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Association Of Race/Ethnicity And Population Density With Disparities In Timeliness Of Rectal Cancer Therapy, Susanna S. Hill Apr 2020

Association Of Race/Ethnicity And Population Density With Disparities In Timeliness Of Rectal Cancer Therapy, Susanna S. Hill

GSBS Dissertations and Theses

Objective:

Access to care is key to effective rectal cancer treatment. We hypothesized that ethnic/racial minorities living in high population density areas would have the greatest delays in cancer care compared to whites living in medium population density areas.

Methods:

Using 2004-2016 National Cancer DataBase data, we identified stage I-III patients with invasive rectal adenocarcinoma who underwent surgery. The data were analyzed by race/ethnicity (whites, blacks, or Hispanics) and population density (metropolitan or urban/rural). Multivariable ANCOVA was performed to evaluate the duration of time from diagnosis to surgery.

Results:

The study population consisted of 76,131 patients ...


Tumor-Stroma Interactions Differentially Alter Drug Sensitivity Based On The Origin Of Stromal Cells, Benjamin D. Landry Oct 2018

Tumor-Stroma Interactions Differentially Alter Drug Sensitivity Based On The Origin Of Stromal Cells, Benjamin D. Landry

GSBS Dissertations and Theses

Tumor heterogeneity observed between patients has made it challenging to develop universal or broadly effective cancer therapies. Therefore, an ever-growing movement within cancer research aims to tailor cancer therapies to individual patients or specific tumor subtypes. Tumor stratification is generally dictated by the genomic mutation status of the tumor cells themselves. Importantly, non-genetic influences – such as interactions between tumor cells and other components of the tumor microenvironment – have largely been ignored. Therefore, in an effort to increase treatment predictability and efficacy, we investigated how tumor-stroma interactions contribute to drug sensitivity and drug resistance.

I designed a high throughput co-culture screening ...


Targeting Drug Resistance In Chronic Myeloid Leukemia: A Dissertation, Leyuan Ma Nov 2016

Targeting Drug Resistance In Chronic Myeloid Leukemia: A Dissertation, Leyuan Ma

GSBS Dissertations and Theses

Inhibiting BCR-ABL kinase activity with tyrosine kinase inhibitors (TKIs) has been the frontline therapy for CML. Resistance to TKIs frequently occurs, but the mechanisms remain elusive.

First, to uncover survival pathways involved in TKI resistance in CML, I conducted a genome-wide RNAi screen in human CML cells to identify genes governing cellular sensitivity to the first generation TKI called IM (Gleevec). I identified genes converging on and activating the MEK/ERK pathway through transcriptional up-regulation of PRKCH. Combining IM with a MEK inhibitor synergistically kills TKI-resistant CML cells and CML stem cells.

Next, I performed single cell RNA-seq to compare ...


Exploiting Dna Repair And Er Stress Response Pathways To Induce Apoptosis In Glioblastoma Multiforme: A Dissertation, Jessica L. Weatherbee Aug 2016

Exploiting Dna Repair And Er Stress Response Pathways To Induce Apoptosis In Glioblastoma Multiforme: A Dissertation, Jessica L. Weatherbee

GSBS Dissertations and Theses

Glioblastoma multiforme (GBM) is a deadly grade IV brain tumor characterized by a heterogeneous population of cells that are drug resistant, aggressive, and infiltrative. The current standard of care, which has not changed in over a decade, only provides GBM patients with 12-14 months survival post diagnosis. We asked if the addition of a novel endoplasmic reticulum (ER) stress inducing agent, JLK1486, to the standard chemotherapy, temozolomide (TMZ), which induces DNA double strand breaks (DSBs), would enhance TMZ’s efficacy. Because GBMs rely on the ER to mitigate their hypoxic environment and DNA repair to fix TMZ induced DSBs, we ...


