1.Application of 18F-FMISO for tumor hypoxia imaging
Zhenzhen WANG ; Qiao RUAN ; Xinli XIE ; Xingmin HAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2015;35(5):410-413
Hypoxia is the combined result of tumor over-growth and vascular structural abnormalities.Hypoxia is related to tumor invasiveness,radioresistance,and chemoresistance.18F-fluoromisoni-dzole (18F-FMISO) can selectively bind to hypoxic tissues of malignant tumors,and is thus useful for imaging of tumor hypoxia in cancer diagnosis and treatment.This review summarizes the state-of-art research of 18F-FMISO in comparison with other hypoxic agents when applied to animals and clinical studies.
2.Hypoxic condition monitoring and treatment evaluation for non-small cell lung cancer before and after radiotherapy by 18F-FMISO PET/CT
Zhenzhen WANG ; Xiaotian LI ; Qiao RUAN ; Wei FU ; Yanpeng LI ; Xingmin HAN ; Xueqin ZHAO ; Yu CHEN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2019;39(5):262-265
Objective To evaluate the changes of hypoxic conditions in non-small cell lung cancer (NSCLC) patients before and after radiotherapy and assess the value of 18F-fluoromisonidzaole (FMISO)PET/CT for radiotherapy efficacy evaluation.Methods A total of 21 NSCLC patients (15 males,6 females,age 30-74 years) from January 2014 to October 2016 were prospectively enrolled.18F-FMISO PET/CT was performed before and after radiotherapy,and all patients underwent 18F-fluorodeoxyglucose (FDG)PET/CT before radiotherapy.Routine chest CT was performed at the 3rd and 6th month after radiotherapy.The maximum standardized uptake value (SUVmax) of tumor and muscle,tumor volume and hypoxic volume (HV) were measured.Tumor-to-muscle (T/M) value of 18F-FMISO was calculated,and T/M ≥ 1.3 was considered as the hypoxia cut-off value.Data were analyzed using Pearson correlation,paired t test,signed rank sum test and Wilcoxon rank sum test.Results Totally 81.0%(17/21) of NSCLC patients had hypoxia.There were significant positive correlations between 18F-FMISO T/M value and tumor volume or 18F-FDG SUVmax(r:0.72,0.60,both P<0.05).The T/M value after radiotherapy was significantly lower than that before radiotherapy (1.42± 1.12 vs 2.08±0.71;t =3.62,P<0.05),and median HV was also significantly lower than that before radiotherapy (6.53 vs 12.41 cm3;z =-3.83,P<0.05).The median T/M values of effective group (n =14) and ineffective group (n =7) before radiotherapy were significantly different (2.14 vs 2.87;z=-2.27,P<0.05),and the median HV of 2 groups before radiotherapy was also significantly different (6.43 vs 10.20 cm3;z=-2.14,P<0.05).Conclusions Most NSCLC patients have hypoxia before radiotherapy.The larger tumor volume,the higher degree of hypoxia.Radiotherapy can alleviate the hypoxia of tumors.18F-FMISO PET/CT imaging before radiotherapy can be used to predict the efficacy of patients with NSCLC.
3.Chronic psychological stress aggravates intestinal barrier damage and promotes enteritis development through inhibiting Wnt/β-catenin pathway
Sha LI ; Zhenzhen RUAN ; Guangran HU ; Changqing XU ; Jing YANG ; Zhaopeng WANG ; Wengang SONG ; Li GE
Chinese Journal of Microbiology and Immunology 2023;43(1):35-46
Objective:To investigate the mechanism by which chronic psychological stress aggravates intestinal barrier damage and promotes the development of enteritis through inhibiting Wnt/β-catenin pathway, so as to provide a new therapeutic strategy for the clinical diagnosis and treatment of inflammatory bowel disease (IBD).Methods:A comorbidity model of chronic psychological stress and enteritis was established using C57BL/6J mice. HE staining was used to analyze the effects of chronic psychological stress on the intestinal pathological damage in mice with enteritis. ELISA was used to detect the expression of proinflammatory cytokines. The ultrastructural changes of colonic cells and the state of intestinal mucus layer were observed under transmission electron microscope and scanning electron microscope. The secretion of mucoprotein 2 (MUC2) and the expression of cell proliferation marker Ki67 were detected by immunofluo rescence staining. The numbers of goblet cells were detected by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Western blot was performed to analyze the expression of tight junction protein between intestinal epithelial cells, β-catenin which was a key protein of Wnt/β-catenin pathway maintaining crypt proliferation, and downstream protein c-myc.Results:The sugar water consumption ratio decreased, but tail suspension immobility time, the swimming immobility time and the expression of corticotropin releasing hormone (CRH) in hypothalamus increased (all P<0.05) in the stress group as compared with those in the control group. Chronic psychological stress promoted weight loss and colonic shortening in mice with enteritis, exacerbated pathological damage and enhanced the release of pro-inflammatory factors. Moreover, increased disappearance of intestinal epithelial microvilli and severe cellular ultrastructural damage were also observed in the stress+ dextran sulfate sodium salt (DSS) group. There was no pathological damage in the control and stress groups. Chronic psychological stress aggravated intestinal barrier injury and inhibited intestinal barrier repair by inhibiting Wnt/β-catenin pathway. Conclusions:In the mouse model of DSS-induced enteritis, chronic psychological stress preconditioning inhibited the Wnt/β-catenin pathway, weakened the repair ability of intestinal epithelium, aggravated the loss of mucus layer of intestinal barrier and the damage of tight junction structure, and promoted the development of enteritis. In the absence of enteritis, chronic psychological stress had no significant effects on the Wnt/β-catenin pathway and the intestinal barrier.