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1.
Front Endocrinol (Lausanne) ; 13: 897956, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600589

RESUMO

Purpose: Poor adherence to recombinant human growth hormone (r-hGH) treatment presents a significant barrier to achieving optimal growth outcomes. It is important to identify and address the treatment adherence-related needs of children prescribed r-hGH treatment, and develop new approaches to improve adherence. We aimed to measure the impact of the TUITEK® patient support programme, a multi-component personalized service intervention, on caregivers' knowledge, beliefs, and perceptions of short stature and adherence to its treatment. Patients and Methods: The evaluation of the TUITEK® patient support programme was conducted among 31 caregivers of children with short stature and receiving r-hGH treatment via the easypod™ auto-injector device in Taiwan. Caregivers within the 'high risk' category for knowledge, beliefs and perception factors influencing adherence to r-hGH treatment (disease and treatment coherence, emotional burden, self-administration, and treatment-related anxiety) were identified via the TUITEK® personalization questionnaire and followed up with bi-weekly telephone calls by a nurse practitioner over a 3-month period. A Wilcoxon signed-rank test was used to compare changes in questionnaire-based scoring patterns between baseline and follow-up. Results: Between baseline and follow-up, the percentage of caregivers scoring as 'high risk' for emotional burden reduced by 37%; there was an improvement in confidence of self-administration by 57% and the percentage of caregivers scoring as 'high risk' for treatment-related anxiety reduced by 52%. At follow-up, all caregivers classified as 'high risk' within the disease and treatment coherence item at baseline moved into the 'low risk' category. Statistically significant changes in questionnaire scores between baseline and follow-up for disease and treatment understanding, emotional burden, self-administration, and treatment-related anxiety were also observed. Conclusion: These findings indicate that the TUITEK® patient support programme can positively address disease and treatment-related barriers amongst caregivers regarding optimal adherence of their children to r-hGH treatment, which has the potential to positively impact on adherence levels and patient clinical health outcomes.


Assuntos
Hormônio do Crescimento Humano , Cuidadores , Criança , Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Proteínas Recombinantes/uso terapêutico , Taiwan
2.
Biochim Biophys Acta Mol Cell Res ; 1868(2): 118891, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33096142

RESUMO

Lung cancer is the leading cause of cancer death, and therefore the discovery of novel therapeutic targets is crucial. P21-activated kinase (PAK1) is an important oncogene involved in the signaling of actin cytoskeleton organization. Although PAK1 inhibition has been shown to suppress cancer progression, specific PAK1 inhibitors are not available due to the complex structure and insufficient understanding of this kinase. The Hippo signaling effector TAZ is known to be elevated in multiple human cancers and to promote cancer metastasis. This study aimed to explore the role of TAZ in regulating the tumor suppressor ankyrin repeat domain 52 (ANKRD52) and PAK1 activity. A negative correlation between TAZ and ANKRD52 was observed, with knockdown of TAZ leading to enhanced ANKRD52 promoter activity and increased mRNA levels. Moreover, reduced ANKRD52 levels were associated with late-stage lung cancer. Knockdowns of ANKRD52 resulted in elevated cell mobility, while forced ANKRD52 expression attenuated cell mobility. ANKRD52 is a subunit of the protein phosphatase 6 (PP6) holoenzyme. Mass spectrometry analysis revealed the interaction between PAK1 and the ANKRD52-PP6 complex. Knockdown of ANKRD52 or PP6c resulted in upregulated PAK1 phosphorylation. Our study demonstrates that the novel tumor suppressor protein ANKRD52 is transcriptionally inhibited by TAZ, regulating cell mobility through interactions with PP6c and dephosphorylation of PAK1.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Transdução de Sinais/genética , Transativadores/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Quinases Ativadas por p21/metabolismo , Adenocarcinoma de Pulmão/patologia , Animais , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfoproteínas Fosfatases/genética , Fosforilação/genética , Regiões Promotoras Genéticas , RNA Interferente Pequeno/metabolismo , Transativadores/genética , Ativação Transcricional/genética , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Transfecção , Proteínas Supressoras de Tumor/genética , Ensaios Antitumorais Modelo de Xenoenxerto
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