Molecular analysis of the polymorphisms of thymidylate synthase on cell-free circulating DNA in blood of patients with advanced colorectal carcinoma.

Abstract:

:As a key enzyme in folate metabolism, the thymidylate synthase (TS) is important for the synthesis of nucleotides. Its polymorphisms may affect the TS gene expression and the susceptibility for Fluoropyrimidine (FU)-based chemotherapies. In this study, we assessed the relationship between the TS genotypes and clinical outcome to 5-FU-based chemotherapy, and examined whether cell-free circulating DNA is applicable for these molecular analyses. We combined the variable number tandem repeat (VNTR) and single nucleotide (SNP) polymorphisms of the TS promoter and the deletion variants (1494del6) in the 3'UTR with the occurrence of loss of heterozygosity (LOH) at the microsatellite markers D18S59, D18S1140, and D18S976 mapped up- and downstream to the TS locus. Cell-free blood DNA, tumor tissues, and leukocytes of 51 patients with advanced colorectal cancer were used. Genotyping revealed linkage disequilibrium between TS promoter and 3'UTR (p = 0.03) in blood and leukocytes. Inverse associations of the response to therapy with the number of polymorphisms (p = 0.05) and the 494del6 polymorphism (p < 0.02) were detected on serum DNA. The quantification of serum DNA showed significant correlations with the 1494del6 variant (p = 0.006) in tumor tissues and the combined polymorphisms in leukocytes (p < 0.04). In contrast to the low LOH frequency in blood, LOH spanned more than one marker in the primary tumor of the majority of the patients suggesting the loss of the entire TS locus. Our data provide insight into the molecular diversity of the regulation of the TS gene expression. This is the first study that compares multi-variant TS genotypes in different clinical specimens.

journal_name

Int J Cancer

authors

Schwarzenbach H,Goekkurt E,Pantel K,Aust DE,Stoehlmacher J

doi

10.1002/ijc.25096

subject

Has Abstract

pub_date

2010-08-15 00:00:00

pages

881-8

issue

4

eissn

0020-7136

issn

1097-0215

journal_volume

127

pub_type

杂志文章
  • Phenylbutyrate inhibits the invasive properties of prostate and breast cancer cell lines in the sea urchin embryo basement membrane invasion assay.

    abstract::Histone deacetylase inhibitors, such as phenylbutyrate, are currently undergoing clinical trials as potential anticancer agents. Phenylbutyrate can induce cell differentiation and apoptosis in a number of cancer cell types and can act in synergy with ionizing radiation and chemotherapy to induce apoptosis. We used the...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10609

    authors: Dyer ES,Paulsen MT,Markwart SM,Goh M,Livant DL,Ljungman M

    更新日期:2002-10-10 00:00:00

  • Prosurvival function of the granulin-epithelin precursor is important in tumor progression and chemoresponse.

    abstract::The granulin-epithelin precursor (GEP/PCDGF), a 68-88 kDa secreted glycoprotein, has been shown to be an important growth and survival factor for ovarian cancer cells. Furthermore, GEP expression is a predictor of patient survival in metastatic ovarian cancer cells. Up to this point, however, the molecular mechanisms ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22559

    authors: Pizarro GO,Zhou XC,Koch A,Gharib M,Raval S,Bible K,Jones MB

    更新日期:2007-06-01 00:00:00

  • Osteopontin expression in a group of lymph node negative breast cancer patients.

    abstract::The aim of this study was to examine the cellular distribution of osteopontin (OPN) protein [by immunohistochemical (IHC) analysis] and mRNA [by in situ hybridization (ISH)] in the primary tumors of lymph node negative (LNN) breast cancer patients and to determine whether the level of immunodetectable OPN may be assoc...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19981023)79:5<502::aid-ijc

    authors: Tuck AB,O'Malley FP,Singhal H,Harris JF,Tonkin KS,Kerkvliet N,Saad Z,Doig GS,Chambers AF

    更新日期:1998-10-23 00:00:00

  • Transactivation of MCP-1/CCL2 by beta-catenin/TCF-4 in human breast cancer cells.

