Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Jun 15;88(12):5163–5166. doi: 10.1073/pnas.88.12.5163

Correlation of histology and drug response of human tumors grown in native-state three-dimensional histoculture and in nude mice.

R A Vescio 1, K M Connors 1, T Kubota 1, R M Hoffman 1
PMCID: PMC51832  PMID: 2052596

Abstract

An in vitro histoculture system in which a native-state collagen-sponge gel supports the three-dimensional growth of tumor tissue has been recently developed that allows the culture and drug response assay for most every tumor type. Important features of the histoculture system include the maintenance of three-dimensional tissue architecture and the use of histological autoradiography to measure nuclear incorporation of [3H]thymidine as an endpoint. We describe in this report in vitro-in vivo correlations for drug response and tumor histology by using human tumor xenografts grown in the native-state three-dimensional histoculture system and as xenografts in nude mice. This comparison eliminates many of the confounding variables seen in most correlative clinical trials. Results demonstrate (i) a very high preservation of in vivo tissue architecture in vitro, (ii) an 86% accuracy in vitro of predicting drug resistance in vivo using suprapharmacologic doses of drugs in vitro, and (iii) an overall predictive frequency of drug resistance and sensitivity ranging from 53% for 5-fluorouracil to 78% for doxorubicin.

Full text

PDF
5166

Images in this article

5164Image
on p.5164
5164Image
on p.5164
5164Image
on p.5164
5164Image
on p.5164

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Freeman A. E., Hoffman R. M. In vivo-like growth of human tumors in vitro. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2694–2698. doi: 10.1073/pnas.83.8.2694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Hoffman R. M., Connors K. M., Meerson-Monosov A. Z., Herrera H., Price J. H. A general native-state method for determination of proliferation capacity of human normal and tumor tissues in vitro. Proc Natl Acad Sci U S A. 1989 Mar;86(6):2013–2017. doi: 10.1073/pnas.86.6.2013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Hoffman R. M. In vitro sensitivity assays in cancer: a review, analysis, and prognosis. J Clin Lab Anal. 1991;5(2):133–143. doi: 10.1002/jcla.1860050211. [DOI] [PubMed] [Google Scholar]
  4. Kern D. H., Weisenthal L. M. Highly specific prediction of antineoplastic drug resistance with an in vitro assay using suprapharmacologic drug exposures. J Natl Cancer Inst. 1990 Apr 4;82(7):582–588. doi: 10.1093/jnci/82.7.582. [DOI] [PubMed] [Google Scholar]
  5. Kubota T., Nakada M., Tsuyuki K., Inada T., Asanuma F., Ishibiki K., Abe O. Cell kinetics and chemosensitivity of human carcinomas serially transplanted into nude mice. Jpn J Cancer Res. 1986 May;77(5):502–507. [PubMed] [Google Scholar]
  6. Perrapato S. D., Slocum H. K., Huben R. P., Ghosh R., Rustum Y. Assessment of human genitourinary tumors and chemosensitivity testing in 3-dimensional collagen gel culture. J Urol. 1990 May;143(5):1041–1045. doi: 10.1016/s0022-5347(17)40179-0. [DOI] [PubMed] [Google Scholar]
  7. Phillips R. M., Bibby M. C., Double J. A. A critical appraisal of the predictive value of in vitro chemosensitivity assays. J Natl Cancer Inst. 1990 Sep 19;82(18):1457–1468. doi: 10.1093/jnci/82.18.1457. [DOI] [PubMed] [Google Scholar]
  8. Vescio R. A., Connors K. M., Bordin G. M., Robb J. A., Youngkin T., Umbreit J. N., Hoffman R. M. The distinction of small cell and non-small cell lung cancer by growth in native-state histoculture. Cancer Res. 1990 Sep 15;50(18):6095–6099. [PubMed] [Google Scholar]
  9. Vescio R. A., Connors K. M., Youngkin T., Bordin G. M., Robb J. A., Umbreit J. N., Hoffman R. M. Cancer biology for individualized therapy: correlation of growth fraction index in native-state histoculture with tumor grade and stage. Proc Natl Acad Sci U S A. 1990 Jan;87(2):691–695. doi: 10.1073/pnas.87.2.691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Vescio R. A., Redfern C. H., Nelson T. J., Ugoretz S., Stern P. H., Hoffman R. M. In vivo-like drug responses of human tumors growing in three-dimensional gel-supported primary culture. Proc Natl Acad Sci U S A. 1987 Jul;84(14):5029–5033. doi: 10.1073/pnas.84.14.5029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Von Hoff D. D. He's not going to talk about in vitro predictive assays again, is he? J Natl Cancer Inst. 1990 Jan 17;82(2):96–101. doi: 10.1093/jnci/82.2.96. [DOI] [PubMed] [Google Scholar]
  12. Von Hoff D. D., Sandbach J. F., Clark G. M., Turner J. N., Forseth B. F., Piccart M. J., Colombo N., Muggia F. M. Selection of cancer chemotherapy for a patient by an in vitro assay versus a clinician. J Natl Cancer Inst. 1990 Jan 17;82(2):110–116. doi: 10.1093/jnci/82.2.110. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES