Index Ranks Drug Makers Worldwide On Efforts To Make Medicines Available In Developing Countries

European pharmaceutical companies surpass their U.S. counterparts in making their medicines available and affordable to developing countries, according to an index released on Monday that ranks drug makers based on their corporate responsibility, the Financial Times reports (Jack, Financial Times, 6/15). The list, called the Access to Medicine Index, was created for “social responsibility” funds and investors who want to know how drug makers are helping people with HIV/AIDS, malaria, tuberculosis and other diseases prevalent in the developing world, according to the New York Times (McNeil, New York Times, 6/17).

Produced by the Netherlands-based Access to Medicine Foundation, the ranking is based on eight main criteria, including companies’ policies on increasing drug access, patents, research into neglected diseases and pricing systems. The United Kingdom’s GlaxoSmithKline topped the list, followed by Denmark’s Novo Nordisk in second place and the U.S.’ Merck in third. Pfizer, the world’s largest drug maker, ranked 17th, and there were no Japanese drug companies on the list. India-based generic companies Ranbaxy Laboratories and Cipla also were on the list.

Wim Leereveld, head of the Access to Medicine Foundation, said the index will provide investors with the resources to assess companies’ social responsibility and “prompt laggards into actions.” In terms of the gap between European and U.S. companies, Leereveld said it is largely cultural. “Europe is closer to Africa and has deeper relations with Africa,” he said, adding, “But it is also clear from issues like carbon emissions and climate change that there is something of a transatlantic divide on corporate social responsibility issues” (Hirschler, Reuters, 6/16). However, Leereveld said he hopes the index will make some companies “shining examples to others” and be useful to governments, medical charities and journalists (New York Times, 6/17).

Some long-term investors are concerned that the index could have a negative impact on drug makers’ reputations and operations if they fail to focus on providing access to medicines in developing countries, Reuters reports (Reuters, 6/16). However, a group of fund managers who endorsed the index in a statement said there is a need for tools that help investors and analysts assess the long-term investment value of companies, including how they respond to the issue of access to medicine (Financial Times, 6/15).

Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation.

© 2008 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

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HIV/AIDS Cases In China Increased By 3,000 Monthly From January 2006 To June 2007, Official Says

The number of HIV/AIDS cases on mainland China increased by an average of 3,000 monthly between January 2006 and June 2007, Wang Ning, deputy director of the Chinese Center for Disease Control and Prevention, said Monday, China Daily reports.

Wang added that 32,235 new HIV/AIDS cases have been recorded so far this year and that about 3,000 people have died of AIDS-related causes since January. At the end of June, HIV/AIDS cases had been reported in 74% of counties throughout China. Guangdong, Guangxi, Henan, Xinjiang and Yunnan provinces accounted for 76% of all HIV/AIDS cases nationwide, while Anhui, Guangxi, Henan, Hubei and Yunnan provinces accounted for 83% of all AIDS cases nationwide, China Daily reports (Chen, China Daily, 11/6).

About 38% of new HIV diagnoses were transmitted sexually, an increase of 30% from last year, Wang said (Reuters, 11/5). In addition, about 3% of new cases were transmitted among men who have sex with men. Although the number of new HIV/AIDS cases among high-risk groups, such as injection drug users and commercial sex workers, has decreased, the general population is at higher risk, in part because of risky sexual behaviors, Wang added (China Daily, 11/6).

About 220,000 people nationwide were living with HIV/AIDS at the end of September, and 25% of those had developed AIDS, Wang said. UNAIDS has estimated that about 650,000 people in China are living with HIV/AIDS, Reuters reports (Reuters, 11/5).

Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

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Immune System Suppression Studied By Scripps Research Team

The work was reported in the October 16 issue of the journal Cell Host & Microbe.

The study described the suppression of this immune response in mice infected with lymphocytic choriomeningitis virus, pointing to potential new avenues for the development of drug treatments for immunosuppressive diseases in humans.

“It’s the first demonstration that a virus causes suppression of the interferon response in vivo,” says the paper’s senior author Michael Oldstone, a Scripps Research professor and a pioneer in immune system studies. “This model explains how a secondary infection can be caused by a normal virus infection and this provides the guide for what to do and where to look in human diseases, which are of course more difficult.”

Mammals have two main ways to fight off infections. Adaptive immune responses are those that involve the production of antibodies and T lymphocytes that attack specific infections. In contrast, innate immune responses are genetically encoded and are generally the same regardless of infection type. One key component of the innate immune system is interferon, which plays a range of roles including direct antiviral effects, activating innate natural killer cells and adaptive T lymphocytes, which destroy a wide range of infectious invaders.

To better understand this system, the Scripps Research team, spearheaded by Elina Zuniga, formerly a postdoctoral fellow in the Oldstone lab who is now assistant professor at the University of California, San Diego, worked with mice infected with lymphocytic choriomeningitis virus, a model Oldstone describes as a Rosetta Stone for understanding viral pathogenesis and immune system recognition of foreign substances like microbes and viruses. The researchers found that the virus suppressed the mouse immune system by interacting with immune cells known as plamacytoid dendritic cells, which are key producers of one of two critical groups of interferons, known as type I.

When plasmacytoid dendritic cells come in contact with viruses and other foreign invaders, they bind with them via membrane proteins known as toll-like receptors. Under normal conditions, this binding triggers massive production of type I interferon that then triggers other immune responses.

But the lymphocytic choriomeningits virus, and presumably other immunosupressor viruses like measles and HIV, disable this system. This then compromises other reactions, most critically activation of the natural killers that would otherwise destroy the virus-infected cells, as well as other invaders.

The researchers showed that once in this infected condition, a secondary opportunistic agent, in this case the herpes virus murine cytomegalovirus, which the mice could have otherwise fought off, grew unchecked. Remarkably, opportunistic infections with herpes viruses are frequently observed in patients infected with HIV and the mechanism described in this study could well be one of the underlying causes.

One critical aspect of the group’s findings is that while the initial lymphotcytic choriomeningitis virus effectively blocked interferon production, it did not kill the dendritic cells, instead allowing them to function as long-term hosts. This allows such viruses to persist, causing persistent immunosuppression.

“I think the implications are that many of the diseases we don’t know the causes for, be they behavioral, mental, cardiovascular, or endocrine, may well be caused by viruses that persist without destroying the differentiated cells they infect, alter their functions, and by this means alter homeostasis and cause disease,” says Oldstone. “Examples would be viruses that persistently infect neurons and cause problems in learning and behavior, viruses that infect oligodendrocytes and cause demyelination, and viruses that infect endocrine cells and alter their production of hormones. There may be some differences, but most certainly there are a lot of commonalities.”

Oldstone says that knowing such basic details about how a virus can suppress the mouse immune system could well aid the development of new treatments for the many immunosuppressive conditions such as HIV and measles that plague humans. “I think that our study opens up an avenue for people who work in those human diseases to translate our findings,” says Oldstone.

For now, Oldstone’s group is focused on identifying the signals and molecules involved in the lymphocytic choriomeningitis virus’s crippling of the dendritic cells’ interferon production.

###

In addition to Oldstone and Zuniga, the authors of the study, titled “Persistent virus infection inhibits type I interferon production by plasmacytoid dendritic cells to facilitate opportunistic infections,” are Li-Ying Liou, and Marilyn Mendoza, from The Scripps Research Institute, and Lauren Mack, who is a master’s of science student at the Zuniga laboratory at UCSD.

This work was funded by grants from the National Institutes of Health and a Pew Foundation Latin American Fellowship that supported Zuniga during her time at Scripps Research.

About The Scripps Research Institute

The Scripps Research Institute is one of the world’s largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Currently operating from temporary facilities in Jupiter, Scripps Florida will move to its permanent campus by 2009.

Source: Keith McKeown

Scripps Research Institute

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Charity Action Duchenne Combines Social Networking With E-commerce For Innovative New Website

Action Duchenne, the Duchenne Muscular Dystrophy Charity, has launched its new website which combines the best in Web 2.0 technologies including social networking, wikipedia, blogging and micro-blogging. The new site Action Duchenne also enables the charity to take donations from registered members and the general public. Users may also create their own sponsorable events with donations going directly to Action Duchenne.

Nick Catlin, CEO of Action Duchenne commented, “We set up Action Duchenne eight years ago to provide support and education for families affected by Duchenne Muscular Dystrophy, and to raise money to find a cure. While we are closer to finding that cure, there is still a way to go, and in the meantime families find the help and support offered by our Duchenne community very comforting.’ Nick continued “Our new website has been designed to provide that interactive community so that families living with Duchenne can communicate more freely, share information about fund raising events, find information, we have a whole library of articles and papers many eminent scientists and people can donate those all important funds to help us continue our working in finding a cure for this most cruel of conditions.”

Duchenne Muscular Dystrophy affects 1 in 3,500 male births in the UK, and is the most common and severe type of muscular dystrophy – sufferers are diagnosed usually by the age of 5. Patients with DMD and Becker Muscular Dystrophy (BMD) are boys and young men who lack dystrophin, a protein that is critical to the structural stability of muscle fibres. Patients develop progressive muscle weakness. Duchenne affects all muscles including the heart and respiratory system leaving young people paralysed by late teens and many patients do not live past their twenties.

The new website provides a wealth of information about Duchenne, what causes it and the current treatments, about campaigns, education and inclusion programmes, fund raising events, blogs, conferences and news. As well as this registered users can set up their own Stop Wasting web page, post pictures, post their own news, network with friends, blog and micro-blog and generally interact in the same was as on sites like Facebook and Twitter. The site also includes a Donations facility and an online store for Duchenne and Stop Wasting merchandise.

Anton Faulconbridge, Director of Rantmedia who built the site said, “We are delighted to continue our relationship with Action Duchenne on this very exciting project. Our ‘eCharity’ platform, with its full social networking, wiki-knowledgebase, e-commerce shop and user events has given Action Duchenne a cutting edge website that provides visitors with a complete community in which to share, interact and fund raise.”

Carl Tilson, aged 22, living with Duchenne and an active campaigner for the charity commented, “The new website is great. Social networking is the way forward and is an advantage when your mobility is severely restricted. It enables me to interact and keep in touch with my fellow soldiers in the Duchenne community.” Carl continued “Having such an interactive website will assist the charity making that much needed awareness worldwide and great awareness will then guide us into a new beginning, a fresh start and will finally lead us into victory against this monstrous disease”

Source
Action Duchenne

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California Gov. Schwarzenegger Should Sign Bill Allowing Condom Distribution In Prisons To Prevent Spread Of HIV, Editorial Says

Despite “laws forbidding” sex between prison inmates and prison officials’ denial that it occurs, inmates do have “unprotected sex,” making “prisons prime settings for the spread of deadly bloodborne viruses like hepatitis C and HIV,” a New York Times editorial says. CDC last year “underscored this point” when it “urged states without condom-distribution programs to think about starting them as a way of preventing the spread of HIV behind bars,” according to the editorial. It adds that by “protecting the inmates, the state would also protect the all-too-vulnerable wives and lovers to whom they inevitably return when their sentences are completed.”

The California Legislature last year “tried to take” CDC’s advice by “passing a landmark bill that would have allowed public health agencies to enter prisons and distribute condoms to inmates who wanted them,” the Times says. Although the bill had the “overwhelming support of the voting public,” Gov. Arnold Schwarzenegger (R) vetoed it and used the “familiar know-nothing excuse that handing out condoms would justify illegal sexual activity,” according to the editorial. The “experience of jurisdictions that allow condoms does not support this view,” the Times says, adding that “public health officials now recognize that condom-distribution programs are integral to any meaningful AIDS prevention program.” Such programs are operating in prisons in Canada, in much of the European Union and in jails in Los Angeles, New York City, Philadelphia, San Francisco and Washington, D.C., according to the editorial.

The California Legislature again has “taken up the condom bill,” which is sponsored by Assembly member Sandre Swanson (D), the editorial says, adding that the bill “deserves to pass the legislature, just as it did last year.” However, this time, Schwarzenegger should “sign the bill,” the Times says, concluding that it would “give California’s public health community a powerful tool to fight the spread of a deadly disease” (New York Times, 7/18).

“Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

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Euroscience Calls For Support For Convicted Health Workers In Libya

Euroscience calls on other academic and scientific organisations to protest at the conviction of six foreign medical workers, by a Libyan court of conspiring to deliberately inject 426 Libyan children with HIV virus.

On December 19, 2006 six foreign medical workers, Kristiyana Valtcheva, Nasya Nenova, Valentina Siropulo, Valya Chervenyashka, Snezhana Dimitrova and Ashraf al-Hajuj were convicted and sentenced to death by firing squad by a Libyan court. The six health workers were accused of conspiring to deliberately inject 426 Libyan children with HIV virus. This is the second time that a Libyan court has sentenced the 6 health workers to death: an earlier death sentence was overturned by the Libyan Supreme Court in 2005.

Euroscience is a grass-roots organisation which representing European scientists of all disciplines. Professor Enric Banda, President of Euroscience in calling for a reaction from all scientists said, “It is a tragedy that children have been infected by HIV virus at a hospital in Libya, but it is against justice to accuse a group of health workers for this incident when strong scientific evidence shows that they could not be responsible for the origin of this infection”.

