AboutMesothelioma.Net

First Time Federal Funding For Mesothelioma Research

Thursday, January 24, 2008

Source: Mesothelioma Applied Research Foundation

The Mesothelioma Applied Research Foundation has recently announced that research into mesothelioma is now available for federal funding. When President Bush signed the latest Defense Appropriations bill in mid-November, $50 million was appropriated for the Department of Defense’s (DoD) Peer Reviewed Medical Research Program, which makes money available for medical research that demonstrates “clear scientific merit and direct relevance to military health.” Mesothelioma was, the first time, included among the research priorities for the Medical Research Program. The Meso Foundation is recommending all mesothelioma researchers apply for grants from the program, as future appropriations will be partly-based on the interest shown by current researchers.

Mesothelioma, especially pleural mesothelioma, has a long history of affecting military men and women. Navy veterans have been especially hard-hit by the disease. To learn more about the Navy and mesothelioma, please read the following article, Navy & Maritime Ships with Asbestos, or view the following website: www.mesotheliomafromnavy.com.
(Link will open in a new window.)

Labels: mesothelioma

posted by Belluck & Fox at 3:27 PM
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NICE Gives Green Light to Treatment for Asbestos-Induced Lung Cancer

Source: Medical News Today

The United Kingdom’s National Institute for Health and Clinical Excellence (NICE) has recently issued guidelines for the use and administration of Alimta therapy for UK residents with mesothelioma. NICE is the independent organization responsible for providing guidance on the promotion of good health and the prevention and treatment of ill health for the UK.

The NICE guidelines dictate that Alimta is to be used only for patients with a current “World Health Organization performance status of 0 or 1, who are considered to have advanced disease and for whom surgical resection is considered inappropriate.” With NICE’s recommendation now official, patients under the care of the National Health System will be able to receive Alimta if they are eligible for it. The issuance of the guidelines caps a two-and-a-half-year process of filings and appeals to bring what is considered the best drug available for the treatment of pleural mesothleioma to British patients who need it.

Note: The article linked from this page identifies mesothelioma as a form of lung cancer. While common to do so, this is incorrect. Mesothelioma and lung cancer are very different forms of cancer. To learn more about the differences between mesothelioma and lung cancer, please read the following article: mesothelioma and lung cancer.

Labels: mesothelioma

posted by Belluck & Fox at 2:45 PM
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Swedish Experience with Peritonectomy and HIPEC. HIPEC in Peritoneal Carcinomatosis.

Friday, January 18, 2008

Source: Swedish Experience with Peritonectomy and HIPEC. HIPEC in Peritoneal Carcinomatosis.
(Ann Surg Oncol. 2007 Dec 5)

Peritoneal Carcinomatosis refers to the extensive spread of malignant tissue throughout the abdomen (the peritoneum). It is not an individual form of cancer, but is a term used to describe widespread abdominal metastases from other forms of the disease, such as peritoneal mesothelioma or colorectal cancer. Historically, peritoneal carcinomatosis has presented with a poor prognosis and a median survival of about three months, but advances in treatment modalities are offering hope that effective therapies are now available. Doctors from Sweden have recently described their use of peritonectomy and heated intra-peritoneal chemotherapy (HIPEC) to treat a number of patients with peritoneal carcinomatosis. Under certain conditions, their results are very promising.

Introduction to the Study

Peritonectomy refers to the surgical removal of malignant tissues in the peritoneum. There are a number of individual techniques that fall under the peritonectomy framework and the one chosen will be based on the patient’s disease and his or her overall health. Heated intra-peritoneal chemotherapy (HIPEC) is a method of chemotherapy where the chemo agent is heated to 107.6 degrees Fahrenheit (42 degrees Celsius) and then delivered to the abdomen. Heating the chemo agent has three important benefits over standard chemotherapy:

1. Cancer cells are more sensitive to heat than are regular cells and they die-off at 107.6(F)/42(C).
2. The heat increases the cytotoxic power of the chemo agent, making it more powerful and, hopefully, killing more cancerous cells.
3. The added heat softens the actual tumor nodules, which allows more of the chemo agent to be absorbed by the malignant tissues.
   (source: http://www.hipec.org/files/HIPEC.pdf)

When treating peritoneal carcinomatosis, HIPEC is delivered for 90 minutes immediately following the surgery. This allows the chemotherapy to have an immediate impact on the residual tumor cells.

Some earlier studies have shown that the combination of peritonectomy and HIPEC has a positive impact on patient survival time for people with peritoneal carcinomatosis. The Swedish doctors whose study we are discussing here collected data for 103 patients who underwent peritonectomy/HIPEC between 2003 and 2006. The individual cancers represented in the sample were: pseudomyxoma peritonei, colorectal cancer, gastric cancer, ovarian cancer and peritoneal mesothelioma. Only patients with strictly peritoneal disease were enrolled; patients with metastasis to areas outside the abdomen were excluded from the study. The actual chemotherapy agent was adjusted based on the type of cancer involved. The mesothelioma patients received cisplatin and doxorubicin.

Results

The results from the study show promise, but they are not without complication. The authors did not break out the survival rates for each of the individual cancers, but they did show that overall survival averaged 72.3% at 2 years, which is better than previous cohorts of patients with peritoneal carcinomatosis who underwent traditional therapy. The morbidity rate was 56.3%, which they state was high, but comparable to other studies that have investigated peritonectomy/HIPEC. Reasons offered for the high morbidity rate include surgical complications resulting from the interference of scar tissue from previous surgeries, as well as the relatively high doses of chemotherapy that the patients received. Neutropenia, which is condition characterized by an abnormally low number of the most common form of white blood cells (neutrophils), was a common side effect of HIPEC and the authors urge that patients who undergo HIPEC are tested for it. They also urge that patients be treated in isolation to help prevent against the development of an infection that the body will be compromised in fighting due to the lower white blood cell count.

Conclusion

The most important factors that led to a successful treatment with long-term benefits included patients with a strong performance status and those who achieved optimal cytoreduction, i.e., those whose surgery removed all visible tumor tissue. As regards the former condition, the authors concluded that good performance status was a good prognostic factor, but that age was not. They found that patients who were otherwise healthy, even if older, were just as likely to have a strong outcome as those patients with a good performance status who happened to be younger. Because of these findings, the authors recommend that simply using patient age as a weighing factor for this treatment should be avoided.

They felt that optimal cytoreduction was a key component to a successful outcome. Because chemo agents cannot penetrate tumors larger than 2mm, surgeons should attempt to remove all of the visible malignancy. If they cannot remove all of the visible tissue, the HIPEC may not be able to destroy all of the residual cells, which would lead to a return of the cancer. The authors state that in patients with sub-optimal cytoreduction, the use of the procedure is controversial because of the morbidity issues. But for candidates who are otherwise healthy and where optimal cytoreduction is achieved, peritonectomy and HIPEC may be an effective treatment for people with peritoneal carcinomatosis.

Labels: mesothelioma

posted by Belluck & Fox at 3:54 PM
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Current State and Future Directions of Pleural Mesothelioma Imaging

Wednesday, January 16, 2008

Source: Armato III SG, et al., Current state and future directions of pleural mesothelioma imaging, Lung Cancer (2007), doi:10.1016/j.lungcan.2007.09.027

Imaging is one of the most important aspects of cancer diagnostics. It allows the physician team to look at—and respond to—a number of different aspects of a person’s disease, including tumor extent, invasion of distant body spaces, treatment response, as well as a host of other issues. There are a number of different technologies in use and each one has its own particular strengths and weaknesses that will impact the manner in which it is used and the efficacy of the results it will return. Along with these individual modalities, the form of cancer that is being imaged will also affect the results that are obtained. Certain forms of cancer are simply easier to image than others. Mesothelioma, especially pleural mesothelioma, remains one of the more difficult cancers to image as it is primarily a diffuse disorder that affects tissue that surrounds large areas of the body.

Research is on-going regarding the most efficient use of the various imaging modalities for mesothelioma. A report has recently been released that assesses the strengths and weaknesses of current techniques and notes some future directions that may positively impact the imaging of mesothelioma.

