| Laminin-5 gamma2 Chain in Breast Cancer Metastasis |
Feb-2009 |
10 pages |
| Authors:
Shanshan Liu; VANDERBILT UNIV NASHVILLE TN
|
 | To metastasize, cancer cells have to break through the basement membrane. Ln-5 is one o f the basement membrane proteins, consisting of three chains a3,B3 and y2. Ln-5 y2 chain continas DIII domain, a functional EGFR ligand, which can be released by MMP processing. It has been suggested by our lab that DIII domain may facilitate cancer progression by preventing anoikis. However, both the increased and decreased expression levels of ... |
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| Applications of GIS, Advanced Sensors and Habitat Modeling in Support of Desert Tortoise Line Distance, Sampling and Translocation Studies Related to the Proposed Expansion of the Ft. Irwin NTC |
25-Sep-2008 |
29 pages |
| Authors:
Jordan Henk; REDLANDS UNIV CA
|
| This University of Redlands (University) research program (the Desert Tortoise Project; DTP), was designed to improve terrestrial science and to explore and apply a variety of information science technology, tools, and methods to equip land managers, decision-makers and policy-makers with science-based alternatives for the recovery of the desert tortoise (Gopherus agassizii, federally-listed in 1990 as a threatened species) within the West Mojave Recovery Unit (WMRU) of Southern California, and specifically, ... |
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| Inhibition of Rac GTPases in the Therapy of Chronic Myelogenous Leukemia |
01-Apr-2008 |
77 pages |
| Authors:
CHILDREN'S HOSPITAL MEDICAL CENTER CINCINNATI OH
|
| Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease (MPD) characterized by the expression of the p210-BCR/ABL fusion gene [1]. This gene is produced by the reciprocal translocation (9; 22) (q34; q11) that juxtaposes the 3 end of Abelson leukemia virus (ABL) gene with the 5 end of the breakpoint cluster region (Bcr) gene on chromosome 22. The transcript formed as a result encodes for the BCR/ABL fusion protein with ... |
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| Structural Studies on Toxins and Virulence Factors of Yersinia pestis |
Feb-2008 |
12 pages |
| Authors:
Subramanyan Swaminathan; BROOKHAVEN NATIONAL LAB UPTON NY
|
| In this final report we present our efforts on two or three fronts. We were working on the expression purification and crystallization of complexes of YopB and YopD with other proteins like their chaperones. We have made progress in purifying YopB:YopD:SycD complex. However this is a challenging process and the amount of homologous protein is a problem. Since the expression levels of different components of the complex are different the ... |
|
| Yersinia pestis YopD 150-287 Fragment is Partially Unfolded in the Native State |
17 NOV 2007 |
10 pages |
| Authors:
Ronald Raab; Wieslaw Swietnicki; JAMES MADISON UNIV HARRISONBURG VA
|
| Yersinia pestis is a human and animal pathogen uses the type III secretion system (TTSS) for delivering virulence factors and effectors into the host cells. The system is conserved in animal pathogens and is hypothesized to deliver the virulence factors directly from bacterial to mammalian cells through a pore composed of YopB and YopD translocation proteins. The YopB and YopD effector proteins must be delivered first to form a functional ... |
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| A New Concept for Androgen Receptor-Independent Growth of Prostate Cancer |
NOV 2007 |
11 pages |
| Authors:
Guo-fu Hu; Hiroko Kishikawa; Norie Yoshioka; HARVARD MEDICAL SCHOOL BOSTON MA
|
| Angiogenin is progressively upregulated in prostate cancer, in particular in androgen-independent diseases. The objective of this project is to explore the role angiogenin plays in the development of androgen-independent disease. In this reporting period, we have demonstrated that nuclear translocation of angiogenin is specific for prostate cancer cells and does not occur in normal prostate epithelial cells. Angiogenin is translocated to the nucleus of androgen-dependent cells (LNCaP) only when the ... |
