ABSTRACT
Objective To investigate the effect of downregulated activating transcription factor 3 ( ATF3) expression on proliferation of adrenocortical carcinoma cells and its mechanisms. Methods Immunohistochemistry and Western blotting were used to detect the expression of ATF3 in human adrenocortical tumor tissues and cells. Adrenocortical carcinoma cells, Sw-13, and NCI-H259R cells, were transfected with siATF3 using lipidosome 2000, and expression of ATF3 mRNA was determined using RT-PCR; expression of ATF3, cleaved caspase 3, caspase 3, cleaved PARP, and PARP proteins were detected using Western blotting; cell growth inhibition rate and apoptosis rate were monitored using MTT and AnnexinV-FITC/PI, respectively. Sw-13 and NCI-H259R cells were treated with NVP-BEZ235, Perifosine, BKM120, IWP-2, PP2, KN93, Everolimus respectively followed by detected expression of ATF3 mRNA by realtime PCR. The effect of ATF3 on cell proliferation after inhibition of related signaling pathways were detected by MTT. Results The ATF3 in human adrenocortical gland tumor tissues and cells showed high expression. The levels of ATF3 mRNA and protein in Sw-13 and NCI-F259R cells transfected with siATF3 were significantly reduced. Compared with the negative control group ( NC siRNA), siATF3 transfection significantly inhibited the proliferation of Sw-13 and NCI-F259R cells ( P＜0. 05 ), and increased the apoptosis rate ( P＜0.05). Western blotting shown that the levels of cleaved caspase 3 and cleaved PARP protein in siATF3 transfected cells increased significantly; and realtime PCR results indicated that the expression of ATF3 mRNA was dramatically inhibited by PP2, KN93, and IWP-2 in NCI-F259R cells compared with control group ( DMSO ); but ATF3 significantly promoted the proliferation activity of NCI-F259R cells which treated by PP2, KN93, and IWP-2 signaling inhibitors. Conclusion High expression of ATF3 is existed in adrenocortical carcinoma cells. Downregulated ATF3 expression may inhibit cell proliferation and activate apoptosis pathway, resulting in apoptosis in Sw-13 and NCI-F259R cells, this mechanism of action is related to activating Wnt/β-catenin, CaMKI, and SRC pathway.
ABSTRACT
OBJECTIVE:To compare therapeutic efficacy and safety of lobaplatin or cisplatin combined with tegafur,gimeracil and oteracil potassium in the treatment of advanced metastatic breast cancer.METHODS:A total of 160 patients with advanced metastatic breast cancer were randomly divided into observation group and control group,with 80 cases in each group.Control group was given Cisplatin injection 30 mg/m2 intravenously,every 3 weeks Tegafur,Gimeracil and Oteracil Potassium capsules 50 mg orally after meal,twice a day,for consecutive 14 days.Observation group was given Lobaplatin for injection 30 mg/m2 intravenously,every 3 weeks+Tegafur,Gimeracil and Oteracil Potassium capsules (same usage and dosage as control group),every 3 weeks.A treatment course lasted for 3 weeks,and both groups received 2 courses.Short-term efficacies (ORR、DCR),chemotherapy effects of lymph node,lung,bone and liver,ADR and long-term efficacy were compared between 2 groups.RESULTS:After treatment,ORR(67.50％ vs.46.25％),DCR(85.00％ vs.66.25％),ORR of lymph node metastasis (71.43％ vs.47.83％),ORR of lung metastasis (60.71％ vs.40.00％),DCR of lung metastasis (78.57％ vs.56.00％),ORR of bone metastasis (28.57％ vs.16.67％),1-year survival rates (75.00％ vs.52.50％) and 2-years survival rates (42.50％ vs.17.50％) of observation group were significantly higher than control group;the incidence of chemotherapy ADR in observation group was significantly lower than control group (43.75％ vs.70.00％),with statistical significance (P＜0.05).There was no statistical significance in lymph node metastasis DCR,bone tissue metastasis DCR,liver metastasis ORR and DCR,or half year sarvival rate between 2 groups (P＞0.05).CONCLUSIONS:Compared to cisplatin combined with tegafur,gimeracil and oteracil potassium,lobaplatin combined with tegafur,gimeracil and oteracil potassium show better short-term therapeutic efficacy,therapeutic efficacy of lymph node metastasis,bone metastasis and lung metastasis,more than 1-year long-term therapeutic efficacy and safety in the treatment of advanced metastatic breast cancer.
ABSTRACT
Polycystic ovary syndrome [PCOS] is highly associated with non-alcoholic fatty liver disease [NAFLD]. There are extensive ethnic differences in the clinical manifestations, pathological changes, and ovarian changes in women with PCOS. To investigate the prevalence and clinical characteristics of NAFLD in Chinese women with PCOS. Non-pregnant women with PCOS [N= 602] and matched controls without PCOS [N=588] were recruited. Basal endocrine, oral glucose tolerance test, insulin release level, lipid level, blood pressure, and body mass index [BMI] were measured. Liver biochemical and B-hepatitis and C-hepatitis indices were determined. NAFLD was significantly more prevalent in women with PCOS than controls [32.9% vs.18.5%] and included 113 [57.1%] mild, 75 [37.8%] moderate and 10 [5.1%] severe cases. Luteinizing hormone was significantly lower in PCOS women with NAFLD than without NAFLD. In the PCOS group, NAFLD prevalence and severity increased with BMI. The liver index was significantly higher [p<0.001], and the quantitative insulin sensitivity check index and high density lipoprotein cholesterol were significantly lower [p<0.001] in the PCOS group than controls. Insulin resistance, abdominal obesity, diabetes mellitus, abnormal glucose tolerance, liver dysfunction, dyslipidemia, hypertension, and metabolic syndrome were significantly more prevalent in the NAFLD group than controls. Chinese women with PCOS have a high prevalence of mostly mild and moderate NAFLD, not significantly associated with hyperandrogenism that increased significantly with BMI. Insulin resistance and metabolic abnormalities are important factors associated with NAFLD. Chinese women with BMI >/= 24 kg/m[2] P2P should be screened for NAFLD