Activity of 4-HPR in superficial bladder cancer using DNA flow cytometry as an intermediate endpoint

A. Decensi, S. Bruno, W. Giaretti, R. Torrisi, A. Curotto, B. Gatteschi, E. Geido, A. Polizzi, M. Costantini, P. Bruzzi, G. Nicolo, A. Costa, F. Boccardo, L. Giuliani, L. Santi

Research output: Contribution to journalArticlepeer-review

Abstract

The ability of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) to affect the outcome of previously resected superficial bladder cancer was investigated in a pilot study using DNA content flow cytometry and conventional cytology as intermediate endpoints. Twelve patients were treated with oral 4-HPR (200 mg daily) and compared with 17 non-randomized, untreated controls. The median interval between transurethral resection and 4-HPR administration was 5.5 months (range 0-36). The median follow-up period was 12 months (range 3-31) in the 4-HPR group and 9 months (range 2-22) in the control group. The proportion of patients with DNA aneuploid stemlines in bladder-washed cells decreased from 7/12 (58%) to 5/11 (45%) in the 4-HPR group, but increased from 7/17 (41%) to 10/17 (59%) in the control group. In patients with stable diploid profiles, mean (±SE) S-phase and G2 + M-phase fractions decreased in the course of retinoid treatment from basal levels of 15.2 ± 4.1% to 7.5 ± 3.3% and 10.3 ± 2.2% to 5.2 ± 0.4%, respectively. The same parameters in the control group changed from basal levels of 14.6 ± 3.4% to 12.4 ± 2.7% and 9.8 ± 1.6% to 12.6 ± 1.6%, respectively. Positive or suspicious cytologic examinations were present in 3/12 (25%) treated cases prior to 4-HPR administration and all subsequently reverted to normal. The same parameter in the control group increased from 4/17 (24%) to 6/17 (35%) during follow-up. Impaired adaptation to darkness was recorded in 4 patients, and transient dermatologic alterations were observed in one-third of the patients, requiring dose reduction in one case. Our preliminary data suggest that 4-HPR may affect the DNA content and abnormal cytology in patients with previously resected superficial bladder cancer.

Original languageEnglish
Pages (from-to)139-147
Number of pages9
JournalJournal of Cellular Biochemistry
Volume50
Issue numberSUPPL. 16 I
Publication statusPublished - 1992

Keywords

  • 4-HPR
  • bladder cancer
  • chemoprevention
  • DNA flow cytometry
  • intermediate endpoints
  • retinoids

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Medicine(all)

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