Imaging Modalities

The two most common imaging techniques used for mesothelioma imaging are computed tomography (CT) scans and positron emission tomography (PET) scans. Magnetic Response Imaging (MRI) is also used but CT and PET, as well as variations common to both, are the major techniques that will be covered here.

Computed Tomography (CT) Scans

CT is the primary imaging technology used in the diagnosis and staging of mesothelioma. It can be used to scan the entire pleural surfaces and is effective at identifying areas of benign vs. malignant tissue, at charting overall tumor morphology and can be effective at identifying local tissue invasion. It is not, however, effective at identifying the malignant status of the lymph nodes, so other techniques need to be used to investigate nodal status.

Position Emission Tomography (PET) Scans

PET functions by tracking how the body uses glucose. Tumors consumer sugar at a different rate than the rest of the body does, so PET scans are used to identify areas where sugars are over-consumed. FDG (fluorodeoxyglucose) is the molecule most often used in PET scans to measure tumor activity. PET scans are effective at identifying distant areas of tumor growth, but they suffer from poor spatial resolution so they are not effective at determining invasion into local surfaces. They do, however, show promise in the measurement of overall tumor response.

PET/CT

Integrated PET/CT has proven to be a real advance on the individual modalities. Precise registration of the two scans allows a deeper look at the underlying anatomic and functional structures at work. PET/CT is especially good at detecting the extent of disease involvement and in detecting distant metastases. It can also be used to identify lymph node status in the mediastinum, which is an area of connective tissue in the central chest that contains the heart, esophagus, trachea, and thymus. As such, PET/CT is useful as a preoperative technique to evaluate mesothelioma patients who may be candidates for curative surgery, such as extrapleural pneumonectomy.

Molecular Bioprobes

Molecular bioprobes are a relatively new area of research, but they hold great promise for imaging mesothelioma, as well as other cancers. The idea behind these bioprobes is they attach an antibody to mesothelioma cells that allows for more precise imaging of the actual biochemical and physiological changes that are taking place in the body. While standard imaging modalities are only able to measure the actual structural changes that emerge from the underlying biology, molecular bioprobes should allow doctors to see what is happening on a deeper level.

Conclusion

Mesothelioma remains one of the most difficult of all cancers to manage. Its complex biology makes imaging especially difficult. There is not a single imaging method that can be used without compromise, so doctors and other scientists are actively engaged in research to create more efficient imaging modalities. The paper that was covered in this news post was an attempt to quantify the current status of imaging techniques used in the diagnosis and staging of pleural mesothelioma. While much more research needs to be done, there is hope that new methods will allow more effective treatment of patients with this difficult disease.

Labels: mesothelioma

posted by Belluck & Fox at 11:25 AM
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Strativa Pharmaceuticals Acquires Commercialization Rights to Onconase(R) from Alfacell Corporation

Source: CNNMoney.Com

Strativa Pharmaceuticals and Alfacell Corporation have announced that Strativa has acquired the commercialization rights for Alfacell’s mesothelioma drug Onconase. Strativa paid an initial charge of $5 million for the exclusive right to market Onconase in the United States and its territories and will pay up to $30 million for it if FDA approval is received. The agreement allows Alfacell to co-promote Onconase in the future, as well as to possibly receive future milestone payments.

Onconase is a first-in-class oncology agent developed from Alfacell’s proprietary ribonuclease (RNase) technology. Current clinical trials have shown that Onconase triggers apoptosis (“cell death”) in cancer cells while ignoring healthy cells. It is currently in Phase III development and is being targeted for the treatment of pleural mesothelioma.

To learn more about Onconose, please visit the Onconase website.

Labels: mesothelioma

posted by Belluck & Fox at 10:24 AM
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Endoscopic Ultrasound-Guided Fine Needle Aspiration is Useful for Nodal Staging in Patients with Pleural Mesothelioma

Monday, January 14, 2008

Source: Endoscopic ultrasound-guided fine needle aspiration is useful for nodal staging in patients with pleural mesothelioma
(Diagn Cytopathol. 2008 Jan;36(1):32-7)

Effective surgical management of mesothelioma requires the identification of the extent of actual tumor mass, as well as the identification of the malignant status of a patient’s lymph nodes. The former is important so the treating physician understands how much of an area has been affected, while the latter can be indicative of systemic malignancy and a worse prognosis. Researchers have developed many tests to identify these issues, but new methods are regularly being studied to increase the accuracy of the reports. Researchers from the Duke University Medical Center and the University of Alabama at Birmingham have recently released the results of their study on the effectiveness of endoscopic ultrasound-guided fine needle aspiration (EUG-FNA) to determine the nodal status of patients who are being treated for pleural mesothelioma.

