Therapeutics Commons^™

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

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 …

Optimization Algorithms For Functional Deimmunization Of Therapeutic Proteins, Andrew S. Parker, Wei Zheng, Karl E. Griswold, Chris Bailey-Kellogg

Dartmouth Scholarship

To develop protein therapeutics from exogenous sources, it is necessary to mitigate the risks of eliciting an anti-biotherapeutic immune response. A key aspect of the response is the recognition and surface display by antigen-presenting cells of epitopes, short peptide fragments derived from the foreign protein. Thus, developing minimal-epitope variants represents a powerful approach to deimmunizing protein therapeutics. Critically, mutations selected to reduce immunogenicity must not interfere with the protein's therapeutic activity.

The Power Of Empowerment: An Icf-Based Model To Improve Self-Efficacy And Upper Extremity Function Of Survivors Of Breast Cancer, Mary Insana Fisher, Dana Howell

Physical Therapy Faculty Publications

Breast cancer is one of the most frequently diagnosed cancers among women. Breast cancer treatments often negatively impact the function of the arm, and quality of life and upper extremity function does not always return to a prediagnosis level. Survivors of breast cancer may also experience feelings of diminished self-efficacy related to functional deficits resulting from their physical limitations. The International Classification of Functioning (ICF) provides a framework for rehabilitation practitioners to address physical and psychological impairments, activity limitations, and participation restrictions. Patient outcomes may be improved by fostering self-efficacy through empowerment. This paper explores how the ICF model and …

Wnt Pathway Reprogramming During Human Embryonal Carcinoma Differentiation And Potential For Therapeutic Targeting, Grace E. Snow, Allison C. Kasper, Alexander M. Busch, Elisabeth Schwarz, Katherine E. Ewings, Thomas Bee, Michael J. Spinella, Ethan Dmitrovsky, Sarah J. Freemantle

Dartmouth Scholarship

Testicular germ cell tumors (TGCTs) are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC) that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES) cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency.

Peer-Led Team Learning: A Prospective Method For Increasing Critical Thinking In Undergraduate Science Courses, Ian J. Quitadamo, C. Jayne Brahler, Gregory J. Crouch

Physical Therapy Faculty Publications

This study examined the impact of peer-led team learning (PLTL) on critical thinking gains in science and math courses at a research university in the Pacific Northwest.

Chronic Elbow Dislocation Treated With Open Reduction And Lateral Ulnar Collateral Ligament Reconstruction, Louis Joseph Rubino, Michael A. Herbenick, Ryan P. Finnan, Philip A. Anloague

Physical Therapy Faculty Publications

In the United States, chronic unreduced elbow dislocations are rare injuries. We report the successful short-term outcome of a chronic elbow dislocation treated with open reduction and lateral ulnar collateral ligament reconstruction using a split semitendinosus allograft in a figure-of-8 technique without use of hinged external fixation. The authors have obtained the patient’s written informed consent for print and electronic publication of the case report.

Hmgb1 Mediates Endogenous Tlr2 Activation And Brain Tumor Regression, James Curtin, Naiyou Liu, Marianela Candolfi, Weidong Xiong, Hikmat Assi, Kader Yagiz, Matthew Edwards, Kathrin Michelsen, Kurt Kroeger, Chunyan Liu, Akm Ghulam Muhammad, Mary Clark, Moshe Arditi, Begonya Comin-Anduix, Antoni Ribas, Pedro Lowenstein, Maria Castro

Articles

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor that carries a 5-y survival rate of 5%. Attempts at eliciting a clinically relevant anti-GBM immune response in brain tumor patients have met with limited success, which is due to brain immune privilege, tumor immune evasion, and a paucity of dendritic cells (DCs) within the central nervous system. Herein we uncovered a novel pathway for the activation of an effective anti-GBM immune response mediated by high-mobility-group box 1 (HMGB1), an alarmin protein released from dying tumor cells, which acts as an endogenous ligand for Toll-like receptor 2 (TLR2) signaling …

Treg Depletion Inhibits Efficacy Of Cancer Immunotherapy: Implications For Clinical Trials., James Curtin, Marianela Candolfi, Tamer Fakhouri, Chunyan Liu, Anderson Alden, Matthew Edwards, Pedro Lowenstein, Maria Castro

Articles

BACKGROUND: Regulatory T lymphocytes (Treg) infiltrate human glioblastoma (GBM); are involved in tumor progression and correlate with tumor grade. Transient elimination of Tregs using CD25 depleting antibodies (PC61) has been found to mediate GBM regression in preclinical models of brain tumors. Clinical trials that combine Treg depletion with tumor vaccination are underway to determine whether transient Treg depletion can enhance anti-tumor immune responses and improve long term survival in cancer patients. FINDINGS: Using a syngeneic intracrabial glioblastoma (GBM) mouse model we show that systemic depletion of Tregs 15 days after tumor implantation using PC61 resulted in a decrease in Tregs …

High Dietary Fat Intake Is Not Associated With High Levels Of Circulating Lipoproteins Or Total Cholesterol, C. Jayne Brahler, C. Wilson, Janine Baer

Physical Therapy Faculty Publications

The objective of this study was to determine the association between dietary intake of fats, waist to hip ratio (WHR), body mass index (BMI), and blood lipoproteins and total cholesterol (TC) using food frequency data in one group of apparently healthy, urban African American women and their daughters (n = 110). Subjects were fasted when blood was drawn, waist and hip circumferences and body weight and height were measured, and WHR and BMI were calculated.

