Transcript New Options of Cancer Detection by an EPR/ESR Biomarker Test

New Options of Cancer
Detection by an EPR/ESR
Biomarker Test
Gert A. Matthes
MedInnovation GmbH, Berlin, Germany
II Russian Congress of Laboratory Medicine, Moscow, October 12-14
Section: Fundamental Questions of Clinical and Laboratory Medicine
New Options of Cancer Detection by EPR/ESR Biomarker Test
o Basis of the test procedure




Cancer specific albumin conformation changes
Principle of the EPR/ESR biomarker test
Recent Advances in EPR/ESR test analysis (DR, RTQ, BE, DTE, DRN)
Results for several cancer types
o Early detection of cancer
 Look-back samples as test specimens
 Backward directed cancer detection – from diagnosis to a possible beginning
 Very early cancer diagnosis by EPR/ESR
o Identification of the cancer localization
 New Calculation Procedure for Cancer Detection & Localization
 Matching EPR/ESR spectra search for cancer detection (resp. other diseases or
healthy person)
 Cancer localization by EPR/ESR
 EPR/ESR Results – Printout of the Data Sheet
o Therapy monitoring and follow up
 Case reports on therapy monitoring
 Case report on follow up and relapse control
o Conclusions
Objective
• Albumin conformational changes can be
caused by direct and or indirect binding
due to an accumulation of cancer
induced ligands (on albumin bound or
accumulated low molecular weight
molecules) which interfere the binding
characteristics of albumin.
• These changes of albumin conformation flexibility and binding
characteristics are determined by electron paramagnetic resonance (EPR)/electron spin resonance (ESR) spectroscopy.
• The objective is an analysis of cancer patients concerning serum
albumin binding & dissociation function by the EPR/ESR method.
• Changes in albumin were detected in patient samples, and their
utility for screening, diagnosis and therapy monitoring of cancer
evaluated.
EPR/ESR Albumin Analysis for Cancer Diagnostics?
1. Serum albumin is in permanent exchange with cells and tissues
2. Serum albumin is the main carrier of all circulating biomarkers




for
for
for
for
cancer risks
interactions between tumor and tissues
tumor growth
functional related tumor marker
3. Changes of albumin conformation can be caused by direct and/or
indirect influences/ligand binding
4. Serum albumin is significantly longer kept in cancer tissue. Cancer
cells produce a subset of type/stage specific bioactive molecules
that bind to albumin. Its accumulation should lead to allosteric
changes in albumin conformation flexibility.
EPR/ESR Albumin Analysis for Cancer Diagnostics?
1. Serum albumin is in permanent exchange with cells and tissues
2. Serum albumin is the main carrier of all circulating biomarkers




for
for
for
for
cancer risks
interactions between tumor and tissues
tumor growth
functional related tumor marker
3. Changes of albumin conformation can be caused by direct and/or
indirect influences/ligand binding
4. Serum albumin is significantly longer kept in cancer tissue. Cancer
cells produce a subset of type/stage specific bioactive molecules
that bind to albumin. Its accumulation should lead to allosteric
changes in albumin conformation flexibility.
 Malignant processes change albumin conformation and
cause disturbances of fatty acid transport
 In active malignant situations tumor associated albumin
changes of fatty acid transport are reliable assessed by
EPR/ESR spectroscopy
EPR/ESR Test Principle
The novel biomarker test uses EPR/ESR spectrometer ESPIRE-100 (MedInnovation GmbH,
Berlin, Germany) to estimate the functionality of albumin in serum.
It is based on a comparison of three different serum albumin solutions after 10 min
incubation of 50 µl serum aliquots with increasing concentrations of a spin labelled fatty
acid (16-DSA, 0.8–2.3 mM) and ethanol (1.9–3.8 M), which simulate binding, transport and
release conditions in vitro.
EPR/ESR equipment has been achieved the “CE Marking” (European Conformity, according EU 93/42/EEC medical devices directive) for medical products. The EPR/ESR tumor
marker test is “CE marked” (German Institute for Medical Documentation and Information
(DIMDI), Cologne, Germany), approved for in vitro clinical diagnostics (IVD) of cancer, and
registered at the DIMDI as "Other tumor markers".
Recent Advances in EPR/ESR Technology
 Discrimination function/Diagnostic Result DR
From the cancer modified albumin binding characteristic the integral discrimination function DR is calculated. DR gives a statement about the probability an active malignant disease (DR<1.0: an active
malignant disease exists or emerges with a high probability; DR>1.0: one is healthy; between DR>1.0
to <1.2: one has no cancer, probably no cancer). In case of DR value in the threshold range one have
to decide whether there is an influence of an inflammation or medication.
Recent Advances in EPR/ESR Technology
 Discrimination function/Diagnostic Result DR
From the cancer modified albumin binding characteristic the integral discrimination function DR is cal-culated. DR gives a
statement about the probability an active malignant disease (DR<1.0: an active malignant disease exists or emerges
with a high probability; DR>1.0: one is healthy; between DR>1.0 to <1.2: one has no cancer, probably no cancer). In
case of DR value in the threshold range one have to decide whether there is an influence of an inflammation or
medication.
