Mechanism of Bicalutamide to Breast Cancer Cell Lines MDA-MB-453 and Inhibitory Effects of Its Combination with Everolimus / 肿瘤防治研究

Objective To investigate the effect of bicalutamide on migration and invasion of androgen receptor(AR) positive breast cancer cells and related mechanism, and the effect of mTOR inhibitor everolimus combined with bicalutamide on the proliferation of MDA-MB-453 cells. Methods Western blot was used to detect the expression change of mTOR, p-mTOR and p-S6 in breast cancer cell lines before and after bicalutamide treatment. Transwell assay was used to detect the cell viability. MTT assay was used to detect the proliferation of MDA-MB-453 cells treated by the combination of bicalutamide and everolimus. The combined effect of the two drugs was calculated by Jin Zhengjun's method. Results After six days of bicalutamide treatment, the expression of mTOR, p-mTOR and p-S6 were decreased in MDA-MB-453 cells (Ρ =0.034, 0.05, 0.03). The invasion and migration were inhibited in MDA-MB-453 cells (migration: t =4.88, P =0.001, invasion: t =2.684, P =0.028). The proliferation of MDA-MB-453 cells was inhibited after the treatment of bicalutamide combined with everolimus, and the Q value were all greater than 1.15. Conclusion Bicalutamide could inhibit the invasion and migration of MDA-MB-453, and the inhibition effect is affected by the expression level of AR. The combination of bicalutamide and everolimus could synergistically inhibit the proliferation of AR positive breast cancer cells.

Multiple gene mutation and prognostic factors in gastrointestinal stromal tumors / 中华普通外科杂志

Objective To investigate the status and significance of KIT,PDGFRA and DOG1 gene mutation in gastrointestinal stromal tumors (GIST).Methods 100 GIST patients treated in the First Affiliated Hospital of Guangxi Medical University between May 2002 and May 2013 were analyzed restrospectively.DNA was isolated and amplified for the all exons of KIT,PDGFRA and DOG1.Each PCR product was sequenced to find the position and type of mutation.Results KIT mutations were identified in 75 cases (75％).PDGFRA mutations were found in 16 cases (16％).No DOG1 mutations were found.The overall 5-year survival was 58.8％.Log-rank univariate survival analysis showed that the primary location,tumor size,metastasis,operational mode,type of tumor cells,invasion of the smrounding organs,invasion of the smooth muscle,mitotic counts of the tumor cells,deletions in exon 11 KIT and targeting therapy were significant prognostic factors (all P ＜ 0.05).COX regression model showed that tumor size,metastasis,operational method,invasion of the surrounding organs,mitotic counts of the tumor cehs,deletions in exon 11 KIT and targeting therapy were related to prognosis.Conclusion KIT and PDGFRA mutations are mutually exclusive.The overexpression mechanism of DOG1 is not related to DOG1 gene mutation.The related gene mutations affect the prognosis of GIST.

Treatment with portal vein-hepatic artery shunt for liver cirrhosis and portal hypertension in pigs / 中华肝胆外科杂志

Objective To observe the therapeutic effects of end-to-side and side-to-side portal vein-hepatic artery shunts (P-H shunt) in pigs with liver cirrhosis and portal hypertension.Methods There were 15 pigs in each group (control and experimental),and the P-H shunt was made in each animal to observe the process of blood flow into the liver and the reduction of portal vein blood pressure.Results The portal vein pressures before the P-H shunt of pigs in the control and experimental group were (20.51±0.74) cm H2O (1 cm H2O=0.098 kPa) and (30.82±2.53) cm H2O respectively (P＜0.05).Portal vein pressures 30 days after the P-H shunt were(19.75±0.84) cm H2O and (20.84± 1.36) cm H2 O respectively (P＞0.05).The portal vein pressure differences of pigs in the control and experimental group before P-H shunt were (7.20±0.34) cm H2O and (17.34±0.62) cm H2O respectively (P＜0.05).Pressures differences 30 days after the P-H shunt were (6.40±0.21) cm H2O and (7.84 ± 1.32) cm H2O respectively (P＜0.05).Splenic vein injection of methylene blue after the P-H shunt operation stained the liver well.No necrosis and hepatic encephalopathy occurred for 30 days after the P-H shunt,and the splenomegaly gradually returned to normal.Liver function was most affected after the operation and other biochemical markers were least affected.Conclusions The P-H shunt changed the channel of blood flow into the liver,the portal hemodynamic was not affected,and a new balanced mechanism was established to maintain the portal hemodynamic stability.However,further treatment was needed for liver function recovery.

