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Designing treatment individualization in photodynamic therapy to compensate for pharmacokinetic variability.
Photochemotherapy. Photosensitizing compounds -- Therapeutic use. Pharmacokinetics. Drugs -- Physiological effect.
The main theme of this thesis is to investigate the origins of photosensitizer pharmacokinetic variability, how this pharmacokinetic variation affects photodynamic therapy (PDT), and to search for innovative strategies to reduce the...
Dartmouth Dissertations

Combined MRI and near-infrared spectroscopy for increased specificity of breast cancer imaging / by Michael A. Mastanduno.
A yearly breast contrast-MR scan is recommended to high-risk women because of MR's high sensitivity to breast tumors. However, breast contrast-MR yields a high number of false positives that lead to expensive and sometimes unnecessary biopsy...
Dartmouth Dissertations

Functional analysis of the Runx1 C-terminal sequences.
Transcription factors. ; Hematopoiesis -- Regulation. ; Genetic transcription -- Regulation. ; DNA-binding proteins.
RUNX1 is a transcription factor regulating hematopoietic development. Study of the RUNX1 structure revealed two functional domains. The runt domain binds DNA and mediates interaction with CBFß. Sequences C terminal to the runt domain form the...
Dartmouth Dissertations

5-AMINOLEVULINIC-INDUCED PROTOPORPHYRIN.
Brain tumors account for ~2% of all cancers, with gliomas accounting for ~70% of all brain tumors. Evidence suggests that extent of resection provides both a quality of life and survival benefit to patients. Recent work has shown the utility of...
Dartmouth Dissertations

Regulation of peripheral tolerance by mast cells.
Mast cells -- Immunology. Mast cells -- Physiology. Dendritic cells. Immunological tolerance -- Molecular aspects. Medical Term Cell Degranulation.
Mast cells (MC) have until recently been regarded as pro-inflammatory, however this view changed with the observation that the absence of MC impairs the development of transplant tolerance to allografts. However, little is known about whether MC...
Dartmouth Dissertations

Integrative multi-tissue genomic analyses identify mechanisms of pathogenesis in systemic sclerosis / by Jaclyn N. Taroni
Systemic sclerosis (SSc) is a rare and often-fatal systemic autoimmune disease characterized by vasculature dysfunction, immune activation, and extracellular matrix deposition in skin and internal organs. The etiology of SSc is unknown, but it is...
Dartmouth Dissertations

FGF signaling and collagenase-1 expression in invasive melanoma cells.
Melanoma -- Genetic aspects. Fibroblast growth factors. Metalloproteinases -- Genetic aspects. Metalloproteinases -- Pathophysiology. Collagenases -- Genetic aspects. Collagenases -- Pathophysiology.
Melanoma progresses as a multi-step process, where the thickness of the lesion and depth of tumor invasion are the best prognostic indicators of clinical outcome. Degradation of the interstitial collagens in the extracellular matrix is an integral...
Dartmouth Dissertations

Investigation of trans-acting factors in AURE-mediated mRNA turnover.
Messenger RNA -- Metabolism. ; Trans-Activation (Genetics). ; RNA-protein interactions. ; Adenosine. ; Uridine. ; Lactate dehydrogenase. ; Genetic regulation. ; RNA-Binding Proteins. ; Protein processings Post-transcriptional. ; Hippel-Lindau...
Post-transcriptional pathways provide a major means of regulating eukaryotic gene expression. Reiterations of the AU-rich element (AURE) located within the 3' UTR of many labile cytokine and proto-oncogene mRNA serve as signals for rapid...
Dartmouth Dissertations

Von Hippel Lindau (VHL) tumor suppressor regulation of MT1-MMP in renal cell carcinoma.
Antioncogenes. Metalloproteinases. Genetic regulation. Kidneys -- Cancer.
Dartmouth Dissertations

The pathophysiology of transforming growth factor-beta in breast cancer.
Transforming growth factors-beta -- Pathophysiology. ; Breast -- Cancer -- Pathophysiology.
Dartmouth Dissertations

