nasa scientific and technical aerospace reports phần 4 potx

2004; 38 pp.; In English; Original contains color illustrations Report No.s: AD-A432228; No Copyright; Avail: Defense Technical Information Center DTIC The purpose of this research is to

Trang 2

on fresh and frozen serum and differing HIV sub- types have been conducted in both the research and field environments.Testing has been compared to reference technology for calculation of operating characteristics Conclusion: Rapid HIV-1testing technology is an evolving field subject to market demands Several tests exist that support warfighter use in the field.However, these tests should still be utilized in the context of the medical risk decision making process.

DTIC

Blood; Military Operations; Serums; Viruses

20050173139 Naval Medical Research Inst., Portsmouth, VA USA

Improving Management of Pediatric Patients with Attention- Deficit/ Hyperactivity Disorder at Naval Medical Center Portsmouth

Caron, Roger; Apr 2004; 38 pp.; In English; Original contains color illustrations

Report No.(s): AD-A432228; No Copyright; Avail: Defense Technical Information Center (DTIC)

The purpose of this research is to determine if the selection of a primary care or psychiatrist provider, is significantlydifferent between direct care and network providers, given similar diagnosis of attention-deficit hyperactivity disorder(ADHD) in children between the age of 5 and 17 The Chi-square statistical analysis is used to determine the extent of therelationship Results of the test revealed a statistical significance given a Chi-square value of 365.84, 90, 1 and a critical value

of 6.63 The explanation for beneficiary selection of psychiatric specialists vice their primary care provider was found to bedependant on current rules not requiring a referral for mental health care coupled with no out of pocket expense for care Theapplication of best business practices is explored to reduce this trend The implementation of ADHD clinical path guidelines,marketing strategies and utilization of current pharmacy programs are recommended

DTIC

Medical Services; Mental Health; Military Operations; Patients

20050173140 Duke Univ., Durham, NC USA

Analysis of the Link Between Acquired Expression of a Master Switch Gene of Osteoblast Differentiation by Breast Cancer and Bone Metastasis

Wang, Xiao-Fan; Aug 2004; 10 pp.; In English

Contract(s)/Grant(s): DAMD17-03-1-0600

Report No.(s): AD-A432229; No Copyright; Avail: CASI;A02, Hardcopy

Bone metastasis of breast cancer is a major cause of death among breast cancer patients However, we still know relativelylittle about why many breast cancers metastasize to the bone To develop better treatments of bone -metastasis of breast cancer,

we need to understand how breast cancer cells acquire the abilities to move to the bone, survive in the new environment, andflourish as metastatic tumors We postulate that one potential mechanism by which breast cancer cells may acquire suchabilities is their acquired expression of bone specific proteins that are known to be involved in mediating the activities of thebone-forming cells in the bone tissue, the - osteoblasts In this study, we attempted to address the critical question of whetherthe expression of a master gene for the development of bone-forming osteoblast cells, CBFAl, by the breast cancer cells leads

to bone metastasis in an established animal model system To do this, we manipulated the expression of this gene in establishedhuman breast cancer cell lines and planned to -monitor the ability of those cancer cells to grow in the bone as metastases Apositive finding from such studies will pave the way for the development of potential therapeutic agents for the treatment ofthis horrifying disease

DTIC

Bones; Breast; Cancer; Mammary Glands; Metastasis; Osteoblasts; Switches

20050173141 Naval Postgraduate School, Monterey, CA USA

Using Web-Based Interactive Multimedia to Supplement Traditional Teaching Methods: A Pilot Program for Medical Training of Non-Medical Personnel

Gellman, Gregg W.; Mar 2005; 166 pp.; In English; Original contains color illustrations

This thesis proposes that it is possible to create an adjunct to traditional instructor-led training that will reduce trainingtime and costs and at the same time improve performance using commercial off-the shelf (COTS) software Motivated by thelessons learned following the attack on the USS Cole on October 12, 2000 in which 17 sailors were killed and 42 werewounded, we created a simulator using readily available software in minimal time with zero funding and tested it against smallsample sizes of eventual recipients of the training The simulator, as part of a blended learning solution, was shown to be as

Trang 3

effective as traditional instructor-based learning but was conceived at a fraction of the cost and with a significant reduction

in total training time Both of these factors are increasingly being valued in today’s reality of increased operational tempo andreduced resources

DTIC

Computer Programs; Education; Medical Personnel; Medical Services; Multimedia; Pilot Training

A Functional Genomics Approach to Identify Novel Breast Cancer Gene Targets in Yeast

Bennett, Craig; May 2004; 39 pp.; In English

We are using the yeast Saccharomyces cerevisiae to identify new cancer gene targets that interact with the tumorsuppressor Brcal Expression of Ercal in diploid WT yeast leads to prolonged Gi arrest and lethality We identified from acollection of ionizing radiation (IR) -sensitive yeast deletion strains or from a pool of 4%46 genetically tagged deletion strains,

34 that rescue Brcal-induced lethality Two IR resistance genes that rescue Brcal-induced lethality are the transcription factorsCCR4 and DHHl These are checkpoint genes required for cell cycle progression in Gl and S phases following DNA damage.Consistent with a role in radiation resistance, Dhhlp and its highly conserved human ortholog DDX6 were found to physicallyinteract with Brcal in yeast and human cells Another transcription factor (YAF9) was IR sensitive and rescued Brcal-inducedlethality when deleted This deletion strain and 19 others were subsequently isolated from the deletion strain pool Most ofthese deletions (75%) were IR sensitive and hypersensitive to the toxin zymocin which appears to induce DSB damage byinhibiting transcription Furthermore, most (85%) of these genes are highly conserved suggesting that the hunan orthologs mayinteract with Brcal to maintain genomic stability and suppress the onset of breast cancer

DTIC

Breast; Cancer; Genome; Mammary Glands; Targets; Yeast

20050173143 Ohio State Univ., Columbus, OH USA

Development of Dual Acting Inhibitors for Breast Cancer

Li, Pui-Kai; Nov 2004; 17 pp.; In English

Purpose: To design dual acting inhibitors that can block the enzyme estrone sulfatase and act as antiestrogens Scope: Thedesign and%synthesis of 30 dual inhibitors are proposed The inhibitors contain 4 different structural core The synthesizedinhibitors will be tested on their ability to inhibit the enzyme estrone sulfatase and also their abilities to inhibit the growth ofbreast cancer cells stimulated by estrone suffate In addition, selected inhibitors will be tested in vivo using NMU-inducedmammary tumors inrats: Major findings: All thirty of the proposed inhibitors have been synthesized The inhibitors have beentested for their ability to inhibit estrone sulfatase activity of rat liver microsomes at 20 %M concentrations and in the presence

of 20 %M of substrate estrone sulfate All the inhibitors tested so far are more potent thanour lead compound Tamoxifensulfamate Raloxifene sulfamate (inhibitor 30) is still the most potent compound among the 30 inhibitors we have synthesized

It inhibits more than 95% of the sulfatase activity at 20 %M concentration It is by far the most potent dual inhibitor we haveever obtained We have selected inhibitor 30 as one of the compounds for in vivo study using NMU-induced mammary tumors

in rats We have synthesized 4 grims of the compound needed for the study Unfortunately, ten percent of compound 30degraded unexpectedly Which delay ourin vivo studies The proposed in vivo study is delayed awaiting the synthesis 9f morecompound 30

DTIC

Breast; Cancer; Inhibitors; Mammary Glands

Agent-Based Simulation of Disease Spread Aboard Ship

Gutierrez, Louis M.; Mar 2005; 65 pp.; In English; Original contains color illustrations

Extreme examples like the Spanish Flu pandemic of 1918 make clear the devastating impact that communicable diseasescan have on military readiness It is highly desirable to have models and tools that can be used to evaluate the course of adisease over time These tools can help assess the effectiveness of strategies employed to contain the outbreak such as

Trang 4

constraining movement, wearing protective gloves or masks, closing high traffic areas, etc Armed with these tools, a medicalpractitioner can better assess the right course of action in a time critical situation The primary difficulty with creating modelsand simulations for this purpose is that disease spread depends upon the details of human behavior and environmentalvariables which are not accounted for in current mathematical models The likelihood that a particular individual will catch

a given disease depends upon such specifics as where he works, whom he interacts with, where he sleeps, what he eats, hishabits of personal hygiene, etc It is hypothesized that a software disease simulation can combine agents that mimic humanbehavior, a ship specific environment, and disease specific attributes to more accurately model the spread of disease aboardship than a mathematical model

DTIC

Computerized Simulation; Diseases; Infectious Diseases; Maintainability; Military Operations; Ships; Simulation

20050173148 Texas Univ., Arlington, TX USA

Non-Invasive Monitoring of Breast Tumor Oxygenation: A Key to Tumor Therapy Planning and Tumor Prognosis

Liu, Hanli; Sep 2004; 202 pp.; In English

The overall goal of this research project is to develop and evaluate a new approach to monitoring of oxygenatedhemoglobin concentration (HbO2) of breast tumors under respiratory interventions using near infrared (NIR) spectroscopy andimaging techniques The aims have included (1) to evaluate a single-channel, dual wavelength, NIR, frequency-domainoximeter and the algorithms for obtaining tumor HbO2 against tumor PO2 measured by 19F magnetic resonance imaging(MRI), (2) to modify the single-channel system into a 3-channel NIR system, (3) to investigate heterogeneity of HbO2 inbreast tumors using the 3-channel NIR system, and (4) to study the influence of three interventions on HbO2 and PO2 of thebreast tumors We have accomplished all of the proposed aims and compared the optical method with concurrentmeasurements of tumor oxygen tension using oxygen needle electrodes, fiber optic needle systems (FOXY), and 19F MRI.Overall, we conclude that NIR techniques could be a useful non-invasive monitoring tool for breast tumor oxygenation, which

is a key to breast tumor therapy planning and tumor prognosis Furthermore, the need for NIR imaging is obvious and is ourcurrent research development in order to fully characterize static and dynamic heterogeneity of breast tumor vasculature undertherapeutic interventions

DTIC

Breast; Cancer; Mammary Glands; Prognosis; Therapy; Tumors

20050173153 Army Medical Research Inst of Infectious Diseases, Fort Detrick, MD USA

Quorum Sensing: A Transcriptional Regulatory System Involved in the Pathogenicity of Burkholderia mallei

Ulrich, Ricky L.; DeShazer, David; Hines, Harry B.; Jeddeloh, Jeffrey A.; Nov 2004; 9 pp.; In English; Original containscolor illustrations

Contract(s)/Grant(s): Proj-02-4-5X-026

Numerous gram-negative bacterial pathogens regulate virulence factor expression by using a cell density mechanismtermed quorum sensing (QS) An in silico analysis of the Burkholderia mallei ATCC 23344 genome revealed that it encodes

at least two luxI and four luxR homologues Using mass spectrometry, we showed that wild-type B mallei produces thesignaling molecules N-octanoyl-homoserine lactone and N-decanoyl-homoserine lactone To determine if QS is involved inthe virulence of B mallei, we generated mutations in each putative luxIR homologue and tested the pathogenicities of thederivative strains in aerosol BALB/c mouse and intraperitoneal hamster models Disruption of the B mallei QS alleles,especially in RJ16 (bmaII) and RJ17 (bmaI3), which are luxI mutants, significantly reduced virulence, as indicated by thesurvival of mice who were aerosolized with 10 to the 4th power CFU (10 50% lethal doses) For the B mallei transcriptionalregulator mutants (luxR homologues), mutation of the bmaR5 allele resulted in the most pronounced decrease in virulence,with 100% of the challenged animals surviving a dose of 10 LD50s

DTIC

Detection; Mass Spectroscopy; Pathogenesis; Regulations; Virulence

20050173155 Tripler Army Medical Center, Honolulu, HI USA

Cost-Benefit Analysis of Radiation Therapy Services at Tripler Army Medical Center

Diehl, Diane S.; Sep 2004; 71 pp.; In English; Original contains color illustrations

Trang 5

The purpose of this analysis was to examine the costs and benefits associated with continuance of ‘in-house’ radiationtherapy services to eligible beneficiaries at Tripler Army Medical Center (TAMC), as opposed to purchasing services Indetermining the optimal solution for TAMC, three models were developed and used to project, for FY04 through FY10, afinancial analysis using historical data The analysis indicated purchasing radiation therapy services, i.e., outsourcing this carewould produce a cost avoidance of $442,683 to $604, 619, depending upon model comparison However, the financial dataalone is insufficient to determine the optimal solution Qualitative factors were analyzed using a relative values decisionmatrix Evaluation criteria consisted of cost, access, perceived quality, measurable quality, and political views These criteriawere ranked and weighted A threats, opportunities, weaknesses, and strengths matrix was then used to establish the strategicdirection Based on the results of this analysis, it is recommended that TAMC continue to provide radiation therapy servicesin-house and enhance those services through purchase of intensity-modulated radiation therapy technology.

