| Human Neural Cell-Based Biosensor |
07 Dec 2012 |
4 pages |
| Authors:
Steven L Stice; ARUNA BIOMEDICAL INC ATHENS GA
|
 | Our goal is to provide a more biologically relevant model of human physiology for the purpose of developing in vitro, cell based biosensors for environmental toxins. Specifically we plan to develop human neural based biosensors by using ArunA's neural cell lines derived from both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). This report describes the progress made in these major areas: (1) directed differentiation of ... |
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| Ebola Virus Genome Plasticity as a Marker of Its Passaging History: A Comparison of In Vitro Passaging to Non-Human Primate Infection |
28 Nov 2012 |
8 pages |
| Authors:
Jeffrey R Kugelman; Michael S Lee; Cynthia A Rossi; Sarah E McCarthy; Sheli R Radoshitzky; John M Dye; Lisa E Hensley; Anna Honko; Jens H Kuhn; Peter B Jahrling; Travis K Warren; Chris A Whitehouse; Sina Bavari; Gustavo Palacios; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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| To identify polymorphic sites that could be used as biomarkers of Ebola virus passage history, we repeatedly amplified Ebola virus (Kikwit variant) in vitro and in vivo and performed deep sequencing analysis of the complete genomes of the viral subpopulations. We then determined the sites undergoing selection during passage in Vero E6 cells. Four locations within the Ebola virus Kikwit genome were identified that together segregate cell culture-passaged virus and ... |
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| Nanobioinformatics: Emerging Computational Tools to Understand Nano-Bio Interaction |
16 Nov 2012 |
7 pages |
| Authors:
U S Murty; INDIAN INST OF CHEMICAL TECHNOLOGY HYDERABAD
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| Nanoparticles (NP) are being used in our daily life; these help humans in many ways; usage of these NP's have increased tremendously recently without knowing their complications or health problems they could lead to; these nanoparticles should be studied for their toxicities, because the nano-size properties of every element are found to vary from the element in micro size, and many nanoparticles were found to be highly reactive in their ... |
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| Adoptive Immunotherapy for Epithelial Ovarian Cancer Using T Cells Simultaneously Targeted to Tumor and Tumor-Associated Macrophages |
Nov 2012 |
16 pages |
| Authors:
John Maher; KING'S COLL LONDON (UNITED KINGDOM)
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| The hypothesis underlying this synergistic partnership award was that immunotherapy of epithelial ovarian carcinoma (EOC) with chimeric antigen receptor (CAR)-expressing T-cells would be potentiated if simultaneous targeting of tumor cells and tumor-associated macrophages (TAM) was achieved. To test this hypothesis, we initially engineered T-cells to express CARs with specificity for MUC1 (expressed by tumor cells) and CSF-1R (expressed both by tumor cells and TAM). In-vitro experiments demonstrated some efficacy of ... |
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| Human Neural Cell-Based Biosensor |
31 Oct 2012 |
5 pages |
| Authors:
Steven L Stice; Jamie Chilton; ARUNA BIOMEDICAL INC ATHENS GA
|
| The purpose of this project is to develop in vitro, cell based biosensors for environmental toxins. By using ArunA s neural cell lines derived from both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), our goal is to provide a human neural cell based biosensor that is a more biologically relevant model of human physiology. This report describes the progress made in these major areas: (1) ... |
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| HER4 Cyt1 and Cyt2 Isoforms Regulate Transcription through Differential Interaction with a Transcriptional Regulator, Yap |
Oct 2012 |
40 pages |
| Authors:
Anna M Misior; NORTH CAROLINA UNIV AT CHAPEL HILL
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| Our laboratory has previously shown that two isoforms of Epidermal Growth Factor Receptor family member, HER4: Cyt1 and Cyt2 exhibit opposing effects on mammary epithelial cells in vitro and in vivo. In our hands, Cyt1 attenuated growth and promoted differentiation, while Cyt2 promoted cell proliferation of mammary epithelial cells. The two isoforms differ by presence of additional 16 amino acids in Cyt1, which introduces a phosphoinositide- 3 kinase- and third ... |
