• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.2
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• pp.95-110
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• 2006

The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.5
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• pp.272-281
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• 2003

Nontraditional or alternative medicine is becoming an increasingly attractive approach for the treatment of various inflammatory disorders and cancers. Curcumin is the major constitute of turmoric powder extracted from the rhizomes of the plant Curcuma longa. Resveratrol is a phytoalexin present in grapes and a variety of medicinal plants. In this report, We investigated the effect of curcumin and resveratrol on regulatory protein of cell cycle, induction of apoptosis and MMP activity. Treatment with 75 M curcumin for 24 hrs produced morphological changing in HN-4 cells. Curcumin and resveratrol inhibited the cellular growth in HN-4 cells. Inhibition of cell growth was associated with down-regulation of cell cycle regulatory proteins. Curcumin-induced caspase-3 activation and Bax degradation were dose-dependent with a maximal effect at a concentration of 100 M. The elevated caspase-3 activity in curcumin treated HN-4 cells are correlated with down-regulation of survivin and cIAP1, but not cIAP2. Curcumin induced a dose-dependent increase of cytochrome c in the cytosol. Curcumin induced-apoptosis was mediated through the release of cytochrome c. In addition, curcumin-induced apoptosis was caused by the generation of reactive oxygen species, which was prevented by antioxidant N-acetyl-cysteine (NAC). Cotreatment with NAC markedly prevented cytochrome c release, Bax cleavage and cell death. Also resveratrol-induced apoptosis was preceded by down-regulation of the anti-apoptotic Bcl-2, cIAP1, and caspase-3 activity. However, resveratrol-induced apoptosis was not prevented by antioxidant NAC. In addition, HN-4 cells release basal levels of MMP2 when cultured in serum-free medium. Treatment of the cells with various concentrations of PMA for 24 hr induced the expression and secretion of latent MMP9 as determined by gelatin zymography. HN-4 cells were treated with various concentrations of curcumin and resveratrol in the presence of 75 nM PMA, and MMP2 and 9 activities were inhibited by curcumin and resveratrol. These findings have implications for developing curcumin-based anticancer and anti-inflammation therapies.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.6
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• pp.644-651
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• 2000

In cases of severe alveolar bony resorption in the edentulous posterior maxillae, implant placement is limited anatomically due to maxillary sinus. If the ridge is atrophic, the various bone grafting methods are required for the ridge augmentation. But the result of the onlay grafting procedure is not always promising. On the posterior maxilla, maxillary sinus mucosa lifting and bone grafting into the sinus floor, subantral augmentation(SA) technique are recommended. Various SA procedures have been developed for implant installation. We perfer to simultaneous block bone graft and implant installation through the residual alveolar ridge into the grafted block bone to fix the grafted bone and to gain the primary stability of the installed fixture. When a sagittal skeletal discrepancy in present due to the severe alveolar bony resorption of the maxilla, the advancement of the maxilla by Le Fort I osteotomy simultaneously with installation of implant fixtures combined with sinus lifting and interpositional bone graft procedure can be indicated. We applied various SA techniques for implant installtion to the 46 edentulous posterior maxillae, and total 154 implants were installed at our department from 1992 to 1999. Various SA techniques were classified in detail and the indications of each techniques were discussed. The changes of residual bony height following SA procedure were studied. The results were as follows. 1. The SA procedure combined with bone graft and simultaneous fixture installation were performed in 41 cases, 126 fixtures were installed and 5 fixtures were removed out of them. Le Fort I osteotomy procedure combined with sinus lifting and interpositional bone graft simultaneous with fixture installation were performed in 5 cases. Total 28 fixtures were installed and 2 fixtures were removed so far. 2. Autogenous block bone graft into sinus floor were performed in 35 cases, autogenous particulated marrow cancellous bone(PMCB) graft in 9 cases, and demineralized human bone powder in 2 cases. The donor site for bone graft were anterior iliac bone in 39 cases, posterior iliac bone in 3 cases and mandibular symphysis in 1 case and mandibular ramus in 1 case. 3. In 9 cases with which SA procedure had been performed with the block bone graft, the change of pre- and postoperative residual bony height were measured using MPR(multiplanar reformatted)-CT. The mean residual bony height was 8.0mm preoperatively, 20.2mm at 6 months following up operation and we gained average 12.2mm alveolar bony height. So, we can recommend this one-stage subantral augmentation and fixture installation technique as a time conserving, safe and useful method for compromised posterior edentulous maxilla.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.22 no.2
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• pp.164-173
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• 2000

