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  • 1
    Electronic Resource
    Electronic Resource
    Role of NK cells in tumour growth and metastasis in beige mice (1980)
    [s.l.] : Nature Publishing Group
    Nature 284 (1980), S. 622-624 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] NK cells seem to be pre-T cells that do not require thymic maturation. This could account for their presence in athymic nude mice6. The level of NK cell activity is genetically controlled7, age-dependent8 and may be augmented by numerous agents, including infection with lymphocytic choriomeningitis ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/284622a0
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  • 2
    Electronic Resource
    Electronic Resource
    Immunomodulatory and therapeutic properties of FK-565 in mice (1989)
    Springer
    Cancer immunology immunotherapy 28 (1989), S. 93-100 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The heptanoyl tripeptide, FK-565 is a biological response modifier with potent therapeutic properties for the treatment of experimental and spontaneous metastases. Doses of FK-565 greater than 5 mg/kg are required for in vivo augmentation of natural killer cells, macrophages, and for therapeutic activity, presumably because FK-565 is a peptide small molecular mass which is rapidly degraded and excreted. Optimal therapeutic activity is observed at approximately 25–50 mg/kg FK-565, administered i.v. three times per week for 4 weeks. In addition to its therapeutic properties, which were consistently greater than the positive control at optimal doses, FK-565 had significant immunoaugmentary properties for natural killer cells, macrophages, and T cells both in vitro and in vivo, suggesting that its therapeutic activity is due to immune augmentation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199108
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  • 3
    Electronic Resource
    Electronic Resource
    Immunologic enhancement of experimental metastasis in the rat (1984)
    Springer
    Cancer immunology immunotherapy 17 (1984), S. 42-50 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using a series of immunologically cross-reactive metastatic tumor variants, we demonstrate that serum from animals bearing pulmonary tumor colonies possesses enhancing properties in the experimental metastasis (lung colony) assay. Enhancement is produced by chronic serum administration and promotes the growth of tumor cells arrested in the lungs which would not otherwise proliferate to form grossly detectable lung nodules. Tumor-bearer serum from animals with lung colonies derived from the most highly metastatic variant examined is shown to possess enhancing properties in both BD-IX(H-1d) and BD-IV(H-1d) rat strains, while tumor-bearer serum from animals with lung colonies derived from the less metastatic parent tumor cell line possesses enhancing properties in the BD-IX rat strain only. Removal of immunoglobulin from enhancing serum by affinity column chromatography simultaneously removes the enhancing factor(s), and enhancing activity correlates with the presence of increased levels of Clq-binding immune complexes in the serum. Serum levels of immune complexes are shown to be more elevated in serum from animals bearing lung colonies derived from the most highly metastatic variant. The enhancing moieties are shown to bind to concanavalin A, but not to staphylococcal protein A, and the active fraction elutes from concanavalin A-Sepharose with α-methyl-mannoside. Consideration of immunoprecipitation studies on whole and fractionated enhancing sera, along with studies on affinity purified isotype fractions reveals that the activity resides with antibodies of IgG2b subclass.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00205496
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of bestatin on myelopoietic stem cells in normal and cyclophosphamide-treated mice (1990)
    Springer
    Cancer immunology immunotherapy 32 (1990), S. 75-80 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of bestatin on hematopoietic parameters and bone marrow progenitor activity (colony-forming unit — granulocyte/macrophage: CFU-GM) was examined in normal and myelosuppressed C57BL/6 mice. CFU-GM frequency and absolute number were determined with a limiting dilution analysis of bone marrow cells in soft agar using recombinant murine colony-stimulating factor — granulocyte/macrophage. We report that bestatin increased splenic, bone marrow, and peripheral blood cellularity and the number of CFU-GM over a dose range from 2.5 mg/kg through 100 mg/kg following i.p., i.v., or oral administration. The greatest myeloid stimulation was observed following multiple injections of bestatin. Bestatin also increased the recovery from cyclophosphamide-induced myelodepression as measured by these parameters. The hematopoietic properties of bestatin following oral administration is of potential importance for clinical application.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01754202
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  • 5
    Electronic Resource
    Electronic Resource
    Antitumor response to recombinant murine interferon γ correlates with enhanced immune function of organ-associated, but not recirculating cytolytic T lymphocytes and macrophages (1993)
    Springer
    Cancer immunology immunotherapy 37 (1993), S. 299-306 
    Details
    ISSN: 1432-0851
