| Epigenetic Programming of Breast Cancer and Nutrition Prevention |
MAY 2011 |
20 pages |
| Authors:
Donato Romagnolo; ARIZONA UNIV TUCSON
|
 | The purpose of this project is to investigate whether epigenetic mechanisms may contribute to reduced expression of the tumor suppressor gene BRCA-1 in sporadic breast cancers. The scope is to test the role of xenobiotics and food compounds that bind the aromatic hydrocarbon receptor (AhR). AhR-ligands include the dioxin-like and tumor promoter 2,3,7,8 tetrachlorobenzo-p-dioxin (TCDD). The activated AhR regulates transcription through binding to xenobiotic response elements (XRE=GCGTG) and interactions with ... |
|
| Oxidative Lung Injury in Virus-Induced Wheezing |
May 2011 |
20 pages |
| Authors:
Roberto P Garofalo; TEXAS UNIV AT GALVESTON
|
| This project focuses on respiratory syncytial virus (RSV), the single most important pathogen causing acute respiratory-tract infections in children. RSV infections are a major precipitating factor of wheezing in asthmatic children, and they have been linked to both the development and the severity of asthma. Our group has established a multidisciplinary and highly integrated pre-clinical and translational research program that focuses on the role of oxidative injury in the pathogenesis ... |
|
| Elucidating Mechanisms of Farnesyltransferase Inhibitor Action and Resistance in Breast Cancer by Bioluminescence Imaging |
30 JUN 2010 |
10 pages |
| Authors:
David Piwnica-Worms; WASHINGTON UNIV ST LOUIS MO
|
| Prenyltransferase inhibitors (FTIs & GGTIs) block post-translational processing of Ras-like GTPases that have key roles in breast cancer. However, FTIs have yet to be used widely in breast cancer therapy because it is not yet possible to identify patients likely to be FTI-sensitive or to use combinatorial therapy to broaden the spectrum of patients that respond to FTIs. A new lentiviral-based prenylation responsive bioluminescence reporter system has been constructed and ... |
|
| Epigenetic Characterization of Ovarian Cancer |
Dec-2008 |
105 pages |
| Authors:
Susan K Murphy; DUKE UNIV MEDICAL CENTER DURHAM NC
|
| The overall objective of this research was to identify genes that are aberrantly methylated in epithelial ovarian cancer. Our approach was to treat or mock treat primary normal or tumor cultured cells with drugs that inhibit DNA methyltransferase activity and then perform microarray analysis to identify genes that are likely to exhibit methylation-mediated silencing. We also employed similar analysis of 43 ovarian cell lines. Two major criteria identified genes likely ... |
|
| Functional Characterization and Expression of Molluscan Detoxification Enzymes and Transporters Involved in Dietary Allelochemical Resistance |
01-Jun-2008 |
|
| 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 ... |
|
| A Transgenic Model for Learning Defects: Role of NF1 in Drosophila Visuospatial Learning |
Jun-2008 |
12 pages |
| Authors:
Frances Hannan; NEW YORK MEDICAL COLL VALHALLA
|
| Learning difficulties and attention deficits are observed in 40-50% of children with Neurofibromatosis Type 1 (NF1). Additionally many NFI patients exhibit specific deficits in visuo-spatial tasks such as the Judgment of Line Orientation task. Spatial learning is also disrupted in heterozygous mouse Nf1 mutants and can be rescued by reducing Ras activity either genetically or pharmacologically. Conversely olfactory learning defects observed in Nf1 mutant fruit flies are cAMP-dependent rather than ... |
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| The Role of HOX Proteins in Androgen-Independent Prostate Cancer |
NOV 2007 |
9 pages |
| Authors:
Sunshine Daddario; COLORADO UNIV AURORA CO
|
| HOX genes encode a large family of transcription factors involved in key developmental decisions, and are often aberrantly expressed in cancer. Our laboratory has previously shown that a subset of genes of the HOXC cluster are overexpressed in primary prostate tumors, metastases, and prostate cancer (PCa) cell lines. Increasing transient expression of HOXC8 in LNCaP PCa cells as well as HPr-1 AR non-tumorigenic prostate epithelial cells results in a progressive ... |
