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Response of Mesothelioma Patients’ Tumors to Chemotherapy May Offer Clues

Thursday, July 8th, 2010

Researchers at Columbia University report that changes in the size of tumors in patients with pleural mesothelioma who have undergone chemotherapy may be useful in predicting their response to treatment and survival. Pleural Mesothelioma is an incurable cancer of the lining of the lung associated with exposure to asbestos.

Thousands of Americans have been exposed to asbestos in building materials and manufacturing, and 2,000 to 3,000 die each year of mesothelioma. Typically, 30 to 40 years elapse between the asbestos exposure and the onset of cancer symptoms. Doctors often don’t diagnose the disease until it has reached an advanced stage. The median survival is a year to 18 months.

In a new article in the Journal of Thoracic Oncology, researchers at Columbia’s Memorial Sloan-Kettering Cancer Center describe the outcomes of clinical trials involving 30 mesothelioma patients who were treated with chemotherapy followed by surgery and radiation.

The researchers took CT scans of the 30 patients’ lungs and calculated the size of their tumors before and after two rounds of chemotherapy. Patients diagnosed with stage III and stage IV cancer generally had larger tumors than those with less advanced cancer. The percentage change in the size of the tumor from the initial measurement to their evaluation after two cycles of chemotherapy was strongly associated with patients’ overall survival, the researchers said. They found a significant difference in the length of survival among patients whose tumors increased after chemotherapy and those whose tumors decreased.

The researchers said computer-aided measurements of tumors may offer doctors a more reliable way to assess patients’ response to treatment and could provide additional information about patients’ prognosis.

Labels: Mesothelioma, Research
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Researchers Report Clearer Understanding of How Asbestos Causes Mesothelioma

Tuesday, July 6th, 2010

The paradox of how asbestos kills cells and yet spurs growth of cancerous tumors has perplexed scientists for decades. A group of scientists led by researchers at the University of Hawaii claim to have new insights into the process. Their research may offer new tools to identify people at risk of developing mesothelioma and to prevent or slow tumor growth in people already diagnosed with asbestos-related disease.

Thousands of Americans have been exposed to asbestos and are at risk of developing malignant mesothelioma, a cancer of the lining of the lung or abdomen. Approximately 2,000 to 3,000 people die of mesothelioma each year in the United States and tens of thousands more worldwide. In addition, asbestos exposure raises the risks that smokers will develop lung cancer.

But the long latency period of 30 to 50 years from asbestos exposure to the appearance of tumors may offer a window of opportunity to block the trigger mechanism that causes asbestos-related cancer.

People often unknowingly inhale microscopic asbestos fibers at workplaces and the fibers can permanently lodge in the lung, causing inflammation. Most human cells exposed to asbestos die within 24 to 48 hours. Dead cells should not be able to multiply and form tumors. So how do cancerous tumors eventually form?

In an article in the Proceedings of the National Academy of Sciences, the researchers describe how asbestos kills cells through a process called programmed cell necrosis that leads to the release of a molecule called mobility group box 1 protein or HMGB1. The protein begins an inflammatory chain reaction in tissue that causes the release of mutagens that promote tumor growth. Cancer often occurs in the presence of chronic inflammation.

Asbestos exposure leads to elevated levels of HMGB1 in the blood, the researchers note. In the study, people with a history of asbestos exposure had HMGB1 levels that were more than four times higher than those of healthy people who had not been exposed.

The researchers say that mesothelial cell death and release of HMGB1 function as triggers in mechanism that leads to asbestos-related cancers. Based on that, they suggest it may be possible eventually to target HMGB1 to treat mesothelioma and identify groups of people who have been exposed to asbestos by simple blood tests to measure HMGB1 levels. By interfering with the inflammatory reaction prompted by asbestos, it may be possible to decrease the occurrence of mesothelioma and reduce the rate of tumor growth among people already diagnosed with mesothelioma.

In the future, therapeutic approaches aimed at blocking chronic inflammation and in particular the protein HMGB1 could reduce the risk of malignant mesothelioma among workers exposed to asbestos.

To test their theory, the lead researchers, Drs. Haining Yang and Michele Carbone of the University of Hawaii plan to conduct a clinical trial in Cappadocia, Turkey, where more than 50 percent of the population of two rural villages dies of mesothelioma from exposure to mineral fibers used in building materials. If the trial produces positive results, they plan to try a similar approach on groups of people exposed to asbestos in the U.S.

