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[PMID]:26027696
[Au] Autor:Lambert JM
[Ad] Endereço:ImmunoGen, Inc., 830 Winter Street, Waltham, Massachusetts 02451, United States.
[Ti] Título:Antibody-Drug Conjugates (ADCs): Magic Bullets at Last!
[So] Source:Mol Pharm;12(6):1701-2, 2015 Jun 01.
[Is] ISSN:1543-8392
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Compostos de Anilina
Compostos Azo
Química Farmacêutica
Clorambucila
Diálise
Fluoruracila
Soros Imunes
Mercaptopurina
Metotrexato
Compostos de Mostarda Nitrogenada
Pesquisa
Tetraciclina
Tiotepa
Raios Ultravioleta
Mostarda de Uracila
gama-Globulinas
[Pt] Tipo de publicação:EDITORIAL; COMMENT
[Nm] Nome de substância:
0 (Aniline Compounds); 0 (Azo Compounds); 0 (Immune Sera); 0 (Nitrogen Mustard Compounds); 0 (gamma-Globulins); 18D0SL7309 (Chlorambucil); 905Z5W3GKH (Thiotepa); E7WED276I5 (Mercaptopurine); F8VB5M810T (Tetracycline); U3P01618RT (Fluorouracil); W7KQ46GJ8U (Uracil Mustard); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150602
[St] Status:MEDLINE
[do] DOI:10.1021/acs.molpharmaceut.5b00302


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[PMID]:24195184
[Au] Autor:Kohorn EI
[Ad] Endereço:Yale University School of Medicine, Department of Obstetrics and Gynecoology, New Haven, USA. ernest.kohorn@yale.edu
[Ti] Título:Uracil mustard and 5-fluorouracil combination chemotherapy: a historic record.
[So] Source:Conn Med;77(7):433-6, 2013 Aug.
[Is] ISSN:0010-6178
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Uracil mustard and 5-fluorouracil (UM-FU) combination chemotherapy was used as one of the earliest combination chemotherapies in ovarian carcinoma from 1964 to 1971 at Yale New Haven Medical Center. METHODS: UM-FU was offered to patients with stage III and IV, histologically verified, ovarian carcinoma. Uracyl mustard was administered orally--1 mg/ kg, daily. 5-Fluorouracyl was administered every four weeks at 5 mg/kg for five days by intravenous infusion. RESULTS: Of a total 185 patients with ovarian cancer, 76 received UM-FU. Thirty-five patients had measurable disease. Fifteen (42%) showed objective response lasting three to 95 months, with decrease in size of masses and disappearance of ascites or hydrothorax. Their survival from diagnosis to death was 41 months. Twenty patients showed no response; their mean survival was 18 months. Three of the 76 patients who received UM-FU developed acute nonlymphocytic leukemia. CONCLUSION: UM-FU was effective in controlling ascites and hydrothorax and diminished intraabdominal masses. The discovery of adriamycin and then platinum led to more effective therapy and the use of uracil mustard was superseded. It is no longer available. The experience reported is of historic interest.
[Mh] Termos MeSH primário: Antineoplásicos/história
Protocolos de Quimioterapia Combinada Antineoplásica/história
Carcinoma/história
Fluoruracila/história
Neoplasias Ovarianas/história
Mostarda de Uracila/história
[Mh] Termos MeSH secundário: Adulto
Antineoplásicos/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Carcinoma/tratamento farmacológico
Carcinoma/patologia
Feminino
Fluoruracila/administração & dosagem
História do Século XX
Seres Humanos
Meia-Idade
Neoplasias Ovarianas/tratamento farmacológico
Neoplasias Ovarianas/patologia
Mostarda de Uracila/administração & dosagem
[Pt] Tipo de publicação:CASE REPORTS; HISTORICAL ARTICLE; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); U3P01618RT (Fluorouracil); W7KQ46GJ8U (Uracil Mustard)
[Em] Mês de entrada:1312
[Cu] Atualização por classe:131107
[Lr] Data última revisão:
131107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131108
[St] Status:MEDLINE


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[PMID]:20518307
[Au] Autor:Li YQ; Chai XY; Sun JF; Liu YH
[Ad] Endereço:Key Laboratory of Marine Bio-resourses Sustainable utilization, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510240, China. autumn.li@163.com
[Ti] Título:[Study on the chemical constituents qf Spongilla Wagner].
