21. Targeted gene therapy in radiotherapyUrška Kamenšek, Gregor Serša, 2008, pregledni znanstveni članek Povzetek: The dramatic pace in development of gene therapy over the past decades has made it a realistic alternative for the treatment of cancer. Radiotherapy, on the other hand, is one of the most commonly used and well established cancer treatment modalities. The latest improvements in the physical targeting ability of radiotherapy and understanding of the molecular mechanism involved in the cellular response to ionizing radiation have presented an opportunity to combine radiotherapy with gene therapy. This review article will focus on gene therapy strategies that can be used to enhance the effectiveness of radiotherapy, with an emphasis on transcriptional targeting approaches.
Objavljeno v DiRROS: 07.03.2024; Ogledov: 91; Prenosov: 29
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23. Electrochemotherapy of tumoursGregor Serša, Maja Čemažar, Damijan Miklavčič, Zvonimir Rudolf, 2006, pregledni znanstveni članek Povzetek: Electroehemotherapy consists of chemotherapy followed by local application of electrie pulses to the tumour to increase drug delivery into cells. Drug uptake can be inereased by electroporation for only those drugs whose transport through the plasma membrane is impeded. Among many drugs that have been tested so far, only bleomycin and cisplatin found their way from preclinical testing to clinical trials. In vitro studies demonstrated several fold inerease of their cytotoxicity after electroporation of cells. In vivo, electroporation of tumours after local or systemic administration of either ofthe drugs, i.e. electrochemotherapy, proved to be an effective antitumour treatment. In preclinical studies on several tumour models, electrochemotherapy either with bleomycin or cisplatin was elaborated and parameters for effective local tumour control were determined. In veterinary medicine, electrochemotherapy also proved to be effective in the treatment of primary tumours in cats, dogs and horses. In human clinical studies, electrochemotherapy was performed on the patients with progressive disease andaccessible tumour nodules of different malignancies. All clinical studies demonstrated that electrochemotherapy is an effective treatment for local tumour control in cancer patients.
Objavljeno v DiRROS: 15.02.2024; Ogledov: 137; Prenosov: 40
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24. Schedule-dependency of doxorubicin and vinblastine in EAT tumours in miceMarija Auersperg, Ana Pogačnik, Veronika Kloboves-Prevodnik, Gregor Serša, Maja Čemažar, 2006, izvirni znanstveni članek Povzetek: Background. Antitumour schedule-dependency of the doxorubicin and vinblastine combination was explored. Materials and methods. Intraperitoneal Ehrlich ascites tumours (EAT) syngeneic to CBA mice were treated with vinblastine ar doxorubicin alone, or in combined treatment schedules. Results. Combinations of doxorubicin and vinblasfine administered at 48-h, but not at 24-h interval,regardless of the sequence of drugs, significantly reduced the numberof tumour cells in the ascites in corrtparison with all other treatments. In the combined treatment schedules, the predominant morphologicalchanges as well as DNA distribution pattern were dependent on thefirst drug applied. Regardless of the sequence of the drugs, median survival times of animals did not significantly differ between the treatment groups. Conclusions. The effect of combination of vinblastine and doxorubicin is schedule-dependent. The time interval, but not the sequence of drugs seems to be crucial for the observed effect. The data from preclinical studies are important for planning combined treatment schedules in clinical setting.
Objavljeno v DiRROS: 15.02.2024; Ogledov: 103; Prenosov: 23
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25. Effect of electroporation on radiosensitization with cisplatin in two cell lines with different chemo- and radiosensitivitySimona Kranjc Brezar, Maja Čemažar, Alenka Grošel, Živa Pipan Tkalec, Gregor Serša, 2003, izvirni znanstveni članek Povzetek: Aim. Radiosensitization with cisplatin can be enhanced by electroporation of cells and tumours. The aim of this study was to extend our previous studies ontwo carcinoma tumour models with different chemo-and radiosensitivity in order to evaluate whether this treatment is effective also on less chemo-and radiosensitive tumour cells. Materials and methods. This in vitro study was performed on carcinoma SCK and EAT-E cells. The cytotoxicity of three-modalitytreatment consisting of cisplatin, electroporation and irradiation was determined by the clonogenic assay. Results. The radiosensitizing effect of cisplatin on the two cell lines was greatly enhanced by electroporation. By this combined treatment, less chemo and radiosensitive EAT-E cells were rendered as sensitive as more chemo and radiosensitive SCK cells. Conclusion. The enhancement of cisplatin-induced radiosensitization of cells by electroporation could be beneficially used in the treatment of intrinsically less chemo- and radiosensitive tumours.
