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href="#related-articles">相关文章</一个></div> </div> </div> </div> </div> <div class="ant-col ThreeColumnLayout_middleColumn__sbd41"> <div class="ArticleMiddleSection_articleMiddleSection__gAv9z"> <div class="articleHeader"> <strong>研究文章|开放获取</strong> <div class="articleHeader__meta"> <span>体积2011年|</span> <span>文章的ID790721年|</span> <span class="articleHeader__meta_doiLink"><a href="https://doi.org/10.1155/2011/790721" aria-label="Doi-link" target="_blank" rel="noreferrer">https://doi.org/10.1155/2011/790721</一个></span> </div> <div class="simpleShowMore"> <button class="simpleShowMore__button">显示引用</button> </div> <h1 class="articleHeader__title">定量模型有效时间针对肿瘤细胞和Neovasculature</h1><div class="articleHeader__authors"> <span class="articleHeader__authors_author"><strong>m . Kohandel</strong><a href="//www.newsama.com/cdn-cgi/l/email-protection" aria-label="Mail Option"><span role="img" class="anticon"> <svg version="1.0" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em" viewbox="0 0 1401 1101"> <path fill="#6ba439" d="M132.5 2.1C101.4 6 71.1 20.5 48.3 42.4c-22.7 21.7-37.5 48.3-44.6 80l-2.2 10.1v837l2.2 10.1c6.7 30 19.3 53.9 39.8 75.3 23.3 24.3 56.4 40.9 90 45 12.8 1.6 1122.2 1.6 1135 0 38.9-4.8 75.9-25.6 100-56.4 15-19.3 24.2-39 29.8-63.9l2.2-10.1v-837l-2.2-10.1c-7.1-31.8-21.9-58.3-44.6-80.1-20.2-19.2-43.9-31.7-73.6-38.5l-9.6-2.3L705 1.4c-321.9-.1-568.5.2-572.5.7zm1123.4 99.5c1.7.4 3.1 1 3.1 1.4 0 .5-125.6 87.7-279 194L700.9 490.2 422 297C268.5 190.7 143 103.4 143 103c0-.5 1-1.1 2.3-1.3 3.5-.7 1107.1-.8 1110.6-.1zM401 404c164.4 113.8 299.4 207 300 207 .6 0 135.6-93.2 300.1-207 164.5-113.9 299.3-207 299.5-207 .2 0 .4 170.9.4 379.7 0 417.9.5 386-6.1 398.3-6.2 11.6-19 21.4-31.9 24.4-5.8 1.4-67.4 1.6-562 1.6s-556.2-.2-562-1.6c-12.9-3-25.7-12.8-31.9-24.4-6.6-12.3-6.1 19.6-6.1-398.3 0-208.8.2-379.7.5-379.7S236.6 290.1 401 404z"></path> </svg></span></a>,<sup>1、2</sup></span> <span class="articleHeader__authors_author">c . a . Haselwandter,<sup>3、4</sup></span> <span class="articleHeader__authors_author">m . Kardar,<sup>3</sup></span> <span class="articleHeader__authors_author">美国森古普塔,<sup>5</sup></span> <span class="articleHeader__authors_author">和美国Sivaloganathan<sup>1、2</sup></span> </div> <div class="simpleShowMore"> <button class="simpleShowMore__button">显示更多</button> </div> <div class="articleHeader__academicEditor"> <strong>学术编辑器:</strong> <span>内斯特诉托雷斯</span> </div> <div class="articleHeader__timeline"> <div class="articleHeader__timeline_item "> <strong>收到了</strong> <span>2010年7月13日</span> </div> <div class="articleHeader__timeline_item "> <strong>接受</strong> <span>2011年1月09</span> </div> <div class="articleHeader__timeline_item articleHeader__timeline_item_sticky"> <strong>发表</strong> <span>2011年3月08</span> </div> </div> </div> <div class="articleBody"> <div class="xml-content"> <h4 class="header" id="abstract">文摘</h4><p>细胞毒性治疗和抗血管新生药物的结合正成为一个最有前途的战略在恶性肿瘤的治疗。但是,这些治疗的时机和测序似乎发挥重要作用在实现协同的结果。使用数学建模方法,基于实验数据,我们调查的空间和时间针对肿瘤细胞和neovasculature纳米输送系统。我们的模型表明,纳米尺度的实验成功交付系统的捕获关键取决于化疗药物在肿瘤组织内。数值结果还表明,大量进一步改善纳米输送系统的效率可以通过调整的时间瞄准机制。</p><span class="end-abs"></span> <h4 id="introduction">1。介绍</h4><p>肿瘤的增长超出了一个无血管的状态需要扩张的血管网络,实现这一过程通过招聘宿主血管(血管)和/或血管生成。虽然抑制肿瘤血管生成是一个有前途的癌症的治疗和控制方法,目前最近的临床前研究表明,抗血管新生的策略不太可能产生显著提高治疗自己,而是需要与常规治疗结合使用来实现最大利益(<一个href="#B8">1</一个>,<一个href="#B9">2</一个>]。然而,到目前为止,实验研究结合反血管增生和细胞毒性治疗显示不同的结果(<一个href="#B15">3</一个>- - - - - -- - - - - -- - - - - -- - - - - -- - - - - -- - - - - -<一个href="#B14">9</一个>),也许部分原因在于不同的调度和测序这些模式。</p><p>目前,一个主要挑战传统和抗血管新生疗法的成功结合,抗血管新生的政府代理人损害血液流动在肿瘤微环境内,从而防止有效的化学治疗剂的交付。这个困难也必须与新兴肿瘤脉管系统的“正常化”的概念。肿瘤血管网络,起源于异常血管生成与有缺陷的内皮时空上异构,基底膜,和周皮细胞覆盖率和特点是间质高血压、缺氧和酸中毒<一个href="#B9">2</一个>]。虽然高全球血液流动特性的许多肿瘤,肿瘤脉管系统非常不规则<我>效率低下的</我>在提供营养,以及化疗药物、恶性细胞。有人建议(<一个href="#B8">1</一个>,<一个href="#B9">2</一个>某些抗血管新生的明智的政府特工可以结构上和功能上“正常化”异常的肿瘤血管网络,呈现脉管系统更有利于有效的药物靶向肿瘤细胞和营养。这瞬态正常化的特点是更常规的血管形态和基底膜结构,外膜细胞覆盖率,增加和减少缺氧和孔隙流体压力。最近的实验和临床研究表明,VEGF(血管内皮生长因子)信号的封锁,被动地砍掉一些不成熟和漏水的血管肿瘤,并积极重塑剩下的血管,导致一个更规范化网络(<一个href="#B21">10</一个>- - - - - -- - - - - -- - - - - -- - - - - -- - - - - -- - - - - -<一个href="#B23">12</一个>]。更最近,它已经表明,建立血管周的一氧化氮梯度也可能导致肿瘤血管正常化(<一个href="#B11">13</一个>]。</p><p>严重限制利用规范化的血管网络,这样的状态持续只有很短的时间内<一个href="#B23">12</一个>,<一个href="#B6">14</一个>- - - - - -- - - - - -- - - - - -- - - - - -- - - - - -- - - - - -<一个href="#B1">16</一个>]。肿瘤血管正常化的瞬态窗口已经过去之后,肿瘤氧化和减少化疗药物的渗透。随后的缺氧激活低氧诱导因子(HIF-1<我>α</我>,移植许多基因参与血管生成,使肿瘤细胞对化疗药物(<一个href="#B17">17</一个>,<一个href="#B3">18</一个>]。因此,空间和时间肿瘤定位起着至关重要的作用在设计有效的综合治疗策略。</p><p>森古普塔et al。<一个href="#B19">19</一个>)最近设计了一个新颖的交付系统(称为纳米细胞)组成一个纳米级pegylated-lipid信封核纳米涂层。化学治疗剂(阿霉素)是纳米颗粒和共轭反血管增生剂(combretastatin)被困在脂质信封。纳米细胞的渗出液进入肿瘤通过增强的渗透和保留(EPR)效应(<一个href="#B24">20.</一个>,<一个href="#B20">21</一个>)(见图<一个href="//www.newsama.com/journals/cmmm/2011/790721/fig1/" target="_blank">1</一个>),由于肿瘤脉管系统的高度漏水的性质(毛孔的直径400 - 600 nm)。这是图中清晰可见<一个href="//www.newsama.com/journals/cmmm/2011/790721/fig1/" target="_blank">1</一个>优惠累积的纳米细胞(与量子点标记)在肿瘤相比其他vascularised组织:纳米细胞空间限制在正常血管但渗出液从肿瘤脉管系统(<一个href="#B19">19</一个>]。抗血管新生的快速释放剂导致至少部分肿瘤血管网络的崩溃。裹入纳米粒子然后慢慢释放化疗药物,仍局部由于破坏附近的脉管系统。森古普塔et al。<一个href="#B19">19</一个>)相比,连续给药使用纳米细胞的影响与一些传统方法在小鼠B16转椅:F10黑色素瘤或路易斯肺癌癌。动物治疗纳米细胞含有两种药物显示一个更好的比任何其他治疗组肿瘤反应。</p><div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-4ecd010815b72829b895b016e82ba604"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/figures/790721.fig.001.jpg"> <br> <strong></strong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-4ecd010815b72829b895b016e82ba604 partial-carousel-thumbnail"> <button aria-label="Slide to " class="partial-carousel-dot"><img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/thumbnails/790721.fig.001_th.jpg"><br><strong></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-4ecd010815b72829b895b016e82ba604 partial-carousel-next-prev"> <button aria-label="Previous" class="carousel-prev"></button> <button aria-label="Next" class="carousel-next"></button> </div> </div> </div> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">图1</span> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/cmmm/2011/790721/fig1/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>共焦显微图组织横截面从肿瘤的小鼠在注射后24 h imaging-nanocells。老鼠注射纳米细胞标记与半导体纳米晶体(量子点)监控分布及血管渗漏在肿瘤和正常组织。被应用的部分血管性血友病因子(vWF)描绘脉管系统。图像被使用了蔡司LSM510共焦显微镜<svg height="11.2625" id="M1" style="vertical-align:-0.3135pt" version="1.1" viewbox="0 0 63.962502 11.2625" width="63.962502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.2625)"> <g transform="translate(72,-62.99)"> <text transform="matrix(1,0,0,-1,-71.95,63.35)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 5</tspan> <tspan style="font-size: 12.50px; " x="6.2515001" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="12.503" y="0"> 2</tspan> <tspan style="font-size: 12.50px; " x="21.530167" y="0"> ×</tspan> <tspan style="font-size: 12.50px; " x="32.307751" y="0"> 5</tspan> <tspan style="font-size: 12.50px; " x="38.559254" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="44.810753" y="0"> 2</tspan> </text> </g> </g> </svg>像素的分辨率。很兴奋的部分波长488纳米的激光,吸收和发射在FITC (vWF)和罗丹明(QD)波长。发现纳米细胞正常血管内空间限制的重叠(黄色)的红色和绿色信号合并图像但渗出液从肿瘤脉管系统在24小时看到的主要是红色信号(合并)。</td> </tr> </tbody> </table> </div> </div> </div> </div> <p>虽然上述纳米交付方法产生显著改善影响肿瘤控制,还有潜力释放动力学的进一步细化。这让我们适应数学模型(<一个href="#B12">22</一个>],它整合了肿瘤细胞,血管网络,以及它们的相互作用,化疗和抗血管新生疗法的影响实验系统研究了森古普塔等。此模型的细节描述的部分<一个href="#sec2">2</一个>和<一个href="#sec3">3</一个>讨论的机制的协同效应的纳米细胞治疗建议由我们的模型,以及它如何可能进一步改善纳米细胞治疗的效率。</p><h4我d="methods">2。方法</h4><p>为了设计一个高效的细胞毒性和抗血管新生疗法的组合,有必要考虑肿瘤血管的机制和时间响应抗血管新生药物,以及肿瘤的生长之间的耦合,血管网络,和响应细胞毒性药物。我们最近开发了一个数学模型,其中包括肿瘤细胞和血管网络,以及它们的相互作用,并应用研究的结合反血管增生和放射疗法的治疗(<一个href="#B12">22</一个>]。温克勒的实验数据等。<一个href="#B23">12</一个>)被用来估计模型参数并验证其预测。结果表明,抗血管新生疗法的应用,这暂时导致更好的治疗药物,在放射治疗之前,是最有效的方法,与实验结果一致。</p><p>在本文中,我们建立之前的数学模型(<一个href="#B12">22</一个>),包括化疗和纳米细胞的顺序释放动力学的影响。模型在制定我们的指导原则是使最小的假设底层现象学的细胞过程,同时结合实验的基本特征森古普塔et al。<一个href="#B19">19</一个>]。后者的一个关键特性是释放动力学药物的纳米细胞:combretastatin快速释放(12 h内达到显著水平),而阿霉素释放缓慢延长15天(脂质体相比,大约4天)。我们的数学模型包含了这个时间目标概要文件并允许完全控制其他可能的因素增加纳米细胞治疗的有效性,如药物总量的差异给癌细胞。因此,我们可以直接测试和进一步研究颞森古普塔等提出的定位机制。<一个href="#B19">19</一个>]。</p><h5我d="sec2.1">2.1。肿瘤细胞和血管网络</h5><p>肿瘤生长的先前的研究后,我们模型中肿瘤细胞的密度(在位置<svg height="7.1624999" id="M2" style="vertical-align:-0.11285pt;width:8.7250004px;" version="1.1" viewbox="0 0 8.7250004 7.1624999" width="8.7250004" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.1625)"> <g transform="translate(72,-66.27)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>在时间<svg height="9.125" id="M3" style="vertical-align:-0.11285pt;width:5.0124998px;" version="1.1" viewbox="0 0 5.0124998 9.125" width="5.0124998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,9.125)"> <g transform="translate(72,-64.7)"> <text transform="matrix(1,0,0,-1,-71.95,64.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>由时空领域)<svg height="13.45" id="M4" style="vertical-align:-2.21957pt;width:38.299999px;" version="1.1" viewbox="0 0 38.299999 13.45" width="38.299999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.2139912" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="10.37749" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="17.254141" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="22.455387" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="26.368828" y="0"> )</tspan> </text> </g> </g> </svg>根据费雪方程的一种变体(下图)。这部小说方面,我们的方法是类似的介绍<svg height="13.45" id="M5" style="vertical-align:-2.21957pt;width:41.625px;" version="1.1" viewbox="0 0 41.625 13.45" width="41.625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.8771296" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="13.040629" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="19.917278" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="25.118526" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="29.031965" y="0"> )</tspan> </text> </g> </g> </svg>模型血管的密度。这绕过了占血液流动的确切性质,正如前面演示(<一个href="#B12">22</一个>)之间的相互作用增长的关键特性和血液供给可以被进化方程:<span class="equation" id="EEq1.1"> <svg height="72.5625" id="M6" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 72.5625" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,72.5625)"> <g transform="translate(72,-13.95)"> <text transform="matrix(1,0,0,-1,118.12,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.3765302" y="0"> </tspan> </text> <g> <path d="m 118.12,59.47 12.6,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,119.27,47.59)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.3765302" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="16.120001" y="-8.7600002"> =</tspan> <tspan style="font-size: 12.50px; " x="28.147886" y="-8.7600002"> ∇</tspan> </text> <text transform="matrix(1,0,0,-1,156.57,61.35)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,161.44,56.35)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.9896574" y="0"> +</tspan> <tspan style="font-size: 12.50px; " x="20.329878" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="28.63187" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="32.795368" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="41.822536" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="53.162758" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="59.376747" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="66.31591" y="0"> +</tspan> <tspan style="font-size: 12.50px; " x="77.681137" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="77.668633" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,246.16,53.22)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,251.04,56.35)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="10.952628" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="15.116127" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="21.992777" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="27.194025" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="31.107464" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="37.358963" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="43.572956" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="223.08" y="-0.23"> (</tspan> <tspan style="font-size: 12.50px; " x="227.2435" y="-0.23"> 1</tspan> <tspan style="font-size: 12.50px; " x="233.495" y="-0.23"> )</tspan> <tspan style="font-size: 12.50px; " x="-165.25999" y="26.209999"> </tspan> <tspan style="font-size: 12.50px; " x="-158.88347" y="26.209999"> </tspan> </text> <g> <path d="m 85.78,26.01 15.26,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,88.26,14.13)"> <tspan style="font-size: 12.50px; " x="17.450001" y="-8.7600002"> =</tspan> <tspan style="font-size: 12.50px; " x="31.02" y="-11.29"> </tspan> <tspan style="font-size: 12.50px; " x="29.49" y="-8.7600002"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan 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style="font-size: 12.50px; " x="59.93" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="66.894173" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="78.546967" y="0"> +</tspan> <tspan style="font-size: 12.50px; " x="95.951141" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="89.912193" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="96.251213" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,251.83,27.89)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,256.7,20.37)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="7.5700002" y="-2.52"> +</tspan> <tspan style="font-size: 12.50px; " x="18.935226" y="-2.52"> </tspan> <tspan style="font-size: 12.50px; " x="18.922724" y="-2.52"> </tspan> </text> <text transform="matrix(1,0,0,-1,282.67,19.76)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,287.54,22.89)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.2894888" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="12.452988" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="19.329638" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="24.543388" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="28.456827" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="34.708328" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="43.585457" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="186.58" y="-0.23"> (</tspan> <tspan style="font-size: 12.50px; " x="190.7435" y="-0.23"> 2</tspan> <tspan style="font-size: 12.50px; " x="196.995" y="-0.23"> )</tspan> </text> </g> </g> </svg></span>为简单起见,上述方程无量纲形式给出。他们是通过转换对应dimensionful相关方程<svg height="11.85" id="M8" style="vertical-align:-2.29482pt;width:46.112499px;" version="1.1" viewbox="0 0 46.112499 11.85" width="46.112499" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.85)"> <g transform="translate(72,-62.52)"> <text transform="matrix(1,0,0,-1,-71.95,64.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="9.4647713" y="0"> →</tspan> <tspan style="font-size: 12.50px; " x="26.593882" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="32.870388" y="0"> </tspan> </text> </g> </g> </svg>,<svg height="20.4125" id="M9" style="vertical-align:-4.12569pt;width:90.8125px;" version="1.1" viewbox="0 0 90.8125 20.4125" width="90.8125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,20.4125)"> <g transform="translate(72,-55.67)"> <text transform="matrix(1,0,0,-1,-71.95,59.83)"> <tspan style="font-size: 12.50px; " x="29.57" y="0.87"> √</tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="12.427982" y="0"> →</tspan> </text> <g> <path d="m -30.78,70.71 24.51,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,-30.78,59.83)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.2765059" y="0"> /</tspan> <tspan style="font-size: 12.50px; " x="9.7523403" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-11.15,56.71)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-6.27,59.83)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>,<svg height="14.6" id="M10" style="vertical-align:-3.13504pt;width:75px;" version="1.1" viewbox="0 0 75 14.6" width="75" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="11.765323" y="0"> →</tspan> <tspan style="font-size: 12.50px; " x="28.894432" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="35.108425" y="0"> /</tspan> <tspan style="font-size: 12.50px; " x="38.584259" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-27.14,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> l</tspan> <tspan style="font-size: 8.75px; " x="2.4330561" y="0"> 我</tspan> <tspan style="font-size: 8.75px; " x="4.8661122" y="0"> 米</tspan> </text> </g> </g> </svg>(<一个href="#B12">22</一个>),<svg height="9.875" id="M11" style="vertical-align:-2.29482pt;width:7.9749999px;" version="1.1" viewbox="0 0 7.9749999 9.875" width="7.9749999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,9.875)"> <g transform="translate(72,-64.1)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>是净增殖率,<svg height="14.2375" id="M12" style="vertical-align:-3.13504pt;width:18.5625px;" version="1.1" viewbox="0 0 18.5625 14.2375" width="18.5625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.2375)"> <g transform="translate(72,-60.61)"> <text transform="matrix(1,0,0,-1,-71.95,63.79)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.07,60.66)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> </g> </g> </svg>是肿瘤细胞的扩散系数,<svg height="10.925" id="M13" style="vertical-align:-3.13504pt;width:26.75px;" version="1.1" viewbox="0 0 26.75 10.925" width="26.75" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.925)"> <g transform="translate(72,-63.26)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.74,63.31)"> <tspan style="font-size: 8.75px; " x="0" y="0"> l</tspan> <tspan style="font-size: 8.75px; " x="2.4330561" y="0"> 我</tspan> <tspan style="font-size: 8.75px; " x="4.8661122" y="0"> 米</tspan> </text> </g> </g> </svg>是肿瘤细胞的“承载能力”。</p><p>为<svg height="15.75" id="M14" style="vertical-align:-3.13504pt;width:42.237499px;" version="1.1" viewbox="0 0 42.237499 15.75" width="42.237499" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-56.55,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 0</tspan> </text> </g> </g> </svg>,(<一个href="#EEq1.1">1</一个>(无量纲)费雪方程),有两个不动点:一个不稳定的不动点<svg height="11.75" id="M15" style="vertical-align:-0.17555pt;width:41.4375px;" version="1.1" viewbox="0 0 41.4375 11.75" width="41.4375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.75)"> <g transform="translate(72,-62.6)"> <text transform="matrix(1,0,0,-1,-71.95,62.83)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.74,67.83)"> <tspan style="font-size: 8.75px; " x="0" y="0"> ∗</tspan> </text> <text transform="matrix(1,0,0,-1,-57.19,62.83)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 0</tspan> </text> </g> </g> </svg>(没有人口)和一个稳定的不动点<svg height="11.65" id="M16" style="vertical-align:-0.10033pt;width:41.4375px;" version="1.1" viewbox="0 0 41.4375 11.65" width="41.4375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.65)"> <g transform="translate(72,-62.68)"> <text transform="matrix(1,0,0,-1,-71.95,62.83)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.74,67.83)"> <tspan style="font-size: 8.75px; " x="0" y="0"> ∗</tspan> </text> <text transform="matrix(1,0,0,-1,-57.19,62.83)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 1</tspan> </text> </g> </g> </svg>(人口饱和烃承载能力)。