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1.
Revista Digital de Postgrado ; 10(1): 275, abr. 2021. tab
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1147596

RESUMO

El hígado graso del embarazo es una patología poco frecuente en la especialidad obstétrica, cuyo diagnóstico se realiza basado en los criterios de Swansea, muchas veces es un diagnóstico que se realiza por exclusión; usualmente se presenta entre las semanas 30 y 35 del embarazo, y la cura definitiva se realiza con la interrupción expedita del mismo; con una tasa de recuperación casi del 100% si se realiza la interrupción oportuna y una tasa de mortalidad materno fetal actual del 10%. Es importante estar atentos a la ganancia ponderal de la embarazada durante el control prenatal, la epigastralgia, y los signos clínicos asociados a hipoglicemia(AU)


Fatty liver of pregnancy is a rare pathology in obstetrics, whose diagnosis is made based on the Swansea criteria, many times it is a diagnosis that is made by exclusion; It usually occurs between weeks 30 and 35, and the definitive cure is carried out with the expeditious interruption of pregnancy; with a recovery rate of almost 100% if timely interruption is made and a current maternal-fetal mortality rate of 10%. It is important to be attentive to the weight gain of the pregnant woman during prenatal control, epigastric pain, and clinical signs associated with hypoglycemia


Assuntos
Humanos , Feminino , Gravidez , Síndrome HELLP , Aborto , Fígado Gorduroso/patologia , Hipoglicemia , Mortalidade Materna , Mortalidade Fetal , Técnicas de Diagnóstico Obstétrico e Ginecológico
2.
Rev. venez. oncol ; 33(1): 46-59, mar. 2021. tab
Artigo em Espanhol | LILACS, LIVECS | ID: biblio-1147479

RESUMO

El cáncer de mama Triple Negativo es un subtipo molecular que se caracteriza por ausencia de expresión de receptores de estrógeno, progesterona y proteína HER2. Representa el 10 % a 15 % de todos los subtipos de cáncer de mama con impacto en el pronóstico y en las líneas de tratamiento; siendo negativo para receptores hormonales y HER2, la terapéutica hormonal y anti-HER2 no cuentan para su manejo. Aún no se dispone de productos dirigidos a blancos específicos para esta categoría.(AU)


The Triple Negative breast cancer is a molecular subtype characterized by no expression of the estrogen, the progesterone and the HER2 protein receptors. They represents 10 % to 15 % of all the breast cancer subtypes with an impact on the prognosis and in the treatment lines; is negative for the hormone receptors and for the HER2, hormonal and the anti-HER2 therapeutics do not count for the management of them. The products targeting specific to this category are not yet available(AU)


Assuntos
Humanos , Feminino , Biomarcadores Tumorais , Antraciclinas/uso terapêutico , Taxoides/uso terapêutico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/epidemiologia , Mamografia , Tratamento Farmacológico , Oncologia
3.
Biol Res ; 54(1): 6, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33612118

RESUMO

BACKGROUND: Mitochondria play a significant role in plant cytoplasmic male sterility (CMS). In our previous study, mitochondrial complex I genes, nad4, nad5, and nad7 showed polymorphisms between the transgenic CMS line M2BS and its wild type M2B. The sterility mechanism of the M2BS at cytological, physiological, biochemical, and molecular level is not clear. RESULTS: Cytological observation showed that the anthers were light yellow, fissured, invalid in KI-I2, and full of irregularly typical abortion pollen grains in M2BS. Transmission electron microscopic (TEM) observation revealed no nucleus and degraded mitochondria with obscure cristae in anther cells of M2BS. The results of staining for H2O2 presented a large number of electron dense precipitates (edp) in intercellular space of anther cells of M2BS at anthesis. Moreover, the anther respiration rate and complex I activity of M2BS were significantly lower than those of wild type M2B during pollen development. Furthermore, RNA editing results showed only nad7 presented partially edited at 534th nucleotides. The expression of nad5 and nad7 revealed significant differences between M2B and M2BS. CONCLUSIONS: Our data demonstrated that mitochondrial structural degradation and complex I deficiency might be associated with transgenic CMS of rice.


