Relationship between plasma cell-free DNA changes and lysyl oxidase during the treatment and prognosis of canine transmissible venereal tumors.

BACKGROUND: Transmissible venereal tumors (TVT) are a wide range of canine tumors for which there are no effective markers to monitor the therapeutic response in real-time. Circulating biomarkers can be valuable in early cancer diagnosis and prognosis. Accordingly, this study aimed to investigate the significance of the cell-free DNA (cfDNA) and cfDNA integrity index to monitor the response of TVTs to vincristine and compare them with lysyl oxidase activity. Plasma and sera were collected from fifteen male dogs within four weeks before drug administration. The analytical method was mainly based on the quantitative polymerase chain reaction (qPCR) technique for short and long cfDNAs and lysyl oxidase activity was measured in serum. RESULTS: The results of the cfDNA integrity index showed a significant (p < 0.05) difference in the baseline concentration compared to the second and third weeks (with cut-off values of 1.118 and 93.33% specificity). The cfDNA integrity index increased over time due to the reduction of short cfDNAs in the first week after treatment. Lysyl oxidase activity increased during the fourth week (p < 0.001), but there were no significant differences in the other weeks compared to the baseline. The ROC analysis of lysyl oxidase revealed high sensitivity (100%) and specificity (90%) on the second and third weeks compared to the baseline. Multivariate analysis between cfDNA integrity index and lysyl oxidase showed significant correlation (p < 0.05) only in baseline results. CONCLUSIONS: Overall, short cfDNA, the cfDNA integrity index, and lysyl oxidase activity can be proposed as diagnostic biomarkers and putative prognostic candidates in TVT patients. These biomarkers can be combined with cytology to quickly diagnose TVT.

Human placenta-derived mesenchymal stem cells transplantation in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 (phase I clinical trial): safety profile assessment.

BACKGROUND: High morbidity and mortality rates of the COVID-19 pandemic have made it a global health priority. Acute respiratory distress syndrome (ARDS) is one of the most important causes of death in COVID-19 patients. Mesenchymal stem cells have been the subject of many clinical trials for the treatment of ARDS because of their immunomodulatory, anti-inflammatory, and regenerative potentials. The aim of this phase I clinical trial was the safety assessment of allogeneic placenta-derived mesenchymal stem cells (PL-MSCs) intravenous injection in patients with ARDS induced by COVID-19. METHODS: We enrolled 20 patients suffering from ARDS caused by COVID-19 who had been admitted to the intensive care unit. PL-MSCs were isolated and propagated using a xeno-free/GMP compliant protocol. Each patient in the treatment group (N = 10) received standard treatment and a single dose of 1 × 106 cells/kg PL-MSCs intravenously. The control groups (N = 10) only received the standard treatment. Clinical signs and laboratory tests were evaluated in all participants at the baseline and during 28 days follow-ups. RESULTS: No adverse events were observed in the PL-MSC group. Mean length of hospitalization, serum oxygen saturation, and other clinical and laboratory parameters were not significantly different in the two groups (p > 0.05). CONCLUSION: Our results demonstrated that intravenous administration of PL-MSCs in patients with COVID-19 related ARDS is safe and feasible. Further studies whit higher cell doses and repeated injections are needed to evaluate the efficacy of this treatment modality. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); IRCT20200621047859N4. Registered 1 March 2021, https://en.irct.ir/trial/52947 .