A Walk On The Fine Line Between Reward And Risk: Aav-Ifnβ Gene Therapy For Glioblastoma: A Dissertation, Dwijit Guhasarkar Jul 2016

A Walk On The Fine Line Between Reward And Risk: Aav-Ifnβ Gene Therapy For Glioblastoma: A Dissertation, Dwijit Guhasarkar

GSBS Dissertations and Theses

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. The current standard-of-care treatment including surgery, radiation and temozolomide (TMZ) chemotherapy does not prolong the survival satisfactorily. Here we have tested the feasibility, efficacy and safety of a potential gene therapy approach using AAV as gene delivery vehicle for treatment of GBM.

Interferon-beta (IFNβ) is a cytokine molecule also having pleiotropic anticancerous properties. Previously it has been shown by our group that AAV mediated local (intracranial) gene delivery of human IFNβ (hIFNβ) could be an effective treatment for non-invasive human glioblastoma (U87) in orthotopic xenograft mouse model.But ...


The Smurf2-Yy1-C-Myc Axis In The Germinal Center Reaction And Diffuse Large B Cell Lymphoma: A Dissertation, Sally E. Trabucco Jun 2016

The Smurf2-Yy1-C-Myc Axis In The Germinal Center Reaction And Diffuse Large B Cell Lymphoma: A Dissertation, Sally E. Trabucco

GSBS Dissertations and Theses

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin’s lymphoma. Patients who fail conventional therapy (~50%) have a poor prognosis and few treatment options. It is essential to understand the underlying biological processes, the progression of the disease, and utilize this information to develop new therapeutics.

DLBCL patients with high C-MYC expression have a poor prognosis and new therapeutics for these patients are needed. This thesis describes work testing the hypothesis that JQ1, which can indirectly inhibit C-MYC in some tumors, can be used as an effective treatment for DLBCL. Some tumors have an unknown mechanism causing ...


The Impact Of Mtorc2 Signaling On The Initiation And Progression Of Kras-Driven Pancreatic Neoplasias: A Dissertation, David R. Driscoll Mar 2016

The Impact Of Mtorc2 Signaling On The Initiation And Progression Of Kras-Driven Pancreatic Neoplasias: A Dissertation, David R. Driscoll

GSBS Dissertations and Theses

Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, develops through progression of premalignant pancreatic intraepithelial neoplasias (PanINs). In mouse-models, KRAS-activation in acinar cells induced an acinar-to-ductal metaplasia (ADM), and mutation of the Kras oncogene is believed to initiate PanIN formation. ADM is also promoted by pancreatic injury, which cooperates with activated KRAS to stimulate PanIN and PDAC formation from metaplastic ducts.

Our lab, and others, have shown that the downstream PI3K/AKT pathway is important for KRAS-mediated proliferation and survival in vitro and in vivo. Prior studies have demonstrated that full activation of AKT requires both PDK1- ...


Characterization Of Higher-Order Chromatin Structure In Bone Differentiation And Breast Cancer: A Dissertation, Ahmet Rasim Barutcu Feb 2016

Characterization Of Higher-Order Chromatin Structure In Bone Differentiation And Breast Cancer: A Dissertation, Ahmet Rasim Barutcu

GSBS Dissertations and Theses

Higher-order genome organization is important for the regulation of gene expression by bringing different cis-regulatory elements and promoters in proximity. The establishment and maintenance of long-range chromatin interactions occur in response to cellular and environmental cues with the binding of transcription factors and chromatin modifiers. Understanding the organization of the nucleus in differentiation and cancer has been a long standing challenge and is still not well-understood. In this thesis, I explore the dynamic changes in the higher-order chromatin structure in bone differentiation and breast cancer. First, we show dynamic chromatin contact between a distal regulatory element and the promoter of ...


