| Urinary Level of Prostaglandin E2 Metabolite and Risk of Incident Breast Cancer |
Jan 2012 |
10 pages |
| Authors:
Sangmi Kim; NATIONAL INST OF ENVIRONMENTAL HEALTH SCIENCES RESEARCH TRIANGLE PARK NC
|
 | This training grant is a Postdoctoral Fellowship Award in breast cancer research, comprising training in breast cancer research and an independent research project. During the previous year, the PI gained valuable experience in designing and conducting molecular epidemiologic studies and participated in various research projects as a leader or a collaborator. She has also acquired knowledge on breast cancer biology through various venues, incorporating new understanding of breast cancer etiology ... |
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| Functional Characterization and Expression of Molluscan Detoxification Enzymes and Transporters Involved in Dietary Allelochemical Resistance |
01-Jun-2008 |
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| Authors:
Kristen E Whalen; MASSACHUSETTS INST OF TECH CAMBRIDGE
|
 | The processes underlying dietary allelochemical tolerance are likely mediated, in part, by biochemical resistance mechanisms that have evolved under the selective pressure of host chemical defenses. Although many have invoked this hypothesis to explain the variation in marine consumer tolerance, few studies have examined the enzymatic diversity and corresponding metabolism of dietary allelochemicals. Molecular and proteomic techniques identified both allelochemically-responsive cytochrome P450s (CYPs), and constitutively expressed glutathione S-transferases (GSTs) and ... |
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| CYP1B1, Oxidative Stress, and Inflammation in the Etiology of Ovarian Epithelial Cancer Using an Avian Model of Ovarian Carcinoma |
01-Nov-2007 |
120 pages |
| Authors:
Dale B Hales; ILLINOIS UNIV AT CHICAGO
|
| Ovarian cancer is the most lethal of the gynecological malignancies due to its late stage of detection. Research in ovarian cancer has been hampered by a lack of suitable animal models. With the exception of the laying hen, no other animal gets ovarian epithelial cancer analogous to the human disease. The study further validates the hen model of ovarian cancer. The results of the study demonstrate that cancer markers in ... |
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| Discovery and Role of a Novel Eicosanoid Family in Breast Cancer |
Aug-2007 |
7 pages |
| Authors:
Claus Schneider; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| There is strong evidence for the induction of the pro-inflammatory enzymes 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) in many types of cancer, including breast cancer. Upregula-tion of both enzymes is associated with promoting tumorigenesis and a negative prognosis of the disease. The 5-LOX (leukotriene) and COX-2 (prostaglandin) pathways have traditionally been viewed as independent biosynthetic routes to eicosanoid lipid hormones, yet recent enzy-mological analyses establish that the 5-LOX product, 5-HETE, is ... |
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| NSAIDS and the Osteogenic Response to Mechanical Stress in Premenopausal Women |
APR 2007 |
19 pages |
| Authors:
Wendy Kohrt; Robert S. Schwartz; COLORADO UNIV HEALTH SCIENCES CENTER DENVER
|
| This is a study of the effects of ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), on the osteogenic response to 9 months of exercise training in healthy, premenopausal women, aged 21 to 40 years (N=102). The hypotheses are: H1a: taking short-acting NSAIDS before exercise will diminish increases in bone mineral density (BMD) in response to exercise training H1b: taking short-acting NSAIDS after exercise will not diminish the increases in BMD in ... |
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| The Effect of COX-2 Inhibitors on the Aromatase Gene (CYP19) Expression in Human Breast Cancer |
DEC 2006 |
28 pages |
| Authors:
Charles L. Shapiro; OHIO STATE UNIV RESEARCH FOUNDATION COLUMBUS
|
| Aromatase (CYP19) is responsible for estrogen biosynthesis, and CYP-19 and cyclooxygenase-2 (COX-2) are both overexpressed in human breast cancers. Prostaglandin activates the CYP19 promotor and increases gene expression therefore we hypothesized that celecoxib, a selective COX-2 inhibitor, will decrease PG and decrease the expression of CYP19. To test this hypothesis, celecoxib was administered to breast cancer patients after the initial core biopsy tumor tissue and then tumor tissue was collected ... |
