Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(公社)日本口腔インプラント学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(公社)日本口腔インプラント学会  

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Language：Japanese   Publisher：(一社)日本有病者歯科医療学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本口腔ケア学会  

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Language：Japanese   Publisher：(一社)日本口腔ケア学会  

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Language：Japanese   Publisher：(一社)日本口腔ケア学会  

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Language：Japanese   Publisher：(一社)日本口腔ケア学会  

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Language：Japanese   Publisher：(一社)日本口腔ケア学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本口腔診断学会  

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Language：Japanese   Publisher：(一社)日本有病者歯科医療学会  

脊髄硬膜外膿瘍は脊柱管内硬膜外に膿瘍を形成し,脊髄および脊髄根障害を引き起こすまれな疾患である.今回われわれは,口腔内細菌が起因菌と考えられた頸椎硬膜外膿瘍の1例を経験したので報告する.患者は63歳男性.既往歴は心房細動,緑内障,副鼻腔炎であった.頸部痛,咽頭痛,発熱を認め,咽後膿瘍疑いで当院耳鼻咽喉科を受診し,同日緊急入院となった.入院時の造影CT検査では同部に明らかな膿瘍形成は認めなかったため,整形外科に対診の結果,当初は頸長筋炎が疑われた.その後,第4病日に左側第二大臼歯相当部の疼痛精査目的に,当科紹介受診となった.パノラマエックス線検査,造影CT検査では,左側第二大臼歯根尖に透過像を認め,左側上顎洞底に近接していた.両側上顎洞,篩骨洞および蝶形骨洞に不透過像の亢進を認め,左側第二大臼歯根尖性歯周炎,両側副鼻腔炎と診断した.第7病日から再度熱発を認め,血液検査で炎症反応の増悪を認めた.造影CT検査では左側後咽頭間隙の軟部組織陰影の増大および頸椎C2～4の左側硬膜外に膿瘍形成を認めた.発熱と後頸部痛を認めたが,神経根症状は認めず,病期はI期の左側頸椎硬膜外膿瘍と診断した.左側上顎第二大臼歯の根尖病巣から上顎洞炎,篩骨洞炎,蝶形骨洞炎と炎症が波及し,後咽頭間隙を経由して頸椎硬膜外膿瘍を形成した可能性が考えられた.口腔内細菌を標的とし,第10病日からsulbactam/ampicillin(SBT/ABPC)12g/dayを開始し,消炎を行った.第12病日に原因歯と考えられた左側第二大臼歯の抜歯を行った.抜歯時に根尖から採取した検体より,血液培養でも陽性であったStreptococcus intermediusが検出された.第31病日までSBT/ABPC投与を継続したところ,頸椎硬膜外膿瘍は消退し,両側副鼻腔炎も改善を認めた.本症例では神経症状が出現する前に頸椎硬膜外膿瘍と診断されたため,保存的加療で後遺障害なく治癒した.(著者抄録)

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(公社)日本口腔インプラント学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本口腔ケア学会  

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Language：Japanese   Publisher：(一社)日本有病者歯科医療学会  

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Language：Japanese   Publisher：(一社)日本口腔診断学会  

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Language：Japanese   Publisher：(公社)日本口腔インプラント学会  

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Language：Japanese   Publisher：(一社)日本口腔内科学会  

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Language：Japanese   Publisher：(一社)日本有病者歯科医療学会  

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(一社)日本口腔ケア学会  

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Language：Japanese   Publisher：(一社)日本口腔診断学会  

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Language：Japanese   Publisher：(一社)日本口腔内科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

総合病院で入院加療を行った患者を対象に、口腔機能の現状や歯科医療ニーズに関する全国調査を実施した。2017年11月1日から11月30日もしくは2018年1月1日から1月31日の1ヵ月間に日本口腔科学会研修施設で入院加療を行った患者を対象に質問紙法を実施した。26医療機関より2280件(男性1223人、女性1057人、平均57.3歳)の回答を得た。口腔内に何らかの自覚症状をもつと回答した患者は1647人(72.2%)、なしと回答した患者は202人(8.9%)であった。口腔症状の内訳は口腔乾燥が370人(16.2%)、歯肉の疼痛・出血などの歯周炎が246人(10.8%)、義歯不適合169人(7.4%)などであった。入院中に口腔内の自覚症状が改善したと答えた患者は291人(12.8%)、悪化したと答えた患者は129人(5.7%)、変化なしと答えた患者は1705人(74.8%)であった。入院中に院内の歯科・口腔外科・口腔ケア外来等の歯科部門を受診した患者は415人(18.2%)にとどまっていた。入院中に主科で受けた治療内容と口腔症状の変化、口腔症状と食事形態に関する患者の意識を比較したところ、放射線治療を受けた患者に口腔症状の悪化を感じているものが多いことが判明した。

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01072&link_issn=&doc_id=20200807250001&doc_link_id=10.11277%2Fstomatology.69.179&url=https%3A%2F%2Fdoi.org%2F10.11277%2Fstomatology.69.179&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

総合病院で入院加療を行った患者を対象に、口腔機能の現状や歯科医療ニーズに関する全国調査を実施した。2017年11月1日から11月30日もしくは2018年1月1日から1月31日の1ヵ月間に日本口腔科学会研修施設で入院加療を行った患者を対象に質問紙法を実施した。26医療機関より2280件(男性1223人、女性1057人、平均57.3歳)の回答を得た。口腔内に何らかの自覚症状をもつと回答した患者は1647人(72.2%)、なしと回答した患者は202人(8.9%)であった。口腔症状の内訳は口腔乾燥が370人(16.2%)、歯肉の疼痛・出血などの歯周炎が246人(10.8%)、義歯不適合169人(7.4%)などであった。入院中に口腔内の自覚症状が改善したと答えた患者は291人(12.8%)、悪化したと答えた患者は129人(5.7%)、変化なしと答えた患者は1705人(74.8%)であった。入院中に院内の歯科・口腔外科・口腔ケア外来等の歯科部門を受診した患者は415人(18.2%)にとどまっていた。入院中に主科で受けた治療内容と口腔症状の変化、口腔症状と食事形態に関する患者の意識を比較したところ、放射線治療を受けた患者に口腔症状の悪化を感じているものが多いことが判明した。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01072&link_issn=&doc_id=20200807250001&doc_link_id=10.11277%2Fstomatology.69.179&url=https%3A%2F%2Fdoi.org%2F10.11277%2Fstomatology.69.179&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(一社)日本有病者歯科医療学会  

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Language：Japanese   Publisher：(一社)日本有病者歯科医療学会  

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Language：Japanese   Publisher：(一社)日本口腔腫瘍学会  

近年の治療法の向上にもかかわらず、約30年の間、早期口腔癌の治療成績は改善を認めていない。早期口腔癌における頸部リンパ節転移の有無は最も重要な予後因子である。それゆえに、頸部リンパ節転移の早期発見は予後の改善につながると考えられる。cN0症例における頸部マネージメントについては、経過観察もしくは予防的頸部郭清術のいずれかが選択されてきており、長年の論点となってきた。センチネルリンパ節生検は多くの領域で受け入れられている方法であり、口腔癌においては頸部郭清術の適否を判断する検査法である。本研究ではセンチネルリンパ節生検症例の同定部位、転移陽性レベル等から予防的頸部郭清術の適否について検討を行うとともに、今後の展望について述べる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本口腔腫瘍学会  

