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Gastric Cancer - Top 30 Publications

Endoscopic and histopathologic reflux-associated mucosal damage in the remnant esophagus following transthoracic esophagectomy for cancer-5-year long-term follow-up.

Gastroesophageal reflux is a common problem following esophagectomy and reconstruction with gastric interposition. Despite a routine prescription of proton pump inhibitors, reflux-associated mucosal damage in the remnant esophagus is frequently observed. Purpose of this study is to evaluate mucosal damage in the esophageal remnant during long-term follow-up and to compare the prevalence of this damage between the subgroups of esophageal squamous cell and adenocarcinoma. All patients undergoing transthoracic Ivor-Lewis esophagectomy were prospectively entered in our IRB approved database. All patients underwent a routine check-up program with yearly surveillance endoscopies following esophagectomy. Only patients with a complete follow-up were included into this study. Endoscopic and histopathologic mucosal changes of the remnant esophagus were analyzed in close intervals. A total of 50 patients met the inclusion criteria, consisting of 31 adenocarcinomas (AC) and 19 squamous cell carcinomas (SCC). Mucosal damage was already seen 1 year after surgery in 20 patients macroscopically (43%) and in 21 patients microscopically (45%). At 5-year follow-up the prevalence for macroscopic and microscopic damage was 55% and 60%, respectively. The prevalence of mucosal damage was higher in AC patients than in SCC patients (1y-FU: 51% [AC] vs. 28% [SCC]; 5y-FU: 68% [AC] vs. 35% [SCC], P < 0.05). Newly acquired Barrett's esophagus was seen in 10 patients (20%) with two of those patients (20%) showing histopathologic proof of neoplasia. This study shows a high prevalence of reflux-associated mucosal damage in the remnant esophagus one year out of surgery and only a moderate increase in prevalence in the following years. Mucosal damage was more frequently seen in AC patients and the occurrence of de-novo Barrett's esophagus and de-novo neoplasia was high. Endoscopic surveillance with targeted biopsies seems to be an indispensable tool to follow patients after esophagectomy appropriately.

A selective sphingosine-1-phosphate receptor 1 agonist SEW-2871 aggravates gastric cancer by recruiting myeloid-derived suppressor cells.

The immune status of tumor microenvironment in gastric cancer is poorly understood, which limits the development of novel strategies in this field. Sphingosine-1-phosphate (S1P) acts as an immune modulator, but the role of S1P in gastric cancer is elusive. Here, we aim to investigate S1P receptor 1 (S1P1)-mediated effect of S1P in gastric cancer. We generated a xenograft mouse model and used SEW-2871, a S1P1 specific agonist to activate S1P1 signaling. Tumor-infiltrating lymphocytes (TILs) were isolated and analyzed using flow cytometry. Chemokine expression of tumor cells was evaluated using quantitative real-time polymerase chain reaction. Myeloid-derived suppressor cells (MDSCs) migration was assessed using Transwell chambers. SEW-2871 promoted tumor growth in our mouse model, and induced a higher level of MDSC and a reduced level of CD8+CD69+ T cells within tumor. Consistently, the anti-tumoral function of cytotoxic T lymphocytes was impaired in mice with SEW-2871 treatment. Additionally, SEW-2871 enhanced expression of several MDSC recruitment-associated chemokines (CXCL12, CXCL5 and CCL2) in tumor cells. These chemokines facilitated MDSC migration by interaction with CCR2, CXCR2 and CXCR4. S1P1 signaling promoted gastric cancer by enhancing chemokine expression in tumor cells and recruiting MDSC to tumor microenvironment, which impaired anti-tumoral function of TILs.

Immature colon carcinoma transcript-1 promotes proliferation of gastric cancer cells.