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| Vitamin D-Prostaglandin Interactions and Effects in Prostate Cancer |
OCT 2006 |
50 pages |
| Authors:
Jacqueline Moreno; LELAND STANFORD JUNIOR UNIV STANFORD CA
|
| 1,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D3 is a hormone with anti-proliferative and prodifferentiation effects in prostate cancer (PCa) cells. Our ultimate goal is to identify novel therapeutic targets for the treatment of PCa with calcitriol. Previous to this study, we have used cDNA microarray analysis of established human PCa cell lines identifying, among others, the regulation of genes implicated in prostaglandin (PG) bioactivity. PGs are implicated in ... |
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| Bone Marrow Function in Development of Childhood Asthma |
OCT 2006 |
22 pages |
| Authors:
Mary B. Hogan; WEST VIRGINIA UNIV RESEARCH CORP MORGANTOWN
|
| Asthma is the most common reason for hospitalization of children in military hospitals. In children with asthma, exposure to allergen results in pulmonary damage due to invasion of eosinophils. Eosinophils are inflammatory cells with limited life spans, and must be continually renewed from the bone marrow. We adapted an animal model of asthma to study the effect of allergen exposure on eosinophil progenitor cells (CFU-eo). These studies have revealed that ... |
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| Neural, Endocrine and Local Mechanisms in the Effects of Environmental Stressors on the Cardiovascular Response to Blood Loss |
AUG 2006 |
8 pages |
| Authors:
James C. Schadt; CURATORS OF THE UNIV OF MISSOURI COLUMBIA
|
| Our studies have provided important, new information about the role of neurohumoral systems as well as the interaction of these systems with local mechanisms in cardiovascular control during blood loss. Although, blood loss surely alters and compromises the highly integrated cardiovascular and respiratory control of oxygen delivery and removal of carbon dioxide, there is little if any published information related to respiratory control during blood loss in conscious animals. We ... |
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| NSAIDS and the Osteogenic Response to Mechanical Stress in Premenopausal Women |
01 OCT 2005 |
7 pages |
| Authors:
Wendy M. Kohrt; Robert S. Schwartz; COLORADO UNIV HEALTH SCIENCES CENTER AURORA CO
|
| This is a study of the effects of ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), on the osteogenic response to 9 months of exercise training in healthy, premenopausal women, aged 21 to 40 years (N=102). The hypotheses are: H1a: taking short-acting NSAIDS before exercise will diminish increases in bone mineral density (BMD) in response to exercise training H1b: taking short-acting NSAIDS after exercise will not diminish the increases in BMD in ... |
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| Vitamin D-Prostaglandin Interactions and Effects on Prostate Cancer |
OCT 2005 |
61 pages |
| Authors:
Jacqueline Moreno; LELAND STANFORD JUNIOR UNIV STANFORD CA
|
| Prostate cancer (PCa) is the most commonly diagnosed malignancy and the second leading cause of cancer death in North American men [1]. According to the American Cancer Society more than 232,000 men will be diagnosed with PCa in 2005 and approximately 10% of these men will die of the disease [1]. Primary therapy for PCa involves the removal of the prostate by surgery or radiation therapy. Unfortunately, after initial treatment ... |
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| Thromboxane Synthase and Prostate Cancer Progression |
JUL 2005 |
11 pages |
| Authors:
Kenneth V. Honn; David Grignon; Daotal Nie; Graham Pidgeon; WAYNE STATE UNIV DETROIT MI
|
| The initiation and progression of prostate cancer remain not well understood to enable development of interventional therapy. Thromboxane synthase is an enzyme downstream of cyclooxygenase, utilizing prostaglandin H to form thromboxane A(sub 2). Using immunohistochemistry analysis, we found that 25% of clinical prostate tumor specimens had strong expression of thromboxane synthase; 33% of cases had medium expression and 42% of cases had weak expression of thromboxane synthase. Prostate cancer cells ... |
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| Bone Marrow Function in Development of Childhood Asthma |
