Y Ueyama

Yamaguchi University, Yamaguti, Yamaguchi, Japan

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Publications (268)829.43 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In the present study, we examined the antitumor effect of paclitaxel (PTX) in combination with cetuximab in oral squamous cell carcinoma (OSCC) and the mechanism of its enhanced antitumor activity. Treatment of OSCC (HSC2, HSC3 and HSC4) cells with PTX (0.02 µg/ml) and cetuximab (1 µg/ml) combination resulted in a significant inhibition of cell growth in vitro compared to either agent alone. Moreover, it was found by Hoechst 33258 staining that DNA fragmentation markedly occurred in OSCC cells treated with PTX and cetuximab combination treatment. Furthermore, PTX and cetuximab combination treatment reduced the expression of p65 (NF-κB) protein in OSCC cells. In our in vivo experiment, HSC2 tumor-bearing nude mice were treated with PTX (20 mg/kg/day, twice/week, 3 weeks) and/or cetuximab (20 mg/kg/day, twice/week, 3 weeks). Tumor growth was significantly suppressed by PTX and cetuximab combined treatment when compared to PTX or cetuximab alone, or the untreated control. TUNEL-positive cells were upregulated in HSC2 tumors treated with PTX and cetuximab. In addition, immunohistochemical staining revealed that expression of p65 was downregulated in HSC2 tumors treated with PTX and cetuximab. Our results indicate that cetuximab may enhance the effect of PTX in OSCC through the downregulation of PTX induced p65 expression. Therefore, the combination of PTX and cetuximab might be a promising option for OSCC treatment.
    International journal of oncology. 09/2014;
  • Koji Harada, Tarannum Ferdous, Yoshiya Ueyama
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    ABSTRACT: 5-Fluorouracil (5-FU) has been used for oral squamous cell carcinoma (OSCC) treatments, and the acquisition of resistance is the major problem to successful OSCC treatment. It has been reported that the epithelial to mesenchymal transition (EMT) is associated with chemoresistance in several types of cancers. In the present study, we established 5-FU-resistant OSCC cell lines (HSC2/FU and HSC4/FU), and aimed to elucidate the mechanism(s) involved in resistance in association with its EMT characteristics. MTT assay revealed that HSC2/FU is about 14-fold more resistant compared to HSC2, and HSC4/FU is 5-fold more resistant compared to HSC4. TUNEL assay also showed a dramatically decreased number of apoptotic cells in the 5-FU-resistant OSCC cell lines compared to each parental cell after treatment with 5-FU. Moreover, the 5-FU-resistant OSCC cell lines had typical morphologic phenotypes of EMT; loss of cell-cell adhesion, increased formation of pseudopodia and spindle-shaped morphology. Western blot analysis showed downregulated E-cadherin, and upregulated N-cadherin and Twist in the 5-FU-resistant OSCC cell lines. Results of our tumor xenograft studies coincide with our in vitro study data that confirmed the 5-FU resistant nature of HSC2/FU and HSC4/FU tumors. Moreover, immunohistochemistry showed that EMT changes (downregulated E-cadherin, and upregulated Twist and N-cadherin) occurred in the 5-FU-resistant xenografted tumor cells. These results suggest that EMT has important roles in the 5-FU-resistant OSCC cells, and that these resistant cells may be considered as useful tools for understanding the mechanisms involved in 5-FU resistance in OSCC.
    International Journal of Oncology 01/2014; · 2.66 Impact Factor
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    ABSTRACT: To clarify the mechanisms of rigid and semi-rigid mandibular repositioning devices (MRDs) in obstructive sleep apnea syndrome (OSAS), seven and 13 patients received rigid and semi-rigid MRDs, respectively. Each patient underwent polysomnographic and computed tomographic examinations at the initial consultation and after symptom improvement. Three-dimensional models of the upper airway (hard palate level to epiglottic base) were reconstructed by image processing software (Mimics version 14.2) to measure airway morphology. The mean age and body mass index were 58.1 years and 24.8 kg/m2, respectively, in the rigid MRD group and 57.9 years and 23.2 kg/m2, respectively, in the semi-rigid MRD group. The apnea-hypopnea index significantly improved (P < 0.05, Wilcoxon signed-rank test) from 22.0 to 8.9 and 20.5 to 11.5 events per hour of sleep in the respective groups. The cross-sectional areas measured at the epiglottic tip (from 2.0 to 2.6 cm2) and hard palate (from 2.6 to 3.3 cm2) levels also increased in the respective groups (P < 0.05). However, airway volume, cross-sectional area measured at the uvular tip level, and anteroposterior and transverse diameters of the airway were not significantly different. In conclusion, both types of MRDs improve respiratory status, but they affect different parts of the airway.
