Medical Cell Biology Commons^™

Prostate Field Cancerization And Exosomes: Association Between Cd9, Early Growth Response 1 And Fatty Acid Synthase, Farideh Amirrad, Philip A. Pytak, Neda Sadeghiani-Pelar, Julie P. T. Nguyen, Emily L. Cauble, Anna C. Jones

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Intracapsular and well‑defined adenocarcinomas of the prostate are often surrounded by tissue areas that harbor molecular aberrations, including those of genetic, epigenetic and biochemical nature. This is known as field cancerization, or a field effect and denotes a state of pre‑malignancy. Such alterations in histologically normal tumor‑adjacent prostatic tissues have been recognized as clinically important and are potentially exploitable as biomarkers of disease and/or targets for preventative/therapeutic intervention. The authors have previously identified and validated two protein markers of field cancerization: The expressional upregulation of the transcription factor early growth response 1 (EGR‑1) and the lipogenic enzyme fatty acid synthase …

First-Time Characterization Of Viable But Non-Culturable Proteus Mirabilis: Induction And Resuscitation, Reham Wasfi, G. R. Abdellatif, H. M. Elshishtawy, Hossam M. Ashour

USF St. Petersburg Campus Faculty Publications

Pathogenic bacteria can enter into a viable but non-culturable (VBNC) state under unfavourable conditions. Proteus mirabilis is responsible for dire clinical consequences including septicaemia, urinary tract infections and pneumonia, but is not a species previously known to enter VBNC state. We suggested that stress-induced P. mirabilis can enter a VBNC state in which it retains virulence. P. mirabilis isolates were incubated in extreme osmotic pressure, starvation, low temperature and low pH to induce a VBNC state. Resuscitation was induced by temperature upshift and inoculation in tryptone soy broth with Tween 20 and brain heart infusion broth. Cellular ultrastructure and gene …

Social Media Engagement At Academic Conferences: Report Of The Association Of Pathology Chairs 2018 And 2019 Annual Meeting Social Media Committee, Yonah C. Ziemba, Dana Razzano, Timothy C. Allen, Adam L. Booth, Scott R. Anderson, Anne Champeaux, Michael D. Feldman, Valerie Fitzhugh, Simone Gittens, Marilea Grider, Mary Gupta, Christina Hanos, Karen Kelly, Tarush Kothari, Jennifer Laudadio, Amy Y. Lin, Kamran M. Mirza, Kathleen T. Montone, Priscilla S. Markwood

Pathology and Cell Biology Faculty Publications

The use of social media at academic conferences is expanding, and platforms such as Twitter are used to share meeting content with the world. Pathology conferences are no exception, and recently, pathology organizations have promoted social media as a way to enhance meeting exposure. A social media committee was formed ad hoc to implement strategies to enhance social media involvement and coverage at the 2018 and 2019 annual meetings of the Association of Pathology Chairs. This organized approach resulted in an 11-fold increase in social media engagement compared to the year prior to committee formation (2017). In this article, the …

Utilizing Social Media To Spread Knowledge: The Association Of Pathology Chairs Experience At The 2018 Annual Meeting, Dana Razzano, Yonah C. Ziemba, Adam L. Booth, Priscilla Markwood, Christina T. Hanos, Nicole Riddle

Pathology and Cell Biology Faculty Publications

No abstract provided.

Examining The Role Of Metabolic Pathways As Therapeutic Modalities For Triple Negative Breast Cancer, Jeremy Andrew Johnson

Theses and Dissertations--Toxicology and Cancer Biology

Triple negative breast cancer (TNBC) comprises 15-20% of breast cancers, affects a younger patient population than other subtypes, and is very aggressive. TNBC is comprised of a diverse group of tumors that have proven refractory to targeted therapy and can be difficult to treat. Patients generally receive neoadjuvant chemotherapy (NAC), surgery, and radiotherapy. The standard of care for NAC includes a taxane, an anthracycline, and/or cyclophosphamide, and administration of NAC has resulted in pathological complete response (pCR) in 30-40% of patients. However, a majority of TNBC patients will not reach pCR and instead have residual disease (RD), which is associated …

