I ?????????????? ??????????????? ??????-???????????? ??????????? (2006 ???)

1
????????? ???? ? ???????
????????? ??????? ??????????? ????????????
??????????? ??????, ?.?.?.?.?.??????????????
2
????????
????????????? 3 ?. 28.09.2008
????????? ????, ??????? 3 ?. 29.09.2008
???????????? ??????????? ?????? 3 ?. 29.09.2008
???????????? 3 ?. 30.09.2008.
???????????????????? ??????????? 3 ?. 30.09.2008.
???????????????????? ??????????? 3 ?. 30.09.2008.
3
I ?????????????? ???????????????
??????-???????????? ??????????? (2006 ???)
4
?????????????

• ????????????? (??????? ??????????)  ???????,
  ????????????? ? ????? ????????? ???????????????,
  ? ?????????? ??????? ?????????? ?????? ??????
  ?????
• ???????????? ????? ???? ?? ??????????
  ??????????????? ?????? ?????????.
• ??? ?????????? ??????? ?????? ????? ??????????
  ????? ????????.

5
?????????? ??????? ??????
6
???????? ?????????? ?????? ??????

• ???????????? ?????? ????? ????????? ? ??????????
  ?????????? ????????? ???????? ?????, ?????????,
  ????????(?????????? ? ?????????)
• ? ????? ?? ????????????? ?????? ?????? ?????????
  ????????? ????????, ??????????? ?????????????
  ???? ?????????????? ??????
• ??????? ???????? ???????? ????????? ??? ??????
  ????? ?????? ??????
• ????????????? ?????????? ?????? ????????????
  ????? ???????????????? ?????????

7
?????? ? ?????????

• ???????????????? ? ?????????????????? -
  ???????? ????????? ??????????????? ????????
  ???????
• ? ???? ????????? ????????? ??? ???? ?????????
  ?????? ? ?????????
• ???????????????? ????????
• ???????? ????????? ??????
• ??????? ? ????????? ?????? ??????????? ??????? ?
  ????????? ????????? ??????????????? ???????????

8
????????? ???????? ?????

• ????????? ???????? ????? ?????? ???????????
  ????????? ????, ?????? ??? ???????????? ????????
  ??? ????? ????????? ????????? ???? ???
  ???????????? ???????? ??????? ??????.
• ??????????? ?????????? ???????? ????? ????????
  ???????????? ??????????????? (receptor
  protein-tyrosin kinases)
• P?????????? ????????????? ???????? ???????????
  ????????? ????????, ????????????? ?????????
  G-?????, ??????? ????? ?????????? ???????????
  ???????? (???????????????, ??????????? ?,
  ????????????? ? ? ??.)

9
????????? ???????????

• ??????????? ?????????????????? ( cAMP)
• ????????????? ?
• ??????????? ?????????????????? (cGMP)
• ?????????????? ( DA) ??????????? ? ??????????????
  ?
• ????????????????? (IP3) ??????????? ? ???????
  ?????????? ???????
• ??????? (Ca) ???????? ????????? ?????????????
  

Ca2 response in stably transfected (VR1
receptor) NIH 3T3 cells after stimulation with an
agonist
10
??????? ???????? ?????????? ??????? ? ???????

• ??????????? ????????
• ??????????? ???????? ?????? ???????????
  ?????????? ???????? ? ?????????? ???????? ??????.
  ?????????? ???????? ?? ????????? ? ????????.
• ??????????? ???????? ?????? ???????? ?? ????
  ??????????? ??????
• ???????????? ???????? (????????????? ?????? ?????
  ???? ? ????? ??? ? ????????? ??? ????????? ???
  ??????????, ?????? ?????????? ????? ????????????
  ??????????? ????????)

11
????????? ??????