DTIC

Chemotherapy; Cost Analysis; Cost Effectiveness; Medical Services; Military Operations; Radiation Therapy

20050173170 Great Plains Regional Medical Command, Fort Sam Houston, TX USA

A Feasibility Study on the Implementation of Teleophthalmology in the Medical Treatment Facilities in the Great Plains Regional Medical Command

Dixon, Margaret L.; Jun 2004; 99 pp.; In English; Original contains color illustrations

With the ever increasing costs of health care today finding, testing, and, if found workable, utilizing a new technology

is an absolute must Teleophthalmology is just such a technology This service will greatly benefit the present and growingdiabetic population One of the major complications of diabetes is diabetic retinopathy, which eventually causes blindness Theeffects of diabetic retinopathy can be limited if early and effective treatment is provided The key to early intervention is anannual eye exam The compliance rate for annual eye exams for Great Plains Regional Medical Command is less than the 90%required to meet HEDIS as well as our own Clinical Practice Guideline metric Teleophthalmology is a way to meet the needs

of the patient for an eye exam without a second visit to the hospital Utilizing a digital ophthalmic camera allows the patient’spupils to be dilated, the films obtained and sent for review by an ophthalmologist during their routine primary care visit Thisdecreases the hassle factor for the patient, it frees up ophthalmology clinic visits held for routine diabetic eye exams, and bestutilizes the limited number of ophthalmology providers available in the region

DTIC

Eye (Anatomy); Feasibility; Great Plains Corridor (North America); Ophthalmology

20050173175 RAND Corp., Santa Monica, CA USA

Determinants of Dispensing Location in the TRICARE Senior Pharmacy Program

Malkin, Jesse D.; Joyce, Geoffrey; Pace, Jennifer; Croghan, Thomas; Jan 2005; 94 pp.; In English

Contract(s)/Grant(s): DASW01-C-01-0004

The MHS serves approximately 8.6 million eligible beneficiaries, including active-duty military personnel and theirfamily members (dependents), retired military personnel and their dependents, and surviving dependents of deceased militarypersonnel TRICARE, the program that administers health care for the DoD, includes a pharmacy benefit that providescoverage for virtually all U.S Food and Drug Administration (FDA) approved prescription medications Prior to fiscal year(FY) 2001, elderly military retirees and their dependents who wished to use their military benefits to fill a prescription could

do so only at a MTF outpatient pharmacy; However, some drugs that were frequently prescribed by civilian providers werenot always available at MTFs because of formulary restrictions As of FY 2001, DoD introduced a new program for elderlymilitary retirees and their dependents, entitled TRICARE Senior Rx (TSRx) TSRx beneficiaries can now fill theirprescriptions at any of four points of service: (1) outpatient pharmacies at MTFs; (2) the TRICARE Mail Order Pharmacy(TMOP), 3 currently administered by Express Scripts Inc.; (3) retail pharmacies contracted by regional TRICARE contractors(referred to as ‘network’ pharmacies); and (4) non-network retail pharmacies The TMOP dispenses drugs for chronicconditions Although it cannot dispense a few drugs, such as atorvastatin, without proof of medical necessity theoverwhelming majority of drugs for chronic conditions are available Retail pharmacies have completely open formularies:TRICARE reimburses them for all prescriptions except those specifically excluded from TRICARE coverage

DTIC

Dispensers; Health; Medical Services; Military Operations; Pharmacology; Position (Location)

Trang 6

20050173176 RAND Corp., Santa Monica, CA USA

Pharmacy Use and Costs in Employer-Provided Health Plans Insights for TRICARE Benefit Design from the Private Sector

Joyce, Geoggrey; Malkin, Jesse D.; Pace, Jennifer; Jan 2005; 94 pp.; In English

Contract(s)/Grant(s): DASW01-C-01-0004

The military health system (MHS) has approximately 8.6 million eligible beneficiaries, including active-duty militarypersonnel and their family members, retired military personnel and their family members, and surviving family members ofdeceased military personnel In 2002, the Department of Defense (DoD) spent about $3 billion on outpatient pharmacybenefits Like the private health care sector, the MHS has experienced a rapid growth in pharmaceutical expenditures At therequest of DoD, the RAND Corporation has undertaken two studies designed to help DoD shape their pharmacy benefit policy

to control costs The U.S Congress has identified the TRICARE pharmacy benefit as an area for reform Section 701 of theNational Defense Authorization Act for Fiscal Year 2000 requires the Secretary of Defense to establish an effective, efficient,and integrated pharmacy benefits program As part of a program redesign effort, which will result in the establishment of aUniform Formulary (UF), the DoD is considering moving from a two-tiered copayment system to a three-tiered copaymentsystem, which will increase the copayment for some classes and brands of medications It is hoped that this move will giveproviders (acting in the interest of their patients) an incentive to prescribe lower-tier, less-costly options To assist the DoD

in assessing the potential implications of this policy change, RAND used an existing data resource to examine howbeneficiaries with private drug coverage responded to similar changes in pharmacy benefits The findings from this analysis,presented in this report, can inform the DoD of the potential costs and benefits of adopting the proposed Uniform Formulary.DTIC

Costs; Health; Medical Services; Military Operations; Pharmacology

20050173208 Blanchfield Army Community Hospital, Fort Campbell, KY USA

Investing in the Future by Learning from the Past: Developing a Survey Tool to Gather Feedback from Deployed Army Forward Surgical Team

Morton, Richard; Jun 2004; 64 pp.; In English; Original contains color illustrations

The purpose of this Graduate Management Project (GMP) was to develop a validated survey instrument to gather crucialfeedback from deployed Forward Surgical Teams (EST) for use by the Army Medical Department Center and School(AMEDD C&S) in the developmental evolution of the Program of Instruction (POI) for the Army Trauma Training Center(ATTC), currently operating out of Ryder Trauma Center, Miami, Florida Three critical processes or phases were used toassure validity in the initial design of this tool After a thorough literature review, an initial template was developed withassistance from the Executive Officer (XO) and another instructor assisted in staffing this tool through the ATTC The secondphase was to have the Survey Administrator, AMEDD C&S, automate and modify the survey to comply with Center andSchool training feedback objectives and the Army Surgeon General’s Balanced Scorecard Finally, the tool went through asecond audit conducted by the ATTC and was piloted for content through the 801st FST at Fort Campbell The objective ofdeveloping a solid instrument for the ATTC was completed during the course of this project Ultimately, utilizing this tool togather feedback will be essential to evaluate the Army’s current trauma training program and enhancing the quality of care

we deliver on the battlefield

DTIC

Deployment; Feedback; Learning; Surgery; Surveys

20050173214 Delaware Univ., Newark, DE USA

Mucin (MUC1) Expression and Function in Prostate Cancer Cells

Carson, Daniel D.; Mar 2004; 24 pp.; In English

Mucin glycoproteins are highly expressed by many tumors, reduce normal cell-cell and cell-extracellular matrix adhesionand protect cancer cells from attack by the immune system Mucin expression not only increases, but also changes from arestricted pattern of apical expression to a general distribution over the entire cell surface In this regard, conversion of prostateepithelium from a highly-organized, growth-controlled phenotype to a highly proliferative, metastatic phenotype is associatedwith loss of cell polarity Very few studies been performed on mucin expression by prostate cancer cells MUC1 is a largemolecular weight, type I transmembrane mucin glycoprotein expressed by normal and malignant prostate epithelium High

Trang 7

level cell surface expression, reported immunosupressive activities of its released ectodomain, and antiadhesive properties allcontribute to this mucin’s ability to protect and promote tumor cell growth and survival Recent observations using humanbreast cancer cell lines indicate that MUC1 can associate with the intracellular signal transducing molecules, beta-catenin andGRB-2 Recent studies from the PI’s lab demonstrate that cytokines, including interferon-gamma, markedly stimulate MUC1gene expression Primary prostate tumors are often found in the vicinity of cytokine producing cells, and commonlymetastasize to bone marrow, a rich source of these same cytokines.

DTIC

Cancer; Prostate Gland; Proteins

20050173216 University of Southern California, Los Angeles, CA USA

Development of Quantum Dot Probes for Near-Infrared Fluorescence Imaging of Breast Cancer Angiogenesis

Chen, Xiaoyuan; Sep 2004; 23 pp.; In English

The overall objective of this proposal is to develop cyclic RGD peptide conjugated biocompatible quantum dotnanoparticles for near-infrared fluorescence imaging of breast cancer angiogenesis The two hypotheses to be tested are that:1) the integrin alpha(v)beta(3) antagonist, when conjugated with semiconductor nanocrystals, will not change the fluorescentproperties of the QDs significantly; and 2) the QD-based breast cancer angiogenesis probes are specific enough to recognizethe integrin receptor and bright enough for effective detection in preclinical animal models Specific Aim 1: to preparewater-soluble QD-RGD conjugates and characterize the probes in vitro Specific Aim 2: to assess the tumor targeting efficacy

of QD-RGD in breast cancer model Major Findings: Although biocompatible quantum dots in theory is superior to organicdyes for long-term, multi-target and highly sensitive imaging, however, the current surface coating techniques do not offerenough stability of QDs in biological medium On the other hand, NIR fluorescent dyes labeled RGD peptides demonstratedhighly sensitive and semi-quantitative NIR fluorescence images for tumor detection in preclinical xenograft models Thisnon-invasive optical imaging approach provides the opportunity for rapid and cost-effective studies before more costlyradionuclide-based imaging studies

DTIC

Angiogenesis; Breast; Cancer; Fluorescence; Images; Imaging Techniques; Mammary Glands; Quantum Dots

20050173217 New South Wales Univ., Sydney, Australia

The Role of p53 Mutations in Metastasis of Prostate Cancer to Bone

Russell, Pamela J.; Blair, Julie M.; Kingsley, Elizabeth A.; Szymanska, Barbara; Perryman, Lara; Jackson, Paul; Dec 2004;

89 pp.; In English

The spread of prostate cancer (CaP) to bone causes morbidity and death, yet interactions between CaP cells and bone arepoorly understood To test if specific mutations of the tumor suppressor gene, p53, that occur in CaP cause disease progression,

we generated cell lines from the human LNCaP cell line that stably express normal or mutant p53 Purpose: To test whetherp53 mutations affect establishment/growth of experimentally-induced CaP in the bone Score: LNCaP cell lines were tested

in tissue culture for factors that alter normal bone remodeling and angiogenesis and were implanted in immuno-incompetentmice to analyze their ability to form tumors and to spread to the bone Results/ Progress: p53-mutant CaP cells modulatedosteoclastogenesis and affected osteoblast proliferation; different p53 mutations showed differentiation stage-dependenteffects Osteoblasts also stimulated the growth of p53 mutant CaP cells, suggesting that osteoblast-CaP interactions lead to newbone formation and allow CaP to establish in bone When implanted in mice, some p53 mutant CaP cells inhibitedangiogenesis, and were cytotoxic to bone marrow derived endothelial cells in vitro We aim to identify the moleculesresponsible for these effects Significance: Further studies will explain how specific mutations of p53 found in patients impact

on progression, and could allow development of new therapeutic strategies

DTIC

Bones; Cancer; Metastasis; Mutations; Prostate Gland; Tissue Culturing

20050173221 Dana Farber Cancer Inst., Boston, MA USA

Functional Study of the Human BRCA2 Tumor Suppressor

Xia, Bing; Livingston, David M.; Aug 2004; 11 pp.; In English

Trang 8

My research is focused on the BRCA2 protein, whose mutations have been implicated in the development of breast,ovarian, male breast, prostate, pancreatic cancers and Fanconi anemia It is intended to elucidate some of the biologicalfunctions of BRCA2 and/or regulation of its in vivo function through generation/utilization of new reagents and identification

of new BRCA2 interacting proteins During this second year of grant support, I was able to identify a completely novelprotein, named CLB2 in this study, as a major physiological partner of BRCA2 I discovered that CLB2 is a chromatin boundprotein and is required for BRCA2’s chromatin binding In light of these findings, it is attempting to speculate that disruption

of CLB2 function would lead to significant impairment of BRCA2’s tumor suppressor function realized at least in a large partthrough its DNA recombination/repair activity which presumably requires its docking to the chromatin

DTIC

Breast; Cancer; Mammary Glands; Mutations; Ovaries; Proteins; Suppressors; Tumors

20050173222 California Univ., Irvine, CA USA

Functional Analysis of LIM Domain Proteins and Co-Factors in Breast Cancer

Wang, Ning; Andersen, Bogi; Oct 2004; 28 pp.; In English

We identified a novel transcription factor, LMO4, which is highly expressed in breast epithelial cells during pregnancy when these cells are proliferating and invading the stroma Since previous members of the LIM only (LMO) genefamily are oncogenes, we hypothesized that LMO4 may play roles in mammary gland development and cancer We have nowshown that expression of LMO4 correlates with proliferation, and in transgenic mice we shrewd that dominant-negativeLMO4 inhibits lobuloalveolar development, demonstrating that LMO4 plays roles in proliferation and/or invasion of breastepithelial cells Because these cellular features are associated with breast carcinogenesis and because LMO4 is overexpressed

mid-in a subset of breast cancers, our studies implicate LMO4 as a possible oncogene mid-in breast cancer In addition, we found thatthe LMO4 gene is activated by the Her2/Neu receptor in breast cancer cells, providing further linkage to breast cancer Inbiochemical assays we showed that LMO4 may act by associating with the GATA3 transcription factor, also expressed inmammary epithelial cells We have also created stable breast cancer cell lines in which we can induce expression of LMO4and Clim2 With this method, we have identified several target genes of LMO4, one of which is Bone Morphogenic Protein

7 (BMP-7) , which can affect survival of breast cancer cells by regulating apoptosis In summary, we have defined a role for

a new gene, LMO4, in mammary epithelial cell proliferation in normal development and in breast cancer cells,

DTIC

Breast; Cancer; Functional Analysis; Mammary Glands; Proteins

20050173225 Ontario Cancer Inst., Toronto, Ontario Canada

Analysis of Preneoplasia Associated with Progression to Prostatic Cancer

Yoshimoto, Maisa; Squire, Jeremy; Mar 2005; 101 pp.; In English

PURPOSE: To examine the topographical variation in expression levels of genes associated with prostate cancer, telomeredysfunction and/or chromosomal instability SCOPE: To show that telomere erosion observed in prostatic epithelium mayinvolve DNA damage response/repair pathways at the onset of preneoplasia (HPIN) and cancer in me n MAJ0R FINDINGS:Our working hypothesis is that cells that undergo telomere loss as part of the normal aging process in the prostate are moresusceptible to undergo chromosome end-fusion thus triggering genomic instability Our initial progress showed that loss oftelomere length occurred in preneoplastic HPIN lesions that were located close to small, localized microfoci of newlydiagnosed prostate cancer We have optimized whole genome and RNA amplification techniques and shown that there is highfidelity and reproducibility of dissected amplified PCR product RESULTS: The first phase of gene expression profiling inHPIN, and cancer foci using repair/damage response array has been successfully performed We are developing topographicalmaps of telomere bass, genomic instability and concomitant changes in gene expression SIGNIFICANCE: These results willform the first direct link between telomere-dependent alteration, DNA repair and damage response signaling in prostate cancer.DTIC