APR 2005 |
18 pages |
| Authors:
Mary B. Hogan; WEST VIRGINIA UNIV MORGANTOWN
|
| Asthma is the most common reason for hospitalization of children in both military and civilian hospitals. In children with asthma, pulmonary exposure to allergen results in damage to bronchioles by invasion of eosinophils. Eosinophils are inflammatory cells, have limited life spans, and must be continually renewed from hematopoietic tissue. We adapted an animal model of asthma to our laboratory for studies of the effect of pulmonary allergen exposure on eosinophil ... |
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| Animal Model of Performance Enhancement by Nutritional Supplements With Anti-Inflammatory Activity |
DEC 2004 |
6 pages |
| Authors:
J. M. Davis; M. D. Carmichael; E. A. Murphy; C. M. Groschwitz; A. Brown; M. R. Zelinski; M. Quig; A. Ghaffar; E. P. Mayer; C. P. Dunne; J. D. Gangemi; SOUTH CAROLINA UNIV COLUMBIA
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| It is well known that intense exercise can induce muscle damage and inflammation depending on exercise mode, intensity, and duration (Schwane et al. , 1983; Willoughby et al., 2003). Exercise with a large eccentric component (lengthening of a muscle that is actively developing tension) produces the greatest muscle fiber damage, inflammation, delayed-onset muscle soreness (DOMS) and various functional deficits. It is now thought that many of these responses to muscle-damaging ... |
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| NSAIDS and the Osteogenic Response to Mechanical Stress in Premenopausal Women |
OCT 2004 |
8 pages |
| Authors:
Wendy M. Kohrt; COLORADO UNIV HEALTH SCIENCES CENTER AURORA CO
|
| The primary aim of this randomized, double-blinded, placebo- controlled trial is to determine the effects of NSAID (ibuprofen) use on the osteogenic response to 9 months of exercise training in 102 women. The scientific rationale for this study centers on the knowledge that the osteogenic response to mechanical stress is a prostaglandin (PG)- dependent process and that NSAIDs inhibit PG synthesis. There is evidence that regular NSAID use inhibits the ... |
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| Heat Shock Protein-70 Inducers and iNOS Inhibitors as Therapeutics to Ameliorate Hemorrhagic Shock |
01 SEP 2004 |
13 pages |
| Authors:
Juliann G. Kiang; Phillip D. Bowman; Baiteng Zhao; James L. Atkins; George C. Tsokos; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
|
| Hemorrhagic shock is the principal cause of death of soldiers in the battlefield. Although the underlying mechanisms are still not fully understood, it has been shown that nitric oxide (NO) overproduction and inducible nitric oxide synthase (iNOS) overexpression play important roles in producing injury caused by hemorrhagic shock. In addition, polymorphonuclear neutrophils (PMN) infiltrate injured tissues and leukotriene B4 (LTB4) generation increases. In a hemorrhage/resuscitation-induced injury model, iNOS, cyclooxygenase-2, and ... |
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| Mechanism of Interaction of Sleep-Affecting Compounds With Neuronal Receptors |
JUL 2004 |
24 pages |
| Authors:
Sergey Bachurin; RUSSIAN ACADEMY OF SCIENCES MOSCOW INST OF PHYSIOLOGICALLY ACTIVE COMPOUNDS
|
| This report results from a contract tasking lnst of Physiologically Active Substances. Russian Academy of Sciences as follows: The goal of this project is to study the mechanism of interaction of some endogenous sleep- affecting compounds with the GABA (gamma aminobutyric acid)- and glutamate receptor channel complexes in neuronal cell culture. Electrophysiological and biochemical methods will be used to assess those interactions. Results will provide new insights into those naturally ... |
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| The Effect of Cox-2 Inhibitors on the Aromatase Gene (CYP19) Expression in Human Breast Cancer |
JUN 2004 |
9 pages |
| Authors:
Charles L. Shapiro; William Burak; Robert Brueggemeier; OHIO STATE UNIV RESEARCH FOUNDATION COLUMBUS
|
| Aromatase (CYP-l9) is responsible for estrogen biosynthesis within breast tumor tissue. Aromatase and cyclooxygenase-2 (COX-2) are both overexpressed in human breast cancer, and increased levels of prostaglandin (PG) activates the CYP19 promotor and increases gene expression. We hypothesize that celecoxib, a selective COX-2 inhibitor, will decrease PG, decrease the expression of CYPl9, and reduce estrogen biosynthesis within tumor tissue. To test this hypothesis, in DOD grant # DAMD17-C-01-0589, tumor tissue ... |
