<?xml version="1.0" encoding="us-ascii"?><rss version="2.0"><channel><title>NIH OTT RSS Feed - All Classifications</title><link>http://www.ott.nih.gov/rss/default.aspx</link><description>Office of Technology Transfer (OTT).</description><copyright>Copyright 2009 NIH Office of Technology Transfer (OTT). All rights reserved.</copyright><item><title>Vortex Counter-Current Chromatography (CCC) System</title><description><![CDATA[Available for licensing and commercial development is a vortex counter-current chromatography system. The system has a rotary frame engaged to a vortex separation column for rotation in one direction through a vortex separation shaft engaged to a pulley system. The rotary frame is engaged to a central shaft that rotates the rotary frame in a direction opposite that of the vortex separation column such that planetary motion is imparted to the vortex separation column. The vortex separation column may be configured to receive a solvent system separable between two immiscible liquid phases introduced into the vortex separation column. A pulley system is operatively engaged to the separation column shaft and the central shaft for rotating the separation column shaft and the cortex separation column in a synchronous rotational direction opposite to the rotational direction of the rotary frame for imparting a type-I planetary motion to the vortex separation column. A counter-weight column is engaged at a symmetrical position opposite the vortex separation column along the rotary frame, wherein the two immiscible liquid phases undergo a vortex motion during rotation of the vortex separation column such that mixing of the two immiscible liquid phases takes place with a plane perpendicular to an axis of the vortex separation column.

Compared with conventional CCC systems, the vortex system has much higher partition efficiency in terms of height equivalent to a theoretical plate (only 2 cm compared with 20 cm that is required for the conventional system).  The vortex system also provides an advantage of low column pressure which facilitates application of a large industrial-scale separation without a risk of leakage of solvent and column damage caused by high pressure.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2156</link><pubDate>2010-09-01</pubDate></item><item><title>A Nurr1-Knockout Mouse Model for Parkinson's Disease and Stem Cell Differentiation</title><description><![CDATA[The researchers have generated Nurr1-knockout mice via genomic locus inactivation using homologous recombination.

Transcription factor Nurr1 is an obligatory factor for neurotransmitter dopamine biosynthesis in ventral midbrain. From a neurological and clinical perspective, it suggests an entirely new mechanism for dopamine depletion in a region where dopamine is known to be involved in Parkinson's disease.  Activation of Nurr1 may be therapeutically useful for Parkinson's disease patients; therefore, the mice would be useful in Parkinson's disease research.

Additionally, Nurr1 has been shown to be critical for development of midbrain dopaminergic neurons, and thus may contribute to stem cell-based therapies for neurological disorders.  Nurr1 is also important for osteoblast differentiation, suggesting a general role in stem cell differentiation and growth.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1288</link><pubDate>2010-08-31</pubDate></item><item><title>An XMRV Tool Box: Expression Plasmids, Genes, and Proteins for All Components of the Xenotropic Murine Leukemia Virus-Related Virus (XMRV)</title><description><![CDATA[The xenotropic murine leukemia virus-related virus (XMRV) has been implicated as a possible causative agent of prostate cancer and chronic fatigue syndrome (CFS). Starting in September 2009, scientists at the National Institutes of Health (NIH) and one of its life science contractors, SAIC-Frederick, have developed sixty four (64) protein expression plasmids for components of XMRV. One or more XMRV proteins made available through these expression plasmids could have clinical relevance to diagnosing or treating human disease. The work to develop this technology was performed in the Protein Expression Laboratory at SAIC-Frederick in collaboration with expert retrovirologists from the National Cancer Institute's Frederick, MD campus, a site well-positioned to develop these expression plasmids from initial cloning to final validations. The development of these XMRV tools is expected to save researchers months in laboratory production time and thousands of dollars in labor costs.

The XMRV strain utilized to generate these expression plasmids is a reference strain isolated from a human patient. Each expression plasmid encodes one of the ten proteins that comprise the XMRV retrovirus (matrix, p12, capsid, nucleocapsid, protease, reverse transcriptase, integrase, surface, transmembrane, and envelope). Nine of the ten XMRV proteins expressed by these clones have been successfully purified in large quantities using scale-up processes. The expression vectors were generated utilizing the Gateway? cloning system and consist of Gateway? entry clones, bacterial (Escherichia coli) expression clones, baculovirus expression clones, and mammalian expression clones. Expression of the appropriate XMRV protein from its corresponding expression clone has been confirmed. The entry clones have been validated for Gateway? subcloning and the baculovirus clones have been validated for baculovirus production and can be transposed into baculoviral genomes. The plasmids have been fully mapped and sequenced and contain one or more elements to facilitate laboratory use, such as antibiotic resistance genes, specialized promoter sequences, maltose-binding protein and His tags, TEV protease sites, Kozak-ATG sequences, signal peptides, and other elements.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2153</link><pubDate>2010-08-31</pubDate></item><item><title>Superresolution Microscopy via Azicon Beam Polarization Devices</title><description><![CDATA[The technology offered for licensing pertains to novel polarizers that produce tangentially and radially polarized beams. The polarizers and polarizing beam splitter of the technology include one or more pairs of axicons (also known as conical lenses) that are configured to separate an input beam into a radially polarized component and a tangentially (or azimuthally) polarized component. A second axicon pair can be positioned to recombine the tangentially polarized component so as to provide a more uniform beam intensity. The radial polarized component can be reflected or otherwise directed so that one or both the radial and tangential components are available for use.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2157</link><pubDate>2010-08-31</pubDate></item><item><title>Mucosal Cytotoxic T Lymphocyte Responses</title><description><![CDATA[The invention offered for licensing provides methods and compositions for induction of an antigen-specific, mucosal cytotoxic T lymphocyte (CTL) response useful in preventing and treating infections with pathogens that gain entry via a mucosal surface. The methods of the invention involve administering either a soluble antigen itself, or a polynucleotide encoding the soluble antigen, to a mucosal surface. The soluble antigens can be full length, naturally occurring polypeptides or fragments (i.e. peptides) derived from them. The soluble antigen is administered with an adjuvant at the mucosal site or without an adjuvant. Adjuvants can be, for example, Cholera toxin (CT), mutant CT (MCT), E. coli heat labile enterotoxin (LT) and others. Cytokines like IL-12 or IFNgamma can also be administered to enhance the immunoreactivity. Mucosal routes of administration include intrarectal (IR), intranasal (IN), intragastric (IG), intravaginal (IVG) or intratratracheal (IT). Soluble antigens can be derived from pathogenic viruses (e.g. HIV, influenza, or hepatitis virus), bacteria (e.g. Listeria monocytogenes), or prozoans. Furthermore, the soluble antigen can be tumor-associated antigen for cancer applications.

