| Regulation of PCNA Function by Tyrosine Phosphorylation in Prostate Cancer |
Oct 2012 |
29 pages |
| Authors:
Shao-Chun Wang; CINCINNATI UNIV OH
|
 | The proliferating cell nuclear antigen (PCNA) has been widely used as a molecular marker for tumor progression and patient prognosis in a variety of human cancers. The PCNA protein has two forms: a non-functional chromatin-unbound form, and a functional chromatin-associated form. The latter form is associated with cancer and tumor progression. Currently, there are no assays which can distinguish these two, distinct forms of the PCNA protein. As a result ... |
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| HER4 Cyt1 and Cyt2 Isoforms Regulate Transcription through Differential Interaction with a Transcriptional Regulator, Yap |
Oct 2012 |
40 pages |
| Authors:
Anna M Misior; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| Our laboratory has previously shown that two isoforms of Epidermal Growth Factor Receptor family member, HER4: Cyt1 and Cyt2 exhibit opposing effects on mammary epithelial cells in vitro and in vivo. In our hands, Cyt1 attenuated growth and promoted differentiation, while Cyt2 promoted cell proliferation of mammary epithelial cells. The two isoforms differ by presence of additional 16 amino acids in Cyt1, which introduces a phosphoinositide- 3 kinase- and third ... |
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| Neuroimmune Interactions, Low-Dose Sarin Inhalation, and Gulf War Syndrome |
Oct 2012 |
123 pages |
| Authors:
Mohan Sopori; LOVELACE BIOMEDICAL AND ENVIRONMENTAL RESEARCH INST ALBUQUERQUE NM
|
| After the Gulf War, many returning soldiers developed an unexplained set of symptoms termed the Gulf War Syndrome (GWS). The symptoms included neurological and respiratory problems. Many veterans were exposed repeatedly to organophosphates/carbamates, including pyridostigmine bromide (neostigmine bromide), organophosphate pesticides, and low-doses of nerve gas that inhibit acetylcholine esterase activity causing a surge in acetylcholine levels and possibly a cholinergic shock. Chronic lowdose exposure to cholinergic agents, such as the ... |
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| A Drug Discovery Partnership for Personalized Breast Cancer Therapy |
Sep 2012 |
24 pages |
| Authors:
Maryam Foroozesh; XAVIER UNIV OF LOUISIANA NEW ORLEANS
|
| Xavier University of Louisiana is in the unique position of developing capability in drug discovery especially in the areas of cancer and health disparities. A significant proportion of the funded research on Xavier s campus including collaborative projects involving Tulane University are related to cancer, drug design, synthesis, and drug delivery. This project expands the partnership between Xavier University and Tulane Cancer Center to develop and validate drugs for breast ... |
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| Probing HER2-PUMA and EGFR-PUMA Crosstalks in Aggressive Breast Cancer |
Sep 2012 |
10 pages |
| Authors:
Hui-Wen Lo; DUKE UNIV DURHAM NC
|
| EGFR and HER2 are overexpressed in 20% and 30% of invasive breast cancer, respectively, and are associated with aggressive tumor subtypes and shortened patient survival. Both receptors are important targets of breast cancer therapy. However, despite the apparent promise of some of these therapies, EGFR- and HER2-based monotherapy and combination regimens have serious limitations and need improvement. The goal of this study is, thus, to gain insights into the biology ... |
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| Targeting Pediatric Glioma with Apoptosis and Autophagy Manipulation |
Aug 2012 |
9 pages |
| Authors:
Amy Keating; COLORADO UNIV AURORA CO
|
| Gliomas are the most common and most deadly solid tumors that affect children. Treatment options are limited and cure rates are dismal. My laboratory has established that Mer and Axl receptor tyrosine kinase are aberrantly overexpressed in gliomas, and that inhibition of these RTKs leads to increased glioma cell apoptosis, decreased tumor cell survival and profoundly improved chemosensitivity. However, I have also recognized that Mer and Axl inhibition is associated ... |
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| The Use of Drugs to Reduce Hearing Loss Following Acute Acoustic Trama |
Jul 2012 |