• ?????? 1 ????????? ??????????? ??????????
• ???????? ??, ??, ??????? ????????
• ?????????? ???????, ????????
• ?????????, ???????? ?????????? ??????? ?
  ????????? ? ? ?
• ?????? 2 ????????? ???????????? ??????????
• ?????????, ??????????? ? G-???????
• ????????? ??? ?????? ??????. Pro BNP ????????
  ????????????????? ?????? ????? Na
• ?????????, ??????? ???????? ??????
• ????????? ? ??????????? ???????????
• ????????? ????????? ????? ????????????????
  ???????????.

12
Fabio Candotti, Luigi Notarangelo, 2002
?????????? ?????????? ??????? ? ? ? ??????????
13
Fluorescence Distribution NF-kB Translocation
Assay
14
?????????? ? bcr/abl-?????????????? ?????????
????????? ? ??????????
15
??????????????? ?????????? ????

• ????? ????????? ras-???? , ? ??????? ??????????
  ??? ?? ??????? ???? ??? ????, ??????????????
  ??????????? ???????? ????? .
• ???? ?? ??? - ?????????????????????? ????,
  ?????????? ? ????????? ????????????? ?
• ?????? - ??????????????????-3-???????? ????
  (PI3K) - ?????????? ??????? ???????? ? ????????
  ????????? ????????????, ?????? ????????
  ??????????????? ?????, ????????? ??????? ????????
  ??? ?? ?????? ????

16
???????? ???????? ?????

• ????????? ????? ???????? ?????? ???????? ???????,
  ???????????? ?????? ??? ? ?????? ( Goustin A.S.
  ea,1986 ).
• ??????? ???? ??????????, ??? ?????? ???????????
  ?? ?????? ???? ??????????? ??????? ????, ???
  ?????????????? ???????. ???, ????????? ????? ????
  ?????? ? ??????????? ?? ???? ??????- ????????????
  ????? ???????????? ??????????????? ? ?????????
  ???????????? .
• ????? ????, ? ??? ??????? ????????????
  ???????????, ???????????? ??????????? ?????? ,
  ????????, ?? ?? ??????????? ???????? ?? ???????
  ?????? ( Stoker M. and Gherardi E., 1987 ).
• ??????? ??????? ???????? ????? ?? ????????
  ???????? - ??????????? ???????? ???????? ???
  ??????????? ???????? ???????? ( ???????????
  ???????? ???????? ??? ???????? Deuel T.F., 1987
  ).
• ???????? ??????? ????????????? ??????? ??????
  ?????

17
? ? ? ? ? ? ? ? ? ? ? ?

• ???????? ???????
• ?????????
• ???????????? ????,
• ???? G 1
• ???? G 0
• ???? S
• ???? G 2
• ??????, ????????????? ??????????
• ???????
• ?????????? ?????????
• ????? p 53
• ??????????????
• ???????
• ????????

18
????????, ??????? ? ????????

• ??????, ??? ???????? ????????, ?????? ??????
  ?????? ??? ? 1663 ????. ?? ??? ??????????????
  ?? ???? ???? ?????? 30-??????? ??????????,
  ??????? ?? ??? ?????? ? ????????? ?????? ??????
  ???? ????? ??????? ?? ????, ??????? ?? ??????
  ????????.
• ?????? ????????? ?????????? ??? ? 300 ???
   ? ????????? ????? ?????? ?????, ?????????????
  ? ????????, ????????? ?? ?????????? ?????????.
  ?? ?????? ??? ?????? ????????? ? ?? ???, ???
  ??????? ??????. ? ?????? ???????? XIX ???? ?.
  ??????? ? ?. ?????, ??????? ??????????? ? ????
  ??????? ??????, ??????? ????????? ??????,
  ?????????, ??? ??????  ??? ???????????
  ? ?????????????? ?????? ???? ????? ??????????.

19
???????????? ????

• ???????????? ???? - ???????????? ????????????????
  ? ??????????????? ????????? ? ?????? ??????????
  ?????? ? ???????, ? ????? ?? ?????????? ??????
  ???????.
• ????? ???? "?????" - ????

20
????????? ???? ??????
??????? ??????

• ?????????

• ???????

• ????????

????????
???????
21
(No Transcript)
22
???????????? ????

