51 research outputs found
Epstein-Barr virus latent membrane protein-1 (LMP-1) 30-bp deletion and Xho I-loss is associated with type III nasopharyngeal carcinoma in Malaysia
Background: Nasopharyngeal carcinoma (NPC) is a human epithelial tumour with high prevalence amongst Chinese in
Southern China and South East Asia and is associated with the Epstein-Barr virus (EBV). The viral genome harbours an
oncogene, namely, the latent membrane protein 1 (LMP1) gene and known variants such as the 30-bp deletion and loss
of XhoI restriction site have been found. Less is known about the relationship between these variants and the population
characteristics and histological type.
Methods: In this study, the EBV LMP1 gene variants from 42 NPC and 10 non-malignant archived formalin fixed, paraffinembedded
tissues, as well as plasma from another 35 patients with nasopharyngeal carcinoma were determined by using
Polymerase Chain Reaction (PCR). Statistical analysis was performed by using SPSS programme.
Results: LMP1 30-bp deletion was detected in 19/34 (55.9%) of NPC tissues, 7/29 (24.1%) of plasma but absent in nonmalignant
tissues (8/8). Coexistence of variants with and without 30bp deletion was found only in 5/29 (17.2%) plasma
samples but not in NPC tissues. The loss of XhoI restriction site in LMP1 gene was found in 34/39 (87.2%) of the NPC
tissues and 11/30 (36.7%) of plasma samples. None of the non-malignant nasopharyngeal tissues (8/8) harbour XhoI-loss
variants. LMP1 30-bp deletion was detected in 16/18 Chinese versus 3/15 Malays and 13/16 type III (undifferentiated
carcinoma) versus 1/6 type I (keratinizing squamous cell carcinoma). XhoI-loss was found in 19/19 Chinese versus 14/19
Malays and 18/18 type III (undifferentiated) versus 2/5 type I (keratinizing squamous cell carcinoma). Statistical analysis
showed that these variants were associated with ethnic race (30-bp deletion, p < 0.05; XhoI-loss, p = 0.046) and
histological type of NPC (30-bp deletion, p = 0.011; XhoI-loss, p = 0.006). Nineteen out of 32 NPC tissues (19/32; 59.4%)
and 6/24 (25%) of plasma samples showed the coexistence of both the 30-bp deletion and the loss of XhoI restriction
site. A significant relationship was found with the Chinese race but not histological type.
Conclusion: The incidence rate of 56% for LMP1 30-bp deletion was lower compared to previously reported rates of
75–100% in NPC tissues. Coexistence of variants with and without 30-bp deletion was found only in 5/29 plasma samples.
The incidence rate of XhoI restriction site loss in NPC was comparable to other studies from endemic regions such as
Southern China. For the first time, the presence of LMP1 30-bp deletion or XhoI-loss was associated with the Chinese
race and type III NPC. Both these variants were not found in non-malignant tissues. The influence of these variants on
disease progression and outcome in Chinese and type III NPC requires further investigation
Anxiety and depressive symptoms and coping strategies in Nasopharyngeal carcinoma patients in Hospital Kuala Lumpur
Introduction: Nasopharyngeal Carcinoma (NPC) is the second most common cancer
among men in Malaysia. Establishing local data will help to improve the treatment strategies
and lower the anxiety and depression level among NPC patients. Our aim was to compare
the level of symptoms of anxiety and depression and the coping strategies employed
between NPC and cancer-free patients. Methods: A comparative cross-sectional study
with universal sampling was conducted on 22 NPC patients and 30 cancer-free patients
from the Oncology and Radiotherapy Department and Ear, Nose and Throat clinic of
Hospital Kuala Lumpur (HKL) between 12 to 29 May 2008. In this study, the symptoms
of depression and anxiety were obtained by using the Hospital Anxiety and Depression
Scale (HADS) while Brief COPE questionnaire was used to understand patients’ coping
strategies. Results: The prevalence of NPC was higher in the Chinese, men, aged between
40 and 59 years, and those from the lower income group. The levels of anxiety and
depression symptoms were found to be higher in the NPC group as compared to the
cancer-free group. However, only the level of depression was found significantly related to
the NPC group (p=0.002). This study also found that the two comparison groups were
using different types of coping strategies. The NPC patients mainly used ‘acceptance’ as
their coping strategy while the comparative group most often used ‘religion’. Among the
types of coping strategies reported by the patients, ‘use of instrumental support’ type
was found to be associated with a lower level of anxiety (p = 0.035) and ‘humour’ type
was associated with lower depressive symptoms (p = 0.269). On the contrary, ‘selfblame’
type was associated with both anxiety (p =0.0001) and depression (p = 0.001)
symptoms. In addition, patients with different gender, ethnicity, educational levels, and
monthly income were also found to have significant differences in their levels of anxiety
and depression as well as type of coping strategies. Conclusions: NPC patients had
higher anxiety and depression levels as compared to the comparative group. Different
socio-demographic backgrounds and different types of coping strategies had an influence
on patients resulting in different levels of anxiety and depression
Proef met in de kas gekweekte Ixia- en gladiolenknollen, 1948-1949
NPC plasma that display 30-bp deletion (product size = 156-bp), 2–4-NPC plasma without the 30-bp deletion (product size = 186-bp).<p><b>Copyright information:</b></p><p>Taken from "Epstein-Barr virus latent membrane protein-1 (LMP-1) 30-bp deletion and I-loss is associated with type III nasopharyngeal carcinoma in Malaysia"</p><p>http://www.wjso.com/content/6/1/18</p><p>World Journal of Surgical Oncology 2008;6():18-18.</p><p>Published online 15 Feb 2008</p><p>PMCID:PMC2265716.</p><p></p
Ethnicity influences disease characteristics and symptom severity in allergic rhinitis patients in Malaysia
Background: The number of available reports regarding the influence of ethnicity on clinical features of allergic rhinitis (AR), especially disease severity in tropical climates, is limited. We aimed to compare clinical parameters and disease severity in AR patients of different ethnicities.