没有非线性项的,也就是说,对于简单的指数形式<svg height="15.75" id="M17" style="vertical-align:-3.13504pt;width:42.237499px;" version="1.1" viewbox="0 0 42.237499 15.75" width="42.237499" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-56.55,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 0</tspan> </text> </g> </g> </svg>(1)领导,整合双方,扩散系数为常数,一个简单的指数增加细胞的数量。除了一个无血管的肿瘤的生长状态(最大大小约1 - 2毫米直径)需要血管网络的发展。额外的术语<svg height="15.75" id="M18" style="vertical-align:-3.13504pt;width:33.900002px;" version="1.1" viewbox="0 0 33.900002 15.75" width="33.900002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-60.02,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.8771296" y="0"> </tspan> </text> </g> </g> </svg>(1)表明,肿瘤生长是增强血管的存在。在数学上,这将导致一个稳定的不动点<svg height="15.75" id="M19" style="vertical-align:-3.13504pt;width:91.4375px;" version="1.1" viewbox="0 0 91.4375 15.75" width="91.4375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.95,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.74,67.57)"> <tspan style="font-size: 8.75px; " x="0" y="0"> ∗</tspan> </text> <text transform="matrix(1,0,0,-1,-57.19,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="21.067554" y="0"> +</tspan> <tspan style="font-size: 12.50px; " x="32.432781" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="32.42028" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-17.72,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-12.85,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-3.97,67.57)"> <tspan style="font-size: 8.75px; " x="0" y="0"> ∗</tspan> </text> </g> </g> </svg>;见下面。</p><p>后Kohandel et al。<一个href="#B12">22</一个>)(方程(6)和(8)Kohandel et al。<一个href="#B12">22</一个>)包含交互方面的错误<svg height="14.6" id="M20" style="vertical-align:-3.13504pt;width:64.612503px;" version="1.1" viewbox="0 0 64.612503 14.6" width="64.612503" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-60.02,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="9.5272856" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="13.690785" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="20.567434" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="25.768682" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="29.682121" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="33.845619" y="0"> </tspan> </text> </g> </g> </svg>和<svg height="15.75" id="M21" style="vertical-align:-3.13504pt;width:64.612503px;" version="1.1" viewbox="0 0 64.612503 15.75" width="64.612503" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-60.02,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="9.5272856" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="13.690785" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="20.567434" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="25.768682" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="29.682121" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="33.845619" y="0"> </tspan> </text> </g> </g> </svg>的符号,Kohandel et al。<一个href="#B12">22</一个>),实际上应该读<svg height="14.6" id="M22" style="vertical-align:-3.13504pt;width:63.799999px;" version="1.1" viewbox="0 0 63.799999 14.6" width="63.799999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-60.02,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.8771296" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="13.040629" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="19.917278" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="25.118526" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="29.031965" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="33.195465" y="0"> </tspan> </text> </g> </g> </svg>和<svg height="15.75" id="M23" style="vertical-align:-3.13504pt;width:63.799999px;" version="1.1" viewbox="0 0 63.799999 15.75" width="63.799999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-60.02,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.8771296" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="13.040629" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="19.917278" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="25.118526" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="29.031965" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="33.195465" y="0"> </tspan> </text> </g> </g> </svg>、职责),我们使用(<一个href="#EEq1.1">2</一个>)考虑异构肿瘤脉管系统。这个粗粒度模型,而不是船只的具体模式,产生血管和nonvascular网络。为<svg height="15.75" id="M24" style="vertical-align:-3.13504pt;width:42.237499px;" version="1.1" viewbox="0 0 42.237499 15.75" width="42.237499" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,-56.55,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 0</tspan> </text> </g> </g> </svg>、设置<svg height="12" id="M25" style="vertical-align:-0.17555pt;width:46.849998px;" version="1.1" viewbox="0 0 46.849998 12" width="46.849998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,12)"> <g transform="translate(72,-62.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="10.50252" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="22.530407" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="31.094961" y="0"> 1</tspan> </text> </g> </g> </svg>,<svg height="16.362499" id="M26" style="vertical-align:-2.29482pt;width:36.049999px;" version="1.1" viewbox="0 0 36.049999 16.362499" width="36.049999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,16.3625)"> <g transform="translate(72,-58.91)"> <text transform="matrix(1,0,0,-1,-65.59,63.97)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.3600001" y="2.72"> </tspan> <tspan style="font-size: 12.50px; " x="4.0800052" y="2.72"> =</tspan> <tspan style="font-size: 12.50px; " x="16.120394" y="2.72"> 3</tspan> </text> </g> </g> </svg>,<svg height="13.6125" id="M27" style="vertical-align:-2.34499pt;width:45.974998px;" version="1.1" viewbox="0 0 45.974998 13.6125" width="45.974998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.6125)"> <g transform="translate(72,-61.11)"> <text transform="matrix(1,0,0,-1,-65.9,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.038949" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="3.7634029" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="15.803792" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="24.368347" y="0"> 2</tspan> </text> </g> </g> </svg>,我们得到两个稳定的不动点<svg height="11.65" id="M28" style="vertical-align:-0.10033pt;width:17.5625px;" version="1.1" viewbox="0 0 17.5625 11.65" width="17.5625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.65)"> <g transform="translate(72,-62.68)"> <text transform="matrix(1,0,0,-1,-71.95,62.83)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-63.07,67.83)"> <tspan style="font-size: 8.75px; " x="0" y="0"> ∗</tspan> </text> </g> </g> </svg>在0和1,一个不稳定的一个<svg height="10.9125" id="M29" style="vertical-align:-0.17555pt;width:20.1px;" version="1.1" viewbox="0 0 20.1 10.9125" width="20.1" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.9125)"> <g transform="translate(72,-63.27)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="6.2515001" y="0"> /</tspan> <tspan style="font-size: 12.50px; " x="9.727334" y="0"> 2</tspan> </text> </g> </g> </svg>。从一个随机的(积极的分布式和接近于零)的初始配置<svg height="13.45" id="M30" style="vertical-align:-2.21957pt;width:44.549999px;" version="1.1" viewbox="0 0 44.549999 13.45" width="44.549999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.8771296" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="13.040629" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="19.917278" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="25.118526" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="31.370028" y="0"> )</tspan> </text> </g> </g> </svg>,(<一个href="#EEq1.1">2</一个>)产生的随机分布的岛屿<svg height="10.8125" id="M31" style="vertical-align:-0.10033pt;width:38.424999px;" version="1.1" viewbox="0 0 38.424999 10.8125" width="38.424999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.8125)"> <g transform="translate(72,-63.35)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="12.340461" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="24.38085" y="0"> 1</tspan> </text> </g> </g> </svg>(血管)和<svg height="10.9125" id="M32" style="vertical-align:-0.17555pt;width:38.424999px;" version="1.1" viewbox="0 0 38.424999 10.9125" width="38.424999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.9125)"> <g transform="translate(72,-63.27)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="12.340461" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="24.38085" y="0"> 0</tspan> </text> </g> </g> </svg>(非血管)。最后一项(<一个href="#EEq1.1">2</一个>),<svg height="15.75" id="M33" style="vertical-align:-3.13504pt;width:33.900002px;" version="1.1" viewbox="0 0 33.900002 15.75" width="33.900002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,-60.02,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.2139912" y="0"> </tspan> </text> </g> </g> </svg>,代表着肿瘤细胞对血管的发展的影响。我们假设肿瘤细胞产生proangiogenic细胞因子,导致血管网络的扩展;在现象学的方法中,我们假设更高密度的癌细胞产生更高的血管密度。事实上,一个非零<svg height="15.75" id="M34" style="vertical-align:-3.13504pt;width:15.0375px;" version="1.1" viewbox="0 0 15.0375 15.75" width="15.0375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> </g> </g> </svg>变化稳定的不动点<span class="equation" id="eq1"> <svg height="38.575001" id="M35" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 38.575001" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,38.575)"> <g transform="translate(72,-41.14)"> <text transform="matrix(1,0,0,-1,76.89,53.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,85.76,58.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> ∗</tspan> </text> <text transform="matrix(1,0,0,-1,94.31,53.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="13.24" y="-7.25"> 1</tspan> </text> <g> <path d="m 107.55,56.57 6.25,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,107.55,44.69)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 4</tspan> <tspan style="font-size: 12.50px; " x="9.5299997" y="-1.4299999"> </tspan> <tspan style="font-size: 12.50px; " x="18.9" y="-8.7600002"> 3</tspan> <tspan style="font-size: 12.50px; " x="27.927166" y="-8.7600002"> +</tspan> <tspan style="font-size: 12.50px; " x="39.292393" y="-8.7600002"> </tspan> <tspan style="font-size: 12.50px; " x="39.279888" y="-8.7600002"> </tspan> </text> <text transform="matrix(1,0,0,-1,153.88,50.32)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,158.78,53.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.025006" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,165.8,50.32)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,173.46,53.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ±</tspan> <tspan style="font-size: 12.50px; " x="11.34" y="1.84"> </tspan> </text> <g> <path d="m 198.02,70.6 127.26,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,198.02,53.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 8</tspan> <tspan style="font-size: 12.50px; " x="8.3299999" y="2.52"> </tspan> <tspan style="font-size: 12.50px; " x="14.21" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="14.184994" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,219.26,50.32)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,226.91,53.45)"> <tspan style="font-size: 12.50px; " x="17.59" y="2.52"> </tspan> <tspan style="font-size: 12.50px; " x="26.219999" y="0"> +</tspan> <tspan style="font-size: 12.50px; " x="37.57" y="2.52"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="11.340221" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="43.419998" y="0"> 3</tspan> <tspan style="font-size: 12.50px; " x="52.434662" y="0"> +</tspan> <tspan style="font-size: 12.50px; " x="63.812393" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="63.799889" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,297.75,50.32)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,302.65,53.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,309.68,50.32)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,314.55,50.93)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,320.4,60.98)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,325.28,46.12)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="11.46" y="-7.3299999"> 。</tspan> <tspan style="font-size: 12.50px; " x="148.84" y="-7.3299999"> (</tspan> <tspan style="font-size: 12.50px; " x="153.00349" y="-7.3299999"> 3</tspan> <tspan style="font-size: 12.50px; " x="159.255" y="-7.3299999"> )</tspan> </text> </g> </g> </svg></span></p> <p>例如,对于<svg height="15.75" id="M36" style="vertical-align:-3.13504pt;width:53.962502px;" version="1.1" viewbox="0 0 53.962502 15.75" width="53.962502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-56.55,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.405136" y="0"> 1</tspan> </text> </g> </g> </svg>和<svg height="15.75" id="M37" style="vertical-align:-3.13504pt;width:53.962502px;" version="1.1" viewbox="0 0 53.962502 15.75" width="53.962502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,-56.55,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.405136" y="0"> 9</tspan> </text> </g> </g> </svg>(从符合获得实验数据,查看结果和讨论部分),<svg height="11.75" id="M38" style="vertical-align:-0.17555pt;width:64.300003px;" version="1.1" viewbox="0 0 64.300003 11.75" width="64.300003" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.75)"> <g transform="translate(72,-62.6)"> <text transform="matrix(1,0,0,-1,-71.95,62.83)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-63.07,67.83)"> <tspan style="font-size: 8.75px; " x="0" y="0"> ∗</tspan> </text> <text transform="matrix(1,0,0,-1,-54.52,62.83)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.405136" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="27.656635" y="0"> 2</tspan> </text> </g> </g> </svg>1.97点。因此,定点1移到一个更高的价值,表明肿瘤血管密度高于相应的正常组织。增加穷人的价值也将利用建模交付肿瘤脉管系统的特点,以及抗血管新生疗法的效果;见下文。</p><h5我d="sec2.2">2.2。交付的纳米细胞和脂质体</h5><p>和上面相同的策略之后,我们模型脂质体和纳米细胞浓度的时空变化<svg height="14.7125" id="M39" style="vertical-align:-3.2316pt;width:45.049999px;" version="1.1" viewbox="0 0 45.049999 14.7125" width="45.049999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-63.56,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-60.34,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="11.040149" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="16.241398" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="20.154837" y="0"> )</tspan> </text> </g> </g> </svg>离散指数<svg height="9.9250002" id="M40" style="vertical-align:-0.13794pt;width:4.9875002px;" version="1.1" viewbox="0 0 4.9875002 9.9250002" width="4.9875002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,9.925)"> <g transform="translate(72,-64.06)"> <text transform="matrix(1,0,0,-1,-71.95,64.25)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>标签的药品监督管理局<svg height="13.0125" id="M41" style="vertical-align:-3.2316pt;width:9.0375004px;" version="1.1" viewbox="0 0 9.0375004 13.0125" width="9.0375004" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.0125)"> <g transform="translate(72,-61.59)"> <text transform="matrix(1,0,0,-1,-71.95,64.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-68.04,61.74)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>。纳米颗粒在肿瘤的渗透取决于他们的大小;大纳米颗粒的100海里(这种情况在森古普塔et al . 2007次实验)似乎保持接近脉管系统(<一个href="#B16">23</一个>]。因此,我们假设扩散的脂质体和纳米细胞在肿瘤周围的组织,以及重吸收这些粒子进入血管,可以忽略。该领域的发展<svg height="14.7125" id="M42" style="vertical-align:-3.2316pt;width:45.049999px;" version="1.1" viewbox="0 0 45.049999 14.7125" width="45.049999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-63.56,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-60.34,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="11.040149" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="16.241398" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="20.154837" y="0"> )</tspan> </text> </g> </g> </svg>然后由无量纲方程建模,<span class="equation" id="EEq1.3"> <svg height="48.1875" id="M43" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 48.1875" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,48.1875)"> <g transform="translate(72,-33.45)"> <text transform="matrix(1,0,0,-1,99.39,58.84)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.3765302" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,114.17,55.71)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <g> <path d="m 99.39,52.73 18,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,103.24,40.85)"> <tspan style="font-size: 12.50px; " x="18.82" y="-8.75"> =</tspan> <tspan style="font-size: 12.50px; " x="36.880001" y="-11.48"> ̃</tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.3765302" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="30.85" y="-8.75"> </tspan> <tspan style="font-size: 12.50px; " x="37.139008" y="-8.75"> Γ</tspan> </text> <text transform="matrix(1,0,0,-1,147.72,46.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,153.03,49.61)"> <tspan style="font-size: 12.50px; " x="73.919998" y="9.7399998"> </tspan> <tspan style="font-size: 12.50px; " x="82.18" y="0.0099999998"> −</tspan> <tspan style="font-size: 12.50px; " x="90.739998" y="7.3400002"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="14.315935" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="25.281067" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="29.444565" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="36.321217" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="41.522465" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="45.435902" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="51.687401" y="0"> e</tspan> <tspan style="font-size: 12.50px; " x="57.238735" y="0"> x</tspan> <tspan style="font-size: 12.50px; " x="63.490234" y="0"> p</tspan> <tspan style="font-size: 12.50px; " x="101.32" y="-8.21"> </tspan> <tspan style="font-size: 12.50px; " x="112.27263" y="-8.21"> (</tspan> <tspan style="font-size: 12.50px; " x="116.43613" y="-8.21"> </tspan> <tspan style="font-size: 12.50px; " x="123.31277" y="-8.21"> ,</tspan> <tspan style="font-size: 12.50px; " x="128.52654" y="-8.21"> </tspan> <tspan style="font-size: 12.50px; " x="132.43997" y="-8.21"> )</tspan> </text> <g> <path d="m 254.35,52.73 35.29,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,260.74,40.85)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,269.61,37.72)"> <tspan style="font-size: 8.75px; " x="0" y="0"> l</tspan> <tspan style="font-size: 8.75px; " x="2.4330561" y="0"> 我</tspan> <tspan style="font-size: 8.75px; " x="4.8661122" y="0"> 米</tspan> </text> <text transform="matrix(1,0,0,-1,290.83,42.27)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,300.21,64.82)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,305.08,39.87)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="10.35" y="-9.7299995"> 。