 Albumin transport parameter RTQ, BE, DTE
The albumin transport functionality test delivers an evidence of detoxification, binding and transport
capacity for patients with liver diseases and Sepsis/SIRS, and may have an impact on diagnosis and
prognosis of such severe diseases. The calculated values are albumin transport parameter RTQ – real
transport quality (global parameter of albumin transport function), BE – binding efficiency
(physicochemical property of fatty acid binding sites), DTE – detoxification efficiency (albumin as a
transport molecule in a competitive situation).
Recent Advances in EPR/ESR Technology
 Discrimination function/Diagnostic Result DR
From the cancer modified albumin binding characteristic the integral discrimination function DR is cal-culated. DR gives a
statement about the probability an active malignant disease (DR<1.0: an active malignant disease exists or emerges
with a high probability; DR>1.0: one is healthy; between DR>1.0 to <1.2: one has no cancer, probably no cancer). In
case of DR value in the threshold range one have to decide whether there is an influence of an inflammation or
medication.
 Albumin transport parameter RTQ, BE, DTE
The albumin transport functionality test delivers an evidence of detoxification, binding and transport capacity for
patients with liver diseases and Sepsis/SIRS, and may have an impact on diagnosis and prognosis of such severe
diseases. The calculated values are albumin transport parameter RTQ – real transport quality (global parameter of
albumin transport function), BE – binding efficiency (physicochemical property of fatty acid binding sites), DTE –
detoxification efficiency (albumin as a transport molecule in a competitive situation).
 Introduction of the new discrimination function DRN
A sensitivity analysis of the integral discriminator DR resulted in the new discrimination factor DRN. This
factor DRN allows more accurate separation between cancer patients, the chronically ill and healthy
persons (DRN <0: carcinoma; DRN between> 0 and <2: no cancer, but not healthy; DRN > 2: healthy).
Thus existing problems in the interpretation of the old DR can be largely reduced or excluded:
Cancer
Healthy
Colon Ca
Inflam-
Colitis
(mean)
(mean)
metast.
mation
ulcer.
Dialysis
Ovar Ca
Pancrea-
Hashi-
Preg-
therapy
tis, chron.
moto
nancy
DR
-0,617
5,103
-2,187
-0,415
2,511
-0,427
0,837
5,423
0,544
0,123
DR
cancer
healthy
cancer
cancer
healthy
cancer
cancer
healthy
cancer
cancer
DRN
-1,279
5,951
-15,224
0,326
3,677
0,395
3,205
6,484
2,297
2,298
DRN
cancer healthy
cancer no canc. healthy no canc. healthy
not healthy
not healthy
healthy healthy healthy
Results of EPR/ESR cancer analysis
1.021 samples
Cut off: DR<1.0 cancer positive
• 479 cancer
patients
• 428 healthy
subjects
• 114 chronic
diseases
Healthy – Cancer
Sensitivity 92.7%
Specificity 94.9%
Cancer – Chronic
Sensitivity 92.5%
Specificity 68.4%
Results of EPR/ESR Cancer Analysis
Most common cancer types – Diagnostic Sensivity
Tumor marker
(data from literature)
EPR/ESR (MedInnovation)
Prostate cancer
Breast cancer
(PSA, fPSA, (fPSA/tPSA)
24-71%
(CEA, CA 15-3, AFP, CA 19-9, CA 72-4, CA 125)
28-79%
Colon cancer
90%
(NSE, SCC, CYFRA 21-1, CEA, AFP)
100%
24-78%
(NSE, SCC, CYFRA 21-1, CEA, AFP)
24-66%
Cervical cancer
(CYFRA 21-1, TPA)
(SCC, CEA)
100%
88%
Lung cancer
Bladder cancer
24-58%
48-90%
(CEA, AFP, CA 19-9)
Lung cancer
10-71%
19-91%
Colon cancer
(CEA, AFP, CA 19-9)
20-43%
Tumor marker (literature)
EPR/ESR (MedInnovation)
24-69%
Source: L. Thomas: Labor und Diagnose: Indikation und Bewertung von Laborbefunden für die medizinische Diagnostik. TH-Books, Frankfurt/Main, 2012; MedInnovation GmbH, Berlin, Germany, 2016..
100%
100%
Early Detection of Cancer
Look-back samples of blood donors must taken at each blood donation (and
stored for at least 2 years at <-20 °C), because there may be a risk of infection
from a donor to a recipient.
For the EPR/EPR studies such samples were used. There are several look-back
samples of some blood donors if they has repeatedly donated whole blood or
blood components as permanent blood donors. Approximately 1 from 10.000
donors reports a cancer/tumor post blood donation.
Aim of the retrospective sample examination on ESR/EPR tumor marker was to
find out the maximum time period between recognition of a tumor in samples
and clinical cancer diagnosis.
Clinical Diagnosis
(conventional methods)
Look-back Samples as Test Specimens
•
•
60 look back samples (stored between 1 to 23 months at <-20 °C) from 16 blood
donors with a post donation report on cancer were tested retrospectively.
Cancer: breast, prostate, kidney, stomach, colon, rectum, bladder, lung,
skin, testicular, hypophysis/pituitary gland cancer, lymphoma.
