Unlabelled: Background chemotherapy is part of most breast cancer (BC) treatment schedules. However, a substantial fraction of BC tumors does not respond to the treatment. Unfortunately, no standard biomarkers exist for response prediction. Therefore, we aim to develop ex vivo sensitivity assays for two types of commonly used cytostatics (i.e., platinum derivates and taxanes) on organotypic BC tissue slices.
Methods: Ex vivo cisplatin sensitivity assays were established using organotypic tissue slices derived from the surgical resection material of 13 primary BCs and 20 fresh histological biopsies obtained from various metastatic sites. Furthermore, tissue slices of 10 primary BCs were used to establish a docetaxel ex vivo sensitivity assay.
Results: Cisplatin sensitivity was assessed by tissue morphology, proliferation and apoptosis, while the relative increase in the mitotic index was discriminative for docetaxel sensitivity. Based on these read-outs, a scoring system was proposed to discriminate sensitive from resistant tumors for each cytostatic. We successful completed the cisplatin sensitivity assay on 12/16 (75%) biopsies as well.
Conclusions: We developed an ex vivo cisplatin and docetaxel assay on BC slices. We also adapted the assay for biopsy-sized specimens as the next step towards the correlation of ex vivo test results and in vivo responses.
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http://dx.doi.org/10.3390/cancers14051252 | DOI Listing |
Cancer Drug Resist
December 2024
Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava 84505, Slovak Republic.
Mutations in the mitochondrial (mt) genome contribute to metabolic dysfunction and their accumulation relates to disease progression and resistance development in cancer cells. This study explores the mutational status of the mt genome of cisplatin-resistant -sensitive testicular germ cell tumor (TGCT) cells and explores its association with their respiration parameters, expression of respiratory genes, and preferences for metabolic pathways to reveal new markers of therapy resistance in TGCTs. Using Illumina sequencing with Twist Enrichment Panel, the mutations of mt genomes of sensitive 2102EP, H12.
View Article and Find Full Text PDFBJU Int
January 2025
Department of Urology, University of Duisburg-Essen, Essen, Germany.
Objective: To investigate the expression patterns of Nectin-4, the target molecule of the antibody-drug conjugate enfortumab vedotin (EV), in relation to histological and molecular subtypes of urothelial bladder cancer (UBC).
Patients And Methods: We assessed the protein expression patterns of Nectin-4 in a spatially organised tissue microarray containing 1386 tissue cores from 314 consecutive patients with UBC who underwent radical cystectomy (2005-2018). Results were correlated with clinicopathological and follow-up data, as well as with different spatial locations (tumour central vs tumour-normal interface and primary tumour vs lymph node [LN] metastases).
Anal Chim Acta
February 2025
Department of Chemical Biology, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383, Wrocław, Poland. Electronic address:
Background: Mammalian metallothioneins (MTs) play a crucial role in maintaining Zn(II) and Cu(I) homeostasis, as well as regulating the cellular redox potential. They are involved in cancer resistance to cisplatin-related drugs and the sequestration of toxic metal ions. To investigate their participation in specific physiological and pathological processes, it is imperative to develop an analytical method for measuring changes in protein concentration both in vitro and in vivo.
View Article and Find Full Text PDFNucleosides Nucleotides Nucleic Acids
January 2025
Division of Hematology, Department of Internal Medicine, Medical Faculty, Tekirdağ Namık Kemal University, Tekirdağ, Turkey.
Breast cancer is the most common malignancy that affects women. MicroRNAs (miRNAs) play an essential role in cancer therapy and regulate many biological processes such as cisplatin resistance. The study's objective was to determine whether miR-182 dysregulation was the cause of cisplatin resistance in TNBC cell line MDA-MB-231.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
Background/objectives: Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with a rising global incidence and poor prognosis, largely due to late-stage diagnosis and limited effective treatment options. Standard chemotherapy regimens, including cisplatin and gemcitabine, often fail because of the development of multidrug resistance (MDR), leaving patients with few alternative therapies. Doxycycline, a tetracycline antibiotic, has demonstrated antitumor effects across various cancers, influencing cancer cell viability, apoptosis, and stemness.
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