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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 795 (1996), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Immunological reviews 174 (2000), S. 0 
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Protective cell-mediated immune responses in cancer are critically dependent on T-helper type 1 (TH1) cytokines such as interferon-γ (IFN-γ). We have previously shown that the combination of CD40 stimulation and interleukin-2 (IL-2) leads to synergistic antitumor responses in several ...
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of these studies was to determine whether stimulated human lymphocytes produce lymphokines distinct from IFNγ, that can activate human blood monocytes to lyse tumor cells. We undertook this investigation because of the controversy concerning whether MAF and IFNγ are the same molecule. Crude lymphokine preparations prepared from normal human mononuclear cells incubated with Con A and rich in MAF activity also contained 1000 U/ml IFNγ as measured by the virus neutralization assay. However, the induction of tumoridical activity in monocytes by the lymphokine preparation could be dissociated from the IFNγ activity, based on the following data: (1) Heat treatment (100 °C for 2 min) removed the antiviral activity of the lymphokine yet did not diminish its MAF-like activity when measured in a 72 h cytotoxicity assay against 125I IUdR-labeled human A375 melanoma cells. (2) Likewise, treatment of this lymphokine preparation with a twofold excess of anti-IFNγ antibody neutralized antiviral activity but once again had no effect on its ability to activate monocyte tumoricidal function. In contrast, both heat treatment and anti-IFNγ antibody abolished monocyte activation by equivalent units of human recombinant IFNγ. Taken together, these data suggest that there is a molecule(s) distinct from IFNγ which can activate human monocytes for tumoricidal function. Furthermore, this dissociation of MAF and IFNγ activity was dependent on the use of a long-term (72 h) assay, since activation of tumoricidal activity in an 18–24 h assay appeared to be attributable solely to IFNγ.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0843
    Keywords: Key words Antitumor activity ; Cytokine ; Interleukin 12 ; Interleukin 2 ; Interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Interleukin 12 (IL-12) is a heterodimeric cytokine with a number of biological effects that are consistent with its potential role as an antitumor agent. The antimetastatic and antitumor activities of IL-12 have been demonstrated in a number of murine tumor models. Both the inhibition of established experimental pulmonary or hepatic metastases and a reduction in spontaneous metastases have been achieved by treatment with murine IL-12. Systemic treatment of mice bearing subcutaneous tumors with IL-12 results in tumor growth inhibition, prolongation of survival, and, in some models, tumor regression. The antitumor effect of IL-12 in these models is dose-dependent and can be initiated against well-established tumors. Mice cured of their tumor by IL-12 treatment are specifically immune to rechallenge with the same tumor. A series of experiments have demonstrated that both T-cells and interferon-gamma (IFN-γ) induction are necessary for the optimal antitumor effects of IL-12. However, the antitumor efficacy of IL-12 has not been observed after exogenous administration of murine IFN-γ, suggesting that additional factors may be important for the antitumor effects of IL-12. In several tumor models, IL-12 is more active or has a larger therapeutic window than either IL-2 or IFN-α, two cytokines with demonstrated antitumor activity against human malignancies. Combining IL-12 with other cytokines or chemotherapeutic drugs can improve antitumor effects.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Cancer immunology immunotherapy 27 (1988), S. 109-113 
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Murine bone marrow cells immortalized in vitro by the J2 recombinant retrovirus bearing the v-raf and v-myc oncogenes have the functional and phenotypic characteristics of macrophages. The present study was designed to determine whether these cells are tumorigenic in athymic or euthymic mice. One cloned cell line (GG2EE), that had been previously derived and characterized was used for this purpose. The results demonstrated that GG2EE cells were tumorigenic in allogeneic athymic BALB/c mice at doses of 1×104 to 1×107 cells per mouse regardless of the route administration. All mice utlimately died of progressive tumor growth. Conversely, the GG2EE cells were nontumorigenic or transiently tumorigenic in syngeneic euthymic C3H/HeJ mice. Further studies in BALB/c athymic mice demonstrated that the GG2EE cells were directly tumorigenic since ascites tumors (GG2EE-V) that developed expressed the H-2k surface phenotype of the injected GG2EE cells, excluding the possibility that the J2 virus constitutively produced by GG2EE cells caused in vivo transformation and therefore tumors of host cell origin. The in vivo passaged cells continued to express the M1/69, MAC-1, MAC-2, F4/80, Fc receptor and Ly5.1 antigens characterically expressed on the parental line. Biological properties including interferon-γ-induced Ia expression, phagocytosis, and activation for cytotoxicity were also retained following in vivo passage. These results demonstrated that J2 virus-immortalized GG2EE cells were directly tumorigenic in athymic mice in vivo and that the macrophage phenotype was maintained in these neoplastic cells. These observations suggest that this tumor model may be valuable for the study of macrophage function as well as therapeutic approaches to oncogen-expressing retrovirus-induced tumors.