Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition.

abstract：:Retinal neovascularization is a major cause of blindness in such disorders as retinopathy of prematurity, proliferative diabetic retinopathy and senile macular degeneration. Because ligation of vitronectin receptor-type integrins appears to be required for the survival and maturation of newly formed but not quiescent ...

journal_title：Nature medicine

authors： Hammes HP,Brownlee M,Jonczyk A,Sutter A,Preissner KT

更新日期：1996-05-01 00:00:00

abstract：:Migration inhibitory factor (MIF) is known to exert significant pro-inflammatory effects and has the potential to override the anti-inflammatory action of glucocorticoids. In this study we have identified significant quantities of MIF in the alveolar airspaces of patients with acute respiratory distress syndrome (ARDS...

journal_title：Nature medicine

authors： Donnelly SC,Haslett C,Reid PT,Grant IS,Wallace WA,Metz CN,Bruce LJ,Bucala R

更新日期：1997-03-01 00:00:00

abstract：:Hemophilia B is a severe X-linked bleeding diathesis caused by the absence of functional blood coagulation factor IX, and is an excellent candidate for treatment of a genetic disease by gene therapy. Using an adeno-associated viral vector, we demonstrate sustained expression (>17 months) of factor IX in a large-animal...

journal_title：Nature medicine

authors： Herzog RW,Yang EY,Couto LB,Hagstrom JN,Elwell D,Fields PA,Burton M,Bellinger DA,Read MS,Brinkhous KM,Podsakoff GM,Nichols TC,Kurtzman GJ,High KA

更新日期：1999-01-01 00:00:00

abstract：:Molecular targeted therapy has the potential to dramatically improve survival in patients with cancer. However, complete and durable responses to targeted therapy are rare in individuals with advanced-stage solid cancers. Even the most effective targeted therapies generally do not induce a complete tumor response, res...

journal_title：Nature medicine

authors： Bivona TG,Doebele RC

更新日期：2016-05-05 00:00:00

abstract：:Oxygen-regulated protein 150 kD (ORP150) is a novel endoplasmic-reticulum-associated chaperone induced by hypoxia/ischemia. Although ORP150 was sparingly upregulated in neurons from human brain undergoing ischemic stress, there was robust induction in astrocytes. Cultured neurons overexpressing ORP150 were resistant t...

journal_title：Nature medicine

authors： Tamatani M,Matsuyama T,Yamaguchi A,Mitsuda N,Tsukamoto Y,Taniguchi M,Che YH,Ozawa K,Hori O,Nishimura H,Yamashita A,Okabe M,Yanagi H,Stern DM,Ogawa S,Tohyama M

更新日期：2001-03-01 00:00:00

abstract：:Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. These parasites replicate intracellularly in macrophages, and the primary mechanisms underlying host resistance involve the production of nitric oxide (NO). In this study...

journal_title：Nature medicine

authors： Lima-Junior DS,Costa DL,Carregaro V,Cunha LD,Silva AL,Mineo TW,Gutierrez FR,Bellio M,Bortoluci KR,Flavell RA,Bozza MT,Silva JS,Zamboni DS

更新日期：2013-07-01 00:00:00

abstract：:Members of the suppressor of cytokine signaling (SOCS) family are involved in the pathogenesis of many inflammatory diseases. SOCS-3 is predominantly expressed in T-helper type 2 (T(H)2) cells, but its role in T(H)2-related allergic diseases remains to be investigated. In this study we provide a strong correlation bet...

journal_title：Nature medicine

authors： Seki Y,Inoue H,Nagata N,Hayashi K,Fukuyama S,Matsumoto K,Komine O,Hamano S,Himeno K,Inagaki-Ohara K,Cacalano N,O'Garra A,Oshida T,Saito H,Johnston JA,Yoshimura A,Kubo M

更新日期：2003-08-01 00:00:00

abstract：:A high-fat diet increases the risk of colon, breast and prostate cancer. The molecular mechanism by which dietary lipids promote tumorigenesis is unknown. Their effects may be mediated at least in part by the peroxisome proliferator-activated receptors (PPARs). These ligand-activated nuclear receptors modulate gene ex...

