術後に顎関節に疼痛を訴えた顎偏位を伴う骨格性上顎前突症例

術後に顎関節に疼痛を訴えた顎偏位を伴う骨格性上顎前突症例

The Journal of Chu-Shikoku Orthodontic Society

中·四国矯正歯科学会雑誌


Analysis of the sublingual artery using contrast-enhanced computed tomography

This in vivo study aimed to clarify the position of the sublingual artery (SLA) relative to the mandibular bone and to infer the potential risk for injury during dental implant surgery. Contrast-enhanced computed tomography images of the mouth of 50 edentulous patients (100 sides) treated at Tokushima University Hospital were reviewed. Curved planar reconstructed images perpendicular to the alveolar ridge were processed and classified into molar, premolar, canine, and incisor regions. The SLA and its branches were identified, and the distance from the mandible to the SLA was measured. The SLA was located close to the mandible (<2 mm) in the molar, premolar, canine, and incisor segments in 12.0% (95% confidence interval 5.6%-18.4%), 20.6% (12.6%-28.7%), 30.5% (21.3%-39.8%), and 41.8% (28.8%-54.9%) cases, respectively. The SLA was located within ±3 mm craniocaudally to the upper wall of the mandibular canal in the molar and premolar regions in 50% of cases and within ±5 mm craniocaudally to the mylohyoid ridge in the canine and incisor regions in the other cases, with no sex or age-related differences. The vertical distance from the alveolar ridge to the SLA was influenced by sex and age owing to alveolar resorption, indicating that the alveolar ridge is not a reliable reference for predicting SLA position. As the risk of SLA injury always exist during dental implant placement and there is no way to confirm the SLA pathways in a patient, clinicians must avoid injuring the sublingual soft tissue.

Clinical Implant Dentistry and Related Research


A case of fishbone in the tongue that migrated toward the hyoid bone

舌骨近傍に移動した舌内迷入魚骨の1例

Japanese Journal of Oral & Maxillofacial Surgery


Computed tomography-based morphological analysis for intraoral vertical ramus osteotomy in patients with mandibular prognathism


Comparison of bioresorbable bone substitutes, carbonate apatite and β-tricalcium phosphate, for alveolar bone augmentation with simultaneous implant placement.


Reconstruction of rabbit mandibular bone defects using carbonate apatite honeycomb blocks with an interconnected porous structure.

Carbonate apatite (COAp) granules are useful as a bone substitute because they can be remodeled to new natural bone in a manner that conforms to the bone remodeling process. However, reconstructing large bone defects using COAp granules is difficult because of their granular shape. Therefore, we fabricated COAp honeycomb blocks (HCBs) with continuous unidirectional pores. We aimed to elucidate the tissue response and availability of COAp HCBs in the reconstruction of rabbit mandibular bone defects after marginal mandibulectomy. The percentages of the remaining COAp area and calcified bone area (newly formed bone) were estimated from the histological images. COAp area was 49.1 ± 4.9%, 30.3 ± 3.5%, and 25.5 ± 8.8%, whereas newly formed bone area was 3.0 ± 0.6%, 24.3 ± 3.3%, and 34.7 ± 4.8% at 4, 8, and 12 weeks, respectively, after implantation. Thus, COAp HCBs were gradually resorbed and replaced by new bone. The newly formed bone penetrated most of the pores in the COAp HCBs at 12 weeks after implantation. By contrast, the granulation tissue scarcely invaded the COAp HCBs. Some osteoclasts invaded the wall of COAp HCBs, making resorption pits. Furthermore, many osteoblasts were found on the newly formed bone, indicating ongoing bone remodeling. Blood vessels were also formed inside most of the pores in the COAp HCBs. These findings suggest that COAp HCBs have good osteoconductivity and can be used for the reconstruction of large mandibular bone defects. The COAp HCB were gradually resorbed and replaced by newly formed bone.