    abstract::The loss of E-cadherin expression and the translocation of beta-catenin to the nucleus are frequently associated with the metastatic conversion of epithelial cells. In the nucleus, beta-catenin binds to the TCF/LEF-1 (T-cell factor/ lymphoid enhancer factor) transcription factor family resulting in the activation of s...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21291

    authors: Mestdagt M,Polette M,Buttice G,Noël A,Ueda A,Foidart JM,Gilles C

    更新日期:2006-01-01 00:00:00

  • Human BLCAP transcript: new editing events in normal and cancerous tissues.

    abstract::Bladder cancer-associated protein (BLCAP) is a highly conserved protein among species, and it is considered a novel candidate tumor suppressor gene originally identified from human bladder carcinoma. However, little is known about the regulation or the function of this protein. Here, we show that the human BLCAP trans...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25022

    authors: Galeano F,Leroy A,Rossetti C,Gromova I,Gautier P,Keegan LP,Massimi L,Di Rocco C,O'Connell MA,Gallo A

    更新日期:2010-07-01 00:00:00

  • Chromosome 15 trisomy in spontaneous and carcinogen-induced murine lymphomas of B-cell origin.

    abstract::G-banding analyses of 14 independently derived B-cell lymphomas showed the frequent occurrence of chromosome 15 trisomy. It was present in seven of nine spontaneous B-cell lymphomas, but in company with other trisomies, monosomies and marker chromosomes. In five carcinogen-induced primary B-cell leukemias, trisomy 15 ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910270109

    authors: Wiener F,Babonits M,Spira J,Bregula U,Klein G,Merwin RM,Asofsky R,Lynes M,Haughton G

    更新日期:1981-01-15 00:00:00

  • Clinical significance of CXCR3 and CXCR4 expression in primary melanoma.

    abstract::Tumor cell migration involved in metastases is a tightly regulated, nonrandom process. Chemokines have been identified as critical molecules guiding cell migration. We performed a prospective study to analyze a possible association between the expression of chemokine receptors CXCR3 and CXCR4 by primary melanoma and c...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21269

    authors: Longo-Imedio MI,Longo N,Treviño I,Lázaro P,Sánchez-Mateos P

    更新日期:2005-12-10 00:00:00

  • Mothers' active and passive smoking during pregnancy and risk of brain tumours in children.

    abstract::As part of a collaborative study of risk factors for childhood brain tumours, the effects of the mother's smoking and her potential for passive smoking exposure during the pregnancy were assessed in a case-control study. Parents of 91 cases and 321 population controls from Northern Italy, matched for age, sex and resi...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1002/ijc.2910570602

    authors: Filippini G,Farinotti M,Lovicu G,Maisonneuve P,Boyle P

    更新日期:1994-06-15 00:00:00

  • Clinicopathological and prognostic significance of circulating tumor cells in patients with gastric cancer: a meta-analysis.

    abstract::The prognostic significance of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in patients with gastric cancer (GC) is controversial. The aims of our meta-analysis are to assess its correlation with clinicopathological characteristics and prognostic significance in GC. PubMed, Embase, the Cochrane d...

    journal_title:International journal of cancer

    pub_type: 杂志文章,meta分析

    doi:10.1002/ijc.28954

    authors: Huang X,Gao P,Sun J,Chen X,Song Y,Zhao J,Xu H,Wang Z

    更新日期:2015-01-01 00:00:00

  • Oral contraceptive use, hormone replacement therapy, reproductive history and risk of colorectal cancer in women.

    abstract::Evidence from epidemiologic studies suggests a possible role of exogenous and endogenous hormones in colorectal carcinogenesis in women. However, with respect to exogenous hormones, in contrast to hormone replacement therapy, few cohort studies have examined oral contraceptive use in relation to colorectal cancer risk...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23079

    authors: Kabat GC,Miller AB,Rohan TE

    更新日期:2008-02-01 00:00:00

  • International patterns and trends in testis cancer incidence.

