22 research outputs found
ΠΠΌΠΌΡΠ½ΠΎΠ»ΠΎΠ³ΠΈΡ ΠΈ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Ρ ΠΈΠΌΠΌΡΠ½ΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ Π³Π»ΠΈΠΎΠΌ: ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ°ΠΊΡΠΎΡΠΎΠ² Π³ΡΠΌΠΎΡΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΈΠΌΠΌΡΠ½ΠΈΡΠ΅ΡΠ°
High-grade gliomas are aggressive brain tumors with limited survival rates. To date the maximum of survival benefit of conventional therapeutic options has been already reached and innovative treatment strategies, based on tumor biology are urgently needed. Generally, malignant gliomas, including glioblastoma, are immunologically βcold: neoplasms, with weak anti-tumor immune response and peritumoral inflammation, caused by reduced expression of neoantigens by tumor cells and restricted immunoreactivity of the microenvironment. The reduced immunogenicity of brain structures is conditioned by the absence of homing molecules for white blood cells on them, as well as the suppression of activated (CD178+) T cells by brain gangliosides. The cell population infiltrating malignant glioma is impoverished with cytotoxic T cells (CD8+ FOXP3β) and oppositely enriched with regulatory T cells and type 2 macrophages (M2). An effective anti-glioma immune response is resulted in increasing the total number of tumor-infiltrating lymphocytes and the CD8+ cell content; switching the functional activity of macrophages from M2 to M1 type. Integration of immunotherapeutic technologies (vaccines and monoclonal antibodies) into treatment strategies of malignant gliomas is relevant and promising approach based on biological features of the tumor.ΠΠ»ΠΈΠΎΠΌΡ Π²ΡΡΠΎΠΊΠΎΠΉ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΡΡΠΈ β Π°Π³ΡΠ΅ΡΡΠΈΠ²Π½ΡΠ΅ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ ΡΠ΅Π½ΡΡΠ°Π»ΡΠ½ΠΎΠΉ Π½Π΅ΡΠ²Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ. Π‘ΡΠ°Π½Π΄Π°ΡΡΠ½Π°Ρ Ρ
ΠΈΠΌΠΈΠΎΠ»ΡΡΠ΅Π²Π°Ρ ΡΠ΅ΡΠ°ΠΏΠΈΡ Π΄Π°Π½Π½ΡΡ
Π½ΠΎΠ²ΠΎΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠΉ Π½Π΅ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΊΡΡΠ°ΡΠΈΠ²Π½ΠΎΠΉ ΠΎΠΏΡΠΈΠ΅ΠΉ, ΠΏΠΎΡΡΠΎΠΌΡ ΠΏΠΎΠΏΡΡΠΊΠΈ ΡΡΠΈΠ»Π΅Π½ΠΈΡ ΠΈ ΠΈΠ½Π΄ΠΈΠ²ΠΈΠ΄ΡΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΈΡ
Π»Π΅ΡΠ΅Π½ΠΈΡ Π½Π° ΡΠ΅Π³ΠΎΠ΄Π½ΡΡΠ½ΠΈΠΉ Π΄Π΅Π½Ρ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»Π°Π³Π°ΡΡ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Π½Π° ΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΡ ΡΠΎΡΡΠ° ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ Π½Π° ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΌ ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΌ ΡΡΠΎΠ²Π½ΡΡ
. ΠΠ»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠ΅ Π³Π»ΠΈΠΎΠΌΡ, Π² ΠΏΠ΅ΡΠ²ΡΡ ΠΎΡΠ΅ΡΠ΅Π΄Ρ Π³Π»ΠΈΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ, ΡΠ²Π»ΡΡΡΡΡ Β«Ρ
ΠΎΠ»ΠΎΠ΄Π½ΡΠΌΠΈΒ» ΠΎΠΏΡΡ
ΠΎΠ»ΡΠΌΠΈ, Π² ΠΊΠΎΡΠΎΡΡΡ
