Association between RAD51 135 G/C polymorphism and risk of 3 common gynecological cancers: A meta-analysis.

AIM: Available data concerning the association between RAD51 135G/C (rs1801320) polymorphism and the risk of 3 common gynecological cancers still could not reach a consensus. Thus, we conducted a meta-analysis to explore the relationship. METHODS: Several electronic databases and bibliographies of relevant articles were screened to identify the studies up to July 2017. Then a meta-analysis was performed to evaluate the connection between 3 common gynecological tumors' susceptibility and RAD51 135G/C polymorphism in different inheritance models. Simultaneously, we did subgroup analysis and sensitivity analysis if necessary. RESULTS: A total of 11 articles including 14 studies involving 4097 cases and 5890 controls were included in this meta-analysis. Overall, RAD51 135G/C polymorphism increased the risk of 3 common gynecological tumors. The subgroup analysis stratified by cancer types- endometrial carcinoma (EC) and ovarian cancer (OC)-showed that RAD51 135G/C polymorphism increased the risk of EC: allele model (C vs G: odds ratio [OR] = 4.32, 95% confidence interval [CI] = 2.63-7.10, P < .00001), dominant model (CC + GC vs GG: OR = 2.28, 95% CI = 1.44-3.60, P = .004), recessive model (CC vs GC + GG: OR = 10.27, 95% CI = 14.71-22.38, P < .00001), and homozygous model (CC vs GG: OR = 7.26, 95% CI = 3.59-14.68, P < .00001), but there was no significant association between RAD51 135G/C polymorphism and OC. In the subgroup analysis stratified by source of controls, a significantly increased risk was observed in hospital-based studies. Nevertheless, the data showed RAD51 135G/C polymorphism had no link in population-based studies. CONCLUSIONS: This meta-analysis suggested that RAD51 135G/C polymorphism was a risk factor for the three common gynecological tumors, especially for EC among hospital-based populations.

Short hairpin RNA targeting Twist1 suppresses cell proliferation and improves chemosensitivity to cisplatin in HeLa human cervical cancer cells.

Development of multidrug resistance (MDR) remains a major hurdle to successful cancer chemotherapy and MDR1/P-gp overexpression is believed to be mainly responsible for MDR of tumor cells. Twist1, which is a highly conserved transcription factor that belongs to the family of basic helix-loop-helix proteins, has been shown to be a major regulator of the epithelial-mesenchymal transition (EMT), and therefore promotes carcinoma metastasis. Recently, a novel function of Twist1 was reported to confer radioresistance or chemoresistance in cervical cancer. However, mechanisms of such efficacy are not completely elucidated. In the present study, we firstly analyzed the relationship between Twist1 and MDR1/P-gp expression in human cervical cancer specimens and demonstrated a positive correlation between Twist1 and MDR1/P-gp expression in the same patient. Additionally, we provide the first evidence that silencing of Twist1 by RNAi downregulated MDR1/P-gp expression in HeLa cervical cancer cells, suppressed the cell proliferation, inhibited Rhodamine123 efflux activity of cells and sensitized cells to cisplatin treatment. Collectively, these findings suggest that Twist1-mediated modulation of MDR1/P-gp expression plays an important role in sensitization of cervical cancer cells to cisplatin, and also indicate a novel therapeutic strategy to overcome drug resistance through inactivation of Twist1 expression in cervical cancer.

Combination chemotherapy with 5-fluorouracil, methotrexate and etoposide for patients with high-risk gestational trophoblastic tumors: a report based on our 11-year clinical experiences.

OBJECTIVES: To evaluate the efficacy, toxicity, and survival of patients with high-risk gestational trophoblastic tumors (GTTs) treated with the 5-fluorouracil (5-FU), methotrexate (MTX) and etoposide (VP-16) regimen. METHODS: Between 1992 and 2003, 26 consecutive patients with FIGO-defined high-risk GTTs were treated with 5-FU, MTX and VP-16 regimen. Among them, 9 patients had received prior chemotherapy. Remission rate, causes of treatment failure, and toxicity were analyzed retrospectively. RESULTS: After treatment with 5-FU, MTX and VP-16 regimen, 21 of 26 gained complete respond (80.8%). Two patients were performed adjuvant hysterectomy and both cured ultimately. Five developed resistance (19.2%), and 1 died of widespread metastases (3.8%). All 5 patients who developed resistance were treated with multidrug regimen of etoposide, methotrexate, and actionmycin D alternating with cyclophosphamide and vincristine (the EMA/CO); 4 were salvaged and 1 died of refractory disease. No ones relapsed. WHO grade 4 leukocytopenia and thrombocytopenia with the 5-FU, MTX and VP-16 regimen occurred in 9.0% and 2.4%, respectively, of the total 167 cycles; other toxic effects were acceptable and manageable. With mean follow up of 37 months, neither relapse nor secondary tumor was observed. CONCLUSIONS: According to our 11 years of clinical observation, 5-FU, MTX and VP-16 chemotherapy is one of effective multiagent regimen for patients with high-risk GTTs. Its toxicity is mild and manageable. For patients with high-risk and refractory GTTs, this new triple salvage chemotherapy regimen may be an effective alternative.