•
By EPR/ESR all 16 donors were tested cancer positive in each of the lookback sample 1 to 21 months before cancer detection (16/16) - by other
tumor marker only 7/16 (CEA, AFP, CA 19-9, CA 125, CA 15-3, CA 72-4, NSE, PSA, HCG,
S-100, CYFRA 21-1, TSH, LDH, LTH, ACTH).
•
A hitherto undetected malignant growth process (active or inactive) can be
seen in look-back samples up to two years before the clinical cancer diagnosis.
•
An ESR/EPR screening of blood donors is contributing either to donor
safety (earliest possible cancer detection) or transfusion safety (there is
little evidence for a transmission of cancer by transfusion - the scientific
question is still unresolved)
Backward Directed Cancer Detection
- from cancer diagnosis to a possible beginning
Look-back samples of a blood donor (man,
-
51 years) who
developed a pituitary gland cancer later:
• EPR/ESR test DR was positive from month 18 to month 1 before
cancer diagnosis
• Prolactin was positive from month 18 to month 1 before cancer
diagnosis
• Others tumor marker TSH, LH, FSH, and ACTH were negative
from month 15 to month 1 before cancer diagnosis
Cancer specific modifications albumin functionality could be detected by EPR/ESR between 1 to 18 months before the tumor was
detected by other means.
Look-back samples of a blood donor (woman, 52 years)
who developed a breast cancer later:
•
•
•
EPR/ESR test DR was positive from month 15 to month 0.9
before cancer diagnosis
Others tumor marker CA-19, CA125, CA15-3, Ca 72-4, CYFRA 21-1 were negative from month 15 to month 0.9 before
cancer diagnosis
Cancer specific modifications albumin functionality could be
detected by EPR/ESR between 0.9 to 15 months before the
tumor was detected by other means.
Very Early Cancer Diagnosis by EPR/ESR
•
Look-back samples (LBS) from blood donors (who were tested at the time of blood donation as healthy and later developed a cancer) are well suited to identify the earliest time of
occurrence of cancer.
•
There are time periods (3–5 months) of active and silent tumor activity (in prostate, kidney, breast, and bladder cancer).
•
In all probes recognizable changes of serum albumin from 0.2 up to 30 months before the
clinical diagnosis of malignancy could be detected.
Time between EPR/ESR cancer diagnosis in look back samples and clinical
diagnosis for several cancer types
Cancer types
EPR/ESR detection
before clinical diagnosis
Tumor marker detection
before clinical diagnosis
CEA: 32-2.0 mo., CA 72-4: 17-2 mo.
CA 19-9: , CA 15-3: , CYFRA 21-1: 
CEA: , CA 19-9: 
CEA: , NSE: 
PSA: 24-5.0
NSE: 17-1.0
Prolactin: 46-1.0 mo., TSH: , FSH: 
CYFRA: 
•
Breast
34-0.9 months (mo.)
•
•
•
•
•
•
Colon
Kidney
Prostate
Lung
Pituitary
Bladder
31-0.2
36-12
36-5.0
17-1.0
46-1.0
16-1.0
mo.
mo.
mo.
mo.
mo.
mo.
DR value in LBS of Donors with post-donation report on cancer
Fig. A: Time-dependent DR values in all lookback samples (LBS, n=110) of donors
(n=56) with post-donation reports on cancer.
Fig. A
1
DR value (cancer positive if DR<1.0)
DR (Mean)
0,8
Linear (DR (Mean))
0,6
Fig. B: Analysis of look-back samples of a
blood donor with a post-donation report on
colon cancer.
0,4
0,2
Fig. C: Analysis of look-back samples of a
blood donor with a post-donation report on
prostate cancer.
0
0 to 6
7 to 9
10 to 12
13 to 18
19 to 24
25 to 30
31 to 36
-0,2
Month before Cancer Diagnosis
DR value (cancer positive if DR<1.0)
1,5
Fig. B
1
0,45
0,5
0
-0,5
10
13
-0,30
-0,37
18
-0,20
20
-1
Prostate Cancer (64 years, male)
1,91
28
2,5
DR value (cancer positive if DR<1.0)
Colon Cancer (61 years, male)
2
2,13
2
1,5
1,29
1
0,62
0,5
0
2
-0,5
Months before Cancer Diagnosis
Fig. C
-0,24
6
14
Months before Cancer Diagnosis
18
Identification of the Cancer Localization
In the absence of tumor specificity, and especially organ specificity, most tumor markers
are of little importance in supporting the diagnosis, especially in case of an unknown
location of a possible tumor.
Therefore, special attention was given to the question of whether and to what effect the
cancer type (entity) can be determined from the EPR/ESR spectra.
The measured spectra show
marked differences.
The spectra (each spectrum
has 4.096 interpolation
points) were checked for
differences, and then a
match analysis for comparison of the sample spectra
with all spectra in the pool
was applied.
There is a legitimate hope
that an exact recognition will
be obtained if sufficient reference spectra of different
individuals (healthy group,
chronically ill group, cancer
group) are available.
