Abstract：
:Ewing sarcoma is a rare but aggressive disease most common in young adults. This cancer is driven by a unique chimeric fusion oncogene but targeted strategies have been elusive. Here we report the identification of the protein kinase PKC-ß (PRKCB) as a disease-specific druggable target for treatment of Ewing sarcoma. We found that transcriptional activation of PRKCB was directly regulated by the chimeric fusion oncogene EWSR1-FLI1 that drives this cancer. PRKCB phosphorylated histone H3T6 to permit global maintenance of H3K4 trimethylation at a variety of gene promoters. PRKCB loss induced apoptosis in vitro and prevented tumor growth in vivo. Gene expression profiling revealed a strong overlap between genes modulated by EWSR1-FLI1 and PRKCB in regulating crucial signaling pathways. Taken together, our findings offer a preclinical proof-of-concept for PRKCB as a promising therapeutic target in Ewing sarcoma.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Surdez D,Benetkiewicz M,Perrin V,Han ZY,Pierron G,Ballet S,Lamoureux F,Rédini F,Decouvelaere AV,Daudigeos-Dubus E,Geoerger B,de Pinieux G,Delattre O,Tirode Fdoi
10.1158/0008-5472.CAN-12-0371subject
Has Abstractpub_date
2012-09-01 00:00:00pages
4494-503issue
17eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-0371journal_volume
72pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:The role of CD4+ T lymphocytes in antitumor immunity has been largely attributed to providing signals required for the priming of MHC class I-restricted CD8+ cytotoxic T lymphocytes, and CD8+ cytotoxic T lymphocytes are thought to serve as the predominant mediators of tumor killing in vivo. We decided to evaluate the ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-03-01 00:00:00
abstract：:The current study is a continuation of our previous work showing that bone marrow activated in interleukin 2 has antitumor and antiviral activity in vitro. The antitumor efficacy of IL-2-activated bone marrow cells in vivo was assessed here. Our results indicated that bone marrow cells activated in IL-2 for 3 days (AB...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
abstract：:Preexisting and acquired resistance to epidermal growth factor receptor (EGFR) inhibitors limits their clinical usefulness in patients with advanced non-small cell lung cancer (NSCLC). This study characterizes the efficacy and mechanisms of the combination of gefitinib or erlotinib with OSU-03012, a celecoxib-derived ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-1336
更新日期：2008-04-15 00:00:00
abstract：:The effects of the triparanol analogues chlorotrianisene, clomiphene, tamoxifen, 5-[p-(fluoren-9-ylidenemethyl)phenyl]-2-piperidineethanol (MDL 10393), MDL 8917v, nafoxidine, 2-[p-(6-methoxy-2-phenylinden-3-yl)phenoxy]triethylamine (U-11555A), 2-[p-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]triethylamine (U-10...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-10-01 00:00:00
abstract：:During 2007, approximately 200,000 people in the United States will be diagnosed with brain tumors. Gliomas account for 77% of primary malignant brain tumors, and the prognosis has hardly changed in the past 20 years, with only 30% of patients with malignant glioma surviving 5 years after diagnosis. Oncolytic adenovir...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-4675
更新日期：2007-09-01 00:00:00
abstract：:Prostate cancer is the most common cancer in men. Advanced prostate cancer spreading beyond the gland is incurable. Identifying factors that regulate the spread of tumor into the regional nodes and distant sites would guide the development of novel diagnostic, prognostic, and therapeutic targets. The aim of our study ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-2667
更新日期：2005-06-01 00:00:00
abstract：:Metabolic reprogramming is a hallmark of cancer that includes increased glucose uptake and accelerated aerobic glycolysis. This phenotype is required to fulfill anabolic demands associated with aberrant cell proliferation and is often mediated by oncogenic drivers such as activated BRAF. In this study, we show that th...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-2215
更新日期：2018-05-01 00:00:00
abstract：:The incidence, distribution, size, and histopathology of colonic tumors induced by parenteral administration of 1,2-dimethylhydrazine were examined in rats fed a chemically defined fiber-free diet or nutritionally and calorically equivalent diets containing either 4.5 or 9.0% purified cellulose or pectin. This double-...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-08-01 00:00:00
abstract：:This study investigates possible alterations in exons 5 through 8 of the p53 gene and altered p53 protein expression in the Syrian golden hamster model of pancreatic ductal adenocarcinoma. In the Syrian hamster p53 sequence, 1469 base pairs are presented for the genomic regions surrounding exons 5 through 8, along wit...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-07-15 00:00:00
abstract：:Malignant pleural mesothelioma is a relatively uncommon and yet incurable tumor. The pathogenesis of mesothelioma remains poorly understood. This study evaluated the role of Wnt signaling in mesothelioma. Western blot analysis was conducted to confirm the expression of Dishevelled (Dvl) and cytosolic beta-catenin in m...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-08-01 00:00:00
abstract：:The human urinary bladder carcinogen, 4-aminobiphenyl (ABP), is known to undergo hepatic metabolism to an N-hydroxy arylamine and its corresponding N-glucuronide. It has been proposed that these metabolites are both transported through the blood via renal filtration to the urinary bladder lumen where acidic pH can fac...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-08-15 00:00:00
abstract：:(E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC) is known as an inhibitor of ribonucleoside diphosphate reductase, a key enzyme in the de novo pathway of DNA synthesis. FMdC was tested as a modifier of radiation response in vitro on a human colon carcinoma cell line (WiDr), and the observed radiosensitization was confirm...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-10-15 00:00:00
abstract：:Non-P-glycoprotein multidrug resistance of HL60/ADR cells appears to be related to overexpression of the MRP gene. Recent studies suggest that this gene may play an important role in a new form of cell resistance to certain chemotherapeutic agents. To examine mechanisms regulating transcriptional activity of this gene...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-08-15 00:00:00
