In this study, we tried to explore if xeroderma pigmentosum complementation group-A (XPA) expression is likely a prognostic prediction factor for locally advanced nasopharyngeal carcinoma (NPC) patients treated with platinum-based chemoradiotherapy, which was considered to bring chemotherapy-related severe toxicity compared with radiotherapy alone. Firstly, MTT assay revealed that downregulating XPA expression in NPC HONE1 and CNE1 cells decreased IC50 of cisplatin and sensitized cells to cisplatin. XPA expression was detected by immunohistochemistry in cancer tissues from locally advanced NPC patients treated with platinum-based chemoradiotherapy. The relationships between XPA expression and clinicopathologic features, overall survival and progression-free survival of patients were evaluated. The results showed that XPA expression was not associated with clinicopathologic parameters, but was likely an independent prognostic factor for patient survival. High XPA level predicts a poor prognosis, and the prediction values were higher in subgroups of younger, higher EBV antibody titer, or treated with concurrent chemoradiotherapy. Combining XPA levels and T/N classifications, we successfully classified these patients into low, medium and high risk groups for platinum-based chemoradiotherapy. These findings suggest that XPA levels may be a potential predictor of prognosis in locally advanced NPC patients treated with platinum-based chemoradiotherapy, and helpful for selecting patients likely to need and benefit from this treatment in future.

BackgroundInterferon-γ (IFN-γ) is regarded as a potent antitumor agent, but its clinical application is limited by its short half-life and significant side effects. In this paper, we tried to develop IFN-γ gene therapy by a replication defective adenovirus encoding the human IFN-γ (Ad-IFNγ), and evaluate the antitumoral effects of Ad-IFNγ on nasopharyngeal carcinoma (NPC) cell lines in vitro and in xenografts model.MethodsThe mRNA levels of human IFN-γ in Ad-IFNγ-infected NPC cells were detected by reverse transcription-polymerase chain reaction (RT-PCR), and IFN-γ protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in the culture supernatants of NPC cells and tumor tissues and bloods of nude mice treated with Ad-IFNγ. The effects of Ad-IFNγ on NPC cell proliferation was determined using MTT assay, cell cycle distribution was determined by flow cytometry analysis for DNA content, and cells apoptosis were analyzed by Annexin V-FITC/7-AAD binding assay and hoechst 33342/PI double staining. The anti-tumor effects and toxicity of Ad-IFNγ were evaluated in BALB/c nude mice carrying NPC xenografts.ResultsThe results demonstrated that Ad-IFNγ efficiently expressed human IFN-γ protein in NPC cell lines in vitro and in vivo. Ad-IFNγ infection resulted in antiproliferative effects on NPC cells by inducing G1 phase arrest and cell apoptosis. Intratumoral administration of Ad-IFNγ significantly inhibited the growth of CNE-2 and C666-1 cell xenografts in nude mice, while no significant toxicity was observed.ConclusionsThese findings indicate IFN-γ gene therapy mediated by replication defective adenoviral vector is likely a promising approach in the treatment of nasopharyngeal carcinoma.

2021) Β-Cyclodextrin-graftpoly(amidoamine) dendrons as the nitric oxide deliver system for the chronic rhinosinusitis therapy,

Due to the increasing incidence of tumor metastasis and multidrug resistance, even though a combined use of chemotherapy and radiotherapy is introduced, the 5-year average survival rate of an advanced nasopharyngeal carcinoma (NPC) patient still remains low. Hence, targeted slow-release anticancer drugs represent a potential therapy for advanced NPC. In this study, pH and redox dual stimulation-responsive folate-targeted folic acid -β-cyclodextrin -hyperbranched poly(amido amine)s (FA-DS-PAAs) nanocarriers for codelivery of docetaxel (DOC) and tissue factor pathway inhibitor 2 (TFPI-2) for NPC therapy are discussed. Physical and chemical properties, in vitro DOC-release properties, folic acid (FA)targeting, transfection, Western blotting, DOC and TFPI-2 codelivery, therapeutic properties, targeted inhibition, and biocompatibility, in vivo FA-targeting, toxicity, and therapeutic properties of FA-DS-PAAs/DOC/TFPI2 nanoparticles are evaluated. The results indicate that the 200 nm low-toxicity FA-DS-PAAs/DOC/TFPI2 nanoparticles could enhance TFPI2 gene expression, make cancer cells more sensitive to DOC, induce cell apoptosis, and reduce cell invasion more effectively compared with monochemotherapy. With respect to the targeted release of drugs (DOC and TFPI2) in tumor cells, FA-DS-PAAs/DOC/TFPI2 is associated with the slowest growth rate of tumor and the smallest volume of tumor, so this study demonstrates the best synergetic antitumor effect. We anticipate that this study is important because it not only provides a potential new therapy approach for NPC but also paves the preclinical way for potential application of FA-DS-PAAs/DOC/ TFPI2.