Abstract:
:The Nup98-HoxD13 (NHD13) fusion gene was identified in a patient with therapy-related myelodysplastic syndrome (MDS). When transgenically expressed in hematopoietic cells, mice faithfully recapitulate human disease with serial progression from peripheral blood (PB) cytopenias and increased bone marrow (BM) blasts to acute leukemia. It is well accepted that genomic instability in dysplastic hematopoietic stem/progenitor cells (HSPC) drives the evolution of MDS to acute leukemia. Findings here demonstrate that reticulocytes, myeloid and lymphoid PB cells of NHD13 mice, display an increase in the age-associated loss of glycosylphosphatidylinositol-linked surface proteins versus wild type controls. These data correlate with a progressive increase in the DNA damage response as measured by γ-H2AX activity, accumulating BM blasts as the disease progresses and finally development of acute leukemia. These findings clearly demonstrate a state of progressive genomic instability that increases the likelihood of a "second hit" or complimentary mutation later in the disease to trigger development of acute leukemia and underscores the mechanistic nature of how the NUP98-HoxD13 transgene induces progression of MDS to acute leukemia. Additionally, these data support the use of the PIG-A assay as an efficient, real-time surrogate marker of the genomic instability that occurs in the MDS HSPCs. Key Point The PIG-A assay is a sensitive, nonlethal method for the serial assessment of genomic instability in mouse models of MDS.
journal_name
Neoplasiajournal_title
Neoplasia (New York, N.Y.)authors
Byrne M,Bennett RL,Cheng X,May WSdoi
10.1016/j.neo.2014.07.004subject
Has Abstractpub_date
2014-08-01 00:00:00pages
627-33issue
8eissn
1522-8002issn
1476-5586pii
S1476-5586(14)00091-8journal_volume
16pub_type
杂志文章相关文献
NEOPLASIA文献大全abstract::Although medulloblastoma is the most common pediatric malignant brain tumor, its molecular underpinnings are largely unknown. We have identified rare, recurrent homozygous deletions of Kruppel-like Factor 4 (KLF4) in medulloblastoma using high-resolution single nucleotide polymorphism arrays, digital karyotyping, and ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.91122
更新日期:2010-01-01 00:00:00
abstract::Aberrant signaling through the AKT kinase mediates oncogenic phenotypes including cell proliferation, survival, and therapeutic resistance. Here, we utilize a bioluminescence reporter for AKT kinase activity (BAR) to noninvasively assess the therapeutic efficacy of the EGFR inhibitor erlotinib in KRAS-mutated lung can...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2017.02.005
更新日期:2017-04-01 00:00:00
abstract::Abnormal architecture of the tumor blood network, as well as heterogeneous erythrocyte flow, leads to temporal fluctuations in tissue oxygen tension exposing tumor and stromal cells to cycling hypoxia. Inflammation is another feature of tumor microenvironment and is considered as a new enabling characteristic of tumor...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2014.11.003
更新日期:2015-01-01 00:00:00
abstract::Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2019.09.001
更新日期:2020-01-01 00:00:00
abstract::Although it is well known that nasopharyngeal carcinoma (NPC) is closely related with Epstein-Barr virus (EBV), few data are available about which and how EBV-expressed gene is involved in the carcinogenesis of human nasopharyngeal epithelial cells. EBV-encoded BARF1 (BamH I-A right frame 1) gene has been shown to be ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.09706
更新日期:2009-09-01 00:00:00
abstract::Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glu...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2017.02.009
更新日期:2017-04-01 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
abstract::Our recent studies have shown that annexin II, expressed on the cell surface of osteoblasts, plays an important role in the adhesion of hematopoietic stem cells (HSCs) to the endosteal niche. Similarly, prostate cancer (PCa) cells express the annexin II receptor and seem to use the stem cell niche for homing to the bo...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.91384
更新日期:2010-02-01 00:00:00
abstract::The maspin gene is not expressed in normal human pancreas, but its expression is acquired during human pancreatic carcinogenesis. In other normal human cells and their malignant counterparts, maspin expression is controlled through the epigenetic state of its promoter. In studies presented herein, we used bisulfite ge...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/s1476-5586(03)80045-3
更新日期:2003-09-01 00:00:00
abstract::It is widely accepted that a deranged immune system plays a key role in the onset and evolution of classic Kaposi sarcoma (CKS). Nevertheless, the usage of the T-cell receptor (TCR) β-variable (BV) chain repertoire expressed by peripheral blood lymphocytes in patients with CKS is still unknown. With the aim of providi...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1596/neo.11646
更新日期:2012-06-01 00:00:00
abstract::Tumor necrosis factor (TNF) has been implicated in inflammation-associated tumor progression. Although multiple reports identified a role for TNF signaling in established cancers, few studies have assessed the impact of TNF blockade on early tumor formation promotion. We aimed at exploring the effects of TNF neutraliz...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.111224
更新日期:2011-12-01 00:00:00
abstract::There have been no reports describing the effects of cancer cell-derived extracellular vesicles (EVs) on three-dimensional organoids. In this study, we delineated the proneoplastic effects of esophageal adenocarcinoma (EAC)-derived EVs on gastric organoids (gastroids) and elucidated molecular mechanisms underlying the...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2017.06.007
更新日期:2017-11-01 00:00:00
