Key Immune Checkpoint PD-1/PD-L1 Signaling Pathway Components in the Blood Serum from Patients with Bone Tumors.

The levels of sPD-1 and sPD-L1 were analyzed in blood serum of 132 patients (age 14-70 years) with primary bone tumors: osteosarcoma (N=39), chondrosarcoma (N=42), Ewing sarcoma (N=9), chordoma (N=12), giant-cell bone tumor (GCBT) (N=16), benign neoplasms (N=14) and in and practically healthy subjects (age 19-58 years; N=27). sPD-L1 levels in all studied bone neoplasms were significantly higher than in the control. Serum sPD-1 level in GCBT patients was significantly higher than in the control, benign neoplasms, chondrosarcoma, and chordoma patients, but did not differ from osteosarcoma group. sPD-1 concentration in Ewing sarcoma was significantly higher than in chordoma and chondrosarcoma, but did not differ from the control. sPD-1 level in chondrosarcoma patients was also lower than in osteosarcoma, Ewing sarcoma, and in the control. Both sPD-1 and sPD-L1 concentrations were not significantly associated with the type of affected bone, process localization, disease stage, tumor histological grade, patients' age and sex. These results suggest the possibility of using these biological markers for preliminary assessment of the character of the process in the bone.

Comparative analysis of the levels of soluble forms of receptor and ligand of the immunity control point PD-1/PD-L1 in the blood serum of patients with typical bone osteosarcoma and chondrosarcoma.

Results of ELISA investigation of the pretreatment sPD-1 and sPD-L1 content in blood serum of 133 bone neoplasms patients aged 6-70 years and 57 practically healthy control persons aged 12-70 years are described. In 14 patients the neoplasms were of a benign character, in 16 - borderline giant-cell bone tumor was diagnosed, and in 103 - malignant bone lesions including 39 osteosarcomas and 42 chondrosarcomas were revealed. The sPD-1 receptor concentrations in blood serum did not differ between control healthy persons and primary bone tumor patients, while serum sPD-L1 level in bone tumor patients was statistically significantly increased (p<0.0000001). By means of ROC curve construction a cut-off sPD-L1 level of 16.5 pg/ml was found that imposed 75,9% sensitivity and 75,4% specificity in relation to healthy control. However, the frequency of sPD-L1 levels exceeding 16.5 pg/ml was approximately similar in benign, borderline and malignant bone tumor patients. Analysis of the pattern of sPD-1 and sPD-L1 circulation in the peripheral blood of patients with the most prevalent malignant bone tumors - osteosarcoma and chondrosarcoma - demonstrated that in both sarcoma types sPD-L1 level was significantly higher than in control, but in patients with chondrogenic tumors the soluble ligand sPD-L1 dominates in the circulation, while in those with osteogenic tumors - sPD-1 receptor prevails. In particular, sPD-1 level is statistically significantly higher in patients with typical osteosarcoma than in those with typical chondrosarcoma (p=0.002437), and sPD-L1/sPD-1 concentration ratio in chondrosarcoma is highly significantly more than 2-fold higher than in osteosarcoma (0.81 and 0.35 respectively; p=0.000284). The sensitivity of sPD-L1 ≥16.5 pg/ml test in typical osteosarcoma patients' group comprised only 70.2%, and in those with typical chondrosarcoma - 84.6%. Serum sPD-1 and sPD-L1 concentrations in osteosarcoma and chondrosarcoma patients were not associated with the indices of tumor advancement, its histological grade, localization in the osseous system, and type of affected bone. Thus, it can be concluded that the ratio between circulating soluble forms of the receptor and the ligand of PD-1/PD-L signaling pathway differs between patients with chondrogenic and those with osteogenic tumors, sPD-L1 being diagnostically valuable mostly for chondrogenic bone neoplasms.

[Surgical treatment of malignant tumors of the thoracic wall].

23 patients with malignant tumors of the thoracic wall, invading bone structures, were operated in the period of 2005-2009 years. Thoracic wall reconstruction was performed in 20 (77%) of patients. The type of the reconstruction was defined by tumor localization, volume of resection, anatomic features of transplantational tissue flaps. Surgical method remains the mainstay in the treatment of the thoracic wall tumors. Although in cases of highly malignant bone or soft tissue sarcomas, only combined and complex methods allow the achievement of satisfactory results.

The fractal skeleton of the atomic structure of amorphous metals.

The atomic structure of pure amorphous Re and Re-Tb amorphous alloys was studied by the molecular dynamics method. Analysis of the atomic structure of amorphous metals was performed within the framework of percolation theory and fractal geometry. The structure of amorphous metals consists of dense and sparse areas. We established that the dense areas form the fractal skeleton of an amorphous material. The distribution of clusters by size, the probability of an atom belonging to the largest cluster, the fractal dimensionality of the percolation cluster and the concentration dependence of the percolation radius were calculated. Correlation between some physical properties of amorphous metals and their cluster structure was established.

[Comparative evaluation of effects of various bronchodilators in sarcoidosis]. / Sravnitel'naia otsenka deistviia razlichnykh bronkholitikov pri sarkoidoze.

The investigation was undertaken to compare three bronchodilators on patients with respiratory sarcoidosis. Ninety patients (66 females and 24 males) with intrathoracic sarcoidosis were examined. X-ray stages I, II, III, and IV were seen in 48.9, 46.7, 3.3, and 1.1%, respectively. A flow-volume curve was recorded on a Masterscreen Pnevmo apparatus (Erich Jaeger) before and after inhalations of salbutamol (200 micrograms, a flask), ipratropium bromide (40 micrograms, a flask), and 1 ml of berodual solution through a Boreal nebulizer. The mean baseline values of forced expiration were normal, except for MOS75 (51.0 +/- 1.3% of the normal values). After salbutamol, the increment of MOS75 was higher than that after ipratropium (20.7 +/- 3.1% and 12.3 +/- 2.3%, respectively, p < 0.05); however, after berodual nebulization, the increase in MOS50 was greater than that after inhalation of ipratropium (17.2 +/- 1.9% versus 10.7 +/- 1.6%, p < 0.05) or salbutamol (10.1 +/- 6%, p < 0.01). The changes in these parameters in smokers and nonsmokers were similar. The one-month or more inhalation of budesonide (benacort) potentiated the bronchodilating action of salbutamol on all the parameters of forced expiration, but failed to affect the effect of ipratropium and berodual. Prednisolone did not affect the effects of bronchodilators. A combination of beta 2 agonist and inhaled steroid may be effective in intrathoracic sarcoidosis with the bronchial obstruction syndrome. The mechanism of varying action of the drugs having different mechanisms of action requires further investigations.