The p16 protein is a cyclin dependent kinase inhibitor that inhibits cell cycle progression from $G_1$ phase to S phase in cell cycle. Many p16 gene mutations have been noted in many cancer-cell lines and in some primary cancers, and alterations of p16 gene function by DNA methylation have been noticed in various kinds of cancer tissues and cell-lines. There have been a large body of literature has accumulated indicating that abnormal patterns of DNA methylation (both hypomethylation and hypermethylation) occur in a wide variety of human neoplasma and that these aberrations of DNA methylation may play an important epigenetic role in the development and progression of neoplasia. DNA methylation is a part of the inheritable epigenetic system that influences expression or silencing of genes necessary for normal differentiation and proliferation. Gene activity may be silenced by methylation of up steream regulatory regions. Reactivation is associated with demethylation. Although evidence or a high incidence of p16 alterations in a variety of cell lines and primary tumors has been reported, that has been contested by other investigators. The precise mechanisms by which abnormal methylation might contribute to carcinogenesis are still not fully elucidated, but conceivably could involve the modulation of oncogene and other important regulatory gene expression, in addition to creating areas of genetic instability, thus predisposing to mutational events causing neoplasia. There have been many variable results of studies of head and neck squamous cell carcinoma(HNSCC). This investigation was studied on 13 primary HNSCC for p16 gene status by protein expression in immunohistochemistry, and DNA genetic/epigenetic analyzed to determine the incidence, the mechanisms, and the potential biological significance of its Inactivation. As methylation detection method of p16 gene, the methylation specific PCR(MSP) is sensitive and specific for methylation of any block of CpG sites in a CpG islands using bisulfite-modified DNA. The genomic DNA is modified by treatment with sodium bisulfate, which converts all unmethylated cytosines to uracil(thymidine). The primers designed for MSP were chosen for regions containing frequent cytosines (to distinguish unmodified from modified DNA), and CpG pairs near the 5' end of the primers (to provide maximal discrimination in the PCR between methylated and unmethylated DNA). The two strands of DNA are no longer complementary after bisulfite treatment, primers can be designed for either modified strand. In this study, 13 paraffin embedded block tissues were used, so the fragment of DNA to be amplified was intentionally small, to allow the assessment of methylation pattern in a limited region and to facilitate the application of this technique to samlples. In this 13 primary HNSCC tissues, there was no methylation of p16 promoter gene (detected by MSP and automatic sequencing). The p16 protein-specific immunohistochemical staining was performed on 13 paraffin embedded primary HNSCC tissue samples. Twelve cases among the 13 showed altered expression of p16 proteins (negative expression). In this study, The author suggested that low expression of p16 protein may play an important role in human HNSCC, and this study suggested that many kinds of genetic mechanisms including DNA methylation may play the role in carcinogenesis.

• Journal of Oral Medicine and Pain
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• v.36 no.1
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• pp.71-79
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• 2011

Aim: Disc displacement without reduction of the temporomandibular joint (TMJ) has been managed by mandibular manipulation to reduce the displaced disc but with a low success rate. The purpose of this study was to determine whether auriculotemporal nerve block anesthesia had an effect on the reduction of the displaced disc and to analyze the factors that influenced the result. Methods: 112 patients were diagnosed with disc displacement without reduction and treated by mandibular manipulation. Disc was recaptured in 35 patients. Among the 77 patients with whom disc recapture had failed, the auriculotemporal nerve was blocked with a local anesthetic in the 49 patients (mean $age \;{\pm}\; SD\; =\; 34.4\;{\pm}\; 15.1$; male 24, female 25) and then mandibular manipulation was performed again. Factors including age, elapsed time from the onset, and opening amount were analyzed in association with disc reduction rate with the auriculotemporal nerve block. Results: Among 49 patients who did not respond to manipulation only, manual reduction with auriculotemporal nerve block anesthesia was successful in 19 patients (38.8%). Maximum unassisted opening amount significantly increased in the 19 patients with successful recapture of the disc ($mean \;{\pm}\; SD\; =\; 46.1 \;{\pm}\; 4.5\; mm$), in contrast to the limited opening amount of the 49 patients before local anesthesia of the auriculotemporal nerve ($mean \;{\pm}\; SD\; =\; 25.7 \;{\pm}\; 6.0\; mm$). Age, elapsed time after the onset, and preoperative opening amount were not associated with the reduction rate. Conclusion: The results of this study suggest that auriculotemporal nerve block anesthesia increases the reduction rate of the disc displacement without reduction of the TMJ when combined with mandibular manipulation, and such anesthesia should be applied at the first stage of manual treatment of disc displacement without reduction.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.2
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• pp.180-186
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• 2008

