記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recently, numerous tumor-suppressive microRNAs (TS-miRs) have been identified in human malignancies. Here, we attempted to identify novel TS-miRs in oral squamous cell carcinoma (OSCC). First, we transfected human OSCC cells individually with 968 synthetic miRs mimicking human mature miRs individually, and the growth of these cells was evaluated using the WST-8 assay. Five miR mimics significantly reduced the cell growth rate by less than 30%, and the miR-1289 mimic had the most potent growth inhibitory effect among these miRs. Subsequently, we assessed the in vivo growth-inhibitory effects of miR-1289 using a mouse model. The administration of the miR-1289 mimic-atelocollagen complex significantly reduced the size of subcutaneously xenografted human OSCC tumors. Next, we investigated the expression of miR-1289 in OSCC tissues using reverse transcription-quantitative PCR. The expression level of miR-1289 was significantly lower in OSCC tissues than in the adjacent normal oral mucosa. Furthermore, 15 genes were identified as target genes of miR-1289 via microarray and Ingenuity Pathway Analysis (IPA) microRNA target filtering. Among these genes, the knockdown of magnesium transporter 1 (MAGT1) resulted in the most remarkable cell growth inhibition in human OSCC cells. These results suggested that miR-1289 functions as a novel TS-miR in OSCC and may be a useful therapeutic tool for patients with OSCC.

DOI： 10.3390/cancers15164138

PubMed

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(一社)日本有病者歯科医療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

There are a few reports that focus on radiotherapy (RT) and cetuximab (CET) therapy exclusively for oral cancer. This retrospective study aimed to investigate the efficacy and safety of RT and CET therapy for locally advanced (LA) or recurrent/metastatic (R/M) oral squamous cell carcinoma (OSCC). Seventy-nine patients from 13 hospitals who underwent RT and CET therapy for LA or R/M OSCC between January 2013 and May 2015 were enrolled in the study. Response, overall survival (OS), disease-specific survival (DSS), and adverse events were investigated. The completion rate was 62/79 (78.5%). The response rates in patients with LA and R/M OSCC were 69% and 37.8%, respectively. When only completed cases were examined, the response rates were 72.2% and 62.9%, respectively. The 1- and 2-year OS were 51.5% and 27.8%, respectively (median, 14 months), for patients with LA OSCC, and 41.5% and 11.9% (median, 10 months) for patients with R/M OSCC. The 1- and 2-year DSS were 61.8% and 33.4%, respectively (median, 17 months), for patients with LA OSCC, and 76.6% and 20.4% (median, 12 months) for patients with R/M OSCC. The most common adverse event was oral mucositis (60.8%), followed by dermatitis, acneiform rash, and paronychia. The completion rate was 85.7% in LA patients and 70.3% in R/M patients. The most common reason for noncompletion was an inadequate radiation dose due to worsening general conditions in R/M patients. Although the standard treatment for LA or R/M oral cancer is concomitant RT with high-dose cisplatin (CCRT) and the efficacy of RT and CET therapy for oral cancer is not considered to be as high as that for other head and neck cancers, it was thought that RT and CET therapy could be possible treatments for patients who cannot use high-dose cisplatin.

DOI： 10.3390/ijerph20054545

PubMed

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Mutations in p53 are common in human oral squamous cell carcinoma (OSCC). However, in previous analyses, only detection of mutant p53 protein using immunohistochemistry or mutations in some exons have been examined. Full length mutant p53 protein in many cases shows a loss of tumor suppressor function, but in some cases possibly shows a gain of oncogenic function. In this study, we investigate relationships of outcomes with the mutational spectrum of p53 (missense and truncation mutations) in whole exon in OSCC. Specimens from biopsy or surgery (67 cases) were evaluated using next-generation sequencing for p53, and other oncogenic driver genes. The data were compared with overall survival (OS) and disease-free survival (DFS) using univariate and multivariate analyses. p53 mutations were detected in 54 patients (80.6%), 33 missense mutations and 24 truncation mutations. p53 mutations were common in the DNA-binding domain (43/52) and many were missense mutations (31/43). Mutations in other regions were mostly p53 truncation mutations. We detected some mutations in 6 oncogenic driver genes on 67 OSCC, 25 in NOTCH1, 14 in CDKN2A, 5 in PIK3CA, 3 in FBXW7, 3 in HRAS, and 1 in BRAF. However, there was no associations of the p53 mutational spectrum with mutations of oncogenic driver genes in OSCC. A comparison of cases with p53 mutations (missense or truncation) with wild-type p53 cases showed a significant difference in lymph node metastasis. DFS was significantly poorer in cases with p53 truncation mutations. Cases with p53 truncation mutations increased malignancy. In contrast, significant differences were not found between cases with p53 missense mutations and other mutations. The p53 missense mutation cases might include cases with mostly similar function to that of the wild-type, cases with loss of function, and cases with various degrees of gain of oncogenic function.

DOI： 10.1038/s41598-022-25744-8

PubMed

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記述言語：日本語   出版者・発行元：(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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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.ajoms.2021.10.011

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：日本語   出版者・発行元：(一社)日本有病者歯科医療学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本有病者歯科医療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Spandidos Publications  

DOI： 10.3892/ol.2021.12789

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Molecules that demonstrate a clear association with the aggressiveness of oral squamous cell carcinoma (OSCC) have not yet been identified. The current study hypothesized that tumor cells in OSCC have three different origins: Epithelial stem cells, oral tissue stem cells from the salivary gland and bone marrow (BM) stem cells. It was also hypothesized that carcinomas derived from less-differentiated stem cells have a greater malignancy. In the present study, sex chromosome analysis by fluorescence in situ hybridization and/or microdissection PCR was performed in patients with OSCC that developed after hematopoietic stem cell transplantation (HSCT) from the opposite sex. OSCC from 3 male patients among the 6 total transplanted patients were considered to originate from donor-derived BM cells. A total of 2/3 patients had distant metastasis, resulting in a poor prognosis. In a female patient with oral potentially malignant disorder who underwent HSCT, there were 10.7% Y-containing cells in epithelial cells, suggesting that some epithelial cells were from the donor. Subsequently, gene expression patterns in patients with possible BM stem cell-derived OSCC were compared with those in patients with normally developed OSCC by microarray analysis. A total of 3 patients with BM stem cell-derived OSCC exhibited a specific pattern of gene expression. Following cluster analysis by the probes identified on BM stem cell-derived OSCC, 2 patients with normally developed OSCC were included in the cluster of BM stem cell-derived OSCC. If the genes that could discriminate the origin of OSCC were identified, OSCCs were classified into the three aforementioned categories. If diagnosis can be performed based on the origin of the cancer cells, a more specific therapeutic strategy may be implemented to improve prognosis. This would be a paradigm shift in diagnostic and therapeutic strategies for OSCC.

DOI： 10.3892/ol.2021.12431

PubMed

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Administration of cetuximab (C-mab) in combination with paclitaxel (PTX) has been used for patients with head and neck squamous cell carcinoma (SCC) clinically. In this study, we attempted to clarify the molecular mechanisms of the enhancing anticancer effect of C-mab combined with PTX on oral SCC cells in vitro. We used two oral SCC cells (HSC4, OSC19) and A431 cells. PTX alone inhibited cell growth in all cells in a concentration-dependent manner. C-mab alone inhibited the growth of A431 and OSC19 cells at low concentrations, but inhibited the growth of HSC4 cells very weakly, even at high concentrations. A combined effect of the two drugs was moderate on A431 cells, but slight on HSC4 and OSC19 cells. A low concentration of PTX enhanced the antibody-dependent cellular cytotoxicity (ADCC) induced by C-mab in all of the cells tested. PTX slightly enhanced the anticancer effect of C-mab in this ADCC model on A431 and HSC4 cells, and markedly enhanced the anticancer effect of C-mab on OSC19 cells. These results indicated that PTX potentiated the anticancer effect of C-mab through enhancing the ADCC in oral SCC cells.

DOI： 10.3390/ijms21176292

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/cas.14359

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

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記述言語：日本語   出版者・発行元：日本心脈管作動物質学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Anticancer Research USA Inc.  

DOI： 10.21873/invivo.12159

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(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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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：日本語   出版者・発行元：(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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DOI： 10.1016/j.ijom.2019.01.027

PubMed

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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DOI： 10.3892/etm.2018.6869

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/ijc.31811

PubMed

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jop.12756

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer New York LLC  

Abstract: CXCL10, a CXC chemokine induced by interferon-gamma [IFN-γ], has been observed in a wide variety of chronic inflammatory disorders and autoimmune conditions. Although CXCL10 is known to be overexpressed in the salivary glands of individuals with primary Sjögren’s syndrome (pSS), it is unclear which cells produce CXCL10 under what types of stimulations. Here, we investigated the precise molecular mechanisms by which CXCL10 was produced in human salivary gland ductal (NS-SV-DC) and acinar (NS-SV-AC) cell lines. Our results demonstrated that NS-SV-DC cells produced higher levels of CXCL10 compared to NS-SV-AC cells. In addition, our findings demonstrated that the regulator of the enhancement of CXCL10 was different between NS-SV-DC and NS-SV-AC cells, i.e., interferon-gamma (IFN-γ) had more potential than interferon-alpha (IFN-α), tumor necrosis factor (TNF)-α, and interleukin (IL)1-β in the induction of CXCL10 production in NS-SV-DC cells, whereas TNF-α had potential to induce CXCL10 production in NS-SV-AC cells. A Western blot analysis demonstrated that IFN-γ enhanced the production of CXCL10 via both the JAK/STAT1 pathway and the NF-κB pathway in NS-SV-DC cells, whereas TNF-α enhanced the production of CXCL10 via the NF-κB pathway in NS-SV-AC cells. The results of study suggest that the CXCL10 overexpression in the salivary glands is caused mainly by IFN-γ-stimulated salivary gland ductal cells. The enhanced production of CXCL10 by IFN-γ from ductal cells may result in the inflammation of pSS lesions.

DOI： 10.1007/s10753-018-0764-0

Scopus

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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

Web of Science

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT INST ANTICANCER RESEARCH  

Background/Aim: 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. Patients and Methods: 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. Results: 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. Conclusion: Palonosetron is effective at preventing HEC-induced chemotherapy-induced nausea and vomiting (CINV) in oral cancer chemotherapeutic regimens in the acute and delayed phases.

DOI： 10.21873/anticanres.12165

Web of Science

PubMed

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記述言語：英語   出版者・発行元：NATURE PUBLISHING GROUP  

DOI： 10.1038/srep46915

Web of Science

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier Ltd  

Juvenile ossifying fibromas (JOFs) are rare fibro-osseous lesions. Conservative surgery, such as curettage and enucleation of the tumor, is the widely accepted therapeutic method
however, JOFs frequently recur after surgery. Here we report a case of a recurrent JOF, which had a hypervascular and aggressive phenotype. A 21-year-old woman presented with a painless, enlarged swelling at the left mandible. Clinical and biopsy findings indicated an ossifying fibroma. The initial tumor was treated via conservative curettage and recurred a year thereafter. The recurrent tumor was treated via segmental bone resection and recurred 2.5 years thereafter. With each recurrence, tumor cell proliferation and tumor hypervascularity increased. We describe the clinical and histological features of a twice-recurrent JOF. Our findings provide new insight into the mechanisms underlying recurrence and may facilitate the establishment of novel diagnostic methods for JOF.

DOI： 10.1016/j.ajoms.2017.07.002

Scopus

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Vascular endothelial cell growth factor receptor 2 (VEGFR2) is an essential receptor for the homeostasis of endothelial cells. In this study, we showed that NEDD8-conjugated Cullin3 (CUL3)-based ubiquitin E3 (UbE3) ligase plays a crucial role in VEGFR2 mRNA expression. Human umbilical vein endothelial cells treated with MLN4924, an inhibitor of NEDD8-activating enzyme, or with CUL3 siRNA drastically lost their response to VEGF due to the intense decrease in VEGFR2 expression. Moreover, speckle-type POZ protein (SPOP) and death-domain associated protein (DAXX) were involved in the CUL3 UbE3 ligase complex as a substrate adaptor and a substrate, respectively. Knockdown of SPOP and CUL3 led to the upregulation of DAXX protein and downregulation of VEGFR2 levels. These levels were inversely correlated with one another. In addition, simultaneous knockdown of SPOP and DAXX completely reversed the downregulation of VEGFR2 levels. Moreover, the CUL3-SPOP-DAXX axis had the same effects on NOTCH1, DLL4 and NRP1 expression. Taken together, these findings suggest that the CUL3SPOP-DAXX axis plays a very important role in endothelial cell function by targeting key angiogenic regulators.

DOI： 10.1038/srep42845

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

頸部リンパ節転移の有無は口腔癌の重要な予後因子である。cN0症例に対する治療方針としての、予防的頸部郭清術や経過観察についてはいまだ議論の余地があるのが現状である。センチネルリンパ節生検(SNB)は、様々な癌種において臨床応用がなされてきた。口腔癌におけるSNBの目的は、cN0症例に対し、頸部郭清術を行うか否かを決定することにある。しかしながら、口腔癌のSNBにおいては、以下の4つの問題点がある。すなわち、RIの使用、shine-through現象、潜在転移診断法とEBMの不足である。本稿では、口腔癌におけるセンチネルリンパ節生検の現状について解説する。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS LTD  

Objective Several studies have suggested that an elevated neutrophil-lymphocyte ratio (NLR) is associated with a poorer prognosis in patients with pancreatic cancer (PC). The correlations between the NLR and immunohistochemical (IHC) analysis with regard to the prognosis of patients with PC remain to be elucidated. By using IHC findings, we determined the value of the NLR as a prognostic factor in patients with PC. Material and methods We collected the clinico-pathological data of 28 consecutive patients who underwent surgical resection for PC between January 2008 and December 2012 at The Jikei University Kashiwa Hospital. We investigated whether the NLR and IHC results were related and ensured the consistency of the prognosis of patients with PC. Results The Kaplan-Meier curves for the disease-free survival (DFS) and the overall survival (OS) revealed that an NLR5 is an implicit factor for decreased DFS and OS in patients with PC (p=0.003, p<0.001, log-rank test). The density of CD163(+)macrophages and CD66b(+)neutrophils was significantly higher in the high NLR group; on the contrary, the density of CD20(+)lymphocytes was significantly higher in the low NLR group. Moreover, a Mann-Whitney U test showed that the NLR was significantly correlated with a high density of CD20(+)lymphocytes (p=0.031) and CD163(+)macrophages (p=0.023), while the NLR was not significantly correlated with CD66b(+)neutrophils (p=0.397). Conclusions Our results demonstrated the validity of the NLR by IHC analyses and we determined that a higher value of NLR is a trustworthy prognostic factor for patients with PC.

DOI： 10.3109/00365521.2015.1121515

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE  

Implant-retained overdentures are known to improve oral function, but the clinical impact on patients who have had mandibular resections is still debatable. We have treated 16 patients who had such resections for oral cancer and consequent loss of the alveolar ridge, with overdentures supported by osseointegrated implants and ball attachments. To quantify their functional improvement, we evaluated their maximum bite force and masticatory performance. Their function improved significantly, (from 77.5 N - 365 N, 371% increase in maximum bite force, p<0.001) and masticatory performance increased (from 2.5 - 7.7, 208%, p<0.0001) after the overdentures had been inserted. While individual changes in maximum bite force showed no significant correlation, those in masticatory performance correlated significantly, which suggests that the subjects with poor masticatory function are likely to benefit from retention of an implant. These results indicate that implant-retained overdentures are an effective way to rehabilitate patients after marginal mandibular resection. (C) 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bioms.201.5.11.017

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Epithelial cell plasticity is controlled by extracellular cues, but the underlying mechanisms remain to be fully understood. Epidermal growth factor (EGF) and amphiregulin (AREG) are high-and low-affinity ligands for EGF receptor (EGFR), respectively. EGFR signaling is known to promote epithelial-mesenchymal transition (EMT) by the activation of ERK and the induction of an EMT transcription factor, ZEB1. Here, we demonstrate that ligand-switching between EGF and AREG at equivalent molarity reversibly interconverts epithelial and mesenchymal-like states of EGFR signal-dependent mammary epithelial cells. The EGF- and AREG-cultured cells also differ in their epithelial characteristics, including the expression of cell surface markers, the mode of migration and the ability for acinus-formation. The ligand-switching between EGF and AREG temporally alters strength of the shared EGFR-ERK signaling. This alteration inverts relative expression levels of ZEB1 and its antagonizing microRNAs, miR-205 and miR-200c, those are critical determinants of the epithelial phenotype. Further, AREG-induced EGFR accumulation on the plasma membrane compensates for the weak association between AREG and EGFR. The EGFR dynamics enables AREG to support proliferation as efficiently as EGF at equivalent molarity and to maintain epithelial characteristics. Our findings reveal a role of EGFR ligands-generated signal strength in the regulation of mammary epithelial cell plasticity.

