Advertisement

Direct Cloning of Human Ovarian Cancer in Soft Agar: Clinical Limitations and Pharmacologic Applications

  • R. F. Ozols
  • W. M. Hogan
  • R. C. Young
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 94)

Abstract

Epithelial ovarian cancer is a disease which is well suited to the evaluation of in vitro tests for the individual selection of a patient’s chemotherapy, since a variety of antineoplastic drugs have significant activity in this disease (Young 1975). A predictive in vitro test could therefore potentially identify those drugs active for a particular patient and thereby spare her the unnecessary toxic effects of inactive drugs. In addition, many patients with advanced ovarian cancer have malignant effusions (ascites or pleural fluid) which provide an easily accessible source of cells for in vitro analysis. Additional malignant cells can also be obtained frequently by peritoneal lavage from patients who do not have clinically evident ascites (Ozols et al. 1981). The observation (Hamburger et al. 1978) that human ovarian cancer cells can form tumor colonies in soft agar along with the promising preliminary results of in vitro/in vivo correlations of drug resistance using this assay (Salmon et al. 1978; Alberts et al. 1980) led to our study on the growth of ovarian cancer tumor colonies from peritoneal washings as well as malignant effusions (Ozols et al. 1980a). In addition to evaluating the assays’ potential for individualization of chemotherapy, we have also used the human tumor stem cell assay (HTSCA) to investigate patterns of drug resistance and cross-resistance in ovarian cancer. In this report we will summarize our results with 215 ovarian cancer specimens, which demonstrate that, while the HTSCA has major limitations for the individualization of chemotherapy, the patterns of drug resistance and cross-resistance have provided clinically relevant information for the design of novel therapeutic approaches in ovarian cancer, such as intraperitoneal chemotherapy and high-dose cisplatin.

Keywords

Ovarian Cancer Epithelial Ovarian Cancer Soft Agar Ovarian Cancer Patient Human Ovarian Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alberts DS, Chen HSG, Soehnlen B et al. (1980) In vitro clonogenic assay for predicting response of ovarian cancer to chemotherapy. Lancet 2: 340–342PubMedCrossRefGoogle Scholar
  2. Hamburger AW, Salmon SE, Kim MB, Trent JM, Soehnlen BJ, Alberts DS, Smith HJ (1978) Direct cloning of human ovarian cancer cells in agar. Cancer Res 38: 3438–3444PubMedGoogle Scholar
  3. Hamilton TC, Foster BJ, Grotzinger KR et al. (1983) Development of drug sensitive and resistant human ovarian cancer cell lines: a model system for indentifying new drugs and procedures. Proc Am Assoc Cancer Res 24: 313Google Scholar
  4. Hogan WM, Young RC (1982) Gynecologic malignancies. Cancer Chemotherapy 1982. Excerpta Medica, Amsterdam, pp 309–339Google Scholar
  5. Hogan WM, Ozols RF, Willson JFV et al. (1982) Application of the human tumor stem cell assay to the study of epithelial ovarian cancer. (Abstract). Presented at Society of Gynecology and OncologyGoogle Scholar
  6. Litterst CL (1981) Alterations in the toxicity of cis-dichlorodiammine platinum and in tissue localization as a function of NaC1 concentrations in the vehicle of administration. Toxicol Appl Pharmacol 61: 99–108PubMedCrossRefGoogle Scholar
  7. Ozols RF, Young RC (1983) Phase II trial of high dose cisplatin in refractory ovarian cancer patients. Medicine Branch, NCIGoogle Scholar
  8. Ozols RF, Willson JKV, Grotzinger KR, Young RC (1980) Cloning of human ovarian cancer cells in soft agar from malignant effusions and peritoneal washings. Cancer Res 40: 2743–2747PubMedGoogle Scholar
  9. Ozols RF, Wilson JKV, Weitz MD, Grotzinger KR, Myers CE, Young RC (1980b) Inhibition of human ovarian cancer colony formation by Adriamycin and its major metabolites. Cancer Res 40: 4109–4112PubMedGoogle Scholar
  10. Ozols RF, Fisher RI, Anderson T et al. (1981) Peritoneoscopy in the management of ovarian cancer. Am J Obstet Gynecol 140: 611–619PubMedGoogle Scholar
  11. Ozols RF, Young RC, Speyer JL et al. (1982) Phase I and pharmacologic studies of Adriamycin administered intraperitoneally to patients with ovarian cancer. Cancer Res 42: 4265–4269PubMedGoogle Scholar
  12. Ozols RF, Corden BJ, Jacob J et aI. (1984) High-dose cisplatin in hypertonic saline. Ann Int Med 100: 19–24Google Scholar
  13. Salmon SE, Buick RN (1979) Preparation of permanent slides of intact soft-agar colony cultures of hematopoietic and tunor stem cells. Cancer Res 39: 1133–1136PubMedGoogle Scholar
  14. Salmon SE, Hamburger AW, Soehnlen B, Durie BGM, Alberts DS, Moon TE (1978) Quantitation of differential sensitivity of human tumor stem cells to anticancer drugs. N Eng J Med 298: 1321–1327CrossRefGoogle Scholar
  15. Von Hoff DD, Casper J, Bradley E et al. (1981) Association between human tumor colony forming assay results and response of an individual patient’s tumor to chemotherapy. Am J Med 70: 1027–1032CrossRefGoogle Scholar
  16. Von Hoff DD, Clark GM, Stogdill BJ, et al. (1983) Prospective clinical trial of a human tumor cloning system. Cancer Res 43: 1926–1931Google Scholar
  17. Young RC (1975) Chemotherapy of ovarian cancer: past and present. Semin Oncol 2: 267–27PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1984

Authors and Affiliations

  • R. F. Ozols
    • 1
  • W. M. Hogan
    • 1
  • R. C. Young
    • 1
  1. 1.Department of Health and Human Services, Public Health ServiceNational Institutes of HealthBethesdaUSA

Personalised recommendations