| Improved Breast Cancer Detection Using a Novel In Situ Method to Visualize Clonality |
JUL 1998 |
55 pages |
| Authors:
John Zebala; CHILDREN'S HOSPITAL AND MEDICAL CENTER SEATTLE WA
|
 | We report the successful development of a sensitive clonality assay. The assay is based on a novel method we have developed termed "biolithography" which applies photolithography, a process known in the semiconductor industry, to biologic material. Biolithography uses diazoquinone photoresist and targeted light irradiation to isolate DNA from selected cell populations under direct microscopic visualization with 100% specificity and sensitivity at the limit of ... |
|
| Retinoids and Retinoid Metabolism in Breast Cancer |
JUL 1998 |
22 pages |
| Authors:
Jisun Paik; UNIV OF WASHINGTON SEATTLE
|
| My studies aim to understand vitamin A metabolism in breast tissue, specifically the role of the human 9 cis-retinol dehydrogenase (9cRDH). The 9CRDH gene was cloned from a normalized mammary library by Blaner and colleagues. We studied its expression in two normal human mammary epithelial cell strains (HMECs) and a panel of breast cancer cell lines. mRNA levels were determined by a semi-quantitative, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) strategy. ... |
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| Mammary Gland Ontegeny and Neoplasia in Oxytocin Deficient Mice |
JUL 1998 |
11 pages |
| Authors:
Janet A. Amico; PITTSBURGH UNIV PA
|
| The studies utilize oxytocin "knock-out" and wild type mice (homozygous for the oxytocin gene) to test the hypothesis that diminished oxytocin and the absence of its effect upon the mammary gland, may in part predispose the breast to neoplastic change and its corollary that exposure to oxytocin may be protective. The technical objectives of this proposal as follows. 1) Determine the prevalence of mammary neoplasia in the progeny of MMTV-infected ... |
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| Identification of Surrogate Markers for Estrogen Receptor Action in Breast Cancer Cells |
JUL 1998 |
20 pages |
| Authors:
Julianne M. Galluzzo; DUKE UNIV DURHAM NC
|
| The human estrogen receptor (ER) is a ligand-inducible transcription factor that mediates the biological effects of the steroid hormone estrogen. Different ER ligands can regulate the expression of specific subsets of genes. While "pure' antiestrogens like ICI antagonize ER activity in all contexts, other antiestrogens such as tamoxifen can act as partial agonists in some situations and antagonists in others. Recently a second estrogen receptor (ERb) has been identified, and ... |
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| Breast Cancer Vaccines Based on Dendritic Cells and the Chemokines |
JUL 1998 |
30 pages |
| Authors:
James J. Mule; MICHIGAN UNIV ANN ARBOR
|
| The major objective of this project is to establish a new modality for the treatment of breast cancer that employs the combination of chemokine gene-modified fibroblasts with breast tumor-pulsed dendritic cells (DC) to both recruit and/or concentrate from the periphery low frequency immune reactive T cells as well as to potently stimulate these effector cells once localized at the vaccination site. During the second year of this four-year project, studies ... |
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| Dietary Carcinogens and Breast Cancer |
JUL 1998 |
39 pages |
| Authors:
James W. Gaubatz; UNIVERSITY OF SOUTH ALABAMA MOBILE
|
| We have investigated phase II activation of the cooked meat mutagen 2-hydroxyamino-1-methyl-6-phenyl4,5-Bpyridine (N-OH-PhIP) by cytosolic acetyltransferase, sulfotransferase, and kinase enzymes from human breast tissue. Microsomal fractions of mammary epithelial cells were also examined for prostaglandin II synthetase activation of N-OH-PhIP. The results showed that all four enzymes can participate in activating N-OH-PhIP, thereby inducing PhIP-DNA adducts in human breast cells. However, not all individuals exhibited all four activities, instead each ... |
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| Radiation-Induced Transformation in Human Breast Cells |
JUL 1998 |
24 pages |
| Authors:
Peter J. Thraves; GEORGETOWN UNIV WASHINGTON DC
