Sensitivity Test of Chemotherapy on Human Colorectal Cancer in Vivo_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHEN Yunhuan ¹ ,  YAN Dengguo ¹ , ZHANG Dongxing ² , LI Guosheng ¹ , GONG Hui ¹

1.Department of Anus and Intestine Surgery， Affiliated Hospital of Guiyang Medical College， Guiyang 550004， Guizhou Province， China;;
2.Department of General Surgery， The People’s Hospital of Guizhou Province， Guiyang 550001， Guizhou Province， China;

Corresponding author：

YAN Dengguo, Email: dengguoy@163.com

Keywords：

Colorectal cancer; Chemotherapy; Sensitivity; In vivo experiment

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Objective 　To investigate the sensitivity of 5 kinds of chemotherapeutic drugs on human colorectal cancer in vivo.
Methods 　Xenografts in nude mice were set up by tumor tissues from 9 patients with colorectal cancer and nude mice were divided into 6 groups randomly， receiving saline （control group）， 5-fluorouracil （5-FU group）， doxorubicin
（ADM group）， mitomycin （MMC group）， oxaliplatin （LOHP group）， and irinotecan （CPT-11 group）， respectively. The inhibitive rates （IR） of xenografts in 5 groups for each patient were calculated.
Results 　The lowest and highest IR of 5 groups were 23.6% and 54.9% in 5-FU group， 23.7% and 69.5% in LOPH group， 23.6% and 82.6% in CPT-11
group， 24.1% and 48.1% in MMC group， 5.8% and 20.7% in ADM group， respectively. The IR exceeded 40.0% in 7 patients of LOHP group， 6 patients of CPT-11 group， 4 patients of 5-FU group， and 1 patient of MMC group， respec-
tively. Of 9 patients， the IR exceeded 40.0% to 3 kinds of drugs in 3 patients， to 2 kinds of drugs in 4 patients， the IR didn’t exceed 30.0% to 4 kinds of drug （IR was 82.6% to CPT-11） in 1 patient， and the IR didn’t exceed 31.0% to all 5 kinds of drugs in 1 patient. There were statistical differences on the IR of 5 kinds of drugs （H=24.061 2， P=0.000 1）. IR of ADM group was statistical lower than 5-FU group， MMC group， LOHP group， and CPT-11 group （P＜0.05），but there were no statistical differences between 5-FU group， MMC group， LOHP group， and CPT-11 group （P＞0.05）.
Conclusions 　The xenografts from same patient have different sensitivity to different chemotherapy drugs， and the same chemotherapy drug corresponds to different IR in different patients. The IR of LOHP and CPT-11 are the highest， following by 5-FU and MMC.

Citation： ZHEN Yunhuan,YAN Dengguo,ZHANG Dongxing,LI Guosheng,GONG Hui. Sensitivity Test of Chemotherapy on Human Colorectal Cancer in Vivo. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(1): 48-53. doi: Copy

