Digital Commons Network^™

The Role Of Tumor Suppressor Co-Chaperone Chip/Stub1 In Erbb2-Mediated Oncogenesis, Haitao Luan

Theses & Dissertations

The epidermal growth factor receptor (EGFR) family member ErbB2 (Her2) is overexpressed in 20 -30% of invasive breast cancers and this overexpression correlates with poor prognosis and shorter overall as well as disease-free survival. Aberrant expression of ErbB2 through gene amplification, transcriptional deregulation and/or altered endocytic trafficking results in overexpression of ErbB2 at the plasma membrane and biases ErbB2 from primarily ligand-driven hetero-dimerization under normal expression conditions to increased ligand-independent homo-dimer and hetero-dimer formation and consequent activation. C-terminus of HSC70-Inteeracting protein (CHIP)/STIP1-homologous U-Box containing protein 1 (STUB1) is an HSP90/HSC70 interacting negative co-chaperone known to promote ubiquitination and degradation of …

Chronic Ethanol Exposure Enhances The Aggressiveness Of Breast Cancer: The Role Of P38Γ, Mei Xu, Siying Wang, Zhenhua Ren, Jacqueline A. Frank, Xiuwei H. Yang, Zhuo Zhang, Zun-Ji Ke, Xianglin Shi, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the …

Combined Systemic And Ocular Chemotherapy For Anterior Segment Metastasis Of Systemic Mantle Cell Lymphoma., Aniruddha Agarwal, Mohammad Ali Sadiq, William R. Rhoades, Loren S. Jack, Mostafa Hanout, Philip J. Bierman, William W. West, Quan Dong Nguyen

Journal Articles: Ophthalmology

BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin's lymphoma that rarely metastasizes to the iris and the anterior segment. Blastic/pleomorphic morphology is thought to have an adverse effect on prognosis in MCL. MCL is resistant to conventional chemotherapeutic regimens with a tendency for multiple relapses. Management of anterior segment metastasis of systemic MCL has not been described in literature.

FINDINGS: A 58-year-old male presented with an aggressive, relapsing, metastatic, systemic blastic variant of MCL with ocular involvement. At the time of initial presentation, large tumor cells were visible in the anterior chamber (AC) along with hypopyon and …

The Effects Of Ketorolac And Its Enantiomers On Breast Cancer Proliferation And Metastasis, Amanda Peretti

Biomedical Sciences ETDs

Breast cancer is the second leading cause of cancer related deaths in women. Advanced breast cancer can metastasize to the lungs, liver, bones and brain becoming fatal conditions for many patients. There is a dire need for metastasis preventing medications, however the process required for a medication to become FDA approved for clinical use is long and arduous. Studies have found promising benefits for breast cancer patients given ToradolTM, or racemic ketorolac, as an NSAID during resection surgery. However, long-term use of racemic ketorolac is not recommended. Currently FDA-approved for use in the racemic form, ketorolac has the potential to …

Characterization Of Erbb4 Expression In Osteosarcoma, Nupur Lala

Dissertations & Theses (Open Access)

ERBB4 (Her-4) is a member of the ERBB family of Class I receptor tyrosine kinases. ERBB4 is unique within the ERBB family for alternate splicing in its juxtamembrane and cytoplasmic regions, which produces four juxtamembrane isoforms and two cytoplasmic isoforms. The cleavable juxtamembrane isoforms, Jm-a and Jm-d, can undergo proteolytic cleavage and produce an 80-kDa cytoplasmic fragment referred to as “p80,” which has been demonstrated to enhance cellular survival and malignant behavior in many solid tumors [44]. ERBB4 was almost exclusively 80 kDa in size and localized to the nucleus in primary tumors and metastases in studies characterizing ERBB4 expression …

P27 Drives Pi3k-Dependent Cancer Metastasis By Activating Emt Transcription Factors To Induce An Emt Program, Alexandra Besser

Open Access Dissertations

In normal cells, p27 regulates cell cycle and functions as an atypical tumor suppressor. Unlike typical tumor suppressors such as p16 and pRb, p27 gene deletions or mutations are rarely observed in human cancers. Instead, p27 is deregulated through either excess degradation or through key C-terminal phosphorylations, in human cancers. Phosphorylation at T157 or T198 by different PI3K effector kinases allows p27 to take on new binding partners and promote oncogenic transformation. This thesis addresses the functional contribution of T157 and T198-phosphorylated, deregulated p27 to cancer progression and metastasis. By studying the effects of a transfected cell cycle defective (CK-) …