Purpose: This study was performed to evaluate the effect of the implant recipient site preparation methods on primary stability of implants with the instruments of $Osstell^{TM}$ and $Periotest^{(R)}$ in the iliac bone of cadaver. Methods and materials: The 8 iliac bones in 4 cadavers and implants treated with resorbable blasting media (RBM) were used. $Periotest^{(R)}$ (Simens AG, Germany) and $Osstell^{TM}$ (Model 6 Resonance Frequency Analyser: Integration Diagnostics Ltd., Sweden) were used to measure primary stability of implants. Implants were inserted into the iliac crest of the cadaver. In control group, the recipient site was prepared according to the manufacturer's recommendation: 1.8 mm guide drill, 2.0 mm initial drill, 2.7 mm pilot drill, 2.7 mm twist drill, 3.0 mm twist drill, 3.3 mm pilot drill, 3.3 mm twist drill, and 3.3 mm countersink drill as well as tapping drill were used in order. In the group 1, implant recipient sites were prepared by sequentially drilling from 1.8 mm guide drill to 3.0 mm twist drill and then inserted implants without countersinking and tapping. In the group 2, implant recipient sites were prepared to 3.0 mm twist drill and countersink drill and then inserted implants without tapping. In the group 3, the sites were prepared to 3.0 mm twist drill and countersink drill as well as tapping drill. In the group 4, the sites were prepared to 3.3 mm twist drill. In the group 5, the sites were prepared to 3.3 mm twist drill and countersink drill. A total of 60 implants were placed (n=10). The stability was measured using $Osstell^{TM}$ and $Periotest^{(R)}$ mesiodistally and buccolingually. To compare the mean stability of each group statistically, One-way ANOVA was used and correlation of instrument were analyzed using SPSS 12.0. The results obtained were as follows; 1. The stability of group 1 measured using $Osstell^{TM}$ and $Periotest^{(R)}$ buccolingually showed the highest, and there are significant difference statistically between control group and experimental group 1,2,4 in each instruments respectively (p<0.05). 2. The stability of group 1 measured using $Osstell^{TM}$ and $Periotest^{(R)}$ mesiodistally showed the highest. There are significant difference statistically between control group and all experimental groups in $Osstell^{TM}$, and between control group and experimental group 1,2,3,4 (p<0.05). 3. There are high correlation between the measurements of $Osstell^{TM}$ and $Periotest^{(R)}$ (p<0.05). Conclusion: These results indicate that the primary stability of implant can be obtained by the recipient sites preparation with smaller diameter drill than that of implant or minimal drilling.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.2
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• pp.166-179
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• 2008

