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Establishment and characterization of human urothelial cancer xenografts in severe combined immunodeficient mice.
Int J Urol. 2006 Jan; 13(1):47-57.IJ

Abstract

AIM

To establish and characterize a murine xenograft model of human urothelial cancer in severe combined immunodeficient (SCID) mice for therapeutic simulation.

METHODS

Pieces of 30 freshly resected urothelial tumors (24 obtained from bladder and 6 from ureter or pelvis) were implanted subcutaneously into SCID mice, and xenograft tumors were passed in tumorigenic cases. At each passage, histopathology, TP53 mutational status assessed by yeast p53 functional assay, and the Ki-67 labeling index (LI) were examined to evaluate the preservation of original features. A growth delay assay after single-dose irradiation was performed in four representative xenografts.

RESULTS

Tumor growth was observed in 18 mice (60%, 18/30). Histologically, 15 of the 18 were epithelial carcinomas similar to the original tumors, whereas the other 3 were Epstein-Barr virus-associated lymphoproliferative disease, resulting in a 50% (15/30) take rate. No correlation was found between the tumor take rate and the clinicopathologic features, TP53 mutational status, or Ki-67 LI of the patients' tumors. Of these 15 xenografts, 11 xenografts were passed from 3 to 10 generations. TP53 mutational status remained stable during the passages, and the Ki-67 LI of eight xenografts was within a range of 50% of the LI of the original tumors, although the other three xenografts increased by over 50%. Specific growth delay after irradiation, independent of the original tumor growth speed and Ki-67 LI, was observed in four xenografts.

CONCLUSIONS

SCID mice are useful recipients for investigations of human urothelial cancer with a wide biological range. This easy-to-handle xenograft system can help to develop a better in vivo preclinical evaluation system for therapeutic agents as well as the investigation of tumor pathophysiology.

Authors+Show Affiliations

Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. takataka@rf6.so-net.ne.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16448432

Citation

Abe, Takashige, et al. "Establishment and Characterization of Human Urothelial Cancer Xenografts in Severe Combined Immunodeficient Mice." International Journal of Urology : Official Journal of the Japanese Urological Association, vol. 13, no. 1, 2006, pp. 47-57.
Abe T, Tada M, Shinohara N, et al. Establishment and characterization of human urothelial cancer xenografts in severe combined immunodeficient mice. Int J Urol. 2006;13(1):47-57.
Abe, T., Tada, M., Shinohara, N., Okada, F., Itoh, T., Hamada, J., Harabayashi, T., Chen, Q., Moriuchi, T., & Nonomura, K. (2006). Establishment and characterization of human urothelial cancer xenografts in severe combined immunodeficient mice. International Journal of Urology : Official Journal of the Japanese Urological Association, 13(1), 47-57.
Abe T, et al. Establishment and Characterization of Human Urothelial Cancer Xenografts in Severe Combined Immunodeficient Mice. Int J Urol. 2006;13(1):47-57. PubMed PMID: 16448432.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Establishment and characterization of human urothelial cancer xenografts in severe combined immunodeficient mice. AU - Abe,Takashige, AU - Tada,Mitsuhiro, AU - Shinohara,Nobuo, AU - Okada,Futoshi, AU - Itoh,Tomoo, AU - Hamada,Jun-Ichi, AU - Harabayashi,Toru, AU - Chen,Qinzhong, AU - Moriuchi,Tetsuya, AU - Nonomura,Katsuya, PY - 2006/2/2/pubmed PY - 2006/6/14/medline PY - 2006/2/2/entrez SP - 47 EP - 57 JF - International journal of urology : official journal of the Japanese Urological Association JO - Int J Urol VL - 13 IS - 1 N2 - AIM: To establish and characterize a murine xenograft model of human urothelial cancer in severe combined immunodeficient (SCID) mice for therapeutic simulation. METHODS: Pieces of 30 freshly resected urothelial tumors (24 obtained from bladder and 6 from ureter or pelvis) were implanted subcutaneously into SCID mice, and xenograft tumors were passed in tumorigenic cases. At each passage, histopathology, TP53 mutational status assessed by yeast p53 functional assay, and the Ki-67 labeling index (LI) were examined to evaluate the preservation of original features. A growth delay assay after single-dose irradiation was performed in four representative xenografts. RESULTS: Tumor growth was observed in 18 mice (60%, 18/30). Histologically, 15 of the 18 were epithelial carcinomas similar to the original tumors, whereas the other 3 were Epstein-Barr virus-associated lymphoproliferative disease, resulting in a 50% (15/30) take rate. No correlation was found between the tumor take rate and the clinicopathologic features, TP53 mutational status, or Ki-67 LI of the patients' tumors. Of these 15 xenografts, 11 xenografts were passed from 3 to 10 generations. TP53 mutational status remained stable during the passages, and the Ki-67 LI of eight xenografts was within a range of 50% of the LI of the original tumors, although the other three xenografts increased by over 50%. Specific growth delay after irradiation, independent of the original tumor growth speed and Ki-67 LI, was observed in four xenografts. CONCLUSIONS: SCID mice are useful recipients for investigations of human urothelial cancer with a wide biological range. This easy-to-handle xenograft system can help to develop a better in vivo preclinical evaluation system for therapeutic agents as well as the investigation of tumor pathophysiology. SN - 0919-8172 UR - https://www.unboundmedicine.com/medline/citation/16448432/Establishment_and_characterization_of_human_urothelial_cancer_xenografts_in_severe_combined_immunodeficient_mice_ L2 - https://doi.org/10.1111/j.1442-2042.2006.01220.x DB - PRIME DP - Unbound Medicine ER -