New Calculation Procedure for Cancer
New Calculation Procedure for Cancer Detection & Localisation of a Tumor
Detection & Localization
Blood sampling
Laboratory
Patient
serum
sample
EPR/ESR
Test
* dilution
* mixing
EPR/ESR spectra recording
and spectra analysis
Spectra A, B, C MMS System
D, E, F, G, H Calculation of
Discrimant factor
* incubation
Steps to the final diagnosis
1. Step
MMS System (DR)
Result
First
* DR, D-DR
Interpretation
MMS System MMS System
DR calculation
>1.0
1-1.2
RTQ, BE, DTE
<1.0
3. Step
Both Systems
Final
Interpretation Interpretation
Biophysical parameter
DR >1,0
DRN >2.0
* BE, RTE, DTE
DR 1-1.2
DR <1,0
DRN 0-2
Differential
DRN <0.0
Diagnosis
A, B, C spectrum matches one or more
Spectra A, B, C LOC Program
D, E, F, G, H Search of an appropriate
spectrum in the LOC
spectra pool for the patient's Cancer
serum on the basis of a
confirmed
preset spectra analysis.
Cancer
not
confirmed
EPR/ESR
Recording
Patient
serum /
plasma
2. Step
New System (DRN/LOC)
Result
Second
DR Confirmation
by calculation of DRN
DRN >2.0
DRN 0-2
DRN <0.0
and / or
within the existing LOC pool spectra.
1. choice
Cancer X
2. choice
Cancer Y
Cancer
3. choice
Cancer Z
Type X
No cancer, not healthy
1. choice
Disease 1
2. choice
Disease 2
No cancer
3. choice
Disease 3
Disease 1
Cancer
Healthy
not
1. choice
Healthy
confirmed 2. choice
Healthy
3. choice
Cancer XYZ Healthy
Loc Program (Spectra Pool)
Proposal for the most likely spectrum match

Confirmation of a non-cancer condition (healthy)

Differentiation to inflammation, chronic diseases

Selection of type of cancer
Matching Spectra Search for Identification of Cancer
Localization resp. other Diseases or Healthy Persons
Decision making:
The final diagnosis (cancer confirmation; cancer type/localization; no cancer/not healthy; healthy)
can be made after consideration of the biophysical parameters (DR, DRN etc.) and especially the
LOC pool matches.
Score
3,78
1,15
1,23
0,82
0,41
-1,13
•
Result
Healthy
probably no cancer
probably no cancer
Cancer
Cancer
Cancer
Pool Match (cancer type, order of match)
DRN
DR
Score
4,43
2,55
-0,66
0,54
-2,83
-3,13
Result
Healthy
Healthy
Cancer
no cancer, not healthy
Cancer
Cancer
Diagn 1
Healthy
Inflammat
Breast
AI Disease
Lymphoma
Lung Ca
Diagn 2
Healthy
Diagn 3
Healthy
Ovarian Ca Colon Ca
Sclerodermia
Prostate
Bladder Ca
Colon Ca
Stomach Ca
Final Match Result
(from analytical point of view)
Healthy
Chronically: Inflammation
Have cancer: Breast Ca
Chronically: Autoimmune disease
Have cancer: Lymphoma Ca
Have cancer: Stomach Ca
With the EPR/ESR biomarker it becomes possible to specifically identify each type of cancer
through the targeted EPR/ESR spectra analysis and the matching with the most comparable
cancer spectrum in a patients spectra pool bank LOC Pool. Sufficient reference spectra of
different individuals (healthy group, chronically ill group, cancer group) must available in the
spectra data pool LOC).
The more EPR/ESR spectra are available, the more reliable are the results of identification.
Cancer Localization by EPR/ESR
The EPR/ESR biomarker test has the potential to localize the malign process by matching the
spectra of patients with a pool of well described reference spectra (Loc Pool: in 2016 based on
approx. 2.400 EPR/ESR spectra).
EPR/ESR Results – Printout of the Data Sheet
Name
L.E.
MMS-System
Age
9
Gender
male
ID
30070100
01.01.2016
DR
RTQ (%)
BE (%)
DTE (%)
(>1,5)
(80-100)
(65-136)
(40-175)
6,34
94
110
118
LOC Match Match Order (Diagnosis 1 - 3, order value)
DRN
Diagn 1
Healthy
0,00000
(>2,0)
Diagn 2
Healthy
0,00000
4,59
Diagn 3
Healthy
0,00000
Match Classification
Diagnostic Proposal (ICD)
Healthy
0,00000
yes
Chronic
0,00000
no
Cancer
>10
no
LOC Result
Healthy
Explanations on the back page
DR
<1,0 cancer
>1,0 to <1,2 probably no cancer
>1,0 healthy
RTQ (real transport quality)
BE (binding efficiency)
DTE (detoxification efficiency)
DRN
<0,0 cancer
>0,0 to <2,0 no cancer, but not healthy
>2,0 healthy
LOC Result (Final Match Result)
Healthy
Chronically ill: Diagnosis
Have cancer: Cancer type
EPR/ESR Results – Printout of the Data Sheet
Name
L.E.
