Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixty postmenopausal patients with microscopically confirmed, progressive mammary carcinoma and local recurrence alone or in combination with distant metastases or with distant metastases only, not previously treated with cytostatics, were given tamoxifen (Nolvadex), 10 mg 3 times daily. The response rate in 37 evaluable patients was 48 per cent, with a median duration of the response of 26+ weeks. The effectiveness of the drug increased significantly with an increasing interval between primary treatment and the appearance of the first recurrence. No serious side effects occurred.
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PMID:Tamoxifen treatment of advanced breast carcinoma. 9 2

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 detection of specific hormone receptors in normal and tumor tissue has brought new insight into the mechanisms of action of hormones and anti-hormones. The Swiss Cooperative Cancer Study Group (SAKK) has evaluated the antitumor effect of the new antiestrogenic substance tamoxifen in metastatic breast cancer. 158 postmenopausal patients treated with 20 mg/d tamoxifen by mouth are evaluable at present time. Complete and good partial remissions were achieved in 39 patients (25%) largely with soft tissue but also lung and bone metastases. Tamoxifen was well tolerated and caused few serious complications such as thrombosis/pulmonary embolism and hypercalcemia. These results confirm already published experience with tamoxifen, which may replace the estrogens as the primary endocrine treatment in postmenopausal mammary carcinoma metastasizing to soft tissues, lung and bone.
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PMID:[Antiestrogens: a new endocrine treatment possibility in metastasizing breast neoplasms. Experiences of the Swiss Cooperative Cancer Study Group with tamoxifen]. 69 81

Forty mg daily of tamoxifen (Nolvadex) was administered orally to 89 patients with advanced soft tissue mammary carcinoma. At two months 43 per cent of the patients responded. At 6, 12 and 18 months, 42, 35 and 32 per cent, respectively, were still responding to therapy. The side effects were limited, fatique being the most frequent complaint. Oestrogen dependent side effects were not encountered. The therapeutic effect of tamoxifen is similar to that of oestrogen, but the side effects are less.
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PMID:Anti-oestrogen therapy of advanced mammary carcinoma. 103 56

Variations in DNA synthesis as measured by tritiated-thymidine autoradiography in mammary carcinoma before and during endocrine therapy were studied in patients treated for inoperable or locally recurrent mammary carcinoma. Tumor cells were collected by aspiration biopsy and immediately expelled into the incubating solution. Cell viability was assessed by staining unfixed cells with trypan blue and fixed cells with orecin. To assess viability tritiated-uridine incorporation was used in some experiments. The same cells were identified by each method. Bilateral oophorectomy was done in 4 patients. In the 1 case in which regression followed, a 5-fold decrease in DNA-synthesis was noted 1 week after oophorectomy but at 2 weeks no cells incoporated thymidine. In the 3 patients with tumor progression the fraction of labeled cells was unchanged. For antiestrogen therapy, Tamoxifen (Nolvadex) was used. Serial needle aspirates were collected from 38 patients who received 20 mg of Tamoxifen twice daily. Complete remission followed in 7, incomplete remission in 8, stationary disease in 7, and progression in 16. DNA synthesis fell to very low values after 1-3 weeks and remained low in the 7 cases with complete regression. Tumors showing partial regression showed diminished fractions of 5-phase cells (tritiated-thymidine-labeled cells) after 1-5 weeks. In 1 instance at 72 weeks the S-phase fraction of cells was higher than initial value. Tumor value remained stationary for 40 weeks and then increased. Antiestrogen therapy was stopped at 82 weeks. In those with progressive tumor growth there was high DNA synthesis. Between 20-30% of the cells were replicating DNA. None showed decrease in the fraction of S-phase cells, and 1 showed increase. For estrogen therapy, estradiol valepianate was given im every 2 weeks. Of the 3 patients who received estrogen therapy, 2 of the tumors responded and the DNA-synthesis rapidly decreased until none was measurable after 4 weeks. S-phase values prior to endocrine therapy showed no correlation with the therapeutic response. Tumors that responded showed a decrease in the proportion of S-phase cells during the first 3 weeks. In tumors responding to encocrine therapy the decrease in tritiated-thymidine incorporation was rapid and preceded reduction in tumor size. Data suggest that 2 aspirates should be studied before therapy and repeated after 2-4 weeks in order to include the minimal proportion of S-phase cells. The patients accepted the needle biopsies well. There were no growths of carcinoma at the puncture sites. About 5 weeks must elapse before tumor response can be assessed. Determining hormone receptors in surgically removed carcinoma specimens gives much more rapid indications as to possible response to endocrine therapy.
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PMID:3H-thymidine incorporation into mammary carcinoma cells obtained by needle aspiration before and during endocrine therapy. 106 73

