RESUMO
Endoscopic retrograde cholangiopancreatography (ERCP) combined with laparoscopic cholecystectomy plays an important role in the treatment of cholecystolithiasis combined with choledocholithiasis; however, there is no unified standard for the interval of ERCP before laparoscopic cholecystectomy. We conducted a literature search, data extraction and meta-analysis on this topic. Twelve articles with 1142 patients were included, including 567 patients in the E-laparoscopic cholecystectomy group (laparoscopic cholecystectomy performed within 72â h after ERCP) and 575 patients in the D-laparoscopic cholecystectomy group (laparoscopic cholecystectomy performed 72â h after ERCP). The results showed that: compared with the D-laparoscopic cholecystectomy group, the duration of cholecystectomy was shorter in the E-laparoscopic cholecystectomy group [weighted mean difference (WMD)â =â -16.18, 95% confidence interval (CI) (-22.27 to -10.08), P â <â 0.00001], and the postoperative hospitalization was shorter [WMDâ =â -1.24, 95% CI (-1.98 to -0.50), P â <â 0.0001]. There were fewer complications [odds ratio (OR)â =â 0.25, 95% CI (0.39-0.62), P â <â 0.0001], lower conversion rate [ORâ =â 0.39, 95% CI (0.21-0.71), P â =â 0.002], lower high sensitivity C-reactive protein at 3â days after surgery [WMDâ =â -8.76, 95% CI (-12.59 to -4.93), P â <â 0.00001], and fewer neutrophils in the ampulla of gallbladder specimen [WMDâ =â -4.21, 95% CI (-4.55 to -3.88), P < 0.00001]. Therefore, in the treatment of cholecystolithiasis combined with choledocholithiasis by laparoscopic cholecystectomy within 72â h after ERCP, the degree of inflammation before and after surgery is less, the operation time and hospital stay are shortened, the postoperative complications and the conversion rate are reduced, which is a more appropriate time for surgery.
Assuntos
Colecistectomia Laparoscópica , Colecistolitíase , Coledocolitíase , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Coledocolitíase/diagnóstico por imagem , Coledocolitíase/cirurgia , Coledocolitíase/complicações , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/métodos , Colecistolitíase/complicações , Colecistolitíase/cirurgia , Esfinterotomia EndoscópicaRESUMO
OBJECTIVE: To conduct a systematic review of efficacy and security of fast track surgery (FTS) in laparoscopic radical gastrectomy for gastric cancer. METHODS: We searched PubMed, Embase, and Cochrane Library Databases and supplemented by other searches to collect randomized controlled trials (RCTs) on the comparison of fast track surgery combined with laparoscopy versus laparoscopy separately used in radical gastrectomy for gastric cancer before December 2016. After screening for inclusion, data extraction, and quality assessment, meta-analysis was conducted by the Review Manager 5.3 software. RESULTS: A total of 6 RCTs, involving 464 patients, were included. There were 232 patients in the FTS group and conventional care group separately. Compared with the conventional care group, patients of FTS group had shorter postoperative hospital stay [WMDâ¯=â¯-1.85, 95%CI: (-2.60, -1.11), Pâ¯<â¯.00001], earlier first flatus [WMDâ¯=â¯-9.33, 95%CI: (-13.74, -4.91), Pâ¯<â¯.0001], lower level of C-reactive protein (CRP) at postoperative day 4 [WMDâ¯=â¯-13.94, 95%CI: (-22.74, -5.15), Pâ¯=â¯.002], and less hospitalization fees [SMDâ¯=â¯-1.12, 95%CI: (-2.07, -0.18), Pâ¯=â¯.02]. There were no significant differences in operation time, intraoperative blood loss, and postoperative complications between the two groups. CONCLUSION: Based on current evidence, the FTS protocol is safe and effective in laparoscopic radical gastrectomy for gastric cancer. Due to the limitations of our study, further larger and multicenter studies are needed to validate our findings.
