MiR-2110 induced by chemically synthesized cinobufagin functions as a tumor-metastatic suppressor via targeting FGFR1 to reduce PTEN ubiquitination degradation in nasopharyngeal carcinoma.

Tumor cell metastasis is the key cause of death in patients with nasopharyngeal carcinoma (NPC). MiR-2110 was cloned and identified in Epstein-Barr virus (EBV)-positive NPC, but its role is unclear in NPC. In this study, we investigated the effect of miR-2110 on NPC metastasis and its related molecular basis. In addition, we also explored whether miR-2110 can be regulated by cinobufotalin (CB) and participate in the inhibition of CB on NPC metastasis. Bioinformatics, RT-PCR, and in situ hybridization were used to observe the expression of miR-2110 in NPC tissues and cells. Scratch, Boyden, and tail vein metastasis model of nude mouse were used to detect the effect of miR-2110 on NPC metastasis. Western blot, Co-IP, luciferase activity, colocalization of micro confocal and ubiquitination assays were used to identify the molecular mechanism of miR-2110 affecting NPC metastasis. Finally, miR-2110 induced by CB participates in CB-stimulated inhibition of NPC metastasis was explored. The data showed that increased miR-2110 significantly suppresses NPC cell migration, invasion, and metastasis. Suppressing miR-2110 markedly restored NPC cell migration and invasion. Mechanistically, miR-2110 directly targeted FGFR1 and reduced its protein expression. Decreased FGFR1 attenuated its recruitment of NEDD4, which downregulated NEDD4-induced phosphatase and tensin homolog (PTEN) ubiquitination and degradation and further increased PTEN protein stability, thereby inactivating PI3K/AKT-stimulated epithelial-mesenchymal transition signaling and ultimately suppressing NPC metastasis. Interestingly, CB, a potential new inhibitory drug for NPC metastasis, significantly induced miR-2110 expression by suppressing PI3K/AKT/c-Jun-mediated transcription inhibition. Suppression of miR-2110 significantly restored cell migration and invasion in CB-treated NPC cells. Finally, a clinical sample assay indicated that reduced miR-2110 was negatively correlated with NPC lymph node metastasis and positively related to NPC patient survival prognosis. In summary, miR-2110 is a metastatic suppressor involving in CB-induced suppression of NPC metastasis.

Effects of rTMS Treatment on Cognitive Impairment and Resting-State Brain Activity in Stroke Patients: A Randomized Clinical Trial.

Background: Repetitive transcranial magnetic stimulation (rTMS) has been employed for motor function rehabilitation for stroke patients, but its effects on post-stroke cognitive impairment (PSCI) remains controversial. Objective: To identify the effects of rTMS intervention on PSCI patients and its potential neural correlates to behavioral improvements. Methods: We recruited 34 PSCI patients for 20 sessions of 10 Hz rTMS or no-stim control treatments over the left dorsal lateral prefrontal cortex (DLPFC). Cognitive function was evaluated with the Montreal Cognitive Assessment Scale, Victoria Stroop Test, Rivermead Behavior Memory Test, and Activities of Daily Living (ADL) assessed with the Modified Barthel Index. 14 patients received functional MRI scan, a useful non-invasive technique of determining how structurally segregated and functionally specialized brain areas were interconnected, which was reflected by blood oxygenation level-dependent signals. The amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) were applied as the analytical approaches, which were used to measure the resting-state brain activity and functional connection. Results: rTMS improved cognitive functions and ADLs for PSCI patients relative to patients who received no-stim control treatment. The cognitive improvements correlated to increased ALFF of the left medial prefrontal cortex, and increased FC of right medial prefrontal cortex and right ventral anterior cingulate cortex. Conclusion: 10 Hz rTMS at DLPFC could improve cognitive function and quality of life for PSCI patients, which is associated with an altered frontal cortical activity. Clinical Registration: Chinese Clinical Trial Registry, ChiCTR-IPR-17011908, http://www.chictr.org.cn/index.aspx.

Synthesis and Activity Evaluation of Nasopharyngeal Carcinoma Inhibitors Based on 6-(Pyrimidin-4-yl)-1H-indazole.

