Displaying publications 41 - 60 of 260 in total

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  1. Malignant tumours in Malaya
    Ahluwalia HS, Duguid JB
    Br. J. Cancer, 1966 Mar;20(1):12-5.
    PMID: 5949191
    Matched MeSH terms: Nasopharyngeal Neoplasms/epidemiology*
  2. Fulltext Incidence of nasopharyngeal carcinoma in Malaysia, with special reference to the state of Selangor
    Armstrong RW, Kutty MK, Dharmalingam SK
    Br. J. Cancer, 1974 Jul;30(1):86-94.
    PMID: 4413823
    A "registry" of all known cases of nasopharyngeal carcinoma in Malaysia, 1968-72, was established. Attention was focused on the State of Selangor where conditions are best for case finding. Age-adjusted incidence rates among Chinese males and females were 17·3 and 7·3 per 100,000; among Malay males and females, the rates were 2·5 and 0·3 and among Indian males, 1·1. The detailed ethnicity of 192 cases in Selangor was established. Estimated incidence rates for the Chinese sub-groups agreed with the pattern observed elsewhere: highest among the Cantonese, lowest among the Hokkien/Teochiu, with the Khek in between. There was no correlation between histological type and sub-ethnic group among the Chinese cases.
    Matched MeSH terms: Nasopharyngeal Neoplasms/epidemiology*; Nasopharyngeal Neoplasms/pathology
  3. Fulltext Lymphoepitheliomas of the cervical lymph nodes
    Loke YW
    Br. J. Cancer, 1965 Sep;19(3):482-5.
    PMID: 5833066 DOI: 10.1038/bjc.1965.56
    Matched MeSH terms: Nasopharyngeal Neoplasms/epidemiology; Nasopharyngeal Neoplasms/pathology*
  4. Descriptive epidemiology of nasopharyngeal carcinoma in Peninsular Malaysia
    Prasad U, Rampal L
    Cancer Causes Control, 1992 Mar;3(2):179-82.
    PMID: 1562708 DOI: 10.1007/BF00051659
    Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Malaysia, a country in Southeast Asia with a multiracial population. While hospital-based data on NPC and data from a few states have been reported, a comprehensive study involving every known NPC patient in the whole of Peninsular Malaysia in one particular year had never been done. In the present study, the computed incidence rate was not only adjusted for age, sex, ethnicity, and place of residence, but also direct standardization methods of Rothman and Dever were used to reduce any distortion. The mean age of the 365 new cases of NPC registered in 1988 was 46.8 years (SD +/- 12.2 years). The ages of patients ranged from 10 to 80 years. The incidence in both sexes rose after the age of 20-29 years and reached a plateau between 40 and 49 years. No further rise was exhibited after age 60 years. The Chinese had the highest age-adjusted incidence rates, particularly for the age group 40-49 years, where the incidence rate was 40.1 per 100,000 for males and 14.9 for females. The average age-adjusted male/female ratio was 2.8:1. Age-adjusted incidence varied by place of residence. The pattern that emerged from the data indicated the possibility of interaction between genetic susceptibility and environmental cofactors in the etiology of NPC.
    Matched MeSH terms: Nasopharyngeal Neoplasms/ethnology; Nasopharyngeal Neoplasms/epidemiology*
  5. High incidence of nasopharyngeal carcinoma in native people of Sarawak, Borneo Island
    Devi BC, Pisani P, Tang TS, Parkin DM
    Cancer Epidemiol Biomarkers Prev, 2004 Mar;13(3):482-6.