DOI： 10.1038/srep20209

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IMPACT JOURNALS LLC  

Molecularly targeted drugs are used in the treatment of a variety of malignant tumors, but this approach to developing novel therapies for oral squamous cell carcinoma (OSCC) has lagged behind the progress seen for other cancers. We have attempted to find appropriate molecular targets for OSCC and identified cell division cycle associated 5 (CDCA5) as a cancer-related gene which was overexpressed in all the human OSCC cells tested by microarray analysis. In this study, we investigated the expression and function of CDCA5 in OSCC. First, we confirmed that CDCA5 was overexpressed in 4 human OSCC cell lines by quantitative RT-PCR and Western blotting. We then tested the effect of synthetic small interfering RNAs specific for CDCA5 on the growth and invasion of human OSCC cells. Knockdown of CDCA5 markedly inhibited the growth of OSCC cells in vitro and in vivo. We also examined the expression of CDCA5 protein in 80 cases of OSCC immunohistochemically and found a significant association between CDCA5 expression levels and overall survival. These results suggest that CDCA5 functions as a critical gene supporting OSCC progression and that targeting CDCA5 may be a useful therapeutic strategy for OSCC.

DOI： 10.18632/oncotarget.6148

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IMPACT JOURNALS LLC  

Cervical lymph node metastasis is an important prognostic factor in oral squamous cell carcinoma (OSCC), but its accurate assessment after sentinel node biopsy or neck dissection is often limited to the histopathological examination of only one or two sections. Previous our study showed the usefulness of the reverse transcription loop-mediated isothermal amplification (RT-LAMP) targeting keratin 19 (KRT19) mRNA for the genetic detection of lymph node metastasis, but the sensitivity was insufficient. Here, we have attempted to identify novel molecular markers for OSCC cells in lymph nodes. We performed microarray analysis to identify genes overexpressed in 7 metastatic lymph nodes from OSCC patients, compared to 1 normal lymph node and 5 salivary glands from non-cancer patients. We then used real-time quantitative RT-PCR (qRT-PCR) and RT-LAMP to compare the expression of these genes in newly resected metastatic and normal lymph nodes. Of 4 genes identified by microarray analysis, annexin A8 (ANXA8) and desmoglein 3 mRNA were detected by qRT-PCR in metastatic lymph nodes but not in normal lymph nodes. Furthermore, ANXA8 mRNA expression was detected in all KRT19-negative metastatic lymph nodes. Both KRT19 and ANXA8 mRNA may be useful markers for detecting lymph node metastases in OSCC patients.

DOI： 10.18632/oncotarget.6639

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記述言語：日本語   出版者・発行元：(公社)日本生化学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE  

Oral squamous cell carcinoma (OSCC) frequently metastasizes to cervical lymph nodes, which is the most known prognostic factor. Screening methods to identify sentinel lymph nodes (SLNs) are therefore of great interest for the management of potential neck metastasis. The purpose of this study was to evaluate the clinical benefit of double SLN mapping with indocyanine green (ICG) and 99m-technetium-tin colloid (Tc-99m-tin colloid) for sentinel node navigation surgery (SNNS). Between 2007 and 2010, 16 patients diagnosed with OSCC were investigated by SLN biopsy using the double mapping method. Tc-99m-tin colloid was injected into the peri-tumoural region on the preoperative day, and ICG was administered intraoperatively in the same position to assist in detecting nodes during surgery. Based on the gamma-ray signal and near-infrared (NIR) fluorescence of ICG, SLNs were identified and thereafter assessed pathologically and genetically for cancer involvement. Radio-guided detection was successful for all patients. ICU mapping identified a relatively larger number of nodes, suggesting that several non-SLNs were potentially involved. The double mapping method assisted surgeons to explore SLNs. Since the ICG fluorescence was shielded by the subcutaneous fatty tissue and the muscle layer including platysma and sternocleidomastoid, it was necessary to retract the tissue away from nodes.

DOI： 10.1016/j.ijom.2015.05.008

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

In our previous study, ribonucleotide reductase M2 (RRM2) was identified as a cancer-related gene commonly overexpressed in human oral squamous cell carcinoma (OSCC) cell lines. Herein, we attempted to determine whether targeting RRM2 may be a plausible therapeutic approach for the treatment of patients with OSCC. First, we examined the expression levels of RRM2 in human OSCC cell lines and tissues. Overexpression of RRM2 in OSCC was confirmed by western blot analysis. Subsequently, we investigated the effects of a synthetic small interfering RNA specific for RRM2 and gemcitabine (GEM), an inhibitor of RRM2 enzymatic activity, on the growth of human OSCC cell lines and primary cultured cells. Targeting RRM2 by RNA interference almost completely suppressed the expression of RRM2 and markedly suppressed the growth of both types of cells by >54.8%. GEM also reduced the growth rate of these cells by >83.0%. Finally, we evaluated the antitumor effects of GEM, cisplatin (CDDP), 5-fluorouracil (5-FU), and docetaxel (DOC) against OSCC cells using the collagen gel droplet embedded culture drug sensitivity test. OSCC cells were more sensitive to GEM and DOC than to CDDP and 5-FU, regardless of the expression level of RRM2 mRNA. These results suggested that RRM2 supported the growth of human OSCC cells and that targeting of RRM2, e.g., via GEM treatment, may be a promising therapeutic strategy for OSCC.

DOI： 10.3892/ijo.2015.2912

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：E-CENTURY PUBLISHING CORP  

Peripheral ameloblastoma (PA), a rare and unusual variant of odontogenic tumors, comprises about 1% of all ameloblastomas. PA is an exophytic growth localized to the soft tissues overlying the tooth-bearing areas of the jaws, and the initial diagnosis is often fibrous epulis. PA with histologically low-grade malignant features is extremely rare. We report a case of peripheral ameloblastoma with histologically low-grade malignant features in a 69-year-old woman that presented with a hemorrhage from a tumor on the right buccal mucosa. The tumor was surgically removed by blunt dissection, with no evidence of recurrence after two years and six months. After the case presentation, microscopic and genetic findings are discussed.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Purpose: We investigated whether serum interleukin (IL)-8 reflects the tumor microenvironment and has prognostic value in patients with oral squamous cell carcinoma (OSCC).
Experimental Design: Fifty OSCC patients who received radical resection of their tumor(s) were enrolled. Preoperative sera were measured for IL-8 by ELISA. Expression of IL-8 and the infiltration of immune cells in tumor tissues were analyzed by an immunohistochemical staining of surgical specimens.
Results: We found that disease-free survival (DFS) was significantly longer in the Stage I/II OSCC patients with low serum IL-8 levels compared to those with high levels (p=0.001). The tumor expression of IL-8, i.e., IL-8(T) and the density of CD163-positive cells in the tumor invasive front, i.e., CD163(IF) were correlated with the serum IL-8 level (p=0.033 and p=0.038, respectively), and they were associated with poor clinical outcome (p=0.007 and p=0.002, respectively, in DFS) in all patients. A multivariate analysis revealed that N status, IL-8(T) and CD163(IF) significantly affected the DFS of the patients. Further analysis suggested that combination of N status with serum IL-8, IL-8(T) or CD163(IF) may be a new criterion for discriminating between OSCC patients at high and low risk for tumor relapse. Interestingly, the in vitro experiments demonstrated that IL-8 enhanced generation of CD163-positive M2 macrophages from peripheral blood monocytes, and that the cells produced IL-10.
Conclusions: These findings indicate that IL-8 may be involved in poor clinical outcomes via generation of CD163-positive M2 macrophages, and that these factors in addition to N status may have prognostic value in patients with resectable OSCSS.

DOI： 10.1371/journal.pone.0110378

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Background: Liver dysfunction and cirrhosis affect vasculature in several organ systems and cause impairment of organ functions, thereby increasing morbidity and mortality. Establishment of a mouse model of hepatopulmonary syndrome (HPS) would provide greater insights into the genetic basis of the disease. Our objectives were to establish a mouse model of lung injury after common bile duct ligation (CBDL) and to investigate pulmonary pathogenesis for application in future therapeutic approaches.
Methods: Eight-week-old Balb/c mice were subjected to CBDL. Immunohistochemical analyses and real-time quantitative reverse transcriptional polymerase chain reaction were performed on pulmonary tissues. The presence of HPS markers was detected by western blot and microarray analyses.
Results: We observed extensive proliferation of CD31-positive pulmonary vascular endothelial cells at 2 weeks after CBDL and identified 10 upregulated and 9 down-regulated proteins that were associated with angiogenesis. TNF-a and MMP-9 were highly expressed at 3 weeks after CBDL and were less expressed in the lungs of the control group.
Conclusions: We constructed a mouse lung injury model by using CBDL. Contrary to our expectation, lung pathology in our mouse model exhibited differences from that of rat models, and the mechanisms responsible for these differences are unknown. This phenomenon may be explained by contrasting processes related to TNF induction of angiogenic signaling pathways in the inflammatory phase. Thus, we suggest that our mouse model can be applied to pulmonary pathological analyses in the inflammatory phase, i.e., to systemic inflammatory response syndrome, acute lung injury, and multiple organ dysfunction syndrome.

DOI： 10.1371/journal.pone.0094550

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：日本がん免疫学会  

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記述言語：日本語   出版者・発行元：日本がん免疫学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NEOPLASIA PRESS  

Eighty-one patients with oral squamous cell carcinoma (OSCC) received oral fluoropyrimidine UFT and radiotherapy (RT) with or without an immunotherapeutic agent OK-432. Both overall survival and progression-free survival of patients who received RT + UFT + OK-432 were significantly longer than those of patients who received RT + UFT (P = .0075 and P = .0175, respectively). Clinical response was also more favorable in RT + UFT + OK-432 group than in RT + UFT group (P = .0066). Next, in vitro experiments were conducted to examine the effect of 5-fluorouracil (5-FU) and X-ray irradiation in OK-432-induced immunity. Human peripheral blood mononuclear cells stimulated with OK-432 produced helper T cell 1 (Th1)-type cytokines as well as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta), which are produced by Th2 and regulatory T cells (Tregs), respectively, and are inhibitory in antitumor immunity. OK-432-induced IL-10 and TGF-beta but not Th1 cytokines were significantly inhibited by 5-FU and/or X-ray. 5-FU and X-ray also inhibited the expression of mRNAs for GATA-3 and Foxp3, which are transcription factors for Th2 and Tregs, respectively, but not for T-bet, a transcription factor for Th1. In addition, 5-FU and X-ray decreased the expression of mRNAs for suppressor of cytokine signaling 1 (SOCS1) and SOCS3. Antisense oligonucleotides for SOCS1 and SOCS3 markedly reduced OK-432-induced IL-10 and TGF-beta. This is the first report clearly demonstrating that OK-432-based immunotherapy significantly enhanced the therapeutic effects of chemoradiotherapy in patients with OSCC as well as elucidating the mechanism of the synergistic effect of immunochemoradiotherapy in which 5-FU and radiation enhanced OK-432-induced Th1 response mediated by the inhibition of SOCS1 and SOCS3 gene expression.

DOI： 10.1593/neo.13488

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Objectives: Oncogene addiction has provided therapeutic opportunities in many human malignancies, but molecular targeted therapy for oral squamous cell carcinoma (OSCC) is not yet available. In this study, we attempted to identify an appropriate target molecule for treatment of patients with OSCC.
Materials and methods: Microarray analysis was performed to determine the gene expression profiles in nine human OSCC cell lines and a non-neoplastic keratinocyte cell line. The expression levels of Aurora kinase A (AURKA) mRNA and protein in human OSCC cells and tissues were examined. We investigated the effect of small interfering RNAs specific for AURKA (siAURKAs) and MLN8237, an AURKA selective inhibitor on the growth of OSCC cells in vitro and in vivo. We also analyzed clinical significance in AURKA mRNA expression levels in OSCC.
Results: AURKA was overexpressed in human OSCC cell lines and tissues. All siAURKAs almost completely suppressed the expression of AURKA protein, and significantly inhibited the growth of OSCC cells by 31-89%. MLN8237 also reduced the cellular growth rate by 38-74%. Both siAURKA and MLN8237 significantly reduced the size of subcutaneously xenografted OSCC tumors by 66% and 40%. Knockdown of AURKA expression and MLN8237 induced the growth inhibition of primary cultured cells established from patients' OSCC tumors. Furthermore, we found a significant association between AURKA mRNA expression levels and histological differentiation and lymph node metastasis.
Conclusions: AURKA plays a critical role in the growth of human OSCC cells and targeting AURKA may be a useful therapeutic strategy for OSCC. (C) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.oraloncology.2013.02.002

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NEOPLASIA PRESS  

Antitumor functions of the host immune system are frequently compromised in patients with malignancies. In the current study, we evaluated the relationship between expression ratio of mRNAs for the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax (the Bcl-2/Bax ratio) in peripheral blood mononuclear cells and clinical outcomes in patients with head and neck carcinomas. The overall survival (OS) time of patients with Bcl-2/Bax ratios >= 1.2 tended to be longer than that of patients with Bcl-2/Bax ratios < 1.2 but not significantly so (P = .084, n = 61). Disease-free survival (DFS) of patients with Bcl-2/Bax ratios = 1.2 was statistically significantly longer than that of patients with Bcl-2/Bax ratios < 1.2 (P = .001, n = 76). All of the patients whose Bcl-2/Bax ratio is = 2.0 were alive after 36 months and survived without any evidence of disease for 24 months (Bcl-2/Bax >= 2.0 versus Bcl-2/Bax < 2.0; P = .035, n = 61 inOS, P < .001, n = 76 in DFS, respectively). In 56 patients who received immunochemoradiotherapy using UFT and OK-432 in combination with radiotherapy, a statistically significant relationship between the Bcl-2/Bax ratio and the therapeutic effect estimated using Response Evaluation Criteria in Solid Tumors was observed, as well as a relation with interferon-gamma (IFN-gamma) induction in response to the therapy [P = .002 in complete response versus partial response + stable disease; P = .046 in IFN-gamma(+) versus IFN-gamma(-)]. Inaddition, there were significant correlations of the Bcl-2/Bax ratiowith both the absolute number of CD4(+) T cells and the rate of CD4+ T cell and natural killer cell activity. These findings strongly suggest that the balance of expression of Bcl-2 and Bax genes in circulating immune cells has a high prognostic value in head and neck cancer patients.

DOI： 10.1593/neo.121528

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Objectives: Lymph node stage is an important prognostic factor in head and neck squamous cell carcinoma (HNSCC). We previously reported the clinical usefulness of sentinel lymph node biopsy diagnosed by genetic analysis using quantitative RT-PCR. However, this method takes about 3 h. In this study, we attempted to develop a more efficient method for the intraoperative genetic detection of lymph node metastasis in HNSCC.
Materials and methods: A total of 312 lymph nodes (65 patients) were diagnosed by the one-step nucleic acid amplification (OSNA) method using GD-100. OSNA consists of a short homogenization step followed by amplification of cytokeratin 19 (CK19) mRNA directly from the lysate. Each lymph node was divided into two to diagnose metastasis. One half was used for the OSNA assay, and the other was subjected to semi-serial sectioning, sliced at 200-mu m intervals and examined by H&E and cytokeratin AE1/AE3 immunohistochemical staining. The accuracy of OSNA assay was evaluated based on histopathological diagnosis.
Results: Sixty-one of 312 lymph nodes were pathologically metastasis-positive. The overall concordance rate between the OSNA assay using breast cancer criteria and histopathology was 94.2%. The optimal cutoff for the copy number of CK19 mRNA in assessing lymph node metastasis of HNSCC was 300 copies/mu l, which had the highest diagnostic accuracy (95.2%). The OSNA assay can be completed within 30 min.
Conclusion: The OSNA assay, which shows high sensitivity and specificity, suggests the possibility to be used as a novel tool for the genetic detection of lymph node metastasis in HNSCC patients. (C) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.oraloncology.2012.03.026

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Toll-like receptor 4 (TLR4) plays a significant role in cancer therapy as receptors of bacteria-derived immunotherapeutic agents such as OK-432, a streptococcal immunotherapeutic agent. In addition, recent reports demonstrated that TLRs, including TLR4, are also expressed in cancer cells as well as in immunocompetent cells. It is a problem in cancer therapy that the immunoadjuvant may activate survival signals such as nuclear factor (NF)-kappa B or mitogen-activated protein kinases (MAPKs) in cancer cells via TLRs. In the current study, we investigated responsiveness of human head and neck cancer cell lines against TLR4 ligands, OK-PSA, an active component of OK-432, and a lipopolysaccharide (LPS).
Stimulation with LPS or OK-PSA resulted in the activation of NF-kappa B in these cell lines expressing TLR4 and MD-2 that is a significant coreceptor for TLR4 signaling. Interestingly, OK-PSA induced cell-growth inhibition, while LPS enhanced the proliferation of the cancer cells. OK-PSA induced NF-kappa B activation more slowly than that induced by LPS. In addition, phosphorylation of p38 MAPK by OK-PSA was only slight compared with that by LPS. OK-PSA also induced apoptosis of the cancer cells mediated by the activation of caspase 1, 3 and 8 in a p53-independent manner.
These findings strongly suggest that active components of OK-432 may elicit anti-cancer effects via enhancing host immunity as well as via directly inducing the growth inhibition and apoptosis of head and neck cancer cells through TLR4 signal. (c) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.oraloncology.2012.02.005