abstract::Glioblastoma in adults, and medulloblastoma and pineoblastoma that mainly affect children, are aggressive brain tumors. The survival for patients with glioblastoma remains dismal. While the cure rate for medulloblastoma exceeds 70%, this figure has stagnated over the past few decades and survivors still contend with s...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2018.02.004
更新日期:2018-05-01 00:00:00
abstract::The bcl-2 and c-myc oncogenes cooperate to transform multiple cell types. In the pediatric malignancy NB(2), Bcl-2 is highly expressed. In tumors with a poor prognosis, N-Myc, a protein homologous to c-Myc, is overexpressed as a result of gene amplification. The present study was designed to determine whether Bcl-2 co...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900171
更新日期:2001-07-01 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::In spite of intensive and increasingly successful attempts to determine the multiple steps involved in colorectal carcinogenesis, the mechanisms responsible for metastasis of colorectal tumors to the liver remain to be clarified. To identify genes that are candidates for involvement in the metastatic process, we analy...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900185
更新日期:2001-09-01 00:00:00
abstract::Research efforts in the area of palaeopathology have been seen as an avenue to improve our understanding of the pathogenesis of cancer. Answers to questions of whether dinosaurs had cancer, or if cancer plagued ancient civilizations, have captured the imagination as well as the popular media. Evidence for dinosaurian ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 历史文章,杂志文章
doi:10.1593/neo.101588
更新日期:2010-12-01 00:00:00
abstract::A theoretical model for the intraperitoneal (i.p.) delivery of cisplatin and heat to tumor metastases in tissues adjacent to the peritoneal cavity is presented. The penetration distance (the depth to which drug diffuses directly from the cavity into tissues) is predicted to be on the order of 0.5 mm. The model shows t...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.03205
更新日期:2004-03-01 00:00:00
abstract::Two genetically engineered, conditional mouse models of lung tumor formation, K-ras(LSL-G12D) and K-ras(LSL-G12D)/p53(LSL-R270H), are commonly used to model human lung cancer. Developed by Tyler Jacks and colleagues, these models have been invaluable to study in vivo lung cancer initiation and progression in a genetic...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.81030
更新日期:2009-01-01 00:00:00
abstract::Approximately 50% of prostate cancers harbor the TMPRSS2:ERG fusion, resulting in elevated expression of the ERG transcription factor. Despite the identification of this subclass of prostate cancers, no personalized therapeutic strategies have achieved clinical implementation. Kinases are attractive therapeutic target...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2019.02.005
更新日期:2019-04-01 00:00:00
abstract::Hu-antigen R (HuR) is an RNA-binding posttranscriptional regulator that belongs to the Hu/ELAV family. HuR expression levels are modulated by a variety of proteins, microRNAs, chemical compounds, or the microenvironment, and in turn, HuR affects mRNA stability and translation of various genes implicated in breast canc...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章,评审
doi:10.1016/j.neo.2016.09.002
更新日期:2016-11-01 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::In order to find common genetic abnormalities that may identify loci of genes involved in the development of adenoid cystic carcinoma (ACC), we investigated DNA copy number changes in 24 of these tumors by comparative genomic hybridization (CGH). Our results indicate that unlike many carcinomas, ACCs have relatively f...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900158
更新日期:2001-05-01 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::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::BUB1 (budding uninhibited by benzimidazoles-1) is required for efficient TGF-β signaling, through its role in stabilizing the TGFBR1 and TGFBR2 complex. Here we demonstrate that TGFBR2 phosphorylates BUB1 at Serine-318, which is conserved in primates. S318 phosphorylation abrogates the interaction of BUB1 with TGFBR1 ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2020.02.001
更新日期:2020-04-01 00:00:00
abstract::The biologic plausibility of an association between type 2 diabetes mellitus (T2D) and lung cancer has received increasing attention, but the results of investigations remain largely inconclusive. In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic effects of EGFR ta...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2017.02.011
更新日期:2017-05-01 00:00:00
abstract::T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy originating from T-cell precursors. The genetic landscape of T-ALL has been largely characterized by next-generation sequencing. Yet, the transcriptome of miRNAs (miRNome) of T-ALL has been less extensively studied. Using small RNA sequencing, we ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2019.01.004
更新日期:2019-03-01 00:00:00
abstract::Gastrin-releasing peptide receptor (GRPR) and the epidermal growth factor receptor (EGFR) are expressed in several cancers including non-small cell lung cancer (NSCLC). Here we demonstrate the activation of EGFR by the GRPR ligand, gastrin-releasing peptide (GRP), in NSCLC cells. GRP induced rapid activation of p44/42...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.04454
更新日期:2005-04-01 00:00:00
abstract::Antagonists of growth hormone-releasing hormone(GH-RH)inhibit the growth of various cancers by mechanisms that involve the suppression of the insulin-like growth factor (IGF)-I and/or IGF-II. In view of the importance of the IGF system in glioma tumorigenesis, the effects of GH-RH antagonists MZ-5-156 and JV-1-36 were...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900074
更新日期:2000-05-01 00:00:00