Soung Min Kim

Metastatic leiomyosarcoma in the oral cavity: Case report with protein expression profiles

Leiomyosarcoma (LMS) is a relatively uncommon malignant tumour derived from smooth muscle cells that rapidly metastasizes to distant regions. It rarely reaches oral tissues in which smooth muscle tissues are absent. We report the case of a 56-year-old woman who presented with LMS in the maxilla that had metastasized from a primary tumour in her uterus, received a total hysterectomy with bilateral salpingo-oophorectomy 9 months earlier. To reveal the poor prognosis of metastatic LMS, a total of 26 antibodies against different factors related to the proliferation, apoptosis, necrosis, and angiogenesis were simultaneously applied on the immunohistochemistry and immuno-blot detection in order to screen for expression n of different proteins in the metastatic LMS. Compared with the immunoreactions of primary uterine LMS, the different antibodies for cellular proliferation, i.e., proliferating cell nuclear antigen (PCNA), multiple primary neoplasm-2 (MPN-2), Max, p21, CDK4, p53, Rb-1, Bad, Bcl-2, epidermal growth factor receptor (EGF-R), hepatocyte growth factor (HGF), C-erbb2, Maspin, and DMBT-1, and those for angiogenesis, i.e., vWF, CD31, and Angiogenin, were more intensely expressed, while Bax, p16, Wnt-1, E-cadherin, and APC were relatively weakly expressed. In particular, beta-catenin was densely localized to the nuclei of tumour cells. These data suggest that rapid proliferation of the tumour cells is related to over-expression of different oncogenes, and that the infiltrative growth and early distant metastasis of these tumour cells are related to over-expression of angiogenesis factors. A total of seven cases of metastatic LMS to the oral cavity that had been published in the English literature were reviewed, and the reason for the poor prognosis in the metastatic LMS is suggested in this case report.

Synergistic effects of dimethyloxalylglycine and butyrate incorporated into α-calcium sulfate on bone regeneration.

Osteogenesis is closely related to angiogenesis, and the combined delivery of angiogenic and osteogenic factors has been suggested to enhance bone regeneration. Small molecules have been explored as alternatives to growth factors for tissue regeneration applications. In this study, we examined the effects of the combined application of angiogenic and osteogenic small molecules on bone regeneration using a prolyl hydroxylase, dimethyloxalylglycine (DMOG), and a histone deacetylase inhibitor, butyrate. In a critical size bone defect model in rats, DMOG and butyrate, which were incorporated into α calcium sulfate (αCS), resulted in synergistic enhancements in bone and blood vessel formation, eventually leading to bone healing, as confirmed by micro-CT and histological analyses. In MC4 pre-osteoblast cultures, DMOG and butyrate enhanced the pro-angiogenic responses and osteoblast differentiation, respectively, which were evaluated based on the levels of hypoxia inducible factor (HIF)-1α protein and the expression of pro-angiogenic molecules (VEGF, home oxidase-1, glucose transporter-1) and by alkaline phosphatase (ALP) activity and the expression of osteoblast phenotype marker molecules (ALP, α1(I)col, osteocalcin, and bone sialoprotein). DMOG combined with butyrate synergistically improved osteoblast differentiation and pro-angiogenic responses, the levels of which were drastically increased in the cultures on αCS disks. Furthermore, it was demonstrated that αCS increased the level of HIF-1α and as a consequence VEGF expression, and supported osteoblast differentiation through the release of calcium ions from the αCS. Altogether, the results of this study provide evidence that a combination treatment with the small molecules DMOG and butyrate can expedite the process of bone regeneration and that αCS can be an efficient delivery vehicle for the small molecules for bone regeneration.

New approach for the treatment of osteoradionecrosis with pentoxifylline and tocopherol

Osteoradionecrosis (ORN) of the jaw is a significant complication of radiotherapy for oral cavity cancer. In addition to antibiotic medication, treatment options such as hyperbaric oxygen therapy, surgical approaches, and combined therapy with pentoxifylline and tocopherol have been recently introduced.In this review article, we will discuss the definition and classifications of osteoradionecrosis, its etiology and pathophysiology, previous treatment options, oral and maxillofacial complications of radiotherapy, basic information on pentoxifylline and tocopherol, recent reports of pentoxifylline and tocopherol combined therapy, and, finally, ORN-induced animal models and future approaches.

