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This award seeks to develop high-throughput optical metabolic imaging (OMI) of primary breast tumor organoids (three-dimensional cultures of tumors) to rapidly test/screen breast cancer therapeutics as a strategy to streamline drug development and provide individualized treatment. The results outlined in this progress report indicate that OMI in primary breast tumor organoids can provide early, sensitive measures of treatment response. This system can therefore be used to streamline...
Topics: DTIC Archive, Skala,Melissa C, VANDERBILT UNIV NASHVILLE TN NASHVILLE United States, Cancer...
In the prior period we obtained needed IACUC and biosafety approvals, and developed the backbone Listeria vector needed to produce the B7-H1 scFv and B7-H1-expressing Listeria vectors for follow up work. We demonstrated the significance of host B7-H1 in preventing/mitigating colitis and also colon cancer, suggesting that a B7-H1-expressing vector could be useful for clinical uses in colitis and cancer prevention. We generating a full PD-L1 KO cell line using CRISPR to optimize library screening...
Topics: DTIC Archive, Curiel,Tyler, University of Texas health Science Center at San Antonio San Antonio...
During this report period, we conducted both intravital imaging and whole tissue clearing based imaging to dissect the interaction between tumor cell and its brain metastatic microenvironment. We have successfully expanded GFAP-GFP mouse line (brain astrocyte specific) and performed preliminary testing on the intravital imaging capability. In addition, we have streamlined and optimized tissue-clearing pipeline. We are able to multiplex staining multiple tissue markers in situ, including brain...
Topics: DTIC Archive, Zhang,Siyuan, University of Notre Dame Notre Dame United States, breast cancer,...
Defense Technical Information Archive
by Defense Technical Information Center
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In this report we integrated the major results from our rat hemorrhagic shock model with the mechanistic details of protection from ischemia and reperfusion injury in hibernating mammals. Arousal from torpor during hibernation occurs rapidly, but there is no evidence of brain injury accompanying this extreme physiological transition. Production of the antioxidant melatonin accompanies arousal, suggesting that it plays a protective role at this time. We investigated the mechanism of melatonin...
Topics: DTIC Archive, Andrews,Matthew T, University of Minnesota Minnesota United States, hemorrhagic...
Defense Technical Information Archive
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This research study aims to expand the field of knowledge of Gulf War Illness. The research may provide initial proof of the innovative hypothesis that Gulf War Illness is related to low grade neuron-inflammation, which can be down regulated, by Naltrexone and Dextromethorphan. This is untested but potentially ground breaking concept that could provide, both an enhanced understanding of, and beneficial treatment for, Gulf War Illnesses. Research at the National Institute of Environmental Health...
Topics: DTIC Archive, Meggs,William J, East Carolina University Greenville United States, gulf war...
Defense Technical Information Archive
by Defense Technical Information Center
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The FDA-approved drug pirfenidone is an anti-inflammatory/anti-fibrosis drug indicated for pulmonary fibrosis that we hypothesize can diminish scarring when applied topically to deep partial-thickness burn wounds in two animal models. The long-term objective is to learn to effectively use pirfenidone with regard to dosage, formulation and timing of treatment of burn wounds, such that animal studies will likely translate to the clinic. The objective of this proposal is to evaluate pirfenidone...
Topics: DTIC Archive, Leung,Kai, The Geneva Foundation Tacoma United States, ANTIINFLAMMATORY AGENTS,...
Armed conflict between nations and groups usually requires those who fight to leave behind their families and loved ones. From the Greeks mounting their siege of Troy to the Greatest Generation preparing to enter World War II, the three phases of the deployment cyclepreparation, separation, and reintegrationhave been a regular part of military life throughout the ages. Although many service members anticipate deployments, eager for the opportunity to defend their country and utilize their...
Topics: DTIC Archive, Meadows,Sarah O, RAND Arroyo Center Santa Monica United States, military personnel,...
Defense Technical Information Archive
by Defense Technical Information Center
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Atypical antipsychotics (AAP) are prescribed to millions of patients with neuropsychiatric disorders. Although AAP can ameliorate mental dysfunctions, they have serious metabolic side-effects such as weight gain, the metabolic syndrome, and increased risk of diabetes and cardiovascular disease. The current dogma is that the metabolic side effects of AAP are attributed to their action on neuronal circuits the brain. However, we discovered expression of functional dopamine and serotonin receptors...
Topics: DTIC Archive, Ben-Jonathan,Nira, University of Cincinnati Cincinnati United States, autism,...
Defense Technical Information Archive
by Defense Technical Information Center
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Lymphangioleiomyomatosis (LAM) is a rare disease in which tumor cells (LAM cells) proliferate and destroy healthy lung tissue, leading to respiratory compromise or failure. Vascular endothelial growth factor-D (VEGF-D) is generated by LAM cells and is a robust biomarker for LAM disease activity and therapeutic response. Studies in the laboratory of Dr. D'Armiento suggest that imatinib mesylate (imatinib) could completely block the growth of LAM cells through initiation of targeted cell death....
Topics: DTIC Archive, Strange,Charlie, Medical University of South Carolina Charleston United States,...
