UMLS:C0006142 - FACTA Search

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Query: UMLS:C0006142 (breast cancer)
160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a combined phase I-II study, the hormonal effects of toremifene (TOR) were investigated in 30 patients. Half of the patients received continuous therapy of TOR 60 mg and half 300 mg of TOR orally daily. Serum concentrations of oestradiol (E2), progesterone (PROG), testosterone (TE), follicle stimulating hormone (FSH), luteinising hormone (LH), prolactin (PRL), human growth hormone (hGH) and sex hormone binding globulin (SHBG) were monitored prior to the treatment and at the second, sixth, eighth and twelfth weeks. The influence of TOR upon the hypothalamo-hypophyseal axis was investigated by the TRH (thyroid-stimulating hormone releasing hormone) functional test using 400 micrograms intravenous injection of TRH for stimulation of PRL secretion. The concentration of E2 decreased during the TOR therapy with 60 mg and 300 mg causing 82 and 71% decreases, respectively (non-significant). PRL was significantly (P < 0.001) suppressed. Both these effects reflect the anti-oestrogenic action of TOR. SHBG increased significantly at both doses of TOR, probably due to a direct oestrogen-like effect of TOR in the liver. TE decreased as a consequence of the elevated SHBG. The TRH-induced PRL release was suppressed by both doses of TOR. There were 17 and 27% reductions at 12 weeks in the 60 and 300 mg groups, respectively. Other hormones measured were not significantly affected by TOR. The hormonal effects of 60 and 300 mg doses of TOR did not differ significantly. Anti-oestrogenic (i.e. decrease of E2), and partially oestrogenic (i.e. increase of SHBG) properties as well as the antiprolactinic effects of TOR may have an overall beneficial effect in the clinical management of breast cancer patients.
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PMID:Influence of toremifene on the endocrine regulation in breast cancer patients. 815 88

We investigated the prevalence of Gs alpha gene mutations in growth hormone (GH) secreting pituitary adenomas from Japanese patients with acromegaly. Forty-five GH-secreting adenomas were examined for the presence of point mutations in codons 201 or 227 of the Gs alpha gene using the polymerase chain reaction-direct sequencing method and deoxyribonucleic acid extracted from paraffin-embedded tumor specimens. Mutation of codon 227 of the Gs alpha gene was not observed in any of the tumors, but a mis-sense mutation of codon 201 was identified in two tumors (4.4%). One lesion was a densely granulated GH cell adenoma in a patient with adenomatous goiter and breast cancer. The other was a mixed GH cell-prolactin cell adenoma in a patient with multiple endocrine neoplasia type 1 associated with parathyroid hyperplasia and a pancreatic islet cell tumor. The Gs alpha gene detected in parathyroid tissue and pancreatic tumor tissue was of the wild type in this second patient, and the mutation was specific to the pituitary tumor. These results suggest that point mutations of codons 201 or 227 of the Gs alpha gene may not be important mediators of oncogenesis for GH-secreting pituitary adenomas in Japan.
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PMID:Analysis of the Gs alpha gene in growth hormone-secreting pituitary adenomas by the polymerase chain reaction-direct sequencing method using paraffin-embedded tissues. 823 46

Various tumors of neuroendocrine origin that have amine precursor and decarboxylation (APUD) characteristics can be visualized in vivo after intravenous injection of the somatostatin analogue [123I-Tyr3]-octreotide. However, the relatively short effective half-life of this compound and the high background of radioactivity in the abdomen are drawbacks in its application. Therefore, an 111In-coupled somatostatin analogue ([111In-DTPA-D-Phe1]-octreotide) was developed. This analogue is excreted mainly via the kidneys, 90% of the dose being present in the urine 24 h after injection. Using 111In-octreotide scintigraphy, 7 out of 7 gastrinomas, 4 out of 7 insulinomas, 1 out of 1 glucagonoma, 3 out of 3 unclassified apudomas, but none out of 18 exocrine pancreatic carcinomas were visualized. Also, 19 out of 19 carcinoids, 15 out of 15 glomus tumors, 8 out of 12 medullary thyroid carcinomas, 6 out of 6 small cell lung carcinomas, 4 out of 4 growth hormone-producing and 6 out of 9 clinically nonfunctioning pituitary adenomas were visualized. Apart from APUD-cell-derived tumors, 111In-octreotide scintigraphy was also successfully applied to visualize breast cancer, lymphomas and granulomas. In 39 out of 50 patients with breast carcinoma, 10 out of 11 patients with non-Hodgkin lymphomas, 3 out of 3 patients with Hodgkin's disease, and 8 out of 8 patients with sarcoidosis, tumor sites accumulated radioactivity during octreotide scintigraphy. In a considerable number of patients with carcinoids and glomus tumors, but also in patients with granulomas and lymphomas, 111In-octreotide scintigraphy revealed more tumor sites than did conventional imaging techniques.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:111In-octreotide scintigraphy in oncology. 835 73

