| Traumatic Brain Injury: Care and Treatment of Operation Enduring Freedom and Operation Iraqi Freedom Veterans |
25-Nov-2009 |
|
| Authors:
Amalia K Corby-Edwards; LIBRARY OF CONGRESS WASHINGTON DC CONGRESSIONAL RESEARCH SERVICE
|
 | Traumatic brain injury (TBI), defined in the medical literature as a disruption in brain function that is caused by a head injury, has become known as one of the signature wounds of the wars in Iraq and Afghanistan due to its high occurrence in post-deployment service members and veterans of these wars. As service members return home, many need ongoing care for mild, moderate, or severe TBI. The growing number ... |
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| Alaska Native Parkinson's Disease Registry |
Nov-2009 |
10 pages |
| Authors:
Brian A Trimble; ALASKA NATIVE TRIBAL HEALTH CONSORTIUM ANCHORAGE AK
|
 | Parkinsonism (PS) is a syndrome characterized by tremor, rigidity, slowness of movement, and problems with walking and balance. Parkinson's disease is the most common form of PS, accounting for about 1% of the U.S. population over age 50 years. Little information is available about trends in PS, particularly among Alaska Natives. This registry initiates a program of epidemiological assessment of PS among Alaska native people to study the natural history ... |
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| A Systematic Approach to Alternative Medical Procedures |
Oct-2009 |
3 pages |
| Authors:
Ronald N Kostoff; MITRE CORP MCLEAN VA
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| In 2007, medical costs in the United States were estimated at $2.4 trillion (Keehan et al. 2008). If one included the costs of time lost as a result of illness and of insuring those now uninsured or underinsured, the total would be closer to $3 trillion. Most of the non-time-lost costs are incurred for diagnostics, treatments, drugs, and other therapies. There are ways to lower the costs of health care, ... |
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| To Stay a Soldier |
Oct-2009 |
11 pages |
| Authors:
Chuck Callahan; ARMY WAR COLL CARLISLE BARRACKS PA
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| Doc, if you try to take me out of the 82d, you'll be hearing from my congressman. The young soldier with tattooed arms strained against the bedrails, his eyes searching the doctor's face above, his twisted, purplish leg surrounded by a black steel cage of bolts and rods that held his shattered bones together. He was one of many men and women wheeled from surgery to therapy to their rooms ... |
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| Noninvasive Imaging of Heterotopic Ossification and Targeted Intervention |
Sep-2009 |
14 pages |
| Authors:
Shi Ke; BAYLOR COLL OF MEDICINE HOUSTON TX
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| Heterotopic bone can form in muscle or other soft tissue that is adjacent to a fracture, blast wound, or amputation injury. This condition causes severe pain and disability. Chemokine-directed stem cell homing is an important early stage of heterotopic bone formation. CXCR4 is the most important chemokine in this procedure. Noninvasive evaluation of CXCR4 status is important for early diagnosis and treatment. We have synthesized peptide-based CXCR4 imaging agents and ... |
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| Mission Connect Mild TBI Translational Research Consortium |
Aug-2009 |
18 pages |
| Authors:
Thomas A Kent; James Tour; BAYLOR COLL OF MEDICINE HOUSTON TX
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| This project addresses the treatment of deleterious oxy-radical production following traumatic brain injury using anti-oxidant nanomaterials. Our evidence indicates that traumatic brain injury generates superoxide radical rapidly and persistently, which is exacerbated by systemic hypotension and resuscitation. Conventional anti-oxidant therapy is either not sufficiently potent nor long lasting. Nanomaterials synthesized in our collaborators in the Tour laboratory demonstrated potent anti-oxidant activity in preliminary results. We have developed several assays in ... |
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| Mission Connect Mild TBI Translational Research Consortium |
Aug-2009 |
16 pages |
| Authors:
J R Perez-Polo; TEXAS UNIV MEDICAL BRANCH AT GALVESTON
