Xiao-mei Lao

Zoledronate suppressed angiogenesis and osteogenesis by inhibiting osteoclasts formation and secretion of PDGF-BB

Purpose Bisphosphonates related osteonecrosis of jaw (BRONJ) is a severe complication of systemic BPs administration, the mechanism of which is still unclarified. Recently, platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts was reported to promote angiogenesis and osteogenesis. This study aimed to clarify whether bisphosphonates suppressed preosteoclasts releasing PDGF-BB, and whether the suppression harmed coupling of angiogenesis and osteogenesis, which could contribute to BRONJ manifestation. Methods and results Zoledronate significantly inhibited osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining and PDGF-BB secretion tested by ELISA. In line with decreasing secretion of PDGF-BB by preosteoclasts exposed to zoledronate, conditioned medium (CM) from the cells significantly induced less migration of endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) compared to CM from unexposed preosteoclasts. Meanwhile, angiogenic function of EPCs and osteoblastic differentiation of MSCs also declined when culturing with CM from preosteoclasts treated by zoledronate (PZ-CM), evidenced by tube formation assay of EPCs and alkaline phosphatase activity of MSCs. Western blot assay showed that the expression of VEGF in EPCs and OCN, RUNX2 in MSCs declined when culturing with PZ-CM compared to CM from preostoeclasts without exposure of zoledronate. Conclusion Our study found that zoledronate was able to suppress preosteoclasts releasing PDGF-BB, resulting in suppression of angiogenesis and osteogenesis. Our study may partly contributed to the mechanism of BRONJ.

Maxillary reconstruction assisted by preoperative planning and accurate surgical templates

OBJECTIVE Surgical reconstruction of maxilla is technically challenging and time consuming. The study reports a new method of maxillary reconstruction assisted by preoperative surgical simulation and accurate transferring templates. STUDY DESIGN Six patients requiring maxillary reconstruction were enrolled in our study. Templates of maxillary resection, fibula cutting, and positioning were designed based on computed tomography (CT) data and fabricated via rapid prototyping technique. Resection, fibula cutting, and positioning were performed according to the templates. Accuracy was evaluated by measuring deviation, performed by superimposing preoperative planning and postoperative maxilla. RESULTS The surgery was performed faithfully to the preoperative planning. The facial contour was satisfied. Postoperative CT scans showed high accuracy of the surgical implementation. The average central point deviation, maximum deviation, and rotation were 0.58 mm, 1.53 mm, and 6.0°, respectively. CONCLUSION With preoperative surgical simulation and templates, maxillary reconstruction can be performed accurately.

Genome-wide analysis of cancer cell-derived Foxp3 target genes in human tongue squamous cell carcinoma cells

The forkhead transcription factor Foxp3 is essential for differentiation and activation of regulatory T cells (Tregs), and used to be regarded as specific transcription factor of Tregs. In recent years, Foxp3 expression in tumor cells (cancer cell-derived Foxp3) has gained great interest, but its function and molecular mechanisms remain incompletely understood. In the present study, we detected dynamic nuclear translocation of Foxp3 in TSCC cells using immunofluorescent staining. Then we performed a genome-wide analysis of Foxp3 in TSCC cells using a combination of ChIP-on-chip and whole-genome microarray assays. We also compared Foxp3 biding sites in TSCC cells with the known binding sites in human Tregs to show the differences in transcriptional regulation profile. Results indicate that Foxp3 in TSCC cells has distinct biological functions compared with that in Tregs. Cancer cell-derived Foxp3 directly regulates the transcription of genes that affect certain internal biological processes of TSCC cells, and indirectly influences the extracellular microenvironment. This study reveals the relationship between direct and indirect targets genes of Foxp3 in TSCC cells and provide molecular basis of cancer cell-derived Foxp3 function.

miRNA‑335 and miRNA‑182 affect the occurrence of tongue squamous cell carcinoma by targeting survivin

The aim of the present study was to characterize the roles of two microRNAs (miRs) that have been reported to be differentially expressed in tongue squamous cell carcinoma (TSCC), miR-335 and miR-182. In total, 20 tumor tissue samples and 20 corresponding adjacent non-cancerous samples were collected from patients with TSCC to measure the expression of miR-335 and miR-182 and the potential shared target of these miRs, survivin, using reverse transcription-quantitative polymerase chain reaction and western blotting. In the TSCC tissue samples, significantly decreased expression of the two miRs and increased expression of survivin were detected compared with adjacent non-cancerous controls. Subsequently, it was confirmed that survivin was the target gene of miR-335 and miR-182 using a luciferase assay in TSCC cells. In order to examine the function of miR-335 and miR-182 in the development of TSCC, TSCC cells were transiently transfected with the mimics of the two miRs, and it was confirmed that the introduction of miR-335 and miR-182 to cells suppressed the expression of survivin and markedly inhibited the proliferation of the TSCC cells. Furthermore, miR-335 and miR-182 were found to induce cell cycle arrest by suppressing the expression of survivin. The present study revealed a negative regulatory role of miR-335 and miR-182 in the proliferation of TSCC cells by targeting survivin, and miR-335 and miR-182 may be novel therapeutic targets for the treatment of TSCC.

