| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
1).To evaluate the potential of interleukin 12 (IL-12) in combination with interleukin 2 (IL-2) as an inducer of enhanced-killer cells against human tumors in in vitro system, PBL from cancer patients (n=15) were cultivated with IL-2 or IL-12/IL-2 for 10 days (LAK generation), and PBL from cancer patients (n=16) were also stimulated with MMC-treated allogeneic tumor cells for 3 days, followed by further cultivation with IL-2 or IL-12/IL-2 for 7 days (CTL generation). The cytolytic activities of the cells cultured with IL-12/IL-2 combination were significantly increased as compared with those of IL-2 alone in both LAK and CTL generation systems (p<0.01). In LAK generation system, IL-12/IL-2 induced killer-effector cells showed NK cell type bearing CD8-CD11b+, CD8-CD16b+ and CD3-CD56+. While, in CTL generation systems, CD8+CD11b-T cells mixed with NK cell type bearing CD8-CD11b+, CD8-CD16b+ and CD3-CD56+ were cell population of killer-effector cells induced by IL-12/IL-2 combination.
2).E
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xpression of costimulatroy molecules, such as B7-1 (CD80 antigen) and B7-2 (CD86 antigen) was determined in carcinoma of the primary focus in the stomach (10 cases) and the esophagus (3 cases), and in carcinoma of the metastatic lesion in the malignant ascites (5 cases) by the method of two-color flow cytometry. Also, gastric normal mucosa (14 cases) was made to examine as a control. As a results, the mean positive rate of CD80 antigen-expression of normal gastric mucosa and the primary lesion of the stomach and the esophagus shows 50.1% and 43.8%, respectively. While, the mean positive rate of the metastatic lesion shows lower levels, revealing 11.8%. The CD86 antigen-expression of normal mucosa, primary and metastatic lesions shows 56.4%, 68.8% and 76.1%, respectively. Thus, CD86 antigen may be expressed on tumor cells at higher levels in accordance with cancer proliferation and metastasis. Lower level of expression of CD80 molecule on tumor cells, especially metastatic lesion results in inadequate B7-1 costimulation. This may contribute to the escape of tumors from destruction by the host's immune system.
3).Adenocarcinoma cells of the stomach showed intense immunoreactivity with both anti TGF alpha and anti EGF receptor antibodies. Coexpression of TGF alpha and EGFR in the tumor suggests an aberrant autocrine loop for autostimulation, which may play an important role in the further progression of gastric carcinoma toward invasive tumor growth and metastatic potential. EGFR expression was also noted on the paillomatous hyperplasia of the cutaneous verrucous papules lesion. Serum level of TGF alpha, determined by an ELISA was high 144 pg/ml (normal 22.0 <plus-minus> 16 pg/ml). Serum TGF alpha abruptly decreased to 49 pg/ml on day 7 after the total gastrectomy. Amelioration of the cutaneous lesions was observed after surgical resection of the gastric carcinoma. This suggests that TGF alpha stimulates the proliferation of keratinocytes involved with EGFG.Large amounts of circulating TGF alpha in the blood over a long period released by the primary tumor seem to act as an endocrine-like mechanism causing epidermal cells to proliferat Less
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