Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization.


: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 blood vessels in several vascular beds including the retina, blockade of this downstream adhesion receptor system was investigated. In a mouse model of hypoxia-induced retinal neovascularization twice daily administration of 1 to 20 mg cyclic alpha v-integrin antagonist peptide per kilogram of body weight reduced capillary proliferation in a dose-dependent fashion--maximum 76%--without obvious side effects. A cyclic control peptide displayed no inhibitory effect on neovascularization. These findings indicate that systemic application of vitronectin receptor antagonists appears to be clinically feasible and is efficient in preventing retinal neovascularization and superior to cytokine-blocking strategies.


Nat Med


Nature medicine


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




Has Abstract


1996-05-01 00:00:00












  • IKK-beta links inflammation to obesity-induced insulin resistance.

    abstract::Inflammation may underlie the metabolic disorders of insulin resistance and type 2 diabetes. IkappaB kinase beta (IKK-beta, encoded by Ikbkb) is a central coordinator of inflammatory responses through activation of NF-kappaB. To understand the role of IKK-beta in insulin resistance, we used mice lacking this enzyme in...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Arkan MC,Hevener AL,Greten FR,Maeda S,Li ZW,Long JM,Wynshaw-Boris A,Poli G,Olefsky J,Karin M

    更新日期:2005-02-01 00:00:00

  • Inhibition of cellular ras prevents smooth muscle cell proliferation after vascular injury in vivo.

    abstract::Proliferation of smooth muscle cells of the arterial wall in response to local injury is an important aetiologic factor of vascular proliferative disorders such as atherosclerosis and restenosis after angioplasty. Ras proteins are key transducers of mitogenic signals from membrane to nucleus in many cell types. We inv...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Indolfi C,Avvedimento EV,Rapacciuolo A,Di Lorenzo E,Esposito G,Stabile E,Feliciello A,Mele E,Giuliano P,Condorelli G

    更新日期:1995-06-01 00:00:00

  • Short interfering RNA (siRNA) targeting the Lyn kinase induces apoptosis in primary, and drug-resistant, BCR-ABL1(+) leukemia cells.

    abstract::We studied the effects of Lyn ablation on the survival of drug-resistant chronic myelogenous leukemia (CML) blast crisis cells using siRNA. Lyn siRNA reduced Lyn protein in both normal hematopoietic cells and BCR-ABL1-expressing (BCR-ABL1(+)) blasts by 80-95%. Within 48 h, siRNA-treated BCR-ABL1(+) blasts underwent ap...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Ptasznik A,Nakata Y,Kalota A,Emerson SG,Gewirtz AM

    更新日期:2004-11-01 00:00:00

  • Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke.

    abstract::Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme gamma-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apopto...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Arumugam TV,Chan SL,Jo DG,Yilmaz G,Tang SC,Cheng A,Gleichmann M,Okun E,Dixit VD,Chigurupati S,Mughal MR,Ouyang X,Miele L,Magnus T,Poosala S,Granger DN,Mattson MP

    更新日期:2006-06-01 00:00:00

  • Targeted estrogen delivery reverses the metabolic syndrome.

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    journal_title:Nature medicine

    pub_type: 杂志文章


    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

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  • TLR4 enhances TGF-beta signaling and hepatic fibrosis.

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    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Seki E,De Minicis S,Osterreicher CH,Kluwe J,Osawa Y,Brenner DA,Schwabe RF

    更新日期:2007-11-01 00:00:00

  • Release and activation of platelet latent TGF-beta in blood clots during dissolution with plasmin.

    abstract::Transforming growth factor beta 1 (TGF-beta 1) is a platelet-derived cytokine involved in both normal wound healing and scarring. We show that human platelets contain two pools of latent TGF-beta 1, which constitute more than 95% of the total TGF-beta assayed in whole platelets. During clotting, one pool, the large la...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Grainger DJ,Wakefield L,Bethell HW,Farndale RW,Metcalfe JC

    更新日期:1995-09-01 00:00:00

  • Human lupus T cells resist inactivation and escape death by upregulating COX-2.

    abstract::Autoimmune T-helper cells drive pathogenic autoantibody production in systemic lupus erythematosus (SLE), but the mechanisms maintaining those T cells are unknown. Autoreactive T cells are normally eliminated by functional inactivation (anergy) and activation-induced cell death (AICD) or apoptosis through death recept...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Xu L,Zhang L,Yi Y,Kang HK,Datta SK

    更新日期:2004-04-01 00:00:00

  • Differential requirement for CD18 in T-helper effector homing.

    abstract::To understand the integrin requirements of T-helper (T(H)) effector subsets, we investigated the contribution of CD18 (beta(2) integrin) to T(H)1 and T(H)2 function in vitro and in relevant disease models. CD18-deficient (Itgb2(-/-)) T cells showed largely normal in vitro function. Compared with wild-type mice, Itgb2(...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Lee SH,Prince JE,Rais M,Kheradmand F,Shardonofsky F,Lu H,Beaudet AL,Smith CW,Soong L,Corry DB

    更新日期:2003-10-01 00:00:00

  • Frequent microsatellite alterations at chromosomes 9p21 and 3p14 in oral premalignant lesions and their value in cancer risk assessment.

