41 research outputs found
ROLE OF TARGETED THERAPY IN THE COMBINATION TREATMENT OF PATIENTS WITH KIDNEY CANCER AND METASTATIC BRAIN INVOLVEMENT
In patients with kidney cancer (KC), the rate of metastatic brain involvement is 2-11%, is steadily growing, and is one of the important reasons for treatment failures in these patients. Surgery and radiotherapy, including radiosurgery, must be considered as optimal treatments for patients with KC and brain metastases. Systemic drug therapy has recently played a more and more increasing role in the treatment of patients with a progressive brain tumor process. At the same time, there are no exact pharmacokinetic data on drugs registered for the treatment of disseminated KC in respect to their concentration in the human central nervous when they are used in therapeutic doses. On the basis of the data of the literature review and the results of the authorsβ studies, it may be concluded that while none of the target agents has still shown any significant advantage over others in treating KC patients with brain metastases. All the drugs have demonstrated their ability to achieve a clinical and X-ray verified objective effect (as stabilizations in most cases) in treating brain metastases. The most data are available on the therapeutic efficacy of sunitinib and sorafenib. In case of progressive brain tumor process, drug treatment should be individually discussed in each situation in accordance with standard approaches to treating patients with disseminated KC
COMBINED CHEMOTHERAPY INCLUDING PROCARBAZINE (NATULAN) IN THE TREATMENT OF ANAPLASTIC OLIGODENDROGLIOMAS
Our investigation has demonstrated the high efficiency of combined chemotherapy (CT) including procarbazine + lomustine or procarbazine + lomustine + vincristine in patients with anaplastic oligodendrogliomas. Postoperative CT has been recently recommended for patients with deletion of chromosomes 1p and 19q, by taking into account the good prognosis of a therapeutic effect, better parameters of time till progression in this patient group, and a risk for cognitive impairments after brain radiotherapy
Π‘RANIAL AND INTRACRANIAL METASTASES OF THYROID CANCER
Thyroid cancer metastasis to the brain is rare and little-studied pathology. Problems of their diagnosis and treatment remain to be solved. Features of this group is a metastatic lesion of the brain and bones of the cranial vault with extra- and intracranial growth. The paper details the clinical picture, X-ray, morphological diagnosis and treatment of patients with intracranial metastases thyroid cancer
Π₯ΠΠ Π£Π ΠΠΠ§ΠΠ‘ΠΠΠ ΠΠ’ΠΠ Π ΠΠΠΠΠΠΠΠ‘ΠΠΠ ΠΠΠ§ΠΠΠΠ ΠΠΠ¦ΠΠΠΠ’ΠΠ Π‘ Π¦ΠΠ ΠΠΠ ΠΠΠ¬ΠΠ«ΠΠ ΠΠΠ’ΠΠ‘Π’ΠΠΠΠΠ Π ΠΠΠ ΠΠΠΠΠ§ΠΠΠ ΠΠΠΠΠΠ«
Brain metastases of breast cancer are severe complication of oncological process. Despite the spreading of the process, many patients receive treatment and live for years in contrast to patients with cerebral metastases of other cancers (lung cancer, melanoma, renal cell carcinoma). At different stages of metastatic disease in these patients may be offered different types of treatment: chemotherapy, hormonal therapy, targeted therapy, radiotherapy, radiosurgery, surgical treatment. However, there are no standards that define the indications for surgical treatment of cerebral metastases of breast cancer. This article describes the surgical techniques and defines indications and contraindications for surgical treatment.Π¦Π΅ΡΠ΅Π±ΡΠ°Π»ΡΠ½ΡΠ΅ ΠΌΠ΅ΡΠ°ΡΡΠ°Π·Ρ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΡΠ²Π»ΡΡΡΡΡ Π³ΡΠΎΠ·Π½ΡΠΌ ΠΎΡΠ»ΠΎΠΆΠ½Π΅Π½ΠΈΠ΅ΠΌ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΡΠ΅ΡΡΠ°. ΠΠ΅ΡΠΌΠΎΡΡΡ Π½Π° Π΄ΠΈΡΡΠ΅ΠΌΠΈΠ½Π°ΡΠΈΡ ΠΏΡΠΎΡΠ΅ΡΡΠ° ΠΌΠ½ΠΎΠ³ΠΈΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΊΠΈ ΠΆΠΈΠ²ΡΡ ΠΈ ΠΏΠΎΠ»ΡΡΠ°ΡΡ Π»Π΅ΡΠ΅Π½ΠΈΠ΅ Π³ΠΎΠ΄Π°ΠΌΠΈ, Π² ΠΎΡΠ»ΠΈΡΠΈΠ΅ ΠΎΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΡΠ΅ΡΠ΅Π±ΡΠ°Π»ΡΠ½ΡΠΌΠΈ ΠΌΠ΅ΡΠ°ΡΡΠ°Π·Π°ΠΌΠΈ Π΄ΡΡΠ³ΠΈΡ
Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½- Π½ΡΡ
ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ (ΡΠ°ΠΊ Π»Π΅Π³ΠΊΠΎΠ³ΠΎ, ΠΌΠ΅Π»Π°Π½ΠΎΠΌΠ°, ΠΏΠΎΡΠ΅ΡΠ½ΠΎΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΉ ΡΠ°ΠΊ). Π Π½Π° ΡΠ°Π·Π½ΡΡ
ΡΡΠ°ΠΏΠ°Ρ
ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π±ΠΎΠ»Π΅Π·Π½ΠΈ ΡΡΠΈΠΌ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΊΠ°ΠΌ ΠΌΠΎΠ³ΡΡ Π±ΡΡΡ ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ Π²ΠΈΠ΄Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ: Ρ
ΠΈΠΌΠΈΠΎΡΠ΅ΡΠ°ΠΏΠΈΡ, Π³ΠΎΡΠΌΠΎΠ½ΠΎΡΠ΅ΡΠ°ΠΏΠΈΡ, ΡΠ°ΡΠ³Π΅ΡΠ½Π°Ρ ΡΠ΅ΡΠ°ΠΏΠΈΡ, Π»ΡΡΠ΅Π²Π°Ρ ΡΠ΅ΡΠ°ΠΏΠΈΡ, ΡΠ°Π΄ΠΈΠΎΡ
ΠΈΡΡΡΠ³ΠΈΡ, Ρ
ΠΈΡΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π»Π΅ΡΠ΅Π½ΠΈΠ΅. ΠΠ΄Π½Π°ΠΊΠΎ ΡΡΠ°Π½Π΄Π°ΡΡΠΎΠ² ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΡΡΠΈΡ
ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΈΡ ΠΊ Ρ
ΠΈΡΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΌΡ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΏΡΠΈ ΡΠ΅ΡΠ΅Π±ΡΠ°Π»ΡΠ½ΡΡ
ΠΌΠ΅ΡΠ°ΡΡΠ°Π·Π°Ρ
ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ Π² Π½Π°ΡΡΠΎΡΡΠ΅Π΅ Π²ΡΠ΅ΠΌΡ Π½Π΅Ρ. Π ΡΡΠ°ΡΡΠ΅ ΠΎΠΏΠΈΡΡΠ²Π°ΡΡΡΡ Ρ
ΠΈΡΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ, ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΡΡΡΡ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΈΡ ΠΈ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΏΠΎΠΊΠ°Π·Π°Π½ΠΈΡ ΠΊ Ρ
ΠΈΡΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΌΡ Π»Π΅ΡΠ΅Π½ΠΈΡ
ΠΠ»ΠΈΡΠ½ΠΈΠ΅ Π³ΠΈΠΏΠΎΠΊΡΠΈΠΈ Π½Π° ΡΠ΅ΠΊΡΠ΅ΡΠΎΠΌ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΌΡΠ»ΡΡΠΈΡΠΎΡΠΌΠ½ΠΎΠΉ Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°
Background. Glioblastoma multiforme (GBM) develops in the hypoxic microenvironment, which plays an important role in the pathogenesis of the disease and is closely associated with tumor growth, development and poor prognosis. Hypoxia increases the resistance of tumor cells (TC) to radiation therapy and chemotherapy, promotes the appearance of an aggressive TC phenotype, leading to the disease recurrence. The molecular mechanism of hypoxic action on the secretome of GBM cells, which is involved in the formation of the tumor microenvironment, remains unclear. Also, markers of the aggressive hypoxia-associated phenotype of tumor cells have not been established.Β The purpose of researchΒ β to study the molecular mechanisms of the hypoxia-associated effect on the secretome of the U251 GBM cells.Materials and method. High resolution proteomic mass spectrometry, cell technologies.Results. A total of 1432 proteins were identified in the secretomes of two types of GBM cells (control and experiment). After the action of hypoxia, statistically significant changes in the expression of 390 proteins were registered. 11Β proteins showed increase in expression over two orders of magnitude. The intracellular signaling pathways which are responsible for the hypoxia-associated effects on the U251 GMB cells have been identified.Conclusions. Hypoxia significantly affected the proteomic composition of the GBM cells secretome. Five overexpressed secretome proteins, S100A6, HEY1, ZIP3, S100A4, ZEB2, have been proposed as potential markers of the hypoxiaassociated phenotype of GBM, for which participation in the pathogenesis of glioblastoma multiforme has been previously showed.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠΡΠ»ΡΡΠΈΡΠΎΡΠΌΠ½Π°Ρ Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΠ° (ΠΠΠ) ΡΠ°Π·Π²ΠΈΠ²Π°Π΅ΡΡΡ Π½Π°Β ΡΠΎΠ½Π΅ Π³ΠΈΠΏΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΌΠΈΠΊΡΠΎΡΡΠ΅Π΄Ρ, ΠΈΠ³ΡΠ°ΡΡΠ΅ΠΉ Π²Π°ΠΆΠ½ΡΡ ΡΠΎΠ»Ρ Π²Β ΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΠΈΒ ΡΠ΅ΡΠ½ΠΎ ΡΠ²ΡΠ·Π°Π½Π½ΠΎΠΉ ΡΒ ΡΠΎΡΡΠΎΠΌ ΠΈΒ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ΠΌ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ ΠΈΒ ΠΏΠ»ΠΎΡ
ΠΈΠΌ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΎΠΌ. ΠΠΈΠΏΠΎΠΊΡΠΈΡ (ΠΠ‘) ΠΏΠΎΠ²ΡΡΠ°Π΅Ρ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΡ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ (ΠΠ) ΠΊΒ Π»ΡΡΠ΅Π²ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΈΒ Ρ
ΠΈΠΌΠΈΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ, ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΡΠ΅Ρ ΠΏΠΎΡΠ²Π»Π΅Π½ΠΈΡ Π°Π³ΡΠ΅ΡΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΡΠ΅Π½ΠΎΡΠΈΠΏΠ° ΠΠ, ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠ΅Π³ΠΎ ΠΊΒ ΡΠ΅ΡΠΈΠ΄ΠΈΠ²Ρ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ. ΠΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠ΅ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΡ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΠ‘ Π½Π°Β ΡΠ΅ΠΊΡΠ΅ΡΠΎΠΌ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΠΠ, ΡΡΠ°ΡΡΠ²ΡΡΡΠΈΠΉ Π²Β ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΌΠΈΠΊΡΠΎΠΎΠΊΡΡΠΆΠ΅Π½ΠΈΡ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ, ΠΎΡΡΠ°Π΅ΡΡΡ Π½Π΅Β ΠΈΠ·ΡΡΠ΅Π½Π½ΡΠΌ. ΠΒ Π½Π°ΡΡΠΎΡΡΠ΅Π΅ Π²ΡΠ΅ΠΌΡ ΡΠ°ΠΊΠΆΠ΅ Π½Π΅Β ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Ρ ΠΌΠ°ΡΠΊΠ΅ΡΡ Π°Π³ΡΠ΅ΡΡΠΈΠ²Π½ΠΎΠ³ΠΎ Π³ΠΈΠΏΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠ΅Π½ΠΎΡΠΈΠΏΠ° ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡΒ β ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ
ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ² Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π³ΠΈΠΏΠΎΠΊΡΠΈΠΈ Π½Π°Β ΡΠ΅ΠΊΡΠ΅ΡΠΎΠΌ ΠΊΠ»Π΅ΡΠΎΠΊ U251 ΠΠΠ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈΒ ΠΌΠ΅ΡΠΎΠ΄Ρ: ΠΏΡΠΎΡΠ΅ΠΎΠΌΠ½Π°Ρ ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΠΈΡ Π²ΡΡΠΎΠΊΠΎΠ³ΠΎ ΡΠ°Π·ΡΠ΅ΡΠ΅Π½ΠΈΡ, ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠ΅ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΒ ΡΠ΅ΠΊΡΠ΅ΡΠΎΠΌΠ°Ρ
Π΄Π²ΡΡ
ΡΠΈΠΏΠΎΠ² ΠΊΠ»Π΅ΡΠΎΠΊ ΠΠΠ (ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ ΠΈΒ ΠΎΠΏΡΡΠ°) Π²Β ΡΠ΅Π»ΠΎΠΌ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Ρ 1432 Π±Π΅Π»ΠΊΠ°. ΠΠΎΡΠ»Π΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π³ΠΈΠΏΠΎΠΊΡΠΈΠΈ Π·Π°ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π½Ρ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΡΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ Π²Β ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ 390 Π±Π΅Π»ΠΊΠΎΠ². ΠΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π±ΠΎΠ»Π΅Π΅ ΡΠ΅ΠΌΒ Π½Π°Β Π΄Π²Π° ΠΏΠΎΡΡΠ΄ΠΊΠ° Π½Π°Π±Π»ΡΠ΄Π°Π»ΠΈ ΡΒ 11 ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΎΠ². ΠΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Ρ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠ΅ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΠ΅ ΠΏΡΡΠΈ, ΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΡΠ΅ Π·Π°Β Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Π³ΠΈΠΏΠΎΠΊΡΠΈΠΈ Π½Π°Β ΠΊΠ»Π΅ΡΠΊΠΈ U251 ΠΠΠ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠΈΠΏΠΎΠΊΡΠΈΡ ΠΎΠΊΠ°Π·ΡΠ²Π°Π»Π° Π·Π°ΠΌΠ΅ΡΠ½ΠΎΠ΅ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π½Π°Β ΠΏΡΠΎΡΠ΅ΠΎΠΌΠ½ΡΠΉ ΡΠΎΡΡΠ°Π² ΡΠ΅ΠΊΡΠ΅ΡΠΎΠΌΠ° ΠΊΠ»Π΅ΡΠΎΠΊ ΠΠΠ. ΠΒ ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΡ
ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² Π³ΠΈΠΏΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠ΅Π½ΠΎΡΠΈΠΏΠ° ΠΠΠ ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Ρ 5 Π³ΠΈΠΏΠ΅ΡΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π±Π΅Π»ΠΊΠΎΠ² ΡΠ΅ΠΊΡΠ΅ΡΠΎΠΌΠ°: S100A6, HEY1, ZIP3, S100A4, ZEB2, Π΄Π»ΡΒ ΠΊΠΎΡΠΎΡΡΡ
ΡΠ°Π½Π΅Π΅ Π΄ΠΎΠΊΠ°Π·Π°Π½ΠΎ ΡΡΠ°ΡΡΠΈΠ΅ Π²Β ΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π΅ ΠΌΡΠ»ΡΡΠΈΡΠΎΡΠΌΠ½ΠΎΠΉ Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ
ΠΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΠΏΡΠ΅Π΄ΠΈΠΊΡΠΈΠ²Π½ΡΡ ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² Π² ΡΠΏΠΈΠ½Π½ΠΎΠΌΠΎΠ·Π³ΠΎΠ²ΠΎΠΉ ΠΆΠΈΠ΄ΠΊΠΎΡΡΠΈ Π±ΠΎΠ»ΡΠ½ΡΡ Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΠΎΠΉ
Introduction. GlioblastomaΒ (GB) is not yet curable despite recent advances in the treatment of other malignant solid tumors. The management of GB is based solely on histopathological features, imaging of the tumor and its genomic analysis (somatic mutations in the isocitrate dehydrogenase genes, methylation status of the O6-methylguanine-DNA methyltransferase gene promoter). To adapt the treatment to the most recent tumor evolution, molecular information should be received regularly throughout the course of therapy. However, tumor tissue is often not available for diagnosis as the disease progresses. In this regard, the development of less invasive methods, such as analysis of the proteome of biological fluids of patients, is of particular interest. Cerebrospinal fluid (CSF) is an important source disease biomarkers to monitor the presence and progression of the disease.Aim. To identify proteomic predictive biomarkers in the CSF of patients with GB.Materials and methods. During the study, samples of patientsβ CSF samples, high-resolution proteomic mass spectrometry, modern biochemical methods and bioinformatic technologies were used.Results. For the first time, the analysis of proteomes of CSF samples of patients with GB obtained before and 7 days after the removal of the primary tumor was carried out. Potential biomarkers of GB have been identified. After their validation using open databases, 11 proteomic predictive markers of GB (S100A9,Β S100A8, PLA2G15, PPIB, LTBP2, VIM, LAMB1, STC1, NRP1, COL6A1, HSPA5)Β were selected and their role in the molecular mechanisms of gliomagenesis was assessed. Conclusion. The proposed panel of proteomic predictive CSF biomarkers in GB patients can be further used in the development of test systems for assessing the effectiveness of therapy and early detection of disease relapses.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠΠ»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΠ° (ΠΠ) ΠΏΠΎΠΊΠ° Π½Π΅ΠΈΠ·Π»Π΅ΡΠΈΠΌΠ°, Π½Π΅ΡΠΌΠΎΡΡΡ Π½Π° Π΄ΠΎΡΡΠΈΠΆΠ΅Π½ΠΈΡ Π² ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π΄ΡΡΠ³ΠΈΡ
Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΡΠΎΠ»ΠΈΠ΄Π½ΡΡ
ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ. Π’Π°ΠΊΡΠΈΠΊΠ° Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΠ ΠΎΡΠ½ΠΎΠ²ΡΠ²Π°Π΅ΡΡΡ ΠΈΡΠΊΠ»ΡΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π½Π° Π³ΠΈΡΡΠΎΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΈΠ·Π½Π°ΠΊΠ°Ρ
, ΡΠΎΠΌΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π²ΠΈΠ·ΡΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ ΠΈ Π΅Π΅ Π³Π΅Π½ΠΎΠΌΠ½ΠΎΠΌ Π°Π½Π°Π»ΠΈΠ·Π΅ (ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΡΡΠ°ΡΠΈΠΈ Π² Π³Π΅Π½Π°Ρ
ΠΈΠ·ΠΎΡΠΈΡΡΠ°ΡΠ΄Π΅Π³ΠΈΠ΄ΡΠΎΠ³Π΅Π½Π°Π·Ρ, ΡΡΠ°ΡΡΡ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ° Π³Π΅Π½Π° O6-ΠΌΠ΅ΡΠΈΠ»Π³ΡΠ°Π½ΠΈΠ½-ΠΠΠ-ΠΌΠ΅ΡΠΈΠ»ΡΡΠ°Π½ΡΡΠ΅ΡΠ°Π·Π°). Π΄Π»Ρ Π°Π΄Π°ΠΏΡΠ°ΡΠΈΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΊ ΡΠ°ΠΌΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄Π½Π΅ΠΉ ΡΠ²ΠΎΠ»ΡΡΠΈΠΈ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½Π°Ρ ΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΡ Π΄ΠΎΠ»ΠΆΠ½Π° ΠΏΠΎΡΡΡΠΏΠ°ΡΡ ΡΠ΅Π³ΡΠ»ΡΡΠ½ΠΎ Π½Π° ΠΏΡΠΎΡΡΠΆΠ΅Π½ΠΈΠΈ Π²ΡΠ΅Π³ΠΎ ΠΊΡΡΡΠ° ΡΠ΅ΡΠ°ΠΏΠΈΠΈ. ΠΠ΄Π½Π°ΠΊΠΎ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²Π°Ρ ΡΠΊΠ°Π½Ρ ΡΠ°ΡΡΠΎ Π½Π΅Π΄ΠΎΡΡΡΠΏΠ½Π° Π΄Π»Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΏΡΠΈ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ. Π² ΡΠ²ΡΠ·ΠΈ Ρ ΡΡΠΈΠΌ Π°ΠΊΡΡΠ°Π»ΡΠ½ΠΎΠΉ ΡΡΠ°Π½ΠΎΠ²ΠΈΡΡΡ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ° ΠΌΠ΅Π½Π΅Π΅ ΠΈΠ½Π²Π°Π·ΠΈΠ²Π½ΡΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ², Π½Π°ΠΏΡΠΈΠΌΠ΅Ρ Π°Π½Π°Π»ΠΈΠ·Π° ΠΏΡΠΎΡΠ΅ΠΎΠΌΠ° Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΆΠΈΠ΄ΠΊΠΎΡΡΠ΅ΠΉ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ². ΠΡΠΎΠ±ΡΠΉ ΠΈΠ½ΡΠ΅ΡΠ΅Ρ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅Ρ ΡΠΏΠΈΠ½Π½ΠΎΠΌΠΎΠ·Π³ΠΎΠ²Π°Ρ ΠΆΠΈΠ΄ΠΊΠΎΡΡΡ (Π‘ΠΠ) β Π²Π°ΠΆΠ½ΡΠΉ ΠΈΡΡΠΎΡΠ½ΠΈΠΊ Π±ΠΈΠΎΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ Π΄Π»Ρ ΠΌΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³Π° Π½Π°Π»ΠΈΡΠΈΡ ΠΈ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΠΏΡΠΎΡΠ΅ΠΎΠΌΠ½ΡΡ
