| Development of Triplex-Forming Oligonucleotides to Inhibit Expression of the c-myc Oncogene in Breast Cancer Cells |
APR 2003 |
26 pages |
| Authors:
Eileen M. McGuffie; Carlo V. Catapano; MEDICAL COLL OF SOUTH CAROLINA CHARLESTON
|
 | Triple helix-forming oligonucleotides (TFOs) directed to regulatory sequences in gene promoters can selectively block transcription. We are investigating TFO-mediated reduction of c-myc oncogene expression as a means of decreasing breast tumor growth. We designed a novel parallel/antiparallel TFO (Myc-GTC) that had high binding affinity in vitro, but required modifications for increased stability in cells. To further optimize TFO activity we investigated effects of conjugation with the anthracycline antibiotic daunomycin (Dnm), ... |
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| Treatment Decisions in Localized Prostate Cancer: Patient, Partner and Physician |
APR 2003 |
65 pages |
| Authors:
Katrina Armstrong; PENNSYLVANIA UNIV PHILADELPHIA
|
| "Treatment Decisions in Localized Prostate Cancer: Patient, Partner and Physician," is a project that aims to develop and refine an innovative new model of prostate cancer decision making, that will form the foundation of a research and clinical program to understand, support and improve decision making in prostate cancer. This project is using a cross-sectional survey to explore the role of the patient, partner and physician in treatment decisions and ... |
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| P202 AS A Potential Therapeutic Gene for Breast Cancer |
APR 2003 |
24 pages |
| Authors:
Mien-Chie Hung; M D ANDERSON CANCER CENTER HOUSTON TX
|
| The main goal of this proposal is to study the anti-tumor activity of p202 and its application in a breast cancer model system. Three specific aims are 1) To determine the effects of p202 on the sensitivity of breast cancer cells to anticancer agents; 2) To test the anti-tumor activity of p202 in breast cancer cells using preclinical gene therapy strategies in an orthotopic breast cancer animal model; and 3) ... |
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| The Role of Ca2+ and Calmodulin in Estrogen Receptor Function and Tamoxifen Resistance |
APR 2003 |
14 pages |
| Authors:
David B. Sacks; BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
|
| The purpose of this proposal is to evaluate the participation of Ca2+ and calmodulin in estrogen receptor (ER) function and tamoxifen resistance. The focus is directed towards the interaction between calmodulin and ER in ER signaling, as well as the possible involvement of Ca2+ and calmodulin in tamoxifen resistance. Major findings to date are: (i) calmodulin binds directly to ER and stabilizes the receptor; (ii) calmodulin protects ER from degradation ... |
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| Regulation of the Response to Radiotherapy and Hyperthermia in Prostate Cancer by the 26s Proteasome |
APR 2003 |
184 pages |
| Authors:
William H. McBride; CALIFORNIA UNIV LOS ANGELES
|
| The goal of the project was to evaluate the role of the proteasome in prostate cancer biology and response to heat and radiation therapy. We have shown considerable variation between prostate cancers in their functional proteasome activity. In all cases heat and radiation inhibit activity, and this is accompanied by changes in signal transduction pathways that are regulated through the proteasome. Most notably, NF-kappaB is suppressed by heat and by ... |
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| Identification of Naval Inhibitory Peptides of Protein-Protein Interactions Involved in DNA Repair as Potential Drugs in Breast Cancer Treatment |
APR 2003 |
6 pages |
| Authors:
Lajos Pusztai; M D ANDERSON CANCER CENTER HOUSTON TX
|
| We have completed task #2. Sigma 1 receptor (Sig 1 R) mRNA expression was examined in 49 human breast cancers using cDNA microarrays. The data indicates that Sig 1R mRNA expression is heterogeneous in breast cancer. A subset of tumors (20%) has high levels of expression compared to the median Sig I mRNA expression of the group as a whole. The cellular distribution of Sigma 1 protein was also assessed ... |
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| Diagnostic Systems for Pulsed Electric Field Studies |
APR 2003 |
14 pages |
| Authors:
Karl H. Schoenbach; OLD DOMINION UNIV NORFOLK VA
|