Function Of The Β4 Integrin In Cancer Stem Cells And Tumor Formation In Breast Cancer: A Masters Thesis, Huayan Sun Jan 2016

Function Of The Β4 Integrin In Cancer Stem Cells And Tumor Formation In Breast Cancer: A Masters Thesis, Huayan Sun

GSBS Dissertations and Theses

The integrin α6β4 (referred to as β4) is expressed in epithelial cells where it functions as a laminin receptor. Integrin β4 is important for the organization and maintenance of epithelial architecture in normal cells. Particularly, β4 is shown to be essential for mammary gland development during embryogenesis. Integrin β4 also plays important roles in tumor formation, invasion and metastasis in breast cancer. However, the mechanism of how integrin β4 mediates breast tumor formation has not been settled. A few studies suggest that integrin β4 is involved in cancer stem cells (CSCs), but the mechanism is not clear. To address this ...


Insights Into Melanocyte Regeneration And Melanoma Initiation Using The Zebrafish Model System: A Dissertation, Sharanya Iyengar Oct 2015

Insights Into Melanocyte Regeneration And Melanoma Initiation Using The Zebrafish Model System: A Dissertation, Sharanya Iyengar

GSBS Dissertations and Theses

During regeneration, cells must coordinate proliferation and differentiation to rebuild tissues that are lost. Understanding how source cells execute the regeneration process has been a longstanding goal in regenerative biology with implications in wound healing and cell replacement therapies. Melanocytes are pigment-producing cells in the skin of vertebrates that can be lost during hair graying, injury and disease-related depigmentation. Melanoma is an aggressive skin cancer that develops from melanocytes, and it is hypothesized that melanoma cells have properties that are similar to melanocyte stem cells.

To gain insight into melanocyte regeneration we set out to identify the source of regeneration ...


Exploring New Strategies To Overcome Resistance In Glioblastoma Multiforme: A Dissertation, Yulian P. Ellis Aug 2015

Exploring New Strategies To Overcome Resistance In Glioblastoma Multiforme: A Dissertation, Yulian P. Ellis

GSBS Dissertations and Theses

Glioblastoma multiforme (GBM) tumors are highly malignant in nature and despite an aggressive therapy regimen, long–term survival for glioma patients is uncommon as cells with intrinsic or acquired resistance to treatment repopulate the tumor. This creates the need to investigate new therapies for enhancing GBM treatment outside of the standard of care, which includes Temozolomide (TMZ). Our lab focused on two novel strategies to overcome resistance in GBMs. In our first approach, the cellular responses of GBM cell lines to two new TMZ analogues, DP68 and DP86, are reported. The efficacy of these compounds was independent of DNA repair ...


Sentinel Lymph Node Biopsy In Elderly Patients With Intermediate Thickness Melanoma: A Masters Thesis, Kate H. Dinh May 2015

Sentinel Lymph Node Biopsy In Elderly Patients With Intermediate Thickness Melanoma: A Masters Thesis, Kate H. Dinh

GSBS Dissertations and Theses

Background: A landmark study suggested that wide excision of intermediate-thickness melanoma with sentinel lymph node biopsy (SLNB) and subsequent completion lymph node dissection (CLND) for regional disease may improve prognostication and disease-free survival (DFS) compared with those undergoing wide excision alone. However, these benefits were relatively small and not associated with an improvement in disease-specific survival (DSS). It remains unknown if SLNB and subsequent treatments are beneficial in elderly patients who have a decreased overall (OS) due to other causes.

Methods: Adults ≥ 70 years of age, who underwent surgical intervention for intermediate-thickness cutaneous melanoma from 2000-2013 were identified from a ...


Subtle Controllers: Micrornas Drive Pancreatic Tumorigenesis And Progression: A Dissertation, Brian J. Quattrochi Apr 2015

Subtle Controllers: Micrornas Drive Pancreatic Tumorigenesis And Progression: A Dissertation, Brian J. Quattrochi

GSBS Dissertations and Theses

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies in the United States, with an average five-year survival rate of just 6.7%. One unifying aspect of PDAC is mutational activation of the KRAS oncogene, which occurs in over 90% of PDAC. Therefore, inhibiting KRAS function is likely an effective therapeutic strategy for this disease, and current research in our lab and others is focused on identifying downstream effectors of KRAS signaling that may be therapeutic targets. miRNAs are powerful regulators of gene expression that can behave as oncogenes or tumor suppressors. Dysregulation of miRNA expression is commonly observed ...


