Wan-Chi Tsai

Value of narrow band imaging endoscopy in early mucosal head and neck cancer

The purpose of this study was to show the investigated prevalence rate of brownish spots of early cancer under narrow band imaging (NBI) in different sites/types of the epithelium.

Cyclooxygenase-2 is involved in S100A2-mediated tumor suppression in squamous cell carcinoma.

S100A2 is considered a putative tumor suppressor due to its loss or down-regulation in several cancer types. However, no mechanism has been described for the tumor suppressor role of S100A2. In this study, ectopic expression of S100A2 in the human malignant squamous cell carcinoma cell line KB resulted in a significant inhibition of proliferation, migration, and invasion. Moreover, S100A2 significantly reduced the number of colonies (≥0.5 mm) formed in semisolid agar and decreased tumor growth and burden in nude mice. cDNA microarray analysis was used to compare mRNA expression profiles of vector- and S100A2-expressing isogenic cells. Among the genes deregulated by S100A2, the expression of cyclooxygenase-2 (COX-2) mRNA was significantly suppressed by S100A2 (2.4-fold). Western blot analysis confirmed that S100A2 reduced the expression of COX-2 protein in stably and transiently transfected KB and RPMI-2650 cells. COX-2 is frequently overexpressed in various types of cancer and plays an important role in tumor progression. Partial restoration of COX-2 expression attenuated the antitumor effect of S100A2 both in vitro and in vivo. Although the interplay between S100A2 and COX-2 remains to be clarified, these findings first showed a potent antitumor role of S100A2 in squamous cell carcinoma partly via reduced expression of COX-2. (Mol Cancer Res 2006;4(8):539–47)

Methylantcinate A induces tumor specific growth inhibition in oral cancer cells via Bax-mediated mitochondrial apoptotic pathway

An ergostane type triterpenoid methylantcinate A (MAA) isolated from the fruiting bodies of Antrodia camphorata inhibited the growth of oral cancer cell lines OEC-M1 and OC-2 in a dose-dependent manner, without cytotoxic to normal oral gingival fibroblast cells. The major mechanism of growth inhibition was apoptosis induction, as shown by flow cytometric analysis of annexin V-FITC and propidium iodide staining, caspase-3 activation and DNA fragmentation. The increased expression of pro-apoptotic Bax, poly-(ADP-ribose) polymerase cleavage, and activated caspase-3 and decreased expression of anti-apoptotic Bcl-2 and Bcl-xL were also observed. These results provide the first evidence that the anti-oral cancer effects of MAA may involve a mechanism through the mitochondrial dependent pathway. Thus, results reported here may offer further impulse to the development of MAA analogues as potential chemotherapeutic targets for oral cancer complications.

Methyl Antcinate A Suppresses the Population of Cancer Stem-Like Cells in MCF7 Human Breast Cancer Cell Line

Methyl antcinate A (MAA) is an ergostane-type triterpenoid extracted from the fruiting bodies of Antrodia camphorate that has been reported to be a cytotoxic agent towards some types of cancer cells, such as oral cancer and liver cancer. Cancer stem cells (CSCs) are a particular population within cancer cells which are responsible for tumor initiation, drug resistance and metastasis and targeting CSCs is an emerging area in cancer therapy. In this study, we examine the effect of MAA on cancer stem-like cells in the MCF7 human breast cancer cell line. Although MAA displayed very low cytotoxic effect towards MCF7 under normal culture conditions, it did show good inhibitory effects on the self-renewal capability which was examined by mammosphere culture including primary and secondary sphere. MAA also inhibited cell migration ability of MCF7 sphere cells. By western blot analysis, MAA was shown to suppress the expression of heat shock protein 27 and increase the expression of IκBα and p53. In conclusion, our data demonstrate that MAA has anti-CSC activity and is worthy of future development of potent anticancer agents.

Adsorption characteristics of copper(II) onto non-crosslinked and cross-linked chitosan immobilized on sand

Abstract In this study, Cu(II) removal using non-crosslinked and cross-linked chitosan-coated sand (CCS) from aqueous solution was investigated. To improve the mechanical and chemical stability, chitosan was coated onto sand (CCS) and cross-linked using epichlorohydrin (ECH) and ethylene glycol diglycidyl ether (EGDE). The effect of pH (2.0–5.0) on the adsorption capacity was examined. The maximum adsorption capacity of CCS, CCS–ECH, and CCS–EGDE occurred at an initial pH of 5.0, 4.0, and 5.0, respectively. The kinetic experimental data agreed well with pseudo-second order equation (R 2  > 0.988), which implies that chemisorption is the rate controlling step. Langmuir, Freundlich and Dubinin–Radushkevich were used to analyze the equilibrium data, where the Langmuir model provided the best fit for the isotherm data obtained using CCS, CCS–ECH, and CCS–EDGE (R 2  > 0.990). Adsorption-desorption was carried out using HCl solution (pH 1.0 and 3.0) and tap water (pH 7.0), where HCl solution (pH 1.0) provided t...

