[Basic studies on IL-2 gene therapy for head and neck carcinoma].

Basic studies on transduction of the interleukin-2 (IL-2) gene into tumor cells were carried out in order to develop a new immunotherapy for head and neck carcinomas. We transduced the IL-2 gene into KB cells using defective herpes simplex viral (HSV) amplicon vector as the gene transfer vehicle. A high level of IL-2 was produced by IL-2 gene transduced KB cells (KB/IL-2). Human peripheral blood mononuclear cells (PBMC) cultured in medium containing the culture supernatant of KB/IL-2 cells showed stronger cytotoxic activity against KB cells than the control. In in vivo studies, high levels of IL-2 and interferon-gamma (IFN-gamma) were detected in the serum of nude mice transplanted with KB/IL-2 cells. The spleen cells of KB/IL-2 cell-transplanted nude mice exhibited high cytotoxic activity. Three of 5 nude mice transplanted with KB/IL-2 cells were completely cured of their tumor, and all 3 mice survived for over 120 days. All 5 nude mice transplanted with KB/lacZ cells, and all 5 nude mice transplanted with KB cells died within 120 days as a result of tumor progression. In conclusion, transduction of IL-2 gene tumor cells was corroborated by the high level of IL-2 produced by KB/IL-2 cells. The mechanisms of tumor rejection on KB/IL-2 transplanted nude mice were thought to be that effector cells stimulated by IL-2 derived from transplanted KB/IL-2 cells killed tumor cells, and IFN-gamma produced by activated NK cells showed a synergistic effect on tumor cells-killing.

[Thymidylate synthase expression in patients with hypopharyngeal carcinoma].

We analyzed the relationship between clinical response to neo-adjuvant chemotherapy including 5-fluorouracil (5-FU) in patients with hypopharyngeal carcinoma (HPC) and thymidylate synthase (TS) expression in their tumors. TS expression was evaluated with immunohistochemical staining techniques on biopsy specimens from HPC patients. TS immunostaining was divided into four levels (TS0-TS3) according to its level and pattern. The relationship between prognosis, tumor size, nodal status, differentiation of tumor cells and TS expression were also investigated. There was a statistically significant association between the level of TS expression and tumor size (p < 0.01). In terms of the effectiveness of chemotherapy, tumor differentiation, nodal status and prognosis, a statistical difference was not found in TS expression. These results suggest that the level of TS expression may show the degree of tumor proliferation, but may not necessarily be useful to obtain a response to chemotherapy including other drugs, e.g., cisplatin and other derivatives of platinum.