Assuntos
Complexo I de Transporte de Elétrons/genética , Mitocôndrias/patologia , Oryza , Infertilidade das Plantas , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio , Mitocôndrias/ultraestrutura , Oryza/genética , Plantas Geneticamente Modificadas
4.
BMC Surg ; 21(1): 97, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33618677

RESUMO

BACKGROUND: In patients who are critically ill with COVID-19, multiple extrapulmonary manifestations of the disease have been observed, including gastrointestinal manifestations. CASE PRESENTATION: We present a case of a 65 year old man with severe COVID-19 pneumonia that developed hypercoagulation and peritonitis. Emergent laparotomy was performed and we found bowel necrosis in two sites. CONCLUSIONS: Although rare, the presentation of COVID-19 with bowel necrosis requires emergency treatments, and it has high mortality rate.


Assuntos
Enteropatias , Idoso , /terapia , Humanos , Enteropatias/patologia , Enteropatias/virologia , Masculino , Necrose , Índice de Gravidade de Doença
5.
BMJ Case Rep ; 14(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526525

RESUMO

We present a case of multifocal laryngotracheal amyloidosis (LTA) in a 43-year-old man with persistent and progressive dysphonia and dyspnoea, and a first inconclusive histology. Although laryngeal amyloidosis accounts for fewer than 1% of all benign laryngeal tumours, it is in fact the most common site of amyloid deposition in the head, neck and respiratory tract. The clinical scenario is non-specific and diagnosis depends on a high degree of suspicion and on histology. Imaging is useful in mapping lesions, which are often more extensive than they appear during laryngoscopy. Despite being a benign entity, the prognosis is variable with a high-rate and long-latency recurrences, requiring long-term follow-up.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Doenças da Laringe/diagnóstico por imagem , Doenças da Traqueia/diagnóstico por imagem , Adulto , Broncoscopia , Disfonia/fisiopatologia , Dispneia/fisiopatologia , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Amiloidose de Cadeia Leve de Imunoglobulina/fisiopatologia , Doenças da Laringe/patologia , Doenças da Laringe/fisiopatologia , Laringoscopia , Masculino , Tomografia Computadorizada por Raios X , Doenças da Traqueia/patologia , Doenças da Traqueia/fisiopatologia
6.
BMJ Case Rep ; 14(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526526

RESUMO

Pilomatrixoma is a benign subcutaneous tumour arising from the sebaceous glands. Mutation in the CTNNB1 gene is seen, suggesting beta-catenin misregulation may be the cause of pilomatrixoma. The preoperative diagnosis may be improved by the awareness of the fact that pilomatrixoma is a common and benign skin tumour of the head and neck region. It presents as a well-defined mass, which may be firm to hard in consistency, usually attached to the skin, but not to the underlying tissue. The colour of overlying skin appears a reddish-brown tinge, indicating that it could be a case of pilomatrixoma. Here, we report a case of pilomatrixoma of the cheek in a woman along with the CT findings and histopathological appearances. Dental surgeons should consider it as one of the differential diagnosis in superficial head and neck swelling with calcification.


Assuntos
Calcinose/diagnóstico por imagem , Doenças do Cabelo/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Pilomatrixoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Adulto , Calcinose/patologia , Feminino , Doenças do Cabelo/patologia , Doenças do Cabelo/cirurgia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Pilomatrixoma/patologia , Pilomatrixoma/cirurgia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Tomografia Computadorizada por Raios X
7.
BMJ Case Rep ; 14(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526529

RESUMO

Mixed epithelial-stromal tumours (MESTs) of the seminal vesicle (SV) are a rare neoplasm, with biological behaviour ranging from benign to malignant. Due to their rarity, there are no established guidelines for their treatment. We report a 37-year-old man with a large MEST of the SV which was successfully resected by laparoscopic transperitoneal approach. Amidst the controversy regarding the nomenclature and grading of MESTs in literature, we reclassified the previous reports of MESTs incorporating both the WHO and Reikie et al grading.


