Goichi Tsukamoto

Expression of vascular endothelial growth factor-C predicts regional lymph node metastasis in early oral squamous cell carcinoma.

The purpose of this study was to investigate the association of the expression of vascular endothelial growth factor-C (VEGF-C) with regional lymph node metastasis in oral squamous cell carcinoma (OSCC). The expression of VEGF-C in biopsy specimens obtained from 62 patients with OSCC was examined by immunohistochemistry. In the early stages of T1 and T2 (38 cases), VEGF-C expression strongly correlated with lymph node metastasis (P < 0.001), and the percentage of VEGF-C-positive staining was 88.2% for patients with lymph node metastasis (15 of 17 cases) and 28.6% for those without lymph node metastasis (6 of 21 cases). However, in the advanced stages of T3 and T4, no significant correlation between VEGF-C expression and lymph node metastasis was observed. These results indicate that VEGF-C expression in biopsy specimens can be used as a reliable predictor of regional lymph node metastasis, particularly in early OSCC, and may become an important factor in the selection of appropriate treatment.

Area postrema mediates gastric motor response induced by apomorphine in rats

The effects of apomorphine administration on the autonomic responses were investigated in rats. Distinctive gastric motor responses were observed after the intravenous administration of apomorphine (0.1 mg/kg body weight). Gastric motor responses in the distal stomach induced by apomorphine administration were classified into two types. One type involved inhibition of phasic contractions which appeared just after the administration of apomorphine. The other involved an increase in the frequency of small phasic contractions accompanied by increased gastric tone appearing with a relatively longer delay. No relaxation was observed in either the proximal or distal stomach. These gastric motor responses showed a dose-response effect to the amount of apomorphine administered (0.002-0.1 mg/kg body weight). In addition, submandibular salivary secretion was observed in response to the intravenous administration of apomorphine at a dose of 3 or 10 mg/kg body weight. Pretreatment with domperidone (1 or 2 mg/kg body weight) or the ablation of the area postrema (AP) abolished the gastric motor response and salivary secretion induced by the administration of apomorphine. In conclusion, rats showed definitive autonomic phenomena in response to the administration of apomorphine. Dopamine 2-like receptors situated in the AP mediate apomorphine-induced autonomic phenomena in rats.

Abdominal vagi mediate c-Fos expression induced by X-ray irradiation in the nucleus tractus solitarii of the rat

The mechanism of induction of emesis by X-ray irradiation remains largely unknown. The purpose of the present research was to clarify the neuronal basis of the induction of nausea induced by X-ray irradiation analyzing c-Fos expression in the nucleus tractus solitarii (NTS) as a marker of cellular excitation. We confirmed that the dose of X-ray irradiation (4 Gy) used for the present research could actually induce nausea by preliminary measurement of kaolin intake. Induction of c-Fos immunoreactivity in the NTS was observed in the animals that received X-ray irradiation of the whole body. The mean number of c-Fos positive cells in the animals that received irradiation was significantly larger than that in the non-irradiated animals. Partial exposure of the abdomen to X-rays showed significantly greater c-Fos expression than that of the head. These results indicated the presence of a certain route for transmitting information from the periphery toward the central nervous system by X-ray irradiation. The number of c-Fos positive cells induced by X-ray irradiation in animals vagotomized at the subdiaphragmatic level was lower than that in sham-operated animals. Animals receiving a serotonin subtype three (5-HT3, 5-hydroxytryptamine) receptor antagonist (tropisetron, ICS 205-930, 3-tropanyl-indole-3-carboxylate) showed a significant reduction in c-Fos protein expression compared to animals receiving a vehicle. These results strongly suggested that X-ray irradiation activates 5-HT3 receptors on the terminals of the abdominal vagal nerves to excite the afferent pathway, thereby inducing emesis.

Identification of CCDC62-2 as a novel cancer/testis antigen and its immunogenicity

Cancer/testis (CT) antigens are expressed in normal germ line tissues and various cancers. They are considered promising target molecules for immunotherapy for patients with various cancers. To identify CT antigens, we performed serological identification of antigens by recombinant expression cloning. The humoral immune response of cancer patients against a newly defined antigen was analyzed. A testicular cDNA library was immunoscreened with serum obtained from a gastric adenocarcinoma patient whose primary cancer had regressed once and most liver metastasies had disappeared transiently. We isolated 55 positive cDNA clones comprising 23 different genes. They included 4 genes with testis‐specific expression profiles in the Unigene database, including coiled‐coil domain containing 62 (CCDC62). RT‐PCR analysis showed that the expression of 2 splice variants of CCDC62 was restricted to the testis in normal adult tissues. In malignant tissues, CCDC62 variant 2 (CCDC62‐2) was aberrantly expressed in a variety of cancers, including stomach cancer. A serological survey of 191 cancer patients with a range of different cancers by ELISA revealed antibodies to CCDC62‐2 in 13 patients, including stomach cancer. None of the 41 healthy donor serum samples were reactive in the same test. The serum reaction against CCDC62‐2 was confirmed by western blot. CCDC62‐2 is a CT antigen that is immunogenic in cancer patients.

