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[PMID]:28940014
[Au] Autor:Kato T; Miyoshi H; Kobayashi S; Yoshida N; Imaizumi Y; Seto M; Uchimaru K; Miyazaki Y; Ohshima K
[Ad] Endereço:Department of Pathology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
[Ti] Título:Clinicopathological analysis in PTCL-NOS with CADM1 expression.
[So] Source:Virchows Arch;471(5):659-666, 2017 Nov.
[Is] ISSN:1432-2307
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), is a heterogeneous disease with respect to clinicopathological features. Cell adhesion molecule 1 (CADM1) has been reported to be ectopically expressed in adult T cell leukaemia/lymphoma (ATLL). However, the frequency of CADM1 expression remains unknown in peripheral T cell lymphomas. In the current study, CADM1 expression was analysed in 88 PTCL-NOS patients. CADM1 was expressed in 14 of 88 (15.9%) PTCL-NOS cases, and its expression was associated with C-C chemokine receptor type 4 (CCR4) expression and nuclear atypia. CADM1-positive PTCL-NOS cases (10/74) had a significantly poorer prognosis than CADM1-negative cases (64/74) (P = 0.001). Multivariate analysis confirmed that CADM1 expression was an independent prognostic factor in PTCL-NOS. These findings suggest that CADM1 expression is a novel prognostic factor for PTCL-NOS.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/análise
Moléculas de Adesão Celular/biossíntese
Imunoglobulinas/biossíntese
Linfoma de Células T Periférico/patologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Molécula 1 de Adesão Celular
Moléculas de Adesão Celular/análise
Criança
Pré-Escolar
Feminino
Seres Humanos
Imunoglobulinas/análise
Estimativa de Kaplan-Meier
Linfoma de Células T Periférico/metabolismo
Linfoma de Células T Periférico/mortalidade
Masculino
Meia-Idade
Prognóstico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CADM1 protein, human); 0 (Cell Adhesion Molecule-1); 0 (Cell Adhesion Molecules); 0 (Immunoglobulins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170924
[St] Status:MEDLINE
[do] DOI:10.1007/s00428-017-2233-9


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[PMID]:28778448
[Au] Autor:Stüve O; Cataldi F; Pradhan V; Gorelick KJ
[Ad] Endereço:Neurology Section, VA North Texas Health Care System, Medical Service Dallas, VA Medical Center, United States; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States; Department of Neurology, Klinikum rechts der Isar, Tech
[Ti] Título:Normal intrathecal leukocyte cell number and composition do not decrease the incidence of post-lumbar puncture headache.
[So] Source:J Neuroimmunol;310:69-71, 2017 Sep 15.
[Is] ISSN:1872-8421
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The pathogenesis of post-lumbar puncture headache (PLPH) has remained unclear. A beneficial role of CSF cells in the repair of a post-traumatic dural CSF leak has been suggested. The primary purpose of this study was to investigate the effects of 8weeks of induction therapy with high-dose PF-00547659 on the cellular elements of CNS immune surveillance in patients with active Crohn's Disease and a history of immunosuppressive therapy (Clinicaltrials.govNCT01387594). PF-00547659 is a human monoclonal antibody that binds to mucosal addressin-cell adhesion molecule 1 (MAdCAM-1) on endothelial cells and blocks its interaction with beta7-integrin expressing lymphocytes. The study was executed in three parts or cohorts under two protocols. The incidence of a PLPH was 35% after the initial lumbar puncture, and 26% following the second lumbar puncture. After initiation of PF-00547659 anti-MAdCAM-1 therapy, there was a small and non-significant increase in the numbers of overall CSF leukocytes, and in lymphocyte subsets (CD3+, CD4+, and CD8+ T cells). The lymphocyte composition was unaltered by PF-00547659 anti-MAdCAM-1 therapy. Our observations suggest that normal numbers and composition of intrathecal leukocytes do not decrease the incidence of PLPH.