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| Detection of Metastatic Potential in Breast Cancer by RhoC-GTPase and WISP3 Proteins |
MAY 2007 |
58 pages |
| Authors:
Celina G. Kleer; MICHIGAN UNIV ANN ARBOR
|
| Breast cancer is the most common type of life-threatening cancer, and the second most common cause of cancer related deaths of women in the United States. Even though the larger the primary tumor, the greater the likelihood of metastases, this is not always the case. There are many small breast cancers with a highly aggressive and metastatic behavior and discouraging outcome that remain under treated because there is no marker ... |
|
| Chromatin Structure and Breast Cancer Radiosensitivity |
01 OCT 2006 |
10 pages |
| Authors:
Tej K. Pandita; WASHINGTON UNIV ST LOUIS MO
|
| The hMOF protein is a chromatin-modifying factor. Chromatin structure plays a critical role in gene expression. Since hMOF has a chromodomain region as well as acetyl transferase activity, its inactivation can influence modification of chromatin during DNA metabolism. The proposed experiments of this grant proposal will determine functions of hMOF gene. This will be achieved by generating isogenic cells with and without hMOF function. Both in vivo and in vitro ... |
|
| Prostate Cancer Detection by Molecular Urinalysis |
APR 2006 |
8 pages |
| Authors:
Christian P. Pavlovich; David Y. Chan; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death in the United States. The most common DNA alteration associated with prostate cancer is hypermethylation in the regulatory region of certain genes, particularly in the promoter of the pi-class glutathione-S-transferase (GSTP1) gene. Analysis of hypermethylation of other gene promoters in combination has demonstrated high sensitivity and specificity for prostate cancer diagnosis. In this project, ... |
|
| Pretreatment of Human Epidermal Keratinocytes with D,L-Sulforaphane Protects Against Sulfur Mustard Cytotoxicity |
2006 |
10 pages |
| Authors:
Clark L. Gross; Eric W. Neally; Mary T. Nipwoda; William J. Smith; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| Sulfur mustard (SM) is a powerful cytotoxic agent as well as a potent vesicant, mutagen, and carcinogen. This compound reacts with glutathione (GSH) and forms GSH-SM conjugates that appear to be excreted through the mercapturic acid pathway in mammals. The question of whether glutathione-S-tranferases (GST) are involved in enzymatic formation of these conjugates remains unresolved In previous studies, ethacrynic acid (EAA), a putative inhibitor of this transferase, and oltipraz, a ... |
|
| Chromatin Structure and Breast Cancer Radiosensitivity |
OCT 2005 |
8 pages |
| Authors:
Tej K. Pandita; WASHINGTON UNIV ST LOUIS MO
|
| The hMOF protein is a chromatin-modifying factor. Chromatin structure plays a critical role in gene expression. Since hMOF has a chromodomain region as well as acetyl transferase activity its inactivation can influence modification of chromatin during DNA metabolism. The proposed experiments of this grant proposal will determine functions of hMOF gene. This will be achieved by generating isogenic cells with and without hMOF function. Both in vivo and in vitro ... |
|
| Detection of Metastatic Potential in Breast Cancer by RhoC-GTPase and WISP3 Proteins |
MAY 2005 |
15 pages |
| Authors:
Celina G. Kleer; MICHIGAN UNIV ANN ARBOR
|
| This is the third annual report for a project that aims at understanding the clinical utility of RhoC-GTPase and WISP3 proteins in breast cancer patients. These two genes were identified as key genetic determinants of inflammatory breast cancer (IBC). We believe that RhoC GTPase and WISP3 act in concert to determine a highly metastatic breast cancer phenotype, and that they may help identify which invasive breast carcinomas are aggressive from ... |
|
| Rho GTPase Involvement in Breast Cancer Migration and Invasion |
MAR 2005 |
23 pages |
| Authors:
Kaylene J. Simpson; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| The RhoGTPases play a critical role in cell migration via regulation of cytoskeletal changes. Increased expression of Rho proteins. in particular RhoC, have been associated with invasive carcinoma, however, the functional contributions of the individual isoforms have been difficult to evaluate due to insufficient molecular tools. We used a stable retroviral RNAi approach to abrogate expression of RhoA or RhoC in the SUM-159 invasive breast carcinoma cell line. We observed ... |
|
| Two New Plant-Like Pathways Link Hemoglobin Degradation to Lipid Biogenesis in Falciparum Malaria: Novel Targets for Anti-Malarial Chemotherapy |
MAR 2005 |
25 pages |
| Authors:
Choukri B. Mamoun; CONNECTICUT UNIV HEALTH CENTER FARMINGTON
|
| "Plasmodium falciparum" is the causative agent of the most severe form of human malaria. The rapid multiplication of the parasite within human erythrocytes requires an active production of new membranes. Phosphatidylcholine (PtdCho) is the most abundant phospholipid in "Plasmodium" membranes and the pathways leading to its synthesis are attractive targets for chemotherapy. In this report, the authors describe molecular and biochemical studies that provide evidence for the presence of a ... |
|
| Mechanisms to Detoxify Selected Organic Contaminants in Higher Plants and Microbes, and Their Potential Use in Landscape Management |
OCT 2004 |
144 pages |
| Authors:
George Kvesitadze; Gia Khatisashvili; Tinatin Sadunishvili; ACADEMY OF SCIENCES OF GEORGIA (TBILISI) DURMISHIDZE INST OF BIOCHEMISTRY AND BIOTECHNOLOGY
|
| In this report biochemical and physiological processes important for the phytoremediation of organic contaminants are discussed. Literature data on the uptake and potential of plants and microorganisms to detoxify organic contaminants are analyzed. Mechanisms of penetration and translocation of organic contaminants in plant leaves and roots are described. The principal transformation phases of organic contaminants once entered into a plant are: functionalization, conjugation and compartmentation. The following mechanisms to detoxify ... |
|
| Detection of Metastatic Potential in Breast Cancer by RhoC-GTPase and WISP3 Proteins |
MAY 2004 |
42 pages |
| Authors:
Celina G. Kleer; MICHIGAN UNIV ANN ARBOR
|
| Breast cancer is the most common type of life-threatening cancer, and the second most common cause of cancer related deaths of women in the United States. Even though the larger the primary tumor, the greater the likelihood of metastases, this is not always the case. There are many small breast cancers with a highly aggressive and metastatic behavior and discouraging outcome that remain under treated because there is no marker ... |
|
| Estrogen and Retinoid Regulation of DNA Repair in Breast Cancer |
MAY 2004 |
11 pages |
| Authors:
David L. Crowe; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| Chemotherapeutic agents used in the treatment breast cancer produce their cytotoxic effects by creating DNA damage. Estrogen (ER) and retinoic acid receptors (RAR) are members of a family of ligand dependent transcription factors. ER, RAR, and BRCAl require CREB binding protein (CBP) to activate target gene transcription. The application proposed a new mechanism by which ER and RAR regulate BRCAl mediated DNA repair via CBP. In the second year of ... |
|
| Mechanism of Transcriptional Regulation by Androgen Receptor and its Coactivators in the Context of Chromatin |
JAN 2004 |
62 pages |
| Authors:
Jiemin Wong; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Androgens play important roles in the differentiation, development and maintenance of male reproductive functions, as well as in the etiology of prostate cancer. The biological effects of androgens are believed to be mediated through the intracellular androgen receptor (AR), which belongs to the nuclear receptor (NR) superfamily of ligand-regulated transcription factors. Like other NRs, the actions of AR are subject to modulation, either positively or negatively, by an increasing number ... |
|
| Genistein Programming Against Breast Cancer |
SEP 2003 |
27 pages |
| Authors:
Coral A. Lamartiniers; ALABAMA UNIV IN BIRMINGHAM
|