63 pages |
| Authors:
Roger Hamernik; STATE UNIV OF NEW YORK COLL AT PLATTSBURGH
|
| Following a 108 dB SPL, 4 kHz noise exposure for 6 hours, animals were treated in a rescue paradim with N-Acetyl l-cysteine, Ebselen, D-Methionine, Acetyl L-Carnitine or the Src protein tyrosine kinase inhibitor, KX1-004 and compared to untreated control subjects. Hearing loss, distortion product emissions and cochlear histology data were obtained in each animal. Statistical analyses indicated that there were no significant differences between the control and treated groups. The ... |
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| Fatty Acid Synthase Activity as a Target for c-Met Driven Prostate Cancer |
Jul 2012 |
8 pages |
| Authors:
David T Coleman; LOUISIANA STATE UNIV IN SHREVEPORT HEALTH SCIENCE CENTER
|
| Prostate cancer (PCa) is the most common noncutaneous neoplasia diagnosed in men and represents roughly 10% of cancer-associated mortalities. The lethal phenotype of PCa is primarily characterized by progression of tumor cells to castration-resistance and metastasis. Organ-confined PCa is curable with surgery and/or radiation therapy, however, as the disease becomes metastatic, the likelihood of survival becomes minimal. Key influences in the progression to metastasis are growth factor receptors including the ... |
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| Tyrosine Phosphorylation of Botulinum Neurotoxin Protease Domains |
Jun 2012 |
13 pages |
| Authors:
Stephen Toth; Ernst E Brueggmann; George A Oyler; Leonard A Smith; Harry B Hines; S A Ahmed; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Botulinum neurotoxins are most potent of all toxins. Their N-terminal light chain domain (Lc) translocates into peripheral cholinergic neurons to exert its endoproteolytic action leading to muscle paralysis. Therapeutic development against these toxins is a major challenge due to their in vitro and in vivo structural differences. Although three-dimensional structures and reaction mechanisms are very similar, the seven serotypes designated A through G vastly vary in their intracellular catalytic stability. ... |
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| Intraosseous Hydroxocobalamin in the Treatment of Acute, Severe Cyanide Induced Cardiotoxicity in a Swine (Sus Scrofa) Model - An Alternate Administration Route for Chemical Mass Casualties |
05 Apr 2012 |
7 pages |
| Authors:
Vikhyat Bebarta; Julio Lairet; Rebecca Pitotti; Susan Boudreau; Toni Vargas; Patricia Dixon; Tylan Muncy; AIR FORCE MEDICAL WING (59TH) WILFORD HALL MEDICAL CENTER LACKLAND AFB TX
|
| To compare the rerum to baseline of mean arterial blood pressure (MAP) between 2 groups of swine in acute cyanide toxicity and treated with IV HOC or 10 HOC. We also compared blood cyanide, lactate, pH, nitrotyrosine levels, cerebral oxygenation, and inflammatory markers. 24 swine (48-52kg) were intubated, anesthetized, and instrumented (MAP and cardiac output (CO) monitoring). Cyanide was continuously infused until severe hypotension (50 per cent of baseline MAP). ... |
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| Identification of Androgen Receptor-Regulated Genes in Castration-Recurrent Prostate Cancer |
Apr 2012 |
7 pages |
| Authors:
Irwin H Gelman; HEALTH RESEARCH INC BUFFALO NY
|
| Recent data indicate that castration-recurrent prostate cancer (CR-CaP) progression is driven by the activation of wild-type androgen receptor (AR) through at least two mechanisms: tyrosine phosphorylation by Src family (SFK) and Ack1 tyrosine kinases, and the induction of AR coregulators that regulate the transcriptional activity of AR. It is likely that identifying novel AR-regulated genes in CR-CaP, especially those involving promoters with novel target sequences, will help elucidate the molecular ... |
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| Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer |
Mar 2012 |
19 pages |
| Authors:
Shalini Jain; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Over the last 50 years, the number of cancer related deaths has decreased by only 2%. To achieve reduced breast cancer mortality, it is critical to develop early detection and intervention of breast cancer development at early stages of cancer initiation. This requires better understanding of the critical molecular alterations driving early lesions (atypia) to progress to cancer and developing new interventions based on the observed alterations. Although tamoxifen (Tam) ... |
