Personalized treatment of malignant tumors during pregnancy.

The combination of pregnancy and cancer is a challenge for the patient and a problematic clinical dilemma for the doctor. In this retrospective observational cohort study, we have tried to analyze our experience in the management of such patients. This review includes 41 patients with malignant neoplasms detected during pregnancy who received treatment at the Almazov National Medical Research Centre from 2015-2021. The majority of patients received treatment during pregnancy (n=26, 63.4%): chemotherapy - 19 (46.3%) (in 2 cases in combination with surgery), surgical treatment - 7 (17, 1%) patients. In most cases, delivery was at term (n=28, 68.3%). All children born at term were mature and had no growth restriction, regardless of whether the mothers received treatment during pregnancy or not. When detecting cancer during pregnancy, an immediate follow-up examination is required to assess the extent of the tumor and current fetal state. If pregnancy prolongation is requested, the treatment should not be postponed, except for systemic chemotherapy in the first trimester of pregnancy, pelvic radiation at any term.

Ambroxol increases glucocerebrosidase (GCase) activity and restores GCase translocation in primary patient-derived macrophages in Gaucher disease and Parkinsonism.

Mutations in the glucocerebrosidase gene (GBA) encoding the lysosomal enzyme glucocerebrosidase (GCase) cause Gaucher disease (GD) and are the most commonly known genetic risk factor for Parkinson disease (PD). Ambroxol is one of the most effective pharmacological chaperones of GCase. Fourteen GD patients, six PD patients with mutations in the GBA gene (GBA-PD), and thirty controls were enrolled. GCase activity and hexosylsphingosine (HexSph) concentration were measured in dried blood and macrophage spots using liquid chromatography coupled with tandem mass spectrometry. The effect of ambroxol on GCase translocation to lysosomes was assessed using confocal microscopy. The results showed that ambroxol treatment significantly increased GCase activity in cultured macrophages derived from patient blood monocytic cell (PBMC) of GD (by 3.3-fold) and GBA-PD patients (by 3.5-fold) compared to untreated cells (p < 0.0001 and p < 0.0001, respectively) four days after cultivation. Ambroxol treatment significantly reduced HexSph concentration in GD (by 2.1-fold) and GBA-PD patients (by 1.6-fold) (p < 0.0001 and p < 0.0001, respectively). GD macrophage treatment resulted in increased GCase level and increased enzyme colocalization with the lysosomal marker LAMP2. The possible binding modes of ambroxol to mutant GCase carrying N370S amino acid substitution at pH 4.7 were examined using molecular docking and molecular dynamics simulations. The ambroxol position characterized by minimal binding free energy was observed in close vicinity to the residue, at position 370. Taken together, these data showed that PBMC-derived macrophages could be used for assessing ambroxol therapy response for GD patients and also for GBA-PD patients.

[Benz(a)pyrenes and N-nitrosamines in dry dairy products]. / Izuchenie soderzhaniia benz(a)pyrena i N-nitrozoaminov v sukhikh molochnykh produktakh.

Results of works induding study of effect of different factors (environment, type of equipment, technology) on content of cancerogenic substances in dry milk products were summarized. Possible reasons of appearance of cancerogens in milk in process of drying were determined, dataes of concentration of benz(a)pyren and N-nytrozamens in milk and warmth carrier before and after drying were established. Explanation of separate appearances which connect with change of quantity of cancerogens in product on different stages of drying was suggested.

[Evaluation of a drying procedure for dairy products coming in direct contact with flue gases from the oncologic viewpoint]. / Onkogigienicheskaia otsenka tekhnologii sushki molochnykh produktov pri priamom ikh kontakte s dymovymi gazami.

The study was concerned with ambient air and heat-transfer medium levels of benzo(a)-pyrene (BP) and N-nitrosoamines (NA) measured at the input and output of the drying chamber of two milk dryers using different systems of heat generation. Said concentrations were ascertained in the dried product (casein), too. One installation used electricity-heated ambient air, while the other--air-diluted products of natural gas combustion. No significant difference was registered for both dryers between ambient-air and heat-transfer medium concentrations of BP and two NAs detected--NDMA and NDEA. There was no significant difference between BP levels in the casein produced on those installations, the raw material coming from the same lot. The study registered reverse changes in NDMA and NDEA concentrations, with ambient air being heated in the heat generator and heat-transfer agent cooled in the drying chamber.

[Pulsed method of sampling in monitoring of carcinogenic substances in gaseous atmosphere]. / Pul'satsionnyi sposob otbora prob dlia monitoringa kantserogennykh veshchestv v gazovozdushnoi srede.

Experiments using various types of gas samplers showed that application of A phi A type fibrous material-containing filters for benzo(a)pyrene monitoring may result in significant underestimation of the carcinogen level in the air. The authors developed pulsed sampler using suspended layer of sorbent which proved most effective in catching benzo(a)pyrene in gaseous atmosphere. The unit allows simultaneous sampling of carcinogenic polycyclic aromatic hydrocarbons and N-nitroso compounds.