Excessive concentration of stress which is occurred in occlusion around the implant in case of the implant supported fixed partial denture has been known to be the main cause of the crestal bone destruction. Therefore, it is essential to evaluate the stress analysis on supporting tissue to get higher success rates of implant. The purpose of this study was to evaluate the effects of stress distribution and deformation in 3 different types of three-unit fixed partial denture sup-ported by two implants, using a three dimensional finite element analysis in a three dimensional model of a whole mandible. A mechanical model of an edentulous mandible was generated from 3D scan, assuming two implants were placed in the left premolars area. According to the position of pontic, the experiments groups were divided into three types. Type I had a pontic in the middle position between two implants, type II in the anterior posi-tion, and type III in the posterior position. A 100-N axial load was applied to sites such as the central fossa of anterior and posterior implant abutment, central fossa of pontic, the connector of pontic or the connector between two implants, the mandibular boundary conditions were modeled considering the real geometry of its four-masticatory muscular supporting system. The results obtained from this study were as follows; 1. The mandible deformed in a way that the condyles converged medially in all types under muscular actions. In comparison with types, the deformations in the type II and type III were greater by 2-2.5 times than in the type I regardless of the loading location. 2. The values of von Mises stresses in cortical and cancellous bone were relatively stable in all types, but slightly increased as the loading position was changed more posteriorly. 3. In comparison with type I, the values of von Mises stress in the implant increased by 73% in Type II and by 77% in Type III when the load was applied anterior and posterior respectively, but when the load was applied to the middle, the values were similar in all types. 4. When the load was applied to the centric fossa of pontic, the values of von Mises stress were nearly $30{\sim}35%$ higher in the type III than type I or II in the cortical and cancellous bone. Also, in the implant, the values of von Mises stress of the type II or III were $160{\sim}170%$ higher than in the type I. 5. When the load was applied to the centric fossa of implant abutment, the values of von Mises stress in the cortical and cancellous bone were relatively $20{\sim}25%$ higher in the type III than in the other types, but in the implant they were 40-45% higher in the type I or II than in the type III. According to the results of this study, musculature modeling is important to the finite element analysis for stress distribution and deformation as the muscular action causes stress concentration. And the type I model is the most stable from a view of biomechanics. Type II is also a clinically accept-able design when the implant is stiff sufficiently and mandibular deformation is considered. Considering the high values of von Mises stress in the cortical bone, type III is not thought as an useful design.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.43 no.4
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• pp.221-228
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• 2017

Objectives: The purpose of this study was to establish normative data for healthy Korean adults by measuring the maximal strength and endurance scores of the tongue, lip, and cheek, and to examine correlations between these measurements. Materials and Methods: This study included 120 subjects that were divided into three groups according to age: young (20-39 years), middle-aged (40-59 years), and older (over 60 years); and by gender. Measurements were taken using the Iowa Oral Performance Instrument (IOPI). Results: The mean maximal tongue strengths were as follows: young men ($46.7{\pm}10.2kPa$) and women ($32.1{\pm}7.9kPa$), middle-aged men ($40.9{\pm}9.3kPa$) and women ($36.9{\pm}8.6kPa$), and older men ($35.2{\pm}9.0kPa$) and women ($34.5{\pm}6.9kPa$). The mean tongue endurance scores were: young men ($28.8{\pm}12.6$ seconds) and women ($20.8{\pm}13.5$ seconds), middle-aged men ($17.0{\pm}8.5$ seconds) and women ($15.3{\pm}5.2$ seconds), and older men ($15.8{\pm}6.7$ seconds) and women ($17.9{\pm}8.1$ seconds). The mean maximal lip strengths were: young men ($11.6{\pm}3.0kPa$) and women ($11.4{\pm}3.8kPa$), middle-aged men ($11.4{\pm}4.2kPa$) and women ($11.1{\pm}5.1kPa$), and older men ($14.5{\pm}3.9kPa$) and women ($11.7{\pm}2.6kPa$). The mean lip endurance scores were: young men ($41.1{\pm}23.9$ seconds) and women ($22.4{\pm}21.7$ seconds), middle-aged men ($24.3{\pm}10.3$ seconds) and women ($30.5{\pm}13.4$ seconds), and older men ($24.9{\pm}11.0$ seconds) and women ($12.8{\pm}7.6$ seconds). The mean maximal cheek strengths were: young men ($24.5{\pm}4.6kPa$) and women ($20.5{\pm}4.3kPa$), middle-aged men ($25.2{\pm}6.4kPa$) and women ($21.2{\pm}5.5kPa$), and older men ($22.4{\pm}5.3kPa$) and women ($18.0{\pm}4.8kPa$). The mean cheek endurance scores were: young men ($47.8{\pm}24.4$ seconds) and women ($43.9{\pm}25.0$ seconds), middle-aged men ($27.3{\pm}11.3$ seconds) and women ($20.0{\pm}14.6$ seconds), and older men ($21.7{\pm}14.5$ seconds) and women ($17.2{\pm}11.4$ seconds). Conclusion: The data collected in this study will provide an important database of standardized measurements for maximal strength and endurance scores of the tongue, lip and cheek in healthy, normal Koreans.