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Objective: To study vascular anatomy on oral cancer-draining lymph nodes before metastasis in mice.
Material and methods: Cell lines: highly lymph metastatic oral squamous cell carcinoma SASL1m and non-metastatic human adenoid cystic carcinoma ACC2. Bone marrow transplants and xenografts: Nude mice were lethally irradiated and transplanted with bone marrow cells from EGFP(+) mice. SASL1m or ACC2 cells were implanted in the tongue. Non-xenografted mice were used as controls. In addition, we injected conditioned medium from SASL1m or ACC2 in transplanted mice. Immunohistochemistry: Primary tumors and neck lymph nodes were resected and stained with anti-mouse Podoplanin and CD31. Images were visualized in a confocal microscope. Image analysis: Areas covered by EGFP, CD31 and Podoplanin were measured and compared statistically. Expression microarrays: Transcriptomic microarray analysis compared SASL1 to ACC2 cells. Interactomes were generated to reveal altered pathways.
Results: SASL1m cells induced the assemblage of blood vessels in cancer-free, tumor-draining lymph nodes. These blood vessels incorporated bone marrow-derived EGFP(+)CD31(+) cells. Notably, SASL1m-conditioned medium induced a similar reaction. Non-metastatic cells failed to produce any change. Microarray and pathway analyses revealed the upregulation of Transforming Growth Factor-beta, Lysyl Oxidase-like 2, Slit homolog 3 and Protease Serine 22. The upregulation of these genes was confirmed in xenografts.
Conclusions: This study suggests that a blood supply for new tumors is established in lymph nodes before metastasis. It also suggests that premetastatic vasculogenesis and primary tumor angiogenesis may be mediated by different mechanisms. (c) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.oraloncology.2012.02.007

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Although replication-competent oncolytic viral vectors have been developed to improve antitumor activity, the generation of high titers of neutralizing antibodies inhibits repetitive viral infection. Many studies have reported that oncolytic virus-infected carrier cells can overcome this viral induced immunogenicity. However, the effects of oncolytic virus-infected carrier cells in human oral squamous cell carcinoma (OSCC) have not yet been examined. In the present study, simulating the clinical trial, we examined the antitumor activity of carrier cells infected with oncolytic adenovirus AdE3-IAI.3B in human OSCC. IAI.3B was highly activated in OSCC cells but not in normal cells. AdE3-IAI.3B killed OSCC cells in vitro but not normal cells. AdE3-IAI.3B-infected A549 carrier cells eradicated OSCC GFP-SAS tumors in nude mice. Anti-adenovirus neutralizing antibodies completely blocked the antitumor effect of AdE3-IAI.3B but did not block that of carrier cells. After the induction of anti-adenoviral CTL responses by immunization of adenovirus, administration of carrier cells induced complete regression of murine squamous cell carcinoma SCC7 tumors. Adenovirus-GM-CSF augmented the antitumor effect of carrier cells. The IAI.3B-driven oncolytic adenovirus-infected carrier cell system might prove useful in the treatment of OSCC and clinical trials of it should be conducted in the near future.

DOI： 10.3892/or.2010.1130

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE  

Radiotherapy is commonly used to treat oral squamous cell carcinoma (OSCC), but its therapeutic effects are unpredictable. To determine which genes correlate with radiation resistance in oral cancer, the authors evaluated radiation sensitivity using a standard colony formation assay with a gene microarray system for seven OSCC cell lines. They found significant associations between dozens of gene-expression levels and radiation resistance of OSCC cell lines. Following analysis of the different radiosensitive cancer cell lines, the friend leukaemia insertion (Fli)-1 gene was selected as a prediction marker gene for OSCC radiotherapy resistance. Fli-1 expression was associated with radiation resistance in OSCC patients. These data help to predict the effects radiation therapy has on OSCC, in turn contributing to the development of alternative radiation therapies.

DOI： 10.1016/j.ijom.2010.02.027

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Spindle cell carcinoma is considered a subtype of squamous cell carcinoma. There is no effective chemotherapy for cases of recurrence after first-line treatment, and the prognosis is poor. The patient was an 85-year-old man with spindle cell carcinoma after irradiated squamous cell carcinoma of the left lower gingiva. Extended surgery was performed, but 1 month postoperatively recurrence in the contralateral lower lip, cervical lymph node metastasis, and liver metastasis were detected, and treatment with S-1 was started. After 1 month of treatment, the cervical lymph node metastasis had resolved, and the liver metastasis had regressed, but after 4 months of treatment new cervical lymph node metastasis, lung metastasis, and rapid enlargement of the liver metastasis were observed, and led to the patient's death. Treatment with S-1 alone had an adequate antitumor effect temporarily. Further chemotherapeutic trials including S-1 are recommended to treat spindle cell carcinoma. © 2010 Asian Association of Oral and Maxillofacial Surgeons.

DOI： 10.1016/j.ajoms.2010.03.002

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記述言語：日本語   出版者・発行元：(一社)日本歯科薬物療法学会  

口腔乾燥症、舌痛症、味覚異常に対してエコルデンタルハービィを臨床応用し、その有用性および使用時の副作用について検討した。口腔乾燥、舌の疼痛、味覚異常などを主訴に受診し、エコルデンタルハービィの継続的使用が可能な80例を対象とした。歯ブラシは水で濡らさずエコルデンタルハービィを適量とり毎食後3分以上使用させ、その間は他の歯磨剤の使用を控えるよう指示した。口腔乾燥症症例では、唾液分泌量の増加は認めず、口腔乾燥感など自覚症状や他覚症状の改善は認めなかった。舌痛症症例では、使用後2ヵ月目以降、有意な疼痛改善を認めた。味覚異常症例では、味覚閾値の低下や味覚症状の改善は認めなかった。

DOI： 10.11263/jsotp.29.83

CiNii Books

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

One of the most critical issues of cancer chemotherapy is to establish a method for predicting efficacy or toxicity of anti-cancer drugs for individual patients. To identify genes that correlate with chemosensitivity of oral cancer treatment, we performed cDNA microarray analysis of nine oral squamous cell carcinoma (OSCC) cell lines. We compared gene-expression profiling with the sensitivity of OSCC cell lines to five anti-cancer drugs (5-fluorouracil, cisplatin, docetaxel, mitomycin C and adriamycin), which were measured using the collagen gel droplet embedded culture-drug sensitivity test method. We found significant associations between dozens of gene-expression levels and chemosensitivity of OSCC cell lines. These data should prove useful in the identification of predictive drug sensitivity markers, which may eventually provide "personalized chemotherapy" for individual patients, as well as for the development of novel drugs against chemotherapeutic resistance. © 2010 Asian Association of Oral and Maxillofacial Surgeons.

DOI： 10.1016/j.ajoms.2009.05.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JOHN WILEY & SONS LTD  

Background The squamous cell carcinoma antigen (SCCA) serves as a serological marker for squamous cell carcinomas. Molecular cloning of the SCCA genomic region has revealed the presence of two tandemly arrayed genes: SCCA1 and SCCA2. SCCA1 gene is up-regulated in squamous cell carcinoma cells. We analyzed the proximal region of the SCCA1 promoter and the antitumor effect of oncolytic adenovirus driven by the SCCA1 promoter in squamous cell carcinoma cells.
Methods The SCCA1 promoter was analyzed by dual luciferase assay and substituted with the E1A promoter to construct the oncolytic adenovirus to determine the squamous cell carcinoma-specific cell lysis.
Results Deletion analysis of SCCA1 promoter identified a 175-bp core promoter region and an enhancer region at 525 to 475 bp upstream of the transcription start site. The transcriptional activity of the SCCA1 promoter was up-regulated in squamous cell carcinoma cells. Five tandem repeats of enhancer increased SCCA1 promoter activity by four-fold. Oncolytic adenovirus driven by this SCCA1 enhancer-promoter complex specifically killed squamous cell carcinoma cells in vitro and in vivo. A549 carrier cells infected with the oncolytic adenovirus induced complete regression of syngeneic squamous cell carcinoma cell tumor by overcoming immunogenicity and adenovirus-mGM-CSF augmented the antitumor effect of carrier cells.
Conclusions SCCA1 was up-regulated in squamous cell carcinoma cells and oncolytic adenovirus driven by SCCA1 promoter specifically killed these cells. These findings suggest that SCCA1 promoter is a potential target of gene therapy for squamous cell carcinoma. Copyright (C) 2010 John Wiley & Sons, Ltd.

DOI： 10.1002/jgm.1467

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Although signal transducer and activator of transcription 3 (Stat3) plays crucial roles in the determination of neural stem cell (NSC) fate, Stat3 has multiple roles in NSC function Moreover, Stat3 plays important roles in neuronal survival and tumorigenesis. To investigate the overall effects of Stat3 on NSC fate, NSC were isolated from Stat3(flox/flox) mouse embryos (E14-15d), in which both Stat3 alleles are flanked by LoxP sites Isolated NSC was inoculated with an adenovirus vector expressing Cre recombinase (Ad nCre) or a control adenovirus vector expressing beta-galactosidase (Ad.nLz). Three days later, quantitative real-time PCR (qPCR) analysis revealed that treatment with Ad.nCre eliminated sun 3 mRNA expression in NSC Promoter assay confirmed that overexpression of nCre inhibited transactivation of acute responsive element (APRE) and blocked Stat3 function in NSC Moreover, Western blot analysis and immunocytochemical analysis revealed that elimination of Stat3 in NSC promoted neurogenesis and inhibited astrogliogenesis In addition, we investigated the effects of Stat3 elimination in NSC on the mRNA expression of Notch family members and bHLH factors Consequently, qPCR analysis showed that elimination of Stat3 in NSC promoted neurogenesis and inhibited astrogliogenesis through down-regulation of notch!, notch2 and hes5, but not hes1 mRNA expression (C) 2010 Elsevier Inc All rights reserved

DOI： 10.1016/j.bbrc.2010.03.092

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE  

Metastasis of malignant tumors to the oral cavity is rare. The authors report a case of thyroid carcinoma with mandibular osteoblastic metastasis. An 83-year-old female presented with lower jaw swelling and pain. An elastic hard subcutaneous mass was observed in the median mandible. X-ray images confirmed a tumor lesion with periosteal reaction spreading radially from the mandible. A biopsy revealed nests of large, polygonal tumor cells growing in a supporting fibrovascular framework. The patient's anamnesis included thyroid carcinoma with lung metastasis, 2 years ago, treated by total enucleation of the thyroid and excision of the superior lobe of the left lung. Biopsy, primary and metastatic tumor samples all tested positive for thyroglobulin, suggesting a thyroid follicular epithelial origin. Mandibular metastasis of poorly differentiated carcinoma of the thyroid gland was diagnosed. Consent for further treatment was not obtained. The patient died 1 year and 7 months later.

DOI： 10.1016/j.ijom.2009.10.014

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

68歳男。当科受診の約1年前から左側上顎歯肉の腫瘤を自覚していたが、増大するたびに患者自身が手指にて除去しながら経過観察していた。1ヵ月前、同部から出血があり近医受診した。同院での生検で腎細胞癌からの転移性腫瘍が疑われ、全身検索の結果、左腎に原発腫瘍が確認され、頸部リンパ節・肺・脳に転移が認められた。このため口腔内腫瘍の精査を含めた加療目的で当科に紹介された。口腔内所見として左側上顎小臼歯部を中心に42×53mm大で表面が壊死層に覆われた外向性・弾性軟・易出血性の腫瘤を認め、免疫組織化学検査やマイクロアレイ解析により腎細胞癌からの転移と診断した。原発巣と肺・脳転移巣は比較的緩慢な経過をたどったが、口腔内腫瘍は急速な増大を示した。全身状態から根治的治療は困難と判断し、口腔内腫瘍に対しては姑息的な腫瘍減量術を繰り返し行った。これによりQOLの維持が図れたが、次第に全身状態が悪化し、約半年の経過で死亡した。

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記述言語：日本語   出版者・発行元：(一社)日本泌尿器科学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

71歳男。関節リウマチで60歳時より治療開始し、メソトレキセート(MTX)の土、日毎週投与を11年間継続中である。右側上顎歯肉部の疼痛と歯肉退縮を認めていたが経過をみていた。その後、疼痛が増強し、内服加療を行っていたが症状が改善しないため、精査、加療目的に紹介にて初診となった。パノラマX線写真では歯の残存部では歯周病によると思われる歯槽骨の軽度吸収を認めた。臨床診断は右側上顎歯肉悪性腫瘍であった。右側上顎の潰瘍性病変部より生検を行った。MTXの服用は中止を指示し、1週の休薬により腫瘍周囲硬結はほぼ消失した。MTX中止後も病変が消退しないことから、MTX関連B細胞非ホジキンリンパ腫が考えられた。リツキシマブの投与を入院下に行い、肉眼的に腫瘍は消失した。現在、治療後約32ヵ月経過しているが再発なく経過良好である。病理組織学的診断はMTX関連B細胞非ホジキンリンパ腫(びまん性大細胞型)であった。

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

27歳女。左側顎下部の腫脹を主訴とした。オトガイ部の後退感に対してシリコンプロテーゼを用いたオトガイ形成術を受けており、受診時には左側顎下部皮膚に軽度圧痛を伴う比較的境界明瞭な発赤、腫脹を認めたが、排膿はみられなかった。CTにて同部位の皮下に内部均一な構造物(最大径30mm)が確認され、左側顎下部プロテーゼ迷入としてシリコンプロテーゼ除去術を行った。術後1年経過現在、経過は良好で目立った後遺障害はなく、オトガイ部の後退感については矯正専門医との共診にて外科的矯正治療を計画中である。本症例ではプロテーゼの挿入に起因すると考えられるオトガイ部の骨吸収が顕著であり、骨吸収がプロテーゼの不安定性を招き、オトガイ下部から顎下部に迷入したと考えられた。

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Hypoxia promotes the invasive and metastatic potential of tumour cells. A recent study has shown that the activation of the chemokine receptor CXCR4 by lack of oxygen in breast cancer is HIF-1-dependent. We have previously demonstrated that CXCR4 signalling is involved in the establishment of lymph node metastasis in oral squamous cell carcinoma (OSCC). In this study, we investigated a correlation between CXCR4 and HIF-1 alpha expression in OSCC. Immunohistochemistry showed that CXCR4 was expressed in 20 of 85 OSCC tissues, while HIF-1 alpha was expressed in 51 of 85 samples. There was a significant correlation between the expression of CXCR4 and HIF-1 alpha. In human OSCC cells, hypoxia markedly enhanced the expression of both HIF-1 alpha and CXCR4. Furthermore. synthetic small interfering RNA specific for HIF-1 alpha significantly suppressed the expression of this protein, and also attenuated the induction of CXCR4 expression under hypoxic conditions. These results indicated that HIF-1 alpha regulated hypoxia-induced CXCR4 expression in OSCC.

DOI： 10.3892/or_00000275

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

近年、FDG PET-CTは悪性腫瘍の原発、所属リンパ節および遠隔転移の精査に広く用いられている。今回、われわれは口腔扁平上皮癌cN0症例におけるFDG PET-CTおよびセンチネルリンパ節生検の意義について検討した。対象は、従来の画像診断にて頸部リンパ節転移を認めず、同時にFDG PET-CTによる精査を行った口腔扁平上皮癌23症例、計43個のセンチネルリンパ節とした。センチネルリンパ節を同定、摘出したのちに病理組織学的に転移の有無を評価した。その結果、43個のリンパ節のうち転移陽性リンパ節は4症例4個で、そのうちFDG PET-CTで診断可能であったものは1症例1個のみであった。以上の結果より、口腔扁平上皮癌の頸部リンパ節転移の評価において従来の画像診断に加え、FDG PET-CTを用いてもその診断精度には限界が認められるため、センチネルリンパ節生検の併用が必要であることが示唆された。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：COMPANY OF BIOLOGISTS LTD  

Amphiregulin (AR), a member of the EGF family, is synthesized as a type I transmembrane protein precursor (proAR) and expressed on the cell surface. Shedding of proAR yields a transmembrane-cytoplasmic fragment (AR-CTF), as well as a soluble AR. Here we demonstrate that the proAR-shedding stimuli trigger endocytosis of both AR-CTF and un-shed proAR. ProAR translocates from the plasma membrane to the inner nuclear membrane, whereas AR-CTF is translocated to the lysosome via retrograde membrane trafficking. Nuclear envelope localization of proAR involves truncation of the C-terminus, which subsequently activates the ER-retrieval signal. The truncated form of proAR interacts with A-type lamin and is retained at the inner nuclear membrane. Heterochromatin formation is then induced and global transcription is transiently suppressed. This study gives new insight into epigenetic chromatin organization in mammalian cells: a plasma-membrane-anchored growth factor is targeted to the inner nuclear membrane where it participates in dynamic chromatin organization and control of transcription.