Labels: Cancer, Featured News, Mesothelioma, Research
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Mesothelioma Specialist Named Chief of Thoracic Surgery at Mount Sinai

Wednesday, June 9th, 2010

Renowned thoracic surgeon Raja M. Flores, M.D., who specializes in treating mesothellioma, lung cancer and esophageal cancer, has been named Chief of Thoracic Surgery at The Mount Sinai Medical Center and Director of the Thoracic Surgery Oncology Program at Mount Sinai Cancer Center, the Medical Center announced.

“Dr. Flores joins us at a propitious moment in the history of our cancer program,” Wayne Keathley, President and Chief Operating Officer of The Mount Sinai Hospital said in a press release. “We are emerging as a clear leader in caring for patients facing mesothelioma and cancers of the esophagus or lung.”

Mesothelioma is an aggressive cancer of the lining of the lung or abdomen linked to asbestos exposure. While use of asbestos has been curbed in the United States since the late 1970s, the incidence of mesothelioma has been increasing in the United States and worldwide in recent decades. The disease strikes 30 to 50 years after exposure to asbestos.

Dennis S. Charney, M.D., and Dean of Mount Sinai School of Medicine and Executive Vice President for Academic Affairs of The Mount Sinai Medical Center, said Dr. Flores had conducted a landmark study that changed the surgical treatment of pleural mesothelioma. The study, entitled “Extrapleural Pneumonectomy versus Pleurectomy Decortication in the Management of Malignant Pleural Mesothelioma,” has been one of the most frequently cited studies from the Journal of Thoracic and Cardiovascular Surgery for the last two years.

Dr. Flores helped pioneer the use of intraoperative chemotherapy for treatment of mesothelioma. The procedure involves bathing the abdominal cavity or chest cavity in a heated chemotherapy solution after removal of cancerous tumors. Heating the fluid increases the penetration of the drugs into the tissue.

Flores has co-authored more than 150 peer-reviewed manuscripts, reviews, books and book chapters and presented more than 100 lectures. His work has been published in many journals including The Journal of Clinical Oncology, Journal of Thoracic Oncology, The Annals of Surgery, The Annals of Thoracic Surgery and Vascular Surgery and other publications.

David H. Adams, M.D., chairman of the Department of Cardiothoracic Surgery at The Mount Sinai Medical Center described Dr. Flores as “a technically superb surgeon.”

“He also made efforts towards improving treatments for mesothelioma through the compilation of a database of over 1,000 patients in order to research areas of failure,” Adams said.

During the past decade, Dr. Flores has held posts at Memorial Sloan-Kettering Cancer Center, mostly recently as Associate Professor of Cardiothoracic Surgery. He is a graduate of New York University and the Albert Einstein College of Medicine, receiving his M.D. in 1992.

Dr. Flores’s appointment becomes effective Aug. 1.

Labels: Asbestos, Mesothelioma, Research, Uncategorized
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Study of Childhood Exposure to Asbestos Focuses on former Libby Residents

Thursday, June 3rd, 2010

What are the effects of exposure to low levels of asbestos on children? Are children exposed to low levels of asbestos at greater risk of developing asbestos-related diseases such as mesothelioma or autoimmune disorders later in life?

Researchers with the Mt. Sinai School of Medicine in New York in partnership with the Center for Asbestos Related Disease in Montana and the University of Montana are tackling those questions in an ambitious five-year, $4.8 million study of the effects of low level childhood exposure to asbestos. They are using as a research population people who attended high school in Libby, Montana from 1950 through 1990, then moved away and haven’t returned to live

A public health emergency has been declared in Libby because of the extent of asbestos contamination in the community related to a former vermiculite mine and the high rate of asbestos-related disease. Malignant mesothelioma, a cancer of the lining of the lung or abdomen, has occurred at a very high rate in the small northwest Montana community, federal officials say. Lung cancer rates also are 30 percent higher in the Libby population than in similar populations not exposed to asbestos, researchers say.

Through the Libby Epidemiology Research Project, the researchers hope to better understand the effects of low-level asbestos exposure on vulnerable populations such as children whose lungs aren’t fully developed and to identify protective exposure levels.

Researchers also hope to gain insight in the comparative effects of exposure to amphibole asbestos, the kind found in Libby, with chrysotile asbestos, the more common form of asbestos used in building materials and pipe insulation.

Another study will examine the correlation between autoimmune disorders such as lupus and rheumatoid arthritis with the level of Libby asbestos exposure and disease development.

The study is funded by the Agency for Toxic Substances and Disease Registry, a branch of the federal Centers for Disease Control. Dr. Stephen Levin, a nationally known expert on asbestos related disease at Mt. Sinai, is the principal investigator.

