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

We evaluated height as a potential risk factor for breast cancer in a case-control study of 747 young women diagnosed with invasive breast cancer before age 46 years and 961 control subjects recruited by random digit dialing. We found that total height attained did not affect a woman's risk of the disease. The age when a women reached her maximum height, however, was a risk factor for breast cancer. There was a trend of decreasing risk of breast cancer in relation to increasing age of height attainment, culminating in a 30% reduction in the risk of breast cancer for women who reached their maximum height when they were 18 years or older compared with women who reached their maximum height when they were 13 years old or less (odds ratio = 0.7; 95% confidence interval = 0.5-1.0). Although the age at menarche was correlated with the age at maximum height, the effect of age at maximum height persisted after adjustment for age at menarche. Previous studies have reported that age at menarche is an important determinant of risk, but this study indicates that age when maximum height is reached may be another, and possibly more important, landmark of puberty that is related to breast cancer risk. The physiologic basis for this claim may lie in the influence on breast development of exposure to growth hormone and insulin-like growth factor during puberty, and on a decreased time between the end of puberty and a woman's first livebirth, both of which are believed to affect a woman's risk of breast cancer.
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PMID:Age when maximum height is reached as a risk factor for breast cancer among young U.S. women. 927 Sep 59

In MCF-7 breast cancer cells, insulin-like growth factor-1 (IGF-1) increased the calcium-permeability of the cells by activating a voltage-independent calcium-permeable channel. IGF-1 also induced oscillatory elevation of cytoplasmic free calcium concentration in these cells. An anti-allergic compound, tranilast, reduced the calcium-permeability augmented by IGF-1 in a dose-dependent manner and blocked the oscillatory elevation of cytoplasmic free calcium concentration. Tranilast did not affect early intracellular signals activated by IGF-1, including receptor autophosphorylation, activations of Ras, mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Tranilast inhibited increases in [3H]-thymidine incorporation, DNA content and cell number induced by IGF-1. The ID50 for [3H]-thymidine incorporation and DNA content were about 10 microM. The inhibitory effect of tranilast was reversible, and cell viability was not affected. Treatment with tranilast increased the number of cells in the G1 phase suggesting that this compound induced G1 arrest. Tranilast also reduced the phosphorylation of the retinoblastoma protein. These results indicate that tranilast inhibits the IGF-1-induced cell growth in MCF-7 cells by blocking calcium entry.
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PMID:Inhibition of proliferation of MCF-7 breast cancer cells by a blocker of Ca(2+)-permeable channel. 929 25

Insulin-like growth factors (IGFs) are known to have potent antiapoptotic activity. The antiestrogen ICI 182,780 (ICI) is a potent inhibitor of MCF7 human breast cancer cell growth and has recently been reported to act as an antiproliferative agent in part via upregulation of expression of insulin-like growth factor binding proteins (IGFBPs) -3 and -5, which attenuate the bioactivity of IGFs in many experimental systems. We show here that ICI and IGFBP-3 induce apoptosis in MCF7 cells. Treatment of MCF7 cells with 10 nM ICI or 36 nM recombinant human IGFBP. 3 for 72 hours increased apoptosis approximately 3.5-fold relative to control as quantitated by a cell death ELISA which measures DNA fragmentation. Long R3 IGF-I, an IGF-I analogue with greatly reduced affinity for IGFBPs yet similar affinity for IGF-I receptors, was a more potent inhibitor of IGFBP-3-induced and ICI-induced apoptosis than IGF-I. These results suggest that IGFBP-3 enhances apoptosis by reducing bioavailability of ligands for the IGF-I receptor and suggest that modulation of IGFBP-3 expression by ICI contributes to apoptosis induced by this compound. More generally, the data suggest that IGFBPs are regulators of apoptosis.
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PMID:Insulin-like growth factor binding protein-3 induces apoptosis in MCF7 breast cancer cells. 929 28

