Digital Commons Network^™

Cdk Inhibitors (P16/P19/P21) Induce Senescence And Autophagy In Cancer-Associated Fibroblasts, "Fueling" Tumor Growth Via Paracrine Interactions, Without An Increase In Neo-Angiogenesis., Claudia Capparelli, Barbara Chiavarina, Diana Whitaker-Menezes, Timothy G Pestell, Richard Pestell, James Hulit, Sebastiano Andò, Anthony Howell, Ubaldo E. Martinez-Outshoorn, Federica Sotgia, Michael P. Lisanti

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Here, we investigated the compartment-specific role of cell cycle arrest and senescence in breast cancer tumor growth. For this purpose, we generated a number of hTERT-immortalized senescent fibroblast cell lines overexpressing CDK inhibitors, such as p16(INK4A), p19(ARF) or p21(WAF1/CIP1). Interestingly, all these senescent fibroblast cell lines showed evidence of increased susceptibility toward the induction of autophagy (either at baseline or after starvation), as well as significant mitochondrial dysfunction. Most importantly, these senescent fibroblasts also dramatically promoted tumor growth (up to ~2-fold), without any comparable increases in tumor angiogenesis. Conversely, we generated human breast cancer cells (MDA-MB-231 cells) overexpressing CDK inhibitors, …

Medical Tourism: Trends And Opportunities, Krista Wendt

UNLV Theses, Dissertations, Professional Papers, and Capstones

Medical tourism involves travel for the purpose of receiving medical, dental, or surgical care (Medical Tourism Association), and represents a rapidly growing niche market within the healthcare, tourism, and hospitality industries. Medical travelers are motivated to seek care outside of their area of residence by many factors, including more advanced technology, quicker access, higher quality of care, or lower costs for care in the destination locality (Ehrbeck, Guevara, & Mango, 2008). Multiple factors contribute to the growth of the medical tourism industry and suggest a continuing trend toward growth in the future. This nascent industry represents a significant market opportunity …

Immune Clearance Of Attenuated Rabies Virus Results In Neuronal Survival With Altered Gene Expression., Emily A Gomme, Christoph Wirblich, Sankar Addya, Glenn F Rall, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

Rabies virus (RABV) is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. The precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. Analysis of human brains post-mortem reveals surprisingly little tissue damage and neuropathology considering the dramatic clinical symptomology, supporting the neuronal dysfunction model. However, whether or not neurons survive infection and clearance and, provided they do, whether they are functionally restored to their pre-infection phenotype has not been determined in vivo for RABV, or any neurotropic virus. This is due, in part, …

Pediatric Pharmacogenomics: A Systematic Assessment Of Ontogeny And Genetic Variation To Guide The Design Of Statin Studies In Children., Jonathan B. Wagner, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

The dose-exposure-response relationship for drugs may differ in pediatric patients compared with adults. Many clinical studies have established drug dose-exposure relationships across the pediatric age spectrum; however, genetic variation was seldom included. This article applies a systematic approach to determine the relative contribution of development and genetic variation on drug disposition and response using HMG-CoA reductase inhibitors as a model. Application of the approach drives the collection of information relevant to understanding the potential contribution of ontogeny and genetic variation to statin dose-exposure-response in children, and identifies important knowledge deficits to be addressed through the design of future studies.

Doxycycline Does Not Influence Established Abdominal Aortic Aneurysms In Angiotensin Ii-Infused Mice, Xiaojie Xie, Hong Lu, Jessica J. Moorleghen, Deborah A. Howatt, Debra L. Rateri, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Background: There is no proven medical approach to attenuating expansion and rupture of abdominal aortic aneurysms (AAAs). One approach that is currently being investigated is the use of doxycycline. Despite being primarily used as an antimicrobial drug, doxycycline has been proposed to function in reducing AAA expansion. Doxycycline is effective in reducing the formation in the most commonly used mouse models of AAAs when administered prior to the initiation of the disease. The purpose of the current study was to determine the effects of doxycycline on established AAAs when it was administered at a dose that produces therapeutic serum …

Latexin Is Down-Regulated In Hematopoietic Malignancies And Restoration Of Expression Inhibits Lymphoma Growth, Yi Liu, Dianna Howard, Kyle Rector, Carol Swiderski, Jason Brandon, Lawrence Schook, Jayesh Mehta, J. Scott Bryson, Subbarao Bondada, Ying Liang

