Cancer Biology Commons^™

Clinical And Pathologic Significance Of Integrin Α6Β4 Expression In Human Malignancies, Rachel L. Stewart

Theses and Dissertations--Clinical and Translational Science

Integrins are cellular adhesion molecules that bind cells to the extracellular matrix. The integrin α6β4, a receptor for laminins, is predominantly expressed on epithelial cells where it is present at the basal surface adjacent to the basement membrane. This integrin plays a critical role in maintaining normal cellular functions, yet has also been implicated in promoting invasion and metastasis in human malignancies. While overexpression of the integrin α6β4 has been detected in select human cancers, the clinical significance of integrin α6β4 expression in a number of malignancies has not been determined. The purpose of this study was to examine integrin …

The Influence Of Matrix Stiffness On Extracellular Matrix Protein Expression In 3d Encapsulated Mammary Fibroblasts, Kathryn Woods

PCOM Biomedical Studies Student Scholarship

A disease that transcends all races is breast cancer, the second leading cause of death among women with cancer. One factor, which participates in breast tumor progression, is the extracellular matrix (ECM), an acellular, protein-rich entity, which drives several cell, processes shown to promote tumorigenesis. Specifically, abnormal expression patterns and cross-linking of matrix fibers induces a more dense tissue structure, which has been reported to drive breast cancer progression. Alterations in ECM expression and cross-linking are in part due to carcinoma-associated fibroblasts (CAFs), activated fibroblasts which deposit copious ECM in the breast tumor environment. The goal of this study is …

Effect Of Adjuvant And Neoadjuvant Anti-Telomerase With Anthracycline Based Chemotherapy On Triple Negative Breast Cancer Cells, Luke T. Pardy

Student Summer Scholars Manuscripts

Breast cancer is the second leading cause of cancer related death in women in the US. In addition, 20% of all breast cancer cases in the U.S. are from the subtype known as Triple-Negative Breast Cancer (TNBC), which is the most aggressive and invasive form of the disease. This type of breast cancer has the worst prognosis, a decreased survival rate, and no targeted therapy. Over the decades, interest in pre- (Neoadjuvant) and post- (Adjuvant) chemotherapy treatments, in the management of TNBC has increased. Therefore, we evaluated the Adjuvant and Neoadjuvant effects of anti-telomerases (BIBR 1532 and GV6) with anthracycline-based …

Rheb Dynamics On Lysosomal Membranes Determines Mtorc1 Activity After Loss Of P53 Or Activation Of Ampk, Catherine M. Bell

Theses and Dissertations

The tumor suppressor TP53 is the most frequently altered gene in human cancers. The growth-promoting complex, mTORC1 plays a part of the oncogenic profile caused by dysfunctional p53. mTORC1 sits downstream of AMPK and other crucial tumor suppressors/oncogenes, PTEN, LKB1, and Akt. The antifolate pemetrexed was found by this laboratory to activate AMPK via the inhibition of the enzyme AICART in de novo purine synthesis. This work presents a mechanism of mTORC1 activation with p53 loss, as well as of mTORC1 inhibition by pemetrexed-induced AMPK. We have found that mTORC1 activity was substantially upregulated by the loss …

Immunotherapy Of Cancer: Reprogramming Tumor/Immune Cellular Crosstalk To Improve Anti-Tumor Efficacy, Kyle K. Payne

Theses and Dissertations

Immunotherapy of cancer has been shown to be promising in prolonging patient survival. However, complete elimination of cancer and life-long relapse-free survival remain to be major challenge for anti-cancer therapeutics. We have previously reported that ex vivo reprogramming of tumor-sensitized immune cells by bryostatin 1/ionomycin (B/I) and the gamma-chain (γ-c) cytokines IL-2, IL-7, and IL-15 resulted in the generation of memory T cells as well as CD25+ NKT cells and CD25+ NK cells. Adoptive cellular therapy (ACT) utilizing these reprogrammed immune cells protected FVBN202 mice from tumor challenge, and overcame the suppressive functions of myeloid-derived suppressor cells (MDSCs). We then …