Cancer; Chromosomes; Deoxyribonucleic Acid; Prostate Gland

Trang 9

20050173226 Royal Prince Alfred Hospital, Camperdown, Australia

Epigenetic Inheritance of Breast Cancer

Clark, Susan J.; Sep 2004; 20 pp.; In English

Hypermethylation of tumor suppressor genes is only thought to occur in the somatic cell in sporadic tumors However,

we propose that methylation of the promoter of tumor suppressor genes, such as BRCA1, may also occur in the germ-line.Germ-line inheritance of this epigenetic silent state would therefore contribute to familial breast cancer In this study we aimed

to address if methylation of the tumor suppressor gene BRCA1 is inherited through the germ-line and is associated with thehereditary breast cancer We developed a high-throughput sensitive real-time methylation assay that allowed us to screen forBRCA1 methylated DNA We used this assay to screen for BRCA1 methylation from DNA isolated from archival blood andbiopsy samples of women that have a family history of breast cancer but have no defined BRCA1 or BRCA2 mutations.DTIC

Breast; Cancer; Mammary Glands; Methylation

20050173230 Roswell Park Memorial Inst., Buffalo, NY USA

CTL-Tumor Cell Interaction: The Generation of Molecular Probes of Monitoring the HLA-A*0201-HER-2/neu Peptide Complex

Campoli, Michael R.; Mar 2005; 132 pp.; In English

Contract(s)/Grant(s): W81XWH-04-1-0372

The overall goal of this project is to probe the CTL - tumor cell interaction by generating scFv probes that are able torecognize the HLA-A*0201-HER-2/neu369-377 peptide complex In the 12 month period covered by this report, I havesuccessfully generated HLA-A*0201-HER-2/neu369-377 complexes, and have isolated two scFv fragment clones thatrecognize this complex In addition, I have started to analyze the expression levels of antigen processing machinery (APM)components, HLA class I antigens and beta2m in several breast carcinoma cell lines This analysis takes advantage of theavailability of a wide panel of mAb to these antigens that several investigators in our laboratory, including myself, havedeveloped and characterized Collectively, the results we have obtained strongly support our future analysis to correlate theexpression levels of APM components, HLA class I antigens, beta2m and HER-2/neu with the levels of HLA-A*0201-HER-2/neu369-377 complexes on breast carcinoma cells and lesions The information derived from these studies is expected tocontribute to our knowledge of the variables that influence the levels of HLA class I antigen-TAA derived peptide complexexpression on breast carcinoma cells

DTIC

Antigens; Breast; Cancer; Cells (Biology); Mammary Glands; Peptides; Tumors

20050173232 Pittsburgh Univ., Pittsburgh, PA USA

Hormonal Determinants of Mammographic Density

Simpson, Jennifer K.; Modugno, Francesmary; Weissfeld, Joel L.; Kuller, Lewis; Vogel, Victor; Costantino, Joseph P.; Aug.2004; 13 pp.; In English

Hormone Replacement Therapy (HRT) has been shown to increase breast cancer risk as well as to increase breast density.Breast density, a reflection of the histologic composition of the breast, is one factor shown to affect mammographic sensitivityand specificity, and it is predictive of breast cancer risk Thus, the use of HRT, through its effect on breast density, maycompromise the well-established reduction in mortality gained by mammographic screening However, not all women on HRTwill experience an increase in breast density We propose a novel hypothesis to explain in part the individual variability inbreast density seen among women on HRT: differences in breast density are associated with differences in estrogenmetabolism, and this association may be attenuated by individual factors such as body mass index and HRT regimen Our workand the work of others provide compelling evidence to support this hypothesis To date 50 cases and 180 healthypostmenopausal women have been enrolled in this study

DTIC

Breast; Cancer; Determinants; Hormones; Mammary Glands

Trang 10

20050173235 Hawaii Univ., Honolulu, HI USA

Genetic Plymorphisms, Estrogens, and Breast Density

Maskarinec, Gertraud; Jan 2005; 48 pp.; In English

This study investigated the association between genetic polymorphisms in hormone producing and metabolizing enzymesand several markers of breast cancer risk among women of different ethnic background The specific aims were to analyze therelation of breast density and estrogen levels in urine and serum with the presence of variant alleles in CYP17, COMT,CYP1A1, CYP1A2, and CYP1B1, to describe ethnic differences in urinary excretion levels of estrogen, and to explore theassociation of breast density with estrogen levels Mammograms for 328 women were assessed for breast density using acomputer-assisted method The genes were analyzed for polymorphisms using PCR/RFLP methods and estrogens and theirmetabolites were measured by radioimmunoassay We found that women carrying the COMT and CYP1A2 variant alleles hadlower mammographic densities than women carrying the common alleles The CYP1A2 C allele was also significantlyassociated with lower serum estradiol levels and a lower 2OHE1/ 16alpha-OHE1 ratio Total urinary hormone excretion,androgens, 2-OHE1, and the 2/16alpha-OHE1 ratio were significantly lower in women of Asian ancestry than in Caucasians,but breast density was higher among women of Asian ancestry due to their relatively small breast size Estrogens and theirmetabolites measured in the urine of premenopausal women were not associated with mammographic densities However,contrary to the initial hypothesis, the 2-OHE1/16alpha-OHE1 ratio was directly related with mammographic densities.DTIC

Breast; Cancer; Enzymes; Estrogens; Genetics; Mammary Glands; Polymorphism

20050173236 Fox Chase Cancer Center, Philadelphia, PA USA

Hierarchical Nonlinear Mixed Effect Modeling: Defining Post-radiation Therapy Relapse in Prostate Cancer Patients

Hanlon, Alexandra L.; Jul 2004; 107 pp.; In English

The research accomplished and described here validates and extends a model to classify prostate cancer patients according

to disease relapse following definitive radiation therapy The original model was developed within a hierarchical nonlinearmixed effect modeling framework with likelihood based estimation incorporating the EM algorithm The model was testedstatistically using a subset of 35 patients with relatively homogenous tumor and treatment characteristics The researchdescribed in this report successfully applied the methodology to a larger population of men (\g600 patients) representing allstages of disease via the modeling of covariates, including tumor differentiation, stage, and pre-treatment PSA The success

of the modeling was dependent upon a Bayesian framework with Markov chain Monte Carlo methodology for estimatingmixture distribution parameters Poor mixing and slow convergence were encountered and required various re-parameterizations and creative initialization techniques The analysis includes an assessment of predictors of post-nadir rise,

as salvage therapy strategies are often designed around the rate of increase in PSA levels post-nadir, as well as an analysis

of predictors of initial decline and its relationship to outcome The modeling was compared to biochemical classification using

a clinical definition of relapse and also to clinical results as obtained from imaging and/or biopsy

DTIC

Cancer; Nonlinearity; Patients; Prostate Gland; Radiation Therapy

20050173237 California Univ., Berkeley, CA USA

Non-Invasive Imaging of In Vivo Breast Cancer Tissue Utilizing Metabolically Incorporated Unnatural Sugars

Bertozzi, Carolyn R.; Aug 2004; 9 pp.; In English

Cancer cells have long been known to express glycosylation patterns that are different from those found on normal cellsfrom the same tissue Many tumor-specific carbohydrate antigens possess the monosaccharide sialic acid, and as aconsequence, many tumor cells express high levels of sialic acid compared to normal cells Thus, any agent that targets sialicacid specifically could be used for tumor targeting Preliminary work on this project has shown that unnatural sialic acids can

be introduced onto tumor cells metabolically by feeding the cells unnatural analogs of their biosynthetic precursors Theunnatural analogs can include reactive functional groups capable of covalent reaction with exogenous probes For example,

an azide-functionalized analog of Nacetylmannosamine is converted by tumor cells to the corresponding sialic acid, and theazide can be covalently reacted on the cell surface with triarylphosphine probes in vivo The objective of this project is to

Trang 11

develop a novel breast cancer targeting method that exploits the selective chemical reactivity of unnatural sialic acids fordelivery of imaging reagents The immediate application is a new method for non-invasive detection and diagnosis of cancer.Longer-term applications include targeted anti-cancer drugs and vaccines.

DTIC

Breast; Cancer; Imaging Techniques; In Vivo Methods and Tests; Mammary Glands; Sugars

20050173238 Yale Univ., New Haven, CT USA

Predoctoral Training Program in Breast Cancer Research

Stern, David F.; Aug 2004; 18 pp.; In English

Breast cancer is one of the leading causes of cancer deaths of women in the USA Fortunately, this disease is no longer

a ‘black box’ that can only be studied empirically Recent advances in understanding of normal mammary development andcarcinogenic processes have identified a number of specific genes and processes that are dysregulated in breast cancer Thismeans that research on breast cancer has finally advanced to the stage where a concentrated effort in translational research willyield great strides in detection, diagnosis, and treatment The Molecular Medicine graduate training program at Yale wasrecently developed to address these issues This program was developed to offer an interdisciplinary course of study that willfoster an integrated view of disease, built upon a rigorous foundation of basic sciences The emphasis on disease mechanismsand translational research is unique to Molecular Medicine, and distinguishes it from other pre-doctoral programs at Yale ThePredoctoral Training Program in Breast Cancer Research will recruit individuals interested in careers in breast cancer research

to the Molecular Medicine Program, provide specialist training in breast cancer-specific areas, and integrate their trainingexperience with scientists and clinicians investigating breast cancer at Yale

DTIC

Breast; Cancer; Education; Mammary Glands; Medical Science

20050173239 Texas Univ., Houston, TX USA

Training Program in Breast Cancer Research at the University of Texas M.D Anderson Cancer Center

Hung, Mien-Chie; Sep 2004; 28 pp.; In English

With the continuous funding from the US army/DOD (with an one-year no extension cost), the training program on breastcancer research at MDACC has had a successful fifth year The training program has supported three pre-doctoral trainees lastyear and total 16 predoctoral and 16 postdoctoral fellows were supported by the program during the funding period Eachtrainee has made notable progress as evidenced by publications and presentations at national meetings Significant strides havebeen made within the scope of the original specific aims in the following research areas: therapeutic approaches for breastcancer through regulation of oncogene and tumor suppressor gene expression, and control of signal transduction andapoptosis; use of animals to understand the biology of breast cancer and to provide models for preclinical therapeutic andpreventive studies; and The basis biology of breast cancer The goal of the training program is to further the successful training

of fellows who will develop research programs of their own which continue to tackle problems of breast cancer Overall, it

is a very successful program as evident from the numerous publications in peer-reviewed journals (listed in APPENDIX 4).DTIC

Breast; Cancer; Clinical Medicine; Education; Mammary Glands; Medical Science

20050173240 Hutchinson (Fred) Cancer Research Center, Seattle, WA USA

Regulation and Function of the Ipl1/Aurora Kinase

Kotwaliwale, Chitra; Biggins, Sue; May 2004; 10 pp.; In English

Ipl1p is the budding yeast member of the highly conserved Ipl1/Aurora kinase family Ipl1p is required for chromosomebiorientation and the spindle checkpoint Previous work done in the Biggins laboratory uncovered new functions for Ipl1p inspindle disassembly and spindle orientation Ipl1p localizes to the spindle midzone during anaphase and tracks the plus ends

of the depolymerizing spindle MTs Cells lacking Kip3p, a MT destabilizing kinesin, are delayed in spindle breakdown similar

to Ipl1 mutants It is possible that Ipl1p regulates spindle breakdown by directly regulating Kip3 activity We found that Kip3p

Trang 12

is phosphorylated by Ipl1p in vitro and is a phospho-protein in vivo Mutating one of the Ipl1p consensus sites in Kip3pgenerates a spindle disassembly delay similar to ipl1 and kip3DELTA mutants We are currently testing whether the Kip3p isphosphorylated by Ipl1p in vivo In addition we have uncovered a new role for Ipl1p in spindle assembly that is independent

of its other functions Ipl1p acts in parallel with Cin8p, a kinesin-like motor protein, in the assembly of a bipolar spindle.DTIC

Auroras; Chromosomes; Mutations; Proteins; Yeast

20050173242 Naval Medical Research Inst., San Diego, CA USA

Case Study: Preparing the Gastroenterology Clinic at Naval Medical Center San Diego (NMCSD) for T-NEX Implementation

Adams, Brent N.; Apr 2004; 71 pp.; In English; Original contains color illustrations

The objective of this study was to develop a strategy to prepare for the next generation of managed care support contracts

at the clinic level The study will identify areas of concern within the Gastroenterology (GI) clinic that result in the loss ofPrime patients to the contractor, determine if those losses are appropriate, and recommend possible solutions and betterbusiness practices The study analyzed data involving a five-step process that includes evaluating resource allocation andproductivity, referral tracking and variation, provider profiling, appointment utilization / template management, and costs.Based on this study, the clinic should increase bookable hours for staff providers from six to seven hours The clinic shouldalso continue with the revised referral / disengagement process currently in place and continue to provide education andtraining to primary care providers Through analysis of in-house and network costs, 13 procedures and diagnoses wereidentified that should be either performed in-house or referred to the network that result in a cost savings to the GI clinic ofover $90,000 By referring these procedures to the network, access and capacity will be greatly improved

DTIC

Cost Effectiveness; Diseases; Gastrointestinal System; Resources Management

20050173244 Brentwood Biomedical Research Inst., Los Angeles, CA USA

Interactions of Subsymptomatic Doses of Sarin with Pyridostigmine -Neurochemical, Behavioral, and Physiological Effects

Scremin, Oscar U.; Shih, Tsung-Ming; Jenden, Donald J.; Mar 2005; 49 pp.; In English

This report describes the effects of treatment of male Sprague-Dawley rats with low levels of the cholinesterase (ChE)inhibitors Sarin (0.5 LD50 s.c 3 times weekly) and pyridostigmine bromide (PB, 80 mg/L in drinking water) alone or incombination for 3 weeks as compared with untreated controls The work during this reporting period included analysis oflocomotor activity (LA) and autonomic control of heart rate (HR), as well as the metabolism of acetylcholine (ACh) andcholine (Ch), at 2, 4 and 16 weeks after exposure to the ChE inhibitors HR, derived from electrocardiogram, and LA werestudied by radiotelemetry of animals in their home cages 24 hrs a day, during one week ChE inhibitors decreased HR andenhanced HR variability 2 weeks post-treatment, but the effects did not persist until later times No treatment-related changes

in LA were found The expected regional variations in ACh, ACh turnover, and D4Ch, similar to the distribution of othercholinergic markers, or related to characteristics of the blood-brain barrier were found, but ACh and Ch contents were alteredonly at two weeks post-treatment No treatment-related effects were detected in ACh turnover In conclusion, changes in thevariables under study were mainly observed 2 weeks after treatment but failed to persist until later intervals Thus, theseexperiments do not support the hypothesis that exposure to low levels of cholinesterase inhibitors could induce persistent ordelayed effects in control of heart rate and locomotion or cholinergic metabolism