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied the formation of experimental B16 melanoma metastases in the lungs of mice inoculated IV with tumoricidal or nontumoricidal peritoneal macrophages elicited by various agents. IV inoculation of peritoneal Mϕ elicited by Brewer's thioglycollate medium (TG-Mϕ) 1 day before the injection of B16 melanoma cells dramatically increased the number of metastatic foci in the lungs. NIH thioglycollate broth and proteose peptone each elicited a relatively low number of Mϕ, which were morphologically distinguishable from TG-Mϕ and did not influence the yield of B16 melanoma colonies in the lungs. Resident or C. pravum-elicited Mϕ also did not augment metastatis formation. TG-Mϕ became highly tumoricidal after IP stimulation with poly I: C. However, tumoricidal TG-Mϕ inoculated IV 1 day before IV inoculation of B16 melanoma cells did not have an antimetastatic effect. On the contrary, both tumoricidal and nontumoricidal TG-Mϕ augmented metastasis formation. Poly I: C treatment had a substantial antimetastatic effect in the normal mice, but not in mice with adoptively transferred TG-Mϕ. Histological analysis revealed that IV-inoculated TG-Mϕ (tumoricidal or nontumoricidal, either viable or disrupted) induced severe intravascular reaction in the lungs, but not in the liver or kidney. This reaction manifested in the aggregation of the various blood cells, preferentially neutrophils. These reactions were not observed after IV inoculation of PMϕ or NIH TG-Mϕ. Intravascular inflammatory reactions induced by TG-Mϕ may be responsible for the augmentation of metastasis formation, partly by suppression of NK reactivity and mostly by the acceleration of the processes of tumor cell extravasation. These data may provide some insight into the failure to achieve systemic adoptive immunotherapy using activated peritoneal TG-Mϕ.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Administration of several biological response modifiers (BRMs) to mice strongly augmented natural killer (NK) activity of leukocytes isolated from the liver. This augmentation of NK activity was induced by two synthetic molecules (MVE-2 and poly ICLC), by two BRMs of bacterial origin (formalin-fixed Propionibacterium acnes: P. acnes and a streptococcal cell wall preparation designated OK-432), as well as a single injection of human recombinant interleukin-2 (hrIL 2). All of these BRMs augmented NK activity in the liver to a greater degree than in the spleen. In addition, adherent leukocytes (〉90% macrophages) isolated from the liver following P. acnes administration also exhibited augmented macrophage-mediated cytotoxicity. This cytotoxicity was characterized as macrophage mediated and distinguished from NK activity, on the basis of adherence purification, kinetics of cytotoxicity, and target cell selectivity. The results demonstrate that a variety of BRMs induce augmented natural immunity in the liver and suggest that such organ-associated immune responses may play an important role in the antimetastatic effects of BRMs.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have used a transplantable murine adenocarcinoma of renal origin (Renca) introduced to the abdomen by i. p. injection of a tumor cell suspension, to study the therapeutic potential of adoptive immunotherapy and/or biological response modifiers (BRMs). This tumor model is therapeutically challenging since the tumor grows progressively resulting in extensive peritoneal carcinomatosis, with hemorrhagic ascites, metastases to abdominal lymph nodes, liver, most serous membranes, spleen, and in some animals, pulmonary metastases. Without therapy, death occurs invariably in 36±3 days. In vitro, the tumor is lysed by lymphocytes obtained from the peritoneal cavity of mice treated with human recombinant interleukin-2 (rIL-2) and by cototoxic lymphocytes stimulated by in vitro culture with human rIL-2. Treatment of i. p. Renca with a single i. p. injection of the chemotherapeutic agent doxorubicin hydrochloride (DOX), or adoptive transfer of in vitro stimulated cytotoxic lymphocytes together with rIL-2 cured 50% and 20% of the tumor-bearing mice, respectively. In contrast, combined therapy with DOX and adoptive transfer of in vitro stimulated cytotoxic lymphocytes and rIL-2 cured the majority (90%) of tumor-bearing mice. These results suggest that administration of immunotherapy with in vitro activated cytotoxic cells together with human rIL-2 substantially enhances the effectiveness of chemotherapy.
    Type of Medium: Electronic Resource
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