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1.
Asia Pac J Clin Oncol ; 18(2): e157-e162, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34314570

RESUMO

BACKGROUND: B10 cells, a subset of regulatory B cells, can inhibit antitumor response and thus promote tumor development. This study explored the clinical meaning and prognostic value of circulating B10 cells in colorectal cancer (CRC). MATERIALS AND METHODS: The proportion of B10 cells in peripheral blood in CRC patients and healthy controls was detected by multicolor flow cytometry. RESULTS: The proportion of circulating B10 cells was remarkably elevated in CRC patients compared to normal controls (% of CD19+ B cells; 16.6% (IQR 6.0%) versus 9.0% (IQR 5.7%), p < 0.001). B10 cells proportion was associated with tumor size, depth of invasion, lymph node metastasis, and TNM stage in CRC. Kaplan-Meier analysis indicated that CRC patients with high B10 cells proportion suffered worse overall survival than those with low B10 cells proportion. Multivariate analysis revealed that the proportion of B10 cells was an independent prognostic indicator for CRC patients. CONCLUSION: Our results indicate that the proportion of circulating B10 cells is an independent prognostic factor for patients with CRC and thus may help guide the clinical decision in CRC.


Assuntos
Neoplasias Colorretais , Biomarcadores Tumorais , Neoplasias Colorretais/patologia , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico
2.
Exp Ther Med ; 22(6): 1473, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34737813

RESUMO

Tea polyphenols (TPs) are the major bioactive extract from green tea that have been extensively reported to prevent and treat oxidative stress damage. In previous studies, TPs have been demonstrated to protect cells against oxidative injury induced by hydrogen peroxide (H2O2). However, the underlying mechanism remains unclear. The aim of the current study was to investigate whether the protective and regulatory effects of TPs on oxidative stress damage were dependent on the mammalian STE20-like protein kinase (Mst)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2) axis and the Kelch-like ECH-associated protein 1 (Keap1)/Nrf2/heme oxygenase 1 (HO-1) pathway in RAW264.7 cells, a murine macrophage cell line. Maintaining a certain range of intracellular reactive oxygen species (ROS) levels is critical to basic cellular activities, while excessive ROS generation can override the antioxidant capacity of the cell and result in oxidative stress damage. The inhibition of ROS generation offers an effective target for preventing oxidative damage. The results of the present study revealed that pretreatment with TPs inhibited the production of intracellular ROS and protected RAW264.7 cells from H2O2-induced oxidative damage. TPs was also demonstrated to attenuate the production of nitric oxide and malondialdehyde and increase the levels of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase). In addition, following TPs treatment, alterations in Mst1/2 at the mRNA and protein level inhibited the production of ROS and promoted the self-regulation of antioxidation. TPs-induced Keap1 gene downregulation also increased the expression of Nrf2 and HO-1. Collectively, the results of the present study demonstrated that TPs provided protection against H2O2-induced oxidative injury in RAW264.7 cells.

3.
Front Oncol ; 10: 547011, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072575

RESUMO

BACKGROUND: Dual-specificity phosphatase 9 (DUSP9) belongs to the dual-specificity protein phosphatase subfamily. Recently, increasing attention has been paid on the role of DUSP9 in a variety of cancers. However, its functional role in tumor development is still unclear, especially in colorectal cancer (CRC). METHODS: The functional role of DUSP9 in inhibiting the progression of CRC was verified using colony formation assay, wound healing assay, nude mice xenograft model, etc. RNA-seq was performed to assess the gene expression profiling in SW480 cells with DUSP9 stable knockdown and shControl cells. Bisulfite sequencing (BSE) was performed to reveal the methylation status of CpG island in the promoter of DUSP9. RESULTS: DUSP9 was significantly downregulated in tumor tissues compared with peritumor tissues. Mechanistically, the high methylation status of CpG island in the promoter of DUSP9 may lead to the downregulation of DUSP9 in CRC. Clinically, low DUSP9 expression in CRC was closely associated with depth of invasion, metastasis (TNM) stage, and poor survival, indicating that DUSP9 may be involved in the progression of CRC. Functional study revealed that DUSP9 inhibited proliferation, migration, invasion, and epithelial-mesenchymal transition of CRC cells both in vitro and in vivo. Transcriptome profiling studies revealed that Erk signaling was involved in the tumor progression mediated by DUSP9 silencing, which is confirmed by cell experiments and clinical tissue sample staining analysis. CONCLUSION: Our findings demonstrate that DUSP9 plays a critical role in the progression of CRC, and therapeutic intervention to increase the expression or activity of DUSP9 may be a potential target for CRC treatment in the future.

