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Activity of cancer chemotherapeutic agents against human colorectal carcinomas grown as primary tissue culture

  • Original Papers
  • Experimental Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Summary

Improved procedures are described for the seeding of primary cultures from human colon adenocarcinoma and for the use of these cultures in the evaluation of drug effects. Two of the specimens studied were xenografts maintained in athymic (nude) mice, while the other six were biopsies obtained directly from patients. Tumor cells obtained directly from the patients proliferated in defined hormone-supplemented medium to the exclusion of other cells.

In drug-response studies with cultures from a colon tumor biopsy all four drugs studied (4′-deoxydoxorubicin, 4′-O-methyldoxorubicin, 5-fluorouracil, and 1,3-bis-[chloroethyl]-1-nitrosourea) inhibited growth of the cells within 3–6 days after drug treatment. On an equitoxic dose basis (LD10 in mice), 4′-deoxydoxorubicin appeared to be the most active drug. This drug also showed dose-dependent activity against one of the xenografted tumors in vitro. In dose-response studies with cultures from another patient's colon tumor, doxorubicin and 5-fluorouracil showed significant activity against the tumor 10 days after the drug treatment with concentrations at 1X and 10X average peak plasma levels.

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Abbreviations

DME:

Dulbecco's modification of Eagles's medium

F12:

Ham's F12 medium

CEM:

Chee's essential medium

FCS:

fetal calf serum

HS:

horse serum

EGF:

epidermal growth factor

MES:

2-(N-morpholino)ethanesulfonic acid

DX:

doxorubicin

deoDX:

4′-2-(N-morpholino)ethanesulfonic acid

O-DX:

4′-O-methyldoxorubicin

5-FU:

5-fluorouracil

BCNU:

1,3-bis-2-(chloroethyl)-1-nitrosourea

LD10 :

mg/kg of the drug producing 10% mortality in mice

ID50 :

μg/ml of the drug producing 50% inhibition of colonies

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Author notes

  1. Jurgen van der Bosch

    Present address: Forschungsinstitut Borstel, Institut für Experimentelle Biologie und Medizin, D-2061, Borstel, Federal Republic of Germany

  2. Hideo Masui

    Present address: Department of Medicine, Memorial Sloan-Kettering Cancer Center, 10021, New York, NY, USA

Authors and Affiliations

  1. Surgical Service, VA Medical Center, 07109, East Orange, NJ, USA

    Karimullah A. Zirvi, Jurgen van der Bosch, Hideo Masui, Nathan O. Kaplan & George J. Hill

  2. Department of Surgery, UMDNJ-New Jersey Medical School, 07103, Newark, NJ, USA

    Karimullah A. Zirvi, Jurgen van der Bosch, Hideo Masui, Nathan O. Kaplan & George J. Hill

Authors
  1. Karimullah A. Zirvi
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  2. Jurgen van der Bosch
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  3. Hideo Masui
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  4. Nathan O. Kaplan
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  5. George J. Hill
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Additional information

Deceased (4/86). Part of the work was done in Dr. Kaplan's laboratory at the Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA

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Zirvi, K.A., van der Bosch, J., Masui, H. et al. Activity of cancer chemotherapeutic agents against human colorectal carcinomas grown as primary tissue culture. J Cancer Res Clin Oncol 113, 20–26 (1987). https://doi.org/10.1007/BF00389962

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  • DOI: https://doi.org/10.1007/BF00389962

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