</tspan> <tspan style="font-size: 12.50px; " x="169.03999" y="-9.7299995"> (</tspan> <tspan style="font-size: 12.50px; " x="173.20351" y="-9.7299995"> 4</tspan> <tspan style="font-size: 12.50px; " x="179.455" y="-9.7299995"> )</tspan> </text> </g> </g> </svg></span>这个函数<svg height="14.7125" id="M44" style="vertical-align:-3.2316pt;width:28.625px;" version="1.1" viewbox="0 0 28.625 14.7125" width="28.625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> Γ</tspan> </text> <text transform="matrix(1,0,0,-1,-64.61,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.39,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> </text> </g> </g> </svg>代表(平均)浓度的脂质体和纳米细胞在血管中(见部分<一个href="#sec2.4">2.4</一个>)。肿瘤血管结构和功能异常,血管在提供营养和化疗药物是非常低效的。这个可怜的交付可能是由于有缺陷的血管结构,缺乏灌注的肿瘤血管,不一致的流程,和高孔隙流体压力(<一个href="#B10">24</一个>]。然而,有越来越多的证据表明,血管效率可以提高抗血管新生治疗通过“正常化”的过程(<一个href="#B8">1</一个>,<一个href="#B9">2</一个>]。在(<一个href="#EEq1.3">4</一个>),穷人的肿瘤血管是建模的功能<svg height="17.887501" id="M45" style="vertical-align:-3.13504pt;width:127.225px;" version="1.1" viewbox="0 0 127.225 17.887501" width="127.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,17.8875)"> <g transform="translate(72,-57.69)"> <text transform="matrix(1,0,0,-1,-71.95,60.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="13.040629" y="0"> e</tspan> <tspan style="font-size: 12.50px; " x="18.591961" y="0"> x</tspan> <tspan style="font-size: 12.50px; " x="24.84346" y="0"> p</tspan> <tspan style="font-size: 12.50px; " x="35.258461" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="39.421959" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="47.986515" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="52.150013" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="61.027142" y="0"> /</tspan> <tspan style="font-size: 12.50px; " x="64.502975" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,1.44,57.74)"> <tspan style="font-size: 8.75px; " x="0" y="0"> l</tspan> <tspan style="font-size: 8.75px; " x="2.4330561" y="0"> 我</tspan> <tspan style="font-size: 8.75px; " x="4.8661122" y="0"> 米</tspan> </text> <text transform="matrix(1,0,0,-1,16.53,60.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,20.69,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,25.57,60.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ]</tspan> </text> </g> </g> </svg>。为<svg height="21.125" id="M46" style="vertical-align:-3.13504pt;width:71.787498px;" version="1.1" viewbox="0 0 71.787498 21.125" width="71.787498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,21.125)"> <g transform="translate(72,-55.1)"> <text transform="matrix(1,0,0,-1,-71.95,58.27)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-63.07,55.15)"> <tspan style="font-size: 8.75px; " x="0" y="0"> l</tspan> <tspan style="font-size: 8.75px; " x="2.4330561" y="0"> 我</tspan> <tspan style="font-size: 8.75px; " x="4.8661122" y="0"> 米</tspan> </text> <text transform="matrix(1,0,0,-1,-44.51,58.27)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.04" y="-0.69"> √</tspan> </text> <g> <path d="m -20.87,70.71 6.25,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,-20.87,58.27)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 2</tspan> </text> </g> </g> </svg>,这个函数有最大值<svg height="10.8125" id="M47" style="vertical-align:-0.10033pt;width:38.424999px;" version="1.1" viewbox="0 0 38.424999 10.8125" width="38.424999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.8125)"> <g transform="translate(72,-63.35)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="12.340461" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="24.38085" y="0"> 1</tspan> </text> </g> </g> </svg>,对应于有效交付正常的血管。为<svg height="11.0625" id="M48" style="vertical-align:-0.30096pt;width:38.424999px;" version="1.1" viewbox="0 0 38.424999 11.0625" width="38.424999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.0625)"> <g transform="translate(72,-63.15)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="12.340461" y="0"> ></tspan> <tspan style="font-size: 12.50px; " x="24.38085" y="0"> 1</tspan> </text> </g> </g> </svg>对应于肿瘤脉管系统(例如,<svg height="15.75" id="M49" style="vertical-align:-3.13504pt;width:53.962502px;" version="1.1" viewbox="0 0 53.962502 15.75" width="53.962502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-56.55,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.405136" y="0"> 1</tspan> </text> </g> </g> </svg>和<svg height="15.75" id="M50" style="vertical-align:-3.13504pt;width:53.962502px;" version="1.1" viewbox="0 0 53.962502 15.75" width="53.962502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,-56.55,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.405136" y="0"> 9</tspan> </text> </g> </g> </svg>给了<svg height="11.875" id="M51" style="vertical-align:-0.27588pt;width:64.300003px;" version="1.1" viewbox="0 0 64.300003 11.875" width="64.300003" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.875)"> <g transform="translate(72,-62.5)"> <text transform="matrix(1,0,0,-1,-71.95,62.83)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-63.07,67.83)"> <tspan style="font-size: 8.75px; " x="0" y="0"> ∗</tspan> </text> <text transform="matrix(1,0,0,-1,-54.52,62.83)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.405136" y="0"> 9</tspan> <tspan style="font-size: 12.50px; " x="27.656635" y="0"> 7</tspan> </text> </g> </g> </svg>如前一节中所述),减少交付。最后,<svg height="11.0625" id="M52" style="vertical-align:-0.30096pt;width:38.424999px;" version="1.1" viewbox="0 0 38.424999 11.0625" width="38.424999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.0625)"> <g transform="translate(72,-63.15)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="12.340461" y="0"> <</tspan> <tspan style="font-size: 12.50px; " x="24.38085" y="0"> 1</tspan> </text> </g> </g> </svg>对应于不成熟或退化的血管,导致效率低下又营养或药物输送。因此,肿瘤血管,减少<svg height="7.1374998" id="M53" style="vertical-align:-0.10033pt;width:11.225px;" version="1.1" viewbox="0 0 11.225 7.1374998" width="11.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.1375)"> <g transform="translate(72,-66.29)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>值接近1,抗血管新生的管理代理,导致血管效率提高和更好的提供营养和化疗药物(<一个href="#B12">22</一个>]。因此指数项占穷人的脉管系统的交付以及增加脂质体和纳米细胞肿瘤细胞通过规范化。但值得注意的是,强剂量的抗血管新生药物可能导致的价值观<svg height="7.1374998" id="M54" style="vertical-align:-0.10033pt;width:11.225px;" version="1.1" viewbox="0 0 11.225 7.1374998" width="11.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.1375)"> <g transform="translate(72,-66.29)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>小于1,导致可怜的交付通过不成熟的血管或脉管系统的完整回归(<一个href="#B10">24</一个>]。</p><h5我d="sec2.3">2.3。药物释放纳米细胞和脂质体</h5><p>接下来,我们表示<svg height="13.45" id="M55" style="vertical-align:-2.21957pt;width:37.025002px;" version="1.1" viewbox="0 0 37.025002 13.45" width="37.025002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="5.188745" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="9.3522444" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="16.228893" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="21.430141" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="25.34358" y="0"> )</tspan> </text> </g> </g> </svg>和<svg height="13.45" id="M56" style="vertical-align:-2.21957pt;width:38.849998px;" version="1.1" viewbox="0 0 38.849998 13.45" width="38.849998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.6515961" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="10.815095" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="17.691746" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="22.892994" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="26.806433" y="0"> )</tspan> </text> </g> </g> </svg>发布的免费反血管增生和化疗药物的浓度从脂质体和纳米细胞进入肿瘤组织,分别。这些字段的时间和空间演化建模的无量纲方程<span class="equation" id="EEq1.4"> <svg height="72.5625" id="M57" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 72.5625" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,72.5625)"> <g transform="translate(72,-13.95)"> <text transform="matrix(1,0,0,-1,117.56,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.3765302" y="0"> </tspan> </text> <g> <path d="m 117.56,59.47 12.2,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,118.51,47.59)"> <tspan style="font-size: 12.50px; " x="15.92" y="-8.7600002"> =</tspan> <tspan style="font-size: 12.50px; " x="29.49" y="-11.29"> </tspan> <tspan style="font-size: 12.50px; " x="27.959999" y="-8.7600002"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.3765302" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,156.53,53.22)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 3</tspan> </text> <text transform="matrix(1,0,0,-1,161.41,56.35)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ∇</tspan> </text> <text transform="matrix(1,0,0,-1,170.55,61.35)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,175.42,56.35)"> <tspan style="font-size: 12.50px; " x="25.57" y="-2.72"> ̃</tspan> <tspan style="font-size: 12.50px; " x="19.309999" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="7.9644108" y="0"> +</tspan> </text> <text transform="matrix(1,0,0,-1,201.5,63.77)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,213.7,56.35)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,222.95,62.4)"> <tspan style="font-size: 8.75px; " x="0" y="10.24"> </tspan> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,237.23,56.35)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="11.040149" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="16.241398" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="20.154837" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="27.106504" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="44.460667" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="38.459229" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,281.96,61.35)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,294.16,56.35)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="5.188745" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="179.96001" y="-0.23"> (</tspan> <tspan style="font-size: 12.50px; " x="184.1235" y="-0.23"> 5</tspan> <tspan style="font-size: 12.50px; " x="190.375" y="-0.23"> )</tspan> <tspan style="font-size: 12.50px; " x="-213.3" y="26.209999"> </tspan> <tspan style="font-size: 12.50px; " x="-206.91096" y="26.209999"> </tspan> </text> <g> <path d="m 80.86,26.01 13.79,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,82.6,14.13)"> <tspan style="font-size: 12.50px; " x="16.719999" y="-8.7600002"> =</tspan> <tspan style="font-size: 12.50px; " x="30.290001" y="-11.29"> </tspan> <tspan style="font-size: 12.50px; " x="28.76" y="-8.7600002"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.3890328" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,121.42,19.76)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</tspan> </text> <text transform="matrix(1,0,0,-1,126.3,22.89)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ∇</tspan> </text> <text transform="matrix(1,0,0,-1,135.44,27.89)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,140.31,22.89)"> <tspan style="font-size: 12.50px; " x="27.030001" y="-2.72"> ̃</tspan> <tspan style="font-size: 12.50px; " x="20.77" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="9.4272623" y="0"> +</tspan> </text> <text transform="matrix(1,0,0,-1,167.85,30.31)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,181.09,22.89)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,190.34,28.94)"> <tspan style="font-size: 8.75px; " x="0" y="10.24"> </tspan> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,205.67,22.89)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="11.040149" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="16.241398" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="20.154837" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="27.094002" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="38.746796" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="38.446724" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="46.04855" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="57.01368" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="61.177177" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="68.053825" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="73.267578" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="77.181023" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="83.420013" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="92.859779" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="110.21394" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="104.2125" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,316.15,27.89)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,329.39,22.89)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.6515961" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="144.73" y="-0.23"> (</tspan> <tspan style="font-size: 12.50px; " x="148.89349" y="-0.23"> 6</tspan> <tspan style="font-size: 12.50px; " x="155.145" y="-0.23"> )</tspan> </text> </g> </g> </svg></span>我们将对比治疗的四种类型测试实验通过索引<svg height="13.6125" id="M59" style="vertical-align:-2.34499pt;width:41.212502px;" version="1.1" viewbox="0 0 41.212502 13.6125" width="41.212502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.6125)"> <g transform="translate(72,-61.11)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.3269978" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="20.367388" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="24.543388" y="0"> - - - - - -</tspan> <tspan style="font-size: 12.50px; " x="26.63139" y="0"> 4</tspan> </text> </g> </g> </svg>,表示化疗(NC [D],<svg height="13.6125" id="M60" style="vertical-align:-2.34499pt;width:33.412498px;" version="1.1" viewbox="0 0 33.412498 13.6125" width="33.412498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.6125)"> <g transform="translate(72,-61.11)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.3269978" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="20.367388" y="0"> 1</tspan> </text> </g> </g> </svg>),抗血管新生疗法(L [C],<svg height="13.6125" id="M61" style="vertical-align:-2.34499pt;width:33.412498px;" version="1.1" viewbox="0 0 33.412498 13.6125" width="33.412498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.6125)"> <g transform="translate(72,-61.11)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.3269978" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="20.367388" y="0"> 2</tspan> </text> </g> </g> </svg>),简单的脂质体封装(L (CD),<svg height="13.6125" id="M62" style="vertical-align:-2.34499pt;width:33.412498px;" version="1.1" viewbox="0 0 33.412498 13.6125" width="33.412498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.6125)"> <g transform="translate(72,-61.11)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.3269978" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="20.367388" y="0"> 3</tspan> </text> </g> </g> </svg>)和纳米细胞(NC (CD),<svg height="13.6125" id="M63" style="vertical-align:-2.34499pt;width:33.412498px;" version="1.1" viewbox="0 0 33.412498 13.6125" width="33.412498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.6125)"> <g transform="translate(72,-61.11)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.3269978" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="20.367388" y="0"> 4</tspan> </text> </g> </g> </svg>)。免费的抗血管和化疗药物释放纳米细胞和脂质体是小到可以通过肿瘤组织(右边的第一项(<一个href="#EEq1.4">5</一个>)和(<一个href="#EEq1.4">6</一个>);<svg height="19.075001" id="M64" style="vertical-align:-3.25793pt;width:18.799999px;" version="1.1" viewbox="0 0 18.799999 19.075001" width="18.799999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,19.075)"> <g transform="translate(72,-56.74)"> <text transform="matrix(1,0,0,-1,-70.42,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-1.53" y="2.54"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.89,56.91)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 3</tspan> </text> </g> </g> </svg>和<svg height="18.924999" id="M65" style="vertical-align:-3.13504pt;width:18.799999px;" version="1.1" viewbox="0 0 18.799999 18.924999" width="18.799999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,18.925)"> <g transform="translate(72,-56.86)"> <text transform="matrix(1,0,0,-1,-70.42,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-1.53" y="2.54"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.89,56.91)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</tspan> </text> </g> </g> </svg>是无量纲扩散系数)。这个词<svg height="14.7125" id="M66" style="vertical-align:-2.29482pt;width:71.099998px;" version="1.1" viewbox="0 0 71.099998 14.7125" width="71.099998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.95,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="8.8646269" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.5645552" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="16.16638" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="25.043509" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="29.207008" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="36.083656" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="41.297409" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="45.21085" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="49.374348" y="0"> </tspan> </text> </g> </g> </svg>描述了免费的再吸收化疗药物进入血管。我们假设没有这样的术语出现在方程<svg height="13.45" id="M67" style="vertical-align:-2.21957pt;width:37.025002px;" version="1.1" viewbox="0 0 37.025002 13.45" width="37.025002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="5.188745" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="9.3522444" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="16.228893" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="21.430141" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="25.34358" y="0"> )</tspan> </text> </g> </g> </svg>从抗血管新生药物作用于正常以及异常血管,防止吸收。