Delin Lei

Tisssue responses in corticotomy- and osteotomy-assisted tooth movements in rats: histology and immunostaining.

INTRODUCTION The purpose of this histologic study was to examine underlying cellular responses to corticotomy- and osteotomy-assisted tooth movements. METHODS Thirty-six rats were divided into 5 groups: corticotomy-assisted tooth movement (CO + TM), sham corticotomy without tooth movement (CO alone), osteotomy-assisted tooth movement (OS + TM), sham osteotomy without tooth movement (OS alone), and unassisted tooth movement (TM alone). Standard orthodontic springs were activated to produce mesial tooth movement. The rats were killed at 3, 21, and 60 days after activation for osteoclast and blood vessel counts, and immunostaining with proliferating cell nuclear antigen (PCNA), transforming growth factor beta 1 (TGF beta 1), vascular endothelial growth factor (VEGF), and osteocalcin were performed. RESULTS The CO + TM group had significantly more osteoclasts at 3 days (P <0.005) compared with the OS + TM group. The alveolar bone surrounding the dental roots was replaced with multicellular tissue at 21 days in the CO + TM group but was intact in the OS + TM group with the exception of a distal distraction site. At day 21, immunostaining with PCNA, TGF beta 1, VEGF, and osteocalcin occurred at the mesial border of bone in the CO + TM group, whereas a diffuse pattern was observed in the distal distraction sites at 21 and 60 days in the OS + TM group. CONCLUSIONS Corticotomy-assisted tooth movement produced transient bone resorption around the dental roots under tension; this was replaced by fibrous tissue after 21 days and by bone after 60 days. Osteotomy-assisted tooth movement resembled distraction osteogenesis and did not pass through a stage of regional bone resorption.

Bleomycin A5 sclerotherapy for cervicofacial lymphatic malformations

OBJECTIVES The purpose of this study was to document the results of bleomycin A5 sclerotherapy for cervicofacial lymphatic malformations (LMs), and the clinical data of 65 patients between October 2004 and October 2007 were reviewed. METHODS Of the 65 patients in the study, 60 patients were given intralesional injection of bleomycin A5. Five patients underwent partial resection, and then an injection of bleomycin A5 for the remaining lesion. The outcomes were assessed by physical examination and Doppler ultrasonography scan. The follow-up time was from 6 months to 3 years after the last injection (mean, 16 months). RESULTS Among the 65 patients, 41 were men and 24 were women (1.7:1 male:female ratio), the age range was 3 months to 45 years (mean, 12 years). Thirty-two lesions (49%) were macrocystic, 30 (46%) were microcystic, and 3 (5%) were combined. Each patient received 1 to 10 injections (mean, 3.0 injections) for the whole course of treatment, and the total dose of bleomycin A5 was from 8 to 80 milligrams (mean, 24.0 mg). Twenty-six of 32 macrocystic lesions (81%) showed greater than 90% reduction, whereas another 6 (19%) exhibited 50% to 90% reduction. Nineteen of 30 microcystic lesions (63%) showed greater than 90% reduction; 10 (33%) had 50% to 90% reduction; and 1 (4%) had less than 50% size reduction. Of the 3 combined lesions, 2 (67%) had greater than 90% shrinkage, and 1 (3%) had less than 50% reduction. The complications included ulceration of oral mucosa, minor soft tissue atrophy, mild fever, and hematoma. There was no recurrence throughout the follow-up period. CONCLUSION These data suggest bleomycin A5 is a safe and effective intralesional agent for the treatment of macrocystic LMs, superficial oral mucosa LM, and localized deep microcystic lesions. For extensive macrocystic LMs involving contiguous anatomic areas and diffuse microcystic lesions involving deep tissues, bleomycin A5 injection combined with resection is necessary.

Diagnosis and management of intraparotid facial nerve schwannoma

OBJECTIVE Our objective was to provide the management guidelines for facial nerve schwannomas (FNSs) presenting as a parotid mass. STUDY DESIGN The study is a case report and literature review. METHODS Four clinical cases of patients with an asymptomatic parotid mass diagnosed as FNS are presented. The patients presentation, the diagnostic algorithm and surgical rationale are discussed. A review of the literature on FNSs is presented. CONCLUSIONS Intraparotid FNSs are an extremely rare entity and are rarely diagnosed preoperatively. Intraoperatively, conservative biopsy in a non-functional part of the lesion can be used to make the diagnosis. Most of the FNSs of patients with normal facial nerve function could be dissected off the nerve trunk without losing FN function. FNS patients with preoperatively abnormal FN function should be managed conservatively or undergo reconstruction with nerve graft after tumour resection.