Journal of Materials Science. Materials in Medicine


ピロカルピン塩酸塩を用いた口腔リンス法の有用性と安全性の検討

ピロカルピン塩酸塩を用いた口腔リンス法の有用性と安全性の検討


Association of PD L1 and ZEB 1 expression patterns with clinicopathological characteristics and prognosis in oral squamous cell carcinoma

Programmed cell death-1 (PD-1) and its ligand programmed cell death 1 ligand 1 (PD-L1) are immune checkpoint inhibitors that play an important role in the host immune avoidance mechanism of tumors. The relationship between PD-L1 expression and malignancy has been reported in various types of cancer, such as lung and gastric cancer. In addition, epithelial-mesenchymal transition (EMT) of cancer cells is deeply involved in the invasion and metastasis of cancer. It has been reported that zinc finger E-box binding homeobox 1 (ZEB-1), an EMT inducer, contributes to metastasis in pancreatic and colon cancer. The present study aimed to investigate the relationship between the expression patterns of two markers, PD-L1 and ZEB-1, and clinicopathological characteristics and prognosis of oral squamous cell carcinoma (OSCC). Biopsy or surgical excision specimens from 169 patients with OSCC were used in the present study. Immunohistochemical staining with monoclonal anti-PD-L1 antibody and anti-ZEB-1 antibody was conducted. Cases with >1% tumor cells positive for PD-L1 and those with >10% tumor cells positive for ZEB-1 were considered positive, respectively. The findings revealed that individual expression of PD-L1 and ZEB-1 in OSCC was not associated with tumor size, degree of differentiation or Yamamoto-Kohama invasion pattern classification. However, co-expression of PD-L1 and ZEB-1 was associated with higher cervical lymph node metastasis and a lower survival rate. In conclusion, the results of the present study indicated that co-expression of PD-L1 and ZEB-1 could serve as a potential marker for the prognosis of patients with OSCC.


Soluble Factor from Oral Cancer Cell Lines Inhibits Interferon-γ Production by OK-432 via CD40/CD40Ligand Pathway


Evaluation of anatomical references for locating the course of the posterior superior alveolar artery for dental implant surgery

This retrospective cohort study aimed to identify the best anatomical reference for predicting the posterior superior alveolar artery (PSAA) location. Computed tomographic images of 90 maxillary sinuses were evaluated. We studied five references, including the alveolar crest, maxillary sinus floor, zygomatoalveolar crest, hard palate and soft palate, and measured the distances between them and the PSAA. Variations in the distance were evaluated by the standard deviation and coefficient of variation (CV). The zygomatoalveolar crest was an unstable reference, owing to its high standard deviation and CV. The smallest CV was for the distance between the alveolar crest and PSAA, although the distance was smaller in edentulous jaws than dentulous jaws. The distance between the sinus floor and PSAA was larger in male and edentulous patients. The PSAA was detected in 40.0%, 44.4%, 54.4% and 56.7% of the sinus walls at the first and second premolar and the first and second molar positions, respectively. At these tooth positions, the respective heights above the hard palate were 11.2 ± 4.9, 8.2 ± 4.9, 6.2 ± 2.8 and 8.1 ± 2.9 mm. The hard palate was the most stable reference for predicting the location of the PSAA, irrespective of sex, age and dentition.

International Journal of Oral and Maxillofacial Surgery


A clinical study on malignant lymphomas arising in the oral region

口腔領域に発症した悪性リンパ腫の臨床的検討

We examined the clinical characteristics of 18 cases of malignant lymphomas arising in the oral region which were diagnosed at our department during the 11 years from 2008 to 2018. The patients consisted of 10 males and 8 females whose mean age was 70.2 years. The primary site was the upper gingiva in 10 cases (55.6%), and the initial symptoms were tumor mass and swelling in 15 cases (83.3%). Only 7 cases (38.9%) were clinically diagnosed as malignant lymphoma at first visit, but the other 11 cases were difficult to diagnose correctly. The various clinical symptoms such as mass formation and ulcer made differential diagnosis difficult, and a definitive diagnosis could not be obtained by only a single biopsy. Therefore, we examined whether blood test results might be used as an indicator of the diagnosis or not. Our results showed that LDH in 8 of 17 cases (47.1%) and sIL-2R in 11 of 16 cases (68.8%) were high values. Furthermore, we examined whether lymphocyte-monocyte ratio (LMR) helped the diagnosis or not. Thirteen of 17 cases (76.5%) showed a low value of LMR. There was a significant difference in LMR compared to non-malignant lymphoma patients. LMR in the blood tests was also considered to be a useful marker for the diagnosis.