然而,两个方程涉及的表单<svg height="13.9375" id="M68" style="vertical-align:-0.17555pt;width:41.1875px;" version="1.1" viewbox="0 0 41.1875 13.9375" width="41.1875" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.9375)"> <g transform="translate(72,-60.85)"> <text transform="matrix(1,0,0,-1,-71.95,61.03)"> <tspan style="font-size: 12.50px; " x="0" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="14.565995" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="8.5645552" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-57.11,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,-44.91,61.03)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>和<svg height="13.9625" id="M69" style="vertical-align:-0.17555pt;width:44.474998px;" version="1.1" viewbox="0 0 44.474998 13.9625" width="44.474998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.9625)"> <g transform="translate(72,-60.83)"> <text transform="matrix(1,0,0,-1,-71.95,61.03)"> <tspan style="font-size: 12.50px; " x="0" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="14.565995" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="8.5645552" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-57.11,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,-43.87,61.03)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>,这描述的自然衰变免费药物。自由的释放化疗和抗血管药物(<一个href="#EEq1.4">5</一个>)和(<一个href="#EEq1.4">6</一个>),也就是说,<svg height="24.075001" id="M70" style="vertical-align:-5.84473pt;width:73.400002px;" version="1.1" viewbox="0 0 73.400002 24.075001" width="73.400002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,24.075)"> <g transform="translate(72,-52.74)"> <text transform="matrix(1,0,0,-1,-65.69,61.34)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.2600002" y="2.73"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.19,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> ,</tspan> <tspan style="font-size: 8.75px; " x="10.975008" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="17.889088" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,-43.88,58.61)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-34.63,64.66)"> <tspan style="font-size: 8.75px; " x="0" y="10.24"> </tspan> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> ,</tspan> <tspan style="font-size: 8.75px; " x="10.975008" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="17.889088" y="0"> )</tspan> </text> </g> </g> </svg>,收益<span class="equation" id="EEq2"> <svg height="23.450001" id="M71" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 23.450001" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,23.45)"> <g transform="translate(72,-53.24)"> <text transform="matrix(1,0,0,-1,114.33,59.76)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,123.58,65.81)"> <tspan style="font-size: 8.75px; " x="0" y="10.24"> </tspan> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> ,</tspan> <tspan style="font-size: 8.75px; " x="10.975008" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="17.889088" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,146.97,59.77)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="39.830002" y="6.5599999"> </tspan> <tspan style="font-size: 12.50px; " x="4.1599998" y="0.0099999998"> </tspan> <tspan style="font-size: 12.50px; " x="11.03665" y="0.0099999998"> ,</tspan> <tspan style="font-size: 12.50px; " x="16.237898" y="0.0099999998"> </tspan> <tspan style="font-size: 12.50px; " x="20.151337" y="0.0099999998"> )</tspan> <tspan style="font-size: 12.50px; " x="27.79067" y="0.0099999998"> =</tspan> </text> <text transform="matrix(1,0,0,-1,202.96,53.38)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,206.18,59.76)"> <tspan style="font-size: 12.50px; " x="0" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="8.3395014" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,221.48,65.81)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> ,</tspan> <tspan style="font-size: 8.75px; " x="10.975008" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="17.889088" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.24"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.24"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.24"> </tspan> </text> <text transform="matrix(1,0,0,-1,244.87,59.77)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1599998" y="0.0099999998"> </tspan> <tspan style="font-size: 12.50px; " x="8.0734386" y="0.0099999998"> )</tspan> <tspan style="font-size: 12.50px; " x="14.312436" y="0.0099999998"> </tspan> </text> <text transform="matrix(1,0,0,-1,267.58,56.63)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,272.89,59.77)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1599998" y="0.0099999998"> </tspan> <tspan style="font-size: 12.50px; " x="11.03665" y="0.0099999998"> ,</tspan> <tspan style="font-size: 12.50px; " x="16.237898" y="0.0099999998"> </tspan> <tspan style="font-size: 12.50px; " x="20.151337" y="0.0099999998"> )</tspan> <tspan style="font-size: 12.50px; " x="26.402838" y="0.0099999998"> ,</tspan> <tspan style="font-size: 12.50px; " x="201.23" y="0.0099999998"> (</tspan> <tspan style="font-size: 12.50px; " x="205.39349" y="0.0099999998"> 7</tspan> <tspan style="font-size: 12.50px; " x="211.645" y="0.0099999998"> )</tspan> </text> </g> </g> </svg></span>和所有政府中运行<svg height="13.0125" id="M72" style="vertical-align:-3.2316pt;width:9.0375004px;" version="1.1" viewbox="0 0 9.0375004 13.0125" width="9.0375004" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.0125)"> <g transform="translate(72,-61.59)"> <text transform="matrix(1,0,0,-1,-71.95,64.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-68.04,61.74)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>。发布概要文件<svg height="22.362499" id="M73" style="vertical-align:-5.84473pt;width:61.1875px;" version="1.1" viewbox="0 0 61.1875 22.362499" width="61.1875" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,22.3625)"> <g transform="translate(72,-54.11)"> <text transform="matrix(1,0,0,-1,-71.95,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="8.3395014" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,-56.65,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> ,</tspan> <tspan style="font-size: 8.75px; " x="10.975008" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="17.889088" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.24"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.24"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.24"> </tspan> </text> <text transform="matrix(1,0,0,-1,-35.34,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> </text> </g> </g> </svg>要么是相同的零个或满足<span class="equation" id="eq2"> <svg height="38.387501" id="M74" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 38.387501" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,38.3875)"> <g transform="translate(72,-41.29)"> <text transform="matrix(1,0,0,-1,144.89,46.41)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,161.05,46.58)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,166.35,45.26)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,173.35,66.99)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,176.09,64.8)"> <tspan style="font-size: 6.25px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,172.1,41.46)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 0</tspan> </text> <text transform="matrix(1,0,0,-1,183.39,52.96)"> <tspan style="font-size: 12.50px; " x="0" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="8.3395014" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,198.7,59.01)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> ,</tspan> <tspan style="font-size: 8.75px; " x="10.975008" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="17.889088" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.24"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.24"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.24"> </tspan> </text> <text transform="matrix(1,0,0,-1,222.08,52.97)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1599998" y="0.0099999998"> </tspan> <tspan style="font-size: 12.50px; " x="8.0734386" y="0.0099999998"> )</tspan> <tspan style="font-size: 12.50px; " x="14.324939" y="0.0099999998"> </tspan> <tspan style="font-size: 12.50px; " x="20.976536" y="0.0099999998"> </tspan> <tspan style="font-size: 12.50px; " x="28.353306" y="0.0099999998"> =</tspan> <tspan style="font-size: 12.50px; " x="40.393696" y="0.0099999998"> 1</tspan> <tspan style="font-size: 12.50px; " x="46.645195" y="0.0099999998"> ,</tspan> <tspan style="font-size: 12.50px; " x="252.03999" y="0.0099999998"> (</tspan> <tspan style="font-size: 12.50px; " x="256.20349" y="0.0099999998"> 8</tspan> <tspan style="font-size: 12.50px; " x="262.45499" y="0.0099999998"> )</tspan> </text> </g> </g> </svg></span>如上所述,在所有管理时间和运行总和<svg height="16.637501" id="M75" style="vertical-align:-4.77652pt;width:48.037498px;" version="1.1" viewbox="0 0 48.037498 16.637501" width="48.037498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,16.6375)"> <g transform="translate(72,-58.69)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-68.04,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-58.16,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 7</tspan> </text> </g> </g> </svg>天是最长的时间考虑森古普塔的实验等。<一个href="#B19">19</一个>]。上述条件发布概要文件修复药物释放脂质体和纳米细胞的总量超过的时间间隔在实验中考虑森古普塔et al。<一个href="#B19">19</一个>),从而确保公平的比较不同的治疗策略在我们的模型中。</p><p>最后,化疗和抗血管新生疗法对癌症细胞的影响和血管进行建模<span class="equation" id="EEq3"> <svg height="77.150002" id="M76" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 77.150002" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,77.15)"> <g transform="translate(72,-10.28)"> <text transform="matrix(1,0,0,-1,90.12,63.49)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.3890328" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="14.678522" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="18.842022" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="25.718672" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="30.932423" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="34.84586" y="0"> )</tspan> </text> <g> <path d="m 90.12,58.4 39.01,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,104.48,46.52)"> <tspan style="font-size: 12.50px; " x="25.85" y="-15.67"> |</tspan> <tspan style="font-size: 12.50px; " x="25.85" y="-5.0100002"> |</tspan> <tspan style="font-size: 12.50px; " x="25.85" y="-1.84"> |</tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.3765302" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,132.83,45.71)"> <tspan style="font-size: 8.75px; " x="0" y="0"> c</tspan> <tspan style="font-size: 8.75px; " x="3.7546079" y="0"> h</tspan> <tspan style="font-size: 8.75px; " x="8.1306076" y="0"> e</tspan> <tspan style="font-size: 8.75px; " x="12.016496" y="0"> 米</tspan> <tspan style="font-size: 8.75px; " x="18.825552" y="0"> o</tspan> </text> <text transform="matrix(1,0,0,-1,159.99,55.27)"> <tspan style="font-size: 12.50px; " x="23.48" y="-2.71"> </tspan> <tspan style="font-size: 12.50px; " x="20.610001" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.040389" y="0"> −</tspan> </text> <text transform="matrix(1,0,0,-1,189.56,64.08)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,202.8,55.27)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="9.4772739" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="13.640773" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="20.517424" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="25.731174" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="29.644613" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="35.896114" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="42.110104" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="57.276241" y="0"> f</tspan> <tspan style="font-size: 12.50px; " x="61.052151" y="0"> o</tspan> <tspan style="font-size: 12.50px; " x="67.30365" y="0"> r</tspan> <tspan style="font-size: 12.50px; " x="75.630646" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="83.957642" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="95.998032" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="102.24953" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="107.46329" y="0"> 3</tspan> <tspan style="font-size: 12.50px; " x="113.71478" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="118.91603" y="0"> 4</tspan> <tspan style="font-size: 12.50px; " x="125.16753" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="-109" y="27.07"> </tspan> <tspan style="font-size: 12.50px; " x="-102.61097" y="27.07"> </tspan> <tspan style="font-size: 12.50px; " x="-91.645836" y="27.07"> (</tspan> <tspan style="font-size: 12.50px; " x="-87.482338" y="27.07"> </tspan> <tspan style="font-size: 12.50px; " x="-80.60569" y="27.07"> ,</tspan> <tspan style="font-size: 12.50px; " x="-75.404442" y="27.07"> </tspan> <tspan style="font-size: 12.50px; " x="-71.490997" y="27.07"> )</tspan> </text> <g> <path d="m 93.8,23.11 41.68,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,109.49,11.23)"> <tspan style="font-size: 12.50px; " x="27.190001" y="-15.67"> |</tspan> <tspan style="font-size: 12.50px; " x="27.190001" y="-5"> |</tspan> <tspan style="font-size: 12.50px; " x="27.190001" y="-1.84"> |</tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.3890328" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,139.18,10.42)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 一个</tspan> <tspan style="font-size: 8.75px; " x="3.8858881" y="0"> n</tspan> <tspan style="font-size: 8.75px; " x="8.2618876" y="0"> t</tspan> <tspan style="font-size: 8.75px; " x="10.694944" y="0"> 我</tspan> </text> <text transform="matrix(1,0,0,-1,156.28,19.98)"> <tspan style="font-size: 12.50px; " x="23.469999" y="-2.71"> </tspan> <tspan style="font-size: 12.50px; " x="20.6" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> −</tspan> </text> <text transform="matrix(1,0,0,-1,185.84,28.79)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,198.04,19.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="7.8893929" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="12.052892" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="18.929543" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="24.143293" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="28.056732" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="34.308231" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="43.185364" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="58.351501" y="0"> f</tspan> <tspan style="font-size: 12.50px; " x="62.127407" y="0"> o</tspan> <tspan style="font-size: 12.50px; " x="68.378906" y="0"> r</tspan> <tspan style="font-size: 12.50px; " x="76.705902" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="85.032906" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="97.073296" y="0"> 2</tspan> <tspan style="font-size: 12.50px; " x="103.32479" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="108.53854" y="0"> 3</tspan> <tspan style="font-size: 12.50px; " x="114.79005" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="119.99129" y="0"> 4</tspan> <tspan style="font-size: 12.50px; " x="126.25529" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="276.07999" y="-18.040001"> (</tspan> <tspan style="font-size: 12.50px; " x="280.2435" y="-18.040001"> 9</tspan> <tspan style="font-size: 12.50px; " x="286.495" y="-18.040001"> )</tspan> </text> </g> </g> </svg></span>的竖线表明上述条款添加到(<一个href="#EEq1.1">1</一个>)和(<一个href="#EEq1.1">2</一个>),分别。在这里,<svg height="18.525" id="M77" style="vertical-align:-0.17555pt;width:27.887501px;" version="1.1" viewbox="0 0 27.887501 18.525" width="27.887501" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,18.525)"> <g transform="translate(72,-57.18)"> <text transform="matrix(1,0,0,-1,-69.07,59.94)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-2.8800001" y="2.71"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.99,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> </g> </g> </svg>和<svg height="18.525" id="M78" style="vertical-align:-0.17555pt;width:26.575001px;" version="1.1" viewbox="0 0 26.575001 18.525" width="26.575001" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,18.525)"> <g transform="translate(72,-57.18)"> <text transform="matrix(1,0,0,-1,-69.07,59.94)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-2.8800001" y="2.71"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.99,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> </g> </g> </svg>分别代表化疗和抗血管新生疗法的力量;<svg height="13.45" id="M79" style="vertical-align:-2.21957pt;width:38.849998px;" version="1.1" viewbox="0 0 38.849998 13.45" width="38.849998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.6515961" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="10.815095" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="17.691746" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="22.892994" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="26.806433" y="0"> )</tspan> </text> </g> </g> </svg>和<svg height="13.45" id="M80" style="vertical-align:-2.21957pt;width:37.025002px;" version="1.1" viewbox="0 0 37.025002 13.45" width="37.025002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="5.188745" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="9.3522444" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="16.228893" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="21.430141" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="25.34358" y="0"> )</tspan> </text> </g> </g> </svg>是由(<一个href="#EEq1.4">5</一个>)和(<一个href="#EEq1.4">6</一个>)。上面的模型及其参数化的细节将在下面讨论。</p><h5我d="sec2.4">2.4。