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  1 / 609 MEDLINE  
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[PMID]:28462525
[Au] Autor:Tummers B; Green DR
[Ad] Endereço:Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
[Ti] Título:Caspase-8: regulating life and death.
[So] Source:Immunol Rev;277(1):76-89, 2017 05.
[Is] ISSN:1600-065X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Roles for cell death in development, homeostasis, and the control of infections and cancer have long been recognized. Although excessive cell damage results in passive necrosis, cells can be triggered to engage molecular programs that result in cell death. Such triggers include cellular stress, oncogenic signals that engage tumor suppressor mechanisms, pathogen insults, and immune mechanisms. The best-known forms of programmed cell death are apoptosis and a recently recognized regulated necrosis termed necroptosis. Of the two best understood pathways of apoptosis, the extrinsic and intrinsic (mitochondrial) pathways, the former is induced by the ligation of death receptors, a subset of the TNF receptor (TNFR) superfamily. Ligation of these death receptors can also induce necroptosis. The extrinsic apoptosis and necroptosis pathways regulate each other and their balance determines whether cells live. Integral in the regulation and initiation of death receptor-mediated activation of programmed cell death is the aspartate-specific cysteine protease (caspase)-8. This review describes the role of caspase-8 in the initiation of extrinsic apoptosis execution and the mechanism by which caspase-8 inhibits necroptosis. The importance of caspase-8 in the development and homeostasis and the way that dysfunctional caspase-8 may contribute to the development of malignancies in mice and humans are also explored.
[Mh] Termos MeSH primário: Caspase 8/imunologia
Inflamassomos/metabolismo
Mitocôndrias/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Mh] Termos MeSH secundário: Animais
Apoptose
Homeostase
Seres Humanos
Necrose
Receptores de Morte Celular/metabolismo
Receptores do Fator de Necrose Tumoral/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Inflammasomes); 0 (Receptors, Death Domain); 0 (Receptors, Tumor Necrosis Factor); 0 (Tumor Necrosis Factor-alpha); EC 3.4.22.- (Caspase 8)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1111/imr.12541


  2 / 609 MEDLINE  
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[PMID]:28460644
[Au] Autor:Teringova E; Tousek P
[Ad] Endereço:Cardiocenter, Department of Cardiology, 3rd Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Srobarova 50, 100 34, Prague 10, Czech Republic.
[Ti] Título:Apoptosis in ischemic heart disease.
[So] Source:J Transl Med;15(1):87, 2017 May 01.
[Is] ISSN:1479-5876
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Apoptosis plays an important role in the myocardial loss after acute myocardial infarction and participates in the process of subsequent left ventricular remodeling and development of symptomatic heart failure. Finding a sensitive apoptotic marker that would help in prognostic stratification of patients after acute myocardial infarction and offer new therapeutic strategies is thus of a great importance. Several studies suggest that tumor necrosis factor-related apoptosis inducing ligand (TRAIL) represents a very promising marker of prognosis in patients with acute myocardial infarction. This review article provides an overview of current knowledge on the role of apoptosis in ischemic heart disease and highlights potentially beneficial apoptotic markers in clinical practice.
[Mh] Termos MeSH primário: Apoptose
Isquemia Miocárdica/patologia
[Mh] Termos MeSH secundário: Biomarcadores/metabolismo
Seres Humanos
Modelos Biológicos
Isquemia Miocárdica/metabolismo
Receptores de Morte Celular/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers); 0 (Receptors, Death Domain)
[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:10.1186/s12967-017-1191-y


  3 / 609 MEDLINE  
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[PMID]:28462521
[Au] Autor:Orozco S; Oberst A
[Ad] Endereço:Department of Immunology, University of Washington, Seattle, WA, USA.
[Ti] Título:RIPK3 in cell death and inflammation: the good, the bad, and the ugly.
[So] Source:Immunol Rev;277(1):102-112, 2017 05.
