| Health Status and Performance of United States Air Force Airmen Following Mild Traumatic Brain Injury |
Sep-2009 |
8 pages |
| Authors:
Timothy S Wells; AIR FORCE RESEARCH LAB WRIGHT-PATTERSON AFB OH
|
 | The objectives of this study are as follows: (1) determine the agreement between the Centers for Disease Control (CDC) definition of mild traumatic brain injury (mTBI) and the clinical judgment of a board-certified neurologist based upon medical records review; (2) utilize a historical prospective study design in a large, well-documented population to determine the relation between mTBI and mental disorders. including depression, PTSD, anxiety disorders, sleep disorders, fatigue, headache, and ... |
|
| Endocrine Therapy of Breast Cancer |
Jun-2009 |
|
| Authors:
Robert Clarke; GEORGETOWN UNIV WASHINGTON DC
|
 | A controversy in the treatment of estrogen receptor positive (ER+) breast cancers is whether an aromatase inhibitor, e.g., letrozole (LET) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., 40% of tumors show cross resistance to TAM or an aromatase inhibitor on crossover. Only 50% of ... |
|
| Alcohol Intoxication Impact on Outcome from Traumatic Injury |
01-May-2009 |
11 pages |
| Authors:
Patricia Molina; LOUISIANA STATE UNIV NEW ORLEANS
|
| Acute alcohol intoxication (AAI) impairs the hemodynamic counteregulatory response to trauma and hemorrhagic shock (HS), blunts the pressor response to fluid resuscitation (FR), suppresses the HS-induced neuroendocrine response, impairs pro-inflammatory cytokine expression and increases mortality from infection during recovery. Studies conducted during this funding period examined (a) whether the attenuated neuroendocrine response, particularly reduced sympathetic nervous system (SNS) activation, is the principal mechanism responsible for the hemodynamic instability seen in ... |
|
| Alcohol Intoxication Impact on Outcome from Traumatic Injury |
01-May-2008 |
9 pages |
| Authors:
Patricia Molina; LOUISIANA STATE UNIV HEALTH SCIENCES CENTER NEW ORLEANS DEPT OF PHARMACOLOGY
|
| Acute alcohol intoxication (AAI) impairs the hemodynamic counteregulatory response to trauma and hemorrhagic shock (HS), blunts the pressor response to fluid resuscitation (FR), suppresses the HS-induced neuroendocrine response, impairs pro-inflammatory cytokine expression and increases mortality from infection during recovery Studies conducted during this funding period examined a) whether the attenuated neuroendocrine response, particularly reduced sympathetic nervous system (SNS) activation, is the principal mechanism responsible for the hemodynamic instability seen in ... |
|
| Biomarkers of Risk for Post-Traumatic Stress Disorder (PTSD) |
01-May-2008 |
21 pages |
| Authors:
Audrey R Tyrka; BUTLER HOSPITAL PROVIDENCE RI
|
| The objective of this proposal is to study genetic and neuroendocrine biomarkers of risk in a carefully assessed population of military personnel who have recently returned from war zones. The target sample includes 300 men and women who have recently returned from hazardous deployment and are undergoing a comprehensive assessment of symptoms and stressors in a related 12-month longitudinal study. To date, we have enrolled 125 subjects. Samples of saliva ... |
|
| Function of PTP1B in Neuroendocrine Differentiation of Prostate Cancer |
JAN 2008 |
33 pages |
| Authors:
Jiaoti Huang; ROCHESTER UNIV NY
|
| The goal of the project is to identify the molecular mechanisms responsible for therapeutic failure in prostate cancer patients receiving hormonal therapy Scope: The scope of the project is to use prostate cancer cell lines in in-vitro cell culture systems to study the complex signal transduction pathways that may be responsible for the neuroendocrine differentiation of prostate cancer cells, particularly the relationship of PTP1B to IL-8 signaling through its receptors ... |
|
| Stressful Military Training: Endocrine Reactivity, Performance, and Psychological Impact |
Dec-2007 |
9 pages |
| Authors:
Jared P Reis; Marcus K Taylor; Kenneth P Sausen; Lilianne R Mujica-Parodi; Eric G Potterat; Amanda E Markham; Genieleah A Padilla; Deborah L Taylor; NAVAL HEALTH RESEARCH CENTER SAN DIEGO CA
|
