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1.
J Clin Transl Hepatol ; 11(6): 1341-1354, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37719959

RESUMO

Background and Aims: Liver ischemia-reperfusion (IR) injury is a common pathological process in liver surgery. Ferroptosis, which is closely related to lipid peroxidation, has recently been confirmed to be involved in the pathogenesis of IR injury. However, the development of drugs that regulate ferroptosis has been slow, and a complete understanding of the mechanisms underlying ferroptosis has not yet been achieved. Fucoidan (Fu) is a sulfated polysaccharide that has attracted research interest due to its advantages of easy access and wide biological activity. Methods: In this study, we established models of IR injury using erastin as an activator of ferroptosis, with the ferroptosis inhibitor ferrostatin-1 (Fer-1) as the control. We clarified the molecular mechanism of fucoidan in IR-induced ferroptosis by determining lipid peroxidation levels, mitochondrial morphology, and key pathways in theta were involved. Results: Ferroptosis was closely related to IR-induced hepatocyte injury. The use of fucoidan or Fer-1 inhibited ferroptosis by eliminating reactive oxygen species and inhibiting lipid peroxidation and iron accumulation, while those effects were reversed after treatment with erastin. Iron accumulation, mitochondrial membrane rupture, and active oxygen generation related to ferroptosis also inhibited the entry of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus and reduced downstream heme oxygenase-1 (HO-1) and glutathione peroxidase 4 (GPX4) protein levels. However, fucoidan pretreatment produced adaptive changes that reduced irreversible cell damage induced by IR or erastin. Conclusions: Fucoidan inhibited ferroptosis in liver IR injury via the Nrf2/HO-1/GPX4 axis.

2.
Exp Ther Med ; 24(1): 463, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35747148

RESUMO

[This corrects the article DOI: 10.3892/etm.2021.10865.].

3.
Exp Ther Med ; 22(6): 1430, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34707711

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a complex type of liver disease that represents an important global health threat. The mechanistic basis of this disease remains incompletely understood. The present study sought to explore whether microRNA (miR)-506-3p served a functional role in the onset and/or progression of NAFLD. To that end, high levels of glucose were used to treat liver cancer cell lines (HepG2 and Huh7) to model hepatic steatosis, and the expression levels of miR-506-3p and its downstream target genes were assessed. The cells of this hepatic steatosis model were transfected with miR-506-3p mimic molecules to explore the effect of miR-506-3p overexpression on cell viability, target gene expression and AMP-activated protein kinase (AMPK) phosphorylation. Via bioinformatics approaches, sirtuin 1 (SIRT1) was identified as a potential miR-506-3p target gene with relevance in NAFLD, and this interaction was confirmed via luciferase reporter assay. In the hepatic steatosis model of the present study, miR-506-3p expression level was significantly increased, whereas SIRT1 mRNA/protein levels and AMPK phosphorylation levels were markedly decreased. Transfection of the cells with miR-506-3p mimics led to significant SIRT1 downregulation, while miR-506-3p inhibitor molecules exhibited the opposite effect, with similar trends observed in the phosphorylation status of AMPK. These results suggested that miR-506-3p can inhibit SIRT1 expression and associated AMPK phosphorylation in HepG2 and Huh7 cells in an in vitro hepatic steatosis model system. These data indicated that the miR-506-3p/SIRT1/AMPK axis may be valuable as a therapeutic target in patients affected by NAFLD.

4.
Cell Cycle ; 20(23): 2507-2518, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34658294

RESUMO

N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. There is extensive evidence indicating that long non-coding RNAs (lncRNAs) serve as key regulators of oncogenesis and tumor progression in humans. Through prior study has assessed that LIFR-AS1 plays a key role in various kinds of malignant tumors. However, the exact role of m6A induced LIFR-AS1 in pancreatic cancer (PC) and its potential molecular mechanisms remain largely unknown. In this study, we determined that PC cell lines and tumors exhibit increased LIFR-AS1 expression that correlates with larger tumor size, lymph node metastasis, and more advanced TNM stage. Functionally, loss-of-function studies indicated that LIFR-AS1 knockdown decreased the proliferation, migration, and invasion of PC cells in vitro. Mechanistically, we found that METTL3 induced m6A hyper-methylation on the 3' UTR of LIFR-AS1 to enhance its mRNA stability and LIFR-AS1 could directly interact with miR-150-5p, thereby indirectly up-regulating VEGFA expressions within cells. Through rescue experiments, we were able to confirm that the unfavorable impact of LIFR-AS1 knockdown on VEGFA /PI3K/Akt Signaling could be reversed via the inhibition of miR-150-5p expression. Together, these findings indicate that a noval m6A-LIFR-AS1 axis promotes PC progression at least in part via regulation of the miR-150-5p/VEGFA axis, indicating that this regulatory axis may be a viable clinical target for the treatment of PC.


