HISTOCULTURE DRUG RESPONSE ASSAY - HDRA^®  

CLINICAL BENEFITS OF USING THE HISTOCULTURE DRUG RESPONSE ASSAY (HDRA)

Except from the Human Tumor Assay Journal by Larry Weisenthal, MD, PhD, at “weisenthal.org”:

 

“…patients are 7 times more likely to benefit from treatment with CCDRT (cell culture drug resistance testing) active drugs than from treatment with CCDRT inactive drugs, in scores of studies, involving thousands of patients.”

Histoculture Drug Response Assay - FEATURES

	Three dimensional culture
	Indivudualized cancer patient tumor sensitivity
	Drug discovery
	Prostate androgen sensitivity assay
	High correlation to clinical drug sensitivity
	The HDRA determines both drug sensitivity and resistance

APPLICATIONS OF THE HISTOCULTURE DRUG RESPONSE ASSAY

	Determination of Best Treatment Options For Individual Patients for all Solid Tumor Types
	Determination of Optimal Treatment for Tumors Without Standard Therapy
	Screening of Compound Libraries for Activity on Real Human Tumors

HOW TO USE HDRA^® BY ONCOLOGISTS AND PATIENTS

	Telephone 858-654-2555, 800-511-2555 to have tumor transport pack sent to you.
	Send fresh tumor specimen in tube provided in transport pack.
	Indicate tumor type and drugs to be tested on form provided in transport pack.
	Send transport pack by FedEx to AntiCancer, Inc. at 7917 Ostrow St., San Diego, CA 92111.
	Chemosensitivity report will be sent by Fax/Email within 7 days.

TO VIEW WHOLE HDRA PRESENTATION CLICK HERE: 

HDRA Protocol

Specimen is received in transport medium	Tumor is minced	Tumor fragments are placed in histoculture	Tumor fragments are treated with drugs. MTT is added. Resistant cells are stained, sensitive cells do not stain.

 MTT stain is extracted from each tumor fragment and quantified in a plate reader

HDRA CHEMOSENSITIVITY REPORTS 

(TYPICAL EXAMPLES)

Inhibition rate indicates drug efficacy; the higher the rate the more effective the drug. 

High correlation of gastric-cancer patient survival with Histoculture Drug Response Assay (HDRA^®).

Kaplan-Meir patient survival curves.Gastric cancer patients were treated with Mitomycin C. Group A consisted of 10 patients whose tumors were sensitive to Mitomycin C in vitro, group B consisted of 22 patients whose tumors were insensitive to Mitomycin C in vitro. See Furukawa, T., Kubota, T., Hoffman, R.M.  Clinical applications of the histoculture drug response assay.  See Clinical Cancer Research 1, 305-311, 1995 for details. 

                                   High correlation of head-and-neck-cancer patient survival with Histoculture Drug Response Assay (HDRA^®).

Cause-specific survival by multidrug resistance based on the histoculture drug response assay. Multidrug resistance was defined as in vitro resistance to both cisplatin and 5-fluoracil. Survival comparisons were performed using the Wilcoxon test (p=.01). See Head Neck 24, 437-442, 2002 for details. (For abstract of the paper refer to:)

HDRA^® PATENTS

US 5,474,909   US 5,726,009

HDRA^® BIBLIOGRAPHY

1.             Freeman, A., and Hoffman, R.M.  In vivo-like growth of human tumors in vitro.  Proc. Natl. Acad. Sci. USA 83, 2694-2698, 1986.

2.             Vescio, R.A., Redfern, C.H., Nelson, T.J., Ugoretz, S., Stern, P.H., and Hoffman, R.M.  In vivo-like drug response of human tumors growing in three-dimensional, gel-supported, primary culture.  Proc. Natl. Acad. Sci. USA 84, 5029-5033, 1987.

3.             Hoffman, R.M., Monosov, A.Z., Connors, K.M., Herrera, H., and 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. USA 86, 2013-2017, 1989.

4.             Wallen, J.W., Cate, R.L., Kiefer, D.M., Riemen, M.W., Martinez, D., Hoffman, R.M., Donahoe, P.K., Von Hoff, D.D., Pepinsky, B., and A. Oliff.  Minimal antiproliferative effect of recombinant Mullerian Inhibiting Substance on gynecological tumor cell lines and tumor explants.  Cancer Res. 49, 2005-2011, 1989.

5.             Vescio, R.A., Connors, K.M., Youngkin, T., Bordin, G.M., Robb, J.A., Umbreit, J.N., and Hoffman, R.M.  Cancer biology for individualized cancer therapy: Correlation of growth fraction index in native-state culture with tumor grade and stage.  Proc. Natl. Acad. Sci. USA 87, 691-695, 1990.

