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[PMID]:29269697
[Au] Autor:Himeno T; Shiga Y; Takeshima S; Tachiyama K; Kamimura T; Kono R; Takemaru M; Takeshita J; Shimoe Y; Kuriyama M
[Ad] Endereço:Department of Neurology, Brain Attack Center, Ota Memorial Hospital.
[Ti] Título:[Clinical, epidemiological, and etiological studies of adult aseptic meningitis: a report of 12 cases of herpes simplex meningitis, and a comparison with cases of herpes simplex encephalitis].
[So] Source:Rinsho Shinkeigaku;58(1):1-8, 2018 Jan 26.
[Is] ISSN:1882-0654
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:We treated 437 cases of adult aseptic meningitis and 12 cases (including 2 recurrent patients; age, 31.8 ± 8.9 years; 7 females) of herpes simplex meningitis from 2004 to 2016. The incidence rate of adult herpes simplex meningitis in the cases with aseptic meningitis was 2.7%. One patient was admitted during treatment of genital herpes, but no association was observed between genital herpes and herpes simplex meningitis in the other cases. The diagnoses were confirmed in all cases as the cerebrospinal fluid (CSF) was positive for herpes simplex virus (HSV)-DNA. For diagnosis confirmation, the DNA test was useful after 2-7 days following initial disease onset. Among other types of aseptic meningitis, the patients with herpes simplex meningitis showed relatively high white blood cell counts and relatively high CSF protein and high CSF cell counts. CSF cells showed mononuclear cell dominance from the initial stage of the disease. During same period, we also experienced 12 cases of herpes simplex encephalitis and 21 cases of non-hepatic acute limbic encephalitis. Notably, the patients with herpes simplex meningitis were younger and their CSF protein and cells counts were higher than those of the patients with herpes simplex encephalitis.
[Mh] Termos MeSH primário: Encefalite por Herpes Simples
Herpes Simples
Meningite Viral
[Mh] Termos MeSH secundário: Adolescente
Adulto
Fatores Etários
Biomarcadores/líquido cefalorraquidiano
Contagem de Células
Líquido Cefalorraquidiano/citologia
Proteínas do Líquido Cefalorraquidiano/líquido cefalorraquidiano
DNA Viral/líquido cefalorraquidiano
Encefalite por Herpes Simples/líquido cefalorraquidiano
Encefalite por Herpes Simples/diagnóstico
Encefalite por Herpes Simples/epidemiologia
Encefalite por Herpes Simples/virologia
Feminino
Seres Humanos
Masculino
Meningite Viral/líquido cefalorraquidiano
Meningite Viral/diagnóstico
Meningite Viral/epidemiologia
Meningite Viral/virologia
Meia-Idade
Simplexvirus/genética
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cerebrospinal Fluid Proteins); 0 (DNA, Viral)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171223
[St] Status:MEDLINE
[do] DOI:10.5692/clinicalneurol.cn-001098


  2 / 16444 MEDLINE  
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[PMID]:28454912
[Au] Autor:Pertusati F; Serafini S; Albadry N; Snoeck R; Andrei G
[Ad] Endereço:School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, CF10 3NB, Cardiff, Wales, United Kingdom. Electronic address: pertusatif1@cardiff.ac.uk.
[Ti] Título:Phosphonoamidate prodrugs of C5-substituted pyrimidine acyclic nucleosides for antiviral therapy.
[So] Source:Antiviral Res;143:262-268, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Acyclic nucleoside phosphonates (ANPs) are nowadays one of the key drugs in the treatment of DNA virus and retrovirus infections. In this work, we report the synthesis and antiviral evaluation of phosphonoamidate and diamidates prodrugs of C5-pyrimidine acyclic nucleosides derivatives functionalized with but-2-enyl- chain. In the phosphonoamidate series, the most active compound 15, showed sub-micromolar activity against varicella zoster virus (VZV) (EC = 0.09-0.5 µM) and µM activity against human cytomegalovirus (HCMV) and herpes simplex virus (HSV). Separation of single diastereoisomers for compound 14, showed that 14b had better anti-herpesvirus activity and no cytotoxicity compared to the diastereoisomeric mixture 14. Very interestingly, phosphonodiamidate 21 showed anti-herpesvirus activity with excellent activity against wild type and thymidine kinase-deficient (TK ) VZV strains (EC = 0.47 and 0.2 µM, respectively) and HCMV (EC = 3.5-7.2 µM) without any cytotoxicity (CC > 100).