    Journal of Cranio-Maxillofacial Surgery. 01/2014;
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    ABSTRACT: The purpose of this study was to determine the three-dimensional reproducibility of lip movement during a posed smile using a video-based motion analyzing system. In six adult volunteers (4 males and 2 females), the lip motions during a posed smile were recorded six times. Using our recently-developed motion analyzing system, range images were produced across the whole sequence during the posed smile. Virtual grids of 5 × 5 were fitted onto the surfaces, and the three-dimensional coordinates of the intersections of these grids were then computed. The magnitude of the shift of the intersections during smiling was calculated and summed in each area. Intraclass correlation coefficients (ICC), ICC (1,1) for intra-rater reliability and ICC (2,1) for inter-rater reliability were calculated. The number of repeated measurements necessary for an ICC level beyond 0.8 was determined using the formula of Spearman-Brown. The ICC (1,1) and ICC (2,1) ranged from 0.71 to 0.83 and from 0.77 to 0.99, respectively. The number of repeated measurements necessary for an ICC beyond 0.8 was 2. From the present study, both the three-dimensional intra-rater and inter-rater reliabilities during a posed smile were considered to be relatively high, and enough reliability could be expected by calculating the average of the values measured two times. However, the sample size was very small, this could not be generalized simplistically.
    Journal of cranio-maxillo-facial surgery: official publication of the European Association for Cranio-Maxillo-Facial Surgery 07/2013; · 1.25 Impact Factor
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    ABSTRACT: OBJECTIVES/HYPOTHESIS: To measure movements of the velopharynx in detail, a novel method of producing range images of the velopharynx was developed using a 3-D endoscope. The purpose of this paper is to introduce this system and to clarify its accuracy. STUDY DESIGN: The standard errors of repeated measurements, intraclass correlation coefficients (ICC), ICC(1,1) for intrarater reliability, and ICC(2,1) for interrater reliability were measured using a phantom of the nasopharynx. METHODS: An endoscopic measuring system was developed in which a pattern projection system was incorporated into a commercially available 3-D endoscope. Right and left images of the endoscope were integrated into one video file and digitized at a horizontal and vertical resolution of 640 × 480 pixels, as odd and even scanning lines, respectively. After separation of the video file into right and left images by interlace interpolation, correcting the distortion of the camera images, rectifying, and stereo-matching range images of the velopharynx were produced. The distances between two points, which were marked at an interval of 5 mm on the uvula and the pharynx of the phantom, were measured. RESULTS: The standard errors of repeated measurements were 0.02 horizontally and 0.01 vertically. The ICC(1,1) and ICC(2,1) were 0.83 and 0.94, and both correlation coefficients were considered to be "almost perfect." CONCLUSION: The present endoscopic measuring system provided relatively accurate and reliable range images of the velopharynx, and enabled quantitative analysis of movements of the velopharynx. LEVEL OF EVIDENCE: N/A. Laryngoscope, 2013.
    The Laryngoscope 06/2013; · 1.98 Impact Factor
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    ABSTRACT: Metronomic chemotherapy is based on administration of anticancer agents at low-doses at close regular intervals with no prolonged breaks, and aims to inhibit vascular endothelial cells as well as tumor cells. Recently, it was suggested that metronomic chemotherapy exerts anti-angiogenic effects by inducing thrombospondin-1 (TSP-1) and early growth response-1 (EGR-1), and antitumor effects by suppressing cancer stem cells. S-1 is a novel orally administered anticancer drug that is a combination of tegafur, 5-chloro-2, 4-dihydroxypyridine and oteracil potassium for maintaining efficacious concentrations of 5-FU and reducing the serious gastrointestinal toxicity associated with 5-FU. In the present study, we tried to determine the suitable administration method of S-1 against oral squamous cell carcinoma as a metronomic chemotherapy. We performed in vivo experiments in which tumor-bearing nude mice were used to examine the antitumor activity of S-1 (6.9 mg/kg). HSC2 tumors were treated with three different regimens, given as 4-week treatment and 2-week rest (4W-2W, 1 cycle); 2-week treatment and 1-week rest (2W-1W, 2 cycles); or alternate days treatment (1D-1D, 6 weeks). A fourth group served as control. Antitumor effects and body weight changes were compared in each group. Expression of TSP-1, EGR-1, CD31 and CD44 in HSC2 tumors was examined by immunohistochemistry. The treated groups showed higher tumor growth inhibition compared to the control group, and the relative tumor growth inhibition was not different between the treated groups. Briefly, each relative tumor growth inhibition was 32.4% (4W-2W), 39.6% (2W-1W) and 37.0% (1D-1D). During treatment periods, body weights were lower in the mice with 4W-2W or 2W-1W than 1D-1D or control. Moreover, reduction of microvessel density and CD44 expression, and induction of TSP-1 and EGR-1 expression was markedly seen in 1D-1D-treated tumors compared to 4W-2W-, 2W-1W-treated tumors or untreated control tumors by immunohistochemistry. These findings suggest that the 1D-1D regimen is more useful than the 4W-2W or 2W-1W regimen as a metronomic chemotherapy.