[So] Source:Zhong Yao Cai;33(1):60-1, 2010 Jan.
[Is] ISSN:1001-4454
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To study the chemical constituents in the fresh marine sponge Spongilla Wagner. METHODS: Compounds were separated and purified through various chromatographic methods and their structures were identified by spectroscopic data. RESULTS: Seven compounds were isolated and identified as 4-hydroxybenzoic acid (I), p-hydroxycinnamic acid (II), Pyrimidine-2, 4 (1H, 3H)-dione (III), Ferulic acid methyl ester (IV), Dodecyl ethers of glycerol (V), Tetracosane( VI). CONCLUSION: All compounds are isolated from this sponge for the first time.
[Mh] Termos MeSH primário: Ácidos Cumáricos/isolamento & purificação
Materia Medica/química
Parabenos/isolamento & purificação
Poríferos/química
[Mh] Termos MeSH secundário: Alcanos/química
Alcanos/isolamento & purificação
Animais
Cromatografia em Camada Delgada
Ácidos Cumáricos/química
Parabenos/química
Propionatos
Mostarda de Uracila/química
Mostarda de Uracila/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkanes); 0 (Coumaric Acids); 0 (Materia Medica); 0 (Parabens); 0 (Propionates); IBS9D1EU3J (trans-3-(4'-hydroxyphenyl)-2-propenoic acid); JG8Z55Y12H (4-hydroxybenzoic acid); W7KQ46GJ8U (Uracil Mustard); YQ5H1M1D7I (tetracosane)
[Em] Mês de entrada:1102
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100604
[St] Status:MEDLINE


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[PMID]:12166936
[Au] Autor:Baraldi PG; Romagnoli R; Guadix AE; Pineda de las Infantas MJ; Gallo MA; Espinosa A; Martinez A; Bingham JP; Hartley JA
[Ad] Endereço:Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy. pgb@ifeuniv.unife.it
[Ti] Título:Design, synthesis, and biological activity of hybrid compounds between uramustine and DNA minor groove binder distamycin A.
[So] Source:J Med Chem;45(17):3630-8, 2002 Aug 15.
[Is] ISSN:0022-2623
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The design, synthesis, characterization, DNA binding properties, and cytotoxic activity of a novel series of hybrids, namely, a molecular combination of the natural antibiotic distamycin A and the antineoplastic agent uramustine, are reported, and the structure-activity relationships are discussed. This homologous series 29-34 consisted of the minor groove binder distamycin A joined to uramustine (uracil mustard) by suitable aliphatic carboxylic acid moieties containing a flexible polymethylene chain that is variable in length [(CH(2))(n)(), where n = 1-6). All the hybrid compounds in this series exhibit enhanced activity compared to both distamycin A and uramustine derivatives 22-27 used for conjugation, giving IC(50) values in the range 7.26-0.07 microM following a 1 h exposure of human leukemic K562 cells, with maximal activity shown when n = 6. The distance between the uramustine and distamycin frame is crucial for the cytotoxicity, with compounds having linker lengths of four to six being at least 20-fold more cytotoxic than linker lengths one to three. Taq polymerase stop experiments demonstrated selective covalent binding of uramustine-distamycin hybrids to A/T rich DNA sequences, which was again more efficient with compounds 32-34 with a longer linker length. Two consequences can be derived from our study: (a) the distamycin moiety directs binding to the minor groove of A/T rich DNA sequences and, consequently, is responsible for the alkylation regioselectivity found in footprinting studies; (b) the higher flexibility due to a longer linker between the distamycin and uracil moieties allows the formation of complexes with the mustard moiety situated more deeply in the minor groove and, hence, with better alkylating properties.
