It was previously reported that COX is expressed in most cancer tissues including those of the breast, and the presence of COX is associated with angiogenic vasculature in most tumors. Furthermore, celecoxib blocks angiogenesis and suppresses implanted human colon carcinoma cells in nude mice, and celecoxib has been shown to reduce microvessel density in human breast cancer. Thus, the present results can be viewed as providing support for the hypothesis of a link between apoptosis and inhibited cell proliferation, on the one hand, and angiogenesis on the other, through actions on COX and PGE.Bennett A, Charlier EM, McDonald AM, Simpson JS, Stamford IF and Zebro T: Prostaglandins and breast cancer.Bennett A, Berstock DA, Raja B and Stamford IF: Survival time after surgery is inversely related to the amounts of prostaglandins extracted from human breast cancers.Potter JD: Risk factors for colon neoplasia epidemiology and biology.Giovannucci E and Willett WC: Dietary factors and risk of colon cancer.Thun MJ, Namboodiri MM, Calle EE, Flanders WD and Heath CW Jr: Aspirin use and risk of fatal cancer.Hengartner MO: The biochemistry of apoptosis.Otsuki Y: Tissue specificity of apoptotic signal transduction.Greenb latt MS, Bennett WP, Holls te in M and Harr is CC: Mutations in the p tumor suppressor gene: clues to canceret io logy and mo lecu lar pa thogenes is. Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM, Edwards DA, Flickinger AG, Moore RJ and Seibert K: Antiangiogenic and antitumor activities of cyclooxygenase inhibitors.Chang SH, Liu CH, Conway R, Han DK, Nithipatikom K, Trifan OC, Lane TF and Hla T: Role of prostaglandin Edependent angiogenic switch in cyclooxygenase induced breast cancer progression.Carter CL, Allen C and Henson DE: Relation of tumor size, lymph node status, and survival in, breast cancer cases.Received July, Accepted October, Gefitinib is currently being applied in Dopamine hydrochloride clinical studies as either a monotherapy, or as part of a combination therapy against prostate, head and neck, gastric, breast, and colorectal tumors.However, success rates vary betweendifferent tumor types, and thus it is important to understand which molecular target are responsible for limiting the therapeutic efficacy of the drug.In this study, we ask whether expression of HER affects sensitivity to gefitinib in human lung cancer cells.We established two clones, LKHER and LKHER, by transfecting HER cDNA into LK, a NSCLC line with a low expression level of HER.These LKHER and LKHER were much more sensitive to the cytotoxic effects of gefitinib than the parental LK lines.LKHER transfectants showed constitutive formation of HERHER heterodimer, which were seen to associate with a regulatory subunit of phosphoinositidekinase, pA, when active.Treatment of LKHER cells with gefitinib markedly decreased the formation of HERHER heterodimers, HER basal phosphorylation, and the association of pA with HER.This study is the first to show that under basal growth conditions, HER sensitizes lowEGFR NSCLC cell lines to growth inhibition by gefitinib.Overexpression of EGFR is often associated with advanced tumor stages, metastasis, and poor clinical outcome of several human malignant tumors such as nonsmall cell lung cancer. During the last decade, the EGFR family has been targeted in order to develop novel anticancer drugs in the form of small molecules or monoclonal antibodies is an orally Imiquimod active, selective EGFR tyrosine kinase inhibitor that blocks the signal transduction pathway implicated in cancer growth.

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