| We examined the responsiveness of both cortisol and dehydroepiandrosterone sulfate (DHEAS) to the stress of survival training in military men and evaluated relationships to performance, peritraumatic dissociation, and the subsequent impact of stressful events. |
|
| ERR Gamma: Does an Orphan Nuclear Receptor Link Steroid Hormone Biogenesis to Endocrine Resistance? |
01 SEP 2007 |
39 pages |
| Authors:
Rebecca B. Riggins; GEORGETOWN UNIV WASHINGTON DC
|
| Estrogen-related receptor gamma (ERR gamma) is an orphan nuclear receptor with structural similarities to ER alpha and ER beta (1). In addition to its ability to transactivate classical and imperfect estrogen response elements (EREs) ERR gamma is a potent activator of transcription from steroidogenic factor-1 (SF-1) response elements (SF-1REs). Many genes regulated by SF-1REs control key aspects of cholesterol and fatty acid synthesis important not only for generation of the ... |
|
| Neural Control of Hemorrhage-Induced Tissue Cytokine Production |
31 MAR 2007 |
5 pages |
| Authors:
Patrica E. Molina; LOUISIANA STATE UNIV HEALTH SCIENCES CENTER NEW ORLEANS DEPT OF PHARMACOLOGY
|
| Studies performed under this grant provided evidence that tissue injury and hypoperfusion activate systemic and central neural, hormonal and opiate mechanisms that regulate the hemodynamic, metabolic and proinflammatory counter regulatory responses involved in restoring homeostasis following trauma/hemorrhage. Opiate pathway activation favors hemodynamic instability and a pro-inflammatory tissue response while sympathetic nervous system activation counteracts the inflammatory response and contributes to cardiovascular responsiveness. Our studies demonstrated that the intact neuroendocrine response ... |
|
| A Novel Amphibian Tier 2 Testing Protocol: A 30-Week Exposure of Xenopus Tropicalis to the Antiandrogen Flutamide |
2007 |
11 pages |
| Authors:
Paul L. Knechtges; Robert L. Sprando; Karen L. Porter; Linda M. Brennan; Mark F. Miller; David M. Kumsher; William E. Dennis; Charles C. Brown; Eric D. Clegg Paul L. Knechtges. Robert L. Sprando. Karen L. Potter.; ARMY CENTER FOR ENVIRONMENTAL HEALTH RESEARCH FORT DETRICK MD
|
| In 1996, the U.S. Congress mandated the development of a screening program for endocrine-disrupting chemicals (EDCs) using validated test systems. Subsequently, the Endocrine Disruptor Screening and Testing Advisory Committee recommended the development of a standardized amphibian assay for tier 2 testing of EDCs. For that reason, a tier 2 testing protocol using Xenopus (Silurana) tropicalis and a 30-week, flow-through exposure to the antiandrogen flutamide from stage 46 tadpoles through sexually ... |
|
| Castration Induced Neuroendocrine Mediated Progression of Prostate Cancer |
SEP 2006 |
8 pages |
| Authors:
Christopher P. Evans; CALIFORNIA STATE UNIV SACRAMENTO
|
| In the past twelve months we have demonstrated that bombesin stimulates the androgen receptor preferentially to a proximal androgen response element in the promoter region rather than in the enhancer region, which is primarily stimulated by androgens. We have shown that gastrin-releasing peptide prostate cancer cells have their growth in soft agar inhibited by the specific Src inhibitor AZD0530. This is a dose-dependent response. AZD0530 abolishes the nuclear translocation of ... |
|
| Studies of a RAS Antagonist in Breast Cancer |
MAY 2006 |
24 pages |
| Authors:
Richard J. Santen; VIRGINIA UNIV CHARLOTTESVILLE
|
| Deprivation of estrogen, called Endocrine Therapy (ET), is commonly used to treat women with estrogen receptor (ER) positive breast cancer. Resistance to ET occurs in many women after about 18 months of treatment. Upregulation of growth factor pathways mediated by the 21 kD RasGTPase protein may contribute to resistance to ET. A novel Ras antagonist, farnesylthiosalicylate (FTS) causes Ras downreguation with concomitant abrogation of growth factor pathways. We tested the ... |
|
| Molecular Markers of Estrogen Metabolism and Progression From High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) to Prostate Cancer |
FEB 2006 |
22 pages |
| Authors:
Jay H. Fowke; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| The purpose of this case-control study is to investigate the association between genetic and encocrine markers of estrogen metabolism and prostate cancer progression. Androgens (e.g., testosterone) may be critical in prostate cancercinogenesis, but there is accumulating evidence that estrogens facilitate progress during the later stages of prostate cancer formation 1-4. To explore the role of estrogens in human prostate carcinogenesis, we proposed to investigate the association between genetic and endocrine ... |