Toremifene is a chlorinated tamoxifen analogue that is indicated for the treatment of postmenopausal hormone-dependent breast cancer. It competes with estradiol for estrogen receptors and has growth-inhibitory effects on MCF-7 breast cancer cells. At concentrations < 10(-6) mol/L, this growth inhibition can be reversed by estradiol, but at higher concentrations toremifene is cytotoxic. In dimethylbenzanthracene (DMBA)-induced mammary cancer in rats, toremifene has been shown to decrease the number of new tumours and to inhibit the growth of existing tumours. Toremifene causes growth inhibition by suppressing mitosis and inducing apoptosis. The mechanism by which these events occur may involve the induction of transforming growth factor-beta 1 and inhibition of insulin-like growth factor-1 (mecasermin). Toremifene is primarily an antiestrogen, but it has some estrogen agonist properties in postmenopausal women. The latter are reflected by the fall in luteinising hormone and follicle-stimulating hormone levels and the rise in sex hormone-binding globulin levels that are associated with its use in most women. After estrogen priming, toremifene 68mg administered orally has been found to exert a similar antiestrogenic effect on the vaginal epithelium in postmenopausal women as tamoxifen 60mg. The half-life of toremifene in plasma is 5 days, and the drug is > 99% bound to plasma proteins. The main metabolites of toremifene are N-demethyl-toremifene and deaminohydroxy-toremifene. Altered liver, but not kidney, function affects the pharmacokinetics of toremifene. Toremifene 60mg daily is as effective as tamoxifen 20mg daily in the treatment of postmenopausal hormone-dependent breast cancer, producing a response in about 50% of patients. Soft tissue and visceral metastases respond better to toremifene than bone metastases. Most of the adverse effects of toremifene are related to its activity at estrogen receptors and include hot flashes, vaginal discharge and nausea. Although toremifene decreases antithrombin III levels slightly, the incidence of thromboembolic complications is low. Thus far, no carcinogenic effects have been noted in humans, and preclinical data are mostly reassuring. Toremifene has favourable effects on serum lipids, and thus has potential in preventing coronary heart disease. Although toremifene is somewhat more expensive to use than tamoxifen, toremifene is an effective and well tolerated alternative to tamoxifen in the treatment of postmenopausal women with hormone-dependent breast cancer. No formal pharmacoeconomic comparisons of toremifene and tamoxifen have yet been published. Toremifene is potentially safer than tamoxifen in relation to carcinogenic effects and effects on serum lipids.
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PMID:Toremifene in postmenopausal breast cancer. Efficacy, safety and cost. 934 56

hGrb10alpha (previously named Grb-IR) is a Src-homology 2 domain-containing protein that binds with high affinity to the tyrosine-phosphorylated insulin receptor and insulin-like growth factor-1 receptor. At least two isoforms of human Grb10, (hGrb10alpha and hGrb10beta), which differ in the pleckstrin homology (PH) domain and the N-terminal sequence, have previously been identified in insulin target tissues such as human skeletal muscle and fat cells. Here we report the cloning of the third isoform of the hGrb10 family (hGrb10gamma) from human skeletal muscle and its localization to human chromosome 7. We have also determined the human chromosome localization of Grb7 to 17q21-q22 and Grb14 to chromosome 2. hGrb10gamma contains an intact PH domain and an N-terminal sequence that is present in hGrb10alpha but absent in hGrb10beta. RNase protection assays and Western blot analysis showed that hGrb10alpha and hGrb10gamma are differentially expressed in insulin target cells including skeletal muscle, liver, and adipocyte cells. hGrb10gamma is also expressed in HeLa cells and various breast cancer cell lines. The protein bound with high affinity to the insulin receptor in cells, and the interaction was dependent on the tyrosine phosphorylation of the receptor. hGrb10gamma also underwent insulin-stimulated membrane translocation and serine phosphorylation. hGrb10gamma phosphorylation was inhibited by PD98059, a specific inhibitor of mitogen-activated protein kinase kinase, and wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase. Taken together, our data suggest that hGrb10 isoforms are potential downstream signaling components of the insulin receptor tyrosine kinase and that the PH domain may play an important role in the involvement of these isoforms in signal transduction pathways initiated by insulin and other growth factors.
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PMID:Cloning, chromosome localization, expression, and characterization of an Src homology 2 and pleckstrin homology domain-containing insulin receptor binding protein hGrb10gamma. 936 Sep 86

The insulin-like growth factor binding proteins (IGFBPs) are a family of seven structurally homologous proteins that bind insulin-like growth factor 1 (IGF-I) and IGF-II with high affinity, thereby modu-lating the actions of IGFs. Several lines of recent evidence from various cell systems have suggested that IGFBPs, especially IGFBP-3, may play more active, IGF-independent, roles in growth regulation of cancer cells. In support of this hypothesis, the author has recently shown that IGFBP-3 binds specifically and with high affinity to the surface of various cell types and directly inhibits monolayer growth of these cells in an IGF-independent manner, presumably by specific interaction with cell membrane proteins that function as an IGFBP-3 receptor. The author's current studies demonstrate that a new class of IGFBP, IGFBP-7, constitutes a low affinity member of the IGFBP family, but primarily functions as a modulator of cell growth in an IGF-independent manner, similar to the action observed with IGFBP-3 in breast cancer cells. The author's studies on the mechanisms of action of the low affinity IGFBPs will provide insight into the IGF-independent actions of the classical high affinity IGFBPs and their impact on cancer cell growth.
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PMID:IGFBPs and neoplastic models. New concepts for roles of IGFBPs in regulation of cancer cell growth. 944 45