近年の治療法の向上にもかかわらず、約30年の間、早期口腔癌の治療成績は改善を認めていない。早期口腔癌における頸部リンパ節転移の有無は最も重要な予後因子である。それゆえに、頸部リンパ節転移の早期発見は予後の改善につながると考えられる。cN0症例における頸部マネージメントについては、経過観察もしくは予防的頸部郭清術のいずれかが選択されてきており、長年の論点となってきた。センチネルリンパ節生検は多くの領域で受け入れられている方法であり、口腔癌においては頸部郭清術の適否を判断する検査法である。本研究ではセンチネルリンパ節生検症例の同定部位、転移陽性レベル等から予防的頸部郭清術の適否について検討を行うとともに、今後の展望について述べる。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

Failure to detect recurrence and lymph node metastasis early represents a fundamental barrier to the improvement of survival rate in early stage oral squamous cell carcinoma (OSCC). The present study evaluated the association between serum interleukin-6 (IL-6) level and clinical outcomes in patients with early stage OSCC patients defined by sentinel node biopsy (SNB). A total of 53 patients with clinical stage I/II OSCC who underwent SNB were enrolled. SNB was determined by a radioisotope method, and was evaluated by histopathological examination and genetic analysis. Preoperative sera were measured for IL-6 by ELISA. In the clinical stage I/II patients, disease-free survival (DFS) was demonstrated to be higher in patients with negative SNB compared with patients with positive SNB. In total, 13 patients were demonstrated to exhibit lymph node metastasis by SNB or were reclassified to pathological stage T4 subsequent to analysis of the surgically resected specimens. Thus, 40 patients were diagnosed with early stage OSCC. Of these 40 patients, DFS of the patients with low serum IL-6 was significantly higher compared with the patients with high serum IL-6 (P=0.012). In 19 patients with negative SNB and low serum IL-6, the disease-free rate was 100%. These findings suggested that SNB staging and serum IL-6 level have a high prognostic value in patients with early stage OSCC. Additional investigation and longer follow-up times are warranted to improve understanding of the group of patients that may benefit from this procedure.

DOI： 10.3892/ol.2017.7183

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMJ Publishing Group  

DOI： 10.1136/bcr-2017-219344

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Language：Japanese   Publisher：一般社団法人 日本口腔腫瘍学会  

Cervical lymph node metastasis is an important prognostic factor in oral cancer. Whether patients with cN0 status should be treated with elective neck dissection or with therapeutic neck dissection after nodal relapse has been a matter of debate. Sentinel node biopsy (SNB) is a widely accepted procedure in various human malignancies. SNB has received considerable attention for its role in deciding whether to perform neck dissection. However, there are four issues in the current status of SNB in oral cancer: adopting the RI method, shine-through phenomenon, method of diagnosing occult metastasis, and establishment of EBM. This paper outlines the current status of SNB in oral cancer.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare malignant lesion of the jaws with a predilection to arise in the mandible of elderly men. We describe a case of PIOSCC derived from a dentigerous cyst lining in a 57-year-old man. No specific symptoms or radiographic features were present. A well-differentiated squamous cell carcinoma (SCC) was diagnosed after cyst extirpation along with three mandibular molars, whereas a biopsy specimen showed no malignant changes within the cyst lining. Because SCC was localized to the cyst wall, and there was no evidence of metastasis on computed tomography 1 month after operation, additional resection and adjuvant therapy were not performed. We have closely followed up the patient for more than 5 years. No evidence of recurrence or metastasis has been detected.

DOI： 10.1016/j.ajoms.2015.12.007

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DOI： 10.1016/j.ijom.2015.05.008

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

Oncogene addiction can provide therapeutic opportunities in human malignancies. In this study, we aimed to identify critical oncogenes for oral squamous cell carcinoma (OSCC) development and progression. We determined gene expression profiles in 10 primary OSCCs and 10 human OSCC cell lines using Applied Biosystems Human Genome Survey Arrays. Akt1 was the only gene identified that was expressed in all OSCC tissues and cultured cells, but not in non-neoplastic tissues and cells. Subsequently, western blot analysis showed that Aka protein was overexpressed in OSCC tissues and cell lines. Immunohistochemistry also showed Akt1 protein expression in 59 of 63 (94%) primary OSCCs. To clarify the oncogenic function of Akt1 in human OSCC cells, we used RNA interference. We designed and synthesized 5 small interfering RNAs specific for Akt1 (siAkt1). Transfecting human OSCC cells with siAkt1 in vitro markedly suppressed their expression of Akt1 protein and significantly reduced their growth rate. Furthermore, the growth of human OSCC tumors which had been subcutaneously xenografted in athymic nude mice lacking interferon responses was markedly inhibited by atelocollagen-mediated systemic siAkt1 administration. We also found that synthetic siAkt1 had an inhibitory effect on the growth of primary cultured OSCC cells. Finally, we investigated the molecular mechanisms involved in the growth inhibitory effect of Akt1 suppression using microarray analysis of human OSCC cells transfected with siAkt1. Knockdown of Aka induced the expression of CDKN2B, a tumor suppressor gene, and reduced the expression of TGFBR1, which supports malignant phenotypes. These results suggest that Aka functions as a critical oncogene in human OSCC cells and may therefore be an appropriate target for novel OSCC therapies.

DOI： 10.3892/ijo.2015.3134

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Language：Japanese   Publisher：日本医師会  

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: We examined whether general dentists can contribute to the detection of patients with undiagnosed diabetes and prediabetes by monitoring blood glucose in dental clinics. RESEARCH DESIGN AND METHODS: A total of 716 patients who visited clinics for dental treatment were enrolled and classified into 3 groups (mild, moderate, and severe) according to Kornman's criteria for periodontitis. The correlations between the casual blood glucose level, presence or absence of the history of diabetes, and/or severity of periodontitis were evaluated. RESULTS: 68 patients (9.5%) had hyperglycemia (blood glucose ≥200 mg/dL). Of these patients, 20 (29.4%) did not have a history of diabetes. Blood glucose tended to be higher with greater periodontitis severity. Of the 3 groups, the severe periodontitis group had the highest proportion of patients with hyperglycemia (p<0.0001). CONCLUSIONS: Patients with dental problems could be screened for diabetes, especially undiagnosed diabetes. General dentists could function as practitioners to screen for diabetes. TRIAL REGISTRATION NUMBER: UMIN-CTR 000014877.

