Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At present more than 70 human papillomaviruses (HPV) genotypes have been described and each shows a predilection for a cutaneous or mucosal surface. There is a strong association between infection with specific genital viruses (i.e., types 16 and 18) and the development of cervical cancer. Thus, intervention with the natural history of HPV infection in the genital tract may form the basis for an effective anticancer strategy. We have shown that treatment of cell lines derived from human cervical carcinomas [i.e., SiHa and CaSki (HPV-16-positive)] and HeLa (HPV-18-positive)] with HPMPC (cidofovir) results in a concentration- and time-dependent inhibition of cell proliferation. We report here the effects of HPMPC on the growth of cervical carcinoma (SiHa) xenografts in athymic nude mice. Athymic mice between the age of 6 and 8 weeks were injected SC with 5 to 10x10(6) cells. Once tumors were established, the mice were injected with PBS (placebo), HPMPC, or cytarabine (AraC) at the tumor site. Animals that were injected intratumorally with HPMPC at a dose of 5 mg/ml (0.25 mg/injection) or 10 mg/ml (0.5 mg/injection) three or five times per week, once daily, during 4 weeks showed a statistically significant reduction in tumor size compared to the placebo group or AraC group. However, when HMPC was administered topically (as a cream) or systemically (intraperitoneally), no reduction of tumor growth was observed at nontoxic concentrations, suggesting that a high local concentration of HPMPC is required to achieve a significant decrease of tumor growth.
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PMID:Inhibiting effects of cidofovir (HPMPC) on the growth of the human cervical carcinoma (SiHa) xenografts in athymic nude mice. 1033 56

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