An analysis on clinical features and prognostic factors of gastrointestinal stromal tumors / 中华普通外科杂志

Objective To study the prognostic factors of gastrointestinal stromal tumors (GIST).Methods A total of 144 GIST patients treated at the First Affiliated Hospital of Guangxi Medical University between January 1996 and December 2011 were analyzed restrospectively.Kaplan-Meier,log-rank test and Cox regression model were used.Results The overall 5-year survival was 59.6％.Log-rank univariate survival analysis showed that the primary location,tumor size,metastasis,operational method,type of tumor cells,invasion of the surrounding organs and tissues,invasion of the smooth muscle,cellularity of the tumor,mitotic counts of the tumor cells,Ki-67 labeling index,P53 expression and targeting therapy were significant prognostic factors (P ＜ 0.05).Cox regression model showed that tumor size,metastasis,operational method,surrounding organs and tissues invasion,cellularity of the tumor,mitotic counts of the tumor cells,P53 and targeting therapy were essential to improve the survival.Conclusions The study suggests that early diagnosis and comprehensive treatment consisting of operation and targeting therapy can significantly improve the survival of GIST.

Mutation screening of the BRCA1 gene in sporadic breast cancer in southern Chinese populations.

The comparison of freshly collected breast cancer tissue DNA with that of the matched blood specimens of 144 patients was studied, and breast tissue from 30 unrelated normal women without cancer was selected as controls. The entire BRCA1 coding sequence was amplified by PCR with primers especially designed for comprehensive mutation screening by single-strand conformation polymorphism (SSCP) analysis. Amplification and electrophoresis were repeated for the confirmation of altered migration patterns. Variant bands were subsequently cut from gels, resuspended in distilled water, subjected again to PCR, and then sequenced. The amplified fragments of exon 2 and exon 3, which were not suitable for SSCP (>300bp) were sequenced directly. A total of 20 nucleotide alterations were observed in the breast cancer tissue DNA, and all were single-base substitutions. Sixteen missense mutations (which change the coding from one amino acid to another) have been identified throughout the gene. Ten cases of single nucleotide changes in BRCA1 detected in the study without records in the BIC database consisted of two missense mutations in exon 5 (273C>G, 287A>T), one polymorphism in exon 11 (2630T>G), three missense mutations in exon 11 (2532T>G, 3191C>G, 3876C>A), one missense mutation in exon 12 (4285G>A), two missense mutations in exon 17 (5115T>C, 5116A>G), and one missense mutation in exon 18 (5206T>A). The same analysis was carried out on matched blood specimens for each of the 20 nucleotide alterations revealed to be present in the germline. No nucleotide alterations were detected in the controls. These results suggest that somatic mutations of BRCA1 are infrequent in sporadic breast cancer, and nucleotide alterations were more easily observed in the breast cancer tissue DNA. It is likely that there are other important susceptibility genes that remain to be identified in patients with sporadic breast cancer.

The evaluation of recurrent laryngeal nerves exposure during thyroid resection:a meta-analysis / 中国普通外科杂志

Objective To evaluate recurrent laryngeal nerves exposure during thyroid resection. Methods Nineteen case-control clinical trials were collected from relevant studies published in different Chinese databases, and 9269 cases were collected for analysis OR (odds ratios). 95% confidence intervals using the Mantel-Haenszel method for a fixed-effects model, and the Mantel-Haenszel method for a random-effects model were summarized. Both fixed effect model and random effect model were applied to analyze the results and heterogeneity. Results The injury rate of the recurrent laryngeal nerves was significantly lower in exposure group ( OR 0.29, 95% CI 0.16～0.54, P