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[PMID]:28927522
[Au] Autor:Verma N; Tiku AB
[Ad] Endereço:Radiation and Cancer Therapeutics Lab, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
[Ti] Título:Significance and nature of bystander responses induced by various agents.
[So] Source:Mutat Res;773:104-121, 2017 Jul.
[Is] ISSN:1873-135X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Bystander effects in a biological system are the responses shown by non-targeted neighbouring cells/tissues/organisms. These responses are triggered by factors released from targeted cells when exposed to a stress inducing agent. The biological response to stress inducing agents is complex, owing to the diversity of mechanisms and pathways activated in directly targeted and bystander cells. These responses are highly variable and can be either beneficial or hazardous depending on the cell lines tested, dose of agent used, experimental end points and time course selected. Recently non-targeted cells have even been reported to rescue the directly exposed cells by releasing protective signals that might be induced by non-targeted bystander responses. The nature of bystander signal/s is not yet clear. However, there are evidences suggesting involvement of ROS, RNS, protein factors and even DNA molecules leading to the activation of a number of signaling pathways. These can act independently or in a cascade, to induce events leading to changes in gene expression patterns that could elicit detrimental or beneficial effects. Many review articles on radiation induced bystander responses have been published. However, to the best of our knowledge, a comprehensive review on bystander responses induced by other genotoxic chemicals and stress inducing agents has not been published so far. Therefore, the aim of the present review is to give an overview of the literature on different aspects of bystander responses: agents that induce these responses, factors that can modulate bystander responses and the mechanisms involved.
[Mh] Termos MeSH primário: Efeito Espectador/efeitos dos fármacos
Efeito Espectador/efeitos da radiação
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Técnicas de Cocultura
Dano ao DNA/efeitos dos fármacos
Dano ao DNA/efeitos da radiação
Seres Humanos
Metais Pesados/toxicidade
Nanopartículas/toxicidade
Compostos de Nitrosoureia/toxicidade
Radiação Ionizante
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Metals, Heavy); 0 (Nitrosourea Compounds)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170921
[St] Status:MEDLINE


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[PMID]:28143714
[Au] Autor:Nikolova T; Roos WP; Krämer OH; Strik HM; Kaina B
[Ad] Endereço:Institute of Toxicology, University Medical Center, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany. Electronic address: nikolova@uni-mainz.de.
[Ti] Título:Chloroethylating nitrosoureas in cancer therapy: DNA damage, repair and cell death signaling.
[So] Source:Biochim Biophys Acta;1868(1):29-39, 2017 08.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Chloroethylating nitrosoureas (CNU), such as lomustine, nimustine, semustine, carmustine and fotemustine are used for the treatment of malignant gliomas, brain metastases of different origin, melanomas and Hodgkin disease. They alkylate the DNA bases and give rise to the formation of monoadducts and subsequently interstrand crosslinks (ICL). ICL are critical cytotoxic DNA lesions that link the DNA strands covalently and block DNA replication and transcription. As a result, S phase progression is inhibited and cells are triggered to undergo apoptosis and necrosis, which both contribute to the effectiveness of CNU-based cancer therapy. However, tumor cells resist chemotherapy through the repair of CNU-induced DNA damage. The suicide enzyme O -methylguanine-DNA methyltransferase (MGMT) removes the precursor DNA lesion O -chloroethylguanine prior to its conversion into ICL. In cells lacking MGMT, the formed ICL evoke complex enzymatic networks to accomplish their removal. Here we discuss the mechanism of ICL repair as a survival strategy of healthy and cancer cells and DNA damage signaling as a mechanism contributing to CNU-induced cell death. We also discuss therapeutic implications and strategies based on sequential and simultaneous treatment with CNU and the methylating drug temozolomide.
