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Abstract: Background. Electrochemotherapy is a tumour ablation modality, based on electroporation of the cell membrane, allowing non-permeant anticancer drugs to enter the cell, thus augmenting their cytotoxicity by orders of magnitude. In preclinical studies, bleomycin and cisplatin proved to be the most suitable for clinical use. Intravenous administration of cisplatin for electrochemotherapy is still not widely accepted in the clinics, presumably due to its lower antitumor effectiveness, but adjuvant therapy by immunomodulatory or vascular-targeting agents could provide a way for its potentiation. Hence, the aim of the present study was to explore the possibility of adjuvant tumour necrosis factor % (TNF-%) therapy to potentiate antitumor effectiveness of electrochemotherapy with intravenous cisplatin administration in murine sarcoma. Materials and methods. In vivo study was designed to evaluate the effect of TNF-% applied before or after the electrochemotherapy and to evaluate the effect of adjuvant TNF-% on electrochemotherapy with different cisplatin doses. Results. A synergistic interaction between TNF-% and electrochemotherapy was observed. Administration of TNF-% before the electrochemotherapy resulted in longer tumour growth delay and increased tumour curability, and was significantly more effective than TNF-% administration after the electrochemotherapy. Tumour analysis revealed increased platinum content in tumours, TNF-% induced blood vessel damage and increased tumour necrosis after combination of TNF-% and electrochemotherapy, indicating an anti-vascular action of TNF-%. In addition, immunomodulatory effect might have contributed to curability rate of the tumours. Conclusion. Adjuvant intratumoural TNF-% therapy synergistically contributes to electrochemotherapy with intravenous cisplatin administration. Due to its potentiation at all doses of cisplatin, the combined treatment is predicted to be effective also in tumours, where the drug concentration is suboptimal or in bigger tumours, where electrochemotherapy with intravenous cisplatin is not expected to be sufficiently effective.
Keywords: electrochemotherapy, TNF, adjuvant immunotherapy, cisplatin
Published in DiRROS: 17.04.2024; Views: 99; Downloads: 20
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Keywords: hypoxia, pimonidazole, Glut-1, electrochemotherapy
Published in DiRROS: 08.03.2024; Views: 99; Downloads: 31
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Abstract: Apoptosis is a distinct form of cell death characterised by specific morphological features and regulated by complex molecular mechanisms. Its deregulation is fundamental for tumour growth and progression and, moreover, anticancer therapies suppress tumour growth mainly by induction of apoptosis. Since the extent of apoptosis in a tumour may have prognostic as well as therapeutic implications, much effort has been invested in developing specificmethods that can be routinely used to detect apoptotic cells in archival formalin fixed paraffin-embedded tissue. Complex molecular pathways are involved in the regulation of apoptosis. Pro-apoptotic signals trigger activation of caspases that specifically cleave target proteins. Cleavage of proteins (caspase substrates) is responsible for morphological changes of apoptotic cells and DNA fragmentation. In the last decade, detection of apoptotic cells in formalin fixed tumour tissue sections has been based mainlyon morphology and characteristic DNA fragmentation. Recently, specific antibodies to activated caspases and cleaved target proteins (including cytokeratin 18, actin and PARP) have been produced that enable accurate detection of apoptosis in paraffin sections.
Published in DiRROS: 06.02.2024; Views: 142; Downloads: 35
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Keywords: Ti6Al7Nb implant alloy cementless hip endoprostheses, roughness, Al2O3 grit blasting, surface and subsurface implant contamination, cytotoxicity, aseptic loosening, infection, osseointegration
Published in DiRROS: 01.02.2024; Views: 172; Downloads: 71
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Abstract: The aimof this study was to test the hypothesis on the protective role of thyroxin administration before and during irradiation on the occurrence of thyroid carcinoma in rats. Application of thyroxin before and during irradiation was expected to decrease production of thyrotropin by the hypophyseal feedback mechanism, caused by radiation damage of thyroid tissue. Stabilizing the thyroid cells in this way during irradiation would thus make them less radiosensitive. In the experiment, we first divided 81 three to fourweek old Wistar strain rats of both sexes into two groups, i.e. thyroxin (T4) and water (H2O). The T4 rats were injected 1% thyroxin solution (0.01 mg/100 g body weight) twice a day for 15 days, while the H2O rats received saline in the same way. After ten days, the two main groups were divided each into two subgroups. The rats from both irradiated subgroups (T4/X and (H2O/X) recieved 10 Gy to the neck area. They were iradiated with a telecobalt machinefor five consecutive days with one direct field. During a two years follow - up, all moribund animals were sacrificed and their thyroid glands taken. The rest of the thyroid glands were taken at the end of the experiment.All glands were pathohistologically analysed. Besides, all suspicious and enlarged extrathyroid organs and tissues were examined and the occurrence of tumors was noted. Pathohistological examination revealed the occurrence of 8 thyroid carcinomas and 7 adenomas in the H2O/X group, and 3 adenomas in the T4/X group. In the iradiated group of rats without thyroxin, significantly (P = 0.01) more thyroid carcinomas occurred than in the irradiated group without thyroxin.
Published in DiRROS: 19.01.2024; Views: 195; Downloads: 45
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