[Mh] Termos MeSH primário: Pró-Fármacos/síntese química
Pró-Fármacos/farmacologia
Nucleosídeos de Pirimidina/síntese química
Nucleosídeos de Pirimidina/farmacologia
[Mh] Termos MeSH secundário: Antivirais/síntese química
Antivirais/farmacologia
Linhagem Celular
Citomegalovirus/efeitos dos fármacos
Herpesvirus Humano 3/efeitos dos fármacos
Seres Humanos
Simplexvirus/efeitos dos fármacos
Timidina Quinase
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Prodrugs); 0 (Pyrimidine Nucleosides); EC 2.7.1.21 (Thymidine Kinase)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


  3 / 16444 MEDLINE  
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[PMID]:28470128
[Au] Autor:Parsons BF; Ryder N
[Ad] Endereço:1 Pacific Clinic Newcastle, HNE Sexual Health, Newcastle, NSW, Australia.
[Ti] Título:Pseudoepitheliomatous hyperplasia causing a painful plaque in a HIV-infected female.
[So] Source:Int J STD AIDS;28(7):723-725, 2017 06.
[Is] ISSN:1758-1052
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Dermatological conditions are more common and can present atypically, in human immunodeficiency virus-infected individuals. This case report describes a 22-year-old human immunodeficiency virus-positive Caucasian female who presented with a vulval lesion eight weeks after starting antiretroviral treatment. Clinical examination revealed a 2 cm well-demarcated plaque on the outer aspect of the left labium minus. The lesion was tender, no contact bleeding or ulceration present. She was presumptively treated for chancroid and herpes simplex with 500 mg ceftriaxone IM stat, 1 g azithromycin PO stat, and valacyclovir 500 mg BD for five days. The lesion persisted despite treatment, and during follow-up, a punch biopsy was carried out. She was diagnosed with pseudoepitheliomatous hyperplasia of the epidermis. In addition to highlighting this condition that has been previously reported in human immunodeficiency virus/herpes simplex virus co-infection, this case demonstrates that unusual skin presentations must be considered in human immunodeficiency virus-infected individuals and illustrates the importance of biopsy for any non-healing lesions.
[Mh] Termos MeSH primário: Infecções por HIV/complicações
Herpes Genital/diagnóstico
Hiperplasia/patologia
Vulva/patologia
Doenças da Vulva/diagnóstico
[Mh] Termos MeSH secundário: Adulto
Fármacos Anti-HIV/uso terapêutico
Biópsia
Coinfecção/virologia
Feminino
Infecções por HIV/tratamento farmacológico
Herpes Genital/complicações
Herpes Genital/tratamento farmacológico
Herpes Genital/microbiologia
Seres Humanos
Hospedeiro Imunocomprometido
Simplexvirus
Resultado do Tratamento
Doenças da Vulva/complicações
Doenças da Vulva/tratamento farmacológico
Doenças da Vulva/microbiologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM; X
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1177/0956462416676020


  4 / 16444 MEDLINE  
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[PMID]:28466551
[Au] Autor:Nilsson J; Granrot I; Mattsson J; Omazic B; Uhlin M; Thunberg S
[Ad] Endereço:Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
[Ti] Título:Functionality testing of stem cell grafts to predict infectious complications after allogeneic hematopoietic stem cell transplantation.
[So] Source:Vox Sang;112(5):459-468, 2017 Jul.
[Is] ISSN:1423-0410
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND OBJECTIVES: Allogeneic hematopoietic stem cell transplantation (HSCT) is a routine clinical procedure performed to treat patients with haematological malignancies, primary immune deficiencies or metabolic disorders. Infections during lymphopenia after allogeneic HSCT are associated with high mortality and morbidity. Typical infectious agents are Epstein-Barr virus, cytomegalovirus, herpes simplex virus, varicella-zoster virus and fungi. The study aim was to evaluate whether measurement of the responses of antigen-specific T-cells, recognizing infectious pathogens would correlate to protective functions in the stem cell recipient post-transplant. MATERIALS AND METHODS: Twenty-one grafts were analysed by flow cytometry and cells were stimulated in vitro with relevant infectious antigens, followed by evaluation of T-cell proliferation and cytokine production. Results were compared to the recipients' clinical records 1-year post-transplantation. RESULTS: We show that an extensive repertoire of transferred antigen-specific T-cells from allogeneic donor grafts against infectious agents, involved in post-transplant infections, are linked to an absence of infectious complications for the recipient up-to 1-year post-transplant. The protective effect was associated with antigen-specific T-cell proliferation and IL-1ß secretion. CONCLUSION: Our results suggest that assaying T-cell function before HSCT could determine individual risks for infectious complications and thus aid in clinical decision-making regarding prophylactic and pre-emptive anti-infective therapy.
