Purushottamachar Puranik - Anti-tumor effects of a novel retinoic acid metabolism blocking agent VN/14-1 in the N-methyl-N-nitrosourea-induced rat mammary carcinoma model and its effects on the uterus.

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  Publication Details (including relevant citation   information):

  Breast Cancer Res   Treat. 2011 Aug 14. [Epub ahead of print]

  Abstract:

  VN/14-1 [4-(±)-(1H-Imidazol-1-yl)-(E)-retinoic acid], a novel   retinoic acid metabolism blocking agent (RAMBA), works by   inhibiting the breakdown of all-trans-retinoic acid. The purpose   of this study was to evaluate the anti-tumor effects of VN/14-1   on the N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinoma   model, and peripheral organ effects on the uteri of immature   ovariectomized (OVX) rats. In tumor burden experiments, after 56   days of administration of VN/14-1 5, 10, and 20 mg/kg/day,   significant tumor reductions in mean tumor weight of 19.1, 34.4,   and 44.3%, compared to tumors in control animals occurred.   Cumulative tumor growth was also significantly slower in a   dose-dependent manner in groups receiving 5, 10, and 20 mg/kg/day   of VN/14-1 compared to growth rates in the control group. Tumor   apoptosis was significant increases in animals treated with 5,   10, and 20 mg/kg/day of VN/14-1. In uterotrophic experiments,   immature OVX rats given VN/14-1 significantly reduced uterine   weight and blocked endometrial stimulation induced by unopposed   β-estradiol (E2). In both rat models, adverse toxicities included   weakness, anorexia, and reduction in body weight in the groups   given the highest dose of 20 mg/kg/day. In summary, VN/14-1   inhibited tumor growth in the MNU-induced estrogen receptor   (ER)-positive rat mammary tumor model, and antagonized the   stimulatory effect of estrogens on the uterus. The studies   suggest that VN/14-1 may be a useful novel therapy for   ER-positive breast cancer.

 

 
   
      PMID: 21842418    
 

  Address (URL): http://www.ncbi.nlm.nih.gov/pubmed/21842418

 

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