[Mh] Termos MeSH primário: Morte Celular/efeitos dos fármacos
Dano ao DNA/efeitos dos fármacos
Reparo do DNA/efeitos dos fármacos
Neoplasias/tratamento farmacológico
Compostos de Nitrosoureia/farmacologia
Compostos de Nitrosoureia/uso terapêutico
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antineoplásicos Alquilantes/farmacologia
Antineoplásicos Alquilantes/uso terapêutico
Replicação do DNA/efeitos dos fármacos
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents, Alkylating); 0 (Nitrosourea Compounds)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170202
[St] Status:MEDLINE


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[PMID]:27994066
[Au] Autor:Chang S; Zhang P; Cairncross JG; Gilbert MR; Bahary JP; Dolinskas CA; Chakravarti A; Aldape KD; Bell EH; Schiff D; Jaeckle K; Brown PD; Barger GR; Werner-Wasik M; Shih H; Brachman D; Penas-Prado M; Robins HI; Belanger K; Schultz C; Hunter G; Mehta M
[Ad] Endereço:University of California San Francisco, San Francisco, California, USA.
[Ti] Título:Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813.
[So] Source:Neuro Oncol;19(2):252-258, 2017 02 01.
[Is] ISSN:1523-5866
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome. Methods: Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99). The study closed early because the target accrual rate was not met. Results: Median follow-up time for patients still alive was 10.1 years (1.9-12.6 y); 66% of the patients died. Median survival time was 3.9 years in the RT/TMZ arm (95% CI, 3.0-7.0) and 3.8 years in the RT/NU arm (95% CI, 2.2-7.0), corresponding to a hazard ratio (HR) of 0.94 (P = .36; 95% CI, 0.67-1.32). The differences in progression-free survival (PFS) and TTP between the 2 arms were not statistically significant. Patients in the RT+NU arm experienced more grade ≥3 toxicity (75.8% vs 47.9%, P < .001), mainly related to myelosuppression. Of the 196 patients, 111 were tested for IDH1-R132H status (60 RT+TMZ and 51 RT+NU). Fifty-four patients were IDH negative and 49 were IDH positive with a better OS in IDH-positive patients (median survival time 7.9 vs 2.8 y; P = .004, HR = 0.50; 95% CI, 0.31-0.81). Conclusions: RT+TMZ did not appear to significantly improve OS or TTP for AA compared with RT+ NU. RT+TMZ was better tolerated. IDH1-R132H mutation was associated with longer survival.
[Mh] Termos MeSH primário: Antineoplásicos Alquilantes/uso terapêutico
Astrocitoma/terapia
Neoplasias Encefálicas/terapia
Quimiorradioterapia
Dacarbazina/análogos & derivados
Compostos de Nitrosoureia/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Astrocitoma/metabolismo
Astrocitoma/patologia
Biomarcadores Tumorais/metabolismo
Neoplasias Encefálicas/metabolismo
Neoplasias Encefálicas/patologia
Dacarbazina/uso terapêutico
Feminino
Seguimentos
Seres Humanos
Masculino
Meia-Idade
Estadiamento de Neoplasias
Prognóstico
Estudos Prospectivos
Taxa de Sobrevida
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antineoplastic Agents, Alkylating); 0 (Biomarkers, Tumor); 0 (Nitrosourea Compounds); 7GR28W0FJI (Dacarbazine); YF1K15M17Y (temozolomide)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161221
[St] Status:MEDLINE
[do] DOI:10.1093/neuonc/now236


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[PMID]:27838504
[Au] Autor:Agarwal S; Tyagi G; Chadha D; Mehrotra R
[Ad] Endereço:Academy of Scientific & Innovative Research (AcSIR), CSIR-National Physical Laboratory Campus, New Delhi 110012, India; Quantum Phenomena and Applications, CSIR-National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi 110012, India.
[Ti] Título:Structural-conformational aspects of tRNA complexation with chloroethyl nitrosourea derivatives: A molecular modeling and spectroscopic investigation.
[So] Source:J Photochem Photobiol B;166:1-11, 2017 Jan.