journal_title：Nature medicine

authors： Saez E,Tontonoz P,Nelson MC,Alvarez JG,Ming UT,Baird SM,Thomazy VA,Evans RM

更新日期：1998-09-01 00:00:00

abstract：:Copy number variants are a recently discovered source of large-scale genomic diversity present in all individuals. We capitalize on these inherent genomic differences, focusing on deletion polymorphisms, to develop informative fluorescence in situ hybridization probes with the ability to unequivocally distinguish betw...

journal_title：Nature medicine

authors： Wu D,Vu Q,Nguyen A,Stone JR,Stubbs H,Kuhlmann G,Sholl LM,Iafrate AJ

更新日期：2009-02-01 00:00:00

abstract：:The human CD4 molecule (hCD4) is expressed on T lymphocytes and macrophages and acts as a key component of the cellular receptor for HIV. At baseline, hCD4 transgenic mice expressed hCD4 on microglia, the resident mononuclear phagocytes of the brain, and showed no neuronal damage. Activation of brain microglia by peri...

journal_title：Nature medicine

authors： Buttini M,Westland CE,Masliah E,Yafeh AM,Wyss-Coray T,Mucke L

更新日期：1998-04-01 00:00:00

abstract：:Deep brain stimulation (DBS) is a widely used neurosurgical approach to treating tremor and other movement disorders. In addition, the use of DBS in a number of psychiatric diseases, including obsessive-compulsive disorders and depression, is currently being tested. Despite the rapid increase in the number of individu...

journal_title：Nature medicine

authors： Bekar L,Libionka W,Tian GF,Xu Q,Torres A,Wang X,Lovatt D,Williams E,Takano T,Schnermann J,Bakos R,Nedergaard M

更新日期：2008-01-01 00:00:00

abstract：:Natalizumab (NZM), a humanized monoclonal IgG4 antibody to α4 integrins, is used to treat patients with relapsing-remitting multiple sclerosis (MS)1,2, but in about 6% of the cases persistent neutralizing anti-drug antibodies (ADAs) are induced leading to therapy discontinuation3,4. To understand the basis of the ADA ...

journal_title：Nature medicine

authors： Cassotta A,Mikol V,Bertrand T,Pouzieux S,Le Parc J,Ferrari P,Dumas J,Auer M,Deisenhammer F,Gastaldi M,Franciotta D,Silacci-Fregni C,Fernandez Rodriguez B,Giacchetto-Sasselli I,Foglierini M,Jarrossay D,Geiger R,Sallusto

更新日期：2019-09-01 00:00:00

abstract：:Using in vitro drug sensitivity data coupled with Affymetrix microarray data, we developed gene expression signatures that predict sensitivity to individual chemotherapeutic drugs. Each signature was validated with response data from an independent set of cell line studies. We further show that many of these signature...

journal_title：Nature medicine

authors： Potti A,Dressman HK,Bild A,Riedel RF,Chan G,Sayer R,Cragun J,Cottrill H,Kelley MJ,Petersen R,Harpole D,Marks J,Berchuck A,Ginsburg GS,Febbo P,Lancaster J,Nevins JR

更新日期：2006-11-01 00:00:00

abstract：:The use of genetically manipulated mouse models, gene and protein discovery and the cataloguing of genetic mutations have each allowed us to obtain new insights into skeletal morphogenesis and remodeling. These techniques have made it possible to identify molecules that are obligatory for specific cellular functions, ...

journal_title：Nature medicine

authors： Zaidi M

更新日期：2007-07-01 00:00:00

abstract：:Recent studies suggest that statins can function to protect the vasculature in a manner that is independent of their lipid-lowering activity. We show here that statins rapidly activate the protein kinase Akt/PKB in endothelial cells. Accordingly, simvastatin enhanced phosphorylation of the endogenous Akt substrate end...

journal_title：Nature medicine

authors： Kureishi Y,Luo Z,Shiojima I,Bialik A,Fulton D,Lefer DJ,Sessa WC,Walsh K

更新日期：2000-09-01 00:00:00

abstract：:Preventing the immune escape of tumor cells by blocking inhibitory checkpoints, such as the interaction between programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) receptor, is a powerful anticancer approach. However, many patients do not respond to checkpoint blockade. Tumor PD-L1 expression is a potentia...

