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

Five tumor markers were measured simultaneously in serum by radioimmunoassay: carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), human chorionic gonadotrophin (HGC), the beta subunit of HCG, and Kappa casein. In a population of 935 normal subjects these antigens were undetectable or found within precise limits. In patients with tumors of various origins the rate of pathologically elevated levels was 72% at the beginning of the clinical course (194 cases). This high rate was primarily due to the simultaneous measurement of CEA, betaHCG, HCG, and casein. AFP was of little importance. The simultaneous measurement of these tumor markers may be one biochemical element of diagnosis of carcinoma, although this criterion is neither absolute nor specific, as 14.7% of patients with non-neoplastic disorders (234 cases) were positive for one antigen. In the presence of metastases (112 cases) the rate of pathologic levels of at least one antigen was increased: 86% due to CEA and casein assay at the same time as their absolute levels were increased. Surgical removal reduces the rate of positivity of these antigens to 37%. As was shown in patients with breast cancer, the rate was 10% when the tumor had been removed at Stage N- and 54% when it was removed at Stage N+. Thus, the persistence of pathologic levels could be correlated with the capacity for recurrence or metastases. Finally chemotherapy, radiotherapy, or both, do not decrease the rate of positivity of the tumor markers.
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PMID:Simultaneous assays of cancer-associated antigens in various neoplastic disorders. 6 15

A retrospective study of ninety-six cases of breast cancer was carried out to determine the prognostic values of a casein immunolocalization technique. This was performed using an indirect immunofluorescence method with antisera raised in rabbits to pooled human casein. Fluorescence positivity was graded according to its intensity and distribution. The pathology of each tumour was studied and the tumour type, histological grade and tissue response assessed. The relationship between these observations and the casein content of the tumour was studied. In addition the correlation between casein content and age, menopausal state, clinical staging and survival was investigated. The incidence of casein positivity in our series was 50% with approximately half of the positive cases showing strong fluorescence. There was a relationship between casein content and the age of the patients, with casein being more frequently found in tumours from younger patients. Tumours with a high casein content, in general, show a poorer survival than the group as a whole. This difference in survival was most marked in the first eight years after operation and restricted to those tumours in clinical stage I and histological grade I. The presence of casein in the tumours did not appear to be related to the other factors examined.
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PMID:The identification of 'casein' in human breast cancer. 38 73

Currently, one could summarize this area by saying that we appear to be in a situation where three relatively nonspecific tests detect the majority of patients with metastatic disease, as well as those post-operative patients who are at high risk of relapse. The critical test of their utility for segregating those at risk for relapse from those who are not at high risk will need to be done in a highly select subgroup, e.g., N- patients. Two of these tests, CEA and hCG, also appear to be useful indicators for predicting the probability of responding to combination chemotherapy in metastatic disease. The development and further testing of potentially more specific markers to replace or add to the current matrix is now in progress, Casein, which is a product of the milk synthesis pathway of breast tissue, represents a potentially more specific test than any of those studied to date. HENDRICK and FRANCHIMONT, 1974, have found elevated levels in 21 of 26, or 81%, of patients with metastatic disease, and 8 of 11, or 73%, of patients preoperatively. The test may also reflect the tumor burden since the proportion of patients with elevated levels dropped to 41-50% postoperatively. Further results with this marker are awaited with interest. Other tests such as ferritin, hydroxyproline, or the development of tumor antigen associated immunospecific assays could increase both the specificity and sensitivity of the tests utilized in this field of investigation. Injecting the use of both single marker tests and matrix approaches into routine clinical use in the postoperative setting now appears to be ready for more critical testing. Their use in diagnostic or screening settings, which is the ultimate goal, also needs to be evaluated. Finally, from the practising clinician's viewpoint the data in this discussion should be considered preliminary. It constitutes a status report. Although there is evidence that CEA and hCG are prognostic in metastatic disease, and that subclinical disease is detectable, larger and more tightly controlled studies will be necessary before their routine clinical use can be recommended in breast cancer patients.
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PMID:Biochemical markers in cancer of the breast. 79 22