Internal Medicine Faculty Publications

Latexin is a negative regulator of hematopoietic stem cell number in mice. Its dysregulated expression in other tumors led us to hypothesize that latexin may have tumor suppressor properties in hematological malignancies. We found that latexin was down-regulated in a variety of leukemia and lymphoma cell lines as well as in CD34+ cells from the blood and marrow of patients with these malignancies. 5-aza-2'-deoxycytodine treatment and bisulfite sequencing revealed hypermethylation of latexin promoter in tumor cells. Retrovirus-mediated latexin overexpression in A20 mouse lymphoma cells inhibited their in vitro growth by 16 fold and in vivo tumor volume by 2 fold. …

Metabolic Remodeling Of The Tumor Microenvironment: Migration Stimulating Factor (Msf) Reprograms Myofibroblasts Toward Lactate Production, Fueling Anabolic Tumor Growth., Valentina Carito, Gloria Bonuccelli, Ubaldo E Martinez-Outschoorn, Diana Whitaker-Menezes, Maria Cristina Caroleo, Erika Cione, Anthony Howell, Richard G Pestell, Michael P. Lisanti, Federica Sotgia

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Migration stimulating factor (MSF) is a genetically truncated N-terminal isoform of fibronectin that is highly expressed during mammalian development in fetal fibroblasts, and during tumor formation in human cancer-associated myofibroblasts. However, its potential functional role in regulating tumor metabolism remains unexplored. Here, we generated an immortalized fibroblast cell line that recombinantly overexpresses MSF and studied their properties relative to vector-alone control fibroblasts. Our results indicate that overexpression of MSF is sufficient to confer myofibroblastic differentiation, likely via increased TGF-b signaling. In addition, MSF activates the inflammation-associated transcription factor NFκB, resulting in the onset of autophagy/mitophagy, thereby driving glycolytic metabolism (L-lactate …

Role Of Autophagy In The Response Of Hs578t Breast Tumor Cells To Radiation, Shweta Chakradeo

Theses and Dissertations

Breast cancer is the most commonly observed cancer type in women and is the second leading cause of cancer death in women. Radiation can be used to debulk tumors prior to surgery as well as to treat patients after surgery and/or chemotherapy. Previous studies from our laboratory have shown that the anti –malarial drug chloroquine sensitizes breast cancer cell lines to radiation by suppression of autophagy which is a conservative catabolic process that can be cytoprotective. The scientific literature has demonstrated that many tumor cell systems undergo cytoprotective autophagy and that pharmacological or genetic inhibition of autophagy leads to other …

Expression Of Muc17 Is Regulated By Hif1Α-Mediated Hypoxic Responses And Requires A Methylation-Free Hypoxia Responsible Element In Pancreatic Cancer., Sho Kitamoto, Seiya Yokoyama, Michiyo Higashi, Norishige Yamada, Shyuichiro Matsubara, Sonshin Takao, Surinder K. Batra, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

MUC17 is a type 1 membrane-bound glycoprotein that is mainly expressed in the digestive tract. Recent studies have demonstrated that the aberrant overexpression of MUC17 is correlated with the malignant potential of pancreatic ductal adenocarcinomas (PDACs); however, the exact regulatory mechanism of MUC17 expression has yet to be identified. Here, we provide the first report of the MUC17 regulatory mechanism under hypoxia, an essential feature of the tumor microenvironment and a driving force of cancer progression. Our data revealed that MUC17 was significantly induced by hypoxic stimulation through a hypoxia-inducible factor 1α (HIF1α)-dependent pathway in some pancreatic cancer cells (e.g., …

Hyperpolarized 3he And 129xe Mr Imaging In Healthy Volunteers And Patients With Chronic Obstructive Pulmonary Disease, Miranda Kirby, Sarah Svenningsen, Amir Owrangi, Andrew Wheatley, Adam Farag, Alexei Ouriadov, Giles E Santyr, Roya Etemad-Rezai, Harvey O Coxson, David G Mccormack, Grace Parraga

Medical Biophysics Publications

PURPOSE: To quantitatively compare hyperpolarized helium 3 (3He) and xenon 129 (129Xe) magnetic resonance (MR) images obtained within 5 minutes in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to evaluate the correlations between 3He and 129Xe MR imaging measurements and those from spirometry and plethysmography.

