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[PMID]:10769653
[Au] Autor:Khandaker MH; Kadhim SA; Ichim TE; Howson-Jan K; Chin J; Singhal SK
[Ad] Endereço:Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
[Ti] Título:Prevention of bladder tumor formation in mice by a novel bone marrow-derived factor, reptimed.
[So] Source:Anticancer Res;20(1A):183-9, 2000 Jan-Feb.
[Is] ISSN:0250-7005
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Reptimed is a novel, species-conserved, bone marrow-derived molecule which possesses anti-neoplastic activity. Previously, we established an orthotopic murine bladder tumor (MBT-2) model and reported accurate documentation of the presence and the extent of intravesical involvement of bladder tumor implants using magnetic resonance imaging (MRI) (1). Herein, we investigated the activity of exogenously administered Reptimed in the MBT-2 model. MATERIALS AND METHODS: Intravesicular and intraperitoneal administration of Reptimed concurrently with and following transurethral tumor cell implantation was performed and MBT-2 tumor response was assessed at several time points post tumor implant. RESULTS: Serial MRI scans of Reptimed-treated mice at days 14 to 33 post tumor transplant revealed significant inhibition of bladder tumor growth with no significant tumor growth observed by MRI on day 33 post-implant. The corresponding histological examination of the whole mount bladder sections revealed similar inhibitory effects of Reptimed with respect to the topography and depth of intravesical tumor involvement. In contrast, control, untreated bladders revealed extensive exophytic tumors with deeply invasive transitional cell carcinoma. CONCLUSIONS: These studies demonstrate the anti-tumor effect of Reptimed and highlight its importance as a potential therapy for cancer.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Carcinoma de Células de Transição/prevenção & controle
Inibidores do Crescimento/uso terapêutico
Polissacarídeos/uso terapêutico
Neoplasias da Bexiga Urinária/prevenção & controle
[Mh] Termos MeSH secundário: Administração Intravesical
Animais
Antineoplásicos/administração & dosagem
Antineoplásicos/isolamento & purificação
Antineoplásicos/farmacologia
Medula Óssea/química
Carcinoma de Células de Transição/induzido quimicamente
Carcinoma de Células de Transição/patologia
Divisão Celular/efeitos dos fármacos
FANFT
Feminino
Inibidores do Crescimento/administração & dosagem
Inibidores do Crescimento/isolamento & purificação
Inibidores do Crescimento/farmacologia
Células-Tronco Hematopoéticas/química
Injeções Intraperitoneais
Imagem por Ressonância Magnética
Camundongos
Camundongos Endogâmicos C3H
Invasividade Neoplásica
Transplante de Neoplasias
Polissacarídeos/administração & dosagem
Polissacarídeos/isolamento & purificação
Polissacarídeos/farmacologia
Ratos
Ratos Endogâmicos WF
Transplante Heterotópico
Neoplasias da Bexiga Urinária/induzido quimicamente
Neoplasias da Bexiga Urinária/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Growth Inhibitors); 0 (Polysaccharides); 0 (reptimed); 7N99PZG62O (FANFT)
[Em] Mês de entrada:0005
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:000419
[St] Status:MEDLINE


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[PMID]:9819896
[Au] Autor:Kessel D; Hampton J; Fingar V; Morgan A
[Ad] Endereço:Wayne State University, School of Medicine, Detroit, MI 48021, USA. dhkessel@med.wayne.edu
[Ti] Título:Tumor versus vascular photodamage in a rat tumor model.
[So] Source:J Photochem Photobiol B;45(1):25-7, 1998 Aug 21.
[Is] ISSN:1011-1344
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The [4-(5-nitro-2-furyl)-2-thiazoyl] formamide (FANFT)-induced urothelial tumor in the rat is found to express the mdr gene. The resulting multidrug resistance (MDR) phenotype results in the expression of an outward transport system that prevents cellular accumulation of certain weakly cationic agents. Among the latter is a photosensitizer with known efficacy for the FANFT tumor, the copper benzochlorin iminium salt. FANFT cells are protected from direct cell kill mediated by this drug, suggesting that the substantial delay in tumor regrowth from this tumor/sensitizer combination can be attributed to vascular effects.
