UMLS:C0027627 - FACTA Search

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Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the antitumor effects of human recombinant interleukin-6 (hrIL-6) on the highly metastatic B16 melanoma clone F10.9. These tumor cells were found to have very low levels of IL-6 receptors and in vitro IL-6 had no effect on cell proliferation or on the expression of MHC class I antigens. However, in vivo IL-6 was active against the metastatic growth of this tumor in mice, presumably through indirect immune effects. Low-dose IL-6 (1-10 micrograms/day), in three daily injections, 4 days a week, for 3 weeks, strongly inhibited the formation of experimental lung metastases following intravenous tumor cell inoculation. IL-6 therapy could be started even 10 days after tumor injection, when metastases are already established. Moreover, IL-6 treatment of mice bearing F10.9 tumors in the footpads resulted in complete protection against pulmonary spontaneous metastasis and in long-term survival. Histology confirmed the absence of micrometastases in most of the IL-6-treated animals. Analysis of the cytolytic activity of splenocytes at different times during therapy of tumor-bearing mice revealed significant lysis (up to 42%) of the melanoma F10.9 cells in the mice receiving IL-6 but not in the control mice.
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PMID:Abrogation of B16 melanoma metastases by long-term low-dose interleukin-6 therapy. 831 1

Interleukin-2 (IL-2) therapy is dose limited by a severe vascular leak with resulting systemic and pulmonary toxicity. Although recognized as a mediator of septic shock and vascular leak, the relative role of IL-1 in IL-2 toxicity is unclear. We evaluated the effect of IL-1 receptor antagonist (IL-1ra) on IL-2 lethality, pulmonary vascular leak, and treatment of pulmonary metastases in a murine model. In vivo induction of mRNA for IL-1 alpha was evaluated in liver by Northern blots after 0, 5, 8, and 11 doses of IL-2 in C3H/HEN mice. The expression index for the IL-1 alpha gene increased from 0.16 to 0.74 after 5 doses of IL-2, and further increased to 1.04 after 11 doses of IL-2. C3H/HEN mice (n = 56) were randomized to receive phosphate-buffered saline (PBS), IL-1ra high dose (HD), or IL-1ra low dose (LD) by continuous subcutaneous infusion via Alzet mini-pumps. The biologic effectiveness of the dose and administration of IL-1ra was determined by the ability to block IL-1-induced IL-6 production in vivo. Mean serum IL-6 levels 3 hr after intraperitoneal IL-1 alpha (10 micrograms/kg) were: PBS, 3730 +/- 526 (mean +/- SEM pg/ml); IL-1ra (LD), 1156 +/- 398; and IL-1ra (HD), 594 +/- 30 (P < 0.01, IL-1ra HD or LD vs PBS). Pulmonary vascular leak was measured by iv I125 albumin after 8 doses of IL-2 (100,000 U ip q 8 hr).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IL-1 receptor antagonist (IL-1ra) augments IL-2-induced pulmonary vascular leak. 833 27

The production of cytokines by tumor cells has been suggested as the molecular perturbation responsible for the development of malignant tumors. The behavior of tumor cells in animals is presumed to be affected by these factors, which include such hematopoietic cytokines as GM-CSF, IL-1, and IL-6. Here, we report findings demonstrating that GM-CSF is produced by many murine transplantable tumors with metastatic ability in the lungs, and IL-6 and/or IL-1 are produced by the tumors metastatic in the liver. We discuss the notion that the particular organ or organs in which tumor cells metastasize may be associated with the type of cytokines produced by the tumors. Metastatic spread requires interactions of tumor cells with components of the extracellular matrix of host tissues or with other cells, almost all of which depend on cell surface determinants such as cell adhesion molecules. We also discuss the possibility that the expression and adhesive potentials of adhesive protein (CD44) may be regulated by the cytokine (GM-CSF) excreted from the tumor cells. We then emphasize the possibility that both gene expression of cytokines and adhesive proteins play a critical role in tumor metastasis and in determining organ specificity in metastasis.
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PMID:[The roles of cytokine in organ-specific tumor metastasis]. 834 46

In order to evaluate the biological response after intraperitoneal administration of OK-432, we studied the changes of cytokine levels in ascitic fluid. In 6 advanced gastric cancer patients with peritoneal dissemination or extensive lymph node metastases, OK-432 20 KE was administered intraperitoneally during operation and the IL-6, IL-8 and IFN-gamma levels in ascitic fluid were measured from 0 to 5 postoperative days. These results were compared with those obtained from non-OK-432 administered control groups (17 cases). The ascitic level of IL-8 increased immediately after operation and gradually decreased. In the OK-432 treated group, the elevation of IL-8 on 0 and 1 postoperative days was remarkable, and there were statistically significant differences with the control group. Similarly, the ascitic level of IL-6 elevated soon after operation and then decreased gradually. In the OK-432 treated group, the ascitic level of IL-6 was significantly higher than in the control group after 3 postoperative days. There were no differences in changes of ascitic IFN-gamma levels between the groups. From these results, IL-6 and IL-8 appeared to be induced in ascitic fluid by intraperitoneal administration of OK-432.
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PMID:[Changes in cytokine levels in ascitic fluid after intraperitoneal administration of OK-432]. 837 2