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| Defining the Role of Post-Translational Modifications in SRC-3-Mediated Repression of mRNA Translation |
Oct 2012 |
22 pages |
| Authors:
Amber Johnson; BAYLOR COLL OF MEDICINE HOUSTON TX
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| Breast cancer is the most common, malignant cancer of women in North America; however, there are a number of criteria that determine the prognosis of each cancer. Breast cancer development and progression is influenced by gene expression patterns of both the tumor cells, as well as cells within the tumor microenvironment, such as macrophages. Steroid receptor coactivator 3 (SRC-3) is a molecule that has been shown to influence gene expression ... |
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| Targeting Breast Cancer with T Cells Redirected to the Vasculature. Addendum |
Oct 2012 |
11 pages |
| Authors:
George Coukos; PENNSYLVANIA UNIV PHILADELPHIA
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| The overall objective of this project is to develop targeted therapy tools directed against the breast cancer vasculature. We aim to bypass many obstacles in the field by developing a treatment based on the targeting of tumor blood vessels with T cells bearing chimeric immune receptors (CIRs). We have constructed and tested first generation CIR lentiviral vectors targeting hTEM1, which were derived from a panel of scFvs of varying affinity. ... |
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| Targeting Breast Cancer with T Cells Redirected to the Vasculature |
Oct 2012 |
11 pages |
| Authors:
Nathalie Scholler; George Coukos; Chunsheng Li; PENNSYLVANIA UNIV PHILADELPHIA
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| The overall objective of this project is to develop targeted therapy tools directed against the breast cancer vasculature. We aim to bypass many obstacles in the field by developing a treatment based on the targeting of tumor blood vessels with T cells bearing chimeric immune receptors (CIRs). We have constructed and tested first generation CIR lentiviral vectors targeting hTEM1, which were derived from a panel of scFvs of varying affinity. ... |
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| Optimizing the HRP-2 In Vitro Malaria Drug Susceptibility Assay Using a Reference Clone to Improve Comparisons of Plasmodium falciparum Field Isolates |
13 Sep 2012 |
20 pages |
| Authors:
Wiriya Rutvisuttinunt; Suwanna Chaorattanakawee; Stuart D Tyner; Paktiya Teja-isavadharm; Youry Se; Kritsanai Yingyuen; Panjaporn Chaichana; Delia Bethell; Douglas S Walsh; Chanthap Lon; ARMED FORCES HEALTH SURVEILLANCE CENTER SILVER SPRING MD
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| Apparent emerging artemisinin-resistant Plasmodium falciparum malaria in Southeast Asia requires development of practical tools to monitor for resistant parasites. Although in vitro anti-malarial susceptibility tests are widely used, uncertainties remain regarding interpretation of P. falciparum field isolate values. |
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| The Role of microRNA miR-101 in Prostate Cancer Progression |
Sep 2012 |
98 pages |
| Authors:
Qi Cao; MICHIGAN UNIV ANN ARBOR
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| Polycomb group (PcG) proteins are chromatin-modifying complexes that regulate epigenetic silencing and play an important role in determining cell fate. PcG proteins form two major complexes, Polycomb repressive Complex 1 (PRC1) and Polycomb repressive Complex 2 (PRC2). PRC2 methylates histone H3 on lysin 27 (H3K27) creating a chromatin mark which stimulates PRC1 to enact gene silencing at target genes. Employing in vitro and in vivo cancer models, combined with human ... |
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| Bio-Physicochemical Interactions of Engineered Nanomaterials in In Vitro Cell Culture Model |
14 Aug 2012 |
24 pages |
| Authors:
Paramjit Grover; M F Rahman; M Mahboob; INDIAN INST OF CHEMICAL TECHNOLOGY HYDERABAD
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| A study on the physicochemical properties and MTT cytotoxicity assay of cerium oxide (CeO2), cobalt oxide (Co3O4) and tungsten oxide (WO3) nanomaterials (NMs) on different cell lines was carried out during the last year. The physicochemical properties like size, size distribution, state of dispersion and zeta potential of these NMs are the important factors to study their toxicity. |
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| iPSC-Derived MSCs that Are Genetically Engineered for Systemic Bone Augmentation |
Aug 2012 |
18 pages |
| Authors:
Xiaobing Zhang; LOMA LINDA UNIV CA
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| Mesenchymal stem cells (MSCs) differentiated from Induced pluripotent stem cells (iPSCs) have a potential application in clinic to treat osteoporosis and other skeletal diseases. Further engineering MSCs with homing factors like CXCR4 and osteogenic factors like shNoggin or FGF2 may increase the therapeutic effects. Toward these goals, we have generated iPSCs using lentiviral vectors from blood cells and integration-free iPSCs using episomal vectors. The generated iPSCs are pluripotent, as evident ... |
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| Diversity and Biological Activities of Endophytic Fungi Associated with Micropropagated Medicinal Plant Echinacea purpurea (L.) Moench |
Aug 2012 |
12 pages |
| Authors:
Luiz H Rosa; Nurhayat Tabanca; Natascha Techen; David E Wedge; Zhiqiang Pan; Ulrich R Bernier; James J Becnel; Natasha M Agramonte; Larry A Walker; Rita M Moraes; AGRICULTURAL RESEARCH SERVICE GAINESVILLE FL CENTER FOR MEDICAL AGRICULTURAL AND VETERINARY ENTOMOLOGY
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| Echinacea is one of the top ten selling medicinal herbs in Europe and United States. Commercially available formulations may contain different plant parts of three species (Echinacea purpurea, E. pallida, and E. angustifolia). Our study evaluates the diversity of microbial community associated with healthy E. purpurea clones and their ability to produce defense compounds. We recovered and identified thirty-nine fungal endophytes through the molecular methods in 15 distinct phylotypes, which ... |
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| 5-AED Enhances Survival of Irradiated Mice in a G-CSF-Dependent Manner, Stimulates Innate Immune Cell Function, Reduces Radiation-Induced DNA Damage and Induces Genes that Modulate Cell Cycle Progression and Apoptosis |
22 Jul 2012 |
16 pages |
| Authors:
Marcy B Grace; Vijay K Singh; Juong G Rhee; III Jackson William E; Tzu-Cheg Kao; Mark H Whitnall; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
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| The steroid androst-5-ene-3beta,17beta-diol (5-androstenediol, 5-AED) elevates circulating granulocytes and platelets in animals and humans, and enhances survival during the acute radiation syndrome (ARS) in mice and non-human primates. 5-AED promotes survival of irradiated human hematopoietic progenitors in vitro through induction of Nuclear Factor-kappaBeta (NFkappaBeta)-dependent Granulocyte Colony- Stimulating Factor (G-CSF) expression, and causes elevations of circulating G-CSF and interleukin-6 (IL-6). However, the in vivo cellular and molecular effects of 5-AED are ... |
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| Human Neural Cell-Based Biosensor |
05 Jul 2012 |
4 pages |
| Authors:
Steven L Stice; Jamie Chilton; ARUNA BIOMEDICAL INC ATHENS GA
|
| The purpose of this project is to develop in vitro, cell based biosensors for environmental toxins. By using ArunA s neural cell lines derived from both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), our goal is to provide a human neural cell based biosensor that is a more biologically relevant model of human physiology. This report focused on the differentiation of hESC- and hiPSC-derived neural ... |
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| Development of a Tetrathioether (S4) Bifunctional Chelate System for Rh-105 |
Jul 2012 |
9 pages |
| Authors:
Valerie Carroll; Don Wycoff; Fabio Galazzi; Timothy Hoffman; Silvia Jurisson; MISSOURI UNIV-COLUMBIA
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| The purpose of this project is to develop and evaluate a potential new molecule for site directed prostate cancer therapy. The moderate - emissions (0.566 MeV [70%], 0.248 MeV [19%], t = 35.4 h) of rhodium-105 are well suited for therapy of solid tumors. In addition to its favorable nuclear properties, the kinetic inertness of low-spin d6 Rh(III) complexes make them good candidates for radiopharmaceutical use. The bifunctional chelate method ... |
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| Interaction of Synuclein and Inflammation in Dopaminergic Neurodegeneration |
Jul 2012 |
8 pages |
| Authors:
Serge Przedborski; Vernice Jackson-Lewis; COLUMBIA UNIV NEW YORK
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| Parkinson Disease (PD) is the second most common neurodegenerative disease of our aged population behind Alzheimer s Disease. Epidemiological, animal and cell culture studies have shown that inflammation is a part of the PD morphological picture. It has been suggested that -synuclein (a major component of the Lewy bodies present within dopamine neurons of the PD substantia nigra {SN}) is responsible for the observed inflammatory response in the PD brain. ... |