| Experimental and modeling studies have shown that nanosecond electric fields allow us to affect internal structures of biological cells. Electrical diagnostics work with temporal resolution in the sub-nanosecond range is critical for evaluation of such ultrafast pulses for the extension of this new bioelectric technique from presently used electrode application in cell suspensions and tissues, to electromagnetic field interactions using antennas. Experiments are ongoing using the 4 GHz bandwidth oscilloscope ... |
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| Isolation and Analysis of Human Kekkon-Like Molecules, a Family of Potential Inhibitors of ErbB Receptor Tyrosine Kinases |
APR 2003 |
11 pages |
| Authors:
Lutz R. Kockel; HARVARD MEDICAL SCHOOL BOSTON MA BIOPHYSICAL LAB
|
| Identification and characterization of proteins involved in intrinsic negative feedback loops autoregulating the transforming c-ErbB2/EGF Receptor activity in vivo. |
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| P16 Axis in Androgen-Dependent Proliferation of Prostate Cancer Cells |
APR 2003 |
14 pages |
| Authors:
Liang Zhu; ALBERT EINSTEIN COLL OF MEDICINE OF (YESHIVA UNIV) BRONX NY
|
| The purpose of this study is to understand the role of the pl6 growth control axis in androgen dependent proliferation of prostate cancer cells. The pl6 axis contains two tumor suppressors (pl6lnk4a and RB), cyclin D-dependent kinases, and transcription factor E2F. We hypothesized that functions of the pl6 axis can influence androgen-dependence of prostate cancer cells. To test this hypothesis, we proposed to use controlled expression techniques to determine whether ... |
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| Patterns Cancer Prevention Through Induction of Phase 2 Enzymes |
APR 2003 |
139 pages |
| Authors:
James D. Brooks; STANFORD UNIV CA
|
| Virtually all human prostate cancers lose expression of glutathione S-transferase-II, an enzyme that protects against oxidative electrophiles that attack the DNA and result in cancer. Based on this observation, we proposed identifying compounds effective at inducing other carcinogen defense (phase 2) enzymes. During our Phase I Award, we identified sulforaphane as the most potent inducer of carcinogen defenses in the prostate cell. We have characterized global effects of sulforaphane in ... |
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| Role of Chromatin Remodeling by RAD54 in DNA Damage Repair and Homologous Recombination |
APR 2003 |
19 pages |
| Authors:
Mariela Jaskelioff; MASSACHUSETTS UNIV MEDICAL SCHOOL WORCESTER
|
| Chromosomal double-strand breaks (DSBs) can arise from cellular DNA metabolism and from eogenous DNA-damaging agents. Efficient repair of these DSBs is critical for genome stability. Rad54, a member of the SWI2/SNF2 family, is involved in the homology recombination (ER) DNA repair pathway. Rad54 has been shown to physically associate with Rad51, a eukaryotic recombinase that in mammals interacts with tumor suppressors BRCA1 and BRCA2. |
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| A Novel RNA Virus System for Selective Killing of Breast Cancer Cells |
APR 2003 |
26 pages |
| Authors:
Griffith D. Parks; WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF MEDICINE
|
| The goals of this project were to develop a novel method for targeting an SV5 infection to breast cancer cells and to control the virus mediated killing by: 1) engineering SV5 to express an anti-HER-2 single chain antibody in place of the normal HN attachment protein, and 2) to engineer SV5 to express the herpes simplex thymidine kinase. The gene encoding an anti-HER-2 single chain antibody (sFv) linked to HN ... |
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| Community Hospital Telehealth Consortium |
APR 2003 |
15 pages |
| Authors:
Elton L. Williams; SOUTHWEST LOUISIANA HEALTHCARE SYSTEM LAKE CHARLES CHTC TELEMED/LCMH
|
| The Community Hospital Telehealth Consortium is a unique, forward- thinking, community-based healthcare service project organized around 5 not-for- profit community hospitals located throughout Louisiana and Mississippi. The central tenet of the CHTC project is the utilization of TeleHealth technology to improve and expand the opportunity for rural and urban underserved populations to receive quality, affordable health care. The CHTC's goals are to improve quality of and access to health care, ... |