[Mh] Termos MeSH primário: Leucócitos/patologia
Cefaleia Pós-Punção Dural
[Mh] Termos MeSH secundário: Anticorpos Monoclonais Humanizados/uso terapêutico
Antígenos CD/metabolismo
Molécula 1 de Adesão Celular
Moléculas de Adesão Celular/metabolismo
Estudos de Coortes
Doença de Crohn/tratamento farmacológico
Feminino
Seres Humanos
Imunoglobulinas/metabolismo
Fatores Imunológicos/uso terapêutico
Incidência
Leucócitos/efeitos dos fármacos
Masculino
Cefaleia Pós-Punção Dural/líquido cefalorraquidiano
Cefaleia Pós-Punção Dural/tratamento farmacológico
Cefaleia Pós-Punção Dural/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Antigens, CD); 0 (CADM1 protein, human); 0 (Cell Adhesion Molecule-1); 0 (Cell Adhesion Molecules); 0 (Immunoglobulins); 0 (Immunologic Factors); 0 (PF-00547659)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170806
[St] Status:MEDLINE


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[PMID]:28724766
[Au] Autor:Ishihara Y; Tanaka Y; Kobayashi S; Kawamura K; Nakasone H; Gomyo A; Hayakawa J; Tamaki M; Akahoshi Y; Harada N; Kusuda M; Kameda K; Ugai T; Wada H; Sakamoto K; Sato M; Terasako-Saito K; Kikuchi M; Kimura SI; Tanihara A; Kako S; Uchimaru K; Kanda Y
[Ad] Endereço:Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
[Ti] Título:A Unique T-Cell Receptor Amino Acid Sequence Selected by Human T-Cell Lymphotropic Virus Type 1 Tax -Specific Cytotoxic T Cells in HLA-A24:02-Positive Asymptomatic Carriers and Adult T-Cell Leukemia/Lymphoma Patients.
[So] Source:J Virol;91(19), 2017 Oct 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We previously reported that the T-cell receptor (TCR) repertoire of human T-cell lymphotropic virus type 1 (HTLV-1) Tax -specific CD8 cytotoxic T cells (Tax -CTLs) was highly restricted and a particular amino acid sequence motif, the PDR motif, was conserved among HLA-A*24:02-positive (HLA-A*24:02 ) adult T-cell leukemia/lymphoma (ATL) patients who had undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-1. On the other hand, the TCR repertoires in Tax -CTLs of asymptomatic HTLV-1 carriers (ACs) remain unclear. In this study, we directly identified the DNA sequence of complementarity-determining region 3 (CDR3) of the TCR-ß chain of Tax -CTLs at the single-cell level and compared not only the TCR repertoires but also the frequencies and phenotypes of Tax -CTLs between ACs and ATL patients. We did not observe any essential difference in the frequencies of Tax -CTLs between ACs and ATL patients. In the single-cell TCR repertoire analysis of Tax -CTLs, 1,458 Tax -CTLs and 140 clones were identified in this cohort. Tax -CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-ß CDR3, was exclusively observed in all ACs and ATL patients. However, there was no correlation between PDR CTL frequencies and HTLV-1 proviral load (PVL). In conclusion, we have identified, for the first time, a unique amino acid sequence, PDR, as a public TCR-CDR3 motif against Tax in HLA-A*24:02 HTLV-1-infected individuals. Further investigations are warranted to elucidate the role of the PDR CTL response in the progression from carrier state to ATL. ATL is an aggressive T-cell malignancy caused by HTLV-1 infection. The HTLV-1 regulatory protein Tax aggressively promotes the proliferation of HTLV-1-infected lymphocytes and is also a major target antigen for CD8 CTLs. In our previous evaluation of Tax -CTLs, we found that a unique amino acid sequence motif, PDR, in CDR3 of the TCR-ß chain of Tax -CTLs was conserved among ATL patients after allo-HSCT. Furthermore, the PDR Tax -CTL clones selectively expanded and showed strong cytotoxic activities against HTLV-1. On the other hand, it remains unclear how Tax -CTL repertoire exists in ACs. In this study, we comprehensively compared Tax-specific TCR repertoires at the single-cell level between ACs and ATL patients. Tax -CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-ß CDR3, was conserved in all ACs and ATL patients, regardless of clinical subtype in HTLV-1 infection.