DOI： 10.1242/jcs.031443

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

Constitutive activation of signal transducer and activator of transcription 3 (Stat3) has been observed in many human malignancies. Using the sequence-specific RNA interference (RNAi) method to switch off Stat3 expression, it may be possible to arrest cancer growth. In this study, we aimed to identify the most effective sequence of a synthetic small interfering RNA (siRNA) specific for Stat3 (Stat3-siRNA) and the effect of Stat3 suppression on the growth of oral squamous cell carcinoma cells. Ten designed siRNAs with known sequences were screened for the best RNAi effect at the working concentrations of 1 and 10 nM. The range of reduction of Stat3 expression varied from 21 to 67% for 10 nM siRNAs, and from 13 to 73% for 1 nM siRNAs. Three out of the 10 screened siRNAs reduced Stat3 expression to lower levels compared with the GFP-siRNA control. The interferon response of some siRNAs was observed at a concentration of 10 nM. However, at I nM, the mRNA levels of interferon response genes (OAS1, OAS2, MX1 and ISFG3 gamma) remained unchanged. The growth of GFP-SAS, HSC-3, HSC-4 and KB cells was strongly inhibited by the use of three effective Stat3-siRNAs in comparison with other Stat3-siRNAs and GFP-siRNA. Moreover, the mRNA levels of genes for which transcription is activated by Stat3 were markedly suppressed. These results suggest that targeting Stat3 using, siRNA may constitute a useful approach for the treatment of oral squamous cell carcinoma.

DOI： 10.3892/or_00000085

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：SPRINGER  

While the significance of large cervical node metastases in patients with head and neck squamous carcinomas is well established, the import of a finding of regional nodal micrometastases (where a micrometastasis is defined as a metastatic deposit greater than 0.2 mm and not greater than 2.0 mm in greatest dimension) or isolated tumor cells in those patients is less clearly understood. Some earlier investigators have suggested that finding micrometastases does not have an impact on prognosis; some later investigators, however, have taken issue with this position, arguing that finding either micrometastases or isolated tumor cells might portend a poorer prognosis for head and neck cancer patients. At this juncture, it is difficult to advance a single recommendation for handling a finding of micrometastases or isolated tumor cells. It would be helpful if two courses of action were followed: first, while the detection of micrometastases and isolated tumor cells remains an investigatory practice, data should be collected and analyzed with an eye to discerning whether such findings are indeed of significance to the individual head and neck cancer patient. Second, rigorous definitions of micrometastases and isolated tumor cells (such as the definitions suggested here) should be developed and widely employed so as to permit ready comparison between the results as they are reported by different investigators.

DOI： 10.1007/s00405-008-0715-8

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：英語   出版者・発行元：JOHN WILEY & SONS INC  

Background. Recently, attention has been focused on molecular targeted cancer therapy in various tumors. Although there is no single consistent molecular target specific for oral squamous cell carcinoma (OSCC) and salivary gland cancer (SGC), there are a number of promising candidate proteins. The aim of this review is to introduce the basic evidences to support the molecular targeting for OSCC and SGC.
Methods. We focused on the 4 molecules, epidermal growth factor receptor (EGFR), cyclooxygenase-2 (COX-2), peroxisome proliferator-activated receptor gamma (PPAR gamma), and progesterone receptor, that are, respectively, associated with the proliferation and the differentiation of OSCC and SGC.
Results. Gefitinib ("Iressa," ZD1839), a small molecule EGFR tyrosine kinase inhibitor, can inhibit the proliferation of OSCC cell lines in a dose- and time-dependent manner and lead to cell cycle arrest with accumulation of cells in the G1 phase, and a decrease of cells in S phase, The agent suppressed tumor metastasis in the animal model. Furthermore, a cooperative anti proliferative effect was obtained when cancer cells were treated with radiation followed by gefitinib, While radiation alone did not significantly affect p38 mitogen-activated protein kinase and MAP kinase kinase (MEK)1/2 autophosphorylation, the combination of gefitinib and radiation completely inhibited the downstream signaling of EGFR. Gefitinib enhanced tumor radioresponsiveness by multiple mechanisms, including the growth inhibition and effects on DNA repair after exposure to radiation. Next, the level of COX-2 expression correlated inversely with increased tumor radiation sensitivity. Treatment with celecoxib, a COX-2 selective inhibitor, enhanced the radioresponsiveness of HSC-2 cells, which constitutively expressed COX-2. Another promising molecular target is the PPAR gamma, which is a member of the nuclear receptor superfamily of ligand-activated transcription factors. Recent studies have demonstrated that PPAR-gamma ligands induce cellular differentiation and inhibit cell growth in carcinomas of various types. These data suggest that synthetic PPAR-gamma ligands may be useful for molecular targeting of oral cancer. Finally, the possibility of using molecular targeted therapy directed at hormone receptors in the treatment of advanced SGCs was described.
Conclusion. The basic data strongly suggested the possibility of tumor suppression by targeting these molecules. Studies of different targeted agents alone or with more conventional treatment modalities are needed to fully determine what role the targeted therapy will play in the management of patients with OSCC and SGC. (C) 2008 Wiley Periodicals, Inc.

DOI： 10.1002/hed.20830

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

The expression of hepatocyte growth factor (HGF) and c-Met is associated with tumor progression in many human malignancies. A recent study demonstrated HGF and c-Met expression in human salivary gland cancer tissues. Here, we investigated the role of the HGF/c-Met system in the invasive growth of two human salivary gland cancer cell lines: green fluorescent protein-adenoid cystic carcinoma 2 (GFP-ACC2) and GFP-ACCM. HGF enhanced the invasive growth of the two cell lines by activating PI3K/Akt signaling. All Akt isoforms (Akt1, Akt2, and Akt3) were detected in both cell types by Western blot analysis. Knockdown of any of the Akt isoforms using isoform-specific synthetic small-interfering RNAs largely abrogated the invasive growth induced by HGF. Our findings suggest that all of the Akt isoforms are required for the HGF-stimulated invasive growth of human salivary gland cancer cells, and that targeting a single Akt isoform could be effective in treating salivary gland cancers. (c) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2008.03.042

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

症例は認知症で他院精神科に入院中の77歳男性で、義歯の一部が口底部に迷入しているのを看護師に発見された。同院歯科で除去を試みたが、維持装置部が深く迷入しており、意識下での除去は危険と判断され当院に救急搬送された。下顎左4〜7部に部分床義歯を使用しており、左側口底部に義歯の双子鉤部とリンガルバー部が迷入していた。X線検査により義歯が下顎骨縁を超えて深部に迷入していることが明らかになり、CT検査で左側傍咽頭部に義歯の金属部分が迷入していることが判明した。このことから、局所麻酔下の摘出では体動の制御や出血時の対応に苦慮することが予想され、全身麻酔下に緊急摘出手術を施行した。ペアンを用いて周囲の剥離を行い、義歯に絹糸を掛けて牽引しながら更に周囲の剥離を行った。双子鉤部は舌筋層に陥入しており、この部分では特に慎重に剥離を行った。双子鉤周囲の剥離が終わると出血はほとんどなくなり、義歯は容易に摘出された。術後経過良好で、翌日に紹介元へ転院となった。

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

症例は85歳と55歳の男性で、いずれもTNM分類N0の上顎悪性黒色腫で、センチネルリンパ節生検での迅速病理検査で転移陽性と診断されたため患側全頸部郭清術を施行した。2例とも術後の最終的な病理組織検査でセンチネルリンパ節以外のリンパ節に1個の転移巣を認めた。

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recently, FDG PET-CT has been widely applied to examine the primary region of malignant tumor and metastasis to the lymph nodes or distant organs. Here, we investigated the usefulness of FDG PET-CT and sentinel lymph node biopsy in patients with cN0 oral squamous cell carcinoma. The scope of this study was 43 sentinel lymph nodes from 23 patients with oral squamous cell carcinoma in whom lymph node metastasis was not detected by traditional imaging, and who were examined by FDG PET-CT. After the sentinel lymph nodes were identified and resected, we evaluated the presence of metastasis in them histopathologically. As a result, in 43 lymph nodes, we detected metastases in 4 lymph nodes from 4 patients, but only 1 lymph node from 1 patient was detected by FDG PET-CT. These results suggest that FDG PET-CT and traditional imaging may have limited accuracy for diagnosing cervical lymph node metastasis, and that sentinel lymph node biopsy is also necessary. © 2008, Japan Society for Head and Neck Cancer. All rights reserved.

DOI： 10.5981/jjhnc.34.513

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

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記述言語：英語   出版者・発行元：西日本泌尿器科学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Homozygous deletions (HD) provide an important resource for identifying the location of candidate tumor suppressor genes. To identify the tumor suppressor gene in oral cancer, we employed high-resolution comparative genomic hybridization (CGH)-array analysis. We identified a homozygous loss of FAT ( 4q35), a new member of the human cadherin superfamily, from genome-wide screening of copy number alterations in one primary oral cancer. This result was evaluated by genomic polymerase chain reaction in 13 oral cancer cell lines and 20 primary oral cancers and Southern blot in the cell lines. We found frequent exonic HD of FAT in the cell lines (3/13, 23%) and in primary oral cancers (16/20, 80%). FAT expression was absent in these cell lines. Homozygous deletion hot spots were observed in exon 1 (9/20, 45%) and exon 4 (7/20, 35%). Moreover, loss of gene expression was identified in other types of squamous cell carcinoma. The methylation status of the FAT CpG island in squamous cell carcinomas correlated negatively with its expression. Our results identify mutations in FAT as an important factor in the development of oral cancer and indicate the importance of FATs function in some squamous cell carcinomas.

DOI： 10.1038/sj.onc.1210330

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

A p53 functional analysis system, which can identify the types of abnormality of p53, such as loss of function, dominant negative function, or gain of oncogenic function, is now required. In this study, we examined the functional diversity of several mutations of p53 derived from human head and neck cancer cells. The entire open reading frame of p53 cDNA was subcloned into a mammalian expression vector, pEGFP-C3, and genetic mutations were determined. Then, intracellular localization and transcriptional activity of the tumor-derived p53 proteins were examined in Saos-2 cells. A mutant-p53 (Glu17Lys, His193Leu) or a truncated p53 (Delta 121) did not activate the reporters containing p53 responsive elements from p21waf1, BAX, MDM2, p53AIP1, and PUMA genes at all. However, a mutant-p53 (Asn30Ser) showed the transcriptional activity on all of the reporters as wild-type p53 did. On the other hand, a mutant-p53 (Asp281His) activated the p21waf1 promoter strongly and the MDM2 promoter faintly, but did not activate the BAX promoter. Interestingly, this mutant-p53 prevented Saos-2 cells from undergoing apoptosis after treatment with a DNA damaging agent, adriamycin. This mutant-p53 induced cell cycle arrest but not apoptosis. Furthermore, another mutant-p53 (Glu17Lys, His193Leu) also prevented the cells from undergoing apoptosis after DNA damage probably in a transcription-independent manner. These results suggest that some cancer cells may contain the oncogenic mutation of the p53 gene, and the oncogenic p53 protein prevents cancer cells from undergoing apoptosis after DNA damage. Detailed information for mutated p53 gene in cancer cells might provide useful suggestions for the therapeutic strategy.

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

91歳男。患者は右側舌縁部の疼痛を主訴とした。所見では表面粗造で45×35mmの周囲に硬結を伴う腫瘤が認められ、MRIのT1強調画像では境界明瞭な低信号領域がみられた。また、病理組織像ではクロマチンが粗大顆粒状に増加しており、好酸性の核小体明瞭な紡錘形の腫瘍細胞がシート状に増殖していた。以上より、本症例は右側舌癌と診断されたが、患者が手術療法を強く拒否したため、浅側頭動脈から逆行性に腫瘍栄養動脈にカテーテルを留置する超選択的動注化学療法と、放射線療法の同時併用が施行された。副作用軽減は放射線治療時にバイトブロックを咬合させることで放射線性口内炎の範囲を縮小でき、治療終了時まで経口摂取可能であった。また、抗悪性腫瘍剤として比較的腎毒性の少ないカルボプラチンを投与量に留意しながら用いた。その結果、重篤な副作用もなく治療を完遂され、最終的には手術は回避できなかったが、予定した術式に比較して切除範囲は明らかに縮小された。現在までQOLを低下させるような術後機能障害は認められていない。

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

70歳女。患者は開口障害を主訴とした。パノラマX線では右側上顎第二大臼歯根尖部に境界明瞭な透過像が認められ、CTでは右側側咽頭隙から翼突下顎隙にかけて、右側上顎第二大臼歯根尖部と連続する内部不均一な径40mmの腫瘤性病変を認めた。根尖性歯周炎、右側翼突下顎隙膿瘍と診断し、抗菌薬による治療を開始したが、微熱が継続し、白血球数、CRPの上昇を認めた。初診時に軽度胸痛があったことからX線撮影を行なったところ、両側肺野に結節性陰影が数個確認された。またCTでは一部結節の空洞化を認め、結節に肺動脈が連続する像を認めた。白血球数、呼吸数が増加しており、感染による全身性炎症反応症候群と考え、CT、臨床所見から敗血症性肺塞栓症と診断された。以後、抗菌薬の継続により炎症状態の改善、胸部症状の消退、開口量の増加を認めて、原因歯の抜歯を行った。その結果、本症例は根尖性歯周炎による菌塊が塞栓子となり、肺塞栓症を引き起こしたものと考えられた。

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記述言語：日本語   出版者・発行元：愛媛医学会  

口腔癌の新規癌抑制遺伝子の同定のためのより効率的なスクリーニング法の探索を目的に、2種類のgenome microarrayを用いてヒト口腔扁平上皮癌由来細胞株HSC3の全ゲノム遺伝子解析を行った。BACアレイ解析とSNPアレイ解析を行った結果、前者では欠失領域上にいくつか既知の癌抑制遺伝子があり、1p36には非遺伝性腫瘍で不活化されるp73が、18q21.1には大腸癌で不活化するSMAD2、SMAD4があった。SNPアレイではBACアレイより多くの欠失領域を検出し、9ヶ所に両者一致した欠失領域を認めた。解像度の点でSNPアレイの方が優れていたが、SNPプローブの大きさは25bpと小さく、ハイブリダイゼーションの安定性はBACアレイに劣ると考えられた。

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記述言語：日本語   出版者・発行元：一般社団法人 日本泌尿器科学会  

DOI： 10.5980/jpnjurol.98.321_2

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Clinical studies with prostate cancer tissue indicate that alterations in androgen receptor (AR) or c-Met overexpression are associated with androgen-independent progression. We investigated the interaction between AR and c-Met signaling in human prostate cancer cells. Androgen withdrawal or AR-specific small interfering RNA significantly reduced the growth rate while each maneuver induced the expression of c-Met. Knockdown of both AR and c-Met expression markedly inhibited the cell growth. Furthermore, microarray analysis indicated that the activation of c-Met down-regulated the expression of DNA repair-related genes including 8-oxoguanine DNA glycosylase. Exogenous hepatocyte growth factor also induced the production of intracellular reactive oxygen species and resulted in the accumulation of DNA damages. These results suggested that the activation of c-Met signaling may lead to induction of spontaneous mutations or genomic instability, which may lead to the progression of androgen-independent state. Thus, c-Met signaling is utilized for survival and growth under the androgen-depleted condition. (c) 2006 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2006.07.040

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Hypoxia increases the invasive and metastatic potential of tumor cells. Increased expression of c-Met/hepatocyte growth factor (HGF)-receptor protein in response to hypoxia in thyroid papillary carcinomas is hypoxia-inducible factor-1 (HIF-1) dependent. Both HGF and c-Met are expressed in human salivary gland cancers. In the current study, we tested whether c-Met expression was regulated by hypoxia and HIF-1 alpha using two human salivary gland cancer cell lines: GFP-ACC2 and GFP-ACCM. Hypoxia enhanced the expression of HIF-1 alpha in both cell lines, whereas c-Met was markedly induced only in the GFP-ACCM cells, which have metastatic potential. In the latter, hypoxia also promoted HGF-induced invasiveness. Synthetic small-interfering RNA specific for HIF-1 alpha inhibited HIF-1 alpha expression in the GFP-ACCM cells, and also suppressed the increase in c-Met expression and HGF-induced invasiveness under hypoxic conditions. These results suggest that hypoxia activates the HGF/c-Met system via HIF-1 alpha in human salivary gland cancers and might be involved in their metastasis. (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.oraloncology.2005.10.016

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

BACKGROUND. Promyelocytic leukemia zinc finger (PLZF) protein, a transcriptional repressor and negative regulator of the cell cycle, has been characterized as a prostatic androgen-responsive gene. DU145 cells show androgen-independent growth and lack PLZF gene expression.METHODS. We analyzed PLZF-regulating genes by DNA microarray using DU145 cells infected with LacZ- or PLZF-carrying adenoviruses.RESULTS. DNA microarray revealed that Pbx1 is a prominent suppressed gene in PLZF-overexpressing DU145 cells. Androgen receptor (AR)-expressing DU145 cells recovered androgen-dependent PLZF expression and subsequent repression of Pbx1 expression. Immunoprecipitation of Pbx1 in DU145 cells revealed a Pbx1-HoxC8 heterocomplex. siRNAs for Pbx1 and HoxC8 knocked downexpression of each, and this suppressed androgenin-dependent cell growth. Double knockdown of both Pbx1 and HoxC8 suppressed cell growth much more significantly.CONCLUSIONS. Androgen-independent cell line DU145 cells lack PLZF gene expression, resulting in the upregulation of Pbx1 and HoxC8 expression. The Pbx1-HoxC8 heterocomplex may lead to androgen-independent growth in prostate cancer.

