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1.
J Biol Chem ; 294(25): 10006-10017, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31101655

RESUMO

Nucleus accumbens-associated protein-1 (NAC1) is a transcriptional repressor encoded by the NACC1 gene, which is amplified and overexpressed in various human cancers and plays critical roles in tumor development, progression, and drug resistance. NAC1 has therefore been explored as a potential therapeutic target for managing malignant tumors. However, effective approaches for effective targeting of this nuclear protein remain elusive. In this study, we identified a core unit consisting of Met7 and Leu90 in NAC1's N-terminal domain (amino acids 1-130), which is critical for its homodimerization and stability. Furthermore, using a combination of computational analysis of the NAC1 dimerization interface and high-throughput screening (HTS) for small molecules that inhibit NAC1 homodimerization, we identified a compound (NIC3) that selectively binds to the conserved Leu-90 of NAC1 and prevents its homodimerization, leading to proteasomal NAC1 degradation. Moreover, we demonstrate that NIC3-mediated down-regulation of NAC1 protein sensitizes drug-resistant tumor cells to conventional chemotherapy and enhances the antimetastatic effect of the antiangiogenic agent bevacizumab both in vitro and in vivo These results suggest that small-molecule inhibitors of NAC1 homodimerization may effectively sensitize cancer cells to some anticancer agents and that NAC1 homodimerization could be further explored as a potential therapeutic target in the development of antineoplastic agents.

2.
Cancer Biol Ther ; 20(3): 240-246, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30252567

RESUMO

More than 90% of thyroid cancer belongs to the papillary and follicular thyroid carcinomas based on pathological subtypes. Papillary and follicular thyroid carcinoma are generally associated with a good prognosis. In contrast, other pathological subtypes such as poorly-differentiated and anaplastic thyroid carcinoma (PDTC and ATC) have a poor clinical outcome with a short life expectancy. To identify the genetic variations and biomarkers that may potentially distinguish the aggressive form of thyroid cancer, we performed a retrospective analysis of the formalin-fixed paraffin-embedded tumor samples from 50 patients who mainly displayed aggressive thyroid cancer using next-generation sequencing of 416 solid tumor-related genes. We adopted extensive bioinformatic analysis to vigorously remove germline single-nucleotide polymorphism and systematic sequencing errors, and report here that mutation in DNMT3A gene was significantly enriched in patients with PDTC or ATC.

3.
Exp Ther Med ; 16(6): 4616-4622, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30542412

RESUMO

Acute lung injury (ALI) is a frequent, but severe complication following sepsis in patients with critical illness. The present study aimed to investigate the potential role of microRNA-21 (miR-21) in the regulation of inflammation in the ALI induced by lipopolysaccharide (LPS) in vitro and in vivo. The levels of inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß and IL-10, and the level of miR-21 expression were measured in the lungs of LPS-induced ALI rats and NR8383 alveolar macrophages (AMs). To confirm the regulatory effect of miR-21 in the inflammatory reactions of ALI, NR8383 cells were transfected with a mimic of miR-21 or an anti-miR-21 inhibitor, and the subsequent changes of the miR-21 level and the levels of inflammatory cytokines were detected. The underlying molecular mechanism was also investigated. LPS-induced ALI in rats resulted in significant overexpression of pro-inflammatory cytokines, TNF-α, IL-6 and IL-1ß, and miR-21, but reduced the expression of the anti-inflammatory cytokine IL-10. LPS treatment also led to a higher expression level of miR-21 and increased secretion of pro-inflammatory cytokines in NR8383 cells in a time-dependent manner. Manipulation with the miR-21 mimic significantly suppressed the LPS-mediated induction of TNF-α, IL-6 and IL-1ß in NR8383 cells, while that induction was upregulated when miR-21 expression was silenced via transfection with the anti-miR-21 inhibitor. Further mechanism experiments revealed that miR-21 regulates LPS-induced inflammation responses via the Toll-like receptor 4 and nuclear factor-κB (Nf-κB) signaling pathway. miR-21 negatively regulates inflammatory responses in LPS-induced ALI by targeting the NF-κB signaling pathway, providing further insight into the molecular mechanism of ALI progression.