DTIC

Acetyl Compounds; Acetylcholine; Autonomic Nervous System; Choline; Cholinesterase; Dosage; Physiological Effects

Relationships of Stress Exposures to Health in Gulf War Veterans

Fairbank, John A.; Oct 2004; 30 pp.; In English

Despite nearly a decade of research, lack of consensus remains about the precise nature, etiology, and significance of Gulf

Trang 13

War veterans’ health concerns No widely accepted case definition for Gulf War illness exists and controversy persists aboutwhether Gulf War veterans symptoms ‘should be considered primarily a part of a general phenomenon that occurs in everywar or a consequence of events and exposures unique to the Gulf War’ (Steele, 2001, p 406) In an effort to further elucidatethe nature of ill-health among Gulf War veterans, we conducted a latent class analysis of symptoms reported in the TenthAnniversary Gulf War Veterans Health Study, a national population-based survey of U.S Gulf War veterans Specifically, wesought to identify subgroups of Gulf War veterans with distinct patterns of symptoms and to determine if such subgroups could

be distinguished with respect to Gulf War exposures and probable posttraumatic stress disorder (PTSD) Additionally, wesought to examine the functional consequences of specific patterns of ill-health and probable PTSD ten years after the PersianGulf War

DTIC

Disorders; Exposure; Gulfs; Health; Mental Health; Persian Gulf; Warfare

20050173246 USA Medicine Inst for Health Studies, Washington , DC USA

Decisionmaker Forums

Tomich, Nancy E.; Mar 2005; 21 pp.; In English

The U.S Medicine Institute for Health Studies, a nonprofit entity devoted toward enhancing communication amongfederal agencies and between federal agencies and the private sector, conducts forums and smaller roundtable discussions atwhich high-level officials engage in frank discussion of issues of current import to federal health programs During 2004, theInstitute addressed these issues: the value of long-term studies (forum); healthcare for reserve forces (roundtable); mentalhealth services for veterans (roundtable); and the future beyond the electronic health record (roundtable) Results of thosediscussions are presented in this report Results are disseminated to key federal and congressional offices and made available

on the U.S Medicine Institute for Health Studies website: www.usminstitute.org

DTIC

Command and Control; Decision Making; Medical Services; United States

20050173247 Kansas Univ Center for Research, Inc., Lawrence, KS USA

Synthesis of Cryptophycin Affinity Labels and Tubulin Labeling

Yang, Kyounglang; Georg, AGunda I.; May 2004; 18 pp.; In English

Cryptophycins are a potent, tumor-selective class of tubulin-binding antimitotic anticancer agents with excellent activityagainst MDR cancers For the development of these promising compounds into useful chemotherapeutic agents, detailedinformation about the binding domain of the cryptophycins is essential We plan to map the cryptophycin binding site throughphotoaffinity labeling studies Toward this goal we have prepared ClO azido analogues of cryptophycin-24 and have evaluatedthem in a tubulin assembly assay We have found them to be potential candidates for photoaffinity labeling studies.DTIC

Cancer; Marking; Neoplasms

20050173252 Army Research Inst of Environmental Medicine, Natick, MA USA

Technologies for Metabolic Monitoring Military Section Editorials in Diabetes Technologies and Therapeutics

Friedl, Karl E.; Dec 2004; 27 pp.; In English

Special Congressional Interest funds appropriated for diabetes ambulatory monitoring have supported dual use research

in the ‘Technologies for Metabolic Monitoring’ program, managed by the Military Operational Medicine Research Program(USAMRMC) The U.S Army Research Institute of Environmental Medicine (USARIEM) integrates new knowledge andtechnology developed from the program into metabolic research and monitoring applications for soldiers The DiabetesTechnology Society has been a key forum for dissemination of DoD interests and research results, at the annual Fall meetingsand in a Military Metabolic Monitoring section of Diabetes Technology and Therapeutics Papers feature DoD-supportedresearch, accompanied by editorials that highlight dual military and clinical uses of the research to promote a broader interest

in technology solutions for both applications This report includes reprints of eight MMM editorials that appeared in thejournal (2004-2005) Topics include IGFI monitoring, advanced technology, hyperspectral imaging accelerometry, foot-strike

Trang 14

monitoring, ConA-based sensors, lactate sensors, and tissue responses to implants.

DTIC

Metabolic Diseases; Metabolism; Therapy

20050173256 Texas Univ Health Science Center, Houston, TX USA

Disaster Relief and Emergency Medical Services Project (DREAMS TM): science, Triage and Treatment (STAT)

Casscells, S W.; Oct 2004; 119 pp.; In English

Science, Triage, and Treatment:STAT is the component of DREAMS (Disaster Relief and Emergency Medical Services)that is developing new ways to diagnose and treat tissue injuries and infection Progress been the pathophysiology andmolecular biology of anthrax, human cytochrome P45O defenses, inflammatory oxidation, apoptosis, reperfusion injury, organfailure, and nitric oxide New techniques have been developed to automatically diagnose ischemia and heart, kidney, andrespiratory failure STAT science have also developed new techniques to diagnose and image tissue inflammation and necrosisusing CT, magnetic resonance, thermal imaging% and near-infrared spectroscopy These have led to numerous publications,patents, products, clinical trials, and awards In addition to trauma and infection, likely applications include atherosclerosis andcancer In summary, DREAMS-STAT is making better the expected progress toward its goal of improving the care ofbattlefield injuries

DTIC

Disasters; Dreams; Emergencies; Medical Services

20050173257 Academy of Health Sciences (Army), Fort Sam Houston, TX USA

The Military Healthcare System Third Party Collection Program: Analyzing the Effectiveness of the Other Health Insurance (OHI) Information Collection Process

Weinberg, Edward J.; Jul 2004; 58 pp.; In English

The purpose of this research was to assess the effectiveness of the OHI information collection process in a uniformedservices military treatment facility (MTF) 442 OHI surveys were administered to beneficiaries presenting civilianprescriptions to the MTF outpatient pharmacy from 01 to 29 February 2004 The average level of OHI present in the sampleanalyzed was 31.9 percent OHI was regressed upon predictor variables consisting of zip code, age group, beneficiary category,TRICARE Prime enrollment, average number of prescription drugs required per month, and percentage of time the MTF isused for prescription drug needs Multiple linear regression results indicated a statistically significant relationship in theprediction of having OHI, with R2 = 192, F (13, 428) = 7.829, p \h.0001 Further hypothesis tests with hierarchical multipleregression analyses indicated that all predictor variables made substantive unique contributions to having OHI with theexceptions of the number of drugs per required per month and the zip code to the beneficiaries’ place of residence The results

of the OHI survey were used to conduct an abbreviated business case analysis With complete OHI information, third partycollections for filling civilian prescriptions alone could conservatively be increased from $3,490 to $403,146 annually.DTIC

Health; Insurance (Contracts); Modulation Transfer Function

20050173265 Connecticut Univ., Storrs, CT USA

Ultrasound Assisted Optical Imaging

Chen, Nan G.; Zhu, Quing; Nov 2004; 8 pp.; In English

We are continually conducting clinical experiments at the UConn Health Center and Hartford Hospital The statisticalanalysis of the first 65 cases (including 8 cases of cancers and 57 cases of benign lesions) shows strong correlation betweenthe total hemoglobin concentration and malignance There is about two-fold increase in the total hemoglobin concentrationfor cancers compared with the typical values for benign lesions This agrees with our hypothesis that optically availableparameters can significantly improve the accuracy of breast cancer detection To further improve the performance of opticalimaging system, we are pursuing the time-resolved method We have developed a time-resolved diffusive optical tomographysystem via a novel spread spectrum approach A low power (%5 mW) laser diode modulated with pseudo-random bitsequences replaces the short pulse laser used in conventional time-resolved optical systems, while the time-resolved

Trang 15

transmittance is retrieved by correlating the detected signal with the stimulation sequence Temporal point spread functions

of diffusive light propagating through a turbid medium have been measured with remarkably low noise levels 2-dimensionalscanning imaging experiments were performed to demonstrate the great potential of this new imaging technique.Sub-nanosecond temporal resolution (approx 0.9 ns) has been achieved

DTIC

Cancer; Imaging Techniques; Ultrasonics

20050173274 California Univ., Los Angeles, CA USA

The UCLA-Community Breast Cancer Collaborative Clinical Translational Research Program

Glaspy, John A.; Oct 2004; 10 pp.; In English

The purpose of this proposal was to develop a consortium of community physicians committed to study novel approaches

to the treatment and prevention of breast cancer, provide them with a clinical trials infrastructure linked to an academic centerwith expertise in basic research and the design and regulation of clinical investigation and to form partnerships with thepharmaceutical industry to facilitate the rapid translation of novel therapeutic approaches to breast cancer At the time of ourmost recent annual progress report, we had succeeded in opening additional research sites aimed at increasing participation

by patients from underserved populations, and initiating new, investigator-initiated clinical trials Over the last year of support,the clinical trials network continued to expand and additional breast cancer clinical trials were initiated Due to a variety ofchallenges being faced at most academic institutions, over the last two years accrual to clinical trials of patients with cancersother than breast cancer within the UCLA-CORN has decreased Due to the enhanced support provided through this proposal,

we were able to sustain our annual growth in accrual to breast cancer studies

DTIC

Breast; Cancer; Clinical Medicine; Mammary Glands

20050173275 Baylor Coll of Medicine, Houston, TX USA

Identification of Signaling Proteins the Modulate Androgen Receptor Activity

Songyang, Zhou; Nov 2004; 8 pp.; In English

Androgens and the androgen receptor (AR) play a critical role in the development and progression of prostate cancers.The majority of prostate cancers initially respond to endocrine treatment (androgen dependent), but eventually becomeandrogen independent that prove fatal It appears that a functionally active AR may contribute to the progression ofandrogen-independent prostate cancers Understanding the signaling pathways that regulate androgen-dependent and -independent activation of AR mediated transcription would provide valuable information for finding an ultimate cure for thisdisease We have proposed to identify the signaling components that regulate AR activity using a novel retrovirus- mediatedgenetic system, and to understand the mechanism of how the identified factors control AR activity To this end, we haveestablished and optimized our retrovirus-mediated genetic screen approach The retroviral vectors to be used have beenimproved which will allow high-efficiency mutagenesis and ease of manipulation and analysis We have also made significantprogress towards optimizing our screening strategies and establishing a suitable cell line for the genetic screen With thesetools in hand, we are in the process of performing the genome wide genetic screen to identify genes that are important forandrogen receptor signaling and study how they may contribute to the progression of prostate cancers

DTIC

Cancer; Hormones; Males; Prostate Gland; Proteins

20050173276 Ohio State Univ., Columbus, OH USA

The Combined Impact of Surgery and Immunomodulation With Low Dose Cytoxan and GM-CSF in the Early Treatment of Breast Cancer

Kendra, Kari L.; Sep 2004; 20 pp.; In English; Original contains color illustrations

The purpose of this study was to evaluate the combined impact of surgery and immunomodulation with low dose cytoxanand GM-CSF on the development of dendritic cells and the activation of T cells in vivo MMTV Her2/neu mice, which

Trang 16

spontaneously develop mammary tumors were treated with combinations of cytoxan, GM-CSF and surgery Flow cytometrywas used to evaluate blood (B), lymph nodal tissue (LN), and splenocytes (S) for evidence of monocyte differentiation todendritic cells (DC) Both tumor naive mice and mice with spontaneous tumor growth were evaluated With this study we wereable to identify a subpopulation of monocytic cells with characteristics consistent with partial differentiation to dendritic cellsusing the cell surface markers CD11C, MHC II, CD86/CD40, CD80, and Ly6c While this study was unable to demonstratealteration of the cell surface markers of the monocytic cell populations in a manner consistent with dendritic cell differentiationusing GM-CSF or cytoxan, this study suggests that the presence of tumor itself may alter the CD40 and MHC II level in thespleen and that the presence of tumor itself may lead to early differentiation of the dendritic cell population in the spleen.DTIC

Breast; Cancer; Colonies; Crystal Structure; Dendritic Crystals; Dosage; Leukocytes; Macrophages; Mammary Glands; Stimulation; Surgery

20050173277 Kentucky Univ., Lexington, KY USA

Dietary Lipids, Cell Adhesion and Breast Cancer Metastasis

Toborek, Michal J.; Oct 2003; 90 pp.; In English; Original contains color illustrations

Excessive consumption of dietary fat may enhance the rate of breast cancer metastasis In addition, it is generally acceptedthat the upregulation of endothelial cell adhesion molecules is involved in the formation of blood-borne metastasis Amongdifferent adhesion molecules, evidence indicates that intracellular adhesion molecule-1 (ICAM-1) may play a critical role inbreast cancer metastatic formation Our studies have demonstrated that dietary fatty acids can exert highly specific effects onNF-kB activation and expression of adhesion molecules in human endothelial cells In addition, we indicated that linoleic acidinduces ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) expression through the activation of NF-kB Moreimportantly, because the ability of cancer cells to interact with the endothelium appears to be a prerequisite for the potential

of distant metastasis and because ICAM-1 and VCAM-1 are considered to be a crucial adhesion molecule in this process, thepresent study may have significant therapeutic implications in developing a novel strategy against cancer metastasis.DTIC

Adhesion; Breast; Cancer; Diets; Fatty Acids; Lipids; Mammary Glands; Metastasis; Molecules; Nutrition

20050173278 Northwestern Univ., Evanston, IL USA

Suppressive Role of Androgen-Response Gene Calreticulin in Prostate Cancer

Wang, Zhou; Dec 2004; 18 pp.; In English

Androgens are intimately associated with prostate cancer progression One of the androgen-response genes encodescalreticulin, a highly conserved protein with demonstrated functions in intracellular Ca++ homeostasis, cell adhesion,chaperoning, and gene expression Our studies showed that calreticulin overexpression is suppressive to tumor growth andmetastasis of prostate cancer cells in orthotopic and subcutaneous xenograft tumor models and calreticulin expression isdown-regulated in human prostate tumor specimens Thus, down-regulation of calreticulin in clinical prostate cancerspecimens is an important step in prostate cancer progression Our observations argue that part of androgen-induced geneexpression program, such as calreticulin, is inactivated in the progression of prostate cancer, which represents a new concept

in prostate cancer biology In the present study, we have shown that the proline-rich P-domain, which is thought to havelectin-like chaperoning activity, is responsible for the suppression of prostate tumor growth Our results provide strong basisfor further exploring the mechanism by which calreticulin suppresses prostate tumor progression

DTIC

Cancer; Hormones; Males; Prostate Gland; Retarding; Suppressors

20050173279 Illinois Univ., Chicago, IL USA

1 ALPHA-Hydroxyvitamin D5 as a Chemotherapeutic and Possibly Chemopreventive Agent

Das Gupta, Tapas K.; Sep 2004; 95 pp.; In English

We identified a novel vitamin D analog, 1 alpha-hydroxy-24 ethyl vitamin D5 (1 alpha(OH)D5) that showed potent

Trang 17

growth inhibitory and cell-differentiating actions in breast cancer cells Based on our findings in vitro and in vivo, wehypothesized that 1 alpha(OH)D5 (D5), when administered to women with breast cancer, will induce differentiation ofdedifferentiated cells and thereby prevent progression of malignancy In 1999-2000, we completed preclinical studies in rats,showing that D5 has no serious toxicity; high doses led to a hypercalcemic effect, which was reversible In vitro studiesshowed that D5 has no effect on normal breast epithelial cells but induces apoptosis in breast cancer and showed apoptoticeffect in fibroadenomas In 2000-2001, under GMP, we completed preclinical toxicity studies in dogs and completed synthesis

of 1 alpha(OH)D5 In vitro studies suggested that D5 has no effect on normal breast tissues In 2001-2002, in vitro studiesshowed D5 to have no effect of cell proliferation , cell death, or differentiation markers (casein) in nonmalignant breastepithelial cells In 2002-2003, in vitro studies suggested a differential effect of D5 on ER+ vs ER- cells and that D5’s actionmay be mediated, in part, by VDR Clinical trial protocols were updated for both the UIC IRB and FDA In 2003-2004, theclinical protocol was updated and approved by the UIC IRB, and Lutheran General Hospital was removed from the protocol.Currently, all of the preclinical toxicology and pharmacology studies have been completed and an ND application has beensubmitted to the FDA The FDA has asked for some additional

DTIC

Breast; Calciferol; Cancer; Chemotherapy; Drugs; Health; Mammary Glands

20050173281 Naval Health Research Center, San Diego, CA USA

A Multiplex PCR for Detection of Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, and Bordetella pertussis in Clinical Specimens

McDonough, E A.; Barrozo, C P.; Russell, K L.; Metzgar, D.; Jan 2005; 29 pp.; In English; Original contains colorillustrations

Report No.(s): AD-A432554; NHRC-05-02; No Copyright; Avail: Defense Technical Information Center (DTIC)

A multiplex PCR was developed that is capable of detecting four of the most important bacterial agents of atypicalpneumophia, Mycaplasma pneumoniae, Chlamydophia pneumoniae, Legionella pneumophila, and Bordetella pertussis inuncultured patient specimens These organisms cause similar symptomologies and are often not diagnosed because they aredifficult to identify with classical methods such as culture and serology Given this, the overall impact of these pathogens onpublic health may be grossly underestimated The molecular test presented here provides a simple method for identification

of four common, yet diagnostically challenging, pathogens

DTIC

Bacteria; Microorganisms; Multiplexing

A Comparison of the Post-Deployment Hospitalization Experience of US military Personnel Following Service in the

1991 Gulf War, Southwest Asia After the Gulf War, and Bosnia

Smith, Besa; Smith, Tyler C.; Ryan, Margaret A.; Gray, Gregory C.; Jul 2004; 26 pp.; In English; Original contains colorillustrations

Much attention has been given to the impact of deployment upon the health of veterans from the first Gulf War Whiledifferences in self-reported symptoms have been common, no specific exposures have been implicated Some have suggestedthat stress from deployment is the chief cause for multi-symptom conditions among 1991 Gulf War veterans We sought toexamine the impact of large military deployments upon hospitalization experience Hospitalization records from October1,1988, through December 31,2000, were examined for all active-duty personnel deployed exclusively to the Gulf War,Southwest Asia, or Bosnia Cox’s hazard modeling was used to model time until first post deployment hospitalization,separation from active duty, or December 31, 2000, whichever occurred first, while controlling for influential covariates andtemporal changes In comparison with Gulf War veterans (n = 455,465), personnel deployed to Southwest Asia after the GulfWar (n = 249,047) were at a slight increased risk of hospitalization (hazard ratio = 1.05; 95% confidence interval: 1.02,1 08).However, personnel deployed to Bosnia (n = 44,341) were at decreased risk for any cause hospitalization (HR = 0.69; 95%CI: 0.66, 0.72) While these findings do not fully explain the complexity of post deployment health experiences, they do notsupport the theory of a unique illness in 1991 Gulf War veterans

DTIC

Asia; Bosnia and Herzegovina; Combat; Deployment; Gulfs; Military Personnel; Warfare

Trang 18

20050173284 California Univ., Los Angeles, CA USA

Elucidation of a Novel Cell Death Mechanism in Prostate Epithelial Cells

Baum, Linda G.; Dec 2004; 30 pp.; In English

Tumor cell resistance to apoptosis and immune attack are obstacles to effective prostate cancer therapy Androgendependent LNCaP prostate cancer cells are sensitive to apoptosis induced by galectin-l, a human lectin that is abundant inprostate stroma In contrast, androgen independent LNCaP, DU145 and PC-3 cells are resistant to galectin-l induced death andexpress galectin-l on the cell surface Galectin-l binds to specific saccharide ligands on LNCaP cells to trigger cell death;susceptibility to galectin-1 requires 0-linked glycans on glycoproteins, while N-glycans are not required for galectin-l inducedcell death Galecti-l resistance in androgen independent LNCaP cells correlates with decreased expression of a specificglycosyltransferase, C2GnT, that creates 0-glycan ligands recognized by galectin-l Blocking Oglycan elongation byexpressing a competing glycosyltransferase, ST3Gal I, renders LNCaP cells resistant to galectin-l death Galectin-1 resistantDU145 and PC-3 cells can kill adherent T cells via cell surface gal-1 Moreover, PC-3 cells secrete a factor that up-regulatesgal-1 expression by endothelial cells, which then can kill adherent T cells Thus, enhancing galectin-1 prostate cancer celldeath may allow novel therapeutic approaches to manipulate tumor cell glycosylation to overcome tumor cell resistance toapoptosis and to prevent tumor evasion of the immune response

DTIC

Cancer; Death; Epithelium; Prostate Gland

Department of the Navy Suicide Incident Report (DONSIR): Summary of 1999-2002 Findings

Stander, Valerie A.; Hilton, Susan M.; Kennedy, Kevin R.; Gaskin, Thomas; May 2004; 35 pp.; In English; Original containscolor illustrations

Since 1999, the Department of the Navy (DON) has conducted an extensive suicide surveillance program, using the DONSuicide Incident Report (DONSIR) to collect data on completed suicides in the U.S Navy (USN) and Marine Corps (USMC).The long-term goal of this program is to improve suicide prevention by identifying and modifying military-specific riskfactors The DONSIR significantly improves the capability of the DON to track and analyze data on completed suicides Itprovides the DON with consistent data that can be compared across both the USN and the USMC It establishes baselines forsuicide rates and suicide event characteristics that can be used to track trends over time It also evaluates military-specificcorrelates of suicide, which cannot be evaluated using civilian, academic literature This is the fourth annual report on theDONSIR This report presents findings from the first 4 years of data collected since the program was initiated in 1999 andsummarizes the conclusions and recommendations that can be drawn based on the results to date

DTIC

Navy; Prevention; Risk

20050173288 Anteon Corp., Natick, MA USA

Estimation of Warfighter Resting Metabolic Rate

Doherty, Tammy J.; Apr 2005; 25 pp.; In English

Contract(s)/Grant(s): DAAD16-02-C-0056; Proj-AH99

Report No.(s): AD-A432565; NATICK-TR-05/015; No Copyright; Avail: Defense Technical Information Center (DTIC)The purpose of this study was to identify the best method for estimating the resting metabolic rate (RMR, kcal/h) of thewarfighter, given the current level of available knowledge, using methods and data published in the literature Severalpublished equations for estimating the standard resting metabolic rate (RMRS), defined as the metabolic rate in the morningafter an overnight fast, with the subject at rest in a thermoneutral environment in a supine position, were also evaluated Aseries of comparison data sets of individual data from results published in the literature, in which obese subjects and subjectsyounger than 18 and older than 55 yrs, were eliminated A comparison between estimated RMRS and RMRS values from thecomparison data set showed that equations developed by Mifflin and coworkers in 1990 fit the data the best It was determinedthat once inherent differences in the subject populations used to develop and test the equations were considered, that theequations developed by differences in the subject populations used to develop and test the equations were considered, that theequations developed by Schofield (1985) for the World Health Organization, provided the best fit to the data From linearregression analyses on the comparison data set, it was found that a combination of the estimated lean body mass (computed

Trang 19

from weight, age and gender) and gender or the body weight (W, kg) with gender and age fit the data equally wellSTANDARD ERROR of THE ESTIMATE (SEE = 6.75 kcal/h.

DTIC

Metabolism; Military Personnel; Regression Analysis

20050173333 Army War Coll., Carlisle Barracks, PA USA

Transforming Health Service Capabilities in the Army Reserve

Ritter, Corinne M.; Mar 2005; 23 pp.; In English

The Chief of the Army Reserves LTG James R Helmly in September 2003 provided a plan that addresses the ArmyReserve Bridge to Transformation and it is officially called the Federal Reserve Restructuring Initiative The Federal ReserveRestructuring Initiative is synchronized with the Army’s Transformation Campaign Plan and addresses people readiness andtransformation LTG Helmly identified six imperatives he wants embedded in the transformation of the Reserve Component.The reserve medical community can utilize these six imperatives as a lens to examine transformation The Six ReserveComponent Imperatives are: 1 Reengineer the mobilization process; 2 Transform command and control; 3 Restructure unitsinto a flexible and adaptable force; 4 Improve human resources staff; 5 Build a rotational-based force; and 6 Improveindividual support to combatant commanders The purpose of this strategic research project is to focus on the currenttransformation guidance review current transformation initiatives and consider the implications of these imperatives on thehealth service capabilities in the Army Reserve

DTIC

Health; Medical Services; Reserves

20050173340 Walter Reed Army Medical Center, Washington, DC USA

Walter Reed Army Medical Center Direct Patient Care in Support of the Global War on Terrorism Inpatient Casualties

Cahill, James G.; May 2004; 60 pp.; In English; Original contains color illustrations

Walter Reed Army Medical Center (WRAMC) is the premier medical specialty referral center in the USA Department ofDefense (DOD) and is the leading institution for clinical education and research in the U.S Army (Walter Reed Web Page) WRAMC plays a crucial role in the DOD’s patient evacuation system as the first continental USA (CONUS)-based militarymedical treatment facility to receive soldiers evacuated from European Command (EUCOM) and Central Command(CENTCOM) areas of responsibilities (AORs) Since fall of 2001, WRAMC was received soldiers injured in support of bothOperation Enduring Freedom (GEE) in Afghanistan and Operation Iraqi Freedom (OIE), the two primary operations in theUSA Global War on Terrorism (GWOT) This study was designed to review the composition of initial GWOT inpatientcasualties received at WRAMC and to explore the costs associated with the care provided These results will assist planners

in understanding appropriate levels of resources needed to support future contingency operations Cross-sectional data onprimary diagnosis-related group (DRG) and DRG ‘cost’ were collected for 372 GWOT inpatients admitted to WRAMC inFY03

DTIC

Casualties; Clinical Medicine; Injuries; Patients; Terrorism; Warfare

20050173342 Moncrief Army Community Hospital, Fort Jackson, SC USA

Analysis of Patient Cycle Times at the Urgent Care Clinic at Moncrief Army Community Hospital

Chavez, Jose L.; Jun 2004; 53 pp.; In English; Original contains color illustrations

This study evaluated the patient processing system at the Urgent Care Clinic at Moncrief Army Community Hospital, FortJackson, SC to assess its timeliness and efficiency Analysis of patient cycle times at two separate time intervals made itpossible to identify the different time periods and assess the patient’s access to care A questionnaire was used to evaluate theeffects of changes in this process Although overall wait and access to care improved (p \h 05), no significant improvement

in overall satisfaction was found between the two time intervals Written patient comments indicated a greater concern forpersonal treatment experienced rather than access time to receive care This study underscores the difficulties in identifyingand meeting patient satisfaction and demand

DTIC

Clinical Medicine; Hospitals; Medical Services; Patients

Trang 20

20050173357 Mayo Foundation, Rochester, MN USA

Investigation of Gene Expression Correlating With Centrosome Amplification in Development and Progression of Breast Cancer

