[Severe advanced lower gingival carcinoma effectively reduced by chemoradiation with S-1--report of a case].

Severe advanced head and neck carcinoma which can not be removed via surgical procedure combined with a large lymph node metastasis has a poor prognosis. We administered concurrent chemoradiotherapy with S-1 for a lower gingival carcinoma. As a direct result, we discovered that the treatment greatly reduced the size of tumor, and we consider that this treatment prolonged the patient.s life. The treatment results suggest that the so-called dormancy state of the tumor was continued. In this case study, radiotherapy with S-1 showed a highly effective response from the viewpoint of QOL improvement.

Changes of histological and biological features by serial passages in a human adenoid cystic carcinoma line transplantable in nude mice.

The basic histologic patterns of adenoid cystic carcinoma (ACC) are classified into three types (tubular, cribriform and solid), but clinical significance of the histological type is unclear. We have successfully established a human tumor line derived from ACC that is serially transplantable in nude mice. This tumor showed an increased growth rate as the passage levels proceeded, and the histological type was changed from a cribriform pattern in the initial stage to a solid one. In this study, we investigated the relationship between histological type and biological characteristics by analyzing the serially transplantable ACC tumor model. As a result, the tumor growth rate at the 15th passage level was increased approximately 5-fold compared with that at the initial passage level. In the histological type, approximately 30% of the cribriform pattern in the initial level was changed to a solid one at the 15th passage level, and the PCNA labeling index was elevated 4-fold. Concomitant with this, expression of Ki-67, p53 and bcl-2 proteins was increased, and apoptotic cells were decreased as demonstrated by the TUNEL method. From these findings, it was suggested that cell proliferation and histological change of this ACC tumor are related to the inhibition of apoptosis. This tumor line would provide a useful model for investigating the biological behavior of ACC.

Promotion of cell differentiation, and suppression of cell growth and cyclooxygenase-2 expression by differentiation-inducing agents in human oral squamous carcinoma SCC25 cells.

We investigated the relationship between cell growth and differentiation and COX-2 expression in oral squamous cell carcinoma (SCC) in vitro and in vivo. Treatment of SCC25 oral squamous carcinoma cells with sodium butyrate (SB) at 0.5-5 mM or all-trans retinoic acid (ATRA) at 3-300 microM inhibited cell growth and induced apoptosis in a dose-dependent manner with concomittant increases in expression of keratin 13, p21WAF1/Cip1 and p27Kip1 and decreases in expression of COX-2. These effects were more pronounced with SB than with ATRA. Injection of SB or ATRA near SCC25-derived tumors in nude mice resulted in inhibition of growth and elevation of differentiation of the tumor accompanied by marked keratinization and increased expression of keratin 13 and decreased expression of COX-2. These results show that the differentiation-inducing agents, particularly SB, suppress growth of oral squamous carcinoma cells through apoptosis and induce cell differentiation possibly through mechanisms involving COX-2, p27Kip1 and/or p21WAF1/Cip1 in vitro and in vivo.

Increased expression of cyclooxygenase (COX)-2 in DMBA-induced hamster cheek pouch carcinogenesis and chemopreventive effect of a selective COX-2 inhibitor celecoxib.

BACKGROUND: In recent years, overexpression of cyclooxygenase (COX)-2 protein and mRNA has been reported in various cancer tissues. Therefore, it has been suggested that COX-2 is related to carcinogenesis. METHODS: Hamsters were treated by painting a buccal pouch with a 0.5% DMBA solution dissolved in acetone. Basal diet or diets containing 150, 500 and 1500 ppm of celecoxib, a selective COX-2 inhibitor, were given ad libitum to hamsters, and tumor development was observed. RESULTS: Immunohistochemical and Western blot analyses revealed that COX-2 expression was increased toward the carcinogenesis. Although all hamsters developed squamous cell carcinoma, the onset of tumor formation was delayed in a dose-dependent manner. Also, tumor growth was retarded and survived animals were increased in the group of celecoxib treatment. Histologically, administration of celecoxib increased the apoptotic cells in the tumor parenchyma and significantly inhibited the angiogenesis in the stroma. CONCLUSIONS: The COX-2 expression was increased during hamster cheek pouch chemical carcinogenesis. Administration of celecoxib demonstrated the chemopreventive potential against the carcinogenesis.

