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  1 / 37711 MEDLINE  
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[PMID]:28456791
[Au] Autor:Dondero A; Casu B; Bellora F; Vacca A; De Luisi A; Frassanito MA; Cantoni C; Gaggero S; Olive D; Moretta A; Bottino C; Castriconi R
[Ad] Endereço:Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy.
[Ti] Título:NK cells and multiple myeloma-associated endothelial cells: molecular interactions and influence of IL-27.
[So] Source:Oncotarget;8(21):35088-35102, 2017 May 23.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Angiogenesis represents a hallmark of tumor progression in Multiple Myeloma (MM), a still incurable malignancy. Here we analyzed the activity of cytokine-stimulated NK cells against tumor-associated endothelial cells isolated from bone marrow aspirates of MM patients with active disease (MMECs). We show that NK cells activated with optimal doses of IL-15 killed MMECs thanks to the concerted action of multiple activating receptors. In particular, according to the high expression of PVR and Nectin-2 on MMECs, DNAM-1 actively participated in target recognition. Interestingly, in MMECs the surface density of PVR was significantly higher than that detected in endothelium from patients with MM in complete remission or with monoclonal gammopathy of undetermined significance (MGUS). Importantly, IL-27, which unlike IL-15 does not display pro-angiogenic properties, maintained or increased the NK cell functions induced by suboptimal concentrations of IL-15. NK cell properties included killing of MMECs, IFN-γ production as well as a peculiar increase of NKp46 expression on NK cell surface. Finally, IL-27 showed a striking capability of up-regulating the expression of PD-L2 and HLA-I on tumor endothelium, whereas it did not modify that of PD-L1 and HLA-II.Our results suggest that cytokine-activated endogenous or adoptively transferred NK cells might support conventional therapies improving the outcome of MM patients.
[Mh] Termos MeSH primário: Células Endoteliais/efeitos dos fármacos
Interleucinas/metabolismo
Células Matadoras Naturais/efeitos dos fármacos
Mieloma Múltiplo/imunologia
[Mh] Termos MeSH secundário: Idoso
Células Endoteliais/citologia
Células Endoteliais/metabolismo
Feminino
Seres Humanos
Interleucina-15/farmacologia
Células Matadoras Naturais/citologia
Células Matadoras Naturais/metabolismo
Masculino
Meia-Idade
Mieloma Múltiplo/metabolismo
Neovascularização Patológica
Receptores Virais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IL27 protein, human); 0 (Interleukin-15); 0 (Interleukins); 0 (Receptors, Virus); 0 (poliovirus receptor)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.17070


  2 / 37711 MEDLINE  
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[PMID]:29267667
[Au] Autor:Silva LABD; Sá MAR; Melo RA; Pereira JDS; Silveira ÉJDD; Miguel MCDC
[Ad] Endereço:Universidade Federal do Rio Grande do Norte - UFRN, Postgraduate Program in Oral Pathology, Natal, RN, Brazil.
[Ti] Título:Analysis of CD57+ natural killer cells and CD8+ T lymphocytes in periapical granulomas and radicular cysts.
[So] Source:Braz Oral Res;31:e106, 2017 Dec 18.
[Is] ISSN:1807-3107
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to compare the number of CD57+ natural killer (NK) cells and CD8+ T lymphocytes between periapical granulomas (PGs) and radicular cysts (RCs). Twenty-fives cases of PGs and 25 of RCs were submitted to histological analysis and immunohistochemistry using anti-CD57 and anti-CD8 biomarkers. Positive cells were counted in 10 fields (400× magnification) and the median value was calculated for each case. Statistical tests were used to evaluate differences in the number of CD57+ NK cells and CD8+ T lymphocytes according to type of lesion, intensity of the infiltrate and thickness of the lining epithelium. The number of CD57+ NK cells and CD8+ T lymphocytes was higher in PGs than in RCs (p = 0.129 and p = 0.541, respectively). Comparison of the number of CD57+ NK cells in atrophic and hyperplastic epithelium revealed a larger number of cells in the atrophic epithelium (p = 0.042). A larger number of CD57+ NK cells and CD8+ T lymphocytes were observed in grade III infiltrates compared to grade I/II (p = 0.145 and p = 0.725, respectively). CD8+ T lymphocytes were more prevalent than CD57+ NK cells in most cases when PGs and RCs were analyzed separately or in combination (p < 0.0001). CD57+ NK cells and CD8+ T lymphocytes play a key role in antiviral defense and the presence of these cells supports evidence suggesting the participation of these microorganisms in the pathogenesis of PGs and RCs. The response mediated by CD8+ T lymphocytes was more frequent, indicating greater participation of the adaptive immunity in these chronic lesions.