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| Do Perturbed Epithelial-Mesenchymal Interactions Drive Early Stages of Carcinogenesis? |
APR 2003 |
6 pages |
| Authors:
Carlos Sonnenschein; Bryan Toole; TUFTS UNIV BOSTON MA
|
| This application should be considered in the context of the competing theories of carcinogenesis. The first is the somatic mutation theory which is based on two main premises: the first, claims that the default state of cells in metazoa is quiescence, and the second posits that cancer is the result of the multistage process where successive mutations accumulate in a single target cell. Much was learned about genes expression under ... |
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| A Novel Apoptosis Pathway That is Defective in Early Breast Cancer |
APR 2003 |
23 pages |
| Authors:
Andrew M. Thorburn; WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF MEDICINE
|
| This project studies a novel apoptosis pathway that is induced by the death domain of the adapter protein FADD (FADD-DD). This pathway induces apoptosis in normal breast epithelial cells but not in breast cancer cells and the project is to determine why cancer cells are resistant to this apoptosis. In this report, we show that resistance to this apoptosis pathway occurs in response to the oncogene sv4O Large T antigen ... |
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| Bio-Hemostat - Acute Treatment Modality for High Pressure Hemorrhage |
APR 2003 |
24 pages |
| Authors:
Marcus E. Carr Jr.; VIRGINIA COMMONWEALTH UNIV RICHMOND
|
| Bleeding from an artery is difficult to control due to the high pressures found in the arterial system. Hemorrhage is especially problematic in penetrating wounds where the bleeding source may not be apparent. Tourniquets that are routinely used to treat such wounds can cause multiple complications. We are developing a device which, when exposed to aqueous solutions, rapidly generates pressure in a confined space. In this report, we summarize the ... |
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| The Role of Ubiquitin-Mediated Proteolysis of Cyclin D in Breast Cancer |
APR 2003 |
17 pages |
| Authors:
Karen L. Block; TEXAS UNIV HEALTH SCIENCE CENTER AT SANANTONIO
|
| Studies have indicated that cyclin D protein levels are modulated post-transcriptionally by the ubiquitin-mediated protein degradation pathway. The specific E2 and E3 enzymes postulated to target cyclin D for ubiquitination are the ubiquitin conjugating enzyme, CDC34, and the ubiquitin protein ligase called SCF/ring (Skp1, Cullin F-box, ring protein). Our findings indicate that CDC34 is phosphorylated by Casein Kinase 2 (CK2) on five carboxyl-terminal residues. Mutation of these residues of CDC34 ... |
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| Phosphorylation of hRad17 by ATR is Required for Cell Cycle Checkpoint Activation |
APR 2003 |
12 pages |
| Authors:
Sean M. Post; Wen-Hwa Lee; TEXAS UNIV HEALTH SCIENCE CENTER AT SANANTONIO
|
| ATR is protein kinase required for both DNA damage-induced cell cycle checkpoint responses and the DNA replication checkpoint, which prevents mitosis before completion of DNA synthesis. Although ATM and ATR share many substrates, the different phenotypes observed in ATM- and ATR- deficient mice indicate these kinases are not functionally redundant. We have shown that ATR but not ATM phosphorylated human Rad17 on serines 635 and 645 in vitro and in ... |
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| The Role of Sigma Receptor in Breast Cancer |
APR 2003 |
6 pages |
| Authors:
Lajos Pusztai; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Task # 1 of our proposal is to determine the affect of Sigma 1 receptor activity on breast cancer cell growth and tumorigenesis in vitro and in vivo. This work includes assessment of expression of Sigma 1 receptor in established breast cancer cell lines and normal breast epithetial cultures by RT-PCR. We also plan to study the effect of Sigma receptor activation or inhibition on cell proliferation, and apoptosis in ... |
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| Development of a Novel In-Situ Telomere Length Qualification System to Address Suitability of Telomerase Inhibitor Therapy to Breast Cancer Following Corrective Surgery |
APR 2003 |
17 pages |
| Authors:
Nicholas R. Forsyth; Jerry W. Shay; TEXAS UNIV SOUTHWESTERN MEDICAL SCHOOL AT DALLAS
|
| Normal breast epithelial cells undergo progressive telomeric shortening throughout their replicative lifespan culminating in critically short telomeres, which trigger replicative senescence. Breast cancer cells are able to bypass this growth-arrest mechanism through deregulated expression of telomerase, which maintains telomeres above the minimal critical length. Based on this observation the suitability of these tumors to telomerase inhibitors as direct or adjuvant therapy needs to be determined. To do this we have ... |
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| Investigation of the Role of Sialomucin Complex (SCMC) /Muc4, a Unique Intramembranous HER-2/ErbB-2 Ligand, as a Suppressor of Apoptosis |
APR 2003 |
|
| Authors:
George Theodore; MIAMI UNIV FL SCHOOL OF MEDICINE
|
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| FAK Signaling in the Acquisition of a Cancerous Phenotype in Breast Epithelial Cells |
APR 2003 |
142 pages |
| Authors:
Veronica Gabarra-Niecko; Michael D. Schaller; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| As a substrate and binding partner for the Src oncogene, a role for the focal adhesion kinase (FAK) in cancer has been speculated. FAK mediates cellular processes including cell motility, survival, and proliferation. Thus, aberrant FAK signaling could lead to pathological effects, including oncogenesis. FAK is overexpressed in a variety of tumors. We have established a cancer cell model system to study the role of aberrant FAK signaling in human ... |
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| A Novel Method to Screen for Dominant Negative ATM Mutations in Familial Breast Cancer |
APR 2003 |
13 pages |
| Authors:
Kum K. Khanna; George Chenevix-Trench; Sean Grimmond; QUEENSLAND INST OF MEDICAL RESEARCH BRISBANE (AUSTRALIA)
|
| The aim of this proposal is to identify families carrying potentially pathogenic AIM mutations by assaying for ATM kinase activity in cell lines derived from individuals with multiple cases of breast cancer in their family but no pathogenic BRCA or BRCA2 mutation ('BRCAx' families). If pathogenic mutations in AIM are found in these families it will substantiate the role of AIM in breast cancer susceptibility, allow us to characterize the ... |
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| Immunotherapy of Breast Cancer Using Novel Her2/Neu-Based Vaccines |
APR 2003 |
8 pages |
| Authors:
Mary Dominiecki; PENNSYLVANIA UNIV PHILADELPHIA
|
| Current breast cancer therapy consisting of surgery, radiation and chemotherapy, fails in 44,000 women per year. Radiation and chemotherapy can also cause significant side effects. New and improved therapies need to be developed to cure patients who fail other therapies. Recently, Her2/neu has been described as a breast cancer antigen because it is overexpressed on 25-40% of all breast cancers. Her2/neu is only expressed at very low levels on normal ... |
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| Methylation Mediated Repression of Selected Genes in Prostate Cancer |
APR 2003 |
12 pages |
| Authors:
Rakesh Singal; DEPARTMENT OF VETERANS AFFAIRS WASHINGTON DC
|
| The present project is focused on understanding the exact mechanism by which methylation silences gene expression in prostate cancer cell lines. Certain proteins bind preferentially to methylated DNA and these proteins have been shown to repress gene expression. In order to determine which of these protein or proteins interact with methylated genes inside the cells, we plan to use using chromatin immunoprecipitation assay. Two important requirements for this assay include ... |
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| X-Ray Crystallographic Studies on Acetylcholinesterase and Related Enzymes |
APR 2003 |
34 pages |
| Authors:
Joel L. Sussman; Israel Silman; WEIZMANN INST OF SCIENCE REHOVOT (ISRAEL)
|
| The objective of the project was to establish a procedure for designing and producing species- specific protein inhibitors, i.e. chimeras, utilizing the scaffold of the three-finger toxins'. Theoretical analysis of the 3D structure of the chimera of a-neurotoxin and fasciculin IT showed that the loops of fasciculin II grafted onto the core of a-neurotoxin maintain their secondary structure. This supports the feasibility of employing protein engineering, using the three-finger toxin' ... |