Methods: Malay, Chinese, and Indian AR patients (n = 138) with confirmed sensitivity to Dermatophagoides pteronyssinus, Dematophagoides farinae, and Blomia tropicalis were tested for mite-specific immunoglobulin E (sIgE) levels. A detailed questionnaire was used to collect data on nasal symptom score (NSS), ocular symptom score (OSS), sum of symptoms score (SSS), quality of life score (QLS), symptomatic control score (SCS), and total sum of scores (TSS) and correlate the derived data with patients' demography, mite-polysensitivity, and sIgE levels.
Results: AR-related symptoms were most severe in Malays and least in Chinese (p < 0.01). Age (r = 0.516 to 0.673, p < 0.05) and duration of AR (r = 0.635 to 0.726, p < 0.01) correlated positively with severity domains (NSS, SSS, QLS, and TSS) in Chinese. Duration of concurrent allergies was highest in Malays (p < 0.05). Polysensitivity predicted increased sIgE levels in Malays (r = 0.464 to 0.551, p < 0.01) and Indians (r = 0.541 to 0.645, p < 0.05) but affected NSS, SSS, and TSS only in Indians (r = 0.216 to 0.376, p < 0.05). sIgE levels were lowest among Chinese but correlated strongly with NSS, OSS, SSS, and TSS (r = 0408 to 0.898, p < 0.05).
Conclusion: Clinical parameters in AR may be influenced by race. Symptoms were most severe among Malays but did not correlate with other variables examined. Although Indian ethnicity did not impact disease severity, duration of concurrent allergies and mite-polysensitivity was associated with more severe disease. Age, duration of disease, and sIgE levels may be useful indicators of disease severity in Chinese
HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese
Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1) infection. We carried out a genome-wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA-A to NPC with the strongest signal detected in rs3869062 (p=1.73 3 10-9). HLA-A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (pHLA-A-aa-site-99=3.79 × 10-8, prs1136697=3.79 × 10-8) and T-cell receptor binding site (pHLA-A-aa-site-145=1.41 × 1024, prs1059520=1.41 × 10-4) of the HLA-A. We also detected strong association signals in the 50-UTR region with predicted active promoter states (prs41545520=7.91 × 10-8). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520-G correlated with reduced HLA-A expression. Multivariate logistic regression diminished the effects of HLA-A amino acid variants and SNPs, indicating a correlation with the effects of HLA-A∗11:01, and to a lesser extent HLA-A∗02:07. We report the strong genetic influence of HLA-A on NPC susceptibility in the Malaysian Chinese. © 2014 UICC
Systematic comparison of plasma EBV DNA, anti-EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma
Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein-Barr virus (EBV)-associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost-effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI-W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI-W 121 bp and ebv-miR-BART7-3p were validated. Hsa-miR-29a-3p and hsa-miR-103a-3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI-W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling
Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19
Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe
Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies
There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity
Epstein-barr virus specific immunogen
The present invention relates to an Epstein-Barr virus specific immunogen based on the LMP2 (latent membrane protein 2) gene. Furthermore, the present invention describes variants of the immunogen as well as polynucleotides coding for the peptide-immunogen and host cells transfected with the polynucleotides. The immunogens of the present invention are specifically useful to induce an CTL immune response in patient suffering from nsaopharyngeal carcinoma. Also embodied are novel methods for the in-vitro activation of CTLs using the aforementioned immunogens
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