Use Of Opioids For Pain Management In Nursing Homes: A Dissertation, Camilla B. Pimentel Apr 2015

Use Of Opioids For Pain Management In Nursing Homes: A Dissertation, Camilla B. Pimentel

GSBS Dissertations and Theses

Nursing homes are an essential yet understudied provider of cancer-related care for those with complex health needs. Nine percent of nursing home residents have a cancer diagnosis at admission, and it is estimated that one-third of them experience pain on a daily basis. Although pain management is an essential component of disease treatment, few studies have evaluated analgesic medication use among adults with cancer in this setting. Use of opioids, which are the mainstay of pain management in older adults because of their effectiveness in controlling moderate to severe pain, may be significantly related to coverage by the Medicare Part ...


Predicting Other Cause Mortality Risk For Older Men With Localized Prostate Cancer: A Dissertation, Daniel M. Frendl Mar 2015

Predicting Other Cause Mortality Risk For Older Men With Localized Prostate Cancer: A Dissertation, Daniel M. Frendl

GSBS Dissertations and Theses

Background: Overtreatment of localized prostate cancer (PCa) is a concern as many men die of other causes prior to experiencing a treatment benefit. This dissertation characterizes the need for assessing other cause mortality (OCM) risk in older men with PCa and informs efforts to identify patients most likely to benefit from definitive PCa treatment.

Methods: Using the linked Surveillance Epidemiology and End Results-Medicare Health Outcomes Survey database, 2,931 men (mean age=75) newly diagnosed with clinical stage T1a-T3a PCa from 1998-2009 were identified. Survival analysis methods were used to compare observed 10-year OCM by primary treatment type. Age and ...


Function And Regulation Of The Α6 Integrins In Mammary Epithelial Biology And Breast Cancer: A Dissertation, Cheng Chang Feb 2015

Function And Regulation Of The Α6 Integrins In Mammary Epithelial Biology And Breast Cancer: A Dissertation, Cheng Chang

GSBS Dissertations and Theses

Integrins have the ability to impact major aspects of epithelial biology including adhesion, migration, invasion, signaling and differentiation, as well as the formation and progression of cancer (Hynes 2002; Srichai and Zent 2010; Anderson et al. 2014). This thesis focuses on how integrins are regulated and function in the context of mammary epithelial biology and breast cancer with a specific focus on the α6 integrin heterodimers (α6β1 and α6β4). These integrins function primarily as receptors for the laminin family of extracellular matrix (ECM) proteins and they have been implicated in mammary gland biology and breast cancer (Friedrichs et al. 1995 ...


Autophagy-Independent Role For Beclin 1 In The Regulation Of Growth Factor Receptor Signaling: A Dissertation, Rasika Rohatgi Jan 2015

Autophagy-Independent Role For Beclin 1 In The Regulation Of Growth Factor Receptor Signaling: A Dissertation, Rasika Rohatgi

GSBS Dissertations and Theses

Beclin 1 is a haplo-insufficient tumor suppressor that is decreased in many human tumors. The function of Beclin 1 in cancer has been attributed primarily to its role in the degradative process of autophagy. However, the role of autophagy itself in tumorigenesis is context-dependent and can be both preventive and promoting. Due to its dual function in cancer a better understanding of this process is necessary to develop potential novel cancer therapies. To gain insight into the role of autophagy in breast carcinoma, I analyzed the autophagydependency of different subtypes of breast cancer. My results implicate that triple-negative breast carcinoma ...