People who meet the criteria or know someone who does should contact the Center for Asbestos Related Disease at (406) 293-9274 or CARD@libbyasbestos.org

What is Meosthelioma?

Labels: Asbestos, National News, Research
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Researchers Identify Suppressor of Mesothelioma Cell Growth

Monday, May 24th, 2010

By Wade Rawlins

In the last few years, microRNAs have received lots of attention as one of the most significant scientific and medical discoveries. They appear to play a major role in reprogramming a cell to undergo uncontrolled cell division, causing growth of cancerous tumors.

An important new study published this month in The Journal of Biological Chemistry suggests the potential for using microRNAs in innovative treatment therapies to suppress tumor growth in patients with malignant mesothelioma.

Mesothelioma is a cancer associated with asbestos exposure that affects the lining of the lungs or abdomen. It is an aggressive cancer that is often resistant to chemotherapy and radiation treatments. In the United States, 2,000 to 3,000 new cases of mesothelioma are diagnosed each year.

All people —all living organisms in fact—have DNA and RNA, which are the basic building blocks of life. Each microscopic DNA molecule contains hundreds of millions of atoms in a unique sequence with the genetic information to construct cells. RNA translate the genetic information into specific instructions. MicroRNA’s are single stranded molecules that regulate gene expression. “They have been described as the body’s ‘master switches,’” according to Kenneth A. Berlin, president and CEO of Rosetta Genomics, Ltd., a developer of microRNA products used for cancer diagnostic tests.

Abnormal expression of microRNA’s has been linked to the growth of cancer, but researchers haven’t understood well the mechanics of what was occurring at a cellular level.

In the new study, medical researchers from Vanderbilt University School of Medicine, New York University Langone Medical Center and Rosetta Genomics, Ltd., analyzed cancer tissue from eight patients with advanced mesothelioma to pinpoint microRNAs linked to the progression of pleural mesothelioma,a cancer of the lining of the lung.

The researchers observed that mesothelioma cancer cells failed to express miR-31, a particular microRNA that has been linked to suppression of breast cancer tumors in mice. An assessment of miR-31 revealed its ability to inhibit the proliferation and invasion of mesothelioma cells. When researchers re-introduced miR-31 into malignant mesothelioma cells, they observed that it significantly inhibited the multiplication and formation of colonies of cancer cells.

The researchers said their analysis demonstrated that miR-31 profoundly affected cell cycle progression in malignant mesothelioma cells.

Researchers have previously connected the loss of the 9p21.3 chromosome in malignant mesothelioma cells with a rapid recurrence of tumors. In the latest research, they say the association of the loss of miR-31 with the deletion of the 9p21.3 chromosomal region and enhanced capacity of cancer cells to proliferate opens new opportunities for treatment of malignant mesothelioma and other tumors.

A study published earlier this year suggested the presence of even a single specific microRNA has significant value for predicting the course that a mesothelioma patient’s disease will take. Using microRNA as a guide, the researcher were able to accurantely divide the patients who had undergone surgery to remove tumors into two groups: those that would survive more than a year after surgery, and those that would die within 12 months. Elevated amounts of microRNA were associated with decreased spread of cancer and longer survival.

Labels: Featured News, Research
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Scientist Who Predicted Scale of Asbestos-Disease Epidemic Honored

Thursday, May 13th, 2010

Prof. Julian Peto, who has done influential research defining the environmental factors that affect development of asbestos-related cancer in the workplace, received the Medal of Honor this week from the International Agency for Research on Cancer, part of the World Health Organization.

Peto was the first researcher to predict the scale of the continuing mesothelioma epidemic. He holds a joint appointment at the Institute of Cancer Research in Great Britain and the London School of Hygiene and Tropical Medicine.

The dose response models that Peto developed for asbestos-related lung cancer and mesothelioma have been adopted internationally for assessment of occupational and environmental asbestos risk. Mesothelioma is a cancer of the lining of the lung related to asbestos exposure.

Peto began his research on asbestos in 1974 at Oxford University, under Richard Doll who was the first researcher to publish definitive evidence of the carcinogenicity of asbestos 55 years ago.

In the 1990s, Peto and colleagues predicted that asbestos-related cancer would claim a quarter of a million lives in Western Europe in the next 35 years. He predicted that one of every 150 men born from 1945 to 1950 in Western Europe would eventually die of mesothelioma, because of the prevalence of asbestos as insulation and building materials in the workplace in earlier decades.

