| Environmental Medicine Genome Bank (EMGB): Hardy-Weinberg Equilibrium at an Eotaxin Locus on Chromosome 17 |
JAN 2002 |
17 pages |
| Authors:
Murad Dikeidek; Amy Bastille; Larry A. Sonna; Craig M. Lilly; ARMY RESEARCH INST OF ENVIRONMENTAL MEDICINE NATICK MA
|
 | The Environmental Medicine Genome Bank (EMGB) was used to test a low cost, high throughput, polymerase chain reaction (PCR) - based genetic strategy to distinguish 3 genotypes for a single nucleotide polymorphism (SNP) in the eotaxin gene located on chromosome 17. Using amplification refractory mutation system PCR (ARMS-PCR), we determined the eotaxin ALA23-THR23 genotypes of 233 samples in the EMGB. The observed allele frequencies were then used to determine the ... |
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| Digital Filters for Gene Prediction Applications |
2002 |
5 pages |
| Authors:
P. P. Vaidyanathan; Byung-Jun Yoon; CALIFORNIA INST OF TECH PASADENA DEPT OF ELECTRICAL ENGINEERING
|
 | It has been observed by many researchers that the protein-coding regions of DNA sequences exhibit a period-3 behavior due to codon structure. Identification of the period-3 regions helps in predicting the gene locations and in fact allows the prediction of specific exons within the genes of eucaryotic cells. Traditionally these regions are identified with the help of techniques such as the windowed DFT. In this paper we consider the use ... |
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| Membrane Fusion Protein Annexin 7: A Common Site of Action for Calcium, Guanosine Triphosphate, Protein Kinase C and Botulinum Toxin Type C in Regulated Exocytosis |
2002 |
170 pages |
| Authors:
Hung Caohuy; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
|
 | Numerous studies have shown that regulated exocytosis is activated simultaneously by calcium, guanosine triphosphate (GTP) and protein kinase C (PKC), and that this process is specifically inhibited by botulinum toxins (BoNTs). Although phenomenologically well known, the specific sites of action for these agents in the late stage of exocytosis, membrane fusion, remain unknown. In this research project, we combined both in vitro and in vivo approaches to directly test the ... |
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| The Role of DNA Methyltransferase in the Progression of Breast Cancer to a Hormone Independent Phenotype |
DEC 2001 |
90 pages |
| Authors:
Lan Yan; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOLOF MEDICINE
|
 | Approximately a quarter of breast cancer patients lack estrogen receptor (ER) expression and respond poorly to hormonal treatment. Absence of ER expression is associated with lack of transcript, methylation of the CpG island in the promoter region of this gene, and increased DNMT activity. This study addresses the hypothesis that specific inhibition of DNMT1 by antisense oligonucleotides (DNMTl ASO) is sufficient to re-express ER in ER- human breast cancer cell ... |
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| Bioinspired Nanocarriers Designed to Enhance Intracellular Delivery of Biotherapeutics |
25 OCT 2001 |
|
| Authors:
Patrick S. Stayton; A. S. Hoffman; UNIV OF WASHINGTON SEATTLE DEPT OF BIOENGINEERING
|
 | The biotechnology and pharmaceutical industries have developed a wide variety of potential therapeutics based on the molecules of biology: DNA, RNA and proteins. While these therapeutics have tremendous potential, effectively formulating and delivering them has also been a widely recognized challenge. A variety of viruses and toxins have evolved multi-functional biopolymer complexes to solve this problem by directing uptake and enhancing biomolecular transport to the cytoplasm from the low pH ... |
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| Indicator Based and Indicator - Free Electrochemical DNA Biosensors |
25 OCT 2001 |
|
| Authors:
Kagan Kerman; Burcu Meric; Dilsat Ozkan; Pinar Kara; Mehmet Ozsoz; EGE UNIV IZMIR (TURKEY) FACULTY OF PHARMACY
|
