Processing of VEGF-C and -D by the Proprotein Convertases: Importance in Angiogenesis, Lymphangiogenesis, and Tumorigenesis, Geraldine Siegfried, Majid Khatib
Описание: Proprotein convertases (PCs) are a family of proteases including PC1, PC2, Furin, PC4, PACE4, PC5, and PC7. This title discusses a number of previous and recent findings on the PCs features, their implication in the regulation of multiple cellular functions that impact on the invasive/metastatic potential of cancer cells, and their clinical relevance in cancer patients.
Автор: Michael B. Kastan Название: Genetic Instability and Tumorigenesis ISBN: 3642644341 ISBN-13(EAN): 9783642644344 Издательство: Springer Рейтинг: Цена: 18167.00 р. Наличие на складе: Есть у поставщика Поставка под заказ.
Описание: KASTAN Cancer is a disease resulting from alterations of cellular genes which cause phe- notypic changes in somatic cells. The vast majority of genes which are altered in the cancer cells are not transmitted through the germ line, but rather become abnormal in somatic cells sometime during the lifetime of the individual.
Автор: David Heber; David Kritchevsky Название: Dietary Fats, Lipids, Hormones, and Tumorigenesis ISBN: 1461284503 ISBN-13(EAN): 9781461284505 Издательство: Springer Рейтинг: Цена: 27951.00 р. Наличие на складе: Есть у поставщика Поставка под заказ.
Описание: Based on the proceedings of the Nutrition and Cancer Prevention Scientific Symposium of the UCLA/NCI Clinical Nutrition Unit held in Los Angeles, California, November 14, 1994.
Описание: Many proprotein convertases (PC), especially furin and PACE4, are involved in pathological processes such as viral infection, inflammation, hypercholesterolemia, and cancer, and have been postulated as therapeutic targets for some of these diseases. In this chapter, we review mostly our work using animal models of squamous cancers that have been induced by chemical or UV carcinogenesis protocols to highlight the role of PCs in the development and progression of experimental tumors. After demonstrating in wild type mice the role of PACE4 in tumor progression as well as detecting the expression of PACE4 and furin in human non-melanoma skin cancers, we developed transgenic mice that over-express either PACE4 or furin in squamous epithelia, including the epidermis. This was accomplished by targeting the expression of the corresponding PC by using the promoter of the bovine keratin 5. Both K5-PACE4 and K5-Furin transgenic mice showed increased susceptibility to a two-stage carcinogenesis protocol of chemical carcinogenesis. Similar studies conducted in K5-PACE4 mice also showed an increased sensitivity to ultraviolet B radiation carcinogenesis. In most of these experiments, we were able to demonstrate that compared to the control wild type mice, the over-expression of the transgene in the epidermis increased the number of benign and malignant skin tumors and also had an effect on tumor progression as evidenced by the presence of less differentiated tumors and more frequent local and distant metastases in many of the transgenic lines. Interestingly, double transgenic mice in which PACE4 and furin are targeted to the epidermis did not show any additive effect, pointing to a probable in vivo overlap of functions at least in cutaneous tissues.The tumor-enhancing effects of PACE4 and furin further support their possible role as therapeutic targets. Furthermore, a proof of principle for PC inhibition as a therapeutic tool has been substantiated by an in vivo experiment in which the PC-inhibitor, decanoyl-RVKRchloromethylketone, was topically administrated to the skin of wild type and transgenic mice treated with chemical carcinogenesis protocols, resulting in a significant decrease of tumor development and progression.
Описание: Provides an overall review of all non-peptide PCSK inhibitors so far reported in the literature along with those identified recently for the first time and not yet published. The potential implications of these molecules as biochemical, therapeutical, or clinical agents is also discussed.
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