Leukocytes mediate retinal vascular remodeling during development and vaso-obliteration in disease.

abstract：:Phase 3 trials are the mainstay of drug development across medicine but have often not met expectations set by preceding phase 2 studies. A systematic meta-analysis evaluated all randomized controlled, double-blind trials investigating targeted disease-modifying anti-rheumatic drugs in rheumatoid and psoriatic arthrit...

journal_title：Nature medicine

authors： Kerschbaumer A,Smolen JS,Herkner H,Stefanova T,Chwala E,Aletaha D

更新日期：2020-06-01 00:00:00

abstract：:In the nervous system, NMDA receptors (NMDARs) participate in neurotransmission and modulate the viability of neurons. In contrast, little is known about the role of NMDARs in pancreatic islets and the insulin-secreting beta cells whose functional impairment contributes to diabetes mellitus. Here we found that inhibit...

journal_title：Nature medicine

authors： Marquard J,Otter S,Welters A,Stirban A,Fischer A,Eglinger J,Herebian D,Kletke O,Klemen MS,Stožer A,Wnendt S,Piemonti L,Köhler M,Ferrer J,Thorens B,Schliess F,Rupnik MS,Heise T,Berggren PO,Klöcker N,Meissner T,Ma

更新日期：2015-04-01 00:00:00

abstract：:Cells from the telomerase knockout mouse immortalize with an approximately ten million-fold greater frequency than human cells. In this commentary, Wright and Shay discuss the implications of this difference between mice and men and its relationship to cancer. ...

journal_title：Nature medicine

authors： Wright WE,Shay JW

更新日期：2000-08-01 00:00:00

abstract：:Although programmed death-ligand 1-programmed death 1 (PD-L1-PD-1) inhibitors are broadly efficacious, improved outcomes have been observed in patients with high PD-L1 expression or high tumor mutational burden (TMB). PD-L1 testing is required for checkpoint inhibitor monotherapy in front-line non-small-cell lung canc...

journal_title：Nature medicine

authors： Gandara DR,Paul SM,Kowanetz M,Schleifman E,Zou W,Li Y,Rittmeyer A,Fehrenbacher L,Otto G,Malboeuf C,Lieber DS,Lipson D,Silterra J,Amler L,Riehl T,Cummings CA,Hegde PS,Sandler A,Ballinger M,Fabrizio D,Mok T,Shames

更新日期：2018-09-01 00:00:00

abstract：:Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interaction...

journal_title：Nature medicine

authors： Said EA,Dupuy FP,Trautmann L,Zhang Y,Shi Y,El-Far M,Hill BJ,Noto A,Ancuta P,Peretz Y,Fonseca SG,Van Grevenynghe J,Boulassel MR,Bruneau J,Shoukry NH,Routy JP,Douek DC,Haddad EK,Sekaly RP

更新日期：2010-04-01 00:00:00

abstract：:The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes under...

journal_title：Nature medicine

authors： Bilkei-Gorzo A,Albayram O,Draffehn A,Michel K,Piyanova A,Oppenheimer H,Dvir-Ginzberg M,Rácz I,Ulas T,Imbeault S,Bab I,Schultze JL,Zimmer A

更新日期：2017-06-01 00:00:00

abstract：:Immunodeficiency is a barrier to successful vaccination in individuals with cancer and chronic infection. We performed a randomized phase 1/2 study in lymphopenic individuals after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for myeloma. Combination immunotherapy consisting of a singl...

journal_title：Nature medicine

authors： Rapoport AP,Stadtmauer EA,Aqui N,Badros A,Cotte J,Chrisley L,Veloso E,Zheng Z,Westphal S,Mair R,Chi N,Ratterree B,Pochran MF,Natt S,Hinkle J,Sickles C,Sohal A,Ruehle K,Lynch C,Zhang L,Porter DL,Luger S,Guo C,

