Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The histologic and immunophenotypic similarities between sweat gland carcinoma and breast cancer are well known. Indeed, these likenesses often preclude the diagnostic separation of primary cutaneous glandular neoplasms from metastatic mammary carcinomas, based on light microscopic and immunohistochemical features alone. To assess whether the presence of estrogen receptor protein (ERP) in breast carcinoma might serve as a diagnostic marker in this context, we analyzed 33 eccrine carcinomas, 24 sebaceous carcinomas, 15 intraepidermal apocrine carcinomas (extramammary Paget's disease), and 42 benign sweat gland tumors for ERP content. The monoclonal anti-ERP H222 was used with a modified avidin-biotin-peroxidase complex (ABC) method and paraffin sections. For comparison, eight cutaneous metastases of mammary carcinomas were similarly studied. ERP was identified in six of eight secondary neoplasms. However, this steroid-binding protein also was detected in 10 of 33 eccrine carcinomas. In three of 10 eccrine hidradenomas, each of two examples of hidradenoma papilliferum, and two of three chondroid syringomas, ERP-reactivity was noted as well. The remaining eccrine, apocrine, and sebaceous neoplasms were nonreactive. Among immunoreactive eccrine neoplasms, eight of 10 carcinomas occurred in males, whereas most ERP-positive benign eccrine tumors arose in females. The potential expression of ERP by sudoriferous malignancies reinforces the biologic similarities between mammary and cutaneous adnexal neoplasms. Moreover, ERP reactivity in the latter lesions underscores the inability of immunohistochemistry to distinguish primary and secondary glandular tumors of the skin with certainty.
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PMID:Immunoreactivity for estrogen receptor protein in sweat gland tumors. 195 42

Studies have suggested that the alpha class glutathione S-transferase (GST) may protect cells from the chemotherapeutic drugs chlorambucil and melphalan. In order to further define the function of human alpha class GST, a complementary DNA which encodes it was ligated into an expression vector under the direction of the human metallothionein-IIA promoter and stably transfected into human MCF-7 breast cancer cells in conjunction with the G418-selectable plasmid pSV2neo. Clonal cell lines were identified which expressed increased levels of GST enzyme activity (2.2- to 5.6-fold). The transfected cell lines also had increased peroxidase activity using cumene hydroperoxide as the substrate (1.9- to 3.8-fold) which is consistent with the intrinsic peroxidase activity of alpha class GSTs. Southern blot analysis indicated that genomic DNA from these cells contained a fragment indistinguishable from the transfected alpha class GST complementary DNA (850 base pairs); Northern blot analysis of total cellular RNA indicated that these cells contained appropriately sized alpha class GST RNA (980 nucleotides); and Western blot analysis indicated that, while MCF-7 cells contained no detectable alpha class GST protein, the transfected cells contained markedly elevated levels of alpha class GST but no detectable mu or pi class GST. These alpha class GST transfected cells had increased resistance to ethacrynic acid (2.1- to 3.0-fold). However, the transfected cells failed to show any increased resistance measured at the drug dosage which inhibited 50% of the colony formation to the chemotherapeutic drugs chlorambucil, melphalan, Adriamycin, or cisplatin under conditions of either continuous or 1-h drug exposure. Neither was there any change in sensitivity to the cytotoxins benzo(a)pyrene, benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (anti), or 1-chloro-2,4-dinitrobenzene. These studies indicate that expression of this human alpha class GST by itself in MCF-7 human breast cancer cells does not confer resistance to the chemotherapeutic drugs tested under the conditions used in these studies.
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PMID:Antineoplastic drug sensitivity of human MCF-7 breast cancer cells stably transfected with a human alpha class glutathione S-transferase gene. 198 77

The effects of GSH depletion in a human breast cancer cell line and a multi-drug resistant subline (ADRr) were determined in a number of experimental conditions. The ADRr cells contained lower GSH concentration which cannot be explained solely on the basis of differences in cell kinetics, and yet the rate-limiting synthetic enzyme gamma-glutamylcysteine synthetase was increased 2-fold. Inhibition of GSH synthesis by BSO resulted in more rapid and more pronounced GSH depletion in ADRr compared to the wild-type cells, suggesting that enhanced GSH utilization and efflux in the resistant cells account for the lowered basal concentration. In addition, the gamma-glutamyl moiety salvage enzyme gamma-glutamyltranspeptidase was reduced markedly in the ADRr cell line. Since these cells have overexpression of the efflux pump protein P-glycoprotein, we examined the effects on cellular GSH of inhibition of the pump's function by verapamil. We found that verapamil significantly depleted cellular GSH. In a rat mammary carcinoma cell line selected in Adriamycin for multi-drug resistance, a similar molecular phenotype has been described including diminished cellular GSH concentration. Verapamil treatment of these cells also resulted in significant depletion of cellular GSH. These results are consistent with the recent report that combined treatment of BSO and verapamil has an additive effect on cytotoxicity. It is likely that decreased basal GSH concentration is due to oxidation and conjugation of it in reactions catalyzed by the enhanced peroxidase and GST found in these cells.
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PMID:Glutathione depletion in human and in rat multi-drug resistant breast cancer cell lines. 199 9

