Most nasopharyngeal carcinomas (NPCs) in a high-incidence population are driven by Epstein-Barr virus (EBV) infection. EBV-associated malignancies have increased expression of the programmed death-ligand 1 (PD-L1). Immunotherapy agents targeting the PD-1/PD-L1 pathway have achieved durable treatment effects in patients with various cancer types including EBV-associated malignancies. In this study, we sought to investigate PD-L1 expression in a cohort of patients with NPCs from the Philippines. Fifty-six NPCs were studied for PD-L1, p16, and DNA mismatch repair (MMR) deficiency by immunohistochemistry. One case with MMR deficiency was also assessed for microsatellite instability (MSI) by polymerase chain reaction. EBV and human papillomavirus (HPV) status were tested by in situ hybridization. All NPCs were p16 negative. Three of the 56 NPCs (5%) were EBV negative (EBV-) and HPV negative, while one NPC (1/56, 2%) was EBV positive and showed MSI (EBV?/MSI). Positive PD-L1 expression (PD-L1?), defined as membranous staining in C1% tumor cells, was seen in 64% (36/56) of NPCs. All three EBV-NPCs were PD-L1? as was the EBV?/MSI NPC. PD-L1? was seen significantly more often in NPCs from non-smokers than those from smokers (23/28, 82% vs 9/18, 50%; P = 0.047). PD-L1? was not associated with pT, pN, distant metastasis, or clinical stage (P [ 0.05). PD-L1? was not associated with overall survival (P = 0.473). In summary, our results show frequent PD-L1 expression in NPCs regardless of EBV status and a preferential PD-L1 expression in non-smokers. MSI and HPV positivity are exceedingly rare in NPCs.

mouse anti-canine FGF7 (1:50 dilution). Primary tenocyte culture and treatment conditions: FGF7 and Periostin are two proteins that correlate to FGF7 and POSTN genes. They were chosen to test their functional effects on canine FDP tenocyte biology. Tenocytes were classified into 4 groups: non-treated control group, FGF7 group, periostin group, and FGF7 with periostin group. Tenocyte proliferation assay: The cells were incubated with completed medium (DMEM supplemented with 10% FBS, control) containing 0.5ug/ml FGF7 and/or 1ug/ml Periostin. Images were captured by the Incucyte® Live-Cell Analysis System. Caspase-3/7 mediated apoptosis assay: The Incucyte ® Caspase-3/7 Green Dyes were diluted to 1:1000 in full culture medium. Cells were then treated with 0.5ug/ml FGF7 and/or 1ug/ml Periostin in MEM medium containing Caspase-3/7 Green Dyes. The Caspase-3/7 green apoptosis assay reagent had the ability to show green fluorescent staining of nuclear DNA after being cleaved by Caspase-3/7. RESULTS: Differentially expressed (17826) genes were screened in the chordae tendineae compared to the flexor tendon, among which, 1172 genes with significantly increased expression (log2 fold change > 2) and 547 with decreased expression (log2 fold change < 2). The 20 top up and down-regulated genes are noted. Moreover, we found that mRNA levels of POSTN and FGF7 were highly expressed in chordae tendineae, while almost no expression was observed in flexor tendon (P<.05). Immunohistochemical analyses also confirmed this finding. The caspase-3/7 apoptosis assay showed promising effects on anti-apoptosis of the proteins. CONCLUSIONS:This preliminary discovery promotes a novel idea for tenogenesis using specific molecules identified from chordae tendineae in the future.

No abstract