更新日期：2005-11-01 00:00:00

abstract：:We have previously shown that a single portal vein infusion of a recombinant adeno-associated viral vector (rAAV) expressing canine Factor IX (F.IX) resulted in long-term expression of therapeutic levels of F.IX in dogs with severe hemophilia B. We carried out a phase 1/2 dose-escalation clinical study to extend this ...

journal_title：Nature medicine

authors： Manno CS,Pierce GF,Arruda VR,Glader B,Ragni M,Rasko JJ,Ozelo MC,Hoots K,Blatt P,Konkle B,Dake M,Kaye R,Razavi M,Zajko A,Zehnder J,Rustagi PK,Nakai H,Chew A,Leonard D,Wright JF,Lessard RR,Sommer JM,Tigges M,S

更新日期：2006-03-01 00:00:00

abstract：:Modest clinical outcomes of dendritic-cell (DC) vaccine trials call for the refinement of DC vaccine design. Although many potential antigens have been identified, development of methods to enhance antigen presentation by DCs has lagged. We have engineered a potent, drug-inducible CD40 (iCD40) receptor that permits te...

journal_title：Nature medicine

authors： Hanks BA,Jiang J,Singh RA,Song W,Barry M,Huls MH,Slawin KM,Spencer DM

更新日期：2005-02-01 00:00:00

abstract：:In the version of this article originally published, Dimitry G. Sayenko's affiliations were not correct. The following affiliation for this author was missing: Department of Neurosurgery, Center for Neuroregeneration, Houston Methodist Research Institute, Houston, TX, USA. This affiliation has been added for the autho...

journal_title：Nature medicine

authors： Gill ML,Grahn PJ,Calvert JS,Linde MB,Lavrov IA,Strommen JA,Beck LA,Sayenko DG,Van Straaten MG,Drubach DI,Veith DD,Thoreson AR,Lopez C,Gerasimenko YP,Edgerton VR,Lee KH,Zhao KD

更新日期：2018-12-01 00:00:00

abstract：:Cytochrome P450 3A4 is an important mediator of drug catabolism that can be regulated by the steroid and xenobiotic receptor (SXR). We show here that SXR also regulates drug efflux by activating expression of the gene MDR1, which encodes the protein P-glycoprotein (ABCB1). Paclitaxel (Taxol), a commonly used chemother...

journal_title：Nature medicine

authors： Synold TW,Dussault I,Forman BM

更新日期：2001-05-01 00:00:00

abstract：:We report the development of a new combinatorial approach that allows for peptide-mediated selective tissue targeting of nuclear hormone pharmacology while eliminating adverse effects in other tissues. Specifically, we report the development of a glucagon-like peptide-1 (GLP-1)-estrogen conjugate that has superior sex...

journal_title：Nature medicine

authors： Finan B,Yang B,Ottaway N,Stemmer K,Müller TD,Yi CX,Habegger K,Schriever SC,García-Cáceres C,Kabra DG,Hembree J,Holland J,Raver C,Seeley RJ,Hans W,Irmler M,Beckers J,de Angelis MH,Tiano JP,Mauvais-Jarvis F,Perez-Ti

更新日期：2012-12-01 00:00:00

abstract：:Activation of the zinc-finger transcription factor early growth response (Egr)-1, initially linked to developmental processes, is shown here to function as a master switch activated by ischemia to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability. Chemokine, adhesion ...

journal_title：Nature medicine

authors： Yan SF,Fujita T,Lu J,Okada K,Shan Zou Y,Mackman N,Pinsky DJ,Stern DM

更新日期：2000-12-01 00:00:00

abstract：:Much effort has been devoted to the design of vaccines that induce adaptive cellular immunity, in particular CD8+ T cells, which have a central role in the host response to viral infections and cancers. To date, however, the development of effective T cell vaccines remains elusive. This is due, in part, to the lack of...

journal_title：Nature medicine

authors： Appay V,Douek DC,Price DA

更新日期：2008-06-01 00:00:00

abstract：:Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors....