    International Journal of Oncology 05/2013; · 2.66 Impact Factor
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    ABSTRACT: Important strategies against cancer are based on the understanding of the mechanisms of tumor progression. To elucidate alterations regarding tumor progression, we have performed proteomic differential display analysis for the expression of intracellular proteins in the regressive murine fibrosarcoma cell clone QR-32 and the progressive malignant tumor cell clone QRsP-11, derived from QR-32, by means of combination of two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), and we have previously reported on relevant results. However, besides the protein spots which we already reported, we identified three more particular spots of interest. In the present study, two-dimensional western blot analysis demonstrated a significantly lower expression of three isoforms of nucleophosmin in progressive, compared to regressive cell clones. These results suggest that the down-regulation of the identified nucleophosmin proteins in QRsP-11 cells compared to QR-32 cells is possibly related to tumor malignant progression.
    Anticancer research 01/2013; 33(1):153-60. · 1.71 Impact Factor
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    ABSTRACT: OBJECTIVES: The purpose of this study was to evaluate the optimal upper threshold levels of a number of individuals and determine the most suitable upper threshold. METHODS: A phantom model and ten patients were used in this study. The phantom was made of acrylic resin and urethane resin and had nine pillar-shaped air spaces. The subjects were ten female patients with jaw deformities who were not affected by respiratory disease. The optimal threshold levels were determined using the "calculation of CT value disparities" (CCTD) technique, which we devised. In other words, the mean CT values along two lines (air apace and soft tissue) were calculated and the optimal threshold level was determined as the level that produced the maximum difference between the CT values measured inside and outside of the air space border. RESULTS: The optimal upper threshold levels of the nine phantom holes calculated using the CCTD technique method in the front-on standing position and side-on standing position were -434 HU and -456 HU, respectively. The optimal upper threshold level of the ten patients calculated using the CCTD technique was -472 HU. The true threshold level of each patient was defined as the optimal threshold level calculated using the CCTD technique. The mean threshold level was defined as -472 HU. The absolute differences between the volume measurements obtained with these two measures were considered. Therefore, the no error values were -460 HU and -470 HU. CONCLUSIONS: We consider that the most suitable upper threshold level for extracting the airway was from -460 HU to -470 HU.
    Dentomaxillofacial Radiology 07/2012; · 1.27 Impact Factor
  • Toyoko Harada, Koji Harada, Yoshiya Ueyama
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    ABSTRACT: In the present study, we investigated whether treatment with cepharanthine, a biscoclaurine alkaloid extracted from Stephania cepharantha improves the response to radiotherapy in the oral squamous cell carcinoma (OSCC) cell lines, HSC2, HSC3 and HSC4. We examined the potential mechanisms that may contribute to the enhanced radiation response induced by cepharanthine. Growth inhibition was observed in vitro with radiation or cepharanthine. A co-operative anti-proliferative effect was obtained when cancer cells were treated with cepharanthine followed by radiation. Cepharanthine also promoted the mitotic death of 3 cell lines by radiation. The results from DNA damage repair analysis in the cultured OSCC cells demonstrated that cepharanthine had a strong inhibitory effect on DNA double-strand break (DSB) repair after radiation. The combined treatment of cepharanthine and radiation led to an increase in the sub-G1 peak as shown by flow cytometry, and markedly induced apoptosis through the activation of caspase-3. Tumor xenograft studies demonstrated that the combination of cepharanthine and radiation caused growth inhibition and tumor regression of OSCC tumors in athymic mice; tumor volume was reduced from 765.7 to 226.3 mm3 in HSC2 cells (p<0.01), 391.6 to 43.7 mm3 in HSC3 (p<0.01), and from 572.6 to 174.2 mm3 in HSC4 cells (p<0.01). In addition, combined therapy markedly increased tumor cell apoptosis. Overall, we conclude that cepharanthine enhances tumor radioresponse by multiple mechanisms that may involve the induction of apoptosis and the inhibition of DNA DSB repair after exposure to radiation.
