The Punch Worthington Thoracic Surgery Research Laboratory

The David "Punch" Worthington Laboratory is located at the David Geffen School of Medicine at the UCLA Medical Center in Los Angeles, California. The Laboratory was made possible by a generous initial donation and continuing support from Roger G. Worthington. The Punch Worthington Lab is the home of exciting new research on novel strategies for the treatment of mesothelioma, lung cancer, leukemia, and other occupational cancers.

Roger Worthington is proud to help launch this vital research effort in honor of his father, Punch Worthington, Ph.D., who has asbestosis and lung cancer. Punch obtained a Ph.D. in Genetics but left a promising career in academia to pursue his true love: labor union organizing and advocacy.

Research at the Punch Worthington Lab is conducted by the Pacific Heart, Lung & Blood Institute ("PHLBI"), a non-profit medical research organization dedicated to finding cures for industrial-related diseases such as mesothelioma and lung cancer caused by asbestos and leukemia and myeloma caused by benzene. Roger G. Worthington is a founding donor and director of PHLBI.

 
Roger Worthington, Dr. Gerald Levey, the Dean of the UCLA Medical School, David "Punch" Worthington and Dr. Robert Cameron, Chief of Thoracic Surgery

PHLBI Research Plan

Under the direction of its Scientific Advisory Board, PHLBI has established an ambitious plan for conducting novel research in the diagnosis, treatment and prevention of mesothelioma and asbestos-related lung cancer and benzene-related hematologic cancers. PHLBI's research plan also includes investigation into much-needed administrative improvements in medical care that will provide patients with additional knowledge, security, and control regarding their treatment.

Mesothelioma and Asbestos-Related Lung Cancer

PHLBI is committed to being a worldwide leader in researching mesothelioma, a rare asbestos-related cancer that is uniformly fatal and in dire need of novel diagnostic, screening, staging, and treatment approaches. PHLBI's Robert Cameron, M.D. is Chief of Thoracic Surgery at The David Geffen School of Medicine at UCLA and has been at the forefront of developing innovative therapies for extending the lives of mesothelioma patients. PHLBI's research plan includes programs involving Immunotherapy, and Screening/Early Detection/Prevention.

Immunotherapy 
There is significant data and experience which indicates that mesothelioma may be successfully treated with manipulation of the immune system. Reports in the medical literature reveal success using immunotoxins and interferon. PHLBI plans to aggressively pursue the use of immune stimulating factors in the treatment of mesothelioma.

Immunotoxin Immunotherapy Projects 
Recent preliminary data indicates that a specific immunotoxin (interleukin-4 or "IL-4") has potent anti-cancer activity specifically in mesothelioma. PHLBIplans to explore combinations of the toxin with other treatments including chemotherapy, hyperthermia, and interferon therapy. This will be carried out in the laboratory using cells grown in culture. The ultimate goal is to apply this promising therapy in human patients in a clinical trial. This would require making enough of the toxin in a strict FDA-approved manner which would cost approximately $500,000 alone. Yet, if the findings in animal work are borne out by human administration, this toxin could be a key to significant progress toward a cure for this dreaded disease.

• Project #1: Immunotoxin combinations in vitro (budget need: $100K). This project will explore treatment combinations such as IL-4 immunotoxin with chemotherapy, hyperthermia, and interferon therapy conducted in the "Punch" Worthington Research Laboratory with mesothelioma cells grown in culture. The results of this project will guide further research to be conducted in animals (see Project #2 below).
• Project #2: Immunotoxin combinations in vivo (budget need: $250,000). This project will explore treatment combinations such as IL-4 immunotoxin with chemotherapy, hyperthermia, and interferon therapy conducted in the "Punch" Worthington Research Laboratory with mesothelioma cells injected into animals (mice). The results of this project will be used to guide further research to be conducted in humans (see Project #3 below).
• Project #3: Immunotoxin combinations in human clinical trials (budget need: $1,000,000). This project will explore treatment combinations such as IL-4 immunotoxin with chemotherapy, hyperthermia, and interferon therapy conducted at UCLA and other mesothelioma treatment centers across the country.

Interferon Immunotherapy Projects 
Interferon alpha has shown promising results in preliminary studies at UCLA and other clinical trials. The reasons are not clear but may involve a direct inhibitory effect on tumor cells, stimulation of the immune system and inhibition of blood vessel formation (angiogenesis). Interferons are normal messenger proteins that humans produce in response to viral infections and other specific infections such as tuberculosis. It is believed that they are also vital to the body's ability to fight abnormal cells like cancer cells. PHLBI plans to explore the use of interferons in the treatment of mesothelioma in both basic science experimentation and human clinical trials.