Lingle, Wilma L.; Sep 2004; 69 pp.; In English

We previously demonstrated that centrosome amplification correlates with chromosomal instability and loss ofdifferentiation in breast tumors The goal of this research is to identify genes important in breast cancer due to their associationwith amplified centrosomes, We determined that centrosomes are amplified prior to invasion and amplification is maintainedduring progression We identified candidate genes for further investigation Last year, we 1) measured chromosomal instability

in tumors for which we have gene expression and centrosome amplification data, 2) analyzed the relationships between lymphnode and estrogen receptor status, chromosomal instability and centrosome amplification, and 3) developed a collaborativestudy to look at centrosome amplification, chromosomal instability, and gene expression in a rat model of estrogen-inducedmammary cancer During this last reporting period we 1) demonstrated that expression of Aurora-A, a centrosome-associatedkinase, correlates to Nottingham Prognostic Index in human breast tumors, 2) demonstrated that estrogen exposure leads tocentrosome amplification and aurora-A over-expression prior to invasion in a rat mammary tumor model, and 3) developed

a collaboration to study the effects of cyclin D1 overexpression in a mouse model and demonstrated that cyclin D1 inducescentrosome amplification and aneuploidy

DTIC

Amplification; Breast; Cancer; Chromosomes; Correlation; Estrogens; Gene Expression; Genes; Mammary Glands

Graduate Management Project: Optimizing Cardiology and Radiology Services at Evans Army Community Hospital

Geolingo, Harld J.; Jan 2004; 85 pp.; In English; Original contains color illustrations

During fiscal years 2003 and 2004, Evans Army Community Hospital (EACH), Port Carson, Colorado, diligentlyprepared itself to meet the operating challenges under the new TRICARE contracts As part of EACH’s preparation efforts,this study provides an optimization analysis of cardiology and radiology services, utilizing the business case analysis process.The results of this study indicate that a recapture opportunity exist by providing in-house non-invasive echocardiographservices, which would yield a 36-month return on investment (ROI) of $210,000 Additionally, the potential for an 80 percentreduction in radiology purchased care can be realized, provided EACH procures a magnetic resonance imaging device,sustains current staffing levels, and institutes strict referral management under the new TRICARE contracts Furthermore,diagnostic and therapeutic cardiology product lines possessed no recapture opportunity, as recapture efforts would yield anannual net loss exceeding $500,000 The primary cost savings effort under these cardiology product lines would be to negotiate

a discounted reimbursement rate with the Veteran’s Administration (VA) Engaging in these optimizing efforts will increaseEACH’s ability to operate within budgetary limits, and more importantly provide the best health care delivery opt ions to allbeneficiaries to whom EACH serves

DTIC

Cardiology; Hospitals; Medical Services; Radiology

The Open Access Appointment System: A Phased Implementation Approach at Keller Army Community Hospital

Hankins, Steven D.; Apr 2004; 72 pp.; In English; Original contains color illustrations

Concerns about timely access to health care have driven many military health system (MHS) beneficiaries to question theway in which the MHS operates The open access appointment system, based upon a methodology of doing today’s worktoday, will allow Keller Army Community Hospital to address this core aspect of patient satisfaction Purpose: The purpose

of this study was to provide a framework for open access implementation within a small Army Community Hospital whileconcurrently examining the effect a phased implementation approach had on physician satisfaction, provider continuity, andappointment availability Methods: This study is both a qualitative and quantitative, exploratory, descriptive, cross-sectionalstudy of the requirements needed to implement an open access system and the effect a phased implementation has on clinicalpractices Results: The requirements for implementing an open access system center around controlling appointing practiceswithin the facility, effective template management, and effective space utilization Mean levels of provider satisfactionincreased and both provider continuity and appointment wait time improved at statistically significant rates (p\h.01 for each)

Trang 21

Conclusions: This study indicates that open access bas benefited KACH, its staff members, and its beneficiary population.DTIC

Hospitals; Management Systems; Medical Services

Forecasting Medical Materiel Requirements for Contingency Operations

Moroney, Daniel J.; Apr 2004; 110 pp.; In English; Original contains color illustrations

This qualitative study addresses the issue of poor forecasting accuracy for medical materiel requirements in preparation

of contingency operations Using examples from recent operations, to include Operation Enduring Freedom and OperationIraqi Freedom, this paper identifies how planners forecast requirements, highlights roadblocks to successful forecasting, anddescribes tools, models, and procedures for forecasting supplies, both internal and external to the Department of Defense Thestudy concludes that effective forecasting of supplies is accomplished through a collaborative team approach betweenclinicians, planners, and logisticians Additionally, planners and logisticians must look beyond authorizations in sets, kits, andoutfits when planning for patient treatment within a theater of operations Among the various tools discussed, those that basemedical materiel requirements on a time-phased patient driven scenario show the most promise including the Naval HealthResearch Center’s Estimating Supplies Program and Resupply Validation Program and the Army Medical Research andMateriel Command’s Joint Medical Materiel Modeling

DTIC

Contingency; Forecasting; Logistics Management; Medical Services; Military Operations

Analyzing the Requirement for a Deployed Warrior Medical Management Center Table of Distribution and Allowances

at Landstuhl Regional Medical Center

Probus, Mark C.; Feb 2004; 58 pp.; In English; Original contains color illustrations

This study identified personnel, equipment, facilities, evacuation, time, and patient acuity variables within the Department

of Defense Central and European Commands as they pertained to the development of a Separate Table of Distribution andAllowances organization designed to medically manage evacuees during war Three separate analyses were conducted togather the results A qualitative historical analysis of the existing Deployed Warrior Medical Management Center at LandstuhlRegional Medical Center revealed the need for various operational cells for the management of inpatients versus outpatients

A Chi-Square statistical test using a cross tabulation table with an alpha probability set at p(underscored) = 01 was predictive

of the type of patient diagnosis (identified by 1CD9 Codes) during the first 180 days of Operation Iraqi Freedom A total costanalysis identified patterns of financial expense, which suggested that evacuation for treatment at Landstuhl Regional MedicalCenter was more costly than treatment in the Central Command Theater of operations The results of these three separateanalyses support the need for a separate Table of Distribution and Allowances organization under Landstuhl Regional MedicalCenter dedicated to the management of evacuees during times of war and provide a template for further evaluation andplanning for such an organization

DTIC

Deployment; Evacuating (Transportation); Medical Equipment; Medical Services; Military Operations

Breaking the Code to Quality Improvement of Medical Report Translations (A Retrospective Analysis)

Sharpe, Timothy A.; Apr 2004; 54 pp.; In English

Over the past year, the 67th Combat Support Hospital/WMEDDAC has accumulated a backlog of over 4,000 pages ofnetwork provider medical reports awaiting translation Throughout the Europe Regional Medical Command military medicaltreatment facilities have had varying degrees of difficulty with the timely translation of medical reports However, at 4,000pages, the 67th CSH/ WMEDDAC has the greatest amount of accumulated medical reports awaiting translation services Thepatient medical record is a vital component to all medical treatment procedures used by clinical staff as both a history and roadmap to care The purpose of this Graduate Management Project (GMP) is to perform a retrospective analysis to objectivelyreview the medical report translation program and identify obstacles impeding translation services Additionally, a

Trang 22

recommended course of action will be developed to improve translation services and minimize or eliminate medical reportbacklogs.

DTIC

Management Systems; Medical Services; Military Personnel; Quality Control; Translating

An Analysis of Transitional Doctor of Physical Therapy Degrees for the Department of Defense

Stang, J M.; Jan 2004; 52 pp.; In English; Original contains color illustrations

The purpose of this study was to survey DoD physical therapists for their opinions of tDPT programs and compare thecosts of several courses of action (COAs) The majority of DoD therapists are credentialed at the graduate level However,the American Physical Therapy Association vision states that by 2020 physical therapy will be provided by therapists who aredoctors of physical therapy A survey of DoD therapists was conducted to describe the attitudes, opinions, and resourcesavailable within the population Descriptive statistics were computed for the sample The results were used to create threeCOAs that were analyzed for cost and feasibility Two-hundred and two DoD surveys were returned for a response rate of 49%.Sixty four percent of respondents were considering enrolling in a tDPT program and were willing to pay an average of $7,398.Time and cost were the two most frequent factors involved in selecting a tDPT program Several options were identified ascost effective This study represents a critical first step in the DoD to describe its physical therapist population It was used

to develop and assess various COAs designed to meet the APTA’s vision and sustain the DoD’s competitive advantage.DTIC

Defense Program; Therapy

Hospital-Based First Responder Mass Prophylaxis Plan

Massey, Mary S.; Mar 2005; 57 pp.; In English; Original contains color illustrations

As the USA improves its collective awareness and emergency preparedness in the face of increased terrorist activity, moreefforts are being made to create and enhance community readiness for catastrophic events There have been substantial efforts

to improve the nation’s bioterrorism preparedness Better planning, equipment, training, surveillance, and pharmaceuticalcaches have elevated the nation s readiness for biological attacks In order to effectively meet the challenges created by abioterrorism attack, its first lines of defense, the first responders, must be rapidly prophylaxed to allow the continuance of theirmission Many states and localities have tackled the gigantic undertaking of mass prophylaxis plans to providechemoprophylaxis to civilians should the need arise Many cities have developed and tested their plans to provide generalpublic mass prophylaxis It is assumed, or briefly mentioned, that the mass prophylaxis of first responders will occur, but fewplans have been developed The primary objective of this research is to develop, test, and make recommendations for astraightforward, adaptable mass prophylaxis plan to meet the prophylactic requirements of local first responders in the event

of a biological attack

DTIC

Emergencies; Health; Hospitals; Maintainability; Prophylaxis; Transponders

20050173373 Northern California Inst for Research and Education, San Francisco, CA USA

Controlled Cortical Impact in Swine: Pathophysiology and Biomechanics

Manley, Geoffrey T.; Rosenthal, Guy; Lam, Maggie; Morabito, Diane; Yan, Donghong; Derugin, Nikita; Bollen, Andrew;Knudson, M M.; Panter, S S.; Mar 2005; 36 pp.; In English

Contract(s)/Grant(s): N00014-02-1-0203

A Controlled cortical impact (CCI) device was used to generate a focal lesion in 23 anesthetized male Yorkshire swine

In 10 swine CCI parameters of velocity and dwell time were varied to achieve a consistent injury (3.5 m/sec, 400 m/sec,respectively) In 13 swine depth of depression was varied from 9 to 12 mm Physiological data including heart rate (HR), meanarterial blood pressure (MAP), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were collected for 10 hoursafter injury Following injury, ICP and HR increased above baseline values in all swine with a more pronounced elevation inanimals impacted to a depth of depression of 12 mm An 11 mm depth of depression was found to most closely mimicpathological features of human TBI with edema, infiltration of inflammatory cells, pericapillary hemorrhage, and petechial

Trang 23

hemorrhages in the white matter Injury to a depth of depression of 12 mm resulted in cortical laceration obscuring thesefeatures Immunohistological staining with Neu-N, MAP-2, and Fluoro Jade B revealed evidence of degenerating neurons,axonal disruption, and impending cell death These results indicate that the swine model of CCI results in a defined andreproducible injury with pathological features similar to human TBI.

DTIC

Biodynamics; Impact Tests

Rapid Identification and Strain-Typing of Respiratory Pathogens for Epidemic Surveillance

Ecker, David J.; Sampath, Rangarajan; Blyn, Lawrence B.; Samant, Vivek; Russell, Kevin; Freed, Nikki; Barrozo, Chris; Wu,Jianguo; Rudnick, Karl; Desai, Anjali; Apr 2003; 13 pp.; In English; Original contains color illustrations

Report No.(s): AD-A432737; BUMED-03-19; No Copyright; Avail: Defense Technical Information Center (DTIC)

Epidemic respiratory infections are responsible for extensive morbidity and mortality within both military and civilianpopulations We describe a methodology to examine respiratory samples that simultaneously identifies broad groups ofbacteria The process uses electrospray ionization mass spectrometry and base composition analysis of broad-range PCKamplification products The base composition analyses from a small set of broad-range primer pairs are used to ‘triangulate’the identity of pathogenic organisms present in the sample Once a species has been identified, the rapid recursive use ofspecies-specific primers to housekeeping genes allows strain-typing This strategy was used to examine samples from militaryrecruits sickened in a recent Group A streptococcal (GAS) pneumonia outbreak (MMWK 52, 6, p106-109, 2003) Thestrain-typing results were essentially identical to those obtained using classic emm typing and Multi Locus Sequence Typing.This method allows real-time evaluation of patient samples and will make possible more rapid and appropriate treatment ofpatients in an ongoing epidemic, regardless of the etiology, in a time frame not previously achievable

DTIC

Epidemiology; Infectious Diseases; Microorganisms; Pathogens; Respiratory System; Surveillance

Pharmacy Wait Time and Prescription Errors at the Dwight D Eisenhower Army Medical Center Outpatient Pharmacy: A Study of Manpower and Customer Service Initiatives

Bonds, Kevin M.; Mar 2004; 48 pp.; In English; Original contains color illustrations

A retrospective study was undertaken at the Eisenhower Army Medical Center to investigate the probable cause andpossible solutions to increased waiting room time for patients and prescription errors The study examined data from a22-month period (January 2002 through October 2003) Two multiple variant regression analyses were performed usingaverage monthly pharmacy waiting room time and average monthly prescription errors as dependent variables and categories

of personnel as independent variables The results of both regression analyses presented strong evidence that the decrease inpharmacy staff over the 22-month period contributed to both the increase in waiting room time for patients and the increase

in prescription errors The correlations between the dependent and independent variables in the regression analyses werestatistically significant Finally, the paper compared and contrasted the bank teller concept, which is the current businesspractice used in the Eisenhower Pharmacy, and other concepts The use of automation and a system that would mandate call-inprescription refills were the primary recommendations that resulted from the comparisons These two methods will most likelyallow the pharmacy to maintain acceptable wait time and produce acceptable levels of prescription errors despite fluctuations

in personnel

DTIC

Errors; Manpower; Pharmacology; Time Measurement

Development of a Provider Profiling Tool for Reappointment

Wallace, Melissa A.; Jul 2004; 62 pp.; In English

Provider profiling is simply measuring a process and/or outcome and comparing it to some defined norm Profiling hasmany uses: utilization management, cost-effectiveness review, meeting access standards, patient satisfaction, outcomesassessment, population health, etc Unfortunately, providers have had a very negative reaction to profiling, a tool that can helpthem improve outcomes and make their practices more efficient This paper will explore the reasons for the negative reactions,

