Down-regulation of DNA key protein-FEN1 inhibits OSCC growth by affecting immunosuppressive phenotypes via IFN-γ/JAK/STAT-1 / 国际口腔科学杂志·英文版

Oral squamous cell carcinoma (OSCC) escape from the immune system is mediated through several immunosuppressive phenotypes that are critical to the initiation and progression of tumors. As a hallmark of cancer, DNA damage repair is closely related to changes in the immunophenotypes of tumor cells. Although flap endonuclease-1 (FEN1), a pivotal DNA-related enzyme is involved in DNA base excision repair to maintain the stability of the cell genome, the correlation between FEN1 and tumor immunity has been unexplored. In the current study, by analyzing the clinicopathological characteristics of FEN1, we demonstrated that FEN1 overexpressed and that an inhibitory immune microenvironment was established in OSCC. In addition, we found that downregulating FEN1 inhibited the growth of OSCC tumors. In vitro studies provided evidence that FEN1 knockdown inhibited the biological behaviors of OSCC and caused DNA damage. Performing multiplex immunohistochemistry (mIHC), we directly observed that the acquisition of critical immunosuppressive phenotypes was correlated with the expression of FEN1. More importantly, FEN1 directly or indirectly regulated two typical immunosuppressive phenotype-related proteins human leukocyte antigen (HLA-DR) and programmed death receptor ligand 1 (PD-L1), through the interferon-gamma (IFN-γ)/janus kinase (JAK)/signal transducer and activator transcription 1 (STAT1) pathway. Our study highlights a new perspective on FEN1 action for the first time, providing theoretical evidence that it may be a potential immunotherapy target for OSCC.

Influence of magnification and superimposition of structures on cephalometric diagnosis

OBJECTIVE: The purpose of this study was to assess the influence of magnification and superimposition of structures on CBCT-generated lateral cephalometric radiographs (LCR) using different segments of the cranium. METHODS: CBCT scans of 10 patients were selected. Four LCR were generated using Dolphin Imaging(r) software: full-face, right side, left side and center of the head. A total of 40 images were imported into Radiocef Studio 2(r), and the angles of the most common cephalometric analyses were traced by the same observer twice and within a 10-day interval. Statistical analyses included intraexaminer agreement and comparison between methods by means of intraclass correlation coefficient (ICC) and Bland-Altman agreement tests. RESULTS: Intraexaminer agreement of the angles assessed by ICC was excellent (> 0.90) for 83% of measurements, good (between 0.75 and 0.90) for 15%, and moderate (between 0.50 and 0.75) for 2% of measurements. The comparison between methods by ICC was excellent for 68% of measurements, good for 26%, and moderate for 6%. Variables presenting wider confidence intervals (> 6o) in the Bland-Altman tests, in intraexaminer assessment, were: mandibular incisor angle, maxillary incisor angle, and occlusal plane angle. And in comparison methods the variables with wider confidence interval were: mandibular incisor, maxillary incisor, GoGn, occlusal plane angle, Frankfort horizontal plane (FHP), and CoA. CONCLUSION: Superimposition of structures seemed to influence the results more than magnification, and neither one of them significantly influenced the measurements. Considerable individual variability may occur, especially for mandibular and maxillary incisors, FHP and occlusal plane. .

OBJETIVO: o objetivo do presente estudo foi avaliar a influência da sobreposição estrutural e da magnificação nas radiografias cefalométricas laterais (RCL) geradas por meio de tomografias computadorizadas de feixe cônico (TCFC), usando diferentes segmentos do crânio. MÉTODOS: foram selecionadas 10 tomografias de pacientes. Quatro RCL foram geradas usando Dolphin Imaging, sendo face total, lado direito, lado esquerdo e o centro da cabeça. Um total de 40 imagens foi importado para o Radiocef Studio, e os ângulos das análises cefalométricas mais comuns foram medidos pelo mesmo observador, duas vezes, em um intervalo de 10 dias. As análises estatísticas incluíram concordância intraexaminador e comparação entre os métodos por meio do coeficiente de correlação intraclasse (ICC) e testes de concordância de Bland-Altman. RESULTADOS: a concordância intraexaminador dos ângulos avaliados pelo ICC foi excelente (> 0,90) para 83% das medições, boa (entre 0,75 e 0,90) para 15%, e moderada (entre 0,50 e 0,75) para 2% das medições. A comparação entre os métodos por ICC foi excelente para 68% das medições, boa para 26% e moderada para 6%. As variáveis que apresentaram intervalos de confiança mais amplos (> 6°) nos testes de Bland-Altman, na avaliação intraexaminador, foram: incisivo superior, incisivo inferior e plano oclusal, enquanto nos métodos de comparação, as variáveis com intervalos de confiança mais amplos foram: incisivo inferior, incisivo superior, GoGn, ângulo do plano oclusal, plano horizontal de Frankfort e CoA. CONCLUSÃO: a sobreposição estrutural pareceu influenciar os resultados mais do que a magnificação, mas os métodos não influenciaram significativamente as medições. Considerável variabilidade individual pode ocorrer especialmente para os incisivos superiores e inferiores, plano horizontal de Frankfort e plano oclusal. .