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1.
Respir Res ; 21(1): 62, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111211

RESUMO

BACKGROUND: This study was to investigate of the mechanism by which histone deacetylase (HDAC) 8 inhibitor ameliorated airway hyperresponsiveness (AHR) and allergic airway inflammation. METHODS: Mice were sensitized and then treated with budesonide (BUD) or PCI-34051 (PCI) prior to exposing to normal saline (NS) or ovalbumin (OVA). The raw264.7 cells were treated with interleukin (IL)-4 and PCI or shRNA alone. Repetitive measurements of enhanced pause (Penh) were executed by increasing concentrations of acetyl-ß-methacholine chloride (0 - 50 mg/ml). Cells in bronchoalveolar lavage fluid (BALF) and pathological changes of lungs were examined, respectively. The expression levels of HDAC8, Galecitn (Gal)-3, CD68, CD86, CD163, Arg1 and NOS2 in lungs were measured. Co-regulation of HDAC8 and Gal-3 proteins was observed by immunofluorescence staining and co-immunoprecipitation assay (Co-IP). RESULTS: Significant increases in Penh and IL-4 level were detected with a large inflammatory infiltrate, comprised predominantly of macrophages and eosinophils, into the BALF in OVA-exposed lungs. HDAC8, Gal-3, CD68, CD86, CD163, Arg1 and NOS2 proteins were over-expressed with the significant changes in the Arg1 and NOS2 mRNA levels in the lungs and the IL-4-treated cells. PCI intervention obviously reduced the counts of CD163+ cells. Furthermore, Gal-3 knockdown suppressed Arg1 expression in the cells. Immunofluorescence staining displayed simultaneous changes in HDAC8 and Gal-3 expression in the investigated samples. Treatment with PCI resulted in synchronous reduction of HDAC8 and Gal-3 expression in the Co-IP complexes. CONCLUSIONS: The HDAC8 inhibitor ameliorates AHR and airway inflammation in animal model of allergic asthma through reducing HDAC8-Gal-3 interaction and M2 macrophage polarization.

2.
Biochem Biophys Res Commun ; 509(2): 407-413, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30594391

RESUMO

BACKGROUND: The forkhead activin signal transducer 1 (FAST1) is involved in several oncogenic signaling pathways and its abnormal expression has been discovered in some cancers. Yet the role of FAST1 in colorectal cancer (CRC) remains largely unclear. Therefore, the goal of this study was to explore the function of FAST1 in CRC. METHODS: In this study, we analyzed FAST1 expression and its relationship with clinicopathological parameters and prognostic significance in CRC via immunohistochemistry analysis. The effects and mechanisms of FAST1 on cell proliferation, migration and invasion were explored in vitro and in vivo. RESULTS: We found that increased FAST1 as an independent prognostic factor was positively associated with TNM stage and pathological grade in CRC. FAST1 overexpression promoted the CRC cell proliferation, migration and invasion in vivo. Furthermore, mechanistic studies implicated that FAST1 enhanced the pulmonary metastasis of CRC cells through down-regulating E-cadherin levels. CONCLUSIONS: In summary, FAST1 was significantly associated with CRC progression and could serve as an independent prognostic factor. FAST1 may be potential therapeutic target for CRC patients.


Assuntos
Neoplasias Colorretais/genética , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Idoso , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Caderinas/genética , Caderinas/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Células HCT116 , Xenoenxertos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Transdução de Sinais , Análise de Sobrevida
3.
Proc Natl Acad Sci U S A ; 115(50): E11661-E11670, 2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30478051

