| Obstructing Androgen Receptor Activation in Prostate Cancer Cells Through Post-translational Modification by NEDD8 |
May 2011 |
5 pages |
| Authors:
J D Chen; ROBERT WOOD JOHNSON MEDICAL SCHOOL PISCATAWAY NJ
|
 | The overall goal of this study is to investigate the effect of post-translational NEDD8 modification on androgen receptor. In year 3, we proposed to establish Jab1 shRNA expressing lines of prostate cancer cells and to characterize the effects of Jab1 silencing on prostate cancer cell growth and proliferation. Several stable cell lines have been established, and experiments are being conducted to characterize these cell lines. These works are currently being ... |
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| The Role of XMRV, a Novel Xenotropic Murine Retrovirus, in Human Prostate Cancers |
May 2011 |
27 pages |
| Authors:
Stephen P Goff; Jason Rodriguez; Ila Singh; Robert Schlaberg; Daniel Choe; Kristy Brown; Harsh Thaker; COLUMBIA UNIV NEW YORK
|
| Xenotropic murine leukemia virus related virus (XMRV) was recently discovered in human prostate cancers and is the first gammaretrovirus known to infect humans. While gammaretroviruses have well-characterized oncogenic effects in animals, they have not been shown to cause human cancers. We provide experimental evidence that XMRV is indeed a gammaretrovirus with protein composition and particle ultrastructure highly similar to Moloney murine leukemia virus (MoMLV). We analyzed 334 consecutive prostate resection ... |
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| Vaccination with Dendritic Cell Myeloma Fusions in Conjunction with Stem Cell Transplantation and PD-1 Blockade |
May 2011 |
10 pages |
| Authors:
David Avigan; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Most patients with multiple myeloma achieve a complete or near complete response following autologous transplantation. However, patients experience disease relapse from a persistent reservoir of chemotherapy resistant disease. There has been strong interest in developing immunotherapeutic strategies to eradicate residual disease following autologous transplantation. Our group has developed a tumor vaccine model whereby dendritic cells are fused with tumor cells. In clinical trials, vaccination with fusion cell results in anti-tumor ... |
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| Oxidative Lung Injury in Virus-Induced Wheezing |
May 2011 |
20 pages |
| Authors:
Roberto P Garofalo; TEXAS UNIV AT GALVESTON
|
| This project focuses on respiratory syncytial virus (RSV), the single most important pathogen causing acute respiratory-tract infections in children. RSV infections are a major precipitating factor of wheezing in asthmatic children, and they have been linked to both the development and the severity of asthma. Our group has established a multidisciplinary and highly integrated pre-clinical and translational research program that focuses on the role of oxidative injury in the pathogenesis ... |
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| Re-Writing the Histone Code of Breast Cancer Stem Cells |
May 2011 |
9 pages |
| Authors:
Brian D Strahl; Pilar Blancafort; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| The transcription factor SOX2 is a Cancer Stem Cell (CSC) marker that plays an pivotal role maintaining self-renewal in both embryonic and adult breast stem cells. In human embryonic stem cells SOX2 expression is down regulated by means of epigenetic mechanisms, including DNA methylation. SOX2 is overexpressed in many breast cancer cell lines as well as in poorly differentiated triple negative breast tumor specimens. Thus, enforced down-regulation of SOX2 in ... |
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| Purinergic Receptors in Quiescence and Localization of Leukemic Stem Cells |
May 2011 |
16 pages |
| Authors:
Byeong-Chel Lee; PITTSBURGH UNIV PA
|
| A small subpopulation of drug- and radiation-resistant leukemia is an immediate concern for leukemia patients as this subtype remains the actual cause of morbidity and mortality. Our preliminary results showed that P2Y14 functions in bone marrow to preserve stem progenitor cells from premature senescence/cell death induced by genotoxic stress. As P2Y14 is highly expressed in differentiation resistant leukemia cells, P2Y14 expression in leukemia cells may function in preserving regenerative capacity ... |
