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Id: lil-796874
Autor: Dias, Queila Cristina; Nunes, Iseu da Silva; Garcia, Patrick Vianna; Fávaro, Wagner José.
Título: Potential therapeutic strategies for non - muscle invasive bladder cancer based on association of intravesical immunotherapy with P-MAPA and systemic administration of cisplatin and doxorubicin
Fonte: Int. braz. j. urol;42(5):942-954, Sept.-Oct. 2016. tab, graf.
Idioma: en.
Projeto: CNPq-Brazil; . FAPESP-Brazil.
Resumo: ABSTRACT The present study describes the histopathological and molecular effects of P-MAPA (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride) intravesical immunotherapy combined with systemic doxorubicin or cisplatin for treatment of non-muscle invasive bladder cancer (NMIBC) in an appropriate animal model. Our results showed an undifferentiated tumor, characterizing a tumor invading mucosa or submucosa of the bladder wall (pT1) and papillary carcinoma in situ (pTa) in the Cancer group. The histopathological changes were similar between the combined treatment with intravesical P-MAPA plus systemic Cisplatin and P-MAPA immunotherapy alone, showing decrease of urothelial neoplastic lesions progression and histopathological recovery in 80% of the animals. The animals treated systemically with cisplatin or doxorubicin singly, showed 100% of malignant lesions in the urinary bladder. Furthemore, the combined treatment with P-MAPA and Doxorubicin showed no decrease of urothelial neoplastic lesions progression and histopathological recovery. Furthermore, Akt, PI3K, NF-kB and VEGF protein levels were significantly lower in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments than other groups. In contrast, PTEN protein levels were significantly higher in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments. Thus, it could be concluded that combination of intravesical P-MAPA immunotherapy and systemic cisplatin in the NMIBC animal model was effective, well tolerated and showed no apparent signs of antagonism between the drugs. In addition, intravesical P-MAPA immunotherapy may be considered as a valuable option for treatment of BCG unresponsive patients that unmet the criteria for early cystectomy.
Descritores: Neoplasias da Bexiga Urinária/terapia
Carcinoma/terapia
Doxorrubicina/uso terapêutico
Cisplatino/uso terapêutico
Imunoterapia/métodos
Proteínas de Membrana/uso terapêutico
Antineoplásicos/uso terapêutico
-Ratos Endogâmicos F344
Neoplasias da Bexiga Urinária/patologia
Administração Intravesical
Vacina BCG
Carcinoma/patologia
Western Blotting
Reprodutibilidade dos Testes
NF-kappa B/análise
Resultado do Tratamento
Terapia Combinada
Progressão da Doença
Fosfatidilinositol 3-Quinases/análise
Modelos Animais
Fator A de Crescimento do Endotélio Vascular/análise
PTEN Fosfo-Hidrolase/análise
Proteínas Proto-Oncogênicas c-akt/análise
Limites: Animais
Feminino
Tipo de Publ: Estudo de Avaliação
Responsável: BR1.1 - BIREME


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Id: biblio-892869
Autor: Karagüzel, Ersagun; Menteşe, Ahmet; O. Kazaz, Ilke; Demir, Selim; Örem, Asim; Okatan, Ali Ertan; Altay, Diler Us; Yaman, Serap Özer.
Título: SCUBE1: a promising biomarker in renal cell cancer
Fonte: Int. braz. j. urol;43(4):638-643, July-Aug. 2017. tab.
Idioma: en.
Projeto: Karadeniz Technical University.
Resumo: ABSTRACT Purpose To investigate the efficacy of signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) as a novel biomarker of renal tumors. Materials and Methods 48 individuals were included in the study. The patient group (Group-1) consisted of 23 subjects diagnosed with renal tumor, and the control group (Group-2) of 25 healthy individuals. Patients diagnosed with renal tumor received surgical treatment consisting of radical or partial nephrectomy. Blood specimens were collected following overnight fasting. Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1), soluble urokinase plasminogen activator receptor (suPAR) and carbonic anhydrase IX (CA IX) levels were measured from plasma samples. Patients in groups 1 and 2 were compared in terms of these biochemical parameters. Results The 23-member renal tumor group was made up of 17 (73.91%) male and 6 (26.08%) female patients with a mean age of 58.5±15.7 years (range 25 to 80). The 24-member healthy control group was made up of 16 (64%) male and 9 (36%) female subjects with a mean age of 52.4±9.12 years (range 40 to 67). Analysis revealed significant elevation in SCUBE-1 levels in the renal tumor group (p=0.005). No significant differences were detected between the groups with regard to CA IX or suPAR measurements (p=0.062 vs. p=0.176). Conclusions SCUBE-1 appears to represent a promising biomarker in the diagnosis and follow-up of patients with renal tumor.