According to the World Health Organization, about 125 million people are exposed to asbestos at work, and at least 90,000 die of asbsetos-related disease each year.

Labels: Asbestos, News, Research
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From Spinach to Butterflies, Scientist Finds Common Structure to Develop Mesothelioma Drug

Monday, May 10th, 2010

Edward C. Taylor’s name appears nowhere on the packaging of the anti-cancer medication Alimta as its inventor. But the Princeton University professor still receives thank you letters and emails from grateful mesothelioma patients who have survived well beyond their projected lifespans after starting a course of chemotherapy treatment.

Today, Alimta (known as permetrexed in injectable form) is an anti-cancer medication approved to treat malignant mesothelioma, a cancer of the lining of the lungs or abdomen associated with asbestos, and non-small cell cancers. About 85 percent to 90 percent of lung cancers are non-small cell cancer, according to the American Cancer Society.

“Even though the drug was developed and marketed by Eli Lilly, people find out that I am the inventor and send me personal notes of thanks,” Taylor told the Times of Trenton (N.J.) in a profile article. “One man from Australia, which has a lot of asbestos because it was a center of asbestos mining, was given two months to live. That was five years ago, and all traces of cancer have disappeared. He’s fit and full and vim and vigor and he wants me to know it. I have a stack of emails from him.”

The development of the drug followed decades of research and a scientific odyssey of discovery by Prof. Taylor that included fascinations with the human liver, spinach and even butterflies.

Early in his career, Taylor grew intrigued with a compound that had been identified in the human liver and that also was found in spinach leaves and was considered an essential growth factor of micro-organisms. He set out to discover the chemical connection. His scientific inquiry expanded to include butterflies after he read an article about the ring system found in the pigments in the wings of white English cabbage butterflies. As it turned out, the material from liver and spinach possessed a structure that contained as a key element, the butterfly wing pigment structure.

Scientists eventually identified the compound as folic acid, which our bodies use to make new cells and which is essential to healthy growth and development. Taylor was further intrigued that modifying the structure of folic acid slightly could change it into an anti-bacterial compound that not only stopped the growth of micro-organisms, but also caused the remission of a type of lethal leukemia. But the compound was toxic to healthy cells as well.

Taylor’s lab in the late 1970s developed a compound that functioned as an antitumor agent that was less toxic toward normal cells. Any compound that works to kill tumors and is less toxic to normal cells is of special interest to drug manufacturers. In 1985, Taylor collaborated with Eli Lilly to try to develop the compound into an anti-cancer drug. Taylor and his collaborators synthesized more than 800 potential anti-cancer compounds that didn’t work before hitting upon Alimta.

Taylor’s dogged persistence paid off. After decades of research, an estimated $2 billion in costs and 11 years of clinical trial, Alimta was approved from the Food and Drug Administration. Alimta is given in combination with cisplatin for treatment of malignant pleural mesothelioma, when surgery is not an option.

Prof. Taylor is still doing research and the royalties paid to Princeton Univesrity by Eli Lilly for Alimta are paying for construction of a new 263,000-square-foot building to house the Department of Chemistry.

Source: Times of Trenton:

http://www.nj.com/mercer/index.ssf/2010/05/his_find_became_tumors_nemesis.html

Labels: Cancer, Featured News, Research
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Researchers Observe Epidemic of Mesothelioma in Hong Kong

Monday, May 3rd, 2010

Researchers report an increasing incidence of mesothelioma from 1976 to 2000 in Hong Kong, particularly among older men and women ages 70 or older. Mesothelioma is a cancer of the lining of the lung or abdomen closely associated with asbestos exposure.

The increasing incidence in Hong Kong has culminated in an epidemic of mesothelioma since 2000 that corresponds to peak use of asbestos in the early 1960s, the researchers say in a recent article published in Environmental Health Perspectives. The average length of time from exposure to appearance of symptoms they observed was 42 years.

The researchers from the Australian National University in Canberra and the Chinese University of Hong Kong predict the number of cases of mesothelioma in Hong Kong will peak around 2014 and then slowly decline but not return to background levels. While the country has banned the use of blue and brown asbestos, Hong Kong industries continue to import and use chrysotile asbestos so the researchers say they expect new cases of mesothelioma in the future.

The trend in Hong Kong is similar to trends of asbestos-related disease in recent decades in Western European countries such as Britain, France, Germany and Italy as well as Australia and Norway.