Introduction to the Study

Nodal status is an important metric in the analysis of any cancer, but this is especially true for patients with pleural mesothelioma who may be eligible for radical surgery. Previous studies have shown that patients with mesothelioma involvement in the lymph nodes who undergo an extrapleural pneumonectomy (EPP) have a statistically poor outcome, and because of this, some institutions will not perform an EPP for patients with nodal involvement. Thus, developing tests to identify nodal status is an especially important area of current research.

Computed tomography (CT) scans and/or positron emission tomography (PET) scans are currently used for the initial evaluation of a patient’s lymph nodes. If the scan shows any enlarged lymph nodes, then a more invasive procedure will be used to take a tissue sample of the enlarged nodes. The authors of the study were the first group to investigate the effectiveness of endoscopic ultrasound-guided fine needle aspiration (EUG-FNA) in determining nodal status for patients with mesothelioma.

EUG-FNA is a type of surgical biopsy where a thin, hollow needle is inserted into a tissue area and a sample of the cells from that area are removed for analysis. After the cells have been removed, they will be analyzed for the existence of any malignancy. In this case, the cells are removed from selected lymph nodes and those cells are analyzed for the presence of any mesothelioma cells. This procedure allows the doctor to better stage a patient’s disease than if he did not—or was not able to—examine the patient’s actual lymph nodes. EUG-FNA has previously been shown to be useful in the evaluation of lymph node status for patients with small cell lung cancer and with non-small cell lung cancer.

To evaluate EUG-FNA’s efficacy for mesothelioma patients, the authors analyzed its use in six patients with confirmed pleural mesothelioma. On two patients, they biopsied two sites, so a total of eight sites were evaluated.

Conclusion

EUS-FNA detected lymph node involvement in 50% of the cases it was completed on, while mediastinoscopy, which is an alternative technique, didn’t identify any. There were two false negatives in the EUS-FNA test, but they were attributed to sampling errors and not to cytological errors. In those cases, the area that was sampled didn’t show any malignancy, but other nodes were in fact malignant.

The authors feel that a full-scale clinical trial should be commenced to fully study the efficacy of EUS-FNA. They feel it can be very effective in the staging of mesothelioma and suggest its further study may have important implications for the treatment of this difficult disease.

Labels: mesothelioma

posted by Belluck & Fox at 5:33 PM
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Utility of WT-1, p63, MOC31, Mesothelin, and Cytokeratin (K903 and CK5/6) Immunostains

Friday, January 11, 2008

Source: Utility of WT-1, p63, MOC31, Mesothelin, and Cytokeratin (K903 and CK5/6) Immunostains in Differentiating Adenocarcinoma, Squamous Cell Carcinoma, and(Diagn Cytopathol. 2008 Jan;36(1):20-5)

The first step in a diagnosis of cancer is the definitive conclusion of the presence of malignant tissue. However, this tissue may not identify the particular form of cancer at work, so further analysis is often necessary. One of the techniques used for this latter diagnosis is immunostaining, where a tissue sample is treated with a reactive dye that becomes activated when it binds to a marker indicative of a certain form of cancer. The binding process then “stains” the tissue—providing a visual indication of the marker’s presence and, therefore, a determination of the type of cancer at hand.

One of the most difficult differentials to make is between malignant mesothelioma and poorly differentiated forms of adenocarcinoma of the lung and squamous cell carcinoma of the lung. Morphology analysis of the fluid from an effusion is not able to differentiate between these cancers, so scientists are searching for protein markers that can differentiate between them. Researchers from the University of Michigan School of Medicine have recently released a study that identifies possible markers.

