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  • 1
    ISSN: 1573-7217
    Keywords: biological markers ; breast cancer ; two-dimensional electrophoresis ; estrogen receptor ; progesterone receptor ; polypeptides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Postmitochondrial and cytosolic polypeptides were extracted from human breast tumors and non-malignant breast tissue and analyzed using high resolution two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Approximately 800–1000 postmitochondrial and 600–800 silver stained cytosolic polypeptides were detected over the pH range of 4.8 to 7.5 and molecular weight range of 18–120 kDa. The 2D-PAGE patterns of polypeptides from normal and malignant tissue were very similar, although both qualitative and quantitative polypeptide differences were noted. Six cytosolic polypeptides (pI/molecular weight × 10−3) 5.20/80 kDa, 5.75/43, 6.25/40, 5.43/35, 5.45/34.5, 5.50/34 and 6.15/24 were expressed only in malignant tissues. One constitutive polypeptide, 7.25/52, was not detected in any of the malignant tissue samples. Quantitatively, marked differences in spot density were noted in polypeptides localized mainly in the molecular weight ranges of 22–40 kDa and pI ranges of 5.65–7.00. A general increase in polypeptide expression was noted in malignant tissues as compared to normal. Twenty-two polypeptides were significantly and consistently increased in tumor samples while only one polypeptide was decreased. One polypeptide, p24 (6.15/24) was expressed in greatest concentrations in tumors which also expressed the greatest estrogen receptor content. Expression of p24 was markedly reduced in normal tissue and malignant tissues expressing low levels of estrogen and progesterone receptors.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7217
    Keywords: INT2 ; ERBB2 ; amplification ; expression ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relationships of INT2 and ERBB2 amplification and of ERBB2 overexpression in primary breast tumors to prognostic factors, recurrence, and survival have generated considerable controversy. The rationale for this study is that long-term, recurrence-free survival is a more direct criterion for testing the validity of a tumor marker than correlation either with prognostic factors or with short-term recurrence and survival. We examined the association of recurrence with INT2 and ERBB2 amplification and ERBB2 expression by comparing primary breast tumors from patients surviving without recurrence for ≥ 8.5 years after diagnosis. the LTS group, to tumors from patients recurring within two years, the RR group. The RR (N = 63) and LTS (N = 61) samples were coded and examined for amplification by Southern blotting and for expression by immunohistochemistry. Comparison between the RR and LTS groups demonstrated that INT2 amplification was associated with a significantly (P = 0.018) higher (5.6-fold) risk of recurrence, an association that remained significant after controlling for lymph node (LN), tumor size (TS), and histograde (HG) status. ERBB2 amplification and expression were not associated with a higher recurrence risk. Survival analyses within the RR group, however, demonstrated significantly shorter survival time among cases with than without ERBB2 amplification (P = 0.018, median survival 16 vs 25 months), or ERBB2 expression (P = 0.019, median survival 15 vs 25 months), but not INT2 amplification. Univariate Cox proportional hazards regression models also demonstrated significantly shorter survival among cases with ERBB2 amplification (P = 0.016) or expression (P = 0.049), that remained significant in multivariate analyses (P = 0.022) for ERBB2 amplification. These results indicate a significant positive association between INT2 amplification and risk for tumor recurrence in the RR as compared to the LTS group. The relationship of ERBB2 amplification or overexpression to patient outcome is more complex. ERBB2 amplification and expression have a significant relationship with shorter survival among patients recurrent within two years, but their occurrence in tumors from women surviving without recurrence for ≥ 8.5 years suggests that ERBB2 status is not predictive of shorter survival for all breast cancers.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 22 (1992), S. 129-132 
    ISSN: 1573-7217
    Keywords: tamoxifen ; breast cancer ; body weight
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Changes in body weight have been studied in 92 consecutive patients with primary breast cancer from the time of initial diagnosis and treatment. Sixty patients receiving tamoxifen were compared with 32 controls receiving no hormone treatment. Weight gain was seen in both groups, but was greater in the group receiving tamoxifen. Premenopausal women receiving tamoxifen had greater weight gain than postmenopausal women on tamoxifen therapy.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7217