[Is] ISSN:1600-065X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Necroptosis is a form of cell death that can be observed downstream of death receptor or pattern recognition receptor signaling under certain cellular contexts, or in response to some viral and bacterial infections. The receptor interacting protein kinases-1 (RIPK1) and RIPK3 are at the core of necroptotic signaling, among other proteins. Because this pathway is normally halted by the pro-apoptotic protease caspase-8 and the IAP ubiquitin ligases, how and when necroptosis is triggered in physiological settings are ongoing questions. Interestingly, accumulating evidence suggests that RIPK3 has functions beyond the induction of necroptotic cell death, especially in the areas of tissue injury and sterile inflammation. Here, we will discuss the role of RIPK3 in a variety of physiological conditions, including necroptotic and non-necroptotic cell death, in the context of viral and bacterial infections, tissue damage, and inflammation.
[Mh] Termos MeSH primário: Infecções Bacterianas/imunologia
Inflamação/imunologia
Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
Viroses/imunologia
[Mh] Termos MeSH secundário: Animais
Apoptose
Degradação Necrótica do DNA
Seres Humanos
Necrose
Receptores de Morte Celular/metabolismo
Receptores de Reconhecimento de Padrão/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Receptors, Death Domain); 0 (Receptors, Pattern Recognition); EC 2.7.11.1 (RIPK3 protein, human); EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases)
[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.12536


  4 / 609 MEDLINE  
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[PMID]:28948607
[Au] Autor:Keresztes A; Streicher JM
[Ad] Endereço:Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA.
[Ti] Título:Synergistic interaction of the cannabinoid and death receptor systems - a potential target for future cancer therapies?
[So] Source:FEBS Lett;591(20):3235-3251, 2017 Oct.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cannabinoid receptors have been shown to interact with other receptors, including tumor necrosis factor receptor superfamily (TNFRS) members, to induce cancer cell death. When cannabinoids and death-inducing ligands (including TNF-related apoptosis-inducing ligand) are administered together, they have been shown to synergize and demonstrate enhanced antitumor activity in vitro. Certain cannabinoid ligands have been shown to sensitize cancer cells and synergistically interact with members of the TNFRS, thus suggesting that the combination of cannabinoids with death receptor (DR) ligands induces additive or synergistic tumor cell death. This review summarizes recent findings on the interaction of the cannabinoid and DR systems and suggests possible clinical co-application of cannabinoids and DR ligands in the treatment of various malignancies.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Canabinoides/uso terapêutico
Regulação Neoplásica da Expressão Gênica
Neoplasias/tratamento farmacológico
Receptores de Canabinoides/genética
Receptores de Morte Celular/genética
Ligante Indutor de Apoptose Relacionado a TNF/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Sinergismo Farmacológico
Seres Humanos
Ligantes
Neoplasias/genética
Neoplasias/metabolismo
Neoplasias/patologia
Receptor Cross-Talk
Receptores de Canabinoides/metabolismo
Receptores de Morte Celular/metabolismo
Transdução de Sinais
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cannabinoids); 0 (Ligands); 0 (Receptors, Cannabinoid); 0 (Receptors, Death Domain); 0 (TNF-Related Apoptosis-Inducing Ligand); 0 (TNFSF10 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170927
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12863


  5 / 609 MEDLINE  
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Registro de Ensaios Clínicos
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[PMID]:28427434
[Au] Autor:Schiza A; Wenthe J; Mangsbo S; Eriksson E; Nilsson A; Tötterman TH; Loskog A; Ullenhag G
[Ad] Endereço:Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
[Ti] Título:Adenovirus-mediated CD40L gene transfer increases Teffector/Tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients.
[So] Source:J Transl Med;15(1):79, 2017 04 20.
