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Naturopathic Oncology
How to Understand
and Treat Cancer from
a Molecular Basis
Speaker: Serge Jurasunas N.D. M.D. (Hom)
Member of the Society of Integrative Oncology
American Naturopathic Medical Association
www.sergejurasunas.com
International Physician’s Round Table
29-31 january 2016
Tampa - Florida
1
Any intelligent fool can make things bigger
and more complex...
It takes a touch of genius and a lot of courage
to move in the opposite direction.
Albert Einstein
2
Lecture Overview
→ What is cancer?
→ What does metastasis mean?
→ The need for new diagnostics
→ P53 Tumor supressor gene
→ Novel approach to cancer with dietary agents
→ Clinical cases
3
1938 American Society for the
Control of Cancer poster
Problems of Conventional Oncology
→ Multi-drug resistance
→ Radiotherapy resistance
→ Occurrence of metastases
→ Recurrence of the tumor still too high
→ Metastatic cancer is incurable
4Cancer is Becoming an Epidemic Disease
What Cancer Means?Carcinoma derived from the Greek Karkinos – Crab: Hippocrates (460-375 B.C.)
Cancer defines a population of
abnormal, damaged cells that have
lost their normal control and
differentiation and are non
specialized, divide unchecked,
evade apoptosis, accumulate
mutations and start to proliferate.
5
Before a cell divides, the DNA is
checked to make sure it has
replicated correctly.
If DNA does not copy itself correctly,
the cell divides incorrectly and gene
mutations occur.
Cancer is a Disease of the Cell Cycle
Katlilen Collins – Tyler Jacks and Nicolas P. Pavieltch. The cell cycle and cancer – Proc. Nath Acad Sci – USA – Vol 94 – 3776 –
3778 – April 19976
7
Second Question: What Does Metastasis Mean?
Metastasis is the process by which a
tumor cell leaves the primary tumor by
lack of addhesion, travels to a distant
site via the circulatory system and
establishes a second tumor.
Metastasis may enter into a dormancy
phase during several months or years.
Causes of suffering and usually
incurable by conventional treatment.
Metastasis are responsible for 90% of
cancer mortality.
Metastasis are Responsable for 90% of Cancer Mortality 8
9
Dormancy MetastasisStop in the GO resting state
10
Cancer Entering the Blood Stream and Being Carried
Elsewhere (Cancer Metastasis)
Breast Cancer Stage IV Primary Tumor with Metastasis – Disease Recurrence after 3 months, 3 years, 14
years. Lung, liver – Lung, Bones – Lung, Brain, etc.
11
A 37 year old woman was diagnosed in 2013 with a breast
cancer followed by a radical mastectomy, chemotherapy and
remission.
2015: Disease Recurrence
She is diagnosed with multiple lesions to bone and lung and
subjected to new chemotherapy with considerable suffering
and little hope for a cure.
12
Conventional Diagnostics
1. Inefficient in cancer prevention and
predicting disease recurrence.
2. Many cancers and pre-malignant
forms go undetected, asymptomatic
for many years .
3. Inefficient to monitor cancer cell
resistance to chemo/radiation.
4. Does not select the best adapted
treatment.
13
A 67 year old woman was diagnosed in April 2015 with a
pancreatic cancer (6 cm) with secondary nodulles to her liver. In
December, 2014 she underwent a complete medical check up with
no sign of disease. No symptoms.
A 38 year old woman was diagnosed in April 2015 with an
advanced gastric cancer of 16 cm with secondary large lesions of 8
cm to her liver. No symptoms.
14
Molecular Medicine and Cancer Biology
Molecular medicine is
important in order to detect
pre-malignant conditions
cancer initiation and/or in an
earlier stage before it starts
to proliferate and invade the
body.
P53
mutation
15
Molecular Markers in Cancer Diagnostics and Prevention
Not yet an option
but in many
publications,
clinical trials,
research,
congresses but
little clinical
application
16
The New Solution to Cancer
Activate the tumor suppressor genes’
own body defense to destroy cancer cells
through a natural programmed
mechanism called Apoptosis.
Selective destruction of cancer cells.