DOI： 10.1002/pros.20443

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(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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記述言語：日本語  

CiNii Books

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

ヒト全遺伝子型マイクロアレイを用いて,ヒト全遺伝子のうち最も有用性の高い腫瘍マーカーの同定を試みた.初回治療を行った口腔癌2例を対象とした.口腔癌患者由来の血液RNAより全遺伝子発現量を定量化した.比較対照として健常者血液を用いた.口腔扁平上皮癌症例では対照と比較して3倍以上の発現亢進を認めた遺伝子を197種類,唾液腺癌症例では152種類同定した.最も発現亢進を認めた遺伝子を各症例の個別腫瘍マーカーとした.術後,画像検査にて再発および転移が認められないことを確認したのち,再び血液RNAを用いて術前と同様の解析を行った.個別腫瘍マーカーは著明に低下し,正常化した.腫瘍マーカーの個別化が技術的に可能で,癌細胞存在診断において有用となる可能性が示唆された

DOI： 10.5981/jjhnc.31.493

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

49歳男.46歳時,右側甲状腺癌にて甲状腺右葉切除術を施行された.左側舌縁部に接触痛を認め,左側舌縁部の潰瘍で受診した.難治性口内炎の診断で,ステロイド軟膏の塗布などを行って,経過観察した.紅斑の一部に硬結を触知したため,癌化を疑い,摘除生検を行った.病理組織診断は中分化型扁平上皮癌であった.1年6ヵ月後,左側頸部に腫脹を認め,穿刺細胞診でClass V,扁平上皮癌と診断した.舌扁平上皮癌術後,左側頸部後発転移と診断した.術後は,抗凝血療法を行った.全身への微小転移を考慮し,多剤併用による術後化学療法を3クール施行した.病理組織学的診断は高分化型扁平上皮癌で,中心部に壊死を伴う腫瘍塊が総頸動脈の全周を囲み浸潤した.化学療法終了後,病巣の増大から単発性の肺転移と考え,右肺下葉切除術を行った.術後,経過良好で,厳重な経過観察中である

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記述言語：日本語   出版者・発行元：愛媛医学会  

前立腺癌に対する内分泌療法の治療効果や再発・転移を予測するため,肝細胞増殖因子(HGF)の発現を解析した.生検により前立腺癌と診断した28例を対象とし,去勢術もしくは黄体形成ホルモン放出ホルモン製剤を含む内分泌療法を行った.内分泌療法開始後3ヵ月において血清HGF中央値の下降(0.40→0.36ng/ml)を認めたが,血清HGF値が上昇した症例が35.7%(10例)あった.HGF蛋白は間質細胞,癌細胞細胞質,および核に発現し,c-met蛋白は癌細胞細胞質に発現した.内分泌療法に伴う血清HGF値の推移に一定の傾向はみられなかった.しかし,局所におけるHGF/c-met系は前立腺癌の進展の多くの段階で関与していることが示唆された

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：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

CiNii Books

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その他リンク： https://jlc.jst.go.jp/DN/JALC/00250292989?from=CiNii

記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

64歳男.原発不明頸部リンパ節・肺転移巣に対してUFT内服治療を開始後,約3週で両側足・手背部に圧痕浮腫が出現した.圧痕浮腫はUFT内服を中止しても変化なく,UFT治療を再開すると増悪した.免疫学的検査でリウマチ因子が陰性を示したこと,足関節のMRI検査で滑膜の肥厚や滑膜炎の所見を認めたことなどからRS3PEと診断した.ステロイド療法を行い,浮腫は消失した

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本頭頸部癌学会  

口腔癌20例に対し,RI法と色素法によるセンチネルリンパ節(SN)同定と,準連続切片および定量化PCR法による術中診断を応用したSN生検を試みた.癌発生部位は舌10例,下顎歯肉5例,上顎歯肉2例,口底2例,頬粘膜1例であった.全例SNを同定でき,検出個数は1例当たり平均2.1個であった.リンパ節転移を同定できたのは7例で,陰性と判定し術後後発転移を来たしたのは1例であった.すなわちSN生検の感度は87.5%,特異度100%,精度95.0%,陽性的中率100%,陰性的中率92.3%であった.舌癌例ではSNはオトガイ,顎下部リンパ節,内深頸リンパ節などで検出され,症例により様々であった.リンパ節転移を同定できた4例中3例では,転移陽性リンパ節はすべてSN生検で同定されたリンパ節であった.他の1例は転移陽性リンパ節がSNで検出された部位以外に認めた.口腔癌においてSN生検は有用であり,頸部郭清術の指標として臨床応用可能と考えられた

DOI： 10.5981/jjhnc.31.79

Scopus

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE  

Malignant mesothelioma is a rare tumor arising from the pleura or peritoneum. Distant hematogenous metastasis is seen in more than half of cases, preferentially to the brain, lung, bone and soft tissues [Br. J. Dis. Chest 70 (1976) 246]. There has been only one previous report of this tumor metastasizing to the jaw bone [Pathologica 92 (2000) 273].

DOI： 10.1016/j.ijom.2003.10.017

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記述言語：日本語   出版者・発行元：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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記述言語：日本語   出版者・発行元：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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記述言語：日本語   出版者・発行元：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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記述言語：日本語   出版者・発行元：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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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

81歳男.歯科医院で右側下顎切歯抜歯処置が行われたあと同部に無痛性腫脹を生じ,生検で基底細胞癌と診断され紹介受診した.パノラマX線検査および咬合法X線検査で右側下顎小臼歯〜左側下顎切歯の歯槽部に不均一なX線透過像と不透過像の混在を認めた.生検の病理所見は線維形成がほとんどみられず,腫瘍実質が密に増生し,一部では基底細胞と連続性をもって増殖していると思われる部分もみられたことから基底細胞癌が疑われた.しかし,手術標本で腫瘍全体をみると大部分が著明な間質の線維形成を主とする線維形成性エナメル上皮腫の特徴的病理像を呈していた.手術は下顎骨辺縁切除術を行い,術後4ヵ月の現在再発は認めていない

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Vascular endothelial growth factor (VEGF) A is known to play an important role in tumor angiogenesis. The additional members of the VEGF family, VEGF B, C and D have been discovered. VEGF C and D show some selectivity toward lymphatic endothelial cells. However, whether VEGF family members play a role in tumor angiogenesis and lymph node metastasis is largely unknown. The aim of the present study was to explore the role of VEGF family members in oral squamous cell carcinoma (OSCC). We evaluated the expression of VEGF family members by immunohistochemistry, reverse transcription-polymerase chain reaction, and western blotting. All VEGF members were expressed at different levels in OSCC. Immunohistological analysis of VEGF family members expression and microvessel density revealed a correlation between VEGF A and B expression and tumor angiogenesis. Although VEGF A and B expression were detected in both node-positive and node-negative OSCC, VEGF C and D expression was detected frequently in node-positive tumors compared to node-negative tumors. These findings suggest a possible relationship between the expression level of VEGF C and/or D and development of lymphatic tumor spread. (C) 2003 Elsevier Ltd. All rights reserved.

DOI： 10.1016/S1368-8375(03)00127-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

High expression of epidermal growth factor receptor (EGFR) is frequently observed in many solid tumor types including oral squamous cell carcinomas (OSCC). Recently, the results of preclinical studies and early clinical trials targeting the EGFR have shown evidence of the activity. In this study, gefitinib ('Iressa', ZD1839), an EGFR-tyrosine kinase inhibitor, inhibited cell proliferation and upregulated p27(KIP1) in OSCC cells. Growth inhibition was observed in OSCC xenografts when mice were treated with gefitinib in vivo. A flow cytometric analysis demonstrated that treatment with gefitinib induced accumulation in G1 phase, accompanied by a decrease in the percentage of cells in S phase. Apoptosis was not seen in this study. Cell growth was inhibited by an increase of the cell cycle inhibitor p27(KIP1) and a decrease of its ubiquitin ligase subunit Skp2. (C) 2003 Elsevier Ltd. All rights reserved.

DOI： 10.1016/S1368-8375(03)00131-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

Molecular blockade of EGFR with either an EGFR MAb or an EGFR TK1 enhances the radiosensitivity of human SCCs. In the present study, we investigated whether treatment with the EGFR TK1 gefitinib (Iressa, ZDI839) improves the response to radiotherapy in the OSCC cell lines HSC2 and HSC3. We examined potential mechanisms that may contribute to the enhanced radiation response induced by gefitinib. Growth inhibition was observed in vitro with radiation or gefitinib. A cooperative antiproliferative effect was obtained when cancer cells were treated with radiation followed by gefitinib. Cells treated with a combination of radiation and gefitinib arrested in G(1) and G(2)-M phases, with a decrease in the S-phase population. While radiation alone did not significantly affect MEK 1/2 and p38 MAPK autophosphorylation, the combination of gefitinib and radiation completely inhibited the downstream signaling of EGFR. Results from DNA damage repair analysis in cultured OSCC cells demonstrated that gefitinib had a strong inhibitory effect on DNA-PKc pathways after radiation. Tumor xenograft studies demonstrated that the combination of gefitinib and radiation caused growth inhibition and tumor regression of well-established OSCC tumors in athymic mice; tumor volume was reduced from 1,008.2 to 231.4 mm(3) in HSC2 cells (p < 0.01) and from 284.2 to 12.4 mm(3) in HSC3 cells (p < 0.01). Immunohistochemical analysis of OSCC xenografts revealed that gefitinib caused a striking decrease in tumor cell proliferation when combined with radiotherapy. Overall, we conclude that gefitinib enhances tumor radioresponse by multiple mechanisms that may involve antiproliferative growth inhibition and effects on DNA repair after exposure to radiation. (C) 2003 Wiley-Liss, Inc.

DOI： 10.1002/ijc.11437

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記述言語：日本語   出版者・発行元：(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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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. Recently, we have demonstrated that PPARgamma is expressed in human salivary gland tumors and its ligands inhibit the growth of cultured salivary gland cancer cells. However, expression and function of PPARgamma in normal and neoplastic human oral squamous epithelium remains unclear. in the present study, we examined PPARgamma expression in human oral squamous cell carcinoma (OSCC) and tested its ligands for any antitumor effect. PPARgamma mRNA was detected by RT-PCR in some OSCC tissues and cultured cells, but the PPARgamma protein showed neither expression nor ligand-induced transcriptional activity. Despite loss of PPARgamma function, synthetic PPARgamma ligands caused significant dose-dependent inhibition of cancer cell growth. These results suggest that PPARgamma function is inactivated in OSCC cells and the anti-proliferative effect of its synthetic ligands is independent of PPARgamma. (C) 2003 Elsevier Ltd. All rights reserved.

DOI： 10.1016/S1368-8375(03)00108-8

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

73歳男.右側上顎歯肉部の接触痛を主訴とした.右側上顎歯肉臼歯相当部に22×23mm大の一部潰瘍を伴う腫瘍を認めた.生検により扁平上皮癌と診断し,手術前日に99mTcスズコロイドを用いたRI法で,センチネルリンパ節の同定を行った結果,顎下,上内深頸部に各1個のセンチネルリンパ節が検出された.色素法を併用したセンチネルリンパ節生検術と上顎骨部分切除術を施行し,センチネルリンパ節を摘出した.これらのセンチネルリンパ節は通常の最大割面での術中迅速病理組織診断では転移陰性であったが,上内深頸リンパ節において150μm間隔で作成した準連続切片の2枚に腫瘍細胞の存在が確認できた.腫瘍細胞はサイトケラチン抗体による迅速免疫染色でも確認された.以上により,上内深頸リンパ節に転移陽性と診断し,右側全頸部郭清術変法を施行した.しかし,検索結果が診断されるまでに2時間10分を要し,リアルタイム定量化RT-PCRの結果を得るまでには2時間50分を要しており,時間短縮,効率化が望まれた

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

We examined the role of chemokine signaling on the lymph node metastasis of oral squamous cell carcinoma (SCC) using lymph node metastatic (HNt and B88) and nonmetastatic oral SCC cells. Of 13 kinds of chemokine receptors examined, only CXCR4 expression was up-regulated in HNt and B88 cells. CXCR4 ligand, stromal-cell-derived factor-1alpha (SDF-1alpha; CXCL12), induced characteristic calcium fluxes and chemotaxis only in CXCR4-expressing cells. CXCR4 expression in metastatic cancer tissue was significantly higher than that in nommetastatic cancer tissue or normal gingiva. Although SDF-1alpha was undetectable in either oral SCC or normal epithelial cells, submandibular lymph nodes expressed the SDF-1alpha protein, mainly in the stromal cells, but occasionally in metastatic cancer cells. The conditioned medium from lymphatic stromal cells promoted the chemotaxis of B88 cells, which was blocked by the CXCR4 neutralization. SDF-1alpha rapidly activated extracellular signal-regulated kinase (ERK)1/2 and Akt/protein kinase B (PKB), and their synthetic inhibitors attenuated the chemotaxis by SDF-1alpha. SDF-1alpha also activated Src family kinases (SFKs), and its inhibitor PP1 diminished the SDF-1alpha-induced chemotaxis and activation of both ERK1/2 and Akt/PKB. These results indicate that SDF-1/CXCR4 signaling may be involved in the establishment of lymph node metastasis in oral SCC via activation of both ERK1/2 and Akt/PKB induced by SFKs. (C) 2003 Elsevier Inc. All rights reserved.

DOI： 10.1016/S0014-4827(03)00344-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

High expression of epidermal growth factor receptor (EGFR) is frequently observed in many solid tumor types including oral squamous cell carcinomas (OSCC). This study investigated whether treatment with gefitinib ('Iressa'), an EGFR-tyrosine kinase inhibitor, would inhibit the metastatic spread in OSCC cells. This was evaluated using orthotopic xenografts of highly metastatic OSCC. Metastasis was observed in six of 13 gefitinib treated animals (46.2%), compared with all of 12 control animals (100%). After exposure to gefitinib, OSCC cells showed a marked reduction in cell adhesion ability to fibronectin and in the expression of integrin alpha3, alphav, beta1, beta4, beta5 and beta6. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/S0304(03)00464-6

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DOI： 10.1097/01.coc.0000091356.25759.69

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

精神障害或いは脳循環障害を有し,著しく意思疎通の困難な習慣性顎関節脱臼患者に対し,T字型チタンミニプレートを用いたBuckley-Terry法よる手術療法を施行した.症例1は47歳男.うつ病で入院加療中である.ほぼ毎日頻回に左側顎関節脱臼を認めるようになり,自己整復も不可能となった.左側習慣性顎関節前方脱臼と診断し,全身麻酔下にT字型チタンミニプレートを用いた下顎頭の前方運動抑制術を左側に施行した.術後2週間,弾性包帯による開口制限を行った.以後,脱臼は認められず経過良好である.症例2は50歳男.水頭症,脳梗塞による右側片麻痺,聾唖が認められた.脱臼を頻回に繰り返した.両側習慣性顎関節前方脱臼と診断し,全身麻酔下にT字型チタンミニプレートを用いた下顎頭の前方運動抑制術を両側に施行した.術後10日間,顎間固定を行った後,経過良好にて退院した.以後,脱臼認められず経過良好である

DOI： 10.5794/jjoms.49.544

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その他リンク： http://search.jamas.or.jp/link/ui/2004048991

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

Oral squamous cell carcinoma (OSCC) cells can invade adjacent tissues and the vascular system at an early stage of tumor progression. In the present study, we have attempted to detect circulating cancer cells. We used human OSCC cells expressing green fluorescent protein (GFP) in an orthotopic nude mouse model and were able to detect GFP-expressing cells using a fluorescence activated cell sorter and fluorescence microscopy. We also detected the expression of GFP, squamous cell carcinoma antigen (SCCA), or epidermal growth factor receptor (EGFR) mRNA in the blood of tumor-bearing mice by conventional reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR (TaqMan RT-PCR). TaqMan RT-PCR was the more sensitive method to detect the circulating cancer cells. Furthermore, we examined the expression of SCCA and EGFR mRNA in the peripheral blood of patients with OSCC by conventional RT-PCR and TaqMan RT-PCR. We detected SCCA and EGFR mRNA in few cases by conventional RT-PCR, whereas TaqMan RT-PCR showed their expression in about 50% of cases. However, there was no correlation between detection of circulating viable cancer cells and metastasis to lymph nodes and distant organs. These results suggest that TaqMan RT-PCR is a very useful method and both SCCA and EGFR mRNA may be available as a marker for detection of circulating cancer cells.