[Is] ISSN:1479-5876
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND AIMS: Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). METHODS: Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide. Cells were analyzed by flow cytometry while plasma samples were analyzed by a multi-array proteomics. RESULTS: All patients had an increased Teffector/Tregulatory cell ratio post therapy. Simultaneously, the death receptors TNFR1 and TRAIL-R2 were significantly up-regulated post treatment. Stem cell factor (SCF), E-selectin, and CD6 correlated to enhanced overall survival while a high level of granulocytic myeloid-derived suppressor cells (gMDSCs), IL8, IL10, TGFb1, CCL4, PlGF and Fl3t ligand was highest in patients with short survival. CONCLUSIONS: AdCD40L intratumoral injection induced desirable systemic immune effects that correlated to prolonged survival. Further studies using CD40 stimulation in malignant melanoma are warranted. Trial registration The 002:CD40L trial "Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors" (clinicalTrials.gov identifier: NCT01455259) was registered at September 2011.
[Mh] Termos MeSH primário: Adenoviridae/metabolismo
Ligante de CD40/genética
Técnicas de Transferência de Genes
Melanoma/imunologia
Melanoma/secundário
Receptores de Morte Celular/metabolismo
Linfócitos T Reguladores/imunologia
Regulação para Cima
[Mh] Termos MeSH secundário: Antígenos CD/metabolismo
Antígenos de Diferenciação de Linfócitos T/metabolismo
Seres Humanos
Contagem de Linfócitos
Melanoma/sangue
Melanoma/terapia
Células Supressoras Mieloides/imunologia
Proteômica
Fator de Células-Tronco/metabolismo
Análise de Sobrevida
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Antigens, Differentiation, T-Lymphocyte); 0 (CD6 antigen); 0 (Receptors, Death Domain); 0 (Stem Cell Factor); 147205-72-9 (CD40 Ligand)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1186/s12967-017-1182-z


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[PMID]:28350813
[Au] Autor:González R; De la Rosa ÁJ; Rufini A; Rodríguez-Hernández MA; Navarro-Villarán E; Marchal T; Pereira S; De la Mata M; Müller-Schilling M; Pascasio-Acevedo JM; Ferrer-Ríos MT; Gómez-Bravo MA; Padillo FJ; Muntané J
[Ad] Endereço:Institute of Biomedicine of Seville (IBiS), Hospital University "Virgen del Rocío"/IBiS/CSIC/University of Seville, Seville, Spain.
[Ti] Título:Role of p63 and p73 isoforms on the cell death in patients with hepatocellular carcinoma submitted to orthotopic liver transplantation.
[So] Source:PLoS One;12(3):e0174326, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND & AIMS: Patients with hepatocellular carcinoma (HCC) submitted to orthotopic liver transplantation (OLT) have a variable 5-year survival rate limited mostly by tumor recurrence. The etiology, age, sex, alcohol, Child-Pugh, and the immunesuppressor have been associated with tumour recurrence. The expression of ΔNp73 is related to the reduced survival of patients with HCC. The study evaluated the expression of p63 and p73 isoforms and cell death receptors, and their relation to tumour recurrence and survival. The results were in vitro validated in HCC cell lines. METHODS: HCC sections from patients submitted to OLT were used. The in vitro study was done in differentiated hepatitis B virus (HBV)-expressing Hep3B and control HepG2 cells. The expression of cell death receptors and cFLIPS/L, caspase-8 and -3 activities, and cell proliferation were determined in control and p63 and p73 overexpressing HCC cells. RESULTS: The reduced tumor expression of cell death receptors and TAp63 and TAp73, and increased ΔNp63 and ΔNp73 expression were associated with tumor recurrence and reduced survival. The in vitro study demonstrated that HBV-expressing Hep3B vs HepG2 cells showed reduced expression of p63 and p73, cell death receptors and caspase activation, and increased cFLIPL/cFLIPS ratio. The overexpression of TAp63 and TAp73 exerted a more potent pro-apoptotic and anti-proliferative effects in Hep3B than HepG2-transfected cells which was related to cFLIPL upregulation. CONCLUSIONS: The reduction of TAp63 and TAp73 isoforms, rather than alteration of ΔN isoform expression, exerted a significant functional repercussion on cell death and proliferation in HBV-expressing HepB cells.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/terapia
