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[PMID]:28468645
[Au] Autor:Sæther SG; Schou M; Kondziella D
[Ad] Endereço:Department of Psychiatry, St. Olav's University Hospital, Pb. 3008, Lade, 7441, Trondheim, Norway. sverrege@gmail.com.
[Ti] Título:What is the significance of onconeural antibodies for psychiatric symptomatology? A systematic review.
[So] Source:BMC Psychiatry;17(1):161, 2017 05 03.
[Is] ISSN:1471-244X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Patients with intracellular onconeural antibodies may present with neuro-psychiatric syndromes. We aimed to evaluate the evidence for an association between well-characterized onconeural antibodies and psychiatric symptoms in patients with and without paraneoplastic central nervous system syndromes. METHODS: Eligible studies were selected from 1980 until February 2017 according to standardized review criteria and evaluated using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). We included studies describing the psychiatric symptomatology of onconeural antibody positive patients and the prevalence of onconeural antibodies in patients with psychiatric disorders. RESULTS: Twenty-seven studies met the inclusion criteria. Six studies reported on the prevalence of well-characterized onconeural antibodies in patients with different psychiatric disorders, ranging from 0% to 4.9%. Antibody prevalence in controls was available from three studies, ranging from 0% to 2.8%. Data heterogeneity precluded a meta-analysis. Two cerebrospinal fluid studies found well-characterized onconeural antibodies in 3.5% and 0% of patients with psychotic and depressive syndromes, respectively. CONCLUSIONS: The available evidence suggests that the prevalence of well-characterized onconeural antibodies in patients with psychiatric disorders is generally low. However, the question whether onconeural antibodies are important in select patients with a purely psychiatric phenotype needs to be addressed by appropriately designed studies in the future.
[Mh] Termos MeSH primário: Anticorpos Antineoplásicos/imunologia
Transtornos Mentais/psicologia
Síndromes Paraneoplásicas do Sistema Nervoso/psicologia
[Mh] Termos MeSH secundário: Seres Humanos
Transtornos Mentais/líquido cefalorraquidiano
Transtornos Mentais/imunologia
Síndromes Paraneoplásicas do Sistema Nervoso/líquido cefalorraquidiano
Síndromes Paraneoplásicas do Sistema Nervoso/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Neoplasm)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1186/s12888-017-1325-z


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[PMID]:28917835
[Au] Autor:Park H; Kim D; Son E; Shin S; Sa JK; Kim SH; Yoon Y; Nam DH
[Ad] Endereço:Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, Republic of Korea; Institute for Refractory Cancer Research, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Republic of Kor
[Ti] Título:Antitumor activity, pharmacokinetics, tumor-homing effect, and hepatotoxicity of a species cross-reactive c-Met antibody.
[So] Source:Biochem Biophys Res Commun;494(1-2):409-415, 2017 Dec 09.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The receptor tyrosine kinase c-Met plays critical roles in promoting tumor growth, invasion, metastasis, and angiogenesis in various types of cancer and is a promising therapeutic target. The development of a species cross-reactive therapeutic antibody could provide useful to comprehensive preclinical assessment in animal models. Towards this goal, we developed human/mouse cross-reactive c-Met antibodies using an antibody phage library. IRCR201, a c-Met antibody with species cross-reactivity, successfully inhibited the HGF/c-Met signaling pathway via degradation of c-Met and disruption of the binding with its partners, and demonstrated strong in vivo antitumor activity. In pharmacokinetic analysis, IRCR201 exhibited a nonlinear pharmacokinetic profile and showed rapid serum clearance at low dosage. Ex vivo fluorescence imaging and immunohistochemistry demonstrated strong tumor accumulation of IRCR201. Hepatotoxicity analysis revealed that IRCR201 does not significantly affect primary human and mouse hepatocytes. Serum chemistry analysis demonstrated that the alanine aminotransferase serum level was elevated in mice treated with 30 mg/kg IRCR201 than in PBS-treated mice, whereas the levels of aspartate aminotransferase and blood urea nitrogen did not significantly differ. Thus, IRCR201 is a potent therapeutic antibody that can disrupt the HGF/c-Met signaling axis and its species cross-reactivity would enable to evaluate precise biological activity in animal models.
