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)

Cytokine-induced modulation of HLA expression on the cell surface of four human breast cancer cell lines was determined by continuous flow immunocytofluorometry with the aid of monoclonal antibodies directed to a non-polymorphic determinant of HLA class I and class II (DR) antigen. IFN-gamma and IFN-alpha were potent inducers of HLA class I in all examined cell lines, with decreasing inducibility as follows: BT-20, ZR-75-1, MCF-7 and MDA-MB-468 cells. HLA class II (DR) antigen was highly inducible by IFN-gamma in ZR-75-1 cells, followed by BT-20, MDA-MB-468 and MCF-7 cells. IFN-alpha increased the cell surface expression of DR antigen only in ZR-75-1 cells. IL-1-alpha induced a moderate level of HLA class I antigen in ZR-75-1, BT-20 and MDA-MB-468 cells, and HLA class II (DR) expression only in ZR-75-1 cells. This pattern of cell line inducibility by IL-1-alpha was similar to that induced by TNF-alpha. Differences in inducibility of HLA antigens on human breast cancer cell lines induced by different cytokines may reflect the differences in cytokine inducibility of the original tumor cells.
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PMID:Cytokine (IFN-alpha, IFN-gamma, IL-1-alpha, TNF-alpha)-induced modulation of HLA cell surface expression in human breast cancer cell lines. 143 41

Cytokine gene expression in tumor-infiltrating lymphocytes (TIL) in frozen-tissue sections of 2 types of human solid tumor--ovarian adenocarcinoma and invasive breast cancer--was examined by in situ hybridization with 35S-labeled cDNA probes for human cytokines. The proportion of cells containing mRNA able to hybridize to the antisense c-DNA probes for interleukin 2 (IL-2), tumor necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) or receptors for IL-2 (either p55 or p70) was also determined in human normal peripheral lymphoid tissues and inflammatory tissues. Few cells were positive for IL2 and TNF alpha mRNA in reactive human lymph nodes and tonsils. Inflammatory lesions, such as salpingitis or chronic active hepatitis, contained 10-20 times more cells positive for cytokine mRNA than reactive lymphoid tissue. In contrast, tumor-infiltrating lymphocytes (TIL) in the stroma of ovarian carcinomas or most ductal breast tumors only rarely expressed mRNA for TNF alpha, IL2 or IFN gamma. The intensity of mononuclear cell infiltration in these tumors correlated positively with the percentage of cells which expressed mRNA for IL-2, TNF alpha and IL-2R. In those ductal breast carcinomas which contained intracellular or intraductal mucins, up to 30% of lymphoid cells in the tumor stroma were positive for IL-2, TNF alpha, IFN gamma and IL-2R. Thus, strong evidence for local activation of mononuclear cells in situ, exemplified by the expression of genes for cytokines, was obtained only in inflammatory lesions and in mucin-producing breast carcinomas. In most carcinomas studied, few TIL expressed genes for cytokines as measured by in situ hybridization. Thus, human solid tumors appear to differ in their ability to induce gene expression for cytokines in TIL.
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PMID:Expression of mRNA for cytokines in tumor-infiltrating mononuclear cells in ovarian adenocarcinoma and invasive breast cancer. 160 21

Primary breast cancers from 19 patients and draining lymph nodes from nine of them (seven containing metastatic tumor) were used in growing tumor-infiltrating lymphocytes (TIL) in culture. TIL were studied for proliferation, phenotype, cytotoxicity, and the ability to secrete cytokines in response to autologous tumor. Lymphocytes from primary breast tumors proliferated in 15 of 19 cultures, a median of 6.7 x 10(3)-fold in 65 days. For eight of nine patients, lymphocytes derived from draining lymph nodes proliferated in culture, a median of 110-fold in 49 days. Breast TIL became predominantly CD4+ cells over time in culture and were 73% CD4+ and 21% CD8+ (means) at 63 days (median). Lymph node lymphocytes were 63% CD4+ at 51 days. TIL were poorly lytic in 4-hour 51Cr release assays. Lysis of autologous tumor occurred in only one of 12 breast TIL and one of nine lymph node cultures. This lysis was low (15% at effector:target = 40:1) and was nonspecific (non-major-histocompatibility-complex restricted). Cytokine secretion was tested by co-culturing TIL with autologous or allogeneic tumors for 24 hours. Cytokines were measured in culture supernatants by enzyme-linked immunosorbent assay or radioimmunoassay. TIL from three of 11 patients specifically secreted granulocyte macrophage-colony-stimulating factor, tumor necrosis factor-alpha and interferon-gamma when stimulated by autologous tumor and not by a panel of four to five allogeneic breast cancers. Cytokine secretion has made possible the identification of lymphocytes infiltrating breast cancers with specific immune reactivity. This finding will guide the development of new immunotherapies for patients with breast cancer.
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PMID:Characterization of lymphocytes infiltrating human breast cancer: specific immune reactivity detected by measuring cytokine secretion. 163 79

