| Adoptive Immunotherapy Combined with Hematopoietic Cell Transplantation as a Therapeutic Treatment of Prostate Cancer |
Jul-2009 |
19 pages |
| Authors:
Beatrice Knudsen; Scott S Graves; Rainer Storb; Bradley Stone; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
 | We determined that a prostate cell lysate prepared from canine prostate tissue was immunogenic when injected in female dogs. In addition to the known prostate antigen, canine prostate specific esterase (CPSE), we identified by molecular weight several other proteins against which the dog made IgG antibodies. Using a mixed lymphocyte reaction, we found that a cellular response was generated against the prostate cell lysate after the female dog was injected ... |
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| Adoptive Immunotherapy Combined with Hematopoietic Cell Transplantation as a Therapeutic Approach to Treatment of Prostate Cancer |
Oct-2008 |
14 pages |
| Authors:
Beatrice Knudsen; Scott S Graves; Rainer Storb; Bradley Stone; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
| We determined that cell lysates prepared from canine prostate tissue was immunogenic when injected in female dogs. In addition to the known prostate antigen, canine prostate specific esterase (CPSE), we identified by molecular weight several other proteins against which the dog made IgG antibodies. Using a mixed lymphocyte reaction, we found that a cellular response was generated against the prostate cell lysate after the female dog was injected 3 times ... |
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| The Bone Marrow Stem Cell Origin of Human Breast Cancer Using Transgenic Mouse Models |
Oct-2008 |
13 pages |
| Authors:
Sanford H Barsky; OHIO STATE UNIV RESEARCH FOUNDATION COLUMBUS
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| There is emerging evidence that transformed stem cells may be the source of human cancers. We felt that transgenic mouse models were ideally suited to examine this question and proposed to conduct marrow transplant experiments to test whether marrow stem cells are the cells of breast cancer origin. Our most significant findings included: 1) the demonstration that stromal cells within the transgenic breast cancers contain significant percentages of tissue macrophages, ... |
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| Impact of Radiation on Blood Cell Deformability |
19-Sep-2008 |
15 pages |
| Authors:
James C Sturm; Robert H Austin; PRINCETON UNIV NJ OFFICE OF RESEARCH AND PROJECT ADMINISTRATION
|
| This project had two exploratory goals. The first is the investigation the effect of radiation on the deformability of blood cells, as detected by novel microfluidic chips. The long-term goal would be to have a rapid low-cost method to screen people for exposure to radiation. For this project we have developed chips to measure deformability of both red and white blood cells in human blood, and observed an effect from ... |
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| Enhanced Eradication of Lymphoma by Tumor-Specific Cytotoxic T Cells Secreting an Engineered Tumor-Specific Immunotoxin |
01-Jun-2008 |
10 pages |
| Authors:
BAYLOR COLL OF MEDICINE HOUSTON TX CELL AND GENE CENTER
|
| In this project we propose to use tumor-specific T cells to produce an immunotoxin (IT) targeting tumor cells only when these T cells are specifically activated by the tumor. We use lentiviral vectors to modify tumor specific T cells with our immunotoxin. PEA based immunotoxins affect cell viability by ADP ribozilation of their elongation factor-2. To produce high titer of vector encoding the IT we needed to generate a producer ... |
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| Functional CD8+ T Cell Responses in Lethal Ebola Virus Infection |
15 MAR 2008 |
10 pages |
| Authors:
Steven B. Bradfute; Kelly L. Warfield; Sina Bavari; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Ebolavirus (EBOV) causes highly lethal hemorrhagic fever that leads to death in up to 90% of infected humans. EBOV infection induces massive lymphocyte apoptosis, which is thought to prevent a functional adaptive immune response. In addition, in vitro studies show that EBOV induces aberrant responses in dendritic cells, which is thought to contribute to a failed adaptive immune response. In this study we show that in a lethal mouse model ... |
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| HLA Typing for Bone Marrow Transplantation |
31 OCT 2007 |
18 pages |
| Authors:
Michelle Setterholm; Judy W. Davis; Steve M. Spellman; NATIONAL MARROW DONOR PROGRAM MINNEAPOLIS MN