journal_title：Nature medicine

authors： Davies H,Glodzik D,Morganella S,Yates LR,Staaf J,Zou X,Ramakrishna M,Martin S,Boyault S,Sieuwerts AM,Simpson PT,King TA,Raine K,Eyfjord JE,Kong G,Borg Å,Birney E,Stunnenberg HG,van de Vijver MJ,Børresen-Dale AL,Ma

更新日期：2017-04-01 00:00:00

abstract：:Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs)...

journal_title：Nature medicine

authors： Cañadas I,Thummalapalli R,Kim JW,Kitajima S,Jenkins RW,Christensen CL,Campisi M,Kuang Y,Zhang Y,Gjini E,Zhang G,Tian T,Sen DR,Miao D,Imamura Y,Thai T,Piel B,Terai H,Aref AR,Hagan T,Koyama S,Watanabe M,Baba H,

更新日期：2018-08-01 00:00:00

abstract：:Pten is an important phosphatase, suppressing the phosphatidylinositol-3 kinase/Akt pathway. Here, we generated adipose-specific Pten-deficient (AdipoPten-KO) mice, using newly generated Acdc promoter-driven Cre transgenic mice. AdipoPten-KO mice showed lower body and adipose tissue weights despite hyperphagia and enh...

journal_title：Nature medicine

authors： Komazawa N,Matsuda M,Kondoh G,Mizunoya W,Iwaki M,Takagi T,Sumikawa Y,Inoue K,Suzuki A,Mak TW,Nakano T,Fushiki T,Takeda J,Shimomura I

更新日期：2004-11-01 00:00:00

abstract：:The notoriously drug-resistant bug MRSA has made headlines for years, but a whole other class of bacteria may prove even more troublesome. These microbes, Gram-negative bacteria, are increasingly a threat--and yet not a single late-stage drug in development specifically targets them. Christian Torres follows one man's...

journal_title：Nature medicine

authors： Torres C

更新日期：2010-06-01 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：:The role of KRAS, when activated through canonical mutations, has been well established in cancer1. Here we explore a secondary means of KRAS activation in cancer: focal high-level amplification of the KRAS gene in the absence of coding mutations. These amplifications occur most commonly in esophageal, gastric and ova...

journal_title：Nature medicine

authors： Wong GS,Zhou J,Liu JB,Wu Z,Xu X,Li T,Xu D,Schumacher SE,Puschhof J,McFarland J,Zou C,Dulak A,Henderson L,Xu P,O'Day E,Rendak R,Liao WL,Cecchi F,Hembrough T,Schwartz S,Szeto C,Rustgi AK,Wong KK,Diehl JA,Jen

更新日期：2018-07-01 00:00:00

abstract：:The N-terminal fragment of prolactin (16K PRL) inhibits tumor growth by impairing angiogenesis, but the underlying mechanisms are unknown. Here, we found that 16K PRL binds the fibrinolytic inhibitor plasminogen activator inhibitor-1 (PAI-1), which is known to contextually promote tumor angiogenesis and growth. Loss o...

journal_title：Nature medicine

authors： Bajou K,Herkenne S,Thijssen VL,D'Amico S,Nguyen NQ,Bouché A,Tabruyn S,Srahna M,Carabin JY,Nivelles O,Paques C,Cornelissen I,Lion M,Noel A,Gils A,Vinckier S,Declerck PJ,Griffioen AW,Dewerchin M,Martial JA,Carmeliet

更新日期：2014-07-01 00:00:00

abstract：:To better understand genetic alterations in oral premalignant lesions, we examined 84 oral leukoplakia samples from 37 patients who had been enrolled in a chemoprevention trial. The samples were analyzed for two microsatellite markers located at chromosomes 9p21 and 3p14. Loss of heterozygosity (LOH) at either or both...