Assuntos
Adenosina/análogos & derivados , Subunidade alfa de Receptor de Fator Inibidor de Leucemia , Metiltransferases , MicroRNAs , Neoplasias Pancreáticas , RNA Longo não Codificante , Fator A de Crescimento do Endotélio Vascular , Adenosina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/genética , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Regulação para Cima/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Bioengineered ; 12(1): 5241-5252, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34402722

RESUMO

Colon adenocarcinoma (COAD) is one of the most common types of malignancy and accounts for >3 million deaths worldwide each year. The present study aimed to evaluate the role of notum palmitoleoyl-protein carboxylesterase (NOTUM) in in vivo and in vitro, and to identify the relationship between NOTUM and the apoptosis of COAD. Moreover, the present study aimed to investigate whether NOTUM regulated Fas cell surface death receptor (FAS)-mediated apoptosis was affected by the Wnt signaling pathway. Gene expression profiling interactive analysis (GEPIA) was used to predict the potential function of NOTUM. Western blotting and reverse transcription-quantitative PCR were conducted to detect the protein and mRNA expression levels of NOTUM in different tissues or cell lines. The occurrence and development of COAD was detected after NOTUM knockdown lentivirus administration. The apoptosis of COAD was also observed. SKL2001 was applied to examine whether the role of NOTUM was regulated by Wnt. GEPIA analysis demonstrated that NOTUM expression in COAD tumor tissue was higher compared with in normal tissues. Pair-wise gene correlation analysis identified a potential relationship between NOTUM and Wnt. NOTUM protein and mRNA expression levels in colon carcinoma tissues and RKO cells were increased. NOTUM knockdown lentivirus serves a role in inhibiting COAD development by reducing tumor proliferation, reducing tumor size, and increasing the level of apoptosis in vitro and in vivo. Moreover, NOTUM could increase apoptosis in COAD, which was regulated by FAS, and SKL2001 blocked the progress of apoptosis after NOTUM regulation by NOTUM knockdown lentivirus in vitro and in vivo. Collectively, the present results suggested that NOTUM may be able to regulate the apoptosis of COAD, and that Wnt may be the down-stream target signaling of NOTUM in apoptosis.


Assuntos
Apoptose/genética , Neoplasias do Colo , Esterases/genética , Via de Sinalização Wnt/genética , Receptor fas/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Animais , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Esterases/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Receptor fas/metabolismo
6.
Sci Rep ; 8(1): 10461, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29992971

RESUMO

Recent studies have shown that miR-494-3p is oncogene and has a central role in many solid tumors; however, the role of miR-494-3p in the progression and prognosis of hepatocellular carcinoma (HCC) remains unknown. In this study, it was found that miR-494-3p was up-regulated in HCC tissues. The high level of miR-494-3p in HCC tumors was correlated with aggressive clinicopathological characteristics and predicted poor prognosis in HCC patients. Functional study demonstrated that miR-494-3p significantly promoted HCC cell metastasis in vitro and vivo. Since phosphoinositide 3-kinase/protein kinase-B (PI3K/AKT) signaling is a basic oncogenic driver in HCC, a potential role of miR-494-3p was explored as well as its target genes in PI3K/AKT activation. Of all the predicted target genes of miR-494-3p, the tumor-suppressor phosphatase and tensin homolog (PTEN) were identified. In conclusion, the data we collected could define an original mechanism of PI3K/AKT hyperactivation and sketch the regulatory role of miR-494-3p in suppressing the expression of PTEN. Therefore, targeting miR-494-3p could provide an effective therapeutic method for the treatment of the disease.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/fisiologia , PTEN Fosfo-Hidrolase/antagonistas & inibidores , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/análise , Pessoa de Meia-Idade , Metástase Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Análise de Sobrevida
7.
Mol Med Rep ; 13(3): 2208-14, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26782265

RESUMO

The overexpression or abnormal activation of cyclo­oxygenase­2 (COX­2) has been reported in pancreatic cancer cells. NS­398, a selective inhibitor of COX­2, is unable to inhibit pancreatic cancer cell proliferation, as determined by a Cell Counting Kit 8 assay. However, it does increase cancer cell invasiveness, and therefore the invasiveness of the PANC­1 cells was determined, along with the activation of P38, which was assessed by western blotting. In the present study, to evaluate the mechanisms underlying the action of NS­398 in pancreatic cancer cells, PANC­1 cells were treated with NS­398, and the invasion signaling pathways of cluster of differentiation (CD)147­matrix metalloproteinase (MMP)­2 and mitogen­activated protein kinases were evaluated. The results showed that NS­398­induced the expression of CD147 and MMP­2 via the activation of P38, which was involved in antiproliferative activity and induced pancreatic cancer cell invasiveness. The PANC­1 cells were also co­treated with CD147 small interfering (si)RNA and NS­398, and it was found that the NS­398­induced activation of P38 was not inhibited by CD147 siRNA, however, the expression of MMP­2 was inhibited. CD147 siRNA inhibited the invasiveness of the pancreatic cancer cells induced by NS­398, but also restored NS­398­induced antiproliferative activity. These data indicated that P38 in the pancreatic cancer cells was non­specifically activated by NS­398. This activation induced the expression of CD147­MMP­2, opposed the antiproliferative activity of NS­398 and increased the invasiveness of the PANC­1 cells.


Assuntos
Basigina/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Nitrobenzenos/farmacologia , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/patologia , Sulfonamidas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Invasividade Neoplásica , Nitrobenzenos/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Piridinas/farmacologia , RNA Interferente Pequeno/metabolismo , Sulfonamidas/uso terapêutico
8.
Arch Med Sci ; 10(3): 419-24, 2014 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-25097569

RESUMO

INTRODUCTION: Several studies have reported the relationship between the STAT4 rs7574865G > T polymorphism as a susceptibility factor to ulcerative colitis (UC). However, the results have been controversial. Therefore, we conducted this meta-analysis to obtain the most reliable estimate of the association. MATERIAL AND METHODS: PubMed, Embase and Web of Science databases were searched. Crude odds ratios (OR) with 95% confidence intervals (CI) were extracted and pooled to assess the strength of the association between the STAT4 rs7574865G > T polymorphism and risk of UC. A total of five eligible studies including 1532 cases and 3786 controls based on the search criteria were involved in this meta-analysis. RESULTS: We observed that the STAT4 rs7574865G > T polymorphism was significantly correlated with UC risk when all studies were pooled into the meta-analysis (the allele contrast model: OR = 1.13, 95% CI = 1.02-1.25; the heterozygote codominant model: OR = 1.22, 95% CI = 1.04-1.43; the dominant model: OR = 1.25, 95% CI = 1.07-1.45). In the stratified analysis by ethnicity, significant associations were observed in Spanish for the allele contrast model (OR = 1.20; 95% CI = 1.04-1.39), for the homozygote codominant model (OR = 1.57; 95% CI = 1.07-2.31), for the dominant model (OR = 1.20; 95% CI = 1.01-1.43), and for the recessive model (OR = 1.50; 95% CI = 1.03-2.19). CONCLUSIONS: This meta-analysis suggests that the STAT4 rs7574865G > T polymorphism is a low-penetrant risk factor for UC, especially in Spanish.

9.
Tumour Biol ; 35(12): 12157-63, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25168367

RESUMO

Recent studies have shown that microRNAs, a class of small and noncoding RNA molecules, play crucial roles in the initiation and progression of pancreatic cancer. In the present study, the expression and roles of miR-191 were investigated. Through both gain-of function and loss-of function experiments, a pro-oncogenic function of miR-191 was demonstrated. At the molecular level, bioinformatic prediction, luciferase, and protein expression analysis suggested that miR-191 could inhibit protein levels of UPS10, which suppressed the proliferation and growth of cancer cells through stabilizing P53 protein. Collectively, these data suggest that miR-191 could promote pancreatic cancer progression through targeting USP10, implicating a novel mechanism for the tumorigenesis.


