11. Influence of hydralazine on interstitial fluid pressure in experimental tumors - a preliminary study : Vpliv hydralazina na tlak medcelične tekočine v poskusnih tumorjihBlaž Podobnik, Damijan Miklavčič, 2000, original scientific article Abstract: Background. Interstitial fluid pressure (IFP) has been recognised as the most important obstacle in macromolecular drug delivery to solid tumors. Our interest was to reduce differentialy tumor IFP with respect to IFP in surrounding and normal tissues in order to increase drug delivery to tumors aswell to increase tumor blood flow and potentialy tumor tissue oxygenation. In this preliminary study we used hydralazine, a longacting arterial vasodilator. Materials and methods. Measurements of interstitial fluid pressure were performed in vivo on CBA mice bearing SAF tumors using wick-in-needle technigue. Altogether eleven measurements were obtained on different animals with tumors of different size. Results. IFP in tumors after hydralazine administration was significantly lower than initial values in corresponding tumors. On average tumor IFP decreased for 33 % from initial value. On the contrary, no change in IFP in normal tissue was observed after hydralazine administration. Also, after injection of physiological saline instead of hydralazine there was no change in IFP neither in tumors nor in muscle. The results of our preliminary study on the effect of hydralazine on IFP in SAF tumor model is in accordance to previously reported studies. The decrease in tumor IFP was only observed in tumors, but not in muscle and surrounding subcutis. Conclusion. Hydralazine is a vasodilator which is capable of decreasing tumor IFP, reproducibly and with favorably long lasting dynamics.
Keywords: sarcoma, experimental drug therapy, hydralazine, extracellular space, interstitial fluid pressure, manometry
Published in DiRROS: 23.01.2024; Views: 212; Downloads: 55
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14. Electrochemotherapy with bleomycin : The first clinical experience in malignant melanoma patientsZvonimir Rudolf, Borut Štabuc, Maja Čemažar, Damijan Miklavčič, Lojze Vodovnik, Gregor Serša, 1995, original scientific article Keywords: melanoma therapy, bleomycin, electric stimulation therapy
Published in DiRROS: 15.01.2024; Views: 213; Downloads: 48
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15. Improved therapeutic effect of electrochemotherapy with cisplatin by intratumoral drug administration and changing of electrode orientation for electropermeabilization on EAT tumor model in miceMaja Čemažar, Damijan Miklavčič, Lojze Vodovnik, Tomaž Jarm, Zvonimir Rudolf, Borut Štabuc, Tanja Čufer, Gregor Serša, 1995, original scientific article Keywords: neoplasmas, experimental therapy, cisplatin, electric stimulation therapy, cell membrane permeability
Published in DiRROS: 15.01.2024; Views: 181; Downloads: 50
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17. Elektrokemoterapija malignega melanomaGregor Serša, Borut Štabuc, Tanja Čufer, Boris Jančar, Damijan Miklavčič, Maja Čemažar, Zvonimir Rudolf, 1999, published scientific conference contribution Keywords: melanom, zdravljenje, bleomicin, cisplatin, električna stimulacija, elektrokemoterapija, elektroporacija, melanoma therapy, bleomycin, cisplatin, electric stimulation therapy, electrochemotherapy, electroporation
Published in DiRROS: 27.11.2023; Views: 201; Downloads: 67
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18. Gene electrotransfer of IL-2 and IL-12 plasmids effectively eradicated murine B16.F10 melanomaTilen Komel, Maša Omerzel, Simona Kranjc Brezar, Mariangela De Robertis, M. Mastrodonato, G. Scillitani, G. Pesole, Emanuella Signori, Gregor Serša, Maja Čemažar, 2021, original scientific article Abstract: Gene therapy has become an important approach for treating cancer, and electroporation represents a technology for introducing therapeutic genes into a cell. An example of cancer gene therapy relying on gene electrotransfer is the use of immunomodulatory cytokines, such as interleukin 2 (IL-2) and 12 (IL-12), which directly stimulate immune cells at the tumour site. The aim of our study was to determine the effects of gene electrotransfer with two plasmids encoding IL-2 and IL-12 in vitro and in vivo. Two different pulse protocols, known as EP1 (600 V/cm, 5 ms, 1 Hz, 8 pulses) and EP2 (1300 V/cm, 100 %s, 1 Hz, 8 pulses), were assessed in vitro for application in subsequent in vivo experiments. In the in vivo experiment, gene electrotransfer of pIL-2 and pIL-12 using the EP1 protocol was performed in B16.F10 murine melanoma. Combined treatment of tumours using pIL2 and pIL12 induced significant tumour growth delay and 71% complete tumour regression. Furthermore, in tumours coexpressing IL-2 and IL-12, increased accumulation of dendritic cells and M1 macrophages was obtained along with the activation of proinflammatory signals, resulting in CD4 + and CD8 + T-lymphocyte recruitment and immune memory development in the mice. In conclusion, we demonstrated high antitumour efficacy of combined IL-2 and IL-12 gene electrotransfer protocols in low-immunogenicity murine B16.F10 melanoma.
