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Realizing Individualized Cancer Therapy
Effects of intra-operative ischemia on cancer and n ormal tissueProf. Dr. Hartmut Juhl
CEO of Indivumed GmbH and Inostics GmbHAdjunct Professor, Georgetown University and Hamburg University
www.indivumed.comjuhl@indivumed.com
Hamburg:
A Federal State of Germany
Germany‘s 2nd largest city
Metropolitan area of ~ 4 Mio people
Highest income/citizen in Europe
„Happiest citizen in Germany“
High density of outstanding cancer clinics
Indivumed GmbHHamburg, Germany
Founded : 2002 Inostics GmbH
B. Vogelstein et al. (JHU)
F.Diehl/H.Juhl
Indivumed Group
IndivuTest GmbH
Employee: 90
Financing: Private
Founded : 2002
Indivumed Inc.Kensington, MD
Founded: 2005
Inostics GmbHHamburg, Germany
Founded: 2009
Inostics Inc.Baltimore, MD
Founded: 2010
IndivuTest GmbHHamburg, Germany
Founded: 2011
Indivumed Vision: Individualizing Cancer Medicine
• Clinical Integration
• Biobanking
Therapy 1 Therapy 2 Therapy 3
•Tissue & Blood Based Research
• Protein Based Dx (Indivumed)
• DNA-Based Dx (Inostics)
• Patient Testing (IndivuTest)
Indivumeds Approach:Integration of Research, Surgery and Patient Care
+ Indivumed Clinical Team
Indivumed Scientific Team++++++
+Biospecimen• Tumor tissue• Normal Tissue• Blood• UrineData• Processing Data• Clinical Data• Follow-up Data
Scientific Team
Tumor-Biobankand
Clinical Data Base
BiospecimenDirect Processing
++++++++++Partner
Hospitals
Indivumed Solution:Integration of Clinical Care, Biobanking and Research
Tumor-Biobankand
Clinical Data Base
Indivumed Standard of Biobanking:
� Exact documented and very short tissue cold ischemi a times of < 12 min (mean 7 min)
� Exact tissue localization and standardized fixation
� Complete biospecimen sets
10 min
Tissue ischemiaand protein
phosphorylation
� Highest tissue quality monitored by visual inspectio n, H&E staining and microscopic assessment
� Native and rapid fluid preparations
� Complete specimen data
� Complete clinical data
� Patients’ confidentiality assured following internat ional standards
10 min
20 min
60 min
Target Validation&
Pathway Analysis
Business Concept
ServiceBusiness
Biomarker(Co-)Development
Understanding Differences between
Patients
Protein-BasedTissue Diagnosis
(Indivumed)
Clinical Integration of
Research
Biobanking
BusinessPatient
Care
DNA-BasedDiagnosis(Inostics)
Understanding the Molecular Basis of Cancer: Status 19 71 (Nixon Declares „War Against Cancer“)
Understanding the Molecular Basis of Cancer: Status 2011
Understanding of Cancer Pathways as Basis for„Targeted Therapeutics“
„Targeted Therapies“ are the Focus of Current Drug Devel opment
Targeted therapies53%
Vaccines14%
Antihormonaltherapies
1%
Cytotoxics22%
Genetherapies
4%
Immuno-therapies
5%
PDT0.3%
Radio-therapeutics
1%
Cost of 900 Mio $ / new FDA approved compound
90% of compounds fail in clincial phases
Ca. 60 „Targeted Therapies“ are Approved and >800 Compounds are in Clinical Trial
(Status 2012/01)
Analysis of Pathway Activity for Individualizing Cancer T herapy
Targetexpression?
Relevant for cell biology? (aktiv yes/no)
Which Drug?(=Inhibitor)
DNA mRNA Proteins Protein Modifications(e.g., phosphorylation)
MutationsKRASPIK3CABRAF
Target-ExpressionHER-2EGFRVEGFR
FunctionalitypmTORP-AKTP-MAPK
Predictive Biomarker: High Predictive Value or Robustness?
