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C Arai

Publications and source records attributed to C Arai.

58 records · Page 4Linked to original sources

Establishment of an in vivo human myeloid leukemia model in the SCID mouse.

We succeeded in establishing a human myelogenous leukemia model in severe combined immunodeficient (SCID) mice by transplanting 2 x 10(7) ML-2 cells intraperitoneally (i.p.) with cyclophosphamide (CTX) pretreatment. Two months after transplantation, 9 of 10 mice developed leukemia and leukemia cells were detected in the peripheral blood (PB) and bone marrow (BM). The main findings at autopsy were peritoneal and pleural effusions and large tumor masses involving the peritoneal organs. However, successful transplantation required injection of a large number of cells. We therefore established a new cell line, ML-2S, from the PB of a mouse with ML-2 leukemia. Although only 2 x 10(6) ML-2S cells were inoculated, ML-2S induced the same pattern of leukemic dissemination reminiscent of the parent ML-2 cells. Compared to ML-2, progression of ML-2S was slow, suggesting that ML-2S is suitable as a leukemia model to study treatment. Furthermore, we confirmed that ML-2S cells are of human origin using isoenzyme analysis and also that ML-2S and ML-2 cells have the same phenotypic character by cell surface marker analysis.

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In vivo therapeutic effects of IFN-gamma on human myelogenous leukemia in a severe combined immunodeficiency mouse model.

BACKGROUND: Results of clinical trials of IFN-gamma on the treatment of various types of leukemia are not so promising, regardless of the antiproliferative activity against leukemic cells and expected immunomodulatory effects. In this study, we have re-evaluated the anti-leukemic effects of natural human IFN-gamma (nHuIFN-gamma) using an established human myelogenous leukemia model in SCID mice. MATERIALS AND METHODS: SCID mice transplanted with human myelogenous leukemia cell line ML-2S received subcutaneously 5 x 10(4) IU/mouse of nHuIFN-gamma at 5 times/week for 5 weeks. RESULT: nHuIFN-gamma significantly prolonged the lifespan of SCID mice in leukemic crisis. Percentages of ML-2S cells in the peripheral blood were also significantly decreased by the IFN-gamma treatment. Histopathological examination revealed that IFN-gamma treatment suppressed the replacement of pancreatic cells by tumor cells and the formation of tumor masses in the intestine. CONCLUSIONS: These results suggest that IFN-gamma is effective against human myeloid leukemia, especially extramedullary tumor mass-forming type in the peritoneal organs. Our results further suggest that studies employing SCID mice leukemia model would help in devising appropriate therapeutic strategies of IFN-gamma based on the specific characteristics of each leukemia subtype.

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