| Most soy-breast cancer epidemiological studies conclude that Asian women consuming a traditional diet high in soy products have a low incidence of breast cancer. We have previously demonstrated that prepubertal exposure to genistein, the primary isoflavone of soy, protects against chemically-induced mammary cancer. The purpose of this work was to determine if adult exposure to genistein will protect against chemically-induced mammary cancer and to investigate DNA methylation of estrogen receptor ... |
|
| An Epigenetic Approach to Breast Cancer Treatment |
AUG 2003 |
67 pages |
| Authors:
Norbert R. Reich; CALIFORNIA UNIV SANTA BARBARA DEPT OF CHEMISTRY AND BIOCHEMISTRY
|
| DNA methylation is an epigenetic process that leads to normal and dysfunctional gene regulation. The latter is a well-documented pathway to tumorigenesis, particularly for certain tumors, such as those involved in breast cancer. We have identified several inhibitors of the mammalian DNA cytosine methyltransferase, and are trying to determine if such compounds are suitable for further development as cancer therapies. |
|
| Distribution of the Coenzyme M Pathway of Epoxide Metabolism Among Ethene- and Vinyl Chloride-Degrading Mycobacterium Strains |
09 JUL 2003 |
7 pages |
| Authors:
Nicholas V. Coleman; Jim C. Spain; SYDNEY UNIV (AUSTRALIA)
|
| An epoxyalkane:coenzyme M (CoM) transferase (EaCoMT) enzyme was recently found to be active in the aerobic vinyl chloride (VC) and ethene assimilation pathways of Mycobacterium strain JS6O. In the present study, EaCoMT activity and genes were investigated in 10 different mycobacteria isolated on VC or ethene from diverse environmental samples. In all cases, epoxyethane metabolism in cell extracts was dependent on CoM, with average specific activities of EaCoMT between 380 ... |
|
| Epoxyalkane: Coenzyme M Transferase in the Ethene and Vinyl Chloride Biodegradation Pathways of Mycobacterium Strain JS60 |
03 JUL 2003 |
11 pages |
| Authors:
Nicholas V. Coleman; Jim C. Spain; SYDNEY UNIV (AUSTRALIA) SCHOOL OF MOLECULAR AND MICROBIAL BIOSCIENCES
|
| Mycobacterium strains that grow on ethene and vinyl chloride (VC) are widely distributed in the environment and are potentially useful for biocatalysis and bioremediation. The catabolic pathway of alkene assimilation in mycobacteria is not well characterized. It is clear that the initial step is a monooxygenase-mediated expoxidation that produces epoxyethane from ethene and chlorooxirane from VC, but the enzymes involved in subsequent transformation of the epoxides have not been identified. ... |
|
| Detection of Metastatic Potential in Breast Cancer by RhoC-GTPase and WISP3 Proteins |
MAY 2003 |
43 pages |
| Authors:
Celina G. Kleer; MICHIGAN UNIV ANN ARBOR
|
| Breast cancer is the most common type of life-threatening cancer, and the second most common cause of cancer related deaths of women in the United States. Even though the larger the primary tumor, the greater the likelihood of metastases, this is not always the case. There are many small breast cancers with a highly aggressive and metastatic behavior and discouraging outcome that remain under treated because there is no marker ... |
|
| Molecular Determinants of Cellular Sensitivity to Flavopiridol, an Anti- Cell Signaling Anticancer Agent |
OCT 2002 |
46 pages |
| Authors:
Colin R. Campbell; MINNESOTA UNIV MINNEAPOLIS
|
| Flavopiridol is an investigational drug undergoing Phase II clinical trials for the treatment of various solid tumors. This drug has been shown to inhibit of the cyclin- dependent protein kinases, which are essential mediators of the cell division cycle. While this activity is likely to be responsible for its anticancer activity, it is nevertheless unclear how this drug achieves selective toxicity. To address this question, we created a flavopiridol- resistant ... |
|
| Tumor Suppressors and Breast Cancer |
OCT 2002 |
33 pages |
| Authors:
E. Shyam; P. Reddy; HAHNEMANN MEDICAL COLL OF PHILADELPHIA (MCP) PA
|
| Mutations in BRCA2 are responsible for about 35% of familial breast cancers and also a proportion of familial ovarian cancers. Both BRCA2 and BRCA1 proteins were shown to have transcriptional activation domains and also shown to be associated with RNA polymerase suggesting that these proteins may function as transcriptional factors and have a role in the regulation of transcription. Recent studies on enzymes responsible for histone acetylation and deacetylation revealed ... |