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| Interrogating Spatio-Mechanical EphA2 Signaling in Cancer |
Mar 2012 |
46 pages |
| Authors:
Jay Groves; CALIFORNIA UNIV BERKELEY
|
| EphA2 is a receptor tyrosine kinase (RTK) overexpressed in many breast cancers. We have found that upon binding to its native ligand, ephrinA1, EphA2 is reorganized into large-scale clusters. Disrupting this clustering alters downstream signaling events, suggesting that this is a mechanosensitive pathway. Now, our goal is to elucidate how the mechanical properties of a cell and its environment play a role in the EphA2 regulatory system and how this ... |
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| HER4 Cyt1 and Cyt2 Isoforms Regulate Transcription Through Differential Interactions with a Transcriptional Regulator, Yap |
Oct 2011 |
28 pages |
| Authors:
Anna M Misior; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| Our laboratory has previously shown that two isoforms of Epidermal Growth Factor Receptor family member, HER4: Cyt1 and Cyt2 exhibit opposing effects on mammary epithelial cells in vitro and in vivo. In our hands, Cyt1 attenuated growth and promoted differentiation, while Cyt2 promoted cell proliferation of mammary epithelial cells. The two isoforms differ by presence of additional 16 amino acids in Cyt1, which introduces a phosphoinositide-3 kinase- and third WW-domain ... |
|
| Role of PTP1B in HER2 Signaling in Breast Cancer |
Oct 2011 |
7 pages |
| Authors:
Sayanti Saha; AMERICAN ASSOCIATION FOR CANCER RESEARCH PHILADELPHIA PA
|
| The receptor tyrosine kinase HER2/ ErbB2 is overexpressed in about 25% of all breast cancers, and presents an attractive therapeutic target. However, drug resistance is a significant clinical problem with current ErbB2-targeted therapies. The development of novel therapeutic strategies demands knowledge of ErbB2 receptor cross-talk with other signaling pathways. Recent reports have shown that Protein Tyrosine Phosphatase 1B (PTP1B) plays a positive role in ErbB2-induced breast cancer in vitroand in ... |
|
| Redox Abnormalities as a Vulnerability Phenotype for Autism and Related Alterations in CNS Development |
Oct 2011 |
21 pages |
| Authors:
Mark D Noble; ROCHESTER UNIV NY
|
| The goals of our work are to develop means of identifying cells, and individuals, that present with a more basal oxidized redox state and to identify molecular mechanisms that functionally integrate such an oxidized state with observations that the multiple environmental insults suggested to be involved in autism pathogenesis also occur in many children that do not develop ASD. This suggests there is an underlying vulnerability phenotype that makes some ... |
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| EphB4 Receptor Tyrosine Kinase in Prostate Cancer |
Sep 2011 |
27 pages |
| Authors:
Nai-ying Yang; SANFORD-BURNHAM MEDICAL RESEARCH INST LA JOLLA CA
|
| EphB4 is a member of the Eph family of receptor tyrosine kinases that is widely expressed in many cancer cell types. High expression of EphB4 has been positively correlated with prostate cancer malignancy. On the other hand, EphB4 has also been shown to be downregulated in other types of cancer. It is unclear how this receptor may promote or suppress oncogenesis under different circumstances. One possibility would be the Eph ... |
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| Overcoming Resistance to Trastuzumab in HER2-Amplified Breast Cancers |
Aug 2011 |
16 pages |
| Authors:
Susan Moody; DANA-FARBER CANCER INST BOSTON MA
|
| The receptor tyrosin kinase HER2 is amplified and/or overexpressed in 25-30% of all breast cancers. Blockade of HER2 with drugs such as trastuzumab or lapatinib has led to clinical benefit in patients with both metastatic and early-stage HER2-amplified breast cancer. However, resistance and disease progression always occurs in patients with metastatic disease, and many patients with early-stage breast cancer experience recurrences despite adjuvant treatment with one of these agents. To ... |
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| Preclinical Testing of Combination Therapy for Malignant Tumors Arising from Neurofibromas |
