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Ireland Cancer Center researchers advance stem cell gene therapy
December 13, 2007Researchers present findings at American Society of Hematology Meeting
Ireland Cancer Center of University Hospitals Case Medical Center researchers have recently made great strides in stem cell gene therapy research by transferring a new gene to cancer patients, via their own stem cells, with the ultimate goal of being able to use stronger chemotherapy treatment with less severe side effects. Under this protocol, MGMT, a drug-resistance gene, is added into purified hematopoietic stem cells to protect these cells from the damage of chemotherapy regimens.
In one of 24 presentations by Ireland Cancer Center researchers at the annual American Society of Hematology meeting, Stanton Gerson, MD, and colleagues presented that eight patients were enrolled on the trial and six were infused with their own stem cells which were engineered to carry the MGMT gene. In three patients, stem cells carrying the gene were identified in their blood or bone marrow. In one patient, stem cells carrying the gene were detected up to 28 weeks after their administration. This significant finding has never been reported before with this gene and drug combination.
¡§This study is the first to show the success of treatment with evidence that stem cells now carry the new gene,¡® says Dr. Gerson, Director of the Ireland Cancer Center and Case Comprehensive Cancer Center, who spearheaded the Phase I study along with a team of researchers. ¡§These patients show the success of treatment with evidence that their stem cells now carry the new genes. This is a breakthrough ¡V the first time selection with MGMT has been shown to occur in patients.¡®
Preclinical animal research, conducted by Dr. Gerson and his colleagues, has shown that the gene G156A-MGMT can provide stem cells with very high levels of drug resistance, compared to normal stem cells not carrying the gene. In the Phase I trial for patients with advanced malignancies, researchers collected peripheral blood stem cells from patients and exposed them to a retrovirus containing the G156A-MGMT gene.
In addition to this promising research, Ireland Cancer Center scientists presented 24 oral and poster presentations at ASH. ¡§The breadth and depth of this innovative hematologic research at the Ireland Cancer Center are outstanding,¡® says Alvin Schmaier, MD, Chief of Hematology/Oncology at UHCMC and Case Western Reserve University School of Medicine. ¡§Our faculty is making tremendous advances in these fields which is reflected in their being chosen for oral and poster presentations.¡®
The presentations include:
* Dr. Hillard Lazarus and colleagues presented significant findings that treatment with Rituximab before transplantation results in cure rate and overall survival in patients undergoing autologous stem cell transplantation for Diffuse Large B-Cell lymphoma.
* Dr. Lazarus and colleagues of the Eastern Cooperative Oncology Group (ECOG) presented data that show that Imatninib (Gleevec) does not change outcomes on patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia.
* Dr. Lazarus presented an assessment of data over 30 years regarding acute leukemia and its management. He found that all avenues lead to stem cell transplantations. His team provided this assessment of a whole host of entities that provide leukemia care.
* Dr. Jonathan Kenyon and colleagues found that normal individuals over age 50 begin to show evidence that genetic mutations are accumulating in marrow stem cells. This finding might be the key underlying the increased risk of anemias, myelodysplastic syndrome and acute leukemia in older individuals.
* Dr. Kevin Bunting¡¦s laboratory gave two important presentations on how intracellular STAT5 (an intracellular signaling protein) influences normal pathologic hematopoiesis (blood cell formation) and stem cell engraftment.
* Dr. Shigemi Matsuyama and colleagues presented a novel way of treating chemotherapy -induced thrombocytopenia (decrease in number of platelets in the blood) using Bax Inhibiting Peptides to rescue the damaged cells.
* Dr. Keith McCrae and colleagues presented that ƒ"2 glycoprotein is a cofactor in the process that dissolves blood clots through the use of the medical agent tPA.
University Hospitals of Cleveland
¡§This study is the first to show the success of treatment with evidence that stem cells now carry the new gene,¡® says Dr. Gerson, Director of the Ireland Cancer Center and Case Comprehensive Cancer Center, who spearheaded the Phase I study along with a team of researchers. ¡§These patients show the success of treatment with evidence that their stem cells now carry the new genes. This is a breakthrough ¡V the first time selection with MGMT has been shown to occur in patients.¡®
Preclinical animal research, conducted by Dr. Gerson and his colleagues, has shown that the gene G156A-MGMT can provide stem cells with very high levels of drug resistance, compared to normal stem cells not carrying the gene. In the Phase I trial for patients with advanced malignancies, researchers collected peripheral blood stem cells from patients and exposed them to a retrovirus containing the G156A-MGMT gene.
In addition to this promising research, Ireland Cancer Center scientists presented 24 oral and poster presentations at ASH. ¡§The breadth and depth of this innovative hematologic research at the Ireland Cancer Center are outstanding,¡® says Alvin Schmaier, MD, Chief of Hematology/Oncology at UHCMC and Case Western Reserve University School of Medicine. ¡§Our faculty is making tremendous advances in these fields which is reflected in their being chosen for oral and poster presentations.¡®
The presentations include:
* Dr. Hillard Lazarus and colleagues presented significant findings that treatment with Rituximab before transplantation results in cure rate and overall survival in patients undergoing autologous stem cell transplantation for Diffuse Large B-Cell lymphoma.
* Dr. Lazarus and colleagues of the Eastern Cooperative Oncology Group (ECOG) presented data that show that Imatninib (Gleevec) does not change outcomes on patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia.
* Dr. Lazarus presented an assessment of data over 30 years regarding acute leukemia and its management. He found that all avenues lead to stem cell transplantations. His team provided this assessment of a whole host of entities that provide leukemia care.
* Dr. Jonathan Kenyon and colleagues found that normal individuals over age 50 begin to show evidence that genetic mutations are accumulating in marrow stem cells. This finding might be the key underlying the increased risk of anemias, myelodysplastic syndrome and acute leukemia in older individuals.
* Dr. Kevin Bunting¡¦s laboratory gave two important presentations on how intracellular STAT5 (an intracellular signaling protein) influences normal pathologic hematopoiesis (blood cell formation) and stem cell engraftment.
* Dr. Shigemi Matsuyama and colleagues presented a novel way of treating chemotherapy -induced thrombocytopenia (decrease in number of platelets in the blood) using Bax Inhibiting Peptides to rescue the damaged cells.
* Dr. Keith McCrae and colleagues presented that ƒ"2 glycoprotein is a cofactor in the process that dissolves blood clots through the use of the medical agent tPA.
University Hospitals of Cleveland
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The generation of new nerve cells in the brain is regulated by a peptide known as C3a, which directly affects the stem cells' maturation into nerve cells and is also important for the migration of new nerve cells through the brain tissue, reveals new research from the Sahlgrenska Academy published in the journal Stem Cells.
Gene 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.
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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.
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