[Mh] Termos MeSH primário: Anticorpos Antineoplásicos/farmacologia
Anticorpos Neutralizantes/farmacologia
Antineoplásicos/farmacologia
Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores
Neoplasias Gástricas/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacocinética
Linhagem Celular Tumoral
Reações Cruzadas
Células Epiteliais/citologia
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/imunologia
Feminino
Expressão Gênica
Hepatócitos/citologia
Hepatócitos/efeitos dos fármacos
Hepatócitos/imunologia
Seres Humanos
Injeções Intravenosas
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Neuroglia/citologia
Neuroglia/efeitos dos fármacos
Neuroglia/imunologia
Cultura Primária de Células
Proteínas Proto-Oncogênicas c-met/genética
Proteínas Proto-Oncogênicas c-met/imunologia
Transdução de Sinais
Neoplasias Gástricas/genética
Neoplasias Gástricas/imunologia
Neoplasias Gástricas/patologia
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neoplasm); 0 (Antibodies, Neutralizing); 0 (Antineoplastic Agents); EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170918
[St] Status:MEDLINE


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[PMID]:28898695
[Au] Autor:Bosse KR; Raman P; Zhu Z; Lane M; Martinez D; Heitzeneder S; Rathi KS; Kendsersky NM; Randall M; Donovan L; Morrissy S; Sussman RT; Zhelev DV; Feng Y; Wang Y; Hwang J; Lopez G; Harenza JL; Wei JS; Pawel B; Bhatti T; Santi M; Ganguly A; Khan J; Marra MA; Taylor MD; Dimitrov DS; Mackall CL; Maris JM
[Ad] Endereço:Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia,
[Ti] Título:Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma.
[So] Source:Cancer Cell;32(3):295-309.e12, 2017 Sep 11.
[Is] ISSN:1878-3686
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We developed an RNA-sequencing-based pipeline to discover differentially expressed cell-surface molecules in neuroblastoma that meet criteria for optimal immunotherapeutic target safety and efficacy. Here, we show that GPC2 is a strong candidate immunotherapeutic target in this childhood cancer. We demonstrate high GPC2 expression in neuroblastoma due to MYCN transcriptional activation and/or somatic gain of the GPC2 locus. We confirm GPC2 to be highly expressed on most neuroblastomas, but not detectable at appreciable levels in normal childhood tissues. In addition, we demonstrate that GPC2 is required for neuroblastoma proliferation. Finally, we develop a GPC2-directed antibody-drug conjugate that is potently cytotoxic to GPC2-expressing neuroblastoma cells. Collectively, these findings validate GPC2 as a non-mutated neuroblastoma oncoprotein and candidate immunotherapeutic target.
[Mh] Termos MeSH primário: Glipicanas/metabolismo
Imunoterapia
Terapia de Alvo Molecular
Neuroblastoma/imunologia
Neuroblastoma/terapia
Proteínas Oncogênicas/metabolismo
[Mh] Termos MeSH secundário: Animais
Anticorpos Antineoplásicos/metabolismo
Morte Celular
Linhagem Celular Tumoral
Membrana Celular/metabolismo
Proliferação Celular
Criança
Regulação Neoplásica da Expressão Gênica
Genoma Humano
Seres Humanos
Camundongos Endogâmicos NOD
Camundongos SCID
Proteína Proto-Oncogênica N-Myc/metabolismo
Neuroblastoma/genética
Neuroblastoma/patologia
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neoplasm); 0 (GPC2 protein, human); 0 (Glypicans); 0 (MYCN protein, human); 0 (N-Myc Proto-Oncogene Protein); 0 (Oncogene Proteins); 0 (RNA, Messenger)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE


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[PMID]:28686661
[Au] Autor:Kim MA; Yoon HS; Park SH; Kim DY; Pyo A; Kim HS; Min JJ; Hong Y
[Ad] Endereço:Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
[Ti] Título:Engineering of monobody conjugates for human EphA2-specific optical imaging.