4.
World J Gastrointest Oncol ; 12(7): 782-790, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32864045

RESUMO

BACKGROUND: Gastric cancer is the second most common malignant tumor in China, ranking third among all malignant tumor mortality rates. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to increase significantly the effectiveness of intraperitoneal chemotherapeutic drugs, prolong the action time of these drugs on intraperitoneal tumor cells, and enhance their diffusion in tumor tissues. HIPEC may be one of the best choices for the eradication of residual cancer cells in the abdominal cavity. AIM: The aim of this study was to study the role of preventive HIPEC after radical gastrectomy. METHODS: A prospective analysis was performed with patients with cT4N0-3M0 gastric cancer to compare the effects of postoperative prophylactic HIPEC plus intravenous chemotherapy with those of routine adjuvant chemotherapy. Patients' medical records were analyzed, and differences in the peritoneal recurrence rate, disease-free survival time, and total survival time between groups were examined. RESULTS: The first site of tumor recurrence was the peritoneum in 11 cases in the conventional adjuvant chemotherapy group and in 2 cases in the HIPEC group (P = 0.020). The 1-year and 3-year disease-free survival rates were 91.9% and 60.4%, respectively, in the conventional adjuvant chemotherapy group and 92.1% and 63.0%, respectively, in the HIPEC group. The 1-year and 3-year overall survival rates were 95.2% and 66.3%, respectively, in the conventional adjuvant chemotherapy group and 96.1% and 68.6%, respectively, in the HIPEC group. No significant difference in postoperative or chemotherapy complications was observed between groups. CONCLUSION: In patients with cT4N0-3M0 gastric cancer, prophylactic HIPEC after radical tumor surgery is beneficial to reduce peritoneal tumor recurrence and prolong survival.

5.
Cell Death Dis ; 11(5): 313, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366840

RESUMO

Primary liver cancer (PLC) may be mainly classified as the following four types: hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), hepatoblastoma (HB), and combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (cHCC-ICC). The majority of PLC develops in the background of tumor microenvironment, such as inflammatory microenvironments caused by viral hepatitis, alcoholic or nonalcoholic steatohepatitis, carbon tetrachloride (CCl4), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and necroptosis-associated hepatic cytokine microenvironment caused by necroptosis of hepatocytes. However, the impact of different types of microenvironments on the phenotypes of PLC generated by distinct oncogenes is still unclear. In addition, the cell origin of different liver cancers have not been clarified, as far as we know. Recent researches show that mature hepatocytes retain phenotypic plasticity to differentiate into cholangiocytes. More importantly, our results initially demonstrated that HCC, ICC, and cHCC-ICC could originate from mature hepatocytes rather than liver progenitor cells (LPCs), hepatic stellate cells (HSCs) and cholangiocytes in AKT-driven, AKT/NICD-driven and AKT/CAT-driven mouse PLC models respectively by using hydrodynamic transfection methodology. Therefore, liver tumors originated from mature hepatocytes embody a wide spectrum of phenotypes from HCC to CC, possibly including cHCC-ICC and HB. However, the underlying mechanism determining the cancer phenotype of liver tumors has yet to be delineated. In this review, we will provide a summary of the possible mechanisms for directing the cancer phenotype of liver tumors (i.e., ICC, HCC, and cHCC-ICC) in terms of oncogenic driver genes and tumor microenvironment. Moreover, this study initially revealed the cell origin of different types of liver cancer.


Assuntos
Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Oncogenes , Microambiente Tumoral/genética , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Hepatócitos/patologia , Humanos , Transdução de Sinais/genética
6.
Oncogene ; 39(17): 3522-3540, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32111984

RESUMO

Metastasis is a major cause of high recurrence and poor survival of patients with colorectal cancer (CRC), although the mechanisms associated with this process remain poorly understood. In this study, we report a novel mechanism by which SOX13 promotes CRC metastasis by transactivating SNAI2 and c-MET. SOX13 overexpression was significantly correlated with more aggressive clinicopathological features of CRC and indicated poor prognosis in two independent cohorts of CRC patients (cohort I, n = 363; cohort II, n = 390). Overexpression of SOX13-promoted CRC migration, invasion, and metastasis, whereas SOX13 downregulation caused the opposite effects. Further mechanistic investigation identified SNAI2 and MET as important target genes of SOX13 using serial deletion and site-directed mutagenesis luciferase reporter and chromatin immunoprecipitation (ChIP) assays, as well as functional complementation analyses. In addition, SOX13 was shown to be a direct target of HGF/STAT3 signaling, and the c-MET inhibitor crizotinib blocked the HGF/STAT3/SOX13/c-MET axis, significantly inhibiting SOX13-mediated CRC migration, invasion and metastasis. Moreover, in clinical CRC tissues, SOX13 expression was positively correlated with the expression of SNAI2, c-MET, and HGF. CRC patients with positive coexpression of SOX13/SNAI2, SOX13/c-MET, or HGF/SOX13 exhibited a worse prognosis. In summary, SOX13 is a promising prognostic biomarker in patients with CRC, and blocking the HGF/STAT3/SOX13/c-MET axis with crizotinib could be a new therapeutic strategy to prevent SOX13-mediated CRC metastasis.


Assuntos
Autoantígenos/metabolismo , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-met/biossíntese , Fatores de Transcrição SOXD/metabolismo , Fatores de Transcrição da Família Snail/biossíntese , Ativação Transcricional , Animais , Autoantígenos/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-met/genética , Fatores de Transcrição SOXD/genética , Fatores de Transcrição da Família Snail/genética
7.
Theranostics ; 9(13): 3879-3902, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281520

RESUMO

Background: Metastasis is the major reason for high recurrence rates and poor survival among patients with colorectal cancer (CRC). However, the underlying molecular mechanism of CRC metastasis is unclear. This study aimed to investigate the role of forkhead box K2 (FOXK2), one of the most markedly increased FOX genes in CRC, and the mechanism by which it is deregulated in CRC metastasis. Methods: FOXK2 levels were analyzed in two independent human CRC cohorts (cohort I, n = 363; cohort II, n = 390). In vitro Transwell assays and in vivo lung and liver metastasis models were used to examine CRC cell migration, invasion and metastasis. Chromatin immunoprecipitation and luciferase reporter assays were used to measure the binding of transcription factors to the promoters of FOXK2, zinc finger E-box binding homeobox 1 (ZEB1) and epidermal growth factor receptor (EGFR). Cetuximab was utilized to treat FOXK2-mediated metastatic CRC. Results: FOXK2 was significantly upregulated in human CRC tissues, was correlated with more aggressive features and indicated a poor prognosis. FOXK2 overexpression promoted CRC migration, invasion and metastasis, while FOXK2 downregulation had the opposite effects. ZEB1 and EGFR were determined to be direct transcriptional targets of FOXK2 and were essential for FOXK2-mediated CRC metastasis. Moreover, activation of EGFR signaling by EGF enhanced FOXK2 expression via the extracellular regulated protein kinase (ERK) and nuclear factor (NF)-κB pathways. The EGFR monoclonal antibody cetuximab significantly inhibited FOXK2-promoted CRC metastasis. In clinical CRC tissues, FOXK2 expression was positively correlated with the expression of p65, ZEB1 and EGFR. CRC patients who coexpressed p65/FOXK2, FOXK2/ZEB1 and FOXK2/EGFR had poorer prognosis. Conclusions: FOXK2 serves as a prognostic biomarker in CRC. Cetuximab can block the EGF-NF-κB-FOXK2-EGFR feedback loop and suppress CRC metastasis.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Regulação para Cima/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Idoso , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Cetuximab/farmacologia , Cetuximab/uso terapêutico , Estudos de Coortes , Neoplasias Colorretais/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Análise Multivariada , NF-kappa B/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Prognóstico , Análise de Sobrevida , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/genética , Regulação para Cima/efeitos dos fármacos , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
8.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(2): 143-148, 2019 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-30799536

RESUMO

OBJECTIVE: To compare the prognostic value of TNM staging systems in the 7th edition and the 8th edition AJCC in Siewert III adenocarcinoma of esophagogastric junction (AEG). METHODS: Data of 160 patients with Siewert III AEG who underwent radical surgery (R0) from January 2009 to January 2013 in PLA General Hospital were collected retrospectively. Exclusion standards:(1)preoperative neoadjuvant chemoradiotherapy;(2)with distant metastasis before or during operation;(3)palliative operation or R1/R2 resection;(4)pathological type as non-adenocarcinoma;(5)number of retrieved lymph nodes less than 16;(6)diagnosed with other malignant tumors concurrently or within 5 years after operation;(7)incomplete clinical or follow-up data. According to the above criteria, 160 patients were included in this study finally. All the patients underwent radical total or proximal gastrectomy by abdominal approach. D1 or D1+ lymph node dissection was performed in early patients and D2 in advanced patients. All the patients were re-staged by the gastric cancer TNM7 (G7), the gastric cancer TNM8 (G8) and the esophageal cancer TNM7(E7). Univariate analysis and Cox regression analysis were performed. Kappa value and Akaike's information criterion (AIC, the less AIC, the better prognosis) value were compared between different staging systems in agreement and predicting prognosis. RESULTS: There were 128 males and 32 females(sex ratio 4:1), and the average age was (60.2±11.6) years and 17 patients with basic disease. Of all the patients, 133 cases (83.1%) underwent radical total gastrectomy and 27 cases (16.9%) underwent proximal gastrectomy. The median number of dissected lymph nodes were 31 and the median number of positive lymph nodes were 4. Multivariate analysis showed that the G7, G8, E7 staging systems were independent prognostic factors (HR=1.374, 1.407 and 1.305 respectively,all P<0.001). Stage migration between G7 and G8 were only observed in IIIA, IIIB and IIIC, and stage migration rate was 8.1% (13/160), and the agreement was very good (weighted Kappa 0.904, P<0.001). However, the difference between G8 and E7 was quite obvious, stage migration rate was 40.6%(65/160), and the agreement between G8 and E7 was not satisfied (weighted Kappa 0.536, P<0.001). AIC value was 811.4 in G8, 812.8 in G7 and 815.9 in E7, respectively. CONCLUSION: Compared with G7 and E7 staging systems, the G8 staging system is superior in predicting the prognosis of patients with Siewert III AEG.


Assuntos
Adenocarcinoma/patologia , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Estadiamento de Neoplasias/métodos , Neoplasias Gástricas/patologia , Adenocarcinoma/classificação , Adenocarcinoma/cirurgia , Idoso , Neoplasias Esofágicas/classificação , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/cirurgia , Feminino , Gastrectomia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/classificação , Neoplasias Gástricas/cirurgia
9.
Oncotarget ; 9(63): 32250-32261, 2018 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-30181814

RESUMO

The associations between fruit and vegetable consumption and pancreatic cancer risk are inconclusive. We conducted a meta-analysis of prospective studies to investigate the associations. The search was conducted systemically using the PubMed and EMBASE databases up to March 2017. Relative risks and 95% confidence intervals for the highest versus lowest consumption and dose-response analyses were assessed. Subtype and subgroup analyses were performed. Twelve studies were eligible. The summary relative risks of the highest versus lowest consumption were 0.95 (0.80-1.12) for total fruits and vegetables without heterogeneity (I2 = 0%, P = 0.44), 0.96 (0.82-1.12) for fruits without low heterogeneity (I2 = 37%, P = 0.12) and 0.94 (0.84-1.06) for vegetables with low heterogeneity (I2 = 9%, P= 0.36). Dose-response analyses also showed no significantly inverse associations for each 100 g/day increase; the summary relative risks were 1.00 (0.98-1.02) for total fruits and vegetables, 1.01 (0.97-1.05) for fruits and 1.00 (0.97-1.03) for vegetables. The results of subtype analyses were consistent with the fruit and vegetable analyses; the relative risks were 0.97 (0.80-1.17) for citrus fruit without low heterogeneity (I2 = 39%, P = 0.15) and 0.89 (0.76-1.05) for cruciferous vegetables without low heterogeneity (I2 = 14%, P= 0.32). In conclusion, this meta-analysis does not support significant associations between fruit and vegetable consumption and pancreatic cancer risk.

