Cancer Biology Commons^™

Pvt1 Exon 9: A Potential Biomarker Of Aggressive Prostate Cancer?, Adeodat Ilboudo, Jyoti Chouhan, Brian K. Mcneil, Joseph R. Osborne, Olorunseun O. Ogunwobi

Publications and Research

Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest source of cancer-related mortality in males of African ancestry (MoAA). Interestingly, this has been shown to be associated with single nucleotide polymorphisms around regions 2 and 3 of the 8q24 human chromosomal region. The non-protein coding gene locus Plasmacytoma Variant Translocation 1 (PVT1) is located at 8q24 and is overexpressed in PCa and, therefore, is also a candidate biomarker to explain the well-known disparity in this group. PVT1 has at least 12 exons that make separate transcripts which may have different functions, all of which are …

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 …

The Role Of Cxcr2 In Pancreatic Cancer Development And Progression, Abhilasha Purohit

Theses & Dissertations

This dissertation examines the role of CXCR2, a seven transmembrane G- protein coupled receptor, in mediating autocrine as well as paracrine mechanisms during pancreatic cancer progression. Data presented in the initial section demonstrates the aberrant expression of the CXCR2 biological axis in human pancreatic cancer tissue specimens. A study performed within the first section of this dissertation investigates the contribution of CXCR2 signaling in pancreatic cancer initiation. These studies have identified a novel role of CXCR2 in mediating KRAS^(G12D) -induced autocrine growth transformation of pancreatic cancer cells. The upregulation of the CXCR2 biological axis was found to be directly …

Erbeta Regulation Of Nf-Kb Activation In Prostate Cancer Is Mediated By Hif-1, Paul Mak, Jiarong Li, Sanjoy Samanta, Arthur M. Mercurio

Arthur M. Mercurio

We examined the regulation of NF-kappaB in prostate cancer by estrogen receptor beta (ERbeta) based on the inverse correlation between p65 and ERbeta expression that exists in prostate carcinomas and reports that ERbeta can inhibit NF-kappaB activation, although the mechanism is not known. We demonstrate that ERbeta functions as a gate-keeper for NF-kappaB p65 signaling by repressing its expression and nuclear translocation. ERbeta regulation of NF-kappaB signaling is mediated by HIF-1. Loss of ERbeta or hypoxia stabilizes HIF-1alpha, which we found to be a direct driver of IKKbeta transcription through a hypoxia response element present in the promoter of the …

The Tumor Suppressor Notch Inhibits Head And Neck Squamous Cell Carcinoma (Hnscc) Tumor Growth And Progression By Modulating Proto-Oncogenes Axl And Ctnnal1 (Α-Catulin), Shhyam Moorthy, Shhyam Moorthy

Dissertations & Theses (Open Access)

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common malignancy worldwide, with roughly 300,000 cancer related deaths occurring globally each year. The survival of patients with HNSCC has not changed significantly over the past decade, leading investigators to search for promising molecular targets. To identify new treatment targets and biomarkers that could better guide therapy, we previously characterized the genomic alterations from primary HNSCC patient samples. We were among the first to discover that NOTCH1 is one of the most frequently mutated genes in this cancer type. The spectrum of inactivating NOTCH1 mutations in HNSCC suggested …

Identifying Protein Kinase Tbk1 As A Novel Inhibitor Of Intestinal Tumorigenesis, Amber L. Mathews

Dissertations & Theses (Open Access)

Colorectal cancer (CRC) is the third most common cancer diagnosed in women and men， causing almost 600,000 annual deaths worldwide. There is a clear need to understand how CRC forms and progresses in order to improve the strategies of CRC prevention and therapy. A major factor that drives the development of CRC is genetic mutations that lead to activation of oncogenes and inactivation of tumor suppressor genes in intestinal epithelial cells (IECs). In addition, the initiation and progression of CRC involve environmental and immunological factors. In particular, chronic inflammatory conditions are known as an important risk factor for CRC. Intestinal …

Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd

Dissertations & Theses (Open Access)

