Clinical evaluation of fenestration decompression combined with secondary curettage for ameloblastoma of the jaw: retrospective radiographic analysis.

BACKGROUND: Ameloblastoma is a benign odontogenic epithelial tumor with local infiltration and a high recurrence rate that occurs most frequently in the jawbone. The aim of this study was to investigate the outcomes of fenestration decompression combined with secondary curettage (FDSC) in the surgical treatment of jaw ameloblastoma, and clarify the possibility of FDSC to become an appropriate therapeutic method for ameloblastoma with large lesion. METHODS: A retrospective analysis was carried out in 145 patients diagnosed with multicystic ameloblastoma (MA) and 88 patients with unicystic ameloblastoma (UA). These patients were divided into two groups based on the therapeutic regimen: the FDSC group and the local curettage (LC) group. Panoramic radiography was taken 2 years after curettage to evaluate the change in lesion area in each case, and the therapeutic effects of different treatment methods were further assessed by the chi square test. RESULTS: For MA, the effective rate of cystic cavity area reduction in the FDSC group (71.19%) was higher than that in the LC group (30.23%) (P < 0.001). For UA patients, the effective rate of lesion area reduction after FDSC was 93.02%, which was higher than that after LC (53.33%) (P < 0.001). Moreover, the recurrence rate of the FDSC group in the MA was 30.51%, which was significantly different from that of the LC group (P < 0.001). Regarding UA, the recurrence rates were 13.95% and 28.89%, after FDSC and LC, respectively, with no significant differences between the two groups (P > 0.05). CONCLUSIONS: FDSC exhibits a much better curative effect than LC in both MA and UA, whereas the recurrence rate of these two therapeutic strategies did not significantly differ in UA. The above data demonstrated that FDSC may serve as a routine, safe, effective and appropriate surgical treatment plan for MA or UA patients with large lesions.

Zoledronate inhibits the differentiation potential of adipose-derived stem cells into osteoblasts in repairing jaw necrosis.

OBJECTIVE: To explore the inhibitory effects of zoledronate (ZOL) on adipose-derived stem cells (ADSCs) into osteoblasts for repairing jaw necrosis. METHODS: ADSCs were induced to differentiate into osteoblasts. The differentiation characteristics of osteoblasts was observed under inverted microscope by alizarin red staining. The transwell assay was performed to evaluate the migration of ADSCs co-cultured with osteoblasts and divided into ZOL group treated with ZOL and N-ZOL group without ZOL treatment. The differentiation and proliferation characteristics of ADSCs differentiated osteoblasts were observed respectively. The expression of CTSK (Cathepsin K) and FGFR3 (Fibroblast growth factor receptor 3) in osteoblasts were analyzed by immunofluorescence and western blot. RESULTS: The differentiation degree and proliferation of ADSCs to osteoblasts in N-ZOL group were both higher than those in ZOL group. The migratory cell number in ADSCs differentiation in ZOL group was higher than that of N-ZOL group. The protein expression of CTSK and FGFR3 in ADSCs differentiated to osteoblasts in ZOL group was higher than that in N-ZOL group. CONCLUSION: The differentiation of ADSCs into osteoblasts is significantly inhibited by ZOL. Due to this reason, it may be difficult to achieve good results by ZOL induced ADSCs into osteoblasts in repairing jaw necrosis.

CD147 promotes progression of head and neck squamous cell carcinoma via NF-kappa B signaling.