abstract：:Noninvasive imaging techniques to image and characterize delivery and transport of macromolecules through the extracellular matrix (ECM) and supporting stroma of a tumor are necessary to develop treatments that alter the porosity and integrity of the ECM for improved delivery of therapeutic agents and to understand fa...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-3682
更新日期：2005-02-15 00:00:00
abstract：:Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the Text Information Extraction System (TIES) Cancer...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-15-1973
更新日期：2015-12-15 00:00:00
abstract：:Overexpression of the polycomb group protein enhancer of zeste homologue 2 (EZH2) occurs in diverse malignancies, including prostate cancer, breast cancer, and glioblastoma multiforme (GBM). Based on its ability to modulate transcription of key genes implicated in cell cycle control, DNA repair, and cell differentiati...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-1622
更新日期：2009-12-15 00:00:00
abstract：:In meningeal carcinomatosis, retroviral vector-producer cells can be introduced into the thecal sac and circulate in the cerebrospinal fluid to reach malignant tumor cells in the leptomeninges, release vector particles, and selectively infect and transfer a gene of interest to these cells. Gene transfer experiments wi...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-04-15 00:00:00
abstract：:The effects of an altered content of dietary iodine and fat on the development of N-nitrosomethylurea-induced mammary tumors in rats were studied and correlated with thyroid and pituitary function studies. In three separate experiments, animals fed a semisynthetic diet containing 11.8% fat had an earlier time of tumor...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-03-01 00:00:00
abstract：:The c-Fes protein-tyrosine kinase exhibits strong expression in myeloid hematopoietic cells. Previous studies have shown that Fes induces differentiation in the chronic myelogenous leukemia-derived cell line K-562, suggesting that the Fes signal for differentiation is dominant to the Bcr-Abl signal for transformation ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-02-15 00:00:00
abstract：:The lymphoid tissue in the omentum, at the so-called milky spots, is known as an initial place for disseminated cancer cells to develop into solid tumors. In the present study, i.p. macrophages significantly took up oligomannose-coated liposomes (OMLs) that were injected into the peritoneal cavity, and then gradually ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-0470
更新日期：2006-09-01 00:00:00
abstract：:Peroxisome proliferators (PPs) act as nongenotoxic tumor promoters in rodents. Their hepatocarcinogenicity requires the presence of the PP-activated receptor alpha (PPARalpha); however, the exact role played by this transcription factor in the liver, more precisely in liver cell growth and differentiation, is not know...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-02-01 00:00:00
abstract：:The intention of this study was to estimate the pharmacological advantage of a clinically applicable method of isolated liver perfusion (ILP) over hepatic artery infusion (HAI) administering various doses of 5-fluorouracil (FUra). FUra concentrations were measured using high-performance liquid chromatography in liver ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-03-15 00:00:00
abstract：:All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promote oncogenesis when they are mutationally activated at codon 12, 13, or 61. Although there is a high degree of similarity among the isoforms, K-Ras mutations are far more frequently observed in cancer, and each isofor...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-2612
更新日期：2012-05-15 00:00:00
abstract：:In order to improve local control of tumors over that achievable with local hyperthermia and radiation, we are testing the use of systemic cis-diamminedichloroplatinum(II) (CDDP) in conjunction with the other two modalities. In the FSaIIC fibrosarcoma, growth delay experiments indicated that the use of any two modalit...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-05-15 00:00:00
abstract：:Human recombinant interleukin 1 alpha (IL-1 alpha) and IL-1 beta inhibited the replication of the mammary tumor cell line, MDA-MB-415; stimulated division in the colon carcinoma, SW-48; and had no effect on the growth of the milk mammary line, HBL-100. Inhibition of growth was reflected in a significant decrease in DN...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) accumulates in the nucleus in aggressive transitional cell carcinoma (TCC) cells and this histologic feature is a marker of poor prognosis in human bladder cancer tissues. Here we report that HB-EGF can be exported from the nucleus during stimul...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-0942
更新日期：2005-09-15 00:00:00
abstract：:Increasing the expression of c-FMS (colony-stimulating factor 1 receptor) by introduction of a transgene reduced the concentration of retinoic acid or 1,25-dihydroxy vitamin D3 needed to cause myeloid or monocytic cell differentiation and hypophosphorylation of the retinoblastoma tumor suppressor protein (RB) typicall...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-05-15 00:00:00
abstract：:Capsaicin (N-vanillyl-8-methyl-1-nonenamide) is a homovanillic acid derivative found in pungent fruits. Several investigators have reported the ability of capsaicin to inhibit events associated with the promotion of cancer. However, the effects of capsaicin on human leukemic cells have never been investigated. We inve...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.can-03-1670
更新日期：2004-02-01 00:00:00
abstract：:Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer and is phenotypically distinct from other forms of locally advanced breast cancer. In a previous study, we identified specific genetic alterations of IBC that could account for a highly invasive phenotype. RhoC GTPase was overexpressed in 90...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-10-15 00:00:00
abstract：:Delivery of therapeutic agents to the brain and its neoplasms depends on the presence of membrane transport proteins in the blood-brain barrier and in the target cells. The cellular and subcellular localization of these membrane transporters determines the drug accessibility to the brain and its tumors. We therefore a...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-1271
更新日期：2005-12-15 00:00:00