    PMID: 15006927
    Nasopharyngeal cancer (NPC) is generally a rare malignancy with a few well-known exceptions, notably South-East China. In this article, we describe evidence of a high risk of NPC in the population of Sarawak State, Malaysia, and particularly in one native ethnic group. Sarawak State is one of the two provinces of Malaysia located on the island of Borneo. The native population (71.6%) includes the Iban, Malay, Bidayuh, Melanau, and diverse smaller ethnic groups. The Chinese are the largest nonindigenous group (27.5%). We identified 392 newly diagnosed cases (292 males and 100 females) of NPC in 1996-1998 in Malaysian citizens, permanent residents of Sarawak. Age-standardized rates by sex and ethnic group were compared with the highest rates in the world. The age-adjusted rate (ASR) in Sarawak residents was 13.5/100,000 [95% confidence interval (CI) 12.2-15.0] and 6.2/100,000 (95% CI 5.7-6.7) in males and females, respectively. The risk in the Bidayuh people was 2.3-fold (M) and 1.9-fold (F) higher than the Sarawak average, and about 50% higher than that in Hong Kong-the highest recorded by any population-based registry for the same period. Local dietary habits, environmental exposures, and genetic susceptibility deserve investigation in this population.
    Matched MeSH terms: Nasopharyngeal Neoplasms/ethnology*; Nasopharyngeal Neoplasms/epidemiology*
  6. Fulltext A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry
    Bei JX, Su WH, Ng CC, Yu K, Chin YM, Lou PJ, et al.
    Cancer Epidemiol Biomarkers Prev, 2016 Jan;25(1):188-192.
    PMID: 26545403 DOI: 10.1158/1055-9965.EPI-15-0144
    BACKGROUND: Genetic loci within the major histocompatibility complex (MHC) have been associated with nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer, in several GWAS. Results outside this region have varied.

    METHODS: We conducted a meta-analysis of four NPC GWAS among Chinese individuals (2,152 cases; 3,740 controls). Forty-three noteworthy findings outside the MHC region were identified and targeted for replication in a pooled analysis of four independent case-control studies across three regions in Asia (4,716 cases; 5,379 controls). A meta-analysis that combined results from the initial GWA and replication studies was performed.

    RESULTS: In the combined meta-analysis, rs31489, located within the CLPTM1L/TERT region on chromosome 5p15.33, was strongly associated with NPC (OR = 0.81; P value 6.3 × 10(-13)). Our results also provide support for associations reported from published NPC GWAS-rs6774494 (P = 1.5 × 10(-12); located in the MECOM gene region), rs9510787 (P = 5.0 × 10(-10); located in the TNFRSF19 gene region), and rs1412829/rs4977756/rs1063192 (P = 2.8 × 10(-8), P = 7.0 × 10(-7), and P = 8.4 × 10(-7), respectively; located in the CDKN2A/B gene region).

    CONCLUSIONS: We have identified a novel association between genetic variation in the CLPTM1L/TERT region and NPC. Supporting our finding, rs31489 and other SNPs in this region have been reported to be associated with multiple cancer sites, candidate-based studies have reported associations between polymorphisms in this region and NPC, the TERT gene has been shown to be important for telomere maintenance and has been reported to be overexpressed in NPC, and an EBV protein expressed in NPC (LMP1) has been reported to modulate TERT expression/telomerase activity.

    IMPACT: Our finding suggests that factors involved in telomere length maintenance are involved in NPC pathogenesis.

    Matched MeSH terms: Nasopharyngeal Neoplasms/genetics*; Nasopharyngeal Neoplasms/pathology
  7. Chromosomal alterations in Malaysian patients with nasopharyngeal carcinoma analyzed by comparative genomic hybridization
    Natasya Naili MN, Hasnita CH, Shamim AK, Hasnan J, Fauziah MI, Narazah MY, et al.
    Cancer Genet. Cytogenet., 2010 Dec;203(2):309-12.
    PMID: 21156250 DOI: 10.1016/j.cancergencyto.2010.07.136
    Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Malaysia, mainly occurring among the Chinese population. To detect common genetic alterations in NPC, we screened seven cases of NPC using the comparative genomic hybridization (CGH) technique. Before proceeding to the CGH technique, the tumors were first confirmed to consist of 75% tumor cells or more. In brief, the technique consists of binding tumor DNA with normal DNA and human Cot-1 DNA, which is then hybridized to normal metaphase spreads. The slides were then counterstained with 4,6 diamino-2-phenylindole (DAPI II) for detection. Analyses were performed using CGH software (Cytovision). We found genetic alterations in all seven NPC samples. The common chromosomal gains (57%, four cases) were found on chromosome arms 1q, 4p, 5, 7q, 11, 14p, 15q, 18p, and 21p, and common chromosomal losses (43%, three cases) were found on chromosome arm 16p. Our results showed chromosomal alterations in all seven NPC cases in the Malaysian population. This result provides the platform for further investigations to locate tumor suppressor genes and oncogenes at specific chromosomal regions in Malaysian NPC patients.