|
| Task 1 : Evaluate optimal short term storage parameters for stimulated and unstimulated leukapheresis (donor lymphocytes) and bone marrow products, including the type of storage media and the cell concentration, in addition to temperature and duration of storage before processing or infusion. Task 2: The NMDP has developed an algorithm that "predicts' high resolution HLA typing results on donor samples that exist in the Registry with only low or intermediate ... |
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| Novel MHC Class II Breast Cancer Vaccine Using RNA Interference (RNAi) to Down Regulate Invariant Chain (Ii) |
01-May-2007 |
218 pages |
| Authors:
James A Thompson; MARYLAND UNIV BALTIMORE COUNTY BALTIMORE MD
|
| Our goal is to induce a strong CD4+ T cell response against tumor antigens by preferentially presenting endogenous tumor antigens via class II major histocompatibility complex molecules (MHC II). MHC II can present endogenous tumor antigens if expressed in the absence of Invariant chain (II). We have up-regulated MHCII and down regulated II without affecting MHC II expression in tumor cells. Using the key transcription factor class II trans-activator (CIITA) ... |
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| Quarterly Performance/Technical Reports: HLA Typing for Bone Marrow Transplantation, and Development of Medical Technology for Contingency Response to Marrow Toxic Agents |
31 MAR 2007 |
44 pages |
| Authors:
Patricia A. Coppo; Judy W. Davis; Steve M. Spellman; NATIONAL MARROW DONOR PROGRAM MINNEAPOLIS MN
|
| N00014-05-1-0310: Task 1: Evaluate optimal short term storage parameters for stimulated and unstimulated leukapheresis (donor lymphocytes) and bone marrow products, including the type of storage media and the cell concentration, in addition to temperature and duration of storage before processing or infusion. Task 2: The NMDP has developed an algorithm that "predicts" high resolution HLA typing results on donor samples that exist in the Registry with only low or intermediate ... |
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| Are Anti-Inflammatory Lymphocytes Able to Induce Remission of Breast Cancer. Addendum |
FEB 2007 |
|
| Authors:
Susan E. Erdman; MASSACHUSETTS INST OF TECH CAMBRIDGE
|
 | Recent studies suggest that inflammation is a key contributor to development of breast cancer in women. Increasing scientific and medical data point to immune cells in particular pro-inflammatory CD4+ effector (TE) cells and anti-inflammatory CD4+regulatory (TR) cells as pivotal mediators in human health and disease. We have previously demonstrated that anti- inflammatory TR cells prevent colorectal cancer (CRC) in mice by suppressing inflammatory growth factors. We show here that transfer ... |
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| HLA Typing for Bone Marrow Transplantation |
31 JAN 2007 |
4 pages |
| Authors:
Patricia A. Coppo; Judy W. Davis; Steve M. Spellman; NATIONAL MARROW DONOR PROGRAM MINNEAPOLIS MN
|
| Task 1 : Evaluate optimal short term storage parameters for stimulated and unstimulated leukapheresis (donor lymphocytes) and bone marrow products, including the type of storage media and the cell concentration, in addition to temperature and duration of storage before processing or infusion. Task 2: The NMDP has developed an algorithm that "predicts' high resolution HLA typing results on donor samples that exist in the Registry with only low or intermediate ... |
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| Telomere Length as a Predictor of Aggressive Prostate Cancer |
NOV 2006 |
10 pages |
| Authors:
Elizabeth A. Platz; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
|
| We are evaluating whether men with shorter telomere length in prostate cancer tissue and in normal appearing prostate tissue adjacent to adenocarcinoma have a higher risk of aggressive prostate cancer than men with longer telomere length. Since the last progress report (Nov 2005) the tissue microarrays were assembled by our Harvard collaborators. At Hopkins, we completed staining of the tissue microarrays for telomere length and are in the processing of ... |
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| Racial Differences in Lifestyle Modification in Men with Newly-Diagnosed Prostate Cancer |
JUL 2006 |
10 pages |
| Authors:
Jessie A. Satia; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| The purpose of this investigation is to determine whether men diagnosed with prostate cancer make changes in dietary intake, physical activity, and use of dietary supplements, and the extent to which these changes differ by race (African American versus Caucasian American). The study also seeks to determine whether alterations in dietary intake and dietary supplement use among prostate cancer patients are associated with changes in oxidative DNA damage in lymphocytes ... |
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| Human Prostate Cancer Infiltrating Lymphocytes: Raft Microdomains, Signaling and Activation in Organ Cultures |
JUN 2006 |
37 pages |
| Authors:
Antonella Viola; INSTITUTO VENETO DI MEDICINA MOLECOLARE PADOVA (ITALY)
|
| Prostate cancer is the second leading cause of malignancy-related mortality in males in the Western world. While radical prostatectomy and local radiotherapy are largely successful for patients with localized cancer, available treatments for metastatic prostate carcinoma have demonstrated weak curative efficacy. Thus, androgen reduction often results in the selection of hormone-resistant clones, which seem to be also resistant to radiotherapy or chemotherapy. It is therefore necessary to find alternative therapeutic ... |
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| Quarterly Performance/Technical Report of the National Marrow Donor Program |
01 MAY 2006 |
37 pages |
| Authors:
Patrica A. Coppo; Judy W. Davis; Steve M. Spellman; NATIONAL MARROW DONOR PROGRAM MINNEAPOLIS MN
|
| Contract N00014-05-1-0859: 1. Contingency Preparedness: Collect information from transplant centers build awareness of the Transplant Center Contingency Planning Committee and educate the transplant community about the critical importance of establishing a nationwide contingency response plan. 2. Rapid Identification of Matched Donors : Increase operational efficiencies that accelerate the search process and increase patient access are key to preparedness in a contingency event. 3, Immunogenetic Studies: Increase understanding of the immunologic ... |
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| DNA Repair Gene Polymorphisms in Hereditary and Sporadic Breast Cancer |
MAR 2006 |
33 pages |
| Authors:
Luisel Ricks-Santi; GEORGETOWN UNIV WASHINGTON DC
|
| Genetic breast cancer risk factors for sporadic and familial breast cancer may be elucidated through studies of women with BRCA1 mutations or in women in high risk breast/ovarian cancer families. There is variable penetrance for breast cancer among women in families with known BRCA1 mutations, and we hypothesize that this might be due to genetic variants in wild-type BRCA1 or other DNA repair genes and we hypothesized that these genetic ... |
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| Evaluation of the Effects of Multiple Immunizations Administered in a Stressful Environment on Immunologic Function |
MAR 2006 |
11 pages |
| Authors:
Kevin L. Russell; Margaret A. K. Ryan; NAVAL HEALTH RESEARCH CENTER SAN DIEGO CA
|
| It is hypothesized that multiple vaccinations administered simultaneously in a stressful environment may induce an exaggerated Th2 immune response and adverse health effects. Epidemiological surveys have preliminarily confirmed adverse health effects but not Th2 immune responses in multiply immunized war veterans. We propose a prospective clinical trial in a military recruit population ( ~ 6 5 0t)o test the hypothesis that multiple, simultaneous vaccinations in a stressful environment induce an ... |
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| Effects of Hematopoietic Stem Cell Age on CML Disease Progression |
MAR 2006 |
9 pages |
| Authors:
Kenneth Dorshkind; CALIFORNIA UNIV LOS ANGELES
|
| CML results from a chromosomal translocation in hematopoietic stem cells (HSC), yet the disease primarily presents as a myeloid hyperplasia with relatively infrequent lymphoid involvement. We proposed that age-associated defects in the potential of HSC to generate lymphocytes underlies this presentation. The results at the time of this writing support this hypothesis. Bone marrow cells from young and old mice were transduced with a retrovirus carrying the BCR-ABL 9:22 chromosomal ... |
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| Mutagen Sensitivity, Apoptosis, and Polymorphism in DNA Repair as Measures of Prostate Cancer Risk |
FEB 2006 |
150 pages |
| Authors:
Radoslav Goldman; GEORGETOWN UNIV WASHINGTON DC
|
| Prostate cancer is the most common lethal tumor among US males but etiology of the disease remains unknown. We hypothesize that low DNA repair contributes to increased risk of having prostate cancer. To evaluate the hypothesis, we conducted a case-control study of prostate cancer evaluating association of mutagen sensitivity phenotype with cancer risk. We established a repository of fully annotated specimen of 63 prostate cancer cases and 109 controls frequency ... |
