Abstract:
:Earlier studies have shown guanine arabinoside (ara-G) is an effective agent against growth of T-cell lines and freshly isolated human T-leukemic cells. However, poor water solubility of ara-G limits clinical use. 2-Amino-6-methoxypurine arabinoside (506U) is a water-soluble prodrug converted to ara-G by adenosine deaminase. 506U is not a substrate for deoxycytidine kinase, adenosine kinase, or purine nucleoside phosphorylase and is phosphorylated by mitochondrial deoxyguanosine kinase at a rate 4% that of ara-G phosphorylation. Mitochondrial DNA polymerase was the least sensitive to ara-GTP inhibition of the five human DNA polymerases tested. [3H]506U was anabolized to ara-G 5'-phosphates in CEM cells but not to phosphorylated metabolites of 506U. 506U was selective for transformed T over B cells and also inhibited growth in two of three monocytic lines tested. 506U given i.v. to cynomolgus monkeys was rapidly converted to ara-G; the ara-G had a half-life of approximately 2 h. 506U had in vivo dose-dependent efficacy against human T-cell tumors in immunodeficient mice. A Phase 1 trial of 506U against refractory hematological malignancies is now in progress at two study sites.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Lambe CU,Averett DR,Paff MT,Reardon JE,Wilson JG,Krenitsky TAsubject
Has Abstractpub_date
1995-08-01 00:00:00pages
3352-6issue
15eissn
0008-5472issn
1538-7445journal_volume
55pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::The effects of N-5-dimethyl-9-(2-methoxy-4-methylsulfonylamino)-phenylamino-4- acridinecarboxamide (CI-921; NSC 343499), a lipophilic and water-soluble derivative of amsacrine (NSC 249992), on cell viability, growth, clonogenicity, and progression through the cell cycle were investigated in suspension cultures of Frie...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-01-15 00:00:00
abstract::2'-Deoxycoformycin (2'-dCF), a tight-binding inhibitor of adenosine deaminase, was administered to 26 pediatric patients with acute lymphoblastic leukemia in a Phase I study. Doses ranged from 0.25 to 1.0 mg/kg given i.v. for 3 consecutive days. Common toxicity included nausea, vomiting, diarrhea, hepatocellular enzym...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-09-01 00:00:00
abstract::Head and neck squamous cell carcinomas (HNSCC) often metastasize to locoregional lymph nodes, and lymph node involvement represents one of the most important prognostic factors of poor clinical outcome. HNSCCs are remarkably lymphangiogenic and represent a clear example of a cancer that utilizes the lymphatic vasculat...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-3121
更新日期:2015-07-15 00:00:00
abstract::Recent in vitro studies of the epidermal growth factor receptor (EGFR) family have revealed complex signaling interactions involving the production of ligand-mediated heterodimers synergistic for the transformation of cells in vitro. In a series of 70 patients with childhood medulloblastoma, we have used immunohistoch...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract::A clone of a human gastric carcinoma cell line was used to determine whether cells which had survived a treatment with Melphalan would express altered survival responses when treated again with this agent 1 week or more later. Cells were treated for 1 h each week with 2 micrograms/ml (99% lethal dose). After the first...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-06-15 00:00:00
abstract::We and others have established that the developmental Notch receptor signaling pathway is active in breast cancer cell lines, as well as in preinvasive and invasive primary samples. Recently, a role for Notch in regulating the hierarchy of stem and progenitor cells in both normal and cancer epithelium has been elucida...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-10-1559
更新日期:2010-11-15 00:00:00
abstract::Aromatase plays a critical role in breast cancer development by converting androgen to estrogen. In this report, results are presented to demonstrate that estrogen, the product of aromatase, can up-regulate its expression. Estrogen receptor (ER) transient transfection experiments were performed using the SK-BR-3 breas...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00
abstract::Overexpression of interleukin 6, a downstream target of the GBX2 homeobox gene, has been linked to the progression of prostate cancer. The Janus kinase-signal transducers and activators of transcription signaling pathway transmits interleukin 6-mediated signals from cell surface receptors to the target genes in the nu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract::We have explored the therapeutic effects of anti-epidermal growth factor receptor monoclonal antibodies (MAbs) 225 and 528 on well established A431 epidermoid carcinoma xenografts, approximately 400 mm3 (1 cm in diameter) at the start of treatment. In previous reports we demonstrated that MAbs 225 and 528 prevented th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::Analysis of ovarian carcinomas has shown that karyotypes are often highly abnormal and cannot be identified with certainty by conventional cytogenetic methods. In this study, 17 tumors derived from 13 patients were analyzed by a combination of spectral karyotyping (SKY), comparative genomic hybridization (CGH), and ex...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-06-15 00:00:00
abstract::An assay has been developed and measurements of aryl hydrocarbon [benzo(a)pyrene] hydroxylase have been made in peripheral blood monocytes from a human population. Treatment with benz(a)anthracene in cell culture increased aryl hydrocarbon hydroxylase activity from 6.5 to 37-fold in monocytes from each of 25 apparentl...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-06-01 00:00:00
abstract::Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is an angiogenic cytokine expressed by many human and animal tumors. Hypoxia often up-regulates VPF/VEGF expression further. To better define the role of VPF/VEGF in tumor biology, we screened tumorigenic lines for those expressing minimal co...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::Expression of non-self antigens by tumors can induce activation of T cells in vivo, although this activation can lead to either immunity or tolerance. CD8+ T-cell activation can be direct (if the tumor expresses MHC class I molecules) or indirect (after the capture and cross-presentation of tumor antigens by dendritic...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-3163
更新日期:2008-02-15 00:00:00