Assuntos
Gastrectomia/métodos , Laparoscopia/métodos , Neoplasias Gástricas/cirurgia , Proteína C-Reativa , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/economia , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/economia , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Chewing gum, as an alternative to sham feeding, had been shown to hasten the recovery of gut function following abdominal surgery. However, conclusions remained contradictory. We sought to conduct an updated meta-analysis to evaluate the efficacy of gum chewing in alleviating ileus following colorectal surgery. METHODS: We searched PubMed, EMBASE, and Cochrane Library Databases through February 2017 to identify randomized controlled trials (RCTs) evaluating the efficacy of the additional use of chewing gum following colorectal surgery. After screening for inclusion, data extraction, and quality assessment, meta-analysis was conducted by the Review Manager 5.3 software. The outcomes of interest were the time to first flatus, time to first bowel movement, length of hospital stay, and some clinically relevant parameters. We also performed subgroup analyses according to the type of surgical approaches or on trials that adopted enhanced recovery after surgery (ERAS) protocol or sugared gum. RESULTS: A total of 18 RCTs, involving 1736 patients, were included. Compared with standardized postoperative care, Chewing gum resulted in a shorter passage to first flatus [WMD = -8.81, 95%CI: (-13.45, -4.17), P = 0.0002], earlier recovery of bowel movement [WMD = -16.43, 95%CI: (-22.68, -10.19), P < 0.00001], and a reduction in length of hospital stay [WMD = -0.89, 95%CI: (-1.72, -0.07), P = 0.03]. Chewing gum was also associated with a lower risk of postoperative ileus [OR = 0.41, 95%CI: (0.23, 0.73), P = 0.003]. No evidence of significant advantages in overall postoperative complication, nausea, vomiting, bloating, readmission and reoperation towards the addition of chewing gum was observed. Subgroup analyses all favored gum chewing. However, the findings are hampered by the significant heterogeneity between trials. CONCLUSIONS: Based on current evidence, chewing gum offers an inexpensive, well-tolerated, safe and effective method to ameliorate ileus following colorectal surgery. However, tightly controlled, randomized and considerably larger multicenter trials are warranted to further validate our findings.
Assuntos
Goma de Mascar , Colo/cirurgia , Íleus/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Reto/cirurgia , Humanos , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Eupafolin is a flavonoid extracted from the common sage herb which has been used in China as traditional medicine. Previous studies had reported that eupafolin had antioxidative, anti-inflammatory and antitumor effects. However, the function and the mechanism of eupafolin to exert its antitumor activity, especially its effect on tumor angiogenesis, have not been elucidated. Herein, we showed that eupafolin significantly inhibited vascular endothelial growth factor (VEGF)-induced cell proliferation, migration and tube formation of human umbilical vascular endothelial cells (HUVECs) in a dose-dependent manner. Meanwhile, the new blood microvessels induced by VEGF in the matrigel plug were also substantially suppressed by eupafolin. The results of HCC xenograft experiments demonstrated eupafolin remarkably inhibited tumor growth and tumor angiogenesis in vivo, suggesting the antitumor activity exerted by eupafolin was closely correlated with its potency on tumor angiogenesis. Mechanism investigations revealed that eupafolin significantly blocked VEGF-induced activation of VEGFR2 in HUVEC cells as well as its downstream signaling pathway. In addition to the effect on endothelial cells, through inhibiting Akt activity in tumor cells, VEGF secretion in HepG2 was dramatically decreased after eupafolin treatment. Our study was the first to report the activity of eupafolin against tumor angiogenesis as well as the underlying mechanism by which eupafolin to exert its anti-angiogenic activity.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Flavonas/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Animais , Proliferação de Células/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Neovascularização Patológica/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Hexokinase-2(HK-2) plays dual roles in glucose metabolism and mediation of cell apoptosis, making it an attractive target for cancer therapy. Chrysin is a natural flavone found in plant extracts which are widely used as herb medicine in China. In the present study, we investigated the antitumor activity of chrysin against hepatocellular carcinoma (HCC) and the role of HK-2 played for chrysin to exert its function. METHODS: The expression of HK-2 in HCC cell line and tumor tissue was examined by western blotting and immunohistochemistry staining. The activities of chrysin against HCC cell proliferation and tumor glycolysis were investigated. Chrysin-induced apoptosis was analyzed by flow cytometry. The effect of chrysin on HK-2 expression and the underlying mechanisms by which induced HCC cell apoptosis were studied. In HK-2 exogenous overexpression cell, the changes of chrysin-induced cell apoptosis and glycolysis suppression were investigated. HCC cell xenograft model was used to confirm the antitumor activity of chrysin in vivo and the effect on HK-2 was tested in chrysin-treated tumor tissue. RESULTS: In contrast with normal cell lines and tissue, HK-2 expression was substantially elevated in the majority of tested HCC cell lines and tumor tissue. Owing to the decrease of HK-2 expression, glucose uptake and lactate production in HCC cells were substantially inhibited after exposure to chrysin. After chrysin treatment, HK-2 which combined with VDAC-1 on mitochondria was significantly declined, resulting in the transfer of Bax from cytoplasm to mitochondria and induction of cell apoptosis. Chrysin-mediated cell apoptosis and glycolysis suppression were dramatically impaired in HK-2 exogenous overexpression cells. Tumor growth in HCC xenograft models was significantly restrained after chrysin treatment and significant decrease of HK-2 expression was observed in chrysin-treated tumor tissue. CONCLUSION: Through suppressing glycolysis and inducing apoptosis in HCC, chrysin, or its derivative has a promising potential to be a novel therapeutic for HCC management, especially for those patients with high HK-2 expression.