The role of p53 in retinoic acid-induced differentiation of human germ cell tumors.
p53 antioncogene -- Regulation. ; Retinoids -- Physiological effect. ; Retinoids -- Receptors. ; Cell differentiation -- Molecular aspects. ; Genetic transcription -- Regulation. ; Germ cells -- Tumors. ; Receptors.
The retinoids exert potent growth and differentiation effects on normal, embryonic and neoplastic cells. Although retinoids are known to regulate gene transcription through activation of retinoid receptors, the direct target genes of retinoid...
Dartmouth Dissertations

Insights into the assembly and organization of higher-order septin structures.
Septins. ; Proteins -- Structure. ; Fluorescence spectroscopy. ; Molecular biology -- Instruments. ; GTP-Binding Proteins.
Dartmouth Dissertations

FGF2 in endothelial cell migration, intracellular signalling and receptor endocytosis.
Fibroblast growth factors. Rho GTPases. Cell receptors. Integrins -- Physiological effect. Endocytosis. Vascular endothelium. Cellular signal transduction.
Endothelial cell migration is an important element of a number of biological processes, including angiogenesis. The fibroblast growth factors (FGFs) are a family of angiogenic heparan-binding proteins that potently induce endothelial migration....
Dartmouth Dissertations

Re-programming tumor-infiltrating dendritic cells in situ via RNAi elicits therapeutic immunity against ovarian cancer.
Ovaries -- Cancer -- Immunotherapy. Dendritic cells. Small interfering RNA. Nanoparticles -- Therapeutic use. Medical Term Ovarian Neoplasms -- therapy. RNA Interference.
Current therapies for ovarian carcinoma are based on surgical debulking followed by chemotherapy. After more than three decades implementing treatments that selectively target the tumor cell, the 5-year survival rate for metastatic ovarian cancer...
Dartmouth Dissertations

Unraveling mechanisms underlying myeloid-derived suppressor cell orchestration of ovarian cancer progression
Suppressor cells -- Cellular immunity. -- Interleukin-10 -- Pathophysiology -- Ovaries -- Cancer -- Immunological aspects. -- Myeloid cells -- immunology -- Ovarian Neoplasms -- immunology.
Dartmouth Dissertations

Splice variation-specific cellular and biochemical function of the formin INF2
Formins are actin nucleators that modulate the nucleation and elongation of actin filaments. Formin homology 1 (FH1) and formin homology 2 (FH2) domains play a key role in formin-mediated actin dynamics. INF2 is a unique formin which can both...
Dartmouth Dissertations

Acquisition and registration of 3D optical surface scanning, MRI, and microwave tomographic imaging for improved clinical breast imaging and surgical planning / by Matthew John Pallone.
Continual improvements to clinical breast imaging technologies have led to ever earlier detections and increasingly accurate localizations of female breast cancers. While these advancements have certainly improved the prognoses of many patients,...
Dartmouth Dissertations

MicroRNA-10b promotes pancreatic cancer cell invasion by suppressing TIP30 and enhancing EGF and TGF-[beta] actions / by Haoxu Ouyang
MicroRNA-10b (miR-10b) is considered a marker of disease aggressiveness in pancreatic ductal adenocarcinoma (PDAC), in view of the fact that lower levels of miR-10b are associated with better response to neoadjuvant therapy, likelihood of surgical...
Dartmouth Dissertations

Phosphoproteomic strategies to identify aberrant kinase signaling in lung cancer / by Devin Karl Schweppe
Lung cancer is the leading cause of cancer-related death in the USA and worldwide causing 160,000 and 1.5 million deaths per year, respectively. Due to the late stage of diagnosis, poor efficacy of chemotherapies (targeted and pleiotropic), and...
Dartmouth Dissertations

Endogenous leukocyte activation by chimeric antigen receptor T cell immunotherapy / by Paul Spear.
Many protocols for adoptive T cell therapy (ACT) include preparative conditioning strategies to deplete host lymphocytes prior to T cell infusion. Total body irradiation and high-dose chemotherapy regimens not only relieve immunosuppression, but...
Dartmouth Dissertations

