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)

We have demonstrated that natural beta-interferon (beta-IFN) enhances estrogen receptor (ER) mRNA of a human breast cancer cell line, CG-5. Cells were sensitive to the effect of beta-IFN at concentrations ranging from 10 to 100 IU/ml. The increase of ER mRNA was seen after 48 hr of treatment in at least three separate experiments. Our results are in agreement with the previously observed enhancement of receptor protein. In addition, they suggest that the IFN-induced promotion of the antiproliferative activity of drugs which act via ER may be due, in part, to increased receptor synthesis.
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PMID:Effect of natural beta-interferon on estrogen receptor mRNA of breast cancer cells. 129 49

The over-expression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian, endometrial and mammary carcinoma is an important indicator for poor prognosis. We have previously shown in 3 out of 4 ovarian carcinoma cell lines an interferon-gamma (IFN-gamma)-mediated reduction in HER-2 specific protein and RNA levels. The oncogene expression was lowered only in the ovarian carcinoma cell lines but not in 3 IFN-gamma-sensitive human breast cancer cell lines. We extended our observations also to IFN type I, alpha and omega. The expression of the oncogene was measured by both the p185HER-2 ELISA and in selected cases by a living cell radioimmunoassay using the monoclonal antibody (MAb) 4D5 against the extracellular domain. Both IFN types reduced the expression of HER-2 in the ovarian carcinoma cell lines OVCAR-3, HTB-77, 2774 and SKOV-6, and in the SKUT-2 endometrial carcinoma cells. In contrast, SKOV-8 human ovarian carcinoma cells were sensitive for both IFN types regarding proliferation, but only IFN-gamma reduced proto-oncogene expression. In the SKBR-3 human mammary carcinoma cells, neither IFN type had an effect on HER-2 expression. The antibodies 4D5, 7C2, 3E8, and 3H4 which bind to the extracellular domain of p185HER-2 protein specifically inhibited anchorage-independent growth of SKBR-3 and HTB-77 cells. Expression of the oncogene HER-2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which IFNs inhibit cell proliferation.
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PMID:Effects of interferons on the expression of the proto-oncogene HER-2 in human ovarian carcinoma cells. 137 Feb 27

For resistant local recurrence, e.g. in breast cancer, or metastatic spread, local infiltration of IFN may be an interesting new approach. The aim of this study was to find out if intrapleurally administered interferon, in breast cancer patients with pleural carcinomatosis, can cause measurable serum concentrations and how soon after administration. Serum IFN concentrations were compared with those in the pleural fluid, and correlated with the presence of malignant cells in the pleural fluid. To uncover possible rhythmicity of serum interferon levels and its relationship to the timing of therapy, natural leukocyte interferon was administered intrapleurally at 10 a.m. Data on pharmacokinetics were obtained from blood samples drawn at -2, 0, 2, 8, 14, 22 and 46 h during the course of treatment. In contrast to our previous observations in healthy volunteers, levels of serum IFN before therapy had no circadian rhythmicity. Daily pharmacokinetic profile of individual patients on interferon therapy has shown that serum IFN peaks 8 h after intrapleurally administered IFN alpha. The peak depended on frequency and number of applied doses. During treatment with IFN alpha, malignant cells degenerated and finally disappeared from pleural fluid. At the same time reactive cells appeared. This effect is rather uniformly observed, but varies in degree. The number of patients is too small, however, to permit conclusions in regard to correlation of this clinical effect and the levels of serum IFN alpha.
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PMID:Intrapleural application of natural IFN alpha in breast cancer patients with pleural carcinomatosis. Monitoring of immunotherapy by assaying serum interferon levels. 141 64

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

To date, the results concerning the prognostic importance of parameters of cell-mediated immunity in breast cancer patients are very contradictory; moreover, in most of them the results are hardly comparable due to methodological differences and heterogeneous groups of patients. In 123 patients with nonmetastatic breast carcinoma TNF alpha, INF alpha, IL 2 and reactivity in the leucocyte migration inhibition test (LMI-Test) against autologous tumor tissue were determined and the results correlated with the clinical course of the disease up to a maximum of 108 months. In breast cancer patients TNF alpha-serum levels were significantly (p less than 0.05) elevated compared to healthy controls. We also found that patients with progressive disease had higher levels than patients without recurrences. There were no differences concerning the IL-2 and IFN alpha serum levels between cancer patients and controls, nor did we find a correlation with the clinical course of the disease. In 38% of all breast cancer patients examined, a MIF production against tumor tissue could be demonstrated in the LMI-test. There was no difference concerning the LMI-reactivity between the groups of lymph-node negative and positive patients, but the observation that those patients with an unfavourable clinical course respond more frequently with an enhanced macrophage migration and rarely with migration inhibition was considered of notable prognostic significance. According to these results, it is possible that determination of TNF alpha and delayed type hypersensitivity reaction against tumor tissue in the LMI-test is of clinical value for the determination of risk groups.
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PMID:Determination of TNF alpha, interferon alpha, interleukin 2 and reactivity in the leucocyte migration inhibition test in breast cancer patients. 174 7

