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Hui-Ling Yen,
Heather Forrest,
Peter Cheung,
Diana Wong,
Olive Li,
Scott Krauss,
Angela Ferguson,
Jeri-Carol Crumpton,
Jeremy Jones,
Terry Choy,
Edward Ma,
Leo L M Poon,
Gavin J Smith, John Nicholls,
Yi Guan,
Robert G Webster,
Richard Webby,
Joseph Sriyal Malik Peiris
Influenza and Other Respiratory Viruses 05/2011; 5 Suppl 1:85-7. · 4.16 Impact Factor
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ABSTRACT: This single-center, phase II study assessed the safety/tolerability and initial efficacy of gefitinib in patients with nasopharyngeal carcinoma (NPC) pretreated with platinum-based chemotherapy.
Patients with recurrent and metastatic NPC who had treatment failure with at least 2 lines of chemotherapy including platinum were given gefitinib at a fixed dose of 250 mg daily. Treatment was continued until the patient experienced unacceptable side effects or disease progression.
Nineteen patients were enrolled, having had treatment failure with a median of 2 chemotherapy regimens. Treatment was well tolerated, and only grades 1 to 2 adverse events were observed. None of the patients achieved partial or complete response. Median time-to-progression was 4 months, and median overall survival was 16 months.
Gefitinib was well tolerated, but the response rate was poor in this heavily pretreated study population, and its use in NPC is not recommended outside the context of clinical trial.
Head & Neck 08/2008; 30(7):863-7. · 2.40 Impact Factor
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ABSTRACT: Highly pathogenic avian influenza (HPAI) H5N1 has spread globally in birds and infected over 270 humans with an apparently high mortality rate. Serologic studies to determine the extent of asymptomatic H5N1 infection in humans and other mammals and to investigate the immunogenicity of current H5N1 vaccine candidates have been hampered by the biosafety requirements needed for H5N1 micro-neutralization tests.
Development of a serodiagnostic tool for highly pathogenic influenza that reproduces H5N1 biology but can be used with less biohazard.
We have generated and evaluated H5 hemagglutinin pseudotyped lentiviral particles encoding the luciferase reporter (H5pp).
H5pp entry into target cells depends on alpha2-3 cell surface sialic acids and requires low pH for membrane fusion. H5pp infectivity is specifically neutralized by sera from patients and animals infected with H5N1 and correlates well with conventional microneutralization test.
H5pp reproduce H5N1 influenza virus entry into target cells and potentially provides a high-throughput and safe method for sero-epidemiology.
Journal of Clinical Virology 06/2007; 39(1):27-33. · 3.97 Impact Factor
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Nature Medicine 09/2005; 11(8):821-2. · 22.46 Impact Factor
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ABSTRACT: Epstein-Barr virus (EBV) is present within the tumor cells of most cases of nasopharyngeal carcinoma (NPC). Recent studies suggest that tumor burden is proportional to the level of EBV DNA in blood and that rapid blood testing can be used to guide therapeutic intervention. The relative utility of viral load vs. serology has been insufficiently studied. In our study, EBV viral load was measured by quantitative PCR using either real-time or end-point detection systems in serum samples from 124 NPC patients (93 pretreatment, 13 relapsed, 18 in remission) and 40 controls. Serologic titers against EBV early antigen were measured in the same serum samples. EBV DNA was detectable in 64 of 93 untreated NPC patients (69%; mean viral load 11,211 copies/ml), 11 of 13 relapsed NPC patients (85%; mean 53,039 copies/ml) and 0 of 18 remission patients. EBV DNA was detectable in only 1 of 40 non-NPC controls (3%). In 34 instances where paired plasma and serum samples were available for testing, both were effective sample types, and there was no significant difference between end-point and real-time methods for measuring viral load. Early antigen (EA) IgA and IgG titers were elevated in most NPC patients regardless of whether their disease was active or in remission. EBV viral load was more informative than was EA serology for distinguishing remission from relapsed disease. EBV DNA measurement appears to be a noninvasive way to monitor tumor burden after therapy.
