In vitro chemosensitivities of human tumor stem cells to the phase II drug 4'-(9-acridinylamino)methanesulfon-m-anisidide and prospective in vivo correlations

Frederick R Ahmann, F. L. Meyskens, T. E. Moon, B. G. Durie, S. E. Salmon

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Abstract

A potential application of the human tumor stem cell colony assay is to guide Phase II clinical investigations by identifying classes of tumors (or individual patients) which are sensitive in vitro to a new antitumor compound. We have tested human tumor stem cells from 140 tumor biopsies representing 20 different tumor types for chemosensitivity to the Phase II drug 4'-(9-acridinylamino)methanesulfon-m-anisidide. In vitro sensitivity was defined as a reduction in the number of tumor colony-forming cells to 30% of the control or less after a 1-hr exposure to one-tenth of the pharmacologically achievable plasma concentration of 4'-(9-acridinylamino)methanesulfon-m-anisidide. In vitro sensitivity was found in 29 cases: non-Hodgkin's lymphoma (2 of 2); cervical carcinoma (1 of 1); sarcoma (3 of 6); neuroblastoma (1 of 2); acute myelogenous leukemia (6 of 16); chronic myelogenous leukemia (1 of 3); melanoma (8 of 34); uterine carcinoma (1 of 5); lung carcinoma (1 of 9); ovarian carcinoma (4 of 36); and breast carcinoma (1 of 11). Prospective in vitro-in vivo correlations in eight patients with various tumor types showed that three of three patients sensitive in vitro to 4'-(9-acridinylamino)methanesulfon-m-anisidide responded in vivo, while five of five patients resistant in vitro had no clinical response. The results provide support for further evaluation of the utility of the human tumor stem cell colony assay for targeting Phase II clinical trials.

Original languageEnglish (US)
Pages (from-to)4495-4498
Number of pages4
JournalCancer Research
Volume42
Issue number11
StatePublished - 1982

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Neoplastic Stem Cells
Tumor Stem Cell Assay
Pharmaceutical Preparations
Carcinoma
Neoplasms
Phase II Clinical Trials
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neuroblastoma
Acute Myeloid Leukemia
Sarcoma
Non-Hodgkin's Lymphoma
In Vitro Techniques
Melanoma
Breast Neoplasms
Biopsy
Lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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In vitro chemosensitivities of human tumor stem cells to the phase II drug 4'-(9-acridinylamino)methanesulfon-m-anisidide and prospective in vivo correlations. / Ahmann, Frederick R; Meyskens, F. L.; Moon, T. E.; Durie, B. G.; Salmon, S. E.

In: Cancer Research, Vol. 42, No. 11, 1982, p. 4495-4498.

Research output: Contribution to journalArticle

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abstract = "A potential application of the human tumor stem cell colony assay is to guide Phase II clinical investigations by identifying classes of tumors (or individual patients) which are sensitive in vitro to a new antitumor compound. We have tested human tumor stem cells from 140 tumor biopsies representing 20 different tumor types for chemosensitivity to the Phase II drug 4'-(9-acridinylamino)methanesulfon-m-anisidide. In vitro sensitivity was defined as a reduction in the number of tumor colony-forming cells to 30{\%} of the control or less after a 1-hr exposure to one-tenth of the pharmacologically achievable plasma concentration of 4'-(9-acridinylamino)methanesulfon-m-anisidide. In vitro sensitivity was found in 29 cases: non-Hodgkin's lymphoma (2 of 2); cervical carcinoma (1 of 1); sarcoma (3 of 6); neuroblastoma (1 of 2); acute myelogenous leukemia (6 of 16); chronic myelogenous leukemia (1 of 3); melanoma (8 of 34); uterine carcinoma (1 of 5); lung carcinoma (1 of 9); ovarian carcinoma (4 of 36); and breast carcinoma (1 of 11). Prospective in vitro-in vivo correlations in eight patients with various tumor types showed that three of three patients sensitive in vitro to 4'-(9-acridinylamino)methanesulfon-m-anisidide responded in vivo, while five of five patients resistant in vitro had no clinical response. The results provide support for further evaluation of the utility of the human tumor stem cell colony assay for targeting Phase II clinical trials.",
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