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Gene therapy may protect normal tissues during radiation retreatment for lung cancer
October 17, 2005Gene therapy could be used as an agent to protect normal tissues, including the esophagus and lung, from damage during a second administration of radiation therapy for non-small cell lung cancer, according to an animal study presented today by University of Pittsburgh researchers at the 47th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO) in Denver.
"A major challenge in treating lung tumors with radiation is the toxicity of radiation to healthy tissue," said Joel S. Greenberger, M.D., professor, University of Pittsburgh School of Medicine. "This can result in major quality-of-life issues for lung cancer patients receiving radiation therapy for their diseases. In previous studies, we demonstrated that gene therapy may protect healthy tissues from damage prior to an initial course of radiation therapy. In this study, we found that gene therapy also can protect the same healthy tissue during retreatment with radiation." Dr. Greenberger explained that a related study shows the effectiveness of aerosol delivery of this therapy by an inhalation nebulizer making it clinically feasible.
In the study, animal models were used to test the protective effects of manganese superoxide dismutase plasmid liposome (MnSOD-PL) gene therapy during exposure to radiation. One group of mice received an intratracheal injection of MnSOD-PL 24 hours before a course of 14 Gy irradiation, while a second group received 14 Gy irradiation alone. The mice were observed for six months for any toxic pulmonary effects and then subdivided into two more groups. One of these groups was exposed to a second lung irradiation of 10 Gy without MnSOD-PL and the other received an injection of MnSOD-PL 24 hours prior to radiation exposure.
The researchers found that in mice that received the initial 14 Gy dose there was 50 percent survival at 180 days (due to lung toxicity) compared to 87.5 percent survival during the same length of time for mice that were injected with MnSOD-PL prior to irradiation. Mice that received MnSOD-PL before both the 14 Gy dose as well as the subsequent 10 Gy dose had the best survival rate overall. Mice treated with MnSOD-PL before the first dose of radiation had a survival rate of 31.6 percent, while mice receiving the treatment before both courses of radiation had a survival rate of 47.6 percent.
"Administration of this type of gene therapy appeared to prevent the damaging effects of radiation, even when the radiation was re-administered after six months," said Dr. Greenberger. "Future studies will tell us whether this therapy can improve the quality of life for lung cancer patients and help us more effectively treat lung cancer without the damaging side effects."
Lung cancer is the leading cause of cancer-related death in men and women. In 2005, more than 170,000 new cases of lung cancer will be diagnosed. Side effects from radiation therapy for lung cancer can include fatigue, skin changes, swelling of the esophagus, hair loss in the treated area, dry cough caused by swelling of the lung tissue and sore throat.
University of Pittsburgh Medical Center
The researchers found that in mice that received the initial 14 Gy dose there was 50 percent survival at 180 days (due to lung toxicity) compared to 87.5 percent survival during the same length of time for mice that were injected with MnSOD-PL prior to irradiation. Mice that received MnSOD-PL before both the 14 Gy dose as well as the subsequent 10 Gy dose had the best survival rate overall. Mice treated with MnSOD-PL before the first dose of radiation had a survival rate of 31.6 percent, while mice receiving the treatment before both courses of radiation had a survival rate of 47.6 percent.
"Administration of this type of gene therapy appeared to prevent the damaging effects of radiation, even when the radiation was re-administered after six months," said Dr. Greenberger. "Future studies will tell us whether this therapy can improve the quality of life for lung cancer patients and help us more effectively treat lung cancer without the damaging side effects."
Lung cancer is the leading cause of cancer-related death in men and women. In 2005, more than 170,000 new cases of lung cancer will be diagnosed. Side effects from radiation therapy for lung cancer can include fatigue, skin changes, swelling of the esophagus, hair loss in the treated area, dry cough caused by swelling of the lung tissue and sore throat.
University of Pittsburgh Medical Center
Gene Therapy Current Events and Gene Therapy News RSSResearch reveals lipids' unexpected role in triggering death of brain cells
The lipid that accumulates in brain cells of individuals with an inherited enzyme disorder also drives the cell death that is a hallmark of the disease, according to new research led by St. Jude Children's Research Hospital investigators.
No-entry zones for AIDS virus
The AIDS virus inserts its genetic material into the genome of the infected cell. Scientists of the German Cancer Research Center have now shown for the first time that the virus almost entirely spares particular sites in the human genetic material in this process. This finding may be useful for developing new, specific AIDS drugs.
Cornell researchers identify a weak link in cancer cell armor
The seeming invincibility of cancerous tumors may be crumbling, thanks to a promising new gene therapy that eliminates the ability of certain cells to repair themselves.
Treatment to improve degenerating muscle gains strength
A study appearing in Science Translational Medicine puts scientists one step closer to clinical trials to test a gene delivery strategy to improve muscle mass and function in patients with certain degenerative muscle disorders.
Iowa State University researcher discovers key to vital DNA, protein interaction
A researcher at Iowa State University has discovered how a group of proteins from plant pathogenic bacteria interact with DNA in the plant cell, opening up the possibility for what the scientist calls a "cascade of advances."
Scientists successfully reprogram blood cells
Researchers have transplanted genetically modified hematopoietic stem cells into mice so that their developing red blood cells produce a critical lysosomal enzyme -preventing or reducing organ and central nervous system damage from the often-fatal genetic disorder Hurler's syndrome.
Immune therapy can protect against or treat later lymphoma
Specially developed immune system cells that target the common Epstein-Barr virus can protect immune-suppressed bone marrow transplant recipients against lymph system disease and cancers that arise from the viral infection.
Caltech researchers show efficacy of gene therapy in mouse models of Huntington's disease
Researchers at the California Institute of Technology (Caltech) have shown that a highly specific intrabody (an antibody fragment that works against a target inside a cell) is capable of stalling the development of Huntington's disease in a variety of mouse models.
Immunotherapy demonstrates long-term success in treating lymphoma
Targeted immunotherapy has been an attractive new therapeutic area for a number of cancers because it has the potential to destroy tumor cells without damaging surrounding normal tissue. New study results demonstrate high success rates using specialized white blood cells to prevent or treat lymphoma associated with the Epstein-Barr virus (EBV-lymphoma) in patients who have received a hematopoietic stem cell transplant (HSCT).
Toward bold new anti-cancer medicines
Bold new strategies in the battle against cancer may turn forms of the disease that presently are incurable into manageable conditions that can be controlled for long periods of time.
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