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| Small Molecule Activators of the TRK Receptors for Neuroprotection |
May 2011 |
15 pages |
| Authors:
Nicholas J Webster; Stan Krajewski; Michael C Pirrung; VETERANS MEDICAL RESEARCH FOUNDATION (VETERANS AFFAIRS) SAN DIEGO CA
|
| Our central hypothesis is that asterriquinone activators of the Trk receptors would prevent the neuronal cell death associated with traumatic brain injury and would improve cognitive and motor outcomes. We have developed agonists to TrkA and TrkB. The TrkA agonist has been tested in a preclinical model of cognitive impairment and a model of traumatic brain injury. The drug improves learning in a Morris water maze paradigm and reduces infarct ... |
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| Bio-Mechanical Interfaces for Cell-Based Microsystems |
22 APR 2011 |
18 pages |
| Authors:
Chad Mirkin; Aaron Dinner; Michael Roukes; Anthony Evans; Robert McMeeking; Christopher Chen; Milan Mrksich; CHICAGO UNIV IL
|
| The MURI represents a multidisciplinary program to develop hybrid microsystems that combine mammalian cells as functional components with conventional solid-state materials. Nanomechanical elements provide the interface between the adherent cells and materials, and are designed to transduce biological and mechanical signals at this interface. The first aim of the work has developed an integrated platform for installing mechanical interfaces to cells, including mechanical sensor and actuator arrays, surface chemistries to ... |
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| Plant Biofilm Inhibitors to Discover Biofilm Genes |
08 APR 2011 |
8 pages |
| Authors:
Thomas K. Wood; TEXAS ENGINEERING EXPERIMENT STATION COLLEGE STATION
|
| To control biofilms, we have synthesized the natural biofilm inhibitor (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone from the red alga Delisea pulchra and determined that it functions by disrupting quorum sensing in Vibrio harveyi by blocking all three channels of the V. harveyi quorum sensing system by rendering the quorum sensing master regulator protein LuxR unable to bind to the promoter sequences of quorum sensing-regulated genes. We have also discovered other inhibitors of cell signaling ... |
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| Solidago Vigaurea for Prostate Cancer Therapy |
APR 2011 |
73 pages |
| Authors:
Kounsouke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| Adenocarcinoma of the prostate is currently the most prevalent cancer in men in the United States and represents 36% of all cancers among men (1). It is estimated that more than 210,000 new cases are diagnosed and 32,000 patients succumb to this disease every year (1). Although patients with localized lesions can be cured by radical prostatectomy or radiotherapy, more than 90% of cancer deaths are attributed to metastatic disease ... |
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| The Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness |
APR 2011 |
150 pages |
| Authors:
Owen Hamill; TEXAS UNIV MEDICAL BRANCH AT GALVESTON
|
| A major challenge for treating prostate cancer (PC) is to discover new therapies that will prevent the spread of PC cells from the prostate to distal sites. Our research focuses on the stretch-activated mechanosensitive Ca2+ permeant channel (MscCa) as a central regulator of prostate tumor cell migration. Our experiments are designed to address the two most basic issues of the disease: the mechanism(s) that trigger progression of PC to malignancy ... |
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| Early Life Processes, Endocrine Mediators, and Number of Susceptible Cells in Relation to Breast Cancer Risk |
APR 2011 |
146 pages |
| Authors:
Dimitrios Trichopoulos; HARVARD COLL CAMBRIDGE MA
|
| The aim of the project was to investigate the role of early life processes, endocrine mediators and number of susceptible cells on adult life breast cancer risk. Based on the hypothesis that breast cancer risk is a function of number of mammary gland cells at risk of transformation and that this number is largely modulated by perinatal events and conditions, five component projects were initiated. The first three focused on ... |
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| WAVE3 Is a Biomarker for Breast Cancer Progression And Metastasis |
APR 2011 |
27 pages |
| Authors:
Khalid Sossey-Alaoui; CLEVELAND CLINIC FOUNDATION OH
|
| About one-third of patients with cancer have metastases that are detected at the time their cancer is first diagnosed, and an additional third of patients have metastases that are too small to be detected by usual diagnostic tests. These micrometastases, however, will eventually grow into clinically significant metastases if the patient receives no treatment or local treatment of the primary tumor only. Metastatic breast cancer is a disease with low ... |
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| Roles of SGK Isoform Signaling in Breast Cancer Migration and Invasion |
APR 2011 |
12 pages |
| Authors:
Jessica Gasser; HARVARD COLL CAMBRIDGE MA
|
| 14. ABSTRACT My experiments indicate that Serum and Glucocorticoid regulated Kinase (SGK) proteins facilitate breast cancer invasive migration, a critical step for ultimate cancer metastasis to other organs. The activation of SGK during cellular stress conditions, such as low oxygen found within a tumor, makes this data increasingly imperative for therapeutics. The research shown here demonstrates SGK loss in highly mestatic breast cancer cell lines causes an invasive migration defect. ... |
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| Role of the XIAP-Cooper Axis in Prostate Cancer |
APR 2011 |
21 pages |
| Authors:
Graham Brady; MICHIGAN UNIV ANN ARBOR
|
| We have identified, confirmed, and characterized a novel functional and physical interaction between the X-linked inhibitor of apoptosis (XIAP) and the copper chaperone for superoxide dismutase (CCS). We performed a targeted genetic screen in yeast to identify proteins involved in delivery of copper (Cu) to XIAP. This screen identified CCS as a primary mediator of Cu delivery to XIAP in yeast, and we subsequently determined that CCS delivers Cu to ... |
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| Role of Cyclin E as an Early Event in Ovarian Carcinogenesis |
APR 2011 |
40 pages |
| Authors:
Christine Walsh; CEDARS-SINAI MEDICAL CENTER LOS ANGELES CA
|
| At the genetic level, ovarian cancer is characterized by a large degree of genetic instability. High copy-number amplification at the CCNE1 (cyclin E) gene locus is the single most notable recurrent change, occurring in about 20% of tumors. We have hypothesized that CCNE1 gene amplification is an initiating event in the carcinogenic process of a subset of epithelial ovarian cancers. In the first two years of this award, we have ... |
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| Evaluating the Potential of Adipose Tissue-Derived MSCs as Anticancer Gene Delivery Vehicles to Bone-Metastasized Prostate Cancers |
APR 2011 |
16 pages |
| Authors:
Debasis Mondal; TULANE UNIV MEDICAL CENTER NEW ORLEANS LA
|
| Adipose tissue derived MSCs (AT-MSCs) have tumor-homing potential and can be used as anti-cancer gene delivery vehicles to prostate cancer (PCa). Our investigations have elucidated the role of factors released by both tumor cells and tumor-associated stromal cells, in increasing tran-endothelial migration (TEM) and tumor-site specific homing of AT-MSCs. We have identified several cell-surface markers that enable this phenotype of AT-MSCs, and have demonstrated a crucial role of the SDF-1/CXCR4 ... |
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| Mechanisms of Radiosensitization by the Neurotensin Receptor Antagonist SR48692 in Prostate Cancer Models |
APR 2011 |
19 pages |
| Authors:
Jaroslaw Dziegielewski; VIRGINIA UNIV CHARLOTTESVILLE
|
| This project tests the hypothesis that blocking neurotensin receptor 1 (NTR1) with a specific antagonist, SR48692, could sensitize prostate cancer to ionizing radiation, thus improving outcomes of radiotherapy. We demonstrated that SR48692 selectively sensitizes prostate cancer cells but not normal prostate epithelial cells, most plausibly due to the differences in NTR1 expression. We also observed drug-dependent radiosensitization in orthotopic xenografts of human prostate cancer cells in mice. Importantly, the sensitization ... |
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| Targeting the Reactive Stroma Niche in Prostate Cancer |
Apr 2011 |
9 pages |
| Authors:
David Rowley; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Rate of prostate cancer progression is affected by the reactive stroma microenvironment. Our previous studies have shown that reactive stroma is regulated by TGF-beta pathways. The objectives of the proposed research is to assess the origin/ Ontogeny of reactive stroma in cancer and fundamental mechanisms of recruitment/activation in prostate cancer. To date, we have addressed studies proposed for each Task. We have developed an in vivo matrix trapping approach to ... |
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| Development of a Multifaceted Ovarian Cancer Therapeutic and Imaging Agent |
Apr 2011 |
90 pages |
| Authors:
Francis S Markland; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| Ovarian cancer (OC) is the deadliest of all gynecological cancers, with five year survival rates of 45%. One critical feature of the disease is that two-thirds of the women diagnosed have advanced disease, and the five year survival rate of this group is 30%. This project outlines the development of a recombinant version of a member of a class of proteins known as disintegrins as an innovative imaging and diagnostic ... |
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| Targeting Neuropilin-1 in Prostate Cancer Bone Metastasis |
Apr 2011 |
195 pages |
| Authors:
Daqing Wu; EMORY UNIV ATLANTA GA
|
| The role of neuropilin-1 (NRP1) in the progression of human prostate cancer (PCa) remains unclear. This New Investigator Award is to investigate the signaling mechanism and targeting potential of NRP1 in PCa bone metastasis. During the entire period of award performance, we accomplished three major tasks: 1) Molecular mechanism of NRP1 signaling in bone metastatic PCa cells. We elucidated a novel signaling mechanism by which bone metastatic PCa cells acquire ... |
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| Materials to Engineer the Immune System |
Apr 2011 |
6 pages |
| Authors:
David Mooney; HARVARD COLL CAMBRIDGE MA
|
| The ex vivo manipulation of cells central to current approaches to cancer vaccines imposes a large economic and regulatory burden, dendritic cell modifications may be dependent on culture conditions and transient, and the vast majority of transplanted cells die following transplantation, leading to weak immune responses. The long-term objective is to bypass ex vivo cell manipulation in breast cancer vaccines, and instead develop effective material systems that program the immune ... |
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| TLK1 and Rad9 Cooperate in XRT-Refractory CaP |
Apr 2011 |
26 pages |
| Authors:
Arrigo De Benedetti; LOUISIANA STATE UNIV IN SHREVEPORT
|
| The main purpose of our work is to determine the expression pattern of TLKs and Rad9 in prostate cancer cell lines and in patients biopsies, and their relation to radiation resistance and (consequently) XRT failure. A second project was to identify compounds that inhibit the activity of TLKs and its phosphorylation of Rad9, and then determine the in vitro consequences of applying these compounds to the pattern of radiation sensitivity. ... |
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| Optimizing Treatment of Advanced Prostate Cancer and Exploiting Mechanisms Driving Castration Resistance |
Apr 2011 |
6 pages |
| Authors:
Elahe A Mostaghel; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
| Castration resistant prostate cancer (CRPC) ubiquitously displays increased expression of the AR and AR target genes, reflecting the critical importance of this pathway in prostate cancer progression. As novel agents which potently inhibit the AR pathway become clinically available, it will be critical to understand how severe shutdown of the AR pathway impacts tumor cell biology and how this will alter the natural history of CRPC. This proposal investigates the ... |
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| The Role of SF2 in Prostate Cancer Progression |
Apr 2011 |
32 pages |
| Authors:
Clay Comstock; JEFFERSON MEDICAL COLL PHILADELPHIA PA
|
| Prostate cancer (a leading cause of male mortality) development and progression is dependent upon androgen and androgen receptor (AR) signaling. Current therapies target androgen production and/or AR signaling. Evidence suggests that AR in some tumors may escape therapy through mechanisms that likely involve splicing. Purpose: To better understand splicing during prostate cancer development or progression. Scope: As outlined in the proposal (and recently published) observations suggest that the splicing factor ... |
