Abstract:
:Polyglutamyl derivatives of methotrexate (MTX) and 10-deazaaminopterin (10-DAM) containing a total of one through six glutamate residues (Glu residues) were tested as inhibitors of dihydrofolate reductase (DHFR) derived from sheep, chicken, and beef liver. The ability of dihydropteroylpentaglutamate to antagonize the inhibitory activity of these analogues was also studied. The most striking effects were seen with sheep liver DHFR, where polyglutamylation of MTX causes stepwise decreases in the concentration required for 50% inhibition (IC50) with each additional Glu residue until MTX with a total of six Glu residues has an IC50 value 1/3 that of MTX. With 10-DAM the pattern is more complex. The IC50 values increase with addition of Glu residues until a maximum is reached with 10-DAM having a total of three Glu residues which has a value twice that of 10-DAM. 10-DAM with a total of four Glu residues and 10-DAM with a total of five Glu residues have progressively lower IC50 values, the latter being equipotent with 10-DAM. With dihydropteroylpentaglutamate as substrate instead of dihydrofolate, the IC50 values are increased 2- to 5-fold for both MTX and 10-DAM derivatives. The results obtained with chicken liver and beef liver DHFR are generally similar to those described for the sheep liver enzyme, but the effects of polyglutamylation are less pronounced. The addition of 0.2 M KCl to the assay system reduces the differences in inhibitory potency of the polyglutamyl derivatives with all three enzymes tested. We conclude that polyglutamylation can alter the interaction of folate analogues and dihydrofolate with DHFR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Kumar P,Kisliuk RL,Gaumont Y,Nair MG,Baugh CM,Kaufman BTsubject
Has Abstractpub_date
1986-10-01 00:00:00pages
5020-3issue
10eissn
0008-5472issn
1538-7445journal_volume
46pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Some clinical studies suggest that timing of surgery during specific menstrual phases may influence the chances of survival for premenopausal women with breast cancer, whereas other studies failed to find this effect. Because most breast cancer deaths are attributable to metastases, we hypothesized that aspects of the...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-08-15 00:00:00
abstract::The ether lipid analogue 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) has been shown to be a direct inhibitor of Swiss 3T3 fibroblast and BG1 ovarian adenocarcinoma cell cytosolic phosphoinositide selective phospholipase C (PIPLC) using [3H]-phosphatidylinositol-(4, 5)-bisphosphate ([3H]PIP2) as the ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-05-15 00:00:00
abstract::Cancer procoagulant (CP) is a Mr 68,000 cysteine proteinase that initiates blood coagulation and is expressed by a variety of malignant cells but not by normally differentiated cells. Polyclonal immunoglobulin G and monoclonal immunoglobulin M antibodies were developed to purified CP and used to develop an enzyme-link...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
abstract::We examined the role of constitutional genetic variation at the UDP-glucuronosyltransferase (UGT) 1A1 locus in breast cancer susceptibility. The UGT1A1 enzyme is a major UGT involved in estradiol glucuronidation. To date, four UGT1A1 variant alleles characterized by a variation in the number of TA from five through ei...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-02-15 00:00:00
abstract::ABL 364 is a murine monoclonal IgG3 antibody directed against the Lewis Y carbohydrate antigen (Le(y)) expressed on the surface of many epithelial cell tumors. The antibody mediates cytotoxicity via activation of human complement or human effector cells, and has been evaluated in several clinical trials including two ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-03-01 00:00:00
abstract::Chloroethylnitrosoureas induce reactive O6-guanine adducts in DNA that can form either interstrand cross-links or a covalent complex with the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). To test our hypothesis that these end-products are formed from the common precursor, 1-O6-ethanoguanine, we com...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-11-01 00:00:00
