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)

Interleukin-6 (IL-6) release from purified blood monocytes was determined in patients with breast cancer or prostatic cancer before and after radiation treatment (Rx). Plasma levels of IL-6 and neopterin were also determined. Spontaneous IL-6 release in vitro was higher in breast than in prostatic cancer or in controls. Strong lipopolysaccharide (LPS)-induced cellular IL-6 release was detected in breast cancer and controls but was subnormal in prostatic cancer. Addition of indomethacin to cultures had no effect on IL-6 release. Rx generally increased levels of in vitro released IL-6 and raised LPS-stimulated IL-6 secretion in prostatic cancer to normal. Plasma levels of IL-6 were lower in breast than in prostatic cancer or controls. Rx resulted in a tendency towards raised levels in both patient groups suggestive of monocyte activation. In accordance with this, plasma levels of neopterin, which were normal before treatment, increased in prostatic cancer patients after Rx. Taken together, the results of this study indicate that monocyte release as well as plasma levels of IL-6 are affected by the malignant state as well as by radiation treatment. In view of the antiproliferative effects of IL-6, the findings may have bearing on the pathogenesis and treatment of malignant disease.
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PMID:Monocyte release and plasma levels of interleukin-6 in patients irradiated for cancer. 145 47

Macrophages from patients with breast cancer showed an impairment of their antiviral activity. The capability to hinder herpes simplex virus type 2 replication of macrophages from healthy donors and from patients with breast cancer was compared to the in-vitro treatment with Escherichia coli lipopolysaccharide (LPS). The LPS showed a dose-dependent effect on the different macrophage populations studied. Nevertheless, macrophages from healthy donors appeared to be more sensitive to LPS in comparison with macrophages from the patients under our observation. On these cells LPS treatment was not able to modify the antiviral property, when these macrophages were differentiated in autologous serum.
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PMID:Modulation of the intrinsic antiviral activity by Escherichia coli endotoxin in macrophages from patients with neoplasia. 185 Apr 54

Bone metastases in breast cancer may be osteolytic, osteosclerotic, or a mixture of the two. Although stimulation of bone resorption by breast cancer cells has attracted some interest, the formation of osteosclerotic secondary tumours and the influence of human mammary carcinoma cells on osteoblasts (bone forming cells), both important in understanding breast cancer--bone interactions, have been largely neglected. We therefore examined the effects of conditioned medium (CM) from two cultured human breast cancer cell lines (MCF7 and ZR-75) and from primary cultures of breast carcinomas from two patients, on osteoblasts and recruitment of bone-resorbing cells (osteoclasts) in vitro. Osteoblast-like cells (BDC) were cultured from human trabecular bone explants. Osteoclast maturation was studied in fetal rat calvaria cultured on collagen gels. CM from the MCF-7 line and cells derived from one patient each inhibited BDC DNA synthesis, but stimulated osteoclast recruitment. In contrast, CM from the second patient's cells or ZR-75 enhanced DNA synthesis in BDC, but blocked osteoclast maturation. This suggests that human breast carcinomas secrete soluble factors which influence both osteoclasts and osteoblasts. A further unexpected implication is that mammary carcinoma cells may cause local osteosclerosis by directly stimulating osteoblasts, rather than through raised bone turnover in metastases.
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PMID:Breast carcinomas synthesize factors which influence osteoblast-like cells independently of osteoclasts in vitro. 200 8

Spontaneous and lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF) by peripheral blood macrophages was investigated in breast cancer. Whereas spontaneous TNF production by macrophages derived from patients with breast cancer was comparable with the one found in healthy controls (P greater than 0.1), LPS-stimulated macrophages derived from patients in the disease-free interval as well as with metastatic breast cancer were found to produce significantly lower amounts of TNF, as compared with macrophages derived from healthy control individuals (P less than 0.0005). However, the production of TNF did not significantly differ between the two patient populations (P greater than 0.05). The impairment of LPS-induced TNF production did not depend upon such characteristics of the primary tumor as size, axillary lymph node and estrogen receptor status, or upon the fact of administration of adjuvant chemotherapy and, in patients with metastatic disease, hormone treatment. To further investigate cytokine production by macrophages, spontaneous and LPS-induced interleukin-1 (IL-1) production was investigated also. However, no difference was found between patients and controls concerning IL-1 generation. The authors thus conclude that LPS-induced TNF production was impaired in breast cancer independent of the presence of detectable metastatic disease, whereas IL-1 production remained unimpaired.
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PMID:Impaired production of tumor necrosis factor in breast cancer. 222 91

