RESUMEN
OBJECTIVE: To investigate the combined effects of cisplatin and the histone deacetylase (HDAC) inhibitors suberoylanilide hydroxamic acid (SAHA) or sirtinol on HeLa cells and assess the mechanism underlying HDAC inhibitor-cisplatin synergy. METHODS: The antineoplastic actions of cisplatin, SAHA and sirtinol, alone and in combination, were evaluated using the tetrazolium dye-based MTT cell proliferation assay, DAPI nuclear staining and cytotoxicity analysis. RESULTS: Exposure to cisplatin, SAHA or sirtinol alone induced a dose-dependent reduction in HeLa cell viability. Combined treatment with cisplatin and SAHA or sirtinol was significantly more cytotoxic than cisplatin alone. Individually, cisplatin, SAHA and sirtinol activated caspase-3 and induced apoptosis, but the effects of combined treatment were greater. Importantly, both HDAC inhibitors dose-dependently inhibited the expression of the antiapoptotic proteins Bcl-2 and x-linked inhibitor of apoptosis protein (XIAP). CONCLUSION: The combination of cisplatin and SAHA or sirtinol had synergistic effect on the HeLa cell viability. This potentiation of cisplatin activity was associated with HDAC inhibitor-mediated down-regulation of Bcl-2 and XIAP. These may result from the relaxation of chromatin by these HDAC inhibitors that increase cisplatin sensitivity by enhancing the accessibility of DNA to cisplatin and transcriptional regulators.
Asunto(s)
Humanos , Apoptosis , Benzamidas , Caspasa 3 , Proliferación Celular , Cromatina , Cisplatino , ADN , Regulación hacia Abajo , Células HeLa , Inhibidores de Histona Desacetilasas , Histona Desacetilasas , Histonas , Ácidos Hidroxámicos , Indoles , Naftoles , Proteínas , Relajación , Neoplasias del Cuello Uterino , Proteína Inhibidora de la Apoptosis Ligada a XRESUMEN
OBJECTIVE: The aim of this study was to evaluate the oncologic and reproductive outcomes of patients with ovarian yolk sac tumor after bleomycin, etoposide, cisplatin (BEP) chemotherapy following surgery. METHODS: Of 145 patients with histologically confirmed malignant ovarian germ cell tumor, 43 had yolk sac tumor and received BEP chemotherapy after surgery. A retrospective analysis of these patients was performed. RESULTS: The mean age of 43 patients was 24.8 years (range, 7 to 59 years). Thirty eight patients were nulliparous. Of 179 BEP chemotherapy cycles, grade 1~2 hematologic and non-hematologic adverse events occurred in 46 cycles in 21 patients. Thirty nine patients showed complete remission, 1 patient showed partial remission, and 3 patient had progressive disease during BEP chemotherapy. After median follow-up time of 57 months (range, 3 to 153 months), 5 patients had recurrent disease and three of them died of disease. The 5-year recurrence free survival rate and overall survival rate were 86% and 94%, respectively. After chemotherapy, all but one premenarchal patients had normal menstruation. Of them 5 patients tried to conceive and 3 of them succeeded in pregnancy. CONCLUSION: BEP chemotherapy was very safe and effective in patients with ovarian yolk sac tumor. Survival outcomes are excellent and reproductive outcomes are promising after BEP chemotherapy.
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Femenino , Humanos , Embarazo , Bleomicina , Cisplatino , Quimioterapia Combinada , Tumor del Seno Endodérmico , Etopósido , Estudios de Seguimiento , Menstruación , Neoplasias de Células Germinales y Embrionarias , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia , Saco VitelinoRESUMEN
This study evaluated the degree and the frequency of cervical lesions after treatment with LEEP(loop electrosurgical excision procedure) in patients with abnormal Pap smears according to the presence or absence of high-risk HPV infection. From June 1994 to May 1997, eighty patients who showed CIN or chronic cervicitis on LEEP specimens were followed up with Pap smears. The histologic results and follow-up Pap smear data were analyzed. In all cases HPV test by Hybrid Capture assay was performed. Those with neoplastic lesion underwent follow-up Pap smears at least for 1 year with 3 month interval after LEEP. In HPV-positive group(N 38), 63.2% of the cases revealed neoplastic lesion(CIN) on final histologic evaluation, and in HPV-negative group(N 42) 54.8% of the cases did(p 0.26). HPV-positive group represented 25.0%(6/24) of abnormal Pap smear result on follow-up, which is higher than that of HPV-negative group(4.3%; 1/23), showing significant difference (p<0.05). There was a significant difference in the rate of neoplastic lesion developed during follow-up between resection margin-positive group and resection margin-negative group on LEEP(p 0,04). Also, HPV-positive group had significantly higher chance to show abnormal Pap smear results during follow-up(p 0.02). In conclusion, HPV test and margin status were shown to be useful parameters to predict the recurrence or persistence of CIN lesion treated by LEEP.
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Humanos , Estudios de Seguimiento , Recurrencia , Cervicitis UterinaRESUMEN
Mucocele of the appendix is uncomrnon and rarely diagnosed preoperatively. The malignant rountpart-i.e. mucinous cystadenocarcinoma--has the same grross appearance and many micro scopic features in cornmon wilhe the benign form. It rnay be associated with ovarian mucinous cystadenoma of strikingly similar microscopic appearence. A serious complication is a rupture of the mucoeele resulting in pseudomyxoma peritonei. Each case of benign and malignant mucocelr of the appendix falsely diagnosecl as an oovarian tumor before laparotxumy are presented wilh a brief rieview of the literatures.