Karmanos Researchers Identify Pathway for Treatment of Malignant Pleural Mesothelioma

DETROIT, April 17,2007 /PRNewswire/ -- The Barbara Ann Karmanos Cancer Institute today announced significant scientific findings that could lead to better treatment and therapies for cancer patients suffering from malignant pleural mesothelioma.

Karmanos scientists presented their research at the American Association of Cancer Research (AACR) annual meeting in Los Angeles, CA.

"We are getting closer and closer to making an impact on this insidious disease," said Anil Wali, Ph.D., an associate professor with Karmanos who led a group of cross-collaborative researchers in studying the ubiquitin-proteasome proteolytic (UPP) pathway regulatory proteins.

Their study demonstrated that protein ubiquitination and degradation are critical players in the spread of mesothelioma. After studying 241 genes involved in the UPP pathway, Wali's group determined 33 genes were differentially expressed among epithelioid and biphasic histotypes.

"We have already reported earlier detection biomarkers that can be utilized in assessing the high risk groups of patients," Dr. Wali said. "Now, if we can develop a therapy to target this pathway, we will be one step closer to halting this disease."

Malignant pleural mesothelioma is an aggressive, asbestos-related thoracic cancer affecting about 3,000 new patients in the United States annually. Despite advances in cancer treatment, the average survival rate remains low and the majority of patients die within two years of diagnosis. Currently there is no cure.

The Karmanos Cancer Institute has a long history of mesothelioma education and treatment. In 2004, the Institute joined with Wayne State University's Center for Occupational and Environmental Medicine to create the National Center for Vermiculite and Asbestos Related Cancers.

It addresses the need for early diagnosis and aggressive treatment for those afflicted with asbestos-related diseases. John C. Ruckdeschel, M.D., president and chief executive officer of KCI, co-directs the center in conjunction with Michael R. Harbut, M.D., M.P.H., F.C.C.P., an expert in the diagnosis and treatment of environmental and workplace diseases. Dr. Ruckdeschel, an internationally recognized figure in both lung cancer research and treatment, contributed to the research and authorship of today's presentation.

SOURCE: Fujirebio Diagnostics, Inc., March 10, 2007

NYU Study Validates Use Of Fujirebio Diagnostics' MESOMARK Test For Monitoring An Asbestos-Linked Cancer

Malvern, PA - There is new hope for the thousands of Americans suffering from mesothelioma, an aggressive form of cancer linked to asbestos exposure. Results from a recent study conducted by researchers at New York University (NYU) School of Medicine show the MESOMARK Assay, the world’s first and only in vitro test for monitoring mesothelioma developed by Fujirebio Diagnostics, Inc., is an effective way to measure proteins within the blood that reflect changes in disease. The findings represent a major milestone in the management of mesothelioma, as the test may enable doctors to more accurately monitor patients for treatment.

Mesothelioma causes fluid to accumulate in the sac lining of the chest, the abdominal cavity or the area around the chest. Primarily caused by work-related asbestos exposure, physicians have long suspected it could be identified by the presence of soluble mesothelin-related proteins (SMRP) that are released into the blood stream by diseased cells. Previously, these proteins have been difficult to detect, and patient monitoring required a comprehensive series of diagnostic tests. Even the most advanced tests available are of limited utility in evaluating changes in tumor volume, a key factor for monitoring patient status and response to therapies.

In the study led by Dr. Harvey Pass, Department of Cardiothoracic Surgery, NYU School of Medicine, researchers used the MESOMARK Assay to test serum and pleural effusions of diagnosed malignant mesothelioma patients. Results from the study, presented recently at the Society of Thoracic Surgeons Annual Meeting in San Diego, revealed that these patients had statistically significantly higher amounts of SMRP than those in the control group which included individuals with well documented asbestos exposure, as well as patients with other cancers. Additionally, SMRP levels were found to rise among diagnosed patients as the disease progressed to more advanced stages.

“As a relatively rare and often misdiagnosed disease, mesothelioma has been somewhat of a mystery to the medical world,” said Dr. Harvey Pass. “For years, we’ve believed SMRP played a role in the classification of the disease, but there was no accurate way to confirm it. Our findings not only show that SMRP is indeed a valid biomarker for mesothelioma, but also justify further research as a prospective screening test. As we continue to learn more about this complex disease through tests such as Fujirebio Diagnostics’ MESOMARK Assay, we might finally be on our way towards improving survival rates and the quality of life for patients diagnosed with this aggressive and often fatal disease.”

“Mesothelioma can take as long as 75 years to develop after exposure to asbestos, yet once it does, it rapidly grabs hold of a person’s body. In fact, there is only about a 10 percent survival rate for patients after three years following diagnosis,” said Dr. W. Jeffrey Allard, vice president and chief scientific officer of Fujirebio Diagnostics. “The MESOMARK test may give physicians a way to determine how rapidly the disease is progressing and if they’re administering the appropriate treatment regimen. In the future, our hope is that it could one day lead to detection of mesothelioma at an early and potentially curable stage.”

Mesothelioma is often difficult to diagnose, as many of its symptoms are similar to numerous other conditions, including various forms of cancer. Currently, more than 100 million people worldwide have been exposed to asbestos through their professions over the years – often unknowingly – including shipyard workers, insulators, boilermakers, plumbers and maintenance workers. It is estimated that 10,000 new cases are diagnosed each year worldwide.

Approved by the U.S. Food & Drug Administration (FDA) under the Humanitarian Device Exemption (HDE) program on January 24, 2007, the MESOMARK Assay test kit was developed by Fujirebio Diagnostics to measure levels of SMRP in serum of patients diagnosed with biphasic or epithelioid mesothelioma. Via a simple blood test, it may be used to monitor patients confirmed as having the disease, for recurrence in patients following surgery, or for measuring response to therapies.

Source: Alfacell Corporation, January 30, 2007

Alfacell Corporation Granted U.S. Orphan Drug Designation for ONCONASE® for Treatment of Malignant Mesothelioma

First-in-Class RNAi Drug in Phase IIIB Confirmatory Trial for Unresectable Malignant Mesothelioma

BLOOMFIELD, N.J., Jan. 30 /PRNewswire-FirstCall/ -- Alfacell Corporation, a biopharmaceutical company focused on the discovery, development and commercialization of novel ribonuclease therapeutics for cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation in the United States for the company's lead drug candidate, ONCONASE® (ranpirnase), for treatment of malignant mesothelioma. Alfacell is evaluating ONCONASE in a confirmatory Phase IIIb clinical trial in unresectable malignant mesothelioma (UMM).

Orphan drug designation permits Alfacell to be awarded seven years of marketing exclusivity for ONCONASE for the malignant mesothelioma indication upon FDA approval for this indication. Other benefits for which Alfacell is eligible with the orphan drug designation include protocol assistance by the FDA in the preparation of a dossier that will meet regulatory requirements, tax credits, research and development grant funding, and reduced filing fees for the marketing application.

"Orphan-drug designation in the United States is an important milestone for everyone associated with Alfacell, including malignant mesothelioma patients, investors and employees," said Kuslima Shogen, the company's chairman and chief executive officer. "This designation represents recognition of the potential of our lead drug candidate by the FDA, in addition to the previously granted fast-track development status in the United States, as well as the orphan-drug designations received in Europe and Australia for malignant mesothelioma. Moreover, it's a significant event for us in what is a transformational year for our company."

The FDA orphan drug designation provides incentives to pharmaceutical and biotechnology companies to develop drugs for the treatment of diseases affecting fewer than 200,000 people in the United States. Malignant mesothelioma qualifies under this requirement because approximately 4,000 to 5,000 new cases are reported in the United States each year.

About ONCONASE®

ONCONASE is a first-in-class therapeutic from Alfacell's proprietary ribonuclease (RNase) technology platform. ONCONASE has been shown in vitro and in vivo to target tumor cells while sparing normal cells. ONCONASE is internalized by endocytosis and released into the cytosol of the cancerous cell, where it selectively degrades tRNA beyond repair. In doing so, ONCONASE inhibits protein synthesis, stops cell cycle proliferation, and induces apoptosis (programmed cell death).

In addition to the ongoing confirmatory Phase IIIb registration study in malignant mesothelioma, the company is conducting an ONCONASE Phase I/II trial in Non-Small Cell Lung Cancer (NSCLC) and other solid tumors.