RESUMO

Long noncoding RNAs (lncRNAs) function through a diverse array of mechanisms that are not presently fully understood. Here, we sought to find lncRNAs differentially regulated in cancer cells resistant to either TNF-related apoptosis-inducing ligand (TRAIL) or the Mcl-1 inhibitor UMI-77, agents that act through the extrinsic and intrinsic apoptotic pathways, respectively. This work identified a commonly up-regulated lncRNA, ovarian adenocarcinoma-amplified lncRNA (OVAAL), that conferred apoptotic resistance in multiple cancer types. Analysis of clinical samples revealed OVAAL expression was significantly increased in colorectal cancers and melanoma in comparison to the corresponding normal tissues. Functional investigations showed that OVAAL depletion significantly inhibited cancer cell proliferation and retarded tumor xenograft growth. Mechanically, OVAAL physically interacted with serine/threonine-protein kinase 3 (STK3), which, in turn, enhanced the binding between STK3 and Raf-1. The ternary complex OVAAL/STK3/Raf-1 enhanced the activation of the RAF protooncogene serine/threonine-protein kinase (RAF)/mitogen-activated protein kinase kinase 1 (MEK)/ERK signaling cascade, thus promoting c-Myc-mediated cell proliferation and Mcl-1-mediated cell survival. On the other hand, depletion of OVAAL triggered cellular senescence through polypyrimidine tract-binding protein 1 (PTBP1)-mediated p27 expression, which was regulated by competitive binding between OVAAL and p27 mRNA to PTBP1. Additionally, c-Myc was demonstrated to drive OVAAL transcription, indicating a positive feedback loop between c-Myc and OVAAL in controlling tumor growth. Taken together, these results reveal that OVAAL contributes to the survival of cancer cells through dual mechanisms controlling RAF/MEK/ERK signaling and p27-mediated cell senescence.


Assuntos
Senescência Celular/genética , Senescência Celular/fisiologia , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Sistema de Sinalização das MAP Quinases , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Xenoenxertos , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Camundongos Nus , Estabilidade Proteica , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-raf/genética , Proteínas Proto-Oncogênicas c-raf/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
4.
Helicobacter ; 23(3): e12486, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29656498

RESUMO

BACKGROUND: Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori-induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication. MATERIALS AND METHODS: Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, and intestinal-type gastric cancer groups. Helicobacter pylori infection was determined by either 13 C-urea breath test or immunohistochemistry staining. RESULTS: In Helicobacter pylori-negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low-grade intraepithelial neoplasia, and declined in high-grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori-infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori-negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori-negative control. Labeling index of Ki67 in Helicobacter pylori-negative groups was higher in gastric cancer than chronic atrophic gastritis and low-grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori-positive groups, Ki67 labeling index was increased stepwise from nonatrophic gastritis to gastric cancer except slightly decrease in chronic atrophic gastritis group. In addition, we noted that histone H3 serine 10 phosphorylation staining is accompanied with its location changes from gastric gland bottom expanded to whole gland as disease stage progress. CONCLUSIONS: These results indicate that stepwise gastric carcinogenesis is associated with altered histone H3 serine 10 phosphorylation, Helicobacter pylori infection enhances histone H3 serine 10 phosphorylation expression in these processes; it is also accompanied with histone H3 serine 10 phosphorylation location change from gland bottom staining expand to whole gland expression. The results suggest that epigenetic dysregulation may play important roles in Helicobacter pylori-induced gastric cancer.


Assuntos
Carcinogênese/patologia , Infecções por Helicobacter/patologia , Histonas/metabolismo , Fosforilação/fisiologia , Gastropatias/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/metabolismo , Feminino , Infecções por Helicobacter/complicações , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Coloração e Rotulagem/métodos , Estômago/patologia , Gastropatias/metabolismo , Gastropatias/microbiologia , Adulto Jovem
5.
J Cancer Res Ther ; 14(1): 78-83, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29516964