|
| Regulation of Tumor Progression by Mgat5-Dependent Glycosylation |
JUL 2002 |
51 pages |
| Authors:
James W. Dennis; MOUNT SINAI HOSPITAL TORONTO (ONTARIO)SAMUEL LUNENFIELD RESEARCH INST
|
| Task 1 was to further define the phenotype of Mgat5-/- cells regarding adhesion, signal transduction, and growth factor responsiveness. We have established immortalized embryonic fibroblast cell lines form Mgat5-/- mice, made Mgat5 retrovial vector for rescue of the mutant phenotypes, and established new technology (the Cellomics scan array system) to measure these parameters with precision. Task 2 was to use genetic methods to analysis Mgat5 dependent tumor progression in vivo. ... |
|
| Mechanism of Transcriptional Regulation by Androgen Receptor and its Coactivators in the Context of Chromatin |
JUL 2002 |
72 pages |
| Authors:
Jiemin Wong; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Androgens play important roles in the differentiation, development and maintenance of male reproductive functions as well as in the etiology of prostate cancer. The biological effects of androgens are believed to be mediated through the intracellular androgen receptor (AR), which belongs to the nuclear receptor (NR) superfamily of ligand-regulated transcription factors. Like other NRs, the actions of AR are subject to modulation, either positively or negatively, by an increasing number ... |
|
| Inhibition of Tumor cells that Over-Express nGST |
JUL 2002 |
86 pages |
| Authors:
Donald J. Creighton; MARYLAND UNIV BALTIMORE
|
| In the third and final year of this three year project, we have characterized 2crotonyl-oxymethyl-2- cyclohexenone (COMC-6) and its derivatives as substrates for human glutathione transferase (hGST), producing as products cytotoxic alkylating agents of nucleic acids and/or proteins critical to cell function. Compounds of this type should be potent antitumor agents against breast cancer cells over expressing GST as part of the multidrug resistance phenotype. Specifically, we have (a) discovered ... |
|
| Control of Metastasis-Associated Gene Expression by Cell-Surface Beta-1, 6 Branched Oligosaccharide Expression |
JUN 2002 |
10 pages |
| Authors:
William G. Chaney; NEBRASKA UNIV MEDICAL CENTER OMAHA
|
| Metastatic breast cancer cells express cell-surface Beta-1,6 branched oligosaccharide structures, which are reduced/absent in normal breast tissue. The biosynthesis at these structures is initiated by the Golgi-localized glycosyltransferase N-Acetylglucosamlnyl- transferase V (GlcNAc-T V). The altered expression or GlcNAc-T V in animal mammary cancer models also influences metastasis. Furthermore, altered transcription of metastasis- associated genes has also been observed in cells with a reduced expression at cell-surface Beta- l,6 branched oligosaccharide ... |
|
| Glutathione Transferase in the Decontamination of O-P Toxins and Chlorinated Hydrocarbons |
16 JAN 2002 |
5 pages |
| Authors:
Michael Syvanen; CALIFORNIA UNIV DAVIS SCHOOL OF MEDICINE
|
| Glutathione transferases are ubiquitous in nature. So far they have been found in all eukaryotes and most bacteria strongly implying they serve an essential function for life. This function appears to be no more than an aid to organisms to detoxify certain chemically active agents that can be toxic. In the housefly Musca domesitica we have been studying the gst gene and its encoded enzyme that is responsible for detoxifying ... |
|
| Characterization of the Contribution of Ceramide to Chemotherapy Sensitization in Breast Cancer Cells |
SEP 2001 |
43 pages |
| Authors:
Hongtao Wang; Myles C. Cabot; JOHN WAYNE INST FOR CANCER TREATMENT AND RESEARCH SANTA MONICA CA
|
| Our previous studies showed that PSC 833, the multidrug resistance modulator, increases cellular ceramide levels. Our studies in the first grant year demonstrated that PSC 833 increases ceramide levels via serine palmitoyl- transferase (SPT) activation. However, the effects of PSC 833 on other de novo enzymes, the scope of PSC 833/ceramide response in human breast cancer cells, and the extent to which other anticancer drugs impact SPT remain unknown. To ... |