abstract::Transformation with ras oncogenes results in increased radiation sur vival in many but not all cells. In addition, prenyltransferase inhibitors which inhibit ras proteins by blocking posttranslational modification radiosensitize cells with oncogenic ras. These findings suggest that oncogenic ras contributes to intrins...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract::Transcription factor p53 and phosphatase PTEN are two tumor suppressors that play essential roles in suppression of carcinogenesis. However, the mechanisms by which p53 mediates anticancer activity and the relationship between p53 and PTEN are not well understood. In the present study, we found that pretreatment of mo...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-4184
更新日期:2005-08-01 00:00:00
abstract::DNA mismatch binding in vitro, resistance to DNA methylation damage, and spontaneous mutation rates were examined in human colorectal adenocarcinoma cell lines. Of 11 cell lines, 3 (DLD1, HCT15, and LoVo) were defective in mismatch binding. All three lines had a mutator phenotype. These properties indicate that DLD1 a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract::Loss of imprinting (LOI) of the insulin-like growth factor II (IGFII) gene is a frequent phenomenon in colorectal tumor tissues. Previous reports indicated that subjects with colorectal neoplasias show LOI of IGFII in circulating lymphocytes. Furthermore, LOI of IGFII is strongly related to the methylation of a differ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-3020
更新日期:2009-07-01 00:00:00
abstract::Rabbit skin was infected with Shope papilloma virus and grafted orthotopically to nude mice. Typical Shope rabbit papillomas developed in most of the grafts, but similarly treated nude mouse skin grafts were not altered. These results demonstrated that xenogeneic tissues retained susceptibility to oncogenic agents aft...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::Cell proliferation kinetics during growth of an estrogen receptor-positive human breast carcinoma cell line, T-47D, was defined, and some factors which modify its response to tamoxifen were investigated in vitro. T-47D cells were estrogen responsive when grown in charcoal-stripped fetal calf serum, but the addition of...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-06-01 00:00:00
abstract::Anguidine is a fungal metabolite with antitumor activity in a murine colon cancer model. Because of disappointing results in clinical trials, we analyzed the lethal and cytokinetic effects of anguidine on cultured human colon cancer cells. The studies revealed a moderate reduction in survival only after prolonged drug...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-10-01 00:00:00
abstract::Biallelic somatic mutations of TCF1 coding for hepatocyte nuclear factor 1alpha (HNF1alpha) are found in 50% of the hepatocellular adenoma (HCA) cases usually associated with oral contraception. In rare cases, HNF1alpha germ line mutations could also predispose to familial adenomatosis. In order to identify new geneti...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3947
更新日期:2007-03-15 00:00:00
abstract::The effect of the adenosine diphosphoribosyltransferase inhibitors, the substituted benzamides, on the cytotoxicity of 6-thioguanine (6TG) was investigated. Nontoxic concentrations of benzamides potentiated the cytotoxicity of 6TG with a dose enhancement factor of 2, producing a 6-fold increase in cell killing at 10% ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-10-15 00:00:00
abstract::In 10 separate experiments, mice with established chemically induced or UV light-induced skin papillomas were treated continuously with green tea in the drinking water or with i.p. injections of a green tea polyphenol fraction or (-)-epigallocatechin gallate three times a week for 4-10 weeks. Partial tumor regression ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
abstract::Nm23-H1 has been identified as a metastasis suppressor gene, but its protein interactions have yet to be understood with any mechanistic clarity. In this study, we evaluated the proteomic spectrum of interactions made by Nm23-H1 in 4T1 murine breast cancer cells derived from tissue culture, primary mammary tumors, and...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-0368
更新日期:2013-10-01 00:00:00
abstract::Angiostatin, a proteolytic fragment of plasminogen, is a potent angiogenesis inhibitor able to suppress tumor growth and metastasis through inhibition of endothelial cell proliferation and migration. Previously, we showed that angiostatin binds and inhibits F(1)F(o) ATP synthase on the endothelial cell surface and tha...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-2806
更新日期:2006-01-15 00:00:00