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| Novel COX-2 Inhibitor for Breast Cancer Therapy |
JUL 2003 |
9 pages |
| Authors:
E. P. Reddy; TEMPLE UNIV PHILADELPHIA PA SCHOOL OF MEDICINE
|
| Recent studies have shown that NSAIDS such as aspirin reduce the incidence of human cancers by inhibiting the enzyme Cyclooxygenase (COX), which plays a key role in arachidonic acid metabolism. It is now known that COX exists in at leas two isoforms, term COX-l and COX-2. Of these, COX-2 has also been found to be constitutively expressed in a number of tumor tissues, including breast. The purpose of out study ... |
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| The Effect of COX-2 Inhibitors on the Aromatase Gene Expression in Human Breast Cancer |
JUN 2003 |
4 pages |
| Authors:
Charles L. Shapiro; William Burak; Robert Brueggemeier; OHIO STATE UNIV MEDICAL CENTER COLUMBUS
|
| Aromatase (CYP-19) is responsible for estrogen biosynthesis within breast tumor tissue. Aromatase and cyclooxygenase-2 (COX-2) are both overexpressed in human breast cancer, and increased levels of prostaglandin (PG) activates the CYP19 promotor and increases gene expression. We hypothesize that celecoxib, a selective COX-2 inhibitor, will decrease PG, decrease the expression of CYP19, and reduce estrogen biosynthesis within tumor tissue. To test this hypothesis, in DOD grant # DAMD17-01-1-0589, tumor tissue ... |
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| COX-2 and Prostate Cancer Angiogenesis |
MAR 2003 |
16 pages |
| Authors:
Alice C. Levine; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| Cyclooxygenase-2 (COX-2) is an inducible enzyme which catalyzes the conversion of arachidonic acid to prostaglandins and has previously been demonstrated to play a role in carcinogenesis. We demonstrated that COX-2 and one of its major prostaglandin products, PGE2, are mediators of hypoxia-induced increases in a potent angiogenic factor, VEGF, in a human prostate cancer cell line. In these studies we determined (1) The optimal dosing and timing of administration of ... |
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| NSAIDs and the Osteogenic Response to Mechanical Stress in Premenopausal Women |
OCT 2002 |
6 pages |
| Authors:
Wendy M. Kohrt; Robert S. Schwartz; COLORADO UNIV HEALTH SCIENCES CENTER DENVER
|
| This is a study of the effects of ibuprofen, a non-steroidal anti- inflammatory drug (NSAID), on the osteogenic response to 9 months of exercise training in healthy, premenopausal women, aged 21 to 40 years (N=102) |
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| Enhancing the Effect of Radiation Therapy Using Non-Steroidal Anti- Inflammatory Agents |
SEP 2002 |
75 pages |
| Authors:
C. N. Coleman; S. T. Palayoor; NATIONAL INSTITUTES OF HEALTH BETHESDA MD
|
| Our earlier studies demonstrated that ibuprofen sensitizes prostate cancer cells to radiation in vitro and in vivo. The cytotoxic and radiosensitizing effects of NSAIDs were seen at concentrations that are higher than those that inhibit prostaglandin synthesis. To understand the molecular mechanisms involved in radiosensitization we examined the effects of ibuprofen on several potential cellular targets including COX-2 and transcription factors NFkB and HIFs. NFkB regulates cytokines, growth factors and ... |
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| Molecular Mechanisms of Schwann Cell Proliferation in NF1 |
SEP 2002 |
143 pages |
| Authors:
George H. DeVries; CHICAGO ASSOCIATION FOR RESEARCH AND EDUCATION IN SCIENCE HINES IL
|
| Neurofibromatosis type 1 (NFl) is a genetic disorder characterized by tumors comprised principally of Schwann cells lacking the neurofibromin gene. Our studies concentrated on the metabolic changes that occur in Schwann cells derived from NFl tumors. We documented the following changes: aberrant expression of cell surface receptors, including c-Kit and pDGF, novel pathways stimulated by activation of these receptors leading to the prevention of apoptosis and increased calcium levels, abnormal ... |
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| The Effect of COX-2 Inhibitors on the Aromatase Gene (CYP19) Expression in Human Breast Cancer |
JUN 2002 |
4 pages |
| Authors:
Charles L. Shapiro; William Burak; Robert Brueggemeier; OHIO STATE UNIV RESEARCH FOUNDATION COLUMBUS
