Cancer Biology Commons^™

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 …

Sustained Adrenergic Signaling Promotes Cervical Cancer Progression, Nouara C. Sadaoui

Dissertations and Theses (Open Access)

Background: Chronic stress and sustained adrenergic signaling are known to promote tumor progression. The underlying mechanisms behind this process are not well understood. We examined the effects of sustained adrenergic signaling on cervical cancer progression through increased expression of HPV oncogenes, E6 and E7.

Materials and Methods: ADRβ expression levels were examined in patient-derived cervical cancer samples. We used an orthotopic model of cervical cancer to investigate the effects of restraint stress on tumor growth and metastasis. We evaluated the in vivo effects of a β-blocker, propranolol, and HPV E6/E7 siRNA. In vitro, ADRβ positive cervical cancer cells were …

Mdm2-Mediated Degradation Of Sirt6 Phosphorylated By Akt1 Promotes Tumorigenesis And Trastuzumab Resistance In Breast Cancer, Umadevi Thirumurthi

Dissertations and Theses (Open Access)

Sirtuin6 (SIRT6) is one of the members of the Sirtuin family and functions as a longevity assurance gene by promoting genomic stability. It also regulates various cancer-associated pathways and was recently established as a bonafide tumor suppressor in colon cancer. This suggests that SIRT6 is an attractive target for pharmacological activation in cancer treatment, and hence, identification of potential regulators of SIRT6 would be an important and critical contribution towards cancer treatment. Here, we show that AKT1 phosphorylates SIRT6 at Ser³³⁸ and induces MDM2-SIRT6 interaction, priming SIRT6 for degradation via the MDM2-dependent ubiquitin-proteasome pathway. Blocking SIRT6 Ser³³⁸ phosphorylation …

Jab1 Negatively Regulates Pten And Promotes Resistance To Trastuzumab In Her2-Positive Breast Cancer, Thuy T. Vu

Dissertations and Theses (Open Access)

HER2-positive breast cancer, which is characterized by the over-expression of the HER2 onco-protein, accounts for approximately 20% of all breast cancer cases. Trastuzumab (Herceptin), the first targeted therapy approved for HER2-positive disease, potently prevents the activation of signaling pathways downstream of HER2 and significantly improves patients’ outcomes. However, resistance to trastuzumab is inevitable; such resistance can occur through reduced expression of PTEN protein.

Jab1 is over-expressed in 50% of primary cancers and 90% of metastatic tumors. Our lab previously showed that depletion of Jab1 in combination with trastuzumab treatment up-regulated PTEN in mouse xenografts refractory to trastuzumab. PTEN was not …

Epidermal Growth Factor Receptor Induces Fyn Expression Via Up-Regulation Of P47phox In Glioblastoma Multiforme, Blake P. Johnson

Dissertations and Theses (Open Access)

Src family kinases (SFKs) are commonly over-expressed and/or activated in glioblastoma multiforme (GBM), where they serve as key mediators of GBM cell proliferation, survival, invasion and angiogenesis. Mechanisms of allosteric SFK activation are well described; however, the SFK Fyn is commonly up-regulated at the mRNA level in multiple human cancers, including GBM, where the mode of increased expression is poorly understood. Since activating mutations in the epidermal growth factor receptor (EGFR) are commonly occurring in GBM, we examined whether EGFR could induce Fyn expression. Here, we found that wild-type EGFR, and to a greater extent hyper-activating EGFR mutants, EGFRΔIII and …

Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica Elizabeth Reyes

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are two highly aggressive breast cancer subtypes associated with a poor outcome. Despite sensitivity to current treatment, these breast cancers subtypes have a high recurrence rate and proclivity to metastasize early. The aggressiveness of IBC and TNBC have been linked to CSCs and epithelial to mesenchymal transition (EMT), which are critical features of breast cancer progression and metastasis. The clinical challenge faced in the treatment of IBC and TNBC is finding a treatment strategy to target the cancer stem-like (CSC) population to block metastasis. Cyclooxygenase-2 (COX-2) and receptor activator of nuclear …

Managing Devil Facial Tumour Disease In Tasmanian Devils (Sarcophilus Harrisii): An Investigation Of Heat Shock Proteins As Potential Vaccine Adjuvants, Monika Payerhin

Independent Study Project (ISP) Collection

The world’s largest carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii), is facing extinction from a deadly, highly communicable cancer that has already decimated over 85% of devil populations in the wild: devil facial tumour disease (DFTD). DFTD cells effectively evade recognition by the immune system, and every devil that contracts the disease dies from it. Many attempts have been made at developing a vaccine that could help save this now-threatened species. Heat shock proteins have been linked to enhanced immune recognition of pathogens, making them potential candidates for acting as adjuvants to such a vaccine against DFTD. In this study, …

Novel Biomarkers Can Be Used As Targets To Combat Cancer, Harini Krishnan

Graduate School of Biomedical Sciences Theses and Dissertations

Cancer kills almost 8 million people per year worldwide. Therefore, about 13 people die from cancer every minute. Clearly, current cancer treatments are not completely effective. Moreover, many chemotherapeutic reagents are not very specific for cancer cells.