[Mh] Termos MeSH primário: Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Células-Tronco Hematopoéticas/fisiologia
Viroses/prevenção & controle
[Mh] Termos MeSH secundário: Adenoviridae/imunologia
Adolescente
Adulto
Idoso
Candida/imunologia
Criança
Pré-Escolar
Citomegalovirus/imunologia
Feminino
Citometria de Fluxo
Neoplasias Hematológicas/terapia
Herpesvirus Humano 3/imunologia
Herpesvirus Humano 4/imunologia
Seres Humanos
Lactente
Controle de Infecções/métodos
Contagem de Leucócitos
Ativação Linfocitária
Masculino
Meia-Idade
Simplexvirus/imunologia
Linfócitos T/imunologia
Linfócitos T/virologia
Transplante Homólogo/efeitos adversos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1111/vox.12521


  5 / 16444 MEDLINE  
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[PMID]:28468883
[Au] Autor:Srivastava R; Khan AA; Chilukuri S; Syed SA; Tran TT; Furness J; Bahraoui E; BenMohamed L
[Ad] Endereço:Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, USA.
[Ti] Título:CXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8 T and CD8 T Cells within Infected Tissues Allows Efficient Protection against Recurrent Herpesvirus Infection and Disease.
[So] Source:J Virol;91(14), 2017 Jul 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Herpes simplex virus 1 (HSV-1) establishes latency within the sensory neurons of the trigeminal ganglia (TG). HSV-specific memory CD8 T cells play a critical role in preventing HSV-1 reactivation from TG and subsequent virus shedding in tears that trigger recurrent corneal herpetic disease. The CXC chemokine ligand 10 (CXCL10)/CXC chemokine receptor 3 (CXCR3) chemokine pathway promotes T cell immunity to many viral pathogens, but its importance in CD8 T cell immunity to recurrent herpes has been poorly elucidated. In this study, we determined how the CXCL10/CXCR3 pathway affects TG- and cornea-resident CD8 T cell responses to recurrent ocular herpesvirus infection and disease using a well-established murine model in which HSV-1 reactivation was induced from latently infected TG by UV-B light. Following UV-B-induced HSV-1 reactivation, a significant increase in both the number and function of HSV-specific CXCR3 CD8 T cells was detected in TG and corneas of protected C57BL/6 (B6) mice, but not in TG and corneas of nonprotected CXCL10 or CXCR3 deficient mice. This increase was associated with a significant reduction in both virus shedding and recurrent corneal herpetic disease. Furthermore, delivery of exogenous CXCL10 chemokine in TG of CXCL10 mice, using the neurotropic adeno-associated virus type 8 (AAV8) vector, boosted the number and function of effector memory CD8 T cells (T ) and tissue-resident memory CD8 T cells (T ), but not of central memory CD8 T cells (T ), locally within TG, and improved protection against recurrent herpesvirus infection and disease in CXCL10 deficient mice. These findings demonstrate that the CXCL10/CXCR3 chemokine pathway is critical in shaping CD8 T cell immunity, locally within latently infected tissues, which protects against recurrent herpesvirus infection and disease. We determined how the CXCL10/CXCR3 pathway affects CD8 T cell responses to recurrent ocular herpesvirus infection and disease. Using a well-established murine model, in which HSV-1 reactivation in latently infected trigeminal ganglia was induced by UV-B light, we demonstrated that lack of either CXCL10 chemokine or its CXCR3 receptor compromised the mobilization of functional CD8 T and CD8 T cells within latently infected trigeminal ganglia following virus reactivation. This lack of T cell mobilization was associated with an increase in recurrent ocular herpesvirus infection and disease. Inversely, augmenting the amount of CXCL10 in trigeminal ganglia of latently infected CXCL10-deficient mice significantly restored the number of local antiviral CD8 T and CD8 T cells associated with protection against recurrent ocular herpes. Based on these findings, a novel "prime/pull" therapeutic ocular herpes vaccine strategy is proposed and discussed.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Quimiocina CXCL10/metabolismo
Herpes Simples/imunologia
Memória Imunológica
Receptores CXCR3/metabolismo
Simplexvirus/imunologia
[Mh] Termos MeSH secundário: Animais
Quimiocina CXCL10/deficiência
Córnea/imunologia
Córnea/virologia
Modelos Animais de Doenças
Herpes Simples/prevenção & controle
Camundongos Endogâmicos C57BL
Camundongos Knockout
Receptores CXCR3/deficiência
Recidiva
Gânglio Trigeminal/imunologia
Gânglio Trigeminal/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chemokine CXCL10); 0 (Cxcl10 protein, mouse); 0 (Cxcr3 protein, mouse); 0 (Receptors, CXCR3)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE


  6 / 16444 MEDLINE  
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[PMID]:28451758
[Au] Autor:Qiu J; Huang F; Wang Z; Xu J; Zhang C
[Ad] Endereço:Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.
