Geertruida M. Kolfschoten

Leiden University Medical Center

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Herbert M. Pinedo

Amsterdam University Medical Centers

Epie Boven

Vrije Universiteit Amsterdam

Jan Paul Medema

University of Amsterdam

Bérengère Pradet‐Balade

Université de Montpellier

Michael Hahne

Institut de Génétique Moléculaire de Montpellier

T.M. Hulscher

Vrije Universiteit Amsterdam

Caroline A.M. Erkelens

Amsterdam UMC Location VUmc

José A. García‐Sanz

Centro de Investigaciones Biológicas Margarita Salas

Willy J.M. Jansen

Vrije Universiteit Amsterdam

J van Ark-Otte

Vrije Universiteit Amsterdam

Cooperative Institutions

Vrije Universiteit Amsterdam

University of Amsterdam

Amsterdam UMC Location VUmc

Amsterdam University Medical Centers

Centre National de la Recherche Scientifique

Consejo Superior de Investigaciones Científicas

Centro Nacional de Biotecnología

Universidad Autónoma de Madrid

University Medical Center Utrecht

Leiden University

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Variation in the kinetics of caspase-3 activation, Bcl-2 phosphorylation and apoptotic morphology in unselected human ovarian cancer cell lines as a response to docetaxel

Biochemical Pharmacology (2002)

Geertruida M. Kolfschoten Theresia M. Hulscher Monique C.A. Duyndam Herbert M. Pinedo Epie Boven

10.1016/s0006-2952(01)00895-4

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Citations (58)

TWE-PRIL; a fusion protein of TWEAK and APRIL

Biochemical Pharmacology (2003)

Geertruida M. Kolfschoten Bérengère Pradet‐Balade Michael Hahne Jan Paul Medema

Furin

Cell surface receptor

10.1016/s0006-2952(03)00493-3

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Citations (35)

Drug resistance features and S-phase fraction as possible determinants for drug response in a panel of human ovarian cancer xenografts

British Journal of Cancer (2000)

Geertruida M. Kolfschoten T.M. Hulscher Herbert M. Pinedo Epie Boven

Multidrug resistance (MDR) and more specifically the expression of P-glycoprotein (Pgp) have been studied extensively in vitro. Unfortunately, it appears that the predictive value of MDR recognized in vitro is mostly an incorrect measure to determine the responsiveness of a particular tumour in the clinic. This misunderstood or overvalued role of MDR might explain the failure of strategies to reverse Pgp function by the use of modulators in solid tumours. To obtain more insight in in vivo drug resistance we investigated a panel of 15 human ovarian cancer xenografts consisting of the most common histological subtypes known in ovarian cancer patients. The response rate to cisplatin, cyclophosphamide and doxorubicin in the xenografts resembled the results of phase II trials with these agents in ovarian cancer patients. This resemblance justifies drug resistance studies in this experimental in vivo human tumour system. We determined the expression levels of MDR 1, MRP 1, LRP and topoisomerase IIalpha mRNA by the RNase protection assay and the presence of MRP1 and LRP proteins by immunohistochemistry. The S-phase fraction was investigated as a separate parameter by flow cytometry. In none of the 15 ovarian cancer xenografts was MDR 1 expression detectable. The expression levels of MRP 1 and LRP were low to moderate and resembled the presence of the MRP1 and LRP proteins. There was a weak, inverse relationship between the expression levels of LRP and sensitivity to cisplatin and cyclophosphamide (r = -0.44 and -0.45), but not to doxorubicin. The levels of topoisomerase IIalpha varied among the xenografts (0.73-2.66) and failed to correlate with doxorubicin resistance (r = 0.14). The S-phase fraction, however, showed a relation with the sensitivity to cisplatin (r = 0.66). Among the determinants studied in ovarian cancer in vivo, LRP mRNA and the S-phase fraction were the best predictive factors for drug response and most specifically for the activity of cisplatin.

10.1054/bjoc.2000.1373

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Citations (28)

Time-Dependent Changes in Factors Involved in the Apoptotic Process in Human Ovarian Cancer Cells as a Response to Cisplatin

Gynecologic Oncology (2002)

Geertruida M. Kolfschoten T.M. Hulscher S. Mariette Schrier Viola M. M. van Houten Herbert M. Pinedo

Fragmentation

10.1006/gyno.2001.6537

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Anti-tumor activity of CPT-11 in experimental human ovarian cancer and human soft-tissue sarcoma

International Journal of Cancer (1997)

Willy J.M. Jansen Geertruida M. Kolfschoten Caroline A.M. Erkelens J van Ark-Otte Herbert M. Pinedo

CPT-11, a semi-synthetic derivative of camptothecin, was investigated for its activity in panels of 15 human ovarian-cancer lines and 10 human soft-tissue sarcoma lines grown s.c. in nude mice. Various factors were analyzed that may be of influence on the extent of tumor-growth inhibition induced by CPT-11. At equitoxic doses, CPT-11 was more effective in the daily ×5 schedule than the weekly ×2 schedule, although a 2-fold higher dose was administered in the weekly ×2 schedule. Since i.p. and i.v. injections were similarly effective, the selected treatment schedule was 20 mg/kg i.p. daily ×5, starting when tumors measured approximately 150 mm3. Growth inhibition of ≥75% was obtained in 8/15 human ovarian-cancer lines and in 6/10 human soft-tissue sarcoma lines. A weak correlation was found between topoisomerase-I mRNA in xenograft tissues and sensitivity to CPT-11. Relative topoisomerase-I expression was highest in MRI-H-207 and WLS-160 xenografts, in which CPT-11 was able to induce cures of all tumors. The high efficacy in the 2 panels of human tumor lines suggests over-prediction of its potential clinical activity in these tumor types. The difference in efficacy of CPT-11 between species may be related to the metabolism of the drug, since CPT-11 is converted more efficiently into SN-38 in mice. In addition, mice may be less sensitive to SN-38-induced side-effects. On the basis of the preclinical data, frequent administration of lower doses of CPT-11 should be considered in order to increase response rates in the clinic. Int. J. Cancer 73:891–896, 1997. © 1997 Wiley-Liss, Inc.

Camptothecin

Growth inhibition

10.1002/(sici)1097-0215(19971210)73:6<891::aid-ijc22>3.0.co;2-6

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Citations (37)

Development of a Panel of 15 Human Ovarian Cancer Xenografts for Drug Screening and Determination of the Role of the Glutathione Detoxification System

Gynecologic Oncology (2000)

Geertruida M. Kolfschoten Herbert M. Pinedo P Scheffer Hennie M.M. Schlüper Caroline A.M. Erkelens

Growth inhibition

10.1006/gyno.1999.5689

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Citations (37)