Concurrent thermochemoradiotherapy for brain high-grade glioma

Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas

Predictive and prognostic significance of mRNA expression and DNA copies aberrations of ERCC1, RRM1, TOP1, TOP2A, TUBB3, TYMS, and GSTP1 genes in patients with breast cancer

Increasingly, many researchers are focusing on the sensitivity in breast tumors (BC) to certain chemotherapy drugs and have personalized their research based on the assessment of this sensitivity. One such personalized approach is to assess the chemotherapy’s gene expression, as well as aberrations in the number of DNA copies—deletions and amplifications with the ability to have a significant effect on the gene’s activity. Thus, the aim of this work was to study the predictive and prognostic significance of the expression and chromosomal aberrations of eight chemosensitivity genes in breast cancer patients. Material and methods. The study involved 97 patients with luminal B breast cancer IIB–IIIB stages. DNA and RNA were isolated from samples of tumor tissue before and after treatment. Microarray analysis was performed for all samples on high-density microarrays (DNA chips) of Affymetrix (USA) CytoScanTM HD Array and Clariom™ S Assay, human. Detection of expression level of seven chemosensitivity genes—RRM1, ERCC1, TOP1, TOP2a, TUBB3, TYMS, and GSTP1—was performed using PCR real-time (RT-qPCR). Results. The expression of the RRM1 (AC scheme), TOP2a, TYMS, and TUBB3 genes in patients with an objective response to treatment (complete and partial regression) is higher than in patients with stabilization and progression (p < 0.05). According to our results, the presence of a high level of GSTP1 in a tumor biopsy is associated with the low efficiency of the NAC CP scheme (p = 0.05). The presence of RRM1 deletion is associated with complete and partial regression, as for the TOP1 and TUBB3 genes (p < 0.05). Higher rates of metastatic survival are associated with a high level of expression and amplification of the GSTP1 gene (log-rank test p = 0.02 and p = 0.05). Conclusion. Thus, a complex assessment of the chemotherapy’s gene expression is important not only for understanding the heterogeneity and molecular biology of breast cancer but also to obtain a more accurate disease prognosis

Effect of early-stage human breast carcinoma on monocyte programming

Circulating monocytes are a major source of tumor-associated macrophages (TAMs). TAMs in human breast cancer (BC) support primary tumor growth and metastasis. Neoadjuvant chemotherapy (NAC) is a commonly used treatment for BC patients. The absence of the response to NAC has major negative consequences for the patient: increase of tumor mass, delayed surgery, and unnecessary toxicity. We aimed to identify the effect of BC on the subpopulation content and transcriptome of circulating monocytes. We examined how monocyte phenotypes correlate with the response to NAC. The percentage of CD14-, CD16-, CD163-, and HLA-DR-expressing monocytes was quantified by flow cytometry for patients with T1-4N0-3M0 before NAC. The clinical efficacy of NAC was assessed by RECIST criteria of RECIST 1.1 and by the pathological complete response (pCR). The percentage of CD14+ and СD16+ monocytes did not differ between healthy women and BC patients and did not differ between NAC responders and non-responders. The percentage of CD163-expressing CD14lowCD16+ and CD14+CD16+ monocytes was increased in BC patients compared to healthy women (99.08% vs. 60.00%, p = 0.039, and 98.08% vs. 86.96%, p = 0.046, respectively). Quantitative immunohistology and confocal microscopy demonstrated that increased levels of CD163+ monocytes are recruited in the tumor after NAC. The percentage of CD14lowCD16+ in the total monocyte population positively correlated with the response to NAC assessed by pCR: 8.3% patients with pCR versus 2.5% without pCR (p = 0.018). Search for the specific monocyte surface markers correlating with NAC response evaluated by RECIST 1.1 revealed that patients with no response to NAC had a significantly lower amount of CD14lowCD16+HLA-DR+ cells compared to the patients with clinical response to NAC (55.12% vs. 84.62%, p = 0.005). NGS identified significant changes in the whole transcriptome of monocytes of BC patients. Regulators of inflammation and monocyte migration were upregulated, and genes responsible for the chromatin remodeling were suppressed in monocyte BC patients. In summary, our study demonstrated that presence of BC before distant metastasis is detectable, significantly effects on both monocyte phenotype and transcriptome. The most striking surface markers were CD163 for the presence of BC, and HLA-DR (CD14lowCD16+HLA-DR+) for the response to NAC

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Subfossil Cladocera from a sediment core of small thermokarst Lake in Pechora Delta, Nenets Autonomous Region, northern Russia