MATERIALS AND METHODS: This study was approved by an ethics board and compliant with HIPAA. Written informed consent was obtained from all subjects. Eight healthy volunteers and 10 patients with COPD underwent MR imaging, spirometry, and plethysmography. Ventilation defect percentages (VDPs) at 3He and 129Xe imaging were obtained by using semiautomated …

Phthalate Exposure Changes The Metabolic Profile Of Cardiac Muscle Cells, Nikki G. Posnack, Luther M. Swift, Matthew W. Kay, Norman H. Lee, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

Background: Phthalates are common plasticizers present in medical-grade plastics and other everyday products. They can also act as endocrine-disrupting chemicals and have been linked to the rise in metabolic disorders. However, the effect of phthalates on cardiac metabolism remains largely unknown.

Objectives: We examined the effect of di(2-ethylhexyl)phthalate (DEHP) on the metabolic profile of cardiomyocytes because alterations in metabolic processes can lead to cell dysfunction.

Methods: Neonatal rat cardiomyocytes were treated with DEHP at a concentration and duration comparable to clinical exposure (50–100 μg/mL, 72 hr). We assessed the effect of DEHP on gene expression using microarray analysis. Physiological responses …

Oxygen Glucose Deprivation In Rat Hippocampal Slice Cultures Results In Alterations In Carnitine Homeostasis And Mitochondrial Dysfunction, Thomas Rau, Qing Lu, Shruti Sharma, Xutong Sun, Gregory Leary, Matthew L. Beckman, Yal Hou, Mark S. Wainwright, Michael P. Kavanaugh, David J. Poulsen, Stephen M. Black

Biomedical and Pharmaceutical Sciences Faculty Publications

Mitochondrial dysfunction characterized by depolarization of mitochondrial membranes and the initiation of mitochondrial-mediated apoptosis are pathological responses to hypoxia-ischemia (HI) in the neonatal brain. Carnitine metabolism directly supports mitochondrial metabolism by shuttling long chain fatty acids across the inner mitochondrial membrane for beta-oxidation. Our previous studies have shown that HI disrupts carnitine homeostasis in neonatal rats and that L-carnitine can be neuroprotective. Thus, this study was undertaken to elucidate the molecular mechanisms by which HI alters carnitine metabolism and to begin to elucidate the mechanism underlying the neuroprotective effect of L-carnitine (LCAR) supplementation. Utilizing neonatal rat hippocampal slice cultures we …

Herpes Simplex Virus 34.5 Interferes With Autophagosome Maturation And Antigen Presentation In Dendritic Cells, Philipe A. M. Gobeil, David A. Leib

Dartmouth Scholarship

The cellular autophagy response induced by herpes simplex virus 1 (HSV-1) is countered by the viral γ34.5 protein. γ34.5 modulates autophagy by binding to the host autophagy protein Beclin-1 and through this binding inhibits the formation of autophagosomes in fibroblasts and neurons. In contrast, in this study dendritic cells (DCs) infected with HSV-1 showed an accumulation of autophagosomes and of the long-lived protein p62. No such accumulations were observed in DCs infected with a γ34.5-null virus or a virus lacking the Beclin-binding domain (BBD) of γ34.5. To explore this further, we established stably transduced DC lines to show that γ34.5 …

Exosome-Mediated Shuttling Of Microrna-29 Regulates Hiv Tat And Morphine-Mediated Neuronal Dysfunction., Guoku Hu, H Yao, A D. Chaudhuri, Sowmya V. Yelamanchili, H Wen, P D. Cheney, Howard S. Fox, Shilpa J. Buch

Journal Articles: Pharmacology & Experimental Neuroscience

Neuronal damage is a hallmark feature of HIV-associated neurological disorders (HANDs). Opiate drug abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Opiates such as morphine have been shown to enhance HIV transactivation protein Tat-mediated toxicity in both human neurons and neuroblastoma cells. In the present study, we demonstrate reduced expression of the tropic factor platelet-derived growth factor (PDGF)-B with a concomitant increase in miR-29b in the basal ganglia region of the brains of morphine-dependent simian immunodeficiency virus (SIV)-infected macaques compared with the SIV-infected controls. In vitro relevance …

Il-1Β Amplification Of Nitric Oxide Production And Its Inhibitory Effects On Glucose Induced Early Growth Response-1 Expression In Ins-1 Cells, Ada Young

