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  • 1
    Electronic Resource
    Electronic Resource
    Quantitative association between the in vitro human tumor stem cell assay and clinical response to cancer chemotherapy (1981)
    Springer
    Cancer chemotherapy and pharmacology 6 (1981), S. 211-218 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Objective methods have been developed to quantitate results of the in vitro human tumor stem cell assay, the degree of the association between the in vitro assay and clinical response as well as the likelihood of response. Methods considered to quantitate in vitro assay data included first-order kinetics of percent survival with drug concentration, minimal percent of tumor colony-forming unit survival at low drug concentrations, and area under the in vitro percent survival-drug concentration curve. Based upon experimental data, the percent tumor colony survival and the area under the curve (i.e., in vitro sensitivity indices) were concluded to better account than other methods for the commonly observed nonlinear shape of the in vitro curves. The two methods also yielded equivalent quantitative descriptions of the in vitro data. A logistic regression model was used for explicit quantitation of the relationship between the in vitro sensitivity index and predicted probability of clinical response. Very high association was observed between the predicted in vivo and actual clinical response for the cytotoxic drugs considered. Incorporation of other pharmacologic and patient prognostic factors into the quantitative methods is discussed and shown to improve their effectiveness.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00256973
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacologic studies of anticancer drugs with the human tumor stem cell assay (1981)
    Springer
    Cancer chemotherapy and pharmacology 6 (1981), S. 253-264 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To optimize the human tumor stem cell assay (HTSCA) for clinical and research purposes we have carried out in vitro pharmacology studies. Useful observations were made in four areas. (1) Drug assay design: The predictive accuracy of the HTSCA depends on the in vitro testing of drug concentrations of less than 10% of those which are pharmacologically achievable with standard in vivo drug doses. The use of unrealistically high in vitro concentrations can accurately predict clinical drug resistance, but is likely to yield high false-positive rates of clinical response prediction. (2) Drug scheduling: For certain schedule-dependent drugs, as well as those with a prolonged plasma half-life and those used according to a repeated daily schedule, prolonged in vitro exposure (rather than 1 h) may be needed to provide an adequate in vitro design. For an accurate prediction of sensitivity of tumor colony-forming units (TCFUs) to continuous drug contact in the agar, concentrations should be in the range of 1/300 that used for the standard 1-h exposure prior to plating. (3) Drug combinations: In preliminary studies of combination chemotherapy in vitro we commonly observed at least additive effects with low doses of cis-platinum plus either vinblastine or adriamycin. (4) Drug bioactivation: Rat liver microsomes or S-9 fraction were used to activate cyclophosphamide for in vitro effect, and satisfactory dose-response curves were observed for the inhibition of TCFUs. Such pharmacologic studies will be required for a wide variety of standard and new agents and will probably become a regular aspect of investigation of new anticancer drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00256978
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Chemotherapy of ovarian cancer directed by the human tumor stem cell assay (1981)
    Springer
    Cancer chemotherapy and pharmacology 6 (1981), S. 279-285 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The human tumor stem cell assay (HTSCA) has been used to study the in vitro sensitivity rates of anticancer drugs used in the treatment of 115 patients with previously untreated and relapsing ovarian cancer. The data from these studies have identified patterns of cross resistance and residual sensitivity between these agents, and have allowed the prospective selection of single agents possessing in vitro activity for the treatment of 32 patients with relapsing disease. cis-Platinum and vinblastine were the most active agents in vitro against ovarian TCFUs from both previously untreated and relapsing patients. Prior therapy with even one drug was associated with the acquisition of resistance to several classes of compounds (e.g., melphalan resistance was almost always associated with in vitro adriamycin resistance, P〉0.001). A clinical trial yielding similar data would have required nearly 450 evaluable ovarian cancer patients. In 11 of 32 patients in vitro testing predicted sensitivity to single agents: eight of these had partial remissions for a predictive accuracy of 73%. In 33 instances the HTSCA had 100% accuracy in predicting the lack of clinical response. Thus, the HTSCA for advanced ovarian cancer appears to have a similar predictive accuracy rate to the estrogen receptor assay for predicting the response to hormonal therapy for disseminated breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00256981
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Kinetics of clonogenic melanoma cell proliferation and the limits on growth within a bilayer agar system (1984)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 121 (1984), S. 114-124 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Accurate descriptions of the kinetics of cell growth in semi-solid agar clonogenic systems have been difficult because the number of cells in colonies of different sizes is largely unknown. We stained and removed tumor cell colonies from agar, directly counted their cells, and established equations to quantitate the number of cells within colonies of different sizes. We used these equations to quantitate, in terms of cell number and volume, the total amount and kinetics of clonogenic cell proliferation from biopsies of human melanoma and cell lines of several different tumor types. Daily observations of cells in agar and serial photography indicated a 0- to 4-day delay in the onset of proliferation in agar followed by rapid growth and then abrupt cessation of proliferation. We quantified the extent of proliferation of cells from melanoma biopsies of seven patients and 11 cell lines after they were allowed to proliferate in agar until they stopped. Approximately 10% of cells divided one to five times while only 0.01% divided six to nine times. The total number of cells within the colonies at the end of growth was different while the total volume of cells within the colonies per plate was similar; approximately 109 μm3 cellular volume per plate represents an upper limit for proliferation within the closed, nonrefed bilayer agar system. Previous replating studies using the same biopsy cells have shown that clonogenic melanoma cells can self-renew and have more proliferative capacity than that expressed during primary colony formation. Thus, the clonogenic assay only measured initial proliferative capacities. Furthermore, variable delays in the onset of proliferation may contribute to the heterogenity of colony size within clonogenic assays.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041210114
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    Paper (German National Licenses)
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