Biomedical subjects

D Miklavcic

Publications and source records attributed to D Miklavcic.

42 records · Page 3Linked to original sources

PubMed1992

Anti-tumor effect of electrotherapy alone or in combination with interleukin-2 in mice with sarcoma and melanoma tumors.

Electrotherapy with direct current (DC) was performed on two murine tumor models, fibrosarcoma SA-1 and melanoma B16. Three Pt/Ir cathodes were inserted directly into the subcutaneous tumors and two anodes subcutaneously in the vicinity of the tumor. Significant tumor growth delay was achieved after electrotherapy and was dependent on DC intensity (0.6, 1.0, 1.4 and 1.8 mA). Melanoma B16 tumors were more sensitive to electrotherapy than SA-1 tumors. In order to enhance the antitumor effect of electrotherapy, combined treatment with interleukin-2 (IL-2) was performed. When both therapies were combined significant tumor growth delay and also higher curability rate was achieved. The results imply that electrotherapy can be an effective antitumor therapy and that the effects can be enhanced with additional IL-2 therapy.

Animals↗

PubMed1990

Inhibition of SA-1 tumor growth in mice by human leukocyte interferon alpha combined with low-level direct current.

A preliminary study of the antitumor effect of partially purified human interferon alpha (IFN-alpha) and low-level direct current (DC) was carried out using a murine subcutaneous SA-1 experimental tumor model. Tumor-bearing animals were treated with 5 x 10(4) IU IFN-alpha peritumorally, or with 0.6 mA DC current for 15 minutes daily, for 6 consecutive days. Antitumor effect was manifested 2 days after the beginning of each treatment modality. Combined treatment with DC current applied immediately after IFN-alpha application was more effective than IFN-alpha treatment alone (P less than 0.005), but not significantly better than DC current treatment (P less than 0.5). The results indicate that the combined treatment with IFN-alpha and DC current can be effective in tumor therapy; however, further work is required to determine optimal scheduling.

Animals↗

PubMedDate not supplied

An algorithm for synchronization of in vivo electroporation with ECG.

The combined treatment of tumours in which delivery of a chemotherapeutic agent is followed by high voltage electroporation pulses has been termed electrochemotherapy. The electrochemotherapy of tumours located relatively close to the heart muscle can lead to fibrillation of the heart, especially if electroporation pulses are delivered in the vulnerable period of the heart or in coincidence with heart arrhythmias. We built an electroporation pulse delivery algorithm that enables safer use of electrochemotherapy. The algorithm is designed to deliver pulses outside the vulnerable period and to prevent pulses from being generated in the presence of heart arrhythmias. We evaluated the algorithm's performance using records of the Long-Term ST Database, thus simulating real-world conditions. The results of the evaluation, a sensitivity of 91.751%, a positive predictivity of 100.000% and a delivery error rate of 8.268% for electroporation pulse delivery (medians), suggest that the algorithm is accurate and appropriate for application in electrochemotherapy of tumours regardless of tumour location.

Algorithms↗

PubMedDate not supplied

Tumor blood flow modifying effect of electrochemotherapy with bleomycin.

BACKGROUND: Electrochemotherapy combines administration of the chemotherapeutic drug, followed by application of electric pulses in order to increase drug delivery into the cells. The aim of this study was to determine the tumor blood flow modifying effect of electrochemotherapy with bleomycin and correlate it with its antitumor effectiveness and extent of tumor necrosis. MATERIALS AND METHODS: Electrochemotherapy of SA-1 subcutaneous tumors in A/J mice was performed by application of electric pulses to the tumors, following administration of bleomycin, and antitumor effectiveness determined by tumor growth delay and tumor cures as well as extent of tumor necrosis. Tumor blood modifying effect of therapy was evaluated by Patent blue staining technique and 86RbCl extraction technique. RESULTS: A good correlation of the two methods evaluating tumor blood flow, Patent blue staining and the established 86RbCl extraction technique was found (r = 0.944). Electrochemotherapy resulted in complete and permanent shut down of tumor blood flow within 12 hours, which lasted for at least 5 days. The results on tumor blood flow reduction correlated well with the good antitumor effectiveness of electrochemotherapy and with the extent of the necrosis in the tumors. CONCLUSIONS: The results indicate that Patent blue staining technique is a simple and reliable method for estimation of tumor blood flow and that antitumor effectiveness of electrochemotherapy with bleomycin could be partly attributed to its tumor blood modifying and anti-vascular effect.

Animals↗

PubMedDate not supplied

Effect of hydralazine on interstitial fluid pressure in experimental tumours and in normal tissue.

Interstitial fluid pressure (IFP) has been recognised as the most important obstacle in macromolecular drug delivery to solid tumours. The aim of our study was to measure the IFP simultaneously in tumour and in muscle or in subcutis and to determine whether injection of hydralazine reduces differentially tumour IFP with respect to IFP in surrounding and normal tissues. In addition, it was of interest whether the decrease in IFP due to hydralazine depends on tumour volume and/or on initial IFP. Measurements of IFP were performed by means of the wick-in-needle technique and they were obtained on tumours of different size. In both tumour models, hydralazine significantly reduced the pretreatment IFP level. On average IFP decreased by 31% and 14% from the initial value in SAF and LPB tumours, respectively. On the contrary, hydralazine did not decrease IFP in normal tissue. Injection of NaCl solution instead of hydralazine had no effect on IFP either in tumours or in subcutis/muscle. The results of our study on the effect of hydralazine on IFP in SAF and LPB tumour model are in accordance to previously reported studies. The initial IFP in tumour is positively-correlated with the tumour size, while the decrease in the tumour IFP is independent of the initial IFP value. In addition, the decrease in tumour IFP is not correlated to tumour volume.

Animals↗

PubMedDate not supplied

Electrochemotherapy with cisplatin in the treatment of tumor cells resistant to cisplatin.

The aim of our study was to investigate the role of electroporation in the treatment of cisplatin resistant tumor cells in vitro. For this purpose we used well characterized human ovarian carcinoma IGROV I cells and their resistant subclone IGROV 1/DDP. The cells were either continuously exposed to cisplatin or treated with electrochemotherapy (exposure time: 5 minutes). After chronic exposure of cells to cisplatin, IGROV 1/DDP cells exhibited 8-fold resistance to cisplatin. Cisplatin cytotoxicity was greatly potentiated by treatment with electric pulses in both cell lines. However, the IGROV 1/DDP cells still exhibited a 50-fold resistance. Our results demonstrate that electroporation treatment potentiates cytotoxicity in both human ovarian carcinoma IGROV 1 cells as well as in their resistant subclone IGROV 1/DDP.

Cell Membrane Permeability↗