Modulation Of Epileptogenesis: A Paradigm For The Integration Of Enzyme-Based Microelectrode Arrays And Optogenetics, Corwin R. Butler, Jeffery A. Boychuk, Francois Pomerleau, Ramona Alcala, Peter Huettl, Yi Ai, Johan Jakobsson, Sidney W. Whiteheart, Greg A. Gerhardt, Bret N. Smith, John T. Slevin

Physiology Faculty Publications

BACKGROUND: Genesis of acquired epilepsy includes transformations spanning genetic-to- network-level modifications, disrupting the regional excitatory/inhibitory balance. Methodology concurrently tracking changes at multiple levels is lacking. Here, viral vectors are used to differentially express two opsin proteins in neuronal populations within dentate gyrus (DG) of hippocampus. When activated, these opsins induced excitatory or inhibitory neural output that differentially affected neural networks and epileptogenesis. In vivo measures included behavioral observation coupled to real-time measures of regional glutamate flux using ceramic-based amperometric microelectrode arrays (MEAs).

RESULTS: Using MEA technology, phasic increases of extracellular glutamate were recorded immediately upon application of blue light/488 nm …

Perioperative Acute Kidney Injury, Sam D Gumbert, Felix Kork, Maisie L Jackson, Naveen Vanga, Semhar J Ghebremichael, Christy Y Wang, Holger K Eltzschig

Faculty, Staff and Students Publications

Perioperative organ injury is among the leading causes of morbidity and mortality of surgical patients. Among different types of perioperative organ injury, acute kidney injury occurs particularly frequently and has an exceptionally detrimental effect on surgical outcomes. Currently, acute kidney injury is most commonly diagnosed by assessing increases in serum creatinine concentration or decreased urine output. Recently, novel biomarkers have become a focus of translational research for improving timely detection and prognosis for acute kidney injury. However, specificity and timing of biomarker release continue to present challenges to their integration into existing diagnostic regimens. Despite many clinical trials using various …

Telomere Shortening And Cellular Senescence Induced By Oxalate And Nephrolithiasis Urine In Hk-2 Cells, Kamonchanok Chuenwisad

Chulalongkorn University Theses and Dissertations (Chula ETD)

Kidney stone disease is a common urologic problem worldwide, especially in the tropics such as Thailand. It is known as a multifactorial condition, and aging increases the risk of stone development. The major type of stones is calcium oxalate (CaOx), and its formation is driven by increased urinary oxalate excretion and calcium oxalate monohydrate (COM) crystallization. Both oxalate and COM are known to induce reactive oxygen species (ROS) production and cause oxidative stress. Furthermore, patients with CaOx stone have increased extent of oxidative stress. In this study, we investigated the induction of cellular senescence and telomere shortening through oxidative stress …

Multiple Mitochondrial Thioesterases Have Distinct Tissue And Substrate Specificity And Coa Regulation, Suggesting Unique Functional Roles., Carmen Bekeova, Lauren Anderson-Pullinger, Kevin Boye, Felix Boos, Yana Sharpadskaya, Johannes M Herrmann, Erin L. Seifert

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Acyl-CoA thioesterases (Acots) hydrolyze fatty acyl-CoA esters. Acots in the mitochondrial matrix are poised to mitigate β-oxidation overload and maintain CoA availability. Several Acots associate with mitochondria, but whether they all localize to the matrix, are redundant, or have different roles is unresolved. Here, we compared the suborganellar localization, activity, expression, and regulation among mitochondrial Acots (Acot2, -7, -9, and -13) in mitochondria from multiple mouse tissues and from a model of Acot2 depletion. Acot7, -9, and -13 localized to the matrix, joining Acot2 that was previously shown to localize there. Mitochondria from heart, skeletal muscle, brown adipose tissue, and …

