Hepatocellular Carcinoma From Epidemiology to Prevention: Translating Knowledge into Practice

Singal, Amit G.; El–Serag, Hashem B.

doi:10.1016/j.cgh.2015.08.014

Cited by 460 publications

(380 citation statements)

References 111 publications

(112 reference statements)

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“…Hepatocellular carcinoma (HCC) is one of the major causes of cancer-associated mortality worldwide, accounting for 5.7% of all newly diagnosed malignancies (1)(2)(3)(4)(5). The annual incidence rates of HCC are the highest in East Asia and Sub-Saharan Africa, where >80% of all known cases develop (1)(2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

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Prognostic significance of sarcopenia in patients with hepatocellular carcinoma undergoing sorafenib therapy

et al. 2017

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Abstract. The present study aimed to examine the impact of sarcopenia, defined as low muscle mass on computed tomography (CT), prior to sorafenib therapy on the clinical outcomes of patients with hepatocellular carcinoma (HCC) receiving sorafenib therapy. In total, 232 patients with unresectable HCC (median age, 72 years) were analyzed, and the extent of sarcopenia was assessed using CT. Cross-sectional areas (cm 2 ) of the skeletal muscles at the third lumbar vertebra level were determined by manual outlining on the CT images. The cross-sectional areas were normalized for height [skeletal rates, progression-free survival (PFS) rates and best treatment response of the sarcopenia group were retrospectively compared with those of the non-sarcopenia group, and the factors associated with OS and PFS were examined. Sarcopenia was observed in 151 patients (65.1%). There were 165 patients with Child-Pugh A and 67 with Child-Pugh B cirrhosis. In the sarcopenia group, the median treatment duration was 66 days, whereas in the non-sarcopenia group it was 103 days (P=0.001). The median OS time was 174 days in the sarcopenia group and 454 days in the non-sarcopenia group (P<0.0001). The median PFS was 77 days in the sarcopenia group and 106 days in the non-sarcopenia group (P=0.0131). Multivariate analysis identified sarcopenia to be an independent predictor of OS (hazard ratio, 0.365; P<0.0001). The objective response rate and disease control rate in the sarcopenia group were significantly lower, compared with those in the non-sarcopenia group (P=0.0146 and P=0.0151, respectively). In conclusion, sarcopenia may be an indicator of poor clinical course in patients with HCC receiving sorafenib. IntroductionHepatocellular carcinoma (HCC) is one of the major causes of cancer-associated mortality worldwide, accounting for 5.7% of all newly diagnosed malignancies (1-5). The annual incidence rates of HCC are the highest in East Asia and Sub-Saharan Africa, where >80% of all known cases develop (1-5). Advances in treatments for HCC during the last few decades markedly improved the prognosis of the disease (1,2,4,5). However, a curative therapy such as surgical resection may be applied to a limited number (<20%) of patients with HCC (5,6). Sorafenib is a multi-kinase inhibitor that suppresses cancer growth and cell proliferation (7,8). Two pivotal randomized phase III studies, namely the Sorafenib HCC Assessment Randomized Protocol study (7)

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Section: Introductionmentioning

confidence: 99%

“…The annual incidence rates of HCC are the highest in East Asia and Sub-Saharan Africa, where >80% of all known cases develop (1)(2)(3)(4)(5). Advances in treatments for HCC during the last few decades markedly improved the prognosis of the disease (1,2,4,5).…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of sarcopenia in patients with hepatocellular carcinoma undergoing sorafenib therapy

et al. 2017

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“…HCC commonly occurs in patients with chronic hepatitis or liver cirrhosis because of hepatitis B or C virus, alcohol, nonalcoholic steatohepatitis, or diabetes 2. The treatment of HCC follows well‐established guidelines 3, 4, 5.…”

Section: Introductionmentioning

confidence: 99%

Early experience of seven hepatocellular carcinoma cases treated with regorafenib

Uchikawa

Kawaoka

Kodama

et al. 2018

Clinical Case Reports

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“…Hepatocellular carcinoma (HCC) is one of the most common cancers and causes of cancer-related mortality worldwide [1][2][3] . Due to the lack of specific symptoms, the vast majority of HCCs are diagnosed at late and/ or advanced stages [4,5] .…”

Section: Introductionmentioning

confidence: 99%

Reversal of multidrug resistance of hepatocellular carcinoma cells by metformin through inhibitingNF-κBgene transcription

Yang

Wang

et al. 2016

WJH

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AIM:To interfere with the activation of nuclear factor-κB (NF-κB) with metformin and explore its effect in reversing multidrug resistance (MDR) of hepatocellular carcinoma (HCC) cells. METHODS:Expression of P-glycoprotein (P-gp) and NF-κB in human HepG2 or HepG2/adriamycin (ADM) cells RESULTS: P-gp overexpression in HepG2 and HepG2/ ADM cells was closely related to mdr1 mRNA (3.310 ± 0.154) and NF-κB mRNA (2.580 ± 0.040) expression. NF-κB gene transcription was inhibited by specific siRNA with significant down-regulation of P-gp and enhanced HCC cell chemosensitivity to doxorubicin. After pretreatment with metformin, HepG2/ADM cells were sensitized to doxorubicin and P-gp was decreased through the NF-κB signaling pathway. The synergistic effect of metformin and NF-κB siRNA were found in HepG2/ADM cells with regard to proliferation inhibition, cell cycle arrest and inducing cell apoptosis. Core tip: Metformin might target AMP-activated protein kinase mammalian target of rapamycin pathway, suppress hypoxia-inducible factor-1α and transcriptionally down-regulate P-glycoprotein (P-gp) and multidrug resistance (MDR)-associated protein 1, suggesting that metformin may reverse MDR by targeting the AMPactivated protein kinase/mammalian target of rapamycin/ hypoxia-inducible factor-1α/P-gp and MDR-associated protein 1 pathways. In the present study, HepG2/ADM cells pretreated with metformin were sensitized to doxorubicin and P-gp was decreased through the nuclear factor-κB (NF-κB) signaling pathway. The synergistic effects were found in the cells with regard to proliferation inhibition, cell cycle arrest and inducing apoptosis, and inhibiting P-gp expression via the NF-κB signaling pathway effectively reversed MDR by down-regulating MDR1/P-gp expression. CONCLUSION:

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Hepatocellular Carcinoma From Epidemiology to Prevention: Translating Knowledge into Practice

Cited by 460 publications

References 111 publications

Prognostic significance of sarcopenia in patients with hepatocellular carcinoma undergoing sorafenib therapy

Prognostic significance of sarcopenia in patients with hepatocellular carcinoma undergoing sorafenib therapy

Early experience of seven hepatocellular carcinoma cases treated with regorafenib

Reversal of multidrug resistance of hepatocellular carcinoma cells by metformin through inhibitingNF-κBgene transcription

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