    Keywords: Murine interferon γ ; Antitumor response ; Organ-associated CTL ; Macrophages ; Immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanism of therapeutic activity for recombinant murine interferon-γ(rMu IFNγ) in the treatment of metastatic disease was investigated by comparing effector cell augmentation with therapeutic activity in mice bearing experimental lung metastases (B16-BL6 melanoma). Effector cell functions in spleen, peripheral blood, and lung (the tumor-bearing organ) were tested after 1 week and 3 weeks of rMu IFNγ administration (i.v. three times per week). Natural killer (NK), lymphokine-activated killer (LAK), cytolytic T lymphocyte (CTL) activities against specific and nonspecific targets, and macrophage tumoristatic activity were measured. rMu IFNγ demonstrated immunomodulatory activity in most assays of immune function. The optimal therapeutic protocol of rMu IFNγ (2.5×106 U/kg, three times per week) prolonged survival and decreased the number of pulmonary metastatic foci. This therapeutic activity was correlated with specific CTL activity from pulmonary parenchymal mononuclear cells (PPMC), but not from spleen or blood. Macrophage tumoristatic activity in PPMC also correlated with therapeutic activity, but activity in alveolar macrophages did not. However, therapeutic activity did not correlate with NK or LAK activity at any site. These results demonstrate that the optimal therapeutic protocol is the same as the optimal immunomodulatory dose for pulmonary CTL and macrophage activities. Furthermore, while immunological monitoring may help to optimize treatment protocols, current monitoring procedures that use readily accessible sites, particularly peripheral blood, may not accurately predict the therapeutic efficacy of biological response modifiers in clinical trials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01518452
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  • 6
    Electronic Resource
    Electronic Resource
    Differential recovery of polymorphonuclear neutrophils, B and T cell subpopulations in the thymus, bone marrow, spleen and blood of mice following split-dose polychemotherapy (1994)
    Springer
    Cancer immunology immunotherapy 39 (1994), S. 59-67 
    Details
    ISSN: 1432-0851
    Keywords: Key words: Chemotherapy – CD4 – CD8 – Mitogen – Thymus – FACS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. In these studies, we examined the effect of a maximum-tolerated, split-dose chemotherapy protocol of cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea carmustine on neutrophil and lymphocyte subpopulations in the peripheral blood (PBL), thymus, bone marrow and spleen. It was found that this protocol of polychemotherapy, modeled after the induction protocol used with autologous bone marrow transplantation for breast cancer, suppressed both B and T cell populations and T cell function at times when the absolute neutrophil count had returned to normal or supernormal numbers. In the peripheral blood, 7 days following initiation of chemotherapy, there was a twofold increase in the percentage of granulocytes as compared to the level in control animals on the basis of a differential count. The polymorphonuclear neutrophil (PMN) frequency in the bone marrow was increased on day 14 and statistically identical to that in control mice on all other days analyzed. In contrast to the bone marrow cells and PBL on day 7, the frequency of PMN in the spleen and thymus was depressed. B cells (B220+) were depressed in the PBL, spleen and bone marrow and took 18 – 32 days to return to their normal frequency, while the frequency of B cells in the thymus was increased owing to a loss of immature T cells. The percentage of CD3+ cells in the thymus, spleen and bone marrow was significantly increased and required 10 – 18 days to return to normal levels, while the absolute number of CD3+ cells in the blood varied around the normal value. The ratio of CD4+ to CD8+ cells in all the organs studied varied only slightly owing to a similar reconstitution of CD4+ and CD8+ cells. In contrast to the phenotypic recovery of the CD3+, CD4+ and CD8+ cells, the ability of the splenic lymphocytes to respond to concanavalin-A was depressed and remained depressed, despite the phenotypic reconstitution of the T cell subsets, on the basis of both percentage and absolute cell number. These results show a selective T and B cell depression following multi-drug, split-dose chemotherapy in tissue and blood leukocyte populations and a chronic depression in T cell function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01517182
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  • 7
    Electronic Resource
    Electronic Resource
    Differential recovery of polymorphonuclear neutrophils, B and T cell subpopulations in the thymus, bone marrow, spleen and blood of mice following split-dose polychemotherapy (1994)
    Springer
    Cancer immunology immunotherapy 39 (1994), S. 59-67 
    Details
    ISSN: 1432-0851
    Keywords: Chemotherapy ; CD4 ; CD8 ; Mitogen ; Thymus ; FACS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In these studies, we examined the effect of a maximum-tolerated, split-dose chemotherapy protocol of cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea carmustine on neutrophil and lymphocyte subpopulations in the peripheral blood (PBL), thymus, bone marrow and spleen. It was found that this protocol of polychemotherapy, modeled after the induction protocol used with autologous bone marrow transplantation for breast cancer, suppressed both B and T cell populations and T cell function at times when the absolute neutrophil count had returned to normal or supernormal numbers. In the peripheral blood, 7 days following initiation of chemotherapy, there was a twofold increase in the percentage of granulocytes as compared to the level in control animals on the basis of a differential count. The polymorphonuclear neutrophil (PMN) frequency in the bone