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)

We investigated the immunomodulatory capacity of primary cultures of renal cell carcinomas (RCC) by assessing production of cytokines and modulation of mitogen-induced T lymphocyte blast transformation. The results clearly show that immunomodulatory capacity is a common feature of RCC and that in vitro these tumors can produce interleukin-10 (IL-10) up to 20 ng/ml, IL-6 up to 35 micrograms/ml (> 250 kU/ml in the B9 system), IL-11 up to 15 micrograms/ml, and transforming growth factor-beta 1 (TGF-beta 1) up to 22 ng/ml. Furthermore, these tumors have the capacity to modulate T cell blast transformation over two orders of magnitude in each direction. The correlations of the immunologic properties of tumor cell cultures with the conventional classification of tumors (histology, cytology, staging, grading, presence of metastases, and secondary tumors) are analyzed. The significance of these findings for modulation of local immunity by RCC as well as for patient outcome is discussed.
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PMID:Renal cell carcinomas produce IL-6, IL-10, IL-11, and TGF-beta 1 in primary cultures and modulate T lymphocyte blast transformation. 905 15

IL-2 and IL-6 are important cytokines which have potent antitumor effects and can cooperate to induce immune responses more effectively. IL-2 gene or IL-6 gene-transfected tumor cells exhibited reduced tumorigenicity and decreased metastatic potential. In order to increase the therapeutic efficacy of IL-2 gene-, IL-6 gene-modified tumor vaccines, the experimental pulmonary metastatic melanoma-bearing mice were treated with inactivated IL-2 gene-transfected tumor cells and inactivated IL-6 gene-transfected tumor cells. After the combined vaccination, the pulmonary metastases were reduced more significantly and the survival time of tumor-bearing mice was also markedly prolonged. 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 vaccinated 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 effective activation of specific and non-specific antitumor immune responses.
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PMID:Enhanced efficacy of combination of IL-2 gene and IL-6 gene-transfected tumor cells in the treatment of established metastatic tumors. 915 3

Cell motility is an important factor in the process of invasion and metastasis of tumor. In this study, the relationship between cell motility and experimental metastatic potential was examined using two human pancreatic cancer cell lines, SW1990 and PANC-1. Serum-free conditioned medium from the highly metastatic cell line SW1990 was found to contain a factor that stimulated the migration of and induced a fibroblast-like morphological change in the weakly metastatic cell line PANC-1. Preincubation of PANC-1 cells with SW1990 conditioned medium (SW-C.M.) induced liver metastasis following splenic injection of PANC-1 cells in nude mice, although no liver metastasis was observed without pretreatment of SW-C.M. This factor, temporarily termed PDMF (pancreatic cancer-derived motility factor) is a heparin non-binding protein having a molecular weight of 40 kDa calculated by gel-filtration HPLC which acts not only chemotactically but also chemokinetically, and also acts mainly in a paracrine fashion. However, this factor had no effect on the proliferation of PANC-1 cells; it therefore appears to be a so-called motility factor. Only TGF-beta1 and IL-6 were recognized in the SW-C.M. among cytokines thought to stimulate cell motility. These cytokines stimulated the motility of PANC-1 cells, but differed from PDMF in the neutralizing test with antibody against these cytokines. Results of characterization and preliminary purification suggest that this factor may be a novel motility factor. The above findings suggest that this motility factor may play an important role in the invasion and metastasis of pancreatic cancer, and complete purification of it will be useful in elucidating the mechanism of progression of cancer and designing a strategy for inhibition of invasion and metastasis of pancreatic cancer.
Clin Exp Metastasis 1997 May
PMID:Identification and characterization of motility stimulating factor secreted from pancreatic cancer cells: role in tumor invasion and metastasis. 917 30

Despite its well documented unfavourable prognostic significance in several human diseases, including cancer, the cytokinic mechanisms responsible for an increased erythrosedimentation rate (ESR) still remain to be better analyzed and defined. The recent possibility to measure cytokine concentrations in the blood of patients has allowed us to explore the possible relation between ESR values and endogenous cytokine secretions. This preliminary study was performed to evaluate the relationship between ESR values and serum levels of IL-2 and IL-6, which represent the most important cytokines responsible for the activation and the suppression, respectively, of host anticancer immune reaction. The study included 33 consecutive solid tumor patients, 22 of whom showed distant organ metastases. Abnormally high values of ESR were present in 21 patients, including 18/22 metastatic patients and 3/11 nonmetastatic patients. Patients with elevated values of ESR showed significantly higher mean levels of IL-6 and significantly lower mean concentrations of IL-2 with respect to those found in patients with normal ESR values. These results would show that cancer-related increase in ESR values is associated with low levels of IL-2 and high levels of IL-6. Since IL-2 plays an essential role in the anticancer immunity and IL-6 may suppress the antitumor immune defenses, the evidence of low levels of IL-2 and high values of IL-6 in cancer patients with increased ESR values would explain the unfavourable prognostic significance of high ESR values in human neoplasms.
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PMID:Clinical significance of erythrosedimentation rate in cancer in relation to cytokine production: correlation with high IL-6 and low IL-2 blood concentrations. 925 Aug 87

