Abstract:
:The invasive nature of glioblastoma (GBM) represents a major clinical challenge contributing to poor outcomes. Invasion of GBM into healthy tissue restricts chemotherapeutic access and complicates surgical resection. Here, we test the hypothesis that an effective anti-invasive agent can "contain" GBM and increase the efficacy of chemotherapy. We report a new anti-invasive small molecule, Imipramine Blue (IB), which inhibits invasion of glioma in vitro when tested against several models. IB inhibits NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-mediated reactive oxygen species generation and alters expression of actin regulatory elements. In vivo, liposomal IB (nano-IB) halts invasion of glioma, leading to a more compact tumor in an aggressively invasive RT2 syngeneic astrocytoma rodent model. When nano-IB therapy was followed by liposomal doxorubicin (nano-DXR) chemotherapy, the combination therapy prolonged survival compared to nano-IB or nano-DXR alone. Our data demonstrate that nano-IB-mediated containment of diffuse glioma enhanced the efficacy of nano-DXR chemotherapy, demonstrating the promise of an anti-invasive compound as an adjuvant treatment for glioma.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Munson JM,Fried L,Rowson SA,Bonner MY,Karumbaiah L,Diaz B,Courtneidge SA,Knaus UG,Brat DJ,Arbiser JL,Bellamkonda RVdoi
10.1126/scitranslmed.3003016subject
Has Abstractpub_date
2012-03-28 00:00:00pages
127ra36issue
127eissn
1946-6234issn
1946-6242pii
4/127/127ra36journal_volume
4pub_type
杂志文章abstract::Aspirin use reduces the risk of colorectal neoplasia, at least in part, through inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase 2)-related pathways. Hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide) (15-PGDH, HPGD) is down-regulated in colorectal cancers and functions...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3008481
更新日期:2014-04-23 00:00:00
abstract::Cancer-associated thrombocytosis and high concentrations of circulating transforming growth factor-β1 (TGF-β1) are frequently observed in patients with progressive cancers. Using genetic and pharmacological approaches, we show a direct link between thrombin catalytic activity and release of mature TGF-β1 from platelet...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aay4860
更新日期:2020-01-08 00:00:00
abstract::Forty years ago, Judah Folkman predicted that tumor growth is dependent on angiogenesis and that inhibiting this process might be a new strategy for cancer therapy. This hypothesis formed the foundation of a new field of research that represents an excellent example of how a groundbreaking scientific discovery can be ...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.3003149
更新日期:2011-12-21 00:00:00
abstract::Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB), and key TB antimicrobials, including rifampin, have restricted brain penetration. A lack of reliable data on intralesional drug biodistribution in infected tissues has limited pharmacokinetic (PK) modeling efforts to optimize TBM treatments. Curr...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aau0965
更新日期:2018-12-05 00:00:00
abstract::The elevation of carbon dioxide (CO2) in tissues and the bloodstream (hypercapnia) occurs in patients with severe lung diseases, including chronic obstructive pulmonary disease (COPD). Whereas hypercapnia has been recognized as a marker of COPD severity, a role for hypercapnia in disease pathogenesis remains unclear. ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aat1662
更新日期:2018-09-05 00:00:00
abstract::Rapid advancements in the field of stem cell biology have led to many current efforts to exploit stem cells as therapeutic agents in regenerative medicine. However, current ex vivo cell manipulations common to most regenerative approaches create a variety of technical and regulatory hurdles to their clinical translati...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3008234
更新日期:2014-05-28 00:00:00
abstract::Magnetic resonance imaging (MRI) is a powerful diagnostic tool, but its use is restricted to the scanner suite. Here, we demonstrate that a bedside nuclear magnetic resonance (NMR) sensor can assess fluid status changes in individuals at a fraction of the time and cost compared to MRI. Our study recruited patients wit...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aau1749
更新日期:2019-07-24 00:00:00