10.
FEBS Open Bio ; 8(2): 189-200, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29435409

RESUMO

Fewer than 30% of patients with hepatocellular carcinoma (HCC) are eligible to receive curative therapies, and so a better understanding of the molecular mechanisms of HCC is needed to identify potential therapeutic targets. The role of microRNA (miRNA) in modulating tumour progression has been demonstrated, and therapies targeting miRNA appear promising. miR-204-5p has been shown to function in numerous types of cancer, but its role in HCC remains unclear. In this study, we found that miR-204-5p expression was downregulated in cancerous HCC tissues compared to nontumour tissues. Kaplan-Meier survival curve analysis also showed that low expression of miR-204-5p predicted worse outcomes of HCC patients. In addition, miR-204-5p expression was significantly lower in HCC cell lines. The function of miR-204-5p was also assessed both in vitro and in vivo. We demonstrated that ectopic expression of miR-204-5p in HCC cell lines inhibited HCC cell proliferation and clonogenicity using CCK8, BrdU and colony-forming assays, while the inhibition of miR-204-5p enhanced proliferation and clonogenicity. Further in vivo studies in mice further confirmed the proliferation capacity of miR-204-5p. We also identified sine oculis homeobox homologue 1 (SIX1) as a direct target of miR-204-5p and showed that it was inversely correlated with miR-204-5p in both human and mouse HCC tissues. Transfection of miR-204-5p mimics in BEL-7404 cells blocked the cell cycle by inhibiting the expression of cyclin-D1 and cyclin-A1, cell cycle-related factors regulated by SIX1. More importantly, overexpression of the 3'UTR mutant SIX1 but not the wild-type SIX1 abolished the suppressive effect of miR-204-5p, and downregulated SIX1 in BEL-7402 cells that transfected with miR-204 inhibitors could partly block the inhibitory effect of miR-204-5p on proliferation. Thus, we have demonstrated that miR-204-5p suppresses HCC proliferation by directly regulating SIX1 and its downstream factors.

11.
Oncotarget ; 8(34): 56428-56442, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28915602

RESUMO

Calponin 2 plays an important role in regulating actin cytoskeleton, which is critical for cell division and migration. Previous studies have demonstrated that calponin 2 inhibits prostate cancer cell proliferation and metastasis. However, the role of calponin 2 in pancreatic tumor growth, metastasis and patient survival remains unclear. Here, we demonstrate that the level of calponin 2 is a positive prognostic factor for patients with pancreatic ductal adenocarcinoma (PDAC). Patients with high calponin 2 expression in the tumor presented less lymph node metastasis and longer survival. Knockdown of calponin 2 facilitated pancreatic cancer cell proliferation and metastasis. Further experiments suggested that PI3K/AKT, NF-κB, Vimentin, Fibronectin, Snail and Slug were upregulated and E-cadherin was downregulated after calponin 2 was knocked down, implicating altered functions in PDAC proliferation and metastasis. In addition, we verified that calponin 2 functioned through inhibiting PI3K/AKT and NF-κB pathways. Our study suggests that the upregulation of calponin 2 in PDAC correlates to lower malignancy and presents a novel target for the development of new treatment.