Assuntos
Neoplasias dos Genitais Masculinos/cirurgia , Neoplasias Complexas Mistas/cirurgia , Glândulas Seminais/cirurgia , Adulto , Cistadenoma/diagnóstico por imagem , Cistadenoma/patologia , Cistadenoma/cirurgia , Neoplasias dos Genitais Masculinos/complicações , Neoplasias dos Genitais Masculinos/diagnóstico por imagem , Neoplasias dos Genitais Masculinos/patologia , Humanos , Laparoscopia , Imagem por Ressonância Magnética , Masculino , Gradação de Tumores , Neoplasias Complexas Mistas/complicações , Neoplasias Complexas Mistas/diagnóstico por imagem , Neoplasias Complexas Mistas/patologia , Tumor Filoide/diagnóstico por imagem , Tumor Filoide/patologia , Tumor Filoide/cirurgia , Glândulas Seminais/diagnóstico por imagem , Glândulas Seminais/patologia , Retenção Urinária/etiologia
8.
BMJ Case Rep ; 14(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526532

RESUMO

Polyangiitis overlap syndrome (POS) is a diagnostic term coined by Leavitt and Fauci that characterises patients with overlapping features of more than one vasculitis. Prior case studies of antineutrophil cytoplasmic antibodies (ANCA)-associated POS have only been published in patients with eosinophilic granulomatosis with polyangiitis (EGPA) and granulomatosis with polyangiitis alongside proteinase-3/cytoplasmic (C)-ANCA positivity. We present a case of a 60-year-old woman with dyspnoea, hemoptysis, positive perinuclear-ANCA and renal biopsy demonstrating evidence of microscopic polyangiitis. In addition, our patient also had asthma, mononeuritis multiplex, eosinophilia and migratory pulmonary infiltrates, thus fulfilling the criteria for EGPA. This novel case report suggests that POS is not limited to C-ANCA positivity and has variable presentations.


Assuntos
Síndrome de Churg-Strauss/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Poliangiite Microscópica/diagnóstico , Mononeuropatias/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Azatioprina/uso terapêutico , Síndrome de Churg-Strauss/tratamento farmacológico , Síndrome de Churg-Strauss/imunologia , Síndrome de Churg-Strauss/fisiopatologia , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Poliangiite Microscópica/tratamento farmacológico , Poliangiite Microscópica/imunologia , Poliangiite Microscópica/fisiopatologia , Pessoa de Meia-Idade , Peroxidase/imunologia , Prednisona/uso terapêutico , Insuficiência Renal Crônica/patologia , Tomografia Computadorizada por Raios X
9.
Int J Mol Med ; 47(4): 1, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33537802

RESUMO

Paris saponin H (PSH) is a type of steroid saponin derived from Rhizoma Paridis (RP; the rhizome of Paris). In our previous studies, saponins from RP exerted antiglioma activity in vitro. However, the effects of PSH on glioma have not been elucidated. The aim of the present study was to evaluate the effects of PSH on U251 glioblastoma cells and elucidate the possible underlying mechanism. The cells were treated with PSH at various concentrations for 48 h, and the cell viability, invasion, apoptosis and cycle progression were assessed using specific assay kits. The activation of Akt, 44/42­mitogen­activated protein kinase (MAPK) and the expression levels of A1 adenosine receptor (ARA1) and ARA3 were assessed by western blotting. The results demonstrated that PSH inhibited cell viability, migration and invasion, and induced apoptosis. Treatment of U251 cells with PSH induced the upregulation of p21 and p27, and the downregulation cyclin D1 and S­phase kinase associated protein 2 protein expression levels, which induced cell cycle arrest at the G1 phase. The results also demonstrated that PSH inhibited the expression of ARA1, and the agonist of ARA1, 2­chloro­N6­cyclopentyladenosine, reversed the effects of PSH. Hypoxia induced increases in the ARA3, hypoxia­inducible factor­1α (HIF­1α) and vascular endothelial growth factor (VEGF) protein expression levels, which were associated with the activation of the Akt and P44/42 MAPK pathways. Compared with the hypoxia group, PSH inhibited the expression levels of ARA3, HIF­1α and VEGF, as well as the phosphorylation levels of Akt and 44/42 MAPK, and repressed HIF­1α transcriptional activity. Furthermore, the results demonstrated that PSH inhibited the expression of HIF­1α by inhibiting the phosphorylation of Akt and 44/42 MAPK mediated by ARA3. Taken together, these results suggested that PSH reduced U251 cell viability via the inhibition of ARA1 and ARA3 expression, and further inhibited Akt and 44/42 MAPK phosphorylation, induced apoptosis and cell cycle arrest.