Prostate cancer is commonly multiclonal, meaning that most men with prostate cancer have multiple, genetically distinct cancers. Pathologists cannot assess clonally by routine microscopic evaluation, and hence multiclonality is not incorporated into routinely reported pathological parameters, such as the number of cores with cancer. Given the importance of routine pathological parameters in prostate cancer prognosis, the potential to refine these parameters through assessing multiclonality...
Topics: DTIC Archive, Tomlins,Scott A, Regents of the University of Michigan Ann Arbor United States, gene...
Breast cancer is a devastating disease that affects both women and men, and despite many advancements it is still often deadly and remains incurable when metastatic. Efficient novel treatments, or enhancements to current ones, are desperately needed to improve breast cancer therapy and to extend the lives of patients. Therefore, the overall goal of this proposal is to develop a tumor-specific, safe and effective therapy for breast cancer. We concentrate on HER2-overexpressing tumors, which are...
Topics: DTIC Archive, Dziegielewski,Jaroslaw, VIRGINIA UNIV CHARLOTTESVILLE CHARLOTTESVILLE United States,...
This research investigates the extent to which regular walking in an exoskeleton will provide mobility, health, and recovery benefits to individuals with spinal cord injury. The research is comprised of three sub-studies. The first investigates prospective benefits while walking in an exoskeleton; the second investigates prospective additional benefits when the exoskeleton is supplement with lower limb functional electrical stimulation; and the third investigates prospective benefits during...
Topics: DTIC Archive, Goldfarb,Michael, Vanderbilt University Nashville United States, spinal cord,...
The overall objective of this research effort is to identify biomarkers following articular fracture that may be predictive of the development of post-traumatic arthritis (PTA). PTA is a clinically important complication of joint injury with life-long effects for the patient. While PTA can occur rapidly after moderate to severe articular injuries, not every patient will go on to develop this condition. There are no effective screening methods to determine who is at risk. This proposal includes...
Topics: DTIC Archive, Olson,Steven A, Duke University Durham United States, wounds and injuries, xray...
Defense Technical Information Archive
by Defense Technical Information Center
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The objective of this project is to discover and characterize molecules that inhibit breast cancer cell proliferation by maintaining activity of the retinoblastoma protein (Rb). Rb is inactivated to drive proliferation in normal and cancer cells by phosphorylation, which dissociates the E2F transcription factor from Rb. Our goal is to find and characterize molecules that stabilize the complex between phosphorylated Rb and E2F.
Topics: DTIC Archive, Rubin,Seth M, University of California, Santa Cruz Santa Cruz United States, breast...
Defense Technical Information Archive
by Defense Technical Information Center
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Arylimidamide compound DB766D was tested in combination with posaconazole in combination based on the premise that the partial efficacy provided by each compound individually would provide cures when the combination was dosed together. At the maximum tolerable dose of the combined treatment, efficacy was observed, however, no cures of L. major lesions were observed. Three additional compounds, DB2342, DB2332, and DB2336 were tested for potency against Leishmania in vitro, and as all 3 were very...
Topics: DTIC Archive, Hickman,Mark R, The Geneva Foundation Tacoma United States, ANTILEISHMANIAL DRUGS,...
Defense Technical Information Archive
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During this eighth year of the project, we completed the community consultation and public disclosure process in Baltimore. The results were submitted to the University or Maryland IRB, which has approved the trial. This approval included changing the local principal investigator to Dr. Tisherman with agreement from the Conflict of Interest Officer. We have also shifted the coordinating center for the study to the University of Maryland. Appropriate documents were subsequently submitted to the...
Topics: DTIC Archive, Kochanek,Patrick, University of Pittsburgh Pittsburgh United States, therapeutics,...
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This study will evaluate Constraint-Induced Movement (CI) therapy for promoting motor recovery in veterans and civilians with traumatic brain injury (TBI). This form of physical rehabilitation has been shown to substantially improve motor function after brain injury not due to trauma and to provoke a widespread neuroplastic response in the brain. This study (N =80) is a single blind, randomized controlled trial that compares CI therapy for improving use of the more-affected arm in adults with...
Topics: DTIC Archive, Taub,Edward, University of Alabama at Birmingham Birmingham United States, brain...
Defense Technical Information Archive
by Defense Technical Information Center
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Our project will establish the role of CDK5 in promoting the immunosuppressive microenvironment in prostate cancer, and identify optimal strategies for incorporation of CDK5 inhibition to augment the efficacy of immunotherapy for prostate cancer. We will confirm our observation of the involvement of a T cell antitumor response in impaired growth of prostate cancer in immunocompetent murine models of prostate cancer, and characterize the changes induced in immune cells in the tumors. Preclinical...
Topics: DTIC Archive, Nelkin,Barry, JOHNS HOPKINS UNIV BALTIMORE MD BALTIMORE United States, medical...
