The impacts of weight loss on prognosis in nasopharyngeal carcinoma (NPC) remain unclear. The present study was therefore undertaken to investigate the association between critical weight loss and long-term survival in NPC patients. The eligible 2399 NPC patients were reviewed. Weight change was categorized into critical weight loss (CWL) and non-critical weight loss (Non-CWL). The associations of CWL with long-term survival were analyzed by Cox regression in the entire patient and two subsets. Propensity score matching was performed to reduce the effects of confounding factors. CWL was defined as body weight loss of ≥4.6 %. Compared with patients without CWL, patients with CWL had significantly lower 5-year OS (72.4 vs. 79.3 %, P < 0.001), FFS (71.1 vs. 78.4 %, P <0.001), and LR-FFS (78.1 vs. 84.8 %, P <0.001), respectively. After adjustment for potential confounders, CWL remained an independence prognostic factor for OS (HR = 1.352; 95 % CI 1.160–1.576; P < 0.001), FFS (HR = 3.275; 95 % CI 1.101–9.740; P = 0.033), and LR-FFS (HR = 6.620; 95 % CI 2.990–14.658; P < 0.001), respectively. Furthermore, subgroup analysis in the cohort of patients received concurrent chemoradiotherapy or radiotherapy alone confirmed the results in the entire patient even after the propensity-score matching. In IMRT cohort, CWL was also significantly associated with a lower OS (P = 0.04) and FFS (P = 0.04). CWL has a significant and independent impact on long-term survival in nasopharyngeal carcinoma patients.

The efficacy of PD-1 therapy in non-small cell lung cancer (NSCLC) patients remains unsatisfactory. Activating the STING pathway is a promising strategy to improve PD-1 inhibitor efficacy. Here, we found tetrandrine (TET), an anti-tumor compound extracted from a medicinal plant commonly used in traditional Chinese medicine, has the ability to inhibit NSCLC tumor growth. Mechanistically, TET induces nuclear DNA damage and increases cytosolic dsDNA, thereby activating the STING/TBK1/IRF3 pathway, which in turn promotes the tumor infiltration of dendritic cells (DCs), macrophages, as well as CD8⁺ T cells in mice. In vivo imaging dynamically monitored the increased activity of the STING pathway after TET treatment and predicted the activation of the tumor immune microenvironment. We further revealed that the combination of TET with αPD-1 monoclonal antibody (αPD-1 mAb) yields significant anti-cancer effects by promoting CD8⁺ T cell infiltration and enhancing its cell-killing effect, which in turn reduced the growth of tumors and prolonged survival of NSCLC mice. Therefore, TET effectively eliminates NSCLC cells and enhances immunotherapy efficacy through the activation of the STING pathway, and combining TET with anti-PD-1 immunotherapy deserves further exploration for applications.

The impact of standard chemo-radiotherapy (CRT) as preferred therapy for elderly patients (age≥60 years) with nasopharyngeal carcinoma (NPC) remains unclear. Therefore, a strict matched cohort study was conducted to compare the survival and treatment toxicity of standard chemo-radiotherapy in the elderly NPC patients with those of radiotherapy (RT) alone. From 1998 to 2003, total 498 newly diagnosed elderly non-metastatic NPC patients were abstracted and classified into two groups by the treatments they received. For each patient in the CRT group, a matched pair in RT group was identified by matching for gender, age, histological type, T and N classifications, RT dose to primary tumor and neck nodes, and days of radiotherapy. Treatment tolerability and toxicity were clarified, and treatment outcomes were calculated and compared between the two groups. Two groups were well balanced in clinical characteristics because of the strict matching conditions. Totally 87 pairs can be assessed according to the criteria. The 5-year OS, CSS, FFS, and LR-FFS for CRT and RT groups were 62% versus 40% (P=0.013), 67% versus 47% (P=0.018), 65% versus 53% (log-rank: P=0.064, Breslow: P=0.048), and 88% versus 72%, (P=0.019), respectively. There was no significant difference in 5-year D-FFS between the two groups (75% vs. 73%, P=0.456). The CRT group experienced significantly more Grade ≥3 acute mucositis (46.0% vs. 28.7%, P= 0.019). We concluded that standard chemo-radiotherapy can achieve a reasonable local and regional control in elderly NPC patients with acceptable and reversible acute toxicity. However, distant metastasis remains the dominant failure pattern. When the elderly NPC patients are in good performance status following a complete evaluation of overall functional status and comorbidity conditions, standard chemo-radiotherapy is worthy of recommendation.

Background: By regulating complex functional processes, circRNAs are crucial in the development of different cancers. Nevertheless, most circRNAs in papillary thyroid cancer metabolic reprogramming remain unknown. Methods: The expression of circRNA was assessed by qRT-PCR in papillary thyroid cancer tissues and cell lines. Cell proliferation and glucose intake experiments were performed by certain kit. Transwell assays and wound healing assays were performed to investigate the function of circRNA in metastasis. In addition, a serious of molecular experiments were conducted to determine the exact mechanism of circRAD18. Luciferase reporter and RNA immunoprecipitation assay were conducted to determine the molecular interaction between circRNA and miRNA. Results: We characterized circRAD18 as a significantly upregulated circRNA in papillary thyroid tissues and cell lines and found its downregulation could inhibit the growth and metastasis ability of papillary thyroid cancer. Interestingly, we found that circRAD18 was involved in glucose metabolism reprogramming of papillary thyroid cancer, and its silence could remarkably inhibit cell glucose uptake and lactate production in papillary thyroid cancer cells. Inhibition of circRAD18 could decrease the expression level of PDK1 protein by sponging miR-516b. Conclusions: This study verified the novel function of the circRAD18-miR-516b-PDK1 axis in papillary thyroid cancer metabolic reprogramming progression, which has potential to be a novel therapeutic target.