Hepatocellular carcinoma: Epidemic and treatment

Allen, Jill N.; Venook, Alan P.

doi:10.1007/s11912-004-0047-9

Cited by 15 publications

(8 citation statements)

References 64 publications

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“…Individuals infected with hepatitis B or hepatitis C virus, and particularly those who subsequently develop cirrhosis, are at an increased risk of developing HCC [2,3]. The hepatitis virus is highly prevalent in developing countries, resulting in a very high incidence of HCC in these regions.…”

Section: Introductionmentioning

confidence: 99%

Expression and Functional Coupling of Liver β<sub>2</sub>-Adrenoceptors in the Human Hepatocellular Carcinoma

Kassahun¹,

Guenl²,

Ungemach

et al. 2012

Pharmacology

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Aim: Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of death worldwide. There are now multiple lines of evidence demonstrating that the β-adrenoceptor (β-AR) signaling plays an important role in the progression and metastasis of cancer and may become a novel target for cancer therapy. Little information exists regarding the status of β-ARs and their postreceptor intracellular signaling cascade in the development of human HCC. This study was conducted to detect the expression signal transduction of the β-ARs in liver membranes obtained from patients with HCC and elucidate their possible implication on HCC development. Methods: The β-AR density and subtype distribution were determined by receptor binding studies. Protein levels of the β₂-AR and G_s_α protein were determined by Western blot analysis. The receptor coupling efficiency and biochemical activities of the adenylate cyclase (AC) was also determined. Results: In HCC liver membranes, the β₂-AR density was higher than the density in the nonadjacent nontumor liver membranes. The β₂-AR protein expression was 1.5-fold increased as compared with nonmalignant controls, and positively correlated with the receptor density. The G_s_α protein expression as well as the receptor, AC and G protein-stimulated activation of the cAMP formation was reduced in HCC. Conclusion: The β₂-AR was upregulated in human HCC. Despite this upregulation of the receptor, there was an altered postreceptor signal transduction in HCC liver. The mechanisms responsible for this change in the growth of HCC and the nature of this alteration remain unclear.

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Section: Introductionmentioning

confidence: 99%

Expression and Functional Coupling of Liver β<sub>2</sub>-Adrenoceptors in the Human Hepatocellular Carcinoma

Kassahun¹,

Guenl²,

Ungemach

et al. 2012

Pharmacology

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“…It has been estimated that 17,550 new cases of liver cancer and 15,420 associated deaths will occur in the year 2005 in the United States alone (2). Many factors play a major role in the etiology of HCC; most important of them include hepatitis B and C viruses, alcohol, and aflatoxin exposure (1,3).…”

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confidence: 99%

Silibinin Efficacy against Human Hepatocellular Carcinoma

Varghese¹,

Agarwal

Tyagi³

et al. 2005

Clinical Cancer Research

128

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Purpose: Hepatocellular carcinoma (HCC) is one of the most common recurrent malignancies, for which, currently, there is no effective therapy. Considering the antihepatotoxic activity of silibinin, a widely used drug and supplement for various liver disorders, together with its strong preventive and anticancer efficacy against various epithelial cancers, we investigated the efficacy of silibin against human HCC cells. Experimental Design: Silibinin effects were examined on growth, cytotoxicity, apoptosis, and cell cycle progression in two different HCC cell lines, HepG2 (hepatitis B virus negative; p53 intact) and Hep3B (hepatitis B virus positive; p53 mutated). At molecular level, cell cycle effects of silibinin were assessed by immunoblotting and in-bead kinase assays. Results: Silibinin strongly inhibited growth of both HepG2 and Hep3B cells with a relatively stronger cytotoxicity in Hep3B cells, which was associated with apoptosis induction. Silibinin also caused G 1 arrest in HepG2 and both G 1 and G 2 -M arrests in Hep3B cells. Mechanistic studies revealed that silibinin induces Kip1/p27 but decreases cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)-2, and CDK4 levels in both cell lines. In Hep3B cells, silibinin also reduced the protein levels of G 2 -M regulators. Furthermore, silibinin strongly inhibited CDK2, CDK4, and CDC2 kinase activity in these HCC cells. Conclusion: Together, these results for the first time identify the biological efficacy of silibinin against HCC cells, suggesting the importance of conducting further investigations in preclinical HCC models, especially on in vivo efficacy, to support the clinical usefulness of silibinin against hepatocellular carcinoma in addition to its known clinical efficacy as an antihepatotoxic agent.

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“…In contrast with Asian populations, the percentage of Western patients with HCC but without underlying cirrhosis is considerable, and the development of HCC in cirrhotic individuals in the West is associated with a wider spectrum of underlying diseases. In the West, the percentage of virally engendered cirrhosis is lower than that in Asian regions, but alcoholtoxic or cryptogenic hepatic damage is observed more frequently in Western countries [14]. Thus, the etiologic pattern of HCC in Western regions of low risk for that disease differs appreciably from that in southeast Asia and sub-Saharan Africa.…”

Section: Risk Factorsmentioning

confidence: 94%

“…In Europe and North America, however, despite a significantly lower incidence rate of 3 to 4 per 100,000 population, a distinct increase in cases of HCC has been reported as a result of intravenous drug use, unsafe sexual practices, and other causes [13,14]. Because of a lack of effective HCV vaccination, underlying HCV infection is largely responsible for that increase.…”

Section: Risk Factorsmentioning

confidence: 99%

Current Management of Hepatocellular Cancer

2010

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Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, being the fifth most frequent cancer worldwide. It usually occurs in the setting of chronic liver disease and has a poor prognosis if untreated. Following the diagnosis, this disease requires multidisciplinary management. Orthotopic liver transplantation is theoretically the best treatment for early, unresectable HCC. However, the major practical obstacle is the extreme shortage of organs, which makes this a practical option only in selected patients. In this report we describe new advancements in diagnosis, classification, and treatment that have emerged in the field of HCC in recent years.

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Hepatocellular carcinoma: Epidemic and treatment

Cited by 15 publications

References 64 publications

Expression and Functional Coupling of Liver β<sub>2</sub>-Adrenoceptors in the Human Hepatocellular Carcinoma

Expression and Functional Coupling of Liver β<sub>2</sub>-Adrenoceptors in the Human Hepatocellular Carcinoma

Silibinin Efficacy against Human Hepatocellular Carcinoma

Current Management of Hepatocellular Cancer

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