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Researchers identify genes that allow brain cancer-causing stem cells to resist treatment
December 18, 2006While great interest has followed the discovery of neural stem cells and their potential for someday treating diseases and injuries of the brain and spinal cord, recent research identified "cancer stem cells," a small population of cells that appear to be the source of cells comprising a malignant brain tumor. Theoretically, if these mother cells can be destroyed, the tumor will not be able to sustain itself. On the other hand, if these cells are not removed or destroyed, the tumor will continue to return despite the use of current cancer-killing therapies.
Researchers at Cedars-Sinai Medical Center's Maxine Dunitz Neurosurgical Institute, who first isolated cancer stem cells in adult brain tumors in 2004, have now found these cells to be highly resistant to chemotherapy and other treatments. Even if a tumor is almost completely obliterated, it will regenerate from the surviving cancer stem cells and be even more resistant to treatment than before.
Results of studies on three established glioma cell lines and tumor tissue removed from five patients at Cedars-Sinai appear in the Dec. 2 issue of the journal Molecular Cancer. The researchers describe genes and mechanisms that give cancer stem cells their chemoresistant properties. They also allude to ongoing research aimed at developing methods for readily distinguishing cancer stem cells from normal neural stem cells, which could lead to therapies targeting the cancer-causing cells without damaging healthy ones.
"If one believes in the cancer stem cell hypothesis, this is an extremely important area of investigation. These stem cells are like the mother cells of the tumor, which I think is a very significant observation. It may guide the way we research tumors and the way we look for therapeutic approaches to treat these tumors because all of our efforts will need to be directed at killing these cells," said Keith L. Black, M.D., neurosurgeon, director of the Maxine Dunitz Neurosurgical Institute and chair of Cedars-Sinai's Department of Neurosurgery.
Cancer stem cells were first found in certain leukemias and in breast carcinomas. In 2004, shortly after cancer stem cells were identified in pediatric brain tumors, researchers at Cedars-Sinai's Institute reported the first isolation of cancer stem cells in adult brain tumors.
"Gliomas that are treated with chemotherapy recur with renewed resilience and aggression. Although the drugs kill most of the cells in the tumor, cancer stem cells may be left behind. In this study, we provide the first evidence that cancer stem cells have a significant resistance to conventional chemotherapeutic agents. We also link this resistance to genes that are known to inhibit a cell death process called apoptosis," said neurosurgeon John S. Yu, M.D., co-director of the Comprehensive Brain Tumor Program at Cedars-Sinai and senior author of the journal article.
Normal stem cells are "immature" cells that have the potential to become any of several types of cells. Cancer stem cells have the same multi-potent and self-renewing properties, but instead of producing healthy cells, they propagate cancer cells.
Part of the study included a comparison of cells taken from patients' primary (first-onset) tumors with cells taken from recurring tumor after radiation, chemotherapy and/or immunotherapy. In each of the five cases examined, the recurrent tumors contained much higher concentrations of cancer stem cells, indicating that while many tumor cells may have died, treatment-resistant "source" cells survived and regenerated.
Another finding suggests that cancer stem cells are responsible not only for regeneration of tumor cells but also encourage their migration. Gliomas are extremely difficult to treat because they evade treatment and because they are highly invasive.
"The identification and study of brain cancer stem cells is providing insight into the way tumors form and grow," said Yu. "This may be a major step toward designing therapies that use brain cancer stem cells as a target, not only to destroy a tumor but to prevent it from coming back."
Cedars-Sinai Medical Center
"If one believes in the cancer stem cell hypothesis, this is an extremely important area of investigation. These stem cells are like the mother cells of the tumor, which I think is a very significant observation. It may guide the way we research tumors and the way we look for therapeutic approaches to treat these tumors because all of our efforts will need to be directed at killing these cells," said Keith L. Black, M.D., neurosurgeon, director of the Maxine Dunitz Neurosurgical Institute and chair of Cedars-Sinai's Department of Neurosurgery.
Cancer stem cells were first found in certain leukemias and in breast carcinomas. In 2004, shortly after cancer stem cells were identified in pediatric brain tumors, researchers at Cedars-Sinai's Institute reported the first isolation of cancer stem cells in adult brain tumors.
"Gliomas that are treated with chemotherapy recur with renewed resilience and aggression. Although the drugs kill most of the cells in the tumor, cancer stem cells may be left behind. In this study, we provide the first evidence that cancer stem cells have a significant resistance to conventional chemotherapeutic agents. We also link this resistance to genes that are known to inhibit a cell death process called apoptosis," said neurosurgeon John S. Yu, M.D., co-director of the Comprehensive Brain Tumor Program at Cedars-Sinai and senior author of the journal article.
Normal stem cells are "immature" cells that have the potential to become any of several types of cells. Cancer stem cells have the same multi-potent and self-renewing properties, but instead of producing healthy cells, they propagate cancer cells.
Part of the study included a comparison of cells taken from patients' primary (first-onset) tumors with cells taken from recurring tumor after radiation, chemotherapy and/or immunotherapy. In each of the five cases examined, the recurrent tumors contained much higher concentrations of cancer stem cells, indicating that while many tumor cells may have died, treatment-resistant "source" cells survived and regenerated.
Another finding suggests that cancer stem cells are responsible not only for regeneration of tumor cells but also encourage their migration. Gliomas are extremely difficult to treat because they evade treatment and because they are highly invasive.
"The identification and study of brain cancer stem cells is providing insight into the way tumors form and grow," said Yu. "This may be a major step toward designing therapies that use brain cancer stem cells as a target, not only to destroy a tumor but to prevent it from coming back."
Cedars-Sinai Medical Center
Stem Cell Current Events and Stem Cell News RSSGene mismatch influences success of bone marrow transplants
A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics.
New research shows versatility of amniotic fluid stem cells
For the first time, scientists have demonstrated that stem cells found in amniotic fluid meet an important test of potential to become specialized cell types, which suggests they may be useful for treating a wider array of diseases and conditions than scientists originally thought.
First reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
Researchers find potential treatment for Huntington's disease
Investigators at Burnham Institute for Medical Research (Burnham), the University of British Columbia's Centre for Molecular Medicine and Therapeutics and the University of California, San Diego have found that normal synaptic activity in nerve cells (the electrical activity in the brain that allows nerve cells to communicate with one another) protects the brain from the misfolded proteins associated with Huntington's disease.
Researchers 'notch' a victory toward new kind of cancer drug
Scientists have devised an innovative way to disarm a key protein considered to be "undruggable," meaning that all previous efforts to develop a drug against it have failed.
UCI embryonic stem cell therapy restores walking ability in rats with neck injuries
The first human embryonic stem cell treatment approved by the FDA for human testing has been shown to restore limb function in rats with neck spinal cord injuries - a finding that could expand the clinical trial to include people with cervical damage.
First use of antibody and stem cell transplantation to successfully treat advanced leukemia
For the first time, researchers at Fred Hutchinson Cancer Research Center have reported the use of a radiolabeled antibody to deliver targeted doses of radiation, followed by a stem cell transplant, to successfully treat a group of leukemia and pre-leukemia patients for whom there previously had been no other curative treatment options.
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.
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