Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study reports on biological response modification induced by prolonged continuous subcutaneous (s.c.) infusion of recombinant interferon-gamma (rIFN-gamma) with particular attention to changes of soluble CD14. This glycoprotein with an unknown function is derived from myeloid cells carrying membrane CD14, which is the receptor for lipopolysaccharide (LPS)-LPS-binding protein (LBP) complexes. Fifteen metastatic cancer patients received weekly escalating doses of rIFN-gamma starting at either 50 or 100 micrograms/24 h and increasing up to 400 micrograms/24 h for a median duration of 6 weeks. The maximum tolerated dose was higher (200 micrograms/24 h) with the lower (50 micrograms/24 h) starting dose. Biological activity of rIFN-gamma was evaluated by weekly measurements of CD14, neopterin, and beta 2-microglobulin concentrations in serum as well as monocyte HLA class I and II antigen expression and tumor cytotoxicity. Serum IFN-gamma concentrations increased 20-fold within 4 weeks of therapy. The levels were correlated to the mean dose (r = 0.95, p less than 0.05). Among the biological markers, two patterns were observed. First, serum CD14 concentration and expression of monocyte HLA class II antigens increased significantly during the first week, and marker expression correlated with serum IFN-gamma levels (p less than 0.05); CD14 and HLA class II antigens thereafter returned to pretreatment levels within 4 weeks of therapy despite persistently elevated serum IFN-gamma concentrations. Second, serum neopterin and beta 2-microglobulin concentrations as well as monocyte HLA class I expression also increased significantly within the first week, but remained elevated thereafter without any further dose relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prolonged interferon-gamma application by subcutaneous infusion in cancer patients: differential response of serum CD14, neopterin, and monocyte HLA class I and II antigens. 137 54

We have previously reported that abdominal irradiation of mice inhibited lung metastases of a weakly immunogenic fibrosarcoma, and that transmigration after the irradiation of Enterobacter cloacae into mesenteric lymph nodes coincided with this phenomenon. In this paper, we show that Escherichia coli as well as E. cloacae reduce the number of metastatic lung colonies when these bacteria were intravenously injected into mice prior to the tumour cell challenge. The inhibition was caused not only by the administration of living bacteria but also by that of killed bacteria. Bacterial lipopolysaccharide (LPS), a component of membrane, replaced at least in part the effect of whole bacteria. Transfer of spleen cells from LPS-treated mice into intact recipients prominently inhibited metastatic development in the recipient mice. 'Cross transfer' between LPS high responders and LPS low responders suggested an indirect activity of transferred spleen cells. The antimetastatic activity of LPS depended on the tumour cell type; metastasis of fibrosarcomas was extensively inhibited by LPS irrespective of tumour immunogenicity while that of adenocarcinomas was only slightly inhibited. These results suggest that non-immunological mechanisms are involved in the antimetastatic activity of LPS.
Clin Exp Metastasis
PMID:Active components of intestinal bacteria for abdominal irradiation-induced inhibition of lung metastases. 175 83

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

Alveolar macrophage function in patients with renal carcinoma, a disease characterized by frequent pulmonary metastases, has not been examined. The purpose of this study was to evaluate tumoricidal responses of alveolar macrophages in renal carcinoma to determine if such activity is compromised. Alveolar macrophages and/or blood monocytes were obtained from 26 normal volunteers and 16 patients with renal carcinoma. Tumoricidal activity of alveolar macrophages and monocytes was assessed against 3H-thymidine-labeled tumor target cells. Patient alveolar macrophages and monocytes exposed to lipopolysaccharide (LPS) or recombinant interferon-gamma expressed tumoricidal activity comparable to those in normal subjects. Activated alveolar macrophages recognized and lysed neoplastic cells (including allogenic renal carcinoma cells), but not nonneoplastic cells. Alveolar macrophage and monocyte tumoricidal responses of patients with pulmonary metastases were not different from those of patients with metastases to other sites. These results indicate that alveolar macrophages from patients with renal carcinoma with or without pulmonary metastases are not compromised in vitro, but respond to immunomodulators with enhanced tumoricidal activity in the same fashion as do alveolar macrophages from normal volunteers.
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PMID:Immunologic studies of alveolar macrophages from patients with metastatic renal cell carcinoma. 233 45

For the purpose of inducing the antitumor effect in the portal vein, the intrasplenic serial biological response modifier (BRM) administration was performed by using our original subcutaneously-imbedded pediculated spleen in the rats. In a view point of endogenous tumor necrosis factor (TNF) production, lipopolysaccharide, BCG and OK-432 were chosen and injected into the spleen frequently. The study of the portal blood serum revealed that intrasplenic (i.s.) BRM administration group gained higher TNF and interferon (IFN) activity than control group. On the other hand, the study of the mononuclear cells in the portal vein and splenocyte after i.s. BRM administration showed higher cytotoxic activity against YAC-1 cells than control group significantly. Compared with intravenous and intraperitoneal administration groups, i.s. group showed more effective antitumor effects in the portal vein significantly. The experimental liver metastases by intraportal transplantation of AH60C could be cured with i.s. BRM administration, which could increase % survival significantly. According to the result of this study, it is prospective that i.s. serial BRM administration could be new process for suppression of transportal hepatic metastases.
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PMID:[Induction of endogenous antitumor activities in the portal vein by using a subcutaneously-imbedded pediculated spleen in the rat; experimental study of adjuvant immunotherapy in liver metastases]. 246 67

