Comprehensive Analyses of Intraoral Benign and Malignant Nerve Sheath Tumors: The Rare Disease Entities Revisited.

INTRODUCTION: Intraoral benign and malignant nerve sheath tumors (BNST and MNST) are rare tumors with non-specific clinical presentations and represent diagnostic and therapeutic challenges. Current knowledge regarding their demographic, clinicopathological features and treatments remains fragmented. MATERIALS AND METHODS: The original data about patients diagnosed as intraoral BNST and MNST were retrieved from our disease registry (2005-2017). Comprehensive reviews of English and Chinese literature were performed to collect and analyze the epidemiological, clinicopathological data and treatment outcomes about those published cases. RESULTS: Thirty-four intraoral BNSTs were found at our institution in the past 13 years. Literature reviews identified 354 intraoral BNSTs in 223 articles and 60 intraoral MNSTs in 50 articles. Most intraoral BNSTs and MNSTs were presented in the second to fifth decade of life. Males outnumbered females in MNSTs, while BNSTs displayed a slight female preponderance. The common sites for intraoral BNSTs were parapharyngeal space followed by tongue, whereas mandible was the most common site for MNSTs. Most intraoral BNSTs were presented as slow-growing, painless mass or swelling, while MNSTs usually appeared as painful and invasive mass with discomfort. Surgical excision was preferred for intraoral BNSTs with excellent prognosis. Complete resection was indicated for intraoral MNST with dismal prognosis as evidenced by much recurrence, metastasis, and death. CONCLUSION: Intraoral BNST and MNST are rare diseases which should not be ignored when intraoral painless or painful mass/swelling is found. Surgical excision is indicated for intraoral BNST with favorable outcomes. However, further investigations are warranted to optimize the treatment for intraoral MNST to improve its prognosis.

Effect of verbascoside on apoptosis and metastasis in human oral squamous cell carcinoma.

Despite significant advances in therapy, the 5-year survival rates for patients with advanced stage oral cancers still remains poor as an appropriate treatment has not been found yet, due to side effects of chemo/radiotherapy. Verbascoside (VB), a major bioactive constituent of the Tsoong herb, displays pharmacological properties by exhibiting anti-oxidative, anti-inflammatory and anti-cancer activities. However, the underlining function and mechanism of VB in human oral squamous cell carcinoma (OSCC) remains unclear. In this study, we show that VB significantly decreased the viability and metastasis of HN4 and HN6 tumor cells, while promoting apoptosis. A xenograft OSCC mouse model further showed that intraperitoneal injection of VB strongly inhibited growth and lung metastasis of implanted tumor cells. Immunoblot analysis confirmed that VB effectively suppressed nuclear factor (NF)-κB activation and downstream Bcl-2/Bcl-XL expression, resulting in increased OSCC cell apoptosis. In addition, VB suppressed mRNA and protein expression of matrix metalloproteinase-9 via suppression of NF-κB activation, thereby inhibiting tumor cell metastasis. Inspiringly, compared to cisplatin-treated group, VB is a biocompatible agent without signficant side effects in vivo. Collectively, our results demonstrate that VB effectively inhibits OSCC tumor cell growth and metastasis via suppression of IκB kinase complex (IKK)/NF-κB-related signaling activation, suggesting that VB has potential use as a potent anticancer agent in OSCC therapeutic strategies.

Suppurative Temporomandibular Arthritis Caused by Chronic Suppurative Otitis Media: A Case Report.

The clinical diagnosis and treatment, including information such as age, history, clinical symptoms, signs, audiology, imaging examination, mode of operation, and postoperative follow-up, of a patient with suppurative temporomandibular arthritis caused by chronic suppurative otitis media were analyzed. As conservative drug treatment and drainage surgery were ineffective, the patient was treated with microscopic open radical mastoidectomy, tympanoplasty, the plasty of the cavity of auricular concha, facial nerve decompression, coarctation of the mastoid cavity combined with otoendoscpic resection of the lower temporomandibular lesions, and standard anti-inflammatory treatment after surgery. The patient appeared to be cured at the 3-month follow-up. The ear canal was dry, without any preauricular swelling, purulent ear discharge, otalgia, limitation of mouth opening, or other symptoms. A clear diagnosis by defining the scope of the lesions, analysis of the transmission route of the lesions, and standard conservative treatment, local drainage, and surgical resection, if necessary, are recommended for patients with suppurative temporomandibular arthritis.

Induction of autophagy protects human dental pulp cells from lipopolysaccharide-induced pyroptotic cell death.

