Dartmouth Digital Library Program

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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

Characterizing the impact of single nucleotide variation in breast cancer / by Kinjal Desai
Genome sequencing technology has enabled the identification of genetic variants that are linked with cancer phenotypes, whether these are somatically acquired mutations or common inherited single nucleotide polymorphisms (SNPs). Whereas coding...
Dartmouth Dissertations

Transgenic cyclin E murine models as discovery tools for lung cancer biology, therapy, and prevention.
Lungs -- Cancer -- Genetic aspects. ; Cyclins -- Pathophysiology. ; Transgenic mice. ; Pharmacogenomics. ; Cyclin E -- genetics.
Dartmouth Dissertations

Functional analysis of cell cycle genes by genome-wide expression data and meta-analysis of RNAi screens.
Cell cycle -- Regulation. ; Genetic regulation. ; Small interfering RNA. ; Spindle (Cell division). ; Epithelial cells -- Genetic aspects. ; Mammary glands -- Cytology. ; Cell lines. ; Cell Cycle -- genetics. ; Genes cdc. ; RNA Interference. ;...
Successful traversal of the cell division cycle is paramount for maintaining a cell's genomic integrity and fitness. To ensure the faithful replication and segregation of the genome, cellular components, and cytoplasm, eukaryotes have evolved a...
Dartmouth Dissertations

Genome-wide analysis of human cell cycle gene expression and its regulation by forkhead box genes.
Cell cycle -- Regulation.; Transcription factors. ; Luciferases. ; Forkhead Transcription Factors -- genetics.
Successful completion of the cell division cycle is critical for cellular duplication and survival. There are many regulators and checkpoints to ensure the proper cell cycle progression. Disruption of the machinery involved in completion, error...
Dartmouth Dissertations

A role for TP63 in breast cancer initiation.
Despite the availability of targeted therapies, breast cancer metastasis and recurrence remain clinically challenging problems. Understanding the function of stem cells in this disease may lead to identification of genetic pathways underlying...
Dartmouth Dissertations

Investigation of the ISG15 deisgylase UBP43 in carcinogenesis : tumor suppressor or oncogene? / by Fadzai Chinyengetere.
ISGylation is a type 1 interferon-regulated process that involves conjugation of ISG15, an ubiquitin-like protein, to target proteins. This posttranslational modification is reversed by a deubiquitinase known as UBP43 or USP18. UBP43 is deregulated...
Dartmouth Dissertations

Targeting kinetochore-microtubule stability affects chromosome segregation and tumor growth in mice / by Christopher D. Laucius
Chromosomal instability (CIN) is defined as a high rate of whole chromosome loss or gain and is a hallmark of many aneuploid solid tumors. CIN positively correlates with poor patient prognosis and chemotherapeutic resistance. The persistence of...
Dartmouth Dissertations

Analysis of aberrant cell cycle regulation in pancreatic ductal adenocarcinoma uncovers novel thereapeutic approaches
Aberrant activation of cyclin D-Cdk4/6 is commonly found in pancreatic ductal adenocarcinoma (PDAC). Here, we show that PD-0332991, a highly specific inhibitor for Cdk4 and Cdk6, exerted growth inhibitory effects on human PDAC cell lines....
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

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

14-3-3 sigma modulates pancreatic cancer cell survival and invasiveness.
Pancreas -- Cancer -- Pathophysiology. Pancreatic duct -- Pathophysiology. Proteins -- Pathophysiology. 14-3-3 Proteins -- physiology. Pancreatic Neoplasms -- pathology.
14-3-3 is down-regulated in certain human cancers, but its expression is increased in pancreatic ductal adenocarcinoma (PDAC). The purpose of the present study was to investigate the potential role of 14-3-3σ in PDAC. The levels of 14-3-3...
Dartmouth Dissertations

Population structure, ancestry, and environmental predictors of lung and bladder cancer in New Hampshire.
Lungs -- Cancer -- New Hampshire. Bladder -- Cancer -- New Hampshire. Cancer -- Epidemiology. Cancer -- Environmental aspects -- New Hampshire. Cancer -- Genetic aspects
Complex diseases such as lung cancer are most commonly the result of environmental variables acting on an individual's genetic background. Those environmental variables may be found in the external environment, such as exposures to carcinogenic...
Dartmouth Dissertations

MLL1 plays an essential role in steady-state hematopoiesis and B Lymphopoiesis / by Tao Gan.
The Mixed Lineage Leukemia (MLL1) gene was first cloned as a hot spot of chromosomal translocations in acute leukemia. More than 70 fusion proteins of MLL1 have been described in both lymphoid and myeloid leukemia and many are highly associated...
Dartmouth Dissertations