DOI： 10.1136/bmjdrc-2015-000151

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Language：Japanese   Publisher：愛媛医学会  

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Language：Japanese   Publisher：社団法人 日本口腔外科学会  

Tocilizumab, a humanized anti-interleukin 6 receptor antibody, has been reported to be effective for chronic rheumatoid arthritis (RA) in clinical trials and was approved in Japan for the first time in the world in April 2008. We report a patient with methotrexate (MTX)-associated lymphoproliferative disorder in whom bisphosphonate-related osteonecrosis of the jaw (BRONJ) was exacerbated by concurrent treatment with tocilizumab. &lt;br&gt;A 60-year-old woman was referred to our department by her dentist because of diffuse swelling of the right submandibular region and a right lower gingival ulcer. Computed tomography showed extensive swelling of the cervical, axillary, subscapular, and inguinal lymph nodes. Her medical history included RA. She had received MTX and sodium risedronate hydrate. Her past medical history and present illness strongly suggested BRONJ. Bisphosphonate administration was terminated, and BRONJ was treated conservatively with antibiotics and local irrigation. Because RA was getting worse, she was given tocilizumab. Subsequently, gingival necrosis and BRONJ was apparently exacerbated. Tocilizumab and MTX were withdrawn, and she received antibiotics and surgical treatment. There have been no signs of recurrence for 18 months.

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

A number of regimens composed of concurrent chemoradiotherapy (CCRT) have been attempted as radical or adjuvant therapies for locally advanced oral cancer. CCRT with S-1 is considered promising due to its efficacy and simplicity of application. Patients (n=16) with locally advanced squamous cell carcinoma of the oral cavity were enrolled. Chemotherapy consisted of oral administration of S-I (65 mg/m(2)) for 14 consecutive days followed by a 1-week rest. Radiation treatment at a dose of 30 Gy in 15 fractions was administered concomitantly with S-1. A course schedule of 3 weeks of treatment was applied twice. The overall response rate was 87.5%. Median progression-free survival and median overall survival were 6.3 and 42.5 months, respectively. Although no grade 4 adverse events were observed, grade 3 adverse events, such as anemia (12.5%), stomatitis (25%) and anorexia (18.8%) were present. Thus, CCRT with S-1 is an effective modality that can be safely conducted with minimal burden on patients.

DOI： 10.3892/ol.2011.347

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC CANCER RESEARCH  

TNF-related apoptosis-inducing ligand (TRAIL) is a current focus for the development of new cancer therapies, because of its selective induction of apoptosis in cancer cells. TRAIL has previously been shown to be important for tumor cell clearance from the liver; however, many cancer cell lines show some resistance toward TRAIL, posing a problem for the future use of TRAIL therapies. In this study, we show that interfering with a cell&apos;s ability to attach and spread onto a matrix can sensitize tumor cells to TRAIL-induced apoptosis in vitro. We targeted different members of the integrin signaling pathway using siRNA or inhibitors, including beta-integrins, talin, Src, and downstream survival pathways PI3K and MAPK. Targeting any of these molecules could sensitize both MDA-MB-231 human breast cancer cells and TRAIL-resistant 1205Lu melanoma cells to TRAIL-induced apoptosis in vitro. Transcriptionally targeting the cytoskeleton, using myocardin-related transcription factor depletion to disrupt the transcription of cytoskeletal proteins, also caused TRAIL sensitization in MDA-MB-231 cells. We showed that this sensitivity to TRAIL correlated with increased activation of the intrinsic pathway of apoptosis. Manipulation of cell spreading therefore presents a potential method by which disseminated tumor cells could be sensitized to TRAIL therapies in vivo. Mol Cancer Res; 9(3); 249-58. (C) 2011 AACR.

DOI： 10.1158/1541-7786.MCR-11-0021

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Dendritic cell (DC) function will likely be important for immunological cancer therapies, but our knowledge of the roles of DCs in tumors is limited, in part because most studies were performed before DC subtypes were defined. We studied the distributions of immature epidermal, immature dermal, mature, and plasmacytoid DCs in 63 primary tumors and eight lymph node metastases from oral squamous cell carcinoma patients without evidence of distant metastasis. Immature CD207/Langerin+ and CD209/DC-SIGN+ DCs were present in the primary tumor region, but CD209/DC-SIGN+ cells rarely infiltrated the tumor. Mature DCs were rare, and presence of CD123+ plasmacytoid DCs was associated with poorer outcome. Unexpectedly, migration and maturation of DCs was associated with a worse outcome. Overall, the distribution of DC subtypes indicated that ineffective DC response to tumor is a failure of DC function rather than recruitment, suggesting that a strategy of shifting the balance of secreted factors in the tumor milieu may be more effective in restoring anti-tumor immune function than current methods restoring only one population of DCs to the immunosuppressive tumor region. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.canlet.2007.04.003

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE  

P16 promoter methylation Occurs frequently in oral squamous cell carcinoma (OSCC). For the early detection of tumour-related aberrant DNA, we examined p16 methylation using the methylation-specific polymerase chain reaction (MSP) in tumour and serum samples of 17 OSCC patients. Aberrant p16 methylation was detected in 11 (64.7%) cases of primary OSCC. Of these 11 patients, 6 (54.5%) showed the same alteration in their serum. No methylation was found in control groups. Interestingly, DNA was detected in the serum of 3 out of 4 patients with recurrence. These results Suggest that the MSP may be a sensitive and useful method for detecting recurrent OSCC.

DOI： 10.1016/j.ijom.2005.08.005

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Language：Japanese   Publisher：(株)癌と化学療法社  

口腔癌再発例では,しばしば切除不能となり治療法の選択に苦慮することがある.特に放射線照射後の再発において,どのような抗癌剤を選択するかは難しい問題である.われわれは口腔癌切除不能再発例に対し,collagen gel droplet embedded culture sensitivity test(CD-DST)法を用いた抗癌剤感受性試験による化学療法選択を試みた.6例の局所再発ならびに遠隔転移巣をもつ口腔癌患者に対して,CD-DST法による感受性試験の結果を踏まえた化学療法を行った.感受性試験の結果は,1例で評価不能,1例で検索した抗癌剤に感受性なしと判定され,この2例に関しては緩和療法のみを施行した.感受性のある薬剤が見いだされた4例に対しては,感受性試験に基づいた化学療法を施行した.重篤な有害事象はなく,生存期間の中央値は10.9ヵ月であった.CD-DST法による感受性試験に基づく化学療法は,治療法の選択において重要な情報を提供するものと考えられた(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE  

DOI： 10.1016/j.bjoms.2005.03.010

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Blocking angiogenesis may enhance conventional anticancer treatments such as radiation therapy. In this study, we examined the effects of the angiogenesis inhibitor TNP-470 on human OSCC cell lines HSC2 and KB, with combining radiation therapy in the nude mouse. We evaluated cell-induced neovascularization with dorsal air sac assay, and selected two cells (HSC2: low, KB: high) with different level of cell-induced angiogenesis. The angiogenesis inhibitor TNP-470 was given 30 mg/kg s.c. daily on day 1-5, and irradiation, 8 Gy x 1, was administered on day 1 each week for 3 weeks. Significant inhibition of tumor growth relative to untreated controls was achieved in KB cells showing high induced angiogenesis with both TNP-470 (P &lt; 0.01) and radiation (P &lt; 0.01) and combining TNP-470 and radiation (P &lt; 0.01). We saw little effect of TNP-470 either alone or in addition to the effect of radiation on the HSC2 cells showing low induced angiogenesis.
These results suggested that TNP-470 significantly enhanced the effect of radiation on the cells with high neovascularization. These findings indicated that individual evaluation of each tumor neovascularization potential will be important before deciding the anti-angiogenesis treatment. (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.oraloncology.2005.06.010

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Language：Japanese  

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Language：Japanese   Publisher：Japanese Society of Oral and Maxillofacial Surgeons  

We report on a patient who had tongue cancer with neck metastasis. The left common carotid artery was resected and replaced with an artificial vessel. A 49-year-old man was referred to our hospital because of an ulcer arising at the left side of the tongue. After 4 years of observation, the patient underwent a partial glossectomy because of malignant transformation. One year 6 months subsequently, the patient was readmitted because of metastasis to the left middle internal jugular lymph nodes. The neck metastasis surrounded the carotid artery and invaded its wall. In collaboration with vascular surgeons, an extended neck dissection was performed, and a segment of the common carotid artery was resected. A vascular prosthesis was used for reconstruction.&lt;BR&gt;Although this radical operation might not markedly increase the long-term cure rate, it may improve the quality of life and achieve loco-regional control of disease. This procedure should therefore be positively considered in selected patients with advanced neck metastasis.