    International Journal of Oncology 05/2012; 41(2):565-72. · 2.66 Impact Factor
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    ABSTRACT: INTRODUCTION: Although mandibular repositioning devices were found to be very effective for treating obstructive sleep apnea (OSAS), they can cause side effects such as temporomandibular joint disorder and occlusal deviation. A semi-rigid device with a low frequency of side effects, the Silensor, (Erkodent Gmbh, Tuttlingen, Germany) was reported previously. The purpose of this study is to determine whether the Silensor is effective for treating OSAS. MATERIALS AND METHODS: Thirty-five OSAS patients (27 males and 8 females) who were treated with the Silensor were enrolled in this study. The mean age and body mass index of the patients were 52.2 years (23-72 years) and 24.5 kg/m(2) (19.3-31.6 kg/m(2)), respectively. The patients were classified into two groups based on the length of the apparatus connector: 0-2 or 3-4 mm. A polysomnography test was performed twice, at the first visit and after the improvement of subjective symptoms. These data were statistically analyzed using the Wilcoxon signed-rank test. RESULTS: The apnea-hypopnea index significantly improved in all OSAS patients, the mild to moderate OSAS patients, severe OSAS patients, 0- to 2-mm group, and the 3- to 4-mm group (91.4 %; p < 0.01, 88.9 %; p < 0.01, 100 %; p < 0.05, 86.4 %; p < 0.01, 100 %; p < 0.01, respectively). The only side effects of the Silensor were broken apparatus and damage to the buccal mucosa. DISCUSSION: The Silensor is useful for the treatment of OSAS. In particular, the Silensor is suitable for the first phase of OSAS treatment with oral appliances because the efficacy of the Silensor was equal to that of other oral appliances and had few side effects.
    Oral and Maxillofacial Surgery 05/2012;
  • Sleep And Breathing 05/2012; · 2.26 Impact Factor
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    ABSTRACT: OBJECTIVES: The purpose of this study was to explore the voice characteristics of patients with mandibular prognathism, and to investigate the effects of mandibular setback surgery on these characteristics using nonlinear dynamics and conventional acoustic analyses. MATERIALS AND METHODS: Sixteen patients (8 males and 8 females) who had skeletal 3, class III malocclusion without cleft palate, and who underwent a bilateral sagittal split ramus osteotomy (BSSRO), were enrolled. As controls, 50 healthy adults (25 males and 25 females) were enrolled. The mean first LEs (mLE1) computed for each one-second interval, and the fundamental frequency (F0) and frequencies of the first and second formant (F1, F2) were calculated for each Japanese vowel. RESULTS AND CONCLUSIONS: The mLE1s for /u/ in males, and /o/ in females and the F2s for /i/ and /u/ in males, changed significantly after BSSRO. Class III voice characteristics were observed in the mLE1s for /i/ in both males and females, in the F0 for /a/, /i/, /u/ and /o/ in females, and in the F1 and F2 for /a/ in males, and the F1 for /u/ and the F2 for /i/ in females. Most of these characteristics were preserved after BSSRO.
    Journal of cranio-maxillo-facial surgery: official publication of the European Association for Cranio-Maxillo-Facial Surgery 03/2012; · 1.25 Impact Factor
  • Source
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    ABSTRACT: Objectives. To clarify the difference between Lyapunov exponents (LEs) for cleft palate (CP) patients with hypernasality versus without hypernasality and to investigate the relationship between their LEs and nasalance scores (NSs). Material and Methods. Six CP patients with severe hypernasality (mean age 9.2 years) and six CP patients without hypernasality (mean age 8.0 years) were enrolled. Five Japanese vowels were recorded at 44.1 KHz, and the NSs were measured simultaneously. The mean first LE (mLE(1)) from all one-second intervals was computed. Results. The mLE(1) for /o/ in patients with hypernasality was significantly higher than that in patients without hypernasality. The correlation coefficients between the mLE(1) and NS for all vowels were not statistically different. Conclusion. The voice signal of /o/ for the patients with hypernasality was more instable than in those without hypernasality. The chaotic phenomenon was independent of nasal resonance in CP voice.