Gli-Ikbke Requirement In Kras-Induced Pancreatic Tumorigenesis: A Dissertation, Mihir S. Rajurkar Nov 2014

Gli-Ikbke Requirement In Kras-Induced Pancreatic Tumorigenesis: A Dissertation, Mihir S. Rajurkar

GSBS Dissertations and Theses

Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive human malignancies, is thought to be initiated by KRAS activation. Here, we find that transcriptional activation mediated by the GLI family of transcription factors, although dispensable for pancreatic development, is required for KRAS induced pancreatic transformation. Inhibition of GLI using a dominant-negative repressor (Gli3T) inhibits formation of precursor Pancreatic Intraepithelial Neoplasia (PanIN) lesions in mice, and significantly extends survival in a mouse model of PDAC. Further, ectopic activation of the GLI1/2 transcription factors in mouse pancreas accelerates KRAS driven tumor formation and reduces survival, underscoring the importance of GLI transcription ...


Oncogene Function In Pre-Leukemia Stage Of Inv(16) Acute Myeloid Leukemia: A Dissertation, Liting Xue Oct 2014

Oncogene Function In Pre-Leukemia Stage Of Inv(16) Acute Myeloid Leukemia: A Dissertation, Liting Xue

GSBS Dissertations and Theses

The CBFbeta-SMMHC fusion protein is expressed in acute myeloid leukemia (AML) samples with the chromosome inversion inv(16)(p13;q22). This fusion protein binds the transcription factor RUNX with higher affinity than its physiological partner CBFbeta and disrupts the core binding factor (CBF) activity in hematopoietic stem and progenitor cells. Studies in the Castilla laboratory have shown that CBFbeta-SMMHC expression blocks differentiation of hematopoietic progenitors, creating a pre-leukemic progenitor that progresses to AML in cooperation with other mutations. However, the combined function of cumulative cooperating mutations in the pre-leukemic progenitor cells that enhance their expansion to induce leukemia is not ...


Identification And Characteristics Of Factors Regulating Hepatocellular Carcinoma Progression And Metastasis: A Dissertation, Leanne G. Ahronian Mar 2014

Identification And Characteristics Of Factors Regulating Hepatocellular Carcinoma Progression And Metastasis: A Dissertation, Leanne G. Ahronian

GSBS Dissertations and Theses

Hepatocellular carcinoma (HCC) is a common malignancy of the liver that is one of the most frequent causes of cancer-related death in the world. Surgical resection and liver transplantation are the only curative options for HCC, and tumor invasion and metastasis render many patients ineligible for these treatments. Identification of the mechanisms that contribute to invasive and metastatic disease may enlighten therapeutic strategies for those not eligible for surgical treatments. In this dissertation, I describe two sets of experiments to elucidate mechanisms underlying HCC dissemination, involving the activities of Krüppel-like factor 6 and a particular p53 point mutation, R172H.

Gene ...


Mdm2-P53 Signaling In Tissue Homeostasis And The Dna Damage Response: A Dissertation, Hugh S. Gannon Jun 2012

Mdm2-P53 Signaling In Tissue Homeostasis And The Dna Damage Response: A Dissertation, Hugh S. Gannon

GSBS Dissertations and Theses

The p53 transcription factor responds to various cellular stressors by regulating the expression of numerous target genes involved in cellular processes such as cell cycle arrest, apoptosis, and senescence. As these downstream pathways are harmful to the growth and development of normal cells when prolonged or deregulated, p53 activity needs to be under tight regulatory control. The Mdm2 oncoprotein is the chief negative regulator of p53, and many mouse models have demonstrated that absence of Mdm2 expression leads to constitutive p53 activation in a variety of cell types. While unregulated p53 can be deleterious to cells, functional p53 is essential ...


Slow-Cycling Cancer Cells: A Dissertation, Nathan F. Moore Jun 2012

Slow-Cycling Cancer Cells: A Dissertation, Nathan F. Moore

GSBS Dissertations and Theses

Tumor recurrence after chemotherapy is a major cause of patient morbidity and mortality. Recurrences are thought to be due to small subsets of stem-like cancer cells that are able to survive chemotherapy and drive tumor re-growth. A more complete understanding of stem-like cancer cell regulation is required to develop therapies to better target and eliminate these cells.

