The results of experimental and clinical trials of the agents based on oncolytic Newcastle disease virus (NDV) strains provided hope for the development of virotherapy as a promising method for treating human tumors. However, the mechanism of the antitumor effect of NDV and realization of its cytotoxic potential in a cancer cell remains to be elucidated. In the current work, we have studied the antitumor effect of NDV in a syngeneic model of mouse Krebs-2 carcinoma treated with intratumoral injections of a wild-type strain NDV/Altai/pigeon/770/2011. Virological methods were used for preparation of a virus-containing sample. Colorimetric MTS assay was used to assess the viability of Krebs-2 tumor cells infected with a viral strain in vitro. In vivo virotherapy was performed in eight-week-old male BALB/c mice treated with serial intratumoral injections of NDV in an experimental model of Krebs-2 solid carcinoma. Changes in the tumor nodes of Krebs-2 carcinoma after virotherapy were visualized by MRI and immunohistological staining. Light microscopy examination, immunohistochemical and morphometric analyses have shown that intratumoral viral injections contribute to the inhibition of tumor growth, appearance of necrosis-like changes in the tumor tissue and the antiangiogenic effect of the virus. It has been established that a course of intratumoral virotherapy with NDV/Altai/pigeon/770/2011 strain in a mouse Krebs-2 carcinoma resulted in increased destructive changes in the tumor tissue, in the volume density of necrotic foci and numerical density of endothelial cells expressing CD34 and VEGFR. These results indicate that intratumoral NDV injection reduces tumor progression of an aggressive tumor.

Particular attention in the study of comorbid conditions is paid to viral diseases, in particular, those caused by the pandemic influenza virus type A subtype H1N1, as one of the most pathogenic and contagious. Investigation of the effect of this virus in the development of diabetes mellitus will make it possible to more effectively carry out preclinical studies to find the most effective methods of treating a viral infection against the background of a pre-existing somatic pathology. Purpose of the study was to evaluate the pancreatic toxicity effect of exposure to influenza A/H1N1-California virus in the development of streptozotocin diabetes in DBA/2 and BALB/c mice. Material and methods. Groups of mice DBA/2 (n = 36) and BALB/c (n = 58) were formed: infected with influenza A/H1N1-California virus (at different doses); with the introduction of a solution of streptozotocin at a dose of 150 mg / kg; with the combined use of agents. Life expectancy, blood glucose and insulin level, pathomorphological changes in the pancreas were assessed. Results and discussion. The death of animals was observed only in mice of the DBA/2 line: with the introduction of streptozotocin – 12.5 %, with intranasal infection with the virus (at a dose of 5.7 lg TCID₅₀) – 80 %, with combined exposure – 78 %. A comparative study of mice of the DBA/2 and BALB/c lines showed the possibility of using mice of both lines to study the combined effect of influenza A/H1N1 virus and experimental diabetes, taking into account the dose of infection. Infection of BALB/c mice caused the formation of morphological changes only in the exocrine part of the pancreas. In mice of both lines, after the administration of streptozotocin, persistent hyperglycemia was formed, and pathomorphological changes in the pancreas were recorded mainly in the endocrine part. Similar changes in the pancreas, but more severe, involving the exocrine zone, were found during subsequent infection: in mice of the DBA/2 line in the form of a focal disorder of the acinar structure with degeneration of acinocytes and a compensatory regenerative reaction of cells in intact areas; in mice of the BALB/c line in the form of more significant damage to the ductal system than in DBA/2 with the formation of powerful periductal fibrosis and mononuclear infiltrates. Conclusions. A comparative study showed that DBA/2 mice had more pronounced changes in both the exocrine and endocrine apparatus of the pancreas when infected with influenza A/H1N1-California virus and experimental diabetes mellitus.