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Antitumor effects of combination toremifene and medroxyprogesterone acetate (MPA) in vitro and in vivo 托瑞米芬与醋酸甲孕酮(MPA)联合用药的体内外抗肿瘤作用
Journal of steroid biochemistry Pub Date : 1990-06-22 DOI: 10.1016/0022-4731(90)90020-S
L. Kancas , M. Grönroos
{"title":"Antitumor effects of combination toremifene and medroxyprogesterone acetate (MPA) in vitro and in vivo","authors":"L. Kancas ,&nbsp;M. Grönroos","doi":"10.1016/0022-4731(90)90020-S","DOIUrl":"10.1016/0022-4731(90)90020-S","url":null,"abstract":"<div><p>The estrogen (ER) and progesterone (PgR) receptor levels in various gynecological tumors were measured. The same tumors were exposed <em>in vitro</em> to toremifene, MPA or their combination and the growth of the tumors was followed by measuring the adenosine triphosphate (ATP) within the cells by a simple bioluminescence assay. Altogether 34 clinical samples were studied. DMBA-induced mammary tumors bearing rats were treated <em>in vivo</em> with toremifene, MPA and their combination.</p><p>About half of the ovarian cancers and 6 out of the 7 adenocarcinomas of uteri contained ER. The ovarian tumors were PgR rich in 25% and adenocarcinomas of uteri in 6 out of the 7 cases.</p><p>When compared to control toremifene (concentration 1 μmol/l) was able to decrease the number of living cells to 50% or less in 9/34 samples, MPA (concentration 10 μmol/l) in 17/34 samples, and the combination in 25/34 samples. In five cases the antitumor effect of the combination was synergistic. In two cases signs of weak antagonism were seen.</p><p><em>In vivo</em> the antitumor effect of toremifene and MPA was clearly synergistic against DMBA-induced cancers. The effect was dose-dependent and at sufficiently high doses it was possible to eradicate the tumors and cure the animals.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 3","pages":"Pages 253-257"},"PeriodicalIF":0.0,"publicationDate":"1990-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90020-S","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13296359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Antiestrogenic and antitumor properties of the new triphenylethylene derivative toremifene in the rat 新型三苯基乙烯衍生物托瑞米芬在大鼠体内的抗雌激素和抗肿瘤特性
Journal of steroid biochemistry Pub Date : 1990-06-22 DOI: 10.1016/0022-4731(90)90005-D
E. Di Salle, T. Zaccheo, G. Ornati
{"title":"Antiestrogenic and antitumor properties of the new triphenylethylene derivative toremifene in the rat","authors":"E. Di Salle,&nbsp;T. Zaccheo,&nbsp;G. Ornati","doi":"10.1016/0022-4731(90)90005-D","DOIUrl":"10.1016/0022-4731(90)90005-D","url":null,"abstract":"<div><p>The effects of toremifene, a new triphenylethylene derivative, on the uterus and DMBA-induced mammary tumors in rats were compared to tamoxifen. The ability of toremifene to compete with [<sup>3</sup>H]estradiol for cytoplasmic estrogen receptor from rat uterus was similar to tamoxifen, the IC<sub>50</sub>, being 26 and 23 μM respectively.</p><p>In immature intact rats the two compounds, administered orally for three consecutive days, had similar intrinsic partial estrogenic efficacy, at 50 mg/kg, about 40% of that of estradiol benzoate (EB). However, at doses ⩽ 10 mg/kg, the estrogenic effect of toremifene was seen at doses about 40 times higher than that of tamoxifen. The two compounds, administered together with a standard dose of EB, expressed the same maximal antiestrogenic efficacy (about 65% inhibition) at 50 mg/kg. However, the minimal effective antiestrogenic dose of toremifene was about 10 times that of tamoxifen and the ratio between antiestrogenic/estrogenic properties was favourable to toremifene.</p><p>The duration of the antiestrogenic (antiuterotrophic) effect of a single oral dose (10 mg/kg) of the two compounds proved similar: at least 4 days in intact rats and 3 days in ovariectomized rats.</p><p>In DMBA-induced tumor bearing rats toremifene was administered p.o., 6 times/week for 4 weeks at 0.08, 0.4, 2, 10 and 50 mg/kg. It was effective at the doses of 2, 10 and 50 mg/kg, inducing 39, 35 and 46% tumor regressions. The activity of toremifene at the minimal effective dose of 2 mg/kg was then compared with that of tamoxifen given at the same dose level. The compounds had comparable activity (47 vs 44% tumor regressions).</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 3","pages":"Pages 203-206"},"PeriodicalIF":0.0,"publicationDate":"1990-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90005-D","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13296444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 70
Response to toremifene (Fc-1157a) therapy in tamoxifen failed patients with breast cancer. Preliminary communication 他莫昔芬治疗失败的乳腺癌患者对托瑞米芬(Fc-1157a)治疗的反应。初步的沟通
