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Interaction of interleukin-11 with cytotoxic therapies in vitro against CEM cells and in vivo against EMT-6 murine mammary carcinoma

✍ Scribed by Beverly A. Teicher; Ying-nan Chen; Gulshan Ara; Yasunori Emi; Yoshihiro Kakeji; Yoshihiko Maehara; Susan Keyes; David Northey


Publisher
John Wiley and Sons
Year
1996
Tongue
French
Weight
687 KB
Volume
67
Category
Article
ISSN
0020-7136

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✦ Synopsis


Interleukin

-I I (rhlL-I I) is a cytokine that has been shown to enhance the recovery of bone marrow and intestinal crypt cells after cytotoxic insult with radiation or anticancer drugs. The current study examined the effects of rhlL-I I on the response of CEM human lymphoblastic leukemia cells and on the EMT-6 murine mammary carcinoma in vivo to cytotoxic anticancer therapies. Exposure of CEM cells to rhlL-l I for 24 hr did not alter the cytotoxicity of melphalan or radiation, increased the cytotoxicity of CDDP (I 00 pM) and 4-hydroperoxycyclophosphamide (50 PM) and decreased the cytotoxicity of 5-fluorouracil and ara-C toward the cells. Treatment of mice bearing the EMT-6 tumor with rhlL-I I twice daily for 4 days prior to and the day of cytotoxic therapy resulted in no significant change in the tumor cell killing or bone marrow CFU-GM killing by melphalan, cyclophosphamide, thiotepa, CDDP, radiation, 5-fluorouracil or ara-C. Administration of rhlL-I I twice per day on days 7-I 8 to EMT-6 tumor bearing animals receiving high dose chemotherapy (melphalan, thiotepa or cyclophosphamide) as a single dose on day 7 followed by mobilized peripheral blood cells on day 8 and rhG-CSF on days 8-20. tended to prolong the tumor growth delay produced by the drugs. This rhll-l I treatment also resulted in a more rapid recovery of white blood cells and granulocytes in the animals. Furthermore, animals treated with rhlL-I I had improved survival rates compared with animals receiving all other normal tissue support without rhlL-I I.