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1.
Nanoscale ; 12(2): 1091-1099, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31845951

RESUMO

Photomultiplication (PM) type organic photodetectors (OPDs) based on electron tunneling injection are achieved with a specific structure of ITO/ZnO/PC71BM:P3HT (100 : 5, wt/wt)/Au and can work well under forward and reverse bias. A rather low dark current density of the PM type OPDs is obtained due to the large electron injection barrier of 0.7 eV from the ITO electrode or 1.1 eV from the Au electrode, as well as the absence of continuous hole transport channels in the active layers. The external quantum efficiency (EQE) spectral shape of PM type OPDs can be easily adjusted by altering the bias polarity and active layer thickness, which can be well explained by the trapped hole distribution near the ITO and Au electrodes, respectively. The PM type OPDs with 400 nm active layers exhibit the maximum EQE of 3900% and 4900% under 5 V and -5 V bias, respectively. This work firstly achieves PM type OPDs with electron-only transport properties, which has great potential to well match with other organic electronic devices.

2.
J Phys Chem Lett ; 11(2): 366-373, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31870156

RESUMO

Broad response organic photodetectors (OPDs) with a photomultiplication (PM) effect are achieved with one absorber layer and one multiplication layer. The response range of the PM-OPDs is primarily determined by materials in the absorber layer, and the external quantum efficiency (EQE) of the PM-OPDs is mainly controlled by the multiplication layer. Here, double-layered PM-OPDs were designed with an ITO/ZnO/PM6:Y6/PC71BM:P3HT (100:5, w/w)/Au structure, where PM6:Y6 is employed as an absorber layer and PC71BM:P3HT is used as a multiplication layer. The optimal PM-OPDs exhibit a broad response covering 350-950 nm. Meanwhile, the optimal PM-OPDs exhibit the largest EQE value of ∼1200% and a maximum specific detectivity (D*) of ∼6.8 × 10-12 cm Hz1/2 W-1 under a 10 V bias. This double-layered approach may be a smart strategy for realizing PM-OPDs with an easily adjustable response range.

3.
Front Cell Dev Biol ; 7: 217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632968

RESUMO

Background: LncRNAs have been shown to play essential roles in cancer therapeutic response. However, the detailed mechanism of lncRNAs in temozolomide (TMZ) resistance in glioblastoma (GBM) remain to be elucidated. Methods: To elucidate the mechanism maintaining TMZ resistance, we constructed two TMZ-resistant GBM cell lines (T98G-R/U118-R). LncRNAs from four public datasets were reanalyzed, and the candidate lncRNA ADAMTS9-AS2 was evaluated in TMZ-treated GBM patients and in vitro cell lines. Results: Reanalysis of lncRNA expression profiles identified ADAMTS9-AS2 as significantly overexpressed in TMZ-resistant GBM cells and as positively associated with the IC50 of TMZ in GBM cells. Overexpression of ADAMTS9-AS2 was also significantly associated with poor TMZ response and shorter progression-free survival (PFS) in TMZ-treated GBM patients. Knockdown of ADAMTS9-AS2 inhibited proliferation and attenuated the IC50 of TMZ, as well as mitigating invasion and migration in TMZ-resistant GBM cells. Subsequent investigations indicated that reduced expression of ADAMTS9-AS2 significantly suppressed expression of the FUS protein, which was predicted as a direct substrate of ADAMTS9-AS2. Expression trends of FUS were directly correlated with those of ADAMTS9-AS2, as shown by increasing concentrations and prolonged treatment with TMZ. RNA pull-down and RIP assays indicated that both endogenous and exogenous ADAMTS9-AS2 directly binds to the RRM and Znf_RanBP2 domains of FUS, consequently increasing FUS protein expression. Knockdown of ADAMTS9-AS2 reduced the half-life of FUS and decreased FUS protein stability via K48 ubiquitin degradation. Moreover, the E3 ubiquitin-protein ligase MDM2 interacts with and down regulates FUS, while the RRM and Znf_RanBP2 domains of FUS facilitate its binding with MDM2. ADAMTS9-AS2 decreased the interaction between MDM2 and FUS, which mediates FUS K48 ubiquitination. Additionally, knockdown of the ADAMTS9-AS2/FUS signaling axis significantly alleviated progression and metastasis in TMZ-resistant cells. Conclusion: ADAMTS9-AS2 possessed a novel function that promotes TMZ resistance via upregulating the FUS/MDM2 axis in GBM cells. The RRM or Znf_RanBP2 domains of FUS facilitate the combination of ADAMTS9-AS2 and FUS, competitively inhibiting MDM2-dependent FUS K48 ubiquitination and resulting in enhanced FUS stability and TMZ resistance. Our results suggest that the ADAMTS9-AS2/FUS/MDM2 axis may represent a suitable prognostic biomarker and a potential target in TMZ-resistant GBM therapy.

