nasa scientific and technical aerospace reports phần 4 potx

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-1
testing 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 significantly
different 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 the
relationship. 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 be
dependant on current rules not requiring a referral for mental health care coupled with no out of pocket expense for care. The
application 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 relatively
little 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, and
flourish as metastatic tumors. We postulate that one potential mechanism by which breast cancer cells may acquire such
abilities is their acquired expression of bone specific proteins that are known to be involved in mediating the activities of the
bone-forming cells in the bone tissue, the - osteoblasts. In this study, we attempted to address the critical question of whether
the 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 established
human breast cancer cell lines and planned to -monitor the ability of those cancer cells to grow in the bone as metastases. A
positive finding from such studies will pave the way for the development of potential therapeutic agents for the treatment of
this 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
Report No.(s): AD-A432230; No Copyright; Avail: Defense Technical Information Center (DTIC)
This thesis proposes that it is possible to create an adjunct to traditional instructor-led training that will reduce training
time and costs and at the same time improve performance using commercial off-the shelf (COTS) software. Motivated by the
lessons learned following the attack on the USS Cole on October 12, 2000 in which 17 sailors were killed and 42 were
wounded, we created a simulator using readily available software in minimal time with zero funding and tested it against small
sample sizes of eventual recipients of the training. The simulator, as part of a blended learning solution, was shown to be as
175
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 and
reduced resources.
DTIC
Computer Programs; Education; Medical Personnel; Medical Services; Multimedia; Pilot Training
20050173142 Duke Univ., Durham, NC USA
A Functional Genomics Approach to Identify Novel Breast Cancer Gene Targets in Yeast
Bennett, Craig; May 2004; 39 pp.; In English

Contract(s)/Grant(s): DAMD17-03-1-0232
Report No.(s): AD-A432231; No Copyright; Avail: CASI;
A03, Hardcopy
We are using the yeast Saccharomyces cerevisiae to identify new cancer gene targets that interact with the tumor
suppressor Brcal. Expression of Ercal in diploid WT yeast leads to prolonged Gi arrest and lethality. We identified from a
collection 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 factors
CCR4 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 physically
interact with Brcal in yeast and human cells. Another transcription factor (YAF9) was IR sensitive and rescued Brcal-induced
lethality when deleted. This deletion strain and 19 others were subsequently isolated from the deletion strain pool. Most of
these deletions (75%) were IR sensitive and hypersensitive to the toxin zymocin which appears to induce DSB damage by
inhibiting transcription. Furthermore, most (85%) of these genes are highly conserved suggesting that the hunan orthologs may
interact 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
Contract(s)/Grant(s): DAMD17-00-1-0238
Report No.(s): AD-A432232; No Copyright; Avail: CASI;
A03, Hardcopy
Purpose: To design dual acting inhibitors that can block the enzyme estrone sulfatase and act as antiestrogens. Scope: The
design and%synthesis of 30 dual inhibitors are proposed. The inhibitors contain 4 different structural core. The synthesized
inhibitors will be tested on their ability to inhibit the enzyme estrone sulfatase and also their abilities to inhibit the growth of
breast cancer cells stimulated by estrone suffate. In addition, selected inhibitors will be tested in vivo using NMU-induced
mammary tumors inrats: Major findings: All thirty of the proposed inhibitors have been synthesized. The inhibitors have been
tested 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 Tamoxifen
sulfamate. 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 have
ever 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 30
degraded unexpectedly Which delay ourin vivo studies. The proposed in vivo study is delayed awaiting the synthesis 9f more
compound 30.
DTIC
Breast; Cancer; Inhibitors; Mammary Glands
20050173145 Naval Postgraduate School, Monterey, CA USA
Agent-Based Simulation of Disease Spread Aboard Ship
Gutierrez, Louis M.; Mar. 2005; 65 pp.; In English; Original contains color illustrations
Report No.(s): AD-A432234; No Copyright; Avail: Defense Technical Information Center (DTIC)
Extreme examples like the Spanish Flu pandemic of 1918 make clear the devastating impact that communicable diseases
can have on military readiness. It is highly desirable to have models and tools that can be used to evaluate the course of a
disease over time. These tools can help assess the effectiveness of strategies employed to contain the outbreak such as
176
constraining movement, wearing protective gloves or masks, closing high traffic areas, etc. Armed with these tools, a medical
practitioner can better assess the right course of action in a time critical situation. The primary difficulty with creating models
and simulations for this purpose is that disease spread depends upon the details of human behavior and environmental
variables 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, his
habits of personal hygiene, etc. It is hypothesized that a software disease simulation can combine agents that mimic human
behavior, a ship specific environment, and disease specific attributes to more accurately model the spread of disease aboard
ship 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
Contract(s)/Grant(s): DAMD17-00-1-0459
Report No.(s): AD-A432239; No Copyright; Avail: CASI;

A10, Hardcopy
The overall goal of this research project is to develop and evaluate a new approach to monitoring of oxygenated
hemoglobin concentration (HbO2) of breast tumors under respiratory interventions using near infrared (NIR) spectroscopy and
imaging techniques. The aims have included (1) to evaluate a single-channel, dual wavelength, NIR, frequency-domain
oximeter 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 in
breast tumors using the 3-channel NIR system, and (4) to study the influence of three interventions on HbO2 and PO2 of the
breast tumors. We have accomplished all of the proposed aims and compared the optical method with concurrent
measurements 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 our
current research development in order to fully characterize static and dynamic heterogeneity of breast tumor vasculature under
therapeutic 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 contains
color illustrations
Contract(s)/Grant(s): Proj-02-4-5X-026
Report No.(s): AD-A432255; No Copyright; Avail: Defense Technical Information Center (DTIC)
Numerous gram-negative bacterial pathogens regulate virulence factor expression by using a cell density mechanism
termed 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 the
signaling molecules N-octanoyl-homoserine lactone and N-decanoyl-homoserine lactone. To determine if QS is involved in
the virulence of B. mallei, we generated mutations in each putative luxIR homologue and tested the pathogenicities of the
derivative 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 the
survival of mice who were aerosolized with 10 to the 4th power CFU (10 50% lethal doses). For the B. mallei transcriptional
regulator 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
Report No.(s): AD-A432257; No Copyright; Avail: Defense Technical Information Center (DTIC)
177
The purpose of this analysis was to examine the costs and benefits associated with continuance of ‘in-house’ radiation
therapy services to eligible beneficiaries at Tripler Army Medical Center (TAMC), as opposed to purchasing services. In
determining the optimal solution for TAMC, three models were developed and used to project, for FY04 through FY10, a
financial analysis using historical data. The analysis indicated purchasing radiation therapy services, i.e., outsourcing this care
would produce a cost avoidance of $442,683 to $604, 619, depending upon model comparison. However, the financial data
alone is insufficient to determine the optimal solution. Qualitative factors were analyzed using a relative values decision
matrix. Evaluation criteria consisted of cost, access, perceived quality, measurable quality, and political views. These criteria
were ranked and weighted. A threats, opportunities, weaknesses, and strengths matrix was then used to establish the strategic
direction. Based on the results of this analysis, it is recommended that TAMC continue to provide radiation therapy services
in-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
Report No.(s): AD-A432280; No Copyright; Avail: Defense Technical Information Center (DTIC)
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 growing
diabetic population. One of the major complications of diabetes is diabetic retinopathy, which eventually causes blindness. The
effects of diabetic retinopathy can be limited if early and effective treatment is provided. The key to early intervention is an
annual 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’s
pupils to be dilated, the films obtained and sent for review by an ophthalmologist during their routine primary care visit. This
decreases the hassle factor for the patient, it frees up ophthalmology clinic visits held for routine diabetic eye exams, and best
utilizes 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
Report No.(s): AD-A432290; No Copyright; Avail: CASI;
A05, Hardcopy
The MHS serves approximately 8.6 million eligible beneficiaries, including active-duty military personnel and their
family members (dependents), retired military personnel and their dependents, and surviving dependents of deceased military
personnel. TRICARE, the program that administers health care for the DoD, includes a pharmacy benefit that provides
coverage 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 were
not always available at MTFs because of formulary restrictions. As of FY 2001, DoD introduced a new program for elderly
military retirees and their dependents, entitled TRICARE Senior Rx (TSRx). TSRx beneficiaries can now fill their
prescriptions 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 chronic
conditions. Although it cannot dispense a few drugs, such as atorvastatin, without proof of medical necessity the
overwhelming 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)
178

