Efficacy and safety of thalidomide in preventing oral mucositis in patients with nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy: A multicenter, open-label, randomized controlled trial.

BACKGROUND: This multicenter clinical trial was designed to evaluate the efficacy and safety of thalidomide (THD) in preventing oral mucositis (OM) in patients with nasopharyngeal carcinoma (NPC) undergoing concurrent chemoradiotherapy (CCRT). METHODS: Patients with locally advanced NPC were randomly assigned to either a THD group or a control group. All 160 patients received radical intensity-modulated radiotherapy plus cisplatin-based concurrent chemotherapy and basic oral hygiene guidance. Patients in the THD group received additional THD at the beginning of CCRT. The primary end points were the latency period and the incidence of OM. The secondary end points were mouth and throat soreness (MTS), weight loss, short-term efficacy, and adverse events. RESULTS: The median latency period of OM was 30 and 14 days in the THD and control groups, respectively (hazard ratio, 0.32; 95% confidence interval, 0.23-0.35; P < .0001). The incidence of OM and severe OM (World Health Organization grade 3 or higher) was significantly lower in the THD group than the control group (87.5% vs 97.5% [P = .016] and 27.5% vs 46.3% [P = .014], respectively). THD treatment also remarkably reduced the intensity of MTS and the degree of weight loss. In comparison with the control group, the incidence of nausea, vomiting, and insomnia was significantly decreased, whereas the incidence of dizziness and constipation was obviously increased in the THD group. The objective response rates 3 months after CCRT were similar between the groups. CONCLUSIONS: THD prolonged the latency period, reduced the incidence of OM, and did not affect the short-term efficacy of CCRT in patients with NPC. LAY SUMMARY: Oral mucositis is the most common complication of nasopharyngeal carcinoma during chemoradiotherapy; it decreases the patient's quality of life, and ideal mucosal protective agents are lacking. A few basic research and preclinical studies have shown that thalidomide may be an approach to ameliorating oral mucositis. The results of the current study confirm that thalidomide has a protective effect against oral mucositis in patients who have received chemoradiotherapy for nasopharyngeal carcinoma.

Administration of nimotuzumab combined with cisplatin plus 5-fluorouracil as induction therapy improves treatment response and tolerance in patients with locally advanced nasopharyngeal carcinoma receiving concurrent radiochemotherapy: a multicenter randomized controlled study.

BACKGROUND: Nimotuzumab (NTZ) is an anti-EGFR monoclonal antibody. However,the effect of targeted drugs combined with induction therapy in locally advanced nasopharyngeal carcinoma remains unclear. The aim of this study is to investigate the safety and efficacy of NTZ combined with cisplatin plus 5-fluorouracil (PF) as induction regimen in locally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent radiochemotherapy. METHODS: This was a multicenter randomized controlled study performed in eight Guangxi hospitals in 2015-2017. Eligible patients with NPC were randomized into nimotuzumab/PF (NPF group) and docetaxel/PF (DPF group) regimens, respectively, as induction therapy. After 2 cycles of induction therapy, all patients received cisplatin and concurrent intensity modulated radiation therapy (IMRT). Then, the two groups were compared for safety and efficacy. RESULTS: A total of 118 patients with stage III-IVa NPC were assessed, with 58 and 60 in the NPF and DPF groups, respectively. Compared with DPF treatment, NPF induction therapy showed a more pronounced effect on cervical lymph nodes (P = 0.036), with higher response rate (RR) (81% vs 60%). Compared with the DPF group, the NPF group showed significantly reduced leukopenia, neutropenia and gastrointestinal reactions (all P < 0.05); rash only appeared in the NPF group, but all cases were grade 1. During concurrent treatment with radiotherapy and chemotherapy, the NPF group showed better tolerance to radiotherapy and chemotherapy; neutropenia, anemia, gastrointestinal reactions, oral mucositis and radiation dermatitis in the NPF group were significantly reduced (P < 0.05). The expression rate of EGFR was 94.9% (112/118). Compared with the DPF group, patients with EGFR expression in the NPF group showed better response (77.8% vs 63.0%, P = 0.033). CONCLUSION: For locally advanced NPC patients receiving follow-up cisplatin and IMRT, nimotuzumab/PF for induction therapy has better lymph node response rate and milder adverse reactions than the DPF regimen. In addition, the patients have better tolerance in subsequent concurrent radiotherapy and chemotherapy; however, long-term efficacy needs further follow-up evaluation. TRIAL REGISTRATION: The registration number of the clinical trial is ChiCTR-OIC-16008201 and retrospectively registered on March 31, 2016.

Ferroptosis-Related Genes Are Associated with Radioresistance and Immune Suppression in Head and Neck Cancer.

