Category: Research

Penn Researchers Developing Protein ‘Passport’ To Help Deliver Cancer Drugs

• Nancy Meredith
• Cancer, Mesothelioma, Research, Treatments

The body’s immune system is designed to defend against bacteria, viruses and other perceived “foreign invaders” that assault the body. Unfortunately, the immune system doesn’t distinguish between harmful bacteria and friendly foreign objects such as medical devices implanted in a patient or nanoparticles used to deliver medicine to tumors. That poses complications to doctors trying to administer treatments to people with cancer, including malignant mesothelioma, a cancer caused by exposure to asbestos.

Doctors would like to avoid triggering an inflammatory response in cancer patients when they administer medicine or when implanting a pacemaker or artificial joint. Researchers at the University of Pennsylvania are experimenting with what they describe as “a passport” to allow therapeutic devices to get past the immune system, according to new research published in the journal Science.

The human body’s innate immune system responds to foreign bodies in a generalized way, trying to destroy anything it doesn’t recognize as a part of the body. The team of Penn researchers says the solution is to make the foreign particles seem like part of the body so the immune system doesn’t destroy them.

The researchers reported this week that they had accomplished that feat in lab mice, attaching customized protein fragments to foreign particles that tricked the animals’ immune system. The key was tricking the immune-system “border guards” known as macrophages that are a type of white blood cell that find and eat invaders. Macrophages continually monitor the bloodstream for a type of protein called CD47, a marker of self. If an object such as a red blood cell has CD47 on its membrane, the macrophages let it pass.

The Penn team leader, Dennis E. Discher, a professor of chemical and biomolecular engineering, compared CD47 to a passport that identifies a cell as part of the body rather than a foreign object. The research team attached fragments of CD47 to plastic nanoparticles, then injected them into laboratory mice. Nanoparticles, which are smaller than one-billionth of a meter, are useful in delivering, antibodies, drugs and imaging agents and are being studied for diagnosis and treatment of cancer, according to the National Cancer Institute.

The researchers said the technique enhanced the performance of nanoparticles carrying tumor-shrinking medicine and other loaded with dye to capture images of the tumors. They observed that the particles carrying a cancer drug Taxol were shrinking tumors in mice.

Discher said in an article in the Philadelphia Inquirer that the technique could be useful in overcoming resistance to much larger foreign objects in the body such as pacemakers and joint replacements.

Researchers not involved in the research called it a promising advance, though it will take some years before the technique is ready to use with human cancer patients.

Know more about mesothelioma and how you can deal with it.

World Health Organization Reiterates All Forms of Asbestos Cause Cancer

• Nancy Meredith
• Asbestos Exposure, International News, Mesothelioma, Research

The World Health Organization and the International Agency for Research on Cancer issued a joint statement Feb. 19 stating that all forms of asbestos cause cancer in humans and stopping the use of all forms of asbestos is the most efficient way to eliminate diseases caused by asbestos such as mesothelioma, a cancer of the lining of the chest and abdominal cavities.

The joint statement came in response to an article published this month in The Lancet medical journal raising questions about the IARC ‘s participation in a conference in Kiev, Ukraine and potential conflicts of interest. The IARC is participating with the Russian Scientific Research Institute of Occupational Health in a study of cancer among chrysotile workers in Asbest, Russia. The lead author of the research is Evgeny Kovalevsky, who is a promoter of chrysotile asbestos. The IARC is providing epidemiological expertise for the study.

Several prominent American health researchers including Richard Lemen, retired U.S. Assistant Surgeon General, sent a letter to the IARC saying it was unacceptable that a scientist who is a promoter of asbestos should be a lead investigator on an IARC research project. The authors of the letter noted that the World Health Organization had previously withdrawn the Russian Scientific Research Institute’s designation as a WHO collaborating center because of the institute’s conflicts of interest with the Russian asbestos industry.

In the joint statement, the WHO and IARC said the study on cancer among chrysotile asbestos workers in Asbest, Russia will provide important scientific data to quantify the risk of cancers known to be related to chrysotile, the most commonly produced asbestos fiber. In addition it may be useful in quantifying the risks of additional cancers suspected to be related to chrysotile asbestos exposure. The IARC acknowledged receiving a number of emails urging the agency not to participate in the conference.

The IARC and WHO said they take conflict of interest seriously and use a rigorous process to protect research.

