Jinsong Hou

Application of CAD/CAM-assisted technique with surgical treatment in reconstruction of the mandible.

OBJECTIVE The purpose of this clinical study was to explore the optimal method of reconstruct mandible defects individually and immediately. STUDY DESIGN Three-dimensional model simulation technique and vascularized fibular osteomyocutaneous flap were used to repair 15 cases of mandible defects, which were caused by ameloblastoma. A three-dimensional computed tomography (CT) images were converted to a virtual model using CAD software and the 3-dimensional (3D) simulated resin models of skeleton and fibula were used to design the osteotomies, bone segment replacement and titanium mesh shaping preoperatively. RESULTS Fibula flaps were alive and no complication occurred. The patients were satisfied with the results both esthetically and functionally. CONCLUSIONS This preliminarily clinical study and case demonstrated that CAD/CAM-assisted technique with surgical treatment offers an individual anatomical reconstruction of the mandible in ameloblastoma patients. The procedures guarantee intraoperatively an exact placement of the preformed mesh even for precise reconstruction of extensive mandible defects.

Tumor budding correlates with occult cervical lymph node metastasis and poor prognosis in clinical early-stage tongue squamous cell carcinoma.

BACKGROUND Tumor budding has been suggested to be a prognostic factor in various human cancers. However, the prognostic value of tumor budding for early-stage (cT1/2N0) tongue squamous cell carcinoma remains inconclusive. This study analyzed the correlation of tumor budding with the clinicopathologic features, and its prognostic significance for cT1/2N0 stage tongue squamous cell carcinoma. METHODS One hundred and ninety-five patients with T1/2 stage tongue squamous cell carcinoma enrolled in the retrospective study. Tumor invasive depth, the intensity of tumor budding, and other clinicopathological features were reviewed. Overall survivals were evaluated by the Kaplan-Meier method. For multivariable analysis, Coxs proportional hazards regression models were performed. RESULTS The frequency of tumor buds in tongue squamous cell carcinoma is about 85.6% in this study. The intensity of tumor budding showed strong correlations with occult lymph node metastasis (P < 0.05), local relapse (P < 0.01), worse invasive pattern (P < 0.01), and invasive depth (P < 0.05). The invasive depth was significantly associated with T classification (P < 0.01) and lymph node metastasis (P < 0.01). And both high intensity of tumor budding and deeper invasive depth correlated with reduced overall survival. Coxs regression models proved tumor budding to be an independent prognostic factor in clinical early-stage tongue squamous cell carcinoma. Tumor local relapses were also a predictor of tongue squamous cell carcinoma progression. CONCLUSIONS Tumor budding is a frequent event in tongue squamous cell carcinoma. It independently predicted prognosis of patients with T1/2 stage tongue squamous cell carcinoma and may be used for routing pathological diagnosis and the decision of elective lymph node dissection.

Pingyangmycin sclerotherapy for infantile hemangiomas in oral and maxillofacial regions: an evaluation of 66 consecutive patients.

The management of infantile hemangiomas remains a subject of controversy. The purpose of this study was to investigate the indications and treatment results of intralesional injection of pingyangmycin for treatment of infantile hemangiomas. In a prospective study of 66 patients, the effectiveness of intralesional injection of pingyangmycin was evaluated and documented. The lesions were all located in the oral and maxillofacial regions. The smallest lesion was 1.0 cm × 0.7 cm and the largest was 4.6 cm × 3.8 cm. Amongst the 66 infants who underwent sclerotherapy with pingyangmycin, cure was obtained in 74% (49/66) of patients, marked improvement of the treated lesion occurred in 14% (9/66), improvement occurred in 12% (8/66), and a lack of response was not observed in any patient. All patients were regularly followed up for 1-4 years following pingyangmycin treatment, and they demonstrated the same good results over this time. Intralesional injection of pingyangmycin was a reliable and effective therapeutic choice for infantile oral and maxillofacial hemangiomas, as it shortened the involution time and decreased the influence induced by these potentially countenance-influenced tumours with few complications.

Beclin1 inhibits proliferation, migration and invasion in tongue squamous cell carcinoma cell lines

OBJECTIVES The role of autophagy is still a controversy in cancer development. In our previous study, we confirmed that decrease of autophagy activity promotes malignant progression of tongue squamous cell carcinoma (TSCC). However, the role of autophagy-related protein, Beclin1, has not well been documented in TSCC. In this study, we aim to elucidate the role of beclin1 in TSCC progression and investigate its potential mechanisms. MATERIALS AND METHODS TSCC cell lines, SCC9 and SCC15 were used to generate the stable cells with transfection lentivirus BECN1 and sh-BECN1. Then, Beclin1 expression was detected with qPCR and western blot. Moreover, the expressions of autophagy-related proteins and tumor metastasis associated proteins were examined by western blot and ELISA. For functional analysis, MTT assay were performed to evaluate the proliferation activity and transwell assay was used to assess the migration and invasion ability. Finally, TSCC xenograft models were established to confirm the effect of Beclin1 on TSCC in vivo. RESULTS The results showed that BECN1 and sh-BECN1 virus transfection significantly increased or decreased the mRNA and protein expression of Beclin1 in the transfected TSCC cells. Meanwhile, we also observed that Beclin1 could enhance the expression levels of LC3-II, ATG4 and ATG5. Then, we revealed that overexpression of Beclin1 inhibited proliferation, migration and invasion while knockdown of Beclin1 promoted proliferation, migration and invasion in TSCC cells. Furthermore, we demonstrated that vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 and -9 were involved in Beclin1-mediated inhibition of migration and invasion. More importantly, our data also confirmed that Beclin1 inhibited TSCC xenograft growth in vivo. CONCLUSION Taken together, the results indicate that autophagy regulating gene, Beclin1, may contribute to the malignant phenotypes of TSCC cells and can be a potential target for oral cancer gene therapy.

miR-373-3p Targets DKK1 to Promote EMT-Induced Metastasis via the Wnt/β-Catenin Pathway in Tongue Squamous Cell Carcinoma.

MicroRNAs (miRNAs) regulate gene expression and at the same time mediate tumorigenesis. miR-373-3p has diverse effects in tumors, but its role in tongue squamous cell carcinoma (TSCC) remains unknown. The purpose of this study is to determine the function of miR-373-3p in the progression of TSCC. Our results brought to light that miR-373-3p is markedly upregulated in clinical TSCC tissues compared with paired adjacent normal tissues and has significant correlation with a more aggressive TSCC phenotype in patients. Gain-of-function and loss-of-function studies revealed that ectopic miR-373-3p overexpression promoted the metastasis of TSCC cells. Notably, Wnt/β-catenin signaling was hyperactivated in TSCC cells overexpressing miR-373-3p, and this pathway was responsible for the epithelial-mesenchymal transition (EMT) induced by miR-373-3p. Furthermore, miR-373-3p directly targeted and suppressed Dickkopf-1 (DKK1), a negative regulator of the Wnt/β-catenin signaling cascade. These results demonstrate that, by directly targeting DKK1, miR-373-3p constitutively activated Wnt/β-catenin signaling, thus promoting the EMT-induced metastasis of TSCC. Taken together, our findings reveal a new regulatory mechanism for miR-373-3p and suggest that miR-373-3p might be a potential target in TSCC therapy.

MicroRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway

Accumulating data suggest that microRNAs (miRNAs) play a pivotal role in the regulation of tumor cell sensitivity to chemotherapeutic agents. Although the roles of a few miRNAs have been identified in cisplatin resistance, little is known in regards to the concerted contribution of miRNA-mediated biological networks. In the present study, we demonstrated that microRNA-218 (miR-218) was significantly upregulated in cisplatin-resistant oral cancer cells. The results of cell viability and apoptosis assay showed that ectopic expression of miR-218 induced cell survival and resistance to cisplatin, whereas suppression of miR-218 caused apoptosis and enhanced sensitivity to cisplatin. Moreover, we identified PPP2R5A as a new direct target of miR-218 by using the dual luciferase reporter assay. Overexpression of miR-218 led to inhibition of PPP2R5A expression, whereas knockdown of miR-218 increased PPP2R5A levels. Introduction of PPP2R5A abrogated miR-218-mediated cell survival and drug resistance. Furthermore, suppression of miR-218 or PPP2R5A significantly promoted or reduced cisplatin-induced apoptosis, respectively. Finally, PPP2R5A overexpression or β-catenin knockdown inhibited miR-218-mediated Wnt activation and partially restored cell sensitivity. Our data revealed a molecular link between miR-218 and PPP2R5A/Wnt signaling and implicates miR-218 as a potential target for oral cancer therapy.

Interplay between ΔNp63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma

TP63 acts as a master regulator in epithelia development and in the progression of various cancers, but its role in oral cancer pathogenesis remains unknown. This study aimed to explore the role of TP63 in the progression of oral squamous cell carcinoma (OSCC). This study shows that ΔNp63, the predominant isoform of TP63, is significantly upregulated in OSCC tissues and cell lines compared with their normal counterparts, and its expression is closely correlated with pathological differentiation, lymph node metastasis and clinical stage in patients with OSCC. The overexpression of ΔNp63 promotes growth, metastasis and stem-like properties in OSCC cells, and ΔNp63 depletion significantly represses OSCC cellular phenotypes in vitro and in vivo. The ΔNp63 isoform transcriptionally suppresses miR-138-5p expression; restoration of miR-138-5p expression partially abolishes the effect of upregulating ΔNp63. This study also demonstrates that miR-138-5p directly targets ΔNp63, resulting in crosstalk with ΔNp63. The correlation between ΔNp63 and miR-138-5p was further validated in OSCC tissues and was found to be significantly associated with the prognosis of patients with OSCC. Therefore, our data reveal that the interplay between ΔNp63 and miR-138-5p promotes OSCC progression by regulating cell growth, metastasis and stemness.

Activation of adrenergic receptor β2 promotes tumor progression and epithelial mesenchymal transition in tongue squamous cell carcinoma

Tongue squamous cell carcinoma (TSCC) is more aggressive than other cancers in the head and neck region because of its potential for metastasis. Recently, β2-adrenergic receptor (β2-AR) has been reported to be a potential promoter in various types of solid cancer. However, the role of β2-AR and its effect on TSCC is not well documented. Histological staining, western blot analysis, migration and invasion assay were used. In this study, the expression of β2-AR was increased in TSCC tissue compared with adjacent non-cancerous epithelium. Further analysis demonstrated that increased expression of β2-AR was correlated with differentiation, lymph node metastasis and reduced overall survival rate in patients with TSCC. In vitro studies confirmed that activation of β2-AR can promote epithelial mesenchymal transition in TSCC by initiating an interleukin-6/Stat3/Snail1 pathway. These results suggest that β2-AR has an oncogenic role in TSCC and may be a potential therapeutic target in TSCC.

Silencing PFKP inhibits starvation-induced autophagy, glycolysis, and epithelial mesenchymal transition in oral squamous cell carcinoma

ABSTRACT The tumor starvation microenvironment plays a pivotal role in the malignant progression of cancer, which is closely related to autophagy, glycolysis, and epithelial mesenchymal transition (EMT). Nevertheless, the underlying mechanisms of the starvation‐mediated malignant phenotype are still not well documented. In this study, we aimed to investigate the effect of starvation on glycolysis, autophagy, and EMT in OSCC and to further elucidate the key metabolic modulator. The results showed that starvation can induce autophagy, EMT, and enhanced glycolysis in OSCC cells. We determined that the expression of the key glycolytic enzyme phosphofructokinase‐platelet (PFKP) obviously increased under starvation conditions and that PFKP knockdown inhibited starvation‐mediated glycolysis, autophagy and EMT in OSCC cells. Moreover, we confirmed that PFKP knockdown inhibited OSCC xenograft growth in vivo. In addition, PFKP expression was significantly increased in OSCC patients and its upregulation was associated with the presence of tumor pathological differentiation and lymph node metastasis. Taken together, our findings demonstrate that PFKP is necessary for starvation‐mediated autophagy, glycolysis, and EMT, thereby promoting the malignant progression of OSCC. HIGHLIGHTSThe effect of starvation on glycolysis, autophagy and EMT in OSCC.We verified the PFKP higher expression under starvation condition.PFKP modulates starvation mediated glycolysis, autophagy, EMT of OSCC.PFKP knockdown inhibits OSCC xenograft tumor growth.The role of PFKP on clinicopathology in the progression of OSCC.

Deregulation of Hexokinase II Is Associated with Glycolysis, Autophagy, and the Epithelial-Mesenchymal Transition in Tongue Squamous Cell Carcinoma under Hypoxia

The glycolytic enzyme Hexokinase (HKII) participates in tumor glycolysis and the progression of various cancers, but its clinicopathological effect on the progression of tongue squamous cell carcinoma (TSCC) and its role in glycolysis, autophagy, and the epithelial-mesenchymal transition of TSCC in a hypoxic microenvironment remain unknown. Our results showed that HKII expression was dramatically increased in TSCC tissues and that its upregulation was significantly associated with the presence of pathological differentiation, lymph node metastasis, and clinical stage. The level of autophagy-specific protein LC3, EMT-related proteins, and the migration and invasion capabilities of TSCC cells all increased under hypoxia. Moreover, hypoxia increased the glucose consumption and lactate production of TSCC cells, and we demonstrated that the expression of the glycolytic key gene HKII was significantly higher than in that of the control group. Notably, the downregulation of HKII resulted in a significant decrease of TSCC cell glucose consumption lactate production and autophagic activity during hypoxia. HKII knockdown blocked the migratory and invasive capacity of TSCC cells and we specifically determined that the EMT ability decreased. Therefore, our findings revealed that the upregulation of HKII enhanced glycolysis and increased autophagy and the epithelial-mesenchymal transition of tongue squamous cell carcinoma under hypoxia.