    Matched MeSH terms: Nasopharyngeal Neoplasms/genetics; Nasopharyngeal Neoplasms/metabolism
  8. PIK3CA gene mutations in breast carcinoma in Malaysian patients
    Ching-Shian Leong V, Jabal MF, Leong PP, Abdullah MA, Gul YA, Seow HF
    Cancer Genet. Cytogenet., 2008 Dec;187(2):74-9.
    PMID: 19027487 DOI: 10.1016/j.cancergencyto.2008.07.005
    Somatic mutations of phosphoinositide-3-kinase, catalytic, alpha; PIK3CA gene have been reported in several types of human cancers. The majority of the PIK3CA mutations map to the three "hot spots" - E542 K and E545 K in the helical (exon 9) and H1047R in the kinase (exon 20) domains of the p110alpha. These hot spot mutations lead to a gain of function in PI3 K signaling. We aimed to determine the frequency of PIK3CA mutations in the three most common Malaysian cancers. In this study, we assessed the genetic alterations in the PIK3CA gene in a series of 20 breast carcinomas, 24 colorectal carcinomas, 27 nasopharyngeal carcinomas (NPC), and 5 NPC cell lines. We performed mutation analysis of the PIK3CA gene by genomic polymerase chain reaction (PCR) and followed by DNA direct sequencing in exons 9 and 20. No mutations were detected in any of the 24 colorectal and 27 NPC samples, but one hot spot mutation located at exon 20 was found in a NPC cell line, SUNE1. Interestingly, PIK3CA somatic mutations were present in 6/20 (30%) breast carcinomas. Two of the six mutations, H1047R, have been reported previously as a hot spot mutation. Only one out of three hot spot mutations were identified in breast tumor samples. The remaining four mutations were novel. Our data showed that a higher incidence rate of PIK3CA mutations was present in Malaysian breast cancers as compared to colorectal and nasopharyngeal tumor tissues. Our findings also indicate that PIK3CA mutations play a pivotal role in activation of the PI3 K signaling pathway in breast cancer, and specific inhibitors of PIK3CA could be useful for breast cancer treatment in Malaysia.
    Matched MeSH terms: Nasopharyngeal Neoplasms/genetics; Nasopharyngeal Neoplasms/metabolism
  9. A high incidence of serum IgG antibodies to the Epstein-Barr virus replication activator protein in nasopharyngeal carcinoma
    Mathew A, Cheng HM, Sam CK, Joab I, Prasad U, Cochet C
    Cancer Immunol Immunother, 1994 Jan;38(1):68-70.
    PMID: 8299121
    The BamHI Z EBV replication activator (ZEBRA) protein is involved in the switch from latency to productive cycle of Epstein-Barr virus. A recombinant ZEBRA protein was synthesized and assessed in enzyme-linked immunosorbent assay (ELISA) for serum IgG response in nasopharyngeal carcinoma (NPC) patients. In 100 NPC serum samples that were positive for IgA to the EBV viral capsid antigen (VCA), 75% had IgG anti-ZEBRA antibodies. In contrast, only 3/83 (3.6%) serum samples from healthy donors and 2/50 (4%) from other cancers were positive for IgG to ZEBRA. Interestingly, in a selected group of 100 NPC sera negative for IgA to VCA, 25% contained IgG anti-ZEBRA antibodies. This suggests that the ELISA for IgG anti-ZEBRA may also identify earlier cases of NPC not detected by the conventional immunofluorescence test for IgA to VCA.
    Matched MeSH terms: Nasopharyngeal Neoplasms/immunology*
  10. Linear epitopes of the replication-activator protein of Epstein-Barr virus recognised by specific serum IgG in nasopharyngeal carcinoma
    Cheng HM, Foong YT, AbuSamah AJ, Dillner J, Sam CK, Prasad U
    Cancer Immunol Immunother, 1995 Apr;40(4):251-6.
