Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA) is a potent and selective antiretroviral agent which is currently evaluated in its oral prodrug form, bis(POM)PMEA (adefovir dipivoxil), in phase II and III clinical trials in human hepatitis B virus (HBV)- and human immunodeficiency virus (HIV)-infected individuals, respectively. We have now found that PMEA is also a potent inhibitor of growth of the highly aggressive choriocarcinoma tumor arising from rat choriocarcinoma RCHO cells grafted under the kidney capsule of syngeneic WKA/H rats. In untreated rats, massive invasive RCHO tumors, covering the whole surface of the kidney and resulting in a marked enlargement of the kidney, were observed at day 10 after tumor cell grafting. Daily treatment with PMEA at 25 mg/kg/day afforded a marked reduction in tumor size (i.e., smaller tumors and slight, if any, enlargement of the kidney). Increasing the PMEA dose to 50, 100 or 250 mg/kglday resulted in a gradual increase of the antitumor effect of the compound. At the highest dose tested, i.e., 250 mg/kg/day, PMEA completely suppressed tumor growth. The antitumor activity of PMEA persisted for at least 10 days after termination of drug treatment. In addition, delayed treatment with PMEA at a dose of 200 mg/kg/day, started at a time point where choriocarcinoma tumors had already developed, stopped further growth and even induced regression of the tumors. PMPA, a closely related structural analogue of PMEA, failed to inhibit choriocarcinoma tumor growth. This observation points to the specificity of PMEA as an antitumor agent. In view of our findings, the therapeutic potential of PMEA for the treatment of neoplastic diseases appears to merit further investigation.
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PMID:Potent antitumor activity of the acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine in choriocarcinoma-bearing rats. 959 Jan 39

Nasopharyngeal carcinoma (NPC) is universally associated with EBV infection. We have shown that the phosphonated nucleoside analog, (S)-1-[3-hydroxy-2-(phosphonylmethoxy)-propyl]cytosine (HPMPC) strongly inhibits growth of NPC xenografts in nude mice by causing apoptosis (J. Neyts et al., Cancer Res., 58, 384-388, 1998). We, therefore, tested two additional members of this drug family that have different degrees of antiviral activity, 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) and 9-2-(R)-(phosphonomethoxy)propyladenine (PMPA). Intratumoral injection of PMEA (75 microl of 2% solution) in C15 NPC xenografts, which are latently infected with EBV, slowed tumor growth moderately, whereas PMPA (75 microl of 2% solution) slowed tumor growth only marginally. Compared with the previous results showing complete regression of tumor, PMEA had less antitumoral effect than HPMPC, and PMPA had the least. After 4 weeks of preventive treatment, tumors formed in 12.5, 50, and 100% of mice treated with HPMPC, PMEA, and PMPA, respectively, in contrast to the development of tumors in all of the PBS-treated control mice. We also investigated the effect of each drug on the EBV-positive epithelial cell line NPC-KT in vitro. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed inhibition of growth of NPC-KT cells by HPMPC and PMEA, but not by PMPA, which correlates with the results observed in tumor xenografts. Growth inhibition was attributable to induction of apoptosis in NPC-KT cells as indicated by a DNA fragmentation assay. Cleavage of poly(ADP-ribose) polymerase after treatment of NPC-KT cells with HPMPC was observed, which suggested that the apoptosis may be mediated by caspase(s). The apoptotic effects of the drugs are independent of any effects on EBV DNA polymerase, which is not expressed in these latently infected NPCs. These results suggest that HPMPC as well as PMEA could provide an adjunctive treatment for NPC.
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PMID:Prevention and inhibition of nasopharyngeal carcinoma growth by antiviral phosphonated nucleoside analogs. 1169 6