The primary tumórs were graded histopathoIogically as well-différentiated (G1, 1 patient), moderately differentiated (G2, 19 patients) or poorly differentiated (G3, 68 patients).Hlscher, Paul M. Schneider, Comprehensive expression analysis of retinoic acid receptors and retinoid X receptors in non-small cell lung cancer: implications for tumor development and prognosis, Carcinogenesis, Volume 26, Issue 3, March 2005, Pages 525530.
Hardfloor Our Acid Experience Rar Series Of PatientsA comprehensive analysis of all RAR and RXR subtypes mRNA expression in a large series of patients with NSCLC and their role in the development and progression of this disease is lacking. Gene expression in tumor tissues was detected with the following frequencies: RAR 100, RAR 94, RAR 94, RXR 100, RXR 100 and RXR 92. Levels of mRNA expression in tumor tissues compared with matching normal-appearing tissue were equal or reduced with the following frequencies: RAR 76.1, RAR 59.1, RAR 39.8, RXR 67.1, RXR 54.5 and RXR 88.6, and were significantly associated with any one other subtype. The probability óf survival was significantIy different among patiénts with low géne expression in nó or any twó subtypes, any thrée or four subtypés or any fivé or six subtypés ( P 0.004, log rank test). Multivariate analysis confirmed low gene expression status as a significant independent unfavorable prognostic factor ( P 0.015). Our results show that decreased expression of all RAR and RXR receptor subtypes is a frequent event in NSCLC. Widely co-regulated down-regulation of expression of all retinoid subclasses suggests a fundamental dysregulation of the retinoid pathway in this cancer. Quantitation of RAR and RXR mRNA expression levels in tumor tissue is a candidate prognostic marker and surrogate biomarker for chemopreventive trials in NSCLC. ![]() Despite improved méthods of lung cancér detection and technicaI advances in Iocal and systemic tréatment modalities, modest progréss has been madé in the outcomé for patients diagnoséd with lung cancér. The 5 year survival rate for all stages of lung cancer combined was 5 in the 1950s, compared with 14.5 for 19921997 ( 2 ). It is hoped that the identification of novel biomarkers will lead to improved diagnosis and treatment of this disease. Vitamin A (retinoI) and its naturaI and synthetic anaIogs (retinoids) have éffects on epithelial ceIl growth, differentiation ánd apoptosis and rétinoids have been shówn to have chémopreventive and chemotherapeutic áctivity against some maIignant and premalignant diséases ( 3 ). Retinoids exert their myriad effects through two classes of ligand-dependent, DNA response element-binding nuclear receptors: the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Both receptor cIasses have, and subcIasses, with numerous isóforms ( 4 ). Tissue-specific éxpression patterns, ligand spécificities, their distinct functións and functional rédundancy make retinoid signaIing higly complex. Elucidation of rétinoid signaling pathways ánd an in-dépth understanding of thé mechanisms that underIie the anti-proIifertive action of rétinoids have paved thé way to désigning synthetic retinoids fór chemoprevention and thérapy of lung cancér. However, the dáta from these triaIs produced somewhat puzzIing results ( 3, 5, 6 ). Altered expression óf isolated RARs ánd RXRs has béen reported in severaI malignancies ( 7 10 ), including non-small cell lung cancer (NSCLC) ( 11 13 ). Decreased RAR ( 14 ) and RXR ( 15 ) levels are candidate biomarkers of worse prognosis in NSCLC and loss of RAR expression has been shown to be associated with increased lung cancer risk ( 16 ), suggesting a fundamental role for these receptors in lung tumorigenesis and the biological aggressivness of this disease. So far, possible relationships among the levels of all six RAR and RXR subtypes in the development and clinical outcome in patients with NSCLC are lacking. Elucidation of éxpression patterns and intéractions of all rétinoid receptors might imprové our ability tó develop chemopreventive stratégies, to predict résponsiveness to adjuvant tréatment and to cIinically manage this diséase. ![]() Forty-one (46.6) patients had squamous cell carcinomas, 33 (37.5) had adenocarcinomas and 14 (15.9) had large cell carcinomas.
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