Interleukin-6 (IL-6) causes an epithelial to fibroblastoid conversion and an increase in the motility of human ductal breast carcinoma cell lines ZR-75-1 and T-47D. Although IL-6 decreases DNA synthetic activity in these cell lines, the IL-6-induced alterations in cell shape and motility occur independently of inhibition of DNA synthesis per se. Whereas tumor necrosis factor alpha (TNF-alpha) inhibits DNA synthesis in T-47D cells, it does not cause an epithelial-fibroblastoid conversion or other major morphological changes and does not increase cell motility; TNF-alpha rapidly lyses a majority of ZR-75-1 cells. Furthermore, the DNA synthesis inhibitors 5-fluoro-2'-deoxyuridine (FUDR) and methotrexate (MTX) also do not cause effects mimicking the action of IL-6 on cell structure and motility. Transforming growth factors alpha and beta 1, acidic and basic fibroblast growth factors, epidermal growth factor, and insulin-like growth factor-1 (TGF-alpha, TGF-beta 1, aFGF, bFGF, EGF, and IGF-1) have little or no effect on breast cancer cell morphology, which serves to exclude the possibility that the IL-6-induced changes are a consequence of induction of these growth factors by IL-6. 12-O-tetradecanoyl phorbol-13-acetate (TPA) but not 8-bromoadenosine 3',5'-cyclic monophosphate (Br-cAMP) induces changes in the morphology and associative behavior of ZR-75-1 cells that are similar but not identical to those caused by IL-6. The TPA-induced alterations are not blocked by anti-IL-6 neutralizing antibodies; staurosporine inhibits the TPA-induced cell alterations but not those induced by IL-6. IL-6 and TPA used together have a phenotypic effect that greatly exceeds that of either agent alone and results in extensive cell scattering in less than 1 day. These findings are consistent with the hypothesis that IL-6 and TPA induce similar morphological changes and cell scattering via independent pathways.
Cytokine 1991 May
PMID:Interleukin-6 and 12-O-tetradecanoyl phorbol-13-acetate act synergistically in inducing cell-cell separation and migration of human breast carcinoma cells. 165 54

Based on the additive or synergistic antiproliferative effect of interferon and tamoxifen on breast cancer cell lines and on preclinical and clinical data on retinoids alone and in combination with antiestrogen or interferon, we designed a pilot phase II study to test the toxicity of simultaneous administration of interferon-beta (IFN-beta), retinoids (R), and tamoxifen (TAM) and the efficacy of this combination as salvage therapy in a group of patients with metastatic breast cancer (MBC). A total of 49 stage IV breast cancer patients, 11 pretreated with hormones, 26 with chemotherapy, and 12 with both, received 30 mg TAM and two dose levels of IFN-beta and retinyl palmitate. Among 49 evaluable patients, 27 achieved a clinical response (55%; 95% CI 41-69%), 10 had stable disease (20%), and in 12 (25%) the disease progressed. Toxicity with both dose levels was moderate and mainly hepatic. Median response duration, not statistically different in estrogen receptor-positive and negative patients, was 31.4 months (range 4.9-67). Median overall survival was 19.2 months (range 2-69). We have shown that long-term administration of TAM, IFN-beta, and retinyl palmitate is feasible with moderate toxicity. We have also demonstrated that this regimen is active in pretreated MBC patients and that responses are not influenced by receptor status.
J Interferon Cytokine Res 1995 Jul
PMID:Interferon-beta, retinoids, and tamoxifen in the treatment of metastatic breast cancer: a phase II study. 755 30

Uncontrolled clinical trials have shown that parenteral administration of GM-CSF reduces the frequency of chemotherapy-induced mucositis. The mechanism of this effect could be related to acceleration of haematopoiesis and/or increase in functional activation of WBC. We conducted a double-blind, placebo-controlled, dose ranging study of GM-CSF (mol-gramostim) mouthwash in patients with breast cancer during the first treatment cycle of a combination chemotherapy regimen which has historically produced dose-limiting (grade > or = 3) mucositis in approximately 39% of patients. Subjects were randomized to receive either placebo mouthwash (0.1 percent albumin) or one of four concentrations of GM-CSF mouthwash (0.01, 0.1, 1.0 or 10 mcg/ml). The primary endpoint was to evaluate the relationship between dose of GM-CSF mouthwash received and probability of grade > or = 3 mucositis using a logistic model. Solutions were administered four times daily starting within 24 hours of chemotherapy initiation and continuing until the end of the cycle (day 21). Mucositis was assessed on days 1-6, 10, 15 and 21. Day 6 plasma samples were assayed for GM-CSF. Forty-five patients were evaluable for response (nine per dosing group). A 42% risk (15/36) of mucositis grade > or = 3 was evident on day 15 in patients receiving GM-CSF compared to 2 of 9 patients on the placebo arm. No evidence of dose response was found by logistic regression. Five patients had a detectable plasma concentration of GM-CSF (56-209 pg/ml). A positive correlation between GM-CSF dose and leukocyte recovery was noted (P = 0.04).
Cytokine 1995 Jul
PMID:Evaluation of GM-CSF mouthwash for prevention of chemotherapy-induced mucositis: a randomized, double-blind, dose-ranging study. 757 86

