Abstract:
:Cockayne syndrome (CS) patients are deficient in the transcription coupled repair (TCR) subpathway of nucleotide excision repair (NER) but in contrast to xeroderma pigmentosum patients, who have a defect in the global genome repair subpathway of NER, CS patients do not have an elevated cancer incidence. To determine to what extent a TCR deficiency affects carcinogen-induced mutagenesis and carcinogenesis, CS group B correcting gene (CSB)-deficient mice were treated with the genotoxic carcinogen benzo(a)pyrene (B[a]P) at an oral dose of 13 mg/kg body weight, three times a week. At different time points, mutant frequencies at the inactive lacZ gene (in spleen, liver, and lung) as well as at the active hypoxanthine phosphoribosyltransferase (Hprt) gene (in spleen) were determined to compare mutagenesis at inactive versus active genes. B[a]P treatment gave rise to increased mutant frequencies at lacZ in all of the organs tested without a significant difference between CSB-/- and wild-type mice, whereas B[a]P-induced Hprt mutant frequencies in splenic T-lymphocytes were significantly more enhanced in CSB-/- mice than in control mice. The sequence data obtained from Hprt mutants indicate that B[a]P adducts at guanine residues were preferentially removed from the transcribed strand of the Hprt gene in control mice but not in CSB-/- mice. On oral treatment with B[a]P, the tumor incidence increased in both wild-type and CSB-deficient animals. However, no differences in tumor rate were observed between TCR-deficient CSB-/- mice and wild-type mice, which is in line with the normal cancer susceptibility of CS patients. The mutagenic response at lacZ, in contrast to Hprt, correlated well with the cancer incidence in CSB-/- mice after B[a]P treatment, which suggests that mutations in the bulk of the DNA (inactive genes) are a better predictive marker for carcinogen-induced tumorigenesis than mutations in genes that are actively transcribed. Thus, the global genome repair pathway of NER appears to play an important role in the prevention of cancer.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Wijnhoven SW,Kool HJ,van Oostrom CT,Beems RB,Mullenders LH,van Zeeland AA,van der Horst GT,Vrieling H,van Steeg Hsubject
Has Abstractpub_date
2000-10-15 00:00:00pages
5681-7issue
20eissn
0008-5472issn
1538-7445journal_volume
60pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::The development of prophylactic cancer vaccines that protect healthy hosts from tumor development leaves open the question whether such vaccines are also effective against established tumors and metastases. We tested the therapeutic activity of a proven prophylactic anti-HER-2/neu vaccine against successive stages of ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-2499
更新日期:2007-11-15 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::Aberrant methylation patterns have long been known to exist in the promoter regions of key regulatory genes in the DNA of tumor cells. However, the mechanisms by which these methylation patterns become altered during the transformation of normal cells to tumor cells have remained elusive. We have recently shown in in ...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-07-0846
更新日期:2007-06-15 00:00:00
abstract::Oncogenic KRAS mutations occur frequently in lung adenocarcinoma. The signaling pathways activated by IL6 promote Kras-driven lung tumorigenesis, but the basis for this cooperation is uncertain. In this study, we used the gp130(F/F) (Il6st) knock-in mouse model to examine the pathogenic contribution of hyperactivation...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-2388
更新日期:2016-02-15 00:00:00
abstract::Methotrexate (MTX) is one of the most commonly used agents in the treatment of solid malignancies; however, the toxicities of MTX to bone marrow and gastrointestinal tract complicate this therapy. We, therefore, propose a gene-dependent enzyme prodrug therapy to limit these toxicities by localizing the production of M...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00
abstract::PTEN/MMAC1 is a major new tumor suppressor gene that encodes a dual-specificity phosphatase with sequence similarity to the cytoskeletal protein tensin. Recently, we reported that PTEN dephosphorylates focal adhesion kinase (FAK) and inhibits cell migration, spreading, and focal adhesion formation. Here, the effects o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-01-15 00:00:00
abstract::To identify CpG islands differentially methylated in pancreatic adenocarcinoma, we used methylated CpG island amplification (MCA) coupled with representational difference analysis. Of 42 CpG islands identified by MCA/representational difference analysis, 7 CpG islands [methylated in carcinoma of the pancreas (MICP)] w...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-12-01 00:00:00
