A Four-Gene Panel in Rectal Swab Samples as a Biomarker for Colorectal Cancer Screening.

Background: The dysregulation of gene expression is one of the key molecular features of colorectal cancer (CRC) development. This study aimed to investigate whether such dysregulation is reflected in rectal swab specimens of CRC patients and to evaluate its potential as a non-invasive approach for screening.

Methods: We compared the expression level of 14 CRC-associated genes in tumor and adjacent non-tumor tissue of CRC patients and examined the correlation of their levels in tissue with paired rectal swab specimens.

High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients.

Background: Several studies have demonstrated that the molecular profile of normal tissue adjacent to the tumor (NAT) is prognostic for recurrence in patients with different cancers. This study investigated the clinical significance of CBX8 gene expression, a cancer stemness-related gene, in tumor and NAT tissue of colorectal cancer (CRC) patients.

Methods: The gene level of CBX8 in paired CRC and NAT specimens from 95 patients was determined by quantitative PCR.

CD26 Induces Colorectal Cancer Angiogenesis and Metastasis through CAV1/MMP1 Signaling.

CD26 has been reported as a marker for colorectal cancer stem cells endowed with tumor-initiating properties and capable of colorectal cancer (CRC) metastasis. In this study, we investigated the functional effect of CD26 on CRC angiogenesis and metastasis, and the potential underlying mechanism. The functional effects of CD26 overexpression or repression were determined by a wound healing experiment, and cell migration and invasion assays in vitro and in mouse models.

Small RNA Profiling of piRNAs in Colorectal Cancer Identifies Consistent Overexpression of That Correlates Clinically with an Aggressive Disease Phenotype.

Piwi-interacting RNAs (piRNAs) represent a novel class of small non-coding RNAs (ncRNAs) that have been shown to have a deregulated expression in several cancers, although their clinical significance in colorectal cancer (CRC) remains unclear. With an aim of delineating the piRNA distribution in CRC, we conducted a systematic discovery and validation of piRNAs within two clinical cohorts. In the discovery phase, we profiled tumor and adjacent normal tissues from 18 CRC patients by deep sequencing and identified a global piRNA downregulation in CRC.

Overexpression of Pin1 and rho signaling partners correlates with metastatic behavior and poor recurrence-free survival of hepatocellular carcinoma patients.

Background: Identification of molecular markers for early detection or prediction of metastasis is crucial for both management of HCC patient postoperative treatment and identify new therapeutic targets to inhibit HCC progression and metastasis. In the current study, we investigated the clinical correlation between Pin1, RhoA and RhoC and their association with HCC metastasis.

Methods: Using a randomized study design of primary HCC samples from 139 patients, we determined messenger RNA expression of Pin1, RhoA and RhoC and their prognostic value.

Suppression of Slit3 induces tumor proliferation and chemoresistance in hepatocellular carcinoma through activation of GSK3β/β-catenin pathway.

Background: It is essential to understand the mechanisms responsible for hepatocellular carcinoma (HCC) progression and chemoresistance in order to identify prognostic biomarkers as well as potential therapeutic avenues. Recent findings have shown that SLIT3 appears to function as a novel tumor suppressor gene in various types of cancers, yet its clinical correlation and role in HCC has not been understood clearly.

Methods: We determined the transcript levels of Slit3 in tumor and adjacent normal tissues within two cohorts (N = 40 and 25) of HCC patients, and correlated the gene expression with the clinicopathological data.

Emergence of CD26+ Cancer Stem Cells with Metastatic Properties in Colorectal Carcinogenesis.

Colorectal cancer results from genetic aberrations which accumulate over a long period of time, with malignant and metastatic properties acquired at a relatively late stage. A subpopulation of CD26+ colorectal cancer stem cells are known to be implicated in metastasis. We quantified CD26+ cancer cells in 11 primary tumor samples by flow cytometry, and showed that tumors having confirmed or suspected metastases harbored a relatively high CD26+ level in these samples.

Identification of microRNA 885-5p as a novel regulator of tumor metastasis by targeting CPEB2 in colorectal cancer.

Colorectal cancer is the third most common cancer in the world and liver is the most frequent site of distant metastasis with poor prognosis. The aim of this study is to investigate microRNAs leading to liver metastasis. We applied microarray analysis and quantitative PCR to identify and validate dysregulated miRNAs in liver metastases when compared to primary CRCs.

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.

Nine-year experience of doxorubicin-eluting beads chemoembolization for hepatocellular carcinoma.

Background: Chemoembolization with doxorubucin-eluting beads (DEB) has been used to treat hepatocellular carcinoma (HCC) since 2007. This study compared the efficacy and survival between transarterial chemoembolization (TACE) with DEB and conventional approach (cTACE) in HCC treatment.

Methods: This retrospective case-control study compared the overall survival and tumor response of HCC patients to cTACE (n=190) and DEB (n=143) by the reassessment of computed tomography and serum alpha-fetoprotein (AFP).

A preclinical study on the combination therapy of everolimus and transarterial chemoembolization in hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is commonly used for the treatment of locally advanced hepatocellular carcinoma (HCC) by its dual effects of chemotherapy and ischemic hypoxia. However, one of the side effects of TACE is the introduction of hypoxic condition, which in turn activates hypoxia-induced survival pathways and enhances VEGF-induced neovascularization by stabilizing HIF-1α expression. Herein, the preclinical therapeutic efficacy of the combined treatment of everolimus, a novel mTOR inhibitor and TACE for the treatment of HCC was investigated.

