ABSTRACT
Melanoma is a deadly form of skin cancer with high rates of resistance to traditional chemotherapy and radiotherapy. BRAF inhibitors (BRAFi) can achieve initial efficacy when used to treat melanoma patients, but drug resistance and relapse are common, emphasizing the need for new therapeutic strategies. Herein, we reported that combination of dimethyl fumarate (DMF) and vemurafenib (Vem) inhibited melanoma cell proliferation more significantly and induced more cell death than single agent did both in vitro and in vivo. DMF/Vem treatment induced cell death through inhibiting the expression and transcriptional activity of NRF2 thereby resulting in more reactive oxygen species (ROS) and via inhibiting the expression of YAP, a key downstream effector of Hippo pathway. DMF/Vem treatment also reduced phosphorylation of AKT, 4EBP1, P70S6K and ERK in AKT/mTOR/ERK signaling pathways. RNA-seq analysis revealed that DMF/Vem treatment specifically suppressed 4561 genes which belong to dozens of cell signaling pathways. These results indicated that DMF/Vem treatment manifested an enhanced antitumor efficacy through inhibiting multiple cell signaling pathways, and thus would be a novel promising therapeutic approach targeted for melanoma.
ABSTRACT
Objective: This study aimed to explore the relationship among cognitive fusion, experiential avoidance, and obsessive-compulsive symptoms in patients with obsessive-compulsive disorder (OCD). Methods: A total of 118 outpatient and inpatient patients with OCD and 109 healthy participants, gender- and age-matched, were selected using cognitive fusion questionnaire (CFQ), acceptance and action questionnaire-2nd edition (AAQ-II), Yale-Brown scale for obsessive-compulsive symptoms, Hamilton anxiety scale, and Hamilton depression scale for questionnaire testing and data analysis. Results: The levels of cognitive fusion and experiential avoidance in the OCD group were significantly higher than those in the healthy control group (P < 0.05). Regression analysis results showed that, in predicting the total score of obsessive-compulsive symptoms, AAQ-II (ß = 0.233, P < 0.05) and CFQ (ß = 0.262, P < 0.01) entered the equation, which explained 17.1% variance. In predicting anxiety, only AAQ-II (ß = 0.222, P < 0.05) entered the equation, which explained 13% variance. In the prediction of depression, AAQ-II (ß = 0.412, P < 0.001) entered the equation, which explained 17.7% variance. Conclusion: Cognitive fusion and experiential avoidance may be important factors for the maintenance of OCD, and experiential avoidance can positively predict the anxiety and depression of OCD patients.
ABSTRACT
BACKGROUND: Obsessive-compulsive disorder (OCD) is a mental disease with obsessions and compulsions as its main symptom dimensions. In recent years, endophenotype (intermediate phenotype) method has been used to study OCD. This study aimed to evaluate the cognitive function for patients with OCD and search for possible endophenotype. METHODS: This study utilized a comparison control group design with 64 OCD patients, 49 healthy siblings (HS) of the patients, and 53 healthy controls. Several projects were selected to evaluate patients' cognition functions, such as reasoning, problem-solving, attention/vigilance, visual learning, speed of processing, and verbal learning. RESULTS: Results suggested that the patients with OCD and their HS have cognitive deficits in reasoning, problem-solving, trail making test, and visual learning. Significant differences were observed among the three groups of subjects in verbal learning. No significant difference was observed in attention/vigilance among the three groups. CONCLUSIONS: Our results suggest that reasoning, problem-solving, and visual learning may be candidate endophenotypes for the early diagnosis of prodrome Han Chinese patients with OCD.