2008年から2018年までの11年間に当科で口腔領域に発症した悪性リンパ腫の18例について臨床的特徴を調べた．患者は，平均年齢が70.2歳の男性10例，女性8例であった．原発部位の10例(55.6%)は上顎歯肉で，初期症状は15例(83.3%)で腫瘤と腫脹であった．7例(38.9%)が初診時に臨床的に悪性リンパ腫と診断されたが，その他の11例は正しく診断することが困難であった．腫瘤形成や潰瘍のような様々な臨床症状が診断を困難にしており，1回の生検では確定診断が得られなかった．そこで，血液検査値が診断の指標であるかどうかを検討した．われわれの結果は，17例中8例のLDH(47.1%)と16例中11例のsIL-2R(68.8%)が高い値を示していた．さらに，われわれはリンパ球/単球数比(LMR)が診断に役立つかどうかを調べた．LMRの値は，17例中13例(76.5%)が有意に低く，非ML患者と比較しても有意差を認めた．以上のことより，LMRの血液検査も診断の補助的なマーカーであると考えられた．

Journal of Japan Society for Oral Tumors


Inferior alveolar nerve paresthesia caused by the extrusion of calcium hydroxide-based paste into themandibular canal: A case report.

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology


Expression of CD44,CD44v9ABCG2, CD24,Bmi-1 and ALDH1 in stage andoral spuamous cell carcinoma and their association with clinicopathological factors

Cancer stem cells (CSCs) exhibit self-replication, self-differentiation, drug resistance and immune evasion activities. In recent years CSCs have become increasingly important for the treatment of malignant tumors. CSCs express specific markers, including cluster of differentiation (CD)44, CD44 variant 9 (CD44v9), ATP-binding cassette sub-family G member 2 (ABCG2), CD24, B lymphoma Mo-MLV insertion region 1 homolog (BMI-1) and aldehyde dehydrogenase 1 (ALDH1). However, the prognostic value of their expression in patients with oral squamous cell carcinoma (OSCC) are not well known. The present study evaluated these markers in stage I and II patients with OSCC and examined the association between T classification, histological differentiation, classification of invasion mode, lymph node metastasis and disease-free survival rate. Tissue specimens were obtained from 70 patients with stage I or II OSCC following either surgery or biopsy. Immunohistochemistry was performed and positive staining was defiend as 10% positive cells. CD44 and CD44v9 expressions were strongly detected in all OSCC tissues compared with normal epithelial cells. A total of 22 (31.4%) cases expressed ABCG2 and there was a significant association between ABCG2 expression and invasion. A total of 41 cases (59.0%) expressed CD24 and there was a significant association between CD24 expression and invasion. A total of 33 cases (47.1%) expressed BMI-1 and there was a significant association between BMI-1 expression and the disease-free survival rate. A total of 18 cases (25.7%) expressed ALDH1. Although there was no association between ALDH1 expression and T classification, there were significant associations between ALDH1 expression and histological differentiation, invasion mode, metastasis and the disease-free survival rate. Multivariate analysis revealed that ALDH1 expression was the only prognostic factor for disease-free survival rate. The results of the present study suggest that the positivity of ALDH1 detected in patients with OSCC correlates with the number of cells undergoing epithelial mesenchymal transition and metastasis. These findings indicated that the expression of ALDH1 may be an effective prognostic marker indicating the survival of patients with stage I and II OSCC.


Palonosetron Prevents Highly Emetogenic Chemotherapy-induced Nausea and Vomiting in Oral Cancer Patients

To evaluate the efficacy of palonosetron in preventing acute and delayed nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC) in oral cancer patients. Oral cancer patients receiving HEC were enrolled; among the 40 patients, 87 courses of chemotherapy were administered. On day 1, 0.75 mg palonosetron was intravenously administrated just before chemotherapy. The primary endpoint was the proportion of patients with a complete response (CR) and the secondary endpoint was the proportion of patients with complete control (CC) during the acute and delayed phase. During the acute phase, 86 of 87 courses (98.9%) had CR and 84 of 87 courses (96.6%) had CC. During the delayed phase, 84 of 87 courses (96.6%) had CR and 70 of 87 courses (80.5%) had CC. Palonosetron is effective at preventing HEC-induced chemotherapy-induced nausea and vomiting (CINV) in oral cancer chemotherapeutic regimens in the acute and delayed phases.


徳島県における口腔がん検診の現状

徳島県における口腔がん検診の現状

日本歯科人間ドック学会誌

日本歯科人間ドック学会誌


Single non-contact Nd: YAG laser irradiation treatment for venous malformations in the oral cavity


Prevalence and imaging characteristics of palatine tonsilloliths evaluated on 2244 pairs of panoramic radiographs and CT images.

