Mitochondrial oxidative phosphorylation (OXPHOS) is central to physiology and disease pathogenesis. To systematically investigate its activity and regulation, we performed a wide range of assays of OXPHOS physiology and nuclear and mitochondrial gene expression across 2490 chemical perturbations in muscle cells. Through mining of the resulting compendium, we discovered that: ... More
Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells.
JournalProceedings of the National Academy of Sciences of the United States of America
PubMed ID18334633
Embryonic stem cells sustain a microenvironment that facilitates a balance of self-renewal and differentiation. Aggressive cancer cells, expressing a multipotent, embryonic cell-like phenotype, engage in a dynamic reciprocity with a microenvironment that promotes plasticity and tumorigenicity. However, the cancer-associated milieu lacks the appropriate regulatory mechanisms to maintain a normal cellular ... More
Authors
Journal
PubMed ID11114349
Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism.
JournalNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
PubMed ID16384827
BACKGROUND: Cardiovascular disease is the most frequent cause of death in patients with end-stage kidney disease (ESKD). Vascular calcification is a confirmed risk factor for cardiovascular events in the general population and has a high occurrence in patients with ESKD. Despite the high prevalence of vascular calcification in ESKD, the ... More
Nitric oxide and AMPK cooperatively regulate PGC-1 in skeletal muscle cells.
Nitric oxide (NO) induces mitochondrial biogenesis in skeletal muscle cells via upregulation of the peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha). Further, we have shown that nitric oxide interacts with the metabolic sensor enzyme, AMPK. Therefore, we tested the hypothesis that nitric oxide and AMPK act synergistically to upregulate PGC-1alpha mRNA ... More
Effect of natural commensal-origin DNA on toll-like receptor 9 (TLR9) signaling cascade, chemokine IL-8 expression, and barrier integritiy of polarized intestinal epithelial cells.
BACKGROUND AND AIM: The intestinal epithelium is constantly exposed to high levels of genetic material like bacterial DNA. Under normal physiological conditions, the intestinal epithelial monolayer as a formidable dynamic barrier with a high-polarity structure facilitates only a controlled and selective flux on components between the lumen and the underlining ... More
Detection of differentially expressed glycogenes in trabecular meshwork of eyes with primary open-angle glaucoma.
AuthorsDiskin S,Kumar J,Cao Z,Schuman JS,Gilmartin T,Head SR,Panjwani N
PURPOSE: To identify differentially expressed glycogenes in trabecular meshwork (TM) of eyes with primary open-angle glaucoma (POAG). METHODS: Total RNA was isolated from TM of cadaveric eyes derived from donors with diagnosed glaucomas of different etiologies and from normal control subjects. RNA was amplified and hybridized to the GLYCOv2 oligonucleotide ... More
Absence of adenosine-mediated aortic relaxation in A(2A) adenosine receptor knockout mice
JournalAmerican Journal of Physiology-heart and Circulatory Physiology
PubMed ID
Ponnoth DS, Sanjani MS, Ledent C, Roush K, Krahn T, Mustafa SJ. Absence of adenosine-mediated aortic relaxation in A(2A) adenosine receptor knockout mice. Am J Physiol Heart Circ Physiol 297: H1655-H1660, 2009. First published September 11, 2009; doi:10.1152/ajpheart.00192.2009.-Adenosine mediates vascular responses through four receptor subtypes: A(1), A(2A), A(2B), and A(3). ... More
Up-regulation of Cbfa1 and Pit-1 in calcified artery of uraemic rats with severe hyperphosphataemia and secondary hyperparathyroidism.
JournalNephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
PubMed ID
BACKGROUND: Cardiovascular disease is the most frequent cause of death in patients with end-stage kidney disease (ESKD). Vascular calcification is a confirmed risk factor for cardiovascular events in the general population and has a high occurrence in patients with ESKD. Despite the high prevalence of vascular calcification in ESKD, the ... More
Presence of an established calcification marker in trabecular meshwork tissue of glaucoma donors.
AuthorsXue W; Comes N; Borras T
JournalInvestigative Ophthalmology & Visual Science
PubMed ID
PURPOSE: To determine the presence of calcification markers in the trabecular meshwork tissue from glaucoma donors and in trabecular meshwork cells insulted by dexamethasone (DEX) and transforming growth factor beta2 (TGFbeta2), factors associated with glaucoma. To investigate as well the effect of silencing the inhibitor of calcification matrix Gla (MGP) ... More
Host genetics of Bordetella pertussis infection in mice: significance of Toll-like receptor 4 in genetic susceptibility and pathobiology.
AuthorsBanus HA; Vandebriel RJ; de Ruiter H; Dormans JA; Nagelkerke NJ; Mooi FR; Hoebee B; van Kranen HJ; Kimman TG
JournalInfection and Immunity
PubMed ID
The susceptibility to and the severity of Bordetella pertussis infections in infants and children varies widely, suggesting that genetic differences between individuals influence the course of infection. We have previously identified three novel loci that influence the severity of whooping cough by using recombinant congenic strains of mice: Bordetella pertussis ... More
ADAM15 upregulation and interaction with multiple binding partners in inflammatory bowel disease.
JournalLaboratory Investigation; A Journal of Technical Methods and Pathology
PubMed ID
A disintegrin and metalloproteinase (ADAM)15 is upregulated in some tissues undergoing remodeling. This glycoprotein is characterized by adhesive function through its interaction with members of the integrin family and protease properties. The goal of this work was to describe the tissue distribution of ADAM15 and its spatial relationship with its ... More
RNA interference mediated in human primary cells via recombinant baculoviral vectors.
AuthorsNicholson LJ, Philippe M, Paine AJ, Mann DA, Dolphin CT
JournalMol Ther
PubMed ID15771966
The success of RNA interference (RNAi) in mammalian cells, mediated by siRNAs or shRNA-generating plasmids, is dependent, to an extent, upon transfection efficiency. This is a particular problem with primary cells, which are often difficult to transfect using cationic lipid vehicles. Effective RNAi in primary cells is thus best achieved ... More
Maturation of ribbon synapses in hair cells is driven by thyroid hormone.
AuthorsSendin G, Bulankina AV, Riedel D, Moser T
JournalJ Neurosci
PubMed ID17376978
Ribbon synapses of inner hair cells (IHCs) undergo developmental maturation until after the onset of hearing. Here, we studied whether IHC synaptogenesis is regulated by thyroid hormone (TH). We performed perforated patch-clamp recordings of Ca2+ currents and exocytic membrane capacitance changes in IHCs of athyroid and TH-substituted Pax8-/- mice during ... More
Fine-scale quantification of HCG beta gene transcription in human trophoblastic and non-malignant non-trophoblastic tissues.
AuthorsRull K, Hallast P, Uuskula L, Jackson J, Punab M, Salumets A, Campbell RK, Laan M
JournalMol Hum Reprod
PubMed ID18048458
Human chorionic gonadotropin (HCG) is produced by syncytiotrophoblast of placenta. It delays the apoptosis of corpus luteum and functions in implantation. Its possible role in male reproduction has been raised. HCG beta subunit is encoded by CGB, CGB5, CGB7 and CGB8 genes located at 19q13.3 in a common genome cluster ... More
Beta-Catenin mediates the anti-adipogenic effect of baicalin.