The utility of the technology has been extensively demonstrated when applied to HIV. Details about the HIV studies are provided in the eight (8) publications cited below.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=424</link><pubDate>2010-08-31</pubDate></item><item><title>Chimeric Anti-human ROR1 Monoclonal Antibodies</title><description><![CDATA[Available for licensing are mouse anti-human receptor tyrosine kinase-like orphan receptor 1 (ROR1) monoclonal antibodies (mAbs).  ROR1 is a signature cell surface antigen for B-cell chronic lymphocytic leukemia (B-CLL) and mantle cell lymphoma (MCL) cells, two incurable B-cell malignancies that are newly diagnosed in approximately 15,000 and 3,500 patients per year, respectively, in the United States.  Currently, there are no therapeutic mAbs that specifically target B-CLL or MCL cells.  Anti-ROR1 mAbs  may be linked to chemical drugs or biological toxins thus providing cytotoxic delivery to malignant B-cells and not normal cells.  Additionally, these antibodies can be fused to radioisotopes and can be used to diagnose B-CLL and MCL malignancies.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2151</link><pubDate>2010-08-24</pubDate></item><item><title>Fast Electron Paramagnetic Resonance Imaging (EPRI) Using CW-EPR Spectrometer with Sinusoidal Rapid-Scan and Digital Signal Processing</title><description><![CDATA[Electron Paramagnetic Resonance (EPR) Imaging is an indispensable tool that may be applied to a variety of disciplines for evaluation of chemical species having unpaired electrons such as free radicals and transition metal ions. In Continuous Wave (CW)-EPR the sample is continuously irradiated with weak RF radiation while sweeping the magnetic field relatively slowly. Existing CW-EPR techniques utilize a signal detection method known as phase-sensitive detection which results in data acquisition times that are too long for in vivo applications. The present technology represents significant improvements on conventional CW-EPR.

The subject technology includes three approaches to collecting image data with increased spatial, temporal and spectral resolution and improved sensitivity. Spectral data acquisition is performed by a direct detection strategy involving mixing a signal to base-band and acquiring data with a fast-digitizer. Projection data is acquired using a sinusoidal magnetic field sweep under gradient magnetic fields. Data collection times are decreased with the utility of rotating gradients.

Further improvement to the present technology includes optimized DSP (digital signal processing) transmit and receive systems that decrease the analog background noise and allow optimizing the extent of signal averaging for improved image quality.

Increased speed and sensitivity make CW-EPR a potentially useful and complementary tool to proton Magnetic Resonance Imaging for in vivo imaging. The presently described improvements to CW-EPR will allow changes of blood perfusion and oxygenation in tumors to be observed in nearly real-time, while improved resolution will permit angiogenesis in and around tumors to be monitored in a non-invasive manner. Additionally, rapid scan imaging provides excellent temporal resolution and will help quantify pharmaco-kinetics and metabolic degradation kinetics of bioactive and redox sensitive free radicals such as nitroxides.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1485</link><pubDate>2010-08-23</pubDate></item><item><title>P2Y1 Receptor Antagonists</title><description><![CDATA[NIH inventors have developed P2Y1 receptor antagonists ((N)-Methanocarba 2'-Deoxyadenosine 3', 5'-Bisphosphate Analogues) for inhibition of platelet aggregation and treatment of clotting conditions.  On the platelet surface, simultaneous activation of the P2Y1 and P2Y12 receptors by ADP induces aggregation. The P2Y1-mediated response is associated with the initial shape change and rapid aggregation, and the P2Y12 receptor is associated with amplification of the aggregation. P2Y12 receptor antagonists are both in clinical use and under development as antithrombotic agents. Potent and selective P2Y1 receptor antagonists, such as the conformationally locked methanocarba nucleotide MRS2500 1 (Ki 0.79 nM), have been designed and shown to have promise in preclinical studies as antithrombotic agents. This novel drug concept is also supported by studies of mice in which the P2Y1 receptor has been genetically deleted, wherein the initiation of clotting events is markedly impaired.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2042</link><pubDate>2010-08-23</pubDate></item><item><title>Novel Drugs for the Treatment of Schizophrenia</title><description><![CDATA[Because psychosis and cognitive decline are among the most common debilitating afflictions of humans, the search for new treatments is very important and timely.

Researchers at the NIH have found that genetic variations on the PIK3CD gene are associated with schizophrenia in Caucasian and African American families and can affect normal human cognition functions such as memory, IQ and executive cognition. The inventors have shown that an inhibitor of the phosphatidylinositol 3-kinase p110 delta (PIK3CD) enzyme, which is encoded by the PIK3CD gene, significantly improves a migratory response that is critically impaired in schizophrenic patients. This drug, as well as other PIK3CD inhibitors, could provide effective treatments of psychosis and cognitive decline.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2148</link><pubDate>2010-08-23</pubDate></item><item><title>Method of Producing Immortalized Primary Human Keratinocytes for HPV Investigation, Testing of Therapeutics, and Skin Graft Generation</title><description><![CDATA[One of the major limitations of using cultured keratinocytes for research studies is that primary keratinocytes senesce after a few passages. Keratinocytes from specific anatomical sites are also difficult to culture. Scientists at the NIH have demonstrated that primary keratinocytes, from several anatomical sites, when treated with a small-molecule inhibitor of the ROCK protein maintain a proliferative state and become immortal without genetic modification to the cells. Keratinocytes are also the host cells for human papillomaviruses (HPVs) and other viruses and this technology enables the study of those viruses that do not immortalize cells. In addition, this technology may enhance the quantity of material available for skin grafts, as current grafting techniques are limited by the amount of donor material immediately available. Thus, this technology may provide an ideal model environment for producing large quantities of both normal and diseased primary human keratinocytes from small numbers of primary cells from individual hosts or anatomical sites for research purposes, testing of therapeutics, skin graft generation and HPV investigation.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2149</link><pubDate>2010-08-23</pubDate></item><item><title>System and Method for Producing Nondiffracting Light Sheets that Improves the Performance of Selective Plane Illumination Microscopy (SPIM)</title><description><![CDATA[The technology offered for licensing relates to a system and method of producing nondiffracting beams of light that spatially overlap, but do not interfere with each other when intersecting the detection plane of an optical arrangement. The system includes an illumination source (i.e. ultrafast laser) for transmitting a beam of light through the optical arrangement that includes a diffraction grating for diffracting the light beam to produce beams of light having different wavelengths, which are then passed through an annular aperture that transforms the beams of light into nondiffracting beams having different wavelengths. The method can be readily utilized in Selective Plane Illumination Microscopy (SPIM), a system that provides optical sectioning of a sample that is labeled with fluorescent dyes. SPIM can provide quantitative three-dimensional maps of the distribution of a flurophore within the sample with high spatiotemporal resolution and an excellent signal-to-noise ratio. The standard SPIM technique however produces nonuniform axial resolution, which is caused by the diffraction of the laser beam through the sample, causing degradation in the optical sectioning, and forcing a compromise between field of view and axial resolution. Techniques for decoupling field of view and axial resolution have previously utilized nondiffracting beams (e.g. Bessel beams) for sample illumination. The resulting interference from multiple nondiffracting beams degrades the quality of optical sectioning and the quality of the image. The present technology utilizing nondiffracting noninterfering beams is intended to alleviate the problems associated with the currently used SPIM techniques.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2150</link><pubDate>2010-08-23</pubDate></item><item><title>Tempol: A Commercially Available Nitroxide as Cancer Therapeutics</title><description><![CDATA[The invention is the discovery that a commercially available stable nitroxide, namely TEMPOL can effectively reduce the level of hypoxia-inducible transcription factor (HIF)-2alpha.  Elevated HIF-2alpha is associated with clear cell kidney cancer characterized by mutation of the VHL tumor suppressor gene and with many other cancers.  Therefore, TEMPOL can potentially be developed into a cancer drug to treat patients with elevated HIF-2alpha, whether due to compromised VHL function or not.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2152</link><pubDate>2010-08-23</pubDate></item><item><title>Melanocyte Pigmentation or Proliferation with Neuregulin:  Compositions and Methods to Treat Skin Disorders, Including Skin Cancer</title><description><![CDATA[Human skin pigmentation is regulated by complex and intricate interactions among melanocytes and keratinocytes in the epidermis and fibroblasts in the dermis.  A number of factors secreted from keratinocytes and/or from fibroblasts have been shown to be involved in regulating skin pigmentation after UV exposure.  NIH investigators have previously demonstrated that the less pigmented and thicker skin on the palms and soles is regulated by underlying fibroblasts in those areas, specifically via a secreted factor (DKK1) that modulates Wnt signaling.  Now, using microarray analysis to compare gene expression patterns in 15 different primary dermal fibroblast populations derived from the dorsal trunk skin of three different skin phototypes (I, III and VI), these investigators have identified a number of genes that differ dramatically in expression.  One among them, neuregulin 1 (NRG-1), secreted by fibroblasts derived from dark skin, effectively increases the pigmentation of melanocytes in tissue culture and in an artificial skin model and regulates their growth, suggesting it is one of the  major factors determining human skin color.  NRG-l was observed to be highly expressed by fibroblasts derived from darker skin.  NIH investigators believe that NRG-1 increases the proliferation of human melanocytes via the phosphorylation of Akt.  These results suggest a potential role for NRG-1 in regulating constitutive human skin color and perhaps its dysfunction in pigmentary skin diseases.  Based on these observations, NIH investigators are currently developing compositions and methods of modulating pigmentation and proliferation of a melanocyte to prevent or treat skin disorders, including skin cancer.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2146</link><pubDate>2010-08-19</pubDate></item><item><title>Matrix Metalloproteinase-9 Blade-1 Region Peptides: Use as Cell Migration Modulators</title><description><![CDATA[Matrix metalloproteinase-9 (MMP-9) is an enzyme integrally involved in many normal physiological processes that require degradation and remodeling of the extracellular matrix, such as cell migration and invasion, wound repair, bone remodeling, angiogenesis, and embryonic growth.  MMP-9 is shown to be involved in the progression of several diseases including many cancers, cardiovascular diseases, CNS diseases, respiratory diseases, and arthritis.  In cancer, MMP-9 is thought to promote growth, migration, and spread of cancer cells by catalyzing the degradation of extracellular matrix proteins, releasing bound growth factors, and allowing cancer cells to escape from the primary tumor.