[Is] ISSN:1873-2682
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Chloroethyl nitrosourea derivatives (CENUs) represent an important family of anticancer chemotherapeutic agents, which are used in the treatment of different types of cancer such as brain tumors, resistant or relapsed Hodgkin's disease, small cell lung cancer and malignant melanoma. This work focuses towards understanding the interaction of chloroethyl nitrosourea derivatives; lomustine, nimustine and semustine with tRNA using spectroscopic approach in order to elucidate their auxiliary anticancer action mechanism inside the cell. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), Fourier transform infrared difference spectroscopy, circular dichroism spectroscopy and UV-visible spectroscopy were employed to investigate the binding parameters of tRNA-CENUs complexation. Results of present study demonstrate that all CENUs, studied here, interact with tRNA through guanine nitrogenous base residues and possibly further crosslink cytosine residues in paired region of tRNA. Moreover, spectral data collected for nimustine-tRNA and semustine-tRNA complex formation indicates towards the groove-directed-alkylation as their anti-malignant action, which involves the participation of uracil moiety located in major groove of tRNA. Besides this, tRNA-CENUs adduct formation did not alter the native conformation of biopolymer and tRNA remains in A-form after its interaction with all three nitrosourea derivatives studied. The binding constants (K ) estimated for tRNA complexation with lomustine, nimustine and semustine are 2.55×10 M , 4.923×10 M and 4.223×10 M respectively, which specify weak type of CENU's binding with tRNA. Moreover, molecular modeling simulations were also performed to predict preferential binding orientation of CENUs with tRNA that corroborates well with spectral outcomes. The findings, presented here, recognize tRNA binding properties of CENUs that can further help in rational designing of more specific and efficient RNA targeted chemotherapeutic agents.
[Mh] Termos MeSH primário: Compostos de Nitrosoureia/química
Conformação de Ácido Nucleico
RNA de Transferência/química
[Mh] Termos MeSH secundário: Antineoplásicos/química
Dicroísmo Circular
Modelos Moleculares
Espectrofotometria Ultravioleta
Espectroscopia de Infravermelho com Transformada de Fourier
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Nitrosourea Compounds); 9014-25-9 (RNA, Transfer)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170411
[Lr] Data última revisão:
170411
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161114
[St] Status:MEDLINE


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[PMID]:27738081
[Au] Autor:Showler K; Nishimura M; Daino K; Imaoka T; Nishimura Y; Morioka T; Blyth BJ; Kokubo T; Takabatake M; Fukuda M; Moriyama H; Kakinuma S; Fukushi M; Shimada Y
[Ad] Endereço:Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo 116-8551, Japan.
[Ti] Título:Analysis of genes involved in the PI3K/Akt pathway in radiation- and MNU-induced rat mammary carcinomas.
[So] Source:J Radiat Res;58(2):183-194, 2017 Mar 01.
[Is] ISSN:1349-9157
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The PI3K/AKT pathway is one of the most important signaling networks in human breast cancer, and since it was potentially implicated in our preliminary investigations of radiation-induced rat mammary carcinomas, our aim here was to verify its role. We included mammary carcinomas induced by the chemical carcinogen 1-methyl-1-nitrosourea to determine whether any changes were radiation-specific. Most carcinomas from both groups showed activation of the PI3K/AKT pathway, but phosphorylation of AKT1 was often heterogeneous and only present in a minority of carcinoma cells. The negative pathway regulator Inpp4b was significantly downregulated in both groups, compared with in normal mammary tissue, and radiation-induced carcinomas also showed a significant decrease in Pten expression, while the chemically induced carcinomas showed a decrease in Pik3r1 and Pdk1. Significant upregulation of the positive regulators Erbb2 and Pik3ca was observed only in chemically induced carcinomas. However, no genes showed clear correlations with AKT phosphorylation levels, except in individual carcinomas. Only rare carcinomas showed mutations in PI3K/AKT pathway genes, yet these carcinomas did not exhibit stronger AKT phosphorylation. Thus, while AKT phosphorylation is a common feature of rat mammary carcinomas induced by radiation or a canonical chemical carcinogen, the mutation of key genes in the pathways or permanent changes to gene expression of particular signaling proteins do not explain the pathway activation in the advanced cancers. Although AKT signaling likely facilitates cancer development and growth in rat mammary carcinomas, it is unlikely that permanent disruption of the PI3K/AKT pathway genes is a major causal event in radiation carcinogenesis.