Defense Technical Information Archive
by Defense Technical Information Center
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The proposal was designed to address three issues. First could we identify stem cells fromthe fallopian tube, including from patients with high grade serous cancer (HGSC). Second,could we link the molecular abnormalities in cancer associated stem cells and validate themin pathologic material, specifically in what we feel are stem cell outgrowths or SCOUTs andthird could we identify molecular alterations that would place the oviduct or the patient atrisk for HGSC. In essence we wished to drill...
Topics: DTIC Archive, Crum,Christopher P, The Brigham and Women's Hospital, Inc Boston United States, stem...
Subject: Primary and acquired resistance to abiraterone and enzalutamide represent critical problems in contemporary prostate cancer clinical care, and development of predictive biomarkers of response and resistance to abiraterone and enzalutamide remains an urgent and unmet need. Purpose: The overall goal of this Biomarker Development Award proposal is to enable near-term clinical use of a noninvasive test for prediction and assessment of response to abiraterone and enzalutamide in men with...
Topics: DTIC Archive, Plymate,Stephen, University of Washington Seattle United States, prostate cancer,...
The purpose of this study is to compare the effectiveness of a porcine collagen matrix (CM), with or without the addition of enamel matrix derivative (EMD) in the treatment of Miller Class I, II or III recession defects. This will be a prospective, single-blinded, randomized, split-mouth study. One defect will receive CM+EMD (test), while the other will receive CM (control) alone. MethodsThe treatment of 30 similarly sized Miller class I, II or III recession defects on single-rooted teeth using...
Topics: DTIC Archive, Barth,Christopher T, Uniformed Services University of the Health Sciences Bethesda...
Tuberculosis (TB) is still a major public health concern worldwide and, according to the World Health Organization (WHO), in 2013 there were an estimated 9 million new cases of TB. On the other hand, it is widely recognized that the burden of TB is often greater in urban than rural settings, both in developing and industrialized countries. This fact is certainly true in Latin America and the Caribbean (LAC) and in Peru too. Lima - the capital of Peru - has twenty-five percent of the countrys...
Topics: DTIC Archive, Escate,Cesar M, UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD BETHESDA...
Defense Technical Information Archive
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Purpose: The purpose of this study was to evaluate the level of provider compliance with oral cancer screenings as mandated by the DoD Dental Procedure codes D0120, D0150, and D0180,and to make a basic assessment of provider training and comfort in performing oral cancer screenings. Methods: This study employed a one-tailed online survey that provided descriptive information about the presence or absence of compliance with oral cancer screenings as well as the feeling of competence to complete...
Topics: DTIC Archive, Richards,Cory D, Uniformed Services University of the Health Sciences Ft. Hood United...
Pemetrexed(PEM), a standard therapy for non-squamous non-small cell lung cancer (NSCLC), inhibits the de novo thymidine pathway, resulting in a transient burst of metabolism through the salvage pathway, an effect detected as a flare of activity by 18F-thymidine (FLT)-PET. FLT is a reliable biomarker of proliferation, and post-therapeutic changes in tumor FLT avidity predicts therapeutic response in a range of malignancies. However, FLT as a measure of therapeutic response in NSCLC is not well...
Topics: DTIC Archive, Katz, Sharyn I, University of Pennsylvania Perelman School of Medicine Philadelphia...
Defense Technical Information Archive
by Defense Technical Information Center
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Through PEPFAR and DoD resources, the US Department of Defense provides the worlds largest source of HIV assistance to militaries and works with a worldwide cadre of military HIV experts to combat the harm that HIV inflicts on the health and readiness of the worlds military populations. Encouraging sustainability through the development of local capacity and expansion of facilities remains an important priority for DHAPP.
Topics: DTIC Archive, Hess,Stephanie, NAVAL HEALTH RESEARCH CENTER SAN DIEGO CA SAN DIEGO United States,...
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by Defense Technical Information Center
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We created new molecular-genetic expression vectors for efficient, non-invasive diagnosis and targeted radiopharmaceutical therapy of prostate cancer (PC). The diagnosis vector consists of the tumor-specific PEG-promoter (PEG-Prom) and cDNA of human chorionic gonadotropin beta chain (betahCG) as a reporter. We showed that transfection of the diagnostic vector to PC cells successfully produced detectable betahCG in the media by over-the-counter pregnancy kit and ELISA. We also showed that...
Topics: DTIC Archive, Pomper,Martin, Johns Hopkins UniversityBaltimore Baltimore United States, prostate...
Defense Technical Information Archive
by Defense Technical Information Center
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Our preliminary data strongly suggest that BMI1 is a master regulator of castration-resistant prostate cancer (CRPC) progression. Our objective is to determine how BMI interacts with epigenetic complexes and with AR to regulate tumor suppressor gene expression. We aim to identify novel binding partners and regulators of oncogene expression, which will lead to a better understanding of AR signaling and dysfunction. Specifically, we will identify how BMI1 and PRC1 proteins mediate their oncogenic...
Topics: DTIC Archive, Cao,Qi, Methodist Hospital Research Institute Houston United States, prostate cancer,...
