- Refractory gastric antral ulcers without Helicobacter pylori infection and non-steroidal anti-inflammatory drugs. [Journal Article]
- CJClin J Gastroenterol 2018 Feb 16
- Herein, we describe a rare case of refractory gastric antral ulcers. A woman in her 50 s was admitted to Nagoya City University Hospital with epigastric pain after being diagnosed with gastric antral...
Herein, we describe a rare case of refractory gastric antral ulcers. A woman in her 50 s was admitted to Nagoya City University Hospital with epigastric pain after being diagnosed with gastric antral submucosal tumor at another hospital. Findings from esophagogastroduodenoscopy and endoscopic ultrasound examination revealed that the lesion was a gastric ulcer. The patient had no Helicobacter pylori infection and no recent history of using non-steroidal anti-inflammatory drugs. On the basis of these findings, we diagnosed this as a case of refractory gastric antral ulcer (RGAU). RGAU is considered a new disease concept and detailed analyses are expected in the future.
- Methylation of the HOXA10 promoter directs miR-196b-5p dependent cell proliferation and invasion of gastric cancer cells. [Journal Article]
- MCMol Cancer Res 2018 Feb 16
- The cross-talk between epigenetics and miRNA expression plays an important role in human tumorigenesis. Herein, we investigated the regulation and role of miR-196b-5p in gastric cancer. Using quantit...
The cross-talk between epigenetics and miRNA expression plays an important role in human tumorigenesis. Herein, we investigated the regulation and role of miR-196b-5p in gastric cancer. Using quantitative real-time RT-PCR, we demonstrate that miR-196b-5p is significantly overexpressed in human gastric cancer tissues (P<0.01). In addition, we also found that HOXA10, the host gene for miR-196b-5p, is overexpressed and positively correlated with miR-196b-5p expression levels (P<0.001). Quantitative pyrosequencing methylation analysis of HOXA10 promoter, demonstrated significantly lower levels of promoter DNA methylation of HOXA10 in gastric cancer samples, as compared to normal gastric mucosa samples (non-tumor control). Using 5-Aza-2'-deoxycytidine, we confirmed that demethylation of HOXA10 promoter induces the expression of HOXA10 and miR-196b-5p in gastric cancer cell models. Using the Tff1-KO mouse model of gastric neoplasia, we detected hypo- methylation and overexpression of HOXA10 and miR-196b-5p in gastric tumors, as compared to normal gastric mucosa from Tff1-WT mice. Mechanistically, we also found that reconstitution of TFF1 in human gastric cancer cell models leads to an increase in HOXA10 promoter methylation with reduced expression of HOXA10 and miR-196b-5p. Functionally, we found that miR-196b-5p reconstitution promoted human gastric cancer cell proliferation and invasion in in vitro cell models. In summary, we demonstrate overexpression of miR-196b-5p in gastric cancer. Our results suggest that TFF1 plays an important role in suppressing the expression of miR-196b-5p by mediating DNA methylation of HOXA10 promoter. Loss of TFF1 expression may promote proliferation and invasion of gastric cancer cells through induction of promoter hypo-methylation and expression of the HOXA10-miR-196b-5p axis. Implications These results indicate that the loss of TFF1 could promote the aberrant HOXA10 and miR-196b-5p overexpression by demethylating HOXA10 promoter, which provide a new perspective of TFF1-HOXA10-miR-196b-5p functions in human gastric cancer.
- Expression of cell cycle regulators and frequency of TP53 mutations in high risk gastrointestinal stromal tumors prior to adjuvant imatinib treatment. [Journal Article]
- PlosPLoS One 2018; 13(2):e0193048
- Despite of multitude investigations no reliable prognostic immunohistochemical biomarkers in GIST have been established so far with added value to predict the recurrence risk of high risk GIST beside...