A scientific report presented by some of the world most prominent experts in HIV, Professor Luc Montagnier and Prof. Vittorio Colizzi proves that the HIV was already present in Libya in 1997, long before the Bulgarian health workers arrived, pointing at poor hygiene at the hospital as the real cause of the infections. Other scientific data published online by Nature, 6 December, 2006 and backed by international forensic experts also present a firm alibi for the six medical workers facing the death penalty in Libya.

Euroscience asks other academic and scientific organisations to react fast against this injustice by public statements in national and international media or by writing directly to: His Excellency Mu’ammar al-Gaddafi, Leader of the Revolution, Office of the Leader of the Revolution, Tripoli, Libya.

EUROSCIENCE
8 rue des Ecrivains
F-67000 Strasbourg
Euroscience/

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Researchers Induce HIV-Neutralizing Antibodies That Recognize HIV-1 Envelope Protein, Lipids

For the first time, researchers have experimentally induced antibodies that neutralize HIV-1 and simultaneously recognize both HIV-1 envelope protein and lipids. The results were reported by U.S. Military HIV Research Program (MHRP) researchers on Aug. 25 in the online version of AIDS, the official journal of the International AIDS Society.

The lead investigators, Dr. Gary Matyas and Dr. Carl Alving, researchers in the Division of Retrovirology, MHRP, Walter Reed Army Institute of Research (WRAIR), and their collaborators, conducted the exploratory study using small synthetic HIV-1 peptides encapsulated in liposomes containing lipid A as an adjuvant.

The monoclonal antibodies, produced after immunizing mice, have binding characteristics that look similar to two well-known broadly neutralizing human monoclonal antibodies, known as 2F5 and 4E10, which also bind to HIV-1 protein and lipid. These antibodies, 2F5 and 4E10, are widely viewed as models of the types of neutralizing antibodies that might be useful in an effective HIV-1 vaccine. Until now, the HIV field has been unable to induce neutralizing antibodies that have both protein-binding and lipid-binding characteristics similar to 2F5 or 4E10. This study employed widely used, clinically acceptable, well-tolerated and relatively inexpensive generic antigen-adjuvant constituents that potentially could be used as part of a human formulation.

Dr. Carl Alving, Chief of the Department of Adjuvant and Antigen Research, said, “Some of the strongest naturally occurring antibodies that broadly neutralize HIV have the unique characteristics of recognizing both HIV protein and lipid. It has been believed that it might be difficult to induce such antibodies experimentally, and historically, this has been considered a potential roadblock to creation of an effective HIV vaccine. This study demonstrates that such antibodies might be induced with immuno-stimulating liposomes.”

Source:
Lisa Reilly

Henry M. Jackson Foundation for the Advancement of Military Medicine

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FDA Confirms E. Coli O157:H7 In Prepackaged NestlГ© Toll House Refrigerated Cookie Dough

Today, the U.S. Food and Drug Administration announced that it has found E. coli O157:H7 (a bacterium that can cause serious food borne illness) in a sample of prepackaged NestlГ© Toll House refrigerated cookie dough currently under recall by the manufacturer and marketer, NestlГ© USA. The contaminated sample was collected at NestlГ©’s facility in Danville, Va. on June 25, 2009.

On June 19, the FDA and the U.S. Centers for Disease Control and Prevention warned consumers not to eat any varieties of prepackaged NestlГ© Toll House refrigerated cookie dough due to the risk of contamination with E. coli O157:H7. The warning was based on an epidemiological study conducted by the CDC and several state and local health departments. As of Thursday, June 25, the CDC reports that 69 persons from 29 states have been infected with the outbreak strain. Thirty-four persons have been hospitalized, nine with a severe complication called hemolytic uremic syndrome. No one has died.

Further laboratory testing is needed to conclusively link the E. coli strain found in the product to the same strain that is causing the outbreak.

NestlГ© USA has fully cooperated with the FDA and CDC investigation and has recalled all of its prepackaged NestlГ© Toll House refrigerated cookie dough products.

For answers to consumer questions about this recall and warning, go to: fda/Food/ResourcesForYou/Consumers/ucm168346.htm.

For more information about E. coli, visit the CDC Web site here.

Consumers who have additional questions about these products should contact NestlГ© USA consumer services at 1-800-559-5025 and/or visit its Web site at verybestbaking.

For a complete listing of NestlГ© USA recalled products go here.