Neoplasias Hepáticas/terapia
Transplante de Fígado
Fígado/patologia
Fatores de Transcrição/genética
Proteína Tumoral p73/genética
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Carcinoma Hepatocelular/genética
Carcinoma Hepatocelular/patologia
Carcinoma Hepatocelular/virologia
Morte Celular
Linhagem Celular Tumoral
Feminino
Regulação Neoplásica da Expressão Gênica
Hepatite B/complicações
Vírus da Hepatite B/isolamento & purificação
Seres Humanos
Fígado/metabolismo
Fígado/virologia
Neoplasias Hepáticas/genética
Neoplasias Hepáticas/patologia
Neoplasias Hepáticas/virologia
Transplante de Fígado/métodos
Masculino
Isoformas de Proteínas/genética
Receptores de Morte Celular/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Isoforms); 0 (Receptors, Death Domain); 0 (TP63 protein, human); 0 (Transcription Factors); 0 (Tumor Protein p73); 0 (Tumor Suppressor Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170329
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0174326


  7 / 609 MEDLINE  
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[PMID]:28177892
[Au] Autor:Paiva C; Godbersen JC; Rowland T; Danilova OV; Danes C; Berger A; Danilov AV
[Ad] Endereço:Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
[Ti] Título:Pevonedistat, a Nedd8-activating enzyme inhibitor, sensitizes neoplastic B-cells to death receptor-mediated apoptosis.
[So] Source:Oncotarget;8(13):21128-21139, 2017 Mar 28.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:While death receptor ligands (Fas and TRAIL) kill chemoresistant tumor cell lines, related therapies have limited clinical efficacy as single agents. Death receptor signaling is modulated by nuclear factor-κB (NFκB), a family of transcription factors which are constitutively active in B-cell malignancies. We and others have shown that pevonedistat, an investigational inhibitor of the NEDD8-activating enzyme, abrogates NFκB activity in B-cell neoplasia. Here we demonstrate that diffuse large B-cell lymphoma, particularly activated B-cell type, and primary chronic lymphocytic leukemia cells are re-sensitized to extrinsic apoptosis by pevonedistat. Pevonedistat enhanced caspase-8 processing following death receptor ligation, and downmodulated cFLIP, a NFκB-regulated protease-deficient caspase homolog. However, treatment with pevonedistat did not modulate death-inducing signaling complex in neoplastic B-cells, suggesting that they were sensitized to death ligands through the mitochondrial pathway. Our data provide rationale for further development of pharmacologic agents including pevonedistat in strategies which enhance death receptor signaling in lymphoid malignancies.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Linfócitos B/efeitos dos fármacos
Ciclopentanos/farmacologia
Inibidores Enzimáticos/farmacologia
Linfoma Difuso de Grandes Células B/patologia
Pirimidinas/farmacologia
[Mh] Termos MeSH secundário: Linfócitos B/metabolismo
Seres Humanos
Immunoblotting
Imunoprecipitação
Proteína NEDD8
Receptores de Morte Celular/metabolismo
Ubiquitinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cyclopentanes); 0 (Enzyme Inhibitors); 0 (NEDD8 Protein); 0 (NEDD8 protein, human); 0 (Pyrimidines); 0 (Receptors, Death Domain); 0 (Ubiquitins); S3AZD8D215 (pevonedistat)
[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:170209
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15050


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[PMID]:27762484
[Au] Autor:Liu X; Ding S; Shi P; Dietrich R; Märtlbauer E; Zhu K
[Ad] Endereço:Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
[Ti] Título:Non-hemolytic enterotoxin of Bacillus cereus induces apoptosis in Vero cells.
[So] Source:Cell Microbiol;19(4), 2017 Apr.