The effects of recombinant gamma interferon (IFN gamma) on proliferation, estrogen-receptor (ER) content, mRNA level and protein secretion of a breast cancer estrogen-induced protein pS2/BCEI were investigated in two human breast cancer cell lines, ZR75-1 and T47D. Both cell lines have estrogen and progesterone receptors and previously showed HLA class I and class II responses to IFN gamma (Int J Cancer 1990; 45: 1169). An antiproliferative effect of IFN gamma (1000-5000 U/ml) was observed in serum containing medium on ZR75-1 but not on T47D cells. Noninhibitory concentration of IFN gamma (100 U/ml) had sensitising antiproliferative effect with antiestrogens on ZR75-1 cells whereas IFN gamma did not modify the growth inhibition observed in T47D cells with antiestrogens. In serum-free, estradiol-free, phenol-red-free chemically defined medium (Cancer Res 1984; 44: 4553), IFN gamma abolished in ZR75-1 but not in T47D the 30% growth stimulation induced by estradiol. In ZR75-1 cells, IFN gamma induced a transitory 30-50% increase of ER content, as measured by ER-enzymoimmunoassay, at day 2 of culture, and reduced mRNA level and secretion of pS2/BCEI. In T47D cells, a 30-50% decrease of ER content was observed but only when cells were long term cultured (30 weeks) with IFN gamma. In this cell line, no transcription of pS2/BCEI was observed. Antiproliferative action of IFN gamma on ZR75-1 cells is associated with an inhibition of estradiol effects and a reduction of pS2/BCEI mRNA level and protein secretion.
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PMID:Modulation of proliferation, estradiol receptors and estrogen regulated protein PS2/BCEI in human breast cancer cell lines by gamma interferon. 176 58

We have studied the mechanism of the synergistic effect of the combination of tumor necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha) on cell cycle progression using two-parameter flow cytometry in vitro and an immunohistochemical staining method in vivo. The cells used were human colon cancer cell line RPMI 4788 in vitro and in vivo, and human breast cancer cell line MX-1 and human renal cancer cell line NAMKO-1 in vivo. In the in vitro experiment, the cell cycle progressed normally as time elapsed in the control group. However, in the group treated with TNF-alpha and IFN-alpha in combination (combination group), it appeared that the transition from the S phase to the G2/M phase was blocked, and the cells that accumulated in the S phase died. In the in vivo experiment with male nude mice of a CD-1 genetic background, the antitumor effect on all three kinds of cancer cells was significantly greater in the combination group than in the control group. The cell labeling index on staining with bromodeoxyuridine in the combination group became markedly larger and the mitotic index smaller than in the other groups. From these results, it was concluded that in the combination group, both in vitro and in vivo, tumor cells markedly accumulated in the S phase and their progression from the S phase to the G2/M phase in the cell cycle was inhibited.
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PMID:Mechanism of the combined antitumor effect of natural human tumor necrosis factor-alpha and natural human interferon-alpha on cell cycle progression. 182 50

Aggressive polychemotherapy and ultraradical surgery had had only small benefits for patients with gynaecological cancer in recent years. That is why we measured cytokines in these patients to evaluate a possible future immune therapy. To investigate the influence of gynaecological cancer on in vitro and in vivo cytokine production of peripheral mononuclear cells (PBMC) from 27 patients with mamma carcinoma and 29 patients with cervical cancer, we evaluated the production of interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). We compared the immune function of these patients versus 20 patients who had had routine hysterectomies performed for non-malignant reasons and 20 healthy female controls. Blood for cytokine production was collected prior to surgery, for IFN-alpha-production two weeks after surgery and for all cytokines three months after surgery. Measurement of TNF-alpha-production did not differ significantly in all investigated groups. IFN-gamma-production was reduced by 50% in patients with mamma carcinoma in three months - possibly caused by chemotherapy and radiation. The amount of IFN-alpha production in cancer patients was dramatically reduced before primary therapy started. The low levels of IFN-alpha persisted for three months compared to the IFN-alpha production in non-cancer patients and healthy controls. The follow-up of patients with breast cancer undergoing chemotherapy showed a suppressive effect on immunological function in IFN-alpha. Our results demonstrate, that patients with breast cancer and cervical cancer showed a significantly reduced capacity to product IFN-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cytokine production by gynecologic cancers]. 190 47

The values of parameters of humoral immunity, such as concentration of immunoglobulins IgG, IgA, and IgM, as well as the absorbance of patients serum at 450 nm (A4 5 0) in the presence of PEG 6000 (as a measure of the presence of immune complex in circulation, CIC) in a group of breast cancer patients stage T + N0 M0, after surgical tumor resection, and before and after various therapy phases with the leucocyte IFN therapy are given. The IFN (product of Torlak, Belgrade, or Immunological Department Zagreb) therapy was performed in four therapy phases. During the first month (first phase) 3.10(6) U IFN-alpha were administered i.m. every day, during the second month 3.10(6) U were administrated thrice weekly, during the third month 3.10(6) U IFN-alpha were administered i.m.twice weekly, and during the fourth month 3.10(6) U IFN were administered i.m. once a week. The average concentration of IgG, IgA, and IgM fall in the range of normal values during the therapy. Nevertheless, some mild stimulation of the IgG production and transient one for IgA can be noticed. The average value of A4 5 0 for patients was before therapy significantly (P less than 0.05) higher than normal value--at the end of the therapy it was in the range of normal A4 5 0.
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PMID:[Parameters of humoral immunity in patients with breast carcinoma during therapy with leukocyte interferon]. 191 52


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