http://www.upmccancercenters.com

1

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• ??????? ?????? ???????
• ???? ??????? ????? ??????
• http//www.upmccancercenters.com
• ???? 2009

2
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• ???????? ?????? ???? ???? ??????? ?? ??????? ??
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3
??????? ????????? ??????? ??????? ?? ???????
?????????? ??????? (1)

• ????? ?? ?????? ?????? ??????
• ??????????? ??????? ?? ?????? ?????? ??? ??????
• ?????? ???????? ???????? ?????? ?????? ??????? ??
  ??????? ??????? ????????
• ????? ??????? ??????? Molecular carcinogenesis
  (??????? ??????? ?? ??????)
• ????? ??????? ???? ????? ???? ???? ?????????
• ????? ????? ????? ???????

4
??????? ????????? ??????? ??????? ?? ???????
?????????? ??????? (2)

• ??? ????????? ??????? ?????? ????? ??????
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• ??????? ?????? ?????? ????? ????? ?????? ?????
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• ??? ????????? ????? ?????? ?? ????? ????? ??
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5
??????? ???? ???????? ?????? ?? ?????? ?? ???????

• ???? ???????? ?? ????? ?????? ?? ????? 19 ? 21
  ???? ??????? ?? ??????? ???????
• ??????? ?????? ??? ????? ????? ??? ???? ???????
  ?????? ??? ????? ?? ????? (statins) ???? ?????
  ???????
• ??????? ??????? ?????? ?????? ?????? ?? ?????
  ???????
• ??????????? ??????? ?????? ???????

6
????? ????? ???? ??????? ?????? ??? ???? ???????

• ?? ?? 30 ??? ??????? ?????? ??? ??????? ??????
  ?????
• 50 ?? ??????? ??? ??? ??????? ??????? ????????
• ???????? ???????? ??????? ????? ????? ???????????
  ???? ???? ????? ???????? atherogenesis.
• ???? ??????? ??????? ??????? ?? ????? ?????
  ????????
• ?????? ??? ?????? ??? ?? 85 ???
• ?????? ??? ?????? 85 ??? ??? ???

7
UPCI and UPMC Cancer Centers Integrates Across
The Cancer Continuum To Improve Patient Care
Source The Pennsylvania Comprehensive Cancer
Control Plan, December, 2003
8
??? ????????? ??? ???? ??????? ?? ??????? ??
???????

• ??????? ???????? ?? ?????????
• ???? ???? ????? ?????? ?????????? ???????????
  ????????? ???? ????? ?? ????? ????? ?????
• ????? ??????? ?????
• ??????? ??? ???????? ???? ????? ?????
• ???????? ???????? ???????? ???? ???? ??????? ???
  ?????? ????? ??????? ??? ?
• ????? ??????? ?????? (??? ???? ????? ??????
  ???????)
• ????? ????? ???? ?????? ????? ?????? ??????
  ??????? ????????
• ????? ??????? ??????
• ????? ?????? ??????? ?? ?????? ??? ???????
• ??? ???? ??????? ??????
• Modified from Basic Epidemiology, R. Beaglehole,
  et al, 1993

9
?????????? ?? ??????? ???????? ?? ???? ?? ?????
???????
??? ?? 1 ?? ?? ???? ????? ?? ????? ????? ???? ??
???? ???? ???? ???? ??????? ???????
??????? (National Cancer Institute)
10
??????? ?????????? ??????? ???? ?? ????
??????????? ???? ?????? ??????? ??????? (1)

• ????? ?? ????? ????? ???????
• ????? ??????? ????????? ???????? ?????? ?????
  ????? ??????? ?????
• ????? ??????? ?????? ????? ??? ????? ?????
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• ????? ?????? ????? (biomarkers) ?????? ???????
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• ????? ?? ????? ?????????? ?????? ?? ???? ?? ?????
  ????? ???????
• ????? ????? ??????? ???? ??????? ???????
  ?????????? ???????
• ?????? ?????? ????? ????? (radioprotective
  agents)
• ?????? ?????? ???? ???? ??????? ??? ?????? ?????
  (free radical ) ???? ??? DNA ?????? ??? ??????
  ????? DNA ?????? ?????????

11
??????? ?????????? ??????? ???? ?? ????
??????????? ???? ?????? ??????? ??????? (2)

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

12
??????? ?????????? ??????? ???? ?? ????
??????????? ???? ?????? ??????? ??????? (3)

• ????? ????????? ??????? ??????? ?? ???????
• ?????? ? ????? ????? ???????? ????? ???????
  ?????? ?????? ??????? ????????
• ??????? ??????????? (Nutraceutical )
• ?????? ?????? ?????? ??????
• ??? ??????? ??????????? ?????? ???????? ??????
• ????? ?????? ?????? ????? (??? ???? ?? ?????)
  ????? ?????? ??????

13
?????? ??????? ?? UPCI

• ???? ???? ??????? ??????? (Environmental
  Oncology)
• ?????? ????????? ?????? ???????
  (Biochemoprevention)
• ???????? ??????? ??????? ?????? ??????? ?
  ???????? ??????? ?? ???????

14
?? ?? ??? ??????? ???????

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

15
???? ??? ??????? ??????? (CEO)
??? ?? ????? 2004 ?? ???? ??????? ????? ??????

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

16
???? ??? ????? ??? ??????? ???????
17
?????? CEO ????????

• ?????? ????????
• ????? ?????? ??????? ??? ????????? ??????? ?
  ???????? ??????? ?? ??????? ????????? ???????
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• ????????? ???????? ??????? ??? ?????? ????????
  ??????? ???????? ?????? ??? ???????
• ????? ?????????
• ???????? ?????? ??????? Biochemoprevention
• ??????? ?????? ?????? ?????????
• ??? ?????????? ?????? ???? ??????? ?????? ???????
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18
?????? ?????? ??? ?? ?????? ?????? ??? ???????

• ???????
• ??????
• ?????? ?????? ???????
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19
?????? ??????? ????? ????? ??????? ?? ??????

• Cyclophosphamide
• Diethylstibesterol (hormone analog)
• Leather and wood dust ?????? ????? ?????
• Mustard gas??? ??????
• Neoprene
• Nickel compounds
• Nitrosamines
• Radiations (ionizing, ultraviolet,
  radiofrequency) ??????? (??????? ? ??????? ???
  ????????? ? ?????? ?????????)
• Tobacco smoke ???? ?????

• Acrylonitrile
• Aflatoxin
• 4-Amino biphenyl
• Arsenic???????
• Benzene ?????
• Benzidine
• Beryllium
• ?-Naphthylamine
• Bis(chloro)methylether
• Chromium compounds
• Coal tar (aromatic hydrocarbons) ????? ?????
  ??????
• Vinyl chloride

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

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

21
????? ????? ?????? ????????? ????? ???????
??????? Pediatric Head CT Scans-2008

• ??????
• ????? ??????? ??????? (Pediatric CT Scans) ??
  ?????? ??????? ?? ???????
• ????? ??????? ?? ?????? ????? ?????? ??????? ??
  ??????? ???????
• ????? ??????? ??????? (Pediatric CT Scans) ?????
  ?? 200 ??? 6000 ?????? ??????? ?????
• ???? ???? ??? ?? ???? 2008 ?? UPCI ?? ?????
  ??????
• ?? ????? ????? ???? ????? ?????? ??????? ????????
  ? ????? ???????? ??????? ??????? ??????? ?? ???
  ????? ??????? ???????? ?? ?????? ???? ?? ??????

