1.An Adenoid Cystic Carcinoma Cell Line Possessing High Metastatic Activity has High NF-κB Activation in Response to TNF-α
Katsuhiro Seki ; Kotaro Ishii ; Tsuyoshi Sugiura ; Miho Takahashi ; Yoshiko Inoue ; Kanemitsu Shirasuna
Oral Science International 2005;2(1):36-44
Adenoid cystic carcinoma (AdCC) is characterized by frequent recurrence and distant metastasis. Although lung metastasis in AdCC is very common, the mechanism by which this occurs is uncertain. When five AdCC cell lines (ACCS, ACCT, ACCH, Acc-3, and Acc-M) were screened for metastatic ability by injecting tumor cells into nude mice via the tail vein, lung metastases were found in mice injected with Acc-M (15/16 mice) but not in mice injected with any of the other four cell lines (0/10 mice with each line). To determine why Acc-M metastasizes to the lung but the others do not, we examined the biological characteristics of Acc-M and compared them with those of the other lines.Nuclear factor-κB (NF-κB) may play a key role in malignant tumor behaviors such as invasion and metastasis. Thus, we examined these cell lines for response to tumor necrosis factor (TNF-α), one of the typical stimulators of NF-κB. Although treatment with TNF-α stimulated matrix metalloprotease 9 (MMP-9) expression in all cell lines, the response to TNF-α varied between cell lines; the greatest stimulation was observed in Acc-M. Acc-M expressed higher levels of TNF receptors (both TNF-R1 and TNF-R2) than did the other AdCC lines. Judging from inhibitor-κBα degradation and nuclear translocation and DNA binding by NF-κB, the degree of activation of NF-κB in response to TNF-α in Acc-M cell lines was very high compared to the other lines. Moreover, the ability of Acc-M cells to adhere to endothelial cells, which was greater than that of the other cell lines, was further enhanced by pretreatment with TNF-α. Acc-M cells also expressed higher levels of sialyl Lewisx than did the other AdCC cell lines. These findings suggest that lung metastasis is mediated by tumor-endothelial cell interaction, which is probably associated with the NF-κB activation pathway. Further experiments are required to identify the molecules that mediate both lung metastasis and NF-κB activation.
2.Expression of Urokinase-type Plasminogen Activator (uPA), uPA Receptor, and Plasminogen Activator Inhibitor-1 in Oral Squamous Cell Carcinoma
Yoshiko Inoue ; Tsuyoshi Sugiura ; Ryousuke Matsuki ; Kotaro Ishii ; Katsuhiro Seki ; Kanemitsu Shirasuna
Oral Science International 2007;4(1):38-44
We investigated whether the expression levels of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1) correlate with clinicopathological features of oral squamous cell carcinoma (SCC). We immunohistochemically examined the expression levels of uPA, uPAR, and PAI-1 in 160 biopsy specimens of oral SCC. Positive stainings for uPA, uPAR, and PAI-1 were observed mainly in SCC cells, and their intensity and number of positive cells were related to lymph node involvement (p < 0.001, p < 0.001, and p < 0.001, respectively). The expression levels of uPA and uPAR were also related to the pattern of invasion (p < 0.05 and p < 0.001, respectively), while both were associated with tumor size (p < 0.05). Moreover, a poor survival rate was related to the expression of uPAR (p < 0.01) and PAI-1 (p < 0.05). These findings suggest that the uPA system may regulate the invasion and metastasis of oral SCC cells.
3.Results of gastric mass survey in Tsuchiura Kyodo Hospital.
Katsuhiro Sanada ; Mamoru Takeshi ; Koji Koike ; Kazuo Hirose ; Koichi Matsuda ; Yoshio Ishida ; Yoji Nakazawa ; Masahiro Tsubaki ; Tomoyuki Suzuki ; Kazushi Seki ; Susumu Hiranuma ; Koichi Shibata ; Kohei Okamoto ; Shin Tonouchi
Journal of the Japanese Association of Rural Medicine 1985;33(5):907-912
We began gastric mass survey at our hospital in May, 1980. During 3 years and 8 months since then, (May, 1980-December, 1983) we performed screening examinations to 16, 341 people by indirect radiography, and checked 2, 824 cases (17.3%) for thorough examination. Among these cases, 2, 083 (73.8%) received endoscopic examination actually, and 55 cases of gastric cancer were discovered. The discovery rate of gastric cancer was 0.336 per cent.
35 cases of these 55 gastric cancer were operated in the surgical department of our hospital. 34 cases were resected (rate of resection was 97.1%) and 33 cases were resected curatively (rate of curative resection was 94.3%). These results were better than that of gastric cancer cases from out-patient clinic of the same period. The results of cases from out-patient clinic of our hospital were: total number of cases 321, resected cases 254 (79.1%), curative resection 189 cases (58.9%), respectively.
4.Clinical studies of gastric cancer cases at a rural hospital in southern district of Ibaraki Prefecture.
Katsuhiro SANADA ; Kohei OKAMOTO ; Koichi SHIBATA ; Susumu HIRANUMA ; Kazushi SEKI ; Noriaki TAKIGUCHI ; Itaru TAKASHIMA ; Norihide SUGANO ; Hiroyuki KOBAYASHI ; Tetsujin KURE ; Shin TONOUCHI
Journal of the Japanese Association of Rural Medicine 1991;39(5):1018-1030
During the eleven years from January 1978 to December 1988, we experienced 1, 287 cases of gastric cancer, hospitalized in the surgical department of Tsuchiura Kyodo Hospital which is located in the southern agricultural district of Ibaraki Prefecture.
Among these 1, 287 cases, 1, 233 patients were operated on. Gastric resection was performed in 1, 059 cases including 337 cases of total gastrectomy with the resection rate of 85.9 percent (1, 059/1, 233). In 863 cases, resection gave histologically satisfactory results, and our curative resection rate was 70.0 percent (863/1, 233). Direct mortality rate was 2.35% in all operated cases and 1.32% in resected cases.
The five-year survival rate over the period from 1978 to 1983 was 57.7% in all resected cases and 69.3% in curatively resected cases.
Annual follow up observation showed increases in resection rate, curative resection rate, and five-year survival rate. However, there were no remarkable changes in the rate of total gastrectomy, rate of combined resection of other organs, and degree of lymph nodes dissection.
The main factor contributing to the improvement in the results of surgical treatment of gastric cancer was the increase in the detection rate of cancer in relatively early stages, through gastric mass survey or total check-up in the asymptomatic stage.