Skip to main content

Advertisement

SpringerLink
Log in

Tumor inhibition by titanocene complexes: influence on xenografted human adenocarcinomas of the gastrointestinal tract

  • Original Articles
  • Titanocene Complexes, Xenografted Human Adenocarcinoma, Gastrointestinal Tract
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

The present study deals with the influence of some bis(η5-cyclopentadienly)titanium(IV) (titanocene) complexes, mainly represented by titanocene dichloride, on the development of several human gastrointestinal (GI) carcinomas (one stomach, seven colon, four sigmoid, and two rectal adenocarcinomas), all xenografted to athymic mice. In 10 of these 14 carcinomas, titanocene dichloride effected growth suppression of >50% in comparison with control tumors. In the case of the stomach and two colon adenocarcinomas, absolute decreases in tumor volume occurred during and after the treatment period, resulting in growth delays of 6, 14, and 31 days, respectively. No sensitivity dependence was observed in the degree of tumor differentiation. The findings of the present study confirm the tumor-inhibiting activity of titanocene complexes against human GI adenocarcinomas. These results are noteworthy in view of previous clinical and experimental experience indicating that human adenocarcinomas of the stomach and colon are generally rather insensitive to common cytostatic agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bastert GB, Fortmeyer HP, Schmidt-Matthiesen H (1981) Thymus aplastic nude mice and rats in clinical oncology. Gustav Fischer Verlag, Stuttgart, New York

    Google Scholar 

  2. Bellet RE, Danna V, Mastrangelo MJ, Berd D (1979) Evaluation of a “nude” mouse-human tumor panel as a predicitive secondary screen for cancer chemotherapeutic agents. J Natl Cancer Inst 63:1185–1188

    Google Scholar 

  3. Biran S, Biran H (1981) Mitomycin-C combinations in the treatment of advanced gastrointestinal carcinoma. In: Mitomycin-C in clinical oncology. Kyowa Hakko Kogyo, Co. Ltd., Tokyo, pp 19–26

    Google Scholar 

  4. Döppert K, Sanchez-Delgado R, Klein HP, Thewalt U (1982) Darstellung, Struktur und Eigenschaften von Bis(cyclopentadienyl)oxalatotitan(IV) und Bis(cyclopentadienyl)bis(hydrogenmaleinato)titan(IV). J Organomet Chem 233:205–213

    Google Scholar 

  5. Fiebig HH, Löhr GW (1984) Wachstum menschlicher Malignome und Entwicklung von tumormodellen in der thymusaplastischen Nacktmaus. Beitr Onkol 18:287–314

    Google Scholar 

  6. Fiebig HH, Schuchhardt C, Heuss H, Fiedler L, Löhr GW (1984) Comparison of tumor response in nude mice and in patients. Behring Inst Mitt 74:343–352

    Google Scholar 

  7. Köpf-Maier P (1987) Tumor inhibition by titanocene complexes: influence upon xenografted human lung carcinomas. J Cancer Res Clin Oncol 113:342–348

    Google Scholar 

  8. Köpf-Maier P (1988) Histologic and ultrastructural alterations of a xenografted human colon adenocarcinoma after treatment with titanocene dichloride. J Cancer Res Clin Oncol 114:250–258

    Google Scholar 

  9. Köpf-Maier P, Köpf H (1987) Tumor inhibition by titanocene complexes: activity against B16 melanoma and colon 38 carcinoma. Drug Res/Arzneim-Forsch 37:532–534

    Google Scholar 

  10. Köpf-Maier P, Köpf H (1987) Non-platinum-group metal antitumor agents: history, current status and perspectives. Chem Rev 87:1137–1152

    Google Scholar 

  11. Köpf-Maier P, Hesse B, Voigtländer R, Köpf H (1980) Tumor inhibition by metallocenes: antitumor activity of titanocene dihalides (C5H5)2TiX2 (X=F, Cl, Br, I, NCS) and their application in buffered solutions as a method for suppressing drug-induced side effects. J Cancer Res Clin Oncol 97:31–39

    Google Scholar 

  12. Köpf-Maier P, Wagner W, Hesse B, Köpf H (1981) Tumor inhibition by metallocenes: activity against leukemias and detection of the systemic effect. Eur J Cancer 17:665–669

    Google Scholar 

  13. Köpf-Maier P, Moormann A, Köpf H (1985) Activity of titanocene dihalides against a human colon carcinoma heterotransplanted to athymic mice. Eur J Cancer Clin Oncol 21: 853–857

    Google Scholar 

  14. Köpf-Maier P, Grabowski S, Liegener J, Köpf H (1985) New antitumor titanocene derivatives containing hydrophilic ligands. Inorg Chim Acta 108:99–103

    Google Scholar 

  15. Köpf-Maier P, Preiß F, Marx T, Klapötke T, Köpf H (1986) Tumor inhibition by titanocene complexes: activity against sarcoma 180. Anticancer Res 6:33–38

    Google Scholar 

  16. Moertel CG (1975) Clinical management of advanced gastrointestinal cancer. Cancer 36:675–682

    Google Scholar 

  17. Nowak K, Peckham MJ, Steel GG (1978) Variation in response of xenografts of colo-rectal carcinoma to chemotherapy. Br J Cancer 37:576–584

    Google Scholar 

  18. Osieka R, Houchens DP, Goldin A, Johnson RK (1977) Chemotherapy of human colon cancer xenografts in athymic nude mice. Cancer 40:2640–2650

    Google Scholar 

  19. Povlsen CO, Rygaard J (1971) Heterotransplantation of human adenocarcinomas of the colon and rectum to the mouse mutant nude. A study of nine consecutive transplantations. Acta Pathol Microbiol Scand A 79:159–169

    Google Scholar 

  20. Rygaard J, Povlsen CO (1982) Athymic (nude) mice. In: Foster HL (eds.) The mouse in biomedical research, vol IV. Academic Press, New York, pp 51–67

    Google Scholar 

  21. Samuel E (1966) Les complexes-π des métaux de la colonne IV A avec le cyclopentadiène, l'indène et le fluorène. Bull Soc Chim Belg: 3548–3564

  22. Shorthouse AJ, Smyth JF, Steel GG, Ellison M, Mills J, Peckham MJ (1980) The human tumour xenograft—a valid model in experimental chemotherapy? Br J Surg 67:715–722

    Google Scholar 

  23. Wilkinson G, Birmingham JM (1954) bis-Cyclopentadienyl compounds of Ti, Zr, V, Nb, and Ta. J Am Chem Soc 76: 4281–4284

    Google Scholar 

  24. Wolpert-DeFilippes MK (1979) Antitumor activity of cis-dichlorodiammineplatinum(II). Cancer Treat Rep 63: 1453–1458

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Anatomie, Freie Universität Berlin, Königin-Luise-Strasse 5, D-1000, Berlin 33, Germany

    P. Köpf-Maier

Authors
  1. P. Köpf-Maier
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Köpf-Maier, P. Tumor inhibition by titanocene complexes: influence on xenografted human adenocarcinomas of the gastrointestinal tract. Cancer Chemother. Pharmacol. 23, 225–230 (1989). https://doi.org/10.1007/BF00451646

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00451646

Keywords

Search

Navigation