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

• ?????? ?????? (Hardell et al Int. J of Oncology.
  28509-518, 2006)
• ????? ????? ??????
• OR2.9 (CI 2.0-4.3 analogue cell phone), OR1.5
  (CI1.1-2.1 digital cell phone) OR1.5-fold (CI
  1.04-2.0, cordless phone)
• ????? ????? ?????? 15 ??? 15 years OR3.8 (CI
  1.4-10 analogue cell phone)
• ?????? ??????? ? 11 ????? ?????? ???? 10 ?????
  ???????? ??????? ???????? ????????? Hardell et
  al. Occ Env Med. 64626-632, 2007.
• ????? ?? ????? ????? ?????? (4 ?????? ??? ?????
  ???????)
• ????? ?? glioma (4 ?????? ??? ????? ???????)
• ?????? ???????
• ????? ????? ?????? ipsilateral)) (OR2.4 CI 1.1-
  5.3)
• ????? Glioma (OR 2.0 CI 1.2-3.4)
• ?????? ??????? (Hardell et al. Int J of Oncology,
  321097-1103, 2008)
• 6 ?????? glioma 10 ????? ? ?4 ??????
  ipsilateral OR2.0 (CI 1.2-3.4)
• 4 ?????? ?????? ????? ?????? 10 ?????
  ipsilateral OR2.4 (CI 1.1-5.3)
• ?????? ??????? Kan et al. J Neurooncol 8671-78,
  2008, UTAH study
• 5 ?????? ?????? ??? ??????? ??????? ???????? 10
  ????? ??? ?????? OR1.25 (CI 1.01-1.54)
• INTERPHONE (????? 2008)
• ????? Glioma ipsilateral OR1.39 (CI 1.01-1.92)
  Nordic study (Lahkola et al, 2007)

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

• ????? ?????? ???? ???? ?????? ????????? ???????
  ?? ??????? ??????? ??????? ??? ????? (?????? GSM
  900 Mhz ) ??? ?????? ????? ?????? ??????? ??? ??
  ?????? ?? ?????? ??????? (??????) Absorption Rate
  in W/kg))
• Gandhi, O.P.G. Lazzi, and C.M. Furse,
  Electromagnetic Absorption in the Human Head and
  Neck for Cell Telephones at 835 and 1900 MHz.
  IEEE Transactions on Microwave Theory and
  Techniques, 1996. 44(10) p. 1884-1897

24
 ??????? ??? ???? ?????? ??????? ?????? ??????
??? ????? ?????? ????? ?? ???????? ??? ????? ???
????? ?????? ? ??? ??????? ?????? ?????? ?????
?? ???? ?? ????? ? ????? ??? ??????? ???????
25
????? SLER ?GLIOMAS ??? ?????? ????? ??? ?????
?????? 0-39 ??? ?? ?????
26
????? ??????? ?????? ?????????? ????? ?????
?????? ????????

• ????? 2008 ?????? ??????? ? ??? ??????? ?? UPCI
  ?????? ?????? ??? ???? ????? ????????? ??????
  ??????? ? ???? ????? ??? ?????? ?????????? ??????
  ????? ?????????? ??????? ????? ??????? ??
  ??????? ??????? ???????? ? ???? ??? ???? ??
  ???????? ?????? ????? ?????? ???????
• ???? ????? ??????? ?? ??????? ???????? ????? ????
  ???? ??? ?????? ? ?? ????? ??????? ???? ????
  ?????? ???? ?? ??? ?????????
• ????? ???? ????? ??????? (????? ?????? ????????
  ?????)
• ????? ????? / ?????? 2008 ?????? ??????? ??
  ???????? ??????? ?????? ???? ???????? ?? ?????
  ???? ????? ?????? ??????? ? ??????? ???????
  ????????? ????????? ???? ??????? ??????? ???
  ????? ?????? ?? ????????
• ????? ????? / ?????? ? 2008 ????? ?????? ???
  ?????? ??? ??????? ?????? ???? ????? ?? ??????
  glioma ????? ??????? ?????? (????? ????? ?????)
• ????? / ?????? 2009 ?????? ?????? ?? ???????
  ????? ??? ??? ??????? ???????? ???????? ????????
  ??????? ?????? UPCI ? ???? ????? ????????
• ???? ??? ??? ?????? ???? ?? ??????? ????? ???????
  ????????? ?? ?????? ?????? ????? ??????? ??????
  ?????? ???? ???? ?????