We investigated the anti-tumor effects of human recombinant interleukin-6 (hrIL-6) on the highly metastatic Lewis lung-carcinoma clone, D122. These cells express high-affinity IL-6 receptors at numbers comparable to the IL-6-dependent murine hybridoma B9 cells; however, IL-6 did not affect D122 cell proliferation or expression of MHC-class-I antigens in vitro. In vivo, treatment of mice bearing D122 tumors in the footpads, with a low dose of IL-6 in 3 daily injections, 4 days a week for 3 weeks, significantly decreased spontaneous metastases. However, only combined treatment of IL-6 and irradiated tumor cells resulted in almost complete protection against spontaneous metastases. Histological analysis confirmed the absence of micrometastases in most of the animals treated by this combination protocol. Analysis of the cytolytic activity of splenocytes at various time points during combined IL-6 and immunotherapy of tumor-bearing mice revealed significant and sustained lysis of the poorly immunogenic D122 carcinoma cells, while splenocytes of control mice could not lyse D122 target cells. Activation of specific immunity was also demonstrated when mice were pre-immunized with hrIL-6 and inactivated D122 cells and challenged with live carcinoma cells 10 days later. Significant growth inhibition of the primary tumor was observed.
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PMID:Combined therapy with IL-6 and inactivated tumor cells suppresses metastasis in mice bearing 3LL lung carcinomas. 844 6

Adoptive immunotherapy with immune T cells mediates regression of established tumors in animal models. We previously demonstrated that precursor lymphocytes of sensitized T cells can develop into mature effector cells after in vitro activation with anti-CD3 mAb and IL-2. We demonstrate here that tumor cells genetically modified to secrete IL-2 can enhance the precursor response in the tumor-bearing host and subsequently augment the antitumor efficacy of adoptive immunotherapy. MCA205 and MCA203, weakly immunogenic fibrosarcomas, were transfected in vitro with cDNA encoding for IL-2, IL-4, or IL-6. Lymph nodes (LN) draining these cytokine-producing tumors for 7 days were harvested, activated in vitro with anti-CD3/IL-2, and adoptively transferred into mice bearing established parental MCA205 pulmonary metastases. The effector cells generated from LN draining the IL-2 producing tumor exhibited enhanced antitumor activity compared with cells from LN draining parental, IL-4-producing, or IL-6-producing tumor. Phenotype analysis of cells from LN draining the IL-2-producing tumor revealed selective expansion of V beta 8+ cells. Depletion of V beta 8+ effector cells abrogated the antitumor efficacy indicating that V beta 8+ cells constituted the majority of antitumor reactivity and that secretion of IL-2 from tumor cells promoted the priming of V beta 8+ precursor cells, which can develop into mature effector cells. These results have important clinical implications that the method presented here could be applicable to the treatment of human cancer as more effective immunotherapy.
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PMID:Adoptive immunotherapy with tumor-specific T lymphocytes generated from cytokine gene-modified tumor-primed lymph node cells. 862 26

It has been shown that IL-2 and IL-6 can cooperate to induce immune responses more effectively. In order to increase the therapeutic efficacy of cytokine gene-transfected tumor vaccines, we treated the experimental pulmonary metastatic melanoma-bearing mice with IL-2 gene-transfected tumor vaccine and IL-6 gene-transfected tumor vaccine. After the combined treatment, the pulmonary metastases were reduced more significantly and the survival time of tumor-bearing mice was also prolonged more significantly. The CTL activity, NK activity and IL-2-induced LAK activity, IL-2 and TNF secretion from the splenocytes of the above tumor-bearing mice increased more significantly than that of tumor-bearing mice treated with IL-2 gene-transfected vaccine or IL-6 gene-transfected vaccine alone. These results demonstrated that the combined use of IL-2 gene-transfected tumor vaccine and IL-6 gene-transfected tumor vaccine could achieve more potent antitumor effect via more efficient activation of immune functions. The experiment outlines a novel approach to the cytokine gene therapy of cancer.
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PMID:[Antitumor effect of interleukin-2 gene-transfected tumor vaccine in combination with interleukin-6 gene-transfected tumor vaccine]. 869 75

