Abstract:
:Better understanding of the underlying biology of malignant gliomas is critical for the development of early detection strategies and new therapeutics. This study aimed to define genes associated with survival. We investigated whether genes coupled with a class prediction model could be used to define subgroups of high-grade gliomas in a more objective manner than standard pathology. RNAs from 29 malignant gliomas were analysed using Agilent microarrays. We identified 21 genes whose expression was most strongly and consistently related to patient survival based on univariate proportional hazards models. In six out of 10 genes, changes in gene expression were validated by quantitative real-time PCR. After adjusting for clinical covariates based on a multivariate analysis, we finally obtained a statistical significance level for DDR1 (discoidin domain receptor family, member 1), DYRK3 (dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 3) and KSP37 (Ksp37 protein). In independent samples, it was confirmed that DDR1 protein expression was also correlated to the prognosis of glioma patients detected by immunohistochemical staining. Furthermore, we analysed the efficacy of the short interfering RNA (siRNA)-mediated inhibition of DDR1 mRNA synthesis in glioma cell lines. Cell proliferation and invasion were significantly suppressed by siRNA against DDR1. Thus, DDR1 can be a novel molecular target of therapy as well as an important predictive marker for survival in patients with glioma. Our method was effective at classifying high-grade gliomas objectively, and provided a more accurate predictor of prognosis than histological grading.
journal_name
Oncogenejournal_title
Oncogeneauthors
Yamanaka R,Arao T,Yajima N,Tsuchiya N,Homma J,Tanaka R,Sano M,Oide A,Sekijima M,Nishio Kdoi
10.1038/sj.onc.1209585subject
Has Abstractpub_date
2006-09-28 00:00:00pages
5994-6002issue
44eissn
0950-9232issn
1476-5594pii
1209585journal_volume
25pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::The 120 kD product of the c-cbl oncogene is rapidly tyrosine phosphorylated and recruited to the EGF receptor following ligand binding. Cbl's oncogenic potential is activated by a large carboxy-terminal truncation that generated v-cbl and removes the Ring finger and proline-rich SH3-binding domains. Here we show that ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201193
更新日期:1997-05-08 00:00:00
abstract::To investigate the relationship between the local configuration of a gene and its level of expression, we constructed a rat cell line, Hy5, carrying a mutant polyomavirus middle T oncogene (pmt) whose overexpression converted the cells to the transformed state. The structure of the transgene was such that pmt was able...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-03-01 00:00:00
abstract::The death mediator caspase acts as the dominant regulator during cell death induction. The CPP32 subfamily, including caspase 3 (CPP32/Yama/Apopain), is essential for the cell death signaling. We recently reported that activation of caspase 3 is regulated by complex formation with p21 or ILP. In the present study, we ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202409
更新日期:1999-02-04 00:00:00
abstract::The p21WAF1/CIP1 protein was shown to be a critical downstream effector of p53 and a potent inhibitor of cyclin-dependent kinases. We investigated the effects of exogenous p21WAF1/CIP1 in two different human breast carcinoma (HBC) cell lines MCF-7 and T47D. p21WAF1/CIP1 transfected cells formed significantly reduced n...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-11-02 00:00:00
abstract::Fanconi anemia is a hereditary cancer susceptibility disorder characterized at the cellular level by spontaneous chromosomal instability and specific hypersensitivity to DNA cross-linking agents such as mitomycin C. This phenotype suggests a possible role for the Fanconi anemia proteins in the repair of DNA lesions in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205656
更新日期:2002-07-25 00:00:00
abstract::Lung cancer is one of the major causes of cancer death and clarification of its molecular pathology is highly prioritized. The physiological importance of mRNA degradation through the CCR4-NOT deadenylase has recently been highlighted. For example, mutation in CNOT3, a gene coding for CNOT3 subunit of the CCR4-NOT com...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0603-7
更新日期:2019-04-01 00:00:00
abstract::A novel protein tyrosine kinase (PTK) substrate, p120, has been previously implicated in ligand-induced signaling through the epidermal growth factor, platelet-derived growth factor and colony-stimulating factor 1 receptors, and in cell transformation by p60v-src. We have isolated a near full-length cDNA encoding muri...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