These agents attack rapidly dividing cells, including a wide array of normal cells, in addition to cancer cells, in the body. This lack of specificity can cause collateral damage and significant side effects in patients. More targeted therapies are needed to successfully combat cancer. Specific cancer biomarkers need to identified and characterized in order to develop better targeted anti-cancer drugs.

Tumor cells can …

Novel Therapeutic Strategies In Lung Cancer, Courtney A. Kurtyka

USF Tampa Graduate Theses and Dissertations

Lung cancer is the leading cause of cancer-related death and the second most diagnosed cancer in the United States. Unfortunately, many patients either do not have any common mutations for which there are already targetable agents, or they eventually become resistant to these compounds. As such, there is a high demand for new, effective methods of treating this disease as well as predicting patient prognosis and potential benefit from chemotherapy. In this work, numerous strategies for treating lung cancer are explored.

The first method described here is through the use of a pan-early 2 factor (E2F) inhibitor, HLM006474, which is …

The Evolution Of Prostate Cancer Therapy: Targeting The Androgen Receptor (Ar), Jeanny B. Aragon-Ching

Medicine Faculty Publications

No abstract provided.

Enhanced Breast Cancer Therapy With Nspefs And Low Concentrations Of Gemcitabine, Shan Wu, Jinsong Guo, Wendong Wei, Jue Zhang, Jing Fang, Stephen J. Beebe

Bioelectrics Publications

Chemotherapy either before or after surgery is a common breast cancer treatment. Long-term, high dose treatments with chemotherapeutic drugs often result in undesirable side effects, frequent recurrences and resistances to therapy. The anti-cancer drug, gemcitabine (GEM) was used in combination with pulse power technology with nanosecond pulsed electric fields (nsPEFs) for treatment of human breast cancer cells in vitro. Two strategies include sensitizing mammary tumor cells with GEM before nsPEF treatment or sensitizing cells with nsPEFs before GEM treatment.Breast cancer cell lines MCF-7 and MDA-MB-231 were treated with 250 65 ns-duration pulses and electric fields of 15, 20 or 25 …

Mechanisms And Molecular Biology Of Major Tumor Suppressors, Brienne E. Engel

USF Tampa Graduate Theses and Dissertations

This dissertation is devoted to the study of the molecular biology of major tumor suppressors, defined as those that prevent the cellular processes identified as the hallmarks of cancer. Specifically, the major tumor suppressors pRb and STK11 are explored in the context of osteosarcoma and lung cancer, respectively.

RB1 was the first tumor suppressor gene discovered. Over four decades of work have revealed that the Rb protein (pRb) is a master regulator of biological pathways influencing virtually every aspect of intrinsic cell fate including cell growth, cell-cycle checkpoints, differentiation, senescence, self-renewal, replication, genomic stability and apoptosis. While these many processes …

The Effect Of Pomegranate Juice Extract On The Hedgehog Signaling Pathway In Pancreatic Cancer, Veronica Gomez, Talia Shackelford, Autumn Tocchi, Melissa Rowland-Goldsmith

e-Research: A Journal of Undergraduate Work

Pancreatic cancer is the fourth leading cause of cancer death in the United States. There have been several reports indicating that phytochemicals in fruits can reduce the risk of cancer due to the anti-oxidant and anti-inflammatory effects of the polyphenols. Our lab has shown that pomegranate juice extract (PJE) has anti-proliferative and pro-apoptotic effects in human pancreatic cancer cells. In the past, we have shown that cells adhere more strongly to the plate when treated with PJE. This observation prompted an investigation of how PJE regulates cell adhesion proteins. Previously, our lab investigated E-cadherin, a cell adhesion protein. Upon activation …

Sorting Reality From What We Think We Know About Breast Cancer In Africa, Sulma I. Mohammed, Joe B. Harford

Department of Comparative Pathobiology Faculty Publications

Much attention has been paid to the features of breast cancer in Africa and the parallels between breast cancer in indigenous Africans and in African American women, including a shift toward earlier onset; a tendency toward poorer outcomes; and an increased likelihood for the tumors to be negative for the estrogen receptor (ER), the progesterone receptor (PR), and/or the human epidermal growth factor receptor-2 (HER2) [1,2]. One of the more aggressive forms of breast cancer is termed ‘‘triple negative,’’ i.e., ER2, PR2, HER22 [3]. Patients with triple negative breast cancer tend to be younger than patients with other forms of …

Biological Activities Of Fusarochromanone: A Potent Anti-Cancer Agent, Elahe Mahdavian, Phillip Palyok, Steven Adelmund, Tara Williams-Hart, Brian D. Furmanski, Yoon-Jee Kim, Ying Gu, Mansoureh Barzegar, Yang Wu, Kaustubh N. Bhinge, Gopi K. Kolluru, Quincy A. Quick, Yong-Yu Liu, Christopher G. Kevil, Brian A. Salvatore, Shile Huang, John L. Clifford

Biology Faculty Research

Background

Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity.