[Mh] Termos MeSH primário: Regulação Neoplásica da Expressão Gênica
Neoplasias Mamárias Experimentais/genética
Metilnitrosoureia/efeitos adversos
Compostos de Nitrosoureia/efeitos adversos
Fosfatidilinositol 3-Quinases/genética
Proteínas Proto-Oncogênicas c-akt/genética
Radiação Ionizante
Transdução de Sinais/genética
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Feminino
Regulação Neoplásica da Expressão Gênica/efeitos da radiação
Imuno-Histoquímica
Masculino
Neoplasias Mamárias Experimentais/patologia
Mutação de Sentido Incorreto/genética
Fosfatidilinositol 3-Quinases/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Ratos Sprague-Dawley
Deleção de Sequência/genética
Transdução de Sinais/efeitos da radiação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nitrosourea Compounds); 684-93-5 (Methylnitrosourea); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161015
[St] Status:MEDLINE
[do] DOI:10.1093/jrr/rrw097


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[PMID]:27453265
[Au] Autor:Ye S; Zheng X; Hu T; Zeng H
[Ad] Endereço:Peking University State Key Laboratory of Natural and Biomimetic Drugs Beijing China.
[Ti] Título:Synthesis, SAR and biological evaluation of a novel series of 1-(2-chloroethyl)-1-nitroso-3-(2-(3-oxobenzoelenazol-2(3H)-yl)ethyl) urea: Organoselenium compounds for cancer therapy.
[So] Source:Cell Mol Biol (Noisy-le-grand);62(7):6-14, 2016 Jun 30.
[Is] ISSN:1165-158X
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Thioredoxin reductase 1 (TrxR1) is an important potential anticancer drug target and closely related to both carcinogenesis and cancer progression. Ethaselen (BBSKE), a novel organoselenium compound inhibiting TrxR1 with selective antitumor effect, while its symmetrical structure results in poor solubility. Carmustine (BCNU), a DNA cross-link agent and also a deactivator of TrxR, is with high toxicity and low selectivity which limit its clinical application to some extents. Herein, a novel compound, 1-(2-chloroethyl)-1-nitroso-3-(2-(3-oxobenzoelenazol-2(3H)-yl)ethyl)urea(4a-1), which was designed through the combination of Ethaselen and Carmustine, showed good solubility, good tagetability, low toxicity and excellent antitumor activity by synergism. Using the structure of 4a-1 as a key active scaffold, a series of novel 1-(2-chloroethyl)-1-nitroso-3-(2-(3-oxobenzoelenazol-2(3H)-yl)ethyl)urea was designed, synthesized and evaluated to explore the structure-activity relationships (SARs) of these inhibitors and to improve their antitumor activities. Notably, 1-(2-chloroethyl)-3-(2-(6-fluoro-3-oxobenzoselenazol-2(3H)-yl)ethyl)-1-nitrosourea(4b-1) was found to exhibit more potent antitumor activities comparable to 4a-1 against all the four cancer cell lines, including Mia PaCa-2, PANC-1, RKO, LoVo. These results have highlighted compound 4b-1 as a new potential lead candidate for future development of novel potent broad-spectrum antitumor agents. In addition, a SAR model was established to conduct further structural modification.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Neoplasias/tratamento farmacológico
Compostos de Nitrosoureia/uso terapêutico
Compostos Organosselênicos/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Peso Corporal/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Seres Humanos
Ligantes
Simulação de Acoplamento Molecular
Neoplasias/patologia
Compostos de Nitrosoureia/síntese química
Compostos de Nitrosoureia/química
Compostos de Nitrosoureia/toxicidade
Compostos Organosselênicos/síntese química
Compostos Organosselênicos/química
Compostos Organosselênicos/toxicidade
Ratos
Solubilidade
Relação Estrutura-Atividade
Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores
Tiorredoxina Dissulfeto Redutase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-(2-chloroethyl)-3-(2-(5-fluoro-3-oxobenzoselenazol-2(3H)-yl)ethyl)-1-nitrosourea); 0 (Antineoplastic Agents); 0 (Ligands); 0 (Nitrosourea Compounds); 0 (Organoselenium Compounds); EC 1.8.1.9 (Thioredoxin-Disulfide Reductase)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170131
[Lr] Data última revisão:
170131
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160726
[St] Status:MEDLINE


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[PMID]:27365141
[Au] Autor:Sugimoto M; Ito S; Mashima K; Umino K; Minakata D; Nakano H; Yamasaki R; Kawasaki Y; Ashizawa M; Yamamoto C; Fujiwara S; Okazuka K; Hatano K; Sato K; Oh I; Ohmine K; Suzuki T; Muroi K; Kako S; Kanda Y
[Ad] Endereço:Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan.