MutationsOncotypeAmpliChipMammaPrintBRAF
EGFRMany others
VEGFROthersProtein Profiling
P-MAPKMany, many more
Predictive value / Impact of preanalytical factors
MammaPrintOthers
Diagnostic Approaches for Individualizing Cancer Therap y:Tissue and Blood
TumorTissue Blood
• Free Tumor DNA•Tumor cells (CTC)•Proteins•Metabolome•RNA (microRNA)
Frozen orFFPE
Tissue
ViableTissue
Reflects high complexity of tumorDifficult to obtain at time of therapyQuality matters a lot
Only low complexity of tumorStatus at time of therapyAllows monitoring and repeated testing
Specimen is viable and reactive Biomolecules may degrade
Time 0
Cancer Problem #1 for Predictive Biomarker and Drug Dev elopment: :Availability of Tissue that Reflects Reality of Tumor Bio logy
Patient andPresurgical therapy
Medical/SurgicalProcedures
AcquisitionProcessing
StorageTemperatur
Handling, Processingand analytical assays
Expression of Targets (e.g., Pathways) and Biomarker depend on Individual Variables and Tissue Processing
Specimen is viable and reactive Biomolecules may degrade
Time 0
Cancer Problem #1 for Predictive Biomarker and Drug Dev elopment: :Availability of Tissue that Reflects Reality of Tumor Bio logy
Patient andPresurgical therapy
Medical/SurgicalProcedures
AcquisitionProcessing
StorageTemperatur
Handling, Processingand analytical assays
Expression of Targets (e.g., Pathways) and Biomarker depend on Individual Variables and Tissue Processing
Phosphoprotein Expression:pMAPK Immunostaining (Ventana)
10 min
Case BCase A
Change of pMAPK expression
20 min
60 min
Change of pMAPK expressionafter 10-20 min cold ischemia
Without knowledge about tissue processing and rapid tissu e fixation
protein expression data are unreliable and
understanding of pathway activity is impossible
Specimen is viable and reactive Biomolecules may degrade
Time 0
Cancer Problem #1 for Predictive Biomarker and Drug Dev elopment: :Availability of Tissue that Reflects Reality of Tumor Bio logy
Patient andPresurgical therapy
Medical/SurgicalProcedures
AcquisitionProcessing
StorageTemperatur
Handling, Processingand analytical assays
Expression of Targets (e.g., Pathways) and Biomarker depend on Individual Variables and Tissue Processing
Patients receiving left hemicolectomy
Indivumed data base / biobank:
Time (min) between artery ligation
and tumor removal
Retrospective Study:Impact of Time between Ligation of Main Artery and Tumor Resection
on Gene Expression in Colon Cancer(NCI-Indivumed study)
MesentericMesentericartery inferiorartery inferior XX
20 25 30 35 40 45 50
(min)
Time (min) until freezing
10 min
LCM isolation of tumor cells
Gene expression (Affymetrix)
Bioinformatics
Warm ischemia (min)20 25 30 35 40 45 50
PCA mapping: grouping of warm ischemia time points
202530
Impact of Time between Ligation of Main Artery and Tumor Resectionon Gene Expression in Colon Cancer
(NCI-Indivumed study)
35404550
Prospective trial collecting tissue during surgery
Research Studies on the Effect of Intra- and Post-operat ive Ischemia on Gene and Protein Expression Patterns in Liver (Projec t 1) and Colorectal
Tissue (Project 2).An Exploratory Research Study (29XS111)
Partner:
Funded by NCI Contract No. HHSN261200800001E
Partner:
OBBR/NCI
Indivumed GmbH
Department of Surgery, Israelitisches Krankenhaus (D r. Zornig)
Department of Surgery, Diakonieklinikum Alten Eichen (Dr. Dörner)
Department of Hepatobiliary Surgery, University Hospi tal Hamburg (PI: Dr. Nashan)
Cancer -relevant Proteins Gene Expression Profiling