Defense Technical Information Archive
by Defense Technical Information Center
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The goal of this project is to develop a novel means to inhibit prostate cancer development and progression. The development of Siah1/2 inhibitors to the ubiquitin ligase Siah1/2 has been advanced by the ability to develop a Siah1/2 inhibitory peptide that effectively inhibits Siah1/2 activity, which was found to effectively attenuate the growth of prostate cancer tumors in vivo when transplanted subcutaneously or orthotopically into the prostate site. The assessment of the Siah1/2 inhibitory...
Topics: DTIC Archive, Ronai,Ze'ev, Sanford-Burnham-Prebys Medical Research Institute La Jolla United...
Defense Technical Information Archive
by Defense Technical Information Center
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The reentry of service members back into family life after deployment can be extremely challenging for military couples. Understanding the factors that contribute to the reintegration difficulty of returning service members and at-home partners is essential for attracting, retaining, and safeguarding the nations best military personnel. The goal of this project is to evaluate how peoples mental health symptoms and romantic relationship characteristics predict their difficulty with...
Topics: DTIC Archive, Knobloch,Leanne K, University of Illinois Urbana United States, military personnel,...
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by Defense Technical Information Center
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The goal of the Mississippi prostate cancer HBCU Undergraduate Research Training Program is to promote interest in careers in PCa research and care among undergraduate students from Tougaloo College (TC) and Jackson State University (JSU) at the University of Mississippi Medical Center (UMMC)-Cancer Institute (CI). During the summer of 2016, 2 undergraduate scholars from TC and JSU, gained experience in performing PCa research at UMMC-CI. This number added to trainees from classes of 2014 and...
Topics: DTIC Archive, Gomez,Christian, University Of Mississippi Medical Center Jackson United States,...
Defense Technical Information Archive
by Defense Technical Information Center
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This research is aimed at developing a new endoscopic imaging approach, called photoacoustic microscopy (PAM), for lung cancer staging. The project will develop imaging hardware and conduct phantom experiments to achieve the proposed goals. We have fulfilled the statement of work proposed. In Year 1, we characterized and optimized the proposed liquid acoustic lens for tunable photoacoustic imaging; we designed and optimized the housing of the endoscope, and conducted some initial phantom...
Topics: DTIC Archive, Jiang,Huabei, University of Florida Verobeach United States, photoacoustic...
A commonly used antifungal, Itraconazol targets a pathway that is also upregulated in human prostate cancer. It was observed that Itraconazol synergizes with cyclopamine to induce superior therapeutic effects. Cyclopamine is toxic, however, when combined with itraconazol the dose requirement for each drug was considerably reduced. This combination therefore has the potential to be more effective and at the same time less toxic. The most important aspect of this finding is that these are...
Topics: DTIC Archive, Mukhtar,Hasan, University of Wisconsin System Madison United States, antifungal...
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Why did we choose the topic, Beyond the Diagnosis? Why do people respond differently to a diagnosis? We want to ask that question. Why is an algorithmic approach not efficacious for all? Why is non-compliance so readily observed in our patients, and what do we do with it? Recently, I heard a story from one of my grandchild's classes that illustrates an important point. The teacher asked each child to draw a picture, and the teacher walked by and asked, Who are you drawing a picture of? The...
Topics: DTIC Archive, Wain,Harold J, WALTER REED NATIONAL MILITARY MEDICAL CENTER BETHESDA MD BETHESDA,...
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The goal of my DOD-supported research is to determine the role of the new mTOR complexes (mTORC1 and mTORC2) in Autism Spectrum Disorder (ASD). Individuals with ASD exhibit impaired social interactions, repetitive abnormal repetitive behavior as well as cognitive problems. In addition, a large proportion of ASD individual suffer from seizures. Autism is a heritable genetically heterogeneous disorder and mutations in the negative regulator of the mammalian target of rapamycin (mTOR) signaling...
Topics: DTIC Archive, Costa-Mattioli,Mauro, Baylor College of Medicine Houston United States, AUTISM,...
Sepsis is associated with a mortality of nearly 30%. Mortality is due, in part, to an uncontrolled inflammatory response. Matrix metalloproteinase-9 (MMP-9) and heat shock protein 70 (HSP 70) have been suggested to be biomarkers of severe sepsis and may be useful indicators of treatment success. Hydroxocobalamin (HOC), which regulates inducible nitric oxide synthase and increases systemic vascular resistance, may be effective in treating sepsis-induced hypotension and reversing overexpression...
Topics: DTIC Archive, Maddry, Joseph K, 59th Medical Wing Lackland AFB United States, sepsis, inflammation,...
Traumatic optic neuropathy (TON) is a common injury following traumatic insult to the head. A novel animal model of TON will be investigated for the purpose of developing diagnostics and treatments for TON. Magnetic resonance imaging techniques were developed to characterize retinal blood flow, axonal transport within the optic nerve, and functional imaging to allow diagnosis of TON. Matrix assisted laser desorption/ionization techniques have been developed to detect spatially resolved mass...
Topics: DTIC Archive, Reilly,Matthew A, University of Texas at San Antonio San Antonio United States,...
Topics: DTIC Archive, Shaw,Reuben J, The Salk Institute for Biological Studies La Jolla United States,...