abstract::We have recently identified a new gene, interleukin-17 receptor-like (IL-17RL), which is expressed in normal prostate and prostate cancer. This investigation is focused on the role of IL-17RL in prostate cancer. We found that IL-17RL was expressed at significantly higher levels in several androgen-independent prostate...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1130
更新日期:2006-01-01 00:00:00
abstract::CC-1065, a novel antibiotic produced by Streptomyces zelensis, was active against several experimental tumors in vivo and a broad spectrum of human tumor cells in vitro. This report describes its biological and biochemical effects of L1210 leukemia cells. CC-1065 is one of the most cytotoxic agents known. The concentr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::Members of the INK4 family of cyclin-dependent kinase (CDK) inhibitors specifically bind and inhibit the G1-specific CDK molecules CDK4 and CDK6. One of the INK4 molecules, p16, is also known as multiple tumor suppressor and has been found to be mutated or deleted in various tumors and cell lines. We have previously i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-02-01 00:00:00
abstract::MHC class I-restricted tumor antigen can be presented to CD8+ T cells by two distinct mechanisms. Direct presentation involves degradation of cytosolic proteins by the proteosome into peptides, transport of the peptides across the endoplasmic reticulum membrane, and expression of the MHC-peptide complex on the tumor c...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-02-01 00:00:00
abstract::Fatty acid synthase (FASN) is the terminal enzyme in de novo lipogenesis and plays a key role in cell proliferation. Pharmacologic inhibitors of FASN are being evaluated in clinical trials for treatment of cancer, obesity, and other diseases. Here, we report a previously unknown mechanism of FASN regulation involving ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-1597
更新日期:2016-12-01 00:00:00
abstract::A single i.p. injection of cyclophosphamide (CY), 15 mg/kg, was shown previously to be curative if administered to BALB/c mice 10 to 16 days post-MOPC-315 tumor inoculation when the tumors reached 20 to 25 mm (large tumors) but not if administered to mice four days post-tumor inoculation when their tumors were nonpalp...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-06-01 00:00:00
abstract::Radiation exposure is related to risk of numerous types of cancer, but relatively little is known about its effect on risk of multiple primary cancers. Using follow-up data through 2002 from 77,752 Japanese atomic bomb survivors, we identified 14,048 participants diagnosed with a first primary cancer, of whom 1,088 we...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-0276
更新日期:2010-09-15 00:00:00
abstract::Although apoptosis and necrosis are morphologically distinct manifestations of cell death, apoptosis and some necroses share common features in the death signaling pathway involving functional steps of death-driving interleukin 1beta-converting enzyme family proteases and anti-cell death protein Bcl-2. One evident phy...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-05-15 00:00:00
abstract::Destruction of cancer cells by cytotoxic T lymphocytes depends on immunogenic tumor peptides generated by proteasomes and presented by human leukocyte antigen (HLA) molecules. Functional differences arising from alleles of immunoproteasome subunits have not been recognized so far. We analyzed the genetic polymorphism ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-1883
更新日期:2011-12-01 00:00:00
abstract::A simple technique is described for fixing colony-containing layers of soft agar and drying them onto microscopic slides. The method is extrapolated from techniques used in immunology for permanent preservation of immunodiffusion or immunoelectrophoresis plates. Slides prepared in this fashion are eminently suitable f...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-03-01 00:00:00
abstract::Studies involving transcriptomics have revealed multiple molecular subtypes of hepatocellular carcinoma (HCC). Positron emission tomography/computed tomography (PET/CT) has also identified distinct molecular imaging subtypes, including those with increased and decreased choline metabolism as measured by the tissue upt...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-3837
更新日期:2019-04-01 00:00:00