CD147/basigin (BSG) is highly upregulated in many types of cancer, our previous study has found that CD147/BSG is highly expressed in head and neck squamous cell carcinoma (HNSCC) stem cells, but its role in HNSCC and the underlying mechanism is still unknown. In this study, we investigated the role of CD147 in the progression of HNSCC. Real-time PCR, western blot and immunohistochemistry were used to detect the expression of CD147 in total 189 HNSCC tissues in compared with normal tissues. In addition, we used proliferation, colony formation, cell cycle and apoptosis, migration and invasion as well as wound-healing assay to determine the biological roles of CD147 in HNSCC. Then, a xenograft model was performed to evaluate tumor-promoting and metastasis-promoting role of CD147 in HNSCC. The results showed that upregulated CD147 expression was associated with aggressive clinicopathologic features in HNSCC. In addition, CD147 promoted proliferation, migration and reduced the apoptosis phenotype of HNSCC cells in vitro as well as tumor initiation and progression in vivo. Furthermore, we demonstrated that CD147 promoted HNSCC progression through nuclear factor kappa B signaling. Therefore, we concluded that CD147 promoted tumor progression in HNSCC and might be a potential prognostic and treatment biomarker for HNSCC.

Can pattern and depth of invasion predict lymph node relapse and prognosis in tongue squamous cell carcinoma.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is a special type of oral cancer. Cervical lymph node relapse may occur in a large percentage of TSCC patients, which usually indicates poor prognosis. In this cohort study, we focused on the predictive value of the pathological features on cervical lymph node relapse and TSCC prognosis (disease free survival). METHODS: One hundred forty-one TSCC patients staged as T1-2N0 were enrolled and categorized. Subjects were followed-up for 60 months. Univariate analysis was performed with Chi-square test for cervical lymph node relapse and Kaplan-Meier survival analysis and log rank P value for patient prognosis; multivariate analysis was also utilized with Cox regression. RESULTS: In univariate analysis, trabes growth pattern, depth of invasion greater than 4 mm, poor pathological differentiation and neurovascular invasion were considered as risk factors for cervical lymph node relapse and poor prognosis. In multivariate analysis, only patients with trabes growth pattern in the invasive front or depth of invasion larger than 4 mm had a higher risk of metastasis. Elder age group and trabes growth pattern of invasive front were considered as predictors of poor prognosis. Bad habits of smoking and alcohol consumption were related to the higher risk of metastasis. CONCLUSION: Trabes growth pattern of invasive front was a potent risk factor for TSCC cervical lymph node relapse and indicated poor prognosis. Preventive therapy including selective neck dissection was thus suggested for certain patients. TRIAL REGISTRATION: Not applicable.

Circulating microRNA-21 as a biomarker for the detection of various carcinomas: an updated meta-analysis based on 36 studies.

Cancer is a class of diseases with high mortality rate, characterized by unregulated cell growth. Early diagnosis of cancer is currently the most effective method to prevent cancer development and improve the survival rate of patients. Traditional diagnostic methods such as biopsy usually provoke discomfort and unpleasant experience. Recently, microRNAs (miRNAs) were widely reported to be potential biomarkers to detect cancers without invasiveness. MicroRNA-21 (miRNA-21, miR-21) is one of the most prevalent miRNAs. This meta-analysis aims to make a comprehensive analysis of the potential role of circulating miR-21 as a biomarker in human carcinoma diagnosis. A total of 36 articles involving 2920 cancer patients and 1986 healthy controls with regard to the diagnostic value of the circulating miR-21 for cancer detection were selected from online bibliographic databases. For pooled analysis, the sensitivity, specificity, and other basic characteristics were extracted from the 36 included articles. Then, bivariate random-effects model was selected to gain pooled results. Furthermore, to explore the sources of heterogeneity, we conducted stratified and meta-regression analyses based on different race/sample groups. The pooled characteristics of all included articles were as follows: sensitivity, 0.78 (95% confidence intervals (CI), 0.73-0.82); specificity, 0.82 (95% CI, 0.79-0.86); positive likelihood ratio (PLR), 4.4 (95% CI, 3.6-5.4); negative likelihood ratio (NLR), 0.26 (95% CI, 0.21-0.33); diagnostic odds ratio (DOR), 17 (95% CI, 12-24); and area under the curve (AUC), 0.87 (95% CI, 0.84-0.90). The subgroup analyses results based on different ethnic populations revealed that the diagnostic accuracy of miR-21 tends to be higher in Asian populations than in Caucasian populations. Furthermore, another subgroup analysis performed on sample types suggested that the serum-based specimen used in cancer diagnosis appeared to be more accurate than the plasma-based specimen. Our meta-analysis shows that the circulating miR-21 may be a potential biomarker as diagnostic tool for early-stage cancer diagnosis.

