Rab5a Promotes Cytolethal Distending Toxin B-Induced Cytotoxicity and Inflammation.

The cytolethal distending toxin B subunit (CdtB) induces significant cytotoxicity and inflammation in many cell types that are involved in the pathogenesis of postinfectious irritable bowel syndrome (PI-IBS). However, the underlying mechanisms remain unclear. This study tested the potential role of Rab small GTPase 5a (Rab5a) in the process. We tested mRNA and protein expression of proinflammatory cytokines (interleukin-1ß [IL-1ß] and IL-6) in THP-1 macrophages by quantitative PCR (qPCR) and enzyme-linked immunosorbent assays (ELISAs), respectively. In the primary colonic epithelial cells, Cdt treatment induced a CdtB-Rab5a-cellugyrin association. Rab5a silencing, by target small hairpin RNAs (shRNAs), largely inhibited CdtB-induced cytotoxicity and apoptosis in colon epithelial cells. CRISPR/Cas9-mediated Rab5a knockout also attenuated CdtB-induced colon epithelial cell death. Conversely, forced overexpression of Rab5a intensified CdtB-induced cytotoxicity. In THP-1 human macrophages, Rab5a shRNA or knockout significantly inhibited CdtB-induced mRNA expression and production of proinflammatory cytokines (IL-1ß and IL-6). Rab5a depletion inhibited activation of nuclear factor-κB (NF-κB) and Jun N-terminal protein kinase (JNK) signaling in CdtB-treated THP-1 macrophages. Rab5a appears essential for CdtB-induced cytotoxicity in colonic epithelial cells and proinflammatory responses in THP-1 macrophages.

A pilot study of radiomics technology based on X-ray mammography in patients with triple-negative breast cancer.

PURPOSE: To explore the radiomics features of triple negative breast cancer (TNBC) and non-triple negative breast cancer (non-TNBC) based on X-ray mammography, and to differentiate the two groups of cases. MATERIALS AND METHODS: Preoperative mammograms of 120 patients with breast ductal carcinoma confirmed by surgical pathology were retrospectively analyzed, which include 30 TNBC and 90 non-TNBC patients. The manual segmentation of breast lesions was performed by ITK-SNAP software and 12 radiomics features were extracted by Omni-Kinetics software. The differences of these radiomics features between TNBC and non-TNBC groups were compared, and the receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value of each radiomics parameter for differentiating TNBC from non-TNBC, and the corresponding area under the curve (AUC), sensitivity and specificity were obtained. RESULTS: There were statistically significant differences for 4 radiomics features between TNBC and non-TNBC datasets (P < 0.05). They were the roundness, concavity, gray average and skewness of breast lesions. Compared with non-TNBC, TNBC cases have following characteristics of (1) more round with the roundness of 0.621 vs. 0.413 (P < 0.001), (2) more regular with the concavity of 0.087 vs. 0.141 (P < 0.01), (3) higher density or gray average (67.261 vs. 56.842, P < 0.05), and (4) lower skewness (- 0.837 vs.- 0.671, P = 0.034). AUCs of ROC curves computed using features of the roundness and concavity were both larger than 0.70. CONCLUSION: Radiomics features based on X-ray mammography may be helpful to distinguish between TNBC and non-TNBC, which were associated with breast tumor histology.

An application study of low-dose computed tomography perfusion imaging (LDCTPI) in breast cancer and breast fibroadenoma.

PURPOSE: To explore the characteristics of breast cancer and breast fibroadenoma using low-dose computed tomography perfusion imaging (LDCTPI) including specific perfusion parameter values, and seek the potential clinical applications in cancer prognosis assessment. MATERIALS AND METHODS: Fifty patients including 30 diagnosed with breast cancer and 20 with breast fibroadenoma, as well as 15 control subjects with normal breasts were studied prospectively using LDCTPI examinations. The acquired volumetric imaging data were used for calculation, mapping and analysis by using a body tumor perfusion protocol in the CT perfusion software to measure 4 parameters: blood flow (BF), blood volume (BV), mean transit time (MTT), and the permeability surface (PS) area product. Statistical data analysis was then performed to distinguish the difference of the 4 parameter values among normal control, breast cancer and breast fibroadenoma cases. RESULTS: The mean perfusion values of 15 normal controls were as follows: BF, 20.03±4.08 mL/100 g/min; BV, 4.53±0.95 mL/100 g; MTT, 5.90±0.82 s; and PS, 9.25±1.18 mL/100 g/min. The mean perfusion values of 30 cancer patients were as follows: BF, 56.67±6.59 mL/100 g/min; BV, 5.82±0.68 mL/100 g; MTT, 6.01±0.82 s; and PS, 24.95±5.05 mL/100 g/min. The mean perfusion values of 20 patients with breast fibroadenoma were as follows: BF, 46.24±6.65 mL/100 g/min; BV, 5.07±0.73 mL/100 g; MTT, 7.51±0.62 s; and PS, 16.73±6.48 mL/100 g/min. Comparing the 3 groups, differences were all statistically significant for BF, BV, MTT and PS values (p < 0.05, respectively); The BF, BV, PS values were highest in group of cancer patients, while the MTT value was highest in group of patients diagnosed with breast fibroadenoma. CONCLUSION: Breast CT perfusion imaging is a promising functional imaging technology in breast cancer diagnosis, which can provide valuable quantitative imaging markers to assist evaluation of breast tumors.