Despite of multitude investigations no reliable prognostic immunohistochemical biomarkers in GIST have been established so far with added value to predict the recurrence risk of high risk GIST besides mitotic count, primary location and size. In this study, we analyzed the prognostic relevance of eight cell cycle and apoptosis modulators and of TP53 mutations for prognosis in GIST with high risk of recurrence prior to adjuvant treatment with imatinib. In total, 400 patients with high risk for GIST recurrence were randomly assigned for adjuvant imatinib either for one or for three years following laparotomy. 320 primary tumor samples with available tumor tissue were immunohistochemically analyzed prior to treatment for the expression of cell cycle regulators and apoptosis modulators cyclin D1, p21, p16, CDK4, E2F1, MDM2, p53 and p-RB1. TP53 mutational analysis was possible in 245 cases. A high expression of CDK4 was observed in 32.8% of all cases and was associated with a favorable recurrence free survival (RFS), whereas high expression of MDM2 (12.2%) or p53 (35.3%) was associated with a shorter RFS. These results were independent from the primary KIT or PDGFRA mutation. In GISTs with higher mitotic counts was a significantly increased expression of cyclin D1, p53 and E2F1. The expression of p16 and E2F1 significantly correlated to a non-gastric localization. Furthermore, we observed a significant higher expression of p21 and E2F1 in KIT mutant GISTs compared to PDGFRA mutant and wt GISTs. The overall frequency of TP53 mutations was low (n = 8; 3.5%) and could not be predicted by the immunohistochemical expression of p53. In summary, mutation analysis in TP53 plays a minor role in the subgroup of high-risk GIST before adjuvant treatment with imatinib. Strong expression of MDM2 and p53 correlated with a shorter recurrence free survival, whereas a strong expression of CDK4 correlated to a better recurrence free survival.
- Phase 1b study of pasireotide, everolimus, and selective internal radioembolization therapy for unresectable neuroendocrine tumors with hepatic metastases. [Journal Article]
- CCancer 2018 Feb 16
- CONCLUSIONS: The recommended phase 2 dose of everolimus is 10 mg daily in combination with pasireotide and SIRT. The regimen is well tolerated. Preliminary activity appears promising. Cancer 2018. © 2018 American Cancer Society.
- Outermost layer-oriented medial approach for infrapyloric nodal dissection in laparoscopic distal gastrectomy. [Journal Article]
- SESurg Endosc 2018 Feb 15
- CONCLUSIONS: This novel outermost layer-oriented medial approach is a robust procedure that may help laparoscopic surgeons in performing safe and reproducible infrapyloric nodal dissection.
- CD44v6 increases gastric cancer malignant phenotype by modulating adipose stromal cell-mediated ECM remodeling. [Journal Article]
- IBIntegr Biol (Camb) 2018 Feb 16
- CD44, an abundantly expressed adhesion molecule, and its alternative splice variants have been associated with tumorigenesis and metastasis. In the context of gastric cancer (GC), de novo expression ...
CD44, an abundantly expressed adhesion molecule, and its alternative splice variants have been associated with tumorigenesis and metastasis. In the context of gastric cancer (GC), de novo expression of CD44 variant 6 (CD44v6) is found in more than 60% of GCs, but its role in the pathogenesis and progression of this type of cancer remains unclear. Using a combination of media conditioning experiments and decellularized extracellular matrices (ECMs), this study investigates the hypothesis that CD44v6 overexpression enhances tumor cell malignant behavior by modulating stromal cell-mediated ECM remodeling. Our findings indicate that soluble factors secreted by CD44v6 expressing GC cells particularly increase proliferation and myofibroblastic differentiation of adipose stromal cells (ASCs). These changes in ASC phenotype mediate the deposition of fibrotic/desmoplastic ECM that, in turn, stimulates GC proliferation and inhibits GC clustering. Pharmacological inhibition of matrix metalloproteinase (MMP) activity in tumor cells abrogated matrix-induced changes in tumor cell malignant behavior. Additionally, studies in mice confirmed the pathological relevance of CD44v6 expression and consequential changes in ECM remodeling to gastric tumorigenesis in vivo. Collectively, these results indicate a direct link between CD44v6, ECM remodeling, and GC malignant behavior opening new insights into potential CD44v6-targeted therapies.