12.
J Clin Gastroenterol ; 51(7): 586-593, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28682990

RESUMO

BACKGROUND: Hypertriglyceridemia has been positively associated with the risk of acute pancreatitis (AP), but whether increased triglyceride (TG) levels are associated with the severity of AP remains unknown. To this, a meta-analysis was conducted to assess the effect of elevated serum TG on the prognosis of AP. METHODS: We searched PubMed, EMBASE, and the Cochrane library to identify all eligible studies (up to September 2016). We pooled the odds ratios (ORs) or standardized mean difference from individual studies using a random-effects model to investigate associations between levels of TG and the prognosis of AP. RESULTS: A total of 15 studies were included in the meta-analysis, including a total of 1564 patients with triglyceride-related acute pancreatitis (TGAP) and 5721 patients with nontriglyceride-related acute pancreatitis (NTGAP). The occurrence of renal failure [OR=3.18; 95% confidence interval (CI): 1.92, 5.27; P<0.00001], respiratory failure (OR=2.88; 95% CI: 1.61, 5.13; P<0.0001), and shock (OR=3.78; 95% CI: 1.69, 8.44; P<0.0001) was statistically significantly higher in TGAP group than in NTGAP group. Furthermore, mortality (OR=1.90; 95% CI: 1.05, 3.45; P<0.01), systemic inflammatory response syndrome (OR=2.03; 95% CI: 1.49, 2.75; P<0.00001), and Acute Physiology and Chronic Health Evaluation (APACHE-II) scores (standardized mean difference=2.72; 95% CI: 1.00, 4.45; P<0.001) were also statistically significantly higher in TGAP group than in NTGAP group. CONCLUSION: Elevated serum TGs are related to a worse prognosis of AP.


Assuntos
Hipertrigliceridemia/complicações , Pancreatite/diagnóstico , Triglicerídeos/sangue , Doença Aguda , Biomarcadores/sangue , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/diagnóstico , Modelos Estatísticos , Estudos Observacionais como Assunto , Razão de Chances , Pancreatite/sangue , Pancreatite/etiologia , Prognóstico , Índice de Gravidade de Doença
13.
Sci Rep ; 7(1): 734, 2017 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-28389636

RESUMO

Fatty liver (FL) is one of the risk factors for acute pancreatitis and is also indicative of a worse prognosis as compared to acute pancreatitis without fatty liver (AP). The aim of the present study was to analyze, at the hepatic level, the differentially expressed genes (DEGs) between acute pancreatitis with fatty liver (APFL) rats and AP rats. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses of these DEGs indicated that PPARα signalling pathway and fatty acid degradation pathway may be involved in the pathological process of APFL, which indicated that fatty liver may aggravate pancreatitis through these pathways. Moreover, the excessive activation of JAK/STAT signaling pathway and toll-like receptor signaling pathway was also found in APFL group as shown in heat map. In conclusion, the inhibition of PPARα signaling pathway and the fatty acid degradation pathway may lead to the further disorder of lipid metabolism, which can aggravate pancreatitis.


Assuntos
Fígado Gorduroso/complicações , Pancreatite/complicações , Pancreatite/genética , Análise de Sequência de RNA , Transcriptoma , Doença Aguda , Animais , Biópsia , Biologia Computacional , Dieta , Ácidos Graxos/metabolismo , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Redes e Vias Metabólicas , PPAR alfa/metabolismo , Pancreatite/metabolismo , Pancreatite/patologia , Ratos , Reprodutibilidade dos Testes , Transdução de Sinais
14.
Pancreatology ; 16(6): 952-957, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27654573

RESUMO

BACKGROUND: To investigate the accuracy of resistin, leptin and adiponectin levels in predicting persistent organ failure in patients with acute pancreatitis (AP). METHODS: Data from 90 consecutive patients admitted to our hospital for AP were retrospectively collected from an ongoing prospective cohort study. The levels of adiponectin, leptin and resistin were measured and compared between patients with and without persistent organ failure. The accuracy of the adipokines in predicting persistent organ failure were compared with the patients' Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, and were separately investigated in overweight and non-overweight groups. RESULTS: Persistent organ failure occurred in 26.7% of the patients. The levels of resistin were significantly increased in AP patients with persistent organ failure, in both the overweight and the non-overweight subgroups. Resistin and APACHE-II score predicted persistent organ failure with comparable areas under the curve (AUC) of 0.72 and 0.75, respectively (p = 0.66). Resistin demonstrated similar accuracy with the APACHE-II score in predicting persistent organ failure in the overweight (0.69 vs. 0.66, p = 0.82) and non-overweight (0.76 vs. 0.87, p = 0.39) subgroups. There was no correlation between adiponectin and persistent organ failure, but a weak correlation between leptin and persistent organ failure was demonstrated. CONCLUSIONS: Resistin and leptin levels, rather than adiponectin, correlate with persistent organ failure in patients with AP.


