Abstract:
:Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-scale segmental abnormalities involving other chromosomes, but the reasons for this association are unknown. We find that large-scale chromosomal alterations accumulate during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with NF2 on chromosome 22q in a majority of aggressive meningiomas. In addition, tumor-specific splicing of CHEK2 in meningioma leads to decreased functional Chk2 protein expression. We show that enforced Chk2 knockdown in meningioma cells decreases DNA repair. Furthermore, Chk2 depletion increases centrosome amplification, thereby promoting chromosomal instability. Taken together, these data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas.
journal_name
Neoplasiajournal_title
Neoplasia (New York, N.Y.)authors
Yang HW,Kim TM,Song SS,Shrinath N,Park R,Kalamarides M,Park PJ,Black PM,Carroll RS,Johnson MDdoi
10.1593/neo.111574subject
Has Abstractpub_date
2012-01-01 00:00:00pages
20-8issue
1eissn
1522-8002issn
1476-5586journal_volume
14pub_type
杂志文章相关文献
NEOPLASIA文献大全abstract::The long noncoding (lnc) RNA H19 was involved in the tumorigenesis of many types of cancer. However, the role of H19 in the tumorigenesis of colon cancer has not been fully illustrated. Recent studies suggested a potential relationship between H19 and vitamin D receptor (VDR) signaling. Considering the pivotal role of...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2016.10.007
更新日期:2017-03-01 00:00:00
abstract::In this study, a new compound, 4-(N)-docosahexaenoyl 2', 2'-difluorodeoxycytidine (DHA-dFdC), was synthesized and characterized. Its antitumor activity was evaluated in cell culture and in mouse models of pancreatic cancer. DHA-dFdC is a poorly soluble, pale yellow waxy solid, with a molecular mass of 573.3Da and a me...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2015.11.012
更新日期:2016-01-01 00:00:00
abstract::In ovarian cancer, loss of BRCA gene expression in tumors is associated with improved response to chemotherapy and increased survival. A means to pharmacologically downregulate BRCA gene expression could improve the outcomes of patients with BRCA wild-type tumors. We report that vascular endothelial growth factor rece...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2014.04.003
更新日期:2014-04-01 00:00:00
abstract::Polyploidy contributes to extensive intratumor genomic heterogeneity that characterizes advanced malignancies and is thought to limit the efficiency of current cancer therapies. It has been shown that telomere deprotection in p53-deficient mouse embryonic fibroblasts leads to high rates of polyploidization. We now sho...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.121398
更新日期:2013-02-01 00:00:00
abstract::The transforming growth factorbeta (TGFbeta) superfamily regulates a broad spectrum of biological responses throughout embryonic development and adult life, including cell proliferation and differentiation, epithelial-to-mesenchymal transition, apoptosis, and angiogenesis. TGFbeta members initiate signaling by bringin...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章,评审
doi:10.1593/neo.06472
更新日期:2006-08-01 00:00:00
abstract::Somatic PIK3CA mutations are often present in colorectal cancer. Mutant PIK3CA activates AKT signaling, which up-regulates fatty acid synthase (FASN). Microsatellite instability (MSI) and CpG island methylator phenotype (CIMP) are important molecular classifiers in colorectal cancer. However, the relationship between ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.08336
更新日期:2008-06-01 00:00:00
abstract::Survival in high-risk neuroblastoma (HR-NB) patients remains poor despite multimodal treatment. We aimed to identify HR-NB patients with worse outcomes by analyzing the genomic instability derived from segmental chromosomal aberrations. We calculated 3 genomic instability indexes for primary tumor SNP array profiles f...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2020.11.001
更新日期:2021-01-01 00:00:00
abstract::We have demonstrated that modifying the tumor microenvironment through intratumoral administration of adenoviral vectors (Ad) encoding the conditional cytotoxic molecule, i.e., HSV1-TK and the immune-stimulatory cytokine, i.e., fms-like tyrosine kinase 3 ligand (Flt3L) leads to T-cell-dependent tumor regression in rod...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.11024
更新日期:2011-10-01 00:00:00
