Key Points: B-cell–specific expression of Myd88p.L252P leads to the development of DLBCL in mice. The Myd88p.L252P mutation cooperates with BCL2 amplifications in ABC-DLBCL lymphomagenesis in vivo.

Medical article медицинская статья

Background.Renal cancer is one of the most immunosensitive oncologic diseases. A prominent breakthrough in this field was gained with the development of medications directed to the suppression of PD-1/PD-L immune check-point signaling pathway that in normal physiologic conditions controls autoimmune reactions. Tumor PD-1 and/or PD-L1 expression is investigated both as a predictor of corresponding immunotherapy efficiency, and as molecular markers of overall prognosis and patients’ survival. This goal could be also attained by the measure­ment of soluble forms of these proteins (sPD-1 иsPD-L1) in blood serum.Objective of the study— comparative evaluation ofsPD-1 and sPD-L1 content in blood serum of practically healthy persons and patients with renal cancer and benign kidney tumors; analysis of the associations between these markers and clinical and pathologic characteristics of renal cancer.Materials and methods. 106 renal cancer (64 male and 42 female; age 33—81 years) and 11 patients with benign kidney tumors (3 male and 8 female; age 29—84 years) were included in the study. Control group comprised 19 men and 18 women of matching age. 57patients had stage I, 12 — II, 15 — III and 22 — stage IVrenal cancer. Serum sPD-L1 and sPD-1 concentrations were measured using standard enzyme immunoassay kits (Affimetrix, eBioscience, USA).Results. sPD-L1 levels in blood serum of patients with primary renal cancer and benign tumors were significantly higher than in control (p 0.0001 and p 0.05 respectively). sPD-L1 level significantly increased with disease stage (p 0.001), with T index increase from 1 to 3 declining at T4, was significantly higher in patients with lymph node metastases (both N1, and N2) than in those without such lesions (N0); it was also increased in М+ patients, and in patients with grade III—IVin comparison to grade I—II tumors. sPD-1 levels did not differ sig­nificantly between study groups, did not depend on disease stage, presence of lymph node or distant metastases, but were decreased in patients with Т4 as compared to those with less advanced primary tumor, and were significantly lower in patients with clear-cell than in those with chromophobic or papillary histologic variants.Conclusion. Serum sPD-L1 in renal cancer patients correlates with disease progression and tumor grade, and can be regarded as promising marker for monitoring of anti-PD1/PD-L1 treatment efficiency. Potential clinical implications of sPD-1 require further investigations and analysis.

Gliomas are a heterogeneous group of brain tumors, among which the most aggressive subtype is glioblastoma, accounting for 60% of cases in adults. Available systemic treatment options are few and ineffective, so new approaches to therapies for glioblastoma are in high demand. In total, 131 patients with diffuse glioma were studied. Paired tumor–normal samples were sequenced on the Illumina platform; the panel included 812 genes associated with cancer development. Molecular profiles in clinically distinct groups were investigated. In low-grade glioma (LGG) patients (n = 18), the most common mutations were IDH1/2 (78%), ATRX (33%), TP53 (33%), PIK3CA (17%), and co-deletion 1p/19q (22%). In high-grade glioma (HGG) patients (n = 113), more frequently affected genes were CDKN2A/B (33%), TERTp (71%), PTEN (60%), TP53 (27%), and EGFR (40%). The independent predictors of better prognosis were tumor grade and IDH1/2 mutations. In IDH—wildtype glioblastoma patients, a history of other precedent cancer was associated with worse overall survival (OS), while re-operation and bevacizumab therapy increased OS. Also, among genetic alterations, TERTp mutation and PTEN deletion were markers of poor prognosis. Nine patients received molecular targeted therapy, and the results were evaluated. The search for molecular changes associated with tumor growth and progression is important for diagnosis and choice of therapy.

Background. The most important task in the field of renal-cell cancer (RCC) treatment results improvement is the search and validation of the markers for its early diagnostics still absent in the clinical practice. It was established that even before the onset and/or detection of RCC the level of kidney injury molecule-1 (KIM-1) in blood plasma did increase.Objective of the study — comparative evaluation of KIM-1 levels in blood plasma of practically healthy persons, RCC cancer, benign kidney tumor patients, patients with non-oncological renal pathologies, and analysis of its role in RCC diagnostics and prognosis.Materials and methods. 125 RCC (age 33—81 years), 14 — benign kidney neoplasms (29—84 years) patients, 90patients with chronic nephritis (28—82 years) and 68 practically healthy persons (18—71 years) were included in the study. Plasma KIM-1 content was measured using Human Serum TIM-1/KIM-1/HAVCR Quantikine® ELISA kit (RD Systems Biotechne®, USA).Results. KIM-1 level in blood plasma of RCC and chronic nephritis patients was significantly higher than in control (medians 305, 282 and 37.8pg/ml respectively, p 0.0001). The rate of KIM-1 elevation over cut-offvalue 90pg/ml corresponding to the upper 95 % confidence interval of control in RCC patients comprised 79.2 %, in patients with nephritis — 83 %, in those with benign renal tumors — 50 %. Specificity in relation to healthy control was 96 %. KIM-1 level highly significantly increased with RCC progression, and already at stage I was 4.3-fold higher by median than in control (p 0.0001). Sensitivity of stage I—IIRCC detection at cut-off 90pg/ml comprised 75 %; stage III—IV — 94 %. The highest plasma KIM-1 levels were detected in papillary cancer patients (median 644pg/ml), that was more than 2-fold higher than in clear-cell and 32-fold higher than in chromophobic RCC. Plasma KIM-1 median level was 7-fold higher in patients with G3 4RCC than in those with G12 (p 0.0001). At the cut-off KIM-1 value of 163pg/ml, corresponding to the median at stage I, significant differences in 3.5-years overall survival both in the total group: 49 % at high, 95 % at low marker level (p 0.01), and at stage I RCC: 62 % and 100 % respectively (p 0.05) — were revealed.Conclusion. Plasma KIM-1 may become the first highly sensitive marker for the early detection of RCC, but it does not allow differentiating between oncologic and non-oncologic renal pathologies. Increased basal plasma KIM-1 is an unfavorable prognostic factor irrespective of the stage of tumor progression.

Background: Galectins are a family of β-galactoside binding proteins that regulate the vast majority of cellular functions, including proliferation, migration, adhesion, and phagocytosis in both health and disease. More and more experimental and clinical evidence indicates that galectins are involved in many stages of carcinogenesis, including patients with renal cell carcinoma (RCC). Aim: To analyze the clinical significance of soluble forms of galectins -1, -3, -4, -7, -9 in patients with various histological RCC types. Materials and methods: We performed a retrospective analysis of the clinical significance of galectins -1, -3, -4, -7, -9 in the serum of 140 RCC patients (84 with clear cell RCC (ccRCC), 38 with papillary (papRCC), 18 with chromophobe (chrRCC)) and in 73 healthy donors (control group), who were examined and treated from 2019 to 2023 in the N. N. Blokhin National Medical Research Center of Oncology. Galectin levels were measured in serum (obtained according to standard methods before the initiation of specific treatment) with an enzyme-linked immunosorbent assay. Results: There was a significant increase in serum galectin -1, -3, -9 levels in the whole RCC patient group, compared to the healthy donor control group; no increase was found for galectins -4 and -7. Serum galectin-1 levels in the ccRCC and papRCC patients were significantly higher than those in the controls (p = 0.0003 and p = 0.0135, respectively). No association between the serum galectins -1 and -7 and the clinical and morphological characteristics of RCC was found; however, serum galectin-7 levels in the papRCC patients correlated with the grade of tumor differentiation (r = -0.592; p = 0.001). The area under the ROC curve (AUC) for galectin-1 in ccRCC was 0.721 (p 0.0001), in papRCC 0.673 (p = 0.0086), and in chrRCC 0.576 (p = 0.355). For galectin-7, the ROC AUC values were 0.527 (p = 0.634) in ccRCC, 0.513 (p = 0.845) in papRCC, and 0.566 (p = 0.425) in chrRCC. In all histological types of RCC, there was a significant increase in serum galectin-3 compared to the controls (ccRCC, p = 0.0208; papRCC, p = 0.0014; chrRCC, p = 0.0041). The ROC analysis for galectin-3 in patients with RCC of various histological types showed AUC = 0.721 (p 0.0001) for ccRCC, 0.673 (p = 0.0086) for papRCC, and 0.576 (p = 0.355) for chrRCC. Galectin-9 levels was directly and significantly associated with the tumor size, as well as with regional metastases (r = 0.251, p = 0.021; r = 0.239, p = 0.028, respectively). The AUC values for galectin-4 were 0.619 (p = 0.021) in ccRCC, 0.577 (p = 0.214) in papRCC, and 0.534 (p = 0.666) for chrRCC. For galectin-9, they were 0.649 (p = 0.0075), 0.613 (p = 0.087), and 0.539 (p = 0.637), respectively. Conclusion: The study has demonstrated a certain association between serum galectin -1, -3, -4, -7, and -9 in the patients with RCC of various histological types. Although the results of the ROC analysis indicated average quality of the model, which does not allow for the use of the obtained data for diagnostic purposes, it is necessary to continue the research for better understanding of the mechanisms of galectin functioning, before galectin-based therapeutic agents would be introduced into clinical practice for the treatment of RCC.