 | The utility and advantages of an indicator free and MB based sequence specific DNA hybridization biosensor based on guanine and adenine oxidation signals and MB reduction signals have been demonstrated. Indicator free detection system is simple, cost-effective and provides rapid detection. The application of DPV at CPE fulfilled the expectations for the direct detection of hybridization between the known oligonucleotides. This procedure can be employed to detect specific gene sequences ... |
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| DNA Repair and Checkpoint Genes as NF1 Modifiers |
OCT 2001 |
9 pages |
| Authors:
Andre Bernards; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
 | This study aims to determine whether common protein altering single nucleotide polymorphisms (SNPs) in DNA repair or cell cycle checkpoint genes are associated with higher or lower than average neurofibroma numbers. For this allele association study we are collecting DNAs and RNAs from NFl patients that represent the top and bottom 20% of neurofibroma burden. In the first year of this project we established contacts with 169 interested patients, identified ... |
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| A Developmental Approach to Characterizing the Tissue-Invasion Gene Program in Breast Cancer |
SEP 2001 |
24 pages |
| Authors:
Stephen J. Weiss; MICHIGAN UNIV ANN ARBOR
|
 | The changes in the gene program of neoplastic cells that regulate the expression of an invasive phenotype are largely undefined. Direct comparisons of the gene expression profile displayed in normal and carcinomatous breast tissues have provided insights into the mechanisms underlying tumor progression. However, attempts to identify the gene products differentially expressed during invasion in vivo have been hampered by the fact that only a small percentage of the cells ... |
|
| Rapid Induction of Protective Immunity Against Biothreat Agents Using CPG-Based Oglionucleotides |
SEP 2001 |
|
| Authors:
Dennise M. Klinman; HEALTH AND HUMAN SERVICES BETHESDA MD
|
 | This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory 'CpG motifs' to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents. Additional studies examining the ability of these CpG ODN to act as adjuvants when co-administered with vaccines being developed to prevent infection by biowarfare pathogens are also being pursued. Our results indicate that CpG ODN provide protection in mice ... |
|
| The Use of Aptamers in Breast Cancer Anti-Metastasis Therapy |
SEP 2001 |
32 pages |
| Authors:
Besdicht U. Pauli; CORNELL UNIV ITHACA NY
|
 | The objective of this one-year proposal was to initiate studies directed to identify and generate oligonucleotides (aptamers) that block the adhesion between tumor cell beta 4 integrin and endothelial hCLCA2, an adhesion interaction implicated in pulmonary vascular arrest and metastasis of human breast cancer cells. Phase one of these studies was concerned with the generation of an 'aptamer bait' for SELEX random sequence ssRNA library screening. Baits consisted of wild-type, ... |
|
| MHC Genes and Breast Cancer |
SEP 2001 |
15 pages |
| Authors:
Shiv S. Pillai; MASSACHUSETTS GENERAL HOSPITAL BOSTON
|
 | We wished to ascertain whether the failure to inherit putative protective alleles of HLA class II genes is linked to the development of breast cancer. We molecularly typed HLA DPB1, DQB1, DRB1 and DRB3 alleles in 176 Caucasian women diagnosed with early onset breast cancer, and in 215 ethnically matched controls. HLA DQB*03032 was identified in 7% of controls but in no patients with early onset breast cancer (p = ... |
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| A New Invasion and Metastasis Molecule, Tiam1 and its Interaction with the Cytoskeleton are Involved in Human Breast Cancer Progression |
AUG 2001 |
43 pages |
| Authors:
Lilly Y. W. Bourguignon; MIAMI UNIV FL
|
 | In breast tumor cells (e.g., SP1 cells), the guanine nucleotide exchange factor (GEF, the dbl or DR family), Tiam1 (T lymphoma invasion and metastasis) is detected as a 200 kDa protein. Tiam1 is capable of catalyzing GDP/GTP exchange for Rac1. In particular, the aa393-aa738 sequence of Tiam1, which contains the NH2-terminal pleckstrin homology (PHn), a putative coiled coil region (CC) and an additional adjacent region (Ex) (designated as PHn-CC-Ex domain ... |