abstract::Increases in the levels and/or activity of nonreceptor tyrosine kinases c-Src and c-Yes are often associated with colorectal carcinogenesis. The physiological consequences of increased c-Yes activity during the early and late stages of tumorigenesis, in addition to the degree of redundancy between c-Yes and c-Src in c...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.07442
更新日期:2007-09-01 00:00:00
abstract::It has been proposed that the structural and numerical chromosome abnormalities recorded in breast cancer could be the result of telomere dysfunction and that telomerase is activated de novo to provide a survival mechanism curtailing further chromosomal aberrations. However, recent in vivo and in vitro data show that ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/s1476-5586(03)80009-x
更新日期:2003-03-01 00:00:00
abstract::The high prevalence and long latency period of prostate cancer (PCa) provide a unique opportunity to control disease progression with dietary and nutraceutical approaches. We developed ProFine, a standardized composition of luteolin, quercetin, and kaempferol, and investigated its potential as a nutraceutical for PCa ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2018.06.003
更新日期:2018-08-01 00:00:00
abstract::This white paper discusses prospects for advancing hyperpolarization technology to better understand cancer metabolism, identify current obstacles to HP (hyperpolarized) 13C magnetic resonance imaging's (MRI's) widespread clinical use, and provide recommendations for overcoming them. Since the publication of the first...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章,评审
doi:10.1016/j.neo.2018.09.006
更新日期:2019-01-01 00:00:00
abstract::High microvascular density (MVD) in the primary tumor has been shown to be associated with increased incidence of lymph node metastases and poor clinical outcome. Other investigations have revealed that a large fraction of hypoxic tissue in the primary tumor is associated with metastatic disease and impaired survival....
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2014.07.003
更新日期:2014-07-01 00:00:00
abstract::Epstein-Barr virus (EBV) latent infection is a critical event in nasopharyngeal carcinoma (NPC) tumorigenesis. EBV-encoded genes have been shown to be involved in immune evasion and in the regulation of various cellular signaling cascades. To elucidate the roles of EBV in NPC development, stable infection of EBV in na...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.05625
更新日期:2006-03-01 00:00:00
abstract::Tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein (TRADD) is an important adaptor in TNFR1 signaling and has an essential role in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and survival signaling. Increased expression of TRADD is sufficient to activate NF-κ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.13608
更新日期:2013-08-01 00:00:00
abstract::Pediatric rhabdomyosarcoma (RMS) is a morphologically and genetically heterogeneous malignancy commonly classified into three histologic subtypes, namely, alveolar, embryonal, and anaplastic. An issue that continues to challenge effective RMS patient prognosis is the dearth of molecular markers predictive of disease s...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.13286
更新日期:2013-09-01 00:00:00
abstract::Pancreatic carcinoma has an extremely bad prognosis due to lack of early diagnostic markers and lack of effective therapeutic strategies. Recently, we have established an in vitro model recapitulating the first steps in the carcinogenesis of the pancreas. SV40 large T antigen-immortalized bovine pancreatic duct cells ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.06754
更新日期:2007-02-01 00:00:00
abstract::The MEK-ERK growth signaling pathway is important in human hepatocellular carcinoma (HCC). To evaluate the targeting of this pathway in HCC, we characterized a novel, orally-active MEK inhibitor, PD184161, using human HCC cells (HepG2, Hep3B, PLC, and SKHep) and in vivo human tumor xenografts. PD184161 inhibited MEK a...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.05373
更新日期:2006-01-01 00:00:00
abstract::Even with increasing evidence for roles of glycolytic enzymes in controlling cancerous characteristics, the best target of candidate metabolic enzymes for lessening malignancy remains under debate. Pyruvate is a main glycolytic metabolite that could be mainly converted into either lactate by Lactate Dehydrogenase A (L...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2019.04.007
更新日期:2019-07-01 00:00:00
