Antitumorigenic Effect of Hsp90 Inhibitor SNX-2112 on Tongue Squamous Cell Carcinoma is Enhanced by Low-Intensity Ultrasound.

PURPOSE: The novel Hsp90 inhibitor SNX-2112 showed broad antitumor activity. However, it was still necessary to optimize the therapeutic dosage of SNX-2112 applied on tumors to obtain effective therapy with minimal dose to reduce toxicity. We investigated the role of low-intensity US in promoting antitumorigenic effect of low doses of SNX-2112 on tongue squamous cell carcinoma. METHODS: Cell viability was measured using CCK-8 assay or staining with Calcein AM/PI. Relative cumulative levels of SNX-2112 in cells were detected using high-performance liquid chromatography. The production of ROS was analyzed using fluorescence microscope and flow cytometer. Cellular apoptosis was detected using flow cytometer. The expression levels of proteins of the ERS-associated apoptosis signaling pathway were detected using Western blotting analysis. The efficacy and biosafety of SNX-2112 were also investigated in a mouse xenograft model. RESULTS: Low-intensity US combined with SNX-2112 exhibited significant antitumor effect, increased the absorption of SNX-2112 by cells even with a low dose, enhanced ROS generation and apoptosis. The combination regimen also inhibited the protein expression of Hsp90 and triggered apoptosis through endoplasmic reticulum stress (ERS) by enhancing PERK, CHOP and Bax protein levels, while downregulating the level of Bcl-2. Additionally, N-acetyl-L-cysteine (NAC), ROS scavenger, was able to reverse these results. Low-intensity US combined with SNX-2112 significantly inhibited tumor growth, prolonged survival of mice, decreased proliferation and promoted apoptosis with no visible damage or abnormalities in major organs in the mouse xenograft model with tongue squamous cell carcinoma. CONCLUSION: The antitumor effects of SNX-2112 were enhanced by low-intensity US. The most probable mechanism was that US sonoporation induced more SNX-2112 delivery to the cells and enhanced ROS production, triggering the ERS-associated apoptosis signaling pathway. Therefore, low-intensity US may increase the efficiency of conventional chemotherapy and reduce the dosage of SNX-2112 required and its side effects.

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1.

BACKGROUND/AIMS: Emerging evidence suggests that the propagation of oral squamous cell carcinoma (OSCC) is influenced by the abnormal expression of microRNAs (miRNAs). This study aimed to characterize the involvement of miR-182-5p in OSCC by targeting the calcium/ calmodulin-dependent protein kinase II inhibitor CAMK2N1. METHODS: miR-182-5p expression was quantified in OSCC tissues and cell lines with reverse transcription polymerase chain reaction (RT-PCR). Cell colony formation, Cell Counting Kit-8 (CCK-8), Ki-67, and nude mouse xenograft assays were used to characterize the role of miR-182-5p in the proliferation of OSCC. A miR-182-5p target gene was identified with western blotting, RT-PCR, and luciferase activity assays. OSCC patient survival based on CAMK2N1 expression was also analyzed. RESULTS: miR-182-5p was up-regulated in in vitro cell lines and in vivo clinical OSCC samples. CCK-8, colony formation, and Ki-67 assays revealed that miR-182-5p promoted the growth and proliferation of OSCC cells. miR-182-5p directly targeted CAMK2N1, as evidenced by luciferase assays and target prediction algorithms. CAMK2N1 operated as a tumor suppressor gene in patients with OSCC. Down-regulating miR-182-5p expression in the CAL-27 cell line restored CAMK2N1-mediated OSCC cell proliferation. miR-182-5p expression inhibited the activation of AKT, ERK1/2, and NF-κB. Mice injected with CAL-27 cells transfected with miR-182-5p-inhibitor demonstrated a significant increase in tumor size and weight and increased CAMK2N1 mRNA and protein expression compared with the miR-negative control group. CONCLUSION: The miR-182-5p-CAMK2N1 pathway can be potentially targeted to regulate the proliferation of OSCC cells.

Identification of a mutL­homolog 1 mutation via whole­exome sequencing in a Chinese family with Gardner syndrome.

Gardner syndrome (GS), a variant of familial adenomatous polyposis, is a rare genetic disorder with autosomal dominant inheritance, characterized by the presence of multiple intestinal polyps, multiple osteomas, dental abnormalities and soft tissue tumors. To date, only a few gene mutations have been demonstrated to be responsible for GS. To explore potential unknown mutations responsible for GS, the present study used whole­exome sequencing of two affected individuals from a family with GS to identify a candidate mutation in mutL­homolog (MLH)1. The two patients with GS were diagnosed based on a combination of clinical features, family history, physical examinations and cone­beam computed tomographic imaging. Through whole­genome sequencing, the present study subsequently identified a missense mutation in MLH1 (NM_000249.3:p.Tyr379Ser/c.1136A>C), which was further confirmed by Sanger sequencing. Furthermore, the amino acid residue p.Tyr379 was identified to be highly conserved among different species through sequence alignment with ClustalW2. In conclusion, the results identified for the first time a MLH1 missense mutation (NM_000249.3:​p.Tyr379Ser/c.1136A>C) in a Chinese family with GS, thus broadening the range of mutated genes associated with GS. This highlights the value of whole­exome sequencing in identifying disease mutations in a family.

