They report these findings in the May 2009 issue of The American Journal of Pathology.
TIP30 is a putative tumor suppressor with decreased expression in numerous cancers including melanoma, breast cancer, and colon cancer. Lung cancer is the most common cancer worldwide, both in terms of incidence and of mortality.
To determine if TIP30 plays a role in lung cancer progression and metastasis, Tong et al examined TIP30 expression in paired cancerous and non-cancerous lung tissue. TIP30 expression was decreased in a third of non-small cell lung cancers compared with normal controls, and reduced TIP30 expression correlated with lymph node metastasis. In addition, inhibition of TIP30 expression promoted lung cancer metastasis and angiogenesis in mice,
Tong et al conclude that "TIP30 may function as a tumor suppressor gene and play important roles in suppressing the progression and metastasis of lung cancer." These findings highlight TIP30 as a potential new therapeutic for metastatic lung cancer.
Saturday, August 1, 2009
One Of The Mechanisms That Prevents Spread Of Colon Cancer Discovered
Researchers at IRB Barcelona under the direction of Eduard Batlle, ICREA researcher and head of IRB Barcelona's Oncology Programme, have discovered a new mechanism by which the benign tumour cells receive instructions to grow in confined compartments, and no to invade other areas of the tissue. The description of this new tumour suppression mechanism is reported in the scientific journal Nature Genetics.
The scientists observed that adenomatous tumour cells have special surface receptors, called EphB2 and EphB3, which detect the presence of certain ligands in the healthy tissue that surround them. These receptors and their ligands serve to organize the structure of intestinal tissue. Thanks to the activity of EphB2 and EphB3, the tumour cells are forced to "listen to" the signals that they receive from their environment.
These signals make the benign tumours grow in a confined space, from which they are unable to spread. "We knew that these receptors worked as tumour suppressors, but we did not know how. Now we have been able to observe that they compartmentalize the tumour, thereby preventing its spread", explains Batlle.
Until the tumour cells learn to deactivate these receptors, they cannot invade other tissue outside the compartment. Batlle goes on to say, "as the tumour cells progress to become malignant, their genetic programme is refined and they remove the signals that block their growth, including these two receptors, which impose positional information".
This study explains one of the key mechanisms of how a benign tumour transforms into a malignant one during the onset of colon cancer. Using experiments performed with animal models and in vitro cells, the scientists determined that the loss of compartmentalization, that is to say, the loss-of-function of these two receptors, is one of the vital factors in the development of adenoma-derived colon cancer.
It is estimated that between 30 and 50% of people over 60 years of age may develop one of these benign adenomas. Cancer of the colon ranks first in the list of the most common cancers in Spain, with more than 25,000 causes diagnosed each year. Last year alone, more than half a million people worldwide died as a result of this disease.
The scientists observed that adenomatous tumour cells have special surface receptors, called EphB2 and EphB3, which detect the presence of certain ligands in the healthy tissue that surround them. These receptors and their ligands serve to organize the structure of intestinal tissue. Thanks to the activity of EphB2 and EphB3, the tumour cells are forced to "listen to" the signals that they receive from their environment.
These signals make the benign tumours grow in a confined space, from which they are unable to spread. "We knew that these receptors worked as tumour suppressors, but we did not know how. Now we have been able to observe that they compartmentalize the tumour, thereby preventing its spread", explains Batlle.
Until the tumour cells learn to deactivate these receptors, they cannot invade other tissue outside the compartment. Batlle goes on to say, "as the tumour cells progress to become malignant, their genetic programme is refined and they remove the signals that block their growth, including these two receptors, which impose positional information".
This study explains one of the key mechanisms of how a benign tumour transforms into a malignant one during the onset of colon cancer. Using experiments performed with animal models and in vitro cells, the scientists determined that the loss of compartmentalization, that is to say, the loss-of-function of these two receptors, is one of the vital factors in the development of adenoma-derived colon cancer.
It is estimated that between 30 and 50% of people over 60 years of age may develop one of these benign adenomas. Cancer of the colon ranks first in the list of the most common cancers in Spain, with more than 25,000 causes diagnosed each year. Last year alone, more than half a million people worldwide died as a result of this disease.
Inflammatory Biomarker Helps Identify Progressive Precancerous Lesions In The Lung
The results appear in the first issue for March 2005 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.
Stephen Lam, M.D., F.R.C.P.C., of the Lung Tumour Group, British Columbia Cancer Agency at the University of British Columbia in Vancouver, Canada, and three associates measured CRP, lung function and other inflammatory markers in 65 individuals. All participants had at least one abnormal cell site in their lungs (bronchial dysplasia) greater than 1.2 millimeters in size, which was biopsied at the start of the study and re-examined 6 months later.
Of the study cohort, 49 individuals (75 percent) were men, with 48 classified as current smokers. On average, study participants were 57 years old and had 52 pack-years of smoking history.
"Lung cancer is a worldwide epidemic," said Dr. Lam. "More than 300 million people die of this disease annually. In the United States alone, 170,000 new cases of lung cancer are reported each year. Most of these are non-small cell lung cancer and the overall prognosis once diagnosed is dismal. The only reasonable chance of cure is surgical resection for early stage tumors. However, most patients with early lung cancer are asymptomatic. Symptoms usually develop after the tumors become invasive or disseminated and curative resection is infeasible."
Consequently, researchers have been working to find novel non-invasive or semi-invasive methods of identifying individuals who harbor progressive precancerous lesions. If detected early, these lesions might be treated with a chemopreventive agent to impede progress to invasive carcinoma.
In the study, the level of CRP only differed between individuals who either did or did not develop progression in their bronchial lesions.
"The odds of developing progressive disease were 9.6 fold higher in the group that had CRP greater than 0.5 mg per liter compared with the group less than this threshold," said Dr. Lam.
There were 32 subjects whose bronchial lesions had progressed to a more abnormal state when biopsied after 6 months.
"These data are consistent with the prevailing hypothesis that squamous cell carcinoma arises from preinvasive lesions in stepwise fashion, which is called the sequential theory of cancer development," said Dr. Lam. "This hypothesis is supported by animal experiments mimicking human carcinogenesis."
The authors believe that these results will be helpful in designing future chemopreventive and early detection studies by identifying high-risk subjects for non-small cell lung cancer.
