Efficacy and Safety of Keverprazan Compared With Lansoprazole in the Treatment of Duodenal Ulcer: A Phase III, Randomized, Double-Blind, Multicenter Trial.

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.

Small intestinal angiosarcoma on clinical presentation, diagnosis, management and prognosis: A case report and review of the literature.

BACKGROUND: Angiosarcoma is a highly malignant soft-tissue sarcoma derived from vascular endothelial cells that mainly occurs in the skin and subcutaneous tissues. Small-intestinal angiosarcomas are rare, and the prognosis is poor. CASE SUMMARY: We reported a case of primary multifocal ileal angiosarcoma and analyze previously reported cases to improve our understanding of small intestinal angiosarcoma. Small intestinal angiosarcoma is more common in elderly and male patients. Gastrointestinal bleeding, anemia, abdominal pain, weakness, and weight loss were the common symptoms. CD31, CD34, factor VIII-related antigen, ETS-related gene, friend leukemia integration 1, and von Willebrand factor are valuable immunohistochemical markers for the diagnosis of small-intestinal angiosarcoma. Small-intestinal angiosarcoma most commonly occurs in the jejunum, followed by the ileum and duodenum. Radiation and toxicant exposure are risk factors for angiosarcoma. After a definite diagnosis, the mean and median survival time was 8 mo and 3 mo, respectively. Kaplan-Meier survival analysis showed that age, infiltration depth, chemotherapy, and the number of small intestinal segments invaded by tumor lesions were prognostic factors for small intestinal angiosarcoma. Multivariate Cox regression analysis showed that chemotherapy and surgery significantly improved patient prognosis. CONCLUSION: Angiosarcoma should be considered for unexplained melena and abdominal pain, especially in older men and patients with a history of radiation exposure. Prompt treatment, including surgery and adjuvant chemotherapy, is essential to prolonging patient survival.

Role of succinate dehydrogenase deficiency and oncometabolites in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. At the molecular level, GISTs can be categorized into two groups based on the causative oncogenic mutations. Approximately 85% of GISTs are caused by gain-of-function mutations in the tyrosine kinase receptor KIT or platelet-derived growth factor receptor alpha (PDGFRA). The remaining GISTs, referred to as wild-type (WT) GISTs, are often deficient in succinate dehydrogenase complex (SDH), a key metabolic enzyme complex in the tricarboxylic acid (TCA) cycle and electron transport chain. SDH deficiency leads to the accumulation of succinate, a metabolite produced by the TCA cycle. Succinate inhibits α-ketoglutarate-dependent dioxygenase family enzymes, which comprise approximately 60 members and regulate key aspects of tumorigenesis such as DNA and histone demethylation, hypoxia responses, and m6A mRNA modification. For this reason, succinate and metabolites with similar structures, such as D-2-hydroxyglutarate and fumarate, are considered oncometabolites. In this article, we review recent advances in the understanding of how metabolic enzyme mutations and oncometabolites drive human cancer with an emphasis on SDH mutations and succinate in WT GISTs.

Circular RNA is a popular molecule in tumors of the digestive system (Review).

Most tumors of the digestive system, including esophageal, gastric, liver and colorectal cancer, are malignant tumors that are associated with rates of high morbidity and mortality. The lack of effective methods for early diagnosis is an important cause of poor prognosis for these malignancies. Circular RNAs (circRNAs) belong to a family of endogenous, covalently closed non­coding RNAs that are characterized as having no 5' cap structures or 3' poly­A tails. Shortly following discovery, circRNAs were considered to be a product of mis­splicing and have no significant biological function. However, in recent years, accumulating evidence is demonstrating that they serve key roles in tumorigenesis and have the potential to serve as diagnostic markers. The present article summarizes the biogenesis and function of circRNAs and reviews their role in seven common types of tumor of the digestive system whilst exploring their potential as tumor markers and the significant roles they can serve in the digestive system, in addition to providing a referencing point for future studies of digestive system malignancies.

COL4A family: potential prognostic biomarkers and therapeutic targets for gastric cancer.

BACKGROUND: The type IV collagen alpha chain (COL4A) family is a major component of the basement membrane (BM) that has recently been found to be involved in tumor angiogenesis and progression. However, the expression levels and the exact roles of distinct COL4A family members in gastric cancer (GC) have not been completely understood. METHODS: Here, the expression levels of COL4As in GC and normal gastric tissues were calculated by using TCGA datasets and the predicted prognostic values by the GEPIA tool. Furthermore, the cBioPortal and Metascape tools were integrated to analyze the genetic alterations, correlations and potential functions of COL4As, and their frequently altered neighboring genes in GC. RESULTS: Notably, the expression levels of COL4A1/2/4 in GC were higher to those in normal gastric tissues, while the expression levels of COL4A3/5/6 were lower in GC than normal. Survival analysis revealed that lower expression levels of COL4A1/5 led to higher overall survival (OS) rate. Multivariate analysis using the Cox proportional-hazards model indicated that age, gender, pathological grade, metastasis and COL4A5 expression, are independent prognostic factors for OS. However, TNM stage, lymph node metastasis, Lauren's classification, COL4A1-4 and COL4A6 were associated with poor OS but not independent prognostic factors. Function-enriched analysis of COL4As and their frequently altered neighboring genes was involved in tumor proliferation and metastasis in GC. CONCLUSIONS: These results implied that COL4A1/2 were potential therapeutic targets for GC. COL4A3/4/6 might have an impact on gastric carcinogenesis and subsequent progression, whereas COL4A5 was an independent prognostic marker for GC.

