DE NOVO HEPATOCELLULAR CARCINOMA WITHOUT CHRONIC LIVER DISEASE BUT WITH 17 YEARS OF AZATHIOPRINE IMMUNOSUPPRESSION

1987 ◽  
Vol 43 (4) ◽  
pp. 597-599 ◽  
Author(s):  
&NA;
Gut ◽  
2019 ◽  
Vol 68 (9) ◽  
pp. 1676-1687 ◽  
Author(s):  
Mateus T Guerra ◽  
Rodrigo M Florentino ◽  
Andressa Franca ◽  
Antonio C Lima Filho ◽  
Marcone L dos Santos ◽  
...  

Background & objectivesHepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide. Several types of chronic liver disease predispose to HCC, and several different signalling pathways have been implicated in its pathogenesis, but no common molecular event has been identified. Ca2+ signalling regulates the proliferation of both normal hepatocytes and liver cancer cells, so we investigated the role of intracellular Ca2+ release channels in HCC.DesignExpression analyses of the type 3 isoform of the inositol 1, 4, 5-trisphosphate receptor (ITPR3) in human liver samples, liver cancer cells and mouse liver were combined with an evaluation of DNA methylation profiles of ITPR3 promoter in HCC and characterisation of the effects of ITPR3 expression on cellular proliferation and apoptosis. The effects of de novo ITPR3 expression on hepatocyte calcium signalling and liver growth were evaluated in mice.ResultsITPR3 was absent or expressed in low amounts in hepatocytes from normal liver, but was expressed in HCC specimens from three independent patient cohorts, regardless of the underlying cause of chronic liver disease, and its increased expression level was associated with poorer survival. The ITPR3 gene was heavily methylated in control liver specimens but was demethylated at multiple sites in specimens of patient with HCC. Administration of a demethylating agent in a mouse model resulted in ITPR3 expression in discrete areas of the liver, and Ca2+ signalling was enhanced in these regions. In addition, cell proliferation and liver regeneration were enhanced in the mouse model, and deletion of ITPR3 from human HCC cells enhanced apoptosis.ConclusionsThese results provide evidence that de novo expression of ITPR3 typically occurs in HCC and may play a role in its pathogenesis.


Diagnostics ◽  
2015 ◽  
Vol 5 (2) ◽  
pp. 189-199 ◽  
Author(s):  
Sandi Kwee ◽  
Linda Wong ◽  
Brenda Hernandez ◽  
Owen Chan ◽  
Miles Sato ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Hailemichael Desalegn Mekonnen ◽  
Henok Fisseha ◽  
Tewodros Getinet ◽  
Fisseha Tekle ◽  
Peter R. Galle

Background and Aims.Hepatocellular carcinoma is a major cause of cancer death worldwide, accounting for over half a million deaths per year. Its incidence varies with geographic locations and the type of etiologic factors. In Ethiopia, unidentified causes of liver disease are of sizeable proportion. Recent studies have shown an association of H. pylori infection with different spectrums of chronic liver disease. This study was conducted at St. Paul’s Hospital Millennium Medical College in Ethiopia and assesses liver cancer and the association with H. pylori infection.Method.A prospective case-control study conducted on patients with chronic liver disease presenting with a suspicious liver lesion and diagnosed to have HCC in the Gastrointestinal (GI) Clinic of St. Paul’s Hospital MMC from Dec 30, 2016, to Nov 1, 2017 G.C. Descriptive surveys on clinical history and physical examination and laboratory profiles were obtained, and the clinical course of the patients including the type of treatment was followed prospectively. Control cases were taken from adult patients without evidence of liver disease in the internal medicine clinic coming for routine evaluation. After collection data were analyzed using SPSS version 23 and associations were assessed using chi-square test. Binary logistic regression was used to assess the association of HCC with different variables and H. pylori infection. All variables with p-value <0.05 were considered as statistically significant.Results.One hundred twenty patients were analyzed with equal representation of cases and controls. The majority of patients with HCC were male with a mean age of 36 years. Older age adjusted Odds Ratio (AOR) (95%CI, p-value) 1.07(1.03-1.09, <0.001), viral hepatitis B (AOR) (95%CI, p-value) 6.19 (1.92-19.93, 0.002), and H. pylori infection (AOR) (95%CI, p-value) 5.22 (2.04–13.31, <0.001) were statistically significantly associated with HCC.Conclusion.H. pylori infection is associated with HCC in this case-control study. This study supports the emerging evidence of H. pylori association with other extra-gastric manifestations.


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