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[PMID]:29429158
[Au] Autor:Sun M; Liu JG; Weng QY; Yu L; Wang J
[Ad] Endereço:Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
[Ti] Título:[Pleomorphic and dedifferentiated leiomyosarcoma: a clinicopathologic analysis].
[So] Source:Zhonghua Bing Li Xue Za Zhi;47(2):87-93, 2018 Feb 08.
[Is] ISSN:0529-5807
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To investigate the clinicopathologic features, differential diagnosis and biological behavior of pleomorphic leiomyosarcoma (PLMS) and dedifferentiated leiomyosarcoma (DLMS). Forty-nine cases were collected from November 2007 to December 2016, including eight that diagnosed at Fudan University Shanghai Cancer Center, and 41 consultation cases. The clinical findings and pathologic features were reviewed. Immunophenotype was obtained in 33 cases and follow-up information was available in 38 cases. There were 22 males and 27 females with ages ranging from 24 to 83 years (mean 52.5 years). Fifteen cases occurred in extremities, 14 in deep body cavity, 11 in the trunk, 4 in the head and neck, 2 in the bladder, and 1 each in the inguinal region, perineum and femoral vein, respectively. Tumor sizes ranged from 3 to 30 cm (mean 9.1 cm). The tumors were composed of at least small foci of typical leiomyosarcoma (LMS) and areas of high-grade pleomorphic/undifferentiated sarcoma. The typical LMS component showed the characteristic morphology of smooth muscle differentiation and was low to intermediate grade in most cases. Pleomorphic areas were mainly composed of atypical spindle and polygonal cells admixed with variable large, bizarre atypical cells and multinuclear giant cells, mostly mimicking undifferentiated pleomorphic sarcoma. The pleomorphic and leiomyosarcomatous areas were usually intermixed, but the demarcation may be distinct or gradual in some cases. The classical LMS component was positive for at least one myogenic marker: α-SMA in 97.0%(32/33), desmin in 72.7%(24/33), H-caldesmon in 90.9% (20/22), MSA in 14/16, and calponin in 15/15 of cases. The pleomorphic sarcoma component was reactive for at least one myogenic marker in 87.9% (29/33) of cases, usually showing focal and less intense immunoreactivity than classical LMS component: α-SMA was positive in 81.8%(27/33), desmin in 48.5%(16/33), H-caldesmon in 72.7% (16/22), MSA in 12/16, and calponin in 11/15 of cases. Based on staining for muscle markers in the pleomorphic component, 29 cases were designated as PLMS, 4 as DLMS. Ki-67 index ranged from 15% to 70% (mean 40%). Follow-up data was available in 38 cases (77.6%), of which 11 patients (28.9%) died of disease, 12 patients were alive with unresectable or recurrent disease, 14 patients were alive with no evidence of disease and another one died of unrelated cause. The median disease-free and overall survival was 6 and 10 months respectively. Twelve patients exhibited local recurrence and 11 developed metastases. The median interval to progression was 8 months. The identification of areas of typical LMS is crucial for accurate diagnosis of PLMS and DLMS. Both PLMS and DLMS show more aggressive behavior and poorer prognosis than ordinary LMS.
[Mh] Termos MeSH primário: Leiomiossarcoma/patologia
Neoplasias Cutâneas/patologia
[Mh] Termos MeSH secundário: Actinas/análise
Adulto
Idoso
Idoso de 80 Anos ou mais
Biomarcadores Tumorais/análise
Proteínas de Ligação ao Cálcio/análise
Proteínas de Ligação a Calmodulina/análise
Diferenciação Celular
China
Desmina/análise
Diagnóstico Diferencial
Extremidades
Feminino
Histiocitoma Fibroso Maligno/química
Histiocitoma Fibroso Maligno/patologia
Seres Humanos
Imuno-Histoquímica
Imunofenotipagem
Leiomiossarcoma/química
Masculino
Proteínas dos Microfilamentos/análise
Meia-Idade
Recidiva Local de Neoplasia
Neoplasias Cutâneas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ACTA2 protein, human); 0 (Actins); 0 (Biomarkers, Tumor); 0 (Calcium-Binding Proteins); 0 (Calmodulin-Binding Proteins); 0 (Desmin); 0 (Microfilament Proteins); 0 (calponin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0529-5807.2018.02.002


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[PMID]:29340527
[Au] Autor:Ribeiro LP; Freitas-Lima LC; Naumann GB; Meyrelles SS; Lunz W; Pires SF; Andrade HM; Carnielli JBT; Figueiredo SG
[Ad] Endereço:Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
[Ti] Título:Cardiac protein expression patterns are associated with distinct inborn exercise capacity in non-selectively bred rats.