|
| Aromatase (CYP-l9) is responsible for estrogen biosynthesis within breast tumor tissue Aromatase and cyclooxygenase-2 (COX-2) are both overexpressed in human breast cancer, and increased levels of prostaglandin (PG) activates the CYPl9 promotor and increases gene expression We hypothesize that celecoxib, a selective COX-2 inhibitor, will decrease PG, decrease the expression of CYPl9, and reduce estrogen biosynthesis within tumor tissue To test this hypothesis, in DOD grant # DAMDl7-0l-0589, tumor tissue ... |
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| A Potential Therapeutic Role of J Series Prostaglandins in PPARy Mediated Treatment of Breast Cancer |
JUN 2002 |
12 pages |
| Authors:
Arta M. Monjazeb; WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF MEDICINE
|
| The peroxisome proliferator activated receptor gamma (PPAR gamma), is a potential therapeutic target for the treatment of breast cancer but the endogenous ligand for PPAR gamma is not yet known. Recent data suggest that the endogenous ligand of PPAR gamma may be a bioactive metabolite of arachidonic acid that is synthesized in normal breast tissue. Activation of PPAR gamma with different agonists (e.g. l5deoxy delta l2,l4PGJ2, troglitazone) elicits different physiological ... |
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| Immune Suppression Following Acute Exposure to Volatile Organic Chemicals |
DEC 2001 |
3 pages |
| Authors:
Stephen E. Ullrich; M D ANDERSON CANCER CENTER HOUSTON TX
|
| The focus of these experiments was to test the hypothesis that dermal application of military jet fuel (JP-8) is immune suppressive. Three specific aims were designed to test this hypothesis: (1) Does dermal exposure to JP-8 induce immune suppression? (2) What are the mechanisms involved? (3) Can you reverse the immune suppressive effects of JP-8? Applying JP-8 to the skins of mice does suppress the immune response. The mechanisms underlying ... |
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| Evaluation of Cyclooxygenase-2 as a Novel Target for Breast Cancer Prevention |
JUL 2001 |
53 pages |
| Authors:
Andrew J. Dannenberg; Louise R. Howe; CORNELL UNIV MEDICAL COLL (WEILL) NEW YORK
|
| The inducible prostaglandin synthase cyclooxygenase-2 (Cox-2) is expressed in a variety of human cancers, but its role in breast cancer has not been definitively established. Our research was designed to test whether Cox-2 is important in the pathogenesis of mammary cancer using Wnt-1 as a model mammary oncogene. Wnt-1 transgenic mice exhibit mammary hyperplasia and subsequently develop mammary carcinomas. Additionally, some mouse mammary epithelial cell lines are transformed by Wnt-1 ... |
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| Pharmacologic Agents for the Management of Asthma in Aircrew |
JUN 2001 |
|
| Authors:
G. W. Gray; DEFENCE AND CIVIL INST OF ENVIRONMENTALMEDICINE DOWNSVIEW (ONTARIO)
|
| Asthma is an inflammatory condition of the airways, producing variable bronchoconstriction. First line therapy is directed at controlling the inflammatory process with agents such as inhaled steroids, nedocromil, and the newer leukotriene inhibitor drugs. In severe cases, systemic steroids or other immunosuppressive therapies may be required for suppression of inflammation. |
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| Effect of Cysteninyl Leukotriene Blockade on the Development of Acute Mountain Sickness |
MAY 2001 |
34 pages |
| Authors:
Stephen R. Muza; David Kaminsky; Charles S. Fulco; Larry A. Sonna; Louis E. Banderet; ARMY RESEARCH INST OF ENVIRONMENTAL MEDICINE NATICK MA
|
| Acute Mountain Sickness (AMS) may be a manifestation of hypoxia- induced cerebral edema resulting, in part, from increased capillary permeability. Leukotrienes (LTB4, LTC4) may be involved in the pathogenesis of AMS, as these compounds are known to increase endothelial permeability. To test the hypothesis that cysteinyl leukotrienes (LTC4) are involved in the development of AMS, we orally administered a cysteinyl leukotriene receptor blocker (montelukast) prior to and during exposure to ... |
|
| Enhancing Effect of Radiation Therapy Using Non-Steroidal Anti- Inflammatory Agents |
APR 2001 |
14 pages |
| Authors:
C. N. Coleman; NATIONAL INSTITUTES OF HEALTH BETHESDA MD
|
