lung cancer detection life - mitweb.mit.edu/7.01x/7.013/documents/7.013lect31.pdf · ( e.g and...
TRANSCRIPT
STARTSTARTFOUNDATIONSFOUNDATIONS
How-to 1How-to 1 FO
RM
AT
ION
FO
RM
AT
ION
How-to 2How-to 2
SYSTEMSSYSTEMSPR
OB
LE
MS
PR
OB
LE
MS
BIOCHEM GENETICS GENOMICSMOL. BIO
STEM
CELLS,
CLONING
REC. DNA
CELL TYPE
3DSTRUCTURE
CELL BIOL
VIRUSES
CANCER
HUMAN
DISEASE
LIFELIFE
NERVOUS
SYSTEMS
BIOLOGY FUTUREFUTURE
SYSTEMS
BIOLOGY
Lung cancer detection
Lung masses evident on chest X-ray Lung masses evident by computedtomography (CT)
Slide 2 - 7.013 - 4/27/07
Leukemia is a overabundance of abnormal
cells in the blood
Leukemic cells in a blood smearNormal blood smear
Slide 3 - 7.013 - 4/27/07
Colon Cancer Progression
Normal colon(endoscopy)
Colon polyp Colon carcinoma
Section of colonwith carcinoma
(circled)
Slide 4 - 7.013 - 4/27/07
Hyperplasia
Benign Tumor
(e.g., an adenoma)
In Situ Cancer
(e.g. an adenocarcinoma
bloodvessels
Advanced Primary Cancer
(locally invasive)
basementmembrane
stem/precursor cells
Normal Tissue
Cancer develops in stages
MetastaticSpread
Steps in Tumor Progression
*Scale bar equals 50µM
Atypical Adenomatous Hyperplasia (AAH) Adenoma Adenocarcinoma
high magnification high magnification
chromosomes of a
normal cellchromosomes of a
cancer cell
Chromosomal Abnormalities are Common in Cancer Cells
Slide 7 - 7.013 - 4/27/07
Causes of cancer: compounds that are morecarcinogenic are also more mutagenic
Inference: cancer cells are likely to carry mutant genes
More potent mutagen
More
Potent
carcinogen
Slide 8
7.013
4/27/07
Conversion of benzo(a)pyrene to mutagenic epoxides
O B(a)P 7,8 epoxide
OH
OH
OH
OH
O
Cytochrome P450
(metabolic enzyme
in liver)
Epoxide hydrolase
P450
B(a)P 7,8 dihydrodiol(+(anti))B(a)P
7,8 dihydrodiol 9,10 epoxide
Benzo(a)pyrene (B(a)P)
Slide 9 - 7.013 - 4/27/07
Tobacco Use in the US, 1900-1999
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
1900
1905
1910
1915
1920
1925
1930
1935
1940
1945
1950
1955
1960
1965
1970
1975
1980
1985
1990
1995
2000
Year
Pe
r C
ap
ita
Cig
are
tte
Co
ns
um
pti
on
0
10
20
30
40
50
60
70
80
90
100
Ag
e-A
dju
ste
d L
un
g C
an
ce
r D
ea
th
Ra
tes
*
*Age-adjusted to 2000 US standard population.
Source: Death rates: US Mortality Public Use Tapes, 1960-1999, US Mortality Volumes,
1930-1959, National Center for Health Statistics, Centers for Disease Control and
Prevention, 2001. Cigarette consumption: Us Department of Agriculture, 1900-1999.
Per capita cigarette consumption
Male lung cancer death rate
Female lung cancer death rate
Slide 10
7.013
4/27/07
chromosomes of a
normal cellchromosomes of a
cancer cell
Chromosomal Abnormalities are Common in Cancer Cells
Slide 11
7.013
4/27/07
Clonal Evolution Theory of Tumor Development
1
1,2
1,2
1
1
1
1,2,
3
1,2,
3
1
1
1,2,
3
Numbers represent sequential mutations to cellular genes
Slide 12 - 7.013 - 4/27/07
Clonal Evolution Theory of Tumor Development
Cancer-associated mutations
affect:
-proliferation
-cell death
-angiogenesis
-cell motility
-invasion
-other
1
1,2
1,2
1
1
1
1,2,
3
1,2,
3
1
1
1,2,
3
Slide 13 - 7.013 - 4/27/07
Tumors and Angiogenesis
Carmeliet and Jain. Nature (2000) 407:249.
Somatic mutation
Proangiogenicfactors secreted
by tumor andstroma
Tumor growth andmetastasis
Smallavascular
tumor
= Angiogenic inhibitor
= Proangiogenic factor, VEGF
Slide 14 - 7.013 - 4/27/07
Hyperplasia
Benign Tumor
(e.g., an adenoma)
In Situ Cancer
(e.g. an adenocarcinoma
bloodvessels
Advanced Primary Cancer
(locally invasive)
basementmembrane
stem/precursor cells
Normal Tissue
Cancer develops in stages
MetastaticSpread