41. MRI macromolecular contrast agents as indicators of changed tumor blood flowTeodora Ivanuša, Katarina Beravs, Maja Čemažar, Vladimir Jevtič, Franci Demšar, Gregor Serša, 2001, original scientific article Abstract: 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.
Published in DiRROS: 25.01.2024; Views: 156; Downloads: 35
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42. First experience with a novel luminescence-based optical sensor for measurement of oxygenation in tumorsTomaž Jarm, Hotimir Lešničar, Gregor Serša, Damijan Miklavčič, 2001, original scientific article Abstract: 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.
Keywords: sarcoma experimental, blood supply, laser-doppler flowmetry, oxygen, luminiscence
Published in DiRROS: 25.01.2024; Views: 153; Downloads: 39
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43. Electrochemotherapy with cisplatin of breast cancer tumor modules in a male patientMartina Reberšek, Tanja Čufer, Zvonimir Rudolf, Gregor Serša, 2000, original scientific article Abstract: 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.
Published in DiRROS: 25.01.2024; Views: 139; Downloads: 35
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44. Antitumor effectiveness of bleomycin on SA-1 tumor after pretreatment with vinblastineMaja Čemažar, Marija Auersperg, Gregor Serša, 2000, original scientific article Abstract: In our previous study, vinblastine (VLB) was shown to increase the plasma membrane fluidity. This effect of VLB might be exploited for better transport of drugs through the plasma membrane. The aim of the present study was to determine whether pretreatment with VLB can increase the cytotoxic effect of BLM on intraperitoneal SA-1 tumors in mice. Materials and methods. BLM and VLBwere used as single agents or in various combinations, i.e. BLM injected 24h before VLB or vice-versa, VLB injected 24 h before BLM. Cell and animal survival together with DNA histograms were the end-points used to determine the effect of these combined treatments. Results. Both drugs, either as singletreatment or in different combined therapy schedules reduced significantly the number of cells in peritoneal lavage, compared to control, saline treated animals. The combination of VLB, followed by BLM after 24 h reduced significantly the number of cells in peritoneal lavage, compared to the treatment in which BLM was followed by VLB or to the treatment with singledrugs alone. Median survival time of mice treated with VLB alone, BLM alone and combination of both drugs was significantly prolonged compared to the control untreated mice. When VLB and BLM were combined, both treatment combinations were more effective than monochemotherapies with VLB or BLM. The best results were obtained when VLB was followed by BLM after 24 h. The DNA histogram of cells treated with VLB showed a decreased number of cells in S phase and an increased number of cells with DNA values greater than in G2M compartment compared to the control untreated cells. BLM in the dosage used inthese experiments did not affect the progression of cells through cell cycle. Both combinations of VLB and BLM produced similar cell kinetic effect as VLB alone. Conclusion. (Abstract truncated at 2000 characters.)
Published in DiRROS: 23.01.2024; Views: 135; Downloads: 30
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45. Comparison of colorimetric MTT and clonogenic assays for irradiation and cisplatin treatment on murine fibrosarcoma SA-1 cellsMaja Čemažar, Darja Marolt, Mira Lavrič, Gregor Serša, 1999, original scientific article Abstract: Background. The aim of our study was to determine the relationship between cell survival of SA-1 tumor cells measured by clonogenic assay and MTT assay after irradiation and cisplatin treatment. Materials and methods. Survival of SA-1 cells was measured after irradiation (2-8 Gy) and cisplatin treatment (0.05-0.5 u g/ml) by clonogenic assay performed 7 days after treatment, and byMTT assay performed on day 3, 4, 5, and 7 after the treatment. Results. The results showed good correlation between MTT assay and clonogenic assay for irradiation doses below 4 Gy. For higher doses good correlation between MTT and clonogenic assay was determined only when MTT assay was performed on day 5and 7 after the treatment. In the case of cisplatin treatment, similar pattern was observed, good correlation between IC50 values for MTT and clonogenic assay was found when MTT assay was performed on day 5 and 7 after the treatment. Conclusion. Results of our study confirmed the results of previous studies addressing this topic and further support the use of MTT testas an alternative test for clonogenic test as a predictive assay of tumourresponse to the radio or chemotherapy.