MMS-System
Age
9
Gender
male
ID
30070100
01.01.2016
DR
RTE (%)
BE (%)
DTE (%)
(>1,5)
(80-100)
(65-136)
(40-175)
6,34
94
110
118
LOC Match Match Order (Diagnosis 1 - 3, order value) Name
Age
S.F.
44
DRN
Diagn 1
Healthy
0,00000
MMS-System
(>2,0)
Diagn 2
Healthy
0,00000
4,59
Diagn 3
Healthy
0,00000
DR
RTQ (%)
Match Classification
Diagnostic Proposal (ICD)
(>1,5)
(80-100)
Healthy
0,00000
yes
1,16
66
Chronic
0,00000
no
LOC Match Match Order
Cancer
>10
no
DRN
Diagn 1
LOC Result
Healthy
(>2,0)
Diagn 2
Explanations on the back page
1,34
Diagn 3
DR
<1,0 cancer
Match Classification
>1,0 to <1,2 probably no cancer
Healthy
0,00000
>1,0 healthy
Chronic
0,00629
RTQ (real transport quality)
Cancer
0,00808
BE (binding efficiency)
LOC Result
DTE (detoxification efficiency)
DRN
<0,0 cancer
>0,0 to <2,0 no cancer, but not healthy
>2,0 healthy
LOC Result (Final Match Result)
Healthy
Chronically ill: Diagnosis
Have cancer: Cancer type
Gender
female
ID
96953600
01.01.2016
BE (%)
DTE (%)
(65-136)
(40-175)
79
101
(Diagnosis 1 - 3, order value)
Healthy
0,00000
CHR
0,00492
Cancer
0,00852
Diagnostic Proposal
Healthy
no cancer, but not healthy
Colon Cancer
Chronically ill: Inflammation
EPR/ESR Results – Printout of the Data Sheet
Name
L.E.
MMS-System
Age
9
Gender
male
ID
30070100
01.01.2016
DR
RTE (%)
BE (%)
DTE (%)
(>1,5)
(80-100)
(65-136)
(40-175)
6,34
94
110
118
LOC Match Match Order (Diagnosis 1 - 3, order value) Name
Age
DRN
Diagn 1
Healthy
0,00000 S.F.
44
(>2,0)
Diagn 2
Healthy
0,00000 MMS-System
4,59
Diagn 3
Healthy
0,00000
DR
RTE (%)
Match Classification
Diagnostic Proposal (ICD)
(>1,5)
(80-100)
Healthy
0,00000
yes
1,16
81
Chronic
0,00000
no
Match
Order
LOC Match
Cancer
>10
no
DRN
Diagn 1
LOC Result
Healthy
(>2,0)
Diagn 2
Explanations on the back page
1,34
Diagn 3
DR
<1,0 cancer
Match Classification
>1,0 to <1,2 probably no cancer
Healthy
0,00000
>1,0 healthy
Chronic
0,00629
RTQ (real transport quality)
Cancer
0,00808
BE (binding efficiency)
LOC Result
DTE (detoxification efficiency)
Gender
female
ID
96953600
01.01.2016
BE (%)
DTE (%)
(65-136)
(40-175)
79
101
(Diagnosis 1 - 3, order value)
Healthy
0,00000
CHR
0,00492
Name
Age
Gender
ID
Cancer
0,00852
A.S.
56
male
99999800
Diagnostic Proposal
MMS-System
01.01.2016
Healthy
DR
RTQ (%)
BE (%)
DTE (%)
no cancer, but not healthy
(>1,5)
(80-100)
(65-136)
(40-175)
Colon Cancer
-1,63
45
60
34
Chronically ill: Inflammation
LOC Match Match Order (Diagnosis 1 - 3, order value)
DRN
DRN
<0,0 cancer
>0,0 to <2,0 no cancer, but not healthy
>2,0 healthy
LOC Result (Final Match Result)
Healthy
Chronically ill: Diagnosis
Have cancer: Cancer type
Diagn 1
(>2,0)
Diagn 2
-1,28
Diagn 3
Match Classification
Healthy
0,00583
Chronic
0,00560
Cancer
0,00370
LOC Result
Cancer
0,00370
CHR
0,00560
Healthy
0,00583
Diagnostic Proposal
Healthy
no cancer, but not healthy
Colon Cancer
Have cancer: Stomach
Therapy Monitoring and Follow Up
The test can also be used for therapy monitoring and follow up of cancer diseases:
• For a therapy monitoring and follow-up of cancer disease the question arises of
whether and to what extent the EPR/ESR test can analyze an appropriate therapy or
the progress of a malignancy.
• After detection of a cancer / malignant process and its localization in the body by the
EPR/ESR test an assessment of therapy is possible
 Monitoring of therapeutic effect (before / after resection of a cancerous tumor;
before / during / after chemotherapy)
 Individualization of therapy (effectiveness of treatment, resistance, bioavailability
of drugs, reduction of drug toxicity).
• During the cancer aftercare it has the potential for detection and localization of
suspected recurrences and metastases
 Follow-up of patients with known cancer diseases
 Prediction of therapeutic effectiveness
 Early detection of relapse
 Long-time observation.