Introduction to the Study

The search for biomarkers for mesothelioma and other cancers is an especially active form of research. The need for accurate differential diagnoses has driven researchers to experiment with a number of substances as possible markers, such as calretinin, CEA, BerEP4, CD15 and cytokeratins, but many of these do not have the high specificity required for such important decision-making. Some recent studies have recently identified a few more substances as possible makers—WE-1, p63, MOC31 and mesothelin—and it is these agents that the authors of the present study looked at. They also looked at the ability of cytokeratin staining to differentiate between the cancers.

The authors studied 43 samples of malignant effusions. 10 were adenocarcinoma (ADC), 15 were squamous cell carcinoma (SCC) and 18 were malignant mesothelioma, mainly pleural mesothelioma. Immunostaining for each of the four markers identified above (WE-1, p63, MOC31 and mesothelin) was performed on each sample.

WT-1

The authors found that WT-1 was perfect for determining a malignant mesothelioma diagnosis, as it stained in 100% of the mesothelioma cases and none of the ADC or SCC cases. Calretinin had previously been identified as the best positive marker for differentiating mesothelioma, but the authors recommended further study and greater use of WT-1 because of their excellent results.

P63

Antibody-staining against P63 showed significant staining for SCC, a lower threshold for ADC and none for mesothelioma. The authors support using a combination of P63-negative status and WT-1-positive status to differentiate mesothelioma from both SCC and ADC.

MOC31

The authors conclude that MOC31 wasn’t an effective marker by itself. It stained for ADC 100% of the time, 67% of the time for SCC and 35% for mesothelioma, so it could not differentiate between the malignancies enough on its own. However, when used in a panel with other antibody staining, the authors felt it could be used to differentiate between ADC/SCC and mesothelioma.

Mesothelin

Mesothelin is a marker that is under active investigation, but there are conflicting results returned from different studies regarding its efficacy. Some studies have come back with a 100% success rating for determining a mesothelioma diagnosis, but the authors of this study expressed disappointment at the results they obtained when staining for it. Their figures returned the following results: 100% ADC and 60% SCC, but only a figure of 47% for mesothelioma. The authors do not recommend mesothelin because of these results.

Cytokeratin Staining

The results for K903 and CK5/6 showed that ADC and SCC can be differentiated using cytokeratin staining, but it is only recommended if mesothelioma has been conclusively ruled out before the investigation.

Conclusion

The identification of new markers in cancer diagnosis is an important advancement on our knowledge. Early identification allows the patient to receive earlier treatment, which can be greatly beneficial. With a malignancy such as malignant mesothelioma, which has generally resisted long term treatment, early diagnosis is essential to maximizing patient response.

Labels: LungCancer, mesothelioma

posted by Belluck & Fox at 3:35 PM
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Human Health Effects Associated with the Commercial Use of Grunerite Asbestos (Amosite): Patterson, NJ; Tyler, TX; Uxbridge, UK

Tuesday, January 8, 2008

Source: Ribak, J., Ribak, G., Human health effects associated with the commercial use of grunerite …, Regul.Toxicol. Pharmacol. (2007), doi:10.1016/j.yrtph.2007.10.002

Asbestos does not refer to a single type of mineral, but to a family of six individual minerals that share common structural properties. The most common form of asbestos used in commerce was chrysotile. It is known as serpentine asbestos because of its short, curly fibers. The other five types of asbestos—crocidolite, amosite, anthrophylite, tremolite, and actinolite—are known as amphibole fibers and are characterized by long, rigid, needle-like fibers. The amphibole fibers are considered the most carcinogenic of the asbestos family, but all fiber-types are dangerous and are documented causes of malignant mesothelioma and lung cancer.

Amosite, known officially as grunerite asbestos, was one of the major amphibole fibers used commercially. It is considered among the most dangerous of the amphiboles, although its mechanisms of actions are not fully understood. In fact, scientists are still identifying the precise physiological effects that asbestos exposure has on the human body. Researchers from the National Institute of Environmental and Occupational Health in Isreal have recently summarized the available literature on amosite in an effort to better understand its carcinogenic properties.

Epidemiological Studies

There have been three epidemiological studies on populations exposed to amosite in the workplace. The first study looked at a factory in Patterson, NJ. This factory closed in 1954 and then moved to Tyler, TX. The second study looked at the cohort of workers employed by the Tyler factory. The last study looked at amosite and chrysotile factory in Uxbridge, United Kingdom.

