Skip to main content

Development of the Histoculture Drug Response Assay (HDRA)

  • Protocol
  • First Online:
Book cover 3D Sponge-Matrix Histoculture

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1760))

Abstract

The histoculture drug response assay (HDRA) was developed using Gelfoam® histoculture of all tumor types. Twenty tumor classes, including all the major ones, have been histocultured on Gelfoam® and tested for drug response. Quantitative and qualitative results show increasing cell kill with rising cytotoxic drug concentration, differential drug sensitivities of multiple cell types within individual cultured tumors, differential sensitivities to a single drug of a series of tumors of the same histopathological classification, differential sensitivities of individual tumors to a series of drugs, and sensitivity patterns of various tumor types similar to the sensitivities found in vivo. Therefore, the results indicated that precise therapeutic data can be obtained from tumor specimens growing in Gelfoam® histoculture in vitro for the individual cancer patient as well as for rational and relevant screening for novel agents active against human solid tumors.

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

Access this chapter

eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Chabner BA (ed) (1983) Rational basis for chemotherapy. Liss, New York

    Google Scholar 

  2. Finlay GJ, Baguley BC (1984) The use of human cancer cell lines as a primary screening system for antineoplastic compounds. Eur J Cancer Clin Oncol 20:947–954

    Article  CAS  PubMed  Google Scholar 

  3. Hamburger AW, Salmon SE (1977) Primary bioassay of human tumor stem cells. Science 197:461–463

    Article  CAS  PubMed  Google Scholar 

  4. Salmon SE, Hamburger AW, Soehnlen B, Durie BG, Alberts DS, Moon TE (1978) Quantitation of differential sensitivity of human-tumor stem cells to anticancer drugs. N Engl J Med 298:1321–1327

    Article  CAS  PubMed  Google Scholar 

  5. Twentyman PR (1985) Predictive chemosensitivity testing. Br J Cancer 51:295–299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Selby P, Buick RN, Tannock I (1983) A critical appraisal of the “human tumor stem-cell assay”. N Engl J Med 308:129–134

    Article  CAS  PubMed  Google Scholar 

  7. Von Hoff DD (1983) Send this patient's tumor for culture and sensitivity. N Engl J Med 308:154–155

    Article  Google Scholar 

  8. Pihl A, UICC Study Group on chemosensitivity testing of human tumors (1986) Problems—applications—future prospects. Int J Cancer 37:1–5

    Article  CAS  PubMed  Google Scholar 

  9. Singletary SE, Umbach GE, Spitzer G, Drewinko B, Tomasovic B, Ajani J, Hug V, Blumenschein G (1985) The human tumor stem cell assay revisited. Int J Cell Cloning 3:116–128

    Article  CAS  PubMed  Google Scholar 

  10. Baker FL, Spitzer G, Ajani JA, Brock WA, Lukeman J, Pathak S, Tomasovic B, Thielvoldt D, Williams M, Vines C et al (1986) Drug and radiation sensitivity measurements of successful primary monolayer culturing of human tumor cells using cell-adhesive matrix and supplemented medium. Cancer Res 46:1263–1274

    CAS  PubMed  Google Scholar 

  11. Wilson AP, Ford CH, Newman CE, Howell A (1984) A comparison of three assays used for the in vitro chemosensitivity testing of human tumours. Br J Cancer 49:57–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Smith HS, Lippman ME, Hiller AJ, Stampfer MR, Hackett AJ (1985) Response to doxorubicin of cultured normal and cancerous human mammary epithelial cells. J Natl Cancer Inst 74:341–347

    CAS  PubMed  Google Scholar 

  13. Tofilon PJ, Buckley N, Deen DF (1984) Effect of cell-cell interactions on drug sensitivity and growth of drug-sensitive and -resistant tumor cells in spheroids. Science 226:862–864

    Article  CAS  PubMed  Google Scholar 

  14. Erlichman C, Vidgen D (1984) Cytotoxicity of adriamycin in MGH-U1 cells grown as monolayer cultures, spheroids, and xenografts in immune-deprived mice. Cancer Res 44:5369–5375

    CAS  PubMed  Google Scholar 

  15. Zaffaroni N, Silvestrini R, Sanfilippo O, Daidone MG, Gasparini G (1985) In vitro activity of alkylating agents on human tumors as measured by a short-term antimetabolic assay. Tumori 71:555–561

