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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


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[PMID]:29240761
[Au] Autor:Tomlinson MS; Bommarito PA; Martin EM; Smeester L; Fichorova RN; Onderdonk AB; Kuban KCK; O'Shea TM; Fry RC
[Ad] Endereço:Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.
[Ti] Título:Microorganisms in the human placenta are associated with altered CpG methylation of immune and inflammation-related genes.
[So] Source:PLoS One;12(12):e0188664, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Microorganisms in the placenta have been linked to adverse pregnancy outcomes as well as neonatal illness. Inflammation in the placenta has been identified as a contributing factor in this association, but the underlying biological mechanisms are not yet fully understood. The placental epigenome may serve as an intermediate between placental microbes and inflammation, contributing to adverse outcomes in the offspring. In the present study, genome-wide DNA methylation (n = 486,428 CpG sites) of 84 placentas was analyzed in relation to 16 species of placental microorganisms using samples collected from the Extremely Low Gestation Age Newborns (ELGAN) cohort. A total of n = 1,789 CpG sites, corresponding to n = 1,079 genes, displayed differential methylation (q<0.1) in relation to microorganisms. The altered genes encode for proteins that are involved in immune/inflammatory responses, specifically the NF-κB signaling pathway. These data support bacteria-dependent epigenetic patterning in the placenta and provide potential insight into mechanisms that associate the presence of microorganisms in the placenta to pregnancy and neonatal outcomes. This study lays the foundation for investigations of the placental microbiome and its role in placental function.
[Mh] Termos MeSH primário: Ilhas de CpG
Metilação de DNA
Imunidade/genética
Inflamação/genética
Placenta/microbiologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Feminino
Seres Humanos
Masculino
Meia-Idade
Gravidez
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188664


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[PMID]:28467380
[Au] Autor:Lin A; Truong B; Patel S; Kaushik N; Choi EH; Fridman G; Fridman A; Miller V
[Ad] Endereço:C. & J. Nyheim Plasma Institute, Drexel University, Philadelphia, PA 19104, USA. agl46@glink.drexel.edu.
[Ti] Título:Nanosecond-Pulsed DBD Plasma-Generated Reactive Oxygen Species Trigger Immunogenic Cell Death in A549 Lung Carcinoma Cells through Intracellular Oxidative Stress.
[So] Source:Int J Mol Sci;18(5), 2017 May 03.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:A novel application for non-thermal plasma is the induction of immunogenic cancer cell death for cancer immunotherapy. Cells undergoing immunogenic death emit danger signals which facilitate anti-tumor immune responses. Although pathways leading to immunogenic cell death are not fully understood; oxidative stress is considered to be part of the underlying mechanism. Here; we studied the interaction between dielectric barrier discharge plasma and cancer cells for oxidative stress-mediated immunogenic cell death. We assessed changes to the intracellular oxidative environment after plasma treatment and correlated it to emission of two danger signals: surface-exposed calreticulin and secreted adenosine triphosphate. Plasma-generated reactive oxygen and charged species were recognized as the major effectors of immunogenic cell death. Chemical attenuators of intracellular reactive oxygen species successfully abrogated oxidative stress following plasma treatment and modulated the emission of surface-exposed calreticulin. Secreted danger signals from cells undergoing immunogenic death enhanced the anti-tumor activity of macrophages. This study demonstrated that plasma triggers immunogenic cell death through oxidative stress pathways and highlights its potential development for cancer immunotherapy.
[Mh] Termos MeSH primário: Apoptose/imunologia
Imunoterapia/métodos
Neoplasias/terapia
Estresse Oxidativo/imunologia
Gases em Plasma/uso terapêutico
Espécies Reativas de Oxigênio/imunologia
[Mh] Termos MeSH secundário: Células A549
Trifosfato de Adenosina/metabolismo
Análise de Variância
Células Apresentadoras de Antígenos/metabolismo
Calreticulina/metabolismo
Condutividade Elétrica
Eletrodos
Seres Humanos
Imunidade
Quartzo/química
Espécies Reativas de Oxigênio/metabolismo
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calreticulin); 0 (Plasma Gases); 0 (Reactive Oxygen Species); 0 (calreticulin, human); 14808-60-7 (Quartz); 8L70Q75FXE (Adenosine Triphosphate)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