    PMID: 7750123
    The linear antigenic epitopes of the Epstein-Barr virus replication activator protein (ZEBRA), recognised by specific serum IgG in nasopharyngeal carcinoma (NPC), were determined. This was achieved by synthesizing the entire amino acid sequence of ZEBRA as a set of 29, 22-residue peptides with an overlap of 14 amino acids. The ZEBRA peptides were tested in enzyme-linked immunosorbent assay (ELISA) for IgG binding in sera from 37 selected NPC patients who had IgG antibodies to the native ZEBRA protein. The most immunogenic epitope was peptide 1 at the amino-terminal end with 36 of the sera reactive against it. Further analysis of peptide 1, using the multipin peptide-scanning technique, defined a 10-amino-acid sequence FTPDPYQVPF, which was strongly bound by IgG. Two other regions of ZEBRA were also identified as immunodominant IgG epitopes, namely peptide 11 (amino acids 82-103) and peptide 19/20 (amino acids 146-175) with 8-13 of the NPC sera reactive against the peptides. The number of peptides reactive with individual NPC serum varies from 1 to 6 or more and there is some correlation between a greater number of peptide (at least 4) bound and a higher (at least 1:40) titre of serum IgA to viral capsid antigen. The immunodominant ZEBRA peptide 1 could be utilised in IgG ELISA for the detection of NPC.
    Matched MeSH terms: Nasopharyngeal Neoplasms/immunology*; Nasopharyngeal Neoplasms/virology
  11. Activation of phosphatidylinositol 3-kinase/Akt signaling by EGF downregulates membranous E-cadherin and β-catenin and enhances invasion in nasopharyngeal carcinoma cells
    Yip WK, Seow HF
    Cancer Lett, 2012 May 28;318(2):162-72.
    PMID: 22182447 DOI: 10.1016/j.canlet.2011.12.018
    Dysregulation of E-cadherin and β-catenin function in cell-cell adhesion is common in nasopharyngeal carcinoma (NPC) and correlates with metastatic disease. In this study, we examined the role of EGF-activated phosphatidylinositol 3-kinase (PI3K)-Akt signaling in E-cadherin and β-catenin regulation. We found that reduced membranous E-cadherin and β-catenin expression was positively correlated with Akt phosphorylation in NPC tissues. EGF treatment disrupted cell-cell adhesion and resulted in mesenchymal morphological features in NPC cell lines (TW01, TW04, and TW06). Western blot analysis showed that the E-cadherin protein level was partially reduced in TW04 cells only and the β-catenin levels were not considerably affected upon EGF treatment. In contrast, quantitative real-time RT-PCR showed that the E-cadherin, but not β-catenin, mRNA levels were markedly reduced by EGF in all cell lines. Immunofluorescent staining revealed that E-cadherin and β-catenin appeared to be markedly reduced on the cell surface and more localized in the cytoplasm. Inhibition of PI3K by LY294002 did not abolish the EGF-induced downregulation of E-cadherin protein or mRNA in TW04 cells but moderately increased the β-catenin protein level in TW01 cells and mRNA level in TW06 cells. However, LY294002 substantially restored or increased cell surface E-cadherin and β-catenin in all EGF-treated cell lines, in concordance with the inhibition of cell morphological changes. Moreover, LY294002 significantly blocked EGF-driven cell invasion, correlating with the elevation of membranous E-cadherin and β-catenin levels. In conclusion, EGF-induced epithelial-to-mesenchymal transition may not be only dependent on downregulation of E-cadherin protein/mRNA but also on mislocalization of E-cadherin and β-catenin. The mechanisms involved may be related, at least in part, to the PI3K-Akt pathway.
    Matched MeSH terms: Nasopharyngeal Neoplasms/enzymology; Nasopharyngeal Neoplasms/metabolism*; Nasopharyngeal Neoplasms/pathology
  12. Suppression of BCL-2 synergizes cisplatin sensitivity in nasopharyngeal carcinoma cells
    Low SY, Tan BS, Choo HL, Tiong KH, Khoo AS, Leong CO
    Cancer Lett, 2012 Jan 28;314(2):166-75.
