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)

A human ovarian adenocarcinoma cell line (PE04) has been established as a xenograft in nude mice. In vitro, this cell line is estrogen receptor (ER)-positive and its growth is stimulated by 17 beta-estradiol at concentrations between 10(-12) and 10(-6) M. When xenografted, PE04 cells remain ER-positive and also possess progesterone receptors (PR); treatment with 17 beta-estradiol reduces the concentration of ER and increases levels of PR. Growth of the xenograft is reduced in ovariectomized animals while implantation of estrogen pellets also results in growth inhibition. Similar treatment with estrogen does not inhibit the ER-negative HOX 60 ovarian xenograft, and stimulates growth of the ER-positive ZR-75-I breast carcinoma xenograft. Serum measurements of 17 beta-estradiol confirm that ovariectomy reduces the level of 17 beta-estradiol while implantation of estrogen pellets results in raised levels of the hormone. Tamoxifen inhibits growth of the PE04 xenograft but not that of the HOX 60 xenograft, consistent with ER status. These results indicate that ER-positive PE04 ovarian cancer cells are sensitive to 17 beta-estradiol in vivo but that the response may be of a different type from the in vitro response. This lends further support to the concept that ovarian cancer may be hormone-sensitive and potentially responsive to endocrine therapy.
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PMID:Contrasting effects of 17 beta-estradiol on the growth of human ovarian carcinoma cells in vitro and in vivo. 837 30

Steroid sex hormones cause immediate changes in the endometrium. The histologic effect depends on the hormone, the potency, dosage, and the host receptor status. Oral contraceptives (OCs) containing a low-dose, low-potency progesterone and low-dose estrogen stop proliferation of the glands during the 1st few cycles and the glands are straight and unevenly distributed, with considerable stroma between them. The minimal secretory features of the glands disappear with longterm use of these OCs, resulting in complete atrophy of the glands and of the stroma. These OCs also cause decidual reaction without spiral arterioles and stromal granulocytes. OCs with high potency progesterone cause distinct hyperplasia of the endometrial stroma and vessels, atrophy of the glands, and stromal myomatous nodules. Ovulation induction therapy consists of various combinations of some drugs (clomid, human menopausal gonadotropins, gonadotropin-releasing hormone, and human chorionic gonadotropin). This therapy accelerates secretory changes in the stroma, resulting in enhancement of the endometrial maturation process. It makes it difficult to differentiate between glands displaying early secretory changes and an edematous, decidualized stroma. Hormone replacement therapy using estrogens and progesterone cause different histologic patterns, including stromal hyperplasia and decidual transformation, glandular and adenomatous hyperplasia, glandular metaplasia, proliferative and secretory endometrium, atrophic endometrium, and any of these with endometrial atrophy. Progesterone therapy for endometrial hyperplasia and neoplasia produces secretory changes of the endometrium, such as subnuclear vacuole, decidual reaction, and squamoid "morules." These changes can result in residual carcinoma. Tamoxifen therapy for breast cancer is linked with endometrial hyperplasia, polyps, adenomyosis, adenomatous hyperplasia, and adenocarcinoma.
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PMID:Effects of hormone therapy on the endometrium. 842 60

Tamoxifen is an antioestrogen drug used widely in the management of oestrogen-dependent metastatic breast carcinoma. A number of ocular complications have been described secondary to tamoxifen therapy. We report two patients, one of whom had superior ophthalmic vein thrombosis and the other who had painful proptosis and acute angle-closure glaucoma with choroidal detachment secondary to tamoxifen therapy, both of which have not been reported earlier. In both patients the signs and symptoms resolved rapidly after the discontinuation of tamoxifen therapy. Awareness of the ocular toxicity of tamoxifen is essential as prompt withdrawal can result in resolution of most of the complications.
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PMID:Ocular toxicity of tamoxifen. 852 65