Assuntos
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Glioma/metabolismo , Glioma/patologia , Receptor A1 de Adenosina/metabolismo , Receptor A3 de Adenosina/metabolismo , Saponinas/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fase G1/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Int J Mol Med ; 47(4): 1, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33537804

RESUMO

Quercetin (Quer) is a typical antioxidant flavonoid from plants that is involved in bone metabolism, as well as in the progression of inflammatory diseases. Elevated levels of tumor necrosis factor­α (TNF­α), a typical pro­inflammatory cytokine, can affect osteogenesis. In the present study, TNF­α was used to establish an in vitro model of periodontitis. The effects of Quer on, as well as its potential role in the osteogenic response of human periodontal ligament stem cells (hPDLSCs) under TNF­α­induced inflammatory conditions and the underlying mechanisms were then investigated. Within the appropriate concentration range, Quer did not exhibit any cytotoxicity. More importantly, Quer significantly attenuated the TNF­α induced the suppression of osteogenesis­related genes and proteins, alkaline phosphatase (ALP) activity and mineralized matrix in the hPDLSCs. These findings were associated with the fact that Quer inhibited the activation of the NF­κB signaling pathway, as well as the expression of NLRP3 inflammation­associated proteins in the inflammatory microenvironment. Moreover, the silencing of NLRP3 by small interfering RNA (siRNA) was found to protect the hPDLSCs against TNF­α­induced osteogenic damage, which was in accordance with the effects of Quer. On the whole, the present study demonstrates that Quer reduces the impaired osteogenesis of hPDLSCs under TNF­α­induced inflammatory conditions by inhibiting the NF­κB/NLRP3 inflammasome pathway. Thus, Quer may prove to be a potential remedy against periodontal bone defects.


Assuntos
Inflamassomos/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Osteogênese/efeitos dos fármacos , Ligamento Periodontal/patologia , Quercetina/farmacologia , Células-Tronco/patologia , Fator de Necrose Tumoral alfa/toxicidade , Adolescente , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Adulto Jovem
11.
Int J Mol Med ; 47(4): 1, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33537813

RESUMO

The activation of oxidative stress is a primary cause of chondrocyte apoptosis in osteoarthritis (OA). The 78­kDa glucose­regulated protein (GRP78)/mammalian target of rapamycin (mTOR) signaling pathway has been demonstrated to be linked with the endoplasmic reticulum (ER) and autophagy. Hydrogen sulfide (H2S) has been reported to exert antioxidant effects. The present study investigated oxidative stress levels via 2',7'­dichlorofluorescin diacetate and MitoSOX staining, apoptosis rates via flow cytometry and the expression levels of ER stress­related proteins in GYY4137 (donor of H2S)­treated chondrocytes (CHs). CHs were isolated from the bilateral hip joints of male rats to examine mitochondrial permeability transition pore opening­ and mTOR signaling pathway­related proteins. The results demonstrated that tert­Butyl hydroperoxide (TBHP) increased CH apoptosis, and treatment with GYY4137 ameliorated TBHP­mediated the generation of ROS and CH apoptosis. Moreover, TBHP­treated CHs displayed elevated ER stress sensor expression levels and apoptotic rates; however, the TBHP­induced protein expression levels were decreased following GYY4137 treatment. In the present study, treatment with either GYY4137 or transfection with GRP78 siRNA both suppressed the activation of p­P70S6k and p­mTOR. H2S played an important role in regulating ER stress in TBHP­stimulated CHs. GYY4137 promoted autophagy, which was accompanied by the inhibition of ER stress. On the whole, the present study demonstrates that TBHP­induced oxidative stress stimulates ER interactions and CH apoptosis, which are suppressed by exogenous H2S via modulating the GRP78/mTOR signaling pathway.