[Mh] Termos MeSH primário: Antibacterianos/química
Antineoplásicos/síntese química
DNA/química
Distamicinas/química
Mostarda de Uracila/química
[Mh] Termos MeSH secundário: Antineoplásicos/química
Antineoplásicos/farmacologia
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Ligações de Hidrogênio
Modelos Moleculares
Relação Estrutura-Atividade
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antineoplastic Agents); 0 (Distamycins); 80O63P88IS (stallimycin); 9007-49-2 (DNA); W7KQ46GJ8U (Uracil Mustard)
[Em] Mês de entrada:0209
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:020809
[St] Status:MEDLINE


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[PMID]:10326707
[Au] Autor:Kennedy BJ; Torkelson JL; Torlakovic E
[Ad] Endereço:Department of Medicine, University of Minnesota Medical School, Fairview-University Medical Center, Minneapolis 55455, USA.
[Ti] Título:Uracil mustard revisited.
[So] Source:Cancer;85(10):2265-72, 1999 May 15.
[Is] ISSN:0008-543X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: A patient with diffuse large cell lymphoma who had a complete response lasting 35 years following a 3-day course of uracil mustard stimulated a recall review of patients treated with this oral alkylating agent. METHODS: Records of patients treated with uracil mustard between 1958 and 1970 were reviewed. A current histologic review according to the International Formulation was performed when possible. Total doses of uracil mustard were similar to those of mechlorethamine, although there were variations in the dose schedule. RESULTS: Employing criteria used over 25 years ago to evaluate patients' responses, the overall regression rate for 94 non-Hodgkin lymphoma patients was 69.2% (complete response [CR] 23.4%). Of 62 patients with Hodgkin disease, 69.4% responded (CR 9.7%). For 39 patients with chronic lymphatic leukemia, the combined complete and partial response rate was 74% (CR 7.7%). Thrombocytopenia was the primary toxicity. CONCLUSIONS: Uracil mustard is an unmarketed, inexpensive oral alkylating agent that has been effective in the treatment of patients with lymphoma, chronic lymphatic leukemia, and thrombocythemia. Perhaps it should be reevaluated.
[Mh] Termos MeSH primário: Antineoplásicos Alquilantes/uso terapêutico
Doença de Hodgkin/tratamento farmacológico
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
Linfoma não Hodgkin/tratamento farmacológico
Trombocitopenia/tratamento farmacológico
Mostarda de Uracila/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Antineoplásicos Alquilantes/efeitos adversos
Antineoplásicos Alquilantes/farmacologia
Doença de Hodgkin/patologia
Seres Humanos
Leucemia Linfocítica Crônica de Células B/patologia
Linfoma não Hodgkin/patologia
Meia-Idade
Estudos Retrospectivos
Análise de Sobrevida
Resultado do Tratamento
Mostarda de Uracila/efeitos adversos
Mostarda de Uracila/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents, Alkylating); W7KQ46GJ8U (Uracil Mustard)
[Em] Mês de entrada:9905
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:990518
[St] Status:MEDLINE


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[PMID]:8348078
[Au] Autor:Emilia G; Sacchi S; Temperani P; Longo R; Vecchi A
[Ad] Endereço:Second Medical Clinic, University of Modena, Italy.
[Ti] Título:Progression of essential thrombocythemia to blastic crisis via idiopathic myelofibrosis.
[So] Source:Leuk Lymphoma;9(4-5):423-6, 1993 Mar.
[Is] ISSN:1042-8194
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We report a 61-year-old man with essential thrombocythemia (ET) whose clinical course was followed for 12 years. The ET evolved into true idiopathic myelofibrosis (IM) 6 years after the initial diagnosis and progressed to myeloid blastic transformation 6 years later. The cytogenetic analysis showed a normal karyotype during the ET phase but subsequent analysis revealed an abnormal karyotype during the IM phase which evolved clonally at blastic crisis with constant involvement of chromosome 13q and chromosome 7. The close monitoring of essential events, using clinical, morphologic, immunologic and cytogenetic parameters, allowed us to carefully identify the transition from one chronic myeloproliferative disease (MPD) to another. This is only the second case reported showing a clinical evolution of this nature. The clinical and biological aspects of the disease are briefly discussed.
[Mh] Termos MeSH primário: Crise Blástica/patologia
Cromossomos Humanos Par 13/ultraestrutura
Cromossomos Humanos Par 7/ultraestrutura
Leucemia Mieloide Aguda/patologia
Mielofibrose Primária/patologia
Trombocitemia Essencial/patologia
[Mh] Termos MeSH secundário: Crise Blástica/genética
Terapia Combinada
Seguimentos
Seres Humanos
Hiperplasia
Imunofenotipagem
Cariotipagem
Leucemia Mieloide Aguda/genética
Leucemia Induzida por Radiação
Masculino
Megacariócitos/patologia
Meia-Idade
Células-Tronco Neoplásicas/patologia
Oncogenes
Mielofibrose Primária/genética
Radioterapia/efeitos adversos
Trombocitemia Essencial/tratamento farmacológico
Trombocitemia Essencial/genética
Trombocitemia Essencial/radioterapia
Mostarda de Uracila/efeitos adversos
Mostarda de Uracila/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
W7KQ46GJ8U (Uracil Mustard)
[Em] Mês de entrada:9309
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:930301
[St] Status:MEDLINE


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PubMed Central Texto completo
[PMID]:1620613
[Au] Autor:Hartley JA; Bingham JP; Souhami RL
[Ad] Endereço:Department of Oncology, University College and Middlesex School of Medicine, London, UK.
[Ti] Título:DNA sequence selectivity of guanine-N7 alkylation by nitrogen mustards is preserved in intact cells.
[So] Source:Nucleic Acids Res;20(12):3175-8, 1992 Jun 25.
[Is] ISSN:0305-1048
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Nitrogen mustard alkylating agents react with isolated DNA in a sequence selective manner, and the substituent attached to the drug reactive group can impose a distinct sequence preference. It is not clear however to what extent the observed DNA sequence preferences are preserved in intact cells. The highly reiterated sequence of human alpha DNA has been used to determine the sites of guanine-N7 alkylation following treatment of cells with three nitrogen mustards, mechlorethamine, uracil mustard and quinacrine mustard, known to react in isolated DNA with distinctly different sequence preferences. Alpha DNA from drug treated cells was extracted, purified, end-labeled, and a 296 base pair, singly end-labelled, fragment isolated. Following the quantitative conversion of alkylation sites to strand breaks the fragments were separated on DNA sequencing gels. Clear differences were observed between the alkylation patterns of the three compounds, and the selectivities were qualitatively similar to those predicted and observed in the same sequence alkylated in vitro. In particular the unique preferences of uracil and quinacrine mustards for 5'-PyGC-3' and 5'-GT/GPu-3' sequences, respectively, were preserved in intact cells suggesting that the pattern of sequence dependent reactivity is not grossly affected by the nuclear milieu.
[Mh] Termos MeSH primário: DNA/efeitos dos fármacos
Guanina/metabolismo
Mecloretamina/farmacologia
Mostarda de Quinacrina/farmacologia
Mostarda de Uracila/farmacologia
[Mh] Termos MeSH secundário: Alquilação
Sequência de Bases
DNA/metabolismo
Seres Humanos
Dados de Sequência Molecular
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
4213-45-0 (Quinacrine Mustard); 50D9XSG0VR (Mechlorethamine); 5Z93L87A1R (Guanine); 9007-49-2 (DNA); W7KQ46GJ8U (Uracil Mustard)
[Em] Mês de entrada:9208
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:920625
[St] Status:MEDLINE


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[PMID]:1327114
[Au] Autor:Doweyko AM; Mattes WB
[Ad] Endereço:CIBA-GEIGY Corporation, Environmental Health Center, Farmington, Connecticut 06032.
[Ti] Título:An application of 3D-QSAR to the analysis of the sequence specificity of DNA alkylation by uracil mustard.
[So] Source:Biochemistry;31(39):9388-92, 1992 Oct 06.
[Is] ISSN:0006-2960
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The sequence specificity of DNA alkylation by uracil mustard was examined using a novel three-dimensional QSAR method known as HASL, or the hypothetical active site lattice. The structures of a variety of 4-mer sequences obtained from pBR322 and SV40 were related to their degree of guanine-N7 alkylation by uracil mustard. The resulting correlations were found to point to a significant contribution from bases on the 3' side of the target guanine nucleotide. The HASL models derived from the analysis of 52 guanine-containing 4-mer sequences were used to highlight those atomic features in the favored TGCC sequence that were found most important in determining specificity. It was found that the NH2-O systems present in the two GC base pairs on the 3' side of the target guanine were significantly correlated to the degree of alkylation by uracil mustard. This finding is consistent with a prealkylation binding event occurring between these sites along the major groove and the uracil mustard O2/O4 system.
[Mh] Termos MeSH primário: DNA/química
Nucleotídeos de Guanina/química
Relação Estrutura-Atividade
Mostarda de Uracila/química
[Mh] Termos MeSH secundário: Alquilação
DNA Bacteriano/química
DNA Viral/química
Modelos Moleculares
Conformação de Ácido Nucleico
Plasmídeos/química
Sensibilidade e Especificidade
Vírus 40 dos Símios/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Bacterial); 0 (DNA, Viral); 0 (Guanine Nucleotides); 9007-49-2 (DNA); W7KQ46GJ8U (Uracil Mustard)
[Em] Mês de entrada:9211
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:921006
[St] Status:MEDLINE


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[PMID]:1751490
[Au] Autor:Hartley JA; Berardini M; Ponti M; Gibson NW; Thompson AS; Thurston DE; Hoey BM; Butler J
[Ad] Endereço:Department of Oncology, University College and Middlesex School of Medicine, London, U.K.
[Ti] Título:DNA cross-linking and sequence selectivity of aziridinylbenzoquinones: a unique reaction at 5'-GC-3' sequences with 2,5-diaziridinyl-1,4-benzoquinone upon reduction.
[So] Source:Biochemistry;30(50):11719-24, 1991 Dec 17.
[Is] ISSN:0006-2960
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Several bifunctional alkylating agents of the aziridinylbenzoquinone class have been evaluated as potential antitumor agents. 3,6-Bis[(2-hydroxyethyl)amino]-2,5- diaziridinyl-1,4-benzoquinone (BZQ), 2,5-diaziridinyl-1,4-benzoquinone (DZQ), 3,6-bis(carboxyamino)-2,5-diaziridinyl- 1,4-benzoquinone (AZQ), and six analogues of AZQ have been studied for their ability to induce DNA interstrand cross-linking, as measured by an agarose gel technique, and to determine whether they react with DNA in a sequence-selective manner, as determined by a modified DNA sequencing technique. At an equimolar concentration (10 microM), only DZQ and BZQ showed any detectable cross-linking at pH 7 without reduction. Cross-linking was enhanced in both cases at low pH (4). Reduction by ascorbic acid at both pH's increased the cross-linking, which was particularly striking in the case of DZQ. In contrast, AZQ and its analogues only produced a significant level of cross-linking under both low-pH and reducing conditions, the extent of cross-linking decreasing as the size of the alkyl end group increased. The compounds reacted with all guanine-N7 positions in DNA with a sequence selectivity similar to other chemotherapeutic alkylating agents, such as the nitrogen mustards, although some small differences were observed with BZQ. Nonreduced DZQ showed a qualitatively similar pattern of reactivity to the other compounds, but on reduction (at pH 4 or 7) was found to react almost exclusively with 5'-GC-3' sequences, and in particular, at 5'-TGC-3' sites. A model to explain this unique reaction is proposed.