Gastric cancer is the fourth most common malignant tumor and has been considered as one of the leading causes of cancer-related death worldwide. The identification of the molecular mechanism during gastric cancer progression is urgently needed, which will help to develop more effective treatment strategies. As a component of the human mitoribosome, immature colon carcinoma transcript-1 (ICT1) might be involved in tumor formation and progression. However, its biological function and the corresponding mechanism in gastric cancer have been poorly characterized. To study the mechanism of ICT1 in gastric cancer, we first investigated the mRNA levels of ICT1 in human normal and gastric cancer tissues using datasets from the publicly available Oncomine database. The results showed that ICT1 is overexpressed in gastric cancer tissues. Then in order to study the role of ICT1 in gastric cancer, two shRNAs were used to silence ICT1 in MGC80-3 and AGS cells. Functional analysis showed ICT1 knockdown significantly inhibited the proliferation of gastric cancer cells and induced apoptosis. Further, mechanistic study demonstrated that ICT1 silencing induced cell-cycle arrest at G2/M phase via the suppression of cyclin A2 and cyclin B1. In addition, ICT1 silencing also increased cleaved caspase-3 and activated PARP in gastric cancer cells. These findings suggest that ICT1 may play a crucial role in promoting gastric cancer proliferation in vitro.

MiR-129 inhibits cell proliferation and metastasis by targeting ETS1 via PI3K/AKT/mTOR pathway in prostate cancer.

New evidence suggests that microRNAs (miRNAs) play an important role in regulating the development and progression of prostate cancer. However, their specific functions and mechanisms remained to be further explored. MiR-129 has been reported in gastric cancers, colon cancer and lung cancer. In this study, we disclosed a new tumor suppresser function of miR-129 in prostate cancer. The purpose of our study is to clarify the effects of miR-129 in cellular processes correlated with cancer development and progression of prostate cancer cell by regulating ETS1. MiR-129 and ETS1 expression in prostate cancer tissues, tumor adjacent tissues and cells were tested by quantitative real-time PCR. We validated the target relationship between miR-129 and ETS1 by dual luciferase reporter gene system. MTT, colony formation, tumorigenesis assays, flow cytometry, wound healing and transwell assays were used to analyze cell viability, proliferation, migration, and invasiveness in vivo and in vitro. The level of ETS1 protein expression was detected by western blot. Here we demonstrate that miR-129 have a relatively reduced expression in prostate cancer cell lines and tissues. Morever, the miR-129 inhibits the expression of ETS1 by binding its 3'-UTR. The overexpression of miR-129 can inhibit PC-3 cell viability, proliferation, migration and invasion through targeting ETS1 by PI3K/AKT/mTOR signaling pathway. These findings suggested that miR-129 could directly suppress ETS1, which might be one of potential mechanisms in inhibiting cell processes including viability, proliferation, migration and invasiveness of prostate cancercells and it provides new clues for us to understand the carcinogenesis of prostate cancer. In addition, it may help to develop a treatment approach for ETS1-activated prostate cancer.

Opa-interacting protein 5 modulates docetaxel-induced cell death via regulation of mitophagy in gastric cancer.

Damage to mitochondria induces mitophagy, a cellular process that is gaining interest for its therapeutic relevance to a variety of human diseases. However, the mechanism underlying mitochondrial depolarization and clearance in mitophagy remains poorly understood. We previously reported that mitochondria-induced cell death was caused by knockdown of Neisseria gonorrhoeae opacity-associated-interacting protein 5 in gastric cancer. In this study, we show that Neisseria gonorrhoeae opacity-associated-interacting protein 5 loss and gain of function modulates mitophagy induced by treatment with docetaxel, a chemotherapy drug for gastric cancer. The activation of mitophagy by Neisseria gonorrhoeae opacity-associated-interacting protein 5 overexpression promoted cell survival, preventing docetaxel-induced mitochondrial clearance. Conversely, short interfering RNA-mediated knockdown of Neisseria gonorrhoeae opacity-associated-interacting protein 5 accelerated docetaxel-induced apoptosis while increasing mitochondrial depolarization, reactive oxygen species, and endoplasmic reticulum stress and decreasing adenosine triphosphate production. We also found that the mitochondrial outer membrane proteins mitofusin 2 and phosphatase and tensin homolog-induced putative kinase 1 colocalized with Neisseria gonorrhoeae opacity-associated-interacting protein 5 in mitochondria and that mitofusin 2 knockdown altered Neisseria gonorrhoeae opacity-associated-interacting protein 5 expression. These findings indicate that Neisseria gonorrhoeae opacity-associated-interacting protein 5 modulates docetaxel-induced mitophagic cell death and therefore suggest that this protein comprises a potential therapeutic target for gastric cancer treatment.

