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Because of the unsatisfactory treatment options for breast cancer (BC), there is a need to develop novel therapeutic approaches for this malignancy. One such strategy is chemotherapy using non-toxic dietary substances and botanical products. Studies have shown that Panduratin A (PA) possesses many health benefits, including anti-inflammatory, anti-bacterial, anti-oxidant and anti-cancer activities. In the present study, we provide evidence that PA treatment of MCF-7 BC cells resulted in a time- and dose-dependent inhibition of cell growth with an IC50 of 15 µM and no to little effect on normal human MCF-10A breast cells. To define the mechanism of these anti-proliferative effects of PA, we determined its effect critical molecular events known to regulate the cell cycle and apoptotic machinery. Immunofluorescence and flow cytometric analysis of Annexin V-FITC staining provided evidence for the induction of apoptosis. PA treatment of BC cells resulted in increased activity/expression of mitochondrial cytochrome C, caspases 7, 8 and 9 with a significant increase in the Bax:Bcl-2 ratio, suggesting the involvement of a mitochondrial-dependent apoptotic pathway. Furthermore, cell cycle analysis using flow cytometry showed that PA treatment of cells resulted in G0/G1 arrest in a dose-dependent manner. Immunoblot analysis data revealed that, in MCF-7 cell lines, PA treatment resulted in the dose-dependent (i) induction of p21WAF1/Cip1 and p27Kip1, (ii) downregulation of Cyclin dependent kinase (CDK) 4 and (iii) decrease in cyclin D1. These findings suggest that PA may be an effective therapeutic agent against BC.
Subject(s)
Humans , Apoptosis , Breast Neoplasms , Breast , Caspases , Cell Cycle Checkpoints , Cell Cycle , Cell Proliferation , Cyclin D1 , Cyclins , Cytochromes c , Down-Regulation , Drug Therapy , Flow Cytometry , Fluorescent Antibody Technique , Inhibitory Concentration 50 , Insurance Benefits , MCF-7 Cells , PhosphotransferasesABSTRACT
Objective To investigate the mutation characteristics and genotype of hepatitis B virus resistance gene in Nantong area,and provide scientific basis for clinical rational drug.Methods A total of 158 cases of chronic hepatitis B (CHB)pa-tients who were received with nucleos (T)ide analogues therapy for at least 2 years as the research object,and 30 cases of CHB patients who were not received nucleos (T)ide analogues for the treatment as the control group.PCR-sequencing method was used to detect the HBV P resistant gene and genotype,meanwhile,observe the relationship between three main mutation model and the levels of ALT and HBV DNA was also investigated.Results B genotype was detected in 42 (26.58%)out of 158 CHB patients,and 116 cases (73.42%)were C genotype.A total of 131 patients with different site mutations in P region,the mutation rate were 82.91%.There were totally 11 HBV mutation sites,including the main muta-tion site:M204I,L180M,M204V,A181V and A181T,the frequency of drug resistance were 41.14%,37.34%,22.15%, 11.39% and 10.13%,respectively.Moreover,11 mutation sites had 21 mutation patterns.In lamivudine (LAM)resistance associated mutations,the L180M and M204V sites were mainly co-occurrence,followed by M204I alone.In adefovir dipivoxil (ADV)resistance associated mutations,A181V was the main mutation site.Whereas,the drug resistance rate of entecavir (ETV)was low.Conclusion The main genotypes of HBV were type B and C in Nantong area,and C type was the dominant genotype.The resistance mutations mainly concentrated in LAM and ADV resistance associated mutations,while the resist-ance rate of ETV was low.Multi-locus drug-resistant mutation detection may help to detect viral resistance and guide clinical treatment better.