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[PMID]:28467354
[Au] Autor:Pal S; Meininger CJ; Gashev AA
[Ad] Endereço:Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center, Temple, TX 76504, USA. spal@medicine.tamhsc.edu.
[Ti] Título:Aged Lymphatic Vessels and Mast Cells in Perilymphatic Tissues.
[So] Source:Int J Mol Sci;18(5), 2017 May 03.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:This review provides a comprehensive summary of research on aging-associated alterations in lymphatic vessels and mast cells in perilymphatic tissues. Aging alters structure (by increasing the size of zones with low muscle cell investiture), ultrastructure (through loss of the glycocalyx), and proteome composition with a concomitant increase in permeability of aged lymphatic vessels. The contractile function of aged lymphatic vessels is depleted with the abolished role of nitric oxide and an increased role of lymphatic-born histamine in flow-dependent regulation of lymphatic phasic contractions and tone. In addition, aging induces oxidative stress in lymphatic vessels and facilitates the spread of pathogens from these vessels into perilymphatic tissues. Aging causes the basal activation of perilymphatic mast cells, which, in turn, restricts recruitment/activation of immune cells in perilymphatic tissues. This aging-associated basal activation of mast cells limits proper functioning of the mast cell/histamine/NF-κB axis that is essential for the regulation of lymphatic vessel transport and barrier functions as well as for both the interaction and trafficking of immune cells near and within lymphatic collecting vessels. Cumulatively, these changes play important roles in the pathogenesis of alterations in inflammation and immunity associated with aging.
[Mh] Termos MeSH primário: Envelhecimento/fisiologia
Imunidade/imunologia
Inflamação/imunologia
Vasos Linfáticos/fisiologia
Tecido Linfoide/fisiologia
[Mh] Termos MeSH secundário: Animais
Histamina/metabolismo
Seres Humanos
Mastócitos/metabolismo
Camundongos
NF-kappa B/metabolismo
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (NF-kappa B); 820484N8I3 (Histamine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


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[PMID]:29180807
[Au] Autor:Chiang JJ; Sparrer KMJ; van Gent M; Lässig C; Huang T; Osterrieder N; Hopfner KP; Gack MU
[Ad] Endereço:Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
[Ti] Título:Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity.
[So] Source:Nat Immunol;19(1):53-62, 2018 Jan.
[Is] ISSN:1529-2916
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The sensor RIG-I detects double-stranded RNA derived from RNA viruses. Although RIG-I is also known to have a role in the antiviral response to DNA viruses, physiological RNA species recognized by RIG-I during infection with a DNA virus are largely unknown. Using next-generation RNA sequencing (RNAseq), we found that host-derived RNAs, most prominently 5S ribosomal RNA pseudogene 141 (RNA5SP141), bound to RIG-I during infection with herpes simplex virus 1 (HSV-1). Infection with HSV-1 induced relocalization of RNA5SP141 from the nucleus to the cytoplasm, and virus-induced shutoff of host protein synthesis downregulated the abundance of RNA5SP141-interacting proteins, which allowed RNA5SP141 to bind RIG-I and induce the expression of type I interferons. Silencing of RNA5SP141 strongly dampened the antiviral response to HSV-1 and the related virus Epstein-Barr virus (EBV), as well as influenza A virus (IAV). Our findings reveal that antiviral immunity can be triggered by host RNAs that are unshielded following depletion of their respective binding proteins by the virus.
[Mh] Termos MeSH primário: Proteína DEAD-box 58/imunologia
Herpesvirus Humano 1/imunologia
Imunidade/imunologia
RNA Ribossômico 5S/imunologia
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Cercopithecus aethiops
Proteína DEAD-box 58/metabolismo
Expressão Gênica/imunologia
Células HEK293
Herpesvirus Humano 1/fisiologia
Interações Hospedeiro-Patógeno/imunologia
Seres Humanos
Interferon Tipo I/genética
Interferon Tipo I/imunologia
Interferon Tipo I/metabolismo
Camundongos Knockout
Pseudogenes/genética
Transporte de RNA/imunologia
RNA Ribossômico 5S/genética
RNA Ribossômico 5S/metabolismo
Células Vero
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interferon Type I); 0 (RNA, Ribosomal, 5S); EC 3.6.1.- (DDX58 protein, human); EC 3.6.4.13 (DEAD Box Protein 58)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.1038/s41590-017-0005-y