abstract::Constitutive activation of signal transducer and activator of transcription (STAT) proteins has been detected in a wide variety of human primary tumor specimens and tumor cell lines including blood malignancies, head and neck cancer, and breast cancer. We have previously demonstrated a high frequency of Stat3 DNA-bind...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204349
更新日期:2001-05-03 00:00:00
abstract::Epigenetic regulation of gene expression is critical in the maintenance of cellular homeostasis. Dysregulation of normal epigenetic transcription occurs in abnormal physiological conditions, such as those seen in cancer cells and cells infected with parasites, making the mechanism underlying abnormal epigenetic transc...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208394
更新日期:2005-03-10 00:00:00
abstract::Ectopic expression of the intracellular domain of NOTCH-4/INT-3 leads to tumorigenesis in the mouse mammary gland. This results from a gain-of-function mutation. To evaluate gain-of-function NOTCH-4/INT-3 activity in human cancers we have surveyed human breast, lung, and colon carcinoma tissue culture cell lines for e...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203295
更新日期:2000-01-13 00:00:00
abstract::Aggrus (also known as T1alpha/podoplanin) is a membrane sialoglycoprotein whose function in tumors is unknown. We recently determined that Aggrus possessed the ability of inducing platelet aggregation and that its expression was frequently upregulated in colorectal tumors. Thus, Aggrus expression might be associated w...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207869
更新日期:2004-11-04 00:00:00
abstract::The FOXO family of Forkhead transcription factors, regulated by the phosphoinositide-3-kinase-Akt pathway, is involved in cell cycle regulation and apoptosis. Strong expression of HER2, a receptor tyrosine kinase oncogene, in cancers has been associated with a poor prognosis. Recently, FOXO4 was shown to regulate the ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208352
更新日期:2005-03-10 00:00:00
abstract::Mammalian heparanase (endo-beta-glucuronidase) degrades heparan sulfate proteoglycans and is an important modulator of the extracellular matrix and associated factors. The enzyme is preferentially expressed in neoplastic tissues and contributes to tumour metastasis and angiogenesis. To investigate the epigenetic regul...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207056
更新日期:2003-10-30 00:00:00
abstract::The Src family kinases c-Src, and its downstream effectors, the Rho family of small GTPases RhoA and Jun N-terminal kinase (JNK) have a significant role in tumorigenesis. In this report, using the Drosophila wing disc epithelium as a model system, we demonstrate that the actin-Capping Protein (CP) αβ heterodimer, whic...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.155
更新日期:2014-04-17 00:00:00
abstract::We have previously demonstrated that daunorubicin (DNR) induces apoptosis in some leukemic myeloid cell lines. We investigated a potential protective role for Bcl-2 in apoptosis induced by DNR in two leukemic cell lines, one myeloid and one lymphoid, overexpressing the anti-apoptotic gene Bcl-2. Parental cells treated...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201023
更新日期:1997-04-17 00:00:00
abstract::Adenovirus E4orf4 protein is a multifunctional viral regulator, which is involved in down regulation of virally-modulated signal transduction, in control of alternative splicing of viral mRNAs, and in induction of apoptosis in transformed cells. It has been previously shown that E4orf4 interacts with protein phosphata...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203705
更新日期:2000-08-03 00:00:00
abstract::The myb proto oncogene product (c-Myb) is a transcriptional regulator and its expression and function are tightly linked to the cellular entry into S phase and DNA synthesis. It has been shown [Venturelli, D., Travali, S. & Calabretta, B. (1990). Proc. Natl. Acad. Sci. USA, 87, 5963-5967] that inhibition of T-cell pro...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract::Previous studies have shown that the adenovirus E1A oncoprotein can bind to and inactivate the retinoblastoma tumor suppressor protein (pRb) and the transcriptional coactivators CBP/p300. In this study, wild-type E1A12S or two deletion mutants (delN, which binds pRb but not CBP/p300; delCR2, which binds to CBP/p300 bu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205050
更新日期:2002-02-07 00:00:00
