9 research outputs found
The Formation and Development Trends of the Consulting Market in Russia
In the conditions of rapid growth of service industries and, above all, business services, the importance of advisory services (consulting) is steadily enhancing for the domestic economy and the growth of its competitiveness. The article analyzes the basic processes occurring in the modern Russian market of consulting services, the trends and patterns of its development, including the growing processes of concentration and centralization, the underdevelopment of market institutions, the lack of legislation regulating this market segment, structural defects associated with the excessive income growth of the management consulting. All this allowed us to draw some important conclusions about the unstable and contradictory nature of the development of the domestic market of consulting, the deformation of its structure and the absence of the state policy in the sphere of regulation of the consulting services market, and to develop recommendations for its stabilization, including the improvement of legislation in the field of intellectual property, the expansion and strengthening of the foreign economic positions of the consulting companies in Russia, the efficiency improvement of their participation in the international division of labor. The article is intended for students studying methods of conducting marketing research on the market of consulting services, teachers of the discipline "Marketing in services", "Consulting" as well as for marketing managers and managers of consulting companies elaborating strategies for their development.
DOI: 10.5901/mjss.2015.v6n2s3p18
Π¦ΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ½ΡΠ΅ ΠΊΠ°ΡΠΈΠΎΠ½Π½ΡΠ΅ ΠΏΠ΅ΠΏΡΠΈΠ΄Ρ ΠΊΠ°ΠΊ Π»ΠΈΠ³Π°Π½Π΄Ρ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΠΎΠ³ΠΎ Π½ΡΠΊΠ»Π΅ΠΎΠ»ΠΈΠ½Π°
Background. Chaperone proteins nucleolin (NCL, or C23) and nucleophosmin (NPM, or B23) regulate key cell functions. The most tumors are characterized by over-expression of these proteins, especially in cell nuclei and on the Ρell surface, as NCL. Differential expression of NCL/NPM in tumor and normal cells is the basis of selective cytotoxicity of cationic peptides β expected ligands for these proteins. Objective. Analysis of the interactions between nucleolin and some peptides with high nonspecific toxicity for tumor cells. Materials and methods. The interaction of 4 previously characterized cationic peptides with nucleolin dimer was analyzed by pair molecular docking using Maestro 11 program. Results and conclusion. It is shown that these peptides can associate with receptor nucleolin molecules, forming energy-stable complexes. In the active centre of NCL molecule were found, at least, 7 positions of amino acids, which bind to the tested peptides at a high frequency (43β100 %). This indicates the conservative structure of dimer NCL, its stable binding to peptide ligands and the possibility of design the optimal structure of cationic peptides that induce tumor cell death due to competing binding to the target proteins.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. Π¨Π°ΠΏΠ΅ΡΠΎΠ½Π½ΡΠ΅ Π±Π΅Π»ΠΊΠΈ Π½ΡΠΊΠ»Π΅ΠΎΠ»ΠΈΠ½ (NCL, ΠΈΠ»ΠΈ Π‘23) ΠΈ Π½ΡΠΊΠ»Π΅ΠΎΡΠΎΠ·ΠΌΠΈΠ½ (NPM, ΠΈΠ»ΠΈ Π23) ΡΠ΅Π³ΡΠ»ΠΈΡΡΡΡ ΠΊΠ»ΡΡΠ΅Π²ΡΠ΅ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠ΅ ΡΡΠ½ΠΊΡΠΈΠΈ. ΠΠ»Ρ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π° ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ½Π° Π³ΠΈΠΏΠ΅ΡΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΡΠΈΡ
Π±Π΅Π»ΠΊΠΎΠ², ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎ Π² ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
ΡΠ΄ΡΠ°Ρ
, Π° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΠΎΠ³ΠΎ NCL β ΡΠ°ΠΊΠΆΠ΅ ΠΈ Π½Π° ΠΏΠΎΠ²Π΅ΡΡ
Π½ΠΎΡΡΠΈ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ. ΠΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½Π°Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ NCL/NPM Π² ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΈ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΡΡ
ΠΊΠ»Π΅ΡΠΊΠ°Ρ
ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»ΠΈΠ²Π°Π΅Ρ ΠΈΠ·Π±ΠΈΡΠ°ΡΠ΅Π»ΡΠ½ΡΡ ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΡ ΠΊΠ°ΡΠΈΠΎΠ½Π½ΡΡ
ΠΏΠ΅ΠΏΡΠΈΠ΄ΠΎΠ² β ΠΏΡΠ΅Π΄ΠΏΠΎΠ»Π°Π³Π°Π΅ΠΌΡΡ
Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² ΡΡΠΈΡ
Π±Π΅Π»ΠΊΠΎΠ². Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β Π°Π½Π°Π»ΠΈΠ· Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠΉ ΠΌΠ΅ΠΆΠ΄Ρ Π½ΡΠΊΠ»Π΅ΠΎΠ»ΠΈΠ½ΠΎΠΌ ΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΠΌΠΈ ΠΏΠ΅ΠΏΡΠΈΠ΄Π°ΠΌΠΈ, ΠΎΠ±Π»Π°Π΄Π°ΡΡΠΈΠΌΠΈ Π²ΡΡΠΎΠΊΠΎΠΉ ΠΈΠ·Π±ΠΈΡΠ°ΡΠ΅Π»ΡΠ½ΠΎΠΉ ΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΡΡ Π² ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠΈ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ. ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΡΠ΅ΠΌ ΠΏΠ°ΡΠ½ΠΎΠ³ΠΎ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠ³ΠΎ Π΄ΠΎΠΊΠΈΠ½Π³Π° Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌΡ Maestro 11 ΠΏΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½ΠΎ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ 4 ΡΠ°Π½Π΅Π΅ ΠΎΡ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΎΠ²Π°Π½Π½ΡΡ
ΠΊΠ°ΡΠΈΠΎΠ½Π½ΡΡ
ΠΏΠ΅ΠΏΡΠΈΠ΄ΠΎΠ² Ρ Π΄ΠΈΠΌΠ΅ΡΠΎΠΌ Π½ΡΠΊΠ»Π΅ΠΎΠ»ΠΈΠ½Π°. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈ Π·Π°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΡΡΠΈ ΠΏΠ΅ΠΏΡΠΈΠ΄Ρ ΠΌΠΎΠ³ΡΡ Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°ΡΡ Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ»Π°ΠΌΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΠΎΠ³ΠΎ Π½ΡΠΊΠ»Π΅ΠΎΠ»ΠΈΠ½Π° Π·Π° ΡΡΠ΅Ρ ΡΡΠ°Π±ΠΈΠ»ΡΠ½ΡΡ
Π²ΠΎΠ΄ΠΎΡΠΎΠ΄Π½ΡΡ
ΡΠ²ΡΠ·Π΅ΠΉ, ΠΎΠ±ΡΠ°Π·ΡΡ ΡΠ½Π΅ΡΠ³Π΅ΡΠΈΡΠ΅ΡΠΊΠΈ ΡΡΡΠΎΠΉΡΠΈΠ²ΡΠ΅ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΡ. Π Π°ΠΊΡΠΈΠ²Π½ΠΎΠΌ ΡΠ΅Π½ΡΡΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΠΎΠ³ΠΎ NCL ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΎ Π½Π΅ ΠΌΠ΅Π½Π΅Π΅ 7 Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡΠ½ΡΡ
ΡΠ°ΠΉΡΠΎΠ², ΠΊΠΎΡΠΎΡΡΠ΅ Ρ Π²ΡΡΠΎΠΊΠΎΠΉ ΡΠ°ΡΡΠΎΡΠΎΠΉ (43β100 %) ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΡΡ Ρ ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌΠΈ ΠΏΠ΅ΠΏΡΠΈΠ΄Π°ΠΌΠΈ. ΠΡΠΎ ΡΠΊΠ°Π·ΡΠ²Π°Π΅Ρ Π½Π° ΠΊΠΎΠ½ΡΠ΅ΡΠ²Π°ΡΠΈΠ²Π½ΠΎΡΡΡ ΡΡΡΡΠΊΡΡΡΡ Π΄ΠΈΠΌΠ΅ΡΠ½ΠΎΠ³ΠΎ NCL, ΡΡΠ°Π±ΠΈΠ»ΡΠ½ΠΎΠ΅ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ Π΅Π³ΠΎ Ρ ΠΏΠ΅ΠΏΡΠΈΠ΄Π½ΡΠΌΠΈ Π»ΠΈΠ³Π°Π½Π΄Π°ΠΌΠΈ ΠΈ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΠΈΠ½ΡΠ΅Π·Π° ΠΎΠΏΡΠΈΠΌΠ°Π»ΡΠ½ΡΡ
ΠΏΠΎ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠΉ ΡΡΡΡΠΊΡΡΡΠ΅ ΠΊΠ°ΡΠΈΠΎΠ½Π½ΡΡ
ΠΏΠ΅ΠΏΡΠΈΠ΄ΠΎΠ², ΠΈΠ½Π΄ΡΡΠΈΡΡΡΡΠΈΡ
Π³ΠΈΠ±Π΅Π»Ρ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ Π·Π° ΡΡΠ΅Ρ ΠΊΠΎΠ½ΠΊΡΡΠΈΡΡΡΡΠ΅Π³ΠΎ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ Ρ Π±Π΅Π»ΠΊΠ°ΠΌΠΈ-ΠΌΠΈΡΠ΅Π½ΡΠΌΠΈ.
ΠΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠ°Ρ Π³Π΅ΡΠ΅ΡΠΎΠ³Π΅Π½Π½ΠΎΡΡΡ ΠΌΠ΅Π»Π°Π½ΠΎΠΌΡ Π³Π»Π°Π·Π°
Background. Ocular melanoma is the most common cancer of adult eye and is represented by two main subtypes of uveal (UM) and conjunctival (CM) melanoma with distinct clinical (frequency, localization, histology) and genomic features. The objective is to compare molecular and genetic characteristics of tumors in patients with melanoma of the eye. Materials and methods. In this study molecular profiling of 78 tumors including 73 UM (choroidea, ciliar body and iris) and 5 Π‘M, was evaluated. DNA was isolated from tumor cells collected by macrodissection of FEPE sections of tumor biopsies using proteinase K. The following genes were studied by Sanger sequencing: GNAQ, GNA11, KIT, BRAF, NRAS. Results. Mutations in GNAQ and GNA11 were found in 81 % (59/73) of UM, in 42 % (31/73) and 38 % (28/73) of cases correspondently. GNAQ mutations were more frequent in primary UM (63 %), while GNA11 mutations dominated in metastatic UM (42 %). There was Π° correlation between frequency of GNAQ/GNA11 mutations and histologic type of UM. GNAQ mutations were identified in 55 % of spindle cell UM, while GNA11 mutations were more frequent in epithelioid cell UM (42 %). There were no differences in frequency of GNAQ/GNA11 mutations in UM of patients of different age (younger and elder 50 years). There was no statistically difference in UM patient outcome with GNAQ or GNA11 mutations. We also detected 3 UM with KIT mutations and 2 UM with BRAF mutations. There was no big difference in frequency of Β«driver mutationsΒ» in UM of choroidea, ciliar body and iris. Molecular profiling of conjunctival melanoma (CM) resembles that of cutaneous melanoma of skin: in 3 (60 %) CM BRAF V600E was identified and in 1 (20 %) β NRAS Q61K. Conclusion. Genetic analysis reveals wide diversity of melanoma of eye and is important for it characterization and treatment.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠΠ΅Π»Π°Π½ΠΎΠΌΠ° ΡΠ²Π»ΡΠ΅ΡΡΡ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΠΎΠΉ ΠΎΠΏΡΡ
ΠΎΠ»ΡΡ Π³Π»Π°Π·Π° Ρ Π²Π·ΡΠΎΡΠ»ΡΡ
ΠΈ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π° 2 ΠΎΡΠ½ΠΎΠ²Π½ΡΠΌΠΈ ΡΠΈΠΏΠ°ΠΌΠΈ: ΡΠ²Π΅Π°Π»ΡΠ½ΠΎΠΉ (Π£Π) ΠΈ ΠΊΠΎΠ½ΡΡΠ½ΠΊΡΠΈΠ²Π°Π»ΡΠ½ΠΎΠΉ (ΠΠ), ΠΊΠΎΡΠΎΡΡΠ΅ ΠΎΡΠ»ΠΈΡΠ°ΡΡΡΡ ΠΏΠΎ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌ (ΡΠ°ΡΡΠΎΡΠ° ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½ΠΈΡ, Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΡ, Π³ΠΈΡΡΠΎΠ»ΠΎΠ³ΠΈΡ) ΠΈ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΌ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠ°ΠΌ. Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠ΅ΠΉ ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΌΠ΅Π»Π°Π½ΠΎΠΌΠΎΠΉ Π³Π»Π°Π·Π°. ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. Π‘ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΌΠ΅ΡΠΎΠ΄Π° ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎ Π‘ΡΠ½Π³Π΅ΡΡ Π΄Π»Ρ Π°Π½Π°Π»ΠΈΠ·Π° ΠΠΠ, Π²ΡΠ΄Π΅Π»Π΅Π½Π½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅ ΠΌΠΈΠΊΡΠΎΠ΄ΠΈΡΡΠ΅ΠΊΡΠΈΠΈ ΡΡΠ΅Π·ΠΎΠ² ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
