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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent clinical and experimental studies have focused on the measurement of cytokines and their regulators, produced by immunocompetent cells. Their estimation may be used as parameters for the immune potential of cancer patients. In the present study we studied the ability of unstimulated and lipopolysaccharide (LPS)-stimulated polymorphonuclear cells (PMN) and peripheral blood mononuclear cells (PBMC) from oral cavity cancer and breast cancer patients to release tumor necrosis factor alpha (TNF-alpha) and soluble tumor necrosis factor receptors (sTNFR). There were significant differences concerning the parameters examined for PMN and PBMC from cancer patients as compared with normal subjects. We found significantly higher concentrations of sTNF-R p75 than sTNF-R p55 in the cell-culture supernatants. The culture supernatants of cells from oral cavity cancer patients contained higher concentrations of TNF-alpha and lower concentrations of sTNF-R p55 and sTNF-R p75 in comparison with breast cancer cell supernatants. In contrast, cells from breast cancer patients secreted lower concentrations of TNF-alpha and higher concentrations of sTNF-R p55 and sTNF-R p75. Although PBMC secreted higher concentrations of mediators than PMN, the quantitative dominance of PMN in the peripheral blood suggests an essential role of these cells in the defense reactions controlled by TNF-alpha.
Eur Cytokine Netw 1998 Jun
PMID:Tumor necrosis factor-alpha and soluble tumor necrosis factor receptors in the culture supernatants of polymorphonuclear cells and peripheral blood mononuclear cells from cancer patients. 968 91

Although tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) can stimulate each others activity and induce similar effects on distinct cells, soluble TNF-receptors (sTNF-RI and sTNF-RII) and soluble IL-6 receptor, exhibit a significant differences in their functional activity. In this study the authors investigated the concentrations of sTNF-Rs and sIL-6R in the culture supernatants of PMNs and in the serum obtained from breast cancer patients. Soluble TNF receptors in patients before treatment were higher than in control and decreased following the surgery treatment. Soluble IL-6 receptor was decreased in patients before treatment and elevated following the surgery treatment. Sera from patients presented increased the levels of sTNF-Rs and sIL-6R with respect to control. Chemotherapy treatment resulted in a decrease in the serum levels of sTNF-Rs and sIL-6R. There was a correlation between the amounts of sIL-6R in the culture supernatants of PMNs and the serum levels. Results obtained confirm the effective participate of PMNs in the immune reactions to tumour.
Cytokine 1998 Jul
PMID:Changes in sIL-6R and sTNF-Rs release by PMNs and the serum levels in breast cancer patients at different stages of treatment. 970 18

In the present study, we isolated tumor-infiltrating lymphocytes (TIL) from 21 primary solid tumors and tumor-associated lymphocytes (TAL) from 9 malignant effusions, respectively, of breast cancer patients. Significant proliferation and expansion of T cells was observed in 23 of 30 distinct samples. TIL were isolated from primary tumors by either enzymatic digestion or mechanical disruption. The TIL cultures were initiated using OKT3 mAb in the presence of moderate concentrations (25-50 U/ml) of IL-2, followed by 100 U/ml of tumor necrosis factor (TNF)-alpha. TAL were not stimulated with OKT3 mAb, but all were successfully expanded in culture in the presence of IL-2 alone or together with TNF-alpha. Seven of nine distinct TAL grew in culture as predominantly CD4+ lines. In contrast, only 14 of 21 (66%) of primary breast TIL expanded in culture and were predominantly of CD8+ phenotype. Autologous tumor lysis was observed in seven of eight cases tested. Only one of the four TIL tested and one of the four TAL tested preferentially lysed autologous tumor. HER-2 peptide E75 (369-377) was recognized by two TIL lines of the five primary TIL tested and three of the four TAL tested. This suggests that E75 may be recognized by primary breast tumors. This may be of interest in developing vaccine strategies for therapeutic management of breast cancer.
J Interferon Cytokine Res 1998 Jul
PMID:Growth and antigen recognition of tumor-infiltrating lymphocytes from human breast cancer. 971 69

Interleukin 6 (IL-6) is a pleiotropic inflammatory cytokine and its role in cancer is not yet clear. The effects of IL-6 on four breast cancer cell lines and normal mammary epithelium, cultured from milk were tested. Four different patterns of response to IL-6 were found depending on the differentiation status of the cells. In normal mammary epithelial cultures, the effects of IL-6 were mainly growth inhibitory, whereas in MCF-7, IL-6 had growth inhibitory and anti-adhesive effects. In T-47D and ZR-75-1 the anti-adhesive effects were prominent although the growth inhibitory effects were not. These anti-adhesive effects were associated with epithelioid to fibroblastoid morphological changes and a local decrease in E-cadherin expression. In the highly invasive cell line MDA-MB-231, which does not express E-cadherin, no effects of IL-6 were seen. IL-6 levels in the serum of 60 breast cancer patients were found to be increased in 27% (16/60) compared to 2% (1/50) in a control group. Furthermore, it was found that altered E-cadherin expression was seen in 69% of the primary tumours, although no significant association was found between raised serum IL-6 levels and altered E-cadherin expression. Finally IL-6 serum levels did not effect the survival of breast cancer patients. The authors therefore implicate IL-6 as a possible factor important in breast cancer progression and metastasis formation, although the clinical significance of this cytokine in breast cancer patients could not be established.
Cytokine 1998 Sep
PMID:The effects of IL-6 on cell adhesion and e-cadherin expression in breast cancer. 977 Mar 34