Stephen Lam, M.D., F.R.C.P.C., of the Lung Tumour Group, British Columbia Cancer Agency at the University of British Columbia in Vancouver, Canada, and three associates measured CRP, lung function and other inflammatory markers in 65 individuals. All participants had at least one abnormal cell site in their lungs (bronchial dysplasia) greater than 1.2 millimeters in size, which was biopsied at the start of the study and re-examined 6 months later.
Of the study cohort, 49 individuals (75 percent) were men, with 48 classified as current smokers. On average, study participants were 57 years old and had 52 pack-years of smoking history.
"Lung cancer is a worldwide epidemic," said Dr. Lam. "More than 300 million people die of this disease annually. In the United States alone, 170,000 new cases of lung cancer are reported each year. Most of these are non-small cell lung cancer and the overall prognosis once diagnosed is dismal. The only reasonable chance of cure is surgical resection for early stage tumors. However, most patients with early lung cancer are asymptomatic. Symptoms usually develop after the tumors become invasive or disseminated and curative resection is infeasible."
Consequently, researchers have been working to find novel non-invasive or semi-invasive methods of identifying individuals who harbor progressive precancerous lesions. If detected early, these lesions might be treated with a chemopreventive agent to impede progress to invasive carcinoma.
In the study, the level of CRP only differed between individuals who either did or did not develop progression in their bronchial lesions.
"The odds of developing progressive disease were 9.6 fold higher in the group that had CRP greater than 0.5 mg per liter compared with the group less than this threshold," said Dr. Lam.
There were 32 subjects whose bronchial lesions had progressed to a more abnormal state when biopsied after 6 months.
"These data are consistent with the prevailing hypothesis that squamous cell carcinoma arises from preinvasive lesions in stepwise fashion, which is called the sequential theory of cancer development," said Dr. Lam. "This hypothesis is supported by animal experiments mimicking human carcinogenesis."
The authors believe that these results will be helpful in designing future chemopreventive and early detection studies by identifying high-risk subjects for non-small cell lung cancer.
Chest Scans May Help Monitor Spread Of Head And Neck Cancer In High-risk Patients
Developing a second, distant cancer (a metastasis or a new primary cancer) is an important factor affecting survival of patients with head and neck squamous cell carcinoma, which accounts for most head and neck cancers, according to background information in the article. The most common site at which such patients develop new metastases is the lungs, with an incidence of 8 percent to 15 percent. Chest X-rays are the most commonly used screening tool for detecting these malignancies but do not always identify early abnormalities.
Yen-Bin Hsu, M.D., of Taipei Veterans General Hospital, Taiwan, and colleagues evaluated 270 screening chest CT scans performed over 42 months in 192 patients with head and neck squamous cell carcinoma. The scans were categorized as new cases, follow-up cases or recurrent cases, and results classified as normal or abnormal.
Of the 270 scans, 79 (29.3 percent) were considered abnormal, including 54 (20 percent) that identified a malignant neoplasm of the lung and 25 (9.3 percent) showing indeterminate abnormalities. "The rate of an abnormal scan was significantly higher in the follow-up case group (44.2 percent) than in the new case group (14.2 percent)," the authors write. Patients whose cancer was classified as stage N2 or N3 (indicating some degree of lymph node involvement), who had stage IV disease (in which the cancer has spread to another organ), who had recurrent disease or who had a distant metastasis in another site were more likely to have a malignant neoplasm of the lung.
"Indeterminate lesions were common on chest CT in our study, and special attention should be paid to them," the authors write. "Based on the progressive changes in follow-up scans, 44 percent of indeterminate lesions were eventually considered a malignant neoplasm of the lung. We also found that small (less than 1 centimeter) solitary nodules, which were usually resectable [operable], carried significantly higher chances (66.7 percent) of being a malignant neoplasm."
"For patients with head and neck squamous cell carcinoma, chest diagnosis is crucial and may influence their treatment plan," they continue. "In conclusion, chest CT is recommended for high-risk patients, especially every six months for the first two years during the follow-up period, although its role is controversial for patients newly diagnosed as having head and neck squamous cell carcinoma. High-risk patients include those with N2 or N3 disease, stage IV disease or locoregional recurrence. For patients with indeterminate small (less than 1 centimeter) solitary pulmonary nodules, aggressive evaluation and management are imperative because of the high rate of a malignant neoplasm of the lung."
Yen-Bin Hsu, M.D., of Taipei Veterans General Hospital, Taiwan, and colleagues evaluated 270 screening chest CT scans performed over 42 months in 192 patients with head and neck squamous cell carcinoma. The scans were categorized as new cases, follow-up cases or recurrent cases, and results classified as normal or abnormal.
Of the 270 scans, 79 (29.3 percent) were considered abnormal, including 54 (20 percent) that identified a malignant neoplasm of the lung and 25 (9.3 percent) showing indeterminate abnormalities. "The rate of an abnormal scan was significantly higher in the follow-up case group (44.2 percent) than in the new case group (14.2 percent)," the authors write. Patients whose cancer was classified as stage N2 or N3 (indicating some degree of lymph node involvement), who had stage IV disease (in which the cancer has spread to another organ), who had recurrent disease or who had a distant metastasis in another site were more likely to have a malignant neoplasm of the lung.
"Indeterminate lesions were common on chest CT in our study, and special attention should be paid to them," the authors write. "Based on the progressive changes in follow-up scans, 44 percent of indeterminate lesions were eventually considered a malignant neoplasm of the lung. We also found that small (less than 1 centimeter) solitary nodules, which were usually resectable [operable], carried significantly higher chances (66.7 percent) of being a malignant neoplasm."
"For patients with head and neck squamous cell carcinoma, chest diagnosis is crucial and may influence their treatment plan," they continue. "In conclusion, chest CT is recommended for high-risk patients, especially every six months for the first two years during the follow-up period, although its role is controversial for patients newly diagnosed as having head and neck squamous cell carcinoma. High-risk patients include those with N2 or N3 disease, stage IV disease or locoregional recurrence. For patients with indeterminate small (less than 1 centimeter) solitary pulmonary nodules, aggressive evaluation and management are imperative because of the high rate of a malignant neoplasm of the lung."
