Additional booster doses in patients with chronic lymphocytic leukemia induce humoral and cellular immune responses to SARS-CoV-2 similar to natural infection regardless ongoing treatments: A study by ERIC, the European Research Initiative on CLL.

Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments.

Correction to: Vitamin D protects endothelial cells from irradiation-induced senescence and apoptosis by modulating MAPK/SirT1 axis.

Unfortunately, the 5th author name has been publisehd incorrectly in the original publication. The complete correct name is given below.

c-Myc Sustains Transformed Phenotype and Promotes Radioresistance of Embryonal Rhabdomyosarcoma Cell Lines.

We have previously reported that the MEK/ERK pathway sustains in vitro and in vivo transformed phenotype and radioresistance of embryonal rhabdomyosarcoma (ERMS) cell lines. Furthermore, we found that aberrant MEK/ERK signaling activation promotes c-Myc oncoprotein accumulation. In this study, the role of c-Myc in sustaining the ERMS transformed and radioresistant phenotype is characterized. RD and TE671 cell lines conditionally expressing MadMyc chimera protein, c-Myc-dominant negative and shRNA directed to c-Myc were used. Targeting c-Myc counteracted in vitro ERMS adherence and in suspension, growth motility and the expression of pro-angiogenic factors. c-Myc depletion decreased MMP-9, MMP-2, u-PA gelatinolytic activity, neural cell adhesion molecule sialylation status, HIF-1α, VEGF and increased TSP-1 protein expression levels. Rapid but not sustained targeting c-Myc radiosensitized ERMS cells by radiation-induced apoptosis, DNA damage and impairing the expression of DNA repair proteins RAD51 and DNA-PKcs, thereby silencing affected ERMS radioresistance. c-Myc sustains ERMS transformed phenotype and radioresistance by protecting cancer cells from radiation-induced apoptosis and DNA damage, while promoting radiation-induced DNA repair. This data suggest that c-Myc targeting can be tested as a promising treatment in cancer therapy.

Vitamin D protects endothelial cells from irradiation-induced senescence and apoptosis by modulating MAPK/SirT1 axis.

PURPOSE: Radiotherapy toxicity is related to oxidative stress-mediated endothelial dysfunction. Here, we investigated on radioprotective properties of Vitamin D (Vit.D) on human endothelial cells (HUVEC). METHODS: HUVEC, pre-treated with Vit.D, were exposed to ionizing radiation (IR): ROS production, cellular viability, apoptosis, senescence and western blot for protein detection were performed. The role of MAPKs pathway was investigated by using U0126 (10 µM) MEKs/ERKs-, SB203580 (2.5 µM) p38-inhibitor or by over/expressing MKK6 p38-upstream activator. RESULTS: Vit.D reduced IR-induced ROS production protecting proliferating and quiescent HUVEC from cellular apoptosis or senescence, respectively, by regulating MAPKs pathways. In proliferating HUVEC, Vit.D prevented IR-induced apoptosis by activating ERKs while in quiescent HUVEC counteracted IR-induced senescence by inhibiting the p38-IR-induced activation. MEKs&ERKs inhibition in proliferating or MKK6/mediated p38 activation in quiescent HUVEC, respectively, reverted anti-apoptotic or anti-senescent Vit.D properties. SirT1 protein expression levels were up-regulated by Vit.D. ERKs inhibition blocked Vit.D-induced SirT1 protein up-regulation in proliferating cells. In quiescent HUVEC cells, p38 inhibition counteracted the IR-induced SirT1 protein down-regulation, while MKK6 transfection abrogated the Vit.D positive effects on SirT1 protein levels after irradiation. SirT1 inhibition by sirtinol blocked the Vit.D radioprotective effects. CONCLUSION: Vit.D protects HUVEC from IR induced/oxidative stress by positively regulating the MAPKs/SirT1 axis.

[Changes in the mineral metabolic indices of osteoarthrosis patients with the use of radon therapy and mud therapy]. / Izmenenie pokazatelei mineral'nogo obmena u bol'nykh osteoartrozom pri ispol'zovanii radonoterapii i griazelecheniia.

As shown by investigations of alkaline phosphatase, plasma levels of calcium, non-organic phosphorus, coefficient Ca/P in 58 patients with osteoarthrosis deformans before and after radon baths, mud applications or their combination, the highest biochemical effect was achieved in a group of patients on mud therapy.

[The nootropic correction of disorders in learning and memory processes induced by extreme exposures]. / Korrektsiia nootropami narushenii protsessov obucheniia i pamiati, vyzvannykh nekotorymi ékstremal'nymi vozdeistviiami.

Experiments on rats demonstrated that the low-intensity electromagnetic field (12.6 cm, 2375 MHz, power density 1 mW/cm2), motion sickness, and electroconvulsive shock provoked the retrograde amnesia in the passive avoidance test. The oxyracetam (100 mg/kg, i.p.), aniracetam (50 mg/kg, i.p.), nooglutil (50 mg/kg, i.p.), meclofenoxate (50 mg/kg, i.p.), pyracetam (200 mg/kg, i.p.), and GABA (200 mg/kg, i.p) prevented the memory-impairing effect of all these extreme factors. On the contrary, the N-acetylglycinamide, semax, and other nootropic drugs were effective only under one or two extreme conditions.

[The clinical significance of the immunological phenotype in non-Hodgkin's lymphomas]. / Klinicheskoe znachenie immunologicheskogo fenotipa nekhodzhskinskikh limfom.

To study immunological phenotype of tumor cells in the blood and tumor tissue of 68 patients with non-Hodgkin's lymphomas, the authors have used flow cytometry of lymphocytes and enzyme immunoassay in cryostat sections of lymph nodes with application of monoclonal antibodies to differentiating antigens of human lymphocytes. Histological types of lymphoma are shown to differ immunophenotypically. Differential antigens of prognostic and diagnostic value have been determined.

[Pathomorphosis of acute leukemia]. / O patomorfoze ostrykh leikozov.

Macro- and microscopic examinations of the viscera and hemopoietic organs of 405 dead patients who had suffered from various forms of acute leukemia were performed as well as microscopic investigations of 560 punch biopsies obtained from 372 patients at different stages of the disease. Pathomorphological findings on acute leukemias are presented, changes in the disease in the course of cytostatic antileukemia treatment are observed. Morphological signs of therapeutic pathomorphosis of acute leukemia involve: reduction or eradication of leukemic growths in the viscera and hemopoietic organs; hemopoietic hypo- and aplasia; dystrophic and necrobiotic alterations in the organs; topographic changes of leukemic proliferates (extramedullary localization of the process); augmentation of infectious and inflammatory complications; other causes of death.

[Characteristics of hematopoiesis in patients with the leukopenic syndrome]. / Kharakteristika krovetvoreniia u bol'nykh s leikopenicheskim sindromom.

The authors present data concerned with a long-term (up to 20 years) prophylactic medical observation over 103 patients with pronounced stable leukopenia. The different pathological processes associated with the development of the leukopenic syndrome were identified as were the reactive shifts in the medullary hemopoiesis of varying intensity. The shifts turned out nonspecific for all the disease entities under study.