Ovatodiolide of Anisomeles indica Exerts the Anticancer Potential on Pancreatic Cancer Cell Lines through STAT3 and NF-κB Regulation

Pancreatic cancer is the eighth leading cause of cancer death worldwide. Patients with pancreatic cancer are normally diagnosed at an advanced stage and present poor survival rate. Ovatodiolide (OV), a bioactive macrocyclic diterpenoid isolated from Anisomeles indica, showed cytotoxicity effects in pancreatic cancer cells by inhibiting cell proliferation and inducing apoptosis. Moreover, not only were cell adhesion and invasion markedly suppressed in a dose-dependent manner, but the mRNA expression of matrix metalloproteinase-9 (MMP-9) and focal adhesion kinase (FAK) was also significantly decreased. Western blot analysis indicated that OV potently suppressed the phosphorylation of STAT-3 and its upstream kinase including ERK1/2, P38, and AKT Ser473. Meanwhile, OV inactivated the nuclear factor kappa B (NF-κB) by inhibiting IκB kinase (IKK α/β) activation and the subsequent suppression of inhibitor of kappa B (IκB) phosphorylation. These results demonstrated that OV could potentially inhibit Mia-PaCa2 cancer cells proliferation and induce apoptosis through modulation of NF-κB and STAT3 pathway. Moreover, OV suppressed cell invasiveness and interfered with cell-matrix adhesion in Mia-PaCa2 cancer cells by reducing MMP-9 and FAK transcription through suppressing NF-κB and STAT3 pathway. Taken together, our findings reveal a new therapeutic and antimetastatic potential of ovatodiolide for pancreatic cancer remedy.

Predicting the early invasiveness of nasopharyngeal mucosal neoplasia after radiotherapy by narrow‐band imaging: A pilot study

This study evaluated the correlation between the histologic findings of nasopharyngeal mucosal neoplasias after radiotherapy and narrow‐band imaging (NBI) endoscopic findings.

Lack of modulatory function of coding nucleotide polymorphism S100A2_185G>A in oral squamous cell carcinoma.

OBJECTIVE S100A2, a Ca(2+) -binding protein with two EF-hands, is a tumor suppressor in oral cancer. Helix III flanking the C-terminal EF-hand is implicated to participate in the interaction of S100A2 and its target(s). The aim of this study was to examine if the coding sequence polymorphism S100A2_185G>A, leading to the peptide 62 substitution of asparagine (AAC, A allele) for serine (AGC, G allele) in helix III, had modulation effects on S100A-mediated tumor suppression. SUBJECTS AND METHODS We sequenced the coding sequence of S100A2 gene in normal oral keratinocytes (NOKs), dysplastic oral keratinocytes (DOKs), eight oral cancer lines, and 54 pairwise oral cancer specimens. We also compared the in vitro anti-tumor effect of wildtype (G allele) and variant (A allele) S100A2 expression using cell proliferation, migration, invasion, and colony formation assays. RESULTS With the exception of CAL27 and SCC-15 cancer lines being heterozygotes of A and G alleles, the remaining oral cells were homozygotic in G alleles. No alterations of anti-growth, anti-migration, anti-invasion, and anti-colony formation were observed between variant and wildtype cells. Moreover, no minor S100A2_185A allele was detected in 54-pairwise clinical specimens. CONCLUSION The coding sequence polymorphism S100A2_185G>A had no regulatory role in S100A2-mediated tumor suppression in oral cancer.

Utilizing glycine N-methyltransferasegene knockout mice as a model for identification of missing proteins in hepatocellular carcinoma

Glycine N-methyltransferase is a tumor suppressor gene for hepatocellular carcinoma, which can activate DNA methylation by inducing the S-adenosylmethionine to S-adenosylhomocystine. Previous studies have indicated that the expression of Glycine N-methyltransferase is inhibited in hepatocellular carcinoma. To confirm and identify missing proteins, the pathologic analysis of the tumor-bearing mice will provide critical histologic information. Such a mouse model is applied as a screening tool for hepatocellular carcinoma as well as a strategy for missing protein discovery. In this study we designed an analysis platform using the human proteome atlas to compare the possible missing proteins to human whole chromosomes. This will integrate the information from animal studies to establish an optimal technique in the missing protein biomarker discovery.

Preparation and Characterization of Hyaluronic Acid-Polycaprolactone Copolymer Micelles for the Drug Delivery of Radioactive Iodine-131 Labeled Lipiodol

Micelles, with the structure of amphiphilic molecules including a hydrophilic head and a hydrophobic tail, are recently developed as nanocarriers for the delivery of drugs with poor solubility. In addition, micelles have shown many advantages, such as enhanced permeation and retention (EPR) effects, prolonged circulation times, and increased endocytosis through surface modification. In this study, we measured the critical micelle concentrations, diameters, stability, and cytotoxicity and the cell uptake of micelles against hepatic cells with two kinds of hydrophilic materials: PEG-PCL and HA-g-PCL. We used 131I as a radioactive tracer to evaluate the stability, drug delivery, and cell uptake activity of the micelles. The results showed that HA-g-PCL micelles exhibited higher drug encapsulation efficiency and stability in aqueous solutions. In addition, the 131I-lipiodol loaded HA-g-PCL micelles had better affinity and higher cytotoxicity compared to HepG2 cells.