NIH inventors have discovered that specific polypeptides corresponding to Blade-1 region of MMP-9 hemopexin domain can stimulate migration of cells, specifically the migration of cells expressing beta1 integrin. The present technology can be used to develop novel therapeutic candidates for the prevention and treatment of human disease conditions mediated by MMP-9 promoted cell migration, e.g., cancer, inflammation, fibrotic diseases, cardiovascular diseases, CNS diseases, respiratory diseases, angiogenesis and arthritis.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2145</link><pubDate>2010-08-17</pubDate></item><item><title>Transforming Growth Factor Beta-1 (TGF-beta1) Transgenic Mouse Model</title><description><![CDATA[Transforming Growth Factor-beta1 (TGF-beta1) is a multifunctional cytokine that is involved in many physiological processes such as immune regulation, cell proliferation, angiogenesis, apoptosis, and extracellular matrix deposition. Overexpression of activated TGF-beta1 signaling pathway is known to play a role in many disease processes, such as inflammation, fibrosis and tumor metastasis.

NIH inventors have developed a transgenic mouse model, designated beta1glo, which permits conditional, gene-specific overexpression of TGF-beta1.  The model features a TGF-beta1 transgene for which expression is blocked by a floxed enhanced green fluorescent protein (EGFP) gene downstream of the promoter.  Excision of the EGFP gene by Cre recombinase allows expression of TGF-beta1.  Thus, these mice may be cross-bred with a variety of Cre transgenic mouse lines in order to study the role of TGF-beta1 in targeted organ systems and tissues.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2147</link><pubDate>2010-08-17</pubDate></item><item><title>A Fertility Test to Detect Ovarian Autoimmune Disease Using Human Recombinant MATER Protein</title><description><![CDATA[The inventors have identified MATER, a gene that plays an important role in fertility, and have shown that antibodies against MATER protein are detected at higher frequencies in women experiencing infertility and irregular menstrual periods than in healthy women.  The discovery of MATER as an important factor in autoimmune-mediated ovarian dysfunction will facilitate diagnosis and treatment of these disorders.   In addition to its critical role in ovarian autoimmunity, the inventors have also discovered that the MATER gene plays an essential role in embryonic development.

The invention discloses the MATER gene, MATER protein and MATER-specific antibodies.  Also disclosed are methods and kits for evaluating female infertility through detection of an abnormal autoimmune response, an abnormal MATER gene, or abnormal MATER protein expression.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=692</link><pubDate>2010-08-17</pubDate></item><item><title>Species-Independent A3 Adenosine Receptor Agonists Which May Be Useful for Treating Ischemia, Controlling Inflammation, and Regulating Cell Proliferation</title><description><![CDATA[This invention claims species-independent agonists of A3AR, specifically (N)-methanocarba adenine nucleosides and pharmaceutical compositions comprising such nucleosides.  The A3 adenosine receptor (A3AR) subtype has been linked with helping protect the heart from ischemia, controlling inflammation, and regulating cell proliferation.  Agonists of the human A3AR subtype have been developed that are also selective for the mouse A3AR while retaining selectivity for the human receptor.  This solves a problem for clinical development because animal model testing is important for pre-clinical validation of drug function.  Novel agonists have been made that exhibit as much as 6000x selectivity for A3 versus A1 in humans while retaining at least 400x selectivity for A3 versus A1 in mice.  In addition, the molecules of the invention exhibit very low nanomolar affinity. This innovation will not only facilitate moving A3 agonists into the clinical phase of drug development by being more amenable to animal studies, but also provide much greater selectivity in humans, and thereby potentially fewer side effects than drugs currently undergoing clinical trials.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1796</link><pubDate>2010-08-11</pubDate></item><item><title>Inflammatory Genes and MicroRNA-21 as Biomarkers for Colon Cancer Prognosis</title><description><![CDATA[Colon adenocarcinoma is the leading cause of cancer mortality world-wide and accounts for approximately 50,000 deaths annually in the United States.  Adjuvant therapies improve survival for stage III colon cancer patients; however, it remains controversial if stage II patients should be given these therapies.  Some stage II patients will benefit from therapy (such as patients with undetectable micro-metastases where surgery will not be curative); but therapy for others will harm quality of life with little therapeutic benefit (such as patients where surgery removed all cancerous tissue and therefore do not need additional therapy).  Thus, there is a need to for biomarkers capable of accurately identifying high risk, stage II patients that are suitable for therapeutic intervention.

The investigators have identified an inflammatory gene and microRNA biomarker portfolio that can predict aggressive colon cancer, colon cancer patient survival, and patients that are candidates for adjuvant therapy.  These biomarkers provide clinicians with a powerful tool to diagnose colon cancer patients and chose effective treatment methods.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1975</link><pubDate>2010-08-11</pubDate></item><item><title>A Novel Scaffold for Multivalent Display of Ligands</title><description><![CDATA[Multivalent interactions are important in cell attachment, wound healing and immune responses. Such interactions are associated with cancer metastasis, blood clotting and the generation of antibodies from a vaccination. Mimicking multivalent interactions on a synthetic scaffold is challenging especially when large numbers of ligands (such as 5 or more) need to be displayed.  There are numerous synthetic scaffolds that have been developed, but there are significant limitations that remain.