• ???????????? ???? ???? ? ??? ???? ???????,
  ??????? ?????? ?????? 30-60 ????? ? ???????????
  ???????? ?????? ?? ??? ????????.

23
(No Transcript)
24
G 0

• ????????? ?? ????? G1
• ?????? ????????????? ?????, ??????? ????????????
  ?? ??? ?????????? ???????
• ????, ?????????? ?????? ?????????? ???????
  ?????????
• ????, ?????????? ?????, ??????????? ??? ?????????
  ??????????????? ????????
• ?????????????, ??????? ????????? ????????? ? ????
  G 0 ? ???? ??????? ? ??? ?? ?????????????? (???
  ???? ??????? ????????? ????????)
• ??????????? ???????? ?????? ????? ? ?????????
  ????????, ??? ???????? ?????????? ??????? ??????
• ??????????? ??? ?????? ?????? ???????? ????????
  ??? ????????????, ? ????? ?????????????. ???
  ?????? ???????????? ???????? ???????????? ?
  ???????? ?????? ?????????.

25
????? ?????????? ?????? ?????????? ?????????

• ????, ?????????? ???????????? ???????????, ????
  ?????? ???????? ??????, ??? ??? ????? ?????????
  ??????.
• ????? ??????? ???????? ??????????
  ?????-???????????? ????????-????????????
  ????????, ????????? ? ?????????? ?????????
  ????????????? (?????????, ?????????, ????????)

26
?????????

• ?????????-????????????? ????????? ??????,
  ??????????? ??????? ?? ????????????? ???????? ?
  ???????????.
• ???????? ????, ????????????????, ??????????
  ??????, ???????, ??????????? ????? ? ????????
  ?????? ? ???? ??????????
• ???????????? ????????? ???????????? ?? a (16
  ??????????????) ? ß (8 ?????????????? )
  ??????????
• ?????????, ??????????? ???????????? ????????,
  ?????????? ICAM ????????????? ??????????
  ???????
• ????????? ??????????? ?????????? ?????? ?
  ???????????? ????????? ?????????????,
  ??????????, ?????????.

27
??????????? ????????
?????????????? ??????
ICAM-1
?????
LFA-1
VCAM-1
???????????? ???????
VLA-4
???
CD44
???????????
c-kit
CXCR4
ICAM - intracellular adhesion molecule VCAM
vascular cell adhesion molecule LFA lymphocyte
function associated molecule VLA very late
antigen SDF stromal cells derived factor
SCF
SDF
?????? ??????
??????????
??????? ????
28
??????
?????????????? ??????
??????? ????
??????? ?????? SDF-1/CXCR4 VLA-4/VCAM-1 CD44/????
.?-??
???
CXCR4
SDF
?????
??????????? ??????
???????????
?????????
29
Figure 1. G-CSF HSC mobilization. a There are
adhesive interactions between HSC and matrix
components in the BM. HSC express a wide range of
cell adhesion molecules (CAM) including CXCR4,
VLA-4, c-kit, CD62L, and CD44. The BM stroma
expresses cognate ligands for these CAMs such as
SDF-1, VCAM-1, KL, PSGL, and HA. b HSC
mobilization results from cytokine-induced
functional changes in the adhesion profile
expressed by the HSC in their relation to the BM
stromal cells, osteoblasts, and other matrix
components. G-CSF induces, through an unknown
cell, the release of a number of proteases into
the BM, including NE, CG, and MMP9. IL-8 and Groâ
release the same enzymes via neutrophils and
monocytes. These proteases cleave several
adhesion molecules thought to play an important
role in HSC trafficking and mobilization,
including c-kit, VCAM-1, CXCR4, and SDF-1. Recent
data suggest that G-CSF treatment potently
inhibits osteoblast SDF-1 expression at the mRNA
level furthermore osteoblasts are the major
source of SDF-1 in the BM. The resultant decrease
in osteoblast SDF-1 may also contribute to
enhanced HSC mobilization especially in response
to G-CSF. Cathepsin G (CG), chemokine receptor-4
(CXCR4), hematopoieic stem cell (HSC), hyaluronic
acid (HA), interleukin 8 (IL-8), kit ligand (KL),
matrix metalloproteinase-9 (MMP-9), neutrophil
elastase (NE), stromal cellderived factor-1
(SDF-1), vascular cell adhesion molecule-1
(VCAM-1), very late antigen-4 (VLA-4), P-selectin
glycoprotein ligand-1 (PSGL).
B. Nervi et al. Journal of Cellular Biochemistry
99690705 (2006)
30
(No Transcript)
31
???????? ????????????? ??????? ??