    abstract::Although the incidence of testis cancer has risen markedly in many Western populations over the past half-century, it is not clear whether rates in other populations also have increased. To clarify this issue, we examined testis cancer incidence rates over the 25-year time period of 1973-1997 for selected populations ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20931

    authors: Purdue MP,Devesa SS,Sigurdson AJ,McGlynn KA

    更新日期:2005-07-10 00:00:00

  • Racial/ethnic differences in colorectal cancer risk: the multiethnic cohort study.

    abstract::Incidence rates in the United States show clear racial/ethnic disparities for colorectal cancer. We examined the extent to which ethnic differences in risk factors could explain the age-adjusted variation in the risk of colorectal cancer, overall and by stage at diagnosis, among 165,711 African Americans, Japanese Ame...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25822

    authors: Ollberding NJ,Nomura AM,Wilkens LR,Henderson BE,Kolonel LN

    更新日期:2011-10-15 00:00:00

  • A pooled analysis of the outcome of prospective colonoscopic surveillance for familial colorectal cancer.

    abstract::Surveillance guidelines for the management of familial colorectal cancer (FCC), a dominant family history of colorectal cancer in which the polyposis syndromes and Lynch syndrome have been excluded, are not firmly established. The outcome of colonoscopic surveillance is studied using data from six centers. DNA mismatc...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1002/ijc.28397

    authors: Mesher D,Dove-Edwin I,Sasieni P,Vasen H,Bernstein I,Royer-Pokora B,Holinski-Feder E,Lalloo F,Evans DG,Forsberg A,Lindblom A,Thomas H

    更新日期:2014-02-15 00:00:00

  • Targeting multidrug resistant tumor cells with a recombinant single-chain FV fragment directed to P-glycoprotein.

    abstract::The MDR1 gene product P-glycoprotein (Pgp) plays a key role in multidrug resistance of cancer cells. Pgp is an ATP-driven efflux pump that extrudes a variety of dissimilar hydrophobic cytotoxic compounds. P-glycoprotein overexpression results in multidrug resistance (MDR) of tumor cell lines in vitro as well as in can...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.1552

    authors: Niv R,Assaraf YG,Segal D,Pirak E,Reiter Y

    更新日期:2001-12-15 00:00:00

  • Prevalence of the Rhesus-negative phenotype in Caucasian patients with small-cell lung cancer (SCLC).

    abstract::We report that the Rhesus (Rh)-negative phenotype is more prevalent in patients with small-cell lung cancer (SCLC) than in the normal Caucasian population (SCLC: 25% Rh-negative vs. 15% expected, p less than 0.0001). This finding has been validated for a Central and a Northern European population (Switzerland and UK)....

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910520328

    authors: Cerny T,Fey MF,Oppliger R,Castiglione M,Nachbur B,Gertsch M,Gasser A,Joss RA,Thatcher N,Lind M

    更新日期:1992-09-30 00:00:00

  • NK- and T-cell subsets in malignant mesothelioma patients: Baseline pattern and changes in the context of anti-CTLA-4 therapy.

    abstract::Malignant mesothelioma (MM) is a highly aggressive form of cancer with limited treatment options. Although the role of NK cells has been studied in many solid tumors, the pattern of NK-cell subsets and their recognition of mesothelioma cells remain to be explored. We used RNA expression data of MM biopsies derived fro...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32363

    authors: Sottile R,Tannazi M,Johansson MH,Cristiani CM,Calabró L,Ventura V,Cutaia O,Chiarucci C,Covre A,Garofalo C,Pontén V,Tallerico R,Frumento P,Micke P,Maio M,Kärre K,Carbone E

    更新日期:2019-10-15 00:00:00

  • Accuracy of human papillomavirus testing in primary screening of cervical neoplasia: results from a multicenter study in India.

    abstract::The knowledge that cervical neoplasia are caused by human papillomavirus (HPV) infection has led to the evaluation of its role in screening. We evaluated the accuracy of HPV testing by Hybrid capture II (HC II) method in detecting cervical intraepithelial neoplasia grade 2 and 3 (CIN 2 and 3) lesions in 4 cross-sectio...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1002/ijc.20396

    authors: Sankaranarayanan R,Chatterji R,Shastri SS,Wesley RS,Basu P,Mahe C,Muwonge R,Seigneurin D,Somanathan T,Roy C,Kelkar R,Chinoy R,Dinshaw K,Mandal R,Amin G,Goswami S,Pal S,Patil S,Dhakad N,Frappart L,Fontaniere B