|
| Inhibitory Ah Receptor-Androgen Receptor Crosstalk in Prostate Cancer |
FEB 2006 |
93 pages |
| Authors:
Stephen Safe; TEXAS A AND M UNIV COLLEGE STATION
|
| Treatment for prostate cancer depends on multiple factors including the stage of the tumor and expression of the androgen receptor (AR). Endocrine therapy can be used for treatment of early stage androgen-responsive tumors, whereas chemotherapy for later stage androgennon responsive tumors is problematic. We investigated the aryl hydrocarbon receptor (AhR) as a potential target for treating prostate cancer using a new series of relatively non-toxic selective AhR modulators (SAhRMs). Initial ... |
|
| Assessment of Protocol Designed to Detect Endocine Disrupting Effects of Flutamide in Xenopus Tropicalis |
JAN 2006 |
45 pages |
| Authors:
Paul L. Kenchtges; Robert L. Sprando; Linda M. Bremman; Mark F. Miller; David M. Kumsher; William E. Dennis; Charles C. Brown; Eric D. Clegg; ARMY CENTER FOR ENVIRONMENTAL HEALTH RESEARCH FORT DETRICK MD
|
| This technical report represents a pilot study to test a new protocol with an amphibian frog species, Xenopus tropicalis, for possible application in the U.S. Environmental Protection Agency (USEPA) Endocrine Disruptor Screening and Testing Program. The frogs were exposed to the model anti-androgenic compound flutamine under flow-through conditions for a period of 30 weeks, beginning at 48 hours post-hatch. The endpoints evaluated for this study were (1) overall health of ... |
|
| Mechanism of Ovarian Epithelial Tumor Predisposition in Individuals Carrying Germline BRCA1 Mutations |
JAN 2006 |
25 pages |
| Authors:
Louis Dubeau; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| Women with germline mutations in BRCA1 are strongly predisposed to cancers of the ovary and fallopian tubes. Given the strong link between menstrual activity and risk of ovarian cancer in the general population, we hypothesized that BRCA1 might predispose to ovarian cancer indirectly, by influencing ovarian granulosa cells, which play an important role in controlling menstrual cycle progression. We used the Cre-lox system to inactivate the mouse Brca1 gene in ... |
|
| Human Endocrine Responses to Exercise-Cold Stress |
28 SEP 2005 |
14 pages |
| Authors:
J. W. Castellani; D. W. Degroot; ARMY RESEARCH INST OF ENVIRONMENTAL MEDICINE NATICK MA THERMAL AND MOUNTAIN MEDICINE DIVISION
|
| The combination of cold exposure and exercise performed in this environment elicits profound physiological responses. These include increases in metabolic heat production and vasoconstriction in order to maintain body temperature, changes in fluid balance and changes in substrate mobilization in order to fuel increased metabolic activity. Many of these physiological responses are associated with endocrine secretion and concentration changes. It is acknowledged that differences in plasma levels as a result ... |
|
| Definition of the Molecular Mechanisms Which Distinguish Between Selective Estrogen Receptor Modulators (SERMs) and Full Antiestrogens |
14 SEP 2005 |
15 pages |
| Authors:
Huey-Jing Huang; DUKE UNIV MEDICAL CENTER DURHAM NC
|
| Tamoxifen, a SERM (Selective Estrogen Receptor Modulator), is the most commonly used endocrine treatment for all stages of breast cancer. However, progression from tamoxifen sensitivity to tamoxifen resistance occurs in a substantial portion of the tumors. Full antiestrogens, such as ICI 182,7&0, are currently used as the second line therapy after-failure of long-term tamoxifen therapy. To facilitate the design and characterization of more appropriate therapeutic agents for endocrine therapy of ... |
|
| Gene-Environment Interaction and Breast Cancer on Long Island, NY |
14 SEP 2005 |
7 pages |
| Authors:
Susan L. Teitelbam; MOUNT SINAI MEDICAL CENTER OF THE CITY OF NEW YORK
|