DOI： 10.5794/jjoms.51.368

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE  

We report a case of diffuse sclerosing osteomyelitis of the mandible responded to alendronate, after a poor response to intravenous antibiotics, antibiotic irrigation-perfusion, and decortication. The patient was given an intravenous infusion of 10 mg of alendronate. Pain resolved within 24 h. There were no severe adverse events. Increased uptake of Tc-99m in the mandible almost completely disappeared 3 months after treatment.

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Language：Japanese   Publisher：Japanese Society of Oral and Maxillofacial Surgeons  

We encountered a patient in whom remitting seronegative symmetrical synovitis with pitting edema (RS3PE) developed after treatment with UFT. A 64-year-old man who had cervical and lung metastases of unknown origin was treated with docetaxel hydrate, cisplatin, and 5-fluorouracil. Subsequently, the patient received UFT at a dose of 300 mg/day. Shortly after starting treatment with UFT, symmetrical pitting edema developed in the dorsum of the hands and feet. Since the results of immunological examination were consistently negative for rheumatoid factor, the patient was given a diagnosis of RS3PE. The symptoms of RS3PE markedly improved after the withdrawal of UFT and the start of steroid therapy. The findings suggested that UFT may be related to the development of RS3PE.

DOI： 10.5794/jjoms.51.148

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本頭頸部癌学会  

Attempts were made to detect micrometastasis in N0 neck of oral cancer patients using sentinel lymph node (SN) biopsy (SNB). We previously described our approach to identify SN using a radioisotope (99mTc-Tin colloid) -guided and dye-guided method. Micrometastases were detected by means of serial sections and real-time PCR based on SCC antigen mRNA. In this study, we evaluated the radiolocalization of SN and identification of metastatic lymph node in N0 oral cancer patients. The positive rate of metastatic lymph node in N0 oral cancer was 35% and the diagnostic sensitivity of SNB was 95%. The SNB detected subclinical metastases in 4 of 10 N0 patients with tongue cancer. Moreover, in 3 of these 4 cases, all metastatic lymph nodes consisted with SNs. Postoperative cervical metastasis was observed in a patient whose SNB was negative. While more experience is needed, we believe the SN concept for tongue cancer is established, and practical application in clinical settings is anticipated. © 2005, Japan Society for Head and Neck Cancer. All rights reserved.

DOI： 10.5981/jjhnc.31.79

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Head and Neck Cancer  

Attempts were made to detect micrometastasis in N0 neck of oral cancer patients using sentinel lymph node (SN) biopsy (SNB). We previously described our approach to identify SN using a radioisotope (99mTc-Tin colloid) -guided and dye-guided method. Micrometastases were detected by means of serial sections and real-time PCR based on SCC antigen mRNA. In this study, we evaluated the radiolocalization of SN and identification of metastatic lymph node in N0 oral cancer patients. The positive rate of metastatic lymph node in N0 oral cancer was 35% and the diagnostic sensitivity of SNB was 95%. The SNB detected subclinical metastases in 4 of 10 N0 patients with tongue cancer. Moreover, in 3 of these 4 cases, all metastatic lymph nodes consisted with SNs. Postoperative cervical metastasis was observed in a patient whose SNB was negative. While more experience is needed, we believe the SN concept for tongue cancer is established, and practical application in clinical settings is anticipated. © 2005, Japan Society for Head and Neck Cancer. All rights reserved.

DOI： 10.5981/jjhnc.31.79

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Aims/hypothesis. It has previously been hypothesised that highly differentiated endocrine cells do not proliferate or regenerate. However, recent studies have revealed that cyclin-dependent kinase 4 (CDK4) is necessary for the proliferation of pancreatic islet beta cells. The aim of this study was to determine whether activation of CDK4 can potentially be used as a radical treatment for diabetes without malignant transformation.
Methods. We generated transgenic mice expressing mutant CDK4 under the control of the insulin promoter to examine the effect of activated CDK4 overexpression in the postnatal development of pancreatic islets.
Results. In the transgenic mice, total CDK4 protein expression was increased by up to 5-fold, with a concomitant increase in CDK4 activity indicated by the detection of phosphorylated Rb protein in pancreatic islets. Histopathologically, many cells tested positive for proliferating cell nuclear antigen, and pancreatic islets displayed hyperplasia due to the extreme proliferation of beta cells containing a large number of insulin granules. Pancreatic islet alpha, delta and PP cells did not increase. Over an 18-month observation period, the transgenic mice did not develop insulinoma. Levels of expression of GLUT1 and c-myc were comparable to those in the littermates of the transgenic mice. GLUT2 expression was identified in the pancreatic islets of transgenic mice. No significant differences in telomerase activities were detected between transgenic mice and their littermates. Transgenic mice were superior to their littermates in terms of glucose tolerance and insulin secretion in response to the intraperitoneal injection of glucose, and hypoglycaemia was not observed.
Conclusions/interpretation. Activated CDK4 stimulates postnatal pancreatic beta cell proliferation, during which the highly differentiated phenotypes of pancreatic islet beta cells are preserved without malignant transformation.

DOI： 10.1007/s00125-004-1522-4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE  

Sentinel node navigation surgery (SNNS) has received considerable attention for its role in deciding whether to perform neck dissection in patients with early oral cancer. However, diagnostic accuracy and its intraoperative availability of results remain important concerns. First, we shortened the examination time required for genetic diagnosis. Second, we assessed the quality of the extracted mRNA. Third, 10 patients with early NO oral cancer underwent SNNS, using our new technique for genetic diagnosis to determine whether neck dissection was required. The examination time of our one-step reverse-transcriptase polymerase chain reaction method using a minicolumn and LightCycler was successfully shortened to 2 h, permitting intraoperative genetic diagnosis. The extracted mRNA was of high quality. Six sentinel nodes in four patients were diagnosed to be metastatic on genetic diagnosis; these patients underwent neck dissection. The other six patients avoided unnecessary surgery. We conclude that intraoperative genetic diagnosis of micrometastasis holds promise of being a sensitive method that can be used to support SNNS.

