Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of butoctamide (N-(2-ethylhexyl)-3-hydroxybutyramide, L-2) on the antitumor activity of 6-mercaptopurine (6-MP) against Ehrlich solid tumors in mice were investigated. No change was observed in tumor growth after either oral or intraperitoneal administration of butoctamide (100 mg/kg/day X 7). This drug increased the activity of a low dose of 6-MP (2.5 approximately 10 mg/kg/day. i.p., X 7), but did not change the activity of a high dose of 6-MP (40 approximately 80 mg/kg/day, i.p., X 7). The antitumor activity of thioinosine (6-MP riboside) was similarly increased by administration of butoctamide (100 mg/kg/day, i.p., X 7). On the other hand, concomitant administration of butoctamide with cyclophosphamide, methotrexate, mitomycin C or adriamycin had no effect on the activity of these anticancer drugs. In butoctamide (100 mg/kg/day, i.p., X 7)-treated mice, the antitumor activities of a single administration of 6-MP and cyclophosphamide were not increased. Butoctamide stimulated the hypoxanthine-guanine phosphoribosyltransferase activity and inhibited the xanthine oxidase activity of mouse liver, to a certain degree as compared to controls. Butoctamide may promote conversion from 6 MP to thioinosinic acid monophosphate to a biologically active state, rather than to thiouric acid or hypoxanthine which would be inactive.
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PMID:[Butoctamide enhancement of the antitumor activity of 6-mercaptopurine on Ehrlich solid tumors in mice (author's transl)]. 689 82

2-methoxyestradiol (2-MeOE(2)) is an endogenous metabolite of 17beta-estradiol and a proposed inhibitor of tumor growth and angiogenesis. However, 2-MeOE(2) is also an inhibitor of microtubule assembly and other microtubule inhibitors, e.g. colcemid and diethylstilbestrol, induce aneuploidy and cell transformation in cultured mammalian cells. To assess the in vitro carcinogenicity and related activity of 2-MeOE(2), the abilities of this metabolite to induce cell transformation and genetic effects were studied simultaneously using Syrian hamster embryo (SHE) fibroblasts. Growth of these cells was reduced by treatment with 2-MeOE(2) at 0.1-1.0 microg/ml in a concentration-dependent manner. Treatment of SHE cells with 2-MeOE(2) at 0.3 or 1.0 microg/ml for 2-48 h also resulted in a concentration- and treatment time-related increase in the mitotic index and the percentage of multinucleated cells. Treatment with 2-MeOE(2) at 0.1-1.0 microg/ml for 48 h induced a statistically significant increase in the frequencies of morphological transformation of SHE cells in a concentration-dependent manner. A statistically significant increase in the frequencies of somatic mutations at the Na(+)/K(+) ATPase or hprt locus was also observed in cells treated with 2-MeOE(2) for 48 h at 0.1 or 0.3 microg/ml, respectively. Treatment of SHE cells with 2-MeOE(2) at 0.3 or 1.0 microg/ml for 24 h induced chromosome aberrations, mainly breaks, exchanges and chromosome pulverization. The incidence of chromosome aberrations was not affected by co-treatment with alpha-naphthoflavone, an inhibitor of 2-hydroxylase that inhibits oxidative conversion of 2-MeOE(2) to 2-hydroxyestradiol, but the incidence was slightly increased by co-treatment with L-ascorbic acid. Numerical chromosomal changes in the near diploid range and in the tetraploid and near tetraploid ranges were also detected in 2-MeOE(2)-treated cells. These findings indicate that 2-MeOE(2) has cell transforming and genotoxic activities in cultured mammalian cells and potential carcinogenic activity.
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PMID:Induction of mammalian cell transformation and genotoxicity by 2-methoxyestradiol, an endogenous metabolite of estrogen. 1075 10

Purpose: To further enhance the antitumor efficacy through targeted delivery, DTX loaded lipid-based-nanosuspensions (DTX-LNS) were prepared and functionalized by PEGylation or NGR modification to develop DSPE-PEG2000 modified DTX-LNS (P-DTX-LNS) or DSPE-PEG2000-NGR modified DTX-LNS (N-DTX-LNS), respectively. Methods: Based on our previous work, functionalized DTX-LNS including P-DTX-LNS and N-DTX-LNS were prepared using thin-film hydration, and then characterized. Release behavior, stability in vitro, cytotoxicity and cellular uptake of functionalized LNS were observed. To demonstrate tumor targeting efficiency of functionalized DTX-LNS, in vivo real-time and ex vivo imaging study were conducted. Furthermore, therapeutic efficacy in vivo was evaluated in an H22-bearing mice model. Results: Functionalized DTX-LNS 100-110 nm in diameter were successfully prepared and exhibited good stability under various conditions. In vitro release studies demonstrated that DTX was released from functionalized DTX-LNS steadily and reached approximately 95% at 48 hrs. Functionalized DTX-LNS showed dose-dependent cytotoxicity and time-dependent internalization in human hepatocellular liver carcinoma cells (HepG2) cells. In vivo real-time and ex vivo imaging results indicated that tumor targeting efficiencies of P-DiR-LNS and N-DiR-LNS were 29.9% and 34.3%, respectively. Moreover, evaluations of in vivo antitumor efficacy indicated that functionalized DTX-LNS effectively inhibited tumor growth with low toxicity. Conclusion: The functionalized LNS exhibited suitable particle size, nearly spherical structure, enough drug loading and great potentials for large-scale production. The results in vitro and in vivo demonstrated that functionalized LNS could realize tumor targeting and antitumor efficacy. Consequently, functionalized DTX-LNS could be expected to be used for tumor targeting therapy.
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PMID:Functionalized docetaxel-loaded lipid-based-nanosuspensions to enhance antitumor efficacy in vivo. 3111 90