Highly Specific Prediction of Antineoplastic Drug Resistance With an In Vitro Assay Using Suprapharmacologic Drug Exposures

Kern, David H.; Weisenthal, Larry M.

doi:10.1093/jnci/82.7.582

Cited by 164 publications

(117 citation statements)

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“…The responding patient population, on the other hand, is drug sensitive and the probability for true drug interactions is consequently expected to be higher. However, one should also note that the frequency of additive interactions in the present study may (Valeriote & Lin, 1975 (Berenbaum, 1989 predicted the in vitro activity of the combination, based on a 40% SI cut-off limit for discriminating sensitive from resistant (Larsson et al, 1992b (Weisenthal & Kern, 1990;Bosanquet, 1991). See Materials and methods.…”

Section: Discussionmentioning

confidence: 77%

“…Correlations were performed at a previously specified concentration producing a significant scatter of SI values (Larsson et al, 1992a) using either a fixed cut-off line (SI = 40%) determined from comparison with previous results using the differential staining cytotoxicity assay (Larsson et al, 1992b) or the use of drug specific relative cut-off lines (median and median + 1 standard deviation (s.d. ; Kern & Weisenthal, 1990;Bosanquet, 1991 (Kern & Weisenthal, 1990;Bosanquet, 1991).…”

Section: In Vitro-in Vivo Comparisonmentioning

confidence: 99%

“…Short-term in vitro drug sensitivity assays have raised the possibility of predicting clinical outcome and selecting optimal components for chemotherapeutic protocols for individual patients (Bosanquet, 1991;Kern & Weisenthal, 1990;Hongo et al, 1990;Larsson et al, 1992a;Pieters et al, 1991;Von Hoff, 1988;Weisenthal & Lippman, 1985). Although the majority of patients are treated with drug combinations, these assays most commonly test single agents.…”

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confidence: 99%

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In vitro testing of chemotherapeutic drug combinations in acute myelocytic leukaemia using the fluorometric microculture cytotoxicity assay (FMCA)

Larsson

Fridborg²,

Kristensen³

et al. 1993

Br J Cancer

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Section: Discussionmentioning

confidence: 77%

Section: In Vitro-in Vivo Comparisonmentioning

confidence: 99%

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confidence: 99%

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In vitro testing of chemotherapeutic drug combinations in acute myelocytic leukaemia using the fluorometric microculture cytotoxicity assay (FMCA)

Larsson

Fridborg²,

Kristensen³

et al. 1993

Br J Cancer

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“…Currently available assays for use in oncology have relatively low positive predictive values (70%), but excellent negative predictive values (>90%) [6 -8]. Thus, while in vitro drug response assays have not been as reliable at predicting drug sensitivity in the clinic, they may become useful in identifying those agents that have less than a 3% chance of clinical benefit [9]. Recently published data sets from non-randomized studies suggest that patients who receive agents to which their tumor is resistant to in vitro progress more rapidly and have shorter survival times [7,8,10 -12].…”

Section: Introductionmentioning

confidence: 99%

Conservation of in vitro drug resistance patterns in epithelial ovarian carcinoma

Tewari

Mehta

Burger

et al. 2005

Gynecologic Oncology

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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. D

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“…Unfortunately, although the accuracy of in vitro systems in predicting drug resistance is very high, the accuracy in predicting sensitivity is very low [7] . The application of in vitro results to individual patients has therefore been limited to avoid the administration of drugs that are ineffective in vitro.…”

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confidence: 99%

Comparison of clinical staging of benign and malignant ovarian tissues with DNA flow cytometry

Thornthwaite

Stanfill²,

Ahmed³

2013

JST

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The prevention, diagnosis and treatment of ovarian cancer are major issues. The outcome of patients with advanced ovarian cancer is poor despite aggressive therapy including surgery, combination drug chemotherapy and radiation treatments. From the literature, the direct correlation between DNA ploidy and survival is greatly enhanced using high resolution DNA measurements, which results in a coefficient of variation (CV) range between 1%-2% (1.42 ± 0.19, n=66) for trout red blood cells (TRBC) and 2%-3% (2.18 ± 0.46 SD, n=22) for tonsil nuclei derived from formalin-fixed, paraffin-embedded tissues (deparaffinated). DNA nuclear determinations from 50 ovarian cancer and 21 benign patients is presented. This was accomplished by measuring the DNA content of nuclei simultaneously isolated from deparaffinated tissues, stained with the fluorescent DNA specific dye, 4', 6-diamidino-1-phenylindole (DAPI) and analyzed on a high resolution flow cytometer. A high percentage of aneuploidy (92.0%) was determined from the ovarian cancer patients, especially of the aneuploid DNA histogram types, such as hypodiploid, multiploid and hypertetraploid (64.0%), which have shown poor prognosis in a variety of cancers including ovarian. Furthermore, aneuploidy was detected in 23.8% of the benign patients. DNA flow cytometry may complement pathological assessment of ovarian cancer to better determine malignancy, thus justifying a closer follow-up with more specialized approaches to treatment in clinical trials that involve new therapies including the use of chemically defined, natural products, which may help offset the overall poor prognosis seen in ovarian cancer.

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Highly Specific Prediction of Antineoplastic Drug Resistance With an In Vitro Assay Using Suprapharmacologic Drug Exposures

Cited by 164 publications

References 0 publications

In vitro testing of chemotherapeutic drug combinations in acute myelocytic leukaemia using the fluorometric microculture cytotoxicity assay (FMCA)

In vitro testing of chemotherapeutic drug combinations in acute myelocytic leukaemia using the fluorometric microculture cytotoxicity assay (FMCA)

Conservation of in vitro drug resistance patterns in epithelial ovarian carcinoma

Comparison of clinical staging of benign and malignant ovarian tissues with DNA flow cytometry

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