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| Crosstalk Between Leptin Receptor and IGF-IR in Breast Cancer: A Potential Mediator of Chemoresistance |
Apr 2011 |
23 pages |
| Authors:
Rita Nahta; EMORY UNIV ATLANTA GA
|
| Obesity is a major risk factor for breast cancer, and is associated with reduced treatment response and reduced overall survival. The obesity-associated hormones IGF-I and leptin and their receptors, IGF-IR and leptin receptor (Ob-R), are elevated in breast cancer. Co-immunoprecipitation and immunoblotting demonstrated that IGF-IR and Ob-R interact in the breast cancer cell lines MDA-MB-231, MCF7, BT474, and SKBR3. Stimulation of cells with IGF-I promoted Ob-R phosphorylation, which was blocked ... |
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| Mesenchymal Stem Cells in the Bone Marrow Provide a Supportive Niche for Early Disseminated Breast Tumor-Initiating Cells |
Apr 2011 |
46 pages |
| Authors:
Carolyn Marsden; TULANE UNIV HEALTH SCIENCE CENTER NEW ORLEANS LA
|
| The study of breast cancer tumorigenesis and metastasis depends on the use of established breast cancer cell lines, which don t accurately represent the heterogeneity and complexity of human breast tumors. We developed a tumor model using primary breast tumor-initiating cells isolated from patient core biopsies which would more accurately reflect human breast cancer and its metastasis. Tumorspheres were successfully isolated from all patient core biopsies, independent of the ER/PR/Her2 ... |
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| Structural and Functional Analyses of the Six1 Transcriptional Complex for Anti-Breast Cancer Drug Design |
Apr 2011 |
49 pages |
| Authors:
Heide Ford; COLORADO UNIV AURORA CO
|
| Cancer and normal development share many properties. During normal development, genes are activated that stimulate proliferation, migration, invasion, vascularization, and that alter cell survival. These gene products are often lost once organ development is complete. In cancer, many developmental genes are re-activated, stimulating the aforementioned processes out of context. The Six1 gene encodes a transcription factor that induces the expression of a large number of genes that are involved in ... |
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| Regulation of Cell Migration in Breast Cancer |
Apr 2011 |
13 pages |
| Authors:
Reyda Gonzalez-Nieves; JACKSON (HENRY M) FOUNDATION BETHESDA MD
|
| Cell migration is an essential cellular process and deregulation of this process may result in serious consequences such as tumor metastasis. Numerous studies have demonstrated that the IPP complex is linked to cell adhesion and cell migration. Our lab has found that Rsu-1 binds to the IPP complex through PINCH1 5 and the absence of either Rsu-1 or PINCH! proteins results in a change in epithelial cell migration. In addition, ... |
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| Epigenetic Mechanisms of Folate Nutrition in Breast Cancer |
Apr 2011 |
9 pages |
| Authors:
Rebecca Lobo; CALIFORNIA UNIV DAVIS
|
| The most significant finding in this research period has been that making breast cancer cells folate deficient is difficult to do without killing the cells. It is much easier to target folate and one carbon metabolism in different ways such as inhibiting key enzymes with either miRNA or drugs. This is the rationale for why we have switched to making tetracycline inducible stably transduced cell lines that express miRNA against ... |
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| Telomerase as an Androgen Receptor-Regulated Target in Selenium Chemoprevention of Prostate Cancer |
Apr 2011 |
25 pages |
| Authors:
Shuang Liu; TULANE UNIV NEW ORLEANS LA
|
| The project is to investigate telomerase as a potential target of AR signaling suppression by selenium. We found that overexpression of hTERT attenuates the apoptosis inducing activities of selenium, supporting an important role of hTERT in selenium action in prostate cancer cells. More importantly, we found that combination of selenium and bicalutamide produce a robust down-regulation of androgen receptor (AR) signaling, hTERT expression and telomerase activity. Furthermore, apoptosis induction by ... |
