Sir Pao Center for Cancer
Sir Pao Center for Cancer
Loong H.H.,Prince of Wales Hospital |
Ma B.B.Y.,Sir Pao Center for Cancer |
Ma B.B.Y.,Chinese University of Hong Kong
Hong Kong Journal of Radiology | Year: 2012
Mortality from metastatic colorectal cancer has declined over the past decade, partly due to improvement in survival secondary to incorporation of targeted biologics in the treatment paradigm. We are now witnessing a new wave of new therapeutic options that may further improve survival outcomes for patients with metastatic colorectal cancer. This review will discuss recently matured data on the treatment outcomes of new anti-angiogenic targeted therapies in metastatic colorectal cancer and how they may affect the practice of oncology. © 2012 Hong Kong College of Radiologists.
Wong J.H.T.,Sir Pao Center for Cancer |
Lui V.W.Y.,Sir Pao Center for Cancer |
Umezawa K.,Keio University |
Ho Y.,Sir Pao Center for Cancer |
And 6 more authors.
Cancer Letters | Year: 2010
Despite the demonstrated constitutive activation of NF-κB in nasopharyngeal carcinoma (NPC), the therapeutic potential of targeting this pathway has not been investigated. Here, we employed a small molecule inhibitor of NF-κB, DHMEQ (which mainly blocks nuclear translocation of activated NF-κB) and demonstrated significant inhibition of NPC cell proliferation, migration, invasion, as well as anchorage-independent growth. These antitumor effects were associated with induction of G2/M cell cycle arrest and apoptosis, and downregulation of NF-κB target genes (EGFR, cyclin D1 and survivin). This first demonstration of therapeutic benefits of NF-κB targeting in NPC implicates the importance of targeting this pathway in NPC. © 2009 Elsevier Ireland Ltd. All rights reserved.
Hu X.,Zhejiang University |
Sui X.,Zhejiang University |
Li L.,Sir Pao Center for Cancer |
Li L.,Chinese University of Hong Kong |
And 13 more authors.
Journal of Pathology | Year: 2013
Gastric and colorectal cancers are among the most common cancers worldwide and cause serious cancer mortality. Both epigenetic and genetic disruptions of tumour suppressor genes (TSGs) are frequently involved in their pathogenesis. Here, we studied the epigenetic and genetic alterations of a novel TSG-PCDH17 and its functions in the pathogenesis of these tumours. We found that PCDH17 was frequently silenced and methylated in almost all gastric and colorectal tumour cell lines as well as in ∼95% of primary tumours, but not in normal gastric and colonic mucosa. Moreover, its deletion was detected in only 18% of gastric and 12% of colorectal cancer tissues, suggesting that epigenetic and genetic inactivation of PCDH17 are both involved in gastric and colorectal tumourigenesis. PCDH17 protein expression was significantly correlated with low tumour stage and less lymph node metastasis of gastric and colorectal cancer patients, indicating its potential as a tumour marker. Restoring PCDH17 expression inhibited tumour cell growth in vitro and in vivo through promoting apoptosis, as evidenced by increased TUNEL staining and caspase-3 activation. Furthermore, PCDH17-induced autophagy, along with increased numbers of autophagic vacuoles and up-regulated autophagic proteins Atg-5, Atg-12 and LC3B II. Thus, PCDH17 acts as a tumour suppressor, exerting its anti-proliferative activity through inducing apoptosis and autophagy, and is frequently silenced in gastric and colorectal cancers. PCDH17 methylation is a tumour-specific event that could serve as an epigenetic biomarker for these tumours. Copyright © 2012 Pathological Society of Great Britain and Ireland.
PubMed | Sir Pao Center for Cancer
Type: | Journal: BMC cancer | Year: 2012
Epstein-Barr virus (EBV) establishes its latency in EBV-associated malignancies, accompanied by occasionally reactivated lytic cycle. Promoter CpG methylation of EBV genome plays an essential role in maintaining viral latency. Two immediate-early (IE) genes, BZLF1 and BRLF1, induce the switch from latent to lytic infection. Studies of methylation-dependent binding of BZLF1 and BRLF1 to EBV promoters have been well reported, but little is known about the methylation status of BZLF1 and BRLF1 promoters (Zp and Rp) in tumor samples.We evaluated the methylation profiles of Zp and Rp by methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS), as well as BZLF1 and BRLF1 expression by semiquantitative reverse transcription (RT)-PCR in tumors of epithelial, NK- and B-cell origins.We found that both Zp and Rp were hypermethylated in all studied EBV-positive cell lines and tumors of lymphoid (B- or NK cell) or epithelial origin, while unmethylated Zp and Rp alleles were detected in cell lines expressing BZLF1 and BRLF1. Following azacytidine treatment or combined with trichostatin A (TSA), the expression of BZLF1 and BRLF1 was restored along with concomitant promoter demethylation, which subsequently induced the reactivation of early lytic gene BHRF1 and late lytic gene BLLF1.Hypermethylation of Zp and Rp mediates the frequent silencing of BZLF1 and BRLF1 in EBV-associated tumors, which could be reactivated by demethylation agent and ultimately initiated the EBV lytic cascade.