[Ti] Título:The evaluation of diagnostic efficiency for stromal herpes simplex keratitis by the combination of tear HSV-sIgA and HSV-DNA.
[So] Source:Graefes Arch Clin Exp Ophthalmol;255(7):1409-1415, 2017 Jul.
[Is] ISSN:1435-702X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To assess the differential diagnostic values for stromal herpes simplex keratitis (HSK) by using tear HSV-sIgA, tear HSV-DNA, and the combination. METHODS: Tear samples for both eyes and the paired serum were collected from 187 stromal HSK and 56 controls. Enzyme-linked immune sorbent assay (ELISA) was used to analyze the tear HSV-sIgA and serum IgG/IgM/IgA. The levels of tear HSV-DNA were measured by polymerase chain reaction (PCR). RESULTS: The positive rates for tear HSV-sIgA and HSV-DNA were 36.90% and 10.96% respectively in stromal HSK patients. Twelve showed positivity for both sIgA and DNA, while 46 cases were positive for sIgA or DNA. The sensitivity, specificity, PPV, and NPV for simultaneous measurement were 39.73%, 98.21%, 98.31%, and 38.46%. The total negative conversion rate of sIgA was 95.71%. CONCLUSIONS: The diagnostic efficiency of HSV-sIgA only is nearly equal to the combination of HSV-sIgA and HSV-DNA, and the positive result is optimum to achieve a reliable diagnosis of stromal HSK even in atypical or unsuspected cases.
[Mh] Termos MeSH primário: Substância Própria/patologia
DNA Viral/análise
Infecções Oculares Virais/diagnóstico
Imunoglobulina A Secretora/metabolismo
Ceratite Herpética/diagnóstico
Simplexvirus/genética
Lágrimas/virologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Criança
Pré-Escolar
Substância Própria/diagnóstico por imagem
Substância Própria/virologia
Ensaio de Imunoadsorção Enzimática
Infecções Oculares Virais/metabolismo
Infecções Oculares Virais/virologia
Feminino
Seres Humanos
Lactente
Recém-Nascido
Ceratite Herpética/metabolismo
Ceratite Herpética/virologia
Masculino
Meia-Idade
Reação em Cadeia da Polimerase
Reprodutibilidade dos Testes
Estudos Retrospectivos
Lágrimas/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Viral); 0 (Immunoglobulin A, Secretory)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1007/s00417-017-3653-6


  7 / 16444 MEDLINE  
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[PMID]:28829913
[Au] Autor:Derudas M; Vanpouille C; Carta D; Zicari S; Andrei G; Snoeck R; Brancale A; Margolis L; Balzarini J; McGuigan C
[Ad] Endereço:Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University , Cardiff, CF10 3NB, U.K.
[Ti] Título:Virtual Screening of Acyclovir Derivatives as Potential Antiviral Agents: Design, Synthesis, and Biological Evaluation of New Acyclic Nucleoside ProTides.