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| Brain injury, particularly mild 'blast type' injuries due to improvised exploding devices are difficult to detect clinically, although there are long term cognitive and behavioral deficits. Key inflammatory cytokines are unregulated after traumatic insults that play a role in the development of long-term deficits. Early events are increased IL-1 and TNFalpha cytokine levels, that contribute to cell death and inflammation, and microglial and astrocytic activation, mediators dysfunction via persistent inflammation. ... |
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| The Role of eIF4E Activity in Breast Cancer |
Aug-2009 |
12 pages |
| Authors:
Thomas A Hughes; L A Coleman; S Satheesha; LEEDS UNIV (UNITED KINGDOM)
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| Increased eIF4E expression occurs in many breast cancers and makes fundamental contributions to carcinogenesis by stimulating expression of cancer-related genes at post-transcriptional levels. This key role is highlighted by the facts that eIF4E levels can predict prognosis and that eIF4E is an established therapeutic target. However, eIF4E activity is a complex function of expression levels and phosphorylation statuses of eIF4E and its regulatory proteins. Our hypothesis was that combined analyses ... |
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| Exercise to Counteract Loss of Bone and Muscle During Androgen Deprivation Therapy in Men with Prostate Cancer |
Aug-2009 |
13 pages |
| Authors:
Wendy M Kohrt; L M Glode; Robert S Schwartz; Daniel W Barry; COLORADO UNIV AURORA CO
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| The original objective was to determine whether a 1-year intensive resistance exercise training (RT) program is more effective than a moderate-intensity walking program in ameliorating the effects on body composition of androgen deprivation therapy (ADT) in men with prostate cancer. It was postulated that: 1) RT will attenuate the declines in bone mineral density (BMD) and fat-free mass (FFM) to a greater extent than walking; and 2) both RT and ... |
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| Evaluating Surgical Margins with Optical Spectroscopy and Spectral Imaging Following Breast Cancer Resection |
Aug-2009 |
61 pages |
| Authors:
Matthew D Keller; VANDERBILT UNIV NASHVILLE TN
|
| In one aspect of the fellowship, a training program has been established to expose the PI to a wide range of current breast cancer research, particularly through seminars in imaging and cancer biology fields. Collaborations with other graduate students and mentoring of undergraduate students has also been pursued. In the research portion, polarized fluorescence and reflectance-based imaging was initially pursued to examine breast tumor surgical margin status intraoperatively during breast ... |
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| A Large-Scale Quantitative Proteomic Approach To Identifying Sulfur Mustard-Induced Protein Phosphorylation Cascades |
31-Jul-2009 |
7 pages |
| Authors:
Patrick A Everley; Dillman; James F III; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD RESEARCH DIVISION
|
| Sulfur mustard [SM, bis-(2-chloroethyl) sulfide] is a potent alkylating agent and chemical weapon. While there are no effective treatments for SM-induced injury, current research focuses on understanding the molecular changes upon SM exposure. Indeed, efforts that seek a more comprehensive analysis of proteins and post-translational modifications are critical for understanding SM-induced toxicity on a more global scale. Furthermore, these studies can uncover proteins previously uncharacterized in SM-exposed cells, which in ... |
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| Adoptive Immunotherapy Combined with Hematopoietic Cell Transplantation as a Therapeutic Treatment of Prostate Cancer |
Jul-2009 |
19 pages |
| Authors:
Beatrice Knudsen; Scott S Graves; Rainer Storb; Bradley Stone; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
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| We determined that a prostate cell lysate prepared from canine prostate tissue was immunogenic when injected in female dogs. In addition to the known prostate antigen, canine prostate specific esterase (CPSE), we identified by molecular weight several other proteins against which the dog made IgG antibodies. Using a mixed lymphocyte reaction, we found that a cellular response was generated against the prostate cell lysate after the female dog was injected ... |
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| Humanized Androgen Receptor Mice: A Genetic Model for Differential Response to Prostate Cancer Therapy |
Jul-2009 |
12 pages |
| Authors:
Diane M Robins; MICHIGAN UNIV ANN ARBOR