The Role Of Srsf3 In Control Of Alternative Splicing Of Cpeb2 In Triple Negative Breast Cancer, Brian P. Griffin

Theses and Dissertations

In the presented study, we identified that SRSF3 controls the alternative splicing of CPEB2 and consequently promotes a metastatic phenotype in triple negative breast cancer (TNBC). TNBC causes thousands of deaths annually, frequently due to a lack of effective treatments and a high rate of metastasis in patients. Alternative splicing has been found to be dysregulated in numerous cancers, while splicing factors such as SRSF3 are variably expressed. In this study we performed a siRNA panel to screen potential splicing factors, then used specific siRNA to study the effect of its knockdown on cellular function. These results showed that SRSF3 …

Pemetrexed, A Modulator Of Amp-Activated Kinase Signaling And An Inhibitor Of Wild Type And Mutant P53, Stuti Agarwal

Theses and Dissertations

New drug discoveries and new approaches towards diagnosis and treatment have improved cancer therapeutics remarkably. One of the most influential and effective discoveries in the field of cancer therapeutics was antimetabolites, such as the antifolates. The interest in antifolates increased as some of the antifolates showed responses in cancers, such as mesothelioma, leukemia, and breast cancers. When pemetrexed (PTX) was discovered, our laboratory had established that the primary mechanism of action of pemetrexed is to inhibit thymidylate 22 synthase (TS) (E. Taylor et al., 1992). Preclinical studies have shown that PTX has a broad range of antitumor activity in human …

Interaction Between Atm Kinase And P53 In Determining Glioma Radiosensitivity, Syed F. Ahmad

Theses and Dissertations

Glioblastoma multiforme (GBM) is the most common primary brain tumor. Studies have shown that targeting the DNA damage response can sensitize cancer cells to DNA damaging agents. Ataxia telangiectasia mutated (ATM) is involved in signaling DNA double strand breaks. Our group has previously shown that ATM inhibitors (ATMi) sensitize GBM cells and tumors to ionizing radiation. This effect is greater when the tumor suppressor p53 is mutated.

The goals of this work include validation of a new ATM inhibitor, AZ32, and elucidation of how ATMi and p53 status interact to promote cell death after radiation. We propose that ATMi and …

Nitric Oxide Synthase Activity And Its Modulation In The Treatment Of Colorectal Cancer, Asim Alam

Theses and Dissertations

The American Cancer Society estimates more than 141,000 new cases of and about 50,000 deaths from colorectal cancer every year. Treatment options include surgery, radiation therapy and targeted therapies such as anti-angiogenics. However, no therapies address the key driving factor of colorectal cancer: inflammation. It is well known that chronic inflammatory conditions such as Crohn’s Disease, ulcerative colitis, diabetes, obesity and cigarette smoking all elevate the risk of developing colorectal cancer. One of the hallmarks of chronic inflammation is the elevated levels of reactive oxygen/nitrogen species (ROS/RNS). A primary source of these ROS/RNS is uncoupled Nitric Oxide Synthase (NOS). Under …

The Role Of Brct-Containing Proteins Brca1 And Paxip1 In Cancer, Ankita Jhuraney

USF Tampa Graduate Theses and Dissertations

Modular domains of proteins are important in cellular signaling processes. Eukaryotic cells are constantly undergoing DNA damage due to exogenous and endogenous sources of damage. The DNA damage response (DDR) involves a complex network of signaling events mediated by modular domains such as the BRCT (BRCA1 C-terminal) domains. Therefore, proteins containing BRCT domains are important for DNA damage detection and signaling. In this dissertation, we focus on two BRCT-containing proteins BRCA1 and PAXIP1. BRCA1 is a gene that is known to be associated with increased risk of hereditary breast and ovarian cancer. Germline variants of BRCA1 are assessed to determine …

Targeting T-Bet For Prevention Of Graft-Versus-Host Disease And Leukemia Relapse After Allogeneic Hematopoietic Stem Cell Transplantation, Jianing Fu