Π±ΠΈΠΎΠΏΡΠΈΠΉ, ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΎ ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΡΠΈΠ»Ρ 78 ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ Π³Π»Π°Π·Π°, ΡΡΠ΅Π΄ΠΈ Π½ΠΈΡ
73 Π£Π (Ρ
ΠΎΡΠΈΠΎΠΈΠ΄Π΅ΠΈ, ΡΠΈΠ»ΠΈΠ°ΡΠ½ΠΎΠ³ΠΎ ΡΠ΅Π»Π° ΠΈ ΡΠ°Π΄ΡΠΆΠΊΠΈ) ΠΈ 5 ΠΠ. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ ΡΠ»Π΅Π΄ΡΡΡΠΈΠΉ ΡΠΏΠ΅ΠΊΡΡ ΠΌΡΡΠ°ΡΠΈΠΉ: GNAQ, GNA11, KIT, BRAF, NRAS. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΡΠ°ΡΠΈΠΈ GNAQ ΠΈ GNA11 Π²ΡΡΠ²Π»Π΅Π½Ρ Π² 81 % (59/73) Π£Π, ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ Π² 42 % (31/73) ΠΈ 38 % (28/73). Π ΠΏΠ΅ΡΠ²ΠΈΡΠ½ΠΎΠΉ Π£Π ΡΠ°ΡΠ΅ ΠΏΡΠΈΡΡΡΡΡΠ²ΠΎΠ²Π°Π»ΠΈ ΠΌΡΡΠ°ΡΠΈΠΈ GNAQ (63 %), Π° Π² ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ β GNA11 (42 %). ΠΠ°Π±Π»ΡΠ΄Π°Π»ΠΈΡΡ ΡΠ°Π·Π»ΠΈΡΠΈΡ Π² ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΠΎΡΡΠΈ ΠΌΡΡΠ°ΡΠΈΠΉ GNAQ ΠΈ GNA11 Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΡΠΈΠΏΠ° ΠΊΠ»Π΅ΡΠΎΠΊ Π£Π. ΠΡΡΠ°ΡΠΈΠΈ GNAQ ΡΠ°ΡΠ΅ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Ρ Π² Π²Π΅ΡΠ΅ΡΠ΅Π½ΠΎΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
Π£Π (55 %), Π° GNA11 β Π² ΡΠΏΠΈΡΠ΅Π»ΠΈΠΎΠΈΠ΄Π½ΡΡ
Π£Π (42 %). ΠΠ΅ Π²ΡΡΠ²Π»Π΅Π½ΠΎ ΡΠ°Π·Π»ΠΈΡΠΈΠΉ Π² ΡΠ°ΡΡΠΎΡΠ΅ ΠΌΡΡΠ°ΡΠΈΠΉ GNAQ/GNA11 Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ Π²ΠΎΠ·ΡΠ°ΡΡΠ° ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² (ΠΌΠΎΠ»ΠΎΠΆΠ΅ ΠΈ ΡΡΠ°ΡΡΠ΅ 50 Π»Π΅Ρ), Π° ΡΠ°ΠΊΠΆΠ΅ Π² ΠΎΠ±ΡΠ΅ΠΉ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Π£Π Ρ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ GNAQ ΠΈΠ»ΠΈ GNA11. ΠΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, Π²ΡΡΠ²Π»Π΅Π½Ρ 3 Π£Π Ρ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ KIT ΠΈ 2 Π£Π Ρ ΠΌΡΡΠ°ΡΠΈΠ΅ΠΉ BRAF. Π Π£Π Ρ
ΠΎΡΠΈΠΎΠΈΠ΄Π΅ΠΈ, ΡΠΈΠ»ΠΈΠ°ΡΠ½ΠΎΠ³ΠΎ ΡΠ΅Π»Π° ΠΈ ΡΠ°Π΄ΡΠΆΠΊΠΈ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΡΠ°Π·Π»ΠΈΡΠΈΠΉ Π² ΡΠ°ΡΡΠΎΡΠ΅ ΠΌΡΡΠ°ΡΠΈΠΉ ΠΎΠ½ΠΊΠΎΠ³Π΅Π½ΠΎΠ² Π½Π΅ Π½Π°Π±Π»ΡΠ΄Π°Π»ΠΎΡΡ. ΠΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠΉ ΠΏΡΠΎΡΠΈΠ»Ρ ΠΠ ΠΎΡΠ»ΠΈΡΠ°Π΅ΡΡΡ ΠΎΡ ΠΏΡΠΎΡΠΈΠ»Ρ ΠΌΡΡΠ°ΡΠΈΠΉ Π£Π ΠΈ ΡΡ
ΠΎΠ΄Π΅Π½ Ρ ΡΠ°ΠΊΠΎΠ²ΡΠΌ Π΄Π»Ρ ΠΌΠ΅Π»Π°Π½ΠΎΠΌΡ ΠΊΠΎΠΆΠΈ: Π² 3 (60 %) ΠΠ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Π° ΠΌΡΡΠ°ΡΠΈΡ BRAF V600E, Π° Π² 1 (20 %) β NRAS Q61K. ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΠ΅Ρ ΠΎ Π³Π΅ΡΠ΅ΡΠΎΠ³Π΅Π½Π½ΠΎΡΡΠΈ ΠΌΠ΅Π»Π°Π½ΠΎΠΌΡ Π³Π»Π°Π·Π° ΠΈ Π²Π°ΠΆΠ΅Π½ Π΄Π»Ρ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ.
