Cancer Stem Cells

1
ME???????? ??????? ?? ?????????? ????????
????????? ??????
?????????? ?????? ? ?????? ????????? ?????
????.??. ?????? ????????, ??????
2
?????????? ?????? ? ?????? ????????? ?????
???????? ????? ?? ????? ??????????? ?????????
?????? ??? ?????????? ?????????, ??? ? ??????
?????? ? ???? ?? ???????? ?????????, ????? ??
???.
3
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????? ??????? ???????? ???? ???????? ?? ????????
? ????????? ?????????, ?? ?? ????????? ??
???????? ???????? ????? ???????? ????????
???????, ????? ?? ?????????? ???????????? ?????,
??????????? ????????????? ? ????????????? ??
??????.
4
?????????? ?????? ? ?????? ????????? ?????
U???????? ????? (????? ???????? ?????) ????? ??
????? ????? ?? ??????????? ???????. ????????
???????? ??? ????. ??? 1.3 ??????? ???? ??
??????????????, ? ??? 465,000 ????? ????? ??????
? ?????.
American Cancer Society (2006)
5
????????? ? ?????????? ????????? ????? ? ????? ????????? ? ?????????? ????????? ????? ? ????? ????????? ? ?????????? ????????? ????? ? ?????
????????? ??????????
???????????? ?????????????????????????????????????????? ??????????????????????????????? ????????? ????????????????????????? 18.71919.132.74648.774.481.783.284.386.787.287.888.791.9101.1 5.514.110.48.314.115.818.919.818.421.127.524.317.327.821.519
American Cancer Society (2006)
6
?????????? ?????? ? ?????? ????????? ?????
?????? ????? ???? ????????? ????? ? ??? ???????
????? ?? 1990, ?????????? ????? ???????????? ?
????? ??????? ???????. 40.910 ??????? ?????????
????? ???????? ??????? ??????? ? 2007 ???????
???. ???????? ????? ?? ??????? ?????????????
???????
American Cancer Society (2006)
7
??????? ??????
??????? ???
????????? ???????? ????????? ????? ????? ????????? ??????? ? ???????? 10 ?????? ????????? ???????? ????????? ????? ????? ????????? ??????? ? ???????? 10 ??????
20 ??????30 ???????? 40 ???????? 50 ??????    ?? 60 ???????? 70 ??????????? 70 ??????   1 ?? 1.985  1 ?? 229  1 ?? 68  1 ?? 37  1 ?? 26  1 ?? 24  1 ?? 8
????? Among those cancer free at age interval.
Based on cases diagnosed 2000-2002. "1 in" are
approximates. Source American Cancer Society
Breast Cancer Facts Figures, 2005-2006.
8
??????? ??????
????????? ??? ???????????? ????????? ?????????
????? 1,5 ?? 3 ???? ???? ????????? ??? ?? ?
????? ??? ?????? ???????? ?????? ???? ?????????
????? 32 ??? ????????? ????????? ????????
5-10 ??? ?????? ?????????? BRCA1 ? BRCA2 -
???????? ???????? ????? ? ??????-
9
??????? ??????

• ???????????? ?????????????? ???????? ?? ???????
  ??????????? BRCA1 - BRCA2
• ?????? ????????? ????? ? ????? ???????? ????
• ???????? ??????? ? ????? ???????? ????
• ?????????? ???????? ?????
• ????????? ???????? ?????? ????????? ??????? ?
  ?????
• ???/???? ?????? ????? 50 ?????? ?? ??????????
  ?????
• ?????? ????????? ?????? ? ????? ??? ???????
  ????????
• ???????? ????? ??? ?????? ??????? ????????
• ?????/???? ??????? ???????? ?????????? 50 ??????
  ?? ?????????? ?????

10
??????? ??????

• ????????????? ????????
• (????????? ???????????)
• ??????????? ??????? ????? ????????? ? ?????
  ?????????? ??????? ???????? ??????????? ????????
  ????????? ?????.
• ????????? ????? ?? ???? ??? ???? ???? ????? ?
  ????????? ??? 45 ?????? ??????. ???????? ?? ?????
  2 ?? ????? ?????? ?? ????????? ???????.
• ????????? 1,4 ???? ?????????? ? ?????? ??
  ???? ???? ?? ??????.

