11. Long term response of electrochemotherapy with reduced dose of bleomycin in elderly patients with head and neck non-melanoma skin cancerČrt Jamšek, Gregor Serša, Maša Omerzel, Aleš Grošelj, 2020, original scientific article Abstract: . Electrochemotherapy (ECT) is a local cancer treatment based on electroporation where the electric field is used to enhance cell membrane permeability and thereby facilitating the transition of chemotherapeutic agents into the cell. For the treatment of non-melanoma skin cancer, a standard dosage of 15,000 IU/m2 bleomycin (BLM) is used. The aim of the present study was to evaluate the long-term ECT response in the group of elderly patients with non-melanoma skin cancer treated with a reduced dose of BLM in comparison to the outcome in the patients treated with the standard dose of BLM. Patients and methods. Twenty-eight patients older than 65 years, with a total of 52 non-melanoma skin lesions were included in the study. Twelve patients (24 lesions) in the experimental group received a reduced dose of BLM (10,000 IU/m2), 16 patients (28 lesions) were treated with a standard dose of BLM (15,000 IU/m2). Results. No statistically significant difference in tumor control was observed between both groups. In the experimental group, tumors recurred in 39.0% of treated lesions in a median follow-up time of 28 months. In the control group, the recurrence rate of treated lesions was 15.4% in a median follow-up time of 40 months. Conclusions. ECT with a reduced dose of BLM is a feasible treatment option for elderly patients with equal efficacy to standard dose treatment and should be considered as a treatment modality in advanced aged patients with comorbidities, where overall life expectancy is poor
Keywords: electrochemotherapy, bleomycin, non-melanoma skin cancer
Published in DiRROS: 12.07.2024; Views: 149; Downloads: 43
 Full text (269,64 KB) |
12. Pulsed low dose-rate irradiation response in isogenic HNSCC cell lines with different radiosensitivityVesna Todorović, Ajda Prevc, Martina Nikšić Žakelj, Monika Savarin, Simon Buček, Blaž Grošelj, Primož Strojan, Maja Čemažar, Gregor Serša, 2020, original scientific article Abstract: . Management of locoregionally recurrent head and neck squamous cell carcinomas (HNSCC) is challenging due to potential radioresistance. Pulsed low-dose rate (PLDR) irradiation exploits phenomena of increased radiosensitivity, low-dose hyperradiosensitivity (LDHRS), and inverse dose-rate effect. The purpose of this study was to evaluate LDHRS and the effect of PLDR irradiation in isogenic HNSCC cells with different radiosensitivity. Materials and methods. Cell survival after different irradiation regimens in isogenic parental FaDu and radioresistant FaDu-RR cells was determined by clonogenic assay; post irradiation cell cycle distribution was studied by flow cytometry; the expression of DNA damage signalling genes was assesed by reverse transcription-quantitative PCR. Results. Radioresistant Fadu-RR cells displayed LDHRS and were more sensitive to PLDR irradiation than parental FaDu cells. In both cell lines, cell cycle was arrested in G2/M phase 5 hours after irradiation. It was restored 24 hours after irradiation in parental, but not in the radioresistant cells, which were arrested in G1-phase. DNA damage signalling genes were under-expressed in radioresistant compared to parental cells. Irradiation increased DNA damage signalling gene expression in radioresistant cells, while in parental cells only few genes were under-expressed. Conclusions. We demonstrated LDHRS in isogenic radioresistant cells, but not in the parental cells. Survival of LDHRSpositive radioresistant cells after PLDR was significantly reduced. This reduction in cell survival is associated with variations in DNA damage signalling gene expression observed in response to PLDR most likely through different regulation of cell cycle checkpoints.