Scientists at the NIH have designed a novel multivalent scaffold that can display anywhere from 1 to 200 ligands. This system allows different types of ligands to be displayed in a controlled, spatially-addressable manner. This system uses peptide nucleic acids (PNAs) containing gamma-substituted side chains. PNAs are synthetic molecules that possess the bases derived from DNA. This invention could revolutionize the way in which multivalent display is used in research as well as help make vaccinations or prevent disease.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2142</link><pubDate>2010-08-11</pubDate></item><item><title>N-Methanocarba Adenosine Derivatives and Their Dendrimer Conjugates as A3 Receptor Agonists</title><description><![CDATA[This technology relates to specific (N)-methanocarba adenine nucleosides that have been developed and dendrimers that connect these compounds to create molecules with multiple targets.  Dendrimers are essentially repeated molecular branches presenting the core receptor-binding molecules. The compounds synthesized function as agonists and antagonists of a receptor of the G-protein coupled receptor (GPCR) superfamily.  In particular, the receptors of interest for this invention include A3 adenosine receptors and agonists and antagonists of P2Y receptors, such as P2Y1 and P2Y14.

Dendrimer conjugates may have one or more advantages, such as increased solubility, reduced toxicity, and improved pharmacokinetic properties.  They can also be used to connect other types of molecules without affecting the agonist or antagonists properties.  For instance, molecules such as those used for imaging or tracing can be added.  Dendrimers can also be used to link more than one type of agonist or antagonist to confer multiple functionalities.  This technology provides a novel mechanism to treat a number of disorders related to dysregulation of A3 adenosine receptors.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2143</link><pubDate>2010-08-11</pubDate></item><item><title>Glioblastoma Diagnostics and Therapeutics</title><description><![CDATA[Investigators at the NIH have discovered an Anti-TNF Induced Apoptosis (ATIA) protein, which protects cells against apoptosis.  ATIA is highly expressed in glioblastoma and astrocytomas and its inhibition results in increased cell sensitivity to TNF-related apoptosis-inducing ligand induced cell death.  Hence, ATIA assays may enable clinicians to effectively stratify patients for appropriate treatment.  ATIA exists in a soluble form that can be detected in culture medium of ATIA expressing cells indicating it could be used to develop a non-invasive, blood based diagnostic test such as an ELISA.  Glioblastomas and astrocytomas can be diagnosed via MRI and CT scans; however, these scans cannot detect tumor type, i.e. glioblastoma vs. medulloblastoma. The investigators found that ATIA is induced in cells under hypoxia conditions. More importantly, knockdown of ATIA in human glioblastoma cells renders cells to apoptosis under hypoxia conditions. Therefore, ATIA is a potential novel therapeutic target for treating human glioblastoma.

Glioblastoma arise from astrocytes, cells that provide neurons structural and metabolic support.  Glioblastomas account for twenty percent of primary brain tumors and fifty percent of astrocytomas.  These indications are designated as rare diseases as there is an annual 2-3 newly diagnosed cases of glioblastoma per 100,000 people in the United States whereas the astrocytoma incidence rate is 1.22 cases per 100,000 for individuals aged 0-19 years in the United States.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2144</link><pubDate>2010-08-11</pubDate></item><item><title>Adoptive Immunotherapy with T Lymphocytes Engineered for Enhanced Survival</title><description><![CDATA[Available for licensing is a composition, comprising genetically engineered lymphocytes, transduced to express elevated levels of cytokine proteins.  This technology is useful for improving cellular adoptive immunotherapies to treat a range of infectious diseases and cancers.

Adoptive immunotherapy has repeatedly been shown to be useful in the treatment of patients with metastatic melanoma.  However, clinical efficacy of this treatment is limited by the short-lived survival of the transferred, autologous, antigen-specific T cells.  It would be desirable to genetically modify effector cells to provide not only enhanced effector cell survival, but also desired antigen specificity, and improved function, and safety.  The current technology provides a method address this desire, by genetically modifying lymphocytes using retroviral vectors.

Specifically, isolated autologous T lymphocytes can be transformed with polynucleotides encoding endogenous cytokines, for example IL-7 or IL-15.  IL-15-transduced lymphocyte cultures demonstrate prolonged in vitro persistence.  In addition, T cells can be transduced to express not only cytokines but also T cell receptors to confer specificity for certain antigens.  Recent data showed that human T lymphocytes engineered to express a murine anti-human p53 T cell receptor can recognize tumor cell lines, as well as fresh human tumors, and are able to kill p53-expressing human tumor cells.

Also provided in the invention are methods for treating patients with transformed lymphocytes as part of adoptive immunotherapy.  Applications of this technology beyond cancer include the potential use of cytokine expressing cells in treating infectious and autoimmune diseases and vaccination.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1313</link><pubDate>2010-08-04</pubDate></item><item><title>Novel Peptides to a Melanoma Antigen and Their Use in Diagnostic and Therapeutic Methods</title><description><![CDATA[Various tumor-associated antigens are recognized by T cells, thereby eliciting an immune response.  Among these tumor-associated antigens is gp100, which along with several other tumor antigens identified to date is associated with malignant melanoma.  Most of the gp100 peptide epitopes identified to date are HLA-A2 (MHC Class I) restricted.

The current invention embodies the identification of a novel HLA-DRB1*0701 (MHC Class II) restricted epitope of gp100.  As 16-28% of the population is HLA-DRB1*0701 positive, this peptide could represent a potential immunotherapeutic vaccine for use against melanoma in a significant percentage of the patient population.  In addition, the current invention represents only the second gp100 peptide identified to date that is capable of eliciting a CD4+ helper T cell response.  It is believed that administration of a peptide capable of eliciting a CD4+ T cell response may be required in order to upregulate a CD8+ T cell response against a Class I-restricted peptide.  The identification of an immunogenic Class II-restricted epitope therefore could be of particular importance not only as an immunotherapeutic vaccine in and of itself, but also for use in a vaccination protocol in combination with an immunogenic Class I-restricted peptide.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=557</link><pubDate>2010-08-04</pubDate></item><item><title>Transgenic Mouse Model for Lupus and Other Autoimmune Diseases</title><description><![CDATA[The inventors have developed a series of transgenic mice that overexpress Toll-Like Receptor 7 (TLR7) at different levels.  Overexpression of TLR7 in these mice results in a lupus-like syndrome, the intensity of which correlates with the level of overexpression.  As the pathology in these mice results from the overexpression of a single gene, it represents a superior model for lupus and other autoimmune diseases compared to other existing mouse models that dysregulate multiple genes to achieve the same pathologic syndrome. 

Two strains are currently available.  The TLR7.Tg1 strain overexpresses TLR7 at approximately 16 times the wild-type level.  The TLR7.Tg6 strain overexpresses TLR7 at approximately 4 times the level of a wild-type mouse; additionally, the transgene for this strain is located on the Y chromosome, which would be advantageous for cross-breeding to other mouse lines.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1582</link><pubDate>2010-08-03</pubDate></item><item><title>Use of Immunosuppressive Agents for Treatment of Age-related Macular Degeneration (AMD) and Diabetic Retinopathy</title><description><![CDATA[AMD belongs to a group of disorders in which the immune system may play an important role.  This invention discloses that patients with AMD gain additional therapeutic benefit from combination treatment of immunosuppressive agents and standard-of-care in comparison to standard-of-care alone.  This invention slows the progression of choroidal neovascularization (CNV) and may have implications for related pathologies, including diabetic retinopathy.  Clinical data from a small, randomized pilot clinical trial are available.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2130</link><pubDate>2010-08-03</pubDate></item><item><title>Software System with Applications in Clinical Prognosis, Personalized Medicine and Clinical Research</title><description><![CDATA[Available for licensing is software that can provide prognostic information for different diseases and in particular for cancer. The software can determine whether a particular genotype has a significant association with survival time for an individual receiving treatment. For example, it can determine if a specific genetic pattern is associated with an increased or decreased time to recurrence of a particular type of cancer for patients on a given treatment regimen.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2136</link><pubDate>2010-08-03</pubDate></item><item><title>Software for Accurate Segmentation of Cell Nuclei in Breast Tissue</title><description><![CDATA[Automatic segmentation of cell nuclei is critical in several high-throughput cytometry and pathology applications (1), such as spatial analysis of genetic loci by fluorescence in situ hybridization ("FISH"), whereas manual segmentation is laborious (2). Current automated segmentation methods have varying performance in the presence of distortions introduced during sample preparation, non-uniform illumination, clustering of the individual objects of interest (cells or cell nuclei), and seldom assess boundary accuracy.

