Vitamin D serum concentration is not related to the activity of spondyloarthritis - preliminary study.

OBJECTIVE: Vitamin D plays an important role in mineral turnover and bone remodeling and there are increasing data about its immunomodulatory potential in different rheumatologic disorders. Deficiency of vitamin D is frequent in patients with spondyloarthritis (SpA) and some data suggest its association with increased disease activity and structural damage. However, its exact role in the pathogenesis of SpA and its association with disease activity are still a matter of debate. MATERIAL AND METHODS: A cross-sectional study of patients diagnosed with axial spondyloarthritis (axSpA) and peripheral spondyloarthritis (perSpA) according to Assessment of Spondyloarthritis International Society classification criteria was performed. The correlation between concentration of 25-hydroxyvitamin D - 25(OH)D - and disease activity scores (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI, Ankylosing Spondylitis Disease Activity Score - ASDAS), inflammatory markers (C-reactive protein - CRP, erythrocyte sedimentation rate - ESR) and clinical symptoms (arthritis, enthesitis, dactylitis) was performed. RESULTS: We included 40 patients with axSpA and 23 patients with perSpA. The mean concentration of 25(OH)D was 24.9 ng/ml (SD 12.49). Forty-seven (74.6%) patients had 25(OH)D below the recommended threshold (< 30 ng/ml). We found no statistically significant negative correlation between the level of 25(OH)D and disease activity of axSpA and perSpA in terms of clinical symptoms (arthritis, enthesitis, dactylitis), inflammatory markers (ESR, CRP) and disease activity scores (BASDAI, ASDAS). These results did not change after adjustment for supplementation of vitamin D and seasonal variation. CONCLUSIONS: Our data show no correlation between the concentration of 25(OH)D in the serum and disease activity in two subgroups of SpA. However, this does not exclude the potential role of vitamin D in pathogenesis of SpA. Further studies are required to evaluate the optimal range of 25(OH)D serum concentration in axSpA and perSpA patients with its possible immunomodulatory potential and influence on disease activity.

Actual status of therapeutic vaccination in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related death worldwide. Although treatment methods such as surgery, radiotherapy and/or chemotherapy have improved, prognosis remains unsatisfactory, and developing new therapeutic strategies is still an urgent matter. Immunotherapy is a novel therapeutic approach wherein activated immune cells can specifically kill tumour cells. Several lung cancer vaccines have demonstrated prolonged survival time in phase II and III trials, and several clinical trials are under investigation. However, many clinical trials involving cancer vaccination with defined tumour antigens have shown this method to work only in a small number of patients. Cancer immunotherapy is not completely effective in eradicating tumour cells because they evade host immune control.

Modulatory effect of laser irradiation on mastoparan-7-induced contraction.

Mastoparan-7 activates guanine nucleotide-binding proteins (G-proteins) and stimulates both apoptosis and increases in cytoplasmic calcium concentration and may induce smooth muscle contraction. The primary aim of the present study was to evaluate the modulatory effect of laser stimulation on vascular smooth muscle contraction induced by direct stimulation of G-protein with mastoparan-7. Experiments were performed on isolated and perfused tail arteries of Wistar rats. Contraction force in the model was measured by increased levels of perfusion pressure with a constant flow. Irradiation treatment was applied directly to the blood vessels. The laser was applied in increasing doses of 10 mW (E=1.8 J), 30 mW (E=5.5 J) and 110 mW (E=19.8 J). Time of exposure was 3 min for each irradiation. In the laser-stimulated arteries, a significant and dose-dependent decrease was observed. The half maximal effective concentration values were 4.43±2.2x10-8, 2.4±0.56x10-7, 3.2±0.72x10-7 and 7.7±0.3x10-7 M/l in the control and 10, 30 and 110 mW laser irradiation groups, respectively. Significant (P<0.001) changes were identified for all laser treatment groups in comparison with the control. When analyzing the function of calcium ion (Ca2+) stores was analyzed, a significant inhibition of influx from both intra- and extracellular Ca2+ stores was observed. The results from the present study suggested that contraction induced by direct activation of G-protein with mastoparan-7 may by effectively inhibited by laser radiation, and that the effect was associated with an inhibition of Ca2+ influx from both intracellular and extracellular Ca2+ stores.

Real-world Experience of Cabozantinib as Second- or Subsequent Line Treatment in Patients With Metastatic Renal Cell Carcinoma: Data From the Polish Managed Access Program.

