World Journal of Gastrointestinal Pathophysiology最新文献

In the world, hepatocellular carcinoma (HCC) is among the top 10 most prevalent malignancies. HCC formation has indeed been linked to numerous etiological factors, including alcohol usage, hepatitis viruses and liver cirrhosis. Among the most prevalent defects in a wide range of tumours, notably HCC, is the silencing of the p53 tumour suppressor gene. The control of the cell cycle and the preservation of gene function are both critically important functions of p53. In order to pinpoint the core mechanisms of HCC and find more efficient treatments, molecular research employing HCC tissues has been the main focus. Stimulated p53 triggers necessary reactions that achieve cell cycle arrest, genetic stability, DNA repair and the elimination of DNA-damaged cells' responses to biological stressors (like oncogenes or DNA damage). To the contrary hand, the oncogene protein of the murine double minute 2 (MDM2) is a significant biological inhibitor of p53. MDM2 causes p53 protein degradation, which in turn adversely controls p53 function. Despite carrying wt-p53, the majority of HCCs show abnormalities in the p53-expressed apoptotic pathway. High p53 in-vivo expression might have two clinical impacts on HCC: (1) Increased levels of exogenous p53 protein cause tumour cells to undergo apoptosis by preventing cell growth through a number of biological pathways; and (2) Exogenous p53 makes HCC susceptible to various anticancer drugs. This review describes the functions and primary mechanisms of p53 in pathological mechanism, chemoresistance and therapeutic mechanisms of HCC.

The expression of T-box transcription factor 3 (TBX3) has been identified in various cancers, including gastric cancers. Its role in breast cancers and melanomas has been intensively studied, and its contribution to the progression of cancers through suppressing senescence and promoting epithelial-mesenchymal transition has been reported. Recent reports on the role of TBX3 in gastric cancers have implied its involvement in gastric carcinogenesis. Considering its pivotal role in the initiation and progression of cancers, TBX3 could be a promising therapeutic target for gastric cancers.

Background: Cholangiocarcinoma (CCA) is an intractable cancer, and its incidence in northeastern Thailand is the highest worldwide. Infection with the liver fluke Opisthorchis viverrini (OV) has been associated with CCA risk. However, animal experiments have suggested that OV alone does not induce CCA, but its combination with a chemical carcinogen like nitrosamine can cause experimentally induced CCA in hamsters. Therefore, in humans, other environmental and genetic factors may also be involved.

Aim: To examine relations between risk for CCA and genetic polymorphisms in carcinogen-metabolizing and inflammation-related genes.

Methods: This hospital-based case-control study enrolled 95 case-control pairs matched by age (± 5 years) and sex. We examined relations between risk for CCA and genetic polymorphisms in carcinogen-metabolizing and inflammation-related genes, serum anti-OV, alcohol consumption, and smoking. Polymorphisms of CYP2E1, IL-6 (-174 and -634), IL-10 (-819), and NF-κB (-94) and their co-occurrence with polymorphisms in the drug-metabolizing enzyme gene GSTT1 or GSTM1 were also analyzed.

Results: Although CCA risk was not significantly associated with any single polymorphism, persons with the GSTT1 wild-type and CYP2E1 c1/c2 + c2/c2 genotype had an increased risk (OR = 3.33, 95%CI: 1.23-9.00) as compared with persons having the GSTT1 wild-type and CYP2E1 c1/c1 wild genotype. The presence of anti-OV in serum was associated with a 7- to 11-fold increased risk, and smoking level was related to an OR of 1.5-1.8 in multivariable analyses adjusted for each of the seven genetic polymorphisms.

Conclusion: In addition to infection with OV, gene-gene interactions may be considered as one of the risk factors for CCA development.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is now established as the salvage procedure of choice in patients who have uncontrolled or severe recurrent variceal bleeding despite optimal medical and endoscopic treatment.

Aim: To analysis compared the performance of eight risk scores to predict in-hospital mortality after salvage TIPS (sTIPS) placement in patients with uncontrolled variceal bleeding after failed medical treatment and endoscopic intervention.

Methods: Baseline risk scores for the Acute Physiology and Chronic Health Evaluation (APACHE) II, Bonn TIPS early mortality (BOTEM), Child-Pugh, Emory, FIPS, model for end-stage liver disease (MELD), MELD-Na, and a novel 5 category CABIN score incorporating Creatinine, Albumin, Bilirubin, INR and Na, were calculated before sTIPS. Concordance (C) statistics for predictive accuracy of in-hospital mortality of the eight scores were compared using area under the receiver operating characteristic curve (AUROC) analysis.

Results: Thirty-four patients (29 men, 5 women), median age 52 years (range 31-80) received sTIPS for uncontrolled (11) or refractory (23) bleeding between August 1991 and November 2020. Salvage TIPS controlled bleeding in 32 (94%) patients with recurrence in one. Ten (29%) patients died in hospital. All scoring systems had a significant association with in-hospital mortality (P < 0.05) on multivariate analysis. Based on in-hospital survival AUROC, the CABIN (0.967), APACHE II (0.948) and Emory (0.942) scores had the best capability predicting mortality compared to FIPS (0.892), BOTEM (0.877), MELD Na (0.865), Child-Pugh (0.802) and MELD (0.792).

Conclusion: The novel CABIN score had the best prediction capability with statistical superiority over seven other risk scores. Despite sTIPS, hospital mortality remains high and can be predicted by CABIN category B or C or CABIN scores > 10. Survival was 100% in CABIN A patients while mortality was 75% for CABIN B, 87.5% for CABIN C, and 83% for CABIN scores > 10.