Genome-wide analysis of Epstein-Barr virus identifies variants and genes associated with gastric carcinoma and population structure.

Epstein-Barr virus is a ubiquitous virus and is associated with several human malignances, including the significant subset of gastric carcinoma, Epstein-Barr virus-associated gastric carcinoma. Some Epstein-Barr virus-associated diseases are uniquely prevalent in populations with different geographic origins. However, the features of the disease and geographically associated Epstein-Barr virus genetic variation as well as the roles that the variation plays in carcinogenesis and evolution remain unclear. Therefore, in this study, we sequenced 95 geographically distinct Epstein-Barr virus isolates from Epstein-Barr virus-associated gastric carcinoma biopsies and saliva of healthy donors to detect variants and genes associated with gastric carcinoma and population structure from a genome-wide spectrum. We demonstrated that Epstein-Barr virus revealed the population structure between North China and South China. In addition, we observed population stratification between Epstein-Barr virus strains from gastric carcinoma and healthy controls, indicating that certain Epstein-Barr virus subtypes are associated with different gastric carcinoma risks. We identified that the BRLF1, BBRF3, and BBLF2/BBLF3 genes had significant associations with gastric carcinoma. LMP1 and BNLF2a genes were strongly geographically associated genes in Epstein-Barr virus. Our study provides insights into the genetic basis of oncogenic Epstein-Barr virus for gastric carcinoma, and the genetic variants associated with gastric carcinoma can serve as biomarkers for oncogenic Epstein-Barr virus.

PD-L1 expression is mainly regulated by IFN-γ associated with JAK-STAT pathway in gastric cancer.

Despite multidisciplinary treatment for patients with advanced gastric cancer, their prognosis still remains poor. Therefore, the development of novel therapeutic strategies is urgently needed, and immunotherapy utilizing anti-programmed death 1/-programmed death ligand-1 mAb is an attractive approach. However, as there is limited information on how programmed death ligand-1 is upregulated on tumor cells within the tumor microenvironment, we examined the mechanism of programmed death ligand-1 regulation with a particular focus on interferon gamma in in-vitro setting and in clinical samples. Our in-vitro findings showed interferon gamma upregulated programmed death ligand-1 expression on solid tumor cells through the JAK-signal transducer and activator of transcription pathway, and impaired the cytotoxicity of tumor antigen-specific CTL against tumor cells. Treatment of cells with anti-programmed death ligand-1 mAb after interferon gamma-pre-treatment, the reduced anti-tumor CTL activity by interferon gamma reached a higher level than the non-treatment control targets. On the other hand, programmed death ligand-1 expression on tumor cells also significantly correlated with epithelial-mesenchymal transition phenotype in a panel of solid tumor cells. In clinical gastric cancer samples, tumor membrane programmed death ligand-1 expression significantly positively correlated with the presence of CD8-positive T cells in the stroma and interferon gamma expression in the tumor. The results suggests that gastric cancer patients with high CD8-positive T-cell infiltration may be more responsive to anti-programmed death 1/-programmed death ligand-1 mAb therapy. This article is protected by copyright. All rights reserved.

Screening endoscopy for gastric cancer: time for quality control.

Function-preserving surgery for gastric cancer: current status and future perspectives.