    CAS  PubMed  Google Scholar 

  16. Volm M, Wayss K, Kaufmann M, Mattern J (1979) Pretherapeutic detection of tumour resistance and the results of tumour chemotherapy. Eur J Cancer 15:983–993

    Article  CAS  PubMed  Google Scholar 

  17. Weisenthal LM, Marsden JA, Dill PL, Macaluso CK (1983) A novel dye exclusion method for testing in vitro chemosensitivity of human tumors. Cancer Res 43:749–757

    CAS  PubMed  Google Scholar 

  18. Leighton J (1960) The propagation of aggregates of cancer cells: implications for therapy and a simple method of study. Cancer Chemother Rep 9:71–72

    CAS  PubMed  Google Scholar 

  19. Leighton J, Kalla R, Turner JM Jr, Fennell RH Jr (1960) Pathogenesis of tumor invasion. II. Aggregate replication. Cancer Res 20:575–586

    CAS  PubMed  Google Scholar 

  20. Leighton J (1959) Aggregate replication, a factor in the growth of cancer. Science 129(3347):466–467

    Article  CAS  PubMed  Google Scholar 

  21. Leighton J, Kalla R, Kline I, Belkin M (1959) Pathogenesis of tumor invasion. I. Interaction between normal tissues and transformed cells in tissue culture. Cancer Res 19(1):23–27

    CAS  PubMed  Google Scholar 

  22. Dawe CJ, Potter M, Leighton J (1958) Progressions of a reticulum-cell sarcoma of the mouse in vivo and in vitro. J Natl Cancer Inst 21(4):753–781

    CAS  PubMed  Google Scholar 

  23. Leighton J (1957) Contributions of tissue culture studies to an understanding of the biology of cancer: a review. Cancer Res 17(10):929–941

    CAS  PubMed  Google Scholar 

  24. Kline I, Leighton J, Belkin M, Orr HC (1957) Some observations on the response of four established human cell strains to hydrocortisone in tissue culture. Cancer Res 17(8):780–784

    CAS  PubMed  Google Scholar 

  25. Leighton J, Kline I, Belkin M, Legallais F, Orr HC (1957) The similarity in histologic appearance of some human cancer and normal cell strains in sponge-matrix tissue culture. Cancer Res 17(5):359–363

    CAS  PubMed  Google Scholar 

  26. Leighton J, Kline I, Belkin M, Orr HC (1957) Effects of a podophyllotoxin derivative on tissue culture systems in which human cancer invades normal tissue. Cancer Res 17(4):336–344

    CAS  PubMed  Google Scholar 

  27. Leighton J, Kline I, Belkin M, Tetenbaum Z (1956) Studies on human cancer using sponge-matrix tissue culture. III. The invasive properties of a carcinoma (strain HeLa) as influenced by temperature variations, by conditioned media, and in contact with rapidly growing chick embryonic tissue. J Natl Cancer Inst 16(6):1353–1373

    CAS  PubMed  Google Scholar 

  28. Leighton J, Kline I, Orr HC (1956) Transformation of normal human fibroblasts into histologically malignant tissue in vitro. Science 123(3195):502

    Article  CAS  PubMed  Google Scholar 

  29. Leighton J (1954) The growth patterns of some transplantable animal tumors in sponge matrix tissue culture. J Natl Cancer Inst 15(2):275–293

    CAS  PubMed  Google Scholar 

  30. Leighton J, Kline I (1954) Studies on human cancer using sponge matrix tissue culture. II. Invasion of connective tissue by carcinoma (strain HeLa). Tex Rep Biol Med 12(4):865–873

    CAS  PubMed  Google Scholar 

  31. Leighton J (1954) Studies on human cancer using sponge matrix tissue culture. I. The growth patterns of a malignant melanoma, adenocarcinoma of the parotid gland, papillary adenocarcinoma of the thyroid gland, adenocarcinoma of the pancreas, and epidermoid carcinoma of the uterine cervix (Gey's HeLa strain). Tex Rep Biol Med 12(4):847–864

    CAS  PubMed  Google Scholar 

  32. Leighton J (1951) A sponge matrix method for tissue culture; formation of organized aggregates of cells in vitro. J Natl Cancer Inst 12(3):545–561

