Abstract:
:The in vitro effects of deoxyadenosine and an adenosine deaminase inhibitor, deoxycoformycin, on the synthesis of DNA and the metabolism of purines were investigated in human leukemic T-cells. In the presence of 10 microM deoxycoformycin, the synthesis of DNA was completely inhibited by concentrations of deoxyadenosine of 10 microM or greater. In contrast, the synthesis of DNA in normal bone marrow cells was not inhibited in the presence of up to 20 microM deoxycoformycin and up to 10 microM deoxyadenosine. Following incubation of leukemia T-cells with deoxycoformycin and deoxyadenosine, there was a significant rise in the concentration of deoxyadenosine 5'-triphosphate which was accompanied by reductions in the concentrations of adenosine 5'-triphosphate and guanosine 5'-triphosphate, as revealed by high-pressure liquid chromatographic analysis. The effects of deoxycoformycin on T-cell leukemia were examined in vivo. A patient with acute T-cell leukemia in the terminal stage received five daily injections of 250 micrograms of deoxycoformycin per kg. Among the noted changes, most prominent was the drop in the leukocyte count. Initially, the cell count rose from 7,200 cells/microliters on Day 1 to 120,000 cells/microliters on Day 3. On Day 5, the cell count began to decline and reached a nadir of 600 cells/microliter on Day 10. The leukocyte count remained below 1,000 cells/microliter through Day 12. The reduction in cell count was preceded by a decline in the incorporation of [3H]thymidine in the cells, which dropped to negligible amount by Day 7. The other prominent change was a decrease in adenosine deaminase activity in both red cells and leukemic cells. Adenosine deaminase activity of red cells dropped to 5% on Day 4, and that of leukemic cells dropped to 59% on Day 5. In addition, there were considerable alterations in the concentrations of purine metabolites which were characterized by a progressive reduction in the concentrations of total purine metabolites, especially adenosine 5'-triphosphate, and a transient rise in the concentrations of deoxyadenosine 5'-triphosphate, adenosine 5'-monophosphate, and adenosine 5-diphosphate. These findings suggest that treatment with deoxycoformycin may be of therapeutic value for T-cell leukemia. It may provide opportunities for studying the purine metabolism in T-leukemic cells which could lead to better approaches to treatment.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Yu AL,Bakay B,Kung FH,Nyhan WLsubject
Has Abstractpub_date
1981-07-01 00:00:00pages
2677-82issue
7eissn
0008-5472issn
1538-7445journal_volume
41pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Mitomycin C (MMC) is an anticancer drug that requires reductive activation to exert its toxicity. MMC is known to cross-link DNA that contributes significantly to the cytotoxicity and consequent cell death. Cytosolic NADPH:quinone oxidoreductase 1 (NQO1) and microsomal enzymes have been shown to mediate MMC-induced DN...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-09-15 00:00:00
abstract::Loss of chromosome 10q is a frequently observed genetic defect in prostate cancer. Recently, the PTEN/MMAC1 tumor suppressor gene was identified and mapped to chromosome 10q23.3. We studied PTEN structure and expression in 4 in vitro cell lines and 11 in vivo xenografts derived from six primary and nine metastatic hum...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
abstract::PARP-1 is a nuclear protein that has important roles in maintenance of genomic integrity. During genotoxic stress, PARP-1 recruits to sites of DNA damage where PARP-1 domain architecture initiates catalytic activation and subsequent poly(ADP-ribose)-dependent DNA repair. PARP-1 inhibition is a promising new way to sel...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-1701
更新日期:2014-01-01 00:00:00
abstract::The ErbB2 receptor tyrosine kinase is overexpressed in approximately 25% of breast tumors and contributes to poor patient prognosis and therapeutic resistance. Here, we examine the role of the recently discovered ErbB negative regulator LRIG1 in ErbB2(+) breast cancer. We observe that LRIG1 protein levels are signific...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-6316
更新日期:2008-10-15 00:00:00
abstract::The content of cholesterol and cholesterol ester as well as the levels of acyl coenzyme A:cholesterol acyltransferase activity were determined in the microsomes from Morris hepatomas 7777, 5123D, and 7787. The free cholesterol content, expressed per mg microsomal protein, was significantly increased only in the micros...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract::Regulation of tyrosine aminotransferase gene expression was studied in an adult rat hepatocyte line (RALA255-10G) which is temperature sensitive for the maintenance of the differentiated liver phenotype. Glucocorticoid hormones such as cortisol were necessary for expression of the aminotransferase gene. In the absence...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-10-15 00:00:00