[Is] ISSN:1462-5822
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Bacillus cereus is an opportunistic pathogen that often causes foodborne infectious diseases and food poisoning. Non-hemolytic enterotoxin (Nhe) is the major toxin found in almost all enteropathogenic B. cereus and B. thuringiensis isolates. However, little is known about the cellular response after Nhe triggered pore formation on cell membrane. Here, we demonstrate that Nhe induced cell cycle arrest at G /G phase and provoked apoptosis in Vero cells, most likely associated with mitogen-activated protein kinase (MAPK) and death receptor pathways. The influx of extracellular calcium ions and increased level of reactive oxygen species in cytoplasm were sensed by apoptosis signal-regulating kinase 1 (ASK1) and p38 MAPK. Extrinsic death receptor Fas could also promote the activation of p38 MAPK. Subsequently, ASK1 and p38 MAPK triggered downstream caspase-8 and 3 to initiate apoptosis. Our results clearly demonstrate that ASK1, and Fas-p38 MAPK-mediated caspase-8 dependent pathways are involved in apoptotic cell death provoked by the pore-forming enterotoxin Nhe.
[Mh] Termos MeSH primário: Apoptose/imunologia
Bacillus cereus/fisiologia
Enterotoxinas/fisiologia
[Mh] Termos MeSH secundário: Animais
Toxinas Bacterianas/farmacologia
Sinalização do Cálcio
Cercopithecus aethiops
Enterotoxinas/farmacologia
Pontos de Checagem da Fase G1 do Ciclo Celular
Estresse Oxidativo
Receptores de Morte Celular/metabolismo
Transdução de Sinais
Células Vero
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Toxins); 0 (Enterotoxins); 0 (Receptors, Death Domain)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170724
[Lr] Data última revisão:
170724
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161021
[St] Status:MEDLINE
[do] DOI:10.1111/cmi.12684


  9 / 609 MEDLINE  
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[PMID]:27113412
[Au] Autor:Li CC; Yu FS; Fan MJ; Chen YY; Lien JC; Chou YC; Lu HF; Tang NY; Peng SF; Huang WW; Chung JG
[Ad] Endereço:Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, 404.
[Ti] Título:Anticancer effects of cantharidin in A431 human skin cancer (Epidermoid carcinoma) cells in vitro and in vivo.
[So] Source:Environ Toxicol;32(3):723-738, 2017 Mar.
[Is] ISSN:1522-7278
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cantharidin (CTD), a potential anticancer agent of Traditional Chinese Medicine has cytotxic effects in different human cancer cell lines. The cytotoxic effects of CTD on A431 human skin cancer (epidermoid carcinoma) cells in vitro and in A431 cell xenograft mouse model were examined. In vitro, A431 human skin cell were treated with CTD for 24 and 48 h. Cell phase distribution, ROS production, Ca release, Caspase activity and the level of apoptosis associated proteins were measured. In vivo, A431 cell xenograft mouse model were examined. CTD-induced cell morphological changes and decreased percentage of viable A431 cells via G0/G1 phase arrest and induced apoptosis. CTD-induced G0/G1 phase arrest through the reduction of protein levels of cyclin E, CDK6, and cyclin D in A431 cells. CTD-induced cell apoptosis of A431 cells also was confirm by DNA gel electrophoresis showed CTD-induced DNA fragmentation. CTD reduced the mitochondrial membrane potential and stimulated release of cytochrome c, AIF and Endo G in A431 cells. Flow cytometry demonstrated that CTD increased activity of caspase-8, -9 and -3. However, when cells were pretreated with specific caspase inhibitors activity was reduced and cell viability increased. CTD increased protein levels of death receptors such as DR4, DR5, TRAIL and levels of the active form of caspase-8, -9 and -3 in A431 cells. AIF and Endo G proteins levels were also enhanced by CTD. In vivo studies showed that CTD significantly inhibited A431 cell xenograft tumors in mice. Taken together, these in vitro and in vivo results provide insight into the mechanisms of CTD on cell growth and tumor production. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 723-738, 2017.