| Our earlier studies demonstrated that ibuprofen sensitizes prostate carcinoma cells to radiation in vitro and in vivo. The cytotoxic and radiosensitizing effects of ibuprofen were seen at much higher concentration than that required to inhibit prostaglandin synthesis. To understand the molecular mechanisms involved in radiosensitization we examined the effects of ibuprofen on several potential cellular targets including COX-2 and transcription factor NFkB. COX-2 was constitutively expressed in PC3 cells and ... |
|
| Cox-2 and Prostate Cancer Angiogenesis |
MAR 2001 |
28 pages |
| Authors:
Alice C. Levine; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| Cyclooxygenase-2 (COX-2) is an inducible enzyme which catalyzes the conversion of arachidonic acid to prostaglandins and has previously been demonstrated to play a role in carcinogenesis. We demonstrated that COX-2 and one of its major prostaglandin products, PGE2, are mediators of hypoxia-induced increases in a potent angiogenic factor, VEGE, in a human prostate cancer cell line. In these studies we are determining (1) the optimal dosing and timing of a ... |
|
| Percutaneous Absorption of Chemical Mixture Relevant to the Gulf War |
FEB 2001 |
|
| Authors:
Jim E. Riviere; Nancy A. Monteiro-Riviere; Ronald E. Baynes; NORTH CAROLINA STATE UNIV AT RALEIGH
|
| The purpose of this research is to quantitate the dermal absorption and cutaneous toxicity of chemical mixtures relevant to the Gulf War. The primary focus of year 2 of this proposal was to assess 1) the effect that systemic exposure to pyridostigmine bromide (PB) has on DEBT and permethrin absorption; 2.) the effect of topical and systemic exposure of DFP (CW nerve agent simulant) on absorption of these chemicals, and ... |
|
| Dietary Prevention of Breast Cancer |
SEP 2000 |
40 pages |
| Authors:
Leena A. Hilakivi-Clarke; GEORGETOWN UNIV WASHINGTON DC MEDICAL CENTER
|
| The purpose of the project is to appraise critically the state of dietary prevention of breast cancer and to forge new avenues of investigation in the field of nutrition. A special emphasis is on the role of diet during fetal life, puberty, and pregnancy, in influencing breast development and breast cancer risk (task-1) . In addition, the data we obtain using animal models serve as a basis of developing and ... |
|
| Molecular Mechanisms of Schwann Cell Proliferation in NF1 |
SEP 2000 |
66 pages |
| Authors:
George H. DeVries; CHICAGO ASSOCIATION FOR RESEARCH AND EDUCATION IN SCIENCE HINES IL
|
| Further studies documenting the molecular mechanisms responsible for Schwann cell proliferation in NFl- derived Schwann cell lines have been carried out. We have documented that the absence of neurofibromin leads to the presence of the tyrosine kinase receptors cKit and PDGF receptor in these Schwann cell lines. C-Kit is expressed early in normal Schwann cell development, where it does not play a role in proliferation, differentiation, or acting as a ... |
|
| The Role of Breast Cancer Derived Prostaglandin E2 in the Elaboration of a Therapeutic Immune Response |
JUL 2000 |
23 pages |
| Authors:
Stephen Eck; PENNSYLVANIA UNIV PHILADELPHIA
|
| The principal goal was to understand why breast cancer cells are able to evade the host immune system despite the presence of tumor antigens and tumor antigen-specific T lymphocytes. We had previously demonstrated that tumor- derived prostaglandin E2 (PGE2) directly contributes to the lack of a significant immune response to breast cancer cells. However, the production of PGE2 by breast cancer cells did not completely explain the immune suppressive effect ... |
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| Evaluation of Cycloogenase-2 as a Novel Target for Breast Cancer Prevention |
JUL 2000 |
18 pages |
| Authors:
Andrew J. Dannenberg; CORNELL UNIV MEDICAL COLL NEW YORK
|
| Cyclooxygenase (Cox) catalyzes the synthesis of prostaglandins and the intracellular production of mutagens from procarcinogens. Cox-2, the inducible form of cyclooxygenase, is expressed in a wide variety of human cancers, but its role in breast cancer has not been established. Our research is designed to test whether Cox-2 contributes to mammary cancer, using Wnt-1-1 as a model mammary oncogene. The role of Cox-2 in mammary tumorigenesis is being tested by ... |
|
| Enhancing Effect of Radiation Therapy Using Non-Steroidal Anti- Inflammatory Agents |
OCT 1999 |
15 pages |
| Authors:
C. N. Coleman; DANA-FARBER CANCER INST BOSTON MA
|
