Category: Research
Protein Linked to Tissue Inflammation Suggests New Approach To Treating Mesothelioma, University of Hawaii Researchers Say
Asbestos was used extensively at the Pearl Harbor shipyards during World War II and the decades afterward. Today, Hawaii has some of the highest rates of mesothelioma in the nation, according to cancer researchers at the University of Hawaii.
For more than a decade, researchers at the University of Hawaii Cancer Center have been deciphering the molecular processes that cause normal cells to tranform into malignant mesothelioma cells. In a study in the July issue of the scientific journal Cancer Research, they report that malignant mesothelioma relies on a particular protein known as HMGB1 to fuel the growth of tumors. Suppressing the protein may be key to a new approach for treating mesothelioma, which is notoriously difficult for doctors to manage.
Mesothelioma is a cancer of the lining of the chest and abdominal cavities. It develops from inhaling microscopic asbestos fibers that lodge in the thin tissue lining the body cavity causing inflammation that leads to cancer. People in jobs in which asbestos exposure is an occupational hazard such as mining, shipbuilding, maintenance, plumbing and electrical work have a higher incidence of asbestos-related disease.
Medical researcher Haining Yang, an assistant professor at the University of Hawaii, and colleagues have studied asbestos-related disease for more than a decade. In a series of research papers, the Hawaii cancer researchers have detailed how asbestos damages and kills cells through a process called programmed cell necrosis that leads to the release of a protein molecule called HMGB1.
Patients with mesothelioma have elevated levels of the protein in their blood. The researchers suggest the protein may play a critical role in transforming healthy mesothelial cells into cancer cells and fueling the growth of malignant tumors.
In the most recently published study, the researchers treated mice with malignant mesothelioma with antibodies aimed at suppressing the protein HMGB1. They observed that inhibiting HMGB1 reduced the growth of cancer cells and extended the lives of the mice. Their findings suggest that mesothelioma cells rely on HMGB1 and that removal of the protein may produce a therapeutic response in mesothelioma patients, suggesting a new approach for malignant mesothelioma treatment.
Mesothelioma takes the lives of about 3,000 people a year in the U.S. People typically develop mesothelioma symptoms 20 years to 50 years after exposure to asbestos. The incidence of mesothelioma has risen steadily in the last decade in some parts of the world, including Europe and China.
Research Focuses on Treatments That Target Mesothelioma Tumors
For 15 years, Dr. Raffit Hassan, a clinical oncologist at the National Cancer Institute, has been researching the protein mesothelin and its use in the treatment of mesothelioma. Mesothelioma is a cancer of the lining of the chest cavity and abdomen associated with exposure to asbestos.
A protein, mesothelin is present in normal tissue. But certain types of malignant tumors including mesothelioma express high levels of the mesothelin, making it a useful target for tumor-specific drugs. The ultimate goal of the National Cancer Institute is to develop new treatments for mesothelioma and other forms of cancer.
“Mesothelioma is not a very common disease, but it’s a tumor for which we really need to develop a good treatment,” Dr. Hassan said during a recent teleconference sponsored by the Meso Foundation, which provides information, research funding and advocacy for mesothelioma victims.
The first drug targeting mesothelin that Hassan has studied in clinical trials involving mesothelioma patients was Amatuximab, an experimental drug developed by Morphotek, a Pennsylvania company that develops cancer treatments. The treatment is an immunotoxin,a human-made protein that is designed to bind to cancer tumor cells, then inject toxins to kill them.
“I have been working on the same project for 10 years,” Dr. Hassan said. “I think we are starting to see some good results.”
The drug has been through phase I and II clinical trials and the results will be presented this summer. It has not yet been approved by the Food and Drug Administration.
The researchers are evaluating whether the drug when combined with chemotherapy drugs is more effective at controlling mesothelioma.
“The results show the drug is safe and there is activity,” Hassan said. “To be really sure the drug benefits patients we’ll need to do a randomized clinical trial. That will be the next step.”
Approximately 3,000 people are diagnosed with malignant mesothelioma each year. Most are older workers, retired workers and veterans were exposed to asbestos dust in the workplace or during military service. Symptoms of mesothelioma typically take 20 to 40 years to appear. But the cancer is aggressive and more effective treatments are needed to control the disease and extend the lives of mesothelioma patients.
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Gene Therapy Moves Scientists One Step Closer to a Mesothelioma Cure
Finding a cure for mesothelioma did not seem possible just several years ago. The asbestos-caused cancer is extremely aggressive, and the cancerous cells invade the lungs and spread throughout the body often rendering standard cancer treatments ineffective against the disease. However, with the recent advances in gene therapy, now being touted as the next frontier in medicine, there is new hope in the medical field that cures are on the horizon for patients with rare and incurable diseases such as mesothelioma.
Ricki Lewis, a New York-based geneticist and author, explores this “next frontier” in her latest book The Forever Fix. The book follows the journey of the use of gene therapy to restore the vision of a young boy who was nearly blind from a hereditary disorder. The doctors replaced the single defective gene in the New York boy’s eyes that prevented his eyes from using vitamin A to send visual signals to his brain. Once the defective gene was replaced, the boy’s vision was restored and no further treatments or surgery were required.
“The goal of gene therapy is to replace faulty instructions,” said Lewis, who has a Ph.D in genetics from Indiana University. “It’s not right for every disease. But it is an approach that can be considered some day along with drugs, surgery and everything else.”
Most rare diseases, of which there are nearly 7,000 in the United States, are caused by a single gene defect, making them better candidates for gene therapy, Lewis said. Cancers, however, are often caused by a combination of genes as well as environmental factors. In the case of mesothelioma, asbestos is known to cause the disease, but researchers now believe a person’s genetics may determine whether they will actually contract the disease.
