3D-printed bredigite scaffolds with ordered arrangement structures promote bone regeneration by inducing macrophage polarization in onlay grafts.

Bone tissue engineering scaffolds may provide a potential strategy for onlay bone grafts for oral implants. For determining the fate of scaffold biomaterials and osteogenesis effects, the host immune response is crucial. In the present study, bredigite (BRT) bioceramic scaffolds with an ordered arrangement structure (BRT-O) and a random morphology (BRT-R) were fabricated. The physicochemical properties of scaffolds were first characterized by scanning electron microscopy, mechanical test and micro-Fourier transform infrared spectroscopy. In addition, their osteogenic and immunomodulatory properties in an onlay grafting model were investigated. In vitro, the BRT-O scaffolds facilitated the macrophage polarization towards a pro-regenerative M2 phenotype, which subsequently facilitated the migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. In vivo, an onlay grafting model was successfully established in the cranium of rabbits. In addition, the BRT-O scaffolds grafted on rabbit cranium promoted bone regeneration and CD68 + CD206 + M2 macrophage polarization. In conclusion, the 3D-printed BRT-O scaffold presents as a promising scaffold biomaterial for onlay grafts by regulating the local immune microenvironment.

Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration.

Biomaterials can modulate the local immune microenvironments to promote peripheral nerve regeneration. Inspired by the spatial orderly distribution and endogenous electric field of nerve fibers, we aimed to investigate the synergistic effects of electrical and topological cues on immune microenvironments of peripheral nerve regeneration. Nerve guidance conduits (NGCs) with aligned electrospun nanofibers were fabricated using a polyurethane copolymer containing a conductive aniline trimer and degradable L-lysine (PUAT). In vitro experiments showed that the aligned PUAT (A-PUAT) membranes promoted the recruitment of macrophages and induced their polarization towards the pro-healing M2 phenotype, which subsequently facilitated the migration and myelination of Schwann cells. Furthermore, NGCs fabricated from A-PUAT increased the proportion of pro-healing macrophages and improved peripheral nerve regeneration in a rat model of sciatic nerve injury. In conclusion, this study demonstrated the potential application of NGCs in peripheral nerve regeneration from an immunomodulatory perspective and revealed A-PUAT as a clinically-actionable strategy for peripheral nerve injury.

Developing and Validating an Intelligent Mouth-Opening Training Device: A New Solution for Restricted Mouth Opening.

Restricted mouth opening (trismus) is one of the most common complications following head and neck cancer treatment. Early initiation of mouth-opening exercises is crucial for preventing or minimizing trismus. Current methods for these exercises predominantly involve finger exercises and traditional mouth-opening training devices. Our research group successfully designed an intelligent mouth-opening training device (IMOTD) that addresses the limitations of traditional home training methods, including the inability to quantify mouth-opening exercises, a lack of guided training resulting in temporomandibular joint injuries, and poor training continuity leading to poor training effect. For this device, an interactive remote guidance mode is introduced to address these concerns. The device was designed with a focus on the safety and effectiveness of medical devices. The accuracy of the training data was verified through piezoelectric sensor calibration. Through mechanical analysis, the stress points of the structure were identified, and finite element analysis of the connecting rod and the occlusal plate connection structure was conducted to ensure the safety of the device. The findings support the effectiveness of the intelligent device in rehabilitation through preclinical experiments when compared with conventional mouth-opening training methods. This intelligent device facilitates the quantification and visualization of mouth-opening training indicators, ensuring both the comfort and safety of the training process. Additionally, it enables remote supervision and guidance for patient training, thereby enhancing patient compliance and ultimately ensuring the effectiveness of mouth-opening exercises.

Precision compensation method for visual measurement based on nonuniform refractive index field reconstruction.

Visual measurement is widely used in industrial manufacturing and assembly fields. Due to the fact that the refractive index field of the measurement environment is inhomogeneous, the transmitted light for visual measurements will produce errors. To compensate for these errors, we introduce a binocular camera for visual measurement based on the reconstruction of a nonuniform refractive index field using the schlieren method, followed by the reduction of the inverse ray path by the Runge-Kutta method to compensate for the measurement error introduced by the nonuniform refractive index field. Finally, the effectiveness of the method is experimentally verified, with a reduction in measurement error of about 60% in the built measurement environment.

Curcumin nanoemulsions inhibit oral squamous cell carcinoma cell proliferation by PI3K/Akt/mTOR suppression and miR-199a upregulation: A preliminary study.

BACKGROUND: Accumulating evidence indicates that curcumin (CUR) has anticancer properties in various cancers including oral squamous cell carcinoma (OSCC), but CUR is greatly restricted in clinical studies and applications due to its low bioavailability. Interestingly, the bioavailability of CUR was found to be significantly improved using loaded lipid nanoemulsions (NEs). OBJECTIVES: To investigate the effect of CUR-NEs on cell proliferation of OSCC HSC-3 cells in vitro, and explore the potential mechanism of this effect in a preliminary study. RESULTS: CUR-NEs exhibited significantly cytotoxic effects on OSCC cells in a dose-dependent manner, compared with the control. The percentage of cells in proliferative phases (S + G2/M) was gradually decreased in a dose- or time-dependent manner caused by CUR-NEs. Moreover, CUR-NEs downregulated the protein expression of PI3K/Akt/mTOR and upregulated the expression of miR-199a that targeted PI3K in a dose- or time-dependent manner in OSCC cells. Importantly, CUR-NEs cloud effectively counteract the influence on cell proliferation of OSCC cells and the proliferative phases of cell cycle caused by miR-199a inhibitor a time-dependent manner. CONCLUSIONS: This in vitro preliminary study indicated that CUR-NEs may be an effective therapeutic agent for OSCC. Such effects could be related to inhibition of OSCC cell proliferation by PI3K/Akt/mTOR suppression and miR-199a upregulation.

Prognostic factors and treatment considerations of submandibular gland carcinomas: A population-based study.

OBJECTIVES: The therapeutic regimen of submandibular gland carcinoma (SGC) has not reached consensus, especially for the neck treatment of patients with cN0. MATERIALS AND METHODS: Patients with SGC were identified from the medical database of Shanghai Ninth People's Hospital. Kaplan-Meier analysis, univariate and multivariate Cox regression were employed to evaluate the survival and independent prognostic factors. RESULTS: Two hundred and fifteen patients with SGC were retrospectively reviewed. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 71.5% and 77.8%, respectively. Multivariate analysis revealed that histological grade, cT classification, cN classification, and perineural invasion (PNI) were independent prognostic factors for DFS, while histological grade, cT classification, cN classification, and age were those for OS. The neck dissection showed no significant survival benefit for patients with cN0. Lung was the most common site of distant metastasis (16.7%). CONCLUSIONS: Histological grade, cT classification, cN classification, age, and PNI were independent prognostic factors of patient with SGC, which should be the main considerations for making therapeutic regimens. Our study also verifies the neck dissection of patient with cN0 is unnecessary, and postoperative radiotherapy (PORT) is vital for patients with pN+.

Carcinoma ex pleomorphic adenoma of the submandibular gland: A retrospective analysis of 86 patients.

OBJECTIVES: To evaluate the prognostic and locoregional metastatic features of carcinoma ex pleomorphic adenoma of submandibular gland (SMG-CXPA) and improve the understanding of this uncommon condition. PATIENTS AND METHODS: We retrospectively reviewed patients who were diagnosed with SMG-CXPA. The survival data of SMG-CXPA patients were statistically analyzed using Cox regression and Kaplan-Meier method. The associations between cervical metastasis and clinicopathological parameters were evaluated using chi-squared test. Additionally, two different histological categories (histological grade and invasiveness) and their combination were evaluated with the Kaplan-Meier method and receiver operating characteristic curves. RESULTS: In total, 86 patients were diagnosed: 38 clinically node-negative, 31 pathologically node-negative, and 17 node-positive patients. Clinical tumor stage and histological grade were two independent prognostic factors for SMG-CXPA. There were significant correlations between sex, tumor size, clinical tumor stage, clinical lymph node stage, histological grade, invasiveness, malignant components, perineural invasion, and no specific criteria exist for the clinical outcome. CONCLUSION: SMG-CXPA is a high-grade malignancy with an unfavorable prognosis. Elective neck dissection should be performed in SMG-CXPA patients with a risk of locoregional metastasis. Histological grade seems to be a more valuable predictor of lymph node involvement than invasiveness.