BACKGROUND: Cabozantinib is an approved treatment for metastatic renal cell carcinoma (mRCC). This report presents an analysis of the safety profile and efficacy of cabozantinib in an unselected population from Poland. PATIENTS AND METHODS: Patients with mRCC, who had been treated with at least 1 previous agent targeting the vascular endothelial growth factor pathway, were eligible to receive cabozantinib at a once-daily dose of 60 mg orally, according to the Managed Access Program (MAP). Data were collected in 4 Polish centers. Patients who had received ≥ 1 dose of cabozantinib were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. RESULTS: A total of 115 patients were enrolled between October 2016 and March 2018, including 50% with bone metastases, 10% with brain metastases and 4.3% with non-clear-cell RCC; 76% had received ≥ 2 lines of therapy. The median time of follow-up was 12.6 months (95% confidence interval [CI], 11.5-14.1 months). The most common grade 3 and 4 AEs were fatigue (23%), hand-foot syndrome (12%), and diarrhea (10%). Only 4% of patients discontinued treatment owing to AEs, and there were no treatment-related deaths. Partial response was observed in 19% of patients, whereas 56% had stable disease. The median progression-free survival was 12.5 months (95% CI, 9.2-14.2 months), with a 12-month overall survival rate of 70.4% (95% CI, 60.2%-78.5%). CONCLUSIONS: Cabozantinib demonstrated acceptable tolerability and activity in a large unselected population of patients with mRCC under clinical conditions.

Pneumonectomy - permanent injury or still effective method of treatment? Early and long-term results and quality of life after pneumonectomy due to non-small cell lung cancer.

INTRODUCTION: Despite the constant decrease of performed pneumonectomies (PN) in recent years, it is still necessary for 15-20% of patients with non-small cell lung cancer (NSCLC) to undergo total lung resection due to the local progression of the disease. AIM: To assess the frequency and type of postoperative complications, quality of life, and the early and long-term results after PN performed due to NSCLC. MATERIAL AND METHODS: In the total group of 1160 patients, operated on in 2008-2011 due to NSCLC, 192 of them underwent PN (16.6%). The quality of life was analysed using EORTC-QLQ-C30 questionnaire. RESULTS: Perioperative mortality after PN was 4%. Five-year survival reached 45%. The factors that significantly affected the 5-year survival in multivariate analysis were: pTNM stage, pN stage, intrapericardial resection, and additional extrapulmonary structures resection. The mean Global Quality of Life was 50.8. The Symptom Scale ranged from 7 to 54.3, the Functional Scale from 58.2 to 76.3 and the rate for NSCLC symptoms ranged from 2.2 to 48.1. CONCLUSIONS: Pneumonectomies in patients with NSCLC is associated with higher risk of postoperative complications but it does not significantly increase the perioperative mortality. Long-term results in this group of patients are encouraging. According to the questionnaire, the quality of life is favourable. Low intensity of typical NSCLC symptoms was observed. The appropriate qualification for right-sided PN and exclusion of metastasis in N2 nodes are crucial.

Effect of 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzene-sulfonamide on calcium influx in three contraction models.

2,4,6-Trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide (m-3M3FBS) activates phospholipase C and stimulates apoptosis; however, in smooth muscle cells it may increase the perfusion pressure. The main aim of the present study was to evaluate the physiological effect of direct stimulation of phospholipase C on vascular smooth muscle reactivity using three contraction models. Experiments were performed on the isolated and perfused tail artery of Wistar rats. The contraction force in the present model was measured by an increased level of perfusion pressure with a constant flow. Concentration-response curves (CRCs) obtained for phenylephrine, arg-vasopressin, mastoparan-7 and Bay K8644 presented a sigmoidal association. In comparison to the control curves, CRCs in the presence of m-3M3FBS were significantly shifted to the left except for Bay K8644. Analyses of calcium influx suggest that in the presence of m-3M3FBS the calcium influx from intra- and extracellular calcium stores was significantly higher. The results of the present experiments suggest that m-3M3FBS significantly increases the reactivity of vascular smooth muscle stimulated with metabotropic receptors or G-protein by an increase in calcium influx from intra- and extracellular calcium stores. The current knowledge regarding the apoptotic pathway shows the significance of calcium ions involved in this process, thus, m-3M3FBS may induce apoptosis by an increase of cytoplasmic calcium concentration; however, simultaneously, the use of this mechanism in therapy must be preceded by a molecular modification that eliminates a possible vasoconstriction effect.