[Expression of RACK1 and EGP40 in oral squamous cell carcinoma and its correlation with clinicopathological features and prognosis].

PURPOSE： To investigate the expression of tissue-active protein kinase C receptor 1 (RACK1) and epithelin glycoprotein 40 (EGP40) in oral squamous cell carcinoma (OSCC) and their relationship with clinicopathological features and prognosis. METHODS: A total of 103 patients with OSCC who were admitted to Shangrao People's Hospital from January 2016 to February 2019 were prospectively selected as the research subjects. All patients underwent radical resection of OSCC and were followed up for 3 years. Immunohistochemistry was used to detect the positive expression levels of RACK1 and EGP40 in cancer tissues and adjacent tissues. The positive expression of RACK1 and EGP40 in cancer tissues and adjacent tissues were compared. The relationship between the positive expression level of RACK1 and EGP40 in cancer tissues of OSCC patients and clinicopathological parameters was analyzed. Factors affecting postoperative recurrence and metastasis in OSCC patients were analyzed. The relationship between the expression of RACK1 and EGP40 in cancer tissues and postoperative disease-free survival of OSCC patients was analyzed. SPSS 18.0 software package was used for statistical analysis of the data. RESULTS: The positive expression rate of RACK1 and EGP40 in cancer tissues was significantly higher than those in adjacent tissues (P＜0.05). The positive expression rate of RACK1 and EGP40 in cancer tissues of OSCC patients with poorly differentiated, stage III, cervical lymph node metastasis, and infiltrating vessels was significantly higher than that in patients with moderate and high differentiation, stage II, no cervical lymph node metastasis, and no infiltrating vessels(P＜0.05). The positive expression rate of RACK1 in cancer tissue of OSCC patients in T3 stage was significantly higher than that in T2 stage(P＜0.05). Cox multivariate regression analysis showed pathological grade (RR=6.290, 95%CI: 2.588-15.287), cervical lymph node metastasis(RR=5.995, 95%CI: 2.467-14.571), RACK1 positive rate (RR=4.495, 95%CI: 1.850-10.925) and EGP40 positive rate (RR=4.559, 95%CI: 1.876-11.079) were factors affecting the recurrence and metastasis of OSCC patients after surgery(P＜0.05). The disease-free survival curve of patients with negative expression of RACK1 was significantly better than that of patients with positive expression (P＜0.05). The disease-free survival curve of patients with negative expression of EGP40 was significantly better than that of patients with positive expression (P＜0.05). CONCLUSIONS: The expression of RACK1 and EGP40 in cancer tissues of OSCC patients is related to clinicopathological parameters and prognosis. Patients with positive expression of RACK1 and EGP40 have a high risk of recurrence and metastasis after surgery.

[Treatment of maxillary ameloblastoma with different modalities: a retrospective analysis of 92 cases].

PURPOSE: To explore the appropriate surgical approach for each type of maxillary ameloblastoma. METHODS: The clinical data of 92 patients with maxillary ameloblastoma were retrospectively analyzed. All patients were pathologically diagnosed, followed up for 3-8 years after surgery, maxillofacial CT and panoramic images were taken regularly to observe the surgical outcomes. SPSS 22.0 software package was used for data analysis. RESULTS: The proportion of maxillary ameloblastoma in male and female patients was 3 to 1,with more male patients and the mean age was 45.77 years old. The total recurrence rate of 92 patients was 21.74%, among which unicystic ameloblastoma had no recurrence after different surgical procedures. Among 38 patients with typical maxillary ameloblastoma, 14 underwent curettage, 3 underwent decompression，16 underwent extended resection, 3 underwent subtotal maxillary resection, 1 underwent iliac bone transplantation after subtotal maxillary resection, and 1 underwent reconstruction with anterolateral thigh flap after subtotal maxillary resection. Among them, 18 had recurrence and 5 had canceration. Three patients with extrasseous/peripheral type underwent expanded resection and two underwent curettage，none of them had recurrence. One patient with metastasizing ameloblastoma recurred after extended resection. CONCLUSIONS: Maxillary ameloblastoma with unicystic type should be completely removed with minimal trauma. The recurrence rate of maxillary ameloblastoma via simple curettage or extended resection is still relatively high, which may be due to the large tumor involvement scope of these patients and the failure of complete tumor removal by curettage. For external/peripheral ameloblastoma and metastatic ameloblastoma, the involved jaw bone should be removed as much as possible to prevent recurrence. For malignant transformation of ameloblastoma, the tumor and jaw bone should be dissected during the operation to reduce recurrence rate. The primary site, cervical lymph nodes and lungs should be closely followed after operation to detect early metastasis.