abstract::The potential to heighten the efficacy of antiangiogenic agents was explored in this study based on active targeting of tumor cells overexpressing the gonadotropin-releasing hormone receptor (GnRH-R). The rational design pursued focused on five analogues of a clinically established antiangiogenic compound (sunitinib),...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-2138
更新日期:2016-03-01 00:00:00
abstract::To analyze the humoral immune response to melanoma, human-mouse hybridomas were generated by the fusions of regional lymph node lymphocytes of patients with the mouse myeloma cell line M5. Six stable hybridomas were cloned from six separate lymphocyte parents obtained from three patients. Ascites were obtained from nu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-05-01 00:00:00
abstract::Steroid sulfatase (STS) hydrolyzes several sulfated steroids such as estrone sulfate, dehydroepiandrosterone sulfate, and cholesterol sulfate. In the present study, we have measured STS mRNA levels in 97 breast cancers by reverse transcription-PCR using a fluorescent primer in the presence of an internal standard RNA ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-01-15 00:00:00
abstract::Genetic alterations that occur in human breast cancers are believed to be of importance for initiation as well as progression of the disease. In order to find a genetic alteration that may be used as a prognostic marker, 82 familial breast carcinomas were analyzed for loss of constitutional heterozygosity at polymorph...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-08-15 00:00:00
abstract::Some, but not all, epidemiological studies have suggested that dichlorodiphenyltrichloroethane (DDT) may play a role in the development of breast cancer. These investigations have been conducted in countries where this substance has been banned for at least 20 years. We conducted a study in Mexico, a country in which ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract::The cytokine-inducible endothelial cell adhesion receptor E-selectin has been implicated in cancer metastasis. Previously, we reported that experimental liver metastasis of Lewis lung carcinoma subline H-59 cells could be abrogated in animals treated with an anti-E-selectin antibody. To gain further insight into the f...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-03-15 00:00:00
abstract::Pheophorbide a (PhA), a chlorophyll catabolite, was shown to be an ABCG2 substrate based on Abcg2(-/-) knockout mouse studies (J. W. Jonker et al., Proc. Natl. Acad. Sci. USA, 99: 15649-15654, 2002). We developed a functional assay for ABCG2 using PhA and the ABCG2 inhibitor fumitremorgin C. In selected cell lines exp...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-3298
更新日期:2004-02-15 00:00:00
abstract::DNA probes prepared from human O6-methylguanine-DNA methyltransferase complementary DNA were hybridized to mRNA isolated from human liver and fifteen human tumor cell lines proficient (Mer+) or deficient (Mer-) in transferase activity. Liver and Mer+ cells contained levels of transferase-specific mRNA that correlated ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-12-15 00:00:00
abstract::Recent studies have demonstrated that cytochrome c plays an important role in cell death. In the present study, we report that teniposide and various other chemotherapeutic agents induced a dose-dependent increase in the expression of the mitochondrial respiratory chain proteins cytochrome c, subunits I and IV of cyto...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-02-01 00:00:00
abstract::Lipid peroxidation is considered a unifying mechanistic pathway through which known risk factors induce renal cell carcinoma (RCC). We hypothesized that genes selected a priori for their role in lipid peroxidation would modify cancer risk. We genotyped 635 single nucleotide polymorphisms (SNP) in 38candidate genes in ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-1734
更新日期:2009-10-15 00:00:00
abstract::The value of extracellular pH (pH(e)) in tumors is an important factor in prognosisand choice of therapy. We demonstrate here that pH(e) can be mappedin vivo in a rat brain glioma by (1)H magnetic resonance spectroscopic imaging (SI) of the pH buffer (+/-)2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA). (1)H SI...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-09-01 00:00:00
abstract::Protein kinase C (PKC) has been implicated in enhancing cellular sensitivity to cis-diamminedichloroplatinum(II) (CP). We have synthesized a series of novel analogues of lyngbyatoxin A (7-linalylindolactam V), a natural tumor promoter and a potent activator of PKC, and investigated the effects of these synthetic compo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-05-15 00:00:00