Brain repair after trauma : birth and migration of immature neurons after focal traumatic brain injury in piglets and human children / by Sabrina Rose Taylor.
Traumatic brain injury (TBI) is the leading cause of acquired disability in children, yet innate repair mechanisms are incompletely understood. A possible innate mechanism to repair injury after insult is neurogenesis - the birth, migration,...
Dartmouth Dissertations

Chemico-physical and pharmacologic factors that influence delivery of IONPs to tumors in rodent breast cancer models / by Jennifer Tate.
Nanoparticles have made significant advances in recent years in the realm of cancer therapy. These nanoparticles typically range in size from 10-250nm in diameter, allowing for differential systemic-based biodistribution. The enhanced permeability...
Dartmouth Dissertations

Noninvasive fluorescence monitoring for functional assessment of murine glioma treatment.
Gliomas -- Immunotherapy -- Evaluation. Fluorescence spectroscopy. Diagnosis.
Molecular optical imaging in vivo has potential for functional assessment of tumor tissue at the cellular and subcellular level. Advances in biological understanding of genomics and proteomics have increased the knowledge of possible cellular...
Dartmouth Dissertations

Examining functional variation in oncogene biology : the role of somatic mutations and germline variation on c-Myc and c-Myb / by Scott Andrew Turner.
The identification and characterization of functional genetic variation is essential for future advances in molecular diagnostics, pharmacogenomics, and personalized medicine. Recent attempts at identifying nucleotide level variation (somatic...
Dartmouth Dissertations

Dissecting the heterogeneity of breast tumor subtypes / by Nima Pouladi.
Breast cancer is the most common cancer in women. The discovery of breast tumor subtypes and the subsequent development of treatments aimed at them has allowed a reduction in the mortality of breast cancer. However, tumors with similar...
Dartmouth Dissertations

The SERM, Arzoxifene, and the rexinoid, LG100268, cooperate to prevent estrogen receptor-positive and -negative breast cancer as well as colon cancer.
Estrogen -- Receptors -- Regulation. Selective estrogen receptor modulators. Receptor-ligand complexes. Breast -- Cancer -- Chemoprevention. Colon (Anatomy) -- Cancer -- Chemoprevention.
We have previously shown that the selective estrogen receptor modulator, Arzoxifene (Arz), and the rexinoid, LG100268 (268) synergistically prevent breast cancer in an ER+ breast cancer model. This study was designed to determine the mechanism of...
Dartmouth Dissertations

Combined digital breast tomosynthesis and near-infrared spectral tomography for breast lesion characterization / by Kelly E. Michaelsen.
Annual screening mammograms are recommended for all women above 40 years of age for early detection of breast cancer, and are known to improve cancer mortality rates. However, mammography is hampered by low sensitivity and a high rate of false...
Dartmouth Dissertations

Identification and characterization of signaling pathways underlying the tumorigenic activity of [Delta]Np63[alpha] in breast cancer stem cells / by Amanda Lynn Balboni.
Studies presented in this dissertation focus on the transcriptional targets and cellular functions of [Delta]Np63[alpha], the predominant TP63 isoform expressed in epithelial stem cell compartments. TP63, a member of the p53 family of...
Dartmouth Dissertations

The causes and consequences of regulation of [Delta]NP63[alpha] in mammary and breast cancer stem cells / by Andrew Joseph DeCastro.
Despite the array of targeted therapeutics that currently exist to combat breast cancer, disease progression leading to metastasis, and tumor recurrence still remains a significant clinical challenge. Efforts to identify novel pathways and...
Dartmouth Dissertations

Constitutively activated PI3K signaling accelerates tumor initiation and progression in breast and lung cancers / by Mee Rie Sheen.
Phosphatidylinositol 3-kinase (PI3K) is a major positive regulator of the PI3K signaling pathway that regulates many important cellular functions including growth, proliferation, survival, metabolism, and angiogenesis. The PIK3CA gene, encoding the...
Dartmouth Dissertations

