Abstract:
:Two aminoanthraquinone analogs 1,4-bis(2-[(2-hydroxyethyl)amino]ethylamino)-9,10-anthracenedione (HAQ) and 1,4-dihydroxy-5,8-bis(2-[(2-hydroxyethyl)amino]ethylamino]-9,10-anthracenedione (DHAQ) have been shown to possess similar therapeutic activities against experimental tumors but different toxicities to the animals. In this study, the genotoxic effects of these two drugs and a new analog, 1,4-dihydroxy-5,8-bis(2-[(2-hydroxyethyl)amino]ethylamino]-9,10-anthracenedione diacetate, were analyzed by using mammalian cell cytogenetic assays (chromosome breakage and sister chromatid exchanges) as well as bacterial mutagenesis assays. The experimental therapeutic activities of these drugs in vivo correlated well with their in vitro genetic toxicities as revealed by cytogenetic assays; i.e., the drug with the highest therapeutic activity (DHAQ) was most active in inducing chromosome damage. DHAQ was also more genotoxic than Adriamycin. In cytogenetic assays, the activities of all drugs were reduced to different degrees in the presence of a S-9 metabolic system. Dis as revealed by cytogenetic assays; i.e., the drug with the highest therapeutic activity (DHAQ) was most active in inducing chromosome damage. DHAQ was also more genotoxic than Adriamycin. In cytogenetic assays, the activities of all drugs were reduced to different degrees in the presence of a S-9 metabolic system. Dis as revealed by cytogenetic assays; i.e., the drug with the highest therapeutic activity (DHAQ) was most active in inducing chromosome damage. DHAQ was also more genotoxic than Adriamycin. In cytogenetic assays, the activities of all drugs were reduced to different degrees in the presence of a S-9 metabolic system. Discrepancies were observed between results obtained from cytogenic assays and those from mutagenesis assays. Whereas DHAQ was most active in cytogenetic studies, Adriamycin was most mutagenic or toxic. HAQ was least active cytogenetically, and this activity was not changed appreciably in the presence of metabolic enzymes. However, it was metabolically activated to a bacterial mutagen. Our studies suggest that the cytogenetic and mutagenesis assays may be sensitive to the activities of different agents and of different moieties of the same agent. The application of short-term in vitro assays to identify the chemical structures responsible for genetic toxicity and for therapeutic activities in vivo may lead to the better understanding of drug activities and to the development of more effective drugs.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Au WW,Butler MA,Matney TS,Loo TLsubject
Has Abstractpub_date
1981-02-01 00:00:00pages
376-9issue
2eissn
0008-5472issn
1538-7445journal_volume
41pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Gene-targeted mice that contain a His6-tagged mouse c-Myc cDNA, Myc(His), inserted head to head into different sites of the mouse immunoglobulin heavy-chain locus, Igh, mimic the chromosomal T(12;15)(Igh-Myc) translocation that results in the activation of Myc in the great majority of mouse plasmacytomas. Mice carryin...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1222
更新日期:2005-09-01 00:00:00
abstract::Tumor hypoxia induces the up-regulation of a gene program associated with angiogenesis, glycolysis, adaptation to pH, and apoptosis via the hypoxia-inducible transcription factors (Hifs) 1 and 2. Disruption of this pathway has been proposed as a cancer therapy. Here, we use short interfering RNAs to compare specific i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract::Twenty-four patients suspected of having ovarian carcinoma received i.v. injection with a combination of radiolabeled intact IgG (1 mg) and F(ab')2 fragments (1 mg) of the chimeric monoclonal antibody MOv18, each form labeled with 1.85 MBq 131I or 125I. Laparotomy was performed either 2 or 6 days after injection, and ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-11-15 00:00:00