The NOD-like receptor protein 3/caspase-1 inflammasome can be activated in human dental pulp tissue and fibroblasts; however, the underlying mechanisms are poorly understood. In the present study, lipopolysaccharide (LPS) was used to treat dental pulp cells to establish an inflammation model. Cell viability was examined by sulforhodamine B assay. Interleukin (IL)-1ß, caspase-1, microtubule-associated protein-1 light chain 3-II/I and p62 were determined by western blotting and ELISA. The phosphorylation (p-) levels of NF-κB and NF-κB inhibitor (IκB)α protein were observed by western blotting. The results demonstrated that LPS induced pyroptotic cell death in cultured dental pulp cells, which was supported by the increased levels of IL-1ß, IL-18 and caspase-1. Rapamycin and 3-methyladenine (3-MA) were used to activate and inhibit autophagy, and it was observed that LPS increased autophagy and rapamycin reduced LPS-induced dental pulp cell pyroptosis. However, 3-MA aggravated LPS-induced dental pulp cell pyroptosis. In addition, LPS inhibited the expression of IκBα, but increased the expression of p-NF-κB. Compared with the LPS group, 3-MA further inhibited the expression of IκBα but promoted the expression of p-NF-κB. However, rapamycin produced the opposite results to LPS. Under LPS treatment, the NF-κB pathway inhibitor BAY11-7082 further enhanced the inhibitory effects of rapamycin, but inhibited the promoting effects of 3-MA on the protein expression levels of IL-1ß and caspase-1. The results of the present study demonstrated that there is an important crosstalk between autophagy, pyroptosis and the NF-κB pathway, and that the modulation of pyroptosis in dental pulp cells may be a promising strategy to pulpitis therapy.

Blockade of LGR4 inhibits proliferation and odonto/osteogenic differentiation of stem cells from apical papillae.

During tooth root development, stem cells from apical papillae (SCAPs) are indispensable, and their abilities of proliferation, migration and odontoblast differentiation are linked to root formation. Leucine-rich repeat-containing GPCR 4 (LGR4) modulates the biological processes of proliferation and differentiation in multiple stem cells. In this study, we showed that LGR4 is expressed in all odontoblast cell lineage cells and Hertwig's epithelial root sheath (HERS) during the mouse root formation in vivo. In vitro we determined that LGR4 is involved in the Wnt/ß-catenin signaling pathway regulating proliferation and odonto/osteogenic differentiation of SCAPs. Quantitative reverse-transcription PCR (qRT-PCR) confirmed that LGR4 is expressed during odontogenic differentiation of SCAPs. CCK8 assays and in vitro scratch tests, together with cell cycle flow cytometric analysis, demonstrated that downregulation of LGR4 inhibited SCAPs proliferation, delayed migration and arrested cell cycle progression at the S and G2/M phases. ALP staining revealed that blockade of LGR4 decreased ALP activity. QRT-PCR and Western blot analysis demonstrated that LGR4 silencing reduced the expression of odonto/osteogenic markers (RUNX2, OSX, OPN, OCN and DSPP). Further Western blot and immunofluorescence studies clarified that inhibition of LGR4 disrupted ß-catenin stabilization. Taken together, downregulation of LGR4 gene expression inhibited SCAPs proliferation, migration and odonto/osteogenic differentiation by blocking the Wnt/ß-catenin signaling pathway. These results indicate that LGR4 might play a vital role in SCAPs proliferation and odontoblastic differentiation.

Polyethylene glycol-poly(ε-benzyloxycarbonyl-l-lysine)-conjugated VEGF siRNA for antiangiogenic gene therapy in hepatocellular carcinoma.

A polyethylene glycol-poly(ε-benzyloxycarbonyl-l-lysine) (PEG-SS-PLL) block copolymer based on a disulfide-linked, novel biodegradable catiomer bearing a PEG-sheddable shell was developed to avoid "PEG dilemma" in nanoparticle intracellular tracking of PEG-PLL where PEG was nondegradable. However, PEG-SS-PLL catiomers have not been used to deliver small interfering VEGF RNA (siVEGF) in antiangiogenesis gene therapy. In this study, we aimed to investigate whether this novel biodegradable catiomer can deliver siVEGF into cancer cells and at the same time have an antitumor effect in a xenograft mouse model. It was found that PEG-SS-PLL efficiently delivered siVEGF with negligible cytotoxicity, and significantly decreased the expression of VEGF at both the messenger-RNA and protein levels both in vitro and in vivo, and thus tumor growth was inhibited. Our findings demonstrated that PEG-SS-PLL/siVEGF could potentially be applied to antiangiogenesis gene therapy for hepatocellular carcinoma.