[Mh] Termos MeSH primário: Deuteroporfirinas/farmacocinética
Resistência a Múltiplos Medicamentos/genética
Iminas/farmacocinética
Fármacos Fotossensibilizantes/farmacocinética
Neoplasias Urológicas/patologia
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese
Animais
Transporte Biológico
Sobrevivência Celular
FANFT
Fotoquímica
Ratos
Células Tumorais Cultivadas
Neoplasias Urológicas/induzido quimicamente
Neoplasias Urológicas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Deuteroporphyrins); 0 (Imines); 0 (Photosensitizing Agents); 145582-83-8 (copper benzochlorin); 7N99PZG62O (FANFT)
[Em] Mês de entrada:9812
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:981120
[St] Status:MEDLINE


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[PMID]:8640944
[Au] Autor:Ogawa K; Sun TT; Cohen SM
[Ad] Endereço:Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135, USA.
[Ti] Título:Analysis of differentiation-associated proteins in rat bladder carcinogenesis.
[So] Source:Carcinogenesis;17(5):961-5, 1996 May.
[Is] ISSN:0143-3334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Uroplakins are the major integral membrane proteins synthesized in terminally differentiated, superficial urothelial cells. Alteration of cell differentiation during rat urinary bladder carcinogenesis was analyzed immunohistochemically for the expression of uroplakins. Expression of uroplakins was compared in N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT)-, uracil-, sodium saccharin- or sodium ascorbate-induced urothelial simple hyperplasia, papillary-nodular hyperplasia, papilloma and carcinoma. In controls, uroplakins were located only in superficial cells, especially the luminal surface membrane. In FANFT-induced hyperplasia, including simple hyperplasia, intermediate cells also stained and the staining pattern was disorderly and intermittent. In uracil-induced simple hyperplasia, intermediate cells were stained but in an orderly fashion. In sodium saccharin- or sodium ascorbate-induced simple hyperplasia, superficial cells were swollen but alterations were not observed in the staining pattern. In carcinoma induced by FANFT and uracil, uroplakin expression was very disorderly and focal, usually with no expression on surface cells. It appears that disorderly differentiation is an index of bladder malignancy and is an early event in FANFT-induced lesions but a late event in uracil-, sodium saccharin- and sodium ascorbate-induced lesions.
[Mh] Termos MeSH primário: Glicoproteínas de Membrana/análise
Proteínas de Membrana/análise
Neoplasias da Bexiga Urinária/química
[Mh] Termos MeSH secundário: Animais
FANFT/toxicidade
Masculino
Ratos
Ratos Endogâmicos F344
Sacarina/toxicidade
Uracila/toxicidade
Neoplasias da Bexiga Urinária/induzido quimicamente
Uroplaquina II
Uroplaquina III
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Membrane Glycoproteins); 0 (Membrane Proteins); 0 (Uroplakin II); 0 (Uroplakin III); 56HH86ZVCT (Uracil); 7N99PZG62O (FANFT); FST467XS7D (Saccharin)
[Em] Mês de entrada:9607
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:960501
[St] Status:MEDLINE


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[PMID]:7784639
[Au] Autor:Cohen SM
[Ad] Endereço:Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135, USA.
[Ti] Título:Human relevance of animal carcinogenicity studies.
[So] Source:Regul Toxicol Pharmacol;21(1):75-80; discussion 81-6, 1995 Feb.
[Is] ISSN:0273-2300
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Extrapolation of results from rodent bioassays involving high-dose exposures to possible carcinogenic risk in humans exposed to low doses is based on the assumptions of species relevance and high- to low-dose extrapolation. For genotoxic chemicals, such as 2-acetylaminofluorene and N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide, these assumptions appear to be appropriate, although the dose response can be greatly modified by cell proliferation effects of these chemicals at high doses. In contrast, nongenotoxic chemicals, such as chemicals causing urinary calculi or sodium saccharin and related sodium and potassium salts, frequently are carcinogenic only at high doses and/or only in specific species. Consequently, for extrapolation of results for nongenotoxic chemicals these assumptions may not be appropriate.