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Flavonoides/administração & dosagem , Glicólise/efeitos dos fármacos , Hexoquinase/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Camundongos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A disintegrin and metallopeptidase with thrombospondin motif type 8 (ADAMTS8), a member of the ADAMTS family, was discovered as a novel angiogenesis inhibitor. We analyzed the expression and methylation of ADAMTS8 in primary gastric tumors and gastric cancer cell lines. We also examined the relationship between ADAMTS8 expression and methylation and clinicopathologic features. The results showed that the significant downregulation of ADAMTS8 mRNA expression was observed in gastric cancer cell lines and tissues, and its expression was related to invasive depth and lymph node metastasis. CpG was hypermethylated in gastric cancer cell lines MKN45, MGC803, and BGC823, as well as primary gastric cancer specimens. ADAMTS8 mRNA expression was significantly lower in methylated primary gastric tumors. A significant association was found between ADAMTS8 methylation status and lymph node metastasis in primary gastric cancer. Moreover, ADAMTS8 expression was upregulated in the gastric cancer cell lines MGC803, BGC823, and MKN45 after treatment with 5-aza-2'-deoxycytidine. Thus, our results demonstrate that expression of ADAMTS8 mRNA is significantly decreased and DNA methylation is frequent in gastric cancer. ADAMTS8 hypermethylation is associated with decreased expression in gastric cancer and may play an important role in the invasion and metastasis of gastric cancer.
Assuntos
Proteínas ADAMTS/genética , Metilação de DNA/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/genética , Proteínas ADAMTS/metabolismo , Idoso , Azacitidina/farmacologia , Linhagem Celular Tumoral , Metilação de DNA/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND/AIMS: MafB, a member of the Maf transcription factor family, plays a key role in the regulation of pancreatic alpha and beta cell differentiation. However, its function in the control of cancer cell proliferation remains unknown. METHODS: The mRNA and protein expression levels of MafB in hepatocellular carcinoma tissues and adjacent non-tumor normal specimens were determined by real-time RT-PCR and Western blot, respectively. Report assay was performed to determine whether the regulation of Cyclin D1 by MafB is at the transcriptional level. The binding of MafB to the Cyclin D1 promoter was determined by Chromatin Immunoprecipitation (ChIP) assays. To determine the potential oncogenic effects of MafB in vivo, HepG2 cells transfected with adenovirus containing empty vector or MafB were injected subcutaneously to the skin under the front legs of the nude mice. RESULTS: In the current study, we showed that MafB was markedly up-regulated in hepatocellular carcinoma (HCC) tissues and cells. Enforced overexpression of MafB enhanced, while its deficiency inhibited HCC cell proliferation. Mechanistically, Cyclin D1, an important regulator of cell cycle progression, was identified as a direct transcriptional target of MafB. Consistently, knockdown of Cyclin D1 largely attenuated the proliferative roles of MafB in HCC cells. Importantly, MafB overexpression significantly promoted cancer cell growth in mice. CONCLUSIONS: Collectively, our results identified a novel HCC regulatory pathway involving MafB and Cyclin D1, the dysfunction of which drives proliferative character in HCC.
Assuntos
Carcinoma Hepatocelular/genética , Proliferação de Células/genética , Ciclina D1/genética , Neoplasias Hepáticas/genética , Fator de Transcrição MafB/genética , Regulação para Cima , Animais , Western Blotting , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Ciclina D1/metabolismo , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Fator de Transcrição MafB/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Regiões Promotoras Genéticas/genética , Ligação Proteica , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante HeterólogoRESUMO
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) represents the most common type of liver cancer. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1), an atypical member of the nuclear receptor family due to lack of classical DNA-binding domains, has been known for its fundamental roles in the development, especially in the sex determination and steroidogenesis. Previous studies also showed that DAX-1 played a critical role in endocrine and sex steroid-dependent neoplasms such as adrenocortical, pituitary, endometrial, and ovarian tumors. However, its biological roles in the development of HCC remain largely unexplored. METHODS: Real-time PCR and Western blot were used to detect the expression of DAX-1 in HCC tissues and cell lines. Immunoprecipitation (IP) assay was used to show the interaction between DAX-1 and ß-Catenin. Small interfering RNA (siRNA) was used to silence the expression of DAX-1. BrdU incorporation and Cell-cycle assays were used to detect the role of DAX-1 in HCC cells proliferation. Migration and invasion assays were carried out to test the metastasis ability of DAX-1 in HCC cells. RESULTS: In the present study, we found that mRNA and protein levels of DAX-1 were down-regulated in HCC tissues and cell lines. Furthermore, overexpression of DAX-1 could inhibit while its knockdown using small interfering RNA promoted cell proliferation in several HCC cell lines. At the molecular level, we demonstrated that DAX-1 could interact with ß-Catenin and attenuate its transcriptional activity. CONCLUSION: Therefore, our results suggest a previously unknown DAX-1/ß-Catenin molecular network controlling HCC development.