    PMID: 22033244 DOI: 10.1016/j.canlet.2011.09.025
    The efficacy of cisplatin for treating nasopharyngeal carcinoma (NPC) is limited by the dose-related toxicities and the development of resistance to cisplatin. Recent studies have shown that B cell lymphoma-2 (BCL-2) is overexpressed and confers chemoresistance in NPC. Thus, targeted therapy against BCL-2 may enhance the antitumour effects of chemotherapy by sensitizing the tumor cells to undergo apoptosis. This study evaluated the combined effects of BCL-2 inhibition and cisplatin in NPC cells. Our results demonstrate that inhibition of BCL-2 by small-hairpin RNA (shRNA) or the BCL-2 inhibitor YC137, synergizes cisplatin sensitivity in NPC cells that overexpress BCL-2. We also show that YC137 enhance cisplatin-induced apoptosis in HK1 and CNE1 cells through suppression of BCL-2 protein expression, induction of mitochondrial depolarization and activation of caspase 9 and caspase 3/7. These findings suggest that the combination of BCL-2 inhibition and cisplatin represents a promising strategy for treating NPC.
    Matched MeSH terms: Nasopharyngeal Neoplasms/drug therapy*; Nasopharyngeal Neoplasms/pathology
  13. Parallel genome-wide RNAi screens identify lymphocyte-specific protein tyrosine kinase (LCK) as a targetable vulnerability of cell proliferation and chemoresistance in nasopharyngeal carcinoma
    Liew K, Yu GQS, Wei Pua LJ, Wong LZ, Tham SY, Hii LW, et al.
    Cancer Lett, 2021 Apr 28;504:81-90.
    PMID: 33587980 DOI: 10.1016/j.canlet.2021.02.006
    Despite recent in advances in the management of nasopharyngeal carcinoma (NPC), development of targeted therapy remains challenging particularly in patients with recurrent or metastatic disease. To search for clinically relevant targets for the treatment of NPC, we carried out parallel genome-wide functional screens to identified essential genes that are required for NPC cells proliferation and cisplatin resistance. We identified lymphocyte-specific protein tyrosine kinase (LCK) as a key vulnerability of both proliferation and cisplatin resistance. Depletion of endogenous LCK or treatment of cells with LCK inhibitor induced tumor-specific cell death and synergized cisplatin sensitivity in EBV-positive C666-1 and EBV-negative SUNE1 cells. Further analyses demonstrated that LCK is regulating the proliferation and cisplatin resistance through activation of signal transducer and activator of transcription 5 (STAT5). Taken together, our study provides a molecular basis for targeting LCK and STAT5 signaling as potential druggable targets for the management of NPC.
    Matched MeSH terms: Nasopharyngeal Neoplasms/drug therapy*; Nasopharyngeal Neoplasms/enzymology; Nasopharyngeal Neoplasms/pathology
  14. MRI-based brain structural changes following radiotherapy of Nasopharyngeal Carcinoma: A systematic review
    Voon NS, Lau FN, Zakaria R, Md Rani SA, Ismail F, Manan HA, et al.
    Cancer Radiother, 2021 Feb;25(1):62-71.
    PMID: 33414057 DOI: 10.1016/j.canrad.2020.07.008
    PURPOSE: Nasopharyngeal carcinoma (NPC) radiotherapy (RT) irradiates parts of the brain which may cause cerebral tissue changes. This study aimed to systematically review the brain microstructure changes using MRI-based measures, diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI) and voxel-based morphometry (VBM) and the impact of dose and latency following RT.

    METHODS: PubMed and Scopus databases were searched based on PRISMA guideline to determine studies focusing on changes following NPC RT.

    RESULTS: Eleven studies fulfilled the inclusion criteria. Microstructural changes occur most consistently in the temporal region. The changes were correlated with latency in seven studies; fractional anisotropy (FA) and gray matter (GM) volume remained low even after a longer period following RT and areas beyond irradiation site with reduced FA and GM measures. For dosage, only one study showed correlation, thus requiring further investigations.