ΠΈΠΌΠΌΡΠ½Π½ΡΠΉ ΠΎΡΠ²Π΅Ρ ΠΈ ΠΏΠ΅ΡΠΈΡΡΠΌΠΎΡΠ°Π»ΡΠ½ΠΎΠ΅ Π²ΠΎΡΠΏΠ°Π»Π΅Π½ΠΈΠ΅ ΠΏΡΠΎΡΠ²Π»ΡΡΡΡΡ ΡΠ»Π°Π±ΠΎ. ΠΡΠΎ ΠΎΠ±ΡΡΡΠ½ΡΠ΅ΡΡΡ ΡΠ½ΠΈΠΆΠ΅Π½Π½ΠΎΠΉ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠ΅ΠΉ Π½Π΅ΠΎΠ°Π½ΡΠΈΠ³Π΅Π½ΠΎΠ² ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΠΌΠΈ ΠΊΠ»Π΅ΡΠΊΠ°ΠΌΠΈ ΠΈ Π½ΠΈΠ·ΠΊΠΎΠΉ ΠΈΠΌΠΌΡΠ½ΠΎΡΠ΅Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ ΠΌΠΈΠΊΡΠΎΠΎΠΊΡΡΠΆΠ΅Π½ΠΈΡ. ΠΠ»Π΅ΡΠΊΠΈ ΡΠ΅Π½ΡΡΠ°Π»ΡΠ½ΠΎΠΉ Π½Π΅ΡΠ²Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ Π»ΠΈΡΠ΅Π½Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ» Π΄Π»Ρ Ρ
ΠΎΠΌΠΈΠ½Π³Π° Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠΎΠ², Π° ΠΏΠΎΠ²Π΅ΡΡ
Π½ΠΎΡΡΠ½ΡΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ β Π³Π°Π½Π³Π»ΠΈΠΎΠ·ΠΈΠ΄Ρ β ΠΎΠΊΠ°Π·ΡΠ²Π°ΡΡ ΠΏΡΡΠΌΠΎΠ΅ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΡΡΡΠ΅Π΅ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Π½Π° CD178+-ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Π’-Π»ΠΈΠΌΡΠΎΡΠΈΡΡ. ΠΡΠΎ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΡΠΎΠΌΡ, ΡΡΠΎ ΠΏΠΎΠΏΡΠ»ΡΡΠΈΡ Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠΎΠ², ΠΈΠ½ΡΠΈΠ»ΡΡΡΠΈΡΡΡΡΠΈΡ
ΠΎΠΏΡΡ
ΠΎΠ»Ρ, ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π° Π² ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΌ ΠΊΠ»Π΅ΡΠΊΠ°ΠΌΠΈ, ΠΎΡΡΠΈΡΠ°ΡΠ΅Π»ΡΠ½ΠΎ ΡΠ΅Π³ΡΠ»ΠΈΡΡΡΡΠΈΠΌΠΈ ΠΈΠΌΠΌΡΠ½Π½ΡΠΉ ΠΎΡΠ²Π΅Ρ (ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΠΌΠΈ (CD4+ CD25+ FOXP3+) T-Π»ΠΈΠΌΡΠΎΡΠΈΡΠ°ΠΌΠΈ ΠΈ ΠΌΠ°ΠΊΡΠΎΡΠ°Π³Π°ΠΌΠΈ 2-Π³ΠΎ ΡΠΈΠΏΠ°). ΠΠ°ΠΊΡΠΎΡΠ°Π³ΠΈ 2-Π³ΠΎ ΡΠΈΠΏΠ° ΠΈΠ½Π³ΠΈΠ±ΠΈΡΡΡΡ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΉ ΠΈΠΌΠΌΡΠ½Π½ΡΠΉ ΠΎΡΠ²Π΅Ρ, ΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡ Π½Π΅ΠΎΠ°Π½Π³ΠΈΠΎΠ³Π΅Π½Π΅Π· ΠΈ ΡΠΎΠ·Π΄Π°ΡΡ ΡΡΠ»ΠΎΠ²ΠΈΡ Π΄Π»Ρ ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½ΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ.ΠΠ½ΡΠ΅Π³ΡΠ°ΡΠΈΡ Π² Π»Π΅ΡΠ΅Π½ΠΈΠΈ ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ ΡΠ΅Π½ΡΡΠ°Π»ΡΠ½ΠΎΠΉ Π½Π΅ΡΠ²Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ ΠΈΠΌΠΌΡΠ½ΠΎΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΎΠ², Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π²Π°ΠΊΡΠΈΠ½ ΠΈ ΠΌΠΎΠ½ΠΎΠΊΠ»ΠΎΠ½Π°Π»ΡΠ½ΡΡ
Π°Π½ΡΠΈΡΠ΅Π», ΡΠ²Π»ΡΠ΅ΡΡΡ Π°ΠΊΡΡΠ°Π»ΡΠ½ΠΎΠΉ ΡΡΡΠ°ΡΠ΅Π³ΠΈΠ΅ΠΉ, ΠΎΡΠ½ΠΎΠ²Π°Π½Π½ΠΎΠΉ Π½Π° Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ²ΠΎΠΉΡΡΠ²Π°Ρ
ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ
ΠΠ½Π°Π»ΠΈΠ· Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ Π°Π±Π΅ΡΡΠ°ΡΠΈΠΉ Π² Π³Π»ΠΈΠΎΠΌΠ°Ρ Π²ΡΡΠΎΠΊΠΎΠΉ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΡΡΠΈ Ρ Π΄Π΅ΡΠ΅ΠΉ
Background. High-grade gliomas are characterized by a wide range of genetic abnormalities. The heterogeneous genomic landscape of pediatric high-grade gliomas allows identifying distinct subgroups of the disease in children and young adults. Most importantly, these subgroups differ by clinical course and prognosis, as well as treatment response to standard therapy.Objective: to assess the profile of molecular genetic markers of high-grade gliomas in children.Materials and methods. In the current study, we examine the frequency of H3F3A, Hist1H3B, BRAF, IDH1 / 2 mutations, the copy number alterations of CDKN2A / 2B genes and the expression of ETV6βNTRK3 fusion gene in a cohort of 53 pediatric high-grade