Results

Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC₅₀ ranging from 10nM-2.5 μM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT …

Small Molecule Tyrosine Kinase Inhibitors Of Erbb2/Her2/Neu In The Treatment Of Aggressive Breast Cancer., Richard L. Schroeder, Cheryl L. Stevens, Jayalakshmi Sridhar

Faculty and Staff Publications

he human epidermal growth factor receptor 2 (HER2) is a member of the erbB class of tyrosine kinase receptors. These proteins are normally expressed at the surface of healthy cells and play critical roles in the signal transduction cascade in a myriad of biochemical pathways responsible for cell growth and differentiation. However, it is widely known that amplification and subsequent overexpression of the HER2 encoding oncogene results in unregulated cell proliferation in an aggressive form of breast cancer known as HER2-positive breast cancer. Existing therapies such as trastuzumab (Herceptin^®) and lapatinib (Tyverb/Tykerb^®), a monoclonal antibody inhibitor …

Robust Meta-Analysis Shows That Glioma Transcriptional Subtyping Complements Traditional Approaches, Sanghoon Lee, Stephen Piccolo, Kristina Allen-Brady

Faculty Publications

Background Gliomas traditionally have been sub-classified
based on histopathological observations. However, this ap-
proach is subject to inter-observer variability, and histopatho-
logical features may not reflect the biological mechanisms that
drive tumor growth. High-throughput transcriptional profiling
has shown promise in objectively and reproducibly identify-
ing glioma subtypes. Most prior studies have typically used
only modest sample sizes and have sometimes overlooked
important data-processing steps to ensure sample quality and
to evaluate the robustness of quantitative findings. The pur-
pose of our study was to define robust glioma subtypes by
applying rigorous preprocessing and validation steps to 1,952
microarray samples aggregated …

Poly(Arginine) Derived Cancer-Targeting Peptides For The Development Of A Cancer-Targeted Gene Therapy Approach In Hepg2 Liver Cancer Cells, Stesha C. Joseph

Seton Hall University Dissertations and Theses (ETDs)

Cancer is a disease that has eluded medicinal approaches for many years and as a result new and improved therapeutic approaches are in constant demand. Although chemotherapy and radiation treatments have assisted in suppressing the growth of tumors, their poor selectivity and efficacy are major limitations for effective therapy en route towards the development of a cure for the cancer epidemic. With the mission of conquering cancer at heart, researchers have pursued a new form of cancer therapy, aptly named, a cancer targeting approach. This method revolves around the selection of a suitable biomarker, typically a cell surface receptor …

The Role Of Ape/Ref-1 In Hepatocellular Carcinoma Progression, Zhen Yang, Sun Yang, Bobbye J. Misner, Feng Liu-Smith, Frank L. Meyskens

Pharmacy Faculty Articles and Research

Hepatocellular carcinoma (HCC) is responsible for a third of the estimated cancer-caused deaths worldwide. To deeply understand the mechanisms controlling HCC progression is of primary importance to develop new approaches for treatment. Apurinic/apyrimidinic endonuclease-1/redox effector factor 1 (APE/Ref-1) has been uncovered elevated in various types of cancer, including HCC. Additionally, HCC progression is always correlated with elevated copper (Cu). Our previous data demonstrated that Cu treatment initiated APE/Ref-1 expression and its downstream targets. Therefore, we hypothesized that APE/Ref-1 may be involved in HCC progression through mediating the effect of Cu to its signaling cascades. Following different treatments, human HCC cell …

Effects Of Leptin On Established Glioblastoma Cell Lines, Nicholas J. Cook

All NMU Master's Theses

Glioblastoma is one of the most difficult cancers to treat because it is aggressive and resistant to therapy. The discovery of new therapeutic targets is drastically needed as zero improved treatment options have been added to the standard of care over the past 15 years. New and promising therapeutic targets are arising from psychosocial and environmental enrichment studies examining the role of stress in cancer progression. In animal models, eustress appears to slow tumor growth and recurrence resulting in increased overall survival and progression free survival while distress is associated with decreased overall survival. The cellular pathways activated by eustress …

Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti

Dissertations and Theses (Open Access)

After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but …

Mapping The Human Vasculature By In Vivo Phage Display, Julianna Bronk

Dissertations and Theses (Open Access)

In vivo phage display screenings by intravenous injection of a random phage-displayed peptide library allow for the selection of peptides that localize to specific vascular beds. At the University of Texas MD Anderson Cancer Center, we have had the opportunity to perform phage display screenings in cancer patients in order to select for cancer specific targets directly in humans. These targets serve to define biochemical diversity of endothelial cell surfaces and can be validated and explored towards the design of vascular-targeted pharmacology. In the most recent patient screen, samples were recovered from hepatocellular carcinoma (HCC) as well as 26 additional …