Quantifying optical tomography methods for biomolecular sensing / by Jennifer-Lynn H. Demers.
Diffuse optical imaging techniques can be combined with standard imaging technologies such as computed tomography (CT) and magnetic resonance (MR) imaging to allow measurement of spectroscopic signals pertaining to the molecular components of...
Dartmouth Dissertations

The role of gut commensals in regulating susceptibility to acute liver damage / by Stela Celaj.
Liver disease of different etiologies confers significant morbidity and mortality and hence it constitutes a major health concern worldwide. Stemming from a range of causes, such as viral, drug-induced, alcoholic, or autoimmune, the rate of...
Dartmouth Dissertations

Links and regulatory loops between phospholipase C activity and colonization by the O2-responsive regulator Anr in Pseudomonas aeruginosa / by Angelyca A. Jackson.
Pseudomonas aeruginosa is a virulent opportunistic pathogen that is frequently cultured from infectious sites, and is estimated to cause ~12% of nosocomial infections worldwide [1]. P. aeruginosa infections occur in a majority of adults with the...
Dartmouth Dissertations

Exercise and the brain : impacts on cognition neural function and mental health / by Andrea M. Robinson.
It has been well established that physical exercise has broad impacts across the lifespan, including improved cognition, brain function, and mental health. Studies investigating the mechanism underlying the cognitive enhancing effect of exercise...
Dartmouth Dissertations

Novel dimensions in a fluid genome : an integrative risk analysis for cancers of the bladder and breast / by Asaf Wyszynski.
The present thesis is focused on developing a better understanding of factors driving disease biology and overall risk using cancers of the bladder and breast as model systems. As no single approach was likely to unravel the complexities of these...
Dartmouth Dissertations

Runx1 is required in vascular endothelial cadherin expressing cells for hematopoietic stem cell emergence.
Transcription factors. Hematopoietic stem cells -- Genetic aspects. Hematopoiesis -- Regulation. DNA-binding proteins. Vascular endothelium.
Hematopoietic stem cells (HSCs) are the cells that can give rise to all different lineages of differentiated/mature blood cells. HSCs are capable of self-renewal and maintaining the homeostasis of differentiated cells for specific functions. The...
Dartmouth Dissertations

ID4 promotes the growth of glioblastoma multiforme by mediating MGP-enhanced angiogenesis.
Glioblastoma multiforme. DNA-binding proteins. Transcription factors. Extracellular matrix proteins. Neovascularization.
ID proteins are naturally occurring dominant negative HLH-transcription factors that are highly expressed during development but generally not expressed in adult tissue except for selected cell types and some stem cells. Also, aberrant expression...
Dartmouth Dissertations

Cif, a novel Pseudomonas aeruginosa toxin.
Pseudomonas aeruginosa infections -- Pathogenesis. Hydrolases. Membrane proteins -- Physiological transport. Genetic regulation. Epoxide Hydrolases -- genetics.
Pseudomonas aeruginosa is the leading cause of morbidity and mortality amongst cystic fibrosis (CF) patients. Following initial colonization of the CF lung by P. aeruginosa , the bacterium establishes chronic, long-term infections. Chronic P....
Dartmouth Dissertations

Treatment planning software for the Dartmouth IMAAH system
Cancer -- Radiotherapy -- Computer programs; Microwave antennas -- Physiological effect -- Computer programs
Dartmouth Dissertations

Activation of vascular endothelial cells in response to mineral fibers.
Asbestosis -- Pathophysiology. Asbestosis -- Molecular aspects. Pulmonary endothelium -- Genetic aspects. Endothelium -- Effect of asbestos on. Fibers -- Toxicology.
Dartmouth Dissertations

Hematopoiesis in the allantois and chorion.
Hematopoietic stem cells. ; Transcription factors. Placenta -- Cytology. Chorion -- Cytology. ; Cellular signal transduction.
The placenta is the extra-embryonic tissue that mediates the exchange of oxygen and nutrients between the fetus and mother. It was shown that the placenta is a source of hematopoietic stem cells (HSCs). However, it is not known whether the placenta...
Dartmouth Dissertations