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| ICBP90 Regulation of DNA Methylation, Histone Ubiquitination, and Tumor Suppressor Gene Expression in Breast Cancer Cells |
Jul 2012 |
9 pages |
| Authors:
Molly S Shook; Elena N Cravens; Erika J Hughes; Scott A Coonrod; Eric J Richards; CORNELL UNIV ITHACA NY
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| In mammals and other higher eukaryotes, SRA-RING proteins are essential for global maintenance of DNA methylation. This research project focuses on the discovery of new ubiquitination targets for the Arabidopsis SRA-RING protein VIM1 and the human SRA-RING protein UHRF1. Additionally, it will closely examine the methylcytosinebinding specificity of UHRF1, with a specific focus on non-CpG contexts. The proposed work is ongoing, and so far the major accomplishments include creation of ... |
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| Non-thermal High-intensity Focused Ultrasound for Breast Cancer Therapy |
Jul 2012 |
17 pages |
| Authors:
Chang M Ma; FOX CHASE CANCER CENTER PHILADELPHIA PA
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| 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 ... |
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| Preclinical Investigations of a Novel Small Molecule Radiosensitizer of Prostate Cancer |
Jul 2012 |
6 pages |
| Authors:
Brian Lally; MIAMI UNIV FL
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| The radiation therapy (RT) has proven to be effective at increasing survival of men with prostate cancer. However, the results are far from optimal, with 30-40% of men with intermediate to high risk prostate cancer failing within 5 years. We have been investigating agents that have the potential to enhance the cell killing effects of one or both of these treatments. NS-123 is a drug that we have identified as ... |
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| Combinatorial Therapy Approaches for NF2-Deficient Meningiomas |
01 Jun 2012 |
21 pages |
| Authors:
Gilson S Baia; JOHNS HOPKINS UNIV BALTIMORE MD
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| The aim of our research is to find novel targeted therapy for NF2 patients to provide a new therapeutic option for meningiomas that includes the standard of care radiotherapy. During the first year if this project we have successfully selected four small molecule compounds that preferentially inhibit NF2 mutant meningioma cells in vitro. These are FDA approved drugs that are safe for human use. We validated these drugs by using ... |
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| Role of NuSAP in Prostate Tumor Progression |
Jun 2012 |
18 pages |
| Authors:
James D Brooks; LELAND STANFORD JUNIOR UNIV CA
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| We have identified NuSAP as prognostic marker upregulated in recurrent prostate tumors. Our grant aimed at identifying the role of NuSAP in promoting proliferation and invasion in Prostate Cancer and identify genes that upregulate NuSAP expression. To characterize the role and regulation of NuSAP in prostate cancer, we studied the expression of NuSAP in the LNCaP and PC3 human prostate cancer cell lines. Post-transcriptional silencing of the NuSAP gene severely ... |
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| Protein Phosphatase 2A Signaling in Human Prostate Cancer |
Jun 2012 |
10 pages |
| Authors:
Ajay Singh; UNIVERSITY OF SOUTH ALABAMA MOBILE
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| Advanced prostate cancers (PCa) treated with first line androgen-deprivation therapy (ADT) eventually relapse in a hormone refractory or castration-resistant (CR) form. Relapsed disease is highly aggressive and poses an increased risk of morbidity and death. Previously, we demonstrated that PPP2CA, which encodes the catalytic-subunit (alpha-isoform) of the protein phosphatase 2A (PP2AC ), is downregulated in CR PCa. The level of PP2AC was decreased in majority of CR PCa cell lines ... |
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| Histone Code Modulation by Oncogenic PWWP-domain Protein in Breast Cancers |
Jun 2012 |
41 pages |
| Authors:
Zeng-Quan Yang; WAYNE STATE UNIV DETROIT MI