Assuntos
Condrócitos/metabolismo , Condrócitos/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas de Choque Térmico/metabolismo , Sulfeto de Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cloroquina/farmacologia , Condrócitos/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Masculino , Morfolinas/química , Morfolinas/farmacologia , Compostos Organotiofosforados/química , Compostos Organotiofosforados/farmacologia , Peróxidos/farmacologia , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
12.
Int J Mol Med ; 47(4): 1, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33537817

RESUMO

Inflammation is the most common cause of most acute and chronic debilitating diseases. Towards unveiling novel therapeutic options for patients with such complications, N­bromotaurine (TauNHBr) has emerged as a potential anti­inflammatory agent; however, its therapeutic efficacy is hindered due to its relatively poor stability. To address this challenge, the present study focused on examining the effects of a stable active bromine compound, named bromamine T (BAT). The present study examined the protective properties of BAT against lipopolysaccharide (LPS)­mediated inflammation in vitro, by using LPS­stimulated murine J774.A1 macrophages (Mφs), as well as in vivo, by using a murine LPS­mediated air­pouch model. Additionally, its efficacy was compared with that of taurine, a known potent anti­inflammatory molecule. In LPS­stimulated J774A.1 Mφs, BAT and taurine were very effective in reducing the secretion of pro­inflammatory mediators. The in vitro experiments indicated that LPS­mediated inflammation was attenuated due to the protective properties of BAT and of taurine, probably through the inhibition of phosphorylated p65 NF­κB subunit (Ser 536) nuclear translocation. The in vivo experiments also revealed that BAT and taurine inhibited LPS­mediated inflammation by reducing total cell/polymorphonuclear cell (PMN) infiltration in the air­pouch and by decreasing pouch wall thickness. The analysis of exudates obtained from pouches highlighted that the inhibitory effects of BAT and taurine on the secretion of pro­inflammatory cytokines were similar to those observed in vitro. Notably, the effect of BAT at the highest concentration tested was superior to that of taurine at the highest concentration. Taken together, the findings of the present study indicate that BAT prevents the LPS­induced inflammatory response both in vitro and in vivo.


Assuntos
Bromo/uso terapêutico , Inflamação/tratamento farmacológico , Sulfonamidas/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Bromo/farmacologia , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sulfonamidas/farmacologia , Taurina/farmacologia , Fator de Transcrição RelA/metabolismo , Transcrição Genética/efeitos dos fármacos
13.
Int J Mol Med ; 47(4): 1, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33537821

RESUMO

Endothelial dysfunction and diabetic vascular disease induced by chronic hyperglycemia involve complex interactions among high glucose, long non­coding RNAs (lncRNAs), microRNAs (miRNAs or miRs) and the Ser/Thr kinase AKT. However, the molecular mechanisms underlying the regulatory crosstalk between these have not yet been completely elucidated. Thus, the present study aimed to explore the molecular mechanisms whereby high glucose (HG)­induced lncRNA MIR181A2HG modulates human umbilical vein endothelial cell (HUVEC) proliferation and migration by regulating AKT2 expression. The persistent exposure of HUVECs to HG resulted in MIR181A2HG downregulation and thus reduced its ability to sponge miR­6832­5p, miR­6842­5p and miR­8056, subsequently leading to an increase in miR­6832­5p, miR­6842­5p and miR­8056 levels. Mechanistically, miR­6832­5p, miR­6842­5p and miR­8056 were found to target the 3'UTR of AKT2 mRNA in HUVECs, and the increase in their levels led to a decreased expression of AKT2. Thus, this also led to the suppression of HUVEC proliferation and migration, and the formation of capillary­like structures. Moreover, the suppression of HUVEC proliferation and migration induced by MIR181A2HG downregulation was accompanied by changes in glucose metabolism. On the whole, the present study demonstrates that the downregulation of lncRNA MIR181A2HG by HG impairs HUVEC proliferation and migration by dysregulating the miRNA/AKT2 axis. The MIR181A2HG/miRNA/AKT2 regulatory axis may thus be a potential therapeutic target for HG­induced endothelial dysfunction.


