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

The effect of gamma-interferon (IFN-gamma) on the induction of interleukin-2 (IL-2) activated killer cell activity was studied: (I) in peripheral blood lymphocytes (LAK cells) from cancer patients and healthy donors, (II) in lymphocytes infiltrating solid tumors (TIL) from melanoma and breast cancer patients, and (III) in pleural effusion associated lymphocytes (EAL) from patients with lung adenocarcinoma. The coculture of LAK, TIL and pleural effusion mononuclear cells (MNC) with several doses of IFN-gamma (10, 50, 250, and 1250 U/ml) and a low dose of IL-2 (10 U/ml) for 5 days resulted in a synergistic effect on the cytotoxicity of these cells against several tumor cell lines. Furthermore there was a potentiation in the proliferation of MNC after a 5-day culture. The induction of lymphocyte cytotoxicity by a combination of IFN-gamma with low doses of IL-2 may be helpful in designing more effective cancer immunotherapeutic protocols with LAK, TIL or EAL.
 ...
PMID:Gamma-interferon enhances the cytotoxic activity of interleukin-2-induced peripheral blood lymphocyte (LAK) cells, tumor infiltrating lymphocytes (TIL), and effusion associated lymphocytes. 128 41

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.
 ...
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

Interferons (IFNs) have been known to possess an antiproliferative effect on tumor cells besides their well characterized antiviral effect in cell cultures. The mechanism of action of the different IFNs is not fully understood, but in recent years a number of IFN-inducible genes, the presumed mediators of IFN action, have been identified. In the present study we examined the antiproliferative effect of IFN-alpha and IFN-gamma on human breast cancer cells (MCF-7) using (i) the MTT dye formation assay and (ii) anchorage-independent (AI) growth in soft agar. Both IFN-alpha and IFN-gamma were found to have an antiproliferative effect on the growth of MCF-7 cells. In addition, the kinetics of induction of a number of IFN-inducible genes was also examined. The expression of these genes was measured by mRNA analyses using specific [alpha-32P]-labeled cDNAs as probes. The induction of these genes by IFN-alpha and IFN-gamma is a primary effect of IFN, as de novo protein synthesis is not required for their induction. Our results on the kinetics of induction of these genes by IFN-alpha and IFN-gamma suggests a complex mechanism of ligand-dependent gene activation in this cell line with some similar and dissimilar pathways.
Breast Cancer Res Treat 1991 Mar
PMID:Interferon-alpha and gamma mediated gene responses in a human breast carcinoma cell line. 171 85

Pure recombinant human IL-6 inhibits growth of T47D, MCF-7 and SK-BR-3 human breast carcinoma and OVCAR-3 ovarian carcinoma cells in cultures. Subcloning of the breast ductal carcinoma T47D cells yields clones with high and low sensitivity to the growth inhibitory effect of IL-6. The subclones vary 40 fold in their sensitivity for inhibition of colony formation in sparse cultures and 200 fold for inhibition of thymidine incorporation in subconfluent cultures. Binding studies with 125I-rIL6 show that T47D cells and their subclones, as well as SK-BR-3 and MCF-7 cells, express high-affinity receptors for IL-6. The number and affinity constant of these receptors are comparable to those on lymphocytic and myeloid cells, and show no correlation with the high or low sensitivity phenotype. Proliferation of the breast cancer cells is inhibited by IL-6 in a cell density dependent manner, and is not due to a cytotoxic effect. In addition, IL-6 induces a morphological change with loss of epithelial characteristics and of cell-cell adhesion. Sensitivity to growth inhibition by IL-6 is independent from that of IFN-beta 1, IFN-gamma or TNF.
 ...
PMID:IL-6 receptors and sensitivity to growth inhibition by IL-6 in clones of human breast carcinoma cells. 180 60