Electronic Theses and Dissertations

The pathophysiology of cytokines released by infiltrating white blood cells upon pancreatic beta cells is not fully understood. Early growth response gene-1 (Egr-1) expression is specifically and transiently up regulated in pancreatic beta cells in response to glucose. We hypothesized that interleukin-1 beta (IL-1▀) induction of nitric oxide alters glucose induced Egr-1 transcription levels. Egr-1 levels were assessed via western blot, nitric oxide was measured with a Griess Reagent kit and insulin levels via ELISA. Glucose induced both insulin and Egr-1 production in INS-1 cells. IL-1▀ dose dependently increased nitric oxide production over time and significantly attenuated glucose induced Egr-1 …

Virus-Producing Cells Determine The Host Protein Profiles Of Hiv-1 Virion Cores, Steven Santos, Yuri Obukhov, Sergei Nekhai, Michael Bukrinsky, Sergey Iordanskiy

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Upon HIV entry into target cells, viral cores are released and rearranged into reverse transcription complexes (RTCs), which support reverse transcription and also protect and transport viral cDNA to the site of integration. RTCs are composed of viral and cellular proteins that originate from both target and producer cells, the latter entering the target cell within the viral core. However, the proteome of HIV-1 viral cores in the context of the type of producer cells has not yet been characterized.

Results

We examined the proteomic profiles of the cores purified from HIV-1 NL4-3 virions assembled in Sup-T1 cells (T …

The Crispr/Cas Adaptive Immune System Of Pseudomonas Aeruginosa Mediates Resistance To Naturally Occurring And Engineered Phages, Kyle C. Cady, Joe Bondy-Denomy, Gary E. Heussler, Alan R. Davidson, George A. O'Toole

Dartmouth Scholarship

Here we report the isolation of 6 temperate bacteriophages (phages) that are prevented from replicating within the laboratory strain Pseudomonas aeruginosa PA14 by the endogenous CRISPR/Cas system of this microbe. These phages are only the second identified group of naturally occurring phages demonstrated to be blocked for replication by a nonengineered CRISPR/Cas system, and our results provide the first evidence that the P. aeruginosa type I-F CRISPR/Cas system can function in phage resistance. Previous studies have highlighted the importance of the protospacer adjacent motif (PAM) and a proximal 8-nucleotide seed sequence in mediating CRISPR/Cas-based immunity. Through engineering of a protospacer …

Interactome-Wide Analysis Identifies End-Binding Protein 1 As A Crucial Component For The Speck-Like Particle Formation Of Activated Absence In Melanoma 2 (Aim2) Inflammasomes, Li-Jie Wang, Chia-Wei Hsu, Chiu-Chin Chen, Ying Liang, Lih-Chyang Chen, David M. Ojcius, Ngan-Ming Tsang, Chuen Hsueh, Chih-Ching Wu, Yu-Sun Chang

All Dugoni School of Dentistry Faculty Articles

Inflammasomes are cytoplasmic receptors that can recognize intracellular pathogens or danger signals and are critical for interleukin 1β production. Although several key components of inflammasome activation have been identified, there has not been a systematic analysis of the protein components found in the stimulated complex. In this study, we used the isobaric tags for relative and absolute quantification approach to systemically analyze the interactomes of the NLRP3, AIM2, and RIG-I inflammasomes in nasopharyngeal carcinoma cells treated with specific stimuli of these interactomes (H2O2, poly (dA:dT), and EBV noncoding RNA, respectively). We identified a number of proteins that appeared to be …

Minor Pilins Of The Type Iv Pilus System Participate In The Negative Regulation Of Swarming Motility, S L. Kuchma, E. F. Griffin, G. A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa exhibits distinct surface-associated behaviors, including biofilm formation, flagellum-mediated swarming motility, and type IV pilus-driven twitching. Here, we report a role for the minor pilins, PilW and PilX, components of the type IV pilus assembly machinery, in the repression of swarming motility. Mutating either the pilW or pilX gene alleviates the inhibition of swarming motility observed for strains with elevated levels of the intracellular signaling molecule cyclic di-GMP (c-di-GMP) due to loss of BifA, a c-di-GMP-degrading phosphodiesterase. Blocking PilD peptidase-mediated processing of PilW and PilX renders the unprocessed proteins defective for pilus assembly but still functional in c-di-GMP-mediated swarming …

Reversal By Rarα Agonist Am580 Of C-Myc-Induced Imbalance In Rarα/Rarγ Expression During Mmtv-Myc Tumorigenesis, Almudena Bosch, Silvina P. Bertran, Yongke Lu, Avalon Garcia, Alexis M. Jones, Marcia I. Dawson, Eduardo F. Farias