• CD 62 E (E-????????)
• CD 62 P (?-????????)
• CD 106 (VCAM-1)
• CD 31 (PECAM-1)
• VEGFR-2 (KDR)
• ?D 105 (endoglin)
• CD 144 (VE-cadherin)
• CD 146 (S-endo-1)
• ?D 54 (ICAM-1)
• CD 34

CD54/CD45- CD146/CD45- CD34/CD45-
????????? ??????????
32
???? ????????

• ??????? ?????? ??????????? MPF
• ? ??????? ????????????? ?????????? ?????????
  ??????????????? ????? (cyclin-dependent kinases
  Cdk). Cdk ????????????? ? 1 ?? 5.
• ? ?????? ?????? ?????? ?? ???? G0 ??? ?????????
  ???????? ????? ?????? ?????????? ???????? ??????
  ?- Cdk. ???? ???????? ????????? ?????? ??????,
  ??????????? ??? ?????????? ???.
• ???????? ?????? ?, ?, ?, ?.

??????? ?????? ???????
D Cdk4, Cdk6 ?????? ????? ????? ??????????? ?? ??????? G1/s
?,? Cdk2 ????????? ??????? ??? ? ?????? ???? S
? Cdk1 ??????? ?? G2 ? M
33
?????? ?

• ?????? ? ???????????? ????????? ?????? ? ?????.
  
• ??????? ?? 2 ??????????
• - ????????? ?????? ( ???????? ? ????????????????
  ????????????? ??????? ? ??????) ?
• - ???????????? ??????????? (??????????), ??????
  ??????? ??????????? ? ?????????? ? ???????
  ?????????? ?????.
• ?????????? ??????? ? ?????????? ?? ?? ????
  ??????????, ??? ? ??????????? ??????, ? ?? ????
  ????????????? ? N-????????? ???????, ???????
  ?????????? ???? ?????????? ??? ??????? ????
  ?????? (???????????? ? ???????????????) ?????
  ???? ??? ?????????? ?????????? ? ??????????.
• ??? ?????????? ?????? ? ????? ????????? ??? ????
  ?????? ??? MPF ????????? ????????????
  ?????????. ?????????? MPF ???????? ? ????????
  ????? ?? ??????.
• MPF ????????? ? ????????? ?????? ??????? ??????
  ????????????? ????????, ??????????
  ??????????????????? ?????????? ? ?????????
  ???????.

34
MPF (?????? ?)
?????????? MPF ???????? ? ???????? ????? ??
??????. MPF ????????? ? ????????? ?????? ???????
?????? ????????????? ????????, ??????????
??????????????????? ?????????? ? ?????????
???????. ?????? ? ??????????, ??? ????????
???????????? ???????? ????? ???????????
35
?????

• ??????????????
• ??????????????, ???????????? ????????, ?
• 10 000 ??? ? ?????????? ? ???????? G2 ????
• ???????????? ??????? ???????? (????? ? ? ?)
• ????????????? ???????? ??????? ? ?????????????
  ???????? ? ????????? ???????? ?????? (? ???????
  ??????????, ?????????? ? ???????? ?????????????,
  ??????????)
• ???????????? ??????????? ???????? ? ???????
  ?????? (??????, ???????), ?????????? ???????
  ???????, ?????? ???????????? ??????? ?? ???
  ???????? (?????, ??????).