| This research project will build upon the Long Island Breast Cancer Study Project (LIBCSP), a large population based, case-control study of the environment and breast cancer. Participants completed an in-person interviewer-administered interview, donated blood and urine samples and had home environment samples (dust, soil and water) collected. For this study, 200 cases and 200 controls who donated urine samples will be selected and their urine samples will be analyzed for ... |
|
| CtlP (RBBP8) a Critical Player in the Development of Tamoxifen Resistance in Human Breast Cancer |
SEP 2005 |
12 pages |
| Authors:
C. M. Aldaz; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Tamoxifen resistance constitutes a major clinical challenge in breast cancer therapy. However, the mechanisms involved are still poorly understood. Using serial analysis of gene expression (SAGE) based profiling of our recently developed tamoxifen resistant human breast cancer cell line, we identified CtIP, a BRCA1- and CtBP-interacting protein, as one of the most significantly down-regulated transcripts in tamoxifen resistant cells. This result was independently confirmed by quantitative real-time RT-PCR and Western ... |
|
| Functional Analysis of Drosophila NF1 |
JUL 2005 |
15 pages |
| Authors:
Andre Bernards; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| The protein that is defective in patients with neurofibromatosis type 1 (NF1) functions as a GTPase Activating Protein (GAP) for Ras, yet homozygous loss of a highly conserved Drosophila NF1 ortholog results in several phenotypes that are insensitive to manipulating Ras signal transduction, but rescued by increasing signaling through the cyclic AMP-dependent protein kinase A (cAMP/PkA) pathway. To study how NF1 modulates this pathway and to evaluate whether the cAMP/PKA ... |
|
| Endocrine Therapy of Breast Cancer |
JUN 2005 |
39 pages |
| Authors:
Robert S. Clarke; GEORGETOWN UNIV WASHINGTON DC
|
| A recent controversy in the treatment of estrogen receptor positive (ER+) breast cancers is whether an aromatase inhibitor, e.g., letrozole (LET) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., -40% of tumors show crossresistance to TAM or an aromatase inhibitor on crossover. Only 50% of ... |
|
| Autocrine and Paracrine Control of Breast Cancer Growth by Sex Hormone-Binding Globulin |
APR 2005 |
21 pages |
| Authors:
William Rosner; Scott M. Kahn; SAINT LUKE'S-ROOSEVELT INST FOR HEALTH SCIENCES NEW YORK NY OFFICE OF GRANTSAND RESEARCH ADMINISTRATION
|
| The plasma protein sex hormone-binding globulin (SHBG) not only binds estrogens in plasma, but also is part of an estrogen signal transduction system that starts with a receptor (R-shbg) for SHBG on breast cell membranes. The SHBG-R-shbg complex is activated by an appropriate steroid hormone, e.g., estradiol (E2), (forming the new complex, E2-SHBG-R-shbg), to trigger a second messenger system to produce cAMP minutes after steroid binding. Frozen sections of normal ... |
|
| Acquired Tamoxifen Resistance and Overexpression of Anti-Apoptotic Molecules: A Potential Strategy for Overcoming Endocrine Resistance |
FEB 2005 |
13 pages |
| Authors:
Marc Lippman; Liang Xu; MICHIGAN UNIV ANN ARBOR
|
| The major goal of this Concept Award project is to investigate whether a small molecule inhibitor of Bcl-xL will be able to overcome the chemo- and endocrine-resistance in breast cancer. we have investigated the in vitro and anti-tumor activity of (-)-gossypol, a potent small molecule inhibitor of Bcl- XL, and the potential synergistic effects of (-)-gossypol in combination with chemodrugs and Tamoxifen in breast cancer cell lines. (-)-gossypol showed potent ... |
|
| Role of Tumor Microenvironment and the FGF Signaling Axis on Differentiation and Emergence of the Neuroendocrine Phenotype in Prostate Cancer |
FEB 2005 |
23 pages |
| Authors:
Andreas I. Evangelou; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Specific changes in the fibroblast growth factor (FGF) signaling axis can abrogate stromal-epithelial interactions to modify the microenvironment of the prostate gland. We have previously demonstrated that signaling through ECK receptor 1 (FGFR1) but not FGFR2 promoted emergence of epithelial to neuroendocrine transition (ENT) . We have established protocols to introduce constitutively active receptors in prostate epithelial cells and measure expression of genes associated with epithelial (E-cadherin), stromal (Cadherin- 11), ... |
|
| Inhibitory Ah Receptor-Androgen Receptor Crosstalk in Prostate Cancer |
