Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00345 (ICI)
 5,388 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of human mammary tumour 800 x g supernatants with [3H]oestradiol after preincubation for 10 min at 0 degrees C with 10 mM dihydrolipoic acid resulted in metabolism of oestradiol. This was noted in 12 malignant tumours, 8 of which contained measurable oestrogen receptor levels. In 2 benign tumours lacking measurable levels of receptor, dihydrolipoic acid pretreatment had no effect. This metabolism was further stimulated by pretreatment with NAD, NADP and the anti-oestrogen Tamoxifen (ICI 46,474). When incubations were carried out in an O2 atmosphere using oxygenated buffers, the effect was suppressed.
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PMID:Metabolism of oestradiol by human mammary tumour 800 x g supernatants pretreated with dihydrolipoic acid. 4 33

Tamoxifen (ICI 46,474) has been shown to possess anti-tumour properties in the dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinoma model. During tamoxifen therapy the binding of [3H]oestradiol in vivo to uterine (P less than 0-001), vaginal (P less than 0 X 01) and tumour (P less than 0-001) tissues was significantly reduced. Tamoxifen therapy was without effect on the binding of [3H]oestradiol in heart tissue. The determination of specific oestrogen-binding components in vitro was significantly reduced (P less than 0-01) in tumours from tamoxifen-treated rats and tamoxifen inhibited the binding of [3H]oestradiol to 8S oestrogen-binding components, derived from rat uteri and DMBA-induced tumours, in vitro.
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PMID:Tamoxifen as an anti-tumour agent: effect on oestrogen binding. 17 95

The effect of prolactin in supporting the growth of 7, 12-dimethylbenz(a)anthracene-induced mammary tumor in adult female Sprague-Dawley rats was investigated when estrogen receptors were blocked by the nonsteroidal antiestrogen, Tamoxifen, ICI 46,474. Following an oophorectomy-induced remission, perphenazine, which stimulates endogenous prolactin release, was able to restore tumor growth whether or not Tamoxifen was added. A second course of perphenazine treatment, instituted after the tumors were allowed to shrink, was again effective in stimulating tumor growth. After a regression in tumor size induced by oophorectomy and daily administration of Tamoxifen, perphenazine was able to restore original tumor size despite continued treatment with Tamoxifen. In intact rats, after regression was obtained by daily administration of Tamoxifen and the prolactin inhibitor, lergotrile mesylate, perphenazine induced tumor growth when the latter was discontinued, even though Tamoxifen was continued for 50 days. Estrogen receptors measured at the time of maximum stimulation by perphenazine were undetectable. On the other hand, estradiol did not stimulate tumor growth when serum prolactin was depressed to undetectable levels by lergotrile. These results indicate that prolactin supports the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor and that estrogen receptors are not required under these conditions.
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PMID:Predominant role of prolactin in stimulating the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor. 19 Nov 82

86 postmenopausal women with disseminated breast cancer have been treated orally with 30 mg of Tamoxifen per day (ICI 46474, Nolvadex) for periods of 2 months or more. The overall responders were 28/86 (32.5%) with a median remission duration of 9 months. In 30 patients already shown to be resistant to cytotoxic chemotherapy. Tamoxifen was used as first hormonal agent; the remission rate in this group was 12/30 (40%), while it was 28.5% (16/56) in the others who had already received different hormonal treatments. In 6 early menopausal cases, the treatment had to be stopped for a dangerous "worsening syndrome". Other side effects were trivial. In 28/35 cases (80%), we have found the reappearance of a pattern of estrogenic activity in vaginal smears during treatment. Hence a "simil-estrogen", more than an "anti-estrogen" mechanism of action is postulated and a selection of patients for treatment in the "mid postmenopausal age" is recommended.
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PMID:Tamoxifen in disseminated breast cancer. 60 76

Tamoxifen (ICI 46474), an antiestrogen, was given to 89 selected patients with stage IV breast cancer at a dose of 20 mg orally every 12 hours. Forty-seven percent of the patients had objective tumor regression averaging 11+ months with 25 of 42 women still in remission. In the first 39 patients where the minimum follow-up period is 16 months the average duration of remission is more than 15 months with 8 of 19 patients still in remission. These results are approaching those of surgical hypophysectomy, where, in our experience the average remission lasts about 18 months. Thus, Tamoxifen is a highly effective antitumor agent and is probably the initial treatment of choice for women with hormone responsive breast cancer. Antiestrogen induced objective remissions in 5 of 19 patients who had previously responded to surgical hypophysectomy, and 5 additional patients showed no progression of disease lasting 15+ months. Estradiol and estrone were detectable in the serum of these patients whereas, prolactin and growth hormone were not detectable. Thus, antiestrogen can induce remissions in some patients in the absence of the pituitary gland, and this constitutes additional palliation and provides evidence that estrogens can directly stimulate tumor growth. Four of 7 patients who obtained remissions from Tamoxifen obtained further improvement from hypophysectomy, and 1 of 8 patients who failed to benefit from antiestrogen improved after hypophysectomy. These results suggest that prolactin and growth hormone may also play a role in stimulating tumor growth in some patients.
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PMID:Treatment of breast cancer with antiestrogen: approach to medical hypophysectomy? 61 66

This paper reviews the antiestrogenic and antitumor properties of tamoxifen (NSC-180973; ICI-46474) in the rat. In classic tests for antiestrogenic activity, tamoxifen inhibits the actions of estradiol in the rat uterus and vagina. At the cellular level, tamoxifen inhibits estrogen binding to cytoplasmic estrogen receptors, but although estrogen-receptor units are translocated to the nucleus DNA synthesis does not occur. It is suggested that tamoxifen competes for estrogen receptors in the cytoplasm and the false messenger units block the nuclear acceptors which are normally activated by estradiol-estrogen receptor complexes thereby provoking DNA synthesis. Tamoxifen inhibits the growth of some 7.12-dimethylbenz(a)anthracene-induced rat mammary tumors whereas others continue to grow. Estrogen-stimulated rises in plasma prolactin are only partially inhibited by tamoxifen although at the tumor level, tamoxifen completely blocks estrogen binding. There is a linear correlation (P less than 0.01) between estrogen-receptor levels in tumor biopsies before therapy and tumor responses to 3 weeks of tamoxifen treatment (50 mug/day) i.e., tumors with low levels of estrogen receptors do not respond to therapy whereas tumors with higher levels of estrogen receptors regress. It is suggested that tamoxifen antagonizes the actions of estrogen at the tumor level by blocking the estrogen-receptor mechanism thereby producing tumor regression. Therefore, estrogen-receptor measurements in tumor biopsies before therapy may be a useful predictive test for the tumor response to tamoxifen treatment.
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PMID:Antiestrogenic and antitumor properties of tamoxifen in laboratory animals. 82 17

The human breast cancer cell line MCF-7 contains estrogen receptors and responds to estrogens with an increase in growth rate and to antiestrogens with a decrease in growth rate. Estrogen stimulation of cell proliferation is concomitant with an increase in the synthesis and secretion of three proteins with mol. wt 52 kDa, 61 kDa and 66 kDa and a decrease in the synthesis and secretion of a 42 kDa protein. The antiestrogen ICI 164,384 has a complete estrogen antagonistic effect on the synthesis of these secreted proteins, whereas the antiestrogen tamoxifen has an agonistic effect on the synthesis and secretion of the 52 kDa protein. We believe that the above mentioned estrogen regulated secreted proteins are either directly or indirectly involved in control of cell proliferation, and the less pronounced inhibitory effect of tamoxifen on cell proliferation compared to ICI 164,384 may be due to agonistic effects of tamoxifen. A tamoxifen resistant variant of the MCF-7 cell line, the AL-1 subline, can be growth inhibited by ICI 164,384, although a higher concentration is needed to inhibit the AL-1 cells compared to the parent MCF-7 cells. Tamoxifen has no effect on secreted proteins from the AL-1 cells, whereas ICI 164,384 has a complete estrogen antagonistic effect on secreted proteins, indicating that the mechanisms by which estrogens and antiestrogens influence cell proliferation may be via up and down regulation of secreted proteins with growth regulatory functions.
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PMID:Effect of estrogen and antiestrogens on cell proliferation and synthesis of secreted proteins in the human breast cancer cell line MCF-7 and a tamoxifen resistant variant subline, AL-1. 162 27

Twenty-nine Nigerian women with advanced breast carcinoma treated with Tamoxifen (Nolvadex ICI) at a dosage of 20 mg twice daily have been reviewed. Eight of 26 evaluable patients had objective response (31%). No statistically significant association was found between response rate and menopausal status, previous chemotherapy or disease free interval. The drug was well tolerated with a low incidence of side effects. This study suggests that Tamoxifen is a useful drug in the adjuvant management of patients with advanced breast carcinoma in Nigeria.
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PMID:Tamoxifen in the management of advanced breast carcinoma in Nigerian women. 170 86

Results of adjuvant hormone therapy with Tamoxifen, an antioestrogenic substance, have been discussed. 82 patients in 2 groups who were diagnosed with metastatic mammary carcinoma received Tamoxifen (ICI) and Tamoxifen (Ebewe) orally in a dosage of 20 to 40 mg/day. 43% of the patients in group A (Tamoxifen, ICI) experienced complete or partial remission of the metastases. In group B (Tamoxifen, Ebewe), this result was achieved in 54% of cases. The better results were due to the fact that the disease was not so advanced in the group B patients and they were also longer in the menopause. Thus in terms of efficacy, the preparations are identical. Severe side effects due to the therapy were not observed.
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PMID:[The treatment of metastasizing breast carcinoma using antiestrogens]. 192 78

A case of recurrent retroperitoneal desmoid tumor successfully treated with tamoxifen (Nolvadex tablets, ICI Pharma, Division of ICI Americas, Wilmington, DE) is reported. The patient presented late in her second pregnancy with a large retroperitoneal pelvic desmoid tumor that was treated with surgical excision and megestrol acetate. When the tumor recurred 12 months later, it was again treated with surgery, this time followed by radiation therapy. The desmoid tumor quickly recurred. The patient was then treated with tamoxifen, resulting in a complete tumor regression that has remained stable for 27 months. Tamoxifen should be considered as first-line therapy in recurrent desmoid tumors.
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PMID:A recurrent pelvic desmoid tumor successfully treated with tamoxifen. 199 11


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