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

82歳男.左側下顎歯肉の疼痛を主訴に他院歯科を受診,単純X線・CT所見から悪性病変を疑われ加療目的で来院した.初診時口腔内所見では左側下顎臼歯相当部歯肉に潰瘍形成を伴う表面カリフラワー様の41×22mm大の腫瘍を認め,パノラマX線写真では左側下顎前歯から臼歯部にかけて下顎管におよぶ辺縁不整の骨吸収像を認めた.入院後の生検にて高分化型扁平上皮癌と診断され,術前治療としてX線外照射1日1回2Gy・週5日とTS-1(120mg/日)の連日内服投与を開始した.投与3週目より副作用としてgrade 3の口内炎と下痢を認めたため,放射線治療(総線量36Gy)とTS-1の投与(総投与量1800mg)を中止した.治療中止後4週目には口内炎は消失,肉眼的に腫瘍は完全に消失し,病理組織学的所見にも生存腫瘍細胞は認められなかった.治療終了後6ヵ月の現在,再発・転移は認めていない.以上よりTS-1併用放射線療法は口腔癌に対する有用な治療法の1つであると考えられた

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

Hepatocyte growth factor (HGF) has been proposed to be an autocrine/paracrine growth factor for carcinomas of various organs. We recently demonstrated that HGF produced by prostate-derived stromal cells was a paracrine growth factor that stimulated the growth of androgen-independent prostate cancer cells in vitro and in vivo. To assess possible involvement of HGF in prostate cancer, we examined the immunohistochemical expression and localization of HGF and c-Met/HGF receptor in benign and malignant human prostate tissues. In benign glands, columnar cells generally were negative for c-Met, but basal cells were stained uniformly at a high level. In high-grade prostatic intraepithelial neoplasia (PIN) and carcinoma, more than 50% of these foci were stained uniformly. There was no difference in the frequency of positively stained cells by Gleason score. The prostate stroma stained diffusely for HGF, and the staining intensity varied depending upon the amounts of smooth-muscle cells that were stained more intensely than the connective-tissue matrix. A great majority of benign columnar cells were negative for HGF whereas high-grade PIN and carcinoma foci stained focally for HGF. Hormonal ablation therapy prior to prostatectomy did not seem to alter the expression of HGF/c-Met in carcinoma cells. These results indicate that, as the degree of neoplasia progresses, epithelial cells begin to express c-Met protein, that PIN and carcinoma may have developed a c-Met-HGF paracrine loop with the stroma, and that in some carcinoma foci an autocrine loop may operate with HGF expressed by carcinoma cells themselves.

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記述言語：日本語   出版者・発行元：(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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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

54歳男.開口障害を契機に筋電図検査を施行したが神経原性の筋障害は認められなかった.パノラマX線写真及びCTでは異常所見はなく,MRIではT2強調画像にて両側咬筋内に低信号領域を認め,同部にエコー検査で信号強度の亢進が認められた.約2ヵ月前に顔面を殴打される等の暴行を受けていたことから,咬筋瘢痕性開口障害との臨床診断を行い,開口器による開口訓練,筋弛緩剤と消炎鎮痛剤による保存的治療を行ったが奏効せず,咬筋筋膜剥離,咬筋筋膜減張切開を目的とした手術を行った.術後の自力開口訓練を行い,赤外線温熱療法と筋弛緩剤,瘢痕抑制剤を併用したところ,術後3ヵ月目には開口障害は著明に改善した

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記述言語：英語   出版者・発行元：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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記述言語：日本語   出版者・発行元：愛媛医学会  

18歳男.出生時に左側唇顎口蓋裂を認め,生後3ヵ月に口唇形成術,1歳時に口蓋形成術,5歳時に口唇・口蓋垂修正術を施行していた.しかし,その後も中顔面の陥凹感が持続し,上顎骨発育不全による上顎後退症と診断し,二期的上下顎骨骨切り術にRED systemによる仮骨延長法を併用し,良好な治療結果が得られた

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記述言語：日本語   出版者・発行元：(株)先端医学社  

放射線同位元素によるセンチネルリンパ節検出は概ね安定してきたが,問題はその微小転移の診断方法である.微小転移の確実な診断方法を開発することがsentinel node navigation surgery(SNNS)を普及させる上で大変重要と考えられる.著者等は扁平上皮癌である日腔癌微小転移の形態学的診断及び遺伝子診断法について研究を続けてきた.遺伝子診断法の口腔癌特異的マーカーは見い出されていないが,SCC抗原mRNAを利用している.その結果,術中遺伝子診断法開発のため,ミニカラムやLightCyclerを使用することで検査時間が2時間以内に短縮でき,臨床応用の道が開けてきた

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

標題の4例を報告した.顎骨骨髄炎発症の契機は全例が抜歯後感染であった.3例は下顎だけでなく,骨髄炎に罹患しにくいとされている上顎にも発症しており,大理石骨病の易感染性が示された.治療は,掻爬や腐骨除去のみの処置では再発を繰り返し,顎骨の区域切除,部分切除によって良好な経過が得られた

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

2002年3月〜9月に初回治療を行った口腔悪性腫瘍10症例を対象に,核医学的検出(RI)によるセンチネルリンパ節生検を行い,微小転移診断を術中迅速診断として応用することを試みた.センチネルリンパ節の同定はRI法と色素法の併用で行ったが,その一致率は80%で,各症例1個或いは2個のセンチネルリンパ節を同定し得た.10症例のうち3症例5個のセンチネルリンパ節において転移巣が検出された.転移陽性センチネルリンパ節5個のうち,4個は病理部による術中迅速病理組織検査にて診断し得た.遺伝子診断では,いずれの症例においても29から31サイクルでPBGD遺伝子の増幅が認められ,RNAの抽出及びRNAを鋳型として直接用いるワンステップRT-PCR法に問題は認められなかった

DOI： 10.5981/jjhnc1974.29.64

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：APSIT ASSOC PROM STUD IMMUNOL TUMOR  

Recently, a new concept for cancer therapy termed "tumor dormancy therapy" has been proposed. The concept of this therapy is to prolong the survival time of cancer patients while maintaining their quality of life. We have been developing a differentiation-inducing therapy, which is included in the tumor dormancy therapy, for salivary gland cancer. In this study, we examined the effect of a differentiation-inducing drug, Vesnarinone on the growth of several cancer cells, and examined the molecular mechanism by which Vesnarinone induces the cyclin dependent kinase inhibitor, p21(waf1) in the cancer cells. Vesnarinone significantly suppressed the growth of TYS (salivary gland cancer cells), PC3 (prostate cancer cells), and A431 (squamous cell cancer cells). Furthermore, Vesnarinone dose-dependently enhanced the expression of p21(waf1) mRNA in TYS cells. Using the luciferase reporter assay it was found that the enhancement of p21(waf1) mRNA expression by Vesnarinone was through direct transcriptional activation of the p21(waf1) promoter. Thus, analyzing the molecular mechanisms of differentiation inducing drugs may lead to the development of a new therapeutic strategy for several human malignancies, including salivary gland cancer.

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記述言語：日本語   出版者・発行元：(一社)日本口腔診断学会  

79歳男で,口腔内の白斑・潰瘍形成を主訴とした.自己抗体の推移と臨床症状との関連が認められ,ステロイドの全身投与により症状の軽減をみたことから,原因疾患として自己免疫疾患(ベーチェット病,全身性エリテマトーデス,進行性全身性硬化症など)を疑った.しかし,高齢者のため発熱や関節痛等の症状がなく,いずれの疾患も診断基準を満たさなかった.そのため確定診断には至らなかったものの,これら疾患の不全型と考えステロイド剤の全身投与を行ったところ口内炎はほぼ消退した

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

1991〜2000年に加療した口腔扁平上皮癌患者の内,十分な臨床病理組織学的検討が行えた75例を対象に,Skp2,Jab1とp27KIP1の発現ならびに臨床病理学的因子との関連を検討した.口腔癌におけるp27KIP1の発現はSkp2及びJab1の発現と逆相関を示し,p27KIP1の発現がこれらの蛋白分解機構によって制御されていることが示唆された.また,これらの蛋白の発現が,頸部リンパ節転移ならびに予後と関連したことから,p27KIP1とその制御因子であるSkp2及びJab1が,口腔癌の細胞周期の制御のみならず癌の進展にも関与していることが示唆された

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

Pre-therapeutic evaluation of p53 gene is very important for treating patients with head and neck cancer. However, the analysis for p53 gene has generally been done by immunohistochemistry, polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) and direct sequencing. Functional analysis system for p53 transcriptional activity in mammalian cells is now required. We developed a functional analysis system for p53 transcriptional activity in cancer cells. We used two human head and neck cancer cell lines harboring mutated p53 gene, HSG (Asn30Ser) and TYS (Asp281His), and a human osteosarcoma cell line, Saos-2 as a control. We transfected these cells with luciferase reporter plasmids containing promoter sequence of p53 target genes (p21(waf1), BAX, MDM2, p53AlP1 or PUMA). After treating the cells with chemotherapeutic drugs, alteration of the luciferase activity was measured. In HSG cells, none of the target gene promoters was activated by treatment with chemotherapeutic drugs. In TYS cells, p21(waf1) promoter was markedly activated by treatment with chemotherapeutic drugs, but Bax and p53AlP1 promoter was not activated. This type of mutated-p53 in TYS cells prevents cell death from DNA damage, and probably accumulates genetic alterations and accelerates the malignant progression of the cells by DNA damaging therapy. Thus, analysis for the diverse function of mutated-p53 may help to determine the therapeutic strategy, especially for chemotherapy and radiation in the individual patients with head and neck cancer.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Flavopiridol is a synthetic flavone that inhibits tumor growth by suppressing cyclin-dependent kinases (CDKs). We have investigated effects of flavopiridol in oral squamous cell carcinoma (OSCC). Flavopiridol was found to inhibit the growth of OSCC cells in a time- and dose-dependent manner. Induction of apoptosis was observed in all cells showing accumulated cells with sub-G1 DNA contents, DNA fragmentations, and PARP cleavages. While Bcl-2 and Bax expression did not change, Bcl-xL was down regulated and Bcl-xs was up-regulated after being exposed to flavopiridol. Flavopiridol treatments also resulted in remarkable reductions of cyclin A, cyclin B, and cyclin D1 expressions. We also found that expression levels of CDK activation kinase and CDC25C were reduced, and p34 inactive form CDK2 were up-regulated. Our data indicate that flavopiridol has growth inhibition activities against OSCC. Flavopiridol not only inhibits CDKs directly, but it also inhibits the CDKs activation pathway and activates the Bcl-x apoptotic pathway. © 2002 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S1368-8375(02)00019-2

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記述言語：日本語   出版者・発行元：(株)篠原出版新社  

正中部に発生した口腔扁平上皮癌20例(男16,女4,平均61.1歳)について,リンパ節転移様式,原発巣の進展範囲とリンパ節転移部位との関係について検討を行った.リンパ節転移は6例(口底3例,上顎歯肉2例,下顎歯肉1例)にみられた.この6例の転移部位は片側が4例で両側が2例であった.又,1例は上内深頸領域のリンパ節に直接転移していた.正中線から左右への腫瘍進展範囲とリンパ節転移部位との間に明らかな相関はみられなかった.以上より正中部口腔扁平上皮癌では大きさ,進展形態に拘わらず両側かつ上内深頸領域のリンパ節へ転移する可能性があることが示唆された

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その他リンク： http://search.jamas.or.jp/link/ui/2003148743

記述言語：日本語   出版者・発行元：愛媛医学会  

1977年〜2001年までに骨格性顎変形症の診断で顎矯正手術を施行した212症例に臨床統計的検討を行った.男性62例,女性150例であり,男女比は1:2.4であった.年齢は15歳以上20歳未満が半数以上を占めていた.主訴は機能性要因の咬合不全(127例),口唇閉鎖不全(4例),発音障害(3例)が多く,審美性要因ではオトガイ突出(63例),下顎非対称(8例),上顎突出(2例)であった.診断は下顎前突出の161例が最大であり,全体の76%を占めていた.術式は下顎後退術(SSRO)が169例と最多で,臨床診断の下顎前突症の症例数にほぼ一致していた.高度の変形を持つ患者に対しても,上下顎同時移動術,SSROと下顎枝垂直骨切り術の組み合わせ手術,仮骨延長法などの応用で良好な結果を得ていた.固定材料は1992年以降チタンプレートが主であり,症例により生体内吸収性のポリ-L乳酸スクリュー,およびプレートが使われていた.SSROの手術時間,出血量は,それぞれ平均218分,平均314mlであった

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

Tumor-associated macrophages (TAMs) have been shown to display both positive and negative effects on tumor growth of various cancer. In this study, TAMs were immunohistochemically labeled using CD68 antibody in 82 oral cancer. Macrophage index (MI) were analyzed in association with clinical and pathological factors, intratumoral microvessel density (IMVD) and angiogenic factors including VEGF and TP. Significantly higher number of CD68-positive cells was noted in oral cancer. TAM expressions were significantly associated with stages of invasion, IMVD, and angiogenic factors. These findings suggest that TAMs possibly play a role in angiogenesis during oral cancer progression.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

We previously demonstrated that a differentiation inducing drug, vesnarinone induced the growth arrest and p21(waf1) gene expression in a human salivary gland cancer cell line, TYS. In the present study, we investigated the mechanism of the induction of P21(waf1) gene by vesnarinone in TYS cells. We constructed several reporter plasmids containing the p21(waf1) promoter, and attempted to identify vesnarinone-responsive elements in the p21(waf1) promoter. By the luciferase reporter assay, we identified the minimal vesnarinone-responsive element in the p21(waf1) promoter at -124 to -61 relative to the transcription start site. Moreover, we demonstrated by electrophoretic mobility shift assay that Sp1 and Sp3 transcription factors bound to the vesnarinone-responsive element. Furthermore, we found that vesnarinone induced the histone hyperacetylation in TYS cells. These results suggest that vesnarinone directly activates p21(waf1) promoter via the activation of Sp1 and Sp3 transcription factors and the histone hyperacetylation in TYS cells. (C) 2002 Cancer Research UK.

DOI： 10.1038/sj.bjc.6600592

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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<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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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. It is expressed in several tissue types, including adipose tissue in which it stimulates adipogenesis. Recent studies have demonstrated that PPARgamma ligands induce cellular differentiation and inhibit cell growth in carcinomas of various organs including the breast, prostate, lung, colon, stomach, bladder, and pancreas. However, whether PPARgamma is expressed in human salivary gland tumors and its function in this tissue is unknown. In the present study, we examined PPARgamma gene expression in human salivary gland cancer cells and tested its ligands for any antitumor effect. PPARgamma mRNA was detected by RT-PCR in both benign and malignant salivary gland tumor tissues. The effect of PPARgamma on cell growth was investigated using four human salivary gland cancer cell lines; HSG, AZA3, HSY and TYS, which were confirmed to express PPARgamma1 mRNA and protein. Retinoid X receptor a protein, which forms heterodimers with PPARgamma, was also detected in all the cells tested. Data obtained by luciferase assay indicated that the intrinsic PPARgamma protein was activated by the synthetic ligands, troglitazone and pioglitazone, but not by the natural ligand, 15-deoxy-Delta(12), (14)-prostaglandin J(2). The synthetic PPARgamma ligands, particularly troglitazone, caused significant dose-dependent inhibition of cancer cell growth. Furthermore, the overexpression of PPARgamma1 or PPARgamma2 in cancer cells also reduced significantly their growth rate. These results suggest that PPARgamma and its synthetic ligands suppress the growth of human salivary gland cancer cells and it may be a useful molecular target for cancer treatment.

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記述言語：日本語   出版者・発行元：(一社)日本頭頸部癌学会  

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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会  

35歳女(症例1).右側上顎臼歯部の疼痛を訴え受診し,右側上顎第一大臼歯の抜髄処置を受け疼痛は軽減したが右側顔面に違和感が出現した.顔面麻痺を評価する40点法の表情筋スコアは16点であった.ウイルス学的検査ではHSV,VZVともに有意な上昇を認めずBell麻痺と診断した.抗ウイルス剤とステロイド併用療法を行い.3週後に神経麻痺症状は消失した.58歳女(症例2).右側耳介部から顎下部にかけ違和感を覚え,範囲が後頭部まで拡大し自発痛も出現した.顔面麻痺の表情筋スコアは18点で,ウイルス検査でHSV,VZVともに陰性であった.Bell麻痺と診断し抗ウイルス剤とステロイド併用療法で3週後に神経麻痺症状は消失した

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

The measurement of the intra-tumoral level of thymidylate synthetase (TS), and dihydropyrimidine dehydro-genase (DPD), may be useful in predicting tumor sensitivity to 5-fluorouracil (5-FU). In this study, we examined the mRNA levels of DPD and TS in 28 oral squamous cell carcinomas (SCC), and 22 salivary gland tumors by semiquantitative reverse transcription polymerase chain reaction. Then we examined the correlation of the responsiveness of the patients with oral SCC to 5-FU with the intra-tumoral levels of DPD and TS mRNA. All specimens were obtained at the biopsy before treatment, and then the patients were treated by oral administration of a 5-FU compound (UFT), the irradiation of cobatt-60 (upto 60 Gy) and injection of an immuno-potentiator (OK-432). Intra-tumoral levels of DPD mRNA in the patients who showed CR (complete response) and PR (partial response) were significantly lower than those in the patients who showed NC (no change). However, intratumoral levels of DPD mRNA did not correlate with the local recurrence of the tumor during the observation period after initial treatment with or without surgical resection of the residual tumors. On the other hand, TS mRNA levels in the tumors did not correlate with any clinico-pathological parameters. These observations suggest that intra-tumoral levels of DPD mRNA may predict the tumor response to 5-FU-based chemo-immuno-radiation therapy in the patients with oral SCC.

