Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Epstein-Barr virus (EBV) is involved in the carcinogenesis of several human cancers such as nasopharyngeal carcinoma (NPC) and Burkitt lymphoma (BL). Given the consistent role of EBV in transformation and maintenance of malignant phenotype, antiviral strategies provide an attractive approach to target EBV-expressing cells. In that aim, we have tested the Cidofovir, which is an acyclic nucleoside phosphonate analog known to exert an antiproliferative activity in some human virus-related tumors. Here, we show that Cidofovir induces a downregulation of the EBV oncoprotein LMP1 associated with a decrease of the antiapoptotic Bcl-2 and an increase of the proapoptotic Bax protein in Raji (BL) and C15 (NPC) cells. Using BL cell line BL2 B95-8 (BL2 infected with the B95.8 strain of EBV), we addressed the relation between EBV genome expression and modulation of viral oncoproteins by Cidofovir and/or ionizing radiation (IR). Cidofovir was able to significantly reduce LMP1 and EBNA2 mRNA and protein expression. This effect was associated with inhibition of proliferation, stimulation of apoptosis, and decrease of Bcl-2 expression in BL2 B95.8 cells. In addition, Cidofovir enhanced the radiation-induced apoptosis and the radiosensitivity through the proteolytic cleavage of death effectors caspase-9 and -3, which was specifically induced by combined treatment in EBV-positive cells compared to their negative counterparts. Furthermore, the combined treatment in nude mice led to a complete tumor remission without increasing toxicity in two human EBV-related cancer xenografts (Raji and C15). These results provide the basis for a novel anticancer strategy to enhance the therapeutic ratio of IR in EBV-related cancers.
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PMID:Antiviral agent cidofovir decreases Epstein-Barr virus (EBV) oncoproteins and enhances the radiosensitivity in EBV-related malignancies. 1270 Jun 62

Recurrent respiratory papillomatosis (RRP) is characterized by benign wartlike growths in the larynx with occasional spread to the lungs. A broad range of therapeutic measures have been used to treat RRP; the primary treatment is laser vaporization of the lesions. Recurrences of the disease are common, and alternate methods of treatment are being used to prevent recurrence, including cidofovir. Cidofovir is a cytosine nucleotide analog with antiviral properties that is approved by the US Food and Drug Administration for treatment of cytomegalovirus retinitis and is currently being used off-label for RRP. Cidofovir has gained initial success in slowing the rate of disease recurrence when used at the time of surgery. However, the use of cidofovir lends concern to several adverse side effects, including the potential for carcinogenesis. We report here a 28-year-old woman who was treated with intralesional cidofovir at the time of surgery over the span of 27 months. The initial pathology results demonstrated benign disease with progression to severe dysplasia during the treatment time. Cidofovir's potential for carcinogenicity remains largely undefined, and thus, we are currently undertaking a project involving the evaluation of sequential paraffin-embedded samples of resections from a large cohort of patients with RRP treated at the University of Iowa Hospitals and Clinics.
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PMID:Case of progressive dysplasia concomitant with intralesional cidofovir administration for recurrent respiratory papillomatosis. 1635 2