Binding of tumor necrosis factor-alpha (TNF-alpha) to its receptor on U937 cells results in rapid and TNF dose-dependent phosphorylation of a cytosolic protein with an apparent molecular mass of 26,000 kDa (p26) and an isoelectric point of 5.6. Half-maximal phosphorylation of p26 was achieved at concentrations of 1.8 ng/ml and was detectable within 20 s of TNF-alpha treatment. p26 is phosphorylated exclusively at serine residues. p26 phosphorylation occurs at 37 degrees C as well as at 14 degrees C, indicating that internalization of the TNF receptor is not required for serine kinase activation. Dephosphorylation of p26 starts 10 min after TNF-induced phosphorylation, suggesting a possible regulatory function of this cytosolic protein within the post-TNF receptor signaling system. p26 is also phosphorylated upon treatment with lymphotoxin. In contrast, both interferon-gamma and lipopolysaccharide fail to induce p26 phosphorylation. Whereas phosphorylated p26 was detected in the TNF-sensitive breast cancer cell line CRL1500, other TNF-responsive tumor cell lines investigated lacked enhanced phosphorylation of p26 in response to TNF, indicating that the 26-kDa phosphoprotein (pp26) may be a cell type-specific second messenger molecule involved in TNF signal transduction in some, but not all, target cells. p26 is also phosphorylated in a subclone of U937 (U937.C27) that responds to TNF-alpha with differentiation, yet is resistant to TNF-alpha-mediated growth inhibition. In contrast, p26 is not phosphorylated in another U937 derivative (U937.G3) that is resistant to both TNF-alpha-induced growth arrest and differentiation, suggesting that pp26 may play a role in the TNF signaling pathway linked to differentiation processes rather than to growth control.
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PMID:Tumor necrosis factor signal transduction. Tissue-specific serine phosphorylation of a 26-kDa cytosolic protein. 253 51

Monocyte derived macrophages from breast and gynecologic cancer patients generally do not acquire enhanced cytotoxicity for human tumor cells after incubation with bacterial lipopolysaccharide (LPS) whereas the macrophages isolated from colon and hematologic cancer patients are cytotoxic. However, it was also found that 75% of the patients possessing cytotoxic macrophages also had a plasma factor which suppressed macrophage mediated cytotoxicity. The plasma inhibitory factor obtained from a colon cancer patient was purified utilizing Sephadex G-200 column chromatography and 4 fractions (A, B, C and D) with inhibitory activity, were isolated. When a plasma sample obtained from a colon cancer patient found to be lacking the inhibitor of macrophage cytotoxicity was fractionated, 2 fractions were isolated with inhibitory activity. These fractions corresponded to fractions A and C of the inhibitory sample. Pooled AB+ serum was also fractionated and no inhibitory fractions could be isolated. The inhibitory factors were further characterized and it was found that fractions A and B appear to be inhibitors of lysosomal enzyme activity and fraction C appears to be an inhibitor of protease activity. When the plasma from cancer patients known to possess an inhibitor of macrophage mediated cytotoxicity was examined for the presence of fraction A, B, C and D, it was found that every colon cancer patient studied possessed inhibitors A, B, C and D. Breast cancer patients possessed some combination of A, B and C but all lacked fraction D and the gynecologic cancer patients possessed some combination of factors A, B and D but they all lacked inhibitor C.
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PMID:Cytotoxicity of cancer patients' macrophages for tumor cells: purification and characterization of plasma inhibitory factors obtained from colon cancer patients. 634 Dec 66

The immunity system condition was studied in 118 patients with breast cancer of stage III who received combination chemotherapy: 91 patients--according to the Cooper scheme and 27 patients--according to CMF scheme. The reaction of lymphocyte blast transformation (LBT) was determined by three mitogens: phytohemagglutinin (PHA "O"), PHA "D" and lipopolysaccharide (LPS). The levels of Ig A, G, M were also determined. A decrease in immunological indices of different degree was observed in all patients. LBT was proved to have a high response to phytohemagglutinin "O" and it is recommended for immunological investigations. No significant changes in the immunological state of LPS were revealed.
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PMID:[Comparative evaluation of the lymphocyte blast-transformation reaction induced by various mitogens in the polychemotherapy of patients with breast cancer]. 649 35

