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  • 1
    Electronic Resource
    Electronic Resource
    Mode of antitumor action of recombinant human tumor necrosis factor on the sarcoma Meth A transplanted in the mouse (1989)
    Springer
    Biotherapy 1 (1989), S. 47-57 
    Details
    ISSN: 1573-8280
    Keywords: cytotoxicity ; Meth A sarcoma ; mode of action ; tumor necrosis factor ; vasculan collapse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mode of antitumor action of rHu-TNF was elucidated in BALB/c mice bearing Meth A fibrosarcoma 7 days after transplantation with respect to time course, dose-response relationships and selectivity of the effects. The maximal cytotoxic effect on tumor cells revealed by inhibition of DNA synthesis and maximal lesional effect on tumor vasculature revealed by change in blood pool-size in the tissue were detected at 30 min and I h after administration of rHu-TNF, respectively. The dose-response relationship between cytotoxic and tumoricidal effects of rHu-TNF was irrespective of administration route. ED50s of these antitumor effects afteri.v. administration of rHu-TNF were about 50 times as high as ED50s afteri.t. administration. ED50 ofi.t. given rHu-TNF for vascular effect was about 20 times as high as that for cytotoxicity while ED50 ofi.v. rHu-TNF for vascular effect was only 2–3 times as high as that for cytotoxicity. The whole body autoradiographies with [125I] HSA giveni.v. to see the blood influx into tumor tissue and [14C]thymidine given i.v. to see DNA synthesis in the whole body after administration of rHu-TNF revealed that the distribution of radioactivity was markedly changed in the tumor alone without any detectable change in other whole body tissues. In conclusion, thein vivo antitumor effect of rHu-TNF giveni.t. ori.v., appears to be exerted through the direct action on Meth A sarcoma rather than indirectly on tumor vasculature. Under present conditions, the effect of rHu-TNF in the whole body tissues seems rather selective on cells and vasculature of the tumor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02170135
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  • 2
    Electronic Resource
    Electronic Resource
    Interleukin-1α: Its possible roles in cancer therapy (1989)
    Springer
    Biotherapy 1 (1989), S. 327-338 
    Details
    ISSN: 1573-8280
    Keywords: antitumor activity ; augmentation of host resistance to infections ; cancer therapy ; myelorestorative activity ; recombinant interleukin-1α
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Our studies on recombinant human IL-1α polypeptide were summarized with respect to molecular cloning, production, quantitative assay systems, antitumor activity, myelorestorative activity and augmentation of host resistance to infections. Recombinant human IL-1α (18 kDa) was produced through the expression of the cloned human IL-1α cDNA inEscherichia coli and purified to an endotoxin-free homogeneous polypeptide. The human IL-1α inhibited dose-dependently the growth of syngeneic murine tumors transplanted in mice and completely regressed the tumors in some cases, and its antitumor activity was significantly enhanced in combination with indomethacin. The human IL-1α accelerated the recovery of the numbers of peripheral leukocytes and neutrophils in a dose-dependent manner at a dose as low as 10 ng/mouse/day in myelo suppressed mouse model produced by administering anticancer chemotherapeutic drugs. The myelorestorative effect of IL-1α was observed not only on leukocytes/neutrophils, but also on platelets in myelosuppressed mice. In addition, the human IL-1α markedly augmented dose-dependently resistance of normal and leukopenic mice to various microbial infections. These results suggested that recombinant human IL-1α might be useful for cancer therapy from the viewpoints of improving adverse effects such as myelosuppression caused by chemotherapy and/or radiation therapy and preventing infections. In addition, use of IL-1α may permit more intensive chemo- and radiation therapies using higher doses. Finally, the antitumor activity of the IL-1α itself may play an important role.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02171009
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Disposition of125I-labeled recombinant human tumor necrosis factor in the tumor-bearing mouse (1989)
    Springer
    Biotherapy 1 (1989), S. 7-18 
    Details
    ISSN: 1573-8280
    Keywords: disposition ; distribution ; excretion ; Meth A sarcoma ; pharmacokinetics ; tumornecrosis factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Disposition of [125I]rHu-TNF was elucidated in BALB/c mice bearing Meth A fibrosarcoma 7 days after transplantation. Afteri.v. administration, [125I]rHu-TNF measured by radioactivity and immunoreactivity biphasically decreased in plasma. Tumor level of [125I]rHu-TNF was the maximum at 1 h, then decreased and finally remained essentially constant. After i.t. administration, plasma level reached the maximum at 1 h. Tumor level decreased quickly and then became essentially constant. [125I]rHu-TNF was suggested to be degraded to small fragments in the tumor. Significant distribution of [125I]rHu-TNF was found in the kidney, lung, liver and tumor. Most tissue levels decreased with time in parallel with plasma levels. [125I]rHu-TNF radioactivity was found in proximal convoluted tubules of kidney and in those areas of tumor consisting of degenerating cells with pyknotic nuclei. Urine contained most of administered radioactivity, which being neither immunoreactive nor protein-bound.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02170131
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Clinical studies with TNF (1991)
    Springer
    Biotherapy 3 (1991), S. 177-186 
    Details
    ISSN: 1573-8280
    Keywords: antitumor response ; clinical trials ; pharmacokinetics ; toxicity ; tumor necrosis factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02172090
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    Paper (German National Licenses)
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