[So] Source:J Med Chem;60(18):7876-7896, 2017 Sep 28.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Following our findings on the anti-human immunodeficiency virus (HIV) activity of acyclovir (ACV) phosphate prodrugs, we herein report the ProTide approach applied to a series of acyclic nucleosides aimed at the identification of novel and selective antiviral, in particular anti-HIV agents. Acyclic nucleoside analogues used in this study were identified through a virtual screening using HIV-reverse transcriptase (RT), adenylate/guanylate kinase, and human DNA polymerase γ. A total of 39 new phosphate prodrugs were synthesized and evaluated against HIV-1 (in vitro and ex vivo human tonsillar tissue system) and human herpes viruses. Several ProTide compounds showed substantial potency against HIV-1 at low micromolar range while the parent nucleosides were not effective. Also, pronounced inhibition of herpesvirus replication was observed. A carboxypeptidase-mediated hydrolysis study was performed for a selection of compounds to assess the formation of putative metabolites and support the biological activity observed.
[Mh] Termos MeSH primário: Aciclovir/análogos & derivados
Aciclovir/farmacologia
Fármacos Anti-HIV/química
Fármacos Anti-HIV/farmacologia
HIV-1/efeitos dos fármacos
Nucleosídeos/química
Nucleosídeos/farmacologia
[Mh] Termos MeSH secundário: Linhagem Celular
Desenho de Drogas
Infecções por HIV/tratamento farmacológico
Infecções por HIV/virologia
Transcriptase Reversa do HIV/metabolismo
HIV-1/enzimologia
Herpes Simples/tratamento farmacológico
Herpes Simples/virologia
Seres Humanos
Simulação de Acoplamento Molecular
Simplexvirus/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Nucleosides); EC 2.7.7.49 (HIV Reverse Transcriptase); X4HES1O11F (Acyclovir)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b01009


  8 / 16444 MEDLINE  
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[PMID]:28801914
[Au] Autor:Esaki S; Nigim F; Moon E; Luk S; Kiyokawa J; Curry W; Cahill DP; Chi AS; Iafrate AJ; Martuza RL; Rabkin SD; Wakimoto H
[Ad] Endereço:Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
[Ti] Título:Blockade of transforming growth factor-ß signaling enhances oncolytic herpes simplex virus efficacy in patient-derived recurrent glioblastoma models.
[So] Source:Int J Cancer;141(11):2348-2358, 2017 Dec 01.
[Is] ISSN:1097-0215
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Transforming growth factor beta (TGF-ß) plays vital roles in maintaining GSC stemness and GBM pathogenesis. We hypothesized that oHSV and TGF-ß inhibitors would synergistically exert antitumor effects for recurrent GBM. Here we established a panel of patient-derived recurrent tumor models from GBMs that relapsed after postsurgical radiation and chemotherapy, based on GSC-enriched tumor sphere cultures. These GSCs are resistant to the standard-of-care temozolomide but susceptible to oHSVs G47Δ and MG18L. Inhibition of TGF-ß receptor kinase with selective targeted small molecules reduced clonogenic sphere formation in all tested recurrent GSCs. The combination of oHSV and TGF-ßR inhibitor was synergistic in killing recurrent GSCs through, in part, an inhibitor-induced JNK-MAPK blockade and increase in oHSV replication. In vivo, systemic treatment with TGF-ßR inhibitor greatly enhanced the antitumor effects of single intratumoral oHSV injections, resulting in cures in 60% of mice bearing orthotopic recurrent GBM. These results reveal a novel synergistic interaction of oHSV therapy and TGF-ß signaling blockade, and warrant further investigations aimed at clinical translation of this combination strategy for GBM patients.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Neoplasias Encefálicas/patologia
Glioblastoma/patologia
Terapia Viral Oncolítica/métodos
Fator de Crescimento Transformador beta/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Western Blotting
Seres Humanos
Imuno-Histoquímica
Camundongos
Camundongos SCID
Células-Tronco Neoplásicas/efeitos dos fármacos
Células-Tronco Neoplásicas/patologia
Reação em Cadeia da Polimerase em Tempo Real
Transdução de Sinais/efeitos dos fármacos
Simplexvirus
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Transforming Growth Factor beta)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170813
[St] Status:MEDLINE
[do] DOI:10.1002/ijc.30929


  9 / 16444 MEDLINE  
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[PMID]:28757102
[Au] Autor:Krecmerová M; Dracínský M; Snoeck R; Balzarini J; Pomeisl K; Andrei G
[Ad] Endereço:Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nám. 2, CZ-166 10, Prague 6, Czech Republic. Electronic address: marcela@uochb.cas.cz.