ΠΏΡΠ΅Π΄ΠΈΠΊΡΠΈΠ²Π½ΡΡ
Π±ΠΈΠΎΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² Π² Π‘ΠΠ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΠ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. Π Ρ
ΠΎΠ΄Π΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π±ΡΠ»ΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½Ρ ΠΎΠ±ΡΠ°Π·ΡΡ Π‘ΠΠ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΏΡΠΎΡΠ΅ΠΎΠΌΠ½Π°Ρ ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΠΈΡ Π²ΡΡΠΎΠΊΠΎΠ³ΠΎ ΡΠ°Π·ΡΠ΅ΡΠ΅Π½ΠΈΡ, ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ Π±ΠΈΠΎΡ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΈ Π±ΠΈΠΎΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠΏΠ΅ΡΠ²ΡΠ΅ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ Π°Π½Π°Π»ΠΈΠ· ΠΏΡΠΎΡΠ΅ΠΎΠΌΠΎΠ² ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² Π‘ΠΠ Π±ΠΎΠ»ΡΠ½ΡΡ
Β ΠΠ, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
Π΄ΠΎ ΠΈ ΡΠΏΡΡΡΡ 7 Π΄Π½Π΅ΠΉ ΠΏΠΎΡΠ»Π΅ ΡΠ΄Π°Π»Π΅Π½ΠΈΡ ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΠΎΠΉ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ. ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½ΡΒ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΠ΅ Π±ΠΈΠΎΠΌΠ°ΡΠΊΠ΅ΡΡ ΠΠ. ΠΏΠΎΡΠ»Π΅ ΠΈΡ
Π²Π°Π»ΠΈΠ΄Π°ΡΠΈΠΈ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΎΡΠΊΡΡΡΡΡ
Π±Π°Π· Π΄Π°Π½Π½ΡΡ
ΠΎΡΠΎΠ±ΡΠ°Π½Ρ 11 ΠΏΡΠΎΡΠ΅ΠΎΠΌΠ½ΡΡ
ΠΏΡΠ΅Π΄ΠΈΠΊΡΠΈΠ²Π½ΡΡ
ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² ΠΠ (S100A9, S100A8, PLA2G15, PPIB,Β LTBP2, VIM, LAMB1, STC1, NRP1, COL6A1, HSPA5)Β ΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π° ΠΎΡΠ΅Π½ΠΊΠ° ΠΈΡ
ΡΠΎΠ»ΠΈ Π² ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ
ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠ°Ρ
Π³Π»ΠΈΠΎΠΌΠ°Π³Π΅Π½Π΅Π·Π°.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π½Π°Ρ ΠΏΠ°Π½Π΅Π»Ρ ΠΏΡΠΎΡΠ΅ΠΎΠΌΠ½ΡΡ
ΠΏΡΠ΅Π΄ΠΈΠΊΡΠΈΠ²Π½ΡΡ
Π±ΠΈΠΎΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² Π‘ΠΠ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΠ ΠΌΠΎΠΆΠ΅Ρ Π² Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ΅ΠΌ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°ΡΡΡΡ ΠΏΡΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ΅ ΡΠ΅ΡΡ-ΡΠΈΡΡΠ΅ΠΌ Π΄Π»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΈ ΡΠ°Π½Π½Π΅Π³ΠΎ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΡΠ΅ΡΠΈΠ΄ΠΈΠ²ΠΎΠ² Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ
ΠΠ΅ΡΠ΅ΡΠΌΠΈΠ½Π°Π½ΡΡ ΡΠ΅ΡΡΠΎΠΏΡΠΎΠ·Π° - ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΠ΅ ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠΈΡΠ΅Π½ΠΈ ΡΡΠ²ΠΎΠ»ΠΎΠ²ΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ
Introduction. Treatment of glioblastoma multiforme remains little effective due to the rapidly developing recurrence of the tumor, due to its high tumorigenic potential, resistance to chemoradiation therapy and increased dissemination of glioma stem cells. The identification of potential therapeutic targets, which make it possible to more effectively destroy glioma stem cells, becomes topical. In this regard, the study of ferroptosis (FP), which can cause the death of tumor cells with a highly malignant phenotype, is of great importance. However, FP and its regulatory pathways in the GSC are not fully understood. At present, it is also not clear how FP differs for glioma stem cells and glioblastoma differentiated cells.Aim. To study the expression of ferroptosis signaling cascade determinants in CD133+ glioma stem cells and CD133- glioblastoma differentiated cells using high resolution proteomic mass spectrometry.Materials and methods. High-resolution proteomic mass spectrometry, cell technologies.Results. In total, 1970 proteins were identified, 15 of which are associated with ferroptosis and are present in both cell populations. Upregulation of 12 FP determinants (ACSL1, ACSL3, COPZ1, FTH1, FTL, GPX1, GPX4, PCBP1, SLC3A2, TFRC, VDAC1, VDAC2) was found in CD133+ glioblastoma stem cells compared to CD133- differential glioblastoma cells, 10 of which were more than 2-fold overexpressed.Conclusion. Important regularities have been established in the expression of ferroptosis determinants and proteins controlling this process in glioma stem cells, which can be used in the development of new approaches to the detection of potential targets for the therapy of glioblastoma multiforme.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. Π’Π΅ΡΠ°ΠΏΠΈΡ ΠΌΡΠ»ΡΡΠΈΡΠΎΡΠΌΠ½ΠΎΠΉ Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ ΠΎΡΡΠ°Π΅ΡΡΡ ΠΌΠ°Π»ΠΎΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠΉ ΠΈΠ·-Π·Π° Π±ΡΡΡΡΠΎΡΠ°Π·Π²ΠΈΠ²Π°ΡΡΠΈΡ
ΡΡ ΡΠ΅ΡΠΈΠ΄ΠΈΠ²ΠΎΠ² ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ, ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΡ
Π²ΡΡΠΎΠΊΠΈΠΌ ΡΡΠΌΠΎΡΠΎΠ³Π΅Π½Π½ΡΠΌ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΠΎΠΌ, ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΡΡ ΠΊ Ρ
ΠΈΠΌΠΈΠΎΠ»ΡΡΠ΅Π²ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΈ ΠΏΠΎΠ²ΡΡΠ΅Π½Π½ΠΎΠΉ Π΄ΠΈΡΡΠ΅ΠΌΠΈΠ½Π°ΡΠΈΠ΅ΠΉ ΡΡΠ²ΠΎΠ»ΠΎΠ²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ. ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΠΉ ΡΡΠ°Π½ΠΎΠ²ΠΈΡΡΡ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΡ
ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΌΠΈΡΠ΅Π½Π΅ΠΉ, ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡΠΈΡ
Π±ΠΎΠ»Π΅Π΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎ ΡΠ½ΠΈΡΡΠΎΠΆΠ°ΡΡ Π΄Π°Π½Π½ΡΠ΅ ΠΊΠ»Π΅ΡΠΊΠΈ. Π² ΡΠ²ΡΠ·ΠΈ Ρ ΡΡΠΈΠΌ Π±ΠΎΠ»ΡΡΠΎΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ ΠΏΡΠΈΠΎΠ±ΡΠ΅ΡΠ°Π΅Ρ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΡΠ΅ΡΡΠΎΠΏΡΠΎΠ·Π° (Π€Π), ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΠ³ΠΎ Π²ΡΠ·ΡΠ²Π°ΡΡ Π³ΠΈΠ±Π΅Π»Ρ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ Ρ Π²ΡΡΠΎΠΊΠΎΠ·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠΌ ΡΠ΅Π½ΠΎΡΠΈΠΏΠΎΠΌ. ΠΠ΄Π½Π°ΠΊΠΎ Π€Π ΠΈ Π΅Π³ΠΎ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΠ΅ ΠΏΡΡΠΈ Π² ΡΡΠ²ΠΎΠ»ΠΎΠ²ΡΡ
ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ Π΄ΠΎ ΠΊΠΎΠ½ΡΠ° Π½Π΅ ΠΈΠ·ΡΡΠ΅Π½Ρ. Π² Π½Π°ΡΡΠΎΡΡΠ΅Π΅ Π²ΡΠ΅ΠΌΡ ΡΠ°ΠΊΠΆΠ΅ Π½Π΅ ΡΡΠ½ΠΎ, ΡΠ΅ΠΌ ΠΎΡΠ»ΠΈΡΠ°Π΅ΡΡΡ Π€Π Π² ΡΡΠ²ΠΎΠ»ΠΎΠ²ΡΡ
ΠΈ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ - ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΡΠΎΡΠ΅ΠΎΠΌΠ½ΠΎΠΉ ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΠΈΠΈ Π²ΡΡΠΎΠΊΠΎΠ³ΠΎ ΡΠ°Π·ΡΠ΅ΡΠ΅Π½ΠΈΡ ΠΈΠ·ΡΡΠΈΡΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ Π΄Π΅ΡΠ΅ΡΠΌΠΈΠ½Π°Π½Ρ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠΊΠ°Π΄Π° Π€Π Π² CD133+-ΡΡΠ²ΠΎΠ»ΠΎΠ²ΡΡ
ΠΈ CD133--Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π»ΠΈΡΡ ΠΏΡΠΎΡΠ΅ΠΎΠΌΠ½Π°Ρ ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΠΈΡ Π²ΡΡΠΎΠΊΠΎΠ³ΠΎ ΡΠ°Π·ΡΠ΅ΡΠ΅Π½ΠΈΡ ΠΈ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠ΅ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π² ΡΠ΅Π»ΠΎΠΌ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Ρ 1970 Π±Π΅Π»ΠΊΠΎΠ², 15 ΠΈΠ· ΠΊΠΎΡΠΎΡΡΡ
ΡΠ²ΡΠ·Π°Π½Ρ Ρ Π€Π ΠΈ ΠΏΡΠΈΡΡΡΡΡΠ²ΡΡΡ Π² ΠΎΠ±Π΅ΠΈΡ
ΠΏΠΎΠΏΡΠ»ΡΡΠΈΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ. ΠΠ±Π½Π°ΡΡΠΆΠ΅Π½Π° ΠΏΠΎΠ»ΠΎΠΆΠΈΡΠ΅Π»ΡΠ½Π°Ρ ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ 12 Π΄Π΅ΡΠ΅ΡΠΌΠΈΠ½Π°Π½Ρ Π€Π (ACSL1, ACSL3, COPZ1, FTH1, FTL, GPX1, GPX4, PCBP1, SLC3A2, TFRC, VDAC1, VDAC2) Π² CD133+-ΡΡΠ²ΠΎΠ»ΠΎΠ²ΡΡ
ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ CD133- -Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌΠΈ ΠΊΠ»Π΅ΡΠΊΠ°ΠΌΠΈ Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ, 10 ΠΈΠ· ΠΊΠΎΡΠΎΡΡΡ
ΠΈΠΌΠ΅Π»ΠΈ ΠΏΠΎΠ²ΡΡΠ΅Π½Π½ΡΡ Π±ΠΎΠ»Π΅Π΅ ΡΠ΅ΠΌ Π² 2 ΡΠ°Π·Π° ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Ρ Π²Π°ΠΆΠ½ΡΠ΅ Π·Π°ΠΊΠΎΠ½ΠΎΠΌΠ΅ΡΠ½ΠΎΡΡΠΈ Π² ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π΄Π΅ΡΠ΅ΡΠΌΠΈΠ½Π°Π½Ρ Π€Π ΠΈ ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΎΠ², ΠΊΠΎΠ½ΡΡΠΎΠ»ΠΈΡΡΡΡΠΈΡ
ΡΡΠΎΡ ΠΏΡΠΎΡΠ΅ΡΡ Π² ΡΡΠ²ΠΎΠ»ΠΎΠ²ΡΡ
ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ, ΠΊΠΎΡΠΎΡΡΠ΅ ΠΌΠΎΠ³ΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°ΡΡΡΡ ΠΏΡΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ΅ Π½ΠΎΠ²ΡΡ
ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΎΠ² ΠΊ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΈΡ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΡ
ΠΌΠΈΡΠ΅Π½Π΅ΠΉ Π΄Π»Ρ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΌΡΠ»ΡΡΠΈΡΠΎΡΠΌΠ½ΠΎΠΉ Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ
ΠΠΠΠΠ Π‘Π’ΠΠΠΠΠΠ― Π’ΠΠ ΠΠΠΠ― ΠΠΠΠ¬ΠΠ«Π₯ Π ΠΠΠΠ ΠΠΠΠΠ§ΠΠΠ ΠΠΠΠΠΠ« C ΠΠΠ’ΠΠ‘Π’ΠΠ’ΠΠ§ΠΠ‘ΠΠΠ ΠΠΠ ΠΠΠΠΠΠΠ ΠΠΠΠΠΠΠΠΠ ΠΠΠΠΠ
The Blokhin RCRC the effectiveness of various schemes of drug therapy in breast cancer patients with brain metastases was evaluated.When using the schemes with anthracyclines (CAF, AC) among 26 patients objective response in the brain (full and partial regression) was registered in 16 (62%) patients (previously untreated patients). Median survival was 12 months. In the group of patients received monotherapy (30 patients), capecitabine was administered at a dose of 2000 mg/m2/day per os the 1 to 14 days every 3 weeks. Partial effect in the brain was registered in 9 patients (30%). Median survival was 15.1 months. In the combination therapy group (capecitabine + radiotherapy) among 30 patients overall effect in the brain was registered in 4 patients (13%), partial response - 18 (60%). Median survival was 22 months. The effectiveness of chemotherapy scheme gemcitabine and cisplatin in 30 breast cancer patients with metastases in the brain, previously treated with I-III line of chemotherapy and radiation therapy in the area of the brain was evaluated. In 4 cases (13.3%) complete regression of metastases in the brain was achieved. In 12 patients (40.0%) a partial regression of metastases in the brain was achieved. Median survival was 10 months. Twenty-three breast cancer patients with overexpression of Her2/neu, and with metastatic brain lesions received capecitabine + lapatinib. Complete response in the brain was achieved in 2 cases (8.7%), partial regression - in 9 cases (39.1%) and stabilization of the disease - in 10 cases (43.5%). Median overall survival was 16 months. Nine patients with breast cancer with overexpression of Her2/neu, and with metastatic brain lesions received therapy with capecitabine + trastuzumab. In 2 cases (22.2%) complete regression of metastases in the brain was achieved, in 4 cases (44.4%) - partial response, in 2 cases (22.2%) - stabilization. The median overall survival was 15.5 months.Thus, the results of this study have shown high efficiency of drug therapy in the treatment of breast cancer patients with metastases in the brain.Π Π ΠΠΠ¦ ΠΈΠΌ Π. Π. ΠΠ»ΠΎΡ