gliomas.Results. Driver mutations and CDKN2A / 2B deletions were observed in 24 (45 %) and 15 (28 %) of 53 tumors, respectively. Overall, the studied high-grade gliomas harbored 41 genetic aberrations including 24 (58.5 %) somatic missense mutations, 1 (2.4 %) genetic variant of unknown clinical significance, 1 (2.4 %) oncogenic fusion gene and 15 (36.6 %) deletions of the tumor suppressor genes.Conclusion. These findings point to the importance of molecular profiling of tumors for the optimal clinical care and development of new approaches to treatment aimed at molecular targets for personalized anticancer therapies.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠΡΡΠΎΠΊΠΎΠ·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠ΅ Π³Π»ΠΈΠΎΠΌΡ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΡΡΡΡ ΡΠΈΡΠΎΠΊΠΈΠΌ ΡΠΏΠ΅ΠΊΡΡΠΎΠΌ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΉ. Π Π°Π·Π»ΠΈΡΠΈΡ Π² ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΌ ΠΏΡΠΎΡΠΈΠ»Π΅ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡ Π²ΡΠ΄Π΅Π»ΠΈΡΡ Π½Π΅ΡΠΊΠΎΠ»ΡΠΊΠΎ ΠΎΡΠ½ΠΎΠ²Π½ΡΡ
ΠΏΠΎΠ΄Π³ΡΡΠΏΠΏ Π³Π»ΠΈΠΎΠΌ Π²ΡΡΠΎΠΊΠΎΠΉ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΡΡΠΈ Ρ Π΄Π΅ΡΠ΅ΠΉ ΠΈ ΠΏΠΎΠ΄ΡΠΎΡΡΠΊΠΎΠ², ΠΊΠΎΡΠΎΡΡΠ΅ ΡΠ°Π·Π»ΠΈΡΠ°ΡΡΡΡ ΠΊΠ°ΠΊ ΠΏΠΎ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΌΡ ΡΠ΅ΡΠ΅Π½ΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ, Π΅Π³ΠΎ ΠΏΡΠΎΠ³Π½ΠΎΠ·Ρ, ΡΠ°ΠΊ ΠΈ ΠΏΠΎ ΠΎΡΠ²Π΅ΡΡ Π½Π° ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΡΠ΅ ΡΡ
Π΅ΠΌΡ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΎΡΠ΅Π½ΠΈΡΡ ΠΏΡΠΎΡΠΈΠ»Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² Π³Π»ΠΈΠΎΠΌ Π²ΡΡΠΎΠΊΠΎΠΉ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΡΡΠΈ Ρ Π΄Π΅ΡΠ΅ΠΉ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. Π ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π±ΡΠ»ΠΈ Π²ΠΊΠ»ΡΡΠ΅Π½Ρ 53 ΠΎΠ±ΡΠ°Π·ΡΠ° Π³Π»ΠΈΠΎΠΌ Π²ΡΡΠΎΠΊΠΎΠΉ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΡΡΠΈ Ρ Π΄Π΅ΡΠ΅ΠΉ. ΠΡΠ»ΠΈ ΠΏΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Ρ ΠΌΡΡΠ°ΡΠΈΠΈ Π² Π³Π΅Π½Π°Ρ
H3F3A, Hist1H3B, BRAF, IDH1/2, Π° ΡΠ°ΠΊΠΆΠ΅ Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΈ ΡΠΈΡΠ»Π° ΠΊΠΎΠΏΠΈΠΉ Π³Π΅Π½ΠΎΠ² CDKN2A/2B ΠΈ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ Ρ
ΠΈΠΌΠ΅ΡΠ½ΠΎΠ³ΠΎ Π³Π΅Π½Π° ETV6βNTRK3.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π 24 (45 %) ΠΈΠ· 53 ΠΏΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΠ»ΡΡΠ°Π΅Π² Π²ΡΡΠ²Π»Π΅Π½Π° Π΄ΡΠ°ΠΉΠ²Π΅ΡΠ½Π°Ρ ΠΌΡΡΠ°ΡΠΈΡ Π² ΡΠΊΠ°Π½ΠΈ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ, Π² 15 (28 %) β ΠΏΠΎΡΠ΅ΡΡ ΠΊΠΎΠΏΠΈΠΈ CDKN2A / 2B, ΠΊΠΎΡΠΎΡΠ°Ρ ΠΌΠΎΠΆΠ΅Ρ Π²ΡΡΡΡΠΏΠ°ΡΡ ΠΊΠ°ΠΊ Π²ΡΠΎΡΠΎΠ΅ ΠΌΡΡΠ°ΡΠΈΠΎΠ½Π½ΠΎΠ΅ ΡΠΎΠ±ΡΡΠΈΠ΅. Π ΠΎΠ±ΡΠ΅ΠΉ ΡΠ»ΠΎΠΆΠ½ΠΎΡΡΠΈ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Π° 41 Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠ°Ρ Π°Π±Π΅ΡΡΠ°ΡΠΈΡ, ΠΈΠ· Π½ΠΈΡ
24 (58,5 %) ΡΠΎΡΡΠ°Π²Π»ΡΡΡ ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠΈΡΡΠ΅Π½Ρ-ΠΌΡΡΠ°ΡΠΈΠΈ, 1 (2,4 %) β Π²Π°ΡΠΈΠ°Π½Ρ Ρ Π½Π΅ΡΡΠ½ΡΠΌ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ΠΌ, 1 (2,4 %) β Ρ
