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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 464 (1986), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7217
    Keywords: Vitamin D3 receptor ; mammary tumor growth ; epidermal growth factor ; calcium metabolism ; paracrine growth factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The biological role of 1,25(OH)2D3 in controlling Ca++ homeostasis in the body has been identified and widely investigated for a long time. More recently its effect in regulating cell proliferation or differentiated activity was described in a variety of normal and malignant cells. The present study was carried out to investigate the different aspects and biological mechanisms of this activity and to determine if the use of 1,25(OH)2D3 in the treatment of breast cancer patients could be considered. It is found that 1,25(OH)2D3 reduces the proliferation of MCF-7 and BT-20 cell lines regardless of their sex steroid receptor status. This effect is related to the concentration, from 10−12 M to 10−8 M. Its amplitude is less in other cell lines, but it opposes the EGF-induced increase of proliferation. It is observed that the proliferation rate of MCF-7 and BT-20 cells is increased when these tumor cells are cocultured with fibroblasts derived from breast tumor biopsies and that 1,25(OH)2D3 reverses this process. Moreover, experiments on DMBA induced mammary tumors in Sprague Dawley rats found that 1,25(OH)2D3 given at non toxic doses reduces significantly the tumor proliferation. These data showed that 1,25(OH)2D3 at low doses is effective on the proliferation of BT-20 and MCF-7 cells and on the paracrine growth stimulatory effect observed in the presence of fibroblasts. They suggest that 1,25(OH)2D3 or related synthetic molecules which are less active on Ca++ metabolism could be useful in the treatment of breast cancer patients.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 3 (1983), S. 345-353 
    ISSN: 1573-7217
    Keywords: estrogen receptor ; progesterone receptor ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Estradiol receptor alone or estradiol and progesterone receptors (ER, PgR) have been measured in tumors from 307 women who were treated for primary breast adenocarcinoma. Patients received adjuvant therapy in relation to tumor stage independently of receptor status. Over a relatively short follow-up, more recurrences are recorded in patients with ER + tumors, but at 7 years the same proportion of recurrences are registered in both groups of patients whose tumors were ER + or ER −. Patients whose tumors were processed for both ER and PgR (148 cases) have now been evaluated after 5 years follow-up. Among 56 patients with PgR + tumors 5 recurred, versus 22/92 in the PgR − group. 21/87 patients who had 1 to 4 invaded nodes at the time of surgery relapsed: 17/54 had PgR − tumors versus 4/33 PgR +. 6 recurrences were recorded in the 61 patients with negative nodes: 5 of them occurred in patients with PgR − tumors. In addition, recurrences observed in patients with negative receptor status occurred after a shorter disease-free interval. Analysis of the incidence of recurrences in relation to the combined ER/PgR status in patients who did not receive adjuvant therapy suggests that tumor PgR content is a more significant criterion than ER for longterm prognosis.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7217
    Keywords: EGF-R mRNA ; PCR ; estrogen receptor ; breast cancer biopsies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is well known that breast cancer cells can synthesize and secrete various growth factors that are able to stimulate tumor growth through autocrine and/or paracrine mechanisms. EGF is one of these growth factors involved in normal breast epithelial development and tumor proliferation. EGF and TGFα (EGF-like peptide) are produced in variable amounts and both bind to the EGF receptor (EGF-R). Previous investigation in the laboratory measuring free and occupied EGF-R sites by differential ligand binding assays had demonstrated that non-occupied and total binding sites were present in 54 and 90% of 216 breast tumor biopsies respectively. EGF-R appeared to be totally masked by endogenous ligand in 40 and 21% of estrogen receptor positive and negative tumors respectively. The aim of the present study was to check by a molecular method the expression of the EGF-R gene. The PCR method was applied to 94 tumor samples of the previous series. Total RNA was treated with 0.5 units of Rnase-free Dnase/mg of RNA to remove any contaminating DNA. We simultaneously reverse transcribed and amplified another transcript (β-actin) as an internal standard. Both signals were present in 88 of the 94 samples while the presence of EGF-R was detected in 74 of them when assessed by radioligand assay. The findings indicate that 93% of the tumors analysed in this series expressed EGF-R mRNA, in agreement with our previous data on occupied EGF-R sites, i.e. two-fold more than by using the standard binding assay. No significant correlation was observed between the expression of the EGF-R gene and the estrogen receptor content.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7217