发布概要文件</h5><p>确定发布概要文件,<svg height="22.362499" id="M81" style="vertical-align:-5.84473pt;width:61.1875px;" version="1.1" viewbox="0 0 61.1875 22.362499" width="61.1875" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,22.3625)"> <g transform="translate(72,-54.11)"> <text transform="matrix(1,0,0,-1,-71.95,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="8.3395014" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,-56.65,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> ,</tspan> <tspan style="font-size: 8.75px; " x="10.975008" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="17.889088" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.24"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.24"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.24"> </tspan> </text> <text transform="matrix(1,0,0,-1,-35.34,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> </text> </g> </g> </svg>为<svg height="13.6125" id="M82" style="vertical-align:-2.34499pt;width:41.212502px;" version="1.1" viewbox="0 0 41.212502 13.6125" width="41.212502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.6125)"> <g transform="translate(72,-61.11)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.3269978" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="20.367388" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="24.543388" y="0"> - - - - - -</tspan> <tspan style="font-size: 12.50px; " x="26.63139" y="0"> 4</tspan> </text> </g> </g> </svg>,我们首先注意到数控[D]只涉及化疗(但不包含抗血管新生疗法);因此,<svg height="22.525" id="M83" style="vertical-align:-5.9676pt;width:77.012497px;" version="1.1" viewbox="0 0 77.012497 22.525" width="77.012497" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,22.525)"> <g transform="translate(72,-53.98)"> <text transform="matrix(1,0,0,-1,-71.95,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="8.3395014" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,-56.65,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.76"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.76"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.76"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-44.45,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="15.716271" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="27.744158" y="0"> 0</tspan> </text> </g> </g> </svg>;回想一下,用数控[D]<svg height="13.6125" id="M84" style="vertical-align:-2.34499pt;width:33.412498px;" version="1.1" viewbox="0 0 33.412498 13.6125" width="33.412498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.6125)"> <g transform="translate(72,-61.11)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.3269978" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="20.367388" y="0"> 1</tspan> </text> </g> </g> </svg>。同样的,<svg height="22.525" id="M85" style="vertical-align:-5.9676pt;width:78.3125px;" version="1.1" viewbox="0 0 78.3125 22.525" width="78.3125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,22.525)"> <g transform="translate(72,-53.98)"> <text transform="matrix(1,0,0,-1,-71.95,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="8.3395014" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,-56.65,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.76"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.76"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.76"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,-43.41,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="15.716271" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="27.744158" y="0"> 0</tspan> </text> </g> </g> </svg>因为L [C] (<svg height="13.6125" id="M86" style="vertical-align:-2.34499pt;width:33.412498px;" version="1.1" viewbox="0 0 33.412498 13.6125" width="33.412498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.6125)"> <g transform="translate(72,-61.11)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.3269978" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="20.367388" y="0"> 2</tspan> </text> </g> </g> </svg>)只涉及抗血管新生疗法。剩下的发布概要文件应该是固定的<我>在活的有机体内</我>释放实验。我们预计发布概要文件combretastatin和阿霉素的L (CD)类似于L combretastatin发布概要文件的[C],<svg height="22.525" id="M87" style="vertical-align:-5.9676pt;width:189.25px;" version="1.1" viewbox="0 0 189.25 22.525" width="189.25" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,22.525)"> <g transform="translate(72,-53.98)"> <text transform="matrix(1,0,0,-1,-71.95,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="8.3395014" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,-56.65,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.76"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.76"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.76"> 3</tspan> </text> <text transform="matrix(1,0,0,-1,-44.45,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="15.716271" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="27.744158" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="36.083656" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,-1.39,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.76"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.76"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.76"> 3</tspan> </text> <text transform="matrix(1,0,0,-1,11.85,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="15.703768" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="27.744158" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="36.083656" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,54.9,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.76"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.76"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.76"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,67.1,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> </text> </g> </g> </svg>这是由于这一事实对所有这些情况下,包含在脂质体的药物。同样的,因为所有的纳米细胞(独立于他们是否包含combretastatin)脂质体在外层,<svg height="22.525" id="M88" style="vertical-align:-5.9676pt;width:121.475px;" version="1.1" viewbox="0 0 121.475 22.525" width="121.475" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,22.525)"> <g transform="translate(72,-53.98)"> <text transform="matrix(1,0,0,-1,-71.95,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="8.3395014" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,-56.65,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.76"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.76"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.76"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-43.41,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="15.716271" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="27.744158" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="36.083656" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,-0.35,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.76"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.76"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.76"> 4</tspan> </text> <text transform="matrix(1,0,0,-1,12.89,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> </text> </g> </g> </svg>。因此,我们需要确定功能<svg height="22.525" id="M89" style="vertical-align:-5.9676pt;width:51.112499px;" version="1.1" viewbox="0 0 51.112499 22.525" width="51.112499" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,22.525)"> <g transform="translate(72,-53.98)"> <text transform="matrix(1,0,0,-1,-71.95,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="8.3395014" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,-56.65,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.76"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.76"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.76"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-43.41,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> </text> </g> </g> </svg>,<svg height="22.525" id="M90" style="vertical-align:-5.9676pt;width:49.799999px;" version="1.1" viewbox="0 0 49.799999 22.525" width="49.799999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,22.525)"> <g transform="translate(72,-53.98)"> <text transform="matrix(1,0,0,-1,-71.95,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="8.3395014" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,-56.65,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.76"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.76"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.76"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,-44.45,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> </text> </g> </g> </svg>,<svg height="22.525" id="M91" style="vertical-align:-5.9676pt;width:49.799999px;" version="1.1" viewbox="0 0 49.799999 22.525" width="49.799999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,22.525)"> <g transform="translate(72,-53.98)"> <text transform="matrix(1,0,0,-1,-71.95,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="8.3395014" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,-56.65,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.76"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.76"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.76"> 4</tspan> </text> <text transform="matrix(1,0,0,-1,-44.45,59.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> </text> </g> </g> </svg>。的<我>在体外</我>森古普塔等的研究。<一个href="#B19">19</一个>]表明,从数控[D]阿霉素的释放是延迟相对于combretastatin从脂质体的释放,以延长时间大约4天的脂质体和延长时间大约15天的纳米细胞的核心。在此基础上我们<span class="equation" id="EEq4"> <svg height="166.71249" id="M92" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 166.71249" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,166.7125)"> <g transform="translate(72,61.37)"> <text transform="matrix(1,0,0,-1,73.32,49.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> R</tspan> <tspan style="font-size: 12.50px; " x="8.3395014" y="0"> P</tspan> </text> <text transform="matrix(1,0,0,-1,88.63,55.65)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.77"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.77"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.77"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,103.95,49.61)"> <tspan style="font-size: 12.50px; " x="33.580002" y="-7.2399998"> 1</tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="15.703768" y="0"> =</tspan> </text> <g> <path d="m 132.9,52.73 15.51,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,132.9,40.85)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,143.54,37.72)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,149.61,49.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.6300001" y="2.51"> </tspan> <tspan style="font-size: 12.50px; " x="14.48" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="21.169106" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="32.509327" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,186.04,46.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,189.26,47.09)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="7.9269018" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="13.79" y="-2.51"> </tspan> <tspan style="font-size: 12.50px; " x="20.479105" y="-2.51"> −</tspan> <tspan style="font-size: 12.50px; " x="31.819326" y="-2.51"> </tspan> </text> <text transform="matrix(1,0,0,-1,225,46.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,228.22,47.09)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,234.07,57.13)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,238.35,54.95)"> <tspan style="font-size: 6.25px; " x="0" y="0"> N</tspan> <tspan style="font-size: 6.25px; " x="4.4514241" y="0"> C</tspan> </text> <text transform="matrix(1,0,0,-1,250.05,49.6)"> <tspan style="font-size: 12.50px; " x="22.219999" y="9.7299995"> </tspan> <tspan style="font-size: 12.50px; " x="32.32" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="42.080002" y="-8.0699997"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> e</tspan> <tspan style="font-size: 12.50px; " x="5.551332" y="0"> x</tspan> <tspan style="font-size: 12.50px; " x="11.802832" y="0"> p</tspan> <tspan style="font-size: 12.50px; " x="47.939999" y="-10.58"> </tspan> <tspan style="font-size: 12.50px; " x="54.616604" y="-10.58"> −</tspan> <tspan style="font-size: 12.50px; " x="65.969322" y="-10.58"> </tspan> </text> <text transform="matrix(1,0,0,-1,319.93,57.05)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,323.15,57.67)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <g> <path d="m 292.13,52.73 36.88,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,301.09,40.85)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,307.49,37.72)"> <tspan style="font-size: 8.75px; " x="0" y="0"> N</tspan> <tspan style="font-size: 8.75px; " x="6.2314239" y="0"> C</tspan> </text> <text transform="matrix(1,0,0,-1,330.2,39.87)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="12.19" y="-9.7299995"> ,</tspan> <tspan style="font-size: 12.50px; " x="-254.25999" y="37.68"> R</tspan> <tspan style="font-size: 12.50px; " x="-245.9205" y="37.68"> P</tspan> </text> <text transform="matrix(1,0,0,-1,91.24,8.24)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.77"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.77"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.77"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,105.53,2.19)"> <tspan style="font-size: 12.50px; " x="33.580002" y="-7.25"> 1</tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="15.703768" y="0"> =</tspan> </text> <g> <path d="m 134.47,5.31 15.52,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,134.47,-6.56)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,145.11,-9.69)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,151.18,2.19)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.6400003" y="2.52"> </tspan> <tspan style="font-size: 12.50px; " x="14.49" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="21.179106" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="32.519325" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,187.62,-0.94)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,190.84,-0.33)"> <tspan style="font-size: 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<text transform="matrix(1,0,0,-1,307.81,-9.69)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,327.58,-7.55)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="12.19" y="-9.7399998"> ,</tspan> <tspan style="font-size: 12.50px; " x="-251.64" y="37.68"> R</tspan> <tspan style="font-size: 12.50px; " x="-243.30051" y="37.68"> P</tspan> </text> <text transform="matrix(1,0,0,-1,91.24,-39.18)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> <tspan style="font-size: 8.75px; " x="0" y="10.76"> </tspan> <tspan style="font-size: 8.75px; " x="2.7218721" y="10.76"> ,</tspan> <tspan style="font-size: 8.75px; " x="4.9098721" y="10.76"> 4</tspan> </text> <text transform="matrix(1,0,0,-1,105.53,-45.22)"> <tspan style="font-size: 12.50px; " x="33.580002" y="-7.25"> 1</tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="15.703768" y="0"> =</tspan> </text> <g> <path d="m 134.47,-42.1 15.52,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,134.47,-53.98)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,145.11,-57.1)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</tspan> </text> <text transform="matrix(1,0,0,-1,151.18,-45.23)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.6400003" y="2.51"> </tspan> <tspan style="font-size: 12.50px; " x="14.49" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="21.179106" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="32.519325" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,187.62,-48.35)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,190.84,-47.74)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="7.9269018" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="13.79" y="-2.51"> </tspan> <tspan style="font-size: 12.50px; " x="20.466602" y="-2.51"> −</tspan> <tspan style="font-size: 12.50px; " x="31.819326" y="-2.51"> </tspan> </text> <text transform="matrix(1,0,0,-1,226.57,-48.35)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,229.79,-47.74)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,235.65,-37.69)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,239.93,-34.19)"> <tspan style="font-size: 6.25px; " x="0" y="0"> ′</tspan> <tspan style="font-size: 6.25px; " x="0" y="6.3899999"> </tspan> </text> <text transform="matrix(1,0,0,-1,247.43,-45.23)"> <tspan style="font-size: 12.50px; " x="22.219999" y="9.7299995"> </tspan> <tspan style="font-size: 12.50px; " x="32.330002" y="0"> −</tspan> <tspan style="font-size: 12.50px; " x="42.09" y="-8.0699997"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> e</tspan> <tspan style="font-size: 12.50px; " x="5.551332" y="0"> x</tspan> <tspan style="font-size: 12.50px; " x="11.802832" y="0"> p</tspan> <tspan style="font-size: 12.50px; " x="47.939999" y="-10.58"> </tspan> <tspan style="font-size: 12.50px; " x="54.629105" y="-10.58"> −</tspan> <tspan style="font-size: 12.50px; " x="65.969322" y="-10.58"> </tspan> </text> <text transform="matrix(1,0,0,-1,317.32,-37.77)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,320.54,-37.16)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <g> <path d="m 289.52,-42.1 36.87,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,301.4,-54.43)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,307.81,-49.93)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="0" y="9.0200005"> </tspan> </text> <text transform="matrix(1,0,0,-1,327.58,-54.96)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="12.19" y="-9.7299995"> ,</tspan> <tspan style="font-size: 12.50px; " x="140.28999" y="-57.150002"> (</tspan> <tspan style="font-size: 12.50px; " x="144.45351" y="-57.150002"> 1</tspan> <tspan style="font-size: 12.50px; " x="150.705" y="-57.150002"> 0</tspan> <tspan style="font-size: 12.50px; " x="156.9565" y="-57.150002"> )</tspan> </text> </g> </g> </svg></span>在哪里<svg height="14.8375" id="M93" style="vertical-align:-3.2316pt;width:124.8125px;" version="1.1" viewbox="0 0 124.8125 14.8375" width="124.8125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.8375)"> <g transform="translate(72,-60.13)"> <text transform="matrix(1,0,0,-1,-71.95,63.4)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-68.04,60.27)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.34,63.4)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 8</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="23.493137" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="29.744637" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="35.996136" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="41.197384" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="47.448887" y="0"> 2</tspan> <tspan style="font-size: 12.50px; " x="53.700386" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="58.914135" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="65.165634" y="0"> 4</tspan> <tspan style="font-size: 12.50px; " x="71.417137" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="76.63089" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="82.882385" y="0"> 6</tspan> </text> </g> </g> </svg>天是奥巴马政府时期的实验中使用森古普塔et al。