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1.
Exp Cell Res ; 389(2): 111855, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31978385

RESUMO

Takeda-G-protein-receptor-5 (TGR5) is a G-protein-coupled receptor (GPCR) activated by bile acids, and mortalin is a multipotent chaperone of the HSP70 family. In the present study, TGR5 was detected by immunohistochemistry (IHC) in extrahepatic cholangiocarcinoma (ECC) specimens, and TGR5 expression in ECC tissues and adjacent tissues was compared. In vitro TGR5 was overexpressed and knocked down in human intrahepatic cholangiocarcinoma (ICC) cell line RBE and human extrahepatic cholangiocarcinoma (ECC) cell line QBC-939 to observe its effects on the biological behavior of cholangiocarcinoma (CC) cells, including proliferation, apoptosis and migration. In vivo xenograft model was constructed to explore the role of TGR5 in CC growth. Proteins that interacted with TGR5 were screened using an immunoprecipitation spectrometry approach, and the identified protein was down-regulated to investigate its contribution to CC growth. The present study demonstrated that TGR5 is highly expressed in CC tissues, and strong TGR5 expression may indicate high malignancy in CC. Furthermore, TGR5 promotes CC cell proliferation, migration, and apoptosis resistance. TGR5 boosts CC growth in vivo. In addition, TGR5 combines with mortalin and regulates mortalin expression in the CC cell line. Mortalin participates in the TGR5-induced increase in CC cell proliferation. In conclusion, TGR5 is of clinical significance based on its implications for the degree of malignancy in patients with CC. Mortalin may be a downstream component regulated by TGR5, and TGR5 promotes cholangiocarcinoma at least partially by interacting with mortalin and upregulating its expression. Both TGR5 and mortalin are positive regulators, and may serve as potential therapeutic targets for CC.

2.
Oncol Lett ; 18(3): 2704-2711, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31402956

RESUMO

The effects of the immediate early response 5 (IER5) gene on the sensitivity of HeLa cells to radiation remain unclear. In the present study, stably transfected HeLa cells resulting in the knockdown or overexpression of IER5 were investigated. In addition, xenografts of normal, IER5-silenced and -overexpressed HeLa cells were injected into nude mice and examined. The results demonstrated that the radiosensitivity of the IER5-overexpressed HeLa cells was significantly increased compared with that of the normal and IER5-silenced cells. The upregulation of IER5 effectively decreased cell proliferation and IER5 silencing promoted cell proliferation compared with that in the normal HeLa cells. Following irradiation of the cells with IER5 knockdown, cell cycle was arrested at the G2/M phase and an increase in the proportion of S phase cells was observed. By contrast, the overexpression of IER5 led to an increase in the proportion of G1 phase cells. Furthermore, the upregulation of IER5 inhibited tumor growth in vivo. The present findings demonstrate that the IER5 gene affects the radiosensitivity of HeLa cells and serves an important role in cell proliferation, suggesting that this gene may be a potential radiotherapeutic target in cervical cancer.

3.
Oncol Rep ; 42(1): 263-272, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115555

RESUMO

Piwi­interacting RNAs (piRNAs), a novel class of non­coding RNAs, are enriched in germ cells and implicated in spermatogenesis. Emerging evidence demonstrated deregulated expression of piRNAs in numerous tumor types. However, changes in piRNA expression profiles in colorectal cancer (CRC) have not yet been investigated. In the present study, small RNA sequencing was used to evaluate the differences in piRNA expression profiles between CRC and adjacent non­tumor tissues, as well as to screen for differentially expressed piRNAs. The present results demonstrated that the percentage of unique piRNA reads had no notable difference between the paired CRC and adjacent non­tumor samples (0.12% vs. 0.13%); however, the counts of total piRNA reads in CRC samples were increased, compared with those in adjacent non­tumor samples (0.15% vs. 0.07%). Differential expression analysis identified 33 upregulated piRNAs and 2 downregulated piRNAs in CRC samples, among which piR­18849, piR­19521 and piR­17724 were the top three upregulated piRNAs. Reverse transcription­quantitative polymerase chain reaction further confirmed that the expression levels of piR­18849, piR­19521 and piR­17724 were increased in 80 CRC tissues, compared with paired adjacent non­tumor tissues. Furthermore, the high expression of piR­18849 and piR­19521 was associated with a poor degree of differentiation. The increased expression of piR­18849 was also associated with high lymph node metastasis. However, no associations were determined between piR­17724 expression and clinicopathological characteristics of patients. In summary, the present study is the first to provide an overview of the changes in piRNA expression patterns in CRC, shedding new light on the regulatory roles of piRNAs in colorectal carcinogenesis. piR­18849 and piR­19521 may be prognostic biomarkers for patients with CRC.