abstract::Several studies have linked vascular density, identified in histologic sections, to "metastatic risk." Functional information of the vasculature, not readily available from histologic sections, can be obtained with contrast-enhanced MRI to exploit for therapy or metastasis prevention. Our aims were to determine if hum...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900129
更新日期:2001-03-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is an intrinsically chemotherapy refractory malignancy. Development of effective therapeutic regimens would be facilitated by improved preclinical HCC models. Currently, most models consist of subcutaneous human tumor transplants in immunodeficient mice; however, these do not reproduce t...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.91872
更新日期:2010-03-01 00:00:00
abstract::SEMA3F is a secreted semaphorin with potent antitumor activity, which is frequently downregulated in lung cancer. In cancer cell lines, SEMA3F overexpression decreases hypoxia-induced factor 1alpha protein and vascular endothelial growth factor mRNA, and inhibits multiple signaling components. Therefore, understanding...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.81074
更新日期:2009-02-01 00:00:00
abstract::Pancreatic invasive ductal adenocarcinoma (PDAC) is a representative intractable malignancy under the current cancer therapies, and is considered a scirrhous carcinoma because it develops dense stroma. Both PODXL1, a member of CD34 family molecules, and C5aR, a critical cell motility inducer, have gained recent attent...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2019.09.003
更新日期:2019-12-01 00:00:00
abstract::c-Cbl, a RING-type ubiquitin E3 ligase, downregulates various receptor tyrosine kinases (e.g., epidermal growth factor receptor (EGFR)), leading to inhibition of cell proliferation. Moreover, patients with myeloid neoplasm frequently harbor c-Cbl mutations, implicating the role of c-Cbl as a tumor suppressor. Recently...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2015.06.003
更新日期:2015-06-01 00:00:00
abstract::The benefits of inhibiting vascular endothelial growth factor (VEGF) signaling in cancer patients are predominantly attributed to effects on tumor endothelial cells. Targeting non-endothelial stromal cells to further impact tumor cell growth and survival is being pursued through the inhibition of additional growth fac...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.101162
更新日期:2011-01-01 00:00:00
abstract::We report herein a method to track the migration of dendritic cells (DCs) using optical imaging. With the assistance of the delivery module, fluorescein isothiocyanate (FITC) could internalize inside DCs within 15 minutes of incubation. The fluorescent signal was mostly cytoplasmic and could be detected using in vivo ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.07586
更新日期:2007-12-01 00:00:00
abstract::Soluble CD44 proteins generated by proteolytic cleavage or aberrant intron retention have been shown to antagonize the ligand binding activity of the corresponding cell surface receptor, inducing apoptosis and inhibiting tumor growth. Interestingly, such findings appear to contradict recent studies demonstrating a cor...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900045
更新日期:1999-11-01 00:00:00
abstract::The most frequent site of metastasis in human prostate cancer (PCa) is the bone. Preferential adhesion of PCa cells to bone-specific factors may facilitate the selective metastasis of the skeleton. The most abundant protein within the skeleton is type I collagen. We previously demonstrated that PCa cells selected in v...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.08380
更新日期:2008-08-01 00:00:00
abstract::The Wilms tumor gene (WT1) is mutated or deleted in patients with heredofamilial syndromes associated with the development of Wilms tumors, but is infrequently mutated in sporadic Wilms tumors. By comparing the microarray profiles of syndromic versus sporadic Wilms tumors and WT1-inducible Saos-2 osteosarcoma cells, w...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.07869
更新日期:2008-01-01 00:00:00
abstract::PX-478 is a new agent known to inhibit the hypoxia-responsive transcription factor, HIF-1alpha, in experimental tumors. The current study was undertaken in preparation for clinical trials to determine which noninvasive imaging endpoint(s) is sensitive to this drug's actions. Dynamic contrast-enhanced (DCE) and diffusi...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.04628
更新日期:2005-05-01 00:00:00