Palatine tonsilloliths incidentally detected on diagnostic imaging should be differentiated from pathologic calcifications to enable correct diagnosis and treatment. The aim of this study is to clarify the prevalence and imaging characteristics of palatine tonsilloliths on panoramic radiographs. We retrospectively reviewed 2244 individuals who underwent pairs of consecutive panoramic radiography and computed tomography (CT) of the head and neck region. The imaging characteristics of palatine tonsilloliths on panoramic radiography were compared with the findings from CT, which was considered the gold standard. Tonsilloliths were detected in 300 (13.4 %) and 914 (40.7 %) of the 2244 individuals on panoramic radiographs and CT, respectively. On panoramic radiographs, tonsilloliths were superimposed over the ramus of the mandible at the level coincident with and inferior to the soft palate in 176 (7.8 %) and 90 (4.0 %) individuals, respectively. Tonsilloliths were also superimposed over the surrounding soft tissue inferior to the body of the mandible, postero-inferior to the angle of the mandible, and posterior to the ramus of the mandible in 33 (1.5 %), 26 (1.2 %), and 28 (1.3 %) individuals, respectively. A significant correlation was observed between the detectability on panoramic radiographs and the size (Spearman r = 1.000) and number (Spearman r = 0.991) of tonsilloliths, as revealed by CT images. The present results suggest that tonsilloliths are commonly detected on panoramic radiographs. Furthermore, they can be superimposed on both the mandible and the surrounding soft tissue. Clinicians should include tonsilloliths among the differential diagnoses when calcified bodies are detected on panoramic radiographs.


Effectiveness of Newly Developed Water-Equivalent Mouthpiece during External Beam Radiotherapy for Oral Cancer


口腔がん患者の歯科疾患罹患状況

口腔がん患者の歯科疾患罹患状況

日本歯科人間ドック学会誌

日本歯科人間ドック学会誌


Fabrication and Physical Evaluation of Gelatin-Coated Carbonate Apatite Foam

Carbonate apatite (CO3Ap) foam has gained much attention in recent years because of its ability to rapidly replace bone. However, its mechanical strength is extremely low for clinical use. In this study, to understand the potential of gelatin-reinforced CO3Ap foam for bone replacement, CO3Ap foam was reinforced with gelatin and the resulting physical characteristics were evaluated. The mechanical strength increased significantly with the gelatin reinforcement. The compressive strength of gelatin-free CO3Ap foam was 74 kPa whereas that of the gelatin-reinforced CO3Ap foam, fabricated using 30 mass % gelatin solution, was approximately 3 MPa. Heat treatment for crosslinking gelatin had little effect on the mechanical strength of the foam. The gelatin-reinforced foam did not maintain its shape when immersed in a saline solution as this promoted swelling of the gelatin; however, in the same conditions, the heat-treated gelatin-reinforced foam proved to be stable. It is concluded, therefore, that heat treatment is the key to the fabrication of stable gelatin-reinforced CO3Ap foam.


Measurement of the zygomatic bone and pilot hole technique for safer insertion of zygomaticus implants

The zygomaticus implant was developed for patients with severe bone resorption of the posterior maxilla. These may eliminate or minimize the need for bone grafting. Although the zygomaticus implant has shown a remarkable success rate in this difficult-to-treat patient population, the method requires an advanced surgical technique and carries an increased risk of complications. There have been few anatomical studies on the zygomatic bone in relation to the insertion of zygomaticus implants. The height and thickness of the zygomatic bone for the insertion were measured in this study. The thickness at the 90° angle point, where the upper margin of the zygomatic arch and the temporal margin of the frontal process of the zygomatic bone intersect and where the apex of the implant penetrates, was found to be 1.8±0.4 mm; this gradually increased inferiorly and anteriorly. Thus, the penetration point of the apex of the zygomaticus implant should be located more inferoanterior to the 90° angle point, as the thickness in this region is thinner than the diameter of the implant. Based on the results of this study, a newer and safer insertion method for the zygomaticus implant using a drill guide is proposed.