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| Expression of the Estrogen-Regulated pS2 Gene in MCF-7 Human Breast Cancer Cells |
AUG 2001 |
77 pages |
| Authors:
Lawrence N. Petz; ILLINOIS UNIV CHAMPAIGN
|
 | To gain a better understanding of how estrogen-responsive genes are regulated we utilized in vivo footprinting and in vitro binding assays to define cis elements and transacting factors involved in conferring estrogen responsiveness to the pS2 and PR genes in MCF-7 breast cancer cells. The consensus pS2 ERE half site was protected in the absence of hormone and both the consensus and imperfect ERE half sites were protected in the ... |
|
| New Gene Based Probes for Imaging Breast Cancer with PET |
AUG 2001 |
30 pages |
| Authors:
Sanjiv S. Gambhir; CALIFORNIA UNIV LOS ANGELES
|
 | We are developing methods to image her-2-neu oncogene over-expression in breast cancer using positron emission tomography (PET). Small oligodeoxynucleotides (ODNs) that are complementary to the Her-2-neu messenger RNA (mRNA) are being investigated as potential imaging probes. Fluorine-1B (2 hour half-life positron emitter) has been used to label 15 - 18 mer ODN probes. The labeling of an ODN to Fluorine-18 has been particularly troublesome because of the limited half-life and ... |
|
| Genetic and Epigenetic Mechanisms Underlying Acute and Delayed Neurodegenerative Consequences of Stress and Anticholinesterase Exposure |
AUG 2001 |
296 pages |
| Authors:
Hermona Soreq; HEBREW UNIV JERUSALEM (ISRAEL)
|
 | We have observed the role of the stress-associated acetylcholinesterase variant, AChE-R in several model systems. In AChE transgenic mice, the neuronal overexpression of AChE-R is associated with behavioral impairments. In another animal model, the honey bee, developmental reduction of ache gene expression paralleled their normal, consistent improvement of behavioral functions, and experimental improvement under mild rivastigmine exposure. |
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| The Involvement of Human Cyr61 in Heregulin Induction of Breast Tumor Progression |
AUG 2001 |
39 pages |
| Authors:
Miaw-Sheue Tsai; CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB
|
 | Cyr61, a member of the CCN gene family, was isolated and identified by differential expression between estrogen receptor (ER)-positive and ER- negative breast cancer cells. Cyr61 is a ligand for the integrin av-beta-3, which is involved in tumorigenesis and angiogenesis (formation of new blood vessels). We showed previously that expression of Cyr61 in HRG-transfected MCF-7 cells is greatly increased compared to parental MCF-7 cells. We also showed that Cyr61 is ... |
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| The Identification of Genes Differentially Regulated by Progestins and Glucorticoids in Human Breast Cancer Cells |
JUL 2001 |
11 pages |
| Authors:
Yihong Wan; Steven K. Nordeen; COLORADO UNIV HEALTH SCIENCES CENTER DENVER
|
 | Progestins and glucocorticoids are two classes of steroid hormone with very distinct biological functions. Progestins have been shown to relate to the incidence and progression of breast cancer, but glucocorticoids have no direct relation with breast cancer to our knowledge. However, progesterone receptor and glucocorticoid receptor share many structural and functional similarities including identical DNA sequence recognition characteristics. To understand the role of progestins in breast cancer and how progesterone ... |
|
| EGF-Receptor Signaling in Endocytosis Deficient Cells |
JUL 2001 |
24 pages |
| Authors:
Brian Ceresa; Sandra L. Schmid; OKLAHOMA UNIV HEALTH SCIENCES CENTER OKLAHOMA CITY
|
 | Award DAMDl7-99-l-9367 seeks to understand the role of membrane trafficking in Epidermal Growth Factor Receptor (EGFR) signal transduction. We have been using a tissue culture model system (HeLa cells) to isolate the activated EGFR at distinct stages in the endocytic pathway. Our research has focused on rab5, a small molecular weight GTPase, implicated in the biogenesis of the early endosome. Mutations to modulate the guanine nucleotide binding properties of this ... |
|
| Microarray Technology to Study the Role of Genetic Polymorphisms in Breast Cancer Risk |