Tumor-infiltrating lymphocytes (TIL) have been cultured from a variety of human tumors, and some melanoma TIL have demonstrated specific, MHC-restricted recognition of autologous tumor in short term lysis assays. The current study investigates cytokine release by TIL as an indicator of specific tumor recognition. We have identified two of four melanoma and one of seven breast carcinoma TIL cultures that specifically release granulocyte-macrophage-CSF, TNF-alpha, and IFN-gamma after autologous tumor stimulation. The other cultures either do not secrete cytokine or secrete cytokine in a nonspecific fashion. The amount of specific cytokine released is directly related to the number of TIL and stimulating tumor cells. Studies of TIL, from two melanoma patients, separated into CD4+ and CD8+ populations revealed that CD8+ cells were responsible for virtually all of the specific cytokine secretion, although both populations released cytokines when activated by immobilized anti-CD3 antibody. Specific cytokine release by CD8+ TIL was inhibited by anti-MHC class I mAb. Specific cytokine release was also detected from a CD4+ breast cancer TIL culture, and this was inhibited by anti-MHC class II mAb. The clinical significance of this specific mode of immune antitumor reactivity is currently under investigation.
 ...
PMID:Specific release of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and IFN-gamma by human tumor-infiltrating lymphocytes after autologous tumor stimulation. 190 60

Numerous interactions between malignant and stromal/inflammatory cells take place within solid human tumours, which are mediated, in part, by the release of signalling proteins called cytokines. In the present study, we have compared the secretion of two important immunomodulatory cytokines, IFN-gamma and IL-4 by individual, immunophenotyped NK cells freshly isolated from either malignant tumour biopsies, or peripheral blood samples from patients with ductal invasive breast cancer. Due to the marked heterogeneity amongst cells isolated from these clinical samples, we have employed a technique called the reverse haemolytic plaque assay to identify and enumerate cytokine-secreting cells at the single cell level. Our data indicate that NK cells isolated directly from the tumour site secrete more IFN-gamma and IL-4 than NK cells from the blood of the same patients. However, a greater proportion of CD16+ cells from both sources in breast cancer patients secreted IFN-gamma than of those from the blood of healthy donors. We also show that factors secreted by the human breast cell lines, MCF-7 and MDA-231 PN9, were able to mimic the stimulatory influence of the tumour microenvironment on secretory activity of NK cells.
 ...
PMID:Human tumour-associated NK cells secrete increased amounts of interferon-gamma and interleukin-4. 191 Nov 84

Natural and lymphokine activated killer cells (NK and LAK) are believed to play an important role in the control of tumour progression and metastasis. Their specific receptors on tumours cells are still unknown. Several studies suggest that these cells recognise and eliminate abnormal cells with deleted or reduced expression of MHC class I molecules. Previous reports suggest that interferons (IFN), by increasing MHC class I expression on target cells, induce resistance to killing by NK cells. We investigated the role of MHC molecule expression by two human breast cancer cell lines T47D and ZR75-1 in their susceptibility to NK and LAK cells. These two cell lines spontaneously express low levels of HLA class I antigens but no HLA class II molecules. After IFN-gamma treatment they both overexpressed MHC class I and de novo expressed class II molecules as detected by flow cytometry, quantified by a radioimmunoassay and analysed by two-dimensional gel electrophoresis. Opposed to untreated cells these IFN-gamma treated cells were resistant to NK and LAK lysis. Furthermore, preincubation of IFN-gamma treated breast cancer cells with F(ab')2 fragments of monoclonal antibodies to HLA class I and HLA class II molecules was unable to restore lysis. In contrast, several complete monoclonal antibodies including anti-HLA class I and HLA class II induced the lysis of target cells whether or not they had been treated by IFN-gamma. The therapeutic use of monoclonal antibodies directed against antigens expressed on tumour cells (ADCC) in conjunction with interferon therapy should be discussed in lymphokine-based strategies for treatment of cancer patients.
 ...
PMID:Recombinant gamma interferon provokes resistance of human breast cancer cells to spontaneous and IL-2 activated non-MHC restricted cytotoxicity. 210 97

