ISSN:
0730-2312
Keywords:
bladder cancer
;
chemoprevention
;
F-actin
;
G-actin
;
intermediate biomarker
;
intermediate endpoint biomarker
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
The understanding of intermediate endpoint biomarker expression in relation to the sequential events in bladder tumorigensesis establishes a useful approach for evaluating chemopreventive agents. Biomarkers may be genotypic or phenotypic and function as biomarkers of susceptibility, expouser, effect, or disease. This paper reviews serverla years or reserach on biomarkers and their use in monitoring chemoprevention therapy. In initial animal experimnets, mice were doesed with N-butyl-N-(4-hydroxybutyl) nitrosamine(OH-BBN) while co-administering N(4-hydroxyphenyl) retinamide (4-HPR). 4-HPR did not statistically reduce tumor incidence, but did affect tumor dfferentiation and consequently, nuclear size and DNA ploidy. These results suggest that nuclear size and ploidy may function as intermediate endpoint biomarkers of effect for oncogenesis and that epigenetic as well as genetic mechanisms may be primary in the oncogenic proces. Early biomarkers of effect which occur prior to genetic effects or chromosome aberration may portend a higher probability of being modulated by differentiating agents such as retinoids. In vitro studies demonstrated that RPMI-7666 cells cultured with a phorbol ester tumor promoter (12O-tetradecanoyl-phorbol-13-acetate) could be redifferentiatee with 13-cis-retinoic acid and dimethyl sulfoxide (DMSO). F-Actin, A cytoskeltal biomerker with a presumed function in the epigenetic mechanisms of carcinogenesis, could also be normalized in HL-60 cells treated with 4-HPR or DMSO.A clinical evaluation of F-actin in patients whith varying degrees of risk confirmed the value of F-actin as a differentiating biomarker useful for bladder cancer risk assessment. The clarification of when the photypic changes of F-acting occur in biomerker useful for bladder cancer risk assessment. The clarification of when the phenotypic changes of F-actin occur in the oncogenic process was achieved when a variety of biochemical changes were mapped in the patients with bladder cancer. There stuides confirmed that G-acting, a reciprocal form of F-actin, is increased relatively early in bladder cancer oncogenesis when multiple biomarkers are quantiated in the field, adjacent area, and the tumor. Comparison of each individual biomarker's expression from field, adjacent to tumor, and tumor, and subsequent cluster analysis of these biomarkers, indicated that the possible sequences of phenotypic expression of biomarkers in bladder cancer oncogenesis is from G-actin, to p300 antigen, to epidermal growth factor receptor (EGFR), to p185, (neu oncogene product), to DNA aneuploidy and family, finally, to visual morphology. To date, a bettery of three biomarkers, G-actin, M344, and DNA, with routine cytology has been used to monitor eleven patients receiving Bacillus Calmette-Guerin(BCG) immunotherapy and eight patients clinically free of bladder cancer (negative cytology and biopsy) who were treated with differentiation agent, DMSO. These results indicate that G-actin may be useful biomarker for evaluating the efficacy of chemopreventive agents. © 1992 Wiley-Liss, Inc.
Additional Material:
7 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcb.240501320
Permalink
