Publications by authors named "Guifang Lu"

31 Publications

Delphinidin modulates JAK/STAT3 and MAPKinase signaling to induce apoptosis in HCT116 cells.

Environ Toxicol 2021 May 6. Epub 2021 May 6.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Delphinidin is an anthocyanin that belongs to the group of flavonoids that exert numerous biological activities. However, the molecular mechanisms underlying the anticancer effects of delphinidin remain poorly understood. In our study we analyzed delphinidin modulate STAT-3 and MAPKinase signaling thereby inhbits cell proliferation and promote apoptosis. Our study demonstrated that delphinidin treatment significantly reduced the viability of human colon cancer HCT116 in a concentration-dependent manner. We noticed that delphinidin effectively induced oxidative stress-mediated apoptosis by generating intracellular ROS, decreasing antioxidant levels, inducing lipid peroxidation, and single-strand break on colon cancer cells. In this study, we observed that delphinidin treatment alters the mitochondrial membrane potential, thereby induces apoptosis was closely associated with the induction of pro-apoptotic Bax, Caspase- 3,8 & 9, cytochrome C, and inhibition of anti-apoptotic protein expression. Studies on STAT-3 and MAPKinase signaling showed delphinidin inhibited the phosphorylation of these transcription factors' activity. Inhibition of STAT-3, p38, and ERK1/2 phosphorylation and modulation pro-apoptotic protein expression might be responsible for the anticancer activity of delphinidin in colon cancer cells.
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http://dx.doi.org/10.1002/tox.23152DOI Listing
May 2021

Endoscopy-assisted magnetic compression anastomosis for rectal anastomotic atresia.

Endoscopy 2021 Jan 27. Epub 2021 Jan 27.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.

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http://dx.doi.org/10.1055/a-1322-1899DOI Listing
January 2021

Screening value for gastrointestinal lesions of magnetic-controlled capsule endoscopy in asymptomatic individuals.

J Gastroenterol Hepatol 2021 May 14;36(5):1267-1275. Epub 2020 Oct 14.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background And Aim: Most patients with gastric tumors and precancerous lesions are asymptomatic, which often results in delayed diagnosis and treatment. Compared with conventional gastroscopy and capsule endoscopy, magnetic-controlled capsule endoscopy is a non-invasive, effective, and cost-efficient diagnostic modality for gastric examination. We retrospectively investigated magnetic-controlled capsule endoscopy as a screening tool for gastrointestinal lesions (particularly gastric tumors and precancerous lesions) in asymptomatic individuals.

Methods: In this retrospective study, 1757 patients who voluntarily underwent magnetic-controlled capsule endoscopy between January and December 2019 at nine medical centers across Shaanxi province based on strict inclusion and exclusion criteria were enrolled. The primary outcomes were gastric tumor and precancerous lesion detection rates and procedural safety.

Results: The upper and lower gastrointestinal lesion detection rates were 98.35% (1728/1757) and 21.61% (78/361), respectively; 2.28% of patients were diagnosed with gastric tumors including gastric cancer (4/1757) and submucosal tumors (36/1757). Three types of precancerous lesions were found in 591 patients (33.64%), including chronic atrophic gastritis (23.16%), gastric polyp (10.98%), and gastric ulcer (2.96%). For patients aged over 40 years, the detection rate of precancerous lesions was higher (14.36% vs 42.58%, P < 0.001). No patient was diagnosed with small intestinal cancer. No adverse events occurred.

Conclusions: Magnetic-controlled capsule endoscopy could be used as a promising novel screening modality for diagnosis of gastrointestinal lesions in asymptomatic individuals, specifically gastric tumors and precancerous lesions, with the advantages of safety, non-invasiveness, effectiveness, and cost-efficiency.
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http://dx.doi.org/10.1111/jgh.15282DOI Listing
May 2021

The Prognosis Analysis of Liver Cirrhosis with Acute Variceal Bleeding and Validation of Current Prognostic Models: A Large Scale Retrospective Cohort Study.

Biomed Res Int 2020 16;2020:7372868. Epub 2020 Aug 16.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: Acute variceal bleeding is a major cause of death in liver cirrhosis. This large scale retrospective cohort study aims to analyze the prognosis of patients with cirrhosis and acute variceal bleeding and to validate the current prognostic models.

Methods: Patients with cirrhosis and acute variceal bleeding were enrolled from Jan 2019 to March 2020. The independent prognostic factors for in-hospital death were identified by logistic regression analyses. Area under curves (AUCs) was compared among Child-Pugh, cirrhosis acute gastrointestinal bleeding (CAGIB) score, and model for end-stage liver disease (MELD) and neutrophil-lymphocyte ratio (NLR) scores.

Results: Overall, 379 patients with liver cirrhosis and acute variceal bleeding were consecutively evaluated. The majority of the patients were males (59.1%) and the mean age of all patients were 53.7 ± 1.3 years (range 14-89). Hepatitis B virus (HBV) was the most common underlying cause of liver cirrhosis (54.1%). 72 (19%) patients had hepatocellular carcinoma. Multivariate logistic regression analyses showed that age, HCC, WBC, total serum bilirubin, serum creatinine, and ALT were independently associated with in-hospital death. And the odds ratios (ORs) for in-hospital death were 1.066 (95% CI 1.017-1.118, = 0.008), 7.19 (95% CI 2.077-24.893, = 0.001), 1.123 (95% CI 1.051-1.201, = 0.001), 1.014 (95% CI 1.005-1.023, = 0.003), 1.012 (95% CI 1.004-1.021, = 0.006), and 1.005 (95% CI 1.000-1.009, = 0.036), respectively. In the whole cohort with HCC patients, the AUCs of Child-Pugh, CAGIB, MELD and NLR scores were 0.842 (95% CI 0.801-0.878), 0.840 (95% CI 0.799-0.876), 0.798 (95% CI 0.754-0.838), and 0.688 (95% CI 0.639-0.735), respectively. The differences were statistically significant between Child-Pugh and NLR scores ( = 0.0118), and between CAGIB and NLR scores ( = 0.0354).