4.
Cancer Lett ; 418: 64-74, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29331413

RESUMO

The roles of microRNA in regulation of various biological processes and in modulation of therapeutic effects have been widely appreciated. In this study, we found a positive correlation between miR-449 b expression and radiation sensitivity in cancer cells and in tumor specimens from patients. We showed that eEF-2 kinase, a negative regulator of global protein synthesis, is a target of miR-449 b. Introducing a miR-449 b mimic into cancer cells led to suppression of eEF-2 kinase expression, leading to increases of protein synthesis and depletion of cellular ATP. Further, we demonstrated that the miR-449 b mimic rendered the cancer cells more sensitive to ionizing radiation both in vitro (cell culture) and in vivo (animal xenograft model). Moreover, the radiation sensitivity conferred by miR-449 b could be blunted by cycloheximide, an inhibitor of protein synthesis, or by direct delivery of ATP liposome, supporting eEF-2 kinase as a mediator of the radio-sensitizing effects of miR-449 b. These results indicate that miR-449 b, which is frequently down-regulated in radio-resistant cancers, may represent a new critical determinant of radio-sensitivity.


Assuntos
Quinase do Fator 2 de Elongação/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias/genética , Neoplasias/radioterapia , Tolerância a Radiação/genética , Regiões 3' não Traduzidas/genética , Células A549 , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Sobrevivência Celular/efeitos da radiação , Quinase do Fator 2 de Elongação/metabolismo , Feminino , Células HeLa , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
ISA Trans ; 72: 256-272, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29173939

RESUMO

This paper concerns wire rope tension control of a double-rope winding hoisting system (DRWHS), which consists of a hoisting system employed to realize a transportation function and an electro-hydraulic servo system utilized to adjust wire rope tensions. A dynamic model of the DRWHS is developed in which parameter uncertainties and external disturbances are considered. A comparison between simulation results using the dynamic model and experimental results using a double-rope winding hoisting experimental system is given in order to demonstrate accuracy of the dynamic model. In order to improve the wire rope tension coordination control performance of the DRWHS, a robust nonlinear adaptive backstepping controller (RNABC) combined with a nonlinear disturbance observer (NDO) is proposed. Main features of the proposed combined controller are: (1) using the RNABC to adjust wire rope tensions with consideration of parameter uncertainties, whose parameters are designed online by adaptive laws derived from Lyapunov stability theory to guarantee the control performance and stability of the closed-loop system; and (2) introducing the NDO to deal with uncertain external disturbances. In order to demonstrate feasibility and effectiveness of the proposed controller, experimental studies have been conducted on the DRWHS controlled by an xPC rapid prototyping system. Experimental results verify that the proposed controller exhibits excellent performance on wire rope tension coordination control compared with a conventional proportional-integral (PI) controller and adaptive backstepping controller.

6.
Front Pharmacol ; 8: 804, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29163184

RESUMO

In order to survive under conditions of low oxygen, cancer cells can undergo a metabolic switch to glycolysis and suppress mitochondrial respiration in order to reduce oxygen consumption and prevent excessive amounts of reactive oxygen species (ROS) production. Nucleus accumbens-1 (NAC1), a nuclear protein of the BTB/POZ gene family, has pivotal roles in cancer development. Here, we identified that NAC1-PDK3 axis as necessary for suppression of mitochondrial function, oxygen consumption, and more harmful ROS generation and protects cancer cells from apoptosis in hypoxia. We show that NAC1 mediates suppression of mitochondrial function in hypoxia through inducing expression of pyruvate dehydrogenase kinase 3 (PDK3) by HIF-1α at the transcriptional level, thereby inactivating pyruvate dehydrogenase and attenuating mitochondrial respiration. Re-expression of PDK3 in NAC1 absent cells rescued cells from hypoxia-induced metabolic stress and restored the activity of glycolysis in a xenograft mouse model, and demonstrated that silencing of NAC1 expression can enhance the antitumor efficacy of elesclomol, a pro-oxidative agent. Our findings reveal a novel mechanism by which NAC1 facilitates oxidative stress resistance during cancer progression, and chemo-resistance in cancer therapy.