Normal Glycolytic Enzyme Activity is Critical for Hypoxia Inducible Factor-1α Activity and Provides Novel Targets for Inhibiting Tumor Growth

By Geoffrey Grandjean

Advisory Professor: Garth Powis, D. Phil

Unique to proliferating cancer cells is the observation that their increased need for energy is provided by a high rate of glycolysis followed by lactic acid fermentation in a process known as the Warburg Effect, a process many times less efficient than oxidative phosphorylation employed by normal cells to satisfy a similar energy demand ^[1]. This high rate of glycolysis occurs regardless of the concentration of oxygen in the cell and …

Regulation Of The Retinoblastoma Tumor Suppressor By The Novel Ras Effector Nore1a., Thibaut François Barnoud

Electronic Theses and Dissertations

Ras is the most frequently mutated oncogene in human cancers. It acts as a critical branch point in signal transduction, regulating numerous downstream effectors involved in cell growth and differentiation. While Ras can activate many growth promoting pathways, it can paradoxically regulate growth inhibitory pathways leading to apoptosis and cell cycle arrest. One of the ways Ras can inhibit the growth of cells is via a family of effectors called the RASSF proteins. RASSF5 (NORE1A) is a tumor suppressor that is frequently inactivated in human tumors by epigenetic mechanisms. NORE1A binds directly to Ras and promotes Ras-induced senescence. We have …

The Ras Effector Nore1a Forms A Tumor Suppressor Complex With Brca1., Nicholas C Nelson

Electronic Theses and Dissertations

Ras proteins function as molecular signaling switches that can stimulate multiple mitogenic pathways in response to extracellular signaling. Oncogenic activation of Ras by structural mutation is a highly transforming event in ~1/3 of human cancers. However, aberrant Ras activation can also promote oncogene-induced senescence. This Ras-induced irreversible growth arrest is a physiological process that acts as a barrier to malignancy. The mechanisms by which Ras drives senescence and how this process is bypassed during Ras-driven transformation remains poorly understood.

Although mutations in the RAS gene are extremely rare in human breast cancer, the Ras signaling pathway is constitutively activated in …

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 ( …

The Chemopreventive Effect Of Polymethoxyflavones: Targeting The Colorectal Cancer Stem Cells, Fei Xu

Doctoral Dissertations

Among all the cancers, the death rate of colorectal cancer is one of the highest. Evidence from both murine xenograft model and human trials have shown cancer stem cells (CSCs) are responsible for the initiation, metastasis and recurrence of multiple cancers therefore targeting colorectal CSCs would be a promising chemo-preventive/ therapeutic strategy. Polymethoxyflavones including nobiletin (NBT) and 5-demethylatednobiletin (5DN) are exclusively found in citrus peels and have been shown to have anti-cancer effects. Our previous studies in the biotransformation and tissue distribution of NBT and 5DN have shown that in order to fuller evaluate the biological impact of those two …

The Investigation Of Rhodiola Crenulata Root Extract Effects On Obesity Associated Inflammation And The Antineoplastic Mechanism In Breast Cancer Cells, Lotfi M. Bassa

Doctoral Dissertations

Obesity and breast cancer are two disease models that directly affect the United States population, as more than 35% of the adult population is obese [8], and more than 200,000 new cases of breast cancer are diagnosed in the United States per year [34]. Several diseases are associated with obesity including, cardiovascular disease, insulin resistance, increased inflammation and increased cancer risk [9,10]. Therefore it essential to understand the risks associated with obesity as well as to investigate possible preventive and/or therapeutic treatment strategies. Rhodiola crenulata is a Tibetan plant that has been used in Eastern traditional medicine to relieve depression, …

Mcnamara 201412 Nih Scap Innocentive Challenge Solution - T-Bow Rainbow T-Cells And Tumor Cells Spatial Multiplexing Gene Expression Reporter System – Plus Supplement Plus Posters - 20151027 - Please Download "75" Instead, George Mcnamara

George McNamara

McNamara 201412 NIH SCAP InnoCentive Challenge Solution - T-Bow Rainbow T-cells and Tumor Cells Spatial Multiplexing Gene Expression Reporter System – plus supplement plus posters - 20151027.

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Please download the current 20151027 (October 27, 2015) Tattletales and T-Bow update from

http://works.bepress.com/gmcnamara/75/

The bepress web site is not letting me replace the old pdf here at "65" with the additional 10 pages update.

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The download is my/Cooper lab solution (submission) to the 2014 NIH Single Cell Analysis Program (SCAP) InnoCentive Challenge, "Follow That Cell". I submitted the Solution on 20141215Mon (with 20 minutes to spare). The Challenge web page …

Tattletales And T-Bow Update 20151027tue, George Mcnamara

George McNamara

20151027Tue this "75"

http://works.bepress.com/gmcnamara/75

is my update of "65" posting

See text at

http://works.bepress.com/gmcnamara/65/

for text summary. The PDf here in "75" supersedes "65".

The PDF here has 10 pages added to the end from the "65" version (pages 40-49 of PDF when including the bepress cover page)..

here is the text in my cover page (bepress may add its own cover):

20151027Tue: added 10 page e-poster at bottom explaining Binary Tattletales and T-Bow. That is, binary with respect to protein components. For one color (number of repeats, epitope tags, FPs are examples, here rounded to convenient numbers):

1. 100 …

Real-Time Detection Of Breast Cancer Cells Using Peptidefunctionalized Microcantilever Arrays, Hashem Etayash, Keren Jiang, Sarfuddin Azmi, Thomas Thundat, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Ligand-directed targeting and capturing of cancer cells is a new approach for detecting circulating tumor cells (CTCs). Ligands such as antibodies have been successfully used for capturing cancer cells and an antibody based system (CellSearch®) is currently used clinically to enumerate CTCs. Here we report the use of a peptide moiety in conjunction with a microcantilever array system to selectively detect CTCs resulting from cancer, specifically breast cancer. A sensing microcantilever, functionalized with a breast cancer specific peptide 18-4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB-231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells. …

Characterizing The C-Terminal Region Of Human Adenovirus E1a: An Undiscovered Country, Michael J. Cohen

Electronic Thesis and Dissertation Repository

Human Adenovirus (HAdV) E1A is the first protein expressed during viral infection. The primary function of E1A is to reprogram the cell for viral replication, but it is additionally capable of transforming primary rodent cells in co-operation with other oncogenes such as HAdV E1B. Despite extensive study, little is known about the function and cellular targets of the C-terminal region of E1A. Importantly, this region is required for the transforming ability of E1A with E1B, but can also suppress transformation with Ras. Previous studies showed that interaction with the C-terminal Binding Protein (CtBP) plays a role in both functions described …

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 …

Clinical Significance Of The Integrin Α6Β4 In Human Malignancies, Rachel L Stewart, Kathleen L O'Connor

Pathology and Laboratory Medicine Faculty Publications

Integrin α6β4 is a cellular adhesion molecule that binds to laminins in the extracellular matrix and nucleates the formation of hemidesmosomes. During carcinoma progression, integrin α6β4 is released from hemidesmosomes, where it can then signal to facilitate multiple aspects of tumor progression including sustaining proliferative signaling, tumor invasion and metastasis, evasion of apoptosis, and stimulation of angiogenesis. The integrin achieves these ends by cooperating with growth factor receptors including EGFR, ErbB-2, and c-Met to amplify downstream pathways such as PI3K, AKT, MAPK, and the Rho family small GTPases. Furthermore, it dramatically alters the transcriptome …

Engineering Novel Detection And Treatment Strategies For Bacterial Therapy Of Cancer, Jan T. Panteli

Doctoral Dissertations

Finding and treating cancer is difficult due to limited sensitivity and specificity of current detection and treatment strategies. Many chemotherapeutic drugs are small molecules that are limited by diffusion, making it difficult to reach cancer sites requiring high doses that lead to systemic toxicity and off-target effects. Tomographic detection techniques, like PET, MRI and CT, are good at identifying macroscopic lesions in the body but are limited in their ability to detect microscopic lesions. Biomarker detection strategies are extremely sensitive and able to identify ng/ml concentrations of protein, but are poor at discriminating between healthy and disease state levels due …

Mimicking The Arterial Microenvironment With Peg-Pc To Investigate The Roles Of Physicochemical Stimuli In Smc Phenotype And Behavior, William G. Herrick

Doctoral Dissertations

The goal of this dissertation was to parse the roles of physical, mechanical and chemical cues in the phenotype plasticity of smooth muscle cells (SMCs) in atherosclerosis. We first developed and characterized a novel synthetic hydrogel with desirable traits for studying mechanotransduction in vitro. This hydrogel, PEG-PC, is a co-polymer of poly(ethylene glycol) and phosphorylcholine with an incredible range of Young’s moduli (~1 kPa - 9 MPa) that enables reproduction of nearly any tissue stiffness, exceptional optical and anti-fouling properties, and support for covalent attachment of extracellular matrix (ECM) proteins. To our knowledge, this combination of mechanical range, low …

The Role Of Connexins And Pannexins In Mammary Gland Development And Tumorigenesis, Michael K. G. Stewart

Electronic Thesis and Dissertation Repository

The identification of key regulators of breast cancer onset and progression is critical for the development of targeted therapies. Connexins and pannexins are characterized by their ability to form large-pore channels and are frequently dysregulated in cancer. However, their role in breast cancer progression remains poorly understood due to a lack of in vivo models capable of assessing the proposed and opposing roles of connexins and pannexins as both tumor suppressors and/or facilitators in multiple stages of the disease. Using 2 previously uncharacterized genetically-modified mice, connexin43 (Cx43) and connexin26 (Cx26) were evaluated for their role in normal mammary gland development …

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 …

Role Of Hippo-Yap Signaling In Mitosis And Prostate Cancer, Lin Zhang

Theses & Dissertations

The Hippo pathway controls organ size and tumorigenesis by inhibiting cell proliferation and promoting apoptosis. KIBRA [kidney and brain expressed protein] is an upstream regulator of the Hippo-YAP signaling. The role KIBRA plays in mitosis has not been established. We show that KIBRA activates the Aurora kinases during mitosis and KIBRA promotes the phosphorylation of large tumor suppressor 2 by activating Aurora-A. We further show that knockdown of KIBRA causes mitotic abnormalities, including defects of spindle and centrosome formation and chromosome misalignment. The transcriptional co-activator with PDZ-binding motif is a downstream effector of the Hippo tumor suppressor pathway. In the …

Three-Dimensional Confocal Microscopy Indentation Method For Hydrogel Elasticity Measurement, Donghee Lee, Md Mahmudur Rahman, You Zhou, Sangjin Ryu

Md Mahmudur Rahman

No abstract provided.

Crosstalk Between Brca-Fanconi Anemia And Mismatch Repair Pathways Prevents Msh2-Dependent Aberrant Dna Damage Responses, Min Peng, Jenny X. Xie, Anna J. Ucher, Janet Stavnezer, Sharon B. Cantor

Janet M. Stavnezer

Several proteins in the BRCA-Fanconi anemia (FA) pathway, such as FANCJ, BRCA1, and FANCD2, interact with mismatch repair (MMR) pathway factors, but the significance of this link remains unknown. Unlike the BRCA-FA pathway, the MMR pathway is not essential for cells to survive toxic DNA interstrand crosslinks (ICLs), although MMR proteins bind ICLs and other DNA structures that form at stalled replication forks. We hypothesized that MMR proteins corrupt ICL repair in cells that lack crosstalk between BRCA-FA and MMR pathways. Here, we show that ICL sensitivity of cells lacking the interaction between FANCJ and the MMR protein MLH1 is …

Detection Of Ubiquitination On Syk And Documenting Syk Stability, Izabela Mazur, Wen Horng Wang, Robert J. Geahlen