USF Tampa Graduate Theses and Dissertations

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapeutic option for many malignant diseases. However, the efficacy of allo-HSCT is limited by the occurrence of destructive graft-versus-host disease (GVHD). Since allogeneic T cells are the driving force in the development of GVHD, their activation, proliferation, and differentiation are key factors to understanding GVHD pathogenesis. On the other hand, antigen-presenting cells (APCs) are essential for allogeneic T-cell priming and the development of GVHD. The T-box transcription factor T-bet is a master regulator for IFN-γ production and Th1 differentiation. T-bet also regulates the functions of APCs including dendritic cells (DCs) and …

Dancing Through Life: Allosteric Transitions And Structural Analysis Of Hsp70 And Hsp110 Chaperone Proteins, Gabrielle Stetz, Gennady M. Verkhivker

Student Scholar Symposium Abstracts and Posters

The molecular chaperone protein Hsp70 is centrally involved in cellular homeostasis by assisting in the folding and degradation of protein substrates. Hsp70 is joined by co-chaperones, such as Hsp110, which contribute to specialized tasks of the Hsp70 complex. Imbalances of this heat shock protein system are believed to be involved with the deregulation of cancer pathways and other human diseases. Better understanding of how these heat shock proteins work at the molecular level, which has been investigated using molecular docking tools, will give more clues about biological function. Simulating the formation and function of Hsp70 based chaperone complexes could provide …

Engineered Plga Nanoparticles For Delivery Of Sirna In Mcf-7 Breast Cancer Cells, Sydney Pong, Samit Shah, Vivek Gupta

Student Scholar Symposium Abstracts and Posters

Small interfering RNAs have been an emerging medical treatment for molecular based diseases as they are capable of gene-specific knockdown. Appropriate and efficient delivery remains one of the biggest challenges in the development of siRNA as an anti-cancer treatment. Nanoparticles containing siRNA were characterized and the efficacy of various peptides in the transfection of the nanoparticles were tested. A gene silencing assay was developed in order to determine the effect of siRNA therapeutics on gene functionality in breast cancer cells.

Assessment Of The Effects Of Caffeine, Gallic Acid, And Epigallocatechin-3-Gallate On Cell Inhibition, Pim-3 And E. Cadherin Protein Levels In Two Lines Of Pancreatic Cancer Cells, Lena Haddad, Melissa Rowland-Goldsmith

Student Scholar Symposium Abstracts and Posters

According to the American Cancer Society, pancreatic cancer is currently the fourth leading cause of cancer related deaths in the United States. In addition to being an exceptionally aggressive form of cancer, it is particularly difficult to treat because it is usually diagnosed in late stages after the onset of metastasis (1). Consequently, the current treatments used, including chemotherapy and radiation, have been rendered ineffective (2). As a result, focus has been placed on using dietary alternatives which are known to possess chemopreventive properties (3). Previous studies have indicated that Gallic acid (an important phytochemical in pomegranates) and Epigallocatechin-3-Gallate (the …

Toxicity And Cosmesis Outcomes For Single Fraction Intra-Operative Electron Radiotherapy (Ioert) For Breast Cancer, Monica Hanna, Robert Ash, Wesley Babaran, Michele M. Carpenter, Afshin Forouzannia, Jay K. Harness, Brian Kaltenecker, Snehith Maddula, Venita Williams, Lawrence Wagman

Student Scholar Symposium Abstracts and Posters

Background: Adjuvant radiation therapy is proven to reduce local recurrence in patients with early stage breast cancer. To reduce toxicity, improve geographic accuracy, and reduce treatment time, IOERT can be utilized as an alternative to external beam radiation therapy. The study’s objective was to determine the short term toxicity and cosmesis profile of single fraction IOERT given as definitive treatment in a community setting. Materials and Methods: From Mar 2012 to Jul 2014, 84 patients (3 bilateral), ages 45-91 y.o. with stage 0-II were treated with IOERT (Mobetron, IntraOp Medical, Sunnyvale, CA). A single 21 Gy fraction was administered to …