DOI： 10.1016/j.ijom.2004.01.009

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Language：Japanese   Publisher：愛媛医学会  

単純性骨嚢胞4例(14歳女性,33歳男性,40歳女性,14歳男性)に対し,多血小板血漿(PRP)の応用を試みた.PRPの作製については,採取した患者血液(男性60ml,女性55ml)にクエン酸抗凝固剤7mlを混和し,遠心分離することでPRPを抽出した.いずれも単純性骨嚢胞を摘出後,PRP填入術を施行した.その結果,若年者の2例では術後早期に骨添加が確認でき,非常に良好な経過を示した.また,再発あるいは増大傾向を示した他の2例でも術後早期に骨添加を認め,術後長期の経過観察においても再発あるいは増大傾向を示さなかった

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Language：Japanese   Publisher：愛媛医学会  

症例1(17歳男性).患者は下顎左側中切歯部から右側第1大臼歯部の歯原性角化嚢胞に対する嚢胞摘出,開窓療法後であった.症例2(41歳男性).患者は左下顎第2大臼歯部の顎骨中心性癌に対する下顎骨区域切除術,右上頸部郭清術,血管柄付き腓骨皮弁移植による再建術後であった.症例3(25歳女性).患者は右下顎犬歯部から下顎枝部のエナメル上皮腫に対する下顎骨区域切除,遊離腸骨移植による再建術後であった.症例4(48歳男性).上顎左側埋伏犬歯部の上顎癌に対する上顎骨部分切除,左上頸部郭清,血管柄付き前腕・腓骨複合皮弁による再建術後であった.それぞれ症例1,2,3に対しては可撤式ブリッジ,症例4に対してはオーバーデンチャーによるインプラント補綴を行った.その結果,口腔機能をはじめ審美性の改善が得られた

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Language：Japanese   Publisher：愛媛医学会  

味覚障害患者24例(男性14例,女性10例)について臨床的検討を行った.その結果,年齢は12〜85歳(平均62.1歳)であった.全身合併症は17例で認め,うち循環器系疾患が8例と最も多かった.味覚異常と共に他の愁訴を併せ持つ患者は約7割で,その症状の殆どは口腔乾燥と舌痛であった.味覚低下を訴えた85.7%では電気味覚検査で味覚閾値の上昇が確認された.全口腔法による味質認知検査では,認知閾値の異常は39.1%で認めたが,患者の自覚的な訴えと検査結果が一致したものは味覚過敏を訴えた2例のみであった.原因別分類ではカンジダ症や舌痛症などの口腔疾患性と唾液分泌障害によるものが合せて8例と約1/3を占めた.治療は主にビタミンB製剤や唾液分泌促進剤,鉄剤の投与を行ったが,治療効果の乏しい20例には漢方投与を行い,うち13例で症状の改善を認めた

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Language：Japanese   Publisher：愛媛医学会  

症例1(57歳男性),症例2(73歳女性).いずれも両側下顎歯肉・口腔底癌に対する腫瘍切除術,両側全頸部郭清術,大胸筋皮弁・金属プレートによる再建術,喉頭挙上術後に嚥下機能障害が出現した.反復唾液嚥下テストではいずれも30秒間に1回の嚥下運動が観察されたが,水飲みテストでは飲水が不可能であった.嚥下造影検査では,舌運動性の低下による口腔機能障害と喉頭挙上不良が観察され,誤嚥が認められた.そこで,それぞれ術後2ヵ月,3ヵ月にPAPを装着し,実際に食物を用いた直接訓練を行った結果,嚥下機能の改善が得られた

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Language：Japanese   Publisher：(NPO)日本顎変形症学会  

39歳男.左側下顎骨の過成長に起因する顔面非対称であった.患者は矯正治療を希望せず,手術による審美的改善のみを強く希望したためWalkerの方法に準じた下顎下縁切除術を施行し,良好な結果を得た.手術に際して3D-CTデータをもとに作成した光造形3次元実体モデルは下顎管の位置の確認や骨削除範囲の決定に有用であった

DOI： 10.5927/jjjd1991.14.131

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Language：Japanese   Publisher：愛媛医学会  

86歳女.T2N0M0の硬口蓋癌と診断された.術前の触診,ならびに画像診断では,上顎洞内への腫瘍の浸潤,両側所属リンパ節転移,遠隔転移を思わせる所見は認められなかった.しかし,センチネルリンパ節(SLN)生検術を施行したところ,対側の頸部リンパ節転移を検出した.SLN生検はN0口腔癌患者の極小転移や治療に大変有用であると思われた

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Language：Japanese   Publisher：(株)癌と化学療法社  

76歳女.頸部リンパ節転移を伴う右側上顎癌に対して,CDDP及びTS-1を併用した術前化学放射線療法を行い,組織学的に腫瘍細胞の消失を認めた.CDDP,TS-1の投与と合計40Gyの放射線照射を併用し,投与中にはgrade 2の骨髄抑制,血小板減少,口内炎を認めた.触診及び画像診断上腫瘍は縮小し,PRと効果判定した.手術標本中には生細胞の残存を認めなかった.CDDP,TS-1の併用は口腔癌治療に有用であり,本症例のように術前化学放射線療法を行うことは手術時の安全域の設定や術後QOLの確保にとっても治療効果の高い方法であると考えられた

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Language：Japanese   Publisher：特定非営利活動法人 日本顎変形症学会  

We report a case of facial asymmetry treated by Walker&#039;s mandibuloplasty. This method has advantages of no orthodontic therapy and a shorter treatment period. In this case, Walker&#039;s mandibuloplasty was consistent with the patient&#039;s requests, and was useful to improve the facial asymmetry. Additionally, we used a three-dimensional model for preoperativediagnosis. Since this model showed an outline of the mandibular canal, the inferior alveolar nerve was safely moved and injury to it avoided. The model also helped to determine the resecting volume of the enlarged mandible before surgery.

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Language：Japanese   Publisher：(株)癌と化学療法社  

術前化学療法を行った口腔扁平上皮癌一次症例6例を対象に,術前治療にTXT,CDDP同時併用療法を行い,成績について報告した.臨床的効果はCR0例,PR5例,NC1例で,奏効率は83.3%であった.組織学的効果はグレードIIAが2例,グレードIIBが2例,グレードIIIが2例で奏効率は66.7%であった.最も多かった副作用は口内炎で6例すべてに認め白血球減少と脱毛を4例に,悪心・嘔吐を3例に認めた.また,食事摂取が困難となるグレード3以上の重篤な副作用は4例で認めた

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE CANCER ASSOC  

DNA-PK is a nuclear protein with serine/threonine kinase activity and forms a complex consisting of the DNA-PKcs and a heterodimer of Ku70 and Ku80 proteins. Recent laboratory experiments have demonstrated that the DNA-PK complex formation is one of the major pathways by which mammalian cells respond to DNA double-strand breaks induced by ionizing radiation. In this study, we evaluated the relationship between expression levels of DNA-PKcs, Ku70 and Ku80 proteins and radiation sensitivity in oral squamous cell carcinoma (OSCC) cell lines and in OSCC patients treated with preoperative radiation therapy. The OSCC cell lines greatly differed in their response to irradiation, as assessed by a standard colony formation assay. However, the expression levels of the DNA-PK complex proteins were all similar, and there was no association between the magnitude of their expression and the tumor radiation sensitivity. Expression of DNA-PK complex proteins increased after radiation treatment, and the increased values correlated with the tumor radiation resistance. Expression of DNA-PKcs and Ku70 after irradiation was increased in the surviving cells of OSCC tissues irradiated preoperatively. These results suggest that up-regulation of DNA-PK complex protein, especially DNA-PKcs, after radiation treatment correlates to radiation resistance. DNA-PKcs might be a molecular target for a novel radiation sensitization therapy of OSCC.