Stress analysis of simulated maxillary first molar prepared with three rotary nickel-titanium instruments / 口腔疾病防治

Objective@# To compare the differences in the stress distribution in simulated first molars prepared with three rotary nickel-titanium instruments. @*Methods @#Four simulated first molars were prepared without instruments and with Reciproc, WaveOne and Protaper. Before and after preparation, each simulated molar was scanned by Micro-CT. The data were imported to Mimics 16.0 software to establish three-dimensional models. Finite element analysis was processed with Abaqus 6.14 software under conditions of longitudinal and lateral load. @*Results@# Under vertical load conditions, the maximum von Mises stress of the enamel increased by 1.36%, 21.48% and 20.99% in the Reciproc, WaveOne and Protaper groups, respectively, after preparation, while the maximum von Mises stress of the cementum increased by 55.98%, 41.18% and 33.04%, respectively, and the maximum von Mises stress of the alveolar bone increased by 45.55%, 40.37% and 24.09%, respectively. Under 45° lateral load conditions, the maximum von Mises stress of the enamel increased by 1.79%, -4.58% and 3.82% in the Reciproc, WaveOne and Protaper groups, respectively, after preparation, while the maximum von Mises stress of cementum increased by 16.33%, 7.58% and 4.32%, respectively, and the maximum von Mises stress of the alveolar bone increased by 46.82%, 36.40% and 8.29%, respectively. Under the same conditions, the von Mises stresses of the cementum and alveolar bones of the simulated molars were higher after preparation than before preparation, especially under lateral load conditions. The stress was focused on the border between the crown and the root. The von Mises stress of the cementum and alveolar bones increased much more in the Reciproc group than in the other two groups under both conditions.@*Conclusion@#The von Mises stress of simulated molars was greater after preparation than before preparation. The von Mises stress of the cementum and alveolar bones increased much more in the Reciproc group than in the other two groups.

Influencing factors of the accuracy of digital surgical implant-guide plate / 口腔疾病防治

@#With the increasing development of digital technologies, digital surgical templates have been widely used in stomatology. However, the accuracy of digital surgical templates is always a consideration for many researchers and dentists. This article analyzed the factors affecting the accuracy of digital surgical templates and found that errors arise from six factors, including the design and manufacture of the templates, implant guide support, implant systems and guide systems, implant length, bone density and the clinical experience of the operator; this literature review aims to reduce or eliminate human factors and improve accuracy, objectivity and security in implant placement.

The diagnosis and treatment progress of Gardner syndrome / 口腔疾病防治

@#Gardner syndrome is a rare disease in oral and maxillofacial diseases which is characterized by intestinal polyposis, multiple osteomas, skin and soft tissue tumors. Early treatment has a better prognosis; therefore the early diagnosis of Gardner syndrome is very important. Maxillofacial pathology always appears to precede the other pathologies, so the importance of early detection of the syndrome by dentists is also emphasized. This review summarizes the etiology of Gardner syndrome-related mutations and the clinical manifestations of Gardner syndrome characterized by oral and maxillofacial deformities, multiple gastrointestinal polyps, and desmoid tumour, and their associated treatment.

The immediate implant and immediate restoration in the anterior maxilla with the digital technique: case report and literature review / 口腔疾病防治

Objective @#To describe a novel workflow for the anterior dental esthetics in immediate implant and immediate aesthetic restoration with digital technique. @*Methods @#Before the implant placement, a intra-oral optical scan(IOS) combined with CBCT was performed to virtually design the 3D implant position and restoration. A surgical guide and an individualized Ti abutment restoration was CAD/CAM-fabricated out of the PMMA-based in a fully digital workflow and seated at the stage of minimal invasive surgery.@*Results @#The technique achieved immediate implant and immediate restoration after tooth extraction. Immediate restoration of temporary crown could be completed immediately in second patient visit after the operation, finally realized the aesthetic implantation with preserved soft tissue contour. @*Conclusin @# The fully digital technique changed the conventional workflow which achieves more efficiency and better aesthetic effect.

CCDC40 mutation as a cause of primary ciliary dyskinesia: a case report and review of literature.

BACKGROUND AND AIMS: Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder. Genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, situs inversus and, frequently, male infertility in PCD. To date, although several genes have been implicated in PCD, the genetic bases of most cases of PCD remain elusive. METHODS: By applying a whole-exome sequencing strategy, we reported a case of PCD carrying a novel mutant alleles in CCDC40 gene, and did literature review. RESULTS: A 36-year-old nonsmoking Chinese man suffered from chronic cough since childhood and an 8-year history of primary infertility. Lung biopsy showed respiratory bronchiolitis. Chest images showed bronchiectasis and situs inversus. Semen analysis showed high sperm counts and poor sperm motility. Transmission electron microscopy (TEM) of cilia cross-sections showed ultrastructural defects, including inner dynein arms (IDA) defect and axonemal disorganization. To identify gene mutations that cause PCD, we performed exome sequencing to analyze genome of this patient, and discovered a previously uncharacterized mutant alleles (NM_001243342.1:c.2609G>A; p. R870H) in CCDC40 gene. In addition, we summarize the PCD disease-causing genes and CCDC40 mutant sites based on current literature. CONCLUSIONS: We identified a novel mutant alleles in CCDC40 gene, which altered the protein sequence and resulted in the ultrastructural defects in the microtubule structure of cilia. Thereby, these defects lead to the patient with bronchiectasis, bronchiolitis and infertility.

[Clinical application of lateral lag screw in fixing intracapsular sagittal condylar fracture].

OBJECTIVE: To introduce the clinical application and curative effect of lateral lag screw technique in fixing condylar intracapsular sagittal fractures. METHODS: Thirteen condyles with intracapsular sagittal fracture of 11 cases were fixed using lateral lag screw technique. Curative effects were observed by clinical and radiological follow-up for 6 approximately 30 months (mean 12 months) postoperatively. RESULTS: The favorable results were obtained in all cases. All patients were satisfied with the clinical results. slight malocclusion existed in 2 cases. Radiological abnormalities were seen in 3 cases by CT scanning, but without any obvious function disturbances. CONCLUSIONS: Lateral lag screw technique is a simple and effective treatment in fixing intracapsular sagittal condylar fractures.