Molecular Insights Into Prostate Field Cancerization: Telomere Length, Egr-­‐1 Expression, And Regulation Of Mic-­‐1, Pdgf-­‐A, And Fas, Emily Frisch, Kristin Gabriel, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The diagnosis of prostate cancer (adenocarcinoma) relies on screening for elevated prostate-specific antigen (PSA) in blood samples and on digital rectal examination (DRE). With high PSA levels and/or abnormal DRE, physicians recommend a biopsy, which often misses the location of the adenocarcinoma and results in false negatives. Previous studies have shown expression of the key transcription factor early growth response 1 (EGR-1), the pro-survival factor macrophage inhibitor cytokine 1 (MIC-1), and the growth stimulatory platelet derived growth factor A (PDGF-A) to be up-regulated in histologically normal tissues 1 centimeter adjacent to prostate adenocarcinomas. We hypothesize that tumors emerge from “field …

Prostate Field Cancerization -- Thinking Outside The Tumor, Dor Shoshan, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

Prostate field cancerization (or field effect) is characterized by the presence of molecular alterations in histologically normal tissues adjacent to adenocarcinomas. Accordingly, our research indicates deregulated expression of several proteins that define this type of molecular pathology. The scope of the present study was to determine the expression of the key transcription factor and potential marker of field cancerization early growth response 1 (EGR-1) in human prostate tissues derived from prostatectomies and biopsy cores.

EGR-1 was detected by immunofluorescence using a polyclonal anti-human EGR-1 and Alexa Fluor 488-conjugated secondary antibodies. EGR-1 expression was quantitated by determining the pixel count per …

Novel Posttranslational Modification In Lkb1 Activation And Function, Szu-Wei Lee

Dissertations and Theses (Open Access)

Cancer cells display dramatic alterations in cellular metabolism to meet their needs of increased growth and proliferation. In the last decade, cancer research has brought these pathways into focus, and one emerging issue that has come to attention is that many oncogenes and tumor-suppressors are intimately linked to metabolic regulation (Jones and Thompson, 2009). One of the key tumor-suppressors involved in metabolism is Liver Kinase B1 (LKB1). LKB1 is the major upstream kinase of the evolutionarily conserved metabolic sensor—AMP-activated protein kinase (AMPK). Activation of the LKB1/AMPK pathway provides a survival advantage for cells under energy stress. LKB1 forms a heterotrimeric …

Lkb1 Deficient Non-Small Cell Lung Cancer Cells Are Vulnerable To Energy Stress Induced By Atp Depletion, Chao Yang

Dissertations and Theses (Open Access)

Lung cancer is the second most frequent cancer in United States, which represents about 13.5% of new cancer cases every year. It accounts for about 27.2% of all cancer related deaths, which is more than the sum of deaths caused by prancretic, breast and colorectal. On average, only about 16% of lung cancer patients survive beyond 5 years. LKB1 is the third most mutated gene in lung cancer. It has been shown that LKB1 is mutated in at least 15% to 30% of NSCLC. Tumor with LKB1 mutation is associated with poor differentiation, high metastasis and worse response to chemotherapy. …

Role Of Phosphorylation Of Focal Adhesion Kinase At Tyrosine 861 In Prostate Cancer Metastasis, Tanushree Chatterji

Dissertations and Theses (Open Access)

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that mediates interactions between the extracellular matrix and intracellular signaling pathways critical in promoting numerous cellular functions including adhesion, proliferation, survival and migration. Most FAK functions result from phosphorylation by Src family kinases, which trigger numerous signaling cascades. Overexpression of FAK is associated with metastasis in many solid tumors, including prostate cancer. Hence, understanding the mechanisms by which FAK is regulated in prostate cancer will better elucidate its role in prostate cancer metastasis. Work in this dissertation tested the hypothesis that altered phosphorylation of FAK is critical for cell migration and …