Apoptosis induction is recognized as the
most potent defense in our body against:
Cancer initiation
Tumor growth
Metastatic spread
17
Apoptosis: Our First Line of Defense Against Cancer
Robert Gel and David Vaux – Apoptosis in the development and treatment of cancer: Oxford Journal – Carcinogenesis, vol.26, issue 2 –
263-70 - 2004
The Tumour Suppressor “P53” Gene
“Guardian of our Genome”
Cancer Killer
Over 60.000 publications
Term coured by DP Lane – Nature 1992-July 2: 358 (638):156
19
The P53 Protein and Cancer
P53 is a tumor suppressor gene which instructs
genetically damaged cells to repair or die
through the apoptosis pathway.
P53 is a transcription factor for many genes
including pro-apoptotic and anti-apoptotic
genes BAX, BCL2, MDM2.
P53 is a short-lived and expressed at very low
levels in normal life. P53 expression is
activated and protein levels increase under
stress stimuli and a cell’s DNA damage.
Function of P53: Induced cell cycle arrest P21, etc.
DNA repair
Initiate apoptosis – Bax, PUMA, etc.
20
21
22
Pro-Apoptotic BAX Proteins – A
Tumor Suppressor Inactivated in Many Cancers A Key Player in Cell Death Induced by Anticancer Drugs
■ Bax gene expression is inactive in approximately one-third of invasive breast cancers (specimen of
150 patients) (1)
■ In another study of 119 women with metastatic breast cancer, patients whose tumor has lost Bax
activity had poor response to chemotherapy, faster time to progression and shorter overall
resistance.
■ Enhanced expression of Bax protein is associated with good response to chemotherapy/radiation
in vivo.
(1) John Red – Bax gene expression in breast cancer – The Burknam Institute for Medical
Research. Research project Award – Calif. Breast Cancer research program – 1995.
(2) Krajewski S., Blomquist C., Fransilla K. et al – Reduced expression of proapoptotic gene BAX is
associate with poor response rates to combination chemotherapy and shorter survival in women
with metastatic breast adenocarcinoma – Cancer Tes. 1995 – 55: 4471-4478
23
Predictive Value of BAX/BCL2 in
Chemo/Radiation Regimen
Cells that overexpress BAX enhance cell death.
Cells that overexpress BCL-2 reduce the susceptibility to apoptosis.
Because BAX proteins antagonize BCL-2’s anti-apoptotic function, it is likely that
BCL-2/BAX ratio determines the susceptibility of a cell to apoptosis and determines
the therapeutic response of chemo/radiation regimen to apoptosis stimuli.
Scopa, Chriscula, Vagionas, Constantine, Kardimaki, Dimitris, Kourelis, Athanasias C. – BCL-2/BAX ratio as
a predictive Marker for Therapeutic Response to radiotherapy in patient with rectal cancer –
Immunotochemistry x Molecular Morphology – Dec.2001 – Vol.9 – Issue 4 – 329-334
24
Function of Survivin as an Inhibitor of Apoptosis
Dobi T., Beltrami E., Wall N.R., Plescia J., Altieri D.C. – Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis – J. Clin invest.
2004: 114-1117 – 27.
25
Survivin: A New Biomarker Emerging as an Attractive
Diagnostic for Early Targeting of Cancers
■ Increased survivin expression is associated with lymph nodes, invasion,
metastases risk of recurrence and decreased overall survival in several
malignancies
■ Survivin detection can serve as an early marker of cancer, for detecting
metastases, breast cancer and prostate cancer recurrence
Yong-Gang L.V. – The role of survivin in diagnosis, prognosis and treatment of breast cancer. J.Thorac Dis.