Lewis points to a study led by Dr. Jill Ohar of Wake Forest University, first reported in Oct. 2009, where as part of a new mesothelioma clinical trial, her team is investigating whether a person’s genes increase the risk of developing mesothelioma. Ohar began her research when she found “that there is a strong tendency for mesothelioma to run in families and it tends to be associated with a family history of cancer, which suggests a genetic susceptibility.”
“Getting at the basis of why one person develops mesothelioma and another person doesn’t, that is going to hold a clue to really fighting it,” Lewis said. “Then we will know what to do the gene therapy on.”
Mesothelioma victims typically show disease symptoms years or even decades after exposure to asbestos in an industrial or manufacturing workplace. The disease is eventually fatal, but aggressive therapy may prolong the lives of patients who are diagnosed early. Hopefully soon, mesothelioma patients will enjoy long, productive lives through research on genetics.
Sources :
- The Forever Fix
http://us.macmillan.com/theforeverfix/RickiLewis - mesothelioma clinical trial
https://clinicaltrials.gov/ct2/show/NCT01590472?term=mesothelioma+and+genetics&rank=1
Enlisting the Body’s Immune System to Fight Mesothelioma and Asbestos Disease
Mesothelioma, a cancer of the lining of the lung and abdomen, suppresses the normal immune system response designed to ward off disease. Scientists have been trying to understand the mechanics of the immune suppression process to develop more effective therapies for mesothelioma, an aggressive form of cancer.
One promising treatment is immunotherapy that enlists the body’s natural defense system to shrink cancerous tumors. A number of immunotherapies are currently being tested in clinical trials. Mesothelioma is among the cancers that appear to be responsive to immunotherapy, researchers say. But the failure of immunotherapies to stop the growth of malignant mesothelioma tumors suggests that the immune suppression process is complex and involves multiple targets.
In an article published in the journal Immunology and Cell Biology, researchers at Harvard University investigate the roles of three factors affecting the immune response: regulatory T cells, intratumoural transforming growth factor (TGF)-â and the protein cytotoxic T lymphocyte-associated antigen-4, which plays a regulatory role in the immune system.
The researchers say that immunotherapy treatments targeting multiple regulators simultaneously appear to be more effective than focusing on one regulator protein that is suppressing immune response. They report that a triple treatment involving all three immune system factors led to long-term shrinkage of tumors and residual resistance to cancer cells if tumors reappeared.
“These data suggest that clinical application of immunotherapies against tumors may be improved by simultaneously targeting multiple mechanisms of immune suppression,” said lead investigator Haydn T. Kissick in a summary of the research.
Mesothelioma is caused by exposure to asbestos fibers. When a person breathes asbestos dust, the microscopic asbestos fibers can penetrate deep in the lungs and cause inflammation and eventually disease.
Approximately 2,500 to 3,000 people a year in the United States receive a diagnosis of malignant mesothelioma. Many victims of mesothelioma are older workers, retired workers and veterans who were exposed to asbestos decades ago in a workplace. The symptoms of mesothelioma typically take 20 years to 40 years to appear, but the disease is aggressive once it appears.
McGill Reviews Research After Questions Raised About Links to Asbestos Industry
The dean of Medicine at McGill University said in a statement Thursday that the prestigious Canadian research university will conduct a preliminary inquiry into accusations that a McGill researcher had allowed his research to be influenced by the asbestos industry. Canada remains one of the world’s leading producers of asbestos, a mineral fiber that causes serious respiratory diseases including lung cancer and mesothelioma, a cancer of the lining of the lungs and abdomen.
Dr. David Eidelman, vice principal of health affairs and dean of medicine at McGill, said a review was being undertaken to ensure that the research of Prof. J. Corbett McDonald, who is now retired, was conducted according to rigorous scientific standards. “The allegations in the media … are very serious and must be address,” Eidelman said in the statement.
A documentary last week on the CBC, Canada’s national public television and radio network, outlined how an institute established by the Quebec Asbestos Mining Association paid McGill Prof. Corbett McDonald and other researchers at least $1 million between 1966 and 1972 for research on the health effects of chrysotile asbestos. In the documentary, Professor David Eidelman of Brown University, claimed that some of the researchers altered the literature to minimize or misrepresent the health effects of chrysotile asbestos. The documentary suggested the research was still being cited by the asbestos industry and Canadian government to support Canada’s continued involvement in asbestos mining.
According to McGill University, Prof. Corbett McDonald and colleagues began in 1966 to investigate the mortality rates of approximately 11,000 Quebec miners and millers of chrysotile, a type of asbestos fiber. Asbestos exposure remains an occupational hazard for many workers. The researchers published their findings in articles in peer reviewed scientific journals from 1971 to 1998. The researchers acknowledged in the journal articles that the research was funded in part by the Institute of Occupational and Environmental Health of the Quebec Asbestos Mining Association.
In the research, McDonald demonstrated that asbestos is a carcinogen linked to lung cancer and mesothelioma. But the research also suggested that the health risks of chrysotile asbestos could be greatly minimized by reducing exposure and that chrysotile asbestos —the type of asbestos mined in Canada—was significantly safer than other types of asbestos.
Eidelman said it is true that Prof. McDonald drew different conclusions about the possible safe use of chrysotile asbestos than most scientists do today. “Holding scientific views that are different from those of the majority does not constitute research misconduct,” Eidelman said.
Eidelman said the outcome of the preliminary review conducted by a Canada Research Chair would determine whether there is a need for further investigation.
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