Демографічні фактори розвитку соціального капіталу

У статті проаналізовано тенденції змін основних демографічних показників в Україні й Донецькому регіоні зокрема, показано вплив цих факторів на розвиток соціального капіталу. Акцентовано, що дослідження демографічних факторів формування соціального капіталу на державному і регіональному рівнях дозволяє відповідним державним органам управління отримувати повну інформацію стосовно будь-яких змін демографічного розвитку та вживати заходів з оптимізації параметрів трудового та інтелектуального потенціалу населення.In the article the tendencies of changes of basic demographic indicators are analysed in Ukraine and Donetsk region in particular, influence of these factors is rotined on development of social capital. It is accented, that research of demographic factors of forming of social capital on state and regional levels allows the proper public organs of management to get complete information on any changes of demographic development and take measures from optimization of parameters of labour and intellectual potential of population

Chemopreventive targeted treatment of head and neck precancer by Wee1 inhibition

HPV-negative head and neck squamous cell carcinomas (HNSCCs) develop in precancerous changes in the mucosal lining of the upper-aerodigestive tract. These precancerous cells contain cancer-associated genomic changes and cause primary tumors and local relapses. Therapeutic strategies to eradicate these precancerous cells are very limited. Using functional genomic screens, we identified the therapeutic vulnerabilities of premalignant mucosal cells, which are shared with fully malignant HNSCC cells. We screened 319 previously identified tumor-lethal siRNAs on a panel of cancer and precancerous cell lines as well as primary fibroblasts. In total we identified 147 tumor-essential genes including 34 druggable candidates. Of these 34, 13 were also essential in premalignant cells. We investigated the variable molecular basis of the vulnerabilities in tumor and premalignant cell lines and found indications of collateral lethality. Wee1-like kinase (WEE1) was amongst the most promising targets for both tumor and precancerous cells. All four precancerous cell lines were highly sensitive to Wee1 inhibition by Adavosertib (AZD1775), while primary keratinocytes tolerated this inhibitor. Wee1 inhibition caused induction of DNA damage during S-phase followed by mitotic failure in (pre)cancer cells. In conclusion, we uncovered Wee1 inhibition as a promising chemopreventive strategy for precancerous cells, with comparable responses as fully transformed HNSCC cells

1053pdgenomics features gf and integration with mri radiomics features rf to develop a prognostic model in oral cavity squamous cell carcinoma oscc

n/

A Prospectively Validated Prognostic Model for Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck Based on Radiomics of Computed Tomography Images

Background: Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) patients have high relapse and mortality rates. Imaging-based decision support may improve out-comes by optimising personalised treatment, and support patient risk stratification. We propose a multifactorial prognostic model including radiomics features to improve risk stratification for advanced HNSCC, compared to TNM eighth edition, the gold standard. Patient and methods: Data of 666 retrospective-and 143 prospective-stage III-IVA/B HNSCC patients were collected. A multivar-iable Cox proportional-hazards model was trained to predict overall survival (OS) using diagnostic CT-based radiomics features extracted from the primary tumour. Separate analyses were performed using TNM8, tumour volume, clinical and biological variables, and combinations thereof with radi-omics features. Patient risk stratification in three groups was assessed through Kaplan–Meier (KM) curves. A log-rank test was performed for significance (p-value < 0.05). The prognostic accuracy was reported through the concordance index (CI). Results: A model combining an 11-feature radiomics signature, clinical and biological variables, TNM8, and volume could significantly stratify the validation cohort into three risk groups (p < 0∙01, CI of 0.79 as validation). Conclusion: A combination of radiomics features with other predictors can predict OS very accurately for advanced HNSCC patients and improves on the current gold standard of TNM8

NK cell-dependent antibody-mediated immunotherapy is improved in vitro and in vivo when combined with agonists for toll-like receptor 2 in head and neck cancer models

The immunosuppressive character of head and neck cancers may explain the relatively low response rates to antibody therapy targeting a tumor antigen, such as cetuximab, and anti-PD-1 checkpoint inhibition. Immunostimulatory agents that overcome tumor-derived inhibitory signals could augment therapeutic efficacy, thereby enhancing tumor elimination and improving patient survival. Here, we demonstrate that cetuximab treatment combined with immunostimulatory agonists for Toll-like receptor (TLR) 2 induces profound immune responses. Natural killer (NK) cells, isolated from healthy individuals or patients with head and neck cancer, harbored enhanced cytotoxic capacity and increased tumor-killing potential in vitro. Additionally, combination treatment increased the release of several pro-inflammatory cytokines and chemokines by NK cells. Tumor-bearing mice that received cetuximab and the TLR2 ligand Pam3CSK4 showed increased infiltration of immune cells into the tumors compared to mice that received cetuximab monotherapy, resulting in a significant delay in tumor growth or even complete tumor regression. Moreover, combination treatment resulted in improved overall survival in vivo. In conclusion, combining tumor-targeting antibody-based immunotherapy with TLR stimulation represents a promising treatment strategy to improve the clinical outcomes of cancer patients. This treatment could well be applied together with other therapeutic strategies such as anti-PD-(L)1 checkpoint inhibition to further overcome immunosuppression.Transplantation and immunomodulatio

Structure of lens proteins: a molecular genetic approach

Contains fulltext : mmubn000001_134399994.pdf (publisher's version ) (Open Access)Promotores : J. Schoenmakers en N. Lubsen127 p