Assuntos
Carcinoma Hepatocelular/patologia , Proliferação de Células , Receptor Nuclear Órfão DAX-1/fisiologia , Neoplasias Hepáticas/patologia , Transcrição Gênica , beta Catenina/genética , Linhagem Celular Tumoral , Regulação para Baixo , Humanos , Invasividade Neoplásica , Metástase NeoplásicaRESUMO
Multiple studies have shown that steroid receptor coactivator-3 (SRC-3) is upregulated and promotes cell proliferation in several human cancers, including breast, lung, and prostate carcinoma. However, its molecular determinants remain largely unexplored. In the current study, by way of informatics software, we found that MicroRNA-195 (miR-195) could negatively regulate protein levels of SRC-3 through targeting its 3'-untranslated region (3'-UTR) in hepatocellular carcinoma (HCC) cells. As a result, miR-195 mimics inhibited while its antisense enhanced SRC-3 protein levels. Furthermore, miR-195 could modulate cell proliferation and tumor growth in vivo and in vitro. Therefore, our results demonstrate a novel molecular mechanism for the dysregulated expression of SRC-3 in hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Coativador 3 de Receptor Nuclear/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Coativador 3 de Receptor Nuclear/metabolismoRESUMO
Capsaicin is the major pungent ingredient in red peppers which is world widely consumed. Except its potent pain relieving efficacy as reported, capsaicin also exerted its antitumor activity in several tumor models. Here, we reported that capsaicin had a profound anti-proliferative effect on human colon cancer cells via inducing cell cycle G0/G1 phase arrest and apoptosis, which was associated with an increase of p21, Bax and cleaved PARP. The underlying mechanism of capsaicin's antitumor potency was mainly attributed to the stabilization and activation of p53. Capsaicin substantially prolonged the half-life of p53 and significantly elevated the transcriptional activity of p53. Through suppressing the interaction between p53 and MDM2, MDM2-mediated p53 ubiquitination was remarkably decreased after capsaicin treatment, which resulted in the stabilization and accumulation of p53. The results of p53-shRNA experiment further demonstrated that p53 knockdown severely impaired the sensitivity of tested cells to capsaicin, G0/G1 phase arrest and the apoptosis induced by capsaicin in p53-knockdown cells was also dramatically decreased, implicating the important role of p53 played in capsaicin's antitumor activity. In summary, our data suggested that capsaicin, or a related analogue, may have a role in the management of human colon cancer.
Assuntos
Capsaicina/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Fitoterapia , Fármacos do Sistema Sensorial/uso terapêutico , Proteína Supressora de Tumor p53/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Capsaicina/farmacologia , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Fármacos do Sistema Sensorial/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismoRESUMO
Many studies were published to examine the association between XRCC3 C241T polymorphism and hepatocellular carcinoma risk, but their results were inconsistent. To assess the association between XRCC3 C241T polymorphism and hepatocellular carcinoma risk more precisely, a meta-analysis was performed. PubMed, Embase and Wanfang databases were searched for relevant case-control studies. Data were extracted, and the pooled odds ratios (OR) with 95 % confidence intervals (95% CI) were calculated. Finally, seven studies comprising 2,288 cases with hepatocellular carcinoma and 3,249 controls were included into the meta-analysis. Overall, there was an obvious association between XRCC3 C241T polymorphism and increased risk of hepatocellular carcinoma (TT versus CC: OR = 3.31, 95% CI 1.52-7.19, P = 0.003; TT versus CC/CT: OR = 3.31, 95% CI 1.81-6.06, P < 0.001). After adjusting for heterogeneity, there was still an obvious association between XRCC3 C241T polymorphism and increased risk of hepatocellular carcinoma (TT versus CC: OR = 1.92, 95 % CI 1.13-3.26, P = 0.016; TT versus CC/CT: OR = 2.10, 95% CI 1.25-3.55, P = 0.005). Overall, there is a significant association between XRCC3 C241T polymorphism and increased risk of hepatocellular carcinoma. Further studies are needed to further assess the association in Caucasians.
Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Humanos , Razão de Chances , Fatores de RiscoRESUMO
Previous published studies suggested that genetic polymorphisms in DNA repair genes could modify the DNA repair capacity and could be associated with pancreatic cancer risk. However, previous studies on the association between X-ray repair cross-complementation group 1 (XRCC1) rs25487 (Arg399Gln) polymorphism and pancreatic cancer risk reported inconsistent results. To obtain a more precise estimation of the association between XRCC1 rs25487 polymorphism and pancreatic cancer risk, we performed a meta-analysis of previous published studies by calculating the pooled odds ratio (OR) with a 95% confidence interval (95% CI). Eight individual studies with 5,542 subjects from six publications were finally included into this meta-analysis. The meta-analysis of total eight studies showed that there was no association between XRCC1 rs25487 polymorphism and pancreatic cancer risk in total population under all four genetic models (Gln versus Arg: OR = 1.10, 95% CI 0.95-1.28, P = 0.199; GlnGln versus ArgArg: OR = 1.15, 95% CI 0.93-1.41, P = 0.191; GlnGln/ArgGln versus ArgArg: OR = 1.10, 95% CI 0.97-1.25, P = 0.127; GlnGln versus ArgArg/ArgGln: OR = 1.12, 95% CI 0.92-1.36, P = 0.253). Subgroup analysis showed that there was no association between XRCC1 rs25487 polymorphism and pancreatic cancer risk in Caucasians, but XRCC1 rs25487 polymorphism was associated with pancreatic cancer risk in Asians (GlnGln/ArgGln versus ArgArg: OR = 1.24, 95% CI 1.01-1.53, P = 0.040). Therefore, the meta-analysis suggests that XRCC1 rs25487 polymorphism is associated with pancreatic cancer risk in Asians. Further studies with more participants are needed to provide a more precise estimation on the association above.
Assuntos
Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Neoplasias Pancreáticas/genética , Polimorfismo de Nucleotídeo Único , Povo Asiático/genética , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Razão de Chances , Neoplasias Pancreáticas/etnologia , Fatores de Risco , População Branca/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
PHA665752 (PHA), a selective small molecule c-Met Inhibitor, potently inhibited HGF-stimulated and constitutive c-Met phosphorylation, as well as HGF and c-Met-driven phenotypes of a variety of tumor cells including hepatocellular carcinoma cells. However, these effects were impaired in c-Met-deficient cancer cells. In the present study, we investigated the potential anti-human c-Met-deficient hepatocellular carcinoma effects of Celastrol, a novel triterpene, and its combination with PHA. Human hepatocellular carcinoma cells BEL-7402 (c-Met-positive) and Huh7 (c-Met-deficient) were treated with different dose of PHA with or without equal dose of Celastrol, and cell growth, cell cycle and apoptosis were evaluated, respectively, by MTT assay, flow cytometry and Caspase3/7 activity. Nude mice bearing Huh7 xenografts were used to assess the in vivo anti-tumor activity. Our results showed that Celastrol at high concentration (>1.0 µM) induced G2/M arrest and apoptosis with the activation of Caspase3/7 in Huh7 cells whereas at low concentration (<1.0 µM) had no obvious effects. Low concentration Celastrol presented significant combined effects with PHA on Huh7 cells and Huh7 xenografts in terms of growth inhibition, migration inhibition and apoptosis induction. These results suggest that Celastrol and its combination with PHA present the therapeutic potential on c-Met-deficient hepatocellular carcinoma, and deserve further preclinical and clinical studies.
Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Indóis/farmacologia , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-met/deficiência , Sulfonas/farmacologia , Triterpenos/farmacologia , Carga Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Indóis/administração & dosagem , Neoplasias Hepáticas/genética , Masculino , Camundongos , Triterpenos Pentacíclicos , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo , Sulfonas/administração & dosagem , Triterpenos/administração & dosagem , Carga Tumoral/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
CXCL16/SR-PSOX is a novel transmembrane-type chemokine, which was also identified as a novel scavenger receptor for oxidized low density lipoprotein. Its receptor CXCR6 expresses on activated CD8(+) T cells, type 1-polarized CD4(+), and constitutively expresses on NKT cells. Moreover, it has been shown that CXCL16 accumulated activated CD8(+) T cells to sites of inflammation. To date, the effect of CXCL16 (SR-PSOX)/CXCR6 on CD8(+) T cells and its role in allograft rejection/acceptance are not well understood. In the current study, we show that rejected allografts showed higher expressions of CXCR6 and CXCL16. More importantly, expression of CXCR6 on CD8(+) T cells was also up-regulated by rejection. However, the blockade of CXCL16(SR-PSOX)/CXCR6 interaction could not inhibit cytotoxic activity of CD8(+) T cells, and therefore, could not prolong the cardiac graft survival time.
