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@#The aim of this study was to investigate the effect of norcantharidin (NCTD) on the proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231.Western blot was used to detect the effect of NCTD on the expression levels of apoptosis-related proteins Bax/Bcl-2, cleaved-PARP/PARP/PARP, cleved-caspase-9, cleaved-caspase-3 and MCL-1 in MDA-MB-231 cells.Also, the expression levels of autophagy-related proteins LC3-II/LC3-I, Parkin and PINK1 in MDA-MB-231 cells were measured by Western blot.Flow cytometry was used to measure the effect of NCTD on the changes of mitochondrial membrane potential and mitochondrial reactive oxygen species (ROS).The effect of NCTD on autophagy flow in cells expressing mCherry-EGFP-LC3 was detected by a confocal microscope.Moreover, the effects of NCTD combined with chloroquine (CQ) or 3-methyladenine (3-MA) on the apoptosis of MDA-MB-231 cells were detected by flow cytometry.The results showed that NCTD significantly increased the expression levels of Bax/Bcl-2, cleaved-PARP/PARP, cleaved-caspase-9, cleasved-caspase-3 and LC3-II/LC3-I proteins, and promoted the mitochondrial translocation of Parkin, and blocked the autophagic flow in MDA-MB-231 cells. Moreover, NCTD combined with CQ accelerated apoptosis, while NCTD combined with 3-MA decreased apoptosis.These results suggest that NCTD can induce autophagy accumulation and lead to apoptosis of MDA-MB-231 cells.
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To assess the value of endorectal ultrasonography ( ERUS ) in predicting the pathological response to neoadjuvant chemoradiotherapy( NCRT ) for locally advanced rectal cancer( LARC) . Methods Ninety‐nine patients with LARC received NCRT and total mesorectal excision in our hospital were retrospectively analyzed . T he maximum length and thickness of rectal tumor were measured by ERUS both before NCRT ( ERUS1 ) and after NCRT following sugery ( ERUS2 ) ,and the length and thickness reduction rate were calculated . T he patients were classified into good responder group ( n ＝ 47 ) and poor responder group( n ＝ 52 ) ,or pathological complete response ( pCR) group ( n ＝ 25 ) and non‐pCR group ( n＝74) according to pathological tumor regression grade ( T RG ) . T he differences of various parameters were compared between groups . T he correlations between these parameters and T RG grading were analyzed by Spearman correlation analysis . T he ROC curve was used to evaluate the diagnostic efficacy of the parameter . Results T he length and thickness of ERUS2 were significantly shorter than that of ERUS1( all P ＜0 .05) . T he length and thickness of ERUS2 in good responder group were shorter than those in poor responder group ,while the length and thickness reduction rate were higher than those in poor responder group with significant difference ( all P ＜ 0 .05 ) . T he length and thickness of ERUS2 in pCR group were shorter than those in non‐pCR group ,w hile the length and thickness reduction rate were higher than those in non‐pCR group with significant difference ( all P ＜ 0 .05 ) . T he length and thickness of ERUS2 were positively correlated with T RG grading ( r ＝ 0 .577 ,0 .605 ; all P ＜ 0 .01 ) and the length and thickness reduction rate were negatively correlated with T RG grading ( r ＝ －0 .681 ,－0 .598 ; all P ＜0 .01 ) . ROC curve showed the cut‐off value of the length and thickness reduction rate to predict good responder were 41 .34% ,46 .46% , with corresponding AUC areas of 0 .843 ,0 .796 , sensitivity of 74 .5% ,70 .2% , and specificity of 76 .9% ,80 .8% ,respectively . ROC curve showed the cut‐off value of the length and thickness reduction rate to predict pCR were 57 .36% ,58 .52% ,with corresponding AUC areas of 0 .851 and 0 .895 , sensitivity of 68 .0% ,76 .0% ,and specificity of 94 .6% ,93 .2% ,respectively . Conclusions T he changes of length and thickness of tumor after NCRT are well correlated with treatment response . T he length and thickness reduction rate measured on ERUS present high accuracy in prediction of good response and pCR in LARC patients .
