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  • 1
    Electronic Resource
    Electronic Resource
    Radiotherapy for genes that cause cancer (1995)
    [s.l.] : Nature Publishing Group
    Nature medicine 1 (1995), S. 1215-1217 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Conventional radiotherapy for cancer achieves a therapeutic advantage by exploiting differences between tumour and normal tissue with respect to repair, cell-cycle redistribution, repopulation, and reoxygenation, and by limiting the dose received by critical normal tissues. The probability of ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nm1195-1215
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  • 2
    Electronic Resource
    Electronic Resource
    Cytokine-mediated gene therapy for cancer (1994)
    Springer
    Annals of surgical oncology 1 (1994), S. 436-450 
    Details
    ISSN: 1534-4681
    Keywords: Cytokine ; Gene transfer ; Tumor rejection ; Protective immunity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Significant interest has been generated in the gene therapy of cancer. One strategy involves tumor-directed cytokine gene transfer and its effects on tumor immunobiology. Methods: The authors review the current literature pertaining to cytokine gene therapy of cancer and provide a description of gene transfer methods currently being evaluated. Results: Several cytokine gene transfer models have been described involving at least 12 different cytokines. The introduction of cytokine genes into experimental animal tumors improves their ability to be recognized and destroyed by the host immune system. Certain cytokines will regulate phenotypic properties such as major histocompatibility complex antigens, immunosuppressive peptides, protooncogenes or endogenous cytokine production. Cytokine-transduced tumors attract an inflammatory exudate in vivo that generally results in tumor destruction. The nature of the infiltrate (lymphocytic, mononuclear, granulocytic) cannot always be predicted from the known biological properties of each cytokine. Untransduced bystander tumor cells are usually also destroyed. Some, but not all, cytokine transductions result in the generation of systemic major histocompatibility complex-restricted, tumor immunity. It has been hypothesized that the local continuous production of cytokines by tumor cells provides an optimal microenvironment for antigen recognition and the generation of T-cell immunity. Conclusions: These experimental observations hold promise for the clinical application of genetically engineered tumor vaccines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02303818
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  • 3
    Electronic Resource
    Electronic Resource
    Intratumoral interleukin-2 immunotherapy: Activation of tumor-infiltrating and splenic lymphocytes in vivo (1993)
    Springer
    Cancer immunology immunotherapy 36 (1993), S. 156-162 
    Details
    ISSN: 1432-0851
    Keywords: Interleukin-2 ; Immunotherapy ; Tumorinfiltrating lymphocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Direct intratumoral injection of interleukin-2 (IL-2) was evaluated in a murine model. Balb/c mice received 5 × 104 Line 1 alveolar carcinoma cells (L1C2) by subcutaneous injection. On the third day following tumor implantation, mice received injections of IL-2 (5 × 103−5 × 104 units) or diluent twice daily, either by i. p. or intratumoral injection, 5 days/week for 3 weeks. Intratumoral injection of 5 × 104 units IL-2 significantly reduced tumor volume (P 〈0.05 versus control), increased median survival time (P = 0.0001), and resulted in a 23.5% cure rate (P = 0.008). There were no long-term survivors in the other treatment groups. Both tumor-infiltrating lymphocytes (TIL) and splenic lymphocytes isolated directly from IL-2-treated mice demonstrated enhanced cytolytic activity compared to diluent-treated controls. To determine whether non-T-cell-mediated antitumor responses were active in our model, intratumoral immunotherapy was evaluated in athymic Balb/cnu/nu mice. In order to decrease the recruitment of lymphocyte precursors, nude mice were splenectomized and received cyclophosphamide prior to tumor injection and IL-2 therapy. Intratumoral IL-2 immunotherapy also significantly decreased tumor volume in these immunodeficient mice (P 〈0.02), but did not lead to long-term survival. We conclude that both TIL and splenic lymphocytes are activated in vivo in response to intratumoral IL-2 immunotherapy, suggesting that intratumoral therapy with IL-2 activates both local and systemic antitumor responses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01741086
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  • 4
    Electronic Resource
    Electronic Resource
    Inhibitory effect of locally produced and exogenous interleukin-6 on tumor growth in vivo (1994)
    Springer
    Cancer immunology immunotherapy 38 (1994), S. 339-345 
    Details
    ISSN: 1432-0851
    Keywords: Interleukin-6 ; Tumor-associated macrophages ; Gene therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to define the potential antitumor activity of the multifunctional cytokine interleukin-6 (IL-6), retrovirus-mediated gene transfer was used to introduce and express a cDNA encoding human IL-6 in the murine fibrosarcoma cell line Fsa-R. Although these genetically modified tumor cells appeared morphologically and phenotypically identical to control Fsa-R cells and had a similar plating efficiency in vitro, they were found to exhibit greatly reduced tumorigenicity in vivo following intravenous injection into syngeneic recipients. Exogenous IL-6 was shown to produce a similar inhibition of tumor growth in the lung if administered intraperitoneally. In contrast, tumor growth in subcutaneous sites was inhibited only if the tumor cells were engineered to express IL-6 locally, or if IL-6 was administered intratumorally. Intraperitoneal injection of IL-6 had no inhibitory effect. Tumors that did grow from IL-6-producing tumor cell inocula in subcutaneous sites were found to contain large numbers of macrophages. These results demonstrate that the antitumor activity of systemically administered IL-6 varies depending on the site of tumor growth and suggest an important role for IL-6 in the recruitment, proliferation and/or survival of tumor-associated macrophages.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01525513
