Substance Found in Turmeric Packs Powerful Punch against Mesothelioma

Curcumin, a naturally occurring polyphenol in turmeric, is being studied for its possible application in the treatment and prevention of mesothelioma. Turmeric has long been believed to have anticancer properties due to its antioxidant and anti-inflammatory properties.

Researchers at the University of Vermont found that curcumin caused pyroptotic cell death in both mouse and human in vitro models with malignant mesothelioma cell lines. Cell death was induced by the activation of the enzyme caspase-1, and the increased release of high-mobility group box 1 (HMGB1), a nuclear protein responsible for organizing DNA and regulating transcription.

Researchers blocked production of pro-inflammatory cytokines IL-1β and IL-18 by inhibiting the NF-κB pathway, a protein responsible for cytokine production and cell survival which has been linked to cancer, inflammatory and autoimmune diseases.

The researchers also found that the curcumin not only caused mesothelioma cell death, but also protected against inflammation, which could ultimately protect against the spread of the disease.

It should be recognized that the study involved direct delivery of curcumin to mesothelioma cancer cells, and did not attempt to determine the impact of eating turmeric on patients diagnosed with mesothelioma.

You can view the abstract here.

Paclitaxel Nanoparticles to Treat Late Stage Peritoneal Mesothelioma

A group of graduate students and postdoctoral fellows at Boston University are trying to find a better treatment for late-stage peritoneal mesothelioma. The group is developing a method to deliver chemotherapy drugs directly to tumor cells with nanoparticles which are absorbed by the tumor cells and release the drugs. The detailed study published February 4, on the BU College of Engineering site is part of a four part series detailing current research projects being performed by the Grinstaff Group.

The Grinstaff Group chose to focus on peritoneal mesothelioma because it is easier to isolate and does not metastasize like other cancers, theoretically making it easier to attack with an innovative drug delivery system, in this case - nanoparticles loaded with paclitaxel, a chemotherapy drug commonly used to treat mesothelioma.

The nanoparticles are composed of squiggly polymer chains that intertwine and compress into smooth, compact spheres, with the paclitaxel trapped within the chains. When the nanoparticles are exposed to a more acidic environment, the chains loosen allowing water to enter and causing the nanoparticles to expand and release the paclitaxel. Cells “eat” material outside their walls by encircling them within pockets that are acidic to aid in digestion. The researchers hypothesized that the cells would ingest the drug-loaded nanoparticles, expand, and release the drug.

Working with Yolonda Colson, a thoracic surgeon at Brigham and Women’s Hospital and a Harvard Medical School professor of surgery, the researchers injected paclitaxel-loaded nanoparticles in mice with established mesothelioma tumors. One group of mice had paclitaxel injected into the abdominal cavity, one group was injected with drug-free nanoparticles, and a third group was injected with paclitaxel-loaded nanoparticles.

Two weeks after the injection was administered the tumors were surgically removed, the paclitaxel-loaded nanoparticle treated tumors had almost no mass, while the tumor mass of the other two groups was around two grams. The team then administered one dose a week of the same therapies for an entire month, and found that the median survival of mice receiving the paclitaxel-loaded nanoparticles was twice that of the other two groups, with two-thirds showing no tumors at all.

Clinical trials have yet to be performed, but the group is hopeful that nanoparticles could supplement the current chemotherapy treatment, or possibly replace it entirely. “This project is so close to something where we can actually have a benefit for people in the clinical setting and help people in the next five to ten years,” Aaron Colby, a research student working on the project says.

In 11 years, three of the Grinstaff Group’s projects have been commercialized, and at least four privately held biotech companies have spun off from research which started under The Grinstaff Group.

Recent Advances in Mesothelioma Research Target Proteins within the Body

Science Daily reported on two recently published studies which both focus on therapies for mesothelioma that target the protein p53 within the body. P53 is responsible for regulating cell growth and the repair of damaged cells, but becomes inactive in most human cancers due to alterations in its pathway.

The first study was lead by pathologist Antonio Giordano, Director and Founder of the Sbarro Health Research Organization in Philadelphia, Pennsylvania, and Professor of Pathology and Oncology at the University of Siena, Italy. The researchers used a drug called RITA with another drug, both designed to reactivate p53 which is vital for tumor suppression. The drug combination proved to be very toxic to the mesothelioma cells, but not to healthy cells. The researchers also found that the RITA combo worked synergistically with cisplatin, the most common chemotherapy drug used to treat mesothelioma.

The RITA combination induced apoptosis (cell death) in epitheloid mesothelioma cell type cell lines, but the more aggressive sarcomatoid cell type of mesothelioma was not responsive. "It remains to be seen whether the combination of RITA with other activators of apoptosis can achieve efficacy also against the more aggressive cases," says Alfredo Budillon, Head of the Experimental Pharmacology Unit of the National Cancer Institute of Naples and coauthor of the study.

