The diagnostic significance of CDH17-positive circulating tumor cells in patients with colorectal cancer.

Background: Colorectal cancer (CRC) is the second leading cause of cancer deaths in Hong Kong. We tested the hypothesis that circulating tumor cell (CTC) analysis by ARB101 antibody could be used as a tool for CRC detection, progression, and therapy response.

Research Methods: ARB101 antibody was used for investigation of CDH17 expression in formalin-fixed, paraffin-embedded (FFPE) tissue sections and circulating tumor cells (CTCs) of CRC patients.

Clinical correlation of cadherin-17 marker with advanced tumor stages and poor prognosis of cholangiocarcinoma.

Background And Objectives: In this retrospective study, we examined the CA17 tissue expression and analyzed its clinical significance in cholangiocarcinoma (CCA).

Materials And Methods: Immunohistochemistry was performed to assess CA17 expression on tissue microarrays in a training cohort enrolling 120 CCA patients and a validation cohort comprising 60 CCA patients. Image pro plus was applied to score the staining intensity and expression level of CA17 marker.

Integrin α2β1 inhibits MST1 kinase phosphorylation and activates Yes-associated protein oncogenic signaling in hepatocellular carcinoma.

The Hippo pathway regulates the down-stream target Yes-associated protein (YAP) to maintain organ homeostasis, which is commonly inactivated in many types of cancers. However, how cell adhesion dysregulates the Hippo pathway activating YAP oncogene in hepatocellular carcinoma (HCC) remains unclear. Our findings demonstrate that α2β1 integrin (but not other β1 integrins) expressed in HCC cells, after binding to collagen extracellular matrix, could inhibit MST1 kinase phosphorylation and activate YAP pro-oncogenic activities.

Diverse modes of genomic alteration in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a heterogeneous disease with high mortality rate. Recent genomic studies have identified TP53, AXIN1, and CTNNB1 as the most frequently mutated genes. Lower frequency mutations have been reported in ARID1A, ARID2 and JAK1.

Inhibition of STAT3 dimerization and acetylation by garcinol suppresses the growth of human hepatocellular carcinoma in vitro and in vivo.

Background: Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been linked with proliferation, survival, invasion and angiogenesis of a variety of human cancer cells, including hepatocellular carcinoma (HCC). Thus, novel agents that can suppress STAT3 activation have potential for both prevention and treatment of HCC. Here we report, garcinol, a polyisoprenylated benzophenone, could suppress STAT3 activation in HCC cell lines and in xenografted tumor of HCC in nude mice model.

miR-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma.

In contrast to normal differentiated cells that depend on mitochondrial oxidative phosphorylation for energy production, cancer cells have evolved to utilize aerobic glycolysis (Warburg's effect), with benefit of providing intermediates for biomass production. MicroRNA-122 (miR-122) is highly expressed in normal liver tissue regulating a wide variety of biological processes including cellular metabolism, but is reduced in hepatocellular carcinoma (HCC). Overexpression of miR-122 was shown to inhibit cancer cell proliferation, metastasis, and increase chemosensitivity, but its functions in cancer metabolism remains unknown.

Oncofetal gene SALL4 in aggressive hepatocellular carcinoma.

Background: Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment.

Circulating markers for prognosis of hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is a lethal liver malignancy with an exceptionally high incidence in Asia and Africa. The number of new cases in America and Europe is rapidly increasing, making HCC a worldwide health problem. Patients with early HCC can be treated by potentially curative interventions such as tumor resection, liver transplantation, and radiofrequency ablation, but unfortunately a considerable portion of them would develop tumor recurrence, which in many cases cannot be detected early.

Discovery of lamin B1 and vimentin as circulating biomarkers for early hepatocellular carcinoma.

The recent advancements in proteomic technologies have reconstituted our research strategies over different type of liver diseases including hepatocellular carcinoma (HCC). Combined analyses on HCC proteome and clinicopathological data of patients have allowed identification of many promising biomarkers that can be further developed into noninvasive diagnostic assays for cancer surveillance. Capitalizing our established proteomic platform primarily based on two-dimensional polyacrylamide gel electrophoresis (2DE) and MALDI-TOF/TOF mass spectrometry, our groups have identified lamin B1 (LMNB1) and vimentin (VIM) as promising biomarkers for detection of early HCC.

Regulators of mammalian Hippo pathway in cancer.

Hippo pathway, originally discovered in Drosophila, is responsible for organ size control. The pathway is conserved in mammals and has a significant role in restraining cancer development. Regulating the Hippo pathway thus represents a potential therapeutic approach to treat cancer, which however requires deep understanding of the targeted pathway.

Stabilization of ferrochelatase via lysine residues on the carboxyl terminal extension.

There are accumulating evidences suggesting that ferrochelatase is involved in different cellular functions other than heme biosynthesis. The carboxyl-terminal extension of the enzyme may play a role associated with its stability and signaling process. Two transcript variants encoding different isoforms have been found for this ferrochelatase-coding gene.

Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study.

Objective: Serum α-fetoprotein (AFP) is the most commonly used biomarker for screening hepatocellular carcinoma (HCC) but fails to detect about half of the patients. Thus, we investigated if circulating microRNAs (miRNAs) could outperform AFP for HCC detection.

Design: A retrospective cohort study.

Celastrol suppresses growth and induces apoptosis of human hepatocellular carcinoma through the modulation of STAT3/JAK2 signaling cascade in vitro and in vivo.