Conclusion: Child-Pugh and CAGIB scores showed better predictive performance for prognosis of patients with cirrhosis and acute variceal bleeding than NLR scores.
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http://dx.doi.org/10.1155/2020/7372868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448238PMC
May 2021

LncRNA SNAI3-AS1 promotes PEG10-mediated proliferation and metastasis via decoying of miR-27a-3p and miR-34a-5p in hepatocellular carcinoma.

Cell Death Dis 2020 08 11;11(8):685. Epub 2020 Aug 11.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, P. R. China.

During recent years, long noncoding RNAs (lncRNAs) have received focal attention due to their important function in cancer regulation. Though the relation between lncRNA SNAI3-AS1 and the development of hepatocellular carcinoma (HCC) has been described in our previous study, the role and the exact mechanism of SNAI3-AS1 are still unclear. In this study, qRT-PCR analysis revealed that the expression of SNAI3-AS1 was elevated and was correlated with the levels of PEG10 in HCC tissues. Through functional experiments, we determined that knockdown of SNAI3-AS1 and PEG10 inhibited the proliferation and metastasis, whereas overexpression of SNAI3-AS1 and PEG10 promoted the proliferation and metastasis of HCC cells. In addition, rescue experiments confirmed that upregulation of PEG10 partially restored cell function inhibition induced by SNAI3-AS1 knockdown. Therefore, we hypothesized that PEG10 may be regulated by SNAI3-AS1, which in turn mediates the malignant biological processes of HCC cells regulated by PEG10. Further bioinformatics analysis and mechanistic experiments showed that SNAI3-AS1 functions as a competing endogenous RNA (ceRNA) to activate PEG10 by acting as a sponge for miR-27-3p and miR-34a-5p. In summary, our study revealed that SNAI3-AS1 is a tumor regulator of PEG10 in the progression of HCC, and may contribute to the improvement of HCC diagnosis and therapy.
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http://dx.doi.org/10.1038/s41419-020-02840-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442791PMC
August 2020

Telephone-Based Reeducation of Drug Administration for Eradication: A Multicenter Randomized Controlled Study.

Gastroenterol Res Pract 2020 31;2020:8972473. Epub 2020 Jul 31.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

Poor adherence to treatment instructions may play an important role in the failure of eradication. The aim of this study was to evaluate the effects of telephone-based reeducation on 14-day quadruple . eradication therapy. In total, 162 patients were randomly assigned (1 : 1) to either the intervention group (patients received telephone-based reeducation on the 4, 7, and 10 days of the course) or the control group (patients received instructions only at the time of getting the prescriptions). All patients received a 14-day quadruple . eradication therapy. The primary outcome was the . eradication rate. The secondary outcomes included the symptom relief rates and the incidence rates of adverse events. Seventy-five patients in the reeducation group and 74 patients in the control group completed the follow-up. The . eradication rate in the reeducation group was statistically higher than that in the control group (intention-to-treat: 72.8% vs. 50.6%, = 0.006; per-protocol: 78.7% vs. 55.4%, = 0.003). However, the symptom relief rates and the adverse event rates in these two groups were not significantly different. Overall, the results from this study suggest that telephone-based reeducation can be potentially applied to improve the . eradication rate in clinical practice, without significantly increasing the adverse effects.
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http://dx.doi.org/10.1155/2020/8972473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415080PMC
July 2020

THBS4 promotes HCC progression by regulating ITGB1 via FAK/PI3K/AKT pathway.

FASEB J 2020 08 22;34(8):10668-10681. Epub 2020 Jun 22.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China.

Our research aims to identify the role of thrombospondin 4 (THBS4) in hepatocellular carcinoma (HCC). First, bioinformatic analysis was applied for detection the expression of THBS4 in HCC samples, and qRT-PCR and western blot were performed to explore the expression of THBS4 in HCC tissues and adjacent samples. Next, colony formation assay and cell viability assay were used to assess the function of THBS4 on HCC cells growth while transwell assay and scratch test were for metastasis. Meanwhile Xenograft tumor models were further conducted to verify the function of THBS4 in HCC. As for mechanism in deep, we investigated the influence of THBS4 on epithelial-mesenchymal transition (EMT) development and the interaction between THBS4 and integrin (ITG) family using multiple experiments, including western blot, immunofluorescence and immunoprecipitation (IP). As a result, our research discovered that the overexpression of THBS4 in both HCC patients' tissues and cell lines mediates HCC cells proliferation and metastasis in vitro and in vivo. In-depth, THBS4 regulated EMT progression and interacted with ITG family to modulate FAK/PI3K/AKT pathway. In conclusion, THBS4 as an oncogene interacts with integrinβ1 (ITGB1) to regulate HCC development via FAK/PI3K/AKT pathway.
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http://dx.doi.org/10.1096/fj.202000043RDOI Listing
August 2020

TRPC1 exacerbate metastasis in gastric cancer via ciRS-7/miR-135a-5p/TRPC1 axis.

Biochem Biophys Res Commun 2020 08 6;529(1):85-90. Epub 2020 Jun 6.

Department of Thoracic Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China. Electronic address:

Metastasis is frequently occurred in end-stage GC. Nevertheless, the initiation and progression of metastasis in GC remains unclear. The transient receptor potential canonical (TRPC) has been confirmed to be crucial for metastasis in many kinds of tumors, including GC. However, the molecular mechanisms regulating TRPC1 is unclear. Therefore, we investigated the role and mechanisms of TRPC1 in GC metastasis. We first evaluated the role of TRPC1 in GC by searching the public database, and tested the expression of TRPC1 in 50 paired GC tissues by qRT-PCR and IHC assays. Then, we generated BGC-823-shTRPC1 cells and MKN-45-TRPC1 cells to investigate the effects of TRPC1 on metastasis in vitro. For the mechanism study, we applied luciferase reporter assay, RNA pull-down assay, as well as RIP assay to validate the interation of ciRS-7, miR-135a-5p and TRPC1 in GC cells. This study, we showed that TRPC1 exacerbate EMT in gastric cancer via ciRS-7/miR-135a-5p/TRPC1 axis, and target TRPC1 could be beneficial for end-stage GC patients.
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http://dx.doi.org/10.1016/j.bbrc.2020.05.181DOI Listing
August 2020

The Effect of Helicobacter pylori Eradication in Patients with Gastroesophageal Reflux Disease: A Meta-Analysis of Randomized Controlled Studies.