4.
Biomacromolecules ; 20(10): 3969-3979, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31536333

RESUMO

In this work, poly(vinyl alcohol) (PVA) biocomposites with regenerated cellulose-softwood pulp (RC-SP) as a green reinforcement were prepared via co-precipitation method. Simultaneous precipitation of the two components promotes uniform dispersion of the RC-SP and constructs strong molecular chain entanglements and hydrogen bonding network inside the composites. This physical cross-linking network reduces the water absorption and improves the water resistance of the composites. The incorporation of RC-SP not only improves the thermal decomposition properties of the composites, but also enhances the mechanical properties and dynamic mechanical properties, attributed to the strong interaction between the filler and the matrix. Moreover, the fabricated PVA/RC-SP composites exhibit good water-induced shape memory effect, and shape recovery rate of 10% RC-SP reinforced composite reaches 95.3% after immersing for 35 min. This work provides useful information for the implementation of co-precipitation method and the application of renewable cellulose resources.

5.
J Exp Clin Cancer Res ; 38(1): 171, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31014370

RESUMO

Cancer-associated fibroblasts (CAFs) plays an essential role in cancer cell growth, metabolism and immunoreaction. Autophagy is an intracellular self-degradative process that balances cell energy source and regulates tissue homeostasis. Targeting autophagy has gained interest with multiple preclinical and clinical trials, such as the pharmacological inhibitor chloroquine or the inducer rapamycin, especially in exploiting its ability to modulate the secretory capability of CAFs to enhance drug delivery or inhibit it to prevent its influence on cancer cell chemoresistance. In this review, we summarize the reports on autophagy in cancer-associated fibroblasts by detailing the mechanism and role of autophagy in CAFs, including the hypoxic-autophagy positive feedback cycle, the metabolic cross-talk between CAFs and tumors induced by autophagy, CAFs secreted cytokines promote cancer survival by secretory autophagy, CAFs autophagy-induced EMT, stemness, senescence and treatment sensitivity, as well as the research of antitumor chemicals, miRNAs and lncRNAs. Additionally, we discuss the evidence of molecules in CAFs that are relevant to autophagy and the contribution to sensitive treatments as a potential target for cancer treatment.


Assuntos
Autofagia/genética , Transformação Celular Neoplásica/genética , Neoplasias/genética , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , MicroRNAs/genética , Neoplasias/patologia , RNA Longo não Codificante/genética
7.
J Cancer ; 8(15): 2924-2932, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28928883

RESUMO

PURPOSE: AHNAK is originally identified as a giant protein based on the estimated size of approximately 700 kDa. The aim of this study is to identify the role of AHNAK in the pathogenesis of glioma. METHODS: We tested AHNAK mRNA level in a panel of six human glioma cell lines, and in 30 cases of normal brain tissues and 73 cases of glioma tissue samples using a qRT-PCR method. Further, we analyzed the relationship of AHNAK expression with clinicopathological characteristics in glioma patients. Meanwhile, we analyzed the relationship of expression of AHNAK and survival of glioma patients in survival analyses. Then, in vitro, we analyzed the biological effects of AHNAK in glioma cell lines (U87 and U251) including proliferation assay, cell transwell assay, and apoptosis. And in vivo, we examined the effects of AHNAK on tumor growth using xenograft model of human glioma cells in nude mice. Then we examined the expression of Ki-67-positive cells in these tumors. RESULTS: We found that the mRNA levels of AHNAK were down-regulated in 4 of 6 human glioma cell lines, especially in U87 and U251 cell lines. Meanwhile, in glioma patients, a negative correlation was found between the expression of AHNAK and the glioma histopathology. And a low expression of AHNAK was a significant and independent prognostic factor for poor survival of glioma patients. Through over expression of AHNAK in both of U87 and U251, we demonstrated that overexpression of AHNAK could inhibit glioma cell proliferation and invasion, induce apoptosis, and inhibit in vivo glioma tumor growth and ki-67 expression. CONCLUSIONS: The AHNAK acts as a potential tumor suppressor. Our study provides a preclinical basis for developing AHNAK as a reliable clinical prognostic indicator for glioma patients, and a new biomarker for treatment response, and a potentially therapeutic target in glioma management options.

8.
Biomed Res Int ; 2017: 8124501, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28421199

RESUMO

Valproic acid (VPA), a drug widely used to treat manic disorder and epilepsy, has recently shown neuroprotective effects in several neurological diseases, particularly in Parkinson's disease (PD). The goal of the present study was to confirm VPA's dose-dependent neuroprotective propensities in the MPP+ model of PD in primary dopamine (DA) neurons and to investigate the underlying molecular mechanisms using specific mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase- (PI3K-) Akt signaling inhibitors. VPA reversed MPP+-induced mitochondrial apoptosis and counteracted MPP+-induced extracellular signal-regulated kinase (ERK) and Akt repression and inhibited glycogen synthase kinase 3ß (GSK3ß) activation through induction of GSK3ß phosphorylation. Moreover, inhibitors of the PI3K and MAPK pathways abolished GSK3ß phosphorylation and diminished the VPA-induced neuroprotective effect. These findings indicated that VPA's neuroprotective effect in the MPP+-model of PD is associated with GSK3ß phosphorylation via Akt and ERK activation in the mitochondrial intrinsic apoptotic pathway. Thus, VPA may be a promising therapeutic candidate for clinical treatment of PD.


Assuntos
Apoptose/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Intoxicação por MPTP/prevenção & controle , Mitocôndrias/metabolismo , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ácido Valproico/farmacologia , Animais , Neurônios Dopaminérgicos/patologia , Feminino , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/patologia , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/patologia
9.
Cell Physiol Biochem ; 39(6): 2173-2185, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27802437

RESUMO

BACKGROUND: Valproic acid (VPA), an established antiepileptic drug, was assessed for antitumor activity, including its effects on glioblastoma, but its role has not been determined. METHODS: In the present study, we investigated VPA-induced apoptosis effects on human U87 cells by cell viability, lactate dehydrogenase (LDH) release, TUNEL/Hoechst staining and flow cytometric in vitro, then we further explored the underlying molecular mechanisms using the selective antagonists PD98059, LY294002 and SB216763. RESULTS: The data showed that VPA dose-dependent induction of glioma U87 cells to undergo apoptosis through the mitochondria-dependent pathway in vitro. VPA activated the ERK/Akt pathways by increasing their protein phosphorylation and in turn inhibited GKS3ß activation by the induction of GKS3ß phosphorylation. However, the MAPK inhibitor PD98059 and/or PI3K inhibitor LY294002 were able to antagonize the effects of VPA by abolishing ERK/Akt activations and cancelling GSK3ß suppression, thus it impaired VPA apoptosis-inducing effects on glioma cells. Furthermore, the GSK3ß inhibitor SB216763 caused a strong suppression of GSK3ß activity, which showed similar effects of VPA on regulation of protein expression and apoptosis. CONCLUSION: These findings suggest that GSK3ß may be the central hub for VPA-induced apoptosis and VPA can be further evaluated as a novel agent for glioma therapy.