Assuntos
MicroRNAs/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Interferência de RNA , Ubiquitina Tiolesterase/genética , Animais , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Masculino , Camundongos , MicroRNAs/química , NF-kappa B/genética , NF-kappa B/metabolismo , Neoplasias Pancreáticas/metabolismo , Transdução de Sinais , Carga Tumoral , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina Tiolesterase/química
10.
Pancreatology ; 13(1): 72-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23395573

RESUMO

OBJECTIVES: Pancreatic cancer is one of the most aggressive and lethal cancers worldwide and there are few effective treatments. Recently, salinomycin (Sal) was reported to alter proliferation and apoptosis in various tumors. This prompted us to investigate the effect of Sal on pancreatic cancer cells and to explore the possible molecular mechanism in vitro. METHODS: After treatment with Sal, pancreatic cancer cell viability and apoptosis were analyzed by Hoechst 33342 staining and flow cytometry, respectively. Invasion and metastasis of pancreatic cancer cells were assayed by a Transwell migration assay. Flow cytometry was also used to assessed the fraction of CD133(+) cell subpopulations. The expression of proliferating cell nuclear antigen (PCNA), Bcl-2, E-cadherin, and Wnt/ß-catenin signaling-related proteins were detected by RT-PCR and western blot. RESULTS: Sal inhibited the growth and migration of pancreatic cancer cells in vitro in a dose- and time-dependent manner. We found that the proportion of CD133(+) cell subpopulations decreased after treatment with Sal in pancreatic cancer cell lines at the same time. The percentage of apoptotic cells was increased after Sal treatment. Compared with control groups, Bax and E-cadherin were significantly upregulated, and Bcl-2 and PCNA were significantly downregulated in Sal-treated cells. The expression of Wnt/ß-catenin signaling-related proteins (ß-catenin and p-GSK-3ß) was inhibited. CONCLUSIONS: These results indicate that Sal could influence the cell growth and migration in pancreatic cancer cells in vitro, which may occur by inhibition of Wnt/ß-catenin signaling.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Piranos/farmacologia , Antígeno AC133 , Antígenos CD , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Glicoproteínas/antagonistas & inibidores , Humanos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Peptídeos/antagonistas & inibidores
11.
Asian Pac J Cancer Prev ; 13(7): 3203-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22994734

RESUMO

BACKGROUNDS: To investigate the inhibiting effects of multi-target anti-microRNA antisense oligonucleotide (MTg-AMOs) on proliferation and migration of human gastric cancer cells. METHODS: Single anti-microRNA antisense oligonucleotides (AMOs) and MTg-AMOs for miR-221, 21, and 106a were designed and transfected into SGC7901, a gastric cancer cell line, to target the activity of these miRNAs. Their expression was analyzed using stem-loop RT-PCR and effects of MTg-AMOs on human gastric cancer cells were determined using the following two assay methods: CCK8 for cell proliferation and transwells for migration. RESULTS: In the CCK-8 cell proliferation assay, 0.6 µmol/L was selected as the preferred concentration of MTg-AMOs and incubation time was 72 hours. Under these experimental conditions, MTg-AMOs demonstrated better suppression of the expression of miR-221, miR-106a, miR-21 in gastric cancer cells than that of single AMOs (P = 0.014, 0.024; 0.038, respectively). Migration activity was also clearly decreased as compared to those in randomized and blank control groups (28 ± 4 Vs 54 ± 3, P <0.01; 28 ± 4 Vs 59 ± 4, P < 0.01). CONCLUSIONS: MTg-AMOs can specifically inhibit the expression of multiple miRNAs, and effectively antagonize proliferation and migration of gastric cancer cells promoted by oncomirs.


Assuntos
Movimento Celular/efeitos dos fármacos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Oligodesoxirribonucleotídeos Antissenso/genética , Oligodesoxirribonucleotídeos Antissenso/farmacologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Processos de Crescimento Celular/efeitos dos fármacos , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sincalida/genética , Transfecção/métodos
12.
PLoS One ; 7(5): e37854, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22662237

