Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Evaluation of response to chemotherapy in retinoblastoma heterotransplanted to the eyes of nude mice

Summary

The role of chemotherapy in the treatment of retinoblastoma (RB) is unsatisfactory and clinical research is severely limited. A xenograft model for testing chemotherapeutic and other atents has been developed by the heterotransplantation of human RB cells into the anterior chamber of the nude mouse eye. A grading system for visually monitored tumor growth was designed to allow serial observations and documentation of the response to therapy in the model. This method of monitoring compared favorably with histopathologic, photographic, or other criteria in the reproducible, sequential evaluation of tumor status. Six chemotherapeutic agents [vincristine (VCR), doxorubicin (DOX), actinomycin D (ACT-D), dimethyltriazeno-imidazole carboxamide (DTIC), cyclosphosphamide (CMP), and diaziquone (AZQ)] were then tested in the model against a patient-derived xenograft line. Results were expressed as the delay in tumor progression judged by serial grading. CPM produced a consistent response in all treated tumors, as did DTIC to a lesser, more variable extent. In 3 of 10 tumors treated with CPM and in 1 of 18 treated with DTIC, complete responses were maintained for at least 20 weeks. VCR, DOX, and ACT-D were ineffective, producing patterns of tumor progression no different from those in the control group. AZQ was most effective, producing responses far exceeding those of conventional agents. The model allows quantitative documentation of the response to therapy in heterotransplanted human RB. Further testing of new agents and combinations is warranted. AZQ may be active against RB.

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

References

  1. 1.

    Benedict WF, Dawson JA, Banerjee A, Murphree AL (1980) The nude mouse model for human retinoblastoma: a system for evaluation of retinoblastoma therapy. Med Pediatr Oncol 8: 391

  2. 2.

    Benedict WF, Lingua RW, Doiron DR, Dawson JA, Murphree AL (1980) Tumour regression of human retinoblastoma in the nude mouse following photoradiation therapy: a preliminary report. Med Pediatr Oncol 8: 397

  3. 3.

    Bender JF, Grillo-Lopez AJ, Posada JG (1983) Diaziquone (AZQ). Invest New Drugs 1: 71

  4. 4.

    Chou F, Khan AH, Driscoll JS (1976) Potential central nervous system antitumor agents. Aziridinylbenzoquinones II. J Med Chem 19: 1302

  5. 5.

    Clinical Brochure (1979) Aziridinylbenzoquinone (NSC-182986). National Cancer Institute, Bethesda, Md (revised July 1983)

  6. 6.

    Gallie BL, Albert DM, Wong JJY, Buyukmihei N, Puliafito CA (1977) Heterotransplantation of retinoblastoma into the athymic “nude” mouse. Invest Ophthalmol Vis Sci 16: 256

  7. 7.

    Gallie BL, Wong J, Hol, Good R, Kitchin D, Elloworth R (1978) Athymic nude mouse model of retinoblastoma. Jpn J Ophthalmol 22: 345

  8. 8.

    Gallie BL, Chew EY, Chang M, Phillips RA (1982) Retinoblastoma in the eyes of nude mice: quantitative assessment of therapy. In: Proceedings of the 3rd international workshop on nude mice. Gustav Fischer, New York, p 227

  9. 9.

    Lonsdale D, Berry DH, Holcomb TM (1968) Chemotherapeutic trials in patients with metastatic retinoblastoma. Cancer Chemother Rep 56 (6): 631

  10. 10.

    Ragab AH, Sutow WW, Komp DM (1975) Adriamycin in the treatment of childhood solid tumors. Cancer 36: 1572

  11. 11.

    Szirth BC, White L, Benedict WF (1983) Photographic documentation of human retinoblastoma transplanted into the anterior chamber of the athymic “nude” mouse eye. Ophthalmol Photogr 6: 76

  12. 12.

    White L (1983) The role of chemotherapy in the treatment of retinoblastoma. Retina 3: 194

  13. 13.

    White L, Meyer PR, Benedict WF (1984) Establishment and characterization of a human T-cell leukemia line (LALW-2) in nude mice. J Natl Cancer Inst 72: 1029

  14. 14.

    White L, Ortega JA, Ying KL (1985) Acute nonlymphocytic leukemia following multimodality therapy for retinoblastoma. Cancer 55: 496

  15. 15.

    White L, Chan K, Barrintos A, Benedict W (1987) Tissue distribution of doxorubicin in experimental animals and xenografted human retinoblastoma. Med Pediatr Oncol 15: 140

  16. 16.

    White L, Gomer CJ, Doiron DR, Szirth BC (1988) Ineffective photodynamic therapy in a poorly vascularized xenograft model. Br J Cancer 57: 455

  17. 17.

    Wolff JA, Pratt CB, Sitarz AL (1975) Chemotherapy of metastatic retinoblastoma. Cancer Chemother Rep 16: 435

Download references

Author information

Correspondence to Les White.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

White, L., Szirth, B.C. & Benedict, W.F. Evaluation of response to chemotherapy in retinoblastoma heterotransplanted to the eyes of nude mice. Cancer Chemother. Pharmacol. 23, 63–67 (1989). https://doi.org/10.1007/BF00273518

Download citation

Keywords

  • Doxorubicin
  • Nude Mouse
  • Vincristine
  • Anterior Chamber
  • Retinoblastoma