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[PMID]:28462526
[Au] Autor:Man SM; Karki R; Kanneganti TD
[Ad] Endereço:Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
[Ti] Título:Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases.
[So] Source:Immunol Rev;277(1):61-75, 2017 05.
[Is] ISSN:1600-065X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cell death is a fundamental biological phenomenon that is essential for the survival and development of an organism. Emerging evidence also indicates that cell death contributes to immune defense against infectious diseases. Pyroptosis is a form of inflammatory programmed cell death pathway activated by human and mouse caspase-1, human caspase-4 and caspase-5, or mouse caspase-11. These inflammatory caspases are used by the host to control bacterial, viral, fungal, or protozoan pathogens. Pyroptosis requires cleavage and activation of the pore-forming effector protein gasdermin D by inflammatory caspases. Physical rupture of the cell causes release of the pro-inflammatory cytokines IL-1ß and IL-18, alarmins and endogenous danger-associated molecular patterns, signifying the inflammatory potential of pyroptosis. Here, we describe the central role of inflammatory caspases and pyroptosis in mediating immunity to infection and clearance of pathogens.
[Mh] Termos MeSH primário: Caspases/metabolismo
Infecção/imunologia
Inflamassomos/metabolismo
Mediadores da Inflamação/metabolismo
Piroptose
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Imunidade
Interleucina-18/metabolismo
Interleucina-1beta/metabolismo
[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 (Inflammasomes); 0 (Inflammation Mediators); 0 (Interleukin-18); 0 (Interleukin-1beta); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1111/imr.12534


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[PMID]:29325417
[Au] Autor:Jiao J; Wu J; Wang M; Zhou C; Zhong R; Tan Z
[Ad] Endereço:Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, The Chinese Academy of Sciences ; National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production; Hunan Provincial Engineering Research Center for
[Ti] Título:Rhubarb Supplementation Promotes Intestinal Mucosal Innate Immune Homeostasis through Modulating Intestinal Epithelial Microbiota in Goat Kids.
[So] Source:J Agric Food Chem;66(4):1047-1057, 2018 Jan 31.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The abuse and misuse of antibiotics in livestock production pose a potential health risk globally. Rhubarb can serve as a potential alternative to antibiotics, and several studies have looked into its anticancer, antitumor, and anti-inflammatory properties. The aim of this study was to test the effects of rhubarb supplementation to the diet of young ruminants on innate immune function and epithelial microbiota in the small intestine. Goat kids were fed with a control diet supplemented with or without rhubarb (1.25% DM) and were slaughtered at days 50 and 60 of age. Results showed that the supplementation of rhubarb increased ileal villus height (P = 0.036), increased jejujal and ileal anti-inflammatory IL-10 production (P < 0.05), increased jejunal and ileal Claudin-1 expression at both mRNA and protein levels (P < 0.05), and decreased ileal pro-inflammatory IL-1ß production (P < 0.05). These changes in innate immune function were accompanied by shifts in ileal epithelial bacterial ecosystem in favor of Blautia, Clostridium, Lactobacillus, and Pseudomonas, and with a decline in the relative abundance of Staphylococcus (P < 0.001) when rhubarb was supplemented. Additionally, age also affected (P < 0.05) crypt depth, cytokine production, Claudin-1 expression and relative abundances of specific genera in epithelial bacteria. Collectively, the supplementation of rhubarb could enhance host mucosal innate immune homeostasis by modulating intestinal epithelial microbiota during the early stages of animal development.
[Mh] Termos MeSH primário: Dieta
Microbioma Gastrointestinal/efeitos dos fármacos
Cabras
Mucosa Intestinal/imunologia
Mucosa Intestinal/microbiologia
Rheum
[Mh] Termos MeSH secundário: Envelhecimento
Animais
Bactérias/classificação
Bactérias/isolamento & purificação
Claudina-1/análise
Claudina-1/genética
Citocinas/secreção
Microbioma Gastrointestinal/imunologia
Expressão Gênica/efeitos dos fármacos
Homeostase
Imunidade/efeitos dos fármacos
Mucosa Intestinal/crescimento & desenvolvimento
Intestino Delgado/efeitos dos fármacos
Intestino Delgado/crescimento & desenvolvimento
Intestino Delgado/microbiologia
RNA Mensageiro/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Claudin-1); 0 (Cytokines); 0 (RNA, Messenger)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b05297