|
| In this study we have shown that ionizing radiation can transform immortalized/ initiated human breast epithelial cells from a donor with Li- Fraumeni syndrome (LFS) containing a germline mutation in the p53 gene to a malignant phenotype. Exponentially growing human breast cells (HME-50) were irradiated with 2 Gray of gamma radiation with additional doses of 2 Gray delivered at daily intervals to a total dose of 60 Gray. After each ... |
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| P/CAF Function in Transcriptional Activation by Steroid Hormone Receptors and Mammary Cell Proliferation |
JUL 1998 |
54 pages |
| Authors:
Sharon Y. Roth; TEXAS UNIV AT HOUSTON
|
| Inappropriate gene expression and abnormal progression of the cell cycle are intimately linked to oncogenesis and tumor formation. The purpose of this proposal is to examine the role of the PCAF histone acetyltransferase as a co-factor for steroid hormone receptors in the regulation of gene expression. Five specific aims define the scope of our project: 1) to complete the isolation and cloning of mouse PCAF cDNA and genomic sequences 2) ... |
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| A Novel Role for C/EBP in Mammary Development and Breast Cancer |
JUL 1998 |
22 pages |
| Authors:
Cynthia A. Zahnow; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| The objective of this fellowship is to characterize the roles which C/EBP alpha and C/EBP beta play in normal mammary gland development and breast cancer. In general, C/EBP alpha is predominantly expressed at high levels in terminally differentiated, growth arrested cells and the C/EBP beta isoforms, most notably LIP, are expressed at high levels in actively proliferating cells. LIP can act as a dominant negative isoform, which when dimerized with ... |
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| Role of Proteases in Breast Cancer Progression |
JUL 1998 |
122 pages |
| Authors:
Rafael A. Fridman; WAYNE STATE UNIV DETROIT MI
|
| Metastasis is the major cause of death in breast cancer patients. To metastasize, breast cancer cells must degrade extracellular matrices (ECM) using specialized ECM-degrading proteases including matrix metalloproteinases (MMPs) and cathepsins. The purpose of these studies was to understand the mechanisms regulating the expression, cellular localization and activation of MMP-2, MMP-9 and cathepsin B in breast epithelial and fibroblast cells. We have found that breast cancer cells can be induced ... |
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| Estrogens, Microtubules and Aneuploidy: Mechanisms of Mammary Gland Tumorigenesis |
JUL 1998 |
13 pages |
| Authors:
Gregory A. Reed; KANSAS UNIV MEDICAL CENTER KANSAS CITY
|
| The role of estradiol (E2) metabolism in mammary carcinogenesis is being studied in a rat model. Two strains are employed: the ACI is extremely sensitive to E2 carcinogenicity, whereas the Sprague-Dawley is resistant. Characterization of E2 metabolism in liver microsomal preparations showed robust metabolism from 60 micrometerm down to 3 nM. The latter value approximates the physiological concentration of E2. In the micromolar range both strains ... |
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| Novel Cytochrome P45OlBl as a Mammary Cancer Risk Factor |
JUL 1998 |
230 pages |
| Authors:
Colin R. Jefcoate; WISCONSIN UNIV-MADISON
|
| We have recently documented the expression of CYPIAl and CYP1B1, both of which are inducible by many environmental pollutants via the Ah receptor AhR, in human breast cells. The expression of CYP1B1 and CYP1Al has been quantitated in primary human breast luminal and basal epithelial cells LEC and BEC, respectively, in BF, and in estrogen receptor positive and negative (ER+ and ER- , respectively) breast tumor cell lines. ... |
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| A Solid Support Synthesis and Novel Conjugation Methods of Breast Tumor Associated antigen: Toward the Development of Cancer Vaccines |
JUL 1998 |
12 pages |
| Authors:
Hyunjin Kim; Samuel Danishefsky; SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
|