Assuntos
Neoplasias Colorretais/genética , Perfilação da Expressão Gênica/métodos , RNA Interferente Pequeno/genética , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sequência de RNA/métodos
4.
Onco Targets Ther ; 12: 2661-2675, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31040704

RESUMO

Purpose: Gastric cancer (GC) patients display aberrant miRNA expression and defective dendritic cell function. However, the role of cancer cell-derived oncomiR in GC detection and dendritic cell (DC) maturation remains largely elusive. Methods: Candidate miRNAs were selected by deep sequencing (8 GC plasma samples vs 8 control plasma samples; 8 GC tissues vs 8 adjacent normal gastric tissues) and confirmed by PCR with 164 plasma samples and 72 formalin-fixed paraffin-embedded GC tissue samples. Their diagnostic performance was evaluated by receiver operating characteristic curve. Cy3 fluorescence signals in DCs, exposed to conditioned medium obtained from BGC-823 cells pre-transfected with Cy3-miR-17-5p, were determined by flow cytometry and visualized by confocal microscopy. Functional and phenotypical alterations of DCs were assayed when DCs were transfected with miR-17-5p in vitro. Results: Deep sequencing and RT-PCR confirmed that five shared miRNAs were upregulated in plasma and tissue samples of GC patients. Cell-free miR-17-5p was superior to others in GC detection with an area under the curve of 0.82, and correlated with lymphatic metastasis and poor overall survival. GC cell-shuttled miR-17-5p can be delivered to immature DCs, and they significantly inhibited LPS-stimulated phenotypic maturation by diminishing the expression of maturation markers (MHC II, CD80 and CD86 molecules). In line with those alterations in the phenotypic markers, functional experiments demonstrated that miR-17-5p triggered an inhibitory effect on DCs endocytic activity and decreased tumor necrosis factor-α and IL-12 secretion, while enhancing IL-10 production. Mixed lymphocyte reaction showed that miR-17-5p inhibited the T cell stimulating effect of DCs and favored regulatory T cells expansion. Conclusion: GC cell-derived miR-17-5p is a potential biomarker for GC detection. Taken up by DCs, miR-17-5p weakened antitumor immune responses via inhibiting the maturation of dendritic cells.

5.
Biomed Res Int ; 2019: 6025726, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30937312

RESUMO

Background: Hyperkalemia is a serious complication in cirrhotic patients. However, the clinical characteristics, risk factors, and its impact on the outcomes in acute-on-chronic liver failure (ACLF) patients remain unclear. Methods: We retrospectively recruited 650 ACLF patients in this study. The risk factors associated with hyperkalemia and its relationship with 90-day mortality were analyzed using multivariable regression models. Results: Among 650 patients with ACLF, 12.2% (79/650) had hyperkalemia during hospitalization. Higher admission serum potassium levels and the presence of acute kidney injury (AKI) were independent risk factors for hyperkalemia. The prevalence rates of hyperkalemia in patients with and without AKI were 23.6% and 4.6%, respectively (P<0.001). Hyperkalemia was a predictor of mortality in AKI and non-AKI patients. The 90-day mortality rates in non-AKI patients with and without hyperkalemia were 44.4% and 24.7%, respectively (P<0.001), and in AKI patients with and without hyperkalemia were 80.3% and 56.6%, respectively (P<0.001). Hepatic encephalopathy (HE), gastrointestinal bleeding, AKI, hyperkalemia, elevated total bilirubin (TBIL) and international normalized ratio (INR) values, and higher Model for End-Stage Liver Disease (MELD) and chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores were independent risk factors for predicting the 90-day mortality in ACLF patients. Conclusions: Hyperkalemia increases the 90-day mortality in ACLF patients; hyperkalemia is associated with AKI. Patients with both AKI and hyperkalemia had the worst outcome.


Assuntos
Insuficiência Hepática Crônica Agudizada/complicações , Hiperpotassemia/complicações , Lesão Renal Aguda/complicações , Insuficiência Hepática Crônica Agudizada/sangue , Insuficiência Hepática Crônica Agudizada/fisiopatologia , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Feminino , Humanos , Hiperpotassemia/sangue , Hiperpotassemia/fisiopatologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Fatores de Risco , Sódio/sangue , Análise de Sobrevida
6.
Exp Mol Med ; 51(1): 6, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30635551

RESUMO

The clearance of activated hepatic stellate cells (HSCs) by apoptosis is critical for the reversibility of hepatic fibrosis. Mitochondrial homeostasis is regulated by mitophagy, which is an efficient way of clearing injured mitochondria that plays an important role in apoptosis. However, the role of mitophagy in apoptosis in HSCs and hepatic fibrosis is still unclear. Here, we show that mitophagy is enhanced in parallel with increased apoptosis in hepatic stellate cells during the reversal of hepatic fibrosis. The inhibition of mitophagy suppressed apoptosis in HSCs and aggravated hepatic fibrosis in mice. In contrast, the activation of mitophagy induced apoptosis in HSCs. Furthermore, we confirmed that BCL-B, which is a member of the BCL-2 family, is a regulator mediating mitophagy-related apoptosis. The knockdown of BCL-B resulted in increased apoptosis and mitophagy in HSCs, while the overexpression of BCL-B caused the opposite effects. BCL-B inhibited the phosphorylation of Parkin (a key regulator of mitophagy) and directly bound phospho-Parkin. Altogether, enhanced mitophagy promotes apoptosis in HSCs during the reversal of hepatic fibrosis. BCL-B suppresses mitophagy in HSCs by binding and suppressing phospho-Parkin, thereby inhibiting apoptosis. BCL-B-dependent mitophagy is a new pathway for the regulation of apoptosis in HSCs during the regression of hepatic fibrosis.


Assuntos
Apoptose , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Animais , Linhagem Celular , Células Cultivadas , Cirrose Hepática/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
7.
BMC Gastroenterol ; 18(1): 100, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29954324

RESUMO

BACKGROUND: Pneumatosis cystoides intestinalis (PCI) is characterized by gas-filled cysts in the intestinal submucosa and subserosa. There are few reports of PCI occurring in duodenum and rectum. Here we demonstrated four different endoscopic manifestations of PCI and three cases with intestinal stricture all were successfully managed by medical conservative treatment. CASE PRESENTATION: There are 6 cases of PCI with varied causes encountered, in which the etiology, endoscopic features, treatment methods and prognosis of patients were studied. One case was idiopathic, while the other one case was caused by exposing to trichloroethylene (TCE), and the remaining four cases were secondary to diabetes, emphysema, therioma and diseases of immune system. Of the six patients, all complained of abdominal distention or diarrhea, three (50%) reported muco-bloody stools, two (33.3%) complained of abdominal pain. In four other patients, PCI occurred in the colon, especially the sigmoid colon, while in the other two patients, it occurred in duodenum and rectum. Endoscopic findings were divided into bubble-like pattern, grape or beaded circular forms, linear or cobblestone gas formation and irregular forms. After combination of medicine and endoscopic treatment, the symptoms of five patients were relieved, while one patient died of malignant tumors. CONCLUSION: PCI endoscopic manifestations were varied, and radiology combined with endoscopy can avoid misdiagnosis. The primary bubble-like pattern can be cured by endoscopic resection, while removal of etiology combined with drug therapy can resolve majority of secondary cases, thereby avoiding the adverse risks of surgery.


