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G-CSF, -: , , , Dr. Ken Alibek

2. ???????? ??????????? ?????????????? ??????????? ??????? ?????? ? ??????? ? ???????? ???????????? ???????????????? ? ????????? ???????? ?????? ?????-??????-??????????? ???????.. ??????? ???????? ???????? ??????? ???????? ????????? ? ??????????????

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G-CSF, -: , , , Dr. Ken Alibek

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    1. 1 ??????????????? ???????????????????? ?????? (G-CSF, ?-???): ???????????? ????????, ?????????????, ???????????? ????????????? ????, ??????????? ????????? ? ??????????? ???????? Dr. Ken Alibek

    2. 2 ???????? ??????????? ?????????????? ??????????? ??????? ?????? ? ??????? ? ???????? ???????????? ???????????????? ? ????????? ???????? ?????? ?????-??????-??????????? ???????.

    3. 3 ????????? ? ?????? ????????? ?????????? — ???? ?? ?????????, ??????????? ???????? ??????? ?????????? (1-? ????? ??????).

    4. 4

    5. 5 ?????????????? ???????? ?????????

    6. 6 ???????? ??????? ??????????? ?????????? ? ??????? ?????????? ??????? «?????????» ?? «????? ????????». ???????????? ????? ??????????? ?????????? ????????? ??????, ??????? ??? ????????????? ??????? ?????? ????????? ? ? ??????? ???????????. ????????? ? ????????? ???????? ?????????? ????? 120 ???? ???????????? (94% ?? ??? ?????????? ??????????). ? ?????????? ???????? (????????, ? ?????? ????????????? ???????????) ????????? ???????????? ?????????? ? 10 ???. ????? ??????????? ???? ???????, ??? ?????- ? ????????????, ???????? ?????????? ??? ???????????????????? ??????; ??????????? ??????????? — ????????? ?????? ???????????. ???????? ? ???????????? ??????????? ?????????? ????? ???????? ????????.

    7. 7 G-CSF: ??????????? ??????????????? ???????????????????? ?????? (Granulocyte Colony-Stimulating Factor, G-CSF) — ???????? ????????? ????????? ???????????.

    8. 8 ???????????????????? ??????? (CSFs): ? ???? ??? ??????????… 1967 ?. ???????? ?????????????? ????????????? ? ??????? ????????, ?? ??????? ??????? ???? ? ?????????????? ????? ???????? ?????. Metcalf D, Foster R. Bone marrow colony-stimulating activity of serum from mice with viral-induced leukemia. J Natl Cancer Inst. 1967 Dec;39(6):1235-45. Metcalf D, Foster R, Pollard M. Colony stimulating activity of serum from germfree normal and leukemic mice. J Cell Physiol. 1967 Aug;70(1):131-2. 1980 ?. ???????? ???????? ????????, ?????????? ???????? «????????????-?????????????? ?????? ??????????????» (GM-DF). Burgess AW, Metcalf D. Characterization of a serum factor stimulating the differentiation of myelomonocytic leukemic cells. Int J Cancer. 1980 Nov 15;26(5):647-54. Metcalf D. Clonal extinction of myelomonocytic leukemic cells by serum from mice injected with endotoxin. Int J Cancer. 1980 Feb 15;25(2):225-33. 1983 ?. ?????? ?????? «G-CSF» ????????????-?????????????? ?????? ?????????????? ???????????? ???????? ?? GM-CSF ? G-CSF. Nicola NA, Metcalf D, Matsumoto M, Johnson GR. Purification of a factor inducing differentiation in murine myelomonocytic leukemia cells. Identification as granulocyte colony-stimulating factor. J Biol Chem. 1983 Jul 25;258(14):9017-23.

