Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using peritoneal fluid or pleural effusion obtained from 20 patients with lung, ovarian or metastatic breast cancer, we separated tumour cells from malignant effusion-associated mononuclear cells (MEMNCs) using discontinuous Ficoll-Hypaque density gradients. CD3+ T lymphocytes represented the main population of MEMNCs. The mean +/- s.d. CD4/CD8 ratio of MEMNC suspensions was 1.18 +/- 0.40. MEMNCs proliferated and expanded in vitro with human interleukin 2 (IL-2) either as CD3+ CD8+ cells or as CD3+ CD4+ cells or as mixed populations of CD8+ and CD4+ cells. Preferential cytolytic activity against autologous tumour cells was demonstrated in IL-2-activated MEMNC cultures with excess CD3+ CD8+ cells. In contrast, effectors derived from IL-2-activated cultures with excess CD3+ CD4+ cells lysed both autologous and allogeneic tumour target cells. The addition on day 0 of interleukin 1 beta (IL-1 beta) to MEMNCs cultured in the presence of IL-2 was effective in promoting the growth of CD3+ CD8+ cells and augmenting the cytotoxicity against autologous tumour. Simultaneously, the production of gamma-interferon (IFN-gamma) was increased in these cultures. This is the first report suggesting that IL-1 beta synergises with IL-2 to induce autologous tumour-specific CD8+ cytotoxic T lymphocytes (CTLs) within the MEMNC population. Selective enrichment in T-cell subsets by IL-1 beta may be useful in cellular adoptive immunotherapy using cells isolated from malignant effusions.
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PMID:Interleukin 1 beta synergises with interleukin 2 in the outgrowth of autologous tumour-reactive CD8+ effectors. 791 7

We studied the effects of escalating doses of recombinant human IL-1 beta in patients receiving high-dose chemotherapy and ABMT for metastatic breast cancer or malignant melanoma. Sixteen patients received IL-1 beta, 4 to 32 ng/kg/day administered subcutaneously for 7 days beginning 3 h after bone marrow infusion. Three patients at the highest dose level also received G-CSF following completion of IL-1 beta. All patients completed the 7 days of therapy. The majority of patients experienced chills and fever following one or more injections, and seven had severe pain at the injection site. There was one episode of hypotension and one episode of transient confusion at the highest dose level; other significant toxicity was not identified. Recovery of neutrophils to > 0.5 x 10(9)l and platelet transfusion independence occurred at a median of 23 and 22 days, respectively, which was comparable to historical controls. The mean number of bone marrow colony-forming unit granulocyte-macrophage (CFU-GM) per 10(5) mononuclear cells on day +21 post-ABMT was more than twice that of control patients or patients receiving G-CSF or GM-CSF. A linear correlation was found between the dose of IL-1 beta and endogenous concentrations of several cytokines. These patients also displayed significantly higher concentrations of endogenous G-CSF compared to historical controls receiving GM-CSF. While IL-1 beta was moderately toxic and had no effect on recovery of peripheral blood counts after ABMT, the increased number of bone marrow CFU-GM suggests that the addition of G- or GM-CSF to a short course of IL-1 beta may accelerate hematologic recovery.
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PMID:A phase I trial of recombinant human interleukin-1 beta (OCT-43) following high-dose chemotherapy and autologous bone marrow transplantation. 905 Dec 40

Serum concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, IL-2 and IL-6 were determined by enzyme-linked immunosorbent assay or chemiluminescent enzyme immunoassay in 46 Japanese patients with metastatic breast cancer. No IL-2 activity was detectable, only two patients had a detectable TNF-alpha level, and 4 had detectable IL-1 beta concentrations. No correlations were found between TNF-alpha and IL-1 beta levels and clinicopathological parameters. Twenty-two patients (48%) showed higher serum IL-6 levels than the cut-off value of 4 pg/ml. Significantly higher IL-6 levels were detected in patients with more than one metastatic site and with dominant metastatic visceral disease than in those with one metastatic site (median, 6.9 vs 1.1 pg/ml, P < 0.0001) or with dominant metastatic bone or soft tissue disease (median, 7.1 vs 2.4, P < 0.05). The patients with liver metastasis and pleural effusion showed significantly higher serum IL-6 levels than those without liver metastases (median, 17.2 vs 2 pg/ml, P = 0.0006) or pleural effusion (median, 12.1 vs 2.1 pg/ml, P = 0.02). A strong correlation was observed between IL-6 levels and C-reactive protein levels (r = 0.47, P = 0.0006). Patients unresponsive to chemo-endocrine therapy showed significantly higher serum IL-6 levels than those who responded to chemo-endocrine therapy (P = 0.0007). Moreover, the patients with high IL-6 levels showed significantly poorer survival than patients with low IL-6 levels. Multivariate analysis revealed that IL-6, as well as disease-free interval, is an independent prognostic factor of metastatic breast cancer. These results suggest that IL-6 levels are elevated and may be an aggressive parameter in patients with metastatic breast cancer. Higher IL-6 serum levels are found to predict a poorer response to chemo-endocrine therapy, and to represent a poorer prognostic predictor in metastatic breast cancer.
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PMID:Serum interleukin-6 levels correlate to tumor progression and prognosis in metastatic breast carcinoma. 1036 18