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
Report No.(s): AD-A432298; No Copyright; Avail: CASI;
A05, Hardcopy
The military health system (MHS) has approximately 8.6 million eligible beneficiaries, including active-duty military
personnel and their family members, retired military personnel and their family members, and surviving family members of
deceased military personnel. In 2002, the Department of Defense (DoD) spent about $3 billion on outpatient pharmacy
benefits. Like the private health care sector, the MHS has experienced a rapid growth in pharmaceutical expenditures. At the
request 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 the
National 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 a
Uniform Formulary (UF), the DoD is considering moving from a two-tiered copayment system to a three-tiered copayment
system, which will increase the copayment for some classes and brands of medications. It is hoped that this move will give
providers (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 how
beneficiaries 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
Report No.(s): AD-A432379; No Copyright; Avail: Defense Technical Information Center (DTIC)
The purpose of this Graduate Management Project (GMP) was to develop a validated survey instrument to gather crucial
feedback 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 to
assure validity in the initial design of this tool. After a thorough literature review, an initial template was developed with
assistance from the Executive Officer (XO) and another instructor assisted in staffing this tool through the ATTC. The second
phase was to have the Survey Administrator, AMEDD C&S, automate and modify the survey to comply with Center and
School training feedback objectives and the Army Surgeon General’s Balanced Scorecard. Finally, the tool went through a
second audit conducted by the ATTC and was piloted for content through the 801st FST at Fort Campbell. The objective of
developing a solid instrument for the ATTC was completed during the course of this project. Ultimately, utilizing this tool to
gather 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
Contract(s)/Grant(s): DAMD17-00-1-0525
Report No.(s): AD-A432401; No Copyright; Avail: CASI;
A03, Hardcopy
Mucin glycoproteins are highly expressed by many tumors, reduce normal cell-cell and cell-extracellular matrix adhesion
and protect cancer cells from attack by the immune system. Mucin expression not only increases, but also changes from a
restricted pattern of apical expression to a general distribution over the entire cell surface. In this regard, conversion of prostate
epithelium from a highly-organized, growth-controlled phenotype to a highly proliferative, metastatic phenotype is associated
with loss of cell polarity. Very few studies been performed on mucin expression by prostate cancer cells. MUC1 is a large
molecular weight, type I transmembrane mucin glycoprotein expressed by normal and malignant prostate epithelium. High
179
level cell surface expression, reported immunosupressive activities of its released ectodomain, and antiadhesive properties all
contribute to this mucin’s ability to protect and promote tumor cell growth and survival. Recent observations using human
breast cancer cell lines indicate that MUC1 can associate with the intracellular signal transducing molecules, beta-catenin and
GRB-2. Recent studies from the PI’s lab demonstrate that cytokines, including interferon-gamma, markedly stimulate MUC1
gene expression. Primary prostate tumors are often found in the vicinity of cytokine producing cells, and commonly

metastasize 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
Contract(s)/Grant(s): DAMD17-03-1-0752
Report No.(s): AD-A432403; No Copyright; Avail: CASI;
A03, Hardcopy
The overall objective of this proposal is to develop cyclic RGD peptide conjugated biocompatible quantum dot
nanoparticles 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 fluorescent
properties of the QDs significantly; and 2) the QD-based breast cancer angiogenesis probes are specific enough to recognize
the integrin receptor and bright enough for effective detection in preclinical animal models. Specific Aim 1: to prepare
water-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 organic
dyes for long-term, multi-target and highly sensitive imaging, however, the current surface coating techniques do not offer
enough stability of QDs in biological medium. On the other hand, NIR fluorescent dyes labeled RGD peptides demonstrated
highly sensitive and semi-quantitative NIR fluorescence images for tumor detection in preclinical xenograft models. This
non-invasive optical imaging approach provides the opportunity for rapid and cost-effective studies before more costly
radionuclide-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
Contract(s)/Grant(s): DAMD17-02-1-0108
Report No.(s): AD-A432404; No Copyright; Avail: CASI;
A05, Hardcopy

The spread of prostate cancer (CaP) to bone causes morbidity and death, yet interactions between CaP cells and bone are
poorly 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 whether
p53 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-incompetent
mice to analyze their ability to form tumors and to spread to the bone. Results/ Progress: p53-mutant CaP cells modulated
osteoclastogenesis and affected osteoblast proliferation; different p53 mutations showed differentiation stage-dependent
effects. Osteoblasts also stimulated the growth of p53 mutant CaP cells, suggesting that osteoblast-CaP interactions lead to new
bone formation and allow CaP to establish in bone. When implanted in mice, some p53 mutant CaP cells inhibited
angiogenesis, and were cytotoxic to bone marrow derived endothelial cells in vitro. We aim to identify the molecules
responsible 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
Contract(s)/Grant(s): DAMD17-02-1-0360
Report No.(s): AD-A432411; No Copyright; Avail: CASI;
A03, Hardcopy
180
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 biological
functions 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 novel
protein, named CLB2 in this study, as a major physiological partner of BRCA2. I discovered that CLB2 is a chromatin bound
protein 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 part
through 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
Contract(s)/Grant(s): DAMD17-01-1-0183
Report No.(s): AD-A432413; No Copyright; Avail: CASI;
A03, Hardcopy
We identified a novel transcription factor, LMO4, which is highly expressed in breast epithelial cells during mid-
pregnancy when these cells are proliferating and invading the stroma. Since previous members of the LIM only (LMO) gene
family are oncogenes, we hypothesized that LMO4 may play roles in mammary gland development and cancer. We have now
shown that expression of LMO4 correlates with proliferation, and in transgenic mice we shrewd that dominant-negative
LMO4 inhibits lobuloalveolar development, demonstrating that LMO4 plays roles in proliferation and/or invasion of breast
epithelial cells. Because these cellular features are associated with breast carcinogenesis and because LMO4 is overexpressed
in a subset of breast cancers, our studies implicate LMO4 as a possible oncogene in breast cancer. In addition, we found that
the LMO4 gene is activated by the Her2/Neu receptor in breast cancer cells, providing further linkage to breast cancer. In
biochemical assays we showed that LMO4 may act by associating with the GATA3 transcription factor, also expressed in
mammary epithelial cells. We have also created stable breast cancer cell lines in which we can induce expression of LMO4
and 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
Contract(s)/Grant(s): DAMD17-03-1-0154
Report No.(s): AD-A432418; No Copyright; Avail: CASI;
A06, Hardcopy
PURPOSE: To examine the topographical variation in expression levels of genes associated with prostate cancer, telomere
dysfunction and/or chromosomal instability. SCOPE: To show that telomere erosion observed in prostatic epithelium may

