PMC Research Update:
PMC research scientists Drs. Raymond Wong and Irina Ianculescu are currently developing a novel experimental system that holds promise for improved modeling of human pleural mesothelioma tumors in tissue culture plates. This system mimics the complex 3-dimensional structure of solid tumors without using research animals, which is becoming less acceptable in medical research. By using this model, they are investigating the unique gene expression profiles of human pleural mesothelioma cells, i.e., the abnormal increase or decrease of genetic signals in cancerous cells versus normal cells. By studying these highly regulated signals, we hope to gain further insight into the specific genetic changes that lead to mesothelioma and its frequent resistance to radiation and chemotherapy. This information may allow us to elucidate a particular genetic signature of pleural mesothelioma, allowing for identification of individuals who are at high risk for developing this dreadful disease. 3-dimensional culture models of human pleural mesothelioma will also be useful for optimizing novel therapies, such as cryotherapy and immunotherapy.
PMC is also continuing to work in collaboration with the University of Pittsburgh, University of Pennsylvania, Mt. Sinai, New York University, and the Heat and Frost Insulators Union to establish a west coast repository of high quality, asbestos-related tumor tissue specimens and fluid samples from pleural mesothelioma patients. This repository will be used to catalyze research into developing new diagnostic tests for earlier detection of the disease.
At the UCLA Department of Bioengineering, Drs. Warren Grundfest and Marko Kostic are continuing to develop a prototype cryosprayer designed to safely deliver liquid nitrogen into the chest cavity of mesothelioma patients undergoing surgery. This initiative is based on data recently presented by Drs. Robert Cameron and Dongmei Hou of the UCLA Punch Worthington laboratory, where they demonstrated that human pleural mesothelioma cells are particularly sensitive to freezing. Using liquid nitrogen to carefully freeze a thin portion of the chest wall surface after surgically removing all visible mesothelioma tumors may potentially destroy residual tumor cells, thereby reducing the chance of disease recurrence in patients.
UCLA Bioengineering Research Update:
Cryotherapy System-The Biophotonics Laboratory in the Department of Bioengineering, directed by Professor Warren S. Grundfest, M.D., FACS, at the UCLA School of Engineering is continuing development of a novel cryotherapy system for intraoperative treatment of mesothelioma. This project is based on the work by Dr. Robert B. Cameron at the Pacific Meso Center which has shown that mesothelioma cancer cells are sensitive to cold. The research in Biophotonics laboratory explores the potential use of liquid nitrogen as means to reduce or eliminate the remaining cancer cells that cause recurrence of mesothelioma after the resection. More information will be shared at the 3rd International Symposium.
The researchers have developed initial computer models that predicted depth and temperature of freezing during therapy. Presently, researchers are working on expanding computer simulations to include more complex anatomical and physiological models. These new simulations will enable better understanding of the impact that blood flow and bone have on the temperature profile of tissue, as well as how different blood flow rates and liquid nitrogen treatment times affect the tissue temperature. Work on developing algorithms for the optimal dose of liquid nitrogen is also continuing.
This extramural grant has been funded by Pacific Meso has also enabled UCLA to progress in developing a novel cryo sprayer system. After conducting several bench top tests of the system, an improved liquid nitrogen dispensing module was designed and fabricated. Currently, engineers are designing a distal end that will accommodate the new module and additional tests are planned for the very near future.
PMC Research Update
Scientists at the Pacific Meso Center (PMC) are developing novel methods for creating and studying mesothelioma tumors outside of the human body, in order to more efficiently and accurately test the effectiveness of promising new treatments. By combining human mesothelioma cells, connective tissue (stroma), and immune cells in culture dishes, our researchers can create small, nodule-like structures called “spheroids.” These spheroids appear nearly identical to the mesothelioma nodules that typically are found on the lining of the chest cavity in patients with this disease. Many potential therapies, including immunotherapy and others, are so complex that the optimal conditions necessary for successful therapy cannot be defined easily, but require testing literally hundreds of different conditions – something that is not possible in standard research models. Our tumor spheroid model now makes such testing possible; consequently speeding the translation of basic research into clinical therapy for mesothelioma patients.
