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Full-Text Articles in Medicine and Health Sciences
Glypican-1 Modulates The Angiogenic And Metastatic Potential Of Human And Mouse Cancer Cells, Takuma Aikawa, Chery A. Whipple, Martha E. Lopez, Jason Gunn, Alison Young, Arthur D. Lander, Murray Korc
Glypican-1 Modulates The Angiogenic And Metastatic Potential Of Human And Mouse Cancer Cells, Takuma Aikawa, Chery A. Whipple, Martha E. Lopez, Jason Gunn, Alison Young, Arthur D. Lander, Murray Korc
Dartmouth Scholarship
Cells isolated from many types of human cancers express heparin-binding growth factors (HBGFs) that drive tumor growth, metastasis, and angiogenesis. The heparan sulfate proteoglycan glypican-1 (GPC1) is a coreceptor for HBGFs. Here we show that both cancer cell–derived and host-derived GPC1 are crucial for efficient growth, metastasis, and angiogenesis of human and mouse cancer cells. Thus downregulation of GPC1 in the human pancreatic cancer cell line PANC-1, using antisense approaches, resulted in prolonged doubling times and decreased anchorage-independent growth in vitro as well as attenuated tumor growth, angiogenesis, and metastasis when these cells were transplanted into athymic mice. Moreover, athymic …
Retinoid X Receptor And Peroxisome Proliferator-Activated Receptor-Gamma Agonists Cooperate To Inhibit Matrix Metalloproteinase Gene Expression, Peter S. Burrage, Adam C. Schmucker, Yanqing Ren, Michael B. Sporn, Constance E. Brinckerhoff
Retinoid X Receptor And Peroxisome Proliferator-Activated Receptor-Gamma Agonists Cooperate To Inhibit Matrix Metalloproteinase Gene Expression, Peter S. Burrage, Adam C. Schmucker, Yanqing Ren, Michael B. Sporn, Constance E. Brinckerhoff
Dartmouth Scholarship
We recently described the ability of retinoid X receptor (RXR) ligand LG100268 (LG268) to inhibit interleukin-1-beta (IL-1-β)-driven matrix metalloproteinase-1 (MMP-1) and MMP-13 gene expression in SW-1353 chondrosarcoma cells. Other investigators have demonstrated similar effects in chondrocytes treated with rosiglitazone, a ligand for peroxisome proliferator-activated receptor-gamma (PPARγ), for which RXR is an obligate dimerization partner. The goals of this study were to evaluate the inhibition of IL-1--induced expression of MMP-1andMMP-13 by combinatorial treatment with RXR and PPAR ligands and to investigate the molecular mechanisms of this inhibition.
Transport Of Ldl-Derived Cholesterol From The Npc1 Compartment To The Er Involves The Trans-Golgi Network And The Snare Protein Complex, Yasuomi Urano, Hiroshi Watanabe, Stephanie R. Murphy, Yohei Shibuya, Yong Geng, Andrew Peden, Catherine Chang, Ta Yuan Chang
Transport Of Ldl-Derived Cholesterol From The Npc1 Compartment To The Er Involves The Trans-Golgi Network And The Snare Protein Complex, Yasuomi Urano, Hiroshi Watanabe, Stephanie R. Murphy, Yohei Shibuya, Yong Geng, Andrew Peden, Catherine Chang, Ta Yuan Chang
Dartmouth Scholarship
Mammalian cells acquire cholesterol mainly from LDL. LDL enter the endosomes, allowing cholesteryl esters to be hydrolyzed by acid lipase. The hydrolyzed cholesterol (LDL-CHOL) enters the Niemann-Pick type C1 (NPC1)-containing endosomal compartment en route to various destinations. Whether the Golgi is involved in LDL-CHOL transport downstream of the NPC1 compartment has not been demonstrated. Using subcellular fractionation and immunoadsorption to enrich for specific membrane fractions, here we show that, when parental Chinese hamster ovary (CHO) cells are briefly exposed to (3)H-cholesteryl linoleate (CL) labeled-LDL, newly liberated (3)H-LDL-CHOL appears in membranes rich in trans-Golgi network (TGN) long before it becomes available …
Identification Of Two Gene Clusters And A Transcriptional Regulator Required For Pseudomonas Aeruginosa Glycine Betaine Catabolism, Matthew J. Wargo, Benjamin S. Szwergold, Deborah A. Hogan