involve 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 more
susceptible to undergo chromosome end-fusion thus triggering genomic instability. Our initial progress showed that loss of
telomere length occurred in preneoplastic HPIN lesions that were located close to small, localized microfoci of newly
diagnosed prostate cancer. We have optimized whole genome and RNA amplification techniques and shown that there is high
fidelity and reproducibility of dissected amplified PCR product. RESULTS: The first phase of gene expression profiling in
HPIN, and cancer foci using repair/damage response array has been successfully performed. We are developing topographical
maps of telomere bass, genomic instability and concomitant changes in gene expression. SIGNIFICANCE: These results will
form the first direct link between telomere-dependent alteration, DNA repair and damage response signaling in prostate cancer.
DTIC
Cancer; Chromosomes; Deoxyribonucleic Acid; Prostate Gland
181
20050173226 Royal Prince Alfred Hospital, Camperdown, Australia
Epigenetic Inheritance of Breast Cancer
Clark, Susan J.; Sep. 2004; 20 pp.; In English
Contract(s)/Grant(s): DAMD17-03-1-0642
Report No.(s): AD-A432420; No Copyright; Avail: CASI;
A03, Hardcopy
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 the
hereditary breast cancer. We developed a high-throughput sensitive real-time methylation assay that allowed us to screen for
BRCA1 methylated DNA. We used this assay to screen for BRCA1 methylation from DNA isolated from archival blood and
biopsy 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
Report No.(s): AD-A432429; No Copyright; Avail: CASI;
A07, Hardcopy
The overall goal of this project is to probe the CTL - tumor cell interaction by generating scFv probes that are able to
recognize the HLA-A*0201-HER-2/neu369-377 peptide complex. In the 12 month period covered by this report, I have
successfully generated HLA-A*0201-HER-2/neu369-377 complexes, and have isolated two scFv fragment clones that
recognize 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 the
availability of a wide panel of mAb to these antigens that several investigators in our laboratory, including myself, have
developed and characterized. Collectively, the results we have obtained strongly support our future analysis to correlate the
expression 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 to
contribute to our knowledge of the variables that influence the levels of HLA class I antigen-TAA derived peptide complex
expression 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
Contract(s)/Grant(s): DAMD17-02-1-0553
Report No.(s): AD-A432434; No Copyright; Avail: CASI;
A03, Hardcopy
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 sensitivity
and specificity, and it is predictive of breast cancer risk. Thus, the use of HRT, through its effect on breast density, may
compromise the well-established reduction in mortality gained by mammographic screening. However, not all women on HRT
will experience an increase in breast density. We propose a novel hypothesis to explain in part the individual variability in
breast density seen among women on HRT: differences in breast density are associated with differences in estrogen

metabolism, and this association may be attenuated by individual factors such as body mass index and HRT regimen. Our work
and the work of others provide compelling evidence to support this hypothesis. To date 50 cases and 180 healthy
postmenopausal women have been enrolled in this study.
DTIC
Breast; Cancer; Determinants; Hormones; Mammary Glands
182
20050173235 Hawaii Univ., Honolulu, HI USA
Genetic Plymorphisms, Estrogens, and Breast Density
Maskarinec, Gertraud; Jan. 2005; 48 pp.; In English
Contract(s)/Grant(s): DAMD17-00-1-0281
Report No.(s): AD-A432441; No Copyright; Avail: CASI;
A03, Hardcopy
This study investigated the association between genetic polymorphisms in hormone producing and metabolizing enzymes
and several markers of breast cancer risk among women of different ethnic background. The specific aims were to analyze the
relation 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 the
association of breast density with estrogen levels. Mammograms for 328 women were assessed for breast density using a
computer-assisted method. The genes were analyzed for polymorphisms using PCR/RFLP methods and estrogens and their
metabolites were measured by radioimmunoassay. We found that women carrying the COMT and CYP1A2 variant alleles had
lower mammographic densities than women carrying the common alleles. The CYP1A2 C allele was also significantly
associated 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 their
metabolites 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

Contract(s)/Grant(s): DAMD17-01-1-0056
Report No.(s): AD-A432448; No Copyright; Avail: CASI;
A06, Hardcopy
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 nonlinear
mixed effect modeling framework with likelihood based estimation incorporating the EM algorithm. The model was tested
statistically using a subset of 35 patients with relatively homogenous tumor and treatment characteristics. The research
described in this report successfully applied the methodology to a larger population of men (\g600 patients) representing all
stages 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 estimating
mixture 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
Contract(s)/Grant(s): DAMD17-03-1-0548
Report No.(s): AD-A432449; No Copyright; Avail: CASI;
A02, Hardcopy
Cancer cells have long been known to express glycosylation patterns that are different from those found on normal cells
from the same tissue. Many tumor-specific carbohydrate antigens possess the monosaccharide sialic acid, and as a
consequence, many tumor cells express high levels of sialic acid compared to normal cells. Thus, any agent that targets sialic
acid 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. The
unnatural 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 the

azide can be covalently reacted on the cell surface with triarylphosphine probes in vivo. The objective of this project is to
183
develop a novel breast cancer targeting method that exploits the selective chemical reactivity of unnatural sialic acids for
delivery 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
Contract(s)/Grant(s): DAMD17-99-1-9461
Report No.(s): AD-A432451; No Copyright; Avail: CASI;
A03, Hardcopy
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 and
carcinogenic processes have identified a number of specific genes and processes that are dysregulated in breast cancer. This
means that research on breast cancer has finally advanced to the stage where a concentrated effort in translational research will
yield great strides in detection, diagnosis, and treatment. The Molecular Medicine graduate training program at Yale was
recently developed to address these issues. This program was developed to offer an interdisciplinary course of study that will
foster an integrated view of disease, built upon a rigorous foundation of basic sciences. The emphasis on disease mechanisms
and translational research is unique to Molecular Medicine, and distinguishes it from other pre-doctoral programs at Yale. The
Predoctoral 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 training
experience 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
Contract(s)/Grant(s): DAMD17-99-1-9264