RESUMO

Background: Glioblastoma (GBM) is one of the worst cancers with bad prognosis despite systemic chemotherapy and radiotherapy after surgery. Methods: In this study, 71 patients with GBM were enrolled and randomly assigned to two groups: Receiving radiotherapy with concomitant and adjuvant temozolomide (TMZ) (TMZ, standard therapy) after surgery, or receiving radiotherapy with concomitant and adjuvant local delivery of nimustine (ACNU) rendezvousing with oral TMZ (rendezvous therapy). In the follow-up of all patients and the progression-free survival (PFS), overall survival (OS), Karnofsky performance score (KPS) and toxicities were recorded. Results: For the whole cohort, the median OS was 18.0 months, and the median PFS was 7.8 months. A significantly longer OS was observed in patients received rendezvous therapy than those who receiving standard therapy (18.5 months vs. 16.0 months; P = 0.014), as well as PFS (8.8 months vs. 7.0 months; P = 0.008). The KPS ≥70 rates were 81.8%, 40.9%, 20.5% in 1, 2, and 3 years for the rendezvous therapy group, significantly superior to standard therapy group. The most common toxicities were tolerable gastrointestinal reaction, liver dysfunction, and hematological toxicities, which were relieved with symptomatic treatment. Grade 3 or 4 toxicity was documented in 8 (18.3%) patients in rendezvous therapy group, while it was observed in 6 (22.2%) patients in standard therapy group during whole treatment process. Conclusions: Compared to standard therapy, the antitumor effects of rendezvous therapy were more effective in GBM patients without increasing the toxicities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Terapia Combinada , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Feminino , Seguimentos , Glioblastoma/diagnóstico , Glioblastoma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nimustina/administração & dosagem , Modelos de Riscos Proporcionais , Qualidade de Vida , Radioterapia/efeitos adversos , Radioterapia/métodos , Temozolomida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
6.
Am J Transl Res ; 9(1): 103-114, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28123637

RESUMO

miR-34a is an important molecule that can inhibit the tumor growth. This study aimed to investigate the functional role of miR-34a in hepatocellular carcinoma (HCC) and explore the interaction between miR-34a and histone deacetylase 1 (HDAC1). RT-qPCR was employed to detect the mRNA expression of miR-34a and HDAC1 in 60 HCC tissues. Results showed miR-34a expression in HCC tissues was significantly lower than in normal tissues (P<0.05), but HDAC1 expression in HCC tissues was markedly higher than in normal tissues (P<0.05). In addition, miR-34a expression was negatively related to HDAC1 expression. miR-34a mimic was transfected into HCC cell lines (HepB3 and HepG2). CCK8 assay, colony formation assay and flow cytometry showed miR-34a over-expression could inhibit the proliferation of HCC cells and induce their apoptosis. Western blotting indicated miR-34a over-expression down-regulated the expression of Bcl-2, procaspase-3, procaspase-9 and c-Myc, but up-regulate p21 expression. Bioinformatics analysis indicated HDAC1 was a target gene of miR-34a. Dual Luciferase Reporter Gene Assay and retrieval assay showed miR-34a could act at the 3'UTR of HDAC1 gene to regulate its expression. Thus, miR-34a may inhibit the proliferation of HCC cells and induce their apoptosis via regulating HDAC1 expression. Our findings provide evidence for the diagnosis and therapeutic target of HCC.

7.
Am J Transl Res ; 8(2): 1037-46, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27158389

RESUMO

MicroRNAs (miRNA) play important regulatory roles in the occurrence and development of cancers. This study aimed to investigate the effects of miR-26a on the proliferation and apoptosis of ovarian cancer cells and explore the potential mechanism. qRT-PCR was performed to measure the miR-26a expression in 46 ovarian cancer tissues, and results showed miR-26a expression reduced significantly when compared with normal ovarian tissues (P<0.05). Moreover, miR-26a expression was related to the extent of cell differentiation and clinical stage of ovarian cancer (P<0.05). miR-26a mimic was transfected into SKOV3 cells and ES2 cells, and CCK8 assay, colony formation assay and flow cytometry showed miR-26a over-expression could significantly inhibit the proliferation of ovarian cancer cells and induce their apoptosis. Bioinformatics analysis revealed Cdc6 was a target gene of miR-26a. dual-luciferase assay and validation assay showed miR-26a could act on the 3'UTR of Cdc6 to regulate Cdc6 expression. These findings suggest that miR-26a may act on the 3'UTR of Cdc6 to regulate Cdc6 expression, which then inhibit the proliferation of ovarian cancer cells and induce their apoptosis. Our findings provide a new target for the diagnosis and therapy of ovarian cancer.