According to the Lancet article, the timing of the IARC attendance at the conference and decision to collaborate in the study are particularly sensitive on the eve of an upcoming meeting of countries participating in the Rotterdam Convention. The attendees at the conference will discuss the listing of chrysotile to the Rotterdam Convention, which would require countries that import chrysotile asbestos to give prior informed consent of the health hazards it poses. Russia which has an active asbestos industry, may try to block the addition to chrysotile to the list of hazardous substances.

The heaviest burden of asbestos cancer is currently found in the United State, European countries, Australia, Japan and South Africa, according to a 2012 article in the British Journal of Cancer. The highest consumption of asbestos is in China, Russian, India, Ukraine, Thailand, Brazil and Iran, signaling that those countries will have increases in mesothelioma and asbestos-related cancer deaths in the future.

Approximately, 2,500 to 3,000 people in the U.S. die each year of mesothelioma. It is a devastating disease. Most people who are diagnosed with mesothelioma were exposed to asbestos in a workplace or during military service decades ago.

Sources :

• Lancet article
  http://secure.jbs.elsevierhealth.com/action/cookieAbsent
• joint statement
  http://www.who.int/mediacentre/news/statements/2013/response_lancet_20130219/en/

Researchers Assess Safety and Effectiveness of New Mesothelioma Drug

• Nancy Meredith
• Cancer, Mesothelioma, Research, Treatments

Medical researchers at Memorial Sloan-Kettering Cancer Center in New York have treated the first patient with a new experimental vaccinia virus-based cancer therapy designed for patients with malignant pleural mesothelioma or non-small cell lung cancer. Mesothelioma is a cancer of the lining of the chest cavity caused by exposure to asbestos.

Genelux Corp., a biopharmaceutical company that develops vaccinia virus-based cancer therapies, announced in a Feb. 6 press release the treatment of the first patient in the Phase I clinical trial designed to evaluate a drug known as GL-ONC1.

Vaccinia virus cancer therapies are part of an emerging area of medical research that utilizes modified viruses to target and destroy malignant cancer cells. Vaccinia virus produces a potent immune reaction to help destroy tumors. The virus was used extensively during the campaign to wipe out smallpox.

Through the current trial, the New York mesothelioma treatment researchers want to learn more about the safety and effectiveness of the new drug at different dosage levels on cancer patients with malignant pleural effusion. The accumulation of fluid between the thin layers of tissue lining the lung is known as pleural effusion. When the fluid contains cancer cells, it is known as malignant pleural effusion. A buildup of fluid is a complication that occurs in many patients who have pleural mesothelioma or lung cancer.

The clinical trial, which is recruiting patients, will assess the safety and tolerability of GL-ONC1 and the severity of side effects. The primary goal is to assess a safe dosage level. The trial may enroll up to 54 patients.

Dr. Valerie W. Rusch, a leading thoracic surgeon and expert on mesothelioma, is the lead researcher in the clinical trial sponsored by Memorial Sloan-Kettering Cancer Center.

“We are very pleased that researchers at MSKCC have initiated this important trial, “Dr. Aladar A. Szalay, founder and CEO of Genelux Corp., said in a press release. “For the first time, this will allow us to examine the feasibility and effects of administering GL-ONC1 directly into the chest cavity to some of the most aggressive cancers of the thoracic cavity—including mesothelioma and non-small cell lung cancer.”

Szalay said the drug has been well-tolerated and shown promising results in early trials involving human patients against a number of solid tumor cancers.

Mary Hesdorffer, executive director of the Mesothelioma Applied Research Foundation, an advocacy and support group, said novel therapeutic approaches based upon new scientific strategies may lead to more effective treatments and eventually a cure for mesothelioma.

Experimental Therapy Targets Mesothelioma Cancer Cells to Commit Suicide

• Nancy Meredith
• Cancer, Mesothelioma, Research, Treatments

 A frontier in treatment of mesothelioma and other cancers is the use of a type of gene therapy that induces cancer cells to self-destruct.

In a recent article in the Journal of Genetic Syndromes and Gene Therapy, Dr. Marek Malecki of the University of Wisconsin and Phoenix Biomolecular Engineering Foundation reports that cancer suicide gene therapy while not without risks remains one of the most promising experimental therapies for treating many types of cancer. Mesothelioma is a cancer of the lining of the chest cavity caused by exposure to asbestos.

