Learn about a new approach to evaluating cancer that uses common biomarkers, but evaluates them using system theory. It looks as cancer as a whole-body disease expressed at the level of the cells, rather than a cellular disease expressed throughout the body.

1. Laura Buehning MD, MPH, Kamyar M. Hedayat, MD, Aarti
Sachdevi, Shah Golshan PhD, Jean Claude Lapraz, MD
Presentation by:
Kamyar M. Hedayat, MD
President,American Society of Endobiogenic Medicine and
Integrative Physiology
“Research is to see what everybody else has seen and to think what
nobody else has thought.” — Albert Szent-György
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3. scanning electron microscope, shows T cells (orange) attached to a tumor cell.
http://www.mskcc.org/blog/cancer-immunotherapy-named-science-magazine-breakthrough-year
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4. IF…
Cancer
= Abnormal cellular activity
Chemotherapy, Radiation, Surgery
= CURE of ALL cancers, EVERY TIME.
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! Short-term survival is improving BUT
! We see more
◦ New onset, late stage cancer IN…
◦ Younger populations WITH…
◦ Increasing relapses and metastasis
Formula from: Hanin, L and Zaider, M. Effects of surgery and chemotherapy on metastatic progression of prostate cancer: Evidence
from the natural history of the disease reconstructed through mathematical modeling. Cancers 2011(3):3632-3660

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7. Imaging: Structural Imaging: Functional
PET-CT: Left internal jugular node metastases
with extranodal invasion;Akira Kouchiyama,
http://commons.wikimedia.org/wiki/File:PET-
CT_scanning_of_lymph_node_metastases_in_cancer.jpg
Breast Cancer, Mammography
Astrocytoma, Rt Frontal Lobe, MRI
Breast Cancer,: University Medical Imaging Group
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8. Histology
Infiltrating ductal carcinoma of breast
Hematologic, Gross
Circulating tumor cells:A-C: Prostate cancer, D:
Metastatic lung cancer; PNAS v.107 (43), 2010
Oncobiologic
Survivn protein and apoptosis regulation
Telomerase and immortality
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9. ! Unifactorial—Cancer multifactorial
! Lacks global vision of physiology
! Reactive modality
! Lacks predictive assessment
! Downstream: Does not determine
causative factors
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10. Hematologic: cell-free DNA
DNA Methylation patterns
MicroRNA: Microarray, PCR
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11. http://rams.biop.lsa.umich.edu/research/metabolomics
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12. ! Advantages:
◦ Reinforce concept of cancer as complex and
multi-factorial
◦ Nuanced, sensitive and specific
◦ Individualized
! Shortcoming
◦ STILL Reductionist: views cancer at the level
of the cell
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13. ! Evaluate cancer as Systemic
disease expressed in cells
! Use GLOBAL systems
approach
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15. ! Quantitative
! Function of the parts
! Hierarchy
! Categorical
! Separate
! Independent
! Static
! Control
! Qualitative
! Function of the
System
! Relationships
! Individualized
! Interconnected
! Interdependence
! Dynamic
! Creative chaos
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Reductionism Holism

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Creation of Structure
Maintenance of STRUCTURE
Functional adaptation

18. ! Endocrine system
! Sole system to possess:
1) Ubiquity of interaction with each structural
element
2) Constancy of regulation of those elements
3) Constancy of regulation of itself
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19. ! The illness
◦ Exogenous factors
◦ Rate of development
◦ Degree Invasiveness
! The patient
◦ Endogenous factors
◦ Adaptation capability of terrain
◦ Evolution of terrain over time
! Illness + Patient
◦ Degree of coexistence
◦ Levels of adaptation activities in structure vs. function
◦ Dominance of one over the other
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METABOLISM
CATABOLISM ANABOLISMANABOLISM CATABOLISM
CRH
ACTH
ADRENALS
LHRH
FSH LH
GONADS
TRH
TSH
THYROID
GHRH
GH PL
PANCREASπΣ
αΣ
βΣ
Corticotropic Gonadotropic Thyrotropic Somatotropic
ANS
ENDOCRINE MANAGEMENT
20