Assuntos
Leptina/sangue , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia , Pancreatite/complicações , Resistina/sangue , APACHE , Doença Aguda , Adipocinas/sangue , Adiponectina/sangue , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/sangue , Sobrepeso/sangue , Sobrepeso/complicações , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do Tratamento
15.
Oncotarget ; 7(38): 61390-61402, 2016 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-27542217

RESUMO

O-GlcNAc transferase (OGT) is the only enzyme in mammals that catalyzes the attachment of ß-D-N-acetylglucosamine (GlcNAc) to serine or threonine residues of target proteins. Hyper-O-GlcNAcylation is becoming increasingly realized as a general feature of cancer and contributes to rapid proliferation of cancer cells. In this study, we demonstrated that O-GlcNAc and OGT levels were increased in all six gastric cancer (GC) cell lines as compared with immortal gastric epithelial cells. Downregulation of the O-GlcNAcylation level by silencing OGT inhibited cell viability and growth rate via the cdk-2, cyclin D1 and ERK 1/2 pathways. In vivo xenograft assays also demonstrated that the hyper-O-GlcNAc level markedly promoted the proliferation of tumors. Moreover, compared with noncancerous tissues, the O-GlcNAcylation level was increased in cancerous tissues. GC patients with higher levels of O-GlcNAcylation exhibited large tumor sizes (≥5 cm), deep tumor invasion (T3 and T4), high AJCC stages (stage III and IV), more lymph node metastases and lower overall survival. Notably, the phosphorylation level of ERK 1/2 was increased progressively with the increase of O-GlcNAcylation in both SGC 7901 and AGS cells. Consistently, human GC tissue arrays also revealed that ERK 1/2 signaling was positively correlated to O-GlcNAcylation (r = 0.348; P = 0.015). Taken together, here we reported that hyper-O-GlcNAcylation significantly promotes GC cells proliferation by modulating cell cycle related proteins and ERK 1/2 signaling, suggesting that inhibition of OGT may be a potential novel therapeutic target of GC.


Assuntos
Acetilglucosamina/metabolismo , Ciclina D1/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Sistema de Sinalização das MAP Quinases , N-Acetilglucosaminiltransferases/metabolismo , Processamento de Proteína Pós-Traducional , Neoplasias Gástricas/patologia , Animais , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , N-Acetilglucosaminiltransferases/genética , Fosforilação , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Serina/metabolismo , Treonina/metabolismo , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Inflamm Res ; 65(8): 647-54, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27085321

RESUMO

BACKGROUND: B10 cells are specific B cell subsets with the capacity of producing IL-10 to inhibit immune responses. Several studies have demonstrated that B10 cells are correlated with some immune and inflammatory diseases, such as experimental autoimmune encephalomyelitis (EAE), collagen-induced arthritis (CA), colitis and contact hypersensitivity. However, its role in severe acute pancreatitis (SAP) has not been clearly demonstrated yet. PURPOSE: In this study, we show that B10 cells can inhibit inflammation of severe acute pancreatitis (SAP). MATERIALS AND METHODS: Blood from 17 patients with SAP and 22 age-matched healthy volunteers were collected to detect the proportion of B10 cells. CD19-/- mice were used as B10 cell-deficient mice. Amylase and lipase levels, pancreatic edema and HE staining were tested to assess the severity of SAP. RESULTS: CD19-/- mice, which lack B10 cells, suffered a more severe inflammation in pancreas compared with wild-type mice after caerulein injection. The frequency of B10 cells was decreased both in SAP patients and SAP animal models. Adoptive transfer of B10 cells ameliorates inflammatory injury of pancreatitis in CD19-/- mice. CONCLUSION: Thus, we identified B10 cells as a protective factor for SAP and provided a novel target for SAP treatment.