Cytotoxic cationic peptides as Π° ligands for receptor nucleolin
Background. Chaperone proteins nucleolin (NCL, or C23) and nucleophosmin (NPM, or B23) regulate key cell functions. The most tumors are characterized by over-expression of these proteins, especially in cell nuclei and on the Ρell surface, as NCL. Differential expression of NCL/NPM in tumor and normal cells is the basis of selective cytotoxicity of cationic peptides β expected ligands for these proteins. Objective. Analysis of the interactions between nucleolin and some peptides with high nonspecific toxicity for tumor cells. Materials and methods. The interaction of 4 previously characterized cationic peptides with nucleolin dimer was analyzed by pair molecular docking using Maestro 11 program. Results and conclusion. It is shown that these peptides can associate with receptor nucleolin molecules, forming energy-stable complexes. In the active centre of NCL molecule were found, at least, 7 positions of amino acids, which bind to the tested peptides at a high frequency (43β100 %). This indicates the conservative structure of dimer NCL, its stable binding to peptide ligands and the possibility of design the optimal structure of cationic peptides that induce tumor cell death due to competing binding to the target proteins
Molecular and genetic diversity in melanoma of eye
Background. Ocular melanoma is the most common cancer of adult eye and is represented by two main subtypes of uveal (UM) and conjunctival (CM) melanoma with distinct clinical (frequency, localization, histology) and genomic features. The objective is to compare molecular and genetic characteristics of tumors in patients with melanoma of the eye. Materials and methods. In this study molecular profiling of 78 tumors including 73 UM (choroidea, ciliar body and iris) and 5 Π‘M, was evaluated. DNA was isolated from tumor cells collected by macrodissection of FEPE sections of tumor biopsies using proteinase K. The following genes were studied by Sanger sequencing: GNAQ, GNA11, KIT, BRAF, NRAS. Results. Mutations in GNAQ and GNA11 were found in 81 % (59/73) of UM, in 42 % (31/73) and 38 % (28/73) of cases correspondently. GNAQ mutations were more frequent in primary UM (63 %), while GNA11 mutations dominated in metastatic UM (42 %). There was Π° correlation between frequency of GNAQ/GNA11 mutations and histologic type of UM. GNAQ mutations were identified in 55 % of spindle cell UM, while GNA11 mutations were more frequent in epithelioid cell UM (42 %). There were no differences in frequency of GNAQ/GNA11 mutations in UM of patients of different age (younger and elder 50 years). There was no