FEB 2005 |
25 pages |
| Authors:
Stephan H. Safe; TEXAS A AND M RESEARCH FOUNDATION COLLEGE STATION
|
| Treatment for prostate cancer depends on multiple factors including the stage of the tumor and expression of the androgen receptor (AR) . Endocrine therapy can be used for treatment of early stage androgen-responsive tumors, whereas chemotherapy for later stage androgen- nonresponsive tumors is problematic. We have investigated the aryl hydrocarbon receptor (AhR) as a potential target for treating prostate cancer using a new series of relatively non-toxic selective AhR modulators ... |
|
| Molecular Markers of Estrogen Metabolism and Progression from High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) to Prostate Cancer |
FEB 2005 |
14 pages |
| Authors:
|
| The purpose of this case-control study is to investigate the association between genetic and endocrine markers of estrogen metabolism and prostate cancer progression. Androgens (e.g., testosterone) may be critical in prostate carcinogenesis, but there is accumulating evidence that estrogens facilitate progress during the later stages of prostate cancer formation. To explore the role of estrogens in human prostate carcinogenesis, we proposed to investigate the association between genetic and endocrine markers ... |
|
| Mechanism of Ovarian Epithelial Tumor Predispostion in Individuals Carrying Germline BRCA1 Mutations |
JAN 2005 |
32 pages |
| Authors:
Louis Dubeau; CALIFORNIA UNIV LOS ANGELES
|
| Women with germline mutations in BRCA1 are strongly predisposed to cancers of the ovary and fallopian tubes. Given the strong link between menstrual activity and risk of ovarian cancer in the general population, we hypothesized that BRCA1 might predispose to ovarian cancer indirectly, by influencing ovarian granulosa cells, which play an important role in controlling menstrual cycle progression. We used the Cre-lox system to inactivate the mouse Brca1 gene in ... |
|
| Identification of Signaling Proteins the Modulate Androgen Receptor Activity |
NOV 2004 |
8 pages |
| Authors:
Zhou Songyang; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Androgens and the androgen receptor (AR) play a critical role in the development and progression of prostate cancers. The majority of prostate cancers initially respond to endocrine treatment (androgen dependent), but eventually become androgen independent that prove fatal. It appears that a functionally active AR may contribute to the progression of androgen-independent prostate cancers. Understanding the signaling pathways that regulate androgen- dependent and - independent activation of AR mediated transcription ... |
|
| Structural Determination of Certain Novel ER Complexes |
SEP 2004 |
16 pages |
| Authors:
Ya-Ling Wu; Geoffrey L. Greene; CHICAGO UNIV IL
|
| Tamoxifen is effective for the prevention and treatment of estrogen- dependent breast cancers, but is associated with an increased incidence of endometrial tumors. We completed the first aim of this proposal to solve the crystal structure of the estrogen receptor alpha ligand-binding domain (ER alpha LBD) bound to the structurally similar compound GW5638, which has therapeutic potential and does not stimulate the uterus. Like tamoxifen, GW5638 relocates the carboxy-terminal helix ... |
|
| Fatigue Countermeasures for Rapid Deployment: Operation Pegasus |
JUL 2004 |
35 pages |
| Authors:
Jon French; Jeff Whitmore; Didier Lagarde; Maurice Beaumont; Terrell Scoggins; AIR FORCE RESEARCH LAB BROOKS AFB TX HUMAN EFFECTIVENESS DIR/ BIODYNAMICS ANDPROTECTION DIV
|
| The aim of this work was to investigate the effects of slow-release caffeine (SRC) and melatonin (MLT) on sleep and daytime vigilance and SRC or MLT as chronobiotics after a 7-time zone eastbound flight. Three groups of 9 US Air Force reservists each received either five daily doses of SRC (300 mg), four nightly doses of MLT (5 mg) or the appropriate placebo for SRC or MLT in a double-blind, ... |
|
| Definition of the Molecular Mechanisms Which Distinguish Between Selective Estrogen Receptor Modulators (SERMs) and Full Antiestrogens |
MAY 2004 |
15 pages |
| Authors:
Huey-Jing Huang; DUKE UNIV MEDICAL CENTER DURHAM NC
|
