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October 19, 2007, 5:07 AM CT

Sidestepping cancer's chaperone

Sidestepping cancer's chaperone
Malignant tumors are wildly unfavorable environments. Struggling for oxygen and nutrients while being bombarded by the bodys defense systems, tumor cells in fact require sophisticated adaptations to survive and grow. For decades, researchers have sought ways to circumvent these adaptations to destroy cancer. Now, scientists at the University of Massachusetts Medical School (UMMS), have defined a method to target and kill cancers chaperonea protein that promotes tumor cell stability and survivalwithout damaging healthy cells nearby.

In Regulation of Tumor Cell Mitochondrial Homeostasis by an Organelle-Specific Hsp90 Chaperone Network, reported in the October 19 issue of Cell, Dario C. Altieri, MD, the Eleanor Eustis Farrington Chair in Cancer Research and professor and chair of cancer biology, and his colleagues at UMMS, identify a new pathway by which cancer cells grow and surviveand provide a clear blueprint for the design and production of a novel class of anticancer agents aimed squarely at that pathway.

While prior research has demonstrated that a class of proteins known as molecular chaperones promote tumor cell survival, the specific way in which the proteins achieve this has not been well understood. And eventhough inhibitors of a specific chaperone known as heat shock protein 90 (Hsp90) have been studied for the therapy of cancer, progress has been questionable. In this current research, Dr. Altieri and his colleagues sought to both define the mechanism by which Hsp90 leads to tumor cell stability and survival, and understand why general suppression of Hsp90 has not been as successful in clinical trials.........

Posted by: Janet      Read more         Source


October 19, 2007, 5:05 AM CT

The specific cell that causes eye cancer

The specific cell that causes eye cancer
Retinoblastoma
Investigators at St. Jude Children's Research Hospital have identified the cell that gives rise to the eye cancer retinoblastoma, disproving a long-standing principle of nerve growth and development. The finding suggests for the first time that it may one day be possible for researchers to induce fully developed neurons to multiply and coax the injured brain to repair itself.

A report of this work appears in the Oct. 19 issue of the journal Cell. Michael Dyer, Ph.D., an associate member in the St. Jude Department of Developmental Neurobiology, is the reports senior author.

Retinoblastoma arises in the retinathe multi-layered, membrane lining the back of the eye that responds to light by generating nerve impulses that are carried into the brain by the optic nerve.

The immediate importance of the St. Jude finding is that it unexpectedly showed that retinoblastoma can arise from fully matured nerves in the retina called horizontal interneurons. This disproves the scientific principle that fully formed, mature nerves cannot multiply like young, immature cells, Dyer said. Human neurodegenerative disorders such as Alzheimers disease can occur when differentiated nerves in the brain try to multiply, and in the process, trigger a self-destruct program called apoptosis. Differentiation is the process by which cells lose their primitive, stem-cell-like properties that include the ability to grow and multiply, and instead develop specialized shapes and functions.........

Posted by: Mike      Read more         Source


October 17, 2007, 9:32 PM CT

Feeling sleepy is all in your genes

Feeling sleepy is all in your genes
Genes responsible for our 24 hour body clock influence not only the timing of sleep, but also appear to be central to the actual restorative process of sleep, as per research reported in the online open access journal BMC Neuroscience. The study identified changes in the brain that lead to the increased desire and need for sleep during time spent awake.

"We still do not know why we benefit from sleep, or why we feel tired when we are 'lacking' sleep, but it seems likely that sleep serves some basic biological function for the brain such as energy restoration for brain cells or memory consolidation." Explains Dr Bruce O'Hara of the University of Kentucky, one of the neuroresearchers who conducted the research. "We have observed that clock gene expression in the brain is highly corcorrelation to the build-up of sleep debt, while prior findings have linked these genes to energy metabolism. Together, this supports the idea that one function of sleep is correlation to energy metabolism".

To explore the correlation between the expression of clock genes and sleep, three inbred strains of mice with different genetic make-ups were utilized, and which had previously been shown to differ in their response to sleep deprivation by lead author, Dr. Paul Franken of Stanford University and Lausanne University. In this study, mice were first sleep deprived during the daytime period when mice normally sleep then allowed recovery sleep. Changes in gene expression for three clock genes were examined throughout the brain during both phases. Clock gene expression generally increased the more the mice were kept awake and decreased when sleep was allowed, supporting that these genes play a role in the regulation of the need for sleep. Generally, the expression of the clock-genes Period-1 and Period-2, increased at a faster rate in mouse strains with the poorest quality of recovery sleep suggesting that the detailed dynamic changes in expression may underlie individual differences in sleep length and sleep quality. The changes in gene expression were also shown to occur in a number of different brain regions supporting the idea that sleep is a global brain function.........

