A significant amount of research is dedicated to finding more effective approaches to malignant mesothelioma. Scientists are trying to determine the best surgical techniques, create better diagnostic tools and test the effects of various chemotherapy drugs. At Kazan, McClain, Lyons, Greenwood and Harley, we keep our ears to the ground for you, and we are excited about what we are hearing.
For example, some researchers decided to focus their investigation on improving the performance of the tools that are already available, such as cisplatin, which is one of the most common medications prescribed for mesothelioma patients. One team from Switzerland found that short-term starvation may actually give cisplatin a boost, according to a new study appearing in the journal BMC Cancer.
What does cisplatin do for mesothelioma patients? Individuals who have been diagnosed with malignant mesothelioma share certain things in common. Asbestos exposure was a likely cause of your condition. Respiratory difficulties are a prominent problem. If you were not aware that you were developing the disease until its symptoms manifested, you were probably diagnosed while the cancer was in its advanced stages. With all these similarities, you would expect that all patients with your illness would respond the same way to the same treatments. Unfortunately, this is not true. Not all mesothelioma patients react equally to chemotherapy, radiation or surgery. One of the most important reasons for this is that the diseased tissues in patients may be genetically different. At Kazan, McClain, Satterley, Lyons, Greenwood & Oberman, we keep track of the most promising advances in the medical field. One active area of scientific research, known as personalized medicine, is giving scientists hope that they can treat patients more effectively. Personalized medicine is shifting the focus in cancer However, Edward Benz, Jr., M.D., the president of the Dana-Farber Cancer Institute, discussed new ways of thinking about malignant diseases in a blog post on the website for Stand Up To Cancer, an advocacy group that supports basic research. He noted that in recent years, scientists started understanding that tumors in individual patients, even when they are the same type of cancer, may have important differences that can impact the success of treatment. For example, women who have breast cancer have diseased cells that may be classified according to the presence or absence of a cell receptor that responds to hormones and hormonal treatments. Additionally, women can have certain mutations in specific genes that can make them more likely to develop breast cancer or other malignancies. Knowledge of these mutations can help doctors determine whether certain women need to be monitored more closely. These approaches are part of what is known as personalized medicine, in which treatments can be tailored to patients at the individual level rather than with sweeping, broad strokes. How can mesothelioma patients benefit from personalized medicine? For example, one team of scientists from around the U.S. released a study in 2004, which demonstrated how a panel of 27 genes helped doctors predict survival time among mesothelioma patients who underwent surgery. By 2009, researchers from this team refined this approach further by predicting survival among surgical patients with the help of a four-gene expression ratio test. “Patients whose gene ratio test results predict a good prognosis after surgery may more confidently select the treatment option that includes surgery,” Raphael Bueno, M.D., and his colleagues wrote in their study. Knowing who to operate on could be important because such procedures are invasive and, if approached haphazardly, can actually hurt patients. The search continues “For all its promise, the field of cancer genomics is less than a decade old. The progress in mapping out cancer’s genetic variety, though substantial, is still at a relatively early stage,” Benz wrote in his blog. “As we fill in the map and develop a new taxonomy for cancer – a new system for distinguishing tumor types and subtypes – the advances promise to be enormous. But we are still learning how to use these powerful new tools. Much remains to be done.” And we, along with our clients, can’t wait to see what comes next. Related posts: Mesothelioma Clinical Trials: What They Are, How They Work, How to Participate Mesothelioma Treatment by Stage Current Mesothelioma Treatment Research and Studies An 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 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 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. In celebration of the meeting of the International Mesothelioma Interest Group’s recent meeting in Boston, at iMig 2012, we at Kazan, McClain, Lyons, Greenwood and Harley funded this year’s Young Investigator Awards, as we have done at each meeting since 2008. This is the third in a series of entries discussing the promising work of one of the recipients. Researchers from the University of Toronto are figuring out how to use the body’s own immune system to boost the efficacy of chemotherapy in the treatment of malignant mesothelioma. Dr. Licun Wu, one of the scientists heading this work, was kind enough to sit down with us and discuss this exciting approach to medicine. Activating the body’s defenses In their laboratory, Wu and his team are focusing specifically on the behavior of the immune system between cycles of chemotherapy. “Cancer cells tend to repopulate during the breaks between chemotherapy treatments. Evidence has shown that the rate of repopulation of surviving cancer cells accelerates over time, so better approaches to stop this process need to be developed,” said Wu. The