Source
U.S. Food and Drug Administration

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Customized Virus Kills Brain Tumor Stem Cells That Drive Lethal Cancer

A tailored virus destroys brain tumor stem cells that resist other therapies and cause lethal re growth of cancer after surgery, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center reports in the Sept. 18 edition of the Journal of the National Cancer Institute.

“We have shown first in lab experiments and then in stem cell derived human brain cancer in mice, that we have a tool that can target and eliminate the cells that drive brain tumors,” says co senior author Juan Fueyo, M.D., associate professor in M. D. Anderson’s Department of Neuro Oncology. A request to launch a clinical trial of the virus, called Delta 24 RGD, is expected to go to federal regulators this month.

The virus was tested against the most aggressive brain tumor glioblastoma multiforme, which originates in the glial cells that surround and support neurons. It is highly resistant to radiation and chemotherapy and so invasive that surgery almost never eliminates it. Patients suffering from this malignant glioma live on average for about 14 months with treatment.

Fueyo and colleagues developed Delta-24-RGD to prey on a molecular weakness in tumors and altered the virus so it could not replicate in normal tissue. They showed in a JNCI paper in 2003 that the virus eliminated brain tumors in 60 percent of mice who received injections directly into their tumors. The virus spreads in a wave through the tumors until there are no cancer cells left, then it dies.

Since 2004 scientists have found that brain tumors are driven by haywire stem cells that replicate themselves, differentiate into other types of cells, and bear protein markers like normal stem cells.

“Research has shown that these cancer stem cells are the origin of the tumor, that they resist the chemotherapy and radiation that we give to our patients, and that they drive the renewed growth of the tumor after surgery,” Fueyo said. “So we decided to test Delta-24-RGD against glioma stem cells and tumors grown from them.”

The research team led by Fueyo, co-senior author Frederick Lang, M.D., professor in M. D. Anderson’s Department of Neurosurgery, and first author Hong Jiang, Ph.D., instructor in neuro-oncology, derived four brain tumor stem cell lines from four specimens of glioblastoma multiforme. All four lines exhibited the characteristics and protein signatures of stem cells. Delta-24 succeeded in killing all four types in the lab.

Next, the researchers grafted the stem cell lines into the brains of mice and treated the resultant tumors with injections of Delta-24-RGD. Untreated mice had a mean survival time of 38.5 days, while treated mice had a mean survival of 66 days. Two of the eight treated mice survived for 92 days, until the end of the experiment, with no neurological symptoms.

“It’s important in animal models to see improvement in survival in the majority of animals, but to have some be cured and survive a long time without neurological symptoms is very rare,” Fueyo said. “We have to be cautious, because an animal model doesn’t fully represent humans, but the tumors grown by these stem cells closely resemble the tumors we see in our patients, which is an exciting finding in itself.”

Tumors in other mouse models tend to be round and self contained, explains co senior author and Frederick Lang, M.D., professor in M. D. Anderson’s Department of Neurosurgery. Malignant tumors in patients are never round, they invade other tissues and delve deeply into the brain. The cancer stem cell derived tumors in these experiments have the irregular shape and invasive characteristics of their human counterparts.

“That similarity to the human tumor is encouraging,” Lang said. “And it’s also encouraging that we got basically the same results with Delta-24-RGD in this experiment that we got in our earlier experiment using other tumor models.”

A clinical quality version of Delta-24-RGD has been manufactured by the National Cancer Institute and an independent consultant has completed a toxicology assessment. An Investigational New Drug Application to proceed with a phase I clinical trial is expected to be filed with the U.S. Food and Drug Administration in September. A clinical trial could began as early as this fall.

Delta-24-RGD exploits the fact that a protein called retinoblastoma (Rb) is either missing or defective in brain tumors. Rb normally guards against both the proliferation of cancerous cells and against viral infection. So the virus has an easier time invading tumors and replicating in its cells. Adenoviruses attacking normal cells employ their own protein, E1A, to counteract retinoblastoma’s defensive measures. To keep Delta-24-RGD out of normal cells, Fueyo and colleagues deleted a small part of the gene that produces E1A.

The JNCI paper shows that Delta-24 RGD forces tumor cells to devour themselves until they die. This self-cannibalization, called autophagy, occurs when a cell forms a membrane around part of its cytoplasm or an organelle and then digests the contents, leaving a cavity. A cell that dies from autophagy is riddled with cavities.

Cells normally employ autophagy temporarily to survive when nutrients are short, to recycle components to form new organelles, or to fend off viral or bacterial infection. In cancer research, there is evidence both that autophagy is a form of programmed cell death triggered to prevent the replication of damaged cells and that cancer cells in some instances employ it to survive attack.