8.
World J Clin Cases ; 4(4): 118-23, 2016 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-27099863

RESUMO

Gastrointestinal (GI) stromal tumor is the most common mesenchymal neoplasm of the GI tract but also occurs with a lower frequency in extragastrointestinal regions and is called extragastrointestinal stromal tumor (EGIST). We report an unusual case of EGIST presenting as a vaginal mass. A 41-year-old woman presented with a gradually enlarging vaginal mass for the last 2 years. Physical examination revealed an elliptical, non-tender mass about 7.5 cm × 7 cm in size in the posterior vaginal wall and was resected completely. Under histological examination, the tumor showed a spindle cell type with coagulation necrosis, hemorrhage and high mitotic count. Immunohistochemical analysis revealed tumor cells were positive for DOG1, CD117, CD34 and p53 protein. Ki-67 labeling was 8%. Genetic analysis showed a deletion of exon 11 of the c-kit gene at codons 557-558. EGISTs should be kept in mind in the differential diagnosis in patients presenting with solid mass of the vaginal wall.

9.
Acta Neurochir (Wien) ; 158(4): 695-702, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26899971

RESUMO

BACKGROUND: Papillary glioneuronal tumor (PGNT) is a rare, recently described distinct low-grade brain neoplasm. This study was performed to characterize the clinicopathologic and neuroradiologic features of PGNTs. METHODS: We reviewed the medical records of 16 patients with PGNT who underwent surgery, including 11 males and five females (median age 27 years). The clinical, neuroradiologic, histopathologic, and immunohistochemical findings were documented. RESULTS: Headache was the principal presentation. Neuroimaging showed contrast-enhancing, cystic-solid or cystic masses with a mural nodule, mostly involved the frontal or parietal lobes. Histologically, the tumors were characterized by glial fibrillary acidic protein (GFAP)-positive small cuboidal cells lining hyalinized vascular pseudopapillae and synaptophysin and/or NeuN-positive interpapillary neuronal elements. Other findings included small angiomatous areas in ten, small islands of neuropil and rosettes in seven, and microvascular proliferation and/or nuclear atypia in six. Mitoses or necrosis were absent. All lacked isocitrate dehydrogenase 1 (IDH1) R132H protein expression. Low expression of p53 was observed in three cases. Ki67 labeling index ranged from less than 1 to 3 %. All but one was totally resected. Median follow-up was 65 months, and one patient had tumor recurrence. CONCLUSIONS: PGNTs display distinct clinicopathologic and imaging characteristics and indicate a favorable prognosis. However, recurrences sometimes occur. Immunohistochemistry facilitates the appropriate diagnosis of these tumors. Complete resection of the tumor is important for a favorable outcome.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Imagem por Ressonância Magnética , Neoplasias Neuroepiteliomatosas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Neoplasias Encefálicas/patologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Neuroepiteliomatosas/patologia , Oligodendroglia/patologia
10.
Int J Clin Exp Med ; 8(8): 13388-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26550271

RESUMO

OBJECTIVE: This study aimed to investigate expression level of FOXC2 and its relationship to clinical pathological features of renal cell carcinoma (RCC). METHODS: The expression levels of FOXC2 in RCC tissues and normal renal tissues (62 samples, respectively) were detected by immunohistochemistry and PCR Array. Statistics analyses were done with SPSS to compare the differences between RCC tissues and normal renal tissue, and to explore the relationship between the expression level of FOXC2 and the clinical pathological features of RCC. RESULTS: Expression level of FOXC2 in RCC tissues was significantly higher than in normal renal tissues, and other related cancer genes also highly expressed in RCC tissues. FOXC2 expression was positively associated with clinical stage and pathological grade (P < 0.05), but not significantly related to the gender and age (P > 0.05). CONCLUSION: The expression of FOXC2 in renal cell carcinoma was significantly higher than that in normal renal tissues. It is suggested that FOXC2 might play a crucial role in the occurrence and development of RCC and could be an important prognostic indicator for clinical therapy.