statistically difference in UM patient outcome with GNAQ or GNA11 mutations. We also detected 3 UM with KIT mutations and 2 UM with BRAF mutations. There was no big difference in frequency of Β«driver mutationsΒ» in UM of choroidea, ciliar body and iris. Molecular profiling of conjunctival melanoma (CM) resembles that of cutaneous melanoma of skin: in 3 (60 %) CM BRAF V600E was identified and in 1 (20 %) β NRAS Q61K. Conclusion. Genetic analysis reveals wide diversity of melanoma of eye and is important for it characterization and treatment
ΠΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π»Π΅ΠΏΡΠΈΠ½Π° ΠΈ Π΅Π³ΠΎ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΏΡΠΈ ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΌΠ΅Π»Π°Π½ΠΎΠΌΠ΅ ΠΊΠΎΠΆΠΈ
Leptin is a multifunctional hormone with the activity of cytokines, which regulates critical signaling pathways that can induce cell proliferation, invasion, angiogenesis and tumor growth. Leptin plays an important role in the regulation of metabolism, energy exchange, functions of the neuro-endocrine system, including the pituitary, hypothalamus, adrenals, and immune system functions. Recently, some evidences have been appeared concerning the role of leptin in induction of chronic inflammatory processes, autoimmune pathologies, type 2 diabetes and cancer. An elevated blood level of the hormone is considered as a risk factor for different neoplasm developmentObjective. Analysis of the hormone leptin (Lep), the long and short isoforms of its receptor (LepR1 and LepR2) expression in blood, tumor cells and normal skin fibroblasts in the patients with metastatic cutaneous melanoma (CM) with various clinico-pathological characteristics for prognostic assessment.Materials and methods. 15 patients with metastatic CM (10 women and 5 men, aged 22 to 67 years with body mass from normal to obese) have been studied. The expression of Lep / LepR in the patient and donor blood sera, tumor and normal skin fibroblasts were determined using enzyme-linked immunosorbent assay (ELISA) and RT PCR using total RNAs isolated from pairs of tumor samples and normal tissue.Results. Average level of leptin in the blood of CM patients and in tumor cells exceeds the normal one. Concentration of lepin in female CM patients was higher than in male patients. The expression level of Lep and LepR1 genes (but not LepR2) in tumor cells was relatively higher than in normal skin fibroblasts of these patients, and above the level of GAPDH gene expression. In the female patients with overweight (body mass index = 25,00β29,99 kg/m2 ) there was a trend to higher concentrations of leptin in the blood in comparison of the patients with normal body mass and leptin level in the sera of male CM patients. Earlier revealed relationship between the concentration of leptin in blood and the level of expression of the long isoform of its receptor in tumor cells is confirmed.