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AIM: To investigate the mechanism of the involvement of SUMO-ylated Androgen receptor (AR) in tamoxifen resistance and the role of SUMO inhibitor ginkgolic acid in resistance. METHODS: Real-Time PCR was used to detect AR mRNA levels in parental cells MCF-7W and drug-resistant cells MCF-7R, AR protein levels and SUMO levels in MCF-7W and MCF-7R cells was performed by western blot, and CB/IP was applied to detect AR interacts with SUMOE3 ligase PIAS1 and HSP27 in MCF-7R cell chromatin, the transcriptional activity of SUMO AR was also evaluated by the fluorescent reporter gene experiment, the CCK-8 method and the trypan blue exclusion method were used to detect cell viability and cell viability respectively. RESULTS: The mRNA and protein expression levels of AR in MCF-7R cells were significantly higher than those in MCF-7W cells (P<0.05), and there was highly SUMOylated AR in MCF-7R cells. Further research found that there had an obvious interaction between AR and SUMO E3 ligase PIAS1 and HSP27, that was, the SUMOylated AR was modified by E3 ligase. Moreover, androgen R1881 could enhance the transcriptional activity of the SUMOylated AR in a concentration-dependent manner. Compared with ginkgo acid alone, 10 μmol/L of ginkgolic acid combined with 10 μmol/L of enzalutamide treated MCF-7R cells for 3 days, the cell number was significantly reduced, and the number of cell death increased significantly (P<0.05). CONCLUSION: The resistance mechanism of tamoxifen may be due to the enhanced AR transcription and activity increased by the hyperactive SUMOylated AR, SUMO inhibitor ginkgolic acid combined with AR antagonist enzalutamide can be a new strategy for the treatment of tamoxifen resistance.
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AIM: To construct and identify the mammary gland cell-specific conditional knockout of SENP7 by the Cre-loxP system. METHODS: The homozygous SENP7
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BACKGROUND:Hypertrophic differentiation of chondrocytes is the sign of starting endochondral ossification, and it is also an essential step in endochondral ossification, which is a cascade reaction and difficult to be blocked once started. The end result is the formation of bone structure. RNA interference is a post-transcriptional gene silencing. Relevant studies have shown that the use of RNA interference to block the expression of core binding factorα1 (Cbfα1) can effectively inhibit the formation of heterotopic ossification. OBJECTIVE:To use RNA intereference technology to suppress Cbfα1 expression so as to achieve the purpose of blocking the hypertrophic diferentiation of chondrocytes. METHODs: We constructed an adenovirus containing siRNA against Cbfα1 (Ad-Cbfα1-siRNA). Retinoic acid and interleukin-1α were used to induce hypertrophic differetiation of chondrocytes, and then Ad-Cbfα1-siRNA was utilized to inhibit the hypertrophic differentiation of chondrocytes. Immunohistochemistry method was used to analyze the expression of Cbfα1. RESULTS AND CONCLUSION:After induction with retinoic acid and interleukin-1α, the chondrocytes in the negative control virus group appeared to have hypertrophy and the expression of Cbfα1 was positive. In the Ad-Cbα1-siRNA group, the expression of Cbfα1 was negative. These findings suggest that the inhibition of Cbfα1 by RNA interference can be a powerful way to prevent the hypertrophic differentiation of chondrocytes .
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Objective To evaluate the short-and long-term outcomes of laparoscopy-assisted gastrectomy (LAG) for gastric cancer.Methods After studying the patients' demographic data,extent of gastrectomy and lymphadenectomy,as well as differentiation and tumor TNM stage,85 patients who underwent LAG were individually matched to 85 patients who underwent open surgery (OG) between October 2004 and March 2008.The operative time,intraoperative blood loss,postoperative recovery,complications,pathological findings,and follow-up data were compared between the two groups.Results The mean operative time was significantly longer in the LAG group than in the OG group (277 ± 62) min vs.(211 ±46) min,t =7.882,P ＜0.05,whereas intraoperative blood loss was significantly lower (161 ±90) ml vs.(267 ± 141) ml,t =-5.854,P ＜0.05.In addition,there was a significant reduction in the time to first flatus and postoperative hospital stay (3.7 ± 1.3) days vs.(4.2 ± 1.1) days and (10 ± 3) days vs.(12 ± 6) days,respectively t =-2.318,-2.325,P ＜ 0.05.There was no significant difference between the LAG group and OG group with regard to the number of harvested lymph nodes and overall postoperative complications.The 5-year disease-free survival rates and overall survival rates were 76％,78％,respectively,in LAG group and 75％,73％,respectively in OG group (all P ＞ 0.05).Conclusions LAG is suitable and minimally invasive for treating gastric cancer.Compared to OG,the LAG will not increase the risk of recurrence and mortality after surgery.