Women with breast cancer have an increased risk of developing primary ovarian tumors. Because a differential diagnosis between primary and metastatic tumors may be difficult in poorly differentiated ovarian neoplasms, breast carcinoma markers may be helpful in establishing the primary site of origin. Gross cystic disease fluid protein-15 (GCDFP-15), a well-known marker of apocrine differentiation, has been reported as a highly specific and sensitive breast carcinoma marker. To evaluate the usefulness of GCDFP-15 as a marker for metastatic breast cancer, we have studied, by the avidin-biotin-peroxidase technique, 14 cases of breast cancer metastatic to the ovary and compared them with 32 primary ovarian tumors and seven cases of ovarian metastases other than breast in origin. Two cases of primary ovarian cancer metastatic to the breast were also included. A strong cytoplasmic immunostaining was found in 10 of 14 cases (71%) of ovarian metastasis from breast carcinoma, and in most cases a characteristic paranuclear staining was noted. All primary ovarian tumors were negative. Ovarian metastases from tumors other than breast and both cases of ovarian carcinoma metastatic to the breast were negative. These results are highly significant (P less than .00001) and demonstrate the value of GCDFP-15 in establishing a primary breast origin among neoplasms of unknown origin involving the ovaries.
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PMID:Value of gross cystic disease fluid protein-15 in distinguishing metastatic breast carcinomas among poorly differentiated neoplasms involving the ovary. 205 Mar 70

A new immunohistochemical assay was developed for the detection of human monoclonal antibody (HuMAb) bound to human biopsied tumor tissues. A murine anti-idiotype monoclonal antibody, alpha type, 18C6 (IgGl), was raised against an IgM HuMAb, L612, defining a tumor-associated ganglioside antigen (GM3) and used as a probe in a three step cell-binding assay (HuMAb + anti-id + biotinylated anti-mouse Ig). Anti-id 18C6 has an exclusive binding specificity for HuMAb L612, but does not interfere with the binding of L612 to antigen positive melanoma cell lines or to a purified antigen, GM3. The applicability of 18C6 in the three step cell-binding assay was tested first using a melanoma cell line, UCLASO-M12. L612 bound to M12 cells was specifically detected by 18C6 without any background reactivity in ELISA. When this assay was compared with the standard two-step cell-binding assay (HuMAb + peroxidase-conjugated anti-human IgM) using various cultured tumor cell lines, parallel reactivity was observed. The three-step cell-binding assay was then applied to various fresh-frozen human tumor sections. Positive reactivity was demonstrated on various histologic types of human tumor tissues: primary melanoma (10/10), metastatic melanoma (4/4), nevus (10/10), lung cancer (3/6), breast cancer (2/6), and colon cancer (1/1). Adjacent normal tissues were unstained. Control experiments included the cell-binding assay with L612 alone, 18C6 alone. L612 + unrelated mouse IgG, and unrelated IgM HuMAb (L72) + 18C6; but biotinylated anti-mouse IgG did not react with these control preparations. The results indicate that anti-id 18C6 is a highly specific probe to assess the expression of the ganglioside antigenic epitope recognized by the L612 HuMAb on biopsied human tumor tissues.
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PMID:Murine monoclonal anti-idiotype antibody (alpha) as a probe to detect human monoclonal antibody bound to human tumor tissues. 223 Jan 46

Two drug-resistant variants of the human breast cancer cell line MCF-7 have been shown previously to exhibit radiation resistance associated with an increase in the size of the shoulder on the radiation survival curve. In the present study, glutathione (GSH) depletion was achieved by exposure of cells to buthionine sulfoximine (BSO) with, in some cases, additional treatment with dimethyl fumarate. Levels of GSH in the adriamycin-resistant subline MCF-7 ADRR are initially lower than in the other two sublines and are depleted to a greater extent by exposure to BSO. Wild-type MCF-7 cells are not sensitized by GSH depletion when irradiated under aerated conditions but are sensitized under hypoxic conditions to an extent which is related to the level of GSH depletion. In contrast both the drug-resistant sublines (MCF-7 ADRR and the melphalan-resistant line MCF-7 MLNR) are radiosensitized by GSH depletion under both aerated and hypoxic conditions. It is hypothesized that in the case of the MCF-7 ADRR cell line, which expresses high levels of the GSH-associated redox enzyme systems, GSH-S-transferase and GSH-peroxidase (GSH-Px), radiosensitization results when GSH-Px is inhibited in GSH-depleted cells. The reasons for radiosensitization of aerated MCF-7 MLNR cells cannot be explained on this basis, however, and other factors are being examined.
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PMID:Radiation response of drug-resistant variants of a human breast cancer cell line: the effect of glutathione depletion. 224 1