Assuntos
Linfócitos T CD8-Positivos/metabolismo , Rejeição de Enxerto/imunologia , Receptores CXCR/metabolismo , Animais , Anticorpos Monoclonais/administração & dosagem , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Linhagem Celular Tumoral , Citotoxicidade Imunológica/efeitos dos fármacos , Rejeição de Enxerto/genética , Rejeição de Enxerto/metabolismo , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Coração , Imunofenotipagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Receptores CXCR/genética , Receptores CXCR/imunologia , Receptores CXCR6 , Baço/patologia , Transplante Homólogo , Regulação para CimaRESUMO
AIMS: To investigate the relations between the formation of pigment gallstone and the function of the intestinal mucosal barrier, as well as the underlying mechanism. METHODS: Eighty guinea pigs were randomly divided into three groups in which they were respectively given normal diet, gallstone-causing diet, and gallstone-formation diet with a supplementary intestinal mucosal protection compound known as glutamine. The model of pigment gallstone was established after 8 weeks of dietary administration. Indices about the function of the intestinal mucosal barrier and bacterial translocation were measured. Clinical cases were divided into three groups: control, cholesterol gallstone, and pigment gallstone, where the levels of plasma diamine oxidase (DAO), plasma endotoxin and the excretion rates of technetium 99m-diethylene triamine pentaacetic acid (99mTC-DTPA) in the urine of each group were measured. RESULTS: In the pigment gallstone group, the level of plasma DAO and endotoxin, the excretory ratio of lactulose and mannitol in urine, the bacterial translocation ratio in the celiac lymph nodes and the activities of beta-glucuronidase increased comparing to the control group. The gallstone-formation rate for the intestinal mucosal protection group (GLN) decreased, and other indices, except the activity of beta-glucuronidase, were all lower than that of gallstone-formation group. In the clinical experiment, the levels of plasma DAO and endotoxin, as well as the excretory rate of 99mTC-DTPA in urine were higher in the patients with gallstones than that in the control group. CONCLUSIONS: The formation of pigment gallstone was related to the abnormal function of the intestinal mucosal barrier. The abnormality in the function of the intestinal mucosal barrier probably induced the formation of gallstone by a bacterial translocation mechanism.
Assuntos
Translocação Bacteriana , Pigmentos Biliares/metabolismo , Cálculos Biliares/metabolismo , Mucosa Intestinal/metabolismo , Amina Oxidase (contendo Cobre)/sangue , Animais , Translocação Bacteriana/efeitos dos fármacos , Bile/enzimologia , Estudos de Casos e Controles , Colesterol/metabolismo , Modelos Animais de Doenças , Endotoxinas/sangue , Feminino , Cálculos Biliares/tratamento farmacológico , Cálculos Biliares/microbiologia , Glucuronidase/metabolismo , Glutamina/farmacologia , Cobaias , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Lactulose/urina , Linfonodos/microbiologia , Masculino , Manitol/urina , Permeabilidade , Projetos Piloto , Compostos Radiofarmacêuticos/urina , Pentetato de Tecnécio Tc 99m/urinaRESUMO
OBJECTIVE: To investigate the relationship between the intestinal barrier function and pigment gallstone formation. METHODS: Ninety Guinea pigs were divided randomly into 3 groups: normal control (CON) group receiving normal forage, pigment gallstone (PS) group receiving pigment gallstone-forming forage, and intestinal mucosa protection group receiving pigment gallstone-forming forage with supplemental glutamine intestinal (GLN), a mucosa protector. The guinea pigs were observed for 8 weeks, the gallstone-forming rate, plasma diamine oxidase ( DAO), serum endotoxin, proportionality of urine lactulose/mannitol, and biliary beta-glucuronidase were detected. PCR was used to detect the bacteria in abdominal lymph node taking 16SrRNA as the target gene common in most bacteria. 32 gallstone patients, 16 with cholesterol gallstone and 16 with pigmental gallstone, and 27 patients with non-gastroenterological diseases, as controls, underwent detection of the plasma DAO and serum endotoxin. Another 109 gallstone patients, 31 with cholesterol gallstone and 78 with pigmental gallstone, and 21 patients with nongastroenterological diseases, as controls, underwent detection of urine technetium-labeled diethylenetriamine-pentaacetate (99mTc-DTPA). RESULTS: The gallstone-forming rate of the guinea pigs of the GLN group was 44.4% was, significantly lower than that of the PS group (73.9%, P < 0.05). The plasma DAO, serum endotoxin levels, proportionality of urine lactulose/mannitol, and activity of biliary beta-glucuronidase of the PS group were all significantly higher than those of the CON group (P < 0.05 or P < 0.01). The plasma endotoxin level of the pigmental GLN group was significantly lower than that of the PS group (P < 0.01). The positive rate of bacteria in abdominal lymph node of the PS group was 80%, significantly higher than those of the CON and GLN groups (30% and 45% respectively, P < 0.01 and P < 0.05). The level of plasma DAO and endotoxin of the pigmental gallstone patients were significantly higher than those of the controls (P < 0.05 and P < 0.01). The urine 99mTc-DTPA excretion rate of gallstone patients was 11.4%, significantly higher than that of the controls (4.7%, P < 0.01). CONCLUSION: Intestinal barrier function is correlated with pigment gallstone forming. Intestinal barrier function disorder may promote pigment gallstone formation through bacteria translocation, endotoxemia, and increase of biliary beta-glucuronidase.
