Primary intraosseous adenoid cystic carcinoma of the jaw: clinical and histopathologic analysis.

PURPOSE: Adenoid cystic carcinoma (ACC), formerly known as cylindroma, is a malignant epithelial neoplasm typically derived from the salivary glands. Of all salivary gland tumors, the incidence of malignant salivary gland tumor has been 15 to 32% in the parotid glands, 70 to 90% in the sublingual glands, and about 50% in the minor salivary glands. Intraosseous ACC of the jaw has rarely been reported and is poorly understood. The aim of the present study was to analyze this tumor clinically and histopathologically to improve the diagnosis, management, and treatment. MATERIALS AND METHODS: We collected the records of 16 patients with intraosseous ACC from 1998 to 2013, who had been treated at our hospital, including clinical data and follow-up information. We then analyzed the patients' clinical features, diagnosis, treatment, and prognosis. RESULTS: The average age of the 16 patients was 56.8 years, and the male/female ratio was 0.8. The primary manifestations of the tumor were obviously different. Tumor excision was performed and followed by radiotherapy or chemotherapy, or both. The average follow-up period was 57.2 months, and the average follow-up period for patients who were alive and tumor free was 52.3 months. The survival rate was 68.8% after treatment. All these results were generally in agreement with those from previous reports. CONCLUSIONS: The differential diagnosis of intraosseous ACC from other common tumors of jaws should be determined by the clinical, radiographic, and histopathologic subtypes. For treatment, surgery is the first choice for patients, and radiotherapy or chemotherapy might improve the prognosis in the postoperative period. In addition, the histopathologic subtypes and biologic processes of ACC are related to patient prognosis.

[Application of three dimensional model in treatment of superolateral dislocation of mandibular condyle].

OBJECTIVE: To assess the application of three-dimensional jaw model in treatment of superolateral dislocation of condyle. METHODS: Nine patients with superolateral dislocation of condyle and symphyseal fractures were admitted in hospital from June 2008 to June 2013. Spiral CT scan on maxilla and mandible was performed，and three-dimensional jaw model was constructed with rapid prototyping technology. According to conditions of condylar superolateral dislocation model，the operation scheme was designed. The symphyseal fracture line was made and fracture was reduced on three-dimensional jaw model. Individualized prefabricated reconstructive titanium plate was made on symphyseal fracture model. Symphyseal fracture was replaced with individualized prefabricated mandibular reconstruction titanium plate according to occlusal relationship. At the same time，reduction of condylar superolateral dislocation was accomplished. RESULTS: Operations were successfully completed in 9 cases under guidance of three dimensional jaw model surgery. Operative incision was primarily healed，and occlusal relationship was restored. Postoperative CT scan showed that the locations of condyle in 9 cases were completely restored. Patients were followed-up for 6-28 months with a median of 18 months. The maximum of mouth opening was 3.1- 4.2 cm with a medians of 3.3 cm，and the occlusal relationship of all patients was normal after surgery. CONCLUSION: Three-dimensional jaw model can show complete status of condylar superolateral dislocation and symphyseal fracture. The model can accurately shape symphyseal reconstructive titanium plate and restore condylar superolateral dislocation during reductive surgery.

Bone metastases in oral squamous cell carcinoma: A real-world retrospective study based on the SEER database.

BACKGROUND: Bone metastases are rare in oral squamous cell carcinoma (OSCC). It has not been defined on the risk and prognosis of OSCC patients with bone metastases. The purpose of this study was to assess the factors associated with the development and prognosis of bone metastases among OSCC patients. METHODS: Demographic and clinicopathological characteristics of OSCC patients diagnosed between 2010 and 2019 was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. To explore risk factors for developing bone metastases and prognosis, the univariate and multivariate logistic and Cox regression analysis were performed, further the predictive nomogram models were constructed. RESULTS: The incidence rate of bone metastases in newly diagnosed OSCC patients was 0.91 % (95 %CI 0.81% -1.02 %). Ultimately, 137 OSCC patients with bone metastases and 19,469 OSCC patients without bone metastases were included in the present study. Pathological grade, primary site, T/N stage and distant organ metastases (liver/lung/brain) were independently associated with the risk of developing bone metastases among OSCC patients. The C-index of a constructed risk-predicting nomogram was 0.86 (95 %CI 0.83-0.89). Multivariate Cox regression analysis indicated that lung metastases, the use of surgery as well as chemotherapy were three independent prognostic factors. The C-indexes of constructed risk-predicting nomograms were 0.70 (95 %CI 0.65-0.75), 0.68 (95 %CI 0.63-0.73) for OS and CSS, respectively. Calibration plots demonstrated an agreementbetween the established nomogram's predicted survival and actual survival. In addition, decision curve analysis (DCA) indicated these established nomograms had considerable net benefits and clinical utilities. CONCLUSION: This study defined the risk and prognostic factors for bone metastases among OSCC patients and the established nomograms were well calibrated for discrimination to predict bone metastasis development and prognosis.