Serum miR-551b-3p is a potential diagnostic biomarker for gastric cancer.

BACKGROUND/AIMS: Gastric cancer (GC) is one of the most common gastrointestinal malignancies. Many studies have demonstrated that serum microRNAs have potential applications as non-invasive biomarkers for cancer diagnosis. The aim of the present study was to investigate the expression of serum miR-551b-3p in patients with GC and to explore its potential as a diagnostic biomarker in GC. MATERIALS AND METHODS: The expression of miR-551b-3p was detected using quantitative reverse transcription polymerase chain reaction in preoperative serum samples of 50 patients with GC and 53 healthy individuals. An analysis was performed to determine the correlation between serum miR-551b-3p levels and clinicopathological characteristics of patients with GC. The receiver operating characteristic curve was generated, and the cut-off point of serum miR-551b-3p for the diagnosis of GC was selected. The clinical value of serum miR-551b-3p for GC was analyzed by a consistency test. RESULTS: The expression of serum miR-551b-3p was significantly lower in patients with GC than in healthy individuals (p=0.000). Low level was positively associated with tumor size (p=0.014), depth of invasion (p=0.001), and Tumor-Node-Metastasis stage (p=0.022). The area under the curve for serum miR-551b-3p distinguishing patients with GC from healthy individuals was 0.860 (95% CI: 0.787-0.933, p=0.000), with a specificity of 96.2% and a sensitivity of 70%. The kappa consistency test had a kappa value of 0.667 (p=0.000) in GC. CONCLUSION: Serum miR-551b-3p may potentially serve as a diagnostic biomarker for GC.

Celecoxib regulates apoptosis and autophagy via the PI3K/Akt signaling pathway in SGC-7901 gastric cancer cells.

Gastric cancer, one of the most common malignancies worldwide, typically has a poor prognosis and poor survival rate. Previous studies have investigated the chemopreventive effect of celecoxib. In the present study, the SGC-7901 human gastric cancer cell line was utilized to examine the chemopreventive mechanisms of celecoxib. The inhibition of cell proliferation was determined using MTT assay, cell apoptosis was monitored by terminal deoxynucleotidyl transferase-mediated dUTP nick end­labeling (TUNEL) and flow cytometry, and cell ultrastructural changes were assessed via transmission electron microscopy. The mRNA expression of Akt, caspase-8 and -9 was examined using quantitative reverse-transcription-polymerase chain reaction (qRT-PCR) and p-Akt, procaspase-8 and -9 were analyzed via western blotting. The results showed that celecoxib inhibited the proliferation of SGC-7901 cells in a time- and dose-dependent manner. Additionally, celecoxib induced apoptosis as substantiated by typical apoptotic bodies, autophagosomes and an increased apoptotic rate. It was found that following celecoxib treatment, Akt mRNA expression was not significantly altered, and that p-Akt protein levels decreased in a time- and dose­dependent manner. Additionally, caspase-8 and -9 mRNA expression was significantly increased, while procaspase-8 and -9 protein expression decreased relative to the time- and dose-dependent effects. These results demonstrated that celecoxib induced apoptosis and autophagy of gastric cancer cells in vitro through the PI3K/Akt signaling pathway. Moreover, our findings suggested that celecoxib induces apoptosis in gastric cancer cells through the mitochondrial and death receptor pathways, providing additional understanding regarding the chemopreventive behaviors of celecoxib and its uses in cancer therapy.

[Correlations of TGF-betaRII, Smad4 and Smad7 expression to clinicopathologic characteristics and prognosis of gastric cancer].