FDA Approves MESOMARK® Assay for the Management of Mesothelioma Patients

Source: Fujirebio Diagnostics, Inc, January 25, 2007

Fujirebio Diagnostics Receives FDA Approval for the MESOMARK® Assay for the Management of Mesothelioma Patients

MALVERN, Penn.--(BUSINESS WIRE)--Fujirebio Diagnostics, Inc. (FDI) received approval from the Food & Drug Administration (FDA) under the Humanitarian Device Exemption (HDE) program for the MESOMARK® Assay, the world's first in-vitro test for mesothelioma, a form of cancer linked to asbestos exposure. Via a simple blood test, the MESOMARK test enables doctors to monitor patients diagnosed with biphasic or epithelioid mesothelioma.

"The MESOMARK test signifies the beginning of a new era in monitoring mesothelioma malignancies," said Dr. W. Jeffrey Allard, vice president and chief scientific officer of Fujirebio Diagnostics. "As the first in-vitro test for patients with this aggressive disease, it will enable doctors to more accurately detect recurrence and monitor treatment of patients."

The MESOMARK Assay test kit was developed to measure levels of a biomarker, mesothelin, in serum. Biomarkers are substances found in higher-than-normal concentrations in the blood, urine or body tissues of patients with certain types of cancers. The test may be used to monitor patients confirmed as having mesothelioma, for recurrence in patients following surgery, or for measuring response to therapies. The test will be available nationally to physicians, via a central reference lab, in the first quarter of 2007.

"Current diagnostic tests are less than ideal for quantification of changes in tumor volume, which is key to managing the disease," continued Allard. "As the MESOMARK results correlate with tumor volume*, it provides a much needed tool for monitoring patient status. It is our plan to collect additional data in the future to support the use of the test to detect mesothelioma."

"Development of a reliable biomarker is a major advance in the care of mesothelioma," said Chris Hahn, executive director of the Mesothelioma Applied Research Foundation (Meso Foundation). "Fujirebio Diagnostics and the MESOMARK test are now making it possible - with a simple blood test -to monitor response to treatment and to detect recurrence following treatment. This provides an important head start to patients racing against this aggressive cancer." The Meso Foundation is the national research funding, patient support and advocacy organization dedicated to eradicating mesothelioma as a life-threatening disease.

Mesothelioma affects the sac lining the chest, the abdominal cavity or the area around the heart. Many people with this cancer have been employed in environments where they inhaled asbestos, such as in the shipbuilding and construction industries. Most insulation and construction materials manufactured before the mid-1970s contained asbestos, including insulation on pipes and boilers; fireproofing spray; roof, floor, and ceiling tiles; and brakes and clutches. Others have been exposed to asbestos in households or the general environment. Currently, more than 100 million people worldwide have been exposed to asbestos through their professions over the years - often unknowingly - including shipyard workers, insulators, boilermakers, plumbers and maintenance workers.

Progress on Clinical Development Program for ONCONASE(R) in Malignant Mesothelioma

BLOOMFIELD, N.J., Aug. 31, 2006/PRNewswire-FirstCall/ -- Alfacell Corporation announced today an update regarding the ongoing randomized, multi-center, multi-national, confirmatory Phase IIIb registration study for its lead anti-cancer drug, ONCONASE(R) (ranpirnase). This pivotal trial is evaluating the effectiveness of ONCONASE plus doxorubicin in improving the survival of patients with unresectable malignant mesothelioma (UMM) over doxorubicin alone.

The Company's Chief Executive Officer and Chairman of the Board of Directors, Kuslima Shogen, commented, "As a result of our recently completed financing we are in a strong position to further accelerate our clinical and regulatory strategy for ONCONASE. To date, we have accrued more than 360 patients, and are awaiting the 316 events required to trigger the final analysis. We look forward to completing the study and to adhering closely to our desired critical path, which centers on positive results from the final analysis leading to the filing of an NDA."

Shogen stated, "ONCONASE has previously been granted Fast Track status by the FDA for UMM, which allows us the opportunity to submit sections of an NDA as they are prepared. As such, we are continuing to finalize components of the Chemistry Manufacturing and Controls (CMC) section, which we plan to submit by end of third quarter 2006."