    CAS  PubMed  Google Scholar 

  33. Browning TH, Trier TS (1969) Organ culture of mucosal biopsies of human small intestine. J Clin Invest 48:1248

    Article  Google Scholar 

  34. Schiff LJ (1975) Organ cultures of rat and hamster colon. In Vitro 11:46

    Article  CAS  PubMed  Google Scholar 

  35. Autrup H (1980) Explant culture of human colon. In: Methods in cell biology, vol 2lB. Academic Press, New York, p 335

    Google Scholar 

  36. Autrup H (1983) In: Autrup H, Williams H (eds) Experimental colon carcinogenesis. CRC Press, Boca Raton

    Google Scholar 

  37. Sherwin RP, Richters A, Yellin AE, Donovan AJ (1980) Histoculture of human breast cancers. J Surg Oncol 13:9–20

    Article  CAS  PubMed  Google Scholar 

  38. Folkman J, Hochberg M (1973) Self-regulation of growth in three dimensions. J Exp Med 138(4):745–753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Carrel A (1912) On the permanent life of tissues outside of the organism. J Exp Med 15:516–528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yoshida Y, Hillborn V, Hassett C, Melti P, Byers MJ, Freeman AE (1980) Characterization of mouse fetal lung cells cultured on a pigskin substrate. In Vitro 16:443–445

    Google Scholar 

  41. Yoshida Y, Hillborn V, Freeman AE (1980) Fine structure identification of organoid mouse lung cells cultured on a pigskin substrate. In Vitro 16:994–1006

    Article  CAS  PubMed  Google Scholar 

  42. Douglas WHJ, McAteer JA, Cavanagh T (1978) Organotypic culture of dissociated fetal rat lung cells on a collagen sponge matrix. Tissue Cult Assoc Manual 4:749–753

    Article  Google Scholar 

  43. Vescio RA, Redfern CH, Nelson TJ, Ugoretz S, Stern PH, Hoffman RM (1987) In vivo-like drug responses of human tumors growing in three-dimensional gel-supported, primary culture. Proc Natl Acad Sci U S A 84:5029–5033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Chabner B (1982) Pharmacologic principles of cancer treatment. Saunders, Philadelphia

    Google Scholar 

  45. Alberts DS, Chen GHS (1980) Cloning of human tumor stem cells. Salmon SE. Liss, New York, pp 351–359

    Google Scholar 

  46. Hamilton E, Dobbin J (1982) [3H]thymidine labels less than half of the DNA-synthesizing cells in the mouse tumour, carcinoma NT. Cell Tissue Kinet 15:405–411

    CAS  PubMed  Google Scholar 

  47. Scully RE (ed) (1979) Tumors of the ovary and maldeveloped gonads, Atlas of Tumor Pathology, 2nd Series Fascicle 16. Armed Forces Institute of Pathology, Washington, DC

    Google Scholar 

  48. Haskell CM (ed) (1985) Cancer treatment, 2nd edn. Saunders, Philadelphia

    Google Scholar 

  49. Freeman A, Hoffman RM (1986) In vivo-like growth of human tumors in vitro. Proc Natl Acad Sci U S A 83:2694–2698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Miller BE, Miller FR, Heppner GH (1981) Interactions between tumor subpopulations affecting their sensitivity to the antineoplastic agents cyclophosphamide and methotrexate. Cancer Res 41(11 Pt 1):4378–4381

    CAS  PubMed  Google Scholar 

  51. Bhatia S, Frangioni JV, Hoffman RM, Iafrate AJ, Polyak K (2012) The challenges posed by cancer heterogeneity. Nat Biotechnol 30:604–610

    Article  CAS  PubMed  Google Scholar 

  52. Parikh RB, Schwartz JS, Navathe AS (2017) Beyond genes and molecules – A precision delivery initiative for precision medicine. N Engl J Med 376:1609–1612

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robert M. Hoffman .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Hoffman, R.M., Vescio, R.A. (2018). Development of the Histoculture Drug Response Assay (HDRA). In: Hoffman, R. (eds) 3D Sponge-Matrix Histoculture. Methods in Molecular Biology, vol 1760. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7745-1_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7745-1_5

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7743-7

  • Online ISBN: 978-1-4939-7745-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics