An in vitro tetrazolium dye (MTT) reduction technique was modified and evaluated for use in the large-scale screening of anticancer compounds by examining the activity of ten clinically used drugs against 16 different human and murine cell populations. Cell populations included colon and mammary adenocarcinomas, melanomas, leukemias, and freshly isolated normal cells. Cell lines were grown in microtiter plates for 18-20 hours prior to a 72-hour continuous exposure to the drugs. Cultures were initiated at cell densities which maximized both the difference in dye reduction and the number of cell doublings between the beginning and end of the drug exposure period. Drug potency, expressed as the 50% inhibitory concentration (IC50), was comparable whether the effect on cell doublings or dye reduction was determined. There was good agreement between this method and the more labor-intensive, conventional method of counting trypan blue dye-excluding cells in a hemacytometer. Implemented as a large-scale, high-capacity system, our adaptation of the MTT technique is a rapid, sensitive, reproducible first-line screening device for detecting anticancer compounds with cytostatic or cytocidal activity.
{"title":"Semiautomated colorimetric assay for in vitro screening of anticancer compounds.","authors":"R L Ruben, R H Neubauer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>An in vitro tetrazolium dye (MTT) reduction technique was modified and evaluated for use in the large-scale screening of anticancer compounds by examining the activity of ten clinically used drugs against 16 different human and murine cell populations. Cell populations included colon and mammary adenocarcinomas, melanomas, leukemias, and freshly isolated normal cells. Cell lines were grown in microtiter plates for 18-20 hours prior to a 72-hour continuous exposure to the drugs. Cultures were initiated at cell densities which maximized both the difference in dye reduction and the number of cell doublings between the beginning and end of the drug exposure period. Drug potency, expressed as the 50% inhibitory concentration (IC50), was comparable whether the effect on cell doublings or dye reduction was determined. There was good agreement between this method and the more labor-intensive, conventional method of counting trypan blue dye-excluding cells in a hemacytometer. Implemented as a large-scale, high-capacity system, our adaptation of the MTT technique is a rapid, sensitive, reproducible first-line screening device for detecting anticancer compounds with cytostatic or cytocidal activity.</p>","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14809708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phase I trial of N-methylformamide in pediatric patients with refractory leukemias.","authors":"S B Murphy, J Mirro, C H Pui, C B Pratt","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14810302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J H Saiers, B Blumenstein, M Slavik, J H Costanzi, E D Crawford
{"title":"Phase II study of spirogermanium in advanced adenocarcinoma of the prostate: a Southwest Oncology Group Study.","authors":"J H Saiers, B Blumenstein, M Slavik, J H Costanzi, E D Crawford","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14810305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multiple drug intensification after cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) induction in metastatic breast cancer: a Southeastern Cancer Study Group phase II trial.","authors":"C L Vogel, M Raney, J Carpenter","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14810444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G B Weiss, B Metch, D D Von Hoff, S A Taylor, J H Saiers
{"title":"Phase II trial of fludarabine phosphate in patients with head and neck cancer: a Southwest Oncology Group Study.","authors":"G B Weiss, B Metch, D D Von Hoff, S A Taylor, J H Saiers","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13593975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J L Grem, D F Hoth, J M Hamilton, S A King, B Leyland-Jones
{"title":"Overview of current status and future direction of clinical trials with 5-fluorouracil in combination with folinic acid.","authors":"J L Grem, D F Hoth, J M Hamilton, S A King, B Leyland-Jones","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14445205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W G Jones, S D Fosså, A V Bono, J G Klijn, M De Pauw, R Sylvester
{"title":"European Organization for Research and Treatment of Cancer (EORTC) phase II study of low-dose weekly epirubicin in metastatic prostate cancer.","authors":"W G Jones, S D Fosså, A V Bono, J G Klijn, M De Pauw, R Sylvester","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14603917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cyclophosphamide hypersensitivity and cross-reactivity with chlorambucil.","authors":"L Kritharides, K Lawrie, G A Varigos","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14623003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L Beex, J Burghouts, J van Turnhout, W Breed, H Hillen, A Holdrinet, G Boetius, G Hoogendoorn, W Doesburg, M Verhulst
