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Query: UMLS:C0006826 (cancer)
 1,092,456 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.
Cancer Lett 1977 Mar
PMID:Metabolism of oestradiol by human mammary tumour 800 x g supernatants pretreated with dihydrolipoic acid. 4 33

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.
Cancer Res 1977 Apr
PMID:Predominant role of prolactin in stimulating the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor. 19 Nov 82

Tamoxifen is a synthetic nonsteroidal drug with antiestrogenic properties. This report describes the response of patients with metastatic breast cancer to tamoxifen and correlates clinical responses with tumor tissue content of cytoplasmic estrogen binding proteins (EBPs) and other biochemical parameters. Ages of patients ranged from 27 to 82 years. 7 patients were premenopausal, 63 postmenopausal, and 2 had recent endocrine ablaetion. Prior hormone therapy, radiotherapy, or chemotherapy ahd been given to all patients. Tamoxifen was given at a dose of 20 mg orally for a minimum of 4 weeks and continued if an objective remission was shown. Before therapy a biopsy specimen was taken for determination of EBP and for specific enzyme activities. Another biopsy specimen was taken for at least 8 weeks after therapy. A total of 72 patients were treated for at least 4 weeks. The overall response rate was 38%. Most frequent responses were in the over-70 age group. The median duration of response has been 9.5 months. Bony involvement responded to therapy in 21 of 28 patients. No responses were shown in 6 patients with liver metastases. Only 1 of 18 patients who had previous chemotherapy responded. Of 31 who had no prior chemotherapy, 73% achieved a remission. There was a 44% correlation between patients with a positive EBP assay and response to therapy, but none in EBP-negative patients. In this study 20 of 28 patients had normal arylsulfatase B/DNA ratios in their tumor tissue and 11 of the 20 responded to tamoxifen therapy. Patients who responded most favorably to therapy had normal G-6-PD activities. It is concluded that tamoxifen therapy may cancel the need for ablative surgery in postmenopausal patients with positive EBPs and who have had a prior response to additive hormonal treatment.
Cancer Treat Rep 1976 Oct
PMID:Therapeutic use of tamoxifen in advanced breast cancer: correlation with biochemical parameters. 19 Nov 85

ZR-75-1, a human breast cancer cell line, has been grown in hormone-supplemented medium without serum. The factors required for optimal growth include 17beta-estradiol, insulin, transferrin, dexamethasone, and L-triiodothyronine. If estradiol, insulin, or L-triiodothyronine is omitted, cells cease division within 7 days, but viability is retained for at least 14 days. Omission of transferrin leads to cell death within 7 days. The cells have been continuously maintained in this environment without morphological alteration or cessation of growth for more than 5 months. Addition of the anti-estrogen, Tamoxifen (10(-6) M), inhibited cells below the growth rate seen when estradiol was omitted from the medium, even when Tamoxifen was added 4 days and two medium changes after the removal of estradiol from the medium, thus suggesting an action of Tamoxifen which may be independent of competition with estradiol. The availability of a human breast cancer cell line that can be propagated in hormone-supplemented medium without serum should aid in the study of the mechanisms by which hormones effect cell growth.
Cancer Res 1978 Nov
PMID:Growth of a human breast cancer cell line in serum-free hormone-supplemented medium. 21 80

Tamoxifen 1 is a triphenylethlene oestrogen antagonist which has partial oestrogen agonist activity in some species. Most therapeutic trials with tamoxifen have involved postmenopausal women with advanced brease cancer, about 25 to 60% of patients showing same improvement while receiving treatment (usually 20 or 40mg daily); however- poorly defined assessment criteria in some studies make it difficult to compare the results of different authors. 7 to 18% of patients have had complete clinical remissions lasting for a few months to several years. Although few comparative studies with other treatments have been done, it nevertheless appears that tamoxifen is at least as effective as standard oestrogen or androgen therapy in postmenopausal women, while producing a lower incidence of troublesome adverse effects. In the only comparison with a cytotoxic treatment regimen, the response rates with tamoxifen and cytotoxic therapy were similar (41% versus 50%) in patients who were more than 5 years postmenopausal and had primarily soft-tissue involvement; but in patients who were within 2 to 5 years of their last menstrual period cytotoxic treatment was more effective. Similarly, most authors have reported a higher response rate with tamoxifen in women several years postmenopausal than in those more recently postmenopausal. Tumours which contain receptors respond more often to tamoxifen than those which do not. Administering tamoxifen concomitantly with other chemotherapeutic agents such as cytotoxic drugs appears to increase the response rate, but as might be expected also increases the incidence of adverse reactions. When used alone tamoxifen has been relatively well tolerated in all studies, the overall withdrawal rate due to side-effects being less than 3%.
 ...
PMID:Tamoxifen: a review of its pharmacological properties and therapeutic use in the treatment of breast cancer. 35 63

The antiestrogen Tamoxifen (T), given orally to 113 patients with stage IV breast cancer, induced objective remission in 50%. Duration of remission in the first 39 patients, with minimum 27 months follow up, is 18 + months; these results are equal to those of surgical hypophysectomy. T prolonged survival in responders. Older age, previous response to endocrine therapy and positive estrogen receptors predicted response to T. T was effective in hypophysectomized patients in whom serum growth hormone and prolactin were undetectable, but serum ostrogens were present in low amount, suggesting a direct stimulatory effect of estrogens at the tumor level. Hypophysectomy induced further palliation after treatment with T, indicating that pituitary hormones may also play a role in the growth of some human breast cancers. Side effects from T were minimal. T is the initial treatment of choice for postmenopausal women with hormone responsive stage IV breast cancer.
Cancer 1979 Feb
PMID:Antihormone treatment of stage IV breast cancer. 42 Nov 71

Transsphenoidal hypophysectomy was performed in 212 consecutive patients with metastatic breast cancer: 11 died within 30 days, two of surgical complications and nine of advanced metastatic disease. Two patients were unevaluable because of inadequate follow-up in one and simultaneous radiation treatment in the other. Of 199 evaluable patients 42% had an objective remission. Duration of remission averaged 18+ months with 10 out of 84 patients still in remission. Presence of estrogen receptors in the tumor significantly predicted response to hypophysectomy. Of 156 patients in whom completeness of hypophysectomy was assessed, 128 were thought to have a complete removal as shown by the fact that their growth hormone and prolactin were undetectable after stimulation with arginine or chlorpromazine, respectively. Of 26 patients in whom TRH test was performed, TSH and prolactin were undetectable in 20. Of 23 patients where autopsy was performed only six had microscopic pituitary tissue remaining. Hypophysectomy induced remission in eight of 15 patients who had previously responded and then relapsed to the antiestrogen Tamoxifen and in four of 17 who had failed. Conversely, antiestrogen therapy induced remission in six of 26 patients who had previously responded to hypophysectomy and in whom serum estrogens were present in small amount. These data indicate that both gonadal and pituitary hormones play a role in the growth of some human breast cancers.
Cancer 1979 Dec
PMID:Transsphenoidal hypophysectomy in breast cancer: evidence for an individual role of pituitary and gonadal hormones in supporting tumor growth. 50 1

Tamoxifen is a specific estrogen antagonist used in the treatment of breast cancer. In a previous study, corneal and retinal changes were reported in four patients receiving high-dose tamoxifen therapy for greater than 1 year. Nineteen patients treated with tamoxifen for periods of 3 months to 4 years at normal dose levels have been studied and no ocular changes attributable to the drug were observed.
Cancer Treat Rep
PMID:Ocular assessment of patients treated with tamoxifen. 52 17

Seventy-eight advanced breast cancer patients, most of whom had had prior treatment, were treated with the synthetic antiestogen tamoxifen. The overall objective response rate was 27% (21/78). An additional 19% (15/78) showed disease stabilization. Sixty-seven percent (14/21) of the responses were in soft tissue sites, 24% (5/21) on bony sites and one each occurred in liver and nodular lung disease. Forty percent of patients with soft-tissue disease alone responded, while less than 10% of patients with visceral disease showed responses in visceral sites. The response rate was 28% among patients with a known positive estrogen receptor (ER) assay. It was 21% among patients who had previously received cytotoxic drugs. Toxicity was mild and was seen in nausea and vomiting, hot flushes and vaginal bleeding, and occasional myelosuppression. One patient was withdrawn from the study because of a rash. In two patients the disease flared, once with concomitant hypercalcemia. Tamoxifen is a useful agent for advanced breast cancer even in some patients with visceral disease.
Cancer Chemother Pharmacol 1979
PMID:Phase-II trial of tamoxifen in advanced breat cancer. 53 27

Tamoxifen has been used as a chemotherapeutic agent with no serious side effects noted. Four patients receiving high-dose tamoxifen for greater than 1 year have demonstrated similar retinal changes. Three of the four patients had a significant decrease in visual acuity as the result of a retinopathy, primarily affecting the region about the macula accompanied by macular edema. In addition, three of the four patients had unusual corneal changes. These findings suggest that the corneal and retinal changes are the result of a toxic effect of tamoxifen when used in the doses and duration described.
Cancer Treat Rep 1978 Mar
PMID:Tamoxifen retinopathy. 64 93


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