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1.
EMBO J ; 43(2): 196-224, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38177502

RESUMO

Ion channels, transporters, and other ion-flux controlling proteins, collectively comprising the "ion permeome", are common drug targets, however, their roles in cancer remain understudied. Our integrative pan-cancer transcriptome analysis shows that genes encoding the ion permeome are significantly more often highly expressed in specific subsets of cancer samples, compared to pan-transcriptome expectations. To enable target selection, we identified 410 survival-associated IP genes in 33 cancer types using a machine-learning approach. Notably, GJB2 and SCN9A show prominent expression in neoplastic cells and are associated with poor prognosis in glioblastoma, the most common and aggressive brain cancer. GJB2 or SCN9A knockdown in patient-derived glioblastoma cells induces transcriptome-wide changes involving neuron projection and proliferation pathways, impairs cell viability and tumor sphere formation in vitro, perturbs tunneling nanotube dynamics, and extends the survival of glioblastoma-bearing mice. Thus, aberrant activation of genes encoding ion transport proteins appears as a pan-cancer feature defining tumor heterogeneity, which can be exploited for mechanistic insights and therapy development.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Animais , Camundongos , Glioblastoma/patologia , Agressão , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Transcriptoma , Transporte de Íons/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Canal de Sódio Disparado por Voltagem NAV1.7/genética
2.
Obes Sci Pract ; 10(1): e741, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38404933

RESUMO

Objective: Adherence to lifestyle changes after bariatric surgery is associated with better health outcomes; however, research suggests that patients struggle to follow post-operative recommendations. This systematic review aimed to examine psychological factors associated with adherence after bariatric surgery. Methods: PubMed, PsycInfo, and Embase were searched (from earliest searchable to August 2022) to identify studies that reported on clinically modifiable psychological factors related to adherence after bariatric surgery. Retrieved abstracts (n = 891) were screened and coded by two raters. Results: A total of 32 studies met the inclusion criteria and were included in the narrative synthesis. Appointment attendance and dietary recommendations were the most frequently studied post-operative instructions. Higher self-efficacy was consistently predictive of better post-operative adherence to diet and physical activity, while pre-operative depressive symptoms were commonly associated with poorer adherence to appointments, diet, and physical activity. Findings were less inconsistent for anxiety and other psychiatric conditions. Conclusions: This systematic review identified that psychological factors such as mood disorders and patients' beliefs/attitudes are associated with adherence to lifestyle changes after bariatric surgery. These factors can be addressed with psychological interventions; therefore, they are important to consider in patient care after bariatric surgery. Future research should further examine psychological predictors of adherence with the aim of informing interventions to support recommended lifestyle changes.

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