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  1. Article ; Online: Using the genomic adjusted radiation dose (GARD) to personalize the radiation dose in nasopharyngeal cancer.

    Leung Chiang, Chi / Sik Kwan Chan, Kenneth / Li, Huaping / Tong Ng, Wai / Chung Hang Chow, James / Cheuk Wai Choi, Horace / On Lam, Ka / Ho Fun Lee, Victor / Kai Cheong Ngan, Roger / Wing Mui Lee, Anne / Eschrich, Steven A / Torres-Roca, Javier F / Wing Hon Wong, Jason

    Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology

    2024  , Page(s) 110287

    Abstract: Background: Locally advanced nasopharyngeal cancer (NPC) patients undergoing radiotherapy are at risk of treatment failure, particularly locoregional recurrence. To optimize the individual radiation dose, we hypothesize that the genomic adjusted ... ...

    Abstract Background: Locally advanced nasopharyngeal cancer (NPC) patients undergoing radiotherapy are at risk of treatment failure, particularly locoregional recurrence. To optimize the individual radiation dose, we hypothesize that the genomic adjusted radiation dose (GARD) can be used to correlate with locoregional control.
    Methods: A total of 92 patients with American Joint Committee on Cancer / International Union Against Cancer stage III to stage IVB recruited in a randomized phase III trial were assessed (NPC-0501) (NCT00379262). Patients were treated with concurrent chemo-radiotherapy plus (neo) adjuvant chemotherapy. The primary endpoint is locoregional failure free rate (LRFFR).
    Results: Despite the homogenous physical radiation dose prescribed (Median: 70 Gy, range 66-76 Gy), there was a wide range of GARD values (median: 50.7, range 31.1-67.8) in this cohort. In multivariable analysis, a GARD threshold (GARD
    Conclusion: GARD is independently associated with locoregional control in radiotherapy-treated NPC patients from a Phase 3 clinical trial. GARD may be a potential framework to personalize radiotherapy dose for NPC patients.
    Language English
    Publishing date 2024-04-16
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 605646-5
    ISSN 1879-0887 ; 0167-8140
    ISSN (online) 1879-0887
    ISSN 0167-8140
    DOI 10.1016/j.radonc.2024.110287
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1926: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Multigene pathway-based analyses identify nasopharyngeal carcinoma risk associations for cumulative adverse effects of TERT-CLPTM1L and DNA double-strand breaks repair.

    Yee Ko, Josephine Mun / Dai, Wei / Wun Wong, Elibe Hiu / Kwong, Dora / Tong Ng, Wai / Lee, Anne / Kai Cheong Ngan, Roger / Chung Yau, Chun / Tung, Stewart / Li Lung, Maria

    International journal of cancer

    2014  Volume 135, Issue 7, Page(s) 1634–1645

    Abstract: The genetic etiology of nasopharyngeal carcinoma (NPC) and mechanisms for inherited susceptibility remain unclear. To examine genetic risk factors for NPC, we hypothesized that heritable risk is attributable to cumulative effects of multiple common low- ... ...

    Abstract The genetic etiology of nasopharyngeal carcinoma (NPC) and mechanisms for inherited susceptibility remain unclear. To examine genetic risk factors for NPC, we hypothesized that heritable risk is attributable to cumulative effects of multiple common low-risk variants. With the premise that individual SNPs only confer subtle effects for cancer risk, a multigenic pathway-based approach was used to systematically examine associations between NPC genetic susceptibility with SNPs in genes in DNA repair pathways and from previously identified cancer genome-wide association study analyses. This case-control study covers 161 genes/loci and focuses on pathway-based analyses in 2,349 Hong Kong individuals, allowing stratification according to NPC familial status for meaningful association analysis. Three SNPs (rs401681, rs6774494 and rs3757318) corresponding to TERT/CLPTM1L (OR 95% CI = 0.77, 0.68-0.88), MDS1-EVI1 (OR 95% CI=0.79 0.69-0.89) and CCDC170 (OR 95% CI = 0.76, 0.66-0.86) conferred modest protective effects individually for NPC risk by the logistic regression analysis after multiple testing adjustment (p(Bonferroni)  < 0.05). Stratification of NPC according to familial status identified rs2380165 in BLM (OR 95% CI = 1.49, 1.20-1.86, p(Bonferroni)  < 0.05) association with family history-positive NPC (FH+ NPC) patients. Multiple SNPs pathway-based analysis revealed that the combined gene dosage effects for increasing numbers of unfavorable genotypes in TERT-CLPTM1L and double-strand break repair (DSBR) conferred elevated risk in FH+ and sporadic NPC patients (ORs per allele, 95% CIs = 1.37, 1.22-1.55, p(Bonferroni)  = 5.00 × 10(-6); 1.17, 1.09-1.26, p(Bonferroni)  = 4.58 × 10(-4) , respectively, in TERT/NHEJ pathways). Our data suggested cumulative increased NPC risk associations with TERT-CLPTM1L and DSBR pathways contribute to genetic susceptibility to NPC and have potential translational relevance for patient stratification and therapeutics.
    MeSH term(s) Biomarkers, Tumor/genetics ; Carcinoma ; Case-Control Studies ; DNA Breaks, Double-Stranded ; DNA Repair/genetics ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Genotype ; Humans ; Male ; Membrane Proteins/genetics ; Middle Aged ; Multigene Family ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/genetics ; Neoplasm Proteins/genetics ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/genetics ; Prognosis ; Risk Factors ; Signal Transduction ; Telomerase/genetics
    Chemical Substances Biomarkers, Tumor ; CLPTM1L protein, human ; Membrane Proteins ; Neoplasm Proteins ; TERT protein, human (EC 2.7.7.49) ; Telomerase (EC 2.7.7.49)
    Language English
    Publishing date 2014-03-04
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218257-9
    ISSN 1097-0215 ; 0020-7136
    ISSN (online) 1097-0215
    ISSN 0020-7136
    DOI 10.1002/ijc.28802
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 478: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 576: Show issues

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