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| The Role Of Rho GTPases In Breast Cancer Migration And Invasion |
Apr 2011 |
6 pages |
| Authors:
Jeffery Smith; SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
|
| Rho-family GTPases are the major regulators of the actin and microtubule cytoskeleton. Regulators of the GTPases include GEFs and GAPs, which control activation and deactivation, respectively, of this family of molecular switches. This study explores the role of the GEF Tiam2 in breast cancer cell proliferation and invasion, which was initially discovered using a siRNA screen in MDA-MB-231 breast cancer cells. Protein expression studies are performed using a panel of ... |
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| Chemical Agonists of the PML/Daxx Pathway for Prostate Cancer Therapy |
Apr 2011 |
26 pages |
| Authors:
John Reed; BURNHAM INST LA JOLLA CA
|
| Metastatic, hormone refractory prostate cancer is currently an incurable disease. Consequently, novel therapeutic agents are needed that promote killing of malignant prostate cancer cells in a more efficient, less toxic manner. The goal of this project was to identify chemicals that activate an endogenous anti-cancer mechanism that induces tumor cell suicide and auto-destruction. To achieve this goal, we focused on an intrinsic tumor suppressor system involving the proteins PML and ... |
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| Cell Fusion as a Cause of Prostate Cancer Metastases |
Apr 2011 |
25 pages |
| Authors:
Yuri Lazebnik; COLD SPRING HARBOR LAB NY
|
| The main goal of the study funded by this grant was to test a hypothesis that cell fusion between tumor cells, or between tumor and normal cells, contributes to metastasis. This hypothesis suggests that cell fusion contributes to carcinogenesis through two mechanisms: by generating cells with diverse genetic and epigenetic properties and by providing tumor cells with qualities of normal cells that are required to travel throughout the body while ... |
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| Hydrogen-bonded LbL Shells for Living Cell Surface Engineering |
21 Mar 2011 |
11 pages |
| Authors:
Veronika Kozlovskaya; Svetlana Harbaugh; Irina Drachuk; Olga Shchepelina; Nancy Kelley-Loughnane; Morley Stone; Vladimir V Tsukruk; AIR FORCE RESEARCH LAB WRIGHT-PATTERSON AFB OH HUMAN EFFECTIVENESS DIRECTORATE
|
| We report on the design of cytocompatible synthetic shells from highly permeable, hydrogen-bonded multilayers for cell surface engineering with preservation of long-term cell functioning. In contrast to traditional polyelectrolyte layer-by-layer (LbL) systems, shells suggested here are based on hydrogen bonding allowing gentle cell encapsulation using non-toxic, non-ionic and biocompatible components such as poly(N-vinylpyrrolidone) (PVPON) and tannic acid (TA) which were earlier exploited on abiotic surfaces but never assembled on cell ... |
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| Using Human Stem Cells to Study the Role of the Stroma in the Initiation of Prostate Cancer |
MAR 2011 |
35 pages |
| Authors:
Gail Risbridger; MONASH UNIV CLAYTON (AUSTRALIA)
|
| This project aimed to determine the role of tumor stroma in prostate cancer biology. To do this, we used a model of human embryonic stem cell (hESC) differentiation that was established in our laboratory. Using hESC-derived prostatic epithelial cells, we attempted to determine whether or not tumor stroma derived from human prostate cancer specimens induce and initiate carcinogenesis. The data generated in this funded project failed to support the hypothesis ... |
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| Identification and Therapeutic Targeting of Paracrine Senescence Factors in the Prostate Tumor Microenvironment |
MAR 2011 |
32 pages |
| Authors:
James Dean; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
| Deaths due to prostate cancer- the second leading cause of cancer death in men in the United States - could be prevented with more effective treatments. Overcoming tumor cell resistance to the effects of androgen deprivation and chemotherapies would significantly improve the morbidity and mortality of prostate cancer. We hypothesize that the induction of cellular senescence in the tumor microenvironment by androgen deprivation and cytotoxic chemotherapy promotes the resistance and ... |