Shogen concluded, "Overall, we are pleased with the consistent progress the Company has made in the ONCONASE UMM clinical program, and that we remain on track with our previously stated timelines. We look forward to providing future updates on our progress toward marketing approval, as well as ongoing and new ONCONASE trials in major cancers."

New Research Shows Unique Promise of Onconase in the Prevention and Treatment of Mesothelioma

Press Release from Alfacell Corporation

New Research Findings Published in National Academy of Sciences Journal Show Unique Promise of ONCONASE in the Prevention and Treatment of Mesothelioma and Lung Cancer Caused by Asbestos

June 27, 2006

BLOOMFIELD, N.J., /PRNewswire-FirstCall/ -- Alfacell Corporation announced today that groundbreaking, independent new research findings show that the elusive molecular mechanism that asbestos uses to provoke lung cancer may have been identified. The research also found that ONCONASE® (ranpirnase) may be one of the most effective methods of treatment for mesothelioma and lung cancer caused by this mechanism, and may even reduce the incidence of these cancers in those exposed to asbestos.
These findings were included in the article, 'TNF-Alpha inhibits asbestos induced cytotoxicity via a NF-KappaB dependent pathway, a possible mechanism for asbestos induced oncogenesis,' published in the June 23rd issue of Proceedings of the National Academy of Sciences (PNAS), the official journal of the U.S. National Academy of Sciences. Michele Carbone, M.D., Ph.D., authored the article with Dr. Haining Yang from the Thoracic Oncology Program, Cardinal Bernardin Cancer Center, Loyola University, Chicago, and 10 other leading U.S. cancer researchers. Dr. Carbone is Professor and Director, Thoracic Oncology Cancer Center, University of Hawaii, and serves as Chairman of Alfacell's Thoracic Cancer Advisory Board.

Dr. Carbone and his colleagues found that asbestos triggers the release of TNF-Alpha (Tumor Necrosis Factor-Alpha), a pro-inflammatory cytokine critical to the functioning of both innate and adaptive immune responses. The release of TNF-Alpha sets in motion a biochemical chain of events that led to the protection of asbestos-damaged cells from death. The cells exposed to asbestos were found to have produced TNF-Alpha. This caused the activation of the NF-KappaB (Nuclear Factor-Kappa B) protein, a transcription factor, found in all cell types, that plays a critical role in regulating immune response. Ineffective regulation of NF-KappaB has been linked to cancer and other diseases. The activation of NF-KappaB protected asbestos-damaged cells against cell death. Because the damaged cells did not die, they could then go on to develop into a cancer.

The authors state that because of this novel understanding of the molecules and mechanisms involved in asbestos toxicity, new methods of prevention and treatment could be developed that specifically target the inflammatory pathway activated by TNF-Alpha and its target NF-KappaB. ONCONASE was one of only two drugs cited in the article as targeting these pathways. As such, the researchers concluded that ONCONASE holds promise to reduce the incidence of mesothelioma and lung cancer in asbestos-exposed cohorts (groups of patients).

"ONCONASE inhibits the same pathways that we have shown lead to mesothelial cell malignant transformation and mesothelioma. Therefore, we hope to test the possible efficacy of this drug to prevent mesothelioma in high risk cohorts. The minimal side effects of ONCONASE make this approach feasible," stated Dr. Carbone.

Zbigniew Darzynkiewicz, M.D., Ph.D., Director of the Brander Cancer Research Institute, New York Medical College and a member of Alfacell's Scientific Advisory Board, stated, "The mechanism by which ONCONASE produces these effects appears to involve suppression of induction of the survival genes triggered by anti-tumor agents in cancer cells. Indeed, in preclinical studies, ONCONASE was found to amplify the efficacy of several chemotherapy drugs."

Dr. Darzynkiewicz added, "Many other types of cancer utilize the same pathway as mesothelioma. As such, it is reasonable to expect that ONCONASE will have wide clinical application as an anti-cancer agent, with particular promise as an adjunct in chemotherapy or in radiotherapy in treatment regimens for many different tumor types."