11.
J Child Neurol ; 30(5): 631-4, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23965399

RESUMO

Melanotic neuroectodermal tumor of infancy is a rare melanin-containing neoplasm with locally aggressive and rapid expansile growth, usually involving the maxilla, skull, and mandible of early infancy. Radical surgery is critical for a long-term outcome. We present a case of 14-month-old girl with rapid-growing subcutaneous mass arising in the right temporal bone and extending intracranially on computed tomographic scan. Radical surgery was performed. A brownish-black tumor composed of large pigmented epithelioid cells, positive for cytokeratins and HMB-45, and nests of small neuroblast-like cells positive for neuron-specific enolase and synaptophysin, was diagnosed as melanotic neuroectodermal tumor of infancy. The patient remained well without evidence of recurrence for 1 year after surgery. Clinicopathological features, management alternatives and outcome were discussed.


Assuntos
Tumor Neuroectodérmico Melanótico/diagnóstico por imagem , Tumor Neuroectodérmico Melanótico/cirurgia , Neoplasias Cranianas/diagnóstico por imagem , Neoplasias Cranianas/cirurgia , Osso Temporal/diagnóstico por imagem , Osso Temporal/cirurgia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Lactente , Tumor Neuroectodérmico Melanótico/diagnóstico , Tumor Neuroectodérmico Melanótico/patologia , Neoplasias Cranianas/diagnóstico , Neoplasias Cranianas/patologia , Osso Temporal/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
J Child Neurol ; 30(8): 1017-23, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25323739

RESUMO

Atypical teratoid/rhabdoid tumors are rare malignant pediatric brain tumors. This study was performed to characterize the clinicopathologic and neuroradiologic characteristics of atypical teratoid/rhabdoid tumors from 8 patients, including 5 male and 3 female infants (median age, 67 months). Neuroimaging revealed bulky masses of heterogeneous intensity with inhomogeneous enhancement. Three cases were infratentorial and 5 were supratentorial. Histopathologically, the tumors were predominantly composed of rhabdoid cells and undifferentiated small cells, mixed with some spindle or epithelial components. The tumors displayed striking polyphenotypic immunoreactivity, including varying degrees of positivity for vimentin, epithelial membrane antigen, smooth-muscle actin, cytokeratin, glial fibrillary acidic protein, neurofilament protein, synaptophysin, and CD99, and immunonegativity for desmin, placental alkaline phosphatase, and INI-1. The median survival duration was 9.5 months (range, 1-15 months) despite aggressive therapy. These results suggest that atypical teratoid/rhabdoid tumors display distinct clinicopathologic characteristics and indicate a poor prognosis. Immunohistochemistry facilitates the appropriate diagnosis of these tumors.


Assuntos
Neoplasias Encefálicas , Tumor Rabdoide , Teratoma , Antígeno 12E7 , Adolescente , Antígenos CD/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Moléculas de Adesão Celular/metabolismo , Criança , Pré-Escolar , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Lactente , Queratinas/metabolismo , Masculino , Mucina-1/metabolismo , Estudos Retrospectivos , Tumor Rabdoide/diagnóstico por imagem , Tumor Rabdoide/metabolismo , Tumor Rabdoide/patologia , Proteína SMARCB1 , Teratoma/diagnóstico por imagem , Teratoma/metabolismo , Teratoma/patologia , Tomografia Computadorizada por Raios X , Fatores de Transcrição/metabolismo , Adulto Jovem
14.
Iran J Basic Med Sci ; 17(9): 710-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25691949