    Keywords: breast cancer ; cell interactions ; 1,25‐dihydroxyvitamin D3 ; fibroblast ; normal epithelial cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mesenchymal‐epithelial interactions are of paramount importance during normal and tumoral breast developments. We have investigated the paracrine growth regulation of normal and tumoral breast epithelial cells by fibroblasts derived from normal or pathological breast tissues. In some cases, breast cancer MCF‐7 cells or normal epithelial cells in primary culture were cocultured with fibroblasts in a Transwell system allowing diffusible factor exchanges. Alternatively, conditioned medium produced by fibroblast cultures was added to epithelial cell cultures. Fibroblasts were shown to stimulate the proliferation of normal and carcinoma cells through paracrine mechanisms. However, the paracrine exchanges appeared to be different in normal versus tumoral breast epithelial cell growth regulation. Moreover, vitamin D‐related compounds that have been proposed as anti‐tumoral drugs were studied for their ability to affect normal and tumoral mammary epithelial cell proliferation and to interfere with the growth‐regulatory activity of fibroblasts. Whereas vitamin D compounds inhibited MCF‐7 cell growth, they led to a marked stimulation of the proliferation of normal mammary epithelial cells. Moreover, it was shown that the vitamin D analog EB 1089 can block the mitogenic effect of fibroblast‐conditioned medium on tumoral but not normal breast epithelial cells. The differential effects of vitamin D compounds on cell proliferation provide further data in favor of the different behaviours of normal and tumoral mammary epithelial cells. The potential therapeutic use of vitamin D derivatives in the treatment of breast cancer is supported by these results but their growth‐stimulatory properties on normal epithelial cells cannot be overlooked.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-7217
    Keywords: occupied EGF receptor ; ligand dissociation ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The epidermal growth factor (EGF) is one of several growth factors involved in normal breast epithelial development and tumor proliferation. EGF and EGF-like peptide TGFα bind and activate the same membrane receptor protein. This receptor (EGF-R) has been recently studied in breast tumor biopsies and its detectability reported as a prognostic indicator. However, normal and tumor tissue themselves produce EGF and related peptides in variable amount. This suggests that the standard measurement of EGF-R by binding assay should reflect only the number of non-occupied receptor sites. Based on this observation, the presence of occupied sites (EGF-R2) has been assessed in 216 human mammary tumor biopsies simultaneously with the direct measurement of non occupied EGF receptor sites (EGF-R1) and the results compared to estrogen and progesterone receptor status (ER, PGR). EGF-R1 and EGF-R2 were evaluated by 2 separate (125I) EGF binding assays performed on 2 aliquots of tumor crude membrane fraction, the first one directly, the other after dissociation of the endogenously bound ligand. The validity of the method has been assessed on membrane fractions prepared from human placenta. It is shown that the dissociation does not modify the binding dissociation constant. ER and PGR were measured by the dextran coated charcoal method. Results 〉 10 fmol/mg of membrane or cytosol protein were considered as positive. It is found that EGF-R1 and EGF-R2 are detectable in 54 and 90% of the cases, indicating that EGF-R is masked by endogenous ligand in 36% of the tumors. The mean incidence of EGF-R1 positivity is significantly higher in ER-(66%) than in ER+ tumors (49%) while EGF-R2 is detectable in 90% of tumors regardless of ER status. These data suggest that EGF-like peptides are locally produced in the majority of breast tumors. The positive relation between the presence of ER and the total occupancy of EGF-R sites could be in favor of their control by estrogens.
    Type of Medium: Electronic Resource
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