With an in vitro culture technique combined with light microscopy, immunocytochemistry and molecular probing, we previously detected occult tumor cells in histologically-normal human bone marrow harvested for autologous transplantation. In this study, we mixed known numbers of malignant lymphoid (Raji and CEM) or breast cancer (MCF-7) cells with normal human bone marrow cells to determine the levels at which tumor cells can be detected before and after culture. Cytocentrifuge preparations were made before culture and after 2 or more weeks of culture and examined by light microscopy. We detected contaminating lymphoma cells at a level of more than 5% before culture, and at a level of 0.01% after culture for 2 or more weeks in 2% human lymphocyte conditioned medium. Before culture, we detected MCF-7 cells at a level of 0.001% using glucose oxidase immunocytochemical staining techniques; these cells were detected at a level of 0.00001% after culture. Since, of necessity, these calibrations rations were performed using cell lines, it is likely that these results overestimate the absolute sensitivity of these methods for detection of tumor cells in patient samples. We found the glucose oxidase immunocytochemical method more specific for detecting occult tumor cells in bone marrow than the immunoperoxidase staining method because of the absence of non-specific staining arising from endogenous peroxidase in bone marrow cells which makes the interpretation of the latter difficult. We conclude that culture techniques can increase the sensitivity of detection of occult tumor cells in human bone marrow about 100-fold.
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PMID:Levels of detection of tumor cells in human bone marrow with or without prior culture. 225 57

The epidermal growth factor receptor (EGF-R) is currently being investigated in human clinical oncology, and particularly in breast cancer, as a potential prognostic factor and a biological target for therapy. As an alternative to the 125I-EGF binding assay, we propose a sensitive immuno-enzymetric assay (IEMA) suitable for EGF-R assay in breast cancer. The assay is performed on solubilized extracts of the 105,000 g pellet of a tumor homogenate, allowing estrogen (ER) and progesterone (PR) assays to be made on the cytosol. The IEMA is performed on 96-well plates coated with the monoclonal anti-EGF-R antibody RI, through an anti-mouse IgG2b bridge. Trapped EGF-R in the samples is covered by a second monoclonal antibody (MAb), 528, and revealed by an anti-IgG2a-peroxidase complex. The sensitivity is 1 fmol/mg membrane protein, and the asay can be performed on tissue samples down to 50 mg. Two hundred and twenty primary ductal breast carcinomas assayed by this method showed a log normal distribution with a modal value of 8 fmol/mg prot., a mean at 18 and a median at 13 fmol/mg prot. EGF-R-rich tumors (greater than 20 fmol/mg prot.) were highly correlated with the absence of estrogen receptors and/or with a high histological grade (SBR III). Our data demonstrate the validity of the IEMA assay of EGF-R in human breast tumors.
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PMID:A simplified immuno-enzymetric assay of the epidermal growth factor receptor in breast tumors: evaluation in 282 cases. 240 3

Anti-estradiol is used as the primary antibody in the peroxidase-anti-peroxidase (PAP) immunoperoxidase (IP) method to visualize putative estrogen-binding sites in potential hormone-dependent tissues and tumours. Basically, 2 different methods are used. The 1st is carried out on fresh-frozen cryostat sections; the 2nd has the advantage to be applicable on current laboratory material, i.e. formalin-fixed and paraffin-embedded material. The various steps of both techniques are analyzed and compared: the potential influence of tissue processing, the necessity of preincubation in estrogens, the physico-chemical conditions of incubation, and the specificity of controls. Van Bogaert (1983) analyzed the drawbacks of the presently available cytochemical techniques used to stain putative estrogen binding sites (EBS) in human breast cancer. In the present paper, a similar investigation is carried out with the aim to evaluate both the technical advantages and possible pitfalls of immunohistochemistry of estrogen receptors (ER) in human mammary carcinoma.
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PMID:Present status of estrogen-receptor immunohistochemistry. 240 27

In men with advanced carcinoma of the prostate who have a breast tumour, it is often difficult to distinguish a primary from a secondary breast lesion. The authors describe the case of a 72-year-old man who presented with a poorly differentiated carcinoma in one breast after receiving estrogen therapy for disseminated prostatic cancer. Application of the unlabelled antibody peroxidase-antiperoxidase immunohistochemical method demonstrated prostate-specific antigen in the tumour cells, thus establishing the secondary origin of the lesion. Five controls--men with primary breast cancer--when tested by the same method did not have this marker. The authors conclude that in this clinical context, prostate-specific antigen is a useful marker of breast cancer in men.
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PMID:Contribution of immunohistochemistry to the diagnosis of breast cancer in men. 242 Apr 31


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