Assuntos
Colo/patologia , Duodeno/patologia , Pneumatose Cistoide Intestinal/patologia , Reto/patologia , Adulto , Idoso , Endoscopia Gastrointestinal , Feminino , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/terapia , Masculino , Pessoa de Meia-Idade , Pneumatose Cistoide Intestinal/complicações , Pneumatose Cistoide Intestinal/etiologia , Pneumatose Cistoide Intestinal/terapia , Radiografia Abdominal , Tomografia Computadorizada por Raios X
8.
J Foot Ankle Surg ; 57(4): 689-693, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29631972

RESUMO

Cutaneous melanoma is a highly malignant skin tumor, and in China, the planta pedis is a commonly involved site. The sites of plantar melanomas are a challenge to reconstruct after wide excision. Our experience with surgical management of melanomas was based on the 4 different anatomic subunits of the planta pedis. From January 1, 2002 to December 31, 2016, 35 patients who had had plantar melanoma had undergone surgical treatment in our clinic. The tumor locations were as follows: the toe in 6, the ball of the foot in 5, the arch in 15, and the heel in 9. Surgical management involved extended resection of the tumor, repair of defects with skin grafts or flaps, and inguinal lymphadenectomy. The skin flaps included a residual toe flap, an anterograde or retrograde medial plantar flap, and a retrograde sural neurocutaneous vascular flap. Of the 35 cases of flaps and skin grafts, 33 (94.29%) survived, and the wounds had healed by first intention. After a follow-up period of 6 months to 7 years, 24 patients (68.57%) were free of local and systemic disease and 30 patients (85.71%) were ambulatory using shoes, and all the flaps and skin grafts showed a good appearance. The personalized surgical treatments we used for melanoma in the planta pedis resulted in overall satisfactory outcomes and adequate disease clearance, and allowed the patients to resume normal lives. The function of the foot was maintained or restored to the greatest possible degree, and the patients' quality of life improved postoperatively.


Assuntos
Procedimentos Cirúrgicos Dermatológicos , , Melanoma/cirurgia , Neoplasias Cutâneas/cirurgia , Retalhos Cirúrgicos , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Resultado do Tratamento , Suporte de Carga , Adulto Jovem
9.
Medicine (Baltimore) ; 96(37): e8057, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28906399

RESUMO

Bacterial infections are an important cause of mortality in liver failure. However, the type of infection, predictors of infection, and their impact on outcomes in patients with acute-on-chronic liver failure (ACLF) are limited.A total of 389 patients with ACLF were admitted in this retrospective, corhort study. Once admitted, clinical data including first infection site, type (community-acquired, healthcare-associated, or nosocomial), and second infection occurrence during hospitalization were collected. The outcome was mortality within 90 days. Multivariable logistic regression models were preformed to predict second infection development and 90-day mortality. Survival probability curves were calculated by the Kaplan-Meier method.Among 389 patients, 316 (81.2%) patients had infection. The 90-day mortality of patients with and without infection was 52.2% and 16.4%, respectively (P <.001). The most common first infection was healthcare associated (51.3%), followed by nosocomial (30.1%) and community-acquired infections (18.7%). Respiratory tract infection, spontaneous bacterial peritonitis, and urinary tract infection were most prevalent. Gram-positive organism was more frequently seen than gram-negative organisms. Of note, fungi accounted for 15.9% of the total infection cases. During hospitalization, 26.6% patients developed second infections. The 90-day mortality of patients developed or did not develop a second infection were 67.9% and 46.6%, respectively (P <.001). Independent predictors of 90-day mortality in infected patients with ACLF were age, white blood cell (WBC) count, model for end-stage liver disease (MELD) score, hepatic encephalopathy (HE), and second infection.Infections (regardless of first or second infection) can increase the 90-day mortality significantly in patients with ACLF. And age, WBC count, MELD score, HE, and the presence of second infection are independent risk factors affecting 90-day mortality in patients with ACLF showing infection.


Assuntos
Insuficiência Hepática Crônica Agudizada/complicações , Insuficiência Hepática Crônica Agudizada/mortalidade , /mortalidade , Insuficiência Hepática Crônica Agudizada/terapia , Feminino , Hospitais , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
10.
Cancer Sci ; 108(9): 1746-1756, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28618124