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| In mice in which human androgen receptor (AR) replaces the endogenous murine gene, variation in the length of a polymorphic N-terminal polyglutamine tract affects initiation, progression and therapy response prostate tumors. This provides a genetic paradigm in which to dissect AR functions that determine response to therapy. We are studying the role of the AR Q tract in ligand-independent AR activation in vitro and in a mouse model with prostate ... |
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| Role of XIAP in Therapeutic Resistance in Inflammatory Breast Cancer |
Jul-2009 |
49 pages |
| Authors:
Katherine M Aird; DUKE UNIV DURHAM NC
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| Inflammatory breast cancer (IBC) is a highly aggressive form of locally advanced breast cancer that is often characterized by ErbB2 and ErbB1 overexpression. ErbB-targeting is clinically relevant using trastuzumab, an anti-ErbB2 antibody, and lapatinib, a small molecule ErbB1/2 kinase inhibitor. However, acquired resistance is common even in those patients who show an initial clinical response; this resistance is in part due to apoptotic dysregulation, which allows transformed cells to survive ... |
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| Altered MicroRNA Activity Promotes Resistance to Endocrine Therapy |
Jul-2009 |
42 pages |
| Authors:
Diana M Cittelly; COLORADO UNIV AURORA CO
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| MicroRNAs (miRNAs) have tumor suppressive and oncogenic potential in human cancer, but little is known about the extent at which miRNA expression is modified after anti-estrogen treatment and the contribution of specific miRNAs to the acquisition of anti-estrogen resistance. To answer this question, in Aim 1, we performed miRNA profiling of tamoxifen-resistant and sensitive breast cancer cells treated with Estradiol or Tam. Several miRNAs were intrinsically downregulated in tam-resistant cells ... |
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| Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B Cell Autoreactivity |
Jul-2009 |
16 pages |
| Authors:
Betty Diamond; FEINSTEIN INST FOR MEDICAL RESEARCH MANHASSET NY
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| Systemic lupus erythematosus (SLE) is an autoimmune disease that occurs preferentially in women. In murine models of SLE, it is clear that increased or sustained high physiologic levels of estradiol can accelerate onset of disease and exacerbate disease severity. We have shown that estradiol alters B cell maturation in vivo but does so in a genetically restricted fashion. We have also shown that estradiol can act directly on B cells ... |
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| The Role of Autophagy with Arginine Deiminase as a Novel Prostate Cancer Therapy |
Jul-2009 |
31 pages |
| Authors:
Randle Kim; CALIFORNIA UNIV DAVIS
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| Arginine deprivation by arginine deiminase (ADI) is a novel therapy that is effective against prostate cancers that lack argininosuccinate synthetase (ASS), the rate-limiting enzyme for de novo arginine synthesis. We show that in ASS negative CWR22Rv1 prostate cancer cells, ADI rapidly induced autophagy through AMPK/mTOR/S6K as well as ERK1/2 pathways in order to delay the onset of caspase-independent apoptosis. Inhibiting autophagy with chloroquine or Beclin1 siRNA accelerated and enhanced ADI-induced ... |
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| Identification of the Mechanisms Underlying Antiestrogen Resistance: Breast Cancer Research Partnership between FIU-UM Braman Family Breast Cancer Institute |
Jun-2009 |
13 pages |
| Authors:
Deodutta Roy; FLORIDA INTERNATIONAL UNIV MIAMI
|
| This research proposal has two primary objectives which are to (1) increase FIU investigators' research expertise and competitive ability to succeed as independent breast cancer researchers; and (2) to execute research with the promise of identifying molecular causes of breast tumor resistance to anti-estrogen therapy. This research is of significant merit because of its clinical relevance to breast cancer. Secondly, the research accomplishments through the FIU/BFBCI training program will lead ... |
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| Regulation and Action of SKP2 in Cell and Tumor Models: Mechanisms Underlying Aggressive Growth in Basel-Like Breast Cancer |
Jun-2009 |
6 pages |
| Authors:
Katerina Fagan-Solis; MASSACHUSETTS UNIV AMHERST
|