Early Detection Of Lung Cancer
Lung cancer is the leading cause of cancer deaths worldwide and also in Europe. One of the reasons for this is that symptoms of lung cancer are very often lacking or occur only late in the course of the disease," said Prof Rudolf M. Huber from the University of Munich in Germany.
"The prognosis of lung cancer patients is very dependent on how advanced their disease is. In stage I for example, where the tumour has not yet spread, 5-year-survival rates are about 70%; whereas in stage IV, where it has metastasised to other parts of the body, survival is about 1%. Even for patients with locally advanced tumours, survival over 5 years is only about 10%. Therefore every effort should be undertaken to diagnose early in the course of the disease."
"Developing better tools for distinguishing between lung cancer and other lung diseases will help us offer greater hope for patients," added Prof Huber.
In one study presented at the conference, Italian researchers compare two computed tomography techniques for diagnosing indeterminate lung lesions, finding that a form of single-photon emission computed tomography could offer an alternative method in situations where positron emission tomography is not available.
In another abstract, UK scientists report that a new approach to diagnosis that ensures a patient has had a chest CT scan before they attend a clinic has the potential to reduce the time between their first abnormal chest X-ray and final diagnosis.
Also during the conference, Greek investigators suggest that they may have found a new factor that will help indicate a patient's prognosis at the time of diagnosis. Their work indicates that the expression of specific cell surface molecules on tumour cells correlates with clinical parameters. The results "could comprise a promising prognostic factor in lung carcinomas, thus presenting exciting possibilities for the future."
"The prognosis of lung cancer patients is very dependent on how advanced their disease is. In stage I for example, where the tumour has not yet spread, 5-year-survival rates are about 70%; whereas in stage IV, where it has metastasised to other parts of the body, survival is about 1%. Even for patients with locally advanced tumours, survival over 5 years is only about 10%. Therefore every effort should be undertaken to diagnose early in the course of the disease."
"Developing better tools for distinguishing between lung cancer and other lung diseases will help us offer greater hope for patients," added Prof Huber.
In one study presented at the conference, Italian researchers compare two computed tomography techniques for diagnosing indeterminate lung lesions, finding that a form of single-photon emission computed tomography could offer an alternative method in situations where positron emission tomography is not available.
In another abstract, UK scientists report that a new approach to diagnosis that ensures a patient has had a chest CT scan before they attend a clinic has the potential to reduce the time between their first abnormal chest X-ray and final diagnosis.
Also during the conference, Greek investigators suggest that they may have found a new factor that will help indicate a patient's prognosis at the time of diagnosis. Their work indicates that the expression of specific cell surface molecules on tumour cells correlates with clinical parameters. The results "could comprise a promising prognostic factor in lung carcinomas, thus presenting exciting possibilities for the future."
Carbon Nanotubes That Look Like Asbestos, Behave Like Asbestos, Could Lead To Asbestos-related Disease
A major study published in Nature Nanotechnology suggests some forms of carbon nanotubes -- a poster child for the "nanotechnology revolution" -- could be as harmful as asbestos if inhaled in sufficient quantities.
The study used established methods to see if specific types of nanotubes have the potential to cause mesothelioma -- a cancer of the lung lining that can take 30-40 years to appear following exposure. The results show that long, thin multi-walled carbon nanotubes that look like asbestos fibers, behave like asbestos fibers.
Discovered nearly 20 years ago, carbon nanotubes have been described as the wonder material of the 21st Century. Light as plastic and stronger that steel, they are being developed for use in new drugs, energy-efficient batteries and futuristic electronics. But since their discovery, questions have been raised about whether some of these nanoscale materials may cause harm and undermine a nascent market for all types of carbon nanotubes, including multi- and single-walled carbon nanotubes. Leading forecasting firms say sales of all nanotubes could reach $2 billion annually within the next four to seven years, according to an article in the U.S. publication Chemical & Engineering News.
"This study is exactly the kind of strategic, highly focused research needed to ensure the safe and responsible development of nanotechnology," says Andrew Maynard, Chief Science Advisor to the Project on Emerging Nanotechnologies and a co-author on the paper. "It looks at a specific nanoscale material expected to have widespread commercial applications and asks specific questions about a specific health hazard. Even though scientists have been raising concerns about the safety of long, thin carbon nanotubes for over a decade, none of the research needs in the current U.S. federal nanotechnology environment, health and safety risk research strategy address this question."
Widespread exposure to asbestos has been described as the worst occupational health disaster in U.S. history and the cost of asbestos-related disease is expected to exceed $200 billion, according to major U.S. think tank RAND Corporation.
Anthony Seaton, MD, a co-author on the paper and a professor emeritus at the University of Aberdeen in the United Kingdom, says, "The toll of asbestos-related cancer, first noticed in the 1950s and 1960s, is likely to continue for several more decades even though usage reduced rapidly some 25 years ago. While there are reasons to suppose that nanotubes can be used safely, this will depend on appropriate steps being taken to prevent them from being inhaled in the places they are manufactured, used and ultimately disposed of. Such steps should be based on research into exposure and risk prevention, leading to regulation of their use. Following this study, the results of which were foreseen by the Royal Society in the U.K. in 2004, we can no longer delay investing in such research."
Researchers, led by Professor Kenneth Donaldson at the University of Edinburgh in the United Kingdom, examined the potential for long and short carbon nanotubes, long and short asbestos fibers, and carbon black to cause pathological responses known to be precursors of mesothelioma. Material was injected into the abdominal cavity of mice -- a sensitive predictor of long fiber response in the lung lining.
"The results were clear," says Donaldson. "Long, thin carbon nanotubes showed the same effects as long, thin asbestos fibers."
Asbestos fibers are harmful because they are thin enough to penetrate deep into the lungs, but sufficiently long to confound the lungs' built-in clearance mechanisms for getting rid of particles.
Donaldson stresses there are still pieces of the puzzle to fill in. "We still don't know whether carbon nanotubes will become airborne and be inhaled, or whether, if they do reach the lungs, they can work their way to the sensitive outer lining. But if they do get there in sufficient quantity, there is a chance that some people will develop cancer--perhaps decades after breathing the stuff," states Donaldson.
There is a silver lining to this research. According to Donaldson, "Short or curly carbon nanotubes did not behave like asbestos, and by knowing the possible dangers of long, thin carbon nanotubes, we can work to control them. It's a good news story, not a bad one. It shows that carbon nanotubes and their products could be made to be safe."