ΠΈΠ½Π° Π ΠΠΠ ΠΈΠ·ΡΡΠ°Π»Π°ΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Β ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΡΡ
Π΅ΠΌ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΠΎΠΉ Β ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ ΠΌΠ΅ΡΠ°ΡΡΠ°Π·Π°ΠΌΠΈ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ Π² Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠΌ ΠΌΠΎΠ·Π³Π΅.ΠΡΠΈ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠΈ ΡΡ
Π΅ΠΌ Ρ Π°Π½ΡΡΠ°ΡΠΈΠΊΠ»ΠΈΠ½Π°ΠΌΠΈ (CAF, AC) Ρ 26 Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΎΠ±ΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠΉ ΡΡΡΠ΅ΠΊΡ Π² ΠΌΠΎΠ·Π³Π΅ (ΠΏΠΎΠ»Π½ΡΠ΅ ΠΈ ΡΠ°ΡΡΠΈΡΠ½ΡΠ΅ ΡΠ΅Π³ΡΠ΅ΡΡΠΈΠΈ) Π·Π°ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π½ Β Ρ 16 (62%) ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠΊ (ΡΠ°Π½Π΅Π΅ Π½Π΅Π»Π΅ΡΠ΅Π½ΡΠ΅ Π±ΠΎΠ»ΡΠ½ΡΠ΅). ΠΠ΅Π΄ΠΈΠ°Π½Π° Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ Π±ΠΎΠ»ΡΠ½ΡΡ
ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 12 ΠΌΠ΅ΡΡΡΠ΅Π². Π Π³ΡΡΠΏΠΏΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
ΠΌΠΎΠ½ΠΎΡΠ΅ΡΠ°ΠΏΠΈΡ (30 ΡΠ΅Π»ΠΎΠ²Π΅ΠΊ), ΠΊΠ°ΠΏΠ΅ΡΠΈΡΠ°Π±ΠΈΠ½ Π½Π°Π·Π½Π°ΡΠ°Π»ΡΡΒ Π² Π΄ΠΎΠ·Π΅ 2000 ΠΌΠ³/ΠΌ2/ΡΡΡΠΊΠΈ Π²Π½ΡΡΡΡ Ρ 1 ΠΏΠΎ 14 Π΄Π½ΠΈ, ΠΊΠ°ΠΆΠ΄ΡΠ΅ 3 Π½Π΅Π΄Π΅Π»ΠΈ. Β Π§Π°ΡΡΠΈΡΠ½ΡΠΉ ΡΡΡΠ΅ΠΊΡ Π² Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠΌ ΠΌΠΎΠ·Π³Π΅ Π·Π°ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π½ Β Ρ 9 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠΊ (30%). ΠΠ΅Π΄ΠΈΠ°Π½Π° Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 15,1 ΠΌΠ΅ΡΡΡΠ°. Π Π³ΡΡΠΏΠΏΠ΅ ΠΊΠΎΠΌΠ±ΠΈΠ½ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ Β ΡΠ΅ΡΠ°ΠΏΠΈΠΈ (ΠΊΠ°ΠΏΠ΅ΡΠΈΡΠ°Π±ΠΈΠ½ + Π»ΡΡΠ΅Π²Π°Ρ ΡΠ΅ΡΠ°ΠΏΠΈΡ) ΠΈΠ· 30 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² ΠΏΠΎΠ»Π½ΡΠΉ ΡΡΡΠ΅ΠΊΡ Π² Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠΌ ΠΌΠΎΠ·Π³Π΅ Π·Π°ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π½ Ρ 4 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠΊ (13%), ΡΠ°ΡΡΠΈΡΠ½ΡΠΉ ΡΡΡΠ΅ΠΊΡ β Ρ 18 (60%). ΠΠ΅Π΄ΠΈΠ°Π½Π° Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 22 ΠΌΠ΅ΡΡΡΠ°. ΠΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΎΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Β ΠΏΠΎ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Ρ
ΠΈΠΌΠΈΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΠΏΠΎ ΡΡ
Π΅ΠΌΠ΅ Π³Π΅ΠΌΡΠΈΡΠ°Π±ΠΈΠ½ + ΡΠΈΡΠΏΠ»Π°ΡΠΈΠ½ Ρ 30 Π±ΠΎΠ»ΡΠ½ΡΡ
ΡΠ°ΠΊΠΎΠΌ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ Ρ ΠΌΠ΅ΡΠ°ΡΡΠ°Π·Π°ΠΌΠΈ Π² Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠΌ ΠΌΠΎΠ·Π³Π΅, Β ΡΠ°Π½Π΅Π΅ Β ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
IβIII Π»ΠΈΠ½ΠΈΠΈ Ρ
ΠΈΠΌΠΈΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ Β ΠΈ Π»ΡΡΠ΅Π²ΡΡ ΡΠ΅ΡΠ°ΠΏΠΈΡ Π½Π° ΠΎΠ±Π»Π°ΡΡΡ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π°. Π 4 ΡΠ»ΡΡΠ°ΡΡ
(13,3%) Π΄ΠΎΡΡΠΈΠ³Π½ΡΡΠ° ΠΏΠΎΠ»Π½Π°Ρ ΡΠ΅Π³ΡΠ΅ΡΡΠΈΡ Β ΠΌΠ΅ΡΠ°ΡΡΠ°Π·ΠΎΠ² Π² Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠΌ ΠΌΠΎΠ·Π³Π΅. Π£ 12 Π±ΠΎΠ»ΡΠ½ΡΡ
(40,0%) Π΄ΠΎΡΡΠΈΠ³Π½ΡΡΠ° ΡΠ°ΡΡΠΈΡΠ½Π°Ρ ΡΠ΅Π³ΡΠ΅ΡΡΠΈΡ Β ΠΌΠ΅ΡΠ°ΡΡΠ°Π·ΠΎΠ² Π² Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠΌ ΠΌΠΎΠ·Π³Π΅. ΠΠ΅Π΄ΠΈΠ°Π½Π° ΠΎΠ±ΡΠ΅ΠΉ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 10 ΠΌΠ΅Ρ. 23 Π±ΠΎΠ»ΡΠ½ΡΠΌ ΡΠ°ΠΊΠΎΠΌ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ Ρ Π³ΠΈΠΏΠ΅ΡΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠ΅ΠΉ Her-2/neu ΠΈ c ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΏΠΎΡΠ°ΠΆΠ΅Π½ΠΈΠ΅ΠΌ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π° ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»Π°ΡΡ ΡΠ΅ΡΠ°ΠΏΠΈΡ ΠΏΠΎ ΡΡ
Π΅ΠΌΠ΅ ΠΊΠ°ΠΏΠ΅ΡΠΈΡΠ°Π±ΠΈΠ½ + Π»Π°ΠΏΠ°ΡΠΈΠ½ΠΈΠ±. Β Π 2 ΡΠ»ΡΡΠ°ΡΡ
(8,7%) Π΄ΠΎΡΡΠΈΠ³Π½ΡΡΠ° ΠΏΠΎΠ»Π½Π°Ρ ΡΠ΅Π³ΡΠ΅ΡΡΠΈΡ Β Π² Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠΌ ΠΌΠΎΠ·Π³Π΅, Π² 9 ΡΠ»ΡΡΠ°ΡΡ
(39,1%) β ΡΠ°ΡΡΠΈΡΠ½Π°Ρ ΡΠ΅Π³ΡΠ΅ΡΡΠΈΡ, Π² 10 ΡΠ»ΡΡΠ°ΡΡ
(43,5%) β ΡΡΠ°Π±ΠΈΠ»ΠΈΠ·Π°ΡΠΈΡ Π±ΠΎΠ»Π΅Π·Π½ΠΈ. ΠΠ΅Π΄ΠΈΠ°Π½Π° ΠΎΠ±ΡΠ΅ΠΉ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 16 ΠΌΠ΅ΡΡΡΠ΅Π². 9 Π±ΠΎΠ»ΡΠ½ΡΠΌ ΡΠ°ΠΊΠΎΠΌ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ Ρ Π³ΠΈΠΏΠ΅ΡΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠ΅ΠΉ Her-2/neu ΠΈ c ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΏΠΎΡΠ°ΠΆΠ΅Π½ΠΈΠ΅ΠΌ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π° ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»Π°ΡΡ ΡΠ΅ΡΠ°ΠΏΠΈΡ ΠΏΠΎ ΡΡ
Π΅ΠΌΠ΅ ΠΊΠ°ΠΏΠ΅ΡΠΈΡΠ°Π±ΠΈΠ½ + ΡΡΠ°ΡΡΡΠ·ΡΠΌΠ°Π±. Β Π 2 ΡΠ»ΡΡΠ°ΡΡ
(22,2%) Π·Π°ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π½Π° Β ΠΏΠΎΠ»Π½Π°Ρ ΡΠ΅Π³ΡΠ΅ΡΡΠΈΡ Β ΠΌΠ΅ΡΠ°ΡΡΠ°Π·ΠΎΠ² Π² Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠΌ ΠΌΠΎΠ·Π³Π΅, Π² 4 ΡΠ»ΡΡΠ°ΡΡ
(44,4%) β ΡΠ°ΡΡΠΈΡΠ½Π°Ρ ΡΠ΅Π³ΡΠ΅ΡΡΠΈΡ, Β Π² 2 ΡΠ»ΡΡΠ°ΡΡ
(22,2%) β ΡΡΠ°Π±ΠΈΠ»ΠΈΠ·Π°ΡΠΈΡ. ΠΠ΅Π΄ΠΈΠ°Π½Π° ΠΎΠ±ΡΠ΅ΠΉ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 15,5 ΠΌΠ΅ΡΡΡΠ΅Π².Π’Π°ΠΊΠΈΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ, Β ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½ΡΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ Π²ΡΡΠΎΠΊΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π² Π»Π΅ΡΠ΅Π½ΠΈΠΈ Π±ΠΎΠ»ΡΠ½ΡΡ
ΡΠ°ΠΊΠΎΠΌ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ Ρ ΠΌΠ΅ΡΠ°ΡΡΠ°Π·Π°ΠΌΠΈ Π² Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠΌ ΠΌΠΎΠ·Π³Π΅