Background: Ferroptosis is associated with tumor development; however, its contribution to radioresistant head and neck cancer (HNC) remains unclear. In this study, we used bioinformatics analysis and in vitro testing to explore ferroptosis-related genes associated with HNCs radiosensitivity. Materials and Methods: GSE9714, GSE90761, and The Cancer Genome Atlas (TCGA) datasets were searched to identify ferroptosis-related differentially expressed genes between radioresistant and radiosensitive HNCs or radiation-treated and nonradiation-treated HNCs. A protein-protein interaction analysis on identified hub genes was then performed. Receiver operating characteristic curves and Kaplan-Meier survival analysis were used to assess the diagnostic and prognostic potential of the hub genes. Cell counting kit-8, transwell assay, and flow cytometry were applied to examine the role of hub gene collagen type IV, alpha1 chain (COL4A1) on the proliferation, migration, invasion, and apoptosis of TU686 cells. Results: Hub genes MMP10, MMP1, COL4A1, IFI27, and INHBA showed diagnostic potential for HNC and were negatively correlated with overall survival and disease-free survival in the TCGA dataset. Also, IL-1B, IFI27, INHBA, and COL4A1 mRNA levels were significantly increased in TCGA patients with advanced clinical stages or receiving radiotherapy, whereas COL4A1, MMP10, and INHBA expressions were negatively correlated with immune infiltration. Furthermore, the knockdown of COL4A1 inhibited cell proliferation, migration, and invasion while promoting apoptosis in TU686 cells. Conclusion: Ferroptosis-related hub genes, such as COL4A1, are potential diagnostic and prognostic indicators as well as therapeutic targets for HNC.

ANTXR1 as a potential prognostic biomarker for hepatitis B virus-related hepatocellular carcinoma identified by a weighted gene correlation network analysis.

BACKGROUND: With high incidence and mortality rates, hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. Chronic hepatitis B virus (HBV) infection is a leading cause of HCC, especially for Asians and blacks. However, the molecular mechanisms underlying HBV-related HCC are unclear. This study sought to identify novel prognostic biomarkers and explore the potential pathogenesis of HBV-related HCC. METHODS: The gene expression profiles and corresponding clinical information of HCC from The Cancer Genome Atlas Liver Hepatocellular Carcinoma data set were analyzed by a weighted gene co-expression network analysis. Correlations between the co-expression modules and clinical traits were calculated. Next, key modules associated with HBV infection were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted for the genes in the key modules. The hub genes were identified based on the protein-protein interaction (PPI) network via the Cytoscape. Finally, an overall survival (OS) analysis was performed. RESULTS: The two modules (i.e., the brown and yellow modules) most relevant to HBV infection were constructed. A functional enrichment analysis revealed that the genes in the two modules were mainly enriched in HCC-related pathways, such as the phosphatidylinositol-3-kinase and protein kinase B signaling pathway, focal adhesion, human papillomavirus infection, the Rap1 signaling pathway, and the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. Ten hub genes [i.e., COL3A1, ANTXR1, COL14A1, THBS2, ADAMTS2, AEBP1, PRELP, EMILIN1, DCN and PODN] in the brown module, and 10 hub genes [i.e., USP34, SEC24C, ZNF770, STAG1, TSTD2, PKD1P6, CCNK, GFT2I, NT5C2 and SMG6] in the yellow module were identified. Among the hub genes, ANTXR1 (Anthrax-toxin receptor 1) was significantly correlated with HBV-related HCC patients' OS. CONCLUSIONS: ANTXR1 represents a potential therapeutic target for HBV-related HCC. This study offers novel insights into the molecular mechanisms of HBV-induced tumorigenesis, which needs to be further validated by basic experiments and large-scale cohort studies.

microRNA-9-5p regulates the mitochondrial function of hepatocellular carcinoma cells through suppressing PDK4.

Due to the lack of early diagnostic and effective treatment modalities, hepatocellular carcinoma (HCC) is still the most lethal cancer with a high mortality on a global scale. Recent studies have highlighted the key roles of microRNAs (miRs) in HCC development. In the study, we attempted to investigate the potential role of miR-9-5p in the progression of HCC. Expression of pyruvate dehydrogenase kinase 4 (PDK4) and miR-9-5p was examined in HCC tissues collected from HCC patients and cell lines. The proliferation, migration, invasion, and apoptosis of HCC cells, and levels of oxygen consumption rate, extracellular acidification rate and reactive oxygen species (ROS) as well as the tumorigenicity of transfected cells in vivo were measured after gain- and loss-of-function experiments in HCC cells. It was revealed that miR-9-5p was upregulated, while PDK4 was poorly expressed in HCC tissues and cells, associating with a poor prognosis of HCC patients. miR-9-5p directly targeted PDK4 and could downregulate its expression, thus leading to promoted cell proliferation, invasion and migration, enhanced mitochondrial activity and energy metabolism, and suppressed apoptosis in HCC cells, along with increased tumorigenicity in mouse xenograft models. Altogether, miR-9-5p facilitated mitochondrial energy metabolism of HCC cells by downregulating PDK4, promoting the development of HCC. miR-9-5p and PDK4 may serve as potential therapeutic targets for preventing recurrence and metastasis of HCC.