Advances of diagnostic and mechanistic studies of γ-glutamyl transpeptidase in hepatocellular carcinoma

Xia, Jufeng; Song, Peipei; Sun, Zhipeng; Sawakami, Tatsuo; Jia, Ming; Wang, Zhigang

doi:10.5582/ddt.2016.01052

Cited by 37 publications

(37 citation statements)

References 53 publications

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“…We also did not analyse the predictive value of steatosis, being overweight, tobacco, coffee, chocolate, or cannabis consumption, physical exercise, or long‐term drug use, all of which may be associated with fibrosis or the risk of PLC. However, GGT was highly associated with the risk of PLC, probably due to its association with cytotoxicity factors such as alcohol and metabolic factors . Indeed, the presence of type‐ 2‐diabetes was predictive of PLC (Table S7), although it was not associated with cirrhosis at inclusion, suggesting a mechanism independent of the progression of fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…However, GGT was highly associated with the risk of PLC, probably due to its association with cytotoxicity factors such as alcohol and metabolic factors. [16][17][18] Indeed, the presence of type-2-diabetes was predictive of PLC (Table S7), although it was not associated with cirrhosis at inclusion, suggesting a mechanism independent of the progression of fibrosis. The association between non-alcoholic fatty liver disease and the risk of hepatocellular cancer, was not validated in a systematic review 35 but it was strongly suspected in patients without cirrhosis.…”

Section: Limitationsmentioning

confidence: 99%

“…GGT was the third component of interest, as several studies have demonstrated its strong independent predictive value for PLC. Although the underlying mechanisms are unclear, GGT is significantly associated with cytotoxicity induced by cholestatic and metabolic disorders, as well as with excessive alcohol consumption …”

Section: Introductionmentioning

confidence: 99%

“…Although the underlying mechanisms are unclear, GGT is significantly associated with cytotoxicity induced by cholestatic and metabolic disorders, as well as with excessive alcohol consumption. [16][17][18] Alpha2-macroglobulin (A2M), is a multifunctional binding protein with protease and cytokine scavenging properties that has been studied as a marker of liver fibrosis. 4,19 So far, no direct association with PLC has been reported in either humans or rodent models.…”

Section: Introductionmentioning

confidence: 99%

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LCR1 and LCR2, two multi‐analyte blood tests to assess liver cancer risk in patients without or with cirrhosis

Poynard

Peta

Deckmyn

et al. 2018

Aliment Pharmacol Ther

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Summary Background No blood test has been shown to be effective in the prediction of primary liver cancer in patients without cirrhosis. Aim To construct and internally validate two sequential tests for early prediction of liver cancer. These tests enable an algorithm which could improve the performance of the standard surveillance protocol recommended (imaging with or without AFP), limited to patients with cirrhosis. Methods We performed a retrospective analysis in prospectively collected specimens from an ongoing cohort. We designed an early sensitive high‐risk test (LCR1) that combined (using Cox model) hepatoprotective proteins (apolipoproteinA1, haptoglobin) with known risk factors (gender, age, gammaglutamyltranspeptidase), and a marker of fibrosis (alpha2‐macroglobulin). To increase the specificity, we then combined (LCR2) these components with alpha‐fetoprotein. Results A total of 9892 patients, 85.9% without cirrhosis, were followed up for 5.9 years [IQR: 4.3‐9.4]. LCR1 and LCR2 time‐dependent AUROCs were not different in construction and validation randomised subsets. Among 2027 patients with high‐LCR1 then high‐LCR2, 167 cancers (113 with cirrhosis, 54 without cirrhosis) were detected, that is 12 patients needed to screen one cancer. The negative predictive value was 99.5% (95% CI 99.0‐99.7) in the 2026 not screened patients (11 cancers without cirrhosis) higher than the standard surveillance, which detected 113 cancers in 755 patients screened, that is seven patients needed to screen one cancer, but with a lower negative predictive value 98.0% (97.5‐98.5; Z = 4.3; P < 0.001) in 3298 not screened patients (42 cancers without cirrhosis). Conclusions In patients with chronic liver disease the LCR1 and LCR2 tests identify those with a high risk of liver cancer, including in those without cirrhosis. NCT01927133.

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Section: Discussionmentioning

confidence: 99%

Section: Limitationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

LCR1 and LCR2, two multi‐analyte blood tests to assess liver cancer risk in patients without or with cirrhosis

Poynard

Peta

Deckmyn

et al. 2018

Aliment Pharmacol Ther

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“…Hepatocellular carcinoma (HCC) remains a severe health threat worldwide [1][2][3] . Many patients are not diagnosed until advanced stages and require systemic chemotherapy [4][5][6] .…”

Section: Introductionmentioning

confidence: 99%

Capsaicin enhances the antitumor activity of sorafenib in hepatocellular carcinoma cells and mouse xenograft tumors through increased ERK signaling

Zhang

Zhao

et al. 2017

Acta Pharmacol Sin

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Sorafenib, a small inhibitor of tyrosine protein kinases, is currently the standard chemotherapy drug for the treatment of advanced hepatocellular carcinoma (HCC). Although sorafenib improves the survival of HCC patients, its efficacy is not optimal and requires further improvement. Capsaicin, the major active component of chili peppers from the genus Capsicum, is not only the agonist of TRPV1 channel, but also displays antitumor activity and enhances the sensitivity of cancer cells to cytotoxic drugs. In this study, we investigated the antitumor effects of combined sorafenib and capsaicin on HCC cells in vitro and xenograft tumors. Treatment with capsaicin alone dose-dependently inhibited the proliferation of the HCC cell lines PLC/PRF/7, HuH7 and HepG2 with IC values of 137, 108 and 140.7 μmol/L, respectively. No obvious expression of TRPV1 channel was detected in the 3 HCC cell lines and TRPV1 channel blockers did not alleviate the cytotoxicity of capsaicin. By contrast, combining capsaicin and sorafenib significantly enhanced the suppression on cell proliferation, achieving a high-level synergistic effect (inhibition rates over 50%) and promoting HCC cell apoptosis. In nude mice with PLC/PRF/5 xenografts, combined administration of capsaicin and sorafenib significantly enhanced the suppression on tumor growth without apparent gross toxicity compared to either agent alone. Mechanistically, capsaicin (10-200 μmol/L) dose-dependently increased the levels of phosphorylated ERK (p-ERK) in PLC/PRF/5 cells, thus leading to enhanced sorafenib sensitivity and a synergistic suppression on the tumor cells. Taken together, our results suggest that capsaicin-increased phosphorylation of ERK contributes to the enhanced antitumor activity of sorafenib, and capsaicin may be useful in improving the efficacy of sorafenib for the treatment of HCC.

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Liver Transplantation for Hepatocellular Carcinoma: Malatya Experience and Proposals for Expanded Criteria

Ince

Akbulut

Otan

et al. 2020

J Gastrointest Canc

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Advances of diagnostic and mechanistic studies of γ-glutamyl transpeptidase in hepatocellular carcinoma

Cited by 37 publications

References 53 publications

LCR1 and LCR2, two multi‐analyte blood tests to assess liver cancer risk in patients without or with cirrhosis

LCR1 and LCR2, two multi‐analyte blood tests to assess liver cancer risk in patients without or with cirrhosis

Capsaicin enhances the antitumor activity of sorafenib in hepatocellular carcinoma cells and mouse xenograft tumors through increased ERK signaling

Liver Transplantation for Hepatocellular Carcinoma: Malatya Experience and Proposals for Expanded Criteria

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