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BREAST CANCER: GENE ESSENTIAL TO METASTASIS IS IDENTIFIED
SATB1, a nuclear protein known as a key player in the immune system because of its crucial role in regulating gene expression during the differentiation and activation of T cells, has been shown to be an essential contributing factor in the most aggressive forms of breast cancer, researchers at Lawrence Berkeley National Laboratory in Berkeley, California report. The findings, published in Nature, represent a new paradigm for understanding the way tumors progress. Breast cancer cells need SATB1 to break away from the original tumor and spread to other parts of the body. This process, known as metastasis, is the final step of solid tumor progression and is the most common cause of death in cancer patients. The researchers found that introducing SATB1 into otherwise nonmetastatic breast cancer cells, invasive tumors can be induced in mice. Conversely, removing SATB1 from metastatic cells not only abolishes metastasis and tumor growth in mice but also returns cells to their normal appearance in vitro. The analysis showed that a high level of SATB1 expression by itself is an excellent indicator of poor prognosis--independent of whether breast cancer cells have already metastasized to the lymph nodes at the time of diagnosis.

 

AUSTISM: MICE COULD PROVIDE CLUES TO DISORDER BEHAVIORS
Scientists have developed a new mouse model to help illuminate the vagaries of autism, according to a study from a Stanford University School of Medicine researcher and other colleagues. The study, published in the journal Behavioral Brain Research, focused on mice missing the gabrb3 gene, which codes for a protein important in brain development and normal adult brain function. Autism occurs approximately once in every 150 births, with males being four times more likely to develop this disorder. The team found that their mouse model displays two of autism’s three main traits: social deficiency and repetitive actions. The mice also exhibit other autism-associated characteristics, such as abnormal exploratory behavior, and deficits in nonselective attention, thought to be involved in shifting or orienting attention from one target or place to another.

PATENTS: USPTO UPHOLDS REMAINING WARF STEM CELL PATENTS

The United States Patent and Trademark Office has upheld the claims of the Wisconsin Alumni Research Foundation or WARF by making determinations on the non-profit foundation’s two most important base embryonic stem cell patents. The decisions are final and cannot be appealed. They follow the affirmation in February of a third patent held by WARF, a private supporting organization of the University of Wisconsin. The decision affects two patents for primate and human embryonic stem cells known as “780” and “806.” The decision to uphold the patents concludes a review process for “780” and “806” that began in October 2006, when the patent office agreed to reexamine the patents following challenges brought by the New York-based Public Patent Foundation and the California-based Foundation for Taxpayer and Consumer Rights. The foundation charged the patents were overreaching, were wrongly granted and have impeded research.

ALZHEIMER’S: PARADOXICAL FINDING OFFERS NEW INSIGHT INTO MEMORY LOSS
Researchers at the Novato, California-based Buck Institute believe a normal process of culling inconsequential information from the brain in a constant process of house cleaning is hyper-activated in Alzheimer’s disease and that this effect is key to the profound memory loss associated with the incurable neurodegenerative disorder. Last year, this same group of researchers found that they could completely prevent Alzheimer’s disease in mice genetically engineered with a human Alzheimer’s gene by blocking a single site of cleavage of one molecule, called APP for amyloid precursor protein. Normally, this site on APP is attacked by molecular scissors called caspases, but blocking that process prevented the disease. Now they have studied human brain tissue and found that, just as expected, patients suffering from AD clearly show more of this cleavage process than people of the same age who do not have the disease. However, when they extended their studies to much younger people without Alzheimer’s disease, they found an apparent paradox: these younger people displayed as much as 10 times the amount of the same cleavage event as the AD patients. The researchers now believe they know why. The Buck Institute study implicates a biochemical “switch” associated with that cleavage of APP, causing AD brains to become stuck in the process of breaking memories, and points to AD as a syndrome affecting the plasticity or malleability of the brain. The study, published in the Journal of Alzheimer’s Disease, provides new insight into a molecular event resulting in decreased brain plasticity, a central feature of AD.

 

OVARIAN CANCER: VERMILLION’S BIOMARKERS IDENTIFY WOMEN WITH EARLY-STAGE DISEASE
Fremont, California-based Vermillion presented data from several studies demonstrating the benefits of the company's ovarian cancer protein biomarker panel. The company said the data suggest that use of its biomarkers could help better identify women with ovarian cancer, as well as improve the detection of early-stage disease. Results of these studies were presented at the Society of Gynecologic Oncologists' 39th Annual Meeting on Women's Cancer in Tampa, Florida. Results demonstrated that the biomarker panel could more than double the number of ovarian cancer cases referred to a gynecologic oncologist, thereby improving survival rates and reducing the number of surgeries performed. The ovarian cancer detection study showed that Vermillion's panel of biomarkers in combination with CA-125 could more accurately identify early-stage ovarian cancer than could CA-125 alone. CA-125 is the only tumor marker for ovarian cancer currently available on the market; however, it is not cleared for early-stage disease detection. When examining stage-1 disease, the combination of the two markers correctly identified 87 percent of the cancers. Vermillion worked in collaboration with researchers from the University of Texas M.D. Anderson Cancer Center on this research.