But Donaldson added that the present study only tested for fiber-like behavior and did not exonerate carbon nanotubes from damaging the lungs in other ways. "More research is still needed if we are to understand how to use these materials as safely as possible," he notes.
Carbon nanotubes are atom-thick sheets of graphite formed into cylinders. They may be formed from a single layer of graphite or they may consist of multiple concentric layers of graphite, resulting in multi-walled carbon nanotubes. While the diameter of a nanotube can vary from a few nanometers up to tens of nanometers, they can be hundreds or even thousands of nanometers long. Carbon nanotubes come in many forms, with different shapes, different atomic arrangements, and varying amounts and types of added chemicals--all of which affect their properties and might influence their impact on human health and the environment.
"This is a wakeup call for nanotechnology in general and carbon nanotubes in particular," says Maynard. "As a society, we cannot afford not to exploit this incredible material, but neither can we afford to get it wrong--as we did with asbestos."
The study used established methods to see if specific types of nanotubes have the potential to cause mesothelioma -- a cancer of the lung lining that can take 30-40 years to appear following exposure. The results show that long, thin multi-walled carbon nanotubes that look like asbestos fibers, behave like asbestos fibers.
Discovered nearly 20 years ago, carbon nanotubes have been described as the wonder material of the 21st Century. Light as plastic and stronger that steel, they are being developed for use in new drugs, energy-efficient batteries and futuristic electronics. But since their discovery, questions have been raised about whether some of these nanoscale materials may cause harm and undermine a nascent market for all types of carbon nanotubes, including multi- and single-walled carbon nanotubes. Leading forecasting firms say sales of all nanotubes could reach $2 billion annually within the next four to seven years, according to an article in the U.S. publication Chemical & Engineering News.
"This study is exactly the kind of strategic, highly focused research needed to ensure the safe and responsible development of nanotechnology," says Andrew Maynard, Chief Science Advisor to the Project on Emerging Nanotechnologies and a co-author on the paper. "It looks at a specific nanoscale material expected to have widespread commercial applications and asks specific questions about a specific health hazard. Even though scientists have been raising concerns about the safety of long, thin carbon nanotubes for over a decade, none of the research needs in the current U.S. federal nanotechnology environment, health and safety risk research strategy address this question."
Widespread exposure to asbestos has been described as the worst occupational health disaster in U.S. history and the cost of asbestos-related disease is expected to exceed $200 billion, according to major U.S. think tank RAND Corporation.
Anthony Seaton, MD, a co-author on the paper and a professor emeritus at the University of Aberdeen in the United Kingdom, says, "The toll of asbestos-related cancer, first noticed in the 1950s and 1960s, is likely to continue for several more decades even though usage reduced rapidly some 25 years ago. While there are reasons to suppose that nanotubes can be used safely, this will depend on appropriate steps being taken to prevent them from being inhaled in the places they are manufactured, used and ultimately disposed of. Such steps should be based on research into exposure and risk prevention, leading to regulation of their use. Following this study, the results of which were foreseen by the Royal Society in the U.K. in 2004, we can no longer delay investing in such research."
Researchers, led by Professor Kenneth Donaldson at the University of Edinburgh in the United Kingdom, examined the potential for long and short carbon nanotubes, long and short asbestos fibers, and carbon black to cause pathological responses known to be precursors of mesothelioma. Material was injected into the abdominal cavity of mice -- a sensitive predictor of long fiber response in the lung lining.
"The results were clear," says Donaldson. "Long, thin carbon nanotubes showed the same effects as long, thin asbestos fibers."
Asbestos fibers are harmful because they are thin enough to penetrate deep into the lungs, but sufficiently long to confound the lungs' built-in clearance mechanisms for getting rid of particles.
Donaldson stresses there are still pieces of the puzzle to fill in. "We still don't know whether carbon nanotubes will become airborne and be inhaled, or whether, if they do reach the lungs, they can work their way to the sensitive outer lining. But if they do get there in sufficient quantity, there is a chance that some people will develop cancer--perhaps decades after breathing the stuff," states Donaldson.
There is a silver lining to this research. According to Donaldson, "Short or curly carbon nanotubes did not behave like asbestos, and by knowing the possible dangers of long, thin carbon nanotubes, we can work to control them. It's a good news story, not a bad one. It shows that carbon nanotubes and their products could be made to be safe."
But Donaldson added that the present study only tested for fiber-like behavior and did not exonerate carbon nanotubes from damaging the lungs in other ways. "More research is still needed if we are to understand how to use these materials as safely as possible," he notes.
Carbon nanotubes are atom-thick sheets of graphite formed into cylinders. They may be formed from a single layer of graphite or they may consist of multiple concentric layers of graphite, resulting in multi-walled carbon nanotubes. While the diameter of a nanotube can vary from a few nanometers up to tens of nanometers, they can be hundreds or even thousands of nanometers long. Carbon nanotubes come in many forms, with different shapes, different atomic arrangements, and varying amounts and types of added chemicals--all of which affect their properties and might influence their impact on human health and the environment.
"This is a wakeup call for nanotechnology in general and carbon nanotubes in particular," says Maynard. "As a society, we cannot afford not to exploit this incredible material, but neither can we afford to get it wrong--as we did with asbestos."
Naturally Occurring Asbestos Linked To Lung Cancer
The study - the largest to examine the question - will be published this fall in the American Journal of Respiratory and Critical Care Medicine.
Exposure to asbestos in the workplace, particularly in shipyards, has long been recognized as a risk factor for mesothelioma, a rare form of cancer affecting the lining of the lung. But in the new study, researchers found a consistent and dose-dependent association between mesothelioma and residential proximity to ultramafic rock, the predominant source of naturally occurring asbestos.
"Our findings indicate that the risks from exposure to naturally occurring asbestos, while low, are real and should be taken seriously," said Marc Schenker, professor and chair of the UC Davis Department of Public Health Sciences and the study's senior author. "This study provides important supportive evidence that naturally occurring asbestos causes mesothelioma - and public efforts should now shift to understanding the risk and how we can protect people from this preventable malignancy."
