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ABSTRACT: Sclerosing polycystic adenosis (SPA) is an uncommon salivary gland lesion similar to fibrocystic disease and adenosis of the mammary glands. To our knowledge, 51 cases of SPA have been reported in the literature to date. Sclerosing polycystic adenosis is well circumscribed, yet not encapsulated, and has sclerotic and irregularly defined lobules composed of abundant hyalinized collagen with ductal, acinar hyperplasia and areas of apocrine metaplasia. Focal cystic spaces within a dense fibrotic stroma are also characteristic features of this lesion. Most of the known cases occurred mainly in the parotid gland. In this article, we describe a case of SPA occurring in the parotid gland of a 47-year-old male patient.
The Journal of craniofacial surgery 09/2012; 23(5):e451-2. · 0.81 Impact Factor
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Oral Oncology 07/2012; 48(11):e39-41. · 2.86 Impact Factor
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ABSTRACT: Facial paralysis is an uncommon but significant complication of chronic otitis media (COM). Surgical eradication of the disease is the most viable way to overcome facial paralysis therefrom. In an effort to guide treatment of this rare complication, we analyzed the prognosis of facial function after surgical treatment.
A total of 3435 patients with COM, who underwent various otologic surgeries throughout a period of 20 years, were analyzed retrospectively. Forty six patients (1.33%) had facial nerve paralysis caused by COM. We analyzed prognostic factors including delay of surgery, the extent of disease, presence or absence of cholesteatoma and the type of surgery affecting surgical outcomes.
Surgical intervention had a good effect on the restoration of facial function in cases of shorter duration of onset of facial paralysis to surgery and cases of sudden onset, without cholesteatoma. No previous ear surgery and healthy bony labyrinth indicated a good postoperative prognosis.
COM causing facial paralysis is most frequently due to cholesteatoma and the presence of cholesteatoma decreased the effectiveness of surgical treatment and indicated a poor prognosis after surgery. In our experience, early surgical intervention can be crucial to recovery of facial function. To prevent recurrent cholesteatoma, which leads to local destruction of the facial nerve, complete eradication of the disease in one procedure cannot be overemphasized for the treatment of patients with COM.
Yonsei medical journal 05/2012; 53(3):642-8. · 0.77 Impact Factor
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Da-Woon Jung,
Jinmi Kim,
Zhong Min Che,
Eun-Sang Oh,
Gicheon Kim,
Soo Hyun Eom,
Sin-Hyeog Im,
Hyung-Ho Ha,
Young-Tae Chang,
Darren R Williams, Jin Kim
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ABSTRACT: Carcinoma-associated fibroblasts (CAFs) promote tumor invasion by secreting soluble factors. A tagged triazine library was screened in our novel transwell coculture model of CAF and oral squamous cell carcinoma (OSCC). We discovered compound S06, which reduced OSCC invasion by inhibiting secretion of CAF-derived proinvasive chemokines. The N-terminus of Hsp90 was found to be the cellular target of S06. Importantly, S06 did not induce hepatic toxicity, a side effect associated with well-known Hsp90 inhibitors. Moreover, S06 inhibited tumor cell migration in a zebrafish xenograft model. Our results demonstrate that Hsp90 is a novel target for stromal-based therapy to modulate proinvasive molecular crosstalk within the tumor microenvironment. Furthermore, S06 represents a new class of Hsp90 inhibitor and is an attractive candidate for anticancer drug development.
Chemistry & biology 12/2011; 18(12):1581-90. · 6.52 Impact Factor
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ABSTRACT: The invadopodia are specialized structures that degrade the extracellular matrix (ECM) and promote cell invasion and metastasis. Understanding the forms and functions of invadopodia should facilitate the proper identification of novel targets for antiinvasive therapy.
To understand the role of insulin-like growth factor-II mRNA-binding protein-3 (IMP-3) in invadopodia formation and cancer invasion, we performed IMP-3 gene silencing, invadopodia formation, ECM degradation assay, zymography, western blot, and mouse xenograft.
We demonstrate that invadopodia evidenced ECM degradation activity in oral squamous cell carcinoma (OSCC). Downregulation of IMP-3 inhibited invadopodia formation, ECM degradation, and tumor growth and invasiveness. Epidermal growth factor receptor (EGFR) signaling may perform a critical function in invadopodia formation, ECM degradation, IMP-3, and cortactin expression.
