Shigehiro Kumagai

Immunohistochemical study of tumour angiogenesis in oral squamous cell carcinoma

To assess the clinical significance of angiogenesis in oral squamous cell carcinoma (SCC), we examined vessel density immunohistochemically in 44 primary oral SCCs using the JC-70A antibody which reacts specifically with vascular endothelial cells. In addition, the expression of vascular endothelial growth factor (VEGF) and its receptors, KDR, Flt-1 and Flt-4 in oral SCCs was examined in relation to the vessel density and lymph node metastasis. There was no association of vessel density with tumour site, T-category (tumour size), degree of differentiation or cervical lymph node metastasis, except that the vessel density of carcinomas with a well-defined tumour-stromal boundary was higher than that of diffusely invasive carcinomas. The intensity of VEGF expression correlated with lymph node metastasis (P < 0.01), but not with vessel density. The expression of KDR and Flt-1 did not correlate with vessel density and lymph node metastasis. However, the vessel density in Flt-4-positive carcinomas was higher than that in Flt-4-negative carcinomas (P < 0.05), and expression of Flt-4 most significantly correlated with lymph node metastasis (P < 0.001). These results suggest that the expression of VEGF or Flt-4 rather than vessel density may be a predictor of lymph node metastasis in oral SCC.

Development of a new invasion and metastasis model of human oral squamous cell carcinomas.

A new model was devised in order to establish an in vivo model for oral carcinoma that exhibits significant local invasion and metastasis. One hundred and fifty-two nude mice had tumour cells from one of two established oral squamous cell carcinoma (SCC) cell lines (OSC-19 and OSC-20) implanted into the tongue or the oral floor via an intra-oral route and, as a control, the subcutaneous tissue of the back. The back tumours showed an expansive growth pattern, lacking significant invasion of surrounding tissues. In contrast, the tumours implanted into the tongue or the oral floor exhibited invasive growth and the histological appearance was similar to that of the original tumours. Moreover, regional neck lymph node and pulmonary metastases were observed in this model. Regional neck lymph node metastases were detected in 81.0% of mice implanted with OSC-19 cells and in 13.6% of mice implanted with OSC-20 cells. OSC-19 and OSC-20 cells showed pulmonary metastases in 9.5 and 9.1% of mice, respectively. These results suggest that this intra-oral implantation model is valuable in the study of the mechanism of invasion and metastasis of oral SCC.

Inhibitory effects of adhesion oligopeptides on the invasion of squamous carcinoma cells with special reference to implication of αv integrins

We studied invasion-related adhesion events in vitro using three squamous carcinoma cell lines (HSC-3, poorly differentiated type; OSC-19, well-differentiated type; and KB cells, undifferentiated type). An in vitro invasion assay through matrigel in the transwell chamber revealed that HSC-3 cells were most invasive, OSC-19 cells moderately invasive and KB cells least invasive. Inhibition assay of invasion using synthetic peptides RGD, RGDV, RGDS, RGDT, IKVAV and YIGSR, showed that invasion of the three cell lines was significantly inhibited by RGDV. There were other peptides that inhibited invasion significantly including IKVAV for HSC-3, and RGDS and YIGSR for OSC-19. HSC-3 cells and OSC-19 cells adhered to fibronectin, laminin, vitronectin, and type IV collagen, and KB cells did not adhere to laminin but did to fibronectin, vitronectin and collagen type IV. Pretreatment of cells with RGDV peptide in the attachment assay reduced the ability of these cells to bind to vitronectin and fibronectin more efficiently than pretreatment with RGDS. Anti-αv antibodies inhibited adhesion of HSC-3, OSC-19 and KB cells to vitronectin, but anti-β1 antibodies did not inhibit adhesion. Immunofluorescent microscopic examinations showed that all cell lines were positive for anti-β5 and anti-αv antibodies, and only HSC-3 cells were positive for anti-β3 antibody. α5β1 was not clearly demonstrated in any of the cell lines. RGDV was the most effective inhibitor of squamous cell carcinoma invasion among the synthetic oligopeptides used in this experiment, and it is suggested that it affects αvβ3-and/or αvβ5-mediated carcinoma cell invasion.

Changes in work performances in obstructive sleep apnea patients after dental appliance therapy

Abstract The effects of dental appliances on work performances of obstructive sleep apnea syndrome (OSAS) is not well examined. This study evaluated the polysomnographic and psychological findings before and after therapy. Nine patients were diagnosed OSAS by nocturnal polysomnography. The psychological battery was performed from 13:00 to 14:00, which consisted of Uchida‐Kraepelin psychodiagnostic test (U‐Ks test) and Bourdons cancellation test (Bourdons test). Approximately 3 months after the treatment, the examinations were performed. Apnea and desaturation index decreased significantly after the therapy. In addition, sleep architecture improved after the therapy compared with that before the therapy. Dysfunction of task performances, such as mean level of work amounts in U‐Ks test, mean error, mean performance time and mean deviation in Bourdons test improved after therapy. We conclude that dental appliances therapy is effective not only to apnea but also to work performance in OSAS.

A case of upper gingival carcinoma with secondary neck metastasis occurring three years and eleven months after primary tumor resection.

口腔扁平上皮癌における後発頸部転移の発現時期は大部分が1年以内である。われわれは, 上顎歯肉癌の原発巣切除後3年11か月経過した後に後発転移をきたした稀な症例を経験したのでここに報告した。患者は67歳の男性で, その左側上顎歯肉部の扁平上皮癌 (T1N0M0) に対し, 術前化学療法と腫瘍の局所切除を初回治療として行った。初回治療終了後3年11か月経過後に左側頚部に転移性腫瘍が発現した。そこで, 直ちに左側頸部の根治的郭清術を行ったが, その後頸部腫瘍が再発し, 最終的に患者を救命することはできなかった。組織学的検査の結果では, 原発腫瘍および頸部転移腫瘍は山本・小浜分類の癌浸潤様式4D型を呈していた。頸部転移の発現がこのように遅れたのは, リンパ節内の癌細胞が長い間“静止状態”にあり, その後突然, 増殖が活発になったためと考えられる。本症例の臨床経過を考慮すると, 4D型腫瘍に対する予防的頚部郭清の必要性があらためて認識された。

Seven cases of carcinoma of the upper gum seemed to be related to the use of dentures.

1978年から1992年までの過去15年間に当科で治療を行った上顎歯肉扁平上皮癌患者は14例であった。そのうち, 腫瘍の発生部位, 義歯との位置的関係および義歯の装用状況の観点から, 癌発症に義歯の関与が示唆された7症例を対象とし, これらの臨床病理学的検討を行った。対象患者は男性2例, 女性5例であり男女比は1: 2.5であった。67歳から94歳にわたり平均年齢は79歳であり7例中6例が70歳以上であった。腫瘍は片側の臼歯部, 口蓋部, 上顎結節の義歯床下より発生した。無痛性の主訴が多く, 初診時すでに進展していた症例も多かった。しかし, すべて外向性発育を呈し, 所属リンパ節転移や遠隔転移は認められなかった。また組織学的には低悪性度と考えられる分化型扁平上皮癌であった。義歯の装用期間は長年にわたり, 夜間就寝時もほとんどはずすことなく装用した。これらより, 長期にわたる義歯の不適切な使用が発癌に関与していることが示唆された。