- Gastric metastasis from cervix carcer: a case report. [Journal Article]
- PPathologica 2017; 109(4):398-400
- Gastric metastasis by solid tumor cancer is a rare event. Concomitant metastases to other organs are frequent, so that this condition is often associated to a poor prognosis. Upper gastrointestinal b...
Gastric metastasis by solid tumor cancer is a rare event. Concomitant metastases to other organs are frequent, so that this condition is often associated to a poor prognosis. Upper gastrointestinal bleeding and anemia are the most common presenting symptoms. We present the case of a 81 years old women previously treated for cervix carcinoma showing later a stomach metastasis. The patient is alive and disease free 39 months after salvage gastrectomy. A radical surgery in selected patients could be useful for symptom palliation and prolonged survival.
- G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain-independent manner. [Journal Article]
- CDCell Death Dis 2018 Feb 15; 9(3):278
- Tumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis,...
Tumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis, and the mechanisms underlying tumor metastasis remain unclear. In the present study, increased histone methyltransferase G9A expression in GC tissues correlated with advanced stage and shorter overall survival, and in vitro and in vivo experiments revealed that G9A promoted tumor invasion and metastasis. Moreover, we observed that Reg IV induced G9A via the p-ERK/p-SP1 pathway. SP1 directly binds the G9A promoter and enhances G9A expression, and upregulated G9A then forms a transcriptional activator complex with P300 and GR, thereby promoting ITGB3 expression induced by dexamethasone (DEX) and contributing to GC metastasis. However, the G9A-mediated increase in ITGB3 expression was not dependent on the SET domain and methyltransferase activity of G9A. This study demonstrates that G9A is an independent prognostic marker and promotes metastasis in GC, thus suggesting that it may be a tumor biomarker and potential therapeutic target in GC.
- Overexpression of Lymphocyte Antigen 6 Complex, Locus E in Gastric Cancer Promotes Cancer Cell Growth and Metastasis. [Journal Article]
- CPCell Physiol Biochem 2018 Feb 09; 45(3):1219-1229
- CONCLUSIONS: LY6E over-expression in GC is potentially required for cancer cell survival, proliferation and migration.
New Search Next
- Over-expression of BCAT1 is a prognostic marker in gastric cancer. [Journal Article]
- HPHum Pathol 2018 Feb 12
- As one form of branched chain amino-acid transaminase(BCAT) enzymes, It has been found that up-regulation of BCAT1 is associated with poor prognosis in numerous types of tumors, but studies on the ro...
As one form of branched chain amino-acid transaminase(BCAT) enzymes, It has been found that up-regulation of BCAT1 is associated with poor prognosis in numerous types of tumors, but studies on the role of BCAT1 expression in gastric cancer(GC) are rare. The aim of this study was to detect BCAT1 expression in (GC) and to analyze its association with prognosis of GC patients. Microarray experiments were performed on the Affymetrix U133 plus 2.0 GeneChip Array. The protein and mRNA levels of BCAT1 were validated by immunohistochemistry (IHC) and Real-Time quantitative PCR (RT-qPCR) in GC tissues and adjacent noncancerous tissues (ANCT). Our study shows that the expression of BCAT1 significantly increased in human gastric cancer. Furthermore, it can also be found that BCAT1 over-expression was associated with TMN stage (P < .05), local invasion (P < .05), Lauren type (P < .05), tumor classification(P < .05), lymph node metastasis (P < .05) and presence of distant metastasis (P < .05).Kaplan-Meier survival analysis revealed that high BCAT1 expression predicted significantly worse over survival(OS) (P < .05) while Multivariate Cox regression analysis showed that BCAT1 affects gastric cancer independently. In conclusion, up-regulation of BCAT1 indicated a poor survival rate of gastric cancer and may serve as a useful marker for predicting the outcome of patients with GC.