[So] Source:PLoS One;12(7):e0180786, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In a previous study, we developed an E1 monobody specific for the tumor biomarker hEphA2 [PLoS ONE (2015) 10(7): e0132976]. E1 showed potential as a molecular probe for in vitro and in vivo targeting of cancers overexpressing hEphA2. In the present study, we constructed expression vectors for E1 conjugated to optical reporters such as Renilla luciferase variant 8 (Rluc8) or enhanced green fluorescent protein (EGFP) and purified such recombinant proteins by affinity chromatography in E. coli. E1-Rluc8 and E1-EGFP specifically bound to hEphA2 in human prostate cancer PC3 cells but not in human cervical cancer HeLa cells, which express hEphA2 at high and low levels, respectively. These recombinant proteins maintained >40% activity in mouse serum at 24 h. In vivo optical imaging for 24 h did not detect E1-EGFP signals, whereas E1-Rluc8 showed tumor-specific luminescence signals in PC3 but not in HeLa xenograft mice. E1-Rluc8 signals were detected at 4 h, peaked at 12 h, and were undetectable at 24 h. These results suggest the potential of E1-Rluc8 as an EphA2-specific optical imaging agent.
[Mh] Termos MeSH primário: Anticorpos Antineoplásicos/química
Biomarcadores Tumorais/análise
Imunoconjugados/química
Receptor EphA2/análise
Proteínas Recombinantes de Fusão/genética
[Mh] Termos MeSH secundário: Animais
Anticorpos Antineoplásicos/biossíntese
Biomarcadores Tumorais/genética
Biomarcadores Tumorais/metabolismo
Linhagem Celular Tumoral
Escherichia coli/genética
Escherichia coli/metabolismo
Feminino
Genes Reporter
Vetores Genéticos/química
Vetores Genéticos/metabolismo
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Células HeLa
Xenoenxertos
Seres Humanos
Imunoconjugados/metabolismo
Luciferases/genética
Luciferases/metabolismo
Masculino
Camundongos Endogâmicos BALB C
Camundongos Nus
Imagem Óptica
Especificidade de Órgãos
Engenharia de Proteínas
Receptor EphA2/genética
Receptor EphA2/metabolismo
Proteínas Recombinantes de Fusão/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neoplasm); 0 (Biomarkers, Tumor); 0 (Immunoconjugates); 0 (Recombinant Fusion Proteins); 0 (enhanced green fluorescent protein); 147336-22-9 (Green Fluorescent Proteins); EC 1.13.12.- (Luciferases); EC 2.7.10.1 (Receptor, EphA2)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180786


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[PMID]:28619621
[Au] Autor:Valmary-Degano S; Colpart P; Villeneuve L; Monnien F; M'Hamdi L; Lang Averous G; Capovilla M; Bibeau F; Laverriere MH; Verriele-Beurrier V; Ben Rejeb H; Dartigues P; Hommell-Fontaine J; Gilly FN; Isaac S; Mery E; French RENAPE Network
[Ad] Endereço:Department of Pathology, Besançon University Hospital, 3 Boulevard Fleming, F-25030, Besançon, France; University of Bourgogne Franche-Comté, F-25000, Besançon, France. Electronic address: svalmary@univ-fcomte.fr.
[Ti] Título:Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study.
[So] Source:Eur J Surg Oncol;43(10):1915-1923, 2017 Oct.
