Secondary screening of platinum compounds in human ovarian cancer xenografts in nude mice

Boven, Epie; Nauta, M.M.; Schlüper, Hennie M.M.; Elferink, F.; Vijgh, W.J.F. van der; Pinedo, H.M.

doi:10.1016/0277-5379(85)90023-9

Cited by 23 publications

(8 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our laboratory we have found a good correlation between clinical data from phase II trials and the chemosensitivity of the panels of human soft tissue sarcoma xenografts and human ovarian cancer xenografts, both for conventional cytostatic agents and their analogues (Boven et al, 1985;Winograd et al, 1987;Boven, 1988;Boven et al, 1989;Boven et al, 1990;Boven, 1991). The validity of the xenograft model has not yet been proven for all classes of antitumour agents, such as antimetabolites.…”

Section: Discussionmentioning

confidence: 96%

The influence of the schedule and the dose of gemcitabine on the anti-tumour efficacy in experimental human cancer

Boven

Schipper²,

Erkelens³

et al. 1993

Br J Cancer

Self Cite

105

View full text Add to dashboard Cite

The therapeutic efficacy of gemcitabine, a new nucleoside analogue, was assessed in a variety of well-established human soft tissue sarcoma and ovarian cancer xenografts grown s.c. in nude mice. Tumour lines selected had different histological subtypes, growth rates and sensitivities to conventional cytostatic agents. The three different doses and schedules designed on the basis of a mean weight loss between 5% and 15% were i.p. injections of daily 3.5 mg kg-1 x 4, every 3 days 120 mg kg-1 x 4, and weekly 240 mg kg-1 x 2, which ultimately resulted in 19%, 10% and 4% toxic deaths, respectively. The weekly schedule induced > or = 50% growth inhibition in 2/4 soft tissue sarcoma and 4/6 ovarian cancer lines, while in three ovarian cancer lines > or = 75% growth inhibition was obtained. The anti-tumour effects of gemcitabine appeared to be similar or even better than previous data with conventional drugs tested in the same tumour lines. In comparison with the every 3 days schedule, the weekly and the daily schedule were less effective in 5/7 and 3/3 tumour lines (P < 0.001), respectively. In another experiment in three human tumour lines selected for their differential sensitivity to gemcitabine, weekly injections of 240 mg kg-1 x 6 did not result in a significant increase in the percentages of growth inhibition when compared to lower doses of 120 mg kg-1 or 60 mg kg-1 in the same schedule. However, the 240 mg kg-1 weekly x 6 schedule showed superior effects in 2/3 tumour lines in comparison with the same dose given every 2 weeks x 3 (P < 0.05). The preclinical activity of gemcitabine suggests that the drug can induce responses in soft tissue sarcoma and ovarian cancer patients. Our results further indicate that clinical trials of gemcitabine in solid tumour types should be designed on the basis of a schedule rather than a dose dependence.

show abstract

Section: Discussionmentioning

confidence: 96%

The influence of the schedule and the dose of gemcitabine on the anti-tumour efficacy in experimental human cancer

Boven

Schipper²,

Erkelens³

et al. 1993

Br J Cancer

Self Cite

105

View full text Add to dashboard Cite

show abstract

“…The actual doses for some drugs varied considerably from one study to another. Many chemotherapeutic studies use a treatment schedule in which a single MTD-dose is given [123], whereas others administer lower doses repeatedly [11,34].…”

Section: Drug Dosage and Toxicity In Hostmentioning

confidence: 99%

Human tumor xenografts as model for drug testing

et al. 1988

View full text Add to dashboard Cite

This paper reviews the history of xenografts, the endpoints commonly used to evaluate response and chemotherapeutic results obtained with serially maintained human tumor xenografts from different laboratories, and discusses the potential clinical relevance of the heterotransplant model for cancer chemotherapy. Specifically, an attempt is made to correlate the published xenograft data with the clinical data. Drug testing with different types of xenotransplanted tumors has shown that the response of xenografts obtained in immune-deficient animals is comparable to that in clinical practice. In addition, xenografts of a particular tumor type are able to identify agents of known clinical activity against that disease.

show abstract

“…Studies in mice have demonstrated that Pt concentrations in tumor tissue do not correlate with tumor regression activity [27]. It is interesting to note that drug-resistant cells from taxane-naïve patients were hypersensitive to taxanes [28].…”

mentioning

confidence: 99%

Reduced accumulation of platinum drugs is not observed in drug-resistant ovarian cancer cell lines derived from cisplatin-treated patients

Stukova

Hall

Tsotsoros

et al. 2015

Journal of Inorganic Biochemistry

View full text Add to dashboard Cite

The resistance of ovarian cancer towards front-line chemotherapy, usually cisplatin or carboplatin in combination with paclitaxel or docetaxel, remains a major clinical challenge. Resistance to these agents has been largely studied using cell lines selected for resistance to agents in vitro. We examined a series of paired cell lines derived from patients with ovarian cancer prior to chemotherapy (PEO1, PEO4, PEO14 and PEA1), and following the acquisition of resistance to a platinum-based chemotherapy regimen (PEO6, PEO23 and PEA2, respectively). All resistant patient lines showed resistance to cisplatin (2-5-fold), but this did not correspond with lowered accumulation. No general cross-resistance was observed for oxaliplatin, paclitaxel or docetaxel, and paclitaxel accumulation was not affected. PEO1 cells carrying BRCA2 mutations were hypersensitive to the PARP inhibitors olaparib and velaparib, but all other cell lines expressing functional forms of BRCA2 were less sensitive. While reduced drug accumulation was not observed, we believe these pairs of lines are of use to researchers studying Pt drug resistance and experimental therapeutics against drug-resistant ovarian cancer.

show abstract

Secondary screening of platinum compounds in human ovarian cancer xenografts in nude mice

Cited by 23 publications

References 10 publications

The influence of the schedule and the dose of gemcitabine on the anti-tumour efficacy in experimental human cancer

The influence of the schedule and the dose of gemcitabine on the anti-tumour efficacy in experimental human cancer

Human tumor xenografts as model for drug testing

Reduced accumulation of platinum drugs is not observed in drug-resistant ovarian cancer cell lines derived from cisplatin-treated patients

Contact Info

Product

Resources

About