    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

    pub_type: 杂志文章


    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

  • Role of NMDA receptor-dependent activation of SREBP1 in excitotoxic and ischemic neuronal injuries.

    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

    pub_type: 杂志文章


    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

  • Senolytics improve physical function and increase lifespan in old age.

    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

    pub_type: 杂志文章


    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

  • Author Correction: Metformin reverses established lung fibrosis in a bleomycin model.

    abstract::In the version of this article originally published, a grant was omitted from the Acknowledgements section. The following sentence should have been included: "R.B.M. was supported by a Department of Veterans Affairs Merit Award (5I01BX003272)." The error has been corrected in the HTML and PDF versions of this article....

    journal_title:Nature medicine

    pub_type: 已发布勘误


    authors: Rangarajan S,Bone NB,Zmijewska AA,Jiang S,Park DW,Bernard K,Locy ML,Ravi S,Deshane J,Mannon RB,Abraham E,Darley-Usmar V,Thannickal VJ,Zmijewski JW

    更新日期:2018-10-01 00:00:00

  • Type II monocytes modulate T cell-mediated central nervous system autoimmune disease.

    abstract::Treatment with glatiramer acetate (GA, copolymer-1, Copaxone), a drug approved for multiple sclerosis (MS), in a mouse model promoted development of anti-inflammatory type II monocytes, characterized by increased secretion of interleukin (IL)-10 and transforming growth factor (TGF)-beta, and decreased production of IL...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Weber MS,Prod'homme T,Youssef S,Dunn SE,Rundle CD,Lee L,Patarroyo JC,Stüve O,Sobel RA,Steinman L,Zamvil SS

    更新日期:2007-08-01 00:00:00

  • Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice.

    abstract::The structure and function of blood vessels adapt to environmental changes such as physical development and exercise. This phenomenon is based on the ability of the endothelial cells to sense and respond to blood flow; however, the underlying mechanisms remain unclear. Here we show that the ATP-gated P2X4 ion channel,...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Yamamoto K,Sokabe T,Matsumoto T,Yoshimura K,Shibata M,Ohura N,Fukuda T,Sato T,Sekine K,Kato S,Isshiki M,Fujita T,Kobayashi M,Kawamura K,Masuda H,Kamiya A,Ando J

    更新日期:2006-01-01 00:00:00

  • Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma.

    abstract::Glioblastoma is the most common primary central nervous system malignancy and has a poor prognosis. Standard first-line treatment, which includes surgery followed by adjuvant radio-chemotherapy, produces only modest benefits to survival1,2. Here, to explore the feasibility, safety and immunobiological effects of PD-1 ...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Schalper KA,Rodriguez-Ruiz ME,Diez-Valle R,López-Janeiro A,Porciuncula A,Idoate MA,Inogés S,de Andrea C,López-Diaz de Cerio A,Tejada S,Berraondo P,Villarroel-Espindola F,Choi J,Gúrpide A,Giraldez M,Goicoechea I,Gallego Pe

    更新日期:2019-03-01 00:00:00

  • Identification of the prion protein allotypes which accumulate in the brain of sporadic and familial Creutzfeldt-Jakob disease patients.

    abstract::A characteristic feature of Creutzfeldt-Jakob disease (CJD) is the accumulation in the brain of the amyloid protease-resistant protein PrPres. PrPres derives from a host-encoded, protease-sensitive isoform, PrPsen. Mutations of this protein are linked to familial variants of the disease, and the presence of a methioni...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Silvestrini MC,Cardone F,Maras B,Pucci P,Barra D,Brunori M,Pocchiari M

    更新日期:1997-05-01 00:00:00

  • Specific peptide interference reveals BCL6 transcriptional and oncogenic mechanisms in B-cell lymphoma cells.

    abstract::The BTB/POZ transcriptional repressor and candidate oncogene BCL6 is frequently misregulated in B-cell lymphomas. The interface through which the BCL6 BTB domain mediates recruitment of the SMRT, NCoR and BCoR corepressors was recently identified. To determine the contribution of this interface to BCL6 transcriptional...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Polo JM,Dell'Oso T,Ranuncolo SM,Cerchietti L,Beck D,Da Silva GF,Prive GG,Licht JD,Melnick A

    更新日期:2004-12-01 00:00:00

  • Neonatal mouse immunity against group B streptococcal infection by maternal vaccination with recombinant anti-idiotypes.

    abstract::We investigated whether immunization with recombinant anti-idiotypic antibody fragments mimicking the conformation of the capsular antigen can protect against infection by group B streptococcus, an important neonatal pathogen. Single-chain fragment-variable anti-idiotypes competed with the type III carbohydrate for bi...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Magliani W,Polonelli L,Conti S,Salati A,Rocca PF,Cusumano V,Mancuso G,Teti G