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| Amplification of 8p11-12 occurs in approximately 15% of human breast cancer (HBC), and this region of amplification is significantly associated with disease-specific survival and distant recurrence in breast cancer patients. Earlier, we used genomic analysis of copy number and gene expression to perform a detailed analysis of the 8p11-12 amplicon for identifying candidate oncogenes in breast cancer. We identified Wolf-Hirschhorn syndrome candidate 1-like 1 (WHSC1L1) as a candidate oncogene based ... |
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| Novel Synergistic Therapy for Metastatic Breast Cancer: Magnetic Nanoparticle Hyperthermia of the Neovasculature Enhanced by a Vascular Disruption Agent |
Jun 2012 |
18 pages |
| Authors:
Natalie L Adolphi; NEW MEXICO UNIV HEALTH SCIENCES CENTER ALBUQUERQUE HEALTH SCIENCES CENTER
|
| Vascular disruption agents (VDAs) have been shown to selectively destroy established tumor vasculature, which results in the ischemic death of up to 99% of tumor cells. The weakness of VDA monotherapy is that it often leaves a rim of surviving tumor cells which can then regrow and spread. The overall goal of this study (addressed in Task 2) is to enhance VDA therapy by inducing hyperthermia, targeted to the neovascular ... |
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| Commensal Gut Derived Anaerobes as Novel Therapy for Inflammatory Autoimmune Diseases |
May 2012 |
39 pages |
| Authors:
Ashutosh Mangalam; Veena Taneja; MAYO CLINIC ROCHESTER MN
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| Rheumatoid arthritis (RA) and multiple sclerosis (MS) are chronic inflammatory autoimmune diseases affecting millions of people. Here we are proposing a novel approach to cure MS, by administration of a specific strain of human commensal bacteria. Recent studies have shown that intestinal microflora plays an important role in the health of the host and posses probiotics like qualities. We hypothesize that Gram-negative commensal bacteria from human gut have the potential ... |
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| Commensal Gut-Derived Anaerobes as Novel Therapy for Inflammatory Autoimmune Diseases |
May 2012 |
12 pages |
| Authors:
Veena Taneja; MAYO CLINIC ROCHESTER MN
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| Predisposition to rheumatoid arthritis (RA) is associated with the presence of genetic factors, HLA class II molecules, DR4 and DQ8, being the strongest. Patients with RA show an imbalance of gut microbiota suggesting its role in regulation of disease. We have used HLA-DR4/ DQ8 mice to test our hypothesis that treatment with commensal bacteria like Prevotella histicola can modulate Collagen-induced arthritis (CIA). In vitro study showed that treatment of mice ... |
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| Specific PET Imaging Probes for Early Detection of Prostate Cancer Metastases |
May 2012 |
21 pages |
| Authors:
Xiankai Sun; TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER
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| Cell permeable peptide is considered as an efficient delivery system to cross the cell membrane barrier. However, the underlying mechanisms are very complicated. Through this project, we found that laminin receptor is one of initial binding site(s) responsible for R11 peptide uptake in prostate cells. Towards the goal of developing R11 for specific prostate cancer detection, we have successfully developed an approach to impart multivalency to a bifunctional chelator for ... |
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| Role of Cyclin E as an Early Event in Ovarian Carcinogenesis |
Apr 2012 |
59 pages |
| Authors:
Christine Walsh; CEDARS-SINAI MEDICAL CENTER LOS ANGELES CA
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| At the genetic level, ovarian cancer is characterized by a large degree of genetic instability. High copy-number amplification at the CCNE1 (cyclin E) gene locus is the single most notable recurrent change, occurring in about 20% of tumors. We have hypothesized that CCNE1 gene amplification is an initiating event in the carcinogenic process of a subset of epithelial ovarian cancers. We have made progress towards testing our hypothesis of cyclin ... |
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| Role of Inflammation and Insulin Resistance in Mouse Models of Breast Cancer |
Apr 2012 |
9 pages |
| Authors:
Jerrold Olefsky; CALIFORNIA UNIV SAN DIEGO LA JOLLA
|
| We have shown that obesity increases tumor burden without significantly altering tumor morphology suggesting that the primary effect of obesity is on tumor cell proliferation. Interestingly, the origin of the obesity did not have an effect as genetic obesity due to leptin mutation or diet-induced obesity due to a high fat western diet equivalently increased tumor growth. While there was no difference in macrophage infiltration into the tumors themselves, we ... |