<一个href="#B19">19</一个>),常数<svg height="15.775" id="M94" style="vertical-align:-4.37273pt;width:35.924999px;" version="1.1" viewbox="0 0 35.924999 15.775" width="35.924999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.775)"> <g transform="translate(72,-59.38)"> <text transform="matrix(1,0,0,-1,-71.95,63.79)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.31,60.66)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> <tspan style="font-size: 8.75px; " x="4.3759999" y="0"> ,</tspan> <tspan style="font-size: 8.75px; " x="6.5640001" y="0"> 2</tspan> <tspan style="font-size: 8.75px; " x="10.94" y="0"> ,</tspan> <tspan style="font-size: 8.75px; " x="13.128" y="0"> 4</tspan> </text> </g> </g> </svg>确定的归一化条件下,看到(<一个href="#EEq2">7</一个>),<svg height="13.45" id="M95" style="vertical-align:-2.21957pt;width:27.325001px;" version="1.1" viewbox="0 0 27.325001 13.45" width="27.325001" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.5390692" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="10.702568" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="17.579218" y="0"> )</tspan> </text> </g> </g> </svg>是单位阶跃函数(定义为<svg height="13.45" id="M96" style="vertical-align:-2.21957pt;width:54.525002px;" version="1.1" viewbox="0 0 54.525002 13.45" width="54.525002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.5390692" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="10.702568" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="17.579218" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="25.218552" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="37.258942" y="0"> 1</tspan> </text> </g> </g> </svg>为<svg height="12.3" id="M97" style="vertical-align:-1.29163pt;width:35.924999px;" version="1.1" viewbox="0 0 35.924999 12.3" width="35.924999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,12.3)"> <g transform="translate(72,-62.16)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="10.339981" y="0"> ≥</tspan> <tspan style="font-size: 12.50px; " x="22.380369" y="0"> 1</tspan> </text> </g> </g> </svg>和<svg height="13.45" id="M98" style="vertical-align:-2.21957pt;width:54.525002px;" version="1.1" viewbox="0 0 54.525002 13.45" width="54.525002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.5390692" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="10.702568" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="17.579218" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="25.218552" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="37.258942" y="0"> 0</tspan> </text> </g> </g> </svg>否则)。假设L [C]发布概要文件和脂质体膜的纳米细胞相似,我们可以设置<svg height="17.575001" id="M99" style="vertical-align:-4.02643pt;width:51.537498px;" version="1.1" viewbox="0 0 51.537498 17.575001" width="51.537498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,17.575)"> <g transform="translate(72,-57.94)"> <text transform="matrix(1,0,0,-1,-71.95,62)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.84,58.88)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-55.67,62)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-37.52,67.01)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="0" y="9.0200005"> </tspan> </text> </g> </g> </svg>和<svg height="17.575001" id="M100" style="vertical-align:-4.02643pt;width:52.25px;" version="1.1" viewbox="0 0 52.25 17.575001" width="52.25" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,17.575)"> <g transform="translate(72,-57.94)"> <text transform="matrix(1,0,0,-1,-71.95,62)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.55,58.88)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-55.38,62)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-36.94,67.01)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="0" y="9.0200005"> </tspan> </text> </g> </g> </svg>,在这种情况下(<一个href="#EEq2">7</一个>)意味着<svg height="14.2375" id="M101" style="vertical-align:-3.13504pt;width:58.299999px;" version="1.1" viewbox="0 0 58.299999 14.2375" width="58.299999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.2375)"> <g transform="translate(72,-60.61)"> <text transform="matrix(1,0,0,-1,-71.95,63.79)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.31,60.66)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</tspan> </text> <text transform="matrix(1,0,0,-1,-52.96,63.79)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-30.28,60.66)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</tspan> </text> </g> </g> </svg>。基于森古普塔et al。<一个href="#B19">19</一个>我们把<svg height="14.75" id="M102" style="vertical-align:-3.25792pt;width:62.400002px;" version="1.1" viewbox="0 0 62.400002 14.75" width="62.400002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.75)"> <g transform="translate(72,-60.2)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.84,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> N</tspan> <tspan style="font-size: 8.75px; " x="6.2401762" y="0"> C</tspan> </text> <text transform="matrix(1,0,0,-1,-49.8,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.040389" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="18.291889" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.417639" y="0"> 3</tspan> </text> </g> </g> </svg>和<svg height="14.9375" id="M103" style="vertical-align:-3.25792pt;width:58.849998px;" version="1.1" viewbox="0 0 58.849998 14.9375" width="58.849998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.9375)"> <g transform="translate(72,-60.05)"> <text transform="matrix(1,0,0,-1,-71.95,63.35)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.55,60.22)"> <tspan style="font-size: 8.75px; " x="0" y="0"> N</tspan> <tspan style="font-size: 8.75px; " x="6.2401762" y="0"> C</tspan> </text> <text transform="matrix(1,0,0,-1,-49.51,63.35)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 5</tspan> </text> </g> </g> </svg>天,<svg height="14.6" id="M104" style="vertical-align:-3.13504pt;width:55.0625px;" version="1.1" viewbox="0 0 55.0625 14.6" width="55.0625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.84,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-55.67,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.405136" y="0"> 1</tspan> </text> </g> </g> </svg>和<svg height="14.6" id="M105" style="vertical-align:-3.13504pt;width:43.700001px;" version="1.1" viewbox="0 0 43.700001 14.6" width="43.700001" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.55,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-55.38,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 2</tspan> </text> </g> </g> </svg>天。为我们修改后的纳米细胞疗法(见部分<一个href="#sec3">3</一个>),我们使用相同的治疗安排数控(CD),但需要<svg height="14.75" id="M106" style="vertical-align:-3.25792pt;width:62.400002px;" version="1.1" viewbox="0 0 62.400002 14.75" width="62.400002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.75)"> <g transform="translate(72,-60.2)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.84,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> N</tspan> <tspan style="font-size: 8.75px; " x="6.2401762" y="0"> C</tspan> </text> <text transform="matrix(1,0,0,-1,-49.8,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.040389" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="18.291889" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.417639" y="0"> 8</tspan> </text> </g> </g> </svg>在(<一个href="#EEq4">10</一个>)与确定一个适当的归一化因素(<一个href="#EEq2">7</一个>)。这将确保所有联合治疗的纳米细胞和脂质体释放相同的combretastatin总量和阿霉素。</p><p>这个函数<svg height="14.7125" id="M107" style="vertical-align:-3.2316pt;width:28.625px;" version="1.1" viewbox="0 0 28.625 14.7125" width="28.625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> Γ</tspan> </text> <text transform="matrix(1,0,0,-1,-64.61,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.39,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> </text> </g> </g> </svg>在(<一个href="#EEq1.3">4</一个>)描述了(平均)浓度的脂质体和纳米细胞的血管。在使用相同的函数<svg height="14.7125" id="M108" style="vertical-align:-3.2316pt;width:28.625px;" version="1.1" viewbox="0 0 28.625 14.7125" width="28.625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> Γ</tspan> </text> <text transform="matrix(1,0,0,-1,-64.61,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.39,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> </text> </g> </g> </svg>脂质体和纳米细胞我们假设,一旦治疗后,血管的药物浓度变化只是由于一些自然衰变(如吸附)独立于粒子的化学成分。因此,我们组<span class="equation" id="EEq5"> <svg height="48.1875" id="M109" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 48.1875" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,48.1875)"> <g transform="translate(72,-33.45)"> <text transform="matrix(1,0,0,-1,116.65,49.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> Γ</tspan> </text> <text transform="matrix(1,0,0,-1,123.99,46.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,129.29,49.61)"> <tspan style="font-size: 12.50px; " x="36.389999" y="2.52"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> <tspan style="font-size: 12.50px; " x="15.716271" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="27.744158" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="42.240002" y="0.0099999998"> </tspan> <tspan style="font-size: 12.50px; " x="48.929104" y="0.0099999998"> −</tspan> <tspan style="font-size: 12.50px; " x="60.269325" y="0.0099999998"> </tspan> </text> <text transform="matrix(1,0,0,-1,193.48,46.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,196.7,47.09)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="30.16" y="7.2199998"> </tspan> <tspan style="font-size: 12.50px; " x="40.259998" y="-2.51"> −</tspan> <tspan style="font-size: 12.50px; " x="50.02" y="-10.58"> </tspan> <tspan style="font-size: 12.50px; " x="7.9400001" y="-2.51"> e</tspan> <tspan style="font-size: 12.50px; " x="13.491332" y="-2.51"> x</tspan> <tspan style="font-size: 12.50px; " x="19.742832" y="-2.51"> p</tspan> <tspan style="font-size: 12.50px; " x="55.869999" y="-13.09"> </tspan> <tspan style="font-size: 12.50px; " x="62.559105" y="-13.09"> −</tspan> <tspan style="font-size: 12.50px; " x="73.899323" y="-13.09"> </tspan> </text> <text transform="matrix(1,0,0,-1,274.52,57.05)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,277.74,57.67)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <g> <path d="m 246.72,52.73 36.87,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,258.18,40.85)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,264.59,37.72)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,284.79,39.87)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="12.18" y="-9.7299995"> ,</tspan> <tspan style="font-size: 12.50px; " x="183.08" y="-9.7299995"> (</tspan> <tspan style="font-size: 12.50px; " x="187.2435" y="-9.7299995"> 1</tspan> <tspan style="font-size: 12.50px; " x="193.495" y="-9.7299995"> 1</tspan> <tspan style="font-size: 12.50px; " x="199.74651" y="-9.7299995"> )</tspan> </text> </g> </g> </svg></span>如上所述,<svg height="13.0125" id="M110" style="vertical-align:-3.2316pt;width:9.0375004px;" version="1.1" viewbox="0 0 9.0375004 13.0125" width="9.0375004" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.0125)"> <g transform="translate(72,-61.59)"> <text transform="matrix(1,0,0,-1,-71.95,64.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-68.04,61.74)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>再一次政府时期。有一些迹象(森古普塔et al。<一个href="#B19">19</一个>),参见图<一个href="//www.newsama.com/journals/cmmm/2011/790721/fig1/" target="_blank">1</一个>),<svg height="14.7125" id="M111" style="vertical-align:-3.2316pt;width:28.625px;" version="1.1" viewbox="0 0 28.625 14.7125" width="28.625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> Γ</tspan> </text> <text transform="matrix(1,0,0,-1,-64.61,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.39,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> </text> </g> </g> </svg>脂质体和纳米细胞不同,增加周围组织交付的纳米细胞肿瘤血管正常化以外的一种机制。这将进一步提高数控(CD)的影响相对于L (CD)通过增加药物的数量交付给肿瘤。然而,为了允许直接调查的时间瞄准机制提出的森古普塔et al。<一个href="#B19">19</一个>),我们把<svg height="14.7125" id="M112" style="vertical-align:-3.2316pt;width:28.625px;" version="1.1" viewbox="0 0 28.625 14.7125" width="28.625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> Γ</tspan> </text> <text transform="matrix(1,0,0,-1,-64.61,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.39,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</tspan> </text> </g> </g> </svg>传统疗法一样的纳米细胞治疗和设置<svg height="10.875" id="M113" style="vertical-align:-3.25792pt;width:60.650002px;" version="1.1" viewbox="0 0 60.650002 10.875" width="60.650002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.875)"> <g transform="translate(72,-63.3)"> <text transform="matrix(1,0,0,-1,-71.95,66.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.55,63.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-54.53,66.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-36.09,63.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> N</tspan> <tspan style="font-size: 8.75px; " x="6.2314239" y="0"> C</tspan> </text> </g> </g> </svg>。</p><h5我d="sec2.5">2.5。参数化</h5><p>免费的抗血管和化疗药物小颗粒可以被认为具有扩散特征类似于营养如氧气,实验数据是现成的。因此,我们组<svg height="19.075001" id="M114" style="vertical-align:-3.25793pt;width:56.862499px;" version="1.1" viewbox="0 0 56.862499 19.075001" width="56.862499" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,19.075)"> <g transform="translate(72,-56.74)"> <text transform="matrix(1,0,0,-1,-70.42,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-1.53" y="2.54"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.89,56.91)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 3</tspan> </text> <text transform="matrix(1,0,0,-1,-53.54,60.03)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="13.57" y="-2.54"> </tspan> <tspan style="font-size: 12.50px; " x="12.04" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-31.44,56.91)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</tspan> </text> </g> </g> </svg>在(<一个href="#EEq1.4">5</一个>)和(<一个href="#EEq1.4">6</一个>)和使用的价值<svg height="19.075001" id="M115" style="vertical-align:-3.25793pt;width:18.799999px;" version="1.1" viewbox="0 0 18.799999 19.075001" width="18.799999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,19.075)"> <g transform="translate(72,-56.74)"> <text transform="matrix(1,0,0,-1,-70.42,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-1.53" y="2.54"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.89,56.91)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 3</tspan> </text> </g> </g> </svg>类似于自由氧的扩散常数Kohandel et al。<一个href="#B12">22</一个>]。正如前面提到的,<svg height="13.45" id="M116" style="vertical-align:-2.21957pt;width:41.625px;" version="1.1" viewbox="0 0 41.625 13.45" width="41.625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.8771296" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="13.040629" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="19.917278" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="25.118526" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="29.031965" y="0"> )</tspan> </text> </g> </g> </svg>代表平均分布的血管(而不是脉管系统的具体模式);因此,药物的扩散系数(或营养)不是相同的顺序从单个血管扩散。此外,由于化疗药物释放的纳米细胞通过血管运输走相同的方式为数控[D]和数控(CD)<svg height="19.075001" id="M117" style="vertical-align:-3.25793pt;width:56.862499px;" version="1.1" viewbox="0 0 56.862499 19.075001" width="56.862499" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,19.075)"> <g transform="translate(72,-56.74)"> <text transform="matrix(1,0,0,-1,-70.42,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-1.53" y="2.54"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.89,56.91)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 3</tspan> </text> <text transform="matrix(1,0,0,-1,-53.54,60.03)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="13.57" y="-2.54"> </tspan> <tspan style="font-size: 12.50px; " x="12.04" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-31.44,56.91)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</tspan> </text> </g> </g> </svg>,我们使用相同的再吸收速率<svg height="14.7125" id="M118" style="vertical-align:-2.29482pt;width:9.6374998px;" version="1.1" viewbox="0 0 9.6374998 14.7125" width="9.6374998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.64,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.30007201" y="0"> </tspan> </text> </g> </g> </svg>所有的治疗方法。同样在Kohandel et al。<一个href="#B12">22</一个>免费的氧气,我们假定的自然衰变<svg height="7.1875" id="M119" style="vertical-align:-0.13794pt;width:7.3874998px;" version="1.1" viewbox="0 0 7.3874998 7.1875" width="7.3874998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.1875)"> <g transform="translate(72,-66.25)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>和<svg height="10.75" id="M120" style="vertical-align:-0.15048pt;width:9.375px;" version="1.1" viewbox="0 0 9.375 10.75" width="9.375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.75)"> <g transform="translate(72,-63.4)"> <text transform="matrix(1,0,0,-1,-71.95,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>不是太大,因此,衰变常数吗<svg height="13.9125" id="M121" style="vertical-align:-0.17555pt;width:23.225px;" version="1.1" viewbox="0 0 23.225 13.9125" width="23.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.9125)"> <g transform="translate(72,-60.87)"> <text transform="matrix(1,0,0,-1,-65.94,61.03)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.00144" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.67,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> </g> </g> </svg>和<svg height="13.9125" id="M122" style="vertical-align:-0.17555pt;width:24.525px;" version="1.1" viewbox="0 0 24.525 13.9125" width="24.525" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.9125)"> <g transform="translate(72,-60.87)"> <text transform="matrix(1,0,0,-1,-65.94,61.03)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.00144" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.67,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> </g> </g> </svg>数值小于<svg height="14.7125" id="M123" style="vertical-align:-2.29482pt;width:9.6374998px;" version="1.1" viewbox="0 0 9.6374998 14.7125" width="9.6374998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.64,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.30007201" y="0"> </tspan> </text> </g> </g> </svg>。此外,combretastatin释放脂质体衰变的速度比释放阿霉素纳米细胞(<一个href="#B19">19</一个>),因此,我们把<svg height="14.15" id="M124" style="vertical-align:-0.30096pt;width:67px;" version="1.1" viewbox="0 0 67 14.15" width="67" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.15)"> <g transform="translate(72,-60.68)"> <text transform="matrix(1,0,0,-1,-65.94,61.03)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.00144" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.67,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,-50,61.03)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ></tspan> <tspan style="font-size: 12.50px; " x="18.041828" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="12.040389" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-31.69,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> </g> </g> </svg>。