2010 – 2: 100 - 110
26
Survivin in Breast CancerStudy done at St. Vincent’s University Hospital
University College Dublin (Irland) 2004120
90
60
30
0Normal Cancer Metastases
■ Survivin is virtually absent from normal
tissues
Very high levels in malignant breast
tumors
■ Study of 500 breast cancer patients:
Patients with high levels of survivin: reduced survival time and more subject to disease
recurrence
■ Strong predictor of poor prognosis
Hinnis A.R. Luckett J.C. Walker R.A. – Survivin is an independent predictor of short-term survival in poor
prognostic breast cancer patients – BR. J. Cancer 2007 – 96-639-45
27
Increasing Survivin Expression in Different Grades of Prostate
Carcinoma
Normal prostate
tissue
Primary grade
prostate
carcinoma
Primary high
grade prostate
carcinoma
High grade prostate
carcinoma
Associated with Aggressive Prostate Cancer
Ashfoq R., et al – Survivin is associate with feature of biologically aggressive prostate carcinoma –
Cancer – 2004 – 100 – 751 - 757
100%
80%
60%
40%
20%
0%
28
P53 Mutations in Cancer
■ P53 is the most commently
mutated gene harbored in more
than half of all cancers
■ P53 inactivate or mutated
appear necessary to develop
many forms of cancer
■ Restoring P53 WT function or
activation may offer a
therapeutic benefit
29
Gain of function means it stimulates growth factor receptors, upregulates genes that increase angiogenic
factors, increase cells proliferation, impair immune function and increase metastases invasion.
www.sergejurasunas.com (oncogenic function of mutant P53)
30
EGFR/Integrin
RAS
C-Myc
E-Cadherin
TGF. Beta
NF.KB
ID 4
E.2F1
P53
Mutation
Metastasis
Angiogenesis
Invasion
Anti-apoptotic proliferation
survival
Angiogenesis
Proliferation
Invasion
Decreased apoptosis
Decreased apoptosis
Proliferation
Promotes malignant
progression
Associated with
E.M.T.Immunosuppression
enhances motility
angiogenesis
Promotes invasiveness
and metastases
Increase evasion
Immunosuppression
Antiapoptotic
Inflammation Angiogenesis
Metastasis
Hallmarks of P53 Mutation
Promotes angiogenesis
Tumor proliferation
Promotes
angiogenesis
Copyright Serge Jurasunas 2012
P53 Mutations as Fingerprints of Environmental Carcinogens
Rengul Cetin – Atalay and Mehnet Ozturk – P53 mutations as fingerprints of environmental carcinogens – Pure APP.chem – Vol.72-nº6-PP995-999-200031
32
Growth of Xenograft Tumors
Tumors with intact
P53 gene regressed
during the treatment,
whereas the tumors
with delected P53
genes continued to
grow.
33
P53 Mutations Predict Outcome in Advance
65/93 Studies found that P53 is a statistically significant factor of poor prognosis in various cancers.
Studies have found that the presence of a mutation was associated with a poor response to various
chemotherapy or radiotherapy regimens in breast, colorectal, ovarian, stomach and soft tissue
carcinoma.
Texas researchers have found that high levels of P53 mutated protein accumulation are associated
with a significantly increased local recurrence rate in 1,500 breast cancer patients treated with
mastectomy.
P53 – Positive patients 21.5%
Negative patients 9.3%
14/19
34
Olivier et al – Prognostic and predictive value of P53 mutations in human cancer in: 25 years of P53 research – Kluwer Academic Publisherd in Press, Editors:
P. Hainaut K. Wiman 2005
35
Apoptosis in Tumors Treated with Cytotoxic Chemotherapy
is Driven by P53
36
P53 Mutation –
Causative Factors in the Progression of Cancer
■ Associated with increasing cancer cell resistance to chemotherapy
or other treatments that trigger apoptosis
■ Associated with metastatic potential, faster tumor growth and
invasiness
■ Associated with aggressive cancers such as breast, ovarian and
worst of all shorter survival
Conclusion:
Sood A.K., J.I. Dolan M. et al (1999) – Distant metastases in ovarian cancer Association with P53 mutations – Clin Res. 5 – 2485-2490.
Mazars B., Spinardi L., Beuchalch M., Simony Lafontaine, Theillet C. – P53 mutation occur in aggressive breast cancer – Cancer Res.
1992-52 – 3918-3923
Overall
37
P53 – Potential Biomarker
■ Prevention
■ Earlier detection of tumor
■ Prognostic
■ Respond to treatment and re-establish chemo-sensitivity
■ Anticipate cancer recurrence
Haupts S., Haupts Y. (2004) – Improving cancer therapy through P53 management: cell cycle: 3 – 912 - 916
P53 and Chemotherapy
P53 mutation Chemotherapy Prognosis ?P53 mutation increases the resistance of cancer cells to numerous
chemotherapeutic agents that damage but not destroy cancer cells. Cancer
cells accumulate and invade other tissues. Only a small fraction of cancer
cells are destroyed.