research team’s experiments revealed that blocking the actions of CTLA-4, a protein that acts as a brake on certain immune responses, helps prevent mesothelioma cells from repopulating during breaks in chemotherapy. Reining in this protein may allow a type of immune cell known as natural killer T cells to flourish and fight the disease. This study potentially lays the groundwork for clinical trials that use CTLA-4 blocking medications. We at Kazan Law are happy to support this research, as we know that diversifying the types of treatments available to mesothelioma patients will do them a world of good by giving them more than one way to fight this disease. Related posts: International Mesothelioma Interest Group 2012 Young Investigator Award Recipient Karin Schelch International Mesothelioma Group 2012 Young Investigator Award Recipient Yuen Yee Cheng In celebration of the meeting of the International Mesothelioma Interest Group, or iMig 2012, we at Kazan, McClain, Satterley, Lyons, Greenwood & Oberman funded this year’s Young Investigator Awards, as we have done at each meeting since 2008. This is the second in a series discussing the promising work of one of the recipients. Australia was once home to one of the world’s most thriving asbestos industries, which left behind a dubious legacy of health problems. Fortunately, a generation of scientists decided to respond to this legacy by establishing the Asbestos Diseases Research Institute (ADRI), located at the University of Sydney. At iMig 2012, we had the pleasure of meeting Dr. Yuen Yee Cheng, who was happy to discuss her work on epigenetics and the suppression of malignant pleural mesothelioma (MPM) tumors. Silencing the disease Cancer is a complex condition that is influenced by a wide number of variables, including lifestyle choices, genetics and pollution. When it comes to MPM, the main driving factor in the development of the disease is a history of asbestos exposure, which can cause pathological changes in the mesothelial cells of the lungs. Healthy mesothelial cells contain an active gene known as ZIC1, which plays an important role in suppressing behavior that could lead to the development of tumors. Past studies have shown in gastric and colorectal cancer cells, ZIC1 was silenced. In order to determine if the same was true in MPM, Cheng and her team conducted a study that looked at cell and tumor samples. Results showed that the activity of ZIC1 was hampered in 16 of 24 MPM tumor samples, leading to the production of microRNAs (a type of chemical messenger within a cell) that are associated with disease activity. However, stimulating the expression of ZIC1 reduced the levels of these abnormal microRNAs, which interfered with the tumor growth. This is an important observation because it may inspire researchers to take a new approach toward treating MPM. This disease is not going away any time soon. In fact, the Environmental Working Group predicts that we may even see more cases of it popping up in years to come. Thankfully, scientists at places like ADRI are up to the task of solving these problems – and we are happy to support their work. “My ultimate aim is to find a cure for mesothelioma,” Cheng told us. “I would like to thank the ADRI and the Asbestos Diseases Foundation of Australia for their support. And I would sincerely like to thank the professional law corporation Kazan, McClain, Satterley, Lyons, Greenwood & Oberman for supporting the Young Investigator Award.” Related posts: International Mesothelioma Interest Group Young Investigator Award Recipient Licun Wu International Mesothelioma Interest Group 2012 Young Investigator Award Recipient Karin Schelch In celebration of the meeting of the International Mesothelioma Interest Group, or iMig 2012, we at Kazan, McClain, Satterley & Greenwood funded this year’s Young Investigator Awards, as we have done at each meeting since 2008. This is the first in a series discussing the promising work of one of the recipients. If there is one thing that defines a researcher, it is a never-ending desire to improve upon science’s current body of knowledge. When it comes to the search for a cure for malignant pleural mesothelioma (MPM), this drive usually means good news for patients. At iMig 2012, we met Karin Schelch, a PhD candidate in molecular biology, who was kind enough to talk to us on video about her team’s research on fibroblast growth factors (FGF) and fibroblast growth factor receptors (FGFR). Both sets of these proteins may serve as targets for MPM treatments. Defining the roles of the proteins in MPM According to Schelch, FGF is important for the growth and survival of cells. However, it can also drive the development of several types of malignancies. Despite this knowledge, the specific role of FGF in MPM had not always been entirely clear. This makes FGF and FGFR important topics for research because a better understanding of their biology can, in turn, lead to a better understanding of how to tackle mesothelioma. In the laboratory, Schelch and her team conducted several experiments that included MPM cell models, normal mesothelial cells and human tissue samples. Specifically, the researchers were looking at what cells made what proteins. Ultimately, they found that MPM cells and tumorous tissues have three abnormally active genes: FGFR1, FGF2 and FGF18. Through different experiments, the scientists discovered that stimulating the cells with FGF2 made them more invasive, and that blocking the actions of FGFR1 made the spread and survival of cancer cells more difficult. “Our data show that blocking the fibroblast growth factors could be a new and more efficient option for mesothelioma treatment,” Schelch told us. Furthermore, one experiment revealed that