Studies investigating the association between p53 codon 72 polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline and Embase databases. This meta-analysis included 12 case-control studies, which included 1,665 gastric cancer cases and 2,358 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [Arg/Arg odds ratio (OR) 5 0.96, 95% confidence interval (CI) 5 0.79, 1.16; Pro/Pro (OR 5 1.21, 95% CI 5 0.92, 1.58); Pro/Arg (OR 5 0.95, 95% CI 5 0.79, 1.14)] between gastric cancer and noncancer patients. When stratifying for race, results were similar except that patients with gastric cancer had a significantly lower frequency of Arg/Arg (OR 5 0.84, 95% CI 5 0.72, 0.99) than noncancer patients among Asians. Stratified the various studies by the location, stage, Lauren's classification, and histological differentiation of gastric cancer, we found that (i) patients with cardia gastric cancer had a significantly higher frequency of Pro/Pro (OR 5 3.20, 95% CI 5 1.46,7.01) than those with noncardia gastric cancer among Asians; (ii) patients with advanced (stage III/IV) gastric cancer had a significantly higher frequency of Arg/ Arg (OR 5 1.48, 95% CI 5 1.01, 2.16) than those with early (stage I/II) gastric cancer among Asians; (iii) patients with poor differentiation had a significantly lower frequency of Pro/Pro (OR 5 0.13, 95% CI 5 0.03, 0.64) than those with well differentiation among Caucasians. This meta-analysis suggests that the p53 codon 72 polymorphism may be associated with gastric cancer among Asians, and that difference in genotype distribution may be associated with the location, stage, and histological differentiation of gastric cancer. ' 2007 Wiley-Liss, Inc.Key words: gastric cancer; p53 codon 72; gene polymorphism; meta-analysis Gastric cancer, the second leading cause of death from cancer throughout the world, is an important health problem. A 2005 analysis of the worldwide incidence of and mortality from cancer showed that 934,000 cases of gastric cancer occurred in 2002 and that 700,000 patients die annually of this disease. 1 Despite the overall decline in gastric cancer rates in most of the Western World, gastric cancer remains a serious fatal disease throughout much of the rest of the world. Thirty-eight percent of worldwide cases occur in China, where it remains the most common cancer in both sexes as it is elsewhere in Eastern Asia. 2 Conversely, the incidence rates of adenocarcinomas of the proximal stomach and distal esophagus have been increasing, particularly in the Western World. 3 Gastric carcinogenesis is a complex, multistep and multifactorial process, in which many factors are implicated. The majority of gastric cancers are thought to be caused by environmental factors that result in damage to the mucosa and that inhibit its ability to repair itself. This response...
Objectives:Although targeted therapy has revolutionized the treatment of gastrointestinal stromal tumours (GIST), it is almost never curative in GIST, and resistance commonly develops. One potential strategy is to combine targeted therapy with immunotherapy. Materials and methods:We first studied Programmed cell death 1 ligand 1 (PD-L1) expression and tumour-infiltrating T cells (TILs) in GIST. IFN-γ was used to induce the upregulation of PD-L1 expression in GIST-882 cells, a well-known GIST cell line.CD8+ T-cell apoptosis was determined by flow cytometry. The PI3K/Akt/mTOR levels in CD8+ T cells were examined by Western blotting.Results: PD-L1 expression was an independent factor of poor prognosis in GIST and resulted in exhausted T cells in the TILs population or the blood. Then, we found that PD-L1 blockade alone could not increase tumour cell apoptosis in GIST. The apoptosis rate of CD8+ T cells was higher when T cells were cultured with PD-L1+ GIST-882 cells (GIST-882 cells with high PD-L1 expression) than when T cells were cultured with control GIST-882 cells. However, when the PD-L1 blockade was used, the apoptosis rates of the CD8+ T cells in the two groups became similar. Then, Western blotting showed the PI3K/Akt/mTOR levels of the CD8+ T cells rescued by the PD-1/ PD-L1 blockade were higher than those of the CD8+ T cells not treated with the PD-1/PD-L1 blockade.Conclusions: PD-L1 expression was an independent poor prognosis factor in GIST.PD-1/PD-L1 blockade rescued exhausted CD8+ T cells in GIST via the PI3K/Akt/ mTOR signalling pathway. In GIST, PD-1/PD-L1 not only function as predictive biomarkers but also improve current therapies as treatment targets.
Scope The aim of this article is to conduct an umbrella review to study the strength and validity of associations between tea consumption and diverse health outcomes. Methods and results Meta‐analyses of observational studies examining associations between tea consumption and health outcomes in all human populations and settings are screened. The umbrella review identifies 96 meta‐analyses with 40 unique health outcomes. Tea consumption shows greater benefits than harm to health in this review. Dose–response analyses of tea consumption indicates reduced risks of total mortality, cardiac death, coronary artery disease, stroke, and type 2 diabetes mellitus with increment of two to three cups per day. Beneficial associations are also found for several cancers, skeletal, cognitive, and maternal outcomes. Harmful associations are found for esophageal and gastric cancer when the temperature of intake is more than 55–60 °C. Conclusion Tea consumption, except for very hot tea, seems generally safe at usual levels of intake, with summary estimates indicating the largest reduction for diverse health outcomes at two to three cups per day. Generally, tea consumption seems more beneficial than harmful in this umbrella review. Randomized controlled trials are further needed to understand whether the observed associations are causal.
The present study was undertaken to clarify the association of the clinicopathological features of hepatoid adenocarcinoma (HAC) in the stomach, a special kind of carcinoma that histologically resembled hepatocellular carcinoma (HCC) and is characterized by large amounts of α-fetoprotein (AFP) in serum, with the clinical prognosis. We collected the data of the clinicopathological features and the follow-up information from a total of 31 HACs from January 2005 to December 2012 in our hospital. High lymphatic (54.8%) and distant (25.8%) metastasis rates before surgery, large proportion of advanced HACs (71.0%) at admission, short median overall survival time (6 months), and low three-year survival rate (22.6%) suggested that HAC in the stomach was an aggressive disease, resulting in a poor prognosis. And pTNM stages, immunohistochemical staining of AFP, CEA, CK7, and CK20 had statistically relation with the survival as the independent risk factors, P < 0.05. Therefore, early and clear differentiation of HAC from cancerous or noncancerous conditions with AFP elevation and assessment of high risk patients by histopathology may improve the clinical prognosis.
Rice is highly sensitive to cold stress during reproductive developmental stages, and little is known about the mechanisms of cold responses in rice anther. Using the HiSeq™ 2000 sequencing platform, the anther transcriptome of photo thermo sensitive genic male sterile lines (PTGMS) rice Y58S and P64S (Pei’ai64S) were analyzed at the fertility sensitive stage under cold stress. Approximately 243 million clean reads were obtained from four libraries and aligned against the oryza indica genome and 1497 and 5652 differentially expressed genes (DEGs) were identified in P64S and Y58S, respectively. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for these DEGs. Functional classification of DEGs was also carried out. The DEGs common to both genotypes were mainly involved in signal transduction, metabolism, transport, and transcriptional regulation. Most of the DEGs were unique for each comparison group. We observed that there were more differentially expressed MYB (Myeloblastosis) and zinc finger family transcription factors and signal transduction components such as calmodulin/calcium dependent protein kinases in the Y58S comparison group. It was also found that ribosome-related DEGs may play key roles in cold stress signal transduction. These results presented here would be particularly useful for further studies on investigating the molecular mechanisms of rice responses to cold stress.
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