11
??????? ??????
????????? ??? ???? ???? ??? ????? ??????? ?
???????? ???????? ??????. ???????? ??????????
????? ?? ???????? ????????? ?????. E??????????
??????????? ????????????? ??????? ????????????
????????????? ??????? ???? ???????? ?????????
?????????? ?????? ????? ????? ? ?????????
????????? ?????. ???????? ??????????? ????????
?????? ????????? (????????? ???? ???????? ?????
??????, ????????, ??????? ? ???????? ?).
12
??????? ??????
????????? ?????????? ???????? ????? ?? ????????
????? ?????????? (??????? American Cancer Society
je ???????? 495.477 ???? ????? 16
??????) ????????? ????? ??? ????? ? ???? ??
???????? ????????? ????????? ???? ?????????
???????????? ??????? ?? ????????? ????????.
13
??????? ??????
?????????? ?????? ??????? ??????? ????? ?????
???? 1,9 ???? ??? ??????????????? ??????
????????????? ?????????? ????? ???? 4,4 ???? ???
???????? ???????????? ??????????? ???????????
??? ????? ?? ??????? ?????? ?????? ????????????
??????? ???????? ?? ??????? ??????? ????????
?????????
14
TNM ????????????? ? ????????? ????????? ?????
???????????? ??? ????????? ????? ???????????? ??? ????????? ?????
  5 ??????  10 ??????  15 ??????  20 ??????   88  80  71  63
Source American Cancer Society
????? American Cancer Society
15
TNM ????????????? ? ????????? ????????? ?????
???????? ?????? (?) ????????? ? ??????? ????????? (N) 5-??????? ????????????
lt 2 cm 0 1 3 4 96 87 66
2 5 cm 0 1 3 4 89 80 59
gt 5 cm 0 1 3 4 82 73 43
?????????? ????? Carter AL, Allen C, Henson DE, et al. Relation of tumor size, limph node status, and survival in 24.740 breast cancer cases. Cancer 63 181, 1989 ?????????? ????? Carter AL, Allen C, Henson DE, et al. Relation of tumor size, limph node status, and survival in 24.740 breast cancer cases. Cancer 63 181, 1989 ?????????? ????? Carter AL, Allen C, Henson DE, et al. Relation of tumor size, limph node status, and survival in 24.740 breast cancer cases. Cancer 63 181, 1989
16
Stage Tumor (T) Node (N) Metastasis (M)
0 Tis N0 M0
I T1a N0 M0
IIA T0 N1 M0
  T1a N1 M0
  T2 N0 M0
IIB T2 N1 M0
  T3 N0 M0
IIIA T0 N2 M0
  T1a N2 M0
  T2 N2 M0
  T3 N1 M0
  T3 N2 M0
IIIB T4 N0 M0
  T4 N1 M0
  T4 N2 M0
IIIC Any T N3 M0
IV Any T Any N M1
17
TNM ????????? ? ????????? ????????? ?????
???????? 5-??????? ????????????
0 100
I 100
IIA 92
IIB 81
IIIA 67
IIIB 54
IV 20
Source American Cancer Society
????? American Cancer Society
18
?????????? ?????? ? ?????? ????????? ?????
??? ????????? ????????? ?? ???????? ???????
???????? ?????? ???? ???? ??????? ?????????? ??
???????? ?? ???????? ??????? ????????????? ?
????????? ?????????
19
?????????? ?????? ? ?????? ????????? ?????
????????? ??? ??????????? ????? ? ??????????

• ???????? ?????????????? ??????
• ?????? ?????????? ????? ???? ????? ?????? ????
  ?? ????????? ????????? ??????????? ??? ??????????
  ??????????? ???????? ???????????

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

• ????? ????????? ? ???????? ???????? ??????
• ?????????? ?????????
• ?????????? ????????? ????????? ??????? (staging)
• ?????? ????????? ???????
• ?????????
• ????????? ?????????? ????????? ? ??????? ???????
  ????????? ???????

21
?????????? ?????? ? ?????? ????????? ?????

• -???????????
• ??????????? ???????? ????????? ? ??????????
  ?????????? staging-a ????????? ??????? ??? ??
  ????? ?? ????????? ?????? ?????????? ? ????????
• ???????? ???????????? ????????? ???????
• - ???????????? ???????? ???????? ???????????
• - ???????????? ?????????? ???????? ???????????
• - ???????????? ??????????? ????? ??????????
  ???????
• ??????? ??????????? ???????? ??????????
  ?????????

22
?????????? ?????? ? ?????? ????????? ?????

• ?????????????? ??????
• ????????? ??
• ??????? ?????? ????? ???????? ??????? ? ????????
• ????????? ?????? ? ?????? ????????? ? ???????
  ??????

23
?????????? ?????? ? ?????? ????????? ?????