36
Cell Cycle Representative Image
Hoechst dye and 3 antibodies enable
identification of Cells in G0, G1/G2, S and M
phase
Anti- Ki-67 yellow Anti- BrdU cyan Anti-Phospho
Histone H3 green Hoechst blue
GO G1 S G2 M
20x objective
37
???- ??????????
?
?
?
?- ?????????? ?????? ?-?????? ? ???????? ?-
????????????? ??????
???????????
38
????? ? 53

• ?????? ?????????? ? ????????????? ?????????????
  ????????? ??? ????????? ??????? ?????????
  ??????. ? ????????? ????? ?????????? ??????
  ?????, ? ??????? ???????? ??????????,
  ???????????? ?????????????????? ? ??????
  ?????????? ??? ?????????????? ????????????
  ?????????? ???????????.

39
??????????? ?????? ???????? ????? ??? ?-???

• ??????? 17p ????? ??????? ???????
• ?????????? ?? ???? ??????? ??? ??????? ? ???????
  12 ??????? ?? ?????? ???????

40
???????? ???? p53 ? ??????????????
?? ???????
N
17p-
41
????????? ? ?????? ? ?????? ????? ?-???

• ??????? 17p
• ?????????? ?? ???? ??????? ??? ??????? ? ???????
  12 ??????? ?? ?????? ???????
• ???????????????? ????????? ???????? ?????
  ???????????
• ??????? ??????? ?????????? ? ?????????? ? FC ?
  CHOP
• ?????????????????? ????? ? ??????????

42

• ????????????? ????, ??? ???????? ????????? ?
  ????????? ????????? ????????????.
• ??????? ???? ????? ???????? ? ????????????????
  ???????????? ? ???????????? ????? ????? ?????????
  (??????????? ????????????, ???????? ???????,
  ????????????)

??????? ????? ????
C-raf ??? ???????, ??????? ??????
C-kit ??? ???????
myc ????????????? ??? ???????, ??? ??????? ?????, ???????
N-myc ?????????????
R-ras ??? ??????? ?????
erbA ???????. ?????????????? ??? ???????
Bcr-abl ??????????? ???????????
ras ??? ??????? ?????, ????????????? ??????, ???????? ??????,???????
43
????
?????? D1

•      ?-????????? ???????, ?????????????????
  ????????????? ??? ????????????? ?????? 11q13,
  ??????????? ? ??????????????? ???????? ?????
  ??????? D1
• ?????? D1, ? ????????? ? ????????????????
  ???????? 4 ? 6 (???4/6) ???????? ???????????
  ???????? ?????? ?? G1 ? S-???? ?????????? ?????.
• ? ?????? ???????? D1 ?????? 3 ????? D1 D2 D3, ?
  ?????????? ? ????? ???????????????? D3. (D1
  ???????????????? ?????? ? ????????????? ?
  ?????????????? ???????. )
• ? ????????? ?????????? ?????? ??????????
  ???????????????? ???????????? t(1114)(q13q32),
  ?????????? ? ?????????????? ???????? ?????
  ??????? D1 ? ????????? ???????? ?????????
  ?????????? ?????. ? ?????? ?????????? ??? ??????
  ??????????? ????????? ?????? D1
• - ????????? Cip/Kip ???????????? ??????? ?21, ?27
  ? ?57
• - ????????? INK4 ???????????? ??????? ?15 ? ?16,
  ?18 ? ?19.
• ??? ???? ???????????? ????????? ??????
  D-????????? ??????. ????????? ????????????????
  ????????? ??? ?????????? ??????? ?? ??????
  ????????? ???? ??????? ? ????????? ?????? ????
  ?????.

44
1-2 ??????? ???????? ??????? 3-5
????????????? ????????? ????????????? ???? 6-8
????????????? ??????? 9-12 ???????.
45
????

• ??????? ?????????? ??????? ?1 ????????
  ??????????????? ????????? ??????? ?? ??????
  ??????. ????????????????, ??. 250

46
????????? ?????????? ????? ? ??????

