BRCA1 has been shown to be closely linked to the risk of breast cancer and a number of other malignancies. But a new study out of Ireland suggests that there may also be a connection between BRCA1 expression and sensitivity to vinorelbine, an antimitotic chemotherapy drug, in mesothelioma tumors. Classified as a plant alkaloid, vinorelbine attacks tumor cells by interfering with their ability to properly divide the chromosomes in their nuclei (mitosis).

To test the connection between BRCA1 and vinorelbine sensitivity in mesothelioma, the researchers tested 144 mesothelioma tissue specimens for their level of BRCA1 expression.  They found that 38.9% of the samples exhibited a loss of BRCA1 protein expression which was directly correlated with lower vinorelbine resistance. The opposite was also true: The team confirmed “the reactivation of vinorelbine induced apoptosis (cell death) following re-expression of BRCA1 in resistant cells.”

Currently, there are a limited number of therapeutic options for mesothelioma, which is caused by inhaling or ingesting asbestos and mesothelioma tends to spread quickly once it takes hold. Chemotherapy is often a primary treatment modality, but choosing the right drug is key since, as this study demonstrates, individual mesothelioma patients respond differently to different drugs. Genetic studies like this one could eventually allow doctors to customize mesothelioma treatments based on the results of a simple blood test.

In a report of their findings in the Journal of Pathology, the researchers from the Centre for Cancer Research and Cell Biology at Queens University in Belfast concluded, “This data suggests BRCA1 plays a critical role in mediating apoptosis (cell death) by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker.”

source form: survivingmesothelioma

Scientists with the Cancer and Leukemia Group B (CALGB), a research team based at the University of California, have ruled out further study on the medication as a single agent (administered by itself) after a phase II trial found no significant survival benefit among mesothelioma patients.

Vatalanib is an oral medicine classified as an anti-angiogenesis drug, designed to inhibit the formation of new blood vessels necessary to ‘feed’ a growing tumor. Although vatalanib has shown promise in the treatment of non-small cell lung cancer and has been compared to Avastin (bevacizumab), another anti-angiogenesis drug being tested for mesothelioma, the new study shows vatalanib by itself is not effective.

Phase II trials test the safety and efficacy of a new drug in human patients.  To test vatalanib in mesothelioma patients, researchers at 19 centers enrolled a total of 47 patients. The median age was 75 and most (77%) had the epithelioid variety of mesothelioma. Patients received 1250 mg of vatalanib orally once a day.  To test their response, CT scans and blood tests were performed at the start of the study and every six weeks afterward.

Toxicity was generally mild with the most common side effect – nausea – occurring in only 15% of patients.  Unfortunately, the effects were also mild.  Only 6% of the mesothelioma patients showed even a partial response to the drug.  Fifty-five percent of patients had 3 months of progression-free survival and the median overall survival of mesothelioma patients in the study was 10 months – not enough, say the researchers, to recommend vatalanib over other treatments.

In a summary of their findings published recently in the journal Lung Cancer, the study’s authors conclude, “Vatalanib as a single agent with this dose and schedule does not warrant further study in this disease (mesothelioma).”  Other  anti-angiogenesis drugs are being tested in mesothelioma patients and at least one intravenous drug has shown some promise.

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That warning comes directly from the Environmental Protection Agency (EPA) which admits to having done exactly that when it experimented with relaxing some of its own regulations for safe asbestos handling. EPA began regulating asbestos use after the material was linked to mesothelioma and a range of other health problems in the 1960’s. Airborne asbestos fibers can lodge in the lungs, triggering mesothelioma even decades after exposure.

Despite the danger, beginning in 1999, EPA considered alternative methods to “augment” the Asbestos National Emission Standards for Hazardous Air Pollutants, the act that governs asbestos handling during demolition. The alternative methods considered, including the Fort Worth Method and the Alternative Asbestos Control Method, leave some or all of the asbestos-containing material in place and allow demotion equipment to shred it.  The material is wetted during demotion in an attempt to limit the release of fibers and lower the risk of mesothelioma.