    更新日期:2004-11-01 00:00:00

  • Residential and occupational exposure to 50-Hz magnetic fields and brain tumours in Norway: a population-based study.

    abstract::Our case-control study was conducted to investigate whether residential and occupational exposure to magnetic fields increased the risk for brain tumours in adults. Data from an occupational exposure matrix was also evaluated. The study population in this nested case-control study was made up of subjects aged 16 years...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20845

    authors: Klaeboe L,Blaasaas KG,Haldorsen T,Tynes T

    更新日期:2005-05-20 00:00:00

  • Expression of tissue inhibitor of matrix metalloproteinase-2 correlates with activation of matrix metalloproteinase-2 and predicts poor prognosis in tongue squamous cell carcinoma.

    abstract::Matrix metalloproteinase 2 (MMP-2) plays a crucial role in invasion and metastasis of malignant tumors. Membrane type 1-MMP (MT1-MMP) was originally identified as an activator of MMP-2. Tissue inhibitor of MMP-2 (TIMP-2) was identified as an inhibitor of MMP-2 and MT1-MMP. However, TIMP-2 was reported to be essential ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0215(20010120)95:1<44::aid-ijc1008>3.

    authors: Yoshizaki T,Maruyama Y,Sato H,Furukawa M

    更新日期:2001-01-20 00:00:00

  • Amplification of the MDM2 gene, but not expression of splice variants of MDM2 MRNA, is associated with prognosis in soft tissue sarcoma.

    abstract::The MDM2 gene encodes a 90-kDa oncoprotein that is overexpressed in several human carcinomas, osteosarcomas, gliomas and soft tissue sarcomas (STSs). This overexpression is the result of several mechanisms, for example, enhanced transcription or translation, gene amplification and alternative splicing. We found that 1...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0215(20010520)95:3<168::aid-ijc1029>3

    authors: Bartel F,Meye A,Würl P,Kappler M,Bache M,Lautenschläger C,Grünbaum U,Schmidt H,Taubert H

    更新日期:2001-05-20 00:00:00

  • A randomized, crossover, placebo- and moxifloxacin-controlled study to evaluate the effects of bosutinib (SKI-606), a dual Src/Abl tyrosine kinase inhibitor, on cardiac repolarization in healthy adult subjects.

    abstract::Effects of therapeutic and supratherapeutic concentrations of bosutinib, a dual Src/Abl tyrosine kinase inhibitor, on the corrected QT interval (QTc) in 60 healthy adults were assessed, according to ICH-E14 guidelines, in this 2-part, randomized, single-dose, double-blind, crossover, placebo- and open-label moxifloxac...

    journal_title:International journal of cancer

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1002/ijc.27348

    authors: Abbas R,Hug BA,Leister C,Sonnichsen D

    更新日期:2012-08-01 00:00:00

  • Prognostic relevance of MAGE-A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: a tissue microarray study.

    abstract::TAAs of the MAGE family are mostly studied as targets of specific immune responses. Their potential relevance as tumor markers has also been underlined. We used a MAb, 57B, recognizing MAGE-A4 protein in paraffin-embedded sections, to evaluate its expression in bladder cancers by employing TMA including 2,317 samples ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10540

    authors: Kocher T,Zheng M,Bolli M,Simon R,Forster T,Schultz-Thater E,Remmel E,Noppen C,Schmid U,Ackermann D,Mihatsch MJ,Gasser T,Heberer M,Sauter G,Spagnoli GC

    更新日期:2002-08-20 00:00:00

  • Secondary specific immune response in vitro to MSV tumor cells.

    abstract::The interactions which occur between antigenic tumor cells and normal or immune lymphoid cells in a 3-day in vitro culture, have been studied with a murine sarcoma virus (MSV)-induced tumor. The 3H-thymidine incorporation of lymphoma cells growing in suspension, and the radioactive-chromium release of freshly sampled ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910160609

    authors: Senik A,Hebrero FP,Levy JP

    更新日期:1975-12-15 00:00:00

  • Cancer incidence in a rural population of South Africa, 1998-2002.