• ??? ?????????? ?????? ??????????? ?????? ?
  ????????, ???? ????????, ??? ?????? ?????? ?????,
  ???? ????????? ?????? ???????? ????????. ???
  ???????? ?????????????? ?????? ????? PDGF
• ??????? ????? ? ??????? ?????????? ????????? ?
  ???????? ????????????? PDGF, EGF, FGF, NGF,
  EPO, IL-2,IL-3

47
??????? ?????

• ??????? ?????
• ????????? ?????????????? ???????? ????? (PDGF)
  PDGF A, PDGF B, VEGF, PLGF,CSF-1 SCF-??????????
  ??????
• ????????? ???????? ????? ???????????? (FGF) a
  FGF, ßFGF, int-2, K-FGF, FGF-5, GFG-6, KGF,FGF-8,
  FGF-9
• C???????? ????????? ???????, ????????????????
  ?????? ????? IGF-1, ???????????????? ?????? ?????
  IGF-2
• ????????? ????????????? ???????? ????? (EGF)
• ?????? ????? ???????? a
• ????????? ???????? ????? ?????? NGF NGF, BDNF,
  NT-3,4,5,
• ????????? ???????? ????? ??????????? HGF
• ???????????????????? ??????? CSF
• ??????????-???????????????????? ?????? G-CSF,
• ???????-???????????????????? ?????? M-CSF,
• ??????????-???????-???????????????????? ??????
  GM-CSF
• ???????????????? ?????? ?????
• TGFß
• BMP

48
???????? - ??????? ????????.

• ?????? ????????????????? ?? ???????????? ?????
  ???????, ? ????? ?????????? ????????
• ????????????? ????????
• ?????????? ????? ???????
• ????????? ?????????? ?21, ??????????
  ??????????????? ?????
• ?????????? ????????? ??????????????, ???
  ????????????? ??????????? ? ??????????? ???????
  ???????? ????????? ????????? ? ???????? ????????

49
????????

• ????????-??? ???????? ??????? ????????, ???????
  ???????? ????????????? ?????????????????? ??? ?
  ????????????? ? ?????? ???????????.
• ? ????????????????? ? ??????? ?????????
  ?????????? ?????? (????????, ?????????) ?????????
  ??????? ??????????, ????????? ??????????
  ?????????? ??????????????????.
• ?? ??????? ??????????? ??????? ???????
  ??????????????? ????????? ?????? ? ??????????
  ??????? ????? ??????? ?????? ?????????????? ??
  ?????????? ??????

50
??????? ??????????????? ????????? ??????.

• ????????? ????????? ?????????? ??????? ??????????
  ??? ????????? ?????????. ??????????? ??????
  ??????? ?? ???????? ???????????? ? ?????? ??????.
  ???????? ????????? ?????? ??????? ?? ????????
  ?????????????? ? ????????????? ????????? ??????.
• ??????????????? ???????? ?????? ????? ???????? (
  apo-?????? ptosis ???????,??????) ? ???????? ?
  ?????????? ???????? ????????? ?????????, ???????
  ????????). ???? ?????? ??????? ???????? ? 1972
  ???? J.F.Kerr ??? ???????? ??????????
  ??????????????? ??????? ?????? ?? ????? ?????????
  ??????.
• ???????? ????????? ?????? ??? ???????? ??????????
  ??? ??????????
• ??????-?????????????? ????? ?????? ?????? ?
  ?????????? ?? ??????? ???????????, ???????
  ????????, ????????????? ??????????? ?????????? ?
  ???????? ??????????????? ????????

51
??????? ??????????????? ????????? ??????.