AuthorsLee H, Bae S, Kim K, Kim W, Chung SI, Yoon Y
JournalBiochem Biophys Res Commun
PubMed ID20627088
beta-Catenin reportedly inhibits adipogenesis through the down-regulations of peroxisome proliferator-activated receptor (PPAR)gamma and CCAAT/enhancer binding protein (C/EBP)alpha. We report that baicalin, a natural flavonoid compound, inhibits adipogenesis by modulating beta-Catenin. During 3T3-L1 cell adipogenesis, beta-Catenin was down-regulated, but baicalin treatment maintained beta-Catenin expression. Anti-adipogenic effects of baicalin were significantly attenuated ... More
Strain-dependent increases in retinal inflammatory proteins and photoreceptor FGF-2 expression in streptozotocin-induced diabetic rats.
AuthorsKirwin SJ, Kanaly ST, Linke NA, Edelman JL
JournalInvest Ophthalmol Vis Sci
PubMed ID19474406
PURPOSE: Inflammation is thought to play a role in disease progression and vision loss in diabetic retinopathy (DR). However, the level of inflammation and the role of cytokines and growth factors in the early stages of this disease are poorly understood. Streptozotocin (STZ)-induced hyperglycemia in rats is widely used as ... More
Lack of suppressive CD4+CD25+FOXP3+ T cells in advanced stages of primary cutaneous T-cell lymphoma.
AuthorsTiemessen MM, Mitchell TJ, Hendry L, Whittaker SJ, Taams LS, John S
JournalJ Invest Dermatol
PubMed ID16741512
Mycosis fungoides and its leukemic variant, Sezary syndrome, are the most common primary cutaneous T-cell lymphomas (CTCLs). In an ex vivo study, we investigated the percentage, phenotype, and suppressive function of CD4+CD25+ regulatory T cells (Tregs) from peripheral blood of CTCL patients. The percentage of Tregs did not differ significantly ... More
IFNgamma restores breast cancer sensitivity to fulvestrant by regulating STAT1, IFN regulatory factor 1, NF-kappaB, BCL2 family members, and signaling to caspase-dependent apoptosis.
AuthorsNing Y, Riggins RB, Mulla JE, Chung H, Zwart A, Clarke R
JournalMol Cancer Ther
PubMed ID20457620
Antiestrogens are effective therapies for the management of many estrogen receptor-alpha (ER)-positive breast cancers. Nonetheless, both de novo and acquired resistance occur and remain major problems in the clinical setting. IFNgamma is an inflammatory cytokine that induces the expression and function of IFN regulatory factor 1 (IRF1), a tumor suppressor ... More
Thiocyanate transport in resting and IL-4-stimulated human bronchial epithelial cells: role of pendrin and anion channels.
AuthorsPedemonte N, Caci E, Sondo E, Caputo A, Rhoden K, Pfeffer U, Di Candia M, Bandettini R, Ravazzolo R, Zegarra-Moran O, Galietta LJ
JournalJ Immunol
PubMed ID17404297
SCN(-) (thiocyanate) is an important physiological anion involved in innate defense of mucosal surfaces. SCN(-) is oxidized by H(2)O(2), a reaction catalyzed by lactoperoxidase, to produce OSCN(-) (hypothiocyanite), a molecule with antimicrobial activity. Given the importance of the availability of SCN(-) in the airway surface fluid, we studied transepithelial SCN(-) ... More
Expression of the CTCF-paralogous cancer-testis gene, brother of the regulator of imprinted sites (BORIS), is regulated by three alternative promoters modulated by CpG methylation and by CTCF and p53 transcription factors.
BORIS, like other members of the 'cancer/testis antigen' family, is normally expressed in testicular germ cells and repressed in somatic cells, but is aberrantly activated in cancers. To understand regulatory mechanisms governing human BORIS expression, we characterized its 5'-flanking region. Using 5' RACE, we identified three promoters, designated A, B ... More
Protein phosphatase 4 regulates apoptosis, proliferation and mutation rate of human cells.
AuthorsMourtada-Maarabouni M, Williams GT
JournalBiochim Biophys Acta
PubMed ID18424272
The proteins which regulate apoptosis are of great importance both in normal cell biological processes and in the development of pathology in the diverse diseases which involve apoptosis dysfunction. The activity of many of these proteins is controlled by reversible phosphorylation, so that the relevant kinases and phosphatases play crucial ... More
Selective clearance of macrophages in atherosclerotic plaques by autophagy.
AuthorsVerheye S, Martinet W, Kockx MM, Knaapen MW, Salu K, Timmermans JP, Ellis JT, Kilpatrick DL, De Meyer GR
JournalJ Am Coll Cardiol
PubMed ID17291937
OBJECTIVES: The purpose of this study was to investigate whether stent-based delivery of an inhibitor of mammalian target of rapamycin (mTOR) can selectively clear macrophages in rabbit atherosclerotic plaques. BACKGROUND: Current pharmacologic approaches to stabilize atherosclerotic plaques have only partially reduced the incidence of acute coronary syndromes and sudden death. ... More
Human embryonic stem cells in culture possess primary cilia with hedgehog signaling machinery.
AuthorsKiprilov EN, Awan A, Desprat R, Velho M, Clement CA, Byskov AG, Andersen CY, Satir P, Bouhassira EE, Christensen ST, Hirsch RE
JournalJ Cell Biol
PubMed ID18332216
Human embryonic stem cells (hESCs) are potential therapeutic tools and models of human development. With a growing interest in primary cilia in signal transduction pathways that are crucial for embryological development and tissue differentiation and interest in mechanisms regulating human hESC differentiation, demonstrating the existence of primary cilia and the ... More
Inhibition of 5-lipoxygenase-activating protein abrogates experimental liver injury: role of Kupffer cells.
AuthorsTitos E, Claria J, Planaguma A, Lopez-Parra M, Gonzalez-Periz A, Gaya J, Miquel R, Arroyo V, Rodes J
JournalJ Leukoc Biol
PubMed ID16033810
Activation of Kupffer cells is a prominent feature of necro-inflammatory liver injury. We have recently demonstrated that 5-lipoxygenase (5-LO) and its accessory protein, 5-LO-activating protein (FLAP), are essential for the survival of Kupffer cells in culture, as their inhibition drives these liver resident macrophages to programmed cell death. In the ... More
Effects of emulsified policosanols with different chain lengths on cholesterol metabolism in heterozygous LDL receptor-deficient mice.
AuthorsDullens SP, Mensink RP, Bragt MC, Kies AK, Plat J
JournalJ Lipid Res
PubMed ID18162663
Policosanol is a mixture of long-chain primary aliphatic saturated alcohols. Previous studies in humans and animals have shown that these compounds improved lipoprotein profiles. However, more-recent placebo-controlled studies could not confirm these promising effects. Octacosanol (C28), the main component of sugarcane-derived policosanol, is assumed to be the bioactive component. This ... More
Coexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed synovia.
AuthorsRuprecht CR, Gattorno M, Ferlito F, Gregorio A, Martini A, Lanzavecchia A, Sallusto F
JournalJ Exp Med
PubMed ID15939793
A better understanding of the role of CD4+CD25+ regulatory T cells in disease pathogenesis should follow from the discovery of reliable markers capable of discriminating regulatory from activated T cells. We report that the CD4+CD25+ population in synovial fluid of juvenile idiopathic arthritis (JIA) patients comprises both regulatory and effector ... More
Upstream stimulatory factor-2 regulates steroidogenic factor-1 expression in endometriosis.