Cancer Normal
Impact of Anesthesia and Surgery on Gene and Protein Exp ression in Colon and Liver Tissue : Study Design
Cancer -relevant Proteins
Protein Quantification Cellular Distribution
Identification of Surgery Dependent Molecules
pMEK1/2
0
1000
2000
3000
4000
5000
MS
D s
igna
l [U
]
Gene Expression Profiling
Specific Genes Comprehensive Analysis
Analysis of Proteins:MSD and Immunohistochemistry
Frozen Tissue:MSD analysis
FFPE TissueIHC (Ventana)
• pEGFR/total EGFR
•pMEK1/2/total MEK1/2 (Ser217/221)
• pEGF-R
• pHER-3•pMEK1/2/total MEK1/2 (Ser217/221)
• pERK1/2/total ERK1/2 (Thr202/Tyr204, Thr185/Tyr187)
• pAkt/total Akt (Ser473)
• pmTOR/total mTOR (Ser 2448)
•pP70S6K/total P70S6K (Thr421/Ser424)
• pGSK-3beta/total GSK-3beta (Ser9)
• control protein x
• Hif-1alpha
• pHER-3
• pMAPK
• pAKT
• pmTOR
Impact of Anesthesia and Surgery on Gene and Protein Exp ression in Colorectal Tissue (Project 2)
Colon Tissue
Normal Cancer
Start of
Blood
Normal
Collected:50 / 40
Surgery
Post-Surgery
10 min
20 min
45 min
BeforeAnesthesia
Before skinincision
3
HSP27-normal3
HSP27-tumor
Impact of intra- and postsurgical factors:Analysis of Total-control protein X by MSD (Cellular Str ess Marker)
Normal Normal
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
1
2
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
1
2
pre resection 10 min post resection 20 min post resection 45 min post resectionre
lativ
e ch
ange
time
35
HSP27-normalphosphorylation
30
35
HSP27-tumorphosphorylation
Impact of intra- and postsurgical factors:Analysis of Phospho-control protein X by MSD (Cellular S tress Marker)
Normal Tumor
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
5
10
15
20
25
30
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
5
10
15
20
25
30
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
P-protein
Analysis of HER-family Pathway in CRC Tissue:Impact of intra- and postsurgical factors
P-protein
P-protein
4
5
EGFR-normal
4
5
EGFR-tumor
Impact of intra- and postsurgical factors:Analysis of Total-EGFR by MSD
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
1
2
3
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
1
2
3
pre resection 10 min post resection 20 min post resection 45 min post resectionre
lativ
e ch
ange
time
16
18
20
EGFR-normalphosphorylation
16
18
20
EGFR-tumorphosphorylation
Impact of intra- and postsurgical factors:Analysis of Phospho-EGFR by MSD
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
2
4
6
8
10
12
14
16
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
2
4
6
8
10
12
14
16
pre resection 10 min post resection 20 min post resection 45 min post resectionre
lativ
e ch
ange
time
EGFR-%Phospho-normalpe
rcen
tage
0
20
40
60
80
100
EGFR-%Phospho-tumor
perc
enta
ge
0
20
40
60
80
100
Impact of intra- and postsurgical factors:Analysis of Phospho/Total-EGFR by MSD
pre r
esec
tion
10 m
in po
st re
secti
on20
min
post
rese
ction
45 m
in po
st re
secti
on
0
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
EGFR-%Phospho-normal
0.4648
Gaussian Approximation
ns
No
4
2.559
Difference in rank sum
16.04
6.363
8.900
-9.675
-7.138
2.538
Significant? P < 0.05?
No
No
No
No
No
No
Summary
ns
ns
ns
ns
ns
ns
pre re
secti
on
10 m
in p os
t res
ectio
n
20 m
in p ost
r ese
ction
45 m
in p ost
rese
ction
0
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
EGFR-%Phospho-tumor
0.4629
Gaussian Approximation
ns
No
4
2.569
Difference in rank sum
-12.15
-14.29
-4.163
-2.138
7.988
10.13
Significant? P < 0.05?