    CONCLUSION: DTI, DKI and VBM may be used as a surveillance tool in detecting brain microstructural changes of NPC patients which correlates to latency and brain areas following RT.

    Matched MeSH terms: Nasopharyngeal Neoplasms/radiotherapy*
  15. Relationship between immunoglobulin allotypes and susceptibility to nasopharyngeal carcinoma in Malaysia
    Tarone RE, Levine PH, Yadav M, Pandey JP
    Cancer Res, 1990 Jun 1;50(11):3186-8.
    PMID: 1692255
    The relationship between immunoglobulin allotypes and risk of developing nasopharyngeal carcinoma was examined in a comparative study of 50 Chinese cases and 140 Chinese controls and 50 Malay cases and 79 Malay controls residing in Malaysia. Although the most common Gm phenotype was elevated in both Chinese and Malay nasopharyngeal carcinoma patients compared to their controls, there were no significant differences between cases and controls in the distribution of Gm haplotypes in either population. There were no differences between cases and controls in the distribution of Km alleles in either population. Thus a previously reported association of Km(1) with increased nasopharyngeal carcinoma risk in Tunisia is not confirmed in two Mongoloid populations in Malaysia.
    Matched MeSH terms: Nasopharyngeal Neoplasms/ethnology; Nasopharyngeal Neoplasms/immunology*
  16. Fulltext Salted fish and inhalants as risk factors for nasopharyngeal carcinoma in Malaysian Chinese
    Armstrong RW, Armstrong MJ, Yu MC, Henderson BE
    Cancer Res, 1983 Jun;43(6):2967-70.
    PMID: 6850606
    We conducted a case-control study of nasopharyngeal carcinoma among Malaysian Chinese to test inhalants, salted fish consumption, and use of tobacco, alcohol, and nasal ointments as risk factors for the disease. Interviews with 100 cases and 100 controls indicated that salted fish consumption during childhood was a significant risk factor (relative risk, 3.0; p = 0.04); childhood daily consumption of this food item compared to nonconsumption carried a relative risk of 17.4 [95% confidence interval = (2.7, 111.1)]. Occupational exposure to smokes (relative risk, 6.0; p = 0.006) and to dusts (relative risk, 4.0; p less than 0.001) was also significantly associated with nasopharyngeal carcinoma. The two risk factors (consumption of salted fish and exposure to smoke and/or dust) were independent of each other. There was no association between nasopharyngeal carcinoma and tobacco, alcohol, or nasal ointments.
    Matched MeSH terms: Nasopharyngeal Neoplasms/etiology*
  17. Fulltext Prevalence of Nasopharyngeal Carcinoma in Patients with Dermatomyositis: A Systematic Review and Meta-Analysis
    Irekeola AA, Shueb RH, E A R ENS, Wada Y, Abdul Rahman Z, Ahmad S, et al.
    Cancers (Basel), 2021 Apr 14;13(8).
    PMID: 33919987 DOI: 10.3390/cancers13081886
    For more than 50 years, nasopharyngeal carcinoma (NPC) has been associated with dermatomyositis (DM), a rare idiopathic inflammatory disorder that mainly affects the skin and muscles. Although the association between these rare diseases is well-documented, the actual prevalence of NPC in DM patients remains unknown. Here, a systematic review and meta-analysis of published data was conducted in accordance with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Electronic databases including PubMed, Scopus, ScienceDirect, and Google Scholar were searched without year or language restrictions for studies reporting the occurrence of NPC in DM patients. The study protocol was lodged with PROSPERO (CRD42021225335). A total of 95 studies covering 303 cases of NPC among 16,010 DM patients was included. Summary estimates were calculated using the random-effects model. The pooled prevalence of NPC in DM was 3.3% (95% CI, 2.5-4.3). When stratified according to study location, higher prevalence estimates were obtained for Hong Kong (36.5%), Malaysia (27.7%), and Singapore (11.9%). There was a predominance of cases among male DM patients compared with females, and most patients were aged 40 and above. Many of the NPC cases were found to be diagnosed after the diagnosis of DM. It is therefore pertinent to screen for NPC in DM patients, especially among older DM patients in the Asian region.