| The antiestrogen tamoxifen is the most commonly used endocrine treatment for all stages of breast cancer. Tamoxifen is a SERM (Selective Estrogen Receptor Modulator) which can act as an estrogen or an antiestrogen depending on the tissues in which it operates. Initially, tamoxifen may have profound effects on the survival and proliferation of breast cancer cells, but progressively, resistance emerges through mechanisms that are only partially understood. Some pure antiestrogens ... |
|
| Molecular Markers of Estrogen Metabolism and Progression From High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) to Prostate Cancer |
MAR 2004 |
11 pages |
| Authors:
Jay H. Fowke; VANDERBILT UNIV MEDICAL CENTER ATLANTA GA
|
| The purpose of this case-control study is to investigate the association between genetic and encocrine markers of estrogen metabolism and prostate cancer progression. Androgens (e.g., testerone) may be critical in prostate cancercinogenesis, but there is accumulating evidence that estrogens facilitate progress during the later stages of prostate cancer formation (1-4). To explore the role of estrogens in human prostate carcinogenesis, we proposed to investigate the association between genetic and endocrine ... |
|
| Inhibitory Ah Receptor - Androgen Receptor Crosstalk in Prostate Cancer |
FEB 2004 |
29 pages |
| Authors:
Stephen H. Safe; TEXAS A AND M RESEARCH FOUNDATION COLLEGE STATION
|
| Treatment for prostate cancer depends on multiple factors including the stage of the tumor and expression of the androgen receptor (AR). Endocrine therapy can be used for treatment of early stage androgen-responsive tumors, whereas chemotherapy for later stage androgen- nonresponsive tumors is problematic. We have investigated the aryl hydrocarbon receptor (AhR) as a potential target for treating prostate cancer using a new series of relatively non-toxic selective AhR modulators (SAhRMs). ... |
|
| Dynamics of Estrogen Receptor Transcription Complex Assembly in Breast Cancer |
JUL 2003 |
16 pages |
| Authors:
Eli V. Hestermann; DANA-FARBER CANCER INST BOSTON MA
|
| Estrogen plays a critical role in the development and progression of breast cancer. While endocrine therapies play an important part in breast cancer treatment, the failure of these therapies reflects a lack of knowledge concerning the molecular mechanisms involved in estrogen signaling. The biological activities of estrogen are mediated by estrogen receptors (ER) . In addition, a large number of proteins termed cofactors are involved in ER signaling. Until recently, ... |
|
| Melatonin Aging and Breast Cancer |
JUN 2003 |
16 pages |
| Authors:
Steven M. Hill; TULANE UNIV NEW ORLEANS LA SCHOOL OF MEDICINE
|
| The pineal gland, via its hormone melatonin, inhibits the proliferation of both human and animal models of breast cancer. As humans age there is the onset of disrupted sleep leading to a significant suppression in the nocturnal levels of melatonin after age 60. We have hypothesized that the decline in pineal melatonin production, with the onset of old age, is a key factor in the age-related increase in breast cancer. ... |
|
| Definition of the Molecular Mechanisms Which Distinguish Between Selective Estrogen Receptor Modulators (SERMs) and Full Antiestrogens |
MAY 2003 |
12 pages |
| Authors:
Huey-Jing Huang; DUKE UNIV MEDICAL CENTER DURHAM NC
|
| Tamoxifen, a SERM (Selective Estrogen Receptor Modulator), is the most commonly used endocrine treatment for all stages of breast cancer. However, progression from tamoxifen sensitivity to tamoxifen resistance occurs in a substantial portion of the tumors. Full antiestrogens, such as ICI 182,780, are currently used as the second line therapy after failure of long-term tamoxifen therapy. To facilitate the design and characterization of more appropriate therapeutic agents for endocrine therapy ... |
|
| Identification of Signaling Proteins That Modulate Androgen Receptor Activity |
MAY 2003 |
7 pages |
| Authors:
Zhou Songyang; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Androgens and the androgen receptor (AR) play a critical role in the development and progression of prostate cancers. The majority of prostate cancers initially respond to endocrine treatment (androgen dependent), but eventually become androgen independent that prove fatal. It appears that a functionally active AR may contribute to the progression of androgen-independent prostate cancers. Understanding the signaling pathways that regulate androgen- dependent and -independent activation of AR mediated transcription would ... |