[Mh] Termos MeSH primário: Testes de Carcinogenicidade
Modelos Animais de Doenças
[Mh] Termos MeSH secundário: 2-Acetilaminofluoreno/toxicidade
Animais
Cocarcinogênese
FANFT/toxicidade
Feminino
Seres Humanos
Masculino
Camundongos
Ratos
Ratos Endogâmicos F344
Sacarina/toxicidade
Cálculos Urinários/induzido quimicamente
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.; REVIEW
[Nm] Nome de substância:
7N99PZG62O (FANFT); 9M98QLJ2DL (2-Acetylaminofluorene); FST467XS7D (Saccharin)
[Em] Mês de entrada:9507
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:950201
[St] Status:MEDLINE


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[PMID]:7614682
[Au] Autor:Holmäng S; Cano M; Grenabo L; Hedelin H; Johansson SL
[Ad] Endereço:Department of Urology, University of Göteborg, Sweden.
[Ti] Título:Effect of indomethacin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced urinary tract carcinogenesis.
[So] Source:Carcinogenesis;16(7):1493-8, 1995 Jul.
[Is] ISSN:0143-3334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The effects of indomethacin on the urinary bladder and renal pelvis in rats treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) were studied. Two hundred female Sprague-Dawley rats were divided into four groups. Group 1 received control diet without added chemicals. Group 2 was treated with indomethacin (1 mg/kg per day) in the drinking water throughout the experiment. Groups 3 and 4 received 0.2% FANFT in the diet for seven weeks followed by control diet. In addition to FANFT, Group 4 received indomethacin, 1 mg/kg per day, for the entire experiment. The rats were sacrificed after 92 weeks. There were no urothelial tumors in the control group, one renal pelvic tumor in the indomethacin group, 4 tumors in the FANFT group and 10 urothelial tumors in the FANFT + indomethacin group. The difference between Groups 3 and 4 was statistically significant (P < 0.05). Moderate and severe hyperplasia of the renal pelvic and papillary epithelium was found in 15 of 48 rats in Group 2 (indomethacin only) as compared with 6 of 49 control rats (P < 0.05). Moderate and severe hyperplasia was equally frequent in Groups 3 and 4 (14 and 17 animals in each group, respectively). Twenty-four rats in Group 2 had mammary tumors as compared to 12 animals in Group 1 (P < 0.01). Five of the tumors in Group 2 were adenocarcinomas. There was no difference between the number of mammary tumors in Groups 3 and 4 (36 and 32 animals in each group, respectively). The results suggest that indomethacin enhances FANFT-induced urinary tract carcinogenesis. Indomethacin also seems to exert some tumorigenic activity in the mammary gland.
[Mh] Termos MeSH primário: Cocarcinogênese
FANFT/toxicidade
Indometacina/toxicidade
Neoplasias Urológicas/induzido quimicamente
[Mh] Termos MeSH secundário: Animais
Peso Corporal/efeitos dos fármacos
Carcinoma de Células Escamosas/induzido quimicamente
Carcinoma de Células de Transição/induzido quimicamente
Sinergismo Farmacológico
Feminino
Hematúria/induzido quimicamente
Pelve Renal/efeitos dos fármacos
Neoplasias Mamárias Experimentais/induzido quimicamente
Ratos
Ratos Sprague-Dawley
Neoplasias da Bexiga Urinária/induzido quimicamente
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
7N99PZG62O (FANFT); XXE1CET956 (Indomethacin)
[Em] Mês de entrada:9508
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:950701
[St] Status:MEDLINE


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[PMID]:8048791
[Au] Autor:Hampton JA; Goldblatt PJ; Selman SH
[Ad] Endereço:Department of Urology, Medical College of Ohio, Toledo 43699.
[Ti] Título:Photodynamic therapy: a new modality for the treatment of cancer.
[So] Source:Ann Clin Lab Sci;24(3):203-10, 1994 May-Jun.