The number of early gastric cancer (EGC) cases has been increasing because of improved diagnostic procedures including endoscopy and screening systems. Therefore, function-preserving gastrectomy (FPG) for EGC with the expectation of better quality of life (QOL) after surgery may be increasingly utilized, due to its association with low rate of lymph node metastasis and excellent survival and the possibility of employing less invasive procedures such as laparoscopic gastrectomy in combination. Pylorus-preserving gastrectomy (PPG) with curative intent lymph node dissection is a representative FPG that has been used in EGC, and its superiorities, indications, limitations, and survival benefits have already been reported in several retrospective studies. Laparoscopic proximal gastrectomy (LAPG) has also been employed in EGC of the upper third of the stomach; however, LAPG was found to be associated with major issues in achieving a balance between swallowing and reflux prevention. In patients with EGC in the upper third of the stomach, laparoscopy-assisted subtotal gastrectomy with a preserved, albeit very small, stomach may provide a better QOL and fewer postoperative complications. FPG is recommended as a surgical treatment for EGC if the indication is accurately diagnosed and strictly confirmed; however, these techniques in laparoscopic surgery present technical difficulties to surgeons without a certain degree of skills. Although many retrospective studies revealed the functional benefits or oncological safety with FPG, further prospective studies using large case series are necessary to reveal the value of FPG compared with the conventional procedures.

Age and Outcome in Gastrointestinal Cancers: A Population-Based Evaluation of Oesophageal, Gastric and Colorectal Cancer.

With demographic changes and partial representativeness of randomized studies the question arises which results are achieved in the treatment of the elderly. The objective was to analyse population-based data on gastrointestinal cancers in terms of age.

Association between four SNPs in IL-4 and the risk of gastric cancer in a Chinese population.

Gastric cancer (GC) is the 5th most prevalent cancer. The etiology of GC is still poorly understood. We performed a case-control study in a Chinese population to investigate the association of rs2243248 (-1098 G/T), rs2227284 (-33 C/T), rs2243250 (-589 T/C) and rs2070874 (-107 T/C) polymorphisms and haplotypes with the development of gastric cancer in a Chinese population. A total of 362 patients with gastric cancer and 384 controls were recruited between December 2013 and December 2015. Genotyping of rs2243248 (-1098 G/T), rs2227284 (-33 C/T), rs2243250 (-589 T/C) and rs2070874 (-107 T/C) was performed in a 384-well plate format on the sequenom MassARRAY platform, and analyzed by MALDI-TOF MS. The TC and CC genotypes of rs2243250 (-589 T/C) were associated with an increased risk of gastric cancer when compared with the TT genotype, with adjusted ORs (95% CI) of 1.52 (1.07-2.15) and 2.13 (1.30-3.51), respectively. The TTTT haplotype revealed a reduced risk of gastric cancer (OR=0.65, 95% CI=0.45-0.94). No linkage disequilibrium was found among IL-4 rs2243248, rs2227284, rs2243250 and rs2070874. In summary, our findings support a significant association of IL-4 rs2243250 polymorphism with the risk of gastric cancer in the Chinese population, and IL-4 haplotype contributes to the development of this disease.

Carbohydrate Antigen 19-9-Positive Gastric Adenocarcinoma: Autopsy Findings and Review of the Literature.