BACKGROUND AND OBJECTIVE: Recent studies have revealed that TGF-beta/Smads signaling pathway plays a pivotal role in the oncogenesis and development of malignant tumors, and may closely relate to the biological behaviors of some malignant tumors, such as gastric carcinoma. This study was to investigate the expression of transforming growth factor-beta receptor II (TGF-betaRII), Smad4 and Smad7 proteins in gastric carcinoma, and explore their correlations to clinicopathologic characteristics and prognosis of gastric carcinoma. METHODS: The expression of TGF-betaRII, Smad4, and Smad7 was detected by SABC immunohistochemistry and tissue microarray which containing 200 specimens of primary human gastric carcinoma and 56 specimens of adjacent gastric tissue. RESULTS: The positive rates of TGF-betaRII, Smad4, and Smad7 in gastric carcinomas were 25.5%, 67.0%, and 47.0%, respectively. TGF-betaRII expression was related with depth of invasion, lymph node metastasis, tumor differentiation, and Lauren classification (Chi2=6.214, Chi2=11.308, Chi2=14.633, and Chi2=8.216, respectively, all P<0.05). Smad4 expression was related with tumor differentiation and Lauren classification (Chi2=16.162 and Chi2=13.100, all P<0.05). Smad7 expression was related with tumor differentiation and Lauren classification (Chi2=4.710 and Chi2=5.297, all P<0.05). Smad4 expression was positively correlated to TGF-betaRIIexpression (r =0.191, P=0.007). Smad4 expression was related with patients' survival (Chi2=4.090, P=0.043). CONCLUSIONS: Abnormal expression of TGF-Smad signaling pathway proteins occurs in gastric carcinoma. Smad4-positive gastric carcinoma patients have better prognosis than Smad4-negative patients.

[Study on the vibrational spectra characterization of synthetic jadeite jade made by General electric Company].

The object of the present study is the synthetic jadeite jade produced by American General Electric Corporation. Fourier transform infrared spectroscopy (FTIR) and Laser Raman spectroscopy were used to test its spectral properties in order to examine the feature of this kind of synthetic jadeite jade by vibrational spectroscopy and to figure out the mark for discriminate synthetic jadeite jade from natural jadeite jade. The study shows that GE synthetic jadeite jade is identical with natural jadeite jade in the main on fingerprint region in FTIR; There are clearly differences in the 2 000 -4 000 cm(-1) functional region in FTIR: a group of frequencies at 3 375, 3 471 and 3 614 cm(-1) indicate vibration absorption of O-H. GE synthetic jadeite jade has proven consistent with natural jadeite jade in the laser Raman spectra by a group of sharp scattering peaks at 376, 700, 989 and 1 039 cm(-1). In addition these scattering peaks show an intact crystal shape. The FTIR peaks and Raman spectral peaks shift to higher frequencies showing GE synthetic jadeite jade lacking isomorphism of heavy positive ions.

Genetic polymorphisms in cytochrome P4502E1, alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males.

AIM: To evaluate the association between genetic polymorphisms in CYP2E1, ALDH2 and ADH1B and the risk of esophageal squamous cell carcinoma (ESCC) in a high risk area of Gansu Province, in Chinese males. METHODS: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP2E1*c1/*c2, ALDH2*1/*2 and ADH1B *1/*1 genotypes). A total of 80 esophageal cancer cases and 480 controls were recruited. RESULTS: Compared with controls, cases had a greater prevalence of heavier alcohol consumption (53.8% vs 16.2%) and a higher proportion of alcohol drinkers with >30 drink-years (28.8% vs 13.5%). Heavier alcohol consumption and alcohol drinking with >30 drink-years increased the risk of ESCC, with ORs (95% CI) of 3.20 (1.32-9.65) and 1.68 (0.96-3.21). CYP2E1 (*c1/*c1), ALDH2 (*1/*2) and ADH1B (*1/*1) genotype frequencies were higher among patients with squamous cell carcinomas, at a level close to statistical significance (P=0.014; P=0.094; P=0.0001 respectively). There were synergistic interactions among alcohol drinking and ALDH2, ADH1B and CYP2E1 genotypes. The risk of the ESCC in moderate-to-heavy drinkers with an inactive ALDH2 encoded by ALDH2*1/*2 as well as ADH1B encoded by ADH1B *1/*1 and CYP2E1 encoded by CYP2E1 *c1/*c1 was higher than that in the never/rare-to-light drinkers with an active ALDH2 (*1/*1 genotype) as well as ADH1B (*1/*2+*2/*2) and CYP2E1 (*c1/*c2+*c2/*c2) genotypes, with a statistically significant difference; ORs (95% CI) of 8.58 (3.28-22.68), 27.12 (8.52-70.19) and 7.64 (2.82-11.31) respectively. The risk of the ESCC in moderate-to-heavy drinkers with ALDH2 (*1/*2) combined the ADH1B (*1/*1) genotype or ALDH2 (*1/*2) combined the CYP2E1 (*c1/*c1) genotype leads to synergistic interactions, higher than drinkers with ALDH2 (*1/*1)+ADH1B (*1/*2+*2/*2), ALDH2 (*1/*1)+CYP2E1 (*c1/*c2+*c2/*c2) respectively , ORs (95% CI) of 7.46 (3.28-18.32) and 6.82 (1.44-9.76) respectively. Individuals with the ADH1B combined the CYP2E1 genotype showed no synergistic interaction. CONCLUSION: In our study, we found that alcohol consumption and polymorphisms in the CYP2E1, ADH1B and ALDH2 genes are important risk factors for ESCC, and that there was a synergistic interaction among polymorphisms in the CYP2E1, ALDH2 and ADH1B genes and heavy alcohol drinking, in Chinese males living in Gansu Province, China.