No
No
No
No
No
No
Summary
ns
ns
ns
ns
ns
ns
pEGFR normalH
-sco
re
pre re
secti
on
10 min
post
rese
ction
20 min
pos t r
ese cti
on
45 min
post
rese
ction
0
50
100
150
pEGFR tumor
H-s
core
pre r
esec
tion
10 m
in po
s t res
ection
20 m
in po
st re
secti
on
45 m
in po
s t res
ection
0
50
100
150
200
Analysis of Phospho-EGFR by IHC
pre re
secti
on
10 min
post
rese
ction
20 min
pos t r
ese cti
on
45 min
post
rese
ction
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
pEGFR normal
0.0268
Gaussian Approximation
*
Yes
4
9.194
Difference in rank sum
16.45
16.45
20.400.0
3.950
3.950
Significant? P < 0.05?
No
No
YesNo
No
No
Summary
ns
ns
*ns
ns
ns
pre r
esec
tion
10 m
in po
s t res
ection
20 m
in po
st re
secti
on
45 m
in po
s t res
ection
Table Analyzed
Kruskal-Wallis test
P valueExact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection20 min post resection vs 45 min post resection
pEGFR tumor
0.0020Gaussian Approximation
**
Yes
4
14.80
Difference in rank sum
22.53
20.58
25.10
-1.950
2.5754.525
Significant? P < 0.05?
Yes
Yes
Yes
No
NoNo
Summary
*
*
**
ns
nsns
pHer3 normal
H-s
core
pre re
secti
o n
10 m
in pos t r
esecti
on
20 m
in po
st res
ectio
n
45 m
in pos
t rese
ction
0
50
100
150
pHer3 tumor
H-s
core
pre
resec
tion
10 m
in po
st re
sect
ion
20 m
in pos
t res
ectio
n
45 m
in p
ost r
esec
tion
0
50
100
150
Analysis of Phospho-HER3 by IHC
Table Analyzed
One-way analysis of variance
P value
P value summary
Are means signif. different? (P < 0.05)
Number of groups
F
R square
Bartlett's test for equal variances
Bartlett's statistic (corrected)
P value
P value summary
Do the variances differ signif. (P < 0.05)
ANOVA Table
Treatment (between columns)
Residual (within columns)
Total
Bonferroni's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
pHer3 normal
0.1131
ns
No
4
2.056
0.07508
2.045
0.5631
ns
No
SS
2550
31415
33965
Mean Diff.
6.550
10.10
15.55
3.550
9.000
5.450
df
3
76
79
t
1.019
1.571
2.419
0.5522
1.400
0.8477
MS
850.0
413.4
Significant? P < 0.05?
No
No
No
No
No
No
Summary
ns
ns
ns
ns
ns
ns
95% CI of diff
-10.87 to 23.97
-7.317 to 27.52
-1.867 to 32.97
-13.87 to 20.97
-8.417 to 26.42
-11.97 to 22.87
10 m
in po
st re
sect
ion
20 m
in pos
t res
ectio
n
45 m
in p
ost r
esec
tion
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
pHer3 tumor
0.0187
Gaussian Approximation
*
Yes
4
9.990
Difference in rank sum
17.75
13.73
21.03
-4.025
3.275
7.300
Significant? P < 0.05?
No
No
Yes
No
No
No
Summary
ns
ns
*
ns
ns
ns
P-protein
Analysis of HER-family Pathway in CRC Tissue:Impact of intra- and postsurgical factors
P-protein
120
140
160
Akt-normal
120
140
160
Akt-tumor
Impact of intra- and postsurgical factors:Analysis of Total-AKT by MSD
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
20
40
60
80
100
120
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
20
40
60
80
100
120
pre resection 10 min post resection 20 min post resection 45 min post resectionre
lativ
e ch
ange
time
4
Akt-normalphosphorylation
4
Akt-tumorphosphorylation
Impact of intra- and postsurgical factors:Analysis of Phospho-AKT by MSD
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
1
2
3
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
1
2
3
pre resection 10 min post resection 20 min post resection 45 min post resectionre
lativ
e ch
ange
time
Akt-%Phospho-normal
perc
enta
ge
0
20
40
60
80
100
Akt-%Phospho-tumor
perc
enta
ge
0
20
40
60
80
100
Impact of intra- and postsurgical factors:Analysis of Phospho/Total-AKT by MSD
pre re
secti
on
10 m
in p os
t res
ectio
n
20 m
in p ost
rese
ction
45 m
in po
st re
secti
on
0
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
Akt-%Phospho-normal
< 0.0001
Gaussian Approximation
****
Yes
4
54.76
Difference in rank sum
53.74
61.75
68.26
8.013
14.53
6.513
Significant? P < 0.05?