RESUMO

AIMS: Invasion and metastasis are major reasons for pancreatic cancer death and identifying signaling molecules that are specifically used in tumor invasion is of great significance. The purpose of this study was to elucidate the role of GEP100 in pancreatic cancer cell invasion and metastasis and the corresponding molecular mechanism. METHODS: Stable cell lines with GEP100 knocked-down were established by transfecting GEP100 shRNA vector into PaTu8988 cells and selected by puromycin. qRT-PCR and Western blot were performed to detect gene expression. Matrigel-invasion assay was used to detect cancer cell invasion in vitro. Liver metastasis in vivo was determined by splenic injection of indicated cell lines followed by spleen resection. Immunofluorescence study was used to detect the intracellular localization of E-cadherin. RESULTS: We found that the expression level of GEP100 protein was closely related to the invasive ability of a panel of 6 different human pancreatic cancer cell lines. Down-regulation of GEP100 in PaTu8988 cells significantly decreased invasive activity by Matrigel invasion assay, without affecting migration, invasion and viability. The inhibited invasive activity was rescued by over-expression of GEP100 cDNA. In vivo study showed that liver metastasis was significantly decreased in the PaTu8988 cells with GEP100 stably knocked-down. In addition, an epithelial-like morphological change, mimicking a mesenchymal to epithelial transition (MET) was induced by GEP100 down-regulation. The expression of E-cadherin protein was increased 2-3 folds accompanied by its redistribution to the cell-cell contacts, while no obvious changes were observed for E-cadherin mRNA. Unexpectedly, the mRNA of Slug was increased by GEP100 knock-down. CONCLUSION: These findings provided important evidence that GEP100 plays a significant role in pancreatic cancer invasion through regulating the expression of E-cadherin and the process of MET, indicating the possibility of it becoming a potential therapeutic target against pancreatic cancer.


Assuntos
Caderinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Fatores de Troca do Nucleotídeo Guanina/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Animais , Comunicação Celular , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Neoplasias Pancreáticas/patologia
13.
Gastroenterol Res Pract ; 2012: 405425, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22550478

RESUMO

Objective. Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. To observe the effect of eradicating Helicobacter pylori (H. pylori) and the treatment of duodenal ulcer by 2 kinds of modified sequential therapy through comparing with that of 10-day standard triple therapy. Methods. A total of 210 patients who were confirmed in duodenal ulcer active or heal period by gastroscopy and H. pylori positive confirmed by rapid urease test, serum anti-H. pylori antibody (ELASE), or histological examination enrolled in the study. All the patients were randomly divided into three groups: group A (70 cases) and group B (70 cases) were provided 10-day modified sequential therapy; group C (70 cases) was provided 10-day standard triple therapy. Patients of group A received 20 mg of Esomeprazole, 500 mg of Clarithromycin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group B received 20 mg of Esomeprazole, 1000 mg of Amoxicillin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group C received 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for standard 10-day therapy. All drugs were given twice daily. H. pylori eradication rate was checked four to eight weeks after taking the medicine by using a (13)C urea breath test. In the first, second, third, seventh, twenty-first, thirty-fifth days respectively, the symptoms of patients such as epigastric gnawing, burning pain, and acidity were evaluated simultaneously. Results. Overall, 210 patients accomplished all therapy schemes, 9 case patients were excluded. The examination result indicated that the H. pylori eradication rate of each group was as follows: group A 92.5% (62/67), group B 86.8% (59/68), and group C 78.8% (52/66). The H. pylori eradication rate of group A was slightly higher than group B (P < 0.05) and both of them were obviously higher than group C (P < 0.05). Modified sequential therapy was significantly more effective in patients with clarithromycin-resistant strains (80%/67% versus 31%; P = 0.02). Symptoms improvement: all the three groups could improve the symptoms such as epigastric gnawing, burning pain, and acidity since the first day. There was no significant difference in total score descending of symptoms between each group (P > 0.05). Conclusions. All the three therapy schemes could alleviate symptoms of duodenal ulcer patients in China efficiently. But as far as eradicating H. pylori is concerned, the modified sequential therapy was better than standard triple therapy, especially the therapy scheme used in group A.

14.
World J Gastroenterol ; 18(3): 275-8, 2012 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-22294831

RESUMO

AIM: To evaluate the efficacy of intraductal ultrasonography (IDUS) in the diagnosis of non-opaque, common bile duct stones. METHODS: A total of 183 patients (102 males, mean age 73 years; 81 females, mean age 70 years) with suspected common bile duct stones diagnosed through abdominal computed tomography (CT), magnetic resonance imaging (MRI), and abdominal Type-B ultrasound were included in the study. The diagnosis was confirmed through endoscopic retrograde cholangiopancreatography (ERCP) followed by IDUS. RESULTS: A total of 183 patients with suspected common bile duct (CBD) stones were included in the study as follows: 36 patients with high-density CBD stones, 68 patients with sand-like stones, 44 patients with low-density stones, 21 patients with ampullary cancer, and 14 patients with pancreatic cancer. Conventional imaging revealed 124 cases of choledochectasia, and only 36 cases of suspected CBD stones; ERCP revealed 145 cases of CBD stones with three missed diagnoses. IDUS revealed 148 cases of CBD stones, 21 cases of ampullary tumors, and 14 cases of pancreatic cancer. CONCLUSION: IDUS was more effective in the diagnosis of bile duct stones than ERCP, upper abdominal CT or upper abdominal MRI.