    更新日期:1998-06-01 00:00:00

  • Mechanisms of NAFLD development and therapeutic strategies.

    abstract::There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosi...

    journal_title:Nature medicine

    pub_type: 杂志文章,评审


    authors: Friedman SL,Neuschwander-Tetri BA,Rinella M,Sanyal AJ

    更新日期:2018-07-01 00:00:00

  • Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease.

    abstract::One hallmark of Alzheimer disease is the accumulation of amyloid beta-peptide in the brain and its deposition as plaques. Mice transgenic for an amyloid beta precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor promoter (PDAPP mice), which overexpress one of the disease-linked mutant forms...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Bard F,Cannon C,Barbour R,Burke RL,Games D,Grajeda H,Guido T,Hu K,Huang J,Johnson-Wood K,Khan K,Kholodenko D,Lee M,Lieberburg I,Motter R,Nguyen M,Soriano F,Vasquez N,Weiss K,Welch B,Seubert P,Schenk D,Yednock

    更新日期:2000-08-01 00:00:00

  • RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain.

    abstract::Amyloid-beta peptide (Abeta) interacts with the vasculature to influence Abeta levels in the brain and cerebral blood flow, providing a means of amplifying the Abeta-induced cellular stress underlying neuronal dysfunction and dementia. Systemic Abeta infusion and studies in genetically manipulated mice show that Abeta...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Deane R,Du Yan S,Submamaryan RK,LaRue B,Jovanovic S,Hogg E,Welch D,Manness L,Lin C,Yu J,Zhu H,Ghiso J,Frangione B,Stern A,Schmidt AM,Armstrong DL,Arnold B,Liliensiek B,Nawroth P,Hofman F,Kindy M,Stern D,Zlokov

    更新日期:2003-07-01 00:00:00

  • Translational control of tumor immune escape via the eIF4F-STAT1-PD-L1 axis in melanoma.

    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

    pub_type: 杂志文章


    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

  • King of hearts: a splicing factor rules cardiac proteins.

    abstract::Alternative splicing ensures the expression of functionally diverse proteins from individual genes; however, aberrant mRNA splicing is associated with various conditions, including heart disease. A recent study provides new mechanistic insights into heart failure by showing that a human cardiomyopathy-linked mutation ...

    journal_title:Nature medicine

    pub_type: 评论,杂志文章


    authors: Linke WA,Bücker S

    更新日期:2012-05-04 00:00:00

  • Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound.

    abstract::The tumor suppressor p53 inhibits tumor growth primarily through its ability to induce apoptosis. Mutations in p53 occur in at least 50% of human tumors. We hypothesized that reactivation of mutant p53 in such tumors should trigger massive apoptosis and eliminate the tumor cells. To test this, we screened a library of...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Bykov VJ,Issaeva N,Shilov A,Hultcrantz M,Pugacheva E,Chumakov P,Bergman J,Wiman KG,Selivanova G

    更新日期:2002-03-01 00:00:00

  • PAI-1 mediates the antiangiogenic and profibrinolytic effects of 16K prolactin.

    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

    pub_type: 杂志文章


    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

  • Adenosine is crucial for deep brain stimulation-mediated attenuation of tremor.

    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

    pub_type: 杂志文章


    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

  • The effects of tobacco control policies on global smoking prevalence.

    abstract::Substantial global effort has been devoted to curtailing the tobacco epidemic over the past two decades, especially after the adoption of the Framework Convention on Tobacco Control1 by the World Health Organization in 2003. In 2015, in recognition of the burden resulting from tobacco use, strengthened tobacco control...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Flor LS,Reitsma MB,Gupta V,Ng M,Gakidou E

    更新日期:2021-01-21 00:00:00

  • Passive immunization with a human monoclonal antibody protects hu-PBL-SCID mice against challenge by primary isolates of HIV-1.

    abstract::How well antibodies can protect against disease due to HIV-1 infection remains a pivotal but unresolved issue with important implications for vaccine design and the use of prophylactic antibody to prevent infection after accidental exposure to the virus and to interrupt transmission of virus from mother to child. Stro...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Gauduin MC,Parren PW,Weir R,Barbas CF,Burton DR,Koup RA

    更新日期:1997-12-01 00:00:00

  • Combined treatment with oral metronidazole and N-acetylcysteine is effective in ethylmalonic encephalopathy.

    abstract::Ethylmalonic encephalopathy is caused by mutations in ETHE1, a mitochondrial matrix sulfur dioxygenase, leading to failure to detoxify sulfide, a product of intestinal anaerobes and, in trace amounts, tissues. Metronidazole, a bactericide, or N-acetylcysteine, a precursor of sulfide-buffering glutathione, substantiall...

    journal_title:Nature medicine

    pub_type: 杂志文章


    authors: Viscomi C,Burlina AB,Dweikat I,Savoiardo M,Lamperti C,Hildebrandt T,Tiranti V,Zeviani M

    更新日期:2010-08-01 00:00:00