Prostate cancer is the most common form of cancer in men with highly variable clinical response, reflecting the heterogeneity of the disease. Indeed, several recent studies have highlighted the molecular and genetic diversity among prostate cancers including a wide range of androgen receptor (AR) activity, which is the central axis of the disease. Interestingly AR activity did not show high correlation with AR mRNA or protein level in tumors, implicating other factors in this phenomenon. Given...
Topics: DTIC Archive, Lee,Eugine, Sloan -Kettering Institute for Cancer Research New York United States,...
Defense Technical Information Archive
by Defense Technical Information Center
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The Mental Health Advisory Team-Korea (8th Army) (referred to as MHAT-K8A elsewhere in this report) mission to Korea was requested by the Deputy Chief of Staff for US Forces-Korea (USFK) and coordinated with the USFK and 8th Army Surgeons and the 121st Combat Support Hospital. MHAT-K8A was the first assessment ever conducted in Korea or in the Pacific Command (PACOM). As in previous iterations of MHATs, (OIF, OEF) behavioral health researchers from the US Army Medical Research and Material...
Topics: DTIC Archive, US Army Medical Research Directorate-West Tacoma United States, health services,...
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This report summarizes the research progress and outcome of Traumatic optic neuropathy (TON). The report describes that TON as a vision-threatening complication in head injury in the war. Our goal is to develop an early therapeutic intervention before the progression of TON becomes irreversible. To achieve this goal, we tested the hypothesis that increase in the extracellular levels of adenosine can offer such an intervention. Under the stress of TON, extracellular levels of adenosine increase...
Topics: DTIC Archive, Liou,Gregory I, Georgia Health Sciences University Augusta United States, TRAUMA...
Hyperbaric Oxygen Therapy (HBO) is a treatment based on the respiration of high concentrations(up to 100%) of oxygen, while patients are exposed to high environmental pressures in a hyperbaric chamber. This treatment has been shown to be beneficial in a number of conditions/injuries, some of which are pertinent to military-type injuries. When administered timely and in a correct way, HBO improves the evolution and final outcome; however, because of the technical limitations of the treatment...
Topics: DTIC Archive, Science and Technology Organization Neuilly-sur-Seine Cedex France, wounds and...
Purpose: The hypothesis of this study is that EPI-001 that targets the AR NTD will inhibit AR-driven recurrence of prostate cancer resistant to current methods of androgen deprivation or blockade. Scope: Aim 1 will determine the impact of EPI-001 on castration sensitive tumor regression and re-growth in LuCaP xenografts and on growth of their castration resistant forms. Aim 2 will examine the impact of EPI-001 on castration sensitive and castration resistant growth of tumors with differing...
Topics: DTIC Archive, Plymate,Stephen R, University of Washington Seattle United States, clinical trials,...
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Acquired aplastic anemia (AA) is a fatal disorder characterized by immune-mediated destruction of hematopoietic stem and progenitorcells.1 Immunosuppressive therapy and allogeneic BMT have significantly improved the survival of severe AA.However, relapse still occurs in approximately 35 of AA patients when immunosuppressive therapy iswithdrawn.2,3 Furthermore, GVHD remains a major barrier to the success of allogeneic BMT.4,5 Memory T cells maypresent a significant barrier to the success of...
Topics: DTIC Archive, Zhang,Yi, Temple University Philadelphia, United States, lymphatic system,...
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The time from initiation of the project (15-July-2015) until the first experiments could be conducted (January, 2016) was devoted primarily to obtaining IACUC approval (October 30, 2015), the subsequent ACURO approval (December 31, 2015),hiring new personnel, conducting baseline testing for procedures not involving animals, testing equipment, developing detailed experimental design, conducting required training and testing of all personnel, and setting up all necessary accounts. Beginning in...
Topics: DTIC Archive, Adler,Martin W, Temple University of the Commonwealth System Philadelphia United...
The goal of this project is to develop intraventricular delivery of oncolytic HSV and to augment Dr. Friedman's training and education. The critical first step in developing this potential therapy is determining the cause of toxicity. In the first year, we determined that only active virus and not inactivated virus or vehicle caused toxicity, and virus was seen in the ependyma. We established the timing of the inflammatory response post-injection of the virus with a peak response seen at day 4...
Topics: DTIC Archive, Friedman,Gregory, The University of Alabama at Birmingham Birmingham United States,...
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This Physician Research Training Award supports a mentored training program integrated with a research project focused on the study of circulating tumor cells (CTCs) in prostate cancer patients using a microfluidic device (CTC-chip) to isolate CTCs from peripheral blood samples. During this award, we have developed a quantitative immunofluorescence assay to measure AR activity in single CTCs in patients with metastatic prostate cancer receiving treatment with hormonal therapy. We have also...
Topics: DTIC Archive, Miyamoto,David T, Massachusetts General Hospital Boston United States, prostate...
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by Defense Technical Information Center
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Obstructive sleep apnea (OSA) is a growing health concern in both civilian and military populations. Individuals who suffer from OSA have increased rates of cardiovascular disease, chronic fatigue, motor vehicle accidents, cognitive impairment, and post-traumatic stress disorder. Data from the Defense Medical Surveillance System (DMSS) were utilized to examine the incidence of OSA and associated attrition from service in active component military members from 1 January 2004 through 31 May 2016....