Assuntos
Ducto Colédoco/diagnóstico por imagem , Endossonografia/métodos , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/diagnóstico , Idoso , Colangiopancreatografia Retrógrada Endoscópica/métodos , Feminino , Cálculos Biliares/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
15.
Hepatogastroenterology ; 59(113): 296-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22260837

RESUMO

BACKGROUND/AIMS: This study aimed to compare the 7d triple therapy with 3d and 5d triple therapies, to observe the effect of eradicating Helicobacter pylori (Hp) on treating duodenal ulcers. METHODOLOGY: One hundred and sixteen patients who were confirmed duodenal ulcer active period and Hp positive were enrolled in the study. All the patients were divided into three groups: 3d group (n=39), 5d group (n=37) and 7d control group (n=40). All three groups were provided triple therapy first: rabeprazole, 10mg + furazolidone, 100mg + clarithromycin 250mg, twice a day for three days, five days and seven days, respectively. Then rabeprazole 10mg was provided once a day. Following the treatment, 13C urea breath test was performed to observe the Hp eradication rate. The symptoms of patients such as epigastralgia, burning pain and acidity were evaluated. RESULTS: The Hp eradication rate was: 3d group 76% (28/37), 5d 89% (31/35) and 7d 91% (32/35). There was no significant difference between 5d and 7d group (p>0.05). But the rate of groups 5d and 7d was significantly higher than group 3d (p<0.05). All the three groups showed an improvement in symptoms such as epigastralgia, burning pain and acidity. CONCLUSIONS: All three therapy schemes could alleviate symptoms of duodenal ulcer patients efficiently. But as far as eradicating Hp concerned, 5d and 7d therapies were better than 3d.


Assuntos
2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , Antibacterianos/administração & dosagem , Antiulcerosos/administração & dosagem , Claritromicina/administração & dosagem , Úlcera Duodenal/tratamento farmacológico , Furazolidona/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis/efeitos adversos , Adolescente , Adulto , Idoso , Antibacterianos/efeitos adversos , Antiulcerosos/efeitos adversos , Testes Respiratórios , Distribuição de Qui-Quadrado , China/epidemiologia , Claritromicina/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Úlcera Duodenal/diagnóstico , Úlcera Duodenal/epidemiologia , Úlcera Duodenal/microbiologia , Feminino , Furazolidona/efeitos adversos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/efeitos adversos , Rabeprazol , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
PLoS One ; 7(12): e50638, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23284640

RESUMO

The anti-tumor antibiotic salinomycin (Sal) was recently identified as a selective inhibitor of breast cancer stem cells; however, the effect of Sal on hepatocellular carcinoma (HCC) is not clear. This study aimed to determine the anti-tumor efficacy and mechanism of Sal on HCC. HCC cell lines (HepG2, SMMC-7721, and BEL-7402) were treated with Sal. Cell doubling time was determinated by drawing growth curve, cell viability was evaluated using the Cell Counting Kit 8. The fraction of CD133(+) cell subpopulations was assessed by flow cytometry. We found that Sal inhibits proliferation and decreases PCNA levels as well as the proportion of HCC CD133(+)cell subpopulations in HCC cells. Cell cycle was analyzed using flow cytometry and showed that Sal caused cell cycle arrest of the various HCC cell lines in different phases. Cell apoptosis was evaluated using flow cytometry and Hoechst 33342 staining. Sal induced apoptosis as characterized by an increase in the Bax/Bcl-2 ratio. Several signaling pathways were selected for further mechanistic analyses using real time-PCR and Western blot assays. Compared to control, ß-catenin expression is significantly down-regulated upon Sal addition. The Ca(2+) concentration in HCC cells was examined by flow cytometry and higher Ca(2+) concentrations were observed in Sal treatment groups. The anti-tumor effect of Sal was further verified in vivo using the hepatoma orthotopic tumor model and the data obtained showed that the size of liver tumors in Sal-treated groups decreased compared to controls. Immunohistochemistry and TUNEL staining also demonstrated that Sal inhibits proliferation and induces apoptosis in vivo. Finally, the role of Sal on in vivo Wnt/ß-catenin signaling was evaluated by Western blot and immunohistochemistry. This study demonstrates Sal inhibits proliferation and induces apoptosis of HCC cells in vitro and in vivo and one potential mechanism is inhibition of Wnt/ß-catenin signaling via increased intracellular Ca(2+) levels.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Piranos/farmacologia , Antígeno AC133 , Animais , Antígenos CD/metabolismo , Cálcio/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glicoproteínas/metabolismo , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Masculino , Camundongos , Peptídeos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Wnt/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismo
17.
Hepatogastroenterology ; 58(110-111): 1511-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21940310

