24 research outputs found
Launching a Novel Preclinical Infrastructure: Comparative Oncology Trials Consortium Directed Therapeutic Targeting of TNFΞ± to Cancer Vasculature
Background: Under the direction and sponsorship of the National Cancer Institute, we report on the first pre-clinical trial of the Comparative Oncology Trials Consortium (COTC). The COTC is a novel infrastructure to integrate cancers that naturally develop in pet dogs into the development path of new human drugs. Trials are designed to address questions challenging in conventional preclinical models and early phase human trials. Large animal spontaneous cancer models can be a valuable addition to successful studies of cancer biology and novel therapeutic drug, imaging and device development. Methodology/Principal Findings: Through this established infrastructure, the first trial of the COTC (COTC001) evaluated a targeted AAV-phage vector delivering tumor necrosis factor (RGD-A-TNF) to Ξ±V integrins on tumor endothelium. Trial progress and data was reviewed contemporaneously using a web-enabled electronic reporting system developed for the consortium. Dose-escalation in cohorts of 3 dogs (n = 24) determined an optimal safe dose (5 x 1012 transducing units intravenous) of RGD-A-TNF. This demonstrated selective targeting of tumor-associated vasculature and sparing of normal tissues assessed via serial biopsy of both tumor and normal tissue. Repetitive dosing in a cohort of 14 dogs, at the defined optimal dose, was well tolerated and led to objective tumor regression in two dogs (14%), stable disease in six (43%), and disease progression in six (43%) via Response Evaluation Criteria in Solid Tumors (RECIST). Conclusions/Significance: The first study of the COTC has demonstrated the utility and efficiency of the established infrastructure to inform the development of new cancer drugs within large animal naturally occurring cancer models. The preclinical evaluation of RGD-A-TNF within this network provided valuable and necessary data to complete the design of first-in-man studies
ΠΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΡΠΉ ΠΌΡΠ·ΡΠΊΠ°Π»ΡΠ½ΡΠΉ ΠΊΠΎΠ½ΠΊΡΡΡ Π² ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΈΠΌΠΈΠ΄ΠΆΠ° ΡΡΡΠ°Π½Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ (Π½Π° ΠΏΡΠΈΠΌΠ΅ΡΠ΅ ΠΠ²ΡΠΎΠ²ΠΈΠ΄Π΅Π½ΠΈΡ 2017)
