Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemoprevention of hepatocellular carcinoma (HCC) is one of the most challenging aspects of medical research. Vitamin K2 (VK2) has been suggested for its chemopreventive role in treatment of HCC, while inconsistent results in clinical trials have been reported. The present study was initiated to add to our insight into the anti-HCC cell proliferative effect of VK2 and its derivatives from a viewpoint of chemical structure. No significant effect was observed with original VK2, while VK2 derivatives bearing both isoprene units and a carboxyl-terminated side chain dose-dependently inhibited the growth of HCC cells without affecting normal liver cells. Loss-of-function analyses revealed that the anti-HCC cell activity by the VK2 derivatives was not mediated by a VK2 binding protein Bcl-2 homologous antagonist/killer (Bak) but rather associated with caspase/transglutaminase-related signaling pathways. Further studies on the carboxylic derivatives of VK2 bearing isoprene structural units introduced in this study might shed new light on the systemic treatment and prevention of HCC.
...
PMID:Carboxylic Derivatives of Vitamin K2 Inhibit Hepatocellular Carcinoma Cell Growth through Caspase/Transglutaminase-Related Signaling Pathways. 2644 Jun 34

Transglutaminase 2 (TG2) is a ubiquitous multifunctional enzyme whose expression has been found to be altered in numerous studies of apoptosis and cell survival; its activity has been found to be increased in many types of cancer, where it is often over-expressed. Cisplatin has long been used as an effective therapeutic drug to treat numerous cancers. Although its activity is based on cross-linking of DNA, cisplatin may also operate via other mechanisms that involve modification and alteration in the activity of protein and RNA modulators of the cell cycle and apoptotic processes; these mechanisms are less well characterised. In this study, we investigated the effects of cisplatin-induced apoptosis on TG2 expression and activity in the human hepatocarcinoma (HepG2) cell line. Through a combination of Western blotting, enzymatic activity assays, flow cytometry and fluorescence microscopy we provide evidence that TG2 is inhibited during initiation of apoptosis by cisplatin, an observation that was reversed by increasing the expression of TG2, by treating cells with retinoic acid. We also report, for the first time, that cisplatin can directly inhibit transglutaminase activity in vitro. Collectively, these studies increase our understanding of the mechanism(s) of action of cisplatin, as cisplatin-mediated reduction in TG2 activity appears to act as an early activator of apoptosis during chemotherapeutic treatment of hepatocarcinoma cells. This observation suggests an explanation as to how increased levels of TG2 activity in cancer cells could contribute to chemotherapeutic resistance to cisplatin, and so has implications for novel approaches to cisplatin therapy.
 ...
PMID:Inhibition of Transglutaminase 2 activity increases cisplatin cytotoxicity in a model of human hepatocarcinoma chemotherapy. 2894 1

Background & aims Celiac disease (CD) is a multisystem disorder triggered by dietary gluten in genetically predisposed individuals that may affect any organ system, including the liver. We evaluated a change in patient model for end-stage liver disease (MELD)-Na and albumin level from the time of celiac disease diagnosis to six months later, after implementing a gluten-free diet. Methods A retrospective study was conducted from January 1, 2006, to June 30, 2018. CD was diagnosed based on celiac antibodies and/or histopathological data. MELD-Na and albumin were calculated at the start of the gluten-free diet and six months later. Additional variables like gender, ethnicity, serum IgA level, serum IgG level, human leukocyte antigen (HLA) type, and markers of end-stage liver disease were collected. Descriptive statistics, including means, were reported with the standard deviation for the continuous variables along with frequencies and percentages for all categorical variables. Results A total of 18 patients (55.6% male) were identified as having both cirrhosis and CD. The mean age at the time of celiac diagnosis was 53.6, and 94.4% were Caucasian. CD was diagnosed using celiac antibodies (100%) and histopathological data (44.4%). Most common celiac antibodies include anti-tissue transglutaminase antibodies (77.8%). End-stage liver disease markers like abdominal ascites (55.6%), variceal bleed (50.0%), acute or chronic kidney injury (16.7%), hepatocellular carcinoma (HCC) (11.1%), hepatic encephalopathy (HE) (50.0%), spontaneous bacterial peritonitis (SBP) (5.6%), and liver transplant (0.0%) were seen. The mean baseline MELD-Na score was 11.8, and albumin was 3.5 at the time of celiac diagnosis and mean MELD-Na was 11.8, and albumin was 3.5 six months after a gluten-free diet. Conclusion It is difficult to conclude any exact relationship between change in MELD-Na score after gluten-free diet, but an improving trend is noted in patients with higher MELD-Na score such as 17 or higher. There is no change or worsening of MELD-Na score in patients with lower MELD-Na score. There was no change in mean MELD-Na and albumin level after gluten-free diet.
 ...
PMID:Change in Patient MELD-Na and Albumin Level From the Time of Celiac Disease Diagnosis to Six Months Later After Gluten-Free Diet. 3258 96


<< Previous 1 2 3