abstract::The possible contribution of endocrine disrupters to human disease, particularly those compounds that modulate the estrogen receptor (ER), has recently drawn considerable attention. The tissue specificity of effects mediated by the ER is well recognized, although the mechanism of this specificity is not understood suf...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-07-01 00:00:00
abstract::Melanoma is a disease characterized by lesions that activate ERK. Although 70% of cutaneous melanomas harbor activating mutations in the BRAF and NRAS genes, the alterations that drive tumor progression in the remaining 30% are largely undefined. Vemurafenib, a selective inhibitor of RAF kinases, has clinical utility ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-2625
更新日期:2014-04-15 00:00:00
abstract::Increased activity, membrane association, and secretion of cathepsin B have been shown to correlate positively with invasiveness and the metastatic properties of many tumor entities. Cathepsin B is able to directly facilitate invasion by degrading extracellular matrix components or to indirectly facilitate invasion by...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-12-01 00:00:00
abstract::It has been shown that the systemic administration of lymphokine-activated killer (LAK) cells with recombinant interleukin 2 (RIL-2) is effective in reducing the number of established pulmonary and hepatic metastases in murine models. Similarly, this modality of therapy has been proven effective against certain select...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract::Whether oncogenic human papilloma viruses (HPVs) are involved in the pathogenesis of prostate cancers has been a subject of great controversy. To clarify the contradictory results of investigations, with the aim of detecting viral nucleic acids in prostate cancers, we have carried out a comparative quantitation of the...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-02-15 00:00:00
abstract::This study identifies ataxia-telangiectasia mutated (ATM) as a further component of the complex signaling network of radiation-induced DNA damage in nontargeted bystander cells downstream of ataxia-telangiectasia and Rad3-related (ATR) and provides a rationale for molecular targeted modulation of these effects. In dir...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0545
更新日期:2008-09-01 00:00:00
abstract::Single-chain antigen-binding proteins, or sFvs, represent potentially unique molecules for targeted delivery of drugs, toxins, or radionuclides to a tumor site. In previous studies (Cancer Res., 51:6363-6371, 1991) using a human colon carcinoma xenograft model, it was demonstrated that the sFv has an extremely rapid p...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-06-15 00:00:00
abstract::A recently developed non-ionic surfactant called Solutol HS 15 (poly-oxyethylene esters of 12-hydroxystearic acid), with low toxicity in vivo, was shown to reverse completely the multidrug resistance of KB 8-5 and KB 8-5-11 human epidermoid carcinoma cells in vitro but did not potentiate drug toxicity in drug-sensitiv...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::A novel, substituted 4-quinolinecarboxylic acid (NSC 339768) demonstrated antitumor activity against L1210 leukemia and B16 melanoma in the National Cancer Institute's Developmental Therapeutics Program. An extensive analogue synthesis program was initiated; over 200 derivatives were synthesized and tested for antican...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-11-01 00:00:00
abstract::Using whole viable human colon carcinoma HT29 cells as immunogen, we produced a monoclonal antibody (mAb) termed 69-6-5. The antibody was functionally selected on its anti-cell-spreading activity. By immunoprecipitation of surface radiolabeled cell lysates from HT29-D4 cells (an HT29 cell clone), mAb 69-6-5 recognized...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-04-15 00:00:00
abstract::The detection of tumor suppressor gene promoter methylation in sputum-derived exfoliated cells predicts early lung cancer. Here, we identified genetic determinants for this epigenetic process and examined their biologic effects on gene regulation. A two-stage approach involving discovery and replication was used to as...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-3194
更新日期:2012-02-01 00:00:00
abstract::Chimeric antigen receptor (CAR) T-cell therapy is an emerging immunotherapy against several malignancies including glioblastoma, the most common and most aggressive malignant primary brain tumor in adults. The challenges in solid tumor immunotherapy comprise heterogenously expressed tumor target antigens and restricte...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-1788
更新日期:2018-02-15 00:00:00