| The objective of this research is to further our understanding of the molecular mechanisms underlying the aggressive growth of estrogen receptor (ER)-negative, basal-like breast tumors. My goal is to determine if SKP2 is a viable new therapeutic target to specifically treat patients who have tumors that are independent of ER signaling. The most significant finding during this research period is that SKP2 protein was expressed in 60% (21 of 35) ... |
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| Advances in Breast Cancer Therapy |
Jun-2009 |
10 pages |
| Authors:
Holly Gallion; PRECISION THERAPEUTICS INC PITTSBURGH PA
|
| PTI has received WIRB approval and the University of Pittsburgh IRB approval for this study. PTI has engaged 19 research sites in this research and four contracts have been successfully negotiated and executed. Another six research sites are determining clinical and budgetary feasibility. Pending the approval of the DoD and the WIRB of this first set of research sites submitted for approval, it is anticipated we will have the first ... |
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| Mechanistic Basis of Calmodulin Mediated Estrogen Receptor Alpha Activation and Antiestrogen Resistance |
Jun-2009 |
42 pages |
| Authors:
Jeffrey L Urbauer; Ramona J Bieber-Urbauer; Carrie E Jolly; GEORGIA UNIV RESEARCH FOUNDATION INC ATHENS
|
| Estrogen receptor alpha (ERalpha) is the principle chemotherapeutic target for estrogen dependent breast cancers. Calmodulin (CaM) is an obligatory ERalpha activator. Moreover, antiestrogens (tamoxifen) bind tightly to CaM, and some therapeutic benefits of antiestrogens for breast cancers are hypothesized to derive from this interaction. The purpose and scope of the research is to define the structural requisites of ERalpha activation by CaM and the relationship between tamoxifen binding to CaM, ... |
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| The Modulation of Fibrosis in Scleroderma by 3-deoxyglucosone |
Jun-2009 |
27 pages |
| Authors:
Carol M Artlett; DREXEL UNIV PHILADELPHIA PA
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| Scleroderma is a disease where excess collagen is deposited in the skin and internal organs. The tissues become hard and in the end fail to function. To date there is no cure, nor, is there an effective therapy that will control the deposition of the collagen. The goals of this application were to investigate the cellular signaling within fibroblasts that were mediated by the glycation end product, 3DG. We find ... |
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| Targeting Signal Transducers and Activators of Transcription-3 (STAT3) as a Novel Strategy in Sensitizing Breast Cancer to EGFR-Targeted Therapy |
Jun-2009 |
10 pages |
| Authors:
Hui-Wen Lo; DUKE UNIV DURHAM NC
|
| Our research effort in the past award year has resulted in several interesting findings that support the study hypothesis: deregulated EGFR and STAT3 pathways synergistically contribute to the malignant biology of breast cancer and that combined uses of anti-EGFR and anti- STAT3 treatments result in significantly increased breast cancer cell death compared to single agent treatments. First, we have created isogenic breast cancer cell lines to stably express modestly activated ... |
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| Pharmacological Studies of NOP Receptor Agonists as Novel Analgesics |
May-2009 |
36 pages |
| Authors:
Mei-Chuan Ko; MICHIGAN UNIV ANN ARBOR
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| The studies proposed in this project will test the hypotheses that in the non-human primate (1) the functions and behavioral effects of the NOP receptor are independent of classical opioid receptors, (2) activation of the NOP receptor produces strong antinociception without abuse liability, and (3) NOP receptor agonists possess a promising therapeutic profile as analgesics compared to mu opioids following repeated administration in primates. Several key findings have been obtained ... |
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| Inhibition of Ovarian Cancer by microRNA-mediated Regulation of Telomerase |
May-2009 |
51 pages |
| Authors:
Brittney-Shea Herbert; INDIANA UNIV INDIANAPOLIS
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| A hallmark of ovarian cancer is its limitless proliferative potential which is governed in part by elevated levels of human telomerase (hTERT) or telomerase activity. However, how telomerase can be regulated in normal cells, and how this regulation can be lost during cancer progression, is not completely understood. microRNAs (miRNAs) are evolutionarily conserved, small, non-coding, single-stranded, 19-23 nucleotide RNA molecules that are estimated to negatively regulate protein encoding genes including ... |