RESUMO

OBJECTIVES: The present study was aimed to investigate the influence of thoracic epidural blockade on hypoxia-induced pulmonary hypertension in rats. MATERIALS AND METHODS: Forty eight Wistar rats were randomly divided into 4 equal groups, named normoxia hypoxia hypoxia/ ropivacaine and hypoxia/saline. Animals were placed in a hypoxia chamber and instrumented with epidural catheters at the thoracic level. Rats were injected with saline or ropivacaine. Haemodynamic measurements included pulmonary artery pressure and right ventricular hypertrophy. Degree of pulmonary vascular remodeling was determined by Hematoxylin and Eosin (HE) staining. Serum cyclic GMP (cGMP) and TNF-α were measured using radioimmuno assay. Real-time PCR and western boltting were employed to examine the expression of cAMP responding-element binding protein (CREB). RESULTS: We found that the thoracic epidural blockade significantly decreased chronic hypoxia-induced pulmonary hypertension and vascular remodeling in rats. Ropivacaine-treated rats exhibited significantly lower mean pulmonary artery pressure (mPAP), ratio of right ventricular weight to left ventricular plus septal weight (RV/(LV+S)) and wall thickness of pulmonary artery compared with those of control rats. Hypoxia-induced increase in levels of serum cGMP and TNF-α was reversed by thoracic epidural blockade. Moreover, hypoxia increased expression of CREB at mRNA and protein levels which could be suppressed by thoracic epidural blockade. CONCLUSION: Thoracic epidural blockade reduced mPAP and serum level of TNF-α and increased cGMP. The treatment reversed upregulated expression of CREB at mRNA and protein production.

15.
J Child Neurol ; 29(11): 1441-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23752069

RESUMO

Dysembryoplastic neuroepithelial tumors are rare, surgically curable, neuronal-glial neoplasms affecting young patients with intractable epilepsy. Its recognition is needed to avoid unnecessary adjuvant therapy. The authors reviewed the records of 15 patients with dysembryoplastic neuroepithelial tumors who underwent epilepsy surgery using intraoperative electrocorticography monitoring, including 8 males and 7 females (mean age, 15.8 years). Neuroimaging showed a predominantly intracortical location, the presence of septations, a triangular pattern of distribution, a lack of contrast enhancement, and an absence of peritumoral edema. Eleven cases were classified as complex type, 3 as simple type, and 1 as "nonspecific" type. Associated cortical dysplasia was found in 5 cases and leptomeningeal involvement in 1 case. Its immunophenotype suggested a pluripotential neuroepithelial origin. The mean follow-up was 37.5 months; 2 patients had tumor recurrence. Although they are generally benign neoplasms, recurrences sometimes occur. Complete resection of the tumor with the epileptogenic zone is important for a favorable outcome.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Neoplasias Neuroepiteliomatosas/patologia , Neoplasias Neuroepiteliomatosas/fisiopatologia , Adolescente , Adulto , Edema Encefálico/fisiopatologia , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , Epilepsia/fisiopatologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Imagem por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia , Neoplasias Neuroepiteliomatosas/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
16.
Ann Med ; 46(1): 24-30, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24328420

RESUMO

OBJECTIVES: This meta-analysis aimed to compare the treatment of an acute asthma attack in children in the emergency department (ED) with inhaled corticosteroids (ICS) versus placebo or oral systemic corticosteroids (SC) as assessed by the hospital admission rates. METHODS: After searching Medline, Cochrane, EMBASE, and Google Scholar, we identified ten articles that described randomized controlled trials of ICS versus placebo or oral SC for treating children with asthma attacks in the ED. Primary outcome was the hospital admission rate as defined as inpatient admission or admission into intensive care unit. RESULTS: Across the studies, a range of drugs and doses were used. For ICS, six studies administered budesonide (dose range: 0.4-2 mg), and three studies gave fluticasone/flunisolide (dose range: 0.5-2 mg). Six studies administered oral prednisone (dose range: 1-2 mg/kg/day), and four studies gave placebo. The rate of hospital admissions in patients treated with ICS was not significantly higher than those treated with oral SC. The rate of hospital admissions in patients treated with ICS was significantly lower than those treated with placebo. CONCLUSION: ICS treatment of children with acute asthma exacerbations showed a similar rate of hospitalization as those treated by SC.


