ABSTRACT
BACKGROUND: It has been shown that IAPs, in particular XIAP, survivin and c-IAP1, are overexpressed in several malignancies. In the present study we investigate the expression of c-IAP1, c-IAP2, XIAP and survivin and its isoforms in cervical cancer. METHODS: We used semiquantitative RT-PCR assays to analyze 41 cancer and 6 normal tissues. The study included 8 stage I cases; 16 stage II; 17 stageIII; and a control group of 6 samples of normal cervical squamous epithelial tissue. RESULTS: c-IAP2 and XIAP mRNA levels were similar among the samples, cervical tumors had lower c-IAP1 mRNA levels. Unexpectedly, a clear positive association was found between low levels of XIAP and disease relapse. A log-rank test showed a significant inverse association (p = 0.02) between XIAP expression and tumor aggressiveness, as indicated by disease relapse rates. There were no statistically significant differences in the presence or expression levels of c-IAP1 and c-IAP2 among any of the clinical variables studied. Survivin and its isoforms were undetectable in normal cervical tissues, in contrast with the clear upregulation observed in cancer samples. We found no association between survivin expression and age, clinical stage, histology or menopausal state. Nevertheless, we found that adenocarcinoma tumors expressed higher levels of survivin 2B and DeltaEx3 (p = 0.001 and p = 0.04 respectively, by Kruskal-Wallis). A multivariate Cox's partial likelihood-based analysis showed that only FIGO stage was an independent predictor of outcome. CONCLUSION: There are no differences in the expression of c-IAP2 and XIAP between normal vs. cancer samples, but XIAP expression correlate in cervical cancer with relapse of this disease in the patients. Otherwise, c-IAP1 was downregulated in the cervical cancer samples. The expression of survivin was upregulated in the patients with cervical cancer. We have found that adenocarcinoma presented higher levels of survivin isoforms 2B and DeltaEx3.
Subject(s)
Inhibitor of Apoptosis Proteins/genetics , Microtubule-Associated Proteins/genetics , Neoplasm Proteins/genetics , Uterine Cervical Neoplasms/metabolism , X-Linked Inhibitor of Apoptosis Protein/genetics , Adenocarcinoma/chemistry , Adenocarcinoma/pathology , Cell Line, Tumor , Female , Humans , Neoplasm Staging , Prognosis , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Survivin , Uterine Cervical Neoplasms/pathologyABSTRACT
Oxaliplatin (cis-[(1R,2R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)-O,O'] platinum; Eloxatin) is a third-generation platinum compound with a 1,2-diaminocyclohexane (DACH) carrier ligand, which has a wide spectrum of anticancer activity in vitro systems and has displayed preclinical and clinical activity in a wide variety of tumors. To investigate its in vitro activity against head and neck cancer, we exposed two head and neck cancer cell lines to the compound, created a variant resistant to cisplatin to study cross-resistance to the compound and analyzed the potential radiosensitizing effect of the drug. We report here that oxaliplatin was cytotoxic at similar doses to cisplatin in these cells. There was no cross-resistance to cisplatin, as demonstrated by different IC50 values in these cell lines and the sensitivity to oxaliplatin of the cisplatin-resistant cell line. There was an effective radiosensitizer effect of the compound in either cell line. Additional in vitro and in vivo experimentation is warranted in order to support the use of oxaliplatin as a radiosensitizer in head and neck cancer patients.
Subject(s)
Antineoplastic Agents/therapeutic use , Head and Neck Neoplasms/drug therapy , Organoplatinum Compounds/therapeutic use , Radiation-Sensitizing Agents/therapeutic use , Cisplatin/therapeutic use , Cross Reactions , Drug Resistance, Neoplasm , Humans , Oxaliplatin , Tumor Cells, CulturedABSTRACT
Objetivo. Realizar un análisis sobre la epidemiología descriptiva de cáncer en el Instituto Nacional de Cancerología de México y sobre las características de la creciente demanda de atención médica. Material y métodos. Se revisó la experiencia de 10 años del Registro Hospitalario de Cáncer en el periodo comprendido entre 1985 y 1994. Resultados. En el periodo de estudio se registraron 28,581 pacientes con confirmación histológica de cáncer. Hubo 8984 (31.4 por ciento) casos en hombres; los tumores más frecuentes fueron en testículo (8.3 por ciento), en pulmón (7.4 por ciento), linfoma no-Hodgkin (7.1 por ciento) y en próstata (5.5 por ciento). Entre las mujeres se presentaron 19597 (68.6 por ciento) casos; el cáncer de cérvix uterino invasor (30.6 por ciento) y el cáncer de mama (20.6 por ciento) representaron más de 50 por ciento del total de pacientes. En 1996 se dieron 108876 consultas; hubo 6492 hospitalizaciones, 36388 sesiones de radioterapia y 9116 administraciones de quimioterapia. Sólo 30 por ciento de la población atendida proviene del Distrito Federal, y la restante reside en los 31 estados de la República. Conclusiones. Es necesario fortalecer los Centros Estatales de Cancerología para la contrarreferencia de pacientes y evitar así la rápida saturación de los servicios médicos de este instituto; así como estimular la creación de registros hospitalarios y colaborar con la Secretaría de Salud para optimizar los programas de detección temprana de cáncer en México