• ??????? ????? ???????? ????????? ?????? ????
  ??????? ???????????
• ??????????? - ???????? ??????????? ??
  ???????????? ????????? ???????? ? ??????, ???????
  ????? ??????? ??????? ???????? ???????? ?
  ?????????? ? ??? ????????????
• ??????????? - "???????????? ????" ???????
  ????????? ??? ????? ????????? ?? ??????? ????????
  ? ????????? ? ?????????? ?????. ??????? ????????
  ????????????, ???? ?????? ??????, ????????
  ??????????? ? ????????? ??? ??????? ????????????
  ? ??????????.
• ?????????? ??? ?????????? - ???????? ??????????
  ????????????. ???? ? ?????????? ? ??????
  ???????????? ????????? ??????????? ??????
  ??????????, ?? ????? ???????? ?????? ????
  ??????????????? ? ?????????? ??????????? ?
  ??????? ???????? ????????? ? ?????????? ? ???
  ????????????.
• ????????????????? ??????? ??????????? - ? ????
  ?????????? ???? ??? ????????? ????????, ???????
  ?????????? ?????????????, ???????? ???????? ?
  ????????? ???? ? ????? ?? ???????? ?????????
  ?????????

52
????? ????????

• ?????? ?????????????? ?????? ????????
• ??????????? ?????????, ?????????? ????? ?????????
  ????????????? ?? ?????? ??????? ????? 180 ???
  ??????????? (???????? ?? ?????????????), ??????
  ???? ?? ????????? (???????????)
• ?????????? ????
• ??????????? ?????????????? ????????
• ???????????? ?????? ? ???????????? ??????????
  ?????.

CD 95
53
????????? ????????

• 2 ????
• ???????????? ? ?????????? ??????????????? ???????
  ???? ???????? ???????
• ???????? ????????? ???????? ??????????? ????.
  ??????? (??????????? ????????) ?????????? ????? ?
  ?????? ???????????? ????????????? ?????????

54
???????

• ????????? ???????, ??????????? ? ????????
• ?????????? 14 ????? ??????
• ?????????? ????????? (??????? 1,4, 5, 13)
• ????????? ????????? ??????????? ?????? (???????
  2,8,9,10) ICAD
• ??????????? ???????-??????????? ????????
  (??????? 3,6,7)
• ????? ????????? ??????? 9, ????? ??????? 3, ?????
  Bax ?????????????, ???????? ?????????? ?
  ?????????? ????????????? ????????? ?.
• ?????????? ??????? ??????? Bcl-2
• ???????? ??????? ????? Bad, ??????????
  ???????????? ? Bcl-2

55
?????????? ???? ????????

• ??????????? ???, ????????, ???????????
  ???????????, ???????????????, ?????????? ???????
  ???????? ?
• ????????? ??????? 9
• ????????????????? ??????? Fas-R, TNF-R, ?????????
  ??????? 8, Ca 2 (????????? ?? ????????????? C)
• ????????? ???????? ?????????? ??? ?????????
• ????????????? ????? Ca 2 (??????????-???????????
  ???????????????? ???? ??) ,
• ?????????? Zn2 (???????????, ?? ???? ??????????
  ????????????)
• ????????? ??????? ?????????????? ??????

56
????????? ??????? ?????????????? ??????

• ????????? ???????? ?????????? ?????? ??????
  ???????? ??????? ?? ?????????????? ?
  ????????????, ???????? ? ?? ??????
• ?????? ?????????? ????????? ??? ??????????
• ????????? ??????????? ????????????????? ?????????
  ??? ????????????
• ????????????? ???????????? ????????????????

57
????? ????????? ???????? ??? ????????????
?????????????? ???????
??????, ????????????? ????????
??????????? ????????? ?????
???????
? ?????????? ??????? ?????????? ?????????
58
??????????? ?????? 1

• ?-?? ?.66 ??? , ????????? ? ????????? ???????????
  21.05.2007 , ???
• L-8.6610 9/?, ??? 82 ??/?
• ?? 52 ?/?, ??.1.52 6610 9/?
  ???????????????, ???????? ?????? 48.
• ??????, ????????? ?? ?????????, ?/????
  ???????-??????, ????????????, ??????????? ??
  1.5-2 ?? ??????? ????????????.
• ?? ???? ???, ??? ???????????-??????????
  ??????????
• ? ?????????????? ???????? ???????? ?????? 72,
• ????????????? ??? ? 1, ???????? ??????????? ?
  63 , ??????????????? ????????? ??????? ???????