Human nasopharyngeal carcinoma is a common head and neck malignancy with high incidence in Southeast Asia and Southern China. It is necessary to develop safe, effective and inexpensive anticancer agents to improve the therapeutics of patients with nasopharyngeal carcinoma. A series of small molecular compounds based on 6-(pyrimidin-4-yl)-1H-indazole were synthesized and evaluated for antiproliferative activities against human nasopharyngeal carcinoma cell lines SUNE1. Compounds 6b, 6c, 6e and 6l showed potent antiproliferative activities similar to positive control drug cisplatin in vitro with lower nephrotoxicity than it. N-[4-(1H-Indazol-6-yl)pyrimidin-2-yl]benzene-1,3-diamine (6l) was selected for further study. It was found that 6l induced mitochondria-mediated apoptosis and G2 /M phase arrest in SUNE1 cells. Furthermore, compound 6l at 10 mg/kg can suppress the growth of an implanted SUNE1 xenograft with a TGI% (tumor growth inhibition) value of 50 % and did not cause serious side effects in BALB/c nude mice. This study suggests that 6-(pyrimidin-4-yl)-1H-indazole derivatives are a series of small molecule compounds with anti-nasopharyngeal carcinoma activities.

Preoperative elevated plasma fibrinogen level predicts tumor recurrence and poor prognosis in patients with hepatocellular carcinoma.

BACKGROUND: Elevated plasma fibrinogen has been reported to be associated with poor prognosis in several cancers. The aim of present study was to investigate the prognostic value of preoperative plasma fibrinogen in hepatocellular carcinoma (HCC) patients. METHODS: Data were collected retrospectively from 302 HCC patients who received hepatectomy. The association between fibrinogen and clinicopathological characteristics was evaluated. Both univariate and multivariate analyses were performed to identify prognostic factors for disease-free survival (DFS) and overall survival (OS). And accordingly, the nomograms were constructed. RESULTS: Elevated plasma fibrinogen (>4 g/L) was correlated with larger tumor diameter, the presence of vascular invasion, lower MELD score, higher NLR, advanced Barcelona Clinic Liver Cancer stage and poor-moderate pathological differentiation. On multivariate analysis, the elevated plasma fibrinogen was found independently associated with poor DFS (HR =1.575, P=0.024) and OS (HR =2.051, P=0.025). And the nomograms including fibrinogen were constructed to predict DFS and OS for HCC patients. Both DFS and OS in patients with plasma fibrinogen >4 g/L were significantly lower than those with fibrinogen ≤4 g/L (1-, 3-, 5-year DFS: 34.2%, 19.5% and 0.0% vs. 60.4%, 34.2% and 30.2%; 1-, 3-, 5-year OS: 83.4%, 62.7% and 48.8% vs. 95.4%, 84.3% and 75.8%, both P<0.001). Besides, subgroup analyses also showed the prognostic values of fibrinogen in HCC patients with/without cirrhosis or high AFP levels, and in those with single tumor and BCLC 0-A stage. CONCLUSIONS: Preoperative elevated plasma fibrinogen was an independent prognostic factor associated with poor prognosis in HCC patients receiving liver resection.

Whole-lesion histogram analysis of the apparent diffusion coefficient: Evaluation of the correlation with subtypes of mucinous breast carcinoma.

PURPOSE: To evaluate the utility of the whole-lesion histogram apparent diffusion coefficient (ADC) for characterizing the heterogeneity of mucinous breast carcinoma (MBC) and to determine which ADC metrics may help to best differentiate subtypes of MBC. MATERIALS AND METHODS: This retrospective study involved 52 MBC patients, including 37 pure MBC (PMBC) and 15 mixed MBC (MMBC). The PMBC patients were subtyped into PMBC-A (20 cases) and PMBC-B (17 cases) groups. All patients underwent preoperative diffusion-weighted imaging (DWI) at 1.5T and the whole-lesion ADC assessments were generated. Histogram-derived ADC parameters were compared between PMBC vs. MMBC and PMBC-A vs. PMBC-B, and receiver operating characteristic (ROC) curve analysis was used to determine optimal histogram parameters for differentiating these groups. RESULTS: The PMBC group exhibited significantly higher ADC values for the mean (P = 0.004), 25th (P = 0.004), 50th (P = 0.004), 75th (P = 0.006), and 90th percentiles (P = 0.013) and skewness (P = 0.021) than did the MMBC group. The 25th percentile of ADC values achieved the highest area under the curve (AUC) (0.792), with a cutoff value of 1.345 × 10-3 mm2 /s, in distinguishing PMBC and MMBC. The PMBC-A group showed significantly higher ADC values for the mean (P = 0.049), 25th (P = 0.015), and 50th (P = 0.026) percentiles and skewness (P = 0.004) than did the PMBC-B group. The 25th percentile of the ADC cutoff value (1.476 × 10-3 mm2 /s) demonstrated the best AUC (0.837) among the ADC values for distinguishing PMBC-A and PMBC-B. CONCLUSION: Whole-lesion ADC histogram analysis enables comprehensive evaluation of an MBC in its entirety and differentiating subtypes of MBC. Thus, it may be a helpful and supportive tool for conventional MRI. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:391-400.