In a multicenter trial, 123 patients with advanced breast cancer who had been treated with tamoxifen and/or chemotherapy were randomized to receive medroxyprogesterone acetate (MPA) orally 300 mg X 3 daily or im 500 mg daily for 4 weeks and 500 mg X 2 weekly thereafter. All case histories were reviewed extramurally by the criteria of the International Union Against Cancer. Five and 11 patients were not eligible and evaluable for response, respectively. Pretreatment characteristics were well balanced in both treated groups. Twenty-five of all 107 (23%) evaluable patients achieved an objective remission, whereas in a further 15% the disease became stable after previous progression. Results in both treatment arms did not differ significantly. The median duration of objective remission was 12 and 14 months for orally and im treated patients, respectively (P greater than 0.10). No statistically significant differences in the survival times of orally and im treated patients were found. Pretreatment characteristics positively correlated with an objective remission during MPA therapy in both groups were age greater than 50 years (P less than 0.02) and no previous chemotherapy (P less than 0.01). Toxicity included an increase in body weight, cushingoid effects, muscle cramps, and tremors in both groups. In four patients on im therapy, local infections developed. Mean serum MPA levels reached values above 100 ng/ml in nine orally and eight im treated patients (P greater than 0.10), and neither differed significantly in the patients responding to or failing therapy. In both MPA arms, plasma cortisol levels were suppressed. The drop in plasma cortisol levels was more pronounced in patients with objective remissions than in patients who failed (P = 0.04). In conclusion, oral and im MPA in the given doses had similar activity. Im administration of MPA should be reserved for patients not able to take oral medication.
{"title":"Oral versus im administration of high-dose medroxyprogesterone acetate in pretreated patients with advanced breast cancer.","authors":"L Beex, J Burghouts, J van Turnhout, W Breed, H Hillen, A Holdrinet, G Boetius, G Hoogendoorn, W Doesburg, M Verhulst","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In a multicenter trial, 123 patients with advanced breast cancer who had been treated with tamoxifen and/or chemotherapy were randomized to receive medroxyprogesterone acetate (MPA) orally 300 mg X 3 daily or im 500 mg daily for 4 weeks and 500 mg X 2 weekly thereafter. All case histories were reviewed extramurally by the criteria of the International Union Against Cancer. Five and 11 patients were not eligible and evaluable for response, respectively. Pretreatment characteristics were well balanced in both treated groups. Twenty-five of all 107 (23%) evaluable patients achieved an objective remission, whereas in a further 15% the disease became stable after previous progression. Results in both treatment arms did not differ significantly. The median duration of objective remission was 12 and 14 months for orally and im treated patients, respectively (P greater than 0.10). No statistically significant differences in the survival times of orally and im treated patients were found. Pretreatment characteristics positively correlated with an objective remission during MPA therapy in both groups were age greater than 50 years (P less than 0.02) and no previous chemotherapy (P less than 0.01). Toxicity included an increase in body weight, cushingoid effects, muscle cramps, and tremors in both groups. In four patients on im therapy, local infections developed. Mean serum MPA levels reached values above 100 ng/ml in nine orally and eight im treated patients (P greater than 0.10), and neither differed significantly in the patients responding to or failing therapy. In both MPA arms, plasma cortisol levels were suppressed. The drop in plasma cortisol levels was more pronounced in patients with objective remissions than in patients who failed (P = 0.04). In conclusion, oral and im MPA in the given doses had similar activity. Im administration of MPA should be reserved for patients not able to take oral medication.</p>","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14809709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N Oishi, J Berenberg, B A Blumenstein, K Johnson, S E Rivkin, R M Bukowski, R M O'Bryan, R L Stephens, J Quagliana, J H Saiers
{"title":"Teniposide in metastatic renal and bladder cancer: a Southwest Oncology Group Study.","authors":"N Oishi, J Berenberg, B A Blumenstein, K Johnson, S E Rivkin, R M Bukowski, R M O'Bryan, R L Stephens, J Quagliana, J H Saiers","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9581,"journal":{"name":"Cancer treatment reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1987-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14810306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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