Abstract：
:A subline of H35 hepatoma cells has been developed which exhibits 80-fold resistance to 5,10-dideazatetrahydrofolate, an antifolate which inhibits glycinamideribonucleotide transformylase. The cells are cross-resistant to methotrexate, an inhibitor of dihydrofolate reductase and 10-propargyl-5,8-dideazafolate and its 2-desamino-2-methyl derivative, both inhibitors of thymidylate synthase. The resistant cells are characterized by an impaired activity of the reduced folate transport system which affects cellular import of methotrexate, 5,10-dideazatetrahydrofolate, and 2-desamino-2-methyl-10-propargyl-5,8-dideazafolate but not 10-propargyl-5,8-dideazafolate. In addition, the resistant cells exhibit a severalfold increased activity of gamma-glutamyl hydrolase, the enzyme which cleaves the intracellular polyglutamate derivatives of the antifolates. Evidence for the involvement of gamma-glutamyl hydrolase in resistance is derived from the observation that polyglutamate derivatives of 10-propargyl-5,8-dideazafolate in resistant cells are maintained at one-third the amount of that in parental cells in the presence of the same extracellular concentration. This is the first observation that an increase in gamma-glutamyl hydrolase contributes to acquired resistance to antifolates.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Rhee MS,Wang Y,Nair MG,Galivan Jsubject
Has Abstractpub_date
1993-05-15 00:00:00pages
2227-30issue
10 Suppleissn
0008-5472issn
1538-7445journal_volume
53pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:In most patients with chronic myeloid leukemia (CML), the disease can be kept under control using the BCR/ABL kinase inhibitor imatinib. Nevertheless, resistance or intolerance to imatinib and other BCR/ABL inhibitors may occur during therapy. Therefore, CML research is focusing on novel targets and targeted drugs. Po...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-2181
更新日期：2010-02-15 00:00:00
abstract：:Transfection of C3H/10T1/2 cells with either a c-myc or an activated c-Ha-ras gene decreased the cellular dependence for serum-derived factors to proliferate in monolayer. The c-myc-transfected cells did, however, require a high plasma concentration for significant growth, while the ras transfectants grew extremely we...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-05-01 00:00:00
abstract：:Accumulating evidence suggests that the p53 gene is a good target for molecular epidemiological studies to search for risk factors in carcinogenic events. The lung cancer incidence for females in Hong Kong is unusually high, ranking among the highest in the world despite a low percentage with a history of smoking. To ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-11-15 00:00:00
abstract：:Southern analysis has shown that DNA from 25% of primary estrogen receptor (ER) alpha-negative breast tumors displays aberrant methylation at one site within the ER gene CpG island. To examine more sites and increase sensitivity, we developed a methylation-specific PCR assay to map methylation of the entire ER CpG isl...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-06-15 00:00:00
abstract：:For two decades, the antigen recognized by the Pathologische Anatomie Leiden-Endothelium (PAL-E) monoclonal antibody, a standard vascular endothelial cell marker, has remained elusive. Here, we used a combinatorial phage display-based approach ("epitope mapping") to select peptides binding to the original PAL-E antibo...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-2737
更新日期：2007-10-15 00:00:00
abstract：:In 1984, we reported that while immunoreactive levels of serum alpha-1 proteinase inhibitor (API) increased significantly in nine patients with advanced solid tumors, the functional activity of the inhibitor, as measured by the serum trypsin inhibitory capacity, did not increase proportionately. This suggested that a ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-02-15 00:00:00
abstract：:We examined the genetic requirements for the Myc family of oncogenes in normal Sonic hedgehog (Shh)-mediated cerebellar granule neuronal precursor (GNP) expansion and in Shh pathway-induced medulloblastoma formation. In GNP-enriched cultures derived from N-myc(Fl/Fl) and c-myc(Fl/Fl) mice, disruption of N-myc, but not...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-1621
更新日期：2006-09-01 00:00:00
abstract：:In a separate study (F. Courjal et al., Cancer Res., 57: 4360-4367, 1997), we have analyzed by Southern blotting the relationship between DNA amplification and clinicopathological features of breast cancer. Six regions of recurrent amplifications were tested (8p12, 8q24, 11q13, 12q13, 17q12, and 20q13), and the result...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：:Dipeptidyl peptidase IV (DPPIV/CD26) is a multifunctional cell surface aminopeptidase that is widely expressed in different cell types. Our previous study demonstrated a possible link between DPPIV expression and decreased i.p. dissemination and loss of invasive potential of ovarian carcinoma. In this report, we exami...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-05-01 00:00:00