DOI： 10.3892/ijo.19.5.953

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC INVESTIGATIVE PATHOLOGY, INC  

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors and is expressed in several types of tissue. Although PPAR gamma reportedly is expressed in normal urothelium, its function is unknown. We examined the expression of PPAR gamma in. normal urothelium and bladder cancer in an attempt to assess its functional role. Immunohistochemical staining revealed normal urothelium to express PPAR gamma uniformly. All low-grade carcinomas were positive either diffusely or focally, whereas staining was primarily focal or absent in high-grade carcinomas. A nonneoplastic urothelial cell line (1T-1), a low-grade (RT4) carcinoma cell fine, and two high-grade (T24 and 253J) carcinoma cell lines in culture expressed PPAR gamma mRNA and protein. Luciferase assay indicated that PPAR gamma was functional. PPAR gamma ligands (15-deoxy-Delta (12,14)-prostaglandin J(2), troglitazone and pioglitazone) suppressed the growth of nonneoplastic and neoplastic urothelial cells in a dose-dependent manner. However, neoplastic cells were more resistant than were nonneoplastic cells. Failure to express PPAR gamma or ineffective transcriptional activity may be some of the mechanisms responsible for resistance to the inhibitory action of PPAR gamma ligands.

DOI： 10.1016/s0002-9440(10)61730-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC INVESTIGATIVE PATHOLOGY, INC  

The objective of the present study is to examine the role of prostate stromal cells on growth and progression of prostate cancer. Go-inoculation of androgen-independent carcinoma cells (PC-3 and GA-7T2) with prostate-derived stromal (P-ST) cells significantly enhanced the growth of carcinoma cells in athymic nude mice. For the in vitro study, a three-dimensional co-culture system was used. It consisted of two layers of collagen gel. Stromal cells were suspended in the lower layer, whereas cancer cells were suspended in the upper layer. Compared to the control culture, the presence of P-ST cells in the lower collagen layer significantly stimulated the growth of carcinoma cells. Such an effect was not demonstrated when carcinoma cells were co-cultured with either bone marrow-derived or skin-derived stromal cells. We identified hepatocyte growth factor (HGF) as the principal growth factor released by P-ST cells but not by bone marrow-derived or skin-derived stromal cells. Neutralizing antibodies against HGF completely abrogated the stimulatory effect of P-ST cells. Exogenous HGF likewise stimulated the growth of carcinoma cells in vitro and in vivo. These results suggest that HGF produced by P-ST cells is a paracrine growth factor that stimulates the growth of androgen-independent prostate cancer cell lines.

DOI： 10.1016/s0002-9440(10)64593-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

An in vitro study was conducted to determine if malignant transformation can be induced in human urothelial cells immortalized with human papillomavirus E6/E7 genes. A clone designated 1T1 was isolated and then stably transfected with an acyl CoA oxidase (ACOX)-expression construct. The cells generated H2O2 in a large quantity from the substrate linoleic acid (LA). After 56 days of LA treatment, cells persistently formed an epithelial cyst in athymic nude mice with an occasional intracystic epithelial nodule. Our results indicate that human urothelial cells can be transformed to low grade neoplastic cells by H2O2 and suggest that H2O2 may be involved in the development of bladder cancer.

DOI： 10.3892/ijo.15.4.743

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PROFESSOR D A SPANDIDOS  

We examined the gelatinolytic activity in human oral squamous-cell carcinoma tissues in order to evaluate the capability of intravasation and extravasation of cancer cells. By a microdissection-zymography, we demonstrated separately the gelatinolytic activities in cancer cell nests and stroma adjacent to the cancer cells. The gelatinolytic activities, such as pro-matrix metalloproteinase (MMP)9 and active-MMP2 in most of cancer cell nests were much higher than those of normal gingival epithelium. Moreover, the activities of active-MMP2 in cancer cell nests tf metastatic cancers were significantly higher than those of non-metastatic cancers (p<0.05). These results suggest that active-MMP2 in cancer cells can be a predictive marker for metastasis formation in oral squamous-cell carcinoma patients.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

We have recently isolated TSC-22 (transforming growth factor beta-stimulated clone 22) cDNA as a new anticancer drug (Vesnarinone)-inducible gene in a human salivary gland cancer cell line, TYS. We conducted the present study to examine whether up-regulation or down-regulation of TSC-22 can affect the growth of TYS cells in vitro and in vivo. We constructed an expression vector containing sense-or antisense-oriented human TSC-22 cDNA under the transcriptional control of the SR alpha promoter. We cotransfected TYS cells with the sense or antisense expression vector and pSV2neo and obtained more than 200 G418-resistant colonies in each sense or antisense transfectant. Approximately 80% of representative G418-resistant clones expressed the transcripts from transfected sense or antisense TSC-22 cDNA. To avoid the clonal heterogeneity of the cells, we mixed all of the G418-resistant colonies together in each sense or antisense transfectant and examined the expression of TSC-22 protein, in vitro growth, and the tumorigenicity in nude mice. The expression of TSC-22 protein was examined by solid-phase ELISA using a specific antibody against recombinant TSC-22 protein. The expression of TSC-22 protein was up-regulated in the sense transfectants and down-regulated in the antisense transfectants. Contrary to our expectation, up-regulation of TSC-22 protein did not affect both in vitro and in vivo growth of TYS cells, However, do cvn-regulation of TSC-22 markedly enhanced the growth of TYS cells in vitro and in vivo., Furthermore, we examined the expression of TSC-22 mRNA in several human salivary gland tumors, The mRNA expression of TSC-22 in benign and malignant salivary gland tumors was significantly decreased when compared to that in tumor-free salivary glands (P < 0.05; one-way ANOVA), and in some salivary gland tumors, the expression of TSC-22 mRNA was not detectable by reverse transcription-PCR, These results suggest that down-regulation of TSC-22 may play a major role on salivary gland tumorigenesis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE  

We undertook the present study to clarify the molecular mechanism of the effect of a new anti-cancer drug, vesnarinone, on a human salivary gland cancer cell line, TYS. We isolated TSC-22 cDNA as a vesnarinone-inducible gene from a cDNA library constructed from vesnarinone-treated TYS cells. TSC-22 was originally reported as a transforming growth factor (TGF)-beta-inducible gene. The expression of TSC-22 was up-regulated within a few hours after treatment with vesnarinone and was continued for 3 days. The level of TSC-22 mRNA in PIS cells was continuously increased until the cells reached confluency. Furthermore, the induction of TSC-22 by vesnarinone was inhibited by treatment with cycloheximide. When we treated the cells with an antisense oligonucleotide against TSC-22 mRNA under quiescent conditions, the antisense oligonucleotide stimulated the growth of TYS cells; however, under growing conditions the antisense oligonucleotide did not affect cell growth. Furthermore, the antisense oligonucleotide suppressed the antiproliferative effect of vesnarinone. These results suggest that TSC-22 may be a negative growth regulator and may play an important role in the antiproliferative effect of vesnarinone.

DOI： 10.1038/bjc.1998.11

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記述言語：日本語   出版者・発行元：四国歯学会  

ベスナリノンはヒト唾液腺癌細胞(TYS)でTGF-β1或いは他の蛋白質を介したTSC-22遺伝子の誘導,更に直接作用或いはTGF-β1を介したp21WAF1遺伝子の誘導により細胞周期をG1期に止め細胞増殖抑制作用を示すことが示唆された

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

We have established human oral-squamous-cancer cell lines, BHY and HN, derived from non-metastatic cancer and metastatic cancer respectively. We examined the expression of matrix-degrading enzymes and their inhibitors in these cell lines. Both cell lines expressed pro-matrix metalloproteinase (MMP)1, proMMP2, proMMP9, membrane-type MMP and urokinase-type plasminogen activator. In addition to these enzymes, BHY cells secreted proMMP7 and procathepsin L, while HN cells secreted a large amount of active MMP2. BHY cells secreted a tissue inhibitor of matrix metalloproteinase, TIMP2, but only a trace level of TIMP1. Contrary to BHY cells, HN cells secreted TIMP1, but only a trace level of TIMP2. When we inoculated these cells into the masseter muscle of nude mice, both types of cell formed solid tumors, whose microscopic appearance was identical to that of the original tumors. BHY tumors were highly differentiated squamous-cell carcinomas, and invasive to the masseter muscle and the mandibular bone. Despite their local aggressiveness, BHY tumors did not metastasize to any distant organs. HN tumors were poorly differentiated squamous-cell carcinomas, weakly invasive to the muscle, but not to the mandibular bone. However, HN tumors frequently metastasized to cervical lymph nodes, These results suggest that the net activity of MMP2. (active MMP2/TIMP2) and cathepsin L secreted from cancer cells may contribute respectively to lymph-node metastasis and to bone invasion by oral cancer cells. (C) 1997 Wiley-Liss, Inc.

DOI： 10.1002/(sici)1097-0215(19970106)70:1<120::aid-ijc18>3.0.co;2-p

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

It has been found by PCR-SSCP analysis and direct DNA sequencing that a human salivary adenosquamous carcinoma-forming cell line, TYS, has a mutant p53 gene at codon 281(Asp--&gt;His). When TYS cells were treated with a differentiation-inducing agent, vesnarinone, cellular proliferation was significantly inhibited on the basis of MTT assay. In addition, it has been found by Northern blotting and/or immunoblotting that expression of p21(WAF1) and transforming growth factor-beta (TGF-beta) is up-regulated by treating TYS cells with vesnarinone. TGF-beta 1 alone also induced p21(WAF1) expression in TYS cells, Moreover, over, it has been shown by ELISA that the treatment of TYS cells with vesnarinone results in the enhanced generation of latent TGF-beta 1. The expression of TGF-beta receptor (TPR), including T beta R-I, T beta R-II and T beta R-III, on TYS cells was detected by affinity cross-linking using I-125-TGF-beta 1 and addition of active TGF-beta 1 into serum-free culture medium inhibited the growth of TYS cells in a concentration-dependent manner. These findings suggest that vesnarinone might directly induce expression of p21(WAF1) gene in TYS cells, the product of which may be associated with the inhibition of cell growth and induce differentiation. (C) 1997 Elsevier Science Ireland Ltd.

DOI： 10.1016/s0304-3835(96)04581-8

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記述言語：日本語   出版者・発行元：中国・四国歯科麻酔研究会  

65歳以上の全身麻酔症例113例について.65歳以上の全身麻酔症例は,対象とした期間の全身麻酔症例総数の約15%を占め,その割合は年々増加傾向を示した.術前合併症は113例中75例に認め,麻酔管理上,問題となるような循環器系,呼吸器系疾患が多かった.術中合併症においても血圧変動を含む循環器系のものが大部分を占めた.これら合併症は積極的にコントロールされ,重篤な合併症は認められなかった

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記述言語：日本語   出版者・発行元：中国・四国歯科麻酔研究会  

燐酸クリンダマイシン誘発アレルギーの病歴を有する42歳の看護婦で,外来歯科治療が予定された.重症な歯科治療恐怖症で,麻酔による問題の既往は否定した.ルーチンの術前身体的検査は正常であった.普通に抜歯を行ったが,直後に呼吸困難を訴え,ヒステリー発作を起こした様に見られ,更に数秒間重症な痙攣が起こった.酸素吸入のみを行った

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI PUBL IRELAND LTD  

The tumors produced by transplantation into nude mice of human adenoid squamous carcinoma-forming cell line TYS, presumably derived from a minor salivary gland, were treated with a differentiation-inducing agent, vesnarinone, which was given per o.s, daily at a dose of 200 mg/kg for 35 days. They were then examined morphologically and immunohistochemically, The vesnarinone treatment resulted in a significant suppression of tumor growth. In addition, tumor nests indicating keratinocyte and acinar cell differentiation were often observed in the treated tumors, but not in untreated controls, Tissue sections from vesnarinone-treated and untreated TYS tumors were stained with monoclonal antibody (NAb) directed to carbohydrate antigen Le(Y) or proliferating cell nuclear antigen (PCNA) and with rabbit polyclonal antibody to p53, Antibody staining patterns were compared with morphological characteristics of cells as revealed by hematoxylin and eosin staining, and DNA fragmentation patterns as revealed by 3'-OH nick-end labelling techniques, Tissue sections from vesnarinone-treated TYS tumors showed positive reaction with nick-end labelling and were extensively stained strongly by anti-Le(Y) MAb, whereas the untreated tumors showed negative reaction with nick-end labelling and were infrequently stained by anti-Le(Y) MAb. Within Le(Y)-positive areas of tissue sections from the vesnarinone-treated tumors, keratinocyte and acinar cell differentiation as well as DNA fragmentation were frequently observed, although not all Le(Y)-positive cells showed such signs of apoptosis. Le(Y)-positive cells showed consistent negative staining by anti-PCNA MAb and anti-p53 rabbit serum. From these findings, it can be considered that vesnarinone has differentiation and apoptosis-inducing activity against TYS cells grown in athymic nude mouse.

DOI： 10.1016/0304-3835(95)03713-7

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：日本心脈管作動物質学会  

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2016-1137

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2016-1147

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記述言語：日本語   出版者・発行元：愛媛医学会  

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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J-GLOBAL

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記述言語：英語   出版者・発行元：日本癌学会  

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記述言語：日本語   出版者・発行元：愛媛医学会  

MicroRNA(miRNA)は約22塩基からなる小分子RNAで、標的mRNAに結合することでその蛋白質発現を阻害する。近年、種々の悪性腫瘍において癌遺伝子的な性質を有するoncogenic miRNA(OncomiR)と癌抑制遺伝子様の機能を発揮するtumor suppressive miRNA(TS-miR)の存在が報告されている。さらに、ヒト体液中からmiRNAが検出できることから有用なバイオマーカー候補としても注目されている。そこで、われわれは口腔癌の診断および治療に有用となるmiRNAを探索した。まず、ヒト口腔癌細胞を用いてヒトmiRNAの網羅的機能解析を行った。ヒトmiRNA918種類に対するアンチセンスオリゴヌクレオチドを用いた網羅的機能阻害解析では、口腔癌細胞の増殖を支持するmiRNAを11種類同定し、その中でもmiR-361-3pの機能阻害は著明な細胞増殖抑制効果を示した。一方、ヒトmiRNA988種類の模倣型合成miRNAを用いた網羅的過剰発現解析では、口腔癌細胞の増殖を抑制するmiRNAを16種類同定し、特にmiR-1289の増殖抑制効果は顕著であった。つづいて、口腔癌患者の血清よりmiRNAを抽出し、マイクロアレイとRT-PCRによる網羅的発現解析を行った。健常者と比較して口腔癌患者では10種類のmiRNAの存在量が有意に低下していた。その中のmiR-26aは口腔癌細胞に対して有意な増殖抑制効果を示した。以上の結果は、ヒト口腔癌細胞の増殖を制御するOncomiRやTS-miR、そして口腔癌患者の体液中で特異的に変動するmiRNAが存在することを示唆している。これらmiRNAが新しい口腔癌の診断や治療のツールとなることを期待している。(著者抄録)

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2015-3107

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2015-3793

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2015-LB-219

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2014-1017

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2014-476

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2014-5033

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：日本語   出版者・発行元：日本口腔組織培養学会  

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記述言語：日本語   出版者・発行元：(NPO)日本口腔科学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2012-720

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2012-1355

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2012-113

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記述言語：英語   出版者・発行元：SPANDIDOS PUBL LTD  

FAT1 [Homo sapiens FAT tumor suppressor homolog 1 (Drosophila)] is an intrinsic membrane protein classified as a member of the cadherin superfamily. The FAT1 gene is a tumor suppressor in humans as well as being the pivotal gene for cell morphogenesis and migration. Deletion of this gene could play a role in the characteristics of oral squamous cell carcinomas (OSCCs), involving cell adhesion, migration and/or invasion. This study investigated the mechanisms by which FAT1 is involved in the biological behavior of OSCCs. First, a rat monoclonal antibody was developed against a FAT1 intracellular domain epitope, and used for an immunohistochemical study of FAT1 in clinically obtained OSCC samples. FAT1 was localized at lamellipodial edges or cell-cell boundaries in normal cells and well differentiated OSCCs, but showed a diffuse cytoplasmic and nuclear distribution in moderately-poorly differentiated OSCCs. FAT1-siRNA was transfected into OSCCs resulting in a drastic inhibition of cell migration and invasion based on the suppression of FAT1 expression and disorganized localization of beta-catenin which is associated with cell polarity and migration. These results suggested that FAT1 may be involved in the migration and invasion mechanisms of OSCCs and, therefore, it could be an important target for the development of new therapeutic strategies.

