5‑Azacytidine treatment results in nuclear exclusion of DNA methyltransferase‑1, as well as reduced proliferation and invasion in human cytomegalovirus‑infected glioblastoma cells.

Glioblastoma (GBM) is the most aggressive form of brain tumor in adults, with a devastating outcome. Emerging evidence shows that human cytomegalovirus (HCMV) proteins and nucleic acids are present in GBM tissues. DNA methylation is important for the initiation and progression of cancer and is an established host response against invading nucleic acids.

A single nucleotide polymorphism in the Epstein-Barr virus genome is strongly associated with a high risk of nasopharyngeal carcinoma.

Background: Epstein-Barr virus (EBV) commonly infects the general population and has been associated with nasopharyngeal carcinoma (NPC), which has a high incidence in certain regions. This study aimed to address how EBV variations contribute to the risk of NPC.

Methods: Using logistic regression analysis and based on the sequence variations at EBV-encoded RPMS1, a multi-stage association study was conducted to identify EBV variations associated with NPC risk.

Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma.

Epigenetic silencing of tumor suppressor genes (TSGs) by promoter methylation can be an early event in the multi-step process of carcinogenesis. Human chromosome 3 contains clusters of TSGs involved in many cancer types including nasopharyngeal carcinoma (NPC), the most common cancer in Southern China. Among ten candidate TSGs identified in chromosome 3 using NotI microarray, ITGA9 and WNT7A could be validated.

Detection of nasopharyngeal carcinoma in Morocco (North Africa) using a multiplex methylation-specific PCR biomarker assay.

Background: Silencing of tumor suppressor genes (TSGs) or activation of oncogenes by, e.g., aberrant promoter methylation, may be early events during carcinogenesis.

Development of a multiplex methylation specific PCR suitable for (early) detection of non-small cell lung cancer.

Lung cancer is a worldwide health problem and a leading cause of cancer-related deaths. Silencing of potential tumor suppressor genes (TSGs) by aberrant promoter methylation is an early event in the initiation and development of cancer. Thus, methylated cancer type-specific TSGs in DNA can serve as useful biomarkers for early cancer detection.

Development of a non-invasive method, multiplex methylation specific PCR (MMSP), for early diagnosis of nasopharyngeal carcinoma.

Increasing evidence demonstrated that inactivation of tumor suppressor genes (TSGs) by aberrant promoter methylation is an early event during carcinogenesis. Aiming at developing early diagnostic or prognostic tools for various tumors, we took an EBV-associated tumor, nasopharyngeal carcinoma (NPC), as a model and developed a powerful assay based on "multiplex methylation specific-PCR (MMSP)". The MMSP assay was designed to detect tumor-specific methylation status of several NPC-related genes and was capable of acquiring multiplex information simultaneously through a single PCR reaction with the tiny tumor DNA derived from the direct body fluid close to the primary tumor.

Clinical significance of elevated spleen tyrosine kinase expression in nasopharyngeal carcinoma.

Background: Spleen tyrosine kinase (Syk) is a nonreceptor tyrosine kinase and often aberrantly expressed in human cancers. However, Syk expression pattern has not yet been investigated in nasopharyngeal carcinoma (NPC).

Methods: Samples of 223 NPC tissues were immunohistochemically stained for Syk expression and survival analysis was then performed.

A single nucleotide polymorphism in the matrix metalloproteinase 2 promoter is closely associated with high risk of nasopharyngeal carcinoma in Cantonese from southern China.

Matrix metalloproteinase 2 (MMP2) has been shown to play an important role in several steps of cancer development. The -1306C/T polymorphism of the MMP2 gene displays a strikingly lower promoter activity than the T allele, and the CC genotype in the MMP2 promoter has been reported to associate with the development of several cancers. To assess the contribution of the MMP2 -1306C/T polymorphism to the risk of nasopharyngeal carcinoma (NPC), we conducted a case-control study and analyzed MMP2 genotypes in 370 patients with NPC and 390 frequency-matched controls using real-time PCR-based TaqMan allele analysis.

Genomic DNA hypomethylation by histone deacetylase inhibition implicates DNMT1 nuclear dynamics.

Histone deacetylase inhibitors (HDACi) are promising antitumor drugs acting through reactivation of silenced tumor suppressor genes. Several HDACi are currently in clinical trials both for hematological and solid tissue malignancies. Cooperative action of HDACi and DNA methylation inhibitors (DNMTi) has been reported, making combined treatment an attractive choice for cancer therapy.

Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A.

The role of microRNA-155 (miR-155) has been associated with oncogenesis of several human tumors. However the expression pattern of miR-155 has not been investigated in nasopharyngeal carcinoma (NPC). The present study was to assess miR-155 expression pattern and its possible function in NPC, to identify its targets and evaluate their clinical applications in NPC.

Epstein-Barr virus genetic variation in Vietnamese patients with nasopharyngeal carcinoma: full-length analysis of LMP1.

Genetic variation in tumor virus genes and its impact on function might contribute to the understanding of geographic differences in risks for virus-associated tumors. This is particularly true for the genes known to contribute to the biology of the tumor. It is has been proposed that Epstein-Barr virus (EBV) gene variation has a role in the high risk of nasopharyngeal carcinoma (NPC) in South-East Asia.