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| Population Based Assessment of MHC Class 1 Antigens Down Regulation as Marker in Increased Risk for Development and Progression of Breast Cancer From Benign Breast Lesions |
JAN 2006 |
42 pages |
| Authors:
Maria J. Worsham; HENRY FORD HEALTH SYSTEM DETROIT MI
|
| Despite advances in chemotherapy and radiation therapies, advanced breast cancer still carries a high mortality rate. The need for effective therapies is urgent. The overall aim of this research proposal is to recognize early markers of disease and their interaction with other epidemiological risk factors that can serve as risk indicators for subsequent development of breast cancer from precancerous lesions and as prognostic markers for progression from primary to metastatic ... |
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| Randomized Trial of Interleukin-2 IL-2) as Early Consolidation Following Marrow Ablative Therapy with Stem Cell Rescue for Metastatic Breast Cancer |
OCT 2005 |
8 pages |
| Authors:
Wolfram E. Samlowski; UTAH UNIV SALT LAKE CITY
|
| Interleukin-2 (IL-2) has the capacity to activate lymphocytes to kill multi-drug resistant cancer cells. Our phase I data established the feasibility of administering a single course of low-dose IL-2 (1.6 million 1U/m2/day as a continuous i.v. infusion for 18 days) as consolidation treatment to patients with metastatic breast cancer early after intensive chemotherapy. We are performing a phase I1 trial of AC+T chemotherapy followed by IL-2 consolidation (1 cycle as ... |
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| Cytolytic T Lymphocytes in Organotypic Breast Carcinoma Culture |
OCT 2005 |
12 pages |
| Authors:
Dorothee Herlyn; PENNSYLVANIA UNIV PHILADELPHIA WISTAR INST
|
| In the proposed studies, novel T cell immunotherapies against breast cancer will be developed based on studies demonstrating a positive correlation between T lymphocytic infiltration of these tumors and favorable clinical outcome. The major goal of the proposed studies is to isolate and characterize cytolytic T lymphocytes (CTL) with in vivo-like T cell receptors. The CTL provide the basis for adoptive CTL immunotherapy and active immunotherapy with CTtderived peptides/antigens. During ... |
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| Tumor Immunity by Hydrophobic Bearing Antigens |
14 SEP 2005 |
30 pages |
| Authors:
Constantin G. Ioannides; M D ANDERSON CANCER CENTER HOUSTON TX
|
| CD8+ cells expressing high numbers of TCR per cell (TCRhi) are important mediators of anti-tumor effects. To understand the relationship between TCR density and Ag affinity for TCR in the outcome of differentiation of CTL recognizing tumor Ag, we analyzed perforin induction in ovarian tumor-associated lymphocytes in response to the smallest possible changes in the atomic forces of interaction between Ag and TCR. Stimulating undifferentiated, apoptosis-resistant CD8+ cells expressing high ... |
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| The Antemortem Detection and Conformational Switches of Prion Proteins |
JUL 2005 |
30 pages |
| Authors:
David R. Schubert; Yuanbin Liu; Roland Riek; SALK INST FOR BIOLOGICAL STUDIES LA JOLLA CA
|
| Blood from animals with prion disease contain low levels of prion infectivity, which primarily resides in the "buffy coat" fraction that contains lymphocytes and mononuclear cells. We believe that detecting individual infected white blood cells (WBCs) may increase the detection sensitivity by over 100-fold when compared with a method using pooled cells. We have developed a method that combines WBC isolation and cell blotting of PrP(Sc) to detect individual cells ... |
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| Evaluation of Feasibility for a Case-Control Study of Adrenal Androgen Production in Postmenopausal Women With Breast Cancer |
JUL 2005 |
6 pages |
| Authors:
Joanne F. Dorgan; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| Postmenopausal women with elevated serum estrogens and androgens are at an increased risk of breast cancer. Dehydroepiandrosterone sulfate (DHEAS) is secreted only by the adrenals, and elevated serum DHEAS levels in postmenopausal women who develop breast cancer suggest increased adrenal androgen production. The objective of the pilot study is to evaluate the feasibility of conducting a case-control study that uses adrenocorticotropic hormone (ACTH) stimulation tests to determine if postmenopausal women ... |