journal_title：Nature medicine

authors： Cerezo M,Guemiri R,Druillennec S,Girault I,Malka-Mahieu H,Shen S,Allard D,Martineau S,Welsch C,Agoussi S,Estrada C,Adam J,Libenciuc C,Routier E,Roy S,Désaubry L,Eggermont AM,Sonenberg N,Scoazec JY,Eychène A,Vagner

更新日期：2018-12-01 00:00:00

abstract：:Both the risk and the rate of development of atherosclerosis are increased in diabetics, but the mechanisms involved are unknown. Here we report a glucose-mediated increase in CD36 mRNA translation efficiency that results in increased expression of the macrophage scavenger receptor CD36. Expression of CD36 was increas...

journal_title：Nature medicine

authors： Griffin E,Re A,Hamel N,Fu C,Bush H,McCaffrey T,Asch AS

更新日期：2001-07-01 00:00:00

abstract：:Efforts to identify and annotate cancer driver genetic lesions have been focused primarily on the analysis of protein-coding genes; however, most genetic abnormalities found in human cancer are located in intergenic regions. Here we identify a new long range-acting MYC enhancer controlled by NOTCH1 that is targeted by...

journal_title：Nature medicine

authors： Herranz D,Ambesi-Impiombato A,Palomero T,Schnell SA,Belver L,Wendorff AA,Xu L,Castillo-Martin M,Llobet-Navás D,Cordon-Cardo C,Clappier E,Soulier J,Ferrando AA

更新日期：2014-10-01 00:00:00

abstract：:The major known genetic risk factors in multiple sclerosis reside in the major histocompatibility complex (MHC) region. Although there is strong evidence implicating MHC class II alleles and CD4(+) T cells in multiple sclerosis pathogenesis, possible contributions from MHC class I genes and CD8(+) T cells are controve...

journal_title：Nature medicine

authors： Friese MA,Jakobsen KB,Friis L,Etzensperger R,Craner MJ,McMahon RM,Jensen LT,Huygelen V,Jones EY,Bell JI,Fugger L

更新日期：2008-11-01 00:00:00

abstract：:Despite the central role of the liver in the regulation of glucose and lipid metabolism, there are currently no methods to directly assess hepatic oxidative metabolism in humans in vivo. By using a new (13)C-labeling strategy in combination with (13)C magnetic resonance spectroscopy, we show that rates of mitochondria...

journal_title：Nature medicine

authors： Befroy DE,Perry RJ,Jain N,Dufour S,Cline GW,Trimmer JK,Brosnan J,Rothman DL,Petersen KF,Shulman GI

更新日期：2014-01-01 00:00:00

abstract：:Mice carrying mutations in both the dystrophin and utrophin genes die prematurely as a consequence of severe muscular dystrophy. Here, we show that intravascular administration of recombinant adeno-associated viral (rAAV) vectors carrying a microdystrophin gene restores expression of dystrophin in the respiratory, car...

journal_title：Nature medicine

authors： Gregorevic P,Allen JM,Minami E,Blankinship MJ,Haraguchi M,Meuse L,Finn E,Adams ME,Froehner SC,Murry CE,Chamberlain JS

更新日期：2006-07-01 00:00:00

abstract：:A variable region gene of the T-cell receptor, V beta 8.2, is rearranged, and its product is expressed on pathogenic T cells that induce experimental autoimmune encephalomyelitis (EAE) in H-2u mice after immunization with myelin basic protein (MBP). Vaccination of these mice with naked DNA encoding V beta 8.2 protecte...

journal_title：Nature medicine

authors： Waisman A,Ruiz PJ,Hirschberg DL,Gelman A,Oksenberg JR,Brocke S,Mor F,Cohen IR,Steinman L

更新日期：1996-08-01 00:00:00

abstract：:Spinal bulbar muscular atrophy (SBMA) is a motor neuron disease caused by toxic gain of function of the androgen receptor (AR). Previously, we found that co-regulator binding through the activation function-2 (AF2) domain of AR is essential for pathogenesis, suggesting that AF2 may be a potential drug target for selec...