RESUMO

Piwi-interacting RNAs (piRNAs), a novel class of small non-coding RNAs, were first discovered in germline cells and are thought to silence transposons in spermatogenesis. Recently, piRNAs have also been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. However, the function of piR-823 in colorectal cancer (CRC) remains unclear. Here, we first found that piR-823 was significantly upregulated in CRC tissues compared with its expression in the adjacent tissues. Inhibition of piR-823 suppressed cell proliferation, arrested the cell cycle in the G1 phase and induced cell apoptosis in CRC cell lines HCT116 and DLD-1, whereas overexpression of piR-823 promoted cell proliferation in normal colonic epithelial cell line FHC. Interestingly, Inhibition of piR-823 repressed the expression of heat shock protein (HSP) 27, 60, 70. Furthermore, elevated HSPs expression partially abolished the effect of piR-823 on cell proliferation and apoptosis. In addition, we further demonstrated that piR-823 increased the transcriptional activity of HSF1, the common transcription factor of HSPs, by binding to HSF1 and promoting its phosphorylation at Ser326. Our study reveals that piR-823 plays a tumor-promoting role by upregulating phosphorylation and transcriptional activity of HSF1 and suggests piR-823 as a potential therapeutic target for CRC.


Assuntos
Transformação Celular Neoplásica/metabolismo , Neoplasias Colorretais/metabolismo , Proteínas de Ligação a DNA/fisiologia , Regulação Neoplásica da Expressão Gênica , RNA Interferente Pequeno/fisiologia , Fatores de Transcrição/fisiologia , Apoptose , Proliferação de Células , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Células HCT116 , Fatores de Transcrição de Choque Térmico , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Ligação Proteica , Processamento de Proteína Pós-Traducional , Transcrição Genética , Ativação Transcricional , Regulação para Cima
11.
Transl Res ; 182: 88-102, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28034761

RESUMO

Bile acids stimulate intestinal epithelial proliferation in vitro. We sought to investigate the role of the bile acid receptor TGR5 in the protection of intestinal epithelial proliferation in obstructive jaundice. Intestinal tissues and serum samples were obtained from patients with malignant obstructive jaundice and from bile duct ligation (BDL) rats. Intestinal permeability and morphological changes in the intestinal mucosa were observed. The functions of TGR5 in cell proliferation in intestinal epithelial injury were determined by overexpression or knockdown studies in Caco-2 and FHs 74 Int cells pretreated with lipopolysaccharide (LPS). Internal biliary drainage was superior to external biliary drainage in recovering intestinal permeability and mucosal histology in patients with obstructive jaundice. In BDL rats, feeding of chenodeoxycholic acid (CDCA) decreased intestinal mucosa injury. The levels of PCNA, a marker of proliferation, increased in response to CDCA feeding and were paralleled by elevated TGR5 expression. CDCA upregulated TGR5 expression and promoted proliferation in Caco-2 and FHs 74 Int cells pretreated with LPS. Overexpression of TGR5 resulted in increased PCNA, cell viability, EdU incorporation, and the proportion of cells in S phase, whereas knockdown of TGR5 had the opposite effect. Our data indicate that bile acids promote intestinal epithelial cell proliferation and decrease mucosal injury by upregulating TGR5 expression in obstructive jaundice.


Assuntos
Células Epiteliais/metabolismo , Células Epiteliais/patologia , Mucosa Intestinal/lesões , Mucosa Intestinal/metabolismo , Icterícia Obstrutiva/metabolismo , Icterícia Obstrutiva/patologia , Receptores Acoplados a Proteínas-G/metabolismo , Idoso , Animais , Ductos Biliares/efeitos dos fármacos , Ductos Biliares/patologia , Biomarcadores/sangue , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Ácido Quenodesoxicólico/farmacologia , Células Epiteliais/efeitos dos fármacos , Feminino , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Icterícia Obstrutiva/sangue , Ligadura , Lipopolissacarídeos , Masculino , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
12.
Mol Carcinog ; 56(3): 1137-1149, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27770580