“Our next experiments will address whether the cell kills itself or dies defending itself against the virus,” Fueyo says. Sure, the cell dies either way, but the distinction is important, Fueyo says, because the virus could be redesigned to either fuel or block autophagy to make it more effective. The autophagic protein Atg5 is heavily expressed in the dead tumor cells, making it a potential biomarker of the virus’ effectiveness.

The National Cancer Institute funded this research.

Co-authors with Fueyo, Lang and Jiang are Candelari Gomez-Manzano, Hiroshi Aoki, Marta Alonso, Seiji Kondo, Jing Xu, Yasuku Kondo, and Howard Colman, all of the M. D. Anderson Brain Tumor Center; B. Nebiyou Bekele, of M. D. Anderson’s Department of Biostatistics; and Frank McCormick, Cancer Research Institute and Comprehensive Cancer Center, University of California, San Francisco. Aoki also is affiliated with the Department of Neurosurgery, Brain Research Institute, Niigata University in Niigata, Japan.

University of Texas M. D. Anderson Cancer Center
1515 Holcombe Blvd., Box 229
Houston, TX 77030
United States
mdanderson

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Increased Risk Of Kaposi’s Sarcoma In Marijuana Users

The major active component of marijuana could enhance the ability of the virus that causes Kaposi’s sarcoma to infect cells and multiply, according to a team of researchers at Harvard Medical School. According to the researchers, low doses of ‘-9 tetrahydrocannabinol (THC), equivalent to that in the bloodstream of an average marijuana smoker, could be enough to facilitate infection of skin cells and could even coax these cells into malignancy.

While most people are not at risk from Kaposi’s sarcoma herpes virus (KSHV), researchers say those with lowered immune systems, such as AIDS patients or transplant recipients, are more susceptible to developing the sarcoma as a result of infection. Their findings, reported in the August 1 issue of Cancer Research, a journal of the American Association for Cancer Research, offer cautionary evidence that those with weakened immune systems should speak with their doctors before using marijuana medicinally or recreationally.

“These findings raise some serious questions about using marijuana, in any form, if you have a weakened immune system,” said lead study author Jerome E. Groopman, M.D., professor of medicine at Harvard Medical School. “While THC is best known as the main psychotropic part of marijuana, an analog of THC is the active ingredient of marinol, a drug frequently given to AIDS patients, among others, for increasing appetite and limiting chemotherapy-induced nausea and vomiting.”

While previous studies indicated that marijuana smoking was associated with Kaposi’s sarcoma, this is the first to demonstrate that THC itself can assist the virus in entering endothelial cells, which comprise skin and related tissue.

According to Dr. Groopman, the study illustrates the complicated role marijuana and other cannabinoids play in human health. Numerous types of cells display cannabinoid receptors on their outer surfaces, which act as switches that control cellular processes. Dr. Groopman’s laboratory had previously demonstrated that THC could have a protective effect against a certain form of invasive, drug-resistant lung cancer.

To study the combined effect of THC and KSHV, the researchers examined a culture of human skin cells, which are susceptible to infection and could provide a model of Kaposi’s sarcoma. These culture cells display many copies of two prominent cannabinoid receptors. Dr. Groopman and his colleagues found that by bonding to these receptors, low doses of THC activate two proteins responsible for maintaining a cell’s internal framework, or cytoskeleton. By altering the cytoskeleton, THC effectively opens the door for KSHV, allowing the virus to more easily enter and infect the cell. “We can take away that effect by using antagonists that block the two cannabinoid receptors, which adds evidence that THC is the culprit,” Dr. Groopman said.

Once a cell is infected, the presence of THC may also promote the cellular events that turn it cancerous, the researchers say. They found that THC also promotes the production of a viral receptor similar to one that attracts a cell-signaling protein called interleukin-8. Previous studies have noted that this receptor could trigger the cell to reproduce, causing Kaposi’s sarcoma-like lesions in mice. Indeed, the researchers saw that THC induced the infected cells to reproduce and form colonies in culture.

“Here we see both infection and malignancy going on in the presence of THC, offering some serious concerns about the safety of THC among those at risk,” Dr. Groopman said. “Of course, we still do not know the exact molecular events that are occurring here, but these results are just the first part of our ongoing research.”

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The study was funded by the National Institutes of Health.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries.

AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care.

AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Source: Greg Lester

American Association for Cancer Research

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