Residues And Residue Pairs Of Evolutionary Importance Differentially Direct Signaling Bias Of D2 Dopamine Receptors, María E Terrón-Díaz, Sara J Wright, Melina A Agosto, Olivier Lichtarge, Theodore G Wensel

Faculty, Staff and Students Publications

The D2 dopamine receptor and the serotonin 5-hydroxytryptamine 2A receptor (5-HT2A) are closely-related G-protein–coupled receptors (GPCRs) from the class A bioamine subfamily. Despite structural similarity, they respond to distinct ligands through distinct downstream pathways, whose dysregulation is linked to depression, bipolar disorder, addiction, and psychosis. They are important drug targets, and it is important to understand how their bias toward G-protein versus β-arrestin signaling pathways is regulated. Previously, evolution-based computational approaches, difference Evolutionary Trace and Evolutionary Trace–Mutual information (ET-Mip), revealed residues and residue pairs that, when switched in the D2 receptor to the corresponding residues from 5-HT2A, altered ligand potency …

Examining Multiple Cellular Pathways At Once Using Multiplex Hextuple Luciferase Assaying, Alejandro Sarrion-Perdigones, Lyra Chang, Yezabel Gonzalez, Tatiana Gallego-Flores, Damian W Young, Koen J T Venken

Faculty, Staff and Students Publications

Sensitive simultaneous assessment of multiple signaling pathways within the same cells requires orthogonal reporters that can assay over large dynamic ranges. Luciferases are such genetically encoded candidates due to their sensitivity, versatility, and cost-effectiveness. We expand luciferase multiplexing in post-lysis endpoint luciferase assays from two to six. Light emissions are distinguished by a combination of distinct substrates and emission spectra deconvolution. All six luciferase reporter units are stitched together into one plasmid facilitating delivery of all reporter units through a process we termed solotransfection, minimizing experimental errors. We engineer a multiplex hextuple luciferase assay to probe pathway fluxes through five …

Interaction Of The Oncoprotein Transcription Factor Myc With Its Chromatin Cofactor Wdr5 Is Essential For Tumor Maintenance., Lance R. Thomas, Clare M. Adams, Jing Wang, April M. Weissmiller, Joy Creighton, Shelly L. Lorey, Qi Liu, Stephen W. Fesik, Christine M. Eischen, William P. Tansey

Department of Cancer Biology Faculty Papers

The oncoprotein transcription factor MYC is overexpressed in the majority of cancers. Key to its oncogenic activity is the ability of MYC to regulate gene expression patterns that drive and maintain the malignant state. MYC is also considered a validated anticancer target, but efforts to pharmacologically inhibit MYC have failed. The dependence of MYC on cofactors creates opportunities for therapeutic intervention, but for any cofactor this requires structural understanding of how the cofactor interacts with MYC, knowledge of the role it plays in MYC function, and demonstration that disrupting the cofactor interaction will cause existing cancers to regress. One cofactor …

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …

Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina

Dissertations and Theses (Open Access)

Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal …

Identification Of Monocyte-Like Precursors Of Granulocytes In Cancer As A Mechanism For Accumulation Of Pmn-Mdscs., Jérôme Mastio, Thomas Condamine, George Dominguez, Andrew V Kossenkov, Laxminarasimha Donthireddy, Filippo Veglia, Cindy Lin, Fang Wang, Shuyu Fu, Jie Zhou, Patrick Viatour, Sergio Lavilla-Alonso, Alexander T. Polo, Evgenii N. Tcyganov, Charles Mulligan, Brian Nam, Joseph Bennett, Gregory Masters, Michael Guarino, Amit Kumar, Yulia Nefedova, Robert H. Vonderheide, Lucia R. Languino, Scott I. Abrams, Dmitry I. Gabrilovich