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| Smad Acetylation: A New Level of Regulation in TGF-Beta Signaling |
JUL 2007 |
24 pages |
| Authors:
Andrea W. Tu; CALIFORNIA UNIV BERKELEY
|
| The transforming growth factor (TGF) signaling pathway is an essential pathway whose initiation results in cell growth arrest in most epithelial cells. Activation of TGF receptors leads to the phosphorylation and translocation of the Smad proteins, the major TGF intracellular signaling molecule, to the nucleus where transcription of TGF target genes occur. Many breast cancers contain aberrations in the regulation of Smad proteins demonstrating the importance of TGF signaling. Therefore, ... |
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| Differential Requirement for the Translocation of Clostridial Binary Toxins: Iota Toxin Requires a Membrane Potential Gradient |
28 FEB 2007 |
11 pages |
| Authors:
Maryse Gibert; Jean Marvaud; Yannick Pereira; Martha L. Hale; Bradley G. Stiles; Patrice Boquet; Christophe Lamaze; Michel R. Popoff; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Clostridial binary toxins, such as Clostridium perfringens Iota and Clostridium botulinum C2, are composed of a binding protein (Ib and C2-II, respectively) that recognizes distinct membrane receptors and mediates internalization of a catalytic protein (Ia and C2-I, respectively) with ADP-ribosyltransferase activity that depolymerizes the actin cytoskeleton. After internalization, it was found that C2 and Iota toxins were not routed to the Golgi apparatus and exhibited differential sensitivity to inhibitors of ... |
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| Properties of Leukemia Stem Cells in a Novel Model of CML Progression to Lymphoid Blast Crisis |
OCT 2006 |
9 pages |
| Authors:
Craig T. Jordan; ROCHESTER UNIV NY
|
| Progression of CML from chronic phase to lymphoid blast crisis is a poorly characterized event. However, at least some of the molecular events that accompany evolution of the disease have been described. One such event, mutation of the p16Ink4a/p19Arf locus, is known to occur in approximately 50% of patients developing acute lymphoid disease. Based on this observation, we generated a novel mouse model in which combination of the well-known BCR/ABL ... |
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| Identification of a Potent Apoptotic Peptide Produced by Fibroblasts; Studies Towards the Design of a Novel Agent for Breast Cancer Therapy |
01 SEP 2006 |
11 pages |
| Authors:
Lisa M. Petti; ALBANY MEDICAL COLL NY
|
| We previously showed that constitutive activation of the platelet-derived growth factor beta receptor (PDGFR) in mortal human fibroblasts (HDFs) by the bovine papillomavirus E5 or the v-Sis oncoprotein induces partial transformation of these cells. However, two weeks after they reach their peak density E5- and v-Sis-expressing HDFs secrete a small, hydrophilic peptide that induces massive apoptosis in an autocrine manner. Specifically, this peptide induces a type of caspase-independent, Bcl-2-resistant apoptosis ... |
|
| Combinatorial Strategies and High Throughput Screening in Drug Discovery Targeted to the Channel of Botulinum Neurotoxin |
01 SEP 2006 |
16 pages |
| Authors:
Mauricio Montal; CALIFORNIA UNIV SAN DIEGO LA JOLLA
|
| The ultimate goal of this program is to discover selective and potent drugs targeted to prevent or relieve the neurotoxic actions of botulinum neurotoxin (BoNT) A. A major goal of this program is the identification of open channel blockers as a single class of drugs that would be effective against all BoNT isoforms. We consider the BoNT channel as a validated target for intervention aimed to inhibit the translocation of ... |
|
| Mouse Model of Human Breast Cancer Initiated by a Fusion Oncogene |
SEP 2006 |
14 pages |
| Authors:
Stuart H. Orkin; CHILDREN'S HOSPITAL CORP BOSTON MA
|
| In this study, we generated a novel mouse model of human breast cancer based on a recurrent chromosomal translocation that produces the TEL-NTRK3 fusion oncogene, as the initiating mutation in human secretory breast carcinoma. In this model, we created a Ore-lox conditional knockin allele (TN) to express the TN fusion protein from the endogenous Tel locus in a tissue-specific manner. When TN is activated in mammary glands by whey acidic ... |