The Role Of Endothelin 3 In Melanoma Progression And Metastasis, Nikeisha L. Chin

FIU Electronic Theses and Dissertations

Endothelin receptor b (Ednrb) and its ligand Endothelin 3 (Edn3) have been implicated in melanoma. Several studies have shown an upregulation of EDNRB and EDN3 at both the protein and mRNA levels, as melanoma becomes more aggressive. This study investigated the putative role played by Edn3 over-expression in melanoma progression and angiogenesis in vivo. We crossed Tg(Grm1)Epv transgenic mice that aberrantly express metabotropic glutamate receptor1 under the Dopachrome tautomerase promoter, leading to spontaneous melanocytic lesions in the ears and tails that do not metastasize, with transgenics that overexpress Edn3 under the Keratin 5 promoter ( …

Function Of Long Noncoding Rnas In Breast Cancer, Edward J. Richards

USF Tampa Graduate Theses and Dissertations

Breast cancer is a disease that will be diagnosed in about 1 in 10 women throughout their lifetime. The majority of breast cancers are originated from the epithelial cells of the mammary ducts, and this occurrence can be due to several factors including hereditary and acquired mutation. There are several major breast cancer subtypes, including estrogen receptor-α (ERα)-positive, HER2-enriched and triple-negative (TNBC). Patients diagnosed with ER+ tumors are generally treated with estrogen blockers (e.g., tamoxifen, letrozole and fulvestrant). Patients with HER2+ tumors are commonly administered with drugs that block HER2 signaling (e.g., trastuzumab) or inhibit HER2’s tyrosine kinase activity (e.g., …

Clinical And Experimental Importance Of Circulating Tumor Cells In Prostate Cancer, Lori Lowes

Electronic Thesis and Dissertation Repository

Prostate cancer (PCa) remains a leading cause of death in men, primarily due to ineffective treatment in the metastatic setting. During this phase of PCa, circulating tumor cells (CTCs) are shed into the bloodstream and their presence and number are important in patient prognosis. The CellSearch® system (CSS) is the only U.S. Food and Drug Administration (FDA) and Health Canada approved instrument for detection of CTCs, making it the current clinical gold standard in CTC technology. Although the CSS provides a minimally invasive means of patient monitoring in the metastatic setting, little is known about the role of CTCs in …

Evidence For Differential Viral Oncolytic Efficacy In An In Vitro Model Of Epithelial Ovarian Cancer Metastasis, Jessica G. Tong, Yudith Ramos Valdes, John W. Barrett, John C. Bell, David Stojdl, Grant Mcfadden, J. Andrea Mccart, Gabriel E. Dimattia, Trevor G. Shepherd

Obstetrics & Gynaecology Publications

Epithelial ovarian cancer is unique among most carcinomas in that metastasis occurs by direct dissemination of malignant cells traversing throughout the intraperitoneal fluid. Accordingly, we test new therapeutic strategies using an in vitro three-dimensional spheroid suspension culture model that mimics key steps of this metastatic process. In the present study, we sought to uncover the differential oncolytic efficacy among three different viruses—Myxoma virus, double-deleted vaccinia virus, and Maraba virus—using three ovarian cancer cell lines in our metastasis model system. Herein, we demonstrate that Maraba virus effectively infects, replicates, and kills epithelial ovarian cancer (EOC) cells in proliferating adherent cells and …

Lgr5 Activates Tgfβ Signaling And Suppresses Metastasis In Colon Cancer, Xiaolin Zhou

Theses & Dissertations

Metastasis is the major cause of death in colorectal cancer patients, mainly due to the ineffectiveness of current therapies once metastases begin to form. Further insight into the biology of colorectal cancer metastasis is, therefore, essential in order to gain a greater understanding of this process and ultimately to develop better cancer therapies to prevent or target metastasis. LGR5 is leucine-rich repeat containing G protein-coupled receptor (GPCR) and was discovered as a marker for proliferating adult stem cells in the small intestine. LGR5 and its homologs LGR4 and LGR6 are receptors of R-spondins (RSPOs), which are secreted agonists of canonical …

Fibulin-3 Promotes Triple Negative Breast Cancer Cell Invasion, Michelle M. Noonan

Electronic Thesis and Dissertation Repository

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer, and metastasis is a leading cause of mortality in these patients. Fibulin-3, a secreted extracellular matrix protein, has a pro-invasive role in other cancers. However, a role for fibulin-3 in TNBC invasion is unknown. We have previously shown that KISS1R signaling promotes TNBC cell invasion through EGFR and MMP-9 activity, via β-arrestin2. Thus, we hypothesized that KISS1R signaling promotes TNBC cell invasion via fibulin-3. Our clinical data suggests that plasma fibulin-3 levels are elevated in metastatic TNBC patients. Additionally, we found that invasive breast cancer cells have increased …