[Mh] Termos MeSH primário: Produtos do Gene tax/imunologia
Antígeno HLA-A24/imunologia
Vírus 1 Linfotrópico T Humano/imunologia
Leucemia-Linfoma de Células T do Adulto/imunologia
Receptores de Antígenos de Linfócitos T/imunologia
Linfócitos T Citotóxicos/imunologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos/genética
Antígenos CD7/metabolismo
Molécula 1 de Adesão Celular
Moléculas de Adesão Celular/metabolismo
Células Cultivadas
Produtos do Gene tax/genética
Antígeno HLA-A24/genética
Infecções por HTLV-I/patologia
Infecções por HTLV-I/virologia
Vírus 1 Linfotrópico T Humano/genética
Seres Humanos
Imunoglobulinas/metabolismo
Memória Imunológica/imunologia
Leucemia-Linfoma de Células T do Adulto/genética
Receptores de Antígenos de Linfócitos T/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD7); 0 (CADM1 protein, human); 0 (Cell Adhesion Molecule-1); 0 (Cell Adhesion Molecules); 0 (Gene Products, tax); 0 (HLA-A24 Antigen); 0 (Immunoglobulins); 0 (Receptors, Antigen, T-Cell); 0 (tax protein, Human T-lymphotrophic virus 1)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE


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[PMID]:28698142
[Au] Autor:Zhang J; Lai W; Li Q; Yu Y; Jin J; Guo W; Zhou X; Liu X; Wang Y
[Ad] Endereço:Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China. Electronic address: 704691556@qq.com.
[Ti] Título:A novel oncolytic adenovirus targeting Wnt signaling effectively inhibits cancer-stem like cell growth via metastasis, apoptosis and autophagy in HCC models.
[So] Source:Biochem Biophys Res Commun;491(2):469-477, 2017 Sep 16.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cancer stem cells (CSCs), which are highly differentiated and self-renewing, play an important role in the occurrence, therapeutic resistant and metastasis of hepatacellular carcinoma (HCC). Oncolytic adenoviruses have targeted killing effect on tumor cells, and are invoked as candidate drugs for cancer treatment. We designed a dual-regulated oncolytic adenovirus Ad.wnt-E1A(â–³24bp)-TSLC1 that targets Wnt and Rb signaling pathways respectively, and carries the tumor suppressor gene, TSLC1. Previous studies have demonstrated that oncolytic adenovirus mediated TSLC1can target liver cancer and exhibit significant cytotoxicity. However, whether Ad.wnt-E1A(â–³24bp)-TSLC1 can effectively eliminate liver CSCs remains to be explored. We first used the spheroid culture to enrich the liver CSCs-like cells, and detected the self-renewal capacity, differentiation, drug resistance and tumorigenicity. The results showed that Ad-wnt-E1A(â–³24bp)-TSLC1 could effectively lead to autophagic death. In addition, recombinant adenovirus effectively induced the apoptosis, inhibit metastasis of hepatic CSCs-like cells in vivo. Further animal experiments indicated that Ad-wnt-E1A(â–³24bp)-TSLC1could effectively inhibit the growth of transplanted tumor of hepatic CSCs and prolong the survival time of mice. Therefore, the novel oncolytic adenovirus Ad.wnt-E1A(â–³24bp)-TSLC1 has potential application as a therapeutic target for HCC stem cells.
