Tumour progression

ET-1 also stimulates anti-apoptotic signal cascades in fibroblasts, vascular smooth muscles and endothelial cells (via phosphatidylinositol-3-kinase and Akt/pro-tein kinase B). In prostate and ovarian cancer, upregulation of endothelin synthesis and ETA receptors has been associated with a progression of the disease. The inhibiton of ETA receptors results in a reduced tumour growth. In malignant melanoma, ETB receptors are associated with tumour progression. Endothelins can also stimulate apoptosis in stretch-activated vessels via the ETB receptor, which contrasts the above-mentioned effects. The molecular basis for these differential anti- and pro-apoptotic reactions mediated by endothelins remains elusive. 

The semaphorin-plexin system has been shown to be involved both in tumour suppression and tumour progression. The genes encoding Sema3B and Sema3F... 

L. Single, N. J. Brown, and C. E. Lewis, The role of tumour-associated macrophages in tumour progression implications for new anticancer therapies, J.Pathol. 196(3), 254-265 (2002). 

Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T (2005). Opinion migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat Rev CancerS 744-749. 

The importance of NF-kB to inflammation, apoptosis resistance and tumour progression has resulted in the development of unique NF-kB inhibitors as part of cancer therapeutic regimens for GI and other cancers. Efforts are also being made to understand the efficacy of using natural substances obtained from plants, such as feverfew (e.g. parthenolide), bee glue (e.g. caffeic acid phenylethyl ester), tea (e.g. EGCG), spices (e.g. curcumin from turmeric) and mulberry figs (e.g. morin, a flavone) for the prevention both of persistent NF-kB activation and of the development of inflammatory pre-neoplastic lesions. 

Auge F, Hornebeck W, Laronze J-Y. A novel strategy for designing specific gelatmase A inhibitors potential use to control tumour progression. Crit Rev Oncol/Hematol 2004 49 277-82. 

Pollard JW. 2004. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 4 71-78. 

Helfman DM, Kim EJ, Lukanidin E, Grigorian M. 2005. The metastasis associated protein S100A4 role in tumour progression and metastasis. Br J Cancer 92(11) 1955—1958. 

TRPV6 overexpression also increases the rate of Ca2+-dependent cell proliferation which is a prerequisite for its potential role in tumour progression (Schwarz, et al., 2006). 

Cat B is an abundant and ubiquitously expressed cysteine peptidase of the papain family and makes up a major fraction of lysosomal enzymes that is capable of degrading components of the extracellular matrix in various diseases [30-32]. Cat B is also a prognostic marker for several types of cancer [33], and increased expression and secretion of cat B has been shown to be involved in the migration and invasion of various tumours [34—36], The precise role of cat B in solid tumours is not fully understood, but it has been proposed to participate, along with other cysteine cathepsins, in metastasis, angiogenesis, and tumour progression [37], Indeed, cat B inhibitors reduce both tumour cell motility and invasiveness in vitro [38], Recently, metal complexes based on rhenium, gold and palladium were shown to be effective inhibitors of cat B [39-44],... 

Henning W and Sturzbecher HW (2003) Homologous recombination and cell cycle checkpoints Rad51 in tumour progression and therapy resistance. Toxicology 193 91-109. 

Matsushita K, Takenouchi T, Kobayashi S, et al. HLA-DR antigen expression in colorectal carcinomas influence of expression by IFN-y in situ and its association with tumour progression. Br ) Cancer 1996 73 644-8. 

Brown, K., A. Buchmann and A. Balmain. Carcinogen-induced mutations in the mouse c-Ha-ras gene provide evidence of multiple pathways for tumour progression. Proc. Natl. Acad. Sci. USA 87 538-542, 1990. 

Studies on the molecular biology of tumour progression have emphasized the importance of the interaction between the tumour and host homeostatic... 

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