Cancer stem cells (CSCs) play an important role in the development, invasion, and drug resistance of carcinoma, but the exact phenotype and characteristics of ovarian CSCs are still disputable. In this study, we identified cancer stem cell-like cells (CSC-LCs) and investigated their characteristics from the ovarian adenocarcinoma cell line 3AO. Our results showed that CSC-LCs were enriched in sphere-forming test and highly expressed CD44(+)CD24⁻. The spheres and CD24⁻ cells possessed strong tumorigenic ability by transplantation into nonobese diabetic/severe combined immunodeficient mice. CD44(+)CD24⁻ cells expressed stem cell markers and differentiated to CD44(+)CD24(+) cells by immunofluorescence assay and fluorescence-activated cell-sorting analysis. In vitro experiments verified that CD44(+)CD24⁻ cells were markedly resistant to carboplatin and paclitaxol. In conclusion, our study identifies the CD44(+)CD24⁻ phenotype, self-renewal, high tumorigenicity, differentiation potential, and drug resistance of ovarian CSC-LCs. Our findings may provide the evidence needed to explore a new strategy in the treatment of ovarian cancer.
Various evidences reveal that the human papillomavirus (HPV) is the single most important etiologic agent in cervical carcinoma (CC). To investigate the distribution of HPV genotypes in the patients with CC and its precursors in Zhejiang Province, China, a total of 631 eligible samples from patients in Zhejiang Province with CC (N ¼ 181), cervical intraepithelial neoplasia (CIN) II-III (N ¼ 345), and CIN I (N ¼ 105) were detected. Age-matched samples of 217 women without cervical neoplasia were detected as control. An improved polymerase chain reaction (PCR)-restriction fragment length polymorphism assay validated by Hybrid Capture II and PCR sequencing was designed for HPV genotype. The prevalence of HPV was 95.0% in CC, 88.4% in CIN II-III, and 73.3% in CIN I, while only 41.9% in control. High-risk/low-risk HPV ratio showed a significant trend of increase with increased grade of CIN and transformation to carcinoma. A total of 24 HPV genotypes were detected in CC and its precursors. Of those, HPV 16 (65.2%), 18 (9.4%), and 58 (9.4%) were the major HPV genotypes in CC, while HPV 16
This study was designed to analyze the outcomes of chemotherapy for high-risk gestational trophoblastic neoplasia (GTN) with EMA-CO regimen as primary and secondary protocol in China. Fifty-four patients with high-risk GTN received 292 EMA/CO treatment cycles between 1996 and 2005. Forty-five patients were primarily treated with EMA-CO, and nine were secondarily treated after failure to other combination chemotherapy. Adjuvant surgery and radiotherapy were used in the selected patients. Response, survival and related risk factors, as well as chemotherapy complications, were retrospectively analyzed. Thirty-five of forty-five patients (77.8%) receiving EMA-CO as first-line treatment achieved complete remission, and 77.8% (7/9) as secondary treatment. The overall survival rate was 87.0% in all high-risk GTN patients, with 93.3% (42/45) as primary therapy and 55.6% (5/9) as secondary therapy. The survival rates were significantly different between two groups (chi(2)= 6.434, P =0.011). Univariate analysis showed that the metastatic site and the number of metastatic organs were significant risk factors, but binomial distribution logistic regression analysis revealed that only the number of metastatic organs was an independent risk factor for the survival rate. No life-threatening toxicity and secondary malignancy were found. EMA-EP regimen was used for ten patients who were resistant to EMA-CO and three who relapsed after EMA-CO. Of those, 11 patients (84.6%) achieved complete remission. We conclude that EMA-CO regimen is an effective and safe primary therapy for high-risk GTN, but not an appropriate second-line protocol. The number of metastatic organs is an independent prognostic factor for the patient with high-risk GTN. EMA-EP regimen is a highly effective salvage therapy for those failing to EMA-CO.
Hairy and Enhancer-of-split homologues 1 and 5 (Hes1 and Hes5) are the basic helix-loop-helix transcriptional factors that negatively regulate the cell differentiation during embryogenesis. It has been reported that they may be involved in carcinogenesis in some tumors. The roles of Hes1 and Hes5 in development and progression of cervical carcinoma are not well documented todate. In the study, the expression of Hes1 and Hes5 were detected by immunohistochemistry in 295 cases with various degrees of cervical epithelial lesions, including 78 normal cervical epithelia, 31 mild dysplasia (CIN I), 77 moderate-severe dysplasia (CIN II-III), and 109 squamous cervical carcinomas (SCCs), and their association with various clinical pathologic prognostic variables were analyzed in 73 early-stage SCC patients who underwent surgery. Hes1 and Hes5 expression were found to be significantly higher in SCC compared with CIN as well as higher in CIN than normal cervical epithelia, and positively correlated with various prognostic factors in early-stage cervical carcinoma. Our findings suggest that Hes1 and Hes5 may be involved in carcinogenesis of the cervix and progression of cervical carcinoma. Hes1 and Hes5 overexpression are probably variables to predict poor prognosis of the patients with early-stage cervical carcinoma.
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