DOI： 10.1111/j.1349-7006.2003.tb01372.x

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Language：Japanese   Publisher：(一社)日本歯科薬物療法学会  

急性歯性感染症(歯周組織炎群,歯冠周囲炎群,顎炎群)83例(男35例・女48例,19〜87歳)を対象に,アジスロマイシン(AZM)の有効性について検討し,アンケート調査により,患者の使用感について調査した.対象症例83例(男35例・女48例,19〜87歳)における臨床効果は著効34例(41%),有効40例(48.2%),無効9例(10.8%)で,有効率は89.2%であった.薬を飲んだ効果は,はい72例(86.7%)で,症状の軽快を自覚した時期は内服2〜4日目で79.1%を占めた.1日1回3日間の飲み方については34例が簡便と答えて最も多く,特に問題なしがこれに次いだ.また,内服の満足度は86.6%(71例)で,今までの内服抗生剤との比較では,AZMの方がよいと答えた患者が60例(72.3%),変わらない20例(24.1%),今まで薬の方がよい3例(3.6%)であった

DOI： 10.11263/jsotp1982.22.76

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Vesnarinone has been shown to be a unique anti-proliferating, differentiation-inducing and apoptosis-inducing drug against several human malignancies, including leukemia and several solid tumors. Furthermore, vesnarinone potentiates the effect of conventional cytotoxic chemotherapy or radiation therapy. Combination of differentiation-inducing therapy by vesnarinone with conventional chemotherapy or radiation therapy might be second- or third-line therapy in patients with advanced cancer. Analysis of the molecular mechanisms of the tumor differentiation therapy by vesnarinone might provide selective and targeted molecules for novel tumor dormancy therapy.

DOI： 10.1097/01.cad.0000078735.65608.bf

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

TSC-22 gene was composed of three exons and its length was approximately 5.5 kb including 2.9 kb promoter region. The transcription starting site was located at 7 and 29 bp downstream from TATA box. Promoter analysis revealed that 2146 bp of TSC-22 promoter was activated by several differentiation inducing drugs. Although originally TSC-22 was isolated as a TGF-beta-inducible gene, TSC-22 promoter was not activated by the enhanced TGF-beta signaling. We found 3 copies of the Shaw-Kamens sequence (AUUUA) in the human TSC-22 mRNA 3'-UTR and identified three proteins (40, 20, and 15 kDa) which bound to this. Only the 40 kDa protein-RNA complex was decreased by treatment with TGF-beta1. Moreover, the TSC-22 mRNA 3'-UTR destabilized the heterologous luciferase mRNA, but the destabilization was recovered with TGF-beta1. These observations suggest that up-regulation of TSC-22 mRNA by TGF-beta1 is achieved by mRNA stabilization, but not by transcriptional activation. (C) 2003 Elsevier Science (USA). All rights reserved.

DOI： 10.1016/S0006-291X(03)00854-4

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Language：Japanese   Publisher：Japanese Society of Oral and Maxillofacial Surgeons  

Sentinel lymph node biopsy (SLB) is a rational method to avoid unnecessary neck dissection in patients with clinical N 0 oral cancer. At our department, dye-guided SLB has beencarried out since 2000. Since March 2002, we combined dye-guided and radioisotope (RI)-guided techniques.We describe the introduction and present status of this new technique.&lt;BR&gt;When adopting this RI technique, we encountered difficulties in understanding and cooperation by related personnel, including the nurses of the operating room. The problems pointed out focused on exposure of operators, nurses, and anesthesiologists to radioactivity, custody and disposition of radioactive waste, and radioactive contamination of operative and anesthetic instruments. We estimated that the average radiation dose to which the operators were exposed was 3.8 μSv. Radiation exposureof the nurses and anesthetists was negligible. The average radioactivity of the operation wastes was 1.3μSv/hr, and that of the operation instruments was 0.3 μSv/hr. These results indicate no problematicradioactive contamination, and we believe that this procedure causes no radiological damage to clinicalcoworkers. At present, we carry out combined dye-guided and RI-guided SLB with the cooperation of relatedpersonnel, including the nurses of the operation room.

DOI： 10.5794/jjoms.49.257

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Previous studies have shown that low levels of p27(KIP1), an inhibitor of G1 cyclin-dependent kinases (CDK), are associated with high aggressiveness and poor prognosis in a variety of cancers. Decreased levels of p27(KIP1) are caused, at least in part, by an acceleration of degradation with Skp2 (S-phase kinase-associated protein 2) and Jab1 (Jun activation domain-binding protein 1). This investigation was undertaken to examine whether the Skp2 and Jab1 expression is correlated with p27(KIP1) protein levels, and how it is clinically relevant in oral squamous cell carcinoma (OSCC). The correlations between p27(KIP1) and Skp2, and p27(KIP1) and Jab1 expression were evaluated by Western blot analysis. Immunohistochemical analysis was done in 75 cases of OSCC. A strongly significant inverse correlation was found between levels of p27(KIP1) and Skp2, and p27(KIP1) and Jab1 ( p &lt; 0.0001). Thus, decreased levels of p27(KIP1) were associated with strongly increased levels of Skp2 and Jab1, whereas high levels of p27(KIP1) coincided with low levels of Skp2 and Jab1. Reductions of p27(KIP1) expression and overexpression of Skp2 and Jab1 were significantly associated with cervical lymph node metastasis and poor prognosis. Overexpression of Skp2 and Jab1 is associated with the reduction of p27(KIP1) expression, and may have a role in the progression of OSCC. Copyright (C) 2003 S. Karger AG, Basel.

DOI： 10.1159/000074649

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Language：Japanese   Publisher：日本歯科薬物療法学会  

The efficacy of azithromycin as a chemoprophylactic agent for acute dental infection was assessed, and a questionnaire survey about the impression of azithromycin was conducted. METHODS: Eighty-three patients were given 500 mg of azithromycin for three days. Seven days after the onset of the treatment, we evaluated the clinical symptoms and collected the questionnaires. RESULTS: Clinical efficacy was observed in 89.2% of the patients, and that by questionnaire was 86.7%. Diarrhea as a side effect was seen in two patients. In the questionnaire, 79% of patients noted its effect from the second to fourth day after the medication. Although half of the patients did not care about the convenience, of taking the medication once a day, which is one of the advantages of azithromycin, most of the patients were satisfied with its efficacy.&lt;BR&gt;Furthermore, 72.3% of patients considered azithromycin to be significantly more acceptable compared with other antibiotics. CONCLUSION : Azithromycin is a useful therapeutic regimen for the treatment of acute dental infections.

