SAMe ( S-adenosylmethionine ) is Effective in Preventing Formation of Primary Liver Cancer in Rats

2009 study posted for filing

A new study investigated the effectiveness of S-adenosylmethionine (SAMe) in the prevention and treatment of hepatocellular carcinoma (HCC) or primary liver cancer. SAMe, a widely available nutritional supplement, with little known side effects, was found to be effective in preventing the formation of HCC in rats. However, high enough levels of SAMe were not attainable to successfully treat established HCC. The findings are available in the August issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases.

HCC is the fifth most common cancer and the third most frequent cause of cancer death worldwide. Risk factors for HCC include chronic infection with hepatitis B virus, hepatitis C virus (HCV), dietary aflatoxin, excessive alcohol use, cigarette smoking, diabetes and obesity. The overall 5-year survival for HCC patients is less than 10% and the disease rate is expected to rise due to the high prevalence of HCV in many areas of the world.

Shelly Lu, M.D., of the Keck School of Medicine at the University of Southern California, and colleagues studied the effects of SAMe on chemoprevention and treatment of HCC. In the U.S. the incidence of HCC doubled from 1979 to 1995 and the number of HCC cases for the following 20 to 30 years is projected to increase. “Given these projections, there is a tremendous interest in developing effective chemoprevention strategies,” said Dr. Lu. “And an important property of SAMe that makes it an attractive agent for chemoprevention and treatment of HCC is its ability to selectively kill liver cancer cells,” she added.

During the study researchers injected H4IIE cells into rats and found a 1cm tumor developed in the liver two weeks after injection. A regimen of IV SAMe was started one day after injecting the cells and continued for ten days. The researchers monitored the animals using MRI, ultrasound, and visual inspection to assess the liver tumors. “Treatment with IV SAMe by continuous infusion significantly reduced the tumor size and significantly prevented tumor development after 11 days,” researchers discovered.

Researchers found that if SAMe infusion was started after sizable tumors had already formed it failed to reduce the rate of tumor growth after 24 days of treatment. This is because of a compensatory response of the liver to metabolize SAMe and prevent its accumulation. “The observation that SAMe failed to exert any therapeutic effect in already established HCC is disappointing,” said Dr. Lu. “But whether SAMe can be effective in treating HCC in man remains unclear because this compensatory mechanism may not work properly in human HCC. Nevertheless, effectiveness of SAMe in chemoprevention of human HCC deserves study now.”

Grapefruit compound may help combat hepatitis C infection ” may be able to block the secretion of hepatitis C virus “

Contact: Sue McGreevey smcgreevey@partners.org 617-724-2764 Massachusetts General Hospital

MGH study reveals mechanism key to maintaining chronic infection, potential therapy target

A compound that naturally occurs in grapefruit and other citrus fruits may be able to block the secretion of hepatitis C virus (HCV) from infected cells, a process required to maintain chronic infection.  A team of researchers from the Massachusetts General Hospital Center for Engineering in Medicine (MGH-CEM) report that HCV is bound to very low-density lipoprotein (vLDL, a so-called “bad” cholesterol) when it is secreted from liver cells and that the viral secretion required to pass infection to other cells may be blocked by the common flavonoid naringenin.

If the results of this study extend to human patients, a combination of naringenin and antiviral medication might allow patient to clear the virus from their livers.  The report will appear in an upcoming issue of the journal Hepatology and has been released online.

“By finding that HCV is secreted from infected cells by latching onto vLDL, we have identified a key pathway in the viral lifecycle,” says Yaakov Nahmias, PhD, of the MGH-CEM, the paper’s lead author. “These results suggest that lipid-lowering drugs, as well as supplements, such as naringenin, may be combined with traditional antiviral therapies to reduce or even eliminate HCV from infected patients”

HCV is the leading cause of chronic viral liver disease in the United States and infects about 3 percent of the world population. Current antiviral medications are effective in only half of infected patients, 70 percent of whom develop chronic infection that can lead to cirrhosis or liver cancer.  Since the virus does not integrate its genetic material into the DNA of infected cells the way HIV does, totally clearing the virus could be possible if new cells were not being infected by secreted virus.