marrow was increased on day 14 and statistically identical to that in control mice on all other days analyzed. In contrast to the bone marrow cells and PBL on day 7, the frequency of PMN in the spleen and thymus was depressed. B cells (B220+) were depressed in the PBL, spleen and bone marrow and took 18–32 days to return to their normal frequency, while the frequency of B cells in the thymus was increased owing to a loss of immature T cells. The percentage of CD3+ cells in the thymus, spleen and bone marrow was significantly increased and required 10–18 days to return to normal levels, while the absolute number of CD3+ cells in the blood varied around the normal value. The ratio of CD4+ to CD8+ cells in all the organs studied varied only slightly owing to a similar reconstitution of CD4+ and CD8+ cells. In contrast to the phenotypic recovery of the CD3+, CD4+ and CD8+ cells, the ability of the splenic lymphocytes to respond to concanavalin-A was depressed and remained depressed, despite the phenotypic reconstitution of the T cell subsets, on the basis of both percentage and absolute cell number. These results show a selective T and B cell depression following multi-drug, split-dose chemotherapy in tissue and blood leukocyte populations and a chronic depression in T cell function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01517182
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    Paper (German National Licenses)
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of bestatin and oral activity for treatment of experimental metastases (1989)
    Springer
    Cancer immunology immunotherapy 28 (1989), S. 29-33 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bestatin is a low molecular weight aminopeptidase inhibitor originally isolated from culture filtrates of Streptomyces olivoreticuli. The serum pharmacokinetics in mice are dependent on route of administration, with a short t1/2 (1.69 min t1/2α and 12.8 min t1/2β), but a high initial serum level following i.v. administration. When administered via the i.p., s.c., i.m., or p.o. routes of administration, bestatin had serum t1/2βs of 8.56, 16.91, 19.25, or 15.4 min, respectively. The maximum area under the curve (concentration×time) occurred following i.v. and i.m. administration, with a lower level following p.o. or i.p. administration. Bestatin had therapeutic activity for experimental metastases, not only following i.v., i.p., and i.m. routes of administration but also following oral administration. Because of its brief serum t1/2, bestatin's therapeutic activity depends on aggressive (either daily or twice daily injection, especially following p.o. administration) and high-dose administration. Thus, the rate-limiting aspect of bestatin's therapeutic activity appears to be associated with its pharmacokinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00205797
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  • 9
    Electronic Resource
    Electronic Resource
    Immunoselection of tumor variants resistant to antibody-mediated cytotoxicity (1982)
    Springer
    Cancer immunology immunotherapy 14 (1982), S. 124-131 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The immunological characteristics of two series of metastatic variants of restricted genetic origin were related to their lung-colony-forming potential. A series of metastatic variants was isolated from a tumor-cell population in which heterogeneity appeared following short-term in vivo passage, while a second series of variants were immunoselected in vitro for resistance to antibody-complement-mediated cell lysis. In the case of the first series, the sensitivity of the individual variants to cell-mediated and antibody-complement-mediated cytotoxicity appeared to be partly determined by the number and rate of loss of antibody-binding sites on the cell surface. These characteristics also correlated with the efficiency of experimental metastasis in the animal. We compared the results reported herein with our previous studies of nonimmune parameters for this series of metastatic variants, and we conclude that immunological differences can be important to the efficiency of lung-colony formation. However, in the case of the second series of variants, despite selection in vitro for resistance to antibody-complement-mediated cell lysis, the behavior of these variants in the lung colony assay could not be predicted by the immunologic parameters examined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00200180
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  • 10
    Electronic Resource
    Electronic Resource
    Immunomodulation and therapeutic characterization of thymosin fraction five (1984)
    Springer
    Cancer immunology immunotherapy 18 (1984), S. 185-194 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this report we describe the characterization of the immunomodulatory efficiency and therapeutic properties of thymosin fraction five (F5). We consistently observed the immunostimulation of T-cell activity in assays of allogeneic mixed lymphocyte response (MLR) and the development of cytotoxic effector cells in an allogeneic mixed lymphocyte tumor response-cell-mediated cytotoxicity assay (MLTR-CMC). No induction of suppressor cell activity was observed. Thymosin F5 also acted successfully as an adjuvant when admixed with irradiated tumor cells. We were unable to demonstrate either NK cell or macrophage activation by thymosin F5. Therapeutic protocols using thymosin F5 and directed against pre-existing experimental and spontaneous metastases, had a significant immunotherapeutic potential.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00205510
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