Post-operative plasma osteopontin predicts distant metastasis in human colorectal cancer.

Background: The overall prognosis of colorectal cancer (CRC) patients is unsatisfactory due to cancer metastasis after operation. This study aims to investigate the clinical significance of plasma osteopontin (OPN) levels as minimally invasive, predictive, and surrogate biomarkers for prognosis of CRC patients.

Methods: This randomized study design consists of pre-operative and post-operative plasma samples from a total of 79 patients.

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

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.

Preliminary efficacy, safety, pharmacokinetics, pharmacodynamics and quality of life study of pegylated recombinant human arginase 1 in patients with advanced hepatocellular carcinoma.

This study was designed to evaluate the efficacy, safety profile, pharmacokinetics, pharmacodynamics and quality of life of pegylated recombinant human arginase 1 (Peg-rhAgr1) in patients with advanced hepatocellular carcinoma (HCC). Patients were given weekly doses of Peg-rhAgr1 (1600 U/kg). Tumour response was assessed every 8 weeks using RECIST 1.

Advanced pancreatic cancer: flourishing novel approaches in the era of biological therapy.

The progress in the development of systemic treatment for advanced pancreatic cancer (APC) has been slow. The mainstream treatment remains using chemotherapy including gemcitabine, FOLFIRINOX, and nab-paclitaxel. Erlotinib is the only approved biological therapy with marginal benefit.

The clinicopathological significance of miR-133a in colorectal cancer.

This study determined the expression of microRNA-133a (MiR-133a) in colorectal cancer (CRC) and adjacent normal mucosa samples and evaluated its clinicopathological role in CRC. The expression of miR-133a in 125 pairs of tissue samples was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and correlated with patient's clinicopathological data by statistical analysis. Endogenous expression levels of several potential target genes were determined by qRT-PCR and correlated using Pearson's method.

Survivin depletion inhibits tumor growth and enhances chemosensitivity in hepatocellular carcinoma.

Survivin is a member of the inhibitor of apoptosis family, which has been suggested to be crucial in the control of cell division and inhibition of apoptosis. Expression of this protein has been observed in transformed cell lines and human tumor tissues, including those from colorectal cancer, but not in terminally differentiated adult tissues. Survivin mRNA expression has frequently been detected in hepatocellular carcinoma (HCC) and its protein expression has been demonstrated to be highly correlated with proliferation index rather than apoptotic index.

Plasma Bmi1 mRNA as a potential prognostic biomarker for distant metastasis in colorectal cancer patients.

Bmi1 is overexpressed in gastrointestinal cancers, including colorectal cancer (CRC); however, its role as a non-invasive biomarker in CRC has not been established. The aim of this study was to compare the plasma Bmi1 mRNA levels prior to and following curative resection of the primary tumor in CRC patients and to determine their association with the clinicopathological parameters. The plasma Bmi1 mRNA level was measured by quantitative polymerase chain reaction and expressed as cycle threshold value.

Prognostic significance of CD26 in patients with colorectal cancer.

Background: CD26, dipeptidyl peptidase IV, was discovered firstly as a membrane-associated peptidase on the surface of leukocyte. We previously demonstrated that a subpopulation of CD26+ cells were associated with the development of distant metastasis, enhanced invasiveness and chemoresistance in colorectal cancer (CRC). In order to understand the clinical impact of CD26, the expression was investigated in CRC patient's specimens.

The Enhanced metastatic potential of hepatocellular carcinoma (HCC) cells with sorafenib resistance.

Acquired resistance towards sorafenib treatment was found in HCC patients, which results in poor prognosis. To investigate the enhanced metastatic potential of sorafenib resistance cells, sorafenib-resistant (SorR) cell lines were established by long-term exposure of the HCC cells to the maximum tolerated dose of sorafenib. Cell proliferation assay and qPCR of ABC transporter genes (ABCC1-3) were first performed to confirm the resistance of cells.

Epigenetic regulation of pluripotent genes mediates stem cell features in human hepatocellular carcinoma and cancer cell lines.

Activation of the stem cell transcriptional circuitry is an important event in cancer development. Although cancer cells demonstrate a stem cell-like gene expression signature, the epigenetic regulation of pluripotency-associated genes in cancers remains poorly understood. In this study, we characterized the epigenetic regulation of the pluripotency-associated genes NANOG, OCT4, c-MYC, KLF4, and SOX2 in a variety of cancer cell lines and in primary tumor samples, and investigated the re-activation of pluripotency regulatory circuits in cancer progression.

Suppression of actopaxin impairs hepatocellular carcinoma metastasis through modulation of cell migration and invasion.

Unlabelled: Early reports suggested that actopaxin, a member of the focal adhesion proteins, regulates cell migration. Here we investigated whether actopaxin is involved in hepatocellular carcinoma (HCC) progression and metastasis. We examined actopaxin expression in human HCC samples using immunohistochemistry and western blotting.

Over-expression of miR-106b promotes cell migration and metastasis in hepatocellular carcinoma by activating epithelial-mesenchymal transition process.

Hepatocellular carcinoma (HCC) is one the the most fatal cancers worldwide. The poor prognosis of HCC is mainly due to the developement of distance metastasis. To investigate the mechanism of metastasis in HCC, an orthotopic HCC metastasis animal model was established.