hydroxylamine/kanker

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Hydroxylamine effects on cryptogenic neoplasm development in C3H mice.

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The effect of administration of hydroxylamine (HA) to male and female mice was studied because of reports suggesting an anticarcinogenic effect and an enhancement of lifespan. In this study, two C3H sublines were used: the C3H/HeN which carries a germinal provirus of the mouse mammary tumor virus

Detection of a new N-oxidized metabolite of flutamide, N-[4-nitro-3-(trifluoromethyl)phenyl]hydroxylamine, in human liver microsomes and urine of prostate cancer patients.

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Flutamide (2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-propanamide), a nonsteroidal antiandrogen, is used in the treatment of prostate cancer but is occasionally associated with hepatic dysfunction. In the present study, the metabolism of flutamide including the formation of the possible reactive

An EPR Study Using Cyclic Hydroxylamines To Assess The Level of Mitochondrial ROS in Superinvasive Cancer Cells

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It has been proposed that a mitochondrial switch involving a high mitochondrial superoxide production is associated with cancer metastasis. We here report an EPR analysis of ROS production using cyclic hydroxylamines in superinvasive SiHa-F3 compared with less invasive SiHa wild-type human cervix

uvrB gene deletion enhances SOS chromotest sensitivity for nitroreductases that preferentially generate the 4-hydroxylamine metabolite of the anti-cancer prodrug CB1954.

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CB1954 is an anti-cancer prodrug that can be reduced at either of two nitro groups to form cytotoxic metabolites. We describe here two efficient and previously uncharacterized nitroreductases, YfkO from Bacillus subtilis which reduces CB1954 exclusively at the 4-NO(2) position, and NfsA from

[Effects of peroxisome proliferator-activated receptor γ-toll-like receptor 4-tumor necrosis factor-α targeted pathway on hyperglycemia induced myocardium inflammation and oxidative stress].

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OBJECTIVE To investigate the potential effects and mechanism on peroxisome proliferator-activated receptor γ-toll-like receptor 4-tumor necrosis factor-α (PPARγ-TLR4-TNF-α) targeted pathway on hyperglycemia induced myocardium inflammation and oxidative stress. METHODS Thirty-two Japanese healthy

Reduction of aromatic and heterocyclic aromatic N-hydroxylamines by human cytochrome P450 2S1.

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Many aromatic amines and heterocyclic aromatic amines (HAAs) are known carcinogens for animals, and there is also strong evidence of some in human cancer. The activation of these compounds, including some arylamine drugs, involves N-hydroxylation, usually by cytochrome P450 enzymes (P450) in Family

CB 1954: from the Walker tumor to NQO2 and VDEPT.

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CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] has been the subject of continued interest for over 30 years. As an anti-cancer agent, it represents one of the very few examples of a compound that shows real anti-tumor selectivity. Unfortunately, for the treatment of human disease, this anti-tumor

In vitro and in vivo anti-tumor activity of L-glutamic acid gamma-monohydroxamate against L1210 leukemia and B16 melanoma.

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A glutamine analogue, L-glutamic acid gamma-monohydroxamate (GAH) demonstrated complete cytotoxicity against L1210 cells in culture and marked anti-tumoral activity in vivo against L1210 leukemia and B16 melanoma. In vitro, GAH caused concentration-dependent inhibition of L1210 cell growth, with

Application of a microfluidic reactor for screening cancer prodrug activation using silica-immobilized nitrobenzene nitroreductase.

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The nitroreductase-catalyzed conversion of a strong electron-withdrawing nitro group to the corresponding electron-donating hydroxylamine is useful in a variety of biotechnological applications. Activation of prodrugs for cancer treatments or antibiotic therapy are the most common applications.

Aerobic nitroreduction by flavoproteins: enzyme structure, mechanisms and role in cancer chemotherapy.

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NQO1 (DT-diaphorase) and its truncated isoenzyme, the metalloenzyme NQO2, can reduce quinone substrates by two-electron transfer. While NQO1 is a known detoxification enzyme, the function of NQO2 is less well understood. Both rat NQO1 and human NQO2 reductively bioactivate the dinitroarene CB 1954

Synthesis and NMR characterization of hydroxyurea and mesylglycol glycoconjugates as drug candidates for targeted cancer chemotherapy.

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Tumor targeting of glycoconjugated antineoplastic agents is a strategy currently under investigation for cancer chemotherapy. We have synthesized the glucosides and galactosides of the clinically established drug hydroxyurea and of mesylglycol, the reactive moiety of the anticancer drug busulfan.

Tumor necrosis factor alpha modifies agonist-dependent responses in human neutrophils by inducing the synthesis and myristoylation of a specific protein kinase C substrate.

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Tumor necrosis factor alpha (TNF-alpha) and bacterial lipopolysaccharide (LPS) induce the synthesis and cotranslational myristoylation of an 82-kDa specific protein kinase C substrate in human neutrophils. The myristic acid is covalently bound via a hydroxylamine-resistant amide linkage to the

Synthesis, antimicrobial and anti-cancer activities of some new N-ethyl, N-benzyl and N-benzoyl-3-indolyl heterocycles.

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A series of 1-(N-substituted-1H-indol-3-yl)-3-arylprop-2-ene-1-ones (2a, b-4a, b) were prepared and allowed to react with urea, thiourea or guanidine to give pyrimidine derivatives 5a, b-13a, b. Reaction of 2a, b-4a, b with ethyl acetoacetate in the presence of a base gave cyclohexanone derivatives

Safe and targeted anticancer efficacy of a novel class of antioxidant-conjugated difluorodiarylidenyl piperidones: differential cytotoxicity in healthy and cancer cells.

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The development of smart anticancer drugs that can selectively kill cancer cells while sparing the surrounding healthy tissues/cells is of paramount importance for safe and effective cancer therapy. We report a novel class of bifunctional compounds based on diarylidenyl piperidone (DAP) conjugated

DNA cross-links in human tumor cells exposed to the prodrug PR-104A: relationships to hypoxia, bioreductive metabolism, and cytotoxicity.

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PR-104, currently in clinical trial, is converted systemically to the dinitrobenzamide nitrogen mustard prodrug PR-104A, which is reduced selectively in hypoxic cells to cytotoxic hydroxylamine (PR-104H) and amine (PR-104M) metabolites. Here, we evaluate the roles of this reductive metabolism, and

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