The effects of gastric and breast cancer surgery on the systemic immune response, and potential correlations with cytokines in peritoneal fluid (PF) and wound fluid (WF) after surgery were investigated in humans. Twenty patients with gastric cancer and 13 patients with breast cancer were studied. Blood natural killer (NK) cell activity and serum soluble interleukin-2 receptor (sIL-2R) were assayed, and prostaglandin E2 and transforming growth factor-beta1 were measured in PF and WF. A prolonged decrease in NK cell activity was observed after gastrectomy compared with mastectomy. Serum sIL-2R levels were increased after gastrectomy, whereas no difference was observed after mastectomy. Cytokine levels in PF persisted on day 1 through 5 after gastrectomy, whereas in WF they dropped sharply on postoperative day 3. The systemic immune response was decreased longer after gastrectomy than mastectomy, and this immune modulation may be partly attributable to the presence of cytokines in local exudates.
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PMID:Release of immunosuppressive substances after gastric resection is more prolonged than after mastectomy in humans. 987 Jul 76

The aim of the present study was to compare the biological effects of 12 different clinically applied mistletoe preparations (I, II, III and IV) from the host trees "pinus" (P), "malus" (M), "abies" (A) and "quercus" (Q) on human leukocytes. When the preparations I-P, II-P, III-P and IV-A were added to the whole blood cell cultures of 37 cancer patients (breast cancer, n = 22, colorectal cancer, n = 15) and 34 healthy controls, a significant induction of the cytokines IL-1-beta, IL-2, IL-6, IL-10 and TNF-alpha was found with preparation I-P. A significant induction of IL-1-beta and TNF-alpha was obtained with the preparations II-P and III-P as compared to the nonstimulated control cultures. Induction of IFN-gamma was not found with any preparation. Cytokine induction was comparable in the blood cell cultures of the tumor patients and the healthy controls. When the clinical preparations I-P, I-M, I-Q, II-P, II-M, II-A, III-P, III-M, III-A and IV-P, IV-M, IV-A were tested in cultures of peripheral blood mononuclear cells from 5 healthy donors, differences in the induction of cytokine production and apoptosis were seen after addition of the mistletoe preparations from different host trees. Increased levels of IL-1-beta were found after addition of the preparations I-P and I-M, increased levels of TNF-alpha were measured after addition of preparations I-P and III-A. Induction of apoptosis was most evident with the preparations I-M, I-Q, III-M and IV-A. Neither cytokine induction nor apoptosis could be correlated to the amount of lectins found in the preparations. Stimulation of separated CD4(+)-, CD8(+)- and CD14(+)-cells from 5 healthy donors with the above noted preparations revealed an induction of IL-1-beta and TNF-alpha production by the preparations I-P, I-M and I-Q mainly in monocytes and to a minimal extent in lymphocytes. Also apoptosis was seen mainly in CD14(+)-monocytes. From these results it is concluded that both, apoptosis and cytokine production are induced differentially in leukocyte cultures by clinically applied mistletoe preparations. However, there is no correlation between the biological effects and the lectin content of the various preparations and none of them were comparable with respect to the extent of these effects. Therefore, it may be expected that clinical studies with different preparations are not comparable either.
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PMID:Comparison of the effects of various clinically applied mistletoe preparations on peripheral blood leukocytes. 989 35

A clinical randomized study was performed on advanced breast cancer patients who were treated by interferons (IFN) beta and gamma in combination with hormonotherapy (Megace or Tamoxifen). Cytokine levels (IL-1beta, IL-2, IL-6, TNF-alpha, IFN-gamma) and sIL-2R of individual patients before, during (3 months) and after (6 months) therapy were evaluated and correlated to clinical response according to UICC criteria (responder patients-partial or Complete Response versus non-responder patients-Stable/Progression). Decreases in IL-1beta, IL-6 and sIL-2R were associated with clinical response to therapy versus increases in their levels which corresponded to progression of disease. A significant and dramatic increase in IFN-gamma levels was associated with a favourable response to therapy in the IFNs-treated patients, mainly in the group of Tamoxifen. Baseline levels of sIL-2R and of IFN-gamma were prognostic of clinical response and were found to be the most sensitive cytokine parameters for defining the clinical utility of the combination of IFNs and hormonotherapy in breast cancer patients.
Cytokine 1998 Dec
PMID:Changes in cytokine production of breast cancer patients treated with interferons. 1004 22

