Tour agencies in Curitiba /PR - Brazil and their social representaions as a result of technological innovations

Las agencias de viajes y turismo experimentan desde los últimos años del siglo XX, hasta la actualidad transformaciones tecnológicas y también en las actividades laborales. Las innovaciones tecnológicas han provocado un aumento de la competencia y cambios en el mercado facilitados por la llegada de Internet y las tecnologías de la información y la comunicación (TIC). A partir de este análisis, esta investigación tuvo como objetivo, identificar las Representaciones Sociales (RS) de los Agentes de Viajes (AV) en relación con las innovaciones tecnológicas. El diseño de este estudio se basó en la investigación documental y bibliográfica, con un enfoque cualitativo y el uso de entrevistas semiestructuradas. Las Representaciones Sociales de los profesionales de las agencias, señalan las necesidades de una constante capacitación del personal e inversiones en tecnología para permanecer en el segmento de agencias de viajes y turismo.Since the last years of the 20th century, travel and tourism agencies have undergone technologi‐ cal transformations and changes in their work activities. Technological innovations have led to increased competition and market changes facilitated by the advent of the Internet and information and communica‐ tion technologies (ICT). Based on this analysis, this research aimed at identifying the Social Representations (SR) of Travel Agents (TAs) in relation to technological innovations. The design of this study was based on documentary and bibliographic research, with a qualitative approach and the use of semi‐structured inter‐ views. The Social Representations of agency professionals indicate the need for constant staff training and investment in technology in order to remain in the travel and tourism agency segment

REPRESENTATIVIDADE DO MERCADO DE HOSPEDAGEM DE CAMPO GRANDE-MS NOS CANAIS DE DISTRIBUIÇÃO ACESSADOS PELAS TECNOLOGIAS DE INFORMAÇÃO E COMUNICAÇÃO (TICS)

Entre os canais de distribuição destacam-se as tecnologias de informação e comunicação [TICs], importantes ferramentas para os Meios de Hospedagem [MH]. O estudo teve como objetivo mensurar os dados quantitativos de distribuição e inovação nos MH da Cidade de Campo Grande, Estado de Mato Grosso do Sul. Utilizou-se de uma metodologia quali-quantitativa de análise de dados do CADASTUR e das On Line Travel Agencies [OTAs]. Identificou-se a existência de vendas de hospedagem na plataforma do AIRBNB e dependência das OTAs dos MH de Campo Grande/MS

Preclinical and clinical evaluation of German-sourced ONC201 for the treatment of H3K27M-mutant diffuse intrinsic pontine glioma

Background Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood brainstem tumor for which radiation is the only treatment. Case studies report a clinical response to ONC201 for patients with H3K27M-mutant gliomas. Oncoceutics (ONC201) is only available in the United States and Japan; however, in Germany, DIPG patients can be prescribed and dispensed a locally produced compound-ONC201 German-sourced ONC201 (GsONC201). Pediatric oncologists face the dilemma of supporting the administration of GsONC201 as conjecture surrounds its authenticity. Therefore, we compared GsONC201 to original ONC201 manufactured by Oncoceutics Inc. Methods Authenticity of GsONC201 was determined by high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Biological activity was shown via assessment of on-target effects, in vitro growth, proliferation, and apoptosis analysis. Patient-derived xenograft mouse models were used to assess plasma and brain tissue pharmacokinetics, pharmacodynamics, and overall survival (OS). The clinical experience of 28 H3K27M+ mutant DIPG patients who received GsONC201 (2017-2020) was analyzed. Results GsONC201 harbored the authentic structure, however, was formulated as a free base rather than the dihydrochloride salt used in clinical trials. GsONC201 in vitro and in vivo efficacy and drug bioavailability studies showed no difference compared to Oncoceutics ONC201. Patients treated with GsONC201 (n = 28) showed a median OS of 18 months (P = .0007). GsONC201 patients who underwent reirradiation showed a median OS of 22 months compared to 12 months for GsONC201 patients who did not (P = .012). Conclusions This study confirms the biological activity of GsONC201 and documents the OS of patients who received the drug; however, GsONC201 was never used as a monotherapy

ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma

Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG. However, further work is needed to identify the mechanisms of response of DIPGs to ONC201 treatment and to determine whether recurring genomic features influence response. Using a systems-biological approach, we showed that ONC201 elicits potent agonism of the mitochondrial protease ClpP to drive proteolysis of electron transport chain and tricarboxylic acid cycle proteins. DIPGs harboring PIK3CA-mutations showed increased sensitivity to ONC201, while those harboring TP53-mutations were more resistant. Metabolic adaptation and reduced sensitivity to ONC201 was promoted by redox-activated PI3K/Akt signaling, which could be counteracted using the brain penetrant PI3K/Akt inhibitor, paxalisib. Together, these discoveries coupled with the powerful anti-DIPG/DMG pharmacokinetic and pharmacodynamic properties of ONC201 and paxalisib have provided the rationale for the ongoing DIPG/DMG phase II combination clinical trial NCT05009992

Blockade of ROS production inhibits oncogenic signaling in acute myeloid leukemia and amplifies response to precision therapies

Mutations in the type III receptor tyrosine kinase FLT3 are frequent in patients with acute myeloid leukemia (AML) and are associated with a poor prognosis. AML is characterized by the overproduction of reactive oxygen species (ROS), which can induce cysteine oxidation in redox-sensitive signaling proteins. Here, we sought to characterize the specific pathways affected by ROS in AML by assessing oncogenic signaling in primary AML samples. The oxidation or phosphorylation of signaling proteins that mediate growth and proliferation was increased in samples from patient subtypes with FLT3 mutations. These samples also showed increases in the oxidation of proteins in the ROS-producing Rac/NADPH oxidase-2 (NOX2) complex. Inhibition of NOX2 increased the apoptosis of FLT3-mutant AML cells in response to FLT3 inhibitors. NOX2 inhibition also reduced the phosphorylation and cysteine oxidation of FLT3 in patient-derived xenograft mouse models, suggesting that decreased oxidative stress reduces the oncogenic signaling of FLT3. In mice grafted with FLT3 mutant AML cells, treatment with a NOX2 inhibitor reduced the number of circulating cancer cells, and combining FLT3 and NOX2 inhibitors increased survival to a greater extent than either treatment alone. Together, these data raise the possibility that combining NOX2 and FLT3 inhibitors could improve the treatment of FLT3 mutant AML