[Mh] Termos MeSH primário: Adenoviridae/genética
Proteínas E1A de Adenovirus/genética
Carcinoma Hepatocelular/terapia
Moléculas de Adesão Celular/genética
Imunoglobulinas/genética
Neoplasias Hepáticas/terapia
Terapia Viral Oncolítica/métodos
Vírus Oncolíticos/genética
[Mh] Termos MeSH secundário: Adenoviridae/metabolismo
Proteínas E1A de Adenovirus/metabolismo
Animais
Autofagia
Carcinoma Hepatocelular/genética
Carcinoma Hepatocelular/mortalidade
Carcinoma Hepatocelular/patologia
Molécula 1 de Adesão Celular
Moléculas de Adesão Celular/metabolismo
Diferenciação Celular
Linhagem Celular Tumoral
Proliferação Celular
Feminino
Regulação da Expressão Gênica
Hepatócitos/metabolismo
Hepatócitos/patologia
Hepatócitos/virologia
Seres Humanos
Imunoglobulinas/metabolismo
Neoplasias Hepáticas/genética
Neoplasias Hepáticas/mortalidade
Neoplasias Hepáticas/patologia
Camundongos
Camundongos Nus
Células-Tronco Neoplásicas/metabolismo
Células-Tronco Neoplásicas/patologia
Células-Tronco Neoplásicas/virologia
Vírus Oncolíticos/metabolismo
Proteína do Retinoblastoma/genética
Proteína do Retinoblastoma/metabolismo
Transdução de Sinais
Análise de Sobrevida
Carga Tumoral
Proteínas Wnt/genética
Proteínas Wnt/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adenovirus E1A Proteins); 0 (CADM1 protein, human); 0 (Cell Adhesion Molecule-1); 0 (Cell Adhesion Molecules); 0 (Immunoglobulins); 0 (Retinoblastoma Protein); 0 (Wnt Proteins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170713
[St] Status:MEDLINE


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[PMID]:28651491
[Au] Autor:Takashima Y; Murakami T; Inoue T; Hagiyama M; Yoneshige A; Nishimura S; Akagi M; Ito A
[Ad] Endereço:1 Department of Pathology, Faculty of Medicine, Kindai University, Osaka, Japan.
[Ti] Título:Manifestation of osteoblastic phenotypes in the sarcomatous component of epithelial carcinoma and sarcomatoid carcinoma.
[So] Source:Tumour Biol;39(6):1010428317704365, 2017 Jun.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Epithelial carcinomas occasionally have sarcomatous components that consist primarily of spindle and cuboidal cells, which often resemble osteoblasts. Sarcomatoid carcinomas consist of similar cells. Recent studies have characterized these phenomena as a manifestation of epithelial-mesenchymal transition in carcinoma cells, but the mesenchymal phenotypes that manifest in sarcomatous cells of epithelial carcinomas are not well understood. Here, we examined the expression profiles of four osteoblastic differentiation biomarkers in the sarcomatous components of multiple carcinoma types, including five renal clear cell, four breast invasive ductal, two esophageal, one maxillary squamous cell, three larynx, three lung, one liver, and one skin sarcomatoid carcinoma. Expression was analyzed by immunohistochemistry using antibodies against cell adhesion molecule 1, a member of the IgCAM superfamily, osterix transcription factor (Osterix), cluster of differentiation 151, a transmembrane 4 superfamily member, and alkaline phosphatase. Immunostaining intensity was rated in scale 0 (negative), 0.5 (weak), and 1 (strong) for each marker, and the four scale values were summed to calculate osteoblastic scores. In all, 10 cases had a osteoblastic score ≥3, and all of these 10 cases were cell adhesion molecule 1- and Osterix-positive. Eight and five of the nine samples with a osteoblastic score <3 were negative for cell adhesion molecule 1 ( p < 0.0001) and Osterix ( p = 0.006), respectively. The other markers showed no statistical significance. These results indicate that osteoblastic differentiation can occur in carcinoma cells and that cell adhesion molecule 1 could be a useful marker for identifying this phenomenon in carcinoma tissues.