DOI： 10.3892/or.2011.1324

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE BV  

DOI： 10.1016/j.oraloncology.2011.06.133

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2011-145

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記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）  

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記述言語：英語   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

The serine/threonine kinase Akt has three highly homologous isoforms in mammals: Akt1, Akt2, and Akt3. Recent studies indicate that Akt is often constitutively active in many types of human malignancy. Here we investigated the expression and function of Akt isoforms in human prostatic carcinoma cells. Initially, we used Western blotting to examine Akt expression in four human prostate cancer cell lines. Next, small-interfering RNAs (siRNAs) specific for Akt isoforms were used to elucidate their role on the in vitro and in vivo growth of prostate cancer cells. Expression of Akt1 and Akt2 was detected in all cells tested, but Akt3 was expressed only in cancer cells that did not express androgen receptors. All synthetic siRNAs against Akt isoforms suppressed their expression and inhibited the growth of cancer cells in vitro. Furthermore, atelocollagen-mediated systemic administration of siRNAs significantly reduced the growth of tumors that had been subcutaneously xenografted. These results suggest that targeting Akt isoforms could be an effective treatment for prostate cancers. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2010.07.045

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記述言語：英語   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Early phase prostate cancer is usually androgen-dependent, with the androgen/androgen receptor (AR) signaling pathway playing a central role. At this stage, the cancer responds well to androgen ablation therapy, but prostate cancers eventually acquire androgen independence and more aggressive phenotypes. Several studies, however, have shown that the majority of tumors still express functional AR, which is often amplified and mutated. To determine if the AR is a plausible therapeutic target, we investigated the anti-tumor effect of small interfering RNAs targeting the AR (siAR) in the human prostate cancer cells, LNCaP and 22Rv1, which express mutated AR. In both types of cells, transfection of siAR suppressed mutated AR expression and significantly reduced cell growth. Furthermore, atelocollagen-mediated systemic siAR administration markedly inhibited the growth of 22Rv1 cells subcutaneously xenografted in castrated nude mice. These results suggest that the AR is still a key therapeutic target even in androgen-independent prostate cancer (AIPC). Silencing of AR expression in AIPC opens promising therapeutic perspectives. (C) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2009.12.024

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DOI： 10.1016/j.ijom.2010.02.027

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

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記述言語：英語   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

We previously demonstrated that CD151 forms a functional complex with c-Met and integrin alpha 3/alpha 6 in human salivary gland cancer cells. In the current study, we investigated the involvement of CD151, c-Met, and integrin alpha 3/alpha 6 in the cellular morphogenesis of human breast cancer cells, Knockdown of CD151, integrin alpha 3, or integrin alpha 6 expression abolished branching morphogenesis. Decreased c-Met expression in these cells led to the formation of rudimentary networks and prevented their conversion. Furthermore, hepatocyte growth factor (HGF) promoted cellular morphogenesis by accelerating network reorganization. Immunoprecipitation revealed a specific association between CD151 and c-Met, The involvement of CD151 and integrin alpha 3/alpha 6 in HGF-depenclent signaling was confirmed by the decreased Akt phosphorylation in cells lacking CD151, integrin alpha 3, or integrin alpha 6. Hence, the regulation of CD151 expression might contribute to changes in HGF/c-Met signaling and thereby modulate the phenotypic characteristics of cancer cells. (C) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2009.01.023

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE BV  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE BV  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE BV  

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記述言語：英語   出版者・発行元：PROFESSOR D A SPANDIDOS  

The support mechanisms that are involved in lymph-node metastasis of oral squamous cell carcinoma (OSCC) remain largely unknown. Recent studies have demonstrated that tumor cells express chemokine receptors and use chemokines to metastasize to the target organ in many malignancies in humans. In this study, we examined the expression and function of chemokines and their receptors in OSCC. The expression of chemokine receptors was assessed in eight OSCC cell lines. CXCR3 mRNA and protein were expressed in all the OSCC cell lines examined, while CXCR4 mRNA and protein were expressed only in HSC2, HSC3, and Ca9-22 cells. Treatment with the ligand for CXCR4, stromal cell-derived factor-1 (SDF-1), enhanced the motility and invasiveness of OSCC cells expressing CXCR4. However, the CXCR3 ligand, Mig, did not affect the migration or invasiveness of CXCR3-positive cells. We also evaluated the clinical significance of CXCR4 expression immunohistochemically. CXCR4 expression was detected in 27 (30%) of the 90 OSCC tissues tested, and was localized in the membrane and cytoplasm of cancer cells. There was a highly significant correlation between CXCR4 expression and lymph-node metastasis (P=0.0035). Collectively, these findings suggest that CXCR4 might be involved in the lymph-node metastasis of OSCC.

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記述言語：英語   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

In this study, we have attempted to elucidate the expression and function of CD151 in human salivary gland cancer cells. CD151 expression was detected in Acc2 and AccM cells, but not in normal tissues and primary cultured epithelial cells derived from human salivary gland. CD 151 has been found to function as a molecular linker in the formation of complexes between c-Met/hepatocyte growth factor (HGF) receptor and integrin alpha 3/alpha 6. Knockdown of CD151 or integrin alpha 3/alpha 6 expression almost completely abrogated HGF-stimulated cell growth and migration. In contrast, forced expression of CD151 in Acc2 cells resulted in the increase of the HGF-dependent biological effects. These results suggest that CD151 forms a structural and functional complex with c-Met and integrin alpha 3/alpha 6, and exerts its oncogenic functions through excessive activation of the HGF/c-Met signalling pathway. (c) 2005 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2005.08.106

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記述言語：英語   出版者・発行元：CHURCHILL LIVINGSTONE  

Angiogenesis, the growth of capillary vessels, plays an important role in the metabolic functions of malignant tissues. Tumor growth and malignant transformation are considered to be dominated by uncontrolled angiogenesis. To understand the mechanism of increased vascularity associated with malignant tissues, we immunohistochemically evaluated microvessel density (MVD) and the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived endothelial growth factor (PDGF) in oral cancers. Microvessel density did not differ significantly between normal oral mucosa and epithelial dysplasia, but was significantly increased in tumor tissues. Expression of angiogenic factors was not found in normal oral mucosa, but increased in association with increasing vascularity in OSCC tissue. In tumor tissue, angiogenic factor expression correlated with MVD. MVD in OSCC was related to T stage, tumor-differentiation, and stage of invasion. VEGF expression also correlated with tumor differentiation and the stage of invasion. These findings suggest that VEGF might play an important role in tumor angiogenesis of OSCC.

DOI： 10.1016/j.ijom.2004.10.016

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE BV  

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記述言語：英語   出版者・発行元：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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記述言語：英語   出版者・発行元：AMER SOC INVESTIGATIVE PATHOLOGY, INC  

Support mechanisms involved in growth of androgen-independent prostate cancer are primarily unknown. Hepatocyte growth factor (HGF)/Met has been suggested to be one of them based primarily on immunohistochemical studies. We conducted a series of experiments to assess the role of the HGF/Met system in an androgen-dependent human prostate carcinoma, CWR22 and its androgen-independent derivative, CWR22R. We found that action of HGF changed from paracrine to autocrine in progression to androgen-independent state. CWR22 tumors did not express HGF but expressed Met, whereas prostate stromal cells expressed HGF at a high level. Growth of CWR22 was stimulated either by addition of HGF to the culture or by the presence of prostate stromal cells. on the other hand, CWR22R cells expressed both HGF and Met. Knockdown of Met expression by RNA interference method suppressed the growth of CWR22R cells. Our data suggest that HGF is intimately involved in growth of human prostate cancer and that progression from the androgen-dependent to the androgen-independent state is associated with an adaptive switch in support mechanism from paracrine to autocrine. Our data offer one mechanism to account for androgen-independent human cancer growth.

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記述言語：英語   出版者・発行元：PROFESSOR D A SPANDIDOS  

Stat3 belongs to a family of signal transducers and activators of transcription. Constitutive activation of Stat3 has been observed in many human malignancies. In addition, mutated Stat3 has been shown to possess oncogenic potential on its own, and activation of Stat3 signaling is required for HGF/c-Met-mediated tumorigenesis. In this study, we examined the correlation between Stat3 activation and HGF/ c-Met signaling in samples of oral squamous cell carcinoma (OSCC). Immunohistochemical examination revealed the phosphorylated form of Stat3 in the nuclei of 62/84 OSCC tissue samples but not in normal mucosa, while c-Met expression was detected in 48 samples. Approximately half of the c-Met positive samples also contained phospho-Stat3. There were highly significant correlations between activation of Stat3 and c-Met expression (p=0.00097) and tumor stage. These results indicate that activation of Stat3 mediated by c-Met is frequently associated with the progression of OSCC.

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, is overexpressed in many types of malignant tumors, which in turn may stimulate tumor growth and protect against damage by irradiation or cytotoxic agents. The purpose of this study is to investigate the relationship between the radiation sensitivity and elevated level of COX-2. Radiation sensitivity of the eight oral SCC cell lines differed greatly in their response to radiation. Further, the level of the COX-2 expression correlated inversely with increased tumor radiation sensitivity. The similar significant association between the response to preoperative radiation therapy and COX-2 overexpression was observed in the oral SCC patients. In addition, treatment with a COX-2 selective inhibitor enhanced the radioresponse of HSC-2 cell, which constitutively expressed COX-2. These results suggested that COX-2 expression level correlates to radiation tolerance and the COX-2 selective inhibitor may be a potent enhancer for tumor radioresponse in oral SCC. (C) 2003 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.oraloncology.2003.09.005

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

High expression of epidermal growth factor receptor (EGFR) is frequently observed in many solid tumor types including oral squamous cell carcinomas (OSCC). Recently, the results of preclinical studies and early clinical trials targeting the EGFR have shown evidence of the activity. In this study, gefitinib ('Iressa', ZD1839), an EGFR-tyrosine kinase inhibitor, inhibited cell proliferation and upregulated p27(KIP1) in OSCC cells. Growth inhibition was observed in OSCC xenografts when mice were treated with gefitinib in vivo. A flow cytometric analysis demonstrated that treatment with gefitinib induced accumulation in G1 phase, accompanied by a decrease in the percentage of cells in S phase. Apoptosis was not seen in this study. Cell growth was inhibited by an increase of the cell cycle inhibitor p27(KIP1) and a decrease of its ubiquitin ligase subunit Skp2. (C) 2003 Elsevier Ltd. All rights reserved.

DOI： 10.1016/S1368-8375(03)00131-3

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記述言語：英語   出版者・発行元：PROFESSOR D A SPANDIDOS  

Metastasis to cervical lymph nodes (LN) is significantly associated with the outcome of patients with oral cancer. To provide a useful method for the detection of micrometastases, we analyzed 115 LNs from 10 patients with oral cancer using real-time quantitative polymerase chain reaction (PCR) based on the expression of squamous cell carcinoma antigen (SCCA) and cytokeratin 13 (CK13). The sensitivity and quantification of this method were assessed by means of limited dilution of cultured oral cancer cells and a model of cervical LN-metastasis established by inoculating green fluorescent protein (GFP)-expressing cells into the tongue of nude mice. In both investigations, a few cancer cells were detected by real-time quantitative PCR, but not by conventional reverse transcription-PCR (RT-PCR). SCCA mRNA was detected at high levels in metastatic LNs. In contrast, 26 of the 30 control cervical LNs did not express the gene at all, and the rest showed fairly low levels. Of 108 histologically metastasis-negative LNs, 19 (17.6%) expressed SCCA mRNA levels higher than the cut-off value (1.0: mean expression of control LNs + 2SD). CK13 mRNA is not a suitable marker for the real-time PCR since it was detected frequently even in the control LNs. These findings suggest that genetic diagnosis by real-time quantitative PCR based on C SCCA mRNA expression may be clinically useful for detecting occult tumor cells in cervical LNs.

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記述言語：英語   出版者・発行元：KARGER  

Growth-regulated oncogene-1 (GRO-1) is an autocrine growth factor in melanoma and is a member of the CXC family of chemokines which promote chemotaxis of granulocytes and endothelia through binding to CXC receptor 2. A previous article noted that GRO-1 was upregulated in oral cancer using a genome-wide microarray approach. We have examined the expression of GRO-1 in 9 oral squamous cell carcinoma (OSCC) cell lines and 94 OSCC specimens. Using real-time quantitative polymerase chain reaction analyses, GRO-1 expressions were varied in OSCC cell lines. Of the 94 OSCC specimens, 37 (39.4%) showed GRO-1 cytoplasmic immunostaining, and microvessel density revealed a correlation between GRO-1 expression and tumor angiogenesis. GRO-1 expression was also associated with leukocyte infiltration, and lymph node metastasis. These findings suggest a possible relationship between the expression level of GRO-1 and tumor progression. Copyright (C) 2004 S. Karger AG, Basel.

DOI： 10.1159/000078333

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記述言語：英語   出版者・発行元：Scientific Communications International Ltd  

Objective: To evaluate the expression of HER2/neu in oral squamous cell carcinoma with a view to determining the usefulness of molecular target therapy by anti-HER2 antibody. Patients and Methods: Oral squamous cell carcinoma cell lines and 69 clinical tumour samples were tested using enzyme-linked immunosorbent assay and immunohistochemistry. Positive and negative controls were utilised. Results: Expression of HER2/neu in oral squamous cell carcinoma cell lines was low. Overexpression was not observed in the clinical samples. Conclusion: Low prevalence of expression of HER2/neu in oral squamous cell carcinoma limits the likely utility of herceptin therapy.

DOI： 10.1016/S0915-6992(04)80028-1

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DOI： 10.1016/S1368-8375(03)00127-1

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DOI： 10.1159/000074649

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. Recently, we have demonstrated that PPARgamma is expressed in human salivary gland tumors and its ligands inhibit the growth of cultured salivary gland cancer cells. However, expression and function of PPARgamma in normal and neoplastic human oral squamous epithelium remains unclear. in the present study, we examined PPARgamma expression in human oral squamous cell carcinoma (OSCC) and tested its ligands for any antitumor effect. PPARgamma mRNA was detected by RT-PCR in some OSCC tissues and cultured cells, but the PPARgamma protein showed neither expression nor ligand-induced transcriptional activity. Despite loss of PPARgamma function, synthetic PPARgamma ligands caused significant dose-dependent inhibition of cancer cell growth. These results suggest that PPARgamma function is inactivated in OSCC cells and the anti-proliferative effect of its synthetic ligands is independent of PPARgamma. (C) 2003 Elsevier Ltd. All rights reserved.

DOI： 10.1016/S1368-8375(03)00108-8

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記述言語：日本語   出版者・発行元：(一社)日本口腔腫瘍学会  

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記述言語：英語   出版者・発行元：PROFESSOR D A SPANDIDOS  

Hepatocyte growth factor (HGF) has been proposed to be an autocrine/paracrine growth factor for carcinomas of various organs. We recently demonstrated that HGF produced by prostate-derived stromal cells was a paracrine growth factor that stimulated the growth of androgen-independent prostate cancer cells in vitro and in vivo. To assess possible involvement of HGF in prostate cancer, we examined the immunohistochemical expression and localization of HGF and c-Met/HGF receptor in benign and malignant human prostate tissues. In benign glands, columnar cells generally were negative for c-Met, but basal cells were stained uniformly at a high level. In high-grade prostatic intraepithelial neoplasia (PIN) and carcinoma, more than 50% of these foci were stained uniformly. There was no difference in the frequency of positively stained cells by Gleason score. The prostate stroma stained diffusely for HGF, and the staining intensity varied depending upon the amounts of smooth-muscle cells that were stained more intensely than the connective-tissue matrix. A great majority of benign columnar cells were negative for HGF whereas high-grade PIN and carcinoma foci stained focally for HGF. Hormonal ablation therapy prior to prostatectomy did not seem to alter the expression of HGF/c-Met in carcinoma cells. These results indicate that, as the degree of neoplasia progresses, epithelial cells begin to express c-Met protein, that PIN and carcinoma may have developed a c-Met-HGF paracrine loop with the stroma, and that in some carcinoma foci an autocrine loop may operate with HGF expressed by carcinoma cells themselves.

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記述言語：日本語   出版者・発行元：日本癌学会  

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Flavopiridol is a synthetic flavone that inhibits tumor growth by suppressing cyclin-dependent kinases (CDKs). We have investigated effects of flavopiridol in oral squamous cell carcinoma (OSCC). Flavopiridol was found to inhibit the growth of OSCC cells in a time- and dose-dependent manner. Induction of apoptosis was observed in all cells showing accumulated cells with sub-G, DNA contents, DNA fragmentations, and PARP cleavages. While Bcl-2 and Bax expression did not change, Bcl-X-L was down regulated and Bcl-xs was up-regulated after being exposed to flavopiridol. Flavopiridol treatments also resulted in remarkable reductions of cyclin A, cyclin B, and cyclin D1 expressions. We also found that expression levels of CDK activation kinase and CDC25C were reduced, and p34 inactive form CDK2 were up-regulated. Our data indicate that flavopiridol has growth inhibition activities against OSCC. Flavopiridol not only inhibits CDKs directly, but it also inhibits the CDKs activation pathway and activates the Bcl-x apoptotic pathway. (C) 2002 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S1368-8375(02)00019-2

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記述言語：日本語   出版者・発行元：日本癌学会  

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記述言語：英語   出版者・発行元：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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記述言語：日本語   出版者・発行元：(公社)日本口腔外科学会