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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcoma is the most common primary malignant bone tumor. The peak incidence is in adolescence and the prognosis is very poor. Even after amputation and chemotherapy, many patients who suffer from osteosarcoma die of lung metastases within 2 years. This report documents a study of the in vitro antitumor activity of cytokines against three human osteosarcoma cell lines. The cell lines MG-63, SAOS-2, and TE-85 were incubated with TNF-alpha, IL-1, or IFN-gamma alone or in combination. TNF-alpha, IL-1, and IFN-gamma had antiproliferative activity against all three cell lines. TNF-alpha and IFN-gamma were the most effective against SAOS-2; MG-63 cells were the most sensitive to IL-1, and TE-85 cells were resistant to TNF-alpha and IL-1 but sensitive to IFN-gamma. The synergistic antitumor effect of TNF-alpha plus IFN-gamma, IL-1 alpha, or IL-1 beta or of IFN-gamma plus IL-1 alpha or IL-1 beta was higher than that obtained when the cytokines were employed alone.
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PMID:Antitumor activity of TNF-alpha, IL-1, and IFN-gamma against three human osteosarcoma cell lines. 193 72

We have examined the ability of peripheral blood monocytes (PBMs) isolated from AIDS-related Kaposi's sarcoma (KS) patients or normal donors to kill (a) autologous KS tumor cells from skin biopsies of AIDS patients, (b) a tumorigenic cell line derived from a histologically verified AIDS-KS skin tumor, and (c) the WEHI-164 fibrosarcoma line. Unstimulated PBMs, and PBMs activated by IFNs, IL-2, or TNF-alpha, were tested for their ability to lyse 51Cr-labeled tumor targets. PBMs from both normal and KS patients, when activated by cytokines, showed enhanced cytolysis of both WEHI-164 and the KS cell line. PBMs from two of three AIDS patients lysed their autologous fresh KS tumor cells. These results indicate that PBMs from AIDS-KS patients can be induced by cytokines to elicit potent antitumor activity, including cytolysis of autologous KS tumor cells.
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PMID:Cytokine-activated human monocytes show differential cytotoxicity toward fresh and cultured Kaposi's sarcoma cells. 194 30

We have studied the effects of high-energy shock waves (HESW) alone or in combination with biological response modifiers on the growth of five human kidney cancer xenografts in mice. Exposure of the tumors to three sessions of 800 shock waves every 48 hours with 18.4 kV, 37.5 MPa, on the commercially available Lithostar resulted in a temporary growth delay. The sensitivity for HESW was related to the doubling time of the tumor. Several days after stopping the HESW administration, the tumors regained their original growth potential with the same doubling time. The systemic application of Tumor Necrosis Factor-alpha (TNF-alpha, 500 ng/g body weight, 5 times/week) and/or Interferon-alpha (IFN-alpha, 5.0 ng/g body weight, 3 times/week) subcutaneously around the tumor also had a limited effect on the growth of these established tumors (60-80 mm3). The combination of HESW with TNF-alpha and IFN-alpha resulted in an almost complete cessation of tumor growth in the NU-1 human kidney xenograft and had an additive antitumor effect in the NU-3. Synergism was also seen in the NU-1 and NU-3 with the combination of HESW and TNF-alpha, while the combination with IFN-alpha had only a limited effect on tumor growth. So TNF-alpha was the active agent, that enhanced the antiproliferative effects of shock waves. In the NC-65 tumor (same doubling time as the NU-1 and NU-3, but less well vascularized), the antiproliferative effect of HESW was not potentiated by TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of high-energy shock waves combined with biological response modifiers in different human kidney cancer xenografts. 194 50

Tumorigenesis and invasive capacity of tumor cells are affected by the interactions between the tumor cells and the host cells; in particular, they are regulated by growth factors released from host cells. We have studied the effect of growth factors and cytokine on tumorigenesis and invasive capacity of tumor cells by examining a regressor tumor cell line (ER-1) derived from SHR rat mammary adenocarcinoma. The regressor tumor cells grew progressively in immunosuppressed rats, but spontaneously regressed in normal rats. We studied in vitro effect of growth factors on invasive capacity of ER-1 tumor cells into mesothelial cells obtained from SHR rats. As the results, pretreatment with EGF or TGF-beta significantly enhanced invasive capacity of ER-1 cells, whereas TNF-alpha did not show any effect. We pretreated ER-1 cells with EGF or TGF-beta for 24 hours in vitro, and then intraperitoneally transplanted them into SHR rats. The treated regressor tumor cells grew and killed the host. These results suggest that tumorigenesis and invasive capacity of regressor tumor cells are mediated by growth factors which promote growth and invasive abilities of tumor cells.
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PMID:[Enhancement of tumorigenesis and invasive capacity of regressor tumor cell by growth factors]. 195 44