    9. 9 G-CSF. ??????? 1985 ?. ?????? ??????? G-CSF ?? ????????????. G-CSF ??????? ???????? ?? ???????? ? ?????????? ????????? ?????, ????????????? ???? ?????? ?????????????. Nicola N.A., Begley C.G., Melcalf D. Identification of the human analogue of a regulator that induces differentiation in murine leukaemic cells. // Nature. 1985, V. 314. P. 625. Welte K., Platzer E., Lu L., Gabrilove J., Levi E., Mertelsmann R., Moore AS. Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factor // Proc. Natl. Acad. Sci. U.S.A 1985. V. 82. P. 1526. 1986-1987 ??. ?????? ??? ??????????????? G-CSF ????????? ????? ?????? ?????????? ???? ?? ????? ??????????? ??? ????????????? G-CSF. Nagata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H, et al. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 1986;319:415-8. Souza L.M., Boone T.C., Gabrilme J., Lai P.H., Zsebo K.M., Murdock D.C., Chazin V.R., Bruszewski J., Lu H. et al. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells // Science. 1986. V. 232. P. 61.

    10. 10 G-CSF ????????????? ??????? ????????: ???????????? ???????? ???????? ?????; ??????????????? ????????; ???????????; ?????????????; ?????????????; ???????????.

    11. 11 G-CSF ????????? ?????? ?? ?? ??????, ? ??????? ??????????????? ??????????????? ???????? ??????????????? (????????????) ??????

    12. 12

    13. 13 ??????????? G-CSF ?? ??????-«??????» ???????????? ?????? ??????? ??????????

    14. 14 ????????????? ??????? G-CSF

    15. 15 ?????????? ???? Jak / Stat, ???????????? G-CSF (1)

    16. 16 ?????????? ???? Jak / Stat, ???????????? G-CSF (2) JAK, ? ???? ???????, ?????????? ????? STAT ??? ???????? ?????????? ?? ???????????? ????????????? ???????? (????????, G-CSF) ????? ??????????????? ????????? ??????????????? ? ?????????? ?????-«???????» ? ????.

    17. 17

    18. 18 ???????????? — ?????????? ??????????? ?????????????? ?????????? ?? ???????????? ????????????? ???????

    19. 19 ?????? «????????» ????????????

    20. 20 G-CSF — ???????????? ???????? G-CSF: ?????????? ????? — 4% ???????????????? ?? ?????? ?????? ???? ? ???????? ??????? ???????????? ???????? ???: 60% — ???????? ?????? 40% — ?????????? ????? ???????????????? ?????? ?????? ????

    21. 21 ? ??????????? ???????? ??????????? ?????????????? G-CSF

    22. 22 Bönig H, Silbermann S, Weller S, Kirschke R, Körholz D, Janssen G, Göbel U, Nürnberger W. Glycosylated vs non-glycosylated granulocyte colony-stimulating factor (G-CSF) — results of a prospective randomised monocentre study. Bone Marrow Transplant. 2001 Höglund M. Glycosylated and non-glycosylated recombinant human granulocyte colony-stimulating factor (rhG-CSF) — what is the difference? Med Oncol. 1998 Dec;15(4):229-33. Review.

    23. 23 Neupogen ????????????? — Amgen, ???. ????????? ? ?????????? ???????? ??????????? ???????? ? ????????? ? ????????????? ?????????????????, ??????????? ???????????????????? ?????????, ??? ?????? ??????? ??????????? ?????? ?????? ??????? ??????????? ? ??????????. ?????????? ??????? ?????????????? ??????????? ? ???????????? ????????? ? ???? ?????? ???????????? ? ???????? ????????? ? ?????? ?????????? ?????????. ?????????? ????????????????? ??????????? ? ??????????????? ? ??? ??????????? ???????????, ????? ??? ?????????? ???????????, ? ????????? ? ????????????? ?????????????????, ??????? ????????? ?????? ????????? ?????????? ???????? ????? ? ??????????? ??? ???????????????. ??????????? ????????????????? ??????-???????????????? ? ?????????????? ????? ??? ????? ????? ???????????. ???????????? ?????????? ? ????? ???????? ??????????? ??????????? (????????, ??? ?????????, ?????????, ????? ??????? ???????) ? ???????????????? ????????? ? ??????????, ?????????????? ? ??????????? ?????????????.