Report No.(s): AD-A432452; No Copyright; Avail: CASI;
A03, Hardcopy
With the continuous funding from the US army/DOD (with an one-year no extension cost), the training program on breast
cancer research at MDACC has had a successful fifth year. The training program has supported three pre-doctoral trainees last
year and total 16 predoctoral and 16 postdoctoral fellows were supported by the program during the funding period. Each
trainee has made notable progress as evidenced by publications and presentations at national meetings. Significant strides have
been made within the scope of the original specific aims in the following research areas: therapeutic approaches for breast
cancer through regulation of oncogene and tumor suppressor gene expression, and control of signal transduction and
apoptosis; use of animals to understand the biology of breast cancer and to provide models for preclinical therapeutic and
preventive 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
Contract(s)/Grant(s): DAMD17-02-1-0385
Report No.(s): AD-A432454; No Copyright; Avail: CASI;
A02, Hardcopy
Ipl1p is the budding yeast member of the highly conserved Ipl1/Aurora kinase family. Ipl1p is required for chromosome
biorientation and the spindle checkpoint. Previous work done in the Biggins laboratory uncovered new functions for Ipl1p in
spindle 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
184
is phosphorylated by Ipl1p in vitro and is a phospho-protein in vivo. Mutating one of the Ipl1p consensus sites in Kip3p
generates a spindle disassembly delay similar to ipl1 and kip3DELTA mutants. We are currently testing whether the Kip3p is
phosphorylated 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
Report No.(s): AD-A432458; No Copyright; Avail: Defense Technical Information Center (DTIC)
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 of
Prime patients to the contractor, determine if those losses are appropriate, and recommend possible solutions and better
business practices. The study analyzed data involving a five-step process that includes evaluating resource allocation and
productivity, 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 should
also continue with the revised referral / disengagement process currently in place and continue to provide education and
training to primary care providers. Through analysis of in-house and network costs, 13 procedures and diagnoses were
identified that should be either performed in-house or referred to the network that result in a cost savings to the GI clinic of
over $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
Contract(s)/Grant(s): DAMD17-00-2-0015
Report No.(s): AD-A432463; No Copyright; Avail: CASI;
A03, Hardcopy
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 in
combination for 3 weeks as compared with untreated controls. The work during this reporting period included analysis of
locomotor activity (LA) and autonomic control of heart rate (HR), as well as the metabolism of acetylcholine (ACh) and

choline (Ch), at 2, 4 and 16 weeks after exposure to the ChE inhibitors. HR, derived from electrocardiogram, and LA were
studied by radiotelemetry of animals in their home cages 24 hrs a day, during one week. ChE inhibitors decreased HR and
enhanced 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 other
cholinergic markers, or related to characteristics of the blood-brain barrier were found, but ACh and Ch contents were altered
only at two weeks post-treatment. No treatment-related effects were detected in ACh turnover. In conclusion, changes in the
variables under study were mainly observed 2 weeks after treatment but failed to persist until later intervals. Thus, these
experiments do not support the hypothesis that exposure to low levels of cholinesterase inhibitors could induce persistent or
delayed effects in control of heart rate and locomotion or cholinergic metabolism.
DTIC
Acetyl Compounds; Acetylcholine; Autonomic Nervous System; Choline; Cholinesterase; Dosage; Physiological Effects
20050173245 Duke Univ., Durham, NC USA
Relationships of Stress Exposures to Health in Gulf War Veterans
Fairbank, John A.; Oct. 2004; 30 pp.; In English
Contract(s)/Grant(s): DAMD17-98-1-8662
Report No.(s): AD-A432464; No Copyright; Avail: CASI;
A03, Hardcopy
Despite nearly a decade of research, lack of consensus remains about the precise nature, etiology, and significance of Gulf
185
War veterans’ health concerns. No widely accepted case definition for Gulf War illness exists and controversy persists about
whether Gulf War veterans symptoms ‘should be considered primarily a part of a general phenomenon that occurs in every
war or a consequence of events and exposures unique to the Gulf War’ (Steele, 2001, p. 406). In an effort to further elucidate
the nature of ill-health among Gulf War veterans, we conducted a latent class analysis of symptoms reported in the Tenth
Anniversary Gulf War Veterans Health Study, a national population-based survey of U.S. Gulf War veterans. Specifically, we
sought 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, we
sought to examine the functional consequences of specific patterns of ill-health and probable PTSD ten years after the Persian
Gulf 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
Contract(s)/Grant(s): W81XWH-04-1-0403
Report No.(s): AD-A432469; No Copyright; Avail: CASI;
A03, Hardcopy
The U.S. Medicine Institute for Health Studies, a nonprofit entity devoted toward enhancing communication among
federal agencies and between federal agencies and the private sector, conducts forums and smaller roundtable discussions at
which high-level officials engage in frank discussion of issues of current import to federal health programs. During 2004, the
Institute addressed these issues: the value of long-term studies (forum); healthcare for reserve forces (roundtable); mental
health services for veterans (roundtable); and the future beyond the electronic health record (roundtable). Results of those
discussions 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
Contract(s)/Grant(s): DAMD17-02-1-0434
Report No.(s): AD-A432471; No Copyright; Avail: CASI;
A03, Hardcopy
Cryptophycins are a potent, tumor-selective class of tubulin-binding antimitotic anticancer agents with excellent activity
against MDR cancers. For the development of these promising compounds into useful chemotherapeutic agents, detailed
information about the binding domain of the cryptophycins is essential. We plan to map the cryptophycin binding site through
photoaffinity labeling studies. Toward this goal we have prepared ClO azido analogues of cryptophycin-24 and have evaluated
them 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
Report No.(s): AD-A432482; No Copyright; Avail: Defense Technical Information Center (DTIC)
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 and
technology developed from the program into metabolic research and monitoring applications for soldiers. The Diabetes
Technology Society has been a key forum for dissemination of DoD interests and research results, at the annual Fall meetings
and in a Military Metabolic Monitoring section of Diabetes Technology and Therapeutics. Papers feature DoD-supported
research, 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 the
journal (2004-2005). Topics include IGFI monitoring, advanced technology, hyperspectral imaging accelerometry, foot-strike
186
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
Contract(s)/Grant(s): DAMD17-01-2-0047
Report No.(s): AD-A432498; No Copyright; Avail: CASI;
A06, Hardcopy
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 and
molecular biology of anthrax, human cytochrome P45O defenses, inflammatory oxidation, apoptosis, reperfusion injury, organ
failure, and nitric oxide. New techniques have been developed to automatically diagnose ischemia and heart, kidney, and
respiratory failure. STAT science have also developed new techniques to diagnose and image tissue inflammation and necrosis
using 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 and
cancer. In summary, DREAMS-STAT is making better the expected progress toward its goal of improving the care of
battlefield 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
Report No.(s): AD-A432503; No Copyright; Avail: CASI;
A04, Hardcopy
The purpose of this research was to assess the effectiveness of the OHI information collection process in a uniformed
services military treatment facility (MTF). 442 OHI surveys were administered to beneficiaries presenting civilian
prescriptions to the MTF outpatient pharmacy from 01 to 29 February 2004. The average level of OHI present in the sample
analyzed 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 is
used for prescription drug needs. Multiple linear regression results indicated a statistically significant relationship in the
prediction of having OHI, with R2 = .192, F (13, 428) = 7.829, p \h.0001. Further hypothesis tests with hierarchical multiple
regression analyses indicated that all predictor variables made substantive unique contributions to having OHI with the
exceptions 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 party
collections 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
Contract(s)/Grant(s): DAMD17-01-1-0216
Report No.(s): AD-A432519; No Copyright; Avail: CASI;
A02, Hardcopy
We are continually conducting clinical experiments at the UConn Health Center and Hartford Hospital. The statistical
analysis of the first 65 cases (including 8 cases of cancers and 57 cases of benign lesions) shows strong correlation between
the total hemoglobin concentration and malignance. There is about two-fold increase in the total hemoglobin concentration