The success of the gene therapy hinges on delivering the suicide genes to the cancer cells. That is accomplished by identifying unique or overabundant proteins that serve as flags of the invading army of malignant cancer cells, giving away their location. Researchers have identified a number of biomarkers that may serve as chemical signals of malignant mesothelioma cells.

The identification of biomarkers allows doctors to deliver therapeutic drugs with more precision, avoiding collateral damage to healthy cells. Chemotherapy drugs by comparison affect all cells and have side effects including nausea and toxicity. Surgery to remove operable mesothelioma tumors inevitably removes healthy tissue as well as cancerous tissue and affects a patient’s quality of life.

That is why targeted therapies such as suicide gene therapy hold promise. To induce cancer cells to self-destruct, doctors inject a genetically modified virus into the tumor to deliver the suicide genes which prompts them to produce a special enzyme. The patient then receives another drug that transforms the enzyme into a toxic compound that prompts the rapidly dividing cancer cells to commit suicide.

Researchers have observed promising results of suicide gene therapy in initial clinical trials involving mesothelioma and other types of cancer. While the treatment has not yet been approved by the Food and Drug Administration, it holds the potential to eliminate cancer cells without harming healthy cells, minimizing side effects suffered by patients.

For Patients With Mesothelioma, Thirteen Relevant Facts About Asbestos Disease in 2013

• Nancy Meredith
• Asbestos Exposure, Cancer, Research, Treatments

A group of nine doctors from New York University, the University of Hawaii and other research universities who specialize in treating mesothelioma patients discussed facts, theories and myths about mesothelioma in an article in the Journal of Cell Physiology, a peer-reviewed scientific journal. Their findings, made available online in January 2013, are well worth revisiting at the outset of the new year.

Here are 13 bold points from  the article:

• More than 20 million people in the United States are at risk of developing malignant mesothelioma due to asbestos exposure.
• The duration and intensity of an individual’s exposure to asbestos are important variables affecting the likelihood of development of asbestos disease.
• All studies agree that the incidence of mesothelioma among men has continued to rise during the last five decades, while the incidence among women has remained relatively flat. More than 100,000 U.S. citizens are expected to die of mesothelioma during the next 40 years.
• The development of mesothelioma is related to the chronic inflammatory process caused by the presence of microscopic asbestos fibers in the chest cavity.
• Development of malignant mesothelioma has been associated with commercial use of asbestos in the early and mid 20^th century. Prior to the 1950s, malignant mesothelioma tumors were extremely rare.
• Today, malignant mesothelioma is responsible for approximately 2,500 to 3,000 deaths per year in the United States and approximately 5,000 deaths in Western Europe.
• It’s a myth that asbestos has been banned in commercial products in the United States. Countries in the European Union have banned asbestos use, but not the U.S. The continued import of products containing asbestos in the U.S. and potential exposure to asbestos in place means workers exposed to the mineral fibers will continue to be at risk of developing mesothelioma.
• It’s a myth that malignant mesothelioma will soon disappear because of reduced use of the product. The rate of malignant mesothelioma has remained constant since 1994 and is increasing in some countries.
• It’s a myth that mesothelioma is a slow growing tumor. Mesothelioma grows aggressively once the cancer develops and most likely produces clinical symptoms within a few years. There is a long latency period of 20 to 70 years  between initial exposure to asbestos fibers and the development of mesothelioma. The distinction is important. The latency period appears to be influenced by the amount of exposure. Workers in trades with higher exposure to asbestos may have shorter latency periods before the cancer develops.
• Due to the long latency period, researchers estimate that mesothelioma mortality rates will continue to increase 5 to 10 percent per year in most industrialized countries for the next two to three decades despite efforts to get rid of asbestos. In the U.S, the number of mesothelioma deaths is likely to exceed 3,000 per year. Approximately 20 to 25 percent of deaths due to mesothelioma in the U.S. are misattributed to other causes.
• A mesothelioma patient’s survival is influenced by the stage of the cancer upon treatment.
• Stage I is the localized cancer while Stage IV describes advanced cancer that has spread beyond the point of origin. Among 663 patients who underwent surgical procedures for mesothelioma from the 1990 through 2006, the median survival was:
• Stage I mesothelioma — 38 months median survival
• Stage II mesothelioma—19 months
• Stage III mesothelioma—11 months
• Stage IV mesothelioma—7 months
• It’s expected that development of reliable blood tests that can lead to earlier detection of mesothelioma before it has advanced to stage III or IV will increase the percentage of patients who are candidates for surgery and increase overall survival.