ΠΠΠΠΠΠΠΠ£ΠΠΠΠΠΠ¦ΠΠ― ΠΠΠ§ΠΠΠΠ― ΠΠΠ¦ΠΠΠΠ’ΠΠ Π‘ Π¦ΠΠ ΠΠΠ ΠΠΠ¬ΠΠ«ΠΠ ΠΠΠ’ΠΠ‘Π’ΠΠΠΠΠ ΠΠΠΠΠΠ§ΠΠ‘Π’ΠΠΠΠΠ«Π₯ ΠΠΠ£Π₯ΠΠΠΠ. ΠΠ ΠΠΠΠΠ‘Π’ΠΠ§ΠΠ‘ΠΠΠ― Π¨ΠΠΠΠ TUNS
Improvement in the diagnosis and treatment of cancer patients, increase in frequency of prevalence and detection of metastatic lesions of the brain make the choice of treatment timely and important. The article presents data on the current prognostic scales for patients with cerebral metastases of solid tumors and the analysis of their features. The features of choice of tactics and strategy of treatment of patients with cerebral metastases of solid tumors depending on various prognostic factors are described. The original version of the rating scale for determining treatment options for patients with metastatic brain lesions is proposed. We suggest to consider oncological, neurological (neurosurgical), somatic (functional) groups of factors to choose the tactics of treatment of patients with brain metastases.Π‘ΠΎΠ²Π΅ΡΡΠ΅Π½ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΠ΅ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΡΠΎΡΡ ΡΠ°ΡΡΠΎΡΡ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΠΎΡΡΠΈ ΠΈ Π²ΡΡΠ²Π»ΡΠ΅ΠΌΠΎΡΡΠΈ ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΠΎΡΠ°ΠΆΠ΅Π½ΠΈΡ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π° Π΄Π΅Π»Π°ΡΡ Π²ΠΎΠΏΡΠΎΡ Π²ΡΠ±ΠΎΡΠ° Π»Π΅ΡΠ΅Π½ΠΈΡ ΡΠ²ΠΎΠ΅Π²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠΌ ΠΈ Π²Π°ΠΆΠ½ΡΠΌ. Π ΡΡΠ°ΡΡΠ΅ ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΡΡ Π΄Π°Π½Π½ΡΠ΅ ΠΎ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ
ΠΏΡΠΎΠ³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠΊΠ°Π»Π°Ρ
Π΄Π»Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΡΠ΅ΡΠ΅Π±ΡΠ°Π»ΡΠ½ΡΠΌΠΈ ΠΌΠ΅ΡΠ°ΡΡΠ°Π·Π°ΠΌΠΈ ΡΠΎΠ»ΠΈΠ΄Π½ΡΡ
ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ. ΠΡΠΎΠ²ΠΎΠ΄ΠΈΡΡΡ Π°Π½Π°Π»ΠΈΠ· ΠΈΡ
ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠ΅ΠΉ. ΠΠΏΠΈΡΡΠ²Π°ΡΡΡΡ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ Π²ΡΠ±ΠΎΡΠ° ΡΠ°ΠΊΡΠΈΠΊΠΈ ΠΈ ΡΡΡΠ°ΡΠ΅Π³ΠΈΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΡΠ΅ΡΠ΅Π±ΡΠ°Π»ΡΠ½ΡΠΌΠΈ ΠΌΠ΅ΡΠ°ΡΡΠ°Π·Π°ΠΌΠΈ ΡΠΎΠ»ΠΈΠ΄Π½ΡΡ
ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΏΡΠΎΠ³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ°ΠΊΡΠΎΡΠΎΠ². ΠΡΠ΅Π΄Π»Π°Π³Π°Π΅ΡΡΡ ΠΎΡΠΈΠ³ΠΈΠ½Π°Π»ΡΠ½ΡΠΉ Π²Π°ΡΠΈΠ°Π½Ρ ΠΎΡΠ΅Π½ΠΎΡΠ½ΠΎΠΉ ΡΠΊΠ°Π»Ρ Π΄Π»Ρ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠ΅ΠΉ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ° Ρ ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΏΠΎΡΠ°ΠΆΠ΅Π½ΠΈΠ΅ΠΌ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π°. ΠΠ»Ρ Π²ΡΠ±ΠΎΡΠ° ΡΠ°ΠΊΡΠΈΠΊΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΌΠ΅ΡΠ°ΡΡΠ°Π·Π°ΠΌΠΈ Π² Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠΉ ΠΌΠΎΠ·Π³ ΠΏΡΠ΅Π΄Π»Π°Π³Π°Π΅ΡΡΡ ΡΡΠΈΡΡΠ²Π°ΡΡ Π³ΡΡΠΏΠΏΡ ΡΠ°ΠΊΡΠΎΡΠΎΠ²: ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅, Π½Π΅Π²ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ (Π½Π΅ΠΉΡΠΎΡ
ΠΈΡΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅), ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ (ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΠ΅)
ΠΠΠ’/ΠΠ’ Ρ 18F-Π€ΠΠ’ Π² Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ΅ ΡΠ΅ΡΠΈΠ΄ΠΈΠ²ΠΎΠ² ΠΈ ΠΏΠΎΡΡΠ»ΡΡΠ΅Π²ΡΡ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ ΠΏΡΠΈ ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΌ ΠΏΠΎΡΠ°ΠΆΠ΅Π½ΠΈΠΈ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π°
Summary. Evaluation of the potential of PET/CT withΒ 18F-FET in differential diagnosis recurrence from post-radiationΒ changes in patients with metastatic brain lesions afterΒ stereotactic radiosurgery.Materials and methods. The study included resultsΒ of PET/CT with 18F-FET and MRI studies of 23 patients withΒ brain metastases of primary tumors different localizationΒ after Gamma knife. Number of lesions in which was measuredΒ quantitative indicators were 48. All patients underwentΒ three-phase PET/CT with 18F-FET and at least two dynamicΒ MRI. PET/CT was performed in three stages: the first immediatelyΒ after administration of 18F-FET, the second and third in 10 and 40 min after administration respectively. The data were evaluated visually with calculation of maxSUV1,2,3 and TBR1,2,3 respectively to the three phases of the studies.Β Results. Accumulation of 18F-FET in the pathologicalΒ lesions in the majority of cases (98%) were characterized byΒ higher values of maxSUV1,2,3 relatively to the unaffected substanceΒ of the brain and only in one case the accumulationΒ did not exceed background. The average values of theΒ TBR1,2,3 were higher in the recurrence of metastases than inΒ mixed and radiation necrosis changes. Determined the significanceΒ of the first stage of the scan with calculation TBR1Β β values in the recurrence were higher than 2.0, than mixedΒ changes and necrosis values that were below 2.0. AdditionalΒ information gives graphical analysis of dynamics of TBR1,2,3,Β which also allows to differentiate mixed changes and postradiationΒ necrosis by the vector curve.Conclusion. Comprehensive analysis of TBR1 valuesΒ and curve type are more accurate criteria than single analysisΒ maxSUV1,2,3 in the pathological area. In case of recurrenceΒ it is possible to determine the most active site, whichΒ plays an important role in planning for repeated radiosurgery.Β Identification of the mixed nature of changes haveΒ a predictive character and, in most cases, involve dynamicΒ control.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ: ΠΎΡΠ΅Π½ΠΊΠ° Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠ΅ΠΉ ΠΠΠ’/ΠΠ’Β Ρ 18F-Π€ΠΠ’ Π² Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ΅ ΡΠ΅ΡΠΈΠ΄ΠΈΠ²ΠΎΠ²Β ΠΎΡ ΠΏΠΎΡΡΠ»ΡΡΠ΅Π²ΡΡ
ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌΒ ΠΏΠΎΡΠ°ΠΆΠ΅Π½ΠΈΠ΅ΠΌ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π° ΠΏΠΎΡΠ»Π΅ ΡΡΠ΅ΡΠ΅ΠΎΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠΉΒ ΡΠ°Π΄ΠΈΠΎΡ
ΠΈΡΡΡΠ³ΠΈΠΈ (Π‘Π Π₯).ΠΠ°ΡΠ΅ΡΠΈΠ°Π» ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. Π ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π±ΡΠ»ΠΈ Π²ΠΊΠ»ΡΡΠ΅Π½Ρ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΠΠ’/ΠΠ’ Ρ 18F-Π€ΠΠ’ ΠΈ ΠΠ Π’-ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉΒ 23 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΌΠ΅ΡΠ°ΡΡΠ°Π·Π°ΠΌΠΈ Π² Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠΌ ΠΌΠΎΠ·Π³Π΅ ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉΒ ΡΠ°Π·Π»ΠΈΡΠ½ΠΎΠΉ ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΠΎΠΉ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΏΠΎΡΠ»Π΅ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½ΠΎΠΉΒ Π‘Π Π₯ Π½Π° Π°ΠΏΠΏΠ°ΡΠ°ΡΠ΅ ΠΠ°ΠΌΠΌΠ°-Π½ΠΎΠΆ. ΠΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΎΡΠ°Π³ΠΎΠ², Π² ΠΊΠΎΡΠΎΡΡΡ
Π±ΡΠ»ΠΈ ΠΈΠ·ΠΌΠ΅ΡΠ΅Π½Ρ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠ΅Β ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΠΈ, ΡΠΎΡΡΠ°Π²ΠΈΠ»ΠΎ 48. ΠΡΠ΅ΠΌ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ°ΠΌ Π±ΡΠ»Π° Π²ΡΠΏΠΎΠ»Π½Π΅Π½Π° ΡΡΠ΅Ρ
ΡΡΠ°ΠΏΠ½Π°Ρ ΠΠΠ’/ΠΠ’ Ρ 18F-Π€ΠΠ’ ΠΈ ΠΌΠΈΠ½ΠΈΠΌΡΠΌ Π΄Π²Π°Β ΠΠ -ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π² Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΠ΅. ΠΠΠ’/ΠΠ’ Π±ΡΠ»Π° Π²ΡΠΏΠΎΠ»Π½Π΅Π½Π°Β Π² ΡΡΠΈ ΡΡΠ°ΠΏΠ°: ΠΏΠ΅ΡΠ²ΡΠΉ β ΡΡΠ°Π·Ρ ΠΏΠΎΡΠ»Π΅ Π²Π½ΡΡΡΠΈΠ²Π΅Π½Π½ΠΎΠ³ΠΎ Π²Π²Π΅Π΄Π΅Π½ΠΈΡ 18F-Π€ΠΠ’, Π²ΡΠΎΡΠΎΠΉ ΠΈ ΡΡΠ΅ΡΠΈΠΉ ΡΡΠ°ΠΏΡ ΡΠ΅ΡΠ΅Π· 10 ΠΈ 40 ΠΌΠΈΠ½Β ΠΎΡ ΠΌΠΎΠΌΠ΅Π½ΡΠ° Π²Π²Π΅Π΄Π΅Π½ΠΈΡ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ. ΠΠ°Π½Π½ΡΠ΅ ΠΎΡΠ΅Π½ΠΈΠ²Π°Π»ΠΈΡΡ Π²ΠΈΠ·ΡΠ°Π»ΡΠ½ΠΎ ΠΈ Ρ ΠΏΠΎΠ΄ΡΡΠ΅ΡΠΎΠΌ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ maxSUV1,2,3 ΠΈΒ TBR1,2,3 ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ ΡΡΠ΅ΠΌ ΡΡΠ°ΠΏΠ°ΠΌ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠ°ΠΊΠΎΠΏΠ»Π΅Π½ΠΈΠ΅ Π Π€Π Π² ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Β ΠΎΡΠ°Π³Π°Ρ
Π² ΠΏΠΎΠ΄Π°Π²Π»ΡΡΡΠ΅ΠΌ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π΅ ΡΠ»ΡΡΠ°Π΅Π² (98%)Β Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΎΠ²Π°Π»ΠΎΡΡ Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠΈΠΌΠΈ Π·Π½Π°ΡΠ΅Π½ΠΈΡΠΌΠΈΒ maxSUV1,2,3 ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π½Π΅ΠΏΠΎΡΠ°ΠΆΠ΅Π½Π½ΠΎΠ³ΠΎ Π²Π΅ΡΠ΅ΡΡΠ²Π°Β Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π° ΠΈ ΡΠΎΠ»ΡΠΊΠΎ Π² ΠΎΠ΄Π½ΠΎΠΌ ΡΠ»ΡΡΠ°Π΅ Π½Π°ΠΊΠΎΠΏΠ»Π΅Π½ΠΈΠ΅ Π½Π΅Β ΠΏΡΠ΅Π²ΡΡΠ°Π»ΠΎ ΡΠΎΠ½ΠΎΠ²ΠΎΠ΅. Π‘ΡΠ΅Π΄Π½ΠΈΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΡ TBR1,2,3 Π±ΡΠ»ΠΈΒ Π²ΡΡΠ΅ ΠΏΡΠΈ ΡΠ΅ΡΠΈΠ΄ΠΈΠ²Π°Ρ
ΠΌΠ΅ΡΠ°ΡΡΠ°Π·ΠΎΠ², ΡΠ΅ΠΌ ΠΏΡΠΈ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡΡ
Β ΡΠΌΠ΅ΡΠ°Π½Π½ΠΎΠ³ΠΎ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ° ΠΈ Π»ΡΡΠ΅Π²ΠΎΠΌ Π½Π΅ΠΊΡΠΎΠ·Π΅. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π°Β Π·Π½Π°ΡΠΈΠΌΠΎΡΡΡ ΠΏΠ΅ΡΠ²ΠΎΠ³ΠΎ ΡΡΠ°ΠΏΠ° ΡΠΊΠ°Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Ρ Π²ΡΡΠΈΡΠ»Π΅Π½ΠΈΠ΅ΠΌΒ TBR1 β ΠΏΡΠΈ ΡΠ΅ΡΠΈΠ΄ΠΈΠ²Π΅ Π·Π½Π°ΡΠ΅Π½ΠΈΡ ΠΏΡΠ΅Π²ΡΡΠ°Π»ΠΈ 2,0, ΠΏΡΠΈ ΡΠΌΠ΅ΡΠ°Π½Π½ΡΡ
ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡΡ
ΠΈ Π½Π΅ΠΊΡΠΎΠ·Π΅ Π·Π½Π°ΡΠ΅Π½ΠΈΡ Π±ΡΠ»ΠΈ Π½ΠΈΠΆΠ΅ 2,0.Β ΠΠΎΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΡΡ ΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΡ Π΄Π°Π΅Ρ Π³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΠΈ TBR1,2,3, ΠΊΠΎΡΠΎΡΡΠΉ ΡΠ°ΠΊΠΆΠ΅ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²Π°ΡΡ ΡΠΌΠ΅ΡΠ°Π½Π½ΡΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΠΈ ΠΏΠΎΡΡΠ»ΡΡΠ΅Π²ΠΎΠΉΒ Π½Π΅ΠΊΡΠΎΠ· ΠΏΠΎ Π²Π΅ΠΊΡΠΎΡΡ ΠΊΡΠΈΠ²ΠΎΠΉ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· Π·Π½Π°ΡΠ΅Π½ΠΈΡ TBR1Β ΠΈ ΡΠΈΠΏΠ° ΠΊΡΠΈΠ²ΠΎΠΉ ΡΠ²Π»ΡΠ΅ΡΡΡ Π±ΠΎΠ»Π΅Π΅ ΡΠΎΡΠ½ΡΠΌ ΠΊΡΠΈΡΠ΅ΡΠΈΠ΅ΠΌ, ΡΠ΅ΠΌΒ ΠΎΠ΄ΠΈΠ½ΠΎΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· maxSUV1,2,3 Π² ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΌ ΡΡΠ°ΡΡΠΊΠ΅. Π ΡΠ»ΡΡΠ°Π΅ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΡΠ΅ΡΠΈΠ΄ΠΈΠ²Π° Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ Π°ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΡΡΠ°ΡΡΠΊΠ°, ΡΡΠΎ ΠΈΠ³ΡΠ°Π΅Ρ Π²Π°ΠΆΠ½ΡΡΒ ΡΠΎΠ»Ρ ΠΏΡΠΈ ΠΏΠ»Π°Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΏΠΎΠ²ΡΠΎΡΠ½ΠΎΠΉ Π‘Π Π₯.Β ΠΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΡΠΌΠ΅ΡΠ°Π½Π½ΠΎΠ³ΠΎ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ° ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ ΠΈΠΌΠ΅Π΅ΡΒ ΠΏΡΠΎΠ³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Ρ
Π°ΡΠ°ΠΊΡΠ΅Ρ ΠΈ Π² Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π΅ ΡΠ»ΡΡΠ°Π΅Π²Β ΠΏΠΎΠ΄ΡΠ°Π·ΡΠΌΠ΅Π²Π°Π΅Ρ Π΄ΠΈΠ½Π°ΠΌΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