Screening/Early Detection/Prevention 
Populations of people exposed to asbestos, and therefore at risk for mesothelioma and lung cancer, currently have no way of determining whether they will develop one of these terrible cancers. Only approximately 15% of patients exposed to asbestos will actually develop mesothelioma or lung cancer. In addition, there is no test which can detect mesothelioma at an early or even pre-malignant stage. In order to help people at risk detect the disease at an early stage when there are many more options available for effective treatment, PHLBI plans an aggressive program for improving screening, early detection and prevention.

Screening Projects 
Breath test for volatile hydrocarbons (budget need: $150,000). In order for persons exposed to asbestos to determine whether they are among the smaller population of those who are at high risk of actually developing asbestos-related malignancies, PHLBI plans to examine the volatile hydrocarbons which are exhaled in people's breath (breath testing). Dr. Cameron has already gained significant experience in breath testing of patients with lung cancer and is eager to expand the testing to patients exposed to asbestos and at risk for mesothelioma. The test involves breathing into a tube which collects volatile hydrocarbons on a filter so they can be analyzed. This project will be conducted at UCLA and other mesothelioma treatment centers across the country.

Early Detection Projects 
Proteonomics in early detection of mesothelioma (budget need: $500,000). Normal and abnormal cells in the body generate distinctive amounts and kinds of proteins. This "protein profile" can be used much like a fingerprint. PHLBI plans to conduct investigation to determine the "protein profile" generated by mesothelioma cells so that simple blood tests can be used to detect mesothelioma at an early stage. This project will involve analysis of blood and urine from mesothelioma victims at all stages of disease as well as normal and asbestos-exposed people to better define protein profiles in these populations. This project will be conducted at UCLA and other mesothelioma treatment centers across the country.

Prevention Projects 
COX-2 inhibition as prevention of mesothelioma (budget need: $1,500,000). Chronic inflammation induced by asbestos fibers has been implicated in the development of mesothelioma. One way to prevent the development of mesothelioma in patients with known significant asbestos exposure is to treat them with COX-2 inhibitors (Celebrex, etc.) of inflammation. This has already been shown to prevent other cancers, such as colon cancer, and may be effective in lung cancer. This project will be conducted at UCLA and other mesothelioma treatment centers across the country in conjunction with Unions of high risk workers/patients.

Hematologic Cancers

PHLBI also has an ambitious plan for researching advancements in the diagnosis and treatment of hematologic cancers such as acute myelogenous leukemia, multiple myeloma and non-Hodgkin's lymphoma. These particular cancers have been related to exposure to benzene. PHLBI's Gary Schiller, M.D. is Chief of Hematology-Oncology at The David Geffen School of Medicine at UCLA and has conducted numerous studies which put into clinical trials new drugs and therapeutics which are developed in the laboratory for treatment of acute myelogenous leukemia ("AML") and other hematologic malignancies.

Bone Marrow Models 
Ex vivo bone marrow models (budget need: $1,500,000). There is a desperate need for a laboratory system for studying bone marrow models in AML and other hematologic cancers. PHLBI intends to develop a laboratory model of bone marrow diseases using tissue engineering techniques. There has been preliminary work in this area conducted by PHLBI personnel and the results have been encouraging. This type of work can lead to additional applications involving almost every facet of hematopoiesis (bone marrow growth and maturation), including red blood cell formation and development, platelet formation, and white blood cell formation. This knowledge will lead to improved treatments for AML, anemia, low platelets, bone marrow transplantation, and even certain infections.

Administrative Improvements in Medical Care

In addition to its research into therapeutic and scientific advancements, PHLBI is committed to investigating ways in which the administration of medical care can be improved so that patients are vested with additional knowledge, security and control regarding their treatment.

Electronic Medical Records System 
(Budget need: $500,000). PHLBI believes in empowering patients with their own medical records for better understanding and control over their own health and treatment. PHLBI supports an electronic medical records system, which is directly accessible to patients. Such a system would enable data to be directly entered from point of generation and allow for the coordinated transfer of medical information among providers and research studies. This type of system would result in complete and organized records possessed by all persons and facilities involved in the treatment, thereby increasing the time for meaningful discussions of medical problems between health care providers and patients and improving the quality and efficacy of patient care.

Health Care Systems 
(Budget need: $1,000,000). PHLBI recognizes the need for development of novel methods of health care delivery. PHLBI supports a system founded on an "ability to pay" basis. This means that instead of every person paying a health-handicapped insurance premium to a "for-profit" company, people would pay based on their ability to contribute to a "catastrophic" government fund while using individual savings accounts for lower cost items. This would allow individual provider-based pricing but income-based premium payments. This project will involve collection and analysis of data on individual access and consistency of access system approach.

 
Roger Worthington, Dave "Punch" Worthington and David Worthington

 
David "Punch" Worthington, Dr. Gerald Levey, the Dean of the UCLA Medical School, Dr. Robert Cameron, Chief of Thoracic Surgery and Dr. Mary Maish, Thoracic Surgeon