Circulating tumor cell-derived exosome-transmitted long non-coding RNA TTN-AS1 can promote the proliferation and migration of cholangiocarcinoma cells.

BACKGROUND: Exosomes assume a pivotal role as essential mediators of intercellular communication within tumor microenvironments. Within this context, long noncoding RNAs (LncRNAs) have been observed to be preferentially sorted into exosomes, thus exerting regulatory control over the initiation and progression of cancer through diverse mechanisms. RESULTS: Exosomes were successfully isolated from cholangiocarcinoma (CCA) CTCs organoid and healthy human serum. Notably, the LncRNA titin-antisense RNA1 (TTN-AS1) exhibited a conspicuous up-regulation within CCA CTCs organoid derived exosomes. Furthermore, a significant elevation of TTN-AS1 expression was observed in tumor tissues, as well as in blood and serum exosomes from patients afflicted with CCA. Importantly, this hightened TTN-AS1 expression in serum exosomes of CCA patients manifested a strong correlation with both lymph node metastasis and TNM staging. Remarkably, both CCA CTCs organoid-derived exosomes and CCA cells-derived exosomes featuring pronounced TTN-AS1 expression demonstrated the capability to the proliferation and migratory potential of CCA cells. Validation of these outcomes was conducted in vivo experiments. CONCLUSIONS: In conclusion, our study elucidating that CCA CTCs-derived exosomes possess the capacity to bolster the metastasis tendencies of CCA cells by transporting TTN-AS1. These observations underscore the potential of TTN-AS1 within CTCs-derived exosomes to serve as a promising biomarker for the diagnosis and therapeutic management of CCA.

The learning curve for laparoscopic pancreaticoduodenectomy by a proficient laparoscopic surgeon: a retrospective study at a single center.

BACKGROUND: To explore the learning curve of single center laparoscopic pancreaticoduodenectomy (LPD) and evaluate the safety and efficacy of the operation at different stages. METHODS: A detailed review was conducted on the clinical data of 120 cases of laparoscopic pancreatoduodenectomy performed by the same surgeon between June 2018 and June 2022. Cases that did not provide insights into the learning curve of the procedure were excluded. The cumulative sum (CUSUM) analysis and the best fitting curve methods were employed to delineate the learning curve based on operation time and intraoperative blood loss. The study further evaluated the number of surgeries required to traverse the learning curve. Outcome measures, including operation time, intraoperative blood loss, length of stay, complications, and other relevant indicators, were extracted and compared across different phases of the learning curve. RESULT: The maximum turning point of the fitting curve was found in 35 cases by the cumulative sum method of operation time, after which the learning curve could be considered to have passed. The fitting curve obtained by the cumulative sum method of intraoperative blood loss was stable in 30 cases and proficient in 60 cases, which was basically consistent with the fitting curve of operation time. Taking 35 cases as the boundary, the learning curve is divided into learning improvement stage and mastering stage. There was no statistical significance in the general data of the two stage patients (P > 0.05). Hospitalization days decreased from 19 to 15 days (P < 0.05);Pancreatic fistula decreased from 20.0% of grade B and 8.6% of grade C to 7.1% of grade B and 3.5% of grade C (P < 0.05), and the operative time decreased from (376.9 ± 48.2) minutes to (294.4 ± 18.7) minutes (P < 0.05). Intraoperative blood loss decreased from 375 to 241 ml (P < 0.05). CONCLUSION: Thirty-five patients with LPD can reach the proficiency stage and the perioperative indexes can be improved.

Characteristics of phenotypic antibiotic resistance of Helicobacter pylori and its correlation with genotypic antibiotic resistance: A retrospective study in Ningxia.