Posted by: JoAnn      Read more         Source


October 17, 2007, 8:21 PM CT

HPV test beats Pap in detecting cervical cancer

HPV test beats Pap in detecting cervical cancer
A new study led by McGill University scientists shows that the human papillomavirus (HPV) screening test is far more accurate than the traditional Pap test in detecting cervical cancer. The first round of the Canadian Cervical Cancer Screening Trial (CCCaST), led by Dr. Eduardo Franco, Director of the Division of Cancer Epidemiology at McGill's Faculty of Medicine, concluded that the HPV test's ability to accurately detect pre-malignant lesions without generating false negatives was 94.6%, as opposed to 55.4% for the Pap test.

The results of the study, first-authored by Dr. Francos former McGill PhD student Dr. Marie-Hlne Mayrand of the Centre hospitalier de l'Universit de Montral (CHUM), with colleagues from McGill, Universit de Montral, the Newfoundland and Labrador Public Health Laboratory and McMaster University, are reported in the October 18 issue of The New England Journal (NEJM).

CCCaST is the first randomized controlled trial in North America of HPV testing as a stand-alone screening test for cervical cancer. The first round followed 10,154 women aged 30 to 69 in Montreal, Quebec and St. John's, Newfoundland who were enrolled in the study from 2002 to 2005. The study was funded by a grant from the Canadian Institutes of Health Research (CIHR).

The study concluded that while the HPV test's sensitivity was nearly 40% greater than the Pap tests, the Pap did, however, slightly edge out HPV for accuracy on the specificity scale -- its ability to accurately detect pre-malignant lesions without generating false positives -- at 96.8% versus 94.1%.........

Posted by: Emily      Read more         Source


October 17, 2007, 4:47 AM CT

Gold nanorods to fighting cancer

Gold nanorods to fighting cancer
Scientists have shown how tiny "nanorods" of gold can be triggered by a laser beam to blast holes in the membranes of tumor cells, setting in motion a complex biochemical mechanism that leads to a tumor cell's self-destruction.

Tumor cell membranes often have an abnormally high number of receptor sites to capture molecules of folic acid, or folate, a form of vitamin B that a number of tumor cells crave. The Purdue scientists attached folate to the gold nanorods, enabling them to target the receptors and attach to the tumor cell membranes.

"The cells are then illuminated with light in the near-infrared range," said Ji-Xin Cheng (pronounced Gee-Shin), an assistant professor in Purdue's Weldon School of Biomedical Engineering. "This light can easily pass through tissue but is absorbed by the nanorods and converted rapidly into heat, leading to miniature explosions on the cell surface".

Researchers have recently determined that gold nanorods and other nanostructures can be used to target and destroy tumor cells, but it was generally assumed that cell death was due to the high heat produced by the light-absorbing nanoparticles. The Purdue team discovered, however, that a more complex biochemical scenario is responsible for killing the cells.

"We have observed that rather than cooking the cells to death, the nanorods first punch holes in the membrane, and cell death is then chemically induced, in this case by an influx of calcium," said Alexander Wei, an associate professor of chemistry at Purdue.........

Posted by: Janet      Read more         Source


October 16, 2007, 7:38 PM CT

How schizophrenia develops

How schizophrenia develops
Schizophrenia may occur, in part, because of a problem in an intermittent on/off switch for a gene involved in making a key chemical messenger in the brain, researchers have found in a study of human brain tissue. The scientists observed that the gene is turned on at increasingly high rates during normal development of the prefrontal cortex, the part of the brain involved in higher functions like thinking and decision-making but that this normal increase may not occur in people with schizophrenia.

The study was funded by the National Institutes of Healths National Institute of Mental Health (NIMH) and National Institute of Child Health and Human Development.

The gene, GAD1, makes an enzyme essential for production of the chemical messenger, called GABA. The more the gene is turned on, the more GABA synthesis can occur, under normal circumstances. GABA helps regulate the flow of electrical traffic that enables brain cells to communicate with each other. It is among the major neurotransmitters in the brain.

Abnormalities in brain development and in GABA synthesis are known to play a role in schizophrenia, but the underlying molecular mechanisms are unknown. In this study, researchers discovered that defects in specific epigenetic actions biochemical reactions that regulate gene activity, such as turning genes on and off so that they can make substances like the GAD1 enzyme are involved.........

Posted by: JoAnn      Read more         Source


October 12, 2007, 5:09 AM CT

Molecules that block cancer cells from modifying cell DNA

Molecules that block cancer cells from modifying cell DNA
Scientists have discovered new small molecules that may prevent prostate cancer cells from turning off normal genes in a process that transforms normal cells into cancer cells. This significant discovery in the field of epigenetics has immediate implications in the development of new diagnostic tests and cancer medications. The findings were presented today at the Prostate Cancer Foundations annual Scientific Retreat. Funding for the research was provided by the Prostate Cancer Foundation, as well as from the National Cancer Institute and the Avon Foundation.

Epigenetics refers to changes to genes other than changes to the DNA sequence itself, such as the addition of molecules to the DNA strand. While the development of cancer can arise from defective or mutated genes, it can also arise from these changes that can actually prevent a cell from acting as it should. Cancer cells exploit this process, putting some genes in cold storage or turned off by modifying the cell DNA in a process known as methylation.