[So] Source:Braz J Med Biol Res;51(3):e7033, 2018 Jan 11.
[Is] ISSN:1414-431X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:In the present study, we successfully demonstrated for the first time the existence of cardiac proteomic differences between non-selectively bred rats with distinct intrinsic exercise capacities. A proteomic approach based on two-dimensional gel electrophoresis coupled to mass spectrometry was used to study the left ventricle (LV) tissue proteome of rats with distinct intrinsic exercise capacity. Low running performance (LRP) and high running performance (HRP) rats were categorized by a treadmill exercise test, according to distance run to exhaustion. The running capacity of HRPs was 3.5-fold greater than LRPs. Protein profiling revealed 29 differences between HRP and LRP rats (15 proteins were identified). We detected alterations in components involved in metabolism, antioxidant and stress response, microfibrillar and cytoskeletal proteins. Contractile proteins were upregulated in the LVs of HRP rats (α-myosin heavy chain-6, myosin light chain-1 and creatine kinase), whereas the LVs of LRP rats exhibited upregulation in proteins associated with stress response (aldehyde dehydrogenase 2, α-crystallin B chain and HSPß-2). In addition, the cytoskeletal proteins desmin and α-actin were upregulated in LRPs. Taken together, our results suggest that the increased contractile protein levels in HRP rats partly accounted for their improved exercise capacity, and that proteins considered risk factors to the development of cardiovascular disease were expressed in higher amounts in LRP animals.
[Mh] Termos MeSH primário: Testes de Função Cardíaca/métodos
Miocárdio/metabolismo
Condicionamento Físico Animal/fisiologia
Proteínas/metabolismo
Corrida/fisiologia
[Mh] Termos MeSH secundário: Animais
Proteínas Contráteis/metabolismo
Proteínas do Citoesqueleto/metabolismo
Desmina/metabolismo
Eletroforese em Gel Bidimensional
Ventrículos do Coração/metabolismo
Proteínas de Choque Térmico/metabolismo
Masculino
Espectrometria de Massas
Tamanho do Órgão
Proteínas/isolamento & purificação
Proteômica
Ratos
Ratos Endogâmicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Contractile Proteins); 0 (Cytoskeletal Proteins); 0 (Desmin); 0 (Heat-Shock Proteins); 0 (Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


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[PMID]:29325250
[Au] Autor:Fu Y; Guan WY; Wu HY; Wu HY; Fan ZW; Ye Q; Meng FQ
[Ad] Endereço:Department of Pathology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
[Ti] Título:[Myofibroma/myofibromatosis: a clinicopathologic analysis of 9 cases].
[So] Source:Zhonghua Bing Li Xue Za Zhi;47(1):45-50, 2018 Jan 08.