Subfossil Cladocera remains were examined from small thermorkarst Lake 17-PE-03 (68.183967 N, 53.808247 E, Pechora Delta, Nenets Autonomous Region, Russia) from one core (48 cm-long). Results of the analysis are presented in date base. For the first time, the species Phreatalona protzi (Hartwig, 1900) (Crustacea: Cladocera) has been found in the Nenets Autonomous Region, Russia

Cladoceran analysis of sediment core 17-Ya-01 from a anonymous lake in the Yamalo-Nenets Autonomous Okrug, Arctic Russia

Cladocerans are very promising for studying climate change risks owing to their inherently predictive nature. For paleoecological study, one sediment core (17-Ya-01) was sampled from lake in Yamalo-Nenets Autonomous Okrug (Russia). Cladoceran analysis of the sediment core with a length of 51 cm collected from the studied lake is performed. A total of 30 taxa were registered in the subfossil cladoceran community of the lake. Most of the identified taxa belong to the Chydoridae family. Bosmina (Eubosmina) longispina was the dominant species. Of special interest is the finding of Ophryoxus gracilis and Rhynchotalona latens - rare species

Palynologycal record of a long sediment core from Lake Shira (Minusinsk Depression, South Siberia, Russia)

In 2022, a 530 cm long sediment core (Shira core 3, 54°31̍18,2̎ N, 90°10̍43,7̎ E) was recovered from 24 m depth in the central part of Lake Shira. Lake Shira is located in Minusinsk Depression of the mountains of Southern Siberia (Khakassia, Russia). It is a meromictic lake with an area of 35.9 km2 and an average depth about 11 m (the maximum depth of 24 m). The lake's salinity varies considerably and can reach up to 27 g/l. The surrounding vegetation consist of steppe associations (Artemisia and Poaceae species predominate), birches and small forest patches

Diatoms from the bottom sediments of Lake Shira (Khakassia, Russia)

Diatoms are good indicators of a variety of lake water conditions including salinity, pH, light availability, temperature and nutrient levels, but diatoms as palaeoindicators are poorly studied in the Lake Shira. Our research on the species composition and ecological parameters of diatoms provide additional data for the regional databases and contributes to improving the accuracy of paleoecological reconstructions. In this study the diatom results of analysis a 528 cm long continuous sediments core from the Lake Shira (Khakassia, Russia) are presented. The core was collected in August 2020 from central part of the lake from a depth of 24 m. 39 samples were investigated by us for diatom analysis. Diatoms were found only in 13 samples. Diatom analysis of samples revealed 30 taxa, belonging to 19 genera. The analysis of the ecological structure of the diatom flora of the sediment core sample from the lake under study shows that it is dominated by the cosmopolitan representatives of benthic and planktonic-benthic, indifferent to salinity and halophiles organisms giving preference to the alkaline environmental conditions. The prevalence of Handmannia comta (Ehrenberg) Kociolek & Khursevich diatom in sediments have been established

Unravelling the Network of Nuclear Matrix Metalloproteinases for Targeted Drug Design

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for the degradation of a wide range of extracellular matrix proteins, which are involved in many cellular processes to ensure the normal development of tissues and organs. Overexpression of MMPs has been observed to facilitate cellular growth, migration, and metastasis of tumor cells during cancer progression. A growing number of these proteins are being found to exist in the nuclei of both healthy and tumor cells, thus highlighting their localization as having a genuine purpose in cellular homeostasis. The mechanism underlying nuclear transport and the effects of MMP nuclear translocation have not yet been fully elucidated. To date, nuclear MMPs appear to have a unique impact on cellular apoptosis and gene regulation, which can have effects on immune response and tumor progression, and thus present themselves as potential therapeutic targets in certain types of cancer or disease. Herein, we highlight and evaluate what progress has been made in this area of research, which clearly has some value as a specific and unique way of targeting the activity of nuclear matrix metalloproteinases within various cell types

New Perspectives on the Role of Nuclear Proteases in Cell Death Pathways

Multiple factors can trigger cell death via various pathways, and nuclear proteases have emerged as essential regulators of these processes. While certain nuclear proteases have been extensively studied and their mechanisms of action are well understood, others remain poorly characterized. Regulation of nuclear protease activity is a promising therapeutic strategy that could selectively induce favorable cell death pathways in specific tissues or organs. Thus, by understanding the roles of newly discovered or predicted nuclear proteases in cell death processes, we can identify new pharmacological targets for improving therapeutic outcomes. In this article, we delved into the role of nuclear proteases in several types of cell death and explore potential avenues for future research and therapeutic development