But, in the recent statement, EPA Inspector General Arthur A. Elkins, Jr. said such methods still have the potential to stir up airborne asbestos and should, therefore, not have been considered. EPA’s Office of Research and Development ended the research project in July 2011 but apparently not all contractors have heard the message.

“Our preliminary research indicates that unapproved methods are currently being used or considered at multiple sites,” wrote Elkins in the statement.  “The use of unapproved methods is counter to EPA regulations and… may jeopardize the health and safety of the public.” Among the sites where such unapproved methods may be used are the Hanford Superfund Site near Richland, Washington and a gaseous diffusion plant demolition in Paducah, Kentucky.

Video surveillance of these and other sites show government employees and contractors working without the required protective gear, raising their risk for mesothelioma and other asbestos related diseases.  And because settled dust results indicated that asbestos fibers did escape the restricted areas, workers and members of the public who were adjacent to these sites during demotion could also be at higher risk for mesothelioma. The director’s statement calls on all sites using “unapproved methods” for asbestos demolition to stop and to notify potentially exposed workers and members of the public of their asbestos risk.

Tens of thousands of older homes and public buildings still contain asbestos.  To reduce the risk of mesothelioma, EPA recommends that homeowners hire professional asbestos abatement teams to remove asbestos prior to demolition or remodeling.  Mesothelioma is an aggressive cancer that may be diagnosed decades after asbestos exposure.

source form: survivingmesothelioma

But according to Kara Franke and Dennis Paustenbach who examined dozens of published and unpublished documents on asbestos knowledge from 1900 to 1970, the Navy understood the health hazards of asbestos as early as the 1930’s. Although they continued to require its use on ships, the Navy also recommended certain precautions for safe handling of the material.  After mesothelioma was clearly linked to asbestos in the 1960’s, the ChemRisk researchers say the Navy “attempted to implement procedures that would minimize the opportunity for adverse effects on both servicemen and civilians.”

Despite those precautions, it was too little, too late for many servicemen.  Mesothelioma can take as long as 40 years to develop after asbestos exposure, meaning that many veterans had already set the stage for the disease from asbestos exposure during the 1940’s and 1950’s. Thousands of people working in other industries were also exposed to mesothelioma-causing asbestos because their employers were either unaware, or chose to ignore, the growing evidence of the material’s toxicity and carcinogenicity.

Published in the journal Inhalation Toxicology, Franke and Paustenbach’s study found that, by as early as 1930, “it was clear that occupational exposure to asbestos caused a unique disease (asbestosis)”. Understanding of asbestos increased steadily between about 1938 and 1965 during which time “a considerable amount of exposure and epidemiology data was collected” by private and government scientists. Franke and Paustenbach’s study was recently presented at the 21st annual International Society of Exposure Science meeting in Baltimore. Maryland.

In the U.S., about 2,500 people each year are diagnosed with mesothelioma, a cancer of the lung and abdominal lining that typically carries a poor prognosis.  Standard treatment for mesothelioma includes chemotherapy (alimta and cisplatin or carboplatin), surgery (where appropriate), and radiation in some cases.  Today, multi-modality treatments, immune therapies and gene therapies are being investigated as potential therapeutic modalities for mesothelioma victims.

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CBP501, produced by the Japanese Drug company CanBas, is a novel synthetic peptide that seems to enhance the effectiveness of cisplatin by acting on multiple pathways that govern the lifecycle of cells and the natural repair of DNA damage. By modulating the production of a certain enzyme, it allows mesothelioma cells to become more susceptible to the damaging effects of platinum (cisplatin) build-up. At the same time, it prevents the cells from properly repairing themselves. The drug has also shown the ability to resensitize mesothelioma cells that have become resistant to cisplatin.