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22. The purpose of the Biology of
Functions is to quantify the
functional abilities of the
organism, before and after the
effects of adaptation. Because it
is in permanent movement,
functionality can only be
measured by a dynamic,
integrated and evolutionary
methodology.
--C. Duraffourd and JC Lapraz
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23. ADVANTAGES
! Objective
! Quantitative
! Accurate
! Reproducible
! Minimally invasive
DISADVANTAGES
! Binary
! Reductionist
! Confusion of
◦ Cause vs. Effect
◦ Cause vs. Effect vs.
Mechanism
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25. Origin Biomarker
Bone Marrow
Red blood cell
White blood cell, total
Neutrophil
Lymphocytes
Eosinophils
Monocytes
Basophils
Hemoglobin
Platelets
Marrow-Blood interaction Erythrocyte sedimentation rate
Bone Stroma Enzymes
Osteocalcin
Alkaline phosphatase bone isoenzyme
General Enzymes Lactate dehydrogenase
Creatine phosphokinase
Endocrine: Pituitary Thyroid stimulating hormone
Electrolytes
Potassium
Calcium, total serum
70% bone
and blood
30% other
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26. DIRECT relationship of biomarkers
! Genital Ratio (GR)
◦ RBC/WBC
! Genito-Thyroid
◦ % Neutrophils / % Lymphocytes
INDIRECT Relationship of
Biomarkers ± Direct indexes ± Indirect indexes
! Catabolism/Anabolism ratio
= Genito-Thyroid / Genital ratio corrected
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28. ! Retrospective Case Control Design
◦ 92 patients in a single practice
◦ All types of cancers (hematologic and non-
hematologic)
◦ Age and sex-matched controls
◦ Three arm study
" Active Cancer (n=33)
" Cancer remission (n=13)
" Control group (n=46)
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29. ! Biology of Functions were available for all
92 patients
! 62 of 150 indexes were selected for
relevance to oncobiology
! Paired Wilcoxin Rank Sum
◦ Active Cancer vs. Control
◦ Remission vs. Control
! Independent Wilcoxin Rank Sum
◦ Active Cancer vs. Remission
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30. Table 1. Baseline Characteristics of Cancer Cases and Matched Controls
N
MALES
FEMALES
AVE
AGE
STD
MIN
AGE
MAX
AGE
P-
VALUE
Cancer
Cases
46
19
27
54.15
13.48
9
78
0.705
Control
46
19
27
54.75
13.38
10
84
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31. CANCER DIAGNOSIS MALE FEMALE ACTIVE INACTIVE
Abdominal Sarcoma 1 1
Acute Lymphocytic Leukemia 1 1
B Cell Lymphoma 1 1
Bladder and Ureter Carcinoma 1 1
Breast Carcinoma 13 8 5
Cervical Carcinoma 1 1
Chronic NonHodgkin’s
Lymphoma
1 1
Chronic Lymphocytic Leukemia 1 1 2
Colon Carcinoma 5 4 1
Hepatocellular Carcinoma 2 2
Liposarcoma 2 2
Lung Carcinoma 1 1
Melanoma 1 1
Myelodysplastic Syndrome 1 1
Ovarian Carcinoma 1 1
Parathyroid Carcinoma 1 1
Prostate Carcinoma 6 2 4
Renal Cell Carcinoma 1 1
Stomach Carcinoma 1 1
Testicular Carcinoma 1 1
Thalamic Glioblastoma 1 1
Uterine Carcinoma 1 1
TOTAL = 46 19 27 33 13
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32. Adaptation:
βMSH/αMSH Index (6-8): It expresses the
relative level of participation of the beta- and
alpha-melanocyte stimulating hormones (MSH) in
directly stimulating cortisol activity vs. the general
adaptation syndrome at the level of the pituitary.
Immunity:
! Proinflammatory index (0.1-0.4):The pro-
inflammatory index looks at the endogenous
potential for inflammation due to thyrotropic
over-activity and the degree to which cortisol is
able to compensate for this
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33. Anabolic Hormones:
! Estrogen fraction #5 (7-20): It expresses the
relative part of estrogens consecrated to the
growth of tissues and organs.
! Comparative Genital Androgeny index
(0.1-0.3): It indicates the metabolic activity of
androgen receptors at the tissue level and the
anabolism of tissue.
Catabolic hormones:
! Thyroid Index (3.5-5.5): It indicates the degree
of efficiency of thyroid hormones in managing the
metabolic energetic activity of the cell
