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UCSF Thoracic Oncology Laboratory

Scientists Study Proteins as Potential Mesothelioma Markers

diagnosisAn early diagnosis is one of the first steps toward overcoming a potentially fatal disease. When it comes to malignant pleural mesothelioma (MPM), there are few reliable methods of detecting this illness, particularly while it is in its early stages. This makes medical research all the more important.

Recently, a team of scientists from the University of California, San Francisco (UCSF) conducted a study with help from the Estate of Robert Griffiths; the Jeffrey and Karen Peterson Family Foundation; and Paul and Michelle Zygielbaum, all of whom provided funds via The Kazan, McClain, Abrams, Fernandez, Lyons, Greenwood, Oberman, Satterley & Bosl Foundation, Inc, which gave additional support, as well. For the experiment, the researchers evaluated the utility of three different proteins as potential biomarkers of malignant mesothelioma.

A pressing need for better detection
The median survival time following diagnosis of mesothelioma is 16 months, according to the National Cancer Institute. This disease is usually a consequence of identifiable asbestos exposure. However, because the latency period between contact with the material and the development of symptoms can take upward of 20 years, the incidences of asbestos-related illnesses will continue to rise for at least the next decade as the population of senior citizens increases, according to the Environmental Working Group.

Doctors are usually able to treat diseases effectively if they identify them early. This has proved to be a rather difficult goal for MPM. According to the American Cancer Society, most patients do not even know they are sick until they develop symptoms. Some physicians try to diagnose these individuals with the help of chest X-rays or computed tomography. However, it is not clear whether these tools are useful.

Signs of disease in the cells
One active area of research into the diagnosis of MPM is biomarkers, which are substances in the body that indicate the presence of disease. Based on previous studies, scientists from UCSF decided to investigate whether the proteins dishevelled-3 (Dvl3), excitatory amino acid transporter 1 (EAAT1) and glutamine synthetase (GS) could help identify MPM.

In their experiment, the researchers collected tissue samples from 39 MPM patients. They also obtained cell samples from both MPM and healthy mesothelial tissue. Among the various laboratory tests that they performed was cell staining to reveal the biomarkers.

“According to the results in this study, our findings indicate that MPM cells express more EAAT1 than normal cells. Moreover, the survival time of MPM patients was inversely correlated with the degree of EAAT1 staining: the stronger the staining, the shorter the survival time,” the researchers wrote in the Journal of Clinical Pathology.

Other results showed that both Dvl3 and GS staining were associated with EAAT1 staining, but only Dvl3 was linked to survival time. Further studies are needed to verify these findings.

Landmark Study Implicates Enzyme in Respiratory Cancers Like Mesothelioma

medical researchersIn the world of experimental, targeted mesothelioma treatments, scientists have thousands of potential targets to work with. Literally – since, according to Shayne Cox Gad’s Handbook of Pharmaceutical Biotechnology, the human body contains at least 3,000 unique enzymes and 40,000 discrete proteins. While some of these molecules have nothing to do with malignant growth, others have been tied to the genesis of specific cancers.

CK2-alpha is one such enzyme. In a landmark study published in the journal PLoS ONE, researchers from the Thoracic Oncology Laboratory at the University of California, San Francisco (UCSF) became the first team to link CK2-alpha to a cellular signalling pathway that can cause respiratory cancers if uncontrolled.

This knowledge may contribute to better treatments for malignant pleural mesothelioma (MPM).

The first domino to fall

According to the report, CK2-alpha is responsible for “switching on” at least 300 separate proteins in the human body. Hence, this enzyme is so important for the delicate balance of cell growth and death that (researchers reasoned) CK2-alpha could easily lead to cancers if it went haywire.

The team explained that, in a number of malignancies, CK2-alpha levels are higher than normal. In fact, cancers that have very high CK2-alpha concentrations often have poorer prognoses.

Why? Well, without being sure, a number of oncologists have suspected that this enzyme can set off a cascade of cellular effects that cause uncontrolled growth.

To do so, overactive CK2-alpha seems to work through the Hedgehog (Hh) family of proteins – namely, the Indian, Desert and Sonic Hedgehog trio. (And yes, the latter is named for a video game character.) Hh proteins control organ development and stem cell growth. When CK2-alpha levels jump – possibly due to asbestos exposure – the enzyme probably cranks up the activity of the Hh proteins, leading to the creation of cancerous stem cells.

At least, that was the theory. Now, the UCSF team has essentially proved it.

Establishing it three separate ways

In cementing CK2-alpha’s role as an Hh destabilizer and respiratory cancer generator, the group went about it in three distinct ways:

  1. They analyzed 100 separate cancer tissues and established that the levels of CK2-alpha often match those of Gli1, a protein that, to put it crudely, does the Hh proteins’ dirty work.
  2. The team used chemicals to shut off CK2-alpha activity in cancer cells. This resulted in lower levels of Gli1. It also led to lower levels of cancer stem cells in the tissue.
  3. The UCSF group tried the opposite, cranking up CK2-alpha production. This led, as they suspected, to an overabundance of Gli1.

Researchers concluded that CK2-alpha may be a novel target for respiratory cancer treatments.

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