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Tdiscovery And Development Of Novel Therapeutic Agents For Advanced Melanoma, Zhao Wang 2010 University of Tennessee Health Science Center

Tdiscovery And Development Of Novel Therapeutic Agents For Advanced Melanoma, Zhao Wang

Theses and Dissertations (ETD)

Malignant melanoma is the most dangerous form of skin cancer and accounts for about 75% of skin cancer deaths. Once diagnosed at the metastatic stage, it has a very poor prognosis with a median survival rate of 6 months and a 5-year survival rate of less than 5%. In addition, melanoma has become an important public health hazard owing to its rising incidence, which has been well documented over the past 50 years. Currently there is no effective way to treat melanoma. It is highly resistant to existing chemotherapy, radiotherapy, and immunotherapy. Over the past 30 years, only two drugs ...


Ns1 Of H5n1 Interacts With Sap-97 In A Pdz-Dependent Manner To Disrupt Epithelial Barrier Integrity, Veronica Garcia Conoley 2010 University of Tennessee Health Science Center

Ns1 Of H5n1 Interacts With Sap-97 In A Pdz-Dependent Manner To Disrupt Epithelial Barrier Integrity, Veronica Garcia Conoley

Theses and Dissertations (ETD)

The ability of influenza A virus to cause global pandemics has been a great concern throughout history and poses a serious health risk worldwide. Pandemic outbreaks throughout history, such as the Spanish flu of 1918, have claimed the lives of millions of people worldwide. The current outbreak of avian influenza (H5N1) that began in 1997 is still claiming lives, and therefore efforts to understand the mechanisms of pathogenesis in this highly virulent virus are of the utmost importance. According to the World Health Organization, there have been 447 reported H5N1 human cases, resulting in 263 deaths. The pathology of H5N1 ...


Mechanism-Based Strategies To Enhance The Actions Of A, fabiola c. gomez 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Mechanism-Based Strategies To Enhance The Actions Of A, Fabiola C. Gomez

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Heat shock protein 90 (HSP90) is an abundant molecular chaperone that regulates the functional stability of client oncoproteins, such as STAT3, Raf-1 and Akt, which play a role in the survival of malignant cells. The chaperone function of HSP90 is driven by the binding and hydrolysis of ATP. The geldanamycin analog, 17-AAG, binds to the ATP pocket of HSP90 leading to the degradation of client proteins. However, treatment with 17-AAG results in the elevation of the levels of antiapoptotic proteins HSP70 and HSP27, which may lead to cell death resistance. The increase in HSP70 and HSP27 protein levels is due ...


Characterization And Optimization Of Antigen-Specific T Cell Responses During Ex Vivo Expansion Of Melanoma Tumor-Infiltrating Lymphocytes, yufeng li 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Characterization And Optimization Of Antigen-Specific T Cell Responses During Ex Vivo Expansion Of Melanoma Tumor-Infiltrating Lymphocytes, Yufeng Li

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Treatment of metastatic melanoma with tumor reactive T cells (adoptive T cell therapy, ACT) is a promising approach associated with a high clinical response rate. However, further optimization of this treatment modality is required to increase the clinical response after this therapy. ACT in melanoma involves an initial phase (pre-REP) of tumor-infiltrating lymphocyte (TIL) expansion ex vivo from tumor isolates followed by a second phase, “rapid expansion protocol” (REP) generating the billions of cells used as the TIL infusion product. The main question addressed in this thesis was how the currently used REP affected the responsiveness of the CD8+ T ...


An Assessment Of Obesity And Hyperphagia In Individuals With Smith-Magenis Syndrome, Carrie A. Crain 2010 University of Texas Graduate School of Biomedical Sciences at Houston

An Assessment Of Obesity And Hyperphagia In Individuals With Smith-Magenis Syndrome, Carrie A. Crain

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Smith-Magenis syndrome (SMS;OMIM# 182290) is a multiple congenital anomalies and mental retardation syndrome caused by a 3.7- Mb deletion on chromosome 17p11.2 or a mutation in the RAI1 gene. Although the majority of the SMS phenotype has been well described, limited studies are available describing growth patterns in SMS. There is some evidence that individuals with SMS develop obesity. Thus, this study aims to characterize the growth and potential influence of hyperphagia in a cohort of individuals with SMS. A retrospective chart review was conducted of 78 individuals with SMS through Baylor College of Medicine (BCM) at ...