6.             Vescio, R.A., Connors, K.M., Bordin, G.M., Robb, J.A., Youngkin, T., Umbreit, J.N., and Hoffman, R.M.  The distinction of small cell and non-small cell cancer by growth in native-state histoculture.  Cancer Res. 50, 6095-6099, 1990.

7.             Robbins, K.T., Varki, N.M., Storniolo, A.M., Hoffman, H., and Hoffman, R.M.  Drug response of head and neck tumors in native-state histoculture.  Archives of Otolaryngology Head and Neck Surg. 117, 83-86, 1991.

8.             Hoffman, R.M.  Three-dimensional gel-supported native-state histoculture for evaluation of tumor-specific pharmacological activity: Principles, practices and possibilities.  J. Cell. Pharmacol. 2, 189-201, 1991.

9.             Li, L., Hoffman, R.M.  Eye tissues grown in 3-dimensional histoculture for toxicological studies.  J. Cell.  Pharmacol. 2, 311-316, 1991.

10.          Hoffman, R.M.  Three-dimensional histoculture: Origins and applications in cancer research.  Cancer Cells 3, 86-92, 1991.

11.          Hoffman, R.M.  In vitro sensitivity assays in cancer: A review, analysis and prognosis.  J. Clin. Lab. Anal. 5, 133-143, 1991.

12.         Vescio, R.A., Connors, K.M., Kubota, T., and Hoffman, R.M.  Correlation of histology and drug response of human tumors grown in native-state three-dimensional histoculture and in nude mice. Proc. Natl. Acad. Sci. USA 88, 5163-5166, 1991.

13.          Guadagni, F., Roselli, M., and Hoffman, R.M.  Maintenance of expression of tumor antigens in three-dimensional in vitro human tumor gel-supported histoculture.  Anticancer Res. 11, 543-546, 1991.

14.      Baibakov, B., Frank, G.A., Sergeeve, N., Youngkin, T., Connors, K.M., Hoffman, R.M., and Margolis, L.B.  In vivo growth patterns of human lung tumors in three-dimensional histoculture.  In Vitro Cell. Dev. Biol. 27A, 897-899, 1991.

15.      Furukawa, T., Kubota, T., Watanabe, M., Takahara, T., Yamaguchi, H., Takeuchi, T., Kase, S., Kodaira, S., Ishibiki, K., Kitajima, M., and Hoffman, R.M.  High in vitro-in vivo correlation of drug response using sponge-gel-supported three-dimensional histoculture and the MTT end point.  Int. J. Cancer 51, 489-498, 1992.

16.      Guo, H.Y., Colangelo, D., Li, L., Connors, K.M., Kubota, T., and Hoffman, R.M.  In vitro histoculture of human tumors with fluorescent dye end-points measured by confocal microscopy: high correlation of in vitro and in vivo chemosensitivity.  Anticancer Research 12, 1055-1062, 1992.

17.       Guadagni, F., Li, L., and Hoffman, R.M.  Targeting antibodies to live tumor tissue in 3-D histoculture.  In Vitro Cell. Dev. Biol. 28A, 297-299, 1992.

18.      Colangelo, D, Guo, H-Y, Silvestro, L., and Hoffman, R.M.  Noncolorimetric measurement of cell activity in three-dimensional histoculture using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide: the pixel image analysis of formazan crystals.  Anal. Biochem. 205, 8-13, 1992.

19.       Slocum, H.K., Toth, K. Li, L., Chang, S.G, Hoffman, R.M., and Rustum, Y.M.  Long-term passage of human tissues in vitro as three-dimensional histolines.  In Vitro Cell. Dev. Biol. 28A, 573-577, 1992.

20.         Colangelo, D., Guo, Y.H., Connors, K.M., Kubota, T., Silvestro, L., and Hoffman, R.M.  Correlation of drug response in human tumors histocultured in vitro with an image-analysis MTT end point and in vivo xenografted in nude mice. Anticancer Res. 12, 1373-1376, 1992.

21.         Geller, J., Sionit, L.R., Connors, K.M., and Hoffman, R.M.  Measurement of androgen sensitivity in the human prostate in in vitro three-dimensional histoculture.  The Prostate 21, 269-278, 1992.

22.         Chang, S.G., Slocum, H., Toth, K., Hoffman, R.M., Perrapato, S.D., Huben, R.P., and Rustum, Y.M.  Glucose consumption end point in primary histoculture indicates recovery of human tumors from drug treatment.  In Vitro Cell. Dev. Biol. 28A, 585-587, 1992.