Descritores: Carcinoma de Células Renais/sangue
Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue
Anidrase Carbônica IX/sangue
Neoplasias Renais/sangue
Proteínas de Membrana/sangue
-Proteínas de Ligação ao Cálcio
Carcinoma de Células Renais/diagnóstico
Biomarcadores Tumorais/sangue
Estudos de Casos e Controles
Neoplasias Renais/diagnóstico
Pessoa de Meia-Idade
Limites: Humanos
Masculino
Feminino
Adulto
Idoso
Idoso de 80 Anos ou mais
Responsável: BR1.1 - BIREME


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Id: lil-467877
Autor: Murador, Priscila; Deffune, Elenice.
Título: Aspectos estruturais da membrana eritrocitária / Structural aspects of the erythrocyte membrane
Fonte: Rev. bras. hematol. hemoter;29(2):168-178, abr.-jun. 2007. ilus, tab.
Idioma: pt.
Resumo: Este artigo descreve as estruturas e funções da membrana eritrocitária e sua importância na medicina transfusional. A membrana eritrocitária é uma das membranas mais conhecidas em termos de estrutura, função e genética. Como qualquer membrana plasmática, tem como função mediar transportes e, ainda, fornece ao eritrócito resistência e maleabilidade. De acordo com a International Society of Blood Transfusion (ISBT), são mais de 500 antígenos expressos na membrana das hemácias e, destes, cerca de 270 estão envolvidos nos casos de reação transfusional e doença hemolítica do feto e do recém-nascido. Na classificação feita pela ISBT, destaca-se a série de alta freqüência representada por antígenos presentes em mais de 99 por cento dos indivíduos de uma população. Estes antígenos são conhecidos também como antígenos públicos e a maioria, quando ausente, determina problemas graves do ponto de vista transfusional. Como exemplo dessa problemática, uma gestante com ausência do antígeno P já sofreu seis abortos de repetição por insuficiência placentária devido ao anticorpo formado pela ausência do antígeno. Proteínas importantes são descritas nesta revisão como: banda 3, glicoforinas, espectrina e outras. A banda 3 é a mais abundante proteína integral da membrana do eritrócito e sua principal função é mediar a troca de cloro e ânions de bicarbonato através da membrana plasmática. A segunda proteína integral mais abundante é a sialoglicoproteína glicoforina A (GPA). Com um alto conteúdo de ácido siálico, a GPA contribui com a rede de carga negativa na superfície da membrana do eritrócito, minimizando, assim, a interação célula-célula e prevenindo sua agregação. Glicoforina C (GPC) é o receptor para PfEBP-2 (baebl, EBA-140), o mais novo local de ligação identificado para o Plasmodium falciparum.O complexo terciário - espectrina, actina e 4.1R - define a rede de citoesqueleto da membrana do eritrócito e é ainda responsável pela estabilidade sob mecanismos...

This article describes the structures and functions of the erythrocyte membrane and its importance in transfusional medicine. The erythrocyte membrane is one of the best known membranes in terms of structure, function and genetic disorders. As any other plasma membrane, it mediates transport functions. It also provides the erythrocytes with their resilience and deformability. According to the International Society of Blood Transfusion (ISBT), more than 500 antigens are expressed in the erythrocyte membrane, and around 270 are involved in transfusion reaction cases and hemolytic diseases of the fetus and newborn. In the ISBT classification, the high frequency series is represented by antigens in more than 99 percent of population (high prevalence antigen). In transfusion, the absence of these antigens determines severe problems as for example, one woman without the P antigen suffered 6 repetitive miscarriages due to placental insufficiency, which was caused by an antibody formed against the absent P antigen. Some important erythrocyte membrane proteins are described here including Band 3, Glycophorins and spectrin. The most abundant integral membrane protein is Band 3 and its main function is to mediate exchange of chloride and bicarbonate anions across the plasma membrane. The second most abundant integral membrane protein in the human erythrocyte is sialoglycoprotein glycophorin A (GPA). With its high sialic acid content, GPA is the main contributor to the net negative cell-surface charge and is thus critical for minimizing cell-cell interactions and preventing red cell aggregation. Glycophorin C (GPC) is the receptor for PfEBP-2 (baebl, EBA-140), the newly identified erythrocyte binding ligand of Plasmodium falciparum. The ternary complex of spectrin, actin and 4.1R defines the nodes of the erythrocyte membrane skeletal network, and is inseparable from membrane stability when under mechanical stress. This erythrocyte membrane review...