Assuntos
Movimento Celular/efeitos dos fármacos , Regulação para Baixo/genética , Glucose/toxicidade , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/genética , Regiões 3' não Traduzidas/genética , Sequência de Bases , Capilares/efeitos dos fármacos , Capilares/crescimento & desenvolvimento , Proliferação de Células/efeitos dos fármacos , Glucose/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Modelos Biológicos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo
14.
Int J Mol Med ; 47(4): 1, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33537830

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor in the human digestive system, which affects the physical and mental health of the patient. Long non­coding (lnc)RNAs have been revealed to play an important role in human malignant tumors. Moreover, long intergenic non­protein coding RNA 491 (LINC00491) is a newly discovered lncRNA that can affect the prognosis of cancer. The present study aimed to explore the expression of LINC00491 in ESCC tissues and cells. The reverse transcription­quantitative PCR results suggested that LINC00491 was upregulated in ESCC tissues and cells. LINC00491 expression in esophageal squamous cell carcinoma cells were knocked down. Cell Counting Kit­8, wound healing, Transwell and apoptosis assays were performed to detect the effects of LINC00491 knockdown on cell biological behavior. The results showed that lower expression of LINC00491 resulted in decreased cell proliferation and migration and increased the apoptosis rate. Therefore, the present results indicated that lncRNA LINC00491 promoted the biological processes of ESCC, and thus LINC00491 may be a potential therapeutic target for ESCC.


Assuntos
Apoptose/genética , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Inativação Gênica , Humanos , Invasividade Neoplásica , Metástase Neoplásica , RNA Longo não Codificante/genética , Cicatrização
15.
Int J Mol Med ; 47(4): 1, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33537835

RESUMO

Metastasis is the primary cause of the high mortality rates in head and neck squamous cell carcinoma (HNSCC). MicroRNA (miR)­411­5p has been discovered to serve an important role in cancer metastases. However, to the best of our knowledge, the association between miR­411­5p expression levels and HNSCC metastasis has not been thoroughly investigated. The present study aimed to research the function of miR­411­5p in HNSCC metastasis. The results of the present study revealed that miR­411­5p expression levels were upregulated in patients with HNSCC with lymph node metastasis and the upregulated expression levels of miR­411­5p were positively associated with the metastatic potential of HNSCC. Moreover, miR­411­5p promoted HNSCC cell migration, invasion and epithelial­mesenchymal transition (EMT). The results of the dual­luciferase reporter assays identified RING1 and YY1 binding protein (RYBP) as a functional downstream target gene for miR­411­5p. Therefore, whether miR­411­5p downregulated the expression levels of RYBP in HNSCC cells was subsequently investigated. Notably, the silencing of RYBP expression restored the stimulatory effects of miR­411­5p on HNSCC cell migration, invasion and EMT. In addition, the mRNA expression levels of miR­411­5p and RYBP were found to be inversely correlated in HNSCC samples. In conclusion, the results of the present study indicated that the miR­411­5p­mediated downregulation of RYBP expression levels may exert an important role in HNSCC metastasis and may provide a novel target for the treatment of HNSCC.


Assuntos
Metástase Linfática/genética , MicroRNAs/genética , Proteínas Repressoras/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Regulação para Cima/genética , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Metástase Linfática/patologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Proteínas Repressoras/genética
17.
Nat Commun ; 12(1): 757, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536423

RESUMO

Chordoma is a rare bone tumor with an unknown etiology and high recurrence rate. Here we conduct whole genome sequencing of 80 skull-base chordomas and identify PBRM1, a SWI/SNF (SWItch/Sucrose Non-Fermentable) complex subunit gene, as a significantly mutated driver gene. Genomic alterations in PBRM1 (12.5%) and homozygous deletions of the CDKN2A/2B locus are the most prevalent events. The combination of PBRM1 alterations and the chromosome 22q deletion, which involves another SWI/SNF gene (SMARCB1), shows strong associations with poor chordoma-specific survival (Hazard ratio [HR] = 10.55, 95% confidence interval [CI] = 2.81-39.64, p = 0.001) and recurrence-free survival (HR = 4.30, 95% CI = 2.34-7.91, p = 2.77 × 10-6). Despite the low mutation rate, extensive somatic copy number alterations frequently occur, most of which are clonal and showed highly concordant profiles between paired primary and recurrence/metastasis samples, indicating their importance in chordoma initiation. In this work, our findings provide important biological and clinical insights into skull-base chordoma.