Dig Dis 2020 12;38(4):261-268. Epub 2020 May 12.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China,

Aim: Helicobacter pylori infection has been established as a definite risk factor for gastric cancer. However, the consequence of H. pylori eradication on the progression of gastroesophageal reflux disease (GERD) remains controversial. The purpose of our study was to investigate the relationship between H. pylori eradication and the development of GERD.

Methods: A comprehensive, English literature search was performed from January 1990 to April 2019. Only randomized controlled trials (RCT) that evaluated the effect of H. pylori eradication on GERD were included. Meta-analysis of pooled OR was performed using Review Manger 5.1.7.

Results: Seventeen articles with 6,889 subjects (intention-to-treat) that fulfilled the inclusion criteria were finally included in the analysis. Of them, 8 RCTs have the similar study design and inclusion criterion, which included patients with H. pylori infection but without GERD at baseline. The OR for the development of erosive GERD after H. pylori eradication was 1.67 (95% CI 1.12-2.48, p = 0.01). The OR for the development of GERD-related symptoms after H. pylori eradication in eradication group compared with control group was 1.04 (95% CI 0.84-1.29, p = 0.71). In addition, 9 RCTs included patients with both baseline H. pylori infection and GERD. The OR for the healing rates and relapse rates after H. pylori eradication in the H. pylori eradication group vs. control group was 0.92 (95% CI 0.47-1.82, p = 0.82) and 1.12 (95% CI 0.60-2.09, p = 0.71), respectively.

Conclusions: Our meta-analyses showed H. pylori eradication may lead to the development of new erosive GERD. However, eradication of H. pylori may affect neither the healing rates nor relapse rates of preexisting GERD.
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http://dx.doi.org/10.1159/000504086DOI Listing
August 2020

Gastrectomy Versus Endoscopic Resection for Patients With Early-stage Gastric Adenocarcinoma: A Population-based Propensity Matching Study.

J Clin Gastroenterol 2020 Nov/Dec;54(10):871-878

Departments of Gastroenterology.

Background: This study aimed to compare the long-term results of patients who received these therapies.

Materials And Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried in this research for data of patients with early gastric adenocarcinoma who underwent gastrectomy or endoscopic resection from 2007 to 2015. Propensity score matching was selected to generate a balanced cohort. Competing-risk regression analysis was carried out on the matched cohort. Cancer-specific mortality (CSM) and other cause-specific mortality (OCSM) were compared using adjusted subdistribution hazard ratios (SHRs).

Results: In this study, 2214 patients with 191 underwent endoscopic treatment (ET) and 2023 who underwent surgery were identified. After propensity score matching, 474 patients were included in the analysis. The use of ET increased over time in patients, especially for those with cardia diseases. The ratio of 5-year CSM between ET and gastrectomy groups was 13.12% to 14.24% and the ratio of 5-year OCSM between them was 22.48% versus 14.31%. After adjusting for associated clinicopathologic factors, patients in both groups had similar CSM (SHR=0.87, 95% credible interval: 0.47-1.64, P=0.69) and OCSM (SHR=1.59, 95% credible interval: 0.94-2.68, P=0.08) in multivariable analysis.

Conclusion: The long-term prognosis appears equivalent t in patients with endoscopic resection and gastrectomy.
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http://dx.doi.org/10.1097/MCG.0000000000001306DOI Listing
June 2021

[Histone deacetylase 3 inhibitor alleviates alcohol-induced disruption of intestinal epithelial barrier via inhibiting nuclear factor κB].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2019 Sep;35(9):800-805

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. *Corresponding authors, E-mail:

Objective To investigate the role and mechanism of histone deacetylase 3 (HDAC3) in alcohol-induced inflammation and permeability of intestinal epithelial cells. Methods To select the proper concentration of alcohol, differentiated Caco-2 cells were treated with different concentrations (10, 25, 50, 100 and 200 mmol/L) of alcohol, and then cell viability was assayed by MTT assay; the mRNA and protein levels of HDAC3 were analyzed by real-time PCR and Western blot analysis. Differentiated Caco-2 cells were divided into three groups: control group, alcohol group (treatment with 50 mmol/L alcohol for 60 minutes), and alcohol combined with HDAC3 inhibitor group (pretreatment with 2 μmol/L RGFP966 1 hour before alcohol). ELISA was performed to detect tumor necrosis factor α (TNF-α) level in cell supernatant. Transepithelial electrical resistance (TER) was measured using a resistance meter. Western blot analysis was used to determine the protein levels relevant to tight junction (occludin and claudin-1) and NF-κB activation (IκB and phosphorylated NF-κBp65). Results Alcohol at 10, 25 and 50 mmol/L did not affect cell viability. The mRNA and protein expression levels of HDAC3 increased in a dose-dependent manner after alcohol treatment at these concentration s. Compared with the control group, TNF-α and phosphorylated NF-κBp65 levels increased, whereas TER and protein levels of occludin, claudin-1 and IκB decreased in the alcohol group. Compared with the alcohol group, TNF-α and phosphorylated NF-κBp65 levels were reduced, while TER and protein levels of occludin, claudin-1 and IκB were elevated in the alcohol combined with HDAC3 inhibitor group. Conclusion HDAC3 inhibition can attenuate alcohol-induced inflammation and permeability of intestinal epithelial cells, which may be related to the inactivation of NF-κB.
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September 2019

Long non-coding RNA SNAI3-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma by regulating the UPF1/Smad7 signalling pathway.