|
| Structural Studies on Toxins and Virulence Factors of Yersinia Pestis |
JUL 2006 |
11 pages |
| Authors:
S. Swaminathan; BROOKHAVEN NATIONAL LAB UPTON NY
|
| In this annual report we present our continuing efforts on two or three fronts. We are working on the expression purification and crystallization of complexes of YopB and YopD with other proteins like their chaperones. We have made progress in purifying YopB:YopD:SycD complex. If successful this will help in understanding the translocation mechanism of effector proteins. Our crystallization efforts on YopH and SycD are continuing. |
|
| Met Nuclear Localization and Signaling in Breast Cancer |
MAY 2006 |
18 pages |
| Authors:
Sharon P. Moulis; YALE UNIV NEW HAVEN CT
|
| Some breast cancer cases in our previous immunohistochemical studies show Met expression in the nucleus. Given nuclear localization of other receptor tyrosine kinases, we proceeded to investigate Met. Nuclear Met is seen in numerous cell lines and in germinal regions of many tissues using 4 unique antibodies. Cell fractionation reveals a 60kDa band recognized by C-terminal Met antibodies that is present independent of HGF treatment. GFP fusion proteins of the ... |
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| Expression and Cellular Internalization of Two Tat-Conjugated Fluorescent Proteins |
APR 2006 |
11 pages |
| Authors:
James P. Apland; Randall Kincaid; George Oyler; Michael Adler; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| Two hybrid vectors were designed for the expression in E. coli of fluorescent fusion proteins containing the protein translocation domain designated as Tat. The Tat domain was introduced to promote the entry of cargo protein, in this case the fluorophore yellow fluorescent protein (YFP), into cells. The first construct was made by fusing Tat with YFP. The second Tat fusion protein was constructed to contain YFP and the palmitoylation domain ... |
|
| An Exploration of the Effects of Genetic Drift on the Endangered Red-Cockaded Woodpecker |
MAR 2006 |
140 pages |
| Authors:
Ryan E. Nelson; AIR FORCE INST OF TECH WRIGHT-PATTERSON AFB OH SCHOOL OF ENGINEERING AND MANAGEMENT
|
| The Red-cockaded Woodpecker (RCW) (Picoides borealis) is classified as an endangered species under the Endangered Species Act of 1973 due to habitat fragmentation and prescribed burn suppression. Given the endangerment of the RCW, the genetic variation of the small populations will decrease over time due to random genetic drift. The only method of battling the negative effects of random genetic drift is to move, or translocate, genetically diverse birds into ... |
|
| Effects of Hematopoietic Stem Cell Age on CML Disease Progression |
MAR 2006 |
9 pages |
| Authors:
Kenneth Dorshkind; CALIFORNIA UNIV LOS ANGELES
|
| CML results from a chromosomal translocation in hematopoietic stem cells (HSC), yet the disease primarily presents as a myeloid hyperplasia with relatively infrequent lymphoid involvement. We proposed that age-associated defects in the potential of HSC to generate lymphocytes underlies this presentation. The results at the time of this writing support this hypothesis. Bone marrow cells from young and old mice were transduced with a retrovirus carrying the BCR-ABL 9:22 chromosomal ... |
|
| Single Molecule Detection Using a Silicon Nanopore-Nanotransistor Integrated Circuit |
JAN 2006 |
14 pages |
| Authors:
G. Timp; Jean-Pierre Leburton; Narayana Aluru; Klaus Schulten; Maria Gracheva; Alek Aksimentiev; Jiunn Heng; Val Dimitrov; Oelena Dimauro; ILLINOIS UNIV AT URBANA
|
| The focus of program was the production and testing of the transducer that consists of a nanopore Integrated with a MOSFET amplifier. The essential component is a single, nanometer-diameter pore in a robust, nanometer-thick membrane formed from a Metal Oxide Semiconductor (MOS) capacitor about 2 micrometers on edge. When an electric field is applied across the membrane immersed in electrolyte, a polyanion (like DNA) injected at the negative electrode is ... |
