Abstract：
:The effect of culture conditions on the glutamylation of methotrexate by intact H35 hepatoma cells and folylpolyglutamate synthetase (FPGS) activity in the corresponding crude extracts has been examined. The rate of cellular glutamylation of methotrexate observed in rapidly dividing cultures was 4-fold higher than confluent cultures, and was accompanied by an increase in extract FPGS activity (2.2-fold). The depletion of cellular folates produced comparable increases in both cellular methotrexate glutamylation and extract FPGS activity (approximately 1.8-fold). Near-quantitative reductions in cellular methotrexate glutamylation were caused by media additions of reduced folates and methotrexate to confluent cultures of wild-type and folate-depleted H35 cells. However, these produced relatively modest reductions in FPGS activity in the corresponding crude extracts (approximately 50%). Methionine exclusion resulted in a greater than 50% decrease in FPGS activity in crude extracts of these cells compared to extracts of control cultures. The combination of methionine exclusion and folinic acid addition lowered the FPGS activity to less than 25% that of control. The data suggest that the changes in the glutamylation rate of methotrexate in whole cells due to culture conditions such as folate restriction, reduced folate addition, methionine exclusion, and growth state are at least in part a consequence of alterations in FPGS activity. This conclusion is consistent with the proposition that the metabolism of slow-acting substrates for FPGS (such as 4-amino antifolates and their corresponding polyglutamates) may be sensitive to changes in enzyme levels or activity (Cook et al., Biochemistry, 26: 530-539, 1987). Analysis of the products formed by FPGS from extracts using methotrexate as the substrate revealed no significant amounts of polyglutamate species higher than 4-NH2-10-CH3-PteGlu3. In contrast, when using the thymidylate synthase inhibitor N10-propargyl-5,8-dideazafolic acid as the starting substrate under identical assay conditions, FPGS from extracts catalyzed the formation of predominantly long chain polyglutamate derivatives (Glu4 and higher). These results reflect the relative efficacy of methotrexate and N10-propargyl-5,8-dideazafolic acid, as well as their polyglutamate derivatives, as substrates for FPGS.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Johnson TB,Nair MG,Galivan Jsubject
Has Abstractpub_date
1988-05-01 00:00:00pages
2426-31issue
9eissn
0008-5472issn
1538-7445journal_volume
48pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:The intranuclear mitosis of the plasmodial nuclei of myxomycetes permits the observation of defects in chromosomal repartition which would probably be lethal in other eukaryotic cells with open mitosis. We found that antitumoral platinum-amine compounds perturbed late mitotic events and induced the formation of giant ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-02-01 00:00:00
abstract：:Methylation associated inactivation of RASSF1, a putative tumor suppressor identified at 3p21.3, has been frequently observed in several human malignancies, including lung and breast cancers. To explore the penetrance of RASSF1 in gastric carcinogenesis, we performed expression and mutation analyses of 3 isotypes of R...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
abstract：:Human p29 is a newly identified nuclear protein whose function is largely undetermined. We found that p29 associated with chromatin, interacted with MCM3, and localized with proliferating cell nuclear antigen foci in the S phase. Silencing of p29 using small interfering RNA duplexes reduced DNA synthesis and increased...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-3229
更新日期：2006-09-01 00:00:00
abstract：:Checkpoint inhibitors are relatively inefficacious in head and neck cancers, despite an abundance of genetic alterations and a T-cell-inflamed phenotype. One significant barrier to efficacy may be the recruitment of myeloid-derived suppressor cells (MDSC) into the tumor microenvironment. Here we demonstrate functional...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-16-2534
更新日期：2017-05-15 00:00:00
abstract：:Human kallikrein 10 (hK10) is a secreted serine protease that is highly expressed in ovarian tissue. We hypothesized that hK10 might represent a novel serological marker for ovarian cancer. We quantified by immunoassay, hK10 in sera from 97 normal women (controls), 141 patients with benign gynecologic diseases, and 14...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-02-15 00:00:00
abstract：:The tumor-associated antigen MUC1 is overexpressed and underglycosylated in human adenocarcinomas of diverse origins, such as breast, ovary, and colon. We isolated and describe five human single-chain (sc) Fv antibodies specific for the MUC1 variable number of tandem repeats region isolated by in vitro selection from ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-10-01 00:00:00