另一方面,你可能希望释放阿霉素脂质体在治疗L (CD)衰变速度比阿霉素纳米细胞的释放。这将进一步降低L (CD)的效率相对于数控(CD),但是为了避免扩散参数我们使用相同的值<svg height="13.9125" id="M125" style="vertical-align:-0.17555pt;width:24.525px;" version="1.1" viewbox="0 0 24.525 13.9125" width="24.525" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.9125)"> <g transform="translate(72,-60.87)"> <text transform="matrix(1,0,0,-1,-65.94,61.03)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.00144" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.67,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> </g> </g> </svg>所有的治疗方法。</p><p>药物管理的数量可以包含在我们的模型系数的值<svg height="17.049999" id="M126" style="vertical-align:-0.20064pt;width:23.825001px;" version="1.1" viewbox="0 0 23.825001 17.049999" width="23.825001" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,17.05)"> <g transform="translate(72,-58.36)"> <text transform="matrix(1,0,0,-1,-65.69,61.34)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.2600002" y="2.73"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.19,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> </g> </g> </svg>和<svg height="17.049999" id="M127" style="vertical-align:-0.20064pt;width:25.137501px;" version="1.1" viewbox="0 0 25.137501 17.049999" width="25.137501" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,17.05)"> <g transform="translate(72,-58.36)"> <text transform="matrix(1,0,0,-1,-65.69,61.34)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.2600002" y="2.73"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.19,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> </g> </g> </svg>。在实验中所描述的森古普塔et al。<一个href="#B19">19</一个>co米bretastatin]约一百倍阿霉素注射,因此,我们<svg height="17.049999" id="M128" style="vertical-align:-0.20064pt;width:94.275002px;" version="1.1" viewbox="0 0 94.275002 17.049999" width="94.275002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,17.05)"> <g transform="translate(72,-58.36)"> <text transform="matrix(1,0,0,-1,-65.69,61.34)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.2600002" y="2.73"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.19,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,-49.51,58.61)"> <tspan style="font-size: 12.50px; " x="39.130001" y="-2.73"> ̃</tspan> <tspan style="font-size: 12.50px; " x="32.869999" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="24.530886" y="0"> 0</tspan> </text> <text transform="matrix(1,0,0,-1,-9.87,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> </g> </g> </svg>。此外,常量<svg height="18.525" id="M129" style="vertical-align:-0.17555pt;width:26.575001px;" version="1.1" viewbox="0 0 26.575001 18.525" width="26.575001" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,18.525)"> <g transform="translate(72,-57.18)"> <text transform="matrix(1,0,0,-1,-69.07,59.94)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-2.8800001" y="2.71"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.99,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> </g> </g> </svg>和<svg height="18.525" id="M130" style="vertical-align:-0.17555pt;width:27.887501px;" version="1.1" viewbox="0 0 27.887501 18.525" width="27.887501" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,18.525)"> <g transform="translate(72,-57.18)"> <text transform="matrix(1,0,0,-1,-69.07,59.94)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-2.8800001" y="2.71"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.99,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> </g> </g> </svg>确定给定的疗法的有效性,因此我们的模型的关键参数。允许定量比较不同组合疗法的效果,我们使用相同的值<svg height="18.525" id="M131" style="vertical-align:-0.17555pt;width:26.575001px;" version="1.1" viewbox="0 0 26.575001 18.525" width="26.575001" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,18.525)"> <g transform="translate(72,-57.18)"> <text transform="matrix(1,0,0,-1,-69.07,59.94)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-2.8800001" y="2.71"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.99,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> </g> </g> </svg>和<svg height="18.525" id="M132" style="vertical-align:-0.17555pt;width:27.887501px;" version="1.1" viewbox="0 0 27.887501 18.525" width="27.887501" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,18.525)"> <g transform="translate(72,-57.18)"> <text transform="matrix(1,0,0,-1,-69.07,59.94)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-2.8800001" y="2.71"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.99,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> </g> </g> </svg>单独和联合疗法。从而是假设一个给定的影响治疗代理不会受到另一个治疗代理的存在与否。所有参数的值出现在我们的模型是固定的配件体积V曲线,L [C],数控[D]对应的实验结果(<一个href="#B19">19</一个>]。表<一个href="//www.newsama.com/journals/cmmm/2011/790721/tab1/" target="_blank">1</一个>总结了参数值用于我们的模拟参数的敏感性分析(见附录)。联合治疗的结果然后预测模型没有任何进一步的假设。</p><div class="floats-partial-section partial-other-wrapper" data-section="tab1"> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">表1</span> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/cmmm/2011/790721/tab1/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> 参数的数值(1)和(<一个href="#EEq3">9</一个>)用于我们的模拟。除了显示的值,我们使用dimensionful方程<svg height="14.6" id="M133" style="vertical-align:-3.13504pt;width:65.300003px;" version="1.1" viewbox="0 0 65.300003 14.6" width="65.300003" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.07,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-53.73,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.040389" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="18.291889" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.417639" y="0"> 3</tspan> <tspan style="font-size: 12.50px; " x="27.66914" y="0"> 2</tspan> </text> </g> </g> </svg>毫米<sup>2</sup>肺癌和/天<svg height="14.725" id="M134" style="vertical-align:-3.13504pt;width:65.300003px;" version="1.1" viewbox="0 0 65.300003 14.725" width="65.300003" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.725)"> <g transform="translate(72,-60.22)"> <text transform="matrix(1,0,0,-1,-71.95,63.4)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.07,60.27)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> <text transform="matrix(1,0,0,-1,-53.73,63.4)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.040389" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="18.291889" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.417639" y="0"> 4</tspan> <tspan style="font-size: 12.50px; " x="27.66914" y="0"> 6</tspan> </text> </g> </g> </svg>毫米<sup>2</sup>黑色素瘤/天,<svg height="13.7375" id="M135" style="vertical-align:-2.29482pt;width:54.712502px;" version="1.1" viewbox="0 0 54.712502 13.7375" width="54.712502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.7375)"> <g transform="translate(72,-61.01)"> <text transform="matrix(1,0,0,-1,-71.95,63.35)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="9.7398367" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="21.780226" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="28.031727" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="31.157476" y="0"> 3</tspan> <tspan style="font-size: 12.50px; " x="37.408978" y="0"> 5</tspan> </text> </g> </g> </svg>一天<sup>1</sup>黑色素瘤和肺癌(见部分<一个href="#sec3.1">3.1</一个>),以及一个阈值检测能力的肿瘤细胞<svg height="14.7125" id="M136" style="vertical-align:-3.22282pt;width:63.712502px;" version="1.1" viewbox="0 0 63.712502 14.7125" width="63.712502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-66.76,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="2.7393761" y="0"> ℎ</tspan> </text> <text transform="matrix(1,0,0,-1,-55,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.405136" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="27.656635" y="0"> 9</tspan> </text> </g> </g> </svg>(<一个href="#B12">22</一个>]。作为主要解释文本<svg height="19.075001" id="M137" style="vertical-align:-3.25793pt;width:56.862499px;" version="1.1" viewbox="0 0 56.862499 19.075001" width="56.862499" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,19.075)"> <g transform="translate(72,-56.74)"> <text transform="matrix(1,0,0,-1,-70.42,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-1.53" y="2.54"> </tspan> </text> <text transform="matrix(1,0,0,-1,-61.89,56.91)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 3</tspan> </text> <text transform="matrix(1,0,0,-1,-53.54,60.03)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="13.57" y="-2.54"> </tspan> <tspan style="font-size: 12.50px; " x="12.04" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-31.44,56.91)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</tspan> </text> </g> </g> </svg>和<svg height="17.049999" id="M138" style="vertical-align:-0.20064pt;width:91.662498px;" version="1.1" viewbox="0 0 91.662498 17.049999" width="91.662498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,17.05)"> <g transform="translate(72,-58.36)"> <text transform="matrix(1,0,0,-1,-65.69,61.34)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.2600002" y="2.73"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.19,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,-49.51,58.61)"> <tspan style="font-size: 12.50px; " x="37.049999" y="-2.73"> ̃</tspan> <tspan style="font-size: 12.50px; " x="30.790001" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="24.530886" y="0"> 0</tspan> </text> <text transform="matrix(1,0,0,-1,-11.96,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> </g> </g> </svg>。化疗和抗血管新生疗法的有效性是参数化的<svg height="18.75" id="M139" style="vertical-align:-0.17555pt;width:74.625px;" version="1.1" viewbox="0 0 74.625 18.75" width="74.625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,18.75)"> <g transform="translate(72,-57)"> <text transform="matrix(1,0,0,-1,-69.07,59.94)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-2.8800001" y="2.71"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.99,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,-46.27,57.23)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.405136" y="0"> 6</tspan> <tspan style="font-size: 12.50px; " x="27.656635" y="0"> 5</tspan> </text> </g> </g> </svg>和<svg height="18.75" id="M140" style="vertical-align:-0.17555pt;width:65.5px;" version="1.1" viewbox="0 0 65.5 18.75" width="65.5" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,18.75)"> <g transform="translate(72,-57)"> <text transform="matrix(1,0,0,-1,-69.07,59.94)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-2.8800001" y="2.71"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.99,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,-47.31,57.23)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.405136" y="0"> 1</tspan> </text> </g> </g> </svg>肺癌,<svg height="18.75" id="M141" style="vertical-align:-0.17555pt;width:55.087502px;" version="1.1" viewbox="0 0 55.087502 18.75" width="55.087502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,18.75)"> <g transform="translate(72,-57)"> <text transform="matrix(1,0,0,-1,-69.07,59.94)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-2.8800001" y="2.71"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.99,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,-46.27,57.23)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 3</tspan> </text> </g> </g> </svg>和<svg height="18.75" id="M142" style="vertical-align:-0.17555pt;width:65.5px;" version="1.1" viewbox="0 0 65.5 18.75" width="65.5" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,18.75)"> <g transform="translate(72,-57)"> <text transform="matrix(1,0,0,-1,-69.07,59.94)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-2.8800001" y="2.71"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.99,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,-47.31,57.23)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.405136" y="0"> 3</tspan> </text> </g> </g> </svg>黑色素瘤(见部分<一个href="#sec3.1">3.1</一个>)。</div> <a class="table-thumb-overlay" href="//www.newsama.com/journals/cmmm/2011/790721/tab1" target="_blank" aria-label="View full page"></a> </div> </div> <p>当我们在我们的模型中,考虑各种不同的交互,目的是不排除任何可能成功的纳米细胞治疗的机制<我>先天的</我>,我们发现只有三个参数<svg height="14.2375" id="M157" style="vertical-align:-3.13504pt;width:18.5625px;" version="1.1" viewbox="0 0 18.5625 14.2375" width="18.5625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.2375)"> <g transform="translate(72,-60.61)"> <text transform="matrix(1,0,0,-1,-71.95,63.79)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.07,60.66)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> </g> </g> </svg>,<svg height="18.525" id="M158" style="vertical-align:-0.17555pt;width:26.575001px;" version="1.1" viewbox="0 0 26.575001 18.525" width="26.575001" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,18.525)"> <g transform="translate(72,-57.18)"> <text transform="matrix(1,0,0,-1,-69.07,59.94)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-2.8800001" y="2.71"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.99,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> </g> </g> </svg>,<svg height="18.525" id="M159" style="vertical-align:-0.17555pt;width:27.887501px;" version="1.1" viewbox="0 0 27.887501 18.525" width="27.887501" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,18.525)"> <g transform="translate(72,-57.18)"> <text transform="matrix(1,0,0,-1,-69.07,59.94)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-2.8800001" y="2.71"> </tspan> </text> <text transform="matrix(1,0,0,-1,-62.99,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> </g> </g> </svg>需要调整区分肺癌和黑素瘤。此外,我们还发现,肺癌和黑色素瘤的成功纳米细胞治疗严重依赖于所使用的时间发布概要文件森古普塔et al。<一个href="#B19">19</一个>)和重吸收的可能性的化疗药物在血液中(见部分<一个href="#sec3">3</一个>),这是参数化的<svg height="14.7125" id="M160" style="vertical-align:-2.29482pt;width:9.6374998px;" version="1.1" viewbox="0 0 9.6374998 14.7125" width="9.6374998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.64,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.30007201" y="0"> </tspan> </text> </g> </g> </svg>。如Kohandel et al。<一个href="#B12">22</一个>),我们使用规范化的高斯初始条件<svg height="13.45" id="M161" style="vertical-align:-2.21957pt;width:38.299999px;" version="1.1" viewbox="0 0 38.299999 13.45" width="38.299999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="6.2139912" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="10.37749" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="17.254141" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="22.455387" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="26.368828" y="0"> )</tspan> </text> </g> </g> </svg>与方差<svg height="11.1" id="M162" style="vertical-align:-0.17555pt;width:56.037498px;" version="1.1" viewbox="0 0 56.037498 11.1" width="56.037498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.1)"> <g transform="translate(72,-63.12)"> <text transform="matrix(1,0,0,-1,-71.95,63.35)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="10.802592" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="22.842981" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="29.094481" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="32.22023" y="0"> 3</tspan> <tspan style="font-size: 12.50px; " x="38.471729" y="0"> 5</tspan> </text> </g> </g> </svg>和一个随机的初始条件<svg height="13.45" id="M163" style="vertical-align:-2.21957pt;width:41.625px;" version="1.1" viewbox="0 0 41.625 13.45" width="41.625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="8.8771296" y="0"> (</tspan> <tspan style="font-size: 12.50px; " x="13.040629" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="19.917278" y="0"> ,</tspan> <tspan style="font-size: 12.50px; " x="25.118526" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="29.031965" y="0"> )</tspan> </text> </g> </g> </svg>均匀分布在0和1之间。零初始条件被认为是药物的浓度。所有模拟上执行一个立方网格<svg height="11.2625" id="M164" style="vertical-align:-0.3135pt;width:91.324997px;" version="1.1" viewbox="0 0 91.324997 11.2625" width="91.324997" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.2625)"> <g transform="translate(72,-62.99)"> <text transform="matrix(1,0,0,-1,-71.95,63.35)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 5</tspan> <tspan style="font-size: 12.50px; " x="6.2515001" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="17.354164" y="0"> ×</tspan> <tspan style="font-size: 12.50px; " x="30.219751" y="0"> 5</tspan> <tspan style="font-size: 12.50px; " x="36.471252" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="47.586418" y="0"> ×</tspan> <tspan style="font-size: 12.50px; " x="60.452003" y="0"> 5</tspan> <tspan style="font-size: 12.50px; " x="66.703506" y="0"> 0</tspan> </text> </g> </g> </svg>分,无需通量边界条件。</p><h4我d="results-and-discussion">3所示。结果与讨论</h4><h5我d="sec3.1">3.1。模型结果的一致性</h5><p>确认我们的模型,数值模拟的实验协议执行森古普塔et al。<一个href="#B19">19</一个>在肺癌和黑色素瘤(见图<一个href="//www.newsama.com/journals/cmmm/2011/790721/fig2/" target="_blank">2</一个>)。在这些实验中,<svg height="14.5" id="M165" style="vertical-align:-0.3135pt;width:58.325001px;" version="1.1" viewbox="0 0 58.325001 14.5" width="58.325001" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.5)"> <g transform="translate(72,-60.4)"> <text transform="matrix(1,0,0,-1,-71.95,60.76)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 2</tspan> <tspan style="font-size: 12.50px; " x="6.2515001" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="9.3772497" y="0"> 5</tspan> <tspan style="font-size: 12.50px; " x="18.404415" y="0"> ×</tspan> <tspan style="font-size: 12.50px; " x="29.182001" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="35.433502" y="0"> 0</tspan> </text> <text transform="matrix(1,0,0,-1,-30.26,65.93)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 5</tspan> </text> </g> </g> </svg>路易斯肺癌细胞或<svg height="14.5" id="M166" style="vertical-align:-0.3135pt;width:46.612499px;" version="1.1" viewbox="0 0 46.612499 14.5" width="46.612499" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.5)"> <g transform="translate(72,-60.4)"> <text transform="matrix(1,0,0,-1,-71.95,60.76)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 3</tspan> <tspan style="font-size: 12.50px; " x="9.0271664" y="0"> ×</tspan> <tspan style="font-size: 12.50px; " x="19.804752" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="26.056252" y="0"> 0</tspan> </text> <text transform="matrix(1,0,0,-1,-39.64,65.93)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 5</tspan> </text> </g> </g> </svg>GFP-positive BL6 / F10黑色素瘤细胞植入男性C57 / BL6老鼠,和治疗开始时肿瘤达到50 mm<sup>3</sup>体积(大约8天)。