Trang 24

the keys to a successful profiling system, and the various attributes of good measures The purpose of this project is to develop

a tool that will aid in meeting the profiling requirements established by the Joint Commission on Accreditation of HealthcareOrganizations and to use the tool for ongoing quality improvement This paper examines the existing profiling system of asmall, rural Army hospital and describes the development of a new database Given that many Army hospitals are strugglingwith the development of an adequate profiling system, this database may prove useful in developing the groundwork to thosefacilities

DTIC

Data Bases; Health; Medical Services; Mission Planning

Precursor to the TRICARE Next Generation Program

Allen, Tracy L.; Jun 2004; 131 pp.; In English; Original contains color illustrations

The TRICARE Next Generation Program (T-NEX) will be fully implemented in 2004 and will create significant changes

at the military treatment facility level Military treatment facilities will be required to develop comprehensive business plansthat fully document their accountability and responsibility in providing care for enrolled beneficiaries Wilford Hall MedicalCenter is located in the San Antonio multiple-service-area-market within the newly designated South region Within SanAntonio, the Air Force operates Wilford Hall Medical Center, Randolph Clinic, and Brooks City-Base Clinic and the Armyoperates BAMC Medical Center, as well as several smaller troop medical clinics Wilford Hall has been designated as themulti-market manager and, as such, will be expected to formulate one consolidated business plan for the San Antonio marketarea This study seeks to create a service-area profile specific to the 59th Medical Wing, Wilford Hall to assist with developing

a picture of how resources are presently used to meet the needs of the population It contains a structural proposal to go forth

to manage this market area Demographic information for beneficiaries accessing care at Wilford Hall Medical Center wasgathered utilizing data gleaned from the TRICARE Operations Center and customized queries from the Composite HealthCare System Results from a recent data envelopment analysis study were summarized to reveal trends in efficiency levels forWilford Hall Medical Center The paper concludes with the observation that current market management efforts are notsufficiently bold or far-reaching Through the focused efforts of a revised Bexar County Community Health Collaborative, SanAntonio could become an ideal community for delivering medical care in a cost effective way, on time and on target, with thegoals that were set forth in healthier communities

DTIC

Clinical Medicine; Medical Services

20050173389 Minnesota Univ., Minneapolis, MN USA

An Efficient Docking Algorithm Using Conserved Residue Information to Study Protein-Protein Interactions

Duan, Yuhua; Reddy, Boojala V.; Kaznessis, Yiannis N.; Dec 2004; 9 pp.; In English; Original contains color illustrationsContract(s)/Grant(s): DAAD10-01-2-0014

Many protein-protein docking algorithms generate numerous possible complex structures with only a few of themresembling the native structure The major challenge is choosing the near-native structures from the generated set Recently

it has been observed that the density of conserved residue positions is higher at the interface regions of interacting proteinsurfaces, except for antibody-antigen complexes, where a very low number of conserved positions is observed at the interfaceregions In the present study we have used this observation to identify putative interacting regions on the surface of interactingpartners We studies 59 protein complexes, used previously as a benchmark dataset for docking investigations We computedconservation indices of residue positions on the surfaces of interacting proteins using available homologous sequences ofinteracting proteins using available homologous sequences and used this information to filter out from 55% to 88% ofgenerated docked models, retaining near-native structures for further evaluation We used a reverse filter of conservation score

to filter out the majority of non-native antigen-antibody complex structures For each docked model in the filtered subsets, werelaxed the conformation of the side chains by minimizing the energy with CHARMM We then calculated the binding freeenergy using a generalized Born method and solvent accessible surface area calculations Using the free energy along withconservation information and other descriptors used in the literature for ranking docking solutions, such as shapecomplementarity and pair-potentials, we developed a global ranking procedure that significantly improves the docking results

by giving top ranks to the near-native complex structures

DTIC

Algorithms; Docking; Molecular Interactions; Proteins; Residues

Trang 25

20050173390 Children’s Hospital, Boston, MA USA

Prevention of the Angioenic Switch in Human Breast Cancer

Folkman, Judah; Mar 2005; 26 pp.; In English; Original contains color illustrations

The overall goal of this research is to determine if human breast cancer can be prevented from becoming angiogenic when

it is still at a microscopic size of less than approximately 1 mm(sub 3) We have made the following progress during the pastyear: (1) We have developed models in SCID mice of four different non-angiogenic human breast cancers, and have shownthat the time to the switch to the angiogenic phenotype is predictable and reproducible for each different breast cancer type.The same is true for the percentage of tumors that become angiogenic (2) Two angiogenesis-based biomarkers have beendeveloped to detect the angiogenic switch when these tumors are still at a microscopic size of 1 mm(sub 3) or less The mostsensitive and accurate biomarker is the ‘platelet angiogenic profile,’ which determines and quantifies the angiogenic regulatoryproteins being elaborated by a tumor A second biomarker is a rise in circulating precursor endothelial cells exiting from thebone marrow and stimulated by a tumor that is undergoing the angiogenic switch Our translational goal is to treat humanbreast cancer, both primary and recurrent, with non-toxic angiogenesis inhibitors guided by biomarkers before tumors can beanatomically located

DTIC

Angiogenesis; Breast; Cancer; Mammary Glands; Prevention; Switches

20050173397 Walter Reed Army Inst of Research, Washington, DC USA

The Sensitivities of Yeast Strains Deficient in PDR ABC Transporters to Quinoline-Ring Antimalarial Drugs

Emerson, Lyndal R.; Skillman, Bradley C.; Wolfger, H.; Kuchler, K.; Wirth, D F.; Mar 2004; 8 pp.; In English

Contract(s)/Grant(s): DAAG55-98-1-0186; DAMD17-98-1-8003

Data indicate a potential role for the Pdr5p P-glycoprotein ATP-binding-cassette (ABC) transporter in mediatingchloroquine sensitivity in S cervisae This is consistent with the hypothesis that such a transporter plays a role in mediatingquinoline-drug resistance in P falciparum, and complements the results of previous studies on the parasite Additional geneproducts also play a major role in mediating chloroquine sensitivity and resistance, apparently through the modulation ofvacuolar pH in the parasite

DTIC

Chlorine Compounds; Drugs; Quinoline; Sensitivity; Transporter; Yeast

20050173405 California Univ., Berkeley, CA USA

Cooperative Interactions During Human Mammary Epithelial Cell Immortalization

Yaswen, Paul; Jul 2004; 14 pp.; In English; Original contains color illustrations

Our laboratories have developed and utilized cultured human mammary epithelial cells (HMEC) to gain information onthe defects in growth control processes that allow finite lifespan HMEC to overcome all senescence barriers, reactivatetelomerase, and gain immortal potential We hypothesize that, due to the stringency of telomerase repression in humans,attaining these defects may be rate-limiting in human carcinogenesis Our goal is to define the minimum number of geneticand epigenetic changes that permit telomerase reactivation and immortal transformation of finite lifespan HMEC, in a mannerthat models changes observed in breast cancers in vivo Thus far, we have been able to obtain immortalized HMEC using acombination of two oncogenes (c-myc and ZNF217) with pathological relevance to human breast cancer Although CGHanalyses of some of these immortal lines did not show any detectable large-scale changes in gene copy numbers, these lineshave all undergone clonal selection, suggesting that unknown stochastic changes, in addition to over-expression of c-myc andZNF217, might be necessary for immortalization We are currently working to identify these stochastic changes Betterunderstanding of the underlying molecular changes involved in telomerase reactivation may provide novel preventionstrategies and/or targets for therapeutic intervention in breast cancer pathogenesis

DTIC

Aging (Biology); Breast; Cancer; Enzymes; Mammary Glands

Trang 26

20050173412 Delaware Univ., Newark, DE USA

The Ultra High Density Storage of Non-Biological Information in a Memory Composed of DNA Molecules

Chen, Junghuei; Wang, Yuzhen; Deaton, Russell; Dec 2004; 3 pp.; In English; Original contains color illustrationsReport No.(s): AD-A432825; No Copyright; Avail: Defense Technical Information Center (DTIC)

We have designed and performed a proof-of-principle experiment that demonstrates that huge amounts of non-biological,

or abiotic, information can be stored in a memory composed of DNA molecules The preliminary experiment emphasizes onachieving a practical design motivates several fundamental questions such as the amount of information that can be stored in

a DNA memory before errors are introduced, and practical and cost-effective ways of mapping abiotic data onto DNAsequences

DTIC

Computer Storage Devices; Deoxyribonucleic Acid; Molecules

20050173422 Naval Research Lab., Bay Saint Louis, MS USA

Evaluation of Deoxygenation as a Corrosion Control Measure for Ballast Tanks

Lee, Jason S.; Ray, Richard I.; Lemieux, Edward; Little, Brenda J.; Apr 2005; 36 pp.; In English

Report No.(s): AD-A432839; NRL/PP/7303 04-0004; No Copyright; Avail: CASI;A03, Hardcopy

Field experiments designed to evaluate deoxygenation of natural seawater as a corrosion control measure for unprotectedseawater ballast tanks demonstrated decreased corrosion in hypoxic (\h0.2 ppm O2) seawater using weight loss and linearpolarization measurements The experiments also demonstrated the difficulty of maintaining hypoxic seawater Using a gasmixture it was possible to displace dissolved oxygen in natural seawater However, aerobic respiration and corrosion reactionsconsumed oxygen and produced totally anaerobic conditions within the first days of hypoxia When gaskets and seals failedoxygen was inadvertently introduced The impact on corrosion depended on the amount of dissolved oxygen in the system atthe time of the inadvertent oxygen introduction Steels exposed to cycles of hypoxic seawater and oxygenated atmosphere hadthe highest corrosion rate and severity

DTIC

Ballast (Mass); Corrosion; Deoxygenation; Sea Water; Tanks (Containers)

20050173431 Department of Defense, Arlington, VA USA

Acquisition: Direct Care Medical Services Contracts

Young, Shelton R.; Joseph, Michael A.; Grady, Scott J.; Borum, Dawn; Parrish, Robin; Epps, John S.; Lanyi, William F.;Whitehead, Lynnell E.; Zahn, Eva M.; Shifflett, Elizabeth L.; Jun 2004; 52 pp.; In English

Report No.(s): AD-A432855; IG/DOD-D-2004-094; No Copyright; Avail: Defense Technical Information Center (DTIC)The Under Secretary of Defense for Acquisition, Technology, and Logistics is the adviser to the Secretary and the DeputySecretary of Defense for all matters relating to the DoD acquisition system and to procurement The Office of the AssistantSecretary of Defense (Health Affairs) exercises authority, direction, and control over the facilities, funding, personnel,programs, and other medical resources within DoD TRICARE is a regionally managed health care program for active dutyand retired members of the uniformed services, their families, and survivors TRICARE bring together the health careresources of the Army, the Navy, and the Air Force and supplements them with purchased care contracts that provide directhealth care through health care institutions and individual providers in the civilian community To help fill needs that cannot

be satisfied through military treatment facilities or through purchased care contracts under TRICARE, the MilitaryDepartments issue direct care medical services contracts to augment the military and civilian staffs In 2002, DoD spent about

$875 million to acquire medical services through direct care medical services contracts, excluding information technologycontracts We reviewed 125 of those contracts, valued at approximately $73 million

DTIC

Defense Program; Medical Services

20050173433 Department of Defense, Arlington, VA USA

Acquisition: Controls Over Purchase Cards at Naval Medical Center San Diego

Jun 2004; 46 pp.; In English

Report No.(s): AD-A432858; IG/DOD-D-2004-096; No Copyright; Avail: Defense Technical Information Center (DTIC)This report is one in a series of reports that satisfies the requirements in section 1007, ‘National Defense AuthorizationAct for Fiscal Year 2003,’ for the Inspector General of the Department of Defense to perform periodic audits of purchase cardprograms The purchase card is a Government-wide commercial charge card available to offices and organizations for the

Trang 27

purchase of goods and services The implementation of purchase card programs in DoD is intended to be a cost-savingbusiness initiative that reforms processes and improves mission effectiveness.

DTIC

Financial Management; Medical Services; Military Operations

20050173434 Walter Reed Army Inst of Research, Silver Spring, MD USA

Whole Blood Robotic Cholinesterase Assay for Organophosphate Exposure -Testing Soldiers, First Responders, and Civilians in the Field and Laboratory

Gordon, Richard K.; Haigh, Julian R.; Garcia, Gregory E.; Feaster, Shawn R.; Doctor, Bhupendra P.; Riel, Michael A.;Lefkowitz, Lee J.; Lenz, David E.; Aisen, Paul S.; Smart, Wilson; Dec 2004; 9 pp.; In English; Original contains colorillustrations

Exposure to organophosphate (OP) chemical warfare agents (CWAs), pesticides, anesthetics, drugs such as cocaine, and

a variety of therapeutic drugs including donepezil or rivastigmine for Alzheimer’s disease reduces red blood cellacetylcholinesterase (RBC-AChE) or serum butyrylcholinesterase (BChE) activity The activity of RBC-AChE and BChE can

be used as potential biomarkers of suppressed and/or heightened function in the central and peripheral nervous systems Forinstance, the toxicity of pesticides is well documented in humans Therefore, blood cholinesterase (ChE) activity can beexploited as a tool for confirming exposure to these agents and possible treatments Yet it is the OP CWAs that are some ofthe most potent and irreversible inhibitors that can produce excessive accumulation of acetylcholine, and a cholinergic crisis

in man leading to paralysis and ultimately death Current assays for measurement of erythrocytebound acetylcholinesterase(RBC-AChE) and serum butyrylcholinesterase (BChE, pseudocholinesterase) require several labor-intensive processing steps,suffer from wide statistical variation, and inter-laboratory comparison is often difficult Techniques currently used include theEllman and microEllman microtiter method, radiometric, amperometric, and delta (delta) pH (modified Michel protocol) used

by the U.S Army’s Cholinesterase Reference Laboratories (CRL) Such methods determine only the serum BChE orRBC-AChE, and require the use of specific ChE inhibitors or sample processing such as centrifugation

DTIC

Anesthetics; Assaying; Blood; Chemical Warfare; Cholinesterase; Drugs; Exposure; Organic Phosphorus Compounds; Robotics; Serums; Transponders