Descritores: Membrana Eritrocítica
-Transfusão de Sangue
Glicoforinas
Proteínas
Membrana Celular
Reação Transfusional
Proteínas de Membrana
Antígenos
Tipo de Publ: Revisão
Responsável: BR408.1 - Biblioteca da Faculdade de Medicina - BFM


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Id: biblio-950748
Autor: Shen, Cong-Cong; Kang, Yu-Huan; Yu, Lin; Cui, Dan-Dan; He, Yi; Yang, Jin-Liang; Gou, Lan-Tu.
Título: Human testis-expressed sequence 101 is limitedly distributed in germinal epithelium of testis and disappears in seminoma
Fonte: Biol. Res;47:1-6, 2014. ilus.
Idioma: en.
Projeto: National Natural Science Foundation of China; . National Science and Technology Major Projects of New Drugs.
Resumo: BACKGROUND: Testis-expressed sequence 101 (TEX101) was found to be highly expressed in testis and involved in acrosome reaction in previous studies. Recently, the metastasis suppressor function of TEX101 in cancer was disclosed, but the comprehensive investigation of its expression has rarely been reported. In this study, the expression features of TEX101 in normal human organs and seminoma were systematically analyzed. RESULTS: Immunohistochemistry demonstrated intense staining of TEX101 in human testis tissues; however, its expression in 27 other types of normal human organs, including the ovary, was negligible. Higher expression of TEX101 was observed in the spermatocytes and spermatids of the testis, but relatively lower staining was detected in spermatogonia. Western blotting showed a single TEX101 band of 38 kDa in human testis, but it did not correspond to the predicted molecular weight of its mature form at 21 KDa. Furthermore, we examined seminoma tissues by immunohistochemistry and found that none of the 36 samples expressed TEX101. CONCLUSIONS: Our data confirmed TEX101 to be a testis protein that could be related to the maturation process of male germ cells. The lack of TEX101 in seminoma indicated its potential role in tumor progression. This characteristic expression of TEX101 could provide a valuable reference for understanding its biological functions.
Descritores: Epitélio Seminífero/metabolismo
Neoplasias Testiculares/metabolismo
Seminoma/metabolismo
Proteínas de Membrana/metabolismo
-Especificidade de Órgãos/fisiologia
Ovário/metabolismo
Epitélio Seminífero/patologia
Maturação do Esperma/fisiologia
Espermatozoides/crescimento & desenvolvimento
Neoplasias Testiculares/patologia
Testículo/metabolismo
Testículo/patologia
Imuno-Histoquímica
Diferenciação Celular
Western Blotting
Seminoma/patologia
Trato Gastrointestinal/metabolismo
Epitélio/metabolismo
Tecido Linfoide/metabolismo
Tecido Nervoso/metabolismo
Limites: Humanos
Masculino
Feminino
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: CL1.1 - Biblioteca Central


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Id: biblio-1131887
Autor: Cao, Danxia; Zhu, Han; Zhao, Qian; Huang, Jianming; Zhou, Cixiang; He, Jianrong; Liang, Yongjun.
Título: MiR-128 suppresses metastatic capacity by targeting metadherin in breast cancer cells
Fonte: Biol. Res;53:43, 2020. tab, graf.
Idioma: en.
Projeto: Pudong Bureau of Health and Family Planning; . National Science Foundation of China.