Adenoid cystic carcinoma of submandibular gland: Emphasis on locoregional metastasis and prognosis.

OBJECTIVES: To analyze the clinicopathological features, locoregional or distant metastasis, and prognosis of adenoid cystic carcinoma of submandibular gland (SMG-AdCC). METHODS: The clinicopathological data of 80 patients with SMG-AdCC from January 2005 to December 2017 were analyzed retrospectively, and the relationships between different parameters of SMG-AdCC and its locoregional or distant metastasis or prognosis were analyzed. RESULTS: As of December 2019, 41 patients (51.25%) were tumor-free, while 20 patients were found to be living with tumors. The locoregional metastasis rate of grade II-III SMG-AdCC were found to be significantly higher than that of grade I. The five-year DFS and OS rates were 70.8% and 87.1%, respectively. Univariate analysis showed that clinical size, extraglandular extension, pathological grade, pathological node (pN) status, and perineural invasion were correlated with DFS. Multivariate Cox regression analysis showed that pathological grade and extraglandular extension were independent prognostic factors for DFS; pN status and extraglandular extension were independent prognostic factors impacting OS. CONCLUSION: The pathological grade is a risk factor for locoregional metastasis of SMG-AdCC. Pathological grade, pN status, and status of extraglandular extension are independent prognostic factors for DFS/OS in SMG-AdCC patients.

Effect of Concentrated Growth Factor on Distraction Osteogenesis of Dental Implant Distractors.

PURPOSE: The periosteum of bone segments can be destroyed during the installation of a dental implant distractor (DID) device, resulting in bone defects on the exposed side of the distraction gap. The purpose of this animal experiment is to explore the application of concentrated growth factor (CGF) in DID surgery, which can induce angiogenesis and osteogenesis and improve osteogenesis defects caused by periosteum loss on the exposed side of bone segments. METHODS: CGF is the latest generation of platelet concentrate. Twenty-four DID devices inserted into the tibias of 8 goats were evenly divided into the CGF and control groups. Following 10 days of distraction and a 12-week consolidation period, all 8 animals were euthanized to retrieve their tibias. The distraction gap between each segment was measured at 5 points, and the average value was taken as the computed tomography (CT) value of the distraction gap at 4, 8, and 12 weeks after distraction. The vascular density and trabecular bone volume of each DID distraction gap were determined and statistically compared between the 2 groups. RESULTS: The CT value of the distraction gap increased gradually in control groups at 4, 8, and 12 weeks after distraction to 319.3 ± 14.6, 449.3 ± 34.4, and 614.0 ± 15.6 HU in the control group and 368.3 ± 8.8, 544.5 ± 12.3, and 661.0 ± 8.1 HU in the CGF group. The trabecular bone volume was 281.7 ± 16.5 and 209.7 ± 21.6 µm2 in the CGF group and control group. The vascular density was 17.7 ± 2.1 and 11.7 ± 1.9 in the CGF group and control group. Statistically significant differences were observed in the CT value (P = .002), vascular density (P = .023), and trabecular bone volume (P = .010) between the CGF and control groups. CONCLUSIONS: The application of an autogenous CGF membrane in DID surgery repaired bone defects caused by osteolysis around osteotomy segments.

Analysis of related factors of long-term complications after vascularized fibular transplantation.

