| Multiadaptive Plan (MAP) IMRT to Accommodate Independent Movement of the Prostate and Pelvic Lymph Nodes |
Dec 2012 |
19 pages |
| Authors:
Ping Xia; CLEVELAND CLINIC FOUNDATION OH
|
 | Using our current planning margins to the prostate (6 mm posterior and 8 mm elsewhere) and pelvic lymph nodes (5 mm uniform), we found that aligning daily images to the pelvic bones would require a planning margin of the prostate greater what we used clinically. Aligning to the prostate soft tissue, a planning margin of 5 mm to the pelvic lymph nodes is adequate while the planning margin to the ... |
|
| Analysis of Sertraline in Postmortem Fluids and Tissues in 11 Aviation Accident Victims |
Nov 2012 |
18 pages |
| Authors:
Russell J Lewis; Mike K Angier; Kelly S Williamson; Robert D Johnson; FEDERAL AVIATION ADMINISTRATION OKLAHOMA CITY OK CIVIL AEROSPACE MEDICAL INST
|
| Sertraline (Zoloft R) is a selective serotonin reuptake inhibitor that is a commonly prescribed drug for the treatment of depression, as well as obsessive-compulsive disorder, panic disorder, social anxiety disorder, premenstrual dysphoric disorder, and post-traumatic stress disorder. While the use of sertraline is relatively safe, certain side effects could negatively affect a pilot's performance and become a factor in an aviation accident. The adverse side effects associated with this medication ... |
|
| Fasciotomy Reduces Compartment Pressures and Improves Recovery in a Porcine Model of Extremity Vascular Injury and Ischemia/Reperfusion |
01 Oct 2012 |
27 pages |
| Authors:
Thomas J Percival; Shimul Patel; Nickolay P Markov; Jerry R Spencer; Gabriel E Burkhardt; Lorne H Blackbourne; Todd E Rasmussen; AIR FORCE MEDICAL WING (59TH) WILFORD HALL AMBULATORY SURGICAL CENTER LACKLAND AFB TX CLINICAL RESEARCH DIV
|
| The objective of this study is to establish a model of extremity compartment syndrome following vascular injury\hemorrhage and ischemia/reprovision. An additional objective is to determine the effect of fasciotomy on measures of neuromuscular recovery. Methods: Yorkshire swine\e (75+/-5kg) underwent 35% blood volume hemorrhage, followed by 1, 3 and 6 hours of ischemia (n-17; 1HR, 3HR, 6HR) via iliac artery occlusion followed by repair and reperfusion. A second cohort (n=18) underwent ... |
|
| A Medical Center Network for Optimized Lung Cancer Biospecimen Banking |
Oct 2012 |
12 pages |
| Authors:
Christopher A Moskaluk; VIRGINIA UNIV CHARLOTTESVILLE
|
| The mission statement of the Lung Cancer Biospecimen Resource Network (LCBRN) states that the LCBRN will collect, annotate, store, and distribute human lung cancer biospecimens in a manner that embraces the highest ethical standards for human subjects research, that conforms to the best practices of biorepository science, and that furthers basic, translational and clinical research in the understanding, diagnosis and treatment of this disease . Year 2 of the award ... |
|
| Characterization of the Pathological and Biochemical Markers that Correlate to the Clinical Features of Autism |
Oct 2012 |
41 pages |
| Authors:
Abha Chauhan; F Gu; L Ji; M Barua; B Muthaiyah; M M Essa; J Wegiel; W T Brown; RESEARCH FOUNDATION FOR MENTAL HYGIENE INC STATEN ISLAND NY
|
| Brain tissue is highly heterogeneous with different functions localized in specific areas. Our results suggest that there is increased oxidative damage coupled with reduced glutathione antioxidant capacity in the selective regions of the brain in the subjects with autism. These changes in autism were specific to the frontal cortex, temporal cortex and cerebellum, while parietal and occipital cortices were not affected. Free radicals and energy (ATP) are generated by the ... |
|
| Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue |
Oct 2012 |
7 pages |
| Authors:
Farhad F Kosari; J C Cheville; G Vasmatzis; R J Karnes; M Manemann; S J Murphy; MAYO CLINIC ROCHESTER MN
|
| The goal of this project is to develop biopsy based assays to assess the probability that patients with a negative biopsy or with a prostate cancer (CaP) Gleason score 6 (GS6) biopsy actually have significant CaP of Gleason score 7 or higher which was missed during the biopsy evaluations due to insufficient sampling. Based on the concepts of the CaP field effect , this goal will be achieved by gene ... |
|
| The Role of IQGAP1 in Breast Carcinoma |
Oct 2012 |
31 pages |
| Authors:
Colin D White; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-25% of breast cancers. Increased HER2 expression is an adverse prognostic factor and correlates with decreased patient survival. HER2-positive (HER2(+)) breast cancer is treated with trastuzumab. Unfortunately, some patients are intrinsically refractory to therapy, and many who do respond initially become resistant within 1 year. Understanding the molecular mechanisms underlying HER2 signaling and trastuzumab resistance is essential to reduce breast ... |
|
| Regulation of PCNA Function by Tyrosine Phosphorylation in Prostate Cancer |
Oct 2012 |
29 pages |
| Authors:
Shao-Chun Wang; CINCINNATI UNIV OH
|
| The proliferating cell nuclear antigen (PCNA) has been widely used as a molecular marker for tumor progression and patient prognosis in a variety of human cancers. The PCNA protein has two forms: a non-functional chromatin-unbound form, and a functional chromatin-associated form. The latter form is associated with cancer and tumor progression. Currently, there are no assays which can distinguish these two, distinct forms of the PCNA protein. As a result ... |
|
| A Novel Method for Determining the Level of Viable Disseminated Prostate Cancer Cells |
Oct 2012 |
14 pages |
| Authors:
Shawn E Lupold; JOHNS HOPKINS UNIV BALTIMORE MD
|
| This project seeks to determine whether conditionally replicating adenovirus (CRAd) reporters can be exploited to detect viable and tissue-specific circulating tumor cells in the blood of patients with localized or metastatic prostate cancer. The approach specifically applies secreted reporters that are expressed under the control of the adenovirus Major Late Transcriptional Unit (MLTU) to limit reporter expression to only those cells in which the CRAd has replicated and to separate ... |
|
| Development of a Small Molecule P2X7R Antagonist as a Treatment for Acute SCI |
Oct 2012 |
70 pages |
| Authors:
Maiken Nedergaard; ROCHESTER UNIV NY
|
| This project is based on the premise that secondary damage following traumatic spinal cord can be limited by acute administration of P2X7 receptor antagonists. The objectives of the proposal were to screen P2X7 receptor antagonists in a weight drop model of spinal cord injury, define the clinical indications for administering the P2X7 receptor antagonist in various models of SCI, and obtain data for safety and toxicity data to support an ... |
|
| Evaluation of Androgen Receptor Function in Prostate Cancer Prognosis and Therapeutic Stratification |
Oct 2012 |
15 pages |
| Authors:
Albert Dobi; JACKSON (HENRY M) FOUNDATION BETHESDA MD
|
| Initially prostate cancer development is driven by the male hormone androgen through the androgen receptor, however, in some patients androgen receptor becomes dysfunctional at late stages of tumorigenesis. Early knowledge of the androgen receptor dysfunctions, what would make prostate tumors refractory to routine androgen ablation therapy, should help in patient stratification for other emerging therapeutic strategies. We proposed a novel approach for evaluating potential dysfunctions of the androgen receptor by ... |
|
| Role of Mitochondrial Inheritance on Prostate Cancer Outcome in African American Men |
Oct 2012 |
10 pages |
| Authors:
Martha Mims; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| We are examining the hypothesis that mitochondrial inheritance plays a significant role in aggressiveness of prostate cancer in African Americans. In the first year of the project we have identified 2,000 noncancerous tissues samples from African American men with prostate cancer and we have extracted DNA from 1,500 of them to date. We have validated a robust new DNA sequencing technique developed by our collaborator using single amplicon long-range ... |
|
| Improving attachments of remotely-deployed dorsal fin-mounted tags: tissue structure, hydrodynamics, in situ performance, and tagged-animal follow-up |
30 Sep 2012 |
20 pages |
| Authors:
Russel D Andrews; Robin W Baird; Gregory S Schorr; Rajat Mittal; Laurens E Howle; M B Hanson; NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION SEATTLE WA NORTHWEST FISHERIES SCIENCE CENTER
|