[Mh] Termos MeSH primário: Antineoplásicos/toxicidade
Apoptose/efeitos dos fármacos
Cantaridina/toxicidade
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/uso terapêutico
Cantaridina/uso terapêutico
Carcinoma de Células Escamosas/tratamento farmacológico
Carcinoma de Células Escamosas/metabolismo
Carcinoma de Células Escamosas/patologia
Caspases/genética
Caspases/metabolismo
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Ciclina D/metabolismo
Citocromos c/metabolismo
Fragmentação do DNA/efeitos dos fármacos
Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos
Seres Humanos
Masculino
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Espécies Reativas de Oxigênio/metabolismo
Receptores de Morte Celular/metabolismo
Transdução de Sinais/efeitos dos fármacos
Neoplasias Cutâneas/tratamento farmacológico
Neoplasias Cutâneas/metabolismo
Neoplasias Cutâneas/patologia
Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
Transplante Heterólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cyclin D); 0 (Reactive Oxygen Species); 0 (Receptors, Death Domain); 0 (TNF-Related Apoptosis-Inducing Ligand); 9007-43-6 (Cytochromes c); EC 3.4.22.- (Caspases); IGL471WQ8P (Cantharidin)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170322
[Lr] Data última revisão:
170322
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160427
[St] Status:MEDLINE
[do] DOI:10.1002/tox.22273


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[PMID]:27685624
[Au] Autor:Dominguez C; Tsang KY; Palena C
[Ad] Endereço:Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
[Ti] Título:Short-term EGFR blockade enhances immune-mediated cytotoxicity of EGFR mutant lung cancer cells: rationale for combination therapies.
[So] Source:Cell Death Dis;7(9):e2380, 2016 Sep 29.
[Is] ISSN:2041-4889
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) erlotinib has been approved for years as a first-line therapy for patients harboring EGFR-sensitizing mutations. With the promising implementation of immunotherapeutic strategies for the treatment of lung cancer, there is a growing interest in developing combinatorial therapies that could utilize immune approaches in the context of conventional or targeted therapies. Tumor cells are known to evade immune attack by multiple strategies, including undergoing phenotypic plasticity via a process designated as the epithelial-mesenchymal transition (EMT). As signaling through EGFR is a major inducer of EMT in epithelial cells, we have investigated the effect of EGFR inhibition with erlotinib on tumor phenotype and susceptibility to immune attack. Our data shows that short-term exposure of tumor cells to low-dose erlotinib modulates tumor plasticity and immune-mediated cytotoxicity in lung cancer cells harboring a sensitizing EGFR mutation, leading to a remarkable enhancement of tumor lysis mediated by innate NK cells and antigen-specific T cells. This effect positively correlated with the ability of short-term EGFR blockade to modulate tumor phenotype towards a more epithelial one, as well as to increase susceptibility to caspase-mediated apoptosis. The effect, however, was lost when erlotinib was utilized for long periods of time in vitro or in vivo, which resulted in gain of mesenchymal features and decreased (rather than increased) tumor lysis in response to immune effector mechanisms. Our data provides rationale for potential combinations of erlotinib and immunotherapies for the treatment of lung carcinomas in the early setting, before the establishment of tumor relapse with long-term EGFR inhibition.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Citotoxicidade Imunológica
Neoplasias Pulmonares/tratamento farmacológico
Neoplasias Pulmonares/imunologia
Mutação/genética
Receptor do Fator de Crescimento Epidérmico/antagonistas & inibidores
[Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Apoptose/efeitos dos fármacos
Biomarcadores Tumorais/metabolismo
Carcinoma Pulmonar de Células não Pequenas/genética
Carcinoma Pulmonar de Células não Pequenas/imunologia
Carcinoma Pulmonar de Células não Pequenas/patologia
Caspases/metabolismo
Linhagem Celular Tumoral
Citotoxicidade Imunológica/efeitos dos fármacos
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Transição Epitelial-Mesenquimal/efeitos dos fármacos
Cloridrato de Erlotinib/farmacologia
Cloridrato de Erlotinib/uso terapêutico
Seres Humanos
Interleucina-8/metabolismo
Neoplasias Pulmonares/genética
Fenótipo
Receptor do Fator de Crescimento Epidérmico/metabolismo
Receptores de Morte Celular/metabolismo
Transdução de Sinais/efeitos dos fármacos
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Interleukin-8); 0 (Receptors, Death Domain); DA87705X9K (Erlotinib Hydrochloride); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160930
[St] Status:MEDLINE
[do] DOI:10.1038/cddis.2016.297



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