7.
BMC Cancer ; 17(1): 652, 2017 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-28923053

RESUMO

BACKGROUND: The increasing incidence and poor outcome associated with malignant pleural effusion (MPE) requires finding an effective treatment for this disease. Inhibitory B7-H4 is expressed in many different human cancers but its role in malignant pleural tissue has yet to be established. METHODS: Here, patients with metastatic pleural adenocarcinoma (MPA) or with early-stage lung adenocarcinoma were clinically and statistically analyzed. Immunohistochemistry and confocal microscopy were used to determinate the expression of B7-H4 in the cancer cells. By using MPE model, we sought to a potential immunotherapy for MPE with anti-B7-H4 mAb. RESULTS: When compared to early-stage lung adenocarcinoma, MPA possessed higher level of nuclei membranous B7-H4 and lower cytoplasmic B7-H4 expression. Also, nuclei membranous B7-H4 expression was found to be positively correlated to Ki-67 expression, and indicated a possible poor prognosis of MPA. In mouse MPE model, intra-pleurally injection of anti-B7-H4 mAb effectively suppressed MPE formation. CONCLUSIONS: Taken together, our data was in support of the significance of B7-H4 expression in MPA, which also suggest it warrants further exploration for potential immunotherapy of MPE.


Assuntos
Adenocarcinoma/metabolismo , Antineoplásicos/farmacologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pleurais/metabolismo , Inibidor 1 da Ativação de Células T com Domínio V-Set/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Animais , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Linhagem Celular Tumoral , Citoplasma/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Transplante de Neoplasias , Membrana Nuclear/metabolismo , Derrame Pleural Maligno , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/secundário , Inibidor 1 da Ativação de Células T com Domínio V-Set/antagonistas & inibidores
8.
Zhonghua Nan Ke Xue ; 23(5): 392-398, 2017 May.
Artigo em Chinês | MEDLINE | ID: mdl-29717827

RESUMO

Objective: To explore the effects of immediate and delayed intracavernous injection of bone marrow mesenchymal stem cells (BM-MSCs) on neurogenic erectile dysfunction (NED) induced by bilateral cavernous nerve injury in Sprague-Dawley (SD) rats. METHODS: BM-MSCs isolated from male SD rats were cultured and identified. Twenty-eight 8-week-old male SD rats were randomly divided into four groups, sham operation, NED model control, BM-MSCs immediate, and BM-MSCs delayed, and NED models were established in the latter three groups by crushing the bilateral cavernous nerves. The rats in the sham operation and model control groups were injected intracavernously with placebo while those in the latter two with BM-MSCs immediately or 2 weeks after modeling. At 12 weeks after operation, the penile function of the rats was assessed according to the penile intracavernous pressure (ICP), mean arterial pressure (MAP), and ICP/MAP ratio obtained from different groups of rats. Then, all the animals were sacrificed and the penile cavernosal tissue collected for histological analysis. RESULTS: At 12 weeks after modeling, both ICP and ICP/MAP were significantly increased in the BM-MSCs immediate and delayed groups as compared with those in the model control (P <0.05), and so were the ratio of smooth muscle to collagen (P <0.05) and the smooth muscle content in the corpus cavernosum (P <0.05), and the number of neurofilament (NF)-positive nerve fibers (P <0.05) and the expression of neuronal nitric oxide synthase (nNOS) in the dorsal nerves of the midshaft penis (P <0.05). CONCLUSIONS: Intracavernous injection of BM-MSCs can improve erectile function in rats with bilateral cavernous nerve injury by elevating the smooth muscle-collagen ratio and smooth muscle content in the corpus cavernosum and thus preventing its fibrosis as well as by increasing the number of NF-positive nerve fibers and expression of nNOS in the penile dorsal nerves.


Assuntos
Disfunção Erétil/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Pênis/inervação , Animais , Modelos Animais de Doenças , Disfunção Erétil/enzimologia , Disfunção Erétil/etiologia , Masculino , Músculo Liso , Óxido Nítrico Sintase Tipo I/metabolismo , Ereção Peniana/fisiologia , Pênis/enzimologia , Nervo Pudendo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
9.
Genet Med ; 19(5): 553-558, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27657680