Jun 2011 |
13 pages |
| Authors:
Gregory Riggins; JOHNS HOPKINS UNIV BALTIMORE MD
|
| About one half of Malignant Peripheral Nerve Sheath Tumors (MPNSTs) arise in Neurofibromatosis Type 1 patients (NF1). Currently, these tumors present very poor clinical prognosis, and despite efforts to find better chemotherapy, there has been little impact on overall patient survival. The extent of surgical resection is the best prognostic factor for these tumors. Our goal is to identify new combination of receptor tyrosine kinase inhibitors that are effective in ... |
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| Identification and Targeting of Upstream Tyrosine Kinases Mediating PI3 Kinase Activation in PTEN Deficient Prostate Cancer |
Jun 2011 |
35 pages |
| Authors:
Steven P Balk; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| The PI3K pathway is activated by PTEN loss in most prostate cancers (PCa), but the contribution of upstream RTKs that may be targeted therapeutically has not been assessed. Immunoblotting of p85 associated proteins in PTEN deficient LNCaP and C4-2 PCa cells showed a small set of tyrosine phosphorylated proteins, but they were not recognized by an anti-pYxxM motif antibody and were not found in PTEN deficient PC3 PCa cells. LC/MS/MS ... |
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| Role of Nonreceptor Protein Kinase Ack 1 in Prostate Cancer |
MAY 2011 |
40 pages |
| Authors:
Charlene Rivera; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| Previously, we have shown that constitutively active Ack1 (caAck1) directly binds and tyrosine phosphorylates the androgen receptor (AR), resulting in ligand-independent AR activity. Moreover, caAck1 transforms LNCaP cells into androgen independent and highly invasive tumors in nude mice. However, the role of Ack1 in prostate cancer initiation and progression within the context of a complex organ remains poorly understood. To address this question, we generated transgenic mice expressing the caAck1 ... |
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| Targeting PCNA Phosphorylation in Breast Cancer |
Apr 2011 |
16 pages |
| Authors:
Vincent J Davisson; Anthony Pedley; Qingshou Chen; Matthew Bartolowits; PURDUE UNIV LAFAYETTE IN
|
| PCNA, an essential protein in the DNA synthesome, was shown to be phosphorylated at Y211 by a nuclear form of EGFR. A consequence of this alteration has been highly correlated with a reduced survival rate of breast cancer patients. However, no basic or clinical studies have addressed if these inhibitors down-regulate the nuclear function of this protein. Inhibitors of EGFR have exciting potential in other cancer diseases but have failed ... |
|
| Role of Melanin in Oncogenesis |
28 FEB 2011 |
13 pages |
| Authors:
Vashisht G. Yennu-Nanda; TEXAS UNIV SMITHVILLE MD ANDERSON CANCER CENTER
|
| Increased solar radiation and other unknown factors induce excess melanin production in melanocytes accumulated in localized areas of the skin, leading to formation of benign moles and infrequently, malignant moles that progress to melanoma. My hypothesis in the current research project is that excess melanin production in melanocytes may cause physico-chemical constraints on the metabolic activities of DNA and RNA, which, in rare instances, may induce pro-survival responses, including mutations, ... |
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| Mechanisms of Twist 1-Induced Invasion in Breast Cancer Metastasis |
JAN 2011 |
47 pages |
| Authors:
Mark Eckert; CALIFORNIA UNIV SAN DIEGO LA JOLLA
|
| Here we identify a novel role for PDGFR-alpha as an essential downstream target of the transcription factor Twist1 for metastasis and local invasion. Twist1 induces the formation of structures called invadopodia that concentrate protease activity to areas of the cell in contact with the extracellular matrix. Twist1-induced invasion and metastasis are dependent on invadopodia formation, as knockdown of an essential invadopodia protein, Tks5, reduces invasion and metastasis. Twist1 induces invadopodia ... |
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| Identification and Targeting of Upstream Tyrosine Kinases Mediating PI3 Kinase Activation in PTEN-Deficient Prostate Cancer |
Jun-2009 |
22 pages |
| Authors:
Steven P Balk; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Class IA PI3K p110 catalytic subunits are activated upon SH2 domain mediated binding of p85 regulatory subunits to tyrosine phosphorylated receptor tyrosine kinases (RTKs) or adaptor proteins. This activation can be enhanced by Ras, and is amplified by PTEN loss in the majority of advanced prostate cancers (PCa). We found that RTK inhibitors lapatinib and sorafenib could suppress PI3K in PTEN deficient PCa cells. However, analysis of p85 associated proteins ... |
|
| A Role for Ubiquitin Binding in Bcr-Abl Transformation |
Jun-2009 |
8 pages |
| Authors:
Ian P Whitehead; UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY NEWARK
|
| We have previously identified a docking site for ubiquitin in the amino-terminus of p210 BCR/ABL. In this proposal we have examined whether this association has implications for BCR/ABL signaling and transforming activity. Our approach was to map the binding site for ubiquitin in BCR/ABL and generate a binding mutant. The binding site is immediately adjacent to the GRB2 binding site, but the two binding activities are genetically separable. Although ubiquitin ... |
|
| Pharmacological and Behavioral Enhancement of Neuroplasticity in the MPTP-Lesioned Mouse and Nonhuman Primate |
May-2009 |
180 pages |
| Authors:
Giselle Petzinger; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| The purpose of this proposal is to investigate the mechanisms involving pharmacological and behavioral enhanced neuroplasticity of the injured basal ganglia. Our central hypothesis is that exercise and pharmacological intervention, specifically the administration of a D2 dopamine-receptor agonist, enhances neuroplasticity by modulating glutamatedopamine interactions. This proposal has two components. Using the MPTP C57BL/6 mouse Component One will test the hypothesis that exercise enhances plasticity of the MPTP-injured basal ganglia through ... |
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| Inhibition of the Protein Tyrosine Phosphatase, SHP-1, in Dendritic Cells to Enhance their Efficacy as Cell-Based Prostate Cancer Vaccines |
May-2009 |
18 pages |
| Authors:
Jonathan M Levitt; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Early preclinical and clinical trials suggest that dendritic cell (DC)-based tumor vaccines are both feasible and safe. However, to date clinical trials of DC-based vaccines have demonstrated only limited efficacy in causing tumorregression despite eliciting measurable systemic T cell responses against prostate cancer. In an effort to enhance the effectiveness of DC-based vaccines against prostate cancer, we have tested the hypothesis that the Src homology region 2 domain-containing phosphatase-1 (SHP-1), ... |
|
| Effect of MUC1 Expression on EGFR Endocytosis and Degradation in Human Breast Cancer Cell Lines |
Apr-2009 |
6 pages |
| Authors:
El; Rachid M Bejjani; ARIZONA UNIV TUCSON
|
| In previous years of this project (2006-2008); we have identified a novel mechanism of internalization and trafficking for the epidermal growth factor receptor in breast cancer cells that overexpress the MUC1 oncoprotein (El Bejjani et al 2006). Additionally, I showed that in the presence of MUC1, EGFR is trafficked to the endocytic recycling compartment and not to the late endosome. This provides an explanation for the decrease in EGFR degradation ... |
|
| Phospholipase C gamma 1: Mechanisms of Adhesion and Role in Migration and Metastasis |
Mar-2009 |
39 pages |
| Authors:
Cornelia Crooke; VANDERBILT UNIV NASHVILLE TN
|
| Phospholipase C-gamma1 (PLC-gamma1) mediates cell adhesion and migration through an undefined mechanism. Here, we examine the role of PLC-gamma1 in cell-matrix adhesion in a hanging drop assay of cell aggregation. Plcg1 Null (-/-) mouse embryonic fibroblasts formed aggregates that were larger and significantly more resistant to dissociation than cells in which PLC-gamma1 is re-expressed (Null + cells). Aggregate formation could be disrupted by inhibition of fibronectin interaction with integrins, indicating ... |
|
| The Role of Backup NHEJ Repair in Creating Genomic Instability in CML. Addendum |
Mar-2009 |
18 pages |
| Authors:
Feyruz Rassool; MARYLAND UNIV BALTIMORE SCHOOL OF MEDICINE
|