BACKGROUND: Geographic differences exist in the antibiotic resistance patterns of Helicobacter pylori. Personalized treatment regimens based on local or individual resistance data are essential. We evaluated the current status of H. pylori resistance in Ningxia, analyzed resistance-related factors, and assessed the concordance of phenotypic and genotypic resistance. METHODS: Strains were isolated from the gastric mucosa of patients infected with H. pylori in Ningxia and relevant clinical information was collected. Phenotypic antibiotic susceptibility assays (Kirby-Bauer disk diffusion) and antibiotic resistance gene detection (Sanger sequencing) were performed. RESULTS: We isolated 1955 H. pylori strains. The resistance rates of H. pylori to amoxicillin, levofloxacin, clarithromycin, and metronidazole were 0.9%, 42.4%, 40.4%, and 94.2%, respectively. Only five tetracycline-resistant and one furazolidone-resistant strain were identified. Overall, 3.3% of the strains were sensitive to all six antibiotics. Multidrug-resistant strains accounted for 22.9%, of which less than 20% were from Wuzhong. Strains isolated from women and patients with nonulcerative disease had higher rates of resistance to levofloxacin and clarithromycin. Higher rates of resistance to metronidazole, levofloxacin, and clarithromycin were observed in the older age group than in the younger age group. The kappa coefficients of phenotypic resistance and genotypic resistance for levofloxacin and clarithromycin were 0.830 and 0.809, respectively, whereas the remaining antibiotics showed poor agreement. CONCLUSION: H. pylori antibiotic resistance is severe in Ningxia. Therefore, furazolidone, amoxicillin, and tetracycline are better choices for the empirical therapy of H. pylori infection in this region. Host sex, age, and the presence of ulcerative diseases may affect antibiotic resistance of the bacteria. Personalized therapy based on genetic testing for levofloxacin and clarithromycin resistance may be a future direction for the eradication therapy of H. pylori infection in Ningxia.

Short-term clinical outcomes of laparoscopic duodenum-preserving pancreatic head resection for the management of pancreatic-head cystic neoplasms.

BACKGROUND: In this study, we aimed to investigate the short-term clinical outcomes of laparoscopic duodenum-preserving pancreatic-head resection (LDPPHR) for the management of pancreatic-head cystic neoplasms. METHODS: This retrospective study included 60 patients who were treated with pancreatic-head cystic neoplasms at the Shandong Provincial Hospital Affiliated to Shandong First Medical University from December 2019 to July 2022. RESULTS: No significant difference was found between the two groups in terms of the baseline and pathological characteristics of patients (P > 0.05). The postoperative exhaust time was shorter in the LDPPHR group compared with the laparoscopic pancreaticoduodenectomy (LPD) group (2 (2 and 4) vs. 4 (3 and 5) days; P = 0.003). No significant difference was found between the two groups in terms of operative time, estimated blood loss, intraoperative transfusion, hemoglobin levels on the first postoperative day, total bilirubin before discharge, direct bilirubin before discharge, postoperative hospital stay, postoperative pancreatic fistula, bile leakage, hemorrhage, peritoneal effusion, abdominal infection, delayed gastric emptying, interventional embolization hemostasis, reoperation, and 30-day readmission (P > 0.05). No conversion and 90-day mortality were found in the two groups. The LDPPHR group showed a higher 3-month postoperative PNI, 6-month postoperative TG and 6-month postoperative BMI than the LPD group (P < 0.05). CONCLUSIONS: Compared with LPD, LDPPHR can decrease the postoperative exhaust time of patients, improve the short-term postoperative nutritional status, and does not decrease the safety of the perioperative period.

Benchmark for establishment of organoids from gastrointestinal epithelium and cancer based on available consumables and reagents.

Gastrointestinal cancers are a public health problem that threatens the lives of human being. A good experimental model is a powerful tool to promote the uncovering pathogenesis and establish novel treatment methods. High-quality biomedical research requires experimental models to recapitulate the physiological and pathological states of their parental tissues as much as possible. Organoids are such experimental models. Organoids refer to small organ-like cellular clusters formed by the expansion and passaging of living tissues in 3D culture medium in vitro. Organoids are highly similar to the original tissues in terms of cellular composition, cell functions, and genomic profiling. Organoids have many advantages, such as short preparation cycles, long-term storage based on cryopreservation, and reusability. In recent years, researchers carried out the establishment of organoids from gastrointestinal mucosa and cancer tissues, and accumulated valuable experiences. In order to promote effective usage and further development of organoid-related technologies in the research of gastrointestinal diseases, this study proposes a benchmark based on utilization of available experimental consumables and reagents, which are involved in the key steps such as collection and pretreatment of biospecimen, organoid construction, organoid cryopreservation and recovery, growth status evaluation, and organoid quality control. We believe that the standard for the construction and preservation of organoids derived from human gastrointestinal epithelium and cancer tissues can provide an important reference for the majority of scientific researchers.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

CDK1-mediated BCL9 phosphorylation inhibits clathrin to promote mitotic Wnt signalling.