Casein was measured in the sera of breast cancer patients, in breast cancer tumors, and in breast cancer cells in long-term tissue culture using a sensitive and specific radioimmunoassay. Levels present in breast cancer sera were not elevated above control values. Eight of forty-seven (17%) of the tumor samples tested were positive for casein, the highest level representing 0.003% of the soluble protein. When seven human breast cancer cell lines were assayed for casein, the results were uniformly negative even under conditions of stimulation by lactogenic hormones. In addition, direct immunoprecipitation of labeled cellular protein supported the negative result of the radioimmunoassay. Thus it appears that casein production is not a common characteristic of most human breast cancers.
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PMID:Casein production by human breast cancer. 83 74

Temperature in man measured or recorded by different means, is not constant but varies in a predictable and rhythmic fashion. Circadian (about 24-hour) rhythms have been demonstrated and studied in healthy men and women as well as in patients under a wide variety of experimental conditions and diseases. With the help of special computer programs (Halberg's cosinor) inferential statistical analyses can be performed. There validate and characterize a biological rhythm (i.e., core temperature) by several parameters: the period (tau) the acrophase (phi) (timing of the peak), the amplitude (A) and the rhythm-adjusted mean (M). Each one of these parameters is given with its confidence limits when the studied rhythm is detectable (p less than 0.05). The human temperature (oral, rectal and skin) circadian rhythm has been validated and quantified in healthy newborns, in healthy adults on various diets (including near-fasting conditions: 220 cal/24h, casein) and various type of activities. Food intake does not appear to influence the temperature circadian rhythm. The rhythm persists with a change of period and/or acrophase during isolation underground, without time dues or clues. Its acrophase can be shifted by manipulating synchronizing factors (i.e., shift-working, transmeridian flight). Alteration of circadian temperature rhythm may result from the timed administration of certain drugs (i.e. reserpine) and from certain chronic diseases (without overt fever). A first attempt to use both thermography and chronobiological method has been made independantly by Gautherie et al [40] and Smolensky [41] in the prediction of therapeutic value of a given modality during the course of breast cancer treatment.
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PMID:Circadian changes in the temperature of human beings. 110 84

beta-Casein genes expression in breast epithelium was studied in male patients with various forms of gynecomastia and cancer. Blood serum levels of pituitary, sex and glucocorticoid hormones were assayed in 29 patients with gynecomastia and 22 cases of breast cancer, and in 25 of them beta-casein genes expression was evaluated additionally. Activation of the above genes was established in the tissues studied. Their level proved to be in a correlation with that of prolactin.
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PMID:[The determination of beta-casein gene expression and the assessment of hormonal homeostasis in gynecomastia patients and in breast cancer in men]. 130 Jul 68

A panel of nine monoclonal and polyclonal antibodies were tested regarding specificity for metastatic breast cancer. A hundred metastatic tumors were stained, 50 of breast origin and 50 of other origins. Antibodies used were anti-alpha-lactalbumin, anti-lactoferrin, anti-casein, E29 (Dako-EMA), anti-secretory component, anti-gross cystic disease fluid protein (GCDFP15), BRST1, BRST2, and MC5. Analyses of the results were performed using chi-square and logistic regression. Positivity for MC5, BRST1, BRST2, lactoferrin, EMA, and GCDFP15 was significantly higher in tumors of breast origin than in others (p less than 0.05). Analyses of the whole panel indicated that GCDEP15 and MC5 were the best markers for identification of breast cancer metastases. When both were positive (58% of breast origin cases), the predicted probability of breast origin was 98%, compared to only 5% when both were negative. Comparison of anti-GCDFP15 with BRST2, a monoclonal antibody against the same protein, showed a slightly better sensitivity of the former, and a similar degree of specificity for breast tissue. In conclusion, a panel of antibodies can be used to securely differentiate metastatic breast cancer from other cancers in a large number of metastatic tumors of unknown origin.
Breast Cancer Res Treat 1992
PMID:Immunohistochemical markers in the identification of metastatic breast cancer. 132 17

