1,1,2-Triphenylbut-1-enes, which are substituted with acetoxy groups on one, two, or three aromatic rings in the para and/or meta positions, were synthesized. The identity of the occurring E and Z isomers were established by 1H NMR spectroscopy. A study on structure-activity relationships was carried out with regard to estradiol receptor affinity and to inhibiting effects on the growth of a postmenopausal human mammary carcinoma implanted in nude mice. The para-substituted compounds generally exhibited a higher receptor affinity and a better antitumor activity than the corresponding meta-substituted ones. The E isomers were superior to the respective Z isomers in those two properties. The tumor-inhibiting effect of the mono- and disubstituted compounds was better than that of the trisubstituted ones. Except for the trisubstituted compounds, they all show a good correlation between estradiol receptor affinity and antitumor activity. One of the compounds was also tested on the 9,10-dimethylbenz[a]-anthracene-induced, hormone-dependent mammary carcinoma of the Sprague-Dawley rat, and the results corresponded to those obtained in the xenograft tumor.

37 (85%) of 44 human breast cancers are successfully transplanted on thymus-aplastic nu/nu-mice without adjunctive immunotherapy. 16 weeks after transplantation 4 rapidly growing tumours are showing human, female karyotypes. Subsequent investigations proved a good correlation between original tumour and transplant: histology, 3H-thymidine marking index and receptors of androgen and estorgen.

Refractory chronic GVHD (cGVHD) remains a major cause of morbidity after transplantation. Many drugs are used but there is no consensus on the standard of care. We investigated the efficacy of TLI in corticosteroid-refractory cGVHD. We analyzed retrospectively 31 patients receiving one or more TLI session for refractory cGVHD from 2000 to 2007. The main objective was to evaluate the response rate after TLI. Decreased corticosteroid doses and/or discontinued immunosuppressive agents were considered to be surrogate markers of response. All but one patient presented with severe cGVHD at the time of TLI. The median number of previous immunosuppressive treatment lines was 3 (range: 2-4). Fourteen patients (45%) achieved an objective response after TLI and 8 (25%) were cGVHD free at long-term follow-up. In all, 5 (29%) of the 17 nonresponsive patients did not show the features of progressive cGVHD and could decrease the amount of immunosuppressive drugs taken. Response after TLI significantly improved 5-year GVHD-related mortality (14% vs 42%, P ¼ 0.038) but not OS (58%vs 64% P ¼ 0.27). Regarding the promising response rate in this heavily pretreated population, we reasoned that TLI could be an alternative treatment for corticosteroid-refractory cGVHD.

3,3'-Diacetoxy-alpha, beta-dialkylstilbenes (alkyl = CH3 to C4H9, 1-4) 3,3'-dihydroxy-alpha, beta-diethylstilbene (5), and their corresponding stilbene oxides (6-10) were synthesized. Compounds 1-10 competitively antagonized in vitro the interaction of [3H]estradiol with its receptor. 3,3'-Diacetoxy-alpha, beta-diethylstilbene (2), 3,3'-diacetoxy-alpha, beta-diethylstilbene oxide (7), and their phenolic analogues (5 and 10) were most effective. Shortening or lengthening the alkyl side chains led to a decrease in receptor affinity. Among the stilbenes and epoxides, those with C2H5 and C3H7 groups (2, 3, 5 and 7, 8, 10) caused the strongest inhibition of the growth of a hormone-dependent postmenopausal human mammary carcinoma serially implanted in nude mice. The strong antitumor activity of 5 and 10 was confirmed by experiments on the 9,10-dimethyl-1,2-benzanthracene-induced, hormone-dependent mammary carcinoma of the Sprague-Dawley rat.