| Immunological study of Globo-H, a breast tumor associated carbohydrate antigen, has been producing promising results. As the demand for the supply of this antigen grows, the efficient production of enough material has become an urgent problem. We have been trying to solve this problem by two approaches: the solid support synthesis of Globo-H, and the development of efficient conjugation methods. For the solid support synthesis, ... |
|
| Regulation of Neu Signaling in Breast Cancer |
JUL 1998 |
36 pages |
| Authors:
Frank Jones; YALE UNIV NEW HAVEN CT SCHOOL OF MEDICINE
|
| ErbB2/neu amplification and overexpression is the most common genetic alteration in breast cancer. As a growth factor receptor and member of the EGFR family, ErbB2 signaling is dependent upon target tissue expression of ErbB2 regulating growth factors and other EGFR family members. To determine the role ErbB2 plays in normal and malignant mammary gland development I examined expression of ErbB2 agonists by ISH during normal development ... |
|
| Suppressor Genes in Breast Cancer |
JUL 1998 |
21 pages |
| Authors:
Robert R. Clarke; GEORGETOWN UNIV WASHINGTON DC
|
| The inactivation of tumor suppressor genes (TSGs) in a variety of human cancers has inspired an intense search for the breast cancer-specific TSGs. The purposes of this proposal are to: (1) clone novel TSGs specific to human breast cancer; (2) examine the alteration of these TSGs in primary breast- tumors; and ultimately (3) identify their characteristics, regulation and function. We have constructed a cDNA library from normal human breast epithelia ... |
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| A Novel Model System to Examine Agents Used in Breast Cancer Therapy |
JUL 1998 |
194 pages |
| Authors:
Jennifer M. Coll; MARYLAND UNIV BALTIMORE
|
| We have isolated a multiprotein complex for DNA synthesis, designated the DNA synthesome. from human breast cancer (MDA MB-468) cells, biopsied human breast tumor tissue and xenografts from nude mice injected with the human breast cancer cell line MCF-7. The breast cell DNA synthesome was shown to fully support the in vitro replication of simian virus 40 (SV40) origin-containing DNA in the presence of the viral large T-antigen. The proteins ... |
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| Xenobiotic Modulation of Human Mammary Epithelial Cell Gap junctional Intercellular Communication and Growth |
JUN 1998 |
24 pages |
| Authors:
Randall J. Ruch; MEDICAL COLL OF OHIO AT TOLEDO
|
| The incidence of breast cancer is increasing dramatically in the United States. Man-made environmental agents such as pesticides, polychlorinated biphenyls (PCBs), phthalate esters, and dioxin have been implicated in this increase. Many xenobiotics such as DDT and PCBs have weak estrogenic activity and may enhance breast cancer formation by an estrogenic effect on breast epithelial cell growth. These agents also inhibit gap junctional intercellular communication ... |
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| Mechanism of Altered Control of Proliferation by Cyclic Amp/Protein Kinase A During Mammary Tumor Progression |
JUN 1998 |
20 pages |
| Authors:
Walter Imagawa; KANSAS UNIV MEDICAL CENTER KANSAS CITY
|
| We examine the hypothesis that alterations in the regulation of growth by prolactin (PRL) and cAMP during mammary tumor progression are related to the ERK and JNK MAP kinase signaling pathways known to be affected by cAMP and pertussis toxin (PT)-sensitive G proteins. Mammary epithelial cells from normal mouse mammary glands were compared to pregnancy-dependent (PDT) and ovarian- independent (OlT) mouse mammary tumors in serum-free, ... |
|
| The Effect of MHC Class II Transactivator (CIITA) on the Growth and Metastasis of Breast Tumors |
JUN 1998 |
16 pages |
| Authors:
Brian Martin; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| CIITA is a recently described protein that up regulates several different genes involved in the MHC class II antigen presentation pathway. I hypothesize that the de novo expression of molecules involved in the MHC class II antigen presentation pathway may render the tumor cells immunogenic and lead to tumor rejection. Also, preliminary data in our lab has revealed that, in addition to its effects on ... |