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Objective To investigate the value of endorectal ultrasonography (ERUS) inpreoperative assessment of rectal cancer post neoadjuvant chemoradiation therapy.Methods From Jan.2016 to Dec.2016,90 rectal cancer patients who underwent preoperative neoadjuvant chemoradiation therapy and total mesorectal excision surgery in the Sixth Affiliated Hospital of Sun Yat-Sen University were retrospectively analyzed,and all patients underwent ERUS examination post neoadjuvant chemoradiation therapy.Of these,64 patients were evaluated by ERUS pre and post neoadjuvant chemoradiation therapy and 26 patients were evaluated only post neoadjuvant chemoradiation therapy.Wilcoxon rank sum test for paired sample was performed to compare the distance from inferior margin of tumor to anal margin,the length and thickness of the tumor pre and post neoadjuvant chemoradiation therapy respectively in rectal cancer.Taken pathologic findings as golden standard,the accuracy of T staging assessed by ERUS post neoadjuvant chemoradiation therapy was evaluated.Results Compared with pre neoadjuvant chemoradiation therapy,the distance from inferior margin of tumor to anal margin significantly increased after neoadjuvant chemoradiation therapy [(58.63±21.71) mm vs (51.68± 19.81) mm],and the length [(26.10± 10.07) mm vs (40.82±9.18) mm] and thickness [(9.73±2.50) mm vs (14.92±5.30) mm] of tumor also evidently decreased post neoadjuvant chemoradiation therapy,respectively (Z were 4.996,6.153 and 6.076,all P ＜ 0.01).The final pathological T stage was pathologic complete response (pCR) or pT0 in 15 patients,pT1 in 3 patients,pT2 in 30 patients and pT3 in 42 patients.The diagnostic accuracy of T staging of rectal cancer post neoadjuvant chemoradiation therapy for ERUS was uT0 82.2％ (74/90),uT1 96.7％ (87/90),uT2 66.7％ (60/90),uT3 67.8％ (61/90) and uT4 96.7％ (87/90),and the overall accuracy was 82.2％ (74/90).Conclusion ERUS could effectively record the morphological changes of rectal cancer pre and post neoadjuvant chemoradiation therapy,which may contribute to the re-evaluation of the distance from inferior tumor margin to anal margin and the range and depth of tumor involvement pre surgical resection.
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Objective To evaluate the value of endorectal ultrasonography (ERUS) in assessment of mesorectal fascia (MRF) invasion in rectal cancer.Methods Data of 44 patients who accepted preoperative ERUS and total mesorectal excision surgery within a week were retrospective analyzed.There were 18 patients who accepted preoperative neoadjuvant chemotherapy and 26 patients didn't acceped.Taking the pathological diagnosis of circumferential resection margin (CRM) as the gold standard,the diagnostic efficiency of ERUS for the MRF invasion in rectal cancer was evaluated.Results The final pathological T staging was T1 in 2 cases,T2 in 17 cases and T3 in 25 cases.There were 2 cases of CRM positive results,and 42 cases of CRM negative results.With regard to the location of tumor,there were 16 cases located in low,and 28 cases in mid rectum.There were 26 cases located in anterior or antero-lateral wall of rectum,13 cases in posterior or postero-lateral wall,and 5 cases with a circle of rectum.The diagnostic accuracy were 83.33 ％ (15/18) and 92.31％ (24/26) for cases of accepting and not accepting the preoperative neoadjuvant chemotherapy;80.77％ (21/26) for cases located in anterior or antero-lateral wall,and 100％ (13/13) for cases located in posterior or postero-lateral wall;75.00％ (12/16)and 96.43 ％ (27/28) for low position and mid position tumors.The total diagnostic accuracy was 88.64％ (39/44).Conclusion ERUS can be an effective method in preoperative assessment of the MRF invasion in rectal cancer.
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Objective To investigate the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor on lipopolysaccharide (LPS)-induced changes in the mass and function of pancreatic β-cells.Methods RINm cells were cultured and treated with LPS alone or combined with different concentrations of sitagliptin for 24 h.The proliferation of RINm cells was detected by CCK-8 assay.Apoptotic rate was determined by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide flow cytometry.Insulin secretion was measured by enzyme-linked immunosorbent assay.The expression of IL-6 mRNA was displayed by RT-PCR.Results LPS significantly stimulated the proliferation of RINm cells (0.89 ± 0.04 vs 1.14 ± 0.08,P＜0.01),while LPS+sitagliptin showed no significant difference compared with LPS group.The cell apoptotic rate in LPS + 10-1 mmol/L sitagliptin group was significantly lower than that in LPS group.There were no significant differences in basal insulin secretion among all groups,but after the high/low glucose stimulation,LPS increased insulin secretion as compared with the control.The IL-6 mRNA expression in LPS+sitagliptin group was significantly lower than that in LPS group (0.77 ± 0.33 vs 1.30 ± 0.41,P =0.006).Conclusions DPP-4 inhibitor has no influence on LPS-induced proliferation of pancreatic β-cell,but it can inhibit LPS-induced apoptosis and insulin secretion,and IL-6 may be involved in the process.