Tamoxifen, a partial competitive antagonist to the estrogen receptor, is a potent inhibitor of the proliferation of experimental mammary carcinoma in the rat and is widely used clinically in the treatment of breast cancer. Blockade of estrogen receptors present on neoplastic cells represents the classic mechanism of action of tamoxifen, but the drug has a variety of other actions that may contribute to its antiproliferative properties. While it is recognized that estrogens play an important role in modulating pulsatile GH release, the effect of antagonists to sex steroid receptors on GH secretory dynamics has not previously been described. In the present study we examined the effect of tamoxifen on pulsatile GH secretion in free-moving adult male and female rats. The drug, when administered in a manner previously shown to be associated with antineoplastic activity, caused a marked suppression of the amplitude of spontaneous GH secretory bursts and significantly reduced mean 6-h plasma GH levels in both sexes compared to those in their respective peanut oil-injected controls. Inhibition of spontaneous GH pulses persisted for up to 7 weeks after tamoxifen administration in both sexes. Immunoneutralization of endogenous somatostatin in tamoxifen-treated male rats completely restored both GH pulse amplitude (121.6 +/- 9.5 vs. 62.5 +/- 13.5 ng/ml in tamoxifen-treated rats given normal sheep serum; P less than 0.02) and mean 6-h plasma GH levels (53.3 +/- 6.6 vs. 17.9 +/- 3.6 ng/ml in normal sheep serum-treated rats; P less than 0.01) to levels observed in our peanut oil-injected controls. These results demonstrate that 1) tamoxifen has potent inhibitory effects on pulsatile GH secretion; and 2) the blunting of GH pulse amplitude by tamoxifen is mediated at least in part by increased release of endogenous somatostatin. These findings motivate further investigation of the clinical significance of tamoxifen-induced suppression of GH secretion in relation to the antineoplastic activity of this commonly used drug.
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PMID:Tamoxifen attenuates pulsatile growth hormone secretion: mediation in part by somatostatin. 135 Jul 60

A 66-year-old postmenopausal woman presented in June 1991 with a giant ulcerated left breast tumor. She had discovered the tumor two years previously, but had never visited any medical institution. She was diagnosed as advanced breast cancer with multiple lung metastases, bone metastasis, and both supraclavicular lymph node metastases by physical examination, fine needle aspiration cytology, chest X-P, and bone scintigraphy. Incisional biopsy, performed to confirm the histological type of breast cancer and to evaluate estrogen and progesterone receptor (ER and PgR) status, revealed solid-tubular carcinoma. Both ER and PgR were highly positive at 322.6 and 228.0 fmol/mg protein, respectively. Therefore, endocrine therapy was chosen to treat this advanced breast cancer patient, although she had multiple organ metastases. Twenty mg of Tamoxifen a day was administered per os. After treatment with tamoxifen, the size of ulceration started to decreased and the dyspnea caused by multiple lung metastases was reduced. Eight weeks after, she showed partial response (PR) determined from the size of the ulceration and chest X-P. She has been maintaining PR for more than 9 months. Thus, Tamoxifen was shown to be very effective for this case of advanced breast cancer with multiple organ metastases.
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PMID:[A case of advanced breast cancer with multiple organ metastases successfully treated by tamoxifen]. 144 94

Tamoxifen, which is increasingly being used in breast cancer patients, has been associated with an elevated frequency of endometrial carcinoma. To our knowledge not a single case of uterine serous papillary carcinoma (USPC) has been documented during tamoxifen treatment. No conclusions as to a causal relationship are yet being made, but if it is due to tamoxifen, we should advise a strategy for prevention, because this subtype is not as curable as endometrioid carcinoma.
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PMID:An unusual type of endometrial cancer, related to tamoxifen? 145 92

The modification of estrogen and progesterone receptor status was prospectively studied in mammary carcinoma after short-term (7 days) administration of tamoxifen citrate (30 mg/day). Seventeen patients fulfilled the stringent criteria required for final evaluation. Tamoxifen was administered to them immediately prior to surgery and receptor status was studied on the surgical specimen. Estrogen receptor levels were significantly (p < 0.05) decreased after treatment, whereas progesterone receptors remained statistically unaltered, although they showed a tendency towards significant increase (p = 0.12). Following these results, short-term tamoxifen treatment seems inadequate for the induction of significant levels of progesterone receptors in mammary carcinoma.
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PMID:Variations in estrogen and progesterone receptor levels after short-term tamoxifen treatment in breast carcinoma. 146 79

N-Nitroso-N-methylurea (NMU) is an effective carcinogen for the induction of mammary carcinoma in the rat. Tamoxifen (TAM), used as a chemopreventive agent to reduce tumor incidence, has been well studied using this model. We have utilized the rat mammary carcinoma model to assess the effect of TAM on preneoplastic changes. Fifty-day-old virgin female Sprague-Dawley rats were randomized by weight and divided into the following five groups: Group 1, normal controls (n = 24); Group 2, TAM (n = 20); Group 3, NMU-short term (n = 24); Group 4, NMU-short term + TAM (n = 26); and Group 5, NMU-long term (n = 23). Seven weeks after the exposure to NMU, rats in Groups 1, 2, 3, and 4 were given injections of [3H]thymidine and sacrificed 4 h later for autoradiographic determination of thymidine labeling index (TLI). The rats from Group 5 were observed for 30 weeks after NMU exposure to confirm mammary tumor development. TLI in both terminal ducts and terminal end buds was modulated by treatment with TAM. Carcinogen administration induced higher TLI relative to the normal controls [18.3 +/- 1.8% (SD) versus 15.5 +/- 2.1%, P less than 0.001] in terminal end buds. The effect of carcinogen on TLI was also apparent in the terminal ducts (15.8 +/- 1.1% versus 9.5 +/- 1.1%, P less than 0.001). TAM administration was able to suppress both constitutive and NMU-induced TLI increases in terminal end buds (15.5 +/- 2.1% versus 2.8 +/- 1.1% and 18.3 +/- 1.8% versus 6.8 +/- 1.4%, respectively, P less than 0.001). Similar effects were observed in terminal ducts. In addition to its antiproliferative effect on nontransformed mammary tissue, TAM was effective in suppressing NMU-induced mammary tumor incidence and frequency. NMU-induced hyperproliferation is an intermediate stage in NMU carcinogenesis in the rat and is suppressed by TAM. Mammary epithelial hyperproliferation may provide a useful quantitative intermediate end point to evaluate chemopreventive efficacy.
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PMID:Effect of tamoxifen on preneoplastic cell proliferation in N-nitroso-N-methylurea-induced mammary carcinogenesis. 154 Sep 55


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