OBJECTIVES: Free fibula flap is the first choice for jaw reconstruction in head and neck oncology, but postoperative complications in donor site are ignored always. The main purpose of this study was to investigate the long-term complications and potential risk factors of donor site after vascularized fibular transplantation, and to explore the precautions of preparing vascularized fibular flap and the measures of preventing donor site complications. MATERIALS AND METHODS: Data were retrospectively collected on 31 patients who had undergone immediate mandibular reconstruction with a fibular flap after segmental mandibulectomy from 2013 to 2018 in Shanghai Ninth People's Hospital. Thirty-one patients (24 male, 7 female) were available for the long-term complications in donor site analysis from 25 to 96 months after surgery. The data were collected and analyzed, including age at time of operation, early postoperative complications, incidence of dorsiflexion weakness of hallux, donor site missing fibula length, proximal and distal stump fibula length, and subjective evaluation of foot function (AOFAS-hallux, AOFAS-ankle hindfoot, Enneking lower limb function score). In the single-factor analysis in this study, the correlation between related factors and long-term complications was statistically analyzed. For inter-group comparisons of quantitative data, if the normal distribution was satisfied, two independent sample t-tests were used; p < 0.05 was statistical significant. If the normal distribution was not satisfied, Wilcoxon rank-sum test was used, and p < 0.05 was considered statistically significant. For qualitative data, the Fisher exact probability method was compared between group differences, and p < 0.05 was statistically significant. RESULTS: The most commonly encountered complication in our series was dorsiflexion disorder, flexion deformity, numbness of the lateral side of the lower leg, and dorsum of the foot. Ten patients (32.26%) developed hallux flexion deformity after operation, 17 patients (54.84%) had hallux dorsiflexion dysfunction after operation, and 10 patients (32.26%) had numbness of the lateral side of the lower leg and dorsum of the foot. The incidence of hallux dorsiflexion dysfunction, thumb flexion deformity, and sensory disturbance was higher than that of other long-term complications in the donor area. The residual length of fibular distal was related to the dorsiflexion dysfunction and flexion deformity of hallux (p < 0.05). The early complications of donor site were correlated with the hallux dorsiflexion dysfunction (p < 0.05). CONCLUSIONS: The incidence of dorsiflexion disorder and flexion deformity is higher in patients after fibula transplantation. The less the residual length of fibular distal, the more obvious the long-term complications in the donor site, and the higher the incidence of dorsiflexion dysfunction and flexion deformity of hallux. CLINICAL RELEVANCE: The long-term complications of donor site after fibular transplantation seriously affect the quality of life of patients and provide clinical reference for further reducing the occurrence of donor site complications.

Exosome-derived long non-coding RNA ADAMTS9-AS2 suppresses progression of oral submucous fibrosis via AKT signalling pathway.

Oral submucosal fibrosis (OSF) is one of the pre-cancerous lesions of oral squamous cell carcinoma (OSCC). Its malignant rate is increasing, but the mechanism of malignancy is not clear. We previously have elucidated the long non-coding RNA (lncRNA) expression profile during OSF progression at the genome-wide level. However, the role of lncRNA ADAMTS9-AS2 in OSF progression via extracellular communication remains unclear. lncRNA ADAMTS9-AS2 is down-regulated in OSCC tissues compared with OSF and normal mucous tissues. Low ADAMTS9-AS2 expression is associated with poor overall survival. ADAMTS9-AS2 is frequently methylated in OSCC tissues, but not in normal oral mucous and OSF tissues, suggesting tumour-specific methylation. Functional studies reveal that exosomal ADAMTS9-AS2 suppresses OSCC cell growth, migration and invasion in vitro. Mechanistically, exosomal ADAMTS9-AS2 inhibits AKT signalling pathway and regulates epithelial-mesenchymal transition markers. Through profiling miRNA expression profile regulated by exosomal ADAMTS9-AS2, significantly enriched pathways include metabolic pathway, PI3K-Akt signalling pathway and pathways in cancer, indicating that exosomal ADAMTS9-AS2 exerts its functions through interacting with miRNAs during OSF progression. Thus, our findings highlight the crucial role of ADAMTS9-AS2 in the cell microenvironment during OSF carcinogenesis, which is expected to become a marker for early diagnosis of OSCC.

A covalently bound inhibitor triggers EZH2 degradation through CHIP-mediated ubiquitination.