[Mh] Termos MeSH primário: Aziridinas/farmacologia
Benzoquinonas/farmacologia
Reagentes para Ligações Cruzadas
DNA/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antineoplásicos
Autorradiografia
Aziridinas/química
Sequência de Bases
Benzoquinonas/química
Eletroforese em Gel de Ágar
Eletroforese em Gel de Poliacrilamida
Dados de Sequência Molecular
Oxirredução
Mostarda de Uracila/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Aziridines); 0 (Benzoquinones); 0 (Cross-Linking Reagents); 59886-54-3 (NSC 224070); 9007-49-2 (DNA); FQL5EUP13W (diaziquone); W7KQ46GJ8U (Uracil Mustard)
[Em] Mês de entrada:9201
[Cu] Atualização por classe:141120
[Lr] Data última revisão:
141120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:911217
[St] Status:MEDLINE


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[PMID]:2265064
[Au] Autor:O'Connor PM; Kohn KW
[Ad] Endereço:Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
[Ti] Título:Comparative pharmacokinetics of DNA lesion formation and removal following treatment of L1210 cells with nitrogen mustards.
[So] Source:Cancer Commun;2(12):387-94, 1990.
[Is] ISSN:0955-3541
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The kinetics of formation and removal of DNA interstrand crosslinks (ISC), DNA-protein crosslinks (DPC), and single strand breaks (SSB) by several nitrogen mustards were compared in order to determine the degree to which lesion selectivity may vary. The kinetic measurements using DNA alkaline elution methodology were obtained in mouse L1210 cells treated with mechlorethamine (HN2), phenylalanine mustard (L-PAM), uracil mustard (UM), 6-methyl-UM, and quinacrine mustard (QM). The ISC or DPC challenge delivered to cells was gauged on the basis of the kinetics as either total ISC or DPC produced, or as the area under the lesions versus time curve (AUC). By either measure (excepting QM), ISC correlated well with loss of colony survival, whereas DPC did not. The ISC/DPC ratio may therefore be a useful index of lesion selectivity. This ratio was significantly greater for 6-methyl-UM than for HN2. The ratio was also greater for L-PAM than for HN2 but only when gauged by AUC; this was attributable to an unusually slow rate for ISC removal in the case of L-PAM. The preferential reaction of UM at some 5'-GC-3' sites in purified DNA had suggested that UM might produce ISC with increased efficacy. UM, however, was somewhat less efficacious in ISC production than was 6-methyl-UM, which lacked selectivity for alkylation at 5'-GC-3'. QM was the only compound that produced detectable SSB, and the SSB were so numerous that ISC could not be quantitated.(ABSTRACT TRUNCATED AT 250 WORDS)
[Mh] Termos MeSH primário: Troca Genética
Dano ao DNA
Leucemia L1210/tratamento farmacológico
Compostos de Mostarda Nitrogenada/farmacologia
[Mh] Termos MeSH secundário: Animais
Ensaio de Unidades Formadoras de Colônias
Simulação por Computador
Técnicas In Vitro
Mecloretamina/farmacologia
Melfalan/farmacologia
Camundongos
Mostarda de Quinacrina/farmacologia
Mostarda de Uracila/análogos & derivados
Mostarda de Uracila/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nitrogen Mustard Compounds); 1LY7UH1WUT (chloroethylaminouracil); 4213-45-0 (Quinacrine Mustard); 50D9XSG0VR (Mechlorethamine); Q41OR9510P (Melphalan); W7KQ46GJ8U (Uracil Mustard)
[Em] Mês de entrada:9102
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:900101
[St] Status:MEDLINE



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