Uncontrolled cell division is a hallmark of cancer. Deregulation of Wnt components has been linked to aberrant cell division by multiple mechanisms, including Wnt-mediated stabilisation of proteins signalling, which was notably observed in mitosis. Analysis of Wnt components revealed an unexpected role of B-cell CLL/lymphoma 9 (BCL9) in maintaining mitotic Wnt signalling to promote precise cell division and growth of cancer cell. Mitotic interactome analysis revealed a mechanistic role of BCL9 in inhibiting clathrin-mediated degradation of LRP6 signalosome components by interacting with clathrin and the components in Wnt destruction complex; this function was further controlled by CDK1-driven phosphorylation of BCL9 N-terminal, especially T172. Interestingly, T172 phosphorylation was correlated with cancer patient prognosis and enriched in tumours. Thus, our results revealed a novel role of BCL9 in controlling mitotic Wnt signalling to promote cell division and growth.

Potential prognosis index for m6A-related mRNA in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CHOL) is a malignant tumor that originates in the extrahepatic bile duct and can extend from the hilar region to the lower end of the common bile duct. The prognosis of CHOL patients is particularly poor; therefore, in this study, we screened mRNAs correlated with N6-methyladenosine (m6A) to construct a risk model for prognosis in CHOL. METHODS: The TCGA-CHOL dataset was applied to obtain and analyze the coexpression of 1281 m6A-related mRNAs, from which 14 were selected for further analysis through univariate proportional hazards (cox) regression analysis. Aryl hydrocarbon receptor interacting protein (AIP), CCAAT/enhancer binding protein beta (CEBPB), syndecan1 (SDC1), vacuolar protein sorting 25 homolog (VPS25) and syntaxin binding protein 2 (STXBP2) were then screened out through the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis to develop a precise m6A-related mRNA prognosis risk model (MRMRPM) with an area under curve (AUC) of 0.908 and 0.923 after 1 and 2 years, respectively. We divided the samples into high-risk and low-risk groups using the m6A-related mRNA prognosis risk model. RESULTS: Kaplan-Meier analysis indicated poor overall survival (OS) for the high-risk group. Two Gene Expression Omnibus (GEO) datasets (GSE89748 and GSE107943) were used to validate the risk model. The results of drug sensitivity and immune cell infiltration analysis showed that the risk model could serve as a prognosis index of potential immunotherapeutic characteristics and drug sensitivity. Furthermore, the proportion of resting dendritic cells and regulatory T cells was positively associated with an increased expression of four m6A-related mRNAs - AIP, CEBPB, SDC1, and VPS25 - in the high-risk CHOL group. CONCLUSIONS: Our findings suggest that this model can be a prognostic indicator for CHOL patients.

Purpurin binding interacts with LHPP protein that inhibits PI3K/AKT phosphorylation and induces apoptosis in colon cancer cells HCT-116.