Pharmacology, Physiology and Toxicology

Introduction

Retinoic acid signaling plays key roles in embryonic development and in maintaining the differentiated status of adult tissues. Recently, the nuclear retinoic acid receptor (RAR) isotypes α, β and γ were found to play specific functions in the expansion and differentiation of the stem compartments of various tissues. For instance, RARγ appears to be involved in stem cell compartment expansion, while RARα and RARβ are implicated in the subsequent cell differentiation. We found that over-expressing c-Myc in normal mouse mammary epithelium and in a c-Myc-driven transgenic model of mammary cancer, disrupts the balance between RARγ and RARα/β in …

Development Of Dna Vaccination Approach For Tumor Immunotargeting, Nathaniel Sangster

Summer Training Program in Cancer Immunotherapy

The emergence of immunotherapy as a prominent modality to treat cancer is a crucial advancement in the fight against this devastating disease. Although DNA vaccines against cancer have not been effective in treating pre-existing tumors, this approach holds much promise particularly for the activation of immune responses to specific mutant antigens responsible for tumorigenesis. Recent studies demonstrated that Q209L point mutation in the GNAQ (and GNA11) is responsible for the development of more than 70% of uveal melanomas and pre-malignant cutaneous blue nevus in humans. Based on the epitope prediction, we hypothesized that DNA vaccination with mutant GNAQ may result …

Weaponizing Tear Gas: Bahrain’S Unprecedented Use Of Toxic Chemical Agents Against Civilians., Richard Sollom, Holly G. Atkinson

Publications and Research

The Bahraini government’s response to the early 2011 pro-democracy protests was brutal, systematic, and violent. In addition to birdshot and rubber bullets, government law enforcement attacked unarmed protestors with toxic chemical agents including tear gas. The government’s crackdown on the medical profession was especially harmful, as security forces arrested and detained doctors, raided health facilities, and obstructed patients from receiving necessary care. This report’s findings are based on field research that the authors conducted in Bahrain (April 2012) to investigate excessive use of force by law enforcement officials since June 2011—the end of Bahrain’s state of emergency. The medico-legal team …

Reactions Of Methyl Perfluoroalkyl Ethers With Isopropyl Alcohol: Experimental And Theoretical Studies, Howard Knachel, Vladimir Benin, Chadwick Barklay, Janine C. Birkbeck, Billy D. Faubion, William E. Moddeman

Chemistry Faculty Publications

The reaction of an isomeric mixture of the methyl perfluoroalkyl ether, C4F9OCH3 (Novec-7100), in the presence of isopropyl alcohol (IPA) and/or water has been studied by measuring the rate of product formation using an ion-selective electrode (ISE) for fluoride ion, Karl Fisher coulometric titrations for water, and 1H and 19F NMR spectroscopy for product identification and rate studies. The results showed the methyl perfluoroalkyl ether to be very stable with products forming at the rate of ∼1 ppm per year at a laboratory temperature of 20 °C. Measurements over the temperature range of 6° to 100 °C were made on …

Assessing Blood Culture Contamination, Deborah Harris

OTS Master's Level Projects & Papers

The problem of this study was to evaluate blood culture collection procedures utilized at the study hospital to determine the cause of the high contamination rates.

Exogenous Alpha-Synuclein Induces Cell Death Related Proteins In C6 Oligodendrocyte-Like Cells Corresponding To Protein Expression Observed In Multiple System Atrophy, Derrick Samuel Hilton

Dissertations

Multiple System Atrophy (MSA) consists of three disorders; Autonomic Dysfunction, Cerebellar Ataxia, and Parkinsonism. In MSA, the protein Alpha-Synuclein (SNCA) appears in the central nervous system as misfolded protein aggregates primarily in oligodendrocytes. This dissertation reports the results from studies examining the effect of exogenous SNCA has on a cell model: C6 oligodendrocyte-like cells. Treated cells were evaluated using western blot and DNA microarray. In addition the expression of proteins was evaluated using immunocytochemistry in MSA patient tissue.

C6 cells were shown to take up SNCA when added to the media. SNCA also underwent a truncation when taken up by …

The New Role Of Proprotein Convertase Subtilisin/Kexin Type 9: A Connection Of Proprotein Convertase Subtilisin/Kexin Type 9, Apolipoprotein B, And Autophagy, Hua Sun

Dissertations and Theses (Open Access)

Plasma low-density lipoprotein (LDL) levels are positively correlated with the incidence of coronary artery disease. In the circulation, the plasma LDL clearance is mainly achieved by the uptake via LDL receptor (LDLR). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a newly discovered gene, playing an important role in LDL metabolism. Gain-of-function mutations of PCSK9 lead to hypercholesterolemia and loss-of-function mutations of PCSK9 are associated with decrease of LDL cholesterol. The effects of PCSK9 on cholesterol levels are the consequence of a strong interaction between the catalytic domain of PCSK9 and epidermal growth factor-like repeat A (EGF-A) domain of …

Direct Effects Of Metformin On Pi3k And Ras Signaling In Endometrial Cancer, David A. Iglesias M.D.

Dissertations and Theses (Open Access)

Metformin has antiproliferative effects through the activation of AMPK and has gained interest as an antineoplastic agent in several cancer types, although studies in endometrial cancer (EC) are limited. The aims of this project were to evaluate pathways targeted by metformin in EC, investigate mechanisms by which metformin exerts its antiproliferative effects, and explore rational combination therapies with other targeted agents.

Three EC cell lines were used to evaluate metformin’s effect on cell proliferation, PI3K and Ras-MAPK signaling, and apoptosis. A xenograft mouse model was also used to evaluate the effects of metformin treatment on in vivo tumor growth. These …

Measurement Of The Oxidation State Of Mitochondrial Cytochrome C From The Neocortex Of The Mammalian Brain, Y. Sakata, M. Abajian, M. O. Ripple, R. Springett

Dartmouth Scholarship

Diffuse optical remission spectra from the mammalian neocortex at visible wavelengths contain spectral features originating from the mitochondria. A new algorithm is presented, based on analytically relating the first differential of the attenuation spectrum to the first differential of the chromophore spectra, that can separate and calculate the oxidation state of cytochrome c as well as the absolute concentration and saturation of hemoglobin. The algorithm is validated in phantoms and then tested on the neocortex of the rat during an anoxic challenge. Implementation of the algorithm will provide detailed information of mitochondrial oxygenation and mitochondrial function in physiological studies of …

Secreted Semaphorin 5a Suppressed Pancreatic Tumour Burden But Increased Metastasis And Endothelial Cell Proliferation., A Sadanandam, S S. Sidhu, S Wullschleger, S Singh, M L. Varney, C-S Yang, A E. Ashour, Surinder K. Batra, Rakesh Singh

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Our earlier reports demonstrated that membrane-bound semaphorin 5A (SEMA5A) is expressed in aggressive pancreatic cancer cells and tumours, and promotes tumour growth and metastasis. In this study, we examine whether (1) pancreatic cancer cells secrete SEMA5A and (2) that secreted SEMA5A modulates certain phenotypes associated with tumour progression, angiogenesis and metastasis through various other molecular factors and signalling proteins.

METHODS AND RESULTS: In this study, we show that human pancreatic cancer cell lines secrete the extracellular domain (ECD) of SEMA5A (SEMA5A-ECD) and overexpression of mouse Sema5A-ECD in Panc1 cells (not expressing SEMA5A; Panc1-Sema5A-ECD; control cells - Panc1-control) significantly increases …

The Anti-Tumorigenic Mushroom Agaricus Blazei Murill Enhances Il-1Β Production And Activates The Nlrp3 Inflammasome In Human Macrophages, Tsung-Teng Huang, David M. Ojcius, John Ding-E. Young, Yi-Hui Wu, Yun-Fei Ko, Tsui-Yin Wong, Cheng-Yeu Wu, Chia-Chen Lu, Hsin-Chih Lai

All Dugoni School of Dentistry Faculty Articles

Agaricus blazei Murill (AbM) has been reported to possess immune activity against tumors and infections through stimulation of mononuclear phagocytes. Recently, AbM extract was shown to induce the production of the pro-inflammatory cytokine, interleukin-1β (IL-1β), in human monocytes. IL-1β is a key pro-inflammatory cytokine produced by activated macrophages and monocytes and its secretion is strictly controlled by the inflammasome. The purpose of this study is to investigate the effect of AbM water extracts on the regulation of IL-1β production and activation of the NLRP3 inflammasome in human THP-1 macrophages. The NLRP3 inflammasome consists of an NLRP3 receptor, an adaptor protein …