"Eight years ago, we hypothesized on the role of TNF-Alpha and NF-KappaB in ONCONASE's mechanism of action (Deptala et al, International Journal of Oncology, July 1998; Potentiation of tumor necrosis factor induced apoptosis by ONCONASE)," Dr. Darzynkiewicz concluded. "It is exciting to see strong affirmation of that hypothesis today."

New diagnostic tool for mesothelioma to be developed

Source: Rosette Genomic, April 23, 2007

NYU Medical Center Partners With Rosetta Genomics to Develop a Line of Diagnostic Tools for Lung and Mesothelioma Cancers

REHOVOT, Israel and NEW YORK, New York, April 23 /PRNewswire-FirstCall/ -- Rosetta Genomics, Ltd. announced today that it has partnered with NYU Medical Center with the aim of developing a line of early detection diagnostic products for lung, and Mesothelioma cancers.

The early detection test will mainly target over 45 million Americans who are at an increased risk of lung cancer due to smoking, as well as those who have been exposed to asbestos fibers. The test will utilize Rosetta Genomics' proprietary protocol to extract microRNAs from a simple blood draw.

"A test that will be able to detect cancer at an early stage using a simple blood draw will have far reaching implications on the fight against cancer," noted Dr. Harvey Pass, Professor and Chief, Division of Thoracic Surgery and Thoracic Oncology at NYU Medical Center. "MicroRNAs have been shown to hold great potential as effective biomarkers for various cancers, and I believe that NYU Medical Center's vast experience with lung cancer and Mesothelioma, coupled with Rosetta Genomics' expertise in the microRNA field, will allow us to successfully advance this much needed test forward."

Mesothelioma Signs and symptoms

Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space are often symptoms of pleural mesothelioma.

Symptoms of peritoneal mesothelioma include weight loss and cachexia, abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.

These symptoms may be caused by mesothelioma or by other, less serious conditions.

Mesothelioma that affects the pleura can cause these signs and symptoms:

• chest wall pain
• pleural effusion, or fluid surrounding the lung
• shortness of breath
• fatigue or anemia
• wheezing, hoarseness, or cough
• blood in the sputum (fluid) coughed up

In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread, to other parts of the body.

Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:

• abdominal pain
• ascites, or an abnormal buildup of fluid in the abdomen
• a mass in the abdomen
• problems with bowel function
• weight loss

In severe cases of the disease, the following signs and symptoms may be present:

• blood clots in the veins, which may cause thrombophlebitis
• disseminated intravascular coagulation, a disorder causing severe bleeding in many body organs
• jaundice, or yellowing of the eyes and skin
• low blood sugar level
• pleural effusion
• pulmonary emboli, or blood clots in the arteries of the lungs
• severe ascites

A mesothelioma does not usually spread to the bone, brain, or adrenal glands. Pleural tumors are usually found only on one side of the lungs.

MESOTHELIOMA SYMPTOMS

The early symptoms of mesothelioma are generally non-specific, and may lead to a delay in diagnosis. Sometimes resembling viral pneumonia, pleural mesothelioma patients may present with shortness of breath, chest pain and/or persistent cough; some patients show no symptoms at all. A chest x-ray may show a build-up of fluid or pleural effusion (discussed below). The right lung is affected 60% of the time, with involvement of both lungs being seen in approximately 5% of patients at the time of diagnosis. Less common symptoms of pleural mesothelioma include fever, night sweats and weight loss. Symptoms of peritoneal mesothelioma may include pain or swelling in the abdomen due to a build-up of fluid, nausea, weight loss, bowel obstruction, anemia or swelling of the feet.

PLEASE KEEP IN MIND THAT THESE SYMPTOMS MAY BE CAUSED BY MESOTHELIOMA OR BY OTHER LESS SERIOUS CONDITIONS. ONLY A DOCTOR CAN MAKE A DEFINITIVE DIAGNOSIS.

Pleural Effusion

One of the most common symptoms of mesothelioma is a pleural effusion, or an accumulation of fluid between the parietal pleura (the pleura covering the chest wall and diaphragm) and the visceral pleura (the pleura covering the lungs). Both of these membranes are covered with mesothelial cells which, under normal conditions, produce a small amount of fluid that acts as a lubricant between the chest wall and the lung. Any excess fluid is absorbed by blood and lymph vessels maintaining a balance. When too much fluid forms, the result is an effusion.

