PurposeWe previously demonstrated that the functional inactivation of DAL-1 and TOB1 promotes an aggressive phenotype in gastric cancer cells, but the links between both genes and the survival of patients with gastric cancer are unknown. Here, we investigated the correlations of the expression levels of DAL-1 and TOB1 with the progression of gastric cancer.MethodsA total of 270 patients who underwent resectable gastrectomy were included. The expression of DAL-1 and TOB1 was detected by immunohistochemistry.ResultsLow expression of DAL-1 in cancer tissue was significantly associated with tumor site (p < 0.05), histological grade (p < 0.01), depth of invasion (p < 0.05), lymph node metastasis status (p < 0.05), Lauren classification (p < 0.001), and clinical stage (p < 0.01). A lower level of TOB1 was observed in gastric cancer patients with diffuse type disease compared to patients with either intestinal or mixed type disease (p < 0.001). Additionally, Spearman’s correlation analysis revealed that decreased expression of DAL-1 was positively correlated with low TOB1 expression (r=0.304, p < 0.001). The survival analysis showed that low levels of DAL-1 and TOB1 were significantly associated with poor survival of gastric cancer patients (p <0.001 and p < 0.05, respectively).ConclusionThe downregulation of DAL-1 and TOB1 expression is associated with shorter survival of gastric cancer patients. Hence, DAL-1 and TOB1 may be considered potential novel markers for predicting the outcomes of patients with gastric cancer. 相似文献
1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.
2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.
3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A2/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos. 相似文献
Programmed death ligand 1(PD-L1) mediated immune escape play important roles in the development of cancer. The gene polymorphism of PD-L1, in particular rs4143815 C?>?G, has been associated with the cancer risks, but with conflicting results. Therefore, this meta-analysis was aimed to assess the association between rs4143815 C?>?G and cancer susceptibility. A systematic literature search was performed to select the studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Eleven eligible studies containing 3711 cases and 3704 controls were enrolled in the meta-analysis. The results suggested that there is a strong association between rs4143815 C?>?G and the cancer risks (G vs. C: OR?=?1.386, 95% CI: 1.132–1.696, p?=?0.002; GG vs. CG?+?CC: OR?=?1.843 95% CI: 1.300–2.613, p?=?0.002; GG?+?CG vs. CC: OR?=?1.280, 95% CI: 1.040–1.576, p?=?0.020). Subgroup analysis based on cancer type suggested that PD-L1 rs4143815 C?>?G might increase the susceptibility to gastric cancer (G vs. C: OR?=?1.842, 95% CI: 1.403–2.418, p?<?0.001) and bladder cancer (G vs. C: OR?=?2.015, 95% CI: 1.556–2.608, p?<?0.001), and genotype GG carriers of PD-L1 rs4143815 C?>?G might have higher risks of HCC (GG vs. CG?+?CC: OR?=?2.226 95% CI: 1.562–3.172, p?<?0.001). PD-L1 rs4143815 C?>?G might confer an increased cancer risk, indicating this SNP may contribute to the pathogenesis of cancer and might be used as a potential biomarker to predict the susceptibility to cancer. 相似文献
IntroductionEndoscopic surveillance guidelines for patients with repaired esophageal atresia (EA) rely primarily on expert opinion. Prior to embarking on a prospective EA surveillance registry, we sought to understand EA surveillance practices within the Eastern Pediatric Surgery Network (EPSN).MethodsAn anonymous, 23-question Qualtrics survey was emailed to 181 physicians (surgeons and gastroenterologists) at 19 member institutions. Likert scale questions gauged agreement with international EA surveillance guideline-derived statements. Multiple-choice questions assessed individual and institutional practices.ResultsThe response rate was 77%. Most respondents (80%) strongly agree or agree that EA surveillance endoscopy should follow a set schedule, while only 36% claimed to perform routine upper GI endoscopy regardless of symptoms. Many institutions (77%) have an aerodigestive clinic, even if some lack a multi-disciplinary EA team. Most physicians (72%) expressed strong interest in helping develop evidence-based guidelines.ConclusionsOur survey reveals physician agreement with current guidelines but weak adherence. Surveillance methods vary greatly, underscoring the lack of evidence-based data to guide EA care. Aerodigestive clinics may help implement surveillance schedules. Respondents support evidence-based protocols, which bodes well for care standardization. Results will inform the first multi-institutional EA databases in the United States (US), which will be essential for evidence-based care.Level of EvidenceThis is a prognosis study with level 4 evidence. 相似文献
Diabetes mellitus is a chronic metabolic disorder that has a complex molecular and cellular pathophysiology, resulting in its dynamic progression and that may show differing responses to therapy. The incidence of diabetes mellitus increases with age and requires additive therapeutic agents for its management. SGLT2i and DPP-4 inhibitors and GLP-1 receptor agonists (GLP-1RA) are newly introduced antidiabetic drugs that work through differing mechanisms; DPP-4 inhibitors maintain the endogenous level of GLP1; GLP-1RA result in pharmacological levels of GLP1, whilst SGLT2i act on the proximal tubules of the kidney. They have shown efficacy in the management of diabetes and in contrast to other antidiabetic drugs, do not inherently cause hypoglycemia in therapeutic doses. Autophagy as a highly conserved mechanism to maintain cell survival and homeostasis by degradation of damaged or aged organelles and components, and recognised to be increasingly important in diabetes. In the present review, we discuss the modulatory effects of these newly introduced antidiabetic drugs on the autophagy process. 相似文献
PurposeTo examine what proportion of caregivers, if given a choice, would choose medical versus surgical treatment of appendicitis and what factors would be important in their decision.MethodsA survey was devised and given to the caregivers of children presenting to the pediatrician for a routine visit in community and academic pediatric clinics. The survey presented a summary of outcomes after medical (non-operative) and surgical treatment of uncomplicated appendicitis. Participants were then asked to choose medical versus surgical treatment if their child were to develop appendicitis. They were also asked to rate the importance of certain factors in their decision ? 1 being “not important” and 5 being “very important”.ResultsFour hundred surveys were distributed with an 86.2% (345/400) response rate. Six percent (21/342) of respondents reported a history of appendicitis and 49.4% (168/340) reported having known someone who had appendicitis. The majority of respondents, 85.3% (284/333), were mothers. A minority of respondents, 41.7% (95% CI: 36.7, 47.0), chose medical treatment over surgery for appendicitis. There was no statistical difference in the proportion of mothers (41.6%) versus fathers who chose medical treatment (41.3%). Caregivers who chose medical treatment were more likely to rate time in hospital (p = .008) and time out of school (p = 05) as important in decision making when compared with those who chose surgery. Those who chose surgical treatment were more likely to rate risk of recurrent appendicitis (p < .001) as important to decision making. In the multivariate analysis, those who rated time in hospital as very important had more than twice the odds of choosing medical therapy (OR 2.20, p = 0.02) when compared with those who rated it as less important. Not knowing someone who has had appendicitis was significantly associated with choosing medical therapy when compared with those who do know someone who has had appendicitis, OR 2.3, p = .002. Rating pain as very important was also significantly associated with choosing medical therapy, when compared to those rating pain 1–3, OR 3.38, p = .03.ConclusionsIn this survey of caregivers of children presenting for routine care, 41.7% would choose medical, or non-operative, therapy for their children with acute appendicitis. The risk of recurrence, time in hospital, and time out of school, pain, and knowing someone who has had appendicitis were all important factors that families may consider when making a decision. These data may be useful for surgeons counseling patients on which treatment to pursue. 相似文献