Patterson, NJ

Record indicate that the Patterson, NJ factory only used amosite asbestos, so it makes an excellent study on the health effects of amosite exposure. A total of 820 workers were employed at the facility between 1941 and 1954 (the year the factory closed). It was an older, mainly white workforce. Through 1989, when the last study on Patterson was completed, 740 of the 820 employers had died and of those, 17 had mesothelioma. Previous studies reported at least 111 deaths attributable to lung cancer and 31 from asbestosis, but the 1989 study that listed mesothelioma deaths at 17 did not report on these other diseases. There were 8 cases of pleural mesothelioma and 9 cases of peritoneal mesothelioma. The average latency period of the disease was 31 years for both, but the mean duration of employment was quite different: 25.6 months for pleural mesothelioma and 43.8 months for peritoneal mesothelioma. Interestingly, the pleural group survived, on average, 12 months after diagnosis, while the peritoneal group only averaged 8 months. This is notable because peritoneal mesothelioma often presents with a slightly better prognosis.

The concentration of asbestos in the air was never definitely measured in Patterson, although estimates exist that place the levels between 14–75 f/ml. As a point of reference, current US regulations regarding asbestos concentration demand a figure of less than .1 f/mL.

Tyler, TX

After the Patterson factory closed, it was moved to a location in Tyler, TX, where the same equipment was reinstalled and used again. The cohort of workers studied here was employed between 1954 and 1972, when the plant closed for good. Unlike the Patterson location, air quality was measured and the levels varied between 15.9 f/ML and 91.4 f/ML for different parts of the factory. To put the latter number into prospective, with concentrations that high, a worker who only spent six months in that part of the factory would have a cumulative lifetime exposure level of greater than 45 f/mL years, which is 11-times higher than the 4 f/mL years figure for someone who worked forty-years at the current legal levels.

For workers of the Tyler, TX facility, 6 were diagnosed with mesothelioma, 35 with lung cancer and only three with asbestosis.

Uxbridge, UK

The last of the studies focused on a factory in Uxbridge in the United Kingdom. The factory was operational between 1947 and 1979. Between 1947 and 1972 the factory processed both amosite and chrysotile. Starting in 1972, the factory processed amosite only. The air quality of the Uxbridge factory got better over time. Although no studies were completed in the 1950s, exposure levels were estimated at over 100 f/mL. In 1964, efforts were made to reduce the dust that workers were exposed to and by the late 1960s, air studies returned a value of 30 f/mL for asbestos concentration. This was reduced to 2 f/mL by the early 1970s.

A total of 4820 workers were studied here. There were 5 mesotheliomas, of which 4 were pleural and 1 was peritoneal. There were also 57 cases of lung cancer and 9 of asbestosis.

Conclusion

The preceding descriptions indicate the malignant potential of grunerite asbestos. While asbestos exposure is always potentially harmful, certain forms of the mineral, such as amosite, are certainly more harmful than others. The studies summarized in this article clearly show that asbestos is too dangerous a substance for anyone to use.

Labels: asbestos, mesothelioma

posted by Belluck & Fox at 5:08 PM
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The Origins of Public Concern with Taconite and Human Health: Reserve Mining and the Asbestos Case

Friday, January 4, 2008

Source: Berndt, M.E., Brice, W.C., The origins of public concern with taconite and human health: …, Regul.
Toxicol. Pharmacol. (2008), doi:10.1016/j.yrtph.2007.09.019

In the 1960s, Reserve Mining was one of the largest mining companies in the United States, responsible for 11% of the total US iron production and almost 25% of taconite pellet production in the State of Minnesota. Reserve Mining rose to this position through the development of an innovative production process that created easy-to-store and ship taconite pellets from unprocessed taconite ore. The development of these pellets created surplus mineral waste, called “tailings,” that was then deposited at the bottom of Lake Superior. The environmental effects of these tailings on Lake Superior and the health effects they had on people who used water from the Lake became a major issue and Reserve Mining was eventually sued in Federal Court.