Human papilloma virus in oral cancer

Cervical cancer is the second most prevalent cancer among women, and it arises from cells that originate in the cervix uteri. Among several causes of cervical malignancies, infection with some types of human papilloma virus (HPV) is well known to be the greatest cervical cancer risk factor. Over 150 subtypes of HPV have been identified; more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region and oral cavity. The recently introduced vaccine for HPV infection is effective against certain subtypes of HPV that are associated with cervical cancer, genital warts, and some less common cancers, including oropharyngeal cancer. Two HPV vaccines, quadrivalent and bivalent types that use virus-like particles (VLPs), are currently used in the medical commercial market. While the value of HPV vaccination for oral cancer prevention is still controversial, some evidence supports the possibility that HPV vaccination may be effective in reducing the incidence of oral cancer. This paper reviews HPV-related pathogenesis in cancer, covering HPV structure and classification, trends in worldwide applications of HPV vaccines, effectiveness and complications of HPV vaccination, and the relationship of HPV with oral cancer prevalence.

Osteogenetic changes in elongated styloid processes of Eagle syndrome patients

Abnormal elongation of the styloid process, or Eagle syndrome, can be painful, and is associated with differential diagnoses including cranio-facial malformations and vasculo-neurological disturbances. The precise molecular mechanism leading to styloid process elongation is unknown. In this study, elongated styloid processes with periosteal fibrous ligament tissue were obtained from three patients with Eagle syndrome and examined by immunohistochemical methods using different antisera. In all cases, marked bony deposition was found at the apex of the styloid process. The osteogenetic proteins, such as osteonectin, osteocalcin, BMP-2, BMP-4, and RANKL were strongly positive by immunohistochemistry in both the ligament fibers and the periosteal membrane attached to the styloid process apex. Staining for protective proteins, HO-1, HSP-70, and HSP-90 was also positive. These results suggest that styloid process elongation is related to increased expression of osteogenetic and protective proteins. Therefore, we propose that Eagle syndrome results from a protective response to increased tensile stress in the ligament attached to the styloid process, which could also signal osteogenetic protein expression in the periosteal fibrous tissue.

Tbx22 expressions during palatal development in fetuses with glucocorticoid-/alcohol-induced C57BL/6N cleft palates.

T-box transcription factor 22 (Tbx22) belongs to the T-box family of transcription factors and was originally found using an in silico approach to identify new genes in the human Xq12-Xq21 region. Mutations in Tbx22 have been reported in families with X-linked cleft palate and ankyloglossia, but the underlying pathogenetic mechanism remains unknown. The aim of this study was to evaluate the expression of Tbx22 messenger RNA (mRNA) during palatogenesis in glucocorticoid-/alcohol-induced cleft palate in a C57BL/6N mouse model. Palatal development was monitored by histomorphologic and immunohistochemical studies and by in situ hybridization. Thirty pregnant C57BL/6N mice at 8 weeks of age, weighing 20 to 25 g, were used in this study. In the experimental group, 12 mice were exposed to alcohol for 7 days before mating, and 12 mice in the control group were not exposed. Six mice in a sham group were exposed to neither alcohol nor glucocorticoids. A total of 18 fetuses with induced cleft palates each from 102 fetuses in the experimental group, 109 in the control group, and 58 in the sham group were used. In both the experimental and the control groups, glucocorticoids were injected subcutaneously on gestational days (GD) 9.5, 10.5, and 11.5, and each mouse was killed on GDs 10.5 to 15.5. Histomorphologic findings were studied using hematoxylin and eosin staining, and antibodies against proliferation cell nuclear antigen, matrix metallopeptidase 9, zinc finger protein 422 (Krox25) heat shock protein 70, and Tbx22 were used in immunohistochemical analysis. Mouse Tbx22 mRNA was identified, and its expression was analyzed during embryogenesis by polymerase chain reaction and in situ hybridization. Coronal sections of the cleft maxilla of the embryos with induced cleft palates had a gap between the palatal shelves, where 2 palatal shelves had fused as in normal development but failed to meet and fuse to each other. By in situ hybridization, Tbx22 mRNA was found to be expressed in distinct areas of the head, such as the mesenchyme of the inferior nasal septum, the posterior palatal shelf before fusion, and the attachment of the tongue during normal development of the palate and maxilla from GD 11.5. Localization in the tongue frenum correlated with the ankyloglossia phenotype in the induced cleft palate animal model.

Differential protein expression in the secretory fluids of maxillary sinusitis and maxillary retention cyst.