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| The Effect of Cancer Chemopreventive Agents on DNA Adduct Formation by the Dietary Prostate Carcinogen PhIP |
APR 2003 |
84 pages |
| Authors:
Kenneth W. Turteltaub; Karen H. Dingley; LAWRENCE LIVERMORE NATIONAL LAB CA
|
| This goal of this proposal was to investigate chemopreventive strategies to reduce the genotoxic effects of the prostate carcinogen 2- amino- 1-methyl-6-phenylimidazo4,5-Bpyridine (PhIP). PhIP is considered to pose a significant prostate cancer risk to humans because it is found in cooked meat and epidemiology studies have linked meat consumption to prostate cancer. Importantly, PhIP causes prostate cancer in rats following high-dose exposures. Our purpose was to use the rat model ... |
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| Is Homeopathy Effective for Hot Flashes and Other Estrogen-Withdrawal Symptoms in Breast Cancer Survivors? A Preliminary Randomized Controlled Trial |
APR 2003 |
56 pages |
| Authors:
Jennifer Jacobs; Raleigh Bowden; Patricia Dawson; SEATTLE UNIV WA
|
| Background-Hot flashes, and other symptoms of estrogen withdrawal, are common in breast cancer survivors, for whom hormone replacement therapy is contraindicated. Homeopathic medicines have been used to treat menopausal symptoms for more than 100 years. Objectives-A pilot study to determine if homeopathy may be effective in improving hot flashes and quality of life in breast cancer survivors with symptoms of estrogen withdrawal. Methods- A randomized double-blind placebo controlled trial of ... |
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| Pleiotrophin Signaling Through PTNR in Breast Cancer |
APR 2003 |
11 pages |
| Authors:
Angers H. Kuo; GEORGE WASHINGTON UNIV MEDICAL CENTER WASHINGTON DC
|
| Angiogenesis, formation of new blood vessels, plays a key role in breast cancer growth by providing a method for hematogenous spread of the tumor, as well as providing nutrients for tumor metastasis. Rational treatment strategies for breast cancer must take into account the molecular mechanisms by which cancer develops, maintain its growth and finally spread to other parts of the body. The pleiotrophin (PTN) signaling pathway is known to be ... |
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| The Role of Dynamin in the Regulation of Signaling by the erbB Family of Receptor Tyrosine Kinases |
APR 2003 |
8 pages |
| Authors:
Megan King; Mark Lemmon; PENNSYLVANIA UNIV PHILADELPHIA
|
| Improper regulation of the level and duration of activated erbB family growth factor receptors at the cell surface can lead to uncontrolled cell proliferation and transformation. The GTPase dynamin is a regulator both of transport of receptors to the plasma membrane and down-regulation of receptors via receptor-mediated endocytosis (RME). The localization of specific dynamin isoforms led us to hypothesize that different dynamin isotypes are involved in the distinct processes of ... |
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| Analysis of Progestin Effects on Hepatocyte Growth Factor Signaling Pathways in Relation to Proliferation and Alveolar Morphogenesis of Normal Mammary Epithelial Cells in Vitro |
APR 2003 |
12 pages |
| Authors:
Kyle T. Smith; MICHIGAN STATE UNIV EAST LANSING
|
| Progestin action in the normal adult mammary gland has a major role in the formation of the alveolar bud structure during development and pregnancy. We have determined that for P-induced proliferation and morphogenesis to occur, the presence of hepatocyte growth factor (HGF) is required. When added alone to mouse primary cultures from adult virgin mice, HGF induces proliferation and a ductal morphology. With the addition of P we observe increased ... |
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| Endothelial Cell-Targeted Adenoviral Vector for Suppressing Breast Tumors |
APR 2003 |
7 pages |
| Authors:
Shuang Huang; SCRIPPS RESEARCH INST LA JOLLA CA
|
| Angiogenesis is essential for the growth and metastasis of solid tumors including breast cancer. In vitro and in vivo experimental models clearly demonstrate that suppressing angiogenesis leads to tumor suppression. The overall goal of this proposal is to develop an adenovirus-based gene therapy approach for suppressing angiogenesis. In the first year of the funding period, we focused our effort on developing the endothelial cell-targeted adenovirus vector. We incorporated five previously ... |