diseased cells that are resistant to cisplatin, a standard medication for MPM, are also more sensitive to FGFR1 inhibition. This is good news, considering that Schelch and her team theorize that blockage of FGFR1 could work well in combination with chemotherapy and radiation treatments. These results were so exciting that the team presented this study at iMig 2012. And on behalf of MPM patients everywhere, we are happy to support work like this. Related posts: International Mesothelioma Interest Group Young Investigator Award Recipient Licun Wu International Mesothelioma Group 2012 Young Investigator Award Recipient Yuen Yee Cheng If you’ve been newly diagnosed with malignant mesothelioma, you already know that you’ll have to make some major adjustments. While there is no cure for this disease, there are different treatments that can make life as functional and comfortable as possible. Chemotherapy is one of the regimens most commonly used to help patients. However, this treatment can cause side effects. Among them? Chemo brain. Fog and forgetfulness while fighting disease According to the National Cancer Institute, it’s not uncommon for patients who are fighting malignant diseases to experience confusion, depression or forgetfulness – all of which can be possible side effects of chemotherapy. Medical experts have a hard time agreeing on how common chemo brain is among patients taking these medications. Scientists from the University of California, Los Angeles (UCLA) point out that estimates range from 25 to 82 percent. But one thing is certain: Chemo brain is real. In order to understand why cancer patients have these neurological symptoms, UCLA researchers conducted an experiment in which they imaged the brains of three groups of women: breast cancer patients who had chemotherapy, those treated with surgery and healthy women who never had breast cancer or chemotherapy. The cortical images taken during this experiment showed that blood flow and metabolism were different in the brains of patients who had chemotherapy. Later, when the test subjects were taking memory tests, brain scans showed that the chemotherapy patients’ brains had to work harder, compared to those of the healthy women. There are ways to deal with chemo brain At Kazan, McClain, Lyons, Greenwood and Harley, we’re committed to helping all of our clients who have mesothelioma cope with the changes in their lives as best as we can. From the Mayo Clinic, we’ve learned about several ways that people with mesothelioma can deal with chemo brain: When you’re taking care of a loved one with malignant pleural mesothelioma (MPM), each decision is difficult. How can I keep them comfortable? Where can we get medical consultations or legal advice? Should we think about the full round of treatments or stay more conservative? At Kazan, McClain, Lyons, Greenwood and Harley, we’ve spent more than three decades helping people make tough but informed choices. One of the more difficult decisions out there is whether to pursue surgery for mesothelioma. Some doctors are adamant that radical operations (like the extrapleural pneumonectomy, or EPP) will not cure the disease, while others emphasize that such procedures do provide pain relief and may extend survival time. For those weighing the idea of surgery for MPM, here is a quick summary of some of the arguments for and against. This is by no means a complete list. To make a fully informed decision, talk with your oncologist and/or surgical specialist before making any decisions. How surgery can help Most public health agencies agree that, even for a disease as virulent as mesothelioma, surgery has several notable benefits. The first is that it can lengthen a loved one’s life by months, if not years. The National Cancer Institute (NCI) estimates that patients who receive surgery for MPM live an average of 16 months beyond their diagnosis. Of course, survival time depends on several things. First, the earlier a patient’s disease is caught, the longer they may be expected to live. In a study published in the Journal of Thoracic and Cardiovascular Surgery, researchers determined that patients with Stage I or II mesothelioma had much better odds of surviving two, three or even four years, compared to those with Stages III or IV. The same report noted that pleurectomy/decortication and EPP are the two operations associated with the highest likelihood of prolonged survival. Another benefit of surgery is that it often provides comfort for mesothelioma patients. In fact, the NCI currently categorizes all MPM procedures as palliative, meaning they do not cure the disease but they may ease chest pressure and make breathing easier. There are a number of operations for MPM, some more extensive than others. A thoracentesis, in which fluid is drained from the pleura, is one of the simplest and most common procedures. More radical is the pleurectomy/decortication, which involves the removal of one lung and as much tumor mass as possible. Finally, the EPP is the most radical, removing as it does a lung, the lung and heart linings, and most of the diaphragm. Each surgery may provide pain relief or extend survival. How surgery can be counterproductive Sadly, not all operations for MPM increase a patient’s lifespan – or, if they do, it may be by a matter of weeks or months only. In the British Journal of Surgery, a pair of surgeons summarized the difficulties by pointing to Lionel Shriver’s memoir of dealing with MPM, titled So Much for That: She plots the course, from diagnosis to death, of a woman with abdominal mesothelioma in present-day America. Fourteen months after being given a one-year expectation of life, her doctors run out of options and the family runs out of money. The oncologist comforts