| Fractional Analysis of Escherichia coli O157:H7 by Mass Spectrometry-Based Proteomics |
Oct 2012 |
22 pages |
| Authors:
Vicky L Bevilacqua; Rabih E Jabbour; Mary M Wade; Samir V Deshpande; Patrick E McCubbin; ARMY EDGEWOOD CHEMICAL BIOLOGICAL CENTER APG MD
|
 | This report is required for the U.S. Army Edgewood Chemical Biological Center In-House Laboratory Independent Research project Membrane Vesicles and Extracellular Proteins in Antibiotic Resistance and Virulence . Certain extracellular proteins of pathogenic bacteria have been shown to function in survival mechanisms such as host immune system modulation (Vranakis, et al., July 27, 2011, J. Proteome Res. DOI 10.1021/pr200422f) and biofilm formation (Ostrowski, A., et al., 2011, J. Bacteriol. 193:4043). ... |
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| Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer |
Oct 2012 |
15 pages |
| Authors:
Peter P Lee; CITY OF HOPE BECKMAN RESEARCH INST DUARTE CA
|
 | Over the first 6 months of this award, we have focused on building a strong team, clinical collaborations, patient enrollment and samples acquisition. Our team has tested and optimized a number of protocols to process samples, generate antigen- presenting cells, and expand T cells for testing against tumor lysates from the Spellman group. This process is nearly complete, and we are positioned to work through the entire process as outlined ... |
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| Enhancing the Breadth of Efficacy of Therapeutic Vaccines for Breast Cancer |
Oct 2012 |
12 pages |
| Authors:
Jill E Slansky; John Kappler; Tullia Bruno; Daniel Munson; Taizo Nakano; COLORADO UNIV AURORA CO
|
 | During the current funding period, we have started a collaborative effort between the laboratories of Peter Lee at City of Hope National Medical Center, Paul Spellman at Oregon Health Sciences University, and Jill Slansky at University of Colorado Anschutz Medical Campus. Our multi-team project is aimed at enhancing the function of pre-existing antitumor T cells from breast cancer patients. In the first year, we have focused on generating reagents and ... |
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| Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer |
Oct 2012 |
11 pages |
| Authors:
Paul Spellman; Dmitri Rosanov; Kami Chiotti; OREGON HEALTH AND SCIENCES UNIV PORTLAND
|
 | The focus of the Spellman/Gray work group over the past year has been upon the generation of materials, tools, and data for the purpose of aiding and supporting the research and findings of the entire multi-team collaboration endeavoring to identify antigenic targets of breast cancer-infiltrating T cells. During this time, our group generated the breast cancer cell line lysates necessary to provide uniform sources of major antigens associated with each ... |
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| Systemic and Local Vaccination against Breast Cancer with Minimum Autoimmune Sequelae |
Oct 2012 |
5 pages |
| Authors:
Wei-Zen Wei; WAYNE STATE UNIV DETROIT MI
|
 | Our goal is to eliminate the tumor by vaccination and local ablation to render long-term immune protection without excessive autoimmune sequelae. Complimenting this regimen is systemic modulation of natural/induced Treg (iTreg) and intratumoral expression of immune augumenting cytokines. The two aims are to (1) Test the hypothesis that cryosurgery of cytokine enriched tumors amplifies Her-2 vaccine response, and (2) Test the hypothesis that disabling iTreg conversion enhances Her-2 immunity, not ... |
|
| Hearing Restoration in Mouse Models with Noise-induced Hearing Loss |
27 Sep 2012 |
10 pages |
| Authors:
Jian Zuo; SAINT JUDE CHILDREN'S RESEARCH HOSPITAL MEMPHIS TN
|
 | To characterize the regenerative capacity of SCs in mice after noise-induced damage and transient or permanent inactivation of p161nk4a and assess the ability of Atoh1 to transdifferentiate SCs into HCs after noise-induced damage in mice. |
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| Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy |
01 Sep 2012 |
5 pages |
| Authors:
Lee M Krug; SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