JUL 2001 |
12 pages |
| Authors:
Hilmi Ozcelik; MOUNT SINAI HOSPITAL TORONTO (ONTARIO)
|
 | It has been suggested that low penetrant alleles are associated with breast cancer risk. Although the contribution of low penetrant alleles to the individual risk is relatively small, they can contribute to a large proportion of breast cancer cases in the population. In this study we took the candidate gene approach to study the association of 32 different genetic polymorphisms in a population-based sample. We have also proposed to use ... |
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| Effect of a Single Nucleotide Polymorphism (NP) on Breast Cancer Invasion |
JUL 2001 |
13 pages |
| Authors:
Colby A. Wyatt; Constance E. Brinckerhoff; DARTMOUTH COLL HANOVER NH
|
 | The lethality of breast cancer is derived from its ability to metastasize, and matrix metalloproteinases (MMPs) facilitate cellular invasion by degrading the extracellular matrix. One component of MMP regulation is transcription. We have identified a single nucleotide polymorphism (SNP) that enhances the transcriptional activity of MMP-l promoters in transient transfections. The SNP consists of an extra guanine nucleotide that creates an ETS family transcription factor binding site (2G). We utilized ... |
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| Direct Effects of Folate Metabolism on Gene Expression in Metastatic Breast Cancer |
JUL 2001 |
22 pages |
| Authors:
Monica Calero; Ruth N. Collins; CORNELL UNIV ITHACA NY
|
 | Rab proteins are small CTPases that are essential elements of the protein transport machinery of eukaryotic cells. Each round of membrane transport requires a cycle of Rab protein nucleotide binding and hydrolysis. My research project consists in the study of Rab CTPases,the way in which they regulate intracellular transport, and the elucidation of mechanisms by which proteins involved in intracellular protein trafficking are linked to uncontrolled cellular proliferation and cancer. ... |
|
| DNA Nanotechnology for Massive Information Storage |
JUL 2001 |
22 pages |
| Authors:
Nadrian Seeman; W. Morrison; E. Monteith; D. Gallaro; J. Filsinger; NEW YORK UNIV NY
|
 | Studies conducted under the sponsorship of this award consisted of advances in DNA nanotechnology so that it will ultimately be useful for massive information storage. The highlights of the progress fail into the categories of DNA nanomechanical devices, self-assembled DNA arrays in 1D and 2D, and the development of new DNA motifs, and their use in these systems. We have developed a DNA nanomechanical device predicated on the B-Z structural ... |
|
| Unique G-Rich Oligonucleotides Which Inhibit the Growth of Prostatic Carcinoma Cells |
JUL 2001 |
32 pages |
| Authors:
Donald M. Miller; Paula J. Bates; John O. Trent; LOUISVILLE UNIV KY
|
 | This proposal was based on our original observation that certain G- rich oligonucleotides (GROs) inhibited the growth of cultured prostate cancer cells. The sequences of the active oligonucleotides led us to hypothesize that GROs could form G-quartet containing structures that bind to specific cellular proteins. The overall goal of this proposal was to characterize the structure and mechanism of these novel oligonucleotides. In the first half of this study, the ... |
|
| Induction of Radiosensitization by Antisense Oligonucleotide Gene Therapy |
JUL 2001 |
50 pages |
| Authors:
Meredith McCracken; WEST VIRGINIA UNIV RESEARCH CORP MORGANTOWN*
|
 | Protein kinase C (PKC) promotes cell survival in response to ionizing radiation in a variety of experimental models including human carcinoma, human glioblastoma, and transformed mouse embryo fibroblast cell lines. The purpose of this project is to enhance radiation-induced mammary tumor cell death by inhibition of specific PKC isoforms. Antisense oligonucleotides have been introduced into human breast tumor cell lines to selectively inhibit PKC isoforms. MDA-MB- 231 and MCF-7 cells ... |
|
| Transcription-Coupled Repair and Breast Cancer |
JUN 2001 |
11 pages |
| Authors:
Isabel Mellon; KENTUCKY UNIV RESEARCH FOUNDATION LEXINGTON
|