Types

Pleural effusion is broken down into two categories, transudates and exudates. A transudate is a clear fluid that forms not because the pleural surfaces are diseased, but because of an imbalance between the normal production and removal of the fluid. The most common cause of transudative fluid is congestive heart failure. An exudate, which is often cloudy and contains many cells and proteins, results from disease of the pleura itself, and is common to mesothelioma. To determine whether a fluid is a transudate or exudate, a diagnostic thoracentesis, in which a needle or catheter is used to obtain a fluid sample, may be conducted.

Symptoms

As the volume of fluid increases, shortness of breath, known as "dyspnea", and sometimes pain, ranging from mild to stabbing, may occur. Some patients may experience a dry cough. When the doctor listens to the patient’s chest with a stethoscope, normal breath sounds are muted, and tapping on the chest will reveal dull rather than hollow sounds.

Diagnosis

Diagnosis of pleural effusion is usually accomplished with a simple chest x-ray, although CT scans or ultrasound may also be used. A special x-ray technique, called a lateral decubitus film, may be used to detect smaller effusions or to enable the physician to estimate of the amount of fluid present. If the underlying cause of the effusion is readily apparent (such as in the case of severe congestive heart failure), sampling of the fluid may not be necessary, however, because pleural effusion may be symptomatic of a number of disease processes from benign to malignant, a fluid sample is generally taken. Diagnostic thoracentesis, in which cells are extracted from the pleural cavity, is commonly done when the possibility of mesothelioma exists, however, in up to 85% of cases, the fluid tests negative or inconclusive even though cancer is present. It is ultimately a needle biopsy of the pleura (lining of the lung) or an open surgical biopsy which confirms a mesothelioma diagnosis.

Treatment

Pleural effusion caused by heart failure or infection can usually be resolved by directing treatment at the cause, however, when testing has realized no diagnosis, and fluid continues to build or recur, doctors may recommend chest tube drainage and chemical pleurodesis. Chemical pleurodesis is a technique in which a sclerosing agent is used to abrade the pleural surfaces producing an adhesion between the parietal and visceral pleurae. This will prevent further effusion by eliminating the pleural space. Talc appears to be the most effective agent for pleurodesis, with a success rate of nearly 95%. It is highly effective when administered by either poudrage or slurry. Poudrage is the most widely used method of instilling talc into the pleural space. Before spraying the talc, the medical team removes all pleural fluid to completely collapse the lung. After the talc is administered, they inspect the pleural cavity to be sure the talc has been evenly distributed over the pleural surface. Some doctors prefer to use talc mixed with saline solution which forms a wet slurry that can roll around the pleural cavity.

MESOTHELIOMA'S CAUSE - ASBESTOS EXPOSURE

At some point in our lives, nearly all of us have been exposed to asbestos in the air we breathe and the water we drink; from natural deposits in the earth, and from the deterioration of asbestos products around us. Most of us, however, do not become ill as a result of our exposure. More commonly, those who at some point are diagnosed with asbestos disease, have worked in jobs where more substantial exposure occurred over longer periods of time. Nevertheless, cases of mesothelioma have been documented as the result of lesser exposure, affecting family members of workers who came into contact with asbestos and brought it home on their clothing, skin or hair, or affecting those who lived in close proximity to asbestos manufacturing facilities. Symptoms of asbestos disease usually are not be apparent until decades after exposure.

Asbestos was used commercially in North America as early as the late 1800s, but its use increased dramatically during the World War II era when shipyards produced massive numbers of ships for the war effort. Since that time, asbestos-containing products were used by the construction and building trades, the automotive industry and the manufacturing industry. All told, more than 5,000 products contained asbestos.

For more than 50 years, products containing asbestos remained unregulated, and the manufacturers of those products continued to prosper, knowing full well that many of the millions of workers who came into contact with their products would ultimately suffer as the result of their actions. Finally, in the late 1970s, the Consumer Products Safety Commission banned the use of asbestos in wallboard patching compounds and artificial ash for gas fireplaces because the fiber could easily be released during use. In 1989, the Environmental Protection Agency banned all new use of asbestos, but uses established prior to that time were still allowed. Although awareness of the dangers of asbestos and public concern over the issue have led to a decline in domestic consumption over the years, a total ban on asbestos has not come to fruition. Asbestos is still imported, still used and still dangerous.

