Liver Cancer and Alcohol

Division of Liver Diseases, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1104, New York, NY 10029, USA. Electronic address: .
Clinics in liver disease (Impact Factor: 2.7). 11/2012; 16(4):839-50. DOI: 10.1016/j.cld.2012.08.011
Source: PubMed

ABSTRACT Annually, hepatocellular carcinoma is diagnosed in approximately a half-million people worldwide. Based on the association of alcohol with cancer, a International Agency for Research on Cancer working group recently deemed alcoholic beverages "carcinogenic to humans," causally related to occurrence of malignant tumors of the oral cavity, pharynx, larynx, esophagus, liver, colorectum, and female breast. Alcohol metabolism in the liver leads to reactive oxygen species production, induction of activity of cytochrome P450s, and reduction of antioxidants. This review analyzes the epidemiology and pathogenesis of alcohol in hepatocellular cancer.

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    • "and the occurrence of cancers in liver (Grewal P et al., 2012), breast (Brooks and Zakhari, 2013) and digestive tract (Haas et al., 2012) was also recognized. Additionally, obesity with physical inactivity was associated with a myriad of cancers such as breast cancer (Jain et al., 2013), thyroid cancer (Marcello et al., 2014), colorectal cancer (De Pergola and Silvestris, 2013) and gynecologic cancers (McTiernan et al., 2010; Schmandt et al., 2011). "
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    ABSTRACT: Multiple primary malignancies (MPM) have become increasingly prevalent worldwide. This investigation was aimed at establishing the clinicopathological characteristics of MPM patients and evaluating the impact of the living environment on MPM in the Taiwanese population. From January 2009 to December 2013, a total of 8,268 cancer patients were identified in our institutional center. Of these, 125 were diagnosed as MPM and thus enrolled. Data for clinicopathological features and treatment approaches for these MPM patients living in urban or suburb zone were obtained. Findings for the air pollution status in Taiwan were also collected. The most common cancer match of MPM was esophageal cancer with hypopharyngeal cancer (12.8%), followed by colorectal cancer with gastric cancer (6.4%) and colorectal cancer with breast cancer (5.6%). The air quality was significantly worse in the urban than in the suburban zone and there was a remarkably higher portion of MPM patients in the urban zone suffering from grade III and IV post-chemotherapeutic neutropenia (30.8% vs 15.1%, P=0.036). The tumor frequency and site distribution should be taken into the clinical evaluation because there is a relatively high risk of developing MPM. This study also highlighted the potential influence of environmental factors on post-chemotherapeutic neutropenia for patients with MPM.
    Asian Pacific journal of cancer prevention: APJCP 01/2015; 16(8):3533-8. · 2.51 Impact Factor
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    • "associated with chronic sleep problems and other pathologies ( Akerstedt, 2003; Anstey et al., 2009; Brower, 2001; Grewal and Viswanathen, 2012; Riley et al., 2011), it is important to understand the neurophysiological mechanisms through which EtOH affects circadian clock phase regulation. In this regard, we and others have shown that EtOH disrupts circadian rhythms through actions within and outside the SCN (Prosser and Glass, 2009; Rosenwasser et al., 2005; Spanagel et al., 2005). "
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    ABSTRACT: Ethanol (EtOH) triggers cellular adaptations that induce tolerance in many brain areas, including the suprachiasmatic nucleus (SCN), the site of the master circadian clock. EtOH inhibits light-induced phase shifts in the SCN in vivo and glutamate-induced phase shifts in vitro. The in vitro phase shifts develop acute tolerance to EtOH, occurring within minutes of initial exposure, while the in vivo phase shifts exhibit no evidence of chronic tolerance. An intermediate form, rapid tolerance, is not well studied but may predict subsequent chronic tolerance. Here, we investigated rapid tolerance in the SCN clock. Adult C57BL/6 mice were provided 15% EtOH or water for one 12-hour lights-off period. For in vitro experiments, SCN-containing brain slices were prepared in the morning and treated for 10 minutes with glutamate +/- EtOH the following night. Single-cell neuronal firing rates were recorded extracellularly during the subsequent day to determine SCN clock phase. For in vivo experiments, mice receiving EtOH 24 hours previously were exposed to a 30-minute light pulse immediately preceded by intraperitoneal saline or 2 g/kg EtOH injection. Mice were then placed in constant darkness and their phase-shifting responses measured. In vitro, the SCN clock from EtOH-exposed mice exhibited rapid tolerance, with a 10-fold increase in EtOH needed to inhibit glutamate-induced phase shifts. Co-application of brain-derived neurotrophic factor prevented EtOH inhibition, consistent with experiments using EtOH-naïve mice. Rapid tolerance lasts 48 to 96 hours, depending on whether assessing in vitro phase advances or phase delays. Similarly, in vivo, prior EtOH consumption prevented EtOH's acute blockade of photic phase delays. Finally, immunoblot experiments showed no changes in SCN glutamate receptor subunit (NR2B) expression or phosphorylation in response to rapid tolerance induction. The SCN circadian clock develops rapid tolerance to EtOH as assessed both in vivo and in vitro, and the tolerance lasts for several days. These data demonstrate the utility of the circadian system as a model for investigating cellular mechanisms through which EtOH acts in the brain.
    Alcoholism Clinical and Experimental Research 02/2014; 38(3). DOI:10.1111/acer.12303 · 3.31 Impact Factor
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    • "Most HCCs arise in a cirrhotic liver [5] and worldwide around 80% of them are related to a chronic infection with either hepatitis B (HBV) or hepatitis C virus (HCV) [6]. Moreover, a rising proportion of HCCs is ascribed to alcohol abuse and metabolic disorders [7] [8]. In the last years, the extensive heterogeneity of genomic lesions reported in HCCs has suggested that liver cancer is the result of a combination of both, genetic and epigenetic, alterations which affect more than one regulatory pathway [9] [10] [11] [12] [13] [14]. "
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    ABSTRACT: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. The lack of effective therapeutic options for advanced stage HCCs combined with an increasing incidence rate calls for the identification of early stage HCC molecular markers. SH2 Domain Containing 4A (SH2D4A) gene maps to human chromosome 8p21.3 and encodes for SH(2)A. The chromosomal region containing SH2D4A is frequently lost in colorectal, lung and HCC cancers. Our study aimed to investigate SH2D4A involvement in HCC pathogenesis combining mRNA expression, protein and clinical data. Transcriptome analysis performed on 37 HCC needle biopsies (matched with their corresponding non-neoplastic parenchyma) and five normal liver donor samples revealed that SH2D4A is downregulated in HCC. Results were confirmed by quantitative real-time-polymerase chain reaction (qRT-PCR), 25 out of 37 (67.6%) fresh frozen samples showed SH2D4A downregulation (p=0.026). Furthermore, combining qRT-PCR and immunohistochemistry data we demonstrated a direct correlation between SH2D4A mRNA and SH(2)A protein levels. The analysis of a tissue microarray (TMA) containing 336 specimens confirmed that SH(2)A is frequently reduced in HCC (56.8%) as well as in cirrhotic nodules (50.5%) compared to normal liver samples (31.1%). To conclude, our study revealed that SH2D4A is frequently downregulated in HCC samples thus corroborating its putative role as a tumour suppressor gene. In addition, we provide new evidence for SH2D4A involvement in HCC pathogenesis demonstrating for the first time its deregulation in cirrhotic nodules.
    European journal of cancer (Oxford, England: 1990) 12/2013; 50(4). DOI:10.1016/j.ejca.2013.11.018 · 4.82 Impact Factor
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