DOI： 10.11263/jsotp1982.22.76

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Language：Japanese   Publisher：(一社)日本痛風・核酸代謝学会  

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DOI： 10.1038/sj.bjc.6600592

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PROFESSOR D A SPANDIDOS  

It is important to examine the abnormality of the entire p53 tumor suppressor pathway in head and neck cancer. We examined the mRNA expressions of p53 regulatory factors, p33ING1 and p14ARF, and a p53-target gene, p21WAF1 in head and neck cancer, Nine of 14 benign pleomorphic adenomas (PAs) and 7 of 8 malignant salivary gland tumors (MSGTs) expressed p33ING1 mRNA. Thirteen of 14 PAs expressed p14ARF mRNA, however, only I of 8 MSGTs expressed p14ARF mRNA. Eight of 14 PAs and 7 of 8 MSGTs expressed p21WAF1 mRNA. In salivary gland tumors, there was clear correlation between the expression of p33ING1 and p21WAF1 (p&lt;0.0001, r(2)=0.53). However, there was no correlation between the expression of p14ARF and p21WAF1 (p=0.6543, r(2)=0.009). Twenty-six of 28 oral squamous cell carcinomas (SCCs) expressed p33ING1 mRNA. Nineteen of 28 oral SCCs expressed p14ARF mRNA. All of the oral SCCs expressed p21WAF1 mRNA. In oral SCCs, the expressions of both p33ING1 (p=0.009, (r(2)=0.181) and p14ARF(p=0.0009, r(2)=0.271) correlated with the expression of p21WAF1. Interestingly, 24 of 26 oral SCCs (92%) showed either abnormality of p53 itself or loss of expression of p53 regulatory factors, p33ING or p14ARF. These results suggest that head and neck cancer often involve the dysfunction of p53 tumor suppressor pathway.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

We transfected a salivary gland cancer cell line, TYS, with three different forms of TSC-22 (transforming growth factor-beta-stimulated clone-22) gene: full-length TSC-22 (TSC-22FL) containing nuclear export signal, TSC-box and leucine zipper, truncated TSC-22 (TSC-22LZ) containing only TSC-box and leucine zipper, and truncated TSC-22 with nuclear localization signal (NLS-TSC-22LZ). High expression of TSC-22FL in the cytoplasm markedly enhanced the radiation-sensitivity of TYS cells, while, moderate expression of TSC-22FL marginally affected the radiation-sensitivity. TSC-22LZ, which was expressed in the cytoplasm and the nucleus, enhanced the radiation-sensitivity of TYS cells irrespective to its expression level. N-LS-TSC-22LZ, which was expressed only in the nucleus, marginally affected the radiation-sensitivity of the cells even at high expression level. Interestingly, cytoplasmic TSC-22 translocates to nucleus concomitant with radiation-induced apoptosis. These results suggest that cytoplasmic localization of TSC-22 and translocation of TSC-22 from cytoplasm to nucleus is important for regulating the cell death signal after irradiation-induced DNA damage. (C) 2002 Elsevier Science (USA).

DOI： 10.1006/bbrc.2002.6776

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PROFESSOR D A SPANDIDOS  

Several investigators have demonstrated that TGF-beta stimulated clone-22 (TSC-22) regulates cell growth and differentiation, and cell death. TSC-22 is a putative transcriptional regulator containing a leucine zipper-like structure and a nuclear export signal. We previously showed the cytoplasmic localization of TSC-22 and the nuclear translocation of TSC-22 concomitant with induction of apoptosis in salivary gland cancer cells. In the present study, we attempted to identify the active domain of TSC-22 protein that regulated the biological functions of TSC-22. We constructed three mammalian expression vectors, which could produce full length TSC-22 only in cytoplasm, the leucine zipper structure of TSC-22 in both cytoplasm and nucleus, and the leucine zipper structure only in nucleus. Then, we transfected a salivary gland cancer cell line, HSG with these expression vectors, and investigated the growth profile of the transfectants. None of the TSC-22 constructs inhibited the monolayer growth and the anchorage-dependent colony formation of HSG cells. However, the leucine zipper structure of TSC-22 markedly inhibited the anchorage-independent colony formation of HSG cells (p&lt;0.001; one way ANOVA). Full length TSC-22 also suppressed the anchorage-independent colony formation of HSG cells, although the effect of full length TSC-22 was much lower than those of the leucine zipper constructs. These observations suggest that the leucine zipper structure in TSC-22 protein is an active domain that negatively regulates the growth of salivary gland cancer cells.

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DOI： 10.3892/ijo.19.5.953

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-LISS  

We examined the role of the hepatocyte growth factor (HCF)/c-met system on invasion and metastasis of oral squamous cell carcinoma (SCC) cells. In monolayer culture, exogenous HCF marginally affected the growth of oral SCC cells (BHY, HN, IH) and human gingival epithelial cells (CE), In type I collagen matrix, however, HGF significantly enhanced the invasive growth of the cancer cells (p &lt; 0.05), We detected the expression of c-met (HGF receptor) mRNA in all of the cancer cells, but nor in human gingival fibroblasts (GF), Oral SCC cells did not secret HCF protein into the medium, but GF secreted a large amount of HGF protein (15 ng/ml), Furthermore, HCF markedly enhanced the migration of cancer cells in a Transwell invasion chamber. Then, we examined the serum levels of HGF in oral SCC patients, or HGF concentrations in oral cancer tissues. Serum levels of HCF in the patients were significantly higher than those in healthy volunteers (p &lt; 0.05), After initial treatment, all of the tumor-free survivors showed a marked decline in the serum HCF levels. Furthermore, HGF concentrations in metastatic cancer tissues were significantly higher than those of nonmetastatic cancer tissues and normal gingiva (p &lt; 0.01). These results suggest that HGF plays an important role in invasion and metastasis of oral SCC cells as a paracrine factor, and an elevated HCF level in the cancer tissue can be a predictive marker for metastasis formation in patients with oral SCC. (C) 2001 Wiley-Liss, Inc.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE  

Retinoids inhibit the proliferation of several types of tumour cells, and are used for patients with several malignant tumours. In this study, we examined the effect of retinoic acids (RAs) on the invasive potentials of the oral squamous cell carcinoma (SCC) cells, BHY and HNt. BHY cells expressed all of retinoid nuclear receptors (RAR alpha, beta, gamma, and RXR alpha) and cytoplasmic retinoic acid binding proteins (CRABP1 and CRABP2). HNt cells lacked the expression of RAR beta, but expressed other nuclear receptors and CRABPs. All-trans retinoic acid (ATRA) and 13-cis retinoic acid (13-cisRA) (10(-6) and 10(-7) M) inhibited the growth of the cells, but low-dose ATRA and 13-cisRA (10(-8) M) marginally affected the growth of the cells. Surprisingly. low-dose RAs enhanced the activity of tissue-type plasminogen activator (tPA), and activated pro-matrix metalloproteinases (proMMP2 and proMMP9). Activation of proMMP2 and proMMP9 was inhibited by aprotinin, a serine-proteinase, tPA inhibitor. Furthermore, low-dose RAs enhanced the in vitro invasiveness of BHY cells. These results indicate that low-dose RAs enhances the in vitro invasiveness of oral SCC cells via an activation of proMMP2 and proMMP9 probably mediated by the induction of tPA. (C) 2001 Cancer Research Campaign http://www.bjcancer.com.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC  

We examined the alteration of the subcellular localization of TSC-22 (TGF-beta -stimulated clone-22) after induction of apoptosis and the transcription-regulatory activity of TSC-22. In the living cells, TSC-22-green fluorescent protein (GFP) fusion protein was clearly localized to the cytoplasm, however, in the apoptotic cells, the TSC-22-GFP fusion protein was translocated from the cytoplasm to the nucleus. TSC-22 fused to GAL4-DNA binding domain (GAL4BD) did not show the transcriptional activity on the reporter genes in yeast and in HSG (salivary gland cancer cells) and Hela. However, in CHO cells, TSC-22-GAL4BD fusion protein strongly activated the reporter gene. The transcriptional activity of the leucine zipper structure of TSC-22 is greater than that of the full-length TSC-22. These findings suggest that after receiving the apoptotic stimuli, TSC-22 translocates from the cytoplasm to the nucleus and shows the transcription-regulatory activity. (C) 2000 Academic Press.