Therapy Monitoring – Case Report
Patient: female, 35 years, malignant lymphoma
Cut off for DR<1
9/29/2000
8
7.95
no evidence
of relapse
11/21/2000
12/16/2000
6
4
4/16/2004
7/4/2003
11/11/2002
2.30
after start of therapy
3.09
0
2.59
5.21
4.20
1.59
1.35
2.20
8/16/2002
1/11/2002
5.73
1/19/2001
6.40
2/10/2001
5.10
5.24
3/25/2002
12/30/2000
-0.46
-2
5.15
4.53
cancer diagnosed
12/17/2000
2
2.9
1/14/2003
Integral Discrimination
Parameter - DR
3/4/2001
therapy finished
9/1/2001
11/22/2001
Example for therapy monitoring: Lymphoma was detected by EPR/ESR Test,
confirmed by other means. Successful chemotherapy, DR>1 indicates
positive therapy influence, confirmed by clinical data.
Therapy Monitoring – Case Report
Patient: female, 64 years, sigma cancer
11-Jul-14
Cut off for DR<1
Integral Discrimination
Parameter - DR
8
6
cancer diagnosed
4
17-Jan-15
No evidences of
tumor/metastasis
2
5.0
22-Aug-14
0 0.9
3.9
-2
after tumor resection
-4
2.6
chemotherapy started
3.6
6-Nov-14
23-Sep-14
3.8
6-Nov-14
Example for therapy monitoring: Sigma cancer was detected by other
means, confirmed by EPR/ESR Test. Successful resection, DR>1
indicates positive therapy, no metastases, confirmed by clinical data.
Therapy Monitoring – Case Report
Patient: male, 84 years, stomach cancer
15.03.02
Cut off for DR<1
8
20.01.03
25.04.02
6
Integral Discrimination
Parameter - DR
after 1st chemo
therapy cycle
4
2
16.05.02
0
-0,6-2
-0,4 0,9
-4
-0,4
0,9
07.11.02
therapy finished,
tumor had not
changed
-0,4
-0,6
14.06.02
after 2nd chemo
therapy cycle
-0,4
10.07.02
22.08.02
Example for therapy monitoring: First EPR/ESR Test after diagnosis of
relapse of a stomach cancer. Chemotherapy did not influence the tumor
development, DR remains at <1, confirmed by clinical data.
Conclusion of an EPR/ESR Therapy Monitoring
(General Hospital Beeskow, Germany, Prof. Dr. Koch)
EPR/ESR
Clinical situation concerning therapy
and prognosis
(before/after therapy)
DR <1
DR>1

successful tumor therapy, good
prognosis, curative therapy possible

slow progression of tumor growth
and metastases formation, longer
survival period

aggressive growth in primary
tumor and/or metastasis, bad
prognosis, short survival period
RTE > 60%
-1 < DR < 1
30%< RTE <60%
DR < -1
RTE < 30%
DTE < 15%
Source: Krankenhaus Beeskow, Germany, 2009..
Follow-up, Relapse Control – Case Report
Patient: female, 52 years, breast cancer relapse, therapy
Cut off for DR<1
09.07.2000
11.04.2002
Integral Discrimination
Parameter - DR
8
23.09.2000
6
4
25.10.2000
4,8
2
11.01.2002
relapse discovered
in Jan 2001,
therapy started
0
-1,9
tumor progresses,
no therapy effect
-1,7
-2
-4
02.12.2000
-0,4
4,8
-1,4
-0,7
-0,4
-0,7
29.11.2001
19.01.2001
-0,6
0,6
6,2
24.10.2001
10.02.2001
1,6
24.09.2001
17.08.2001
5,7
30.07.2001
4,1
08.03.2001
20.04.2001
10.05.2001
after 2nd
chemotherapy cycle
28.06.2001
Example for relapse control: Relapse 10 years after cancer first detected by
EPR/ESR Test, confirmed by other means. First cycle of chemotherapy has a
positive effect but DR returns to <1. Second cycle has only short effect, situation
deteriorating, DR<-1, patient died two months later.
Conclusion
1. EPR / ESR spectroscopy of albumin patterns is a specific
and sensitive noninvasive biomarker/tumor marker (more
than 1.200 patients with cancer types have demonstrated
specific changes to albumin in that patients which correlate with tumor activity, and the clinical outcome.
2. The EPR/ESR biomarker test has the potential for a/an
• differentiation between healthy, chronically ill, and
cancer people - detection of primary tumors,
• very early cancer diagnosis, detection of hitherto
undetected cancer,
• screening of people with a high risk of cancer
• identification of cancer localization,
• therapy monitoring of cancer diseases,
• follow-up of patients with known cancer diseases,
• aftercare at suspected recurrence and metastasis.
Bibliographic References – Publications
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MATTHES G, SEIBT G, MURAVSKY V: Analysis of Plasma Proteins and Tumor Screening Diagnostic Using ESR. New Drugs 2001;2:26-32.
MATTHES G, SEIBT G, MURAVSKY V: Quality analysis of plasma products and derivatives by electron spin resonance spectroscopy (ESR).
Infusionsther Transfusionsmed 2001;28:247.
MATTHES G, SEIBT G, MURAVSKY V, HERSMANN G, DORNHEIM G: Albumin transport analysis of different collected and processed plasma
products by electron spin resonance spectroscopy. Transfusion and Apheresis Science 2002;27:129-135.
MATTHES G, SEIBT G, MURAVSKY V, SIEGEL G, UNKELBACH U: Assessment of albumin transport/binding function. VII. European Congress of the
International Society of Blood Transfusion, July 5-9, 2003, Istanbul, TK.
MURAVSKY V, MATTHES G, SEIBT G, HURACHEUSKAYA T: Electron Spin Resonance Method for in vitro Determination of Albumin Transport
Function, Detoxification January 2004, No.1 Vol.1.
MATTHES G, SCHNURR K, SIEWERT U, FISCHER G: Cancer screening of blood donors by electron spin resonance spectroscopy. Vox Sanguinis
2004;87(Suppl. 3), 56.
MATTHES G, SEIBT G, MURAVSKY V, SIEGEL G, UNKELBACH U: Assessment of albumin transport/binding function. Vox Sanguinis 2004;87(Suppl.
3),2.
DAVIES NA, SCHNURR k, SEN S, HODGES SJ, MATTHES G, JALAN R: Serum albumin shows conformational, structural and functional abnormalities
in cirrhotic patients, which worsen with severity of liver disease and are unaffected by albumin dialysis. Hepatology 2005;42(4)suppl.1,222A.
SEIDEL P, GURACHESVSKY A, MURAVSKY V, SCHNURR K, SEIBT G, MATTHES G: Recognition of malign processes with neural nets from ESR
spectra of serum albumin. Z Med Phys 2005;15:265-272.
SCHNURR K, MURAVSKY V, SEIBT G, MATTHES G: The analysis of functional characteristics of serum albumin – a novel possibility of early cancer
diagnosis. In: K. Conrad, M Bachmann, W Lehmann, U Sack (eds): Methods, possibilities and perspectives of pre-symptomatic tumor diagnosis.
Pabst Science Publishers Lengerich, Berlin, Bremen, Miami, Riga, Viernheim, Wien Zagreb 2005, p. 225-234.
MATTHES G, EICHHORN I, SCHNURR K: Cancer screening of blood donors by electron spin resonance spectroscopy (ESR/EPR). Transf Med
Hemother 2006;33(Suppl 1):308.
KAZMIERCZAK ST, GURACHEVSKY A, MATTHES G, MURAVSKY V: Electron Spin Resonance Spectroscopy of Serum Albumin: A Novel New Test for
Cancer Diagnosis and Monitoring. Clin Chem. 2006 Nov;52(11):2129-34. Epub 2006 Sep 21.
GURACHEVSKY A, MURAVSKY V, MATTHES G: Changes in serum albumin measured by electron spin resonance: In vitro diagnostic EPR Test. Proc
lntl Soc Mag Reson Med 2007;15:1323.
MURAVSKY V, GURACHEVSKY A, MATTHES G: Disease specific albumin patterns defined by electron spin resonance. Tumor Biol
2007;28(suppl.1):19.
GURACHEVSKY A, KAZMIERCZAK SC, JÖRRES A, MURAVSKY V: Application of spin label electron paramagnetic resonance in the diagnosis and
prognosis of cancer and sepsis. Clin Chem Lab Med. 2008;46(9): 1203-10. PMID: 18783341.
JALAN R, SCHNURR K, MOOKERJEE RP, SEN S, CHESHIRE L, HODGES S, MURAVSKY V, WILLIAMS R, MATTHES G, DAVIES NA: Alterations in the
functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality. Hepatology. 2009 Aug;50(2):55564.
MURAVSKY V, GURACHEVSKAYA T, BEREZENKO S, SCHNURR K, GURACHEVSKY A: Fatty acid binding sites of human and bovine albumins:
Differences observed by spin probe ESR. Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy 2009;74(1):42-47. PMID:
19540798.
SCHNURR K, WATERSTRADT K: Krebsdiagnostik durch funktionelle Analyse von Serumalbumin. Laborwelt 2009;22(4):22-24.
MOERGEL M, KAMMERER PW, SCHNURR K, KLEIN MO, AL-NAWAS B: Spin electron paramagnetic resonance of albumin for diagnosis of oral
squamous cell carcinoma (OSCC). Clin Oral Investig 2012;16:1529-1533. PMID: 22160580.
GELOS M, HINDERBERGER D, WELSING E, BELTING J, SCHNURR K, KLEIN MO, AL-NAWAS B: Analysis of albumin fatty acid binding capacity in
patients with benign and malignant colorectal diseases using electron spin resonance (ESR) spectroscopy. Int J Colorectal Dis 2012;25:119-127.
PMID: 19644694.
Bibliographic References – Presentations
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7.
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10.
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13.
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MATTHES G, SEIBT G, MURAVSKY V: Analyse der Albumintransportfunktion in Plasmaprodukten durch Elektronen-Spin-Resonanzspektroskopie. DGTI-Sektion Plasmatische Bestandteile. Deutsche Klinik für Diagnostik Wiesbaden, 16. Dezember 2000, Germany.