Identification Of Two Gene Clusters And A Transcriptional Regulator Required For Pseudomonas Aeruginosa Glycine Betaine Catabolism, Matthew J. Wargo, Benjamin S. Szwergold, Deborah A. Hogan
Dartmouth Scholarship
Glycine betaine (GB), which occurs freely in the environment and is an intermediate in the catabolism of choline and carnitine, can serve as a sole source of carbon or nitrogen in Pseudomonas aeruginosa. Twelve mutants defective in growth on GB as the sole carbon source were identified through a genetic screen of a nonredundant PA14 transposon mutant library. Further growth experiments showed that strains with mutations in two genes, gbcA (PA5410) and gbcB (PA5411), were capable of growth on dimethylglycine (DMG), a catabolic product of GB, but not on GB itself. Subsequent nuclear magnetic resonance (NMR) experiments with 1,2-(13)C-labeled choline …
Mgra Represses Biofilm Formation In Staphylococcus Aureus, Maria P. Trotonda, Sandeep Tamber, Guido Memmi, Ambrose L. Cheung
Mgra Represses Biofilm Formation In Staphylococcus Aureus, Maria P. Trotonda, Sandeep Tamber, Guido Memmi, Ambrose L. Cheung
Dartmouth Scholarship
MgrA is a pleiotropic regulator that controls autolysis, virulence, and efflux pump activity in Staphylococcus aureus. We recently found that mgrA mutants of strains RN6390, SH1000, and MW2 also displayed enhanced biofilm formation compared with their respective parents. The biofilms formed by mgrA mutants of RN6390 and MW2 are independent of sigB and ica loci, two genetic elements that have been previously associated with biofilm formation in S. aureus. Biofilms formed by mgrA mutants are dependent on the expression of surface proteins mediated by the sortase gene srtA. Extracellular DNA was also a crucial component of the early biofilm of …
The Fgf System Has A Key Role In Regulating Vascular Integrity, Masahiro Murakami, Loc T. Nguyen, Zhen W. Zhang, Karen L. Moodie, Pater Carmellet, Radu V. Stan, Michael Simons
The Fgf System Has A Key Role In Regulating Vascular Integrity, Masahiro Murakami, Loc T. Nguyen, Zhen W. Zhang, Karen L. Moodie, Pater Carmellet, Radu V. Stan, Michael Simons
Dartmouth Scholarship
The integrity of the endothelial monolayer is essential to blood vessel homeostasis and active regulation of endothelial permeability. The FGF system plays important roles in a wide variety of physiologic and pathologic conditions; however, its role in the adult vasculature has not been defined. To assess the role of the FGF system in the adult endothelial monolayer, we disrupted FGF signaling in bovine aortic endothelial cells and human saphenous vein endothelial cells in vitro and in adult mouse and rat endothelial cells in vivo using soluble FGF traps or a dominant inhibitor of all FGF receptors. The inhibition of FGF …
The Bile Response Repressor Brer Regulates Expression Of The Vibrio Cholerae Breab Efflux System Operon, Francisca A. Cerda-Maira, Carol S. Ringelberg, Ronald K. Taylor
The Bile Response Repressor Brer Regulates Expression Of The Vibrio Cholerae Breab Efflux System Operon, Francisca A. Cerda-Maira, Carol S. Ringelberg, Ronald K. Taylor
Dartmouth Scholarship
Enteric pathogens have developed several resistance mechanisms to survive the antimicrobial action of bile. We investigated the transcriptional profile of Vibrio cholerae O1 El Tor strain C6706 under virulence gene-inducing conditions in the presence and absence of bile. Microarray analysis revealed that the expression of 119 genes was affected by bile. The mRNA levels of genes encoding proteins involved in transport were increased in the presence of bile, whereas the mRNA levels of genes encoding proteins involved in pathogenesis and chemotaxis were decreased. This study identified genes encoding transcriptional regulators from the TetR family (vexR and breR) and …
Direct Estimation Of Evoked Hemoglobin Changes By Multimodality Fusion Imaging, Theodore J. Huppert, Solomon G. Diamond, David A. Boas