ΠΈΠΌΠ΅ΡΠ½ΡΠΉ ΠΎΠ½ΠΊΠΎΠ³Π΅Π½ ΠΈ 15 (36,6 %) β Π΄Π΅Π»Π΅ΡΠΈΠΈ Π³Π΅Π½ΠΎΠ²-ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠΎΠ².ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ Π΄Π°Π½Π½ΡΠ΅ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎ Π²Π°ΠΆΠ½ΠΎΡΡΠΈ ΡΠ³Π»ΡΠ±Π»Π΅Π½Π½ΠΎΠ³ΠΎ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΡΠΈΠ»Ρ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ Π΄Π»Ρ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΡΠ°ΠΊΡΠΈΠΊΠΈ Π²Π΅Π΄Π΅Π½ΠΈΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΠΎΠ΄Π±ΠΎΡΠ° ΠΏΠ΅ΡΡΠΎΠ½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π΄Π»Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠΌΠΈ Π³Π»ΠΈΠΎΠΌΠ°ΠΌΠΈ
Transluminal angioplasty in postsurgical stenosis of the extracranial carotid artery.
Transluminal angioplasty of the common carotid artery was beneficial in a patient with postendarterectomy recurrent stenosis due to fibrous myointimal hyperplasia. This lesion is the major cause of restenosis within the first 24 postoperative months and has histologic characteristics quite favorable for angioplasty with minimal possibility for embolic complications. Since surgery is a proven procedure with low morbidity/mortality for most patients, the authors believe transluminal angioplasty for carotid restenosis should be limited to surgically inaccessible lesions or patients presenting unacceptable operative risk, as in the case described
Arteriovenous fistula simulating arteriovenous malformation.
A 36-year-old man was thought (for 20 years) to have an arteriovenous malformation that could not be excised. Repeated ligations of proximal arterial supply to the vascular lesion were only transiently beneficial and may have caused a delay in correct diagnosis because of impaired angioaccess. Once it was discovered that he had an arteriovenous fistula--probably caused by a tonsillectomy at age 6--it was possible to occlude the fistula with detachable balloons. The mass and his headaches subsequently resolved. AV fistulas are caused by trauma. Growth of AVMs is often stimulated by trauma. Both lesions have pulsatile masses associated with overlying bruits. The differential diagnosis can usually be made by arteriography, since AV fistulas are acquired lesions with a single communication between an artery and a vein, whereas AVMs are congenital lesions with multiple, large arterial feeding vessels and numerous arteriovenous communications. Proper diagnosis is important, since AVMs are aggressive lesions that tend to regrow if not completely excised. AV fistulas will be cured if the single arteriovenous communication can be obliterated. Proper treatment for AV fistula is obliteration of the single arteriovenous communication, operatively or with occlusive balloons; treatment of AVMs--when possible--is excision of the entire mass, combined (on occasion) with preoperative embolization of the tumor mass. This case report emphasizes the importance of accuracy in the differential diagnosis between arteriovenous malformations and arteriovenous fistulas; moreover, it demonstrates both the ineffectiveness and deleterious consequences of proximal arterial ligation, since collateral development is enhanced and angiographic access is compromised