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  • 5
    Electronic Resource
    Electronic Resource
    Immunoregulating activity of tumor-associated macrophages (1986)
    Springer
    Cancer immunology immunotherapy 23 (1986), S. 67-72 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this report, we examine the antigen nonspecific immunoregulating activity of macrophages isolated from the murine methylcholanthrene-induced fibrosarcoma FSA. These cells were shown to enhance the primary anti-CRBC PFC response of whole normal spleen cells in a dose-dependent fashion. This function was associated with a subpopulation of large Ia-negative macrophages and was mediated by a soluble macrophage-derived factor that appeared to act by stimulating the proliferation and/or differentiation of antigen-reactive T cells. The relationship of this factor to previously described monokines is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00205558
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  • 6
    Electronic Resource
    Electronic Resource
    Inhibitory effect of locally produced and exogenous interleukin-6 on tumor growth in vivo (1994)
    Springer
    Cancer immunology immunotherapy 38 (1994), S. 339-345 
    Details
    ISSN: 1432-0851
    Keywords: Key words: Interleukin-6 – Tumor-associated macrophages – Gene therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. In order to define the potential antitumor activity of the multifunctional cytokine interleukin-6 (IL-6), retrovirus-mediated gene transfer was used to introduce and express a cDNA encoding human IL-6 in the murine fibrosarcoma cell line Fsa-R. Although these genetically modified tumor cells appeared morphologically and phenotypically identical to control Fsa-R cells and had a similar plating efficiency in vitro, they were found to exhibit greatly reduced tumorigenicity in vivo following intravenous injection into syngeneic recipients. Exogenous IL-6 was shown to produce a similar inhibition of tumor growth in the lung if administered intraperitoneally. In contrast, tumor growth in subcutaneous sites was inhibited only if the tumor cells were engineered to express IL-6 locally, or if IL-6 was administered intratumorally. Intraperitoneal injection of IL-6 had no inhibitory effect. Tumors that did grow from IL-6-producing tumor cell inocula in subcutaneous sites were found to contain large numbers of macrophages. These results demonstrate that the antitumor activity of systemically administered IL-6 varies depending on the site of tumor growth and suggest an important role for IL-6 in the recruitment, proliferation and/or survival of tumor-associated macrophages.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01525513
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  • 7
    Electronic Resource
    Electronic Resource
    Role of macrophage-colony-stimulating factor in regulating the accumulation and phenotype of tumor-associated macrophages (1997)
    Springer
    Cancer immunology immunotherapy 44 (1997), S. 165-172 
    Details
    ISSN: 1432-0851
    Keywords: Key words Tumor-associated macrophages ; M-CSF ; op/op mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In order to better define the role played by tumor-cell-derived macrophage-colony-stimulating factor (M-CSF) in regulating the recruitment and phenotype of tumor-associated macrophages, Polyoma large T-transformed fibroblastoid cell lines, derived from M-CSF-deficient osteopetrotic op/op mice and their phenotypically normal op/+ littermate controls, were inoculated into SCID (severe combined immunodeficiency) recipients and both the proportion and phenotype of the macrophages present within the tumors generated were determined. The results obtained indicate that, although tumors derived from M-CSF-deficient and M-CSF-producing tumor cell inoculate contain a similar proportion of macrophages, the macrophages isolated from tumors lacking M-CSF appear morphologically less mature and express lower levels of interleukin 1β, tumor necrosis factor α and FcRγII mRNA. Taken together, these data suggest that, although M-CSF does not appear to play a critical role in determining the macrophage content of these tumors, it does play a role in modulating the phenotype, and potentially the functional activity of the macrophages present within the tumor microenvironment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002620050369
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  • 8
    Electronic Resource
    Electronic Resource
    Concomitant development of granulocytosis and enhancement of metastases formation in tumor-bearing mice (1984)
    Springer
    Clinical & experimental metastasis 2 (1984), S. 181-190 
    Details
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: The experiments reported here show concomitant development of granulocytosis and enhancement of metastasis formation in C3Hf/Kam mice bearing NFSA fibrosarcoma. Both phenomena developed at approximately 2 weeks after s.c. transplantation of tumor cells, at a time when the tumor was approximately 10 mm in diameter. The number of granulocytes in the blood doubled approximately every 3·5 days, reaching about 30 times control levels shortly before the death of the mice. The magnitude of the metastasis enhancement formation by i.v. injection of tumor cells was three to four times the control value. Mice bearing NFSA had a significant increase in the number of endogenous CFUs. Plasma from NFSA-bearing mice and medium from cultured NFSA cells stimulatedin vitro growth of granulocyte and macrophage colonies from normal bone marrow cell precursors, and induced granulocytosis upon i.v. injection into normal mice. This shows that NFSA tumor secretes factor(s) with potent granulopoietic activity. Injection of plasma from tumor-bearing animals followed by i.v. injection of NFSA cells did not lead to the enhancement of metastasis, implying that granulocytosis might be rather concomitant manifestation than a causative factor of the enhancement of metastasis formation. Importance of granulocytosis as a paraneoplastic manifestation during tumor growth is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00132924
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