[Mh] Termos MeSH primário: Antígenos CD57/análise
Linfócitos T CD8-Positivos/patologia
Células Matadoras Naturais/patologia
Granuloma Periapical/patologia
Cisto Radicular/patologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Biomarcadores/análise
Contagem de Células
Epitélio
Feminino
Seres Humanos
Imuno-Histoquímica
Masculino
Meia-Idade
Granuloma Periapical/imunologia
Cisto Radicular/imunologia
Valores de Referência
Índice de Gravidade de Doença
Estatísticas não Paramétricas
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (CD57 Antigens)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:D; IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE


  3 / 37711 MEDLINE  
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[PMID]:28468916
[Au] Autor:Vujanovic L; Stahl EC; Pardee AD; Geller DA; Tsung A; Watkins SC; Gibson GA; Storkus WJ; Butterfield LH
[Ad] Endereço:University of Pittsburgh Cancer Institute, University of Pittsburgh, Pennsylvania.
[Ti] Título:Tumor-Derived α-Fetoprotein Directly Drives Human Natural Killer-Cell Activation and Subsequent Cell Death.
[So] Source:Cancer Immunol Res;5(6):493-502, 2017 Jun.
[Is] ISSN:2326-6074
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatocellular carcinoma (HCC) patients with reduced natural killer (NK)-cell numbers and function have been shown to have a poor disease outcome. Mechanisms underlying NK-cell deficiency and dysfunction in HCC patients remain largely unresolved. α-Fetoprotein (AFP) is an oncofetal antigen produced by HCC. Previous studies demonstrated that tumor-derived AFP (tAFP) can indirectly impair NK-cell activity by suppressing dendritic cell function. However, a direct tAFP effect on NK cells remains unexplored. The purpose of this study was to examine the ability of cord blood-derived AFP (nAFP) and that of tAFP to directly modulate human NK-cell activity and longevity Short-term exposure to tAFP and, especially, nAFP proteins induced a unique proinflammatory, IL2-hyperresponsive phenotype in NK cells as measured by IL1ß, IL6, and TNF secretion, CD69 upregulation, and enhanced tumor cell killing. In contrast, extended coculture with tAFP, but not nAFP, negatively affected long-term NK-cell viability. NK-cell activation was directly mediated by the AFP protein itself, whereas their viability was affected by hydrophilic components within the low molecular mass cargo that copurified with tAFP. Identification of the distinct impact of circulating tAFP on NK-cell function and viability may be crucial to developing a strategy to ameliorate HCC patient NK-cell functional deficits. .
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/imunologia
Células Matadoras Naturais/imunologia
Neoplasias Hepáticas/imunologia
alfa-Fetoproteínas/imunologia
[Mh] Termos MeSH secundário: Morte Celular
Linhagem Celular Tumoral
Proliferação Celular
Células Cultivadas
Citocinas/imunologia
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AFP protein, human); 0 (Cytokines); 0 (alpha-Fetoproteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1158/2326-6066.CIR-16-0216


  4 / 37711 MEDLINE  
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[PMID]:29489682
[Au] Autor:Luo L; Wang H; Fan H; Xie J; Qiu Z; Li T
[Ad] Endereço:Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
[Ti] Título:The clinical characteristics and the features of immunophenotype of peripheral lymphocytes of adult onset chronic active Epstein-Barr virus disease at a Tertiary Care Hospital in Beijing.
[So] Source:Medicine (Baltimore);97(9):e9854, 2018 Mar.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease with high mortality. Most of CAEBV patients have been reported from Japan and are pediatric cases.The goal was to describe the clinical characteristics and the immunophenotypic features of peripheral lymphocytes in adult onset CAEBV patients.We retrospectively reviewed and analyzed all adult onset CAEBV cases admitted to Peking Union Medical College Hospital (PUMCH) between 2012 and 2016. Demographic, clinical, laboratory data, and the immunophentyping data of peripheral lymphocytes were collected.There were 28 adult onset CAEBV patients. The median age was 45 (range, 20-81). Most of the patients presented with fever; splenomegaly; lymphadenopathy and hepatitis. Unlike pediatric cases reported, the manifestations of cardiovascular diseases in our patients were pulmonary arterial hypertension, decreased cardiac function and aorta vasculitis. Prevalence of interstitial pneumonitis in our patients were comparatively higher and prevalence of hypersensitivity to mosquito bites were comparatively lower than that reported by Japan. In this study, CAEBV patients had decreased B cell, NK cell, CD4 cell and CD8 cell counts. The prevalence of low level of B cells, NK cells, CD4 cells was relatively higher than reported ever.Chinese adult onset CAEBV patients have different clinical characteristics and are featured by an immunosuppression status as demonstrated by decreased B cell, NK cell, CD4 cell and CD8 cell.
[Mh] Termos MeSH primário: Infecções por Vírus Epstein-Barr/imunologia
Herpesvirus Humano 4/imunologia
Imunofenotipagem
Contagem de Linfócitos
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Linfócitos B/imunologia
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
China
Doença Crônica
Infecções por Vírus Epstein-Barr/sangue
Feminino
Seres Humanos
Células Matadoras Naturais/imunologia
Masculino
Meia-Idade
Estudos Retrospectivos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180301
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009854


  5 / 37711 MEDLINE  
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[PMID]:28469292
[Au] Autor:Macek Jilkova Z; Decaens T; Marlu A; Marche H; Jouvin-Marche E; Marche PN
[Ad] Endereço:Université Grenoble-Alpes, IAB, 38000 Grenoble, France.
[Ti] Título:Sex Differences in Spontaneous Degranulation Activity of Intrahepatic Natural Killer Cells during Chronic Hepatitis B: Association with Estradiol Levels.
[So] Source:Mediators Inflamm;2017:3214917, 2017.
[Is] ISSN:1466-1861
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Major sex differences are observed in the prevalence, intensity, and severity of hepatitis B virus (HBV) infection. Here, we investigated degranulation activity of circulating and intrahepatic natural killer (NK) cells from HBV and HCV chronically infected patients before any treatment ( = 125). The frequency of CD107 NK cells in the female liver was significantly higher compared to that in males during chronic HBV infection ( = 0.002) and correlated with the plasma levels of estradiol (correlation coefficient = 0.634; < 0.0001). Our results clearly show sex differences in degranulation activity of intrahepatic NK cells of HBV-infected patients. This probably contributes to the ability of females to better deal with HBV disease.
[Mh] Termos MeSH primário: Estradiol/metabolismo
Hepatite B Crônica/metabolismo
Células Matadoras Naturais/metabolismo
Fígado/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular
Feminino
Citometria de Fluxo
Hepatite B Crônica/imunologia
Seres Humanos
Células Matadoras Naturais/citologia
Células Matadoras Naturais/imunologia
Fígado/citologia
Fígado/imunologia
Masculino
Fatores Sexuais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
4TI98Z838E (Estradiol)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1155/2017/3214917


  6 / 37711 MEDLINE  
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[PMID]:29352974
[Au] Autor:Sassi A; Maatouk M; El Gueder D; Bzéouich IM; Abdelkefi-Ben Hatira S; Jemni-Yacoub S; Ghedira K; Chekir-Ghedira L
[Ad] Endereço:Laboratory of Cellular and Molecular Biology, Faculty of Dental Medicine, University of Monastir, Avicenne Street, Monastir, 5000, Tunisia; Unity of Bioactive Natural Substances and Biotechnology, Faculty of Pharmacy, University of Monastir, Avicenne Street, Monastir, 5000, Tunisia.
[Ti] Título:Chrysin, a natural and biologically active flavonoid suppresses tumor growth of mouse B16F10 melanoma cells: In vitro and In vivo study.