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| A Blast Model of Traumatic Brain Injury in Swine |
May-2009 |
7 pages |
| Authors:
Samuel S Panter; NORTHERN CALIFORNIA INST FOR RESEARCH AND EDUCATION SAN FRANCISCO
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| Although blast-induced traumatic brain injury (BI-TBI) is a significant cause of morbidity and behavioral dysfunction in warfighters returning from Iraq, laboratory models are not currently available to study the mechanisms underlying this critical injury and develop new therapies to treat survivors. Many TBI models are performed in rodents, and data from these models have been used as a basis for several disappointing Phase III clinical trials in humans with TBI. ... |
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| Efficacy of Intranasal Scopolamine Gel for Motion Sickness Treatment in Aviation Candidates |
13-Apr-2009 |
43 pages |
| Authors:
Rita G Simmons; Jeffrey B Phillips; Renee A Lojewski; NAVAL AEROSPACE MEDICAL RESEARCH LAB PENSACOLA FL
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| Results from preliminary studies indicate that intranasal scopolamine (INSCOP) has faster absorption, higher bioavailability and reliable therapeutic index than oral or transdermal forms. The objective of this study was to determine the efficacy of INSCOP for the treatment of motion-induced sickness and to estimate the rate of absorption. After completing baseline physiolgical, biological and cognitive assessments, 16 aviation candidates were given 0.4 mg of INSCOP and a placebo and were ... |
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| Multidisciplinary Biomarkers of Early Mammary Carcinogenesis |
01-Apr-2009 |
7 pages |
| Authors:
Julie Ostrander; DUKE UNIV DURHAM NC
|
| The purpose of the proposed research is to develop novel optical technologies to identify high-risk premalignant changes in the breast. Our proposed research will first test specific optical parameters in breast cancer cell lines and models of early mammary carcinogenesis, and then develop methods to test the optical parameters in random periareolar fine needle aspirate (RPFNA) samples from women at high-risk for developing breast cancer. Over the last year, we ... |
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| Angiogenesis Research to Improve Therapies for Vascular Leak Syndromes, Intra-Abdominal Adhesions, and Arterial Injuries |
Apr-2009 |
176 pages |
| Authors:
Donald Ingber; CHILDREN'S HOSPITAL CORP BOSTON MA
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| The three goals of this project are: (i) to discover and develop novel drugs which could prevent or reverse the vascular leak syndrome; (ii) to develop angiogenesis inhibitors which would inhibit post-operative abdominal adhesions; and, (iii) to isolate endothelial progenitor cells from blood, capable of being expanded in vitro and applied to vascular grafts. Progress has been made in each category: we have made considerable progress in determining the efficacy ... |
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| New Approaches for Prostate Cancer Combination Therapy |
Apr-2009 |
34 pages |
| Authors:
Luiz F Zerbini; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| The mechanisms underlying the antineoplastic actions of NSAIDs remain poorly understood. We started deciphering now the mechanisms by which NSAIDs induce programmed cell death and growth arrest in cancer. In this report we show that induction of the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (MDA-7/IL-24) and the expression of growth arrest and DNA damage inducible (GADD) 45 alpha and gamma by several NSAIDs is an essential step for G2/M growth ... |
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| Development and Screening of Subtractive RNAi Libraries from Ovarian Cancer Cell Lines |
Apr-2009 |
6 pages |
| Authors:
Alexandre B Dimtchev; GEORGETOWN UNIV WASHINGTON DC
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| The Specific aims of this proposal are: (1) Construction of two subtractive RNAi libraries targeting mRNA transcripts predominantly present in an (a) advanced ovarian cancer cell line and (b) metastatic ovarian cancer cell line. (2) Screen for genes vitally important for survival and growth. The two malignant cell lines will be transfected with individual clones from the subtractive RNAi libraries and the effect on viability will be monitored. Clones from ... |
