Chemotherapeutic drugs affect methylation of ER-α in breast cancer cells by down-regulating miR-148b / 中华内分泌外科杂志

Objective To investigate the effects of chemotherapeutic drugs on ER-α expression and methylation in breast cancer cells.Methods Human breast cancer cells MCF-7(ER+,Luminal A) were induced by paclitaxel(PTX) and epirubicin(EPI) for more than 6 months,with an incremental dose,respectively.The expression and methylation status of ER-α in MCF-7 cells were detected before and after drug treatment.miRNAs with consistent expression changes in MCF-7 cells after two drugs' treatment were screened by microarray,and verified by quantitative PCR (qPCR).Targets of the most significantly down-regulated miRNA were analyzed by bioinformatics.miRNA inhibitor was transfected into MCF-7 cells,miRNA mimic was transfected into MCF-7/PTX and MCF-7/EPI cells,then ER-α and DNA methyltransferase 1 (DNMT1) expression were detected by Western blot,and ER-α methylation was detected by quantitative methylation-specific PCR (qMSP).Results PTX resistant MCF-7/PTX cell line and EPI resistant MCF-7/EPI cell line were established.Both drug treatments caused a decrease in ER-α protein expression and an increase in methylation levels,with up-regulation of DNMT1 and his tone deacetylase 1 (HDAC 1) expression.miRNAs with consistent expression changes in MCF-7 cells after drug treatments were screened and verified by qPCR,the most significant down-regulation among which was miR-148b.Bioinformatics analysis,and further confirmed by luciferase reporter gene assay (Luciferas) that DNMT1 was a direct target of miR-148b.miR-148b inhibitor induced decreased expression of ER-α and increased methylation level in MCF-7 cells,accompanied by increased expression of DNMT1;whereas miR-148b mimic caused an increased expression of ER-α and decreased methylation level in MCF-7/PTX and MCF-7/EPI cells,with a decreased expression of DNMT1.Conclusion Chemotherapeutic drugs (represented by PTX and EPI) induce aberrant miRNA expression in breast cancer MCF-7 cells,and down-regulate miR-148b further to attenuate the inhibition of DNMT1 expression,which promote,hypermethylation and down-regulation of ER-α.

Comparison of the Clinical Effect of Different Surgical Methods Combined with Neoadjuvant Chemotherapy on Patients with Breast Cancer / 现代生物医学进展

Objective:To explore the clinical effect of different surgical methods combined with Neoadjuvant chemotherapy in treating patients with breast cancer.Methods:80 patients treated and diagnosed in our hospital from January,2012 to January,2014 were enrolled in the present study.According to the willingness,physical condition and financial situation,they were divided them into group A (23 cases) and group B (57 cases).Neoadjuvant chemotherapy of EC regimens (epirubicin+cyclophosphamide) was applied to both groups,on the basis of which,group A received breast-conserving surgery,group B received modified radical mastectomy.The clinical effect,breast cosmetic result,life quality,psychological states were compared in both groups.Results:The operation time,extubation time were significantly shorter than those of group B (p ＜0.05),the amount of bleeding,AMA,HRSD score,occurrence rate of complications in group A were significantly lower than those of group B (p＜0.05),the breast cosmetic result of group A was obviously better than that of group B (p＜0.05),and the QLQ-BR23 score in group A was significantly higher than that of group B (p＜0.05).The 2-year survival rate and 2 year recurrence rate showed no statistical difference between the two groups (p ＞0.05).Conclusion:Breast-conserving surgery combined with epirubicin neoadjuvant chemotherapy was effective in treating breast cancer,which could decrease the complications,improve the breast cosmetic result and quality of life.

Application of core needle biopsy guided by ultrasound in diagnosis of thyroid nodule / 中华内分泌外科杂志

Objective To explore the role of ultrasound-guided core needle biopsy in diagnosis and treatment of thyroid nodules.Methods 778 cases undergoing ultrasound-guided core needle biopsy in our department from Jan.2012 to Dec.2014 were retrospectively analyzed,and the sensitivity,specificity and accuracy were calculated.Results All the patients were operated successfully.Except for 21 nodules undiagnosed,16.4％ (124/757) were histologically diagnosed as malignant and 83.6％ (633/757) were benign.15 samples of the 124 malignant nodules were less than 10 millimeter in diameter.The sensitivity,specificity and accuracy were 100％,94.8％ and 95.6％,respectively.Of the ultrasound features,blood flow,boundary,internal situation and calcification were statistically significant between benign and malignant nodules,but not so between the groups of different greatest dimentions.Conclusion Ultrasound-guided core needle biopsy is safe and effective for obtaining thyroid nodule tissue,and it is helpful for diagnosis of thyroid diseases.

Methylation of ER and ER gene and its significance in primary and relapsed/metastatic lesions of breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the different expressions of ER and ER gene status between primary and relapsed/metastatic lesions and their clinical significance.</p><p><b>METHODS</b>ER and ER gene status of primary and relapse/metastatic breast cancer masked in 70 metastatic breast cancer patients were assessed by determination of methylation status by immunohistochemistry (IHC) and methylation specific polymerase chain reaction (MSP), respectively.</p><p><b>RESULTS</b>Positive rate of ER in the primary breast cancers was 64.3%, and in the relapse/metastatic lesions was 41.4% (P < 0.05). There were six patients whose positive ER status was changed to negative, among them the ER gene status was changed from demethylation to hypermethylation in four cases. Another four patients with negative ER status changed to positive, and their ER gene hypermethylation changed to ER demethylation status.</p><p><b>CONCLUSIONS</b>The discordance of ER expression status in primary and relapse/metastatic lesions of breast cancer might be related to DNA methylation status.</p>

Toxicity and telomerase activity of allicin combined with TFP chemotherapy for patients with advanced gastric carcinoma / 肿瘤研究与临床

ObjectiveObserve the efficacy, toxicity and the effection of telomerase activity of allicin combined with paclitaxel plus cisplatin and 5-Fu(TFP)chemotherapy for patients with advanced gastric carcinoma.MethodsFifty-four patients with advanced gastric carcinoma were randomly divided into two groups. A group was treated with allicin and TFP, B group was only treated with TFP. The chemotherapy was paclitaxel (135 mg/m2, dl, 8) plus cisplatin (75 mg/m2, d2-4) followed by 5-Fu (500 mg/m2 d1-5). Allicin was used in 60 days(3 times every day,once 20 mg).Telomerase activity was performed by enzyme-linked immunosorbent assay. ResultsThe total efficiency rate was 40.7 ％ (11/27) in A group and 33.3 ％ (9/27) in B group.There was no statistical difference between the two groups(~ = 0.079,P =0.779).There was significant difference in nausea and vomit (P =0.043), and the incidence of A group was 77.8 ％ (21/27) which was lower than that of B group[92.6 ％(25/27)].There was statistical difference in telomerase activity between the two groups(P =0.000).ConclusionAllicin could reduce the toxicity of chemotherapy and inhibit the telomerase activity in advanced gastric carcinoma.