A genome-wide scan suggests a susceptibility locus on 5p 13 for nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) occurs with high frequency in Southeast Asian populations. The high prevalence and familial clustering of NPC in these populations suggest that genetic factors may contribute to the increased cancer risk by affecting susceptibility. The aim of the present study was to map chromosomal loci linked to susceptibility genes predisposing for NPC.

Epstein-Barr virus-encoded LMP1 promotes cisplatin-induced caspase activation through JNK and NF-kappaB signaling pathways.

Our previous studies have shown that Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) potentiates chemotherapeutic agent-induced apoptosis in human cell lines of epithelial origin: cervical carcinoma-derived HeLa cells and nasopharyngeal carcinoma-derived TW03 cells. LMP1 acted upstream of caspase-dependent mitochondrial perturbation, and the effect was mapped to the C-terminal signaling domain of LMP1, designated CTAR2. CTAR2 is known to engage the c-Jun N-terminal kinase (JNK) and NF-kappaB pathways, and we show here that SP600125, a selective JNK inhibitor, suppresses LMP1 potentiation of cisplatin-induced mitochondrial damage and caspase activation in HeLa cells.

Polymorphisms of XRCC1 genes and risk of nasopharyngeal carcinoma in the Cantonese population.

Background: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China. In addition to environmental factors such as Epstein-Barr virus infection and diet, genetic susceptibility has been reported to play a key role in the development of this disease. The x-ray repair cross-complementing group 1 (XRCC1) gene is important in DNA base excision repair.

Comparison of Epstein-Barr virus DNA level in plasma, peripheral blood cell and tumor tissue in nasopharyngeal carcinoma.

Background: The plasma Epstein-Barr virus DNA (EBV-DNA) level has been found to be an indicator for staging and prognosis of nasopharyngeal carcinoma (NPC).

Materials And Methods: The EBV-DNA level in plasma, peripheral blood cells (PBC) and neoplastic tissues was quantitatively analyzed and potential associations with clinical parameters of NPC were investigated.

Results: The plasma EBV-DNA detecting rate and level in NPC (92%, 82,500 copies/ml) was significantly higher than that in NPC after treatment (19%, 0 copy/ml) and in controls (12%, 0 copy/ml) (p < 0.

Epstein-Barr virus LMP1 status in relation to apoptosis, p53 expression and leucocyte infiltration in nasopharyngeal carcinoma.

Background: Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) infection. EBV-encoded LMP1, expressed in most of NPC, has been suggested to have an important role in the pathogenesis and development of NPC and its expression correlates with poor prognosis.

Materials And Methods: Eighty-seven NPC biopsies were analyzed by immunohistochemistry for expression of markers of cell proliferation, apoptosis, infiltrating T lymphocytes and macrophages in relation to the LMP1 status.

V-val subtype of Epstein-Barr virus nuclear antigen 1 preferentially exists in biopsies of nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) has been suggested to be involved in pathogenesis of nasopharyngeal carcinoma (NPC). However, EBV infection is ubiquitous, whereas NPC occurs with strong geographic and racial distribution. Whether a substrain of EBV contributes to this phenomenon remains uncertain.

Characterization of a new SNP c767A/T (Arg222Trp) in the candidate TSG FUS2 on human chromosome 3p21.3: prevalence in Asian populations and analysis of association with nasopharyngeal cancer.

The FUS2 gene, encoding a novel cytoplasmic acetyltransferase, resides in the tumor suppressor gene region on human chromosome 3p21.3 and is considered a promising candidate tumor suppressor gene. We have identified a new single nucleotide polymorphism (SNP), c767A/T, in the coding region of the gene.

Comparison of plasma Epstein-Barr virus (EBV) DNA levels and serum EBV immunoglobulin A/virus capsid antigen antibody titers in patients with nasopharyngeal carcinoma.

Background: Serologic measurement of antibodies to Epstein-Barr virus (EBV) immunoglobulin A/viral capsid antigen (IgA/VCA) and early antigen (IgA/EA) has been used widely to screen for nasopharyngeal carcinoma (NPC) in China. Recently, it was found that plasma EBV DNA concentration is an indicator for the staging and prognosis of patients with NPC. To determine whether there is a correlation between plasma EBV DNA levels and serum levels of IgA/VCA, the authors measured both in patients with NPC and in a control group.

Apoptosis modulation of Epstein-Barr virus-encoded latent membrane protein 1 in the epithelial cell line HeLa is stimulus-dependent.

Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is required for viral transformation and has been shown to protect lymphocytes from apoptosis. However, the effect of LMP1 on cells of epithelial origin remains poorly understood. Using the epithelial cell line HeLa in which the expression of LMP1 is inducibly regulated by tetracycline, we demonstrate that apoptosis triggered by ligation of the death receptor, Fas, or by the chemotherapeutic agent, etoposide, is potentiated by LMP1.

High frequency loss of heterozygosity on the long arms of chromosomes 13 and 14 in nasopharyngeal carcinoma in Southern China.

Objective: To investigate the loss of heterozygosity (LOH) on chromosomal arms 13q and 14q in nasopharyngeal carcinoma (NPC) using 21 microsatellite polymorphic markers and to study whether there is a correlation between LOH and clinicopathologic parameters and/or Epstein-Barr virus (EBV) infection in NPC.

Methods: Sixty cases of NPC were studied using polymerase chain reaction based microsatellite analysis with genescan and genotyping techniques.

Results: LOH was detected on 13q in 78% of NPC tumors, high frequency LOH loci (more than 30%) clustered to 13q12.