27
????? ??????? ???????????? ???? ?? ????????????
??????

• ??????? ??????? (Pediatric CT Scans)
• ????? ????? ??? ?????? ???????? ??????? ??????
  ????? ?? ??????? ???? ?? ????? ?? 200 ??? 6000
  ???? ????? ??????? ???????
• ???? ??? ????? ???? ?? ????? ??????? ? ???? 2008
  ? ?? ????? ???? ????? ?? ?????? ???? ??????? ??
  ?? ??? ??????? ??????? ??????? ???????
• ??????? ???????? ?????? ??????
• ??????? ???????? ???? ???????? ??? ?????? ??????
  ???? ??????? ??????? ???????? ??? ????? ?????? ??
  ????? ??? glioma ?????? ????? ??????
• ??? ????? ?????? ??? ???? ??????? ????????? ??
  ???? ??????? ?? UPCI ? UPMC
• ????? ????? ?? ???? ?????? ?? ???????? ????
  ?????? ???????? ??????? ?????? ????? ???????
  ????????
• ??????? ?????? (??? ??????? ?? ??????? ??????)
• ????? ??????? ?????? ?????? ?????????
• UPMC ? ????? ??????? ????? ????? ?? ??????? ??
  2007
• ?? ??? 2007 ?? ??? ??? ??? ??????? ?? ???????
  ???????? ???? ???? ?????? ?????? ?? ??????? ??
  ??????
• ?? ??? ??? ????? ?? 2008 ??? ????? ?????????
• ???????? ????? (?????? ?? ????? ????? ???????
  ????????? ?? ??????????) ?????? ????? ??????
  ??????? ??? ????? ?????????? ???? ???? ?????
  ???????? ??? ???????? ?????? ???? ????? ??????
  ??????? ???? ????? ??????
• ??? ???? ??????? ???????? ????? ??? ?????? ??????
  ???? ????? ??????

28
?????? ?????????? ???? ?????? ?????????? ???????
(Xenoestrogens)

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

29
???????? ???????????? ???? ??? ????? ????? ?????
?????
Quantitative BrdU assay, dark spots indicate high
DNA synthesis
30
???????? ????? (Xenobiotic) (? ?) ???? ?? ????
?????? ?? ???????? ???????????? An indirect
assay through measuring the effects on MCF7
breast cancer and on A549 lung cancer cells -
Talal El-Hefnawy
31
?????? ???????? ?????? ??????? (Biochemoprevention
) ???? ??????? ?? ????? ??????
32
?????? ?? ??? ???????? ??????? ??????? ?? ???????
(1)

• ??????? ?? ??????? ??????? ??????? ?? ?????
  (organosulfur compounds)
• ????? ?????????? (????)
• ???????? ????? ???????? ????? ????? (????)
• ??????? ?? ??????? ?? ???? ?????? ??????? ??
  ???????? (cruciferous vegetable-derived
  isothiocyanates)
• ????? ?????????? (????? ??????)
• ????? ????? (???? ??????)
• ????? ????????? (??????????)
• ????? ????? ??????? (??????? ?????)
• ??????? (????)
• ?????????? (????? ?????)
• ????? ??????? ???????
• ??????????? (?????? ??????) ??????
• ????????????

33
?????? ?? ??? ???????? ??????? ??????? ?? ???????
(2)

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

34
Inhibition of PC-3 Xenograft Growth by
Garlic-derived Diallyl Trisulfide (DATS)
A
C
B
DATS (5 µmol) was given orally three times/week
P lt 0.05 by Students t-test. Shivendra Singh
35
??????????? (Resveratrol) ???? ????? ?????? ?????
?? ????? ??????
??????? ???????? ????? (50-100 ???/ ??)
?????? ?????? (1-3 ???? / ???) ????? ????????
???? ????? Polygoum cuspidatum
36
Resveratrol ???? ???? ??????? ?????????
DMBA-induced skin cancer model. 0, 1, 5, 10, or
25 µmol of RSVL plus 5 µmol of TPA ??? ????? ??
?????????? ????? ??????? ?????????
Copied from Jang et al, Science, 1997 Shivendra
Singh
37
??????? ????????? ???? ???? ?? ??? ??????? ??
??????? ???