[Is] ISSN:0529-5807
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To investigate the clinical and histological features, diagnosis and differential diagnosis of myofibroma/myofibromatosis. The clinical data and pathology features of nine cases of myofibroma/myofibromatosis were collected from August 2011 to November 2016 in Affiliated Drum Tower Hospital, Nanjing University Medical School and Children's Hospital of Nanjing Medical University. Immunohistochemistry(IHC), PDGFRB molecular analysis and ETV6-NTRK3 gene fusion were performed and relevant literature reviewed. There were 7 males and 2 females, with age ranging from 3 days to 18 years (mean 5 years). The tumors were located in head and neck (eight cases) and trunk (one case). Clinically, the tumors presented as freely movable nodules. Microscopically, they appeared biphasic with alternating light- and dark-staining areas. The light-staining area consisted mainly of plump myoid spindle cells with eosinophilic cytoplasm arranged in nodules, short fascicles, or whorls.The dark-staining area was composed of round or polygonal cells with slightly hyperchromatic nuclei or small spindle cells arranged around a distinct hemangiopericytoma-like vascular pattern. IHC showed the tumor cells in the light-staining area were strongly positive for vimentin and SMA, while cells in dark-staining area were strongly positive for vimentin, and weakly for SMA. Tumor cells were negative for desmin, S-100 protein, h-Caldesmon, CD34 and STAT6. Analysis of PDGFRB mutations was performed in seven cases. Two cases showed 12 exon point mutation c. 1681 c>T(p.R561C), one case showed 14 exon point mutation c. 1998C>G (p.N666K). ETV6-NTRK3 gene fusion was not detected by fluorescence in situ hybridization in four patients under three years old. All cases were followed for 6 to 68 months, with two recurrences. Myofibroma/myofibromatosis is an uncommon benign myofibroblastic tumor of infancy and childhood. The tumor can appear biphasic, and may show PDGFRB point mutation which is of potential diagnostic value.
[Mh] Termos MeSH primário: Miofibroma
Miofibromatose
[Mh] Termos MeSH secundário: Adolescente
Antígenos CD34/análise
Proteínas de Ligação a Calmodulina/análise
Criança
Pré-Escolar
Desmina/análise
Diagnóstico Diferencial
Éxons
Feminino
Hemangiopericitoma/irrigação sanguínea
Seres Humanos
Imuno-Histoquímica
Hibridização in Situ Fluorescente
Masculino
Mutação
Miofibroma/diagnóstico
Miofibroma/genética
Miofibroma/patologia
Miofibromatose/diagnóstico
Miofibromatose/genética
Miofibromatose/patologia
Receptor beta de Fator de Crescimento Derivado de Plaquetas/análise
Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética
Proteínas S100/análise
Fator de Transcrição STAT6/análise
Vimentina/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD34); 0 (Calmodulin-Binding Proteins); 0 (Desmin); 0 (S100 Proteins); 0 (STAT6 Transcription Factor); 0 (STAT6 protein, human); 0 (Vimentin); EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0529-5807.2018.01.009


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[PMID]:29224278
[Au] Autor:Zhao M; LaoI QY; Zhao DH; Ma J; Ru GQ; He XL; Wang Z; Wang J
[Ad] Endereço:Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
[Ti] Título:[Clinicopathologic and molecular genetic characterizations of biphenotypic sinonasal sarcoma].
[So] Source:Zhonghua Bing Li Xue Za Zhi;46(12):841-846, 2017 Dec 08.
[Is] ISSN:0529-5807
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To investigate the clinicopathologic characteristics, immunophenotypes, molecular genetics, and diagnostic and differential diagnostic features of biphenotypic sinonasal sarcoma (BSNS). Three cases of BSNS were retrieved, the histomorphology, immunophenotype and molecular genetics were analyzed with review of literature. There were 2 male and 1 female patient aged 45, 29 and 40 years, respectively.Computed tomography and magnetic resonance imaging examinations showed a large polypoid mass occupying the sinonasal cavity in all 3 patients. Microscopically, these tumors were un-circumscribed and composed of cellular spindle-shaped cells arranged in long and interlaced fascicles. A hemangiopericytoma-like growth pattern was frequently identified. The overlying hyperplastic respiratory epithelium invaginated down into the tumor forming a cystic (2 cases), glandular (1 case) structures and inverted in a papilloma-like (1 case)pattern, and foci of eosinophilic metaplasia were also noted in 2 of the three cases. The tumor nuclei were bland-appearing, mitoses were scarce and necrosis was absent. Immunohistochemically, the tumor cells showed co-expression of neural and myogenic markers in all the 3 cases, including that 3/3 showed diffuse and strong positivity of S-100 protein, 3/3 positivity of smooth muscle actin (1 diffuse and 2 focal), 1/2 diffuse positivity of calponin, 1/3 focal positivity of desmin, and 1/1 focal positivity of MyoD1.In addition, 1 detected for ß-catenin showed focal nuclear positivity. None of the 3 showed positivity to cytokeratin, CD34 or SOX10 in the tumor cells.Ki-67 showed an index <5%, 10% and <2%, respectively. Fluorescence in situ hybridization analysis showed rearrangements of PAX3 gene in all 3 cases. In case 3, reverse transcription polymerase chain reaction, followed by Sanger sequencing, demonstrated an in-frame fusion between PAX3 and FOXO1.Follow-up information (range 3-15 months)showed no evidence of local recurrence or distant metastasis in three cases. BSNS is a newly described entity which can be readily confused with a variety of benign and malignant spindle cell tumors encountered in the sinonasal cavity; immunohistochemistry co-expression of neural and myogenic markers and PAX3 gene rearrangement can help distinguish this tumor from its many mimickers.
[Mh] Termos MeSH primário: Neoplasias dos Seios Paranasais/genética
Neoplasias dos Seios Paranasais/patologia
Sarcoma/genética
Sarcoma/patologia
[Mh] Termos MeSH secundário: Adulto
Biomarcadores Tumorais/análise
Núcleo Celular
Desmina/análise
Diagnóstico Diferencial
Feminino
Rearranjo Gênico
Hemangiopericitoma/patologia
Seres Humanos
Imuno-Histoquímica
Imunofenotipagem
Hibridização in Situ Fluorescente
Queratinas/análise
Masculino
Meia-Idade
Recidiva Local de Neoplasia
Fator de Transcrição PAX3/genética
Neoplasias dos Seios Paranasais/química
Neoplasias dos Seios Paranasais/imunologia
Proteínas S100/análise
Fatores de Transcrição SOXE/análise
Sarcoma/química
Sarcoma/imunologia
beta Catenina/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (CTNNB1 protein, human); 0 (Desmin); 0 (PAX3 Transcription Factor); 0 (PAX3 protein, human); 0 (S100 Proteins); 0 (SOXE Transcription Factors); 0 (beta Catenin); 68238-35-7 (Keratins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0529-5807.2017.12.006


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[PMID]:28793217
[Au] Autor:Even C; Abramovici G; Delort F; Rigato AF; Bailleux V; de Sousa Moreira A; Vicart P; Rico F; Batonnet-Pichon S; Briki F
[Ad] Endereço:Laboratoire de Physique des Solides, CNRS, Université Paris Sud, Université Paris-Saclay, Orsay, France. Electronic address: catherine.even@u-psud.fr.
[Ti] Título:Mutation in the Core Structure of Desmin Intermediate Filaments Affects Myoblast Elasticity.
[So] Source:Biophys J;113(3):627-636, 2017 Aug 08.
[Is] ISSN:1542-0086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Elastic properties of cells are mainly derived from the actin cytoskeleton. However, intermediate filaments are emerging as major contributors to the mechanical properties of cells. Using atomic force microscopy, we studied the elasticity of mouse myoblasts expressing a mutant form of the gene encoding for desmin intermediate filaments, p.D399Y. This variant produces desmin aggregates, the main pathological symptom of myofibrillar myopathies. Here we show that desmin-mutated cells display a 39% increased median elastic modulus compared to wild-type cells. Desmin-mutated cells required higher forces than wild-type cells to reach high indentation depths, where desmin intermediate filaments are typically located. In addition, heat-shock treatment increased the proportion of cells with aggregates and induced a secondary peak in the distribution of Young's moduli. By performing atomic force microscopy mechanical mapping combined with fluorescence microscopy, we show that higher Young's moduli were measured where desmin aggregates were located, indicating that desmin aggregates are rigid. Therefore, we provide evidence that p.D399Y stiffens mouse myoblasts. Based on these results, we suggest that p.D399Y-related myofibrillar myopathy is at least partly due to altered mechanical properties at the single-cell scale, which are propagated to the tissue scale.
[Mh] Termos MeSH primário: Desmina/química
Desmina/metabolismo
Elasticidade
Filamentos Intermediários/metabolismo
Mutação
Mioblastos/citologia
[Mh] Termos MeSH secundário: Linhagem Celular
Desmina/genética
Seres Humanos
Agregados Proteicos
Domínios Proteicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Desmin); 0 (Protein Aggregates)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE


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[PMID]:28719898
[Au] Autor:Lin X; Zhen X; Huang H; Wu H; You Y; Guo P; Gu X; Yang F
[Ti] Título:Role of MiR-155 Signal Pathway in Regulating Podocyte Injury Induced by TGF-ß1.
[So] Source:Cell Physiol Biochem;42(4):1469-1480, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Transforming growth factor beta 1 (TGF-ß1) plays a critical role in the pathogenesis of glomerulosclerosis. The purpose of this study was to examine the effects of inhibition of miR-155 on podocyte injury induced by TGF-ß1 and to determine further molecular mediators involved in the effects of miR-155. METHODS: Conditionally immortalized podocytes were cultured in vitro and they were divided into four groups: control; TGF-ß1 treatment; TGF-ß1 with miR-155 knockdown [using antisense oligonucleotides against miR-155 (ASO-miR-155)] and TGF-ß1 with negative control antisense oligonucleotides (ASO-NC). Real time RT-PCR and Western blot analysis were employed to determine the mRNA and protein expression of nephrin, desmin and caspase-9, respectively. Flow cytometry was used to examine the apoptotic rate of podocytes and DAPI fluorescent staining was used to determine apoptotic morphology. In addition, we examined the levels of miR-155, TGF-ß1, nephrin, desmin and caspase-9 in glomerular tissues of nephropathy induced by intravenous injections of adriamycin in rats. RESULTS: mRNA and protein expression of desmin and caspase-9 was increased in cultured TGF-ß1-treated podocytes, whereas nephrin was decreased as compared with the control group. Importantly, miR-155 knockdown significantly attenuated upregulation of desmin and caspase-9, and alleviated impairment of nephrin induced by TGF-ß1. Moreover, the number of apoptotic podocytes was increased after exposure to TGF-ß1 and this was alleviated after miR-155 knockdown. Knocking down miR-155 also decreased an apoptosis rate of TGF-ß1-treated podocytes. Note that negative control antisense oligonucleotides failed to alter an increase of the apoptosis rate in TGF-ß1-treated podocytes. Consistent with in vitro results, expression of miR-155, TGF-ß1, desmin and caspase-9 was increased and nephrin was decreased in glomerular tissues with nephropathy in vivo experiments. CONCLUSIONS: TGF-ß1 impairs the protein expression of nephrin and amplifies the protein expression of desmin and caspase -9 via miR-155 signal pathway. Inhibition of miR-155 alleviates these changes in podocytes-treated with TGF-ß1 and attenuated apoptosis of podocytes. Our data suggest that miR-155 plays a role in mediating TGF-ß1-induced podocyte injury via nephrin, desmin and caspase-9. Results of the current study also indicate that blocking miR-155 signal has a protective effect on podocyte injury. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of podocyte injury observed in glomerulosclerosis.
[Mh] Termos MeSH primário: Caspase 9/genética
Desmina/genética
Glomerulosclerose Segmentar e Focal/genética
Proteínas de Membrana/genética
MicroRNAs/genética
Podócitos/efeitos dos fármacos
Fator de Crescimento Transformador beta1/farmacologia
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Apoptose/genética
Caspase 9/metabolismo
Linhagem Celular Transformada
Desmina/metabolismo
Doxorrubicina
Regulação da Expressão Gênica
Glomerulosclerose Segmentar e Focal/induzido quimicamente
Glomerulosclerose Segmentar e Focal/metabolismo
Glomerulosclerose Segmentar e Focal/patologia
Masculino
Proteínas de Membrana/metabolismo
MicroRNAs/antagonistas & inibidores
MicroRNAs/metabolismo
Oligorribonucleotídeos Antissenso/genética
Oligorribonucleotídeos Antissenso/metabolismo
Podócitos/metabolismo
Podócitos/patologia
Ratos
Ratos Sprague-Dawley
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Desmin); 0 (MIRN155 microRNA, rat); 0 (Membrane Proteins); 0 (MicroRNAs); 0 (Oligoribonucleotides, Antisense); 0 (Transforming Growth Factor beta1); 0 (nephrin); 80168379AG (Doxorubicin); EC 3.4.22.- (Casp9 protein, rat); EC 3.4.22.- (Caspase 9)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.1159/000479211


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[PMID]:28655832
[Au] Autor:McLendon PM; Davis G; Gulick J; Singh SR; Xu N; Salomonis N; Molkentin JD; Robbins J
[Ad] Endereço:From the Division of Molecular Cardiovascular Biology, Heart Institute, Cincinnati Children's Hospital Medical Center, OH (P.M.M., G.D., J.G., S.R.S., N.X., J.D.M., J.R.); Division of Biomedical Informatics, Cincinnati Children's Hospital, OH (N.S.); and UES, Inc, Dayton, OH (P.M.M.).
[Ti] Título:An Unbiased High-Throughput Screen to Identify Novel Effectors That Impact on Cardiomyocyte Aggregate Levels.
[So] Source:Circ Res;121(6):604-616, 2017 Sep 01.
[Is] ISSN:1524-4571
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Postmitotic cells, such as cardiomyocytes, seem to be particularly susceptible to proteotoxic stimuli, and large, proteinaceous deposits are characteristic of the desmin-related cardiomyopathies and crystallin cardiomyopathic diseases. Increased activity of protein clearance pathways in the cardiomyocyte, such as proteasomal degradation and autophagy, has proven to be beneficial in maintaining cellular and cardiac function in the face of multiple proteotoxic insults, holding open the possibility of targeting these processes for the development of effective therapeutics. OBJECTIVE: Here, we undertake an unbiased, total genome screen for RNA transcripts and their protein products that affect aggregate accumulations in the cardiomyocytes. METHODS AND RESULTS: Primary mouse cardiomyocytes that accumulate aggregates as a result of a mutant CryAB (αB-crystallin) causative for human desmin-related cardiomyopathy were used for a total genome-wide screen to identify gene products that affected aggregate formation. We infected cardiomyocytes using a short hairpin RNA lentivirus library in which the mouse genome was represented. The screen identified multiple candidates in many cell signaling pathways that were able to mediate significant decreases in aggregate levels. CONCLUSIONS: Subsequent validation of one of these candidates, Jak1 (Janus kinase 1), a tyrosine kinase of the nonreceptor type, confirmed the usefulness of this approach in identifying previously unsuspected players in proteotoxic processes.
[Mh] Termos MeSH primário: Cardiomiopatias/genética
Clonagem Molecular/métodos
Cristalinas/genética
Desmina/genética
Ensaios de Triagem em Larga Escala/métodos
Miócitos Cardíacos/metabolismo
Transcriptoma
[Mh] Termos MeSH secundário: Animais
Agregação Celular/genética
Células Cultivadas
Janus Quinase 1/genética
Janus Quinase 1/metabolismo
Camundongos
Miócitos Cardíacos/fisiologia
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Crystallins); 0 (Desmin); EC 2.7.10.2 (Janus Kinase 1)
[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:170629
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCRESAHA.117.310945


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[PMID]:28636643
[Au] Autor:Himori K; Tatebayashi D; Kanzaki K; Wada M; Westerblad H; Lanner JT; Yamada T
[Ad] Endereço:Graduate School of Health Sciences, Sapporo Medical University, Sapporo, Japan.
[Ti] Título:Neuromuscular electrical stimulation prevents skeletal muscle dysfunction in adjuvant-induced arthritis rat.
[So] Source:PLoS One;12(6):e0179925, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Skeletal muscle weakness is a prominent feature in patients with rheumatoid arthritis (RA). In this study, we investigated whether neuromuscular electrical stimulation (NMES) training protects against skeletal muscle dysfunction in rats with adjuvant-induced arthritis (AIA). AIA was produced by intraarticular injection of complete Freund's adjuvant into the knees of Wistar rats. For NMES training, dorsiflexor muscles were stimulated via a surface electrode (0.5 ms pulse, 50 Hz, 2 s on/4 s off). NMES training was performed every other day for three weeks and consisted of three sets produced at three min intervals. In each set, the electrical current was set to achieve 60% of the initial maximum isometric torque and the current was progressively increased to maintain this torque; stimulation was stopped when the 60% torque could no longer be maintained. After the intervention period, extensor digitorum longus (EDL) muscles were excised and used for physiological and biochemical analyses. There was a reduction in specific force production (i.e. force per cross-sectional area) in AIA EDL muscles, which was accompanied by aggregation of the myofibrillar proteins actin and desmin. Moreover, the protein expressions of the pro-oxidative enzymes NADPH oxidase, neuronal nitric oxide synthase, p62, and the ratio of the autophagosome marker LC3bII/LC3bI were increased in AIA EDL muscles. NMES training prevented all these AIA-induced alterations. The present data suggest that NMES training prevents AIA-induced skeletal muscle weakness presumably by counteracting the formation of actin and desmin aggregates. Thus, NMES training can be an effective treatment for muscle dysfunction in patients with RA.