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| A Novel Role of BCL-2 in the Regulation of Apoptosis Mediated by Remodeling and Turnover of Extracellular Matrix |
JUN 1998 |
24 pages |
| Authors:
Li Gangyong; WAYNE STATE UNIV DETROIT MI SCHOOL OF MEDICINE
|
| The bcl-2 oncogene product is a potent inhibitor of apoptosis induced by a variety of stimuli. Bcl-2 is highly expressed in breast cancer and its expression is related to chemotherapy and radiation therapy resistance. Increasing evidence suggests that remodeling and turnover of extracellular matrix (ECM) play a critical role in the regulation of apoptosis in mammary epithelial cells. In the present study, our purpose is to ... |
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| WNT Proteins in Mammary Epithelial Cell Transformation |
JUN 1998 |
91 pages |
| Authors:
Jan Kitajewski; COLUMBIA UNIV NEW YORK
|
| We have assessed the ability of Wnt-l, Wnt-2, Wnt-3, Wnt-3A, Wnt-4, Wnt-5A, Wnt-5B, Wnt-6, Wnt-7A, and Wnt-7B to transform mammary epithelial cells and found that Wnt-l, Wnt-2, Wnt-3 and Wnt-3A proteins transform mammary epithelial cells; Wnt-7A and Wnt-7B proteins partially transform; and Wnt-4, Wnt-5A, Wnt-5B, and Wnt-6 proteins does not affect mammary epithelial cells. Transformation correlated with Wnt-mediated increases in the cytosolic pool of Beta-catenin. By generating chimeric Wnt proteins ... |
|
| Spatial Distribution of the EGF Receptor System in the Regulation of Breast Epithelial Cell Growth and Organization |
MAY 1998 |
25 pages |
| Authors:
Patrick M. Burke; UTAH UNIV SALT LAKE CITY
|
| 184A1 cells do not form polarized, glandular epithelial structures when plated onto Matrigel, nor do they polarize if plated onto Transwell tissue culture inserts; therefore, 184A1 could not be used to address the primary aim of my proposal: to determine if the loss of receptor system polarization provides a growth advantage, enhances motility, or changes the differentiated state of normal cells. However, because the growth ... |
|
| Tissue Banks and Cell Lines Derived from Patients with a High Risk of Breast Cancer and in situ Disease |
MAY 1998 |
36 pages |
| Authors:
Barry A. Gusterson; ROYAL CANCER HOSPITAL LONDON (UNITED KINGDOM) INST OF CANCER RESEARCH
|
| This project is aimed at establishing bulk cultures of individual epithelial and stromal cells from mastectomy specimens of patients who are carrying genes that predispose them to breast cancer. Epithelial and stromal cells are being conditionally immortalized using an amphotropic retroviral vector transducing the tsA58-U19 SV40-derived construct. These cells are from patients who are mutation carriers of BRCA1, BRCA2, and p53. Samples have been ... |
|
| Using Simulation Software to Improve Operational Efficiency at Region Nine Tricare's Breast Health Referral Center. (A Look at Examination Room Requirements and Staffing Issues) |
APR 1998 |
182 pages |
| Authors:
Karen P. Leahy; ACADEMY OF HEALTH SCIENCES (ARMY) FORT SAM HOUSTON TX HEALTH CARE ADMINISTRATION
|
| As the Military Health System implements managed care concepts throughout all military treatment facilities, administrators and providers are realizing that the care provided within military facilities must be equivalent to the civilian network in terms of quality, patient satisfaction, and cost- effectiveness. Consequently, Naval Medical Center San Diego opened a new Breast Health Center to offer comprehensive care for all region nine beneficiaries. A ... |
|
| Homebox Genes in Normal, Preneoplastic, and Neoplastic Mammary Glands |
JAN 1998 |
22 pages |
| Authors:
Charles W. Daniel; CALIFORNIA UNIV SANTA CRUZ
|
| The overall aim of this project is to improve our understanding of genetic factors regulating the development, differentiation, function, and neoplastic progression of the breast. In 1997 we have investigated the first clearly identified mammary phenotype in homeobox genes, an engineered mutation in mouse Hoxd-10 that causes a deficiency in milk production. We report that Hoxd-10 is strongly expressed in the mammary epithelium in a stage-dependent manner, with highest levels ... |
|
| Episome-Based Gene Therapy Strategy for Treatment of Human Breast Cancer |