abstract::By molecular genetic approach using polymorphic DNA markers which detect allelic deletion at specific chromosomal loci, we analyzed 30 human stomach cancers for possible loss of chromosomal heterozygosity. We analyzed 25 loci on 18 different chromosomes covering regions frequently deleted in several types of cancers. ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
abstract::Interleukin-2-based regimens of biological therapy have shown some clinical promise for the treatment of kidney cancer in humans, although the mechanisms responsible for tumor regression occurring in these patients remain unclear. Preclinical insight into these mechanisms is limited by a paucity of orthotopic animal m...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-08-15 00:00:00
abstract::A potent modifying locus of intestinal tumorigenesis in the mouse was recently identified as secretory phospholipase A2 (sPLA2). The human homologue of sPLA2 maps to chromosome 1p35, a region frequently lost in human tumors. To evaluate the possibility that sPLA2 was a tumor suppressor gene that was the target of the ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-11-15 00:00:00
abstract::Gliomas are primary brain tumors with high mortality and heterogeneous biology that is insufficiently understood. In this study, we performed a systematic analysis of the intrinsic organization of complex glioma transcriptome to gain deeper knowledge of the tumor biology. Gene coexpression relationships were explored ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-2465
更新日期:2010-12-15 00:00:00
abstract::In the present study, we examined the presence of deacetylases capable of producing free hexosamines, which we have shown earlier to be immunosuppressive against human natural killer (NK) cell-mediated cytotoxicity, from N-acetylhexosamines in human tumor cells. When human NK-resistant colon cancer cells (Colo-320DM) ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::Metabolite profiling using (1)H nuclear magnetic resonance (NMR) spectroscopy was used to investigate the metabolic changes associated with deletion of the gene for the transcriptional coactivator p300 in the human colon carcinoma cell line HCT116. Multivariate statistical methods were used to distinguish between meta...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-2999
更新日期:2006-08-01 00:00:00
abstract::Transforming growth factor (TGF)-beta is a potent regulator of many cell functions and a growth inhibitor for mammary epithelial cells. We now know of three highly homologous members of the human TGF-beta gene family. We have studied the expression of TGF-beta 1, -beta 2, and -beta 3 mRNA in four human breast cancer c...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-01-15 00:00:00
abstract::We have shown previously that the pathways leading to Fas-mediated apoptosis in prostatic carcinoma cell lines are intact, because apoptosis can be triggered either by Fas ligation alone in the Fas-sensitive cell lines PC3 and ALVA31 or by rendering the Fas-resistant cell lines DU145 and JCA1 Fas-sensitive by combined...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-04-15 00:00:00
abstract::Chronic exposure to the hepatocellular carcinogen diethylnitrosamine (DEN) causes a dose-dependent accumulation of the promutagenic DNA adduct O4-ethyldeoxythymidine in hepatocytes and increases in the number of initiated hepatocytes as indicated by gamma-glutamyl transpeptidase positive foci. Initiation is thought to...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-12-15 00:00:00
abstract::MTW9, a transplantable mammary tumor in Wistar Furth rats, shows little growth unless host serum prolactin is increased. This study compares the response to ovariectomy of MTW9-MtT, a tumor developed in rats bearing the mammosomatotropic tumor MtTW10 (serum prolactin 500 to 7000 ng/ml) with MTW9-P developed in rats gi...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-01-01 00:00:00
abstract::Fluorescent-labeled hormones can be used to study hormone-receptor interactions by means of fluorescence polarization, visualization by fluorescence microscopy, or separation methods, e.g., dextran-coated charcoal. Subcellular fragments, single cells, and tissue preparations are amenable to study; in this work rat ute...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-11-01 00:00:00
abstract::Squamous cell carcinoma (SCC) and keratoacanthoma (KA; SCC/KA) research has been hampered mainly by our lack of understanding the underlying genetic and epigenetic alterations associated with SCC/KA development, as well as the lack of animal models that faithfully recapitulate histopathologic features of human SCC/KA....
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-3274
更新日期:2016-11-15 00:00:00