Li-Ing Ho

Down regulation of bcl‐2 by p53 in nasopharyngeal carcinoma and lack of detection of its specific t(14;18) chromosomal translocation in fixed tissues

High levels of bcl‐2 protein have been found in a wide variety of human cancers. Since p53 gene inactivation occurs in over half of human cancers, it is possible that loss of p53‐mediated repression of bcl‐2 gene expression accounts, at least in part, for the frequent abnormalities in bcl‐2 protein production seen in tumours. By using immunohistochemical methods, we have analysed thirty‐three nasopharyngeal carcinomas for p53 and bcl‐2 expression. We found an inverse correlation between the expression of these two proteins (Pu2003<u20030.001). Moreover, we utilized universal oligonucelotide primers of a region 5′ to the bcl‐2 MBR and at the 3′ end of JH segments to initiate a DNA polymerase chain reaction that amplified these bcl‐2‐JH junctures. Of the twelve nasopharyngeal carcinomas expressing bcl‐2, none showed a t(14;18) chromosome translocation. These findings may indicate potential mechanisms by which bcl‐2 regulates apoptosis.

Differential expression of the human metastasis adhesion molecule CD44V in normal and carcinomatous stomach mucosa of chinese subjects

Background. CD44 is a cell surface adhesion molecule involved in cell‐cell and cell‐matrix interactions. Tumor cells transfected to overexpress the isoform CD44V readily gain access to lymph nodes and form distant metastases.

Apoptosis occurs more frequently in intraductal carcinoma than in infiltrating duct carcinoma of human breast cancer and correlates with altered p53 expression: Detected by terminal-deoxynucleotidyl-transferase- mediated dUTP-FITC nick end labelling (TUNEL)

We examined the relationship between apoptosis and three different major stages of human breast carcinoma: intraductal carcinoma (DCIS), infiltrating duct carcinoma (IDC) and metastatic carcinoma in lymph nodes. We also determined the correlation between apoptosis and oestrogen receptor (ER), progesterone receptor (PR) and p53.

Overexpression of the orphan receptor Nur77 and its translocation induced by PCH4 may inhibit malignant glioma cell growth and induce cell apoptosis.

In previous study, n‐butylidenephthalide (BP), a natural compound from Angelica sinensis, has anti‐glioblastoma multiform (GBM) cell effects. In this study, we modified BP structure to increase anti‐GBM cell effects. The anti‐GBM cell effects of one derivative of BP, (Z)‐N‐(2‐(dimethylamino)ethyl)‐2‐(3‐((3‐oxoisobenzofuran‐1(3H)‐ylidene)methyl)phenoxy)acetamide (PCH4) were tested in vitro and in vivo.

Apoptosis in nasopharyngeal carcinoma as related to histopathological characteristics and clinical stage

We investigated the significance of apoptosis, using the terminal deoxynucleotidyl transferase mediated dUTP‐digoxigenin nick end‐labelling method, in nasopharyngeal carcinoma biopsy samples.

Hyaluronate binding assay study of transfected CD44 V4–V7 isoforms into the human gastric carcinoma cell line SC-M1

The potential human metastasis molecule CD44 and its isoforms V5 and V6 are overexpressed in human gastric carcinoma. Among the numerous extracellular matrix components, hyaluronate, a CD44 ligand, is of increasing interest in relation to its role in cancer cell development and invasion. By using the dynabead separation method, the SC‐M1 cell line was separated into V5 and V6 isoform‐positive and ‐negative populations. The V5 and V6 isoform‐negative populations exhibited significantly higher hyaluronate binding activity than the corresponding positive cells. The hyaluronate binding activity of V5 and V6‐positive cells could be restored by pretreatment with anti‐CD44 V5 and V6 monoclonal antibodies (MAbs). In addition, transfection of an expression vector containing CD44 V5 and V6 into V5 and V6‐negative cells decreased their hyaluronate binding activity to the levels of CD44 V5 and V6‐positive cells. Cells transfected with V5 and V6 recovered their hyaluronate binding activity after pretreatment with MAbs against V5 and V6. These data suggest that cell adhesion involving hyaluronate can be regulated by multiple mechanisms, one of which involves alternative splicing of CD44 isoforms.

Non-Canonical Regulation of Type I Collagen through Promoter Binding of SOX2 and Its Contribution to Ameliorating Pulmonary Fibrosis by Butylidenephthalide

Pulmonary fibrosis is a fatal respiratory disease that gradually leads to dyspnea, mainly accompanied by excessive collagen production in the fibroblast and myofibroblast through mechanisms such as abnormal alveolar epithelial cells remodeling and stimulation of the extracellular matrix (ECM). Our results show that a small molecule, butylidenephthalide (BP), reduces type I collagen (COL1) expression in Transforming Growth Factor beta (TGF-β)-induced lung fibroblast without altering downstream pathways of TGF-β, such as Smad phosphorylation. Treatment of BP also reduces the expression of transcription factor Sex Determining Region Y-box 2 (SOX2), and the ectopic expression of SOX2 overcomes the inhibitory actions of BP on COL1 expression. We also found that serial deletion of the SOX2 binding site on 3′COL1 promoter results in a marked reduction in luciferase activity. Moreover, chromatin immunoprecipitation, which was found on the SOX2 binding site of the COL1 promoter, decreases in BP-treated cells. In an in vivo study using a bleomycin-induced pulmonary fibrosis C57BL/6 mice model, mice treated with BP displayed reduced lung fibrosis and collagen deposition, recovering in their pulmonary ventilation function. The reduction of SOX2 expression in BP-treated lung tissues is consistent with our findings in the fibroblast. This is the first report that reveals a non-canonical regulation of COL1 promoter via SOX2 binding, and contributes to the amelioration of pulmonary fibrosis by BP treatment.