|
| Identification of a Potent Apoptotic Peptide by Fibroblasts: Studies Toward the Design of a Novel Agent for Breast Cancer Therapy |
SEP 2005 |
5 pages |
| Authors:
Lisa M. Petti; ALBANY MEDICAL COLL NY
|
| We previously showed that constitutive activation of the platelet-derived growth factor beta receptor (PDGFR) in mortal human fibroblasts (HDFs) by the bovine papillomavirus E5 or the v-Sis oncoprotein induces partial transformation of these cells. However, two weeks after they reach their peak density E5- and v-Sis-expressing HDFs secrete a small, hydrophilic peptide that induces massive apoptosis in an autocrine manner. Specifically, this peptide induces a type of caspase-independent, Bcl-2-resistant apoptosis ... |
|
| Characterization of a Plasmid-Encoded Type IV Secretion System in Campylobacter jejuni 81-176 |
17 AUG 2005 |
128 pages |
| Authors:
Joseph Larsen; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF MICROBIOLOGY AND IMMUNOLOGY
|
| The Gram-negative bacterium Campylobacter jejuni is major cause of diarrheal illness in both the United States and the world abroad. One strain of C. jejuni, 81-176, is a particularly virulent strain that invades epithelial cells at levels higher than most C. jejuni isolates. This strain possesses two plasmids, designated pVir and pTet, both of which contain genes with homology to type IV secretion systems (TFSS). TFSS are systems capable of ... |
|
| An Epithelial-Derived, Integral Membrane, Kunitz-Type Serine Protease Inhibitor in Breast Cancer |
AUG 2005 |
19 pages |
| Authors:
Chen-Yong Lin; GEORGETOWN UNIV WASHINGTON DC
|
| HAI-1 was initially identified as cognate inhibitor of matriptase, a membrane-bound serine protease. Paradoxically HAI-1 is also required for matriptase activation, a process that requires sphingosine 1-phosphate (S1P)-mediated translocation of the protease to cell-cell junctions in human mammary epithelial cells. in the current report, we further explored how HAI-1 regulates this protease. First we observed that following SIP treatment HAI-1 was co-translocated with matriptase to cell-cell junctions and that the ... |
|
| Linking Sister Chromatid Cohesion to Apoptosis and Aneuploidy in the Development of Breast Cancer |
01 JUL 2005 |
37 pages |
| Authors:
Debananda Pati; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| The purpose of this project is to identify effector molecules that act as a link between cell proliferation, cell survival, and chromosome stability. The authors have hypothesized that chromosomal segregation and apoptotic pathways are linked and have a role in breast cancer. Rad21 is one of the major cohesin subunits that holds sister chromatids together until anaphase, when proteolytic cleavage by separase allows chromosomal separation. This study demonstrates that in ... |
|
| Linking Sister Chromatid Cohesion to Apoptosis and Aneuploidy in the Development of Breast Cancer |
01 JUL 2005 |
28 pages |
| Authors:
Debananda Pati; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| The purpose of this project is to identify effector molecules that act as a link between cell proliferation, cell survival, and chromosome stability. The authors have hypothesized that chromosomal segregation and apoptotic pathways are linked and have a role in breast cancer. Rad21 is one of the major cohesin subunits that holds sister chromatids together until anaphase, when proteolytic cleavage by separase allows chromosomal separation. This study demonstrates that in ... |
|
| Structural Studies on Toxins and Virulence Factors of Yersinia Pestis |
01 JUL 2005 |
12 pages |
| Authors:
Subramanyam Swaminathan; BROOKHAVEN NATIONAL LAB UPTON NY
|
| In this second annual report, we present our progress on two different areas, protein production and crystallization. We are working on expression and purification of Yop proteins and their complexes. We have made progress in purifying YopB; SycD complex. We are also purifying Yop B, D and E complex to understand the translocation machinery. |
|
| Smad Acetylation: A New Level of Regulation in TGF-Beta Signaling |
JUL 2005 |
11 pages |