abstract::Tetrachloro(d,l-trans)-1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) has been considered a prodrug which would be converted rapidly to dichloro(d,l-trans)-1,2-diaminocyclohexaneplatinum(II) [PtCl2(dach)] under physiological conditions. However, the biotransformations of tetraplatin have not been studied in detail. ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::Sequence alterations of mitotic checkpoint genes, hBUB1 and hBUBR1, were examined, and their gene transcripts were quantified using on-line, real-time quantitative reverse transcription-PCR in surgically resected human colorectal cancers and their neighboring normal tissues. Our results reveal a new hBUB1 missense mut...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::The plasma of dogs afflicted with mammary carcinoma was perfused through chambers bearing Staphylococcus aureus Cowan strain I in an attempt to remove tumor-promoting, immunosuppressive immune complexes from the peripheral blood of these animals. In this canine model of spontaneous mammary carcinoma, reduction of brea...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-09-01 00:00:00
abstract::In mice, 4-nitrobenzylidene malononitrile (AG1714), which belongs to the tyrphostin family, reduced toxicity induced by doxorubicin and cisplatin without impairing their antitumor efficacy. AG1714 reduced mortality induced by doxorubicin and cisplatin. It prevented, in a dose-dependent manner, cisplatin-induced nephro...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
abstract::Both clinical and experimental breast tumors often synthesize high levels of prostaglandins, most notably prostaglandin E2 (PGE2). We have reported previously that metastatic murine mammary tumor cells also express a high-affinity PGE2 receptor. We have now shown that the receptor plays a functional role in the metast...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-04-15 00:00:00
abstract::The objective of this investigation was to study the effects of maytansine on the cell cycle kinetics of HeLa cells. The results of this study indicate that maytansine is a very potent mitotic inhibitor and that it has no effect on macromolecular synthesis. Maytansine-induced cytotoxicity was dependent upon the positi...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-08-01 00:00:00
abstract::There is a paucity of data on whether or not women can be reinfected with human papillomavirus (HPV) types to which they were exposed to earlier in life and on the role of natural immunity. The observation of HPV infection at older ages may be explained by the reactivation of a latent infection or new exposure from se...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-0621
更新日期:2010-11-01 00:00:00
abstract::The transformation of murine BALB/c embryonic fibroblasts by murine sarcoma virus, Moloney strain, followed by prolonged treatment with murine interferon, resulted in the appearance of a new cell population (MSV-IF+). These MSV-IF+ cells are characterized by the recovery of a normal phenotype, contact inhibition, and ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-09-01 00:00:00
abstract::The spontaneous development of juvenile-onset ovarian granulosa cell tumors in mice of the SWXJ-9 recombinant inbred strain is a model for juvenile-type granulosa cell tumors that appear in very young girls. To expedite gene discovery in this mouse model of childhood cancer, we did a gene mapping study with the SWXJ-9...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-2992
更新日期:2005-02-15 00:00:00
abstract::Resistance to antineoplastic drugs is a major problem in the clinical management of cancer. Previous studies have demonstrated that the cytotoxicity of certain anticancer drugs is increased by lowering the glutathione (GSH) levels with buthionine sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthe...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-02-01 00:00:00
abstract::Hypoxia initiates numerous intracellular signaling pathways important in regulating cell proliferation, differentiation, and death. In this study, we investigated the pathway that hypoxia uses to activate Akt and inactivate glycogen synthase kinase-3 (GSK-3), two proteins the functions of which are important in cell s...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-03-15 00:00:00
abstract::Medulloblastoma and central nervous system primitive neuroectodermal tumors (CNS-PNET) are aggressive, poorly differentiated brain tumors with limited effective therapies. Using Sleeping Beauty (SB) transposon mutagenesis, we identified novel genetic drivers of medulloblastoma and CNS-PNET. Cross-species gene expressi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-1261
更新日期:2019-03-01 00:00:00
abstract::Specific binding sites for prolactin (PRL) were present in membrane preparations from 7,12-dimethylbenz(a)-anthracene-induced rat mammary tumors. The specific binding of PRL was time and temperature dependent. A significant negative correlation was noted between administered doses of estrogen and the subsequent bindin...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-09-01 00:00:00
abstract::Increase in dietary fat intake has been reported to be associated with progression of hormone-dependent cancers. To explore its mechanism, we examined the effects of fatty acids on the growth of androgen-dependent SC-3 cells cloned from mouse mammary cancer (Shionogi carcinoma 115). Their androgen-dependent growth was...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-12-15 00:00:00
abstract::The s.c.-propagated murine glioma, GL-26, was established in tissue culture. The tissue culture line, with a doubling time of 36 hr, was used as the common source for all tumor cells. Suspensions of the tumor cells were transplanted intracerebrally in mice to produce an anaplastic ependymoblastoma. In vitro 51-Cr cyto...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-03-01 00:00:00
abstract::The cytotoxic activity against human tumor cells of toxic conjugates of Pseudomonas exotoxin with anti-transferrin receptor antibody or epidermal growth factor was potentiated up to 10 to 20-fold by the calcium antagonists verapamil, D-600, and diltiazem and by the lysosomotropic agent beta-glycylphenyl-naphthylamide....
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
abstract::Local irradiation of tumors of rats bearing 3924A hepatomas resulted in more than a doubling of the putrescine levvel and nearly a doubling of spermidine concentration in the serum within 12 hr. Within 24 hr, the putrescine concentration had increased four-fold in the serum, along with a continued increase in the sper...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-02-01 00:00:00