[Is] ISSN:1532-2157
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Epithelioid peritoneal malignant mesothelioma (EPMM) is the most common subtype of this aggressive tumor. We compared two antibodies against PD-L1, a recent theranostic biomarker, and evaluated the prognostic value of PD-L1 expression by mesothelial and immune cells in EPMM. METHODS: Immunohistochemistry was performed on 45 EPMM. Clinical and pathological data were extracted from the RENAPE database. Using E1L3N and SP142 clones, inter-observer agreement, PD-L1 expression by mesothelial and immune cells and inter-antibody agreement were evaluated. The prognostic relevance of PD-L1 expression was evaluated in 39 EPMM by univariate and multivariate analysis of overall survival (OS) and progression-free survival (PFS). RESULTS: Inter-observer agreement on E1L3N immunostaining was moderate for mesothelial and immune cells, and fair for mesothelial and poor for immune cells using SP142. Using E1L3N, 31.1% of mesothelial and 15.6% of immune cells expressed PD-L1, and 22.2% of mesothelial and 26.7% of immune cells using SP142. Inter-antibody agreement was moderate. In most positive cases, 1-5% of tumor cells were positive. Using E1L3N, PD-L1 expression by lymphocytes was associated with better OS and PFS by both univariate and multivariate analysis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy predicted better prognosis than other treatments. Solid subtype was an independent prognostic factor for worse OS. CONCLUSION: E1L3N appeared easier to use than SP142 to evaluate PD-L1 expression. A minority of EPMM expressed PD-L1, and only a few cells were positive. PD-L1 expression by immune cells evaluated with E1L3N was an independent prognostic factor in EPMM.
[Mh] Termos MeSH primário: Anticorpos Antineoplásicos/metabolismo
Antígeno B7-H1/imunologia
Imunidade Celular
Imuno-Histoquímica/métodos
Mesotelioma/imunologia
Neoplasias Peritoneais/imunologia
[Mh] Termos MeSH secundário: Anticorpos Antineoplásicos/imunologia
Antígeno B7-H1/biossíntese
Biomarcadores Tumorais/imunologia
Biomarcadores Tumorais/metabolismo
Feminino
Seguimentos
França/epidemiologia
Seres Humanos
Linfócitos/imunologia
Linfócitos/metabolismo
Masculino
Mesotelioma/metabolismo
Mesotelioma/mortalidade
Meia-Idade
Neoplasias Peritoneais/metabolismo
Neoplasias Peritoneais/mortalidade
Prognóstico
Estudos Retrospectivos
Taxa de Sobrevida/tendências
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Antibodies, Neoplasm); 0 (B7-H1 Antigen); 0 (Biomarkers, Tumor); 0 (CD274 protein, human)
[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:170617
[St] Status:MEDLINE


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[PMID]:28617827
[Au] Autor:Kametani Y; Katano I; Miyamoto A; Kikuchi Y; Ito R; Muguruma Y; Tsuda B; Habu S; Tokuda Y; Ando K; Ito M
[Ad] Endereço:Department of Molecular Life Science, Division of Basic Medical Science, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
[Ti] Título:NOG-hIL-4-Tg, a new humanized mouse model for producing tumor antigen-specific IgG antibody by peptide vaccination.
[So] Source:PLoS One;12(6):e0179239, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMCs) are promising tools to evaluate human immune responses to vaccines. However, these mice usually develop severe graft-versus-host disease (GVHD), which makes estimation of antigen-specific IgG production after antigen immunization difficult. To evaluate antigen-specific IgG responses in PBMC-transplanted immunodeficient mice, we developed a novel NOD/Shi-scid-IL2rγnull (NOG) mouse strain that systemically expresses the human IL-4 gene (NOG-hIL-4-Tg). After human PBMC transplantation, GVHD symptoms were significantly suppressed in NOG-hIL-4-Tg compared to conventional NOG mice. In kinetic analyses of human leukocytes, long-term engraftment of human T cells has been observed in peripheral blood of NOG-hIL-4-Tg, followed by dominant CD4+ T rather than CD8+ T cell proliferation. Furthermore, these CD4+ T cells shifted to type 2 helper (Th2) cells, resulting in long-term suppression of GVHD. Most of the human B cells detected in the transplanted mice had a plasmablast phenotype. Vaccination with HER2 multiple antigen peptide (CH401MAP) or keyhole limpet hemocyanin (KLH) successfully induced antigen-specific IgG production in PBMC-transplanted NOG-hIL-4-Tg. The HLA haplotype of donor PBMCs might not be relevant to the antibody secretion ability after immunization. These results suggest that the human PBMC-transplanted NOG-hIL-4-Tg mouse is an effective tool to evaluate the production of antigen-specific IgG antibodies.