| Authors:
Andrea W. Tu; CALIFORNIA UNIV BERKELEY
|
| The transforming growth factor BETA (TGF-BETA) signaling pathway is an essential pathway that results in cell growth arrest when initiated in most epithelial cells. Initiation of TGF-BETA receptors leads to the phosphorylation and translocation of the Smad proteins, the major TGF-BETA intracellular signaling molecule, to the nucleus where transcription of TGF-BETA target genes occur. Aberrations in the Smad proteins are present in many breast cancers indicating their importance. Understanding how ... |
|
| BARC: A Novel Apoptosis Regulator |
JUN 2005 |
65 pages |
| Authors:
Can Jin; John C. Reed; Hong Zhang; Han J. Chae; BURNHAM INST LA JOLLA CA
|
| Breast cancers arise due to an imbalance in cell production relative to cell turnover, resulting in a net accumulation of abnormal cells. Cell turnover is normally achieved in the body by a process known as apoptosis. Defects in apoptosis mechanisms commonly occur in breast cancers and other types of malignancies, making tumor cells difficult to kill by chemotherapy, hormonal therapy, and radiation. Restoring function of cell death pathways is a ... |
|
| Met nuclear Localization and Signaling in Breast Cancer |
MAY 2005 |
14 pages |
| Authors:
Sharon A. Pozner-Moulis; YALE UNIV NEW HAVEN CT SCHOOL OF MEDICINE
|
| Hepatocyte Growth Factor/Met signaling is associated with tumor aggression and poor prognosis in many cancers, including lymph node negative breast carcinomas. High HOP levels have been correlated with worse patient outcome and over-expression of the cytoplasmic region of Met is associated with poor prognosis in lymph node negative breast carcinomas. Immunohistologic assay, using antibodies to the cytoplasmic domain of Met, show Met in the nucleus in cell lines and in ... |
|
| Protein Receptor(s) of Botulinum Neurotoxin |
JAN 2005 |
361 pages |
| Authors:
Bal R. Singh; MASSACHUSETTS UNIV NORTH DARTMOUTH
|
| Seven serotypes of botulinum neurotoxin (BoNT) are a group of water-soluble large proteins that act on the presynaptic nerve cells of the neuro-muscular junctions. BoNTs act intracellulary to block acetylcholine neurotransmitter release leading to the flaccid muscle paralysis in the dreaded botulism disease. In order to enter the neuronal cells, BoNTs bind to as yet to be clearly identified protein receptor(s), which could be targeted to develop proper antidotes. The ... |
|
| 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 ... |
|
| Combinatorial Strategies and High Throughput Screening in Drug Discovery Targeted to Channel of Botulinum |
SEP 2004 |
17 pages |
| Authors:
Mauricio Montel; CALIFORNIA UNIV SAN DIEGO LA JOLLA
|
| This program examines innovative approaches and powerful new technologies to identify selective and potent agents directed to prevent or relieve the neuroparalytic toxic actions of botulinum toxin A (BoNTA)1. The focus is on the ion channel forming activity pf BoNTs as a validated target to screen for inhibitors of the translocation of the light chain into the cytosol and therefore to attenuate the BoNT neurotoxicity. The key of the program ... |
|
| Linking Sister Chromatid Cohesion to Apoptosis and Aneuploidy in the Development of Breast Cancer |
JUL 2004 |
28 pages |
| Authors:
Debananda Pati; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| The purpose of this project is to identify effector molecules that act as a link between cell proliferation, cell survival and chromosomes stability. We have hypothesized that chromosomal segregation and apoptotic pathways are linked and have a role in breast cancer. Rad21 is one of the major cohesin subunits that holds sister chromatids together until anaphase, when proteolytic cleavage by separase allows chromosomal separation. Our study demonstrates that in contrast ... |
|
| Matriptase Activation in Breast Cancer Progression |
JUN 2004 |
18 pages |
| Authors:
Chen-Yong Lin; GEORGETOWN UNIV WASHINGTON DC
|
