Isao Ono

Tumor angiogenic activity of gynecologic tumor cell lines on the chorioallantoic membrane

Tumor angiogenic activity (TAA) from tumor angiogenesis factor (TAF), produced by 24 cell lines of various kinds of gynecologic tumors, was assayed onto chorioallantoic membranes (CAMs) of chick embryos. Methylcellulose (1%) pellets containing 1 x 10(7) cells were placed on 8-day-old postfertilized CAMs, and the grade of neovascularization was assayed 3 days after inoculation. Neovascularization occurred prominently in such cell lines, as HTBOA (poorly differentiated ovarian carcinoma), HUOCA-II (poorly differentiated clear cell adenocarcinoma), HWUA (poorly differentiated endometrial adenocarcinoma), and in HKUS (uterine cervical small cell carcinoma); however, neovascularization did not occur in SNK (uterine leiomyosarcoma line). The cell lines which secreted TAF showed high heterotransplantability in the nude mice and produced rapidly growing tumors which were rich in blood vessels. However, the SKN line which did not secret TAF was not transplantable. These results suggested that there was a close relationship among TAA, transplantability, and tumor growth rate.

Heterotransplantation of mixed mesodermal tumor cells in nude mouse—Histology of metastatic foci

The mixed mesodermal tumor has an admixture of carcinoma and sarcoma. The HIRS-BM tumor cell line, derived from the mixed mesodermal tumor, was transplanted into the peritoneal cavity of BALB/c nude mice, and the metastatic foci were examined histologically and karyologically. The HIRS-BM cells produced mixed mesodermal tumors (admixture of adenocarcinoma and rhabdomyosarcoma) resembling the original tumor. The normal interstitial tissue was not present on the boundary of the sarcoma and carcinoma. These results support the combination theory as the cause of mixed mesodermal tumor.

Establishment and characterization of a human ovarian anaplastic carcinoma cell line

Ovarian carcinoma cell line HTBOA was established from a human ovarian anaplastic carcinoma. It has been proliferating stably since the beginning of culture 3 years ago after 91 passages. The cells were spindle like, oval, and polygonal in shape, and the nuclear chromatin was coarse in grain with many nucleoli, showing neoplasticity and pleomorphism. The cells proliferated rapidly, and the population doubling time was 24-28 hr. The chromosomes showed a wide distribution of aneuploidy, the mode was in the hypotriploid range, and many marker chromosomes were observed. Heterotransplantation was easy, and subcutaneous transplantation of 1 X 10(5) cells in nude mice forms a tumor that is histologically similar to the original anaplastic carcinoma. The most noteworthy characteristic of the cell line was that it caused granulocytosis in nude mice with carcinomas, and formed the colonies of granulocytes in an in vitro culture system. The cell line was considered to be producing a granulocyte colony-stimulating factor.

N-myc gene amplification and neuron specific enolase production in immature teratomas

The primary tumour tissues from 13 teratomas were investigated, 3 cases of immature teratoma (1 of pure type and 2 of mixed type), 5 cases of dermoid cyst, and 5 cases of mature solid teratoma, with special reference to N-myc gene amplification, productivity of neuron specific enolase (NSE), and the presence of double minutes (DMs). The possible relationship between these variables and malignancy of the tumours was also examined. N-myc gene amplification and NSE production were recognized in the primary tumour tissues and the first and the third passage cultured cells of all of the 3 cases of immature teratoma containing immature neural tissues. In 2 cases DMs were recognized. In dermoid cysts and mature teratoma, neither N-myc gene amplification nor NSE production were recognized in either the primary tumour tissues or cultured cells. The chromosomes were normal. Malignancy of teratoma is generally decided by the clinical stage and histological grade, but a more securely based decision is necessary where an immature teratoma contains immature neural tissues. The presence of N-myc gene amplification, NSE productivity and the presence of DMs may be valuable.

Establishment and characterization of a human thyroid carcinoma cell line (HOTHC) producing colony stimulating factor

A cell line designated HOTHC was established from an anaplastic carcinoma (giant cell type) of the thyroid gland of 80-year-old woman. The HOTHC line grew rapidly in multilayer without contact inhibition, and more than 120 serial passages were made within 27 months. The cells were spindle or polygonal in shape and revealed neoplastic and pleomorphic features. These cells were characterized as containing coloid droplets and poorly developed rough-endoplasmic reticulum in the cytoplasm. Doubling time was about 24 hours and plating efficiency was about 70%. The karyotype exhibits hyperploidy and marker chromosomes, and the modal chromosome number ranged between 77–90. The HOTHC cells were transplanted into the subcutis of BALB/c nude mice and produced anaplatic carcinomas (giant cell type) resembling the original tumor.The HOTHC cells produced colony stimulating factor (CSF) and caused granulocytosis in the mice.