Human monocytes from normal donors as well as breast or colon cancer patients were fractionated on five-step discontinuous bovine serum albumin (BSA) density gradients, and the monocytes from each fraction were allowed to mature into macrophages during a 5 day incubation period. The macrophages were then examined both for their ability to kill tumor cells after activation with lipopolysaccharide (LPS) and the quantity of prostaglandin E2 (PGE2) synthesized. When the macrophages obtained from normal donors were fractionated, fractions 2 and 4 which comprised 58% of the total cell population, were cytotoxic for tumor cells. In contrast, when the macrophages from breast cancer patients were fractionated, only the high density cells found in fraction 4 were cytotoxic. It is also conceivable that since fraction 4 comprises only 26% of the total macrophages recovered, this may be the reason unfractionated macrophages from breast cancer patients are unable to kill tumor cells. When the colon cancer patients' macrophages were fractionated on BSA density gradients, fractions 1, 2 and 4, which comprised 79% of the total cell population, were cytotoxic for tumor cells. Prostaglandin E2 synthesis was also analyzed and it was found that fraction 3 consistently synthesized increased quantities of PGE2 when compared with the other three fractions. Furthermore, since fraction 3 was non-cytotoxic for tumor cells, it is conceivable that the increased synthesis of PGE2 by fraction 3 rendered these macrophages non-cytotoxic.
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PMID:Separation of macrophages on discontinuous bovine serum albumin (BSA) density gradients: cytotoxic effects of fractionated cells from normal donors and cancer patients. 659 30

Cytokines such as interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF alpha), have been identified as important regulators of aromatase activity in fibroblasts derived from normal and malignant breast tissues, and may play an important role in controlling aromatase activity in breast tumours. The major source of such cytokines within breast tumours remains to be established but macrophages and lymphocytes, which can infiltrate tumours, have been identified as a potential source of aromatase stimulatory cytokines. To obtain further insight into the possible role played by the immune system in cancer development, and in particular its ability to regulate aromatase activity via cytokine production, we have obtained peripheral blood monocytes and lymphocytes from an immunosuppressed kidney transplant recipient, receiving cyclosporin A therapy, and a woman with breast cancer. Monocytes and lymphocytes were stimulated with lipopolysaccharide (LPS), and the conditioned medium (CM) collected from these cells was tested for its ability to stimulate aromatase activity in fibroblasts derived from normal breast tissue from a woman undergoing lumpectomy for the removal of a breast tumour. The white blood cell count was lower for the immunosuppressed patient, mainly because of the reduction in the number of monocytes and lymphocytes. The ability of CM from the monocytes and lymphocytes of the immunosuppressed patient to stimulate aromatase activity was significantly reduced (68% and 82% for monocytes and lymphocytes, respectively) compared with that of CM from the cells of the woman with breast cancer. It is possible, therefore, that immunosuppression, which has been found to be associated with a reduction in the incidence of de novo breast cancer in kidney transplant recipients, may exert its effect by inhibiting cytokine production by the cells of the immune system and thus oestrogen synthesis. In contrast to the stimulatory effects that TNF alpha has on aromatase activity in breast fibroblasts, in MCF-7 breast cancer cells, which possess low aromatase activity, it reduced activity. However, the extent of inhibition of aromatase activity in these epithelial cells was much lower than the marked stimulation which it can induce in breast fibroblasts.
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PMID:Control of aromatase activity in breast tumours: the role of the immune system. 936 89

Tamoxifen (TAM) is used in the prevention and treatment of breast cancer, however, its mechanisms of therapeutic action as well as its pathologic effects are not fully understood. We report that TAM (10(-7)-10(-5) M) inhibits 3-methylcholanthrene-induced transformation of C3H 10T1/2 murine fibroblasts in a dose-responsive manner. Over this concentration range, TAM (>10(-6) M) potentiates inducible nitric oxide synthase (iNOS) activity in 10T1/2 cells. This increase in NO synthase activity was mediated through an increase in iNOS protein for cells stimulated with interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS). Significant increases in NO formation were observed when TAM (10(-5)) was added prior to or simultaneously with IFN-gamma/LPS treatment, whereas the addition of TAM 48 h after IFN-gamma/LPS treatment had no effect on NO synthesis. The morphologic changes seen with cells treated with TAM are similar to those observed in cells treated with TGF-beta1. TGF-beta1 inhibited NO production at high doses and slightly enhanced NO formation at low doses in IFN-gamma/LPS-stimulated cells. The transformation inhibitory effects of TAM did not appear to be related to the effects on cellular proliferation of neoplastic cells as TAM did not inhibit the growth of neoplastic cells into foci in the presence of normal confluent C3H 10T1/2 fibroblasts.
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PMID:Effects of tamoxifen on nitric oxide synthesis and neoplastic transformation in C3H 10T1/2 fibroblasts. 946 93


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