Yes
Yes
Yes
No
No
No
Summary
***
***
***
ns
ns
ns
pre re
secti
on
10 m
in p os
t res
ectio
n
20 m
in p ost
r ese
ction
45 m
in p ost
rese
ction
0
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
Akt-%Phospho-tumor
< 0.0001
Gaussian Approximation
****
Yes
4
80.39
Difference in rank sum
82.64
71.80
67.11
-10.84
-15.53
-4.688
Significant? P < 0.05?
Yes
Yes
Yes
No
No
No
Summary
***
***
***
ns
ns
ns
pAkt normal
H-s
core
pre re
secti
on
10 m
in p
ost re
secti
on
20 m
in p ost
rese
ction
45 min
post
r esec
tion
0
50
100
150
pAkt tumor
H-s
core
pre
res ec
tion
10 m
in po
st re
secti
on
20 m
in po
st re
secti
on45
min
pos
t res
ectio
n
0
50
100
150
200
250
Analysis of Phospho-AKT by IHC
10 m
in p
ost re
secti
on
20 m
in p ost
rese
ction
45 min
post
r esec
tion
Table Analyzed
One-way analysis of variance
P value
P value summary
Are means signif. different? (P < 0.05)
Number of groups
F
R square
Bartlett's test for equal variances
Bartlett's statistic (corrected)
P value
P value summary
Do the variances differ signif. (P < 0.05)
ANOVA Table
Treatment (between columns)
Residual (within columns)
Total
Bonferroni's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
pAkt normal
0.6336
ns
No
4
0.5745
0.02217
4.075
0.2534
ns
No
SS
641.2
28279
28920
Mean Diff.
5.750
4.600
7.700
-1.150
1.950
3.100
df
3
76
79
t
0.9426
0.7541
1.262
0.1885
0.3197
0.5082
MS
213.7
372.1
Significant? P < 0.05?
No
No
No
No
No
No
Summary
ns
ns
ns
ns
ns
ns
95% CI of diff
-10.78 to 22.28
-11.93 to 21.13
-8.825 to 24.23
-17.68 to 15.38
-14.58 to 18.48
-13.43 to 19.63
10 m
in po
st re
secti
on
20 m
in po
st re
secti
on45
min
pos
t res
ectio
n
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
pAkt tumor
0.0010
Gaussian Approximation
**
Yes
4
16.21
Difference in rank sum
16.63
17.98
29.30
1.350
12.68
11.33
Significant? P < 0.05?
No
No
Yes
No
No
No
Summary
ns
ns
***
ns
ns
ns
18
20
mTOR-normal
18
20
mTOR-tumor
Impact of intra- and postsurgical factors:Analysis of Total-mTOR by MSD
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
2
4
6
8
10
12
14
16
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
2
4
6
8
10
12
14
16
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
2
mTOR-normalphosphorylation
2
mTOR-tumorphosphorylation
Impact of intra- and postsurgical factors:Analysis of Phospho-mTOR by MSD
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
1
1
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
1
1
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
mTOR-%Phospho-normalpe
rcen
tage
50
60
70
80
90
100
mTOR-%Phospho-tumor
perc
enta
ge
50
60
70
80
90
100
Impact of intra- and postsurgical factors:Analysis of Phospho/Total-mTOR by MSD
pre r
esec
tion
10 m
in po
st re
secti
o n
20 m
in po
st re
secti
on
45 m
in po
st re
secti
on
50
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
mTOR-%Phospho-normal
0.5191
Gaussian Approximation
ns
No
4
2.266
Difference in rank sum
11.78
7.588
-1.663
-4.188
-13.44
-9.250
Significant? P < 0.05?