20050173435 Army Medical Research Inst of Infectious Diseases, Fort Detrick, MD USA

Association of Ebola Virus Matrix Protein VP40 with Microtubules

Ruthel, Gordon; Demmin, Gretchen L.; Kallstrom, George; Javid, Melodi P.; Badie, Shirin S.; Will, Amy B.; Nelle, Timothy;Schokman, Rowena; Nguyen, Tam L.; Carra, John H.; Bavari, Sina; Aman, M J.; Apr 2005; 13 pp.; In English; Originalcontains color illustrations

Report No.(s): AD-A432862; USAMRIID-RPP-04-442; No Copyright; Avail: Defense Technical Information Center (DTIC)Viruses exploit a variety of cellular components to complete their life cycles, and it has become increasingly clear thatuse of host cell microtubules is a vital part of the infection process for many viruses A variety of viral proteins have beenidentified that interact with microtubules, either directly or via a microtubule-associated motor protein Here, we report thatEbola virus associates with microtubules via the matrix protein VP40 When transfected into mammalian cells, a fraction ofVP40 colocalized with microtubule bundles and VP40 coimmunoprecipitated with tubulin The degree of colocalization andmicrotubule bundling in cells was markedly intensified by truncation of the C terminus to a length of 317 amino acids Furthertruncation to 308 or fewer amino acids abolished the association with microtubules Both the full-length and the317-amino-acid truncation mutant stabilized microtubules against depolymerization with nocodazole Direct physicalinteraction between purified VP40 and tubulin proteins was demonstrated in vitro A region of moderate homology to thetubulin binding motif of the microtubule-associated protein MAP2 was identified in VP40 Deleting this region resulted in loss

of microtubule stabilization against drug-induced depolymerization The presence of VP40-associated microtubules in cellscontinuously treated with nocodazole suggested that VP40 promotes tubulin polymerization Using an in vitro polymerizationassay, we demonstrated that VP40 directly enhances tubulin polymerization without any cellular mediators These resultssuggest that microtubules may play an important role in the Ebola virus life cycle and potentially provide a novel target fortherapeutic intervention against this highly pathogenic virus

DTIC

Microorganisms; Microstructure; Pathogens; Proteins; Viral Diseases; Viruses

Trang 28

20050173467 Johns Hopkins Univ., Baltimore, MD USA

Identification of Widely Applicable Tumor-Associated Antigens for Breast Cancer Immunotherapy

Bai, Jining; Oct 2004; 10 pp.; In English

This study is a feasibility study of a novel immunotherapeutic strategy for the treatment of breast cancer The rationale

is based upon recent findings that genes belonging to the pp32 family are differentially and alternatively expressed in mosthuman breast cancers In general, benign breast tissues express pp32, a tumor suppressor, whereas breast cancers expresstumorigenic family members, including pp32r1 and pp32r2 Since pp32r1 and pp32r2 are expressed in nearly all breastcancers, but not in normal adult tissues, they may reasonably serve as targets for antigen-specific immunotherapy The purpose

of this study is to identify tumor-associated antigens (TAA) in pp32r1 and pp32r2, then test their suitability in vitro asimmunotherapeutic targets in breast cancer Currently, the animal study is underway If successful, the results may translateinto eventual clinical trials of peptide vaccines or adoptive T cell therapy

DTIC

Antigens; Breast; Cancer; Mammary Glands; Tumors

20050173470 George Washington Univ., Washington, DC USA

The Establishment of an Inflammatory Breast Cancer Registry and Biospecimen Repository

Levine, Paul H.; Aug 2004; 8 pp.; In English

The Inflammatory Breast Cancer (IBC) Registry enrolled its first patient Sept 10, 2002 As of July 31, 2004, 163 patientshave contacted the Registry and 135 have completed their interviews Tissue blocks have been obtained from 110 patients andfrozen surgical specimens have been collected from 10 Five laboratories were sent biospecimens and results continue to beobtained Data on the first 50 patients were presented at the San Antonio Breast Cancer Conference in December 2003 andinitial evaluation of the questionnaire data will be presented at the San Antonio Breast Cancer Conference in December 2004.The clinical data include the observation that approximately one third of IBC patients are initially diagnosed as having mastitisand are treated with up to five months of antibiotics before the diagnosis of cancer is made Less than 25% of patients have

a discrete mass identified on initial mammography Laboratory data thus far (45 patients) indicate that the tumors from allpatients express significant amounts of BP-1, a homeobox gene associated with breast cancer aggressiveness In addition,tumors from a higher percentage of IBC patients express gene sequences resembling mouse mammary tumor virus thannon-IBC breast cancer patients

DTIC

Breast; Cancer; Clinical Medicine; Mammary Glands; Patients

20050173491 Harvard Medical School, Boston, MA USA

Characterization of Two Novel Oncogenic Pathways Collaborting With Loss of p53 or Activated Neu in Mouse Models

of Breast Cancer

Lu, Jianrong; Leder, Philip; Sep 2004; 12 pp.; In English

Cancer is a complex multistep disease and progresses through successive accumulation of genetic mutations Loss oftumor suppressor gene p53 and activation of oncogene Neu/ErB2 are among the most frequent genetic alterations in humanbreast cancer We performed a retroviral insertional mutagenesis screen to identify genes that may contribute to mammarytumor formation in conjunction with deregulated p53 or Neu Multiple proviral insertions from independent tumors wereidentified to be located within introns of the F-box gene Fbw4, suggesting that the structural alteration at this locus mayprovide selective growth advantage The viral integrations result in marked overexpression of a novel, naturally occurringFbw4 short isoform, which is also spontaneously enriched in several mouse and human breast cancer cell lines but not innon-transformed mammary epithelial cells, thus appears to be associated with malignant transformation Overexpression ofthis short isoform in the normal mouse mammary epithelial cell leads to anchorage-independent growth in soft agar Takentogether, these observations indicate that aberrant expression of the short Fbw4 isoform observed in MMTV-induced tumorsand spontaneous breast cancer cell lines may contribute to mammary tumorigenesis

DTIC

Breast; Cancer; Carcinogens; Losses; Mammary Glands; Mice; Tumors

Trang 29

20050173492 Army Inst of Surgical Research, Fort Sam Houston, TX USA

Hypotensive Resuscitation of Casualties in the Far-Forward Combat Environment: Effects of Select Crystalloids and Colloids on Signal Transduction Mediators in a Swine Model of Severe Hemorrhage

Dubick, Michael A.; Cameron, David G.; Sondeen, Jill L.; Majumdar, Adhip P.; Dec 2004; 21 pp.; In English; Originalcontains color illustrations

Hemorrhage remains a major cause of death on the battlefield in conventional warfare (Bellamy 1984) Current dogmadictates that early, adequate fluid resuscitation is crucial to reduce the mortality and morbidity associated with hemorrhagicshock Yet, despite much research in the field and years of resuscitating thousands of patients, the optimal fluid andresuscitation strategy for the treatment of hemorrhagic hypovolemia remains unknown However, with future combatstrategies focused around the Future Force Warrior, greater dispersal of troops and fighting in urban settings and on non-linearbattlefields, the likelihood of longer evacuation times for combat casualties is anticipated As a consequence of theseconditions and the logistic limitations of weight and cube, fluid resuscitation research within the Army’s Combat CasualtyCare Research Program has focused to investigate limited- or small-volume fluid resuscitation strategies including permissivehypotension, in far-forward areas for the treatment of severe hemorrhage The ultimate goals are to improve battlefield survivaland to reduce or prevent early and late deleterious sequelae in the injured soldier For the military the concept of hypotensiveresuscitation, or fluid resuscitation to a blood pressure below pre-hemorrhage levels currently seems to be a rational approach

to compensate for the limited amount of fluid available on the battlefield to treat casualties, and to minimize the chance forrebleeding from penetrating injuries In addition studies in experimental animals have suggested that hypotensiveresuscitation may improve survival from an uncontrolled hemorrhage (Capone et al 1995; Stern et al 2001)

DTIC

Casualties; Colloids; Combat; Genetics; Hemorrhages; Hypotension; Resuscitation; Swine; Transferring

20050173495 Emory Univ., Atlanta, GA USA

Accelerated Tumor Cell Death by Angiogenic Modifiers

Chung, Leland W.; Aug 2004; 87 pp.; In English

Because of the potential synergistic interaction between an anti-angiogenic aminosterol, squalamine, and other angiogenicmodifiers such as vascular endothelial growth factor (VEGF) and cytokines that may be released during intermittent androgenwithdrawal therapy, we tested extensively the interaction between squalamine and VEGF for an enhanced cytotoxicity tohuman prostate cancer cells in vitro and xenografts tumor models in vivo While in vitro synergistic interaction wasdemonstrated specifically in human prostate cancer cell lines containing a functional androgen receptor, we encountereddifficulty in demonstrating such synergism in vivo for the reason that severe toxicity was noted when VEGF was delivered

as an Ad-CMV-TK vector For this reason, we explored the other possible synergistic interaction between squalamine andcastration Results and Discussion: Squalamine is highly synergistic to castration-induced endothelial destruction whenapplied at the time of castration We noted VEGF receptor, flt-1 and integrin profile (e.g alpha 6 Beta 4) can predictsqualamine response Prostate cancer cells lacking the expression of these markers may be less responsive to the synergisticinteraction between squalamine and castration We are currently assessing the possible interaction between squalamine andVEGF and squalamine and androgen status of the cell culture and in animals subjected to castration to evaluate if synergismmay exist particularly against the growth of endothelial cells

DTIC

Angiogenesis; Cardiovascular System; Cells (Biology); Death; Endothelium; Hormones; Males; Tumors

20050173496 Lady David Inst., Montreal, Quebec Canada

Engineered Autologous Stromal Cells for the Delivery of Kringle 5, a Potent Endothelial Cell Specific Inhibitor, for Anti-Angiogenic Breast Cancer Therapy

Perri, Sabrina R.; Aug 2004; 10 pp.; In English

Glioblastoma multiforme is one of the most highly vascularized tumors in humans Therefore, the development of a potentantiangiogenic gene therapy strategy for brain cancer represents an attractive alternative to existing therapeutic interventionsand circumvents the existing pitfalls associated with direct recombinant antiangiogenic protein delivery Several potentinhibitors of the angiogenic process are known Amongst them, angiostatin, is a cleavage product of human plasminogen

Trang 30

encompassing the first four N-terminal kringle structures Of particular interest is the fifth kringle (KS) of plasminogen thathas been found to enhance the angiostatic potency of angiostatin We propose that the KS domain may serve as a potentangiostatic agent on its own and that it may act as a usefully therapeutic transgene within a cancer gene therapy strategy Totest this hypothesis, we have developed a KS expressing retroviral vector and have characterized the angiostatic activity ofthe de novo produced KS peptide in vitro and tested its efficacy in vivo using an orthotopic brain cancer model Uponintracerebral implantation of lO% U87-GFP (n=S) and U87-KS-GFP (n=S) glioma cells in nude mice, hematoxylin andeosin-stained brain timue sections reveal that U87-K-GFP-implanted mice possess significantly reduced tumor volumes ascompared to the mock implanted mice 32 days post-implantation This evidence suggests that soluble KS peptide holdspromise as an attractive antiangiogenic therapeutic agent within a cancer gene therapy setting.

DTIC

Angiogenesis; Blood Cells; Breast; Cancer; Inhibitors; Mammary Glands; Therapy

20050173498 Wake Forest Univ., Winston-Salem, NC USA

Gene Targeting in Normal Human Breast Epithelial Cells

Thorburn, Andrew M.; Dec 2004; 6 pp.; In English

This exploration grant was to test if it is possible to achieve efficient homologous recombination and gene targeting inimmortalized but otherwise normal human breast epithelial cells Although gene targeting has been achieved in somatic humancells using transfected targeting vectors, the efficiency of this process is very low necessitating the isolation and analysis ofmany thousands of cell clones before a targeted allele can be identified Such approaches are impractical with normal humanbreast cells We tested if the adoption of a different delivery method, needle microinjection, resulted in more efficienthomologous recombination such that targeted clones could be identified after screening fewer colonies Although we obtainedantibiotic resistant clones, we have been unable to identify any clones with targeted alleles We conclude that our idea wasincorrect and that this approach will not be practically feasible without further modification

DTIC

Breast

20050173500 Alberta Univ., Edmonton, Alberta Canada

Examining the Effects of Exercise Training on Tumor Response to Anthracycline-Based Chemotherapy

Jones, Lee W.; Aug 2004; 16 pp.; In English

The purpose of this study is to examine the effects of exercise training on tumor response to anthracycline-basedchemotherapy Eighty athymic Fischer 344 mice will be purchased at 21 days and at 26 days of age, MDA-MB-231 carcinomacells (3x10EXP 6 cells prepared from donor tumors) will be subcutaneously implanted into the right flank of all animals At

40 days of age, animals will be randomly assigned to one of four groups: (i) exercise alone (n=20), (ii) doxorubicin alone(n=20), (iii) exercise plus doxorubicin (n=20), and (iv) control (n=20) Animals assigned to doxorubicin alone and exerciseplus doxorubicin will receive intravenous injections of doxorubicin at 5mg/kg every 7 days The exercise group will beprogressively trained to run at 22m/min at 0% grade for 45 minutes 5 days/week for 8 weeks Forty eight hours after the finalexercise session, all experimental animals will be sacrificed via carbon dioxide anesthetization and cervical dislocation Theprimary tumor will be surgically removed, weighed and histologically processed The primary outcome will be tumor volumemeasured in two dimensions Secondary outcomes will be tumor growth delay calculated as the number of days for eachindividual animal tumor to reach 1000 cubic mm compared with the control group

DTIC

Chemotherapy; Neoplasms; Physical Exercise; Physiological Effects; Tumors

20050173503 Pittsburgh Univ., Pittsburgh, PA USA

Protein Transduction Based Therapies for Breast Cancer

Robbins, Paul D.; Jul 2004; 9 pp.; In English

We have demonstrated that certain transduction peptides such as 12 lysines and 12 arginines can facilitate internalization

Định dạng
Số trang	60
Dung lượng	276,9 KB