Assuntos
Pigmentos Biliares/metabolismo , Cálculos Biliares/fisiopatologia , Mucosa Intestinal/fisiopatologia , Abdome/microbiologia , Abdome/patologia , Amina Oxidase (contendo Cobre)/sangue , Animais , Bactérias/genética , Bactérias/isolamento & purificação , Sistema Biliar/metabolismo , Sistema Biliar/patologia , Modelos Animais de Doenças , Feminino , Cálculos Biliares/metabolismo , Cálculos Biliares/patologia , Glucuronidase/metabolismo , Cobaias , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Linfonodos/microbiologia , Linfonodos/patologia , Masculino , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genéticaRESUMO
AIM: To detect whether patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux by measuring the radioactivity of Tc99m-labeled diethylene triamine penta-acetic acid (DTPA) in the bile and whether the patients with duodenal-biliary reflux have sphincter of Oddi hypomotility, by measuring the level of plasma and serum gastrin of the patients. Finally to if there is close relationship among sphincter of Oddi hypomotility, duodenal-biliary reflux and gastrointestinal peptides. METHODS: Forty-five patients with a T tube after cholecystectomy and choledochotomy were divided into reflux group and control group. The level of plasma and serum gastrin of the patients and of 12 healthy volunteers were measured by radioimmunoassay. Thirty-four were selected randomly to undergo choledochoscope manometry. Sphincter of Oddi basal pressure (SOBP), amplitude (SOCA), frequency of contractions (SOF), duration of contractions (SOD), duodenal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. RESULTS: Sixteen (35.6%) patients were detected to have duodenal-biliary reflux. SOBP, SOCA and CBDP in the reflux group were much lower than the control group (t=5.254, 3.438 and 3.527, P<0.001). SOD of the reflux group was shorter than the control group (t=2.049, P<0.05). The level of serum gastrin and plasma motilin of the reflux group was much lower than the control group (t= -2.230 and -2.235, P<0.05). There was positive correlation between the level of plasma motilin and SOBP and between the level of serum gastrin and SOBP and CBDP. CONCLUSION: About 35.9% of the patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux. Most of them have sphincter of Oddi hypomotility and the decreased level of plasma motilin and serum gastrin. The disorder of gastrointestinal hormone secretion may result in sphincter of Oddi dysfunction. There is a close relationship between sphincter of Oddi hypomotility and duodenal-biliary reflux.
Assuntos
Bile/metabolismo , Doenças Biliares/complicações , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Refluxo Duodenogástrico/complicações , Gastrinas/sangue , Motilina/sangue , Disfunção do Esfíncter da Ampola Hepatopancreática/etiologia , Esfíncter da Ampola Hepatopancreática/fisiopatologia , Doenças Biliares/etiologia , Doenças Biliares/metabolismo , Doenças Biliares/fisiopatologia , Estudos de Casos e Controles , Colecistectomia/efeitos adversos , Drenagem/efeitos adversos , Refluxo Duodenogástrico/etiologia , Refluxo Duodenogástrico/metabolismo , Refluxo Duodenogástrico/fisiopatologia , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Contração Muscular , Pressão , Radioimunoensaio , Compostos Radiofarmacêuticos/metabolismo , Disfunção do Esfíncter da Ampola Hepatopancreática/metabolismo , Disfunção do Esfíncter da Ampola Hepatopancreática/fisiopatologia , Pentetato de Tecnécio Tc 99m/metabolismoRESUMO
BACKGROUND: The disorders of gallbladder motility may play an important role in the formation of gallstones. Many neural and hormonal factors and their interactions regulate gallbladder motility and bile flow into the duodenum. Further study in these factors may help to reveal the etiology of gallbladder diseases. This study was undertaken to assess the relationship of the levels of motilin, vasoactive intestinal peptide (VIP) and gastrin in blood and gallbladder tissues with the formation of cholelithiasis. METHODS: The levels of motilin, gastrin and VIP in blood and gallbladder tissues of 36 patients with gallbladder stones, 14 patients with gallbladder polyps, 10 healthy volunteers and 10 patients with common bile duct stones were measured by radioimmunoassay. RESULTS: The level of motilin in plasma and gallbladder tissues of the gallbladder stone group was higher than that of the control and gallbladder polyp groups (P<0.05). The levels of plasma VIP and serum gastrin were much higher than those of the other three groups (P<0.01). The level of VIP in gallbladder tissues was higher than that of the control and gallbladder polyp groups (P<0.01). CONCLUSIONS: The abnormal excretion of hormonal factors is closely related to gallstone formation. The high level of VIP in gallbladder tissues may be an important cause of gallbladder hypomotility. The abnormal level of serum gastrin may be related to the gastrointestinal symptoms of patients with gallstones.