ΠΠ΅ΠΏΡΠΈΠ½ β ΠΌΠ½ΠΎΠ³ΠΎΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΠΉ Π³ΠΎΡΠΌΠΎΠ½ Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ ΡΠΈΡΠΎΠΊΠΈΠ½ΠΎΠ², ΠΊΠΎΡΠΎΡΡΠΉ ΡΠ΅Π³ΡΠ»ΠΈΡΡΠ΅Ρ Π²Π°ΠΆΠ½Π΅ΠΉΡΠΈΠ΅ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΠ΅ ΠΏΡΡΠΈ ΠΈ ΠΌΠΎΠΆΠ΅Ρ ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°ΡΡ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΡ, ΠΈΠ½Π²Π°Π·ΠΈΡ, Π°Π½Π³ΠΈΠΎΠ³Π΅Π½Π΅Π· ΠΈ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΠΉ ΡΠΎΡΡ. ΠΠ΅ΠΏΡΠΈΠ½ ΠΈΠ³ΡΠ°Π΅Ρ Π²Π°ΠΆΠ½ΡΡ ΡΠΎΠ»Ρ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΠΌΠ΅ΡΠ°Π±ΠΎΠ»ΠΈΠ·ΠΌΠ°, ΡΠ½Π΅ΡΠ³Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΎΠ±ΠΌΠ΅Π½Π° ΠΈ ΡΡΠ½ΠΊΡΠΈΠΉ Π½Π΅ΠΉΡΠΎΡΠ½Π΄ΠΎΠΊΡΠΈΠ½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ, Π²ΠΊΠ»ΡΡΠ°Ρ Π³ΠΈΠΏΠΎΡΠΈΠ·, Π³ΠΈΠΏΠΎΡΠ°Π»Π°ΠΌΡΡ ΠΈ Π½Π°Π΄ΠΏΠΎΡΠ΅ΡΠ½ΠΈΠΊΠΈ, Π° ΡΠ°ΠΊΠΆΠ΅ Π² ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΈΠΌΠΌΡΠ½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ. Π ΠΏΠΎΡΠ»Π΅Π΄Π½Π΅Π΅ Π²ΡΠ΅ΠΌΡ ΠΏΠΎΡΠ²ΠΈΠ»ΠΈΡΡ Π΄Π°Π½Π½ΡΠ΅ ΠΎ ΡΠΎΠ»ΠΈ Π»Π΅ΠΏΡΠΈΠ½Π° Π² ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
Π²ΠΎΡΠΏΠ°Π»ΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΠΏΡΠΎΡΠ΅ΡΡΠΎΠ², Π°ΡΡΠΎΠΈΠΌΠΌΡΠ½Π½ΡΡ
ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΉ, Π΄ΠΈΠ°Π±Π΅ΡΠ° 2-Π³ΠΎ ΡΠΈΠΏΠ° ΠΈ ΡΠ°ΠΊΠ°. ΠΠΎΠ²ΡΡΠ΅Π½Π½ΡΠΉ ΡΡΠΎΠ²Π΅Π½Ρ Π³ΠΎΡΠΌΠΎΠ½Π° Π² ΠΊΡΠΎΠ²ΠΈ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°Π΅ΡΡΡ ΠΊΠ°ΠΊ ΡΠ°ΠΊΡΠΎΡ ΡΠΈΡΠΊΠ° ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
Π½ΠΎΠ²ΠΎΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠΉ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β Π°Π½Π°Π»ΠΈΠ· ΡΡΠΎΠ²Π½Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π³ΠΎΡΠΌΠΎΠ½Π° Π»Π΅ΠΏΡΠΈΠ½Π° (Lep), Π΄Π»ΠΈΠ½Π½ΠΎΠΉ ΠΈ ΠΊΠΎΡΠΎΡΠΊΠΎΠΉ ΠΈΠ·ΠΎΡΠΎΡΠΌ Π΅Π³ΠΎ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° (LepR1 ΠΈ LepR2) Π² ΠΊΡΠΎΠ²ΠΈ, ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΊΠ°Ρ
ΠΈ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΡΡ
ΡΠΈΠ±ΡΠΎΠ±Π»Π°ΡΡΠ°Ρ
ΠΊΠΎΠΆΠΈ Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΌΠ΅Π»Π°Π½ΠΎΠΌΠΎΠΉ ΠΊΠΎΠΆΠΈ (ΠΠ) Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌΠΈ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠ°ΠΌΠΈ Π΄Π»Ρ ΠΏΡΠΎΠ³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΎΡΠ΅Π½ΠΊΠΈ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΎ 15 Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΠ (10 ΠΆΠ΅Π½ΡΠΈΠ½ ΠΈ 5 ΠΌΡΠΆΡΠΈΠ½, Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ 22β67 Π»Π΅Ρ Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌΠΈ ΠΈΠ½Π΄Π΅ΠΊΡΠ°ΠΌΠΈ ΠΌΠ°ΡΡΡ ΡΠ΅Π»Π° (ΠΠΠ’): ΠΎΡ Π½ΠΎΡΠΌΡ Π΄ΠΎ ΠΎΠΆΠΈΡΠ΅Π½ΠΈΡ). ΠΠΊΡΠΏΡΠ΅ΡΡΠΈΡ Lep / LepR Π² ΡΡΠ²ΠΎΡΠΎΡΠΊΠ΅ ΠΊΡΠΎΠ²ΠΈ, ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ ΠΈ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΡΡ
ΡΠΈΠ±ΡΠΎΠ±Π»Π°ΡΡΠ°Ρ
ΠΊΠΎΠΆΠΈ ΠΈ Π΄ΠΎΠ½ΠΎΡΡΠΊΠΎΠΉ ΠΊΡΠΎΠ²ΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ»ΠΈ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΈΠΌΠΌΡΠ½ΠΎΡΠ΅ΡΠΌΠ΅Π½ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° (ELISA) ΠΈ ΠΌΠ΅ΡΠΎΠ΄Π° ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½ΠΎΠΉ ΡΠ΅ΠΏΠ½ΠΎΠΉ ΡΠ΅Π°ΠΊΡΠΈΠΈ Ρ ΠΎΠ±ΡΠ°ΡΠ½ΠΎΠΉ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠ΅ΠΉ Π½Π° ΠΌΠ°ΡΡΠΈΡΠ΅ ΡΠΎΡΠ°Π»ΡΠ½ΠΎΠΉ Π ΠΠ, Π²ΡΠ΄Π΅Π»Π΅Π½Π½ΠΎΠΉ ΠΈΠ· ΠΏΠ°Ρ ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΠΈ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π ΡΡΠ΅Π΄Π½Π΅ΠΌ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ Π»Π΅ΠΏΡΠΈΠ½Π° Π² ΠΊΡΠΎΠ²ΠΈ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΠ ΠΈ Π² ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΊΠ°Ρ
ΠΏΡΠ΅Π²ΡΡΠ°Π΅Ρ ΡΡΠΈ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΠΈ Π² Π½ΠΎΡΠΌΠ΅, Π° Π΅Π³ΠΎ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡ Ρ ΠΆΠ΅Π½ΡΠΈΠ½ Ρ ΠΠ Π±ΡΠ»Π° Π²ΡΡΠ΅, ΡΠ΅ΠΌ Ρ ΠΌΡΠΆΡΠΈΠ½. Π£ΡΠΎΠ²Π΅Π½Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π³Π΅Π½Π° Lep, Π° ΡΠ°ΠΊΠΆΠ΅ LepR1 (Π½ΠΎ Π½Π΅ LepR2) Π² ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΊΠ°Ρ
ΠΎΠΊΠ°Π·Π°Π»ΡΡ ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎ Π²ΡΡΠ΅, ΡΠ΅ΠΌ Π² Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΡΡ
ΡΠΈΠ±ΡΠΎΠ±Π»Π°ΡΡΠ°Ρ
ΠΊΠΎΠΆΠΈ ΡΡΠΈΡ
ΠΆΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΈ Π²ΡΡΠ΅ ΡΡΠΎΠ²Π½Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π³Π΅Π½Π° GAPDH Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ
. Π£ Π±ΠΎΠ»ΡΠ½ΡΡ
Ρ ΠΈΠ·Π±ΡΡΠΎΡΠ½ΠΎΠΉ ΠΌΠ°ΡΡΠΎΠΉ ΡΠ΅Π»Π° (ΠΠΠ’ = 25,00β29,99 ΠΊΠ³/ΠΌ2 ) ΠΎΡΠΌΠ΅ΡΠ΅Π½Π° ΡΠ΅Π½Π΄Π΅Π½ΡΠΈΡ ΠΊ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Π»Π΅ΠΏΡΠΈΠ½Π° Π² ΠΊΡΠΎΠ²ΠΈ, ΠΏΡΠΈΡΠ΅ΠΌ Ρ ΠΆΠ΅Π½ΡΠΈΠ½ Ρ ΠΠ ΡΡΠΎΡ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Ρ ΠΏΡΠ΅Π²ΡΡΠ°Π» ΡΡΠΎΠ²Π΅Π½Ρ Π»Π΅ΠΏΡΠΈΠ½Π° Π² ΡΡΠ²ΠΎΡΠΎΡΠΊΠ΅ ΠΊΡΠΎΠ²ΠΈ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΌΡΠΆΡΠΈΠ½. ΠΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π΅Π½Π° ΡΠ°Π½Π΅Π΅ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Π½Π°Ρ Π½Π°ΠΌΠΈ Π²Π·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·Ρ ΠΌΠ΅ΠΆΠ΄Ρ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠ΅ΠΉ Π»Π΅ΠΏΡΠΈΠ½Π° Π² ΠΊΡΠΎΠ²ΠΈ ΠΈ ΡΡΠΎΠ²Π½Π΅ΠΌ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π΄Π»ΠΈΠ½Π½ΠΎΠΉ ΠΈΠ·ΠΎΡΠΎΡΠΌΡ Π΅Π³ΠΎ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° Π² ΠΎΠΏΡΡ
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