R-Etodolac decreases β-catenin levels along with survival and proliferation of hepatoma cells

Behari, Jaideep; Zeng, Gang; Otruba, Wade; Thompson, Michael D.; Müller, Peggy; Micsenyi, Amanda; Sekhon, Sandeep; Leoni, Lorenzo M.; Monga, Satdarshan P.

doi:10.1016/j.jhep.2006.11.017

Cited by 72 publications

(50 citation statements)

References 38 publications

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“…Cieply et al [20] noticed that the overexpression of GS is highly correlated with b-catenin mutation and proposed GS as an overall reliable marker of b-catenin activation secondary to its mutation. Behari et al [21] proposed that targeting b-catenin might be an attractive approach to HCC treatment. Luca DT et al suggested that, in keeping with this early role in hepatic tumorigenesis, GS overexpression did not associate with tumor dedifferentiation [22], which is confirmed by the present findings.…”

Section: Discussionmentioning

confidence: 99%

Expression level of glutamine synthetase is increased in hepatocellular carcinoma and liver tissue with cirrhosis and chronic hepatitis B

et al. 2010

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Studies have suggested that glutamine synthetase (GS) is a potential marker of hepatocellular carcinoma (HCC). We aimed to evaluate the expression of GS in non-malignant liver tissue and serum GS levels in HCC, liver cirrhosis (LC), chronic hepatitis B (CHB), five kinds of extrahepatic diseases patients and healthy subjects. Immunohistochemistry (IHC) was used to assess GS expression in 260 liver tissue samples (from 120 HCC, 90 CHB stage 4, and 50 CHB stage 1-3 patients). Enzymelinked immunosorbent assays of 325 samples (from 100 healthy donors, 33 CHB stage 1-3, 43 CHB stage 4, 111 HCC, and 45 extrahepatic diseases patients) were used to further analyze GS levels in serum. IHC studies showed the expression of GS in 70% of HCC patients, 46.7% of CHB stage 4 patients and 38% of CHB stage 1-3 patients. The v 2 tests showed significant difference between HCC samples and non-tumor tissues (P = 0.001 for HCC vs. CHB stage 4, P = 0.000 for HCC vs. CHB). Consistent with this, serum GS levels are increased in HCC and CHB stage 1-4 patients. There are significant differences among all samples (P = 0.000 for all), except CHB stage 1-3 versus CHB stage 4 (P = 0.552). Based on multiple linear regressions, HCC, CHB stage 1-4 and AFP were significantly associated with serum GS levels. In addition, in HCC group, TNM and Child-Pugh were significantly associated with GS levels. Expression of GS is increased in HCC, LC, and CHB. It may be a new serum marker for liver disease.Keywords Glutamine synthetase Á Hepatocellular carcinoma Á Liver cirrhosis Á Chronic hepatitis B Á Regeneration Á Receiver operating characteristic curve Á Sensitivity and specificity Abbreviations

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Section: Discussionmentioning

confidence: 99%

Expression level of glutamine synthetase is increased in hepatocellular carcinoma and liver tissue with cirrhosis and chronic hepatitis B

et al. 2010

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“…In liver tumor cells, we have found that targeting ␤-catenin with an experimental drug, R-Etodolac, leads to decreased proliferation and survival of two human hepatoma cell lines (HepG2 and Hep3B). 56 This drug is an enantiomer of Etodolac, an NSAID used in inflammatory diseases of the joints. REtodolac lacks any cox-inhibitory activity or its notorious side effects and is already in phase II trials for refractory chronic lymphocytic leukemia.…”

Section: Wnt/␤-catenin In Hepatic Tumorsmentioning

confidence: 99%

WNT/β‐catenin signaling in liver health and disease

2007

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Wnt/␤-catenin signaling is emerging as a forerunner for its critical roles in many facets of human biology. Its roles in embryogenesis, organogenesis, and maintaining tissue and organ homeostasis demonstrate its munificent character. Its roles in pathological conditions such as cancer and other human disorders such as inflammatory disorders and fibrosis reveal its villainous disposition. In liver, it also maintains its dual personality and is clearly of essence in several physiological events such as development, regeneration, and growth. Its aberrant activation is also evident in many different tumors of the liver, and recent studies are beginning to identify its role in additional hepatic pathological conditions. It is contributing to liver physiology and pathology by regulating various basic cellular events, including differentiation, proliferation, survival, oxidative stress, morphogenesis, and others. This review discusses the contribution of the Wnt/␤-catenin signaling pathway in these events and simultaneously provides an essential overview of the major developments in the field of Wnt/␤-catenin and liver pathobiology. In addition, areas that are currently deficient or understudied are identified and discussed along with the avenues of translational and clinical relevance. (HEPATOLOGY 2007;45:1298-1305

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“…It has been shown that pharmacologic inhibition of -catenin decreases survival of hepatoma cells (Behari et al, 2007). Inactivation of -catenin suppressor APC led to spontaneous development of HCC in a mice model, suggesting the direct contribution from activated Wnt signaling to hepatocarcinogenesis (Colnot et al, 2004).…”

Section: Wwwintechopencommentioning

confidence: 99%