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[PMID]:27776996
[Au] Autor:Holm HJ; Skugor S; Bjelland AK; Radunovic S; Wadsworth S; Koppang EO; Evensen Ø
[Ad] Endereço:Faculty of Veterinary Medicine and Biosciences, Department of Basic Sciences and Aquatic Medicine, Sea Lice Research Centre, Norwegian University of Life Sciences, Oslo, Norway. Electronic address: Helle.Holm@nmbu.no.
[Ti] Título:Contrasting expression of immune genes in scaled and scaleless skin of Atlantic salmon infected with young stages of Lepeophtheirus salmonis.
[So] Source:Dev Comp Immunol;67:153-165, 2017 02.
[Is] ISSN:1879-0089
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Atlantic salmon skin tissues with and without scales were taken from two preferred sites of salmon louse (Lepeophtheirus salmonis) attachment, behind the dorsal fin (scaled) and from the top of the head (scaleless), respectively. Tissues were profiled by qPCR of 32 genes to study responses to copepodids, 4 days post infection (dpi), and during the moult of copepodids to the chalimus stage, at 8 dpi. Basal/constitutive differences were found for many immune-related genes between the two skin sites; e.g., mannose binding protein C was over 100 fold higher expressed in the scaled skin from the back in comparison to the skin without scales from the head. With lice-infection, at 4 dpi most genes in both tissues showed lower values than in the non-infected control. By 8 dpi, the majority of responses increased towards the control levels, including cytokines of Th1, Th17 and Th2 pathways. Immunohistochemistry of three immune factors revealed an even distribution of MHC class II positive cells throughout epidermis, including the top layer of keratinocytes, marked compartmentalization of Mx and CD8α cells close to stratum basale, and an increase in numbers of CD8α cells in response to infection. In conclusion, suppression of immune genes during the copepodid stage likely sets off a beneficial situation for the parasite. At the moult to chalimus stage 8 dpi, only few genes surpassed the non-infected control levels, including CD8α. The gene expression pattern was reflected in the increased number of CD8α expressing cells, thus revealing a relatively minor activation of skin T-cell defenses in Atlantic salmon in response to L. salmonis infection.
[Mh] Termos MeSH primário: Escamas de Animais/fisiologia
Copépodes/imunologia
Proteínas de Peixes/metabolismo
Infestações por Piolhos/imunologia
Lectina de Ligação a Manose/metabolismo
Salmo salar/imunologia
Pele/imunologia
[Mh] Termos MeSH secundário: Escamas de Animais/parasitologia
Animais
Células Cultivadas
Citocinas/metabolismo
Proteínas de Peixes/genética
Imunidade/genética
Infestações por Piolhos/genética
Estágios do Ciclo de Vida
Lectina de Ligação a Manose/genética
Salmo salar/parasitologia
Pele/parasitologia
Fenômenos Fisiológicos da Pele/genética
Células Th1/imunologia
Células Th17/imunologia
Células Th2/imunologia
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cytokines); 0 (Fish Proteins); 0 (MBL2 protein, human); 0 (Mannose-Binding Lectin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180210
[Lr] Data última revisão:
180210
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:29193199
[Au] Autor:Liu C; Xie Y; Sun B; Geng F; Zhang F; Guo Q; Wu H; Yu B; Wu J; Yu X; Kong W; Zhang H
[Ad] Endereço:National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, Changchun, China.
[Ti] Título:MUC1- and Survivin-based DNA Vaccine Combining Immunoadjuvants CpG and interleukin-2 in a Bicistronic Expression Plasmid Generates Specific Immune Responses and Antitumour Effects in a Murine Colorectal Carcinoma Model.
[So] Source:Scand J Immunol;87(2):63-72, 2018 Feb.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:DNA vaccination is a promising cancer treatment due to its safety, but poor immunogenicity limits its application. However, immunoadjuvants, heterogeneous prime-boost strategies and combination with conventional treatments can be used to improve the antitumour immune effects. A CpG motif and interleukin-2 (IL-2) cytokine are often used as adjuvants. In this study, a DNA vaccine containing a CpG motif was constructed to evaluate its adjuvant effect. The results show that the cytotoxicity of the DNA vaccine was increased fivefold, and survival lifetime was prolonged twofold by the CpG motif adjuvant. To simplify the industrial production process, a bicistronic plasmid was constructed to carry the fusion genes of survivin/MUC1 (MS) and IL-2 and with a CpG motif in its backbone. The results showed that the antitumour effect of the bicistronic vaccine was the same as that of the two vaccine co-injected regime. Furthermore, the vaccine could suppress metastatic tumour foci by 69.1% in colorectal carcinoma-bearing mice. Moreover, the vaccine induced survivin- and MUC1-specific immune responses in splenocytes and induced the immune promoting factor CCL-19 and GM-CSF upregulated, while metastatic-associated factor MMP-9 and immunosuppressing factor PD-L1 downregulated in tumour tissue. When combining the vaccine with the chemotherapy drug oxaliplatin, the survival was prolonged by about 2.5-fold. In conclusion, the DNA vaccine containing a CpG motif in bicistronic form showed good effects on colorectal cancer by inhibiting both tumour growth and metastasis, and combination with oxaliplatin could improve its antitumour effects.
[Mh] Termos MeSH primário: Adjuvantes Imunológicos/genética
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Vacinas Anticâncer/imunologia
Neoplasias Colorretais/imunologia
Proteínas Inibidoras de Apoptose/genética
Mucina-1/genética
Oligodesoxirribonucleotídeos/genética
Compostos Organoplatínicos/uso terapêutico
Proteínas Repressoras/genética
Vacinas de DNA/imunologia
[Mh] Termos MeSH secundário: Animais
Vacinas Anticâncer/genética
Processos de Crescimento Celular
Linhagem Celular Tumoral
Neoplasias Colorretais/terapia
Modelos Animais de Doenças
Feminino
Genes/genética
Seres Humanos
Imunidade
Interleucina-2/administração & dosagem
Interleucina-2/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Metástase Neoplásica
Plasmídeos
Vacinas de DNA/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Birc5 protein, mouse); 0 (CPG-oligonucleotide); 0 (Cancer Vaccines); 0 (Inhibitor of Apoptosis Proteins); 0 (Interleukin-2); 0 (Mucin-1); 0 (Oligodeoxyribonucleotides); 0 (Organoplatinum Compounds); 0 (Repressor Proteins); 0 (Vaccines, DNA); 0 (muc1 protein, mouse); 04ZR38536J (oxaliplatin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12633