    Keywords: bone scans ; breast cancer ; follow-up ; treatment failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A considerable fraction of first metastases in breast cancer patients are found in the skeletal system. Consequently, to improve the probability of detecting bone lesions, protocols of the National Surgical Adjuvant Breast and Bowel Project (NSABP) have required radionuclide scans every six months for the first three postoperative years and yearly thereafter. The present study was conducted to evaluate the worth of 7984 bone scans performed prior to documentation of first treatment failure on 2 697 stage II (positive node) patients entered into NSABP clinical trial B-09. At the time of evaluation, there were 779 patients with a treatment failure, 163 (20.9%) of whom had their recurrence limited to bone. At most, 52 (0.6%) of the total number of screening scans were efficacious in detecting lesions in asymptomatic patients. As a result of this minimal benefit from routine scans, it was recommended that they be conducted less frequently. In presently ongoing NSABP studies, asymptomatic patients having tumors with positive axillary nodes receive scans at yearly intervals for the first three years. Future NSABP trials will require follow-up bone scans only as indicated by symptoms.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7217
    Keywords: breast cancer ; estrogen receptor ; expression ; immunophilins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The estrogen receptor α (ERα) is implicated in the development of breast cancer. The immunophilins, cyclophilin 40 (CyP40) and FKBP52, are associated with ERα and other steroid receptors in mutually exclusive heterocomplexes and may differentially modulate receptor activity. Since previous studies have not assessed the levels of these immunophilins in breast cancer, we examined 10 breast cancer cell lines for mRNA and protein expression of CyP40 and FKBP52 and for amplification of the CyP40 gene. In addition, 26 breast carcinomas, including seven with matched normal breast tissue, were examined for mRNA expression of both immunophilins. CyP40 and FKBP52 were ubiquitously expressed in breast cancer cell lines, but there were significant differences in their pattern of expression. FKBP52 protein levels were generally an order of magnitude greater than those for CyP40. FKBP52 mRNA expression correlated strongly with protein expression and was significantly higher in ERα-positive compared with ERα-negative cell lines. However, CyP40 mRNA expression did not correlate with protein expression, nor did expression of this immunophilin correlate with ERα status. Relatively high expression of CyP40 in one cell line (BT-20) could be attributed to amplification of the CyP40 gene. Both immunophilins were also ubiquitously expressed in breast carcinomas, and we demonstrate for the first time that both CyP40 and FKBP52 mRNA are overexpressed in breast tumors compared to matched normal breast controls. The overexpression of CyP40 and FKBP52, coupled with relative differences in their expression in tumors, may have important functional implications for ERα and other steroid receptors in breast cancer.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-7217
    Keywords: active processed cathepsin D ; breast cancer ; prognostic indicator ; survival analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The relative amounts of the precursor (52 kDa) and processed (31,27 kDa) forms of cathepsin D have been analyzed by Western blotting in biopsied breast tissue cytosols from 134 lesions from invasive breast cancer patients, 24 lesions from patients with ductal carcinoma in situ (DCIS), 227 lesions from benign breast disease patients, and 28 lesions from normal control subjects. The mean relative percentage amount of the 31 kDa form was significantly increased (p〈0.001) in the invasive breast cancer group compared to the other three groups. In addition, the mean relative percentage amount of the 31 kDa form was significantly increased (p〈0.05) in node-positive compared to node-negative breast cancer patients. In the benign breast disease group, patients with proliferative-type disease had a significantly increased (p=0.02) mean relative percentage amount of the 31 kDa form of cathepsin D compared to patients with nonproliferative-type disease. Invasive breast cancer patients were followed for up to 75 months to determine if the relative percentage amount of the 31 kDa form of cathepsin D was predictive of disease-free and overall survival. Although the amount of the 31 kDa form was not predictive of disease-free survival, patients in the ‘high’ 31 kDa group (〉18) were significantly (p〈0.05) more likely to die than patients in the ‘low’ 31 kDa group (≤18%). The 12 patients who died were all node-positive and in the high 31 kDa group. It thus appears that the relative amount of the processed, active 31 kDa form of cathepsin D is a useful prognostic indicator, at least in node-positive breast cancer patients.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 215 (1981), S. 499-504 
