Effect of p53 Gene Transfer and Cisplatin in a Peritonitis Carcinomatosa Model with p53-Deficient Ovarian Cancer Cells

作者: Junzo Kigawa , Shinya Sato , Muneaki Shimada , Yasunobu Kanamori , Hiroaki Itamochi

DOI: 10.1006/GYNO.2001.6488

关键词: Cancer researchIntraperitoneal injectionMedicinePathologyTransfectionSevere combined immunodeficiencyOvarian cancerTumor suppressor geneCisplatinGenetic enhancementPeritonitis

摘要: Abstract Objective. To determine whether combination treatment consisting of p53 gene transfer and cisplatin (CDDP) improves prognosis ovarian cancer patients with peritonitis carcinomatosa, we tried this therapy in a carcinomatosa model that developed. Methods. A human adenocarcinoma cell line, HRA, which has homozygous deletion the gene, was used. For transfection, used recombinant adenovirus carrying wild-type (AxCAp53). efficiency to transduce HRA cells, cells were infected AxCALacZ, transduced detected by β-galactosidase staining. The expression protein monitored Western blot analysis up 15 days after infection 50 MOI AxCAp53. effect AxCAp53 CDDP evaluated 3-(4, 5-dimethelthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Apoptotic assessed morphologically staining Hoechst 33258. study, severe combined immunodeficiency mice an intraperitoneal injection cells. Results. expressed at 24 h disappeared on 14th day. present vitro study showed transduction significantly enhanced sensitivity apoptotic index significant survival advantage observed compared single treatments. However, repetitious did not show long term. Conclusion. suggests is potentially useful as adjuvant therapeutic modality for although further needed improve long-term those patients.

参考文章(20)
Raymond P. Perez, Thomas C. Hamilton, Robert F. Ozols, Robert C. Young, Mechanisms and modulation of resistance to chemotherapy in ovarian cancer. Cancer. ,vol. 71, pp. 1571- 1580 ,(1993) , 10.1002/CNCR.2820710424
D. J. FINNEY, Statisical logic in the monitoring of reactions to therapeutic drugs. Methods of Information in Medicine. ,vol. 10, pp. 237- 245 ,(1971) , 10.1055/S-0038-1636052
Kyuya Ishibiki, Takao Inada, Fumiki Asanuma, Tetsuro Kubota, Osahiko Abe, Munehiko Nakada, Ken Tsuyuki, Cell kinetics and chemosensitivity of human carcinomas serially transplanted into nude mice. Japanese Journal of Cancer Research. ,vol. 77, pp. 502- 507 ,(1986) , 10.20772/CANCERSCI1985.77.5_502
Claudia Caserini, Marco A. Pierotti, Monica Giarola, Rosanna Supino, Paola Perego, Sabina C. Righetti, Franco Zunino, Domenico Delia, John C. Reed, Toshiyuki Miyashita, Association between Cisplatin Resistance and Mutation of p53 Gene and Reduced Bax Expression in Ovarian Carcinoma Cell Systems Cancer Research. ,vol. 56, pp. 556- 562 ,(1996)
Matthew P. Boente, Jean Hurteau, Gustavo C. Rodriguez, Robert C. Bast, Andrew Berchuck, The biology of ovarian cancer Current Opinion in Oncology. ,vol. 5, pp. 900- 907 ,(1993) , 10.1097/00001622-199309000-00020
J.T. Thigpen, K. Bertelsen, E.A. Eisenhauer, N.F. Hacker, B. Lund, C. Sessa, Long-term follow-up of patients with advanced ovarian carcinoma treated with chemotherapy Annals of Oncology. ,vol. 4, pp. 35- 40 ,(1993) , 10.1093/ANNONC/4.SUPPL_4.S35
M Shimada, J Kigawa, Y Kanamori, H Itamochi, M Takahashi, S Kamazawa, S Sato, N Terakawa, Mechanism of the combination effect of wild-type TP53 gene transfection and cisplatin treatment for ovarian cancer xenografts. European Journal of Cancer. ,vol. 36, pp. 1869- 1875 ,(2000) , 10.1016/S0959-8049(00)00161-1
Dao M. Nguyen, Francis R. Spitz, Nancy Yen, Richard J. Cristiano, Jack A. Roth, Gene therapy for lung cancer: Enhancement of tumor suppression by a combination of sequential systemic cisplatin and adenovirus-mediated p53 gene transfer☆☆☆★★★♢♢♢ The Journal of Thoracic and Cardiovascular Surgery. ,vol. 112, pp. 1372- 1377 ,(1996) , 10.1016/S0022-5223(96)70154-X
Makoto Okada, Junzo Kigawa, Yukihisa Minagawa, Yasunobu Kanamori, Hiroaki Itamochi, Xiusi Cheng, Tetsuro Ohishi, Naoki Terakawa, Alterations of theTP53 gene and TP53 protein expression in epithelial ovarian cancer before and after chemotherapy International Journal of Clinical Oncology. ,vol. 3, pp. 240- 246 ,(1998) , 10.1007/BF02489840
Vivian E. von Gruenigen, Joseph T. Santoso, Robert L. Coleman, Carolyn Y. Muller, David Scott Miller, J.Michael Mathis, In vivo studies of adenovirus-based p53 gene therapy for ovarian cancer Gynecologic Oncology. ,vol. 69, pp. 197- 204 ,(1998) , 10.1006/GYNO.1998.5010