Suppressed miR-128-3p combined with TERT overexpression predicts dismal outcomes for neuroblastoma
BACKGROUND: Molecular and clinical diversity of neuroblastomas is notorious. The activating TERT rearrangements have been associated with dismal prognosis. Suppression of miR-128-3p may complement and enhance the adverse effects of TERT overexpression. OBJECTIVE: The study aimed at evaluation of prognostic significance of the miR-128-3p/TERT expression in patients with primary neuroblastoma. METHODS: RNA samples isolated from fresh-frozen tumor specimens (n= 103) were reverse transcribed for evaluation of miR-128-3p and TERT expression by qPCR. The normalized expression levels were tested for correlations with the event-free survival (EFS). ROC-analysis was used to establish threshold expression levels (TLs) for the possible best prediction of the outcomes. The median follow-up was 57 months. RESULTS: Both TERT overexpression and miR-128-3p downregulation were independently associated with superior rates of adverse events (p= 0.027, TL =-2.32 log10 and p= 0.080, TL =-1.33 log10, respectively). The MYCN single-copy patients were stratified into groups based on the character of alterations in expression of the studied transcripts. Five-year EFS in the groups of patients with elevated TERT/normal miR-128-3p expression and normal TERT/reduced miR-128-3p expression were 0.74 Β± 0.08 and 0.60 Β± 0.16, respectively. The patients with elevated TERT/reduced miR-128-3p expression had the worst outcomes, with 5-year EFS of 0.40 Β± 0.16 compared with 0.91 Β± 0.06 for the patients with unaltered levels of both transcripts (p< 0.001). Cumulative incidence of relapse/progression for the groups constituted 0.23 Β± 0.08, 0.40 Β± 0.16, 0.60 Β± 0.16 and 0.09 Β± 0.06, respectively. Moreover, the loss of miR-128-3p was qualified as independent adverse predictor which outperformed the conventional clinical and genetic risk factors in the multivariate Cox regression model of EFS. CONCLUSIONS: Combined expression levels of miR-128-3p and TERT represent a novel prognostic biomarker for neuroblastoma
Congenital medulloblastoma: Fetal and postnatal longitudinal observation with quantitative MRI
Congenital medulloblastoma is extremely rare. MRI appearance of this tumor in the fetal brain has not been described. A case of congenital medulloblastoma initially observed by antenatal MRI with postnatal follow-up and treatment is presented. A pregnant female underwent fetal MRI on the 31st gestational week for routine indications. Midline cerebellar lesion of β€2β―cm in size with minor T2 hypointensity and T1 hyperintensity was identified. Additionally, quantitative MRI including apparent diffusion coefficient (ADC) and fast macromolecular proton fraction (MPF) mapping was performed. The lesion showed a marked ADC decrease and MPF increase. MPF maps depicted the lesion most conspicuously. After