abstract：:High-grade gliomas are characterized by exuberant vascularization, diffuse invasion, and significant chemoresistance, resulting in a recurrent phenotype that makes them impossible to eradicate in the long term. Targeting protumoral signals in the glioma microenvironment could have significant impact against tumor cell...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-0685
更新日期：2014-10-01 00:00:00
abstract：:CD4+ T-cell responses against human tumor antigens are a potentially critical component of the antitumor immune response. Molecular methods have been devised for rapidly identifying MHC class II-restricted tumor antigens and elucidating the recognized epitopes. We describe here the identification of neo-poly(A) polyme...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-10-01 00:00:00
abstract：:Integral membrane proteins are visualized as intramembrane particles (IMP; also called membrane-associated particles) at the cleaved surfaces of freeze-fractured plasma membranes. Topographical distributions of the IMP of urothelial cell membranes in normal human bladder and for a small series of low-grade noninvasive...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-07-01 00:00:00
abstract：:In this study the cytokinetic and antitumor effects of 12-h continuous treatment with 6-thioguanine (TG) were studied in L1210 cells in vivo and in vitro. Loss of clonogenicity in vitro was maximized at a drug concentration of 0.2 microM. Higher drug concentrations produced less cell kill, and the surviving fraction o...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-06-15 00:00:00
abstract：:Progression of prostate cancer is believed to be dependent on angiogenesis induced by tumor cells. 3,3'-Diindolylmethane (DIM) has been shown to repress neovascularization in a Matrigel plug assay and inhibit cell proliferation, migration, invasion, and capillary tube formation of cultured human umbilical vein endothe...
journal_title：Cancer research
pub_type： 杂志文章,收录出版
doi：10.1158/0008-5472.CAN-06-4277
更新日期：2007-04-01 00:00:00
abstract：:Inhibition of angiogenesis has emerged as a key focus for the treatment of cancer, necessitating a better understanding of the downstream molecular targets of angiogenesis inhibitors. Endostatin, thrombospondin-1, fumagillin, and its synthetic derivative, TNP-470, are potent inhibitors of endothelial cell proliferatio...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-10-01 00:00:00
abstract：:Translocation of the bcl-2 gene to the immunoglobulin heavy chain gene is the most common alteration in follicular lymphoma. The result is the deregulated expression of bcl-2 and increased resistance to cell death. Regulation of the immunoglobulin heavy chain gene is controlled in part by four DNase I-hypersensitive r...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-10-15 00:00:00
abstract：:Disruption of one allele for the cytosine-DNA methyltransferase 1 (DNMT1) gene in mice with a germ-line mutation in a tumor suppressor gene was shown previously to reduce tumor formation in juvenile animals. This effect is now reproduced in our studies of mature mice where this genetic DNMT1 reduction leads to a 50% d...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-11-01 00:00:00
abstract：:Preclinical studies have suggested that β-adrenergic signaling is involved in pancreatic cancer progression. Prompted by such studies, we investigated an association between beta-blocker drug use with improved cancer-specific survival in a large, general population-based cohort of patients with pancreatic ductal adeno...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-0108
更新日期：2017-07-01 00:00:00
abstract：:Tumor resistance to cytotoxic drugs is one of the main obstacles to successful cancer therapy. Emerging evidence suggests that chemoresistance is promoted by substances released from dead and damaged cells that activate the host repair program orchestrated by Toll-like receptor-4 (TLR4). TLR4 is often overexpressed in...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-14-3525
更新日期：2015-06-15 00:00:00
abstract：:After 10 years of clinical trials in patients with advanced cancer, monoclonal antibodies (mAbs) against cell surface antigens have not lived up to their initial promise. One such cell surface antigen is the ganglioside GD2. GD2 is richly expressed at the cell surfaces of human neuroblastomas, sarcomas, and melanomas....