| In the current research plan, we proposed to study the mechanism for activation of matriptase, a membrane-bound serine protease. Previously, we showed matriptase is activated via transactivation, where the interactions among latent matriptase molecules, HAI-1, and other unidentified proteins are required for the proceeding of activational cleavage. in non-transformed mammary epithelial cells, matriptase activation can be Induced by sphingosine 1- phosphate (sip), a blood-borne bioactive phospholipid. in the past one-year, ... |
|
| Synthesis of Targeted Drugs for Treating Breast Cancer |
APR 2004 |
13 pages |
| Authors:
Jerald C. Hinshaw; UTAH UNIV SALT LAKE CITY
|
| New chemotherapeutic agents are needed for the improved treatment of breast cancer. In this proposal, we disclose a new approach to the design of anti-cancer drugs. Our method is to synthesize new drug conjugates that incorporate: (i) a specific breast cancer cell-targeting component; (ii) a rapid cell membrane translocating /nuclear localization moiety and; (iii) the capability to counter multi-drug resistance mediated by P-glycoprotein and related cellular efflux pumps. The conjugates ... |
|
| A Novel Apoptotic Molecule Bok for the Treatment of Breast Cancer |
MAR 2004 |
11 pages |
| Authors:
Geoffrey A. Bartholomeusz; M D ANDERSON CANCER CENTER HOUSTON TX
|
| We have shown by transient expression of hBok that this member of the Bc1-2 pro-apoptotic family is unique since its translocation to the nucleus is important for protein to induced apoptosis. Concern were raised since our observation did not apply to endogenous Bok. We are now in a position to detect endogenous Bok by western Blot analysis and have shown that endogenous Bok is present in the cytoplasm and nucleus ... |
|
| Structural Studies on Intact Clostridium Botulinum Neurotoxins Complexes with Inhibitors Leading to Drug Design |
FEB 2004 |
28 pages |
| Authors:
Subramanyam Swaminathan; BROOKHAVEN NATIONAL LAB UPTON NY
|
| In this second annual report we present our progress on three different areas. We are working on intact BoNT/B to identify small molecules that could be used to block the toxic activity. In this respect, we have discovered that two calcium ions are bound to BoNT/B and that at least one of them plays an important role in the translocation of the catalytic domain into the cytosol. We propose that ... |
|
| Mechanisms of Neuronal Apoptosis In Vivo |
FEB 2004 |
462 pages |
| Authors:
Lee J. Martin; JOHNS HOPKINS UNIV BALTIMORE MD
|
| Neuronal cell death in the central nervous system (CNS) has broad significance for military personnel in combat and veteran status and civilians. Neuronal cell death in the form of apoptosis or necrosis occurs after exposure to neurotoxins, chemical warfare agents, radiation, viruses, and after seizures, trauma, limb amputation, and hypoxic-ischemia caused by cardiac arrest, stroke, asphyxiation, and increased intracranial pressure. Secondary brain damage can result from hemorrhagic and hypovolemic shock. ... |
|
| Role of Nuclear Receptor Coregulators in Hormone Resistant Breast Cancer |
SEP 2003 |
74 pages |
| Authors:
Lisa Nitao; Kathryn B. Horowitz; COLORADO UNIV HEALTH SCIENCES CENTER DENVER
|
| We propose that coregulatory proteins influence the direction of transcription by antagonist-occupied steroid receptors. We screened for such proteins and identified three cDNA fragments encoding peptides that interact with antagonist-bound PRs. The aims were to clone complete cDNAs; define the role of the unknown proteins on receptor activity; and determine the role of the unknown proteins in hormone dependency of breast cancers. Major findings: We have focused on one novel ... |
|
| Molecular Mechanisms of Dopamine Receptor Mediated Neuroprotection |
AUG 2003 |
91 pages |
| Authors:
Stuart C. Sealfon; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| Selective dopamine agonists acting at the D2 receptor (D2R) inhibit the toxicity caused by oxidative stress through a novel growth factor dependent and G protein independent signaling pathway. In response to oxidative stress, PC12 cells activate signaling pathways of both homeostasis, as represented by activation of extracellular regulated kinase (ERK) and pro-apoptotic responses as indicated by p53 activation. Individual cells segregate into two populations within the first hour of stress, ... |