for cancers compared with the typical values for benign lesions. This agrees with our hypothesis that optically available
parameters can significantly improve the accuracy of breast cancer detection. To further improve the performance of optical
imaging system, we are pursuing the time-resolved method. We have developed a time-resolved diffusive optical tomography
system via a novel spread spectrum approach. A low power (%5 mW) laser diode modulated with pseudo-random bit
sequences replaces the short pulse laser used in conventional time-resolved optical systems, while the time-resolved
187
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-dimensional
scanning 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
Contract(s)/Grant(s): DAMD17-01-1-0180
Report No.(s): AD-A432544; No Copyright; Avail: CASI;
A02, Hardcopy
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 center
with expertise in basic research and the design and regulation of clinical investigation and to form partnerships with the
pharmaceutical industry to facilitate the rapid translation of novel therapeutic approaches to breast cancer. At the time of our
most 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 of
challenges being faced at most academic institutions, over the last two years accrual to clinical trials of patients with cancers
other 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
Contract(s)/Grant(s): DAMD17-01-1-0022
Report No.(s): AD-A432546; No Copyright; Avail: CASI;
A02, Hardcopy
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 become
androgen independent that prove fatal. It appears that a functionally active AR may contribute to the progression of
androgen-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 this
disease. We have proposed to identify the signaling components that regulate AR activity using a novel retrovirus- mediated
genetic system, and to understand the mechanism of how the identified factors control AR activity. To this end, we have
established and optimized our retrovirus-mediated genetic screen approach. The retroviral vectors to be used have been
improved which will allow high-efficiency mutagenesis and ease of manipulation and analysis. We have also made significant
progress towards optimizing our screening strategies and establishing a suitable cell line for the genetic screen. With these
tools in hand, we are in the process of performing the genome wide genetic screen to identify genes that are important for
androgen 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
Contract(s)/Grant(s): DAMD17-03-1-0750
Report No.(s): AD-A432547; No Copyright; Avail: Defense Technical Information Center (DTIC)
The purpose of this study was to evaluate the combined impact of surgery and immunomodulation with low dose cytoxan
and GM-CSF on the development of dendritic cells and the activation of T cells in vivo. MMTV Her2/neu mice, which
188
spontaneously develop mammary tumors were treated with combinations of cytoxan, GM-CSF and surgery. Flow cytometry

was used to evaluate blood (B), lymph nodal tissue (LN), and splenocytes (S) for evidence of monocyte differentiation to
dendritic cells (DC). Both tumor naive mice and mice with spontaneous tumor growth were evaluated. With this study we were
able to identify a subpopulation of monocytic cells with characteristics consistent with partial differentiation to dendritic cells
using the cell surface markers CD11C, MHC II, CD86/CD40, CD80, and Ly6c. While this study was unable to demonstrate
alteration of the cell surface markers of the monocytic cell populations in a manner consistent with dendritic cell differentiation
using GM-CSF or cytoxan, this study suggests that the presence of tumor itself may alter the CD40 and MHC II level in the
spleen 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
Contract(s)/Grant(s): DAMD17-99-1-9247
Report No.(s): AD-A432548; No Copyright; Avail: Defense Technical Information Center (DTIC)
Excessive consumption of dietary fat may enhance the rate of breast cancer metastasis. In addition, it is generally accepted
that the upregulation of endothelial cell adhesion molecules is involved in the formation of blood-borne metastasis. Among
different adhesion molecules, evidence indicates that intracellular adhesion molecule-1 (ICAM-1) may play a critical role in
breast cancer metastatic formation. Our studies have demonstrated that dietary fatty acids can exert highly specific effects on
NF-kB activation and expression of adhesion molecules in human endothelial cells. In addition, we indicated that linoleic acid
induces ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) expression through the activation of NF-kB. More
importantly, 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, the
present 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
Contract(s)/Grant(s): DAMD17-01-1-0088

Report No.(s): AD-A432551; No Copyright; Avail: CASI;
A03, Hardcopy
Androgens are intimately associated with prostate cancer progression. One of the androgen-response genes encodes
calreticulin, 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 and
metastasis of prostate cancer cells in orthotopic and subcutaneous xenograft tumor models and calreticulin expression is
down-regulated in human prostate tumor specimens. Thus, down-regulation of calreticulin in clinical prostate cancer
specimens is an important step in prostate cancer progression. Our observations argue that part of androgen-induced gene
expression 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 have
lectin-like chaperoning activity, is responsible for the suppression of prostate tumor growth. Our results provide strong basis
for 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
Contract(s)/Grant(s): DAMD17-99-1-9233
Report No.(s): AD-A432552; No Copyright; Avail: CASI;
A05, Hardcopy
We identified a novel vitamin D analog, 1 alpha-hydroxy-24 ethyl vitamin D5 (1 alpha(OH)D5) that showed potent
189
growth inhibitory and cell-differentiating actions in breast cancer cells. Based on our findings in vitro and in vivo, we
hypothesized that 1 alpha(OH)D5 (D5), when administered to women with breast cancer, will induce differentiation of
dedifferentiated 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 studies
showed that D5 has no effect on normal breast epithelial cells but induces apoptosis in breast cancer and showed apoptotic
effect 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 studies
showed D5 to have no effect of cell proliferation , cell death, or differentiation markers (casein) in nonmalignant breast

epithelial cells. In 2002-2003, in vitro studies suggested a differential effect of D5 on ER+ vs. ER- cells and that D5’s action
may be mediated, in part, by VDR. Clinical trial protocols were updated for both the UIC IRB and FDA. In 2003-2004, the
clinical 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 been
submitted 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 color
illustrations
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 atypical
pneumophia, Mycaplasma pneumoniae, Chlamydophia pneumoniae, Legionella pneumophila, and Bordetella pertussis in
uncultured patient specimens. These organisms cause similar symptomologies and are often not diagnosed because they are
difficult to identify with classical methods such as culture and serology. Given this, the overall impact of these pathogens on
public 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
20050173283 Naval Health Research Center, San Diego, CA USA
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 color
illustrations
Report No.(s): AD-A432558; NHRC-04-25; No Copyright; Avail: Defense Technical Information Center (DTIC)
Much attention has been given to the impact of deployment upon the health of veterans from the first Gulf War. While
differences in self-reported symptoms have been common, no specific exposures have been implicated. Some have suggested
that stress from deployment is the chief cause for multi-symptom conditions among 1991 Gulf War veterans. We sought to