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| Phase II Study of HER-2/Neu Intracellular Domain Peptide-Based Vaccine Administered to Stage IV HER2 Positive Breast Cancer Patients Receiving Trastuzumab |
MAY 2005 |
8 pages |
| Authors:
Mary L. Disis; SEATTLE UNIV WA
|
| The cytotoxic T lymphocyte (CTL) has been considered the primary immune effector involved in mediating an anti-tumor response. Recent studies have demonstrated that "sensitization" of HER2 overexpressing tumor cells with trastuzumab, in vitro, will enhance the function of CTL specific for HER2. We have completed a Phase I study of a MER2 peptide based vaccine in women with HSR2 overepxressing breast cancers without toxicity, particularly autoimmune or cardiac toxicity. This ... |
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| Sleep Deprivation in Humans, Immunodepression and Glutamine Supplementation |
15 APR 2005 |
77 pages |
| Authors:
Linda M. Castell; Elizabeth Gough; Rebecca Cardenas; James c. Miller; OXFORD UNIV (UNITED KINGDOM)
|
| This report results from a contract tasking University of Oxford as follows: The Grantee will investigate the immunological response of subjects to one night of sleep deprivation with respect to the following areas (I) Are the cytokines linked with eosinophils neutrophils and lymphocytes cell types which are known to be affected by sleep deprivation changed in terms of intracellular cytokine production? (2) What is the psychoneurological link between the apparent ... |
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| Homeostatic T Cell Expansion to Induce Anti-Tumor Antoimmunity in Breast Cancer |
APR 2005 |
30 pages |
| Authors:
Robert G. Baccale; SCRIPPS RESEARCH INST LA JOLLA CA
|
| We have previously shown using a mouse model of melanoma that homeostatic T-cell proliferation, a process occurring in response to lymphopenia and dependent on signaling by self-peptide/MHC and trophic cytokines, may promote effective anti-tumor autoimmunity if induced in conjunction with a tumor-cell challenge. We are currently investigating whether this principle can be applied to mouse models of advanced breast carcinoma, and whether the anti-tumor response can be enhanced using selected ... |
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| Intracellular Survival of Campylobacter jejuni in Human Monocytic Cells and Induction of Apoptotic Death by Cytholethal Distending Toxin |
30 MAR 2005 |
5 pages |
| Authors:
Thomas E. Hickey; Gary Majam; Patricia Guerry; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
|
| Campylobacter jejuni 81-176 is capable of extensive replication within human monocytic cell vacuoles and induces apoptotic death via cytolethal distending toxin. |
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| Tumor-Mediated Suppression of Dendritic Cell Vaccines |
MAR 2005 |
37 pages |
| Authors:
Emmanuel Akporiaye; ARIZONA UNIV TUCSON
|
| The unique ability of dendritic cells to potently stimulate lymphocytes in an antigen-specific fashion has made them prime candidates for cancer immunotherapy. A number of tumor-derived products have been suggested to promote tumor establishment and progression by interfering with DC functions. One of the best characterized of these factors is Transforming growth factor- beta (TGF-beta), a multifunctional cytokime that exerts potent suppressive effects on cells of the immune system. TGF-beta ... |
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| Mutagen Sensitivity, Apoptosis, and Polymorphism in DNA Repair as Measures of Prostate Cancer Risk |
FEB 2005 |
116 pages |
| Authors:
Radoslav Goldman; GEORGETOWN UNIV WASHINGTON DC
|
| This proposal evaluates interindividual differences in the response to genotoxic stress as prostate cancer risk factors. To this end we use measurements of mutagen sensitivity, apoptosis, comet assay, and single nucleotide polymorphisms in DNA repair genes OGG1 and XRCC1. These biomarkers are evaluated in 100 prostate cancer cases and 100 controls matched on age and race in order to measure response to bleomycin exposure is short-term cultured lymphocytes to define ... |
|
| Radiation-Induce Immune Modulation in Prostate Cancer |
JAN 2005 |
87 pages |
| Authors:
William H. McBride; CALIFORNIA UNIV LOS ANGELES
|