|
 | The Wilms' tumor gene, WT1, encodes transcription factors that regulate cell proliferation, differentiation, and apoptosis. WT1 protein is highly expressed in malignant pleural mesothelioma (MPM), and is a rational target for immunotherapy. We have developed a vaccine comprised of four WT1 heteroclitic peptides that are given together with Montanide and GM-CSF as immunologic adjuvants. This WT1 vaccine was previously tested in a small pilot trial, and shown to be safe ... |
|
| Motor Cortex Stimulation Reverses Maladaptive Plasticity Following Spinal Cord Injury |
Sep 2012 |
20 pages |
| Authors:
Radi Masri; MARYLAND UNIV BALTIMORE
|
 | The majority of patients with spinal cord injury (SCI) develop intractable chronic neuropathic pain that is resistant to conventional pharmacologic treatments. An alternative and potentially effective modality of treatment motor cortex stimulation (MCS) offers hope for these patients. The purpose of this application is to elucidate the neurobiological basis of reduced pain following MCS. We propose that MCS reverses hyperalgesia by enhancing the activity in the GABAergic nucleus zona incerta ... |
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| Role of the Rb and p53 Tumor Suppressor Pathways in Mammary Tumorigenesis |
Sep 2012 |
21 pages |
| Authors:
Robert A Jones; UNIVERSITY HEALTH NETWORK TORONTO (ONTARIO)
|
 | Understanding the genetic pathways that contribute to the development of specific breast cancer subtypes will lead to the discovery of more effective therapies. Two of the most common genetic alterations in human cancers involve inactivation of the Rb and p53 tumor suppressor pathways. To directly investigate the role of these pathways in breast cancer, we generated mice with conditional deletion of Rb and p53 in the mammary epithelium. Combined loss ... |
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| Understanding and Managing Propagation on Large Networks - Theory, Algorithms, and Models |
Sep 2012 |
233 pages |
| Authors:
B A Prakash; CARNEGIE-MELLON UNIV PITTSBURGH PA DEPT OF COMPUTER SCIENCE
|
 | How do contagions spread in population networks? What happens if the networks change with time? Which hospitals should we give vaccines to, for maximum effect? How to detect sources of rumors on Twitter/Facebook? These questions and many others such as which group should we market to, for maximizing product penetration, how quickly news travels in online media and how the relative frequencies of competing tasks evolve are all related to ... |
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| Prospects for a Novel Ultrashort Pulsed Laser Technology for Pathogen Inactivation |
06 Jul 2012 |
27 pages |
| Authors:
Shaw-Wei D Tsen; Tzyy C Wu; Juliann G Kiang; Kong-Thon Tsen; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF MEDICINE
|
 | The threat of emerging pathogens and microbial drug resistance has spurred tremendous efforts to develop new and more effective antimicrobial strategies. Recently, a novel ultrashort pulsed (USP) laser technology has been developed that enables efficient and chemical-free inactivation of a wide spectrum of viral and bacterial pathogens. Such a technology circumvents the need to introduce potentially toxic chemicals and could permit safe and environmentally friendly pathogen reduction, with a multitude ... |
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| Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metatastic Breast Cancer |
Jul 2012 |
7 pages |
| Authors:
Donald Kufe; Baldev Vasir; David Avigan; DANA-FARBER CANCER INST BOSTON MA
|
 | The main objective of the study is to determine the safety, immunologic response, and clinical effect of vaccination with dendritic cell (DC)/breast cancer fusions administered in conjunction with IL-12 to patients with metastatic breast cancer. DC/breast carcinoma fusion cells present a broad array of tumor-associated antigens in the context of DC-mediated costimulation. In clinical studies, vaccination with fusion cells was well tolerated, induced immunologic responses in a majority of patients, ... |
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| Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy |
Jul 2012 |
12 pages |
| Authors:
David J Chung; SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
|
 | The purpose of this project is to study the immunomodulatory effect of Listeria on human dendritic cells (DCs) to optimize Listeria-based DC cancer vaccines. The project aims are: 1) Compare the activation and maturation of different human DC subsets in response to Listeria infection. 2) Define the induction of CD4+/CD8+ T-cell and NK cell responses to Listeriaactivated DCs presenting a melanoma tumor-associated antigen. 3) Augment the immunogenicity of Listeria-activated DCs ... |
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| Vaccine Immunotherapy for Prostate Cancer |
May 2012 |
12 pages |
| Authors:
David Lubaroff; IOWA UNIV IOWA CITY
|
 | The purpose of the research supported by this award is to conduct a Phase II clinical trial (study) of an adenovirus/PSA (Ad/PSA) vaccine for the treatment of prostate cancer. Two protocols have been used in the trial: #1 - Phase II study of Adenovirus/PSA vaccine in men with recurrent prostate cancer after local therapy; and #2 - Phase II study of Adenovirus/PSA vaccine in men with hormone refractory prostate cancer. ... |
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| Second-Generation Therapeutic DNA Lymphoma Vaccines |
May 2012 |
7 pages |
| Authors:
Larry W Kwak; M D ANDERSON CANCER CENTER HOUSTON TX
|
 | Lenalidomide is an effective therapeutic agent with direct inhibitory effects on malignant B- and plasma cells and immunomodulatory effects on the T cell activation. The dual function of lenalidomide makes it an appealing candidate for combination with other novel agents for lymphoma and myeloma therapy. In this study, we investigated the immune stimulatory effects of lenalidomide, administrated to mice in doses which provided comparable pharmacokinetics to human patients, on the ... |
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| Quadrivalent Human Papillomavirus Vaccine Initiation, Coverage, and Compliance Among U.S. Active Component Service Women, 2006-2011 |
May 2012 |
2 pages |
| Authors:
Hala Maktabi; Sharon L Ludwig; Angelia Eick-Cost; Uma D Yerubandi; Joel G Gaydos; ARMED FORCES HEALTH SURVEILLANCE CENTER SILVER SPRING MD
|
 | Human papillomavirus (HPV)is the most common sexually transmitted pathogen detected among U.S. service members. An estimated 169,682 incident diagnoses of HPV infection occurred between 2004-2009 among active component U.S. service members (rate of 2,306 cases per 100,000 person years). In 2006, a 3-dose HPV quadrivalent vaccine (HPV4), which protects against common HPV strains (types 6, 11, 16, 18) responsible for about 70 percent of cervical cancers and 80 percent of ... |
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| Vaccination with Dendritic Cell Myeloma Fusions in Conjunction with Stem Cell Transplantation and PD-1 Blockade |
May 2012 |
11 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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| The Role of Natural Killer (NK) Cells and NK Cell Receptor Polymorphisms in the Assessment of HIV-1 Neutralization |
11 Apr 2012 |
12 pages |
| Authors:
Bruce K Brown; Lindsay Wieczorek; Gustavo Kijak; Kara Lombardi; Jeffrey Currier; Maggie Wesberry; John C Kappes; Viseth Ngauy; Mary Marovich; Nelson Michael; WALTER REED ARMY INST OF RESEARCH ROCKVILLE MD US MILITARY HIV RESEARCH PROGRAM/DIVISION OF RETROVIROLOGY
|
 | The importance of innate immune cells in HIV-1 pathogenesis and protection has been highlighted by the role of natural killer (NK) cells in the containment of viral replication. Use of peripheral blood mononuclear cells (PBMC) in immunologic studies provides both HIV-1 target cells (ie. CD4+ T cells), as well as anti-HIV-1 effector cells, such as NK cells. In this study, NK and other immune cell populations were analyzed in HIV-negative ... |
|
| Medical Surveillance Monthly Report (MSMR). Volume 19, Number 3, March 2012 |
Mar 2012 |
25 pages |
| Authors:
ARMED FORCES HEALTH SURVEILLANCE CENTER SILVER SPRING MD
|
