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2.  Genomic Diversity of Epstein-Barr Virus Genomes Isolated from Primary Nasopharyngeal Carcinoma Biopsy Samples 
Journal of Virology  2014;88(18):10662-10672.
ABSTRACT
Undifferentiated nasopharyngeal carcinoma (NPC) has a 100% association with Epstein-Barr virus (EBV). However, only three EBV genomes isolated from NPC patients have been sequenced to date, and the role of EBV genomic variations in the pathogenesis of NPC is unclear. We sought to obtain the sequences of EBV genomes in multiple NPC biopsy specimens in the same geographic location in order to reveal their sequence diversity. Three published EBV (B95-8, C666-1, and HKNPC1) genomes were first resequenced using the sequencing workflow of target enrichment of EBV DNA by hybridization, followed by next-generation sequencing, de novo assembly, and joining of contigs by Sanger sequencing. The sequences of eight NPC biopsy specimen-derived EBV (NPC-EBV) genomes, designated HKNPC2 to HKNPC9, were then determined. They harbored 1,736 variations in total, including 1,601 substitutions, 64 insertions, and 71 deletions, compared to the reference EBV. Furthermore, genes encoding latent, early lytic, and tegument proteins and glycoproteins were found to contain nonsynonymous mutations of potential biological significance. Phylogenetic analysis showed that the HKNPC6 and -7 genomes, which were isolated from tumor biopsy specimens of advanced metastatic NPC cases, were distinct from the other six NPC-EBV genomes, suggesting the presence of at least two parental lineages of EBV among the NPC-EBV genomes. In conclusion, much greater sequence diversity among EBV isolates derived from NPC biopsy specimens is demonstrated on a whole-genome level through a complete sequencing workflow. Large-scale sequencing and comparison of EBV genomes isolated from NPC and normal subjects should be performed to assess whether EBV genomic variations contribute to NPC pathogenesis.
IMPORTANCE This study established a sequencing workflow from EBV DNA capture and sequencing to de novo assembly and contig joining. We reported eight newly sequenced EBV genomes isolated from primary NPC biopsy specimens and revealed the sequence diversity on a whole-genome level among these EBV isolates. At least two lineages of EBV strains are observed, and recombination among these lineages is inferred. Our study has demonstrated the value of, and provided a platform for, genome sequencing of EBV.
doi:10.1128/JVI.01665-14
PMCID: PMC4178900  PMID: 24991008
4.  Evaluation of radiation-induced changes to parotid glands following conventional radiotherapy in patients with nasopharygneal carcinoma 
The British Journal of Radiology  2011;84(1005):843-849.
Objectives
Xerostomia is a common post-radiotherapy (post-RT) complication in nasopharyngeal carcinoma (NPC) patients. This study evaluated the relation of post-RT parotid gland changes with the dose received.
Methods
Data from 18 NPC patients treated by radiotherapy between 1997 and 2001 were collected. Parotid gland volumes were measured and compared between their pre-RT and post-RT CT images; both sets of CT were conducted with the same scanning protocol. Doppler ultrasound was used to assess the haemodynamic condition of the glands after radiotherapy. Doppler ultrasound results were compared against 18 age-matched normal participants. A questionnaire was used to evaluate the patients' comments of xerostomia condition. Radiotherapy treatment plans of the participants were retrieved from the Eclipse treatment planning system from which the radiation doses delivered to the parotid glands were estimated. The correlations of parotid gland doses and the post-RT changes were evaluated.
Results
The post-RT parotid glands were significantly smaller (p<0.001) than the pre-RT ones. They also demonstrated lower vascular velocity, resistive and pulsatility indices (p<0.05) than normal participants. The degree of volume shrinkage and subjective severity of xerostomia demonstrated dose dependence, but such dependence was not definite in the haemodynamic changes.
Conclusion
It was possible to predict the gland volume change and subjective severity of xerostomia based on the dose to the parotid glands for NPC patients. However, such prediction was not effective for the vascular changes. The damage to the gland was long lasting and had significant effects on the patients' quality of life.
doi:10.1259/bjr/55873561
PMCID: PMC3473791  PMID: 21224300
5.  Assessment of post-radiotherapy salivary glands 
The British Journal of Radiology  2011;84(1001):393-402.
Salivary glands are usually irradiated during radiotherapy for head and neck cancers, which can lead to radiation-induced damage. Radiation-induced xerostomia (oral dryness) is the most common post-radiotherapy complication for head and neck cancer patients and can reduce the patient’s quality of life. Accurate and efficient salivary gland assessment methods provide a better understanding of the cause and degree of xerostomia, and may help in patient management. At present, there are different methods for the assessment of salivary gland hypofunction; however, none of them are considered to be standard procedure. This article reviews the value of common methods in the assessment of post-radiotherapy salivary glands.
doi:10.1259/bjr/66754762
PMCID: PMC3473647  PMID: 21511748
6.  The antiemetic efficacy of tropisetron plus dexamethasone as compared with conventional metoclopramide-dexamethasone combination in Orientals receiving cisplatin chemotherapy: a randomized crossover trial  
1We report a single-blind randomized crossover trial comparing the efficacy of tropisetron plus dexamethasone (TROPDEX) vs conventional combination of metoclopramide, dexamethasone and diphenhydramine (METDEX) in prevention of acute and delayed vomiting in Chinese patients receiving high dose cisplatin.
2Thirty-six consecutive patients with nasopharyngeal carcinoma were entered into the study, all received cisplatin at a dose range of 60–100 mg/m2. Patients were randomized in the sequence of antiemetic regimens used in two consecutive cycles.
3The TROPDEX regimen consisting of tropisetron 5 mg i.v. and dexamethasone 20 mg i.v. given on day 1 of chemotherapy, followed by oral maintenance with tropisetron 5 mg daily and dexamethasone 4 mg twice daily from day 2 to 6. The METDEX regimen consisting of metoclopramide 1 mg kg−1 i.v., dexamethasone 20 mg i.v. and diphenhydramine 25 mg i.v. given before chemotherapy and then 2 hourly for two more doses on day 1, followed by oral metoclopramide 20 mg 6 hourly from day 2 to 6.
4Complete control of acute vomiting was observed in 64% of patients with TROPDEX as compared with 14% with METDEX (P<0.01). While complete plus major control of acute vomiting was observed in 84% with TROPDEX as compared with 58% with METDEX. The mean vomiting episodes on day 1 were 1.4 with TROPDEX as compared with 3.5 with METDEX (P<0.01). There was, however, no significant difference between the two regimens in the control of delayed vomiting.
5When patients randomized to TROPDEX in the second cycle were compared with those with TROPDEX in the first cycle, the antiemetic efficacy was reduced, with mean acute vomiting episodes of 2 in the former compared with 0.8 in the latter (P<0.01).
6The most common adverse effect observed was headache in TROPDEX (27%) and dizziness in METDEX (40%).
7In conclusion, the antiemetic regimen TROPDEX is effective in Chinese patients receiving high dose cisplatin chemotherapy and is well tolerated. It is better than conventional METDEX regimen in the control of acute vomiting, but not in the control of delayed vomiting.
doi:10.1046/j.1365-2125.1996.03268.x
PMCID: PMC2042600  PMID: 8735681
antiemesis; cisplatin; tropisetron; dexamethasone; metoclopramide; Chinese

Results 1-6 (6)