Peritoneal Mesothelioma Gene Expression May Predict Survival

Peritoneal mesothelioma is a rare cancer of the membranes that line the abdominal cavity.  Like other forms of mesothelioma, it is caused by exposure to fibers of the mineral asbestos.  While it is almost always fatal, people with peritoneal mesothelioma tend to exhibit very different responses to the disease.  Writing in the journal Cancer, the Maryland researchers note, "There is marked variability in its clinical behavior.  Some patients die rapidly, and others survive for many years."

The researchers set out to determine reasons for this variability and believe the answer may lie in signaling pathways that tell cancer cells to grow and proliferate.  Experimenting on tumor samples from 41 mesothelioma patients, the researchers analyzed the genes expressed by each set of cells.  What they found was an important difference in the 'signaling chemicals' that are responsible for protein synthesis and RNA production inside cells. 

In one group, the signaling pathways known as Phosphoinositide-3-kinase (PI3K) and the closely interacting mammalian target of rapamycin (mTOR) were overexpressed.  In cases where the genes produced by these pathways were present, the peritoneal mesothelioma patients had survived for a median of 24 months.

But in cases where these pathways, and their corresponding genes, were not found, the mesothelioma patients had a median survival of 69.5 months.  To further test their theory that these cell pathways were linked to cancer cell proliferation and prognosis, the researchers used a chemical to inhibit the P13K and mTOR pathways in cell samples.  They found that, when these pathways were inhibited, cell signaling and cell proliferation were significantly reduced.

Taken together, the researchers conclude that these two experiments point to the value of analyzing gene expression pathways in patients diagnosed with malignant peritoneal mesothelioma.  They write, "Targeting the PI3K and mTOR signaling pathways may have significant therapeutic value in patients with MPM." 

The study was conducted by the Division of Surgical Oncology at the University of Maryland School of Medicine in Baltimore and will be published in an upcoming issue of Cancer.

MesotheliomaWeb.org Reports Mesothelioma Symptoms

Mesothelioma, more properly known as malignant mesothelioma, is a type of cancer occurring in the mesothelial tissues. These are epithelial tissues that line the body's thoracic and abdominal cavities – also known as primordial cavities – and surround and protect the lungs, heart and abdominal organs.

 

Mesothelioma's only known cause is asbestos, and 75 percent of cases occur in the mesothelial lining around the lungs. Only about five percent of cases occur as pericardial mesothelioma, in the lining around the heart. Peritoneal mesothelioma, in the abdomen, accounts for about 20 percent of cases.

 

Medical professionals have long regarded mesothelioma as a "silent killer" disease for its tendency to lie dormant for a long period – sometimes up to 50 years – without producing any specific symptoms, after which it advances rapidly to a highly aggressive form of cancer.

 

Statistics indicate that, from 1999 to 2005, the mortality rate from this disease reached 18,068 in the U.S. alone, with 14,591 of those deaths occurring among males and the balance among females.

 

Asbestos mining and manufacture in the U.S. declined from 885,000 tons in 1973 to 1,609 tons in 2008. Today, even though asbestos mining and manufacture has moved overseas for the most part, the legacy effects of decades of U.S. use – in everything from construction products to oven gloves – cause about 10,000 American deaths a year, 2,500 of those from mesothelioma. This puts it on a footing akin to skin cancer in terms of commonality, according to one source.

 

Asbestos fibers get into the body, and the mesothelial tissues, either by inhaling or by ingesting. This can be as simple as swallowing saliva, and – because the body can't get rid of asbestos fibers the way it does some other toxins – the fibers remain, creating irritations that lead to tissue lesions and, in some instances, to malignant tumors.

 

Mesothelioma is exacerbated by smoking. When it begins displaying typical symptoms early in life (i.e., at age 30 or before), the course of the disease is more rapid and more aggressive than it is among those who display symptomatology near or during their retirement years.

 

The symptoms of mesothelioma vary, of course, with location. Victims of pleural mesothelioma may experience a hacking, dry cough or coughing up blood. They may also have difficulty swallowing. In some cases, night sweats or fevers of unknown etiology may also occur. Fatigue is quite common, as is weight loss as the disease progresses and sufferers begin to have difficulty breathing, even when resting.

 

At this stage, pains in the chest, diaphragm or rib area begin to manifest, possibly along with tangible lumps under skin on the chest. In addition to difficulty, breathing may itself become painful.

When mesothelioma occurs in the abdomen, similar symptoms occur, though patients are unlikely to experience significant difficulty breathing, and the pain – instead of being in the chest – is in the abdomen. Peritoneal mesothelioma sufferers will instead experience abdominal symptoms, including diarrhea or constipation, nausea, and possibly vomiting. Fatigue remains a constant, as it does with almost all forms of cancer.

Pericardial mesothelioma produces symptoms that are site-specific; e.g., an irregular heartbeat and chest pain. It also causes difficulty breathing, fever of unknown origin, night sweats and fatigue.

If patients are sufficiently healthy, doctors may recommend surgery, radiation or chemotherapy, alone or in combination, though these treatments are largely viewed as palliative rather than curative; that is, improving breathing and reducing pain, though not actually eradicating the tumor.

These treatments succeed in adding only a few months to the typical mesothelioma patient's prognosis, which is about one year to live. However, newer treatments like gene therapy and photodynamic therapy (the use of light) show improved prognoses.

Oncologists are also experimenting with multimodal treatments via clinical trials, and there is hope that a "perfect storm" of methods will eventually be discovered that eradicates mesothelioma entirely.