Syndicate content

Archive

April 21st, 2009

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]

April 17th

Possible Cell Adhesion Role for Normal Prion Protein

Scientist have reported the creation of a strong loss-of-function phenotype for the normal prion protein (PrP) in zebrafish embryos. This phenotype is characterized by the loss of embryonic cell adhesion and arrested gastrulation. The results of additional experiments indicate that the normal prion protein (1) mediates Ca+2-independent homophilic cell adhesion and signaling; and (2) modulates Ca+2-dependent cell adhesion by regulating the delivery of E-cadherin to the plasma membrane. The authors stated that their data uncover evolutionarily conserved roles of PrP in cell communication, which ultimately impinge on the stability of adherens cell junctions during embryonic development. The results were published in PLoS Biology, and an accompanying paper comments on the results.

Inbreeding Role in Extinction of the Spanish Habsburg Dynasty

Statistical genetic evidence supports the history-based theory that inbreeding may have played a role in the extinction of the Spanish Habsburg dynasty (1516-1700). This is the conclusion of research reported in an April 15 article in PLoS. The Spanish Habsburg dynasty was characterized by the frequent marrige of close relatives, in such a way that uncle-niece, first cousin, and other consanguineous unions were common. The dynasty ended with the childless death of the physically and mentally disabled Charles II at the age of 39. [PLoS article]

Molecular Switch Inhibition May Aid Treatment of Deadly Brain Cancers

Inhibition of the expression of a gene called NHERF-1 may be useful in the treatment of deadly brain cancers in the class glioblastoma multiforme (GBM), according to findings published by researchers at the Translational Genomics Research Institute (TGen) and Barrow Neurological Institute in the April issue of Neoplasia. "Our findings suggest a novel mechanism defining NHERF-1 as a 'molecular switch' that regulates the GBM tumor cell's ability to migrate or divide,'' said Dr. Kerri Kislin, the lead author of the study. The findings will be presented during the AACR annual meeting April 18-22. [Press release]