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Jing Y.,Shaoxing University | Jing Y.,Soochow University of China | Guo S.,Nanjing Medical University | Zhang X.,Shaoxing University | And 4 more authors.
Molecular Medicine Reports | Year: 2014

The present study aimed to investigate the effects of small interfering (si)RNA interference of connexin 37 (Cx37) on subcutaneous gastric tumours in mice. Constructed lentiviruses carrying siRNA against Cx37 significantly knocked down Cx37 mRNA and protein expression in vitro. A total of 60 mice with gastric cancer were randomly divided into the Cx37 siRNA group, the mock-siRNA group and the control group. Cx37 siRNA, mock-siRNA and saline were separately injected (with the lentiviruses transfected into the gastric cancer cells). Following six weeks, the Cx37 mRNA expression, Cx37 protein expression and tumor apoptosis were detected using semiquantitative reverse transcription-polymerase chain reaction, western blot analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling, respectively. Six weeks following lentiviral transfection, the Cx37 mRNA levels in the Cx37 siRNA group, mock-siRNA group and saline group decreased to 42, 63 and 67%, respectively (P<0.05). The mock-siRNA group demonstrated no significant change in Cx37 levels compared with the control group. Western blot analysis revealed lower Cx37 protein levels in the Cx37-RNAi group than in the other groups (0.21±0.07 vs. 0.65±0.06 vs. 0.54±0.07), and that the apoptotic index of the Cx37-RNAi group was higher than those of the mock-siRNA and control groups (19.7±5.1 vs. 9.8±6.4 vs. 10.5±7.2%, 11.1±6.9; P<0.05). In conclusion, it was demonstrated that Cx37 siRNA is correlated with gastric cancer. Interference of Cx37 effectively reduces Cx37 mRNA and protein expression and promotes tumour apoptosis.


Fan Y.,Zhejiang Provincial Tumor Hospital
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2010

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) such as gefitinib and erlotinib are used as standard 2(nd)/3(rd) line therapy in previously treated advanced non-small cell lung cancer (NSCLC). However, the optimal treatment for patients who experienced disease progression after chemotherapy and EGFR-TKI is unclear. The aim of this study was to explore the efficacy and safety of a salvage chemotherapy in advanced NSCLC patients who failed the previous treatment of platinum-based chemotherapy and EGFR-TKI. Clinicopathological data of 55 cases of advanced NSCLC patients who failure of first-line platinum-based chemotherapy and subsequent treatment with TKI were collected and analyzed. The patients were of PS = 0-2, and with normal vital organ function. Patients received salvage chemotherapy until disease progression or unacceptable toxicity or the patient refused to continue receiving treatment. A chart review assessed the key outcomes including the objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS). Fifty-five patients were enrolled in this study from march 2007 to october 2009. The median age of patients was 55 years (range: 34 - 72), 60.0% were males, PS 0-1 patients were 65.5%, stage IV patients were 100%; 34.5% had a TKI treatment duration ≥ 6 months. Twenty-four patients received pemetrexed as salvage chemotherapy, 21 received docetaxal and 10 had other chemotherapy. All patients were evaluable for efficacy. Among them, 7 (12.7%) patients achieved PR, 21 (38.2%) patients SD, and 27 (49.1%) patients PD, with ORR of 12.7% and DCR of 50.9%. The median follow-up duration was 5.5 months, and the median PFS was 2.0 months. The ORR and PFS were not significantly related with gender, PS and chemotherapy regimens (all P > 0.05), but patients with EGFR-TKI treatment ≥ 6 months achieved a significantly better ORR and DCR than those < 6 months (ORR: 21.1% vs. 8.3%, P = 0.012; DCR: 73.3% vs. 38.9%, P = 0.017), mPFS was significant longer in the patients received ≥ 6 months of EGFR-TKI (4.5 vs. 2.0 months, P = 0.008). The toxicity was acceptable and there were no treatment-related deaths. Advanced NSCLC patients failed with the previous treatment of first-line platinum-based chemotherapy and EGFR-TKI may benefit from salvage chemotherapy, especially in patients who received ≥ 6 months of EGFR-TKI. The toxicity of the salvage chemotherapy is acceptable.

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