68 research outputs found
Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression
<p>Abstract</p> <p>Background</p> <p>Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone.</p> <p>Results</p> <p>Using parallel oligonucleotide array platforms, shared orthologues between species were identified and normalized. The osteosarcoma expression signatures could not distinguish the canine and human diseases by hierarchical clustering. Cross-species target mining identified two genes, interleukin-8 (<it>IL-8</it>) and solute carrier family 1 (glial high affinity glutamate transporter), member 3 (<it>SLC1A3</it>), which were uniformly expressed in dog but not in all pediatric osteosarcoma patient samples. Expression of these genes in an independent population of pediatric osteosarcoma patients was associated with poor outcome (p = 0.020 and p = 0.026, respectively). Validation of <it>IL-8 </it>and <it>SLC1A3 </it>protein expression in pediatric osteosarcoma tissues further supported the potential value of these novel targets. Ongoing evaluation will validate the biological significance of these targets and their associated pathways.</p> <p>Conclusions</p> <p>Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapies.</p
DNA repair deficiency biomarkers and the 70-gene ultra-high risk signature as predictors of veliparib/carboplatin response in the I-SPY 2 breast cancer trial.
Veliparib combined with carboplatin (VC) was an experimental regimen evaluated in the biomarker-rich neoadjuvant I-SPY 2 trial for breast cancer. VC showed improved efficacy in the triple negative signature. However, not all triple negative patients achieved pathologic complete response and some HR+HER2- patients responded. Pre-specified analysis of five DNA repair deficiency biomarkers (BRCA1/2 germline mutation; PARPi-7, BRCA1ness, and CIN70 expression signatures; and PARP1 protein) was performed on 116 HER2- patients (VC: 72 and concurrent controls: 44). We also evaluated the 70-gene ultra-high risk signature (MP1/2), one of the biomarkers used to define subtype in the trial. We used logistic modeling to assess biomarker performance. Successful biomarkers were combined using a simple voting scheme to refine the 'predicted sensitive' group and Bayesian modeling used to estimate the pathologic complete response rates. BRCA1/2 germline mutation status associated with VC response, but its low prevalence precluded further evaluation. PARPi-7, BRCA1ness, and MP1/2 specifically associated with response in the VC arm but not the control arm. Neither CIN70 nor PARP1 protein specifically predicted VC response. When we combined the PARPi-7 and MP1/2 classifications, the 42% of triple negative patients who were PARPi7-high and MP2 had an estimated pCR rate of 75% in the VC arm. Only 11% of HR+/HER2- patients were PARPi7-high and MP2; but these patients were also more responsive to VC with estimated pathologic complete response rates of 41%. PARPi-7, BRCA1ness and MP1/2 signatures may help refine predictions of VC response, thereby improving patient care
The Comparative Oncology Trials Consortium: Using Spontaneously Occurring Cancers in Dogs to Inform the Cancer Drug Development Pathway
Chand Khanna and colleagues describe the work of the Comparative Oncology Trials Consortium (COTC), which provides infrastructure and resources to integrate naturally occurring dog cancer models into the development of new human cancer drugs, devices, and imaging techniques
Rapamycin Pharmacokinetic and Pharmacodynamic Relationships in Osteosarcoma: A Comparative Oncology Study in Dogs
Signaling through the mTOR pathway contributes to growth, progression and chemoresistance of several cancers. Accordingly, inhibitors have been developed as potentially valuable therapeutics. Their optimal development requires consideration of dose, regimen, biomarkers and a rationale for their use in combination with other agents. Using the infrastructure of the Comparative Oncology Trials Consortium many of these complex questions were asked within a relevant population of dogs with osteosarcoma to inform the development of mTOR inhibitors for future use in pediatric osteosarcoma patients.This prospective dose escalation study of a parenteral formulation of rapamycin sought to define a safe, pharmacokinetically relevant, and pharmacodynamically active dose of rapamycin in dogs with appendicular osteosarcoma. Dogs entered into dose cohorts consisting of 3 dogs/cohort. Dogs underwent a pre-treatment tumor biopsy and collection of baseline PBMC. Dogs received a single intramuscular dose of rapamycin and underwent 48-hour whole blood pharmacokinetic sampling. Additionally, daily intramuscular doses of rapamycin were administered for 7 days with blood rapamycin trough levels collected on Day 8, 9 and 15. At Day 8 post-treatment collection of tumor and PBMC were obtained. No maximally tolerated dose of rapamycin was attained through escalation to the maximal planned dose of 0.08 mg/kg (2.5 mg/30 kg dog). Pharmacokinetic analysis revealed a dose-dependent exposure. In all cohorts modulation of the mTOR pathway in tumor and PBMC (pS6RP/S6RP) was demonstrated. No change in pAKT/AKT was seen in tumor samples following rapamycin therapy.Rapamycin may be safely administered to dogs and can yield therapeutic exposures. Modulation pS6RP/S6RP in tumor tissue and PBMCs was not dependent on dose. Results from this study confirm that the dog may be included in the translational development of rapamycin and potentially other mTOR inhibitors. Ongoing studies of rapamycin in dogs will define optimal schedules for their use in cancer and evaluate the role of rapamycin use in the setting of minimal residual disease
Prospective Molecular Profiling of Canine Cancers Provides a Clinically Relevant Comparative Model for Evaluating Personalized Medicine (PMed) Trials.
Background
Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting. Methodology
A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type. Conclusions
Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (\u3c1 \u3eweek). Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of dogs with cancer into the preclinical modeling of personalized medicine. Future comparative oncology studies optimizing the delivery of PMed strategies may aid cancer drug development
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
Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients
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
Defining the Pharmacodynamic Profile and Therapeutic Index of NHS-IL12 Immunocytokine in Dogs with Malignant Melanoma.
A compendium of canine normal tissue gene expression.
BACKGROUND: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. METHODOLOGY/PRINCIPAL FINDINGS: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species. CONCLUSIONS/SIGNIFICANCE: These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large
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