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| Screening and Selection of New Antagonists of the RING-Mediated Hdm2/Hdmx Interaction |
MAR 2011 |
126 pages |
| Authors:
Julio A. Camerero; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| During the first period of the grant we have been able: 1) Produce large libraries (106 different cyclotides) of cyclotides in E. coli cells using the loop 2 of the cylotide MCoTI-I (Specific aim #1, Task 2a) 2) We have cloned, expressed and characterized a fluorogenic reporter to screen in-cell cyclotide libraries for inhibitors of the RING-mediated interaction between Mdm2/MdmX (specific aim #1, Task 1a & 1b). |
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| Control of Disease Recurrence by Tumor-Infiltrating T Cells in Ovarian Cancer |
Mar 2011 |
36 pages |
| Authors:
Brad Nelson; BRITISH COLUMBIA CANCER AGENCY VANCOUVER
|
| Ovarian cancer patients with large numbers of T cells in their tumor live longer after chemotherapy compared to patients with fewer T cells in their tumor. Our goal is to use modern genomic techniques to identify the antigens recognized by these T cells, with an emphasis on new antigens that arise during chemotherapy. To this end, we are collecting matched primary and recurrent tumor tissue from ovarian cancer patients (Tasks ... |
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| A Biophysico-Computational Perspective of Breast Cancer Pathogenesis and Treatment Response |
Mar 2011 |
263 pages |
| Authors:
Valerie Weaver; CALIFORNIA UNIV SAN FRANCISCO
|
| The extracellular matrix (ECM) regulates breast homeostasis and is corrupted in breast cancers. We showed that the breast ECM progressively reorganizes into large bundles and stiffens due to high activity of ECM remodeling and cross-linking enzymes such as lysyl oxidase (LOX. The functional relevance of this was revealed through in vitro and in vivo work which revealed that ECM stiffness enhances breast cell growth, survival, migration and regulates treatment responsiveness ... |
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| Estrogen Receptor/MAPK Crosstalk as a Mechanism of Radiation Resistance of Breast Cancer |
Mar 2011 |
19 pages |
| Authors:
Anupama Munshi; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Loss of estrogen receptor (ER) function has been associated with hyperactive ERK1/2, which culminates in aggressive, radiation resistant cancers. The ERK1/2 pathway has also been linked to DNA damage and repair, with multiple proteins involved in DNA repair being transcriptionally regulated through ERK1/2-dependent signaling. An increased DNA repair capacity in ER- negative breast tumors has bee implicated as a mechanism of radioresistance. We postulate that the mechanism of development of ... |
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| Use of Synthetic Antibodies Targeted to the Jak/Stat Pathway in Breast Cancer |
Mar 2011 |
11 pages |
| Authors:
Charles Clevenger; Anthony Kossiakoff; NORTHWESTERN UNIV EVANSTON IL
|
| This proposal seeks to generate SABs (synthetic antigen binders) against the PRLr (prolactin receptor) signaling complex to systematically inhibit and modulate its important activities in breast cancer. This complex has clearly been demonstrated to play a significant role in the development and spread of this disease, and yet the generation of pharmacologic agents that can specifically block their function has been slow. We hypothesize that SABs can be rapidly generated ... |
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| Combinatorial Targeting of Prostate Carcinoma Cells and Tumor Associated Pericytes with Antibody-Based Immunotherapy and Metronomic Chemotherapy |
Mar 2011 |
9 pages |
| Authors:
Soldano Ferrone; Barbara Foster; Michael Moser; PITTSBURGH UNIV PA
|
| Seventy seven 10 week old TRAMP mice were enrolled in the study. Administration of metronomic chemotherapy with cyclophosphamide and AN2 crossreacting mAb 225.28 or isotype control mAb F3- C25 was well tolerated. The therapy reduced disease burden and the severity of the disease. The findings from these studies support development of metronomic chemotherapy for the treatment of progressive disease (men with a rising PSA), aggressive forms of the disease and ... |
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| Articular Cartilage Repair Through Muscle Cell-Based Tissue Engineering |