abstract：:Colitis-associated cancer (CAC) is a complication of inflammatory bowel disease (IBD). Binding of extracellular ATP to the purinergic receptor P2RX7 has emerged as a critical event in controlling intestinal inflammation, acting to limit elevation of proinflammatory mast cells and cytokines and promote survival of regu...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-1778
更新日期：2015-03-01 00:00:00
abstract：:A novel chromosomal translocation, t(2;11)(q31;p15), was identified in a patient with therapy-related acute myelogenous leukemia (t-AML). Fluorescence in situ hybridization experiments mapped the breakpoint near NUP98; Southern blot analysis demonstrated that the nucleoporin gene NUP98 was disrupted by this translocat...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-10-01 00:00:00
abstract：:The possible influence of phenobarbital and phenytoin treatment on cancer risk was investigated in a case-control study nested in a cohort of 8004 epileptic patients in Denmark. Information on anticonvulsive treatments was abstracted for 95% of 60 patients with cancers of the liver and biliary tract or malignant lymph...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-01-15 00:00:00
abstract：:N-Demethylated metabolites of the antineoplastic agent hexamethylmelamine were synthesized, and their toxicities and antitumor activities were determined in vivo. Determinations of the lethal dose for 10% of the male C57BL X DBA/2 F1 (hereafter called BD2F1) mice showed hexamethylmelamine toxicity to be decreased by N...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-10-01 00:00:00
abstract：:The clinical utility of cisplatin to treat human malignancies is often limited by the development of drug resistance. We have previously shown that cisplatin-resistant human KB adenocarcinoma cells that are cross-resistant to methotrexate and heavy metals have altered endocytic recycling. In this work, we tracked lipi...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-3436
更新日期：2006-02-15 00:00:00
abstract：:Transforming growth factor-beta (TGF-beta) functions as a tumor suppressor of the prostate through mechanisms that remain unresolved. Although TGF-beta receptors directly activate both Smads 2 and 3, to date, Smad3 has been shown to be the essential mediator of most Smad-dependent TGF-beta responses, including control...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-3961
更新日期：2009-03-15 00:00:00
abstract：:In the absence of excision repair, doxorubicin caused a striking (41-fold) increase in the frequency of large deletion mutations extending from the lac operator (lacO) into the lac repressor gene (lacI) of Escherichia coli. In contrast, there was only a 2-fold increase in the frequency of small deletions despite a 3-f...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Human mammary epithelial cells (HMEC) grown under standard cell culture conditions enter a growth phase referred to as selection, but a subpopulation is able to escape from arrest and continue to proliferate. These cells, called post-selection or variant HMECs, may be derived from progenitor cells found in normal mamm...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-1284
更新日期：2007-12-15 00:00:00
abstract：:Steroid and xenobiotic receptor (SXR) or human pregnane X receptor (hPXR) has been shown to play an important role in the regulation of genes related to xenobiotic detoxification, such as cytochrome P450 3A4 and multidrug resistance gene 1. Cytochrome P450 enzymes, conjugation enzymes, and transporters are all conside...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-1070
更新日期：2006-01-01 00:00:00
abstract：:A series of mouse mammary tumor subpopulation lines were compared for growth properties and sensitivity to chemotherapeutic drugs when grown as boluses in a collagen gel matrix versus in monolayer culture. Although the cell lines exhibited characteristic rates of bolus expansion in collagen, this growth was not parall...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-09-01 00:00:00
abstract：:Replicative senescence limits the number of times primary cells can divide and is therefore regarded as a potential checkpoint for cancer progression. The majority of studies examining changes of gene expression upon senescence have been made with stationary senescent cells. We wanted to study the transition from norm...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.can-03-1872
更新日期：2004-01-15 00:00:00
abstract：:The concentration of estrogenic, androgenic, progestational, and adrenocortical steroid hormones in body fluids of mature intact Sprague-Dawley female rats was increased by s.c. implantation of 5 to 7 mg NaCl pellets containing 1 to 20% steroid 48 hr before administration p.o. of either 7,12-dimethylbenz(a) anthracene...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-05-01 00:00:00