|
| Regulation of Tumor Progression by Mgat5-Dependent Glycosylation |
JUL 2001 |
43 pages |
| Authors:
James W. Dennis; MOUNT SINAI HOSPITAL TORONTO (ONTARIO)SAMUEL LUNENFIELD RESEARCH INST
|
| Task 1 was to further define the phenotype of Mgat5(-/-) cells regarding adhesion, signal transduction, and growth factor responsiveness. We have established immortalized embryonic fibroblast cell lines form Mgat5(-/-) mice, made Mgat5 retrovial vector for rescue of the mutant phenotypes, and established new technology (the Cellomics scan array system) to measure these parameters with precision. Task 2 was to use genetic methods to analysis Mgat5 dependent tumor progression in vivo. ... |
|
| Inhibition of Tumor Cells that Over-Express nGST |
JUL 2001 |
60 pages |
| Authors:
Donald J. Creighton; MARYLAND UNIV BALTIMORE
|
| In the second year of this three year project, we have discovered an additional class of molecules that will serve as substrates for human glutathione transferase, producing as products cytotoxic alkylating agents of nucleic acids and/or proteins critical to cell function. This provides additional evidence that it is possible to make antitumor prodrugs that will selectively kill multidrug resistant breast cancer cells by using glutathione transferase as a drug factory ... |
|
| Mechanism of Transcriptional Regulation by Androgen Receptor and its Coactivators in the Context of Chromatin |
JUL 2001 |
32 pages |
| Authors:
Jiemin Wong; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Androgens play important roles in the differentiation, development and maintenance of male reproductive functions, as well as in the etiology of prostate cancer. The biological effects of androgens are believed to be mediated through the intracellular androgen receptor (AR), which belongs to the nuclear receptor (NR) superfamily of ligand-regulated transcription factors. Like other NRs, the actions of AR are subject to modulation, either positively or negatively, by an increasing number ... |
|
| Dissecting the Immunogenicity of Monoclonal Antibodies |
JUN 2001 |
11 pages |
| Authors:
Christopher M. Snyder; Lawrence J. Wysocki; NATIONAL JEWISH MEDICAL AND RESEARCH CENTER DENVER CO
|
| The potential of mononclonal antibodies, (mAbs), for use in therapeutic and diagnostic applications has not been fully realized in part due to counter-immune responses that often arise in patient recipients of mAb. A growing research effort to humanize mAb has focused primarily on the structure or sequence of the antibody variable (V) region domains. However, these approaches may ultimately suffer, as they overlook the requirement of T cell help for ... |
|
| Development of an Assay for Prostate Cancer Based on Methylation Status of Glutathione S-Transferase (p) |
MAR 2001 |
40 pages |
| Authors:
Jeffrey S. Ross; ALBANY MEDICAL COLL NY
|
| Glutathiaone-s-transferase (GST)-Pi gene is frequently methylated in prostate cancer and recent evidence has linked aberrant expression of this gene with the development of prostatic adenocarcinomas (PACs). The main purpose of this study is to evaluate GST-Pi protein expression by immunohistochemistry (IHC) and develop a simple DNA amplification assay for detection of GST-Pi methylation status. 220 cases including 180 PACs and 20 cases each of normal and benign hyperplastic tissues were ... |
|
| Multiplex PCR-Based Determination of Genetic Polymorphisms Involved in the Etiology of Breast Cancer |
SEP 2000 |
14 pages |
| Authors:
John R. Herron; Cosette Wheeler; NEW MEXICO UNIV ALBUQUERQUE
|
| Breast cancer incidence rates for New Mexico's women have risen rapidly over the last two decades, particularly in Hispanics for whom breast cancer mortality rates have doubled. Despite this fact, the causes of breast cancer in this minority population have not been adequately characterized; thus, hampering interventions to reverse these trends. We have proposed to develop novel methods to evaluate allelic polymorphisms potentially associated with breast and other forms of ... |