    International Journal of Otolaryngology 01/2012; 2012:739523.
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    ABSTRACT: We analyzed 10 adenoid cystic carcinomas (ACCs) of the salivary glands by array-based comparative genomic hybridization (a-CGH) using DNA chips spotted with 4,030 bacterial artificial chromosome clones. After the data smoothing procedure was applied, a total of 88 DNA copy number aberrations (DCNAs) were detected. The frequent (≥30%) DCNAs were loss of 6q23-27 and 8p23, and gains of 6p, 6q23, 8p23 and 22q13. High-level gains were detected on 12q15, including MDM2 in two cases. These two cases showed an immunohistochemically high-level (>50%) expression of MDM2 and a low-level expression of p53 (<20%). Furthermore, the total number of DCNAs was significantly greater in ACCs with loss of 6q compared to other ACCs, and in ACCs without the loss of 8p23 compared to other ACCs, respectively. Although limitations exist, a-CGH detected several candidate chromosomal imbalances associated with accumulation of DCNAs in ACCs.
    Oncology Reports 09/2011; 26(6):1393-8. · 2.30 Impact Factor
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    ABSTRACT: Oral squamous cell carcinoma (OSCC) is a common malignancy worldwide and the prognosis for patients with advanced-stage OSCC is particularly poor. To identify DNA copy number aberrations and candidate genes associated with a poor or favorable outcome, we analyzed the genome profiles of OSCC tumors by array-based comparative genomic hybrid-ization (A-CGH). This technique uses DNA microarray technology to detect genomic copy number variations at a higher resolution level than chromosome-based CGH. Fifty patients with primary OSCCs were included in the study. Of these 50 patients, 37 were treated surgically and 13 were treated without surgery and had received irradiation and/or chemotherapy. All samples were analyzed by A-CGH. Gains were detected frequently (>50%) at chromosomal regions 5p15.33, 7p22.3, 8q21.1-24.3, 9q34.3, 11q13, 16p13.3 and 20q13.3. Losses were frequently detected at 3p22, 3p14 and 4q35.2. High-level gains were recurrently (>10%) detected at each of 5p15, 7p22, 7p11, 8q24, 11q13, 11q22 and 22q11. Gains of 2p25.1, 11p15, 16p13.3, 16q24.3 and 20q13.3 were inversely correlated with nodal metastasis. In 37 of the 50 OSCC patients treated with surgery, gains of 8q12.1-24.22 and losses of 3p26.2-3 were associated with disease-specific survival (p<0.01). Loss of a 0.2 Mb chromosomal region in 3p26.3 was associated with a poor prognostic outcome in the Kaplan-Meier analysis (p<0.01 by the log-rank test). Multivariate analysis revealed that loss of 3p26.3 is an independent prognostic factor (p<0.01) of OSCC. Loss of a 0.2 Mb chromosomal region in 3p26.3 including the CHL1 (cell adhesion molecule with homology to L1CAM1) gene was identified as a novel potential marker for predicting the prognosis of patients with OSCC.
    Oncology Reports 08/2011; 26(2):463-9. · 2.30 Impact Factor
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    ABSTRACT: It has previously been demonstrated that apatite may be coated on the surface of titanium (Ti) at room temperature when the titanium is blasted with apatite powder. This method is known as the blast coating (BC) method. In this study, the osteoconductivity and tissue response to Ti implants blast-coated with apatite (BC implants) were evaluated using apatite-coated Ti implants produced using the flame spraying (FS) method (FS implants) and pure Ti implants as a control. Initial evaluation using simulated body fluid demonstrated higher osteoconductivity in BC implants than in FS implants. Therefore, specimens were implanted in rat tibias for 1, 3 and 6 weeks. At one week after implantation, BC implants showed much higher bone contact ratio when compared with FS implants; the bone contact ratio of BC implants was 75.7%, while the FS and pure Ti implants had ratios of 30.8% and 5.5%, respectively. The difference in bone contact ratio between BC and FS implants decreased with implantation time and the ratios were equal after 6 weeks. In conclusion, BC implants show higher osteoconductivity than FS implants, and thus BC implants are beneficial for early fixation of implants to bone tissue.