|
| Molecular Markers of Estrogen Metabolism and Progression From High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) to Prostate Cancer |
MAR 2003 |
92 pages |
| Authors:
Jay H. Fowke; Fritz Parl; Quiyin Cai; Scott Shappell; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| The purpose of this case-control study is to investigate the association between genetic and endocrine markers of estrogen metabolism and prostate cancer progression. Androgens (e.g., testosterone) may be critical in prostate cancercinogenesis, but there is accumulating evidence that estrogens facilitate progress during the later stages of prostate cancer formation (1-4). To explore the role of estrogens in human prostate carcinogenesis, we proposed to investigate the association between genetic and endocrine ... |
|
| Inhibitory Ah Receptor - Androgen Receptor Crosstalk in Prostate Cancer |
FEB 2003 |
26 pages |
| Authors:
Stephen Safe; TEXAS A AND M RESEARCH FOUNDATION COLLEGE STATION
|
| Treatment for prostate cancer depends on multiple factors including the stage of the tumor and expression of the androgen receptor (AR) Endocrine therapy can be used for treatment of early stage androgen-responsive tumors, whereas chemotherapy for later stage androgen- nonresponsive tumors is problematic We have investigated the aryl hydrocarbon receptor (AhR) as a potential target for treating prostate cancer using a new series of relatively non-toxic selective AhR modulators (SAhRMs). ... |
|
| Progesterone Receptor Isoform Influence on Human Breast Tumor Growth and Hormone Treatment |
JAN 2003 |
30 pages |
| Authors:
Carol A. Sartorius; COLORADO UNIV AT FITZSIMMONS AURORA HEALTH SCIENCES CENTER
|
| Many postmenopausal women receive progestins in conjunction with estrogens as part of hormone replacement therapy. These women have a slightly higher risk of developing breast cancer than those receiving estrogen alone Progesterone mediates its affects through two known forms of the progesterone receptor, PR-A and PR-B. We aim to study how progesterone, via either PR-A or PR-B, influences estrogen-stimulated tumor formation and growth. |
|
| Psycho-Endocrine-Immune Profile: Implications for Quality of Life in Breast Cancer Patients |
NOV 2002 |
83 pages |
| Authors:
Linda J. Janusek; LOYOLA UNIV MAYWOOD IL
|
| Biopsy of the breast for cancer diagnosis is an emotional experience, characterized by anxiety and fear. This experience may impair immune responses. This study evaluated a woman's immunological and psychological response pre and post breast biopsy. Perceived stress, anxiety, and mood disturbance were heightened pre-biopsy. Post-biopsy; perceived stress, anxiety, and mood disturbance decreased but did not return to levels reported by non-biopsied control women. Natural killer (NK) cell activity was ... |
|
| A Laboratory Comparison of Clockwise and Counter-Clockwise Rapidly Rotating Shift Schedules, Part III: Effects on Core Body Temperature and Neuroendocrine Measures |
NOV 2002 |
20 pages |
| Authors:
Albert Boquet; Crystal E. Cruz; Thomas E. Nesthus; Cristy A. Detwiler; William R. Knecht; Kali A. Holcomb; FEDERAL AVIATION ADMINISTRATION OKLAHOMA CITY OK CIVIL AEROMEDICAL INST
|
| Most researchers suggest that shift rotation in a forward or clockwise direction produces less disruption of circadian rhythms than those that rotate in a backward or counter-clockwise direction. This is based upon extrapolation from quasi-experimental studies of shift-workers and research on the effects of jet lag, which indicate that westward travel results in less disruption of circadian rhythms. The effect of direction of rotation on cortisol, melatonin, and core body ... |
|
| ER/AP-1 Modifications in Tamoxifen-Resistant Human Breast Tumors |
SEP 2002 |
16 pages |
| Authors:
Jose E. Meza; Christopher C. Benz; CALIFORNIA UNIV SAN FRANCISCO
|
| Endocrine therapy in the form of aromatase inhibitors or antiestrogens like tamoxifen is the treatment of choice for most patients with estrogen receptor (ER)-positive breast cancers. However, it remains unclear why up 30-50% of ER-positive tumors demonstrate clinical resistance to these forms of ER-targeted treatments. It is known that ER that is structurally altered such that it cannot bind directly to its ERE, can still affect gene expression via protein-protein ... |
