Primary hepatocellular carcinoma

Cell lines established from human liver cancer cells can be derived from primary hepatocellular carcinoma or hepatoblastoma cells [10]. For example, the well known HepG2 fine was derived from hepatoblastoma cells. Such cells can be employed effectively if the function of normal liver cells has been highly preserved. In practice, however, such cells contain a high proportion of abnormal genetic component, which inhibits their ability to express normal protein synthesis and enzyme activity. Potential problems, such as the loss of liver specific functions and the possibifity of metastasis, which could arise from the use of hepatoma cells have not yet been satisfactorily discussed [13]. 

Tumor-promoting effect. A 28-year-old man who abused alcohol, nicotine, and cannabis for several years was investigated. He suffered simultaneously from a squamous cell carcinoma of the hypopharynx with bilateral cervical metastases, an adenocarcinoma of the transverse colon and a primary hepatocellular carcinoma. There were occurrences of three separate malignant tumors with different histologies in the aerodigestive tract, which could be related to a chronic abuse of cannabis . 

Wogan, G. N. "Aflatoxins as risk factors for primary hepatocellular carcinoma in humans" In Mycotoxins, Cancer and Health Bray, G. A. and Ryan, D. H., Eds. Pennington Center Nutrition Series Louisiana State University Press Baton Rouge, LA, 1991, VoL 7, pp. 3-17. 

Robinson WS. The role of hepatitis B virus in the development of primary hepatocellular carcinoma Part I. J Gastroenterol Hepatol 1992 7 622-38. 

C. P. Wild et al, Molecular dosimetry of aflatoxin exposure contribution to understanding multifactorial etiopathogenesis of primary hepatocellular carcinoma with particular reference to hepatitis B virus . Environmental Health Perspectives, 99 (1993), 115-22. 

In countries with high prevalence of hepatitis B the virus is transmitted vertically (from mother to baby). Passive immunoprophylaxis with immime globulin given to the baby at birth, followed by vaccination, is effective at preventing chronic carriage. Mass vaccination should lead to a reduction in the incidence of primary hepatocellular carcinoma, but caimot yet be implemented in third world countries for want of funding. 

R Fulminant hepatic failure as the initial manifestation of primary hepatocellular carcinoma. Eur. X. Gastroenterol. Hepatol. 2000 12 ... 

Alward, W.L.M., McMahon, B.J., Hall, D.B., Heyward, W.L., Frauds, D.P., Bender, T.R. The long-term serological course of asymptomatic hepatitis B virus carriers and the development of primary hepatocellular carcinoma. J. Infect. Dis. 1985 151 604 -609... 

Blumberg, R.S., Chopra, S., Ibrahim, R., Crawford, X, Farraye, F.A., Zeldis, XB., Berman, M.D. Primary hepatocellular carcinoma in idiopathic hemochromatosis after reversal of cirrhosis. Gastroenterology 1988 95 1399-1402... 

Saurln, J.C., Tanlere, R, Mlon, F., Jacob, R, Partensky, C., Paliard, R, Berger, F. Primary hepatocellular carcinoma in workers exposed to vinyl chloride. A report of two cases. Cancer 1997 79 1671 -1677... 

Shepherd, F.A., Rotstein, L.E., Houle, S., Yip, T.C.K., Pani, K., Suider-man, K.W. A phase 1 dose escalation trial of yttrium microspheres in the treatment of primary hepatocellular carcinoma. Cancer 1992 ... 

O Reilly K, Snape J, Moore MR. Porphyria cutanea tarda resulting from primary hepatocellular carcinoma. Clin Exp Dermatol 1988 13 44-8. 

Feitelson M, Zhu M, Duan L, London W. Hepatitis B X antigen and p53 are associated in vitro and in liver tissues from patients with primary hepatocellular carcinoma. Oncogene 1993 8 1109-17. 

S, et al. Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med 1984 310 1427-31. 

Ohmi and Arias have investigated the plasma levels of alpha-class GST in hepatocellular carcinoma in the rat and humans (03). They found that serum ligandin concentrations rose progressively following the transplantation of a lig-andin-containing rat hepatocellular carcinoma in rats or athymic mice. The mean serum ligandin concentrations within 4 months exceeded normal serum levels by a factor of 10. When serum ligandin concentrations were studied in humans it was reported that levels were Increased in 11 of 15 patients with primary hepatocellular carcinoma. Normal levels were found in 19 of 22 patients with primary carcinomas without hepatic involvement. 