ΠΠ½Π½ΠΎΡΠ°ΡΠΈΡ Π²ΡΠΏΡΡΠΊΠ½ΠΎΠΉ ΠΊΠ²Π°Π»ΠΈΡΠΈΠΊΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΡ ΠΡΠ»ΠΎΠ² ΠΠΈΠΊΠΈΡΠ° Π‘Π΅ΡΠ³Π΅Π΅Π²ΠΈΡ Β«ΠΠΠΠΠ£ΠΠΠ ΠΠΠΠ«Π ΠΠ£ΠΠ«ΠΠΠΠ¬ΠΠ«Π ΠΠΠΠΠ£Π Π‘ Π Π€ΠΠ ΠΠΠ ΠΠΠΠΠΠ ΠΠΠΠΠΠ Π‘Π’Π ΠΠΠ« ΠΠ ΠΠΠΠΠΠΠΠ― (ΠΠ ΠΠ ΠΠΠΠ Π ΠΠΠ ΠΠΠΠΠΠΠΠ―-2017)Β» Π. ΡΡΠΊ. - ΠΡΠΊΠΎΠ²Π° ΠΠ»Π΅Π½Π° ΠΠ»Π°Π΄ΠΈΠΌΠΈΡΠΎΠ²Π½Π°, Π΄ΠΎΠΊΡΠΎΡ ΡΠΈΠ»ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Π½Π°ΡΠΊ, Π΄ΠΎΡΠ΅Π½Ρ ΠΠ°ΡΠ΅Π΄ΡΠ° ΡΠ²ΡΠ·Π΅ΠΉ Ρ ΠΎΠ±ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΡΡΡΡ ΠΡΠ½Π°Ρ ΡΠΎΡΠΌΠ° ΠΎΠ±ΡΡΠ΅Π½ΠΈΡ ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ: ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΡΠΉ ΠΌΡΠ·ΡΠΊΠ°Π»ΡΠ½ΡΠΉ ΠΊΠΎΠ½ΠΊΡΡΡ ΠΠ²ΡΠΎΠ²ΠΈΠ΄Π΅Π½ΠΈΠ΅ ΠΊΠ°ΠΊ ΡΠ°ΠΌΠΎΠ΅ ΠΌΠ°ΡΡΡΠ°Π±Π½ΠΎΠ΅ ΡΠ΅Π³ΡΠ»ΡΡΠ½ΠΎΠ΅ Π²ΡΡΠΎΠΊΠΎΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΡΠ½ΠΎΠ΅ ΡΠ΅Π»Π΅Π²ΠΈΠ·ΠΈΠΎΠ½Π½ΠΎΠ΅ ΠΈ ΠΌΠ΅Π΄ΠΈΠ°-ΡΠΎΠ±ΡΡΠΈΠ΅, ΠΊΠΎΡΠΎΡΠΎΠ΅ . Π Π΅ΠΆΠ΅Π³ΠΎΠ΄Π½ΠΎ Π°ΠΊΡΠ΅Π½ΡΠΈΡΡΠ΅Ρ Π²Π½ΠΈΠΌΠ°Π½ΠΈΠ΅ Π°ΡΠ΄ΠΈΡΠΎΡΠΈΠΈ Π½Π° Π½Π°ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎ-ΠΊΡΠ»ΡΡΡΡΠ½ΡΡ
ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΡΡ
ΡΡΡΠ°Π½Ρ-ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΎΡΠ° ΠΊΠΎΠ½ΠΊΡΡΡΠ°, ΡΠΎΡΠΌΠΈΡΡΠ΅Ρ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΡΠ΅ ΡΡΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΠΎΡΠΎΠΊΠΈ ΠΈ ΡΠ΅ΠΌ ΡΠ°ΠΌΡΠΌ ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΡΠ΅Ρ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠΌΠΈΠ΄ΠΆΠ° ΡΠ΅ΡΡΠΈΡΠΎΡΠΈΠΈ. ΠΠΎΠ»Π΅Π΅ ΡΠΎΠ³ΠΎ, ΠΏΠΎΠ±Π΅Π΄Π° ΡΡΡΠ°Π½Ρ-ΡΡΠ°ΡΡΠ½ΠΈΡΡ ΠΊΠΎΠ½ΠΊΡΡΡΠ° ΠΠ²ΡΠΎΠ²ΠΈΠ΄Π΅Π½ΠΈΡ Π·Π°ΡΠ°ΡΡΡΡ ΠΎΡΡΠ°ΠΆΠ°Π΅Ρ ΠΈΠ΄Π΅ΠΎΠ»ΠΎΠ³ΠΎ-ΠΏΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π²Π΅ΠΊΡΠΎΡ ΠΠ²ΡΠΎΠΏΡ ΠΈ ΠΏΠΎ ΡΡΡΠΈ Π΄Π΅Π»Π° Π²ΡΠΏΠΎΠ»Π½ΡΠ΅Ρ ΡΡΠ½ΠΊΡΠΈΡ ΠΏΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ PR ΡΡΡΠ°Π½Ρ-ΠΏΠΎΠ±Π΅Π΄ΠΈΡΠ΅Π»Ρ ΠΈ ΡΡΡΠ°Π½Ρ-Ρ
ΠΎΠ·ΡΠΉΠΊΠΈ ΠΌΠ΅ΡΠΎΠΏΡΠΈΡΡΠΈΡ. Π‘Π»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎ Π°Π½Π°Π»ΠΈΠ· ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΡ
Π½Π° ΠΌΠ΅ΡΠΎΠΏΡΠΈΡΡΠΈΠΈ ΠΊΠΎΠΌΠΌΡΠ½ΠΈΠΊΠ°ΡΠΈΠ²Π½ΡΡ
ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΉ ΡΠ²Π»ΡΠ΅ΡΡΡ Π°ΠΊΡΡΠ°Π»ΡΠ½ΡΠΌ ΠΈ Π²ΠΎΡΡΡΠ΅Π±ΠΎΠ²Π°Π½Π½ΡΠΌ Π΄Π»Ρ ΡΠΎΠ±ΡΡΠΈΠΉΠ½ΠΎΠ³ΠΎ ΠΈ ΡΡΡΡΠΎΠΈΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ PR ΠΠ±ΡΠ΅ΠΊΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ: ΠΊΠΎΠΌΠΌΡΠ½ΠΈΠΊΠ°ΡΠΈΠΎΠ½Π½ΡΠ΅ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΌΡΠ·ΡΠΊΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠΎΠ½ΠΊΡΡΡΠ° (Π½Π° ΠΏΡΠΈΠΌΠ΅ΡΠ΅ ΠΠ²ΡΠΎΠ²ΠΈΠ΄Π΅Π½ΠΈΡ Π² ΠΠΈΠ΅Π²Π΅ Π² 2017 Π³.). ΠΡΠ΅Π΄ΠΌΠ΅Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ: ΡΡΠ½ΠΊΡΠΈΡ ΡΡΠ°ΡΡΡΠ½ΠΎΠ³ΠΎ PR-ΠΌΠ΅ΡΠΎΠΏΡΠΈΡΡΠΈΡ Π² ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΈΠΌΠΈΠ΄ΠΆΠ° ΡΡΡΠ°Π½Ρ. Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ: Π΄ΠΎΠΊΠ°Π·Π°ΡΡ, ΡΡΠΎ ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΡΠΉ ΠΌΡΠ·ΡΠΊΠ°Π»ΡΠ½ΡΠΉ ΠΊΠΎΠ½ΠΊΡΡΡ ΠΠ²ΡΠΎΠ²ΠΈΠ΄Π΅Π½ΠΈΠ΅ ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΡΠ΅Ρ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠΌΠΈΠ΄ΠΆΠ° ΡΡΡΠ°Π½Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ. ΠΠ°Π΄Π°ΡΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ: ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°ΡΡ ΡΠ΅ΡΠΌΠΈΠ½ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°ΠΏΠΏΠ°ΡΠ°Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ Π½Π°ΡΡΠ½ΠΎΠΉ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ ΠΏΠΎ ΠΈΠΌΠΈΠ΄ΠΆΠΌΠ΅ΠΉΠΊΠΈΠ½Π³Ρ, Π±ΡΠ΅Π½Π΄ΠΈΠ½Π³Ρ ΠΈ ΠΈΠ²Π΅Π½Ρ-ΠΌΠ΅Π½Π΅Π΄ΠΆΠΌΠ΅Π½ΡΡ; ΠΎΠΏΡΠ΅Π΄Π΅Π»ΠΈΡΡ Π°ΠΊΡΡΠ°Π»ΡΠ½ΡΠ΅ ΠΊΠΎΠΌΠΌΡΠ½ΠΈΠΊΠ°ΡΠΈΠΎΠ½Π½ΡΠ΅ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ, ΠΏΡΠΈΠΌΠ΅Π½ΡΠ΅ΠΌΡΠ΅ Π² ΡΠ°ΠΌΠΊΠ°Ρ
ΡΠΏΠ΅ΡΠΈΠ°Π»ΡΠ½ΡΡ
ΡΠΎΠ±ΡΡΠΈΠΉ Π΄Π»Ρ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠΌΠΈΠ΄ΠΆΠ° ΡΡΡΠ°Π½Ρ; ΠΎΠΏΠΈΡΠ°ΡΡ ΡΠΎΠ»Ρ ΠΠ²ΡΠΎΠΏΠ΅ΠΉΡΠΊΠΎΠ³ΠΎ ΠΠ΅ΡΠ°ΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ Π‘ΠΎΡΠ·Π° ΠΊΠ°ΠΊ ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΎΡΠ° ΠΠ²ΡΠΎΠ²ΠΈΠ΄Π΅Π½ΠΈΡ Π² ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΈΠΌΠΈΠ΄ΠΆΠ° ΡΡΡΠ°Π½Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΊΠΎΠ½ΠΊΡΡΡΠ°; ΠΎΡΠ΅Π½ΠΈΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠ΅Π°Π»ΠΈΠ·ΠΎΠ²Π°Π½Π½ΡΡ
ΠΊΠΎΠΌΠΌΡΠ½ΠΈΠΊΠ°ΡΠΈΠ²Π½ΡΡ
ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΉ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠΌΠΈΠ΄ΠΆΠ° ΡΡΡΠ°Π½Ρ Π² ΡΠ°ΠΌΠΊΠ°Ρ
ΠΠ²ΡΠΎΠ²ΠΈΠ΄Π΅Π½ΠΈΡ; Π΄Π°ΡΡ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΈ ΠΏΠΎ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠΌΠΈΠ΄ΠΆΠ° ΡΡΡΠ°Π½Ρ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΠ²ΡΠΎΠ²ΠΈΠ΄Π΅Π½ΠΈΡ. Π’Π΅ΠΎΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠ°Ρ Π±Π°Π·Π°: Π½Π°ΡΡΠ½ΡΠ΅ ΡΡΡΠ΄Ρ Π. ΠΡΠΊΠΎΠ²ΠΎΠΉ, Π. ΠΠ°Π²ΡΡ, Π. ΠΠ°Π½ΠΊΡΡΡ
ΠΈΠ½Π°, Π. ΠΠΆΠ΅Π½Π΅ΡΠ°, Π. ΠΠ°Π²Π΅ΡΠΈΠ½ΠΎΠΉ, Π£. Π₯Π°Π»ΡΡΠ±Π°ΡΡΠ°, ΠΠΆ. ΠΠΎΠ»Π΄Π±Π»Π°ΡΡΠ° Π° ΡΠ°ΠΊΠΆΠ΅ ΡΡΡΠ΄Ρ Π. ΠΠ°ΡΡΠΌΠ°Π½Π° ΠΎ ΠΌΡΠ·ΡΠΊΠ°Π»ΡΠ½ΠΎΠΌ Π±ΠΈΠ·Π½Π΅ΡΠ΅, Π. ΠΠΆΠΎΡΠ΄Π°Π½Π° ΠΎ ΠΏΡΠΎΠ΄Π²ΠΈΠΆΠ΅Π½ΠΈΠΈ ΠΈΠΌΠΈΠ΄ΠΆΠ° ΡΡΡΠ°Π½ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΠ²ΡΠΎΠ²ΠΈΠ΄Π΅Π½ΠΈΡ ΠΈ Π΄Ρ. ΠΠΌΠΏΠΈΡΠΈΡΠ΅ΡΠΊΠ°Ρ Π±Π°Π·Π°: PR-Π΄ΠΎΠΊΡΠΌΠ΅Π½ΡΡ, ΡΠ°Π·ΠΌΠ΅ΡΠ΅Π½Π½ΡΠ΅ Π½Π° ΡΠ°ΠΉΡΠ΅ ΠΠ²ΡΠΎΠ²ΠΈΠ΄Π΅Π½ΠΈΡ ΠΈ ΠΠ²ΡΠΎΠΏΠ΅ΠΉΡΠΊΠΎΠ³ΠΎ ΠΠ΅ΡΠ°ΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ Π‘ΠΎΡΠ·Π°; Π±ΠΎΠ»Π΅Π΅ ΠΏΠΎΠ»ΡΡΠΎΡΠ° ΠΌΠΈΠ»Π»ΠΈΠΎΠ½Π° ΡΡΠ°ΡΠ΅ΠΉ ΠΎΠ± Π£ΠΊΡΠ°ΠΈΠ½Π΅ Π² Π΅Π²ΡΠΎΠΏΠ΅ΠΉΡΠΊΠΈΡ
Π‘ΠΠ, ΡΠ°Π·ΠΌΠ΅ΡΠ΅Π½Π½ΡΠ΅ Π² Π±Π°Π·Π΅ ΠΏΡΠΎΠ΅ΠΊΡΠ° ΠΌΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³Π° ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΈΠΌΠΈΠ΄ΠΆΠ° Π£ΠΊΡΠ°ΠΈΠ½Ρ Β«OkoΒ»; Π΄Π°Π½Π½ΡΠ΅ Π±Π°Π·Ρ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»ΠΎΠ² Π‘ΠΠ ΠΈ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΡΡ
ΠΌΠ΅Π΄ΠΈΠ° Factiva; Π΄Π°Π½Π½ΡΠ΅ Google.Analytics. ΠΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠ°Ρ Π·Π½Π°ΡΠΈΠΌΠΎΡΡΡ: ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π΄ΠΎΠΊΠ°Π·ΡΠ²Π°Π΅Ρ, ΡΡΠΎ ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΡΠΉ ΠΌΡΠ·ΡΠΊΠ°Π»ΡΠ½ΡΠΉ ΠΊΠΎΠ½ΠΊΡΡΡ ΠΠ²ΡΠΎΠ²ΠΈΠ΄Π΅Π½ΠΈΠ΅ ΡΠΎΡΠΌΠΈΡΡΠ΅Ρ ΠΈΠΌΠΈΠ΄ΠΆ ΡΡΡΠ°Π½Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΠΎ ΠΎΡ ΡΡΠΏΠ΅ΡΠ½ΠΎΡΡΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ ΠΊΠΎΠ½ΠΊΡΠ΅ΡΠ½ΡΡ
ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΉ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠΌΠΈΠ΄ΠΆΠ° ΡΡΡΠ°Π½Ρ. Π’Π΅Π·ΠΈΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π±ΡΠ»ΠΈ Π°ΠΏΡΠΎΠ±ΠΈΡΠΎΠ²Π°Π½Ρ Π½Π° ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΠΎΠΌ Π½Π°ΡΡΠ½ΠΎΠΌ ΡΠΎΡΡΠΌΠ΅ Β«ΠΠ΅Π΄ΠΈΠ° Π² ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠΌ ΠΌΠΈΡΠ΅. 57-Π΅ ΠΠ΅ΡΠ΅ΡΠ±ΡΡΠ³ΡΠΊΠΈΠ΅ ΡΡΠ΅Π½ΠΈΡΒ», ΠΎΠΏΡΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Ρ Π² ΡΠ±ΠΎΡΠ½ΠΈΠΊΠ΅ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»ΠΎΠ² ΡΡΠ°ΡΠ΅ΠΉ ΡΠΎΡΡΠΌΠ° ΠΈ ΠΈΠΌΠ΅ΡΡ ΡΡΠ°ΡΡΡ Π½Π°ΡΡΠ½ΠΎΠΉ ΡΡΠ°ΡΡΠΈ, ΡΠ°Π·ΠΌΠ΅ΡΠ΅Π½Π½ΠΎΠΉ Π² Π±Π°Π·Π΅ Π ΠΠΠ¦. Π‘ΡΡΡΠΊΡΡΡΠ° ΡΠ°Π±ΠΎΡΡ: Π Π°Π±ΠΎΡΠ° ΡΠΎΡΡΠΎΠΈΡ ΠΈΠ· Π²Π²Π΅Π΄Π΅Π½ΠΈΡ, 3 Π³Π»Π°Π²: Β«ΡΡΠ½ΠΊΡΠΈΡ ΡΠΏΠ΅ΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠΎΠ±ΡΡΠΈΡ Π² ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΈΠΌΠΈΠ΄ΠΆΠ° ΡΡΡΠ°Π½ΡΒ», Β«ΠΠ²ΡΠΎΠ²ΠΈΠ΄Π΅Π½ΠΈΠ΅ ΠΊΠ°ΠΊ ΡΠΏΠ΅ΡΠΈΠ°Π»ΡΠ½ΠΎΠ΅ ΡΠΎΠ±ΡΡΠΈΠ΅ ΠΠ²ΡΠΎΠΏΠ΅ΠΉΡΠΊΠΎΠ³ΠΎ ΠΠ΅ΡΠ°ΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ Π‘ΠΎΡΠ·Π°Β» ΠΈ Β«ΠΊΠΎΠΌΠΌΡΠ½ΠΈΠΊΠ°ΡΠΈΠΎΠ½Π½ΡΠΉ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π» ΠΠ²ΡΠΎΠ²ΠΈΠ΄Π΅Π½ΠΈΡ ΠΊΠ°ΠΊ ΠΏΠ»ΠΎΡΠ°Π΄ΠΊΠΈ Π΄Π»Ρ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΠΌΠΈΠ΄ΠΆΠ° ΡΡΡΠ°Π½ΡΒ», Π·Π°ΠΊΠ»ΡΡΠ΅Π½ΠΈΡ, ΡΠΏΠΈΡΠΊΠ° ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½Π½ΠΎΠΉ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ ΠΈΠ· 67 ΠΏΠΎΠ·ΠΈΡΠΈΠΉ ΠΈ 12 ΠΏΡΠΈΠ»ΠΎΠΆΠ΅Π½ΠΈΠΉ. ΠΠ±ΡΠΈΠΉ ΠΎΠ±ΡΠ΅ΠΌ 76 ΡΡΡΠ°Π½ΠΈΡ.Abstract of graduating qualification thesis Mikita Arlou INTERNATIONAL MUSIC CONTEST IN HOST COUNTRY IMAGE FORMATION (ON THE EXAMPLE OF EUROVISION 2017) Supervisor associate professor Elena Bykova, doctor of philology Department of PR in business full-time study Relevance: the international music contest Eurovision as the most wide scale regular high tech TV and Media event which annually emphasizes audience attention on national cultural features of the host country, forms tourist flows which have huge influence on territorial image formation. Besides the win