[Ti] Título:Retrospective evaluation of the MEAM regimen as a conditioning regimen before autologous peripheral blood stem cell transplantation for lymphoma in two centers with different dosing schedules of melphalan.
[So] Source:Ann Hematol;95(9):1513-9, 2016 Sep.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The BEAM regimen consisting of carmustine (BCNU), etoposide, cytarabine, and melphalan (MEL) is widely used before autologous hematopoietic stem cell transplantation (auto-HSCT) for lymphoma. However, intravenous BCNU is not available in Japan, and therefore, ranimustine (MCNU) has been used instead of BCNU (the MEAM regimen). We retrospectively analyzed the outcome of 79 adult patients who underwent auto-HSCT for lymphoma using this regimen in two centers, with 1- and 2-day dosing of MEL, respectively. Three-year overall survival (OS) and progression-free survival (PFS) probabilities were 77.3 and 56.5 % in the entire population and 71.7 and 58.0 % in patients with diffuse large B cell lymphoma. These outcomes were at least equivalent to those with the BEAM regimen. There was no regimen-related pulmonary toxicity. In a multivariate analysis, older age was the only factor that was significantly associated with for OS. In a comparison of the two MEL dosing schedules, while there was no significant differences in either OS or PFS, diarrhea was observed more frequently with 1-day dosing of MEL. In conclusion, the MEAM regimen appeared to be a promising conditioning regimen in auto-HSCT for lymphoma. A large prospective study is warranted to confirm the current findings.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Linfoma/terapia
Transplante de Células-Tronco de Sangue Periférico/métodos
Condicionamento Pré-Transplante/métodos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Citarabina/administração & dosagem
Citarabina/efeitos adversos
Intervalo Livre de Doença
Relação Dose-Resposta a Droga
Etoposídeo/administração & dosagem
Etoposídeo/efeitos adversos
Neutropenia Febril/induzido quimicamente
Feminino
Seres Humanos
Linfoma/classificação
Masculino
Melfalan/administração & dosagem
Melfalan/efeitos adversos
Meia-Idade
Náusea/induzido quimicamente
Compostos de Nitrosoureia/administração & dosagem
Compostos de Nitrosoureia/efeitos adversos
Estudos Retrospectivos
Condicionamento Pré-Transplante/efeitos adversos
Transplante Autólogo
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Nitrosourea Compounds); 04079A1RDZ (Cytarabine); 6PLQ3CP4P3 (Etoposide); Q41OR9510P (Melphalan); RYH2T97J77 (ranimustine)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170202
[Lr] Data última revisão:
170202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160702
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-016-2740-9


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[PMID]:27352444
[Au] Autor:Kalogeraki A; Tamiolakis D; Mavrigiannaki P; Karvelaskalogerakis M; Datseri G; Agelaki S; Papadopoulos S
[Ti] Título:Recurrent Cerebellar Desmoplastic/Nodular Medulloblastoma in Cerebrospinal Fluid (CSF) in the Elderly. A Cytologic Diagnosis.