 | After a 12-year hiatus, military recruit training centers resumed administration of adenovirus type 4 and type 7 vaccine, live, oral (adenovirus vaccine) to trainees beginning in October of 2011. Subsequently, rates of febrile respiratory illnesses (FRI) and adenovirus isolations markedly declined. These findings are consistent with those of a placebo-controlled efficacy trial conducted prior to the vaccine s licensure by the U.S. Food and Drug Administration. Continued surveillance will clarify ... |
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| Sensitivity of Breast Cancer Stem Cells to TRA-8 Anti-DR5 Monoclonal Antibody |
Feb 2012 |
33 pages |
| Authors:
Angelina L Joshi; ALABAMA UNIV IN BIRMINGHAM
|
 | Basal-Like Breast Cancer (BLBC) accounts for 13% of all breast carcinomas (1). It is characterized by a unique mRNA profile with CK5/6 expression, inactivation of BRCA1 and lack of estrogen receptor and HER-2 amplification (1-3). BLBC is considered one of the most aggressive, metastatic, and chemoresistant breast cancer subtypes (4). Its poor prognosis is linked to enrichment for tumor initiating cancer stem cells (CSC) (5). The Cancer Stem Cell Model ... |
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| Effects of Relative Humidity and Spraying Medium on Ultraviolet (UV) Decontamination of Filters Loaded with Viral Aerosols |
Feb 2012 |
9 pages |
| Authors:
Myung-Heui Woo; Tammy Smith; Chang-Yu Wu; Adam Grippin; Diandra Anwar; Joseph D Wander; FLORIDA UNIV GAINESVILLE DEPT OF ENVIRONMENTAL ENGINEERING SCIENCES
|
 | Although respirators and filters are designed to prevent the spread of pathogenic aerosols, a stockpile shortage is anticipated during the next flu pandemic. Contact transfer and reaerosolization of collected microbes from used respirators are also a concern. An option to address these potential problems is ultraviolet (UV) irradiation, which inactivates microbes by dimerizing thymine in nucleic acids. The objective of this study was to determine the effects of transmission mode ... |
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| Microwave-Irradiation-Assisted HVAC Filtration for Inactivation of Viral Aerosols (Postprint) |
Feb 2012 |
11 pages |
| Authors:
Myung-Heui Woo; Chang-Yu Wu; Adam Grippin; Joseph D Wander; FLORIDA UNIV GAINESVILLE DEPT OF ENVIRONMENTAL ENGINEERING SCIENCES
|
 | Viral aerosols collected on a filter medium can reaerosolize and the filter can serve as a fomite. This study evaluated the inactivation efficiency (IE) achieved by filtration coupled with microwave irradiation. To test in-flight microwave decontamination, microwave irradiation was applied to coupons cut from a ventilation filter and supported on a SiC disk during three cycles of selected irradiation times (1, 2.5, 5, and 10 min) per 10 min of ... |
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| The Need For Continued Development Of Ricin Countermeasures |
Jan 2012 |
5 pages |
| Authors:
Ronald B Reisler; Leonard A Smith; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
 | Ricin toxin, an extremely potent and heat-stable toxin produced from the bean of the ubiquitous Ricinus communis (castor bean plant), has been categorized by the US Centers for Disease Control and Prevention (CDC) as a category B biothreat agent that is moderately easy to disseminate. Ricin has the potential to be used as an agent of biological warfare and bioterrorism. Therefore,there is a critical need for continued development of ricin ... |
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| Breast Cancer Vaccines that Overcome Tolerance and Immune Suppression |
Jan 2012 |
14 pages |
| Authors:
Olesya Chornoguz; MARYLAND UNIV BALTIMORE
|
 | Our previous studies indicated that Ii- vaccines are more efficient in CD4+ T-cell activation than Ii+ cells, and that mouse MHC II vaccines caused regression of established tumors in mice. In vitro studies with human MHC II vaccines demonstrated that the Iivaccines activated a population of CD4+ T-cells that is distinct from the population activated by Ii+ cells. This observation is consistent with our hypothesis that the absence of Ii ... |
|
| The Relevance of Rabies to Today's Military |
Jan 2012 |
9 pages |
| Authors:
Edwin D Cooper; Mustapha Debboun; ARMY MEDICAL DEPT CENTER AND SCHOOL FORT SAM HOUSTON TX