J Cell Mol Med 2019 09 2;23(9):6271-6282. Epub 2019 Jul 2.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Emerging evidence has indicated that deregulation of long non-coding RNAs (lncRNAs) can contribute to the progression of human cancers, including hepatocellular carcinoma (HCC). However, the role and exact mechanism of most lncRNAs in tumours remains largely unknown. In the current study, we found a novel long non-coding RNA termed SNAI3-AS1 which was generally up-regulated in HCC tissues compared with normal control. Higher expression of SNAI3-AS1 was significantly correlated with shorter overall survival of HCC patients. Knockdown of SNAI3-AS1 inhibited the proliferation and metastasis of HCC cells in vitro, whereas overexpression of SNAI3-AS1 promoted the proliferation and metastasis of HCC cells. Further investigations showed that SNAI3-AS1 could affect HCC tumorigenesis by binding up-frameshift protein 1 (UPF1), regulating Smad7 expression and activating TGF-β/Smad pathway. Functionally, SNAI3-AS1 promoted HCC growth and metastasis by inducing tumour epithelial to mesenchymal transition (EMT). Taken together, these findings showed that SNAI3-AS1 promotes the progression of HCC by regulating the UPF1 and activating TGF-β/Smad pathway.
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http://dx.doi.org/10.1111/jcmm.14513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714236PMC
September 2019

DANCR promotes HCC progression and regulates EMT by sponging miR-27a-3p via ROCK1/LIMK1/COFILIN1 pathway.

Cell Prolif 2019 Jul 30;52(4):e12628. Epub 2019 Apr 30.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Objectives: This research aims to verify that the long non-coding RNA differentiation antagonizing nonprotein coding RNA (LncRNA DANCR) could modulate the proliferation and metastasis of hepatocellular carcinoma (HCC), and it thus may work as a novel biomarker to render new orientation for early diagnosis and clinical therapy of HCC.

Materials And Methods: Firstly, qRT-PCR was used to detect the expression of genes including LncRNA DANCR and miR-27a-3p. Next, MTT assay, Ethynyldeoxyuridine (EdU) analysis and clone formation assay were used for investigating cell growth and proliferation. Meanwhile, transwell assay and wound healing assay were applied to evaluate the capacity of cell metastasis and motility, respectively. In addition, bioinformatic analysis and dual-luciferase reporter assay were applied to analyse molecular interaction. Next, we conducted immunofluorescence and Western blot for mechanic investigation. Last but not the least, xenograft tumours in nude mice were built by subcutaneously injecting Hep3B cells stably transfected with sh-NC and sh-DANCR to detect proliferation and SMMC-7721 cells stably transfected with sh-NC and sh-DANCR to investigate metastasis.

Results: The results of qRT-PCR and bioinformatic analysis revealed the high expression of DANCR in HCC. DANCR accelerated proliferation and metastasis of HCC cells and the knockdown of DANCR had the opposite effect. Meanwhile, xenograft tumours in sh-DANCR group grow slower and have smaller volumes compared with negative control group. Next, the antineoplastic effect of miR-27a-3p on cell growth and motility of HCC was confirmed. In addition, we clarified that DANCR acted as a ceRNA to decoy miR-27a-3p via mediating ROCK1/LIMK1/COFILIN1 pathway. In the end, we validated that DANCR/miR-27a-3p axis regulates EMT progression by cell immunofluorescence and Western blot.

Conclusions: In a word, DANCR promotes HCC development and induces EMT by decoying miR-27a-3p to regulate ROCK1/LIMK1/COFILIN1 pathway.
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http://dx.doi.org/10.1111/cpr.12628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668976PMC
July 2019

Efficacy and safety of steroid in the prevention of esophageal stricture after endoscopic submucosal dissection: A network meta-analysis.

J Gastroenterol Hepatol 2019 Jun 15;34(6):985-995. Epub 2019 Jan 15.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Background And Aim: Even though endoscopic submucosal dissection is an important endoscopic resection technique for gastrointestinal neoplasms, there are chances that postoperative esophageal stricture might take place as a side effect. Steroid applications were reported to be effective for the prevention of stricture formation. Therefore, this study aims to evaluate the efficacy and safety of different steroid applications.

Methods: Eligible studies published on PubMed, the Cochrane Library, Embase, Web of Science, and Chinese Biomedical Literature Database before August 2018 were reviewed. The preventions were divided as placebo/no treatment, long-term oral steroid (LOS), median-term oral steroid, short-term oral steroid, single-dose steroid injection, multiple-dose steroid injection, topical superficial steroid, steroid injection combined with oral steroid, and preemptive endoscopic balloon dilatation. The primary outcomes were postoperative esophageal stricture rate and endoscopic balloon dilatation sessions required. Complications were also analyzed.

Results: A total of 19 studies were included. The network meta-results illustrated that compared with the placebo, all kinds of steroid interventions were associated with lower rates of postoperative esophageal stenosis and less number of endoscopic balloon dilatation sessions. Moreover, combined therapy was no better than single regimen therapy. No significant differences between various steroid applications in the incidence of complications were spotted during this study. Based on the results of the network and clustered ranking, LOS might be the superior prevention for postoperative stricture with satisfying efficacy.

Conclusion: The present study showed that LOS appears to be the optimal prevention method for postoperative stricture formation.
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http://dx.doi.org/10.1111/jgh.14580DOI Listing
June 2019

Long noncoding RNA NNT-AS1 promotes gastric cancer proliferation and invasion by regulating microRNA-363 expression.

J Cell Biochem 2019 04 15;120(4):5704-5712. Epub 2018 Oct 15.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Increasing studies showed that long noncoding RNAs (lncRNAs) had crucial regulatory roles in various tumors, including gastric cancer (GC). Recent studies demonstrated that lncRNA nicotinamide nucleotide transhydrogenase-antisense RNA1 (NNT-AS1) played an important role in several tumors. However, the role and expression of NNT-AS1 in GC progression remain unknown. In our study, we indicated that NNT-AS1 expression was upregulated in GC samples compared with the nontumor tissues. We also showed that NNT-AS1 expression was upregulated in the GC cell lines. Ectopic expression of NNT-AS1 promoted GC cell line HGC-27 cell proliferation, cell cycle progression, and invasion. In addition, we showed that NNT-AS1 acted as a sponge competing endogenous RNA for microRNA-363 (miR-363), which was downregulated in the GC samples and cell lines. miR-363 expression was negatively related with NNT-AS1 expression in GC samples. Upregulated expression of miR-363 suppressed GC cell growth, cycle, and invasion. Furthermore, we reported that elevated expression of NNT-AS1 promoted GC cell proliferation, cycle, and invasion partly by suppressing miR-363 expression. These results indicated that lncRNA NNT-AS1 acted as an oncogene in the development of GC partly by inhibiting miR-363 expression.
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http://dx.doi.org/10.1002/jcb.27855DOI Listing
April 2019

Long non-coding RNA SNHG5 promotes human hepatocellular carcinoma progression by regulating miR-26a-5p/GSK3β signal pathway.