Carbohydrate antigen 19-9 (CA19-9) is a well-known tumor marker for pancreatobiliary cancer, and several studies have shown that an elevated serum CA19-9 level is associated with more aggressive biological behavior in gastric cancer (GC). However, the clinicopathological characteristics of CA19-9-positive GC remain unclear. We herein report an autopsy case of CA19-9-positive GC in an 84-year-old man who was admitted to our hospital because of paralysis and anemia. Autopsy revealed an ulcerative-invasive tumor measuring 72 × 60 mm in the anterior wall of the gastric body. The tumor had invaded beyond the muscularis propria, and metastasized to the lung, liver, and regional lymph nodes. Histologically, the tumor cell had oval nuclei with abundant clear cytoplasm, and tubular and/or papillary features with prominent lymphovascular permeation and perineural invasion, mimicking pancreatobiliary carcinoma. Immunohistochemically, the tumor cells showed diffuse immunopositivity for CA19-9 and carcinoembryonic antigen. According to a review of cases reported in the literature, CA19-9-positive GCs show clinicopathological characteristics such as antral location, ulcerative-infiltrating gross feature, differentiated histology, prominent lymphatic and venous invasion, higher proportion of metastasis, and higher clinical stage. These results suggest that CA19-9-positive GC is pathologically a distinctive type of tumor with aggressive biological behavior.

Malignant Gastric Outlet Obstruction from Pancreatic Cancer.

Patients with advanced-stage pancreatic cancer are typically burdened by many symptoms that impair functioning and worsen quality of life. We report an exceptional case of a 73-year-old woman with T4N1M0 adenocarcinoma of the uncinate process of the pancreas who developed significant gastric outlet obstruction - an uncommon yet potentially life-threatening complication of disease progression. She developed progressive abdominal pain and emesis, and profound dilatation of her stomach was detected on a radiation therapy simulation CT scan that required urgent decompression. Malignant gastric outlet obstruction must be included in the differential diagnosis when patients with known advanced disease of the pancreas present with obstructive upper gastrointestinal symptoms.

Clinicopathological features and prognoses in younger and older patients with gastric cancer.

Patients of different ages with gastric cancer (GC) have different clinicopathological features and prognoses. The results for different crowds are limited and controversial. The aim of this study was to investigate the differences in clinicopathological features and prognoses between younger and older GC patients.

In vivo evaluation of cetuximab-conjugated poly(γ-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts.

Epidermal growth factor receptor (EGFR), upregulated in gastric cancer patients, is an oncogene of interest in the development of targeted cancer nanomedicines. This study demonstrates in silico modeling of monoclonal antibody cetuximab (CET MAb)-conjugated docetaxel (DOCT)-loaded poly(γ-glutamic acid) (γ-PGA) nanoparticles (Nps) and evaluates the in vitro/in vivo effects on EGFR-overexpressing gastric cancer cells (MKN-28). Nontargeted DOCT-γ-PGA Nps (NT Nps: 110±40 nm) and targeted CET MAb-DOCT-γ-PGA Nps (T Nps: 200±20 nm) were prepared using ionic gelation followed by 1-Ethyl-3-(3-dimethyl aminopropyl)carbodiimide-N-Hydoxysuccinimide (EDC-NSH) chemistry. Increased uptake correlated with enhanced cytotoxicity induced by targeted Nps to EGFR +ve MKN-28 compared with nontargeted Nps as evident from MTT and flow cytometric assays. Nanoformulated DOCT showed a superior pharmacokinetic profile to that of free DOCT in Swiss albino mice, indicating the possibility of improved therapeutic effect in the disease model. Qualitative in vivo imaging showed early and enhanced tumor targeted accumulation of CET MAb-DOCT-γ-PGA Nps in EGFR +ve MKN-28-based gastric cancer xenograft, which exhibited efficient arrest of tumor growth compared with nontargeted Nps and free DOCT. Thus, actively targeted CET MAb-DOCT-γ-PGA Nps could be developed as a substitute to conventional nonspecific chemotherapy, and hence could become a feasible strategy for cancer therapy for EGFR-overexpressing gastric tumors.

Fracture of a Colonic Self-expandable Metallic Stent in Malignant Colonic Obstruction: A Case Report.

Self-expandable metallic stents (SEMSs) are used for the management of malignant colorectal obstruction. A patient who underwent colonic uncovered SEMS insertion for extraluminal stenosis in the splenic flexure of the transverse colon due to advanced gastric cancer is herein reported. The patient presented with a fracture of the colonic SEMS 494 days after SEMS insertion. Although various complications of stenting have previously been reported, the details of fractures of colonic SEMSs have not yet been reported. Because the improvement in the prognosis for patients who undergo palliative SEMS insertion leads to long-term SEMS placement, diverse complications can thus be expected, and new events like stent fracture are expected to increase in the future.