Although it is suggested that the number of mesothelioma cases in the U.S. has reached its peak and has begun to drop, a forecast released by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (SEER), in April, 2003, projected the total number of American male mesothelioma cases from 2003-2054 to be approximately 71,000. This number, however, does not take into consideration events such as the World Trade Center disaster on September 11, 2001, when millions of New Yorkers were potentially exposed to air filled with carcinogenic asbestos particles. When the latency period for asbestos disease is factored in, cases of mesothelioma will continue to be diagnosed for years to come.

Mesothelioma: Questions and Answers

Mesothelioma is a rare form of cancer in which malignant (cancerous) cells are found in the mesothelium, a protective sac that covers most of the body’s internal organs. Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles.

1. What is the mesothelium?

The mesothelium is a membrane that covers and protects most of the internal organs of the body. It is composed of two layers of cells: One layer immediately surrounds the organ; the other forms a sac around it. The mesothelium produces a lubricating fluid that is released between these layers, allowing moving organs (such as the beating heart and the expanding and contracting lungs) to glide easily against adjacent structures.

The mesothelium has different names, depending on its location in the body. The peritoneum is the mesothelial tissue that covers most of the organs in the abdominal cavity. The pleura is the membrane that surrounds the lungs and lines the wall of the chest cavity. The pericardium covers and protects the heart. The mesothelial tissue surrounding the male internal reproductive organs is called the tunica vaginalis testis. The tunica serosa uteri covers the internal reproductive organs in women.

2. What is mesothelioma?

Mesothelioma (cancer of the mesothelium) is a disease in which cells of the mesothelium become abnormal and divide without control or order. They can invade and damage nearby tissues and organs. Cancer cells can also metastasize (spread) from their original site to other parts of the body. Most cases of mesothelioma begin in the pleura or peritoneum.

3. How common is mesothelioma?

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. About 2,000 new cases of mesothelioma are diagnosed in the United States each year. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age.

4. What are the risk factors for mesothelioma?

Working with asbestos is the major risk factor for mesothelioma. A history of asbestos exposure at work is reported in about 70 percent to 80 percent of all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos.

Asbestos is the name of a group of minerals that occur naturally as masses of strong, flexible fibers that can be separated into thin threads and woven. Asbestos has been widely used in many industrial products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. If tiny asbestos particles float in the air, especially during the manufacturing process, they may be inhaled or swallowed, and can cause serious health problems. In addition to mesothelioma, exposure to asbestos increases the risk of lung cancer, asbestosis (a noncancerous, chronic lung ailment), and other cancers, such as those of the larynx and kidney.

Smoking does not appear to increase the risk of mesothelioma. However, the combination of smoking and asbestos exposure significantly increases a person’s risk of developing cancer of the air passageways in the lung.

5. Who is at increased risk for developing mesothelioma?

Asbestos has been mined and used commercially since the late 1800s. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not known. However, an increased risk of developing mesothelioma was later found among shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure in the workplace. People who work with asbestos wear personal protective equipment to lower their risk of exposure.

The risk of asbestos-related disease increases with heavier exposure to asbestos and longer exposure time. However, some individuals with only brief exposures have developed mesothelioma. On the other hand, not all workers who are heavily exposed develop asbestos-related diseases.

There is some evidence that family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases. This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers. To reduce the chance of exposing family members to asbestos fibers, asbestos workers are usually required to shower and change their clothing before leaving the workplace.

6. What are the symptoms of mesothelioma?

Symptoms of mesothelioma may not appear until 30 to 50 years after exposure to asbestos. Shortness of breath and pain in the chest due to an accumulation of fluid in the pleura are often symptoms of pleural mesothelioma. Symptoms of peritoneal mesothelioma include weight loss and abdominal pain and swelling due to a buildup of fluid in the abdomen. Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.

These symptoms may be caused by mesothelioma or by other, less serious conditions. It is important to see a doctor about any of these symptoms. Only a doctor can make a diagnosis.

