Alfordkilgore9781

9%) and 19 died of disease (19.2%). The overall survival rate was 75.8%. We found out that tumor size and high mitotic rate (>10 mitosis per hpf) were significant prognostic factors for survival. Presence of symptoms, ulceration, and tumor necrosis as well as tumor recurrence were also significant prognostic factors (p less then 0.01). CONCLUSIONS Esophageal GISTs' tumor size and mitotic rate are the most significant factors for survival. For dubious cases, a pre-operative biopsy can auspiciously establish the diagnosis of an esophageal GIST. Regarding surgical treatment, tumor enucleation can be safely and feasibly performed for relatively small, intact tumors, whereas large, aggressive tumors are resected with radical esophagectomy.PURPOSE Gliomas are aggressive brain tumors accounting for significant mortality across the globe. Biomarkers for early detection and therapeutic targets for efficient treatment are lacking for glioma. This study was undertaken to investigate the role and therapeutic implications of miR-22 in glioma. METHODS U-87 glioma cell line was used in this study. qRT-PCR was employed for expression analysis. MTT assay was used for determination of cell viability. Lipofectamine 2000 was used for transfection. Flow cytometry was used for cell analysis. Wound healing assay and transwell assay were used for monitoring cell migration and invasion. Western blot analysis was used for estimation of protein expression. RESULTS The miR-22 expression was found decreased in glioma cells. Overexpression of miR-22 resulted in arrest of the U-87 glioma cells at G2/M checkpoint of the cell cycle. The percentage of apoptotic U-87 cells in G2/M phase were 13.05% in negative control (NC) and 29.06% in miR-22 mimics transfected cells. The cell cycle arrest promoted by miR-22 overexpression was also associated with depletion of cyclin B1 expression in U-87 cells. Furthermore, miR-22 could also significantly increase the sensitivity of glioma U-87 cells to cisplatin. LY450139 ic50 The TargetScan analysis and dual luciferase assay showed SNAIL1 to be the target of miR-22. The expression of SNAIL1 was also enhanced in all the glioma cells and miR-22 overexpression could cause suppression of the SNAIL1 expression in U-87 cells. Furthermore, SNAIL1 silencing could also cause decline in the viability of the U-87 cells. The wound healing assay showed that miR-5 overexpression caused decrease in the migration of U-87 cells, while the transwell assay showed decline in the invasion of miR-22 mimics transfected U-87 cells. CONCLUSION Taken together, miR-22 may exhibit therapeutic implications in glioma and may prove useful in glioma treatment.PURPOSE Melanoma is one of the fatal human malignancies. Its incidence in humans is increasing constantly and therefore there is urgent need to develop effective therapies for its management. This study was therefore undertaken to investigate the anticancer effects of Daidzein on human melanoma cells and also an attempt was made to decipher the underlying mechanisms. METHODS MTT assay was used to determine the melanoma A-375 cells viability. Αcridine orange (AO)/ Εthidium bromide (EB) and Annexin V/propidium iodide (PI) assays were used to detect the cell apoptosis. Autophagy was detected by electron microscopy and cell cycle analysis was performed by flow cytometry. The protein expression was determined by western blot analysis. RESULTS The results of MTT assay showed that Daidzein causes significant decrease in the proliferation of the melanoma A-375 cells and showed an IC50 of 18 µM. However, the IC50 of Daidzein was very high against the normal HEMn-LP cells, indicative of low cytotoxicity. Flow cytometry showed significant arrest of the A-375 cells at the G0/G1 phase of the cell cycle. Western blot analysis showed that the molecule suppressed the expression cell cycle regulatory proteins such as cyclin D1, CDK4, CDK6 and p27. DAPI and annexin V/PI staining assays showed that Daidzein prompted apoptosis in A-375 melanoma cells which was concomitant with depletion of Bcl-2, increase of Bax and activation of cleavage of caspase-3 and caspase-9. Electron microscopic analysis showed that the molecule led to the development of autophagosomes in A-375 cells, which was also concomitant with increase in the expression of LC3B II and decrease in the expression of p62. Finally, Daidzein also suppressed the phosphorylation of PI3K and AKT, causing deactivation of the PI3K/AKT signalling pathway. CONCLUSION Daidzein may prove beneficial in the development of melanoma systemic therapy.PURPOSE Melanoma is one of the prevalent types of cancer and ranks 6th major cause of cancer associated mortality. In this study the anticancer effects of the carbazole alkaloid Heptazoline were investigated against a panel of melanoma cells. METHODS The normal BJ-5TA and melanoma cell lines MEL-CLS-1M MEL-CLS-2, MEL-CLS-3 were used in this study. MTT and colony formation assays were used to determine the proliferation rate of melanoma cells Aciridine orange (AO)/ ethidium bromide (EB) and annexin V/propidium iodide (PI) staining were used to check the apoptotic cell death. Cell cycle analysis was performed by flow cytometry and protein expression was checked by western blotting. RESULTS Heptazoline inhibited the growth of all the melanoma cell lines, exhibiting an IC50 of 15 to 40 µM against the melanoma cells. However, the normal skin cells had IC50 125 µM. The anticancer effects were found to be due to induction of apoptotic cell death which was associated with the upregulation of Bax, cleaved caspase 3, 9 and PARP and downregulation of Bcl-2. Furthermore, Heptazoline also triggered the G0/G1 arrest of melanoma cells. The effects of Heptazoline on the MAPK signalling pathway revealed that this molecule could inhibit the expression of p-p38 concentration-dependently. CONCLUSION Taken together, Heptazoline may prove a lead molecule in the development of systemic therapy of melanoma.PURPOSE Osteosarcoma is one of the rare but fatal malignancies. The high metastatic rate, late diagnosis, emergence of drug resistance against drugs such as doxorubicin, and the lack of therapeutic targets obstructs the treatment of osteosarcoma. This study was undertaken to investigate the role and therapeutic potential of miR-187 in human osteosarcoma cells. METHODS The WST-1 proliferation assay was used for investigation of cell viability. Transfections were carried out by Lipofectamine 2000 reagent. The qRT-PCR was used for expression analysis. DAPI, acridine orange (AO)/ethidium bromide (EB) and Annexin V/propidium iodide (PI) assay were used for apoptosis. Western blot analysis was used for the determination of protein expression. RESULTS The expression of miR-187 was significantly downregulated in human osteosarcoma cells. Out of all osteosarcoma cell lines the SAOS-2 showed the lowest expression of miR-187 and therefore this cell line was selected for further studies. Overexpression of miR-187 caused significant inhibition in the proliferation of SAOS-2 osteosarcoma cells.