[Ti] Título:New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity.
[So] Source:Bioorg Med Chem;25(17):4637-4648, 2017 Sep 01.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:New 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]pyrimidine (PMEO-DAPy) and 1-[2-(phosphonomethoxy)ethyl]-5-azacytosine (PME-5-azaC) prodrugs were prepared with a pro-moiety consisting of carbonyloxymethyl esters (POM, POC), alkoxyalkyl esters, amino acid phosphoramidates and/or tyrosine. The activity of the prodrugs was evaluated in vitro against different virus families. None of the synthesized prodrugs demonstrated activity against RNA viruses but some of them proved active against herpesviruses [including herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV)]. The bis(POC) and the bis(amino acid) phosphoramidate prodrugs of PMEO-DAPy inhibited herpesvirus replication at lower doses than the parent compound although the selectivity against HSV and VZV was only slightly improved compared to PMEO-DAPy. The mono-octadecyl ester of PME-5-azaC emerged as the most potent and selective PME-5-azaC prodrug against HSV, VZV and HCMV with EC 's of 0.15-1.12µM while PME-5-azaC only had marginal anti-herpesvirus activity. Although the bis(hexadecylamido-l-tyrosyl) and the bis(POM) esters of PME-5-azaC were also very potent anti-herpesvirus drugs, these were less selective than the mono-octadecyl ester prodrug.
[Mh] Termos MeSH primário: Antivirais/síntese química
Organofosfonatos/química
Pró-Fármacos/síntese química
Nucleosídeos de Pirimidina/química
[Mh] Termos MeSH secundário: Antivirais/química
Antivirais/farmacologia
Linhagem Celular
Citomegalovirus/efeitos dos fármacos
Herpesvirus Humano 3/efeitos dos fármacos
Seres Humanos
Organofosfonatos/síntese química
Organofosfonatos/farmacologia
Pró-Fármacos/química
Pró-Fármacos/farmacologia
Simplexvirus/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Organophosphonates); 0 (Prodrugs); 0 (Pyrimidine Nucleosides)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE


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[PMID]:28723548
[Au] Autor:Dai HS; Griffin N; Bolyard C; Mao HC; Zhang J; Cripe TP; Suenaga T; Arase H; Nakano I; Chiocca EA; Kaur B; Yu J; Caligiuri MA
[Ad] Endereço:The Ohio State University Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA; Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205, USA. Electronic address: daihsh@gmail.
[Ti] Título:The Fc Domain of Immunoglobulin Is Sufficient to Bridge NK Cells with Virally Infected Cells.
[So] Source:Immunity;47(1):159-170.e10, 2017 Jul 18.
[Is] ISSN:1097-4180
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Clearance of pathogens or tumor cells by antibodies traditionally requires both Fab and Fc domains of IgG. Here, we show the Fc domain of IgG alone mediates recognition and clearance of herpes simplex virus (HSV1)-infected cells. The human natural killer (NK) cell surface is naturally coated with IgG bound by its Fc domain to the Fcγ receptor CD16a. NK cells utilize the Fc domain of bound IgG to recognize gE, an HSV1-encoded glycoprotein that also binds the Fc domain of IgG but at a site distinct from CD16a. The bridge formed by the Fc domain between the HSV1-infected cell and the NK cell results in NK cell activation and lysis of the HSV1-infected cell in the absence of HSV1-specific antibody in vitro and prevents fatal HSV1 infection in vivo. This mechanism also explains how bacterial IgG-binding proteins regulate NK cell function and may be broadly applicable to Fcγ-receptor-bearing cells.
[Mh] Termos MeSH primário: Anticorpos Antivirais/metabolismo
Herpes Simples/imunologia
Fragmentos Fc das Imunoglobulinas/metabolismo
Imunoglobulina G/metabolismo
Células Matadoras Naturais/imunologia
Simplexvirus/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais/imunologia
Células Cultivadas
Citotoxicidade Imunológica
Feminino
Seres Humanos
Fragmentos Fc das Imunoglobulinas/imunologia
Imunoglobulina G/imunologia
Ativação Linfocitária
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Ligação Proteica
Agregação de Receptores
Receptores de IgG/metabolismo
Transdução de Sinais
Proteínas Virais/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Immunoglobulin Fc Fragments); 0 (Immunoglobulin G); 0 (Receptors, IgG); 0 (Viral Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE



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