Murine endothelial cells immortalized with the middle-size Ag of polyomavirus (PmT) cause vascular tumors in syngenic mice by recruitment of host normal endothelial cells. This pathogenic process is similar to that occurring in Kaposi's sarcoma, in which the core of the lesion is constituted by "spindle cells," which recruit normal vascular mesenchymal cells. In murine endothelial cells, PmT induces modification of the expression of genes, including that of IL-6. Since IL-6 is a pleiotrophic cytokine that also regulates endothelial cell functions related to angiogenesis, we studied the relevance of IL-6 in the tumorigenicity of PmT-endothelial cells. In vitro studies demonstrated that the spontaneous PmT-endothelial cell proliferation rate was slow during the first 6 days of culture and then increased rapidly and paralleled the IL-6 release. The addition of recombinant IL-6 during the first days of culture induced a marked proliferation in a dose-dependent manner. PmT-endothelial cells expressed on their surface a high-affinity binding site for IL-6 constituted by both IL-6Ralpha and gp130 transmembrane receptors. The growth-promoting effect of exogenous IL-6 or that released by PmT-endothelial cells was abrogated by mAbs anti-IL-6Ralpha, whereas a mAb recognizing the endothelial cell CD31 molecule was inactive. 15A7 mAb anti-murine IL-6Ralpha was also active in vivo, reducing the number of metastases forming after transplantation of PmT-endothelial cells in DBA/2 mice. 15A7 mAb also increased the survival of mice bearing vascular tumors. We conclude that IL-6 is involved in the progression of vascular tumors induced by PmT, and that the blockage of IL-6-mediated intercellular circuits could be useful in the management of human vascular tumors, including Kaposi's sarcoma.
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PMID:IL-6 is an in vitro and in vivo autocrine growth factor for middle T antigen-transformed endothelial cells. 880 65

At present, it is known that there are two main mechanisms responsible for cancer-related immunosuppression, mediated by macrophages and by TH2 lymphocytes. The relation existing between macrophage- and TH2-mediated immunosuppression still remains to be understood. The present study was performed in an attempt to establish which is the correlation existing in cancer patients between IL-10 and neopterin levels, which reflect TH2- and macrophage-mediated suppressive events, respectively. The study included 40 solid tumor patients and 60 healthy subjects as controls. Serum concentrations of neopterin and IL-10 were measured by the RIA method and by an immuno-enzymetric assay, respectively. Because of its possible production both by TH2 and macrophages, serum levels of IL-6 were also determined. Neopterin, IL-10 IL-6 mean concentrations were significantly higher in cancer patients than in controls. Mean values of both neopterin and IL-6 were significantly higher in metastatic patients than in those with locally limited disease. IL-10 mean levels were also significantly higher in patients with metastatic disease. IL-6 levels were significantly correlated with those of neopterin, whereas no correlation was found between neopterin and IL-10 values. This preliminary study would suggest that macrophage- and TH2-mediated immunosuppression may occur independently in solid tumors, and that it becomes more evident with disease progression.
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PMID:Relation between macrophage and T helper-2 lymphocyte functions in human neoplasms: neopterin, interleukin-10 and interleukin-6 blood levels in early or advanced solid tumors. 884 39

The extensive mortality and morbidity associated with prostate cancer is caused by the high prevalence of metastatic disease at the time of diagnosis. The area most frequently involved in metastatic prostate cancer is the skeleton. Unlike other cancers, which metastasize to bone and destroy the bone matrix, prostate cancer is unique in that it is osteogenic, resulting in the formation of dense, sclerotic bone with high levels of osteoblastic activity. We proposed that factors produced by bone cells may be responsible for the development of prostate carcinoma metastasis. We studied the effects of these growth factors on prostate cell proliferation by [3H]thymidine incorporation and chemotaxis by the double-filter chamber method. Three prostate carcinoma cell lines were studied, LNCaP (androgen responsive) and PC-3 and DU-145 (androgen unresponsive). The bone-associated growth factors tested were: insulin-like growth factors I and II (IGF-I, IGF-II), transforming growth factor beta, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha), IGF-I and IGF-II significantly increased proliferation in all three cell lines, whereas IL-6, TNF-alpha, and IL-1 beta significantly decreased proliferation. Transforming growth factor beta induced a biphasic response in proliferation in DU-145 and PC-3 cells and produced no response on LNCaP cells. Increased cell chemotaxis occurred in the presence of IGF-I and IGF-II, and decreased cell chemotaxis occurred with the addition of TNF-alpha and IL-1 beta. These data indicate that growth factors produced by bone cells alter prostate carcinoma cell proliferation and chemotaxis and suggest that modulations of the production of these factors may be a potential therapeutic intervention in deterring the metastasis of prostate carcinoma to bone.
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PMID:The effects of growth factors associated with osteoblasts on prostate carcinoma proliferation and chemotaxis: implications for the development of metastatic disease. 904 21

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