Average daily total fat intakes were 91.46 g and 77.83 g for mothers and daughters, respectively, but average LDL levels of 104.4 g/L and 103.1 …

Factors That Influence The Blood Flow Response Of Skin To Electrical Stimulation, Abdul-Majeed Raja Al-Malty

Loma Linda University Electronic Theses, Dissertations & Projects

Female reproductive hormones, aging, global heating and local heating are factors affecting skin blood flow (SBF), but their effect on electrical stimulation (ES) has never been examined until the present investigation. To investigate female reproductive hormones, nine women (age= 25.6±3.5 years) with a normal menstrual cycle (MC) underwent ES in thermoneutral (25°±0.5°C) and warm environments (35°±0.5°C). To investigate aging, ES was applied on active young (n=15, age=32.1±8.3 years) and old (n=8, 64.5±6.2 years) groups in thermoneutral and warm environments. To investigate the effect of global and local heating, groups of 15 and 18 subjects (age= 18-40 years) experienced ES under …

Disaggregating The Relative Influence Of Genetic, Environmental And Individual Factors On Ldl And Hdl Cholesterols And Bmi For A Sample Of African American (Aa) Mothers And Daughters, C. Jayne Brahler, Jewel Harden, Michelle Mchone, Matthew Soules, Eric Evans, Ann Alyanak, Fred Diakpieng, Paul M. Vanderburgh

Health and Sport Science Faculty Publications

There are many reports about the associations between blood lipids, body mass index (BMI) and dietary cholesterol intakes both within the individual and between related individuals. The purpose of this descriptive research project was to investigate the relationships between LDL and HDL cholesterols, body mass index and dietary cholesterol intakes for a sample of African American (AA) mothers and their daughters and to attempt to separate the contribution of genetic versus environmental factors. Mother and daughter participants (n =42 and 66, respectively) were 12-14-hours fasted when blood samples were drawn, heights and weights measured, and 24 hour food recalls completed.

Beyond Bloodletting: Fda Gives Leeches A Medical Makeover, Carol Rados

Harold W. Manter Laboratory of Parasitology: Library Materials

In June 2004, the Food and Drug Administration cleared the first application for leeches (Hirudo medicinalis) to be used in modern medicine as medical devices. By definition, a medical device is an article intended to diagnose, cure, treat, prevent, or mitigate a disease or condition, or to affect a function or structure of the body, that does not achieve its primary effect through a chemical action and is not metabolized.

Effect Of Anti-Tgfß1 And Pycnogenol® On Scar Formation In Rats, Pilseong Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Wound healing is a complex biologic process that involves chemotaxis and division of cells, neovascularization, synthesis of extracellular matrix proteins, and remodeling of the repaired tissues. Of equal importance is the restoration of normal tissue structure and function without scar formation. The aim of this study was to find out the clinical effects of anti-TGFß1 and Pycnogenol® on scarless wound healing on rat skin.

An acute incision wound model was used with 20 healthy rats. Four incisions were made on each rat's skin and 4 different variables were applied by local infiltration. The four variables were anti-TGFß1, Pycnogenol®, PBS, and …

Qtc Is Associated With Obesity And Physical Activity Level For African American Females, C. Jayne Brahler

Health and Sport Science Faculty Publications

Long QT syndrome (LQTS) is an independent risk factor for cardiovascular or ischemic disease mortality. Obesity as a cause for acquired LQTS in otherwise healthy individuals is rapidly gaining the attention of the scientific community. African American people have a higher incidence of obesity compared to Caucasians, yet race-specific information is not available for their prevalence of LQTS. Chronic physical activity can help reduce the incidence of obesity, yet little is known about the effects of chronic physical activity on acquired LQTS. Subjects in this study were a volunteer sample of African American mothers (21-53 yr, n = 44) and …

Patterns Of Hydroxyproline Excretion In Ovariectomized And Estrogen Treated Rats, Gregg Horras

Presidential Scholars Theses (1990 – 2006)

If nuclear binding sites for estrogens exist in bone cells, then the origin of estrogen-deficiency-induced osteopenia may be at the level of bone matrix protein synthesis. Since collagen is the most abundant protein in the bone matrix, and since hydroxyproline is an imino acid nearly exclusive to collagen, a monitoring of the metabolism of hydroxyproline in ovariectomized and estrogen treated rats may provide insight into the patterns of estrogen-deficiency-induced osteopenia. The purpose of our study was to test the hypothesis that ovariectomy will increase urinary hydroxyproline excretion in the rat and that this increase will be reversed by estrogen treatment …

The Circulatory Effects Of Histamine, Fred B. Moor

Medical Arts and Sciences: A Scientific Journal of the College of Medical Evangelists

No abstract provided.