The spontaneous expression of HLA class-I and class-II molecules in 5 human breast carcinoma cell lines, MCF-7, T47D, ZR75-1, HSL-53, MDA-MB 231, and their modulation during IFN-gamma treatment, are reported. The expression of cell-surface determinants was examined by indirect immunofluorescence using monoclonal antibodies (MAbs) specific for HLA class-I and class-II (DR, DQ and DP) antigens. The biosynthesis and maturation of these molecules were analyzed by 2-dimensional gel electrophoresis analysis (2D-PAGE) of class I, DR alpha, beta and invariant immunoprecipitates. Transcription was analyzed by Northern blot hybridization with HLA class-I and -II cDNA-specific probes. In all cell lines, more than 80% of cells expressed HLA class-I antigens at their surface. 2D-PAGE and mRNA studies showed a variable basal level of HLA class-I biosynthesis and transcription with a constant increase after 1,000 U/ml IFN-gamma treatment. HLA class-II determinants were totally absent from the surface of MCF-7, MDA MB231, ZR75-1 and T47D but they were detected in a small subpopulation of HSL-53 cells (DR 6%, DQ 6%, DP 20%). Spontaneous biosynthesis of HLA-DR molecules in immunoprecipitates analyzed by 2D-PAGE or transcripts in Northern blot were not detected in the 5 cell lines. Treatment with 1000 U/ml IFN-gamma induced or increased the expression of HLA class-II molecules in all cell lines but DQ expression was variable. While T47D, ZR75-1 and HSL-53 increased their transcripts and antigen expression, MDA, MB231 and MCF-7 showed no DQ mRNA transcript. Biochemical analysis of the DR products revealed a classical alpha, beta and invariant (li) chain pattern, but indicated a constant glycosylation defect in the invariant chain in all cell lines, associated with weak expression of the beta chain and the presence of an extra spot of low molecular weight in the acidic part of the gel. Thus, post-transcriptional events did not appear to be totally controlled by IFN-gamma in the different cell lines. These differences in DQ expression and glycosylation process in different breast cancer cells may be important in the activation of the immune response among different individuals.
 ...
PMID:Effect of gamma interferon on HLA class-I and -II transcription and protein expression in human breast adenocarcinoma cell lines. 211 15

We have used the nitrosomethylurea-induced rat mammary tumour model to study the effects of parenteral administration of human recombinant tumour necrosis factor (rHu-TNF) and rat gamma interferon (IFN-gamma). An inbred strain of tumour bearing female Ludwig/Wistar/Olac rats were randomised to either treatment or control groups. Two independent studies showed that combined treatment with rHu-TNF and rat IFN-gamma induced significant tumour regression over 4 weeks (P = 0.004, P = 0.005 respectively). Treatment with either rHu-TNF or rat IFN-gamma given individually did not affect the overall rate of tumour growth (P = 0.157 and 0.40 respectively) although an initial reduction in tumour size was observed during the first few days after injection. Measurement of circulating oestradiol levels in groups in which maximum tumour regression was observed showed no statistically significant difference when compared to the control group. Similarly, measurement of oestrogen receptor content showed no statistically significant difference between rHu-TNF-gamma or rat-IFN-gamma treatment or combined treatment of rHu-TNF and IFN-gamma with the control group. We conclude from these observations that combined therapy with rHu-TNF and rat IFN-gamma may prove to be useful new forms of treatment for human breast cancer.
 ...
PMID:Effect of human recombinant tumour necrosis factor and rat gamma interferon on nitrosomethylurea-induced mammary tumours. 249 16

Six different pure human interferons (IFNs), were tested for anti-tumour effect against two human carcinomas, breast and bowel, growing in nude mice, in a total of 36 experiments. The IFN-alpha mixture, analogue and subtypes showed the greatest activity, particularly against the breast cancer xenograft, whereas IFN-beta and IFN-gamma had little effect. However, circulating IFN could be found in the sera of mice treated with all 3 IFN types. In terms of amount of IFN protein, IFN-alpha Con1, an IFN-alpha analogue, was the most effective, a dose of 0.1 micrograms/mouse/day being sufficient to induce breast tumour regression, and IFN-gamma the least effective, a dose of 10 micrograms/mouse/day having no effect on the same tumour. A more detailed comparison of 2 IFN-alpha subtypes showed that a daily dose of 1 microgram IFN-alpha A was more effective than the same dose of IFN-alpha D, but as this IFN had approximately 30 times less antiviral activity on human cells than IFN-alpha D, these IFNs were probably at least equally effective in terms of human cell units. IFN-alpha D stimulated mouse spleen natural killer cell activity but it was not clear whether this stimulation was involved in anti-tumour activity. We conclude that this model system is useful for investigating direct anti-tumour activity of a wide range of IFN types and subtypes.
 ...
PMID:Differential action of six human interferons against two human carcinomas growing in nude mice. 258 1


1 2 3 4 5 6 7 8 9 10 Next >>