RESUMO

BACKGROUND/AIMS: Hedgehog (Hh) pathway has been considered as a therapy target for various cancer entities. However, its mechanism in colorectal cancer is still unclear. METHODOLOGY: We analyzed the expression of Hh pathway members in colorectal adenomas and cancer cell lines and then studied its relationship with survival of colorectal cancer cells through inhibiting Hh pathway by cyclopamine. Moreover, we studied the regulation of Gli1 on insulin-like growth factor binding protein 6 (IGFBP6) and B-cell CLL/lymphoma 2 (Bcl-2) genes at the level of transcription by XChIP and cyclopamine inhibition assay. RESULTS: Sonic hedgehog (Shh), Smoothened (Smo), patched (Ptch) and Gli1 genes mRNA were expressed in SW116 cells. Gli1 bound to promoter regions of Bcl-2 and IGFBP6 genes, cyclopamine inhibited proliferation and induced apoptosis through inhibiting the transcriptions of IGFBP6 (p=0.003), proliferating cell nuclear antigen (PCNA) (p=0.014) and Bcl-2 (p=0.013), and increasing that of BCL2-associated X protein (Bax) and BCL2-antagonist/killer 1 (Bak1) (p=0.003 and 0.001, respectively) in SW116 cells. CONCLUSIONS: Hh pathway is aberrant activation in part colorectal carcinomas cell lines and its inhibitor may be an effectual agent for colorectal cancer chemoprevention. It may be one of the mechanisms that Gli1 maintained cell survival by binding the promoter regions and facilitating transcription of IGFBP6 and Bcl-2 genes.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Proteínas Hedgehog/genética , Fatores de Transcrição/genética , Alcaloides de Veratrum/farmacologia , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/patologia , Genes bcl-2/genética , Humanos , Técnicas In Vitro , Proteína 6 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Receptores Patched , Receptor Patched-1 , Receptores de Superfície Celular/genética , Receptores Acoplados a Proteínas G/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Receptor Smoothened , Transcrição Gênica , Proteína GLI1 em Dedos de Zinco
18.
Med Oncol ; 28 Suppl 1: S189-96, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21053104

RESUMO

There has been few report discussing the expression and function of miR-212 in gastric cancer (GC). The aim of this pilot study was to investigate the expression of miR-212 in both gastric cancer tissues and gastric cancer cells and further explores the possible reasons for this change and the impact on the development of gastric cancer. qRT-PCR was used to detect the expression of miR-212 in primary GC tissues, adjacent normal tissues, gastric cancer cell lines BGC-823, SGC-7901, MKN-45, and normal gastric mucosa cell line GES. The expression of miR-212 was evaluated before and after treatment with methylation inhibitor-5-Aza-2'-deoxycitidine (5-Aza-dC), finally anti-miRNA and dual luciferase reporter assay were used to prove that MYC is a target gene of miR-212. The results showed that a significant reduction of miR-212 expression in GC tissues was observed compared to that in normal tissues (P = 0.002). At the same time, miR-212 expression level in normal gastric mucosa cell line GES was higher than that of in gastric cancer cell lines BGC-823, SGC-7901, and MKN-45 (P = 0.015, 0.008, 0.044, respectively). Computer sequence analysis showed the hypermethylation of CpG islands(CPI) in the promoter regions of miR-212 led to the lower expression of miR-212 in gastric cell strains (BGC-823 and SGC-7901). MiR-212 expression was significantly recovered after treatment with methylation inhibitor 5-Aza-dC (P = 0.016, 0.000, 0.015, respectively). Then, the results of AMOs transfection and dual luciferase reporter assay showed that Myc is a target of miR-212, which will be helpful to verify the function of miR-212 in carcinogenesis. The conclusion could be deduced from the study that decreased expression of miR-212 may be due to hypermethylation of CPI in gastric cancer cells, and miR-212 might act on the progression of gastric cancer through the potential target gene Myc.