6 patients with advanced breast cancer who had failed first and second line endocrine therapies received bromocriptine (1.25-2.5 mg twice daily per os) and octreotide (Sandostatin) via a continuous subcutaneous infusion (200-400 micrograms/24 h) until disease progression. Pre-treatment 24-h profiles of serum lactogenic hormones and their response to standard provocative tests were established and repeated at 2 weeks, and 3 and 6 months (or at tumour progression). Immunoreactive prolactin (ir-PRL), growth hormone (ir-GH) and insulin-like growth factor I (IGF-I) were measured by radioimmunoassay and bioactive lactogenic hormone levels (BLH) were estimated using the Nb2 rat lymphoma cell bioassay. Before treatment all patients showed episodic secretion of ir-PRL, ir-GH and BLH and provocative stimuli resulted in a peak of ir-GH and BLH maximal between 60 and 90 min after injection but no change in ir-PRL. After 2 weeks of treatment, ir-PRL levels were reduced to below the limit of detection in all 6 patients. Peaks of ir-GH and BLH were still apparent, although much reduced. Immunoreactive PRL continued to be profoundly suppressed in 3 of the 4 patients who remained on treatment for 3 to 6 months. Small pulses of ir-GH were still detectable in these patients with which BLH was, again, well correlated. After 2 weeks of treatment, serum IGF-I levels were reduced by 9-54% of the pretreatment values and generally remained suppressed throughout treatment. Clinically, 4 patients did not show disease progression for periods of up to 6 months and side-effects were minimal.
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PMID:Serum immunoreactive and bioactive lactogenic hormones in advanced breast cancer patients treated with bromocriptine and octreotide. 842 85

Loss of heterozygosity (LOH) of markers for chromosome 17 is the most frequent genetic change observed in breast cancer to date. To assess whether the location of several candidate target genes is compatible with patterns of allele losses in the individual tumors, we examined the LOH status of chromosome 17 in 109 primary breast tumors with 15 polymorphic DNA markers (three for 17p and 12 for 17q). Allelic imbalance (AI) at 17q was observed in 44 of the 97 informative cases. A significant correlation was found between AI at the long arm and AI at the short arm of chromosome 17. The patterns of AI on 17q in the tumors differed and were highly complex in some cases. A number of tumors showed AI distal to the growth hormone locus, whereas others showed AI exclusively proximal of this marker. These results indicate that there are at least two different regions of allele loss on 17q.
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PMID:Allele loss patterns on chromosome 17q in 109 breast carcinomas indicate at least two distinct target regions. 843 62

Tamoxifen, a partial antagonist to the estrogen receptor, is widely used in the treatment of breast cancer and is currently being evaluated as a breast cancer preventative agent in large-scale clinical trials. Recent clinical research has demonstrated that tamoxifen administration is associated with a reduction of serum insulin-like growth factor I (IGF-I) concentration. We demonstrate here that tamoxifen, when administered in an in vivo experimental system previously used to demonstrate its cytostatic effect on breast cancer cell proliferation, inhibits the expression of the IGF-I gene in common target organs for breast cancer metastasis. Furthermore, while our prior experimental studies have demonstrated an inhibitory effect of tamoxifen on growth hormone output, we show here for the first time that the suppression of IGF-I gene expression associated with tamoxifen administration is in part a consequence of a pituitary-independent action of the drug. Because IGF-I is a potent mitogen for breast cancer cells, this newly described activity of tamoxifen may contribute to its antineoplastic properties, particularly with regard to inhibition of metastasis seen both in animal models and clinically.
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PMID:In vivo inhibition of insulin-like growth factor I gene expression by tamoxifen. 846 86

Melatonin (aMT) appears to be a potentially important oncostatic substance that can block the mitogenic effects of tumour-promoting hormones and growth factors such as oestradiol and epidermal growth factor, in vitro. In the present study, we examined the possibility that aMT would also inhibit the stimulatory effects of the tumour-promoter prolactin (PRL) on MCF-7 and ZR75-1 human breast cancer cell (HBC) growth under 5% charcoal-stripped fetal bovine serum culture conditions. Human PRL (10-100 ng ml-1) stimulated the rate of MCF-7 and ZR-75-1 HBC growth up to 2-fold above that of untreated controls. Melatonin, at concentrations between 10(-12) M and 10(-5)M, diminished and at physiological levels completely abolished PRL's mitogenic activity, but had no effect on growth in the absence of PRL. The mitogenic effects of human growth hormone (hGH), a PRL-related hormone, and also of several monoclonal antibodies (MAbs) against the PRL receptor (PRLR), were also abrogated by physiological concentrations of aMT. Additionally, aMT blocked the enhancement of MAb mitogenic activity induced by a second 'cross-linking' antibody (CLA). These findings indicate that aMT interrupts the PRLR-mediated growth signal in HBC and suggest that the oncostatic activity of aMT may also be linked with an antagonism of PRL's actions.
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PMID:Melatonin blocks the stimulatory effects of prolactin on human breast cancer cell growth in culture. 851 56