[Mh] Termos MeSH primário: Anticorpos Antineoplásicos/imunologia
Formação de Anticorpos
Proteínas de Transporte/imunologia
Imunização
Imunoglobulina G/imunologia
Interleucina-4/imunologia
Peptídeos/farmacologia
Receptor ErbB-2/farmacologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antineoplásicos/genética
Linfócitos B/imunologia
Linfócitos B/transplante
Linfócitos T CD8-Positivos/imunologia
Linfócitos T CD8-Positivos/transplante
Proteínas de Transporte/genética
Xenoenxertos
Seres Humanos
Imunoglobulina G/genética
Interleucina-4/genética
Camundongos
Camundongos SCID
Camundongos Transgênicos
Peptídeos/imunologia
Receptor ErbB-2/imunologia
Células Th2/imunologia
Células Th2/transplante
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neoplasm); 0 (Carrier Proteins); 0 (IL4 protein, human); 0 (Immunoglobulin G); 0 (Peptides); 148294-77-3 (noggin protein); 207137-56-2 (Interleukin-4); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170913
[Lr] Data última revisão:
170913
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170616
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179239


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[PMID]:28606939
[Au] Autor:Pereira RM; Hogan PG; Rao A; Martinez GJ
[Ad] Endereço:Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; renata.pereira@micro.ufrj.br.
[Ti] Título:Transcriptional and epigenetic regulation of T cell hyporesponsiveness.
[So] Source:J Leukoc Biol;102(3):601-615, 2017 Sep.
[Is] ISSN:1938-3673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Naive CD8 T cells differentiate into effector and memory cytolytic T cells (CTLs) during an acute infection. In contrast, in scenarios of persistent antigen stimulation, such as chronic infections and cancer, antigen-specific CTLs show a gradual decrease in effector function, a phenomenon that has been termed CD8 T cell "exhaustion" or "dysfunction." Another hyporesponsive state, termed "anergy", is observed when T cells are activated in the absence of positive costimulatory signals. Among the many negative regulators induced in hyporesponsive T cells are inhibitory cell-surface receptors, such as PD-1, LAG-3, CTLA-4, and TIM-3; "checkpoint blockade" therapies that involve treatment of patients with cancer with blocking antibodies to those receptors show considerable promise in the clinic because the blocking antibodies can mitigate hyporesponsiveness and promote tumor rejection. In this review, we describe recent advances in our molecular understanding of these hyporesponsive states. We review evidence for the involvement of diverse transcription factors, metabolic programs, and chromatin accessibility changes in hyporesponsive T cells, and we discuss how checkpoint blockade therapies affect the molecular program of CD8 T cell exhaustion.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Epigênese Genética/imunologia
Memória Imunológica
Neoplasias/imunologia
Fatores de Transcrição/imunologia
Transcrição Genética/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antineoplásicos/imunologia
Anticorpos Antineoplásicos/uso terapêutico
Anticorpos Neutralizantes/imunologia
Anticorpos Neutralizantes/uso terapêutico
Linfócitos T CD8-Positivos/patologia
Seres Humanos
Neoplasias/patologia
Neoplasias/terapia
Receptores de Superfície Celular/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Neoplasm); 0 (Antibodies, Neutralizing); 0 (Receptors, Cell Surface); 0 (Transcription Factors)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170614
[St] Status:MEDLINE
[do] DOI:10.1189/jlb.2RI0317-097R


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[PMID]:28560680
[Au] Autor:Wang D; Wu L; Liu X
[Ad] Endereço:Tumor Glycomics Laboratory, Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park, CA, 94025-3493, USA. denong.wang@sri.com.