abstract：:Two populations of nuclear androgen receptors have been characterized in human prostatic tissue, and the levels and proportions of each were found to differ in normal prostates, benign hyperplastic prostates (BPH), and malignant prostates. A significant percentage (35 to 50%) of total nuclear androgen receptors was as...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：:Endometrial carcinoma is associated with antecedent simple and complex hyperplasia, and the endometrium is a target tissue for the action of cytokines and growth factors. Transforming growth factor (TGF)-beta s are potent cellular growth and differentiation regulatory factors. Therefore, we investigated the potential ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:Plasmids may have unique advantages as a gene delivery system. However, a major obstacle is the low in vivo transduction efficiency. In this study, an electroporation-based gene transduction approach was taken to study the effect of interleukin (IL)-2 or IL-12 gene transduction on the growth of experimental murine tum...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-04-15 00:00:00
abstract：:In the immediately preceding paper, we demonstrated that the microvasculature supplying peritoneal lining tissues of mice bearing either of two transplantable ascites carcinomas was hyperpermeable to circulating macromolecules. Solid tumors have been shown to exhibit similar levels of microvascular hyperpermeability, ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-01-15 00:00:00
abstract：:A growing number of observations has suggested that plasmacytoid dendritic cells (pDC) play a critical role in tumor biology. In patients, infiltration of tumors by pDCs generally correlates with a poor prognosis, suggesting that pDCs may play an important role in the host-tumor relationship. Here, we analyze the infl...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-2719
更新日期：2018-06-01 00:00:00
abstract：:To understand the skeletal metastatic pattern of non-small cell lung cancer, we developed a stable high-expression green fluorescent protein (GFP) transductant of human lung cancer cell line H460 (H460-GFP). The GFP-expressing lung cancer was visualized to metastasize widely throughout the skeleton when implanted orth...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-10-01 00:00:00
abstract：:Transduction of mitogenic signals in cells can be mediated by molecules derived from the synthesis and breakdown of the major membrane phospholipid, phosphotidylcholine. Studies were performed on human mammary epithelial cells in culture to understand the impact of malignant transformation and progression on membrane ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-01-01 00:00:00
abstract：:Structural alterations of the p53 gene were investigated in tissue specimens of gastric and cervical cancers and in cell lines of gastric, esophageal, and cervical cancers, by polymerase chain reaction-single-strand conformation polymorphism analysis. Two of the four gastric cancer metastases and four of the eight cel...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:Cancer cells with germline deleterious mutations of BRCA1 or BRCA2 are deficient in homologous recombination repair and therefore sensitive to PARP inhibitor treatment. However, wild-type BRCA1/2-expressing cells with defects in other DNA damage repair pathway components may also exhibit "BRCAness," which in combinati...
journal_title：Cancer research
pub_type： 评论,杂志文章
doi：10.1158/0008-5472.CAN-20-1451
更新日期：2020-07-15 00:00:00
abstract：:Oxidative stress exerted by superoxide-generating (redox-cycling) agents such as paraquat triggers the soxRS regulon of Escherichia coli. In this system, SoxR protein is the redox-sensitive activator of the soxS gene, the product of which then activates the approximately 10 promoters of this regulon. We found that 4-n...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-07-15 00:00:00
abstract：:Two murine monoclonal antibodies, 2H6G5 (IgM) and 4A9E10 (IgG3), were obtained by using either cultured human hepatocellular carcinoma cells (PLC/PRF/5) or the acidic glycolipid mixture prepared from the same cells as immunogens. The antigen in PLC/PRF/5 cell membranes recognized by both antibodies was identified as a...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:The selective pressures leading to cancers with mutations in both KRAS and PIK3CA are unclear. Here, we show that somatic cell knockin of both KRAS G12V and oncogenic PIK3CA mutations in human breast epithelial cells results in cooperative activation of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protei...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-12-1578
更新日期：2013-06-01 00:00:00
