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ABSTRACT: Bcl-2 family proteins are regulators of programmed cell death and important in the development and progression of human various tumors. The role of these proteins in the development, progression and differentiation of esophageal squamous cell carcinoma (ESCC) is unclear.
We investigated the expression of Bcl-2, Bcl-X, and Bax using immunohistochemistry in 86 ESCCs, and scored the expression by the weighted score.
Bcl-2 expression related to pT category (P=0.043) and histological grade (P = 0.001). Bcl-X expression related to pT category (P = 0.003), pN category (P = 0.041) and the number of positive nodes (P = 0.036), and had a tendency to relate to histological grade (P = 0.086). Bax expression had a tendency to relate to pN category (P = 0.081). The inverse relationship between Bcl-2 and Bcl-X expression was detected (P = 0.001), while the positive one between Bcl-X and Bax expression was detected (P = 0.014). Patients with low Bcl-X weighted score had a significantly longer survival compared with those with high Bcl-X weighted score. Multivariate analysis revealed Bcl-X expression as the independent prognostic factors (P = 0.022).
These results imply that Bcl-2 family proteins, especially Bcl-X, may contribute to the progression in ESCC.
Journal of Surgical Oncology 11/2001; 78(2):116-23. · 2.10 Impact Factor
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ABSTRACT: Overexpression of annexin II, a calcium-dependent phospholipid-binding protein, has been reported in various carcinomas. One of its ligands is tenascin-C, an extracellular matrix glycoprotein with predominantly antiadhesive qualities that also has been reported to be a prognostic marker for several carcinomas. In the current study, the authors investigated the correlation between the overexpression of annexin II and tenascin-C in colorectal carcinoma.
Western blot analysis of annexin II expression was examined in four human colorectal carcinoma cell lines. Using immunohistochemical methods, the authors also examined expression of annexin II and tenascin-C in 105 primary colorectal carcinoma cases.
Although annexin II was expressed in human colon carcinoma cell lines, there was no apparent correlation between its expression level and the metastatic potential of these cell lines. The authors observed overexpression of annexin II and tenascin-C proteins in 29.5% and 49.5%, respectively, of colorectal carcinoma cases. Overexpression of annexin II was found to be correlated significantly with histologic type, tumor size, depth of invasion, and pTNM stage, whereas tenascin-C overexpression was noted to be correlated significantly with histologic type, depth of invasion, lymphatic invasion, venous invasion, lymph node metastasis, and pTNM stage. Expression of annexin II was shown to be correlated significantly with that of tenascin-C. Multivariate analysis demonstrated that annexin II and tenascin-C cooverexpression was an independent factor of poor prognosis in patients with colorectal carcinoma.
The data from the current study suggest that both annexin II and tenascin-C are overexpressed in advanced colorectal carcinoma and that they may be related to the progression and metastatic spread of colorectal carcinoma.
Cancer 10/2001; 92(6):1419-26. · 4.77 Impact Factor
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ABSTRACT: The role of splenectomy in the surgical management of gastric carcinoma is controversial and there is no consensus of opinion regarding the therapeutic value of splenectomy. The aim of this study was to search for possible metastasis to lymph nodes in the splenic hilum or along the splenic artery to avoid unnecessary splenectomy and to determine its indication.
The clinical records of 204 patients who underwent total gastrectomy combined with splenectomy for gastric carcinomas involving the proximal part of the stomach were analyzed.
The incidence of nodal involvement to the splenic hilum and/or along the splenic artery was 49 (24.0%) of 204 gastric carcinomas involving the proximal part of the stomach that underwent combined gastrectomy and splenectomy. The characteristics of gastric carcinoma with metastasis to these nodes included a larger tumor, deeper penetration (T3, 4 tumors), a number of lymph node metastasis, and infiltrative type. In T2 cases, all the tumors with cancerous involvement to these nodes showed intraoperative gross serosal change). When the tumor size was less than 40 mm, nodal metastatic rate to the splenic hilum and/or along the splenic artery was very low.
In conclusion, splenectomy should be conducted in T2 cases with gross serosal change and T3, 4 cases. With regard to tumor size, in the cases with a tumor whose size was less than 40 mm, it is possible to preserve the spleen in most cases. In the near future, splenectomy should be clarified precisely by randomized trials in advanced gastric carcinoma.
Hepato-gastroenterology 48(38):603-5. · 0.66 Impact Factor
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M Ueno,
F Koyama,
Y Yamada,
H Fujimoto,
T Takayama,
K Kamada,
A Naito,
S Hirao,
T Mukogawa,
H Hamada, Y Nakajima
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ABSTRACT: We studied the effect of suicide gene therapy using an adenovirus vector expressing the cytosine deaminase (CD) gene combined with irradiation therapy (chemo-radio-gene therapy) for human colorectal cancer cells. Since serum CEA levels are elevated in patients with some malignant tumors including colorectal cancer, we applied the CEA promoter to chemo-radio-gene therapy, expecting tumor-specific expression of the CD gene. In in vitro study, we succeeded in selective expression of the target CD gene and growth inhibition in only CEA-producing tumor cells; Further the inhibitory effect was enhanced by combination with radiation therapy in an irradiation dose-dependent manner. In addition, in in vivo study, a significant growth inhibition was observed in chemo-radio-gene therapy in comparison with radiation therapy alone or suicide gene therapy alone. Thus, we suggest that tumor-specific chemo-radio-gene therapy may be a useful strategy for human colorectal cancer.
Anticancer research 21(4A):2601-8. · 1.73 Impact Factor
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K Emoto,
H Sawada,
Y Yamada,
H Fujimoto,
Y Takahama,
M Ueno,
T Takayama,
H Uchida,
K Kamada,
A Naito,
S Hirao, Y Nakajima
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ABSTRACT: Annexins belong to a family of the calcium-dependent phospholipid binding proteins. They are also substrates of receptor tyrosine kinases. Overexpression of Annexin II, which has been reported in various carcinomas, is thought to be associated with cell proliferation, differentiation and cell-cell adhesion in the pathogenesis of carcinoma, but the functions of Annexins have not been fully elucidated. In this study, we investigated the role of Annexin II (p36) and its relationship with c-erbB-2 overexpression in gastric carcinoma. We studied Annexin II expression using Western blot analysis in 8 human gastric carcinoma cell lines and expression of Annexin II and c-erbB-2 using, immunohistochemistry in 153 primary gastric carcinomas. Western blot revealed that Annexin II was expressed in 8 human gastric carcinoma cell lines. It was more strongly expressed in the cell membrane than in the cytoplasm of tumor cells in primary gastric carcinoma tissues. Thirty-three percent of all cases were immunopositive for Annexin II, overexpression of which was more frequent in differentiated type (p = 0.0009), lymph node, metastasis (p = 0.0147) and venous invasion (p = 0.0092). Annexin II and c-erbB-2 overexpression were significantly correlated p = 0.0002) and patients with Annexin II had poorer prognoses (p = 0.0066). Multivariate analysis showed that immunopositivity of both Annexin II and c-erbB-2 was an independent and poor prognostic factor (p = 0.0037). In conclusion, Annexin II was overexpressed in advanced gastric carcinomas and it could contribute to the progression of gastric carcinoma.
Anticancer research 21(2B):1339-45. · 1.73 Impact Factor
