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 metastases 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.

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.

An immunohistochemical evaluation of BMP-2, -4, osteopontin, osteocalcin and PCNA between ossifying fibromas of the jaws and peripheral cemento-ossifying fibromas on the gingiva.

The present study examined histological difference between ossifying fibromas (OF, n=5) and peripheral cemento-ossifying fibromas (PCOF, n=7). Bone morphogenetic proteins (BMP)-2 and -4, osteopontin (OPN), osteocalcin (OCN) and proliferating cell nuclear antigen (PCNA) were used for the immunohistochemical examinations. Oxytalan fibers present at the periodontal tissue were stained to determine the tumor cell origin. Many OFs showed high immunohistochemical reactions for BMP-2, -4 and OPN compared to those of PCOFs. PCNA index (IP) of OFs was significantly higher than that of PCOFs. All the PCOFs showed a high expression of oxytalan fibers. Only two OFs exhibited a small number of oxytalan fibers. These results suggest that PCOF has only little ability to form hard tissue and seems to be a reactive lesion. The expression of oxytalan fibers reveals that OF does not only originate from periodontal tissue.

[A successful case of lower gingival cancer with pulmonary metastases by adjuvant chemotherapy including paclitaxel, cisplatin and 5-fluorouracil following a surgical procedure].

We report a successful case with pulmonary metastases from lower gingival cancer by a surgical procedure and four cycles of adjuvant chemotherapy including paclitaxel (PTX), cisplatin (CDDP) and 5-fluorouracil (5-FU). A 47-year-old woman underwent chemotherapy with CDDP and 5-FU after an operation for lower gingival squamous cell carcinoma and its neck lymph node metastases. At 4 months from the initial treatment, pulmonary metastatic lesion was resected by video-assisted thoracoscopic surgery (VATS). Fourteen months later, pulmonary metastatic lesion was found and dissected again using VATS. Furthermore, the patient was treated by adjuvant chemotherapy with PTX 135 mg/m(2) over 3 hours on day 1, CDDP 75 mg/m(2)on day 2 and 5-FU 350 mg/m(2)/day by continuous intravenous infusion on day 2 through 5. After that, there is no evidence of pulmonary recurrence for more than six years.

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.

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.

A comparative study of odontogenic keratocysts associated with and not associated with an impacted mandibular third molar.

OBJECTIVE: The purpose of this study was to compare odontogenic keratocysts associated with and not associated with an impacted mandibular third molar. STUDY DESIGN: Panoramic radiographs of odontogenic keratocysts associated with impacted mandibular third molars (15 cysts, associated group) were compared with radiographs of odontogenic keratocysts not associated with impacted mandibular third molars (25 cysts, nonassociated group). The radiographic images were analyzed with reference to the patients' age and sex. RESULTS: The mean age of patients in the associated group was lower than that of patients in the nonassociated group. The mean area of the cysts in the associated group was larger than that of those in the nonassociated group. The patients' ages did not significantly correlate to the areas of either kind of cyst. CONCLUSIONS: The odontogenic keratocysts in the associated group had a tendency toward rapid growth in the patients' youth.

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.

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

BACKGROUND: Spindle 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. METHODS: A 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. RESULTS: Histologically, 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. DISCUSSION: Bone-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.