No
No
No
No
No
No
Summary
ns
ns
ns
ns
ns
ns
pre r
ese ct
ion
10 m
in po
st re
sec
tion
20 m
in po
st re
sectio
n
45 m
in po
st re
sec tio
n
50
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
mTOR-%Phospho-tumor
< 0.0001
Gaussian Approximation
****
Yes
4
31.84
Difference in rank sum
43.81
54.80
38.54
10.99
-5.275
-16.26
Significant? P < 0.05?
Yes
Yes
Yes
No
No
No
Summary
***
***
**
ns
ns
ns
pmTOR tumor
H-s
core
0
100
200
300
pmTOR normal
H-s
core
0
50
100
150
200
Analysis of Phospho-mTOR by IHC
pre re
secti
on
10 m
in po
st re
secti
on
20 m
in po
st re
secti
on
45 m
in po
st re
secti
on
0
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resectionpre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
pmTOR tumor
0.5953
Gaussian Approximationns
No
4
1.891
Difference in rank sum
-7.250
-4.975-9.675
2.275
-2.425
-4.700
Significant? P < 0.05?
No
NoNo
No
No
No
Summary
ns
nsns
ns
ns
ns
pre re
sec tio
n
10 m
in po
st re
secti
on20
min
post re
secti
on
45 m
in po
s t res
ectio
n
0
Table Analyzed
Kruskal-Wallis testP value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groupsKruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resectionpre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection20 min post resection vs 45 min post resection
pmTOR normal
0.0026
Gaussian Approximation
**
Yes
414.21
Difference in rank sum
-6.100-10.80
-26.40
-4.700
-20.30-15.60
Significant? P < 0.05?
NoNo
Yes
No
YesNo
Summary
nsns
**
ns
*ns
100
120
p70s6k-normal
100
120
p70s6k-tumor
Impact of intra- and postsurgical factors:Analysis of p70s6k by MSD
0
20
40
60
80
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
20
40
60
80
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
3
4
p70s6k-normalphosphorylation
3
4
p70s6k-tumorphosphorylation
Impact of intra- and postsurgical factors:Analysis of Phospho-p70s6k by MSD
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
1
2
3
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
1
2
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
getime
p70s6K-%Phospho-normal
perc
enta
ge
0
20
40
60
80
100
p70s6K-%Phospho-tumor
perc
enta
ge
0
20
40
60
80
100
Impact of intra- and postsurgical factors:Analysis of Phospho/Total-p70s6k by MSD
pre re
secti
on
10 m
in po
st re
secti
on
20 m
in po
st r es
ectio
n
45 m
in po
st r es
ectio
n
0
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
p70s6K-%Phospho-normal
0.0188
Gaussian Approximation
*
Yes
4
9.969
Difference in rank sum
24.31
5.488
-6.750
-18.83
-31.06
-12.24
Significant? P < 0.05?
No
No
No
No
Yes
No
Summary
ns
ns
ns
ns
*
ns
pre r
ese cti
on
10 m
in po
st re
sectio
n
20 m
in po
st re
sectio
n
45 m
in po
st r e
secti
on
0
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
p70s6K-%Phospho-tumor
< 0.0001
Gaussian Approximation
****
Yes
4
50.80
Difference in rank sum
69.29
40.74
16.88
-28.55
-52.41
-23.86
Significant? P < 0.05?
Yes
Yes
No
Yes
Yes
No
Summary
***
***
ns
*
***
ns
20
25
GSK3beta-normal
20
25
GSK3beta-tumor
Impact of intra- and postsurgical factors:Analysis of Total-GSK3beta by MSD
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
5
10
15
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
5
10
15
pre resection 10 min post resection 20 min post resection 45 min post resectionre
lativ
e ch
ange
time
3
GSK3beta-normalphosphorylation
3
GSK3beta-tumorphosphorylation
Impact of intra- and postsurgical factors:Analysis of Phospho-GSK3beta by MSD
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
1
2
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
1
2
pre resection 10 min post resection 20 min post resection 45 min post resectionre
lativ
e ch
ange
time
GSK3beta-%Phospho-normalpe
rcen
tage
0
20
40
60
80
100
GSK3beta-%Phospho-tumor
perc
enta
ge
0
20
40
60
80
100
Impact of intra- and postsurgical factors:Analysis of Phospho/Total-GSK3beta by MSD
pre r
e sect
ion
10 m
in pos
t res
ectio
n
20 m
in po
st re
secti
on45
min
pos
t rese
ction
0
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
GSK3beta-%Phospho-normal
0.0123
Gaussian Approximation
*
Yes
4
10.89
Difference in rank sum
14.39
18.84
33.88
4.450
19.49
15.04
Significant? P < 0.05?
No
No
Yes
No
No
No
Summary
ns
ns
**
ns
ns
ns
pre re
secti
on
10 m
in pos
t re se
ctio
n
20 m
in po
st re
sect
ion
45 m
in po
st re
sec
tion
0
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
GSK3beta-%Phospho-tumor
< 0.0001
Gaussian Approximation
****
Yes
4
44.38
Difference in rank sum
64.91
51.25
45.79
-13.66
-19.13
-5.463
Significant? P < 0.05?
Yes
Yes
Yes
No
No
No
Summary
***
***
***
ns
ns
ns
P-protein
Analysis of HER-family Pathway in CRC Tissue:Impact of intra- and postsurgical factors
P-protein
P-protein
10
12
MEK-normal
10
12
MEK-tumor
Impact of intra- and postsurgical factors:Analysis of Total-MEK by MSD
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
2
4
6
8
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
2
4
6
8
pre resection 10 min post resection 20 min post resection 45 min post resectionre
lativ
e ch
ange
time
7
MEK-normalphosphorylation
6
7
MEK-tumorphosphorylation
Impact of intra- and postsurgical factors:Analysis of Phospho-MEK by MSD
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
1
2
3
4
5
6
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
1
2
3
4
5
6
pre resection 10 min post resection 20 min post resection 45 min post resectionre
lativ
e ch
ange
time
MEK-%Phospho-normalpe
rcen
tage
0
20
40
60
80
100
MEK-%Phospho-tumor
perc
enta
ge
0
20
40
60
80
100
Impact of intra- and postsurgical factors:Analysis of Phospho/Total-MEK by MSD
pre re
secti
on
10 m
in p os
t res
ectio
n
20 m
in p ost
r ese
ction
45 m
in p ost
rese
ction
0
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
MEK-%Phospho-normal
< 0.0001
Gaussian Approximation
****
Yes
4
27.13
Difference in rank sum
52.61
17.30
19.04
-35.31
-33.58
1.738
Significant? P < 0.05?
Yes
No
No
Yes
Yes
No
Summary
***
ns
ns
**
**
ns
pre re
secti
on
10 m
in p os
t res
ectio
n
20 m
in p ost
r ese
ction
45 m
in p ost
rese
ction
0
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
MEK-%Phospho-tumor
< 0.0001
Gaussian Approximation
****
Yes
4
27.93
Difference in rank sum
52.68
38.94
32.39
-13.74
-20.29
-6.550
Significant? P < 0.05?