    24. 24 ???????????? ??????????????? ???????????????????? ?????? (G-CSF) ???????????? ? ??????? ?????????????? ?????????? Neupogen® ???????? 175 ??????????? ? ????? ???????????? ??? 18 800 ???????. Neupogen® ??????? ?? ???????? E. coli, ? ??????? ??????? ??? ????????????? ????????????????????? ???????. Neupogen

    25. 25 Neupogen® ???????? ???????? ????????? ??????????? ???????? Amgen Inc. ?????????? — ?????????? ???????? ??????????????? ????????????? ???????????????? ????????????????????? ??????? (r-metHuG-CSF). ????? ????? ?????????????? ??????????????????, ?????????? ????????? (?????????? ????? ?????????????? ???), ? ??????????? N-????????? ?????????, ???????????? ??? ?????????? ? E. coli. ????????? Neupogen® ???????? ?? E. coli‚ ?? ??????? ?? ?????????????? ? ???? ?????????? ?? G-CSF, ??????????? ?? ?????? ????????. Neupogen

    26. 26 Neupogen® ???????????? ????? ?????????? ?????????? ?????????? ???????? ??? ???????????? ??? ??????????????? ????????; ???????? ?????????? ? ???????? ??????????? 1,0 ± 0,6 x 108 ??/?? ????? ???????: ??????? ???????????? ?????????? ? ?????????????? ?????? Neupogen

    27. 27 Neupogen

    28. 28 Neulasta ????????????? — Amgen, ???. ????????? ? ??????????: ???????? ??????????? ???????? ? ????????? ? ????????????? ?????????????????, ??????????? ???????????????????? ?????????, ??? ??????? ??????????? ?????? ?????? ?????????? ???????????.

    29. 29 Neulasta (?????????????? ??????????) ???????? ??????????? ?????????? ??????????????? ????????????? ?et-G-CSF (??????????) ? ???????????-???. ??? ????????? ???-??????????? ???????? ???????????-??? ? ???????????? ????? 20 kD ?????????? ??????????? ? N-???????? ???????? ????????? ???????????. ??????? ???????????? ??? ???-??????????? ?????????? ~39 kD. Neulasta

    30. 30 Neulasta ???????????? ????? ?????????? ?????????? ?????????? ??????? ??? ???????????? (pH 4,0). Neulasta ??????????? ? ????? ?????????????? ??????? ??????? 0,6 ?? ??? ?????????? ????????. ?????? ????? ????????: 6 ?? ???-??????????? (? ????????? ?? ????? ?????); 0,35 ?? ???????; 30,0 ?? ?????????; 0,02 ?? ??????????? 20; 0,02 ?? Na+; ???? ??? ???????? (USP). Neulasta

    31. 31 Granocyte ????????????? — Chugai Pharmaceutical Co. Ltd., Tokyo, Japan / Mayne Pharma Pty Ltd, Australia. ????????? ? ?????????? ???????? ??????????? ???????? ? ????????? ? ????????????? ?????????????????, ??????????? ???????????????????? ????????? ? ??????????? ?????????????? ??? ?????????? ?????????????? ???????? ????? ???? ??????? ???????????????? ???????????. ??????????? ?????????????? ??????-???????????????? ? ??????? ?????? GRANOCYTE ??? ????? ????????????????? ???????????? ??? ????????? ?????????????? ????????? ????? ??????? ???? ?????? ? ????????? ? ????????????? ?????????????????. ????????? ??????????? ??????-???????????????? ????? ?? ?????????. ??????????? ?????????????? ??????-???????????????? ? ???????? ???????. ??????? ??????? ?????????? ???????????.