Topics: DTIC Archive, Rogers,Amy E, Armed Forces Health Surveillance Branch Silver Spring United States,...
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by Defense Technical Information Center
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The goal of this project is to develop a novel means to inhibit prostate cancer development and progression. The development of Siah1/2 inhibitors to the ubiquitin ligase Siah1/2 has been advanced by the ability to develop a Siah1/2 inhibitory peptide that effectively inhibits Siah1/2 activity, which was found to effectively attenuate the growth of prostate cancer tumors in vivo when transplanted subcutaneously or orthotopically into the prostate site. The assessment of the Siah1/2 inhibitory...
Topics: DTIC Archive, Bhowmick,Neil, Cedars-Sinai Medical Center Los Angeles United States, prostate...
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Our studies evaluate how recurrent dehydration can cause chronic kidney disease, an important question for the military and public. We hypothesize, based on preliminary data, that dehydration associated renal injury results from hyperosmolarity induced activation of renal aldose reductase-fructokinase. We made excellent progress this last year. First, we now have the floxed KHK KO mouse and have generated successful litters so we can proceed with selective renal knockout of fructokinase in...
Topics: DTIC Archive, Johnson,Richard J, Regents of the University of Colorado Aurora United States,...
The purpose of the study is to see if an eight-week course of forty low-pressure HBOT's can significantly improve symptoms and cognitive function in military veterans and civilians with mild TBI/PPCS. The proposed design is a randomized controlled (non-treatment, non-sham) single-arm crossover single-blind study. The scope of the project is to recruit, enroll, test, treat, re-test and follow-up on 50 subjects at Louisiana State University, New Orleans in 23 months and another 50 subjects at...
Topics: DTIC Archive, Harch,Paul G, Louisiana State University Health Sciences Center-N.O. New Orleans...
Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder where patients, over the course of decades, develop large fluid filled cysts that damage the normal kidney tissue and can lead ultimately to kidney failure that necessitates transplantation or dialysis. There are currently no FDA-approved medications for this condition. Recent research reveals that the formation of cysts is due in part both to inappropriate cell growth, fluid secretion, and dysregulation of...
Topics: DTIC Archive, Caplan,Michael J, Yale University New Haven United States, kidney diseases, Cysts,...
The goal of this contract is to develop an implantable pudendal nerve stimulator to obtain the FDA approval for a future clinical trial to restore bladder function in human after SCI. During the first year of the contract, we have achieved the following:1. In Cube Labs (subcontractor) has developed the pre-application material for FDA approval of Humanitarian Use Designation (HUD) of the device.2. In Cube labs has designed and manufactured the first prototype of the stimulator, including both...
Topics: DTIC Archive, Tai,Changfeng, University of Pittsburgh Pittsburgh United States, wounds and...
During the inevitable progression to castration resistant stage, prostate cancer cells acquire resistance to anti-androgens.Paradoxically, despite the prolonged AR antagonist treatment, expression of AR is not abated in CRPCs, signifying AR as the Achilles heel to achieve realistic therapeutic benefit in CRPC patients. Recently, it has been reported that prostate cancer cells positive for AR-signaling and CRPC xenograft tumors display exquisite sensitivity to JQ1, a BET bromodomain inhibitor....
Topics: DTIC Archive, Mahajan,Kiran, H. Lee Moffitt Cancer Center and Research Tampa United States,...
Enzalutamide has clinical activity in breast cancer as a single agent and in combination with exemestane. Activity is seen in both triple negative AR BC and also ER AR BC. Clinical data in Her2 AR BC is too immature to make conclusions. The proposed clinical trials for Years 3-5 appear to be justified based on clinical activity and the current preclinical data.
Topics: DTIC Archive, Elias,Anthony, University of Colorado Denver Aurora United States, breast cancer,...
Defense Technical Information Archive
by Defense Technical Information Center
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Breast cancer develops from breast mucosa and breast mucosa has intact immune system to maintain epithelial integrity. In this study our goal was to study the immune subsets associated with breast mucosa and develop the strategies to populate mucosa with immune effectors in order to prevent breast cancer. Data obtained from our studies suggest that T cells constitute the majority of immune cells in breast mucosa and this includes conventional CD4 T cells, CD8+ T cells and significant fraction...
Topics: DTIC Archive, Knutson,Keith L, Mayo Clinic Jacksonville Jacksonville United States, breast cancer,...
The goal of this proposal was to determine whether cell fusion between tumor cells and hematopoietic cells is the precipitating event for breast cancer metastasis and whether viral fusion proteins enable or catalyze this event. Our results suggest therapeutic strategies to disrupt or inhibit cell fusion could reduce tumor heterogeneity and limit the formation of metastases. In support of this statement we demonstrated the following in the course of the funded award. First, we found mesenchymal...
Topics: DTIC Archive, Ogle,Brenda, University of Minnesota-Twin Cities Minneapolis United States, breast...