Yes
Yes
Yes
No
No
No
Summary
***
**
*
ns
ns
ns
7
8
ERK-normal
7
8
ERK-tumor
Impact of intra- and postsurgical factors:Analysis of Total-ERK (MAPK) by MSD
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
1
2
3
4
5
6
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
1
2
3
4
5
6
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
6
7
ERK-normalphosphorylation
6
7
ERK-tumorphosphorylation
Impact of intra- and postsurgical factors:Analysis of Phospho-ERK (pMAPK) by MSD
Case NC7 Case NC13 Case NC17 Case NC27 Case NC35 Case NC39 Case NC40 Case NC41 Case NC42 Case NC47
Case NC9 Case NC11 Case NC12 Case NC18 Case NC20 Case NC21 Case NC28 Case NC30 Case NC33 Case NC36
Case NC2 Case NC3 Case NC4 Case NC5 Case NC8 Case NC10 Case NC15 Case NC16 Case NC22 Case NC23
Case NC25 Case NC26 Case NC29 Case NC32 Case NC34 Case NC37 Case NC38 Case NC43 Case NC46 Case NC48
0
1
2
3
4
5
6
pre resection 10 min post resection 20 min post resection 45 min post resection
rela
tive
chan
ge
time
0
1
2
3
4
5
6
pre resection 10 min post resection 20 min post resection 45 min post resectionre
lativ
e ch
ange
time
ERK-%Phospho-normal
perc
enta
ge
0
20
40
60
80
100
ERK-%Phospho-tumor
perc
enta
ge
0
20
40
60
80
100
Impact of intra- and postsurgical factors:Analysis of Phospho/Total-ERK (pMAPK) by MSD
pre re
secti
on
10 m
in p os
t res
ectio
n
20 m
in p ost
r ese
ction
45 m
in p ost
rese
ction
0
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
ERK-%Phospho-normal
0.0002
Gaussian Approximation
***
Yes
4
19.30
Difference in rank sum
44.76
17.23
16.41
-27.54
-28.35
-0.8125
Significant? P < 0.05?
Yes
No
No
Yes
Yes
No
Summary
***
ns
ns
*
*
ns
pre re
secti
on
10 m
in p os
t res
ectio
n
20 m
in p ost
r ese
ction
45 m
in p ost
rese
ction
0
Table Analyzed
Kruskal-Wallis test
P value
Exact or approximate P value?
P value summary
Do the medians vary signif. (P < 0.05)
Number of groups
Kruskal-Wallis statistic
Dunn's Multiple Comparison Test
pre resection vs 10 min post resection
pre resection vs 20 min post resection
pre resection vs 45 min post resection
10 min post resection vs 20 min post resection
10 min post resection vs 45 min post resection
20 min post resection vs 45 min post resection
ERK-%Phospho-tumor
< 0.0001
Gaussian Approximation
****
Yes
4
42.23
Difference in rank sum
63.91
49.81
37.58
-14.10
-26.34
-12.24
Significant? P < 0.05?
Yes
Yes
Yes
No
No
No
Summary
***
***
**
ns
ns
ns
Liver
Normal Met‘s
ArteryClamping
Impact of Anesthesia and Surgery on Gene and Protein Exp ression in Liver Tissue (Project 1)
Blood
Normal
Collected:42 / 40 (still continued)
Clamping
0min
10 min
Post-Surgery
10 min
20 min
45 min
BeforeAnesthesia
Before skinincision
Cancer-relevant Proteins Gene Expression Profiling
Cancer Normal
Impact of Anesthesia and Surgery on Gene and Protein Exp ression in Colon and Liver Tissue : Next Steps
Protein Quantification Cellular Distribution
pMEK1/2
0
1000
2000
3000
4000
5000
MS
D s
igna
l [U
]
Specific Genes Comprehensive Analysis
Colon:Completed
Liver:First set of 20 completedFinal set of 20 shortly
Colon:Completed by end of March
Liver:Completed shortly
Summary
• Positive control markers demonstrate that cold ischemia a s well as surgery can
have a significant impact on expression and activity of fu nctional proteins
• Cancer and corresponding normal tissue react different ( normal<cancer)
• High variability of functional protein expression and eff ects of intra- and
postsurgery between patients
• Overall, MSD data and IHC analyses are constistent altho ugh in some markers
(e.g., p-mTOR) differences can be seen
• A comprehensive data analysis – including gene expression data – will follow when
results of the liver study are completed. This will includ e correlative analysis of
clinical and anesthesiological data
Thank you very much for your attention!
Greetings from Hamburg
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