Current Techniques of Teaching and Learning in Bariatric Surgical Procedures: A Systematic Review.

The gastric sleeve resection and gastric bypass are the 2 most commonly performed bariatric procedures. This article provides an overview of current teaching and learning methods of those techniques in resident and fellow training.

Nodal areas of potential geographic error in adjuvant radiotherapy for biliary tract cancer.

To determine the areas of potential geographic error in adjuvant radiotherapy (RT) for biliary-tract cancer (BTC) by comparing pathological-surgical data on the pattern of nodal spread with the extent of elective nodal CTV used in published RT studies in this setting.

The expression level of miR-203 in patients with gastric cancer and its clinical significance.

The clinical significance of miR-203 and its prognostic value have not been investigated in gastric cancer.

Is it necessary to dissect the posterior lymph nodes along the splenic vessels during total gastrectomy with D2 lymphadenectomy for advanced gastric cancer?

D2 lymphadenectomy including No.10 lymph nodes (LNs) is the standard procedure for treating advanced gastric cancer (AGC) via total gastrectomy. However, there was no research focusing on the posterior LN dissection along the splenic vessels (No.10p LNs). This study is performed to assess the effect of dissecting No.10p LNs.

Basics in Endoscopic Ultrasound Part 1: Diagnostic Indications and Tissue Sampling.

Endoscopic ultrasound has been used in the clinical arena for almost 35 years and it is now well-integrated in everyday hospital practice.

Pyruvate Kinase Isozymes M2 and Glutaminase Might Be Promising Molecular Targets for the Treatment of Gastric Cancer.

The aim of this study was to analyze the significance of glucose metabolism-related enzymes in the proliferation of gastric cancer under hypoxia. Four hypoxia-resistant gastric cancer cell lines and 4 parent cell lines were used. RT-PCR was used to evaluate the mRNA expression levels of the following metabolism-related enzymes: pyruvate kinase isozymes M2 (PKM2), glutaminase (GLS), enolase 1 (ENO1), glucose-6-phosphate dehydrogenase (G6PDH), and PKM1. The effects of these enzymes on the proliferation of gastric cancer cells were examined using siRNAs, Shikonin as a PKM2 inhibitor, or BPTES as a GLS inhibitor, in vitro and in vivo. Levels of both PKM2 and GLS mRNA were significantly high in all hypoxia-resistant cell lines, compared with those of their parent cells. Knockdown of PKM2 and GLS significantly decreased the proliferation of all of hypoxia-resistant cells. The combination of siPKM2 and siGLS significantly decreased proliferation compared with treatment by siPKM2 or siGLS alone. The knockdown of ENO1, G6PDH, or PKM1 did not decrease the proliferation of all hypoxia-resistant cells. Combination treatment by Shikonin and BPTES inhibited the proliferation of all hypoxia-resistant cancer cells more than that by either one of the two agents. The in vivo study indicated that the tumor size treated by the combination of Shikonin and BPTES was significantly smaller than that of vehicle-treated group. These findings suggested that PKM2 and GLS might play important roles in the proliferation of hypoxic gastric cancer cells. A combination of PKM2 and GLS inhibitors might be therapeutically promising for the treatment of gastric cancer. This article is protected by copyright. All rights reserved.

Comparing intestinal versus diffuse gastric cancer using a PEFF-oriented proteomic pipeline.