    abstract::Cancer incidence rates and patterns are reported for a rural population, living in the Eastern Cape Province of South Africa for the period 1998-2002. The population-based cancer registry has operated for 20 years, using both active and passive methods for case finding, through collaborations with 19 health facilities...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25246

    authors: Somdyala NI,Bradshaw D,Gelderblom WC,Parkin DM

    更新日期:2010-11-15 00:00:00

  • The cannabinoid delta(9)-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells.

    abstract::Deregulation of cell survival pathways and resistance to apoptosis are widely accepted to be fundamental aspects of tumorigenesis. As in many tumours, the aberrant growth and survival of colorectal tumour cells is dependent upon a small number of highly activated signalling pathways, the inhibition of which elicits po...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22917

    authors: Greenhough A,Patsos HA,Williams AC,Paraskeva C

    更新日期:2007-11-15 00:00:00

  • Birth order and risk of childhood cancer: a pooled analysis from five US States.

    abstract::The causes of childhood cancers are largely unknown. Birth order has been used as a proxy for prenatal and postnatal exposures, such as frequency of infections and in utero hormone exposures. We investigated the association between birth order and childhood cancers in a pooled case-control dataset. The subjects were d...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1002/ijc.25593

    authors: Von Behren J,Spector LG,Mueller BA,Carozza SE,Chow EJ,Fox EE,Horel S,Johnson KJ,McLaughlin C,Puumala SE,Ross JA,Reynolds P

    更新日期:2011-06-01 00:00:00

  • Novel role for CRK adaptor proteins as essential components of SRC/FAK signaling for epithelial-mesenchymal transition and colorectal cancer aggressiveness.

    abstract::Epithelial-mesenchymal transition (EMT) is a cell plasticity process required for metastasis and chemoresistance of carcinoma cells. We report a crucial role of the signal adaptor proteins CRK and CRKL in promoting EMT and tumor aggressiveness, as well as resistance against chemotherapy in colorectal and pancreatic ca...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32955

    authors: Franke FC,Slusarenko BO,Engleitner T,Johannes W,Laschinger M,Rad R,Nitsche U,Janssen KP

    更新日期:2020-09-15 00:00:00

  • 7-Deoxynarciclasine shows promising antitumor efficacy by targeting Akt against hepatocellular carcinoma.

    abstract::Akt is a promising therapeutic target for cancer treatment. In our study, we have identified that 7-deoxynarciclasine (7-DONCS) is a potential inhibitor of Akt, which results in the repression of multiple oncogenic processes in hepatocellular carcinoma (HCC). We have found that 7-DONCS suppresses the growth of HCC by ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32395

    authors: Yin S,Qiu Y,Jin C,Wang R,Wu S,Liu H,Koo S,Han L,Zhang Y,Gao X,Pang X,Wang T,Yu H

    更新日期:2019-12-15 00:00:00

  • Intracellular localization of metaiodobenzyl guanidine in human neuroblastoma cells by electron spectroscopic imaging.

    abstract::The targeted radiotherapy of neuroblastoma with 131l-labelled metaiodobenzyl guanidine (mIBG) is now the subject of several clinical studies. The precise intracellular localization of mIBG, necessary for nuclear microdosimetry, has not previously been described. We report the use of electron-energy-loss spectroscopy a...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910470615

    authors: Gaze MN,Huxham IM,Mairs RJ,Barrett A

    更新日期:1991-04-01 00:00:00

  • Mitotic activity, apoptosis and TRPM-2 mRNA expression in DMBA-induced rat mammary carcinoma treated with anti-estrogen toremifene.

    abstract::Anti-estrogen toremifene inhibits growth of the 7,12-dimethylbenz(a)anthracene(DMBA)-induced rat mammary carcinoma. The changes in proliferation and cell death were studied in detail. Proliferation was measured by counting mitotic figures in histologic sections, expressed by volume-corrected mitotic index (M/V INDEX)....

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910550429

    authors: Huovinen R,Wärri A,Collan Y

    更新日期:1993-10-21 00:00:00