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| Synthesis of Targeted Drugs for Treating Breast Cancer |
APR 2003 |
13 pages |
| Authors:
Jerald C. Hinshaw; UTAH UNIV SALT LAKE CITY
|
| New chemotherapeutic agents are needed for the improved treatment of breast cancer. In this proposal, we disclose a new approach to the design of anti-cancer drugs. Our method is to synthesize new drug conjugates that incorporate: (1) a specific breast cancer cell -targeting component; (2) a rapid cell membrane translocating/ nuclear localization moiety and; (3) the capability to counter multi-drug resistance mediated by P-glycoprotein and related cellular efflux pumps. The ... |
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| Signal Transduction in Prostate Cancer |
APR 2003 |
80 pages |
| Authors:
Charles L. Sawyers; CALIFORNIA UNIV LOS ANGELES
|
| The goal of this Prostate Cancer Center Initiation Award was to examine signal transduction pathways involved in prostate cancer progression, with an eye toward translational research applications. The program had two Projects and a Core Animal Facility. The first project (Dr. Carey) focused on crosstalk between receptor tyrosine kinases and the androgen receptor (AR), using the Her2/neu kinase as a model system. During the funding period we completed preclinical studies ... |
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| Preeclampsia-Associated Hormonal Profiles and Reduced Breast Cancer Risk Among Older Mothers |
APR 2003 |
9 pages |
| Authors:
Mark L. Laudenslager; COLORADO UNIV AT FITZSIMMONS AURORA HEALTH SCIENCES CENTER
|
| Preeclampsia has been linked to reduced breast cancer risk, and this reduction may be especially marked among women who bear their first child later in life. In this ongoing case-control study, we examine the hormonal profiles of older Colorado mothers with and without a history of preeclampsia in their first pregnancies. Subjects are nonpregnant, non-smoking women who completed their first pregnancies at age 30 or older, are currently premenopausal, and ... |
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| Effects of CSK Homologous Kinase Overexpression on HER2/Neu-Mediated Signal Transduction Pathways in Breast Cancer Cells |
APR 2003 |
49 pages |
| Authors:
Radoslaw Zagozdzon; Hava Avraham; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Our proposal aims to investigate in details the potential function of CHK in breast cancer as a signal transducer in the signaling pathway from HER2/ Neu receptor. The studies conducted in the period reported included: 1) the assessment of the effects of CHK on the main signaling pathways (RAFTK-and Akt- mediated) induced by the activation of HER2/Neu receptor, 2) comparison of the effects in vitro of wild-type CHK and mutant ... |
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| Neurotoxicity From Chronic Exposure to Depleted Uranium |
APR 2003 |
9 pages |
| Authors:
Stephen M. Lasley; ILLINOIS UNIV AT CHICAGO
|
| This project is designed to test the hypothesis that chronic exposure to depleted uranium (DU) impairs neuronal processes underlying cognitive function via alterations induced at hippocampal glutamatergic synapses. As prescribed by the Statement of Work, efforts were initiated in year I on Technical Objectives 1 (establishment of chronic exposure protocol) and 2 (defining integrity of hippocampal glutamate release) and are continuing into year 2. Blood and brain tissue are being ... |
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| Mechanistic Studies Investigating the Role of Organophosphate Insecticide Exposure in the Development and Exacerbation of Asthma |
APR 2003 |
13 pages |
| Authors:
Allison D. Fryer; JOHNS HOPKINS UNIV BALTIMORE MD
|
| This grant proposes to determine whether organophosphate insecticides act upon the cholinergic system in the lungs increasing cholinerqic neurotransmission and causing airway hyperresponsiveness, which is characteristic of asthma. Guinea pigs were either treated acutely with a high dose or chronically (7 days) with a low dose of the organophosphate,chlorpyrifos sc. Electrical stimulation of the vagus nerves caused frequency-dependent bronchoconstriction that was significantly potentiated in animals treated with chlorpyrifos. M2 muscarinic ... |