Lymph nodes can be the primary target of infection or malignant transformation and may exhibit characteristic patterns of leukocyte infiltration analogous to those seen in inflammation of other tissues. Leukocyte migration to lymph nodes in vivo is a highly regulated, multi-step process that depends upon adhesion molecules and as yet, uncharacterized chemotactic signals. Chemokines are a key part of the orchestrated code of signals that directs leukocyte subsets to sites of inflammation or immune response. The potential role of these chemoattractants in selective trafficking of leukocyte subsets into lymph nodes was assessed by determining the expression of chemokines on a range of pathological and normal human lymph nodes and by evaluating the cellular composition of each lymph node. In situ hybridization using chemokine riboprobes and immunohistochemistry using specific antibodies were performed in order to correlate the mRNA and protein expression of the chemokines. The cellular source(s) of each chemokine was assessed by immunohistochemical staining of adjacent sections using antibodies directed against distinctive cellular markers. Substantial, but varied, expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, RANTES, macrophage chemotactic protein (MCP)-1, eotaxin, and interleukin 8 (IL-8) were detected in the pathological lymph nodes by diverse cell types. Control lymph nodes showed expression only of RANTES, mainly by high endothelial venules. In all lymph nodes, except the nodes infiltrated with breast cancer, chemokine mRNA expression was highly concordant with the corresponding protein. In contrast with in vitro studies that have suggested discrete target cell specificity of chemokines, this study showed that with the possible exception of the neutrophil chemoattractant, IL-8, no chemokine appeared to be uniquely associated with the accumulation of a specific leukocyte subset. These data implicate chemokines in the recruitment of leukocytes to lymph nodes affected by diverse disease states.
Cytokine 1999 Jul
PMID:Abundant expression of chemokines in malignant and infective human lymphadenopathies. 1041 55

The most frequent site of breast cancer metastasis is bone suggesting that some breast cancers express proteins that facilitate this process. We evaluated whether a highly metastatic breast cancer cell line, MDA-MB-231, and a less metastatic breast cancer cell line, MCF-7, contain bone morphogenetic proteins (BMP). Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that MDA and MCF-7 cells contain mRNAs for BMP receptors IA, IB and II. RT-PCR indicated the presence of mRNAs for BMPs 2 and 3 but not 4 and 7 in breast cells. Using a RT-PCR strategy with molecular beacons, we found that the mRNA for BMP2 in MDA cells was decreased by 75% after a sublethal dose of radiation. An ELISA using an antibody specific for BMP2 demonstrated that BMP2 protein was reduced after radiation of MDA cells. The mRNA for BMP2 was expressed to a lesser extent in MCF-7 cells than MDA cells and was not altered after radiation treatment of MCF-7 cells as demonstrated by molecular beacon RT-PCR. Recombinant human BMP2 decreased the proliferation of MDA cells to a greater extent than MCF-7 cells. These results expand the number of tissues that contain BMPs and demonstrate the effect of this signalling pathway of the growth state of these tissues.
Cytokine 1999 Dec
PMID:Identification of bone morphogenetic proteins and their receptors in human breast cancer cell lines: importance of BMP2. 1062 28

A trial was conducted to investigate whether the sequential administration of recombinant human granulocyte colony-stimulating factor (G-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) could accelerate reconstitution of hematopoiesis, compared with G-CSF alone following high-dose chemotherapy (HDCT). A group of 34 consecutive patients with solid tumors undergoing HDCT and autologous peripheral blood progenitor cell (PBPC) transplantation was studied. Conditioning regimen included carboplatin, etoposide, mitoxantrone, and melphalan for breast cancer and cyclophosphamide or ifosfamide, carboplatin, and etoposide for the other tumors. HDCT was delivered from day -3 to day -1. PBPC were infused on day 0, and on the same day growth factors were administered subcutaneously (s.c.) 5 microg/kg each. Seventeen patients were randomized to receive G-CSF from day 0 to day 13 after HDCT (arm A), and 17 patients received G-CSF from day 0 to day 6 and GM-CSF from day 7 to day 13 (arm B). Patients were stratified, and their characteristics were homogeneous in both arms for age, performance status, and number of previous chemotherapy courses and CD34+ infused. The median time to absolute neutrophil count (ANC) >500/microl was 10 days in arm A and 9 days in arm B (p = 0.96). Days to platelet (PLT) count >20,000 were not different in the two treatment arms (p = 0.1), but patients randomized to arm A had a lower platelet count compared with patients in arm B. One month after PBPC transplantation, a statistically significant difference in PLT count was observed (arm A median 150x10(3)/microl (90-310), arm B median 254x10(3)/microl (117-387),p = 0.0013). The days patients had fever >38 degrees C were 39 in arm A and 26 in arm B (p = 0.18). The difference in the length of hospital stay was not statistically significant between the groups (Mann-Whitney sum rank test). After a median follow-up of 30 months, 21 patients were alive and 20 were disease free. These data show that the two growth factors are associated with different patterns of hematopoietic recovery, and larger randomized trials in groups of more homogeneous patients will be needed to define the effects and benefits of combination growth factor therapies.
J Interferon Cytokine Res 2000 Feb
PMID:Randomized trial of sequential administration of G-CSF and GM-CSF vs. G-CSF alone following peripheral blood progenitor cell autograft in solid tumors. 1071 52


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