    32. 32 Granocyte ???????? ??????????? — ????????????? ????????????, ????????????? ????????????? ???????????????? ????????????????????? ??????? (G-CSF). ??????????? ???????? ?? ?????? ????????????? (???). ??????????? ????? ???????????? ??? ~ 20 kD ? ??????? ?? 174 ??????????? ? ?????????????? 4% ????????. ?????? ?????????????? ?????????????????? ???????????? ??????????, ??? ?? ????????? ?????????? G-CSF. Granocyte

    33. 33 ????? ??????? — ????????????????? ??????? ?? ??????? ???????????? ??????????. GRANOCYTE 34 ???????? 263 µg (33,6 ??? ??) ???????????? ? 1 ??. GRANOCYTE 13 ???????? 105 µg (13,4 ??? ??) ???????????? ? 1 ??. GRANOCYTE ???????????? ? ???????????? ???????? ????????? (pH 6,5 ); ???????? 2,5% ?????????; 1% ????????; 1% ????????????; 0,1% ?????????; 0,01% ??????????? 20. Granocyte

    34. 34 ????????? ????????????? — «??????», ??????. ????????? ? ?????????? ?????????? ????????????????? ??????????? II–IV ??????? ? ???????? ??????? ?????????? ??????????? ? ??????? ? ??????????????????????? ????????????????? ????? ???????????? ???????????????? ???????????. ??????????? ??????????????? ??????-???????????????? ? ?????????????? ????? ? ????? ??????????? ?? ????????? ? ?????????????? ????? ????????????????? ????????????. ?????????? ????????????????? ??????????? ? ???????????? ????????? ? ??? ?????????? ? ???????, ?????????? ??????????????? ???????????? ? ??????????? ??????????????? ???????? ?????. ??????? ??????? ??????????? ??????????? ? ????? ?????????? ????? ??????????? ? ???????? ??????? ? ????????????????? ???????????? ??????????. ??????? ??????? ??????????? ? ????????? ? ??????????? ??????? ???-???????? (?????????? ????? ??????????? ?????? ??? ????? 1,0 ? 109/?) ??? ???????? ????? ????????????? ????????. ??????????? ??????????????? ??????-???????????????? ? ?????????????? ????? ? ???????? ??????? ? ????? ??????????? ?? ????????? ? ?????????? ??????????????.

    35. 35 ????????????? ??????????????? ???????? (???): ?????????? ????????????? ?????: ??????? ??? ????????????? ? ?????????? ???????? ?????? 1 ?? ???????? ????????: ???????? ????????: ?????????? 150 ??? ??? 300 ???; ??????????????? ????????: ???????? 60000, ?????? ??????, ???????? ???????, ???? 80, ???? ??? ????????. ????????: ?????????? ?????????? ??? ??????-?????? ???????. ????? ???????    1 ?? ????????? ? ????????????? 150 ???/??; 1 ?? ? 1,6 ?? ????????? ? ????????????? 300 ???/?? ?? ???????? ?? ???????????? ??????, ??????????? ?????????????? ??? ??????????????? ???????? ? ?????????? ?????????, ??????? ???????????? ??????????. ?? 1 ??? 5 ???????? ? ????????? ????????? ???????? ?? ?????? ??? ? ??????????? ?? ?????????? ? ????? ?? ???????. ?????????

    36. 36 ?????????? ????????????? — «????????», ???????. ????????? ? ?????????? ?????????? ????????????????? ? ???????? ??????? ????????????? ???????????, ???????????????? ?????????? ????????, ? ???????, ?????????? ???????????? ???????????????? ??????????, ??? ???????????? ??????????????? ????????????. ?????????? ????????????????? ??????????? ? ?? ??????????? ??????????? ? ???????, ?????????? ??????????????? ??????? ? ??????????? ?????????? ???????? ?????. ??????????? ???????????? ?????? — ???????????????? ????????? ?????????????? ????? (?????), ? ??? ????? ????? ????????????????? ???????, ??? ????????? ?????????????? ????????? ????? ???????? ????????? ?????? ????? ?????????????? ??? ????????????. ?????????? ???????, ???????????? ?? ?????????? ?????????? ????????????? ????????????, ??? ???????? ??????? ? ?????????? ????????????????? ???????????? ?????????? ? ????? ? ???????? ? ??????? ??????????, ????????????? ??? ??????????????? ???????????? (?????????? ????? ????????????? ???????????? < 500 ? 1 ??3) ? ???????? ??? ??????????????? ?????????? ? ????????.