Department of Cancer Biology Faculty Papers

We have identified a precursor that differentiates into granulocytes in vitro and in vivo yet belongs to the monocytic lineage. We have termed these cells monocyte-like precursors of granulocytes (MLPGs). Under steady state conditions, MLPGs were absent in the spleen and barely detectable in the bone marrow (BM). In contrast, these cells significantly expanded in tumor-bearing mice and differentiated to polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Selective depletion of monocytic cells had no effect on the number of granulocytes in naive mice but decreased the population of PMN-MDSCs in tumor-bearing mice by 50%. The expansion of MLPGs was found to be …

Activation Of Lxrβ Inhibits Tumor Respiration And Is Synthetically Lethal With Bcl-Xl Inhibition, Trang Thi Thu Nguyen, Chiaki Tsuge Ishida, Enyuan Shang, Chang Shu, Consuelo Torrini, Yiru Zhang, Elena Bianchetti, Maria J. Sanchez-Quintero, Giulio Kleiner, Catarina M. Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Peter Canoll, Markus D. Siegelin

Publications and Research

Liver-X-receptor (LXR) agonists are known to bear anti-tumor activity. However, their efficacy is limited and additional insights regarding the underlying mechanism are necessary. By performing transcriptome analysis coupled with global polar metabolite screening, we show that LXR agonists, LXR623 and GW3965, enhance synergistically the anti-proliferative effect of BH3 mimetics in solid tumor malignancies, which is predominantly mediated by cell death with features of apoptosis and is rescued by exogenous cholesterol. Extracellular flux analysis and carbon tracing experiments (U-¹³C-glucose and U-¹³C-glutamine) reveal that within 5 h, activation of LXRβ results in reprogramming of tumor cell metabolism, leading …

Generation Of An Oncolytic Adenovirus Targeting The Cxcr4 And Cxcr7 Chemokine Receptors In Breast Cancer, Samia Melissa O'Bryan

LSU Doctoral Dissertations

Breast cancer is the most diagnosed cancer in women under 60 and the second most diagnosed cancer in women over 60. While treatments for localized breast cancer are quite successful with high survival rates at 99%, advanced breast cancer remains hard to treat with a nearly 75% decrease in survival. Current treatments are inefficient at treating advanced stages of breast cancer, and thus, new therapies are sorely needed to address the complexity of advanced stage breast cancer. The ideal therapy would be capable of systemic administration, targets cancer cells and spares normal tissue. Oncolytic adenovirus is an ideal therapeutic vector …

N-Glycosylation-Defective Splice Variants Of Neuropilin-1 Promote Metastasis By Activating Endosomal Signals, Xiuping Huang, Qing Ye, Min Chen, Aimin Li, Wenting Mi, Yuxin Fang, Yekaterina Y. Zaytseva, Kathleen L. O'Connor, Craig W. Vander Kooi, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes. This increased endocytic trafficking of the two NRP1 variants, upon HGF stimulation, is due to loss of N-glycosylation at the Asn150 or Asn261 site, respectively. Moreover, these NRP1 variants enhance interactions with the Met and β1-integrin receptors, resulting in Met/β1-integrin co-internalization and co-accumulation on endosomes. This provides persistent …

The Bone Extracellular Matrix As An Ideal Milieu For Cancer Cell Metastases., Alexus D. Kolb, Karen M. Bussard

Department of Cancer Biology Faculty Papers

Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstances, two of the main cell types in bone, the osteoblasts and osteoclasts, help to …

M6a Mrna Demethylase Fto Regulates Melanoma Tumorigenicity And Response To Anti-Pd-1 Blockade, Seungwon Yang, Jiangbo Wei, Yan-Hong Cui, Gayoung Park, Palak Shah, Yu Deng, Andrew E. Aplin, Zhike Lu, Seungmin Hwang, Chuan He, Yu-Ying He

Department of Cancer Biology Faculty Papers

Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N⁶-methyladenosine (m⁶A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-κB pathway. Knockdown of FTO increases m⁶A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m⁶A reader YTHDF2. Knockdown of …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel

Honors Scholar Theses

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

The Role Of Ros In The Progression And Treatment Of Castration-Resistant Prostate Cancer, Dannah R. Miller

Theses & Dissertations

Prostate cancer is the second leading cause of cancer-related deaths in U.S. men, primarily due to the development of castration-resistant (CR) prostate cancer (PCa), of which there are no effective treatment options. Reactive oxygen species (ROS) plays a critical role in prostate carcinogenesis, including the progression of the CR PCa phenotype. ROS regulates both cell proliferation and apoptosis; a moderate increase in ROS can promote proliferation; however, a substantial rise in ROS levels will result in apoptosis. Oxidase p66Shc is elevated in clinical PCa cells and has been associated with a metastatic phenotype of CR PCa cells, promoting PCa cell …

Differential Iron Regulatory Genetics In 2d & 3d Culture Of Breast Cancer Cells, Tyler Hanna, Suzy Torti Ph. D, Frank Torti M.D., Mph, Nicole Farra Ph. D.

Honors Scholar Theses

The iron regulatory axis has consistently been shown to be perturbed in cancer cell lines relative to non-cancerous cell lines. As cancer cells rapidly divide and grow, they require iron to fuel many intracellular processes, including DNA replication and protein synthesis. Three-dimensional cell culture is an increasingly popular method of culture that purportedly more accurately mimics the in vivo microenvironment of cancers over traditional two-dimensional culture. This project was prompted by previous lab results to investigate differential iron regulatory gene expression in 2D and 3D spheroid culture models. We replicated the findings that the gene hepcidin is induced in 3D …

Tumor-Derived Extracellular Vesicles Require Β1 Integrins To Promote Anchorage-Independent Growth., Rachel M. Derita, Aejaz Sayeed, Vaughn Garcia, Shiv Ram Krishn, Christopher D. Shields, Srawasti Sarker, Andrea Friedman, Peter Mccue, Sudheer Kumar Molugu, Ulrich Rodeck, Adam P. Dicker, Lucia R. Languino

Department of Cancer Biology Faculty Papers

The β1 integrins, known to promote cancer progression, are abundant in extracellular vesicles (EVs). We investigated whether prostate cancer (PrCa) EVs affect anchorage-independent growth and whether β1 integrins are required for this effect. Specifically using a cell-line-based genetic rescue and an in vivo PrCa model, we show that gradient-purified small EVs (sEVs) from either cancer cells or blood from tumor-bearing TRAMP (transgenic adenocarcinoma of the mouse prostate) mice promote anchorage-independent growth of PrCa cells. In contrast, sEVs from cultured PrCa cells harboring a short hairpin RNA to β1, from wild-type mice or from TRAMP mice carrying a β1 conditional ablation …

Dual Therapy Treatment Of Pediatric Acute Lymphoblastic Leukemia With Blinotumomab And A Standard Chemotherapy Regimen, Tori I. Scheffler

Selected Honors Theses

Leukemia is the number one cancer affecting children in the nation, with acute lymphoblastic leukemia being the most prevalent classification.1 While new and innovative treatment protocols have greatly increased the success rate of primary cancer patients, those who face relapse receive a much more dismal prognosis. Recent studies have shown that patients who relapse quite frequently have developed drug-resistant clones of the original cancer cells, leading to a need for various secondary treatment options. The drug-resistance is due to clonal mutations that take place within the cancer cell, most often because of an outside pressure or stress within the environment …

Itch Nuclear Translocation And H1.2 Polyubiquitination Negatively Regulate The Dna Damage Response, Lufen Chang, Lei Shen, Hu Zhou, Jing Gao, Hangyi Pan, Li Zheng, Brian Armstrong, Yang Peng, Guang Peng, Binhua P. Zhou, Steven T. Rosen, Binghui Shen