Keywords: gene therapy, gene electrotransfer, IL-12, immunotherapy, melanoma
Published in DiRROS: 23.09.2022; Views: 639; Downloads: 188
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19. Availability and costs of medicines for the treatment of tuberculosis in EuropeGunar Günther, Lorenzo Guglielmetti, Claude Leu, Christoph Lange, Frank van Leth, 2022, review article Abstract: Objectives. To evaluate the access to comprehensive diagnostics and novel anti-tuberculosis medicines in European countries. Methods. We investigated access to genotypic and phenotypic M. tuberculosis drug susceptibility testing, availability of anti-tuberculosis drugs and calculated cost of drugs and treatment regimens at major tuberculosis treatment centers in countries of the World Health Organization (WHO) European region where rates of drug-resistant tuberculosis are highest among all WHO regions. Results are stratified by middle-income and high-income countries. Results. Overall, 43 treatment centers in 43 countries participated in the study. For WHO Group A drugs, the frequency of countries with availability of phenotypic drug susceptibility testing was as follows: 30/40 (75%) for levofloxacin, 33/40 (82%) for moxifloxacin, 19/40 (48%) for bedaquiline and 29/40 (72%) for linezolid, respectively. Overall, 36/43 (84%) and 24/43 (56%) of countries had access to bedaquiline and delamanid, while only 6/43 (14%) had access to rifapentine. Treatment of patients with extensively drug-resistant tuberculosis with a regimen including a carbapenem was only available in 17/43 (40%) of the countries. Median cost of regimens for drug-susceptible tuberculosis, multidrug-resistant/rifampicin-resistant tuberculosis (shorter regimen, including bedaquiline for six months) and extensively drug-resistant tuberculosis (including bedaquiline, delamanid and a carbapenem) were € 44 (min-max € 15-152), € 764 (min-max € 542-15152) and € 8709 (min-max € 7965-11759) in middle-income countries (n=12), and € 280 (min-max-€78-1084), € 29765 (min-max 11116-40584), € 217591 (min-max € 82827-320146) in high-income countries (n=29). Conclusion. In countries of the WHO Europe Region there is a widespread lack of drug susceptibility testing capacity to new and re-purposed anti-tuberculosis drugs, lack of access to essential medications in several countries and high treatment cost for drug-resistant tuberculosis.
Keywords: tuberculosis - drug therapy, Mycobacterium tuberculosis - drug therapy, health care costs - drug therapy, Europe
Published in DiRROS: 31.08.2022; Views: 747; Downloads: 153
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20. Real-world experience with capmatinib in MET exon 14-mutated non-small cell lung cancer (RECAP) : a retrospective analysis from an early access programOliver Illini, Hannah Fabikan, Aurélie Swalduz, Anders Vikström, Dagmar Krenbek, Michael Schumacher, Elizabeth Dudnik, Michael Studnicka, Ronny Öhman, Robert Wurm, Tanja Čufer, Katja Mohorčič, Maximilian J Hochmair, 2022, original scientific article Abstract: Background: Patients with non-small cell lung cancer (NSCLC) presenting with mesenchymal–epithelial transition (MET) exon 14 skipping mutation have an unfavorable prognosis with standard treatments. Capmatinib is a selective MET inhibitor, which showed promising efficacy in this patient population in early trials. Methods: We performed a retrospective, international, multicenter efficacy and safety analysis in patients with NSCLC treated with capmatinib in an early access program between March 2019 and December 2021. Results: Data from 81 patients with advanced MET exon 14 mutated NSCLC treated with capmatinib in first- or later-line therapy were analyzed. Median age was 77years (range, 48–91), 56% were women, 86% had stage IV disease, and 27% had brain metastases. For all patients, the objective response rate (ORR) to capmatinib was 58% (95% CI, 47–69), whereas it was 68% (95% CI, 50–82) in treatment-naïve and 50% (95% CI, 35–65) in pretreated patients. The median progression-free survival was 9.5months (95% CI, 4.7–14.3), whereas it was 10.6months (95% CI, 5.5–15.7) in first-line and 9.1months (95% CI, 3.1–15.1) in pretreated patients. After a median follow-up of 11.0months, the median overall survival was 18.2 months (95% CI, 13.2–23.1). In patients with measurable brain metastases (n=11), the intracranial ORR was 46% (95% CI, 17–77). Capmatinib showed a manageable safety profile. Grade⩾3 treatment-related adverse events included peripheral edema (13%), elevated creatinine (4%), and elevated liver enzymes (3%). Conclusion: In patients with MET exon 14 skipping mutation, capmatinib showed durable systemic and intracranial efficacy and a manageable safety profile. This analysis confirms previously reported phase II data in a real-world setting.
Keywords: non-small cell lung carcinoma -- drug therapy -- genetics, molecular targeted therapy, real-world data, capmatinib, targeted therapy
Published in DiRROS: 24.06.2022; Views: 770; Downloads: 573
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