The FDA’s ‘orphan drug’ designation is reserved for medications that address rare (fewer than 200,000 patients) and hard-to-treat illnesses like mesothelioma, for which treatment options are limited. As an orphan drug, CBP501 will be exempt from certain FDA fees and requirements, making it easier to bring it to market for mesothelioma patients sooner. Right now, treatments and research for mesothelioma and other rare diseases lags behind those affecting a larger percentage off the population, such as diabetes and heart disease.

Mesothelioma is a rare cancer of the mesothelium, the sac that encases the lungs and other organs. It is almost always caused by exposure to asbestos and often occurs 20 to 40 years after that exposure.  Because it is so aggressive, mesothelioma is usually treated using a multi-modal approach that includes chemotherapy. While the combination of cisplatin and pemetrexed is more effective than other drugs, most mesothelioma patients are still facing an uphill battle.  The median survival for mesothelioma is 16 months, according to the National Cancer Institute.

CBP501 is in the late stages of Phase II clinical trials for first-line treatment of malignant pleural mesothelioma for patients who are not eligible for curative surgery. Sixty-three mesothelioma patients have been enrolled in that trial which the company says should be completed in the first half of 2012.

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Historically, those who mine the raw material are at greatest risk for mesothelioma, along with those who work in construction or in manufacturing asbestos-containing products. Inhaled fibers can cause irritation and inflammation that can trigger mesothelioma and other asbestos related diseases even decades after exposure.

Because higher concentrations of airborne asbestos increase the health risk, workplace monitoring of airborne asbestos is required to help protect workers from mesothelioma and other diseases.  Phase contrast microscopy (PCM) is one of the most common methods used. With PCM, a sample is collected on a mixed cellulose ester membrane filter which is then cleared with a chemical solution and the collected fibers are counted under 400x magnification.  But PCM requires a high degree of sophistication on the part of the microscopist performing the test.  It is also not capable of distinguishing between asbestos and non-asbestos fibers, so all the fibers that meet the counting criteria are counted as asbestos.

Now a group of mechanical engineers in South Korea have developed a an automated system using high-throughput microscopy (HTM) that they say can quickly and accurately distinguish asbestos fibers from other particles on a sample slide. To test the effectiveness of the HTM system, the researchers used the method to measure known concentrations of airborne asbestos at 11 different workplaces where asbestos is used.  The results showed “a reasonably good agreement in the asbestos concentration” when compared with conventional testing methods. Because of HTM’s accuracy and higher efficiency, the team suggests that it be considered as an alternative to conventional PCM for preventing mesothelioma and other asbestos related diseases through onsite workplace monitoring.

Mesothelioma is a particularly difficult cancer to treat and nearly all cases would have been avoidable if asbestos had been previously removed from products and workplaces.  The fact that asbestos is still ubiquitous means that people of all ages are still being potentially exposed to this mesothelioma-causing carcinogen.  New automated tests like HTM may help protect workers from being diagnosed with mesothelioma in the future.

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In 2004, pemetrexed was the first medicine approved by the FDA specifically for the treatment of malignant mesothelioma.  It has since also been approved for the treatment for small cell lung cancer.  While it has been hailed as a breakthrough mesothelioma drug, and has become the gold standard for chemotherapeutic treatment of the disease, pemetrexed also has many serious side effects including low white blood cell counts, low blood platelets, anemia, fatigue and nausea.

In addition, pemetrexed does not work for all mesothelioma patients.  The ability to predict which patients are most likely to respond could spare some patients the serious side effects of pemetrexed and help steer their doctors in a more effective treatment direction.

To conduct their study, the Chicago-based research team used quantitative trait loci (eQTL) mapping combined with drug-induced cytotoxicity data to measure the connections between genes and pemetrexed susceptibility for mesothelioma and lung cancer.  They found that the expression of two genes in particular – CTTN and ZMAT3 – accounted for more than 30 percent of the cases of pemetrexed resistance.  The findings were confirmed using a different type of assay.  Conversely, when gene expression of CTTN or ZMAT3 was suppressed, there was a decrease in cell survival – an indication that the pemetrexed was working.