Investigations of a novel retinoid target gene : G0S2 / by Tian Ma.
In a search for target genes for all-trans retinoic acid (RA) treatment of acute promyelocytic leukemia (APL), G0/G1 switch gene 2 (G0S2) was found to be one of the most prominently and rapidly induced species. G0S2 is a small, basic protein with...
Dartmouth Dissertations

Exploiting the proteome to improve the genome-wide genetic analysis of epistasis in common human diseases.
Epistasis (Genetics) Protein-protein interactions -- Data processing. Proteomics -- Data processing. Diseases -- Risk factors -- Statistical methods. Chromosome polymorphism. Software measurement -- Evaluation. Computational biology -- Methodology.
The completion of the Human Genome Project in 2003 and the HapMap Project in 2005 has broadened the spectrum of genetic research tools that allow researchers to conduct genome-wide association studies (GWAS) for detecting genetic variants that...
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

The importance of p53-dependent transcriptional responses in the differentiation and curability of human embryonal carcinoma.
Testis -- Cancer -- Genetic aspects. p53 antioncogene -- Regulation. Embryonal tumors -- Pathophysiology. Germ cells -- Tumors -- Pathophysiology. Cisplatin -- Mechanism of action. Tretinoin. Testicular Neoplasms -- in children. Neoplasms
Dartmouth Dissertations

On the leukemogenic mechanisms of core binding factor translocation products.
Transcription factors -- Pathophysiology. Myeloid leukemia -- Genetic aspects. Genetic transcription -- Regulation.
Core binding factor translocations and inversions are among the most frequently identified mutations in acute myeloid leukemia. We present work that characterizes the functional contributions of domains within the fusion proteins resulting from the...
Dartmouth Dissertations

Leading quality care transformation through involving everyone in improving care
Background: With the science and transparency of quality measurement unfolding, and economic forces changing, hospital leaders seek to aggressively improve their systems' care quality. Successful organizational transformations will engage everyone...
Dartmouth Dissertations

Mechanisms of a glial modulating agent, propentofylline :potential new treatment for glioblastoma multiforme
Glioblastoma multiforme is the most common and aggressive primary brain tumor with a very poor prognosis despite multi-modalities of treatment. As a result, there is a critical need to develop alternative therapies. Propentofylline (PPF) is a...
Dartmouth Dissertations

Pharmacological targeting of Wnt and Hedgehog pathways in lung cancer / by Alexander M. Busch
The Hedgehog (Hh) and Wnt pathways are key biological signaling pathways responsible for embryonic development, cellular proliferation, stem cell maintenance and self-renewal, and adult somatic tissue homeostasis. Because these pathways serve as...
Dartmouth Dissertations

Molecular mechanisms of estrogen receptor regulation and signaling in human monocytes and macrophages.
Estradiol -- Physiological effect. Estrogen -- Receptors -- Regulation. Macrophages. Monocytes. Cellular signal transduction. Tumor necrosis factor. NF-kappa B (DNA-binding protein) Endometrium -- Immunology. Endometrium -- Physiology.
Sexual dimorphism in immune responses suggests that sex steroid hormones are involved in modulating immune mechanisms in vivo . Sepsis-related mortality rates increase after menopause, implicating 17ß-estradiol (estradiol) as an important factor...
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

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

Characterization of cancer risk and response to immunotherapy through pathway-based genomic analyses / by David C. Qian
For most cancers, the genetic mechanisms that predispose normal cells to neoplastic transformation and tumor cells to therapeutic eradication are poorly understood. High throughput genotyping technologies have allowed the rapid discovery of...
Dartmouth Dissertations

The distribution and motions of galaxies in the main ridge of the Perseus-Pisces supercluster.
Galaxies -- Motion in line of sight. ; Galaxies -- Clusters. ; Superclusters.
Dartmouth Dissertations

Targeting anaphase catastrophe through CDK inhibition in lung cancer / by Shanhu Hu
Aneuploidy is frequently detected in human cancers and is implicated in carcinogenesis. Pharmacological targeting of aneuploidy is an attractive therapeutic strategy, as this would preferentially eliminate malignant over normal cells. Our prior...
Dartmouth Dissertations

Large bowel polyps: aspects of epidemiology and diagnosis.
Intestine, Large -- Cancer -- Epidemiology. ; Intestine.
Colorectal cancer is the fourth most common cancer diagnosis and the second leading cause of cancer-related death in the United States. Most colorectal cancers are believed to develop from precursor lesions known as colorectal adenomas....
Dartmouth Dissertations

Budding yeast discovery tools for neurofibromatosis type 1.
Neurofibromatosis type 1 (NF1) is a genetic disorder that predisposes affected individuals to a variety of benign and malignant nervous system tumors. NF1 is caused by a mutation in the NF1 tumor suppressor gene, which encodes neurofibromin, a...
Dartmouth Dissertations

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