Resumo: BACKGROUND: Breast cancer, the most common cancer in women worldwide, causes the vast majority of cancer-related deaths. Undoubtedly, tumor metastasis and recurrence are responsible for more than 90 percent of these deaths. MicroRNAs are endogenous noncoding RNAs that have been integrated into almost all the physiological and pathological processes, including metastasis. In the present study, the role of miR-128 in breast cancer was investigated. RESULTS: Compared to the corresponding adjacent normal tissue, the expression of miR-128 was significantly suppressed in human breast cancer specimens. More importantly, its expression level was reversely correlated to histological grade of the cancer. Ectopic expression of miR-128 in the aggressive breast cancer cell line MDA-MB-231 could inhibit cell motility and invasive capacity remarkably. Afterwards, Metadherin (MTDH), also known as AEG-1 (Astrocyte Elevated Gene 1) and Lyric that implicated in various aspects of cancer progression and metastasis, was further identified as a direct target gene of miR-128 and its expression level was up-regulated in clinical samples as expected. Moreover, knockdown of MTDH in MDA-MB-231 cells obviously impaired the migration and invasion capabilities, whereas re-expression of MTDH abrogated the suppressive effect caused by miR-128. CONCLUSIONS: Overall, these findings demonstrate that miR-128 could serve as a novel biomarker for breast cancer metastasis and a potent target for treatment in the future.
Descritores: Neoplasias da Mama/genética
MicroRNAs/fisiologia
MicroRNAs/genética
Invasividade Neoplásica/genética
-Moléculas de Adesão Celular/genética
Moléculas de Adesão Celular/metabolismo
Regulação Neoplásica da Expressão Gênica
Proteínas de Ligação a RNA
Linhagem Celular Tumoral
Proteínas de Membrana
Recidiva Local de Neoplasia
Limites: Humanos
Feminino
Responsável: CL1.1 - Biblioteca Central


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Id: biblio-950858
Autor: Simm, Stefan; Einloft, Jens; Mirus, Oliver; Schleiff, Enrico.
Título: 50 years of amino acid hydrophobicity scales: revisiting the capacity for peptide classification
Fonte: Biol. Res;49:1-19, 2016. ilus, graf, tab.
Idioma: en.
Projeto: Deutsche Forschungsgemein.
Resumo: BACKGROUND: Physicochemical properties are frequently analyzed to characterize protein-sequences of known and unknown function. Especially the hydrophobicity of amino acids is often used for structural prediction or for the detection of membrane associated or embedded ß-sheets and α-helices. For this purpose many scales classifying amino acids according to their physicochemical properties have been defined over the past decades. In parallel, several hydrophobicity parameters have been defined for calculation of peptide properties. We analyzed the performance of separating sequence pools using 98 hydrophobicity scales and five different hydrophobicity parameters, namely the overall hydrophobicity, the hydrophobic moment for detection of the α-helical and ß-sheet membrane segments, the alternating hydrophobicity and the exact ß-strand score. RESULTS: Most of the scales are capable of discriminating between transmembrane α-helices and transmembrane ß-sheets, but assignment of peptides to pools of soluble peptides of different secondary structures is not achieved at the same quality. The separation capacity as measure of the discrimination between different structural elements is best by using the five different hydrophobicity parameters, but addition of the alternating hydrophobicity does not provide a large benefit. An in silico evolutionary approach shows that scales have limitation in separation capacity with a maximal threshold of 0.6 in general. We observed that scales derived from the evolutionary approach performed best in separating the different peptide pools when values for arginine and tyrosine were largely distinct from the value of glutamate. Finally, the separation of secondary structure pools via hydrophobicity can be supported by specific detectable patterns of four amino acids. CONCLUSION: It could be assumed that the quality of separation capacity of a certain scale depends on the spacing of the hydrophobicity value of certain amino acids. Irrespective of the wealth of hydrophobicity scales a scale separating all different kinds of secondary structures or between soluble and transmembrane peptides does not exist reflecting that properties other than hydrophobicity affect secondary structure formation as well. Nevertheless, application of hydrophobicity scales allows distinguishing between peptides with transmembrane α-helices and ß-sheets. Furthermore, the overall separation capacity score of 0.6 using different hydrophobicity parameters could be assisted by pattern search on the protein sequence level for specific peptides with a length of four amino acids.
Descritores: Interações Hidrofóbicas e Hidrofílicas
Aminoácidos/química
Proteínas de Membrana/química
-Valores de Referência
Fatores de Tempo
Pesos e Medidas
Algoritmos
Valor Preditivo dos Testes
Reprodutibilidade dos Testes
Sequência de Aminoácidos
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Aminoácidos/classificação
Responsável: CL1.1 - Biblioteca Central


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Id: biblio-838089
Autor: Handa, Priya; Maliken, Bryan D; Nelson, James E; Hennessey, Kelly A; Vemulakonda, L. Akhila; Morgan-Stevenson, Vicki; Dhillon, Barjinder K; Gupta, Rohit; Yeh, Matthew M; Kowdley, Kris V.