The role of progestins in the pathogenesis of breast cancer in women remains controversial. To advance this discussion, we report the demonstration and localization of progestin-induced biosynthesis of growth hormone (GH) in canine mammary gland tissue. Nontumorous mammary tissues and tumors, both benign and malignant, were obtained from private household dogs. Immunoreactive GH was localized in mammary epithelial cells and correlated with the presence of GH mRNA. Local synthesis of GH was also proven immunoelectron microscopically by demonstrating GH-containing secretory granules. Cellular GH production in nontumorous tissues was more extensive during the progesterone-dominated luteal phase of the ovarian cycle or during exposure to synthetic progestins than during anestrus. GH was also associated with areas of hyperplastic mammary epithelium, which may indicate that locally produced GH enhances proliferation, acting in an autocrine and/or paracrine manner. In 41 of 44 tumors, GH was present. Of 3 GH-negative tumor samples, 2 were from progestin-depleted, castrated bitches. In nonmalignant mammary tissues, GH production is stimulated by progesterone and synthetic progestins interacting with progesterone receptors. In some progesterone-receptor-negative malignant tumors, GH expression was found, indicating loss of this control. Progestin-induced GH probably participates in the cyclic development of the mammary gland but may promote mammary tumorigenesis by stimulating proliferation of susceptible, and sometimes transformed, mammary epithelial cells.
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PMID:Expression of growth hormone in canine mammary tissue and mammary tumors. Evidence for a potential autocrine/paracrine stimulatory loop. 906 Aug 40

Hormones such as melatonin whose serum concentrations vary seasonally have been previously implicated in the growth of breast cancer. The present study was undertaken to identify possible seasonal variation in a range of mammotrophic hormones which could exert a chronobiologic influence in women with breast tumours. Fifteen premenopausal women with a history of previous breast cancer (BC subjects) and 10 control women underwent 2-hourly serum sampling for 24 h at both summer and winter solstice for measurement of melatonin, growth hormone (GH), insulin-like growth factor-I (IGF-I), cortisol, prolactin and thyrotrophin (TSH). Hormone secretion at the different seasons was compared by measuring the area under the 24 h serum hormone concentration x time curves and by time series analysis of summer-to-winter differences in hormone concentration. Control women had significantly higher GH and IGF-I levels in summer compared to winter and significantly higher cortisol secretion in winter than summer. In contrast, BC women had no significant seasonal difference in IGF-I concentrations and had a reversal of the normal seasonal pattern of melatonin secretion, although seasonal changes in GH production were similar to controls. Prolactin and TSH showed no significant summer/winter variation in either group. Thus, seasonal variations in hormone secretion seen in normal women were, with exception of GH, absent or reversed in women with a previous history of breast cancer. As a result these individuals may be exposed to an asynchronous hormonal stimulus which could influence tumour growth. These changes could reflect a constitutional abnormality in BC women or may have been induced by the previous breast tumour.
Breast Cancer Res Treat 1997 Jan
PMID:Seasonal variation in the secretion of mammotrophic hormones in normal women and women with previous breast cancer. 911 14

The primary nutritionally linked diseases are coronary heart disease, stroke and cancers of the stomach, colon, pancreas, prostate, breast, ovary, and endometrium. Dietary fats operate through a promoting mechanism. An S-shaped dose-response curve with a threshold has been demonstrated in models of breast and colon cancer in which the standard Western fat intake of 40% of energy yields a high level of promotion, and reduction of fat to 10% to 20% of energy (the traditional Japanese fat intake) has a low promoting action. In models of breast and colon cancer, saturated fats such as beef fat or lard, and monounsaturated oils, such as olive oil, display only a weak promoting effect, with the incidence of induced tumors being similar at intake levels of 40% and 10% of energy. On the other hand, the n-6-polyunsaturated oils display a strong promoting effect. Such findings may have a parallel in the low but definitely increasing slope of postmenopausal breast cancer incidence in the past 30 years as the American public decreased saturated fat intake to avoid heart disease and increased use of the n-6-polyunsaturated oils. Mechanisms underlying the cancer-promoting effect in the colon stem from increased hepatic production of bile acids, which are transferred to the intestinal tract via the bile. Ingestion of 40% fat calories yields higher concentrations of bile acids in the colon than lower levels of dietary fat ingestion. Cancer in the mammary gland is promoted through higher concentrations of fats and phospholipids in the gland as well as increased levels of estrogen secondary to production by the ovary and other endocrine tissues that, in turn, affect the generation of pituitary hormones such as prolactin and growth hormone. The n-3-fats, as found in fish and fish oils, have a pronounced inhibitory effect in models of colon and breast cancer, presumably through their shifting of prostaglandin metabolism to the generation of prostaglandins, which lower cell proliferation potential and, thus, decrease promotional effects. The role of dietary fat as a promoter can be modified by other nutritional components. Finally, one of the best pieces of evidence for an enhancing effect of many dietary fats in the nutritionally linked cancers is the current increase in the incidence of these diseases in Japan as the nutritional habits of people in that country become more Westernized.
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PMID:Dietary fat and risk of chronic disease: mechanistic insights from experimental studies. 921 63

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