[So] Source:Chem Biol Interact;283:10-19, 2018 Mar 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Chrysin (5,7-dihydroxyflavone) is a natural and biologically active compound which has many biological activities as an anticancer agent. The current report is aimed at finding out whether the antitumor potential of chrysin, evidenced in vitro and in vivo, is linked or not to its effect on immunological mechanisms of melanoma-bearing mice. Chrysin-treated B16F10 cells were analyzed for their metabolic rate and apoptotic potentials. In vivo, BALB/c mice received a subcutaneous injection of B16F10 melanoma cells prior to antitumor treatments with chrysin (50 mg/kg b.w) for 14 days and 21 days. The results showed that chrysin inhibited cancer cell growth at a dose-dependent manner by inducing apoptosis and cell cycle arrest at G2/M phase. Moreover, chrysin suppressed melanoma tumor growth at an average of 60% (after 14 days of treatment) and 71% (after 21 days of treatment) compared to the tumor-bearing group. Furthermore, chrysin treatment increased the cytotoxic activity of NK, CTL and macrophages. The findings showed that chrysin antitumor action on the murine melanoma model was very promising, suggesting that chrysin could be a potentially good candidate for future use in alternative anti-melanoma treatments.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Flavonoides/toxicidade
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Flavonoides/química
Flavonoides/uso terapêutico
Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos
Células Matadoras Naturais/citologia
Células Matadoras Naturais/imunologia
Células Matadoras Naturais/metabolismo
Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos
Macrófagos/citologia
Macrófagos/imunologia
Macrófagos/metabolismo
Masculino
Melanoma Experimental/tratamento farmacológico
Melanoma Experimental/metabolismo
Melanoma Experimental/patologia
Camundongos
Camundongos Endogâmicos BALB C
Óxido Nítrico/metabolismo
Linfócitos T Citotóxicos/citologia
Linfócitos T Citotóxicos/imunologia
Linfócitos T Citotóxicos/metabolismo
Transplante Homólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Flavonoids); 31C4KY9ESH (Nitric Oxide); 3CN01F5ZJ5 (chrysin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180122
[St] Status:MEDLINE


  7 / 37711 MEDLINE  
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[PMID]:28460478
[Au] Autor:Vo MC; Nguyen-Pham TN; Lee HJ; Jaya Lakshmi T; Yang S; Jung SH; Kim HJ; Lee JJ
[Ad] Endereço:Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea.
[Ti] Título:Combination therapy with dendritic cells and lenalidomide is an effective approach to enhance antitumor immunity in a mouse colon cancer model.
[So] Source:Oncotarget;8(16):27252-27262, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this study, we investigated efficacy of lenalidomide in combination with tumor antigen-loaded dendritic cells (DCs) in murine colon cancer model. MC-38 cell lines were injected subcutaneously to establish colon cancer-bearing mice. After tumor growth, lenalidomide (50 mg/kg/day) was injected intraperitoneally on 3 consecutive days in combination with tumor antigen-loaded DC vaccination on days 8, 12, 16, and 20. The tumor antigen-loaded DCs plus lenalidomide combination treatment exhibited a significant inhibition of tumor growth compared with the other groups. These effects were associated with a reduction in immune suppressor cells, such as myeloid-derived suppressor cells and regulatory T cells, with the induction of immune effector cells, such as natural killer cells, CD4+ T cells and CD8+ T cells in spleen, and with the activation of cytotoxic T lymphocytes and NK cells. This study suggests that a combination of tumor antigen-loaded DC vaccination and lenalidomide synergistically enhanced antitumor immune response in the murine colon cancer model, by inhibiting the generation of immune suppressive cells and recovery of effector cells, and demonstrated superior polarization of Th1/Th2 balance in favor of Th1 immune response. This combination approach with DCs and lenalidomide may provide a new therapeutic option to improve the treatment of colon cancer.
[Mh] Termos MeSH primário: Neoplasias do Colo/imunologia
Neoplasias do Colo/patologia
Células Dendríticas/imunologia
Imunidade
Talidomida/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Antígenos de Neoplasias/imunologia
Vacinas Anticâncer/administração & dosagem
Vacinas Anticâncer/imunologia
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Neoplasias do Colo/genética
Neoplasias do Colo/terapia
Terapia Combinada
Citocinas/biossíntese
Células Dendríticas/metabolismo
Modelos Animais de Doenças
Feminino
Expressão Gênica
Imunidade/efeitos dos fármacos
Imunoterapia
Células Matadoras Naturais/imunologia
Células Matadoras Naturais/metabolismo
Camundongos
Linfócitos T Citotóxicos/efeitos dos fármacos
Linfócitos T Citotóxicos/imunologia
Linfócitos T Citotóxicos/metabolismo
Linfócitos T Reguladores/efeitos dos fármacos
Linfócitos T Reguladores/imunologia
Linfócitos T Reguladores/metabolismo
Talidomida/farmacologia
Vacinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Neoplasm); 0 (Cancer Vaccines); 0 (Cytokines); 4Z8R6ORS6L (Thalidomide); F0P408N6V4 (lenalidomide)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15917


  8 / 37711 MEDLINE  
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[PMID]:27773685
[Au] Autor:Fehniger TA; Cooper MA
[Ad] Endereço:Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: tfehnige@wustl.edu.
