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  • Title: Chemotherapeutic evaluation of 4-hydroxybenzylretinone (4-HBR), a nonhydrolyzable C-linked analog of N-(4-hydroxyphenyl) retinamide (4-HPR) against mammary carcinogenesis.
    Author: Abou-Issa H, Curley RW, Alshafie GA, Weiss KL, Clagett-Dame M, Chapman JS, Mershon SM.
    Journal: Anticancer Res; 2001; 21(6A):3839-44. PubMed ID: 11911255.
    Abstract:
    The antitumor effects of N-(4-hydroxyphenyl)retinamide (4-HPR), and its stable C-linked analog, 4-hydroxybenzylretinone (4-HBR) on the regression of established 7,12-dimethylbenz(a)anthracene(DMBA)-induced rat mammary tumors were compared. 4-HBR is a stable and nonhydroyzable derivative which cannot be converted in vivo to retinoic acid (RA). The results indicate that 4-HBR decreased mammary tumor volumes to the same extent as equimolar concentration (2 mmol/kg diet) of 4-HPR (-45% for 4-HBR vs. -42% for 4-HPR, p<0.01). Both 4-HPR and 4-HBR bind very poorly to nuclear retinoid receptors RARs and RXRs. The similarity of physicochemical properties of 4-HPR and 4-HBR as well as their equal antitumor potency suggests that 4-HPR like 4-HBR, is acting directly rather than through hydrolysis to free RA. Treatment with 4-HPR caused an almost 65% decrease in serum retinol levels. These results suggest that 4-HBR may have a significant chemotherapeutic advantage over 4-HPR, as the nonhydrolyzable analog may not cause night blindness which occurs as a significant side effect of 4-HPR usage.
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