Summer 2005 Drug prolongs lung cancer survival Reducing rejection in transplant Killer molecule identified Dynamic duo in heart disease
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New Research Breakthroughs at UHN
Drug prolongs lung cancer survival in study led by UHN researcher A National Cancer Institute of Canada Clinical Trials Group study, led by Dr. Frances Shepherd (OCI/PMH) in collaboration with Dr. Andrea Bezjak (OCI/PMH) and 17 other researchers from eight different countries, showed that erlotinib—a drug that curbs cells from growing and multiplying—can prolong survival for some non-small cell lung cancer (NSCLC) patients who have been treated previously. N Engl J Med. 2005 Jul 14;353(2):123-32. [PubMed abstract] A team of researchers at TGRI/TGH, including Drs. David Grant, Gary Levy, Reginald Gorczynski, M. James Phillips and Tom Waddell, have discovered that removing Fgl-2 from organs reduces the rejection that typically takes place in xenotransplantation—the transfer of organs from one species to another species. Many central nervous system disorders involve inflammation, a process that is orchestrated by microglia. Thus there is considerable interest in anti-inflammatory strategies that target microglia. Microglia wreak their destruction by producing oxygen free radicals—a dangerously reactive form of oxygen. Research by Zamaneh Kassiri, a post-doctoral fellow in Dr. Rama Khokha's lab (OCI/PMH), in collaboration with Drs. Gavin Oudit, Peter Backx and Peter Liu (TGRI/TGH), has provided some key clues into why the heart becomes enlarged in heart disease patients. In a mouse model of heart failure, the researchers blocked two molecules—matrix metalloproteinases (which regulate the structures that support tissues) and TNFalpha (which is elevated in patients with heart disease)—completely preventing heart enlargement in these mice. These researchers further established a novel connection between the two pathways through a physiological inhibitor of metalloproteinase called TIMP-3. Circ Res. 2005 Jul 21; [Epub ahead of print] [PubMed abstract]
The study, evaluating 731 patients, showed that there was a 42.5 percent improvement in the average survival of patients who were treated with erlotinib compared to patients who were given a placebo. The patients who received erlotinib also had an improved quality of life: their symptoms of pain, shortness of breath and cough were decreased, and their physical function was significantly better.
“Lung cancer is the leading cause of cancer death among men and women in North America,” says Dr. Shepherd. “Once NSCLC patients have been given one or two rounds of chemotherapy their treatment options become limited. This drug now offers a new alternative for patients who previously had no other options for therapy.”
Research supported in part by a grant from OSI Pharmaceuticals to the National Cancer Institute of Canada Clinical Trials Group.
Institute: OCI/PMH
Division: Clinical Studies Resource Centre
Researchers reduce rejection by removing molecule
Transplanting mice hearts with and without Fgl-2—a molecule that is involved in blood clotting—into rats showed that the immune response of the rats was decreased when the mice hearts lacked Fgl-2. They also determined that the reduced rejection was easier to treat—using drugs that are already available for use in humans—than the standard rejection.
“Xenotransplantation could potentially alleviate the existing organ shortage by providing an unlimited supply of organs,” says Dr. Grant. “These initial findings suggest that if patients could be given transplants that lacked Fgl-2, they could be more easily treated.”
Research supported by the Canadian Institute of Health Research and Heart and Stroke Foundation of Canada
Institute: TGRI/TGH
Division: Cellular & Molecular Biology
UHN researchers identify a killer molecule in immune cells
Dr. Lyanne Schlichter's lab has shown that a gate on the surface of microglia called Kv1.3 allows these immune cells of the brain to kill neurons following brain injury and in disease states.
“This discovery offers a new strategy for controlling microglia and hence reduce neuronal death,” says Dr. Schlichter. "We are now testing drugs that inhibit Kv1.3 in animal models for stroke and neurotrauma.“
J Neurosci. 2005 Aug 3;25(31):7139-49 [PubMed abstract]
Research supported by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada
Institute: TWRI/TWH
Division: Cell & Molecular Biology
Eliminating a dynamic duo may provide new treatment for heart disease
Research supported by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, National Science Foundation and National Institutes of Health.
Institutes: OCI/PMH and TGRI/TGH
Divisions: Experimental Therapeutics, Cell & Molecular Biology, Signaling Biology
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UHN Researcher Named to Canada Research Chair
UHN Research extends its congratulations to Dr. Gary Lewis (TGRI/TGH) who was awarded a renewal of his Tier II Canada Research Chair in Vascular and Metabolic Biology. With it, he will continue his groundbreaking research on insulin resistance and its relationship to cardiovascular disease.
| Research Fact |
In the July 2005 issue of Scientific American, Dr. Andres Lozano and recent PhD graduate Suneil Kalia (TWRI/TWH) reviewed the emerging genetic and cellular discoveries in the area of Parkinson disease.
A message from your editors
This issue of Net Results EXPRESS replaces the July and August issues. Net Results EXPRESS will resume its regular monthly schedule in September, 2005.