Objavljeno v DiRROS: 06.02.2024; Ogledov: 131; Prenosov: 27
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26. Tumor blood flow modifying effects of electrochemotherapy : a potential vascular targeted mechanismGregor Serša, Maja Čemažar, Damijan Miklavčič, 2003, izvirni znanstveni članek Povzetek: Background. The aim of this study was to determine the tumor blood flow modifying, and potential vascular targeted effect of electrochemotherapy with bleomycin or cisplatin. Materials and methods. Electrochemotherapy was performed by application of short intense electric pulses to the tumors after systemic administration of bleomycin or cisplatin. Evaluated were antitumor effectiveness of electrochemotherapy by tumor measurement, tumor blood flow modifying effect by Patent blue staining technique, and sensitivity of endothelial and tumor cells to the drugs and electrochemotherapy by clonogenicity assay. Results. Electrochemotherapy was effective in treatment of SA-1 tumors in A/J mice resulting in substantial tumor growth delay and also tumor cures. Tumor blood flow reduction following electrochemotherapy correlated well with its antitumor effectiveness. Virtually complete shut downof the tumor blood flow was observed already at 24 h after electrochemotherapy with bleomycin whereas only 50% reduction was observed after electrochemotherapy with cisplatin. Sensitivity of human endothelial HMEC-1 cells to electrochemotherapy suggests a vascular targeted effect for electrochemotherapy in vivo with bleomycin as well as with cisplatin. Conclusion. These results show that in addition to direct electroporation of tumor cells, other vascular targeted mechanisms are involved in electrochemotherapy with bleomycin or cisplatin, potentially mediated by tumorblood flow reduction, and enhanced tumor cell death as a result of endothelial damage by electrochemotherapy.
Objavljeno v DiRROS: 06.02.2024; Ogledov: 123; Prenosov: 28
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27. Effects of 5-Gy irradiation on fertility and mating behaviour of Nezara viridula (Heteroptera: Pentatomidae)Alenka Žunič Kosi, Andrej Čokl, Gregor Serša, 2002, izvirni znanstveni članek Povzetek: Background. The polyphagous and cosmopolitan species Nezara viridula is one ofthe most important insect pests. The sterile insect technique (SIT) is a pest control strategy that involves sterilising males by exposing them to ionising radiation. Sterile males, released into wild population, mate with females, but eggs are not fertilised and the population gradually declines. Exposing insects to radiation during their growth stage might require lower sterilising dose. The aim of our study was to test whether 5-Gy irradiation of5th instar nymphs significantly affects: (1) moulting and further development of the irradiated nymphs, (2) the male's and female's reproduetivesystem and (3) the mating competitiveness of treated males, with special focus on vibrational communication. Methods: The 5th instar nymphs were irradiated with 5 Gy using X ray generator and monitored daily. Results: The observed effects of irradiation were: prolonged moulting increased mortality during development and during the first day of adult life, decreasedmales to females ratio, decreased fecundity, egg production, proportion of fertile eggs and progeny survival. The reaction of a male to stimulation with the model female calling song was tested. The irradiated and non-irradiated males responded to stimulation with emission of the eourtship song (MCrS). Temporal parameters of MCrS emitted by non-irradiated males differed when compared with those of irradiated ones. Conclusions: The 5-Gy irradiation of 5th instar nymphs did not affect mating behaviour. However since the irradiation during growth stage decreased the fertility and fecundity of emerged adults, this technique, in combination with certain othersuppression teehniques, could be a successful control strategy for management of Nezara viridula. On the other hand observed effects on moulting and further development of the irradiated nymphs could decrease the efficiencyand application of this strategy.