23.      Hoffman, R.M.  Histoculture and the immunodeficient mouse come to the cancer clinic: Rational approaches to individualizing cancer therapy and new drug evaluation (Review).  International Journal of Oncology 1, 467-474, 1992.

24.      Hoffman, R.M.  To do tissue culture in two or three dimensions?  That is the question.  Stem Cells 11, 105-111, 1993.

25.         Theodorescu, D., Connors, K.M., Groce, A., Hoffman, R.M., and Kerbel, R.S.   Lack of influence of c-Ha-ras expression on the drug sensitivity of human bladder cancer histocultured in three dimensions.  Anticancer Res. 13, 941-946, 1993.

26.         Hoffman, R.M.  In vitro assays for chemotherapy sensitivity.   Crit. Rev. in Onc/Hem. 15, 99-111, 1993.

27.         Geller, J., Sionit, L.R., Connors, K.M., Youngkin, T., and Hoffman, R.M.  Expression of prostate-specific antigen in human prostate specimens in in vitro three dimensional histoculture.  In Vitro Cell. Dev. Biol. 29A, 523-524, 1993.

28.         Chang, S.G., Chai, S.O., Kim, E.S, Yoon, C., Joo, H.Z., and Hoffman, R.M.  The measurement of glucose consumption in histoculture to determine effects of doxorubicin and cisplatinum on human gastric carcinoma. Anticancer Res. 13, 1303-1310, 1993.

29.         Tanino, H., Kubota T., Saikawa, Y., Kuo, T-H., Takeuchi, T., Kase, S., Kurukawa, T., Kitajima, M. Saurai, T., Naito, Y. and Hoffman, R.M.  Different chemo- and endocrino-sensitivity of MCF‑7 cells with or without estradiol supplement in vitro. Anticancer Res. 13, 1219-1222, 1993.

30.         Robbins, T., Connors, K.M., Storniolo, A.M., Hanchett, C., and Hoffman, R.M.  Sponge-gel supported histoculture drug-response assay for head and neck cancer: Correlations with clinical response to cisplatin.  Arch. Otol. Head & Neck Surg. 120, 288-292, 1994.

31.         Chang, S.G., Lee, J.H., Hong, D.H., Lee, H.Y., Chai, S.E. and Hoffman, R.M.  Comparison of glucose-consumption and thymidine-incorporation endpoints on histocultured human superficial bladder tumor.  Anticancer Res. 14, 77-83, 1994.

32.         Hoffman, R.M.  The three-dimensional question: can clinically relevant tumor drug resistance be measured in vitro? Cancer and Metastasis Reviews 13, 169-173, 1994.

33.         Geller, J., Sionit, L.R., Baird, A., Kohls, M., Connors, K.M., and Hoffman, R.M.  In vivo and in vitro effects of androgen on FGF-2 concentrations in the human prostate.  The Prostate 25, 206-209, 1994.

34.         Furukawa, T., Kubota, T., Hoffman, R.M.  Clinical applications of the histoculture drug response assay.  Clinical Cancer Research 1, 305-311, 1995.

35.         Kubota, T., Sasano, N., Abe, O., Nakao, I., Kawamura, E., Saito, T., Endo, M., Kimura, K., Demura, H., Sasano, H., Nagura, H., Ogawa, N., and Hoffman, R.M.  Potential of the histoculture drug response assay to contribute to cancer patient survival.  Clinical Cancer Research 1, 1537-1543, 1995.

36.         Hoffman, R.M.  In vitro drug response assays for entry into the rational era cancer chemotherapy.  Human Cell 8, Japan Human Cell Society, 131-148, 1995.

37.          Hoffman, R.M.  Can in vitro drug response assays be clinically useful?  Problems and solutions.  Biotherapy 10, 822-842, 1996.

38.         Chang, S-G., Jung, J-C., Rho, Y-S., Huh, J-S., Kim, J-I., and Hoffman, R.M.  Efficacy of the platinum analog {Pt(cis-dach)(DPPE) - 2NO₃} on histocultured human patient bladder tumors and cancer cell lines.  Anticancer Res. 16, 3423-3428, 1996.

39.          Chang, S-G., Lee, S.J., Lee, S-J., Kim, J.I., Jung, J-C. and Hoffman, R.M.  Interleukin-6 production in primary histoculture by normal human kidney and renal tumors tissues.  Anticancer Res. 17, 113-116, 1997.