Assuntos
Apoptose/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glioma/enzimologia , Glioma/patologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ácido Valproico/farmacologia , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Citometria de Fluxo , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Biológicos , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos
10.
Microrna ; 5(3): 222-229, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27855604

RESUMO

BACKGROUND: The diagnosis of ulcerative colitis (UC) or Crohn disease (CD) can be challenging given the overlapping features. Knowledge of microRNAs in IBD has expanded recently and supports that microRNAs play an important role. This study aimed to identify novel microRNA biomarkers through comprehensive genome-wide sequencing to distinguish UC from CD. DESIGN: Illumina next generation sequencing was performed on nondysplastic fresh-frozen colonic mucosa of the distal-most colectomy from 19 patients (10 UC and 9 CD) and 18 patients with diverticular disease serving as controls. RESULTS: USeq software package identified 44 microRNAs with altered expression (fold change ≥2 and false discovery rate ≤0.10) compared to controls. Among them, a panel of 11 microRNAs was aberrantly expressed between UC and CD. qRT-PCR validation assays performed on frozen tissue from additional samples of UC (n=20) and CD (n=10) confirmed specific differential expression of miR-147b, miR-194-2, miR-383, miR-615 and miR-1826 (P<0.05). In addition, pathway analysis identified target genes of epithelial adhesion junction, integrin, glycolysis and cell cycle that involve in signaling pathways of TGF-ß, STAT3, IL-8 and PI3L/AKT/mTOR. CONCLUSION: Identification of differentially expressed microRNAs in UC and CD supports the hypothesis that UC and CD are regulated by distinct pathophysiologic mechanisms. MicroRNA panels show promise as diagnostic biomarkers for the subtyping of inflammatory bowel disease.


Assuntos
Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética , Doença de Crohn/diagnóstico , Doença de Crohn/genética , MicroRNAs/genética , Adulto , Idoso , Sequência de Bases , Estudos de Casos e Controles , Colo/citologia , Colo/patologia , Diagnóstico Diferencial , Feminino , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mucosa Intestinal/citologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA
12.
Zhonghua Wai Ke Za Zhi ; 54(5): 367-71, 2016 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-27143207

RESUMO

OBJECTIVE: To investigate the indications of the pretemporal transcavernous approach for cavernous sinus tumors resection and design individually tailored surgery according to the extent of tumors and operation requirements. METHODS: A retrospective analysis of clinical data, surgical outcomes and complications in a series of 31 cases with cavernous sinus tumor operated via the individually tailored pretemporal transcavernous approach between May 2012 and September 2015 in Department of Neurosurgery, Xiangya Hospital, Central South University. There were 13 male and 18 female patients, aging from 17 to 67 years with a mean of (41±14) years. The patients included 18 cases of shwannomas, 4 cases of meningiomas, 3 cases of cavernous hemangiomas, 2 cases of invasive pituitary adenomas, 1 case of chordoma, 1 case of chondroma, 1 case of recurrent teratoma, 1 case of metastatic nasopharyngeal carcinoma. The first followed-up visit was on the 3(rd) month after surgery, and if tumor progression or recurrence was observed on MRI, the Gamma knife treatment was recommended, the patient was followed up every 6 months, otherwise the patient was followed up again 6 months later, then, every 12 months. RESULTS: Gross total removal of tumors was achieved in 22 cases of 31 patients (71.0%), containing 17 cases of shwannomas, 3 cases of hemangiomas, 1 case of chondroma, 1 case of teratoma; subtotal removal in 6 cases (19.3%), including 3 cases of meningiomas, 1 case of pituitary adenoma, 1 case of chordoma, 1 case of metastatic carcinoma; partial removal in 3 cases (9.7%), comprising 1 case of meningioma, 1 case of recurrent shwannoma, 1 case of recurrent pituitary adenoma. The symptoms of cranial never aggravated in 5 cases, the new postoperative cranial never palsy was observed in 7 cases. There was no surgical mortality, intracranial hematoma, intracranial infection and cerebrospinal fluid leakage cases, ect. Twenty-eight cases were followed up for more than 3 months (3 to 40 months), 1 case of chordoma had tumor progression; the nerve function was restored in 5 cases, among the 12 cases with postoperatively new occurred or deteriorated cranial nerve paralysis. CONCLUSIONS: The pretemporal transcavernous approach can be used to resect tumors limited in cavernous sinus or tumors simultaneously involving the cavernous sinus and its vicinity areas, it can be individually tailored based on the extent and exposure of the tumor. This approach can improve the surgical results in terms of high tumor resection rate, less complication, is an ideal approach for cavernous sinus tumor resection.