[Mh] Termos MeSH primário: Artrite Experimental/terapia
Músculo Esquelético/metabolismo
[Mh] Termos MeSH secundário: Actinas/metabolismo
Animais
Artrite Experimental/metabolismo
Artrite Experimental/fisiopatologia
Desmina/metabolismo
Terapia por Estimulação Elétrica
Masculino
Proteínas Associadas aos Microtúbulos/metabolismo
Contração Muscular/fisiologia
Músculo Esquelético/efeitos dos fármacos
NADPH Oxidases/metabolismo
Óxido Nítrico Sintase Tipo I/metabolismo
Ácido Peroxinitroso/farmacologia
Ratos
Ratos Wistar
Proteína Sequestossoma-1/metabolismo
Superóxido Dismutase/metabolismo
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actins); 0 (Desmin); 0 (LC3 protein, rat); 0 (Microtubule-Associated Proteins); 0 (Sequestosome-1 Protein); 14691-52-2 (Peroxynitrous Acid); EC 1.14.13.39 (Nitric Oxide Synthase Type I); EC 1.15.1.1 (Superoxide Dismutase); EC 1.15.1.1 (superoxide dismutase 2); EC 1.6.3.- (NADPH Oxidases)
[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:170622
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179925


  9 / 3491 MEDLINE  
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[PMID]:28625393
[Au] Autor:Cuppens T; Depreeuw J; Annibali D; Thomas D; Hermans E; Gommé E; Trinh XB; Debruyne D; Moerman P; Lambrechts D; Amant F
[Ad] Endereço:KU Leuven - University of Leuven, Department of Oncology, Gynaecologic Oncology, B-3000 Leuven, Belgium.
[Ti] Título:Establishment and characterization of uterine sarcoma and carcinosarcoma patient-derived xenograft models.
[So] Source:Gynecol Oncol;146(3):538-545, 2017 Sep.
[Is] ISSN:1095-6859
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Uterine sarcomas (US) and carcinosarcomas (CS) are rare, aggressive cancers. The lack of reliable preclinical models hampers the search for new treatment strategies and predictive biomarkers. To this end, we established and characterized US and CS patient-derived xenograft (PDX) models. METHODS: Tumor fragments of US and CS were subcutaneously implanted into immunocompromised mice. Engrafted xenograft and original tumors were compared by means of histology, immunohistochemistry, whole-genome low-coverage sequencing for copy number variations, and RNA sequencing. RESULTS: Of 13 implanted leiomyosarcomas (LMS), 10 engrafted (engraftment rate of 77%). Also 2 out of 7 CS (29%) and one high-grade US (not otherwise specified) models were successfully established. LMS xenografts showed high histological similarity to their corresponding human tumors. Expression of desmin and/or H-caldesmon was detected in 8/10 LMS PDX models. We noticed that in CS models, characterized by the concomitant presence of a mesenchymal and an epithelial component, the relative distribution of the components is varying over the generations, as confirmed by changes in vimentin and cytokeratin expression. The similarity in copy number profiles between original and xenograft tumors ranged from 57.7% to 98.2% for LMS models and from 47.4 to 65.8% for CS models. Expression pattern stability was assessed by clustering RNA expression levels of original and xenograft tumors. Six xenografts clustered together with their original tumor, while 3 (all LMS) clustered apart. CONCLUSIONS: We present here a panel of clinically annotated uterine sarcoma and carcinosarcoma PDX models, which will be a useful tool for preclinical testing of new therapies.
