Abstract:
:Technologies are needed to map and image biological barriers in vivo that limit solid tumor delivery and, ultimately, the effectiveness of imaging and therapeutic agents. Here we integrate proteomic and imaging analyses of caveolae at the blood-tumor interface to discover an active transendothelial portal to infiltrate tumors. A post-translationally modified form of annexin A1 (AnnA1) is selectively concentrated in human and rodent tumor caveolae. To follow trafficking, we generated a specific AnnA1 antibody that targets caveolae in the tumor endothelium. Intravital microscopy of caveolae-immunotargeted fluorophores even at low intravenous doses showed rapid and robust pumping across the endothelium to enter mammary, prostate and lung tumors. Within 1 h, the fluorescence signal concentrated throughout tumors to exceed the peak levels in blood. This transvascular pumping required the expression of caveolin 1 and annexin A1. Tumor uptake with other antibodies were >100-fold less. This proteomic imaging strategy reveals a unique target, antibody and caveolae pumping system for solid tumor penetration.
journal_name
Nat Medjournal_title
Nature medicineauthors
Oh P,Testa JE,Borgstrom P,Witkiewicz H,Li Y,Schnitzer JEdoi
10.1038/nm.3623subject
Has Abstractpub_date
2014-09-01 00:00:00pages
1062-8issue
9eissn
1078-8956issn
1546-170Xpii
nm.3623journal_volume
20pub_type
杂志文章相关文献
NATURE MEDICINE文献大全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
pub_type: 杂志文章
doi:10.1038/nm0498-441
更新日期:1998-04-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature medicine
pub_type: 已发布勘误
doi:10.1038/s41591-019-0562-8
更新日期:2019-09-01 00:00:00
abstract::Programmed cell death (apoptosis) seems to be the principal mechanism whereby anti-oncogenic therapies such as chemotherapy and radiation effect their responses. Resistance to apoptosis, therefore, is probably a principal mechanism whereby tumors are able to overcome these cancer therapies. The transcription factor NF...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/7410
更新日期:1999-04-01 00:00:00
abstract::Although the treatment of acute myeloid leukemia (AML) has improved substantially in the past three decades, more than half of all patients develop disease that is refractory to intensive chemotherapy. Functional genomics approaches offer a means to discover specific molecules mediating the aberrant growth and surviva...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2819
更新日期:2012-07-01 00:00:00
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
doi:10.1038/s41591-018-0104-9
更新日期:2018-07-01 00:00:00
abstract::After transplantation of primarily vascularized xenografts (Xgs), T-independent mechanisms may lead to Xg rejection before T-cell activation even takes place. The possibility of achieving T-independent xenotolerance was evaluated in nude rats that normally reject hamster cardiac Xgs within 4 days by non-T cell-mediate...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0298-173
更新日期:1998-02-01 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
pub_type: 杂志文章
doi:10.1038/nm0297-205
更新日期:1997-02-01 00:00:00
abstract::The search for immunosuppressant drugs to increase the success of organ transplantation led to the discovery of the immunophilins, proteins that interface with a range of signal transduction systems inside cells, especially in the nervous and immune systems. Here we review how these interesting molecules work and cons...
journal_title:Nature medicine
pub_type: 杂志文章,评审
doi:10.1038/nm0195-32
更新日期:1995-01-01 00:00:00
abstract::Basal cell carcinoma (BCC), the most common human cancer, results from aberrant activation of the Hedgehog signaling pathway. Although most cases of BCC are sporadic, some forms are inherited, such as Bazex-Dupré-Christol syndrome (BDCS)-a cancer-prone genodermatosis with an X-linked, dominant inheritance pattern. We ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4368
更新日期:2017-10-01 00:00:00
abstract::Hypothalamic brain-derived neurotrophic factor (BDNF) is a key element in the regulation of energy balance. Here we investigated the therapeutic efficacy of BDNF by gene transfer in mouse models of obesity and diabetes. Gene transfer of BDNF led to marked weight loss and alleviation of obesity-associated insulin resis...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.1933
更新日期:2009-04-01 00:00:00
abstract::Breast cancers are either primarily resistant to chemotherapy (intrinsic resistance), or respond to chemotherapy but later recur with a multidrug-resistant phenotype because of overexpression of the multidrug transporter P-glycoprotein. The MDR1 gene encoding P-glycoprotein may be transcriptionally regulated by a Y-bo...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0497-447
更新日期:1997-04-01 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
pub_type: 杂志文章
doi:10.1038/nm.2022
更新日期:2009-09-01 00:00:00
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
doi:10.1038/nm.2762
更新日期:2012-05-04 00:00:00
abstract::We and others have postulated that a constant number of T lymphocytes is normally maintained without regard to CD4+ or CD8+ phenotype ('blind' T-cell homeostasis). Here we confirm essentially constant T-cell levels (despite marked decline in CD4+ T cells and increase in CD8+ T cells) in homosexual men with incident hu...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0795-674
更新日期:1995-07-01 00:00:00
abstract::Exercise has numerous health-promoting effects in humans; however, individual responsiveness to exercise with regard to endurance or metabolic health differs markedly. This 'exercise resistance' is considered to be congenital, with no evident acquired causative factors. Here we show that the anti-oxidative hepatokine ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4295
更新日期:2017-04-01 00:00:00
abstract::The bromodomain and extraterminal (BET) family of proteins comprises four members-BRD2, BRD3, BRD4 and the testis-specific isoform BRDT-that largely function as transcriptional coactivators and play critical roles in various cellular processes, including the cell cycle, apoptosis, migration and invasion. BET proteins ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4378
更新日期:2017-09-01 00:00:00
abstract::A new regulatory pathway established last year allows drugs with dramatic early clinical promise to be expedited to the market quicker than ever before. To date, most of these 'breakthrough' designations have gone to cancer agents, raising the prospect of faster access to the latest lifesaving therapies for the estima...
