Abstract:
:Therapeutic strategies targeting DNA repair pathway defects have been widely explored, but often only benefit small numbers of patients. Here we characterized potential predictive biomarkers for treatment with AsiDNA, a novel first-in-class DNA repair inhibitor. We evaluated genetic instability and DNA repair defects by direct and indirect assays in 12 breast cancer cell lines to estimate the spontaneous occurrence of single-strand and double-strand breaks (DSB). For each cell line, we monitored constitutive PARP activation, spontaneous DNA damage by alkaline comet assay, basal micronuclei levels, the number of large-scale chromosomal rearrangements (LST), and the status of several DNA repair pathways by transcriptome and genome analysis. Sensitivity to AsiDNA was associated with a high spontaneous frequency of cells with micronuclei and LST and specific alterations in DNA repair pathways that essentially monitor DSB repair defects. A high basal level of micronuclei as a predictive biomarker for AsiDNA treatment was validated in 43 tumor cell lines from various tissues and 15 models of cell- and patient-derived xenografts. Micronuclei quantification was also possible in patient biopsies. Overall, this study identified genetic instability as a predictive biomarker for sensitivity to AsiDNA treatment. That micronuclei frequency can be measured in biopsies and does not reveal the same genetic instability as conventional genome assays opens new perspectives for refining the classification of tumors with genetic instability. Cancer Res; 77(16); 4207-16. ©2017 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Jdey W,Thierry S,Popova T,Stern MH,Dutreix Mdoi
10.1158/0008-5472.CAN-16-2693subject
Has Abstractpub_date
2017-08-15 00:00:00pages
4207-4216issue
16eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-16-2693journal_volume
77pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::The pool sizes of purine nucleotides, nucleosides, and nucleobases were measured in the host tissues liver, skeletal muscle, and blood of Ehrlich ascites tumor-bearing mice during the different periods of tumor growth. There were large differences of tissue concentrations of these metabolites between control animals, ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
abstract::A series of mouse mammary tumor subpopulation lines were compared for growth properties and sensitivity to chemotherapeutic drugs when grown as boluses in a collagen gel matrix versus in monolayer culture. Although the cell lines exhibited characteristic rates of bolus expansion in collagen, this growth was not parall...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-09-01 00:00:00
abstract::The effects of a combination of simvastatin, a cholesterol-lowering agent, and carmustine (BCNU; N,N'-bis(2-chloroethyl)-N-nitrosourea) on experimental C6 glioma were studied in vitro and in vivo. In vitro simvastatin and BCNU alone inhibited cell proliferation in a dose-dependent fashion. A subliminal concentration o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::A number of studies in bacteria have indicated that deoxythymidine 5'-triphosphate may be a repressor or corepressor of ribonucleotide reductase. For determination of whether a similar regulating mechanism exists in mammalian cells, HeLa cells and partially hepatectomized rats were treated with either methotrexate, 5-...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-12-01 00:00:00
abstract::Type 2 diabetes, which is mainly linked to obesity, is associated with increased incidence of liver cancer. We have previously found that in various models of obesity/diabetes, hyperinsulinemia maintains heightened hepatic expression of cyclin D1, suggesting a plausible mechanism linking diabetes and liver cancer prog...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-0106
更新日期:2020-08-15 00:00:00
abstract::Hematoporphyrin [1,3,5,8-tetramethyl-2,4-bis(hydroxyethyl)-porphin-6,7-dipropio nic acid dihydrochloride derivative] (HPD) is a compound that was studied in a number of laboratories because of its cytocidal activity after activation by light. Modification of immune function seen during the photochemotherapeutic studie...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-04-01 00:00:00
abstract::Recent studies have revealed that procaspase-8 has an important function in cell adhesion and motility. Src phosphorylation controls this function by preventing the conversion of procaspase-8, which is an adhesion/migration factor, to mature caspase-8, which is an apoptosis-inducing factor. This provides a mechanism t...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-08-0952
更新日期:2008-06-15 00:00:00
abstract::In vitro maturation was induced with 12-O-tetradecanoylphorbol-13-acetate in leukemic cell samples from patients with chronic lymphocytic leukemia (n = 10) and prolymphocytic leukemia (n = 4). The cells were studied for morphology, for immunological markers using the fluorescence activated cell sorter, and for acid ph...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-04-01 00:00:00
abstract::The role of the insulin-like growth factor I receptor (IGF-IR) in programmed cell death has been investigated in vivo in a biodiffusion chamber, where the extent of cell death could be determined quantitatively. We found that a decrease in the number of IGF-IRs causes massive apoptosis in vivo in several transplantabl...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract::The rapidly expanding understanding of the progressive processes of carcinogenesis provides opportunities for the identification of molecular biological markers reflecting events from exposure through clinical disease. These molecular biological markers can be classified into categories of markers of exposure reflecti...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:
更新日期:1994-04-01 00:00:00
abstract::Translocation of the bcl-2 gene to the immunoglobulin heavy chain gene is the most common alteration in follicular lymphoma. The result is the deregulated expression of bcl-2 and increased resistance to cell death. Regulation of the immunoglobulin heavy chain gene is controlled in part by four DNase I-hypersensitive r...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-10-15 00:00:00
abstract::To evaluate the role of the human T-cell-specific tyrosine kinase lck (YT16), we measured the levels of lck expression in thymocytes, peripheral T-cells, and leukemia T-cell lines which are arrested at different stages of thymic differentiation. The results indicate that higher levels of the lck message can be found i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-02-15 00:00:00