International Journal of Oral and Maxillofacial Surgery


Effects of low crystalline carbonate apatite on proliferation and osteoblastic differentiation of human bone marrow cells

Carbonated apatite (CO3Ap) is the inorganic component of bone. We have proposed a new method for the fabrication of CO3Ap blocks based on a dissolution-precipitation method using a synthetic precursor. The aim of this study is to examine the effects of low crystalline CO3Ap on initial cell attachment, proliferation and osteoblastic differentiation of human bone marrow cells (hBMCs) using sintered hydroxyapatite and tissue culture plates as controls. Initial cell attachment and proliferation were assessed with a MTT assay. Expression of osteoblastic markers was examined by reverse transcription-polymerase chain reaction. XRD and FT-IR results showed formation of B-type carbonate apatite with lower crystallinity. No difference was observed for initial cell attachment between HAp and CO3Ap discs. hBMSC attached more significantly on tissue culture plate than on HAp and CO3Ap discs. The number of cells on HAp was higher than that on CO3Ap until day 7, after which the number of cells was similar. hBMSC proliferated more significantly on tissue culture plate than on HAp and CO3Ap discs. In contrast, hBMCs incubated on CO3Ap demonstrated much higher expression of osteoblastic markers of differentiation, such as type I collagen, alkaline phosphatase, osteopontin and osteocalcin, than hBMCs on HAp. On the tissue culture plate, they were not any change throughout the culture period. These results demonstrated that low crystalline CO3Ap exhibit higher osteoinductivity than HAp.

Journal of Materials Science. Materials in Medicine


Antitumour effect of valproic acid against salivary gland cancer in vitro and in vivo

Salivary gland cancer (SGC) has a comparatively poor prognosis and is prone to frequent recurrence and metastases. Therefore, the development of more effective chemotherapy against SGC is desirable. The aim of the present study was to investigate the antitumour effects of valproic acid (VPA) against SGC in vitro and in vivo. Two human SGC cell lines (HSY and HSG cells) were used in the present study. The effects of VPA on the proliferation of SGC cells in vitro were assessed by MTT assay. Cancer cells treated with VPA were subjected to cell cycle analysis by flow cytometry. In addition, the expression levels of p21 and p27 were examined by real-time RT-PCR to identify the mechanisms of the antitumour effect of VPA on SGC. The effects of VPA on cancer growth in vivo were evaluated in a xenograft model. VPA inhibited the proliferation of SGC cells in a dose-dependent manner in vitro. Degenerated cancer cells were observed at high concentrations of VPA. In the cell cycle analysis, VPA induced cell-growth inhibition and G1 arrest of cell cycle progression in both cancer cell lines in a time- and dose-dependent manner. VPA markedly upregulated the mRNA expression levels of both p21 and p27 in both SGC cell lines in a time-dependent manner. In the xenograft model experiment, VPA treatment markedly inhibited the growth of salivary gland tumours when compared with the growth of the untreated controls. VPA may be a valuable drug in the development of better therapeutic regimens for SGC.


The Role of Metabotropic Glutamate Receptor 5 on the Stromal Cell-Derived Factor-1/CXCR4 System in Oral Cancer

We have demonstrated that blocking CXCR4 may be a potent anti-metastatic therapy for CXCR4-related oral cancer. However, as CXCR4 antagonists are currently in clinical use to induce the mobilization of hematopoietic stem cells, continuous administration as an inhibitor for the metastasis may lead to persistent leukocytosis. In this study, we investigated the novel therapeutic downstream target(s) of the SDF-1/CXCR4 system, using B88-SDF-1 cells, which have an autocrine SDF-1/CXCR4 system and exhibit distant metastatic potential in vivo. Microarray analysis revealed that 418 genes were upregulated in B88-SDF-1 cells. We identified a gene that is highly upregulated in B88-SDF-1 cells, metabotropic glutamate receptor 5 (mGluR5), which was downregulated following treatment with 1,1' -[1,4-Phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane octahydrochloride (AMD3100), a CXCR4 antagonist. The upregulation of mGluR5 mRNA in the SDF-1/CXCR4 system was predominately regulated by the Ras-extracellular signal-regulated kinase (ERK)1/2 pathway. Additionally, the growth of B88-SDF-1 cells was not affected by the mGluR5 agonist (S)-3,5-DHPG (DHPG) or the mGluR5 antagonists 2-Methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP). However, we observed that DHPG promoted B88-SDF-1 cell migration, whereas both MPEP and MTEP inhibited B88-SDF-1 cell migration. To assess drug toxicity, the antagonists were intraperitoneally injected into immunocompetent mice for 4 weeks. Mice injected with MPEP (5 mg/kg) and MTEP (5 mg/kg) did not exhibit any side effects, such as hematotoxicity, allergic reactions or weight loss. The administration of antagonists significantly inhibited the metastasis of B88-SDF-1 cells to the lungs of nude mice. These results suggest that blocking mGluR5 with antagonists such as MPEP and MTEP could prevent metastasis in CXCR4-related oral cancer without causing side effects.