RESUMO

BCL2L10 is an apoptosis-related member of the BCL-2 protein family. The role of BCL2L10 in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. This study was aimed to investigate the function and underlying mechanisms of BCL2L10 in HCC. BCL2L10 expression in human HCC and corresponding adjacent normal tissues was investigated by quantitative real-time PCR and Western blot. The biological functions of BCL2L10 in HCC cell lines were determined by cell viability, colony formation, cell apoptosis, cell cycle, and cell metastasis assays, and in vivo by tumorigenicity and lung metastasis assays in nude mice. Human cancer pathway PCR array was employed to explore the genes regulated by BCL2L10 in HCC. BCL2L10 was down-regulated in human HCC tissues compared to their adjacent non-tumor tissues. Ectopic expression of BCL2L10 in HepG2 and Huh7 cells suppressed cell growth as evidenced by cell viability and colony formation assay, and induced cell apoptosis. HCC cells transfected with BCL2L10 revealed an increased cell proportion arrested at G2/M phase, concomitant with a reduction in the cell proportion in S-phase as compared with control cells. Additional, BCL2L10 repressed cell migration and angiogenesis. Over-expression of BCL2L10 also restrained the tumorigenecity and lung metastasis capacity in nude mice. The activation of JAK-STAT3 signaling was suppressed by BCL2L10 in HCC. BCL2L10 was down-regulated in human HCC tissues compared to adjacent normal tissues. BCL2L10 suppressed HCC progression through inhibiting cell growth and metastasis. Thus, BCL2L10 functions as a tumor-suppressor in HCC. © 2016 Wiley Periodicals, Inc.


Assuntos
Carcinoma Hepatocelular/patologia , Regulação para Baixo , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , Metástase Neoplásica , Transplante de Neoplasias , Transdução de Sinais
14.
Dig Dis Sci ; 61(9): 2522-34, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27146412

RESUMO

BACKGROUND/AIM: Obstructive jaundice (OJ) is frequently complicated by infections and has been associated with increased bacterial translocation, intestinal epithelial hyperpermeability, and oxidative stress, but the mechanism remains unclear. The potential effect of resveratrol (Res) on modifying intestinal epithelial dysfunction was evaluated both in vitro and in vivo. METHODS: Caco-2 cells (in vitro) and male Wistar rats (n = 60; in vivo) were used to evaluate the role of Res on intestinal epithelial dysfunction. Hydrogen peroxide was used to induce oxidative stress in the Caco-2 cells. In bile duct-ligated group, OJ was successfully established on Day 7 after bile duct ligation, whereas sham-operated and vehicle-treated rats served as controls. Western blot and RT-qPCR were performed to analyze TJ proteins expression in epithelium isolated from rat intestine. RESULTS: Intestinal hyperpermeability was associated with decreased expression and phosphorylation of occludin and zonula occluden (ZO-1), but increased oxidation in Caco-2 cells and the intestinal epithelium. Res treatment increased the epithelial expression and phosphorylation of occludin and ZO-1 in a concentration-dependent manner. Moreover, Res which protected Caco-2 cells from H2O2-induced oxidative damage clearly reduced malondialdehyde level and intracellular reactive oxygen species accumulation, but increased the expression levels of superoxide dismutase and heme oxygenase-1 (HO-1). Further studies showed that Res also inhibited H2O2-induced protein kinase C activity and p38 phosphorylation. Interestingly, these effects of Res were abolished by the HO-1 inhibitor zinc protoporphyrin or knockdown of HO-1 by siRNA. CONCLUSIONS: Res protected gut barrier function possibly by initiating HO-1-dependent signaling which is essential for common expression of key tight junction proteins. It also provides a rationale to develop Res clinical applications of intestinal disorders.


Assuntos
Antioxidantes/farmacologia , Heme Oxigenase-1/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Icterícia Obstrutiva/genética , Estresse Oxidativo/efeitos dos fármacos , Estilbenos/farmacologia , Junções Íntimas/efeitos dos fármacos , Animais , Ductos Biliares/cirurgia , Western Blotting , Células CACO-2 , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Icterícia Obstrutiva/metabolismo , Ligadura , Masculino , Malondialdeído/metabolismo , Ocludina/efeitos dos fármacos , Ocludina/metabolismo , Permeabilidade/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteína Quinase C/efeitos dos fármacos , Proteína Quinase C/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Resveratrol , Junções Íntimas/metabolismo , Regulação para Cima , Proteína da Zônula de Oclusão-1/efeitos dos fármacos , Proteína da Zônula de Oclusão-1/metabolismo
15.
Dig Dis Sci ; 61(7): 1961-71, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26879903

RESUMO

BACKGROUND: Astrocyte elevated gene-1 (AEG-1) is a positive regulator of tumorigenesis and a valuable prognostic marker of a diverse array of cancers, including liver cancer; however, the relationship between AEG-1 and hepatic fibrogenesis is not known. OBJECTIVE: The objective of this study was to explore the expression of AEG-1 during hepatic fibrogenesis and determine how AEG-1 regulates the profibrogenic phenotype of hepatic stellate cells (HSCs). METHODS: The levels of AEG-1 were monitored in the fibrotic livers and transforming growth factor-ß (TGF-ß)- or lipopolysaccharide (LPS)-stimulated HSCs. The expression of AEG-1 was knocked down by lentivirus-mediated short hairpin RNA in HSCs, and collagen expression, proliferation assays, apoptosis induction studies, and migration assays were simultaneously conducted in vitro. RESULTS: AEG-1 expression was increased in the fibrotic livers. At the cellular level, TGF-ß or LPS stimulation, which caused HSC activation, induced AEG-1 expression in HSC-T6 and primary rat HSCs (P < 0.05). Knockdown of AEG-1 inhibited collagen I and α-smooth muscle actin expression (P < 0.05), reduced cell proliferation (P < 0.05) and motility (P < 0.05), and induced cell apoptosis (P < 0.05) in HSCs. This antifibrotic effect caused by lack of AEG-1 was associated with the inactivation of PI3K/Akt and the mitogen-activated protein kinase pathway. CONCLUSIONS: Knockdown of AEG-1 suppressed the activation of HSCs by modulating the phenotype and inducing apoptosis. AEG-1 might be a potential target in treatment of hepatic fibrosis.


Assuntos
Células Estreladas do Fígado/fisiologia , Animais , Apoptose , Ductos Biliares/cirurgia , Ciclo Celular , Linhagem Celular , Proliferação de Células , Dimetilnitrosamina/toxicidade , Regulação da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Ligadura , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/etiologia , Masculino , Ratos , Ratos Sprague-Dawley , Regulação para Cima
17.
Phlebology ; 31(6): 397-402, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26085476

RESUMO

BACKGROUND: Venous malformation (VM) is a common vascular malformation in soft tissue. Surgical management plays an important role in its treatment. The location, extent, and adjacent anatomy of the lesion are crucial information for the safety of operation. This study introduces the application of magnetic resonance imaging and percutaneous sinus angiography/three-dimensional computed tomography imaging in gathering above information. METHODS: A retrospective analysis was made in the patients with venous malformation from January 2012 to June 2014 in our clinic. All patients underwent magnetic resonance imaging and percutaneous sinus angiography/three-dimensional computed tomography imaging. The location, extent of the lesion, its draining veins, and the relationship with around tissues were showed. Surgical management was carried out in the lesions which were well defined, located in the superficial fascia without important vessels and nerves across it. The wound was repaired by skin flap or skin graft. RESULTS: A total of 13 patients underwent complete surgical removal of the lesions, including five type I venous malformations and eight type II venous malformations. Ten lesions were removed by undermining dissection, and the wound was repaired by the undermined flap. Three superficial lesions were removed together with the skin over it, and the wound was repaired by the skin graft. In the six months to two years of follow-up period, none of the recurrence of the lesion was observed. CONCLUSION: Magnetic resonance imaging and percutaneous sinus angiography/three-dimensional computed tomography imaging can display abundant morphological details of venous malformation, which are helpful for the surgical management.


Assuntos
Angiografia por Ressonância Magnética , Tomografia Computadorizada por Raios X , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/cirurgia , Adulto , Humanos , Masculino , Estudos Retrospectivos
18.
Int J Clin Exp Med ; 8(6): 10006-10, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26309243

RESUMO

Kasabach-Merritt phenomenon (KMP) is life-threatening, charactered by the profound thrombocytopenia and consumptive coagulopathy associated with vascular tumors. The therapy of KMP still remains challenging. In this study, we retrospectively analyzed the clinical data of KMP treated in Nanjing Children's Hospital and Jinling Hospital, China, and brief reviewed the literature on KMP. From Jan. 2005 to Dec. 2014, a total of 19 cases of KMP were enrolled into this study. Laboratory results showed that seven patients had typical disseminated intravascular coagulation (DIC), and others were atypical DIC. CT scanning showed the low-density tumor with obvious intensification in enhanced scanning, and the large distorted arteries in association with the tumor. After the admission, the patients received the infusion of platelets and the applying of dipyridamole, steroids, and other necessary drugs. Eight patients underwent complete surgical removal of the tumor, or partial removal with subsequent chemotherapy of vincristine. Three patients underwent only the chemotherapy of vincristine. Eight patients underwent the intralesional injection of absolute ethanol. Pathological examination showed eighteen samples were kaposiform hemangioendothelioma, and one tufted agioma. In our cases, six patients died from extensive hemorrhage and subsequent multiple organ failure. The others survived. In conclusion, KMP in Chinese children has typical symptoms. Kaposiform hemangioendothelioma is the most frequent vascular tumor associated with KMP. The individual treatments with surgical management, chemotherapy with vincristine, and intralesional injection of absolute ethanol can achieve good results in most of the patients with KMP.