AuthorsUtsunomiya H, Cheng YH, Lin Z, Reierstad S, Yin P, Attar E, Xue Q, Imir G, Thung S, Trukhacheva E, Suzuki T, Sasano H, Kim JJ, Yaegashi N, Bulun SE
JournalMol Endocrinol
PubMed ID18165439
Local estrogen biosynthesis is a major factor in the pathogenesis of endometriosis. Aberrant expression of steroidogenic acute regulatory protein (StAR) and aromatase in endometriotic tissue leads to an up-regulation of estrogen production. The transcription factor steroidogenic factor-1 (SF-1) activates the promoters of both StAR and aromatase in endometriotic tissue. We ... More
Direct maxacalcitol injection into hyperplastic parathyroids improves skeletal changes in secondary hyperparathyroidism.
AuthorsShiizaki K, Hatamura I, Negi S, Sakaguchi T, Saji F, Kunimoto K, Okamoto M, Imazeki I, Muragaki Y, Akizawa T
JournalKidney Int
PubMed ID16788697
Direct maxacalcitol (OCT) injection into a parathyroid gland (PTG) ameliorates several important etiologic factors of resistance to medical treatments for secondary hyperparathyroidism (s-HPT): the upregulations of vitamin D receptor (VDR) and Ca-sensing receptor (CaSR) in PTGs and the regression of PTG hyperplasia by the induction of apoptosis. In this study, ... More
Testing the importance of p27 degradation by the SCFskp2 pathway in murine models of lung and colon cancer.
AuthorsTimmerbeul I, Garrett-Engele CM, Kossatz U, Chen X, Firpo E, Grunwald V, Kamino K, Wilkens L, Lehmann U, Buer J, Geffers R, Kubicka S, Manns MP, Porter PL, Roberts JM, Malek NP
JournalProc Natl Acad Sci U S A
PubMed ID16966613
Decreased expression of the CDK inhibitor p27kip1 in human tumors directly correlates with increased resistance to chemotherapies, increased rates of metastasis, and an overall increased rate of patient mortality. It is thought that decreased p27 expression in tumors is caused by increased proteasomal turnover, in particular activation of the pathway ... More
Complex role of the mitochondrial targeting signal in the function of steroidogenic acute regulatory protein revealed by bacterial artificial chromosome transgenesis in vivo.
AuthorsSasaki G, Ishii T, Jeyasuria P, Jo Y, Bahat A, Orly J, Hasegawa T, Parker KL
JournalMol Endocrinol
PubMed ID18187601
The steroidogenic acute regulatory protein (StAR) stimulates the regulated production of steroid hormones in the adrenal cortex and gonads by facilitating the delivery of cholesterol to the inner mitochondrial membrane. To explore key aspects of StAR function within bona fide steroidogenic cells, we used a transgenic mouse model to explore ... More
NGF up-regulates TRPA1: implications for orofacial pain.
AuthorsDiogenes A, Akopian AN, Hargreaves KM
JournalJ Dent Res
PubMed ID17525356
The transient receptor potential ankyrin repeat 1 (TRPA1) channel is believed to be involved in many forms of acute and chronic hyperalgesia. Nerve Growth Factor (NGF) regulates chronic inflammatory hyperalgesia by controlling gene expression in sensory neurons, including genes involved in inflammatory hyperalgesia in the dental pulp. We hypothesized that ... More
Role for staphylococci in misguided thrombus resolution of chronic thromboembolic pulmonary hypertension.
AuthorsBonderman D, Jakowitsch J, Redwan B, Bergmeister H, Renner MK, Panzenbock H, Adlbrecht C, Georgopoulos A, Klepetko W, Kneussl M, Lang IM
JournalArterioscler Thromb Vasc Biol
PubMed ID18239156
OBJECTIVE: Acute pulmonary emboli usually resolve within 6 months. However, in 0.1% to 3.8% of cases thrombus transforms into fibrous masses. If vascular obstruction is severe, the resulting condition is chronic thromboembolic pulmonary hypertension (CTEPH). Patients who carry ventriculo-atrial (VA-) shunts for the treatment of hydrocephalus and report a history ... More
The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology.
AuthorsMeyer U, Nyffeler M, Engler A, Urwyler A, Schedlowski M, Knuesel I, Yee BK, Feldon J
JournalJ Neurosci
PubMed ID16672647
Disturbance to early brain development is implicated in several neuropsychiatric disorders including autism, schizophrenia, and mental retardation. Epidemiological studies have indicated that the risk of developing these disorders is enhanced by prenatal maternal infection, presumably as a result of neurodevelopmental defects triggered by cytokine-related inflammatory events. Here, we demonstrate that ... More
Transcription elongation factor S-II is required for definitive hematopoiesis.
AuthorsIto T, Arimitsu N, Takeuchi M, Kawamura N, Nagata M, Saso K, Akimitsu N, Hamamoto H, Natori S, Miyajima A, Sekimizu K
JournalMol Cell Biol
PubMed ID16581793
Transcription elongation factor S-II/TFIIS promotes readthrough of transcriptional blocks by stimulating nascent RNA cleavage activity of RNA polymerase II in vitro. The biologic significance of S-II function in higher eukaryotes, however, remains unclear. To determine its role in mammalian development, we generated S-II-deficient mice through targeted gene disruption. Homozygous null ... More
Erasure of cellular memory by fusion with pluripotent cells.
AuthorsDo JT, Han DW, Gentile L, Sobek-Klocke I, Stehling M, Lee HT, Scholer HR
JournalStem Cells
PubMed ID17218392
Pluripotent cells have been suggested as a prime source to reprogram somatic cells. We used F9 EC cells as a pluripotent partner to reprogram neurosphere cells (NSCs) because they exhibit a nonneural differentiation potential in the presence of retinoic acid. F9-NSC hybrid cells displayed various features of reprogramming, such as ... More
Neutrophil granulocytes uniquely express, among human blood cells, high levels of Methionine-sulfoxide-reductase enzymes.
AuthorsAchilli C, Ciana A, Rossi A, Balduini C, Minetti G
JournalJ Leukoc Biol
PubMed ID17938273
L-Methionine (Met), in its free form or when inserted in proteins, is sensitive to oxidation of its thioether group by reactive oxygen species from exogenous or endogenous sources. Two stable diastereomers of Met sulfoxide [Met-(O)] may be formed [Met-S-(O) and Met-R-(O)], but these can be reduced by two classes of ... More
Exendin-4 promotes liver cell proliferation and enhances the PDX-1-induced liver to pancreas transdifferentiation process.
AuthorsAviv V, Meivar-Levy I, Rachmut IH, Rubinek T, Mor E, Ferber S
JournalJ Biol Chem
PubMed ID19755420
Over the last few years, evidence has accumulated revealing the unexpected potential of committed mammalian cells to convert to a different phenotype via a process called transdifferentiation or adult cell reprogramming. These findings may have major practical implications because this process may facilitate the generation of functional autologous tissues that ... More
Endothelial CYP epoxygenase overexpression and soluble epoxide hydrolase disruption attenuate acute vascular inflammatory responses in mice.
Cytochrome P-450 (CYP)-derived epoxyeicosatrienoic acids (EETs) possess potent anti-inflammatory effects in vitro. However, the effect of increased CYP-mediated EET biosynthesis and decreased soluble epoxide hydrolase (sEH, Ephx2)-mediated EET hydrolysis on vascular inflammation in vivo has not been rigorously investigated. Consequently, we characterized acute vascular inflammatory responses to endotoxin in transgenic ... More
Effects of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 on cytokine production by human decidual cells.
The active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) is a potent immunomodulatory seco-steroid. We have demonstrated that several components of vitamin D metabolism and signaling are strongly expressed in human uterine decidua from first trimester pregnancies, suggesting that locally produced 1,25(OH)(2)D(3) may exert immunosuppressive effects during early stages of ... More
Expression of filtrin in human glomerular diseases.
AuthorsIhalmo P, Schmid H, Rastaldi MP, Mattinzoli D, Langham RG, Luimula P, Kilpikari R, Lassila M, Gilbert RE, Kerjaschki D, Kretzler M, Holthofer H
JournalNephrol Dial Transplant
PubMed ID17442742
BACKGROUND: Filtrin (NEPH3/KIRREL2) is a recently characterized member of the nephrin-like proteins of the immunoglobulin superfamily, and it has been suggested to participate in the maintenance of the glomerular filtration barrier in the kidney. In this study, the gene and protein expression of filtrin were examined in patients with acquired ... More
In vitro and in vivo enhanced generation of human A9 dopamine neurons from neural stem cells by Bcl-XL.
AuthorsCourtois ET, Castillo CG, Seiz EG, Ramos M, Bueno C, Liste I, Martinez-Serrano A
JournalJ Biol Chem
PubMed ID20106970
Human neural stem cells derived from the ventral mesencephalon (VM) are powerful research tools and candidates for cell therapies in Parkinson disease. Previous studies with VM dopaminergic neuron (DAn) precursors indicated poor growth potential and unstable phenotypical properties. Using the model cell line hVM1 (human ventral mesencephalic neural stem cell ... More
Effect of apolipoprotein E on the cerebral load of latent herpes simplex virus type 1 DNA.
AuthorsBurgos JS, Ramirez C, Sastre I, Valdivieso F
JournalJ Virol
PubMed ID16699018
Herpes simplex virus type 1 (HSV-1) is neurotropic and enters a latent state lasting the lifetime of the host. This pathogen has recently been proposed as a risk factor for Alzheimer's disease (AD) in conjunction with apolipoprotein E4 (ApoE4). In a murine acute infection model, we showed that viral neuroinvasiveness ... More
Haplotype analysis of CYP11A1 identifies promoter variants associated with breast cancer risk.
AuthorsYaspan BL, Breyer JP, Cai Q, Dai Q, Elmore JB, Amundson I, Bradley KM, Shu XO, Gao YT, Dupont WD, Zheng W, Smith JR
JournalCancer Res
PubMed ID17575134
The CYP11A1 gene encodes the cholesterol side chain cleavage enzyme that catalyzes the initial and rate-limiting step of steroidogenesis. A large number of epidemiologic studies have implicated the duration and degree of endogenous estrogen exposure in the development of breast cancer in women. Here, we conduct a systematic investigation of ... More
Mitochondrial uncoupling protein 2 mediates temperature heterogeneity in atherosclerotic plaques.
AuthorsVan De Parre TJ, Martinet W, Verheye S, Kockx MM, Van Langenhove G, Herman AG, De Meyer GR
JournalCardiovasc Res
PubMed ID18006489
AIMS: Rupture-prone atherosclerotic plaques show an elevated temperature, but a molecular explanation for this phenomenon is unknown. Here, we investigated whether mitochondrial uncoupling protein 2 (UCP2) could be involved because this protein is a macrophage homologue of thermogenin in brown fat tissue. METHODS AND RESULTS: Immunohistochemistry, western blotting, and real-time ... More
The Ras effectors NORE1A and RASSF1A are frequently inactivated in pheochromocytoma and abdominal paraganglioma.
AuthorsGeli J, Kiss N, Lanner F, Foukakis T, Natalishvili N, Larsson O, Kogner P, Hoog A, Clark GJ, Ekstrom TJ, Backdahl M, Farnebo F, Larsson C
JournalEndocr Relat Cancer
PubMed ID17395981
NORE1A (RASSF5) and RASSF1A are newly described Ras effectors with tumour suppressor functions. Both molecules are frequently inactivated in various cancers. In this study, we aimed to explore the potential involvement of NORE1A and RASSF1A in pheochromocytoma and abdominal paraganglioma tumorigenesis. A panel of 54 primary tumours was analysed for ... More
Specific blockade of VEGF and HER2 pathways results in greater growth inhibition of breast cancer xenografts that overexpress HER2.
AuthorsLe XF, Mao W, Lu C, Thornton A, Heymach JV, Sood AK, Bast RC Jr
JournalCell Cycle
PubMed ID19029832
We have previously reported that breast cancer cells which overexpress HER2 produce higher levels of VEGF than cells with low levels of HER2. This study tested the hypothesis that dual targeting of the VEGF (with VEGF-Trap) and HER2 (with trastuzumab) pathways would result in greater growth inhibition of HER2-overexpressing breast ... More
Hypoxia up-regulates expression of Eph receptors and ephrins in mouse skin.
AuthorsVihanto MM, Plock J, Erni D, Frey BM, Frey FJ, Huynh-Do U
JournalFaseb J
PubMed ID16081502
Eph receptor tyrosine kinases and their ligands (ephrins) are key players during the development of the embryonic vasculature; however, their role and regulation in adult angiogenesis remain to be defined. Both receptors and ligands have been shown to be up-regulated in a variety of tumors. To address the hypothesis that ... More
Phagocytosis of Borrelia burgdorferi, the Lyme disease spirochete, potentiates innate immune activation and induces apoptosis in human monocytes.
AuthorsCruz AR, Moore MW, La Vake CJ, Eggers CH, Salazar JC, Radolf JD
JournalInfect Immun
PubMed ID17938216
We have previously demonstrated that phagocytosed Borrelia burgdorferi induces activation programs in human peripheral blood mononuclear cells that differ qualitatively and quantitatively from those evoked by equivalent lipoprotein-rich lysates. Here we report that ingested B. burgdorferi induces significantly greater transcription of proinflammatory cytokine genes than do lysates and that live ... More
CD154 tone sets the signaling pathways and transcriptome generated in model CD40-pluricompetent L3055 Burkitt's lymphoma cells.
AuthorsStewart R, Wei W, Challa A, Armitage RJ, Arrand JR, Rowe M, Young LS, Eliopoulos A, Gordon J
JournalJ Immunol
PubMed ID17709483
Activated B cells reacting to small amounts of CD40L (CD154) maintain homeostasis by suppressing default apoptosis. Additional outcomes, particularly differentiation, demand higher CD40 occupancy. Here, focusing on survival, we compared changes in the transcriptome of pleiotropically competent, early passage L3055 Burkitt's lymphoma cells confronted with low (picomolar) and high (nanomolar) ... More
Patterns of gene expression that characterize long-term survival in advanced stage serous ovarian cancers.
AuthorsBerchuck A, Iversen ES, Lancaster JM, Pittman J, Luo J, Lee P, Murphy S, Dressman HK, Febbo PG, West M, Nevins JR, Marks JR
JournalClin Cancer Res
PubMed ID15897565
PURPOSE: A better understanding of the underlying biology of invasive serous ovarian cancer is critical for the development of early detection strategies and new therapeutics. The objective of this study was to define gene expression patterns associated with favorable survival. EXPERIMENTAL DESIGN: RNA from 65 serous ovarian cancers was analyzed ... More
Distinct expression of muscle-specific microRNAs (myomirs) in brown adipocytes.
AuthorsWalden TB, Timmons JA, Keller P, Nedergaard J, Cannon B
JournalJ Cell Physiol
PubMed ID18937285
MicroRNAs, a novel class of post-transcriptional gene regulators, have been demonstrated to be involved in several cellular processes regulating the expression of protein-coding genes. Here we examine murine white and brown primary cell cultures for differential expression of miRNAs. The adipogenesis-related miRNA miR-143 was highly expressed in mature white adipocytes ... More
Ligand specificity of the anaphylatoxin C5L2 receptor and its regulation on myeloid and epithelial cell lines.
AuthorsJohswich K, Martin M, Thalmann J, Rheinheimer C, Monk PN, Klos A
JournalJ Biol Chem
PubMed ID17068344
During complement activation the pro-inflammatory anaphylatoxins C3a and C5a are generated, which interact with the C3a receptor and C5a receptor (CD88), respectively. C5a and its degradation product C5a-des-Arg(74) also bind to the C5a receptor-like 2 (C5L2). C3a and C3a-des-Arg(77), also called acylation-stimulating protein, augment triglyceride synthesis and glucose uptake in ... More
Hyaluronan and CD44 antagonize mitogen-dependent cyclin D1 expression in mesenchymal cells.
AuthorsKothapalli D, Zhao L, Hawthorne EA, Cheng Y, Lee E, Pure E, Assoian RK
JournalJ Cell Biol
PubMed ID17296798
High molecular weight (HMW) hyaluronan (HA) is widely distributed in the extracellular matrix, but its biological activities remain incompletely understood. We previously reported that HMW-HA binding to CD44 antagonizes mitogen-induced S-phase entry in vascular smooth muscle cells (SMCs; Cuff, C.A., D. Kothapalli, I. Azonobi, S. Chun, Y. Zhang, R. Belkin, ... More
Post-transcriptional regulation of melanin biosynthetic enzymes by cAMP and resveratrol in human melanocytes.
AuthorsNewton RA, Cook AL, Roberts DW, Leonard JH, Sturm RA
JournalJ Invest Dermatol
PubMed ID17460731
Upregulation of microphthalmia-associated transcription factor (MITF) expression has been proposed to mediate melanogenesis stimulated by cAMP, whereas downregulation of MITF has been suggested to underlie the depigmentary effects of resveratrol, a promising chemotherapeutic found in red wine. We have assessed the contribution of MITF to pigmentation regulation by treating primary ... More
Differential expression of interferon (IFN) regulatory factors and IFN-stimulated genes at early times after West Nile virus infection of mouse embryo fibroblasts.
AuthorsScherbik SV, Stockman BM, Brinton MA
JournalJ Virol
PubMed ID17804507
Although lineage I West Nile virus (WNV) strain Eg101 induced beta interferon (IFN-beta) production as early as 12 h after infection in primary mouse embryo fibroblasts and did not inhibit the JAK-STAT signaling pathway, it was still able to replicate efficiently. To gain insights about possible viral countermeasures used by ... More
MCP-1/CCR2-dependent loop for fibrogenesis in human peripheral CD14-positive monocytes.
AuthorsSakai N, Wada T, Furuichi K, Shimizu K, Kokubo S, Hara A, Yamahana J, Okumura T, Matsushima K, Yokoyama H, Kaneko S
JournalJ Leukoc Biol
PubMed ID16415174
Monocyte/macrophage (Momicron) migration to sites of inflammation is a prerequisite cause of organ fibrosis. The recruitment and activation of Mo are regulated by C-C chemokines, especially monocyte chemoattractant protein-1 [(MCP-1)/CC chemokine ligand 2], which interacts with CC chemokine receptor 2 (CCR2). However, the mechanisms leading to fibrosis via MCP-1/CCR2 signaling ... More
The sphingosine 1-phosphate receptor agonist FTY720 differentially affects the sequestration of CD4+/CD25+ T-regulatory cells and enhances their functional activity.
AuthorsSawicka E, Dubois G, Jarai G, Edwards M, Thomas M, Nicholls A, Albert R, Newson C, Brinkmann V, Walker C
JournalJ Immunol
PubMed ID16339533
The sphingosine 1-phosphate (S1P) receptor agonist FTY720 is well known for its immunomodulatory activity, sequestering lymphocytes from blood and spleen into secondary lymphoid organs and thereby preventing their migration to sites of inflammation. Because inflammation is critically dependent on a balance between Ag-specific Th/effector cells and T-regulatory cells, we investigated ... More
The Thyroid Epidemiology, Audit, and Research Study (TEARS): The Natural History of Endogenous Subclinical Hyperthyroidism.
AuthorsVadiveloo T, Donnan PT, Cochrane L, Leese GP
JournalJ Clin Endocrinol Metab
PubMed ID20926532
Objective: For patients with subclinical hyperthyroidism (SH), the objective of the study was to define the rates of progression to frank hyperthyroidism and normal thyroid function. Design: Record-linkage technology was used retrospectively to identify patients with SH in the general population of Tayside, Scotland, from January 1, 1993, to December ... More
Cooperative interactions between RUNX2 and homeodomain protein-binding sites are critical for the osteoblast-specific expression of the bone sialoprotein gene.
AuthorsRoca H, Phimphilai M, Gopalakrishnan R, Xiao G, Franceschi RT
JournalJ Biol Chem
PubMed ID16000302
The bone sialoprotein (Bsp) gene provides an excellent model for studying mechanisms controlling osteoblast-specific gene expression. Although the RUNX2 transcription factor directly regulates many osteoblast-related genes, its function in Bsp expression remains uncertain. By using chromatin immunoprecipitation (ChIP) analysis in MC3T3-E1 (clone MC-4) preosteoblast cells, RUNX2 was shown to bind ... More
An analysis of select pathogenic messages in lesional and non-lesional psoriatic skin using non-invasive tape harvesting.
AuthorsBenson NR, Papenfuss J, Wong R, Motaal A, Tran V, Panko J, Krueger GG
JournalJ Invest Dermatol
PubMed ID16741508
We report the use of non-invasive tape stripping to sample psoriatic lesional and non-lesional skin in 96 patients. The procedure was well tolerated with any discomfort described as mild; we did not observe any cases of Koebner phenomena at any non-lesional tape-stripped sites. Tape-harvested epidermis was extracted for RNA, which ... More
Phosphorothioate-modified oligodeoxynucleotides inhibit human cytomegalovirus replication by blocking virus entry.
AuthorsLuganini A, Caposio P, Landolfo S, Gribaudo G
JournalAntimicrob Agents Chemother
PubMed ID18180342
Studies in animal models have provided evidence that Toll-like receptor 9 (TLR9) agonists, such as synthetic oligodeoxynucleotides (ODNs) that contain immunostimulatory deoxycytidyl-deoxyguanosine (CpG) motifs (CpG ODNs), protect against a wide range of viral pathogens. This antiviral activity has been suggested to be indirect and secondary to CpG-induced cytokines and inflammatory ... More
CDKN1C (p57KIP2) mRNA expression in human retinoblastomas.
AuthorsMadhavan J, Mallikarjuna K, Vikas K, George R, Bremner R, Kumaramanickavel G
JournalOphthalmic Genet
PubMed ID20565244
PURPOSE: Quantify cyclin dependent kinase inhibitor 1C (CDKN1C or p57KIP2) mRNA levels in human retinoblastoma tumors (RB) and associate with disease phenotype. METHODS: CDKN1C mRNA expression was quantified in 55 RB, 3 retinoblastoma cell lines, and 12 control retinas by real time PCR. Localization of CDKN1C protein was confirmed by ... More
Down-regulation of RNA editing in pediatric astrocytomas: ADAR2 editing activity inhibits cell migration and proliferation.
AuthorsCenci C, Barzotti R, Galeano F, Corbelli S, Rota R, Massimi L, Di Rocco C, O'Connell MA, Gallo A
JournalJ Biol Chem
PubMed ID18178553
Since alterations in post-transcriptional events can contribute to the appearance and/or progression of cancer, we investigated whether RNA editing, catalyzed by the ADAR (adenosine deaminases that act on RNA) enzymes, is altered in pediatric astrocytomas. We find a decrease in ADAR2 editing activity that seems to correlate with the grade ... More
Inhibition of proinflammatory genes in anti-GBM glomerulonephritis by targeted dexamethasone-loaded AbEsel liposomes.
AuthorsAsgeirsdottir SA, Zwiers PJ, Morselt HW, Moorlag HE, Bakker HI, Heeringa P, Kok JW, Kallenberg CG, Molema G, Kamps JA
JournalAm J Physiol Renal Physiol
PubMed ID18160627
E-selectin-directed targeted drug delivery was analyzed in anti-glomerular basement membrane glomerulonephritis. Liposomes conjugated with anti-E-selectin antibodies (Ab(Esel) liposomes) were internalized by activated endothelial cells in vitro through E-selectin-mediated endocytosis. At the onset of glomerulonephritis in mice, E-selectin was expressed on glomerular endothelial cells, which resulted in homing of Ab(Esel) liposomes ... More
Pulmonary immune responses to Propionibacterium acnes in C57BL/6 and BALB/c mice.
Propionibacterium acnes (PA) is a gram-positive anaerobic bacterium implicated as a putative etiologic agent of sarcoidosis. To characterize the pulmonary immune response to PA, C57BL/6 and BALB/c mice were intraperitoneally sensitized and intratracheally challenged with heat-killed bacteria. C57BL/6 mice challenged with PA developed a cellular immune response characterized by elevations ... More
Human plasmacytoid dendritic cells support Th17 cell effector function in response to TLR7 ligation.
AuthorsYu CF, Peng WM, Oldenburg J, Hoch J, Bieber T, Limmer A, Hartmann G, Barchet W, Eis-Hubinger AM, Novak N
JournalJ Immunol
PubMed ID20026744
Signals involved in the commitment of Th17 differentiation are of substantial interest for our understanding of antimicrobial defense mechanisms and autoimmune disorders. Various ways in which myeloid dendritic cells modulate Th17 differentiation have been identified. However, although plasmacytoid dendritic cells (PDCs) are regarded as important players in antiviral/antimicrobial host defense ... More
Coordinated multitissue transcriptional and plasma metabonomic profiles following acute caloric restriction in mice.
AuthorsSelman C, Kerrison ND, Cooray A, Piper MD, Lingard SJ, Barton RH, Schuster EF, Blanc E, Gems D, Nicholson JK, Thornton JM, Partridge L, Withers DJ
JournalPhysiol Genomics
PubMed ID16882887
Caloric restriction (CR) increases healthy life span in a range of organisms. The underlying mechanisms are not understood but appear to include changes in gene expression, protein function, and metabolism. Recent studies demonstrate that acute CR alters mortality rates within days in flies. Multitissue transcriptional changes and concomitant metabolic responses ... More
Hypoxia inducible factor-1 mediates effects of insulin on pancreatic cancer cells and disturbs host energy homeostasis.
Intratumoral hypoxia and paracrine insulin stimulate the expression of hypoxia inducible factor-1alpha (HIF-1alpha) in pancreatic cancer cells. In the present studies, we investigated whether insulin-induced HIF-1alpha expression is a prerequisite for insulin to induce other trophic effects in MiaPaCa2 human pancreatic cancer cells and whether inhibition of HIF-1alpha expression would ... More
p21 gene polymorphisms in systemic lupus erythematosus.
AuthorsKong EK, Chong WP, Wong WH, Lau CS, Chan TM, Ng PK, Song YQ, Mak W, Lau YL
JournalRheumatology (Oxford)
PubMed ID16837471
OBJECTIVE: Cyclin-dependent kinase inhibitor 1A (p21) is a negative regulator in the cell cycle. Development of sex-linked lupus-like syndrome in p21-/- mice and reduced p21 gene expression in patients with systemic lupus erythematosus (SLE) compared with those in healthy controls suggested that p21 is a susceptibility gene of SLE. We ... More
TRPV1 receptor signaling mediates afferent nerve sensitization during colitis-induced motility disorders in rats.
AuthorsDe Schepper HU, De Man JG, Ruyssers NE, Deiteren A, Van Nassauw L, Timmermans JP, Martinet W, Herman AG, Pelckmans PA, De Winter BY
JournalAm J Physiol Gastrointest Liver Physiol
PubMed ID17991707
Rats with experimental colitis suffer from impaired gastric emptying (GE). We previously showed that this phenomenon involves afferent neurons within the pelvic nerve. In this study, we aimed to identify the mediators involved in this afferent hyperactivation. Colitis was induced by trinitrobenzene sulfate (TNBS) instillation. We determined GE, distal front, ... More
Reduction of Pax9 gene dosage in an allelic series of mouse mutants causes hypodontia and oligodontia.
AuthorsKist R, Watson M, Wang X, Cairns P, Miles C, Reid DJ, Peters H
JournalHum Mol Genet
PubMed ID16236760
Missing teeth (hypodontia and oligodontia) are a common developmental abnormality in humans and heterozygous mutations of PAX9 have recently been shown to underlie a number of familial, non-syndromic cases. Whereas PAX9 haploinsufficiency has been suggested as the underlying genetic mechanism, it is not known how this affects tooth development. Here ... More
Reciprocal regulation of endothelial nitric-oxide synthase and NADPH oxidase by betulinic acid in human endothelial cells.
AuthorsSteinkamp-Fenske K, Bollinger L, Xu H, Yao Y, Horke S, Forstermann U, Li H
JournalJ Pharmacol Exp Ther
PubMed ID17496167
Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is a protective principle in the vasculature. Many cardiovascular diseases are associated with reduced NO bioactivity and eNOS uncoupling due to oxidative stress. Compounds that reverse eNOS uncoupling and increase eNOS expression are of therapeutic interest. Zizyphi Spinosi semen (ZSS) is ... More
Hypoxia increases macrophage motility, possibly by decreasing the heparan sulfate proteoglycan biosynthesis.
AuthorsAsplund A, Ostergren-Lunden G, Camejo G, Stillemark-Billton P, Bondjers G
JournalJ Leukoc Biol
PubMed ID19401393
Macrophages are recruited and retained in hypoxic sites in atherosclerotic lesions and tumors. Furthermore, macrophages are suggested to be a major source of HSPG synthesis in atherosclerotic lesions. HSPG are, among other things, known to regulate cell motility, cell adhesion, and receptor interaction. The aim of this study was to ... More
Flavopiridol targets c-KIT transcription and induces apoptosis in gastrointestinal stromal tumor cells.
Gastrointestinal stromal tumors (GIST) are characterized by activating mutations in the c-KIT gene which confers ligand-independent activation of the KIT receptor. Imatinib mesylate has been shown to effectively block constitutively active KIT and delay tumor growth. However, resistance to imatinib mesylate is emerging as a major clinical problem and novel ... More
Differential expression of cytokines in painful and painless neuropathies.
AuthorsUceyler N, Rogausch JP, Toyka KV, Sommer C
JournalNeurology
PubMed ID17606879
BACKGROUND: Pain is a common symptom in peripheral neuropathies. The factors determining why some peripheral neuropathies are painful and others are not are incompletely understood. Pro-inflammatory cytokines have been implicated to play a crucial role in the generation of pain. OBJECTIVE: To investigate whether cytokine profiles differ between patients with ... More
Preclinical pharmacokinetic and pharmacodynamic evaluation of metronomic and conventional temozolomide dosing regimens.
AuthorsZhou Q, Guo P, Wang X, Nuthalapati S, Gallo JM
JournalJ Pharmacol Exp Ther
PubMed ID17259446
Metronomic dosed (MD) chemotherapy as opposed to conventional dosed (CD) chemotherapy is considered an alternate strategy to target angiogenesis and limit host toxicity. Although this approach is promising, there has not been any attempt to define optimal metronomic dosing regimens by integrating pharmacokinetic (PK) with pharmacodynamic (PD) measurements. The aim ... More
Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers.
Proinflammatory cytokines inhibit learning and memory but the significance of interleukin-6 (IL-6) in acute cognitive deficits induced by the peripheral innate immune system is not known. To examine the functional role of IL-6 in hippocampus-mediated cognitive impairments associated with peripheral infections, C57BL6/J (IL-6(+/+)) and IL-6 knock-out (IL-6(-/-)) mice were trained ... More
Toxicogenomics of drug-induced hemolytic anemia by analyzing gene expression profiles in the spleen.
AuthorsRokushima M, Omi K, Imura K, Araki A, Furukawa N, Itoh F, Miyazaki M, Yamamoto J, Rokushima M, Okada M, Torii M, Kato I, Ishizaki J
JournalToxicol Sci
PubMed ID17698508
Hemolytic anemia is a serious adverse effect of therapeutic drugs that is caused by increased destruction of drug-damaged erythrocytes by macrophages in the spleen and liver. We previously applied a toxicogenomic approach to the toxicity by analyzing microarray data of the liver of rats dosed with two hemolytic agents: phenylhydrazine ... More
Differential ErbB1 signaling in squamous cell versus basal cell carcinoma of the skin.
AuthorsRittie L, Kansra S, Stoll SW, Li Y, Gudjonsson JE, Shao Y, Michael LE, Fisher GJ, Johnson TM, Elder JT
JournalAm J Pathol
PubMed ID17525275
In this study, we examined ErbB1 signaling in human basal and squamous cell carcinomas (BCC and SCC) of the skin in vivo. We used enzyme-linked immunosorbent assay, laser capture microdissection-coupled real-time reverse transcriptase-polymerase chain reaction, and immunohistochemistry to assess expression and activation levels of ErbB1 protein, ligands, and potential downstream ... More
RNASEN regulates cell proliferation and affects survival in esophageal cancer patients.
AuthorsSugito N, Ishiguro H, Kuwabara Y, Kimura M, Mitsui A, Kurehara H, Ando T, Mori R, Takashima N, Ogawa R, Fujii Y
JournalClin Cancer Res
PubMed ID17121874
PURPOSE: MicroRNAs (miRNA) are small noncoding RNAs thought to be involved in physiologic and developmental processes by negatively regulating the expression of target genes. Little is known about the role of miRNAs in normal and cancer cells. It is possible that deregulation of miRNA may contribute to the oncogenesis of ... More
Target genes of neuron-restrictive silencer factor are abnormally up-regulated in human myotilinopathy.
AuthorsBarrachina M, Moreno J, Juves S, Moreno D, Olive M, Ferrer I
JournalAm J Pathol
PubMed ID17823282
Myotilinopathy is a subgroup of myofibrillar myopathies caused by mutations in the myotilin gene in which there is aggregation of abnormal cytoskeletal proteins and ubiquitin. We report here on the accumulation of neuron-related proteins such as ubiquitin carboxy-terminal hydrolase L1 (UCHL1), synaptosomal-associated protein 25, synaptophysin, and alpha-internexin in aberrant protein ... More
ADP-ribosylation factor-like GTPase ARFRP1 is required for trans-Golgi to plasma membrane trafficking of E-cadherin.
AuthorsZahn C, Jaschke A, Weiske J, Hommel A, Hesse D, Augustin R, Lu L, Hong W, Florian S, Scheepers A, Joost HG, Huber O, Schurmann A
JournalJ Biol Chem
PubMed ID18662990
ADP-ribosylation factor-related protein 1 (ARFRP1) plays a specific role in Golgi function controlling recruitment of GRIP domain proteins and ARL1 to the trans-Golgi. Deletion of the mouse Arfrp1 gene causes embryonic lethality during early gastrulation, because epiblast cells detach from the ectodermal cell layer and do not differentiate to mesodermal ... More
Innate immune responses to TREM-1 activation: overlap, divergence, and positive and negative cross-talk with bacterial lipopolysaccharide.
AuthorsDower K, Ellis DK, Saraf K, Jelinsky SA, Lin LL
JournalJ Immunol
PubMed ID18292579
TREM-1 (triggering receptor expressed on myeloid cells-1) is an orphan immunoreceptor expressed on monocytes, macrophages, and neutrophils. TREM-1 associates with and signals via the adapter protein DAP12/TYROBP, which contains an ITAM. TREM-1 activation by receptor cross-linking has been shown to be proinflammatory and to amplify some cellular responses to TLR ... More
Epigenetic aberration of the human REELIN gene in psychiatric disorders.
AuthorsTamura Y, Kunugi H, Ohashi J, Hohjoh H
JournalMol Psychiatry
PubMed ID17310238
Epigenetic genome modifications such as DNA methylation appear to be involved in various diseases. Here, we suggest that the levels of DNA methylation at the BssHII methylation-sensitive restriction enzyme sites in the human REELIN (RELN) gene in the forebrain vary among individuals. Interestingly, although a statistically significant correlation between the ... More
Cardiac concentric remodelling induced by non-aromatizable (dihydro-)testosterone is antagonized by oestradiol in ovariectomized rats.
AuthorsTivesten A, Bollano E, Nystrom HC, Alexanderson C, Bergstrom G, Holmang A
JournalJ Endocrinol
PubMed ID16731780
Previous studies on the cardiovascular effects of androgens in females, most of them using testosterone treatment, have yielded conflicting results. Testosterone is metabolized into oestradiol (E2) and dihydrotestosterone (DHT) within cardiovascular tissues. The aim of the present study was to explore the cardiovascular effects exerted by E2 and the non-aromatizable ... More
Glomerulus-specific mRNA transcripts and proteins identified through kidney expressed sequence tag database analysis.
AuthorsHe L, Sun Y, Patrakka J, Mostad P, Norlin J, Xiao Z, Andrae J, Tryggvason K, Samuelsson T, Betsholtz C, Takemoto M
JournalKidney Int
PubMed ID17332733
The kidney glomerulus plays a crucial role in blood filtration but the molecular composition and physiology of the glomerulus is not well understood. We previously constructed and large-scale sequenced four mouse glomerular expressed sequence tag (EST) libraries from newborn and adult mouse glomeruli. Here, we compared glomerular EST profiles with ... More
Distinct roles for IFN regulatory factor (IRF)-3 and IRF-7 in the activation of antitumor properties of human macrophages.
AuthorsRomieu-Mourez R, Solis M, Nardin A, Goubau D, Baron-Bodo V, Lin R, Massie B, Salcedo M, Hiscott J
JournalCancer Res
PubMed ID17079482
When properly activated, macrophages can be tumoricidal, thus making them attractive additions to standard cancer therapies. To this end, tolerance and activity of human autologous IFN-gamma-activated macrophages, produced in large scale for clinical use (MAK cells), have been assessed in pilot trials in cancer patients. In the present study, we ... More
HB-EGF/HER-1 signaling in bone marrow mesenchymal stem cells: inducing cell expansion and reversibly preventing multilineage differentiation.
AuthorsKrampera M, Pasini A, Rigo A, Scupoli MT, Tecchio C, Malpeli G, Scarpa A, Dazzi F, Pizzolo G, Vinante F
JournalBlood
PubMed ID15755902
Epidermal growth factor receptor-1 (EGFR-1/HER-1/ErbB-1) regulates proliferation and cell fate during epidermal development. HER-1 is activated by several EGF-family ligands including heparin-binding epidermal growth factor-like growth factor (HB-EGF), a mitogenic and chemotactic molecule that participates in tissue repair, tumor growth, and other tissue-modeling phenomena, such as angiogenesis and fibrogenesis. We ... More
Nuclear pregnane X receptor cross-talk with FoxA2 to mediate drug-induced regulation of lipid metabolism in fasting mouse liver.
AuthorsNakamura K, Moore R, Negishi M, Sueyoshi T
JournalJ Biol Chem
PubMed ID17267396
Upon drug activation, the nuclear pregnane X receptor (PXR) regulates not only hepatic drug but also energy metabolism. Using Pxr(-/-) mice, we have now investigated the PXR-mediated repression of lipid metabolism in the fasting livers. Treatment with PXR activator pregnenolone 16alpha-carbonitrile (PCN) down-regulated the mRNA levels of carnitine palmitoyltransferase 1A ... More
Mitogen-activated protein kinase kinase inhibition enhances nuclear proapoptotic function of p53 in acute myelogenous leukemia cells.
AuthorsKojima K, Konopleva M, Samudio IJ, Ruvolo V, Andreeff M
JournalCancer Res
PubMed ID17409429
Activation of the Raf/MEK/ERK pathway and inactivation of wild-type p53 by Mdm2 overexpression are frequent molecular events in acute myelogenous leukemia (AML). We investigated the interaction of Raf/MEK/ERK and p53 pathways after their simultaneous blockades using a selective small-molecule antagonist of Mdm2, Nutlin-3a, and a pharmacologic MEK-specific inhibitor, PD98059. We ... More
Impact of angiogenesis inhibition by sunitinib on tumor distribution of temozolomide.
AuthorsZhou Q, Guo P, Gallo JM
JournalClin Cancer Res
PubMed ID18316579
PURPOSE: As combination chemotherapy of antiangiogenic agents with conventional chemotherapeutic drugs continues to evolve, an understanding of the pharmacokinetic and pharmacodynamic variables associated with optimal treatment is needed. Thus, the effect of the multitargeted tyrosine kinase inhibitor sunitinib on tumor distribution of temozolomide was investigated to evaluate conditions for optimal ... More
Tumor immunobiological differences in prostate cancer between African-American and European-American men.
AuthorsWallace TA, Prueitt RL, Yi M, Howe TM, Gillespie JW, Yfantis HG, Stephens RM, Caporaso NE, Loffredo CA, Ambs S
JournalCancer Res
PubMed ID18245496
The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared with European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American ... More
Gene expression profiles in murine hematopoietic stem cells revisited: analysis of cDNA libraries reveals high levels of translational and metabolic activities.
AuthorsHuttmann A, Duhrsen U, Heydarian K, Klein-Hitpass L, Boes T, Boyd AW, Li CL
JournalStem Cells
PubMed ID16574753
Gene expression studies from hematopoietic stem cell (HSC) populations purified to variable degrees have defined a set of stemness genes. Unexpectedly, results also hinted toward a HSC chromatin poised in a wide-open state. With the aim of providing a robust tool for further studies into the molecular biology of HSCs, ... More
Secreted frizzled-related protein 1 loss contributes to tumor phenotype of clear cell renal cell carcinoma.
AuthorsGumz ML, Zou H, Kreinest PA, Childs AC, Belmonte LS, LeGrand SN, Wu KJ, Luxon BA, Sinha M, Parker AS, Sun LZ, Ahlquist DA, Wood CG, Copland JA
JournalClin Cancer Res
PubMed ID17699851
PURPOSE: Incidence and mortality rates for renal cell carcinoma (RCC) have been rising for decades. Unfortunately, the molecular events that support RCC carcinogenesis remain poorly understood. In an effort to gain a better understanding of signaling events in clear cell RCC (cRCC), we investigated the antitumor activity of secreted frizzled-related ... More
An apolipoprotein E-mimetic stimulates axonal regeneration and remyelination after peripheral nerve injury.
AuthorsLi FQ, Fowler KA, Neil JE, Colton CA, Vitek MP
JournalJ Pharmacol Exp Ther
PubMed ID20406857
Elevated apolipoprotein E (apoE) synthesis within crushed sciatic nerves advocates that apoE could benefit axonal repair and reconstruction of axonal and myelin membranes. We created an apoE-mimetic peptide, COG112 (acetyl-RQIKIWFQNRRMKWKKCLRVRLASHLRKLRKRLL-amide), and found that postinjury treatment with COG112 significantly improved recovery of motor and sensory function following sciatic nerve crush in ... More
eIF4E activation is commonly elevated in advanced human prostate cancers and significantly related to reduced patient survival.
AuthorsGraff JR, Konicek BW, Lynch RL, Dumstorf CA, Dowless MS, McNulty AM, Parsons SH, Brail LH, Colligan BM, Koop JW, Hurst BM, Deddens JA, Neubauer BL, Stancato LF, Carter HW, Douglass LE, Carter JH
JournalCancer Res
PubMed ID19383915
Elevated eukaryotic translation initiation factor 4E (eIF4E) function induces malignancy in experimental models by selectively enhancing translation of key malignancy-related mRNAs (c-myc and BCL-2). eIF4E activation may reflect increased eIF4E expression or phosphorylation of its inhibitory binding proteins (4E-BP). By immunohistochemical analyses of 148 tissues from 89 prostate cancer patients, ... More
Role of NADPH oxidase and iNOS in vasoconstrictor responses of vessels from hypertensive and normotensive rats.
AuthorsAlvarez Y, Briones AM, Hernanz R, Perez-Giron JV, Alonso MJ, Salaices M
JournalBr J Pharmacol
PubMed ID17994107
BACKGROUND AND PURPOSE: To analyse the influence of hypertension in the modulation induced by inducible NOS (iNOS)-derived NO and superoxide anion (O(2) (*-)) of vasoconstrictor responses and the sources of O(2) (*-) implicated. EXPERIMENTAL APPROACH: Vascular reactivity experiments were performed in segments of aorta from normotensive, Wistar Kyoto (WKY) and ... More