Bortezomib-enhanced radiosensitization through the suppression of radiation-induced nuclear factor B activity in human oral cancer cells.

Oral cancer cells have a significantly augmented nuclear factor-κB (NF-κB) activity and the inhibition of this activity suppresses tumor growth. Bortezomib is a proteasome inhibitor and a drug used for molecular-targeted therapy (targets NF-κB). In this study, we investigated whether bortezomib would be effective as an inhibitor of proliferation and a radiosensitizer for the treatment of oral cancer. We demonstrate that bortezomib inhibits NF-κB activity and cell proliferation. The combined treatment with bortezomib and radiation (RT) suppressed NF-κB activity and cell growth in vitro and in vivo compared with RT treatment alone. To investigate the mechanisms by which bortezomib suppresses tumor growth, the expression of signaling molecules downstream of NF-κB were examined by ELISA. The combined treatment significantly inhibited the radiation-induced production of angiogenic factors and decreased the number of blood vessels in the tumor tissues. Although the expression of anti-apoptotic proteins was upregulated by RT, bortezomib downregulated the RT-induced expression of these proteins. Moreover, the expression of cleaved poly(ADP-ribose) polymerase in vitro and in vivo was enhanced by bortezomib, indicating that bortezomib inhibits tumor growth by inducing apoptosis. This study clearly demonstrates that bortezomib significantly inhibits tumor growth and that the combined treatment with bortezomib and RT results in a significant inhibition of tumor growth. The mechanisms underlying the inhibition of tumor growth by bortezomib include the suppression of angiogenesis and the induction of apoptosis. A novel molecular targeting therapy including bortezomib may be effective in the treatment of oral cancer by suppressing NF-κB activity.


A case of giant cell epulis accompanied by bone formation in the premolar region of the mandible

下顎小臼歯部に発生した骨形成を伴う巨細胞エプーリスの1例

Giant cell epulis (peripheral giant cell granuloma) is a granuloma consisting of a large number of multinucleated giant cells. Its incidence is high in Europe and the United States, but is very low in Japan. Giant cell epulis accompanied by bone formation is extremely rare in Japan. We report a case of giant cell epulis accompanied by bone formation. A 46-year-old woman visited our hospital because of a mass in the left mandibular molar region. There was a well-demarcated, pedunculated mass in the left mandibular molar region. The mass was excised under the clinical diagnosis of epulis. Histopathologically, the resected specimen consisted of spindle cells resembling fibroblasts and many multinucleated giant cells. Moreover, newly synthesized bone was observed in the center of the mass. The pathological diagnosis was a giant cell granuloma. Two years six months after the operation, there has been no evidence of recurrence.

Japanese Journal of Oral & Maxillofacial Surgery


Antitumor efficacy of sequential treatment with docetaxel and 5-fluorouracil against human oral cancer cells

Docetaxel (DOC) and 5-fluorouracil (5-FU) are important anticancer agents widely used in the treatment of a variety of cancers including oral squamous cell carcinoma (OSCC). The purpose of this study was to determine the antitumor efficacy of the sequential administration of DOC and 5-FU against OSCC cells (B88 and CAL27 cells) in vitro and in vivo. In in vitro growth inhibition assays, sequential treatment with DOC followed by 5-FU was more effective in inhibiting cancer cell growth than 5-FU followed by DOC, single treatment with DOC or 5-FU, or combined treatment with DOC and 5-FU. Furthermore, DOC followed by 5-FU significantly inhibited tumor growth in vivo compared to 5-FU followed by DOC. To understand the mechanisms underlying the enhanced growth inhibitory effect of the administration sequence, DOC followed by 5-FU, we examined the expression of 5-FU metabolic enzymes such as thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT), which were known to regulate the antitumor effect of 5-FU, by real-time RT-PCR and western blot analysis. Downregulation of TS and DPD expression and upregulation of OPRT expression were induced by DOC treatment, suggesting that DOC enhanced the efficacy of 5-FU by altering the expression of its metabolic enzymes. These results indicate that sequential treatment with DOC followed by 5-FU could be a promising therapeutic strategy for oral cancer.


