Clinical Usefulness of the Histoculture Drug Response Assay for Prostate Cancer and Benign Prostate Hypertrophy (BPH)

  • Robert M. Hoffman
Part of the Methods in Molecular Biology book series (MIMB, volume 1760)


The histoculture drug response assay (HDRA) has been adapted to determine androgen sensitivity in Gelfoam histoculture of human benign prostatic tissue as well as prostate cancer. Gelfoam histoculture was used to measure androgen-independent and androgen-dependent growth of benign and malignant prostate tissue. The androgen-sensitivity index was significantly higher in 23 paired specimens of prostate cancer compared to benign prostate hypertrophy (BPH). Genistein decreased the androgen-sensitivity index of BPH and prostate cancer in Gelfoam® histoculture in a dose-dependent manner.

Key words

Gelfoam® histoculture Prostate cancer Benign prostate hypertrophy (BPH) Dihydrotestosterone (DHT) Hydroxyflutamide (HF) DHT/HF index Androgen-sensitivity index 


  1. 1.
    Logothetis CJ (2017) Improved outcomes in men with advanced prostate cancer. N Engl J Med 377:388–390CrossRefPubMedGoogle Scholar
  2. 2.
    Geller J, Sionit LR, Connors K, Hoffman RM (1992) Measurement of androgen sensitivity in the human prostate in in vitro three-dimensional histoculture. Prostate 21:269–278CrossRefPubMedGoogle Scholar
  3. 3.
    Furukawa T, Kubota T, Hoffman RM (1995) Clinical applications of the histoculture drug response assay. Clin Cancer Res 1:305–311PubMedGoogle Scholar
  4. 4.
    Kubota T, Sasano N, Abe O, Nakao I, Kawamura E, Saito T, Endo M, Kimura K, Demura H, Sasano H, Nagura H, Ogawa N, Hoffman RM (1995) Potential of the histoculture drug response assay to contribute to cancer patient survival. Clin Cancer Res 1:1537–1543PubMedGoogle Scholar
  5. 5.
    Tanino H, Oura S, Hoffman RM, Kubota T, Furukawa T, Arimoto J, Yoshimasu T, Hirai I, Bessho T, Suzuma T, Sakurai T, Naito Y (2001) Acquisition of multidrug resistance in recurrent breast cancer demonstrated by the histoculture drug response assay. Anticancer Res 21:4083–4086PubMedGoogle Scholar
  6. 6.
    Singh B, Li R, Xu L, Poluri A, Patel S, Shaha AR, Pfister D, Sherman E, Hoffman RM, Shah J (2002) Prediction of survival in patients with head and neck cancer using the histoculture drug response assay. Head Neck 24:437–442CrossRefPubMedGoogle Scholar
  7. 7.
    Jung PS, Kim DY, Kim MB, Lee SW, Kim JH, Kim YM, Kim YT, Hoffman RM, Nam JH (2013) Progression-free survival is accurately predicted in patients treated with chemotherapy for epithelial ovarian cancer by the histoculture drug response assay in a prospective correlative clinical trial at a single institution. Anticancer Res 33:1029–1034PubMedGoogle Scholar
  8. 8.
    Freeman A, Hoffman RM (1986) In vivo-like growth of human tumors in vitro. Proc Natl Acad Sci U S A 83:2694–2698CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Vescio RA, Redfern CH, Nelson TJ, Ugoretz S, Stern PH, Hoffman RM (1987) In vivo-like drug response of human tumors growing in three-dimensional, gel-supported, primary culture. Proc Natl Acad Sci U S A 84:5029–5033CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ji WB, Um JW, Ryu JS, Hong KD, Kim JS, Min BW, Joung SY, Lee JH, Kim YS (2017) Clinical significance of 5-fluorouracil chemosensitivity testing in patients with colorectal cancer. Anticancer Res 37:2679–2682CrossRefPubMedGoogle Scholar
  11. 11.
    Geller J, Partido C, Sionit L, Youngkin T, Nachtsheim D, Espanol M, Tan Y, Hoffman RM (1997) Comparison of androgen-independent growth and androgen-dependent growth in BPH and cancer tissue from the same radical prostatectomies in sponge-gel matrix histoculture. Prostate 31:250–254CrossRefPubMedGoogle Scholar
  12. 12.
    Adlercreutz H, Markkanen H, Watanabe S (1993) Plasma concentrations of phyto-estrogens in Japanese men. Lancet 342:1209–1210CrossRefPubMedGoogle Scholar
  13. 13.
    Pavese JM, Krishna SN, Bergan RC (2014) Genistein inhibits human prostate cancer cell detachment, invasion, and metastasis. Am J Clin Nutr 100(Suppl 1):431S–436SCrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Peterson G, Barnes SL (1993) Genistein and biochanin A inhibit the growth of human prostate cancer cells but not epidermal growth factor receptor tyrosine autophosphorylation. Prostate 22:335–345CrossRefPubMedGoogle Scholar
  15. 15.
    Geller J, Sionit L, Partido C, Li L, Tan X-Y, Youngkin T, Nachtsheim D, Hoffman RM (1998) Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture. Prostate 34:75–79CrossRefPubMedGoogle Scholar
  16. 16.
    Shao TC, Tindall DJ, Cunningham GR (1986) Age dependency of androgen and estrogen effects on incorporation of (3H)thymidine by rat prostates in organ culture. Prostate 8:349–362CrossRefPubMedGoogle Scholar
  17. 17.
    de Boer W, Bolt J, Kuiper GG, Brinkmann AO, Mulder E (1987) Analysis of steroid- and DNA-binding domains of the calf uterine androgen receptor by limited proteolysis. J Ster Biochem 28:9–19CrossRefGoogle Scholar
  18. 18.
    Kennealey G, Furr B (1991) Use of the nonsteroidal anti-androgen casodex in advanced prostatic carcinoma. Urol Clin North Am 18:99–110PubMedGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.AntiCancer Inc.San DiegoUSA
  2. 2.Department of SurgeryUniversity of CaliforniaSan DiegoUSA

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