 | We have studied transcription-coupled repair (TCR) and global genome repair (GGR) of UV damage in the dihydrofolate reductase gene in HCCl937 cells. HCC1937 is a human breast cancer cell line that has mutations in BRCAl. We found no defect in the removal of UV-induced cyclobutane pyrimidine dimers. Hence, we and others find no evidence for a linkage between defects in either BRCAl or BRCA2 and reduced repair of "bulky adducts." ... |
|
| Pain Transmission in Humans: The Role of Novel Sensory Ion Channels |
MAY 2001 |
54 pages |
| Authors:
Stephen R. Ikeda; DONALD GUTHRIE FOUNDATION FOR EDUCATIONAND RESEARCH SAYRE PA
|
 | The primary accomplishments of the previous funding period were: 1) cloning and expression of the mouse isoform of Scn10a gene product (SNS; TTX- resistant sodium channel); 2) functional heterologous expression and initial biophysical characterization of the mouse Scn10a gene product in sympathetic neurons; 3) cloning and sequencing of 4 Kbp of upstream genomic DNA; and 4) identification of BAC (bacterial artificial chromosome) clones harboring the mouse Scn10a gene. The nucleotide ... |
|
| Protection Against the Acute and Delayed Toxicities of Sulfur Mustard |
APR 2001 |
26 pages |
| Authors:
Zdenka Matijasevic; Michael Volkert; MASSACHUSETTS UNIV MEDICAL CENTER WORCESTER
|
 | Both the acute and delayed toxicities of DNA damaging agents like sulfur mustard (SM) appear to represent the outcome of a race between protective and toxic pathways triggered by DNA damage. Results obtained within the framework of our first objective to investigate the mechanisms involved in processing SM-induced DNA modifications, have revealed that both nucleotide excision repair (NER) and base excision repair (BER) are involved in processing SM-induced DNA damage. ... |
|
| Development of Triplex-Forming Oligonucleotides to Inhibit Expression of the c-myc Oncogene in Breast Cancer Cells |
APR 2001 |
7 pages |
| Authors:
Eileen M. McGuffie; Carlo V. Catapano; MEDICAL UNIV OF SOUTH CAROLINA CHARLESTON
|
 | Triple helix-forming oligonucleotides (TFOs) bind with high affinity and specificity to homopurine/homopyrimidine sequences in double-stranded DNA. Oligonucleotide- directed triplex formation in gene promoter regions has been shown to inhibit transcription of targeted genes. C-myc is a growth%-promoting oncogene that is deregulated and overexpressed in breast and other cancers. Our research is designed to assess TFO-mediated reduction of c-myc expression as a means of decreasing breast tumor growth. The purpose of ... |
|
| Elucidating Mechanisms of Bacterial Response |
31 JAN 2001 |
11 pages |
| Authors:
John Cavanagh; NORTH CAROLINA STATE UNIV AT RALEIGH DEPT OF BIOCHEMISTRY
|
 | The overall goal of this project was to determine whether protein flexibility contributed to molecular recognition and binding events for proteins critical in the development of bacterial virulence. Such a correlation would provide for an as yet untapped focal point for anti-infective design. |
|
| Phaseolotoxin Biosynthesis: Molecular Mechanisms of Thermoregulation |
20 JAN 2001 |
18 pages |
| Authors:
Suresh S. Patil; HAWAII UNIV HONOLULU
|
 | The production phaseolotoxin (PT) and PT-resistant ornithine carbamoyl-transferase (encoded by argK of Pseudomonas syringae pv. phaseolicola are thermoregulated; both are produced at 1 18 C, but neither is produced at 30 C. At 30 C (but not at 18 C) the bacterium produces a DNA-binding protein that binds (in vitro) to sites in the upstream region of argK. Our hypothesis is that this protein is a transcription factor (TP) which ... |
|
| DNA Damages Induced Neuronal Death |
OCT 2000 |
27 pages |
| Authors:
Glen Kisby; OREGON UNIV HEALTH SCIENCES CENTER PORTLAND
|
 | Neuronal cultures prepared from the cerebellum, cortex, or midbrain of wild-type, DNA repair-overexpressing (i.e., O(exp 6)-methylguanine methyltransferase, MGMT(+)) or DNA repair-deficient (i.e., XPA(-/-)) mice were examined for sensitivity to nitrogen mustard (HN2) or the related alkylating agent methylazoxymethanol (MAM). The MGMT(+) studies examined whether the neurotoxicity of HN2 and MAM could be blocked by overexpressing MGMT in cerebellar neurons. As proposed, neuronal survival, ... |
|
| Mechanisms of Thyroid Hormone-Induced Osteoporosis |
OCT 2000 |
56 pages |
| Authors:
Paula H. Stern; NORTHWESTERN UNIV EVANSTON IL
|
 | Thyroid hormone (T3) is essential for skeletal growth and development. Excess T3, especially in adults, can cause bone loss and increased fracture susceptibility. Our previous data showed that T3 increases local production of a critical bone growth factor, insulin-like growth factor-I (IGF- I), and potentiates interleukin-1 (IL-I)-stimulated production of the osteoclastogenic cytokine interleukin-6 (IL-6). The current proposal was to determine whether these local factors are important in the effects of ... |
|
| High-Throughput Array Instrument for DNA-Based Breast Cancer Diagnostics |
OCT 2000 |
12 pages |
| Authors:
Harold P. Swerdlow; KAROLINSKA INST STOCKHOLM (SWEDEN)
|
 | The aim of this project is to develop improved methods for the production, processing, and analysis of microarrays (gene-chips) for breast- cancer diagnostics. These methods are based upon large numbers of discrete DNA spots placed on glass microscope slides typically, and hybridized to a probe derived from a tIssue or blood sample. %or breast- cancer diagnostics, there are two likely predominant modes of use. TIssue samples from suspect lesions, e.g., ... |
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| Targeted Therapy of Human Breast Cancer by 2-5A-Antisense Directed Against Telomerase RNA |
SEP 2000 |
15 pages |
| Authors:
John K. Cowell; CLEVELAND CLINIC FOUNDATION OH
|
 | Targeting telomerase RNA (hTR) for degradation by RNAseL in breast cancer cells using antisense molecules linked to 2-5A has demonstrated high levels of cytotoxicity in vivo and in vitro. The antisense molecules used in preliminary studies carried a phosphodiester backbone which can be recognized by endogenous nucleases and so make the half life of these molecules very short. Having demonstrated in vitro that breast cancer cells undergo apoptosis following this ... |
|
| New Gene Based Probes for Imaging Breast Cancer with PET |
AUG 2000 |
16 pages |
| Authors:
Sanjiv Gambhir; CALIFORNIA UNIV LOS ANGELES
|
 | We are developing methods to image her-2-neu oncogene over-expression in breast cancer using positron emission tomography (PET) . Small oligodeoxynucleotides (ODNs) that are complementary to the Her-2-neu messenger RNA (mRNA) are being investigated as potential imaging probes. Fluorine-18 (2 hour half-life positron emitter) has been used to label 15-18 mer ODN probes. The labeling of an ODN to Fluorine-18 has been particularly troublesome because of the limited half-life and the ... |
|
| Parmagnetic Oligonucleotides for Breast Cancer Imaging |
JUL 2000 |
16 pages |
| Authors:
Jennifer Hines; OHIO STATE UNIV RESEARCH FOUNDATION COLUMBUS
|
 | Our hypothesis is that novel paramagnetic oligonucleotide analogs will be useful MR contrast agents for breast cancer imaging. This novel approach of targeting MR contrast agents will ultimately aid in the early detection of metastatic breast cancer. The technical objectives are as follows along with progress to date. 1: Optimization of Paramagnetic Oligonucleotide Chelates: To prepare a series of paramagnetic chelate modified oligonucleotides to assess ... |
|
| The Identification of Genes Differentially Regulated by Progestins and Glucocorticords in Human Breast Cancer Cells |
JUL 2000 |
12 pages |
| Authors:
Yigong Wan; Steven K. Nordeen; COLORADO UNIV HEALTH SCIENCES CENTER DENVER
|
 | Progestins and glucocorticoids are two classes of steroid hormone with very distinct biological functions. Progestins have been shown to be related to the incidence and progression of breast cancer, but glucocorticoids have no direct relation with breast cancer to our knowledge. However, progesterone receptor and glucocorticoid receptor share many structural and functional similarities including identical DNA sequence recognition characteristics. In order to understand ... |
|
| Induction of Radiosensitization by Antisense Oligonucleotide Gene Therapy |
JUL 2000 |
15 pages |
| Authors:
Meredith McCracken; WEST VIRGINIA UNIV MORGANTOWN
|
 | The enzyme, protein kinase C (PKC), is composed of a family of at least 11 isoforms which have distinct functions in signal transduction, tumor progression, and apoptosis. Elevated levels of PKC have been observed in breast cancers. The purpose of this project is to enhance radiation treatment through the use of isoform specific PKC inhibitors. Human breast tumor cell lines were treated with isoform specific AO (antisense oligonucleotides) and radiation. ... |
|
| DNA Methylation Alterations in Breast Cancer |
JUL 2000 |
37 pages |
| Authors:
Fumiichiro Yamamoto; BURNHAM INST LA JOLLA CA
|
 | We proposed to investigate breast cancer-associated DNA methylation alterations using a technique named Methylation Sensitive Restriction Fragment Length Polymorphism (MS-AFLP) which we developed. We performed NotI-MseI MS-AFLP using clinical specimens of normal and tumor breast DNA. We used both combinations of four NotI and four MseI primers with an additional selective residue at the 3' end (4x4 format) and combinations of four NotI with one additional residue and sixteen MseI ... |
|
| Endothelial Cell-Specific Receptor Tie-2 as a Therapeutic Target |
JUL 2000 |
72 pages |
| Authors:
Luyuan Li; GEORGETOWN UNIV WASHINGTON DC
|
 | Angiopoietin-l (Ang-l) has been suggested to function as a promoter of physiological angiogenesis. We have investigated the potential role of Ang-l in breast cancer under clinical conditions and in experimental animals. Ang-l expression in breast cancer specimens was analyzed by using laser capture micro- dissection and RT-PCR. Cancer cells adjacent to micro-vessels expressing Tie-2 were dissected and analyzed. Ang-l mRNA was detected only in 3 of 21 cases and none ... |
|
| Training in Support of a Research Project Entitled "Study an ER Variant Identified from Breast Hyperplasis" |
JUL 2000 |
51 pages |
| Authors:
Linda DEGraffenried; TEXAS UNIV HEALTH SCIENCE CENTER AT SANANTONIO
|
 | Studies have shown that elevated expression levels of estrogen receptor a (ER alpha) in benign breast epithelium is a risk factor for progression to invasive breast cancer, and that breast tumor tissue expresses elevated levels of ER alpha as compared to adjacent normal tissue. Previous studies suggest that ER expression is partly regulated at the transcriptional level. The research funded by this grant has focused on investigating the factors that ... |
|
| Structure of the Estrogen Receptor Dimerization Domain Bound to an Antiestrogenic Phosphotyrosyl Peptide |
JUL 2000 |
21 pages |
| Authors:
Ping Yi; ROCHESTER UNIV NY
|
 | Estrogens are one of the major agents responsible for the development of breast cancer disease. The effects of estrogens are mediated by estrogen receptor (ER) alpha and beta. The ER interacts with specific DNA sequences (EREs) of estrogen responsive genes and modulates gene transcription. The biochemical and physiological features of the newly discovered ER beta remains largely unknown. Estrogen responsive genes contain various imperfect EREs that deviate by one or ... |
|
| Research and Development of Biochip Technologies in Taiwan |
JUL 2000 |
11 pages |
| Authors:
S. J. Ting; A. Chiou; TUNGHAI UNIV TAICHUNG (TAIWAN) DEPT OFPHYSICS
|
 | Recent advancements in several genome-sequencing projects have stimulated an enormous interest in microarray DNA chip technology, especially in biomedical sciences and pharmaceutical industries. The DNA chips facilitated the miniaturization of conventional nucleic acid hybridizations, by either robotically spotting thousands of library cDNAs or in situ synthesis of high-density oligonucleotides onto solid supports. These innovations have found a wide range of applications in molecular biology, especially in studying gene expression and ... |
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| The Failure of Repair Enzymes in the Catechol Estrogen-Induced DNA Damage as Potential Initiating Event in Human Breast Cancer |
JUN 2000 |
28 pages |
| Authors:
Kimberly Chapman; Eleanor G. Rogan; NEBRASKA UNIV MEDICAL CENTER OMAHA
|