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<p><b>OBJECTIVE</b>To investigate the current status of smoking and passive smoking among Chinese females to provide evidence for related strategy development.</p><p><b>METHODS</b>Data from 32 720 women aged 45-65 years old who participated in the 2008 to 2010 Chinese Multi-center Women Breast Cancer Screening Project, were used to analyze the prevalence rates of smoking/heavy smoking, daily smoking, smoking cessation, successful smoking cessation, passive smoking, etc.</p><p><b>RESULTS</b>A total of 913 females, accounted for 2.8% of all the women in the study, had reported the history of smoking. There were significant differences seen regarding the prevalence rates of smoking in different regions (Beijing, 2.8%; Tianjin, 5.9%; Nanchang, 1.7%; Feicheng, 0.9%; Shenyang, 1.8%). The prevalence rates of current smoking, daily smoking, and heavy smoking were 1.8%, 1.0% and 0.2%, respectively. The prevalence rates of smoking and current smoking increased with age but not the prevalence rates of daily smoking and heavy smoking. Among the smokers, the median initiation age of smoking, the median daily cigarette per day, and median year of smoking were 30 years old, 10 cigarette, and 16 years, respectively. And the prevalence rates of smoking cessation and successful smoking cessation were 19.1% and 8.2%. The prevalence rate of passive smoking was 45.7% (12 730/27 874). After combing the number of smokers and the number of passive smokers, the total exposure rate to tobacco was 41.8% (13 670/32 720).</p><p><b>CONCLUSION</b>There was a relatively low level of smoking among Chinese females, so as the rate of smoking cessation. However, passive smoking presented a relatively high level among Chinese females.</p>
Subject(s)
Aged , Female , Humans , Middle Aged , China , Epidemiology , Prevalence , Smoking , Epidemiology , Tobacco Smoke PollutionABSTRACT
Background and purpose:MicroRNA-340 (miR-340) has been demonstrated to play a role of negative regulation in many kinds of tumor, however, there are few reports about the relationship between miR-340 in proliferation and apoptosis of breast cancer cell. This study was aimed to explore the effect of miR-340 on proliferation and apoptosis of breast cancer cell MDA-MB231. Methods: The pre-miR-340 or anti-miR-340 were transiently transfected into breast cancer cell MDA-MB231 with LipofectamineTM2000. miR-340 level was detected by RT-PCR. The Western blot was performed to detect the protein level of cleaved-caspase-3. The inhibition rate of cell proliferation was evaluated by MTT assay. The cell apoptosis was studied by lfow cytometry. Results:The pre-miR-340 facilitated the expression of miR-340 in MDA-MB231 cells. The pre-miR-340 enhanced the protein level of cleaved-caspase-3, inhibited the proliferation of MDA-MB231 cells and increased its apoptosis. On the contrary, the expression of miR-340 was inhibited by anti-miR-340 in MDA-MB231 cells. The protein level of cleaved-caspase-3 was reduced after the anti-miR-340-transfected MDA-MB231 cells. Anti-miR-340 promoted the proliferation of MDA-MB231 cells. Decreased apoptosis of MDA-MB231 cells was observed by lfow cytometry. Conclusion:The overexpression of miR-340 can effectively inhibit the proliferation and increase the apoptosis of MDA-MB231 cells, which may be explained by up-regulating of protein cleaved-caspase-3 level.
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Objective To evaluate the effect of neoadjuvant chemotherapy (NAC) by investigating the expression of cyclin D1 in human breast cancer before and after NAC.Methods Eighty-four cases of breast cancer were diagnosed by core biopsies.The expression level of cyclin D1 in cancer tissues was measured by immunohistochemical envision two-step method before and after NAC (pirarubicin and docetaxel regimen for 3-4 cycles).Results Complete remission (CR) occurred in 4 cases of 84 patients (4.76 ％) with 2 pathological complete response cases,partial response (PR) in 54 cases (64.29 ％),stability (SD) in 26 cases (30.95 ％) and no disease progression (PD) patients.The positive rate of cyclin D1 in cancer tissues [65.48 ％ (55/84)] was significantly decreased after NAC [39.29 ％ (33/84)] (x2 =11.55,P =0.001).In clinical level,the ease rate was significantly improved in patients whose cyclin D1 expression switched from positive [86.36 ％ (19/22)] to negative [45.45 ％ (15/33)] after NAC treatment (x2 =9.359,P =0.002).Conclusion NAC significantly decreases the expression of cyclin D1 in breast cancer tissues.Meanwhile,the ease rate is improved when cyclin D1 expression switched from positive to negative after NAC.Therefore,cyclin D1 expression can be used as an evaluation index for the efficiency of NAC.
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Objective To investigate the satisfaction of clinicians on clinical research associates (CRA)and its influencing factors,for the purpose of providing rationalized proposals on education of CRAs.Methods 141 clinicians were randomly sampled from tertiary hospital for questionnaire survey,using the 5-point Likert scale.The survey covers 4 levels,i.e.,the work attitude,professional knowledge and ability,communication skills,and project management capabilities,as well as 14 dimensions.Data processing and statistics were analyzed using SPSS 15.0 software.The attribute characteristics of the investigation subjects were analyzed using x2 of the contingency table,along with analysis of its correlation with the general satisfaction on CRAs.Results The mean values of the 12 indicators range 2.28 to 3.75,with low satisfaction in general.Among these indicators,satisfaction of the service attitude of the CRA,and of their familiarity with the pilot program and CRF completion axe the highest,respectively,74.04％and 61.70％.Satisfaction of the rest 10 indicators falls below 50.00％.The chisquare analysis showed no association between satisfaction and gender,education,job titles.The satisfaction is different(P＜0.05)between those trained and those not,while there exists a significant differences(P＜0.01)between those participating in different number of tests.Conclusion Clinicians have a low satisfaction on CRAs.It is recommended to strengthen the training,establish a CRA occupation certification system,and to strengthen the clinicians' emphasis and competency of clinical trials.These actions will normalize the industry of clinical trials and improve the level of clinical trials in China.
