Bortezomib may help mesothelioma patients

May 30, 2007

Malignant pleural mesothelioma is resistant to chemotherapy. Bortezomib is an FDA-approved proteasome inhibitor that is currently being studied for its effects on various types of cancer, but has not been studied extensively in mesothelioma.In this report, the researchers determine the biological and molecular response of mesothelioma cells to bortezomib alone and in combination with cisplatin and with pemetrexed (Alimta).

The researchers used mesothelioma cell lines, a normal mesothelial cell line, and a lung cancer cell line in survival studies designed to test the effect of bortezomib on mesothelioma. They also tested bortezomib with cisplatin alone, and with pemetrexed alone. They also tested bortezomib by combining it with Alimta/cisplatin by administering it concurrently or by varying the order of administration.

They determined the effect of bortezomib on: the cell’s life cycle cycle, apoptosis (cell death), on the expression of cell cycle proteins p21/WAF1 and p27/KIP1, and on apoptosis-related proteins IAP-1, IAP-2, survivin, and XIAP. These proteins are important for cells, and if they can be affected in the proper way, the cancer cells will die.

Bortezomib was highly cytotoxic to mesothelioma cells and induced cell cycle arrest. Apoptosis increased in a in 3 of 4 mesothelioma cell lines. Bortezomib stabilized or increased protein levels of p21/WAF1 and IAP-1 and to a lesser degree p27/KIP1, IAP-2, XIAP, and survivin.

In combination studies with cisplatin, bortezomib at high concentrations worked well to kill cancer cells, and did not work well with cisplatin at low concentrations. Bortezomib increased the toxicity of cisplatin and pemetrexed in a concentration-dependent manner when administered prior to either. Bortezomib may improve outcome in pleural mesothelioma patients alone or in combination with standard chemotherapy, but the order of administration is likely to be important. This study justifies further evaluation of bortezomib in MPM.

From: Cancer Chemother Pharmacol. 2007 May 24

Preclinical studies of the proteasome inhibitor bortezomib in malignant pleural mesothelioma.

Gordon GJ, Mani M, Maulik G, Mukhopadhyay L, Yeap BY, Kindler HL, Salgia R, Sugarbaker DJ, Bueno R.

The Thoracic Surgery Oncology Laboratory and the Division of Thoracic Surgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St., Boston, MA, 02115, USA, ggordon@partners.org.


Potential Alimta side effect in mesothelioma patients: severe cutaneous toxicity

May 30, 2007

Alimta is a chemotherapeutic drug used as first line treatment for malignant pleural mesothelioma in association with Cisplatin, and alone as second line treatment in resistant or relapsing non-small cell lung cancer (NSCLC). However, cutaneous toxicity has been described, principally as a rash. Cutaneous toxicity of all grades has been observed in up to 14%, and grade 3 or 4 toxicity in 0.8-1.3% of cases.

This is a case report of an 85 year-old man treated for NSCLC 15 days after administration of the second cycle of Alimta. The patient had cutaneous lesions including erythema, bullae, and desquamation, associated with deterioration in his general condition; a skin reaction corresponding to Lyell’s syndrome. Treatment with steroids and gammaglobulins led to local resolution and improvement in his general condition.

CONCLUSION: Cutaneous toxicity from Alimta should be recognised on account of its potential severity. The appearance of skin lesions is an indication for careful follow-up for evidence of Lyell’s syndrome for which intensive management is needed.

Article in French by: Tummino C, Barlesi F, Tchouhadjian C, Tasei AM, Gaudy-Marqueste C, Richard MA, Astoul P.

Faculté de Médecine, Université de la Méditerranée-Assistance Publique Hôpitaux de Marseille, Service d’Oncologie Thoracique, Hôpital Sainte-Marguerite, Marseille, France.

 


Criticism increases of EPA advisory panel’s pro-asbestos, anti-mesothelioma victim slant increases

May 24, 2007

Thursday, 24 May 2007, 03:02 CDT

Asbestos Board in Question: Concerns Raised About Candidates

By Susanne Rust, Milwaukee Journal Sentinel

May 24–Potential panelists for a federal asbestos advisory board have financial conflicts that could pose a threat to public health and safety, according to researchers and environmental groups.