|
| Mechanism of Ras Activation by TGF beta |
JUL 2003 |
88 pages |
| Authors:
Kathleen M. Mulder; PENNSYLVANIA STATE UNIV HERSHEY
|
| Transforming growth factor beta (TGF beta) is a potent growth inhibitor for epithelial cells, often displaying tumor-suppressor activity. As described in our last Progress Report we have identified km23 as a novel TGF beta receptor-interacting protein. Here we show that km23 is ubiquitously expressed in human tissues and that cell-type specific differences in endogenous km23 is TGF beta-dependent. Further, the kinase activity of both TGF beta receptors appears to play ... |
|
| Exploiting and NQ01-Directed, Calpain-Medicated Apoptotic Pathway for Breast Cancer Therapy |
APR 2003 |
92 pages |
| Authors:
Mark W. Wagner; David A. Boothman; CASE WESTERN RESERVE UNIV CLEVELAND OH
|
| The purpose of this proposal was to further understand the molecular mechanisms of beta-lap-induced apoptosis, and its ability to target cancer over normal cells. We believe that beta-lap induces apoptosis through changes in intracellular calcium homeostasis and micron-calpain activation. This will be tested via two specific aims using NQ01-expressing and non-expressing (beta-lap sensitive and resistant, respectively) MDA-MB-468 breast cancer cells as a model system. The first aim was to determine ... |
|
| A System Dynamics Investigation of Genetic Drift and Translocation in the Red-Cockaded Woodpecker Metapopulation |
MAR 2003 |
95 pages |
| Authors:
Jason E. Yates; AIR FORCE INST OF TECH WRIGHT-PATTERSON AFB OH SCHOOL OF ENGINEERING AND MANAGEMENT
|
| The red-cockaded woodpecker (Picoides borealis) is classified under the Endangered Species Act of 1973 as an endangered species As such, the red- cockaded woodpecker (RCW) is afforded strict protection in an effort to return the RCW population to a self-sustainable level. Endemic to southeastern United States mature pine forests, the presence of the RCW impacts the operations of many Department of Defense (DoD) installations. A particular challenge in sustaining what ... |
|
| The Role of KSR-Associated Kinases in Breast Cancer Signaling |
FEB 2003 |
5 pages |
| Authors:
Steven J. Schreiner; Robert E. Lewis; NEBRASKA UNIV MEDICAL CENTER OMAHA
|
| Kinase Suppressor of Ras (KSR) is a putative scaffold of the Raf/MEK/ ERK kinase cascade. This kinase cascade is critical for the proliferation of malignant breast carcinomas. We have examined the effect of phosphorylation and protein-protein interaction on the subcellular distribution and biological activity of KSR. KSR is phosphorylated on at least 15 residues in intact cells. This phosphorylation is due to KSR-associated kinases and not due to autophosphorylation by ... |
|
| Role of Sister Chromatid Cohesion in the Apoptotic Response of Normal and Malignant Mammary Cells with Known Aneuploidy |
SEP 2002 |
34 pages |
| Authors:
Debananda Pati; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| The purpose of the study was to identify the effector molecules that act as a link between cell proliferation, cell survival and chromosomes stability. We have hypothesized that chromosomal segregation and apoptotic pathways are linked and have a role in the development of aneuploidy in breast tumors. Rad21 is one of the major cohesin subunits that holds sister chromatids together until anaphase, when proteolytic cleavage by separase, allows chromosomal separation. ... |
|
| Linking Sister Chromatid Cohesion to Apoptosis and Aneuploidy in the Development of Breast Cancer |
JUL 2002 |
37 pages |
| Authors:
Debananda Pati; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| The purpose of the study is to identify the effector molecules that act as a link between cell proliferation, cell survival and chromosomes stability. We have hypothesized that chromosomal segregation and apoptotic pathways are linked and have a role in the development of aneuploidy in breast tumors. Rad2l is one of the major cohesin subunits that holds sister chromatids together until anaphase, when proteolytic cleavage by separase, allows chromosomal separation. ... |
|