The second study was led by Paola Indovina of the University of Siena and the Sbarro Institute for Cancer Research and Molecular Medicine, Temple University in Philadelphia. In this study the researchers tested a new drug called MK-1775, which is currently being tested in clinical trials for other types of tumors, in combination with cisplatin designed to inhibit the protein WEE1 which is crucial in the process of repairing damaged DNA before cells divide. This study also focused on the protein p53, when p53 is inactive due to the presence of cancer cells, the WEE1 protein allows cancer cells to repair themselves after exposure to genotoxic agents like chemotherapy drugs. When MK-1775 inhibits the WEE1 protein, it allows the cisplatin to interrupt a crucial step in the cancer cell division process. The damaged cancer cells are still able to divide, but experienced apoptosis as a result of the interruption.

Mesothelioma is a particularly aggressive cancer, by attacking the mechanisms that allow the rapid growth and spread of the disease within the body it will hopefully reduce the extremely high rate of recurrence and give patients a better prognosis and quality of life. 

OSHA Issues New Asbestos Fact Sheet

The Occupational Safety and Health Administration (OSHA) has issued a new Asbestos Fact Sheet at the urging of Linda Reinstein, President, CEO and Co-Founder of the Asbestos Disease Awareness Organization (ADAO).

On July 22, 2013 Linda met with Dr. David Michaels, Assistant Secretary of Labor for OSHA to discuss asbestos hazards and the need for additional resources to educate and to protect the public from asbestos-related diseases.

The resulting Fact Sheet summarizes the hazards involved when asbestos fibers are released into the air. It highlights where the hazards may occur, including cleanup after natural disasters, during the manufacturing of asbestos-containing products, during renovations, construction and shipyard work to name a few.

The fact sheet also defines OSHA Standards to protect workers from exposure to asbestos fibers in many types of work places. And what protections exist for these Standards, including permissible exposure limits, assessment of workplaces, monitoring exposure levels, hazard communication, training and medical requirements for each industry.

OSHA notes that this fact sheet is one in a series of informational fact sheets highlighting their programs, policies or standards. It does not impose any new compliance requirements.

We commend Linda for her tireless efforts to educate the public on the hazards of asbestos. Linda lost her husband Alan in 2006 to malignant pleural mesothelioma and fought back by becoming one of the most influential voices in the ban asbestos movement.

For more important information on asbestos from OSHA, please visit here.

Source: OSHA Listens and Takes Action: New Asbestos Fact Sheet

Pacific Meso Center Receives $100,000 Donation to Fund Stem Cell Mesothelioma Research

LOS ANGELES, Jan. 13, 2014 /PRNewswire/ -- The Pacific Meso Center (PMC), a Division of The Pacific Heart, Lung & Blood Institute (PHLBI), is pleased to acknowledge a generous $100,000 donation from Roger G. Worthington of the Law Office of Worthington & Caron, PC to fund the Center's Mesenchymal Stem Cell Program. The goal of this unique research project is to develop innovative treatments for malignant pleural mesothelioma, an asbestos-related cancer affecting the lining of the chest.

Mesenchymal stem cells are potent cells found in a variety of tissues, i.e., bone marrow, placenta, and others and can grow and mature into a variety of different cell types. Scientists recently have found that mesenchymal stem cells easily can be harvested from discarded human placentas and this observation has opened a new chapter in stem cell medicine.

Mesenchymal stem cells already are utilized in FDA-approved therapies to modify serious inflammatory autoimmune diseases. "Placenta-derived mesenchymal stem cells are intriguing because they, like the placenta, are not easily recognized by the body as foreign tissue, which makes them an excellent source of universally-compatible stem cells for use in cancer therapy," said Dr. Robert Cameron, Scientific Advisor at the PMC, Director of the UCLA Comprehensive Mesothelioma Program, and Chief of Thoracic Surgery at the West Los Angeles VA Medical Center. "Modified mesenchymal stem cells can serve as a vehicle for delivering a wide range of molecular and gene therapies directly to the site of cancer, and may be particularly useful in mesothelioma, thymoma, and lung cancer. We plan to test the effects of mesenchymal stem cells on multicellular tumor spheroids -- a custom designed 3-D model for studying mesothelioma treatments in the laboratory."

"After a patient undergoes mesothelioma surgery, much of the tumor is excised, but some cancer cells inevitably remain," Dr. Cameron noted. "To destroy the remaining cancer cells, modified mesenchymal stem cells can be delivered to the exact location where the cancer was surgically removed and destroy any residual cancer cells. This cutting-edge strategy has the potential both to increase the chance of long-term survival and eliminate current treatments with significant side effects, such as radiation and chemotherapy."

"We certainly are pleased to provide the funds to begin this groundbreaking research which holds immense potential to lead to effective treatments not only for mesothelioma but perhaps for many other cancers as well," said Roger Worthington, long-term supporter of the PMC and principal of the Law Office of Worthington and Caron PC.

Clare Cameron, Executive Director of PHLBI, was pleased to accept the donation. "Although this generous gift will get this important research off the ground, we ultimately need additional funds before we can translate this work into a reality for doctors and patients," Ms. Cameron pointed out. "We encourage everyone who can to contribute so that we can speed this development on before even another single person loses his or her battle with this horrible disease."