Researchers at the National Cancer Institute-Frederick, NIH, have developed an automatic algorithm to segment cell nuclei (3) and FISH signals from two-dimensional images of breast tissue. This automated system integrates a series of advanced image processing methods to overcome the delays inherent to current manual methods for segmenting (delineating) individual cell nuclei in tissue samples.  The system automatically selects a subset of nuclei that with high likelihood are accurately segmented. This system has been validated using both simulated and actual datasets that have been accurately analyzed by manual methods.  The system generalizes to independent analysis of many spatial parameters useful for studying spatial gene positioning in interphase nuclei, and potentially has a wide range of diagnostic pathology, cytological and high throughput screening applications.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2137</link><pubDate>2010-08-03</pubDate></item><item><title>Use of Cucurbitacins and Withanolides for the Treatment of Cancer</title><description><![CDATA[Certain members of the cucurbitacin and Withanolide family have been identified that can sensitize some tumor cell lines to cell death (apoptosis) on subsequent exposure of the cells to pro-apoptotic receptor agonists (PARAS) of the TRAIL "death receptors". These PARAS include TRAIL itself, and agonist antibodies to two of its receptors death receptor-4 (DR4 or TRAIL-R1) and death receptor 5 (DR5, TRAIL-R2).

The protein TRAIL has a very interesting characteristic that it can preferentially cause death of cancer cells whereas normal non-transformed cells are unaffected.  Thus use of TRAIL or agonist antibodies to its so-called "death receptors" has been a current focus in cancer therapy.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2138</link><pubDate>2010-08-03</pubDate></item><item><title>Nitroxyl (HNO) Releasing Compounds and Uses Thereof in Treating Diseases</title><description><![CDATA[This technology discloses HNO releasing compounds and methods of treating various diseases with such compounds.  HNO has recently emerged as a prospective pharmacological agent.  Studies of the chemistry of HNO have led to an understanding that HNO is vastly different from nitric oxide (NO), the one-electron oxidation product of HNO.  HNO displays unique cardiovascular properties and has been shown to have positive effects in failing hearts without changing heart rate.  HNO has also been shown to have beneficial effects in ischemia reperfusion injury.  In addition to the cardiovascular effects observed, HNO has shown initial promise in the realm of cancer therapy.  HNO has been demonstrated to inhibit a key glycolytic enzyme. Due to the Warburg effect, inhibiting glycolysis is an attractive target for inhibiting tumor proliferation.  HNO has recently been shown to inhibit tumor proliferation in mouse xenografts.  Additionally, HNO inhibits tumor angiogenesis and induces cancer cell apoptosis.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2139</link><pubDate>2010-08-03</pubDate></item><item><title>Immortalized Human Bronchial Epithelial Cell Line</title><description><![CDATA[Normal cells can be cultured in vitro for a limited period of time before they exhibit a "crisis" or senescence, wherein they display abnormal cell morphology and significant reduction or cessation of cell proliferation.  Investigators at the National Cancer Institute developed immortalized cell line by isolating bronchial epithelial cells from non-cancerous individuals and subsequent infection with an adenovirus 12-SV40 virus hybrid.  Unlike normal cells, the immortalized cells be cultured continuously in vitro in suitable medium and retain features of normal human bronchial epithelial cells, including the absence of invasive behavior in vitro or in vivo.  These cells can also be transfected with oncogenes and used as a model for multistage carcinogenesis, or employed to assay a biological or chemical agent's ability to induce differentiation and carcinogenesis as well as test potential chemotherapeutic agents.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2141</link><pubDate>2010-08-03</pubDate></item><item><title>Use of Anthrax Lethal Factor to Treat Cancer and Screening Methods for MAPK Kinase Protease Activity</title><description><![CDATA[Anthrax toxin, produced by Bacillus anthracis, is composed of three proteins; protective antigen (PA), edema factor (EF), and lethal factor (LF). PA by itself has little or no toxic effect upon cells, but serves to bind cell surface receptors and mediate the entry of EF and LF into the cell. EF has been identified as an adenylate cyclase and together with PA forms a toxin (edema toxin; EdTx) which can induce edema formation when injected subcutaneously. LF and PA together form a toxin (lethal toxin; LeTx) which can cause rapid lysis of certain macrophage-derived cell lines in vitro as well as death when injected intravenously. 

Indirect evidence had suggested that LF was a metalloprotease. However, the intracellular target of LF remained unknown until recently when NIH scientists discovered that LF proteolytically inactivates mitogen activated protein kinase kinase 1 and 2 (MAPKK1, 2). Using oocytes of the frog Xenopus laevis as well as tumor derived NIH3T3 (490) cells expressing an effector domain mutant form of the human V12HaRas oncogene these scientists demonstrated that LF induced proteolysis of MAPKK 1 and 2, resulting in their irreversible inactivation. MAPKK 1 and 2 are components of the mitogen activated protein kinase (MAPK) signal transduction pathway, an evolutionarily conserved pathway that controls cell proliferation and differentiation in response to extracellular signals and also plays a crucial role in regulating oocyte meiotic maturation. Further, the MAPK pathway has been shown to be constitutively activated in many primary human as well as in tumor-derived cell lines. Consistent with this, treatment of V12Ha-Ras transformed NIH 3T3 cells with LeTx inhibits cell proliferation and causes their reversion to a non-transformed phenotype. 

This invention specifically relates to in vitro and ex vivo methods of screening for modulators, homologues, and mimetics of LF mitogen activated protein kinase kinase (MAPKK) protease activity. Applications for this technology could be:

A novel tool (LF) for the study of the cellular role of the MAPK pathway in normal or tumor cells.
Investigation of LF for developing inhibitors for cancer therapy. By analyzing structural-functional relationships, additional compounds with improved specificity, increased potency, and reduced toxicity can be generated. Mimetics which block MAPKK activity or the determination of mechanisms of regulation of proteases that target MAPKK at or near the same site targeted by LF could be developed.
A protease-based assay for LF by using a peptide to test for LF cleavage. There is no commercial test for anthrax. This assay could be used for testing soldiers for anthrax exposure. Characterization of the interaction between LF and MAPKK at the amino acid level may lead to the generation of inhibitors which may prove useful in treating anthrax.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=408</link><pubDate>2010-08-02</pubDate></item><item><title>Rapid Methods for Human Artificial Chromosome (HAC) Formation</title><description><![CDATA[Human artificial chromosomes (HACs) provide a unique opportunity to develop a new generation of vectors for therapeutic use as gene expression and delivery systems.  The advantages of a high-capacity, non-integrating chromosome-based vector capable of autonomous replication and long-term gene expression are evident for potential use in gene therapy and this area is one of active research.  In particular, the generation of a functional centromere (a complex structure needed for segregation at cell division) has been recognized as key in the production of synthetic chromosomes.  However, a typical human centromere extends over many millions of base pairs containing mainly alphoid satellite DNA (171 bp repeating units) organized into higher order repeats (HORs), which have been difficult to fully characterize or modify readily.  There remains a need to elucidate the structural requirements of alphoid DNA arrays for efficient de novo assembly of centromere structure in order to construct HAC vectors able to carry intact mammalian genes capable of fully regulated gene expression and which can be stably maintained in the host nucleus for use in gene therapy.

The group of Dr. Larionov at the NCI and colleagues have recently developed a  novel strategy to rapidly construct large synthetic alphoid DNA arrays with a predetermined structure by in vivo recombination in yeast.  The invention is a two step method involving 1) rolling-circle amplification (RCA) of a short alphoid DNA multimer (e.g. a dimer) and 2) subsequent assembly of the amplified fragments by in vivo homologous recombination during transformation with a Transformation-Associated Recombination targeting vector (TAR-NV) into yeast cells.  This method or Recombinational Amplification of Repeats (RAR) has been used to construct sets of different synthetic alphoid DNA arrays varying in size from 30 to 120 kb which were shown to be competent in HAC formation.  Thus, these long arrays are engineered centromere-like regions that permit construction of mammalian artificial chromosomes with a predefined centromeric region structure.  As any nucleotide can be easily changed into an alphoid dimer before its amplification, this new system is optimal for identifying the critical regions of the alphoid repeat for de novo centromere seeding.

The Mammalian Artificial Chromosome Portfolio [HHS Ref. No. E-128-2005/0-US-01 and HHS Ref. No. E-253-2000/0-US-03], including methods of generating engineered centromeric sequences, mammalian artificial chromosomes and methods of their use is available for licensing and will be of direct use to those interested in vectors providing long-term regulated expression of genes used in therapy for human disease.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1315</link><pubDate>2010-07-30</pubDate></item><item><title>The Use of Recombinant Cholera Toxin-B for the Treatment of Inflammatory Bowel Disease</title><description><![CDATA[The present invention provides methods of treating inflammatory bowel disease in a subject, comprising administering to the subject an effective amount of cholera toxin subunit B (CT-B).  In particular, the present invention provides methods of decreasing the activity of interferon-gamma in a subject, decreasing the activity of IL-12 in a subject, and treating or preventing a Th1 T-cell mediated autoimmune disorder.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2135</link><pubDate>2010-07-16</pubDate></item><item><title>Treatments for Smith-Lemli-Opitz Syndrome and Other Disorders of Cholesterol Biosynthesis</title><description><![CDATA[This technology provides methods for treating Smith-Lemli-Opitz Syndrome and other disorders of cholesterol biosynthesis.

Smith-Lemli-Opitz Syndrome (SLOS) is an autosomal recessive disorder caused by an inborn error of cholesterol biosynthesis.  It affects an estimated one in 20,000 to 60,000 newborns, and is most prevalent in Caucasians of Central European ancestry.  It is characterized by distinctive facial features, microcephaly, mental retardation or learning disabilities, and behavioral problems, as well as malformations in many parts of the body, such as the heart, lungs, kidneys, gastrointestinal tract, and genitalia.  However, the clinical manifestations of this disease can vary widely, ranging from relatively moderate symptoms to profoundly severe and life-threatening symptoms.  At least 95% of SLOS patients present with some degree of mental retardation and learning disability.

Biochemically, SLOS is caused by disruption of the DHCR7 gene, which is responsible for the final step in the production of cholesterol; this results in low cholesterol levels and an accumulation of toxic byproducts of cholesterol biosynthesis in the blood, nervous system, and other tissues.  Supplementary dietary cholesterol is provided to SLOS patients, but is often of limited clinical benefit; because levels of byproducts remain high, they may interfere with the uptake of free cholesterol.

Although some of the behavioral and learning problems are due to developmental problems, a portion of these symptoms are likely due to a biochemical disturbance.  That biochemical disturbance is potentially treatable.

In their recent work, the inventors have discovered that the accumulation in SLOS cells of the cholesterol precursor 7-DHC causes abnormal sphingolipid storage and transport, resulting in a cellular phenotype similar to that observed in the lysosomal storage disease Niemann-Pick type C (NPC).  They have also discovered that treatment with inhibitors of sphingolipid biosynthesis corrects these abnormalities, and thus such inhibitors are of potential therapeutic benefit for the treatment of SLOS, as well as for other diseases exhibiting similar defects in sphingolipid trafficking.

This technology claims compounds that inhibit sphingolipid biosynthesis for use in treating diseases which have a secondary Niemann-Pick type C disease-like cellular phenotype, including SLOS, as well as methods of treatment and pharmaceutical compositions.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2134</link><pubDate>2010-07-13</pubDate></item><item><title>Microwave-Assisted Freeze Substitution of Biological and Biomedical Samples</title><description><![CDATA[Freeze substitution fixation (FS) of hydrated samples frozen in vitreous ice provides exceptional preservation of structure for light and electron microscopy, and enables immunological detection of thermo-labile antigens that otherwise are damaged/destroyed by processing at ambient or elevated temperatures.  Its use as a research tool or in clinical pathology has, however, been limited by the relatively lengthy periods required for passive diffusion of fixatives and organic solvents into the frozen hydrated material.

The invention utilizes controlled microwave (MW) irradiation to accelerate the FS process; and comprises systems, devices and methods for microwave-assisted processing of samples under cryo-conditions.  The entire MWFS procedure has been accomplished in less than 4 hours as compared to the approximately 2-5 days required for FS.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1892</link><pubDate>2010-07-12</pubDate></item><item><title>Mouse Model of Individual Unresponsive to Interferon</title><description><![CDATA[NIAID has developed a mouse model that produces very high levels of Interferon-alpha-receptor 2 (IFNAR2), both in liver cells and free-floating in serum. 

Chronic co-infection of HIV and hepatitis C virus (HCV) is associated with increased overall morbidity and mortality compared to those infected with just one virus.  Recent data further suggests that co-infection is also associated with a more rapid progression of liver disease, higher HCV RNA viral levels, decreased cure rate of HCV, and increased toxicities of anti-HCV therapy.  Finally, clinical trials have shown that many patients infected with both viruses do not respond to Interferon-based therapy.  Research strongly suggests that non-responding patients have an increased level of a free-floating form of IFNAR2, which could block Interferon activity. 

Resistance to Interferon therapy also occurs in other diseases, such as autoimmune diseases (e.g., lupus, scleroderma, psoriasis, vasculitis) and certain forms of cancer (e.g., Kaposi?s sarcoma, follicular lymphoma).  The various means by which resistance arises is currently being researched.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1967</link><pubDate>2010-07-12</pubDate></item><item><title>Topical Formulation of Histone Deacetylase (HDAC) Inhibitors: Treatments for Cancer and Immunological Skin Disorders</title><description><![CDATA[This technology relates to topical formulations of Histone Deacetylase (HDAC) inhibitors (HDIs) that can be used to treat cancers such as cutaneous T-cell lymphoma (CTCL) and skin disorders such as lupus, contact dermatitis, and drug eruptions which are associated with malignant or autoreactive lymphocytes from the immune system.  HDIs, such as depsipeptide, have been demonstrated to be effective against CTCL when administered internally but a topical preparation may be more useful for treatment at earlier stages of the disease.

HDIs are molecules that inhibit the activity of a group of enzymes that remove small chemical groups called acetyl groups from many different proteins, including proteins that regulate gene expression.  By altering the acetylation of these proteins, HDAC inhibitors can induce tumor cell differentiation, cell cycle arrest, and cell death.  A variety of chemically distinct molecules exhibit HDAC inhibitory activity and their potential as therapeutics for cancer and other indications is being investigated.  The HDI depsipeptide is a cyclical peptide derived from a bacterium and is indicated as a second line treatment for CTCL through intravenous administration.  Development of a topical preparation of depsipeptide and/or other HDAC inhibitors may help reduce their toxicity and increase their effectiveness in treating CTCL, other cancers, as well as other diseases.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2098</link><pubDate>2010-07-12</pubDate></item><item><title>A Method of Measuring Ultraviolet A (UVA) Protection in Sunscreen Products</title><description><![CDATA[There are different types of ultraviolet (UV) rays in sunlight.  UVB radiation causes redness (erythema) or sunburn.  While UVA radiation, which absorbs deep into the skin, causes more long-term effects such as wrinkles, skin aging and skin cancer.