|
 | A 24-year-old Army Specialist was assigned as a cook at Combat Base Chamkani, Paktia Province, Afghanistan, from May 2010 to May 2011. He was a known animal enthusiast and had been caring for unauthorized dogs in his unit's area, in spite of General Order Number 1 which forbade the keeping of animals in theater. Feral dogs have been a perennial issue throughout the combat theaters of Iraq and Afghanistan, as ... |
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| Adenovirus-5-Vectored P. falciparum Vaccine Expressing CSP and AMA1. Part B: Safety, Immunogenicity and Protective Efficacy of the CSP Component |
Oct 2011 |
22 pages |
| Authors:
Cindy Tamminga; Martha Sedegah; David Regis; Ilin Chuang; Judith E Epstein; Michele Spring; Jose Mendoza-Silveiras; Shannon McGrath; Santina Maiolatesi; Sharina Reyes; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD MALARIA PROGRAM
|
 | A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge. NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one ... |
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| Progression of Pathogenic Events in Cynomolgus Macaques Infected with Variola Virus |
Oct 2011 |
14 pages |
| Authors:
Victoria Wahl-Jensen; Jennifer A Cann; Kathleen H Rubins; John W Huggins; Robert W Fisher; Anthony J Johnson; Fabian de Kok-Mercado; Thomas Larsen; Jo L Raymond; Lisa E Hensley; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
 | Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models ... |
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| Priming the Tumor Immune Microenvironment Improves Immune Surveillance of Cancer Stem Cells and Prevents Cancer Recurrence |
Oct 2011 |
13 pages |
| Authors:
Ralph R Reisfeld; Debbie Liao; Yunping Luo; SCRIPPS RESEARCH INST LA JOLLA CA
|
 | We were able to complete Specific Aim #1 of our two-aim application by extending our preliminary data. Thus, we demonstrated that our targeted elimination of cancer associated fibroblasts (CAFs) with a pFap vaccine in combination with doxorubicin (Dox) chemotherapy can prevent tumor-induced immune suppression. This, in turn, enhanced endogenous anti- tumor immunity, resulting in suppression of spontaneous metastasis and increased life span. Our findings re-emphasize the important contribution of CAFs ... |
|
| Optimization of Assays to Assess Dendritic Cell Activation and/or Energy in Ebola Infection |
Oct 2011 |
9 pages |
| Authors:
Christopher F Basler; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
 | The immune responses during lethal virus infection and the correlates of protective immunity in vaccinated macaques are not well understood. This study aims to develop assays that can predict protection with the various vaccine platforms designed to provide immunity to filovirus (Ebolavirus (EBOV) and Marburgvirus (MARV)) infection. A secondary aim is to better understand the aspects of virus on the immune response in animals that receive no intervention. As part ... |
|
| Systemic And Local Vaccination Against Breast Cancer With Minimum Autoimmune Sequelae |
Oct 2011 |
5 pages |
| Authors:
Wei-Zen Wei; WAYNE STATE UNIV DETROIT MI
|
 | Our goal is to eliminate the tumor by vaccination and local ablation to render long-term immune protection without excessive autoimmune sequelae. Complimenting this regimen is systemic modulation of natural/induced Treg (iTreg) and intratumoral expression of immune augumenting cytokines. The two aims are to (1) Test the hypothesis that cryosurgery of cytokine enriched tumors amplifies Her-2 vaccine response, and (2) Test the hypothesis that disabling iTreg conversion enhances Her-2 immunity, not ... |
|
| N-Acetyltransferase 1 Polymorphism and Breast Cancer Risk |
Oct 2011 |
127 pages |
| Authors:
Lori Millner; LOUISVILLE UNIV KY
|
 | activation or inactivation. NAT1*10 and NAT1*14, common variant alleles have been associated with increased risk for numerous cancers including breast. NAT1 is also upregulated in breast cancer. We employed a novel approach to study functional differences caused by NAT1*10 and NAT1*14 polymorphisms by using constructs that mimic complete human mRNAs by including the 5 -UTR, coding region and 3 -UTR. Significantly more enzymatic activity, protein expression, mRNA levels and 4-aminobiphenyl-induced ... |