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| Center of Excellence for Individualization of Therapy for Breast Cancer |
Apr-2009 |
43 pages |
| Authors:
George W Sledge; INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
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| We have been waiting for the group to accumulate at least 20 serum samples from each of the patient sets we decided would benefit from a proteomic analysis. We revised this approach during the March meeting, since the collection process has been going very slowly. During the meeting, we decided to begin a somewhat different series of analyses, in which we would look at the baseline proteomic signatures for all ... |
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| Development of a Multifaceted Ovarian Cancer Therapeutic and Imaging Agent |
Apr-2009 |
7 pages |
| Authors:
Francis S Markland; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
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| Ovarian cancer (OC) is the deadliest of all gynecological cancers, with five year survival rates of 45%. One critical feature of the disease is that two-thirds of the women diagnosed have advanced disease, and the five year survival rate of this group is 30%. This project outlines the development of a recombinant version of a member of a class of proteins known as disintegrins as an innovative imaging and diagnostic ... |
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| CD24 as a Potential Therapeutic Target in Prostate Cancer |
Apr-2009 |
28 pages |
| Authors:
Pan Zheng; MICHIGAN UNIV ANN ARBOR
|
| This is the first annual report on the grant CD24 as a Potential Therapeutic Target in Prostate Cancer. CD24 (heat-stable antigen) is a cell surface GPI-anchored mucin-like glycoprotein with broad expression on a variety of cell types, including hematopoietic cells, neuronal cells and various epithelial cells. There are accumulating evidence showing CD24 plays an important role in tumor development and tumor metastasis. We hypothesized that the expression of CD24 on ... |
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| Characterizing the Role of 1p36 Deletion in Breast Cancer and Identifying Candidate Tumor Suppressors |
Apr-2009 |
10 pages |
| Authors:
Christoper S Hackett; CALIFORNIA UNIV SAN FRANCISCO
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| Over 60% of human breast tumors display a deletion of one copy of the 1p36 region of the short arm of chromosome 1. Patients whose tumors carry this deletion show a three-fold increase in mortality, suggesting a biological role for this deletion in tumor development, and suggesting the presence of one or more tumor suppressors in this region. Purpose: Characterization of the unique biology of tumors with 1p36 deletion, and ... |
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| Breast Tumor Detection and Treatment Using Tarvacin Labeled with Arsenic Radionuclides |
Apr-2009 |
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| Authors:
Ralph P Mason; TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER
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| We will generate a novel approach for detection and therapy of advanced disseminated breast cancer based on three fundamentally novel discoveries and concepts. The first critical component exploits the discovery of a novel antibody, which targets phosphatidylserine (PS), expressed on tumor vasculature and stimulates recruitment of host defense cells to attack the vasculature. In collaboration with Peregrine Pharmaceuticals, this agent has been chimerized and is being developed for clinical trials ... |
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| New Advances in Molecular Therapy for Muscle Repair after Diseases and Injuries |
Apr-2009 |
136 pages |
| Authors:
Bing Wang; Xiao Xiao; Johnny Huard; Yong Li; Bruno Peault; Bridget Deasy; Paula Clemens; CHILDREN'S HOSPITAL OF PITTSBURGH PA
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| Muscle injuries, especially pulls and strains, are among the most common and most frequently disabling injuries sustained by athletes and soldiers. Although injured muscles heal naturally, the regeneration is very slow and often yields incomplete functional recovery. In injured muscle, regeneration begins shortly after injury, but the healing process is rather inefficient and is hindered by fibrosis-that is, scar tissue formation. More importantly, the scar tissue that often replaces damaged ... |
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| SXR, A Novel Target for Breast Cancer Therapeutics |
Apr-2009 |
31 pages |
