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Research Article| Volume 98, ISSUE 3, P360-368, September 2005

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Conservation of in vitro drug resistance patterns in epithelial ovarian carcinoma

  • Author Footnotes
    1 Contributed equally to the preparation of this manuscript.
    Krishnansu S. Tewari
    Footnotes
    1 Contributed equally to the preparation of this manuscript.
    Affiliations
    The Division of Gynecologic Oncology, The Chao Family Comprehensive Cancer Center, University of California, Irvine-Medical Center, 101 The City Drive, Orange, CA 92868, USA
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  • Author Footnotes
    1 Contributed equally to the preparation of this manuscript.
    Rita S. Mehta
    Footnotes
    1 Contributed equally to the preparation of this manuscript.
    Affiliations
    The Section of Hematology & Oncology, The Chao Family Comprehensive Cancer Center, University of California, Irvine-Medical Center, 101 The City Drive, Orange, CA 92868, USA

    Oncotech, Inc., 15501 Red Hill Avenue, Tustin, CA 92780, USA
    Search for articles by this author
  • Robert A. Burger
    Affiliations
    The Division of Gynecologic Oncology, The Chao Family Comprehensive Cancer Center, University of California, Irvine-Medical Center, 101 The City Drive, Orange, CA 92868, USA
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  • Ing-Ru Yu
    Affiliations
    Oncotech, Inc., 15501 Red Hill Avenue, Tustin, CA 92780, USA
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  • Ainura S. Kyshtoobayeva
    Affiliations
    Oncotech, Inc., 15501 Red Hill Avenue, Tustin, CA 92780, USA
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  • Bradley J. Monk
    Affiliations
    The Division of Gynecologic Oncology, The Chao Family Comprehensive Cancer Center, University of California, Irvine-Medical Center, 101 The City Drive, Orange, CA 92868, USA
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  • Alberto Manetta
    Affiliations
    The Division of Gynecologic Oncology, The Chao Family Comprehensive Cancer Center, University of California, Irvine-Medical Center, 101 The City Drive, Orange, CA 92868, USA
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  • Michael L. Berman
    Affiliations
    The Division of Gynecologic Oncology, The Chao Family Comprehensive Cancer Center, University of California, Irvine-Medical Center, 101 The City Drive, Orange, CA 92868, USA
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  • Philip J. Disaia
    Affiliations
    The Division of Gynecologic Oncology, The Chao Family Comprehensive Cancer Center, University of California, Irvine-Medical Center, 101 The City Drive, Orange, CA 92868, USA
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  • John P. Fruehauf
    Correspondence
    Corresponding author. The Division of Hematology/Oncology, University of California, Irvine-Medical Center, CA 92868, USA. Fax: +1 714 456 7669.
    Affiliations
    The Section of Hematology & Oncology, The Chao Family Comprehensive Cancer Center, University of California, Irvine-Medical Center, 101 The City Drive, Orange, CA 92868, USA

    Oncotech, Inc., 15501 Red Hill Avenue, Tustin, CA 92780, USA
    Search for articles by this author
  • Author Footnotes
    1 Contributed equally to the preparation of this manuscript.

      Abstract

      Purpose.

      To compare the in vitro drug resistance profiles of advanced stage primary and recurrent epithelial ovarian cancer specimens using the tritiated thymidine uptake assay.

      Methods.

      Extreme drug resistance (EDR) to cisplatin, paclitaxel, 4-hydroxycyclophosphamide, and topotecan was determined for an unselected population of primary and metastatic malignant ovarian tissues, synchronous tumors (primary and metastatic tissues obtained from the same patient at diagnosis), and metachronous lesions (specimens from the same patient before and after chemotherapy).

      Results.

      For the large unselected population of malignant tissues (total, N = 6990; primary ovarian, N = 2031; metastatic ovarian, N = 4959), no statistically significant differences were discovered between primary tissues and metastatic lesions when a comparison was made between the percentage of tumors from each group that exhibited extreme drug resistance to the agents assayed. From the library of 6990 specimens, 119 synchronous pairings were identified. These synchronous lesions did not differ significantly in the %EDR between primary and metastatic sites in the same patient; approximately 10% shifted between low drug resistance and EDR. A total of 334 metachronous pairings were identified and the percentage of tissues that exhibited EDR also failed to show a significant difference when primary tumors were compared with matched recurrences in the same patient.

      Conclusions.

      For the agents studied, acquired resistance was not a function of disease site. In vitro drug resistance observed at recurrence was not influenced significantly by intervening therapy. It is possible that assay results at diagnosis could be used to guide subsequent therapy at relapse, especially when recurrent tissue is not available for analysis.

      Keywords

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