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Additive and synergistic antitumor effects with toremifene and interferons 托瑞米芬和干扰素的加性和协同抗肿瘤作用
Journal of steroid biochemistry Pub Date : 1990-06-22 Epub Date: 2003-02-05 DOI: 10.1016/0022-4731(90)90021-J
Lauri Kangas, Kari Cantell , Huub Schellekens
{"title":"Additive and synergistic antitumor effects with toremifene and interferons","authors":"Lauri Kangas,&nbsp;Kari Cantell ,&nbsp;Huub Schellekens","doi":"10.1016/0022-4731(90)90021-J","DOIUrl":"10.1016/0022-4731(90)90021-J","url":null,"abstract":"<div><p>MFC-7 cells were exposed to toremifene, human alpha and gamma interferons and combinations of them <em>in vitro</em>. Growth of the cells was followed by ATP bioluminescence method. Rats bearing DMBA-induced tumors were treated with toremifene, rat gamma Interferon and their combination daily for five weeks. The growth of the tumors was followed by palpation weekly.</p><p>Toremifene and interferons inhibited the growth of MCF-7 cells. Interferons alpha and gamma were additive; toremifene and interferons were additive or at the best synergistic.</p><p>Toremifene inhibited the growth of DMBA-induced tumors. Rat gamma interferon alone had no clear effect on the tumor growth. Combination of toremifene and gamma interferone was the most effective treatment and did not show any detectable toxicity.</p><p>Toremifene and interferons have interesting interactions. Clinical studies using the combination might be warranted.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 3","pages":"Pages 259-262"},"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)90021-J","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13296332","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: 5
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 Epub Date: 2003-02-05 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
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 Epub Date: 2003-02-05 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 Epub Date: 2003-02-05 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
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 Epub Date: 2003-02-05 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 Epub Date: 2003-02-05 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
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 Epub Date: 2003-02-05 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 Epub Date: 2003-02-05 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
Metabolism of toremifene in the rat 托瑞米芬在大鼠体内的代谢
Journal of steroid biochemistry Pub Date : 1990-06-22 Epub Date: 2003-02-05 DOI: 10.1016/0022-4731(90)90007-F
Hannu Sipilä, Lauri Kangas, Lauri Vuorilehto, Arm Kalapudas, Maire Eloranta, Marja Södervall, Reijo Toivola, Markku Anttila
{"title":"Metabolism of toremifene in the rat","authors":"Hannu Sipilä,&nbsp;Lauri Kangas,&nbsp;Lauri Vuorilehto,&nbsp;Arm Kalapudas,&nbsp;Maire Eloranta,&nbsp;Marja Södervall,&nbsp;Reijo Toivola,&nbsp;Markku Anttila","doi":"10.1016/0022-4731(90)90007-F","DOIUrl":"10.1016/0022-4731(90)90007-F","url":null,"abstract":"<div><p>Toremifene was labelled to a specific activity of about 20 μCi/mmol with tritium at positions 3 and 5 in the <em>para</em>-substituted phenyl ring. At these positions tritium is not eliminated within the metabolic pathways.</p><p>A mixture of unlabelled and labelled toremifene (5 or 10 mg/kg, 5 μCi/mg) was given i.v. or p.o. to Sprague-Dawley rats. The elimination of radioactivity was followed up by collecting urine and feces daily for 13 days. The elimination of toremifene which was similar after p.o. and i.v. administration took place mainly in the feces. About 70% of the total radioactivity was eliminated within 13 days, of this amount more than 90% in the feces. All applied radioactivity could be detected in three separate fractions according to the oxidative state of the side chain when counted by Berthold TLC Linear Analyzer. Each fraction was further separated into single metabolites by TLC or HPLC. Altogether 9 metabolites were identified and almost all methanol-extractable components were identified. The main metabolic pathways in the rat were 4-hydroxylation and <em>N</em>-demethylation. The side chain was further oxidized to alcohols and carboxylic acids. Small amounts of unchanged toremifene were found in the feces both after p.o. and i.v. administration indicating biliary secretion.</p></div>","PeriodicalId":17138,"journal":{"name":"Journal of steroid biochemistry","volume":"36 3","pages":"Pages 211-215"},"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)90007-F","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13296446","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: 30
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