[Mh] Termos MeSH primário: Fosfatase Alcalina/biossíntese
Carcinoma/genética
Moléculas de Adesão Celular/biossíntese
Imunoglobulinas/biossíntese
Sarcoma/genética
Tetraspanina 24/biossíntese
Fatores de Transcrição/biossíntese
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Fosfatase Alcalina/genética
Biomarcadores Tumorais/biossíntese
Carcinoma/patologia
Molécula 1 de Adesão Celular
Moléculas de Adesão Celular/genética
Diferenciação Celular/genética
Transição Epitelial-Mesenquimal
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Imunoglobulinas/genética
Masculino
Meia-Idade
Neoplasias Epiteliais e Glandulares/genética
Neoplasias Epiteliais e Glandulares/patologia
Osteoblastos/patologia
Sarcoma/patologia
Fator de Transcrição Sp7
Tetraspanina 24/genética
Fatores de Transcrição/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CADM1 protein, human); 0 (CD151 protein, human); 0 (Cell Adhesion Molecule-1); 0 (Cell Adhesion Molecules); 0 (Immunoglobulins); 0 (Sp7 Transcription Factor); 0 (Sp7 protein, human); 0 (Tetraspanin 24); 0 (Transcription Factors); EC 3.1.3.1 (Alkaline Phosphatase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170628
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317704365


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[PMID]:28637314
[Au] Autor:Li L; Zheng H; Huang Y; Huang C; Zhang S; Tian J; Li P; Sood AK; Zhang W; Chen K
[Ad] Endereço:Department of Epidemiology and Biostatistics, Department of Urology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
[Ti] Título:DNA methylation signatures and coagulation factors in the peripheral blood leucocytes of epithelial ovarian cancer.
[So] Source:Carcinogenesis;38(8):797-805, 2017 Aug 01.
[Is] ISSN:1460-2180
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Solid tumors are increasingly recognized as a systemic disease that is manifested by changes in DNA, RNA, proteins and metabolites in the blood. Whereas many studies have reported gene mutation events in the circulation, few studies have focused on epigenetic DNA methylation markers. To identify DNA methylation biomarkers in peripheral blood for ovarian cancer, we performed a two-stage epigenome-wide association study. In the discovery stage, we measured genome wide DNA methylation for 485 000 CpG sites in peripheral blood in 24 epithelial ovarian cancer (EOC) cases and 24 age-matched healthy controls. We selected 96 significantly differentially methylated CpG sites for validation using Illumina's Custom VeraCode methylation assay in 206 EOC cases and 205 controls and 46 CpG sites validated in the independent replication samples. A set of 6 of these 46 CpG sites was found by the receiver operating characteristic analysis to have a prediction accuracy of 77.3% for all EOC (95% confidence interval: 72.9-81.8%). Pathway analysis of the genes associated with the 46 CpG sites revealed an enrichment of immune system process genes, including LYST (cg16962115, FDR = 1.24E-04), CADM1 (cg21933078, FDR = 1.22E-02) and NFATC1 (cg06784563, FDR = 1.46E-02). Furthermore, DNA methylation status in peripheral blood was correlated with platelet parameters/coagulation factor levels. This study discovered a panel of epigenetic liquid biopsy markers closely associated with overall immunologic conditions and platelet parameters/coagulation systems of the patients for detection of all stages and subtypes of EOC.
[Mh] Termos MeSH primário: Moléculas de Adesão Celular/genética
Metilação de DNA/genética
Imunoglobulinas/genética
Fatores de Transcrição NFATC/genética
Neoplasias Epiteliais e Glandulares/genética
Neoplasias Ovarianas/genética
Proteínas de Transporte Vesicular/genética
[Mh] Termos MeSH secundário: Biomarcadores Tumorais/sangue
Biomarcadores Tumorais/genética
Fatores de Coagulação Sanguínea/genética
Molécula 1 de Adesão Celular
Ilhas de CpG/genética
Epigênese Genética/genética
Feminino
Estudo de Associação Genômica Ampla
Seres Humanos
Leucócitos/metabolismo
Neoplasias Epiteliais e Glandulares/sangue
Neoplasias Epiteliais e Glandulares/patologia
Neoplasias Ovarianas/sangue
Neoplasias Ovarianas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Blood Coagulation Factors); 0 (CADM1 protein, human); 0 (Cell Adhesion Molecule-1); 0 (Cell Adhesion Molecules); 0 (Immunoglobulins); 0 (LYST protein, human); 0 (NFATC Transcription Factors); 0 (NFATC1 protein, human); 0 (Vesicular Transport Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE
[do] DOI:10.1093/carcin/bgx057


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[PMID]:28628102
[Au] Autor:Rathjen T; Yan X; Kononenko NL; Ku MC; Song K; Ferrarese L; Tarallo V; Puchkov D; Kochlamazashvili G; Brachs S; Varela L; Szigeti-Buck K; Yi CX; Schriever SC; Tattikota SG; Carlo AS; Moroni M; Siemens J; Heuser A; van der Weyden L; Birkenfeld AL; Niendorf T; Poulet JFA; Horvath TL; Tschöp MH; Heinig M; Trajkovski M; Haucke V; Poy MN
[Ad] Endereço:Max Delbrück Center for Molecular Medicine, Berlin, Germany.