59
??????????? ?????? 1
HLA-DR
CD19
CD 34
CD 38
CD7
CD 9
CD 79?
CD19
Ki 67
CD10
????????????? ?????????? ?????? ?D34, HLA-DR,
?D19, ?D79?, ?D10-/, ?D9, ?D38, Ki-67,
TDT-, ?D45. ?????????? ?????? ?????????????
????????????? ?-?????????? ??????? ??????????????
???????, B I ????????.
60
??????????? ?????? 1
61
??????????? ?????? 2

• ?-? ?.,39 ???, ???????? ? ???????? ?? ?????????
  ??????????? ?? 40
• ??????????? ? ????????? ??????????? ? ??????
  2006 ????
• ? ??????????? ?????????????? ?? 31 ?????????
  ??????????
• ??????? ????????? 12.05.2006 ???????? ?????????
  ? ????????????? ?????????? ? ????????
  ???????????? ??????? ?????? (? 3-5 ??? ??????
  ?????????). ???????????? ??????? ?????? ?
  ??????????????? ?????? ? ?????????? ?????????????
  ??????????? ????????, ?????? ??????? ???????? ?
  2-3 ?????????, ?????? ? ???????????? ?????? ?
  ??????? ? ???????? ?????? ?????????? ??????.
  ?????????????? ??????.???????????? ??????? ?
  ????????????? ?????????. ????.?????? ?????? ??
  ????????? ??????????????? ???????.
• ??????? ?-???????? 41,4 ?/? (46), ????????
  ?????? ????? ?????-????
• ?????????????3??.,
• ??????????????? ????????? ????????? ?? 4.5??
• ????????? 8 ?????? ??? (R-CHOP), ???????? ??
  ??????????.

62
??????????? ?????? 2
CD10
CD38
CD19
CD16.56
CD16.56
CD19
CD138
CD45
?????????? ?????? ????????????? ? ??????????
??????? ????????????? ???????????????
????????????. ????????????? ?????????? ??????
?D138, CD38, ?D56, ?D13, ?D71, ?i-67,
CD45.
63
??????????? ?????? 3
CD 79a
Ki 67
CD3
Ki 67
64

?????????? ??????? ??????????
?????????? ???????? ??????? (????????? ??????,
?????????? Bcl-2 ? Bcl-x(L)) ?????????? ??????????

CD55, CD46, CD59
?????????? ??????????
???????? ?????????? CD55 ???????? ????????
?????????????? ?????????
?????????? ???????? ???????, ?????????
????????? ???
CD 55 ?????? ???????? ??????????? ??????????
?????????? CD55
1. Wierda W, et al. J Clin Oncol 2005
9833833389 2. Chow KU, et al. Haematologica
2002 873343. 3. Byrd J, et al. Blood 2002
9910381043. 4. Alas S, et al. Clin Cancer Res
2001 7709723. 5. Di Gaetano N, et al. Br J
Haematol 2001 114800809.
65

?????????? ?????????? ????????????
66
???????, ??? ?? ??????????!
67
??????????

• ?????????? ?.?. ? ???????? ?.?. ???????????
  ???????????. ?., 1970 ???????? ?.?. ??????
  ??????????, ?. 12, ?., 1925
• ??????????? ?? ???????????, ??? ???.
  ?.?. ?????????, ?., 2002
• ??????? ?.?. ? ???????? ?.?. ??????????? ?????
  ?????????????, ?????. ??????? ? ???????. ?????,
  1973, ?. 18, ?10, ?, 3, ????????.
• ??????? ?.?. ? ??????????? ?.?. ????????? ??????
  ?????????????, ?., 1977, ????????.
• ?.?. ??????, ?. ????? ???????????? ????????
  ??????. ?., ?????-?????, 2006, 260 ?.
• ?.?.????????????????????????? ??????
  ????????????????? ???????.-?.,2001.-110 ?.

68
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