Abstract:
:The major goal of epigenetic therapy is to reverse aberrant promoter hypermethylation and restore normal function of tumor suppressor genes by the use of chromatin-modifying drugs. Decitabine, or 5-aza-2'-deoxycytidine (5-aza-CdR), is a well-characterized drug that is now Food and Drug Administration approved for the treatment of myelodysplastic syndrome. Although 5-aza-CdR is an extremely potent inhibitor of DNA methylation, it is subject to degradation by hydrolytic cleavage and deamination by cytidine deaminase. We show that short oligonucleotides containing a 5-aza-CdR can also inhibit DNA methylation in cancer cells at concentrations comparable with 5-aza-CdR. Detailed studies with S110, a dinucleotide, showed that it works via a mechanism similar to that of 5-aza-CdR after incorporation of its aza-moiety into DNA. Stability of the triazine ring in aqueous solution was not improved in the S110 dinucleotide; however, deamination by cytidine deaminase was dramatically decreased. This is the first demonstration of the use of short oligonucleotides to provide effective delivery and cellular uptake of a nucleotide drug and protection from enzymatic degradation. This approach may pave the way for more stable and potent inhibitors of DNA methylation as well as provide means for improving existing therapeutics.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Yoo CB,Jeong S,Egger G,Liang G,Phiasivongsa P,Tang C,Redkar S,Jones PAdoi
10.1158/0008-5472.CAN-07-0251subject
Has Abstractpub_date
2007-07-01 00:00:00pages
6400-8issue
13eissn
0008-5472issn
1538-7445pii
67/13/6400journal_volume
67pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Rats were immunized with cultured cells from chemically induced transitional cell carcinomas of the mouse urinary bladder, and their spleen cells were hybridized with NS-1 mouse myeloma cells. Following initial screening of antibodies made by hybridoma clones, the tissue distribution of antigens defined by the antibod...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-05-01 00:00:00
abstract::Cervical cancer develops from precancerous high-grade cervical intraepithelial neoplasia (CIN) harboring a transforming infection with high-risk human papillomavirus, which is characterized by p16(INK4a) overexpression. Once such a lesion has developed, progression toward an invasive squamous cell carcinoma (SCC) may ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-2478
更新日期:2009-01-15 00:00:00
abstract::Brca2 is an important tumor suppressor associated with susceptibility to breast cancer. Although increasing evidence indicates that the primary function of Brca2 is to facilitate the repair of DNA damage via the homologous recombination pathway, how Brca2 prevents breast cancer is largely unknown. To study the role of...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-2270
更新日期:2004-03-15 00:00:00
abstract::Calmodulin contents of normal rat liver, host liver [bearing hepatoma 5123t.c.(h)], regenerating liver, and Morris hepatomas 7800, 5123t.c.(h), and 7794A were determined by phosphodiesterase assay and by radioimmunoassay. The calmodulin levels determined by both assays were significantly increased in three hepatomas w...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-07-01 00:00:00
abstract::Successful systemic gene therapy has been hindered by vector-related limitations, including toxicity and inefficient gene delivery to tumor cells after i.v. administration. To circumvent these problems, we developed a novel formulation between the polycation polyethyleneimine and DNA that mediates high-level tumor cel...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-07-15 00:00:00
abstract::Malignant undifferentiated sarcomas were induced in 11 of 15 (73.3%) newborn Syrian hamsters by s.c. inoculation of a recombinant DNA (pBK/c-rasA) containing BK virus (BKV) early region gene and the activated human c-Harvey-ras(c-Ha-ras) oncogene derived from T24 bladder carcinoma. The two genes inoculated independent...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-12-15 00:00:00
abstract::Organization of cancer cells into endothelial-like cell-lined structures to support neovascularization and to fuel solid tumors is a hallmark of progression and poor outcome. In triple-negative breast cancer (TNBC), PDGFRβ has been identified as a key player of this process and is considered a promising target for bre...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-0140
更新日期:2016-09-15 00:00:00
abstract::Receptor for advanced glycation end products (RAGE) and its ligands are overexpressed in multiple cancers. RAGE has been implicated in tumorigenesis and metastasis, but little is known of the mechanisms involved. In this study, we define a specific functional role for an alternate splice variant termed RAGE splice var...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-0595
更新日期:2010-07-01 00:00:00
abstract::Notch signaling is an area of great interest in oncology. RO4929097 is a potent and selective inhibitor of gamma-secretase, producing inhibitory activity of Notch signaling in tumor cells. The RO4929097 IC50 in cell-free and cellular assays is in the low nanomolar range with >100-fold selectivity with respect to 75 ot...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-1843
更新日期:2009-10-01 00:00:00
abstract::Eleutherobin is a novel natural product isolated from a marine soft coral that is extremely potent for inducing tubulin polymerization in vitro and is cytotoxic for cancer cells with an IC50 similar to that of paclitaxel. This compound is cross-resistant along with other multidrug-resistant agents against P-glycoprote...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-03-15 00:00:00
abstract::Alkaline phosphatase activity in human endometrial cancer cells of the estrogen-responsive Ishikawa line was markedly stimulated (3-20-fold in 4 days) by estrogens, 5 alpha-dihydrotestosterone, and dehydroepiandrosterone but not by testosterone, medroxyprogesterone acetate, glucocorticoids, several peptide hormones, p...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-06-01 00:00:00
abstract::A founder allele in the CHEK2 gene (1100delC) has been associated with an elevated risk of breast cancer. This allele is responsible for the majority of CHEK2-associated breast cancers in women from northern European countries; however, within Europe, it seems to be rare in countries that are close to the Mediterranea...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-5187
更新日期:2008-04-01 00:00:00
abstract::The effects of combined administration of cimetidine and tetragastrin on gastric acid secretion, the labeling index of the gastric mucosa, and the incidence of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in inbred Wistar rats. Prolonged administration of tetragastrin in de...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-03-15 00:00:00