examine the impact of large military deployments upon hospitalization experience. Hospitalization records from October
1,1988, 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 and
temporal changes. In comparison with Gulf War veterans (n = 455,465), personnel deployed to Southwest Asia after the Gulf
War (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 not
support the theory of a unique illness in 1991 Gulf War veterans.
DTIC
Asia; Bosnia and Herzegovina; Combat; Deployment; Gulfs; Military Personnel; Warfare
190
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
Contract(s)/Grant(s): DAMD17-02-1-0022
Report No.(s): AD-A432559; No Copyright; Avail: CASI;
A03, Hardcopy
Tumor cell resistance to apoptosis and immune attack are obstacles to effective prostate cancer therapy. Androgen
dependent LNCaP prostate cancer cells are sensitive to apoptosis induced by galectin-l, a human lectin that is abundant in
prostate stroma. In contrast, androgen independent LNCaP, DU145 and PC-3 cells are resistant to galectin-l induced death and
express 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 induced
cell death. Galecti-l resistance in androgen independent LNCaP cells correlates with decreased expression of a specific
glycosyltransferase, C2GnT, that creates 0-glycan ligands recognized by galectin-l. Blocking Oglycan elongation by
expressing a competing glycosyltransferase, ST3Gal I, renders LNCaP cells resistant to galectin-l death. Galectin-1 resistant
DU145 and PC-3 cells can kill adherent T cells via cell surface gal-1. Moreover, PC-3 cells secrete a factor that up-regulates
gal-1 expression by endothelial cells, which then can kill adherent T cells. Thus, enhancing galectin-1 prostate cancer cell
death may allow novel therapeutic approaches to manipulate tumor cell glycosylation to overcome tumor cell resistance to
apoptosis and to prevent tumor evasion of the immune response.

DTIC
Cancer; Death; Epithelium; Prostate Gland
20050173285 Naval Health Research Center, San Diego, CA USA
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 contains
color illustrations
Report No.(s): AD-A432561; NHRC-04-19; No Copyright; Avail: Defense Technical Information Center (DTIC)
Since 1999, the Department of the Navy (DON) has conducted an extensive suicide surveillance program, using the DON
Suicide 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 risk
factors. The DONSIR significantly improves the capability of the DON to track and analyze data on completed suicides. It
provides the DON with consistent data that can be compared across both the USN and the USMC. It establishes baselines for
suicide rates and suicide event characteristics that can be used to track trends over time. It also evaluates military-specific
correlates of suicide, which cannot be evaluated using civilian, academic literature. This is the fourth annual report on the
DONSIR. This report presents findings from the first 4 years of data collected since the program was initiated in 1999 and
summarizes 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 the
warfighter, given the current level of available knowledge, using methods and data published in the literature. Several
published equations for estimating the standard resting metabolic rate (RMRS), defined as the metabolic rate in the morning
after an overnight fast, with the subject at rest in a thermoneutral environment in a supine position, were also evaluated. A
series of comparison data sets of individual data from results published in the literature, in which obese subjects and subjects
younger than 18 and older than 55 yrs, were eliminated. A comparison between estimated RMRS and RMRS values from the
comparison data set showed that equations developed by Mifflin and coworkers in 1990 fit the data the best. It was determined

that once inherent differences in the subject populations used to develop and test the equations were considered, that the
equations developed by differences in the subject populations used to develop and test the equations were considered, that the
equations developed by Schofield (1985) for the World Health Organization, provided the best fit to the data. From linear
regression analyses on the comparison data set, it was found that a combination of the estimated lean body mass (computed
191
from weight, age and gender) and gender or the body weight (W, kg) with gender and age fit the data equally well
STANDARD 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
Report No.(s): AD-A432649; No Copyright; Avail: Defense Technical Information Center (DTIC)
The Chief of the Army Reserves LTG James R. Helmly in September 2003 provided a plan that addresses the Army
Reserve Bridge to Transformation and it is officially called the Federal Reserve Restructuring Initiative. The Federal Reserve
Restructuring Initiative is synchronized with the Army’s Transformation Campaign Plan and addresses people readiness and
transformation. 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 Reserve
Component Imperatives are: 1. Reengineer the mobilization process; 2. Transform command and control; 3. Restructure units
into a flexible and adaptable force; 4. Improve human resources staff; 5. Build a rotational-based force; and 6. Improve
individual support to combatant commanders. The purpose of this strategic research project is to focus on the current
transformation guidance review current transformation initiatives and consider the implications of these imperatives on the
health service capabilities in the Army Reserve.
DTIC
Health; Medical Services; Reserves
20050173340 Walter Reed Army Medical Center, Washington, DC USA
Walter ReedArmy 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
Report No.(s): AD-A432678; No Copyright; Avail: Defense Technical Information Center (DTIC)
Walter Reed Army Medical Center (WRAMC) is the premier medical specialty referral center in the USA Department of

Defense (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 military
medical 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 both
Operation Enduring Freedom (GEE) in Afghanistan and Operation Iraqi Freedom (OIE), the two primary operations in the
USA Global War on Terrorism (GWOT) This study was designed to review the composition of initial GWOT inpatient
casualties 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 on
primary diagnosis-related group (DRG) and DRG ‘cost’ were collected for 372 GWOT inpatients admitted to WRAMC in
FY03.
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
Report No.(s): AD-A432681; No Copyright; Avail: Defense Technical Information Center (DTIC)
This study evaluated the patient processing system at the Urgent Care Clinic at MoncriefArmy Community Hospital, Fort
Jackson, SC to assess its timeliness and efficiency. Analysis of patient cycle times at two separate time intervals made it
possible to identify the different time periods and assess the patient’s access to care. A questionnaire was used to evaluate the
effects 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 for
personal treatment experienced rather than access time to receive care. This study underscores the difficulties in identifying
and meeting patient satisfaction and demand.
DTIC
Clinical Medicine; Hospitals; Medical Services; Patients
192
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

Contract(s)/Grant(s): DAMD17-01-1-0753
Report No.(s): AD-A432704; No Copyright; Avail: CASI;
A04, Hardcopy
We previously demonstrated that centrosome amplification correlates with chromosomal instability and loss of
differentiation in breast tumors. The goal of this research is to identify genes important in breast cancer due to their association
with amplified centrosomes, We determined that centrosomes are amplified prior to invasion and amplification is maintained
during 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 lymph
node and estrogen receptor status, chromosomal instability and centrosome amplification, and 3) developed a collaborative
study to look at centrosome amplification, chromosomal instability, and gene expression in a rat model of estrogen-induced
mammary cancer. During this last reporting period we 1) demonstrated that expression of Aurora-A, a centrosome-associated
kinase, correlates to Nottingham Prognostic Index in human breast tumors, 2) demonstrated that estrogen exposure leads to
centrosome 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 induces
centrosome amplification and aneuploidy.
DTIC
Amplification; Breast; Cancer; Chromosomes; Correlation; Estrogens; Gene Expression; Genes; Mammary Glands
20050173360 Academy of Health Sciences (Army), Fort Sam Houston, TX USA
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
Report No.(s): AD-A432710; No Copyright; Avail: Defense Technical Information Center (DTIC)
During fiscal years 2003 and 2004, Evans Army Community Hospital (EACH), Port Carson, Colorado, diligently
prepared 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 echocardiograph
services, which would yield a 36-month return on investment (ROI) of $210,000. Additionally, the potential for an 80 percent
reduction 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 an
annual 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 increase
EACH’s ability to operate within budgetary limits, and more importantly provide the best health care delivery opt ions to all
beneficiaries to whom EACH serves.
DTIC
Cardiology; Hospitals; Medical Services; Radiology
20050173361 Academy of Health Sciences (Army), Fort Sam Houston, TX USA
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
Report No.(s): AD-A432712; No Copyright; Avail: Defense Technical Information Center (DTIC)
Concerns about timely access to health care have driven many military health system (MHS) beneficiaries to question the
way in which the MHS operates. The open access appointment system, based upon a methodology of doing today’s work
today, 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 while
concurrently examining the effect a phased implementation approach had on physician satisfaction, provider continuity, and
appointment availability. Methods: This study is both a qualitative and quantitative, exploratory, descriptive, cross-sectional
study of the requirements needed to implement an open access system and the effect a phased implementation has on clinical
practices. Results: The requirements for implementing an open access system center around controlling appointing practices
within the facility, effective template management, and effective space utilization. Mean levels of provider satisfaction
increased and both provider continuity and appointment wait time improved at statistically significant rates (p\h.01 for each).
193
Conclusions: This study indicates that open access bas benefited KACH, its staff members, and its beneficiary population.
DTIC
Hospitals; Management Systems; Medical Services
20050173364 Academy of Health Sciences (Army), Fort Sam Houston, TX USA
Forecasting Medical Materiel Requirements for Contingency Operations
Moroney, Daniel J.; Apr. 2004; 110 pp.; In English; Original contains color illustrations
Report No.(s): AD-A432719; No Copyright; Avail: Defense Technical Information Center (DTIC)
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 Operation
Iraqi Freedom, this paper identifies how planners forecast requirements, highlights roadblocks to successful forecasting, and