Cell Death Dis 2018 08 30;9(9):888. Epub 2018 Aug 30.

Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China.

Accumulating evidence have suggested that long non-coding RNAs (lncRNAs) had malfunctioning roles in the development of human cancers. The present study aimed to investigate the role of lncRNA small nucleolar RNA host gene 5 (SNHG5) in hepatocellular carcinoma (HCC) progression using human tissues and cell lines. The quantitative real-time PCR results showed that SNHG5 was up-regulated in both HCC tissues and hepatoma cell lines and was closely associated with tumor size, hepatitis B virus infection, histologic grade, TNM stage, and portal vein tumor thrombus (PVTT) in HCC patients. Knockdown of SNHG5 induced apoptosis and repressed cell cycle progression, cell growth, and metastasis in hepatoma cell lines, whereas overexpression of SNHG5 had the opposite effects. In vivo functional assay, xenograft tumors grown from SNHG5-knockdown cells had smaller mean volumes than the tumors grown from negative control cells. Further investigations showed that SNHG5 may act as a competing endogenous RNA by competitively binding miR-26a-5p and thereby modulating the derepression of downstream target GSK3β, which were further confirmed by luciferase reporter assay. Functionally, SNHG5 promotes tumor growth and metastasis by activating Wnt/β-catenin pathway and inducing epithelial to mesenchymal transition (EMT). Taken together, SNHG5 promotes HCC progression by competitively binding miR-26a-5p and regulating GSK3β and Wnt/β-catenin signal pathway.
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http://dx.doi.org/10.1038/s41419-018-0882-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117363PMC
August 2018

The Comparison between Endoscopic Submucosal Dissection and Surgery in Gastric Cancer: A Systematic Review and Meta-Analysis.

Gastroenterol Res Pract 2018 18;2018:4378945. Epub 2018 Feb 18.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.

Aims: There are two treatment modalities for early gastric cancer (EGC)-surgery and endoscopic submucosal dissection (ESD). We aimed to compare the safety and efficacy of ESD with surgery.

Method: The article was performed by searching PubMed databases. Data were extracted using predefined form and odds ratios (OR) with 95% confidence intervals (CI) calculated and value.

Results: 13 studies were identified. The incidence of perforation in two groups was different [OR = 6.18 (95% CI: 1.37-27.98), = 0.02]. The prevalences of synchronous and metachronous cancer in the ESD group were higher than those in the surgery group [OR = 8.52 (95% CI: 1.99-36.56),  = 0.004 and OR = 7.15 (95% CI: 2.95-17.32), < 0.0001]. The recurrence and complete resection rates were different [OR = 6.93 (95% CI: 2.83-16.96), < 0.0001 and OR = 0.32 (95% CI: 0.20-0.52), < 0.00001]. Compared with the surgery group, the hospital stay was shorter [IV = -7.15 (95% CI: -9.08-5.22), < 0.00001], the adverse event rate was lower, and the quality of life (QOL) was better in the ESD group. The difference of bleeding was not found.

Conclusion: ESD appears to be preferable for EGC, due to a lower rate of adverse events, shorter hospital stay, cheaper cost, and higher QOL.
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http://dx.doi.org/10.1155/2018/4378945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835246PMC
February 2018

Targeted next generation sequencing in Chinese colorectal cancer patients guided anti-EGFR treatment and facilitated precision cancer medicine.

Oncotarget 2017 Dec 27;8(62):105072-105080. Epub 2017 Sep 27.

Department of Medical Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, 266005, China.

Objective: Colorectal cancer (CRC) patients with both and wild-type tumors determined by non-next generation sequencing (NGS) testing may still not respond due to the presence of additional mutated genes such as or . In this study, a broad, hybrid capture-based NGS assay was used to identify and additional targetable genetic alterations from Chinese CRC tissues.

Methods: Fifty-seven cases of CRC were enrolled, and all the patients signed the informed consent. In total, 7708 exons of 508 tumor-related genes and 78 introns of 19 frequently rearranged genes were assessed for base substitutions, INDELs, copy number alterations, and gene fusions.

Results: The study found that 50.9% (29/57) of the tumors harbored mutations, 3.5% (2/57) harbored mutations and 3.5% (2/57) harbored mutations. More specifically, 89.7% (26/29) of mutations were located in codon 12. Except for and , anti-EGFR therapy response genetic mutations in (n=2) and (n=1) were found in 4.7% (3/64) of the samples. Actionable alterations were found in (n = 7), (n = 2), (n = 1), and (n = 1).

Conclusions: Our results illustrated that 82.5% (47/57) of the samples harbored at least one actionable genetic alteration identified by NGS. amplifications or mutations, which were identified in 12.3% of the tissues, defined a unique molecular subtype of CRC. The study suggests that high-throughput NGS testing in CRC tissues is a comprehensive and efficient genomic profiling assay to guide personalized therapy.
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http://dx.doi.org/10.18632/oncotarget.21349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739621PMC
December 2017

CENP-H regulates the cell growth of human hepatocellular carcinoma cells through the mitochondrial apoptotic pathway.

