Accurate prediction of the outcome of molecular target-based treatment in advanced renal cell carcinoma (RCC) is an important clinical problem. Positron emission tomography/computed tomography using [18F]-2-fluoro-2-deoxyglucose (FDG PET/CT) is a noninvasive tool for the assessment of glucose accumulation which can be a marker of the biological characteristics of the tumor. In this paper, we assess FDG PET/CT as a survival prognostic marker in patients with advanced RCC. The study included 121 patients treated in the years 2011–2016 with a diagnosis of advanced renal cell carcinoma (stage IV, multifocal metastases in all patients). Assessment using FDG PET/CT was conducted by measuring the maximum standard uptake value (SUVmax) for the marker used (the highest SUV measurement result for each patient in a single examination). SUVmax measurements were compared with various clinical risk factors used as prognostic markers. The median follow-up period was 19 months (ranging from 3 to 61 months). SUVmax measurements in all patients ranged from 1.3 to 30.0 (median 6.9). Higher SUVmax was correlated with poorer prognosis. Multi-way analysis with standard risk factors revealed that SUVmax was an independent factor for overall survival (OS; p < 0.003, hazard ratio 1.312, 95% CI 1.147–1.346). For SUVmax < 7.0, median OS was 32 months. For 7.0 ≤ SUVmax < 12.0, median OS was 12.5 months. For SUVmax ≥ 12.0, median OS was 10 months. The differences were statistically significant. A preliminary SUVmax assessment conducted using FDG PET/CT can provide information useful in the prediction of survival of patients with advanced RCC.

Previous studies have suggested that hepatocyte growth factor (HGF) inhibits lung fibrosis as an antagonist of transforming growth factor β (TGF‑β). We assessed HGF expression levels in the lower airways of patients with selected interstitial lung diseases. HGF levels were examined by an enzyme‑linked immunosorbent assay in bronchoalveolar lavage (BAL) fluid supernatants from patients with pulmonary sarcoidosis (PS, n = 52), idiopathic pulmonary fibrosis (IPF, n = 23), nonspecific interstitial pneumonia (NSIP, n = 14), extrinsic allergic alveolitis (EAA, n = 6), bronchiolitis obliterans organizing pneumonia (BOOP, n = 8), chronic eosinophilic pneumonia (EP, n = 6), and in control subjects (n = 13). Intracellular HGF expression in BAL cells was evaluated by flow cytometry. HGF concentrations were elevated in BAL fluid from nonsmokers with IPF (261 ±204 pg/ml, P <0.02), smokers with IPF (220 ±13 pg/ml, P <0.001), and smokers with PS (172 ±33 pg/ml, P <0.02), as compared with controls (148 ±17 pg/ml for nonsmokers; 137 ±9 pg/ml for smokers). HGF levels were positively correlated with TGF‑β concentrations in BAL fluid (r = 0.3; P = 0.02) and negatively-with vital capacity (r = -0.2; P = 0.02). BAL neutrophils, and, for the first time, BAL lymphocytes, were identified as intracellular HGF‑positive cells. Our results do not support evidence for strong antifibrotic HGF activity. The highest HGF concentrations were observed in BAL fluid from patients with IPF, and they were also positively correlated with TGF‑β levels. Thus, although the local protective mechanisms such as the HGF expression are upregulated in chronic interstitial lung diseases, they are not enough to prevent lung fibrosis.