To put the mesothelioma risk in perspective, the disease kills about the same number of Americans each year as passive smoking. About 2,500 people a year die from mesothelioma in the United States, according to National Institute of Occupational Safety and Health statistics. About 3,000 deaths a year are attributed to exposure to secondhand tobacco smoke, according to U.S. Environmental Protection Agency statistics.
Ultramafic rock is distributed throughout the Sierra Nevada, Coast Ranges and Klamath Mountains in Northern and Central California, and has been a source of increasing concern as new housing developments cut through these areas. Of most concern are the areas of ultramafic rock associated with tremolite asbestos.
In their ambitious study, Schenker and his colleagues used California Cancer Registry data to identify 2,908 cases of malignant mesothelioma diagnosed between 1988 and 1997 in adults ages 35 and older. In most cases, the registry also provided occupational history. As a control group, an equal number of age- and gender-matched pancreatic cancer cases was selected (since pancreatic cancer has no known association to asbestos exposure). For both the mesothelioma and pancreatic cancer cases, the researchers employed sophisticated geographic information system mapping to pinpoint home or street addresses for every diagnosed individual. A map from the California Department of Conservation, Division of Mines and Geology, served as the reference for ultramafic rock deposits. Finally, statistical adjustments were made for sex, occupational asbestos exposure and age at diagnosis.
The researchers found that the risk of developing malignant mesothelioma was directly related to residential proximity to a source of ultramafic rock. Specifically, the odds of having mesothelioma fell by 6.3 percent for every 10 kilometers (about 6.2 miles) farther a person lived from the nearest asbestos source. The association was strongest in men, but was also seen in women. No such association showed up in the pancreatic cancer group. The study was not designed to determine the "ground zero" risk for those living closest to an asbestos source - only to test for a relationship between proximity and risk.
"This is very creative, painstaking epidemiology," said Jerrold L. Abraham, professor and director of environmental and occupational pathology at SUNY Upstate Medical University in Syracuse, New York, and a leading authority on mesothelioma. "The UC Davis researchers have shown a significant association between living near deposits of naturally occurring asbestos and mesothelioma. This is the strongest evidence possible without conducting one-on-one interviews with each diagnosed mesothelioma patient or his or her family."
Laurel Beckett, professor and vice chair of the UC Davis Department of Public Health Sciences and a study co-author, said the findings are important. "We showed that breathing asbestos in your community is not magically different from breathing asbestos in an industrial setting. It would have been a surprise to find otherwise."
Similarly, she said, it was no real surprise to scientists when passive smoking was found to cause lung cancer. "Like smoking, exposure to asbestos appears to be very dose-dependent," Beckett said. "Day-in, day-out occupational exposures are more dangerous than intermittent exposures in the community. But the more you can do to reduce your personal exposure, the safer you will be."
While the overall mesothelioma rate was about one case per 100,000 people per year in the California study, the rate varied markedly by gender and age. For white males, the rate was 2.29 cases per 100,000. For white females, it was 0.49. People over age 60 had ten times the rate of those ages 40 to 59.
Worldwide, epidemiological studies of mesothelioma have found occupational causes for most but not all cases of the disease. In some undeveloped areas of the world, including parts of Greece and Turkey, mesothelioma cases have been linked to use of naturally occurring asbestos in household materials such as whitewash. The UC Davis study suggests naturally occurring asbestos also causes mesothelioma in developed countries, through incidental, non-occupational exposures.
California has required statewide cancer reporting since 1985 and established the California Cancer Registry in 1988. One of the largest cancer databases in the world, the registry is responsible for collecting cancer incidence and mortality statistics for more than one tenth of the United States population. An estimated 98.9 percent of all mesothelioma cases diagnosed in California are reported to the registry.
The registry's size enabled researchers to identify an association that might not have been apparent in a smaller study.
Needed now are field studies to more accurately characterize determinants of exposure to asbestos fibers among residents in areas with naturally occurring asbestos, Schenker said. In addition, he said more must be learned about the types and size of fibers in asbestos deposits, the types of human activities that disturb asbestos fibers and the determinants of cancer risk in exposed populations.
"Because mesothelioma takes 20 to 30 years to develop, what we learn today will allow us to protect Californians from this preventable cancer decades into the future," Schenker said.
Exposure to asbestos in the workplace, particularly in shipyards, has long been recognized as a risk factor for mesothelioma, a rare form of cancer affecting the lining of the lung. But in the new study, researchers found a consistent and dose-dependent association between mesothelioma and residential proximity to ultramafic rock, the predominant source of naturally occurring asbestos.
"Our findings indicate that the risks from exposure to naturally occurring asbestos, while low, are real and should be taken seriously," said Marc Schenker, professor and chair of the UC Davis Department of Public Health Sciences and the study's senior author. "This study provides important supportive evidence that naturally occurring asbestos causes mesothelioma - and public efforts should now shift to understanding the risk and how we can protect people from this preventable malignancy."
To put the mesothelioma risk in perspective, the disease kills about the same number of Americans each year as passive smoking. About 2,500 people a year die from mesothelioma in the United States, according to National Institute of Occupational Safety and Health statistics. About 3,000 deaths a year are attributed to exposure to secondhand tobacco smoke, according to U.S. Environmental Protection Agency statistics.
Ultramafic rock is distributed throughout the Sierra Nevada, Coast Ranges and Klamath Mountains in Northern and Central California, and has been a source of increasing concern as new housing developments cut through these areas. Of most concern are the areas of ultramafic rock associated with tremolite asbestos.
In their ambitious study, Schenker and his colleagues used California Cancer Registry data to identify 2,908 cases of malignant mesothelioma diagnosed between 1988 and 1997 in adults ages 35 and older. In most cases, the registry also provided occupational history. As a control group, an equal number of age- and gender-matched pancreatic cancer cases was selected (since pancreatic cancer has no known association to asbestos exposure). For both the mesothelioma and pancreatic cancer cases, the researchers employed sophisticated geographic information system mapping to pinpoint home or street addresses for every diagnosed individual. A map from the California Department of Conservation, Division of Mines and Geology, served as the reference for ultramafic rock deposits. Finally, statistical adjustments were made for sex, occupational asbestos exposure and age at diagnosis.