[So] Source:Rom J Intern Med;54(2):137-9, 2016 Apr-Jun.
[Is] ISSN:1220-4749
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Desmoplastic medulloblastoma is a rare subtype of medulloblastoma in childhood and more rare in adults. Cerebrospinal fluid (CSF) occurrence is frequent and important for treatment and prognosis. We report the CSF cytologic features of recurrent desmoplastic/nodular medulloblastoma in a 30-aged male.
[Mh] Termos MeSH primário: Neoplasias Cerebelares/líquido cefalorraquidiano
Neoplasias Cerebelares/diagnóstico
Líquido Cefalorraquidiano/citologia
Meduloblastoma/líquido cefalorraquidiano
Meduloblastoma/diagnóstico
Recidiva Local de Neoplasia/líquido cefalorraquidiano
Recidiva Local de Neoplasia/diagnóstico
[Mh] Termos MeSH secundário: Adulto
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias Cerebelares/tratamento farmacológico
Seres Humanos
Masculino
Meduloblastoma/tratamento farmacológico
Estadiamento de Neoplasias
Compostos de Nitrosoureia/uso terapêutico
Prognóstico
Doenças Raras
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nitrosourea Compounds)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:160629
[Lr] Data última revisão:
160629
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160629
[St] Status:MEDLINE


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[PMID]:27289375
[Au] Autor:Ogura M; Ishida T; Tsukasaki K; Takahashi T; Utsunomiya A
[Ad] Endereço:Department of Hematology, Tokai Central Hospital, Kakamigahara, Gifu, 504-8601, Japan. mi-ogura@naa.att.ne.jp.
[Ti] Título:Effects of first-line chemotherapy on natural killer cells in adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma.
[So] Source:Cancer Chemother Pharmacol;78(1):199-207, 2016 Jul.
[Is] ISSN:1432-0843
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Natural killer (NK) cells are well known to be the most important effector cells mediating antibody-dependent cellular cytotoxicity (ADCC) which is an important mechanism of action of antibody drugs. We evaluated the effects of chemotherapy on the cell number and activity of NK cells from patients who received the vincristine-cyclophosphamide-doxorubicin-prednisone (VCAP), doxorubicin-ranimustine-prednisone (AMP), and vindesine-etoposide-carboplatin-prednisone (VECP) (mLSG15) or mLSG15-like (-L) regimen, which is one of the standard of cares for newly diagnosed adult T-cell leukemia-lymphoma (ATL), or the cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) or CHOP-L regimen which is another standard of care for ATL and peripheral T-cell lymphoma (PTCL). METHODS: The number of lymphocytes and NK cells, and NK cell activity, were assessed using flow cytometry and a (51)Cr release assay, respectively. RESULTS: A total of 26 patients with untreated ATL or PTCL were enrolled, and blood samples from 25 patients were evaluable. NK cell number in ATL decreased after mLSG15/-L treatment, and the degree of decrease in the NK cell number was more prominent just before VECP therapy (Day 15-17 of each cycle) than just before VCAP therapy (Day 1 of each cycle). The NK cell number in ATL after CHOP/-L treatment also decreased. Interestingly, the NK cell activity showed a tendency to increase after the treatment. NK cell number in PTCL did not decrease by CHOP/-L regimen, but the activity was slightly decreased after the treatment. CONCLUSIONS: These results indicate that the effects of chemotherapeutic agents on NK cells vary according to the disease type and intensity of chemotherapy.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Células Matadoras Naturais/efeitos dos fármacos
Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico
Linfoma de Células T Periférico/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Carboplatina/administração & dosagem
Estudos de Casos e Controles
Ciclofosfamida/administração & dosagem