[Is] ISSN:0091-7370
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Photodynamic therapy is a promising new modality for the treatment of neoplastic disease. Currently, Photofrin is the only photosensitizer approved for the treatment of human cancers. In the search for new, chemically pure second generation photosensitizing agents which absorb in the deep red region of the visible spectrum, a novel and unique photosensitizer, CDS1, an iminium salt of copper octaethylbenzochlorin, was developed. This new photosensitizer is chemically pure, cationic, and possesses a strong (epsilon = 35000 M-1.cm-1) absorption peak at 750 nm (in dichloromethane). With copper in the aromatic cavity and a triplet lifetime which is not measurable (< 20 nsec), the photodynamic activity of CDS1 was unexpected. Preliminary in vitro and in vivo animal studies with a transplantable urothelial tumor indicate that CDS1 is an effective photosensitizing agent when used in conjunction with a broad band xenon arc light source or a low frequency, high peak power pulsed alexandrite laser.
[Mh] Termos MeSH primário: Deuteroporfirinas/uso terapêutico
Iminas/uso terapêutico
Fotoquimioterapia
Fármacos Fotossensibilizantes/uso terapêutico
Neoplasias Urológicas/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
FANFT
Masculino
Transplante de Neoplasias
Ratos
Ratos Endogâmicos F344
Células Tumorais Cultivadas
Neoplasias Urológicas/induzido quimicamente
Neoplasias Urológicas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Deuteroporphyrins); 0 (Imines); 0 (Photosensitizing Agents); 145582-83-8 (copper benzochlorin); 7N99PZG62O (FANFT)
[Em] Mês de entrada:9408
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:940501
[St] Status:MEDLINE


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[PMID]:7915641
[Au] Autor:Mann AM; Asamoto M; Masui T; Macatee T; Eklund SH; Cohen SM
[Ad] Endereço:Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135.
[Ti] Título:neu is not involved in N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced bladder carcinoma or 2-amino-4-(5-nitro-2-furyl)thiazole transformation of rat bladder epithelial cells.
[So] Source:Cancer Lett;84(2):125-31, 1994 Sep 15.
[Is] ISSN:0304-3835
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Enhanced c-erbB-2/neu expression has been linked with a poor prognosis in human bladder cancer. Previous reports have shown that a point mutation at nucleotide T2012 in the coding region of the transmembrane domain of the rat gene is sufficient to confer transformation potential on this gene. We examined the comparative levels of p185neu as well as the sequence around the hotspot (T2012) of the neu gene of rat bladder cells transformed by 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) or established in culture from N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT)-induced rat bladder tumors. We concluded that increased p185neu expression did not correlate significantly with tumorigenicity. No alterations in nucleotide sequences of the neu gene were observed in either in vitro model.
[Mh] Termos MeSH primário: Proteínas Proto-Oncogênicas/genética
Receptor do Fator de Crescimento Epidérmico/genética
Neoplasias da Bexiga Urinária/genética
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Southern Blotting
Carcinógenos
Transformação Celular Neoplásica
Células Cultivadas
FANFT/análogos & derivados
Expressão Gênica
Dados de Sequência Molecular
Ratos
Receptor ErbB-2
Bexiga Urinária/metabolismo
Neoplasias da Bexiga Urinária/induzido quimicamente
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Carcinogens); 0 (Proto-Oncogene Proteins); 38514-71-5 (ANFT); 7N99PZG62O (FANFT); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:9410
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:940915
[St] Status:MEDLINE


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[PMID]:7915640
[Au] Autor:Mann AM; Asamoto M; Masui T; Macatee T; Eklund SH; Cohen SM
[Ad] Endereço:Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135.
[Ti] Título:Neu is not involved in N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide- induced bladder carcinoma or 2-amino-4-(5-nitro-2-furyl)thiazole transformation of rat bladder epithelial cells.
[So] Source:Cancer Lett;84(1):7-13, 1994 Aug 29.
