Naohisa Oku

Establishment of an oral squamous cell carcinoma cell line(NOS-1) exhibiting amplification of the erbB-1 oncogene and point mutation of p53 tumor suppressor gene: its biological characteristics and animal model of local invasion by orthotopic transplantationof the cell line

We established a new cancer cell line, NOS-1, which was derived from a human oral primary squamous cell carcinoma. Geneticin treatment was adopted to eliminate contaminating fibroblasts and to enrich tumor cells in the early stage of the culture. The NOS-1 cells showed epithelial morphological features with light and electron microscopy, and immunohistochemical analysis confirmed their epithelial origin. Overexpression of mutant p53 protein, a p53 point mutation at codon 248 with transition from CGG to TGG, and amplification of the erbB-1 oncogene/epidermal growth factor receptor gene were also observed in NOS-1 cells. The NOS-1 cells formed tumors in nude mice when transplanted subcutaneously into their backs. Further, they were transplantable orthotopically in the tongues of nude mice, and the transplanted tumors in the tongue showed diffuse invasion without forming capsules. The NOS-1 cells were useful for elucidating the mechanism involving p53 inactivation and erbB-1 oncogene amplification, as well as treatment of oral cancer.

Establishment and characterization of a human adenoid cystic carcinoma line of the salivary gland which is serially transplantable and spontaneously metastasises to the lung in nude mice

Adenoid cystic carcinoma (ACC) is a rare malignant tumour of the head and neck occurring in the salivary glands. We established a human ACC line which is serially transplantable in nude mice and designated it as KOA-1. The KOA-1 tumour doubled in 9.3 days and retained the histological characteristics of a solid pattern of ACC even after 22 serial passages. The KOA-1 metastasised to the lung when transplanted subcutaneously into the back. This tumour line may serve as a useful model for exploration of the biological behaviour and treatment of human ACC.

Comparison of the mode of action of ras p21 with those of protein kinases A and C in the stimulation of gene expression in NIH/3T3 cells

To compare the mode of action of ras p21 with those of protein kinases A and C in the regulation of gene expression in NIH/3T3 cells, we investigated the transcriptional activity of various enhancer/promoters and enhancer motifs in the cells transfected with the c‐Ha‐ras val12 complementary DNA (cDNA). The results indicate that the c‐Ha‐ras val12 protein stimulates the enhancer/promoters of the c‐fos gene, the metallothionein IIA gene, the simian virus 40 (SV40) virus genome and the Rous sarcoma (RS) virus genome, and the serum‐response element and the 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐response element in a manner independent of protein kinases A and C in NIH/3T3 cells.

A clinical study of local recurrence after surgery in patients with squamous cell carcinoma of the oral mucosa.

1990年～1991年の口腔粘膜扁平上皮癌手術症例のうち, 原発巣再発をきたした22例について臨床的に検討し, 以下の結果を得た。1.舌癌22例中原発巣再発は9例に認められた。再発は局所進展例で舌半側切除, 亜全摘, 全摘を施行した症例に多かった。2.下顎歯肉癌の原発巣再発は42例中7例に認められた。再発はT4の局所進展例だけではなくT1・T2で口内法による下顎骨辺縁切除を施行した症例にも生じた。また, X線所見や組織学的悪性度と再発との関連性は認められなかった。3.口底癌の原発巣再発は17例中4例に認められた。再発はT2・T3で下顎骨辺縁切除を施行した症例に生じた。組織学的悪性度と再発との関連性は認められなかった。4.上顎歯肉癌の原発巣再発は22例中2例に認められた。再発はT1～T3の症例にはみられなかった。5.再発例22例のうち予後良好は7例のみで, 5年累積生存率は34.1%であった。