Colorectal cancer (CRC) is the leading type of diagnosed cancer; globally, it resides in the fourth-leading origin of cancer-interrelated mortality in the globe. The treatment strategies were chemotherapy and potent radiotherapy. Although chemotherapy treatment can eliminate tumor cells, it remains with unnecessary toxic effects in cancer patients. Therefore, the identification of natural-based compounds, which have selectively inhibiting target proteins with limited toxicity that can facilitate the therapeutic approaches against CRC. In this existing approach, which highlights the binding efficacy of our anthraquinone compound, purpurin against phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) protein restrains the CRC cell growth by inhibiting phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT), cell proliferation, and inducing apoptosis signaling. Primarily, purpurin (36 µM) exposed to HCT-116 cells and incubated for 24 and 48 h could induce reactive oxygen species production, subsequently alter mitochondrion membrane, and increase the apoptotic cells in HCT-116. LHPP, a kind of histidine phosphatase protein, has been considered as a tumor suppressor in numerous carcinomas. However, purpurin-mediated LHPP proteins and its associated molecular events in CRC remain unclear. In our docking studies revealed that purpurin has been strongly interacts with LHPP via hydrophobic and hydrophilic binding interaction. Western blot results confirmed that purpurin enhances the expression of LHPP protein, thereby inhibits the expression of phosphorylated-PI3K/AKT, EGFR, cyclin-D1, PCNA in HCT-116 cells. Moreover, purpurin induces messenger RNA expression of apoptotic genes (Bax, CASP-9, and CASP-3) in HCT-116 cells. Thus, we conclude that purpurin could be a natural and useful compound, which inhibits the growth of CRC cells through the activation of LHPP proteins.

Comparison of clinical outcomes between enucleation and regular pancreatectomy in patients with non-functional pancreatic neuroendocrine tumors: a retrospective multicenter and propensity score-matched study.

OBJECTIVE: There are limited data from retrospective studies on whether therapeutic outcomes after regular pancreatectomy are superior to those after enucleation in patients with small, peripheral and well-differentiated non-functional pancreatic neuroendocrine tumors. This study aimed to compare the short- and long-term outcomes of regular pancreatectomy and enucleation in patients with non-functional pancreatic neuroendocrine tumors. METHODS: Between January 2007 and July 2020, 227 patients with non-functional pancreatic neuroendocrine tumors who underwent either enucleation (n = 89) or regular pancreatectomy (n = 138) were included. Perioperative complications, disease-free survival, and overall survival probabilities were compared. Propensity score matching was performed to balance the baseline differences between the two groups. RESULTS: The median follow-up period was 60.76 months in the enucleation group and 43.29 months in the regular pancreatectomy group. In total, 34 paired patients were identified after propensity score matching. The average operative duration in the enucleation group was significantly shorter than that in the regular pancreatectomy group (147.94 ± 42.39 min versus 217.94 ± 74.60 min, P < 0.001), and the estimated blood loss was also significantly lesser (P < 0.001). The matched patients who underwent enucleation displayed a similar overall incidence of postoperative complications (P = 0.765), and a comparable length of hospital stay (11.12 ± 3.90 days versus 9.94 ± 2.62 days, P = 0.084) compared with those who underwent regular pancreatectomy. There were no statistically significant differences between the two groups in disease-free survival and overall survival after propensity score matching. CONCLUSION: Enucleation in patients with non-functional pancreatic neuroendocrine tumors was associated with shorter operative time, lesser intraoperative bleeding, similar overall morbidity of postoperative complications, and comparable 5-year disease-free survival and overall survival when compared with regular pancreatectomy.

Hypoxia-induced modulation of glucose transporter expression impacts 18F-fluorodeoxyglucose PET-CT imaging in hepatocellular carcinoma.