N-cadherin protects oral cancer cells from NK cell killing in the circulation by inducing NK cell functional exhaustion via the KLRG1 receptor.

BACKGROUND: Circulating tumor cells (CTCs) can survive in the circulation and return to primary tumors through a self-seeding process. However, the mechanisms underlying CTCs escape from natural killer (NK) cell-mediated immune surveillance remain unclear. METHOD: Self-seeded tumor cells were isolated and characterized using a modified contralateral seeding model. A comparison of transcriptional profiles was performed between the parental cells and self-seeded cells. The molecular mechanism of self-seeded tumor cells escaping from NK cell was demonstrated through in vitro experiments and verified in a CTC-mimicking in vivo model. Then, the expression level of key protein mediating CTCs immune escape was detected in 24 paired primary and recurrent tumor samples of patients with oral cancer by the immunohistochemical method. RESULT: Self-seeded cells displayed resistance to NK cell-mediated lysis and a higher tumor seeding ability than their parental cells. Elevated expression levels of the CDH2 gene and its protein product, N-cadherin were found in self-seeded cells. NK cells secreted cytokines, and fluid shear stress facilitated N-cadherin release by promoting A disintegrin and metalloprotease 10 (ADAM10) translation or converting the precursor ADAM10 to the mature form. Soluble N-cadherin triggered NK cell functional exhaustion by interacting with the killer cell lectin-like receptor subfamily G member 1 (KLRG1) receptor and therefore protected tumor cells from NK cell killing in the circulation. In vivo experimental results showed that overexpression of N-cadherin promoted tumor self-seeding and facilitated the survival of CTCs. Compared with primary tumors, N-cadherin expression was significantly increased in matched recurrent tumor tissues. CONCLUSION: Together, our findings illustrate an unknown mechanism by which CTCs evaded NK cell-mediated immune surveillance, and indicate that targeting N-cadherin is an effective strategy to prevent CTCs from homing to primary tumor.

M1-like tumor-associated macrophages cascade a mesenchymal/stem-like phenotype of oral squamous cell carcinoma via the IL6/Stat3/THBS1 feedback loop.