Published in DiRROS: 22.01.2024; Views: 158; Downloads: 33
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46. Adenocarcinoma skin metastases treated by electrochemotherapy with cisplatin combined with radiationGregor Serša, Maja Čemažar, Zvonimir Rudolf, Albert-Peter Fras, 1999, original scientific article Abstract: Background. The aim of this study was to determine the interaction between electrochemotherapy as a means of facilitated cisplatin delivery into the cells and irradiation of adenocarcinoma skin metastases. Case report. A patient with progressive disease presenting skin metastases of tubal dedifferentiated pappilary adenocarcinoma was enrolled in the study. Skin metastases were treated by electrochemotherapy with intratumoral injection of cisplatin. Its antitumor effectiveness was compared to that of combined treatment of irradiation with electrochemotherapy. After a two week observation time, the response to treatment was comparable between the electrochemotherapy and electrochemotherapy combined with irradiation. Both ofthese treatments were more effective than irradiation alone. Furthermore, antitumor effectiveness of the combined electrochemo- and radiotherapy was found to be quicker than that of electrochemotherapy alone. Comment. This study shows that electrochemotherapy with cisplatin is also effective in the treatment of adenocarcinoma skin metastases. Inspite of the short observation time, positive interaction between radiotherapy and electrochemotherapy with cisplatin was found.
Published in DiRROS: 22.01.2024; Views: 140; Downloads: 34
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47. Cryosurgery combined with radiotherapy of tumors in miceAlbert-Peter Fras, Simona Kranjc Brezar, Maja Čemažar, Gregor Serša, 1999, original scientific article Abstract: Tlle aim of this study zuas to determine antitumor effectiveness of cryosurgery alone and in comhination with radiotherapy. Cryosurgery of subcutaneous fibrosarcoma SA-1 tumors in A/J mice was moderately effective trcatmcnt. Tumor growth delay was 10.3 * 3.8 days after 5 minute treatment with nitrogen filled cryo-prohe. Shorter treatment times induced less, but dose dependent antitumor effect. In combined treat- ment, tumors were either first treated by cryosurgery for 3 minutes and then locally irradiated with 10Gy for 5 minutes, or irradiated first and thereafter treated by cryosurgery.The antitumor effectiveness of com- bined treatrnent was sequence dependent; the irradiation of tumors before cryosurgery resulted in better antitumor effect than the irradiation after cryosurgery. These results indicate that radiosensitization may not be always expected, in spite of some reports demonstrating that cryosurgery may have radiosensitizing effect in vivo, and that some other mechanisms may be involved contributing to radiationdamage when cryosurgery follows irradiation.
Published in DiRROS: 22.01.2024; Views: 149; Downloads: 40
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48. Plasma membrane fluidity alterations in cancerous tissuesMarjeta Šentjurc, Mihael Sok, Gregor Serša, 1998, original scientific article Abstract: Plasma membrane is a heterogeneous structure with several coexisting domains having different fluidity characteristics. It plays an important role in the control of cell growth, differentiation and transformation. Fluidity of the whole plasma membrane reflects the ordering and dynamics of phospholipid acyl chains in specific membrane domains, as well as the fraction of each domain inthe membrane. Changes in the membrane fluidity affect processes on the membrane such as transport, enzyme activities and expression of the redeptors.In this paper we present results of our recent electron paramagneticresonance (EPR) studies of plasma membrane fluidity characteristics, which take into account heterogeneous nature of the plasma membrane, By the computer simulation of the EPR spectra line-shapes, the number of coexisting domains in the plasma membrane, their relative portion inthe membrane as well as the ordering and dynamics of each domain be determined. Therefore, we could distinguish the contribution of the relative portion of each domain from the contribution of fulidity alterations in the domain to the entire fluidity changes in the membrane. Two examples will be discussed: membrane fluidity characteristics of excised lung tumor tissues andinfluence of microtubule depolymerizing agent vinblastine on membrane fluidity of vinblastine sensitive and resistant HeLa cells.
Published in DiRROS: 19.01.2024; Views: 136; Downloads: 33
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