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.

[The content of the soluble forms PD-1 and PD-L1 in blood serum of patients with gastric cancer and their relationship with clinical and morphological characteristics of the disease.]

Results of comparative ELISA investigation of pretreatment sPD-1 and sPD-L1 content in blood plasma of 100 gastric cancer patients at various disease stages aged 25 to 81 years are presented. Control group included 60 practically healthy donors aged 18 - 68 years. Plasma sPD-L1 concentrations did not differ between gastric cancer patients and control group, and sPD-1 levels were statistically significantly lower in patients than in healthy donors (p<0.0001). Positive correlation (R=0.38; p=0.003) was revealed between plasma sPD-1 и sPD-L1 levels in control group and negative (R= -0.26; p=0,009) - in gastric cancer patients. ROC curve revealed the best sPD-1 cut-off level (< 21 pg/ml) with 77% sensitivity and 63.3% specificity, which is not sufficient for its application as diagnostic marker. Statistically significant increase of plasma sPD-L1 from stage I to stage IIIC (R=0.50; p=0.000011) was found. Analysis of associations between the evaluated markers' levels and indices of gastric cancer expansion according to TNM system revealed statistically significant positive associations of plasma sPD -L1 levels with T (tumor invasiondepth) and N (number of affected lymph nodes) indices: R=0.33; p=0.00093, and R=0.27; p=0.0099 respectively. sPD-L1 level was significantly increased in patients with low differentiated adenocarcinoma and cricoid-cell cancer as compared to highly differentiated adenocarcinoma (p=0.02 and p=0.004 respectively); in patients with cricoid-cell cancer it was also higher than in those with moderately differentiated adenocarcinoma (p=0.043) and undifferentiated cancer (p=0.049). Plasma sPD-1 level did not depend on disease stage, TNM system indices and tumor histological structure. Thus, soluble ligand sPD-L1, but not its receptor sPD-1, plasma level is increased in patients with unfavorable clinical and morphological characteristics, may be regarded as potentially valuable prognostic factor for gastric cancer patients' survival, and probably as a predictor of anti - PD-1/PD-L1 treatment efficiency.

Serum angiogenic factors in patients with neuroendocrine tumors of abdominal organs.

The initial (before treatment) levels of VEGF, endostatin, and tumor necrosis factor-beta (TNF-beta) were measured in the sera of 20 patients with malignant and benign neuroendocrine tumors of the abdominal organs and 25 healthy controls. The initial levels of VEGF, endostatin, and TNF-beta in the total group of patients with neuroendocrine tumors of abdominal organs did not differ from the control. A significant difference was detected between the mean serum concentrations of endostatin in patients with benign and malignant neuroendocrine tumors: 64.1+/-14.7 and 107.8+/-14.1 ng/ml, respectively (p=0.043). The content of VEGF, endostatin, and TNF-beta did not correlate with patients' gender and age. A direct correlation between endostatin, TNF-beta concentrations and maximum size of the primary tumor was detected in patients with malignant neuroendocrine tumors. Direct correlations between the initial levels of VEGF and endostatin and an inverse correlation between VEGF and TNF-beta concentrations were detected in patients with benign neuroendocrine tumors. Relapse-free survival was significantly lower in patients with serum endostatin concentration >100 ng/ml and TNF-beta<30 pg/ml.

Clinical and biochemical aspects of the carcinoid syndrome in neuroendocrine tumors of the abdominal and retroperitoneal organs and its impact for the disease prognosis.

Overall and relapse-free survival of 238 patients with neuroendocrine tumors of the abdominal and retroperitoneal organs was evaluated with consideration for the presence of the carcinoid syndrome. The incidence of the carcinoid syndrome was 15.6%. The presence of the carcinoid syndrome was inessential for survival and relapse prognosis in patients with neuroendocrine tumors of the abdominal and retroperitoneal organs. A trend to the development of earlier relapses was noted in patients with this syndrome. Diarrhea was found to be a prognostically unfavorable factor. The time of the carcinoid syndrome development was prognostically significant in patients with malignant neuroendocrine tumors. The mean secretion of epinephrine, norepinephrine, and dopamine with daily urine was significantly higher in patients with the carcinoid syndrome. A significant positive correlation between urinary excretion of catecholamines was detected (r=0.53; p<0.05).

[Gastric tumor of complex structure].

The paper describes a case of gastric tumor comprising moderately differentiated adenocarcinoma and atypical carcinoid with metastases of both types of tumor cells in the lymph nodes. Electron microscopic and immunohistochemical studies of primary gastric tumor and lymph nodal metastases confirmed the presence of both differentiation types within one space-occupying lesion: such as goblet (mucin-producing) and neuroendocrine cells. The differentiation varied in different fields of vision with a preponderance of low-grade ultrastructural differentiation cells. Thus, electron microscopic and immunohistochemical studies of tumors not only verify their diagnosis and make a histogenetic differential diagnosis of various neoplasms, but also define the degree of their maturation.

Serum interleukin-6 in patients with adrenal tumors.

The mean blood content of interleukin-6 in patients with adrenal tumors was much higher than in healthy donors. No correlations were revealed between interleukin-6 level, patients sex and age, stage and duration of the disease. Interleukin-6 concentration was maximum in patients with adrenocortical cancer. A negative correlation was found between interleukin-6 level and blood cortisol concentration in patients with cortisol-producing adenoma. In patients with aldosterone-producing adenoma, interleukin-6 level tended to correlate negatively with plasma renin activity.