Transformation Of Nasopharyngeal Epithelial Cells Research Articles

Advance in integrating platinum-based chemotherapy with radiotherapy for locally advanced nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant tumor characterized by the malignant transformation of nasopharyngeal epithelial cells. It is highly sensitive to radiation therapy, making radiotherapy the primary treatment modality. However, 60-80% of patients are initially diagnosed with locally advanced NPC (LA-NPC), where radiotherapy alone often fails to achieve desirable outcomes. Therefore, combining radiotherapy with chemotherapy has emerged as an effective strategy to optimize treatment for LA-NPC patients. Among the various chemotherapy regimens, concurrent chemoradiotherapy (CCRT) using platinum-based drugs has been established as the most commonly utilized approach for LA-NPC patients. The extensive utilization of platinum drugs in clinical settings underscores their therapeutic potential and emphasizes ongoing efforts in the development of novel platinum-based complexes for anticancer therapy. The aim of this review is to elucidate the remarkable advances made in the field of platinum-based therapies for nasopharyngeal carcinoma, emphasizing their transformative impact on patient prognosis.

Targeting the crosstalk of epigenetic modifications and immune evasion in nasopharyngeal cancer.

Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer that is highly associated with Epstein-Barr virus (EBV) infection. EBV acts as an epigenetic driver in NPC tumorigenesis, reprogramming the viral and host epigenomes to regulate viral latent gene expression, and creating an environment conducive to the malignant transformation of nasopharyngeal epithelial cells. Targeting epigenetic mechanisms in pre-clinical studies has been shown promise in eradicating tumours and overcoming immune resistance in some solid tumours. However, its efficacy in NPC remains inclusive due to the complex nature of this cancer. In this review, we provide an updated understanding of the roles of epigenetic factors in regulating EBV latent gene expression and promoting NPC progression. We also explore the crosstalk between epigenetic mechanisms and immune evasion in NPC. Particularly, we discuss the potential roles of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors in reversing immune suppression and augmenting antitumour immunity. Furthermore, we highlight the advantages of combining epigenetic therapy and immune checkpoint inhibitor to reverse immune resistance and improve clinical outcomes. Epigenetic drugs have the potential to modulate both epigenetic mediators and immune factors involved in NPC. However, further research is needed to fully comprehend the diverse range of epigenetic modifications in NPC. A deeper understanding of the crosstalk between epigenetic mechanisms and immune evasion during NPC progression is crucial for the development of more effective treatments for this challenging disease.

Epstein-Barr virus infection mediated TP53 and Bcl-2 expression in nasopharyngeal carcinoma pathogenesis.

Epstein Barr virus (EBV) stimulates neoplastic transformation of nasopharyngeal epithelial cells through various molecular mechanisms, predominantly affecting inactivation of tumor-suppressor genes and activation of oncogenes. EBV infection is a major risk factor for nasopharyngeal carcinoma (NPC), yet its role in the carcinogenesis is not clear. EBV infection alters the expression of antiapoptotic proteins and tumor suppressor proteins. Therefore, this study investigated the correlation between EBV infection status with B cell lymphoma-2 (Bcl-2) and TP53 protein expression amongst laryngeal and nasopharyngeal cancer cases. This study was performed using 22 nasopharyngeal and 11 laryngeal cancer cases. EBV infection status, TP53 and Bcl-2 protein expression was studied using immunohistochemistry. The majority of the laryngeal cancer cases exhibited a poor prognosis and presented low Bcl-2 expression. A total of 22.7% cases were infected with EBV in the NPC cases. Upregulated TP53 expression was associated with EBV infection in the NPC cohort, and EBV infection was correlated with TP53 upregulation in the patients with NPC, suggesting mutual regulation between TP53 and EBV.

Epstein-Barr Virus-Encoded Latent Membrane Protein 1 Impairs G2 Checkpoint in Human Nasopharyngeal Epithelial Cells through Defective Chk1 Activation

Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, particularly in southern regions of China. EBV infection is closely associated with NPC and has long been postulated to play an etiological role in the development of NPC. However, the role of EBV in malignant transformation of nasopharyngeal epithelial cells remains enigmatic. The current hypothesis of NPC development is that premalignant nasopharyngeal epithelial cells harboring genetic alterations support EBV infection and expression of EBV genes induces further genomic instability to facilitate the development of NPC. The latent membrane protein 1 (LMP1) is a well-documented EBV-encoded oncogene. The involvement of LMP1 in human epithelial malignancies has been implicated, but the mechanisms of oncogenic actions of LMP1, particularly in nasopharyngeal cells, are unclear. Here we observed that LMP1 expression in nasopharyngeal epithelial cells impaired G2 checkpoint, leading to formation of unrepaired chromatid breaks in metaphases after γ-ray irradiation. We further found that defective Chk1 activation was involved in the induction of G2 checkpoint defect in LMP1-expressing nasopharyngeal epithelial cells. Impairment of G2 checkpoint could result in loss of the acentrically broken chromatids and propagation of broken centric chromatids in daughter cells exiting mitosis, which facilitates chromosome instability. Our findings suggest that LMP1 expression facilitates genomic instability in cells under genotoxic stress. Elucidation of the mechanisms involved in LMP1-induced genomic instability in nasopharyngeal epithelial cells will shed lights on the understanding of role of EBV infection in NPC development.

Possible transformation of nasopharyngeal epithelial cells in culture with Epstein-Barr virus from B95-8 cells

Explants of fresh biopsy specimens from non-neoplastic nasopharyngeal (NP) mucosa, nasopharyngeal carcinoma (NPC), other tumours (OT) of the head and neck and freshly removed tonsils were treated with an Epstein-Barr virus (EBV) preparation from B95-8 cells and cultured. The mainly epitheloid outgrowths from these infected explants were then compared with those from their respective uninfected controls at 14 days. Growth stimulation occurred with a significantly higher frequency, and the degree of stimulation was generally higher with the infected NP explants than those of the similarly infected explants of other origins. Furthermore, after treatment with the virus preparation, several of the outgrowths from the NP explants showed growth characteristics and cellular morphology typical of those of transformed cells. Light microscopy has shown the changed NP cells to have epithelial characteristics. This is now being verified by electron microscopy, which has so far shown the presence of keratin fibrils and desmosomes in one specimen examined. They are also being examined for the presence of EBV-DNA and EBNA, and other features of transformation, including malignant tendency, by passage through athymic nude mice.