Objavljeno v DiRROS: 31.01.2024; Ogledov: 143; Prenosov: 33
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28. MRI macromolecular contrast agents as indicators of changed tumor blood flowTeodora Ivanuša, Katarina Beravs, Maja Čemažar, Vladimir Jevtič, Franci Demšar, Gregor Serša, 2001, izvirni znanstveni članek Povzetek: Background. A rapid mapping technique derived from dynamic contrast enhanced MRI data was used to identify and characterize reduction of blood flow in fibrosarcoma SA-1 tumors treated either by application of electric pulses or vinblastine. Materials and methods. Tissue permeability surface area product (PS) and fractional blood volume (BV) were calculated on a pixel-by-pixel basis using dynamic MRI intensity data after administration of gadomer - 17 orpolylysine-Gd-DTPA; prototypic macromolecular contrast agents designed for blood pool enhancement. PS and BV values of untreated tumors were compared to those of tumors treated by local application of 8 electric pulses (amplitude/distance ratio, 1300 V/cm; duration, 100 us, frequency, 1 Hz) percutaneously to the tumor or by systemic administration of vinblastine (2.5 mg/kg). Results. Both treatments transiently, but significantly reduced tumor blood flow, application of electric pulses to the tumors being by 40% more effective in reducing tumor blood flow than systemic administration of vinblastine. PS and BV values derived with polylysine-Gd-DTPA-enhanced MRI were lower compared to those with gadomer-17, due to larger molecular size. Interestingly, Gd-DTPA-enhanced MRI did not show any significant changes of PSand BV between untreated and treated tumors. Conclusion. This study demonstrates that dynamic contrast enhanced MRI can be effectively used to qualitatively monitor tumor blood flow, and quantitatively by means of BV and PS.
Objavljeno v DiRROS: 25.01.2024; Ogledov: 157; Prenosov: 35
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29. First experience with a novel luminescence-based optical sensor for measurement of oxygenation in tumorsTomaž Jarm, Hotimir Lešničar, Gregor Serša, Damijan Miklavčič, 2001, izvirni znanstveni članek Povzetek: Background. The purpose of this preliminary study was to evaluate a novel luminescence-based fiber-optic sensor (OxyLite system) for the measurement of partial pressure of oxygen (pO2) in tumors and for the detection of changes inpO2 as a function of time. The new method was used simultaneously with the laser Doppler flowmetry method for the measurement of relative tissue perfusion. Materials and methods. Blood perfusion and pO2 were measured continuously via fiber-optic sensors inserted into SA-1 tumors in anesthetizedAžJ mice. The changes in blood flow and oxygenation of tumors wereinduced by transient changes of the parameters of anesthesia and by injection of a vasoactive drug hydralazine. Results. Both optical methods usedin the study successfully detected the induced changes in blood flow and pO2. The measurements of pO2 were well correlated with measurements of microcirculatory blood perfusion. In the majority of pO2 measurements, we observed an unexpected behavior of the signal during the stabilization processimmediately after the insertion of the probe into tumor. This behaviourof the pO2 signal was most probably caused by local tissue damage induced by the insertion of the probe. Conclusion. The novel luminescence-based optical oximetry can reliably detect local pO2 changes in tumors as a function of time but some aspects of prolonged pO2 measurement by this method require further investigation.
Ključne besede: sarcoma experimental, blood supply, laser-doppler flowmetry, oxygen, luminiscence
Objavljeno v DiRROS: 25.01.2024; Ogledov: 153; Prenosov: 39
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30. Electrochemotherapy with cisplatin of breast cancer tumor modules in a male patientMartina Reberšek, Tanja Čufer, Zvonimir Rudolf, Gregor Serša, 2000, izvirni znanstveni članek Povzetek: Background. The metastases of breast cancer in a male patient were treated with electrochemotherapy by intratumoral injection of cisplatin. Electrochemotherapy is chemotherapy with the subsequent local application of electric pulses to the tumor nodules in order to increase drug delivery into the cells. Case report. Cutaneous metastases of breast cancer were treated with the intratumoral administration of cisplatin and by 8 electric pulses (1300 V/cm) applied a minute later to each cutaneous metastasis. The treatmentresulted in complete response of two electrochemotherapy treated cutaneous metastases and partial response of the third metastasis. In cutaneous metastases treated with intratumoral administartion of cisplatin without electric pulses, only partial response was obtained. Conclusion. This study confirms that electrochemotherapy with cisplatin is effective in the treatment of breast cancer metastases, too, as it was already proved for electrochemotherapy with bleomycin.
Objavljeno v DiRROS: 25.01.2024; Ogledov: 139; Prenosov: 35
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