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| Heparanase Mechanisms in Brain - Metastatic Breast Cancer |
Apr 2012 |
10 pages |
| Authors:
Dario Marchetti; BAYLOR COLL OF MEDICINE HOUSTON TX
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| 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 ... |
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| Production Methods for a Mesenchymal Stem Cell Therapeutic as a Medical Defense Countermeasure |
Feb 2012 |
26 pages |
| Authors:
Timothy R Varney; Christopher M Bowens; Jr Eaton Erik B; III Lehman John G; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| The application of cellular therapies to treat battlefield injuries offers a novel and promising approach to address longstanding challenges in the repair of tissue damage with regard to both structural and functional improvement. The results of currently published investigations describing mesenchymal stem cell (MSC) efficacy in a variety of injury models demonstrate the unique qualities of this reparative cell population to adapt to the requirements of the damaged tissue in ... |
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| Molecular Characterization of Human MUC16 (CA125) in Breast Cancer |
Feb 2012 |
11 pages |
| Authors:
Srustidhar Das; NEBRASKA UNIV MEDICAL CENTER OMAHA
|
| The proposed study was aimed at understanding the role of MUC16 cytoplasmic tail (MUC16CT) in MUC16 mediated breast cancer pathogenesis and progression. To achieve this we proposed to understand the role of MUC16CT by carrying out over expression of MUC16CT in BC cells followed by performing various established in vitro and in vivo functional studies. To this end, we have generated FLAG-tagged MUC16CT-114FL and 114dCT stable transfectants in MDAMB231 and ... |
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| The Isolation and Characterization of Human Prostate Cancer Stem Cells |
Feb 2012 |
14 pages |
| Authors:
Ganesh Palapattu; METHODIST HOSPITAL HOUSTON TX
|
| The overall objective of this proposal is to develop a durable cure for lethal prostate cancer through the elucidation of the role of cancer stem cells in the pathogenesis of the disease. During the past year, we have made the following significant findings/observations: i)3D culture of human prostate cancer cells with magnetic nanoparticles is not optimal for tumor initiation studies, ii) in vitro co-culture of human prostate cancer cells (established ... |
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| Early Breast Lesion Typing With Hyperpolarized Choline, Benign Or Malignant |
Feb 2012 |
8 pages |
| Authors:
Shawn Wagner; CEDARS-SINAI MEDICAL CENTER LOS ANGELES CA
|
| This work is focused on developing a breast cancer biomarker utilizing magnetic resonance spectroscopy/imaging and hyperpolarization. I have initiated and completed most of the elements in the first part of the project which consist of developing the equipment and the biomarker agent. Task 2-4 required the completion of Task 1. The most significant achievement is the completion of the required equipment and initial testing. We have developed a fully functional ... |
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| Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation |
Feb 2012 |
16 pages |
| Authors:
W P Lee; JOHNS HOPKINS UNIV BALTIMORE MD
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| Composite Tissue Allotransplantation (CTA) offers an alternative reconstructive strategy for complicated musculoskeletal injuries incurred during modern warfare where functional outcomes after multipe conventional reconstructions are suboptimal. Broader clinical application of CTA, however, continues to be hampered by requirement for long-term multi-drug immunosuppression to prevent graft rejection. Furthermore, unlike in solid organs, clinical success is dictated not only by graft acceptance, but also by functional outcome. Our study proposes a novel ... |
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| Assessments of Tumor Extracellular pH with PARACEST MRI |
Jan 2012 |
57 pages |
| Authors:
Vipul R Sheth; CASE WESTERN RESERVE UNIV CLEVELAND OH
|