The researchers found that the risk of developing malignant mesothelioma was directly related to residential proximity to a source of ultramafic rock. Specifically, the odds of having mesothelioma fell by 6.3 percent for every 10 kilometers (about 6.2 miles) farther a person lived from the nearest asbestos source. The association was strongest in men, but was also seen in women. No such association showed up in the pancreatic cancer group. The study was not designed to determine the "ground zero" risk for those living closest to an asbestos source - only to test for a relationship between proximity and risk.
"This is very creative, painstaking epidemiology," said Jerrold L. Abraham, professor and director of environmental and occupational pathology at SUNY Upstate Medical University in Syracuse, New York, and a leading authority on mesothelioma. "The UC Davis researchers have shown a significant association between living near deposits of naturally occurring asbestos and mesothelioma. This is the strongest evidence possible without conducting one-on-one interviews with each diagnosed mesothelioma patient or his or her family."
Laurel Beckett, professor and vice chair of the UC Davis Department of Public Health Sciences and a study co-author, said the findings are important. "We showed that breathing asbestos in your community is not magically different from breathing asbestos in an industrial setting. It would have been a surprise to find otherwise."
Similarly, she said, it was no real surprise to scientists when passive smoking was found to cause lung cancer. "Like smoking, exposure to asbestos appears to be very dose-dependent," Beckett said. "Day-in, day-out occupational exposures are more dangerous than intermittent exposures in the community. But the more you can do to reduce your personal exposure, the safer you will be."
While the overall mesothelioma rate was about one case per 100,000 people per year in the California study, the rate varied markedly by gender and age. For white males, the rate was 2.29 cases per 100,000. For white females, it was 0.49. People over age 60 had ten times the rate of those ages 40 to 59.
Worldwide, epidemiological studies of mesothelioma have found occupational causes for most but not all cases of the disease. In some undeveloped areas of the world, including parts of Greece and Turkey, mesothelioma cases have been linked to use of naturally occurring asbestos in household materials such as whitewash. The UC Davis study suggests naturally occurring asbestos also causes mesothelioma in developed countries, through incidental, non-occupational exposures.
California has required statewide cancer reporting since 1985 and established the California Cancer Registry in 1988. One of the largest cancer databases in the world, the registry is responsible for collecting cancer incidence and mortality statistics for more than one tenth of the United States population. An estimated 98.9 percent of all mesothelioma cases diagnosed in California are reported to the registry.
The registry's size enabled researchers to identify an association that might not have been apparent in a smaller study.
Needed now are field studies to more accurately characterize determinants of exposure to asbestos fibers among residents in areas with naturally occurring asbestos, Schenker said. In addition, he said more must be learned about the types and size of fibers in asbestos deposits, the types of human activities that disturb asbestos fibers and the determinants of cancer risk in exposed populations.
"Because mesothelioma takes 20 to 30 years to develop, what we learn today will allow us to protect Californians from this preventable cancer decades into the future," Schenker said.
Asbestos Disease Projections Too Low
Current predictions of the future incidence of asbestos-related disease have been substantially underestimated, according to new modelling to be presented in Melbourne today by an epidemiologist from The Australian National University.
The analysis by Dr Mark Clements, from the National Centre for Epidemiology and Population Health, and colleagues shows that the peak number of cases of mesothelioma, a deadly cancer caused by asbestos, will occur four years later and the future total incidence may be in excess of 35 per cent higher than existing models would have predicted. The pattern for mesothelioma reflects changes in asbestos exposure and therefore reflects predictions for all asbestos-related diseases, Dr Clements said. These early results have important implications for asbestos-related disease liability schemes, Dr Clements said, although more detailed work is needed to properly integrate other factors related to the actuarial implications.
According to the research, an existing model developed by the auditing firm KPMG gave the peak of mesothelioma cases as occurring in 2010, with 3530 cases in New South Wales men. However, Dr Clements said their own epidemiological model showed that the peak could occur as late as 2017 and see 6430 cases of the deadly disease in NSW men.
“There is reasonable evidence that the peak of mesothelioma incidence is later than 2010. This has far reaching consequences for actuarial predictions, where the number of cases out to 2060 may be in excess of 35 per cent higher than the number predicted by KPMG’s model,” he said.
“It is unclear why the two models give different results. The KPMG modeling may have been influenced by a common belief that peak incidence would be in 2010; in contrast, our epidemiological model is able to predict the peak for incidence.
“Although these results have implications for liability, there are several steps between predicting mesothelioma incidence and calculating liability,” he said. “Moreover, modelling would be required for other asbestos-related diseases.
“I can’t speculate as to the revised level of liability. However based on our modelling of future mesothelioma incidence it’s worrying that the liability may have been substantially under-estimated,” Dr Clements said.
Dr Clements presented this paper at the Accident Compensation Seminar, hosted by the Institute of Actuaries of Australia.
The analysis by Dr Mark Clements, from the National Centre for Epidemiology and Population Health, and colleagues shows that the peak number of cases of mesothelioma, a deadly cancer caused by asbestos, will occur four years later and the future total incidence may be in excess of 35 per cent higher than existing models would have predicted. The pattern for mesothelioma reflects changes in asbestos exposure and therefore reflects predictions for all asbestos-related diseases, Dr Clements said. These early results have important implications for asbestos-related disease liability schemes, Dr Clements said, although more detailed work is needed to properly integrate other factors related to the actuarial implications.
According to the research, an existing model developed by the auditing firm KPMG gave the peak of mesothelioma cases as occurring in 2010, with 3530 cases in New South Wales men. However, Dr Clements said their own epidemiological model showed that the peak could occur as late as 2017 and see 6430 cases of the deadly disease in NSW men.
“There is reasonable evidence that the peak of mesothelioma incidence is later than 2010. This has far reaching consequences for actuarial predictions, where the number of cases out to 2060 may be in excess of 35 per cent higher than the number predicted by KPMG’s model,” he said.
“It is unclear why the two models give different results. The KPMG modeling may have been influenced by a common belief that peak incidence would be in 2010; in contrast, our epidemiological model is able to predict the peak for incidence.
“Although these results have implications for liability, there are several steps between predicting mesothelioma incidence and calculating liability,” he said. “Moreover, modelling would be required for other asbestos-related diseases.
“I can’t speculate as to the revised level of liability. However based on our modelling of future mesothelioma incidence it’s worrying that the liability may have been substantially under-estimated,” Dr Clements said.
Dr Clements presented this paper at the Accident Compensation Seminar, hosted by the Institute of Actuaries of Australia.
