Oncolytic virotherapy is an emerging immunotherapeutic modality for cancer treatment. Oncolytic viruses with genetic modifications can further enhance the oncolytic effects on tumor cells and stimulate antitumor immunity. The oncolytic vaccinia viruses JX-594-GFP+/hGM-CSF (JX-GFP) and TG6002 are genetically modified by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) or transforming 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU). We compared their properties to kill tumor cells and induce an immunogenic type of cell death in a human melanoma cell model using SK29-MEL melanoma cells. Their influence on human immune cells, specifically regarding the activation of dendritic cells (DCs) and the interaction with the autologous cytotoxic T lymphocyte (CTL) clone, was investigated. Melanoma cells were infected with either JX-GFP or TG6002 alone or in combination with 5-FC and 5-FU. The influence of viral infection on cell viability followed a time- and multiplicity of infection dependent manner. Combination of virus treatment with 5-FU resulted in stronger reduction of cell viability. TG6002 in combination with 5-FC did not significantly strengthen the reduction of cell viability in this setting. Expression of calreticulin and high mobility group 1 protein (HMGB1), markers of immunogenic cell death (ICD), could be detected after viral infection. Accordingly, DC maturation was noted after viral oncolysis. DCs presented stronger expression of activation and maturation markers. The autologous CTL clone IVSB expressed the activation marker CD69, but viral treatment failed to enhance cytotoxicity marker. In summary, vaccinia viruses JX-GFP and TG6002 lyse melanoma cells and induce additional immunostimulatory effects to promote antitumor immune response. Further investigation in vivo is needed to consolidate the data.
Based on our preliminary experiences, patient comfort and safety, parental satisfaction and the rate of complications seem to be promising with this technique.
The closure of the cystic duct using the LVSS is feasible and effective in laparoscopic cholecystectomy in children. However, it is important to keep a safe distance from other intra-abdominal structures when using thermal energy devices to prevent thermal collateral damage.
Because we experienced favourable results with laparoscopic biopsy in our patients, we are of the opinion that laparoscopy-assisted biopsies are well suited for the management of intra-abdominal tumours in systemic malignant disease.
In our opinion, MAG is a feasible, safe procedure in children. Technically, it is a simple method, particularly in cases where percutaneous tube placement is not feasible. It combines the advantages of microlaparoscopy and open surgery. It is easy to perform in children and allows a primary gastrostomy tube placement. Parents and nursing staff also seem satisfied.
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