journal_title：Nature medicine

authors： Badders NM,Korff A,Miranda HC,Vuppala PK,Smith RB,Winborn BJ,Quemin ER,Sopher BL,Dearman J,Messing J,Kim NC,Moore J,Freibaum BD,Kanagaraj AP,Fan B,Tillman H,Chen PC,Wang Y,Freeman BB III,Li Y,Kim HJ,La Spada AR

更新日期：2018-05-01 00:00:00

abstract：:Conceptual and practical advances in molecular medicine are changing our understanding of cancer pathogenesis. In time this should provide the opportunity to alter the natural history of many cancers. ...

journal_title：Nature medicine

authors： Karp JE,Broder S

更新日期：1995-04-01 00:00:00

abstract：:Physical function declines in old age, portending disability, increased health expenditures, and mortality. Cellular senescence, leading to tissue dysfunction, may contribute to these consequences of aging, but whether senescence can directly drive age-related pathology and be therapeutically targeted is still unclear...

journal_title：Nature medicine

authors： Xu M,Pirtskhalava T,Farr JN,Weigand BM,Palmer AK,Weivoda MM,Inman CL,Ogrodnik MB,Hachfeld CM,Fraser DG,Onken JL,Johnson KO,Verzosa GC,Langhi LGP,Weigl M,Giorgadze N,LeBrasseur NK,Miller JD,Jurk D,Singh RJ,Allison

更新日期：2018-08-01 00:00:00

abstract：:Here we show that ischemia induces sustained contraction of pericytes on microvessels in the intact mouse brain. Pericytes remain contracted despite successful reopening of the middle cerebral artery after 2 h of ischemia. Pericyte contraction causes capillary constriction and obstructs erythrocyte flow. Suppression o...

journal_title：Nature medicine

authors： Yemisci M,Gursoy-Ozdemir Y,Vural A,Can A,Topalkara K,Dalkara T

更新日期：2009-09-01 00:00:00

abstract：:Genetic alterations in malignant tissues are potential targets for gene-based cancer therapies. Alternatively, aberrant expression of certain specific genes associated with malignant transformation may be envisioned to enhance the expression of chemosensitizing drugs. Epstein-Barr virus (EBV)-related B-cell lymphomas ...

journal_title：Nature medicine

authors： Franken M,Estabrooks A,Cavacini L,Sherburne B,Wang F,Scadden DT

更新日期：1996-12-01 00:00:00

abstract：:Idiopathic voiding disorders affect up to 10-15% of men and women. We describe bladder abnormalities in mice with targeted deletion of the gene for neuronal nitric oxide synthase which model the clinical disorders. The mice possess hypertrophic dilated bladders and dysfunctional urinary outlets which do not relax in r...

journal_title：Nature medicine

authors： Burnett AL,Calvin DC,Chamness SL,Liu JX,Nelson RJ,Klein SL,Dawson VL,Dawson TM,Snyder SH

更新日期：1997-05-01 00:00:00

abstract：:Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are key regulators of the apoptotic process. This family comprises proapoptotic and prosurvival proteins, and shifting the balance toward the latter is an established mechanism whereby cancer cells evade apoptosis. The therapeutic potential of directly inhibiting pr...

journal_title：Nature medicine

authors： Souers AJ,Leverson JD,Boghaert ER,Ackler SL,Catron ND,Chen J,Dayton BD,Ding H,Enschede SH,Fairbrother WJ,Huang DC,Hymowitz SG,Jin S,Khaw SL,Kovar PJ,Lam LT,Lee J,Maecker HL,Marsh KC,Mason KD,Mitten MJ,Nimmer PM

更新日期：2013-02-01 00:00:00

abstract：:Pulmonary hypertension (PH) is characterized by increased proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs). Forkhead box O (FoxO) transcription factors are key regulators of cellular proliferation. Here we show that in pulmonary vessels and PASMCs of human and experimental PH lun...

journal_title：Nature medicine

authors： Savai R,Al-Tamari HM,Sedding D,Kojonazarov B,Muecke C,Teske R,Capecchi MR,Weissmann N,Grimminger F,Seeger W,Schermuly RT,Pullamsetti SS

更新日期：2014-11-01 00:00:00