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

24
?????????? ?????? ? ?????? ????????? ?????
?????? ????????? ????? ????????? ?????????
????????? ?????
25
BRCA1
??????? ??????
???????? ?????
????????
??????????????
???
????????
??????
?????
????????????
????????
????????
CA-125
???????????
26
?????????? ?????? ? ?????? ????????? ?????
??????? ???????? ????????? ????? ???????????? ???
????????? ?????????? ???????? ????????? Me????
?? ??? ??? ?? ???????? ?? ???????? ??????? ?
????? ? ? ?????? ???? ??????? ????.
27
?????????? ?????? ? ?????? ????????? ?????
??????? ? ?????????? ?????? ????????? ????????
??????? ???????? ??????? ?????????? ?????????
???????? ????????? ??????. ????????? ???????? ??
???????? ?? ????????? ???????? ??????? ???????.
28
?????????? ?????? ? ?????? ????????? ?????
??????? ???????? ??????? ?????????
????? ????????? ???????????? Halsted
(1894) ???????????? ????????? ????????????
??????? ???????????? ?? ??????????
?????? Patty, Madden ????????? ????????????
????? ????? ? ????????? ?????? ????? ?????
29
?????????? ?????? ? ?????? ????????? ?????
??????? ???????????? (simple mastectomy) ????????
????????? (Tylectomia) ?????????? ?????????
?????, ??????? ???????? ????? ?? ????????? ?? 3
5 ?? ? ?????? ????????????? (segmentalna
mastectomia lumpectomia)
30
?????????? ?????? ? ?????? ????????? ?????
????????????? ????????? ????????? ?????
????????????? ?? ?????????? ?????? ?ylectomia ??
?????????? ??????. ?????? ???? ?? 4 ?? ??
?????????? ??????? ?????????, ??? ????? ?????????
???????? ?? ??????? ???????? ???? ??????????????
?????? ????????. ??????? ?? ? ?????? ???????
???????? ????????? ???????? ?? ??????????
?????????????. ????????????? ?? ???????????
????????? ?? ???????? I ? II? (T1-2 NO MO)
31
Breast-Sparing Surgery with Radiation versus
Mastectomy 1995 National Cancer Institute Update
Conference
Deaths/Patients Deaths/Patients
Study BCT with RT Mastectomy Difference
Denmark 90/430 77/429 None
EORTC 107/456 89/422 None
Institut Gustave Roussy 17/88 18/91 None
NCIBethesda 14/121 17/116 None
NCIMilan 74/352 84/349 None
NSABPa 176/515 188/492 None
Total 478/1962 473/1899 None
BCT, breast-conserving treatment EORTC, European
Organization for Research and Treatment of
Cancer NCI, National Cancer Institute NSABP,
National Surgical Adjuvant Breast and Bowel
Project RT, radiotherapy. aSt. Luc Hospital data
excluded.
32
?????????? ?????? ? ?????? ????????? ?????
????????? ????????? ????? ??? ????? ?? ??????
????????? ???????? ??????.
???????? ?N?
0 Tis, N0, M0
I ?1, N1, M0
I T0, N1, M0
IIA T2,N0, M0
IIA T2N1, M0
IIB T3 ???? o? 5 cm N0,M0
IIB . T3 ???? ?? 5 cm N1, ?0
33
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34
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35
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36
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37
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38
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39
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40
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41
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42
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• ? ???? ???????????? ???? ?????????
• (???? ?????? ????? ??? ??????????? ????????????
  ????????? ??????????? ?? ??? ???? ???????)
• ????? ??? ?????? ?? ??????? ??????
• ??????? ???? ???????? ?????????? ?? ????? ? ????
  ???? ??? ??????,
• ?????? ??????? ????????,
• ???? ?????? ???????? ???????????????

43
?????????????? ?????
44
BRCA1
??????? ??????
???????? ?????
????????
??????????????
???
????????
????????????
?????
??????
????????
????????
CA-125
???????????
45
BRCA1
??????? ??????
???????? ?????
????????
??????????????
???
????????
????????????
?????
??????
????????
????????
CA-125
???????????
46
BRCA1
??????? ??????
???????? ?????
????????
??????????????
???
????????
??????
????????????
?????
????????
????????
CA-125
???????????
47
Klinicki pregled
Klinicki pregled
Palpatorni nalaz pozitrivan (Tumor
dvodimenzionalni ili trodimenzionalni)
Palpatorni nalaz (Tumor dvodimenzionalni ili
trodimenzionalni)
MAMOGRAFIJA ( do 40 godina UZV. pregled )
MAMOGRAFIJA ( do 40 godina UZV. Pregled )
Uredan nalaz
Suspektan nalaz
UZV pregled
Citologija Core biopsija vodena UZV/Rtg
Uredan nalaz
Suspektan nalaz
Citologija ili core biopsija
Suspektan nalaz
Uredan nalaz
Suspektan nalaz
Operativna histologija
Operativna histologija
Kontrola za 6 meseci
Kontrola za 6 meseci