|
| Dynamics of Estrogen Receptor Transcription Complex Assembly in Breast Cancer |
JUL 2002 |
23 pages |
| Authors:
Eli Hesterman; Myles A. Brown; Yongfeng Shang; DANA-FARBER CANCER INST BOSTON MA
|
| Estrogen plays a critical role in the development and progression of breast cancer. While endocrine therapies play an important part in breast cancer treatment, the failure of these therapies reflects a lack of knowledge concerning the molecular mechanisms involved in estrogen signaling. The biological activities of estrogen are mediated by estrogen receptors (ER) . In addition, a large number of proteins termed cofactors are involved in ER signaling. Until recently, ... |
|
| Cyclin D1 and Cyclin E as Markers of Therapeutic Responsiveness in Breast Cancer |
MAY 2002 |
|
| Authors:
Rina Hui; Robert L. Sutherland; GARVAN INST OF MEDICAL RESEARCH SYDNEY (AUSTRALIA)
|
| Cyclin Dl and cyclin E are overexpressed in approximately 43% and 30% of breast cancer and overexpression of these two oncogenes is associated with poor prognosis. To define the role of cyclin Dl and cyclin E expression as markers of therapeutic responsiveness, cell lines overexpressing cyclin Dl or cyclin E were produced. Constitutive overexpression of cyclin Dl in the range of 5 fold and cyclin E in the range of ... |
|
| Identification of Signaling Proteins that Modulate Androgen Receptor Activity |
MAY 2002 |
6 pages |
| Authors:
Zhou Songyang; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Androgens and the androgen receptor (AR) play a critical role in the development and progression of prostate cancers. The majority of prostate cancers initially respond to endocrine treatment (androgen dependent) but eventually become androgen independent that prove fatal. It appears that a functionally active AR may contribute to the progression of androgen-independent prostate cancers. Understanding the signaling pathways that regulate androgen- dependent and independent activation of AR mediated transcription would ... |
|
| Psycho-Endocrine-Immune Profile: Implications for Quality of Life in Breast Cancer Patients |
NOV 2001 |
113 pages |
| Authors:
Linda J. Janusek; LOYOLA UNIV MAYWOOD IL
|
| Biopsy of the breast for cancer diagnosis is an emotional experience, characterized by anxiety and fear. This experience may impair immune responses. This study evaluated a woman's immunological and psychological response pre and post breast biopsy. Perceived stress, anxiety, and mood disturbance were heightened pre-biopsy. Post-biopsy; perceived stress, anxiety, and mood disturbance decreased but did not return to levels reported by non-biopsied control women. Natural killer (NK) cell activity was ... |
|
| Targeting of the Hepatocyte Growth Factor Pathway for the Treatment for Breast Cancer |
SEP 2001 |
23 pages |
| Authors:
Jill M. Siegfried; PITTSBURGH UNIV PA
|
| Hepatocyte growth factor (HCF), also known as Scatter Factor, induces cell growth and cell movement, and is known to promote invasiveness of malignant cells. It also promotes angiogenesis. HGF is known to be produced by fibroblasts within breast tumors, while its receptor, the c-Met protein, is expressed on the breast tumor cells themselves. HGF thus appears to act predominantly as a paracrine factor in breast cancer. High levels of HGF ... |
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| An Estrogen Receptor-Selective Coactivator: A Potential Regulator of Tamoxifen Effectiveness in Breast Cancer Treatment and Prevention |
SEP 2001 |
15 pages |
| Authors:
Ramji R. Rajendran; ILLINOIS UNIV CHAMPAIGN
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| Much evidence demonstrates that the estrogen receptor (ER) is involved in breast cancer development and progression. We have isolated a novel 97 kDa DEAD box RNA helicase protein (p97), from breast cancer cells, which interacts with the estrogen receptor E and F domains in the presence of either estradiol or trans-hydroxytamoxifen. We have further confirmed the interaction of p97 with ER using both GST-pulldown analysis and a mammalian two-hybrid assay. ... |
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