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| Structural Basis for the Pharmacological Rescue of Mutant p53 With Small Molecule Compounds |
APR 2003 |
13 pages |
| Authors:
William C. Ho; PENNSYLVANIA UNIV PHILADELPHIA WISTAR INST
|
| The p53 protein is a tumor suppressor crucial to maintaining genomic integrity. In the event of DNA (damage, p53 is responsible for transcribing genes leading to cell death. A class of mutations which occur in the core domain (102-292) leads to thermodynamic destabilization and inability to bind its cognate DNA sequence. Small molecules which bind to and stabilize mutant p53 core domain have potential to be therapeutically useful. A class ... |
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| TRAIL-Based Radio-Gene Therapy for Prostate Cancer |
APR 2003 |
51 pages |
| Authors:
Jae J. Song; PITTSBURGH UNIV PA
|
| We employed a glucose oxidase (GOD) to deplete glucose in the tumor. TRAIL cytotoxicity is potentiated in the presence of GOD. In vitro and in vivo studies have demonstrated that GOD has potent tumoricidal activity. Hydrogen peroxide produced by GOD is effective in preventing tumor growth, and its effect can be enhanced by hydrogen peroxide decomposition inhibitors such as 3- aminotriazole. Moreover, by comparison to normal cells, tumor cells are ... |
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| A High Resolution Clinical PET With Breast and Whole Body Transfigurations |
APR 2003 |
111 pages |
| Authors:
Wai-Hoi Wong; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Despite advances in the last decade, the radiographic diagnosis of breast cancer remains uncertain. Of the annual 600,000 cases referred for biopsy by mammograms each year, 400,000 are unnecessary, costing $2 billion annually. The diagnosis of breast cancer in young women and women with silicone implants continues to be difficult. Accurate detection of small breast tumors (2-3 mm) is still to be achieved. Positron emission tomography (PET) has the potential ... |
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| Structural Studies of the BRCA1-Associated Human SWI/SNF Complex |
APR 2003 |
11 pages |
| Authors:
Marc Holbert; PENNSYLVANIA UNIV PHILADELPHIA WISTAR INST
|
| Mutations in the tumor suppressor gene, BRCA 1 account for 45% of families with a high incidence of breast cancer and the majority of families with high incidences of both breast and ovarian cancers. Recent data has shown BRCA1 to be associated to be associated with a human SWI/SNF complex, serving to link breast cancer to chromatin remodeling (3). Current evidence points to the idea that BRCAl works through SWI/SNF; ... |
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| University of New Mexico Undergraduate Breast Cancer Training Program: Pathway to Research Careers |
APR 2003 |
14 pages |
| Authors:
Jeffrey K. Griffith; NEW MEXICO UNIV ALBUQUERQUE HEALTH SCIENCES CENTER
|
| We have established a three-phase training program to motivate talented undergraduate students, especially students from under-represented southwester minorities, to pursue careers in breast cancer research. Phase I provides a well-rounded introduction to the theory and practice of breast cancer research. This phase includes inquiry-based tutorials that integrate key concepts in normal and cancer breast biology; visits to specialized laboratories that utilize state-of-the-art technologies for breast cancer research; structured interactons with ... |
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| In Situ Evaluation of the Role of the Small GTPase Rac3 in Breast Cancer Metastasis |
APR 2003 |
16 pages |
| Authors:
Suranganie F. Dharmawardhane; TEXAS UNIV AT AUSTIN
|
| We have made considerable progress towards testing the proposed hypothesis that the signaling proteins Rac3 and PAK are critical for the initiation of breast cancer metastasis. Stable fluorescent protein-tagged breast cancer cell lines expressing active and inactive forms of Rac3: MDA-MB-43 5 highly metastatic breast cancer cell line expressing dominant negative Rac3 and Hs578t non-metastatic breast cancer cell line expressing dominant active Rac3 have been created. We have analyzed these ... |
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| Neural Mechanisms of Chronic Fatigue Syndrome |
APR 2003 |
4 pages |
| Authors:
Guang H. Yue; CLEVELAND CLINIC FOUNDATION OH