| The BCR-ABL1 fusion gene in Philadelphia (Ph)-+ve chronic myeloid leukemis (CML) encodes a constitutively active tyrosine kinase that causes uncontrolled cellular proliferation. BCR-ABL1 expression results in elevated levels of reactive oxygen species (ROS), an increased incidence of DNA double strand breaks (DSBs), error-prone repair and genomic instability. We recently demonstrated that an error-prone alternative (alt) NHEJ pathway involving DNA ligase IIIa/XRCC1 is upregulated in CML cells. Knockdown of alt NHEJ ... |
|
| The Function of PTP1B in Neuroendocrine Differentation of Prostate Cancer |
Jan-2009 |
37 pages |
| Authors:
Jiaoti Huang; ROCHESTER UNIV NY
|
| The goal of the project is to identify the molecular mechanisms responsible for therapeutic failure in prostate cancer patients receiving hormonal therapy Scope: The scope of the project is to use prostate cancer cell lines in in-vitro cell culture systems to study the complex signal transduction pathways that may be responsible for the neuroendocrine differentiation of prostate cancer cells, particularly the relationship of PTP1B to IL-8 signaling through its receptors ... |
|
| ErbB2 Trafficking and Signaling in Human Vestibular Schwannomas |
Oct-2008 |
32 pages |
| Authors:
Marlan R Hansen; J J Clark; Wie Y Yue; Prabhat C Goswami; Bruce J Gantz; IOWA UNIV IOWA CITY
|
| We find that the ErbB2 receptor tyrosine kinase is active in vestibular schwannoma (VS) cells and drives proliferation. Our overall hypothesis is that defects in merlin lead to constitutive ErbB2 activation at the cell membrane and that inhibition of ErbB2 will reduce the survival of VS cells and potentiate the effects of radiation on VSs. In this report we show that VS cells, which lack functional merlin, constitutively express activated ... |
|
| Characterization of NF1 Protein Ubiquitination |
01-Jun-2008 |
8 pages |
| Authors:
Koko Murakami; Victor A Fried; NEW YORK MEDICAL COLL VALHALLA
|
| This project aimed at characterization of NF1 protein ubiquitination system by identifying ubiquitination sites and ligases for neurofibromin. We established the method for obtaining ubiquitinated neurofibromin for mass-spectrometric sequencing and identification of ubiquitination sites of neurofibromin. We confirmed neurofibromin ubiquitination and degradation after mitogenic stimulation by serum and LPA. Cbl-Ring finger ubiquitin ligase mediates ubiquitination and degradation of a variety of signaling proteins in the tyrosine kinase receptor signaling pathway. ... |
|
| Inhibition of the Protein Tyrosine Phosphatase, SHP-1, in Dendritic Cells to Enhance their Efficacy as Cell-Based Prostate Cancer Vaccines |
01-May-2008 |
15 pages |
| Authors:
Jonathan M Levitt; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Early preclinical and clinical trials suggest that dendritic cell (DC)-based tumor vaccines are both feasible and safe. However, to date clinical trials of DC-based vaccines have demonstrated only limited efficacy in causing tumor regression despite eliciting measurable systemic T cell responses against prostate cancer. In an effort to enhance the effectiveness of DC-based vaccines against prostate cancer, we have tested the hypothesis that the Src homology region 2 domain-containing phosphatase-1 ... |
|
| Pharmacological and Behavioral Enhancement of Neuroplasticity in the MPTP-Lesioned Mouse and Nonhuman Primate |
01-May-2008 |
142 pages |
| Authors:
Giselle Petzinger; Michael W Jakowec; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| The purpose of this proposal is to investigate the mechanisms involving pharmacological and behavioral enhanced neuroplasticity of the injured basal ganglia. Our central hypothesis is that exercise and pharmacological intervention, specifically the administration of a D2 dopamine-receptor agonist, enhances neuroplasticity by modulating glutamate-dopamine interactions. This proposal has two components. Using the MPTP C57BL/6 mouse Component One will test the hypothesis that exercise enhances plasticity of the MPTP-injured basal ganglia through ... |
|
| BATTLE: Biomarker-Based Approaches of Targeted Therapy for Lung Cancer Elimination |
01-Apr-2008 |
58 pages |
| Authors:
Waun Ki Hong; Roy Herbst; Li Mao; Edward Kim; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Lung cancer is the leading cause of cancer-related death in both men and women in the United States. Chemotherapy has reached its limit in improving the survival of lung cancer patients. Therefore, a different strategy must be waged in the battle against lung cancer. Targeted therapy, a newly emerged therapeutic approach in lung cancer, has succeeded in some cancer types and demonstrated its initial success in the treatment of lung ... |
|
| The Functional Effect of an Amphiregulin Autocrine Loop on Inflammatory Breast Cancer Progression |
01-Mar-2008 |
36 pages |
| Authors:
Nicole E Willmarth; Stephen P Ethier; WAYNE STATE UNIV DETROIT MI
|
| We have previously shown that an AR/EGFR autocrine loop is required for SUM149 human breast cancer cell proliferation, motility and invasion. In the present studies, we demonstrate that SUM149 cells and human mammary epithelial MCF10A cells that over express AR (MCF10A AR) or are cultured in the presence of exogenous AR, express higher levels of EGFR protein compared with MCF10A cells cultured in EGF. We show that EGFR protein remains ... |
|
| Revealing the Functions of Tenascin-C in 3-D Breast Cancer Models Using Cell Biological and in Silico Approaches |
MAR 2008 |
50 pages |
| Authors:
Agne Tarasevicuite; PENNSYLVANIA UNIV PHILADELPHIA
|
| The extracellular matrix (ECM) glycoprotein tenascin-C (TN-C) is induced in the breast stroma, where it is associated with both breast cancer development and progression, yet its role in this disease remains obscure. To investigate the effects of stromal TN-C on normal human mammary epithelium, we cultured MCF-10A cells in a three-dimensional (3-D) reconstituted basement membrane (Matrigel), either with or without exogenous TN-C. Whereas control cells formed polarized acinar structures, complete ... |
|
| Receptor Tyrosine Kinases as Targets for Treatment of Peripheral Nerve Sheath Tumors in NF 1 Patients |
MAR 2008 |
8 pages |
| Authors:
Victor-Felix Mautner; UNIVERSITY HOSPITAL EPPENDORF HAMBURG (GERMANY)
|
| The purpose of this study is the preclinical testing of multiple available tyrosine kinase inhibitors for NF1-associated benign and malignant tumors in vitro and in vivo. We found frequent copy number changes for EGFR and ERBB2, and also for the tumor suppressor genes PTEN, CDKN2A and TP53 in MPNST. CDKN2A loss was associated with metastasis. EGFR and ERBB2 were frequently expressed in MPNST on the protein level. MPNST and neurofibroma ... |
|
| FGFR4 Downregulation of Cell Adhesion in Prostate Cancer |
Mar-2008 |
11 pages |
| Authors:
Daniel J Donoghue; CALIFORNIA UNIV SAN DIEGO LA JOLLA
|
| We have been successful in creating the necessary constructs for generating prostate cancer cells inducible for FGFR4. Despite our best efforts, however, we have not been able to successfully incorporate the pVgRXR regulatory plasmid into prostate cancer cells. We proceeded by transiently transfecting PC3 prostate cancer cells to look at effects on downstream signaling components and found no significant differences in MAPK activity, NCAM expression or STAT1 and STAT5 localization ... |
|
| Phenotype and Function of Bone Marrow Infiltrating Lymphocytes in Chronic Myelogenous Leukemia |
01-Feb-2008 |
31 pages |
| Authors:
Vinod Pullarkat; CITY OF HOPE DUARTE CA
|
| The aims of this project are to determine the phenotype and antileukemic activity of activated bone marrow infiltrating leukemia (MIL) and compare them to activated peripheral blood lymphocytes from patients with chronic myelogenous leukemia (CML) on imatinib or other tyrosine kinase inhibitor therapy. Bone marrow and peripheral blood specimens were obtained from CML patients who had at least a minor cytogenetic response. The phenotype of MILs and peripheral blood lymphocytes ... |
|
| The Role of Membrane-Derived Second Messengers and Bmx/Etk in Response to Radiation Treatment of Prostate Cancer |
JAN 2008 |
13 pages |
| Authors:
Christopher Willey; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| Radiation-induced activation of the Pl3K/Akt signal transduction pathway requires Akt binding to phosphatidyl-inositol phosphates (PIPs) on the cell membrane. The tyrosine kinase, bone marrow X-kinase (Bmx), binds to PIPs in a manner similar to Akt. Since Bmx is known to be involved in cell growth and survival pathways, Bmx could contribute to the radiation response within the vascular endothelium and prostate cancer, which highly express this protein. We therefore are ... |
|