journal_title：Nature medicine

authors： Mao L,Lee JS,Fan YH,Ro JY,Batsakis JG,Lippman S,Hittelman W,Hong WK

更新日期：1996-06-01 00:00:00

abstract：:The skin protects mammals from insults, infection and dehydration and enables thermoregulation and sensory perception. Various skin-resident cells carry out these diverse functions. Constant turnover of cells and healing upon injury necessitate multiple reservoirs of stem cells. Thus, the skin provides a model for stu...

journal_title：Nature medicine

authors： Hsu YC,Li L,Fuchs E

更新日期：2014-08-01 00:00:00

abstract：:Infections are thought to be important in the pathogenesis of many heart diseases. Coxsackievirus B3 (CVB3) has been linked to chronic dilated cardiomyopathy, a common cause of progressive heart disease, heart failure and sudden death. We show here that the sarcoma (Src) family kinase Lck (p56lck) is required for effi...

journal_title：Nature medicine

authors： Liu P,Aitken K,Kong YY,Opavsky MA,Martino T,Dawood F,Wen WH,Kozieradzki I,Bachmaier K,Straus D,Mak TW,Penninger JM

更新日期：2000-04-01 00:00:00

abstract：:Excitotoxic neuronal damage caused by overactivation of N-methyl-D-aspartate glutamate receptors (NMDARs) is thought to be a principal cause of neuronal loss after stroke and brain trauma. Here we report that activation of sterol regulatory element binding protein-1 (SREBP-1) transcription factor in affected neurons i...

journal_title：Nature medicine

authors： Taghibiglou C,Martin HG,Lai TW,Cho T,Prasad S,Kojic L,Lu J,Liu Y,Lo E,Zhang S,Wu JZ,Li YP,Wen YH,Imm JH,Cynader MS,Wang YT

更新日期：2009-12-01 00:00:00

abstract：:The HIV-1-specific cytotoxic T lymphocyte (CTL) response is temporally associated with the decline in viremia during primary HIV-1 infection, but definitive evidence that it is of importance in virus containment has been lacking. Here we show that in a patient whose early CTL response was focused on a highly immunodom...

journal_title：Nature medicine

authors： Borrow P,Lewicki H,Wei X,Horwitz MS,Peffer N,Meyers H,Nelson JA,Gairin JE,Hahn BH,Oldstone MB,Shaw GM

更新日期：1997-02-01 00:00:00

abstract：:The ability of the human immune system to respond to vaccination declines with age. We identified an age-associated defect in T cell receptor (TCR)-induced extracellular signal-regulated kinase (ERK) phosphorylation in naive CD4(+) T cells, whereas other signals, such as ζ chain-associated protein kinase 70 (ZAP70) an...

journal_title：Nature medicine

authors： Li G,Yu M,Lee WW,Tsang M,Krishnan E,Weyand CM,Goronzy JJ

更新日期：2012-10-01 00:00:00

abstract：:Immune-checkpoint blockade (ICB) has demonstrated efficacy in many tumor types, but predictors of responsiveness to anti-PD1 ICB are incompletely characterized. In this study, we analyzed a clinically annotated cohort of patients with melanoma (n = 144) treated with anti-PD1 ICB, with whole-exome and whole-transcripto...

journal_title：Nature medicine

authors： Liu D,Schilling B,Liu D,Sucker A,Livingstone E,Jerby-Arnon L,Zimmer L,Gutzmer R,Satzger I,Loquai C,Grabbe S,Vokes N,Margolis CA,Conway J,He MX,Elmarakeby H,Dietlein F,Miao D,Tracy A,Gogas H,Goldinger SM,Utikal J

更新日期：2019-12-01 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：:Autosomal dominant polycystic kidney disease is an important cause of end-stage renal disease, for which there is no proven therapy. Mutations in PKD1 (the gene encoding polycystin-1) are the principal cause of this disease. The disease begins in utero and is slowly progressive, but it is not known whether cystogenesi...

journal_title：Nature medicine

authors： Piontek K,Menezes LF,Garcia-Gonzalez MA,Huso DL,Germino GG

更新日期：2007-12-01 00:00:00