of a participating in the Eurovision country often shows the ideological and political European vector and in fact serves as political PR of the winning or host country. Consequently the analysis of applied communication technologies is relevant and in-demand for event PR. Research object: communication activities of international music contest (on the example of Eurovision in Kyiv in 2017). Research subject: function of status PR event in country image formation. The aim of research: to prove that international music contest Eurovision contributes host country image formation. The tasks of research: to develop research terminology based on scientific literature on image making, branding and event management; to define actual communication technologies applied in special PR events on country image formation; to describe European Broadcasting Union role in host country image formation; to appreciate effectiveness of applied communication technologies on host country image formation in Eurovision; to give recommendations for host country image formation with the help of Eurovision. Theoretical base: scientific works written by E. Bykova, D. Gavra, A. Pankrukhin, B. Jenes, E. Kaverina, U. Halcbaur, J. Goldblatt and D. PassmanΒ΄s works on music business and P. Jordan on county image building with the help of Eurovision, etc. The empirical base: PR documents from official Eurovision and European Broadcasting Union websites; more than 1.5 million articles on Ukraine in European media stored in the base of international Ukrainian image monitoring project Oko; content of the mass media and social media base Factiva; Google.Analytics data. Practical significance: the research proves that international music contest Eurovision is relevant for the host country image formation independently of the success level of applied country image formation communication technologies. Approbation: General positions of current thesis were aprobated on international scientific forum Media in modern world and were published at the collection of articles of the forum and have the status of a scientific article posted in the RINC database. Thesis structure: Research consists of introduction, 3 chapters: Special event function in country image formation, Eurovision as EBU special event and communication potential of Eurovision as a platform for image formation; conclusion, literature list from 67 positions and 12 attachments. The total volume is 76 pages
What Differentiates Poor- and Good-Outcome Psychotherapy? A Statistical-Mechanics-Inspired Approach to Psychotherapy Research, Part Two: Network Analyses