IMP-3 may be intimately correlated with cancer invasion through invadopodia in oral cancer. The overexpression of IMP-3 in oral cancer was predictive of a high correlation with cancer growth and invasion.
Head & Neck 11/2011; 34(9):1329-39. · 2.40 Impact Factor
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ABSTRACT: We present a novel gain-of-function mutation of TGF-β receptor II (TβRII) found in human oral squamous cell carcinoma (OSCC). Expression of E221V/N238I mutant TβRII enhanced TGF-β signaling. Mutation of TβRII conferred cells higher migratory and invasive capabilities and MMP-2 activity. In mouse tumor model, mutant tumors exhibited poor differentiation and E-cadherin relocalization to the cytosol. Lipid-raft-dependent endocytosis of TβRII was attenuated in mutant TβRII, suggesting that enhancement of TGF-β signaling by this mutation is due to delayed TβRII internalization. Taken together, our results show a novel gain-of-function TβRII mutation, which enhances TGF-β signaling leading to more invasive phenotypic changes in human OSCC.
Cancer letters 10/2011; 315(2):161-9. · 4.86 Impact Factor
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ABSTRACT: Buddlejasaponin IV (BS-IV), a major component of Pleurospermum kamtschaticum, exerts antiinflammatory and cytotoxic effects against cancer cells. The study investigated whether BS-IV could prevent oral carcinogenesis by inhibiting the growth of immortalized human oral keratinocytes (IHOKs). BS-IV reduced cell viability and induced cell cycle arrest at G2/M phase and apoptotic morphological changes in IHOKs. BS-IV inhibited the levels of cyclin B1, Cdc2 and Cdc25C, but enhanced Chk2 phosphorylation. The increased levels of pRb and p21 protein and the activation of p53 were also noted in BS-IV-treated IHOKs. In addition, BS-IV induced cytochrome c release from mitochondria by reducing antiapoptotic Bcl-2 levels and increasing pro-apoptotic Bax levels. BS-IV treatment resulted in the activation of caspase-9 and caspase-3. PARP cleavage was also clearly observed in the BS-IV-treated IHOKs. Furthermore, the expression of the Fas death receptor and Fas ligand was induced and procaspase-8 level was suppressed by BS-IV treatment. Taken together, BS-IV treatment inhibited the growth of IHOK cells via the induction of p53-dependent cell cycle arrest at the G2/M phase and apoptosis via both mitochondrial-dependent and death receptor-mediated pathways. Thus, BS-IV can be considered an excellent candidate for a chemopreventive agent to block the progression of HPV-induced oral carcinogenesis.
Phytotherapy Research 03/2011; 25(10):1503-10. · 2.09 Impact Factor
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ABSTRACT: Oral squamous cell carcinoma (OSCC) is caused by multiple factors, including carcinogen exposure. Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is highly expressed in various cancer cells but is rarely expressed in normal cells. We investigated whether IMP3 can be used as a prognostic biomarker for OSCC.
We performed immunohistochemistry and Western blotting to examine IMP3 expression in human tissues. We also investigated correlations among IMP3 expression, clinicopathologic factors, and overall survival.
IMP3 was overexpressed in OSCC cells. The expression was correlated with high histologic grade, lymph node metastasis, and advanced tumor and clinical stages. Univariate analysis indicated that advanced clinical stages, lymph node metastases, and IMP3 expression were predictive factors for OSCC. Multivariate analysis showed that IMP3 expression was an independent prognostic indicator for OSCC.
IMP3 expression was related to various clinicopathologic factors. IMP3 expression was an independent prognostic factor in patients with OSCC.