| Neurotoxin Mitigation |
NOV 2007 |
102 pages |
| Authors:
Steven H. Hinrichs; NEBRASKA UNIV MEDICAL CENTER OMAHA
|
| Organophosphorus esters (OP) are highly toxic poisons used as chemical nerve agents and as pesticides. It is generally agreed that the toxicity from high dose OP exposure involves inhibition of acetyl cholinesterase. The role of other proteins in the toxicity of OP is unknown. Our hypothesis is that several proteins become modified after exposure to OP and that the biological actions of OP are not explained by inhibition of acetylcholinesterase ... |
|
| Molecular Genetic Studies of Bone Mechanical Strain and of Pedigrees with Very High Bone Density |
NOV 2007 |
41 pages |
| Authors:
Subburaman Mohan; LOMA LINDA VETERANS ASSOCIATION FOR RESEARCH AND EDUCATION REDLANDS CA
|
| The primary goal of the proposed work on bone mechanical strain focuses on identifying the genes and their functions involved in mediating the anabolic skeletal response to mechanical stress. Two hypotheses have been proposed: I) Quantitative trait loci analysis using the four point bending technique in two strains of mice exhibiting extreme differences in loading response will lead to identification of chromosomal locations of genes involved in variation in skeletal ... |
|
| Tumor Suppressor Activity of the EphB2 Receptor in Prostate Cancer |
NOV 2007 |
15 pages |
| Authors:
Elena B. Pasquale; BURNHAM INST LA JOLLA CA
|
| Mutations have been recently identified in the EphB2 receptor gene in prostate cancer suggesting that EphB2, a member of the large Eph receptor tyrosine kinase family, is a tumor suppressor in prostate cancer. Consistent with a tumor suppressor activity, we found that EphB2 is more highly expressed in non-transformed BPH-1 prostate epithelial cells than in several prostate cancer cell lines. Furthermore, EphB2 expression was rapidly lost in stably transfected DU145 ... |
|
| Mechanisms of Disease Persistence in Chronic Myelogenous Leukemia |
01-Oct-2007 |
18 pages |
| Authors:
Richard L Defoe; Brian J Druker; OREGON UNIV PORTLAND
|
| Disease persistence is the main issue faced by CML patients on therapy with imatinib and eradication of persistent malignant cells will be critical for the long-term success of kinase inhibitor therapy. Mechanisms underlying acquired resistance to imatinib have been extensively studied and the manner by which mutations of the Bcr-Abl kinase domain can reduce or eliminate sensitivity of CML cells to imatinib has been well characterized. Disease persistence in responding ... |
|
| Recombinant Peptides as Biomarkers for Metastatic Breast Cancer Response |
OCT 2007 |
11 pages |
| Authors:
Roberto Diaz; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| The overall objective of this Proposal is to rapidly and non-invasively assess metastatic breast cancer susceptibility to tyrosine kinase inhibitors (TKIs) by use of recombinant peptides that bind within tumors. We will then identify the receptor to which the recombinant peptide binds. We propose that this receptor protein becomes unveiled following therapy. These recombinant peptides in turn can be labeled with internal emitters to provide a means of non-invasive monitoring ... |
|
| The Transgenic TGF-Alpha or EGFR1 Overexpression Mouse Model for Symptom Complex Research |
OCT 2007 |
7 pages |
| Authors:
Tyvin Rich; VIRGINIA UNIV CHARLOTTESVILLE
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| The TGF- transgenic over expression model has been used to study circadian running wheel activity (RWA) in C57Bl6 mice. The genotype of each transgenic animal is determined by PCR analysis of tissue and gel electorphoresis. Male and female transgenic and control animals have been assessed for RWA, phase, and total amount of activity in a light controlled environment using a 12:12 hour light/dark (LD) cycle and in constant darkness (DD). ... |
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| Methods and Applications of Computational Chemistry |
04 JUL 2007 |
107 pages |
| Authors:
JACKSON STATE UNIV MS
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| Conference papers on the subjects of computational chemistry, molecular biology, molecular structure, crystallography, and single crystals (abstracts only). |
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Reports by Keyword(s)
TYROSINE