PURPOSE: To investigate the molecular mechanisms underlying the variable standard uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging in hepatocellular carcinoma (HCC) and whether hypoxia-induced glucose transporter expression contributes to the progression of HCC and the rate of glycolysis in HCC cells. MATERIALS AND METHODS: Sixteen HCC specimens obtained from patients who underwent pre-treatment staging with 18F-FDG PET-CT imaging were divided into high maximum SUV (SUVmax > 8) and low SUVmax (SUVmax < 5) groups and employed for whole-genome gene expression profiling using GeneChip Human Genome U133 Plus 2.0 Arrays. The relationship between SUVmax and the expression of glucose transporters 1 and 3 (GLUT1 and GLUT3) was further validated using immunohistochemical analysis. The expression of GLUT1 and GLUT3 in different HCC cells under hypoxia and normoxia conditions were monitored by quantitative reverse transcription PCR (RT-qPCR). Glycolysis and FDG uptake by HCC cells were measured using the Seahorse XF glycolysis stress test and 18F-FDG PET-CT imaging. The effect of GLUT1 and GLUT3 on glucose uptake in HCC cells was examined using the fluorescent D-glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) followed by detection of fluorescence produced by the cells using flow cytometry. RESULTS: Glucose transporters are differentially expressed between samples from HCC patients with high and low SUVmax. In particular, over-expression of GLUT1 and GLUT3 in high SUVmax patients was correlated with high glucose uptake and overall survival. The expression of GLUT1 and GLUT3 was significantly induced by hypoxia in different HCC cells. High expression of GLUT1 and GLUT3 in HCC cells were correlated with high rates of glycolysis and 18F-FDG uptake. Therefore, our data suggested that hypoxia-induced glucose transporters expression could result in the variations of 18F-FDG PET-CT imaging and progression of HCC, contributing to more aggressive disease phenotypes like large tumor size, recurrence, and poor survival. CONCLUSION: Over-expression of GLUT1 and GLUT3 significantly increase glucose uptake in HCC cells. Hypoxia-induced glucose transporters expression may therefore be a contributing variable in 18F-FDG PET-CT imaging and progression in HCC.

Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk.

The platelet-derived growth factor (PDGF) signaling pathway plays important roles in development and progression of human cancers. In our study, we aimed to identify genetic variants of the PDGF pathway genes associated with pancreatic cancer (PC) risk in European populations using three published genome-wide association study datasets, which consisted of 9,381 cases and 7,719 controls. The expression quantitative trait loci (eQTL) analysis was also performed using data from the 1000 Genomes, TCGA and GTEx projects. As a result, we identified two potential susceptibility loci (rs5757573 and rs6001516) of PDGFB associated with PC risk [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.05-1.16, and p = 4.70 × 10-5 for the rs5757573 C allele and 1.21, 1.11-1.32, and 2.01 × 10-5 for the rs6001516 T allele]. Haplotype analysis revealed that the C-T haplotype carriers had a significantly increased risk of PC than those carrying the T-C haplotype (OR = 1.23, 95% CI = 1.12-1.34, p =5.00 × 10-6 ). The multivariate regression model incorporating the number of unfavorable genotypes (NUGs) with age and sex showed that carriers with 1-2 NUGs, particularly among 60-70 age group or males, had an increased risk of PC, compared to those without NUG. Furthermore, the eQTL analysis revealed that both loci were correlated with a decreased mRNA expression level of PDGFB in lymphoblastoid cell lines and pancreatic tumor tissues (p = 0.015 and 0.071, respectively). Our results suggest that genetic variants in PDGFB may play a role in susceptibility to PC. Further population and functional validations of our findings are warranted.

miRNA-338-3p/CDK4 signaling pathway suppressed hepatic stellate cell activation and proliferation.

BACKGROUND: Activated hepatic stellate cell (HSC) is the main fibrogenic cell type in the injured liver. miRNA plays an important role in activation and proliferation of HSC. METHODS: Our previous study examined the expression profiles of microRNAs in quiescent and activated HSC. Real-time PCR and western blot were used to detect the expression of Collagen type I (Col 1) and Alpha-Smooth Muscle Actin (α-SMA). CCK-8 and Edu assay was used to measure the proliferation rate of HSC. Luciferase reporter gene assay was used to tested the binding between miR-338-3p and Cyclin-dependent kinase 4 (CDK4). RESULTS: We found overexpression of miR-338-3p could inhibit Col 1 and α-SMA, two major HSC activation markers, whereas miR-338-3p inhibitor could promote them. Besides, miR-338-3p overexpression could suppress the growth rate of HSC. Further, we found that CDK4, a pleiotropic signaling protein, was a direct target gene of miR-338-3p. Moreover, we found that overexpression of CDK4 could block the effects of miR-338-3p. CONCLUSIONS: We found miR-338-3p is an anti-fibrotic miRNA which inhibits cell activation and proliferation. Our findings suggest that miR-338-3p/CDK4 signaling pathway participates in the regulation of HSC activation and growth and may act as a novel target for further anti-fibrotic therapy.