Oncol Rep 2017 Jun 26;37(6):3484-3492. Epub 2017 Apr 26.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

The genomic alterations of hepatocellular carcinoma (HCC) are still unclear. Centromere protein-H (CENP-H) has been shown to be associated with many solid tumors. Our previous study found that CENP-H was upregulated in HCC and was related to patient prognosis. However, the biological functions of CENP-H in HCC and the possible underlying mechanisms have not been well elucidated. In the present study, we demonstrated that CENP-H knockdown inhibited the proliferation of Hep3B cells and decreased colony formation ability of single cells in vitro. Furthermore, CENP-H knockdown induced Hep3B cell apoptosis, and apoptotic bodies were observed using transmission electron microscopy. The protein expression of cleaved caspase-3 was upregulated in Hep3B cells after CENP-H knockdown. Additionally, a Bax/Bcl-2 ratio imbalance with a significant increase of Bax and a substantial decrease of Bcl-2 at both the mRNA and protein levels were determined in this study. In an animal experiment, CENP-H knockdown blocked the growth of Hep3B subcutaneous xenografts. Immunohistochemistry revealed that the protein expression of cleaved caspase-3 and Bax was increased, whereas the protein expression of Bcl-2 and Ki-67 was decreased in subcutaneous xenografts of the CENP-H-knockdown group. In summary, CENP-H may be involved in cell proliferation and apoptosis of HCC cells through the mitochondrial apoptotic pathway. Combined with previous studies, the data provide a new perspective on HCC development and progression.
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http://dx.doi.org/10.3892/or.2017.5602DOI Listing
June 2017

MicroRNA-26a inhibits proliferation and metastasis of human hepatocellular carcinoma by regulating DNMT3B-MEG3 axis.

Oncol Rep 2017 Jun 19;37(6):3527-3535. Epub 2017 Apr 19.

Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

miR-26a is known to play an important oncosuppressive role in HCC. However, its regulatory role and relationship with other non-coding RNAs is less clear. In the present study, we report that the expression levels of miR-26a and long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) were frequently downregulated in HCC tissues compared to matched non-malignant tissues. In addition, the expression levels of miR-26a and MEG3 were negatively correlated with the tumor sizes and TNM clinical stage in HCC patients. Overexpression of miR-26a significantly reduced the capacity of proliferation, invasion and migration of HCC cells. Moreover, we demonstrated that DNA methyltransferase 3b (DNMT3B) was a direct target gene of miR-26a. Overexpression of miR-26a suppressed the expression level of DNMT3B. Inhibited expression of DNMT3B showed similar tumor suppressive effects induced by miR-26a upregulation, and resulted in the upregulation of MEG3. Furthermore, we found that the expression levels of DNMT3B were upregulated in the HCC tissues compared with non-malignant tissues, and it was inversely correlated with miR-26a and MEG3 in HCC tissues. Thus, these results provided a plausible link between the observed reduction of miR-26a and MEG3 in HCCs. Together, the present study added miR-26a/DNMT3B/MEG3 axis to the complex mechanisms of HCC development.
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http://dx.doi.org/10.3892/or.2017.5579DOI Listing
June 2017

Lymphangiomatosis of the sigmoid colon - a rare cause of lower gastrointestinal bleeding: A case report and review of the literature.

Oncol Lett 2017 Jan 21;13(1):339-341. Epub 2016 Nov 21.

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

The present study reports the case of a 79-year-old Chinese man who presented to The First Affiliated Hospital of Xi'an Jiaotong University (Xi'an, China) for the treatment of lower gastrointestinal bleeding. Multiple cystic masses in the sigmoid colon were observed with colonoscopy, and through endoscopic ultrasound (EUS), these cystic masses were confirmed to be echo-free and to exhibit septal walls in the submucosal layer; in consequence, lymphangiomatosis of the sigmoid colon was diagnosed. Considering the repeated bleeding, laparoscopy-assisted partial sigmoid colon resection was performed. The excised specimens were multiple vesicular and soft masses of ~1 cm in diameter, which were located in the submucosal layer and were surrounded by flat endothelial cells. Immunohistochemistry revealed that the specimens were positive for the specific lymphatic endothelial marker D2-40. The pathological diagnosis was consistent with the EUS findings. In the 2-year follow-up after the operation, no bleeding or other complications were noticed.
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http://dx.doi.org/10.3892/ol.2016.5399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244848PMC
January 2017

Effects of ghrelin on the apoptosis of human neutrophils in vitro.

Int J Mol Med 2016 Sep 6;38(3):794-802. Epub 2016 Jul 6.

Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.

Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation and the diffuse infiltration of neutrophils into the alveolar space. Neutrophils are abundant, short-lived leukocytes that play a key role in immune defense against microbial infections. These cells die via apoptosis following the activation and uptake of microbes, and will also enter apoptosis spontaneously at the end of their lifespan if they do not encounter pathogens. Apoptosis is essential for the removal of neutrophils from inflamed tissues and for the timely resolution of neutrophilic inflammation. Ghrelin is an endogenous ligand for the growth hormone (GH) secretagogue receptor, produced and secreted mainly from the stomach. Previous studies have reported that ghrelin exerts anti-inflammatory effects in lung injury through the regulation of the apoptosis of different cell types; however, the ability of ghrelin to regulate alveolar neutrophil apoptosis remains largely undefined. We hypothesized that ghrelin may have the ability to modulate neutrophil apoptosis. In this study, to examine this hypothesis, we investigated the effects of ghrelin on freshly isolated neutrophils in vitro. Our findings demonstrated a decrease in the apoptotic ratio (as shown by flow cytometry), as well as in the percentage of cells with decreased mitochondrial membrane potential (ΔΨm) and in the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick‑end labeling-positive rate, accompanied by an increased B-cell lymphoma 2/Bax ratio and the downregulation of cleaved caspase-3 in neutrophils following exposure to lipopolysaccharide (100 ng/ml). However, pre-treatment with ghrelin at a physiological level (100 nM) did not have a notable influence on the neutrophils in all the aforementioned tests. Our findings suggest that ghrelin may not possess the ability to modulate the neutrophil lifespan in vitro.
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http://dx.doi.org/10.3892/ijmm.2016.2668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990324PMC
September 2016

Ghrelin ameliorates the human alveolar epithelial A549 cell apoptosis induced by lipopolysaccharide.

Biochem Biophys Res Commun 2016 05 19;474(1):83-90. Epub 2016 Apr 19.

Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China. Electronic address:

Ghrelin is a gastric acyl-peptide that plays an inhibitory role in cell apoptosis. Herein we investigate the protective effects of ghrelin in LPS-induced apoptosis of human alveolar epithelial A549 cells, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of A549 cells significantly in concentration- and time-dependent manners embodied in increased Bax and cleaved caspase-3 production, coupled with decreased Bcl-2 levels. Simultaneously, LPS remarkably decreased the expression of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinas (ERK) in A549 cells. However, ghrelin'pretreatment ameliorated LPS-caused alterations in the ratio of Bax/Bcl-2 and cleaved caspase-3 expression, whereas activated the PI3K/Akt and ERK signaling. These results demonstrate that ghrelin lightens LPS-induced apoptosis of human alveolar epithelial cells partly through activating the PI3K/Akt and ERK pathway and thereby might benefit alleviating septic ALI.
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http://dx.doi.org/10.1016/j.bbrc.2016.04.074DOI Listing
May 2016

Efficacy and Safety of Radiofrequency Ablation Combined with Transcatheter Arterial Chemoembolization for Hepatocellular Carcinomas Compared with Radiofrequency Ablation Alone: A Time-to-Event Meta-Analysis.

Korean J Radiol 2016 Jan-Feb;17(1):93-102. Epub 2016 Jan 6.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, China.

Objective: To compare the efficacy and safety of combined radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) with RFA alone for hepatocellular carcinomas (HCC).

Materials And Methods: Randomized controlled trial (RCT) studies that compared the clinical or oncologic outcomes of combination therapy of TACE and RFA versus RFA for the treatment of HCC were identified through literature searches of electronic databases (Pubmed, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure, and Google Scholar). Hazard ratios (HRs) or odds ratios (ORs) with their corresponding 95% confidence interval (CI) were combined as the effective value to assess the summary effects. The strength of evidence was rated by the Grading of Recommendations Assessment, Development, and Evaluation system.

Results: Six RCTs with 534 patients were eligible for inclusion in this meta-analysis. The meta-analysis showed that the combination of TACE and RFA is associated with a significantly longer overall survival (HR = 0.62, 95% CI: 0.49-0.78, p < 0.001) and recurrence-free survival (HR = 0.55, 95% CI: 0.40-0.76, p < 0.001) in contrast with RFA monotherapy. The seemingly higher incidence of major complications in the combination group compared with RFA group did not reach statistical significance (OR = 1.17, 95% CI: 0.39-3.55, p = 0.78).

Conclusion: In patients with HCC, the combination of TACE and RFA is associated with significantly higher overall survival and recurrence-free survival, as compared with RFA monotherapy, without significant difference in major complications.
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http://dx.doi.org/10.3348/kjr.2016.17.1.93DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720818PMC
September 2016

miR-488 acts as a tumor suppressor gene in gastric cancer.

Tumour Biol 2016 Jul 6;37(7):8691-8. Epub 2016 Jan 6.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.

MicroRNAs (miRNAs) are small, non-coding RNAs that modulate development, cell proliferation, and apoptosis. The deregulated expression of microRNAs is found in carcinogenesis including gastric cancer (GC). In this study, we showed that the expression levels of miR-488 were downregulated in GC tissues compared to in non-tumor tissues. In addition, the expression of miR-488 was also lower in GC cell lines in contrast with the gastric epithelial cell line (GES). In addition, the expression level of miR-488 was negatively correlated with the TNM stage in GC patients, and lower miR-488 expression was found in tumors with advanced TNM stage. The ectopic expression of miR-488 suppressed the GC cell proliferation, cell cycle, colony information, and migration. PAX6 was identified as a direct target gene of miR-488 in HGC-27. Moreover, we found that the expression level of PAX6 was upregulated in the GC tissues compared with the non-tumor tissues. The PAX6 expression level was correlated with the cancer TNM stage, and higher PAX6 expression was found in tumors with advanced TNM stage. Furthermore, there was an inverse correlation between PAX6 and miR-488 expression levels in GC tissues. Therefore, these studies demonstrated that miR-488 might act as a tumor suppressor miRNA in the development of GC.
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http://dx.doi.org/10.1007/s13277-015-4645-yDOI Listing
July 2016

TQ inhibits hepatocellular carcinoma growth in vitro and in vivo via repression of Notch signaling.

Oncotarget 2015 Oct;6(32):32610-21

Department of Gastroenterology, the First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Thymoquinone (TQ) has been reported to possess anti-tumor activity in various types of cancer. However, its effects and molecular mechanism of action in hepatocellular carcinoma (HCC) are still not completely understood. We observed that TQ inhibited tumor cell growth in vitro, where treatment with TQ arrested the cell cycle in G1 by upregulating p21 and downregulating cyclinD1 and CDK2 expression; moreover, TQ induced apoptosis by decreasing expression of Bcl-2 and increasing expression of Bax. Simultaneously, TQ demonstrated a suppressive impact on the Notch pathway, where overexpression of NICD1 reversed the inhibitory effect of TQ on cell proliferation, thereby attenuating the repressive effects of TQ on the Notch pathway, cyclinD1, CDK2 and Bcl-2, and also diminishing upregulation of p21 and Bax. In a xenograft model, TQ inhibited HCC growth in nude mice; this inhibitory effect in vivo, as well as of HCC cell growth in vitro, was associated with a discernible decline in NICD1 and Bcl-2 levels and a dramatic rise in p21 expression. In conclusion, TQ inhibits HCC cell growth by inducing cell cycle arrest and apoptosis, achieving these effects by repression of the Notch signaling pathway, suggesting that TQ represents a potential preventive or therapeutic agent in HCC patients.
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http://dx.doi.org/10.18632/oncotarget.5362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741716PMC
October 2015

Saikosaponin‑d suppresses the expression of cyclooxygenase‑2 through the phospho‑signal transducer and activator of transcription 3/hypoxia‑inducible factor‑1α pathway in hepatocellular carcinoma cells.

Mol Med Rep 2014 Nov 16;10(5):2556-62. Epub 2014 Sep 16.