Effective sunscreens are expected to block both UVA and UVB radiation.  The Sun Protection Factor (SPF) label found on all over-the-counter sunscreen products is a better measure for UVB protection than UVA protection.  Currently, there is no standard in vivo test to determine the amount of UVA protection in sunscreen products, despite the fact that many products are advertised as effectively blocking both UVA and UVB radiation.

This invention describes sets of genes useful for measuring UVA exposure in human skin and assessing sunscreen products for their ability to block UVA radiation.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2107</link><pubDate>2010-07-12</pubDate></item><item><title>UOK171, A Spontaneous Clear Cell Type Renal Cell Carcinoma (ccRCC) Human Cell Line Derived from a Surgically Removed Tumor</title><description><![CDATA[Scientists at the National Institutes of Health (NIH) have developed a renal cell carcinoma (RCC) cell line designated UOK171 from the resected tumor of a patient diagnosed with stage IV high nuclear grade clear cell type renal cell carcinoma (ccRCC). The UOK171 cell line was immortalized spontaneously by mincing the resected tumor into pieces followed by propagation of the cells over more than twenty generations. One of the most prominent characteristics of this cell line is its intact, nonmutated von Hippel-Lindau (VHL) tumor suppressor gene. In the majority of sporadic and hereditary ccRCC cases, the VHL gene is functionally disrupted due to hypermethylation or the gene is completely lost. Thus, the UOK171 cell line is very useful as a positive control for VHL gene expression in studies of the genetic and molecular mechanisms underlying advanced ccRCC, a disease for which there is no effective treatment. Specifically, this cell line has been used as a non-methylated control cell line in studying the effects of 5-Aza-dCyd and Zebularine on VHL re-expression from methylated-VHL cell line models. These agents do not affect the methylation status of the VHL gene in UOK171. This cell line also exhibits decreased fibroblast growth factor 5 (FGF5) expression, unbalanced chromosome 3 translocations, translocations involving chromosome 14, the losses of chromosome 14 and 22, and chromosome structural aberration 1(8) (q10). UOK171 is also one of the 40-member cell lines in the National Cancer Institute (NCI) Urologic Oncology Branch (UOB) Tumor Cell Line Repository.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2116</link><pubDate>2010-07-12</pubDate></item><item><title>Therapeutics for the Treatment and Prevention of Atherosclerosis and Cardiovascular Disease</title><description><![CDATA[This technology consists of peptides and peptide-analogues that enhance clearance of excess cholesterol in cells and do not exhibit the cytotoxicity that has hampered development of similar potential therapeutics.

Briefly, apolipoprotein A-1 (ApoA-1) promotes cholesterol efflux from cells and its concentration is inversely correlated with atherosclerotic events.  The isolated peptidic component of ApoA-1 that acts within the cholesterol secretion pathway is therapeutic towards atherosclerosis but exhibits cytotoxic effects.  In contrast, our inventors have derivatized that ApoA-1 peptide which is both less cytotoxic and more active than the underivatized component in initial studies.  This potential therapeutic is similar to high density lipoprotein (HDL) therapy and may complement statin-mediated reduction of pro-atherogenic lipoproteins.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2129</link><pubDate>2010-07-12</pubDate></item><item><title>A Transgenic Model of Human Basal Triple Negative Breast Cancer [C3(l)-tag mice]</title><description><![CDATA[Basal triple-negative breast cancer (TNBC) is a common form of human breast cancer for which there are no specific, targeted therapies, unlike hormone-responsive or Her2+ breast cancers. TNBC has a much worse prognosis than hormone receptor + cancer and is disproportionately high in the African-American population. NIH scientists have created and characterized a transgenic model that is currently an excellent mouse model for TNBC that shares important molecular characteristics of human TNBC, making it highly useful for preclinical testing of drugs and novel therapies. This model may provide a valuable means of identifying new drugs and therapies that could be translated to human clinical trials. The mouse model also develops prostate intraepithelial neoplasia and prostate cancer, therefore has also been used for studies of prostate cancer. The studies using the mouse model may fill important public health service needs.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2131</link><pubDate>2010-07-12</pubDate></item><item><title>Improved Pepper Spray for Repellency and Incapacitation</title><description><![CDATA[Non-lethal means of temporarily incapacitating a person are greatly needed for law enforcement and for personal protection.  A common approach is to use pepper spray.  Although current pepper sprays are effective, they cause pain for excessively long periods, and could be life threatening for people who suffer from asthma and have hypersensitive airways.  This technology describes a composition for use in an aerosol or spray, that when administered, causes a painful stimulation and incapacitates a person for only a brief period. This technology may improve safety over currently available pepper sprays.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2132</link><pubDate>2010-07-12</pubDate></item><item><title>Novel Antigen for Use as Vaccine Against Nematode Infection</title><description><![CDATA[This invention describes a new vaccine against Strongyoides stercoralis, which establishes a parasitic infection that affects an estimated 100-200 million people worldwide. The potential for fatal disease associated with S. stercoralis infection and the difficulty in treating hyperinfection underscores the need for prophylactic vaccines against the disease. This vaccine uses S. stercoralis immunoreactive antigen (SsIR); a novel antigen capable of providing 70-90 % protection for mice immunized with the antigen. In addition, sera from immunized mice have also been used to effectively protect naive mice from infection.

The invention may also have potential use in diminishing allergic responses, as Strongyoides stercoralis infection has been shown to reduce the murine response to allergens. Consequently, SsIR may be used to immunize individuals and reduce the allergic response. The antigen may also be used to identify homologous antigens from other parasitic nematodes that may be important for vaccine development.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2133</link><pubDate>2010-07-12</pubDate></item><item><title>Retroviral Vectors for Selective Reversible Immortalization of Stimulus-responding Primary Cells</title><description><![CDATA[Researchers at the National Cancer Institute-Frederick, NIH, have developed a novel set of retroviral vectors and producer cell lines useful for selective reversible immortalization of primary cells (i.e. lymphocytes) that respond to a stimulus, such as a viral antigen (e.g. HIV toxoids), a tumor antigen, or a growth factor.

Derived from the murine leukemia virus (MuLV), these retroviral vectors will only infect dividing cells. Therefore, only primary cells activated by the stimulus will be infected and immortalized, thereby creating an "antigen-specific trap."