|
| The Role of DNA Methyltransferase in the Progression of Breast Cancer to a Hormone Independent Phenotype |
SEP 2000 |
43 pages |
| Authors:
Lan Yan; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOLOF MEDICINE
|
| Estrogen and progesterone and their receptors play major roles in the development and function of the mammary gland as well as in breast cancer biology and treatment. However, 25-30% of human breast cancers lack ER alpha and PR expression and respond poorly to hormonal treatment. Absence of ER alpha and PR expression is associated with lack of transcript, methylation of the CpG islands in the promoter regions of these genes, ... |
|
| Glutathione Transferases and the Multidrug Resistance - Associated Protein in Prevention of Potentially Carcinogenic Oxidant Stress in Breast Cancer |
JUN 2000 |
44 pages |
| Authors:
Robin Haynes; Alan Townsend; BOWMAN GRAY SCHOOL OF MEDICINE WINSTON-SALEM NC
|
| 4 HYDROXY 2 NONENAL IS A HIGHLY REACTIVE ALDEHYDE BYPRODUCT OF LIPID PEROXIDATION AND IS KNOWN TO BE HIGHLY CYTOTOXIC, DAMAGING BOTH DNA and protein. HNE has a unique structure which includes a lipid tail, and a polar head with an Cl aldehyde, a C3-C4 trans double bond, and a C4 hydroxy. By using compounds analogous in structure to HNE but lacking one individual component we have ... |
|
| Development of an Assay for Prostate Cancer Based on Methylation Status of Glutathione S-Transferase-pi |
MAR 2000 |
33 pages |
| Authors:
Jeffrey S. Ross; ALBANY MEDICAL COLL NY
|
| Prostate cancer is currently the most commonly diagnosed cancer in American men. Early diagnosis through accurate screening techniques will significantly contribute to the successful management and eventual eradication of this disease. Currently, serum PSA determination remains the cornerstone of prostate cancer screening. However, more accurate screening to better differentiate patients with benign disease from those with prostatic cancer will alleviate the unnecessary surgical procedures with a significant impact on patient ... |
|
| The Role of DNA Methyltransferase in the Progression of Breast Cancer of a Hormone Independent Phenotype |
SEP 1999 |
57 pages |
| Authors:
Sharyl J. Nass; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOLOF MEDICINE
|
| Investigating methylation events associated with estrogen receptor gene regulation will enhance our understanding of hormone resistance in breast cancer. Thus, studies were undertaken to examine the role of DNA methyl-transferase (DMT) in the progression of breast cancer to a hormone-insensitive phenotype. We have found that DMT protein levels tightly correlate with S phase fraction in ER-positive cells, whereas ER-negative cells express DMT throughout the cell cycle. Stable transfection of MCF7 ... |
|
| Glutathione Transferases and the Multidrug Resistance - Associated Protein in Prevention of Potentially Carcinogenic Oxidant Stress in Breast Cancer |
JUN 1999 |
52 pages |
| Authors:
Robin L. Haynes; BOWMAN GRAY SCHOOL OF MEDICINE WINSTON-SALEM NC
|
| The purpose of this project is to determine: a) mechanisms of toxicity or DNA damage by 4-hydroxy-nonenal (FINE), an oxidative stress-induced lipid aldehyde, and b) the protective functions of several key cellular enzymes against FINE and other potentially carcinogenic redox-active electrophiles. The focus is on the application of transgenic cell lines that express specific protective genes. The findings to date are: 1) the most efficient ... |
|
| The Relationship between Protein Structure and Function: a Comprehensive Survey with Application to the Yeast Genome |
1999 |
47 pages |
| Authors:
Hedi Hegyi; Mark Gerstein; YALE UNIV NEW HAVEN CT DEPT OF MOLECULAR BIOPHYSICS AND BIOCHEMISTRY
|
| For most proteins in the genome databases, function is predicted via sequence comparison. In spite of the popularity of this approach, the extent to which it can be reliably applied is unknown. We address this issue by systematically investigating the relationship between protein function and structure. We focus initially on enzymes classified by the Enzyme Commission (EC) and relate these to structurally classified proteins in the SCOP database. We find ... |