| In this research project an approach to measure pH by Chemical Exchange Saturation Transfer (CEST) MRI is developed. We describe the characterization of a PARACEST MRI contrast agent, Yb-DO3A-oAA, for pH measurement. The pH measurement is independent of concentration and T1sat relaxation times, and covers a wider pH measurement range than alternative methods. We also developed a new method for fitting PARACEST. To simplify MRI acquisition of CEST spectra a ... |
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| Metabolic Activation of Sulfur Mustard Leads to Oxygen Free Radical Formation |
Jan 2012 |
8 pages |
| Authors:
A A Brimfield; S D Soni; K A Trimmer; M A Zottola; R E Sweeney; J S Graham; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| We recently published electron paramagnetic resonance (EPR) spin trapping results that demonstrated the enzymatic reduction of sulfur mustard sulfonium ions to carbon-based free radicals using an in vitro system containing sulfur mustard, cytochrome P450 reductase, NADPH, and the spin trap alpha-(4-pyridyl-1-oxide)-N-tertbutylnitrone (4-POBN) in buffer (A.A. Brimfield et al., 2009, Toxicol. Appl. Pharmacol. 234:128 134). Carbonbased radicals have been shown to reduce molecular oxygen to form superoxide and, subsequently, peroxyl and ... |
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| 5-AED Enhances Survival of Irradiated Mice in a G-CSF-Dependent Manner, Stimulates Innate Immune Cell Function, Reduces Radiation-induced DNA Damage and Induces Genes that Modulate Cell Cycle Progression and Apoptosis |
Jan 2012 |
16 pages |
| Authors:
Marcy B Grace; Vijay K Singh; Juong G Rhee; III Jackson William E; Tzu-Cheg Kao; Mark H Whitnall; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
|
| The steroid androst-5-ene-3beta,17beta-diol (5-androstenediol, 5-AED) elevates circulating granulocytes and platelets in animals and humans, and enhances survival during the acute radiation syndrome (ARS) in mice and non-human primates. 5-AED promotes survival of irradiated human hematopoietic progenitors in vitro through induction of Nuclear Factor-kappaB (NFkappaB)-dependent Granulocyte Colony-Stimulating Factor (G-CSF) expression, and causes elevations of circulating G-CSF and interleukin-6 (IL-6). However, the in vivo cellular and molecular effects of 5-AED are not ... |
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| In Vitro Osteoblast Model for Bone Wound Infections and Antimicrobial Therapy |
Dec 2011 |
16 pages |
| Authors:
Chrysanthi Paranavitana; GENEVA FOUNDATION TACOMA WA
|
| We proposed to determine the changes in osteoblast differentiation in vitro when infected with multidrug resistant bacteria and the therapeutic effects of two well characterized antimicrobial peptides. For the first part of the study, an in vitro 3 dimensional (3D) model of primary human osteoblasts in a collagen scaffold was developed for infection. The 3D osteoblast cultures were infected with clinical isolates of multidrug resistant Acinetobacter baumannii, Klebsiellapneumoniae and Pseudomonas ... |
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| Human Neural Cell-Based Biosensor |
11 Oct 2011 |
9 pages |
| Authors:
Steven L Stice; Jamie Chilton; Allan Powe; ARUNA BIOMEDICAL INC ATHENS GA
|
| Human neural progenitors have a strong potential for use as cell-based biosensors for environmental toxins. Here, we report the following accomplishments in developing a neural cell-based biosensor. (1) We developed iPSC equivalents for the ESC-derived hNP1 neural progenitor and hN2 mixed neuronal cell lines, giving us the capability to create disease-specific neural cells from patient fibroblasts. (2) We continue to optimize our novel approach for hNP1 differentiation into dopaminergic neurons ... |
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| Functional Genomics for Epithelial-Mesenchymal Transition in Breast Cancer |
Oct 2011 |
40 pages |
| Authors:
Erik Thompson; MELBOURNE UNIV PARKVILLE (AUSTRALIA)
|
| To assess whether modulation of the PMC42-LA cell line by a library of shRNAmir constructs can cause tumorigenicity, the impact of a smaller boutique library is first being assessed, as proposed. This boutique library of 4,462 shRNA constructs targeting 1,860 markers and mediators of EMT, metastasis, migration, and BCSC has been transduced into the PMC42-LA cell line as a total pool and as ten smaller sub-pools. These were expanded in ... |
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| ERbB2 Trafficking and Signaling in Human Vestibular Schwannomas |
Oct 2011 |
59 pages |
| Authors:
Marlan R Hansen; IOWA UNIV IOWA CITY
|