The journal Regulatory Toxicology and Pharmacology has recently published an article on the litigation history of this case that discusses the issues that were involved and summarizes the various rulings handed down.

Introduction to the Story

At the beginning of the iron mining industry, high-grade hematite ore was found in abundance and could be extracted from the earth and directly shipped to processing mills. However, as the industry grew and the demand for ore increased, hematite ore became more and more scarce and the ore that was left was relatively low-grade taconite ore, which required intermediate processing—known as beneficiation—before it could be shipped to mills for production. The beneficiation process created surplus mineral waste, called tailings, which had to be disposed of.

Reserve Mining grew to the position it did because of the work of Dr. E.W. Davis, the director of the Mines Experiment Station at the University of Minnesota, who developed a production process that created taconite pellets, which were more efficient to ship and easier for mills to use. Reserve Mining received a permit to build a taconite processing plant on Lake Superior and quickly grew from there.

In the early 1960s, the environmental effects of Reserve’s use of Lake Superior became an issue. By the end of the decade, Reserve found itself in state court fighting new water regulations that it claimed would force it to shut down and then, in 1972, it was sued by the EPA in federal court for violation of federal and state water standards. During this time, the discovery of asbestos-like materials in both the water supply of those who used water from Luke Superior and the air around the taconite mines and processing plants created a sense that Reserve Mining was poisoning the health of thousands of citizens.

The Federal Cases

Reserve Mining lost badly in the first round of the federal case, as Judge Miles Lord ordered in 1974 that its processing plant had to immediately cease depositing the taconite tailings into Lake Superior, meaning the plant itself would have to close. This order, however, was stayed and the Appeals Court gave Reserve Mining time to develop an on-land processing system.

One of the major issues involved with the case had to do with the health effects of the taconite that was being processed. As the structure of the taconite that Reserve Mining processed appeared similar to amosite, many people were rightly concerned that it could have the same carcinogenic properties that asbestos had. However, as asbestos disease is a disease of latency they couldn’t make those determinations then. A number of other issues were raised about fiber length and exposure levels, but these, too, were left unanswered.

The case was eventually settled in 1982, with Reserve Mining agreeing to pay $2 million to Duluth, MN and its surrounding communities. In its settlement, Reserve Mining did not admit any wrongdoing.

Conclusion

The Reserve Mining case was notable for a number of reasons, but most directly because the rulings raised important questions about the role between science and industry. The authors of the article note that we are now in a time where many of these questions can be answered and they advocate a new look at this important case.

Labels: asbestos

posted by Belluck & Fox at 4:33 PM
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In Australia, Patients and Government at Odds Over Mesothelioma Treatment Costs

Thursday, January 3, 2008

Source: JNCI Journal of the National Cancer Institute 2007 99(23):1750-1752; doi:10.1093/jnci/djm257

In the United States, the chemotherapy standard of care for pleural mesothelioma is combination therapy using pemetrexed, marketed as Alimta^® by Eli Lilly, and cisplatin. The USFDA approved this treatment—the only one officially approved for mesothelioma in the U.S.—in 2004 due to the successful results of a number of clinical trials showing the combination provided better tumor response and additional survival time than other treatments. However, not all countries initially approved the use of pemetrexed and cisplatin for the treatment of mesothelioma.

In Australia, pemetrexed had been previously approved only for the treatment of non-small cell lung cancer. The Pharmaceutical Benefits Advisory Committee (PBAC), which is the authority that approves funding for the drugs that will be distributed through the nation’s national health care system, had twice rejected listing pemetrexed for mesothelioma treatment due to the high cost of the drug, which at 20,000–25,000 Australian dollars (US$18,383–22,979) was more expensive than other treatments. The PBAC was also concerned that the side effects associated with pemetrexed were too great for the benefits it offered and that the dosing regimen was too strong.

Similar reactions were seen in England and Canada as well. Both national health care systems at first rejected pemetrexed due to its high cost and the side effects associated with treatment. In July of 2007, the UK finally approved the use of pemetrexed. In Canada, the individual provinces have different rules, but pemetrexed or raltitrexed, a drug in the same class as pemetrexed, is now available through a number of means.