term delivery, a male neonate presented with symptoms of increased intracranial pressure. Postnatal MRI identified obstructive hydrocephalus caused by a large posterior fossa mass. The child was treated by cerebrospinal fluid shunt placement. Follow-up quantitative MRI on the fifth month revealed tumor growth and vivid changes of its tissue contrast associated with brain maturation. The tumor appeared nearly isointense on T1- and T2-weighted images and slightly hypointense on the ADC map. MPF contrast showed the most remarkable change from hyper- to hypointensity due to brain myelination with stable MPF in the tumor. Subsequently, the child underwent partial tumor resection, and currently continues treatment with chemotherapy. The pathological diagnosis was desmoplastic/nodular medulloblastoma. The described case illustrates evolution of the tumor contrast in the course of fetal and postnatal brain development and highlights the added diagnostic value of MPF mapping in fetal and neonatal neuroimaging
Analysis of genetic aberrations in pediatric high-grade gliomas
Background. High-grade gliomas are characterized by a wide range of genetic abnormalities. The heterogeneous genomic landscape of pediatric high-grade gliomas allows identifying distinct subgroups of the disease in children and young adults. Most importantly, these subgroups differ by clinical course and prognosis, as well as treatment response to standard therapy.Objective: to assess the profile of molecular genetic markers of high-grade gliomas in children.Materials and methods. In the current study, we examine the frequency of H3F3A, Hist1H3B, BRAF, IDH1 / 2 mutations, the copy number alterations of CDKN2A / 2B genes and the expression of ETV6βNTRK3 fusion gene in a cohort of 53 pediatric high-grade gliomas.Results. Driver mutations and CDKN2A / 2B deletions were observed in 24 (45 %) and 15 (28 %) of 53 tumors, respectively. Overall, the studied high-grade gliomas harbored 41 genetic aberrations including 24 (58.5 %) somatic missense mutations, 1 (2.4 %) genetic variant of unknown clinical significance, 1 (2.4 %) oncogenic fusion gene and 15 (36.6 %) deletions of the tumor suppressor genes.Conclusion. These findings point to the importance of molecular profiling of tumors for the optimal clinical care and development of new approaches to treatment aimed at molecular targets for personalized anticancer therapies
Congenital medulloblastoma: Fetal and postnatal longitudinal observation with quantitative MRI
Congenital medulloblastoma is extremely rare. MRI appearance of this tumor in the fetal brain has not been described. A case of congenital medulloblastoma initially observed by antenatal MRI with postnatal follow-up and treatment is presented. A pregnant female underwent fetal MRI on the 31st gestational week for routine indications. Midline cerebellar lesion of β€2β―cm in size with minor T2 hypointensity and T1 hyperintensity was identified. Additionally, quantitative MRI including apparent diffusion coefficient (ADC) and fast macromolecular