EMMPRIN silencing inhibits proliferation and perineural invasion of human salivary adenoid cystic carcinoma cells in vitro and in vivo

Salivary adenoid cystic carcinoma (SACC) is a frequent subtype of salivary gland malignancy, and it has an important biological behavior for perineural invasion (PNI). Extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that is involved in the invasive property of many malignancies by stimulating matrix metalloproteinase (MMP) expression. The present study was designed to investigate the role and possible mechanism of EMMPRIN in the PNI of SACC using RNA interference (RNAi) technology. We found that silencing of EMMPRIN expression in the human SACC cell line (SACC-83) suppressed the cell proliferation, adhesion, MMP-2 and MMP-9 secretion, and PNI activity in vitro. EMMPRIN silencing also inhibited the tumor growth and Ki-67 labeled proliferation index in vivo. Using tumor PNI models in nude mice, EMMPRIN silencing inhibited the infiltration, swelling and functional loss of the affected sciatic nerves, as well as the expression of MMP-2 and MMP-9. These results demonstrate that EMMPRIN participates in the PNI of SACC cells by mediating the expression of MMP-2 and MMP-9. Our findings suggest that EMMPRIN is a potential target for anti-PNI treatment in SACC.

BDNF mediated TrkB activation contributes to the EMT progression and the poor prognosis in human salivary adenoid cystic carcinoma.

BACKGROUND The aim of the present study was to investigate whether the expression of Brain-Derived Neurotrophic Factor (BDNF) and its receptor Tropomyosin-related kinase B (TrkB) is correlated with the clinical progression of salivary adenoid cystic carcinoma (SACC) and whether the BDNF/TrkB axis is associated with the induction of epithelial-mesenchymal transition (EMT) in SACC cells. METHOD The expression of BDNF, TrkB, and E-cadherin (an EMT biomarker) in 76 primary SACC specimens and 20 normal salivary gland tissues was analyzed by immunohistochemistry. Additionally, the expression of BDNF, TrkB, and E-cadherin in SACC cell lines (SACC-83 and SACC-LM) was analyzed by RT-PCR and Western blotting. The biological role of the BDNF/TrkB axis in the EMT progression of SACC was evaluated after treatment with increased levels of BDNF and by inhibiting TrkB activity in SACC-83 cell line. The progression of SACC cells through EMT was assessed by RT-PCR, Western blotting, photography, migration and invasion assays. RESULTS Elevated expression of TrkB (92.1%) and BDNF (89.5%), and downregulated expression of E-cadherin (47.4%) was found in SACC specimens, which was significantly correlated with the invasion and metastasis in SACC (P<0.05). The high expression of TrkB and the low expression of E-cadherin was significantly correlated with the poor prognosis of SACC patients (P<0.05). The expression of TrkB was inversely correlated with the expression of E-cadherin in both SACC cases and cell lines (P<0.05). Increasing BDNF levels after treatment with exogenous recombinant human BDNF (rhBDNF) at 100 ng/ml significantly promoted the activation of TrKB and the progression of EMT in SACC cells. While obstruction of TrkB by its inhibitor, k252a (100 nM), significantly inhibited the EMT progression of SACC cells. CONCLUSIONS These results suggest that BDNF-mediated TrkB activation contributes to the EMT progression and the poor prognosis in SACC. The present study demonstrated that the BDNF/TrkB axis promotes the migration and invasion of SACC cells via EMT in vitro. Targeting the inactivation of the BDNF/TrkB axis may be a potential strategy for the treatment of SACC.

Local injection of nerve growth factor via a hydrogel enhances bone formation during mandibular distraction osteogenesis

OBJECTIVE The objective of this study was to evaluate the effects of the injectable NGF-carrying collagen/nano-hydroxyapatite/alginate hydrogel on the bone formation in a rabbit mandibular distraction osteogenesis model. STUDY DESIGN Thirty-five New Zealand white rabbits underwent bilateral madibular distraction osteogenesis at a rate of 0.75 mm/12 h for 6 days. The rabbits were divided into 4 groups: group 1 received injections of collagen/nano-hydroxyapatite/alginate hydrogel containing hNGFβ; groups 2, 3, and 4 received injections of hNGFβ, Col/nHA/Alg hydrogel, and saline, respectively. The injections were performed on both sides of the mandible at the end of the lengthening phase. All the animals were killed at a consolidation time of 14 days. RESULTS No difference in regenerate bone dimensions was observed among the 4 groups. Bone mineral density, the maximum load, and the bone volume/total volume of the new bone in the distraction gap in group 1 was significantly greater (P < .05) than in the other 3 groups. CONCLUSIONS Application of the Col/nHA/Alg hydrogel as an NGF delivery during the consolidation phase of distraction osteogenesis increased regeneration and new bone formation.