[Quadruple regimens using domestically manufactured drugs in gastritis and duodenal ulcer patients for Helicobacter pylori eradication: a perspective, multicenter, randomized controlled trial].

OBJECTIVE: To observe the effects and safety of quadruple regimens including domestically manufactured rabeprazole used as first line/initial therapy for Helicobacter pylori(H.pylori) eradication in gastritis and duodenal ulcer patients, and to investigate the effects of extended use of bismuth after the quadruple therapy on eradication of H. pylori. METHODS: From January to August 2013, 430 patients with chronic gastritis or duodenal ulcer who were confirmed as H. pylori positive in gastroscopy for upper gastrointestinal symptoms were enrolled from 12 centers in China for initial treatment using quadruple regimens for H. pylori eradication. The study was a prospective, multicenter, randomized double-blinded double-dummy parallel-controlled clinical trial. The 310 chronic gastritis patients were divided into 2 groups: group A1 was given quadruple regime (rabeprazole+ amoxicillin+ clarithromycin+ bismuth potassium citrate) for 10 days followed by bismuth-placebo for 21 days; group A2 was given the quadruple regimen for 10 days and then bismuth potassium citrate for 21 days. The duodenal ulcer patients were given the quadruple for 10 days, then rabeprazole for 14 days. All the patients took (13)C urea breath test to detect H. pylori 28 days after medicine withdrawal. RESULTS: Altogether 428 cases were enrolled and 404 completed the trial. The total eradication rate in the chronic gastritis patients was 85.1% (262/308, intention-to-treat (ITT)analysis), which was 81.7% (125/153, ITT) in the A1 group and 88.4% (137/155, ITT) in the A2 group; the eradication rate in the duodenal ulcer patients was 85.8% (103/120, ITT). No severe adverse effects were reported. The symptoms (pain, burning sensation, reflux, belching, nausea, and vomiting) improvement status was similar among A1 and A2 groups. CONCLUSIONS: The quadruple regimen using rabeprazole manufactured in China and administered for 10 days as first line/initial therapy in chronic gastritis and duodenal ulcer patients could achieve good H. pylori eradication rate. The extended use of bismuth after 10-day quadruple regimen might further improve the eradication rate. The regimens containing proton-pump inhibitor and bismuth may be well tolerated and safe in clinical application.

EDIL3 is a novel regulator of epithelial-mesenchymal transition controlling early recurrence of hepatocellular carcinoma.

BACKGROUND & AIMS: Patients with advanced hepatocellular carcinoma (HCC) continue to have a dismal prognosis. Early recurrence, metastases and angiogenesis are the major obstacles to improve the outcome of HCC. Epithelial-mesenchymal transition (EMT) is a key contributor to cancer metastasis and recurrence, which are the major obstacles to improve prognosis of HCC. METHODS: Combining gene expression profiles of HCC samples with or without early recurrence and established cell lines with epithelial or mesenchymal phenotype, EDIL3 was identified as a novel regulator of EMT. The expression of EDIL3 was evaluated by quantitative PCR, Western blotting or immunohistochemistry. The effects of EDIL3 on the angiogenesis and metastasis of HCC cells were examined by wound healing, Matrigel invasion and tube formation assay in vitro and orthotopic xenograft mouse model of HCC in vivo. The signaling pathways of EDIL3 mediated were investigated through microarray and Western blotting analysis. RESULTS: EDIL3 was identified as a novel regulator of EMT, which contributes to angiogenesis, metastasis and recurrence of HCC. EDIL3 induces EMT and promotes HCC migration, invasion and angiogenesis in vitro. Mechanistically, overexpression of EDIL3, which was regulated by the downregulation of miR-137 in HCC, triggered the activation of ERK and TGF-ß signaling through interactions with αvß3 integrin. Blocking ERK and TGF-ß signaling overcomes EDIL3 induced angiogenesis and invasion. Using the orthotopic xenograft mouse model of HCC, we demonstrated that EDIL3 enhanced the tumorigenic, metastatic and angiogenesis potential of HCC in vivo. CONCLUSIONS: EDIL3-mediated activation of TGF-ß and ERK signaling could provide therapeutic implications for HCC.

