Ovarian carcinoma cells in culture: Assessment of drug sensitivity by clonogenic assay

Simmonds, A P; McDonald, Evangeline

doi:10.1038/bjc.1984.178

Cited by 21 publications

(10 citation statements)

References 10 publications

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“…In the monolayer assay described here 39% of all tumours tested were very sensitive to CIS (<40% of control) and 71% showed some sensitivity (<60% of control). These values are very similar to those reported by Simmonds and McDonald (1984) for CIS sensitivity (48% sensitive, 79% intermediate + sensitive). Thus, in spite of their intrinsic differences the monolayer and clonogenic assays are predicting similar response rates of primary ovarian carcinoma cells to CIS.…”

Section: Discussionsupporting

confidence: 80%

“…that it can be used to show variations in the chemosensitivities of human ovarian tumours which reflect the clinically found pattern of response to chemotherapy. The overall success rate with the assay was -40% which is considerably lower than the 80% success rate which has been reported by groups using the clonogenic assay (Von Hoff et al, 1983;Simmonds & McDonald, 1984). However, the number of drug tests achieved for each successful monolayer culture exceeds that which is normally possible for the clonogenic assay.…”

Section: Discussionmentioning

confidence: 52%

“…The microtitration assay was chosen for this study in preference to the clonogenic assay used by other groups, (e.g. Hamburger et al, 1978;Courtenay & Mills, 1978;Von Hoff et al, 1983;Simmonds & McDonald, 1984) because of the low cell requirement which offers the facility of multiple drug screening over several drug concentrations.…”

mentioning

confidence: 99%

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Cis-platinum and ovarian carcinoma. In vitro chemosensitivity of cultured tumour cells from patients receiving high dose cis-platinum as first line treatment

Wilson

Ford²,

Newman³

et al. 1987

Br J Cancer

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Correlation of in vitro sensitivity to cis-platinum with clinical response to cis-platinum assessed using CT scan and second-look laparotomy, showed positive correlation in 9/11 (89%) patients (8 = S/S; 1 = R/R); positive correlation between in vitro sensitivity to phosphoramide mustard and clinical response was also found in 4/6 patients receiving cyclophosphamide (3 = S/S; 1= R/R). All patients with sensitive tumours showed a clinical response to cis-platinum.Comparison of cis-platinum sensitivity with sensitivity to phosphoramide mustard and melphalan showed that some tumours were sensitive only to cis-platinum; resistance to cis-platinum and sensitivity to phosphoramide mustard/melphalan was an infrequent occurrence. Some tumours which were resistant to cisplatinum showed sensitivity to adriamycin and bleomycin, particularly those from untreated patients. Sensitivity to 5-fluorouracil and resistance to cis-platinum was found in approximately equal proportions of tumours in both the treated and untreated groups.Although response rates of approximately 50% have been achieved with alkylating agents in the treatment of ovarian cancer, survival times have not been significantly prolonged in this disease which still represents the leading cause of death from gynaecological cancer in the UK. New chemotherapeutic regimes are under continual evaluation and the finding that cis-platinum II diammine dichloride (CIS) could produce response rates of 30-40% in heavily pre-treated patients (Wiltshaw & Kroner, 1976;Bruckner et al., 1978) argued for its trial as a first-line drug in the treatment of ovarian cancer. At the time this study was started there were no previous reports which described the use of high dose CIS (1OOmgm-2) in untreated patients with ovarian carcinoma, and a clinical trial was initiated to evaluate this regime. In conjunction with this, a laboratory study was set up to evaluate the in vitro response of tumour cells from trial patients to CIS. The patient group was potentially well suited to such a study because (a) most patients received a single drug, (b) there was surgical evidence of tumour burden at the onset of chemotherapy and (c) stringent response criteria including the use of computerised tomography and second look laparotomies (2LL) were used to evaluate response.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 52%

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Cis-platinum and ovarian carcinoma. In vitro chemosensitivity of cultured tumour cells from patients receiving high dose cis-platinum as first line treatment

Wilson

Ford²,

Newman³

et al. 1987

Br J Cancer

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“…Several investigators have reported that patients pretreated with DDP had low-level resistance to DDP, and that human ovarian carcinoma cell lines derived from the patients' tumor at the time the tumor became unresponsive to DDP were only two-to fourfold resistant to DDP (3)(4)(5)(6). In several in vivo murine models, DDP-resistant cell lines could be isolated from tumors treated with as few as two doses of DDP (53,54).…”

Section: Methodsmentioning

confidence: 99%

“…Cells selected for resistance to many antimetabolites (1), and to drugs participating in the multiple drug resistance phenotype (2), often exhibit very high levels of resistance. In contrast, both in vitro and in vivo selection with DDP at clinically relevant intensities usually results in low-level resistant cells which are only two-to fourfold resistant to this drug (3)(4)(5)(6). Attempts to enhance the sensitivity to DDP have focused on strategies such as reduction of glutathione (7)(8)(9)(10) and inhibition of DNA repair ( 1,12).…”

Section: Introductionmentioning

confidence: 99%

Epidermal growth factor regulates the in vitro sensitivity of human ovarian carcinoma cells to cisplatin.

Christen

Hom²,

Porter³

et al. 1990

J. Clin. Invest.

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Chemosensitivity testing in ovarian cancer

Sevin¹,

Perras²,

Averette³

et al. 1993

Cancer

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Most patients with ovarian cancer currently are treated primarily with surgery and chemotherapy. Drug selection usually is not based on individualized in vitro sensitivity studies but on reported response rates of clinical trials. Attempts to include in vitro chemosensitivity testing into the management of ovarian cancer have been disappointing to clinicians. Tumor cells from fresh human ovarian cancer do not grow well under artificial in vitro growth conditions. The selection of cells that happen to proliferate in vitro (e.g., human tumor clonogenic assay) has resulted in low plating efficiencies (0.001-0.1% of plated cells). The vigorous mechanical and enzymatic tumor disaggregation, done to obtain a single-cell suspension, further reduces the number of cells that grow in vitro, resulting in low overall evaluability rates of 40-70% for the human tumor clonogenic assay. At the University of Miami, a new in vitro chemosensitivity assay was developed that detected the decrease in total tumor cell viability by measuring intracellular adenosine triphosphate as a function of in vitro drug response. Preliminary data on 31 tumor tissues from patients, which was evaluated with this method, showed a sensitivity of 92% and a specificity of 100%. Since these initial studies, data were gathered on more than 150 fresh gynecologic tumor specimens to evaluate single drugs and drug combinations at five concentrations (range, 10-500% of reported peak plasma concentrations). The evaluability rate for ovarian tumors was more than 90%. Some tumors showed almost complete cell kill at the lowest drug concentration; others had only a limited response at the highest level. Drug-response patterns also were variable for combined drug exposure. These findings underscore the heterogeneity of drug response in morphologically similar tumors and the importance of characterizing indi-

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Ovarian carcinoma cells in culture: Assessment of drug sensitivity by clonogenic assay

Cited by 21 publications

References 10 publications

Cis-platinum and ovarian carcinoma. In vitro chemosensitivity of cultured tumour cells from patients receiving high dose cis-platinum as first line treatment

Cis-platinum and ovarian carcinoma. In vitro chemosensitivity of cultured tumour cells from patients receiving high dose cis-platinum as first line treatment

Epidermal growth factor regulates the in vitro sensitivity of human ovarian carcinoma cells to cisplatin.

Chemosensitivity testing in ovarian cancer

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