    ISSN: 1432-0878
    Keywords: Androgen receptors ; Pituitary gland ; Rhesus monkey ; Autoradiography ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The uptake and retention of radiolabelled dihydrotestosterone by the pituitary gland was examined in the rhesus monkey. Two animals were given an intravenous injection of 1.0μg/kg 3H-dihydrotestosterone (DHT) alone while one monkey received both the labelled androgen and 100μg/kg of unlabelled steroid. One and a half hours later, they were sacrificed. The pituitary glands were removed and processed for autoradiography and immunocytochemistry. Autoradiographic localization of DHT was discernible in the partes nervosa, intermedia and distalis, albeit the highest concentration of radiolabelled cells was noted in the pars distalis. Immunocytochemical staining with antibodies to rat PRL, human TSHβ and ovine LHβ revealed a population of steroid-concentrating cells that contained TSH and a second group that contained LH. None of the cells that reacted with the anti-PRL serum were radiolabelled.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 231 (1983), S. 593-601 
    ISSN: 1432-0878
    Keywords: Lymphatic organs ; Sex steroids ; Baboon ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The localization of radiolabeled estradiol and dihydrotestosterone was examined in the lymphatic organs of both male and female baboons. A total of 12 baboons were divided into two groups, each containing three males and three females. Each animal in one group, both males and females, was injected intravenously with 1 μg/kg body weight of 3H-estradiol while those in the second group were each injected with 1 μg/kg body weight of 3H-dihydrotestosterone. As controls, one male and one female from each group also received a dose of 100 μg/kg body weight of the corresponding unlabeled steroid. One and a half hours after the injections, the animals were sacrificed and the spleen, thymus, and inguinal lymph nodes removed and processed for autoradiography. The localization of 3H-estradiol was similar in both males and females. In the thymus fibroblasts and epithelio-reticular cells, but not thymocytes, localized 3H-estradiol. In lymph node and spleen, nonlymphoid tissue concentrated the labeled estrogen. Additionally, in the paracortical region of the lymph node, an unknown cell type was labeled with estrogen. Only one male baboon demonstrated nuclear localization of 3H-dihydrotestosterone. This was observed in the reticular cells in the spleen and lymph nodes. The same cell type in the organs of the remaining animals was unlabeled.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 183 (1977), S. 379-384 
    ISSN: 1432-0878
    Keywords: Brain ; Rat ; Diethylstilboestrol ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The cellular and subcellular localization of radioactivity in the brain of immature female rats was determined by dry-mount autoradiography 2 h after iv injection of 1.0 μg of (monethyl-3H) diethylstilboestrol per 100 g body weight. A specific topographic pattern of nuclear concentration of the synthetic oestrogen was obtained similar to that for 3H-oestradiol-17β in specific neurons of the basal hypothalamus, preoptic region and amygdala. In competition experiments, the nuclear concentration of radioactivity in all areas studied was inhibited by unlabeled oestradiol, while unlabeled testosterone had no effect. These data suggest that although oestradiol can bind to androgen receptors, the oestrogen receptor itself can account for the localization seen after the injection of 3H-oestradiol.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 230 (1983), S. 219-223 
    ISSN: 1432-0878
    Keywords: Steroid receptors ; Estradiol ; Diabetes mellitus ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Previous clinical studies have indicated that during pregnancy and following administration of contraceptives women show altered carbohydrate metabolism. We performed autoradiographic studies using 3H-estradiol-17β and 3H-dihydrotestosterone on male and female baboons. Discrete sites of localization of exposed photographic emulsion were observed over nuclei of cells of the islets of Langerhans of the pancreases of baboons injected with estrogen but not over those of baboons injected with androgen. These observations that islet cells contain specific receptors for estrogen when combined with the clinical observations, suggest that estrogens have a direct effect on the islet cells that may modulate the release of insulin.
    Type of Medium: Electronic Resource
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