Back in Australia, patient groups, such as the Asbestos Diseases Foundation of Australia, have been fighting for approval of pemetrexed. The drug has been available in some parts of the country, but because it was not been offered as part of the national health care system, it was not available universally. The Asbestos Diseases Foundation estimates that 35%–50% of all mesothelioma patients do not have access to the drug.

Recently, however, the PBAC reversed positions and has now approved pemetrexed for mesothelioma treatment, much to the approval of the Asbestos Diseases Foundation and for mesothelioma patients all over the country. In fact, Australia has the highest incidence rate of mesothelioma in the world. At 32 cases per million, it’s incidence rate is nearly three times that of the United States and is expected to grow until 2017. The PBAC changed their positions after Eli Lilly presented data showing pemetrexed was well-tolerated in most patients, and because Eli Lilly reduced the price by 10% and offered the drug in a smaller 50mg dose as compared to the traditional dose of 100mg.

Labels: mesothelioma

posted by Belluck & Fox at 1:13 PM
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Reactivity of Integrin-linked Kinase in Human Mesothelial Cell Proliferation

Wednesday, January 2, 2008

Source: Reactivity of integrin-linked kinase in human mesothelial cell proliferation (Interact Cardiovasc Thorac Surg. 2007 Nov 29)

A number of cellular processes are necessary for the growth and the spread of cancer. The great successes in fighting cancer that we’ve seen in the past decade are a direct result of our growing knowledge of these aberrant developments. New research pathways continue to reveal themselves and researchers from every major country are actively pursing these new avenues. Researchers from Austria have recently released the results of their work studying the relationship between integrin-linked kinase (ILK) expression and malignant pleural mesothelioma. ILK has been found to be significantly overexpressed in a number of other cancers, so its expression in pleural mesothelioma may give doctors another tool in the diagnosis of this difficult disease.

Introduction to the Study

Integrin-linked kinase (ILK) is an essential protein involved in multiple cellular processes, including cell migration, cell proliferation and cell-adhesion, as well as in signal transduction. Functionally, it links integrins and growth factors to a number of signaling pathways. Whereas properly regulated ILK is known to regulate tumor angiogenesis, dysregulated ILK has been implicated in tumor growth and seems to impair apoptosis among affected cells. ILK is overexpressed in a number of different cancers, including “prostate, colon, gastric and ovarian cancers, malignant melanomas and…non-small cell lung cancer.” Immunohistochemical analysis (IHC) can be used to identify its expression in these cancers.

To study what, if any, relationship ILK has with mesothelioma incidence, researchers from Austria analyzed 34 tissue samples taken from people who underwent surgery for pleural mesothelioma between 1999 and 2006. They analyzed this tissue for ILK expression, as well as for epidermal growth factor receptor (EGFR) expression. EGFR is the surface receptor for epidermal growth factor protein ligands and mutations of it are a known co-factor in the development of cancer.

The demographics of the sample population were as follows: mean age of 68.1 years, with a mostly male population (30 vs. 4 females). As would be expected, epitheloid mesothelioma was the most common histological subtype of the tissue samples (19), with sarcomatoid mesothelioma the least common (2).

Conclusion

Using immunohistochemical analysis, 29 of the mesothelioma tissue samples tested positive for ILK, which is a percentage of 87.9. In these tissues, the actual tumor area stained at more than 50% coverage, while normal mesothelial tissue, as well as normal lung parenchyma, did not show any ILK expression at all. At 75.8% of cases, EGFR expression was seen in a plurality of the tissue samples as well, but not to the extent that ILK was seen.

The researchers note their work is the first to establish a correlation between ILK expression and mesothelioma and they conclude that ILK is an important biomarker in the diagnosis of the disease. With a diagnostic potential approaching 90%, the authors state that not only is ILK effective in identifying mesothelioma as such, it’s useful to differentiate it from other malignancies, such as lung adenocarcinoma where ILK expression is seen in less than 30% of cases. The authors also state that other studies have noted that ILK inhibition has been associated with improved apoptosis and inhibition of metastasis, so the identification of ILK expression in malignant pleural mesothelioma may also provide a future avenue of treatment for this disease.

Labels: mesothelioma

posted by Belluck & Fox at 2:48 PM
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