Assuntos
Adenoma/cirurgia , Seio Cavernoso/patologia , Cordoma/cirurgia , Hemangioma/cirurgia , Meningioma/cirurgia , Neoplasias Hipofisárias/cirurgia , Adolescente , Adulto , Idoso , Seio Cavernoso/cirurgia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Período Pós-Operatório , Radiocirurgia , Estudos Retrospectivos , Adulto Jovem
13.
Cancer Med ; 5(7): 1510-8, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27165693

RESUMO

The conventional histologic grading of colorectal cancer (CRC) is less suited for resected rectal cancer following neoadjuvant chemoradiation. Enumeration of poorly differentiated clusters (PDC) is a recently proposed histologic grading scheme. We aimed to apply PDC grading to treated rectal cancer and to test the prognostic significance of this novel approach. Archived hematoxylin and eosin slides of 72 rectal adenocarcinomas resected following neoadjuvant treatment were retrieved. PDC, tumor budding, and tumor regression were assessed. The parameters were correlated with clinicopathological features and survival. PDC was strongly associated with tumor budding, perineural invasion (PNI), metastasis, and low degree of tumor regression. Tumor budding was significantly associated with lymphovascular invasion and PNI, and metastasis. Tumors with a lower degree of regression were more likely to show high pathologic T stage and advanced clinical stage. Local recurrence was associated with poor survival. PDC did not correlate with overall survival. PDC grading is applicable to resected rectal cancer status post neoadjuvant treatment and correlates with established histopathological prognosticators. PDC and tumor budding may represent a histologic spectrum reflective of the same biological significance. Validation and incorporation of these simple histologic grading schemes may strengthen the prognostic power of the histologic parameters that influence the oncologic outcome in treated rectal cancer. Further study to evaluate the significance of PDC as an oncologic prognosticator is warranted.


Assuntos
Neoplasias Retais/diagnóstico , Neoplasias Retais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Tomada de Decisão Clínica , Gerenciamento Clínico , Progressão da Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/cirurgia
14.
J Cancer Res Ther ; 12(1): 198-203, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27072237

RESUMO

CONTEXT: It has been verified that dendritic cell (DC) vaccination can improve the prognosis of malignant glioma. However, recent evidence suggests the problems with DC vaccines lies, at least in part, with the cancers ability to induce an immunosupressive response that suppresses any vaccine-mediated active immunity. Our previous studies indicate that subcutaneous vaccine can restrain the cancer cells implanted in the brain, but the effect is limited on vascularized tumor in the brain. Furthermore, vascular endothelial growth factor (VEGF) and vascular cell adhesion molecule (VCAM) play an important role in immunoevasion. AIMS: To identify the effects of DC vaccination on antiangiogenesis induced by endostatin in rat glioma. MATERIALS AND METHODS: Rat basal ganglia glioma model was constructed and authenticated. The concentration of immunoglobulin G (IgG) was detected using rat IgG enzyme-linked immunosorbent assay (ELISA) kit. CD8+ T cell infiltration was measured by immunofluorescence. The expression of VEGF, VCAM, and intercellular adhesion molecule 1 (ICAM-1) tested by real-time reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. The expression of VEGF and apoptosis in rat glioma tissues is tested by immunohistochemical staining. STATISTICAL ANALYSIS USED: Two group comparisons were analyzed by a two-tailed Student's t test. Multiple group comparisons were analyzed by one-way analysis of variance (ANOVA). P values less than 0.05 were considered statistically significant. RESULTS: The combination of DC vaccination and antiangionesis inhibited the rats with malignant glioma by stimulating immune response, supressing the expression of angiogenesis-related proteins VEGF, VCAM, and ICAM-1. In addition, the combination therapy inhibited glioma stem-cell-like cells. CONCLUSIONS: DC vaccination enhances antiangiogenesis induced by endostatin in rat glioma.