A generalized least-squares minimization method for near infrared diffuse optical tomography.
Optical tomography. ; Near infrared spectroscopy. ; Image analysis -- Mathematical models. ; Imaging systems -- Image quality -- Mathematical models. ; Image reconstruction -- Mathematical models. ; Least squares. Breast -- Tomography.
Diffuse optical tomography (DOT) has the potential to become a non-invasive and non-ionizing diagnostic imaging technique for breast cancer imaging. DOT uses near-infrared (NIR) light to illuminate the breast, generally through the use of fiber...
Dartmouth Dissertations

Steady state NMR imaging of cerebral blood volume as an index of chronic hypoxia induced angiogenesis.
Neovascularization. Brain -- Blood-vessels -- Magnetic resonance imaging. Blood volume -- Measurement. Cerebral circulation -- Measurement. Anoxemia. Blood Volume Determination -- methods.
Angiogenesis is part of the natural defense mechanism in brain against hypoxia and ischemia. Animal models and methods for the non-invasive investigation of cerebral angiogenesis are needed. This thesis addresses the hypothesis that steady state,...
Dartmouth Dissertations

Single nucleotide polymorphisms in the human prostacyclin gene: implications for cardiovascular disease and genetic mutagenesis.
Prostacyclin -- Receptors. Chromosome polymorphism. Cardiovascular system -- Diseases -- Genetic aspects. Polymorphism.
Prostacyclin (PGI 2 ) is a major product of COX-2 catalyzed metabolism of arachidonic acid in the endothelium and has been shown to be atheroprotective. PGI 2 signals though its G-coupled protein receptor (GPCR) the human Prostacyclin receptor...
Dartmouth Dissertations

Harnassing natural killer cell receptors for tumor immunotherapy / by Ming-Ru Wu
Despite all the efforts and progress in cancer research, cancer remains a devastating disease. After more than 120 years of research, immunotherapy provides a realistic hope to cure cancer. Several formats of immunotherapy, such as...
Dartmouth Dissertations

The novel p53 target gene STK17A : implications for cancer therapy / by Pingping Mao
Testicular germ cell tumors (TGCTs) are highly curable with cisplatin-based therapy. The p53 tumor suppressor is induced in response to a variety of cellular stresses. Our previous work has implicated an important role for p53 in TGCT...
Dartmouth Dissertations

Design of a magnetic field compatible, high-performance optical breast imaging system for MRI-guided optical spectroscopy / by Fadi El-Ghussein
Multimodality imaging is becoming the standard of care for research and clinical studies. Such an approach is able to provide complementary information which can detect and characterize tumors. Advancing instrumentation for diffuse near-infrared...
Dartmouth Dissertations

Novel approaches to targeting innate immunity for cancer immunotherapy / by Patrick H. Lizotte
Many kinds of cancer, and almost universally metastatic cancer, are refractory to treatment by conventional methods: surgery, radiation, and non-specific cytotoxic chemotherapy. The dawn of the age of personalized medicine presaged 15 years ago...
Dartmouth Dissertations

Microwave imaging spectroscopy for breast cancer diagnosis.
Microwave spectroscopy. Imaging systems -- Design and construction. Diagnostic imaging -- Digital techniques. Breast -- Cancer -- Diagnosis. Microwave imaging in medicine.
Microwave spectroscopy has been investigated as a possible modality for breast imaging because of the significant contrast in electrical properties between normal and malignant tissue over the microwave spectrum. A liquid-coupled, non-contacting...
Dartmouth Dissertations

CXCR3 and its cognate-chemokine expression : implications for cancer immunotherapy / by Eleanor Clancy-Thompson
Despite immunogenicity, melanoma-specific vaccines have demonstrated minimal clinical efficacy in patients with established disease, but enhance survival when administered in the adjuvant setting. It has been shown that T cell infiltration of...
Dartmouth Dissertations

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