Workers Exposed To Libby Vermiculite Ore Have High Rate Of Chest Wall Abnormalities
More than one-quarter of tested workers at an Ohio manufacturing plant historically exposed to asbestos-containing vermiculite ore exhibited signs of scarring of the chest wall lining, a study by researchers from the University of Cincinnati has found.
Researchers examined recent chest X-rays of 236 people who worked at a plant in Marysville, Ohio, that until 1980 used vermiculite ore mined in Libby, Mont., that contained asbestos fibers.
Of the 236 workers tested, 62 (26.3 percent) showed pleural plaques, or scarring of the chest wall lining. The occurrence was as high as 44.1 percent in workers with the largest and heaviest exposure to the vermiculite ore. The percentage of workers with pleural plaques was 5.1 percent in those with the lowest levels of exposure.
Pleural plaques are usually considered markers of previous exposure to asbestos fibers. Because of the previous exposure to asbestos, there is a potential increased risk for other asbestos-related lung changes, including scar tissue within the lungs and certain types of cancer such as mesothelioma.
Preliminary results of the study were presented in San Diego May 24, 2005, at the annual International Conference of the American Thoracic Society.
"Our study shows that cumulative exposure to vermiculite from Libby is associated with a significant increase in pleural changes," said study leader James Lockey, MD, professor of occupational and pulmonary medicine at the University of Cincinnati College of Medicine.
"There is clearly a relationship with increasing exposure, but the pleural changes also were seen in the low-exposed workers," said co-author Amy Rohs, MD, a fellow in occupational and pulmonary medicine at University of Cincinnati.
About 0.2 percent of the general population with minimal history of exposure to respiratory hazards shows signs of pleural plaques, Dr. Lockey noted. "I was surprised at the significant increase in overall pleural changes in this working population from 2 percent in 1980 to 26 percent, based on these preliminary results," he added.
"The public health implications of these preliminary findings are important in view of the national distribution of the Libby vermiculite ore," the authors concluded.
Until 1990, more than 200 sites around the country received shipments of vermiculite from the Libby mine.
Vermiculite is a group of minerals with a flaky, mica-like structure. Vermiculite ore from Libby has been shown to contain high levels of asbestos, which could have become airborne and inhaled when used in manufacturing. Vermiculite is widely used in a variety of applications, including insulation, packing materials, construction materials and gardening products. The Libby mine closed in 1990 and vermiculite ore used now comes from other sources and is not known to contain asbestos.
The X-rays were taken during the past two years, and each was reviewed independently by three board-certified radiologists. Spirometry tests, which measure lung function, and health histories also were taken. Although these were not assessed for this study, they will be reported later when the complete study findings are reviewed and published.
The workers were among a group of 513 employees at the Ohio plant exposed to vermiculite and who took part in a 1980 study. Of these 513 workers, 433 (84 percent) are currently alive. That original study, published by Dr. Lockey in the June 1984 issue of American Review of Respiratory Disease, initially showed that exposure to vermiculite containing asbestos fibers could cause pleural plaques.
Researchers examined recent chest X-rays of 236 people who worked at a plant in Marysville, Ohio, that until 1980 used vermiculite ore mined in Libby, Mont., that contained asbestos fibers.
Of the 236 workers tested, 62 (26.3 percent) showed pleural plaques, or scarring of the chest wall lining. The occurrence was as high as 44.1 percent in workers with the largest and heaviest exposure to the vermiculite ore. The percentage of workers with pleural plaques was 5.1 percent in those with the lowest levels of exposure.
Pleural plaques are usually considered markers of previous exposure to asbestos fibers. Because of the previous exposure to asbestos, there is a potential increased risk for other asbestos-related lung changes, including scar tissue within the lungs and certain types of cancer such as mesothelioma.
Preliminary results of the study were presented in San Diego May 24, 2005, at the annual International Conference of the American Thoracic Society.
"Our study shows that cumulative exposure to vermiculite from Libby is associated with a significant increase in pleural changes," said study leader James Lockey, MD, professor of occupational and pulmonary medicine at the University of Cincinnati College of Medicine.
"There is clearly a relationship with increasing exposure, but the pleural changes also were seen in the low-exposed workers," said co-author Amy Rohs, MD, a fellow in occupational and pulmonary medicine at University of Cincinnati.
About 0.2 percent of the general population with minimal history of exposure to respiratory hazards shows signs of pleural plaques, Dr. Lockey noted. "I was surprised at the significant increase in overall pleural changes in this working population from 2 percent in 1980 to 26 percent, based on these preliminary results," he added.
"The public health implications of these preliminary findings are important in view of the national distribution of the Libby vermiculite ore," the authors concluded.
Until 1990, more than 200 sites around the country received shipments of vermiculite from the Libby mine.
Vermiculite is a group of minerals with a flaky, mica-like structure. Vermiculite ore from Libby has been shown to contain high levels of asbestos, which could have become airborne and inhaled when used in manufacturing. Vermiculite is widely used in a variety of applications, including insulation, packing materials, construction materials and gardening products. The Libby mine closed in 1990 and vermiculite ore used now comes from other sources and is not known to contain asbestos.
The X-rays were taken during the past two years, and each was reviewed independently by three board-certified radiologists. Spirometry tests, which measure lung function, and health histories also were taken. Although these were not assessed for this study, they will be reported later when the complete study findings are reviewed and published.
The workers were among a group of 513 employees at the Ohio plant exposed to vermiculite and who took part in a 1980 study. Of these 513 workers, 433 (84 percent) are currently alive. That original study, published by Dr. Lockey in the June 1984 issue of American Review of Respiratory Disease, initially showed that exposure to vermiculite containing asbestos fibers could cause pleural plaques.
How Asbestos Fibers Trigger Cancer In Human Cells
University scientists believe they are the first in the world to study the molecular underpinnings of cancer by probing individual bonds between an asbestos fiber and human cells.
Though any clinical application is years away, the researchers hope their findings could aid in drug development efforts targeting illnesses caused by excessive exposure to asbestos, including the deadly cancer called mesothelioma.
The researchers use atomic force microscopy to observe how a single asbestos fiber binds with a specific receptor protein on cell surfaces. They suspect that at least one of the more lethal forms of asbestos triggers a cascade of events inside cells that eventually lead to illness, sometimes decades later.