Assuntos
Endostatinas/administração & dosagem , Glioma/tratamento farmacológico , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão de Célula Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Animais , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Células Dendríticas/transplante , Glioma/genética , Glioma/imunologia , Glioma/patologia , Humanos , Imunoterapia , Molécula 1 de Adesão Intercelular/imunologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/imunologia , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/imunologia , Neovascularização Patológica/patologia , Ratos , Linfócitos T/imunologia , Molécula 1 de Adesão de Célula Vascular/imunologia , Fator A de Crescimento do Endotélio Vascular/imunologia
15.
Cell Physiol Biochem ; 35(2): 419-32, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25613036

RESUMO

BACKGROUND: Metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors that mediate neuronal excitability and synaptic plasticity in the central nervous system, and emerging evidence suggests a role of mGluRs in the biology of cancer. Previous studies showed that mGluR1 was a potential therapeutic target for the treatment of breast cancer and melanoma, but its role in human glioma has not been determined. METHODS: In the present study, we investigated the effects of mGluR1 inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA) or selective antagonists Riluzole and BAY36-7620. The anti-cancer effects of mGluR1 inhibition were measured by cell viability, lactate dehydrogenase (LDH) release, TUNEL staining, cell cycle assay, cell invasion and migration assays in vitro, and also examined in a U87 xenograft model in vivo. RESULTS: Inhibition of mGluR1 significantly decreased the cell viability but increased the LDH release in a dose-dependent fashion in U87 cells. These effects were accompanied with the induction of caspase-dependent apoptosis and G0/G1 cell cycle arrest. In addition, the results of Matrigel invasion and cell tracking assays showed that inhibition of mGluR1 apparently attenuated cell invasion and migration in U87 cells. All these anti-cancer effects were ablated by the mGluR1 agonist L-quisqualic acid. The results of western blot analysis showed that mGluR1 inhibition overtly decreased the phosphorylation of PI3K, Akt, mTOR and P70S6K, indicating the mitigated activation of PI3K/Akt/mTOR pathway. Moreover, the anti-tumor activity of mGluR1 inhibition in vivo was also demonstrated in a U87 xenograft glioma model in athymic nude mice. CONCLUSION: The remarkable efficiency of mGluR1 inhibition to induce cell death in U87 cells may find therapeutic application for the treatment of glioma patients.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Neoplasias Encefálicas/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Glioma/metabolismo , Humanos , Camundongos , Camundongos Nus , Terapia de Alvo Molecular , Naftalenos/administração & dosagem , Naftalenos/farmacologia , Ácido Quisquálico/farmacologia , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacologia , Receptores de Glutamato Metabotrópico/metabolismo , Riluzol/administração & dosagem , Riluzol/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Zhonghua Wai Ke Za Zhi ; 52(7): 508-13, 2014 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-25262607