| Authors:
Suman Verma; CALIFORNIA UNIV IRVINE
|
| Many structurally and functionally distinct SXR activators inhibited the proliferation of MCF-7 and ZR-75-1 breast cancer cells by inducing cell cycle arrest at the G1/S phase followed by apoptosis. Decreased growth in response to SXR activation was associated with stabilization of p53 and up-regulation of cell cycle regulatory and pro-apoptotic genes such as p21, PUMA and BAX. These gene expression changes were preceded by an increase in inducible nitric oxide ... |
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| Physiologic and Endocrine Correlates of Overweightness in African Americans and Caucasians |
27-Mar-2009 |
94 pages |
| Authors:
Merrily Poth; Tracey Sbrocco; Patricia A Deuster; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF MILITARY AND EMERGENCY MEDICINE
|
| Obesity has reached epidemic levels and the incidence continues to rise. The current study was seeking to examine the hypothesis that obesity may reflect dysfunctioning of the hypothalamic-pituitary-adrenal (HPA) axis in response to stressors. African American persons are at greatest risk, but reasons for this difference are unknown. We studied 126 healthy men and women of Caucasian (CA) and African American (AA) ethnicity and examined their responses to physiologic stressors: ... |
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| Multidisciplinary Analysis of Cyclophilin a Function in Human Breast Cancer |
Mar-2009 |
48 pages |
| Authors:
Jiamao Zheng; NORTHWESTERN UNIV CHICAGO IL
|
| The major goal of the proposed project is to understand how cyclophilin A (CypA) modulates the prolactin (PRL) receptor (PRLr)-associated signaling and to determine the effects of altered CypA levels and activity on PRL signaling and breast cancer phenotype by combining biophysical structural investigations with studies in cell and animal models. The knowledge we obtained from this study will contribute to a greater understanding of the mechanism of PRL action. ... |
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| Ets2 Contributions of the Tumor Microenvironment in Breast Cancer Metastasis |
Mar-2009 |
31 pages |
| Authors:
Jillian L Werbeck; OHIO STATE UNIV RESEARCH FOUNDATION COLUMBUS
|
| According to the American Cancer Society, the chance being diagnosed with invasive breast cancer is about 1 in 8 and the chance of dying from breast cancer is about 1 in 33. The recent trend toward a decrease in breast cancer mortality rate is largely due to increased diagnosis of early stage disease, while therapeutic options for advanced stage breast carcinomas are still fairly limited. Currently, metastasis is the most ... |
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| Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy |
Mar-2009 |
18 pages |
| Authors:
Peter S Nelson; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
| The Purpose of this proposal is to exploit a molecular correlate of the Gleason grading system for prostate carcinoma in order to: a) develop improved outcome predictors; and b) identify therapeutic strategies. During this project period we have evaluated in excess of 25 prostate cancer antigens by Western blot and tissue-based assays and identified 3 with detectable levels in the plasma. We also determined that developmental genes involved with invasive ... |
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| Mammary Gland Tumor Development in Transgenic Mice Overexpressing Different Isoforms of the CDP/Cux Transcription Factor |
Mar-2009 |
25 pages |
| Authors:
Chantal Cadieux; LADY DAVID INST MONTREAL (QUEBEC)
|
| Short CUX1 isoforms were found to be overexpressed in breast cancer cell lines, in human breast tumors and in uterine leiomyomas, suggesting that these proteins play a key role in tumor development and progression. My project consisted in analyzing the effect of these CUX1 isoforms on mammary gland development and tumorigenesis. Also, I worked on the identification of targets of CUX1 mediating its oncogenic properties. So far, I have shown ... |
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| Exploiting the Immunological Effects of Standard Treatments in Prostate Cancer |
Mar-2009 |
40 pages |
| Authors:
Brad H Nelson; BRITISH COLUMBIA CANCER AGENCY VANCOUVER
|
| We previously demonstrated that hormone therapy (HT) and radiation therapy (RT) induce tumor-specific autoantibody responses in human prostate cancer, and this grant investigates the clinical significance of these findings. In Aim 1, the findings that HT induces autoantibody and T cell responses against PABPN1 in the Shionogi tumor model and that these immune responses are associated with inferior outcomes have recently been submitted for publication. We have also shown that ... |