[Is] ISSN:0304-3835
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Enhanced c-erbB-2/neu expression has been linked with a poor prognosis in human bladder cancer. Previous reports have shown that a point mutation at nucleotide T2012 in the coding region of the transmembrane domain of the rat gene is sufficient to confer transformation potential on this gene. We examined the comparative levels of p185neu as well as the sequence around the hotspot (T2012) of the neu gene of rat bladder cells transformed by 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) or established in culture from N-[-4-(-5-nitro-2-furyl)-2- thiazolyl]formamide (FANFT)-induced rat bladder tumors. We concluded that increased p185neu expression did not correlate significantly with tumorigenicity. No alterations in nucleotide sequences of the neu gene were observed in either in vitro model.
[Mh] Termos MeSH primário: Carcinoma de Células de Transição/induzido quimicamente
Carcinoma de Células de Transição/genética
Transformação Celular Neoplásica/efeitos dos fármacos
Transformação Celular Neoplásica/genética
Proteínas Proto-Oncogênicas/genética
Proteínas Proto-Oncogênicas/fisiologia
Receptor do Fator de Crescimento Epidérmico/genética
Receptor do Fator de Crescimento Epidérmico/fisiologia
Neoplasias da Bexiga Urinária/induzido quimicamente
Neoplasias da Bexiga Urinária/genética
[Mh] Termos MeSH secundário: Células 3T3
Animais
Sequência de Bases
Carcinoma de Células de Transição/metabolismo
Células Cultivadas
Epitélio/efeitos dos fármacos
Epitélio/patologia
Epitélio/fisiologia
FANFT/análogos & derivados
Expressão Gênica
Imuno-Histoquímica
Camundongos
Dados de Sequência Molecular
Mutação
Proteínas Proto-Oncogênicas/análise
Ratos
Ratos Endogâmicos F344
Receptor do Fator de Crescimento Epidérmico/análise
Receptor ErbB-2
Bexiga Urinária/efeitos dos fármacos
Bexiga Urinária/patologia
Bexiga Urinária/fisiologia
Neoplasias da Bexiga Urinária/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Gs] Símbolo de gene:neu
[Nm] Nome de substância:
0 (Proto-Oncogene Proteins); 38514-71-5 (ANFT); 7N99PZG62O (FANFT); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:9410
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:940829
[St] Status:MEDLINE


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[PMID]:8498082
[Au] Autor:Dawley RM; Lakshmi VM; Babu SR; Zenser TV; Davis BB
[Ad] Endereço:VA Medical Center, St Louis, MO.
[Ti] Título:Liver NADPH-dependent oxidation of the 5-nitrofurans, FANFT and ANFT, by guinea pig and rat.
[So] Source:Xenobiotica;23(2):193-203, 1993 Feb.
[Is] ISSN:0049-8254
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:1. Oxidative metabolism of the bladder carcinogens FANFT/ANFT was examined in vitro in guinea pig (resistant species) relative to rat (susceptible species). 2. The total rate of ANFT hepatic metabolism by guinea pig (soluble metabolites plus protein bound, 354 pmol/min per mg protein) was approx. 4 times that in rat. 3. The total rate of FANFT metabolism was similar in both species and approx. one-quarter that for ANFT in guinea pig. In rat, the rate of total metabolism of FANFT and ANFT was similar. 4. Cytochrome P450 inhibitors, 2,4-dichloro-6-phenylphenoxyethylamine, 7,8-benzoflavone, and n-octylamine largely inhibited metabolism in guinea pig, but had little effect in rat. 5. H.p.l.c. analysis of ANFT metabolites indicated distinctly different products in guinea pig compared to rat. 7,8-Benzoflavone decreased metabolite formation by 80% in guinea pig, but only 30% in rat. 6. Flavin-dependent monooxygenases may participate in metabolism of these carcinogens in rat, but not guinea pig. 7. Because ANFT is thought to be a more proximate carcinogen than FANFT, the increased rate of ANFT metabolism and the formation of different products in guinea pig compared to rat may partially explain the resistance of guinea pig to FANFT-induced bladder cancer.