| We find that the ErbB2 receptor tyrosine kinase is active in vestibular schwannoma (VS) cells and drives proliferation. Our overall hypothesis is that defects in merlin lead to constitutive ErbB2 activation at the cell membrane and that inhibition of ErbB2 will reduce the survival of VS cells and potentiate the effects of radiation on VSs. In this report we show that VS cells, which lack functional merlin, constitutively express activated ... |
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| The AIF/XIAP Axis in Prostate Cancer |
Oct 2011 |
16 pages |
| Authors:
John Wilkinson; WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF HEALTH SCIENCES
|
| Over the funding period substantial progress was made towards completion of the project goals described in the original statement of work. AIF deficient PC3 cells were established and used to demonstrate that AIF does not affect the in vitro growth of these cells but is critical for growth of these cells in a xenograft model. These growth discrepancies manifest in both three dimensional cell culture growth and invasion assays, in ... |
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| Spinal Cord Repair with Engineered Nervous Tissue |
Oct 2011 |
10 pages |
| Authors:
Douglas H Smith; PENNSYLVANIA UNIV PHILADELPHIA
|
| Spinal cord injury (SCI) exacts an enormous social and financial burden on society. As such, there has been considerable attention directed at finding treatment strategies, including development of tissue and cell transplant techniques. However, the current approaches do not adequately address the complexity of the injury site, such as lesion length and an environment that is usually non-permissive for axon regeneration. We have developed tissue-engineered constructs consisting of living dorsal ... |
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| Identifying Breast Tumor Suppressors Using in Vitro and in Vivo RNAi Screens |
Oct 2011 |
19 pages |
| Authors:
Elizabeth Iorns; MIAMI UNIV FL
|
| Cancer is caused by mutations in oncogenes and tumor suppressor genes, resulting in the deregulation of processes fundamental to the normal behavior of cells. The identification and characterization of oncogenes and tumor suppressors has led to new treatment strategies that have significantly improved cancer outcome. The advent of next generation sequencing has allowed the elucidation of the fine structure of cancer genomes, however, the identification of pathogenic changes is complicated ... |
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| Chemically Modified Bacteriophage as a Streamlined Approach to Noninvasive Breast Cancer Imaging |
Oct 2011 |
22 pages |
| Authors:
Michelle E Farkas; CALIFORNIA UNIV BERKELEY
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| While capable of visualizing tumors with high sensitivity, current diagnostic imaging methods yield little information with regard to the type of cancer present; biopsy follow-ups are required to determine prognosis and treatment. As a non-invasive alternative, we directly convert cell surface marker-specific phage isolated from library screens into imaging agents that can target and differentiate breast cancer tissues. By using efficient synthetic protocols, we are able to selectively conjugate small ... |
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| A Better Way to Excise Inhibitory Molecules (CSPGs) from a Spinal Cord Injury Scar to Promote Regeneration |
Oct 2011 |
32 pages |
| Authors:
Diane Snow; Thomas M Hering; KENTUCKY UNIV LEXINGTON
|
| A major consequence of spinal cord injury (SCI) is the development of a glial scar. Although the scar has benefits for tissue repair, it also blocks neural regeneration. Inhibitory chondroitin sulfate proteoglycans (CSPGs) are elevated in the glial scar and are a major deterrent to successful regeneration. In the present study, we have demonstrated that injured astrocytes produce a wide variety of inhibitory CSPGs. To develop a more efficient method ... |
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| Signaling Through the PI 3-K, Akt, and SGK Pathway in Breast Cancer Progression |
Oct 2011 |
16 pages |
| Authors:
Sivan Elloul; BETH ISRAEL DEACONESS HOSPITAL INC BOSTON MA
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| The aggressive behavior of malignant breast cancer is determined by a complex array of signaling pathways that regulate cell growth, survival and migration. The PI 3-K-Akt pathway has been linked to all of these responses. The current paradigm states that deregulated PI 3-K-Akt signaling promotes cancer progression. Many of the enzymes that regulate PI 3-K signaling are frequently mutated in human breast cancer, thereby up-regulating Akt activity and increasing tumor ... |
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