Enhancer of zeste homolog 2 (EZH2) has been characterized as a critical oncogene and a promising drug target in human malignant tumors. The current EZH2 inhibitors strongly suppress the enhanced enzymatic function of mutant EZH2 in some lymphomas. However, the recent identification of a PRC2- and methyltransferase-independent role of EZH2 indicates that a complete suppression of all oncogenic functions of EZH2 is needed. Here, we report a unique EZH2-targeting strategy by identifying a gambogenic acid (GNA) derivative as a novel agent that specifically and covalently bound to Cys668 within the EZH2-SET domain, triggering EZH2 degradation through COOH terminus of Hsp70-interacting protein (CHIP)-mediated ubiquitination. This class of inhibitors significantly suppressed H3K27Me3 and effectively reactivated polycomb repressor complex 2 (PRC2)-silenced tumor suppressor genes. Moreover, the novel inhibitors significantly suppressed tumor growth in an EZH2-dependent manner, and tumors bearing a non-GNA-interacting C668S-EZH2 mutation exhibited resistance to the inhibitors. Together, our results identify the inhibition of the signaling pathway that governs GNA-mediated destruction of EZH2 as a promising anti-cancer strategy.

Tracking the dropout patients of neoadjuvant chemotherapy with locally advanced oral cavity cancer.

BACKGROUND: Patients with locally advanced oral cavity cancer sometimes stopped treatment after neoadjuvant chemotherapy. There are no guidelines of the management for these patients. Before designing clinical trials, we conducted this study to investigate their characteristics, reasons of dropout, and the follow-up information. METHODS: Medical records were consecutively reviewed of patients with locally advanced oral cavity cancer who underwent neoadjuvant chemotherapy from Jan 2017 to Dec 2019.Variables were compared between patients stopped treating after chemotherapy and completed treatments by student t-test and Chi-square test. Logistic regression model was used to calculate the odd rations of potential predictors of dropout. The dropout patients were followed up for reasons and results of their decision. RESULTS: A total of 171 patients were included with 23 not undergoing surgery after chemotherapy. The odd ratios of age over 65 and single marital status were 3.11 (95%CI: 1.1, 8.7) and 4.935 (95%CI: 1.5, 16.1), respectively, for the dropout. The median survival of patients without surgery was 7.4 months. Believing that chemotherapy would be effective and being afraid of the consequence of surgery were the main reasons of refusing surgery. CONCLUSIONS: The prognosis was poor of these dropout patients. Symptom relief and fear of surgery were the reasons of dropout. Age and marital status affected their decision. Clinical trials are needed to be designed for these patients.

Assessing the magnetic resonance imaging in determining the depth of invasion of tongue cancer.

OBJECTIVES: To assess the magnetic resonance imaging (MRI) in predicting tumour's depth of invasion (DOI) of tongue cancer by comparing to pathology and to determine the cut-off value of MRI-derived DOI for lymph node metastasis. PATIENTS AND METHODS: In a retrospective analysis, 156 patients with newly diagnosed tongue cancer were included. Tumour's DOI was compared between MRI measurement and pathology by Pearson correlation coefficient and paired t test. The accuracy of MRI-derived DOI was compared to the pathological DOI. The relationship between MRI-derived DOI and cervical lymph node metastasis was calculated by receiver operating characteristic curve. RESULTS: Tumour's DOI was well correlated between MRI measurement and pathology with correlation coefficients of 0.77. MRI-derived DOI was 3.4 mm (28%) larger than pathology. The accuracy of MRI in deciding pathological DOI was 67.9%. The cut-off value of MRI-derived DOI was 10.5 mm for lymph node metastasis of tongue cancer. CONCLUSION: Magnetic resonance imaging can be used as a reference to determine tumour's DOI of tongue cancer. Tumour with MRI-derived DOI larger than 10.5 mm deserves simultaneous neck dissection at initial surgery.

Salvage Surgery for Recurrent Tongue Cancer With Contralateral Neck Metastasis.