    Dental Materials Journal 07/2011; 30(4):431-7. · 0.81 Impact Factor
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    ABSTRACT: The understanding of tumour progression is one of the most important strategies to conquer tumour. QR-32 is a regressive murine fibrosarcoma cell line, and QRsP-11 is a progressive malignant tumour cell clone derived from QR-32. Ina recently published study a differential display analysis for the cytoplasmic proteins was shown by using two-dimensional gel electrophoresis (2-DE) making full use of isoelectric focusing capillary gels and Coomassie brilliant blue R-250 staining. Furthermore, a differential display analysis of the nuclear proteome for QR-32 and QRsP-11 was performed. The present study shows a non-nuclear proteomic differential display analysis, using 2-DE making full use of immobilized pH gradient strips and Flamingo™ fluorescent gel stain, between QR-32 and QRsP-11 to identify particular proteins which may be involved in malignant progression. In QRsP-11 25 proteins were up-regulated, including hypoxia up-regulated protein 1, and 6 were down-regulated compared with QR-32. These results suggest that the identified non-nuclear proteins showing different expression between QR-32 and QRsP-11 possibly related to malignant tumour progression.
    Anticancer research 04/2011; 31(4):1259-63. · 1.71 Impact Factor
  • Oral Oncology - ORAL ONCOL. 01/2011; 47.
  • Oral Oncology - ORAL ONCOL. 01/2011; 47.
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    ABSTRACT: Mucinous adenocarcinoma (MAC) is a rare malignancy in the minor salivary gland. To our knowledge, genomic alterations in this tumor have not been reported previously. To identify DNA copy number aberrations, we applied comparative genomic hybridization (CGH) to four samples of MAC in minor salivary gland derived from two patients: a primary tumor and two cervical metastatic lymph nodes from one patient, and a primary tumor from the other patient. Copy number increases were commonly detected in 1q21∼q31 and 20q13, and these may play an important role in MAC carcinogenesis. Copy number increases in 1q, 12p, 12q, and 20q were commonly detected in all three samples derived from patient 1, and gain of 7p and loss of chromosome 4 were additionally detected in the two samples derived from metastatic lymph nodes. Amplifications were also detected in the chromosomal regions 8q22∼qter, 12p11∼p12, 12q11∼q21, and 20q13. Amplification of MDM2 (12q15) and of AURKA (20q13) was detected with fluorescence in situ hybridization. The DNA copy number aberrations detected in MAC in minor salivary glands were different from those reported for colorectal MAC. The present findings are novel in identifying genomic alterations of MAC arising from the minor salivary gland.
    Cancer genetics and cytogenetics 12/2010; 203(2):324-7. · 1.54 Impact Factor

Publication Stats

3k Citations
829.43 Total Impact Points

Institutions

  • 2005–2013
    • Yamaguchi University
      • Division of Oral and Maxillofacial Surgery
      Yamaguti, Yamaguchi, Japan
  • 1988–2009
    • Central Institute for Experimental Animals
      Kawasaki Si, Kanagawa, Japan
  • 2008
    • Nippon Veterinary and Life Science University
      Edo, Tōkyō, Japan
    • The University of Tokushima
      • Department of Therapeutic Regulation for Oral Tumors
      Tokusima, Tokushima, Japan
  • 2002–2003
    • Tottori University
      • Faculty of Medicine
      TTJ, Tottori, Japan
    • Ehime University
      • Department of Oral and Maxillofacial Surgery
      Matuyama, Ehime, Japan
  • 1994–2002
    • Okayama University
      • Department of Biomaterials
      Okayama, Okayama, Japan
  • 2001
    • Aichi Cancer Center
      Ōsaka, Ōsaka, Japan
  • 1996–2001
    • Keio University
      • Department of Internal Medicine
      Tokyo, Tokyo-to, Japan
  • 1984–2001
    • Tokai University
      • • Department of Pathology
      • • School of Medicine
      Hiratuka, Kanagawa, Japan
  • 1993–1998
    • Kanagawa Academy of Science and Technology
      Kawasaki Si, Kanagawa, Japan
  • 1997
    • Shinshu University
      • Department of Dermatology
      Shonai, Nagano, Japan
  • 1990
    • Tokyo Medical and Dental University
      • Department of Hygiene and Oncology
      Edo, Tōkyō, Japan
  • 1988–1989
    • Japanese Foundation for Cancer Research
      Edo, Tōkyō, Japan
  • 1987–1988
    • Tokyo Metropolitan Komagome Hospital
      Edo, Tōkyō, Japan
  • 1986
    • The University of Tokyo
      • Institute of Medical Science
      Tokyo, Tokyo-to, Japan