Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma.

Radioresistance is one of the major factors that contributes to radiotherapy failure in oral cavity squamous cell carcinoma (OSCC). By comparing the prognostic values of 20,502 genes expressed in patients in The Cancer Genome Atlas (TCGA)-OSCC cohort with (n = 162) and without radiotherapy (n = 118), herein identified 297 genes positively correlated with poor disease-free survival in OSCC patients with radiotherapy as the potential radioresistance-associated genes. Among the potential radioresistance-associated genes, 36 genes were upregulated in cancerous tissues relative to normal tissues. The bioinformatics analysis revealed that 60S ribosomal protein L36a (RPL36A) was the most frequently detected gene involved in radioresistance-associated gene-mediated biological pathways. Then, two independent cohorts (n = 162 and n = 136) were assessed to confirm that higher RPL36A transcript levels were significantly associated with a poor prognosis only in OSCC patients with radiotherapy. Mechanistically, we found that knockdown of RPL36A increased radiosensitivity via sensitizing cells to DNA damage and promoted G2/M cell cycle arrest followed by augmenting the irradiation-induced apoptosis pathway in OSCC cells. Taken together, our study supports the use of large-scale genomic data for identifying specific radioresistance-associated genes and suggests a regulatory role for RPL36A in the development of radioresistance in OSCC.

Proteomic signatures of metronidazole-resistant Trichomonas vaginalis reveal novel proteins associated with drug resistance.

BACKGROUND: Trichomoniasis is the most common non-viral sexually transmitted disease caused by the protozoan parasite Trichomonas vaginalis. Metronidazole (MTZ) is a widely used drug for the treatment of trichomoniasis; however, increased resistance of the parasite to MTZ has emerged as a highly problematic public health issue. METHODS: We conducted iTRAQ-based analysis to profile the proteomes of MTZ-sensitive (MTZ-S) and MTZ-resistant (MTZ-R) parasites. STRING and gene set enrichment analysis (GESA) were utilized to explore the protein-protein interaction networks and enriched pathways of the differentially expressed proteins, respectively. Proteins potentially related to MTZ resistance were selected for functional validation. RESULTS: A total of 3123 proteins were identified from the MTZ-S and MTZ-R proteomes in response to drug treatment. Among the identified proteins, 304 proteins were differentially expressed in the MTZ-R proteome, including 228 upregulated and 76 downregulated proteins. GSEA showed that the amino acid-related metabolism, including arginine, proline, alanine, aspartate, and glutamate are the most upregulated pathways in the MTZ-R proteome, whereas oxidative phosphorylation is the most downregulated pathway. Ten proteins categorized into the gene set of oxidative phosphorylation were ATP synthase subunit-related proteins. Drug resistance was further examined in MTZ-S parasites pretreated with the ATP synthase inhibitors oligomycin and bafilomycin A1, showing enhanced MTZ resistance and potential roles of ATP synthase in drug susceptibility. CONCLUSIONS: We provide novel insights into previously unidentified proteins associated with MTZ resistance, paving the way for future development of new drugs against MTZ-refractory trichomoniasis.

[Retrospective study on postoperative complications and nursing measure for the oldest old patients receiving free flap reconstruction with head and neck cancers].

PURPOSE: To analyze the postoperative complications and nursing measures for the oldest old patients with head and neck cancer, who received free flap reconstruction. METHODS: A retrospective study for oldest old patients treated in the department of Oromaxillofacial Head and Neck Oncology of our hospital from 2005 to 2015 was conducted. All patients with head and neck cancer received free flap reconstruction with age≥85 years were selected. Demographics, clinical, nursing information and prognosis were collected. SPSS 17.0 software package was used for data analysis. RESULTS: There were a total of 24 oldest old patients, among whom 15 were male and 9 were female. The median age was 86 years old, 20 patients had co-morbidity, 18 patients had ASA Ⅱ and 6 patients had ASA Ⅲ. The median operation time was 420 minutes, while the median intraoperative blood loss was 550 mL. 16 patients underwent tracheotomy, 9 patients suffered from postoperative surgical complications and 16 patients experienced postoperative medical complications. CONCLUSIONS: The oldest old patients with head and neck cancer have high possibility of postoperative complications. Preoperative assessment, accurate postoperative observation and nursing measures can reduce the negative impact of postoperative complications and improve prognosis effectively.