A new gamboge derivative compound 2 inhibits cancer stem-like cells via suppressing EGFR tyrosine phosphorylation in head and neck squamous cell carcinoma.

Cancer stem-like cells represent a population of tumour-initiating cells that lead to the relapse and metastasis of cancer. Conventional anti-cancer therapeutic drugs are usually ineffective in eliminating the cancer stem-like cells. Therefore, new drugs or therapeutic methods effectively targeting cancer stem-like cells are in urgent need to successfully cure cancer. Gamboge is a natural anti-cancer medicine whose pharmacological effects are different from those of conventional chemotherapeutical drugs and they can kill some kinds of cancer cells selectively. In this study, we identified a new gamboge derivative, Compound 2 (C2), which presents eminent suppression effects on cancer cells. Interestingly, when compared with cisplatin (CDDP), C2 effectively suppresses the growth of both cancer stem-like cells and non-cancer stem-like cells derived from head and neck squamous cell carcinoma (HNSCC), inhibiting the formation of tumour spheres and colony in vitro, resulting in the loss of expression of multiple cancer stem cell (CSC)-related molecules in HNSCC. Treating with C2 effectively inhibited the growth of HNSCC in BALB/C nude mice. Further investigation found that C2 notably inhibits the activation of epithelial growth factor receptor and the phosphorylation of its downstream protein kinase homo sapiens v-akt murine thymoma viral oncogene homolog (AKT) in HNSCC, resulting in down-regulation of multiple CSC-related molecules in HNSCC. Our study has demonstrated that C2 effectively inhibits the stem-like property of cancer stem-like cells in HNSCC and may be a hopeful targeting drug in cancer therapy.

20(S)-Protopanaxadiol (PPD) analogues chemosensitize multidrug-resistant cancer cells to clinical anticancer drugs.

Novel 20(S)-protopanoxadiol (PPD) analogues were designed, synthesized, and evaluated for the chemosensitizing activity against a multidrug resistant (MDR) cell line (KBvcr) overexpressing P-glycoprotein (P-gp). Structure-activity relationship analysis showed that aromatic substituted aliphatic amine at the 24-positions (groups V) effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as docetaxel (DOC), vincristine (VCR), and adriamycin (ADM). PPD derivatives 12 and 18 showed 1.3-2.6 times more effective reversal ability than verapamil (VER) for DOC and VCR. Importantly, no cytotoxicity was observed by the active PPD analogues (5µM) against both non-MDR and MDR cells, suggesting that PPD analogues serve as novel lead compounds toward a potent and safe resistance modulator. Moreover, a preliminary mechanism study demonstrated that the chemosensitizing activity of PPD analogues results from inhibition of P-glycoprotein (P-gp) overexpressed in MDR cancer cells.

Malignant Myoepithelioma of the Head and Neck: Demographics, Clinicopathological Characteristics, Treatment, and Prognosis.