Slow-cycling stem cells are integral components of adult epithelial tissues and may give rise to cancer stem cell populations that share similar characteristics. These slow-cycling adult stem cells are inherently resistant to traditional forms of chemotherapy and transference of this characteristic may help ...


Antagonistic Pleiotropy: The Role Of Smurf2 In Cancer And Aging: A Dissertation, Charusheila Ramkumar Jun 2012

Antagonistic Pleiotropy: The Role Of Smurf2 In Cancer And Aging: A Dissertation, Charusheila Ramkumar

GSBS Dissertations and Theses

In response to telomere shortening, oxidative stress, DNA damage or aberrant activation of oncogenes, normal somatic cells exit the cell cycle and enter an irreversible growth arrest termed senescence. The limited proliferative capacity imposed by senescence on cells impedes the accumulation of mutations necessary for tumorigenesis and prevents proliferation of cells at risk of neoplastic transformation. Opposite to the tumor suppressor function, accumulation of senescent cells in adult organisms is thought to contribute to aging by depleting the renewal capacity of tissues and stem/progenitor cells, and by interfering with tissue homeostasis and functions. The Antagonistic Pleiotropy Theory of senescence ...


Mechanisms Of Kras-Mediated Pancreatic Tumor Formation And Progression: A Dissertation, Victoria A. Appleman May 2012

Mechanisms Of Kras-Mediated Pancreatic Tumor Formation And Progression: A Dissertation, Victoria A. Appleman

GSBS Dissertations and Theses

Pancreatic cancer is the 4th leading cause of cancer related death in the United States with a median survival time of less than 6 months. Pancreatic ductal adenocarcinoma (PDAC) accounts for greater than 85% of all pancreatic cancers, and is marked by early and frequent mutation of the KRAS oncogene, with activating KRAS mutations present in over 90% of PDAC. To date, though, targeting activated KRAS for cancer treatment has been very difficult, and targeted therapies are currently being sought for the downstream effectors of activated KRAS. Activation of KRAS stimulates multiple signaling pathways, including the MEK-ERK and PI3K-AKT signaling ...


Runx1 C-Terminal Domains During Hematopoietic Development And Leukemogenesis: A Dissertation, Christopher R. Dowdy May 2012

Runx1 C-Terminal Domains During Hematopoietic Development And Leukemogenesis: A Dissertation, Christopher R. Dowdy

GSBS Dissertations and Theses

Runx1 is a master regulator of hematopoiesis, required for the initiation of definitive hematopoiesis in the embryo and essential for appropriate differentiation of many hematopoietic lineages in the adult. The roles of Runx1 in normal hematopoiesis are juxtaposed with the high frequency of Runx1 mutations and translocations in leukemia. Leukemia associated Runx1 mutations that retain DNA-binding ability have truncations or frame shifts that lose C-terminal domains. These domains are important for subnuclear localization of Runx1 and protein interactions with co-factors. The majority of leukemia associated Runx1 translocations also replace the C-terminus of Runx1 with chimeric fusion proteins. The common loss ...


The Molecular Mechanisms For Maintenance Of Cancer Stem Cells In Chronic Myeloid Leukemia: A Dissertation, Haojian Zhang May 2012

The Molecular Mechanisms For Maintenance Of Cancer Stem Cells In Chronic Myeloid Leukemia: A Dissertation, Haojian Zhang

GSBS Dissertations and Theses

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder associated with the Philadelphia chromosome (Ph) that arises from a reciprocal translocation between chromosomes 9 and 22, thereby resulting in the formation of the chimeric BCR-ABL oncogene encoding a constitutively activated tyrosine kinase. BCR-ABL tyrosine kinase inhibitors (TKIs) induce a complete hematologic and cytogenetic response in the majority of chronic phrase CML patients. However, TKIs cannot efficiently eradicate leukemia stem cells (LSCs) because of the insensitivity of LSCs to TKIs. Therefore, developing new strategies to target LSCs is necessary and critical for curing CML, and success of this approach ...