Título: Differences in Hepatic Expression of Iron, Inflammation and Stress-Related Genes in Patients with Nonalcoholic Steatohepatitis
Fonte: Ann. hepatol;16(1):77-85, Jan.-Feb. 2017. graf.
Idioma: en.
Resumo: Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. We have previously shown that hepatic reticuloendothelial system (RES) iron deposition is associated with an advanced degree of nonalcoholic steatohepatitis (NASH) in humans. In this study, we aimed to determine differentially expressed genes related to iron overload, inflammation and oxidative stress pathways, with the goal of identifying factors associated with NASH progression. Seventy five patients with NAFLD were evaluated for their biochemical parameters and their liver tissue analyzed for NASH histological characteristics. Gene expression analysis of pathways related to iron homeostasis, inflammation and oxidative stress was performed using real-time PCR. Gene expression was compared between subjects based on disease status and presence of hepatic iron staining. We observed increased gene expression of hepcidin (HAMP) (2.3 fold, p = 0.027), transmembrane serine proteinase 6 (TMPRSS6) (8.4 fold, p = 0.003), signal transducer and activator of transcription 3 (STAT3) (5.5 fold, p = 0.004), proinflammatory cytokines; IL-1β (2.7 fold, p = 0.046) and TNF-α (3.8 fold, p = 0.001) in patients with NASH. TMPRSS6, a negative regulator of HAMP, is overexpressed in patients with NASH and HIF1α (hypoxia inducible factor-1) is downregulated. NAFLD patients with hepatic iron deposition exhibited higher hepcidin expression (3.1 fold, p = 0.04) but lower expression of cytokines. In conclusion, we observed elevated hepatic HAMP expression in patients with NASH and in NAFLD patients who had hepatic iron deposition, while proinflammatory cytokines displayed elevated expression only in patients with NASH, suggesting a regulatory role for hepcidin in NAFL to NASH transition and in mitigating inflammatory responses.
Descritores: Estresse Oxidativo/genética
Sobrecarga de Ferro/genética
Hepatopatia Gordurosa não Alcoólica/genética
Inflamação/genética
Ferro/análise
Fígado/química
-Serina Endopeptidases/genética
Regulação da Expressão Gênica
Fator de Necrose Tumoral alfa/genética
Fator de Necrose Tumoral alfa/sangue
Mediadores da Inflamação/sangue
Sobrecarga de Ferro/diagnóstico
Sobrecarga de Ferro/sangue
Fator de Transcrição STAT3/genética
Interleucina-1beta/genética
Interleucina-1beta/sangue
Reação em Cadeia da Polimerase em Tempo Real
Hepcidinas/genética
Hepatopatia Gordurosa não Alcoólica/diagnóstico
Hepatopatia Gordurosa não Alcoólica/sangue
Inflamação/diagnóstico
Inflamação/sangue
Fígado/patologia
Proteínas de Membrana/genética
Limites: Humanos
Masculino
Feminino
Pessoa de Meia-Idade
Responsável: BR1.1 - BIREME


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Id: biblio-950870
Autor: Pérez-Ibave, Diana Cristina; González-Alvarez, Rafael; Martinez-Fierro, Margarita de La Luz; Ruiz-Ayma, Gabriel; Luna-Munoz, Maricela; Martínez-De-Villarreal, Laura Elia; Garza-Rodríguez, María De Lourdes; Reséndez-Pérez, Diana; Mohamed-Noriega, Jibran; Garza-Guajardo, Raquel; Bautista-De-Lucío, Victor Manuel; Mohamed-Noriega, Karim; Barboza-Quintana, Oralia; Arámburo-De-La-Hoz, Carlos; Barrera-Saldana, Hugo Alberto; Rodríguez-Sánchez, Irám Pablo.
Título: Olfactomedin-like 2 A and B (OLFML2A and OLFML2B) expression profile in primates (human and baboon)
Fonte: Biol. Res;49:1-12, 2016. ilus, graf, tab.
Idioma: en.