• ???????? ??????? ?UPCI
• ????? ??????? ??????? ?? NSABP Polyp
• ????? celecoxib ???????? ???? ????? ??????
  ?????? ????? ?? ?????? ?????
• ????? ?????? ? ductal epithelium
• ????? ??????? NSABP STAR
• ????? Muc1 ??????? ?? ????? ???????

38
?????? ????? ???? ??????? ?? ????? Celecoxib
??????? ?? ????? ?????

• ??????? ?? ???????
• ?????? ?? ???????? ?????????? COX-2? ????????? ?
  ????????
• ?????? ?? ????? ??????? ??????? (???? ???? ????
  ??? ???????? ???????? ????? ??? ????? ?? ????????
  ?? 20 ??? ?? ???????? ??????)

39
MUC1-Poly ICLC (HiltonolTM) ???? ??????? ?? ?????
?????? ?? ????? ????? ???????? Robert Schoen
Olivera Finn
40
???????

• ??????? ????????? ??????? ?? ????? ????? ASA,
  COX2, vitamins
• ?????? ???????
• ??? ???
• ???? ??????
• ????? ??? ??????? ? ??? ???? ??????? ???????
• ?????? ???? ?? ???? ???? ?????? ??? ?? ???? ?????
  ??? ????? ????????? ????????

41
?????? ??????? Muc 1 Immunotherapy in CRC

• 32 ????? ? 527 ????
• ????? ?????? ????? ??? ?????? ???? ???? ?????
  ??????
• ??????? ??????? ??????? 59????????? 44
• ????????? ???????? 10-14

Nagorsen, Clin CA Res 2006123064
42
????? ????? ??????? ??????? ???????? ?

• ??? ????? CRC
• ???? ????? ???? ??????? ????????
• ?????? ???? ???? ????? ?????? ??? ????
• ???? ????? ??????
• ???? ????? ???? ??????

43
???????
???????

• ????? ????????? ???????? ?MUC1 - ???? ICLC

????????

• ??? MUC1 isotypes IgG, IgM
• ??? ?????? ????????
• ????? ??????? ????????? ??? ??????? ?????? MUC1
  ????? ????? ??????

44
?????? ???????? ??????? ???????? ???? ????
???????? ??????? -- ???????

• ???????? / ????????? proteomics and metabolomics
• ????? ?????? ????? ?????????? ???? ???? ???????
  ???????? ?? ???????? ????????? ???????? ???????
  ??????????
• ????? ?????? ????????? ?? ????? ?? ??????
  ??????? ?? ????? ????? ???? ??????? ???????? ??
  ???????? ?????????
• ???????? / ????????? ??????????
• ????? ?????? ?????? ?? ????? ?????? ???????? ????
  ???? ??????? ???????? ?? ???????? ?????????
• ??????? ????? ???????? ??????? ?????? ??? ??
  ???
• 1. ????? ?????? ??? ??? ?????? ??????
• 2. ???????? ???????
• 3. ??? ????????? ?????? ??????? ????????

45
?????? ???????? ??????? ?? UPCI

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

46
???????? ??????? ???? ?????? ?????? ??? ?????
???????? ??????? ???? 4 SN90
SP98 ???????? ??????? ????? 3 SN100
SP100

Anna Lokshin
47
????? ??????? ?????? ?????
???? ???????? 98 ???? ???????
94 SENSITIVITY 98 SPECIFICITY
94 Prolactin, HE4, CA 72-4, MMP-3, and FasL
Anna Lokshin
48
??????? ???????? ?????? ???????? ??????? ????????
??? 4 ??????? ??????? ?? ???????

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