|
| Vaccine Development for Biothreat Alpha Viruses |
25 Sep 2011 |
10 pages |
| Authors:
Kevin B Spurgers; Pamela J Glass; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
|
 | The majority of alpha virus is non-pathogenic to humans. However, select alpha viruses can cause severe disease in humans during the course of naturally occurring epizootic outbreaks, or accidental infection of laboratory personnel. Natural infections occur through the bite of an infected mosquito. However, pathogenic alpha viruses, including Venezuelan, eastern, and western equine encephalitis viruses, have proven to be highly infectious via the aerosol route. Given this aerosol infectivity, ease ... |
|
| Immunotherapeutic Strategies in Breast Cancer: Preclinical and Clinical Trials |
Sep 2011 |
13 pages |
| Authors:
Sandra J Gendler; MAYO CLINIC SCOTTSDALE AZ
|
 | This project is focused on novel tumor vaccines directed at MUC1 and other tumor antigens. Our specific aims are: 1) To assess the effectiveness of vaccines against MUC1 and other tumor antigens in the prevention and treatment of spontaneous breast carcinomas in mice; 2) To translate an effective vaccine strategy into a phase I clinical trial in patients with undetectable disease following standard therapy. The model of spontaneous mammary cancer ... |
|
| 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 ... |
|
| Randomized Phase 2 Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy |
Sep 2011 |
6 pages |
| Authors:
Lee M Krug; MEMORIAL SLOAN-KETTERING CANCER CENTER NEW YORK
|
 | The Wilms' tumor gene, WT1, encodes transcription factors that regulate cell proliferation, differentiation, and apoptosis. WT1 protein is highly expressed in malignant pleural mesothelioma (MPM), and is a rational target for immunotherapy. We have developed a vaccine comprised of four WT1 heteroclitic peptides that are given together with Montanide and GM-CSF as immunologic adjuvants. This WT1 vaccine was previously tested in a small pilot trial, and shown to be safe ... |
|
| TPD52: A Novel Vaccine Target for Prostate Cancer |
Sep 2011 |
20 pages |
| Authors:
Robert Bright; TEXAS TECH UNIV HEALTH SCIENCES CENTER LUBBOCK
|
 | Tumor protein D52 (D52) is a novel self-onco-antigen involved in cellular transformation, proliferation and metastasis that is over-expressed in prostate cancer cells. The overall goal of this Award is to test the efficacy of D52-based vaccines in the TRAMP murine model of prostate cancer, and to characterize vaccine induced mechanisms of tumor immunity. Due to unforeseen circumstances during this funding period primarily involving the animal vendor and maternity leave for ... |
|
| Development Of A Vaccine Targeting Triple-Negative Breast Cancer |
Sep 2011 |
9 pages |
| Authors:
Denise Cecil; SEATTLE UNIV WA
|
 | The insulin-like growth factor (IGF) pathway plays an important role in breast cancer growth and metastasis. The IGF-I receptor (IGF-IR) is over-expressed in almost 50% of triple negative breast cancers (TNBC). Thus, therapeutically targeting tumor cells which have upregulated IGF-IR may be a promising approach to treat TNBC. IGF-IR is immunogenic in breast cancer and is a potential target for active immunization. We sought to develop a vaccine that will ... |
|
| Tulane/Xavier Vaccine Development/Engineering Project |
Aug 2011 |
8 pages |
| Authors:
John D Clements; Lucy Freytag; Vijay John; Tarun Mandal; TULANE UNIV NEW ORLEANS LA SCHOOL OF MEDICINE
|
 | The Tulane/Xavier Biodefense Vaccine Development/Engineering project will develop new vaccines against biological threat agents to aid the war-fighter. Through the innovative use of nanotechnology, researchers and engineers from the Tulane University Schools of Medicine and Science & Engineering and the Xavier College of Pharmacy will fabricate nanoparticulate systems that are effective for transdermal and mucosal delivery of life-saving vaccines. One aim of this project will be to compare different nanocarriers ... |
|
| Fusion of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metastatic Breast Cancer. Addendum |