Keywords: DNA damage, isogenic cell lines, low dose irradiation, pulsed low dose-rate irradiation, radiosensitivity
Published in DiRROS: 12.07.2024; Views: 143; Downloads: 48
Full text (785,25 KB) |
13. Radiological findings of porcine liver after electrochemotherapy with bleomycinMaja Brložnik, Nina Boc, Gregor Serša, Jan Žmuc, Gorana Gašljević, Alenka Seliškar, Rok Dežman, Ibrahim Edhemović, Nina Milevoj, Tanja Plavec, Vladimira Erjavec, Darja Pavlin, Maša Omerzel, Erik Brecelj, Urša Lampreht Tratar, Bor Kos, Jani Izlakar, Marina Štukelj, Damijan Miklavčič, Maja Čemažar, 2019, original scientific article Published in DiRROS: 05.07.2024; Views: 171; Downloads: 101
Full text (1,17 MB)
This document has many files! More... |
14. Electrochemotherapy with bleomycin of different types of cutaneous tumours in a ferret (Mustela putorius furo)Joško Račnik, Tanja Švara, Marko Zadravec, Mitja Gombač, Maja Čemažar, Gregor Serša, Nataša Tozon, 2018, original scientific article Abstract: Mast cell tumour, sebaceous gland adenoma, and less common squamous papilloma are skin tumours in ferrets (Mustela putorius furo), and early excisional surgery is usually the treatment of choice. The aim of our study was to investigate the effectiveness of electrochemotherapy (ECT), a new, minimally invasive non-surgical method, as first treatment option of different types of ferret skin tumours located on surgically difficult sites. Materials and methods A 5-year-old castrated male ferret with two cutaneous masses, presenting 4 months apart and a 7-year-old spayed female ferret with two cutaneous masses, that appeared simultaneously on two locations are presented. In the first patient, both masses were diagnosed as mast cell tumours, and in the second patient, squamous papilloma and sebaceous adenoma were diagnosed. One session of ECT with bleomycin injected intratumourally was applied in all tumours. Results Complete response (CR) of all tumours was obtained, without recurrence during observation period of 15 months after ECT for first tumour and 11 months after ECT of the tumour located on the right hock in first patient, and 8 months after treatment for the second patient. Conclusions In present study, ECT with bleomycin proved to be safe and effective against different cutaneous tumours in ferrets. Due of good results, low cost and relatively easy procedure, ECT could be the treatment of choice instead of surgery for the selected skin tumours in ferrets.
Published in DiRROS: 11.06.2024; Views: 129; Downloads: 130
Full text (1,59 MB)
This document has many files! More... |
15. Ultrasonographic changes in the liver tumors as indicators of adequate tumor coverage with electric field for effective electrochemotherapyNina Boc, Ibrahim Edhemović, Bor Kos, Maja Marolt-Mušič, Erik Brecelj, Blaž Trotovšek, Maša Omerzel, Mihajlo Djokić, Damijan Miklavčič, Maja Čemažar, Gregor Serša, 2018, original scientific article Abstract: The aim of the study was to characterize ultrasonographic (US) findings during and after electrochemotherapy of liver tumors to determine the actual ablation zone and to verify the coverage of the treated tumor with a sufficiently strong electric field for effective electrochemotherapy. Patients and methods. US findings from two representative patients that describe immediate and delayed tumor changes after electrochemotherapy of colorectal liver metastases are presented. Results. The US findings were interrelated with magnetic resonance imaging (MRI). Electrochemotherapy-treated tumors were exposed to electric pulses based on computational treatment planning. The US findings indicate immediate appearance of hyperechogenic microbubbles along the electrode tracks. Within minutes, the tumors became evenly hyperechogenic, and simultaneously, an oedematous rim was formed presenting as a hypoechogenic formation which persisted for several hours after treatment. The US findings overlapped with computed electric field distribution in the treated tissue, indicating adequate coverage of tumors with sufficiently strong electric field, which may predict an effective treatment outcome. Conclusions. US provides a tool for assessment of appropriate electrode insertion for intraoperative electrochemotherapy of liver tumors and assessment of the appropriate coverage of a tumor with a sufficiently strong electric field and can serve as predictor of the response of tumors.