proton fraction (MPF) mapping was performed. The lesion showed a marked ADC decrease and MPF increase. MPF maps depicted the lesion most conspicuously. After term delivery, a male neonate presented with symptoms of increased intracranial pressure. Postnatal MRI identified obstructive hydrocephalus caused by a large posterior fossa mass. The child was treated by cerebrospinal fluid shunt placement. Follow-up quantitative MRI on the fifth month revealed tumor growth and vivid changes of its tissue contrast associated with brain maturation. The tumor appeared nearly isointense on T1- and T2-weighted images and slightly hypointense on the ADC map. MPF contrast showed the most remarkable change from hyper- to hypointensity due to brain myelination with stable MPF in the tumor. Subsequently, the child underwent partial tumor resection, and currently continues treatment with chemotherapy. The pathological diagnosis was desmoplastic/nodular medulloblastoma. The described case illustrates evolution of the tumor contrast in the course of fetal and postnatal brain development and highlights the added diagnostic value of MPF mapping in fetal and neonatal neuroimaging
Prospective investigation of applicability and the prognostic significance of bone marrow involvement in patients with neuroblastoma detected by quantitative reverse transcription PCR
Background: Detection of bone marrow (BM) involvement in patients with neuroblastoma is crucial for staging and defining prognosis. Furthermore, the persistence of residual tumor cells in the BM is associated with an unfavorable outcome. Methods: Expression of PHOX2B, TH, ELAVL4, and B4GALNT1 (GD2-synthase) was analyzed by quantitative polymerase chain reaction in neuroblastoma cell lines, control BM samples, and in BM samples from patients. The threshold level of expression for each gene was established through receiver operator characteristic analysis and used to determine the diagnostic test performance. The prognostic significance of BM involvement was assessed by survival rates calculations. The median of follow-up time was 36.1 months. Results: Neither PHOX2B nor TH expression was detected in control BM, while expression of ELAVL4 was found in 20 (76.9%) and GD2-synthase in 15 (57.7%) of 26 samples. The overall correct predictive value for TH, ELAVL4, and GD2-synthase, based on thresholds levels, was 0.952, 0.828, and 0.767, respectively, whereas the overall correct predictive value for PHOX2B was 0.994. The PHOX2B/TH expression in diagnostic BM of patients with neuroblastoma corresponded with a decreased survival rate (PΒ Β 1.68 in the diagnostic BM samples demonstrated an adverse prognostic effect (PΒ =Β 0.006). Persistence of PHOX2B/TH expression in the BM during and after induction chemotherapy resulted in dismal outcome (PΒ =Β 0.022 and PΒ =Β 0.012). Conclusion: PHOX2B and TH are the most optimal markers for detection of BM involvement, allowing identification of high-risk patients. Predominance of PHOX2B expression over TH has a strong adverse prognostic impact