Assuntos
Subpopulações de Linfócitos B/imunologia , Pancreatite/imunologia , Adolescente , Transferência Adotiva , Adulto , Idoso , Animais , Antígenos CD19/genética , Ceruletídeo , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Pâncreas/patologia , Pancreatite/induzido quimicamente , Pancreatite/patologia , Baço/citologia , Baço/imunologia , Adulto Jovem
17.
J Gastroenterol Hepatol ; 31(9): 1539-45, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26860924

RESUMO

BACKGROUND AND AIM: Chromoendoscopy (CE) is widely used in the diagnosis of early gastric cancer (EGC) and premalignant gastric lesions (PGLs). We conducted a meta-analysis to evaluate the diagnostic efficacy of CE for EGC and PGLs. METHODS: We searched PubMed/MEDLINE, EMBASE, and the Cochrane library to identify all eligible studies according to inclusion and exclusion standards. Publication bias was tested using Funnel plots and Egger's test. The possible sources of the heterogeneity were explored by performing a meta-regression analysis. Heterogeneity was assessed by the Q test and I(2) statistic. RESULTS: Ten studies met the inclusion standards, including a total of 699 patients and 902 lesions. The pooled sensitivity, specificity, and area under the curve of CE were 0.90 (95% confidence interval, 0.87-0.92), 0.82 (95% confidence interval, 0.79-0.86), and 0.9464, respectively. In subgroup analysis of diagnostic accuracy, CE showed higher accuracy versus standard white light endoscopy for EGC (P = 0.005) and PGLs (P = 0.001). CONCLUSION: Chromoendoscopy seems to have a high diagnostic efficacy and improve the detection of EGC and PGLs compared with standard white light endoscopy.


Assuntos
Detecção Precoce de Câncer/métodos , Gastroscopia/métodos , Lesões Pré-Cancerosas/diagnóstico , Neoplasias Gástricas/diagnóstico , Corantes , Humanos
18.
Sci Rep ; 5: 8626, 2015 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-25733152

RESUMO

MG7-Ag, a specific gastric cancer-associated antigen, can be used to non-invasively monitor gastric cancer by molecular imaging with positron emission tomography/computed tomography (PET/CT). In this study, we prepared and evaluated a (68)Ga-labeled MG7 antibody as a molecular probe for nanoPET/CT imaging of gastric cancer in a BGC-823 tumor xenografted mouse model. Macrocyclic chelator 1,4,7-triazacyclononane-N,N0,N00-triacetic acid (NOTA)-conjugated MG7 antibody was synthesized and radiolabeled with (68)Ga (t1/2 = 67.71 min). Then, (68)Ga-NOTA-MG7 was tested using in vitro cytological studies, in vivo nanoPET/CT and Cerenkov imaging studies as well as ex vivo biodistribution and histology studies. The in vitro experiments demonstrated that (68)Ga-NOTA-MG7 has an excellent radiolabeling efficiency of approximately 99% without purification, and it is stable in serum after 120 min of incubation. Cell uptake and retention studies confirmed that (68)Ga-NOTA-MG7 has good binding affinity and tumor cell retention. For the nanoPET imaging study, the predominant uptake of (68)Ga-NOTA-MG7 was visualized in tumor, liver and kidneys. The tumor uptake reached at its peak (2.53 ± 0.28%ID/g) at 60 min pi. Cherenkov imaging also confirmed the specificity of tumor uptake. Moreover, the biodistribution results were consistent with the quantification data of nanoPET/CT imaging. Histologic analysis also demonstrated specific staining of BGC-823 tumor cell lines.


Assuntos
Anticorpos Monoclonais , Antígenos de Neoplasias/imunologia , Radioisótopos de Gálio , Tomografia por Emissão de Pósitrons , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/imunologia , Tomografia Computadorizada por Raios X , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Xenoenxertos , Humanos , Camundongos , Microscopia Confocal , Distribuição Tecidual
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