MicroRNA-30a Inhibits Colorectal Cancer Metastasis Through Down-Regulation of Type I Insulin-Like Growth Factor Receptor.

BACKGROUND: miR-30a expression is down-regulated and regulates tumor suppressors in various cancers. AIM: We investigated the mechanisms underlying the biological role of miR-30a in CRC. METHODS: MicroRNA, mRNA, and protein expression were analyzed by quantitative real-time PCR and Western blot. The migration and invasion abilities of CRC were determined by wound healing assay, and trans-well migration and invasion. A luciferase reporter assay was used to confirm the targets of miR-30a. RESULTS: miR-30a expression was significantly down-regulated in CRC tissues and in CRC tissue with lymph node metastasis compared to CRC tissue without metastasis. Overexpression of miR-30a suppressed migration and invasion through insulin-like growth factor 1 receptor (IGF1R) in CRC cells. miR-30a suppresses IGF1R protein expression and inhibits ß-catenin or p-AKT and increases E-cadherin expression. The IGF1R expression level is also up-regulated in CRC tumors and inversely correlated with miR-30a in CRC specimens. CONCLUSIONS: miR-30a functions as a tumor-suppressive miRNA, which may provide a therapeutic strategy for metastasis of CRC.

Reliability of tumour grade 1 and endometrioid cell type on preoperative endometrial biopsy.

The aim of this study was to evaluate the reliability of using tumour grade and cell type on preoperative endometrial biopsy for the selection of patients for conservative hormone treatment. We retrospectively reviewed results of 643 patients with endometrial carcinoma for tumour grade and 817 for tumour cell type who underwent endometrial biopsy followed by surgery. Of the 357 patients with a grade 1 tumour on preoperative endometrial biopsy, 58 (16.2%) were upgraded based on a final pathology report from hysterectomy specimens. For grade 1, the preoperative endometrial biopsy showed a sensitivity of 80.4%, a specificity of 78.6%, a positive predictive value (PPV) of 83.8% and a negative predictive value (NPV) of 74.5%. Of the 672 patients with the endometrioid cell type on preoperative biopsy, 46 (5.6%) showed a different cell type on final pathology. For the endometrioid cell type, preoperative endometrial biopsy had a sensitivity of 91.3%, a specificity of 64.9%, a PPV of 93.2% and an NPV of 58.6%. This weak predictive value should be considered when selecting patients for conservative hormone treatment.

Anaemia is independently associated with mortality in patients with hepatocellular carcinoma.

BACKGROUND: Anaemia is frequent in patients with cancer and/or liver cirrhosis and is associated with impaired quality of life. Here, we investigated the impact of anaemia on overall survival (OS) and clinical characteristics in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: HCC patients treated between 1992 and 2018 at the Medical University of Vienna were retrospectively analysed. Anaemia was defined as haemoglobin level <13 g/dl in men and <12 g/dl in women. RESULTS: Of 1262 assessable patients, 555 (44.0%) had anaemia. The main aetiologies of HCC were alcohol-related liver disease (n = 502; 39.8%) and chronic hepatitis C (n = 375; 29.7%). Anaemia was significantly associated with impaired liver function, portal hypertension, more advanced Barcelona Clinic Liver Cancer stage and elevated C-reactive protein (CRP). In univariable analysis, anaemia was significantly associated with shorter median OS [9.5 months, 95% confidence interval (95% CI) 7.3-11.6 months] versus patients without anaemia (21.5 months, 95% CI 18.3-24.7 months) (P < 0.001). In multivariable analysis adjusted for age, Model for End-stage Liver Disease, number of tumour nodules, size of the largest nodule, macrovascular invasion, extrahepatic spread, first treatment line, alpha-fetoprotein and CRP, anaemia remained an independent predictor of mortality (adjusted hazard ratio 1.23, 95% CI 1.06-1.43, P = 0.006). CONCLUSIONS: Anaemia was significantly associated with mortality in HCC patients, independent of established liver- and tumour-related prognostic factors. Whether adequate management of anaemia can improve outcome of HCC patients needs further evaluation.

MicroRNA-30a-5p (miR-30a) regulates cell motility and EMT by directly targeting oncogenic TM4SF1 in colorectal cancer.

PURPOSE: Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide, and many oncogenes and tumor suppressor genes are involved in CRC. MicroRNAs (miRNAs) are small non-coding RNAs that can negatively regulate gene expression. Previous studies have revealed that miRNAs regulate the development and progression of many cancers. In this study, we investigated the role of microRNA-30a-5p (miR-30a) in CRC and its unknown mechanisms. METHODS: qRT-PCR was used to detect miR-30a and TM4SF1 mRNA expression in CRC specimens and cell lines. CRC cell migration and invasion were assessed after transfection with miR-30a or TM4SF1 using wound healing and trans-well migration and invasion assays. Transmembrane-4-L-six-family protein (TM4SF1) was validated as a target of miR-30a in CRC through luciferase reporter assay and bioinformatics algorithms. Moreover, two EMT regulators, E-cadherin and VEGF, were also identified using Western blotting and immunohistochemistry. RESULTS: We found that miR-30a was down-regulated in CRC tumor tissues and cell lines, and miR-30a was inversely associated with advanced stage and lymph node metastatic status compared with normal tissues. miR-30a decreased migration and invasion in CRC cell lines, and miR-30a overexpression not only down-regulated TM4SF1 mRNA and protein expression, but also inhibited the expression of VEGF and enhanced expression of E-cadherin. We also showed that TM4SF1 was up-regulated in CRC tumor specimens compared with adjacent normal tissues, and TM4SF1 expression was significantly associated with advanced stage and lymph node status compared with adjacent normal tissues. CONCLUSIONS: These results suggest that miR-30a is an important regulator of TM4SF1, VEGF, and E-cadherin for CRC lymph node metastasis, a potential new therapeutic target in CRC.

Galactosylated chitosan-graft-dextran as hepatocyte-targeting DNA carrier.

Lactobionic acid bearing galactose group was coupled with chitosan for liver specificity, and dextran was grafted to galactosylated chitosan (GC) for stability in water. Compared to the GC/DNA complex, the stability of the galactosylated chitosan-graft-dextran (GCD)/DNA complex could be enhanced. The particle size of the GCD/DNA complexes decreased as the charge ratio of GCD to DNA increased. Conformational change of DNA did not occur after complex formation with GCD compared with the conformation of DNA itself. The GCD/DNA complexes were only transfected into Chang liver cells and that of Hep G2 having asialoglycoprotein receptors (ASGR), indicative of specific interaction of ASGRs on cells and galactose ligands on chitosan.

Predicting sun spots using a layered perceptron neural network.

Interest in neural networks has expanded rapidly in recent years. Selecting the best structure for a given task, however, remains a critical issue in neural-network design. Although the performance of a network clearly depends on its structure, the procedure for selecting the optimal structure has not been thoroughly investigated, it is well known that the number of hidden units must be sufficient to discriminate each observation correctly. A large number of hidden units requires extensive computational time for training and often times prediction results may not be as accurate as expected. This study attempts to apply the principal component analysis (PCA) to determine the structure of a multilayered neural network for time series forecasting problems. The main focus is to determine the number of hidden units for a multilayered feedforward network. One empirical experiment with sunspot data is used to demonstrate the usefulness of the proposed approach.

Dextrose affects gravitational spread of epidural anesthesia.

Chloroprocaine, 0.5 per cent, with physiologic saline solution, has a specific gravity of 1.007 and a osmolarity of 283 mOsm/l, which increase to a specific gravity of 1.025 and an osmolarity of 542 mOsm/l when chloroprocaine is prepared in dextrose, 5 per cent. Chloroprocaine, 2.7 per cent, shows similar increases in specific gravity and osmolarity with dextrose 5 per cent. The highest sensory anesthesia level attained in pregnant patients following epidural injection of 10 ml of each of these solutions was determined. Chloroprocaine in dextrose, 5 per cent, produced a significant lowering of the highest sensory anesthesia level attained, compared with solutions to which dextrose was not added.