abstract::Advances in health information technology and electronic medical records have the tremendous potential to accelerate translational and clinical research. However, privacy concerns threaten to be a rate-limiting factor. By recognizing and responding to patient privacy concerns, policy-makers, researchers, and informati...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3002037
更新日期:2011-02-09 00:00:00
abstract::The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by acute and chronic graft-versus-host disease (GVHD). The impact of obesity on allo-HSCT outcomes is poorly understood. Here, we report that obesity had a negative and selective impact on acute gut GVHD after allo-HSCT in mice w...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aay7713
更新日期:2020-11-25 00:00:00
abstract::Meibomian glands (MGs) are sebaceous glands of the eyelid margin that secrete lipids needed to avert tear evaporation and to help maintain ocular surface homeostasis. Obstruction of MGs or other forms of MG dysfunction can promote chronic diseases of the ocular surface. Although chronic eyelid inflammation, such as al...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aas9164
更新日期:2018-07-25 00:00:00
abstract::Sporadic inclusion body myositis (sIBM) is the commonest severe myopathy in patients more than 50 years of age. Previous therapeutic trials have targeted the inflammatory features of sIBM but all have failed. Because protein dyshomeostasis may also play a role in sIBM, we tested the effects of targeting this feature o...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aad4583
更新日期:2016-03-23 00:00:00
abstract::Variants in the leucine-rich repeat kinase-2 (LRRK2) gene are associated with Parkinson's disease, leprosy, and Crohn's disease, three disorders with inflammation as an important component. Because of its high expression in granulocytes and CD68-positive cells, LRRK2 may have a function in innate immunity. We tested t...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aas9292
更新日期:2019-09-25 00:00:00
abstract::Elucidating the factors that impinge on the stability of bacterial communities in the vagina may help in predicting the risk of diseases that affect women's health. Here, we describe the temporal dynamics of the composition of vaginal bacterial communities in 32 reproductive-age women over a 16-week period. The analys...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3003605
更新日期:2012-05-02 00:00:00
abstract::Thanks to the revolutions in information technology, human "-omics" research, and intricate medical device development, academic health centers (AHCs) now have an unparalleled potential to become translational engines that both generate basic science advances and then translate them into human studies and, ultimately,...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3000124
更新日期:2009-10-07 00:00:00
abstract::In populations that have not been selected for family history of disease, it is unclear how commonly pathogenic variants (PVs) in disease-associated genes for rare Mendelian conditions are found and how often they are associated with clinical features of these conditions. We conducted independent, prospective analyses...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aag2367
更新日期:2016-11-09 00:00:00
abstract::SORLA/SORL1 is a unique neuronal sorting receptor for the amyloid precursor protein that has been causally implicated in both sporadic and autosomal dominant familial forms of Alzheimer's disease (AD). Brain concentrations of SORLA are inversely correlated with amyloid-β (Aβ) in mouse models and AD patients, suggestin...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3007747
更新日期:2014-02-12 00:00:00
abstract::Optogenetics offers promise for dissecting the complex neural circuits of the spinal cord and peripheral nervous system and has therapeutic potential for addressing unmet clinical needs. Much progress has been made to enable optogenetic control in normal and disease states, both in proof-of-concept and mechanistic stu...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.aad7577
更新日期:2016-05-04 00:00:00
abstract::Pluripotent stem cells are a scalable source of pancreatic cells for transplantation into patients with diabetes. Here, we describe how the field is gaining momentum toward a β cell replacement therapy. ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaa9359
更新日期:2015-12-02 00:00:00
abstract::Patients undergoing surgical resection of primary breast tumors confront a risk for metastatic recurrence that peaks sharply 12 to 18 months after surgery. The cause of early metastatic relapse in breast cancer has long been debated, with many ascribing these relapses to the natural progression of the disease. Others ...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aan3464