MATTHES G, SEIBT G, MURAVSKY V: Quality analysis of plasma products and derivatives by electron spin resonance spectroscopy (ESR).
International Symposium on Advances in Transfusion Safety. Paul-Ehrlich-Institute, Langen, June 06-08, 2001, Germany.
MATTHES G, SEIBT G, MURAVSKY V: Analyse von Plasmaproteinen und Krebsfrühdiagnostik mittels Elektronenspinresonanzspektroskopie
(ESR). TGZ-Workshop, Wildau, 30.Juli 2001, Germany.
MATTHES G, SEIBT G, MURAVSKY V: Albumin transport analysis in plasma products and derivatives by electron spin resonance
spectroscopy (ESR). 13th ESFH/S.I.D.E. Congress. September 16-19, 2001, Riva del Garda-Trento, Italy.
MATTHES G, SEIBT G, MURAVSKY V, SIEGEL G, UNKELBACH U: Assessment of albumin transport/binding function. VIII European Congress
of the International Society of Blood Transfusion. July 05-09, 2003, Istanbul, Turkey.
SCHNURR, K, SEIBT G, MURAVSKY G, MATTHES G: Die MMS-Technologie ein neues Verfahren zur präsymptomatischen Tumordiagnostik.
2.Innovationsforum Präsymptomatische Tumordiagnostik, 1.-2.September 2003, Jena, Germany.
MURAVSKY V, GURACHEUSKAYA T, GURACHEUSKY A: Functional analysis of albumin in plasma products by electron spin resonance
spectroscopy. 47.Jahrestagung der Arbeitsgemeinschaft der Ärzte staatlicher und kommunaler Blutspendedienste, 3-5 March, 2004,
Leipzig, Germany.
SCHNURR K, SIEVERT U, FISCHER G, MATTHES G: ESR-Analyse von Rückstellproben karzinomerkrankter Blutspender. 47.Jahrestagung der
Arbeitsgemeinschaft der Ärzte staatlicher und kommunaler Blutspendedienste, 3-5 March, 2004, Leipzig, Germany.
MATTHES G, SCHNURR K, SIEWERT U, FISCHER G: Cancer screening of blood donors by electron spin resonance spectroscopy. XXVIII
Congress of the International Society of Blood Transfusion, 11-15 July, 2004, Edinburgh, United Kingdom.
MATTHES G, SEIBT G, MURAVSKY V, SIEGEL G, UNKELBACH U: Assessment of albumin transport/binding function. XXVIII Congress of the
International Society of Blood Transfusion, 11-15 July, 2004, Edinburgh, United Kingdom.
SCHNURR K, SEIBT G, MURAVSKY V, MATTHES G: A new approach in cancer diagnostics: Analysis of functional properties of albumin.
20.Jahrestagung der deutschen Gesellschaft für biomedizinische Technik, 22-24 September, 2004, Ilmenau, Germany.
MATTHES G: Diagnostische Möglichkeiten der ESR-/EPR-Analyse von Albumin. Workshop „Neue Methoden zur Früherkennung, Therapieund Rezidivkontrolle von Krebserkrankungen“. 03.Dezember 2004, TGZ Wildau, Wildau, Germany.
MATTHES G: New revival of albumin? International Plasma Protein Congress (IPPC) 2015, March 8-9, 2005, Berlin, Germany.
DAVIES NA, SCHNURR K, CHESHIRE LM, HODGES SJ, MATTHES GA, JALAN R: Albumin function is significantly reduced with increasing
severity of liver disease. British Liver Society/BASL ANNUAL MEETING 2005. September 8-9, 2005, London, United Kingdom.
MATTHES G: ESR/EPR Biomarker Technology – Electron Resonance Spectroscopy of Albumin. Lecture at King Abdulaziz University Hospital
& Oncology Center Jeddah, September 26th, 2005. Jeddah, Saudi-Arabia.
DAVIES NA, SCHNURR K, SEN S, HODGES SJ, MATTHES G, JALAN R: Serum albumin shows conformational, structural and functional
abnormalities in cirrhotic patients, which worsen with severity of liver disease and are unaffected by albumin dialysis. 56th Annual Meeting
of the American Association for the Study of Liver Diseases, November 11-15, 2005, San Francisco, USA.
MATTHES G, EICHHORN I, SCHNURR K: Cancer screening of blood donors by electron spin resonance spectroscopy (ESR/EPR).
39.Jahrestagung der Deutschen Gesellschaft für Transfusionsmedizin und Immunhämatologie. September 11-15, 2006. Frankfurt/M,
Germany.
MURAVSKY V, GURACHEVSKY A, MATTHES G: Disease specific albumin patterns defined electron spin resonance. 35th Meeting Int. Soc.
Oncodevelopmental Biology and Medicine (ISOBM). September 15-19, 2007, Prague, Czech Republic.
LECKIE P, HODGES SJ, CHESHIRE LM, MOOKERJEE RP, MATTHES G, JALAN R, DAVIES NA: Ischemia Modified Albumin Predicts Mortality in
Liver Disease Patients. 10th International Symposium on Albumin Dialysis (ISAD), September 12-14, 2008, Rostock-Warnemünde,
Germany.