A spindle cell carcinoma presenting with osseous metaplasia in the gingiva: a case report with immunohistochemical analysis

BackgroundSpindle cell carcinoma (SpCC) is a rare, high malignant variant of squamous cell carcinoma (SCC), which shows biphasic proliferation of conventional SCC component and malignant spindle shape cells with sarcomatous appearance.MethodsA case of Spindle cell carcinoma with bone-like calcified materials, occurring at the mandibular molar region of 71-years-old Japanese male patient was presented with gross finding, histological findings and MRI image. To identify the characteristics of the bone-like materials, immunohistochemistry were performed.ResultsHistologically, the cancer cells were composed of spindle cells and epithelial cells which form nests with prominent keratinization. Histological findings showed typical histology of the SpCC, however, as an uncommon finding, spatters of calcified, bone-like materials were observed in between the cancer cells. Immunohistochemistry revealed that cancer cells were positive for cytokeratins and vimentin to a varying degree and negative for Desmin, S-100, Osteopontin, BMP-2 or BMP-4. These findings implied that the calcified materials were formed by metaplasia of the stromal cells.DiscussionBone-like materials formation by osseous and/or cartilaginous metaplasia of the stroma in the carcinoma has been reported. However, the detailed mechanism of these metaplasia and affection on the clinical feature, prognosis and therapies are not well established. In summary, we presented an unique case of SpCC, which has not been described in the literature.

Protective effect of cepharanthin on cisplatin-induced renal toxicity through metallothionein expression.

AIMS Cisplatin (CDDP) is a potent anticancer agent, but severe renal toxicity can limit its use. We investigated the protective effect of cepharanthin (CE), a biscoclaurin alkaloid, on the renal toxicity of CDDP. MAIN METHODS Mice were given CDDP along with CE. Effects of CE on CDDP toxicity were investigated by assaying markers of renal toxicity together with MT expression, and by histopathological examination of the kidney. MT-null mice were also examined. KEY FINDINGS CE induced expression of metallothionein (MT). Pre-administration of CE attenuated an increase in blood urea nitrogen (BUN) concentrations after the CDDP injection. A histochemical analysis demonstrated protection against CDDP-induced necrocytosis of kidney tissues by CE. The protective effect of CE did not occur in the MT-null mice. SIGNIFICANCE Pretreatment with CE may reduce the renal toxicity of CDDP through expression of MT.

Cisplatin-induced long-term dynorphin A-immunoreactivity in cell somata of rat area postrema neurons

We evaluated long-term dynorphin A-immunoreactivity in the rat area postrema (AP) after the administration of cisplatin. First, rats were given 1, 5 and 10mg/kg body weight cisplatin (i.p.) and their behavior was monitored for 72h. We observed a delayed increase in pica 24-72h after injection, compared to the 24h before injection. We attributed this to the cisplatin injection. Pica was defined as an increase in the intake of non-nutritional matter such as kaolin. Administration of 1, 5 and 10mg/kg cisplatin led to an increase in kaolin intake on day 1. Administration of 5 and 10mg/kg of cisplatin led to decreased intake of laboratory chow (MF) on days 1-3, but 10mg/kg cisplatin causes an excessive aggravation of their condition. Following this behavioral experiment, we immunohistochemically examined the induction of dynorphin A in the AP at 24, 48 and 72h post-administration of 1 and 5mg/kg cisplatin. Administration of 5mg/kg cisplatin caused dynorphin A to accumulate gradually in the neurosoma of the AP neurons, and the numbers of positive AP neurosomata at 48 and 72h post-administration were higher than following an equal dosage of 0.9% NaCl. These findings suggest that dynorphin A increases in the central nervous system for a long time following administration, and causes certain behavioral and clinical changes, including those related to appetite and nausea.

Atypical Simple Bone Cyst of the Jaws — Multiple Cysts and Repeated Recurrence

Abstract This report is of a patient with unusual multiple simple bone cysts. A 17-year-old Japanese man presented with 3 cystic lesions, 2 in the mandible and 1 in the left maxillary sinus. Biopsies from the mandible revealed fibrous tissue, bone, and red blood cells, which did not suggest any specific lesion. A diagnosis of multiple simple bone cysts was made. After treatment of surgical exploration, curettage, and packing, computed tomography scan showed bone regeneration. However, the lesions repeatedly recurred in the mandible. It is generally thought that the prognosis of this lesion is good. Therefore the cause of this recurrence is examined.

Clinical analysis of four cases of oral malignant melanoma.

岡山大学歯学部附属病院第二口腔外科にて加療した口腔悪性黒色腫4例について臨床的検討を行った。対象症例の性別は男性2例, 女性2例, 年齢は57歳から75歳までであった。原発部位は下顎歯肉1例, 口蓋3例で初診時のUICC (1997) 分類はstage Ia期: 1例, stage II期: 1例, stage III: 2例であった。治療法は全例外科療法を施行し, 化学療法及び免疫療法またはホルモン療法を併用した。局所再発及び頸部リンパ節転移または遠隔転移をきたした2例が死亡例であった。他の2例は, 局所再発及び転移はなく, 経過観察期間は14年11ケ月と3年8ケ月であった。

Clinico-statistical analysis of mucoepidermoid carcinoma.

1982年4月より1999年3月までに岡山大学歯学部附属病院第二口腔外科を受診し, 病理組織学的に粘表皮癌と診断された27例について臨床統計的検討を行ったので報告する。 (1) 性別発生頻度は, 男性16例, 女性11例。 (2) 年齢別発生頻度は平均63.0歳であった。 (3) 部位別発生頻度をみると大唾液腺2例, 小唾液腺25例。 (4) TNM分類ではT1が7例, T2が7例, T4が13例であり, Stage別では, Stage Iが7例, Stage IIが7例, Stage IVが13例であった。 (5) 治療法については, 24例に対して外科療法を施行し, そのうち外科療法の単独施行は13例, 化学療法および放射線療法の併用療法を施行したものは11例であった。 (6) 全体の5年累積生存率は69.4%で, Stage I, II症例が90.9%, Stage IV症例が46.4%であった。