Abstract:
:We have synthesized fluoromycin (FLM), a novel fluorescein-labeled derivative of talisomycin S10b (TLM S10b), and used it to evaluate cellular drug accumulation and distribution in bleomycin (BLM)-sensitive and -resistant cell lines. The fluorescence intensity of FLM was 300- to 400-fold greater than that of BLM A2, TLM S10b, or the lipophilic BLM analogue, liblomycin. FLM possessed an antiproliferative potency similar to liblomycin in BLM-sensitive human A-253 squamous carcinoma cells but was less potent than BLM A2 or TLM S10b. C-10E cells, a clone of A-253 cells with 40- to 50-fold resistance to BLM A2 and TLM S10b, were 50-fold resistant to FLM. A partially revertant cell population (C-10E ND) regained sensitivity to BLM A2, TLM S10b, and FLM. FLM like BLM cleaved pGEM-3Z plasmid DNA in vitro in a concentration-dependent manner. Flow cytometric analysis of FLM content in C-10E and C-10E ND cell lines showed 4-fold and 2-fold lower fluorescence intensity, respectively, compared with A-253 cells. Similar results were seen by fluorescence spectrophotometry with cell extracts. Fluorescence microscopy indicated heterogeneous distribution among A-253 cells with at least 50% of the cells exhibiting marked nuclear fluorescence localization. In contrast, C-10E cells displayed lower cellular fluorescence and predominantly cytoplasmic localization. C-10E ND cells exhibited a mixed population of nuclear and cytoplasmic vesicular localization with fluorescence levels that were intermediate between A-253 and C-10E cells. Thus, BLM-resistant cells have reduced levels of FLM and appear to have a lower nuclear:cytoplasmic ratio of FLM. FLM may be useful in studying the intracellular fate of BLM-like drugs as well as providing a tool to detect and isolate BLM-resistant cells.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Mistry JS,Jani JP,Morris G,Mujumdar RB,Reynolds IJ,Sebti SM,Lazo JSsubject
Has Abstractpub_date
1992-02-01 00:00:00pages
709-18issue
3eissn
0008-5472issn
1538-7445journal_volume
52pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Functional studies using freshly isolated tumor-infiltrating B lymphocytes(TIB) are difficult to perform and interpret. Here we document a novel function of TIB using fresh human lung cancer tissues engrafted in SCID mice; they are at activated state and produce tumor-specific antibodies in tumor microenvironment: (a)...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-03-15 00:00:00
abstract::Insulin-like growth factor (IGF) I has important growth regulatory functions in normal growth and development. IGF-I is also a mitogen for a number of cancer cell lines; however, its autocrine effect has not been well established. In this study, the expression of IGF-I, its receptor, and its major serum-binding protei...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-06-15 00:00:00
abstract::In this study of the role of microfloral beta-glucuronidase in colonic carcinogenesis, the effect of beta-glucuronidase inhibitor was evaluated. Starting at 5 weeks of age, male Donryu rats were fed either a semisynthetic diet or the same diet containing 0.1% beta-glucuronidase inhibitor as N-cyclohexyl-5-O-acetyl-2,4...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract::Highly metastatic and chemotherapy-resistant properties of malignant melanomas stand as challenging barriers to successful treatment; yet, the mechanisms responsible for their aggressive characteristics are not fully defined. We show that a distinct population expressing CD133 (Prominin-1), which is highly enriched af...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-2591
更新日期:2010-12-15 00:00:00
abstract::Hormone stimulation of responsive neoplasms is a potential strategy for improving the target selectivity of cancer chemotherapy. Using an alkaline DNA-unwinding technique to detect drug-induced DNA strand breakage, we have shown that estrogen stimulation of T-47D human breast cancer cells enhances induction of DNA cle...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-01-15 00:00:00
abstract::The epithelial-to-mesenchymal transition (EMT) is a reversible process comprised of various subprograms via which epithelial cells reduce their intercellular adhesions and proliferative capacity while gaining a mesenchymal phenotype with increased migratory and invasive properties. This process has been well described...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-17-0032
更新日期:2017-09-01 00:00:00
abstract::The protein composition of breast secretions from 99 premenopausal women with benign or malignant breast diseases and from 70 control women without breast pathologies has been studied by using polyacrylamide gel electrophoresis. These fluids have been classified into two types according to their major polypeptide comp...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::More than 35 different partner genes with the mixed lineage leukemia (MLL) gene have been cloned from leukemia cells with translocations involving chromosome 11 band q23. In this study, we report on a novel fusion partner of the MLL gene, AF4p12, which we have identified as the human homologue to the furry gene of Dro...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1325
更新日期:2005-08-01 00:00:00
abstract::Three loci have been implicated in the etiology of familial breast cancer; the BRCA1 locus on 17q, the p53 gene on 17p, and the androgen receptor gene on the X chromosome. However, it has been estimated that in approximately 50% of all breast cancer families the predisposing genetic defect is not linked to any of thes...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-09-15 00:00:00
abstract::The concept that different leukemias are developmentally distinct and, like in normal hematopoiesis, generated by restricted populations of cells named leukemia-initiating cells (LIC), is becoming more established. These cancer stem-like cells have been assumed to have unique properties, including the capability of se...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-20-2571
更新日期:2021-01-07 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::Emerging evidence indicates that gut microbiota affect the response to anticancer therapies by modulating the host immune system. In this study, we investigated the impact of the gut microbiota on immune-mediated trastuzumab antitumor efficacy in preclinical models of HER2-positive breast cancer (BC) and in 24 patient...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-1659
更新日期:2021-01-22 00:00:00
abstract::The effects of combined administration of cimetidine and tetragastrin on gastric acid secretion, the labeling index of the gastric mucosa, and the incidence of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in inbred Wistar rats. Prolonged administration of tetragastrin in de...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-03-15 00:00:00
abstract::L1210 murine leukemia cells were treated in vitro with the novel antineoplastic agent 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d] -1,2,3,5-tetrazin-4(3H)-one (M&B 39565), and its interaction with cellular DNA was assessed by alkaline elution. DNA interstrand cross-link and DNA-protein cross-link formation was quantifi...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract::H2AX phosphorylation is an early step in the response to DNA damage. It is widely accepted that ATM (ataxia telangiectasia mutated protein) phosphorylates H2AX in response to DNA double-strand breaks (DSBs). Whether DNA-dependent protein kinase (DNA-PK) plays any role in this response is unclear. Here, we show that H2...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-3207
更新日期:2004-04-01 00:00:00
abstract::Coho salmon (Oncorhynchus kisutch) and chinook salmon (Oncorhynchus tshawytscha) from Lakes Ontario, Michigan, Erie, or Huron were found to suffer epizootics of thyroid hyperplasia and goiters which appeared to have an environmental etiology. There were 13-fold differences in goiter prevalence within the Great Lakes, ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-06-01 00:00:00
abstract::Micropthalmia transcription factor (Mitf) is involved in melanocyte development and differentiation. The current study was undertaken to determine whether there is a relationship between Mitf expression and survival in patients with intermediate-thickness (1.0-4.0 mm) melanoma. Original paraffin blocks or slides of th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-09-15 00:00:00
abstract::Rat pheochromocytoma PC12 cells form tumors when placed into the brains of Sprague-Dawley rats under specific conditions. We now show that tumorigenic potential is regulated by the microenvironment of the developing cerebrum. PC12 cell aggregates were identified in the periventricular or intraventricular spaces within...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::We have examined the ability of ingenol to bind to and activate protein kinase C and to induce similar responses to the phorbol esters in biological systems. The rationale was that ingenol possesses the critical functionalities of the phorbol ester pharmacophore with the exception of the hydrophobic domain; it might t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::We evaluated primary lung cancers, tumor cell lines, and preneoplastic bronchial lesions for molecular genetic abnormalities in the candidate tumor suppressor gene FHIT, which spans the FRA3B fragile site at 3p14.2. 3p14.2 allele loss was very frequent in 32 lung cancer cell lines [100% of small cell lung cancer and 8...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-06-01 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::Organization of cancer cells into endothelial-like cell-lined structures to support neovascularization and to fuel solid tumors is a hallmark of progression and poor outcome. In triple-negative breast cancer (TNBC), PDGFRβ has been identified as a key player of this process and is considered a promising target for bre...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-0140
更新日期:2016-09-15 00:00:00
abstract::In this study, we identified 53 aberrantly hypermethylated DNA sequences in adult T-cell leukemia (ATL) cells using methylated CpG island amplification/representational difference analysis method. We also observed a proportionate increase in the methylation density of these regions with disease progression. Seven gene...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-1422
更新日期:2004-09-01 00:00:00
abstract::Human bronchial carcinoma is thought to develop through progressive stages from basal cell hyperplasia to squamous metaplasia, dysplasia, carcinoma in situ, and finally invasive cancer. In this study, we used tissue microdissection to examine loss of heterozygosity of chromosomes 3p21, 5q21, and 9p21 at each stage of ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-11-15 00:00:00
abstract::The selective pressures leading to cancers with mutations in both KRAS and PIK3CA are unclear. Here, we show that somatic cell knockin of both KRAS G12V and oncogenic PIK3CA mutations in human breast epithelial cells results in cooperative activation of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protei...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-1578
更新日期:2013-06-01 00:00:00
abstract::ADAMs (a disintegrin and metalloproteinase) have important roles in development and diseases such as cancer. Previously, an ADAM15 splice variant (ADAM15B), which contains an inserted cytoplasmic Src-binding site, was linked to clinical aggressiveness in breast cancer, yet little was known about how this splice varian...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-4766
更新日期:2009-06-01 00:00:00
abstract::A sound rationale exists for antibody targeting of the MET receptor tyrosine kinase, but therapeutic agents that can broadly block HGF ligand binding and exon 14-mutated or amplified MET to induce receptor degradation have yet to be reported. Here we report the identification of several MET monoclonal antibodies (mAb)...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-0026
更新日期:2016-10-01 00:00:00
abstract::Reported estimates of ras mutation prevalence in lung adenocarcinoma of 15-24% may be underestimates because of the insensitivity of the assays used. We have devised a rapid, non-radioactive assay for ras mutations, which detects 1 mutant allele/10(3) normal alleles and have used it to study DNA isolated from 53 lung ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::We examined patterns of covalent modifications of DNA produced in rat liver after exposure to single and multiple doses of aflatoxin B1. The principal product, previously identified as 2,3-dihydro-3-hydroxy(N7-guanyl) aflatoxin B1, was removed rapidly from liver DNA in vivo after a 0.6-mg/kg dose was administered i.p....
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-01-01 00:00:00
abstract::Amino acid analysis of the culture medium was carried out in a human leukemic lymphoblastoid cell line (REH) established from the lymphoblasts of a patient with acute lymphoid leukemia. The results are compared with those of a reference cell line (LHN13) established from normal human lymphocytes. The most striking dif...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-11-01 00:00:00