The results could eventually lead to a simple blood test for expression of CTTN or ZMAT3 to predict the likely response of individual mesothelioma patients to pemetrexed.  While the study has important implications for mesothelioma patients, the researchers say it could also be used to improve the treatment of other cancers.

In a summary of their findings the authors concluded that their study further supports the use of genetic determinants for chemotherapeutic susceptibilities for mesothelioma and other diseases.

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Mesothelioma is caused almost exclusively by inhalation or ingestion of asbestos fibers and is notoriously resistant to most conventional treatments. Within the last decade, chemotherapy with cisplatin-antifolate combinations has been shown to improve responses and prolong survival.  Based on the successes shown in clinical trials, a trio of research scientists in The Netherlands launched their own population-based study to “assess the impact of this development on clinical practice and survival at a population-based level.”

The study focused on 4,731 Dutch patients diagnosed with mesothelioma between 1995 and 2006. For the periods 1995-1998 and 2005-2006, the use of chemotherapy to treat mesothelioma jumped from 8% to 36%.  At the same time, median survival for chemotherapy-treated patients increased from 10.1 months in earlier years to 13.1 months in more recent years.

Median survival was still poor (3.9 months) for peritoneal mesothelioma patients, although it was better for women and younger patients.  In summarizing their findings for the European Respiratory Journal, the authors write, “This study demonstrates that chemotherapy use increased at a national level and coincided with an improvement in survival.” While this increase is most likely an indication of the effectiveness of the novel chemotherapy, the authors caution that “due to the observational nature of this study, alternative explanations cannot be excluded.” In addition, the increase in mesothelioma survival was relatively modest.

Cisplatin is a platinum-based chemotherapy drug marketed as Platinol and used to treat a number of different cancers, including mesothelioma, some carcinomas such as small cell lung cancer and ovarian cancer, lymphomas and germ cell tumors.  Inside cancer cells, cisplatin and other platinum-based drugs (such as carboplatin) cause crosslinking of the of DNA and trigger apoptosis (cell death).

In the U.S., cisplatin is usually combined with the antifolate drug pemetrexed (Alimta) for treating mesothelioma. Antifolate drugs block the activity of folic acid inside cells interfering with cellular metabolism. Pemetrexed was first developed in 2001 and was approved by the U.S. Food and Drug Administration (FDA) for the treatment of mesothelioma in 2004.

source form: survivingmesothelioma

He never has been more optimistic.

Hassan, a senior investigator at the National Cancer Institute, has opened two new clinical trials for patients who already have received standard care that has failed to be effective.

Both trials involve immunotoxins, a human-made protein that includes a targeted portion linked to a toxin designed to kill the cancer cells. Mesothelioma is the cancer caused by an exposure to sbestos.

The first is a study of Pentostatin plus Cyclophosphamide immune depletion. It is for patients with tumors that are not eligible for curative surgical resection. To be eligible for the trial, a patient must have been previously treated with at least one platinum-containing chemotherapy round.

Each treatment cycle in the study — patients can receive up to three — will consist of Pentostatin intravenously, Cyclophosphamide pills and SS1P, also taken intravenously.

The second new trial is a dose escalation study of BAY94-9343, an antibody drug conjugate, to find the maximum tolerated dose. It is aimed at patients with an advanced solid tumor that has not responded to standard therapy.

Each treatment will consist of BAY94-9343 given intravenously every 21 days. Cycles will continue for as long as there is no progressive disease or unacceptable toxicity.

“There is a better understanding of this disease and the treatment options than there ever has been,” Hassan said in a recent interview with the Mesothelioma Center. “I’m confident in the recent advances, and we’ll continue to learn more with these trials.”

In addition to these latest Phase I trials, Hassan also has been overseeing a Phase II study of IMC-A12, or cixutumumab, an antibody that has shown considerable promise in treating mesothelioma patients.

The advantage of participating in a trial at the National Cancer Institute can be substantial. There is no charge for medical care. And the NCI trials are open to anyone, regardless of where they live in the United States.