We have investigated the endogenous production of a serum cytotoxic factor when recombinant interferon-gamma (rIFN-gamma) is combined with synthetic lipid A subunit analogs of low toxicity (GLA compounds). The cytotoxic activity of the serum was measured by the crystal violet staining method with L929 cells as a target. Intravenous administration of rIFN-gamma followed by intravenous administration of lipopolysaccharide induced the endogenous production of a cytotoxic factor in the serum. The priming effect of rIFN-gamma appeared immediately and persisted for approximately 20 h after the injection. Administration of lipopolysaccharide as a trigger enhanced the production of the cytotoxic factor in the serum maximally 2 h after the injection. The cytotoxic activity in the serum was completely inhibited by anti-(mouse tumor necrosis factor) (TNF) antibody. A synthetic lipid A subunit analog (GLA-60), which is much less toxic in its endotoxin activities than lipopolysaccharide or synthetic lipid A (compound 506), induced the endogenous production of serum TNF in rIFN-gamma-primed mice. GLA-60 entrapped within liposomes induced the production of serum TNF in rIFN-gamma-primed mice more effectively than GLA-60 solubilized in phosphate-buffered saline. Intravenous or intranasal administrations of rIFN-gamma followed by intranasal administration of GLA-60 produced TNF in the lung washing fluid but not in the serum, indicating that TNF production can be induced locally rather than systemically by the alteration of the administration route of the primer and trigger. These results indicate that GLA-60, a lipid A subunit analog of low toxicity, is a beneficial triggering agent in the production of endogenous TNF, as well as having other immunopharmacological properties, and may provide a basis for cancer (metastases) treatment as a result of its ability to induce endogenous TNF.
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PMID:Induction of an endogenous tumor necrosis factor in mice by murine recombinant interferon-gamma combined with a lipid A subunit analog (GLA-60) of low toxicity. 249 79

Kupffer cells (KC) are believed to play a major role in protecting the liver from metastases. In vitro, activated KC mediate both tumor cell cytostasis and cytolysis. Because hepatocytes (HC) occupy a position adjacent to KC in vivo, we investigated the influence of HC on KC tumoricidal activity. Using an in vitro assay of KC-mediated tumor cell cytostasis against murine P815 mastocytoma cells, we found that the presence of HC in the culture profoundly increased KC tumoricidal activity. HC enhanced KC inhibition of P815 proliferation and lowered the concentration of lipopolysaccharide and interferon-gamma necessary to activate the KC to a tumoricidal state. This stimulatory HC effect was dependent on the number of HC present and was transferable in cell-free supernatants, indicating that it was mediated by a soluble secreted product of HC. Furthermore, unlike other macrophage-priming or -potentiating factors, the transferable HC factor(s) was effective only if added simultaneously with lipopolysaccharide or interferon-gamma and not effective if added before these activating agents. These data show that HC produce a soluble mediator that enhances KC tumoricidal activity, suggesting that HC and KC interactions may be critical to the antitumor defense mechanisms of the liver.
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PMID:Hepatocytes enhance Kupffer cell-mediated tumor cell cytostasis in vitro. 250 99

Interleukin-1 (IL-1) release by alveolar macrophages (AMs) from 29 patients with primary bronchogenic carcinoma, lung metastases, acute pneumonitis, and chronic infection was evaluated in response to a standard stimulus, lipopolysaccharide (LPS). The results were compared to those of AMs from normal smokers or nonsmokers (volunteers). AMs derived from healthy smokers secreted significantly more IL-1 than AMs from nonsmokers. In contrast, AMs from smokers affected with primary lung cancer have lost their capacity of secreting high levels of IL-1, whereas IL-1 secretion was high in nonsmokers with hematogenous metastases. AMs release high IL-1 levels in patients with acute bacterial infections. A significant correlation exists between numbers of AMs and IL-1 levels in normal individuals, a relationship which disappears in patients. These observations suggest that AMs in inflammatory lung disease, even discrete, have an increased capacity to secrete IL-1 on stimulation with LPS. They also suggest that an intrinsic dysfunction of AMs may accompany primary bronchogenic carcinoma. The influence of tobacco in modifying the functions of AMs is stressed.
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PMID:Interleukin-1 secretion by lipopolysaccharide-stimulated alveolar macrophages. Relationships to cell numbers--influence of smoking habits. 281 73

Infectious respiratory diseases in man and in domestic animals are characterized by the presence of a large number of different microorganisms: viruses, bacterias, mycoplasmas. It is therefore necessary to stimulate non-specific defense mechanisms in the lung and especially alveolar macrophages (AM). These cells, located in the alveolar air-spaces, play a major role in the lung clearance mechanisms and exert antibacterial, antiviral and antitumoral activities. Activation of alveolar macrophages was studied in vitro with lipopolysaccharide (LPS), lymphokines or mycobacterial derivatives (MDP). Rodent alveolar macrophages were rendered cytotoxic by in vitro exposure to LPS, free MDP or liposome-encapsulated MDP derivatives. In vivo, intravenously administered liposomes containing lipophilic MDP derivatives induced cytotoxic alveolar macrophages and protected mice against the development of pulmonary metastases.
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PMID:Effects of immunopotentiating agents on alveolar macrophage properties. 353 92


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