The human erbB-2 oncogene encodes a tyrosine kinase receptor. A ligand for the erbB-2 receptor (gp30), with an apparent molecular weight of 30,000, was reported to modulate the growth of cells overexpressing erbB-2. Whereas low concentrations of gp30 induced proliferation of these cells, higher concentrations inhibited their growth. To elucidate the cellular mechanisms underlying cell growth inhibition by gp30, we tested the effect of this ligand on cell growth and differentiation of the human breast cancer cells AU-565 and MDA-MB-453 (which overexpress erbB-2) and MCF-7 cells (which express low levels of this protooncogene). Ligand concentrations that inhibited growth in cells overexpressing erbB-2 induced apparent differentiation of cells with a more mature phenotype, i.e., with characteristics such as inhibited cell growth, altered cytoplasmic and nuclear morphology, and increased synthesis of milk components (casein and lipids). No significant effect of the ligand was observed in the human breast cancer cell line MCF-7. Concomitant with the induction of differentiation in AU-565 and MDA-MB-453 cells, the erbB-2 protein was translocated from membrane to the cytoplasm and perinuclear sites. These findings indicate that ligand-induced growth inhibition in cells overexpressing erbB-2 is associated with an apparent induction of differentiation.
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PMID:A ligand for the erbB-2 oncogene product (gp30) induces differentiation of human breast cancer cells. 135 80

The HER-2/neu protooncogene (also called erbB-2) encodes a tyrosine kinase receptor for a polypeptide growth-regulatory molecule. Amplification and overexpression of the gene have been frequently observed in human adenocarcinomas and correlated with poor prognosis. To explore the potential of antibody therapy directed at the HER-2/Neu receptor, we have raised a panel of murine monoclonal antibodies to the human protein, and tested their effect on the tumorigenic growth of HER-2/neu-transfected fibroblasts in athymic mice. We previously reported that the i.p. injected antibodies either inhibited or accelerated the tumorigenic growth of HER-2/neu transfectants in athymic mice. Here we report that these opposing effects were induced also by i.v. injected antibodies, they lasted over 7 weeks, and were probably mediated by distinct epitopes on the receptor molecule. To understand the cellular mechanisms underlying antibody-induced tumor inhibition, we tested the effect of the monoclonal antibodies on various cultured human breast cancer cells. Our analysis revealed that the tumor-inhibitory antibodies specifically induced phenotypic cellular differentiation that included growth arrest at late S or early G2 phase of the cell cycle, markedly altered cytoplasm and nuclear morphology, synthesis and secretion of milk components (casein and lipids), and translocation of the HER-2/Neu protein to cytoplasmic and perinuclear sites. The extent of cellular differentiation by various antibodies could be correlated with their tumor-inhibitory potential, whereas a tumor-stimulatory monoclonal antibody or control immunoglobulin were completely inactive with respect to cellular differentiation. Taken together, our in vivo and in vitro studies correlate the tumor inhibitory potential of monoclonal antibodies to HER-2/Neu with their capacity to induce cellular differentiation in vitro. This observation may hold promise for immunotherapy of cancers that express the HER-2/neu oncogene.
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PMID:Tumor-inhibitory monoclonal antibodies to the HER-2/Neu receptor induce differentiation of human breast cancer cells. 137 72

The relationship between terminal cell differentiation and changes in the subcellular levels of the HER-2/neu antigen was investigated in cultured human breast cancer cells: AU-565 cells (which overexpress the HER-2/neu gene) and MCF-7 cells (which do not overexpress this gene). Differentiation was achieved by treating the cells with mycophenolic acid (MPA), phorbol 12-myristate 13-acetate (PMA), retinoic acid (RA), or the TA-1 monoclonal antibody to the extracellular domain of the HER-2/neu protein. Ten to twenty percent of the cells in untreated, sparsely growing AU-565 cultures exhibited morphological maturation characterized by large lacy nuclei surrounded by sizable flat cytoplasms. A fraction of these cells harbored milk factors such as casein and large lipid droplets. Treatment of the AU-565 cells for 4 d with 9 microM MPA, 1.6 nM PMA, 2.5 microM RA, or 1 microgram/mL TA-1 antibody resulted in cell growth inhibition and an increase in the percentage of cells (48-97%) that exhibit a mature phenotype. MCF-7 cells were also susceptible to differentiation by MPA and RA, but to a lesser degree than the AU-565 cells. Differentiation in the AU-565 and MCF-7 cells was associated with reduced immunostaining for the HER-2/neu protein at the cell surface membrane and with a transient increased diffuse immunostaining for this protein in the cytoplasm.
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PMID:Differentiation of cultured human breast cancer cells (AU-565 and MCF-7) associated with loss of cell surface HER-2/neu antigen. 198 May 88


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