[Ti] Título:Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1.
[So] Source:Nat Neurosci;20(8):1096-1103, 2017 Aug.
[Is] ISSN:1546-1726
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure. Loss of Cadm1 protected mice from obesity, and tract-tracing analysis revealed Cadm1-positive innervation of POMC neurons via afferent projections originating from beyond the arcuate nucleus. Reducing Cadm1 expression in the hypothalamus and hippocampus promoted a negative energy balance and weight loss. These data identify essential roles for Cadm1-mediated neuronal input in weight regulation and provide insight into the central pathways contributing to human obesity.
[Mh] Termos MeSH primário: Núcleo Arqueado do Hipotálamo/metabolismo
Peso Corporal/fisiologia
Moléculas de Adesão Celular Neuronais/genética
Moléculas de Adesão Celular/genética
Homeostase/genética
Imunoglobulinas/genética
Obesidade/metabolismo
[Mh] Termos MeSH secundário: Animais
Molécula 1 de Adesão Celular
Metabolismo Energético/fisiologia
Estudo de Associação Genômica Ampla
Homeostase/fisiologia
Proteínas de Membrana/metabolismo
Camundongos Transgênicos
Neurônios/metabolismo
Obesidade/genética
Pró-Opiomelanocortina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cadm1 protein, mouse); 0 (Cell Adhesion Molecule-1); 0 (Cell Adhesion Molecules); 0 (Cell Adhesion Molecules, Neuronal); 0 (Immunoglobulins); 0 (Membrane Proteins); 66796-54-1 (Pro-Opiomelanocortin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE
[do] DOI:10.1038/nn.4590


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[PMID]:28514904
[Au] Autor:Park SH; Sung YY; Nho KJ; Kim DS; Kim HK
[Ad] Endereço:* Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Republic of Korea.
[Ti] Título:Effects of Viola mandshurica on Atherosclerosis and Hepatic Steatosis in ApoE[Formula: see text] via the AMPK Pathway.
[So] Source:Am J Chin Med;45(4):757-772, 2017.
[Is] ISSN:0192-415X
[Cp] País de publicação:Singapore
[La] Idioma:eng
[Ab] Resumo:Atherosclerosis was previously thought to be a disease that primarily involves lipid accumulation in the arterial wall. In this report, we investigated the effect of Viola mandshurica W. Becker (V. mandshurica) water extract on atherosclerosis in apolipoprotein E deficient (ApoE[Formula: see text]) mice. The administration of V. mandshurica to high-fat diet-fed mice reduced body weight, liver weight, and serum levels of lipids (total cholesterol, low-density lipoprotein-cholesterol, triglycerides), glucose, alanine transaminase, and aspartate transaminase. Histopathologic analyses of the aorta and liver revealed that V. mandshurica attenuated atherosclerotic lesions and reduced lipid accumulation, inflammatory responses and fatty acid synthesis. V. mandshurica also increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), thereby reducing acetyl-CoA carboxylase (ACC) in liver tissue and inhibiting sterol regulatory element-binding protein 1c (SREBP-1c). V. mandshurica reduced protein expression levels of adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin) as well as ACC, fatty acid synthase, and SREBP-1c. In addition, quantitative analysis of V. mandshurica by high-performance liquid chromatography revealed the presence of esculetin and scopoletin. Esculetin and scopoletin reduced adhesion molecules in human aortic smooth muscle cells. Our results indicate that the anti-atherosclerotic effects of V. mandshurica may be associated with activation of the AMPK pathway. Therefore, AMPK-dependent phosphorylation of SREBP-1c by V. mandshurica may be an effective therapeutic strategy for combatting atherosclerosis and hepatic steatosis.