Keywords: elctrochemotherapy, ultrasound, treatment plan, liver
Published in DiRROS: 11.06.2024; Views: 177; Downloads: 70
Full text (1,07 MB) |
16. Effects of electrochemotherapy with cisplatin and peritumoral IL-12 gene electrotransfer on canine mast cell tumors : a histopathologic and immunohistochemical studyClaudia Salvadori, Tanja Švara, Guido Rocchigiani, Francesca Millanta, Darja Pavlin, Maja Čemažar, Urša Lampreht Tratar, Gregor Serša, Nataša Tozon, Alessandro Poli, 2017, original scientific article Abstract: The study was aimed to characterize tumor response after combined treatment employing electrochemotherapy with IL-12 gene electrotransfer in dogs with spontaneous mast cell tumors (MCT). Materials and methods. Eleven dogs with eleven MCTs were included in the study. Histological changes were investigated in biopsy specimens collected before the treatment (T0), and 4 (T1) and 8 weeks (T2) later. Cellular infiltrates were characterized immunohistochemically by using anti CD3, CD20, Foxp3 (Treg), CD68 and anti MHC-class II antibodies. Proliferation and anti-apoptotic activity of neoplastic cells were assessed using anti Ki-67 and Bcl-2 antibodies. Angiogenetic processes were investigated immunohistochemically by using anti Factor VIII and anti CD31 antibodies and micro vessel density quantification. Results. Histopathological examination of samples at T0 confirmed the diagnosis and the presence of scanty infiltrates consisted mainly of T-lymphocytes and macrophages. At T1 and T2 neoplastic cells were drastically reduced in 7/11 cases, small clusters of neoplastic cells were detected in 3/11 cases and 1/11 cases neoplastic cells were still evident. Proliferation activity of neoplastic cells was significantly reduced at T1 and T2 and expression of anti-apoptotic protein at T1. Microvessel density was drastically reduced in all samples after treatment. The number of T-lymphocytes increased at T1, although not significant, while Treg were significant higher at T1 and macrophages at T2. Conclusions. The combined electrochemotherapy and IL-12 gene electrotransfer effectively induced a cellular response against neoplastic cells characterized mainly by the recruitment of T-lymphocytes and macrophages and a fibrotic proliferation with reduction of microvessels.
Keywords: histopathology, interleukin-12, elektroporation, electrochemotherapy, immune cells
Published in DiRROS: 31.05.2024; Views: 240; Downloads: 119
Full text (956,49 KB) |
17. In vitro and in vivo evaluation of electrochemotherapy with trans-platinum analogue trans-[PtCl2(3-Hmpy)2]Simona Kranjc Brezar, Maja Čemažar, Gregor Serša, Janez Ščančar, Sabina Grabner, 2017, original scientific article Abstract: Background. Cisplatin is used in cancer therapy, but its side effects and acquired resistance to cisplatin have led to the synthesis and evaluation of new platinum compounds. Recently, the synthesized platinum compound trans- [PtCl2(3-Hmpy)2] (3-Hmpy = 3-hydroxymethylpyridine) (compound 2) showed a considerable cytotoxic and antitumour effectiveness. To improve compound 2 cytotoxicity in vitro and antitumour effectiveness in vivo, electroporation was used as drug delivery approach to increase membrane permeability (electrochemotherapy). Materials and methods. In vitro, survival of sarcoma cells with different intrinsic sensitivity to cisplatin (TBLCl2 sensitive, TBLCl2Pt resistant and SA-1 moderately sensitive) was determined using a clonogenic assay after treatment with compound 2 or cisplatin electrochemotherapy. In vivo, the antitumour effectiveness of electrochemotherapy with compound 2 or cisplatin was evaluated using a tumour growth delay assay. In addition, platinum in the serum, tumours and platinum bound to the DNA in the cells were performed using inductively coupled plasma mass spectrometry. Results. In vitro, cell survival after treatment with compound 2 electrochemotherapy was significantly decreased in all tested sarcoma cells with different intrinsic sensitivity to cisplatin (TBLCl2 sensitive, TBLCl2Pt resistant and SA-1 moderately sensitive). However, this effect was less pronounced compared to cisplatin. Interestingly, the enhancement factor (5-fold) of compound 2 cytotoxicity was equal in cisplatin-sensitive TBLCl2 and cisplatin-resistant TBLCl2Pt cells. In vivo, the growth delay of subcutaneous tumours after treatment with compound 2 electrochemotherapy was lower compared to cisplatin. The highest antitumour effectiveness after cisplatin or compound 2 electrochemotherapy was obtained in TBLCl2 tumours, resulting in 67% and 11% of tumour cures, respectively. Compound 2 induced significantly smaller loss of animal body weight compared to cisplatin. Furthermore, platinum amounts in tumours after compound 2 or cisplatin electrochemotherapy were approximately 2-fold higher compared to the drug treatment only, and the same increase of platinum bound to DNA was observed. Conclusions. The obtained results in vitro and in vivo suggest compound 2 as a potential antitumour agent in electrochemotherapy.