Registered Report: Biomechanical Remodeling Of The Microenvironment By Stromal Caveolin-1 Favors Tumor Invasion And Metastasis, Steven Fiering, Lay-Hong Ang, Judith Lacoste, Tim D. Smith, Erin Griner

Dartmouth Scholarship

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replicating selected results from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012 were selected on the basis of citations and Altimetric scores (Errington et al., 2014). This Registered report describes the proposed replication plan of key experiments from ‘Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis’ by Goetz and colleagues, published in Cell in 2011 (Goetz et al., 2011). The key experiments …

An Unusual Initial Presentation Of Hepatocellular Carcinoma As A Sellar Mass, Nihar Shah Md, Yana Cavanagh, Hamid Shaaban, Beth Stein, Sohail N. Shaikh, Dharmesh H. Kaswala, Walid Baddoura

Gastroenterology

Sellar masses are frequently adenomatous pituitary tumors. Metastatic disease is unusual, often mimicking the presentations of adenomas. Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy but unusual to have a pituitary metastasis (PM). A 65-year-old man presented with headache, diplopia, ptosis, decreased vision in the right eye and unintentional weight loss of 32lbs. Preliminary out-patient work-up revealed a mass in the pituitary region. Cranial imaging showed 3.1 cm × 3.2 cm × 4.4 cm lesion. Abdominal imaging (computed tomography and magnetic resonance imaging) demonstrated a lobulated, nodular and heterogeneous right lobe of the liver. Trans-sphenoidal resection of the …

The Lung Microenvironment Influences The Metastatic Behaviour Of Breast Cancer Cells In An Innovative 3d Ex Vivo Pulmonary Metastasis Model, Matt M. Piaseczny

Electronic Thesis and Dissertation Repository

Lung metastasis remains a leading cause of death in breast cancer patients. This study established an innovative 3D ex vivo pulmonary metastasis assay (PuMA) to test the hypothesis that the lung microenvironment promotes metastatic behaviour of whole population and stem-like ALDH^hiCD44⁺ breast cancer cells. Following in vivo delivery of breast cancer cells to mice, lungs were excised, maintained in culture and imaged to observe breast cancer growth over time. We observed metastatic progression of breast cancer cells in the PuMA, most notably of ALDH^hiCD44⁺ cells which progressed rapidly from single cells to multicellular colonies …

The Role Of Bone-Derived Osteopontin In The Migration And Stem-Like Behavior Of Breast Cancer Cells, Graciella Pio

Electronic Thesis and Dissertation Repository

The majority of breast cancer deaths occur due to metastasis, with the most common site of breast cancer metastasis being bone. Previous work in our laboratory has established that stem-like breast cancer cells with high aldehyde dehydrogenase (ALDH) activity and expression of a CD44⁺CD24^- phenotype have enhanced metastatic capacity. This study tested the hypothesis that bone-derived osteopontin (OPN) promotes the migration and stem-like behavior of breast cancer cells. We demonstrate that bone- derived OPN promotes migration, tumorsphere-forming ability and colony-forming ability of whole population and ALDH^hiCD44⁺CD24^- breast cancer cells in bone marrow- …

In Vivo Characterization Of G Protein-Coupled Estrogen Receptor In Mammary Tumorigenesis, Nicole Marjon

Biomedical Sciences ETDs

The steroid hormone, estrogen (17β-estradiol or E2), is involved in numerous and varied physiological processes. Until recently, all E2-dependent effects were thought to be propagated exclusively through the classical estrogen receptors (ERs), ERα and ERβ. However, in double ERα/β knockout mice, select E2-dependent effects remain, suggesting the existence of additional E2 receptors, such as the G protein-coupled estrogen receptor (GPER) 1. E2 plays a central role in the progression of breast cancer, and inhibiting E2 signaling in women with breast cancer increases long-term survival. The role of GPER in breast cancer is largely unknown. E2 stimulation of GPER activates the …

A Novel Cytokine Profile Associated With Cancer Metastasis To Mediastinal And Hilar Lymph Nodes Identified Using Fine Needle Aspiration Biopsy, Ali Imran Saeed

Biomedical Sciences ETDs

Introduction: Cancer metastasis to mediastinal and hilar lymph nodes is indicative of a poor prognosis. It is thus important to understand the pathogenesis of cancer metastasis on a cellular and molecular level with a goal to develop novel therapies directed towards prevention and treatment. In this study we compared cytokine expression in benign versus malignant mediastinal and hilar lymph nodes using EBUS-FNA biopsy specimen. Methods: In this prospective, single center study, we collected EBUS-FNA biopsies from patients recruited using a convenience sampling approach. Cytokines were assayed using Bio-Plex Pro human cancer biomarker panels 1 and 2 in a Bio-Rad 200 …

Nfat1 Contributes To Melanoma Tumor Growth And Metastasis By Regulating Il-8 And Mmp-3, Einav Shoshan

Dissertations & Theses (Open Access)

Studies from our laboratory have recently demonstrated that Gal-3 regulates autotaxin through NFAT1 and support melanoma progression. These findings prompted us to further study the role of NFAT1 in melanoma progression and metastasis. NFAT1 is a transcription factor that was first identified in immune cells, acting as a positive regulator of interleukin-2 by binding to its promoter during T cell activation. NFAT1 has an important role in the innate and adaptive immune response. In this dissertation I studied the mechanisms by which NFAT1 contributes to the acquisition of the melanoma metastatic phenotype.

To identify the role of NFAT1 in melanoma …

Rampant Centrosome Amplification Underlies More Aggressive Disease Course Of Triple Negative Breast Cancers, Vaishali Pannu, Karuna Mittal, Guilherme Cantuaria, Michelle D. Reid, Xiaoxian Li, Shashikiran Donthamsetty, Michelle Mcbride, Sergey Klimov, Remus Osan, Meenakshi V. Gupta, Padmashree C.G. Rida, Ritu Aneja

Biology Faculty Publications

Centrosome amplification (CA), a cell-biological trait, characterizes pre-neoplastic and pre-invasive lesions and is associated with tumor aggressiveness. Recent studies suggest that CA leads to malignant transformation and promotes invasion in mammary epithelial cells. Triple negative breast cancer (TNBC), a histologically-aggressive subtype shows high recurrence, metastases, and mortality rates. Since TNBC and non- TNBC follow variable kinetics of metastatic progression, they constitute a novel test bed to explore if severity and nature of CA can distinguish them apart. We quantitatively assessed structural and numerical centrosomal aberrations for each patient sample in a large-cohort of grade-matched TNBC (n = 30) and non-TNBC …

Oncostatin M Binds To Extracellular Matrix In A Bioactive Conformation: Implications For Inflammation And Metastasis, Randall E. Ryan, Bryan Martin, Liliana Mellor, Reed B. Jacob, Ken Tawara, Owen M. Mcdougal, Julia Thom Oxford, Cheryl L. Jorcyk

Biology Faculty Publications and Presentations

Oncostatin M (OSM) is an interleukin-6-like inflammatory cytokine reported to play a role in a number of pathological processes including cancer. Full-length OSM is expressed as a 26 kDa protein that can be proteolytically processed into 24 kDa and 22 kDa forms via removal of C-terminal peptides. In this study, we examined both the ability of OSM to bind to the extracellular matrix (ECM) and the activity of immobilized OSM on human breast carcinoma cells. OSM was observed to bind to ECM proteins collagen types I and XI, laminin, and fibronectin in a pH-dependent fashion, suggesting a role for electrostatic …

Activation Of The Nf-Κb Pathway As A Mechanism Of Alcohol Enhanced Progression And Metastasis Of Human Hepatocellular Carcinoma, Fei Wang, Jin-Lian Yang, Ke-Ke Yu, Mei Xu, You-Zhi Xu, Li Chen, Yan-Min Lu, Hao-Shu Fang, Xin-Yi Wang, Zhong-Qian Hu, Fei-Fei Li, Lixin Kan, Jia Luo, Si-Ying Wang

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related death in human. Alcohol is a known risk factor for HCC. However it is still unclear whether and how alcohol enhances the progression and metastasis of existing HCC.

METHODS AND RESULTS: We first retrospectively investigated 52 HCC patients (24 alcohol-drinkers and 28 non-drinkers), and found a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC. Specifically, in …

5-Hydroxytryptamine Receptor (5-Ht1dR) Promotes Colorectal Cancer Metastasis By Regulating Axin1/Β-Catenin/Mmp-7 Signaling Pathway, Hua Sui, Hanchen Xu, Qing Ji, Xuan Liu, Lihong Zhou, Haiyan Song, Xiqiu Zhou, Yangxian Xu, Zhesheng Chen, Jianfeng Cai, Guang Ji, Qi Li

Chemistry Faculty Publications

Overexpression of 5-hydroxytryptamine (5-HT) in human cancer contributes to tumor metastasis, but the role of 5-HT receptor family in cancer has not been thoroughly explored. Here, we report overexpression of 5-HT_1D receptor (5-HT_1DR) was associated with Wnt signaling pathway and advanced tumor stage. The underlying mechanism of 5-HT_1DR-promoted tumor invasion was through its activation on the Axin1/β-catenin/MMP-7 pathway. In an orthotopic colorectal cancer mouse model, we demonstrated that a 5-HT_1DR antagonist (GR127935) effectively inhibited tumor metastasis through targeting Axin1. Furthermore, in intestinal epithelium cells, we observed that 5-HT_1DR played an important …

Human Cytomegalovirus Interleukin-10 Promotes Proliferation And Migration Of Mcf-7 Breast Cancer Cells, Robin K. Bishop, Cendy A. Valle Oseguera, Juliet Spencer

Biology Faculty Publications

Breast cancer is the most common malignancy affecting women worldwide. While a small fraction of breast cancers have a hereditary component, environmental and behavioral factors also impact the development of cancer. Human cytomegalovirus (HCMV) is a member of the Herpesviridae family that is widespread in the general population and has been linked to several forms of cancer. While HCMV DNA has been found in some breast cancer tissue specimens, we wanted to investigate whether a secreted viral cytokine might have an effect on cancerous or even pre-cancerous cells. HCMV encodes an ortholog of the human cellular cytokine interleukin-10 (IL-10). The …

Malignant Ectopic Thyroid Tissue With Distant Metastasis: A Case Report, Shehla Tabassum, Najmul Islam, Saulat H. Fatimi, Mubasher Ikram, Arsalan Ahmed, Maseehuz Zaman

Department of Medicine

Introduction: Ectopic thyroid tissue is the most common form of thyroid dysgenesis. But primary malignant transformation in ectopic thyroid tissue is quite a rare entity, with follicular malignancy being the dominant form at ectopic sites. Very infrequently, malignant ectopic thyroid tissue can present with metastasis to lymph nodes. But we report a case of malignant ectopic thyroid tissue over manubrium sterni with distant metastasis.
Case presentation: A 42-year-old Pakistani female presented with gradually increasing swelling on anterior aspect of manubrium sterni for last 6 months. She had no goitre and was clinically and biochemically euthyroid. Rest of systemic exam …

Creation Of A 3d Construct To Aid Cell Migration And Promote Cell Capture, Joseph Michael Sanders

Legacy Theses & Dissertations (2009 - 2024)

Most cancer-related deaths are attributed to metastasis. The tumor microenvironment is a complex environment which is not fully understood. The Nano Intravital Device (NANIVID) is a versatile, biocompatible device that allows for the manipulation of the tumor microenvironment in vitro and in vivo, providing a platform to study various aspects of tumor progression. The purpose of this study is to modify the NANIVID to resemble the tumor microenvironment in order to allow for a seamless transition from the in vivo environment into the engineered environment within the NANIVID. This engineered microenvironment will promote cell migration and cell capture. It has …

Determining The Effects Of Cd151 And Β1 On Tumor Cell Adhesion And Migration, Rachel R. Essex

Theses and Dissertations--Chemical and Materials Engineering

Previous studies have shown that the upregulation of CD151 and β₁ is associated with poor prognosis in many cancers such as breast cancer. Studies have provided evidence that these proteins are associated with the adhesion and migration of tumor cells. In this study, a microfluidic flow chamber was utilized to determine how CD151 and β₁ affected the firm and initial adhesion of metastatic breast cancer cells to a planar endothelial monolayer under shear stress. This system mimicked the adhesion of metastatic breast cancer cells to the endothelial cells of the circulatory system. CD151 and β₁ increased the …

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 …

Linking Adiponectin And Autophagy In The Regulation Of Breast Cancer Metastatic Potential, Emily Libby

All ETDs from UAB

Curative approaches for metastatic breast cancer remain elusive. Adiponectin is the most abundant of the adipocyte-secreted adipokines, and there is recent interest in development of adiponectin-based therapies for this disease. Yet, while multiple epidemiological studies have indicated that low levels of circulating plasma adiponectin portend poorer prognosis, recent work has reported that elevated adiponectin expression in breast tissue correlates with advanced disease. Further, isoform-specific roles of this molecule are not well understood. Thus, the overarching purpose of this work was to elucidate how adiponectin isoforms contribute to the microenvironmental regulation of the early steps of breast cancer metastasis. We show …