Molecular and Cellular Biochemistry Faculty Publications

The downregulation of the DNA damage response (DDR) enables aggressive tumors to achieve uncontrolled proliferation against replication stress, but the mechanisms underlying this process in tumors are relatively complex. Here, we demonstrate a mechanism through which a distinct E3 ubiquitin ligase, ITCH, modulates DDR machinery in triple-negative breast cancer (TNBC). We found that expression of a nuclear form of ITCH was significantly increased in human TNBC cell lines and tumor specimens. Phosphorylation of ITCH at Ser257 by AKT led to the nuclear localization of ITCH and ubiquitination of H1.2. The ITCH-mediated polyubiquitination of H1.2 suppressed RNF8/RNF168-dependent formation of 53BP1 foci, …

Potential Applications Of Capsaicinoids In Small Cell Lung Cancer Therapy, Jamie Rae Friedman

Theses, Dissertations and Capstones

Lung cancer continues to be the leading cause of cancer related mortality worldwide. Lung cancer is not a single disease but an umbrella that encompasses two major classifications, nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC). SCLC represents about 15- 20% of all lung cancer cases and is almost exclusively diagnosed in smokers. Typically, patients will respond very well to first line treatment, but face inevitable relapse. The fact that SCLC still carries a grim 5-year survival rate of less than 5% highlights the lack of advancement in treatment options to effectively improve patient response and survival. …

An Ensemble Of Flexible Conformations Underlies Mechanotransduction By The Cadherin–Catenin Adhesion Complex, Martin Bush, Bashir M. Alhanshali, Shuo Qian, Christopher B. Stanley, William T. Heller, Tsutomu Matsui, Thomas M. Weiss, Iain D. Nicholl, Thomas Walz, David J. E. Callaway, Zimei Bu

Publications and Research

The cadherin–catenin adhesion complex is the central component of the cell–cell adhesion adherens junctions that transmit mechanical stress from cell to cell. We have determined the nanoscale structure of the adherens junction complex formed by the α-catenin•β-catenin•epithelial cadherin cytoplasmic domain (ABE) using negative stain electron microscopy, small-angle X-ray scattering, and selective deuteration/small-angle neutron scattering. The ABE complex is highly pliable and displays a wide spectrum of flexible structures that are facilitated by protein-domain motions in α- and β-catenin. Moreover, the 107-residue intrinsically disordered N-terminal segment of β-catenin forms a flexible “tongue” that is inserted into α-catenin and participates in the …

Inhibition Of Cancer Stem Cells By Glycosaminoglycan Mimetics, Connor P. O'Hara

Theses and Dissertations

Connor O’Hara July 29, 2019

Inhibition of Cancer Stem Cells by Glycosaminoglycan Mimetics

In the United States cancer is the second leading cause of death, with colorectal cancer (CRC) being the third deadliest cancer and expected to cause over 51,000 fatalities in 2019 alone.¹ The current standard of care for CRC depends largely on the staging, location, and presence of metastasis.² As the tumor grows and invades nearby lymph tissue and blood vessels, CRC has the opportunity to invade not only nearby tissue but also metastasize into the liver and lung (most commonly).³ The 5-year survival rate …

Mesenchymal Stromal Cell Therapeutic Delivery: Translational Challenges To Clinical Application, Henry Caplan, Scott D Olson, Akshita Kumar, Mitchell George, Karthik S Prabhakara, Pamela Wenzel, Supinder Bedi, Naama E Toledano-Furman, Fabio Triolo, Julian Kamhieh-Milz, Guido Moll, Charles S Cox

Faculty, Staff and Student Publications

For several decades, multipotent mesenchymal stromal cells (MSCs) have been extensively studied for their therapeutic potential across a wide range of diseases. In the preclinical setting, MSCs demonstrate consistent ability to promote tissue healing, down-regulate excessive inflammation and improve outcomes in animal models. Several proposed mechanisms of action have been posited and demonstrated across an array of in vitro models. However, translation into clinical practice has proven considerably more difficult. A number of prominent well-funded late-phase clinical trials have failed, thus calling out for new efforts to optimize product delivery in the clinical setting. In this review, we discuss novel …