[Ti] Título:Glycan Markers as Potential Immunological Targets in Circulating Tumor Cells.
[So] Source:Adv Exp Med Biol;994:275-284, 2017.
[Is] ISSN:0065-2598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We present here an experimental approach for exploring a new class of tumor biomarkers that are overexpressed by circulating tumor cells (CTCs) and are likely targetable in immunotherapy against tumor metastasis. Using carbohydrate microarrays, anti-tumor monoclonal antibodies (mAbs) were scanned against a large panel of carbohydrate antigens to identify potential tumor glycan markers. Subsequently, flow cytometry and fiber-optic array scanning technology (FAST) were applied to determine whether the identified targets are tumor-specific cell-surface markers and are, therefore, likely suitable for targeted immunotherapy. Finally, the tumor glycan-specific antibodies identified were validated using cancer patients' blood samples for their performance in CTC-detection and immunotyping analysis. In this article, identifying breast CTC-specific glycan markers and targeting mAbs serve as examples to illustrate this tumor biomarker discovery strategy.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Neoplasias/sangue
Células Neoplásicas Circulantes/metabolismo
Polissacarídeos/sangue
[Mh] Termos MeSH secundário: Anticorpos Antineoplásicos/química
Seres Humanos
Imunoterapia/métodos
Neoplasias/terapia
Análise Serial de Proteínas/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Neoplasm); 0 (Biomarkers, Tumor); 0 (Polysaccharides)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170601
[St] Status:MEDLINE
[do] DOI:10.1007/978-3-319-55947-6_15


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[PMID]:28427776
[Au] Autor:Katchman BA; Chowell D; Wallstrom G; Vitonis AF; LaBaer J; Cramer DW; Anderson KS
[Ad] Endereço:Virginia G. Piper Center for Personal Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
[Ti] Título:Autoantibody biomarkers for the detection of serous ovarian cancer.
[So] Source:Gynecol Oncol;146(1):129-136, 2017 Jul.
[Is] ISSN:1095-6859
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Objective The purpose of this study was to identify a panel of novel serum tumor antigen-associated autoantibody (TAAb) biomarkers for the diagnosis of high-grade serous ovarian cancer. METHODS: To detect TAAb we probed high-density programmable protein microarrays (NAPPA) containing 10,247 antigens with sera from patients with serous ovarian cancer (n=30 cases/30 healthy controls) and measured bound IgG. We identified 735 promising tumor antigens and evaluated these with an independent set of serous ovarian cancer sera (n=30 cases/30 benign disease controls/30 healthy controls). Thirty-nine potential tumor autoantigens were identified and evaluated using an orthogonal programmable ELISA platform against a total of 153 sera samples (n=63 cases/30 benign disease controls/60 healthy controls). Sensitivities at 95% specificity were calculated and a classifier for the detection of high-grade serous ovarian cancer was constructed. RESULTS: We identified 11-TAAbs (ICAM3, CTAG2, p53, STYXL1, PVR, POMC, NUDT11, TRIM39, UHMK1, KSR1, and NXF3) that distinguished high-grade serous ovarian cancer cases from healthy controls with a combined 45% sensitivity at 98% specificity. CONCLUSION: These are potential circulating biomarkers for the detection of serous ovarian cancer, and warrant confirmation in larger clinical cohorts.
