New chemosensitivity test using a thermo-reversible gelation polymer for recurrent gynecologic cancer patients and a preliminary study of mechanisms of anticancer drug resistance.
OBJECTIVE
TGP (thermo-reversible gelation polymer) is a high molecular compound that has so-gel transmitting temperature of 221C Since solid cancer tissue grows in this polymer three-dimensionally, and fibroblasts scarcely grow in it, TGP is suitable for chemosensitivity assays for solid tumors. In this study, a chemosensitivity test using TGP was applied to recurrent gynecologic cancer patients in order to evaluate its utility and efficacy. In some ovarian cancer cases, expression of anticancer drug resistance-related proteins was also analyzed.


METHODS
Recurrent tumor tissues were surgically obtained with informed consent. After these tissues were minced and incubated for 4 days with CDDP, mitomycin C, 5-fluorouracil, paclitaxel, and CPT-11, the sensitivity against these drugs was estimated. Western blotting was performed in 8 recurrent ovarian cancer tissues in order to analyze the expression of Bcl-2, MRP2, BCRP, and GST-pi.


RESULTS
The total evaluability rate of this assay was 90.6% (29/32). Sensitive drugs could be determined in 5 of 7 ascites samples (71.4%) and in 2 of 3 intra-tumoral fluid samples (66.7%). The overall clinical response rate of chemotherapy determined by these results was 50.0%. There were significant correlations between the IC50 of CDDP and Bcl-2, BCRP, GST-pi, and between that of 5-FU and MRP 2.


CONCLUSIONS
Although this was a preliminary study, the chemosensitivity test using this new material appears to be useful for designing 'made-to order' salvage chemotherapy for pretreated recurrent gynecologic patients. In order to overcome multidrug resistance, the mechanisms of multidrug resistance should be further investigated.
Ohara
Tatsuru
T
Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki-city, Kanagawa, Japan. tatsuru@marianna-u.ac.jp
Kiguchi
Kazushige
K
Tsukikawa
Satoshi
S
Sato
Sojiro
S
Kobayashi
Yoichi
Y
Ishizuka
Bunpei
B
Kubota
Sunao
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D003470:Culture Media; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D005782:Gels; D005833:Genital Neoplasms, Female / Q000473:pathology*; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2; D009364:Neoplasm Recurrence, Local; D011108:Polymers; D013696:Temperature; D014407:Tumor Cells, Cultured
C000715087:ABCC2 protein, human; D000970:Antineoplastic Agents; D003470:Culture Media; D005782:Gels; D000089762:Multidrug Resistance-Associated Protein 2; D011108:Polymers