Abstract:
:Cloned lines of Adriamycin (ADR)-sensitive and -resistant P388 leukemia have been established from single cell cultures. A marker chromosome M1 was found in all cells in the heterogeneous resistant P388/ADR parental line as well as in the cloned resistant lines P388/ADR/3 and P388/ADR/7; a different marker chromosome M2 was present in the heterogeneous sensitive P388 parental line as well as the cloned sensitive line P388/4. Dose-survival studies showed that D0, the dose of Adriamycin reducing survival to 1/e (i.e., 37% of the initial population), was 33 +/- 5 (SE) nM for sensitive P388/4 cells, 169 +/- 17 nM for resistant P388/ADR/3 cells, and 336 +/- 28 nM for the more resistant P388/ADR/7 cells. Drug uptake in sensitive P388/4 cells was 1.6-fold greater than in resistant P388/ADR/3 cells and 2.1-fold greater than in resistant P388/ADR/7 cells. The number of DNA single-strand breaks produced per microM Adriamycin was 131 +/- 9 rad equivalents in sensitive clone 4 cells, 41 +/- 8 rad equivalents in resistant clone 3 cells, and 33 +/- 11 rad equivalents in resistant clone 7 cells. The number of DNA double-strand breaks per microM Adriamycin was 1721 +/- 126 rad equivalents in sensitive cells, 117 +/- 36 rad equivalents in resistant P388/ADR/3 cells, and 194 +/- 16 rad equivalents in resistant P388/ADR/7 cells. Differences in drug uptake were insufficient to explain the higher incidence of DNA single- and double-strand breaks in sensitive cells. These findings strongly support the concept that resistance to Adriamycin in P388 leukemia cells is multifactorial; however, this study did not resolve whether these changes arise from a single pleiotropic mutation or from multiple mutations. In sensitive P388/4 cells the number of DNA single-strand breaks formed could all be attributed to double-strand breaks. However, in both resistant cell lines the level of induction of single-strand breaks was in excess of that due to double-strand breaks, and this excess of single-strand breaks appeared to vary directly with the degree of resistance, being greater in the more resistant clone 7 cells than in the less resistant clone 3 cells. In both sensitive and resistant cell lines the ratio of true single- to double-strand breaks varied inversely with the concentration of Adriamycin. Finally, the cytotoxic activity of Adriamycin appeared to correlate more closely with formation of DNA double-strand breaks than with single-strand lesions.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Goldenberg GJ,Wang H,Blair GWsubject
Has Abstractpub_date
1986-06-01 00:00:00pages
2978-83issue
6eissn
0008-5472issn
1538-7445journal_volume
46pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Sulindac is the most extensively investigated clinically relevant chemopreventive nonsteroidal anti-inflammatory drug. Sulindac sulfide is one of the major metabolites of sulindac that is believed to mediate its antitumorigenic effects by inducing apoptosis. Recent evidence suggests that sulindac sulfide engages the m...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-09-15 00:00:00
abstract::Colorectal cancers with widespread CpG island methylation display a number of distinct clinicopathological features, and it has been suggested that the condition has an inheritable genetic component. To address this possibility, histories of cancer were obtained from 562 individuals undergoing curative surgery for uns...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-03-3978
更新日期:2004-10-15 00:00:00
abstract::verapamil, a calcium-influx blocker, enhanced the cytotoxicity of vincristine (VCR) in vitro 6- to 12-fold in eight human hemopoietic tumor cell lines established from acute lymphatic leukemia, acute myelogenous leukemia, and Burkitt's lymphoma. Great enhancement of VCR cytotoxicity was obtained in a VCR-resistant sub...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-05-01 00:00:00
abstract::Measurement of pH in tissue has shown that the microenvironment in tumors is generally more acidic than in normal tissues. Major mechanisms which lead to tumor acidity probably include the production of lactic acid and hydrolysis of ATP in hypoxic regions of tumors. Further reduction in pH may be achieved in some tumo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-08-15 00:00:00
abstract::A complementary DNA (cDNA) clone (B4) encoding the catalytic subunit of a cAMP-dependent protein kinase (PKAc) was isolated from a lambda gt10 rat brain cDNA library, using a synthetic oligonucleotide probe whose sequence was based on the known amino acid sequence of a bovine cardiac PKAc. Sequence analysis of this cl...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-03-15 00:00:00
abstract::A simple method is described for quantitating pulmonary metastases in C57BL/6J mice implanted with the Lewis T241 fibrosarcoma. Lungs were removed from tumor-bearing mice, homogenized, and diluted to 14 ml with supplemented Roswell Park Memorial Institute Tissue Culture Medium 1640 (+5% fetal calf serum). Twenty-five ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-12-01 00:00:00