Direct Estimation Of Evoked Hemoglobin Changes By Multimodality Fusion Imaging, Theodore J. Huppert, Solomon G. Diamond, David A. Boas
Dartmouth Scholarship
In the last two decades, both diffuse optical tomography (DOT) and blood oxygen level dependent (BOLD)-based functional magnetic resonance imaging (fMRI) methods have been developed as noninvasive tools for imaging evoked cerebral hemodynamic changes in studies of brain activity. Although these two technologies measure functional contrast from similar physiological sources, i.e., changes in hemoglobin levels, these two modalities are based on distinct physical and biophysical principles leading to both limitations and strengths to each method. In this work, we describe a unified linear model to combine the complimentary spatial, temporal, and spectroscopic resolutions of concurrently measured optical tomography and fMRI …
Staphylococcus Aureus Pbp4 Is Essential For Β-Lactam Resistance In Community-Acquired Methicillin-Resistant Strains, G Memmi, S R. Filipe, M G. Pinho, Z Fu, Ambrose Cheung
Staphylococcus Aureus Pbp4 Is Essential For Β-Lactam Resistance In Community-Acquired Methicillin-Resistant Strains, G Memmi, S R. Filipe, M G. Pinho, Z Fu, Ambrose Cheung
Dartmouth Scholarship
Recent cases of infections caused by community-acquired methicillin-resistant Staphylococcus aureus (MRSA) (CA-MRSA) strains in healthy individuals have raised concerns worldwide. CA-MRSA strains differ from hospital-acquired MRSAs by virtue of their genomic background and increased virulence in animal models.
The Synthetic Triterpenoid Cddo-Methyl Ester Modulates Microglial Activities, Inhibits Tnf Production, And Provides Dopaminergic Neuroprotection, Thi A. Tran, Melissa K. Mccoy, Michael B. Sporn, Malú G. Tansey
The Synthetic Triterpenoid Cddo-Methyl Ester Modulates Microglial Activities, Inhibits Tnf Production, And Provides Dopaminergic Neuroprotection, Thi A. Tran, Melissa K. Mccoy, Michael B. Sporn, Malú G. Tansey
Dartmouth Scholarship
Recent animal and human studies implicate chronic activation of microglia in the progressive loss of CNS neurons. The inflammatory mechanisms that have neurotoxic effects and contribute to neurodegeneration need to be elucidated and specifically targeted without interfering with the neuroprotective effects of glial activities. Synthetic triterpenoid analogs of oleanolic acid, such as methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me, RTA 402) have potent anti-proliferative and differentiating effects on tumor cells, and anti-inflammatory activities on activated macrophages. We hypothesized that CDDO-Me may be able to suppress neurotoxic microglial activities while enhancing those that promote neuronal survival. Therefore, the aims of our study were to identify specific …
Cif Is Negatively Regulated By The Tetr Family Repressor Cifr, Daniel P. Maceachran, Bruce A. Stanton, George A. O'Toole
Cif Is Negatively Regulated By The Tetr Family Repressor Cifr, Daniel P. Maceachran, Bruce A. Stanton, George A. O'Toole
Dartmouth Scholarship
We previously reported that the novel Pseudomonas aeruginosa toxin Cif is capable of decreasing apical membrane expression of the cystic fibrosis transmembrane conductance regulator (CFTR). We further demonstrated that Cif is capable of degrading the synthetic epoxide hydrolase (EH) substrate S-NEPC [(2S,3S)-trans-3-phenyl-2-oxiranylmethyl 4-nitrophenol carbonate], suggesting that Cif may be reducing apical membrane expression of CFTR via its EH activity. Here we report that Cif is capable of degrading the xenobiotic epoxide epibromohydrin (EBH) to its vicinal diol 3-bromo-1,2-propanediol. We also demonstrate that this epoxide is a potent inducer of cif gene expression. We show that the predicted TetR family transcriptional …
Protoporphyrin Ix Fluorescence Photobleaching Increases With The Use Of Fractionated Irradiation In The Esophagus, Brian W.Q. Pogue, Chao Sheng, Juan Benevides, David Forcione, Bill Puricelli, Norman S. Nishioka, Tayyaba Hasan