• Restorative Dentistry and Endodontics
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• v.35 no.3
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• pp.188-197
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• 2010

The purpose of this study was to compare radiopacity and radiographic discriminability of various FRC-Posts. Six FRC-Posts were investigated ; 1) FRC Postec Plus (Ivoclar Vivadent AG, Schaan, Liechtenstein), 2) Snowlight (Carbotech, Lewis center, OH, USA), 3) Dentin Post (Komet Brasseler, Lamgo, Germany), 4) Rely-X Fiber Post (3M ESPE, St.paul, MN, USA), 5) D.T.-Light Post (BISCO, Schaumburg, IL,USA), 6) Luxapost (DMG, Hamburg, Germany) The radiographs of each post with a reference 1 mm / 2 mm aluminum step-wedge was taken using digital sensor. The optical density were calculated by gray value of $10{\times}10$ pixel and compared in mm Al equivalent at five points. Six maxillary incisors of similar radiopacity were used. Radiographs of posts in Mx. incisors of lingual side of dry mandible were taken. We showed radiographs and asked the questionnaire to 3 radiologists, 3 endodontists, 3 general practitioners. The questionnaire was comprised of choices of the highest, lowest radiopaque individual post and the choices of best discriminable post at apical, coronal area. The following results were obtained. 1. Each post system showed various radiopacity. 2. There was change of discriminability between each post and simulated specimens regardless of examiner. Although each post showed various radiopacity, the difference of radiopacity did not affect on discriminability.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.5
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• pp.385-396
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• 2001

The purpose of this experiment was to examine the histological changes and the pattern of expression of proliferating cell nuclear antigen(PCNA) and type I collagen in the elongated bone affected by osteodistraction of the mandibular body in an adult canine model. Seven adult male mongrel dogs weighing over 20kg were used for this experiment. The author excluded 3 animals because they died before the planned time of sacrifice. The custom-made linear extraoral device and 4 bicortical fixation screws 2.3mm in diameter, 50mm in total length, 15mm in screw length were used in each animal. The distal part of the distractor produced a 0.75mm gap between proximal and distal bony segments every $360^{\circ}$ turn of the rotation rod of the device. The mandibular body of the right side from each animal was experimental side and the left side was left intact and served as control. At the experimental side, the mandibular body was osteotomized. After 5-day latency period, the segments were distracted with a rate of 1.1mm/day and a rhythm of two/day for ensuing 7 days. The animals were sacrificed at the 4th. 17th, and 32th day after the end of the distraction. The bony specimens were decalcified, embedded in paraffin, sectioned $5{\mu}m$ thick and stained with Masson trichrome and examined under the light microscope. The immunohistochemical examinations using anti-PCNA antibody and anti-type-I collagen antibody were performed to examine the pattern of the expression of PCNA and type I collagen, respectively. Results : 1. The mean increment of the distance between the proximal and distal screw-holding parts of the distractor was 6.8mm. The average elongation of the mandible in the experimental side was 5.3mm. The loss of elongation was 1.5mm in average. 2. New bone was already observed at the 4th. day after the end of distraction. But, bony union was not completed in the distraction gap at the 32th. day after the end of distraction by radiographic and microscopic examinations. 3. The expression rate of PCNA positive cells in the distraction gap had a tendency of decrease from 35.1-68.8% initially, to 49.1%, and finally to 17.6-27.2%. But at the final period, the tissue of the elongated gap still had the ability of cell proliferation. On the other hand, the expression of PCNA positive cells in the control side were negligible through the experimental period. 4. PCNA positive cells were observed primarily both at the central fibrous zone and at the region of just adjacent to CFZ which initiated new bone formation. 5. The expression pattern of the type I collagen was not zone-specific. They were observed diffusely throughout the elongation gap. 6. The predominant mechanism of new bone formation in the distraction gap was intramembranous. But, some of the regenerated bone was formed by endochondral ossification.