Mar 2011 |
86 pages |
| Authors:
Johnny Huard; CHILDREN'S HOSPITAL OF PITTSBURGH PA
|
| Using the modified preplate technique, we have isolated a population of early myogenic progenitor cells from postnatal skeletal muscle that display stem cell characteristics. We have shown that these muscle-derived stem cells (MDSCs) can differentiate toward myogenic, osteogenic, chondrogenic, neurogenic, and hematopoietic lineages. Specifically, MDSCs cultured in chondrogenic medium can undergo chondrogenic differentiation in vitro, and MDSCs delivered to osteochondral defects display good cell survival and can differentiate into chondrocytes ... |
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| Modulation of Stem Cell Differentiation and Myostatin as an Approach to Counteract Fibrosis in Muscle Dystrophy and Regeneration after Injury |
Mar 2011 |
58 pages |
| Authors:
Nestor Gonzalez-Cadavid; CHARLES R DREW UNIV OF MEDICINE AND SCIENCE LOS ANGELES CA
|
| In Year 4 the in vivo studies to determine the relative capacity of the wild type muscle derived stem cells (WT MDSC) and their counterparts lacking myostatin obtained from the mouse with genetic inactivation of myostatin (Mst KO MDSC), to repair the notexin-injured gastrocnemius in aged mdx mice, were completed. These aged mice show exacerbated bouts of necrosis and lipofibrotic degeneration that mimic a mild form of Duchenne s muscular ... |
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| 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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| The Role of Tim50 in Chemoresistance and Oncogenesis of Breast Cancer |
FEB 2011 |
15 pages |
| Authors:
Heidi Sankala; VIRGINIA COMMONWEALTH UNIV RICHMOND
|
| To investigate how gain of function p53 mutants exert their oncogenic effects, protein expression was compared between a p53 null cell line stably expressing vector alone or the p53 gain of function mutants, p53-R175H and -R273H. One protein that was upregulated in cells expressing the p53 gain of function mutants control cell lines was identified by mass spectrometry as translocator of the mitochondrial membrane 50 (Tim50). p53-R175H and -R273H, but ... |
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| Characterization of Neurofibromas of the Skin and Spinal Roots in a Mouse Model |
FEB 2011 |
160 pages |
| Authors:
Yuan Zhu; MICHIGAN UNIV ANN ARBOR
|
| Benign neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs) contribute to the majority of morbidity and mortality associated with NF1. The proposed studies are attempting to provide insights into one of the fundamental questions in neurofibroma biology: whether bi-allelic NF1 inactivation is necessary for neurofibroma formation. The objectives of this proposal are to use a series of newly established mouse models to (1) identify and characterize neurofibromas that are exclusively ... |
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| Examination of Knock Out Mutants for Sensitivity to Phloroglucinol |
Feb 2011 |
5 pages |
| Authors:
Karen M Frost; DRATHS CORP OKEMOS MI
|
| Progress relates to Deliverable # 1: Identification of the proteins involved in export of phloroglucinol and determination of whether overexpression of these proteins increases the concentration and yield of microbe-synthesized phloroglucinol. Using transcriptome analysis, candidate genes were identified that may be involved in the export of phloroglucinol from the inside of the Escherichia coli catalyst to the culture medium. Gene expression in non-phloroglucinol synthesizing E. coli W3110 serA(DE3)/pBCl.l46 was compared ... |
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| Enhancement of Vitamin D Action in Prostate Cancer through Silencing of CYP24 |
Feb 2011 |
42 pages |
| Authors:
Dolores Lamb; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| This study focuses on the enzyme, CYP24 which hydroxylates vitamin D acting to catalyze the first step in the breakdown of Vitamin D, effectively limiting this growth inhibitory signaling pathway. We are testing the hypothesis that through the inhibition of CYP24 using an siRNA approach we can convert prostate cancer cells that are resistant to the antiproliferative actions of Vitamin D to cells that are growth inhibited at low concentrations ... |
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CELLS(BIOLOGY)