Patients are responsible for travel costs for the initial screening, but if they are accepted into the trial, they will be reimbursed for all subsequent visits if they live outside the area.

“A rare disease (like mesothelioma) can make it difficult to conduct big trials, but there is no better place to do them,” Hassan said. “We’re moving in the right direction.”

source form: asbestos

Large amounts of dust in the air was first noticed by the firefighters, which then sparked testing of the air samples. That led to the evacuation.

On Monday, firefighters spoke at Lackawanna City Council meeting, voicing their concern about getting the situation properly corrected and ensuring that their health is not in danger.Asbestos exposure is believed to be caused from abatement work conducted back in November on the building’s piping and boiler system.

“We should’ve been out of the firehouse immediately upon knowing there were dangerous levels of asbestos present,” said Thomas R. Mendez, president of Local 3166, Lackawanna Professional Firefighters Association.

The firemen are concerned because of the known danger that asbestos exposure causes. Since the 1960s, it has been proven that this exposure can cause mesothelioma, a rare cancer of the lining of the lungs, in addition to other asbestos-related diseases. Because of the fatal nature of this disease, frequent diagnostic testing is recommended to those who may have potentially been exposed.

Lackawanna firefighters will likely be encouraged to receive testing for exposure because of the severity of the air sample test results. According to Lt. James J. Fino, the test results showed “astronomical levels of asbestos.”

“It’s a huge concern for all of our members. We’ve been in there up until Saturday.”

In the line of public service, asbestos exposure is not a rare occurrence for firemen. As it may come at little comfort to the fire team of Lackawanna, their occupation does involve interaction with asbestos more often than they would like.

Asbestos and Firefighters

Between the frequent dangers of entering fire-blazing buildings that are often constructed with asbestos, to using potentially asbestos-containing materials on a daily basis, to the reality that many firehouses themselves are constructed with the toxic material, these workers are undoubtedly at an increased risk of health issues. This has become evident through countless events in recent history.

One of the most notable cases of firefighters being exposed to increased amounts of asbestos involves a day that our nation will never forget: September 11, 2001. Immediately after the attack on the World Trade Center, first responders quickly rushed into the scene, many of whom were firefighters, policemen and first-aid workers.

Because asbestos was widely used in the lower stories of the World Trade Center, asbestos fibers quickly became airborne as the towers collapsed. These responders rushed into the scene and remained there throughout the rescue and recovery efforts where large amounts of these toxic fibers were ingested. The hazard came immediately and affected some within very short periods of time.

Beyond the 9/11 attacks, firefighters often face additional dangers, including rescues they perform on a regular basis. Just as the toxic substance was used in large buildings and structures, it was also frequently used to construct homes and offices.

When these structures become inflamed, firemen are at risk if the asbestos gets disturbed and the fibers become airborne. This applies to residential homes and places where the majority of their work is conducted. While they perform their duty to put out the fire, they may very well be inhaling toxic dust.

Recent events have spawned some to look more carefully at the work environment of our servicemen. According to a 2010 news story, dozens of firefighters from Everett, Washington, filed claims against the city seeking $9 million because the city allowed the men to conduct training exercises in buildings with known asbestos-contaminants.

The buildings were owned by the city and therefore were used for training purposes, despite the fact that some officials knew the building contained toxic substances. The firemen and their family were reportedly not suing for cash, but more so for the city to cover lifetime medical expenses related to the monitoring of asbestos-related health issues.

Other unfortunate circumstances where firemen may be at increased risk of asbestos exposure include their daily interaction with their equipment. Asbestos was widely used because of its insulating and heat-resistant properties. For firefighting, these characteristics are extremely useful. Therefore, prior to the discovery of the link between asbestos and cancer, firefighting equipment manufacturers often included asbestos in products like gloves and protective clothing.

During situations where the asbestos in these equipment pieces become disturbed, the fibers again become airborne and toxic to those who inhale it. Unfortunately, through the continuous and physical nature of the job, it is likely that this equipment will become damaged and will therefore potentially cause asbestos fibers to entire the air.

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