肿瘤生长和血管形成的动力学,以及对照组的数据点(V,红色),用于估计相关的模型参数为肺癌(见表<一个href="//www.newsama.com/journals/cmmm/2011/790721/tab1/" target="_blank">1</一个>)。实验治疗时间表,以及药物的药代学和药效学,用于模拟以适应单一的数据管理抗血管新生疗法(combretastatin-encapsulated脂质体,L [C],棕色)和化疗(含阿霉素纳米细胞,但缺乏combretastatin数控[D],蓝色)。黑色素瘤的相应曲线是通过修改三个模型参数描述癌细胞的扩散和治疗药物的作用在血管网络和癌细胞(见部分<一个href="#sec2">2</一个>)。然后我们进行数值模拟与传统的估计参数预测结果(脂质体阿霉素和combretastatin封装,L (CD),绿色)和纳米细胞(数控(CD)、紫色)方法的结合反血管增生和细胞毒性治疗。</p><div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-bfabfad90fe2995fa64f57310ac34d16"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(一)路易斯肺癌" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/figures/790721.fig.002a.jpg"> <br> <strong>(一)路易斯肺癌</strong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(b) B16转椅/ F10黑色素瘤" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/figures/790721.fig.002b.jpg"> <br> <strong>(b) B16转椅/ F10黑色素瘤</strong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-bfabfad90fe2995fa64f57310ac34d16 partial-carousel-thumbnail"> <button aria-label="Slide to (a) Lewis lung carcinoma" class="partial-carousel-dot"><img loading="lazy" alt="(一)路易斯肺癌" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/thumbnails/790721.fig.002a_th.jpg"><br><strong>(一)路易斯肺癌</strong></button> <button aria-label="Slide to (b) B16/F10 melanoma" class="partial-carousel-dot"><img loading="lazy" alt="(b) B16转椅/ F10黑色素瘤" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/thumbnails/790721.fig.002b_th.jpg"><br><strong>(b) B16转椅/ F10黑色素瘤</strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-bfabfad90fe2995fa64f57310ac34d16 partial-carousel-next-prev"> <button aria-label="Previous" class="carousel-prev"></button> <button aria-label="Next" class="carousel-next"></button> </div> </div> </div> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">图2</span> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/cmmm/2011/790721/fig2/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>肿瘤体积曲线的肺癌(a)和(b)黑色素瘤没有治疗(V),获得纳米细胞只包含阿霉素(数控[D]),脂质体仅包含combretastatin (L [C]),与combretastatin和阿霉素脂质体(L (CD)),纳米细胞combretastatin和阿霉素(数控(CD))和纳米细胞combretastatin和阿霉素但延迟释放阿霉素(NC (CD)和<svg height="14.75" id="M167" style="vertical-align:-3.25792pt" version="1.1" viewbox="0 0 62.400002 14.75" width="62.400002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.75)"> <g transform="translate(72,-60.2)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.84,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> N</tspan> <tspan style="font-size: 8.75px; " x="6.2401762" y="0"> C</tspan> </text> <text transform="matrix(1,0,0,-1,-49.8,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.040389" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="18.291889" y="0"> 。</tspan> <tspan style="font-size: 12.50px; " x="21.417639" y="0"> 8</tspan> </text> </g> </g> </svg>)。坚实的曲线获得的积分(<一个href="https://static.hindawi.com/articles/cmmm/volume-2011/790721/figures/790721/">1</一个>)- - - - - -(<一个href="https://static.hindawi.com/articles/cmmm/volume-2011/790721/figures/790721/">6</一个>节)<一个href="https://static.hindawi.com/articles/cmmm/volume-2011/790721/figures/790721/">2</一个>,从实验数据点被森古普塔et al。<一个href="https://static.hindawi.com/articles/cmmm/volume-2011/790721/figures/790721/">19</一个>]。相同的药物释放总量由脂质体和纳米细胞的治疗策略相结合,这对数控对应发布的两倍[D]和L [C]。</td> </tr> </tbody> </table> </div> </div> </div> </div> <p>如图<一个href="//www.newsama.com/journals/cmmm/2011/790721/fig2/" target="_blank">2</一个>数值结果(实线)从我们的现象学模型获得繁殖实验中观察到的主要趋势,森古普塔et al。<一个href="#B19">19</一个>)(点)肺癌和黑色素瘤。虽然combretastatin和阿霉素的传统组合产生倍增效应相比,单一管理combretastatin或阿霉素纳米细胞明显表现出更明显的效果与相同数量的药物管理。我们模拟强烈支持的假设的增加影响纳米细胞治疗主要是由于时间释放通过纳米细胞(<一个href="#B19">19</一个>),从数学的角度来看是唯一特性区分L (CD)和数控(CD)在我们的模型中(见部分<一个href="#sec2">2</一个>)。这是在下面进一步讨论。</p><p>在这项研究中,森古普塔et al。<一个href="#B19">19</一个>),结果单一疗法数控[D]和L [C]相比也共同服用数控的[D]和L [C](数控[D] + L [C])。然而,数控[D] + L [C]只显示效果相比可以忽略不计的单独治疗。这可能是由于限制纳米细胞的总数或脂质体可被肿瘤组织在任何给定的时间。这种限制并不影响任何其他更有效的组合策略考虑森古普塔et al。<一个href="#B19">19</一个>),因此,我们不讨论这种情况下在我们的建模方法。</p><h5我d="sec3.2">3.2。协同效应的纳米细胞治疗</h5><p>我们的模型预测纳米细胞治疗可以产生的综合效应<我>大于各部分的总和</我>通过两种不同的机制见图<一个href="//www.newsama.com/journals/cmmm/2011/790721/fig3/" target="_blank">3</一个>。首先,瞬态正常化造成抗血管新生疗法提高交付额外的纳米细胞的肿瘤组织。这反过来增加后续释放化疗的效果。其次,抗血管新生疗法还可以切断肿瘤的血液供应,有效陷阱细胞毒性药物在肿瘤组织内。因此,少量的免费化疗药物运输远离肿瘤组织。根据我们的模拟,后者机制是至关重要的获取上级报告的数控(CD)结果由森古普塔et al。<一个href="#B19">19</一个>],而规范化只带来很小的有效性增加数控(CD)相对于L (CD)。然而,正如稍后讨论,标准化仍然可以用来进一步提高纳米细胞治疗的疗效。</p><div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-a478694a2be4571412abd066fabf9726"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/figures/790721.fig.003.jpg"> <br> <strong></strong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-a478694a2be4571412abd066fabf9726 partial-carousel-thumbnail"> <button aria-label="Slide to " class="partial-carousel-dot"><img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/thumbnails/790721.fig.003_th.jpg"><br><strong></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-a478694a2be4571412abd066fabf9726 partial-carousel-next-prev"> <button aria-label="Previous" class="carousel-prev"></button> <button aria-label="Next" class="carousel-next"></button> </div> </div> </div> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">图3</span> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/cmmm/2011/790721/fig3/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>机制的时间针对肿瘤细胞和neovasculature。(一)纳米细胞通过neovasculature传递到肿瘤组织和快速释放抗血管新生药物。(b)血管崩溃导致化疗药物在肿瘤组织的捕获,从而防止再吸收到血液中。这是根据我们的数学模型的主要机制负责上级纳米细胞治疗的结果发现森古普塔et al。<一个href="https://static.hindawi.com/articles/cmmm/volume-2011/790721/figures/790721/">19</一个>]。(c)产生的肿瘤血管正常化抗血管新生疗法导致短暂的“机会之窗”<一个href="https://static.hindawi.com/articles/cmmm/volume-2011/790721/figures/790721/">2</一个>)在此期间的纳米细胞进入肿瘤组织是提高。(d)我们的模型表明,通过明智的时机发布概要文件规范化和血管崩溃之间的相互作用可以用来改善纳米细胞治疗的疗效。</td> </tr> </tbody> </table> </div> </div> </div> </div> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-752066567d60e5c34da6b5df80acb32a"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/figures/790721.fig.004.jpg"> <br> <strong></strong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-752066567d60e5c34da6b5df80acb32a partial-carousel-thumbnail"> <button aria-label="Slide to " class="partial-carousel-dot"><img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/thumbnails/790721.fig.004_th.jpg"><br><strong></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-752066567d60e5c34da6b5df80acb32a partial-carousel-next-prev"> <button aria-label="Previous" class="carousel-prev"></button> <button aria-label="Next" class="carousel-next"></button> </div> </div> </div> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">图4</span> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/cmmm/2011/790721/fig4/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>灵敏度分析对L (CD)和数控(CD)路易斯肺癌。每组由四个颜色列对应下面的参数直接表示<svg height="7.1624999" id="M168" style="vertical-align:-0.11285pt" version="1.1" viewbox="0 0 8.7250004 7.1624999" width="8.7250004" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.1625)"> <g transform="translate(72,-66.27)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>设在。</td> </tr> </tbody> </table> </div> </div> </div> </div> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-d7a0a0bb065f381ae246c4a152ac8b60"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(1)增加了5% (Lewis肺癌carinoma)" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/figures/790721.fig.005a.jpg"> <br> <strong> <table> <tbody> <tr> <td><b>(一)</b> <svg height="10.925" id="M171" style="vertical-align:-3.13504pt" version="1.1" viewbox="0 0 15.0375 10.925" width="15.0375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.925)"> <g transform="translate(72,-63.26)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,63.31)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> </g> </g> </svg>增加了5% (Lewis肺癌carinoma)</td> </tr> </tbody> </table></strong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(b)增加了5% (Lewis肺癌carinoma)" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/figures/790721.fig.005b.jpg"> <br> <strong> <table> <tbody> <tr> <td><b>(b)</b> <svg height="10.7375" id="M172" style="vertical-align:-0.13794pt" version="1.1" viewbox="0 0 7.9875002 10.7375" width="7.9875002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.7375)"> <g transform="translate(72,-63.41)"> <text transform="matrix(1,0,0,-1,-71.95,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>增加了5% (Lewis肺癌carinoma)</td> </tr> </tbody> </table></strong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-d7a0a0bb065f381ae246c4a152ac8b60 partial-carousel-thumbnail"> <button aria-label="Slide to (a) 𝛼 1 increased by 5% (Lewis lung carinoma)" class="partial-carousel-dot"><img loading="lazy" alt="(1)增加了5% (Lewis肺癌carinoma)" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/thumbnails/790721.fig.005a_th.jpg"><br><strong> <table> <tbody> <tr> <td><b>(一)</b> <svg height="10.925" id="M171" style="vertical-align:-3.13504pt" version="1.1" viewbox="0 0 15.0375 10.925" width="15.0375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.925)"> <g transform="translate(72,-63.26)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,63.31)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> </g> </g> </svg>增加了5% (Lewis肺癌carinoma)</td> </tr> </tbody> </table></strong></button> <button aria-label="Slide to (b) 𝛿 increased by 5% (Lewis lung carinoma)" class="partial-carousel-dot"><img loading="lazy" alt="(b)增加了5% (Lewis肺癌carinoma)" src="https://static.hindawi.com/articles/cmmm/volume-2011/790721/thumbnails/790721.fig.005b_th.jpg"><br><strong> <table> <tbody> <tr> <td><b>(b)</b> <svg height="10.7375" id="M172" style="vertical-align:-0.13794pt" version="1.1" viewbox="0 0 7.9875002 10.7375" width="7.9875002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.7375)"> <g transform="translate(72,-63.41)"> <text transform="matrix(1,0,0,-1,-71.95,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> </text> </g> </g> </svg>增加了5% (Lewis肺癌carinoma)</td> </tr> </tbody> </table></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-d7a0a0bb065f381ae246c4a152ac8b60 partial-carousel-next-prev"> <button aria-label="Previous" class="carousel-prev"></button> <button aria-label="Next" class="carousel-next"></button> </div> </div> </div> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">图5</span> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/cmmm/2011/790721/fig5/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>获得的肿瘤体积增加了5%(一个)<svg height="15.75" id="M169" style="vertical-align:-3.13504pt" version="1.1" viewbox="0 0 15.0375 15.75" width="15.0375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> </g> </g> </svg>和(b)<svg height="13.675" id="M170" style="vertical-align:-0.17555pt" version="1.1" viewbox="0 0 7.9875002 13.675" width="7.9875002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.675)"> <g transform="translate(72,-61.06)"> <text transform="matrix(1,0,0,-1,-65.93,63.97)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.02" y="2.72"> </tspan> </text> </g> </g> </svg>对于路易斯肺癌。</td> </tr> </tbody> </table> </div> </div> </div> </div> <p>正如前面所提到的,我们的模型假设是通过调整标准化和颞目标之间的相互作用被森古普塔et al。<一个href="#B19">19</一个>可以实现一种改进的治疗结果。来验证这个假设,我们建模的不同发布概要文件的纳米细胞核心延迟化疗的分泌相对比发布概要文件被认为是抗血管新生疗法进一步实验的森古普塔et al。<一个href="#B19">19</一个>)(见部分<一个href="#sec3">3</一个>)。我们小心地调整推迟发布概要文件,这样的治疗相同的抗血管新生总数和化疗药物的联合疗法被释放,L (CD)和数控(CD),认为之前。因此,相比传统的纳米细胞疗法,与我们的修改发布概要文件更多的化疗药物释放的纳米细胞接种在早期,但相应地减少化疗药物释放的纳米细胞在稍后的时间管理。</p><p>的仿真结果表明,调整后的释放动力学大幅改善的效果可以实现纳米细胞治疗(见黑色的曲线在图<一个href="//www.newsama.com/journals/cmmm/2011/790721/fig2/" target="_blank">2</一个>)。如图<一个href="//www.newsama.com/journals/cmmm/2011/790721/fig3/" target="_blank">3</一个>,这改进的结果是由于正常化的组合,主要有效的早期阶段的治疗和增加分数纳米细胞传递到肿瘤组织在早期,抗血管新生疗法引起的血管关闭,减少了部分纳米细胞后交货时间和陷阱的化疗药物在肿瘤组织内。我们修改发布概要文件利用这两个效果和带来更好的纳米细胞在肿瘤组织之间的协调和反血管增生和化疗药物的释放。因此,我们的模拟表明,通过明智的正常化的时机和化疗药物在肿瘤组织的捕获通过combretastatin的释放,可以实现更好的治疗结果。</p><p>总之,数学模型可以用来模拟各种治疗方案和援助在假设检验在“网上”,反过来指导实验研究。非常成功的实验结果后森古普塔et al。<一个href="#B19">19</一个>)和实验和临床研究肿瘤血管的正常化过程(<一个href="#B21">10</一个>- - - - - -- - - - - -- - - - - -- - - - - -- - - - - -- - - - - -<一个href="#B23">12</一个>),我们已经建立了一个数学公式,抓住了定性森古普塔和同事提出的照片。这个模型的基础上,我们发现纳米细胞治疗的显著提高治疗效果证明了森古普塔et al。<一个href="#B19">19</一个>主要结果捕获的化疗药物,而不是增加纳米细胞的数量交付给肿瘤通过规范化。此外,我们发现,通过调整释放动力学的化疗可以大幅提高纳米细胞治疗的疗效。由于我们的前途的计算结果,显然需要更多的实验和临床前数据进一步验证这一策略改善治疗结果。特别是,我们的模型结果表明,纳米细胞的分泌有更长的延迟化疗相比,相对于抗血管新生疗法(发布概要文件被认为是森古普塔的实验等。<一个href="#B19">19</一个>)可能会进一步提高处理的效率。我们计算的方法也可以用来设计纳米细胞其他类型的癌症,并定量地确定承诺发布概要文件。</p><h4我d="appendix">附录</h4><p>在本附录我们调查的影响模型参数的值的变化在我们的模型预测。研究参数的敏感性,我们计算的影响参数的微小变化对最终肿瘤体积(在一天17)。我们确定最后肿瘤体积变化百分比估计模型参数摄动时的值5% (<一个href="#B4">25</一个>]。图<一个href="//www.newsama.com/journals/cmmm/2011/790721/fig4/" target="_blank">4</一个>显示的结果联合疗法的情况下使用纳米细胞和脂质体,也就是说,数控(CD)和L (CD)在肺癌。每个人都应该注意,改变<svg height="17.049999" id="M173" style="vertical-align:-0.20064pt;width:91.662498px;" version="1.1" viewbox="0 0 91.662498 17.049999" width="91.662498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,17.05)"> <g transform="translate(72,-58.36)"> <text transform="matrix(1,0,0,-1,-65.69,61.34)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.2600002" y="2.73"> </tspan> </text> <text transform="matrix(1,0,0,-1,-65.19,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="8.7870083" y="0"> )</tspan> </text> <text transform="matrix(1,0,0,-1,-49.51,58.61)"> <tspan style="font-size: 12.50px; " x="37.049999" y="-2.73"> ̃</tspan> <tspan style="font-size: 12.50px; " x="30.790001" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="0" y="0"> =</tspan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 1</tspan> <tspan style="font-size: 12.50px; " x="18.279387" y="0"> 0</tspan> <tspan style="font-size: 12.50px; " x="24.530886" y="0"> 0</tspan> </text> <text transform="matrix(1,0,0,-1,-11.96,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> (</tspan> <tspan style="font-size: 8.75px; " x="2.9144161" y="0"> </tspan> <tspan style="font-size: 8.75px; " x="9.828496" y="0"> )</tspan> </text> </g> </g> </svg>有同样的效果是不同的吗<svg height="13.675" id="M174" style="vertical-align:-0.17555pt;width:7.9875002px;" version="1.1" viewbox="0 0 7.9875002 13.675" width="7.9875002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.675)"> <g transform="translate(72,-61.06)"> <text transform="matrix(1,0,0,-1,-65.93,63.97)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.02" y="2.72"> </tspan> </text> </g> </g> </svg>;此外,该参数<svg height="12" id="M175" style="vertical-align:-0.17555pt;width:8.9375px;" version="1.1" viewbox="0 0 8.9375 12" width="8.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,12)"> <g transform="translate(72,-62.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> </g> </g> </svg>,<svg height="16.362499" id="M176" style="vertical-align:-2.29482pt;width:8.8500004px;" version="1.1" viewbox="0 0 8.8500004 16.362499" width="8.8500004" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,16.3625)"> <g transform="translate(72,-58.91)"> <text transform="matrix(1,0,0,-1,-65.59,63.97)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.3600001" y="2.72"> </tspan> </text> </g> </g> </svg>,<svg height="13.0125" id="M177" style="vertical-align:-2.34499pt;width:8.0625px;" version="1.1" viewbox="0 0 8.0625 13.0125" width="8.0625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.0125)"> <g transform="translate(72,-61.59)"> <text transform="matrix(1,0,0,-1,-65.9,63.97)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.038949" y="0"> </tspan> </text> </g> </g> </svg>并不像他们负责改变血管网络的创建(见正文)。结果表明,参数<svg height="15.75" id="M178" style="vertical-align:-3.13504pt;width:15.0375px;" version="1.1" viewbox="0 0 15.0375 15.75" width="15.0375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> </g> </g> </svg>和<svg height="13.675" id="M179" style="vertical-align:-0.17555pt;width:7.9875002px;" version="1.1" viewbox="0 0 7.9875002 13.675" width="7.9875002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.675)"> <g transform="translate(72,-61.06)"> <text transform="matrix(1,0,0,-1,-65.93,63.97)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.02" y="2.72"> </tspan> </text> </g> </g> </svg>最后肿瘤体积有极大的帮助;然而,这些贡献较小的L (CD)相比,数控(CD)。</p><p>调查是否从我们获得的趋势模型对不同治疗方法对健壮模型参数的变化,我们的使用参数化模型进行了数值模拟<svg height="15.75" id="M180" style="vertical-align:-3.13504pt;width:15.0375px;" version="1.1" viewbox="0 0 15.0375 15.75" width="15.0375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.75)"> <g transform="translate(72,-59.4)"> <text transform="matrix(1,0,0,-1,-71.93,62.57)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </tspan> <tspan style="font-size: 12.50px; " x="-0.012503" y="0"> </tspan> </text> <text transform="matrix(1,0,0,-1,-64.9,59.45)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</tspan> </text> </g> </g> </svg>或<svg height="13.675" id="M181" style="vertical-align:-0.17555pt;width:7.9875002px;" version="1.1" viewbox="0 0 7.9875002 13.675" width="7.9875002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.675)"> <g transform="translate(72,-61.06)"> <text transform="matrix(1,0,0,-1,-65.93,63.97)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ̃</tspan> <tspan style="font-size: 12.50px; " x="-6.02" y="2.72"> </tspan> </text> </g> </g> </svg>是增加了5%,而所有其他模型参数是固定的。如图<一个href="//www.newsama.com/journals/cmmm/2011/790721/fig5/" target="_blank">5</一个>,这些变化不影响趋势见图<一个href="//www.newsama.com/journals/cmmm/2011/790721/fig2/" target="_blank">2(一个)</一个>。</p><h4我d="acknowledgments">确认</h4><p>作者感谢g . Powathil评论手稿。m . Kohandel和美国Sivaloganathan承认金融支持由加拿大自然科学和工程研究理事会(NSERC)和加拿大卫生研究院的研究(CIHR)。c . a . Haselwandter欧文薛定谔在麻省理工学院的奖学金支持奥地利科学基金,支持和m . 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Kohandel et al。这是一个开放的分布式下文章<一个rel="license" href="http://creativecommons.org/licenses/by/3.0/">知识共享归属许可</一个>,它允许无限制的使用、分配和复制在任何媒介,提供最初的工作是正确引用。</div> <div id="related-articles"></div> </div> </div> <div class="ant-col ThreeColumnLayout_rightColumn__b_MuL"> <div> <div> <div class="ArticleRightSection_articleRightSection__rG8Zh"> <div class="ArticleToolbar_articleToolbar__8fsAH"> <a href="https://downloads.hindawi.com/journals/cmmm/2011/790721.pdf" class="ButtonGroup_buttonGroupWrapper__Rqhy0" role="button" type="primary" aria-label="PDF" tabindex="0" unselectable="on" target="_blank" data-testid="download-pdf"><span class="ButtonGroup_leftGroup__FJAmS"><span role="img" class="anticon ButtonGroup_buttonGroupWrapperIcon__CFikg"> <svg xmlns="http://www.w3.org/2000/svg" width="1em" height="1em" viewbox="0 0 19 24"> <path 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