    37. 37 ????????????? ??????????????? ????????: Filgrastim ???????? ???????? ????????????? ?????: ?????????? ??? ???????????????, ?????????? ??? ??????????????????? ????????. ?????? ??????????? ????????: ?????????? 0,3 ?? ??? 0,48 ??; ??????????????? ????????: ?????? ??????, ?????????? 80, ???? ??? ????????. ????? ???????: ??????? ??? ???????? ?? ???????? ?? 1,0 ??? 1,6 ??; ?? 1 ??????? ? ????????? ?????. ??????????

    38. 38 Leukine (rhu GM-CSF) (sargramostim) ????????????? — BERLEX, Bayer HealthCare Biopharmaceuticals, USA. ????????? ? ?????????? ????????????? ??? ???????????? ??????? ??????????? ??????? ? ????????? ?????? 65 ??? ??? ???????? ????? ??????? ? ?????? ??????? ??????????? ? ???????? ????? ????????????? ?????????? ????? ???????????? ??????????. ??????????? ????? ?????????????? ???????????? ?????????????? ?????? — ???????????????? ?????. ?????????? ?????????????? ????? ?????????? ? ?????????????? ?????????????? ???????? ?????. ????????? ?????????????? ???????? ????? ??? ???????? ??????????? ??????????????. LEUKINE ??? ??? ??????????? ????? ??? ? 338 000 ?????????????? ????????? ? ???.

    39. 39 LEUKINE® (????????????) — ??? ?????????????? ???????????? ???????-?????????????? ???????????????????? ?????? (rhu GM-CSF), ????????????? ? ??????? ?????????????? ?????????? ? ????????? (S. cerevisiae) ?????????????? ???????. GM-CSF — ??? ??????????????? ?????? ?????, ????????????? ???????????? ? ?????????????? ??????????????? ??????-????????????????. LEUKINE — ??? ????????????, ????????? ?? 127 ???????????, ?????????? ??? ???????? ???????????? ??????????, ? ???????????? ????? ? 19500, 16800 ? 15500 ???????. ?????????????? ?????????????????? LEUKINE ?????????? ?? ?????????? ????????????? GM-CSF ??????? ??????? ? ??????? 23. ?????????? ????????? ????? ????? ?????????? ?? ?????????? ???????. Leukine

    40. 40 ????? ???????: ?????????? ???????????? ??????? ?? ??????? (500 ???/??) ? ??????????? ??????????? (1,1% ??????????? ??????); ?????????? ????? ????????????????? ??????? (250 ???) ??? ????????????, ??????? ?????????? ?????????? ? 1 ?? ?????????? ???? ??? ???????? (USP) ??? 1 ?? ??????????????????? ???? ??? ???????? (USP). ??? ?????????? ? ????????????? ????????. ??????: 1 ?? ???????? LEUKINE ???????? 500 ??? (2,8 x 106 ??/??) ?????????????; 1,9 ??/?? Na+ EDTA; 1,1% ??????????? ??????; ?????? ?????????????????? LEUKINE ???????? 250 ??? (1,4 x 106 ??/??????) ?????????????; ??????? LEUKINE ?? ??????? ? ????????????????? LEUKINE ?? ??????? ????? ???????? 40 ??/?? ????????? (USP); 10 ??/?? ???????? (NF); 1,2 ??/?? ??????????? (USP). ???????? ?????????? LEUKINE — ?????????????? 5,6 x 106 ??/??. Leukine

    41. 41 Leucomax (rhu GM-CSF) ????????????? — Novartis/Schering-Plough, USA/Switzerland. ????????? ? ?????????? ??? ????????????????? ??????? (????????, ????????????) ??? ???????? ??????? ??????????? ?, ?????????????, ???????? ????? ????????, ? ????? ?????????? ?????? ????? ????????????. ??? ???????????? ? ????????? ????????? ???????? ????? ??? ????????? ?????????????? ?????????? ??????? (Leucomax ?? ??????????? ????? ? ????????????? ????????????).