| Following studies with ibuprofen that demonstrated radiation sensitization with prostate cancer cells in vivo and in vitro, we are examining the potential targets of cellular radio sensitization. We observed that NSAIDs inhibited the prostaglandin synthesis at much lower concentrations than those required to induce cytotoxicity and radio sensitization, suggesting that the cellular sensitization appears to be a target other than cyclooxygenases. The mechanisms currently ... |
|
| Evaluation of Cycloogenase-2 as a Novel Target for Breast Cancer Prevention |
JUL 1999 |
13 pages |
| Authors:
Andrew J. Dannenberg; CORNELL UNIV MEDICAL CENTER NEW YORK
|
| Cyclooxygenase (Cox) catalyzes both prostaglandin synthesis and the production of mutagens. Cox-2, the inducible form of COX, is expressed in a variety of human cancers but its role in breast cancer has not been established. Our research is designed to test whether Cox-2 is important in the pathogenesis of mammary cancer, using Wnt-l as a model mammary oncogene. Wnt-l transgenic mice exhibit mammary hyperplasia and subsequently develop mammary carcinomas. The ... |
|
| The Role of Prostaglandin G/H Synthase 2 in the Apoptosis of Human Mammary Epithelial Cells |
JUN 1999 |
33 pages |
| Authors:
Robert W. Fisher; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| We are examining apoptotic pathways that may be altered in human mammary epithelial cells as a consequence of the overexpression of prostaglandin G/H synthase 2. We have shown that human mammary epithelial cells express high levels of prostaglandin G/H synthase, are resistant to ionizing radiation- induced apoptosis, but do apoptose when exposed to the broad spectrum kinase inhibitor staurosporine or to DNA damage caused by hydrogen ... |
|
| Breast Cancer and Estrogen Biosynthesis in Adipose Tissue |
OCT 1998 |
185 pages |
| Authors:
Serdar E. Bulin; TEXAS UNIV AT DALLAS
|
| The long-term objective of this application was to determine the cellular and molecular mechanisms responsible for increased aromatase expression in breast adipose fibroblasts proximal to malignant epithelial cells. Our results are supportive of the following hypothesis: Regional differences in relative proportions of histological components of the breast adipose tissue (e. g., fibroblasts vs. mature adipocytes) may be the primary cause of estrogenic concentration gradients, since regions ... |
|
| Mechanisms of PCBS-Induced Breast Cancer |
SEP 1997 |
22 pages |
| Authors:
Larry W. Robertson; KENTUCKY UNIV LEXINGTON
|
| Our research is aimed at the Investigation of the effects of polychiorinated biphenyls (PCBs) in breast cancer. PCBs are industrial chemicals which persist in our environment. The lipophilicity of PCBs and their tendency to bioaccumulate in adipose tissue and breast milk raise concern about the health risks associated with exposure to PCBs and related compounds. Commercial PCB mixtures are complete carcinogens, producing hepatocellular carcinomas in rats and mice, but the ... |
|
| Dietary Carcinogens and Breast Cancer |
JUL 1997 |
27 pages |
| Authors:
James W. Gaubatz; UNIVERSITY OF SOUTH ALABAMA MOBILE
|
| We have investigated phase II activation of the food-derived mutagen 2-hydroxyamino-1-methyl-6-phenyl4,5-Bpyridine (N-OH-PhIP) by cytosolic acetyltransferase, sulfotransferase, and tRNA synthetase/kinase enzymes from human breast tissue. Cytosol from homogenates of mammary gland tissue obtained from breast reduction surgery or mastectomy was incubated with and without enzyme-specific cofactors, and mutagen binding to calf thymus DNA was quantified by 32P-postlabeling. In addition, microsomal fractions of mammary epithelial cells from some individuals were examined for ... |
|
| The Role of Prostaglandins in the Growth of Breast Epithelial Cells |
06 SEP 95 |
30 pages |
| Authors:
Stephen M. Prescott; UTAH UNIV SALT LAKE CITY
|
| The growth of mammary epithelial cells in response to growth factors is augmented by linoleic or arachidonic acid. This may explain the association between dietary fatty acid intake and increased risk of breast cancer. We are exploring the mechanism by which these fatty acids exert this growth-promoting effect with the central hypothesis that oxidative metabolism is a crucial step. Moreover, we are testing the hypothesis that induction of prostaglandin H ... |
|
| Mechanism of Cutaneous Vesication |
17 FEB 94 |
117 pages |
| Authors:
Nancy A. Monteiro-Riviere; Jason Z. Zhang; Alfred O. Inman; Jim D. Brooks; Jim E. Riviere; NORTH CAROLINA STATE UNIV AT RALEIGH SCHOOL OF VETERINARY MEDICINE