PMC scientists also are beginning to study gene expression in mesothelioma cells; that is, the extent to which certain genetic signals are abnormally increased or decreased compared to normal cells. Cell growth and death is highly regulated by genetic signals, and a better understanding of the specific genetic changes that occur in mesothelioma cells will give us insight into what causes these cells to grow and divide uncontrollably. Furthermore, the specific genes involved may provide a characteristic genetic profile or signature, which may be used to identify individuals who are at particularly high risk for developing mesothelioma even years before it occurs. Such knowledge would allow treatments to be tested that potentially could prevent the disease altogether.
UCLA Bioengineering Research Update:
The Biophotonics Laboratory in the Department of Bioengineering, directed by Professor Warren S. Grundfest, M.D., FACS, at the UCLA School of Engineering continues to develop a unique tool to aid in the treatment of Mesothelioma. This research effort takes advantage of the fact that mesothelioma is sensitive to freezing. Work by Dr. Robert B. Cameron and others has shown that freezing can successfully treat local chest wall mesothelioma recurrences. But to date there has been no practical instrumentation to apply this technology at the time of resection of primary tumors.
Work in the Biophotonics laboratory is developing instrumentation to effectively apply the cryogenic coolant (liquid nitrogen) to freeze mesothelioma. Additional studies are developing algorithms to determine the optimal dose of liquid nitrogen. This technology will be applied in an effort to reduce mesothelioma recurrence after primary resection in the hope that the freezing technique will help kill residual mesothelioma cells.
Funding from the Pacific Meso has also enabled engineers and scientists at UCLA to work on the development of computer models which predict the depth and temperature of freezing during therapy. Validation of these computer models is the subject of current research. Eric Jung, undergraduate mechanical engineering student, and James Garritano, graduate Bioengineering student, have joined the project to work with these sophisticated computer tools.
UCLA Bioengineering Research Update:
The Biophotonics Laboratory in the Department of Bioengineering, directed by Professor Warren S. Grundfest, M.D., FACS, at the UCLA School of Engineering has initiated the development of a unique tool to aid in the treatment of Mesothelioma. This tool uses cryogenic fluid chilled to -196ºC to rapidly freeze mesothelioma cells that remain after surgical resection or when they occur as superficial recurrences on the chest wall. Investigations will focus on the use of this cryo therapy technology to reduce or eliminate the cancer cells in effort to prolong life. The support from the Pacific Meso Foundation has allowed Dr. Grundfest to acquire and build a uniquely designed instrument called a CryoSprayer that allows for controlled delivery of a cryogenic fluid during surgery or during treatment for post-surgical superficial chest wall occurrences. Liquid nitrogen serves as a cryogenic fluid because it rapidly freezes the surface and then evaporates producing a thin layer of frozen tissue. Protecting the vital structures but ensuring the complete treatment of lesions is necessary before clinical trials can begin.
Funding from Pacific Meso has also enabled engineers and scientists at UCLA to work on the development of computer models which predict the depth and temperature of freezing during therapy. Validation of these computer models is the subject of current research. An additional UCLA graduate student and an undergraduate student have joined the project to work with these sophisticated computer tools.
PMC Research Update:
We recently launched a 3-dimensional in vitro (cultures in petri dishes) tumor model (3DTM) program for better assessment of potential mesothelioma therapies. Evidence is mounting that these 3DTM’s more accurately reflect the complex tumor microenvironment in vivo (in animals/people) than traditional 2-dimensional “monolayer” culture models. This is particularly true with respect to gene expression, signaling pathways, cellular metabolism, and drug sensitivity. 3DTM will allow for more rapid and cost-effective testing of potential anti-tumor agents, including immunotoxins, cytokines, chemokines, gene-modified stromal cells, and anti-angiogenic compounds. Such improvement in testing candidate compounds promises to provide quicker “proof-of-concept” data and lead to earlier clinical trials for mesothelioma patients.
PMC also in on the verge of launching its mesothelioma screening project. This program will evaluate a variety of tests designed to identify individuals who have been exposed to asbestos and specifically those who are at risk for developing mesothelioma. Identification of people likely to develop this fatal disease would allow prophylactic pleural-ablative interventions to be used to prevent the disease altogether.
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