Bazedoxifene (BZA) is a third-generation selective estrogen receptor modulator (SERM) that has been approved for the prevention and treatment of postmenopausal osteoporosis. It has antitumor activity; however, its mechanism of action remains unclear. In the present study, we characterized the effects of BZA and several other SERMs on the proliferation of hormone-dependent MCF-7 and T47D breast cancer cells and hormone-independent MCF-7:5C and MCF-7:2A cells and examined its mechanism of action in these cells. We found that all of the SERMs inhibited the growth of MCF-7, T47D, and MCF-7:2A cells; however, only BZA and fulvestrant (FUL) inhibited the growth of hormone-independent MCF-7:5C cells. Cell cycle analysis revealed that BZA and FUL induced G 1 blockade in MCF-7:5C cells; however, BZA down-regulated cyclin D1, which was constitutively overexpressed in these cells, whereas FUL suppressed cyclin A. Further analysis revealed that small interfering RNA knockdown of cyclin D1 reduced the basal growth of MCF-7:5C cells, and it blocked the ability of BZA to induce G 1 arrest in these cells. BZA also down-regulated estrogen receptor-␣ (ER␣) protein by increasing its degradation and suppressing cyclin D1 promoter activity in MCF-7:5C cells. Finally, molecular modeling studies demonstrated that BZA bound to ER␣ in an orientation similar to raloxifene; however, a number of residues adopted different conformations in the induced-fit docking poses compared with the experimental structure of ER␣-raloxifene. Together, these findings indicate that BZA is distinct from other SERMs in its ability to inhibit hormone-independent breast cancer cell growth and to regulate ER␣ and cyclin D1 expression in resistant cells.
Background Gastric cancer is also a leading cancer in Bangladesh like that of the global incidences. It is speculated that environmental, bacterial infection and molecular factors might have been carrying the key role of rising trend of the disease. This study was aimed to investigate the association of mutated p53 gene with of Helicobacter pylori ( H. pylori ) infection, clinicopathological and some environmental factors of the gastric cancer patients. Methods This cross-sectional study was carried out from January 2015 to December 2016 in a specialized cancer hospital of Bangladesh. Patients were selected randomly who were admitted for surgical intervention after diagnosis as adenocarcinoma of the stomach and physically fit for surgery. After admission proper evaluation of the patients was done. Tissue sample from the gastrectomy specimen along with the blood sample was sent to the related laboratories. After DNA extraction for p53 , exons 5 and 6, they were adjusted for proper primer designing. Appropriate sequencing analysis of the result was done. Status of p53 was investigated to see their association with the result of the H. pylori , age and sex, tumor status, smoking and extra salt intake of the patients. Result of the study was calculated and analyzed by Chi-square and binomial logistic regression to find the association amongst them. Results Among the 71 patients, mean age was 52.96 years old, male: female ratio were 48:23, age group above 41 years were 53 (74.6%), proliferative and ulceroproliferative group of the tumor dominated (87.3%). There were 52 cases with (73.2%) p53 mutation. Among the 51 H. pylori positive cases, 41 (80%) had p53 mutation (P = 0.033). Tumor size and lymph node status were found to be associated with the gene mutation (P = 0.05). Age also had strong correlation with the mutation (P = 0.015). Gene mutation was found mostly among the younger (≤ 40 years) group of patients (94.4%). Patient with extra salt intake was also found related with the mutation (P = 0.03). Conclusions Environmental and genetic factors seem to be risk factors for gastric cancer in Bangladesh. Nationwide anti H. pylori drive and further molecular research could elicit the other risk factors which might help to reduce the gastric cancer incidences in the country after taking appropriate measures.
Gastric Cancer (GC) is one of the important malignancies which causes huge morbidity and mortality throughout the globe. This study was done to analyze the epidemiological and clinicopathological aspects of gastric cancer. It was a retrospective study conducted at National Institute of Cancer Research & Hospital, Dhaka from 1st January to 31st December 2013. In total, 114 histopathologically confirmed patients with GC were included in the study. Univariate methods (Mann-Whitney U-test, and Chisquare) were used for analysis. Among 114 cases, 81 (71.1%) were male. Sex ratio (Male: Female) was 2.45:1. The mean age of the patients was 52.9 years (SD ±12.6) at the time of the diagnosis. Weight loss, as a frequent symptom at the time of diagnosis, was observed in 85.1% of the cases. All of the patients were diagnosed with advanced pathologic stage and tumour grading was welldifferentiated 13.1%, moderate 51.8% and poorly differentiated 35.1%. In 72.8% of the patients, the tumours were located in the distal part of the stomach. All the patients were in the advanced stages of GC, which favours a poor survival. Male are more frequently affected female. lack of education, poor sanitation, high salt intake, low socioeconomic conditions are associated with increase chance of gastric cancer. Therefore, further comprehensive study of etiology and risk factors of GC, earlier detection in younger ages and in primary stages of tumour are needed. Weight loss, anorxia, abdominal pain and vomiting in elderly could be considered as alarm symptoms for GC diagnosis. JCMCTA 2016 ; 27 (1) : 51 - 54
Background: Venous thromboembolism remains a common cause of morbidity and sometimescause of death in surgical practice. In developed world about 10% of hospital deathsare due to pulmonary embolism resulting from deep vein thrombosis( DVT). DVT in Asiancountries is not a rare condition. Objective: The purpose of the study was to find the incidence ,demgraophic characterand risk factors of deep vein thrombosis. Methods: 150patients undergoing emergency or elective operation of more than one hourof duration was selected for study. Patients evaluated by history, clinical examination andduplex scan. Collected analyzed by computer program. Results: 102 cases were male and 48 cases were female. The incidence of DVT in malewas 36.3% while among females it was 27.5%. venous thrombosis in age group above 50yrs is quite high, (43.33%) . One-fifth of the DVT patients were smokers. Longer duration ofoperation procedure was correlated with development of DVT and development of DVT waslittle higher in emergency operation than elective one. The occurrence of the condition insome co-morbid states especially diabetes mellitus (36. 7%) and cancer (33.3%) is noteworthy.Out of 51 DVT patients more than 84% developed sub-clinical DVT. Conclusion: In Bangladesh it is assumed that DVT is rare. But the current study revealsthat the incidence of postoperative DVT in Bangladesh is not that much rare event. Journal of Surgical Sciences (2016) Vol. 20 (2) :42-45
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