|
| This project investigated the mechanism of bis (2-chloroethyl) sulfide (sulfur mustard, HD)-induced cutaneous vesication using the isolated perfused porcine skin flap (IPPSF) and in vitro cell cultures. Treatment of IPPSFs with 5.0 mg/ml of HD results in a characteristic increase in vascular resistance, decrease in glucose utilization, and the formation of gross and microblisters. The first study demonstrated that the vascular changes associated with HD vesication are accompanied by increases ... |
|
| Involvement of Lipid Metabolism in Chemical Transmission Processes at Mossy Fiber Synapses |
24 MAY 93 |
8 pages |
| Authors:
Robert V. Dorman; KENT STATE UNIV OH DEPT OF BIOLOGICAL SCIENCES
|
| Isolated hippocampal mossy fiber synaptosomes were used to assess the relationships between membrane lipid metabolism and the evoked release of the excitatory amino acid neurotransmitter glutamate. A variety of metabolic parameters were investigated in order to develop a comprehensive model for the mechanisms of transmitter release. Mossy fiber terminals were radiolabeled with 3H arachidonic acid and the effects of membrane depolarization and calcium influx on the labeling of the component ... |
|
| Studies on the Pathogenesis of BIS (2-Chloroethyl) Sulfide (HD) Induced Vesication in Porcine Skin |
13 MAY 1993 |
11 pages |
| Authors:
N. A. Monteiro-Riviere; A. O. Inman; J. W. Spoo; R. A. Rogers; J. E. Riviere; NORTH CAROLINA STATE UNIV AT RALEIGH
|
| HD is a potent vesicant whose pathogenesis remains speculative. Previous work with the isolated perfused porcine skin flap (IPPSF) described the HD dose-response relationship. The present work includes a time-response study, probes the effects of alterations in basal perfusion parameters (glucose concentration, perfusate flow), and assesses the prostaglandin (PGE2, 6-keto PGF1a) profile of HD vesication. immunohistochemistry and immunoelectron microscopy created a map of the epidermal-dermal junction epitopes in HD-induced blisters. ... |
|
| Effects of Perfluoroisobutene on Guinea Pig Isolated Lung Preparations. |
13 MAY 1993 |
|
| Authors:
Andrew P. Bowditch; Helen Jones; CHEMICAL AND BIOLOGICAL DEFENCE ESTABLISHMENT PORTON DOWN (UNITED KINGDOM)
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| Effects of perfluoroisobuteno (PFIB) on lung pharmacology were investigated using three preparations: The isolated, ventilated, perfused lung (IVPL), the tracheally-perfused lung (TPL) and the tracheal strip (TS). The IVPL taken from PFIB exposed animals showed decreased tidal volume (TV) and compliance (Cdyn), and increased lung resistance (LR), but no PFIB-induced chemical mediator release was detected by bioassay. in vitro inhalation exposure of the IVPL to PFIB caused a dose-related, reversible ... |
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| Magnetic Resonance Elucidation of Molecule/Macromolecule Interaction Stereochemistry |
09 JUL 92 |
8 pages |
| Authors:
Niels H. Andersen; UNIV OF WASHINGTON SEATTLE DEPT OF CHEMISTRY
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| our primary accomplishments were the development of software for the computer-aided structure elucidation of structural features of biological systems based on NOESY data: (a) simulating accurate theoretical NOESY spectra based on structural models, motional assumptions and NMR experiment parameters; and (b) the automated extraction of modeling constraints directly from raw NOESY data. The most recent software developments are the incorporation of model-free order parameters into NOESY simulations and the addition ... |
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| Magnetic Resonance Elucidation of Molecule/Macromolecule Interaction Stereochemistry |
08 JUL 92 |
5 pages |
| Authors:
Niels H. Andersen; UNIV OF WASHINGTON SEATTLE DEPT OF CHEMISTRY
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| The work originally proposed for contract N00014-88-K-0202 has been continued and brought to a conclusive point where the methods can be used by other workers. The most recent software developments are the incorporation of model-free order parameters into NOESY simulations and the addition of routines for comparing computer-extracted distances (or cross-rates) with the expectation ranges based on the full spectrum of torsional freedom so as to generate precision estimates for ... |
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