Statistical mechanics is the field of physics focusing on the prediction of the behavior of a given system by means of statistical properties of ensembles of its microscopic elements. The authors examined the possibility of applying such an approach to psychotherapy research with the aim of investigating (a) the possibility of predicting good and poor outcomes of psychotherapy on the sole basis of the correlation pattern among their descriptors and (b) the analogies and differences between the processes of good- and poor-outcome cases. This work extends the results reported in a previous paper and is based on higher-order statistics stemming from a complex network approach. Four good-outcome and four poor-outcome brief psychotherapies were recorded, and transcripts of the sessions were coded according to Mergenthalerβs Therapeutic Cycle Model (TCM), i.e., in terms of abstract language, positive emotional language, and negative emotional language. The relative frequencies of the three vocabularies in each word-block of 150 words were investigated and compared in order to understand similarities and peculiarities between poor-outcome and good-outcome cases. Network analyses were performed by means of a cluster analysis over the sequence of TCM categories. The network analyses revealed that the linguistic patterns of the four good-outcome and four poor-outcome cases were grounded on a very similar dynamic process substantially dependent on the relative frequency of the states in which the transition started and ended (βrandom-walk-like behaviorβ, adjusted R2 = 0.729, p < 0.001). Furthermore, the psychotherapy processes revealed statistically significant changes in the relative occurrence of visited states between the beginning and the end of therapy, thus pointing to the non-stationarity of the analyzed processes. The present study showed not only how to quantitatively describe psychotherapy as a network, but also found out the main principles on which its evolution is based. The mind, from a linguistic perspective, seems to work-through psychotherapy sessions by passing from the most adjacent states and the most occurring ones. This finding can represent a fertile ground to rethink pivotal clinical concepts such as the timing of an interpretation or a comment, the clinical issue to address within a given session, and the general task of a psychotherapist: from someone who delivers a given technique toward a consultant promoting the flexibility of the clinical field and, thus, of the patientβs mind
RGD-A-<i>TNF</i> trafficking resulted in selective tumor endothelial cell localization and TNF <i>Ξ±</i> expression.