1.	Underhill C， Goldstein D， Gorbounova VA， et al. A randomized phaseⅡtrial of pemetrexed plus irinotecan (ALIRI) versus leucovorin-modulated 5-FU plus irinotecan (FOLFIRI) in first-line treatment of locally advanced or metastatic colorectal cancer[J]. Oncology， 2007， 73(1-2)：9-20.
2.	Scalamogna R， Brugnatelli S， Tinelli C， et al. UFT as maintenance therapy in patients with advanced colorectal cancer responsive to the FOLFOX4 regimen[J]. Oncology， 2007， 72(5-6)：267-273.
3.	Satram-Hoang S， Lee L， Yu S， et al. Comparative effectiveness of chemotherapy in elderly patients with metastatic colorectal cancer[J]. J Gastrointest Cancer， 2012， [Epub ahead of print].
4.	Mccleary NJ， Odejide O， Szymonifka J， et al. Safety and effecti-veness of oxaliplatin-based chemotherapy regimens in adults 75 years and older with colorectal cancer[J]. Clin Colorectal Cancer，2012， [Epub ahead of print].
5.	Focan C， Kreutz F， Graas MP， et al. Phase Ⅰ-Ⅱ study to assess the feasibility and activity of the triple combination of 5-fluorouracil/folinic acid， carboplatin and irinotecan (CPT-11) administered by chronomodulated infusion for the treatment of advanced colorectal cancer. Final report of the BE-1603 study[J]. Pathol Biol (Paris)， 2012， [Epub ahead of print].
6.	张洪伟，同李平，孙力. 结直肠癌的个体化治疗进展[J]. 中国普外基础与临床杂志， 2009， 16(9)：689-692.
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9.	Tohyama N， Tanaka S， Onda K， et al. Influence of anticancer agents on cell survival， proliferation， and CD4＋CD25＋Foxp3＋ regulatory T cell-frequency in human peripheral-blood mononuclear cells activated by T cell-mitogen[J]. Int Immunopharmacol，2012， [Epub ahead of print].
10.	Adachi W， Sugenoya A， Horigome N， et al. The antitumor activityand immunosuppressive effects of 5-fluorouracil suppositories in rectal cancer patients[J]. Surg Today， 1992， 22(3)：221-225.
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14.	马望，王留兴，王瑞林，等. 胰岛素增强5-氟尿嘧啶对体外结肠癌细胞的细胞毒作用[J]. 中华肿瘤杂志， 2010， 32(3)：169-172.
15.	周进明，钟大平，周琪，等. 地塞米松影响结肠癌细胞对奥沙利铂和氟尿嘧啶化疗敏感性的实验研究[J]. 中国肿瘤临床， 2010， 37(3)：142-145.
16.	姚祺，李太原. 大肠癌细胞体外培养药敏试验与临床特征关系探讨[J]. 实用癌症杂志， 2006， 21(6)：564-566.
17.	Kim JH， Kim HS， Choi DR， et al. A phaseⅡstudy of mitomycin-C and S-1 as third-line chemotherapy in patients with advanced colorectal cancer[J]. Oncol Lett， 2011， 2(6)：1253-1256.
18.	Voigt W， Behrmann C， Schlueter A， et al. A new chemoemboliz-ation protocol in refractory liver metastasis of colorectal cancer—a feasibility study[J]. Onkologie， 2002， 25(2)：158-164.
19.	Ducreux M， Raoul JL， Marti P， et al. High-dose irinotecan plus LV5FU2 or simplified LV5FU (HD-FOLFIRI) for patients withuntreated metastatic colorectal cancer：a new way to allow resection of liver metastases?[J]. Oncology， 2008， 74(1-2)：17-24.
20.	Yu DS， Li Y， Huang XE， et al. Effect of portal vein chemotherapy on liver metastasis after surgical resection of colorectal cancer[J]. Asian Pac J Cancer Prev， 2012， 13(9)：4699-4701.
21.	Ono T， Ishida H， Kumamoto K， et al. Outcome in disappearing colorectal cancer liver metastases during oxaliplatin-based chemotherapy[J]. Oncol Lett， 2012， 4(5)：905-909.
22.	Kataoka K， Kanazawa A， Nakajima A， et al. The feasibility and potential benefit of preoperative chemotherapy for colorectal liver metastasis (CLM)：a single-centered retrospective study[J]. Surg Today， 2012， [Epub ahead of print].
23.	Deboever G， Hiltrop N， Cool M， et al. Alternative treatment opti-ons in colorectal cancer patients with 5-Fluorouracil-or capecitabine-induced cardiotoxicity[J]. Clin Colorectal Cancer， 2012， [Epub ahead of print].
24.	Mishra J， Drummond J， Quazi SH， et al. Prospective of colon can-cer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis[J]. Crit Rev Oncol Hematol， 2012， [Epub ahead of print].
25.	Mishima H， Ikenaga M， Yasui M. Safety and efficacy of FOLFOX and FOLFIRI in elderly patients with colorectal cancer[J]. Nihon Rinsho， 2011， 69 Suppl 3：554-558.
26.	Kline CL， Sheikh HS， Scicchitano A， et al. Preliminary observations indicate variable patterns of plasma 5-fluorouracil (5-FU) levels during dose optimization of infusional 5-FU in colorectal cancer patients[J]. Cancer Biol Ther， 2011， 12(7)：557-568.
27.	de Melo JV， Vieira de Melo MS， Abad MH. Clinical and radiological response with FOLFOXIRI and bevacizumab as third-line therapy after mFOLFOX6 and FOLFIRI failure[J]. Anticancer Drugs， 2011， 22 Suppl 2：S19-S20.

