Hepatic cancer

The subject of chemically induced liver cancer is addressed in Chapter 32. 

The liver is essential in order to maintain life. Accordingly, xenobiotic attacks on it threaten life and well-being. Many chemicals are hepatotoxic, but mixtures of lipophilic and hydrophilic chemicals are liver toxins at exposure levels that are often far below those that are toxic for the single chemicals in those mixtures. Animal studies have demonstrated the 

Scorecard. Gastrointestinal or liver toxicants, www.scorecard.org/health-effects/chemicals-2. tcl short hazard name=liver all p=t 

Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes Carbon tetrachloride as a toxicological model. CritRev Toxicol 2003 33(2) 105 36. 

Lieber CS.. Alcoholic fatty liver Its pathogenesis and mechanism of progression to inflammation and fibrosis. Alcohol2004 34(1) 9 19. 

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This approach has been used primarily in Japan to treat patients with malignant, inoperable hepatic cancer. Mitomycin C contained in albumin microspheres was administered to patients (122) by percutaneous intraarterial catheterization. Tumor reduction was seen in over 68% of the cases. By contrast, the control group, receiving infusion therapy, had a poorer response. Survival times were also greater for patients receiving the microspheres. 

Preliminary observation on 16 cancer patients who have been treated with the above-mentioned total alkaloid preparation indicates that symptoms are improved. Thus hepatic cancer patients have claimed disappearance of pain, improvement of appetite, and reduction of ascites patients suffering esophageal cancer claimed to have the self-feeling of relaxation of pain and disappearance of vomiting and upset stomach as well as the improvement of appetite. These preliminary results are quite encouraging, but certainly more extensive investigations are needed before the antitumor action of the Gelsemium alkaloids can be established. 

Wilson s disease is an autosomal recessive disorder characterized by the accumulation of copper in liver and brain [21]. Hepatic involvement may result in liver cirrhosis and hepatic cancer. The deposition of copper in the basal ganglia results in a variety of movement disorders, including... 

The likelihood that this presentation is an adverse reaction in the liver increases linearly with an increasing score. The maximum score is 14, and scores below 7 are associated with an ever-decreasing likelihood that the drug or drug combination in question caused the problem. This approach is not designed for the assessment of hepatic cancers or cirrhotic conditions. 

Other applications of QCM biosensors include real-time monitoring of the agglutination process of human hepatic normal cells (L-02) and hepatic cancer cells (Bel7402) on QCM electrode in the absence and presence of ConA and wheat germ agglutinin.70 This work demonstrated that the QCM measurement technique based on cell agglutination can be used for discriminating hepatic normal cells from hepatic cancer cells. 

Cytokines such as interferons are used for the treatment of hepatitis, cancer, and lymphoma interleukins are used to enhance immune response and growth factors are used for the treatment of anemia and regulation of tumor angiogenesis. 

One major question is whether humans are at risk from these chemicals. Although they clearly have the receptor for the lipid-lowering drugs to work, there is no evidence of increased risk of hepatic cancer from epidemiological studies. However, fibrates are relatively weak PPARa agonists. 

Fujimoto, S., Miyazaki, M., et al. Biodegradable mitomycin C microspheres given intraarterially for inoperable hepatic cancer With particular reference to a comparison with continuous infusion of mitomycin C and 5-fluorouracil. Cancer. 56(10) 2404-2410. 

The exact mechanism(s) by which peroxisomal proliferating agents such as DEHP induce hepatic cancer in rodents are not precisely known, but might be related to the modulation of peroxisomal P oxidation, the... 

Studies have indicated that repeated exposure of dinitrotoluene has resulted in testicular atrophy and disturbances in the spermatogenesis cycle in experimental mice, rats, and dogs. Female mice also revealed nonfunctioning ovaries 89,90 Conflicting reports regarding the potential reproductive toxicity of dinitrotoluene among workers demand more confirmatory data 91,92 NIOSH has classified technical dinitrotoluene as a human reproductive health hazard in industrial workplaces. Isomers of dinitrotoluene have caused complete liver cancers in animals, but technical-grade dinitrotoluene failed to induce any kind of hepatic cancer in humans.37,93... 

Hepato toxicity Liver, bile duct, and gall bladder. The liver is particularly susceptible to xenobiotics due to its large blood supply and its role in metabolism Steatosis (lipid accumulation in hepatocytes) Chemical hepatitis (inflammation of the liver) Hepatic necrosis (death of the hepatocytes) Hepatic cancer (cancer of the liver) Hepatic cirrhosis (chronic fibrosis) Hypersensitivity (immune reaction resulting in hepatic necrosis)... 

Bisc e, A.M., Hoofnagle, J.H. Elevations in serum alpha-fetoprotein levels in patients with chronic B-hepatitis. Cancer 1989 64 2117-2120... 

Nakajo, M., Kobayashi, H., Shimabukuro, K., Shirono, K., Sakata, H Taguchi, M., Uchiyama, N., Sonoda, T., and Shinohara, S. (1988) Biodistribution of in vivo kinetics of Iodine-131 lipiodol infused via the hepatic artery of patients with hepatic cancer. J. Nucl. Med. 29,1066-1077. 

Zhang et al. have reported formulation of microemulsion of norcanthridin, an anticancer agent used for hepatic cancers [116]. The microemulsions were composed of lecithin, ethanol and ethyl oleate. The mean residence time, area under the curve (drug availability) and the liver concentrations of norcanthridin were significantly higher for the microemulsions as compared to that of the marketed formulation. 

Hepatic cancer Serum a-fetoprotein Different N-Unked glycoforms 2... 

Inhalation and oral bioassays using rats and mice have been conducted (NCI 1977 NTP 1986). These data provide sufficient evidence to conclude that tetrachloroethylene is carcinogenic in animals. However, the oral study (NCI 1977) was limited by control groups smaller than treatment groups, decreased survival, and dose adjustments during the study. A dermal study conducted in mice reported no incidence of cancer in the test animals (Van Duuren et al. 1979). No additional cancer bioassays in animals appear to be necessary at this time. However, additional studies that clarify the relationship between peroxisome proliferation and hepatic cancers in mice as well as the relevance of hepatic glutathione conjugation of tetrachloroethylene to hiunans would be useful. 

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