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Titolo:
Nuclear expression of human apurinic/apyrimidinic endonuclease (HAP1/REF-1) in head-and-neck cancer is associated with resistance to chemoradiotherapy and poor outcome
Autore:
Koukourakis, MI; Giatromanolaki, A; Kakolyris, S; Sivridis, E; Georgoulias, V; Funtzilas, G; Hickson, ID; Gatter, KC; Harris, AL;
Indirizzi:
Univ Hosp, Dept Radiotherapy & Oncol, Iraklion 71306, Crete, Greece Univ Hosp Iraklion Crete Greece 71306 ncol, Iraklion 71306, Crete, Greece Democritus Univ Thrace, Dept Pathol, Alexandroupolis, Greece Democritus Univ Thrace Alexandroupolis Greece , Alexandroupolis, Greece Aristotelian Univ Salonika, AHEPA Hosp, Dept Med Oncol, Hellen Cooperat Oncol Grp, GR-54006 Salonika, Greece Aristotelian Univ Salonika Salonika Greece GR-54006 006 Salonika, Greece Osford Radcliffe Hosp, Dept Cellular Sci, Oxford, England Osford RadcliffeHosp Oxford England Dept Cellular Sci, Oxford, England Osford Radcliffe Hosp, Imperial Canc Res Fund, Mol Oncol Lab, Oxford, England Osford Radcliffe Hosp Oxford England nd, Mol Oncol Lab, Oxford, England
Titolo Testata:
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
fascicolo: 1, volume: 50, anno: 2001,
pagine: 27 - 36
SICI:
0360-3016(20010501)50:1<27:NEOHAE>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
SQUAMOUS-CELL CARCINOMA; REPAIR ENZYME HAP1; DNA-REPAIR; PROTEIN; RADIATION; REF-1; P53; LINES; IDENTIFICATION; OVEREXPRESSION;
Keywords:
HAP1; p53; radiotherapy; chemotherapy; head-and-neck cancer;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Koukourakis, MI Tumour & Angiogenesis Res Grp, 18 Dimokratias Ave, Iraklion 71306, Crete, Greece Tumour & Angiogenesis Res Grp 18 Dimokratias Ave Iraklion Crete Greece 71306
Citazione:
M.I. Koukourakis et al., "Nuclear expression of human apurinic/apyrimidinic endonuclease (HAP1/REF-1) in head-and-neck cancer is associated with resistance to chemoradiotherapy and poor outcome", INT J RAD O, 50(1), 2001, pp. 27-36

Abstract

Purpose: HAP1/Ref-1 endonuclease is involved in the repair of DNA strand breaks and in the activation of DNA binding of several transcription factors. HAP1 is also a potent activator of wild type p53, It therefore has multiple possible roles in the response of human cancer to radiotherapy and chemotherapy. Methods and Materials: The nuclear expression of HAP1 and p53 proteins wasstudied by immunohistochemistry in paraffin-embedded material from 95 patients with locally advanced squamous cell head-and-neck cancer (HNC) treatedwith radical radiotherapy (38 cases with induction platinum-based chemotherapy and 57 with concurrent platinum chemoradiotherapy),Results: HAP1 was present in the nuclei of normal epithelium and stromal cells. Loss of HAP1 nuclear expression was frequently noted in cancer cells. Tumors with high HAP1 nuclear expression (% of positive cells > mean; mean= 11%) were of good differentiation (p = 0.06) and presented frequently with advanced nodal disease (p 0.01). High nuclear HAP1 expression was significantly associated with poor complete response rate (p = 0.00001), shorter local relapse-free interval (p < 0.0001), and poorer survival (p < 0.0008),HAP1 nuclear reactivity was inversely associated with p53 nuclear accumulation (p = 0.003). The inverse correlation between HAP1 expression and prognosis was independent of p53 status. Conclusion: HAP1 nuclear expression in HNC is inversely associated with p53 nuclear accumulation and directly related to resistance to chemoradiotherapy and poor survival. Further clinical investigation is required to confirm these findings. (C) 2001 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/07/20 alle ore 01:26:47