[Mh] Termos MeSH primário: Proteínas Quinases Ativadas por AMP/metabolismo
Aterosclerose/tratamento farmacológico
Aterosclerose/etiologia
Fígado Gorduroso/tratamento farmacológico
Fígado Gorduroso/etiologia
Terapia de Alvo Molecular
Fitoterapia
Extratos Vegetais/farmacologia
Extratos Vegetais/uso terapêutico
Viola/química
[Mh] Termos MeSH secundário: Acetil-CoA Carboxilase/metabolismo
Animais
Molécula 1 de Adesão Celular
Moléculas de Adesão Celular/metabolismo
Modelos Animais de Doenças
Imunoglobulinas/metabolismo
Metabolismo dos Lipídeos/efeitos dos fármacos
Fígado/metabolismo
Masculino
Camundongos Endogâmicos C57BL
Fosforilação/efeitos dos fármacos
Extratos Vegetais/química
Escopoletina/isolamento & purificação
Escopoletina/farmacologia
Escopoletina/uso terapêutico
Transdução de Sinais
Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
Umbeliferonas/isolamento & purificação
Umbeliferonas/farmacologia
Umbeliferonas/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cadm1 protein, mouse); 0 (Cell Adhesion Molecule-1); 0 (Cell Adhesion Molecules); 0 (Immunoglobulins); 0 (Plant Extracts); 0 (Srebf1 protein, mouse); 0 (Sterol Regulatory Element Binding Protein 1); 0 (Umbelliferones); EC 2.7.11.31 (AMP-Activated Protein Kinases); EC 6.4.1.2 (Acetyl-CoA Carboxylase); KLF1HS0SXJ (Scopoletin); SM2XD6V944 (esculetin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170519
[St] Status:MEDLINE
[do] DOI:10.1142/S0192415X17500409


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[PMID]:28510248
[Au] Autor:Qian JB; Liu HB; Zhu Y; Lu F; Yang QC; Shen Y
[Ad] Endereço:Department of Digestive Diseases, Nantong First People's Hospital, Nantong, Jiangsu, China.
[Ti] Título:CADM1 mRNA expression and clinicopathological significance in esophageal squamous cell carcinoma tissue.
[So] Source:Genet Mol Res;16(2), 2017 May 10.
[Is] ISSN:1676-5680
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:The mRNA expression of cell adhesion molecule 1 (CADM1) and its clinicopathological significance in esophageal squamous cell carcinoma (ESCC) tissues were investigated. CADM1 mRNA and protein expression were detected in tissue samples from 50 patients with ESCC by reverse transcription-polymerase chain reaction (RT-PCR) and streptavidin-peroxidase (SP) immunohistochemistry; adjacent tissues served as controls. The average CADM1 mRNA expression was significantly downregulated in the cancer tissues (0.522 ± 0.247) than in the controls (0.871 ± 0.192), (t = 7.882, P < 0.05). CADM1 mRNA expression was significantly downregulated in ESCC patients with positive lymph node metastasis than in those with negative lymph node metastasis (t = 3.207, P < 0.05). There was a correlation between CADM1 mRNA expression and tumor-node-metastasis (TNM) stage (t = 2.673, P < 0.050), but not with age, gender, and histological grade (P > 0.05). The positive expression rate of CADM1 protein in the 50 cases of ESCC was significantly lower than that of the control group (χ = 29.87, P < 0.01). Out of 28 patients with non-lymph node metastasis, 20 (71.43%) positively expressed CADM1; out of 22 patients with lymph node metastasis, only 7 (31.82%) positively expressed CADM1. There was a significant difference in the positive protein expression rates of CADM1 between the two groups (χ = 7.782, P < 0.01). CADM1 mRNA expression was highly upregulated in normal tissues compared to ESCC tissues, indicating that the loss of CADM1 expression influenced the pathogenesis, invasion, and metastasis of ESCC, and allowing for the prognosis of the disease in patients with ESCC after treatment.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Carcinoma de Células Escamosas/genética
Moléculas de Adesão Celular/genética
Neoplasias Esofágicas/genética