JAN 1998 |
47 pages |
| Authors:
Judith Ilan; CASE WESTERN RESERVE UNIV CLEVELAND OH
|
| We have focussed our efforts on investigating the mechanisms by which antisense to type I insulin-like growth factor receptor (IGF-IR) or antisense to transforming growth factor beta (TGFbeta) reduces tumorigenicity in human and murine breast cancer cells. MDA-MB-435S human breast cancer cells expressing antisense IGF-IR enhanced apoptosis in vitro, which could contribute to the reduced tumorigenicity observed in vivo. A dramatic reduction in tumorigenesis and an absence of lung metastasis ... |
|
| Research on Navy-Related Combat Casualty Care Issues, Navy Operational- Related Injuries and Illnesses and Approaches to Enhance Navy-Marine Corps Personnel Combat Performance |
JAN 1998 |
237 pages |
| Authors:
GEO-CENTERS INC NEWTON CENTRE MA
|
| This report summarizes the results of GEO-CENTERS' technical activities for the first option year one of the Naval Medical Research Institute (NMRI) Contract N00014-95-D-0048, Delivery Orders 002 and 003. The delivery orders encompass a variety of scientific studies that are capable of supporting ongoing and projected programs under the cognizance of NMRI; NMRI TOX/DET dayton, OH; NMRI/DET San Antonio, TX; NDRI Great Lakes, IL; the NDRI Detachment Bethesda, MD; the ... |
|
| Prediction of Early Breastfeeding Attrition for First-Time Breastfeeding Mothers |
31 DEC 97 |
94 pages |
| Authors:
Cynithia Furlow-Jeffrey; AIR FORCE INST OF TECH WRIGHT-PATTERSONAFB OH
|
| The purpose of this study was to test the reliability and predictive validity of the Breastfeeding Attrition Prediction Tool (BAPT) when admihistered to first-time breastfeeding mothers, to identify the optimal time for its use, and to determine if responses to the BAPT change between prenatal and postpartum periods. The BAPT was based on the Theory of Planned Behavior that explains behavior as based on constructs of attitude, subjective norm, and ... |
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| Role of Integrin Related Tyrosine Kinases in Growth Control of Normal and Tumorigenic Human Mammary Epithelium |
NOV 1997 |
51 pages |
| Authors:
George Plopper; SCRIPPS RESEARCH INST LA JOLLA CA
|
| We examined the role of the extracellular matrix protein laminin-5 (Ln-5) in static adhesion and migration of normal (HUMEC), immortalized (MCF- 10A) and malignant breast epithelial cells that exhibit different degrees of metastatic potential (MDA-MB-435>MDA-MB-231>MCF). HUMEC, MCF-10A, and MCF-7 cells adhered to purified Ln-5 through the integrin receptor in rapid adhesion assays. While HUMEC and MCF-10A cells remained statically adherent, MCF-7 cells migrated constitutively ... |
|
| New Therapeutic Approaches and Prognostic Assays for Breast Cancer: Radiolabeled Ligands and Antibodies and Quantitative PCR |
NOV 1997 |
54 pages |
| Authors:
Indra Poola; HOWARD UNIV WASHINGTON DC
|
| Breast cancer is a tumor of the mammary gland epithelium affecting about 176,000 women in the western hemisphere and killing about 50,000 people every year in the United States. A substantial body of epidemiological, experimental, and clinical evidence indicates that exposure to the natural hormones, estrogen, progesterone and prolactin, which are important for the normal development and function of the breast tissue, play a major role in the growth of ... |
|
| Breast Cancer Screening by Physical Examination: A Randomized Trial in the Phillipines |
NOV 1997 |
23 pages |
| Authors:
D. M. Parkin; INTERNATIONAL AGENCY FOR RESEARCH ON CANCER LYONS (FRANCE)
|
| Screening of the population in intervention areas continued. By the end of July 1997, 11.9, 97.6 were interviewed and examined. Three thousand were detected positive for a lump and referred for diagnosis to the tumor clinics corresponding to a positivity rate of 2.8%. Compliance with referral was only 21%. Motives of non-compliance were assessed on a sample of 1,000 positive women who did not turn up at the tumour clinics ... |
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| Extracellular Matrix Induced Integrin Signal Transduction and Breast Cancer Invasion |
NOV 1997 |
12 pages |
| Authors:
William C. Powell; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| Breast epithelial cell function is greatly influenced by interactions with the underlying basal lamina. Matrilysin, a matrix metalloproteinase, has previously been shown to be expressed in both adenomas and carcinomas of the human breast. We have tested the hypothesis that cell-ECM interactions regulate the expression of matrilysin in human breast carcinoma cells in vitro. We have used northern analysis and in situ hybridization to determine levels ... |
|
| Role of the EGF-Related Growth Factor Cripto in Murine Mammary Tumorigenesis |
21 OCT 97 |
17 pages |
| Authors:
Michael N. Shen; ROBERT WOOD JOHNSON MEDICAL SCHOOL PISCATAWAY NJ
|
| We are investigating growth factor signaling in the mammary gland through the analysis of Cripto, a gene that is distantly related to epidermal growth factor (EGF). Previous studies have suggested that Cripto may play an autocrine or paracrine role in human breast, colorectal, gastric, and pancreatic carcinomas. To assess whether Cripto plays a role in normal breast development and whether it has a causal role in tumorigenesis, we have generated ... |
|
| The Role of Heparin-Binding EGF-Like Growth Factor in Breast Cancer |
OCT 1997 |
37 pages |
| Authors:
David S. Salomon; NATIONAL INSTITUTES OF HEALTH BETHESDA MD
|
| Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family which binds to and activates the EGF receptor. Its role in breast cancer, however, is unclear. We have studied the mechanism of induction of HB-EGF(by EGF(in the spontaneously immortalized mammary epithelial cell line MCF-10A and in MCF-10A cells that have been transformed with oncogenic Ha-ras. The levels of EGFR, erbB-2 and erbB-3 were ... |
|
| Regulation of Nutrient Transport in Quiescent, Lactating, and NeoplasticMammary Epithelia |
OCT 1997 |
36 pages |
| Authors:
Peter M. Haney; WASHINGTON UNIV ST LOUIS MO
|
| We studied developmental changes in glucose transporter (GT) targeting in mammary gland, a prerequisite for the understanding GT targeting in breast cancer. Previously, we established that GLUT1 is targeted to Golgi during lactation. To understand the regulation of this process, we carried out subcellular fractionation and density gradient centrifugation, Western blotting, and immunofluorescence in mammary glands of mothers whose pups were prematurely weaned. We conclude: (1) There ... |
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| Mechanism of Aromatic Hydrocarbon Induced Mammary Tumorigenesis |
OCT 1997 |
108 pages |
| Authors:
Gail E. Sonenshein; BOSTON UNIV MA
|
| Recent evidence suggests that the rise in breast cancer rates reflects increased exposure to and bioaccumulation of environmental pollutants, such as 7,12-dimethylbenz(a)anthracene (DMBA). Female Sprague-Dawley rats treated with DMBA develop mammary (breast) tumor by about 15 weeks. Mere experiments were proposed to elucidate the roles of the aromatic hydrocarbon (Ah) and estrogen receptors and the c-myc oncogene. Changes in the expression and function of ... |
|
| Treatment of Metastatic Breast Carcinoma Refractory to Doxorubicin with Liposomal-Annamycin |
OCT 1997 |
58 pages |
| Authors:
Roman Perez-Soler; TEXAS UNIV AT HOUSTON
|
| Annamycin is a non-cross resistant doxorubicin analog that is formulated in a liposomal carrier. We have completed a phase I study and initiated a phase II study of liposomal Annamycin in patients with metastatic breast carcinoma. The maximum tolerated dose was 210/mg/m2. The limiting toxicity was myelosuppression. Other toxicities were limited to allergic reactions. No significant cardiotoxicity, alopecia, mucositis, nor gastrointestinal toxicity have ... |
|
| Early Cancer Detection for Filipino American Women |
OCT 1997 |
24 pages |
| Authors:
Magelende R. McBride; NORTHERN CALIFORNIA CANCER CENTER UNIONCITY
|
| The goal of this research is to develop a comprehensive program of interventions designed to increase early breast cancer detection among Filipino American women. This population has been showed to have high rates of late stage breast and cervical cancer. The first step toward increased early detection is identification and measurement of population characteristics related to screening practices and prospective efforts to improve screening rates. A ... |