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34. Anabolic-Catabolic endocrine harmony:
! Genito-Thyroid Index (1.5-2.5) (=PMN/
Lymphocytes): It expresses the relative
activity of the gonads in relationship to that
of the thyroid.
Metabolism:
! Catabolism/Anabolism Index (1.8-3): It
expresses the relative catabolic activity in
relation to that of anabolic activity within
the scheme of global metabolism of the
organism
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35. INDEX
N
TOTAL
CASES
MEAN±STD
TOTAL
CONTROLS
MEAN±STD
PVAL
Estrogen Fraction #5
45
18.64±16.87
10.58±5.30
0.004*
Genito-Thyroid Index
45
3.46±2.68
2.25±0.85
0.005*
Comparative Genital Androgeny
36
2.27±3.81
7.12±11.6
0.007*
Thyroid Index
39
5.17±3.64
3.72±1.73
0.039*
Beta MSH/Alpha MSH Index
39
5.64±3.86
4.11±1.98
0.042*
Catabolism/Anabolism Index
45
6.11±9.95
2.997±1.57
0.050*
Proinflammatory Index
42
1.64±2.80
0.73±0.70
0.056
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36. INDEX
N
ACTIVE
MEAN±STD
CONTROLS
MEAN±STD
PVAL
Estrogen Fraction #5
32
21.47±19.15
10.91±5.78
0.007*
Genito-Thyroid Index
32
3.70±3.05
2.32±0.80
0.067
Comparative Genital Androgeny
26
2.75±4.37
8.03±13.3
0.06
Thyroid Index
27
5.90±4.06
3.64±1.98
0.009*
Beta MSH/Alpha MSH Index
27
6.45±4.30
4.00±2.25
0.012*
Catabolism/Anabolism Index
29
6.82±12.11
3.09±1.70
0.198
Proinflammatory Index
29
1.91±3.26
0.72±0.54
0.249
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37. INDEX
N
ACTIVE
MEAN±STD
CONTROL
S MEAN
±STD
PVAL
ACTIVE
VS
INACTIVE
Estrogen Fraction #5
13
11.68±4.73
9.77±3.96
0.310
0.437
Genito-Thyroid Index
13
2.86±1.32
2.07±0.97
0.006*
0.622
Comparative Genital
Androgeny
10
1.03±1.05
4.74±4.21
0.028*
0.568
Thyroid Index
12
3.51±1.58
3.89±0.99
0.433
0.006
Beta MSH/Alpha MSH
Index
12
3.83±1.59
4.38±1.20
0.433
0.003
Catabolism/Anabolism
Index
14
3.47±1.77
2.85±1.74
0.363
0.910
Proinflammatory Index
13
1.04±1.25
0.74±1.01
0.019*
0.990
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38. INDEX N
TOTAL CASES
MEAN±STD
TOTAL
CONTROLS
MEAN±STD
PVAL
Estrogen Fraction #5 13 23.29±22.89 11.38±7.24 0.03*
Genito-Thyroid Index 13 3.56±1.98 2.35±0.81 0.25
Comparative Genital Androgeny 13 2.14±2.95 6.38±12.61 0.24
Thyroid Index 13 5.45±5.66 4.50±2.05 0.64
Beta MSH/Alpha MSH Index 13 5.99±5.97 5.02±2.35 0.70
Catabolism/Anabolism Index 13 4.94±4.80 3.24±1.96 0.38
Proinflammatory Index 13 1.25±1.73 0.71±0.48 0.94
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39. INDEX N
TOTAL CASES
MEAN±STD
TOTAL
CONTROLS
MEAN±STD
PVAL
Estrogen Fraction #5 5 20.60±21.18 7.20±1.48 0.23
Genito-Thyroid Index 5 3.51±1.45 2.03±0.64 0.14
Comparative Genital
Androgeny
4 2.61±4.28 14.50±21.79 0.07
Thyroid Index 5 6.08±5.23 2.42±1.21 0.23
Beta MSH/Alpha MSH Index 5 6.51±5.18 2.66±1.42 0.23
Catabolism/Anabolism Index 5 6.69±4.83 2.40±1.07 0.23
Proinflammatory Index 5 1.23±0.92 0.65±0.40 0.23
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40. ! Genito-Thyroid index =
Neutrophil to Lymphocyte ratio
! Over 400 studies in cancer patients,
predictive of mortality
! Also studied in Chronic Heart Failure,
Diabetes mellitus, etc.
! Considered a general, non-specific marker
of inflammation
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42. ! Genito-Thyroid, as the Neutrophil/Lymphocyte ratio is
incorporated into a series of indices that have relevance
to numerous disorders, including cancer
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Neutrophil to Lymphocyte Ratio =
Genito-Thyroid index
Catabolism/Anabolism Index
Cortisol index
Adrenal Cortex Index
Metabolic yield
Somatostatin
index
Histamine index
Ischemia Index

43. ! Theory of Endobiogeny offers a whole-
system approach to cancer
! In a retrospective, case-controlled study of
all cancer types, Biology of functions
distinguishes cancer patients from controls
! Future studies should look at homogenous
cancer patients vs. controls to better
characterize specific cancer types, and sub-
groups of responders and non-responders to
chemotherapy
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