Antiviral therapy in the improvement of survival of patients with hepatitis B virus-related hepatocellular carcinoma treated with sorafenib.

BACKGROUND AND AIM: To evaluate the role of antiviral therapy with nucleoside analogs (NAs) in sorafenib-treated patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: A retrospective cohort study was done in 151 HBV-related HCC patients treated with sorafenib at Sun Yat-sen University Cancer Center between 2007 and 2012. Overall survival (OS), progression-free survival and adverse events were compared in patients treated with/without NAs. Subgroup analysis and Cox regression analysis were performed to determine the efficiency of NAs and prognostic factors for OS. RESULTS: HBV-related HCC patients (n=151) were identified from our database of HCC patients treated with sorafenib. Patients treated with NAs (antiviral group, n=88) had significantly improved OS compared with the patients who received no NAs (non-antiviral group, n=63; median OS: 16.47 months vs 13.10 months, P=0.03). Patients in the antiviral group had a significant risk reduction of death compared with the non-antiviral group (hazard ratio: 0.67, 95% confidence interval: 0.46-0.98, P=0.04). By subgroup analysis, patients of Barcelona Clinic Liver Cancer (BCLC) stage C and patients with higher presorafenib HBV-DNA level achieved better survival improvement. Antiviral therapy with NAs was one of the independent prognostic factors for OS of HBV-related HCC patients who were treated with sorafenib. CONCLUSION: Antiviral therapy with NAs improved OS of HBV-related HCC patients treated with sorafenib, especially in patients with BCLC stage C disease and higher HBV-DNA level.

The characteristics of oesophageal squamous cell carcinoma: an analysis of 1317 cases in southeastern China.

AIM OF THE STUDY: To research the demographic and histopathological features of ESCC in southeastern China. MATERIAL AND METHODS: We retrospectively reviewed the ESCC cases in the biobank of the National Engineering Centre for Biochip in Shanghai, which cooperates with lots of hospitals and research institutions in southeastern China. The patients were pathologically confirmed as having ESCC. The demographic and histopathological features of these cases were analysed subsequently. RESULTS: A total of 1317 patients were enrolled. The overall male: female ratio was 2.88: 1. 74.34% of these cases occurred in people aged between 50-70 years. Dysphagia was the most common symptom, which accounted for 93.40% of all the patients. Stage II and III were predominant (79.73%). 72.89% of patients had a tumour length greater than 3 cm. Most of the tumours (65.83%) were located in middle third of the oesophagus. There was a significant difference among the tumour stage, length, and location in different sex groups (P < 0.05), but not between different age groups (P > 0.05). In males, ESCC is usually located in the lower parts, with a longer tumour length and higher tumour stage. 24.15% of patients had lymph nodes ratio (LNR) > 0.2. CONCLUSIONS: In our analysis, dysphagia was more common in ESCC patients, to whom more attention should be paid. Additionally, males had a higher incidence, with longer and more distant disease, which gives a poor prognosis.

A 4-gene panel as a marker at chromosome 8q in Asian gastric cancer patients.

A widely held viewpoint is that the use of multiple markers, combined in some type of algorithm, will be necessary to provide high enough discrimination between diseased cases and non-diseased. We applied stepwise logistic regression analysis to identify the best combination of the 32 biomarkers at chromosome 8q on an independent public microarray test set of 80 paired gastric samples. A combination of SULF1, INTS8, ATP6V1C1, and GPR172A was identified with a prediction accuracy of 98.0% for discriminating carcinomas from adjacent noncancerous tissues in our previous 25 paired samples. Interestingly, the overexpression of SULF1 was associated with tumor invasion and metastasis. Function prediction analysis revealed that the 4-marker panel was mainly associated with acidification of intracellular compartments. Taken together, we found a 4-gene panel that accurately discriminated gastric carcinomas from adjacent noncancerous tissues and these results had potential clinical significance in the early diagnosis and targeted treatment of gastric cancer.