    Matched MeSH terms: Nasopharyngeal Neoplasms
  18. Fulltext Potential role of oxidative stress-induced apoptosis in mediating chromosomal rearrangements in nasopharyngeal carcinoma
    Tan SN, Sim SP, Khoo AS
    Cell Biosci, 2016;6:35.
    PMID: 27231526 DOI: 10.1186/s13578-016-0103-9
    Genetic aberrations have been identified in nasopharyngeal carcinoma (NPC), however, the underlying mechanism remains elusive. There are increasing evidences that the apoptotic nuclease caspase-activated deoxyribonuclease (CAD) is one of the players leading to translocation in leukemia. Oxidative stress, which has been strongly implicated in carcinogenesis, is a potent apoptotic inducer. Most of the NPC etiological factors are known to induce oxidative stress. Although apoptosis is a cell death process, cells possess the potential to survive apoptosis upon DNA repair. Eventually, the surviving cells may carry rearranged chromosomes. We hypothesized that oxidative stress-induced apoptosis may cause chromosomal breaks mediated by CAD. Upon erroneous DNA repair, cells that survive apoptosis may harbor chromosomal rearrangements contributing to NPC pathogenesis. This study focused on the AF9 gene at 9p22, a common deletion region in NPC. We aimed to propose a possible model for molecular mechanism underlying the chromosomal rearrangements in NPC.
    Matched MeSH terms: Nasopharyngeal Neoplasms
  19. Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles
    Yeong KY, Tan SC, Mai CW, Leong CO, Chung FF, Lee YK, et al.
    Chem Biol Drug Des, 2018 01;91(1):213-219.
    PMID: 28719017 DOI: 10.1111/cbdd.13072
    Both sirtuin and poly(ADP-ribose)polymerase (PARP) family of enzymes utilize NAD+ as co-substrate. Inhibitors of sirtuins and PARPs are important tools in drug discovery as they are reported to be linked to multiple diseases such as cancer. New potent sirtuin inhibitors (2,4,6-trisubstituted benzimidazole) were discovered from reported PARP inhibitor scaffold. Interestingly, the synthesized compounds have contrasting sirtuin and PARP-1 inhibitory activities. We showed that modification on benzimidazoles may alter their selectivity toward sirtuin or PARP-1 enzymes. This offers an opportunity for further discovery and development of new promising sirtuin inhibitors. Molecular docking studies were carried out to aid the rationalization of these observations. Preliminary antiproliferative studies of selected compounds against nasopharyngeal cancer cells also showed relatively promising results.
    Matched MeSH terms: Nasopharyngeal Neoplasms
  20. Inclusion bodies of recombinant Epstein-Barr virus capsid antigen p18 as potential immobilized antigens in enzyme immunoassays for detection of nasopharyngeal carcinoma
    Lim CS, Goh SL, Kariapper L, Krishnan G, Lim YY, Ng CC
    Clin Chim Acta, 2015 Aug 25;448:206-10.
    PMID: 26164385 DOI: 10.1016/j.cca.2015.07.008
    Development of indirect enzyme-linked immunosorbent assays (ELISAs) often utilizes synthetic peptides or recombinant proteins from Escherichia coli as immobilized antigens. Because inclusion bodies (IBs) formed during recombinant protein expression in E. coli are commonly thought as misfolded aggregates, only refolded proteins from IBs are used to develop new or in-house diagnostic assays. However, the promising utilities of IBs as nanomaterials and immobilized enzymes as shown in recent studies have led us to explore the potential use of IBs of recombinant Epstein-Barr virus viral capsid antigen p18 (VCA p18) as immobilized antigens in ELISAs for serologic detection of nasopharyngeal carcinoma (NPC).
    Matched MeSH terms: Nasopharyngeal Neoplasms/diagnosis*; Nasopharyngeal Neoplasms/immunology; Nasopharyngeal Neoplasms/virology*
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