1. Underhill C， Goldstein D， Gorbounova VA， et al. A randomized phaseⅡtrial of pemetrexed plus irinotecan (ALIRI) versus leucovorin-modulated 5-FU plus irinotecan (FOLFIRI) in first-line treatment of locally advanced or metastatic colorectal cancer[J]. Oncology， 2007， 73(1-2)：9-20.
2. Scalamogna R， Brugnatelli S， Tinelli C， et al. UFT as maintenance therapy in patients with advanced colorectal cancer responsive to the FOLFOX4 regimen[J]. Oncology， 2007， 72(5-6)：267-273.
3. Satram-Hoang S， Lee L， Yu S， et al. Comparative effectiveness of chemotherapy in elderly patients with metastatic colorectal cancer[J]. J Gastrointest Cancer， 2012， [Epub ahead of print].
4. Mccleary NJ， Odejide O， Szymonifka J， et al. Safety and effecti-veness of oxaliplatin-based chemotherapy regimens in adults 75 years and older with colorectal cancer[J]. Clin Colorectal Cancer，2012， [Epub ahead of print].
5. Focan C， Kreutz F， Graas MP， et al. Phase Ⅰ-Ⅱ study to assess the feasibility and activity of the triple combination of 5-fluorouracil/folinic acid， carboplatin and irinotecan (CPT-11) administered by chronomodulated infusion for the treatment of advanced colorectal cancer. Final report of the BE-1603 study[J]. Pathol Biol (Paris)， 2012， [Epub ahead of print].
6. 张洪伟，同李平，孙力. 结直肠癌的个体化治疗进展[J]. 中国普外基础与临床杂志， 2009， 16(9)：689-692.
7. Rayson D， Urquhart R， Cox M， et al. Adherence to clinical practice guidelines for adjuvant chemotherapy for colorectal cancer in a Canadian province：a population-based analysis[J]. J Oncol Pract， 2012， 8(4)：253-259.
8. Oyan B. Why do targeted agents not work in the adjuvant settingin colon cancer?[J] . Expert Rev Anticancer Ther， 2012， 12(10)：1337-1345.
9. Tohyama N， Tanaka S， Onda K， et al. Influence of anticancer agents on cell survival， proliferation， and CD4＋CD25＋Foxp3＋ regulatory T cell-frequency in human peripheral-blood mononuclear cells activated by T cell-mitogen[J]. Int Immunopharmacol，2012， [Epub ahead of print].
10. Adachi W， Sugenoya A， Horigome N， et al. The antitumor activityand immunosuppressive effects of 5-fluorouracil suppositories in rectal cancer patients[J]. Surg Today， 1992， 22(3)：221-225.
11. Maeda K， Hazama S， Tokuno K， et al. Impact of chemotherapy for colorectal cancer on regulatory T-cells and tumor immunity[J]. Anticancer Res， 2011， 31(12)：4569-4574.
12. 张东兴，颜登国，赵丙波. 人大肠癌裸鼠皮下移植瘤模型的建立[J]. 贵阳医学院学报， 2010， 35(3)：247-250.
13. 韩杰，檀碧波，吕炳蓉，等. 胃癌与大肠癌原代细胞培养化疗药物敏感性的对比[J]. 中华普通外科杂志， 2008， 23(6)：464-465.
14. 马望，王留兴，王瑞林，等. 胰岛素增强5-氟尿嘧啶对体外结肠癌细胞的细胞毒作用[J]. 中华肿瘤杂志， 2010， 32(3)：169-172.
15. 周进明，钟大平，周琪，等. 地塞米松影响结肠癌细胞对奥沙利铂和氟尿嘧啶化疗敏感性的实验研究[J]. 中国肿瘤临床， 2010， 37(3)：142-145.
16. 姚祺，李太原. 大肠癌细胞体外培养药敏试验与临床特征关系探讨[J]. 实用癌症杂志， 2006， 21(6)：564-566.
17. Kim JH， Kim HS， Choi DR， et al. A phaseⅡstudy of mitomycin-C and S-1 as third-line chemotherapy in patients with advanced colorectal cancer[J]. Oncol Lett， 2011， 2(6)：1253-1256.
18. Voigt W， Behrmann C， Schlueter A， et al. A new chemoemboliz-ation protocol in refractory liver metastasis of colorectal cancer—a feasibility study[J]. Onkologie， 2002， 25(2)：158-164.
19. Ducreux M， Raoul JL， Marti P， et al. High-dose irinotecan plus LV5FU2 or simplified LV5FU (HD-FOLFIRI) for patients withuntreated metastatic colorectal cancer：a new way to allow resection of liver metastases?[J]. Oncology， 2008， 74(1-2)：17-24.
20. Yu DS， Li Y， Huang XE， et al. Effect of portal vein chemotherapy on liver metastasis after surgical resection of colorectal cancer[J]. Asian Pac J Cancer Prev， 2012， 13(9)：4699-4701.
21. Ono T， Ishida H， Kumamoto K， et al. Outcome in disappearing colorectal cancer liver metastases during oxaliplatin-based chemotherapy[J]. Oncol Lett， 2012， 4(5)：905-909.
22. Kataoka K， Kanazawa A， Nakajima A， et al. The feasibility and potential benefit of preoperative chemotherapy for colorectal liver metastasis (CLM)：a single-centered retrospective study[J]. Surg Today， 2012， [Epub ahead of print].
23. Deboever G， Hiltrop N， Cool M， et al. Alternative treatment opti-ons in colorectal cancer patients with 5-Fluorouracil-or capecitabine-induced cardiotoxicity[J]. Clin Colorectal Cancer， 2012， [Epub ahead of print].
24. Mishra J， Drummond J， Quazi SH， et al. Prospective of colon can-cer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis[J]. Crit Rev Oncol Hematol， 2012， [Epub ahead of print].
25. Mishima H， Ikenaga M， Yasui M. Safety and efficacy of FOLFOX and FOLFIRI in elderly patients with colorectal cancer[J]. Nihon Rinsho， 2011， 69 Suppl 3：554-558.
26. Kline CL， Sheikh HS， Scicchitano A， et al. Preliminary observations indicate variable patterns of plasma 5-fluorouracil (5-FU) levels during dose optimization of infusional 5-FU in colorectal cancer patients[J]. Cancer Biol Ther， 2011， 12(7)：557-568.
27. de Melo JV， Vieira de Melo MS， Abad MH. Clinical and radiological response with FOLFOXIRI and bevacizumab as third-line therapy after mFOLFOX6 and FOLFIRI failure[J]. Anticancer Drugs， 2011， 22 Suppl 2：S19-S20.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Sensitivity Test of Chemotherapy on Human Colorectal Cancer in Vivo

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