Characterization of cell cycle phase-based microRNAs in pluripotency and differentiation

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Emergence of CD26+ cancer stem cells with metastatic properties in colorectal carcinogenesis

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Preclinical analysis of the anti-tumor and anti-metastatic effects of Raf265 on colon cancer cells and CD26(+) cancer stem cells in colorectal carcinoma

© 2015 Chow et al.Background: In colorectal carcinoma (CRC), activation of the Raf/MEK/ERK signaling pathway is commonly observed. In addition, the commonly used 5FU-based chemotherapy in patients with metastatic CRC was found to enrich a subpopulation of CD26+ cancer stem cells (CSCs). As activation of the Raf/MEK/ERK signaling pathway was also found in the CD26+ CSCs and therefore, we hypothesized that an ATP-competitive pan-Raf inhibitor, Raf265, is effective in eliminating the cancer cells and the CD26+ CSCs in CRC patients. Methods: HT29 and HCT116 cells were treated with various concentrations of Raf265 to study the anti-proliferative and apoptotic effects of Raf265. Anti-tumor effect was also demonstrated using a xenograft model. Cells were also treated with Raf265 in combination with 5FU to demonstrate the anti-migratory and invasive effects by targeting on the CD26+ CSCs and the anti-metastatic effect of the combined treatment was shown in an orthotopic CRC model. Results: Raf265 was found to be highly effective in inhibiting cell proliferation and tumor growth through the inhibition of the RAF/MEK/ERK signaling pathway. In addition, anti-migratory and invasive effect was found with Raf265 treatment in combination with 5FU by targeting on the CD26+ cells. Finally, the anti-tumor and anti-metastatic effect of Raf265 in combination with 5FU was also demonstrated. Conclusions: This preclinical study demonstrates the anti-tumor and anti-metastatic activity of Raf265 in CRC, providing the basis for exploiting its potential use and combination therapy with 5FU in the clinical treatment of CRC.published_or_final_versio

Identification of serum miR-139-3p as a non-invasive biomarker for colorectal cancer

Aberrant levels of circulating microRNAs are potential biomarkers for the early detection of colorectal cancer. The aim of this study was to study miR-139-3p and miR-622 in serum as a non-invasive biomarker for colorectal cancer diagnosis. We applied quantitative polymerase chain reaction to determine the levels of miR-139-3p and miR-622 in 42 pairs of tumor and adjacent non-tumor tissues, and in serum samples of 117 patients and 90 control subjects. Our results showed that miR-139-3p was silenced whereas miR-622 was overexpressed in colorectal cancer. Similarly, serum miR-139-3p level was significantly lower in colorectal cancer patients than in control subjects whereas miR-622 was more frequently detectable in patients. ROC analysis showed that AUC of miR-139-3p was 0.9935, with a sensitivity of 96.6% and specificity of 97.8%. Serum miR-139-3p level showed high sensitivity and specificity for both early and late stage CRCs and proximal and distal CRCs. Detectable serum miR-622 showed a sensitivity of 87.5% and specificity of 63.5% for discriminating CRC patients, but the sensitivity dropped for late stage patients (72.7%). We also included analyses of the blood CEA level for comparing the diagnostic performance of these blood-based biomarkers. The median level in CRC patients (3.6 ng/ml) was significantly higher than that in control (1.8 ng/ml). The AUC value of CEA in diagnosing CRC patients was 0.7515. CEA showed a positive correlation with tumor stage and age of patients and its level was higher in male. Collectively, serum miR-139-3p has strong potential as a promising non-invasive biomarker in colorectal cancer detection.published_or_final_versio

An evaluation of a pilot counselling model in Hong Kong for individuals with mild-to-moderate psychological issues

Title on author's file: An evaluation of the effectiveness of a pilot 3-session counselling model with individuals with mild and moderate psychological issues in Hong Kong202305 bcwwAccepted ManuscriptSelf-fundedPublishe

The low-molecular-weight heparin, nadroparin, inhibits tumour angiogenesis in a rodent dorsal skinfold chamber model

BACKGROUND: Recently, low-molecular-weight heparins (LMWHs) were found to confer a survival advantage in cancer patients. The mechanism underlying this observation is unclear, but may involve inhibition of tumour angiogenesis. We aimed to examine the effects of nadroparin on tumour angiogenesis using a dorsal skinfold window chamber model in the Syrian hamster. METHODS: AMel-3 and HAP-T1 tumours were grown in donor animals and fragments implanted in the window chambers. Animals (N=46) were treated with 200 IU of nadroparin or saline for 10 days. Repeated intravital fluorescence microscopy was performed to calculate functional microcirculatory parameters: number (N) and length (L) of microvessels, vascular area fraction (AF), and red blood cell velocity (V). Microvessel density (MVD), fractal dimension, and pericyte coverage were assessed histologically. RESULTS: Active angiogenesis was observed in control animals, resulting in a significant increase in N, L, and AF. In nadroparin-treated animals, however, N and L did not increase whereas AF decreased significantly. Both groups showed an initial increase in V, but nadroparin treatment resulted in an earlier decrease in red blood cell velocity over time. Compared with control animals, nadroparin-treated animals showed a significantly lower MVD and fractal dimension but significantly higher pericyte coverage index (PCI). CONCLUSIONS: Taken together, these results suggest that the LMWH nadroparin inhibits tumour angiogenesis and results in microvessel normalisation