| This proposal is designed to determine if radiation therapy inhibits presentation of prostate tumor antigens through the endogenous pathway by dendritic cells (DC) and to devise strategies to overcome this inhibition. This functional immune suppression following radiation therapy is not associated with cell killing but rather by interference with antigen processing. In this regard it is very different from the conventional view of immune suppression associated with lymphocyte sensitivity to ... |
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| Randomized Trial in Interleukin-2 (IL-2) as Early Consolidation Following Marrow Ablation Therapy with Stem Cell Rescue for Metastatic Breast Cancer |
OCT 2004 |
9 pages |
| Authors:
Wolfram E. Samlowski; Finn B. Peterson; UTAH UNIV SALT LAKE CITY
|
| Interleukin-2 (IL-2) has the capacity to activate lymphocytes to kill multidrug resistant cancer cells. Our phase I data established the feasibility of administering a single course of low-dose IL-2 (1.6 million IU/m2/day as a continuous i.v. infusion for 18 days) as consolidation treatment to patients with metastatic breast cancer early after intensive chemotherapy. Seven patients (60%) remained in complete remission at a median of >435 days post stem cell transplantation. ... |
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| Hypertonic Saline Resuscitation Modulates Neutrophil Adhesion Molecule Expression of Post-Traumatic Hemorrhagic Shock Patients |
01 SEP 2004 |
13 pages |
| Authors:
Sandro B. Rizoli; Shawn G. Rhind; Pang N. Shek; Kenji Inaba; Dennis Filips; Homer Tien; Fred Brenneman; Ori D. Rotstein; SUNNYBROOK AND WOMENS COLL HEALTH SCIENCES CENTER TORONTO (ONTARIO)
|
| Fluid resuscitation for traumatic hemorrhagic shock remains controversial since current protocols using large-volume crystalloid may exacerbate post-traumatic inflammation and organ dysfunction. Experimental data suggests that hypertonic saline/dextran (HSD, 7.5% NaCl in 6% dextran-70) exerts antiinflammatory and immunomodulatory effects, reduces multiorgan dysfunction and improves outcome. First trial examining the immunomodulatory properties of HSD in humans. Based on experimental findings, this study proposes to determine whether a single bolus of HSD might ... |
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| Tumor Vaccination With Cytokine-Loaded Microspheres |
SEP 2004 |
9 pages |
| Authors:
Nejat K. Egilmez; LOUISVILLE UNIV FOUNDATION INC KY
|
| A single intra-tumoral injection of IL-l2 + GM-CSF-encapsulated microspheres promoted the suppression of primary tumor growth, prevented the development of additional tumors and extended survival in the her2-neu transgenic FVB/neuN murine mammary tumor model. Induction of a long-lived, systemic, tumor-specific immune response was demonstrated in adoptive cell transfer studies, cytotoxic T-cell assays, in vivo lymphocyte subset depletion studies and analysis of serum anti-tumor antibody levels. Repeated treatment was more effective ... |
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| Medical Managment of the Acute Radiation Syndrome: Recommendations of the Strategic National Stockpile Radiation Working Group |
15 JUN 2004 |
20 pages |
| Authors:
Jamie K. Waselenka; Thomas J. MacVittie; William F. Blakely; Nicki Pesik; Albert L. Wiley; William E. Dickerson; Horace Tsu; Dennis L. Confer; Norman Coleman; Thomas Seed; ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD
|
| Physicians, hospitals, and other health care facilities will assume the responsibility for aiding individuals injured by a terrorist act involving radioactive material. Scenarios have been developed for such acts that include a range of exposures resulting in few to many casualties. This consensus document was developed by the Strategic National Stockpile Radiation Working Group to provide a framework for physicians in internal medicine and the medical subspecialties to evaluate and ... |
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| Naked DNA Immunization for Prevention of Prostate Cancer in a Dunning Rat Prostate Tumor Model |
JUN 2004 |
56 pages |
| Authors:
Milcho S. Mincheff; GEORGE WASHINGTON UNIV WASHINGTON DC
|
| During year two of the granting period, we continued to study the efficacy of raising cytotoxic human T cell responses against the auto- antigens PAP and PSA with genetically modified autologous dendritic cells, The ability of dendritic cells (DCs), genetically modified with one of two types of plasmid DNA vaccines to stimulate lymphocytes from normal human donors and to generate antigen-specific responses, is compared. The first type, also called "secreted" ... |
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| The Road to Tolerance: Renal Transplant Tolerance Induction in Nonhuman Primate Studies and Clinical Trials |