Head & Neck 03/2011; 33(3):368-74. · 2.40 Impact Factor
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PhD Shengjin Li MD,
JeongDan Cha PhD,
PhD Jin Kim DDS,
Ki-Yeol Kim PhD,
PhD Hyung-Jun Kim DDS,
PhD Woong Nam DDS,
PhD In-Ho Cha DDS,
Shengjin Li,
JeongDan Cha, Jin Kim,
Ki‐Yeol Kim,
Hyung‐Jun Kim,
Woong Nam,
In‐Ho Cha
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ABSTRACT: Background.Oral squamous cell carcinoma (OSCC) is caused by multiple factors, including carcinogen exposure. Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is highly expressed in various cancer cells but is rarely expressed in normal cells. We investigated whether IMP3 can be used as a prognostic biomarker for OSCC.Methods.We performed immunohistochemistry and Western blotting to examine IMP3 expression in human tissues. We also investigated correlations among IMP3 expression, clinicopathologic factors, and overall survival.Results.IMP3 was overexpressed in OSCC cells. The expression was correlated with high histologic grade, lymph node metastasis, and advanced tumor and clinical stages. Univariate analysis indicated that advanced clinical stages, lymph node metastases, and IMP3 expression were predictive factors for OSCC. Multivariate analysis showed that IMP3 expression was an independent prognostic indicator for OSCC.Conclusions.IMP3 expression was related to various clinicopathologic factors. IMP3 expression was an independent prognostic factor in patients with OSCC. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Head & Neck 02/2011; 33(3):368 - 374. · 2.40 Impact Factor
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ABSTRACT: The aim of this study was to investigate whether vitrification in the cryopreservation of periodontal ligament (PDL) cells could be useful for tooth banking.
In step 1, primary cultured human PDL cells were cryopreserved in 100% conventional cryopreservation media and 100% vitrification media (ESF40 media) in different temperatures for 2 weeks. In step 2, a series of modified vitrification formulae named T1 (75% vitrification media + 25% F-media), T2 (50% vitrification media + 50% F-media) and T3 (25% vitrification media + 75% F-media) were used to store PDL cells for 2 weeks and 4 weeks in liquid nitrogen. MTT assay was performed to examine the viability of PDL cells.
Maximum cell viability was achieved in cells stored in 100% conventional cryopreservation media at -196 (positive control group) in step 1. Compared to the positive control group, viability of the cells stored in 100% vitrification media was very low as 10% in all test conditions. In step 2, as the percentage of vitrification media decreased, the cell viability increased in cells stored for 2 weeks. In 4-week storage of cells in step 2, higher cell viability was observed in the T2 group than the other vitrification formulae while the positive control group had the highest viability. There was no statistically significant difference in the cell viability of 2-week and 4-week stored cells in the T2 group.
These observations indicate 100% vitrification media is not successful in PDL cell cryopreservation. Conventional cryopreservation media is currently the most appropriate media type for this purpose while T2 media would be interesting to test for long-term storage of PDL cells.
Journal of periodontal & implant science 06/2010; 40(3):111-8.
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ABSTRACT: Array comparative genomic hybridization (aCGH) provides a genome-wide technique for identifying chromosomal aberrations in human diseases, including cancer. Chromosomal aberrations in cancers are defined as regions that contain an increased or decreased DNA copy number, relative to normal samples. The identification of genomic regions associated with systematic aberrations provides insights into initiation and progression of cancer, and improves diagnosis, prognosis, and therapy strategies. The McNemar test can be used to detect differentially expressed genes after discretization of gene expressions in a microarray experiment for the matched dataset. In this study, we propose a method to detect significantly altered DNA regions, shifted McNemar test, which is based on the standard McNemar test and takes into account changes in copy number variations and the region size throughout the whole genome. In addition, this novel method can be used to detect genomic regions associated with the progress of oral squamous cell carcinoma (OSCC). The performance of the proposed method was evaluated based on the homogeneity within the selected regions and the classification accuracies of the selected regions. This method might be useful for identifying new candidate genes that neighbor known genes based on the whole-genomic variation because it detects significant chromosomal regions, not independent probes.