PURPOSE: Treatment recommendations have been widely reported for primary tongue squamous cell carcinoma (TSCC) with contralateral neck metastases (CNMs), but little is known concerning recurrent TSCCs with CNMs, especially in patients who have undergone ipsilateral neck dissection. The aim of this study was to estimate overall survival (OS) and to identify prognostic factors associated with OS in patients treated for recurrent TSCCs. PATIENTS AND METHODS: We performed a retrospective cohort study of patients who underwent salvage surgery (SS) for recurrent TSCC in our institution between January 2010 and December 2014. Before SS, all patients had been surgically treated for primary TSCC with ipsilateral neck dissection. The primary outcome variable was OS, and the patients were grouped by the primary predictor variable of CNM status for comparison. Other heterogeneous variables of interest included demographics, medical histories, clinicopathologic characteristics, surgical data, and adjuvant treatment modalities. In addition, the midline involvement and anatomic subsites of local recurrences were evaluated. Univariate log-rank and Cox regression tests were used for statistical analyses. RESULTS: The study sample included 177 subjects with a mean age of 55.4 years, and 44.6% were males. The median OS was 18 months. Within the entire cohort, the incidence of CNM was 23.7% (n = 42), with an inclination (n = 30) for contralateral level I or II. Factors associated with improved survival included CNM (hazard ratio [HR], 2.108; 95% confidence interval [95% CI], 1.341 to 3.315; P = .001), disease-free interval (HR, 0.601; 95% CI, 0.387 to 0.934; P = .023), and local recurrence subsite score (HR, 3.276; 95% CI, 0.924 to 11.623; P = .001). CONCLUSIONS: Patients with both recurrent TSCCs and CNMs had a dismal prognosis (OS rate, 16.2%) compared with those without CNMs (OS rate, 52.7%). SS for TSCC patients with collateral failures should be used cautiously because of the very unfavorable outcomes.

A Novel Laryngoscope-assisted Method for Sealing Pharyngocutaneous Fistula.

ABSTRACT: Pharyngocutaneous fistula (PCF) is one of the most common but stranded complications for salvage laryngectomy. As for localized fistula, there is no convincing standard and method to cure. This paper described a patient who was submitted to extensive resection of mass in right lingual root, total laryngectomy, and pharyngoesophageal reconstruction with an anterolateral thigh flap (ALTF), because of recurred carcinoma of right lingual root which invaded bilateral epiglottis. 2 weeks after surgery, subsequent pharyngocutaneous fistula developed at the junction of the tracheostomy, and maintained over 2 months under conservative treatment. With the assistance of laryngoscope, inner and outer orificiums of fistula were found and sealed by bundled iodoform strip. 9 days after sealing, fistula had been already filled with fresh granulation tissue. During 2 years after surgery, the fistula area dose not recur. This technique provides a safe and effective way for sealing the inner and outer orificiums of fistula.

High-risk lymph node ratio predicts worse prognosis in patients with locally advanced oral cancer.

BACKGROUND: To investigate the prognostic value of lymph node ratio (LNR), as well as the correlation with docetaxel, cisplatin, and 5-FU (TPF) induction chemotherapy, in patients with locally advanced oral squamous cell carcinoma (OSCC). METHODS: Two-hundred and forty-five patients from a phase 3 trial involving TPF induction chemotherapy in stage III/IVA OSCC patients (NCT01542931) were enrolled in this study between 2008 and 2010. The clinical and pathological data were collected and analyzed. The cutoff value for LNR was calculated on the receiver operating characteristic (ROC) curve. Univariate and multivariate Cox regression models, and Kaplan-Meier method were used for survival analysis. RESULTS: According to the ROC curve, the cutoff value for LNR was 7.6%. With a median follow-up period of 80 months, the OSCC patients with high-risk LNR (> 7.6%), or positive extranodal extension (ENE) had significantly worse clinical outcomes than patients with low-risk LNR (≤7.6%) or negative ENE. Multivariate analysis on pathological covariates showed that only high-risk LNR was an independent negative predictive factor for survival (P < .05). The cutoff value of LNR of 7.6% was also verified with the similar results using an open TCGA database, high-risk LNR indicating worse overall survival (P < .001) and disease-free survival (P < .001). CONCLUSION: Oral squamous cell carcinoma patients with high-risk LNR have a worse clinical outcome than patients with low-risk LNR. High-risk LNR is an independent negative predictive factor for clinical outcome in patients with locally advanced OSCC.