Gastric cancer is the fifth most common malignant neoplasia and the third leading cause of cancer death worldwide. Mac-Cormick et al. recently showed the importance of considering the anatomical region of the tumor in proteomic gastric cancer studies; more differences were found between distinct anatomical regions than when comparing healthy versus diseased tissue. Thus, failing to consider the anatomical region could lead to differential proteins that are not disease specific. With this as motivation, we compared the proteomic profiles of intestinal and diffuse adenocarcinoma from the same anatomical region, the corpus. To achieve this, we used isobaric labeling (iTRAQ) of peptides, a 10-step HILIC fractionation, and reversed-phase nano-chromatography coupled online with a Q-Exactive Plus mass spectrometer. We updated PatternLab to take advantage of the new Comet-PEFF search engine that enables identifying post-translational modifications and mutations included in neXtProt's PSI Extended FASTA Format (PEFF) metadata. Our pipeline then uses a text-mining tool that automatically extracts PubMed IDs from the proteomic result metadata and drills down keywords from manuscripts related with the biological processes at hand. Our results disclose important proteins such as apolipoprotein B-100, S100 and 14-3-3 proteins, among many others, highlighting the different pathways enriched by each cancer type.

Long-term outcomes after noncurative endoscopic resection of early gastric cancer: the optimal time for additional endoscopic treatment.

We aimed to evaluate long-term outcomes with noncurative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and surveillance strategies such as the optimal time for additional endoscopic treatment in patients with noncurative ESD.

Complement C5a/C5aR pathway potentiates the pathogenesis of gastric cancer by down-regulating p21 expression.

Although the complement C5a/C5aR pathway is suggested to play a critical role in tumor pathogenesis, the underlying mechanism has yet to be fully elucidated. In the present study, we found that in patients with gastric cancer in different clinical stages (from stageⅠto stage Ⅳ), both C5aR and p-PI3K/AKT levels were significantly higher in tumoral tissues than in adjacent non-tumoral tissues. In contrast, p21/p-p21 levels were significantly lower in tumoral tissues than in adjacent non-tumoral tissues. In vitro recombinant C5a administration remarkably promoted p-PI3K/p-AKT expression, but inhibited p21/p-p21 expression. Blockage of C5a/C5aR signaling with a C5aR antagonist reversed the C5a-induced inhibitory effect on p21/p-p21 expression. C5a administration to cells pre-treated with a PI3K inhibitor also prevented this inhibitory effect, suggesting the involvement of the PI3K/AKT signaling pathway in C5a/C5aR-mediated suppression of p21/p-p21 expression. In vivo C5aR antagonist treatment caused significant reduction in tumor growth in mice, accompanied by a remarkable elevation in p21/p-p21 expression and reduction in p-PI3K/AKT activation. These results indicate that the C5a/C5aR pathway promotes gastric cancer pathogenesis by suppressing p21/p-p21 expression via activation of PI3K/AKT signaling.

Quality of life among Korean gastrointestinal cancer survivors.

The number of gastrointestinal (GI) cancer survivors has been steadily increasing owing to early diagnosis and improved cancer treatment outcomes. The quality of life (QoL) of cancer survivors can provide distinct prognostic information and represent their functioning. This study aimed to investigate the levels of symptoms, psychological distress, and QoL of GI cancer survivors, and identify factors associated with QoL.

PTEN Gene Induces Cell Invasion and Migration via Regulating AKT/GSK-3β/β-Catenin Signaling Pathway in Human Gastric Cancer.

Abnormality of PTEN gene and Wnt/β-catenin signaling have been strongly implicated in various malignant cancers. Recently, it has been noted that a functional interaction/cross-talk was found between the PTEN/PI3K/AKT and Wnt/β-catenin, which plays a key role in the development of cancers. However, few related studies on gastric cancer are available.

The optimal chemotherapeutic regimen in D2-resected locally advanced gastric cancer: a propensity score-matched analysis.