RESUMO

PURPOSE: To explore the genetic etiology of deafness in a dominant family with late-onset, progressive, nonsyndromic hearing loss. METHODS: Genome-wide linkage analysis was performed for 21 family members. Candidate pathogenic variants were identified by whole-exome sequencing of selected family members and confirmed by Sanger sequencing of all family members. Cochlear expression of Dmxl2 was investigated by reverse-transcription polymerase chain reaction (RT-PCR) and immunostaining of the organ of Corti from mice. RESULTS: The causative gene was mapped to a 9.68-Mb candidate region on chromosome 15q21.2 (maximum logarithm of the odds score = 4.03) that contained no previously described deafness genes. Whole-exome sequencing identified heterozygous c.7250G>A (p.Arg2417His) in DMXL2 as the only candidate pathogenic variant segregating the hearing loss. In mouse cochlea, expression of DMXL2 was restricted to the hair cells and the spiral ganglion neurons. CONCLUSION: Our data indicated that the p.Arg2417His variant in DMXL2 is associated with dominant, nonsyndromic hearing loss and suggested an important role of DMXL2 in inner ear function.Genet Med advance online publication 22 September 2016.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Surdez/genética , Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso/genética , Órgão Espiral/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idade de Início , Animais , China/etnologia , Surdez/metabolismo , Feminino , Estudos de Associação Genética , Ligação Genética , Predisposição Genética para Doença , Humanos , Masculino , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Linhagem , Mapeamento Físico do Cromossomo , Sequenciamento Completo do Exoma
10.
Neurotox Res ; 31(2): 204-217, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27848175

RESUMO

Severe hand-foot-and-mouth disease (HFMD) caused by Enterovirus 71 (EV71) always accompanies with inflammation and neuronal damage in the central nervous system (CNS). During neuronal injuries, cell surface-exposed calreticulin (Ecto-CRT) is an important mediator for primary phagocytosis of viable neurons by microglia. Our data confirmed that brainstem neurons underwent neuronophagia by glia in EV71-induced death cases of HFMD. EV71 capsid proteins VP1, VP2, VP3, or VP4 did not induce apoptosis of brainstem neurons. Interestingly, we found VP1-activated endoplasmic reticulum (ER) stress and autophagy could promote Ecto-CRT upregulation, but ER stress or autophagy alone was not sufficient to induce CRT exposure. Furthermore, we demonstrated that VP1-induced autophagy activation was mediated by ER stress. Meaningfully, we found dexamethasone treatment could attenuate Ecto-CRT upregulation by alleviating VP1-induced ER stress. Altogether, these findings identify VP1-promoted Ecto-CRT upregulation as a novel mechanism of EV71-induced neuronal cell damage and highlight the potential of the use of glucocorticoids to treat severe HFMD patients with CNS complications.


Assuntos
Calreticulina/metabolismo , Proteínas do Capsídeo/toxicidade , Dexametasona/farmacologia , Estresse do Retículo Endoplasmático/fisiologia , Neurônios/fisiologia , Fagocitose/fisiologia , Proteínas Estruturais Virais/toxicidade , Animais , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/fisiopatologia , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Humanos , Masculino , Fagocitose/efeitos dos fármacos , Ratos , Regulação para Cima
11.
Oncotarget ; 7(36): 58563-58568, 2016 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-27438152

RESUMO

PURPOSE: Although the pathogenicity of B7-H4 in cancer is well established, its role in pulmonary adenocarcinoma, especially lesions presenting as solitary pulmonary nodules (SPNs), remains unclear. METHODS: 40 cases of pulmonary adenocarcinoma presenting with SPN were enrolled during year 2012-2015. The B7-H4 expression and its subcellular distribution in pulmonary adenocarcinoma presenting with SPN were analyzed by immunohistochemistry, further its correlation with Ki-67 expression and CT feature. In vitro, the B7-H4 expression in the cytoplasmic and nucleus fractions of lung cancer cell lines was determinate by western blotting. RESULTS: Immunostaining revealed B7-H4 in the cytoplasm of cells from all 40 SPN samples studied. No surface localization of B7-H4 was detected, but in 18 samples the nuclear membranes were B7-H4-positive. Moreover, patients with more poorly differentiated and invasive adenocarcinomas showed greater localization of B7-H4 to the nuclear membrane. The percentage of lesions with ground-glass opacity was significantly greater among samples negative for nuclear membrane B7-H4. Most importantly, there was a statistically significant relationships between the Ki-67 index and B7-H4 positivity of the nuclear membrane. This suggests tumors exhibiting higher nuclear membrane B7-H4 have greater proliferative potential. Western blotting confirmed both cytoplasmic and nuclear B7-H4 localization in lung adenocarcinoma cell lines. CONCLUSIONS: Taken together, our study provides a new insight into the tumorigenicity of B7-H4 in lung adenocarcinoma. We suggest that in pulmonary adenocarcinoma presenting with SPN, nuclear membrane localization of B7-H4 within the tumor cells is associated with increased malignancy.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias Pulmonares/metabolismo , Nódulo Pulmonar Solitário/metabolismo , Inibidor 1 da Ativação de Células T com Domínio V-Set/metabolismo , Células A549 , Adenocarcinoma/diagnóstico , Adenocarcinoma de Pulmão , Adulto , Idoso , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Nódulo Pulmonar Solitário/diagnóstico , Procedimentos Cirúrgicos Torácicos , Toracotomia , Tomografia Computadorizada por Raios X
12.
Br J Biomed Sci ; 73(1): 32-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27182675