The Summer Undergraduate Research Fellowship (SURF) Symposium

Post-translational modifications regulate the activities of proteins important to numerous diseases. Spleen Tyrosine Kinase (Syk) is particularly interesting to researchers because it modifies many targets and plays multiple roles in regulating cells in our bodies and its abnormal modifications may contribute to cancer, Alzheimer’s disease and allergies. In an attempt to study these modifications of Syk, we first looked at detecting ubiquitination on Syk protein. Ubiquitin, a small 8 kDa molecule, attaches to lysine residues on protein. The attachment of ubiquitin to Syk may cause Syk to either propagate signals onwards to activate other proteins or signal it to undergo …

Elucidating The Role Of Hausp Ubiquitin Like Domains In The Catalytic Function Of Usp7, Anuj Patel, Nicole Davis, Andrew Mesecar

The Summer Undergraduate Research Fellowship (SURF) Symposium

Ubiquitin specific proteases (USPs) are a class of enzymes involved in myriad cellular processes. One USP of great interest due to its oncogenic properties is USP7. In normal conditions USP7 is closely regulated due to its responsibility for destabilizing the tumor suppressor, p53, through the deubiquitination of MDM2. In multiple myeloma cases, it appears the regulation of USP7 subsides, as it is largely overexpressed, leading to the inappropriate degradation of p53. Inhibition of USP7 could, therefore, prove a viable target for cancer therapy. A greater understanding of USP7’s function and structure can lead to more insight into how this enzyme …

Investigations Into The Modification Of Dna By Doxorubicin Analogs, Hannah Kulm, Stephanie Torres, Chris Mallory, Kenneth Cornell (Mentor), Don Warner (Mentor)

Idaho Conference on Undergraduate Research

Doxorubicin (DOX) is an anthracycline chemotherapeutic that has seen widespread use to treat numerous cancer types. Its mechanism of action is still unclear, but is thought to include the intercalation of DNA, halting transcription and inducing apoptosis. Although DOX has shown strong antitumor activity, its usage is limited due to a dose-dependent onset of cumulative and irreversible life-threatening cardiac damage. Consequently, the harmful side effects necessitate the need for the production of new, less harmful anthracycline chemotherapeutics with greater effectiveness for the treatment of cancer. Three analogs of DOX (P-DOX, GPX-150 and GPX-160) have been synthesized and determined to have …

Effects Of A Particular Heptapeptide On The Ifn-Α-Sensitive Cml Cells, Fulan Yang, Fangzhi Chen, Xinxing Wan, Xi Zhou, Meijuan Zhou, Hanchun Chen, Junjiang Fu, Dianzheng Zhang

PCOM Scholarly Papers

Abstract: Using the phage display biopanning technique, we have previously identified a heptapeptide KLWVIPQ which specifically bind to the surface of the IFN-α sensitive but not the IFN-α-resistant CML cells. The effects of this heptapeptide to the IFN-α-sensitive CML cells were investigated in the present study. IFN-α-sensitive KT-1/A3 and IFN-α-resistant KT-1/A3R CML cells were transfected by pEGFP KLWVIPQ expression vector and/or induced by IFN-α. WST-1 cell proliferation assay, flow cytometry and western blotting were performed to determine the effects of this heptapeptide and/or IFN-α on CML cells. The viability of the KT-1/A3 cells w as inhibited and apoptosis was induced …

Direct Regulation Of Apoptosis By Linear Ubiqutin Chain Assembly Complex (Lubac) And Feedback Regulation Of Lubac Function By Caspases, Donghyun Joo

Dissertations & Theses (Open Access)

Tumor Necrosis Factor-alpha (TNF-α) is a cytokine that plays a role in various cellular processes such as proliferation, differentiation (mainly through NF-κB signaling) and death (via apoptosis signaling). Recently, linear ubiquitination by LUBAC (linear ubiquitin chain assembly complex) was reported to have a regulatory function in TNF-α mediated NF-κB activation. Although LUBAC is suggested to control not only NF-kB signaling but also the apoptosis pathway, the precise mechanism of apoptosis regulation remains unknown. Moreover, NF-κB and apoptosis pathways have opposed but fundamental functions for various cellular processes. Although these two pathways actively interplay to balance the death and survival, the …