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1.
Oxid Med Cell Longev ; 2019: 5813985, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396300

RESUMO

BACKGROUND: The mechanisms of crosstalk between depression and gastric cancer (GC) remain ill defined. Given that reactive oxygen species (ROS) is involved in the pathophysiology of both GC and depression, we try to explore the activities of ROS in the development of GC and GC-related depression. METHODS: 110 patients with newly diagnosed GC were recruited in our study. The clinical characteristics of these patients were recorded. Inflammation and oxidative stress markers were detected by ELISA. The depression status of patients with GC was assessed during follow-up. The association between ROS, ABL1, and inflammation factors was evaluated in H2O2-treated GC cell lines and The Cancer Genome Atlas (TCGA) database. The effect of ABL1 on inflammation was detected with Imatinib/Nilotinib-treated GC cell lines. A chronic mild stress- (CMS-) induced patient-derived xenograft (PDX) mice model was established to assess the crosstalk between depression and GC. RESULTS: Depression was correlated with poor prognosis of patients with GC. GC patients with depression were under a high level of oxidative status as well as dysregulated inflammation. In the CMS-induced GC PDX mice model, CMS could facilitate the development of GC. Additionally, tumor bearing could induce depressive-like behaviors of mice. With the treatment of ROS, the activities of ABL1 and inflammatory signaling were enhanced both in vitro and in vivo, and blocking the activities of ABL1 inhibited inflammatory signaling. CONCLUSIONS: ROS-activated ABL1 mediates inflammation through regulating NF-κB1 and STAT3, which subsequently leads to the development of GC and GC-related depression.


Assuntos
Depressão/etiologia , Proteínas Proto-Oncogênicas c-abl/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Neoplasias Gástricas/diagnóstico , 8-Hidroxi-2'-Desoxiguanosina/sangue , Animais , Antineoplásicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Depressão/metabolismo , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Mesilato de Imatinib/farmacologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Nus , Prognóstico , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/complicações
2.
Cancer Lett ; 319(1): 118-24, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22252117

RESUMO

Lung cancer is the leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is one of the predominant histological subtypes of lung cancer. Detecting lung cancer at an early stage is essential for successful therapy and increasing survival. There are still no satisfactory biomarkers for the early detection of lung cancer. In this study, tumour tissue paired with tumour-adjacent normal bronchial epithelial tissue was obtained from patients with squamous cell lung carcinoma without metastasis. The proteins extracted from the cell membrane were separated by two-dimensional polyacrylamide gel electrophoresis (2-DE) and were analysed with the Image Master two-dimensional platinum software. Twenty-five significantly different protein spots were selected and identified with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). A total of 19 proteins were successfully identified. Twelve proteins were up-regulated, and seven proteins were down-regulated in the cancerous tissue compared with the tumour-adjacent normal tissue. One up-regulated protein and one down-regulated protein in squamous cell lung carcinoma were verified by Western blot analysis and RT-PCR; the results were consistent with the 2-DE analysis. In conclusion, membrane proteomics identified a number of candidate biomarker proteins that were differentially expressed between squamous cell lung cancer tissue and adjacent normal tissue. These biomarker candidates have the potential to elucidate the underlying pathogenesis of squamous cell lung cancer.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/química , Neoplasias Pulmonares/química , Idoso , Feminino , Humanos , Pulmão/química , Masculino , Pessoa de Meia-Idade , Proteômica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
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