First Trimester Screening And Its Impact On Uptake Of Diagnostic Testing, Deanna Darnes 2010 University of Texas Graduate School of Biomedical Sciences at Houston

First Trimester Screening And Its Impact On Uptake Of Diagnostic Testing, Deanna Darnes

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Introduction: First Trimester Screening (FTS) combines maternal age with fetal nuchal translucency (NT) and maternal analytes to identify pregnancies at an increased risk for Down syndrome and trisomy 18. Though the accuracy of this screening is high, it cannot replace the conclusive accuracy of prenatal diagnostic testing (PDT). Since FTS has been available, a decrease in the number of women who pursue PDT has been observed. This study sought to determine if there has been a significant change in the amount of PDT performed in our clinics, if the type of FTS result affects the patient’s decision regarding PDT ...


Pregnancy Outcomes With Exposure To The Mycophenolic Acid Products (Mpa), To Dung K. Nguyen, Faith Carlin, Lisa A. Coscia, Dawn Armenti, Vincent T. Armenti 2010 Thomas Jefferson University

Pregnancy Outcomes With Exposure To The Mycophenolic Acid Products (Mpa), To Dung K. Nguyen, Faith Carlin, Lisa A. Coscia, Dawn Armenti, Vincent T. Armenti

Department of Surgery Faculty Papers

Conclusions:

Reports to NTPR to date continue to reveal an increased incidence of birth defects in transplant recipients maintained on MPA products during gestation compared to those not maintained on these agents.

Structural birth defects consisting of microtia (ear deformity) and facial defects suggest a pattern of malformations.

Evaluation of the higher incidence of non-viable outcomes requires further study in this cohort.

Centers are encouraged to report all pregnancy exposures in transplant recipients to the NTPR.


Loss Of Stromal Caveolin-1 Independently Predicts Poor Disease-Free Survival And Time To Recurrence In Patients With Prostate Cancer, M. Wagner, A. Dasgupta, F. Sotgia, R. B. West, M. P. Lisanti, A. K. Witkiewicz 2010 Thomas Jefferson University

Loss Of Stromal Caveolin-1 Independently Predicts Poor Disease-Free Survival And Time To Recurrence In Patients With Prostate Cancer, M. Wagner, A. Dasgupta, F. Sotgia, R. B. West, M. P. Lisanti, A. K. Witkiewicz

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Results:

Of the 167 patients originally included in the study, 43 were either lost to follow up or had insufficient clinical data for comparison. Of the remaining 124 cases, 32 showed loss of stromal Cav-1. Statistical analysis revealed no significant association between stromal Cav-1 loss and the usual markers of disease severity including Gleason grade, stage and presence of metastases. Kaplan-Meier curves showed a significant association between stromal Cav-1 loss and poor disease-free survival and time to recurrence (p<0.05), but no significant association with cancer-specific survival.


Psychology Of Sport Injury : A Holistic Approach To Rehabilitating The Injured Athlete, Jennifer Jordan Utley 2010 University of St. Augustine for Health Sciences

Psychology Of Sport Injury : A Holistic Approach To Rehabilitating The Injured Athlete, Jennifer Jordan Utley

Athletic Training Collection

Sports medicine practitioners must consider both physical and mental aspects of injury to fully rehabilitate the injured athlete. The psychological distress that follows injury has been well documented and calls for a change in the rehabilitation of injured athletes.1-3 With the recent emergence of sport psychology and the emphasis on competitive sport in the United States and beyond, psychological skills are no longer solely utilized by the elite athlete; college and high school athletes are gaining instruction in the use of psychological skills from sport psychologists, coaches, and fellow teammates. Psychological skills have been shown to be effective in ...


Piloting Standardized Immediate Student Evaluation Of Lectures In Pre-Clinical Years, Meghan E. Shea, Lorrie Gehlbach, Mary L. Zanetti, Melissa A. Fischer 2010 University of Massachusetts Medical School

Piloting Standardized Immediate Student Evaluation Of Lectures In Pre-Clinical Years, Meghan E. Shea, Lorrie Gehlbach, Mary L. Zanetti, Melissa A. Fischer

Senior Scholars Program

Background: In the first and second years at the University of Massachusetts Medical school, students assess a faculty member’s lecture weeks to months after it was given. Students may not recall details of the lecture due to the delay. The timing of this feedback may impact the faculty member’s ability to institute change for their current students, as well as for the subsequent year’s students.

Objective: The purpose of the pilot was to assess the feasibility and perceived usefulness of a specific method for obtaining immediate student feedback after every lecture, and providing this feedback to faculty ...


Reduction Of Vertical Transmission Of Hiv In The Dominican Republic: Benefits Of Early Presentation For Prenatal Care, Ingrid Liff, Mario Alejandro Chevalier, Arachu Castro, Raul E. Davaro 2010 University of Massachusetts Medical School

Reduction Of Vertical Transmission Of Hiv In The Dominican Republic: Benefits Of Early Presentation For Prenatal Care, Ingrid Liff, Mario Alejandro Chevalier, Arachu Castro, Raul E. Davaro

Senior Scholars Program

Background:The impact of HIV infection on maternal and infant mortality in the Dominican Republic is unknown. The prevalence of HIV infection among pregnant women in the Dominican Republic is 1-2%, and over two-thirds of women receive prenatal care. (2,3) It is estimated that 15% of all deliveries in the Dominican Republic occur at the Hospital Maternidad Nuestra Señora de la Altagracia in Santo Domingo, making this the highest-volume maternity hospital in the country.(4)

Objectives:We conducted a study to compare the impact of HIV infection on pregnant women receiving prenatal care including highly active antiretroviral therapy (HAART ...


Attitudes Of Parents At Risk Of Inheriting Li-Fraumeni Syndrome Towards Predictive Genetic Testing In Their Minor-Aged Children., Leslie A. Newman 2010 University of Texas Graduate School of Biomedical Sciences at Houston

Attitudes Of Parents At Risk Of Inheriting Li-Fraumeni Syndrome Towards Predictive Genetic Testing In Their Minor-Aged Children., Leslie A. Newman

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Li-Fraumeni Syndrome (LFS) is a hereditary cancer syndrome which predisposes individuals to cancer beginning in childhood. These risks are spread across a lifetime, from early childhood to adulthood. Mutations in the p53 tumor suppressor gene are known to cause the majority of cases of LFS. The risk for early onset cancer in individuals with Li-Fraumeni Syndrome is high. Studies have shown that individuals with LFS have a 90% lifetime cancer risk. Children under 18 have up to a 15% chance of cancer development. Effectiveness of cancer screening and management in individuals with Li-Fraumeni Syndrome is unclear. Screening for LFS-associated cancers ...


Tamoxifen: Mechanisms Of Resistance, Cyrus McCoy Adams 2010 University of Tennessee Health Science Center

Tamoxifen: Mechanisms Of Resistance, Cyrus Mccoy Adams

Theses and Dissertations (ETD)

The role of estrogen in breast cancer has been recognized for decades. The selective estrogen receptor modulator tamoxifen was the first targeted therapy for the treatment of breast cancer. It was also the first drug approved by the FDA for the reduction of breast cancer risk. While tamoxifen has extended the lives of countless patients with breast cancer, resistance to tamoxifen remains a significant clinical problem. Work over the last two decades has greatly enhanced our understanding of the molecular mechanisms by which breast cancer cells may become resistant to tamoxifen treatment. Here I review our current understanding of the ...


Systems Biology Approach To Identifying Host Interactive Pathways Modulating The Severity Of Streptococcal Sepsis, Nourtan Fatthy Abdeltawab 2010 University of Tennessee Health Science Center

Systems Biology Approach To Identifying Host Interactive Pathways Modulating The Severity Of Streptococcal Sepsis, Nourtan Fatthy Abdeltawab

Theses and Dissertations (ETD)

Clinical outcomes of infectious diseases are controlled by complex interactions between the host and the pathogen. Epidemiological, genetic and molecular studies in my mentor’s laboratory provided evidence that in invasive Group A streptococcal (GAS) infections, genetic variations in both bacteria and patients influenced the severity of GAS sepsis. Allelic variations in class II human leukocyte antigens (HLA) contributed significantly to differences in the severity of group A streptococcal sepsis caused by the same virulent strain of the bacteria. HLA class II molecules present streptococcal superantigens (SAgs) to T cells, and variations in HLA class II molecules can strongly influence ...


Synthesis Of Novel Cannabinoid Ligands And Their Use As Anti-Glioma And Anti-Inflammatory Agents, Steven Neal Gurley 2010 University of Tennessee Health Science Center

Synthesis Of Novel Cannabinoid Ligands And Their Use As Anti-Glioma And Anti-Inflammatory Agents, Steven Neal Gurley

Theses and Dissertations (ETD)

Following the discovery of the cannabinoid receptors, research in the field of cannabinoids has grown exponentially over the last two decades. Cannabinoids have been shown to have tremendous therapeutic potential in the treatment of several pathological conditions ranging from inflammation to asthma, multiple sclerosis, Parkinson’s disease, epilepsy, glaucoma, septic shock, hemorrhagic shock, and cancer. Our research has focused on two major conditions for which cannabinoids hold great promise for drug development, namely, cancer and inflammation.

Our focus in the field of cancer has been on the devastatingly lethal brain tumor glioblastoma multiforme. Due to the high expression of the ...


T-Cell Receptor Cdr3 Sequence But Not Recognition Characteristics Distinguish Autoreactive Effector And Foxp3+ Regulatory T-Cells, Xin Liu 2010 University of Tennessee Health Science Center

T-Cell Receptor Cdr3 Sequence But Not Recognition Characteristics Distinguish Autoreactive Effector And Foxp3+ Regulatory T-Cells, Xin Liu

Theses and Dissertations (ETD)

Regulatory T-cells (Treg) play an important role in maintaining immune tolerance to self-antigens and in suppressing excessive immune responses in the host. The source, specificity, and plasticity of the forkhead box transcription factor 3 (Foxp3+) Treg and conventional T (Tconv) cell populations active at sites of autoimmune pathology are not well characterized. To evaluate this, we combined global repertoire analyses and functional assessments of isolated T-cell receptors (TCR) from TCRa retrogenic mice with autoimmune encephalomyelitis (EAE). Treg and Tconv cell TCR repertoires were distinct, and autoantigen-specific Treg and Tconv cells were enriched in diseased tissue. Autoantigen sensitivity and fine specificity ...


The Use Of Preclinical Models To Improve The Treatment Of Retinoblastoma, Katie Marie Nemeth 2010 University of Tennessee Health Science Center

The Use Of Preclinical Models To Improve The Treatment Of Retinoblastoma, Katie Marie Nemeth

Theses and Dissertations (ETD)

Rodent models play an essential role in the development of new chemotherapeutics and dosing regimes. It is often difficult to carryout a clinical study for pediatric cancers due to the small patient population. Retinoblastoma, a pediatric cancer of the eye, is one example of a pediatric cancer that can benefit from preclinical studies. Over the years various retinoblastoma rodent models have been developed used to test various combination of broad-spectrum systemic chemotherapy. It was found form these studies that the combination of topotecan and carboplatin was effective. However both drugs cause myelosuppression and therefore administrating both of these drugs systemically ...


Pain Management In Nursing Home Residents With Cancer And Dementia With And Without Hospice Services, Todd Bryant Monroe 2010 University of Tennessee Health Science Center

Pain Management In Nursing Home Residents With Cancer And Dementia With And Without Hospice Services, Todd Bryant Monroe

Theses and Dissertations (ETD)

Aims: We sought to identify differences in pain management between two groups; nursing home residents with malignant cancer and dementia with and without hospice services.

Methods: Decedent records from 2003-2009 were assessed for diagnosis of dementia and cause of death as cancer. Ten malignant cancer diagnoses were determined a priori from the CDC 2004 data on the top 10 malignant cancers for all races and genders. Fifty-five decedents from 10 nursing homes were included in the final sample. Four instruments were used: Minimum Data Set (MDS) a standardized assessment tool required of most U.S. nursing homes. A large comprehensive ...


The Effect Of L-Proline On Two Recombinant Ampa Glutamate Receptors, Adetutu Abiose Oyelami 2010 University of Tennessee Health Science Center

The Effect Of L-Proline On Two Recombinant Ampa Glutamate Receptors, Adetutu Abiose Oyelami

Theses and Dissertations (ETD)

L-proline is a non-essential amino acid and one of the major amino acid constituents of extracellular fluid. Specific mutations in genes that control proline metabolism lead to hyperprolinemia which is characterized by an increase in the level of blood and cerebrospinal fluid concentration of l-proline. In fact, deletion or mutation of the PRODH gene which codes for proline oxidase (POX) / proline dehydrogenase which is critical for proline metabolism leads to Type I hyperprolinemia and is strongly associated with schizophrenia, autism and mental retardation. Proline has previously been shown to be a low affinity agonist at glutamate and glycine receptors. Because ...


Development And Application Of Computational Tools For The Study And Optimization Of Variable Resolution X-Ray (Vrx) Computed Tomography Scanners, David Alejandro Rendon 2010 University of Tennessee Health Science Center

Development And Application Of Computational Tools For The Study And Optimization Of Variable Resolution X-Ray (Vrx) Computed Tomography Scanners, David Alejandro Rendon

Theses and Dissertations (ETD)

The overall goal of this project was to develop and apply important computerized aids for the design and implementation of Variable Resolution X-ray (VRX) CT scanners developed at the University of Tennessee, Memphis. VRX scanners take advantage of the “projective compression” principle that allows the same device to image objects of very different sizes with the same level of detail by adjusting the field of view and the reconstruction resolution.

The first part of this project aimed to develop a set of computational tools specifically tailored for the design, implementation and study of VRX scanners. This included creating a reconstruction ...


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