Lead researcher William Nelson, M.D., Ph.D., Professor of Oncology and Urology at the Johns Hopkins Kimmel Cancer Center, explained the findings. One of the proteins in the cell that triggers this process is called a methyl-CpG binding protein, or MBD. We have discovered an antagonist of MBD2 that keeps this protein from binding to methylated genes. If the protein cant bind to the gene, then it cant keep the gene turned off and the gene is turned back on able to act in the way it is supposed to.........

Posted by: Janet      Read more         Source


October 12, 2007, 5:00 AM CT

Anticlotting drug safe in sickle cell patients

Anticlotting drug safe in sickle cell patients
An intravenous blood thinner widely used in patients with acute coronary syndromes and during coronary artery stent placement appears to be safe in patients with sickle cell disease and may have beneficial anti-inflammatory effects, a small study at the University of North Carolina at Chapel Hill School of Medicine has found.

We have tested a potentially promising drug in sickle cell patients, and the drug appears to be well tolerated. This gives us the impetus to go ahead with further studies of eptifibatide in these patients, said Dr. Leslie V. Parise, department chair and professor of biochemistry and biophysics at the UNC-Chapel Hill School of Medicine.

The hallmark of sickle cell disease is malformed red blood cells that can cause sudden painful episodes when they block small blood vessels. However, sickle cell patients are also at increased risk of developing multiple other complications, including strokes, lung complications and pulmonary hypertension.

The most frequent manifestations of sickle cell disorders are anemia and pain episodes. The episodic exacerbation of pain, often called crises, is unpredictable and may occur often in some patients.

The only drug presently approved for the therapy of sickle cell disease is hydroxyurea, which has been shown to reduce the frequency of painful episodes.........

Posted by: Scott      Read more         Source


October 10, 2007, 5:23 PM CT

Brain circuits used in sensation of touch

Brain circuits used in sensation of touch
The ability to tactually recognize fine spatial details, such as the raised dots used in braille, is particularly important to those who are blind. With that in mind, a team of scientists has identified the neural circuitry that facilitates spatial discrimination through touch. Understanding this circuitry may lead to the creation of sensory-substitution devices, such as tactile maps for the visually impaired.

The findings are reported in the Oct. 10 edition of The Journal of Neuroscience.

The research team, led by Krish Sathian, MD, PhD, professor of neurology in Emory University School of Medicine, included first author Randall Stilla, research MRI technologist at Emory, and Gopikrishna Deshpande, Stephen Laconte and Xiaoping Hu of the Coulter Department of Biomedical Engineering at Georgia Tech and Emory.

Using functional magnetic resonance imaging (fMRI), the scientists found heightened neural activity in a network of frontoparietal regions of the brain when people engaged in fine tactile spatial discrimination. Within this network, the levels of activity in two subregions of the right posteromedial parietal cortex--the right posterior intraparietal sulcus (pIPS) and the right precuneus--were predictive of individual participants' tactile sensitivities.........

Posted by: Daniel      Read more         Source


October 10, 2007, 5:09 AM CT

Revimmune for refractory MS

Revimmune for refractory MS
Accentia Biopharmaceuticals announces that it met with the Food and Drug Administration (FDA) on September 26, 2007 for a scheduled pre-Investigational New Drug (pre-IND) meeting on Revimmune. The FDA has indicated its support for Accentia to submit an IND for a pivotal Phase 3 randomized controlled, multi-center clinical trial of Revimmune, the companys potential therapeutic for refractory, relapsing-remitting Multiple Sclerosis (MS). The FDA indicated that they support the proposed submission from Accentia and that they are in overall agreement with the proposed design of the Accentia clinical program.

The Revimmune MS study will enroll subjects in a one-year study comparing baseline disability to disability at month 12 with an interim data analysis. After consultation with the FDA on the design of the trial, it was agreed that the primary endpoint will be recovery of lost function and that this unique study will be done under a special protocol assessment (SPA). Accentia will proceed diligently with submission of the IND under a SPA and of an application for Fast Track status, and currently projects commencement of the Phase 3 study in the first half of 2008. A Special Protocol Assessment is a declaration from the Food and Drug Administration that a proposed Phase 3 trial 's design, clinical endpoints, and statistical analyses are acceptable for FDA approval. All previous approved therapeutics suppress rather than eliminate autoimmunity and they have used the more limited indication of a reduction in the rate of progression of disability as their primary endpoint, not a reduction in disability as for Revimmune.........

Posted by: Daniel      Read more         Source



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Did you know?
Scientists at Yale have brought to light a mechanism that regulates the way an internal organelle, the Golgi apparatus, duplicates as cells prepare to divide, according to a report in Science Express.Graham Warren, professor of cell biology, and colleagues at Yale study Trypanosoma brucei, the parasite that causes Sleeping Sickness. Like a number of parasites, it is exceptionally streamlined and has only one of each internal organelle, making it ideal for studying processes of more complex organisms that have a number of copies in each cell.

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