[Mh] Termos MeSH primário: Carcinossarcoma/patologia
DNA de Neoplasias/análise
Modelos Animais de Doenças
Xenoenxertos/patologia
Leiomiossarcoma/patologia
RNA Neoplásico/análise
Neoplasias Uterinas/patologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Animais
Proteínas de Ligação a Calmodulina/análise
Carcinossarcoma/química
Carcinossarcoma/genética
Variações do Número de Cópias de DNA
Desmina/análise
Feminino
Expressão Gênica
Sobrevivência de Enxerto
Xenoenxertos/química
Seres Humanos
Leiomiossarcoma/química
Leiomiossarcoma/genética
Camundongos
Meia-Idade
Transplante de Neoplasias
Análise de Sequência de RNA
Transplante Heterólogo
Neoplasias Uterinas/química
Neoplasias Uterinas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calmodulin-Binding Proteins); 0 (DNA, Neoplasm); 0 (Desmin); 0 (RNA, Neoplasm)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE


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[PMID]:28492717
[Au] Autor:Sun LJ; Chen X; Dai YN; Xu CF; Ji F; Chen LH; Chen HT; Chen CX
[Ad] Endereço:Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University, Zhejiang, China.
[Ti] Título:Endoscopic Ultrasonography in the Diagnosis and Treatment Strategy Choice of Esophageal Leiomyoma.
[So] Source:Clinics (Sao Paulo);72(4):197-201, 2017 Apr.
[Is] ISSN:1980-5322
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES:: Esophageal leiomyoma is the most common benign tumor of the esophagus, and it originates from mesenchymal tissue. This study analyzed the clinicopathological characteristics of esophageal leiomyoma and aimed to evaluate the role of endoscopic ultrasonography in the diagnosis and treatment selection for these lesions. METHODS:: Two hundred and twenty-five patients who had suspected esophageal leiomyomas in endoscopic ultrasonography were enrolled at the Endoscopy Center of The First Affiliated Hospital, Zhejiang University from January 1st, 2009 to May 31th, 2015. The main outcomes included the demographic and morphological characteristics, symptoms, comparisons of diagnosis and treatment methods, adverse events, and prognosis. RESULTS:: One hundred and sixty-seven patients were diagnosed as having an esophageal leiomyoma by pathological examination. The mean patient age was 50.57±9.983 years. In total, 62.9% of the lesions originated from the muscularis mucosa, and the others originated from the muscularis propria. The median distance to the incisors was 30±12 cm. The median diameter was 0.72±0.99 cm. As determined by endoscopic ultrasonography, most existing leiomyomas were homogeneous, endophytic, and spherical. The leiomyomas from the muscularis mucosa were smaller than those from the muscularis propria and much closer to the incisors (p<0.05). SMA (smooth muscle antibody) (97.2%) and desmin (94.5%) were positive in the majority of patients. In terms of treatments, patients preferred endoscopic therapies, which led to less adverse events (e.g., intraoperative bleeding, local infection, pleural effusion) than surgical operations (p<0.05). The superficial leiomyomas presented less adverse events and better recovery (p<0.05) than deep leiomyomas. CONCLUSION:: Endoscopic ultrasonography has demonstrated high accuracy in the diagnosis of esophageal leiomyomas and provides great support in selecting treatments; however, EUS cannot completely avoid misdiagnosis, so combining it with other examinations may be a good strategy to solve this problem.
[Mh] Termos MeSH primário: Endossonografia/métodos
Neoplasias Esofágicas/diagnóstico por imagem
Leiomioma/diagnóstico por imagem
Mesenquimoma/diagnóstico por imagem
[Mh] Termos MeSH secundário: Adulto
Idoso
Acurácia dos Dados
Desmina/metabolismo
Ressecção Endoscópica de Mucosa/métodos
Endossonografia/normas
Neoplasias Esofágicas/patologia
Neoplasias Esofágicas/terapia
Feminino
Seres Humanos
Leiomioma/patologia
Leiomioma/terapia
Masculino
Mesenquimoma/patologia
Mesenquimoma/terapia
Meia-Idade
Músculo Liso/metabolismo
Estudos Retrospectivos
Tomografia/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Desmin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170830
[Lr] Data última revisão:
170830
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170512
[St] Status:MEDLINE



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