Summary Primary hepatocellular carcinoma is one of the most common cancers in the world and is prevalent on the continents of Africa and Asia. A number of classical epidemiological studies have determined that the exposure status of people to aflatoxin B1 is an important risk factor in the etiology of liver cancer. However, these studies have only relied upon the criteria of presumptive intake data, rather than information obtained from quantitative analyses of food samples, biological fluids and from people exposed to aflatoxin. Information obtained by monitoring exposed individuals for specific DNA adducts and metabolites will define the pharmacokinetics of aflatoxin B1 in people, thereby facilitating risk assessments. Preliminary data, reported here, support the concept that measurement of the major, rapidly excised AFB-N7-Gua adduct in urine and quantification of the more persistent aflatoxin albumin adduct are appropriate dosimeters for estimating exposure status and possibly risk in individuals consuming this mycotoxin. 

Hepatitis B is a common STD. During the past 10 years, sexual transmission accormted for approximately 30% - 60% of the estimated 240,000 new HBV infections that occurred ammally in the United States. Chronic HBV infection develops in 1% - 6% of persons infected as adults. These persons are capable of transmitting HBV to others, and they are at risk for chronic hver disease. In the United States, HBV infection leads to an estimated 6,000 deaths annually these deaths result from cirrhosis of the liver and primary hepatocellular carcinoma. 

Uroporphyrinogen decarboxylase (EC 4.1.1.37). The enzyme is unstable. Increased fecal excretion of uroporphyrin, porphyrins possessing 7 carboxylic add groups, copropoiphyrin and isocoproporphyrin. Phot ennatosis. Hepatic siderosis. Risk of primary hepatocellular carcinoma greatly increased. Treatment by phlebotomy. Autosomal dominant. The condition may also be induced by exposure to halogena-ted aromatic hydrocarbons (e.g. polychlorinated biphenyls, hexachlorobenzene). 

Primary hepatocellular carcinoma (PHC) has also been linked to the chronic consumption of ethanol. However, PHC did not significantly correlate with ethanol intake in several large population studies undertaken in Western countries (Breslow and Enstrom, 1974 Kono and Ikeda, 1979 Hinds et aL, 1980). In these studies, this lack of evidence may be related to an insufficient number of individuals with PHC. It should also be noted that the diagnosis of PHC may be unreliable (Saracci and Repetto, 1980), and it is possible that more careful examination of cirrhotic livers would reveal a higher incidence of hepatocellular carcinoma. Other studies have shown a positive association between ethanol consumption and PHC. In the third National Cancer Survey, Williams and Horm (1977) found a suggestive dose-dependent association between ethanol consumption and PHC, while Hakulinen et aL (1974) reported a significant association between PHC and ethanol misuse in the Finnish population. 

More than ten most successful conjugates in animal experiments entered clinical trials with only one containing targeting moiety (PK2). The first two, PKl and PK2 (HPMA copolymer, enzymatically degradable GFLG spacer, bound Dox or galac-tosamine) entered clinical studies in the late 1990 s. The evaluation demonstrated properties superior free Dox as far as toxicity is concerned but, unfortunately, only partial responses were seen in breast, NSCLC (PKl) and primary hepatocellular carcinoma (PK2) patients and the evaluation was terminated after phase II of clinical testing. 

Maeda, T. Konno and D. J. Kerr, 1998, A novel dosage approach for evaluation of SMANCS [poly-(styrene-co- maleyl-half-n-butylate) - neocarzinostatin] in the treatment of primary hepatocellular carcinoma. 7nf. 7. Oncol. 12 1217-1223. 

Steel J, Baum A, Carr B (2004) Quality of life in patients diagnosed with primary hepatocellular carcinoma hepatic arterial infusion of Cisplatin versus 90-Yttrium microspheres (Therasphere). Psychooncology 13 73-79... 

Kanematsu T, Matsumata T, Shirabe K (1993) A comparative study of hepatic resection and transcatheter arterial embolization for the treatment of primary hepatocellular carcinoma. Cancer 71 2181-2186 Kawai S, Tani M, Okumura J, Ogawa M et al (1997) Prospective and randomized clinical trial of lipiodol-transcath-eter arterial chemoembolization for treatment of hepatocellular carcinoma a comparison of epirubicin and doxorubicin (second cooperative study). Semin Oncol 24 38-45... 

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