“Identifying the route by which HCV is released from cells introduces a new therapeutic target,” says Martin Yarmush, MD, PhD, director of the MGH-CEM and the paper’s senior author. “That pathway’s dependence on cholesterol metabolism could allow us to interfere with viral  propagation to other cells and tissues, using tools already developed for atherosclerosis treatment.”  Yarmush is the Helen Andrus Benedict Professor of Surgery and Bioengineering at Harvard Medical School (HMS).

Grapefruit’s bitter taste is caused the presence of the flavonoid naringin, which is metabolized into naringenin, an antioxidant previously reported to help lower cholesterol levels. Considerable research has suggested that HCV infects liver cells by, in essence, “hitching a ride” onto the natural lipoprotein-cholesterol metabolic pathway.  Since earlier evidence has shown that naringenin can reduce secretion of vLDL from liver cells, the researchers examined whether the compound might also lower HCV secretion from infected cells. Their experiments confirmed that naringenin does reduce the secretion of HCV from infected cell lines and showed that the compound inhibits the mechanism for secreting a specific lipoprotein that binds HCV.

“This work presents the possibility that non-toxic levels of a dietary supplement, such as naringenin, could effectively block HCV secretion,” says Raymond Chung, MD, MGH director of Hepatology and one of the study authors, “This approach might eventually be used to treat patients who do not respond to or cannot take traditional interferon-based treatment or be used in combination with other agents to boost success rates.”

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Chung is an associate professor of Medicine at HMS, and Nahmias is an instructor in Surgery and Bioengineering. Additional co-authors of the Hepatology paper are Jonathan Goldwasser, Monica Casali, PhD, Daan van Poll, MD, MGH-CEM; and Takaji Wakita, MD, Tokyo Metropolitan Institute. The work was supported by grants from the National Institutes of Health and Shriners Hospitals for Children.

Massachusetts General Hospital (www.massgeneral.org), established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.

Hepatitis A and or B Gives greater chance to recover from Hep C..Plus Morphine increases HCV Replication

Contact: Lixin Zhu wjg@wjgnet.com 86-108-538-1892 World Journal of Gastroenterology

Who will recover spontaneously from hepatitis C virus infection

More than 3% of world population is infected with hepatitis C virus (HCV). The outcome of HCV infections is either self recovery or chronic hepatitis, and many of the chronic infections will develop into liver cirrhosis or liver cancer. Since there is no cure for chronic hepatitis C, nor is there any approved vaccine for this virus, hepatitis C is currently a major health problem worldwide.

Twenty to fifty percent of HCV infected patients recovers spontaneously. The hepatitis C patients and their relatives like to know if his/her infection would fall into the category for self recovery.

A research article to be published on August 21 in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Mihm from Georg-August-Universität spent more than 8 years working with a cohort of 67 patients who spontaneously recovered from HCV infection. In addition to these, the researchers included a similar number of patients with chronic HCV infection. Large sample size allowed these investigators to obtain results with great statistical significance, and to draw very reliable conclusions.

One conclusion reported by the investigators is, patients who self recovered usually have lower levels of HCV antibody. Thus patients with lower HCV antibody titer may have a brighter clinical outcome. However, for a practical standard to be established to define a low HCV antibody titer, more effort is needed by investigators in the future.

Another interesting conclusion reached by these investigators is, co-infection by hepatitis B virus (HBV) is associated with a higher possibility of self recovery. The investigators suggested that the infection of HBV interferes with the HCV replication, which would finally lead to virus eradiacation.. HCV patients co-infected by hepatitis A virus also have a better chance of self recovery, possibly by a similar mechanism.

Active iv drug users are less likely to self recover, for a couple of reasons: 1, they have a higher incidence of re-infection; 2, drugs have been shown to inhibit the expression of antiviral cytokines such as IFN- and IFN-; 3, HCV replication has been shown to be enhanced both by morphine use and morphine withdrawal.

Several different genotypes of HCV were discovered. The HCV genotype studied by Dr. Milm¡¯s group is type 1b, which is the prevalent genotype in Germany, and in China.

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* Reposted on Request