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| Non-Invasive Detection of Axillary Nodes by Contrast Enhanced Magnetic Resonance Imaging |
OCT 1997 |
15 pages |
| Authors:
Jason A. Koutcher; SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
|
| Previous studies in murine tumors have shown that the 3 drug combination of PALA + MMPR + 6AN PALA (n-phosphonacetyl aspartate), MMPR (6- methylmercaptopurine riboside), 6AN (6-aminonicotinamide); referred to as PMA is an effective radiation sensitizer. Using the MCF-7 human tumor, we have studied the effects of these drugs on metabolism and cell survival. In vivo studies demonstrate the presence of 6-phosphogluconate (6PG) and a reduction in nucleoside triphosphates after ... |
|
| Regulation of Glucose Transport in Quiescent, Lactating, and Neoplastic Mammary Epithelia |
OCT 1997 |
30 pages |
| Authors:
Peter M. Haney; WASHINGTON UNIV ST LOUIS MO
|
| We studies developmental changes in glucose transporter (GT) targeting in mammary gland, a prerequisite for the understanding GT targeting in breast cancer. Previously, we established that GLUT1 is targeted to Golgi during lactation. To understand the regulation of this process, we carried out subcellular fractionation and density gradient centrifugation, Western blotting, and immunofluorescence in mammary glands of mothers whose pups were prematurely weaned. We conclude: (1) There is enrichment of ... |
|
| Study of the Met Tyrosine Kinase in the Pathogenesis of Breast Cancer |
OCT 1997 |
20 pages |
| Authors:
T. J. Liang; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| Breast cancer is the most common malignancy affecting women in the Western World. Epidemiological studies have defined certain factors that may contribute to the risk of breast cancer, the most important one being a family history of the disease (1, 2). Approximately 5-10% of breast cancers are associated with inherited susceptibility with one or more autosomal dominant traits. Linkage at the estrogen receptor on chromosome 6 has also been reported ... |
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| Function of the Alpha6 in Breast Carcinoma |
OCT 97 |
23 pages |
| Authors:
Arthur M. Mercurio; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| During the first year of this award, we established that the a6% 1 integrin plays an important role in regulating the growth and survival of breast carcinoma. We developed a dominant negative strategy to 'knock-out' the expression of the oc6% 1 integrin in a highly metastatic breast carcinoma cell line (MDA-MB-435). After depletion of a6%l surface expression, these cells are deficient in their growth in the mammary fat pad of ... |
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| A Cohort Study of the Relationship Between c-erbB-2 and Cyclin D1 Overexpression, p53 Mutation and/or Protein Accumulation, and Risk of Progression from Benign Breast Disease to Breast Cancer; and Creation of a Bank of Benign Breast Tissue |
OCT 97 |
39 pages |
| Authors:
Rita A. Kandel; MOUNT SINAI HOSPITAL TORONTO (ONTARIO)
|
| Previously, we determined whether c-erbB-2 overexpression and/or p53 protein accumulation with or without gene mutation are molecular markers of increased breast cancer risk. That investigation, which involved 552 subjects, was conducted as a case-control study nested within a cohort of 5,059 women with benign breast disease (BBD) who participated in the National Breast Screening Study (NBSS). The cohort consists of women with histologically-confirmed diagnoses of BBD for whom paraffin blocks ... |
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| Role of Mammary Prolactin in Carcinogenesis |
OCT 1997 |
11 pages |
| Authors:
Nira Ben-Jonathan; CINCINNATI UNIV OH
|
| A cleaved form of prolactin, named 16K PRL, has been reported to act as an angiostatic agent in several vascular beds. We found that rat mammary gland homogenates can proteolytically cleave PRL and generate 16K PRL. We also detected significant amounts of immunoreactive PRL in human breast tissue and determined that breast cancer cells express PRL receptors and have the capacity to internalize and then release exogenous PRL. Our working ... |