They are concerned about an Environmental Protection Agency board being convened to draft a risk assessment for asbestos fibers. Public comments concerning the panel will close today.

Although the EPA does not regulate asbestos, the agency provides a risk assessment that state and other federal agencies use to define exposure safety. These assessments are used as guides in the cleanup of asbestos-contaminated sites, including Superfund sites.

According to Jennifer Sass of the Natural Resources Defense Council, the recommendations of this panel are “likely to impact federal clean-up standards and may have further impacts on occupational and public health protections in the U.S. and internationally.”

The council and others are particularly concerned with “short list” nominees who have represented corporations such as W.R. Grace & Co. — a company that owned a vermiculite mine in Libby, Mont. The mine was closed in 1990 after reports of asbestos-related illness and death in the town.

The short list of 65 people also includes scientists who either own or work for product defense consulting firms. These are companies hired by corporations and trade associations to influence policy. The defense council is concerned about 12 of the nominees.

“The finances of these scientists are so closely linked to companies affected by federal asbestos policy that they should not be included on a panel whose work will help shape such policy,” wrote David Michaels in a letter to the EPA. He’s is a professor of environmental and occupational health at George Washington University.

The EPA panel is charged with reviewing a new risk assessment model, designed by the agency’s Office of Solid Waste and Emergency Response, which would allow the office to develop site-specific cancer assessments for Superfund sites.

The panel will have no policy or regulatory role. Its advice will be used to inform regulation, not set it, said Tony Maciorowski, deputy director of the EPA’s scientific advisory board office.

Asbestos is a known human carcinogen. Its inhalation has been linked to lung cancer and mesothelioma, a cancer that infects the lining of the lungs and other organs.

According to an internal EPA newsletter, the new model will help determine the carcinogenic potential of asbestos at specific sites and could result in cancer risk assessments that differ from the EPA’s current default.

Watchdog groups are wary about nominees who have argued on behalf of asbestos trade associations for other federal agencies, including the National Institute for Occupational Safety and Health.

On May 4, three of the nominees — Ernest McConnell, president of ToxPath Inc.; Graham Gibbs, president of Safety Health Environment International Consultants; and Wayne Berman, president of Aeolus Inc. — appeared at an Occupational Safety and Health agency meeting to discuss asbestos research. The three nominees advocated on behalf of the National Stone, Sand & Gravel Association, a trade group affected by federal asbestos regulations.

McConnell, who has researched asbestos for federal agencies and industry, said the panel should consist of people who know the most about the issue, regardless of their funding source.

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Copyright (c) 2007, Milwaukee Journal Sentinel


Former EPA chief to testify to Congress on fraudulent 9/11 air quality bulletins impacting asbestos, mesothelioma

May 21, 2007

Here’s the link to the story in the Washington Post.


Government policy will increase asbestos, mesothelioma cancers

May 21, 2007

Asbestos, Minerals, and United States Policy
by Bill Robbins

An April 19, 2007 decision by the U.S. Court of Appeals (Lombardi v. Whitman) provides stunning insight into the aftermath of the 9/11 attack. Five years after rushing to assist Twin Tower victims, first responders and cleanup workers are dying. The injured participated in search, rescue, and clean-up work at the site with no equipment to protect their lungs. In court documents, the plaintiffs alleged the U.S. Government issued reassuring and knowingly deceptive and misleading statements that the ambient air they inhaled presented no health risks to the public.

The Inspector General of the Environmental Protection Agency (EPA) reported unsafe air continuously detected for weeks after the attack on the Twin Towers. Yet, the White House Council on Environmental Quality routinely edited that information from EPA press releases.

The court’s ruling against the workers affirmed the government’s right to lie, mislead, and omit information in order to insure immediate search, recovery, and clean-up. Moreover, the court claimed the government had a responsibility to create the impression it was safe for people to reside and work in areas near Ground Zero, so they would return to their normal routines. The Court declared that everyone knew, “That one essential government function, in the wake of disaster, is to put the affected community [and nation] on a normal footing.” Preserving the economy (reopening the New York Stock Exchange), restoring services, and avoiding panic were higher priorities than individual or family health.