更新日期:2018-04-11 00:00:00
abstract::Retinal pigment epithelium (RPE) dysfunction and loss are a hallmark of non-neovascular age-related macular degeneration (NNAMD). Without the RPE, a majority of overlying photoreceptors ultimately degenerate, leading to severe, progressive vision loss. Clinical and histological studies suggest that RPE replacement str...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aao4097
更新日期:2018-04-04 00:00:00
abstract::Asthma is a clinically heterogeneous genetic disease, and its pathogenesis is incompletely understood. Genome-wide association studies link ORM (yeast)-Like protein isoform 3 [corrected] (ORMDL3), a member of the ORM gene family, to nonallergic childhood-onset asthma. Orm proteins negatively regulate sphingolipid (SL)...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3005765
更新日期:2013-05-22 00:00:00
abstract::Pathological angiogenesis is the hallmark of diseases such as cancer and retinopathies. Although tissue hypoxia and inflammation are recognized as central drivers of vessel growth, relatively little is known about the process that bridges the two. In a mouse model of ischemic retinopathy, we found that hypoxic regions...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaf9440
更新日期:2016-10-26 00:00:00
abstract::Pathogenic immunoglobulin G (IgG) autoantibodies characterize some human autoimmune diseases; their high concentration and long half-life are dependent on recycling by the neonatal Fc receptor (FcRn). Inhibition of FcRn is an attractive new treatment concept for IgG-mediated autoimmune diseases. Rozanolixizumab (UCB76...
journal_title:Science translational medicine
pub_type: 杂志文章,随机对照试验
doi:10.1126/scitranslmed.aan1208
更新日期:2017-11-01 00:00:00
abstract::Nipah virus is an emerging pathogen in the Paramyxoviridae family. Upon transmission of Nipah virus from its natural reservoir, Pteropus spp. fruit bats, to humans, it causes respiratory and neurological disease with a case-fatality rate about 70%. Human-to-human transmission has been observed during Nipah virus outbr...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aau9242
更新日期:2019-05-29 00:00:00
abstract::Cooperative oncogenic effects resulting from the loss of PTEN and overexpression of MYC overcome the deleterious effects of endoplasmic reticulum stress not only to promote the growth of aggressive prostate cancer but also to expose a new therapy target for this disease (Nguyen et al, this issue). ...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.aat3975
更新日期:2018-05-02 00:00:00
abstract::In current clinical practice, uterine contractions are monitored via a tocodynamometer or an intrauterine pressure catheter, both of which provide crude information about contractions. Although electrohysterography/electromyography can measure uterine electrical activity, this method lacks spatial specificity and thus...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aau1428
更新日期:2019-03-13 00:00:00
abstract::Rapidly spreading antibiotic resistance and the low discovery rate of new antimicrobial compounds demand more effective strategies for early drug discovery. One bottleneck in the drug discovery pipeline is the identification of the modes of action (MoAs) of new compounds. We have developed a rapid systematic metabolom...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aal3973
更新日期:2018-02-21 00:00:00
abstract::Clinical diagnostic tools requiring direct sample testing cannot be applied to infections deep within the body, and clinically available imaging tools lack specificity. New approaches are needed for early diagnosis and monitoring of bacterial infections and rapid detection of drug-resistant organisms. Molecular imagin...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.aax8251
更新日期:2019-09-04 00:00:00
abstract::Buprenorphine, a synthetic opioid that acts at both μ and κ opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at μ opioid receptors raises its potential for creating opioid dependence in non-opioid-dependent cocaine abusers. Here, we te...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3003948
更新日期:2012-08-08 00:00:00
abstract::Because of the well-established therapeutic benefit of boosting antitumor responses through blockade of the T cell inhibitory receptor PD-1, it has been proposed that PD-1 blockade could also be useful in infectious disease settings, including Mycobacterium tuberculosis (Mtb) infection. However, in preclinical models,...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aat2702
更新日期:2019-01-16 00:00:00