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| Pharmacological Prevention and Reversion of Erectile Dysfunction After Radical Prostatectomy, by Modulation of Nitric Oxide/cGMP Pathways |
Mar-2009 |
65 pages |
| Authors:
Nestor F Gonzalez-Cadavid; CHARLES DREW UNIV LOS ANGELES CA
|
| During Year 2 an experimental article previously submitted was completed and extensively revised for its ulterior recent publication (P-1), describing the time course of histological and functional changes affecting the penile corpora cavernosa after bilateral cavernosal nerve resection (BCNR) in the rat, as an experimental model for erectile dysfunction subsequent to radical prostatectomy for prostate cancer. This condition seriously affects the quality of life of a large fraction of male ... |
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| The Role of Backup NHEJ Repair in Creating Genomic Instability in CML. Addendum |
Mar-2009 |
18 pages |
| Authors:
Feyruz Rassool; MARYLAND UNIV BALTIMORE SCHOOL OF MEDICINE
|
| The BCR-ABL1 fusion gene in Philadelphia (Ph)-+ve chronic myeloid leukemis (CML) encodes a constitutively active tyrosine kinase that causes uncontrolled cellular proliferation. BCR-ABL1 expression results in elevated levels of reactive oxygen species (ROS), an increased incidence of DNA double strand breaks (DSBs), error-prone repair and genomic instability. We recently demonstrated that an error-prone alternative (alt) NHEJ pathway involving DNA ligase IIIa/XRCC1 is upregulated in CML cells. Knockdown of alt NHEJ ... |
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| The BESCT Lung Cancer Program (Biology, Education, Screening, Chemoprevention, and Treatment) |
Mar-2009 |
27 pages |
| Authors:
Waun K Hong; Fadlo R Khuri; M D ANDERSON CANCER CENTER HOUSTON TX
|
| BESCT program aims to define molecular abnormalities contributing to lung cancer initiation and progression and to develop innovative therapeutic approaches for this cancer. Our specific aims are 1) to understand molecular alterations in lung cancer, 2) to develop chemoprevention strategies for lung cancer, and 3) to implement experimental molecular therapeutic approaches for lung cancer treatment. |
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| The Cadherin Interaction as a Rate Limiting Step in Breast Cancer Metastasis to the Liver |
Mar-2009 |
13 pages |
| Authors:
Yvonne Chao; PITTSBURGH UNIV PA
|
| Our overall objective is to identify molecular elements that enable breast cancer cells to establish metastases. Finding targeted approaches to inhibit rate-limiting events of metastatic growth is preferable to using therapeutics that are cytotoxic on a systemic level. Cadherins make up a family of adhesion molecules that mediate Ca2+-dependent cell-cell adhesion at points of cell-cell adhesion (Goodwin and Yap, 2004). Epithelial-cadherin (E-cadherin), the prototype classical cadherin present on the surface ... |
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| Ethyl Pyruvate Provides Therapeutic Benefits to Resuscitation Fluids |
Feb-2009 |
16 pages |
| Authors:
Luis Ulloa; UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY NEWARK
|
| Many promising strategies in experimental models of hemorrhage have failed in clinical trials, in part because classical experimental models may not mimic clinical settings. Unlike classical experimental models, hemorrhage in critical care is normally associated with collateral trauma that affects the physiological responses during resuscitation. Unlike rodents, swine are an optimal species donor for experimental hemorrhage as they have an anatomy, physiology and hemodynamic responses that closely resembles human. Here, ... |
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| Biological Effects of TMPRSS2/ERG Fusion Isoforms in Human Prostate Cancer |
Feb-2009 |
17 pages |
| Authors:
Jianghua Wang; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| It has been established that 15-80% of prostate cancers harbor the TMPRSS2/ERG fusion gene depending on the clinical stage, with 40-60% of surgically treated cancers containing the gene fusion. Thus it is the single most common molecular alteration in prostate cancer and as such is a critical target for diagnostic testing and novel therapies. However, there is currently very little information about the biological functions of TMPRSS2/ERG fusions and the ... |
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