    42. 42 ??????????? ???????? (???) — ????????c??? (Molgramostim) ????? ???????: ???????, ?????????? ????????????????? ??????? ??? ????????. ??? ????????????? ? ?????????? ????????. ??????: 1 ?????? ???????? 300 ??? (3,33 x 106 IU) ?????????????; ????? 50,0 ?? ?????????; 0,28 ?? ????????? ???????? ???????; 2,6 ?? ????????????? ??????? ??????; 0,1 ?? ???; 1,0 ?? ????????????? ?????????. Leucomax

    43. 43

    44. 44 “?n-label” ??????? ???????????? ?????????? ??????????????? G-CSF ?????????, ??????????? ?????????? ? ????????????? ????????? ??????? ???????? ????? ???????????, ????????? ?????- ? ????????????? ?????????????? ??????????????? ????????? ?????? (hematopoietic stem cell transplantation) v ??????? ??????????? ?????????? v ?????????? ? ?????? ??????????? ????????, ??????????? ??? ????????? ???????? ????????

    45. 45 ??????? ??????????? ??? ???? ????????????????? ??????? ????? ?????????????? ??????? ???????? ????????? ???????? ????????. ???????? ?????? — ???????, ?????, ?????????????? (?????- ? ???????????????). ?????? ????????????????? ?????? ????????? ?? 7–12 ???? ????? ???????? ???????????????, ?? ????????? ?? ??? ????????? ??????????? ?????? ????????? ????????? ? ????? ??????? ?????. ???????? ?? ???????????? ?????????????? ????? ? ???? ??????? ????????????? ?????????? ?? 3–6 ??????. ???????????????? ?????????? ????????????????? ???????????? ?????? ??????? ???????????? ??????????? ? 88% ?????????????? ???????. ???????, ???????? ?? ??????? ? ??????? ?????????, ??????????? ???????? ?????????????, ???????, ? ???? ???????, ???????????? ?????????? ?????????: 1) ?????????? ??? ????????????? ? ????????; 2) ??????????? ???? ? ??????? ????; 3) ????????? ????????; 4) ???????? ????????? ????????; 5) ????? ???????????????????? ??????????; 6) ?????? ? ??????????? ????? ???????; 7) ???????? ???????? ? ????????????? ????????????? ??????? ???????? (???????????? ?????????? ? ??????????? ?????????, ????????? ?????? ??? ????? ? ?. ?.).

    46. 46 ??????? ??????????? ??? ???? (2) ??????? ???????, ??? ??? ?????? ? ?????????? ???????????? ?????????? ?????????? ? ?????????????? ????? ?????? ?????????? ?? ????? 4000 ? 1 ???, ? ??????????? — 120 ? 109 ??/?. ????????? ???????? ???????? ???? ????????? ??????????, ?? ????? ?????? ???? ?? ????? 1500–2000 ? 1 ???. ???????? ????????????? ???, ????????????? 4 ??????? ????????? ?????- ? ?????????????. ??? ??????? ??????? ???????????????? ????????????? ???? ???????? ???????????? ??????????. ??? ?????????? ???????????? 0,1 ? 109 ??/? ?????? ????????? ???????? ?????????? ? ????????. ??? ????????? ?????????? ??????? ????????? ?????????? ???????????: ??? ?????????? ????? ??????????? ? ???????????? ???????? ????? 1000 ? 1 ??? ??? ?????????? ? ?????????? ??????????? ???? ???? 38,3°? ?????????? ??? 38°? ????????? ? ?????????? ? 1 ???. ???? ??????????? ?????? ????? ???? ??????, ????????????? ??????????? ??????? ??????????. ??????????? ??????? ????????? ???????? ???????????????? ???????? ? ????????????????? ???????????.