Protoporphyrin Ix Fluorescence Photobleaching Increases With The Use Of Fractionated Irradiation In The Esophagus, Brian W.Q. Pogue, Chao Sheng, Juan Benevides, David Forcione, Bill Puricelli, Norman S. Nishioka, Tayyaba Hasan
Dartmouth Scholarship
Fluorescence measurements have been used to track the dosimetry of photodynamic therapy (PDT) for many years, and this approach can be especially important for treatments with aminolevulinic-acid-induced protoporphyrin IX (ALA-PpIX). PpIX photobleaches rapidly, and the bleaching is known to be oxygen dependent, and at the same time, fractionation or reduced irradiance treatments have been shown to significantly increase efficacy. Thus, in vivo measurement of either the bleaching rate and/or the total bleaching yield could be used to track the deposited dose in tissue and determine the optimal treatment plans. Fluorescence in rat esophagus and human Barrett's esophagus are measured during …
Inhibition Of Signal Transducer And Activator Of Transcription 3 Expression By Rna Interference Suppresses Invasion Through Inducing Anoikis In Human Colon Cancer Cells, Yu Fan, You-Li Zhang, Ying Wu, Wei Zhang, Yin-Huan Wang, Zhao-Ming Cheng, Hua Li
Inhibition Of Signal Transducer And Activator Of Transcription 3 Expression By Rna Interference Suppresses Invasion Through Inducing Anoikis In Human Colon Cancer Cells, Yu Fan, You-Li Zhang, Ying Wu, Wei Zhang, Yin-Huan Wang, Zhao-Ming Cheng, Hua Li
Dartmouth Scholarship
AIM: To investigate the roles and mechanism of signal transducer and activator of transcription 3 (STAT3) in invasion of human colon cancer cells by RNA interference.
Amp-Activated Protein Kinase Regulates Co2-Induced Alveolar Epithelial Dysfunction In Rats And Human Cells By Promoting Na,K-Atpase Endocytosis, István Vadász, Laura A. Dada, Arturo Briva, Humberto E. Trejo, Lynn C. Welch, Jiwang Chen, Peter T. Toth, Emilia Lecuona, Lee A. Witters, Paul T. Schumacker, Navdeep S. Chandel, Werner Seeger, Jacob I. Sznajder
Amp-Activated Protein Kinase Regulates Co2-Induced Alveolar Epithelial Dysfunction In Rats And Human Cells By Promoting Na,K-Atpase Endocytosis, István Vadász, Laura A. Dada, Arturo Briva, Humberto E. Trejo, Lynn C. Welch, Jiwang Chen, Peter T. Toth, Emilia Lecuona, Lee A. Witters, Paul T. Schumacker, Navdeep S. Chandel, Werner Seeger, Jacob I. Sznajder
Dartmouth Scholarship
Hypercapnia (elevated CO2 levels) occurs as a consequence of poor alveolar ventilation and impairs alveolar fluid reabsorption (AFR) by promoting Na,K-ATPase endocytosis. We studied the mechanisms regulating CO2-induced Na,K-ATPase endocytosis in alveolar epithelial cells (AECs) and alveolar epithelial dysfunction in rats. Elevated CO2 levels caused a rapid activation of AMP-activated protein kinase (AMPK) in AECs, a key regulator of metabolic homeostasis. Activation of AMPK was mediated by a CO2-triggered increase in intracellular Ca2+ concentration and Ca2+/calmodulin-dependent kinase kinase-β (CaMKK-β). Chelating intracellular Ca2+ or abrogating CaMKK-β function by gene silencing or …
Repression Of Hla By Rot Is Dependent On Sae In Staphylococcus Aureus, Dongmei Li, Ambrose Cheung
Repression Of Hla By Rot Is Dependent On Sae In Staphylococcus Aureus, Dongmei Li, Ambrose Cheung
Dartmouth Scholarship
The regulatory locus sae is a two-component system in Staphylococcus aureus that regulates many important virulence factors, including alpha-toxin (encoded by hla) at the transcriptional level. The SarA homologs Rot and SarT were previously shown to be repressors of hla in selected S. aureus backgrounds. To delineate the interaction of rot and sae and the contribution of sarT to hla expression, an assortment of rot and sae isogenic single mutants, a rot sae double mutant, and a rot sae sarT markerless triple mutant were constructed from wild-type strain COL. Using Northern blot analysis and transcriptional reporter gene green fluorescent protein, …