Over the past decade, impressive antineoplastic activity of somatostatin analogs has been demonstrated in many tumor models. More recent research has provided information regarding mechanisms underlying the antiproliferative and apoptosis-inducing actions of these compounds. These include both 'direct' mechanisms that are sequellae of binding of somatostatin analogs to somatostatin receptors present on neoplastic cells and 'indirect' mechanisms related to effects of somatostatin analogs on the host. The upregulation of intracellular tyrosine phosphatase activity triggered by binding of ligands to the type II somatostatin receptor has received considerable attention as a direct mechanism, not only because this activity is the converse of the tyrosine kinase activity associated with many peptide mitogen receptors, but also because the type II somatostatin receptor is frequently expressed by common human neoplasms, including breast cancer. The potential importance of indirect mechanisms of action of somatostatin analogs, such as alterations in host insulin-like growth factor physiology, is emphasized by the in vivo antineoplastic activity of these compounds against somatostatin receptor-negative neoplasms. Clinical efficacy and a favorable toxicity profile of somatostatin analogs in the treatment of relatively uncommon conditions such as acromegaly and neuroendocrine tumors have already been demonstrated. Preclinical data now are sufficient to justify controlled clinical trials in breast, prostate, and pancreatic cancer. The development of monthly depot formulations will facilitate the clinical evaluation of somatostatin analogs for these and other indications.
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PMID:Mechanisms of antineoplastic action of somatostatin analogs. 945 37

Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels were measured in two groups of postmenopausal women with advanced breast cancer, who received the aromatase inhibitor letrozole 0.5 or 2.5 mg p.o. once daily. Blood samples were obtained from 15 patients in each dose group at baseline, and one and three months after starting therapy. Circulating IGF-I and IGFBP-3 concentrations were determined by means of radioimmunoassay. In both dosage groups a statistically significant increase in the IGF-I levels was observed during three months of letrozole treatment (P=0.003). In addition, the multiple testing procedure yielded in the whole patient population a significant result in the comparison between mean IGF-I values after three months of therapy and those observed at baseline (P=0.004), the estimated average increase being of 24%. No significant result was obtained in the analysis for the dose effect (P=0.077) and for the time x dose interaction (P=0.208). Circulating IGFBP-3 levels did not appear to be affected by letrozole treatment in either of the dose groups. This is the first report concerning the short-term effects of letrozole on components of the IGF system in breast cancer patients; further investigations are warranted in order to confirm these preliminary data.
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PMID:The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels. 945 92

The effects of two vitamin D analogues, EB1089 and CB1093, on insulin-like growth factor binding protein (IGFBP) expression have been examined in MCF-7 and Hs578T human breast cancer cell lines. Both vitamin D analogues inhibited IGF-1 stimulated growth of MCF-7 cells and enhanced the production of IGFBP-3 as determined by Western-ligand blotting. Recombinant human IGFBP-3 inhibited the growth of MCF-7 cells over the concentration range 1-235 ng/ml. Hs578T cells were unresponsive to the mitogenic effects of IGF-1 but growth was inhibited by the two vitamin D analogues. Treatment of Hs578T cells with EB1089 and CB1093 (10 nM) as well as 100 nM 9-cis retinoic acid (9-cis RA) or all-trans retinoic acid (ATRA) was associated with increased accumulation of IGFBP-3 in conditioned medium. Furthermore, cotreatment of Hs578T cells with EB1089 and 9-cis RA led to augmented effects on both inhibition of cell growth and IGFBP-3 accumulation in conditioned medium as assessed by Western ligand blotting and radioimmunoassay. These findings suggest a role for IGFBP-3 in the growth inhibitory effects of vitamin D analogues.
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PMID:Growth inhibition of both MCF-7 and Hs578T human breast cancer cell lines by vitamin D analogues is associated with increased expression of insulin-like growth factor binding protein-3. 951 92

Local environmental signals regulate the growth and development of both normal and malignant breast epithelium. Members of the insulin-like growth factor (IGF) family likely influence both of these processes. The localization of IGF2 to stroma specifically surrounding malignant breast epithelium indicates that this growth factor may play a critical role in the genesis or maintenance of this transformed phenotype. Recent studies have sought to understand the mechanism by which IGF2 expressing fibroblasts are localized to the periphery of malignant breast cancer cells. In addition, the consequences of the expression of IGF-signaling components likely expand beyond their direct effects on mitogenesis. Indirect effects predominantly associated with the IGF2 receptor could also influence the invasive potential of breast tumor cells.
Breast Cancer Res Treat 1998 Feb
PMID:Paracrine/autocrine regulation of breast cancer by the insulin-like growth factors. 951 78


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