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ObjectiveTo investigate the clinicopathological characteristics of non-diabetic renal diseases (NDRD) in the patients with diabetes mellitus.MethodsClinicopatholigical data of 202 patients with diabetes mellitus and NDRD identified by renal biopsy from January 1st,2003 to December 31st,2010 were analyzed retrospectively.All the patients were divided into three groups:the young (≤35 years old),the middle-aged (36-59 years old) and the elder (≥60 years old).Clinicopathological characteristics were compared among 3 groups.ResultsIn the young group (n=33),42.4％ of patients presented as chronic glomerulonephritic syndrome,while 36.4％ as IgA nephropathy for pathology.In the middle-aged group(n=136),35.3％ of patients presented as chronic glomerulonephritic syndrome,27.2％ as nephritic syndrome,17.6％ as chronic renal failure,14.7％ as latent glomerulonephritis,and 5.1％ as acute renal failure,while42.6％ as IgA nephropathy for pathology.In the elder group(n=33),30.3％ of patients presented as nephritic syndrome,30.3％ as chronic renal failure,while 27.3％ as membranous nephropathy for pathology.ConclusionsIn clinical manifestation,young patients are mainly chronic glomerulonephritic syndrome,middle-aged patients are diversified,and elder patients are mainly nephritic syndrome andchronicrenalfailure. Inpathology, youngandmiddle-agedpatientsaremainlyIgA nephropathy,and elder patients are mainly membranous nephropathy.
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Objective To observe the role of short-term use of megestrol acetate in reducing the toxicity of chemotherapy in breast cancer and in improving the quality of life of patients, as well as its impact on neo-adjuvant chemotherapy effects. Methods The effection of adjuvant chemotherapy, toxicity, and the quality of life of 158 patients with breast cancer were investigated by a retrospective control study. The data were statistically analysized by X~2 test. Results There was no significant difference of neo-adjuvant chemotherapy effects between Megestrol acetate + CEF chemotherapy group and vitamin C + CEF chemotherapy group (Megestrol acetate + CEF chemotherapy group was 74. 84%, vitamin C + CEF chemotherapy group was 76.15) ; Megestrol acetate + CEF chemotherapy group had more modest bone marrow suppression and gas-trointestinal reactions and better food intake, weight, KPS score than vitamin C + CEF Chemotherapy group, all the differences being statistically significant (P < 0.05). Conclusion Short-term use of megestrol ace-tate can reduce the adverse effects derived from chemotherapy of breast cancer and improve the quality of life of patients with breast cancer and had no effects on the efficacy of the neo-adjuvant chemotherapy.
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Objective To investigate the changes of the cell cycle regulators ATM, Chk2 and p53 and cell cycle arrest in HeLa cells after cisplatin therapy. Methods The proliferation-inhibiting rates of HeLa cells induced by eisplatin of different concentrations were measured by MTT assays. The mRNA and protein expressions of ATM, Chk2 and p53 of HeLa cells with and withont cisplatin were detected by RT-PCR and Western blot, respectively. The cell cycle analysis was conducted by flow cytometric analysis. Results Cisplatin inhibited the proliferation of HeLa cells in a dose- and time-dependent manner. The mRNA and protein expressions of ATM, Chk2 and p53 were increased in HeLa cells treated with cisplatin. The cell cycle was arrested in G2/M phase in HeLa cells treated with cisplatin. Conclusion Activation of ATM, Chk2 and p53 might be critical in determining whether cells survive or undergo apoptesis. Targeting ATM, Chk2 and p53 pathway might he a promising strategy for reversing chemoresistance to clsplatin in cervical cancer.
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Objective To investigate the differential diagnosis value between breast phyllode tumor and breast fibroadenoma by comprehensive analysis of multiple parameters on color Doppler ultrasonography.Methods The manifestations or characteristics on color Doppler ultrasonography were analysed in 17 cases with breast phyllode tumor and 92 cases with breast fibroadenoma.Results Thinned skin was found in 3 cases of phyllode tumor of the breast(17.65%).Cystic areas were observed in 11 cases with phyllode tumor of the breast(64.71%).Varication inside the tumor was found in 12 cases with phyllode tumor of the breast(70.59%).Conclusions Thinned skin,cystic areas and varication inside the tumor are the important indicators in differential diagnosis for breast phyllode tumor from breast fibroadenoma,which may improve the accuracy of diagnosis for phyllode tumor of the breast.
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Cell immobilization is a new biotechnology The definition, classification, and carrier selection of cell immobilization are presented in details The technique is efficiently applied to treating strength organic wastewater, nutrient and heavy metals removal of wastewater, as well as hardly biodegradated wastewater It has a widely applied prospect in wastewater treatment