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1.
Cancers (Basel) ; 16(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473326

RESUMO

This study aimed to evaluate the efficacy of the 2020 European Society of Gynecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) guidelines for endometrial cancer (EC). Additionally, a novel risk category incorporating clinicopathological and molecular factors was introduced. The predictive value of this new category for recurrence and survival in Korean patients with EC was assessed, and comparisons were made with the 2013 and 2016 European Society of Medical Oncology (ESMO) risk classifications. Patients with EC were categorized into the POLE-mutated (POLEmut), mismatch repair-deficient (MMRd), p53-aberrant (P53abn), and nonspecific molecular profile (NSMP) subtypes. Recurrence, survival, and adjuvant therapy were assessed according to each classification. Notably, patients with the POLEmut subtype showed no relapse, while patients with the P53abn subtype exhibited higher recurrence (31.8%) and mortality rates (31.8%). Regarding adjuvant therapy, 33.3% of low-risk patients were overtreated according to the 2020 ESGO/ESTRO/ESP guidelines. Overall and progression-free survival differed significantly across molecular classifications, with the POLEmut subtype showing the best and the P53abn subtype showing the worst outcomes. The 2020 ESGO molecular classification system demonstrated practical utility and significantly influenced survival outcomes. Immunohistochemistry for TP53 and MMR, along with POLE sequencing, facilitated substantial patient reclassification, underscoring the clinical relevance of molecular risk categories in EC management.

2.
Mol Endocrinol ; 29(6): 873-81, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25826445

RESUMO

Irisin is a novel myokine produced by skeletal muscle. However, its metabolic role is poorly understood. In the present study, irisin induced glucose uptake in differentiated skeletal muscle cells. It increased AMP-activated protein kinase (AMPK) phosphorylation and the inhibition of AMPK blocked glucose uptake. It also increased reactive oxygen species (ROS) generation. N-acetyl cysteine, a ROS scavenger, blocked irisin-induced AMPK phosphorylation. Moreover, irisin activated p38 MAPK in an AMPK-dependent manner. The inhibition and knockdown of p38 MAPK blocked irisin-induced glucose uptake. A colorimetric absorbance assay showed that irisin stimulated the translocation of glucose transporter type 4 to the plasma membrane and that this effect was suppressed in cells pretreated with a p38 MAPK inhibitor or p38 MAPK small interfering RNA. In primary cultured myoblast cells, irisin increased the concentration of intracellular calcium. STO-609, a calcium/calmodulin-dependent protein kinase kinase inhibitor, blocked irisin-induced AMPK phosphorylation, implying that calcium is involved in irisin-mediated signaling. Our results suggest that irisin plays an important role in glucose metabolism via the ROS-mediated AMPK pathway in skeletal muscle cells.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Fibronectinas/farmacologia , Glucose/metabolismo , Músculo Esquelético/citologia , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Mioblastos/enzimologia , Transporte Proteico/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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