describes tools, models, and procedures for forecasting supplies, both internal and external to the Department of Defense. The
study concludes that effective forecasting of supplies is accomplished through a collaborative team approach between
clinicians, planners, and logisticians. Additionally, planners and logisticians must look beyond authorizations in sets, kits, and
outfits when planning for patient treatment within a theater of operations. Among the various tools discussed, those that base
medical materiel requirements on a time-phased patient driven scenario show the most promise including the Naval Health
Research Center’s Estimating Supplies Program and Resupply Validation Program and the Army Medical Research and
Materiel Command’s Joint Medical Materiel Modeling.
DTIC
Contingency; Forecasting; Logistics Management; Medical Services; Military Operations
20050173366 Academy of Health Sciences (Army), Fort Sam Houston, TX USA
Analyzing the Requirement for a Deployed Warrior Medical Management Center Table of Distribution andAllowances
at Landstuhl Regional Medical Center
Probus, Mark C.; Feb. 2004; 58 pp.; In English; Original contains color illustrations
Report No.(s): AD-A432724; No Copyright; Avail: Defense Technical Information Center (DTIC)
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 and
Allowances organization designed to medically manage evacuees during war. Three separate analyses were conducted to
gather the results. A qualitative historical analysis of the existing Deployed Warrior Medical Management Center at Landstuhl
Regional 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 cost
analysis identified patterns of financial expense, which suggested that evacuation for treatment at Landstuhl Regional Medical
Center was more costly than treatment in the Central Command Theater of operations. The results of these three separate
analyses support the need for a separate Table of Distribution and Allowances organization under Landstuhl Regional Medical
Center dedicated to the management of evacuees during times of war and provide a template for further evaluation and
planning for such an organization.
DTIC
Deployment; Evacuating (Transportation); Medical Equipment; Medical Services; Military Operations
20050173368 Academy of Health Sciences (Army), Fort Sam Houston, TX USA
Breaking the Code to Quality Improvement of Medical Report Translations (A Retrospective Analysis)

Sharpe, Timothy A.; Apr. 2004; 54 pp.; In English
Report No.(s): AD-A432726; No Copyright; Avail: Defense Technical Information Center (DTIC)
Over the past year, the 67th Combat Support Hospital/WMEDDAC has accumulated a backlog of over 4,000 pages of
network provider medical reports awaiting translation. Throughout the Europe Regional Medical Command military medical
treatment facilities have had varying degrees of difficulty with the timely translation of medical reports. However, at 4,000
pages, the 67th CSH/ WMEDDAC has the greatest amount of accumulated medical reports awaiting translation services. The
patient medical record is a vital component to all medical treatment procedures used by clinical staff as both a history and road
map to care. The purpose of this Graduate Management Project (GMP) is to perform a retrospective analysis to objectively
review the medical report translation program and identify obstacles impeding translation services. Additionally, a
194
recommended course of action will be developed to improve translation services and minimize or eliminate medical report
backlogs.
DTIC
Management Systems; Medical Services; Military Personnel; Quality Control; Translating
20050173370 Academy of Health Sciences (Army), Fort Sam Houston, TX USA
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
Report No.(s): AD-A432730; No Copyright; Avail: Defense Technical Information Center (DTIC)
The purpose of this study was to survey DoD physical therapists for their opinions of tDPT programs and compare the
costs 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 are
doctors of physical therapy. A survey of DoD therapists was conducted to describe the attitudes, opinions, and resources
available within the population. Descriptive statistics were computed for the sample. The results were used to create three
COAs 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 as
cost 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

20050173371 Naval Postgraduate School, Monterey, CA USA
Hospital-Based First Responder Mass Prophylaxis Plan
Massey, Mary S.; Mar. 2005; 57 pp.; In English; Original contains color illustrations
Report No.(s): AD-A432731; No Copyright; Avail: Defense Technical Information Center (DTIC)
As the USA improves its collective awareness and emergency preparedness in the face of increased terrorist activity, more
efforts 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 pharmaceutical
caches have elevated the nation s readiness for biological attacks. In order to effectively meet the challenges created by a
bioterrorism attack, its first lines of defense, the first responders, must be rapidly prophylaxed to allow the continuance of their
mission. Many states and localities have tackled the gigantic undertaking of mass prophylaxis plans to provide
chemoprophylaxis to civilians should the need arise. Many cities have developed and tested their plans to provide general
public mass prophylaxis. It is assumed, or briefly mentioned, that the mass prophylaxis of first responders will occur, but few
plans have been developed. The primary objective of this research is to develop, test, and make recommendations for a
straightforward, 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
Report No.(s): AD-A432734; No Copyright; Avail: CASI;
A03, Hardcopy
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), mean
arterial blood pressure (MAP), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were collected for 10 hours
after injury. Following injury, ICP and HR increased above baseline values in all swine with a more pronounced elevation in
animals impacted to a depth of depression of 12 mm. An 11 mm depth of depression was found to most closely mimic

pathological features of human TBI with edema, infiltration of inflammatory cells, pericapillary hemorrhage, and petechial
195
hemorrhages in the white matter. Injury to a depth of depression of 12 mm resulted in cortical laceration obscuring these
features. 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 and
reproducible injury with pathological features similar to human TBI.
DTIC
Biodynamics; Impact Tests
20050173374 Naval Health Research Center, San Diego, CA USA
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 civilian
populations. We describe a methodology to examine respiratory samples that simultaneously identifies broad groups of
bacteria. The process uses electrospray ionization mass spectrometry and base composition analysis of broad-range PCK
amplification 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 of
species-specific primers to housekeeping genes allows strain-typing. This strategy was used to examine samples from military
recruits sickened in a recent Group A streptococcal (GAS) pneumonia outbreak (MMWK 52, 6, p106-109, 2003). The
strain-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 of
patients in an ongoing epidemic, regardless of the etiology, in a time frame not previously achievable.
DTIC
Epidemiology; Infectious Diseases; Microorganisms; Pathogens; Respiratory System; Surveillance
20050173375 Academy of Health Sciences (Army), Fort Sam Houston, TX USA
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
Report No.(s): AD-A432739; No Copyright; Avail: Defense Technical Information Center (DTIC)

A retrospective study was undertaken at the Eisenhower Army Medical Center to investigate the probable cause and
possible solutions to increased waiting room time for patients and prescription errors. The study examined data from a
22-month period (January 2002 through October 2003) . Two multiple variant regression analyses were performed using
average 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 in
pharmacy 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 were
statistically significant. Finally, the paper compared and contrasted the bank teller concept, which is the current business
practice used in the Eisenhower Pharmacy, and other concepts. The use of automation and a system that would mandate call-in
prescription refills were the primary recommendations that resulted from the comparisons. These two methods will most likely
allow the pharmacy to maintain acceptable wait time and produce acceptable levels of prescription errors despite fluctuations
in personnel.
DTIC
Errors; Manpower; Pharmacology; Time Measurement
20050173383 Academy of Health Sciences (Army), Fort Sam Houston, TX USA
Development of a Provider Profiling Tool for Reappointment
Wallace, Melissa A.; Jul. 2004; 62 pp.; In English
Report No.(s): AD-A432761; No Copyright; Avail: CASI;
A04, Hardcopy
Provider profiling is simply measuring a process and/or outcome and comparing it to some defined norm. Profiling has
many uses: utilization management, cost-effectiveness review, meeting access standards, patient satisfaction, outcomes
assessment, population health, etc. Unfortunately, providers have had a very negative reaction to profiling, a tool that can help
them improve outcomes and make their practices more efficient. This paper will explore the reasons for the negative reactions,
196
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 Healthcare
Organizations and to use the tool for ongoing quality improvement. This paper examines the existing profiling system of a
small, rural Army hospital and describes the development of a new database. Given that many Army hospitals are struggling
with the development of an adequate profiling system, this database may prove useful in developing the groundwork to those
facilities.

DTIC
Data Bases; Health; Medical Services; Mission Planning
20050173385 Academy of Health Sciences (Army), Fort Sam Houston, TX USA
Precursor to the TRICARE Next Generation Program
Allen, Tracy L.; Jun. 2004; 131 pp.; In English; Original contains color illustrations
Report No.(s): AD-A432770; No Copyright; Avail: Defense Technical Information Center (DTIC)
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 plans
that fully document their accountability and responsibility in providing care for enrolled beneficiaries. Wilford Hall Medical
Center is located in the San Antonio multiple-service-area-market within the newly designated South region. Within San
Antonio, the Air Force operates Wilford Hall Medical Center, Randolph Clinic, and Brooks City-Base Clinic and the Army
operates BAMC Medical Center, as well as several smaller troop medical clinics. Wilford Hall has been designated as the
multi-market manager and, as such, will be expected to formulate one consolidated business plan for the San Antonio market
area. 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 was
gathered utilizing data gleaned from the TRICARE Operations Center and customized queries from the Composite Health
Care System. Results from a recent data envelopment analysis study were summarized to reveal trends in efficiency levels for
Wilford Hall Medical Center. The paper concludes with the observation that current market management efforts are not
sufficiently bold or far-reaching. Through the focused efforts of a revised Bexar County Community Health Collaborative, San
Antonio could become an ideal community for delivering medical care in a cost effective way, on time and on target, with the
goals 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 illustrations
Contract(s)/Grant(s): DAAD10-01-2-0014
Report No.(s): AD-A432780; No Copyright; Avail: Defense Technical Information Center (DTIC)
Many protein-protein docking algorithms generate numerous possible complex structures with only a few of them

resembling 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 protein
surfaces, except for antibody-antigen complexes, where a very low number of conserved positions is observed at the interface
regions. In the present study we have used this observation to identify putative interacting regions on the surface of interacting
partners. We studies 59 protein complexes, used previously as a benchmark dataset for docking investigations. We computed
conservation indices of residue positions on the surfaces of interacting proteins using available homologous sequences of
interacting proteins using available homologous sequences and used this information to filter out from 55% to 88% of
generated 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, we
relaxed the conformation of the side chains by minimizing the energy with CHARMM. We then calculated the binding free
energy using a generalized Born method and solvent accessible surface area calculations. Using the free energy along with
conservation information and other descriptors used in the literature for ranking docking solutions, such as shape
complementarity 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
197
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
Contract(s)/Grant(s): W81XWH-04-1-0316
Report No.(s): AD-A432781; No Copyright; Avail: Defense Technical Information Center (DTIC)
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 past
year: (1) We have developed models in SCID mice of four different non-angiogenic human breast cancers, and have shown
that 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 been
developed to detect the angiogenic switch when these tumors are still at a microscopic size of 1 mm(sub 3) or less. The most
sensitive and accurate biomarker is the ‘platelet angiogenic profile,’ which determines and quantifies the angiogenic regulatory
proteins being elaborated by a tumor. A second biomarker is a rise in circulating precursor endothelial cells exiting from the

bone marrow and stimulated by a tumor that is undergoing the angiogenic switch. Our translational goal is to treat human
breast cancer, both primary and recurrent, with non-toxic angiogenesis inhibitors guided by biomarkers before tumors can be
anatomically 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
Report No.(s): AD-A432795; No Copyright; Avail: CASI;
A02, Hardcopy
Data indicate a potential role for the Pdr5p P-glycoprotein ATP-binding-cassette (ABC) transporter in mediating
chloroquine sensitivity in S. cervisae. This is consistent with the hypothesis that such a transporter plays a role in mediating
quinoline-drug resistance in P. falciparum, and complements the results of previous studies on the parasite. Additional gene
products also play a major role in mediating chloroquine sensitivity and resistance, apparently through the modulation of
vacuolar 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
Contract(s)/Grant(s): DAMD17-02-1-0443
Report No.(s): AD-A432807; No Copyright; Avail: Defense Technical Information Center (DTIC)
Our laboratories have developed and utilized cultured human mammary epithelial cells (HMEC) to gain information on
the defects in growth control processes that allow finite lifespan HMEC to overcome all senescence barriers, reactivate
telomerase, 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 genetic
and epigenetic changes that permit telomerase reactivation and immortal transformation of finite lifespan HMEC, in a manner
that models changes observed in breast cancers in vivo. Thus far, we have been able to obtain immortalized HMEC using a
combination of two oncogenes (c-myc and ZNF217) with pathological relevance to human breast cancer. Although CGH

analyses of some of these immortal lines did not show any detectable large-scale changes in gene copy numbers, these lines
have all undergone clonal selection, suggesting that unknown stochastic changes, in addition to over-expression of c-myc and
ZNF217, might be necessary for immortalization. We are currently working to identify these stochastic changes. Better
understanding of the underlying molecular changes involved in telomerase reactivation may provide novel prevention
strategies and/or targets for therapeutic intervention in breast cancer pathogenesis.
DTIC
Aging (Biology); Breast; Cancer; Enzymes; Mammary Glands
198