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: 3.66).
11/2012; 16(4):839-50. DOI: 10.1016/j.cld.2012.08.011
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.
Available from: Chih-Chun Chang
- "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.
Available from: Mario Amicarelli
- "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.
Available from: Alejandra Ward
- "Additionally, in our previous work, we demonstrated that wild type MEFs that were chronically exposed to ethanol (EtOH) treatment, displayed a hypermethylated Plk4 promoter region resulting in a phenotype that resembles that seen in Plk4+/− cells with multi-nucleation and multiple-centrosome formation . Inherent to ethanol metabolism is the production of high levels of ROS  therefore, suggesting that ROS may also impact Plk promoter methylation. In order to examine whether Plk1 and Plk4 epigenetic marks were susceptible to modification as a result of high levels of ROS, we subjected Plk4+/+ and Plk4+/− MEFs to reactive oxygen species (ROS) by exposing them to hydrogen peroxide (H2O2) at a 200 um dose for a period of 18 hours. "
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ABSTRACT: The polo-like kinase (PLKs) family, consisting of five known members, are key regulators of important cell cycle processes, which include mitotic entry, centrosome duplication, spindle assembly, and cytokinesis. The PLKs have been implicated in a variety of cancers, such as hepatocellular carcinoma (HCC), with PLK1 typically overexpressed and PLKs 2-5 often downregulated. Altered expression of the PLKs in malignancy is often correlated with aberrant promoter methylation. Epigenetic marks are dynamic and can be modified in response to external environmental stimuli. The aim of our study was to determine if oxidative stress, a common feature of solid tumours, would induce changes to the promoter methylation of the PLKs resulting in changes in expression. We examined the promoter methylation status via MSP and subsequent expression levels of the PLK family members under exposure to hypoxic conditions or reactive oxygen species (ROS). Interestingly, murine embryonic fibroblasts exposed to hypoxia and ROS displayed significant hypermethylation of Plk1 and Plk4 promoter regions post treatment. Corresponding proteins were also depleted by 40% after treatment. We also examined the HCC-derived cell lines HepG2 and Hep3B and found that for PLK1 and PLK4, the increase in hypermethylation was correlated with the presence of functional p53. In p53 wild-type cells, HepG2, both PLK1 and PLK4 were repressed with treatment, while in the p53 null cell line, Hep3B, PLK4 protein was elevated in the presence of hypoxia and ROS. This was also the case for ROS-treated, p53 null, osteosarcoma cells, Saos-2, where the PLK4 promoter became hypomethylated and protein levels were elevated. Our data supports a model in which the PLKs are susceptible to epigenetic changes induced by microenvironmental cues and these modifications may be p53-dependent. This has important implications in HCC and other cancers, where epigenetic alterations of the PLKs could contribute to tumourigenesis and disease progression.
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