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TNF-Α (TUMOUR NECROSIS FACTOR- ALPHA) INHIBITORS AS NOVEL ANTITUMOR AGENTS. Kirandeep Kaur, Amritpal Kaur, Charanjeet Kaur, Dinesh Kumar, Harwinder Singh Rao

TNF-Α (TUMOUR NECROSIS FACTOR- ALPHA) INHIBITORS AS NOVEL ANTITUMOR AGENTS.

Kirandeep Kaur, Amritpal Kaur, Charanjeet Kaur, Dinesh Kumar, Harwinder Singh Rao

International Journal of Natural Product Science 2012: Spl Issue 1:192.

Abstract(RBIP-192)

Tumor necrosis factor-alpha (TNF-α), a cytokine has been implicated in the pathogenesis of cancer. It was found that TNF-α is responsible for cachexia associated with cancer and sepsis (cachectin). It has been known to be elevated in several malignancies. Present studies have shown that thalidomide inhibits TNF-α. TNF-α is mainly involved in neo-angiogenesis, and interacts with other proliferative cytokines such as interleukin-6 (IL-6), known to be involved in the pathogenesis of multiple myeloma. Angiogenesis involved in metastasis of cancers, is usually initiated with vasodilation mediated by nitric oxide (NO). Since TNF-α is a mediator of nitric oxide synthesis, so TNF-α inhibitors can be developed to inhibit tumor specific angiogenesis by inhibiting synthesis of nitric oxide which is mediator of angiogenesis. It has been found out that allyl isothiocyanate (AITC) and phenyl isothiocyanate (PITC) inhibited tumour-specific angiogenesis by downregulating TNF-α produced during angiogenesis. (+)-catechin is also known to inhibit tumour-specific angiogenesis by decreasing the production of TNF-α. Thalidomide and its analogs, lenalidomide and CC-4047 has shown potential efficacy in human trials for refractory multiple myeloma, cell lymphoma, glioma, metastatic melanoma and pancreatic cancer. Thalidomide is currently being considered for approval in newly diagnosed multiple myeloma by the FDA. TNF-α inhibitors can be better future antitumor candidates. Structures of some TNF-α inhibitors presently being investigated for their antitumor activity are given below:

Thalidomide Lenalidomide CC-4
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