[Mh] Termos MeSH primário: Anticorpos Antineoplásicos/sangue
Autoanticorpos/sangue
Biomarcadores Tumorais/imunologia
Cistadenocarcinoma Seroso/imunologia
Neoplasias Ovarianas/imunologia
[Mh] Termos MeSH secundário: Anticorpos Antineoplásicos/imunologia
Antígenos de Neoplasias/sangue
Antígenos de Neoplasias/imunologia
Autoanticorpos/imunologia
Biomarcadores Tumorais/sangue
Estudos de Casos e Controles
Cistadenocarcinoma Seroso/sangue
Feminino
Seres Humanos
Meia-Idade
Neoplasias Ovarianas/sangue
Análise Serial de Proteínas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neoplasm); 0 (Antigens, Neoplasm); 0 (Autoantibodies); 0 (Biomarkers, Tumor)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170722
[Lr] Data última revisão:
170722
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[St] Status:MEDLINE


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[PMID]:28408397
[Au] Autor:Ferretti E; Corcione A; Pistoia V
[Ad] Endereço:Laboratory of Oncology, Istituto Giannina Gaslini, Genova, Italy; and.
[Ti] Título:The IL-31/IL-31 receptor axis: general features and role in tumor microenvironment.
[So] Source:J Leukoc Biol;102(3):711-717, 2017 Sep.
[Is] ISSN:1938-3673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:IL-31 is a recently identified cytokine with a well-defined role in the pathogenesis of pruritus. IL-31, whose production is induced by IL-4 and IL-33, binds a heterodimeric receptor (R) composed of the exclusive IL-31RA chain and the shared oncostatin M R. Signaling through the IL-31R involves the MAPK, PI3K/AKT and Jak/STAT pathways. Different variants and isoforms of IL-31RA with different signaling activities have been identified. IL-31 is produced predominantly by circulating Th2 lymphocytes and skin-homing CLA CD45RO T cells. Studies in humans have demonstrated a pathogenic role for IL-31 in atopic dermatitis and allergic asthma. The first demonstration of the involvement of the IL-31/IL-31R axis in cancer came from studies in patients with mycosis fungoides/Sézary syndrome, the most frequent, cutaneous T cell lymphoma. Tumor cells were shown to produce IL-31, whose serum levels correlated with pruritus intensity. Follicular lymphoma (FL) B cells and their counterparts-germinal center B cells-produced IL-31 and expressed IL-31R, which signaled in the former, but not the latter, cells. IL-31 released in association with microvesicles promoted tumor growth through autocrine/paracrine loops. Malignant mast cells from patients with mastocytosis or Philadelphia-negative myeloproliferative disorder produced IL-31, which contributed to pruritus pathogenesis. Finally, patients with endometrial carcinoma displayed high serum levels of IL-31 and IL-33, which may represent promising disease biomarkers. Targeting strategies for the IL-31/IL-31R axis have been developed, including the CIMM331 humanized anti-human IL-31RA antibody recently tested in a phase I/Ib study.
[Mh] Termos MeSH primário: Interleucinas/imunologia
Sistema de Sinalização das MAP Quinases/imunologia
Neoplasias/imunologia
Receptores de Interleucina/imunologia
Microambiente Tumoral/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais Humanizados/uso terapêutico
Anticorpos Antineoplásicos/uso terapêutico
Linfócitos B/imunologia
Linfócitos B/patologia
MAP Quinases Reguladas por Sinal Extracelular/imunologia
Seres Humanos
Interleucinas/antagonistas & inibidores
Janus Quinases/imunologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Neoplasias/tratamento farmacológico
Neoplasias/patologia
Fosfatidilinositol 3-Quinases/imunologia
Proteínas Proto-Oncogênicas c-akt/imunologia
Fatores de Transcrição STAT/imunologia
Microambiente Tumoral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Antibodies, Neoplasm); 0 (IL31 protein, human); 0 (IL31RA protein, human); 0 (Interleukins); 0 (Receptors, Interleukin); 0 (STAT Transcription Factors); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.10.2 (Janus Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170415
[St] Status:MEDLINE
[do] DOI:10.1189/jlb.3MR0117-033R



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