| Pulsed Electric Fields for Biological Weapons Defense |
2002 |
12 pages |
| Authors:
Martin A. Gundersen; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES DEPT OF ELECTRICAL ENGINEERINGAND ELECTROPHYSICS
|
| The project has demonstrated that ultra-short, high-field pulses are a useful tool for study of cellular responses. The research has established that intracellular effects including apoptosis can be induced by the application of short, intense (but low total energy) electric pulses, and has seen variability in cell response. Experiments on human cells have produced convincing evidence that these applied fields nondestructively alter subcellular processes and can be investigated using biophotonic ... |
|
| Neurofibromatosis 2 Tumor Suppressor Protein, Merlin, in Cellular Signaling to Actin Cytoskeleton |
OCT 2000 |
96 pages |
| Authors:
Vijaya Ramesh; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
| Th gene encoding the NF2 tumor suppressor showed a strong similarity to a family of cytoskeleton-associated proteins and was named merlin (for moesin-ezrin-radixin-like protein). The critical question as to how the NF2 gene product, merlin, acts as a tumor suppressor largely remains unanswered because of the limited knowledge of the physiological function of merlin. Our studies reveal that merlin can bind to actin directly and isoform 2 of merlin which ... |
|
| Novel Peptide/Protein Delivery System Targeting erbB2-Overexpressing Breast Cancer Cells |
AUG 2000 |
9 pages |
| Authors:
Dihau Yu; M D ANDERSON CANCER CENTER HOUSTON TX
|
| A major goal of this Idea proposal is to determine whether the penetratin-based peptide delivery system may be developed to effectively deliver anti-cancer therapeutic peptides/proteins into breast cancer cells. We have fulfilled the objective 1 (Tasks 1-3) during the first year of the grant support. Although we experienced initial difficulties labeling the peptides with FITC, we finally were able to succeed in chemical synthesis of FITC-labeled penetratin peptides. When evaluating ... |
|
| Mitochondrial Apoptosis: A New Foundation for Combing Agents in Prostate Cancer Treatment |
MAR 2000 |
88 pages |
| Authors:
Charles E. Myers; VIRGINIA UNIV CHARLOTTESVILLE
|
| Mitochondrial Apoptosis: A New Foundation for Combing Agents in Prostate Cancer Treatment. Charles E. Myers, M.D. This grant sought to examine synergy between androgen withdrawal and drugs known to have activity against hormone-refractory prostate cancer. The hypothesis is that apoptosis induced by these various agents would converge on mitochondria enhancing tumor cell kill. During the first year, we were able to clearly show that none of the agents tested were ... |
|
| Ret Receptor: Functional Consequences of Oncogenic Rearrangements |
OCT 1998 |
44 pages |
| Authors:
Susan S. Taylor; CALIFORNIA UNIV SAN DIEGO LA JOLLA
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| The ret/ptc2 gene was cloned from human papillary thyroid carcinomas, and is the product of a reciprocal chromosomal rearrangement, translocation event between the cAMP dependent protein kinase regulatory subunit I alpha (RI alpha) and the tyrosine kinase domain of the Ret receptor. Ret/ptc2 is a dimer which is autophosphorylated, soluble, and constitutively active. We generated a computer model of the Ret/ptc2 kinase domain, expressed and purified Ret/ptc2, developed a kinase ... |
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| The Role of PKC in Retinoic Acid Regulation of Human Mammary Cancer Cell Proliferation |
SEP 1998 |
35 pages |
| Authors:
Yunhi Cho; David A. Talmage; COLUMBIA UNIV NEW YORK
|
| The data presented in this annual report (for award DAMDI7-96-I-6022) support our hypothesis for a mechanism of retinoic acid -induced growth arrest of human breast cancer cells. Specifically we believe that retinoic acid induced growth arrest of human breast cancer cells requires protein kinase Ca expression. The constitutive expression of PKCa in hormone independent, MDA-MB- 231 cells induced retinoic acid sensitivity to inhibit the uncontrolled proliferation and to alter the ... |
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