Assuntos
Metilação de DNA/fisiologia , Regulação para Baixo/fisiologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias Gástricas/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Projetos Piloto , Neoplasias Gástricas/genética
19.
Dig Dis Sci ; 56(6): 1645-55, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21132365

RESUMO

BACKGROUND: The cellular repressor of E1A-stimulated genes (CREG), a secreted glycoprotein, has been studied with human embryonic carcinoma cells, vascular smooth muscle cells, and NIH3T3 fibroblasts. However, its relationship to tumor cell proliferation and metastasis has not been examined in human gastric cancers (GC) until now. AIM: To investigate the expression of CREG in GC and its association with GC cell proliferation and metastasis. METHODS: Forty-two cases of GCs, matched normal gastric tissues, and the human gastric cancer cell lines BGC-823, SGC-7901, MKN45, normal gastric mucosa cell line GES, and HUVEC cell line ECV304 were used to analyze CREG expression at the level of mRNA and protein. The expression of CREG was then further examined by immunohistochemistry in 42 GC tissues, and the correlation between the level of CREG and the pathological and clinical data was evaluated. Finally, we down-regulated the expression of CREG in GC cells with specific siRNA, and assessed the role of CREG in the proliferation and metastasis/invasion of the GC cell line. RESULTS: The level of CREG was found to be higher in malignant GC tissues and cells compared to adjacent normal tissues and normal gastric cells (p < 0.001). Additionally, the expression levels of CREG were positively correlated with tumor clinical stage (p = 0.001), tumor metastasis (p < 0.001), and stages of tumor infiltration (p = 0.019). Furthermore, by using siRNA, we found that the down-regulated expression of CREG inhibited the proliferation of GC cells (p < 0.05), and migration of both GC cells (p = 0.001). CONCLUSIONS: Our data suggest that CREG plays an important role in gastric cancer cell proliferation and metastasis and that CREG may be a potential therapeutic target for GC.


Assuntos
Regulação Neoplásica da Expressão Gênica/fisiologia , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular , Movimento Celular , Proliferação de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Repressoras/genética , Neoplasias Gástricas/classificação , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
20.
J Carcinog ; 8: 13, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19736394

RESUMO

BACKGROUND: Aberrant activation of Hedgehog (Hh) signaling pathway has been reported to be related to malignant biological behavior of pancreatic cancer but its mechanism is unclear yet. Since IGF pathway and Bcl-2 family are involved in proliferation and apoptosis of pancreatic cancer cells, we hypothesize that they are possibly associated with Hh pathway. MATERIALS AND METHODS: We studied the relationship of Shh-Gli1 signaling pathway with proliferation and apoptosis of pancreatic cancer cells and the regulation of transcription factor Gli1 to insulin-like growth factor binding protein 6 (IGFBP6) and Bcl-2 genes at the level of transcription. RESULTS: Sonic hedgehog (Shh), Smoothened (Smo), patched and Gli1 were expressed in pancreatic cancer cells. Cyclopamine inhibited cell proliferation at low concentration and induced apoptosis at high concentration. Effect of RNA interference (RNAi) for Gli1 to cell survival is mainly due to proliferation inhibition though involved in apoptosis. The transcription factor Gli1 bound to promoter regions of Bcl-2 and IGFBP6 genes and the levels of IGFBP6, proliferating cell nuclear antigen (PCNA) and Bcl-2 messenger RNA (mRNA) were decreased as well as Gli1 mRNA significantly by cyclopamine or RNAi in cultured pancreatic cancer cells (p < 0.01). Finally PCNA, IGFBP6 and Bcl-2 mRNA were upregulated as well as Shh or Gli1 in pancreatic cancer tissues (p < 0.01). CONCLUSIONS: Our study reveals that Gli1 maintained cell survival by binding the promoter regions and facilitating transcription of IGFBP6 and Bcl-2 genes in a parallel manner in pancreatic cancer cells and suggests it may be one of the mechanisms of Shh-Gli1 signaling pathway in pancreatic cancer.

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