abstract::Nitromidazole and nitrofuran derivatives comprise a large family of compounds, some of which have been shown to be hypoxic cell specific radiosensitizers in vivo and in vitro. The effects of metronidazole (2-methyl-5-nitroimidazole-1-ethanol) and nitrofurazone (5-nitro-2-furaldehyde semicarbazone) were studied on cell...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-03-01 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::CD38 is a leukocyte differentiation antigen that has been thought to be a phenotypic marker of different subpopulations of T- and B-lymphocytes. In myeloid cells, CD38 is expressed during early stages of differentiation. Virtually no information is available on regulation and functions of CD38. Recently we reported th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::Four hundred and forty-seven human tumor specimens were accessioned and processed for clonogenic assay, yielding 374 specimens, representing 23 different histiotypes, adequate for culture. Different levels of viable cell inoculum density produced contrasting effects between 255 solid tumors as compared to 72 malignant...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-07-15 00:00:00
abstract::VEGF/vascular permeability factor (VEGF/VPF or VEGF-A) is a pivotal driver of cancer angiogenesis that is a central therapeutic target in the treatment of malignancy. However, little work has been devoted to investigating functions of VEGF that are independent of its proangiogenic activity. Here, we report that VEGF p...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-4058
更新日期:2012-08-15 00:00:00
abstract::Acute myeloid leukemia (AML) is a heterogeneous clonal disorder with a poor clinical outcome. Previously, we showed that overproduction of reactive oxygen species (ROS), arising from constitutive activation of NOX2 oxidase, occurs in >60% of patients with AML and that ROS production promotes proliferation of AML cells...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-1920
更新日期:2020-03-01 00:00:00
abstract::Lectin binding [concanavalin A, biotinylated ricinus communis agglutinin, and biotinylated succinylated wheat germ agglutinin (B-SWGA)] was used to detect the glycosylated proteins associated with a residual protein fraction [insoluble in 4% sodium dodecyl sulfate and termed the nuclear residual fraction (NRF)] or wit...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract::Using computerized pharmacy records from 1969 to 1973 for a cohort of 143,574 members of the Kaiser Permanente Medical Care Program, we have been testing associations of 215 drugs or drug groups with subsequent incidence of cancer at 56 sites. This paper presents findings with follow-up through 1984. There were 227 st...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-10-15 00:00:00
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::We have used a structure-activity approach to investigate whether the Vinca alkaloids inhibit cell proliferation primarily by means of their effects on mitotic spindle microtubules or by another mechanism or by a combination of mechanisms. Five Vinca alkaloids were used to investigate the relationship in HeLa cells be...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-04-15 00:00:00
abstract::The inhibitor of caspase-3-activated DNase (ICAD) is a caspase-3 substrate that controls nuclear apoptosis. ICAD has two isoforms: a functional isoform of M(r) 45,000, ICAD-L/DNA fragmentation factor (DFF) 45; and a M(r) 35,000 isoform, ICAD-S/DFF35. ICAD-deficient murine cells display resistance to apoptotic stimuli ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00
abstract::Cancer stem-like cells (CSC) in hepatocellular carcinoma (HCC) are thought to mediate therapeutic resistance and poor survival outcomes, but their intrinsic and extrinsic control is not well understood. In this study, we found that the chromatin modification factor LSD1 is highly expressed in HCC CSC where it decrease...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-1236
更新日期:2018-02-15 00:00:00
abstract::We searched for potential suppressors of tumor metastasis by identifying the genes that are frequently down-regulated in hepatocellular carcinomas (HCC) while being negatively correlated with clinical parameters relevant to tumor metastasis, and we report here on the identification of N-myc downstream regulated gene 2...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-5040
更新日期:2008-06-01 00:00:00
abstract::Genome-wide association studies (GWAS) of bladder cancer have identified a number of susceptibility loci in European populations but have yet to uncover the genetic determinants underlying bladder cancer incidence among other ethnicities. Therefore, we performed the first GWAS in a Chinese cohort comprising 3,406 case...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-2564
更新日期:2016-06-01 00:00:00
abstract::Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the Text Information Extraction System (TIES) Cancer...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-15-1973