40.       \Geller, J., Partido, C., Sionit, L., Youngkin, T., Espanol, M., Tan, Y., and Hoffman, R.M.  Comparison of androgen-independent growth and androgen-dependent growth in BPH and cancer tissue from the same radical prostatectomies in sponge-gel matrix histoculture.  The Prostate 31, 250-254, 1997.

41.         Hoffman, R.M.   Taking  chemotherapy  from random  to rational  with  the  histoculture drug response  assay.  Jpn. J. Cancer Chemother. 24, 206-229, 1997.

42.         Chishima, T., Yang, M., Miyagi, Y., Li, L., Tan, Y., Baranov, E., Shimada, H., Moossa, A.R., Penman, S., and Hoffman, R.M.  Governing step of metastasis visualized in vitro.  Proc. Natl. Acad. Sci. USA 94, 11573-11576, 1997.

43.         Chishima, T., Miyagi, Y., Li, L., Tan, Y., Baranov, E., Yang, M., Shimada, H., Moossa, A.R., and Hoffman, R.M. The use of histoculture and green fluorescent protein to visualize tumor cell host interaction.  In Vitro Cell. Dev. Biol. 33, 745-747, 1997.

44.         Geller, J., Sionit, L., Partido, C., Li, L., Tan, X-Y., Youngkin, T., Nachtsheim, D., and Hoffman, R.M.  Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture.  The Prostate 34, 75-79, 1998

45.         Hoffman, R.M.  Three-dimensional sponge-gel matrix histoculture of human tumors:  Methods and applications. In: Cell Biology, A Laboratory Handbook 1, 367-379, Ed: J. Celis, San Diego: Academic Press, 1994.

46.         Hoffman, R.M.  Three-dimensional sponge-gel matrix histoculture of human tumors:  Methods and applications. In: Cell Biology, A Laboratory Handbook 2(1), 377-389, Ed: J. Celis, San Diego: Academic Press, 1998.

47.         Olbina, G., Miljkovic, D., Hoffman, R.M., and Geller, J.  New sensitive discovery histoculture model for growth-inhibition studies in prostate cancer and BPH.  The Prostate 37, 126-129, 1998.

48.         Haran, C.  Custom chemo.  MAMM, 49-53, September/October 1999.

49.         Hoffman, R.M.  The clinical benefit of the histoculture drug response assay.  Jpn. J. Cancer Chemother 27, Supplement 11, 321-322, 2000.

50.         Ohie, S., Udagawa, Y., Kozu, A., Komuro, Y., Aoki, D., Nozawa, S., Moossa, A.R., and Hoffman, R.M. Cisplatin sensitivity of ovarian cancer in the histoculture drug response assay correlates to clinical response to combination chemotherapy with cisplatin, doxorubicin, and cyclophosphamide. Anticancer Research 20, 2049-2054, 2000.

51.         Furukawa, T., Kubota, T., Tanino, H., Oura, S., Yuasa, S., Murate, H., Morita, K., Kozakai, K., Yano, T., and Hoffman, R.M.  Chemosensitivity of breast cancer lymph node metastasis compared to the primary tumor from individual patients tested in the histoculture drug response assay.  Anticancer Research 20, 3657-3658, 2000.

52.         Hoffman, R.M.  Histocultures and Organ Cultures. In: Encyclopedia of Life Sciences, http://www.els.net/, London: Nature Publishing Group, 2001.

53.      Tanino, H., Oura, S., Hoffman, R.M., Kubota, T., Furukawa, T., Arimoto, J., Yoshimasu, T., Hirai, I., Bessho, T., Suzuma, T., Sakuari, T., and Naito, Y. Acqusition of multidrug resistance in recurrent breast cancer demostrated by the histoculture drug response assay. Anticancer Res. 21, 4083-4086, 2001.

54.      Singh, B., Li, R., Xu, L., Poluri, A., Patel, S., Shaha, A. S., Pfister, D., Sherman, E., Goberdhan, A., Hoffman, R. M., Shah, J.Prediction of survival in patients with head and neck cancer using the histoculture drug response assay. 24, Head&Neck. 437-442, 2002.

55.      Flowers, JL., Hoffman, R.M., Driscoll, T.A., Wall, M.E., Wani, M.C., Manikumar, G., Friedman, H.S., Dewhirst, M., Colvin, O.M., Adams, D.J. The activity of camptothecin analogues is enhanced in histocultures of human tumors and human tumor xenografts by modulation of extracellular pH. Cancer Chemotherapy and Pharmacology 52, 253-261, 2003.