We have investigated the ability of metastatic cells to produce the macrophage cytokine, TNF-alpha/cachectin, as these cells have macrophage-like properties such as infiltration and migration. We looked for TNF-alpha/cachectin in three tumor cell lines derived from human malignant melanomas and six co-cultivated malignant melanomas derived, in vitro, from these three cell lines plus angioma fibroblasts. Immunohistochemistry with an anti-TNF-alpha/cachectin monoclonal antibody showed that TNF-alpha/cachectin was produced by two of the three parent melanoma cell lines. All the tumor cells in both the co-cultivated malignant melanomas and their in vitro tumorous nodules produced TNF-alpha/cachectin, even those derived from the melanoma cell line, which originally did not. The results clearly show that TNF-alpha/cachectin can be produced by non-hematopoietic tumor cells. A co-cultivated tumor model prepared from other types of human tumor cell lines promises to provide a useful tool for exploring the relationship between TNF-alpha/cachectin and oncogenesis.
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PMID:Immunolocation of TNF-alpha/cachectin in human melanoma cells: studies on co-cultivated malignant melanoma. 199 83

Studies of the anti-tumor activity of TNF-alpha in vivo have been hampered by the need to administer systemically toxic doses of the cytokine to obtain a curative response. To facilitate studies of the effect of high local concentrations of TNF-alpha on tumor growth and host immunity, a newly induced murine sarcoma was transduced with the gene for human TNF-alpha and the biologic characteristics of these cells were examined. We identified high and low TNF-producing tumor clones which exhibited stable TNF secretion over time. Significant amounts of membrane associated TNF were found in a high-TNF producing clone as well. No difference in the in vitro growth rates between TNF-producing and nonproducing cell lines was observed. In contrast, in vivo studies demonstrate that although unmodified parental tumor cells grew progressively when implanted s.c. in animals, tumor cells transduced with the TNF gene were found to regress in a significant number of animals after an initial phase of growth. This effect correlated with the amount of TNF produced and could be blocked with a specific anti-TNF antibody. Regressions of TNF-producing cells occurred in the absence of any demonstrable toxicity in the animals bearing these tumors. TNF-producing tumor cells could function in a paracrine fashion by inhibiting the growth of unmodified, parental tumor cells implanted at the same site. The ability of tumor cells to regress was abrogated by in vivo depletion of CD4+ or CD8+ T cell subsets and animals that had experienced regression of TNF-producing tumors rejected subsequent challenges of parental tumor. Our studies thus show that tumor cells elaborating high local concentrations of TNF regress in the absence of toxicity in the host and that this process requires the existence of intact host immunity. Studies of the lymphocytes infiltrating the gene modified tumors and attempts to use TNF gene modified tumor infiltrating lymphocytes to deliver high local concentrations of TNF to the tumor site without inducing systemic toxicity are underway.
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PMID:Murine tumor cells transduced with the gene for tumor necrosis factor-alpha. Evidence for paracrine immune effects of tumor necrosis factor against tumors. 201 45

Experimentally, TNF-alpha can mediate the hemorrhagic necrosis of certain tumors. Furthermore, evidence indicates that natural cytotoxic (NC) activity, a cell-mediated cytolytic activity that utilizes TNF-alpha in the lysis of target cells, is involved in preventing the outgrowth of certain NC/TNF-alpha-sensitive tumor cells. These observations raise the issue of whether soluble TNF-alpha normally serves as a tumor surveillance mechanism preventing the outgrowth of some tumors. To address this issue, we have used TNF-alpha to select TNF-alpha-resistant variants from the NC/TNF-alpha-sensitive mouse fibroblast cell line 10ME. Previously, we have demonstrated that 10ME is tumorigenic in immune-deficient mice but fails to form tumors in normal mice. Moreover, selection of NC-resistant variants from 10ME selects for both TNF-alpha resistance and tumorigenicity in normal mice. As cells that have been selected for NC resistance form tumors in normal mice, whereas the NC-sensitive parental cell line does not, it seems that escape from NC activity is sufficient to significantly increase the tumorigenic potential of the cell line. We show that the selection with TNF-alpha, although associated with NC resistance, does not increase the tumorigenic potential of 10ME cells but reduces it. Thus, NC activity appears to function as a mechanism to prevent tumor formation, and escape from NC activity allows for tumor formation; TNF-alpha does not have similar activity. Moreover, this suggests that NC activity is not equivalent to soluble TNF-alpha activity, but utilizes TNF-alpha more efficiently than soluble TNF-alpha, or NC activity involves both TNF-alpha and other effector mechanisms.
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PMID:In vitro selection of a cell line for resistance to lysis by tumor necrosis factor-alpha selects for reduced tumorigenicity. 202 74

The protein-bound polysaccharide extracted from a fungus, PSK, has been used as a biological response modifier in the treatment of cancer patients in Japan for over ten years. Although the antitumor mechanism of PSK is not fully understood, host-mediated antitumor activity has been claimed to play a significant role. The administration of PSK to tumor-bearing rodents inhibited tumor growth and modulated immune responses. To clarify the potential immunomodulating activities of PSK, we examined the direct effect of PSK on cytokine gene expression and production in human peripheral blood mononuclear cells (PBMC) in vitro. As determined by Northern blotting, PSK was a potent inducer of gene expression for IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor (TNF-alpha) and monocyte chemotactic and activating factor (MCAF), but not for IL-2 and lymphotoxin (LT). Expression of mRNA occurred at 1-3 hr in a dose dependent manner using from 5-400 micrograms/ml of PSK. Furthermore, these cytokines were also produced in response to PSK as detected by ELISA, RIA or bioassays. We speculate that these cytokines may mediate immunoenhancing actions of PSK in vivo.
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PMID:Induction of gene expression and production of immunomodulating cytokines by PSK in human peripheral blood mononuclear cells. 209 Aug 74

In a phase II study, the efficacy and toxicity of human recombinant tumor necrosis factor (rh TNF-alpha) were evaluated in patients with advanced colorectal carcinoma. Rh TNF-alpha was given as short term infusion at a dose of 3 x 10(5) U/m2 on three successive days. Treatment was repeated after a two week interval. The response was evaluated after four treatment cycles. In 15 patients entering the study, we found one partial response, one stable disease, 9 progressive diseases, and four patients who were not evaluable for tumor remission. There were numerous side effects of the treatment, mainly fever, chills, loss of appetite, leukopenia, and hepatotoxicity. In this regimen, rh TNF-alpha does not suggest a therapeutic advantage for treatment of advanced colorectal carcinoma.
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PMID:Tumor necrosis factor in advanced colorectal cancer: a phase II study. A trial of the phase I/II study group of the Association for Medical Oncology of the German Cancer Society. 209 81

We have previously reported that IL-3, a cytokine produced by both Th1 and Th2 type CD4+ T cells, displays macrophage-activating potential. IL-3, like IFN-gamma, readily induced functions related to Ag presentation (e.g., Ia and lymphocyte function-associated Ag-1 expression). However, in contrast to the response elicited by IFN-gamma, tumor cytotoxicity was not induced by IL-3. In this paper we have evaluated the capacity of IL-3 to regulate IL-1 expression. Our data demonstrate that although IL-3 alone was unable to induce the production of substantial IL-1 bioactivity in peritoneal exudate cells, it contributed synergistically to the induction of IL-1 bioactivity in the presence of suboptimal doses of LPS. It was of interest that IFN-gamma, which can also interact synergistically with LPS, was unable to complement the partial signals provided by IL-3 for the expression of IL-1 bioactivity, suggesting that IL-3 and IFN-gamma may be providing similar stimulatory signals in this respect. Our studies on the mechanism of synergy between IL-3 and LPS indicated that the effect of LPS did not appear to be mediated by the well-characterized LPS-inducible cytokines of macrophage origin (i.e., IL-1, alpha and beta, TNF-alpha, and IL-6). The best characterized function of IL-3 is its multicolony-stimulating activity as a CSF; in this context we also studied granulocyte-macrophage CSF and noted that it behaves similarly to IL-3 in that it can synergistically contribute to IL-1 induction. A similar, but more dramatic induction of IL-1 synthesis in response to IL-3 was demonstrated by the P388.D1 murine macrophage cell line. The kinetics and the molecular mechanism of the response of P388.D1 to IL-3 indicate several unique features of IL-3-induced IL-1 expression: 1) IL-3 itself induced IL-1 mRNA expression, which was unaccompanied by substantial production of bioactivity, either cell-associated or secreted into the culture supernatant; 2) IL-3 synergized with suboptimal doses of LPS to induce not only heightened IL-1 mRNA levels but bioactivity as well; and 3) IL-3, when combined with LPS, altered the kinetics of IL-1 message and bioactive protein production in response to LPS: IL-3 and LPS induced an early release (3 to 7 h poststimulation) of the IL-1 protein as well as a second peak of mRNA and bioactivity (at 12 to 36 h), which was not observed in response to either IL-3 or LPS alone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of macrophage activation by IL-3. II. IL-3 and lipopolysaccharide act synergistically in the regulation of IL-1 expression. 210 77


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