Titre du document / Document title

Time course of fenretinide-induced modulation of circulating insulin-like growth factor (IGF)-I, IGF-II and IGFBP-3 in a bladder cancer chemoprevention trial

Auteur(s) / Author(s)

TORRISI R. ⁽¹⁾ ; MEZZETTI M. ⁽²⁾ ; JOHANSSON H. ^{(3 4)} ; BARRECA A. ⁽⁴⁾ ; PIGATTO F. ⁽¹⁾ ; ROBERTSON C. ⁽²⁾ ; DECENSI A. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Chemoprevention Unit, European Institute of Oncology, Milan, ITALIE
⁽²⁾ Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, ITALIE
⁽³⁾ Service of Laboratory Medicine, European Institute of Oncology, Milan, ITALIE
⁽⁴⁾ Department of Endocrinology and Metabolic Sciences, University of Genova, Genoa, ITALIE

Résumé / Abstract

The insulin-like growth factor (IGF) system is widely involved in human carcinogenesis. A significant association between high circulating IGF-I concentrations and an increased risk of lung, colon, prostate and pre-menopausal breast cancer has recently been reported. Lowering plasma IGF-I may thus represent an attractive strategy to be pursued for chemopreventive purposes. We have previously shown that the synthetic retinoid fenretinide (4-HPR) lowers plasma IGF-I in pre-menopausal breast cancer patients. We investigated the effect of fenretinide on circulating IGF-I, IGF-II and IGFBP-3 measured at yearly intervals during the 2-year treatment period and one year after treatment discontinuation in a predominantly male population of patients with superficial bladder cancer. Repeated measures analysis, after adjustment for age, body mass index (BMI) and year of study, showed a significant effect of fenretinide on IGF-I levels, which were further lowered after the second year of treatment and only partially recovered after drug discontinuation. Differently from breast cancer patients, the effect of fenretinide was not modified by age. No significant effect was evident on IGFBP-3, IGF-II and the IGF-I+IGF-II/IGFBP-3 molar ratio, expressing the tissue availability of the mitogenic peptides, although IGF-II and the molar ratio were lowered by treatment by an overall mean of 16% and 15%, respectively. Given the increasingly recognized importance of circulating IGFs in the pathogenesis of different solid tumors, our findings strengthen the rationale for studying fenretinide as a chemopreventive agent.

Revue / Journal Title

International journal of cancer   ISSN 0020-7136   CODEN IJCNAW 

Source / Source

2000, vol. 87, n^o4, pp. 601-605 (30 ref.)

Langue / Language

Anglais

Editeur / Publisher

Wiley-Liss, New York, NY, ETATS-UNIS  (1966) (Revue)

Mots-clés anglais / English Keywords

Malignant tumor ; Urinary bladder ; Fenretinide ; Antineoplastic agent ; Retinoic acid ; Chemotherapy ; Treatment ; Time ; Insulin like growth factor 1 ; Insulin like growth factor 2 ; Insulin like growth factor binding protein ; Chemoprophylaxis ; Prevention ; Clinical trial ; Male ; Age ; Human ; Retinoid ; Urinary system disease ; Urinary tract disease ; Bladder disease ; Growth factor ; Polypeptide ;

Mots-clés français / French Keywords

Tumeur maligne ; Vessie urinaire ; Fenrétinide ; Anticancéreux ; Rétinoïque acide ; Chimiothérapie ; Traitement ; Temps ; Facteur croissance IGF1 ; Facteur croissance IGF2 ; Protéine liaison IGFBP ; Chimioprophylaxie ; Prévention ; Essai clinique ; Mâle ; Age ; Homme ; Rétinoïde ; Appareil urinaire pathologie ; Voie urinaire pathologie ; Vessie pathologie ; Facteur croissance ; Polypeptide ;

Mots-clés espagnols / Spanish Keywords

Tumor maligno ; Vejiga ; Fenretinida ; Anticanceroso ; Retinoico ácido ; Quimioterapia ; Tratamiento ; Tiempo ; Factor crecimiento IGF1 ; Factor crecimiento IGF2 ; Proteína enlace IGFBP ; Quimioprofilaxis ; Prevención ; Ensayo clínico ; Macho ; Edad ; Hombre ; Retinoide ; Aparato urinario patología ; Vía urinaria patología ; Vejiga patología ; Factor crecimiento ; Polipéptido ;

Localisation / Location

INIST-CNRS, Cote INIST : 13027, 35400009098857.0220