Paradigm shift: Switch for programmed cell death promotes spread of glioblastomaMarch 12, 2008Malignant tumors have usually lost their ability to destroy themselves by programmed cell death, or apoptosis. Therefore, tumors are often resistant to chemotherapy or radiation therapy, whose effect is based on forcing tumor cells to commit suicide. This resistance to apoptosis is caused by defects in one of the numerous molecular switches regulating the self-destruction process. This is why scientists have been trying for a long time to restore the formation of these switches in cancer cells and, thereby, to restore their apoptotic ability. Among the key molecular switches is cell surface protein CD95, which is activated by the binding of its partner, CD95L. This triggers a whole cascade of biochemical signals leading to the death of the cell. At the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Dr. Ana Martin-Villalba and her team have been studying the function of CD95 on glioblastoma cells. Glioblastoma is an extremely aggressive malignant brain tumor that resists all treatments. The cancer grows like a coral and invades surrounding brain tissue with very fine protrusions. Individual, isolated tumor cells can penetrate even further. Thus, surgeons have no chance to completely remove the tumor tissue. In addition, glioblastoma is highly resistant to both chemotherapy and radiotherapy.
Martin-Villalba's team found large amounts of CD95 on glioblastoma cells, while CD95L was localized primarily at the so-called invasive front - the border between tumor tissue and healthy brain tissue. Despite the presence of both molecules, the cells are resistant to programmed cell death. But this is not all: If CD95 on the surface of glioblastoma cells is activated by CD95L, this leads to the production of a protein called MMP9, which is known to be a molecular scissors. MMP9 cuts through the network of interwoven protein fibers that separate different tissue layers of the body from each other. With the aid of these protein scissors, tumor cells invade healthy tissue and form the dangerous protrusions that penetrate deep into the brain tissue. The result showed the scientists a way how to stop the invasion of glioblastoma: They treated mice that had been transplanted glioblastoma with an antibody that blocks CD95. As a result, the migration of cancer cells ceded. "This is almost a paradigm shift," says Ana Martin-Villalba. "Up to now, the goal has been to promote formation of CD95 and CD95L in tumor cells. In the case of glioblastoma, we now have to warn against this approach: This would only additionally support the spread of the tumor. The goal is rather to block activation of CD95." However, it is currently not possible to investigate this treatment approach in humans, because a useable antibody against human CD95 protein is not yet available. Helmholtz Association of German Research Centres | |||||||||||||||||||||
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Related Glioblastoma Current Events and Glioblastoma News Articles New approach to gene therapy may shrink brain tumors, prevent their spread Massachusetts General Hospital (MGH) researchers are investigating a new approach to gene therapy for brain tumors - delivering a cancer-fighting gene to normal brain tissue around the tumor to keep it from spreading. Drugs to inhibit blood vessel growth show promise in rat model of deadly brain tumor In a landmark study, Medical College of Wisconsin researchers in Milwaukee report that drugs used to inhibit a specific fatty acid in rat brains with glioblastoma-like tumors not only reduced new blood vessel growth and tumor size dramatically, but also prolonged survival. The study is the featured cover story of the August, 2008 Journal of Cerebral Blood Flow & Metabolism. Vitamin C injections slow tumor growth in mice High-dose injections of vitamin C, also known as ascorbate or ascorbic acid, reduced tumor weight and growth rate by about 50 percent in mouse models of brain, ovarian, and pancreatic cancers, researchers from the National Institutes of Health (NIH) report in the August 5, 2008, issue of the Proceedings of the National Academy of Sciences. Cancer-killing viruses influence tumor blood-vessel growth Viruses genetically designed to kill cancer cells offer a promising strategy for treating incurable brain tumors such as glioblastoma, but the body's natural defenses often eliminate the viruses before they can eliminate the tumor. Study: Patients 75 years and older with brain tumors may benefit from more aggressive treatment A new study from University Hospitals Case Medical Center (UHCMC) finds that elderly patients - 75 years old and older-- with malignant brain tumors are not treated as aggressively as patients between 65 and 75 years old. NovoCure presents results from breast cancer pilot study NovoCure announced today that it presented the results from a single-arm pilot trial evaluating the Novo-TTF, a non-invasive portable medical device, combined with neo-adjuvant chemotherapy for the treatment of patients with locally advanced breast cancer. MRI: A window to genetic properties of brain tumors Doctors diagnose and prescribe treatment for brain tumors by studying, under a microscope, tumor tissue and cell samples obtained through invasive biopsy or surgery. Pharmaceutical market fails pregnant women; and more In a clinical trial published this week in PLoS Medicine, Charles Sawyers and colleagues looked at the safety of a drug called rapamycin in a selected group of patients who were undergoingsurgery after recurrence of glioblastoma (a highly malignant tumor of the brain). Combined radiation seed, chemotherapy wafer implants show promise in treating cancerous brain tumors In the battle against malignant brain tumors, dual implantation of radioactive seeds and chemotherapy wafers following surgery showed promising results in a study led by specialists at the Neuroscience Institute at the University of Cincinnati (UC) and University Hospital. Novel anticancer strategy moves from laboratory to clinic Researchers at Emory University have developed a novel anti-tumor compound that represents a distinct strategy: targeting one of the most important "intercept points" for cancer cells. More Glioblastoma Current Events and Glioblastoma News Articles |
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