[Indicators of kidney damage in patients with multiple myeloma in the process of chemotherapeutic treatment.]

The purpose was to study the level of acute kidney injury markers cystatin C, KIM-1, IL-18, NGAL and L-FABR in the blood and urine of patients with the initially identified secreting multiple myeloma (MM) before and during chemotherapeutic treatment. The content of renal markers was examined by ELISA using commercial kits. The study included 23 patients with MM who received 6-8 21-day cycles of chemotherapy (CT) according to the VCD scheme. The results were compared in the main group of 13 patients who had a selective plasma exchange a day before each of the cycles of HT with the use of the Evaclio plasma separator and in a control group of 10 patients treated without extracorporeal detoxification. MM patients before treatment showed an increase in blood IL-18 level of 8.6 times, KIM-1 - 3.1 times, L-FABR - 57.4%, cystatin C - 48.4% and also a decrease in the level of NGAL in 75% of patients by 74.3% compared to the level in healthy, while in the urine initially increased only KIM-1 content by 2.4 times and NGAL by 2.6 times. Conducting multi-course chemotherapy with previous plasma exchange had a more lenient effect on MM patients, as evidenced by a lower KIM-1 level in blood and urine after 1 and 2 courses of HT, as well as IL-18 in blood and urine after 1 course of HT in patients of primary group compared with the control group. For patients with a fatal outcome, a sharp increase in the levels of cystatin C, NGAL and L-FABR is characteristic. The analysis of the dynamics of the studied markers of renal damage indicates the correlation of their level with the clinical features of individual patients, the success and tolerability of chemotherapeutic treatment of MM.

[A plasminogen regulation system in brain tumors]. / Sistema reguliatsii plazminogena v razlichnykh opukholiakh golovnogo mozga.

INTRODUCTION: Tumor progression and neovascularization during malignant processes are believed to be associated with plasminogen activators and the PAI-1 inhibitor, but their role and interactions in various types of brain tumors have been studied insufficiently. AIM: To conduct a comparative study of plasminogen regulation in optic nerve sheath meningiomas, glioblastomas, and brain metastases of breast cancer, as well as in perifocal tissues surrounding the tumors. MATERIAL AND METHODS: Tumors and perifocal areas of 19 breast cancer (BC) metastases, 24 glioblastomas, and 13 meningiomas without perifocal edema were investigated by ELISA in 56 patients aged 35-72 years. Histological control was carried out in each case. RESULTS: Significant differences were found in the levels of urokinase (uPA), tissue plasminogen activator (tPA), and PAI-1 inhibitor between glioblastomas and breast cancer metastases and the histologically unaltered (relatively intact) tissue around meningioma lesions (p≤0.05 in all cases). The levels of uPA-AG and uPA-act in meningioma were higher than those in the relatively intact tissue, while the levels of both tPA forms were reduced. The levels of uPA-AG and uPA-act in both malignant tumors and their perifocal areas were elevated compared to those in the relatively intact tissue. The levels of both tPA forms were reduced in all other tissues, except for glioblastoma. The level of PAI-1 inhibitor in malignant tissues was higher (being predominant in tumors) compared to that in the intact tissue surrounding meningioma, as well as relative to that in meningioma. The study proves that uPA and its inhibitor PAI-1 are directly involved in the metabolism of malignant gliomas and brain metastases of breast cancer. The role of tPA is to protect meningiomas; tPA activation in malignant brain tumors is suppressed.

Sex-Related Characteristics of Systemic Hormonal Homeostasis in Rats with Sarcoma C-45 Cells Transplanted to the Lung.

Sex-related systemic status of pituitary and thyroid hormones and cortisol was studied in rats on days 7 and 14 after transplantation of sarcoma C-45 cells into the lung. Females demonstrated slower development of the tumor process (49.0±10.7 vs. 32.0±3.9 days in males). Injection of tumor cells causes similar disorders in the levels of ACTH, thyrotropic hormone, and prolactin in males and females and opposite disorders in the thyroid and glucocorticoid homeostasis associated in males (in contrast to females) with reduction of cortisol level (by 1.9 times) and increase in the concentrations of total thyroxine forms (by 1.4 times) and triiodothyronine (by 2.9 times) by day 14. Early sex-related shifts in the status of hormone that are a component of the adaptive system attest to their possible relationship with different course of the malignant process in male and female rats.