INTRODUCTION Interleukin 27 (IL-27) is a cytokine secreted mostly by antigen-presenting cells. It is important for the immune polarization of T helper-1 (Th1) cells, and its role in interstitial lung diseases (ILDs) and lung cancer has been investigated. Objectives We assessed IL-27 expression in the lower airways of patients with selected ILDs and early-stage non-small cell lung cancer (NSCLC). Patients and methods IL-27 concentrations were examined by an enzyme-linked immunosorbent assay in bronchoalveolar lavage (BAL) fluid supernatants collected from patients with pulmonary sarcoidosis (PS; n = 30), extrinsic allergic alveolitis (EAA; n = 14), idiopathic pulmonary fibrosis (IPF; n = 12), nonspecific interstitial pneumonia (NSIP; n = 14), and NSCLC stages I to IIa (n = 16) with peripheral localization, and in controls (n = 14). The major lymphocyte subsets in BAL fluid were phenotyped, and intracellular IL-27 expression was evaluated by flow cytometry. Results IL-27 concentrations in BAL fluid supernatants were significantly increased in Th1-mediated conditions such as EAA and PS, but not in IPF or NSIP. The highest IL-27 levels (median [SEM], 16.9 [17.5] pg/ml) were reported for NCSLC, and the lowest-for controls (median [SEM], 0.4 [0.2] pg/ml). IL-27 was undetectable in corticosteroid-treated patients with PS. Both CD4(+) and CD8(+) lymphocytes were positive for IL-27; they were a possible local source of IL-27 because the cytokine levels were positively significantly correlated with the total number of lymphocytes, including CD4(+) cells. Conclusions Our results support the Th1-linked activity of IL-27 in ILDs. Early-stage NSCLC is characterized by high IL-27 expression in the lower airways. IL-27 is produced by a high percentage of CD4(+) and CD8(+) cells in BAL fluid, both in patients and controls.

Background: Chronic lymphocytic leukemia (CLL) is characterized by malignant B lymphocyte accumulation and progressive immune dysfunction. The immune checkpoint molecule TIM-3 and its ligand galectin-9 (Gal-9) contribute to T cell exhaustion, impairing anti-tumour immunity. Interleukin-27 (IL-27) has pleiotropic immunomodulatory properties, but its impact on TIM-3 and Gal-9 expression in CLL remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from 20 treatment-naive CLL patients were cultured with or without IL-27 (100 ng/mL) for 72 h. Flow cytometry assessed TIM-3 and Gal-9 expression on CD4⁺, CD8⁺, and CD19⁺ cells. Results: IL-27 stimulation significantly increased TIM-3 expression on CD8⁺ T cells (2.18 ± 0.32% vs. 3.09 ± 0.49%, p = 0.009), a hallmark of T cell exhaustion. IL-27 also modestly increased intracellular Gal-9 levels in total lymphocytes (93.91 ± 1.17% vs. 96.55 ± 0.67%, p = 0.005). Additionally, IL-27 reduced CD4⁺ T cell proportions (26.71 ± 4.19% vs. 22.01 ± 3.23%, p = 0.010). Although numerically modest, these changes may be biologically pertinent in the context of checkpoint-mediated CD8⁺ T-cell exhaustion. Conclusions: IL-27 may enhance immunosuppressive mechanisms in CLL by modulating immune checkpoint expression, potentially contributing to disease progression. These ex vivo findings in PBMCs from CLL patients indicate the IL-27-associated modulation of checkpoint expression under the conditions tested. In the absence of parallel healthy-donor controls, CLL specificity cannot be established in this study.

Recent studies indicate a protective role of vitamin D supplementation against sports performance-induced dysregulation of body homeostasis. However, the effects of a single high dose of vitamin D on changes in bone formation and resorption markers due to ultramarathon running have yet to be explored. This study aimed to analyze the effect of a single high-dose vitamin D supplementation on serum levels of bone turnover markers after a mountain ultramarathon run. In this clinical trial (reg. number NCT03417700), 35 semiprofessional male ultramarathon runners were assigned into two groups: supplemented group, administered a single high dose of vitamin D₃ (cholecalciferol, 150,000 IU) in vegetable oil 24 h before the start of the run (n = 16), and placebo group (n = 19), administered placebo solution 24 h before the start of the run. Blood samples were collected for analysis at three timepoints: 24 h before, immediately after, and 24 h after the run. Serum 25(OH)D₃ level significantly increased (p ≤ 0.05.) after the ultramarathon in both groups. The increase was more pronounced in the supplemented population, especially 24 h after the run (147.01% vs 84.71%). According to post-hoc and other analyses, the levels of N-terminal propeptides of type I collagen, a PINP marker, were increased immediately after the run. The increase was significantly higher in the supplemented group than in the control group. CTX, PTH, sclerostin, and procalcitonin levels were significantly higher 24 h after the run in the control group. The observed attenuation of post-exercise bone resorption and enhancement of bone formation suggest that vitamin D supplementation may modulate bone metabolism in response to extreme physical exertion, potentially through effects on calcium - PTH homeostasis.