abstract::Homozygous deletion of the methylthioadenosine phosphorylase (MTAP) gene is a frequent event in a wide variety of human cancers and is a possible molecular target for therapy. One potential therapeutic strategy to target MTAP-deleted tumors involves combining toxic purine analogues such as 6'-thioguanine (6TG) or 2'-f...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-0814
更新日期:2018-08-01 00:00:00
abstract::Chromosomal analysis of 16 rhabdomyosarcomas was done from four primary tumors and from 12 tumors after nude mouse passage. Seven tumors were alveolar; four of these had t(2;13)(q37;q14) and in two tumors it was the only structural abnormality. The other three alveolar tumors were near tetraploid with marker chromosom...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-02-15 00:00:00
abstract::Pleural fluid from a child previously treated for rhabdomyosarcoma produced colonies in vitro. Cells from these colonies appeared to have the light and electron microscopic appearance of rhabdomyosarcoma cells. In this case, the malignant nature of the effusion had been suspected because of the patient's previous hist...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-07-01 00:00:00
abstract::c-myc expression, amplification, and rearrangement were studied in neoplastic hepatic nodules of rats after diethylnitrosamine treatment, in hepatocellular carcinomas induced by N-methyl-N-nitrosourea, and in tumorigenic liver cell lines derived from rat hepatocytes transformed by diethylnitrosamine in vivo. Steady-st...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::Several metabolic processes, such as DNA organization and replication, transcription, and RNA processing are closely associated with the nuclear matrix. Nuclear matrix attachment regions are nucleotide sequences holding DNA tightly complexed with the nuclear scaffold and are resistant to extractions with detergents an...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
abstract::Cytoplasmic RNA was isolated from control rats or at 48 hr following carcinogen administration. A significant quantity (0.6%) of double-stranded RNA was present in control preparations, as assessed by digestion with RNase III. Following carcinogen treatment of rats, this percentage increased significantly. The results...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-08-01 00:00:00
abstract::Docetaxel tolerance and antitumor efficacy could be enhanced if drug administration was adapted to circadian rhythms. This hypothesis was investigated in seven experiments involving a total of 626 male B6D2F1 mice, synchronized with an alternation of 12 h of light and 12 h of darkness (12:12), after i.v. administratio...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
abstract::The effect of the AC33 tumor on protein synthesis in Lewis-Wistar rats was investigated under four different dietary regimens. The four diets used were: (a) 1.25 g amino acids plus 12.5 g glucose per day, (b) 1.25 g amino acids, (c) 1.25 g glucose per day, and (d) 12.5 g glucose per day. The rats were maintained on th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-11-01 00:00:00
abstract::The ability of interleukin-4 (IL-4) to mediate an antitumor response to human gliomas was studied in vivo in nude mice. To allow the effect of IL-4 to be exerted over a relatively short distance and at an optimal concentration, a transfected tumor cell line expressing a high level of IL-4 was used in mixed tumor trans...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::Four human tumor cell lines were grown in direct contact with the extracellular matrix proteins which had previously been produced by cultured rat smooth muscle cells. The extracellular matrix contained glycoproteins, elastin, and collagen, and its digestion by the tumor cells was followed by the appearance of radioac...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-09-01 00:00:00
abstract::CTLA4 is a cell surface receptor on T cells that functions as an immune checkpoint molecule to enforce tolerance to cognate antigens. Anti-CTLA4 immunotherapy is highly effective at reactivating T-cell responses against melanoma, which is postulated to be due to targeting CTLA4 on T cells. Here, we report that CTLA4 i...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-1615
更新日期:2018-01-15 00:00:00
abstract::We analyzed the gene expression profiles of clinical lung carcinomas using a cDNA microarray containing 27,648 genes or expressed sequence tags, and identified CDCA5 (cell division cycle associated 5) to be upregulated in the majority of lung cancers. Tumor tissue microarray analysis of 262 non-small cell lung cancer ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-4372
更新日期:2010-07-01 00:00:00
abstract::The pharmacokinetics of UCN-01 after administration as a 72- or 3-h infusion to cancer patients in initial Phase I trials displayed distinctive features that could not have been predicted from preclinical data. The distribution volumes (0.0796-0.158 liters/kg) and the systemic clearance (0.0407-0.252 ml/h/kg) were ext...
journal_title:Cancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::Verapamil and a number of other Ca2+ antagonists were found to potentiate DNA damage induced by 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucop yra noside (VP-16) in L1210 cells in vitro. The potentiating effect of verapamil on DNA single-strand breaks in vitro was concentration dependent, relevant to ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-08-01 00:00:00
abstract::The effect of phenobarbital (PB) pretreatment of rats on both hepatic aflatoxin B1 (AFB1)-DNA binding and AFB1-glutathione (AFB1-SG) conjugation have been examined in studies in vivo and in vitro. Male Sprague-Dawley rats fed a commercial diet with 0.1% PB in their drinking water for 1 week had total wet liver weight ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-02-15 00:00:00
abstract::The radiation response of autochthonous tumors induced by s.c. injection of 3-methylcholanthrene in ICR/JCL mice was studied. The tumors were mostly fibrosarcomas and grew with an average volume-doubling time of 2.6 days, independently of the time tumor appearance or dose of the chemical used. The tumors were locally ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-07-01 00:00:00
abstract::Calorie restriction has been shown to inhibit epithelial carcinogenesis and this method of dietary restriction reduces many circulating proteins, including insulin-like growth factor I (IGF-I). Previously, we identified a relationship between elevated tissue IGF-I levels and enhanced susceptibility to chemically induc...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-6271
更新日期:2008-05-15 00:00:00