Attempts were made to correlate growth effects induced by oestradiol and tamoxifen with the hormonal regulation of c-erbB-2 protein in experiments in vivo. We report here the responsiveness of four xenotransplanted oestrogen-receptor(ER)-positive and four ER-negative human mammary carcinomas to oestradiol and tamoxifen. Oestradiol in a dose of 0.5 mg/kg significantly increased the growth of the ER-positive mammary carcinomas 3366, MCF-7, 4134 and 4049, but not the ER-negative tumours 4000, 4296 and MT-3. However, within the group of the ER-negative breast carcinomas the tumour 4151 ES deviates from this growth behaviour, as we could prove an estrogen induced growth. The stimulation of tumour growth by oestradiol was always accompanied by a down-regulation of c-erbB-2 protein both in the ER-positive mammary carcinomas and in the ER-negative mammary carcinoma 4151 ES. Tamoxifen significantly inhibited the growth of the ER/PR-positive mammary carcinomas 3366 and MCF-7 but not the ER-positive/PR-negative mammary carcinomas 4049 and 4134. In the group of ER-negative mammary carcinomas only the growth of the oestrogen-responsive tumour 4151 ES was significantly inhibited by tamoxifen. The inhibition of tumour growth by tamoxifen was correlated with a reversion of the oestradiol-induced down-regulation of c-erbB-2, also in the ER-negative/oestradiol-responsive mammary carcinoma 4151 ES. From our results we hypothesize that the oestrogen-dependent growth of ER-negative breast carcinoma 4151 ES could also be correlated with the oestradiol-regulated expression of c-erbB-2 protein.
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PMID:Relation of oestradiol-mediated growth stimulation with the expression of c-erbB-2 protein in xenotransplanted oestradiol-receptor-positive and -negative breast carcinomas. 854 87

Lobular carcinomas have a distinct natural history with a better response to endocrine therapy and a higher incidence of local recurrence and are more often bilateral. The cytological diagnosis of lobular carcinoma permits a discriminating therapeutic approach with pre-operative Tamoxifen, more generous resection margins, and assessment of the contralateral breast. The cytological features of lobular cancer however are not well defined and the low cell yield from such neoplasms can result in a high false negative rate. To determine whether we could improve the pre-operative diagnosis, we reviewed the cytological features of 112 lobular carcinomas. They had small uniform sized nuclei with irregular outlines and inconspicuous nucleoli. The degree of dissociation was similar to duct carcinomas and the incidence of inadequate aspirates was no higher. We found no features that confidently diagnosed lobular cancer or its sub-types. However, using a combination of features, typing of lobular cancer on aspirated material is possible and should be attempted.
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PMID:Lobular carcinoma of the breast: cytological features supporting the diagnosis of lobular cancer. 857 77

The aromatase inhibitor vorozole dose-dependently inhibited the growth of dimethylbenz(a) anthracene (DMBA)-induced mammary carcinoma in the rat. An oral dose of 5 mg/kg per day brought about growth inhibition and reduction of tumor multiplicity similar to that produced by ovariectomy. Tamoxifen (8 mg/kg per day) also reduced tumor growth, albeit to a lesser extent than did ovariectomy. Concomitant administration of varying doses of tamoxifen with the fully effective dose of vorozole (5 mg/kg per day) tended to be less effective than ovariectomy of vorozole alone. This is likely to be due to the estrogen-agonistic effects of tamoxifen. Combination of tamoxifen with the partially effective dose of vorozole (1 mg/kg per day) gave results comparable with those obtained for either of the compounds used in monotherapy. Combining tamoxifen with a marginally active low dose of vorozole (0.2 mg/kg per day) resulted in a minor additional growth inhibition as compared with that obtained with this dose of vorozole alone. Sequential treatment with tamoxifen (8 mg/kg per day) for 42 days and vorozole (5 mg/kg per day) for 42 days, and vice-versa, was performed with a drug-free interval of 14 days between treatments. Tumors regressing under vorozole therapy relapsed when subsequently treated with tamoxifen. In contrast, vorozole further reduced tumor volumes in rats previously treated with tamoxifen. Furthermore, monotherapy with tamoxifen as well as the two sequential tamoxifen-vorozole treatment schedules were in most cases less effective than vorozole monotherapy in inhibiting both tumor growth and tumor multiplicity. Although extrapolation of these findings in cycling animals to the clinical situation, involving postmenopausal women, is not straightforward, these results warrant further studies in preclinical models. Moreover, clinical trials comparing the most effective aromatase inhibitors with tamoxifen in previously untreated postmenopausal patients with breast cancer may also be warranted.
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PMID:Effects of combined and sequential treatment with tamoxifen and the aromatase inhibitor vorozole on 7,12-dimethylbenz(a) anthracene-induced mammary carcinoma in the rat. 860 47