DOI： 10.1006/bbrc.2000.3840

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PROFESSOR D A SPANDIDOS  

We have isolated transforming growth factor-beta-stimulated clone-22 (TSC-22) cDNA as an anti-cancer drug-inducible gene in a human salivary gland cancer cell line, TYS. We have previously reported that TSC-22 negatively regulates the growth of TYS cells, and that overexpression of TSC-22 protein in TYS cells enhanced the in vitro chemosensitivity of the cells. In this study, we examined the in vivo chemosensitivity of TSC-22-expressing TYS cells. TSC-22-expressing TYS cells formed tumors in nude mice, but tumors formed by TSC-22-expressing TYS cells were significantly smaller than tumors formed by control cells (p&lt;0.001, one way ANOVA). Furthermore, intraperitoneal injection of 5-fluorouracil (5-FU) markedly inhibited the growth of the TSC-22-expressing TYS tumors, but did not affect the growth of control tumors. It was found by TUNEL assay that TSC-22-expressing TYS tumors were induced to undergo apoptosis by 5-FU treatment. These findings suggest that overexpression of TSC-22 protein in TYS cells enhances the in vivo chemosensitivity of the cells to 5-FU via induction of apoptosis.

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Language：Japanese   Publisher：四国歯学会  

主に癌細胞の細胞増殖抑制について,TSC-22の作用発現と細胞内局在部位との関連,あるいは細胞内での他の因子との相互作用についての解析を行った.その結果,TSC-22はN末に存在する核外移行シグナルを利用して積極的に細胞質に局在しており,通常は核内には存在しないことが明らかになった.通常は細胞質に存在し,何らかの刺激を受けたとき,核内に移行するのではないかと考えられた.酵母あるいは哺乳動物細胞においてTSC-22の転写活性化能を検索し,酵母Two Hybrid法あるいは哺乳動物培養細胞を用いた免疫沈降法により結合蛋白質の同定を試みた.その結果,TSC-22LZトランスフェクタントから,約50kDaのTSC-22結合蛋白質と考えられる蛋白質を検出した.TSC-22が何らかの修飾を受けてロイシンジッパーが他の分子と相互作用可能な立体構造を取った時にのみ,約50kDaの分子と結合できるようになるのではないかと考えられた

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

We have recently isolated TSC-22 (transforming growth factor-beta-stimulated clone-22) cDNA as an anticancer, drug-inducible (with vesnarinone) gene in a human salivary gland cancer cell line, TYS. We have also reported that TSC-22 negatively regulates the growth of TYS cells and that down-regulation of TSC-22 in TYS cells plays a major role in salivary gland tumorigenesis (Nakashiro et at, 1998). In this study, we transfected TYS cells with an expression Vector encoding the TSC-22-GFP (green fluorescent protein) fusion protein, and we established TSC-22-GFP-expressing TYS cell clones. Next, we examined (a) the subcellular localization of the fusion protein, (b) the sensitivity of the transfectants to several anticancer drugs (5-fluorouracil, cis-diaminedichoroplatinum, peplomycin), and (c) induction of apoptotic cell death in the transfectants by 5-fluorouracil treatment. The TSC-22-GFP fusion protein was clearly localized to the cytoplasm, but not to the nucleus. Over-expression of the TSC-22-GFP fusion protein did not affect cell growth, but significantly increased the sensitivity of the cells to the anticancer drugs (p &lt; 0.01; one-way ANOVA). Furthermore, over-expression of the TSC-22-GFP fusion protein markedly enhanced 5-fluorouracil-induced apoptosis. These findings suggest that over-expression of TSC-22-GFP protein in PIS cells enhances the chemosensitivity of the cells via induction of apoptosis.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PROFESSOR D A SPANDIDOS  

Epidermal growth factor (EGF) is a potent mitogen, and its action is mediated by MAP kinase (MAPK). Reportedly EGF activates STAT, induces the expression of p21(waf1), and subsequently inhibits the growth of several types of cancer cells. In this study, we used human bladder cancer cells (T24 and RT4), immortalized non-tumorigenic human urothelial cells (1T-1, 1T-2, and 1T-3), and epidermal carcinoma cells (A431). EGF inhibited the growth of T24 and A431, and stimulated the growth of 1T-1, 1T-3 and 1T-2, but did not affect the growth of RT4. EGF activated MAPK strongly in 1T-1, and slightly in A431, T24, 1T-2, and 1T-3 but marginally in RT4. We detected the activation of STAT in T24, 1T-3 and A431 after EGF treatment. EGF enhanced the expression of p21(waf1) mRNA in T24, 1T-2, 1T-3 and A431, and activated the p21(waf1) promoter in T24 cells. These results suggest that i) EGF inhibits the growth of T24 cells via induction of p21(waf1) mediated by STAT, and ii) the balance between the STAT-induced p21(waf1) and MAPK activities regulates the growth of human bladder cells after EGF treatment.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE  

We examined the expression of cytokeratin 20 (CK20) mRNA in the peripheral blood of oral squamous cell carcinoma (SCC) patients by reverse transcriptase polymerase chain reaction (RT-PCR). Eleven out of 12 oral SCC patients showed positive RT-PCR results. However, there is no clear relationship between the haematogenous CK20 mRNA and the metastasis. After initial treatment, all of the tumour-free survivors tested showed negative RT-PCR results. CK20 mRNA in peripheral blood can be used as a marker for tumour recurrence but not for metastasis in oral SCC patients.

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DOI： 10.1038/bjc.1998.11

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2016-1137

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2015-3793

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Language：Japanese   Publisher：日本口腔組織培養学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(NPO)日本口腔科学会  

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Language：Japanese   Publisher：日本口腔組織培養学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2012-1355

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Language：Japanese   Publisher：日本口腔組織培養学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：English   Publisher：日本癌学会  

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61歳女。ビスホスホネート関連顎骨壊死(BRONJ)の悪化にトシリズマブ(TCZ)が関与した機序として次のようなことが考えられた。1)メトトレキサート服用などにより免疫抑制下にある状態で、TCZの投与により骨代謝回転と血管新生が抑制された。2)TCZ投与により発熱やCRP産生が抑制され感染症の重症度が不顕化される"マスキング"によってBRONJの重篤化が引き起こされた。本症例への治療は、MTXおよびトシリズマブの投与を中止し、RAに対してはプレドニゾロン5mg/日およびセレコキシブ200mg/日を行ったところ、中止後、1ヵ月でリンパ節腫脹は著明に縮小し、口腔内病変も治癒が得られた。

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