Both maxillary sinusitis (MS) and maxillary retention cyst (MRC) involve the maxillary sinus and show similar clinical features. Clinically, differentiating between MS and MRC is sometimes difficult in asymptomatic patients, despite their quite different pathogenic behaviors. To identify differential protein expressions in the secretory fluids of MS and MRC, 25 cases of asymptomatic MS and 15 cases of asymptomatic MRC were examined pathologically in this study. All patients underwent routine endoscopic sinus surgery or modified Caldwell-Luc procedure and the sinus mucosal specimens obtained during these procedures with the approval of the Institutional Review Board. Their secretory fluids were analyzed via immunoprecipitation-based high-performance liquid chromatography (IP-HPLC) using 25 types of antiserum, including inflammatory cytokines, antimicrobial proteins, and mucosal protective proteins. In the histological examinations, MS and MRC showed similar features in the secretory columnar epithelial lining and thick submucosal connective tissue, both of which contained few inflammatory cells infiltrates. The IP-HPLC analysis revealed that TNFα, IL-1, -8, MMP-3, -10, α1-antitrypsin, cathepsin C, lysozyme, lactoferrin, β-defensin-1, -3, LL-37, mucocidin, and mucin-1 were more intensely expressed in MS than in MRC; whereas IgA, cystatin A, and proline-rich proteins were more strongly expressed in MRC than in MS. These data indicate that the secretory fluid of MS is indicative of a more robust inflammatory reaction to certain bacteria compared to that of MRC, while the secretory fluid of MRC contains more abundant mucosal protective proteins compared to that of MS. Taken together, the IP-HPLC analysis of MS and MRC secretory fluid revealed that MRC showed a weaker inflammatory reaction but a stronger mucosal protective function than MS.

Cellulose membrane as a biomaterial: from hydrolysis to depolymerization with electron beam

The cellulose membrane (CM) is a major component of plant cell walls and is both a chemically and mechanically stable synthetic polymer with many applications for use in tissue engineering. However, due to its dissolution difficulty, there are no known physiologically relevant or pharmaceutically clinical applications for this polymer. Thus, research is underway on controlled and adjusted forms of cellulose depolymerization.To advance the study of applying CM for tissue engineering, we have suggested new possibilities for electron beam (E-beam) treatment of CM. Treatment of CM with an E-beam can modify physical, chemical, molecular and biological properties, so it can be studied continuously to improve its usefulness and to enhance value.We review clinical applications of CM, cellulose binding domains, cellulose crosslinking proteins, conventional hydrolysis of cellulose, and depolymerization with radiation and focus our experiences with depolymerization of E-beam irradiated CM in this article.

Analysis of Microvascular Free Flap Failure Focusing on the Microscopic Findings of the Anastomosed Vessels.

AbstractMicrovascular flap reconstruction is known as successful technique, although vascular thrombosis can cause free flap failure. To analyze the histologic characteristics and causes of free flap failure, this clinical study examined failed free flaps, including the microanastomosed sites.This study included a total of 5 failed flaps, including 3 radial forearm free flaps, 1 latissimus dorsi free flap, and 1 fibular free flap, all performed with microvascular reconstruction surgery from 2009 to 2011 at Seoul National University Dental Hospital. At the resection surgeries of the failed nonviable flaps, histologic specimens including the microanastomosed vessels were acquired. For light microscope observation, the slides were stained with hematoxylin and eosin (HE), and also with Masson trichrome. Selected portions of graft tissue were also observed under transmission electron microscope (TEM).It was found that the cause of flap failure was the occlusion of vessels because of thrombi formation. During the microanastomosis, damage to the vessel endothelium occurred, followed by intimal hyperplasia and medial necrosis at the anastomosed site. In the TEM findings, some smooth muscle cells beneath endothelium were atrophied and degenerated. The formation of thrombi and the degeneration of the smooth muscle cells were coincident with vascular dysfunction of graft vessel.The damaged endothelium and the exposed connective tissue elements might initiate the extrinsic pathway of thrombosis at the microanastomotic site. Therefore, it is suggested that accurate surgical planning, adequate postoperative monitoring, and skillful technique for minimizing vascular injury are required for successful microvascular transfer.

Bizarre parosteal osteochondromatous proliferation in the lingual area of the mandibular body versus osteochondroma at the mandibular condyle.

BackgroundBizarre parosteal osteochondromatous proliferation (BPOP) is benign and usually occurs in the small tubular bones of the hands and feet, but it is extremely rare in the oral and maxillofacial region.MethodsThe present study compares a case of BPOP occurring in the lingual area of the right mandibular body with a representative case of osteochondroma occurring in the left mandibular condyle using immunohistochemical methods.ResultsBPOP showed no continuity to the cortical bone of the mandible on X-ray and was histologically composed of immature cartilage and bone tissues, whereas osteochondroma showed overgrowth of hypertrophic chondrocytes accompanied by mature bone with endochondral ossification. Although BPOP showed no features of cellular atypia or malignant transformation, it expressed more osteogenic proteins, including BMP-2, BMP-4, RUNX2, OC, AP, OPG, RANKL, CTGF, and bFGF, than osteochondroma. Furthermore, the perichondral spindle cells and marrow osteoblasts/fibroblasts of BPOP showed stronger immunoreaction of PCNA, p53, β-catenin, BCL2, pAKT, survivin, 14-3-3, CEA, EMA, pan-K, and S-100 than the tumor cells of osteochondroma.ConclusionsTherefore, it was presumed that similar to embryonal osteochondroid tissue, BPOP might be activated by osteogenic and oncogenic signaling and that this increased signaling may explain the rapid growth and high recurrence of BPOP.