Cumulative evidences(s) have established that the constitutive activation of STAT3 plays a pivotal role in the proliferation, survival, metastasis, and angiogenesis and thus can contribute directly to the pathogenesis of hepatocellular carcinoma (HCC). Thus, novel agents that can inhibit STAT3 activation have potential for both prevention and treatment of HCCs. The effect of celastrol on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was investigated.

Tripterygium wilfordii bioactive compounds as anticancer and anti-inflammatory agents.

1. Bioactive compounds from medicinal plants with anticancer and anti-inflammatory effects have become key resources in drug discovery fields for the treatment of various malignancies and immunological disorders. 2.

Global regulation on microRNA in hepatitis B virus-associated hepatocellular carcinoma.

Recent work has revealed the causative links between deregulation of microRNAs (miRNAs) and cancer development. In hepatocellular carcinoma (HCC), aberrant expression of miRNAs has been observed, but the molecular mechanisms that contribute to such changes remains to be elucidated. Here, we reported the analysis of miRNA expression in 94 pairs of tumor and adjacent nontumor tissues from HBV-associated HCC in Chinese patients.

microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma.

Tumorigenesis involves multistep genetic alterations. To elucidate the microRNA (miRNA)-gene interaction network in carcinogenesis, we examined their genome-wide expression profiles in 96 pairs of tumor/non-tumor tissues from hepatocellular carcinoma (HCC). Comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-122 is under-expressed in HCC and that increased expression of miR-122 seed-matched genes leads to a loss of mitochondrial metabolic function.

HNF1α and CDX2 transcriptional factors bind to cadherin-17 (CDH17) gene promoter and modulate its expression in hepatocellular carcinoma.

Cadherin-17 (CDH17) belongs to the cell adhesion cadherin family with a prominent role in tumorigenesis. It is highly expressed in human hepatocellular carcinoma (HCC) and is proposed to be a biomarker and therapeutic molecule for liver malignancy. The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC.

Prophylactic uses of integrin CD18-betaA peptide in a murine polymicrobial peritonitis model.

Aim: To evaluate the prophylactic properties of integrin CD18-betaA peptide in a murine model of abdominal polymicrobial peritonitis and sepsis.

Methods: Bacterial sepsis was induced in Institute of Cancer Research (ICR) mice by cecal ligation and puncture (CLP) surgery. Inflicted mice were then injected with either sterile saline or CD18-betaA peptide intraperitoneally at 2 h after surgery, and were sacrificed at 12 and 24 h after surgery.

Enhanced detection of early hepatocellular carcinoma by serum SELDI-TOF proteomic signature combined with alpha-fetoprotein marker.

Background: Biomarkers for accurate diagnosis of early hepatocellular carcinoma (HCC) are limited in number and clinical validation. We applied SELDI-TOF-MS ProteinChip technology to identify serum profile for distinguishing HCC and liver cirrhosis (LC) and to compare the accuracy of SELDI-TOF-MS profile and alpha-fetoprotein (AFP) level in HCC diagnosis.

Patients And Methods: Serum samples were obtained from 120 HCC and 120 LC patients for biomarker discovery and validation studies.

Endotoxin-neutralizing peptides as gram-negative sepsis therapeutics.

Bacterial endotoxin [e.g. lipopolysaccharide (LPS)] can trigger systemic hyper-inflammatory that subsequently leads to multiple organ failure and lethality (gram-negative sepsis).

Id-1 induces proteasome-dependent degradation of the HBX protein.

Id-1 is a member of the HLH protein family that regulates a wide range of cellular processes such as cell proliferation, apoptosis, senescence and overexpression of Id-1 was recently suggested to play roles in the development and progression of different cancers. Previously, Id-1 was shown to physically interact with the viral protein E1A. Meanwhile, Id-1 expression was found to be regulated by several of the virus-encoded proteins, suggesting that Id-1 may be a common cellular target of the viral proteins.

Laparoscopic surgery induced interleukin-6 levels in serum and gut mucosa: implications of peritoneum integrity and gas factors.

Background: The peritoneum serves as an integral part of host immunity, and the homeostasis of intraperitoneal environment is held to be beneficial for patient recovery after abdominal surgery. How minimal invasive access to the abdomen by laparoscopy and incisions would alter the intraperitoneal immune response is not fully defined. This study examined the levels of IL-6 in serum and gut mucosa following laparoscopic surgery with reference to the peritoneum integrity and gas factors.

Immunochemical characterization of the functional constituents of Tripterygium wilfordii contributing to its anti-inflammatory property.

1. Tripterygium wilfordii (TW) contains bioactive compounds that possess immunosuppressive properties. These compounds are considered to be potential drugs in the treatment of acute graft rejections.

Traditional Chinese herbal medicines for treatment of liver fibrosis and cancer: from laboratory discovery to clinical evaluation.

Liver disease afflicts over 10% of the world population. This includes chronic hepatitis, alcoholic steatosis, fibrosis, cirrhosis and hepatocellular carcinoma (HCC), which are the most health-threatening conditions drawing considerable attention from medical professionals and scientists. Patients with alcoholism or viral hepatitis are much more likely to have liver cell damage and cirrhosis, and some may eventually develop HCC, which is unfortunately, and very often, a fatal malignancy without cure.

Characterization of two novel LPS-binding sites in leukocyte integrin betaA domain.

Lipopolysaccharide (LPS), a bacterial endotoxin, triggers deleterious systemic inflammatory responses when released into blood circulation, causing organ dysfunction and death. In response to LPS stimulation, CD14 and toll-like receptor (TLR)-4 elicit inflammatory signaling cascades. Although leukocyte integrins (CD11b/CD18 and CD11c/CD18) were reported to bind LPS and induce NF-kappaB translocation, the evidence on such epitope location remains elusive.