EMMPRIN contributes to the in vitro invasion of human salivary adenoid cystic carcinoma cells

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that is involved in tumor invasion by stimulating matrix metalloproteinase (MMP) expression. Our previous immunohistochemical study found that the expression of EMMPRIN in salivary adenoid cystic carcinoma (SACC) was positively correlated with tumor perineural and perivascular invasion. The present study was designed to further investigate the role of EMMPRIN in the invasion of SACC. Western blot results showed that EMMPRIN was upregulated in the highly metastatic SACC cell line SACC-LM, compared to SACC-83, a SACC cell line with low metastatic ability. Blocking of EMMPRIN by its antibody significantly decreased the adhesion, secretion of MMP-2 and MMP-9, and invasion activity of SACC-LM cells in vitro (P<0.01). Co-cultures of SACC-LM cells with fibroblasts significantly produced elevated levels of MMP-2 and MMP-9, and promoted the in vitro invasion activity of SACC-LM cells, compared with cultures of SACC-LM cells alone (P<0.01). These results indicate that EMMPRIN may play an important role in the invasion of SACC by stimulating the expression of MMP-2 and MMP-9 in tumor and stromal cells.

Notch1 signaling pathway participates in cancer invasion by regulating MMPs in lingual squamous cell carcinoma

Some studies show the Notch signaling pathway may participate in carcinoma invasion and metastasis. However, the mechanisms by which Notch1 mediates cell invasion and migration, especially in lingual squamous cell carcinoma, are not yet known. In the current study, we demonstrated for the first time the anti-invasion and anti-metastasis effect of down-regulation of Notch1 in lingual squamous cell carcinoma. Down-regulation of Notch1 could be an effective approach for inhibition of the expression of matrix metalloproteinase (MMP)-2 and MMP-9 resulting in the inhibition of invasion and metastasis, which could be useful for devising novel preventive and therapeutic strategies for lingual squamous cell carcinoma.

Application of nerve growth factor by gel increases formation of bone in mandibular distraction osteogenesis in rabbits.

The long period of bony consolidation is a concern in mandibular distraction osteogenesis (DO). We have previously shown that repeated local injections of human nerve growth factor beta (NGFβ) can appreciably improve bony consolidation in a rabbit model of DO. The present study was designed to test the effect of a single injection of human NGFβ delivered by collagen/nano-hydroxyapatite/kappa-carrageenan gels to sites of new bony formation in DO. Rabbits underwent mandibular DO at a rate of 0.75 mm/12h for 6 days. At the end of the distraction period, the following injections were given percutaneously into the callus (n=6 in each of the four groups): human NGFβ in the gel; human NGFβ in saline; the gels alone; and saline alone. Fourteen days after the end of distraction, mechanical testing, histological and histomorphometric variables of the new bone were evaluated. Histologically, the NGFβ group had more advanced consolidation than the other three groups. Both maximal load and bone volume/total volume in this group were significantly higher than in the other three (P<0.05). In conclusion, the delivery of human NGFβ in the gels results in better acceleration of new bone formation than when it is given in saline, and may be a possible way to shorten the duration of craniofacial DO.

Effects of locally applied nerve growth factor to the inferior alveolar nerve histology in a rabbit model of mandibular distraction osteogenesis.

Distraction osteogenesis (DO) is widely used in deformities and defects of the craniofacial bone. Accelerating inferior alveolar nerve (IAN) recovery would aid the process. Nerve growth factor (NGF) plays a vital role in peripheral nerve regeneration. In this study, the ability of locally applied human NGF beta (hNGFbeta) to enhance the morphological recovery of the IAN in a rabbit model of mandibular DO was studied. Rabbits underwent bilateral DO with a rate of 0.5mm per 12h. Two doses of 40 microg hNGFbeta in buffer were injected into callus at the beginning the of consolidation time. The contralateral side received injections of placebo. Rabbits were killed at 14 and 28 days. IAN specimens were subjected to histological and histomorphometric analysis. In both 14 and 28 days consolidation experiments, nerve histological analysis showed less degeneration and more regeneration in nerve fibers on the hNGFbeta treated side than the control side. Histomorphometric analysis showed that the myelinated fiber density on the hNGFbeta treated side was significantly higher than on the control side (p<0.01). The data indicate that locally applied hNGFbeta can accelerate the morphological recovery of the IAN and may play a role in reducing nerve injury in mandibular DO clinically.