Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer: a randomized, non-inferiority, multicenter trial / 医学前沿

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.

Expression and prognosis significance of P16 in cervical cancer / 实用医学杂志

Objective To access the expression of germ P16 in cervical cancer patients , find out the connection between with the expression in germ of P16 and the prognosis of cervical cancer , and discuss whether P16 can role as an indicator to predict the prognosis. Methods The pathological sections of all 74 cases were tested for the presence of P16 germ , using an immunohistochemistry technique. And the results were analyzed to investigate the value of P16 on the prediction of prognosis of cervical cancer. Results Of all 74 cervical cancer cases, there are 63 cases show positive expression of P16, with the positive expression rate of 85% (63/74). The positive expression of gene P16 is associated with the prognosis of cervical cancer (P = 0.041). The cumulative survival rate for two years of the positive expression set is 85.2%, and the negative set 100%, which is statistically significant (P = 0.043). Positiveexpression of P16 is closely related (P 0.05) with TNM and histological differentiation. Conclusions We suggest that the expression of germ P16 is closely connected prognosis in cervical cancer , and it might be used as one of indicator to predict the prognosis of cervical cancer.

Silencing MTA1 by RNAi reverses adhesion, migration and invasiveness of cervical cancer cells (SiHa) via altered expression of p53, and E-cadherin/β-catenin complex / 华中科技大学学报（医学）（英德文版）

It has been reported that metastasis-associated gene 1 (Mta1) is overexpressed in many malignant tumors with high metastatic potential. In addition, some studies indicated that MTA1 participated in invasion, metastasis, and survival of cancer cells by regulating cell migration, adhesion and proliferation. But the role of MTA1 is unclear in vitro in the development of cervical cancer cells. This study investigated whether and how MTA1 mediated cell proliferation, migration, invasion and adhesion in cervical cancer. MTA1 expression level was detected by Western blot in two cervical cancer cell lines of different invasion potentials. The effects of MTA1 expression on SiHa cell apoptosis, cycle, proliferation, migration, invasion and adhesion were tested by flow cytometry, MTT, wound-healing assay, Transwell assay and adhesion assay, respectively. The expression levels of p53, E-cadherin, and β-catenin activity were evaluated in untreated and treated cells. The results showed that MTA1 protein expression was significantly higher in SiHa than in HeLa, which was correlated well with the potential of migration and invasion in both cell lines. Furthermore, the cell invasion, migration and adhesion capabilities were decreased after inhibition of MTA1 expression mediated by Mta1-siRNA transfection in SiHa. However, no significant differences were found in cell apoptosis, cycle, and proliferation. In addition, E-cadherin and p53 protein levels were significantly up-regulated, while β-catenin was significantly down-regulated in SiHa transfected with the siRNA. These results demonstrated that MTA1 played an important role in the migration and invasion of cervical cancer cells. It was speculated that the decreased migration and invasion capability by inhibiting the MTA1 expression in the SiHa cell line may be mediated through the altered expression of p53, and E-cadherin/β-catenin complex. MTA1 could serve as a potential therapeutic target in cervical cancer.

Proteasome inhibitors sensitize ovarian cancer cells to cisplatin / 中华妇产科杂志

Objective To explore the sensitivity and the molecular mechanism of cisplatinresistance ovarian cancer cell line C13 to proteasome inhibitors and the combination with cisplatin. Methods After different treatments, methyl thiazolyl tetrazolium (MTT) assay was applied to examine the cell viability, annexin-V/propidium iodide(PI) apoptosis detection kit was used to determine the apoptosis rate of different groups, western blot assay was introduced to evaluate the expression levels of Fas-associated death domain-like interleukin-1 beta converting enzyme inhibitory protein (cFLIPs), and the activity of caspase-8 was examined. Results MTT assay shown that the cell viability ratios of combination group at serial time points from 12, 24, 36, 48, 60, 72 hours were ( 56.0 ± 8.4 ) %, (44.7 ± 7.3 ) %, ( 33.7 ±11.2) %, (27.6 ± 8.0) %, (27. 6 ± 7.6) % and (28.1 ± 2.4) %, which were much lower than those of cisplatin group (P <0.05). After treated for 24 hours, apoptosis rates of cisplatin group, bortezomib group and combination group were ( 16.7 ± 1.7) %, (23.4 ± 2.1 ) % and (26.9 ± 1.6) %, respectively. The rate of combination group was much higher than that of non-treated group and that of cisplatin group or bortezomib group ( P < 0.05 ). Western blot assay showed the changes of expression levels of cFLIPs, which were downregulated seriously after cisplatin, bortezomib or combination treatment [ (43.2 ± 2.3 )% vs( 75.7 ± 3.0)%vs (67.9 ± 2.1 ) %, P < 0.05 ]. The caspase-8 activity of combination group was (5.6 ± 1.6) folds than that of non-treated group, which was higher than those of other two groups [ ( 2.3 ± 1.0) and (4.2 ± 0.9 ) folds,P < 0.05 ]. Conclusions The tumor cell lethal effect of cisplatin could be increase significantly by the combination application of proteasome inhibitors, bortezomib. And the cFLIPs/caspase-8 signaling pathway may be play an important role in the molecular mechanism of the combination treatment.

Proteasome inhibitors sensitize ovarian cancer cells to paclitaxel induced apoptosis / 中华妇产科杂志

Objective To explore the semitivity of ovarian cancer cell line SKOV3 to paclitaxel,oroteasome inhibitors,bortezomib,and their combination.Methods The methyl thiazolyl tetrazolitim (MTT)assay was applied to examine the cell viability after treatment.The annexin V-propidium iodide apoptosis detection kit was used to determine the apoptosis rate of different groups.Western blot assay was used to evaluate the expression levels of phosphorylated protein kinase B(AKT)and glycogen synthase kinase-3 beta(GSK-3β).Results In MTT assay,the cell viability ratios of the combination group at serial time points from 12,24,36,48 and 72 hours Were(65.2±5.8)%,(58.3±14.4)%,(35.3±5.0)%,(19.2±1.5)%,and(11.4 ±2.5)%,which were significantly lower than those of the paclitaxel group (P<0.05).After arug treatments,apoptosis rates of paclitaxel group,bortezomib group and the combination group were (14.7±0.5)%,(15.1±0.8)%and(20.5±0.7)%respectively.The rate of the combination group was significantly higher than that of non-treated group and paclitaxel group(P<0.05).Western blot assay showed the changes in expression levels of phosphorylated AKT and GSK-3β,which were decreased significantly after paclitaxd and bortezomib combination treatment [(3.2±0.8)%,(19.3±0.4)%;P<0.05].Conclusions The lethal effect of paclitaxel on tumor cells could be increased significantly by its combination with proteasome inhibitors,bertezomib.The AKT/GSK-3β signaling pathway plays an important role in the molecular mechanism of the combination treatment.