Dissemination Of Malignant Diseases Research Articles

Twist promotes angiogenesis in pancreatic cancer by targeting miR-497/VEGFA axis.

Angiogenesis is a critical step in the growth and dissemination of malignant diseases, including pancreatic cancer. Twist has been shown to stimulate angiogenesis in the tumor site. However, whether Twist contributes to angiogenesis in pancreatic cancer remains unknown. In this paper, we found that the expression of Twist was significantly increased in human pancreatic cancer cell lines and pancreatic cancer specimens. It is also closely engaged to adverse clinical feature, diminished survival and angiogenesis in pancreatic cancer patients. The up-regulation of Twist was found to be promoting cell growth, invasion and tubule formation of human umbilical vein endothelial cells (HUVECs) in vitro. By contrast, the silencing of Twist inhibited orthotopic xenograft tumor growth, metastasis and angiogenesis. Subsequent investigations disclosed that Twist was regulated by miR-497 directly, leading to the increased level of Vascular Endothelial Growth Factor-A (VEGFA). Moreover, gain-of-function and loss-of-function studies demonstrated that miR-497 could suppress the pro-proliferative, angiogenic and metastatic ability of pancreatic cancer cells. The ectopic expression of VEGFA obviously abrogated the anti-angiogenic effect induced by Twist knockdown, whereas the silencing of VEGFA markedly rescued the pro-angiogenic effect of Twist. By analyzing the expression levels of miR-497, Twist was found inversely correlated with miR-497 in pancreatic cancer tissues, and a positive correlation was found between Twist and VEGFA levels in pancreatic cancer specimens. In conclusion, our results suggested that the Twist/miR-497/VEGFA axis is significantly correlated with metastasis and angiogenesis in pancreatic cancer.

MiR-497 suppresses angiogenesis in breast carcinoma by targeting HIF-1α.

Angiogenesis is a key factor in the growth and dissemination of malignant diseases, including breast cancer, with significant implications for its clinical management. It is known that microRNAs (miRNAs) play important roles in regulating tumor properties in cancers. However, whether miR-497 contributes to breast cancer angiogenesis remains unknown. Our study demonstrated that miR-497 was significantly downregulated in breast cancer tissue samples and cell lines. Conditioned medium obtained from breast cancer cell line MCF-7, treated with miR-497 mimics, suppressed the proliferation and tube formation of human umbilical vein endothelial cells in vitro, in comparison with the untransfected cells or cells transfected with the control vector alone. Furthermore, western blot assay confirmed that the overexpression of miR-497 reduced VEGF and HIF-1α protein levels. In addition, stable transfection of miR-497 inhibited tumorigenicity and angiogenesis in vivo. Moreover, HIF-1α was also increased in the breast cancer cells under a hypoxic condition, while the ectopic expression of miR-497 partially restored its level. Taken together, our findings indicate that miR-497 is a potential target for the biological therapy of breast cancer. Moreover, miR-497 inhibited the growth of tumors and reduced angiogenesis in a nude mouse xenograft tumor model, which was probably caused by the downregulation of pro-angiogenic molecules, such as VEGF and HIF-1α.

MiR-497 inhibits epithelial mesenchymal transition in breast carcinoma by targeting Slug.

Epithelial to mesenchymal transition (EMT) is a critical step in the growth and dissemination of malignant diseases, including breast cancer. It is known that microRNAs (miRNAs) play important roles in the regulation of tumor properties in cancers. However, whether miR-497 contributes to EMT in breast cancer cells remains unknown. Our study demonstrated that the expression of miR-497 was significantly decreased in human breast cancer cell lines and breast cancer specimens. In breast cancer cells, EMT was inhibited and promoted by the over-expression as well as depletion of miR-497, respectively. Dual-Luciferase ReporterAassay confirmed that Slug was a direct target of miR-497. The upregulation of miR-497 in breast cancer cells suppressed cell proliferation and induced apoptosis both in vitro and in vivo. Correlation analysis indicated that miR-497 was highly negatively correlated with Slug expression in breast cancer specimens. The knockdown of Slug expression in breast cancer cells significantly suppressed cell proliferation and promoted apoptosis. Our results suggested that the expression of miR-497 is significantly correlated with EMT in breast cancer cells by regulating Slug at the transcriptional as well as translational levels. Therefore, targeting miR-497 may provide a novel strategy for the treatment of breast cancer.

Angiogenesis and hypoxic factors in colorectal cancer

Colorectal cancer is a common cause of cancer death in the developed world. Angiogenesis is a key factor in the growth and dissemination of malignant disease, including colorectal cancer, with significant implications for its clinical management. Over the past few years, significant inroads have been made into understanding the mechanisms and processes of angiogenesis in various malignancies. It is postulated that, with a greater understanding of the angiogenic mechanisms that govern tumor growth, anti-angiogenic compounds may be introduced to combine with conventional means to combat the growth and spread of malignant disease. This review discusses the mechanisms involved in tumor angiogenesis, highlighting its influence in colorectal cancer.

14. LIVER TRANSPLANTATION – CAMBRIDGE/KING'S SERIES

Between December 1983 and August 1986, 84 children were assessed for possible liver transplant. 18, mainly infants with biliary atresia, were not accepted because of features which made successful trasnplantation unlikely. 4 children were withdrawn from the programme by their parents. 9 died before a donor of suitable size or compatible blood group could be found. 9 await transplantation, 9 have been accepted for liver transplantation but are at present sufficiently well for this to be postponed. 35, aged 7mnths-16yrs, had liver grafts. Of these, 17 had biliary atresia, 5 fulminant or subacute hepatic failure, 3 malignant liver tumours and 2 metabolic disease. 15 died, 9 in the first 2 months mainly from primary graft failure or vascular thrombosis, later deaths being due to rejection, infection or dissemination of malignant disease. 2 died of disease in other organs with a normally functioning transplanted liver. 2 of the survivors have had a second liver transplant. 3 have significant hepatobiliary problems which may require retransplantation. The majority of survivors are engaged in normal activities for their age, growing and developing satisfactorily with normal biochemical tests of liver function & complete regression of cirrhosis. Their excellent quality of live is encouraging. Lack of donors, particularly for young infants & prevention of post-operative rejection & infection are continuing problems.