Apoptosis induction and enhancement of cytotoxicity of anticancer drugs by celecoxib, a selective cyclooxygenase-2 inhibitor, in human head and neck carcinoma cell lines.

Colorectal carcinomas are well known to highly express COX-2 and their growth is markedly inhibited by COX-2 inhibitors, but little is known about head and neck carcinomas. In this study, we investigated the effect of a selective COX-2 inhibitor, celecoxib, on growth and apoptosis induction of four human head and neck carcinoma cell lines, SCC25, KB, HSG and HSY, in comparison with frequently used COX inhibitor sulindac. Also, we examined whether celecoxib augments the sensitivity of these cell lines to anticancer drugs such as doxorubicin (DOX), vincristine (VCR), cisplatin (CDDP), bleomycin (BLM) and 5-fluorouracil (5-FU). The growth of all cultured cell lines particularly SCC25 and HSG was inhibited by celecoxib and sulindac in a dose-dependent manner. The IC50 of celecoxib was ten times lower than that of sulindac. SCC25 produced ample PGE2 whereas KB, HSG and HSY produced a small amount of PGE2. The PGE2 production and COX-2 expression were inhibited more efficiently by celecoxib than by sulindac. Exogenous addition of PGE2 resulted in an increased cell growth of SCC25 even under the celecoxib-treated condition, but not of HSG. These results suggested that PGE2 is involved in the growth of SCC25 but not of HSG. The ability of celecoxib to induce apoptosis is greater than that of sulindac. Treatment of SCC25 and HSG with non-cytotoxic 1 micro M or less cytotoxic 5 micro M of celecoxib enhanced the sensitivity of both cell lines to anticancer drugs, particularly in DOX, VCR and BLM two to ten times as demonstrated by lowering of IC50s. The enhanced rate was almost parallel to the degree of apoptosis induction. These findings indicated that a selective COX-2 inhibitor celecoxib inhibits cell proliferation, induces apoptosis and augments sensitivity to anticancer drugs in human head and neck carcinoma cells. Therefore, celecoxib would be useful as biological modulator in treatment of head and neck cancer.

Small cell neuroendocrine carcinoma of the maxillary sinus--a case report and nude mouse transplantable model.

BACKGROUND: A rare case of small cell neuroendocrine carcinoma (SNEC) arising in the maxillary sinus is presented, and a SNEC tumor line serially transplantable in nude mice was established. Tumor marker for SNEC is also discussed. METHODS: The tumor tissues obtained from operated material were heterotransplanted subcutaneously into nude mice. Histopathologic studies and immunoradiometric assays for NSE and pro-GRP in serum were performed. RESULTS: The primary lesion was composed of tumor nests of small cells with hyperchromatic nuclei and was positive for NSE and chromogranin A immunohistochemically. Serum levels of NSE and pro-GRP changed dynamically, reflecting the clinical status. Nude mouse tumor showed similar histologic features to those of original tumor and expressed NSE. Neuroendocrine granules were detected in tumor cells in electron microscopy. Serum NSE level in nude mice was elevated in proportion to the relative tumor weight. CONCLUSIONS: Serum NSE and pro-GRP were useful tumor markers for extrapulmonary SNEC. A SNEC tumor transplantable in nude mice would provide a valuable model for characterization of this lesion.

[Treatment of hypercalcemia of malignancy with pamidronate in a patient with advanced recurrent oral cancer].

Hypercalcemia of malignancy is a common problem for cancer clinicians. Treatment of hypercalcemia of malignancy with pamidronate in a patient with advanced recurrent oral cancer is reported herein. The patient was a 36-year-old man who had neck lymph node metastases due to recurrence of squamous cell carcinoma of the buccal mucosa and complained of cloudiness of consciousness due to hypercalcemia. The patient was administered pamidronate. A fine reduction in serum calcium was observed and cloudiness of consciousness was also alleviated. Although treatment of hypercalcemia with pamidronate is palliative, it is effective against the deterioration of quality of life.