RESUMO

PURPOSE: This study was designed to determine whether proliferation antigen Ki-67 and/or a computed tomography (CT) value could be used to evaluate the clinical-pathological features of peripheral lung adenocarcinoma. MATERIALS AND METHODS: A total of 116 eligible lung cancer patients were enrolled. Nodule size, lymph node metastasis, differentiation, Ki-67 expression and CT findings were assessed. The relationship between clinic parameters and the CT feature was analysed statistically. RESULTS: The percentage of lesions that had ground-glass opacity or localised air bronchogram was significantly greater in low CT value group (<30, p < 0.05). No significant association was observed between CT value and size in the subgroup with CT value > 0 (p = 0.66). As a proliferative marker of lung cancer, Ki-67 was present in a total of 115 (99.9%) of the 116 evaluable primary lung cancers. There was a statistically significant correlation between the Ki-67 index and CT value (p < 0.05). Compared to CT value, Ki-67 index possessed higher sensitivity to predict the differentiation and lymph node metastasis of peripheral lung adenocarcinoma, adding of CT value would enhance its specificity. CONCLUSION: Combination of Ki-67 expression and CT value determination was useful for the classification of differentiation and metastatic or proliferative potential of peripheral lung adenocarcinoma.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/análise , Proliferação de Células , Imuno-Histoquímica , Antígeno Ki-67/análise , Neoplasias Pulmonares/diagnóstico , Tomografia Computadorizada por Raios X , Adenocarcinoma/química , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Diferenciação Celular , Feminino , Humanos , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Resultado do Tratamento , Carga Tumoral
13.
Eur Arch Otorhinolaryngol ; 273(5): 1115-21, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25997899

RESUMO

The aim of the study was to describe the refinements to the classic enlarged translabyrinthine approach (ETLA) by modifying the bony dissection range of temporal bone and to analyze the main outcomes achieved in a series of vestibular schwannoma (VS) cases submitted to microsurgery by ETLA. This was a retrospective study of 382 patients who underwent VS surgical removal via ETLA between January 2001 and December 2012. Among those cases, 332 were via classic ETLA, while 28 cases were via ETLA with blind sac technique and middle ear eradication and 22 via transotic approach. Total tumor removal was achieved in 368 cases, whereas near total removal in 11 patients and subtotal in 3 patients. In cases of large VS (>3 cm) via classic ETLA, good short-term and long-term facial nerve function (HB I-II) was gained in 27.8 % (32/115) and 42.6 % (49/115) cases, respectively, meanwhile in VS operated via blind sac technique, good short-term (p = 0.048) and long-term (p = 0.044) facial nerve function was reached in 44.0 % (22/50) and 60.0 % (30/50) cases, respectively. Postoperative facial nerve function was proved to be better in modified ETLA group. CSF leakage occurred in 16 (4.2 %) patients via classic ETLA. In 115 cases of large VS (>3 cm), postoperative CSF leakage occurred in 10 (8.7 %) patients. Whereas in 50 cases via blind sac technique, none developed CSF leakage (p = 0.03). The incidence of CSF leakage was lower in modified ETLA group. Our refinements to classic ETLA by changing the temporal bone resection range provide a wide surgical field, well prevention of CSF leakage and preservation of facial nerve function in large VS.


Assuntos
Vazamento de Líquido Cefalorraquidiano/prevenção & controle , Tomada de Decisão Clínica , Dissecação/efeitos adversos , Microcirurgia/efeitos adversos , Neuroma Acústico/cirurgia , Osso Temporal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vazamento de Líquido Cefalorraquidiano/diagnóstico , Vazamento de Líquido Cefalorraquidiano/epidemiologia , Dissecação/métodos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/patologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Osso Temporal/patologia , Adulto Jovem
14.
J Biomed Mater Res A ; 104(1): 9-16, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26148477

RESUMO

The goal of this study was to investigate the tissue performance of bladder following stretched electrospun silk fibroin matrix (SESFM) implantation compared with bladder acellular matrix (BAM). We compared SESFM with BAM based on porosity and pore size. Scaffolds were separately transplanted into opposite walls of the bladder of 30 rabbits after stripping the bladder mucosa and smooth muscle (1.5 × 2.0 cm(2)). Gross anatomical observation, histological analysis and muscle contractility studies were performed at 2, 4, and 8 weeks post-op. SESFM has higher porosity and larger pore size compared with BAM (p < 0.05). At 2 weeks, the presence of vesical calculus was evident in 7/10 rabbits. Histological analysis showed that SESFM and BAM promoted similar degree of urothelium regeneration (p > 0.05). However, SESFM promoted a higher degree of smooth muscle and vessel regeneration compared to BAM (p < 0.05). In addition, muscle strips supported by SESFM displayed higher contractile responses to carbachol, KCl, and phenylephrine compared with BAM. At 8 weeks, both matrices elicited similar mild acute and chronic inflammatory reactions. Our results demonstrated that SESFM has greater ability to promote bladder tissue regeneration with structural and functional properties compared to BAM, and with similar biocompatibility.


Assuntos
Matriz Extracelular/metabolismo , Fibroínas/farmacologia , Implantação de Prótese , Engenharia Tecidual/métodos , Bexiga Urinária/fisiologia , Animais , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/ultraestrutura , Imuno-Histoquímica , Modelos Animais , Contração Muscular/efeitos dos fármacos , Porosidade , Coelhos , Sus scrofa , Bexiga Urinária/efeitos dos fármacos
15.
J Neurosurg ; 124(3): 639-46, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26406793

RESUMO

OBJECTIVE: Cavernous hemangioma of the internal auditory canal (IAC) is an extremely rare type of tumor, and only 50 cases have been reported in the literature prior to this study. The aim in this study was to describe the symptomatology, radiological features, and surgical outcomes for patients with cavernous hemangioma of the IAC and to discuss the diagnostic criteria and treatment strategy for the disease. METHODS: The study included 6 patients with cavernous hemangioma of the IAC. All patients presented with sensorineural hearing loss and tinnitus, and 2 also suffered from vertigo. Five patients reported a history of facial symptoms with hemispasm or palsy: 3 had progressive facial weakness, 1 had a hemispasm, and 1 had a history of recovery from sudden facial paresis. All patients underwent CT and MRI to rule out intracanalicular vestibular schwannomas and facial nerve neuromas. Five patients had their tumors surgically removed, while 1 patient, who did not have facial problems, was followed up with a wait-and-scan approach. RESULTS: All patients had a presurgical diagnosis of cavernous hemangioma of the IAC, which was confirmed pathologically in the 5 patients who underwent surgical removal of the tumor. The translabyrinthine approach was used to remove the tumor in 4 patients, while the middle cranial fossa approach was used in the 1 patient who still had functional hearing. Tumors adhered to cranial nerves VII and/or VIII and were difficult to dissect from nerve sheaths during surgeries. Complete hearing loss occurred in all 5 patients. In 3 patients, the facial nerve could not be separated from the tumor, and primary end-to-end anastomosis was performed. Intact facial nerve preservation was achieved in 2 patients. Patients were followed up for at least 1 year after treatment, and MRI showed no evidence of tumor regrowth. All patients experienced some level of recovery in facial nerve function. CONCLUSIONS: Cavernous hemangioma of the IAC can be diagnosed preoperatively through analysis of clinical features and neuroimaging. Early surgical intervention may preserve the functional integrity of the facial nerve and provide a better outcome after nerve reconstruction. However, preservation of functional hearing may not be achieved, even with the retrosigmoid or middle cranial fossa approaches. The translabyrinthine approach seems to be the most appropriate approach overall, as the facial nerve can be easily located and reconstructed.


Assuntos
Meato Acústico Externo , Neoplasias da Orelha/diagnóstico , Neoplasias da Orelha/terapia , Hemangioma Cavernoso/diagnóstico , Hemangioma Cavernoso/terapia , Adulto , Estudos de Coortes , Neoplasias da Orelha/patologia , Paralisia Facial/etiologia , Feminino , Perda Auditiva Neurossensorial/etiologia , Hemangioma Cavernoso/patologia , Humanos , Masculino , Zumbido/etiologia , Adulto Jovem
16.
Zhonghua Nan Ke Xue ; 22(9): 771-776, 2016 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-29071871

RESUMO

Objective: To explore the expression of I-5α-reductase (SRD5A1)and its prognostic role in prostate cancer . METHODS: Data about SRD5A1 were retrieved from the ONCOMINE database and the role of SRD5A1 in prostate cancer was analyzed. RESULTS: Totally, 992 studies of different types relevant to the expression of SRD5A1 were identified in the ONCOMINE database. The SRD5A1 expression was statistically significant in 239 of the studies, overexpressed in 157 (11 in prostate cancer) and underexpressed in the other 82 (3 in prostate cancer). Eighteen of the studies, with 1 068 samples, addressed the expression of SRD5A1 in prostate cancer and normal tissues, which was significantly higher in the former than in the latter tissue (P<0.05). In 3 of the studies, the SRD5A1 expression was high in primary prostate cancer and increased with its metastasis (P<0.0 5). Two of the studies with prognostic data showed a higher rate of postoperative biochemical recurrence and a higher total mortality rate in the patients with a high than in those with a low expression of SRD5A1 (P<0.05). CONCLUSIONS: SRD5A1 is highly expressed in prostate cancer, especially in metastatic and castration-resistant prostate cancer and its expression is associated with the prognosis of prostate cancer, which may be an important target of medication for prostate cancer.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Mineração de Dados , Neoplasias da Próstata/enzimologia , Humanos , Masculino , Recidiva Local de Neoplasia , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Neoplasias de Próstata Resistentes à Castração/enzimologia
17.
Zhonghua Nan Ke Xue ; 22(12): 1083-1087, 2016 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29282912

RESUMO

Objective: To explore the expression of long noncoding RNA (lncRNA) LINC01358 in prostate cancer (PCa) and its effect on the proliferation and migration of PCa cells. METHODS: The lncRNA array was used to screen differentially expressed lncRNAs in PCa and the corresponding carcinoma-adjacent normal tissues from 3 patients. The expressions of LINC01358 in the primary PCa, metastatic PCa, and carcinoma-adjacent tissues were compared using the PCa dataset of the Memorial Sloan Kettering Cancer Center (MSKCC). The data obtained were validated by determining the expression of LINC01358 in the PCa and carcinoma-adjacent tissues of another 10 patients by quantitative real time PCR (qRT-PCR). The effects of lncRNA LINC01358 on the proliferation of DU145 cells and migration of PCa cells were detected by MTT and Transwell assay, respectively. RESULTS: Totally, 79 differentially expressed lncRNAs in the lncRNA array, 36 highly and the other 43 lowly expressed in the PCa tissue. LINC01358 was up-regulated in the cancerous tissue. According to the MSKCC data, the LINC01358 expression was markedly higher in metastatic PCa (5.81±0.19, n = 19) and primary PCa (5.47±0.04, n = 131) than in the PCa-adjacent tissue (5.15±0.07, n = 29) and significantly correlated with postoperative biochemical relapse of the malignancy (P<0.05). qRT-PCR indicated a remarkably higher expression of LINC01358 in the PCa than in the carcinoma-adjacent tissue (6.02±1.12 vs 3.21±0.21, P<0.05). Transfection of the DU145 cells with siRNA significantly decreased the level of LINC01358 and inhibited the proliferation and migration of the PCa cells. CONCLUSIONS: LINC01358 is highly expressed in the PCa tissue and knockdown of LINC01358 may inhibit the proliferation and migration of PCa cells. LncRNA LINC01358 may be involved in the development and progression of PCa and become an index for the early diagnosis as well as a new target for the gene therapy of the malignancy.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias da Próstata/metabolismo , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Neoplasias da Próstata/patologia , RNA Interferente Pequeno , Transfecção , Regulação para Cima
18.
Zhonghua Nan Ke Xue ; 21(10): 904-7, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26665679

RESUMO

OBJECTIVE: To compare the outcomes and complications of 3D versus 2D laparoscopic radical prostatectomy ( LRP) in the treatment of prostate cancer. METHODS: We retrospectively reviewed 18 cases of prostate cancer treated by 3D LRP and another 32 by 2D LRP. We compared the general data, intraoperative blood loss, postoperative drainage time and hospital stay, Gleason scores, and incidence of complications between the two groups of patients. RESULTS: All the operations were successful and none was transferred to open surgery. The two groups of patients were similar in terms of age, body mass index, Gleason scores, and clinical stages. However, compared with the 2D LRP group, the 3D LRP group showed significantly shorter operation time ([180.2 ± 69.1] vs [118.3 ± 55.1] min, P < 0.01), less blood loss ([236.5 ± 60.6] vs [89.1 ± 35.2] ml, P < 0.01), less postoperative drainage time ([7.1 ± 1.1] vs [5.3 ± 2.1] d, P < 0.01), shorter postoperative hospital stay ([20.2 ± 5.5] vs [14.4 ± 7.2] d, P < 0.01), and lower incidence of perioperative complications (3.1% vs 0, P < 0.01). The incisal margin was pathologically negative in both groups and urinary incontinence was found in neither at 6 months after surgery (P > 0.05). CONCLUSION: 3D LRP, with its advantages of shorter operative time, faster recovery, and better outcomes than 2D LRP in the treatment of prostate cancer, deserves general application in lower-level hospitals.


Assuntos
Perda Sanguínea Cirúrgica , Laparoscopia/métodos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Índice de Massa Corporal , Drenagem , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Masculino , Gradação de Tumores , Duração da Cirurgia , Prostatectomia/efeitos adversos , Neoplasias da Próstata/patologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Incontinência Urinária/etiologia
19.
J Org Chem ; 80(22): 11521-8, 2015 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-26474033

RESUMO

A formal thio [3+2] cyclization catalyzed by Takemoto's organocatalyst has been reported for the construction of optically active spiroannulated dihydrothiophenes in high yields with excellent regio-, chemo-, diastereo-, and enantioselectivities.

20.
Photomed Laser Surg ; 33(10): 517-23, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26397029

RESUMO

BACKGROUND AND OBJECTIVE: Until now, various laser types have been used in the treatment of bladder cancer. The purpose of this study is to evaluate the feasibility and effectiveness of 2 µm continuous-wave (CW) thulium laser in treating primary non-muscle-invasive bladder cancer (NMIBC). METHODS: A comparative (randomized prospective) interventional study was conducted in our center. A total of 400 patients with Ta or T1 bladder cancer were enrolled and randomized to transurethral resection of bladder tumor (TURBT) or laser vaporesection (LVRBT). Patients in the TURBT group received standard transurethral resection with a bipolar electrocautery system, while those in the LVRBT group received transurethral vaporesction with a 2 µm CW thulium laser. All patients received intravesical irrigation with sterile water for at least 12 h immediately after the procedure. The end-points of this study were tumor recurrence and/or progression, or the completion of 36 months of follow-up (10 cystoscopies) with no recurrence. RESULTS: A total of 292 patients were included in our analysis, of whom 143 received TURBT and 149 received LVRBT. During 36 months of follow-up, 129 cases (44.2%) had recurrence: 61 (42.7%) in the TURBT group and 68 (45.6%) in the LVRBT group (p = 0.608). Tumor progression was found in 19 patients (6.5%): 11 in the TURBT (7.7%) and 8 (5.4%) in the LVRBT group (p = 0.421). Median tumor-free survival was 25.2 months (25.46 in the TURBT group vs. 24.9 in the LVRBT group, p = 0.729). Overall recurrence rate was 14.7%, 42.1%, and 62.5% in the low, intermediate low, and intermediate high risk subgroups, respectively. Operation time was significantly lower in the TURBT than in the LVRBT group (28.43 vs. 31.5 min, p = 0.044). CONCLUSIONS: Use of a 2 µm CW thulium laser is feasible and effective in treating primary NMIBC. With a cystoscopic biopsy of the bladder muscle, 2 µm CW thulium laser could retrieve sufficient diagnostic and prognostic specimens.


Assuntos
Terapia a Laser/métodos , Terapia a Laser/estatística & dados numéricos , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/terapia , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Túlio
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