For more information about the Pacific Mesothelioma Center, please click on www.phlbi.org/divisions/lung-disease/pacific-meso-center.

Roger Worthington, Esq. can be reached via www.mesothel.com or by phone at 800.831.9399.

Recent Study Confirms Effectiveness of Radiation Therapy Following Lung-Sparing Pleurectomy/Decortication Surgery

There has been a long-standing debate over which surgery is more effective for treating malignant pleural mesothelioma (MPM). For many years, a majority of surgeons believed that a radical procedure called Extrapleural Pneumonectomy (EPP), which involves removal of the mesothelioma tumor along with the affected lung, diaphragm and pericardium, was the preferred way of surgically treating MPM. However, in recent years, many surgeons have come to the realization that the Pleurectomy/Decortication (P/D) procedure innovated by UCLA and West Los Angeles VA Medical Center Thoracic Surgeon Dr. Robert Cameron, in which the tumor is removed and the patient is left with a functioning lung, is the more effective and less risky procedure.

For the surgeons that continue to perform EPP despite the mounting studies confirming the effectiveness of lung-sparing P/D, one of the reasons they cite to is the purported inability to effectively deliver radiation to the area following P/D.

The typical protocol following both EPP and P/D is to have patients undergo a series of radiation treatments, typically 25, beginning a month or so after the surgery. The purpose of the radiation treatments is to eradicate the microscopic tumor cells that remain after all visible tumor is removed. It has been the belief of EPP proponents that radiation treatments following P/D are much less effective because of the presence of the lung and related tissues.

A study published in the November edition of the international journal Lung Cancer disproves this theory. Researchers at the Centro di Riferimento Oncologico di Aviano in northern Italy monitored 20 patients with malignant pleural mesothelioma who were given localized high dose radiation therapy following P/D surgery. The patients underwent 25 radiation treatments likely over the course of five weeks. The survival rate in the study was 70 percent at two years and 49 percent at three years or more, with a median survival rate of 33 months. The estimated progression-free survival rate was 68 percent at two years and 46 percent at three years.

The results of this study confirm what proponents of P/D have believed for some time, namely that it is possible to deliver full dose radiation following lung-sparing surgery.

Related Links:

• Lung-Saving P/D vs. Radical EPP
• Debunking the Myths about P/D
• Surgical Choices: Pleurectomy with Decortication

Pennsylvania Supreme Court Rules That Asbestos Disease Claims Can Be Maintained Against Former Employers

We are pleased to announce that the Pennsylvania Supreme Court recently issued a landmark decision in favor of our clients, the heirs and estate of John “Jack” Tooey.

From 1964 to 1982, Mr. Tooey worked as an industrial salesman for Ferro Engineering, a division of Oglebay-Norton Co. (Ferro/Oglebay). As part of his job responsibilities, Jack was exposed to asbestos from a variety of products used at the steel mills he visited in Pennsylvania, West Virginia, Ohio, Michigan and Indiana, including but not limited to asbestos-containing products manufactured by Ferro/Oglebay.

Jack was diagnosed with malignant pleural mesothelioma in December 2007 at the age of 76, and passed away less than a year later. A lawsuit was filed on behalf of Jack and his wife in March 2008 against multiple defendants, including Jack’s former employer Ferro/Oglebay.

As is the case with most other states, the law in Pennsylvania provides that claims against an employer for work-related injuries are generally limited to Workers Compensation claims. These laws, which are often referred to as “exclusive remedy” provisions, preclude a claimant from bringing a third-party lawsuit against an employer.

In Mr. Tooey’s case, Ferro/Oglebay convinced the Pennsylvania Superior Court that it was entitled to summary judgment based on Pennsylvania’s exclusive remedy law. The matter was appealed to the State’s Supreme Court where it was asserted that occupational injury claims stemming from latent diseases, such as asbestos cancer which doesn’t develop for at least 15 years after exposure, are exempt from Pennsylvania’s exclusive remedy statute as worded.

On November 22, 2013, the Pennsylvania Supreme Court issued its opinion in Tooey v. AK Steel Corp., et al., ruling 5-1 in favor of Mr. Tooey’s family. Specifically, the Supreme Court held that the exclusivity provision of the Pennsylvania Workers Compensation Act does not apply to third-party claims for diseases which manifest more than 300 weeks following the last occupational exposure. In the opinion, the court stated, "It is inconceivable that the legislature, in enacting a statute specifically designed to benefit employees, intended to leave a certain class of employees who have suffered the most serious of work-related injuries without any redress under the Act or at common law.”

The Supreme Court’s ruling allows the Tooey family’s case to now proceed against Ferro/Oglebay. The decision, which constitutes a major shift in Pennsylvania Law, will have more far-reaching effects. The case essentially paves the way for victims of latent occupational diseases, including but not limited to asbestos cancer/mesothelioma, to assert third-party claims against the former employers that put them “in harm’s way”.