Projeto: Mexican Council of Science and Technology.
Resumo: BACKGROUND: The olfactomedin-like domain (OLFML) is present in at least four families of proteins, including OLFML2A and OLFML2B, which are expressed in adult rat retina cells. However, no expression of their orthologous has ever been reported in human and baboon. OBJECTIVE: The aim of this study was to investigate the expression of OLFML2A and OLFML2B in ocular tissues of baboons (Papio hamadryas) and humans, as a key to elucidate OLFML function in eye physiology. METHODS: OLFML2A and OLFML2B cDNA detection in ocular tissues of these species was performed by RT-PCR. The amplicons were cloned and sequenced, phylogenetically analyzed and their proteins products were confirmed by immunofluorescence assays. RESULTS: OLFML2A and OLFML2B transcripts were found in human cornea, lens and retina and in baboon cornea, lens, iris and retina. The baboon OLFML2A and OLFML2B ORF sequences have 96% similarity with their human's orthologous. OLFML2A and OLFML2B evolution fits the hypothesis of purifying selection. Phylogenetic analysis shows clear orthology in OLFML2A genes, while OLFML2B orthology is not clear. CONCLUSIONS: Expression of OLFML2A and OLFML2B in human and baboon ocular tissues, including their high similarity, make the baboon a powerful model to deduce the physiological and/or metabolic function of these proteins in the eye.
Descritores: Glicoproteínas/metabolismo
Proteínas da Matriz Extracelular/metabolismo
Olho/metabolismo
Proteínas de Membrana/metabolismo
-Papio
Valores de Referência
Glicoproteínas/análise
Glicoproteínas/genética
Proteínas da Matriz Extracelular/análise
Proteínas da Matriz Extracelular/genética
Imunofluorescência/métodos
Evolução Molecular
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Análise de Sequência de Proteína
Transcrição Reversa
Olho/química
Código de Barras de DNA Taxonômico
Proteínas de Membrana/análise
Proteínas de Membrana/genética
Fenômenos Fisiológicos Oculares
Limites: Humanos
Animais
Responsável: CL1.1 - Biblioteca Central


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Id: biblio-950906
Autor: Huang, Chengchi; Lu, Hong; Xu, Junyu; Yu, Hongmin; Wang, Xiaodan; Zhang, Xiaomei.
Título: Protective roles of autophagy in retinal pigment epithelium under high glucose condition via regulating PINK1/Parkin pathway and BNIP3L
Fonte: Biol. Res;51:22, 2018. graf.
Idioma: en.
Projeto: Health and Family Planning Commission in Heilongjiang Province.
Resumo: BACKGROUND: Our study aimed to investigate the roles of autophagy against high glucose induced response in retinal pigment epithelium (ARPE-19 cells). METHODS: The morphological changes and reactive oxygen species (ROS) generation in ARPE-19 cells under high glucose treatment were respectively detected using the transmission electron microscopy and flow cytometry. The expression levels of Parkin, PINK1, BNIP3L, LC3-I and LC3-II in ARPE-19 cells received high glucose treatment were measured by western blot after pretreatment of carbonyl cyanide m-chlorophenylhydrazone (CCCP), 3-methyladenine (3-MA), N-acetyl cysteine (NAC) or cyclosporin A (CsA) followed by high glucose treatment. RESULTS: ARPE-19 cells subjected to high glucose stress showed an obvious reduction in the LC3-I expression and significant increase in the number of autophagosomes, in the intracellular ROS level, and in the expression levels of Parkin, PINK1, BNIP3L and LC3-II (p < 0.05). Pretreatment with CCCP significantly reduced the LC3-I expression and increased the expression levels of Parkin, PINK1, BNIP3L and LC3-II (p < 0.05). ARPE-19 cells pretreated with CsA under high glucose stress showed markedly down-regulated expressions of Parkin, PINK1 and BNIP3L compared with the cells treated with high glucose (p < 0.05). Pretreatment of ARPE-19 cells with NAC or 3-MA under high glucose stress resulted in a marked reduction in the expression levels of PINK1, BNIP3L and LC3-II (p < 0.05). Meanwhile, the expression level of Parkin in the ARPE-19 cells pretreated with NAC under high glucose stress was comparable with that in the control cells. CONCLUSION: Autophagy might have protective roles against high glucose induced injury in ARPE19 cells via regulating PINK1/Parkin pathway and BNIP3L.
