Carlier, Charlotte

Ceelen, Wim

Thomale, Jürgen

Ghent University Academic Bibliography

Cytoreductive surgery (CRS) followed by intraperitoneal chemoperfusion (IPEC) with platinum (Pt) – based drugs benefits selected patients withperitoneal carcinomatosis (PC). Nevertheless, despite the initially successful response to the chemotherapy, 80% of women will eventually developrecurrent peritoneal disease, which can only arise from minimal residual disease left after primary CRS, and resistant tumor cells. However, little isknown about the amount and distribution of cisplatin-DNA adducts and the influence of combined hyperthermia. Therefore, we want to analyzethe relative contribution of structurally defined cisplatin-DNA adducts.ExperimentTumor tissue samples were obtained from patients with PC from primary or recurrent serous epithelial ovarian cancer (OC), who underwent CRSimmediately followed by 90 min. of chemoperfusion. Concerning the chemoperfusion, patients were randomized into 4 different groups: IPEC(37-38°C) or hyperthermic IPEC (40-41°C; HIPEC) treatment with a cisplatin dose of 120 or 75 mg/m². Tumor nodules were removed from eachpatient after (H)IPEC and snap-frozen in liquid nitrogen. Tumor tissue sections of 5 µm were cut and stained with the monoclonal antibody R-C18to investigate the amount and distribution of 1, 2 Pt– guanine, guanine adducts (1, 2 Pt-[GpG]) in the nuclear DNA of individual cells.Additionally, Haematoxylin and Eosin (H&E) and Paired Box gene 8 (PAX-8) stainings confirmed the presence of epithelial ovarian cancer cells inthe tissues.Results2Before (H)IPEC31After (H)IPECCryo-sections of tumor tissues excised before andafter (H)IPEC were stained with the ICA protocol.DAPI staining showed DNA content (1); IF stainingwith Mab R-C18 showed 1, 2 Pt-[GpG] DNAadducts (2); Overlay of 1 and 2 (3). Magnification40XConsecutive cryo-sections of tumor tissuesexcised after (H)IPEC were stained with H&E andPAX-8. Overview of the tumor tissues (A); Regionof interest, which corresponds to image 3 of theICA assay (B). Magnification: A = 40X; B = 200XP409H&E PAX-8A B ABConclusionsICA staining:- is a highly sensitive and specific staining method- made it possible to visualize and quantify the 1, 2 Pt-[GG] adducts in human tumor tissues after (H)IPEC- can be correlated to other histological images, which may be of particular interest when investigating the influence of e.g. transportmechanisms in the acquisition of Pt resistance.2Analysis of specific platinum - DNA adducts after clinical intraoperative intraperitoneal chemoperfusion of ovarian cancer patientsCharlotte Carlier1, Jürgen Thomale² and Wim Ceelen11Department of Surgery, Ghent University, Ghent, Belgium² Department of DNA repair, Essen University hospital, Essen 45122, GermanyCorresponding Author: charlotte.carlier@ugent.beBackground and purposeP

Analysis of specific platinum-DNA adducts after clinical intraoperative intraperitoneal chemoperfusion of ovarian cancer patients

https://biblio.ugent.be/publication/8501536/file/8501542

Analysis of specific platinum-DNA adducts after clinical intraoperative intraperitoneal chemoperfusion of ovarian cancer patients

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Ghent University Academic Bibliography