Genetic Approaches To Study Transcriptional Activation And Tumor Suppression: A Dissertation, Ling Lin May 2012

Genetic Approaches To Study Transcriptional Activation And Tumor Suppression: A Dissertation, Ling Lin

GSBS Dissertations and Theses

The development of methods and techniques is the driving force of scientific research. In this work, we described two large-scale screens in studying transcriptional activation and tumor suppression.

In Part I, we studied transcriptional activation mechanisms by deriving and characterizing activation defective mutants. Promoter-specific transcriptional activators stimulate transcription through direct interactions with one or more components of the transcription machinery, termed the “target.” The identification of direct in vivo targets of activators has been a major challenge. We perform a large-scale genetic screen to derive and characterize tra1 alleles that are selectively defective for interaction with Gal4 in vivo. Utilizing ...


Analysis Of Integrin Α6Β4 Function In Breast Carcinoma: A Dissertation, Kristin D. Gerson Apr 2012

Analysis Of Integrin Α6Β4 Function In Breast Carcinoma: A Dissertation, Kristin D. Gerson

GSBS Dissertations and Theses

The development and survival of multicellular organisms depends upon the ability of cells to move. Embryogenesis, immune surveillance, wound healing, and metastatic disease are all processes that necessitate effective cellular locomotion. Central to the process of cell motility is the family of integrins, transmembrane cell surface receptors that mediate stable adhesions between cells and their extracellular environment. Many human diseases are associated with aberrant integrin function. Carcinoma cells in particular can hijack integrins, harnessing their mechanical and signaling potential to propagate cell invasion and metastatic disease, one example being integrin α6β4. This integrin, often referred to simply as β4, is ...


Localization Of Insulin Receptor Substrate-2 In Breast Cancer: A Dissertation, Jennifer L. Clark Mar 2012

Localization Of Insulin Receptor Substrate-2 In Breast Cancer: A Dissertation, Jennifer L. Clark

GSBS Dissertations and Theses

The insulin-like growth factor-1 receptor (IGF-1R) and many of its downstream signaling components have long been implicated in tumor progression and resistance to therapy. The insulin receptor substrate-1 (IRS-1) and IRS-2 adaptor proteins are two of the major downstream signaling intermediates of the IGF-1R. Despite their considerable homology, previous work in our lab and others has shown that IRS-1 and IRS-2 play divergent roles in breast cancer cells. Signaling through IRS-1 promotes cell proliferation, whereas signaling through IRS-2 promotes cell motility and invasion, as well as glycolysis. Moreover, using a mouse model of mammary tumorigenesis, our lab demonstrated that IRS-2 ...


Control Of Bovine Papillomavirus E2 Function By Acetylation And The Novel E2 Interacting Protein Rint1: A Dissertation, Edward J. Quinlan Jan 2012

Control Of Bovine Papillomavirus E2 Function By Acetylation And The Novel E2 Interacting Protein Rint1: A Dissertation, Edward J. Quinlan

GSBS Dissertations and Theses

Human papillomavirus infection is the cause of more than 99% of cervical cancer cases. The current vaccine is ineffective therapeutically; highlighting the need for continued papillomavirus research. One avenue that could be explored in this regard is the function of the papillomavirus E2 regulatory proteins. HPV E2 represses expression of the viral E6 and E7 oncoproteins. Reintroduction of E2 into cervical carcinoma cells results in growth arrest and cellular senescence. Understanding the mechanism of how E2 regulates the early promoter may be key to developing new therapeutic and prophylactic vaccines. Here, we describe regulation of E2 through acetylation and possibly ...