RESUMO

OBJECTIVE: To identify factors that predictive of quality of life after microsurgical removal of petroclival meningiomas. METHODS: A consecutive series of 71 cases of petroclival meningiomas received microsurgical removal between July 1991 and April 2010 were analyzed retrospectively. Quality of life was measured using Karnofsky performance scale (KPS). Complete pre-operative, post-operative and follow-up data were obtained from all 71 patients including 18 male and 53 female patients with the mean age of (47 ± 11) years (aging from 15 to 68 years). The duration between onset of symptoms and diagnosis ranged from 1 week to 180 months with the mean duration of (32 ± 30) months. And the tumor size was 15-72 mm with the average of (44 ± 11) mm. Main presentations included headache, unsteady gait, hemiparesis, dysphagia, hoarseness, facial numbness or pain, Bell's palsy, hearing impairment etc. The preoperative KPS was 40-100 with the average of 69 ± 11. The retrosigmoid (-transtentorial) approach was performed in most cases (91.5%). Intergroup χ² test and logistic regression analysis were conducted for prognostic factor characterization. RESULTS: The gross total resection (all were Simpson gradeII) reached in 48 cases (67.6%) and 1 case died postoperatively. The main new neurological dysfunctions were cranial nerve paralysis and hemiplegia with the postoperative KPS of 20-100 with the average of 73 ± 16.Sixty-four cases were followed for 4-132 months with the average of (61 ± 48) months. Seven patients died during follow-up, tumor recurrence and progression were identified in 6 and 8 cases, respectively. The KPS at the last visit ranged from 50 to 100 with the average of 83 ± 13. The extent of tumor resection (OR = 0.280, 95% CI: 0.081-0.967, P = 0.044), preoperative brainstem edema (OR = 0.100, 95% CI: 0.027-0.372, P = 0.001), relationships between tumor and neurovascular structures (OR = 0.288, 95% CI: 0.084-0.985, P = 0.047) and depth of invasion into cavernous sinus (OR = 0.254, 95% CI: 0.061-1.057, P = 0.048) had significant correlations with the prognostic quality of life. CONCLUSIONS: With regard of the choice of surgical approaches, the extent of tumor resection, the protection of neurovascular structures surrounding the tumor and the management of perioperative period, the therapeutic strategies for each patient should be customized to achieve better prognosis.


Assuntos
Neoplasias Meníngeas/cirurgia , Microcirurgia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico , Pessoa de Meia-Idade , Prognóstico , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
J Vis Exp ; (89)2014 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-25046572

RESUMO

It is crucial to identify cytomegalovirus (CMV) infection in the gastrointestinal (GI) tract of immunosuppressed patients, given their greater risk for developing severe infection. Many laboratory methods for the detection of CMV infection have been developed, including serology, viral culture, and molecular methods. Often, these methods reflect systemic involvement with CMV and do not specifically identify local tissue involvement. Therefore, detection of CMV infection in the GI tract is frequently done by traditional histology of biopsy tissue. Hematoxylin and eosin (H&E) staining in conjunction with immunohistochemistry (IHC) have remained the mainstays of examining these biopsies. H&E and IHC sometimes result in atypical (equivocal) staining patterns, making interpretation difficult. It was shown that quantitative polymerase chain reaction (qPCR) for CMV can successfully be performed on formalin-fixed, paraffin-embedded (FFPE) biopsy tissue for very high sensitivity and specificity. The goal of this protocol is to demonstrate how to perform qPCR testing for the detection of CMV in FFPE biopsy tissue in a clinical laboratory setting. This method is likely to be of great benefit for patients in cases of equivocal staining for CMV in GI biopsies.


Assuntos
Citomegalovirus/genética , DNA Viral/análise , Reação em Cadeia da Polimerase/métodos , Animais , Biópsia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/virologia , Formaldeído , Imuno-Histoquímica , Inclusão em Parafina , Fixação de Tecidos
18.
Brain Res ; 1555: 1-9, 2014 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-24508577