Aug 2011 |
6 pages |
| Authors:
Donald W Kufe; DANA-FARBER CANCER INST BOSTON MA
|
 | The main objective of the study is to vaccinate patients with metastatic breast cancer with a viable dendritic cell (DC)/breast cancer fusions in conjuction with IL-12 to induce an immunological response with the hope that this combination would further enhance vaccine response by promoting Th1 cytokine induction and T cell activation. In this approach, the entire repertoire of tumor antigens, including those yet to be identified, are expressed with the ... |
|
| Hic-5's Regulatory Role in TGFB Signaling In Prostate Stroma |
Jul 2011 |
15 pages |
| Authors:
Melanie Grubisha; PITTSBURGH UNIV PA
|
 | In this study, we attempt to demonstrate that a reactive stroma maintains the ability to restrain cancer cell motility, but this inhibition is lost when local TGF production stimulates an increased production of stromal ROS that in turn inactivates the inhibitor. We show that in the absence of TGF , a myofibroblastic prostate stromal cell (WPMY 1) produces a motility inhibitory factor that limits motility in a highly aggressive PCa ... |
|
| Genotype Diversity and Distribution of Orientia tsutsugamushi Causing Scrub Typhus in Thailand |
Jul 2011 |
7 pages |
| Authors:
Toon Ruang-areerate; Pimmada Jeamwattanalert; Wuttikorn Rodkvamtook; Allen L Richards; Piyanate Sunyakumthorn; Jariyanart Gaywee; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
|
 | Scrub typhus, caused by antigenically disparate isolates of Orientia tsutsugamushi, is a widely distributed mite-borne human disease in the Asia Pacific region. Information regarding the heterogeneity of the immunodominant 56-kDa type-specific antigen (TSA) gene is crucial for the design and evaluation of scrub typhusspecific diagnostic assays and vaccines. Using indirect immunofluorescence assays (IFA) and PCR assays, 0.tsutsugamushi was detected samples from rodents and patients with fever of unknown origin obtained ... |
|
| Enhancing the Efficacy of Prostate Cancer Immunotherapy by Manipulating T-Cell Receptor Signaling in Order to Alter Peripheral Regulatory T-Cell Activity |
Jul 2011 |
20 pages |
| Authors:
Andrew Gray; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
 | Immunotherapeutic strategies are a novel treatment option for incurable late-stage and metastatic prostate cancer. Several prostate-related antigens have been identified and even used clinically in therapeutic vaccine strategies, but the results have been disappointing. The activity of CD4+CD25+FOXP3+ regulatory T cells (Tregs) is a mechanism of peripheral tolerance that regulates immune responses, including those induced by therapeutic vaccination against cancer-associated antigens. PEST-domain enriched tyrosine phosphatase (PEP) is a critical negative ... |
|
| A 2011 Risk/Benefit Analysis of the Anthrax Vaccine Immunization Program |
10 Jun 2011 |
97 pages |
| Authors:
Karla L Davis; ARMY COMMAND AND GENERAL STAFF COLL FORT LEAVENWORTH KS
|
 | Safety, efficacy, and legal concerns surrounded the Department of Defense (DoD) Anthrax Vaccine Immunization Program (AVIP) in the early and mid-2000s. Production capacity, patient refusals, and legal injunctions limited vaccine delivery during this time period. Since 2007, the Anthrax Vaccine Adsorbed (AVA) has been administered to all service members deploying to high-risk areas except those medically or administratively exempt. This thesis evaluates the current AVIP in terms of associated risks ... |
|
| Enhancing Therapeutic Cellular Prostate Cancer Vaccines |
JUN 2011 |
40 pages |
| Authors:
Christian Gomez; MAYO CLINIC ROCHESTER MN
|
 | Prostate cancer (CaP) is characterized by unique prostate-associated antigens; hence, it has been considered a prime candidate for immunotherapy. Despite numerous laboratory advances, clinical outcomes have been partial and transient. The overall goal of the proposed studies is to optimize the effectiveness of therapeutic whole-cell CaP vaccines by taking into consideration tumor-associated hypoxia as a relevant determinant of tumor antigenicity. Transcriptome studies revealed that gene expression in hypoxically cultured cells ... |