Role of CD44 in tumor-initiating cells of salivary gland pleomorphic adenoma: More than a surface biomarker.

CD44, a cell-surface glycoprotein, functions as a receptor for hyaluronic acid. Our research group has previously shown that CD44 is a biomarker for the CD44hi cells (tumor-initiating cells; TICs) in murine salivary gland tumors. However, little is known concerning the biological roles of CD44 in the tumorigenesis of pleomorphic adenoma. The present study is aimed to investigate the effects of CD44 on the proliferation, invasive capability, and apoptosis of TICs in vitro, as well as the tumorigenicity of TICs in vivo. The results demonstrated that knockdown of CD44 attenuated the malignant phenotype of TICs. Furthermore, in vivo xenograft studies indicated that CD44 knockdown inhibited tumorigenesis of pleomorphic adenoma. In addition, neither the CD44low cells nor the CD44-modified CD44low cells developed neo-tumors, which indicated that overexpression of CD44 did not enable the CD44low cells to be transformed into TICs. Taken together, these data demonstrate that CD44 not only acts as a biomarker, but also functions as a key player in the tumor-initiating capacity of TICs. These results shed light on the pathogenesis of salivary gland tumors and provide a potential therapeutic target for treating pleomorphic adenoma.

Transcription factor early growth response-1 plays an oncogenic role in salivary gland pleomorphic adenoma.

OBJECTIVES: Although abnormal expression of early growth response-1 (Egr1) has been revealed in various human solid tumors, the functions and potential mechanisms of Egr1 in the progression of salivary gland pleomorphic adenoma (SGPA) are not entirely understood. RESULTS: An elevated expression of Egr1 was observed both in the human salivary gland pleomorphic adenoma tissues and tumor-initiating cell (TIC) cells, when compared with control group. By loss-of-function assay, the proliferation and invasion capacities of TICs were inhibited, while the cell apoptosis was promoted, which were further evidenced by the protein expression analysis of several key apoptosis-related regulators. Furthermore, TICs with Mithramycin A (an Egr1 inhibitor) treatment achieved the same effects of endogenous Egr1 knockdown. CONCLUSIONS: All these data collectively suggest that Egr1 act as an oncogenic factor in salivary gland pleomorphic adenoma, which may be a potential target for the treatment of SGPA.

Profiling risk factors of micro-invasive carcinoma within oral potentially malignant disorders: a cross-sectional study.

OBJECTIVES: To investigate the clinicopathological profile and risk factors of micro-invasive carcinoma within oral potentially malignant disorders (OPMD). METHODS: Micro-invasive carcinomas were identified in a large prospective series of OPMD patients (n = 810) from eastern China. Logistic regression was applied to evaluate odds ratios (OR) with 95% confidence interval (CI) for indicative of malignant risk in general OPMD. RESULTS: Leukoplakia (41.4%), lichen planus (28.0%), and lichenoid lesion (23.7%) were the most 3 clinical subtypes of OPMD. A total of 62 (7.7%) micro-invasive carcinomas within OPMD were identified, and 96.8% of micro-invasive carcinoma was found within leukoplakia and erythroplakia. Multivariate regression analysis revealed that the risk of malignant change within OPMD located on lateral/ventral tongue (OR, 15.1; 95% CI, 1.85-122.8; P = 0.011) was higher than other sites. The risk of malignant change within non-homogenous type (OR, 103.3; 95% CI, 13.39-796.7; P < 0.001) was strikingly higher than other subtypes of OPMD, respectively. Intriguingly, the risk of micro-invasive carcinoma diagnosed in current smoker (OR, 3.96; 95% CI, 1.31-12.02; P = 0.015) was higher than non-smoker. CONCLUSION: This large-scale cross-sectional study elucidated the clinical factors and risk assessment of micro-invasive carcinoma within OPMD. CLINICAL RELEVANCE: Non-homogenous lesions located on lateral/ventral tongue might be monitored at closer intervals, and the need for rigorous management to detect malignant changes.