Assuntos
Cordoma/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Proteína SMARCB1/genética , Neoplasias da Base do Crânio/genética , Fatores de Transcrição/genética , Sequenciamento Completo do Genoma/métodos , Adulto , Cordoma/patologia , Variações do Número de Cópias de DNA , Feminino , Genômica/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Neoplasias da Base do Crânio/patologia , Adulto Jovem
18.
Nat Commun ; 12(1): 773, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536439

RESUMO

Macrophages are plastic and, in response to different local stimuli, can polarize toward multi-dimensional spectrum of phenotypes, including the pro-inflammatory M1-like and the anti-inflammatory M2-like states. Using a high-throughput phenotypic screen in a library of ~4000 FDA-approved drugs, bioactive compounds and natural products, we find ~300 compounds that potently activate primary human macrophages toward either M1-like or M2-like state, of which ~30 are capable of reprogramming M1-like macrophages toward M2-like state and another ~20 for the reverse repolarization. Transcriptional analyses of macrophages treated with 34 non-redundant compounds identify both shared and unique targets and pathways through which the tested compounds modulate macrophage activation. One M1-activating compound, thiostrepton, is able to reprogram tumor-associated macrophages toward M1-like state in mice, and exhibit potent anti-tumor activity. Our compound-screening results thus help to provide a valuable resource not only for studying the macrophage biology but also for developing therapeutics through modulating macrophage activation.


Assuntos
Anti-Inflamatórios/farmacologia , Produtos Biológicos/farmacologia , Ensaios de Triagem em Larga Escala/métodos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Produtos Biológicos/química , Linhagem Celular Tumoral , Células Cultivadas , Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Humanos , Macrófagos/classificação , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Experimentais/prevenção & controle , Fenótipo , Células THP-1 , Tioestreptona/química , Tioestreptona/farmacologia
19.
Nat Commun ; 12(1): 769, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536445

RESUMO

Some breast tumors metastasize aggressively whereas others remain dormant for years. The mechanism governing metastatic dormancy remains largely unknown. Through high-parametric single-cell mapping in mice, we identify a discrete population of CD39+PD-1+CD8+ T cells in primary tumors and in dormant metastasis, which is hardly found in aggressively metastasizing tumors. Using blocking antibodies, we find that dormancy depends on TNFα and IFNγ. Immunotherapy reduces the number of dormant cancer cells in the lungs. Adoptive transfer of purified CD39+PD-1+CD8+ T cells prevents metastatic outgrowth. In human breast cancer, the frequency of CD39+PD-1+CD8+ but not total CD8+ T cells correlates with delayed metastatic relapse after resection (disease-free survival), thus underlining the biological relevance of CD39+PD-1+CD8+ T cells for controlling experimental and human breast cancer. Thus, we suggest that a primary breast tumor could prime a systemic, CD39+PD-1+CD8+ T cell response that favors metastatic dormancy in the lungs.


Assuntos
Antígenos CD/imunologia , Apirase/imunologia , Neoplasias da Mama/imunologia , Linfócitos T CD8-Positivos/imunologia , Neoplasias Mamárias Experimentais/imunologia , Receptor de Morte Celular Programada 1/imunologia , Animais , Antígenos CD/metabolismo , Apirase/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Humanos , Imunoterapia , Pulmão/imunologia , Pulmão/patologia , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/terapia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos Knockout , Metástase Neoplásica , Receptor de Morte Celular Programada 1/metabolismo
20.
BMJ Case Rep ; 14(2)2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547099

RESUMO

Patients with symptomatic complex malignant pleural effusion (MPE) are frequently unfit for decortication and have a poorer prognosis. Septations can develop in MPE, which may lead to failure of complete drainage and pleural infection. Intrapleural fibrinolytic therapy (IPFT) is an alternative treatment. The use of IPFT in patients with anaemia and high risk for intrapleural bleeding is not well established. We report a successful drainage of complex haemoserous MPE with a single modified low-dose of intrapleural 5 mg of alteplase and 5 mg of dornase alfa in a patient with pre-existing anaemia with no significant risk of intrapleural bleeding.


Assuntos
Desoxirribonuclease I/uso terapêutico , Derrame Pleural Maligno/terapia , Ativador de Plasminogênio Tecidual/uso terapêutico , Adulto , Terapia Combinada , Drenagem , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Derrame Pleural Maligno/diagnóstico por imagem , Derrame Pleural Maligno/microbiologia , Proteínas Recombinantes/uso terapêutico
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