Mouse Model for Mesothelioma Reproduces Human Disease

According to an article on mesothelioma research, scientists have established a mouse model for human malignant mesothelioma that will provide valuable insight into cancer development and progression along with new directions for design of therapeutic strategies. The research, published by Cell Press in the March issue of Cancer Cell, may eventually lead to a substantially improved outlook for patients with this devastating disease.

Chemotherapy can sometimes lead to improvement of overall survival but there is no cure for malignant mesothelioma and patients often succumb from the disease within a year of diagnosis. "There is an urgent need for experimental models of malignant mesothelioma that can be used to not only study the onset and progression of the disease, but also to serve as a model to select new combination therapies and targeted agents," says study leader, Dr. Anton Berns, from The Netherlands Cancer Institute.

In humans, malignant mesothelioma has been associated with genetic lesions that result in the loss of Neurofibromatosis type 2 (NF2) and genetic lesions affecting RB and P53 pathways. Dr. Berns' team investigated whether a range of conditional single or compound mutations in the Nf2, p53 and Rb pathways within the mesothelial lining of the thoracic cavity would cause malignant mesothelioma in mice.

The researchers found that the vast majority of mice with conditional Nf2;Ink4a/Arf and Nf2;p53 mutations developed MM after a short latency period. The mouse malignant mesothelioma tumors, which could be followed noninvasively through the use of bioluminescence imaging, closely resembled human MM. Interestingly, Nf2;Ink4a/Arf knockout mice had a more invasive cancer when compared with Nf2;p53 knockout mice. The researchers went on to show that the loss of Ink4a makes a substantial contribution to the poor clinical outcome of murine malignant mesothelioma.

These results describe an excellent model system for investigating the molecular mechanisms that underlie malignant mesothelioma . "Our mouse models should be suitable to further dissect pathways critically important in mesothelioma development and progression and serve as invaluable tools to test new intervention strategies," concludes Dr. Berns. "We have also derived a series of cell lines that reproduce the disease when grafted into the thoracic cavity. These may also facilitate design of better MM therapies."

Useful asbestos website

The Department of Health and Human Services has a useful website with a great deal of information regarding asbestos, including what it is, types of asbestos exposure, health effects, what you can do if you’re exposed to it, FAQs, info on lung cancer and mesothelioma, plus a variety of links to other valuable resources.

W.R. Grace on verge of making legal history

According to an editorial on the Wall Street Journal’s website on asbestos and mesothelioma, W.R. Grace is on the verge of making legal history with a trial proceeding that could alter the federal asbestos bankruptcy landscape forever.

A building materials company, W.R. Grace was among the firms swept up in a second round of asbestos litigation in the late 1990s. Having chewed their way through asbestos manufacturers, trial lawyers went after companies that had only a marginal asbestos link. By blanketing these firms with an avalanche of claims they recruited, the tort bar pushed at least 30 of these second-tier players into bankruptcy.

The company entered Chapter 11 with some 120,000 pending claims. But Judge Fitzgerald allowed it to send a medical questionnaire to those plaintiffs, and to request proof of a claim. Some 35,000 didn't bother to finish that process.

The vast majority of asbestos claims are bogus. The plaintiffs lawyers know it, which is why, instead of trying to defend these claims, they've fought every attempt by Grace to examine them. Now that they've lost that battle, they argue that because Grace settled such claims in the past, they should continue to pay them going forward.

If Judge Fitzgerald does discount most of these claims, it could mark the beginning of the end of the bankruptcy racket. Other judges will find it difficult to ignore the evidence and procedures here. As important, trial lawyers might be reluctant to push more companies (in asbestos or other mass torts) into bankruptcy court if they think false claims may be exposed.

This clean-up would obviously come too late for the dozens of companies that have already surrendered to asbestos trusts now run by the tort bar. But it's encouraging that courts are finally investigating sham asbestos claims. It's never too late for real justice.

Mesothelioma Q & A

Here is a short version of a Q & A from the National Cancer Institute’s website, with some useful answers to questions readers may have about mesothelioma, asbestos and health-related risks...

Mesothelioma is a rare form of cancer in which malignant (cancerous) cells are found in the mesothelium, a protective sac that covers most of the body’s internal organs. Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles.

1. What is the mesothelium?
The mesothelium is a membrane that covers and protects most of the internal organs of the body. It is composed of two layers of cells: One layer immediately surrounds the organ; the other forms a sac around it. The mesothelium produces a lubricating fluid that is released between these layers, allowing moving organs (such as the beating heart and the expanding and contracting lungs) to glide easily against adjacent structures.

2. What is mesothelioma?
Mesothelioma (cancer of the mesothelium) is a disease in which cells of the mesothelium become abnormal and divide without control or order. They can invade and damage nearby tissues and organs. Cancer cells can also metastasize (spread) from their original site to other parts of the body.

3. How common is mesothelioma?
Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. About 2,000 new cases of mesothelioma are diagnosed in the United States each year. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age.

4. What are the risk factors for mesothelioma?
Working with asbestos is the major risk factor for mesothelioma. A history of asbestos exposure at work is reported in about 70 percent to 80 percent of all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. Smoking does not appear to increase the risk of mesothelioma. However, the combination of smoking and asbestos exposure significantly increases a person’s risk of developing cancer of the air passageways in the lung.

5. Who is at increased risk for developing mesothelioma?
Initially, the risks associated with asbestos exposure were not known. However, an increased risk of developing mesothelioma was later found among shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople.

Today, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure in the workplace. People who work with asbestos wear personal protective equipment to lower their risk of exposure. The risk of asbestos-related disease increases with heavier exposure to asbestos and longer exposure time. However, some individuals with only brief exposures have developed mesothelioma.

On the other hand, not all workers who are heavily exposed develop asbestos-related diseases. There is some evidence that family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases.

6. What are the symptoms of mesothelioma?
Symptoms of mesothelioma may not appear until 30 to 50 years after exposure to asbestos. Shortness of breath and pain in the chest due to an accumulation of fluid in the pleura are often symptoms of pleural mesothelioma. Symptoms of peritoneal mesothelioma include weight loss and abdominal pain and swelling due to a buildup of fluid in the abdomen. Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever.

If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face. These symptoms may be caused by mesothelioma or by other, less serious conditions. It is important to see a doctor about any of these symptoms. Only a doctor can make a diagnosis.

7. How is mesothelioma diagnosed?
Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient’s medical history, including any history of asbestos exposure. A complete physical examination may be performed, including x-rays of the chest or abdomen and lung function tests. A CT (or CAT) scan or an MRI may also be useful. A biopsy is needed to confirm a diagnosis of mesothelioma.

8. How is mesothelioma treated?
Treatment for mesothelioma depends on the location of the cancer, the stage of the disease, and the patient’s age and general health. Standard treatment options include surgery, radiation therapy, and chemotherapy. Sometimes, these treatments are combined.

9. Are new treatments for mesothelioma being studied?
Yes. Because mesothelioma is very hard to control, the National Cancer Institute (NCI) is sponsoring clinical trials (research studies with people) that are designed to find new treatments and better ways to use current treatments. Before any new treatment can be recommended for general use, doctors conduct clinical trials to find out whether the treatment is safe for patients and effective against the disease. Participation in clinical trials is an important treatment option for many patients with mesothelioma.

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If you, a coworker or a family member has been exposed to asbestos, contact the law firm of LEVY PHILLIPS & KONIGSBERG, LLP. LPK has been a pioneer in representing victims of asbestos exposure, and is one of the nation’s premier law firms in the areas of toxic torts, product liability, personal injury, and discrimination law.