Abstract:
:Medulloblastomas often activate Hedgehog signaling inappropriately. The finding that mutations in components of this pathway are present only in few tumors suggests that additional genetic or epigenetic lesions can also lead to Hedgehog dysregulation. Chromosome 17p deletion, the most frequently detected genetic lesion in medulloblastoma, has recently been identified as a cause of unrestrained Hedgehog signaling. Such a deletion leads to the loss of REN(KCTD11), a novel Hedgehog antagonist, thus removing a checkpoint of Hedgehog-dependent events during cerebellum development and tumorigenesis. The disruption of additional Hedgehog modulators that map to 17p suggests a rationale for a multitargeted therapeutic strategy aimed at interrupting the cooperative activation of the Hedgehog pathway.
journal_name
Trends Mol Medjournal_title
Trends in molecular medicineauthors
Ferretti E,De Smaele E,Di Marcotullio L,Screpanti I,Gulino Adoi
10.1016/j.molmed.2005.10.005keywords:
subject
Has Abstractpub_date
2005-12-01 00:00:00pages
537-45issue
12eissn
1471-4914issn
1471-499Xpii
S1471-4914(05)00239-Xjournal_volume
11pub_type
杂志文章,评审abstract::The Hedgehog (Hh) cascade controls cell proliferation, differentiation and patterning of tissues during embryogenesis but is largely suppressed in the adult. The Hh pathway can become reactivated in cancer. Here, we assimilate data from recent studies to understand how and when the Hh pathway is turned on to aid the n...
journal_title:Trends in molecular medicine
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abstract::Recurrent pregnancy loss (RPL), which occurs in 0.5%-1% of total pregnancies, is usually defined as three or more consecutive spontaneous abortions before 20 weeks of gestation. Although an immunology-based etiology underlying unexplained RPL has been demonstrated, the exact molecular mechanisms are still poorly under...
journal_title:Trends in molecular medicine
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abstract::Innate immunity is the first line of defense against invading pathogens. A family of Toll-like receptors (TLRs) acts as primary sensors that detect a wide variety of microbial components and elicit innate immune responses. All TLR signaling pathways culminate in activation of the transcription factor nuclear factor-ka...
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abstract::H(2)O(2) is a reactive oxygen species that has drawn much interest because of its role as a second messenger in receptor-mediated signaling. Mammalian 2-Cys peroxiredoxins have been shown to eliminate efficiently the H(2)O(2) generated in response to receptor stimulation. 2-Cys peroxiredoxins are members of a novel pe...
journal_title:Trends in molecular medicine
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abstract::Senescent cells drive ageing and the associated loss in health and lifespan. Whether this is mediated by systemic signalling remained unclear. Recently, Xu et al. [1] (Nat. Med. 2018;24:1246-1256) answered this question by injecting senescent cells into young mice and observing a long-lasting increase in frailty and m...
journal_title:Trends in molecular medicine
pub_type: 评论,杂志文章
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abstract::Patients who survive a stroke have an increased risk for recurrent vascular events. The mechanisms underlying the events are barely understood. A recent study suggests that stroke-enhanced atherosclerosis is induced through brain-released alarmins, which lead to systemic vascular inflammation and plaque formation. Int...
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abstract::While preclinical studies have reported improvement of behavioral deficits in the Ts65Dn mouse model of Down syndrome (DS), translation to human clinical trials to improve cognition in individuals with DS has had a poor success record. Timing of the intervention, choice of animal models, strategy for drug selection, a...
journal_title:Trends in molecular medicine
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abstract::Salmonella Typhimurium, engineered to express flagellin B, recently demonstrated unprecedented tumor control through a TLR-dependent mechanism. Here, we review new observations that support the potential of utilizing modified bacteria to enhance antitumor immunity. We also discuss the implications of these findings fo...
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abstract::Prion diseases are infectious neurodegenerative fatal disorders. There are currently no treatments or cures. Considerable evidence suggests that the infectious agent is an abnormally folded protein that promotes or seeds its normal cellular isoform to fold into the infectious form. However, the precise mechanism and f...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
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abstract::Despite concerted international efforts, mortality from neonatal infections remains unacceptably high in some areas of the world, particularly for premature infants. Recent developments in flow cytometry and next-generation sequencing technologies have led to major discoveries over the past few years, providing a more...
