Aim: To investigate the association of MDM2 expression at the mRNA levels in neuroblastoma with clinical features and unfavorable disease factors to determine the possibility of it usage as a prognostic marker of neuroblastoma. Materials and Methods: Total RNA and DNA were extracted from tumor tissue samples of total 91 neuroblastoma patients (mean age: 39.45 ± 4.81 months). MDM2 mRNA levels were detected with Q-PCR. TP53 gene deletion was detected with FISH method. MYCN amplification was detected with Q -PCR analysis in fresh tumor samples and FISH in FFPE samples. Results: We investigated the association of MDM2 mRNA expression with clinical outcome in neuroblastoma patients (n = 91). Kaplan — Meier curves showed a significant association of high MDM2 expression with poor event-free survival (p < 0.001). Clinical outcome of patients without MYCN amplification with low MDM2 expression was associated with better event-free survival than with high MDM2 expression (p < 0.001). Overexpression of MDM2 can be used as significant prognostic marker for patient stratification on risk groups and treatment optimization. Conclusion: Our results showed that the high expression of MDM2 at mRNA levels is an important factor of neuroblastoma prognosis. It may be a valuable additional molecular marker in guiding specific therapy in MYCN non-amplified NB patients without TP53 gene deletion.

The important component of obesity pathogenesis is inflammatory activation of innate immune cells within adipose tissue and in other body locations. Both the course of obesity and innate immune reactivity are characterized by sex-associated differences. The aim of the work was a comparative investigation of metabolic profiles of phagocytes from different locations in male and female rats with MSG-induced obesity. The administration of monosodium glutamate (MSG) caused obesity, with sex-associated differences, that was more severe in male rats. Obesity was associated with pro-inflammatory activation of CD14+ phagocytes from adipose tissue in female, but not in male rats, which was demonstrated by decreased phagocytosis activity along with increased ROS generation. Phagocytes from the peritoneal cavity and peripheral blood of obese female rats exhibited neutral metabolic profile, whereas those cells from obese male rats displayed a pro-inflammatory metabolic profile. Thus, the manifestation of obesity-induced inflammation was characterized by different patterns of metabolic profile of phagocytes in male and female rats. Identified immune cell characteristics expand our knowledge of obesity immunobiology and may help to develop more effective preventive and therapeutic interventions for obese patients of different sexes.

Aim. MI1 is a promising maleimide derivative, which exhibits antiproliferative effect on different cells. The aim of present study was to investigate influence of MI1 on the cell cycle of cancer cells and its cytotoxity. Methods. The proliferative activity and viability of human cancer cell lines (colorectal adenocarcinoma-Colo-205; breast cancer-MCF-7; cervix cancer HeLa) obtained with MTT-test and cell counts were performed using a tripan blue dye. Distribution of cell cycle phases was obtained using flow cytometry method. Results. In the present study we demonstrate a detectable cytostatic effect of the maleimide derivative MI1 on the epithelial cell lines Colo-205, MCF-7 and HeLa. In the presence of MI1 the number of cells in the G 2 /M+S phases of the cell cycle dropped by 20-30 % (p < 0.05) relative to control. Conclusions. The results suggest that MI1 may be a perspective drug for antitumor therapy and perhaps deserves further study in detail.

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Introduction.Patients with HL normally undergo a risk-adapted treatment based on PET scans. Regardless of HL treatment high efficiency, (80-90% remission), the search of new prognostic markers has been a continued process in recent years. This is related to the disease recurrence in 25-35% of patients in the first 5 years. The studies show that MDSC expands dramatically with tumor growth and causes a tumor immunosuppressed environment. The aim of this study is to investigate the number of MDSC in HL patients' peripheral blood and its correlation with clinical variables when the diagnosis and outcome first set. Methods .43 primary HL patients, (median age: 30, range: 19-78 years; male: 18, female: 25), were included in the study since April, 2018. 58.2% and 41.8% of patients have been diagnosed with early and advanced stages of HL, respectively, and received the ABVD or BEACOPP (14/esc) as a 1st-line treatment regimen. Peripheral blood mononuclear cells (PBMC) were isolated by ficoll density gradient centrifugation treatment, after 2-3 chemotherapy cycles (interim), and at the end of treatment (EOT). We assessed the E-MDSC count (CD33+CD11b+CD14-HLA-DR-) using the anti-human antibodies purchased from Beckman Coulter (Brea, CA, USA). We have also used a routine protocol of metabolic PET assessed according to Deauville criteria of response. Results.83.7% of patients achieved remission (CR/PR) during the follow-up period (median timeline: 18.9 months). We recorded a disease progression in 5 (11.6%) patients during and after the 1st line therapy, (time to relapse - 8 months). In addition, those patients had a high level of MDSC before treatment, which also remained high after interim and EOT-PET. Median of EFS has not been reached and we continue monitoring all patients. The HL patients who achieved remission had an increased E-MDSC percent (median 12.5%) compared to the age and gender control group, (median 2.03%), and the non-responders' one (median 20%). The number of NK-T (CD3+CD16+CD56+) cells increased by 15 % after EOT compared to pretreatment number, 9.2%, p=0.05. PBMC Evaluation at baseline.The E-MSDC count increases significantly with age: 3.1% vs 12.9% in HL patients under 25 years of age vs over 40, respectively p=0.014. Pretreatment MDSC levels were potentially associated with the disease stage: early stages (1A-2A and 2B) vs advanced stages (12% vs 3.9% vs 15%, respectively p=0.07). Our PET imaging tentatively correlated to the above levels. With that, patients with PET 5DS had a higher number of E-MDSC compared to a healthy control group, while the count is reduced in responders during and after treatment (p=0.06). Theoretically, this means that immunosuppression would be reduced and the antitumor immune response of the body would improve. PBMC Evaluation at interim response assessment.At this step, the age was also confirmed as an independent predicting factor in patients under 25 vs &gt; 40, according to the MDSC level (6% vs 11.5%, respectively p=0.008). The level of E-MDSC was higher in patients who failed to achieve CR/PR (p=0.08). PBMC Evaluation at the EOT:90.6% (39/43) and 9.4% (4/43) of patients had a PET-negative and PET-positivestatus at the EOT, respectively (p &lt; 0.05). We found a strong correlation between the EOT-PET and E-MDSC level. With this, patients with EOT-PET-ve had a lower E-MDSC expression vs EOT-PET+ve (12% vs 42% respectively, p=0.0007), which may potentially become a prognostic factor of response prediction. IPS is an important independent prognostic factor positively correlated to the MDSC count at EOT. In our study, patients in the high-risk group (3-4 IPS) had a significantly higher level of MDSC number than the low-risk group (1-2 IPS) and are more likely not to achieve a positive response to treatment (25% vs 18%, respectively p=0.02). Conclusion.The obtained results suggest that the higher level of MDSC number is associated with unfavorable prognosis of HL, reduce response rate. The challenge of strictly prognostic factor application leads to the research of biomarkers in the HL field. The discovery of new prognostic factors will improve an individualized approach to patient treatment and decrease the disease relapse risk. Disclosures No relevant conflicts of interest to declare.