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| Peroxisomal Oxidation in Normal and Tumoral Human Breast |
OCT 1997 |
12 pages |
| Authors:
Gillian Small; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| The peroxisomal enzyme catalase protects aerobic organisms from free radical damage by converting hydrogen peroxide (H2O2) to molecular oxygen and water before it can decompose to form the highly reactive hydroxyl radical. In this manner catalase plays a central role in protecting against cellular oxidative damage. In humans, changes in catalase activity have been implicated in aging and in a number of disease states including cancer. We hypothesized that reduced ... |
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| WNT-Signals and the Regulation of Normal and Cancerous Growth in the Mammary Gland |
OCT 1997 |
19 pages |
| Authors:
Andrew P. McMahon; HARVARD UNIV CAMBRIDGE MA
|
| Wnt genes encode a large family of secreted signaling molecules related to the Drosophila pattern regulating gene wingless. Several members of the Wnt family are implicated in mammary tumorigenesis suggesting that Wnt- activated pathways are a normal component of mammary gland development. Consistent with this hypothesis, we have demonstrated that seven Wnt genes are expressed in the developing mammary gland. One of these, Wnt-7a, appears to be required for epithelial ... |
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| Complementation Screening in Mammalian Cells: Application to Cell Immortalization |
OCT 97 |
23 pages |
| Authors:
Gregory J. Hannon; COLD SPRING HARBOR LAB OF QUANTITATIVE BIOLOGY NY
|
| The defining characteristic of a tumor cell is its ability to proliferate under conditions that prevent the growth of a normal cell. Ultimately, cell proliferation is subject to a genetically programmed limit on the number of divisions that a cell can execute. Studies of human and mouse cells in culture have identified two sequential barriers, M1 (cellular senescence) and M2 (crisis/immortalization), which prevent indefinite division. Circumstantial evidence links the in ... |
|
| Modulation of Molecular Markers by CLA |
OCT 1997 |
52 pages |
| Authors:
Henry J. Thompson; AMC CANCER RESEARCH CENTER DENVER CO
|
| Conjugated linoleic acid (CLA) is a naturally occurring component of the food supply that inhibits mammary carcinogenesis. Data obtained on this project indicate: (1) that the anticancer activity of CLA is unlikely to be explained based soley on its antioxidant activity; (2) that CLA is unlikely to inhibit carcinogenesis by directly antagonizing linoleic acid metabolism; (3) that CLA inhibits carcinogenesis irrespective of the presence or absence of the codon 61 ... |
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| Role of Changes in the Expression of Cyclins and Retinoblastoma Protein in the Development of Breast Cancer |
OCT 1997 |
26 pages |
| Authors:
Thomas A. Langan; COLORADO UNIV AT DENVER
|
| In the first three years of the grant, as described previously and in the present annual report, we have established a panel of 12 available breast cancer and normal breast epithelial cell lines, and characterized them with respect to the expression of a total of 13 cell cycle regulatory proteins by immunoblotting. We also examined 10 matched pairs of normal breast and breast tumor tissue for the expression of Rb ... |
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| Analysis of Multistep Mammary Tumorigenesis in Wnt-1 Transgenic Mice |
SEP 1997 |
20 pages |
| Authors:
Deepa Shankar; CHILDREN'S HOSPITAL LOS ANGELES CA
|
| Mouse mammary tumor virus (MMTV) is used as an insertion mutagen in transgenic mice that express the Wnt1 gene in their mammary gland, to produce additional events like activation of a second oncogene. Cloning cellular sequences flanking new proviral insertion from tumor 76 identified a common insertion locus for MMTV. Further analyses of this region identified Fgf3 as the gene activated over a long distance by ... |
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Reports by Keyword(s)
*MAMMARY GLANDS