    47. 47 G-CSF ? ????????? ? ????????? ????? ??? ?????????? ? ????????? ??????????????????? 4 ?????????: Filgrastim (Neupogen) Amgen 5 ???/??/???? Lenograstim (Granocyte) Chugaï 150 ???/?²/???? Pegfilgrastim (Neulasta) Amgen 6 ?? Sargramostim GM-CSF (Leukine) Bayer 250 ??/?²/????

    48. 48 ?????????? G-CSF ? ????????? ?SCO ???????????? (2006) 1. ???????? ???????????? ??????????? ? ??????? ????????????? ???????????? ??????????: — ????? ????????????; — ????? ????????????, ?????????? ???????????? ? ?????????????; — ????? ?????????????? ???????? ?????. 2. ?????????? ????????????? ?????????? ???????????? ??? ?????????? ??????? ????? ???????. 3. ?????????? ??????????? ??? ?????????????? ???????? ????? (?????????? ??? ????????????). 4. ??????????? ??????? ??? ?????????????? ??????-????????????????. 5. ??????? ?????? ???????? ? ????????????????????? ????????. 6. ??????? ?????????? ????????. 7. ????????? ? ????????? ????????????.

    49. 49 ??????????????????? ???????????. ????????? ???????????? ?SCO ???????????? ?????????? ????????????????????? ??????? ???????? ?????????, ?????????? ??????? ?? ???????????????????? ??????, ??????? ???????? ????? 40% ?????????? ???????????, ??? ??? ???????????? ???????????????, ????? ???: — ??? ??????? ????? ???????????, — ??????????? ????? ????????????; — ??? ??????????? ????????????, — ??????? ????? ?????????, ????????? ??; — ?????????? ????????? ????????? ???????; — ???????????? ??????????.

    50. 50 ??????????????????? ???????????. ????????? ???????????? ASCO ???????????? ????????????? CSFs ????? ??????? ??????????? ?????????? ??????????? ? ???? ??????????? ?????? ????????????. ? ????????? ?????? ??????????? ??????, ?????????????????, ??? ????????????? CSFs ??????????? ????????? ? ????? ???????????? ?????????????? ?????????.

    51. 51 ?????????? G-CSF ??? ?????????? ????????????? ???????????? ?????? ???????????? ????????, ??? ?????????? G-CSF ????????? ??????????? ????????? ????????????? ??? ????????????. ??? ???? ????????, ??? ??????? ??????? ??????? ??????? ?? ?????? ??????????? ???????. ?? ????????, ???, ????? ???????????????????? ???????????, ?????????? ???? (?? ????????? ?? ???????????? ???????????) ???????? ???????????? ? ???????? ????? ????????, ?????????? ?????? ????????.

    52. 52 ?????????? G-CSF ??? ?????????? ???????? ????? ??????? ???????????? ????????????, ???, ??? ???? ????? ????????? ?????????? ?????, ????? ?????????? ????????? ??????? ?????? ????????????, ? ?? ???? ??????????. ????????. ??? ???????? ?????? (Citron et al JCO 2003) ???????? ?????????? ?????????????, ???????????? ? ?????????????? ?????? 2 ?????? vs. ?????? 3 ?????? ???????? ???????? ????? ???????? ?? 3 ???? ?? 26% (p = 0,010) ? ????? ?????? ?? 31% (p = 0,014).

    53. 53

    54. 54

    55. 55

    56. 56 ?? ?????? ????????????, ??????????? ?? ????????, G-CSF ?????? ????????????? ???? ? ???????????? ? ??????? ???????? ? ???????????? ???????????, ????? ???: ?????????? ???????; ????????? ??????? ????????; ?????????????? ??????????? ????????? (inflammatory bowel disease); ?????? 1-?? ????; ??????? “????????????? ?????? ???????” (??? ????????? ??????). ????????????? ??????? ?????????? — ???????????? ??????? ????????. ???????? ? ???????????? ???????????