The primary cells to be immortalized can be in targeted tissue or in stimulated ex vivo culture.  The transduced cells can be expanded to large numbers without differentiating, and returned to the primary cell stage by removal of the introduced genes using a vector excision strategy.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2106</link><pubDate>2010-07-07</pubDate></item><item><title>UOK 257, the First BHD Tumor Cell Line, and UOK257-2 Wild Type FLCN-restored Renal Cell Line as In Vitro and In Vivo Models of Energy/Nutrient Sensing Through the AMPK and mTOR Signaling Pathways</title><description><![CDATA[Scientists at the National Institutes of Health (NIH) have developed a novel renal cell carcinoma (RCC) cell line designated UOK257, which was derived from the surgical kidney tissue of a patient with hereditary Birt-Hogg-Dub? (BHD) syndrome and companion cell line UOK257-2 in which FLCN expression has been restored by lentivirus infection. These cell lines harbors a germline mutation of FLCN gene (alias BHD) and displays loss of heterozygosity, can grow as xenograft in nude mice. Patients affected with BHD develop skin papules (fibrofolliculomas), lung cysts, spontaneous pneumothorax and an increased risk for bilateral multifocal renal tumors.  Loss of both copies of the FLCN gene has been documented in BHD renal tumors; however, the molecular mechanisms by which inactivation of the encoded protein, folliculin, leads to the BHD phenotype are currently unknown. They have developed an important research tool for in vitro folliculin functional studies.  The companion cell line will be extremely useful for comparative biochemical analyses of cell culture systems in which the FLCN gene is either expressed or inactivated, including identification of renal tumor biomarkers, alteration of biochemical pathways resulting from loss of FLCN function, tumorigenicity of FLCN null versus FLCN restored cells, preclinical therapeutic drug testing in xenograft animal models produced from injection of these cell lines, etc. UOK 257 and UOK257-2 are thus useful cell models for studying the underlying molecular derangements associated with mTOR pathways and other biogenesis pathways in human kidney cancer and for evaluating novel therapeutic approaches for this disease. UOK257 is also one of the 40-member renal cancer cell lines in the Tumor Cell Line Repository of the Urologic Oncology Branch (UOB), National Cancer Institute (NCI).]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2111</link><pubDate>2010-07-07</pubDate></item><item><title>888-mel: A Target for Anti-Tumor Immune Responses</title><description><![CDATA[Scientists at the National Institutes of Health (NIH) have developed a human melanoma cell line designated 888-mel from the resected tumor of a 26-year old Caucasian female (patient 888) diagnosed with metastatic melanoma, a frequently terminal cancer. The 888-mel cell line was derived from three separate subcutaneous melanoma lesions on the patient and possesses many characteristics representative of melanoma cell lines developed by these researchers. Most prominently, the 888-mel cell line was used to develop a tumor infiltrating lymphocyte (TIL) culture with high affinity for the tumor cells of patient 888. When the TIL 888 culture was provided as an autologous adoptive immunotherapy treatment to patient 888 in combination with interleukin-2 (IL-2), a complete remission of subcutaneous, lung, and mucosal metastases was observed in the patient for over three years.

Since this medical breakthrough, the 888-mel cell line has been well characterized through various laboratory procedures and data involving this cell line has been published as part of numerous articles. Studies have shown that the cell line expresses a variety of tumor associated antigens (TAAs), including tyrosinase, TRP1, TRP2, gp100, MART-1, p15, gp75, mutated beta-catenin, and p53. However, 888-mel does not normally express the MAGE 1, 2, or 3 TAAs. Many melanoma cell lines are HLA-A2 restricted, but the 888-mel cell line is HLA-A2 negative. The HLA class I typing for this cell line is as follows: HLA-A0101, A2402, B55, B62, Cw5201, Cw55, DRbl*1502, DRbl*1610, DQbl*0601, DRb5*0102, DRb5*0203. 888-mel is a validated source of HLA class I peptides utilized in screens that test the reactivity of TIL cultures that are candidates for adoptive immunotherapy trials. 888-mel is also a standard cell line for studying immune responses in cancer, particularly T cell responses. Other experiments show that roscovitine, a cyclin-dependent kinase inhibitor, can induce apoptosis in the 888-mel cell line, so these cells may be useful in various cell death studies.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2115</link><pubDate>2010-07-07</pubDate></item><item><title>Identification of Cancer Stem Cells</title><description><![CDATA[Cancer stem cells (CSC) are thought to be responsible for cancer initiation, maintenance, and therapeutic failure. A hallmark of stem cells is self-renewal via asymmetric cell division (ACD) into daughter stem-cells and cells predestined for differentiation. Demonstration of fundamental stem-cell's traits such as ACD in cancers is lacking. Label retaining cells are thought to be enriched for stem-like cells. Label retaining cells are thought to be the results of either very slow cycling cells and/ or cells undergoing ACD. This invention is directed to the identification, isolation and purification of cancer stem cells by detecting asymmetrically dividing cells and/ or label retaining cells. Detection of asymmetric cell division via non-random chromosomal cosegregation (ACD-NRCC) in various human cancers defines a unique and novel class of universal cancer stem cells, and potentially suggests a novel mechanism of carcinogenesis. The isolation of CSC might be used as a basis for a potential new strategy in cancer therapeutics. The invention also might have some implications in genetics and regenerative medicine.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2127</link><pubDate>2010-07-06</pubDate></item><item><title>Human Single-domain Antibodies (dAbs) Against Insulin-like Growth Factor 1 Receptor (IGF-1R) or Its Ligands, IGF-1 and IGF-2</title><description><![CDATA[Insulin-like growth factor (IGF) mediated signaling has been implicated in the development of several epithelial cancers, such as prostate, breast, and colorectal cancers.  This technology consists of human single domain antibodies (dAbs) that bind to human insulin-like growth factor 1 receptor (IGF-1R) or its ligands, IGF-1 and IGF-2. These dAbs are comprised of only a single variable domain of an antibody with a human framework and three complementarity determining regions (CDRs). Several of these antibodies inhibit the IGF signaling pathway so they may be therapeutic candidates for the treatment of IGF-related cancers.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2128</link><pubDate>2010-07-06</pubDate></item><item><title>Diagnostic H5N1 Avian Influenza Virus Peptides</title><description><![CDATA[The recent spread of highly pathogenic H5N1 avian influenza viruses among poultry and transmission of these viruses to humans raises concerns of a potential influenza pandemic.  There is a need to track the spread of these viruses both in the animal and human populations to avert or reduce the impact of any potential influenza pandemic as well as to know the actual number (accurate surveillance) of people infected with H5N1, including individuals with subclinical H5N1 infection.

The subject technology is a specific combination of H5N1 peptides useful for assays to detect antibodies generated against a wide range of different H5N1 strains.  The combination of peptides was able to specifically detect anti-H5N1 antibodies from serum samples of H5N1 survivors at early and later times post infection while excluding antibodies generated in individuals infected with other strains of influenza virus. Also, the peptides did not react with sera from individuals vaccinated with H5N1 vaccine, in contrast to the strain-specific detection of anti-H5N1 antibodies in sera from infected individuals.  Immunoassays using the H5N1 peptide combination provide highly specific, sensitive and reproducible methods for diagnosing H5N1 infection in humans and animals.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2125</link><pubDate>2010-07-02</pubDate></item><item><title>Bacterially Expressed Influenza Virus Recombinant HA Proteins for Vaccine and Diagnostic Applications</title><description><![CDATA[Pandemic H1N1 influenza virus is a recently emergent strain of influenza virus that the World Health Organization (WHO) estimates has killed at least 14,711 people worldwide.  Avian influenza viruses are emerging health threats with pandemic potential.  Due to their global health implications, there has been a massive international effort to produce protective vaccines against these influenza virus strains.  Currently, influenza virus vaccines are produced in chicken eggs, a production method that is disadvantaged by lengthy vaccine production times and by inability to meet large-scale, global demands.

The subject technologies are specific recombinant HA proteins from H1N1, H5N1, and other strains of influenza virus produced in bacteria.  The HA proteins properly fold, form oligomers, bind fetuin, agglutinate red blood cells and induce strong neutralizing antibody titers in several in vivo animal models.  The key advantages of this technology are that expression of these proteins in bacteria reduces the vaccine production time and offers the ease of scalability for global usage, an issue with current production methods.  The recombinant HA proteins can also be used for diagnostic applications.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2126</link><pubDate>2010-07-02</pubDate></item></channel></rss>