TLR9 activation induces immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, and metastasis and immunosuppression are responsible for the poor prognosis of OSCC. Previous studies have shown that poly(ADP-ribose) polymerase (PARP)1 plays a key role in the pathogenesis of OSCC. Therefore, PARP1 may serve as an important research target for the potential treatment of OSCC. Here, we aimed to investigate the role of PARP1 in the tumorigenesis of OSCC and elucidate the key molecular mechanisms of its upstream and downstream regulation in vivo and in vitro. In human OSCC tissues and cells, Toll-like receptor (TLR)9 and PD-L1 were highly expressed and PARP1 was lowly expressed. Suppression of TLR9 remarkably repressed CAL27 and SCC9 cell proliferation, migration, and invasion. After coculture, we found that low expression of TLR9 inhibited PD-L1 expression and immune escape. In addition, TLR9 regulated PD-L1 expression through the PARP1/STAT3 pathway. PARP1 mediated the effects of TLR9 on OSCC cell proliferation, migration, and invasion and immune escape. Additionally, in vivo experiments further verified that TLR9 promoted tumor growth and immune escape by inhibiting PARP1. Collectively, TLR9 activation induced immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in OSCC, providing important insights for subsequent in-depth exploration of the mechanism of OSCC.NEW & NOTEWORTHY In this research, we took PARP1 as the key target to explore its regulatory effect on oral squamous cell carcinoma (OSCC). The key molecular mechanisms involved in its upstream and downstream regulation were elucidated in OSCC cell lines in vitro and tumor-bearing mice in vivo, combined with clinical OSCC tissues.

5-aminolevulinic acid photodynamic therapy for extensive oral leukoplakia with concomitant oral submucous fibrosis: A case report.

BACKGROUND: Oral leukoplakia and oral submucous fibrosis are potentially malignant disorders of the oral cavity, with high rates of recurrence and malignant transformation. Notably, the malignant transformation rate of oral leukoplakia with concomitant oral submucous fibrosis is significantly higher than that of oral submucous fibrosis or oral leukoplakia alone. However, the management of these conditions is not well defined. Photodynamic therapy is a minimally invasive treatment modality that effectively targets oral potentially malignant disorders, such as oral leukoplakia, erythroleucoplakia, and verrucous hyperplasia, with the advantages of being repeatable and leaving no scarring. CASE PRESENTATION: We report the case of a 42-year-old man with concomitant oral leukoplakia and oral submucous fibrosis almost involving the entire right buccal mucosa, who underwent six sessions of topical 5-aminolevulinic acid-mediated photodynamic therapy. RESULTS: Photodynamic therapy successfully eradicated whitish plaques and improved mouth opening without any adverse effects. Although photodynamic therapy failed to completely reverse the pathological changes, grading of epithelial dysplasia did not progress and clinical recurrence was not found during the 10-month follow-up. CONCLUSION: In conclusion, topical 5-aminolevulinic acid-mediated photodynamic therapy appears safe and has excellent clinical efficacy against oral leukoplakia-concomitant oral submucous fibrosis, but long-term follow-up is necessary.

Deviation Analyses of Computer-Assisted, Template-Guided Mandibular Reconstruction With Combined Osteotomy and Reconstruction Pre-Shaped Plate Position Technology: A Comparative Study.

BACKGROUND: Computer-assisted and template-guided mandibular reconstruction provides higher accuracy and less variation than conventional freehand surgeries. The combined osteotomy and reconstruction pre-shaped plate position (CORPPP) technique is a reliable choice for mandibular reconstruction. This study aimed to evaluate the accuracy of CORPPP-guided fibular flap mandibular reconstruction and analyze the possible causes of the deviations. PATIENTS AND METHODS: From June 2015 to December 2016, 28 patients underwent fibular flap mandibular reconstruction. Virtual planning and personalized CORPPP-guided templates were applied in 15 patients while 13 patients received conventional freehand surgeries. Deviations during mandibulectomy and fibular osteotomy, and overall and triaxial deviation of the corresponding mandibular anatomical landmarks were measured by superimposing the pre- and postoperative virtual models. RESULTS: The deviation of the resection line and resection angle was 1.23 ± 0.98 mm and 4.11° ± 2.60°. The actual length of fibula segments was longer than the designed length in 7 cases (mean: 0.35 ± 0.32 mm) and shorter in 22 cases (mean: 1.53 ± 1.19 mm). In patients without ramus reconstruction, deviations of the ipsilateral condylar head point (Co.), gonion point (Go.), and coracoid process point (Cor.) were 6.71 ± 3.42 mm, 5.38 ± 1.71 mm, and 11.05 ± 3.24 mm in the freehand group and 1.73 ± 1.13 mm, 1.86 ± 0.96 mm, and 2.54 ± 0.50 mm in the CORPPP group, respectively, with significant statistical differences (p < 0.05). In patients with ramus reconstruction, deviations of ipsilateral Co. and Go. were 9.79 ± 4.74 mm vs. 3.57 ± 1.62 mm (p < 0.05), and 15.17 ± 6.53 mm vs. 4.36 ± 1.68 mm (p < 0.05) in the freehand group and CORPPP group, respectively. CONCLUSION: Mandibular reconstructions employing virtual planning and personalized CORPPP-guided templates show significantly higher predictability, convenience, and accuracy of mandibular reconstruction compared with conventional freehand surgeries. However, more clinical cases were required for further dimensional deviation analysis. The application and exploration of clinical practice would also continuously improve the design of templates.