abstract::The occurrence of peritoneal carcinomatosis is a major cause of treatment failure in colorectal cancer and is considered incurable. However, new therapeutic approaches have been proposed, including cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Although HIPEC has been effective ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.82
更新日期:2016-01-14 00:00:00
abstract::The intrinsic mitochondrial apoptotic pathway acts through two core pro-apoptotic proteins Bax (Bcl2-associated X protein) and Bak (Bcl2-antagonist/killer 1). Although Bax and Bak seem to have redundant roles in apoptosis, accumulating evidence also suggests that they might not be interchangeable under certain conditi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.497
更新日期:2012-06-28 00:00:00
abstract::We showed earlier that p300/CBP plays an important role in G1 progression by negatively regulating c-Myc and thereby preventing premature G1 exit. Here, we have studied the mechanism by which p300 represses c-Myc and show that in quiescent cells p300 cooperates with histone deacetylase 3 (HDAC3) to repress transcripti...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.181
更新日期:2008-09-25 00:00:00
abstract::Malignant mesotheliomas (MMs) are very aggressive tumors that respond poorly to standard chemotherapeutic approaches. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in tumor aggressiveness, in part by mediating cell survival and reducing sensitivity to chemotherapy. Using antibodies recognizi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208744
更新日期:2005-09-08 00:00:00
abstract::We have examined the possibility that the E7 proteins of the high-risk human papillomavirus (HPV) type 16 and 18 and the oncogenic adenovirus (Ad) type 12 E1A protein share the ability to down-regulate the expression of components of the antigen processing and presentation pathway, as a common strategy in the evasion ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203860
更新日期:2000-10-05 00:00:00
abstract::Poor-prognosis oestrogen receptor-positive breast cancer is characterised by the presence of high-level focal amplifications. We utilised a focused small interfering RNA screen in 14 breast cancer cell lines to define genes that were pathogenic in three genomic regions focally amplified in oestrogen receptor-positive ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.202
更新日期:2014-05-08 00:00:00
abstract::The transcription factor PU.1 is essential for terminal myeloid differentiation, B- and T-cell development, erythropoiesis and hematopoietic stem cell maintenance. PU.1 functions as oncogene in Friend virus-induced erythroleukemia and as tumor suppressor in acute myeloid leukemias. Moreover, Friend virus-induced eryth...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1211004
更新日期:2008-05-29 00:00:00
abstract::Hedgehog pathway activity has been demonstrated in malignant glioma. However, its role in tumor growth has not been determined. Here we demonstrate that pharmacological inhibition of the Hedgehog pathway in established orthotopic malignant glioma xenografts confers a survival advantage. Pathway inhibition is measured ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.208
更新日期:2009-10-01 00:00:00
abstract::Leukemogenesis requires two classes of mutations, one that promotes proliferation and one that blocks differentiation. The erythroleukemia induced by Friend virus is a multistage disease characterized by an early proliferative stage driven by the interaction of the viral glycoprotein, gp55, with Sf-Stk and the EpoR, a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.202
更新日期:2009-09-24 00:00:00
abstract::Pharmacological inactivation of cancer genes or products is being used as a strategy for therapy in oncology. To investigate the potential role of BCR-ABLp190 cessation in leukaemia development, we generated mice carrying a tetracycline-repressible BCR-ABLp190 transgene. These mice were morphologically normal at birth...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209968
更新日期:2007-03-15 00:00:00
abstract::Ferritin is the major intracellular iron storage protein that sequesters excess free iron to minimize generation of iron-catalysed reactive oxygen species. We previously demonstrated that expression of ferritin heavy chain (ferritin H) was induced by pro-oxidants, which is a part of cellular antioxidant response to pr...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208901
更新日期:2005-11-17 00:00:00
abstract::Oxygen is the ultimate source of oxidizing power for disulfide bond formation, suggesting that under limiting oxygen proper protein folding might be compromised. We show that secretion of vascular endothelial growth factor (VEGF), a protein with multiple disulfide bonds, was indeed impeded under hypoxia and was partia...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208325
更新日期:2005-02-03 00:00:00