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[PMID]:29292195
[Au] Autor:Luo MT; Fan Y; Mu D; Yao YG; Zheng YT
[Ad] Endereço:Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Kunming College of Life Science, University of Chinese Ac
[Ti] Título:Molecular cloning and characterization of APOBEC3 family in tree shrew.
[So] Source:Gene;646:143-152, 2018 Mar 10.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The APOBEC3 family is a series antiviral factors that inhibit the replication of many viruses, such as HIV-1 and HBV. Tree shrews (Tupaia belangeri) possess great potential as an animal model for human diseases and therapeutic responses. However, the APOBEC3 family is unknown in tree shrews. Recent work has showed the presence of the APOBEC3 family in tree shrews. In this work, the cDNA sequences of five APOBEC3 members were identified in tree shrews, namely, tsAPOBEC3A, -3C, -3F, -3G and -3H. The results showed that their sequences encoded a zinc (Z)-coordinating-domain as a characteristic of APOBEC3 proteins. Phylogenetic analysis revealed that the tree shrew APOBEC3 (tsAPOBEC3) genes have occurred independently and that they are clustered with other mammalian APOBEC3 members. Transcript expression analysis indicated that tsAPOBEC3 genes are constitutively expressed, and high in immune-related tissues. tsAPOBEC3 gene expression was up-regulated in hepatocytes and PBMCs by IFN-α stimulation. Finally, tsAPOBEC3 proteins could edit both sides of DNA by inserting G→A and C→T hypermutations. Overall, the results suggest that the tsAPOBEC3 family could play a key role in defense immunity through distinct editing mechanisms. Our results provided insights into the genetic basis for the development of a tree shrew model for studying viral infection. Future studies will focus on deepening our understanding on the antiviral functions of these editing enzymes in tree shrew.
[Mh] Termos MeSH primário: Clonagem Molecular/métodos
Citidina Desaminase/genética
Citidina Desaminase/metabolismo
Tupaiidae/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sequência Conservada
Citidina Desaminase/química
Regulação Enzimológica da Expressão Gênica
Células Hep G2
Hepatócitos/metabolismo
Seres Humanos
Imunidade
Leucócitos Mononucleares/metabolismo
Família Multigênica
Filogenia
Domínios Proteicos
Distribuição Tecidual
Tupaiidae/genética
Tupaiidae/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.5.4.5 (Cytidine Deaminase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE



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