Adjuvant chemotherapy using TS-1 or capecitabine plus oxaliplatin improves survival outcomes after radical gastrectomy, with both regimens showing similar efficacies. A total of 494 patients with stage II‒III gastric cancer who underwent curative D2 gastrectomy and received adjuvant chemotherapy from April 2004 to June 2014 were included in this study. 219 patients received TS-1, and 275 received platinum-based chemotherapy. The disease-free survival associated with adjuvant chemotherapy with TS-1 was compared with that associated with fluoropyrimidine plus platinum chemotherapy to identify the subgroups that would benefit most from platinum-based chemotherapy. The platinum group consisted of younger individuals, more males and more stage III patients compared with the TS-1 group. To reduce selection bias and its effects on treatment results, we performed a propensity score-matched analysis. The matched cohort consisted of 219 TS-1 and 219 platinum treatment patients, respectively. In the matched cohort, the chemotherapeutic regimen did not affect disease-free survival according to stage (stage II: platinum vs. TS-1, P = 0.348; stage III: P = 0.132). According to the subgroup analysis, platinum-based chemotherapy resulted in an improved 3-year disease-free survival compared with TS-1 treatment (66.8% vs. 57.8%, P = 0.015) for patients with high-risk features (any two or more of pT4, pN3, and lymphovascular invasion positivity). Our results suggest that TS-1 alone is acceptable for patients without high-risk features, while platinum-based adjuvant chemotherapy should be administered to patients with high-risk features in D2-resected gastric cancer.

The roles of maspin expression in gastric cancer: a meta- and bioinformatics analysis.

Maspin is a mammary serine protease inhibitor that is encoded by human SERPINB5 gene, and inhibits invasion and metastasis of cancer cells as a tumor suppressor. We performed a systematic meta- and bioinformatics analysis through multiple online databases up to Feb 10, 2017. We found down-regulated maspin expression in gastric cancer, compared with normal mucosa and dysplasia (p < 0.05). Maspin expression was negatively correlated with depth of invasion, TNM staging and dedifferentiation of gastric cancer (p < 0.05). Nuclear maspin expression was higher in intestinal- than diffuse-type carcinoma (p < 0.05). An inverse association between maspin expression and unfavorable overall survival was found in patients with gastric cancer (p < 0.005). According to bioinformatics databases, SERPINB5 mRNA expression was higher in gastric cancer than normal tissues (p < 0.05), and negatively correlated with depth of invasion, TNM staging and dedifferentiation of gastric cancer (p < 0.05). According to KM plotter, we found that a higher SERPINB5 expression was positively correlated with overall and progression-free survival rates of all cancer patients, even stratified by aggressive parameters (p < 0.05). These findings indicated that maspin expression might be employed as a potential marker to indicate gastric carcinogenesis, subsequent progression, and even prognosis.

Development of mesenchymal subtype gene signature for clinical application in gastric cancer.

Previously, in the Asian Cancer Research Group (ACRG) project, we defined four distinct molecular subtypes in gastric cancer (GC). Mesenchymal (microsatellite stable with epithelial-to-mesenchymal transition phenotype, MSS/EMT) tumors showed the worst prognosis among all the subtypes. To develop a gene signature for predicting mesenchymal subtype GC, we conducted gene expression profiling using a NanoString assay in 70 ACRG specimens. The gene signature was validated in an independent set obtained from the prospective Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. The association between the mesenchymal subtype and survival was investigated. After cross-platform concordance test performed in 70 ACRG specimens, a 71-gene MSS/EMT signature was obtained. In the validation set, the gene signature predicted that 20 of 73 (27%) patients had mesenchymal tumors. Patients with mesenchymal subtype had diffuse GC, poorly-differentiated or signet ring cell carcinoma, and were microsatellite stable. The estimated hazard ratio for survival in patients with mesenchymal GC compared to those with non-mesenchymal tumors was 2.262 (95% confidence interval, 1.410 to 3.636; P=0.001). The survival difference remained significant when the subtypes were analyzed according to clinical prognostic parameters. This study suggested that the NanoString-based 71-gene signature for mesenchymal subtype is a strong predictor of the outcome in patients with GC.