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Las Vegas, NV, United States

Nevada Cancer Institute , founded in 2002, was the official cancer institute for the state of Nevada from 2003 to 2013, located in Summerlin, Nevada. The Institute became part of the UC San Diego Health System in February, 2012. A non-profit organization, NVCI served patients throughout the greater Las Vegas area, offering full-service clinics in Summerlin, Nevada, and at University Medical Center, in the downtown medical district. The Institute’s mobile screening unit, the Hope Coach, has provided mammography services throughout the state.NVCI has served more than 17,000 patients since opening in 2005. The Institute was dedicated to providing innovative and collaborative cancer care, clinical trials and community education.The Institute closed on January 31, 2013. Wikipedia.


Le T.T.,Nevada Cancer Institute
BMC pharmacology & toxicology | Year: 2014

Tamoxifen, an agonist of estrogen receptor, is widely prescribed for the prevention and long-term treatment of breast cancer. A side effect of tamoxifen is fatty liver, which increases the risk for non-alcoholic fatty liver disease. Prevention of tamoxifen-induced fatty liver has the potential to improve the safety of long-term tamoxifen usage. Uridine, a pyrimidine nucleoside with reported protective effects against drug-induced fatty liver, was co-administered with tamoxifen in C57BL/6J mice. Liver lipid levels were evaluated with lipid visualization using coherent anti-Stokes Raman scatting (CARS) microscopy, biochemical assay measurement of triacylglyceride (TAG), and liquid chromatography coupled with mass spectrometry (LC-MS) measurement of membrane phospholipid. Blood TAG and cholesterol levels were measured. Mitochondrial respiration of primary hepatocytes in the presence of tamoxifen and/or uridine was evaluated by measuring oxygen consumption rate with an extracellular flux analyzer. Liver protein lysine acetylation profiles were evaluated with 1D and 2D Western blots. In addition, the relationship between endogenous uridine levels, fatty liver, and tamoxifen administration was evaluated in transgenic mice UPase1-/-and UPase1-TG. Uridine co-administration prevented tamoxifen-induced liver lipid droplet accumulation in mice. The most prominent effect of uridine co-administration with tamoxifen was the stimulation of liver membrane phospholipid biosynthesis. Uridine had no protective effect against tamoxifen-induced impairment to mitochondrial respiration of primary hepatocytes or liver TAG and cholesterol export. Uridine had no effect on tamoxifen-induced changes to liver protein acetylation profile. Transgenic mice UPase1-/-with increased pyrimidine salvage activity were protected against tamoxifen-induced liver lipid droplet accumulation. In contrast, UPase1-TG mice with increased pyrimidine catabolism activity had intrinsic liver lipid droplet accumulation, which was aggravated following tamoxifen administration. Uridine co-administration was effective at preventing tamoxifen-induced liver lipid droplet accumulation. The ability of uridine to prevent tamoxifen-induced fatty liver appeared to depend on the pyrimidine salvage pathway, which promotes biosynthesis of membrane phospholipid. Source


Roosild T.P.,Nevada Cancer Institute
PloS one | Year: 2010

Uridine phosphorylase (UPP) is a central enzyme in the pyrimidine salvage pathway, catalyzing the reversible phosphorolysis of uridine to uracil and ribose-1-phosphate. Human UPP activity has been a focus of cancer research due to its role in activating fluoropyrimidine nucleoside chemotherapeutic agents such as 5-fluorouracil (5-FU) and capecitabine. Additionally, specific molecular inhibitors of this enzyme have been found to raise endogenous uridine concentrations, which can produce a cytoprotective effect on normal tissues exposed to these drugs. Here we report the structure of hUPP1 bound to 5-FU at 2.3 A resolution. Analysis of this structure reveals new insights as to the conformational motions the enzyme undergoes in the course of substrate binding and catalysis. The dimeric enzyme is capable of a large hinge motion between its two domains, facilitating ligand exchange and explaining observed cooperativity between the two active sites in binding phosphate-bearing substrates. Further, a loop toward the back end of the uracil binding pocket is shown to flexibly adjust to the varying chemistry of different compounds through an "induced-fit" association mechanism that was not observed in earlier hUPP1 structures. The details surrounding these dynamic aspects of hUPP1 structure and function provide unexplored avenues to develop novel inhibitors of this protein with improved specificity and increased affinity. Given the recent emergence of new roles for uridine as a neuron protective compound in ischemia and degenerative diseases, such as Alzheimer's and Parkinson's, inhibitors of hUPP1 with greater efficacy, which are able to boost cellular uridine levels without adverse side-effects, may have a wide range of therapeutic applications. Source


Yang J.,Nevada Cancer Institute | Liao W.,State University of New York at Stony Brook | Ma Y.,State University of New York at Stony Brook
Current Opinion in Hematology | Year: 2012

Purpose of review: Stem cell gene SALL4 has been well characterized for its essential role in developmental events as well as embryonic stem cell pluripotency maintenance. Several current reports now shed new light on its functions in regulating hematopoietic cell self-renewal and differentiation. In this review we attempt to summarize SALL4 roles for normal hematopoiesis, and how the knowledge obtained can be used to develop advanced cell therapies. Recent findings: SALL4 may act as a critical controller to regulate the fate of hematopoietic cells. In normal bone marrow, SALL4 is selectively expressed in primitive hematopoietic precursors and rapidly downregulated following differentiation. Of particular interest, SALL4 isoforms are able to stimulate large scale ex-vivo expansion of hematopoietic stem/progenitor cells (HSCs/HPCs). The SALL4 expanded HSCs/HPCs retain multilineage repopulation and long-term engraftment activities, which are clinically meaningful. The stem cell self-renewal mediated by SALL4 is linked to epigenetic machinery. Summary: The emerging knowledge about how SALL4 regulates HSC behavior may be used in the near future to develop advanced cell therapies, for example, through large-scale stem cell expansion ex vivo. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Foon K.A.,Nevada Cancer Institute | Hallek M.J.,University of Cologne
Leukemia | Year: 2010

Progress in our understanding of chronic lymphocytic leukemia and its treatment has resulted in a more tailored approach to patient management, with different therapeutic regimens for different patient populations. The current standard of care has evolved from single-agent therapy with chlorambucil or cyclophosphamide, through the introduction of purine analogs to the more recent introduction of chemoimmunotherapy. Selection of appropriate initial therapy should be based primarily on patient characteristics such as age, performance status and the expected clinical course of the leukemia based on established risk factors. Achieving a complete and durable response is the major goal for fit patients; chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab would be advantageous. Alternatively, in unfit patients, controlling symptoms is the essential treatment goal and a regimen with a more favorable toxicity profile should be applied. This manuscript reviews the data that has lead to current treatment choices, advises on tailored therapies and discusses emerging trends. Data for this review was identified by a search of electronic information including Medline and PubMed databases, conference proceedings and trial registers. Critical analysis of extracted data was undertaken with attention to trial phase, treatment schedules and end points, including response rates, follow-up times, progression-free survival and overall survival. © 2010 Macmillan Publishers Limited All rights reserved. Source


Patent
Nevada Cancer Institute | Date: 2012-05-15

The present invention relates to the compositions, formulations and methods of treating fatty liver disorders, such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) and their sequelae by administration of uridine or a compound that modulates one or more uridine phosphorylases in a subject in need thereof.

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