The purpose is to evaluate the safety and efficacy of 200 U OnaBoNT-A injected into the detrusor versus oral oxybutynin for the treatment of urinary incontinence (UI) caused by neurogenic detrusor overactivity (NDO) in spinal cord injured volunteers; and (2) To determine the potential role of urine biomarkers as patient selection and surrogate endpoints of treatment outcome predictors. Thirty-six patients will be randomized to two treatment groups. The first patient was enrolled to the study at...
Topics: DTIC Archive, Smith,Christopher P, Baylor College of Medicine Houston United States, proteins,...
The purpose of this study is to demonstrate the effectiveness of a PBPT intervention for the prevention of disability in ADSM who sustain an MSI during deployment in support of combat operations on a carrier. This includes testing the feasibility of the implementation and documenting psychological risk factors aboard two carriers. We have successfully completed the training of the control carrier.
Topics: DTIC Archive, Weiser-Horwitz,Sherri, New York University New York United States, Physical fitness,...
This study is a follow-on to prior DOD funded work Efficacy of a Driving Intervention Program on Safe Community Mobility for Combat Veterans. Funding for the Effectiveness (current) study was activated in October 2015 and appointed team members include CO-Is (Classen, Levy, Marsiske and Brumback) and Graduate Research Assistant (Yarney).To date our primary focus has been Specific Aim 1: Enhance the OT-DI with development of targeted simulator drives addressing CV driving triggers and assess...
Topics: DTIC Archive, Winter,Sandra, University of Florida Gainesville United States, rehabilitation,...
Introduction: The internal anatomy of the mesial root of the mandibular first and second molar is highly complex. Literature supports a variety of canal presentations ranging from 1 canal to multiple canals. The presence of a third canal called the middle mesial canal (MM) is well documented. The MM canal can go undetected unless the clinician is careful to identify it. Missing this canal can contribute to a sequelae of persistent disease that may require the retreatment of the tooth or...
Topics: DTIC Archive, Torres,Christopher O, Uniformed Services University of the Health Sciences Bethesda...
Purpose: Platinum-based chemotherapy has been the mainstay of ovarian cancer therapy for the past three decades. More recently,poly(ADP-ribose) polymerase (PARP) inhibitors have emerged as promising agents for the treatment of ovarian cancer. However,similar to platinum, all patients eventually demonstrate tumor progression while being treated with PARP inhibitor therapy, and drug resistance is a major clinical hurdle. The BRCA1 protein is involved in homologous recombination (HR) DNA repair,...
Topics: DTIC Archive, Johnson,Neil, Institute for Cancer Research Philadelphia United States, ovarian...
Defense Technical Information Archive
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Follistatin is a possible anabolic treatment for denervation atrophy induced muscle weakness following prolonged denervation.Adenovirus delivery of Recombinant FS-288 DNA isoform does not induce hypertrophy in normal rodent gastrocnemius muscle. The efficacy of Adenoassociated virus delivery of FS-288 DNA or direct delivery of recombinant FS-288 protein is currently not known.
Topics: DTIC Archive, Isaacs,Jonathan, Virginia Commonwealth University Richmond United States, muscular...
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Autism spectrum disorders (ASDs) are disorders that affect as many 1 in 88 children. Without intensive treatment, the long-term outcomes for children with an ASD remain bleak and are associated with a high divorce rate among parents. Interventions based on applied behavior analysis are well documented, but unfortunately these services are often not available to military-dependent children because of the lack of appropriately training individuals. This project will demonstrate how web-based...
Topics: DTIC Archive, Fisher, Wayne W, University of Nebraska Medical Center Omaha United States, clinical...
Very low birth weight premature neonates undergo phlebotomy procedures on admission to the neonatal intensive care unit that require 10 of their total blood volume. Increasing their likelihood of anemia requiring packed red blood cell transfusion. A strategy to decrease the risk of anemia includes use of umbilical cord blood for admission lab tests. Our objective is to compare the use of umbilical cord vs. infant blood as a strategy to decrease the risk of anemia requiring PRBC transfusion in...
Topics: DTIC Archive, Prescott,Alicia, San Antonio Military Medical Center Fort Sam Houston United States,...
Defense Technical Information Archive
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Dystonia is a disabling and incurable neurological disorder characterized by twisting movements that cause significant disability. Some forms of dystonia are caused by genetic mutations and, therefore, passed on from generation to generation. The most common form of early onset genetic dystonia is a disease known as DYT1, in which children around age ten develop dystonia, usually in a leg or arm, and over 2 or 3 years spreads to affect all body parts causing substantial disability. There is no...
Topics: DTIC Archive, Gonzalez-Alegre,Pedro, The Children's Hospital of Philadelphia Philadelphia United...
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We hypothesize that tamoxifen, trifluoperazine or combined tamoxifen-trifluoperazine therapy will effectively treat established neurofibromas and MPNSTs and prolong survival. We also hypothesize that prophylactic treatment with these drugs will prevent neurofibroma and MPNST pathogenesis. To test these hypotheses, we will: 1) determine whether tamoxifen, trifluoperazine or tamoxifen-trifluoperazine therapy effectively inhibits tumor cell proliferation and survival in established neurofibromas...