Ciclofosfamida/farmacologia
Ciclofosfamida/uso terapêutico
Doxorrubicina/administração & dosagem
Doxorrubicina/farmacologia
Doxorrubicina/uso terapêutico
Etoposídeo/administração & dosagem
Feminino
Citometria de Fluxo
Seres Humanos
Células Matadoras Naturais/metabolismo
Leucemia-Linfoma de Células T do Adulto/patologia
Linfoma de Células T Periférico/patologia
Masculino
Meia-Idade
Compostos de Nitrosoureia/administração & dosagem
Prednisona/administração & dosagem
Prednisona/farmacologia
Prednisona/uso terapêutico
Vincristina/administração & dosagem
Vincristina/farmacologia
Vincristina/uso terapêutico
Vindesina/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Nitrosourea Compounds); 5J49Q6B70F (Vincristine); 6PLQ3CP4P3 (Etoposide); 80168379AG (Doxorubicin); 8N3DW7272P (Cyclophosphamide); BG3F62OND5 (Carboplatin); RSA8KO39WH (Vindesine); RYH2T97J77 (ranimustine); VB0R961HZT (Prednisone)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160613
[St] Status:MEDLINE
[do] DOI:10.1007/s00280-016-3070-2


  10 / 3729 MEDLINE  
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[PMID]:27041398
[Au] Autor:Sun G; Zhang N; Zhao L; Fan T; Zhang S; Zhong R
[Ad] Endereço:Beijing Key Laboratory of Environmental & Viral Oncology, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, PR China.
[Ti] Título:Synthesis and antitumor activity evaluation of a novel combi-nitrosourea prodrug: Designed to release a DNA cross-linking agent and an inhibitor of O(6)-alkylguanine-DNA alkyltransferase.
[So] Source:Bioorg Med Chem;24(9):2097-107, 2016 May 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The drug resistance of CENUs induced by O(6)-alkylguanine-DNA alkyltransferase (AGT), which repairs the O(6)-alkylated guanine and subsequently inhibits the formation of dG-dC cross-links, hinders the application of CENU chemotherapies. Therefore, the discovery of CENU analogs with AGT inhibiting activity is a promising approach leading to novel CENU chemotherapies with high therapeutic index. In this study, a new combi-nitrosourea prodrug 3-(3-(((2-amino-9H-purin-6-yl)oxy)methyl)benzyl)-1-(2-chloroethyl)-1-nitrosourea (6), designed to release a DNA cross-linking agent and an inhibitor of AGT, was synthesized and evaluated for its antitumor activity and ability to induce DNA interstrand cross-links (ICLs). The results indicated that 6 exhibited higher cytotoxicity against mer(+) glioma cells compared with ACNU, BCNU, and their respective combinations with O(6)-benzylguanine (O(6)-BG). Quantifications of dG-dC cross-links induced by 6 were performed using HPLC-ESI-MS/MS. Higher levels of dG-dC cross-link were observed in 6-treated human glioma SF763 cells (mer(+)), whereas lower levels of dG-dC cross-link were observed in 6-treated calf thymus DNA, when compared with the groups treated with BCNU and ACNU. The results suggested that the superiority of 6 might result from the AGT inhibitory moiety, which specifically functions in cells with AGT activity. Molecular docking studies indicated that five hydrogen bonds were formed between the O(6)-BG analogs released from 6 and the five residues in the active pocket of AGT, which provided a reasonable explanation for the higher AGT-inhibitory activity of 6 than O(6)-BG.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Reagentes para Ligações Cruzadas/química
Inibidores Enzimáticos/farmacologia
Compostos de Nitrosoureia/farmacologia
O(6)-Metilguanina-DNA Metiltransferase/antagonistas & inibidores
Pró-Fármacos/farmacologia
[Mh] Termos MeSH secundário: Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cross-Linking Reagents); 0 (Enzyme Inhibitors); 0 (Nitrosourea Compounds); 0 (Prodrugs); EC 2.1.1.63 (O(6)-Methylguanine-DNA Methyltransferase)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160405
[St] Status:MEDLINE



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