abstract::Dietary genistein, a natural flavone compound found in soy, has been proposed to be responsible for the low rate of breast cancer in Asian women. The cellular mechanisms of genistein's chemopreventive effects in vio have been largely unexplored. In our previous studies, we found that genistein exerted pronounced antip...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-11-01 00:00:00
abstract::Ascites tumor cells can be cultivated at a reduced serum concentration if cholesterol (2.50 mg per 100 ml of medium) is added to the culture medium. At serum concentrations of 3%, optimal growth properties are obtained; below 3%, cell cultures usually perish after a few days. Cells grown in the presence of added chole...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-06-01 00:00:00
abstract::Emerging technologies allow broad profiling of the cancer genome for differential DNA methylation relative to benign cells. Herein, bisulfite-modified DNA from lymph nodes with either reactive hyperplasia or follicular lymphoma (FL) were analyzed using a commercial C/UpG genotyping assay. Two hundred fifty-nine differ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-2984
更新日期:2009-02-01 00:00:00
abstract::The hepatocarcinogen safrole is metabolized both to 1'-hydroxysafrole, a proximate hepatocarcinogen, and to 1'-oxosafrole, which is electrophilic but has little or no carcinogenic activity in rats and mice. As a part of a study on the metabolic interrelationships of these metabolites, their biliary and urinary conjuga...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-08-01 00:00:00
abstract::The effects of various forms of tocopherol (vitamin E) on the growth and differentiation of mouse melanoma (B-16) and mouse fibroblast (L-cells) cells in culture were studied. D-alpha-tocopherol acid succinate induced morphological alterations and growth inhibition in melanoma cells. When vitamin E acid succinate was ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-02-01 00:00:00
abstract::Based on reports that both human and murine lymphoblastoid cell lines can effect lysis in antibody-dependent (ADCC) and mitogen-induced (MICC) cell-mediated cytotoxicity, 10 human lymphoblastoid cell lines were investigated for their ability to act as effector cells in these lytic reactions. Four cell lines promoted M...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-11-01 00:00:00
abstract::Busulfan, a bifunctional alkylating agent, is a mainstay of myeloablative preparative regimens before hematopoietic stem cell transplantation. The apparent oral clearance of busulfan expressed relative to body surface area is 2-3-fold higher in children 1-4 years old than it is in adults. The first step in busulfan el...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-12-15 00:00:00
abstract::Cytogenetic analysis has indicated that deletion of chromosome 9p occurs in a significant number of non-small cell lung and mesothelioma tumors. Using paired oligonucleotide primers, we have undertaken an extensive analysis of 9p markers to determine homozygous and heterozygous loss of marker sequences. Homozygous los...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::Somatic copy number variations (CNV) may drive cancer progression through both coding and noncoding transcripts. However, noncoding transcripts resulting from CNV are largely unknown, especially for circular RNAs. By integrating bioinformatics analyses of alerted circRNAs and focal CNV in lung adenocarcinoma, we ident...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-2808
更新日期:2018-06-01 00:00:00
abstract::Anti-inflammatory drugs and antibiotics alter the risk of breast cancer in women, but roles for bacteria and inflammation in breast malignancies are poorly understood. A recent study in mice suggests that intestinal bacteria can trigger mammary carcinoma. The mechanisms involved in this effect suggest that dysregulate...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-06-3468
更新日期:2007-02-01 00:00:00
abstract::The lipid hydrolase enzyme acid sphingomyelinase (ASM) is required for the conversion of the lipid cell membrane component sphingomyelin into ceramide. In cancer cells, ASM-mediated ceramide production is important for apoptosis, cell proliferation, and immune modulation, highlighting ASM as a potential multimodal the...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-3313
更新日期:2017-11-01 00:00:00
abstract::Metastatic prostate cancer continues to pose a difficult therapeutic challenge. Prostate cancer progression is associated with aberrant O-glycosylation of cancer cell surface receptors, but the functional impact of such events is uncertain. Here we report spontaneous metastasis of human prostate cancer xenografts that...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-0641
更新日期:2016-10-01 00:00:00
abstract::A monoclonal antibody (IgG1) has been prepared that specifically detects Chinese hamster ovary cells expressing a multidrug-resistant phenotype. This antibody recognizes the membrane P-glycoprotein (Mr 170,000) associated with drug resistance as determined by enzyme-linked immunosorbent assay with purified P-glycoprot...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract::The interaction between platelets and tumor cells is important in the formation of pulmonary metastasis. We previously established the 8F11 monoclonal antibody (mAb) by immunizing rats with the NL-17 cell line, a highly metastatic variant of mouse colon adenocarcinoma 26. 8F11 could inhibit the platelet aggregation in...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-07-15 00:00:00
abstract::New sublines of Chinese hamster CHL cells stably expressing human NAT1 or NAT2 N-acetyltransferases or O-acetyltransferase of Salmonella typhimurium were established, and their sensitivities to carcinogenic nitroarenes and aromatic amines were compared using the in vitro micronucleus test. The subline expressing human...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::Overexpression of PRL-3, an oncogenic phosphatase, was identified as a novel cluster in patients with newly diagnosed multiple myeloma. However, the regulation and oncogenic activities of PRL-3 in multiple myeloma warrant further investigation. Here, we report that IL6 activates STAT3, which acts as a direct transcrip...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-0343
更新日期:2019-09-15 00:00:00
abstract::This study was initiated with the objective of separating and characterizing two or more nuclear subfractions, which could then be compared with respect to their relative propensity for binding carcinogenic polycyclic aromatic hydrocarbons. Nuclei were isolated from cloned AKR-2B mouse embryo cells, which are suscepti...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-08-01 00:00:00
abstract::Metabolic reprogramming is a hallmark of cancer that includes increased glucose uptake and accelerated aerobic glycolysis. This phenotype is required to fulfill anabolic demands associated with aberrant cell proliferation and is often mediated by oncogenic drivers such as activated BRAF. In this study, we show that th...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-2215
更新日期:2018-05-01 00:00:00
abstract::The breast cancer susceptibility gene BRCA2 is expressed in a wide range of tissues as an 11-kb mRNA transcript encoding a 3418-amino acid protein, which is involved in the response to DNA damage. To obtain a better molecular characterization of BRCA2 expression in breast tissue, we analyzed full-length BRCA2 mRNA by ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-06-01 00:00:00
abstract::Combining microtubule-targeting antimitotic drugs with targeted apoptosis potentiators is a promising new chemotherapeutic strategy to treat cancer. In this study, we investigate the cellular mechanism by which navitoclax (previously called ABT-263), a Bcl-2 family inhibitor, potentiates apoptosis triggered by paclita...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-4336
更新日期:2011-07-01 00:00:00
abstract::Changes in binding of dexamethasone (9 alpha-fluoro-11 beta, 17 alpha, 21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione) to its receptors in regenerating rat liver after 70% hepatectomy were examined. Specific receptors for dexamethasone in the liver remnants of adrenalectomized rats decreased significantly du...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-12-01 00:00:00
abstract::Neurofibromatosis type 2 (NF2) is a dominantly inherited cancer disorder caused by mutations at the NF2 gene locus. Merlin, the protein product of the NF2 gene, has been shown to negatively regulate Rac1 signaling by inhibiting its downstream effector kinases, the p21-activated kinases (Pak). Given the implication of ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0866
更新日期:2008-10-01 00:00:00
abstract::Upon incubation of cultured mammalian cells with the new anthracycline analogues cyanomorpholinyldoxorubicin and morpholinyldoxorubicin, nucleoli irreversibly segregate into their substructures which form individual portions of the nucleolar mass and characteristic electron-dense components adjacent to the nucleolonem...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-07-15 00:00:00
abstract::We previously reported that intetumumab (CNTO 95), a fully human anti-αv integrin monoclonal antibody, is a radiosensitizer in mice with xenograft tumors. Because intetumumab does not cross-react with mouse integrins, but has cross-reactivity with rat integrins, we next studied the potential combined use of radiation ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-1639
更新日期:2010-10-01 00:00:00