 

Molecular biologists at the University of California, San Diego have found one piece of the complex puzzle of autophagy, the process of “self-eating” performed by eukaryotic cells (cells with a nucleus) to keep themselves healthy. All eukaryotic cells dispose of bacteria, viruses, damaged organelles, and other non-essential components through this self-eating process. The findings, published in the journal Developmental Cell, are important because it allows scientists to control this one aspect of cellular autophagy, and may lead to the ability to control other selective “self-eating” processes. This, in turn, could help illuminate autophagy’s role in aging, immunity, neurodegeneration, and cancer, the researchers said. The researchers identified a novel protein called Atg30 (one of 31 required for autophagy-related processes) from the yeast Pichia pastoris, that controls the degradation of a sub-compartment of cells, the peroxisomes.

Peroxisomes generate and dispose of harmful peroxides that are by-products of oxidative chemical reactions.

 

South San Francisco, California-based Monogram Biosciences said it signed an agreement with Avexa to be the exclusive provider of HIV diagnostic technology to support Avexa’s drug discovery and development programs. Avexa plans to use Monogram's assays across its virology portfolio, including the late-stage clinical program for its lead compound, apricitabine. Apricitabine is an HIV drug in the nucleoside reverse transcriptase inhibitor (NRTI) class. Melbourne, Australia-based Avexa plans to use Monogram's PhenoSense GT assay to select patients and optimize background therapy for trials involving approximately 2,000 patients, and to monitor response to drug treatment during the trials. ATC is a new nucleoside analog that is intended for use in patients who have developed viral resistance to existing drugs. Avexa also has HIV drugs in early development in the CCR5- and integrase- inhibitor classes. As recommended by the U.S. FDA Antiviral Drugs Advisory Committee, biopharmaceutical companies are using HIV-resistance testing technology to support and enhance next-generation HIV drug development. Monogram's proprietary technology is being applied to new HIV drug targets for screening and in subsequent clinical development programs for optimization of background therapy, patient monitoring and, in the case of CCR5 antagonists, for patient selection.

BLOOD REPLACEMENT: SAFETY MONITORING BOARD RECOMMENDS SANGART TRIALS CONTINUE
San Diego-based Sangart said that an independent data safety monitoring board has recommended the continuation of both of its late-stage clinical trials of its lead blood substitute product, Hemospan. The recommendation is based on the board’s review of the blinded data from the first two-thirds of the 830 patients to be enrolled in two ongoing pivotal late-stage clinical trials in Europe. The board conducted a prior review in December 2007 that concluded positively. Hemospan is a hemoglobin-based oxygen transport agent designed to serve as an oxygen therapeutic and as an alternative to blood transfusions. A key property of Hemospan is its high oxygen affinity, which results in targeted oxygen delivery to tissues at risk of oxygen deprivation, the company said.

 

South San Francisco, California-based Raven Biotechnologies said it has initiated a mid-stage clinical trial of its lead clinical product, a chimeric monoclonal antibody known as RAV12, in combination with gemcitabine in the treatment of patients with metastatic pancreatic cancer. RAV12 is directed against a sugar structure that is widely displayed on the surfaces of tumor cells, particularly those of gastroesophageal, pancreatic, and colorectal cancers. Adenocarcinoma of the pancreas is a major unmet medical need and represents the fourth leading cause of cancer death in the United States. Approximately 34,000 new cases of pancreatic cancer are reported in the US each year.

 

Pasadena, California-based Calando Pharmaceuticals, a leading siRNA therapeutics company, announced today that the company has submitted an investigational new drug application to the U.S. Food and Drug Administration to initiate an early-stage clinical trial using their lead anti-cancer compound, CALAA-01. The drug candidate is a targeted nanoparticle, comprised of a proprietary, non-chemically-modified siRNA against a clinically-validated cancer target. RNA interference, or RNAi, is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new class of medicines to treat a wide range of human diseases.

 

DNA IMMUNOTHERAPIES: INOVIO’S DELIVERY TECHNOLOGY DEMONSTRATES SAFETY AND CLINICAL REPSONSE
San Diego-based Inovio Biomedical said that interim data from a first-in-man clinical trial demonstrated that a DNA-based immunotherapy against metastatic melanoma, delivered using Inovio’s electroporation delivery technology, was safe and also produced durable local and systemic tumor regression. Electroporation uses short electrical pulses to allow DNA to enter the cell. Inovio’s electroporation delivery technology is intended to enhance the potency of DNA-based immunotherapies, including DNA vaccines, against cancers and infectious diseases. The company said its electroporation-based DNA immunotherapy was safe and tolerable. Furthermore, despite starting from nominal dose levels and without reaching dose-limiting toxicity, this therapy achieved evidence of durable local and systemic tumor regression. This study suggests that electroporation-mediated plasmid delivery is a powerful new tool for effective gene transfer, with implications for the clinical arena, and further clinical evaluation of this therapy is warranted.” Researchers presented the data at the DNA Vaccines Forum 2008 in London.