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-07-01 00:00:00
abstract：:The ability to accurately distinguish remaining or recurrent high-grade astrocytoma from necrosis or edema following treatment is essential to optimal patient management. Thallium 201 planar gamma-camera imaging has been shown to be helpful in detecting recurrent high-grade astrocytoma; however, due to tissue heteroge...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-07-15 00:00:00
abstract：:The LeY determinant, a difucosylated type 2 blood group-related antigen, is a positional isomer of the Leb blood group antigen and a fucosylated derivative of the LeX antigen. The LeX antigen behaves like an oncodevelopmental tumor-associated antigen in human colon cancer, and extended polyfucosyl LeX antigens are mor...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-11-01 00:00:00
abstract：:In cancer patients and in those at high risk, systemic exposure to agents for therapy or prevention is accompanied by undesirable side effects. We hypothesized that it is possible to prevent and treat breast cancer by introducing anticancer agents into the mammary ductal network. Here, we show the efficacy of intraduc...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-4329
更新日期：2006-01-15 00:00:00
abstract：:Small-molecule inhibitors of PARP1/2, such as olaparib, have been proposed to serve as a synthetic lethal therapy for cancers that harbor BRCA1 or BRCA2 mutations. Indeed, in clinical trials, PARP1/2 inhibitors elicit sustained antitumor responses in patients with germline BRCA gene mutations. In hypothesizing that ad...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-2541
更新日期：2014-01-01 00:00:00
abstract：:The effect of basic fibroblast growth factor (b-FGF), one of the commonest angiogenic factors in various cancer types, on lymphocyte adhesion and transmigration across the endothelial cell monolayer was investigated using human umbilical vein-derived endothelial cells (HUVEC) and type I collagen gel. Forty-eight h exp...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:The anticarcinogenic activities of retinoic acid (RA) are believed to be mediated by the nuclear RA receptor (RAR) and by the RA-binding protein cellular RA-binding protein-II (CRABP-II). In MCF-7 mammary carcinoma cells, growth inhibition by RA entails an early cell cycle arrest followed by induction of apoptosis. He...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-0989
更新日期：2007-01-15 00:00:00
abstract：:It has been suggested that P-glycoprotein (P-gp), an ATP-dependent transporter responsible for classical multidrug resistance, is also a volume-regulated chloride channel. We reexamined this hypothesis by use of whole-cell patch clamp recordings of three matched pairs of cell lines, which were either drug-sensitive or...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
abstract：:The purpose of this study was to determine the effect of route of hepatic administration of drug on the regional pharmacokinetics and systemic exposure of 5-fluorouracil (FUra) and 5-bromo-2-deoxyuridine (BrdUrd). A total of 13 mixed-breed male and female dogs were used in these acute studies. Each dog was administere...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-10-15 00:00:00
abstract：:A link between colitis and colon cancer is well established, but the mechanisms regulating inflammation in this context are not fully defined. Given substantial evidence that hemostatic system components are powerful modulators of both inflammation and tumor progression, we used gene-targeted mice to directly test the...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-3465
更新日期：2010-04-01 00:00:00
abstract：:Risk assessment of dioxins is currently based on induction of liver tumors in rats. The toxicity of dioxins is characterized by large sensitivity differences among animal species and even strains of the same species, which complicates the risk assessment. The significance of these differences in dioxin-induced carcino...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-12-15 00:00:00