BACKGROUND: Tumor-associated macrophages (TAMs) have a leading position in the tumor microenvironment. Previously, we have demonstrated that M1-like TAMs activated by exosome-transferred THBS1 promote malignant migration in oral squamous cell carcinoma (OSCC). However, the functional roles and associated molecular mechanisms of the activated M1-like TAMs need to be further clarified in OSCC. METHODS: Conditioned Media (CM) were harvested from the exosome activated M1-like TAMs. We measured the malignant behaviors of OSCC under the treatment of CM from M1-like TAMs by performing colony forming assays, invasion assays, wound-healing assays, spheroid forming assays and in vivo xenograft experiments. The underlying mechanisms were investigated by RNA-seq, cytokines analysis, intracellular signaling pathway analysis, ChIP assays, bioinformatics analysis and validation. RESULTS: M1-like TAMs significantly promoted the epithelial-mesenchymal transition (EMT) process, and induced the cancer-stem like cells (CSCs) by upregulating the expression of MME and MMP14 in OSCC cells. Cytokine analysis revealed a shark increase of IL6 secretion from M1-like TAMs. Blocking IL6 in the CM from M1-like TAMs could significantly weaken its effects on the colony forming, invasion, migration, microsphere forming and xenograft forming abilities of OSCC cells. Cellular signaling assays indicated the activation of Jak/Stat3 pathway in the OSCC cells treated by the CM from M1-like TAMs. Blocking the activation of the Jak/Stat3 pathway could significantly weaken the effects of M1-like TAMs on the colony forming, invasion, migration, microsphere forming and xenograft forming abilities of OSCC cells. Further RNA-seq analysis and bioinformatics analysis revealed an increased expression of THBS1 in the OSCC cells treated by M1-like TAMs. Bioinformatics prediction and ChIP assays revealed the activation of Stat3 by CM from M1-like TAMs could directly promote the transcription of THBS1 in OSCC cells. CONCLUSIONS: We proposed that M1-like TAMs could cascade a mesenchymal/stem-like phenotype of OSCC via the IL6/Stat3/THBS1 feedback loop. A better understanding on the functional roles and associated molecular mechanisms of M1-like TAMs might facilitate the development of novel therapies for supplementing the current treatment strategies for OSCC patients.

Second primary oral squamous cell carcinoma after radiotherapy: a retrospective cohort study.

BACKGROUND: The purpose of the present study was to investigate the clinicopathological characteristics and prognostic factors of second primary oral squamous cell carcinoma after radiotherapy for head and neck cancer. METHODS: The clinicopathological characteristics of 48 second primary oral squamous cell carcinoma patients with a history of radiotherapy for head and neck cancer were retrospectively analyzed by Kaplan-Meier survival analysis and Cox proportional hazards model, including gender, age, alcohol consumption, smoking, clinical stage, margin status, regional lymph node status, tumor differentiation and treatment mode. RESULTS: The second primary oral squamous cell carcinoma mostly occurred on the tongue [18/48], buccal [12/48] and gingiva [10/48], and the 3- and 5-year overall survival (OS) was 60.3% and 39.4%, respectively. Margin status and extranodal extension were significantly associated with OS, while only margin status was found to be an independent prognostic factor of OS in the Cox proportional hazards model (P=0.003, HR =3.976, 95% CI: 1.596-9.904). CONCLUSIONS: Oral squamous cell carcinoma patients underwent radiotherapy for head and neck cancer show poor survival outcomes. Margin status is an independent prognostic factor of second primary oral squamous cell carcinoma.

Periostin secreted by cancer-associated fibroblasts promotes cancer stemness in head and neck cancer by activating protein tyrosine kinase 7.

Protein tyrosine kinase 7 (PTK7) and cancer-associated fibroblasts (CAFs) play important roles in cancer stemness, respectively. However, little is known about interaction between CAFs and PTK7 in cancers. In this study, we showed that PTK7 was significantly correlated with the Wnt/ß-Catenin pathway and aggressive clinicopathologic features in human head and neck squamous cell carcinoma (HNSCC). Meanwhile, animal experiments showed that PTK7 enhanced chemoresistance and lung metastasis of HNSCC in vivo. In addition, co-immunoprecipitation (co-IP) assay demonstrated that POSTN secreted by CAFs was a potential upstream ligand of PTK7 which might act as a receptor. Further analysis revealed that POSTN promoted the cancer stem cell (CSC)-like phenotype via PTK7-Wnt/ß-Catenin signaling, including the proliferation and invasion of HNSCC cells in vitro, as well as tumor initiation and progression in vivo. Collectively, our study proved that CAF-derived POSTN might promote cancer stemness via interacting with PTK7 in HNSCC, suggesting that the combination of POSTN and PTK7 might be a potential prognostic and diagnostic indicator and a  promising therapeutic target.

Prognostic impact of perineural invasion in early stage oral tongue squamous cell carcinoma: Results from a prospective randomized trial.

BACKGROUND: Although perineural invasion (PNI) has been recognized as a poor prognostic factor for oral cancer, few studies have focused on tongue squamous cell carcinoma (TSCC). Using a prospective randomized trial, this study investigated the role of PNI in the regional control and survival of the patients with cT1-2N0 TSCC, and clarified the benefit of neck management based on PNI status. METHODS: PNI status was reviewed under H&E staining in tumors of 221 patients with cT1-2N0 TSCC, who were randomly assigned into elective neck dissection (END) group (n = 111) and observation group (n = 110). Oncologic and survival outcomes were analyzed by multivariate regression and Kaplan-Meier analyses. RESULTS: PNI was identified in 34 patients and multivariate analyses revealed that PNI remained an independent predictor for cervical lymph node metastasis (CLNM), local relapse, neck relapse and disease-specific survival (DSS) after controlling for T stage and pathologic differentiation. END could not improve the benefit for patients. Stratified analysis revealed that END also could not improve neck control or DSS among patients with PNI. CONCLUSIONS: This study demonstrated that PNI was an invaluable pathological parameter to independently predict cervical metastasis, local relapse, neck relapse and poor survival outcomes, but END could not improve benefits compared to observation for the PNI-positive patients.

MFAP5 and TNNC1: Potential markers for predicting occult cervical lymphatic metastasis and prognosis in early stage tongue cancer.

The purpose of this study is to identify candidate genes that could predict prognosis of early-stage tongue squamous cell carcinoma (TSCC) and its occult cervical lymphatic metastasis by large-scale gene expression profiling. Tumor tissue and matched normal mucosa samples were collected from patients with TSCC and analyzed with Affymetrix HTA2.0 high-density oligonucleotide array. Differentially expressed genes in TSCC with cervical lymph node metastasis (CLNM) were further analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for their functions and related pathways. A total of 107 differentially expressed genes (p < 0.05) were identified by microarray in TSCC samples with CLNM (n = 6) compared to those without CLNM (n = 6). Genes involved in the cell-matrix adherens junction and migration function including MFAP5, TNNC1, MGP, FBFBP1 and FBXO32 were selected and validated by RT-PCR in TSCC samples (n = 32). Of the five genes, MFAP5 and TNCC1 expressions were further validated by immohistochemistry (n = 61). The significant positive correlation between MFAP5 and TNNC1 expression (p<0.001) was observed. Notably, over-expression of MFAP5 and TNNC1 were correlated with CLNM, metastasis relapse-free survival and overall survival. Our findings indicated that MFAP5 and TNNC1 may be potential markers for predicting occult cervical lymphatic metastasis and prognosis of oral tongue carcinoma.

Neurovascular Invasion and Histological Grade Serve as the Risk Factors of Cervical Lymph Node Metastases in Early Tongue Squamous Cell Carcinoma.

The objectives of this study were to analyze the regional characteristics of the cervical lymph node metastasis and to investigate the factors associated with the risk of lymph node involvement. One hundred seventy-one patients suffering from early primary squamous cell carcinoma (SCC) of the tongue (cT1-2N0) were enrolled. Gender, age, growth site, T stage, histological grade, and neurovascular invasion were statistically analyzed by K-M survival analysis and Cox multivariate analysis to evaluate the relationship between the factors and the neck lymph node metastasis. Of the 171 cases divided into the neck dissection group and observation group, 40 ended up with lymph node metastasis, of which 17 were metastasized to level I, 27 to level II, 10 to level III, 2 to level IV, and 1 to level V. Histological grade and neurovascular invasion were significantly associated with lymph node involvement in univariate and multivariate analyses. Age distribution was found to be significantly associated with the lymph node metastasis in multivariate analysis. The metastasis of early tongue SCC has a certain regularity at different sites. Age was not a critical risk factor for cervical lymph node metastasis after surgery. Tumor size was suspected to exert a negative effect on metastasis by influencing tumor invasion. Histological grade and neurovascular invasion were significantly associated with the risk of cervical lymph node metastasis of early tongue SCC.