DMF Activates NRF2 to Inhibit the Pro-Invasion Ability of TAMs in Breast Cancer.

Tumor-associated macrophages (TAMs) account for more than 50% of the cells in the tumor immune microenvironment of patients with breast cancer. A high TAM density is associated with a poor clinical prognosis. Targeting TAMs is a promising therapeutic strategy because they promote tumor growth, development, and metastasis. In this study, we found that dimethyl formamide (DMF) significantly inhibited the tumor invasion-promoting ability of TAMs in the co-culture system and further showed that DMF functioned by reducing reactive oxygen species (ROS) production in TAMs. The orthotopic 4T1 cell inoculation model and the spontaneous mouse mammary tumor virus-polyoma middle tumor-antigen tumor model were used to evaluate the antitumor effect of DMF. The results showed that DMF significantly inhibited tumor metastasis and increased T-cell infiltration into the tumor microenvironment. Mechanistically, NRF2 activation was necessary for DMF to exert its function, and DMF can play a role in breast cancer as an anticancer drug targeting TAMs.

miR-25 is upregulated before the occurrence of esophageal squamous cell carcinoma.

MicroRNAs (miRNAs) are potential biomarkers for cancer detection including esophageal squamous cell carcinoma (ESCC); however, little is known about their expression profile and diagnostic impact in esophageal squamous cell intraepithelial neoplasia, the pathological precancerous lesion of ESCC. In this study, we examined the expression levels of eight miRNAs that were reported to be deregulated in ESCC, including miR-25, let-7a, miR-100, miR-133a, miR-223, miR-375, miR-483-5p and miR-1322, in 30 pairs of esophageal squamous cell neoplasia lesion tissues and corresponding adjacent normal tissues using quantitative real-time PCR (qRT-PCR). Differential expression of miRNAs was further examined by in situ hybridization. Furthermore, the deregulated miRNAs were also measured in serum and serum exosome samples of these patients. miR-25, an oncomir that had been reported to be upregulated in ESCC tissues, were found to be overexpressed in esophageal squamous cell intraepithelial neoplasia lesions (66.7%, 20/30) compared to adjacent normal tissues (P < 0.05), while the other seven miRNAs did not show a significant difference between the lesions and controls. The miR-25 signal was stronger in lesion tissues than in normal tissues according to in situ hybridization. The concentrations of miR-25 in both serum and exosome samples of patients were not significantly different from those of healthy individuals. These findings suggested that the overexpression of miR-25 in esophageal squamous cell intraepithelial neoplasia lesions might be a promising early biomarker candidate for the prediction of ESCC.

Serum platelet factor 4 is a reliable activity parameter in adult patients with inflammatory bowel disease: A pilot study.

To investigate the diagnostic utility of serum platelet factor 4 (PF4) levels and to assess its accuracy in detecting inflammatory bowel disease activity.This study included 45 patients with ulcerative colitis (UC), 45 patients with Crohn disease (CD), and 30 control subjects at Jinling Hospital between May 2014 and July 2015. Laboratory tests measured white blood count, C-reactive protein, erythrocyte sedimentation rate, and platelet count. PF4 was examined by enzyme-linked immunosorbent assays. Patients were divided into 2 groups according to disease activity: active and inactive.Median PF4 values dramatically increased in UC and CD patients compared with the healthy group (UC: 26.64 [20.00-36.22] mg/mL vs 20.02 [14.63-26.83] mg/mL, P = 0.002; CD: 25.56 [18.57-36.36] mg/mL vs 20.02 [14.63-26.83] mg/mL, P = 0.014); however, the serum PF4 levels between UC and CD failed to show a significant difference (26.64 [20.00-36.22] mg/mL vs 25.56 [18.57-36.36] mg/mL, P = 0.521). Furthermore, serum PF4 levels were elevated in both UC and CD patients with active disease (UC: 20.19 [14.89-23.53] mg/mL vs 28.86 [22.57-37.29] mg/mL, P < 0.001; CD: 18.33 [16.72-25.77] mg/mL vs 34.38 [22.58-39.92] mg/mL, P < 0.001). Multivariate analysis revealed higher PF4 level as an independent predictor of disease activity in UC and CD patients (UC: odds ratio 30.375, P = 0.002; CD: odds ratio 54.167, P < 0.001). The cut-off level of PF4 for distinguishing active from inactive UC patients was 24.1 mg/mL. While in CD patients, the cut-off level of PF4 was 19.24 mg/mL.Serum PF4 levels could be a potential biomarker for monitoring the disease activity of inflammatory bowel disease.