The conditions most commonly associated with long-term exposure to airborne asbestos are lung cancer; asbestosis, a chronic respiratory disease; and mesothelioma, a cancer that forms in the membrane lining most internal organs of the body, including the lungs.
Eric Taylor, a doctoral candidate in earth sciences at Ohio State and a coauthor of the study, describes atomic force microscopy as “Braille on a molecular level,” meaning it allows scientists to feel and observe what’s happening on molecular surfaces.
“We’re looking at what molecules are involved in the chain of events when the fiber touches the cell. Does the binding occur over minutes, or hours? And what processes are triggered?” said Taylor, who presented the research at the American Geophysical Union meeting in San Francisco.
Asbestos comprises six different minerals that naturally occur in both fragment and fibrous forms. Because of its high durability and heat resistance, the fibrous form has been used in many manufacturing products since the late 1800s. Though its use is now highly regulated, asbestos is still present in many materials. The U.S. Department of Labor estimates that 1.3 million employees face significant asbestos exposure on the job. Environmental exposure is also possible because asbestos is a naturally occurring mineral in soils and exposed bedrock.
Crocidolite, or blue asbestos, is part of the amphibole group of asbestos minerals, which were banned in most of the Western world by the mid-1980s. Before that, they were used in such products as ceiling tiles and thermal insulation.
Ohio State researchers have focused so far on the crocidolite form of asbestos, but eventually hope to study how all six forms of asbestos interact with certain proteins on cell surfaces. Some forms of asbestos can dissolve in the lungs if they are inhaled, but others are believed to essentially “stick” to cells, especially at high concentrations, and eventually cause lung diseases.
“For the first time, this will give us data on biological activity that should help policymakers determine which forms of asbestos are the most dangerous,” said Steven Lower, associate professor of earth sciences at Ohio State and a coauthor on the study.
“The hypothesis we’re testing is that binding of cell surface receptors to asbestos fibers triggers a signal event, which initiates the cancer,” said Lower, also a faculty member in the School of Environment and Natural Resources. “There seems to be something intrinsic about certain types of asbestos, blue asbestos in particular, that elicits a unique signal, and it triggers inflammation, the formation of pre-malignant cells and, ultimately, cancer.”
The first protein to be studied is epidermal growth factor receptor, which is present on the surface of every human cell. Understanding the intricacies of the binding process between the mineral and one or more proteins will provide an index of the biological activity of a particular type of asbestos, and might lead the researchers to figure out how to prevent or undo that interaction, Lower said.
Taylor said the driving motivation behind the research is the potential to find a way to intervene and prevent illness even after someone is exposed to asbestos. Mesothelioma symptoms don’t typically appear until 30 to 50 years after exposure. After diagnosis, however, the cancer is difficult to control, and there is no cure.
This work is supported by the National Science Foundation.
Taylor and Lower conducted the research with Ann Wylie of the University of Maryland and Brooke Mossman of the University of Vermont.
Though any clinical application is years away, the researchers hope their findings could aid in drug development efforts targeting illnesses caused by excessive exposure to asbestos, including the deadly cancer called mesothelioma.
The researchers use atomic force microscopy to observe how a single asbestos fiber binds with a specific receptor protein on cell surfaces. They suspect that at least one of the more lethal forms of asbestos triggers a cascade of events inside cells that eventually lead to illness, sometimes decades later.
The conditions most commonly associated with long-term exposure to airborne asbestos are lung cancer; asbestosis, a chronic respiratory disease; and mesothelioma, a cancer that forms in the membrane lining most internal organs of the body, including the lungs.
Eric Taylor, a doctoral candidate in earth sciences at Ohio State and a coauthor of the study, describes atomic force microscopy as “Braille on a molecular level,” meaning it allows scientists to feel and observe what’s happening on molecular surfaces.
“We’re looking at what molecules are involved in the chain of events when the fiber touches the cell. Does the binding occur over minutes, or hours? And what processes are triggered?” said Taylor, who presented the research at the American Geophysical Union meeting in San Francisco.
Asbestos comprises six different minerals that naturally occur in both fragment and fibrous forms. Because of its high durability and heat resistance, the fibrous form has been used in many manufacturing products since the late 1800s. Though its use is now highly regulated, asbestos is still present in many materials. The U.S. Department of Labor estimates that 1.3 million employees face significant asbestos exposure on the job. Environmental exposure is also possible because asbestos is a naturally occurring mineral in soils and exposed bedrock.
Crocidolite, or blue asbestos, is part of the amphibole group of asbestos minerals, which were banned in most of the Western world by the mid-1980s. Before that, they were used in such products as ceiling tiles and thermal insulation.
Ohio State researchers have focused so far on the crocidolite form of asbestos, but eventually hope to study how all six forms of asbestos interact with certain proteins on cell surfaces. Some forms of asbestos can dissolve in the lungs if they are inhaled, but others are believed to essentially “stick” to cells, especially at high concentrations, and eventually cause lung diseases.
“For the first time, this will give us data on biological activity that should help policymakers determine which forms of asbestos are the most dangerous,” said Steven Lower, associate professor of earth sciences at Ohio State and a coauthor on the study.
“The hypothesis we’re testing is that binding of cell surface receptors to asbestos fibers triggers a signal event, which initiates the cancer,” said Lower, also a faculty member in the School of Environment and Natural Resources. “There seems to be something intrinsic about certain types of asbestos, blue asbestos in particular, that elicits a unique signal, and it triggers inflammation, the formation of pre-malignant cells and, ultimately, cancer.”
The first protein to be studied is epidermal growth factor receptor, which is present on the surface of every human cell. Understanding the intricacies of the binding process between the mineral and one or more proteins will provide an index of the biological activity of a particular type of asbestos, and might lead the researchers to figure out how to prevent or undo that interaction, Lower said.
Taylor said the driving motivation behind the research is the potential to find a way to intervene and prevent illness even after someone is exposed to asbestos. Mesothelioma symptoms don’t typically appear until 30 to 50 years after exposure. After diagnosis, however, the cancer is difficult to control, and there is no cure.
This work is supported by the National Science Foundation.
Taylor and Lower conducted the research with Ann Wylie of the University of Maryland and Brooke Mossman of the University of Vermont.
Subscribe to:
Posts (Atom)