Imunoglobulinas/genética
RNA Mensageiro/genética
[Mh] Termos MeSH secundário: Idoso
Biomarcadores Tumorais/metabolismo
Carcinoma de Células Escamosas/metabolismo
Carcinoma de Células Escamosas/patologia
Molécula 1 de Adesão Celular
Moléculas de Adesão Celular/metabolismo
Neoplasias Esofágicas/metabolismo
Neoplasias Esofágicas/patologia
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Imunoglobulinas/metabolismo
Masculino
Meia-Idade
Metástase Neoplásica
RNA Mensageiro/metabolismo
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CADM1 protein, human); 0 (Cell Adhesion Molecule-1); 0 (Cell Adhesion Molecules); 0 (Immunoglobulins); 0 (RNA, Messenger)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170517
[St] Status:MEDLINE
[do] DOI:10.4238/gmr16029178


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[PMID]:28420814
[Au] Autor:Komohara Y; Ma C; Yano H; Pan C; Horlad H; Saito Y; Ohnishi K; Fujiwara Y; Okuno Y; Nosaka K; Shimosaki S; Morishita K; Matsuoka M; Wakayama T; Takeya M
[Ad] Endereço:Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University.
[Ti] Título:Cell adhesion molecule-1 (CADM1) expressed on adult T-cell leukemia/lymphoma cells is not involved in the interaction with macrophages.
[So] Source:J Clin Exp Hematop;57(1):15-20, 2017 Jul 05.
[Is] ISSN:1880-9952
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Cell adhesion molecule 1 (CADM1) is a cell adhesion molecule that is expressed in brain, liver, lung, testis, and some kinds of cancer cells including adult T-cell leukemia/lymphoma (ATLL). Recent studies have indicated the involvement of CADM1 in cell-cell contact between cytotoxic T-lymphocytes and virus infected cells. We previously reported that cell-cell interaction between lymphoma cells and macrophages induces lymphoma cell proliferation. In the present study, we investigated whether CADM1 is associated with cell-cell interaction between several human lymphoma cell lines and macrophages.CADM1 expression was observed in the ATLL cell lines, ATN-1, ATL-T, and ATL-35T, and in the B cell lymphoma cell lines, TL-1, DAUDI, and SLVL, using western blotting. Significant cell-cell interaction between macrophages and ATN-1, ATL-T, ATL-35T and MT-2, DAUDI, and SLVL cells, as assessed by induction of cell proliferation, was observed. Immunohistochemical analysis of human biopsy samples indicated CADM1 expression in 10 of 14 ATLL cases; however, no case of follicular lymphoma or diffuse large B-cell lymphoma was positive for CADM1. Finally, the interaction of macrophages with cells of the CADM1-negative ED ATLL cell line and CADM1-transfected ED cells was tested. However, significant cell-cell interaction between macrophage and CADM1-transfected ED cells was not observed. We conclude that CADM1 was not associated with cell-cell interaction between lymphoma cells and macrophages, although CADM1 may be a useful marker of ATLL for diagnostic procedures.
[Mh] Termos MeSH primário: Moléculas de Adesão Celular/metabolismo
Comunicação Celular
Imunoglobulinas/metabolismo
Leucemia-Linfoma de Células T do Adulto/metabolismo
Macrófagos/metabolismo
[Mh] Termos MeSH secundário: Biomarcadores Tumorais
Molécula 1 de Adesão Celular
Moléculas de Adesão Celular/genética
Comunicação Celular/genética
Linhagem Celular Tumoral
Células Cultivadas
Expressão Gênica
Seres Humanos
Imunoglobulinas/genética
Imuno-Histoquímica
Leucemia-Linfoma de Células T do Adulto/genética
Linfoma de Células B/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CADM1 protein, human); 0 (Cell Adhesion Molecule-1); 0 (Cell Adhesion Molecules); 0 (Immunoglobulins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170420
[St] Status:MEDLINE
[do] DOI:10.3960/jslrt.17003



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