Studies on circulating human mononuclear cells and rodents have suggested that cytokines such as interleukin-1 (IL-1) and IL-6 may be paracrine mediators of postmenopausal bone loss. However, the assumption that the concentration of these cytokines is increased in the local bone microenvironment of postmenopausal women is still unproved. To address this question, we aspirated bone marrow from the iliac crest of 40 women during surgery for localized breast cancer and analyzed cytokine release in short term cultures. Cytokine levels in the cell supernatants from premenopausal (n = 12) and late postmenopausal (n = 18) subjects were not significantly different. Bone marrow cells from women who had discontinued estrogen replacement within 1 month before aspiration (n = 5) secreted significantly more IL-1 alpha, tumor necrosis factor-alpha, IL-6, prostaglandin E2, and granulocyte-macrophage colony-stimulating factor than bone marrow cells from either premenopausal or late postmenopausal subjects. Increased levels of IL-6, prostaglandin E2, and granulocyte-macrophage colony-stimulating factor were also observed in cultures from women who were within 5 yr of natural menopause (n = 5). Our data show that estrogen withdrawal is associated with an increased potential of human bone marrow cells to release bone-resorbing cytokines and strengthen the hypothesis that these cytokines may play a role in the accelerated bone resorption after menopause.
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PMID:Increased cytokine secretion by human bone marrow cells after menopause or discontinuation of estrogen replacement. 759 50

To investigate the mechanisms of growth inhibition exerted by TNF-alpha on tumor cells in vitro, we analyzed the cytokine effects on growth and cell-cycle parameters of cultured MCF-7 human breast cancer cells. TNF-alpha exerted a dose-dependent inhibition of MCF-7 cell growth, which reached its maximum at 1000 U/ml TNF-alpha concentrations. Flow-cytometric analysis of cell nuclei revealed two main components in TNF-alpha activity: an earlier cytostatic effect (G1/S block), was followed by nuclear shrinkage and cytolysis. The 55-60-kDa TNF-alpha receptor is involved in the growth inhibitory activity of the cytokine, since the H398 anti-55-kDa receptor antibody significantly counteracted the cytostatic and cytotoxic effects of TNF-alpha while an antibody (htr-9) with agonistic activity on the same receptor produced both cytostasis and cytolysis. Culture conditions strongly influenced the MCF-7 cell response to TNF-alpha. Serum deprivation of log-growing (i.e., high S phase percentage) cultures potentiated the cytotoxic effect, while reduction in S phase cell percentage by preculture in serum-free medium resulted in a significant inhibition of TNF-alpha action. Mitogenic hormones, such as insulin and 17 beta-estradiol+insulin, restored the sensitivity of MCF-7 cells precultured in serum-free medium to both the cytostatic and cytolytic effects of TNF-alpha. The synthetic glucocorticoid hormone dexamethasone, at micromolar concentrations, counteracted the TNF-alpha effect on MCF-7 cell growth. Flow-cytometric analysis showed that dexamethasone did not antagonize the cytostatic activity of either TNF-alpha or htr-9 agonistic antibody, but only the subsequent cytolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Lymphokine Cytokine Res 1993 Dec
PMID:Cytostatic and cytotoxic effects of tumor necrosis factor alpha on MCF-7 human breast tumor cells are differently inhibited by glucocorticoid hormones. 812 60

The effect of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and insulin-like growth factor-1 (IGF-1) on the cytostatic activity of tumour necrosis factor-alpha (TNF-alpha) was studied on the breast cancer cell line, T47D. TNF-alpha completely blocked the potent growth-promoting activity of all three factors on T47D cells. EGF, bFGF and IGF-1 partially antagonized the inhibition of cell growth and thymidine incorporation induced by TNF-alpha. These data suggest that the growth of these breast cancer cells is regulated, in part, by the antagonistic interaction between the cytostatic effect of TNF-alpha and the growth-promoting activity of factors such as EGF, IGF-1 and bFGF.
Cytokine 1993 Mar
PMID:Epidermal growth factor, insulin-like growth factor-1 and basic fibroblast growth factor modulate the cytostatic effect of tumour necrosis factor-alpha on the breast cancer cell line, T47D. 833 30

Normal and neoplastic epithelial cells produce growth factors that can affect cells from different lineages. Epithelial ovarian cancers produce M-CSF and IL-6. In the present study, production of these cytokines has been measured in the apparently normal epithelial cells from which epithelial ovarian neoplasms are thought to arise. Epithelial cells from the surface of premenopausal human ovaries were established in short-term cultures. The cells bound anti-cytokeratin antibodies and exhibited characteristic epithelial morphology by light and transmission electron microscopy. M-CSF and IL-6 were detected in supernatants from cultures of these cells, using assays specific for each factor. Cytokine levels were comparable to those in supernatants from ovarian and breast cancer cell lines. M-CSF expression could also be demonstrated by immunohistochemical analysis with specific rabbit heteroantiserum. Thus, M-CSF and IL-6 are produced constitutively by normal as well as by neoplastic ovarian epithelium.
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PMID:Constitutive production of macrophage colony-stimulating factor and interleukin-6 by human ovarian surface epithelial cells. 834 85


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