[[Gender Differences in Tissue Cascade of Activation of Plasminogen and PAI-1 in Esophageal Squamous Cell Carcinoma].]

AIM: comparative analysis of uPA-Ag, uPA-act, tPA-Ag, tPA-act, PAl--Ag and PAl-i-act in tissues of esophageal squamous cell carcinoma (ESCC) in men (M) and women (W) to clarify some pathogenesis issues. MATERIAL AND METHODS: Tumor tissue of ESCC and its perifocal area (19 M and 8 menopausal W aged 38-72 years, st 1I, G2, T,3N M0) were studied by ELISA using standard test kits. RESULTS: ESCC tissue of M showed an increase in both uPA types from the resection line (RL), while in W only uPA-act was increased. tPA-Ag was decreased in tumors of W, tPA-act - in tumors of all patients. Levels of both PAl-- types were higher in ESCC of M than in W. in M, tPA-Ag in perifocal area was lower than in RL, while in W, on the contrary, it was higher. tPA- Ag/tPA-act coefficient in M tumors was 5.7 times higher than in W; in perifocal area it was reduced in all patients, being at the same time in M lower than in W. Both PAl- types were increased in malignant tissues of all patients, prevailing in M tumors, and PAl-i-Ag in peritumoral tissue was higher in M than in W. CONCLUSIONS: Significant gender differences were found in expression of uPA, tPA and PAl-i in tissues of esophageal squamous cell carcinoma. Presence of tumor-associated uPA, PAH and tPA in men and uPA and PAl-i in women is possible in tumor tissue of esophageal squamous cell carcinoma and its perifocal area. Determination of plasminogen regulation system in tissues of esophageal squamous cell carcinoma can be used for the selection and individualization of postoperative treatments.

CHARACTERISTICS OF THYROID STATUS IN EXPERIMENTAL LIVER METASTASIS.

Aim of the study was to analyze the dynamics of thyroid hormones in the pituitary gland, thyroid gland (TG) and blood serum (BS) in liver metastases to reveal thyroid profile of metastasis and to find thyroid markers-of metastasis in BS. MATERIAL AND METHODS: The experiment included 44 white male rats weighing 180-250 g. Sarcoma 45 (S-45) was transplanted intrasplenically after the spleen was brought under the skin. Levels of thyroid hormones: thyroid stimulating hormone (TSH) in the pituitary gland, TG, BS; free (FT4) and total (T4) thyroxine and free (FT3) and total (T3) triiodothyronine in TG and BS were studied by radioimmunoassay (Immunotech, Czech Republic; Arian analyzer, Russia). RESULTS: From the first days of the tumor development, pituitary gland strain with TSH hyperproduction was observed, and later TG hypofunctioning developed. Quantitative changes of thyroid hormones in organs did not correspond to their dynamics in BS. First diagnostic signs of experimental liver metastases, under the absence of formed metastases in the organ, were hyper-TSH-emy and the tendency to FT3 decreasing in BS. Typical characteristics of the "climax" of liver metastasis included formation of a marked "low TB" syndrome which transformed into a more severe "lowT3/lowT4" syndrome in secondary metastasis to the lungs. CONCLUSIONS: Thus, primary tumor growth and development of metastases are accompanied by the strain and imbalanced functioning of the thyroid system. Analysis of dynamics of the thyroid axis hormones in BS allows prognosis of liver metastases, as well as contributes to identifying the point of no return for the disease development which leads to secondary metastasis and irreversible progression of the process.

[Indicators of plasminogen activation system and growth factors in the tissue of nevi and skin melanoma].

Skin melanoma is believed to result from malignization of an inborn or acquired pigmented nevus under the action of a number of causative agents. With regard to this, the comparative analysis of skin melanoma tissue samples taken from patients of both sexes and pigmented nevus tissue samples was performed by polarization fluoroimmunoassay. The study involved analyzing the activity of plasmin, plasminogen, concentration and activity of urokinase type plasminogen activator, tissue type plasminogen activator, plasminogen activator inhibitor, as well as the level of growth factors--vasculoendothelial one and its receptor, epidermal one and its receptor, transforming one, fibroblasts growth factor, insulin-like 1 and 2 growth factors. The detected changes indicate possible mechanisms of malignant transformation of skin nevi. The obtained results can be used for developing the risk evaluation methods for neoplastic transformation of nevi as well as prevention methods.