abstract::Fresh surgical explants of human carcinomas were implanted as first transplant generation xenografts under the kidney capsule of mice. Immunocompetent and immune-deficient mice were compared for their ability to support the persistence and growth of these xenografts. Consistent growth of tumor xenografts could not be ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract::Cancer is a leading cause of mortality throughout the world and new treatments are urgently needed. Recent studies suggest that bone marrow-derived mesenchymal stem cells (MSC) home to and incorporate within tumor tissue. We hypothesized that MSCs engineered to produce and deliver tumor necrosis factor-related apoptos...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-4698
更新日期:2009-05-15 00:00:00
abstract::Samples of three nonmalignant and seven leukemic human cells were examined for DNA polymerase activity that could be identified as RNA tumor virus reverse transcriptase. Experiments on virus-infected model animal cells provided the basis for cell fractionation procedures, and reconstituted systems of known virus, adde...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-06-01 00:00:00
abstract::Transcriptional regulator YAP is activated in multiple human cancers and plays critical roles in tumor initiation, progression, metastasis, and drug resistance. However, therapeutic targeting of the Hippo-YAP pathway has been challenging due to its low druggability and limited knowledge of YAP regulation in cancer. He...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-1339
更新日期:2019-12-15 00:00:00
abstract::Pancreatic cancer, one of the deadliest human malignancies, is almost invariably associated with the presence of an oncogenic form of Kras. Mice expressing oncogenic Kras in the pancreas recapitulate the stepwise progression of the human disease. The inflammatory cytokine interleukin (IL)-6 is often expressed by multi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-1558-T
更新日期:2013-10-15 00:00:00
abstract::N4G3, a cell line that overexpresses translation initiation factor eIF4G, one of the components of eIF4F, was made by stable transfection of the human eIF4G cDNA into NIH3T3 cells. The cells expressed 80-100 times greater levels of eIF4G mRNA than did NIH3T3 cells. N4G3 cells formed transformed foci on a monolayer of ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-11-15 00:00:00
abstract::We tested the influence of recombinant human interleukin (rhIL)-l3 and rhIL-4 on clonal growth of human breast cancer cell lines. rhIL-13 and rhIL-4 inhibited clonal growth of three of nine lines to approximately 50% of controls (ED50, 0.5 ng/ml). rhIl-13 reduced [3H]thymidine incorporation in all three cell lines: tw...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::Advocates bring unique and important viewpoints to the cancer research process, ensuring that scientific and medical advances are patient-centered and relevant. In this article, we discuss the benefits of engaging advocates in cancer research and underscore ways in which both the scientific and patient communities can...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-18-1600
更新日期:2018-10-15 00:00:00
abstract::Low-level methotrexate (MTX) resistance (less than 20-fold) was induced by gradual selection pressure in four human head and neck squamous cell carcinoma lines established in culture from biopsies of patients not previously treated with MTX. Each parental and resistant line was characterized with respect to MTX uptake...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-12-01 00:00:00
abstract::A nationwide study of all 3183 female patients with breast cancer in Israel diagnosed over a 7-year period (1960 to 1966) was conducted. Monthly series analysis showed a clear seasonal pattern in the symptomatology of the disease most pronounced in patients younger than 55 years, in all ethnic groups, mainly confined ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-02-01 00:00:00
abstract::The single-dose toxicokinetics of N-nitrosomethyl(2-hydroxyethyl)amine (NMHA) has been characterized in 8-week-old Fischer 344 rats by analysis using high-performance liquid chromatography of serial blood samples. An i.v. bolus dose of 0.6 mumol/kg to male rats revealed biphasic first-order elimination with a terminal...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::To define genetic determinants of tumor cell resistance to the cytotoxic action of tumor necrosis factor alpha (TNF), we have applied cDNA microarrays to a human breast carcinoma TNF-sensitive MCF7 cell line and its established TNF-resistant clone. Of a total of 5760 samples of cDNA examined, 3.6% were found to be dif...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-1735
更新日期:2004-01-15 00:00:00