Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidencebased medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

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We have shown that bone marrow (BM)-derived mesenchymal stem cells (BM-MSCs) from SLE patients exhibit senescent behavior and are involved in the pathogenesis of SLE. The aim of this study was to investigate the effects of rapamycin (RAPA) on the senescences and immunoregulatory ability of MSCs of MRL/lpr mice and SLE patients and the underlying mechanisms. Cell morphology, senescence associated β-galactosidase (SA-β-gal) staining, F-actin staining were used to detect the senescence of cells. BM-MSCs and purified CD4+ T cells were co-cultured indirectly. Flow cytometry was used to inspect the proportion of regulatory T (Treg) /T helper type 17 (Th17). We used small interfering RNA (siRNA) to interfere the expression of mTOR, and detect the effects by RT-PCR, WB and immunofluorescence. Finally, 1×106 of SLE BM-MSCs treated with RAPA were transplanted to cure the 8 MRL/lpr mice aged 16 weeks for 12 weeks. We demonstrated that RAPA alleviated the clinical symptoms of lupus nephritis and prolonged survival in MRL/lpr mice. RAPA reversed the senescent phenotype and improved immunoregulation of MSCs from MRL/lpr mice and SLE patients through inhibition of the mTOR signaling pathway. Marked therapeutic effects were observed in MRL/lpr mice following transplantation of BM-MSCs from SLE patients pretreated with RAPA.

Oncolytic adenoviruses, such as Delta-24-RGD, are replication-competent viruses that are genetically engineered to induce selective cancer cell lysis. In cancer cells, Delta-24-RGD induces massive autophagy, which is required for efficient cell lysis and adenoviral spread. Understanding the cellular mechanisms underlying the regulation of autophagy in cells treated with oncolytic adenoviruses may provide new avenues to improve the therapeutic effect. In this work, we showed that cancer cells infected with Delta-24-RGD undergo autophagy despite the concurrent activation of the AKT/mTOR pathway. Moreover, adenovirus replication induced sustained activation of JNK proteins in vitro. ERK1/1 phosphorylation remained unchanged during adenoviral infection, suggesting specificity of JNK activation. Using genetic ablation and pharmacological inactivation of JNK, we unequivocally demonstrated that cells infected with Delta-24-RGD required JNK activation. Thus, genetic co-ablation of JNK1 and JNK2 genes or inhibition of JNK kinase function rendered Delta-24-RGD–treated cells resistant to autophagy. Accordingly, JNK activation induced phosphorylation of Bcl-2 and prevented the formation of Bcl-2/Beclin 1 autophagy suppressor complexes. Using an orthotopic model of human glioma xenograft, we showed that treatment with Delta-24-RGD induced phosphorylation and nuclear translocation of JNK, as well as phosphorylation of Bcl-2. Collectively, our data identified JNK proteins as an essential mechanistic link between Delta-24-RGD infection and autophagy in cancer cells. Activation of JNK without inactivation of the AKT/mTOR pathway constitutes a distinct molecular signature of autophagy regulation that differentiates Delta-24-RGD adenovirus from the mechanism used by other oncolytic viruses to induce autophagy and provides a new rationale for the combination of oncolytic viruses and chemotherapy.

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