21 MAY 2004 |
14 pages |
| Authors:
Eric A. Elster; Douglas A. Hale; Roslyn B. Mannon; Linda C. Cendales; S. J. Swanson; Allan D. Kirk; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
|
| Organ transplantation has become a standard life-saving therapy for many causes of end stage organ failure. Although valuable, it remains hampered by the requirement for, and complications of, immunosuppression to prevent immune rejection of the transplanted organ. It is now clear that rejection can be avoided in some experimental systems without a requirement of immunosuppressive medication, and these experimental concepts are now making their way into the clinic in the ... |
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| Molecular Biology Basis for the Response of Poly (ADP-Ribose) Polymerase and NAD Metabolism to DNA Damage Caused by Mustard Alkylating Agents |
MAY 2004 |
25 pages |
| Authors:
Mark E. Smulson; GEORGETOWN UNIV WASHINGTON DC
|
| The mechanism of toxicity of sulfur mustard was investigated by examining the biochemical effects of the analog 2-chioroethylethyl sulfide (CEES) in both human Jurkat cells as well as normal human lymphocytes. Exposure of both cells to CEES resulted in a marked decrease in the intracellular concentration of the reduced form of glutathione ((3511), and CEES-induced cell death was potentiated by L-buthionine sulfoximine, an inhibitor of GSH synthesis. CEES increased the ... |
|
| Mutagen Sensitivity Apoptosis and Polymorphism in DNA Repairs as Measures of Prostate Cancer Risk |
FEB 2004 |
33 pages |
| Authors:
Radoslav Goldman; GEORGETOWN UNIV WASHINGTON DC
|
| This proposal evaluates interindividual differences in the response to genotoxic stress as prostate cancer risk factors. To this end we use measurements of mutagen sensitivity, apoptosis, comet assay, and single nucleotide polymorphisms in DNA repair genes OGG1 and XRCCl. These biomarkers are evaluated in 100 prostate cancer cases and 100 controls matched on age and race in order to measure response to bleomycin exposure is short-term cultured lymphocytes to define ... |
|
| Regulation of TRAIL-Mediated Apoptosis in Prostate Cancer by Overexpression in XIAP |
JAN 2004 |
43 pages |
| Authors:
Benjamin Bonavida; CALIFORNIA UNIV LOS ANGELES
|
| The failure to eradicate advanced prostate cancer that is resistant to conventional therapies, such as chemo and hormonal therapies, has led to the exploration of novel therapeutic applications such as immunotherapy. One form of immunotherapy is to generate anti-tumor cytotoxic lymphocytes that can recognize and eradicate resistant tumor cells. Cytotoxic lymphocytes mediate their killing by various mechanisms including the perforin granzyme pathway and by members of the TNF-alpha superfamily. Among ... |
|
| Compact High Power Repetitive Pulsed Power Instrumentation |
JAN 2004 |
6 pages |
| Authors:
Martin A. Gundersen; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| The vacuum system, pulse generator and oscilloscopes are used for pseudospark-BLT switch research. The pumping system is for achieving necessary high vacuum conditions. Observations of cell membrane perturbation in real time with sub-nanosecond time resolution is made possible by the PicoStar HR-12 CCD camera system and its custom table purchased under this AFOSR Grant. This High- Speed CCD camera system is a component of AFOSR-supported Transient Plasma Ignition research as ... |
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| Cross-Linking Interferes With Assessing Sulfur Mustard-Induced DNA Damage in Human Peripheral Blood Lymphocytes Using the Comet Assay |
2004 |
9 pages |
| Authors:
Janet Moser; Claire F. Levine; Delvena R. Thomas-Dunmeyer; William J. Smith; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| Sulfur mustard (SM) is a blistering agent that produces DNA strand breaks. To detect SM-induced DNA single strand breaks in human peripheral blood lymphocytes (PBL), cells were exposed to various concentrations of SM (10 to 1000 muM), and the comet assay (single-cell gel electrophoresis) was performed. We observed a SM concentration- and time-dependent increase in detectable DNA damage. To test whether SM-induced DNA cross-linking inhibits DNA migration in the comet ... |
|
| Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques |
DEC 2003 |
25 pages |
| Authors:
Thomas W. Geisbert; Lisa E. Hensley; Tom Larsen; Howard A. Young; Douglas S. Reed; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