<p>(A, B) RGD-A-<i>TNF</i> selectively targeted tumor-associated vasculature (arrows) and was absent from normal tissues at 4β6 hours (A) and at 4 days (B). Magnification, 400-fold; scale bar, 100 Β΅M. Pre-treatment tumor biopsies, post-treatment tumor biopsies, and post-treatment normal tissues in dogs that received a single-dose of RGD-A-<i>TNF</i> double-stained with an anti-CD31 specific antibody plus an anti-bacteriophage specific antibody. Detection was performed with Alexa Fluor 488 (green, blood vessels), Alexa Fluor 594 (red, AAVP), and DAPI (blue, cell nuclei). (C) Pre-treatment tumor biopsies (day 0), post-treatment normal biopsies (day 4) and post-treatment tumor biopsies (day 4) were used for extraction of total RNA. RT-PCR was performed to measure transcript levels of human TNFΞ± in quadruplicate. The Y-axis represents the relative TNFΞ± expression levels in post-treatment normal biopsies and post-treatment tumor biopsies compared to pre-treatment tumor biopsies after normalization to GAPDH expression (Kruskal-Wallis Test, pβ=β0.0107). All data are presented as meansΒ±standard deviations. (DβF) Presence of RGD-A-<i>TNF</i> was evaluated in post-treatment (day 28) necropsy samples of tumor (D) and normal tissues (E, F). Tissues were stained for RGD-A-<i>TNF</i> as described earlier. RGD-A-<i>TNF</i> selectively targeted tumor-associated vasculature in post-treatment tumor samples (arrows). In contrast, the vector was not apparent in pre-treatment tumor samples or in post-treatment normal control necropsy samples (such as lung, liver, spleen or intestine) after serial administrations of RGD-A-<i>TNF</i>.</p
RGD-A-<i>TNF</i> administration resulted in objective tumor responses in dogs with spontaneous cancers.
<p>A large primary soft tissue sarcoma on the flank of Dog #2.11 is shown to feature the potential magnitude of the tumor response. Prior to therapy (day 0), the tumor measured 12.3 cm in longest diameter. At day 28, after 4 weekly infusions of RGD-A-<i>TNF</i>, the tumor measured 8.2 cm in longest diameter (a 33% regression) and a RECIST-based partial response (PR). At day 56, after a total of 8 weekly systemic infusions of RGD-A-<i>TNF</i>, the tumor measured 1.85 cm in longest diameter prior to resection. Therefore, this response equated to an 85% regression from baseline and a continued clinical PR. Upon surgical resection of the residual lesion, no viable tumor was found and a pathological complete response was determined.</p
RGD-A-<i>TNF</i> Dose Escalation Study: Patient Population and RGD-A-<i>TNF</i> Trafficking Data
<p>TU: transducing units; IF: immunoflourescent staining for presence of RGD-A-<i>TNF</i> in tumors; OCS: osteochondrosarcoma; PCT: plasma cell tumor; BCT: basal cell tumor; NST: nerve sheath tumor; STS: soft tissue sarcoma; OS: osteosarcoma; FS: fibrosarcoma; N.A.: not analyzed due to improper shipment.</p>*<p>Patient I.D.: dog is identified as participating in study 1 (dose escalation study), followed by patient number (i.e. patient 1.2 is dog 2 in study 1 and so on);</p>**<p>These two tumors originally diagnosed as soft tissue sarcomas were reclassified upon histopathologic review by a single pathologist (SN).</p
RGD-A-<i>TNF</i> Multiple Dose Study: Patient Data and Tumor Responses
<p>FS: fibrosarcoma; OS: osteosarcoma; PNST: peripheral nerve sheath tumor (malignant); SCC: squamous cell carcinoma; S-C MS: subcutaneous myxosarcoma; MLT: multi-lobular tumor; Mel: LN mets: melanoma lymph node metastases; inc.: increase; dec.: decrease; PD: progressive disease; SD: stable disease (shown in yellow); PR: partial response (shown in green); Unevaluable: due to consent withdrawal by the owner, or death or euthanasia before completion of cycle 1</p>*<p>Patient I.D.: dog is identified as participating in study 2 (fixed multiple dose study), followed by patient number (i.e. patient 2.2 is dog 2 in study 2 and so on)</p><p>Cycle 1: dogs received 4 weekly doses of RGD-A-<i>TNF</i>; Cycle 2: dogs received additional 4 weekly doses of RGD-A-<i>TNF</i></p