Keywords: platinum analogue, cisplatin, elektroporation, electrochemotherapy, 3-Hmpy
Published in DiRROS: 31.05.2024; Views: 304; Downloads: 121
Full text (729,36 KB) |
18. Electrotransfer of plasmid DNA radiosensitizes B16F10 tumors through activation of immune responseMonika Savarin, Urška Kamenšek, Maja Čemažar, Richard Heller, Gregor Serša, 2017, original scientific article Abstract: Tumor irradiation combined with adjuvant treatments, either vascular targeted or immunomodulatory, is under intense investigation. Gene electrotransfer of therapeutic genes is one of these approaches. The aim of this study was to determine, whether gene electrotransfer of plasmid encoding shRNA for silencing endoglin, with vascular targeted effectiveness, can radiosensitize melanoma B16F10 tumors. Materials and methods. The murine melanoma B16F10 tumors, growing on the back of C57Bl/6 mice, were treated by triple gene electrotransfer and irradiation. The antitumor effect was evaluated by determination of tumor growth delay and proportion of tumor free mice. Furthermore, histological analysis of tumors (necrosis, apoptosis, proliferation, vascularization, presence of hypoxia and infiltration of immune cells,) was used to evaluate the therapeutic mechanisms. Results. Gene electrotransfer of plasmid silencing endoglin predominantly indicated vascular targeted effects of the therapy, since significant tumor growth delay and 44% of tumor free mice were obtained. In addition, irradiation had minor effects on radioresistant melanoma, with 11% of mice tumor free. The combined treatment resulted in excellent effectiveness with 88% of mice tumor free, with more than half resistant to secondary tumor challenge, which was observed also with the plasmid devoid of the therapeutic gene. Histological analysis of tumors in the combined treatment group, demonstrated similar mode of action of the gene electrotransfer of plasmid encoding shRNA for silencing endoglin and devoid of it, both through the induction of an immune response. Conclusions. The results of this study indicate that irradiation can in radioresistant melanoma tumors, by release of tumor associated antigens, serve as activator of the immune response, besides directly affecting tumor cells and vasculature. The primed antitumor immune response can be further boosted by gene electrotransfer of plasmid, regardless of presence of the therapeutic gene, which was confirmed by the high radiosensitization, resulting in prolonged tumor growth delay and 89% of tumor free mice that were up to 63% resistant to secondary challenge of tumor. In addition, gene electrotransfer of therapeutic plasmid for silencing endoglin has also a direct effect on tumor vasculature and tumors cells; however in combination with radiotherapy this effect was masked by pronounced immune response.
Keywords: gene therapy, electrotransfer, plasmid, irradiation, immune response, melanoma
Published in DiRROS: 24.05.2024; Views: 292; Downloads: 210
Full text (1,13 MB) |
19. |
20. Electrochemotherapy by pulsed electromagnetic field treatment (PEMF) in mouse melanoma B16F10 in vivoSimona Kranjc Brezar, Matej Kranjc, Janez Ščančar, Jure Jelenc, Gregor Serša, Damijan Miklavčič, 2016, original scientific article Keywords: pulsed electromagnetic field, bipolar pulses, contactless electroporation, CDDP, electrochemotherapy, mouse melanoma
Published in DiRROS: 09.05.2024; Views: 281; Downloads: 172
Full text (721,66 KB)
This document has many files! More... |
