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.
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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DOI：
10.1007/s10549-011-1724-7
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发表时间：
2012-05
影响因子：
3.8
通讯作者：
Njar, Vincent C. O.
中科院分区：
文献类型：
--
作者：
Goss, Paul E.;Qi, Shangle;Hu, Haiqing;Gediya, Lalji K.;Purushottamachar, Puranik;Godbole, Abhijit M.;Njar, Vincent C. O.
关键词：
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.
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影响因子：
4.3
作者：
Thatcher JE;Isoherranen N
通讯作者：
Isoherranen N
影响因子：
2.7
作者：
Njar, VCO;Nnane, IP;Brodie, AMH
通讯作者：
Brodie, AMH
DOI：
10.1634/theoncologist.5-5-361
发表时间：
2000-01-01
期刊：
The oncologist
影响因子：
--
作者：
Dragnev, K H;Rigas, J R;Dmitrovsky, E
通讯作者：
Dmitrovsky, E
DOI：
10.1016/j.jchromb.2004.07.028
发表时间：
2004-10-25
影响因子：
3
作者：
Wu, CY;Njar, V;Nnane, I
通讯作者：
Nnane, I
影响因子：
11.2
作者：
Belosay, Aashvini;Brodie, Angela M. H.;Njar, Vincent C. O.
通讯作者：
Njar, Vincent C. O.