Assuntos
Corticosteroides/administração & dosagem , Asma/tratamento farmacológico , Serviço Hospitalar de Emergência , Doença Aguda , Administração por Inalação , Administração Oral , Criança , Testes Diagnósticos de Rotina , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Zhonghua Nei Ke Za Zhi ; 52(8): 651-3, 2013 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-24199879

RESUMO

OBJECTIVE: To investigate the prevalence of occupational asthma, airway inflammation and analyze the risk factors for workers exposed to isocyanates. METHODS: A cross-sectional study was applied. Totally 429 isocyanates exposed workers were surveyed and the prevalence of occupational asthma and airway inflammation situation were examined by questionnaire, physical examination and laboratory tests. Multivariate logistic regression was applied to analyze the possible risk factors of isocyanate-induced occupational asthma. RESULTS: (1) A total of 366 patients with complete data were included in the study, and finally 11 cases were diagnosed as isocyanate-induced occupational asthma with a prevalence of 3.0%. (2) Neutrophil percentage in the induced sputum of occupational asthma increased significantly [42.00% (34.00%-55.00%) before work and 59.00% (51.00%-70.00%) after work (Z = -2.940. P < 0.05)]. (3) Length of service (OR = 3.096, P = 0.025) and rhinitis (OR = 1.901, P = 0.008) were independent dangerous factors, and protective measures (OR = 0.074, P = 0.015) was protective factors to isocyanate-induced occupational asthma. CONCLUSIONS: Neutrophilic inflammation can be triggered by isocyanate exposure. Regular health examinations, effective protective measures can reduce the prevalence of isocyanate-induced occupational asthma.


Assuntos
Asma Ocupacional/etiologia , Isocianatos/efeitos adversos , Exposição Ocupacional/efeitos adversos , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
18.
Zhonghua Bing Li Xue Za Zhi ; 41(8): 534-7, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23157745

RESUMO

OBJECTIVE: To study the clinicopathologic features, radiologic findings, treatment options and prognosis of dysembryoplastic neuroepithelial tumor (DNT). METHODS: The clinicopathologic and radiologic features were retrospectively analyzed in 10 cases of DNT. RESULTS: Intractable partial seizure was the main presenting symptom in all patients. The tumor was located in temporal lobe (number = 5), frontal lobe (number = 3) or parietal lobe (number = 2). CT scan displayed a hypodense lesion. MRI scan revealed the tumor was non-enhancing T1WI hypointense and T2WI hyperintense, with internal septation and hyperintense ring around the tumor seen on FLAIR image. There was neither peritumoral edema nor mass effect. Histologically, the tumor showed the presence of glioneuronal element, with oligodendrocyte-like cells, floating neurons, astrocytes and associated microcystic changes. Immunohistochemical study demonstrated positivity for NeuN and synaptophysin in the neurons and some oligodendrocyte-like cells. Olig2 and S-100 protein were also expressed in the oligodendrocyte-like cells. Ki-67 index were lower than 1% in all cases. Nine cases were treated by complete surgical excision and the remaining case was subtotally excised. No post-operative chemotherapy or radiotherapy was given. One of the 10 cases recurred on follow up. CONCLUSIONS: Correct diagnosis of DNT requires correlation with clinicopathologic, radiologic and immunohistochemical findings. Complete resection of the tumor and epileptogenic foci is the mainstay of treatment for DNT, with intraoperative EEG monitoring. Post-operative chemotherapy or radiotherapy is not required.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Neuroepiteliomatosas/patologia , Adolescente , Adulto , Antígenos Nucleares/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirurgia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Criança , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Neoplasias Neuroepiteliomatosas/diagnóstico , Neoplasias Neuroepiteliomatosas/metabolismo , Neoplasias Neuroepiteliomatosas/cirurgia , Proteínas do Tecido Nervoso/metabolismo , Procedimentos Neurocirúrgicos , Fator de Transcrição 2 de Oligodendrócitos , Estudos Retrospectivos , Proteínas S100/metabolismo , Sinaptofisina/metabolismo , Tomografia Computadorizada por Raios X , Adulto Jovem
19.
Zhonghua Nei Ke Za Zhi ; 50(8): 672-5, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-22093560