The extent of human casualties continues to evolve. The administration’s decision to issue false air quality announcements will end more American lives than the terrorists’ attack. Twenty-one thousand workers, and their families, are now suffering from inhaling the building ‘dust.’ Their medical treatment costs are projected to exceed $400 million annually.

New York City rescue workers requested information by way of the Internet, including such questions as “What are the health effects of inhaling this dust from pulverized building materials?” Posted replies alerted the workers to immediately don respirators. The replies described mineral exposure symptoms, and suggested that exposed personnel seek medical treatment and file worker compensation claims. These postings conflicted with government policy and were quickly deleted.

Today, survivors avoid Lower Manhattan. In addition, over 670,000 New Yorkers are still at risk to environmental illnesses.

Minerals indiscriminately kill. Mineral dust, often released during building renovation, takes more lives each day than all the nine-millimeter handguns do in a year. The World Health Organization claims 54% of all worker deaths that result from exposure to workplace carcinogens originated from one mineral source  asbestos. Asbestos is a generic name for six distinct minerals. Over 4,000 industrial applications of these minerals exist, and when inhaled, they are all injurious to your health.

Globally, people who live or work in buildings whose windows do not open and whose entry points are constructed with doorway airlocks are under similar attack. Sealed buildings are seen as a way to reduce energy use and cut operating expense. But, in a sealed building air forced through the ventilation system collects and spreads mineral dust throughout the building. Sick building syndrome and respiratory problems are the fate of those who live or work in such structures. Initial diagnoses often advance into debilitating, life-ending illnesses.

The 9/11 attack and the administration’s appalling response provide an unfortunate observation. Tower responders worked outside, gradually wind and rain dissipated the Ground Zero toxins. Still, one third of the workers have already developed progressive illnesses.

Andrew Robbins is the author of It Took My Breath Away: One Man’s Experience May Save Your Life.


California Superior Court upholds loss of consortium for mesothelioma victim

May 18, 2007

A recent California appellate decision (Jonnie Lee Pounds v. Crane Co., May 2007) upheld the loss of consortium claim for the wife of a mesothelioma victim poisoned by asbestos. The corporate defendant, Crane Company, argued that since the victim’s exposure to their product ended in 1959, and since the victim and his wife didn’t get married until 1985, the wife couldn’t claim loss of consortium. This specious argument tried to unfairly apply settled law–that loss of consortium claims must be based on a marriage that existed at the time the claim arose–to the unique situation of mesothelioma patients in order to avoid paying legitimate damages.

The reason for the traditional law is that negligent acts and the ensuing injury are almost always closely contemporaneous. If a victim is injured before marriage, his spouse cannot claim that the pre-marital injury deprived her of marital consortium, as both were unmarried and were aware or should have been aware of the injury. The key is that the negligence and the injury happen close together.

The obvious injustice in applying this reasonable law to mesothelioma victims is that the negligent act (being forcibly exposed to asbestos) can be separated from the actual manifestation of injury by as much as 70 years due to the long latency period associated with mesothelioma. Neither husband nor wife will have any inkling that an injury has taken place. In the context of mesothelioma it is extremely difficult to say when the injury occurs. Citing a previous case, the court said that mesothelioma “is a latent, progressively developing disease–decades can often pass between the time a person i sfirst exposed to asbestos and the time he first develops a cancerous mesothelioma tumor. Moreover, although early formation of undetected cellular changes ultimately leads to contraction of the disease, it may be years before the cancerous cells will result in a tumor large enough to be detected, be medically diagnosed, or cause symptomatology of the disease…No temporally discrete event exists that encompasses the defendant’s breach and the plaintiff’s injury.” Buttram v. Owens-Corning Fiberglass Corp. (1997) 16 Cal. 4th 520, 529.

The court concluded that because of the time gap between negligent act and actual injury, the victim’s wife could claim loss of consortium.


MedScape review of peritoneal mesothelioma

May 18, 2007

Follow this link, and sign up for a free account to register. This is a very good overview of peritoneal mesothelioma, including the disease’s background, its epidemiology, a clinical picture of peritoneal mesothelioma, its diagnosis, pathology, treatment, outcome/prognosis, a conclusion section, with a table and references.