Medical & Biological Engineering 03/2010; 48(5):459-68. · 1.76 Impact Factor
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ABSTRACT: Recent studies have shown that stromal fibroblasts have a more profound influence on the initiation and progression of carcinoma than was previously appreciated. This study aimed at investigating the reciprocal relationship between cancer cells and their associated fibroblasts at both the molecular and cellular level in oral squamous cell carcinoma (OSCC). To identify key molecular regulators expressed by carcinoma-associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing cocultured OSCC cells and CAF with monoculture controls. Microarray and real-time PCR analysis identified marked upregulation of the chemokine (C-C motif) ligand 7 (CCL7) in cocultured CAF. ELISA showed an elevated level of CCL7 secretion from CAF stimulated by coculture with OSCC cells. CCL7 promoted the invasion and migration of OSCC cells, and the invasiveness was inhibited by treatment with CCL7 neutralizing antibody. OSCC cells were shown to express CCR1, CCR2 and CCR3, receptors for CCL7, by RT-PCR. In addition, treatment with anti-CCR1 or anti-CCR3 antibody inhibited CCL7-induced OSCC cell migration, implicating that CCL7 promotes cancer cell migration through CCR1 and CCR3 on OSCC cells. Cytokine antibody array analysis of the supernatant from OSCC cell culture revealed that interleukin-1alpha was an inducer of CCL7 secretion by CAF. This study confirms the reciprocal relationship of the molecular crosstalk regulating the invasion of OSCC and describes new potential targets for future therapy.
International Journal of Cancer 11/2009; 127(2):332-44. · 5.44 Impact Factor
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ABSTRACT: Array comparative genomic hybridization (aCGH) provides a technique to survey the human genome for chromosomal aberrations in disease. The identification of genomic regions with aberrations may clarify the initiation and progression of cancer, improve diagnostic and prognostic accuracy, and guide therapy. The analysis of variance (ANOVA) model is widely used to detect differentially expressed genes after accounting for common sources of variation in microarray analysis. In this study, we propose a method, shifted ANOVA, to detect significantly altered regions. This method, based on the standard ANOVA, analyzes changes in copy number variation for regions. The selected regions have the group effect only, but no effect within samples and no interactive effects. The performance of the proposed method is evaluated from the homogeneity and classification accuracies of the selected regions. Shifted ANOVA may identify new candidate genes neighboring known because it detects significantly altered chromosomal regions, rather than independent probes.
Genomics 09/2009; 94(5):317-23. · 3.02 Impact Factor
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ABSTRACT: Oral squamous cell carcinomas (OSCCs) are characterized by a marked propensity for local invasion, so the identification of agents inhibiting the onset and progression of OSCC has recently gained interest. Here, we found that curcumin inhibited cell proliferation and motility with decreased activities of matrix metalloproteinase (MMP)-2/9 and decreased mRNA expressions of urokinase-type plasminogen activator (uPA) and its receptor uPAR in the highly invasive human YD-10B OSCC cells. Western blot analysis showed that curcumin inhibited the activation of MAP kinases (especially ERK) and NF-kappaB, which are involved in the transcriptional regulation of proteolytic enzymes. In conclusion, curcumin is one of the strong phytochemicals with antimotility activity of OSCC; the inhibitory effect of curcumin on the motility of YD-10B cells could result from its potential to inhibit the activation of ERK/MAP kinase and NF-kappaB that consequently down-regulate the mRNA expressions and activities of proteolytic enzymes such as uPA and MMP-2/9.
Phytotherapy Research 09/2009; 24(4):577-82. · 2.09 Impact Factor
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ABSTRACT: Background and aim: The deregulation of transforming growth factor β (TGF-β) action and its signaling function has been a widely accepted concept in carcinogenesis. However, its dual roles, as a tumor suppressor gene and oncogene, have interfered in applying TGF-β signaling to cancer therapeutics. To evaluate its role in the carcinogenesis of oral squamous cell carcinoma (OSCC), we performed mutational analysis of the TGF-β type II receptor (TβRII). Methods: Eighteen cases of OSCC were used for mutational analysis of TβRII. Normal surgical margin, dysplastic lesion, invasive carcinoma and metastatic cancer cells into lymph node tissue were used. Exon-specific spanning primers of exon 1, 2, 3, 4, 5, 6, 7 of TβRII were used for the mutational analysis. Results: A single nucleotide polymorphism (SNP) at the codon 191 was found in 8 cases. The genetic mutations were mainly found in exon 4 through dysplastic areas, carcinoma and metastatic areas, which induced the structural change or the alteration of hydrophobicity of the amino acid. Conclusions:TβRII mutations occur frequently in exon 4 in OSCC and their functional significance should be proven.
Basic and Applied Pathology 08/2009; 2(3):82 - 88.