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journal_title:Trends in molecular medicine
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journal_title:Trends in molecular medicine
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journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
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更新日期:2002-07-01 00:00:00
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journal_title:Trends in molecular medicine
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abstract::Mutations in whirlin, a putative PDZ scaffold protein, have recently been shown to cause deafness and short cochlear hair cell stereocilia in whirler mice and recessive deafness (DFNB31) in humans. Through its PDZ domains, whirlin might organize a group of proteins into a functional complex required for stereocilia el...
journal_title:Trends in molecular medicine
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abstract::T-cell-mediated autoimmunity participates in physiological defense, maintenance and repair of the adult brain. However, unless such autoimmune responses to insults are rigorously controlled, they might lead to an autoimmune disease or other immune-related defects, where destructive activity outweighs the beneficial ef...
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abstract::Non-alcoholic steatohepatitis (NASH), a cause of cirrhosis and hepatocellular carcinoma, is characterized by fatty infiltration of the liver, inflammation, hepatocellular damage and fibrosis. Progress has been made in understanding the molecular and cellular mechanisms implicated in the pathogenesis of this condition,...
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abstract::The mTOR signaling network functions as a pivotal regulatory cascade during the development of the cerebral cortex. Aberrant hyperactivation of mTOR as a consequence of loss-of-function gene mutations encoding mTOR inhibitor proteins such as TSC1, TSC2, PTEN and STRADα has been recently linked to developmental cortica...
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abstract::The placenta is central to foetal growth and development in mammalian pregnancy. Compromised placental function (as found in pre-eclampsia) often results in life-threatening situations for both mother and foetus. The nitric-oxide (NO) signalling cascade is important for placental function, in particular for the develo...
journal_title:Trends in molecular medicine
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abstract::Cancer cells meet their needs for energy and biomass production by consuming high levels of nutrients and rewiring metabolism to support macromolecular biosynthesis. Mitochondrial enzymes play central roles in anabolic growth, and acetylation may provide a key layer of regulation over mitochondrial metabolic pathways....
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abstract::CD4(+) T cells occupy a central role in the induction and regulation of adaptive immune responses. Activated CD4(+) T helper (Th) cells exert immediate effector functions by producing cytokines and chemokines, providing help for the induction of CD8(+) cytotoxic T lymphocyte responses and memory, and providing help fo...
journal_title:Trends in molecular medicine
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abstract::Immune checkpoint inhibitors (ICIs) have revolutionised cancer immunotherapy but their success is wholly dependent on amplifying an existing immune response directed against the tumour. A recent study by Tsuchiya et al. suggests how the properties of induced pluripotent stem cells (iPSCs) may be exploited for the targ...
journal_title:Trends in molecular medicine
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abstract::During fertilization, the spermatozoon penetrates through the cumulus cells and the zona pellucida that surrounds the oocyte, before it binds and fuses with the oocyte plasma membrane to induce activation. In vitro fertilization (IVF) studies performed in non-human mammals have contributed extensive knowledge regardin...
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abstract::The programmed death 1 (PD-1) receptor and its ligands programmed death ligand 1 (PD-L1) and PD-L2, members of the CD28 and B7 families, play critical roles in T cell coinhibition and exhaustion. Overexpression of PD-L1 and PD-1 on tumor cells and tumor-infiltrating lymphocytes, respectively, correlates with poor dise...
journal_title:Trends in molecular medicine
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abstract::Innovative sequencing techniques now allow the routine access of whole genomes of pathogens, generating vast amounts of data. Phylogenetic trees are a common method for synthesizing this information. Unfortunately, these trees are often seen only as a visual support to guide researchers, thus neglecting the value of e...
journal_title:Trends in molecular medicine
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abstract::Ten percent of the population worldwide suffers from chronic kidney disease (CKD), characterized by fibrotic changes in the kidney. Fibrosis is associated with loss of epithelial parenchyma, and accumulation of myofibroblasts, fibrillary collagen, and inflammatory cells. Two recent papers highlight the critical role o...
journal_title:Trends in molecular medicine
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