Evaluation of chemosensitivity prediction using quantitative dose–response curve classification for highly advanced/relapsed gastric cancer

World Journal of Surgical Oncology

Research

Go Wakabayashi¹  Keisuke Koeda¹  Hirokatsu Katagiri²  Teppei Matsuo²  Fumitaka Endo²  Kazushige Ishida²  Miyuki Ikeda²  Kohei Kume³  Satoshi S Nishizuka³ 

[1]Department of Surgery Iwate Medical University School of Medicine, 19-1 Uchimaru, 020-8505, Morioka, Iwate, Japan

[2]MIAST (Medical Innovation by Advanced Science and Technology) Program, Iwate Medical University School of Medicine, 19-1 Uchimaru, 020-8505, Morioka, Iwate, Japan

[3]Laboratory of Molecular Therapeutics Iwate Medical University School of Medicine, 19-1 Uchimaru, 020-8505, Morioka, Iwate, Japan

[4]Department of Surgery Iwate Medical University School of Medicine, 19-1 Uchimaru, 020-8505, Morioka, Iwate, Japan

[5]Laboratory of Molecular Therapeutics Iwate Medical University School of Medicine, 19-1 Uchimaru, 020-8505, Morioka, Iwate, Japan

[6]Department of Surgery Iwate Medical University School of Medicine, 19-1 Uchimaru, 020-8505, Morioka, Iwate, Japan

[7]MIAST (Medical Innovation by Advanced Science and Technology) Program, Iwate Medical University School of Medicine, 19-1 Uchimaru, 020-8505, Morioka, Iwate, Japan

[8]Institute for Biomedical Sciences, Iwate Medical University, 2-1-1 Nishitokuta, 028-3694, Yahaba, Iwate, Japan

关键词: Gastric cancer;    Chemosensitivity;    Dose–response curves;    Ascites;   

DOI  :  10.1186/1477-7819-11-11

 received in 2012-09-01, accepted in 2013-01-06,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundThe use of standard chemotherapy regimens has changed the application of chemosensitivity tests from all chemotherapy-eligible patients to those who have failed standard chemotherapy, which includes patients with highly advanced, relapsed, or chemoresistant tumors.MethodsWe evaluated a total of 43 advanced primary and relapsed gastric cancers for chemosensitivity based on drug dose response curves to improve the objectivity and quality of quantitative measurements. The dose response curves were classified based on seven expected patterns. Instead of a binary chemosensitivity evaluation, we ranked drug sensitivity according to curve shapes and comparison with the peak plasma concentration (ppc) of each drug.ResultsA total of 193 dose response curves were obtained. The overall informative rate was 67.4%, and 85.3% for cases that had a sufficient number of cells. Paclitaxel (PXL)and docetaxel tended to show a higher rank, while cisplatin (CIS) and 5-fluorouracil (5-FU) tended to show resistance, particularly among the 20 cases (46.5%) that had recurrent disease after receiving chemotherapy with CIS and S-1 (5-FU). As such, we speculate that the resistant pattern of the chemosensitivity test suggests that cells with acquired drug resistance were selected by chemotherapy. Indeed, we observed a change in the chemosensitivity pattern of a sample before and after chemotherapy in terms of PXL sensitivity, which was used after primary chemotherapy.ConclusionsThese results suggest that: (i) the dose–response pattern provides objective information for predicting chemosensitivity; and (ii) chemotherapy may select resistant cancer cell populations as a result of the therapy.

【 授权许可】

Unknown   
© Matsuo et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.