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ABSTRACT: Our study investigated the histogenesis and biological significance of spindle cell carcinoma (SpCC) by comparing with moderately-well-differentiated squamous cell carcinoma (SCC) cell lines. Snail mRNA expression was readily detectable in the SpCC cell line, while E-cadherin was undetectable. SpCC cells showed lower proliferative and invasive activities than two other SCC cell lines. Culturing under air-liquid interface conditions promoted squamous cell differentiation, whereas fibroblastic differentiation after submerged culture with collagen, suggesting that the microenvironment may be a regulating factor of spindle cell differentiation as well as Snail expression and spindle cell change may not always entail the invasive behavior.
Cancer letters 12/2008; 275(1):61-71. · 4.86 Impact Factor
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ABSTRACT: Carbonic anhydrase IX (CA9) is reportedly overexpressed in several types of carcinomas, but little is known about the expression pattern of CA9 in oral cavity cancer and the corresponding normal tissues. We aimed to assess the prevalence of CA9 expression and its prognostic implications in patients with oral cavity squamous cell carcinoma (SCC). Immunohistochemical staining with anti-CA9 antibody was performed in 117 oral SCC samples. Clinicopathologic factors were correlated with the results of CA9 expression. CA9 expression was restricted to tumor cells and did not appear in the corresponding normal tissue. Among 117 samples, 68 (58.1%) tumors displayed CA9 overexpression. CA9 expression was significantly associated with postoperative recurrence (P = .05) and poor overall survival (P = .02). CA9 expression was also associated with male sex, lymph node metastasis, and smoking history, but these correlations did not reach statistical significance. In conclusion, CA9 expression was a frequent and tumor-specific event in oral SCC. CA9 demonstrated significant associations with disease recurrence and poor clinical outcome and shows potential as a prognostic factor for oral SCC.
Human pathology 05/2008; 39(9):1317-22. · 3.03 Impact Factor
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ABSTRACT: Calcifying odontogenic cysts (COCs) evidence a variety of histopathological features, in addition to biological behaviors. Several systems have been proposed for the classification of COCs. However, the molecular changes underlying their development remain largely unknown. In an effort to elucidate the participation of beta-catenin gene mutation in COC development, we evaluated the genetic alterations and expression of beta-catenin in different COC subtypes with archival paraffin blocks. beta-catenin gene mutations were detected in all subtypes. Immunohistochemically, all cases of COCs evidenced cytoplasmic and nuclear beta-catenin expression. Beta-catenin gene mutations and beta-catenin overexpression have been identified as characteristics of COCs. Therefore, the constitutive activation of Tcf/Lef-dependent transcription appears to be intimately involved in their development. These findings indicate that aberrations of the Wnt signaling pathway may perform a crucial role in the development and differentiation status of the odontogenic epithelium in COCs via the deregulation of cell proliferation.
Apmis 04/2008; 116(3):206-11. · 1.99 Impact Factor
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Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics 06/2007; 103(5):636-41. · 1.50 Impact Factor
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ABSTRACT: The multifunctional G-protein-coupled metabotropic glutamate receptor (mGluR) family comprises eight subtypes, some of which participate in tumorigenesis. The purpose of this study was to evaluate mGluR5 expression in oral squamous cell carcinoma (SCC) tissues and oral cancer cell lines. We also investigated the prognostic significance of mGluR5 and its functional importance in the migration, invasion, and adhesion of oral cancer cells. We evaluated the expression of mGluR5 in samples from 131 oral SCC patients and in several oral cancer cell lines by immunohistochemistry and RT-PCR. We observed varying levels of mGluR5 in human oral SCC tissues and cancer cell lines. There was a significant association between strong mGluR5 immunoreactivity and overall survival (P=0.0109). The functional significance of the expression of mGluR5 in oral cancer cells was then investigated in HSC3 oral tongue cancer cells. An mGluR5 agonist, DHPG increased tumor cell migration, invasion, and adhesion in HSC3 cells (P<0.05). This was reversed by the mGluR5 antagonist MPEP. Our results strongly suggest that mGluR5 is a new prognostic marker and contributes to tumor cell migration and invasion in oral cancer.
Oncology Reports 02/2007; 17(1):81-7. · 1.84 Impact Factor