Journal of steroid biochemistry Pub Date : 1990-06-22 DOI: 10.1016/0022-4731(90)90016-L
S.R. Ebbs, J. Roberts, M. Baum
{"title":"Response to toremifene (Fc-1157a) therapy in tamoxifen failed patients with breast cancer. Preliminary communication","authors":"S.R. Ebbs,&nbsp;J. Roberts,&nbsp;M. Baum","doi":"10.1016/0022-4731(90)90016-L","DOIUrl":"10.1016/0022-4731(90)90016-L","url":null,"abstract":"<div><p>Nine patients with measurable lesions of locally advanced or recurrent breast cancer have been treated with toremifene 200 mg daily. A response rate of 33% [complete remission (CR) + partial remission (PR)] or 78% [CR + PR + no change (NC)] has been achieved so far. As all our patients had previously relapsed on anti-oestrogen therapy (tamoxifen), we postulate that our response rate was achieved by a direct oncolytic effect.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 3","pages":"Page 239"},"PeriodicalIF":0.0,"publicationDate":"1990-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90016-L","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13296355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 21
Forthcoming papers in the journal of steroid biochemistry 类固醇生物化学杂志即将发表的论文
Journal of steroid biochemistry Pub Date : 1990-06-22 DOI: 10.1016/0022-4731(90)90022-K
{"title":"Forthcoming papers in the journal of steroid biochemistry","authors":"","doi":"10.1016/0022-4731(90)90022-K","DOIUrl":"https://doi.org/10.1016/0022-4731(90)90022-K","url":null,"abstract":"","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 3","pages":"Page I"},"PeriodicalIF":0.0,"publicationDate":"1990-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90022-K","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137201900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Toremifene, a new antiestrogenic compound in the treatment of metastatic mammary cancer. A phase II study 托瑞米芬，一种治疗转移性乳腺癌的新型抗雌激素化合物。II期研究
Journal of steroid biochemistry Pub Date : 1990-06-22 DOI: 10.1016/0022-4731(90)90013-I
Stein Gundersen
{"title":"Toremifene, a new antiestrogenic compound in the treatment of metastatic mammary cancer. A phase II study","authors":"Stein Gundersen","doi":"10.1016/0022-4731(90)90013-I","DOIUrl":"10.1016/0022-4731(90)90013-I","url":null,"abstract":"<div><p>Toremifene is a new antiestrogenic compound. Toremifene has definite antitumor effect in advanced breast cancer. The response rate in the present phase II study among postmenopausal women, mostly not pretreated with systemic therapy and with ER positive or not determined ER status in tumor tissue, was <span><math><mtext>11</mtext><mtext>23</mtext></math></span> (48%; 95% confidence interval 37–59%) including 6 complete responses. The toxicity profile was similar to that of tamoxifen. It is concluded that toremifene is at least as active as tamoxifen in advanced breast cancer and that a randomized study between these two antiestrogens is indicated.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 3","pages":"Pages 233-234"},"PeriodicalIF":0.0,"publicationDate":"1990-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90013-I","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13296352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 21
Hormonal effects of toremifene in breast cancer patients 托瑞米芬对乳腺癌患者的激素影响
Journal of steroid biochemistry Pub Date : 1990-06-22 DOI: 10.1016/0022-4731(90)90018-N
I. Számel , B. Vincze , I. Hindy , S. Kerpel-Fronius , S. Eckhardt , J. Mäenpää , M. Grönroos , L. Kangas , H. Sundquist , A. Hajba
{"title":"Hormonal effects of toremifene in breast cancer patients","authors":"I. Számel ,&nbsp;B. Vincze ,&nbsp;I. Hindy ,&nbsp;S. Kerpel-Fronius ,&nbsp;S. Eckhardt ,&nbsp;J. Mäenpää ,&nbsp;M. Grönroos ,&nbsp;L. Kangas ,&nbsp;H. Sundquist ,&nbsp;A. Hajba","doi":"10.1016/0022-4731(90)90018-N","DOIUrl":"10.1016/0022-4731(90)90018-N","url":null,"abstract":"<div><p>The effect of toremifene treatment on the serum levels of sex steroids (estradiol, progesterone, testosterone), FSH, LH, prolactin, TSH, T3, T4 and SHBG was investigated. Basal prolactin level and the “prolactin reserve capacity” of the hypophysis was also studied by the TRH functional test. Steroid hormone receptors were detected in the patients where a tumor biopsy could be obtained. In a randomized trial patients were treated by 60 and 300 mg of toremifene per os, daily. Hormone levels were assayed prior to treatment and at the 2nd, 6th, 8th and 12th week of toremifene therapy. The hormonal effects of toremifene were the most marked at the 2nd and at the 8th week. Estradiol decreased continuously, SHBG increased slightly and the high initial value of basal prolactin level decreased. The TRH induced prolactin release was suppressed by toremifene after an 8-week period. No clinical response-related tendency was found.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 3","pages":"Pages 243-247"},"PeriodicalIF":0.0,"publicationDate":"1990-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90018-N","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13296357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 11
Proceedings of the Toremifene Symposium. Satellite symposium held at the UICC World Cancer Congress. Budapest, Hungary, 1986. 托雷米芬研讨会论文集。在UICC世界癌症大会举行的卫星研讨会。1986年，匈牙利布达佩斯。
Journal of steroid biochemistry Pub Date : 1990-06-22
{"title":"Proceedings of the Toremifene Symposium. Satellite symposium held at the UICC World Cancer Congress. Budapest, Hungary, 1986.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 3","pages":"187-262"},"PeriodicalIF":0.0,"publicationDate":"1990-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13296441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of toremifene on the activity of NK-cells in NZB/NZW mice 托瑞米芬对NZB/NZW小鼠nk细胞活性的影响
Journal of steroid biochemistry Pub Date : 1990-06-22 DOI: 10.1016/0022-4731(90)90006-E
Anni Wärri, Lauri Kangas
{"title":"Effect of toremifene on the activity of NK-cells in NZB/NZW mice","authors":"Anni Wärri,&nbsp;Lauri Kangas","doi":"10.1016/0022-4731(90)90006-E","DOIUrl":"10.1016/0022-4731(90)90006-E","url":null,"abstract":"<div><p>The effect of toremifene on NK-cells isolated from the spleen of NZB/NZW mice was studied in comparison to tamoxifen and estradiol. Unlike estradiol but like tamoxifen, toremifene did not influence the activity of NK-cells. Low doses (0.1 and 10.0 mg/kg) of toremifene did not suppress, but a high dose of toremifene and tamoxifen (50 mg/kg for 6 weeks) suppressed the stimulating effect of human interferon alpha on the cells.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 3","pages":"Pages 207-209"},"PeriodicalIF":0.0,"publicationDate":"1990-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90006-E","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13296445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Effect of toremifene on estrogen primed vaginal mucosa in postmenopausal women 托瑞米芬对绝经后女性雌激素引发阴道粘膜的影响
Journal of steroid biochemistry Pub Date : 1990-06-22 DOI: 10.1016/0022-4731(90)90009-H
J. Mäenpää , K.-O. Söderström , M. Grönrnroos , E. Taina , A. Hajba , L. Kangas
{"title":"Effect of toremifene on estrogen primed vaginal mucosa in postmenopausal women","authors":"J. Mäenpää ,&nbsp;K.-O. Söderström ,&nbsp;M. Grönrnroos ,&nbsp;E. Taina ,&nbsp;A. Hajba ,&nbsp;L. Kangas","doi":"10.1016/0022-4731(90)90009-H","DOIUrl":"10.1016/0022-4731(90)90009-H","url":null,"abstract":"<div><p>The antiestrogenic effect of 20 mg toremifene daily for 7 days and 68 mg for 5 days was studied in postmenopausal women volunteers primed for 7 days with estradiol valerate (2 mg daily orally) which was continued throughout the study. A control group received estrogen only and a reference group estrogen with 60 mg tamoxifen for 5 days.</p><p>No treatment opposed the action of the estrogen on the endometrium but both 68 mg toremifene and 60 mg tamoxifen statistically significantly decreased the maturity index of vaginal cells on day 13. A decrease was also evident on day 18 with 20 mg toremifene.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 3","pages":"Pages 221-223"},"PeriodicalIF":0.0,"publicationDate":"1990-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90009-H","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13296448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Phase II clinical study of high-dose toremifene in patients with advanced breast cancer 高剂量托瑞米芬治疗晚期乳腺癌的II期临床研究
Journal of steroid biochemistry Pub Date : 1990-06-22 DOI: 10.1016/0022-4731(90)90015-K
H. Modig , S. Borgström , I. Nilsson , G. Westman
{"title":"Phase II clinical study of high-dose toremifene in patients with advanced breast cancer","authors":"H. Modig ,&nbsp;S. Borgström ,&nbsp;I. Nilsson ,&nbsp;G. Westman","doi":"10.1016/0022-4731(90)90015-K","DOIUrl":"10.1016/0022-4731(90)90015-K","url":null,"abstract":"<div><p>Thirteen postmenopausal women with advanced local or metastatic breast cancer were treated with the antiestrogen toremifene at a daily dose of 200 mg. All patients had failed previous treatment with different types of endocrine therapy and/or cytotoxic drugs. Objective response was only seen in one patient. Treatment was usually well tolerated but in three cases the drug had to be withdrawn due to side effects.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 3","pages":"Pages 237-238"},"PeriodicalIF":0.0,"publicationDate":"1990-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0022-4731(90)90015-K","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13296354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
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