her bankrupt husband saying “we’ve probably extended her life a good three months.” The bitter irony of “good” strikes the spouse, but seems lost on the doctor. Such situations are not the standard, but they do happen. It is best to know that while surgery can (and often does) help, it also may not. Consider whether doctors believe an operation will make your loved one more comfortable. Talk to them, take some time to think about it and, in the end, do what you think is best. Because malignant pleural mesothelioma (MPM) is such a tough disease to treat, it’s easy to feel like there’s little or nothing that patients have going for them. Fortunately, this isn’t true. At Kazan, McClain, Lyons, Greenwood and Harley, we make it our business to see that MPM patients have an advocate, someone who helps them learn their complete legal and medical rights. Making fully informed decisions about care and treatment is essential for people with mesothelioma. Meanwhile, from the clinical end, researchers are making exciting new finds practically every month, many of which directly affect mesothelioma patients and their families. Consider an award-winning presentation given at this year’s British Thoracic Oncology Group Conference. In it, researchers announced that diagnostic tissue tests for mesothelioma are getting better and better. The ‘changing face of mesothelioma diagnosis’ Delivered by a team of British doctors from the Glenfield Hospital in Leicester, the poster session won one of the conference’s runner-up prizes, out of a field of 200 entries. So, what did they say? The team addressed the “changing face of mesothelioma diagnosis,” concluding that it is shifting toward earlier, more thorough diagnoses. Even though it may seem like cases of MPM have been confirmed in the same manner for the last 30 or 40 years, researchers said that’s not the case. In fact, in just the past decade, the diagnostics that oncologists use for MPM have undergone a seismic shift. The authors proved as much by analyzing every case of mesothelioma reported in Leicester, England, between 2000 and 2010. The results of some basic number crunching indicated a major change in the ways oncologists find MPM. Over a decade, histology makes a big leap To start, researchers noted that nearly all cases of mesothelioma are now confirmed histologically – that is, under a microscope. Their data showed that while in 2000 just three-quarters of cases involved doctors examining cell samples up close, by 2010 that figure had jumped to 96 percent. Likewise, the proportion of cases diagnosed during post mortem exams plummeted from 34 percent to just 4 percent. What do these changes mean? Basically, more cases are being confirmed in a thorough manner, while fewer are dying before diagnosis. The team also noted that the kinds of diagnostic tests being used are shifting: “Pre-mortem histological diagnostic confirmation has significantly increased in the past five years compared to the previous five years and is now achieved in [more than] 95 percent of our patients,” the group concluded. “This is due to increased use of CT-guided pleural biopsy and medical thoracoscopy.” What does this mean for patients? There are several positive findings in this study. The first is that, by using tissue sampling and microscopic cell staining, doctors are diagnosing more cases of MPM during patients’ lifetimes, making people with mesothelioma more likely to get a solid prognosis and have access to proper treatments and palliative care. The poster session also indicated that histological staining can adequately confirm the presence of MPM, sparing many patients the experience of undergoing an invasive diagnostic surgery. Finally, it’s nice to know that the methods doctors use to diagnose mesothelioma are getting more sophisticated all the time. In 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: Researchers concluded that CK2-alpha may be a novel target for respiratory cancer treatments.
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Personalized medicine may brighten outlook on mesothelioma research and treatment
Currently, most patients (and even some medical professionals) think of cancer in terms of the organ or tissue from which it originates. For example, people are familiar with prostate cancer, breast cancer, liver cancer, lung cancer and so on. They also think of leukemia as affecting the blood-forming cells of the bone marrow.
The reason why personalized medicine can be valuable for people with mesothelioma is that it can help doctors determine which therapeutic approaches may be the most appropriate for different patients.
While personalized medicine sounds promising for mesothelioma patients, this scientific advance is still relatively young.Scientists Study Proteins as Potential Mesothelioma Markers
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.
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.International Mesothelioma Interest Group Young Investigator Award Recipient Licun Wu
Several medical experts are exploring ways to use the body’s immune system to kill malignant cells, according to the American Cancer Society. These approaches, collectively known as immunotherapy, may act directly on the cancer or support the actions of healthy cells.International Mesothelioma Group 2012 Young Investigator Award Recipient Yuen Yee Cheng
International Mesothelioma Interest Group 2012 Young Investigator Award Recipient Karin Schelch
Mesothelioma Patients can Learn to Cope with ‘Chemo Brain’
Families of Mesothelioma Patients Face Tough Choices When Weighing Surgical Options
Award-Winning Study Shows that Mesothelioma Tissue Tests are Improving
Landmark Study Implicates Enzyme in Respiratory Cancers Like Mesothelioma