Short-Term Outcomes of Single-Incision Versus Conventional Laparoscopic Surgery for Colorectal Diseases: Meta-Analysis of Randomized and Prospective Evidence.

BACKGROUND: Conventional laparoscopic surgery (CLS) has been established as an alternative to open surgery for colorectal diseases (CRDs); simultaneously, single-incision laparoscopic surgery (SILS) is gaining popularity. OBJECTIVE: The aim of this study was to compare the short-term efficacy and safety of SILS with CLS for CRDs. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched for relevant randomized and prospective studies. Reference lists of relevant articles and reviews, conference proceedings, and ongoing trial databases were also screened. Outcome measures included surgical parameters, postsurgical recovery, pain, and adverse events. Meta-analysis was conducted where appropriate, comparing items using weighted mean differences (WMDs) and risk ratios (RRs) according to data type. RESULTS: A total of nine prospective (three randomized and six non-randomized) researches published from 2011 to 2015 were identified. The overall pooled results showed compared to CLS, SILS was associated with fewer blood transfusions, shorter incision length, and slighter postoperative pain, but more extra ports. All the other parameters were comparable. Randomized evidence supported SILS was associated with less blood loss, and shorter hospital stay, but longer operative time. For only colectomy cases, SILS was associated with more conversions to open surgery. SILS was associated with longer surgical time for Easterners, but not for Westerners. The detected differences were clinically insignificant. CONCLUSIONS: The results based on randomized and prospective evidence provide convincing support for the clinical similarity that SILS is basically as applicable, effective, and safe as CLS when dealing with colorectal lesions, but not for superiority.

[Multiphasic spiral CT scanning features in 100 patients with small renal cell carcinoma].

OBJECTIVE: To investigate the role of multiphasic spiral computed tomography (SCT) in the differential diagnosis of small renal cell carcinoma. METHODS: The data of 100 patients with small renal cell carcinoma (< or = 3.0 cm) proved by pathology were retrospectively reviewed in order to analyze the features of SCT during plain, corticomedullary and excretory phases. There were 83 males and 17 females, with a mean age of 54. 3 years ranging from 9 to 81 years. RESULTS: There were 38 tumor masses in the left kidney and 62 in the right one. They were 1.0-3.0 cm (mean, 2.5 cm) in the greatest dimension. According to the 2004 WHO histological classification criteria for the tumors of the kidney. Seventy-six patients had clear cell renal cell carcinoma, 4 multilocular clear cell renal cell carcinomas, 9 papillary renal cell carcinoma, 4 chromophobe renal cell carcinomas and 7 unclassified renal cell carcinomas. Clear cell renal cell carcinoma exhibited rich blood supply and inhomogeneous density due to hemorrhage, necrosis or cystic degeneration. Multilocular clear cell renal cell carcinoma presented as a multilocular cystic mass with thin wall and septa, instead of an expansile nodule. Papillary renal cell carcinoma showed inhomogeneous density and hypovascular distribution. Chromophobe renal cell carcinoma was relatively homogeneous and hypovascular. Compared with clear cell renal cell carcinoma, unclassified renal cell carcinoma showed inhomogeneous density and hypervascular distribution with more invading growth features than the other subtypes. CONCLUSION: Commonly encountered subtypes of the small renal cell carcinoma exhibit their own specific features in multiphasic spiral CT, which may be helpful in differential diagnosis, but each subtype should be differentiated from the renal oncocytoma, cystic nephroma, complex renal cyst, renal angiomyolipoma with minimal fat and renal infiltrating urothelial carcinoma.