    57. 57

    58. 58 ?????????? G-CSF ??????????? ??? ????????? ????????????? ????????? ?????? ? ????? ??????? ?????????????? ??????????? ????? ??????????? ??????? ? ?????????????? ?????? ????????????? ????????. ??? ?????????????? ??????????: 1) ??????????????? ???????? ????????? (????-, ??????????) ??????; 2) ?????????? ?????????? ??????????? ????????????? ????????? ?????? ????? ?? ??????????? ?? ???????? ????? ? ??????? G-CSF. 7 ?? ?? ?????? ??????? (I–IV), 2004-2007 ??. (????????!) ??????? ????????

    59. 59

    60. 60 ???????????????????? ???????: ?????????????? ???????????, ?? ???? ?? ?????????? ??? ??????? ???????? ?????????? ?? ???? ?? ???????????. ? ???????? ?? ? ?????????? ?????????? G-CSF ????????????? ????????? ?????????? ? ????????????? ? ??????????? ????? (? 2 ??; n = 46, odds ratio 0.21; 95% CI, 0 to 57.52) ? ??????????? ?????????? ?????????? ?????????? (? 3 ??; n = 91, weighted mean difference 27.56; 95% CI, 17.56 to 37.56). ?????????? ????????????????? ?????????????? ?? ?? ????????????? G-CSF ? ???????? ???? ?????? ??? ???????????, ?????????? ??????????????. Sprigg N and Bath PMW. Colony Stimulating Factors (Blood Growth Factors) Are Promising but Unproven for Treating Stroke. Stroke 2007; 38, 1997-8.

    61. 61 ??????????? ? ???-?????????????? ??????????? ???????????? ??????????? ????????, ??? ?????????? ??????????? ??? ??? ??????? ??????? ?????????????? ? ?????????? ?? ????????????? ????????. ????????? ???????? 258 ???-?????????????? ? ????????????? ?????????. DR Kuritzkes. Neutropenia, Neutrophil Dysfunction, and Bacterial Infection in Patients with Human Immunodeficiency Virus Disease: The Role of Granulocyte Colony-Stimulating Factor // Clin Infect Dis. 2000 Feb;30(2):256-60. Kuritzkes DR, Parenti D, Ward DJ, et al. Filgrastim prevents severe neutropenia and reduces infective morbidity in patients with advanced HIV infection: results of a randomized multicenter controlled trial. AIDS 1998; 12:65–74.

    62. 62 ??????????? ? ????????????? ER Gillan, RD Christensen, Y Suen, et al. A Randomized, Placebo-Controlled Trial of Recombinant Human Granulocyte Colony-Stimulating Factor Administration in Newborn Infants With Presumed Sepsis: Significant Induction of Peripheral and Bone Marrow Neutrophilia Blood, Vol 84, No 5 (September I), 1994: pp 1427-1433 42 ????????????? ? ?????????????? ????????????? ???????? ? ?????? ??? ??? ????? ???? ????????? ?? ?????? ??? ????????? ??????? ???? ?????? ??? ??????????????? G-CSF ????????. ?????? ???????????? ?????????????? G-CSF ???????? ?????? ???????????. ??????????? ???????????? ????????? ?????????? ???????????? ??????????? ? ?????????????? ????? ? ??????? ?????. ?????????? ?????????? ??????????? ???????????? ??????????? ????????????? ??????????????? G-CSF ??? ??????? ????????????? ??????? ? ??????????? ? ?????????????.

    63. 63 ????????????? ??????? ?????????? ??????????? ? ????????? ??????? ?????????? ???????? ??????? ??????????? ??????????? ??? ??? ???????????? ??????? ???????????? ??????????? (?????????? ???????, ?????? 1-?? ????, ????????? ??????? ????????)

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