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April 23rd, 2009

New Drug Starves Brain Cancer Cells

In animal studies, researchers have shown that a new drug (3-BrOP) is effective at starving neuroblastoma cells and reducing tumor growth by 75%. The drug, developed by scientists at the University of Texas M.D. Anderson Center, is an inhibitor of glycolysis, the energy-producing process upon which neuroblastoma cells are highly dependent. Neuroblastoma is a childhood brain cancer, and estimates are that approximately 650 children under the age of 5 are diagnosed with this cancer each year in the United States. Long-term survival of patients with metastatic neuroblastoma is less than 40% because the tumors are often resistant to traditional chemotherapy. The new research results were reported at the 22nd annual meeting of the American Society of Pediatric Hematology/Oncology. [Press release]

April 22nd

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April 21st

Gene Signature Associated with Gleevec Resistance in GIST Patients

A genetic signature associated with increased resistance to Gleevec in patients with gastrointestinal stromal tumors (GIST) has been identified by researchers at the Fox Chase Cancer Center. Efforts to affect the expression and/or activity of genes in the signature may help increase the responsiveness to Gleevec in resistant patients. Currently, approximately 80% of GIST patients are responsive to Gleevec. This work was presented at the annual AACR meeting April 18-22. [Press release]

Clues to Mechanism of Lithium Action in Bipolar Disease

New research provides insights into how lithium works in the treatment of bipolar mood disorder, and may lay the groundwork for advances in the treatment of this disease. Scientists from Cardiff University, together with colleagues, have shown that lithium inhibits the enzyme inositol monophosphatase, and this leads to the inhibition of the production of PIP3, a molecule that is important in controlling brain cell signaling. Professor Adrian Harwood of Cardiff School of Biosciences, who led the research, said "We still cannot say definitively how lithium can help stabilize bipolar disorder. However, our research does suggest a possible pathway for its operation. By better understanding lithium, we can learn about the genetics of bipolar disorder and develop more potent and selective drugs. Further, altered PIP3 signalling is linked to other disorders, including epilepsy and autism, so this well established drug could be used to treat other conditions." The research was published in Disease Models & Mechanisms. [Press release]

April 20th

DICER1 Mutations Implicated in Rare Childhood Cancer

Mutations in the microRNA processing enzyme DICER1 appear to the cause of the inherited form of a rare, aggressive childhood cancer called pleuropulmonary blastoma (PPB). "PPB is the first malignancy found to be directly associated with inherited DICER1 mutations, making the cancer an important model for understanding how mutations and loss of DICER1 function lead to cancer," says lead author D. Ashley Hill, M.D., chief of pathology at Children's National Medical Center. "Additionally, we now believe that PPB tumors arise from an unusual mechanism in which cells carrying mutations induce nearby cells to become cancerous without becoming cancerous themselves." The results of this study were presented April 19 at the annual AACR meeting. [Press release]

Possible New Avenue for Huntington Disease Treatment

Increasing the levels of a key protein (RCAN1-1L) can, in vitro, rescue cells from the toxic effects of mutant huntingtin proteins that cause Huntington disease. "Our findings allow for the possibility that controlled over-expression of RCAN1-1L might in the future be a viable avenue for therapeutic intervention in Huntington disease patients," said Kelvin J. A. Davies, professor of gerontology in the USC Davis School of Gerontology and professor of biological sciences in the USC College of Letters, Arts and Sciences, and an author of the study. The report is now available online and will be published in June 2009 in the Journal of Biological Chemistry. [Press release] [JBC article]

April 19th

Novel Drug Targeted at Cancer Stem Cells Shows Promise in Pancreatic Cancer

The combination of a novel drug (tigatuzumab) directed against pancreatic cancer stem cells, and the drug (gemcitabine) currently used for the treatment of pancreatic cancer, has shown promising results in achieving tumor remission and preventing recurrence. Tigatuzumab is a humanized antibody directed against death receptor-5, which the researchers showed is overexpressed in pancreatic cancer stem cells. In the studies, ten patient-derived tumors were implanted in laboratory mice and the effects of the combination therapy were evaluated. Treatment with gemcitabine and tigatuzumab resulted in the reduction of pancreatic cancer stem cells, caused tumor remission, and significantly increased time-to-tumor progression in fifty percent of treated cases from a median of 54 days to 103 days. These results were obtained by researchers from Johns Hopkins and colleagues, and will be presented at the annual AACR meeting April 18-22. [Press release]

Nine New X-Chromosome Genes Associated with Learning Disabilities

Researchers have identified nine new genes on the X-chromosome that, when mutated, are associated with learning disabilities. "We sequenced 720 out of the approximately 800 known genes on the X chromosome in more than 200 families affected by X-linked learning disabilities," explained Professor Michael Stratton, from the Wellcome Trust Sanger Institute. "This is the largest sequencing study of complex disease ever reported." Learning disability is significantly more common in males than in females, and genetic causes have long been sought on the X-chromosome as males have only one X chromosome and so a gene mutation on the X is more likely to have an effect in males than in females. These new findings are expected to aid the diagnoses of X-linked learning disabilities and to enable more comprehensive genetic counseling. [Press release] [Nature Genetics abstract]

April 18th

Synthesis of Anti-Leukemia Compounds from South Pacific Sponge

Scientists at the Scripps Research Institute have succeeded in synthesizing kapakahines, compounds with anti-leukemia potential that are normally produced in vanishingly small quantities by the South Pacific tube-type sponge Cripbrochalina olemda. With the synthetic process in hand, it will be possible, for the first time, to produce kapakahines in quantities sufficient for thorough study of their effectiveness in combating leukemia. [Press release] [JACS abstract]

Origins of Deadly Prostate Cancer Traced to Single Aberrant Cell

The origins of metastatic prostate cancer cells can be traced to a single original cancer cell in individuals. This is the conclusion of a 14-year autopsy-based study of copy number variation in the cells of prostate cancer victims. The study was carried out by researchers at Johns Hopkins and collaborating institutions. The findings call into question current views of the origins of primary prostate cancer and suggest that the genomic profile of prostate cancer metastases should inform therapeutic decisions. [Press release] [Nature Medicine abstract]