Malignant myoepithelioma of the head and neck (HNMM) is a rare malignancy, and its characteristics and survival rates have not been well-defined. This study aimed to define the epidemiology of HNMM and identify the prognostic factors associated with the disease. Data on all patients diagnosed with HNMM between 1991 and 2016 were gathered from the Surveillance Epidemiology and End Results (SEER) database. The demographics, clinicopathological characteristics, treatment, and prognoses of the patients were described. Cox regression analysis was used to identify the prognostic factors, and the prognostic nomograms for overall survival (OS) and disease-specific survival (DSS) were constructed. A total of 333 cases of HNMM were identified. The average age at diagnosis was 60.6 years, and 50.1% of the patients were men. After diagnosis, 46.2% of patients underwent surgery alone, 43.5% of patients underwent surgery and radiotherapy, and 3.6% of patients received only radiotherapy. Survival analysis showed that the 5-year OS and DSS for all HNMM patients were 69.7 and 82.1%, respectively. In the multivariate analysis model, the undifferentiated pathological grade (P <0.05) and M1 in the M category (P <0.01) were independent prognostic factors for poor OS and DSS, whereas the use of surgical resection was an independent favorable prognostic factor for both OS and DSS (P <0.05). The prognostic nomograms for OS and DSS prediction were constructed; the C-index values for OS and DSS prediction were 0.78 (95% CI 0.70-0.86) and 0.79 (95% CI 0.67-0.90), respectively. In conclusion, this SEER data-based study demonstrated that HNMM patients often had a favorable prognosis, and distant metastasis, pathological grade, and the use of surgery contributed to their survival. Furthermore, we developed a prognostic nomogram to predict OS and DSS for HNMM patients to aid physicians in the clinical management of this rare disease.

Clinicopathological characteristics and prognostic analysis of lymphoepithelial carcinoma of salivary gland: a population-based study.

BACKGROUND: The purpose of this study was to elucidate the clinicopathological characteristics of patients with lymphoepithelial carcinoma of salivary gland (LEC-SG) and determine the factors associated with survival. METHODS: A total of 179 LEC-SG patients from the Surveillance, Epidemiology, and End Results (SEER) database between 1975 to 2016 were included. The clinicopathological characteristics and overall survival of LEC-SG patients were described, and the features affecting prognosis were further determined using Kaplan-Meier Curves and Cox survival analysis. RESULTS: The median overall survival of LEC-SG patients was 206 months, and the 1-, 5-, 10- and 20-year survival rates were 91.0%, 80.2%, 66.4%, and 37.6%, respectively. The prognoses were significantly associated with age, ethnicity, marital status, tumor invasion, as well as lymph node metastases [P<0.01 for all). Surgical resection could significantly improve the prognosis of this disease (median overall survival (mOS): 219 vs. 68 months, P<0.01]. Postoperative radiotherapy could improve long-term survival and decrease the risk of death among patients who survive exceed 10-year after surgery. The Cox regression analysis showed that old age (>60 years) and lymph node metastases were independently associated with poor survival (P<0.05 for both). Conversely, the use of surgery was an independent favorable prognostic factor [hazard ratio (HR) 0.29, 95% CI: 0.13-0.66]. CONCLUSIONS: LEC-SG patients had a favorable prognosis with a mOS of 206 months. Old age, lymph node metastases, the use of surgery were independently associated with survival of LEC-SG patients.

Gambogic acid as a non-competitive inhibitor of ATP-binding cassette transporter B1 reverses the multidrug resistance of human epithelial cancers by promoting ATP-binding cassette transporter B1 protein degradation.

Gambogic acid (GA) is known for its anti-cancer activity in a phase II clinical trial. However, the detailed molecular mechanisms of its anti-multidrug resistance remain unclear. The present study was designed to study the relationship between GA and multidrug-resistant protein ATP-binding cassette transporter B1 (ABCB1). GA dose dependently inhibited ABCB1 activity levels in the in vitro Pgp-Glo assay system and increased the cellular accumulation of ABCB1 substrate adriamycin. Although GA had no significant influence on ABCB1 mRNA in the real-time PCR assay, Western blot detection indicated the compound reduced ABCB1 protein levels. Further study showed the proteasome inhibitor MG-132 reversed the GA-decreased ABCB1 level and prolonged half-life of ABCB1. It was also found that GA coordinated with other anti-cancer drugs (such as adriamycin, docetaxel, verapamil and protopanaxadiol) to enhance cellular cytotoxicity on human epithelial cancer cell lines with higher ABCB1 expression levels. These data suggest that GA functions as a non-competitive inhibitor of ABCB1 by directly inhibiting and reducing its expression levels by promoting protein degradation through post-translational proteasome pathway. The results of this study will aid in the understanding of the synergistic effects of combining GA with other drugs as a new anti-multidrug-resistant agent.