International Journal of Cancer 01/2005; 112(6):1036-41. · 5.44 Impact Factor
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ABSTRACT: The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is one of two postulated viral oncogenic proteins. Sequence variations, and in particular a 30 base pair deletion variant called CAO, may define different disease populations. We developed a panel of rat monoclonal antibodies (MAb) specific for the non-wild type LMP1 and compared the presence of the antibody staining with LMP1 DNA sequence analysis on clinical samples of nasopharyngeal carcinoma, peripheral T-cell lymphoma (PTCL), Hodgkin's disease, lymphoblastoid cell lines (LCL) from normal volunteers, and patients with nasopharyngeal carcinoma. The results demonstrate specificity of the monoclonal cocktail for detecting the non-wild type LMP1 and the ability to sub-differentiate between the mediterranean type of LMP1 and the CAO-LMP1. Double immunofluorescence on paraffin material using the traditional CS1-4 monoclonal antibodies and the CAO-cocktail revealed no dual population of cells in the biopsy material from the Asian region.
Journal of Virological Methods 04/2004; 116(1):79-88. · 2.01 Impact Factor
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ABSTRACT: Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus, called the SARS coronavirus (SARS-CoV). Over 95% of well characterized cohorts of SARS have evidence of recent SARS-CoV infection. The genome of SARS-CoV has been sequenced and it is not related to any of the previously known human or animal coronaviruses. It is probable that SARS-CoV was an animal virus that adapted to human-human transmission in the recent past. The virus can be found in nasopharyngeal aspirate, urine and stools of SARS patients. Second generation reverse transcriptase polymerase chain reaction assays are able to detect SARS-CoV in nasopharyngeal aspirates of approximately 80% of patients with SARS within the first 3 days of illness. Seroconversion for SARS-CoV using immunofluorescence on infected cells is an excellent method of confirming the diagnosis, but antibody responses only appear around day 10 of the illness. Within the first 10 days the histological picture is that of acute phase diffuse alveolar damage (DAD) with a mixture of inflammatory infiltrate, oedema and hyaline membrane formation. Desquamation of pneumocytes is prominent and consistent. After 10 days of illness the picture changes to one of organizing DAD with increased fibrosis, squamous metaplasia and multinucleated giant cells. The role of cytokines in the pathogenesis of SARS is still unclear.
Respirology 12/2003; 8 Suppl:S6-8. · 2.42 Impact Factor
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John Nicholls,
Elisabeth Kremmer,
Clement A. Meseda,
Mike Mackett,
Peter Hahn,
Margaret L. Gulley,
Antoinette Brink,
Lode J. Swinnen,
John Greenspan,
Yvonne De Souza,
Friedrich Grässer,
Jonathan Sham,
Mun-Hon Ng,
John R. Arrand
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ABSTRACT: Epstein-Barr virus (EBV) has been identified in a wide range of neoplastic and non-neoplastic disorders. The EBV open reading frame BHRF1 encodes a protein with partial sequence and functional homology to the anti-apoptotic onco-protein Bcl-2 and may therefore have a role in the proliferation of EBV positive cells. We have developed a rat monoclonal antibody against pBHRF1, which can detect BHRF1 in paraffin sections. While a number of mutant versions of BHRF1 were recognised, the monoclonal did not detect the BHRF1 homologue encoded by Herpesvirus papio or two mutants with deletions in the BH2 region. This novel rat monoclonal antibody (6A9) was used to examine tissue sections from 39 cases of non-keratinising undifferentiated nasopharyngeal carcinoma (NPC), 6 cases of metastatic NPC, 7 cases of EBV-positive NPC with squamous differentiation from Chinese patients, 15 cases of EBV-positive post-transplant lymphoproliferative disorder (PTLD), 6 EBV-containing lymphoblastoid cell lines, and 2 cases of oral hairy leukoplakia (OHL). In 11 cases of undifferentiated NPC, RT-PCR data were available for comparison with the immunohistochemistry. Both cases of OHL and two cases of LCL were positive for BHRF1 but none of the PTLD showed positive staining. All cases of undifferentiated NPC were positive for Bcl-2 but only one BHRF1 positive cell was identified in 1 of 39 cases of primary undifferentiated NPC. The 6A9 antibody produced less background staining and no nuclear positivity compared with the commercially available mouse monoclonal 5B11. It is concluded that BHRF1 can not be detected by immunohistochemistry in NPC and therefore it appears not to play a significant anti-apoptotic role in the progression of this EBV-associated tumour. The 6A9 monoclonal appears to be superior to 5B11 for the detection of pBHRF1 in tissue sections. J. Med. Virol. 65:105–113, 2001. © 2001 Wiley-Liss, Inc.
Journal of Medical Virology 07/2001; 65(1):105 - 113. · 2.82 Impact Factor