更新日期:2015-12-15 00:00:00
abstract::DNA index and S-phase fraction of 490 primary breast carcinomas were measured by flow cytometry, using paraffin-embedded tissue as a starting point. All patients had involvement of axillary lymph nodes and all were randomized onto one of the Ludwig Breast Cancer Trials I-IV between July 1978 and August 1981. The prese...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-09-01 00:00:00
abstract::HeLa cells were synchronized at the G1-S boundary by double thymidine block and treated for 1 hr with varying concentrations of the antibiotic anticancer protein neocarzinostatin (NCS). Cells were then released from the block and allowed to resume their cycle. Aliquots were removed at various times in order to monitor...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-07-01 00:00:00
abstract::The effect of retinoic acid (RA) on N-methyl-N'-nitro-N-nitrosoguanidine-induced transformation of primary cultures of rat tracheal epithelial cells was investigated. RA inhibited transformation of rat tracheal epithelial cells by up to 95% at concentrations of 3.3 to 33 nM which did not substantially affect cell surv...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-12-01 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::The alternative reading frame (ARF) tumor suppressor mediates growth arrest or apoptosis through activation of the p53 tumor suppressor. A prevailing concept is that ARF uses p21Cip1/Waf1, a p53-responsive gene and cyclin-dependent kinase (Cdk) inhibitor, to block cell cycle progression. Using p21 nullizygous cells, w...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-04-01 00:00:00
abstract::Altered DNA methylation is a key feature of cancer, and aberrant methylation is important in nasopharyngeal carcinoma (NPC) development. However, the methylation mechanisms underlying metastasis of NPC remain unclear. Analyzing data from public databases and conducting our own experiments, we report here that promoter...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-1754
更新日期:2019-02-15 00:00:00
abstract::Radiolabeled first-generation anti-tumor-associated glycoprotein-72 (TAG-72) monoclonal antibody (MAb), B72.3, has proven useful in detecting primary and secondary colorectal carcinoma. It has been anticipated that the development of second-generation, higher affinity, anti-TAG-72 MAbs, CC49 and CC83, would be of grea...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-01-15 00:00:00
abstract::The molecular mechanisms by which human cancer cells spread to bone are largely unexplored. The process likely involves cell adhesion molecules (CAMs) that are responsible for homophilic and heterophilic cell-cell interactions. One relevant CAM may be the calcium-dependent transmembrane glycoprotein E-cadherin. To inv...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::Glutamine supplementation has been advocated for patients requiring parenteral nutritional support. However, the direct effect of glutamine on neoplastic cells is poorly understood. We therefore investigated the effects of glutamine on the proliferation, differentiation, and cell-matrix interactions of two human colon...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-11-15 00:00:00
abstract::We previously reported (J. Galivan et al., Proc. Natl. Acad. Sci. USA, 82: 2598-2602, 1985) the synthesis and characterization of DL-erythro,threo-gamma-fluoromethotrexate (FMTX). The individual diastereomers, DL-erythro-FMTX (eFMTX) and DL-threo-FMTX (tFMTX), and their radiolabeled counterparts have now been prepared...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-08-15 00:00:00
abstract::The relative effectiveness of either sodium selenite or selenomethionine in the inhibition of mammary carcinogenesis was studied in virgin female Sprague-Dawley rats. In one experiment, rats were given 50 mg of 1-methyl-1-nitrosourea per kg of body weight s.c. at 50 days of age. Beginning 7 days post-1-methyl-1-nitros...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-07-01 00:00:00
abstract::Renal cell carcinoma is frequently infiltrated by cells of the immune system. This makes it important to understand interactions between cancer cells and immune cells so they can be manipulated to bring clinical benefit. Here, we analyze subsets and functions of T lymphocytes infiltrating renal cell tumors directly ex...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-0852
更新日期:2009-11-01 00:00:00