Tamoxifen is an oestrogen antagonist with partial agonistic effects that is used extensively in the treatment of mammary carcinoma. We report a case of an 80 year old woman who was operated on for carcinoma of the mammary gland and developed endometrial carcinoma after ten years of tamoxifen treatment. Tamoxifen has been noted for its reportedly low incidence of side effects. Since 1985, however, several reports have associated tamoxifen with higher risk of endometrial carcinoma. We also review the relevant literature published during the last decade.
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PMID:[Tamoxifen and endometrial cancer. A case report]. 871 96

Receptors group (ER+, PgR+) in post-menopausal and pre-menopausal patients with ductal and lobular infiltrating mammary cancer clinical stage III and poorly differentiated histological assessment was studied. Levels of (ER+, PgR+) were correlated to endocrine therapy response (Tamoxifen) after 5 years of its administration. Both pre and post-menopausal patients with infiltrating ductal carcinoma, the (RE+, RPg+) tumour content, the mean values were 52 +/- 8, 53 +/- 11 fmol/mg protein and 111 +/- 20, 36 +/- 7 fmol/mg protein, respectively. With regard to lobular carcinoma, the (RE+, RPg+) tumour content, the mean value was 109 +/- 28, 46 +/- 12 fmol/mg protein in pre-menopausal patients, whereas it was 287 +/- 60, 66 +/- 18 fmol/mg protein in post-menopausal patients. The tumour was considered (ER+, PgR+) when specific binding was than 10 fmol/mg protein. In both ductal and lobular carcinoma the mean (ER+) concentrations are significantly different between the post and pre-menopausal patients, while the mean (PgR+) concentrations are significantly different in post-menopausal women. After five years of treatment with tamoxifen, survival analysis of patients with ductal infiltrating and lobular infiltrating carcinoma revealed a very strong correlation between levels of receptor group (ER+, PgR+) and their response to endocrine therapy.
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PMID:[Receptor (ER, PgR) levels as prognostic factors in the endocrine therapy of pre- and post-menopausal patients with stage III infiltrative ductal and lobular cancer of the breast]. 872 91

Tamoxifen has been widely used in the treatment of breast cancer. The effects on the uterus include epithelial metaplasia, hyperplasia and even carcinoma. Transvaginal sonography has been used for visualization of endometrial changes during tamoxifen treatment. However, its use has disclosed that the drug may cause cystic changes in the subendometrial zone without epithelial pathology. Therefore, other sonographic techniques have been suggested for the evaluation of the patient receiving tamoxifen treatment, among them saline contrast hysterosonography and endometrial blood flow studies. These new modalities provide us with tools to evaluate the effect of tamoxifen on the endometrium, prior to the decision to perform invasive procedures.
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PMID:Tamoxifen and the uterus: an old drug tested by new modalities. 877 8

Tamoxifen as sole initial therapy is gaining importance in the management of post-menopausal breast cancer patients. Age oestrogen (ER) and progesterone (PR) receptor status are accurately considered to select patients for hormonal treatment. However, additional markers are needed. By immunohistochemistry (IHC), we studied tumour expression of ER, PR, pS2, c-erbB-2 and glutathione S-transferase pi (GST pi) on initial core biopsies of 208 post-menopausal patients with a non-metastatic invasive ductal carcinoma, treated by neoadjuvant tamoxifen therapy. A good response to tamoxifen was defined as tumoral regression > or = 50% (110 patients). Relationship between response and age, tumour size, T, N, histological grade, ER and PR contents evaluated by radioimmunoassay, ER, PR, pS2, c-erbB-2 and GST pi expression evaluated by IHC were studied. Univariate and multivariate analysis showed that tumoral regression was linked only to pS2 (P = 0.004) and ER (P = 0.018) IHC expression. According to the immunohistochemical profile, three groups could be defined: pS2- and ER-positive tumours, pS2- or ER-positive tumours and pS2- and ER-negative tumours with response rates of 60%, 45% and 8% respectively. Although prospective studies are needed to confirm these results, we conclude that pS2 and ER immunohistochemical status are useful tools for predicting tumour regression with neoadjuvant tamoxifen in post-menopausal breast carcinoma patients.
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PMID:pS2 protein: a marker improving prediction of response to neoadjuvant tamoxifen in post-menopausal breast cancer patients. 885 85


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