7. How is mesothelioma diagnosed?

Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient’s medical history, including any history of asbestos exposure. A complete physical examination may be performed, including x-rays of the chest or abdomen and lung function tests. A CT (or CAT) scan or an MRI may also be useful. A CT scan is a series of detailed pictures of areas inside the body created by a computer linked to an x-ray machine. In an MRI, a powerful magnet linked to a computer is used to make detailed pictures of areas inside the body. These pictures are viewed on a monitor and can also be printed.

A biopsy is needed to confirm a diagnosis of mesothelioma. In a biopsy, a surgeon or a medical oncologist (a doctor who specializes in diagnosing and treating cancer) removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. If the cancer is in the abdomen, the doctor may perform a peritoneoscopy. To obtain tissue for examination, the doctor makes a small opening in the abdomen and inserts a special instrument called a peritoneoscope into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.

If the diagnosis is mesothelioma, the doctor will want to learn the stage (or extent) of the disease. Staging involves more tests in a careful attempt to find out whether the cancer has spread and, if so, to which parts of the body. Knowing the stage of the disease helps the doctor plan treatment.

Mesothelioma is described as localized if the cancer is found only on the membrane surface where it originated. It is classified as advanced if it has spread beyond the original membrane surface to other parts of the body, such as the lymph nodes, lungs, chest wall, or abdominal organs.

8. How is mesothelioma treated?

Treatment for mesothelioma depends on the location of the cancer, the stage of the disease, and the patient’s age and general health. Standard treatment options include surgery, radiation therapy, and chemotherapy. Sometimes, these treatments are combined.

• Surgery is a common treatment for mesothelioma. The doctor may remove part of the lining of the chest or abdomen and some of the tissue around it. For cancer of the pleura (pleural mesothelioma), a lung may be removed in an operation called a pneumonectomy. Sometimes part of the diaphragm, the muscle below the lungs that helps with breathing, is also removed.
• Radiation therapy, also called radiotherapy, involves the use of high-energy rays to kill cancer cells and shrink tumors. Radiation therapy affects the cancer cells only in the treated area. The radiation may come from a machine (external radiation) or from putting materials that produce radiation through thin plastic tubes into the area where the cancer cells are found (internal radiation therapy).
• Chemotherapy is the use of anticancer drugs to kill cancer cells throughout the body. Most drugs used to treat mesothelioma are given by injection into a vein (intravenous, or IV). Doctors are also studying the effectiveness of putting chemotherapy directly into the chest or abdomen (intracavitary chemotherapy).

To relieve symptoms and control pain, the doctor may use a needle or a thin tube to drain fluid that has built up in the chest or abdomen. The procedure for removing fluid from the chest is called thoracentesis. Removal of fluid from the abdomen is called paracentesis. Drugs may be given through a tube in the chest to prevent more fluid from accumulating. Radiation therapy and surgery may also be helpful in relieving symptoms.

9. Are new treatments for mesothelioma being studied?

Yes. Because mesothelioma is very hard to control, the National Cancer Institute (NCI) is sponsoring clinical trials (research studies with people) that are designed to find new treatments and better ways to use current treatments. Before any new treatment can be recommended for general use, doctors conduct clinical trials to find out whether the treatment is safe for patients and effective against the disease. Participation in clinical trials is an important treatment option for many patients with mesothelioma.

People interested in taking part in a clinical trial should talk with their doctor. Information about clinical trials is available from the Cancer Information Service (CIS) (see below) at 1–800–4–CANCER. Information specialists at the CIS use PDQ®, NCI’s cancer information database, to identify and provide detailed information about specific ongoing clinical trials. Patients also have the option of searching for clinical trials on their own. The clinical trials page on the NCI’s Cancer.gov Web site, located at http://www.cancer.gov/clinical_trials on the Internet, provides general information about clinical trials and links to PDQ.

People considering clinical trials may be interested in the NCI booklet Taking Part in Clinical Trials: What Cancer Patients Need To Know. This booklet describes how research studies are carried out and explains their possible benefits and risks. The booklet is available by calling the CIS, or from the NCI Publications Locator Web site at http://www.cancer.gov/publications on the Internet.