RESUMO

OBJECTIVE: To constitute a correlation with the subjective indicators by investigation of the causes and clinical features in patients with chronic cough. METHODS: Totally 100 patients with chronic cough were recruited followed a diagnostic program. Airway responsiveness [by methacholine challenge test (MCT)], Leicester cough questionnaire (LCQ), visual analogue scale (VAS), cough score, age, gender and disease duration were all recorded for analysis. RESULTS: The top five causes of chronic cough in these patients were variant asthma, post infectious cough, atopic cough, eosinophilic bronchitis and upper airway cough syndrome. LCQ total score was negatively correlated with age and the VAS score (r = -0.239 and -0.470 respectively, all P < 0.05), while no difference was found among patients with different causes of disease or gender (F = 1.233, t = 1.918, all P > 0.05) and no correlation was found with BMI (r = -0.029, P > 0.05). The physiological and psychological field score in female patients significantly reduced (t = 2.174, 1.990, P < 0.05), and LCQ total score of MCT positive patients obviously reduced than negative ones (t = -2.22, P < 0.05). After the treatment of two weeks, LCQ three component field and total score could be improved significantly (all P < 0.01). CONCLUSIONS: Gender and age may have some impact on the quality of life in patients with chronic cough. LCQ, VAS and cough score should be used to assess cough severity and evaluate therapeutic effect in patients with chronic cough.


Assuntos
Tosse/psicologia , Qualidade de Vida , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Doença Crônica , Tosse/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Zhonghua Nei Ke Za Zhi ; 50(3): 221-4, 2011 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-21600086

RESUMO

OBJECTIVE: To observe sputum cytology counts, the levels of nerve growth factor (NGF) and IL-4 in cough variant asthma (CVA) patients and the change of their levels after using glucocorticoids combined with ß(2)-adrenergic agonists one month, and to investigate CVA's characteristics of airway inflammation. METHODS: Totally 36 patients with untreated CVA were selected, as well as 23 healthy controls. Coughed up sputum cells were obtained and HE strained for differential cell counting in each enrolled patient. In induced sputum's supernatant, the levels of NGF and IL-4 were determined by ELISA. RESULTS: Before treatment, CVA patients had a median eosinophils (EOS) percentage of 8%, which was significantly higher than that after treatment (2%, P < 0.05) and in healthy control group (1%, P < 0.001). The levels of NGF and IL-4 in induced sputum of CVA group were (9.50 ± 1.69) ng/L and (257.37 ± 53.57) ng/L. After treatment, they were (8.78 ± 1.02) ng/L and (228.60 ± 52.93) ng/L in CVA group, (6.98 ± 0.69) ng/L and (166.44 ± 24.75) ng/L in healthy control group. The levels of NGF and IL-4 before and after treatment in the CVA group, as compared with the healthy control group, had statistically significant differences (all P < 0.001). In CVA group before and after treatment, the level of NGF and IL-4 paired difference was significant (P < 0.001). The percentage of induced sputum EOS correlated with sputum supernatant concentrations of NGF and IL-4 (P < 0.01). In induced sputum supernatant, the concentrations of NGF and IL-4 were significant correlated (P < 0.01). CONCLUSIONS: Glucocorticoid joint long-term ß(2) agonist inhaled treatment significantly reduced NGF, IL-4 and EOS levels and reduced eosinophilic inflammation, which are closely related with the nerve-immune mechanism, NGF as well as IL-4 participated the inflammation. Induced sputum examination is non-invasive, economical, simple, easily accepted by patients, and repeatable, widely used in clinical.


Assuntos
Asma/metabolismo , Tosse/metabolismo , Interleucina-4/metabolismo , Fator de Crescimento Neural/metabolismo , Escarro/metabolismo , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Adulto , Asma/tratamento farmacológico , Asma/patologia , Estudos de Casos e Controles , Tosse/patologia , Eosinófilos/citologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Escarro/citologia , Adulto Jovem
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