Neck observation versus elective neck dissection in management of clinical T1/2N0 oral squamous cell carcinoma: a retrospective study of 232 patients

Objective The management of early-stage (cT1/2N0) oral squamous cell carcinoma (OSCC) remains a controversial issue. The aim of this study was to compare the clinical outcomes of neck observation (OBS) and elective neck dissection (END) in treating patients with cT1/2N0 OSCC. Methods A total of 232 patients with cT1/2N0 OSCC were included in this retrospective study. Of these patients, 181 were treated with END and 51 with OBS. The survival curves of 5-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates were plotted using the Kaplan-Meier method for each group, and compared using the Log-rank test. Results There was no significant difference in 5-year OS and DSS rates between END and OBS groups (OS: 89.0% vs. 88.2%, P=0.906; DSS: 92.3% vs. 92.2%, P=0.998). However, the END group had a higher 5-year RFS rate than the OBS group (90.1% vs. 76.5%, P=0.009). Patients with occult metastases in OBS group (7/51) had similar 5-year OS rate (57.1% vs. 64.1%, P=0.839) and DSS rate (71.4% vs. 74.4%, P=0.982) to those in END group (39/181). In the regional recurrence patients, the 5-year OS rate (57.1% vs. 11.1%, P=0.011) and DSS rate (71.4% vs. 22.2%, P=0.022) in OBS group (7/51) were higher than those in END group (9/181). Conclusions The results indicated that OBS policy could obtain the same 5-year OS and DSS as END. Under close follow-up, OBS policy may be an available treatment option for patients with clinical T1/2N0 OSCC.

Elevated hydrostatic pressure promotes ameloblastoma cell invasion through upregulation of MMP-2 and MMP-9 expression via Wnt/β-catenin signalling

BACKGROUND The process of marsupialization involves the release of intracystic pressure and the fluid contained within. Marsupialization of cystic ameloblastoma is controversial; therefore, we investigated how hydrostatic pressure influences biological behaviours of ameloblastoma cells and its underlying mechanisms. MATERIALS AND METHODS An ameloblastoma epithelial cell line, hTERT+ -AM, was exposed to different hydrostatic pressures with or without Dickkopf-related protein 1 (also known as DKK), a canonical Wnt signalling pathway inhibitor. A CCK-8 assay, a monolayer wound assay, and a Transwell assay were used to determine cell proliferation, migration and invasion, respectively. qRT-PCR and Western blot were used to detect expression of MMP-2, MMP-9, RANKL and other downstream targets of Wnt signalling. RESULTS Elevated hydrostatic pressure promoted migration and invasion of ameloblastoma cells, but inhibited proliferation. Expression of MMP-2, MMP-9, LEF-1, cyclin D1, c-Jun and c-Myc was significantly upregulated under elevated hydrostatic pressure, and these effects could be abolished by DKK1. Expression of RANKL, which is thought to be a downstream target of Wnt signalling, did not significantly change under elevated hydrostatic pressure. CONCLUSIONS This study indicates that elevated hydrostatic pressure promotes the migration and invasion of ameloblastoma cells by activating the Wnt/β-catenin pathway, thereby increasing expression of MMP-2, MMP-9 and other Wnt signalling downstream targets. This suggests that marsupialization may reduce invasiveness and reverse the bone resorption process by lowering intracystic hydrostatic pressure in cystic ameloblastoma.

Marsupialization of mandibular cystic ameloblastoma: Retrospective study of 7 years

This retrospective study investigated the reduction rate and speed of shrinkage after marsupialization in mandibular cystic ameloblastoma and clarified whether marsupialization is appropriate for unicystic ameloblastoma and multicystic ameloblastoma.

Interaction of cancer cell-derived Foxp3 and tumor microenvironment in human tongue squamous cell carcinoma

&NA; The forkhead transcription factor, Foxp3, has been proved essential for differentiation and activation of regulatory T cells (Tregs). Recently, Foxp3 expression in tumor cells (cancer cell‐derived Foxp3) has gained increasing interest, but the function has yet to be confirmed. In the current investigation, we identified the interaction of cancer cell‐derived Foxp3 and tumor microenvironment in human tongue squamous cell carcinoma(TSCC) by various in vitro methods. We detected cancer cell‐derived Foxp3 was closely associated with the infiltration of Foxp3 + lymphocytes in TSCC lesions using immunohistochemical staining. The cytokines secretion (IFN‐&ggr;, TGF&bgr;, IL‐2, IL‐6, IL‐1&bgr;, IL‐10, IL‐8, IL‐17, IL‐23) of PBMC and differentiation of CD4 +T cells were modulated by the expression of Foxp3 in TSCC, shown by ELISA and flow cytometry. As feedback, increasing TGF&bgr; and decreasing IL‐17 further up‐regulated cancer cell‐derived Foxp3. Furthermore, CHIP on chip assay showed that both TGF&bgr; and IL‐17 decreased the number of Foxp3‐binding genes in TSCC. GO and pathway analysis suggested that, treated with TGF&bgr; or Th17, Foxp3‐binding genes were inclined to the negative regulation of TGF&bgr; signal pathway. Taken together, this study showed cancer cell‐derived Foxp3 contributed to Tregs expansion in TSCC microenvironment with positive and negative feedbacks. HighlightsCancer cell‐derived Foxp3 modulates cytokines levels in TSCC microenvironment.Cancer cell‐derived Foxp3 modulates differentiation of CD4 +T cells.Feedback between TGF&bgr;, IL‐17 and cancer cell‐derived Foxp3 gradually increased TGF&bgr;.Foxp3 in TSCC contributed to Tregs expansion with positive and negative feedbacks.