[Mh] Termos MeSH primário: Carcinógenos/metabolismo
FANFT/análogos & derivados
FANFT/metabolismo
Fígado/metabolismo
NADP/metabolismo
[Mh] Termos MeSH secundário: Animais
DNA/metabolismo
Inibidores Enzimáticos/farmacologia
Cobaias
Rim/metabolismo
Fígado/enzimologia
Masculino
Microssomos Hepáticos/enzimologia
Especificidade de Órgãos
Oxirredução
Ligação Proteica/efeitos dos fármacos
Ratos
Ratos Endogâmicos F344
Neoplasias da Bexiga Urinária/induzido quimicamente
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Carcinogens); 0 (Enzyme Inhibitors); 38514-71-5 (ANFT); 53-59-8 (NADP); 7N99PZG62O (FANFT); 9007-49-2 (DNA)
[Em] Mês de entrada:9306
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:930201
[St] Status:MEDLINE


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[PMID]:8331577
[Au] Autor:Lakshmi VM; Zenser TV; Mattammal MB; Davis BB
[Ad] Endereço:Veterans Administration Medical Center, St. Louis, Missouri.
[Ti] Título:Phenylbutazone peroxidatic metabolism and conjugation.
[So] Source:J Pharmacol Exp Ther;266(1):81-8, 1993 Jul.
[Is] ISSN:0022-3565
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phenylbutazone, a nonsteroidal anti-inflammatory drug, elicits therapeutic as well as toxic effects by unknown pathways. Phenylbutazone was shown to form a conjugate with the heterocyclic amine bladder carcinogen 2-amino-4-(5-nitro-2-furyl)-thiazole (ANFT). To understand further the reactivity of these compounds, this study was conducted to identify the conjugate formed and determine the mechanism of conjugate formation. Both prostaglandin H synthase and horseradish peroxidase catalyzed conjugate formation. This conjugate was identified by 1H-NMR to be 4-[2-amino-4-(5-nitro-2-furyl)-5-thiazolyl]-4-butyl-1,2-diphenyl-3,5- pyrazolidinedione. Phenylbutazone-mediated oxygen uptake was inhibited by ANFT (0.1 mM) and the spin traps 5,5-dimethyl-1-pyrroline-N-oxide (200 mM) and tert-nitrosobutane (4 mM). By contrast, phenol (0.005 to 0.25 mM) and aminopyrine (0.4 mM) stimulated oxygen uptake. None of these agents mediated oxygen uptake in the absence of phenylbutazone. Conjugate formation was significantly increased by phenol (0.005-0.25 mM) and aminopyrine (0.4 mM), as well as in the absence of oxygen. Conjugate formation was inhibited by 5,5-dimethyl-1-pyrroline-N-oxide (200 mM), tert-nitrosobutane (4 mM), ascorbic acid (2 mM), and 95% oxygen. Horseradish peroxidase initiated conjugate formation at much lower concentrations than it metabolized ANFT. The stoichiometric relationship between phenylbutazone and ANFT, with respect to conjugate formation, was complex. With the concentration of ANFT fixed at 0.05 mM, phenylbutazone exhibited saturation kinetics with a Km of 0.2 mM. In contrast, saturation kinetics were not observed with ANFT.Km values for ANFT varied with the concentration of phenylbutazone used.(ABSTRACT TRUNCATED AT 250 WORDS)
[Mh] Termos MeSH primário: Carcinógenos/metabolismo
FANFT/análogos & derivados
Fenilbutazona/metabolismo
[Mh] Termos MeSH secundário: Biotransformação
Carcinógenos/farmacocinética
Cromatografia Líquida de Alta Pressão
FANFT/metabolismo
FANFT/farmacocinética
Peroxidase do Rábano Silvestre/metabolismo
Cinética
Peróxidos/metabolismo
Ligação Proteica
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Carcinogens); 0 (Peroxides); 38514-71-5 (ANFT); 7N99PZG62O (FANFT); EC 1.11.1.- (Horseradish Peroxidase); GN5P7K3T8S (Phenylbutazone)
[Em] Mês de entrada:9308
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:930701
[St] Status:MEDLINE



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