Category: Research
Researchers Report Clearer Understanding of How Asbestos Causes Mesothelioma
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.
Researchers Identify Suppressor of Mesothelioma Cell Growth
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 researchers were able to accurately 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.
Researchers Observe Epidemic of Mesothelioma in Hong Kong
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.
New York 9/11 Firefighters Have Abnormal Lung Function Years Later
By Wade Rawlins
New York Firefighters and rescue workers who inhaled the noxious cloud of dust, chemicals and asbestos debris at Ground Zero after the 9/11 terrorist attacks still have significantly abnormal lung function years later, a new medical study says.
In a study published in The New England Journal of Medicine, researchers with the Albert Einstein College of Medicine, the New York University School of Medicine and the New York Fire Department said they had observed little or no recovery of lung function among firefighters in the nearly decade since they responded to the attacks on the World Trade Center.
The medical researchers compared before and after 9/11 lung function tests of more than 12,700 active and retired New York Fire Department firefighters and rescue personnel — more than 90 percent of those who responded. Their aim is to understand the longer term health effects of the massive exposure to dust and debris at the World Trade Center site based on repeated follow-up lung testing.
The massive exposure to dust at the World Trade Center on 9/11 and repeated exposure to lesser amounts over the subsequent recovery operations led to significant declines in respiratory function in the first year after 9/11 among both firefighters and EMS workers with no history of smoking, the researchers say.
Firefighters had the heaviest exposure to dust and experienced the largest decline in lung function in the first year after 9/11, researchers said. It was more than 12 times the average rate of loss of lung function adjusted for age. Surprisingly, the FDNY firefighters recovered little or none of lung function as shown by follow up tests in a six year period September 2008, the researchers said.
Of those tested, about 13 percent of firefighters and 22 percent of EMS workers who never smoked still had abnormal lung function seven years after 9/11, the study said. Before 9/11, few firefighters had abnormal lung function tests.
Typically, firefighters show no long lasting respiratory effects of smoke inhalation, the researchers said. In the absence of overwhelming exposure, smoke inhalation during firefighting usually causes mild and reversible respiratory impairment.
The researchers said they could not analyze the effect of the use of masks and respirators on lung function, because the use of such safety equipment was minimal during the first weeks after 9/11
Declines in respiratory function also occurred and persisted among non-FDNY rescue workers and volunteers at Ground Zero. other volunteers and workers. But health records were not available among this group to compare lung function before 9/11 to afterward.
Some dust from the World Trade Center collapse contained asbestos and other contaminants, according to the U.S. Environmental Protection Agency. But the agency said at the time that the majority of air and dust sample monitored at the site did not indicate levels of public concern. Inhaling airborne asbestos is closely associated with respiratory disease including lung cancer and mesothelioma, a cancer of the lining of the lung. Mesothelioma has a long latency period and typically takes 20 to 40 years after exposure for symptoms to appear.
Increased Asbestos Use in Mexico Leading to More Mesothelioma Deaths
Industrial uses of asbestos in Mexico are increasing the number of mesothelioma-related diseases and deaths among Mexican workers, according to a scientific study in the American Journal of Industrial Medicine. The researchers say Mexico should ban the use of asbestos in all production processes as a public health policy to control the epidemic of asbestos-related diseases and safeguard the population and future generations.
Malignant mesothelioma is an incurable cancer of the lining of the lungs or abdomen closely associated with breathing asbestos. The World Health Organization has urged countries to ban the use of asbestos, saying there is no safe level of asbestos exposure.
In their study, occupational health researchers from the Mexican Institute of Social Security and several Mexican cancer hospitals sought to identify the proportion of cases of malignant pleural mesothelioma in Mexico that were attributable to workplace exposure. Despite numerous studies around the world that have underscored the adverse effects of asbestos on workers’ health, the researchers said there was a general lack of recognition of the hazard of asbestos exposure in Mexico.
Because mesothelioma is not recognized as a work-related disease in Mexico, the country’s national health system and Mexican Institute of Social Security, which insures 30 percent of the country’s economically active population, absorb millions of dollars in costs to care for patients with mesothelioma rather than the industries that caused their disease.
In Mexico, chrysotile asbestos —also known as white asbestos—imported from Canada is the most commonly used asbestos fiber and represents the largest threat to workers, the study says. The shipment of asbestos to Mexico is part of an ongoing migration of dangerous industries to less industrialized countries such as Mexico that possess a weak framework for worker protection, the researchers noted. From 1991-2000, Mexico imported about 8 percent of Canada’s total international exports of asbestos, representing $114 million in exports.
Researchers interviewed 472 workers who lived in the Valley of Mexico, an area of central Mexico that encompasses the Mexico City metropolitan area, to assess their potential exposure to asbestos from their jobs as well as from environmental factors such as living near an asbestos factory or having parents who worked around asbestos. More than 100 of the workers had been diagnosed with mesothelioma.
The researchers attributed 82 percent of the cases of mesothelioma in the lining of the lung to workplace exposure to asbestos. They said the pattern of asbestos exposure and disease observed in more industrialized nations in the 1970s is now repeating itselt in Mexico.
“Our results show a clear relationship between industrial use of all types of asbestos and malignant pleural mesothelioma, and in Mexico the major type of asbestos is chrysotile imported from Canada,” the researchers said.
They said deaths from mesothelioma appeared to be underreported in Mexico’s official death records, suggesting the scope of the problem was even greater. Of more than 100 patients diagnosed with mesothelioma, only about a third of patients who had died had mesothelioma listed as a cause of death.
In 2006, the World Health Organization said that all types of asbestos cause mesothelioma, lung cancer and asbestosis and there is no safe level of exposure to asbestos. Even if use of asbestos is eliminated soon, the World Health Organization has estimated there will be 5 to 10 million additional deaths from asbestos. The World Health Organization called for a ban.
But Mexico has not banned asbestos. To the contrary, Mexico’s government supported an effort by asbestos-exporting countries, led by Canada, to block the United Nations from including chrysotile asbestos on a list of recognized toxic substances.
Based of their findings, the researchers called on Mexico to ban the use and commercialization of all forms of asbestos to protect future generations and to require asbestos manufacturers and importers to pay the medical expenses and pensions of diseased workers. The researchers said if asbestos is not banned at once in Mexico, the incidence of mesothelioma would continue to increase in the population for 50 years.
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