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Ex vivo assays to predict enhanced chemosensitization by hyperthermia in urothelial cancer of the bladder
- Source :
- PLoS ONE, 13(12):0209101. PUBLIC LIBRARY SCIENCE, PLoS One (online), 13(12):e0209101. Public Library of Science, PLoS ONE, PLoS ONE, Vol 13, Iss 12, p e0209101 (2018)
- Publication Year :
- 2018
-
Abstract
- IntroductionBladder cancer (urothelial carcinoma) is a common malignancy characterized by high recurrence rates and intense clinical follow-up, indicating the necessity for more effective therapies. Current treatment regimens include intra-vesical administration of mitomycin C (MMC) for non-muscle invasive disease and systemic cisplatin for muscle-invasive or metastatic disease. Hyperthermia, heating a tumor to 40-44 degrees C, enhances the efficacy of these chemotherapeutics by various modes of action, one of which is inhibition of DNA repair via homologous recombination. Here, we explore whether ex vivo assays on freshly obtained bladder tumors can be applied to predict the response towards hyperthermia.Material and methodsThe cytochrome C release assay (apoptosis) and the RAD51 focus formation assay (DNA repair) were first established in the bladder cancer cell lines RT112 and T24 as measurements for hyperthermia efficiency, and subsequently tested in freshly obtained bladder tumors (n = 59).ResultsHyperthermia significantly increased the fraction of apoptotic cells after cisplatin or MMC treatment in both RT112 and T24 cells and in most of the bladder tumors (8/10). The RAD51 focus formation assay detected both morphological and numerical changes of RAD51 foci upon hyperthermia in the RT112 and T24 cell lines. In 64% of 37 analyzed primary bladder tumor samples, hyperthermia induced similar morphological changes in RAD51 foci.ConclusionThe cytochrome C assay and the RAD51 focus formation assay are both feasible on freshly obtained bladder tumors, and could serve to predict the efficacy of hyperthermia together with cytotoxic agents, such as MMC or cisplatin.
- Subjects :
- 0301 basic medicine
Epidemiology
medicine.medical_treatment
Cancer Treatment
Apoptosis
Pathology and Laboratory Medicine
urologic and male genital diseases
Biochemistry
THERAPY
HOMOLOGOUS RECOMBINATION
0302 clinical medicine
Medicine and Health Sciences
Medicine
Multidisciplinary
Cell Death
Cancer Risk Factors
Cytochromes c
CHEMOTHERAPY
Bladder Cancer
3. Good health
Nucleic acids
Oncology
Cell Processes
CROSS-LINKS
030220 oncology & carcinogenesis
Anatomy
Research Article
medicine.drug
Hyperthermia
CARCINOMA
Science
Mitomycin
Bladder
Urology
Genetic Causes of Cancer
MITOMYCIN-C
Focus-Forming Assay
DNA repair
CELL-LINES
Research and Analysis Methods
03 medical and health sciences
CISPLATIN
Signs and Symptoms
SDG 3 - Good Health and Well-being
FUTURE
Diagnostic Medicine
Cell Line, Tumor
Genetics
Carcinoma
Humans
Molecular Biology Techniques
Molecular Biology
Cisplatin
REPAIR
Molecular Biology Assays and Analysis Techniques
Chemotherapy
Bladder cancer
business.industry
Mitomycin C
Biology and Life Sciences
Cancers and Neoplasms
Hyperthermia, Induced
Renal System
Cell Biology
DNA
medicine.disease
Genitourinary Tract Tumors
030104 developmental biology
Urinary Bladder Neoplasms
Medical Risk Factors
Cancer research
business
Ex vivo
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, 13(12):0209101. PUBLIC LIBRARY SCIENCE, PLoS One (online), 13(12):e0209101. Public Library of Science, PLoS ONE, PLoS ONE, Vol 13, Iss 12, p e0209101 (2018)
- Accession number :
- edsair.doi.dedup.....eb99773740e1c78a39a626dd3b763a7a