journal_title:Nature medicine
pub_type: 新闻
doi:10.1038/nm.3245
更新日期:2013-06-01 00:00:00
abstract::HIV infection can cause extensive neuronal loss and clinically a severe dementia. The cause of the neurotoxicity remains unclear as neurons are not infected, but disturbance of glutamate-linked calcium entry has been implicated. In this study, we have shown a decrease in HIV-infected brain of the expression of mRNA an...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1195-1174
更新日期:1995-11-01 00:00:00
abstract::Diabetes, a disease in which the body does not produce or use insulin properly, is a serious global health problem. Gut polypeptides secreted in response to food intake, such as glucagon-like peptide-1 (GLP-1), are potent incretin hormones that enhance the glucose-dependent secretion of insulin from pancreatic beta ce...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1168
更新日期:2005-01-01 00:00:00
abstract::A signaling cascade is activated in podocytes to induce survival and cope with stress during advanced glomerular disease, a new study shows. The findings may also explain why the immunosuppressor sirolimus, an inhibitor of this pathway, can cause proteinuria in a subset of patients with chronic kidney disease (pages 1...
journal_title:Nature medicine
pub_type: 评论,新闻
doi:10.1038/nm.3357
更新日期:2013-10-01 00:00:00
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
doi:10.1038/s41591-018-0170-z
更新日期:2018-10-01 00:00:00
abstract::De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessin...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-019-0711-0
更新日期:2020-01-01 00:00:00
abstract::The adoptive transfer of T cells engineered with a chimeric antigen receptor (CAR) (hereafter referred to as CAR-T cells) specific for the B lymphocyte antigen CD19 has shown impressive clinical responses in patients with refractory B cell malignancies. However, the therapeutic effects of CAR-T cells that target other...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4478
更新日期:2018-03-01 00:00:00
abstract::Immunization of transgenic mouse models of Alzheimer disease using amyloid-beta peptide (Abeta) reduces both the Alzheimer disease-like neuropathology and the spatial memory impairments of these mice. However, a therapeutic trial of immunization with Abeta42 in humans was discontinued because a few patients developed ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm790
更新日期:2002-11-01 00:00:00
abstract::We show that the fraction of proliferating CD4+ lymphocytes is similar in HIV-infected subjects in the early stage of disease and in HIV-negative subjects, whereas the fraction of proliferating CD8+ lymphocytes is increased 6.8-fold in HIV-infected subjects. After initiation of antiviral therapy, there is a late incre...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0798-794
更新日期:1998-07-01 00:00:00
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
doi:10.1038/nm1127
更新日期:2004-11-01 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
pub_type: 杂志文章
doi:10.1038/nm.2963
更新日期:2012-10-01 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
pub_type: 杂志文章
doi:10.1038/79510
更新日期:2000-09-01 00:00:00
abstract::The C2 domain of synaptotagmin I, which binds to anionic phospholipids in cell membranes, was shown to bind to the plasma membrane of apoptotic cells by both flow cytometry and confocal microscopy. Conjugation of the protein to superparamagnetic iron oxide nanoparticles allowed detection of this binding using magnetic...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1101-1241
更新日期:2001-11-01 00:00:00
abstract::Mobilization of hematopoietic stem and progenitor cells (HSPCs) from bone marrow into peripheral blood by the cytokine granulocyte colony-stimulating factor (G-CSF) has become the preferred source of HSPCs for stem cell transplants. However, G-CSF fails to mobilize sufficient numbers of stem cells in up to 10% of dono...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2217
更新日期:2010-10-01 00:00:00