|
| Nearly one million Americans suffer from chronic fatigue syndrome (CFS). More than 15% of Gulf War veterans (GWV) were found to have CFS. The disease significantly reduces work production of civilian patients and combat ability/readiness of US military forces. Increasing scientific evidence suggests that CFS is a biological illness involving pathology of the central nervous system (CNS). However, little is known about how the CNS is affected by CFS. This ... |
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| Evaluation of Novel Agent Which Target Neovasculature of Breast Tumors |
APR 2003 |
89 pages |
| Authors:
Michael G. Rosenblum; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Biological studies examining the development of the vascular tree in normal development and in disease states have identified numerous cytokines and their receptors responsible for triggering and maintaining this process (1-7). Tumor neovascularization is central not only to the growth and development of the primary lesion but appears to be a critical factor in the development and maintenance of metastases (8-12). Clinical studies in bladder cancer (9) have demonstrated a ... |
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| Mechanism of FADD-DN-Induced Apoptosis in Normal Breast Cells |
APR 2003 |
13 pages |
| Authors:
Lance R. Thomas; WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF MEDICINE
|
| Normal cells undergo apoptosis in response to inappropriate growth signals or the lack of overt survival signals. Tumor cells possess defects in apoptosis regulatory pathways and do not undergo apoptosis in these situations. There are two modes of apoptosis - an intrinsic pathway initiated by stress such as DNA damage and an extrinsic pathway resulting from activation of death receptors. Binding of ligand to a death receptor such as Fas, ... |
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| Use of Tele-Technology for Heart Disease Management: Improving Clinical and Economic Outcomes in a Managed Care Population |
APR 2003 |
11 pages |
| Authors:
Blain H. Yoshinobu; HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE ROCKVILLEMD
|
| Use novel tele-technology web services incorporated into business process redesign and disease state management to improve the disease management and outcomes of patients with Diabetes, Hypertension, Hyperlipidemia (risk factors for Heart Disease which is the number one cause of death in the United States per World Health Organization, 1998 statistics). Providers (physicians, nurses, pharmacists, educators) and patients will be tied together through improved automation, knowledge management, and disease management processes ... |
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| Characterisation of Potential Antimicrobial Targets for Tuberculosis. 1. Methionine Adenosyltransferase in Mycobacterium Tuberculosis and M. Smegmatis |
APR 2003 |
|
| Authors:
Bradley J. Berger; Marvin H. Knodel; DEFENCE RESEARCH AND DEVELOPMENT SUFFIELD (ALBERTA)
|
 | Tuberculosis remains a key concern for the Canadian Forces in its overseas deployments. As drug- resistant forms of the disease continue to spread, there is a need to discover and characterize new drug targets in the organism. The enzyme methionine adenosyltransferase (S-adenosylmethionine synthetase), which catalyzes the formation of S-adenosylmethionine from methionine and ATP, has been cloned, expressed, and characterized in Mycobacterium tuberculosis and its common model organism M. Smegmatis. The ... |
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| Collection of Prostate Cancer Families and Mapping Additional Hereditary Prostate Cancer Genes (HPC2, HPC3,...) |
APR 2003 |
121 pages |
| Authors:
William B. Isaacs; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOLOF MEDICINE
|
| Our initial genome wide search for linkage in multiplex prostate cancer families implicated 1q24-25 as harboring a major prostate cancer susceptibility gene (HPC1), although there was significant evidence for locus heterogeneity and at least 5 other loci were implicated as the sites of HPC genes. Using families ascertained in Phase I of this project, an additional HPC locus located at Xq27-28 (HPCX) was identified. Furthermore we obtained strong preliminary evidence ... |
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Medicine and Medical Research