[Evaluation of Combination Chemotherapy with Oral S-1 Administration Followed by Docetaxel by Superselective Intra-Arterial Infusion for Patients with Oral Squamous Cell Carcinomas.]

口腔扁平上皮癌に対するS-1を併用したDocetaxel超選択的動注化学療法の臨床効果に関する研究

The purpose of this study was to evaluate the effectiveness and adverse events of combination chemotherapy with oral S-1 administration following docetaxel(DOC)treatment by superselective intra-arterial infusion as neo-adjuvant chemotherapy (NAC)for patients with oral squamous cell carcinoma. Thirteen patients were enrolled in this study(9 men and 4 women, with a mean age of 61. 0 years). All patients were given S-1 65mg/m / 2 per day for 14 days, and DOC 40-50mg/m2 by intraarterial infusion was administered. The locoregional response evaluated 3 weeks after administration was 100%, including a 69. 2% complete response. According to Oboshi and Shimosato's classification, histological evaluation of surgical specimens revealed that 3 cases were Grade IIa, 4 cases Grade IIb, 1 case Grade IVa, and 4 cases Grade IVc. The severe side effects were neutropenia and cerebral infarction. The present study suggests that combination chemotherapy with S-1 and DOC by superselective intra-arterial infusion would be an effective and safe regimen in NAC for oral squamous cell carcinomas.

Japanese Journal of Cancer and Chemotherapy


A retrospective survey of conscious sedation used in children undergoing oral surgery or dental treatment during e ten-year period at the Tokushima University Hospital

小児患者の精神鎮静法に関する過去10年間の検討

Journal of Japanese Dental Society of Anesthesiology


分子標的薬bortezomibを用いた口腔癌に対する新規治療法の開発

分子標的薬bortezomibを用いた口腔癌に対する新規治療法の開発


Cepharanthin-enhanced radiosensitivity through the inhibition of radiation-induced nuclear factor-kappaB activity in human oral squamous cell carcinoma cells.

We have already demonstrated that human head and neck cancer cells have significantly enhanced levels of transcription factor nuclear factor (NF)-kappaB activity compared to their normal counterparts, suggesting that NF-kappaB plays an important role in the development of head and neck cancer. However, it has been reported that chemotherapeutic agents and radiation activate NF-kappaB activity in cancer cells, thus making the cells radioresistant and chemoresistant. In addition, we have shown that the suppression of NF-kappaB activity enhanced apoptosis in oral squamous cell carcinoma cells. In this study, we examined whether cepharanthin-induced inhibition of NF-kappaB activity enhances radiosensitivity in human oral carcinoma cells. Cepharanthin is a biscoclaurine alkaloid extracted from the roots of Stephania cepharantha hayata, and is widely used in Japan for the treatment of patients with leucopenia, nasal allergy, and venomous snakebites. gamma-irradiation (IR) induces NF-kappaB activity in oral carcinoma cells through the activation of upstream molecules, including Akt and IkappaB kinase. However, a luciferase assay revealed that cepharanthin suppresses IR-induced NF-kappaB activity in oral squamous cell carcinoma cells, thereby enhancing the radio-sensitivity. Western blot analysis showed an enhanced cleavage of poly-(ADP-ribose) polymerase protein in carcinoma cells by both cepharanthin treatment and IR exposure compared to IR or cepharanthin alone. In an in vivo study, B88 cells were s.c. inoculated into the backs of nude mice. Tumor-bearing nude mice received either cepharanthin, IR alone, or a combination of cepharanthin and IR. The combined treatment suppressed tumor growth significantly more than either cepharanthin or IR alone. Cepharanthin inhibited the production of IR-induced IL-6 and IL-8, which are downstream targets of NF-kappaB. In quantitative real-time RT-PCR, IR also induced the expression of anti-apoptotic proteins [cellular inhibitor of apoptosis protein (cIAP)-1 and -2] in carcinoma cells. Treatment of cancer cells with cepharanthin combined with exposure to IR decreased cIAP-1 and -2 mRNA expression. These findings suggested that the combination of radiotherapy and cepharanthin could enhance radiosensitivity in the treatment of human oral cancer.


Enhanced radiosensitization by cepharanthin in human oral squamous carcinoma cells : Inhibition of NF-κB as a molecular target

口腔扁平上皮癌細胞に対するセファランチンによる放射線感受性増強作用 : 分子標的NF-κBの抑制

Journal of The Japanese Stomatological Society