|
| The Relationship Between Protein Structure and Function: A Comprehensive Survey Focusing on Enzymes |
1999 |
20 pages |
| Authors:
Hedi Hegyi; Mark Gerstein; YALE UNIV NEW HAVEN CT DEPT OF MOLECULAR BIOPHYSICS AND BIOCHEMISTRY
|
| For most proteins in the genome databases, function is predicted via sequence comparison. In spite of the popularity of this approach, the extent to which it can be reliably applied is unknown. We address this issue by systematically investigating the relationship between protein function and structure. We focus initially on enzymes classified by the Enzyme Commission (EC) and relate these to structurally classified proteins in the SCOP database. We find ... |
|
| The Effect of DNA Methylation on IGF2 Expression |
SEP 1998 |
8 pages |
| Authors:
Kevin J. Cullen; GEORGETOWN UNIV WASHINGTON DC
|
| Our hypothesis is that DNA methyl transferase expression is inversely correlated with IGF-II expression in normal and tumor tissues. That is, tumors with high DNA methyl transferase expression will imprint IGF-II, resulting in reduced IGF-II expression, while tumors with low DNA methyl transferase will have higher relative IGF-II expression. We have demonstrated that DNA methyl transferase expression can be measured readily using RNase protection assay in ... |
|
| Novel Bioprocess for Polymer Synthesis and Assembly of New Materials |
15 APR 1998 |
14 pages |
| Authors:
Kenneth A. Marx; Richard Gross; Steve McCarthy; Changmo Sung; MASSACHUSETTS UNIV LOWELL
|
| The theme and purpose of the grant research was to investigate a number of new ways in which biological processes could be utilized to create new polymeric materials. In the various funded subsections of the grant, there were a number of separate areas of investigation, each studied by a cluster of investigators. The individual areas were: (1) Synthesis and characterization of polymeric materials enzymatically and chemically, incorporating biological macromolecules, in ... |
|
| Glutathione Transferase in the Decontamination of OP Toxins and Chlorinated Hydrocarbons |
30 APR 97 |
|
| Authors:
Michael Syvanen; CALIFORNIA UNIV DAVIS
|
| The enzyme glutathione transferase degrades organophosphate (OP) triester insecticides. Our research is targeted toward developing these enzymes for their use in nerve gas decontamination technology. To this end, progress has been made in the following areas: (1) Genes and enzymes have been characterized and sequenced from the housefly. (2) the genomic loci of those genes responsible for OP resistant housefly mutants have been partially characterized. (3) Work is progressing on ... |
|
| The Tumor Suppressor Protein p53 and its Physiological Splicing Variant p53 as in a Mouse Mammary Cancer Model |
OCT 96 |
38 pages |
| Authors:
Molly Kulesz-Martin; HEALTH RESEARCH INC BUFFALO NY
|
| Cellular and molecular aspects of p53 and an alternatively spliced protein, p53as, are being examined during cancer progression in both a mouse mammary and epidermal model. We report here that both p53 and p53as are expressed in cell lines and tissues of the mouse mammary model and, as previously reported, in epidermal cells. The half life of both proteins has been determined in asynchronous cells from both model systems. In ... |
|
| Statistical Process Control and Medical Surveillance. An Application with Liver Function Tests |
MAR 96 |
68 pages |
| Authors:
Bryan D. Richardson; AIR FORCE INST OF TECH WRIGHT-PATTERSON AFB OH
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| Traditionally, medical surveillance of liver disease generally involves a battery of tests. This research used multivariate analysis techniques to reduce the number of measures required to identify liver dysfunction and found using a Transferase Index (a combination of three tests; ALT, AST, and GGT) provided the most satisfying assessment, but the single best indicator, ALT, may be sufficient. Transferase Index and ALT criterion were both applied to SPC control charts. ... |
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