[Ti] Título:Harnessing NK Cell Memory for Cancer Immunotherapy.
[So] Source:Trends Immunol;37(12):877-888, 2016 12.
[Is] ISSN:1471-4981
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Due to their ability to kill cancer cells and produce proinflammatory cytokines, natural killer (NK) cells have long been of clinical interest for their antitumor properties. The recent discovery of NK cell memory demonstrates that NK cell functions, and potentially antitumor responses, can be enhanced long term. Following nonspecific activation with the cytokines IL-12, IL-15, and IL-18 or in response to antigens or cytomegalovirus (CMV), human and mouse NK cells exhibit stable, enhanced functional responses with phenotypic and molecular changes. Here we review mechanisms driving the differentiation of NK cell memory-like properties, evidence for antitumor activity, and the challenges and opportunities in harnessing memory-like NK cells for cancer immunotherapy.
[Mh] Termos MeSH primário: Vacinas Anticâncer/imunologia
Memória Imunológica
Imunoterapia Adotiva/métodos
Células Matadoras Naturais/imunologia
Subpopulações de Linfócitos/imunologia
Neoplasias/terapia
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular
Citocinas/metabolismo
Citomegalovirus/imunologia
Citotoxicidade Imunológica
Seres Humanos
Mediadores da Inflamação/metabolismo
Células Matadoras Naturais/transplante
Ativação Linfocitária
Subpopulações de Linfócitos/transplante
Camundongos
Neoplasias/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cancer Vaccines); 0 (Cytokines); 0 (Inflammation Mediators)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


  9 / 37711 MEDLINE  
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[PMID]:28463694
[Au] Autor:Liu L; Yi H; He H; Pan H; Cai L; Ma Y
[Ad] Endereço:Key Lab of Health Informatics of Chinese Academy of Sciences, Guangdong Key Laboratory of Nanomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen 518055, PR China.
[Ti] Título:Tumor associated macrophage-targeted microRNA delivery with dual-responsive polypeptide nanovectors for anti-cancer therapy.
[So] Source:Biomaterials;134:166-179, 2017 Jul.
[Is] ISSN:1878-5905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Repolarizing Tumor-associated macrophages (TAMs) to anti-tumor M1 macrophages with microRNA (miR) is a plausible approach for cancer treatment. However, how to achieve TAM-targeted miR delivery remains a challenge. The present study generated redox/pH dual-responsive hybrid polypeptide nanovectors, which consisted of self-crosslinked redox-responsive nanoparticles based on galactose-functionalized n-butylamine-poly(l-lysine)-b-poly(l-cysteine) polypeptides (GLC) coated with DCA-grafted sheddable PEG-PLL (sPEG) copolymers. The ex vivo study showed that sPEG shielded cationic GLC core at physiological pH but quickly shed off to re-expose GLC due to it charge reversible property. Encapsulation with sPEG/GLC nanovectors effectively facilitated macrophage-targeted miR delivery at the acidic condition but diminished miR uptake at neutral pH. Administration of miR155-loaded sPEG/GLC (sPEG/GLC/155) nanocomplexes increased miR155 expression in TAMs about 100-400 folds both in vitro and in vivo. sPEG/GLC/155 also effectively repolarized immunosuppressive TAMs to anti-tumor M1 macrophages through elevating M1 macrophage markers (IL-12, iNOS, MHC II) and suppressing M2 macrophage markers (Msr2 and Arg1) in TAMs. Moreover, the treatment of sPEG/GLC/155 significantly increased activated T lymphocytes and NK cells in tumors, which consequently led to robust tumor regression. Hence, TAM-targeted delivery of miR with redox/pH dual-responsive sPEG/GLC nanovectors could be a promising approach to re-polarize TAMs to M1 macrophages in situ and induce tumor regression.
[Mh] Termos MeSH primário: MicroRNAs/genética
Nanopartículas/química
Peptídeos/química
[Mh] Termos MeSH secundário: Animais
Eletroforese em Gel de Ágar
Feminino
Interleucina-12/metabolismo
Células Matadoras Naturais/metabolismo
Espectroscopia de Ressonância Magnética
Melanoma/metabolismo
Melanoma/terapia
Melanoma Experimental
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Nus
MicroRNAs/fisiologia
Óxido Nítrico Sintase Tipo II/metabolismo
Células RAW 264.7
Transdução de Sinais/genética
Transdução de Sinais/fisiologia
Linfócitos T/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MicroRNAs); 0 (Peptides); 187348-17-0 (Interleukin-12); EC 1.14.13.39 (Nitric Oxide Synthase Type II)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:28460032
[Au] Autor:Knier B; Leppenetier G; Wetzlmair C; Aly L; Hoshi MM; Pernpeintner V; Biberacher V; Berthele A; Mühlau M; Zimmer C; Hemmer B; Korn T
[Ad] Endereço:Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany2Department of Experimental Neuroimmunology, Technische Universität München, Munich, Germany.
