Bielins'ka I V, Lynchak O V, Rybal'chenko T V, Hurniak O M
Fiziol Zh (1994). 2014;60(4):40-9.
The effect of the protein kinase inhibitor maleimide derivative (MI-, 1, 1-(4-Cl-benzyl)-3-CI-4-(CF3-phenylamino)- 1H-pyrrole-2,5-dione) on blood cells of rats with 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis has been studied. Administration of MI-I1 at 2.7 mg/kg for 20 weeks on DMH-induced carcinogenesis prevents anemia, which is a consequence of cancer and complicates it. This is confirmed by a reduction in the numberofreticulocytes (0,19(0,15;0,21)x 10(12)/1)and restoration of mean corpuscular hemoglobin (18,02 (17,44;19,03) pg) and mean corpuscular hemoglobin concentration (309,42 (292,38;318,27) g/L) to a control value (0,17 (0,15;0,19), 18,31 (17,95;18,45), 310,78 (306,25;316,18), respectively) in contrast to the group DMH (0,28 (0,24;0,39); 17,50 (17,00;17,96); 288,10 (284,71;303,73), respectively). MI-I normalizes the number of monocytes (1,40 (0,95;2,50)x 10(9)/L) and platelets (646,32 (575,23;700,50)xl10(9)/L) in the blood after 26 weeks ofexperiment; in the DMH group, the values are significantly higher (1,97 (1,52;2,58), 783,90 (687,64;922,27), respectively) as compared to control group (1,23 (0,94; 1,68), 629,34 (590,19;711,48), respectively). MI- 1 reduces the involvement of these cells in the tumors progression and metastasis. Reduction of the monocytosis and thrombocytosis may be mediated by: 1) a decrease in the number and size of tumors and, consequently, the influence of their cytokines on hematopoietic tissue; 2) suppression of proliferation and differentiation of hematopoietic progenitor cells through inhibiting of receptor protein kinases of vascular endothelial and epidermal growth factors and non-receptor PDKI-, Src- and Syk- kinases, that are involved in hematopoiesis and carcinogenesis.
研究了蛋白激酶抑制剂马来酰亚胺衍生物（MI-1，1,1-(4-氯苄基)-3-氯-4-(三氟苯基氨基)-1H-吡咯-2,5-二酮）对1,2-二甲基肼（DMH）诱导的大鼠结肠癌发生过程中血细胞的影响。以2.7mg/kg的剂量给予MI-1，持续20周，可预防DMH诱导的致癌过程中出现的贫血，贫血是癌症的一个后果且会使病情复杂化。这一点通过网织红细胞数量的减少（0.19(0.15;0.21)×10¹²/L）以及平均红细胞血红蛋白（18.02(17.44;19.03)pg）和平均红细胞血红蛋白浓度（309.42(292.38;318.27)g/L）恢复到对照值（分别为0.17(0.15;0.19)、18.31(17.95;18.45)、310.78(306.25;316.18)）得到证实，与之形成对比的是DMH组（分别为0.28(0.24;0.39)；17.50(17.00;17.96)；288.10(284.71;303.73)）。实验26周后，MI-1使血液中单核细胞数量（1.40(0.95;2.50)×10⁹/L）和血小板数量（646.32(575.23;700.50)×10⁹/L）恢复正常；在DMH组中，这些数值与对照组（分别为1.23(0.94;1.68)、629.34(590.19;711,48)）相比显著更高（分别为1.97(1.52;2.58)、783.90(687.64;922.27)）。MI-1减少了这些细胞参与肿瘤进展和转移。单核细胞增多症和血小板增多症的减轻可能是由以下原因介导的：1）肿瘤数量和大小的减少，以及因此其细胞因子对造血组织的影响；2）通过抑制参与造血和致癌过程的血管内皮生长因子、表皮生长因子的受体蛋白激酶以及非受体PDK1-、Src-和Syk-激酶，抑制造血祖细胞的增殖和分化。