abstract::Methylation associated inactivation of RASSF1, a putative tumor suppressor identified at 3p21.3, has been frequently observed in several human malignancies, including lung and breast cancers. To explore the penetrance of RASSF1 in gastric carcinogenesis, we performed expression and mutation analyses of 3 isotypes of R...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
abstract::The clinically relevant polyamine analogue N(1),N(11)-diethylnorspermine (DENSPM) inhibits cell growth by down-regulating polyamine biosynthesis, up-regulating polyamine catabolism at the level of spermidine/spermine N(1)-acetyltransferase (SSAT), and depleting intracellular polyamine pools. Among human melanoma cell ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00
abstract::We are developing a noninvasive approach for targeting imaging and therapeutic radionuclides to prostate cancer. Our method, Enzyme-Mediated Cancer Imaging and Therapy (EMCIT), aims to use enzyme-dependent, site-specific, in vivo precipitation of a radioactive molecule within the extracellular space of solid tumors. A...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3309
更新日期:2007-03-01 00:00:00
abstract::Activated beta-catenin regulates the transcription of oncogenic target genes and is critical for tumorigenesis. Because nuclear functions are frequently coupled, we investigated whether it also has a role in alternative splicing of oncogenic genes. We showed that stabilized beta-catenin caused alternative splicing of ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-2526
更新日期:2006-11-01 00:00:00
abstract::Breast cancer has been redefined into three clinically relevant subclasses: (i) estrogen/progesterone receptor positive (ER+/PR+), (ii) HER2/ERRB2 positive, and (iii) those lacking expression of all three markers (triple negative or basal-like). While targeted therapies for ER+/PR+ and HER2+ tumors have revolutionized...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-1098
更新日期:2012-11-15 00:00:00
abstract::Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47-68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genotype of c...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-1982
更新日期:2004-02-01 00:00:00
abstract::Glioblastoma is the most aggressive primary brain tumor and responds poorly to currently available therapies. Transcriptomic characterization of glioblastoma has identified distinct molecular subtypes of glioblastoma. Gain-of-function alterations leading to enhanced platelet-derived growth factor (PDGF) signaling are ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-2157
更新日期:2016-05-15 00:00:00
abstract::In order to elucidate the response of mitochondria to the increase in cellular energy demand after hepatectomy, we have examined the effects of partial hepatectomy and hepatic artery ligation on the energy-transducing system of rat liver mitochondria. Specific content of DNA in the mitochondria increased on the first ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) levels are dramatically increased in human keratinocytes (HKc) immortalized with full-length human papillomavirus type 16 (HPV16) DNA (HKc/HPV16), but increases in EGFR levels actually precede immortalization. In some normal HKc strains, acute expression of HPV16 E6 (but not HPV...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-05-01 00:00:00
abstract::Two commonly occurring genetic aberrations of human prostate cancer [i.e., overexpression of a mitogenic polypeptide (fibroblast growth factor 8, isoform b or FGF8b) and loss of function of PTEN tumor suppressor] were recapitulated into a new combinatorial mouse model. This model harboring the Fgf8b transgene and hapl...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-3440
更新日期:2006-02-15 00:00:00
abstract::Procarbazine, a chemotherapeutic hydrazine, is thought to be metabolized to an alkylating species similar to methyl carbonium ion by multistep reactions involving cytochrome P-450, monoamine oxidase, and cytosolic enzymes. The DNA-damaging and cytotoxic potential of procarbazine and its metabolites in murine L1210 leu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::Oncogene activation and loss of tumor suppressor function changes the metabolic activity of cancer cells to drive unrestricted proliferation. Moreover, cancer cells adapt their metabolism to sustain growth and survival when access to oxygen and nutrients is restricted, such as in poorly vascularized tumor areas. We sh...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-0650
更新日期:2020-01-15 00:00:00
abstract::Despite significant advances in cancer precision medicine, a significant hurdle to its broader adoption remains the multitude of variants of unknown significance identified by clinical tumor sequencing and the lack of biologically validated methods to distinguish between functional and benign variants. Here we used fu...
journal_title:Cancer research
pub_type: 评论,杂志文章
doi:10.1158/0008-5472.CAN-20-0865
更新日期:2020-10-01 00:00:00
abstract::The efficiency of tumor induction by oncogenes is influenced by modifier genes that determine individual susceptibility. We have used a transgenic mouse model to examine the role of a candidate susceptibility gene, bcl-2, for development of Raf oncogene-induced lung adenomas. Loss of bcl-2 greatly retarded tumor devel...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-11-01 00:00:00
abstract::Anti-idiotype monoclonal antibodies (Mabs) to mLL2, an anti-B-cell lymphoma and CD22-specific murine IgG2a-kappa Mab, were generated by hybridoma technology from splenocytes of Copenhagen rats immunized with mLL2 F(ab')2. Mab WN, an IgG2a-kappa, was selected based on its specific binding to mLL2 and not other IgG isot...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::The present work is a continuation of our studies to improve the graft versus leukemia (GVL) effect in autologous bone marrow transplantation. We have recently shown that the GVL effect of bone marrow transplantation (BMT) with interleukin 2 (IL-2)-activated bone marrow (ABM) followed by IL-2 therapy immediately after...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-04-15 00:00:00
abstract::The growth inhibitory effects of combinations of antifolates on hepatoma cells in culture have been examined. In these studies methotrexate or the lipophilic inhibitors of dihydrofolate reductase were used with the thymidylate synthase inhibitor N10-propargyl-5,8-dideazafolate (PDDF). Under certain conditions partial ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-10-15 00:00:00
abstract::In order to further understand the role of the host organ in tumor progression, we have transplanted into nude mice histologically intact human colon cancer tissue on the serosal layers of the stomach (heterotopic site) and the serosal layers of the colon (orthotopic site). Xenograft lines Co-3, which is well differen...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00