| We recently developed small satellite-linked telemetry tags that are anchored with small attachment darts to the dorsal fins of small- and medium-sized cetaceans. These Low Impact Minimally- Percutaneous External-electronics Transmitter (LIMPET) tags have opened up the potential to monitor the movements of numerous species not previously accessible because they were too large or difficult to capture safely, but too small for tags that implant deeply within the body. One goal ... |
|
| Novel Prostate Cancer Pathway Modeling using Boolean Implication |
Sep 2012 |
46 pages |
| Authors:
Debashis Sahoo; Jonathan R Pollack; James D Brooks; Joseph Lipsick; LELAND STANFORD JUNIOR UNIV CA
|
| Prostate cancer is the second most common cause of cancer deaths in men. We explore relationship between genes based on our novel approaches BooleanNet and MiDReG in prostate cancer and correlate them to patient information. Human prostate cancer is typically characterized by luminal cell expansion and the absence of basal cells. In normal prostate, tissue basal cells express Keratin 5 (KRT5) and Keratin 14 (KRT14). In the microarray datasets of ... |
|
| Cellular Consequences of Telomere Shortening in Histologically Normal Breast Tissues |
Sep 2012 |
12 pages |
| Authors:
Christopher M Heaphy; Pedram Argani; Alan K Meeker; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Three independent sets of normal breast tissues without evidence of cancer, either obtained from patients undergoing reduction mammoplasty or in women at time of autopsy, have been analyzed. The postdoctoral trainee has shown that moderate to dramatic telomere shortening occurs specifically in luminal epithelial cells, but not in myoepithelial cells, in the majority of histologically normal terminal ductal lobular units. However, the extent and degree of telomere shortening varies by ... |
|
| Collagen VI: A New Candidate Breast Cancer Marker Linked to Resistance to Platinum-Based Cancer Drugs |
Sep 2012 |
15 pages |
| Authors:
Jiyoung Park; TEXAS UNIV SOUTHWESTERN MEDICAL SCHOOL AT DALLAS
|
| We have observed a dramatic increase of adipocyte-derived matrix protein collagen VI (COL6) level during cancer progression, particularly it relates to a discrete C-terminal domain of the alpha3 subunit of COL6. I have established 2 lines of transgenic mice which overproduce C- terminal domain, called C5, of the COL6A3 (COL6A3-C5) under the control of MMTV promoter and crossed with MMTV-PyMT mice to see the C5 effects on mammary tumor progression ... |
|
| Harnessing Autopsied DIPG Tumor Tissues for Orthotopic Xenograft Model Development in the Brain Stems of SCID Mice |
Sep 2012 |
11 pages |
| Authors:
Xiao-Nan Li; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Diffuse intrinsic pontine glioma (DIPG) remains the most lethal childhood cancer. The slow progress in biological study and preclinical drug development is caused by the lack of fresh tumor tissues and clinically relevant animal models. The objective of our proposal is to determine if autopsied DIPG tissues can be used to develop orthotopic (intra-brain stem) xenograft mouse models that will replicate the biology of the original patient tumors. Through a ... |
|
| Transgenerational Radiation Epigenetics |
Sep 2012 |
7 pages |
| Authors:
Christopher J Kemp; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
| The carcinogenic effects of low dose radiation are not clear. Moreover, it is not known if exposure to low dose radiation increases cancer risk in offspring of irradiated parents. Radiation is known to damage DNA and cause mutations. Cancer arises in part through mutations in oncogenes and tumor suppressor genes. However, epigenetics is also known to play an important and perhaps central role in cancer induction. Epigenetics is here defined ... |
|
| On the Behaviour of Porcine Adipose and Skeletal Muscle Tissues under Shock Compression |
Sep 2012 |
244 pages |
| Authors:
James M Wilgeroth; CRANFIELD UNIV (UNITED KINGDOM)
|
| The response of porcine adipose and skeletal muscle tissues to shock compression has been investigated using the plate-impact technique in conjunction with manganin foil pressure gauge diagnostics. This approach has allowed for measurement of the levels of uniaxial stress imparted to both skeletal muscle and rendered adipose tissue by the shock. In addition, the lateral stress component generated within adipose tissue during shock loading has also been investigated. The techniques ... |
|
| The Auditory System of the Minke Whale (Balaenoptera Acutorostrata): A Potential Fatty Sound Reception Pathway in a Mysticete Cetacean |
Sep 2012 |
146 pages |
| Authors:
Maya Yamato; MASSACHUSETTS INST OF TECH CAMBRIDGE JOINT PROGRAM IN APPLIED OCEAN SCIENCE AND ENGINEERING
|
| Cetaceans possess highly derived auditory systems adapted for underwater hearing. Odontocetes, or toothed whales, are thought to use specialized acoustic fats for sound reception. However, sound reception pathways in baleen whales, or mysticetes, are unknown. We investigated the auditory system of the minke whale (small mysticete species) through dissections, biomedical imaging, biochemical analyses, and sound propagation models using the Finite Element Method (FEM). We discovered a large, well-formed fat body ... |
|
| Effect of Intraperitoneal Radiotelemetry Instrumentation on Voluntary Wheel Running and Surgical Recovery in Mice |
Sep 2012 |
10 pages |
| Authors:
Bryan G Helwig; Jermaine A Ward; Michael D Blaha; Lisa R Leon; ARMY RESEARCH INST OF ENVIRONMENTAL MEDICINE NATICK MA THERMAL AND MOUNTAIN MEDICINE DIVISION
|
| Radiotelemetry transmitters support tracking of physiologic variables in conscious animals, but the size of the transmitter may alter animal health and behavior. We hypothesized that the size of the device adversely affects body weight, food intake, water intake, circadian core temperature, activity, voluntary running patterns, and the health of internal organs and that these negative effects can be minimized with smaller transmitter devices. Male C57BL/6J mice (weight, 20 to 24 ... |
|
| Production and Characterization of a Novel OX40 Ligand for Clinical Use |
Aug 2012 |
12 pages |
| Authors:
Andrew D Weinberg; PROVIDENCE PORTLAND MEDICAL CENTER OR
|
| The goals of the second year/phase of the DOD funded research, PC073499, have been accomplished. We produced two human versions of the OX40 ligand:trimer:Ig protein. The two protein constructs have different human trimer domains (TRAF2 and Matrillin-4), which confer differing folding patterns within the two-dimension structure of the protein. These two fully human OX40L:Ig fusion proteins were administered to non-human primates to test for in vivo activity. The OX40L:Ig fusion ... |
|
| Prostate Cancer Pathology Resource Network |
Jul 2012 |
32 pages |
| Authors:
Bruce Trock; JOHNS HOPKINS UNIV BALTIMORE MD
|
| The Prostate Cancer Pathology Resource Network (which has since been renamed the Prostate Cancer Biorepository Network or PCBN) is a collaboration between the Johns Hopkins School of Medicine (JHU) and the New York University School of Medicine (NYU). The goal of the PCBN is to develop a biorepository with high quality, well annotated specimens that can be used by prostate cancer researchers. The specimens in the PCBN include prostatectomy tissues ... |
|
| Reactivation of Breast Cancer Micrometastases by Senescent Bone Marrow Stroma |
Jul 2012 |
23 pages |
| Authors:
Robert Wieder; UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY NEWARK
|
| We developed an in vitro injury model of stroma cultured from bone marrow samples of mice and human donors. We demonstrated that oxidative and hypoxic damage and estrogen deprivation can induce IL-6 and IL-8 export by human female, premenopausal stroma. We adapted a breast cancer cell co-culture model to determine effect of injury on stromal capacity to support dormancy and demonstrated that breast cancer cells induce inflammatory cytokine secretion by ... |
|
| Breast Cancer Diagnostics Based on Spatial Genome Organization |
Jul 2012 |
19 pages |
| Authors:
Thomas Misteli; Karen Meaburn; GENEVA FOUNDATION TACOMA WA
|
| Genomes are non-randomly organized within the cell nucleus. Importantly, individual gene loci undergo changes to their spatial position during disease, including cancer. We exploited, for the first time, these changes in spatial gene positioning as a novel tool for the detection of invasive breast cancer. Repositioning events in cancer cells are not a reflection of a global spatial genome reorganization and are instead gene-specific. Out of 20 genes we examined, ... |
|
| Lymphatic Vascular-Based Therapy for IBD |
Jul 2012 |
46 pages |
| Authors:
Jonathan Alexander; LOUISIANA STATE UNIV IN SHREVEPORT
|
| In the current funding period, we completed studies on the protective effects of adenoviral induced VEGF-D and compared this effect to VEGF-C. These findings were correlated with lymphatic and blood vessel density and support our hypothesis that lymphatic vessel induction is protective in IBD. These findings support lymphatic expansion as a controlling element of blood vessel expansion. We next examined the effects of VEGFR-2 kinase inhibitor, SU1498 and a VEGFR-2 ... |
|
| Examination of a Newly Discovered human Retrovirus, XMRV, in Breast Cancer |
Jul 2012 |
8 pages |
| Authors:
Fayth K Yoshimura; WAYNE STATE UNIV DETROIT MI
|
| The main objective of this research project is to test the hypothesis that a newly discovered retrovirus, XMRV, is involved in the development of human breast cancer. To accomplish this, we have examined XMRV infection in breast cancer tissue in comparison with normal breast tissue. Assay conditions for the detection of XMRV protein in formalin-fixed and paraffin-embedded (FF-PE) sections by immunohistochemistry (IHC) were optimized by the identification of a monoclonal ... |
|
| Non-thermal High-intensity Focused Ultrasound for Breast Cancer Therapy |
Jul 2012 |
17 pages |
| Authors:
Chang M Ma; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| Several in vitro studies have demonstrated the non-thermal ( 42 deg C) cell killing effect of HIFU, which resembles high linear energy transfer (LET) radiation cell damage that is not affected by the local biochemical environment and shows less radiation resistance. However, there have been no in vivo animal studies performed on non-thermal HIFU to demonstrate its therapeutic potential. This project aims to demonstrate the therapeutic potential of non-thermal HIFU ... |
|
| Breast Cancer Tissue Bioreactor for Direct Interrogation and Observation of Response to Antitumor Therapies |
Jul 2012 |
65 pages |
| Authors:
Lisa McCawley; VANDERBILT UNIV MEDICAL CENTER ATLANTA GA
|
| Tumor tissue is made up of tumor cells and other surrounding cell types in its microenvironment. This diseased tissue frequently exists in specialized tumor microenvironment such as being less oxygenated and more acidic than healthy tissue. These states profoundly impact anti-tumor drug efficacy. For disease diagnosis, a tumor is frequently biopsied. We believe that if we can maintain a biopsied portion of the tumor tissue in a similar tumor microenvironment, ... |
|
| Highly Specific Targeting of the TMPRSS2/ERG Fusion Gene in Prostate Cancer Using Liposomal Nanotechnology |
Jun 2012 |
11 pages |
| Authors:
Bulent Ozpolat; Michael Ittmann; M D ANDERSON CANCER CENTER HOUSTON TX
|
| The TMPRSS2/ERG fusion gene is detected in about 50% of prostate cancer (PCa) patients. It is highly specific for PCa and involved in proliferation and invasion of PCa cells. Some prostate cancers express a single mRNA type, while others express multiple isoforms of the fusion gene that arise via alternative splicing of the initial fusion transcript. The goal of the project is to target the four most common and biologically ... |
|
| Defining Genomic Changes in Triple-Negative Breast Cancer in Women of African Descent |
Jun 2012 |
12 pages |
| Authors:
Mark Pegram; Lisa L Baumbach; MIAMI UNIV FL
|
| Breast cancer (BC) is the second leading cause of cancer death among African-American (AA) women, with mortality 20% greater than that in Caucasians (Cauc). However, the basis for such disparity remains an enigma. Recent observations from our laboratory suggest the involvement of unidentified genes contributing to AA BC risk. Matched tumor and normal FFPE samples from Cauc and AA patients were obtained from the UM /Sylvester Breast Tissue Bank (UM/S ... |
|
| Defining Genomic Changes in Triple-Negative Breast Cancer in Women of African Descent |
Jun 2012 |
12 pages |
| Authors:
Lisa L Baumbach; Mark Begram; MIAMI UNIV FL
|
| Breast cancer (BC) is the second leading cause of cancer death among African-American (AA) women, with mortality 20% greater than that in Caucasians (Cauc). However, the basis for such disparity remains an enigma. Recent observations from our laboratory suggest the involvement of unidentified genes contributing to AA BC risk. Matched tumor and normal FFPE samples from Cauc and AA patients were obtained from the UM /Sylvester Breast Tissue Bank (UM/S ... |
|
| Response of Human Prostate Tissue to Hypofractionated Ionizing Radiation |
May 2012 |
23 pages |
| Authors:
Thomas C Sroka; ARIZONA UNIV TUCSON
|
| The aim of this proposal was to determine the differences in radiobiological response of human prostate tissue to conventional and hypofractionated radiotherapy. Specifically, this proposal characterized the predominant DNA damage response pathway from human prostatectomy specimens in response to a conventional or hypofractionated dose of ionizing radiation. We demonstrate that normal prostate tissue and prostate cancer can be cultured ex vivo using a dynamic culture system and used to study ... |
|
| Quantification of Protein Signatures in Archived Human Prostate Tissues Using Shotgun Proteomic Methods |
May 2012 |
9 pages |
| Authors:
Michael E Wright; IOWA UNIV IOWA CITY
|
| Biomarkers that robustly predict the metastatic potential of localized CaP are sorely needed to effectively treat localized CaP patients that pose the greatest risk of developing significant CaP. Biomarkers specific to significant CaP are also necessary if more effective drugs are going to be developed that can target and cure patients afflicted by this deadly disease. Proteins represent some of the most powerful molecular biomarkers to human disease such as ... |
|
| Analysis of Novel Prostate Cancer Biomarkers and their Predictive Utility in an Active Surveillance Protocol |
May 2012 |
20 pages |
| Authors:
Adam S Feldman; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| The Research Project supported by this DOD PCRP Physician Research Training Award investigates novel biomarkers for prostate cancer detection and prediction of disease outcome. This first year of my DOD PCRP PRTA has been very productive from both a translational laboratory and clinical research standpoint. In this first annual reporting period, we have begun to investigate our list of biologically relevant candidate prostate cancer biomarkers and have demonstrated promising results. ... |
|
| Gp140/CDCPI in the Development pf Prostate Cancer Metastasis |
May 2012 |
6 pages |
| Authors:
Beatrice Knudsen; CEDARS-SINAI MEDICAL CENTER LOS ANGELES CA
|
| The purpose of the research is to analyze the expression and function of gp140/CDCP1, a regulator of SRC kinase activity in prostate cancer. The scope of the project in year 3 is to determine expression in tissues from patients. The main results are from immunohistochemical analyses of gp140 in normal prostate epithelium, primary prostate cancer and metastatic prostate cancer. Gp140 RNA expression and protein membrane expression, but not total protein ... |
|
| Defining the Role of BTLA in Breast Cancer Immunosurveillance and Selective Targeting of the BTLA-HVEM-LIGHT Costimulatory System |
May 2012 |
45 pages |
| Authors:
William Gillanders; SAINT LOUIS UNIV MO
|
| Costimulatory (CD28, ICOS) and inhibitory (CTLA4, PD-1) molecules of the CD28 receptor family provide critical secondary signals regulating the balance between protective immunity and tissue injury. We recently cloned B- and T-lymphocyte attenuator (BTLA), the third inhibitory receptor of the CD28 family expressed on lymphocytes. Using BTLA-deficient mice and monoclonal antibodies specific for BTLA that we generated, we have studied several in vivo models of infection and autoimmunity, showing the ... |
|
| Organ-Specific Blood Signatures for Host Response to Infections |
03 Apr 2012 |
9 pages |
| Authors:
Leroy Hood; Kai Wang; Kathie-Anne Walters; Shawn Skerrett; Jeff Ranish; David Galas; Adrian Ozinsky; INSTITUTE FOR SYSTEMS BIOLOGY SEATTLE WA
|
| The overall objective for this project was to discover and validate host molecular fingerprints that classify inhaled microbial (bacterial and viral) biothreat agents affecting the lung. Aerosol infection experiments were performed in mice and primates, and host biomarkers were identified in lung tissue and peripheral blood plasma that classify the identity of the infectious agents. Through extensive experiments in mice, biomarkers were identified that distinguish between different bacterial biothreat agents, ... |
|
| Glucose-6-phosphate Reduces Calcium Accumulation in Rat Brain Endoplasmic Reticulum |
Apr 2012 |
9 pages |
| Authors:
Jeffrey T Cole; William S Kean; Harvey B Pollard; Ajay Verma; William D Watson; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
|
| Brain cells expend large amounts of energy sequestering calcium (Ca2+), while loss of Ca2+ compartmentalization leads to cell damage or death. Upon cell entry, glucose is converted to glucose-6-phosphate (G6P), a parent substrate to several metabolic major pathways, including glycolysis. In several tissues, G6P alters the ability of the endoplasmic reticulum (ER) to sequester Ca2+. This led to the hypothesis that G6P regulates Ca2+ accumulation by acting as an endogenous ... |
|
| Investigating Steroid Receptor Coactivator3 (SRC3) as a Potential Therapeutic Target for Treating Advanced Prostate Cancer |
Apr 2012 |
20 pages |
| Authors:
Jean C Tien; TEXAS A AND M UNIV COLLEGE STATION HEALTH SCIENCE CENTER
|
| Prostate cancer is a major health concern in the United State and understanding the molecular biology underlying the development of prostate cancer can help improve the disease prevention and therapeutic strategies. Steroid receptor coactivator 3 (SRC-3) is a nuclear receptor coactivator that is important for growth of endocrine tissues. SRC-3 enhances proliferation of prostate cancer cell lines in a cellautonomous manner and its expression is highly correlated with aggressiveness of ... |
|
| Heparanase Mechanisms in Brain - Metastatic Breast Cancer |
Apr 2012 |
10 pages |
| Authors:
Dario Marchetti; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Heparanase (HPSE) is a potent pro-tumorigenic, pro-angiogenic, and pro-metastatic enzyme over-expressed in brain metastatic breast cancer (BMBC). However, regulation of the heparanase gene is poorly understood. We hypothesized that heparanase represents a potential target for the development of novel therapies for BMBC, whose gene expression and modalities can be regulated by microRNA. Using miRanda and RNAhybrid, we identified microRNA-1258 (miR-1258) to directly target HPSE and suppress BMBC. We demonstrated miR-1258 ... |
|
| Use of eQTL Analysis for the Discovery of Target Genes Identified by GWAS |
Apr 2012 |
6 pages |
| Authors:
Stephen Thibodeau; MAYO CLINIC ROCHESTER MN
|
| The goals of this grant proposal are to: 1) construct a prostate tissue-specific expression quantitative trait loci (eQTL) dataset; and 2) utilize this dataset to identify candidate genes for existing prostate cancer (PC) risk-single nucleotide polymorphisms (SNPs) that can then be followed up in future studies. To accomplish this goal, we will perform a genome-wide SNP analysis (Illumina Human Omni 2.5M SNP array) and a genome-wide mRNA expression analysis (Illumina ... |
|
| Noninvasive Spatially Offset and Transmission Raman Mapping of Breast Tissue: A Multimodal Approach toward the in Vivo Assessment of Tissue Pathology |
Apr 2012 |
72 pages |
| Authors:
Matthew Schulmerich; ILLINOIS UNIV AT URBANA-CHAMPAIGN
|
| The purpose of this research project is to develop new approaches that can impact early diagnosis of breast cancer, post-biopsy analysis, lymph node examinations, and drug delivery studies. The scope of this training involves optimizing Raman instrumentation and methods for efficient illumination and collection of Raman scattered light originating from deep within breast tissue. Experiments encompass designing tissue phantoms using Intralipid, dyes/pigments, inclusions, and agarose gel to quantitatively characterize the ... |
|
| Identifying a Defective Pathway in Innate Immunity as an Immunoescape Mechanism for Breast Cancer Development |
Apr 2012 |
5 pages |
| Authors:
Glen Barber; MIAMI UNIV FL
|
| The innate immune system is critical for the early detection of invading pathogens and for initiating cellular host defense counter measures, which include the production of type I interferon (IFN). Immune dysfunction develops in patients with many cancer types and may contribute to tumor progression and failure of immunotherapy. This study will investigate the role of a newly identified IFN-mediated innate immunity pathway in immune surveillance, and the inactivation of ... |
|
| Impaired Clearance And Enhanced Pulmonary Inflammatory/Fibrotic Response To Carbon Nanotubes In Myeloperoxidase-Deficient Mice |
30 Mar 2012 |
10 pages |
| Authors:
Anna A Shvedova; Alexandr A Kapralov; Wei H Feng; Elena R Kisin; Ashley R Murray; Robert R Mercer; Claudette M St Croix; Megan A Lang; Simon C Watkins; Nagarjun V Konduru; PITTSBURGH UNIV PA