[Ti] Título:Association of Retinal Architecture, Intrathecal Immunity, and Clinical Course in Multiple Sclerosis.
[So] Source:JAMA Neurol;74(7):847-856, 2017 Jul 01.
[Is] ISSN:2168-6157
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Biomarkers to estimate long-term outcomes in patients with multiple sclerosis (MS) and to assign patients to individual treatment regimens are urgently needed. Objective: To assess whether retinal layer volumes are correlated with immune cell subsets and immunoglobulin indices in the cerebrospinal fluid and whether retinal layer volumes alone or in combination with intrathecal variables are associated with worsening of disease in patients with relapsing-remitting MS. Design, Setting, and Participants: This observational cohort study included 312 patients with relapsing-remitting MS in 2 independent cohorts (72 patients with short disease duration [cohort 1] and 240 patients with longer disease duration [cohort 2]) treated at a single German university hospital from April 15, 2013, through November 11, 2015. Main Outcomes and Measures: The common ganglion cell and inner plexiform layer (GCIPL) and inner nuclear layer (INL) volumes were tested for association with the immunoglobulin indices and the frequencies of immune cells in the cerebrospinal fluid (including B cells, T cells, and natural killer cells) (cohort 1). Volumes of GCIPL alone (cohorts 1 and 2) or GCIPL corrected for intrathecal B-cell frequencies (cohort 1) were tested for their association with worsening disability. Results: A total of 312 patients (212 women [67.9%] and 100 men [32.1%]; median age, 34.0 years [interquartile range (IQR), 28.0-42.0 years]) were available for analysis. In cohort 1 (50 women [69.4%] and 22 men [30.6%]; median age, 31.0 years [IQR, 26.3-38.3 years]), with short disease durations (median, 1.0 months [IQR, 1.0-2.0 months]), low GCIPL volumes were associated with increased intrathecal B-cell frequencies (median, 1.96% [IQR, 1.45%-4.20%]) and intrathecal IgG synthesis (median cerebrospinal fluid/serum IgG index, 0.78 [IQR, 0.53-1.07]). The INL volumes correlated with the frequencies of intrathecal CD56bright natural killer cells (r = 0.28; P = .007). Individuals with low GCIPL volumes (<1.99 mm3) had a 6.4-fold risk for worsening disability during follow-up compared with patients with higher GCIPL values (95% CI, 1.7-24.2; P = .007). This finding was reproduced in cohort 2 (162 women [67.5%] and 78 men [32.5%]; median age, 34.0 years [IQR, 29.0-42.0 years]) consisting of patients with longer disease durations (median, 36.0 months [IQR, 21.0-60.0 months]) (hazard ratio, 2.4; 95% CI, 1.2-4.8; P = .02). In both cohorts, INL volumes correlated with the prospective increase in T2 lesion load and the number of gadolinium-enhancing lesions. Conclusions and Relevance: Retinal layers reflect different aspects of disease activity during MS. Loss of GCIPL is associated with intrathecal B-cell immunity and constitutes an independent risk factor for worsening disability, whereas high INL volumes are associated with activity on magnetic resonance imaging in the brain parenchyma. Thus, retinal optical coherence tomography might be a means to support stratification of patients with MS for different therapeutic regimens.
[Mh] Termos MeSH primário: Líquido Cefalorraquidiano/imunologia
Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano
Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem
Esclerose Múltipla Recidivante-Remitente/fisiopatologia
Retina/diagnóstico por imagem
Células Ganglionares da Retina/patologia
[Mh] Termos MeSH secundário: Adulto
Atrofia/patologia
Linfócitos B
Biomarcadores
Feminino
Seres Humanos
Células Matadoras Naturais
Imagem por Ressonância Magnética
Masculino
Retina/citologia
Fatores de Risco
Linfócitos T
Tomografia de Coerência Óptica
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Biomarkers)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1001/jamaneurol.2017.0377



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