Descritores: Proteínas Quinases/efeitos dos fármacos
Autofagia/efeitos dos fármacos
Proteínas Proto-Oncogênicas/efeitos dos fármacos
Proteínas Supressoras de Tumor/efeitos dos fármacos
Ubiquitina-Proteína Ligases/efeitos dos fármacos
Epitélio Pigmentado da Retina/efeitos dos fármacos
Glucose/farmacologia
Proteínas de Membrana/efeitos dos fármacos
-Proteínas Quinases/metabolismo
Autofagia/fisiologia
Transdução de Sinais/fisiologia
Linhagem Celular
Proteínas Proto-Oncogênicas/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Proteínas Supressoras de Tumor/metabolismo
Ubiquitina-Proteína Ligases/metabolismo
Microscopia Eletrônica de Transmissão
Epitélio Pigmentado da Retina/citologia
Citometria de Fluxo
Proteínas de Membrana/metabolismo
Limites: Humanos
Responsável: CL1.1 - Biblioteca Central


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Texto completo
Id: biblio-1011404
Autor: Li, Ling; Liu, Ming; Zhang, Zhihu; Zhang, Wei; Liu, Naifu; Sheng, Xiugui; Wei, Ping.
Título: Derlin1 functions as an oncogene in cervical cancer via AKT/mTOR signaling pathway
Fonte: Biol. Res;52:8, 2019. tab, graf.
Idioma: en.
Resumo: BACKGROUND: Cervical cancer (CC) ranks third in the morbidity and mortality of female cancer around the world. Derlin1 has been found to be overexpressed in several human cancers. However, it is still unclear about its roles in CC. The research aims to explore the relationship between Derlin1 and CC. METHODS: We purchased a human CC tissues microarray, which contained CC tissues and corresponding para-cancerous tissues from 93 patients with primary cervical squamous cell carcinoma. Immunohistochemical staining was used to confirm the expression of Derlin1 in these tissues. And we detected the differential expression of Derlin1 in cervical cancer cell lines and normal cervical epithelial cells (H8). Further, the cervical cancer cell lines SiHa and C33A were used as an in vitro model, which was down-regulated the expression of Derlin1 using siRNA interference technology. The effects of Derlin1 down-regulating in CC cell lines on cell proliferation and migration were detected by CCK8 assay and transwell assay, respectively. The effect of Derlin1 down-regulating on apoptosis was analyzed by flow cytometry, and apoptosis-related proteins were detected using western blotting. In-depth mechanisms were studied using western blotting. In addition, the effects of Derlin1 up-regulating in normal cervical epithelial cells also were exposed. RESULTS: Derlin1 was significantly elevated in CC tissues (81.7%, 76/93), and the expression of Derlin 1 was positively correlated with the tumor size, pathological grade, and lymph node metastasis in CC patients. And Derlin 1 was high expressed in cervical cancer cell lines compared to H8 cells. Knockdown of Derlin 1 in cervical cancer cell lines inhibited cell proliferation and migration. Moreover, knockdown of Derlin 1 induced apoptosis and affected the expression of apoptosis-related proteins, including Bcl-2, Bax, Bim, caspase3 and caspase9. Further experiments showed that AKT/mTOR signal pathway might be involve in this processes that knockdown of Derlin 1 inhibited the expression of p-AKT and p-mTOR. Over-expression of Derlin 1 in H8 cells promoted cell proliferation and migration via up-regulated the expression of p-AKT and p-mTOR. CONCLUSION: Derlin 1 is an oncogene in CC via AKT/mTOR pathway. It might be a potential therapeutic target for CC.
Descritores: Carcinoma de Células Escamosas/metabolismo
Transdução de Sinais/fisiologia
Neoplasias do Colo do Útero/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Serina-Treonina Quinases TOR/metabolismo
Proteínas de Membrana/metabolismo
-Imuno-Histoquímica
Carcinoma de Células Escamosas/patologia
Neoplasias do Colo do Útero/patologia
Apoptose
Análise Serial de Proteínas
Linhagem Celular Tumoral
Proliferação de Células
Proteínas Proto-Oncogênicas c-akt/fisiologia
Limites: Humanos
Feminino
Tipo de Publ: Carta
Responsável: CL1.1 - Biblioteca Central



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