Recombinant human tumor necrosis factor-alpha: thrombus formation is a cause of anti-tumor activity - PubMed (original) (raw)
. 1988 Feb 15;41(2):243-7.
doi: 10.1002/ijc.2910410215.
Affiliations
- PMID: 3338873
- DOI: 10.1002/ijc.2910410215
Recombinant human tumor necrosis factor-alpha: thrombus formation is a cause of anti-tumor activity
K Shimomura et al. Int J Cancer. 1988.
Abstract
In a previous study we showed that recombinant human tumor necrosis factor-alpha (rTNF-alpha) has no cytolytic effect on Meth A fibrosarcoma cells in vitro but that it has a strong anti-tumor activity in vivo. In the present work, we define the in vivo mode of action of rTNF-alpha on solid-form Meth A fibrosarcoma implanted intradermally (i.d.) in mice. rTNF-alpha exhibited strong anti-tumor activity when given intravenously (i.v.) 7 or 10 days after tumor implantation, but not when given 3 days after implantation. Light and electron microscopy showed that rTNF-alpha impaired microcirculation by producing fibrin-like substances in newly formed microcapillaries in 7-day-old tumor tissue. An anti-coagulant, dicoumarol, abrogated the effect of rTNF-alpha. Injection of carbon particles showed that the development of capillaries in 7-day-old tumors was more extensive than in 3-day-old tumors, and suggested that the anti-tumor activity of rTNF-alpha depends upon a fully developed fine network of induced capillaries in the tumor. Electron microscopy showed that rTNF-alpha increases the number of primary and secondary lysosomes in the cytoplasm of 7-day-old tumor cells. The results suggest that rTNF-alpha selectively stems the blood flow in newly formed microcapillaries, eventually leading to autolysis of the tumor cells.
Similar articles
- Recombinant human tumor necrosis factor-alpha: evidence of an indirect mode of antitumor activity.
Manda T, Shimomura K, Mukumoto S, Kobayashi K, Mizota T, Hirai O, Matsumoto S, Oku T, Nishigaki F, Mori J, et al. Manda T, et al. Cancer Res. 1987 Jul 15;47(14):3707-11. Cancer Res. 1987. PMID: 3594435 - The efficacy of combined treatment with recombinant human tumor necrosis factor-alpha and 5-fluorouracil is dependent on the development of capillaries in tumor.
Manda T, Nishigaki F, Mukumoto S, Masuda K, Nakamura T, Shimomura K. Manda T, et al. Eur J Cancer. 1990 Feb;26(2):93-9. doi: 10.1016/0277-5379(90)90289-6. Eur J Cancer. 1990. PMID: 2138912 - Anti-tumor activity of recombinant tumor necrosis factor on mouse fibrosarcoma in vivo and in vitro.
Tomazic VJ, Farha M, Loftus A, Elias EG. Tomazic VJ, et al. J Immunol. 1988 Jun 1;140(11):4056-61. J Immunol. 1988. PMID: 3372997 - Important role of serotonin in the antitumor effects of recombinant human tumor necrosis factor-alpha in mice.
Manda T, Nishigaki F, Mori J, Shimomura K. Manda T, et al. Cancer Res. 1988 Aug 1;48(15):4250-5. Cancer Res. 1988. PMID: 3390820 - Recombinant human TNF-alpha: preclinical studies and results from early clinical trials.
Saks S, Rosenblum M. Saks S, et al. Immunol Ser. 1992;56:567-87. Immunol Ser. 1992. PMID: 1550875 Review.
Cited by
- Unleashing endogenous TNF-alpha as a cancer immunotherapeutic.
Josephs SF, Ichim TE, Prince SM, Kesari S, Marincola FM, Escobedo AR, Jafri A. Josephs SF, et al. J Transl Med. 2018 Aug 31;16(1):242. doi: 10.1186/s12967-018-1611-7. J Transl Med. 2018. PMID: 30170620 Free PMC article. Review. - Endobiogeny: a global approach to systems biology (part 1 of 2).
Lapraz JC, Hedayat KM. Lapraz JC, et al. Glob Adv Health Med. 2013 Jan;2(1):64-78. doi: 10.7453/gahmj.2013.2.1.011. Glob Adv Health Med. 2013. PMID: 24381827 Free PMC article. Review. - Translational strategies exploiting TNF-alpha that sensitize tumors to radiation therapy.
Mauceri HJ, Beckett MA, Liang H, Sutton HG, Pitroda S, Galka E, Efimova E, Darga T, Khodarev NN, King CR, Posner MC, Hellman S, Kufe DW, Weichselbaum RR. Mauceri HJ, et al. Cancer Gene Ther. 2009 Apr;16(4):373-81. doi: 10.1038/cgt.2008.86. Epub 2008 Oct 31. Cancer Gene Ther. 2009. PMID: 18974777 Free PMC article. - Chimeric form of tumor necrosis factor-alpha has enhanced surface expression and antitumor activity.
Rieger R, Whitacre D, Cantwell MJ, Prussak C, Kipps TJ. Rieger R, et al. Cancer Gene Ther. 2009 Jan;16(1):53-64. doi: 10.1038/cgt.2008.57. Epub 2008 Jul 25. Cancer Gene Ther. 2009. PMID: 18654609 Free PMC article. - Synergistic antitumor effect of an angiogenesis inhibitor (TNP-470) and tumor necrosis factor in mice.
Amikura K, Matsuno S, Egawa S. Amikura K, et al. Surg Today. 2006;36(12):1069-74. doi: 10.1007/s00595-006-3289-3. Epub 2006 Dec 25. Surg Today. 2006. PMID: 17123135
MeSH terms
Substances
LinkOut - more resources
Full Text Sources