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1.
Chinese Journal of Lung Cancer ; (12): 310-318, 2023.
Artigo em Chinês | WPRIM | ID: wpr-982161

RESUMO

Spindle assembly checkpoint (SAC) is a protective mechanism for cells to undergo accurate mitosis. SAC prevented chromosome segregation when kinetochores were not, or incorrectly attached to microtubules in the anaphase of mitosis, thus avoiding aneuploid chromosomes in daughter cells. Aneuploidy and altered expression of SAC component proteins are common in different cancers, including lung cancer. Therefore, SAC is a potential new target for lung cancer therapy. Five small molecule inhibitors of monopolar spindle 1 (MPS1), an upstream component protein of SAC, have entered clinical trials. This article introduces the biological functions of SAC, summarizes the abnormal expression of SAC component proteins in various cancers and the research progress of MPS1 inhibitors, and expects to provide a reference for the future development of lung cancer therapeutic strategies targeting SAC components.
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Assuntos
Humanos , Proteínas de Ciclo Celular/metabolismo , Fuso Acromático/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Pontos de Checagem da Fase M do Ciclo Celular/genética , Neoplasias Pulmonares/metabolismo
2.
Journal of Neurogastroenterology and Motility ; : 611-622, 2019.
Artigo em Inglês | WPRIM | ID: wpr-765963

RESUMO

BACKGROUND/AIMS: Gastrointestinal (GI) symptoms may develop when we fail to adapt to various stressors of our daily life. Central oxytocin (OXT) can counteract the biological actions of corticotropin-releasing factor (CRF), and in turn attenuates stress responses. Administration (intracerebroventricular) of OXT significantly antagonized the inhibitory effects of chronic complicated stress (CCS) on GI dysmotility in rats. However, intracerebroventricular administration is an invasive pathway. Intranasal administration can rapidly deliver peptides to the brain avoiding stress response. The effects of intranasal OXT on hypothalamus-pituitary-adrenal axis and GI motility in CCS conditions have not been investigated. METHODS: A CCS rat model was set up, OXT 5, 10, or 20 μg were intranasal administered, 30 minutes prior to stress loading. Central CRF and OXT expression levels were analyzed, serum corticosterone and OXT concentrations were measured, and gastric and colonic motor functions were evaluated by gastric emptying, fecal pellet output, and motility recording system. RESULTS: Rats in CCS condition showed significantly increased CRF expression and corticosterone concentration, which resulted in delayed gastric emptying and increased fecal pellet output, attenuated gastric motility and enhanced colonic motility were also recorded. OXT 10 μg or 20 μg significantly reduced CRF mRNA expression and the corticosterone concentration, OXT 20 μg also helped to restore GI motor dysfunction induced by CCS. CONCLUSION: Intranasal administration of OXT has an anxiolytic effect and attenuates the hypothalamus-pituitary-adrenal axis in response to CCS, and gave effects which helped to restore GI dysmotility, and might be a new approach for the treatment of stress-induced GI motility disorders.


Assuntos
Animais , Ratos , Administração Intranasal , Ansiolíticos , Encéfalo , Colo , Corticosterona , Hormônio Liberador da Corticotropina , Esvaziamento Gástrico , Motilidade Gastrointestinal , Modelos Animais , Ocitocina , Peptídeos , RNA Mensageiro
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