Consumption of asbestos in Hong Kong started to increase in the 1950s in response to booming economic development in construction and shipyard industries. The country also began building massive public housing projects to accommodate the influx of hundreds of thousands of refugees from mainland China. The largest amounts of asbestos were used in 1960 to 1963, according to trade statistics.

Workplace exposure to asbestos is considered the leading risk factor associated with malignant mesothelioma. But second hand exposure also poses a risk.

The country has thousands of older buildings containing asbestos shingles and other asbestos-containing building materials that don’t meet modern fire safety codes and are candidates for urban renewal. The demolition of those buildings will unleash asbestos fibers into the environment and potentially increase the risk of mesothelioma in the community, the researchers said.

The researchers said the study provided support for an immediate worldwide ban on asbestos.

Labels: International News, Research, Uncategorized
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New Federal Study Examines Incidence of Cancers Among Firefighters

Friday, April 30th, 2010

Firefighters are exposed to smoke, soot and substances in burning buildings that are known human carcinogens such as asbestos, which was widely used in older structures. Do these repeated exposures cause a higher incidence of cancers among firefighters including asbestos-related cancers such as mesothelioma?

The U.S. Fire Administration and the National Institute for Occupational Safety and Health (NIOSH) announced this week the agencies will collaborate on a study to examine the potential increased risk of cancer among firefighters.

The broad study will analyze the health data of more than 18,000 current and retired career firefighters from suburban and large city fire departments. The study is intended to improve researchers ability to estimate risk for various cancers and to compare risk of cancer with risks for other causes of death. It also is aimed at enhancing current safety knowledge for firefighters.

As they battle fires, firefighters are exposed to soot, smoke and byproducts of combustion such as polycyclic aromatic hydrocarbons and contaminants from building products such as asbestos and formaldehyde.

By analyzing cancer cases and cancer deaths among firefighters, researchers will try to determine whether firefighters as a group develop more cancers and whether the cancers are associated with exposures to contaminants to which the firefighters may have been exposed.

“NIOSH has worked extensively with partners in the fire service to address occupational safety and health risks for firefighters,” said NIOSH Director John Howard, M.D. “We appreciate the funding and support from the U.S. Fire Administration as we engage the scientifically complex question of firefighting and cancer risk.”

NIOSH is the federal agency that conducts research and makes recommendations for preventing work-related injury, illness and death.

Labels: Asbestos, Research
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Clinical Trial of Experimental Mesothelioma Drug Promising

Thursday, April 22nd, 2010

Researchers announced positive results from tests of an experimental anti-cancer drug known as NGR-hTNF in controlling the cancer of patients with malignant pleural mesothelioma. Mesothelioma is an incurable cancer of the lining of the lung associated with asbestos exposure.

NGR-hTNF is a novel drug compound that includes a peptide—a chain of amino acids—that homes in on cancer cells—and a type of protein known as tumor necrosis factor that helps regulate the immune system response to cancerous tumors. Developed by an Italian pharmaceutical company, MolMed S.p.A., the drug is designed to better permeate cancerous tumors and act directly on blood vessels that feed a tumor’s growth.

In an article published this week in the Journal of Clinical Oncology, Italian researchers said NGR-hTNF was given to 57 mesothelioma patients either every three weeks or every week. The patients had previously undergone chemotherapy and had a relapse. The results showed the drug temporarily stopped the advance of the cancer in 26 patients for about five months on average. Median survival was 12 months.

The researchers said the disease control provided by NGR-hTNF and patients’ ability to tolerate the drug warranted further study with patients with advanced pleural mesothelioma.

The drug is being studied as an alternative treatment for patients whose cancer is not responding to the more standard chemotherapy regimen involving permetrexed. A phase III clinical study is underway. Researchers are exploring it use by itself or in combination with other medications.

On the basis of the latest results, the drug was granted orphan drug designation for treatment of malignant mesothelioma in the United State and in Europe, MolMed S.p.A., announced.

The federal Orphan Drug Act provides special status to drugs used to treat a rare disease or condition at the request of the drug sponsor. MolMed S.p.A., an Italian pharmaceutical company, is developing the drug. The orphan designation provides tax credits and government incentives to sponsors that bring develop drugs to treat rare diseases. About 2,000 to 3,000 people die of mesothelioma in the United States each year, but incidence of the disease has increased significantly in recent decades.

The drug must go through the Food and Drug Administration marketing approval process like any other drug. Orphan drugs often receive expedited review because they are for serious or life threatening diseases, according to the Food and Drug Administration.

Labels: Mesothelioma, Research
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Contributing Author

Wade Rawlins is a former environmental reporter with the Raleigh News & Observer.

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