Topics: DTIC Archive, Carroll,Steven L, Medical University of South Carolina Charleston United States, cell...
Defense Technical Information Archive
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The aim of our research is to generate and characterize mouse models of human hereditary pancreatitis that develop pancreatitis spontaneously or exhibit increased sensitivity to experimentally induced pancreatitis. Such models are desperately needed to study in vivo the mechanistic aspects of the trypsin-dependent pathway in pancreatitis and to begin testing therapeutic and preventive approaches. Mutations in the digestive enzyme trypsinogen cause hereditary pancreatitis in humans. Previous...
Topics: DTIC Archive, Sahin-Toth,Miklos, Trustees of Boston University Boston United States, pancreatitis,...
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Technologies such as transcriptional profiling, genome sequencing, epigenetic, proteomic or metabolomic profiling have resulted in large sets of genome wide data. However, most of these datasets are of correlative. Functional and phenotypic annotation of the genome is thus a key challenge for a fundamental understanding of physiology and disease pathogenesis. We combine genetic model organisms and repairable mutagenesis with in vivo mouse genetics and human cohort studies to functionally...
Topics: DTIC Archive, Penninger,Josef, IMBA Institut fuer Molekulare Biotechnologie GmbH Vienna Austria,...
This project has made very good progress. We have now unveiled an even larger role for defective apoptosis in the emergence of resistance. We have been very successful in our ability to generate cell lines derived from patient biopsies both before treatment and at the time of resistance. We are now using these patient-derived cell lines to assess BIM levels and apoptotic response to next-generation inhibitors.
Topics: DTIC Archive, Engelman,Jeffrey, Massachusetts General Hospital Boston United States, apoptosis,...
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In this project, we have proposed to design and test an innovative nanotherapeutic system to attack prostate cancer occurred in skeletal tissue. The proposed targeted, bio-responsive nanotherapeutics are based on peptide-functionalized diblock copolymers of poly(ethylene glycol) and poly(trimethenecarbonate) (PEG-PTMC) as the drug carrier, by using docetaxel as the therapeutic agent. During the past funding period, copolymers with predetermined terminal functionality, molecular weights and...
Topics: DTIC Archive, Wang,Xuli, University of Utah Salt Lake City United States, prostate cancer,...
Defense Technical Information Archive
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This report describes continued work on the award Neurocognitive Effects of Radiotherapy, which examines the neurocognitive and imaging impact of proton therapy for patients will low grade glioma and base of skull meningioma. A total of 58 patients have been enrolled. All cohort 1 and 2 patients have completed a 4-5 hour neurocognitive testing assessment at baseline by Dr. Carol Armstrong. In addition, cohort patients have completed a 1 hour standard MRI as well as additional testing including...
Topics: DTIC Archive, Armstrong,Carol, Trustees of the University of Pennsylvania Philadelphia United...
The purpose of this study is to evaluate the efficacy of a telephone-delivered cognitive behavioral treatment (T-CBT) in Veterans with a history of traumatic brain injury (TBI) for the treatment of chronic pain in a randomized controlled trial (RCT). Specifically, the RCT will examine the immediate (at the end of treatment) and long-term (6-months from randomization) efficacy of T-CBT on average pain intensity (primary outcome), and pain interference, sleep, depression, global impression of...
Topics: DTIC Archive, Hoffman,Jeanne M, University of Washington Seattle United States, brain injuries,...
This research project focused on genetic analysis of a rare subset of prostate cancer cases: men presenting with metastatic prostate cancer at a young age (before age 60 years). Whole exome sequencing identified a panel of germline variants that have biological as well as genetic evidence suggesting that they may be related to inherited susceptibility of early-onset aggressive prostate cancer. Comprehensive tumor genome and/or transcriptome sequencing of tumors from these patients identified an...
Topics: DTIC Archive, Cooney,Kathleen A, Regents of the University of Michigan Ann Arbor United States,...
An important objective of the Project Solicitation for Agent Therapeutics (Task Area 2.H) was to determine the effectiveness of current medical countermeasures against the acute toxicity of nerve agents. This project evaluated the efficacy of skin decontamination products and barrier skin creams. Doctrine described the use of Skin Exposure Reduction Paste Against Chemical Warfare Agents (SERPACWA)as a barrier skin cream and the M291 Skin Decontamination Kit (SDK), 0.5% hypochlorite solution...
Topics: DTIC Archive, Braue,Ernest Jr H, U.S. Army Medical Research Institute of Chemical Defense Aberdeen...
Why GAO Did This Study.DOD reports that between 2005 and 2013, the number of individuals who received mental health care through DODs MHS grew by 32 percent. MHS mental health care is provided free to active duty servicemembers. Reservists and DOD civilians are eligible for MHS care under certain circumstances.The National Defense AuthorizationAct for Fiscal Year 2015 contains a provision for GAO to assess the availability and accessibility of mental health care in DODs MHS for military...
Topics: DTIC Archive, Williamson,Randall B, U.S. Government Accountability Office Washington United States,...