Blood levels of the immunosuppressive cytokines IL-6 and IL-10 are often abnormally high in patients with advanced cancer. However, since IL-6 and IL-10 may be produced by macrophages and TH2 cells, the evidence of abnormally high values of IL-6 and/or IL-10 may reflect hyperactivation either of the macrophage system or of TH2 cell functions. In contrast, IL-4 is almost completely produced by the TH2 lymphocytes. Therefore, evaluation of IL-4 levels could help to differentiate macrophage from TH2 cell hyperactivation. This study was performed to investigate IL-4 serum levels in a group of cancer patients in relation to the stage of disease and to the secretion of other cytokines. The study included 50 patients, 28 of whom showed distant organ metastases. Lung cancer and gastrointestinal cancers were the most frequent neoplasms in our patients. The control group consisted of 60 healthy subjects. IL-4 was measured by the Elisa method. No patient showed high levels of IL-4. No significant differences were seen between controls and cancer patients, nor between metastatic and non-metastatic patients. In addition, no significant differences in IL-4 mean values were found between patients with normal or high levels of IL-6 and IL-10, or between patients with normal or low IL-2 concentrations. This preliminary study seems to exclude cancer-related abnormally high secretion of IL-4. Therefore, the high levels of IL-6 and/or IL-10 often occurring in advanced neoplastic disease would mainly depend on macrophage production.
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PMID:Interleukin-4 blood concentrations in early and metastatic human solid neoplasms. 934 36

The occurrence of breast cancer metastases is preferential to certain organs. Astrocytes may play an important role in the development of brain metastases, as these cells have been shown to respond to extracellular stimuli by producing many cytokines and growth factors that can modulate tumor cell proliferation, growth, and/or metastases. To test this hypothesis, we analyzed the responses of the human breast cancer cell line MDA-MB-435 and its metastatic sublines to astrocyte primary cultures from newborn rat cerebra. Astrocyte purity of the glial cell cultures was demonstrated by glial fibrillary acidic protein and rat neural antigen-2 (Ran-2) immunopositive staining. The 435-Br1 cell line, which was derived from a brain metastases in a nude mouse, showed increased adhesion to astrocytes and enhanced growth in vitro in the presence of media from Con A-stimulated astrocytes, relative to the parental MDA-MB-435 and the lung metastasis-derived variant 435-Lung2. Furthermore, the growth-stimulatory effect was partially reversed by anti-IL-6, anti-transforming growth factor beta (anti-TGF beta), and anti-IGF-I antibodies, indicating that these metastatic cells use exogenous cytokines as paracrine growth factors. In an attempt to elucidate the role of several biologic-response modifiers produced by astrocytes, we tested the responses of MDA-MB-435 cells to purified cytokines and growth factors. We found that the addition of recombinant human or mouse IL-6 produced a variety of responses in the different 435 metastatic variants. Furthermore, IL-6 receptor (IL-6R) expression was slightly increased in the 435-Br1 cells, and exogenous IL-6 rescued 435-Br1 cells from apoptosis in serum-depleted cultures. No apoptotic protective effect was observed in either MDA-MB-435 parental cells or 435-Lung2 cells. Thus, responses to exogenous IL-6 might determine the differences among these metastatic variants by extending cell survival of selected subpopulations, giving them the opportunity to respond to growth factors or other favorable conditions that might be present. These results suggest that cytokines produced by glial cells in vivo may contribute, in a paracrine manner, to the development of brain metastases by breast cancer cells.
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PMID:Astrocyte-derived cytokines contribute to the metastatic brain specificity of breast cancer cells. 935 70

Metastasis of pancreas carcinoma to the liver via the portal vein carries the gravest prognosis to patients. Using 10 cultured lines of pancreas carcinoma (PCI), established in our laboratory, we examined phenotypes that are important in hematogenous metastasis to the liver in anti-asialo GM1 treated nude mice. IL-6 production by PCI lines inversely correlated with liver metastasis, indicating that tumor-derived IL-6 may modulate metastatic competence. Therefore, we transfected human interleukin-6 cDNA in combination with the cytomegalovirus promoter to the non-IL-6 producer PCI-43, the line with the highest metastatic potential. Thus we established interleukin-6 high-, low-, and non-producer PCI-43, variant lines. Transfection itself did not endow PCI-43 line with alterations in surface phenotypes, kinesis, invasiveness, and doubling time in vitro. Metastatic potential of PCI-43 was profoundly suppressed in IL-6 high producer sublines. In mice inoculated with IL-6 high-producer PCI-43, an increase in human IL-6 in sera, as well as an appearance of PCI-43-reactive IgG was seen. The reduction in metastasis, therefore, may be mediated by antibody-dependent or complement-dependent cytotoxicity.
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PMID:[The effect of IL-6 produced by pancreatic carcinoma cells on blood-borne metastasis to the liver: a study on in vivo nude mouse model]. 937 58

The presence of mRNA transcripts for cytokines in normal and neoplastic human breast tissue has been investigated. Using reverse transcriptase-linked polymerase chain reaction (RT-PCR), we have specifically screened for the following cytokines: interleukin (IL)-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, tumour necrosis factor (TNF)-alpha, TNF-beta and interferon (IFN)-gamma. No significant differences in expression of IL-1alpha, IL-1beta, IL-4, IL-6, TNF-alpha or TNF-beta were observed between the 2 groups of tissues. However, there was a significant difference in expression of IL-8 transcripts (p = 0.0017) which was higher in the neoplastic population. Transcripts for IL-2, IL-3, IL-5, IL-7 and IFN-gamma were not detected in either group. There was no evidence of associations between cytokine expression and tumour histological grade, patient age or lymph node metastases. Correlating tumour types with specific cytokine transcripts revealed high expression of IL-8, and to a lesser extent, IL-8 and TNF-beta irrespective of tumour origin. Analysis of primary epithelial and stromal cultures derived from both types of tissue showed that increased levels of IL-8, but not IL-6, were secreted by cells obtained from tumours. Thus, breast tissue of both normal and neoplastic origin expresses a wide range of cytokines. Increased or aberrant expression of cytokines, in particular IL-8, may be involved in the development/progression of breast cancer.
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PMID:Expression of cytokine messenger RNA in normal and neoplastic human breast tissue: identification of interleukin-8 as a potential regulatory factor in breast tumours. 937 54

Interleukin-2 (IL-2) and interleukin-12 (IL-12) may represent the most important antitumour cytokines in human neoplasms. IL-2 blood levels decrease in advanced solid malignancies, but currently there are no data on IL-12 secretion in cancer patients. This study was performed to obtain preliminary data about IL-12 secretion in patients with solid malignant tumours, either in relation to the extension of disease, or to other cytokines, including IL-2, IL-6 and IL-10. The study included 40 solid cancer patients, 24 of whom showed distant organ metastases. Cytokine serum levels were measured by an enzyme immunoassay of blood samples collected during the morning. No patient had abnormally low levels of IL-12, but the levels were high in 14/14 (35%) patients. Mean levels of IL-12 were significantly higher in metastatic patients compared with non-metastatic patients (P < 0.05). Moreover, metastatic patients with high blood concentrations of IL-12 showed significantly lower levels of IL-10 than metastatic patients with normal IL-12 values, while no difference was seen in IL-2 mean concentrations. IL-6 mean levels were lower in metastatic patients with increased IL-12 levels, but this was non-significant. This preliminary study shows that advanced solid cancers are not characterised by a diminished secretion of IL-12, but rather IL-12 levels tend to be abnormally high in metastatic cancer patients.
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PMID:Interleukin-12 in early or advanced cancer patients. 938 37

In a recent phase I study of inhalative, human natural interleukin-2 (hnIL-2) treatment of pulmonary metastases from previously resected solid tumors (mainly renal carcinoma), we have reported that this treatment resulted in an increased accessory function of alveolar macrophages (AM) [1]. Encouraged by these data, we investigated the influence of hnIL-2 inhalation on proinflammatory cytokines spontaneously released by AM. Bronchoalveolar lavage was performed in four groups, each of four patients, before and after 2 weeks of daily inhalation of 0, 200,000, 600,000 and 1,200,000 IU of hnIL-2, respectively. Bronchoalveolar cells were cultured without stimulation to allow spontaneous release over a period of 24 h, into the supernatant. Concentrations of tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8 and macrophage inflammatory protein-1alpha (MIP-1alpha) were determined by the ELISA technique. Before hnIL-2 inhalation, we measured the following spontaneous cytokine release: TNF-alpha: 1,115.4 +/- 469.1 pg/ml, IL-6: 267.5 +/- 67.7 pg/ml cells, IL-8: 137.8 +/- 40.5 ng/ml, MIP-1alpha: 9.5 +/- 6.8 ng/ml. Inhalation of hnIL-2 did not result in any significant changes in these cytokines. Comparing TNF-alpha release in healthy controls (250.6 +/- 46.7 pg/ml) with that of tumor patients (1,115.4 +/- 469.1 pg/ml), we observed significantly (p < 0.05) elevated TNF-alpha levels in the patient group, which did not change significantly in response to IL-2 inhalation. Our data demonstrate that the activation of AM previously observed after hnIL-2 inhalation is not directly related to a hnIL-2-induced cytokine release by bronchoalveolar cells.
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PMID:Spontaneous and interleukin-2-modulated cytokine release by bronchoalveolar cells in pulmonary malignancy. 945 20


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