Biomedical subjects

A P W Yuen

Publications and source records attributed to A P W Yuen.

4 recordsLinked to original sources

PubMed2006

Molecular and cytogenetic changes involved in the immortalization of nasopharyngeal epithelial cells by telomerase.

Nasopharyngeal carcinoma (NPC) is a common disease in Hong Kong and southern provinces of China. EBV infection is believed to play a critical role in the development of NPC. Previous studies on the transformation mechanism of EBV genes were mostly performed in either NPC or nonnasopharyngeal epithelial cells which may not be representative of premalignant nasopharyngeal epithelial cells. Establishment of a representative cell system would greatly facilitate the elucidation of the role of EBV infection in the development of NPC. Using telomerase alone, we were able to establish an immortalized nasopharyngeal epithelial cell line from primary nonmalignant nasopharyngeal biopsies. The telomerase-immortalized nasopharyngeal epithelial cells are largely diploid in karyotype. Interestingly, this newly immortalized nasopharyngeal epithelial cell line, referred as NP460hTert, harbors genetic alterations previously identified in premalignant and malignant nasopharyngeal epithelial cells. These include inactivation of p16 by homozygous deletion of the p16(INK4A) locus and downregulation of RASSF1A expression. The deletion of the p16(INK4A) locus appears to be the most crucial event for the immortalization of nasopharyngeal epithelial cells by telomerase and precedes RASSF1A downregulation. In addition, detailed analysis of the cytogenetic changes by conventional cytogenetics, spectral karyotyping (SKY) and array-based CGH revealed a gain of a 17q21-q25 fragment on 11p15 chromosome in all NP460hTert cells which occurred before deletion of the p16(INK4A) locus. Gain of 17q has been previously reported in NPC. In addition, activation of NF-kappaB was observed in immortalized NP460hTert cells at the later population doublings, and may play a role in the survival of immortalized NP epithelial cells. Id1 which is commonly expressed in various human cancers, including NPC, was also upregulated in the immortalized NP460hTert cells. Thus, the establishment of an immortalized nasopharyngeal epithelial cell line harboring common genetic alterations present in premalignant and cancerous nasopharyngeal epithelial cells may provide a valuable cell system to examine for early events involved in NPC carcinogenesis, particularly in elucidating the role of EBV infection in NPC development.

Cell Proliferation↗

PubMed2004

Nonhematologic malignancies after allogeneic hematopoietic stem cell transplantation: incidence and molecular monitoring.

Survivors of allogeneic hematopoietic stem cell transplantation (HSCT) are at a life-long increased risk of secondary nonhematologic malignancies. In 615 adult Chinese allogeneic HSCT patients, nine developed nonhematologic malignancies. The 5-year cumulative incidence was 6.1%, 4.5 times the background cancer incidence. Early-onset (within first 6 months) and late-onset (>3 years) subtypes were observed. Secondary cancers included hepatocellular carcinoma, oral and esophageal squamous cell tumors and lung adenocarcinoma in a female nonsmoker. The spectrum reflected local cancer epidemiology, which was different from Western populations. The pathogenesis might be related to acceleration of pre-existing cancers (early-onset type), or prolonged immunosuppression (late-onset type). DNA chimerism studies showed that all tumors were recipient-derived. In the plasma, DNA in all cases was apparently donor-derived, although aberrantly methylated p15 was detectable in a patient with a p15-methylated secondary cancer, implying that minute quantities of tumor (and therefore recipient) derived DNA might be present.

Adult↗

PubMed2002

Clinicopathologic significance of bcl-2 expression in the surgical treatment of oral tongue carcinoma.

AIM: There is still controversy on the incidence of positive expression of bcl-2 and its prognostic significance for oral tongue carcinoma patients who are treated by surgery. The present study aims at resolving the controversy on the clinicopathologic significance of bcl-2 in a well selected group of patients who satisfy the recruitment criteria: (1) oral tongue carcinoma, (2) squamous cell carcinoma, (3) primary surgical treatment. METHOD: Bcl-2 expression was studied by immunohistochemistry on glossectomy specimens of 73 patients. The expression of bcl-2 was correlated with clinicopathologic data. RESULTS: Of the 73 tumours, 11% had positive expression of bcl-2. Bcl-2 expression was not significantly correlated with tumour grade, stage, nodal metastasis and survival. CONCLUSION: Bcl-2 expression played a minor role in oral tongue carcinoma. It had no significant correlation with tumour grade, stage and nodal metastasis. It also had no prognostic value on survival for patients who were treated by primary surgery.

Adolescent↗

PubMed2002

Endoscopic transnasal orbital decompression for thyrotoxic orbitopathy.

OBJECTIVE: To evaluate the efficacy of endoscopic transnasal orbital decompression alone for thyrotoxic orbitopathy. DESIGN: Retrospective review of consecutive procedures. SETTING: Tertiary referral otorhinolaryngology centre. PATIENTS: Twenty-three eyes of 14 patients. INTERVENTION: Endoscopic transnasal orbital decompression. MAIN OUTCOME MEASURES: Proptosis reduction, intra-ocular pressure reduction, exposure keratitis reduction, visual acuity improvement, and complication rate. RESULTS: There were no surgical complications for the 23 orbital decompressions. Proptosis reduction was achieved in 22 (96%) eyes. The mean proptosis reduction was 4.6 mm (median, 5.0 mm; range, 1.0-8.0 mm). The postoperative intra-ocular pressure decreased after surgical decompression in 20 (87%) eyes with a mean reduction of 11 mm Hg (median, 6 mm Hg; range, 1-35 mm Hg). Of the 15 eyes with incomplete closure of the eyelid before the operation, 11 (73%) had complete eyelid closure after surgical decompression. Of the other four eyes that had incomplete closure, the gaps were reduced. The visual acuity was improved for 16 (70%) eyes with a median improvement of 3 Snellen lines (range, 1-8 lines). CONCLUSION: Endoscopic transnasal medio-inferior orbital wall decompression is a safe and adequate treatment for thyrotoxic orbitopathy with proptosis, exposure keratitis, and visual loss.

Adult↗