|
| Advancement of biomedical applications of carbonaceous nanomaterials is hampered by their biopersistence and proinflammatory action in vivo. Here, we used myeloperoxidase knockout B6.129X1-MPO (MPO k/o) mice and showed that oxidation and clearance of single walled carbon nanotubes (SWCNT) from the lungs of these animals after pharyngeal aspiration was markedly less effective whereas the inflammatory response was more robust than in wild-type C57Bl/6 mice. Our results provide direct evidence for the ... |
|
| Injectable Reactive Biocomposites For Bone Healing In Critical-Size Rabbit Calvarial Defects |
29 Mar 2012 |
17 pages |
| Authors:
Jerald E Dumas; Pamela B BrownBaer; Edna M Prieto; Teja Guda; Robert G Hale; Joseph C Wenke; Scott A Guelcher; ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX
|
| Craniofacial injuries can result from trauma, tumor ablation, or infection and may require multiple surgical revisions. To address the challenges associated with treating craniofacial bone defects, an ideal material should have the ability to fit complex defects (i.e. be conformable), provide temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of biologics. In this study, we evaluated the ability of injectable lysine-derived polyurethane ... |
|
| An In Silico Model of Endotoxic Shock Mediators (Briefing Charts) |
12 Mar 2012 |
30 pages |
| Authors:
Meghan K Makley; Jeff M Gearhart; Mark Lisanby; Charles E Hack; Lee Poeppelman; HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE WRIGHT-PATTERSON AFB OH
|
| Biologically-based in silico models of pathogen-host interactions are being designed in our lab to predict the time-course of pathogenic infection in humans. Macrophages respond to lipopolysaccharides (LPS), including the release of potent lipid autacoids, causing a cascade of events leading to endotoxic shock. However, animals have been shown to vary in response and susceptibility to E. coli endotoxin: guinea pig hamster mouse. To establish a sound basis for ... |
|
| Autophagy-Mediated Defense Response of Mouse Mesenchymal Stromal Cells (MSCs) to Challenge with Escherichia coli |
Mar 2012 |
23 pages |
| Authors:
N V Gorbunov; B R Garrison; M Zhai; D P McDaniel; G D Ledney; T B Elliott; J G Kiang; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
|
| Symbiotic microorganisms are spatially separated from their animal host, e.g., in the intestine and skin, in a manner enabling nutrient metabolism as well as evolutionary development of protective physiologic features in the host such as innate and adaptive immunity, immune tolerance, and function of tissue barriers . The major interface barrier between the microbiota and host tissue is constituted by epithelium reticuloendothelial tissue, and mucosa-associated lymphoid tissue (MALT) . Traumatic ... |
|
| The Role of ERK1/2 in the Progression of Anti-Androgen Resistance of MtDNA Deficient Prostate Cancer |
Mar 2012 |
30 pages |
| Authors:
Cody C Cook; ARKANSAS UNIV AT LITTLE ROCK MEDICAL CENTER
|
| Characterization of the mitochondrial genomic content of normal prostatic tissue and prostate cancer tumors have revealed that the carcinogenesis of normal prostate epithelial cells to prostate cancer generates heterogeneous tumors. Within a tumor, subpopulations of cancer cells harbor mitochondria with copy numbers of the mitochondrial genome that are reduced-to-depleted, in the presence of subpopulations of cancer cells that harbor elevated copy numbers of the mitochondrial genome. In the current report, ... |
|
| Characterization and Application of a Large Animal Model of Penetrating Ballistic Brain Injury (PBBI) |
Mar 2012 |
41 pages |
| Authors:
Charles E Wade; TEXAS UNIV HEALTH SCIENCE CENTER AT HOUSTON
|
| The Purpose of the proposal titled Characterization and Application of a Large Animal Model of Penetrating Ballistic Brain Injury (PBBI) is to develop a large animal model with military relevance. Of military casualties with moderate to severe traumatic brain injuries (TBI) 15-18% are due to penetrating mechanisms. Almost all (97%) of prospective clinical trials of TBI exclude patients with PBBI and no prospective clinical trials specifically focus on PBBI. A ... |
|
Reports by Keyword(s)
TISSUES(BIOLOGY)