Department of Public Health, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and accounts for ~6% of all types of human cancer worldwide, particularly in Asia. The incidence and mortality rates in the USA have also rapidly increased. Saikosaponin‑d (SSD), a saponin derivative extracted from several species of Bupleurum (Umbelliferae), possesses unique biological activities, including anti‑inflammatory, antihepatitic and immunomodulatory effects. Our previous studies have demonstrated that SSD inhibits the proliferation and induces the apoptosis of HCC SMMC‑7721 cells by downregulating the expression of cyclooxygenase (COX)‑2 and decreasing the production of prostaglandin E2. However, the specific mechanism underlying how SSD controls the expression of COX‑2 remains to be elucidated. In the present study, it was demonstrated that hypoxia inducible factor‑1α (HIF‑1α) was responsible for the expression of COX‑2 under hypoxic conditions in HCC cells, and the activation of signal transducer and activator of transcription 3 (STAT3) was required for the expression of HIF‑1α. SSD treatment inhibited STAT3 activation [phosphorylation of STAT3 (p‑STAT3)], reduced the protein level of HIF‑1α and decreased the expression of COX‑2. These results suggested that SSD may target HCC cells by suppressing the expression of COX‑2 through the p‑STAT3/HIF‑1α pathway.
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http://dx.doi.org/10.3892/mmr.2014.2574DOI Listing
November 2014

MicroRNA-106a targets TIMP2 to regulate invasion and metastasis of gastric cancer.

FEBS Lett 2014 Feb 17;588(4):600-7. Epub 2014 Jan 17.

Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Rood, Xi'an, Shanxi 710061, People's Republic of China.

Emerging evidence has shown that microRNA plays an important role in tumor development and progression. Here, we report that miR-106a is frequently up-regulated in gastric cancer tissues and positively correlates with metastasis. Restrained expression of miR-106a in gastric cancer cells significantly reduces their capacity of proliferation, migration and invasion. In tissue sections, the positive signal of miR-106a localized in metastasis-associated regions confirmed this result. Moreover, we show that TIMP2 is a direct downstream target for miR-106a and knockdown of TIMP2 strengthens the beneficial effects of miR-106a. Our study adds miR-106a to the complex mechanisms of tumor metastasis.
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http://dx.doi.org/10.1016/j.febslet.2013.12.028DOI Listing
February 2014

Overexpression of CENP-H as a novel prognostic biomarker for human hepatocellular carcinoma progression and patient survival.

Oncol Rep 2013 Nov 20;30(5):2238-44. Epub 2013 Aug 20.

Department of Gastroenterology, First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Centromere protein H (CENP-H) has been shown to be significantly upregulated in many types of cancers and is associated with disrupted cell cycle regulation, cell proliferation and genetic instability. The aim of the present study was to explore the expression and localization of CENP-H in hepatocellular carcinoma (HCC) and determine whether its overexpression is a prognostic biomarker for HCC. Reverse transcription-polymerase chain reaction (pcr), real-time qPCR and western blotting were used to compare CENP-H expression at the mRNA and protein levels in HCC samples and corresponding adjacent non-cancerous samples. CENP-H protein levels were determined in 60 paired paraffin-embedded HCC tissues using immunohistochemistry (IHC), and the correlation with clinicopathological features and patient prognosis was analyzed. In addition, an immunofluorescence assay was performed to test the expression and localization of CENP-H protein in HCC cells. Results showed that levels of CENP-H mRNA and protein were higher in HCC samples than in the corresponding adjacent non-cancerous samples. In 60 paired paraffin-embedded tissues, CENP-H was upregulated in the HCC samples (38/60, 63.3%) relative to the adjacent non-cancerous samples (21/60, 35%, P=0.003), and a higher level of upregulation was associated with tumor size (P=0.032); higher histological grade (P=0.001); more advanced TNM stage (P=0.002) and Chinese clinical stage (P=0.008); and poorer prognosis. In addition, consistent with the results of IHC, the immunofluorescence assay showed that CENP-H was localized in the nucleus of Hep3B cells. CENP-H was overexpressed in HCC, and its level of upregulation was an independent prognostic indicator, suggesting that CENP-H may be an effective therapeutic strategy for the treatment of HCC.
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http://dx.doi.org/10.3892/or.2013.2675DOI Listing
November 2013

α-Mangostin suppresses lipopolysaccharide-induced invasion by inhibiting matrix metalloproteinase-2/9 and increasing E-cadherin expression through extracellular signal-regulated kinase signaling in pancreatic cancer cells.

Oncol Lett 2013 Jun 4;5(6):1958-1964. Epub 2013 Apr 4.

Department of General Surgery, The Affiliated Hospital of Yan'an University, Yan'an, Shaanxi 716000;

Invasion and metastasis are major factors in the poor prognosis of pancreatic cancer, which remains one of the most aggressive and lethal diseases worldwide. α-mangostin, a major xanthone compound identified in the pericarp of mangosteen (, Linn; GML), possesses unique biological activities, including antioxidant, antitumor and anti-inflammatory effects. Whether α-mangostin is able to inhibit the invasive ability of pancreatic cancer cells has not been elucidated. In the present study, α-mangostin was shown to inhibit the invasive ability of the pancreatic cancer cell lines MIAPaCa-2 and BxPC-3. The results showed that α-mangostin inhibited the growth of the pancreatic cancer cells in a dose- and time-dependent manner. At concentrations of <5 M, α-mangostin had no significant effects on cytotoxicity, but significantly inhibited the invasion and migration of pancreatic cancer cells and the expression of matrix metalloproteinase (MMP)-2 and MMP-9, while increasing the expression of E-cadherin. The present data also showed that α-mangostin exerted an inhibitory effect on the phosphorylation of extracellular-signal-regulated kinase (ERK). Furthermore, the reduction of ERK phosphorylation by small interfering RNA (siRNA) potentiated the effect of α-mangostin. Taken together, the data suggest that α-mangostin inhibited the invasion and metastasis of pancreatic cancer cells by reducing MMP-2 and MMP-9 expression, increasing E-cadherin expression and suppressing the ERK signaling pathway. The present study suggests that α-mangostin may be a promising agent against pancreatic cancer.
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http://dx.doi.org/10.3892/ol.2013.1290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700960PMC
June 2013