 | These studies examine the role estrogens play in the initiating events in cancer. We hypothesize that to develop cancer, one first must have DNA damage, which escapes normal repair and is set as a mutation in a critical gene. DNA damage can occur by direct damage to DNA by estrogen metabolites, as assayed in small oligonucleotides using MALDI-TOF mass spectrometry. Moreover, culturing cells in high, physiological levels of estradiol (E2, ... |
|
| Photo-Electronic Optical Memory - Write/Read System |
APR 2000 |
31 pages |
| Authors:
Michael Heller; NANOGEN INC SAN DIEGO CA
|
 | Chromophoric DNA polymers are being developed for high density optical data storage applications. This project involves the design and synthesis of chromophoric DNA polymers which absorb light energy at a single wavelength and re-emit at predetermined multiple wavelengths. By emitting spectra rather than binary on/off bits, the data word size can be increased significantly and parallel access is enabled. The diffraction limit normally experienced ... |
|
| Relationship Between Pak-Mediated Cell Death and Stress-Activated Kinase Signaling in Breast Cancer |
FEB 2000 |
26 pages |
| Authors:
Frank T. Zenke; SCRIPPS RESEARCH INST LA JOLLA CA
|
 | P2L -ACTIVATED KINASES OR Pak's have been implicated in apoptosis as an upstream regulator with enhancing or suppressing influence and recognized as part of the cell death execution machinery. Here we show that a correlation exists in breast cancer cells between caspase- dependent cleavage of the Pak2 and activation of c-jun kinase. The mode of Pak kinase regulation has recently been identified. Small GTPases like Rac and Cdc42 or sphingoid-like ... |
|
| Identification of Novel Prognostic Genetic Markers in Prostate Cancer |
FEB 2000 |
108 pages |
| Authors:
Jeremy A. Squire; ONTARIO CENTRE FOR REMOTE SENSING TORONTO
|
 | Our progress on prostate cancer (PCa) to date has centered on the application of spectral karyotyping (SKY) and comparative genomic hybridization (CGH) to study consistent chromosomal changes. This work has resulted in three manuscripts (Appendices 1-3). We are now focusing on different cellular mechanisms that could lead to chromosomal aberration and consequent alterations of gene expression. To study early changes in the tumorigenic process, we have analyzed high-grade prostrate intraepithelial ... |
|
| Children's Hospital of Pittsburgh Histocompatibility Center Nucleotide Sequencing for Detection of Alleles at HLA Class I and Class II Loci on Ethnic Minorities |
16 DEC 1999 |
7 pages |
| Authors:
Massimo Trucco; CHILDREN'S HOSPITAL OF PITTSBURGH PA
|
 | The activities of the Children's Hospital of Pittsburgh Histocompatibility Center can be classified under three major categories: 1) the repository service; 2) the molecular typing service; and 3) the research activities aimed at improving the technical support on which the previous two services are working. This year in the Repository, where blood samples from volunteers as bone marrow donors are collected from more than 125 ... |
|
| Theoretical Analysis of DNA Low-Frequency Phonon Modes |
24 SEP 1999 |
8 pages |
| Authors:
Maria Bykhovskaia; VIRGINIA UNIV CHARLOTTESVILLE
|
 | Low frequency phonon modes of a helical DNA olygomers- were calculated and compared. The customized program -cages JiMA and UGAND (developed in Dr. Laverys group lBPc. Paris) were was adopted for IBM PC and employed to minimize potential energy and to calculate vibrational frequencies of a molecule. The initial geometry for the B-helix oligonucleotides d(TATATATATATA) d(ATATATATATA) and d(A AAAAAAAAAAA)d(TTTTTTTTTTTT) was created by program JUMNA. The energy ... |
|
| Rapid Induction of Protective Immunity Against Biothreat Agens Using CPG-Based Oglionucleotides |
SEP 1999 |
|
| Authors:
Dennis M. Klinman; DEPARTMENT OF HEALTH AND HUMAN SERVICESWASHINGTON DC
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 | This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory 'CpG' motifs to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents. Our studies indicate that synthetic ODN expressing CpG motifs protect mice from a variety of bacterial and viral pathogens, including Ebola, L. monocytogenes and F. tularensis. ODN-treated animals had stronger Ig and cytokine responses than did controls during the ... |
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