RESUMO

Mood stabilizer valproic acid (VPA), a widely used antiepileptic drug that has been demonstrated neuroprotective effect against various insults through multiple signaling pathways. The role of VPA in traumatic brain injury (TBI) remains unclear. In the present study, we investigated the neuroprotective potency of VPA for protection against TBI in adult rats, focusing on studying signaling mediators of two well characterized pro-survival molecules, extracellular signal-regulated protein kinase (ERK) and Akt. We found that treatment of VPA after TBI significantly attenuated brain edema, reduced contusion volume and the rate of neuronal apoptosis. The treatment also partly blocked an increase in capase-3 activity. VPA markedly up-regulated the activity of ERK and Akt expression. Moreover, treatment with either PD98059, an ERK inhibitor and/or LY294002, an Akt inhibitor, attenuated the neuroprotection of VPA against TBI to varying degrees. Taken together, these results demonstrated that treatment with VPA after TBI could be neuroprotective via activation of ERK and Akt signaling pathways.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Córtex Cerebral/enzimologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ácido Valproico/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Lesões Encefálicas/enzimologia , Lesões Encefálicas/patologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
19.
Mol Biol Rep ; 41(4): 2543-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24469715

RESUMO

Several previous studies have evaluated the association between rs1149048 polymorphism in the matrilin-1 gene (MATN1) and the risk of adolescent idiopathic scoliosis (AIS). However the results of those studies were inconsistent. We conducted this meta-analysis to assess whether rs1149048 polymorphism was involved in the risk of AIS and evaluated the associations in different ethnicities. Electronic databases, such as: PubMed, EMBASE, WANFANG databases in any languages up to Dec 2012 were searched to assess the association between rs1149048 polymorphism and AIS. Meta-analysis was performed by STATA 12.0 software to estimate the pooled odds ratio (OR) and the 95 % confidence interval (CI). Finally four papers including five studies which involved 1436 AIS patients and 1,879 controls were identified for this meta-analysis. The results showed that G allele of the rs1149048 was significantly associated with increased AIS risk [OR = 1.13, 95 % CI (1.02-1.25), P = 0.023]. As for genotype (GG vs. GA + AA), homozygous GG genotype was also found to be a risk factor of developing AIS. The subgroup meta-analysis results showed G allele and GG genotype were significantly associated with AIS in Asian group but not in Caucasian group. Neither Egger's test nor Begg's test found evidence of publication bias in current study (P > 0.05). In summary, this meta-analysis found an overall significant association of rs1149048 polymorphism with risk of AIS, especially in Asian population. The relationship between rs1149048 polymorphism and AIS in other ethnic population is needed to be investigated.


Assuntos
Alelos , Predisposição Genética para Doença , Proteínas Matrilinas/genética , Polimorfismo Genético , Escoliose/genética , Fatores Etários , Grupos Étnicos/genética , Estudos de Associação Genética , Genótipo , Humanos , Razão de Chances , Viés de Publicação , Risco
20.
Med Oncol ; 31(3): 859, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24477653

RESUMO

miR-200b is a tumor suppressor in multiple tumors including gastric cancer, breast cancer, ovarian cancer and glioma. In this study, we detected the expression of miR-200b and analyzed its correlation with clinicopathological parameters in glioma tissues. miR-200b was downregulated in glioma tissues. And its downexpression was correlated with poor prognosis in gliomas. Members of RAB family, RAB21, RAB23, RAB18 and RAB3B were predicted to be novel targets of miR-200b. The direct suppression of RAB21, RAB23, RAB18 and RAB3B expressions by miR-200b was revealed by luciferase reporter assay, quantitative RT-PCR analysis and Western blot. Furthermore, the overall survival of patients with different expression of RABs was analyzed. The expression of RAB21, RAB23, RAB18 and RAB3B was related to the prognosis and histopathology of glioma. The patients who had the upregulation of all the four RABs had the worst outcome; those who had the downregulation of all RABs had the best outcome (p<0.001). miR-200b was a potential biomarker for glioma prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Glioma/genética , MicroRNAs/genética , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab3 de Ligação ao GTP/metabolismo , Biomarcadores Tumorais/genética , Western Blotting , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Feminino , Seguimentos , Glioma/mortalidade , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Proteínas rab de Ligação ao GTP/genética , Proteínas rab3 de Ligação ao GTP/genética
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