Resistance of HNSCC cell models to pan-FGFR inhibition depends on the EMT phenotype associating with clinical outcome.

Background: Focal adhesion signaling involving receptor tyrosine kinases (RTK) and integrins co-controls cancer cell survival and therapy resistance. However, co-dependencies between these receptors and therapeutically exploitable vulnerabilities remain largely elusive in HPV-negative head and neck squamous cell carcinoma (HNSCC).

Methods: The cytotoxic and radiochemosensitizing potential of targeting 10 RTK and β1 integrin was determined in up to 20 3D matrix-grown HNSCC cell models followed by drug screening and patient-derived organoid validation.

β1 integrin mediates unresponsiveness to PI3Kα inhibition for radiochemosensitization of 3D HNSCC models.

Phosphoinositide 3-kinase (PI3K)-α represents a key intracellular signal transducer involved in the regulation of key cell functions such as cell survival and proliferation. Excessive activation of PI3Kα is considered one of the major determinants of cancer therapy resistance. Despite preclinical and clinical evaluation of PI3Kα inhibitors in various tumor entities, including head and neck squamous cell carcinoma (HNSCC), it remains elusive how conventional radiochemotherapy can be enhanced by concurrent PI3K inhibitors and how PI3K deactivation mechanistically exerts its effects.

Targeting integrin α2 as potential strategy for radiochemosensitization of glioblastoma.

Background: Glioblastoma (GBM) is a fast-growing primary brain tumor characterized by high invasiveness and resistance. This results in poor patient survival. Resistance is caused by many factors, including cell-extracellular matrix (ECM) interactions.

Comparison of clinical and echocardiographic parameters of patients with COVID-19 pneumonia three months and one year after discharge.

Aim    To study changes in clinical and echocardiographic parameters in patients after documented COVID-19 pneumonia at 3 months and one year following discharge from the hospital. Material and methods    The study included 116 patients who have had documented COVID-19 pneumonia. Patients underwent a comprehensive clinical evaluation at 3 months ± 2 weeks (visit 1) and at one year ± 3 weeks after discharge from the hospital (visit 2).

Screening and Validation of Molecular Targeted Radiosensitizers.

The development of molecular targeted drugs with radiation and chemotherapy is critically important for improving the outcomes of patients with hard-to-treat, potentially curable cancers. However, too many preclinical studies have not translated into successful radiation oncology trials. Major contributing factors to this insufficiency include poor reproducibility of preclinical data, inadequate preclinical modeling of intertumoral genomic heterogeneity that influences treatment sensitivity in the clinic, and a reliance on tumor growth delay instead of local control (TCD50) endpoints.

Myeloid SOCS3 Deficiency Regulates Angiogenesis via Enhanced Apoptotic Endothelial Cell Engulfment.

Mononuclear phagocytes, such as macrophages and microglia, are key regulators of organ homeostasis including vascularization processes. Here, we investigated the role of the suppressor of cytokine signaling 3 (SOCS3) in myeloid cells as a regulator of mononuclear phagocyte function and their interaction with endothelial cells in the context of sprouting angiogenesis. As compared to SOCS3-sufficient counterparts, SOCS3-deficient microglia and macrophages displayed an increased phagocytic activity toward primary apoptotic endothelial cells, which was associated with an enhanced expression of the opsonin growth arrest-specific 6 (Gas6), a major prophagocytic molecule.

Endothelial-Specific Deficiency of ATG5 (Autophagy Protein 5) Attenuates Ischemia-Related Angiogenesis.

Objective- Pathological angiogenesis, such as exuberant retinal neovascularization during proliferative retinopathies, involves endothelial responses to ischemia/hypoxia and oxidative stress. Autophagy is a clearance system enabling bulk degradation of intracellular components and is implicated in cellular adaptation to stressful conditions. Here, we addressed the role of the ATG5 (autophagy-related protein 5) in endothelial cells in the context of pathological ischemia-related neovascularization in the murine model of retinopathy of prematurity.

Hematopoietic hypoxia-inducible factor 2α deficiency ameliorates pathological retinal neovascularization via modulation of endothelial cell apoptosis.

A hallmark of proliferative retinopathies, such as retinopathy of prematurity (ROP), is a pathological neovascularization orchestrated by hypoxia and the resulting hypoxia-inducible factor (HIF)-dependent response. We studied the role of Hif2α in hematopoietic cells for pathological retina neovascularization in the murine model of ROP, the oxygen-induced retinopathy (OIR) model. Hematopoietic-specific deficiency of Hif2α ameliorated pathological neovascularization in the OIR model, which was accompanied by enhanced endothelial cell apoptosis.

Endogenous developmental endothelial locus-1 limits ischaemia-related angiogenesis by blocking inflammation.

We have recently identified endothelial cell-secreted developmental endothelial locus-1 (Del-1) as an endogenous inhibitor of β2-integrin-dependent leukocyte infiltration. Del-1 was previously also implicated in angiogenesis. Here, we addressed the role of endogenously produced Del-1 in ischaemia-related angiogenesis.

Endothelial-specific deficiency of Junctional Adhesion Molecule-C promotes vessel normalisation in proliferative retinopathy.

In proliferative retinopathies, like proliferative diabetic retinopathy and retinopathy of prematurity (ROP), the hypoxia response is sustained by the failure of the retina to revascularise its ischaemic areas. Non-resolving retina ischaemia/hypoxia results in upregulation of pro-angiogenic factors and pathologic neovascularisation with ectopic, fragile neovessels. Promoting revascularisation of the retinal avascular area could interfere with this vicious cycle and lead to vessel normalisation.

[Characteristics of migration of adipose tissue derived mesenchymal stromal cells after co-cultivation with activated monocytes in vitro].

Mesenchymal stromal cells (MSC) are considered to be promising tool of regenerative medicine. Migration of MSC toward damaged inflammatory site is essential for physiological tissue reparation. Therefore we studied modifications of migratory features of adipose tissue derived MSC (AT-MSC) after co-cultivation with activated monocytes derived from THP-1 cell line.

[Effectiveness of combined systemic and regional chemotherapy in treating patients with metastatic colorectal cancer after extrahepatic progression of the disease].

There was conducted an assessment of the effectiveness of a combination of systemic and regional modes of chemotherapy versus systemic chemoinfusion in treatment of 70 patients with unresectable metastases of colorectal cancer in the liver after extrahepatic progression of a disease. The use of combined therapy statistically significantly increased overall survival more than doubled as compared to a group of systemic chemotherapy (median 10 vs. 4.

[Chemotherapy in patients with non-resectable colorectal cancer metastases to the liver: systemic or regional?].

Efficacy of the-state-of-the-art modalities of systemic and regional chemo-infusion with oxalyplatin (FOLFOX) and irinotecan (FOLFIRI) (162) was compared. Objective response to the former was 40.8%, to the latter--11.