19.
Int J Clin Exp Med ; 8(4): 5245-53, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26131098

RESUMO

Neurofibroma, a common benign tumor in soft tissue, continues to grow, and often appears to be giant. In this study, we retrospectively analyzed the surgical treatment of 26 patients with giant neurofibromas in our clinic in the past 10 years from Jan. 2004 to Dec. 2013. The tumors were located in the head (n = 10), trunk (n = 9), limbs (n = 5), and multi-sites (n = 2). According to the location and extent of the lesion, as well as the adjacent anatomy, surgical management was performed to partially (n = 15) or almost completely (n = 11) resect the tumor. The wounds were repaired by skin flap or skin graft. Among them, one child with a giant tumor in the scalp underwent three times of skin expander treatment, and acquired complete removal of the tumor finally without baldness. Eleven cases underwent the interventional embolization of tumor's nutrient arteries, which successfully reduced the bleeding in operation. Most of the skin flap and skin graft survived well. After operation, the appearance of the patients and the function of the limbs were improved largely. In conclusion, for the giant neurofibroma, surgical treatment effectively reduces the tumor burden, rehabilitates the appearance and function, and so improves the quality of life. Skin expandor and interventional embolization of nutrient artery can be used when appropriate.

20.
J Craniofac Surg ; 26(5): e405-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26102538

RESUMO

OBJECTIVES: Neurofibroma, a common benign tumor in soft tissue, continues to grow, so it often appears to be giant. Surgical management of giant neurofibroma is a challenge due to the risk of excessive bleeding. Embolization of tumor's nutrient artery may reduce the blood loss in operation. This study introduces the surgical management of giant scalp neurofibroma with preoperative ultra-selective embolization of nutrient artery. METHODS: From January 2006 to December 2013, 9 patients with giant scalp neurofibroma were enrolled into the study. Digital subtraction angiography (DSA) showed tumor's nutrient artery. Ultra-catheter was inserted into the nutrient artery and its branches as close as possible to the tumor. Then ultra-selective embolization was performed with gelatin sponge particles. Surgical removal of tumor was performed in 3 days after embolization. The wound was repaired by skin graft. RESULTS: All of the 9 patients underwent successful DSA and ultra-selective embolization. Among them, occipital artery was embolized in 3 patients (left side in 1 patient and right side in 2 patients). Both occipital artery and superficial temporal artery were embolized in 6 patients (left side in 2 patients, right side in 3 patients, and both side in 1 patient). No complications, such as ectopic embolism, occurred in the patients. All of the tumors were resected completely without blood transfusion. The skin graft survived very well on the wounds. CONCLUSIONS: Preoperative ultra-selective embolization of nutrient artery is a feasible, safe, and effective method to reduce the blood loss in operation and facilitate the surgical management of giant scalp neurofibroma.


Assuntos
Embolização Terapêutica/métodos , Neoplasias de Cabeça e Pescoço/cirurgia , Neurofibroma/cirurgia , Couro Cabeludo/cirurgia , Neoplasias Cutâneas/cirurgia , Adolescente , Adulto , Angiografia Digital/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Criança , Feminino , Esponja de Gelatina Absorvível/uso terapêutico , Neoplasias de Cabeça e Pescoço/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neurofibroma/irrigação sanguínea , Neurofibroma/terapia , Osso Occipital/irrigação sanguínea , Couro Cabeludo/patologia , Neoplasias Cutâneas/irrigação sanguínea , Neoplasias Cutâneas/terapia , Transplante de Pele/métodos , Artérias Temporais/patologia , Adulto Jovem
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