Assuntos
Vesícula Biliar/metabolismo , Cálculos Biliares/metabolismo , Hormônios Gastrointestinais/sangue , Hormônios Gastrointestinais/metabolismo , Ducto Colédoco/metabolismo , Feminino , Gastrinas/sangue , Gastrinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Motilina/sangue , Motilina/metabolismo , Pólipos/metabolismo , Peptídeo Intestinal Vasoativo/sangue , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
BACKGROUND: Most reports on the prognosis of cholecystectomy have been short-term studied, and few long-term reports have suggested variable incidences of common bile duct stones after cholecystectomy. We retrospectively reviewed the data to find the possible association between cholecystectomy and the subsequent occurrence of primary common bile duct stones. METHODS: The data were reviewed retrospectively of 478 patients with primary common bile duct stones diagnosed and treated by endoscopic sphincterotomy at our hospitals between January 1994 and December 2003. RESULTS: Sixty-one (14.1%) of the 432 patients had a history of cholecystectomy, with an incidence rate markedly higher than that in the general population. The mean interval between cholecystectomy and the occurrence of primary common bile duct stones was 8.23 years, with the longest being 28 years and the shortest 2 years. Compared with the patients who had not undergone a prior cholecystectomy, those who had had a prior cholecystectomy more often accompanied with acute cholangiolitis (chi(2)=8.259, P<0.01), and multiple stones or sand-like stones were frequently found (chi(2)=9.030, P<0.01). CONCLUSIONS: These results suggest a possible relationship between cholecystectomy and the subsequent occurrence of primary common bile duct stones. Perhaps patients with primary common bile duct stones who have had a prior cholecystectomy have a higher probability of infection of the biliary system. The infection may be one of the causes of occurrence of primary common bile duct stones after cholecystectomy.
Assuntos
Colecistectomia/efeitos adversos , Coledocolitíase/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Disfunção do Esfíncter da Ampola Hepatopancreática/complicaçõesRESUMO
OBJECTIVE: To investigate the relationship between anatomic abnormalities and malfunction of Oddi sphincter with formation of bile duct pigment gallstone. METHODS: One hundred and twenty-three patients with a T tube after cholecystectomy and choledochotomy were divided into reflux group and control group by measuring the amounts of radioactivity of (99m)Tc-DTPA in the bile. Among them 53 were selected randomly to undergo choledochoscopic manometry. Basal pressure of Oddi's sphincter (SOBP), amplitude of Oddi's sphincter (SOCA), frequency of contraction (SOF), duration of contraction (SOD), duodenal pressure (DP), common bile duct pressure (CBDP) were scored and analyzed. The level of plasma motilin and serum gastrin of 45 patients and 12 healthy volunteers were measured by radioimmunoassay. The incidence rates of duodenal descending part diverticulum in patients with bile duct pigment stones, patients without alimentary tract diseases, patients with gallbladder polyps, patients with gallbladder stones were studied by means of barium meal examination. The incidence rates of intraduodenal peri-ampullary diverticulum in patients with primary bile duct pigment stones, patients with bile duct stone and gallbladder stones, patients with bile duct stones originating from the gallbladder, patients with inflammation and stricture of the extremity of bile duct and papilla, patients with cancer of the extremity of bile duct and papilla, patients with post-cholecystectomy syndrome were detected by duodenoscope. RESULTS: Of the patients, 44 were detected with duodenal-biliary reflux (35.8%). SOBP, SOCA and CBDP in the reflux group were much lower than those in control group (P < 0.001). The level of serum gastrin and plasma motilin of the reflux group were much lower than those of control group (P < 0.01). Positive correlation was found between level of motilin and SOBP while level of gastrin was positively correlated with SOBP and CBDP. The incidence of duodenal diverticulum in patients with bile duct pigment stone was 36.62%, which was higher than that of the other 3 groups. The incidence rate of intraduodenal peri-ampullary diverticulum in patients with primary bile duct pigment stone was higher than that of patients with inflammation and stricture of the extremity of bile duct and papilla, patients with cancer of the extremity of bile duct and papilla and patients with bile duct stones originating from the gallbladder. CONCLUSIONS: The patients with bile duct pigment stone have apparent duodenal-biliary reflux and infection of the bile duct. The state of structure and function of Oddi's sphincter is correlated significantly with bile duct pigment stone. The anatomic abnormalities and malfunction of Oddi's sphincter played an important role in the formation of bile duct pigment stone.