| Ebola virus (EBOV) infection causes a severe and fatal hemorrhagic disease that in many ways appears to be similar in humans and nonhuman primates; however, little is known about the development of EBOV hemorrhagic fever. In the present study, 21 cynomolgus monkeys were experimentally infected with EBOV and examined sequentially over a 6-day period to investigate the pathological events of EBOV infection that lead to death. Importantly, dendritic cells in ... |
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| Radiation Induced Bystander Effects in Human Lymphoblastoid Cells |
DEC 2003 |
|
| Authors:
Tamika M. Segura; Diana Wilkinson; Louise Prud'honne-Lalonde; Erika M. Thorleifson; Sylvie Lachapelle; DEFENCE RESEARCH AND DEVELOPMENT CANADAOTTAWA (ONTARIO)
|
| It is well accepted that cells, in response to radiation, may release transmissible factors. These transmissible factors, clastogenic factors, have been reported to induce genomic instability in cells that have not been directly exposed to radiation. We hypothesize that this observed bystander effect might be a consequence of cellular interactions via secretory proteins released by the irradiated cells to affect the non-irradiated cells and initiate a systemic stress response to ... |
|
| Functional Analysis of LIM Domain Proteins and Co-Factors in Breast Cancer |
OCT 2003 |
38 pages |
| Authors:
Ning Wang; Bogi Andersen; CALIFORNIA UNIV IRVINE
|
| We identified a novel transcription factor, LMO-4, which exhibits prominent expression in epithelial cells, including that of the breast. Since previous members of the LIM only (LMO) gene family are oncogenes in lymphocytes, we hypothesized that LMO-4 may play a role in mammary gland development and cancer. We have created transgenic mice in which we overexpress a dominant negative LMO-4 under the MMTV promoter (MMTV-engrailed-LMO4) to test the role of ... |
|
| Epstein-Barr Virus and Breast Cancer |
SEP 2003 |
15 pages |
| Authors:
Wing C. Chan; NEBRASKA UNIV MEDICAL CENTER OMAHA
|
| Epstein Barr virus (EBV) has been implicated as a cofactor in several human malignancies. The possibility that EBV may play a role in the development of breast cancer has been raised in recent years. However, published reports have shown conflicting results. This could be related to the different as says employed and also possible geographical variations in the incidence of this infection. We collected 282 cases of invasive breast carcinomas, ... |
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| Development of Superagonist Mimics to Epitopes Defined by Cytotoxic and Helper T Cells |
AUG 2003 |
13 pages |
| Authors:
Malcolm S. Mitchell; WAYNE STATE UNIV DETROIT MI
|
| Human mucin glycoprotein MUC1 is a "self' peptide overexpressed on all surfaces of breast cancers and is an attractive candidate immunogen for a breast cancer vaccine. MUC1 is only weakly immunogenic, eliciting a low frequency of cytolytic T lymphocytes (CTL). We proposed to enhance immunity to MUC1 by using peptide mimics of native MUC1 epitopes. Mimic peptides contain amino acid substitutions; some mimics augment the T cell response to the ... |
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| Assessment of the Genotoxic Effects of High Peak-Power Pulsed Electromagnetic Fields (EMFs) |
10 JUL 2003 |
29 pages |
| Authors:
Nikolai Chemeris; RUSSIAN ACADEMY OF SCIENCES PUSHCHINO (RUSSIA)
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| This report results from a contract tasking Russian Academy of Sciences as follows: Because of the widespread increase in man-made sources of electromagnetic fields (EMFs), including high peak-power pulsed EMF (HPPP EMF), it has become important to study the health consequences, including possible genotoxic effects of such fields. Because of the simultaneous increase in other environmental toxins, it is difficult to isolate the effects of EMFs in natural human populations. ... |
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| Effect of Tumor-Derived TGF-Beta on the Efficacy of Dendritic Cell Vaccines |
JUL 2003 |
29 pages |
| Authors:
James J. Kobie; Emmanuel T. Akporiaye; ARIZONA UNIV TUCSON
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| As antigen presenting cells capable of inducing strong cytotoxic T lymphocyte (CTL) responses to specific antigens, dendritic cells (DCs) have become prime candidates for use in cancer immunotherapy. It has been shown that treatment of DCs with tumor cell supermatants results in reduced expression of MHC class II and reduced ability to induce a CTb response. These findings have led to the suggestion that tumors secrete soluble factors that inhibit ... |
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