|
| Invariant NKT Cell Ligands for Prostate Cancer Vaccines |
Jun 2011 |
9 pages |
| Authors:
Steven P Balk; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
 | Invariant natural killer T cells (iNKT cells), through their ability to mature dendritic cells (DCs) and provide help for CD4 and CD8 T cell responses, can play a major role in regulation of the cellular adaptive immune response. Our major objective in this proposal is to identify an optimal agent and method of delivery for iNKT cell activation and enhancement of cytolytic T cell responses against prostate/PCa associated antigens. Our ... |
|
| SLC5A8-Mediated Switching of STAT3 from a Pro-Oncogenic Signal into a Pro-Apoptotic Signal in Breast Cancer |
Jun 2011 |
56 pages |
| Authors:
Muthusamy Thangaraju; MEDICAL COLL OF GEORGIA AUGUSTA RESEARCH INST
|
 | Overall our findings demonstrated that the novel tumor suppressor SLC5A8 is necessary to mediate the pro-apoptotic function of STAT3 in the normal mammary epithelial cells. To support our findings, we observed that the functional inactivation of SLC5A8 is associated with mammary gland involution delay, hyperplasia, and early onset of mammary tumorigenesis as well as accelerated lung metastasis. SLC5A8 associated tumor suppression is mainly linked to its effects of transporting the ... |
|
| Cancer and Stroma-Targeted Immunotherapy with a Genetically Modified DC Vaccine |
01 MAY 2011 |
14 pages |
| Authors:
Xiao-Tong Song; BAYLOR COLL OF MEDICINE HOUSTON TX
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 | While current DC vaccines are safe, their antitumor activity is limited. This is foremost due to the presence of regulatory T cells (Tregs), which create an immunosuppressive environment in breast cancer patients. In addition, there is increasing evidence that effective solid tumor vaccines have to target cancer cells as well as their supporting stroma. Thus, overcoming Treg mediated immune suppression and targeting the tumor stroma in addition to breast cancer ... |
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| Second-Generation Therapeutic DNA Lymphoma Vaccines |
MAY 2011 |
14 pages |
| Authors:
Larry Kwak; M D ANDERSON CANCER CENTER HOUSTON TX
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 | The idea of genetic vaccination originated from the observation that injection of DNA into living animals resulted in expression of gene products in vivo. Preclinical studies revealed that genetic immunization induced both antigen-specific antibody and cytotoxic T lymphocyte. Early human trials of DNA vaccines have been mainly focused on infectious disease, and vaccines against malignant disease have activated anti-tumor immunity in cancer patients and extended remission. Compared with proteins or ... |
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| Functional Interaction between Rb and Thoc1 in Mouse Prostate Tumorigenesis |
MAY 2011 |
8 pages |
| Authors:
Meenalakshmi Chinnam; HEALTH RESEARCH INC BUFFALO NY
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 | A large percentage of prostate cancers show either loss or mutational inactivation of the Rb tumor suppressor gene. Rb mediates its tumor suppressor function through its association with other cellular proteins. Our study focuses on Thoc 1 protein, which interacts with the N terminal region of Rb protein and therby may mediate some Rb functions. Previous reports show that Thoc1 is unregulated in some cancer types and is required for ... |
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| Vaccine Immunotherapy for Prostate Cancer |
May 2011 |
10 pages |
| Authors:
David M Lubaroff; IOWA UNIV IOWA CITY
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 | The purpose of the research supported by this award is to conduct a Phase II clinical trial (study) of an adenovirus/PSA (Ad/PSA) vaccine for the treatment of prostate cancer. Two protocols have been used in the trial: #1 - Phase II study of Adenovirus/PSA vaccine in men with recurrent prostate cancer after local therapy; and #2 - Phase II study of Adenovirus/PSA vaccine in men with hormone refractory prostate cancer. ... |
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