Feasibility of administering human pancreatic cancer chemotherapy in a spontaneous pancreatic cancer mouse model.
Feasibility of administering human pancreatic cancer chemotherapy in a spontaneous pancreatic cancer mouse model.
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DOI：
10.1186/s12885-022-09255-3
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发表时间：
2022-02-16
期刊：
影响因子：
3.8
通讯作者：
Taniguchi CM
中科院分区：
文献类型：
--
作者：
Delahoussaye AM;Abi Jaoude J;Green M;Fujimoto TN;Molkentine J;Garcia Garcia CJ;Gay JP;Feng N;Marszalek J;Fowlkes N;Taniguchi CM
改良FOLFIRINOX（mFFX）和吉西他滨/nab-紫杉醇化疗方案均已显示可改善胰腺癌患者的临床结局，并且通常可互换使用作为标准治疗。临床前研究通常不使用这些方案，因为管理这些多药方法可能很困难。在这项研究中，我们评估了使用KPC小鼠在自发性胰腺肿瘤中给予这两种化疗方案的可行性，最终目标是推进临床前研究。KPC小鼠是通过将KrasLSL− G12 D/+与Trp 53 fl/fl; Ptf 1 αCre/+交配产生的KrasLSL− G12 D/+; p53 fl/+; Ptf 1 αCre/+小鼠。在14周龄时，触诊小鼠的自发性肿瘤生长，使用超声波进行验证。使用肿瘤直径小于15 mm的小鼠。小鼠被分配到七种治疗方案之一：1个周期的mFFX（FFX X1）、2个周期的mFFX（FFX X2）、1个周期的mFFX +40戈伊SBRT（FFX SBRT）、1个周期的吉西他滨/nab-紫杉醇（GEM/AB X1）、2个周期的吉西他滨/nab-紫杉醇（GEM/AB X2）、2个周期的吉西他滨/nab-紫杉醇+40戈伊SBRT（GEM/AB SBRT）或仅盐水（对照）。总共包括92只小鼠。FFX X2组的中位OS略长于FFX X1组的中位OS（15天vs 11天，P = 0.003）。与GEM/AB X1组小鼠相比，GEM/AB X2组小鼠的OS更长（33.5 vs 13天，P = 0.001）。用化疗处理的小鼠比未处理的对照动物存活更长时间（中位OS：6.5天，P < 0.001）。此外，在接受化疗的小鼠中，接受2个周期GEM/AB X2的小鼠生存期最长，而FFX X1组的OS最差（P < 0.001）。除了CD 4+细胞水平仅在吉西他滨/nab-紫杉醇治疗的肿瘤中基本不变外，化疗的添加与髓样和淋巴样细胞类型数量的减少相关。最后，化疗后巩固SBRT趋向于增加局部控制和生存。我们证明了临床相关的mFOLFIRINOX和吉西他滨/nab-紫杉醇在胰腺癌临床前模型中的实用性和可行性。
Both modified FOLFIRINOX (mFFX) and gemcitabine/nab-paclitaxel chemotherapy regimens have been shown to improve clinical outcomes in patients with pancreatic cancer, and are often used interchangeably as the standard of care. Preclinical studies often do not use these regimens, since administering these multiagent approaches can be difficult. In this study, we assessed the feasibility of administering these two chemotherapy regimens in spontaneous pancreatic tumors using KPC mice with the ultimate goal of advancing preclinical studies. KPC mice were created by breeding KrasLSL−G12D/+ to Trp53fl/fl;Ptf1αCre/+, resulting in KrasLSL−G12D/+;p53fl/+;Ptf1αCre/+ mice. At 14 weeks of age, mice were palpated for spontaneous tumor growth that was verified using ultrasounds. Mice with tumors under 15 mm in diameter were used. The mice were assigned to one of seven treatment regimens: 1 cycle of mFFX (FFX X1), 2 cycles of mFFX (FFX X2), 1 cycle of mFFXwith 40 Gy SBRT (FFX SBRT), 1 cycle of gemcitabine/nab-paclitaxel (GEM/AB X1), 2 cycles of gemcitabine/nab-paclitaxel (GEM/AB X2), 2 cycles of gemcitabine/nab-paclitaxel with 40 Gy SBRT (GEM/AB SBRT), or saline only (control). In total, 92 mice were included. The median OS in the FFX X2 group was slightly longer that the median OS in the FFX X1 group (15 days vs 11 days, P = 0.003). Mice in the GEM/AB X2 group had longer OS when compared to mice in the GEM/AB X1 group (33.5 vs 13 days, P = 0.001). Mice treated with chemotherapy survived longer than untreated control animals (median OS: 6.5 days, P < 0.001). Moreover, in mice treated with chemotherapy, mice that received 2 cycles of GEM/AB X2 had the longest survival, while the FFX X1 group had the poorest OS (P < 0.001). The addition of chemotherapy was associated with reduced number of myeloid and lymphoid cell types, except for CD4 + cells whose levels were largely unaltered only in tumors treated with gemcitabine/nab-paclitaxel. Lastly, chemotherapy followed by consolidative SBRT trended towards increased local control and survival. We demonstrate the utility and feasibility of clinically relevant mFOLFIRINOX and gemcitabine/nab-paclitaxel in preclinical models of pancreatic cancer.
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影响因子：
3.8
作者：
Chun JW;Lee SH;Kim JS;Park N;Huh G;Cho IR;Paik WH;Ryu JK;Kim YT
通讯作者：
Kim YT
DOI：
10.1158/1078-0432.ccr-21-0998
发表时间：
2021-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Peng H;James CA;Cullinan DR;Hogg GD;Mudd JL;Zuo C;Takchi R;Caldwell KE;Liu J;DeNardo DG;Fields RC;Gillanders WE;Goedegebuure SP;Hawkins WG
通讯作者：
Hawkins WG
影响因子：
11.2
作者：
Fujimoto, Tara N.;Colbert, Lauren E.;Taniguchi, Cullen M.
通讯作者：
Taniguchi, Cullen M.
DOI：
10.1016/j.ijrobp.2003.11.004
发表时间：
2004-03-15
影响因子：
7
作者：
Koong, AC;Le, QT;Bastidas, JA
通讯作者：
Bastidas, JA
影响因子：
11.2
作者：
Hinz, Sebastian;Pagerols-Raluy, Laia;Kalthoff, Holger
通讯作者：
Kalthoff, Holger