Eric Wattel, Claude Preudhomme et al… - P53 mutations are associated with resistance to chemotherapy and short survival in
hematologic malignancies – Blood Vol.84 – N.9 – Nov.11 – (1994) 3148 – 3157.
Aas T., Borresen A.L., Geisler S., Smith, Sorensen B, Johansen H. – Specific P53 mutations are associate with de novo resistance to
doxorubicin in breast cancer patients – Nature Medicine 2811-814 38
39
P53 – Potential Biomarker
Urgent Need for New Options
• Earlier detection
• New diagnostic
• Design a personalized treatment adapted to an individual person
• Better response to standard treatment, synergic effects with anticancer
drugs
• Less adverse effects
• New options in treating cancer with natural bioactive agents
Tito Fojo and Susan Bates – Strategies for reversing drug resistance oncogene (2003) 7512-7523
We Need to Overcome the Toxicity of Anticancer
Agents, Radiotherapy, etc.
Toxic toHealthy Cells
41
Dietary Agents with Anti-Cancer Properties
Keith R. Martin – Targeting apoptosis with dietary bioactive agents: Nutrition and cancer Lab., Dept of Sciences – Pennsylvania State Uni – USA - 200642
What Common Foods May kill Multi-Resistant Cancer Cells?
Green-Medinfo
by Dr. J. Mertola
December 5th 2013
Curcumin – Nº 1 cancer fighter
The most effective MDR gene
modulator in combination with
chemotherapy
Inhibit NF.KB (inflammatory
mediator)
Anti-angiogenic
Increase immune cells activity
Increase apoptosis
Anticancer Potential of Curcumin
Bharat B. Aggarwal Ph.D
University of Texas M.D. – Anderson Cancer Center
Houston – Texas - USA43
44
References
• Fazlul H., Sarkar and Yimei Li – using chemopreventive agentes to enhance the efficacy of cancer Therapy –
cancer Res. 2006 66: (7) April 1 – 2006
• Simone Fulda (Children’s Hospital, Ulm. University, Ulmn – Germany) – Modulation of apoptosis by
Natural Products for cancer therapy – Planta Med. 2010:76:1075-1079
• Aggarwal BB., Shisdohia S. – Molecular Targets of dietary agentes for prevention and therapy of cancer –
Biochem Pharmacol 2006 – May 14-71 (10) 1397-421.
• Bharat B., Aggarwal Ph.D. – Anticancer potential of curcumin: An old spice with new targets – Cytokine
Research Section – Dept of Exp Therapeutics – The University of Texas – M.D. Anderson Cancer Center –
Houston – Texas - USA
46
Model for Apoptosis Induction by Cytotoxic DrugsMitochondria Plays the Central Role
Cytotoxic drugs DNA Damage Activation P53
Cell cycle arrest
G1 – G2
Induce permeabilization
of the mitochondrial
membrane
BAX expression
Release of cytochrome C
Activation of caspases
Apoptosis
P53
mutation BCL 2Loss of control
BAX
XIAP
Survivin
Smac Diablo
47
Chemotherapy + Radiation + Dietary agents
Synergy to increase
effectiveness of anticancer
agents
Decrease adverse toxic
effects
Chemotherapy
Radiation
Non selective
Adverse toxic effects
Cisplatin
Doxorubicin
Docetaxel, etc. Induce
Apoptosis
Quercitin
Curcumin
Genistan
Well tolerated
by the body
Dietary agents
Resveratrol
Pomegranate
Inhibit NF.KB
Selective
Non-toxicity
Apoptosis
Chendil D. et al – Oncogene 2004: 26: 1599 - 607
Why Dietary Agents?
Modulation of Apoptosis by Active Dietary Compounds for Cancer Therapy
Curcumin Lung, pancreas, colon, prostate,
stomach, breast.
Increase chemotherapy sensitivity-
synergetic
Gemcitabline, oxilaplatin,
paclitaxel
5 Fu
P53 – P21 – Survivin – NF.KB –
Cox2 – VEGF – BAX – BCL-2
Resveratrol
Apigenin
Ovarian, breast, prostate, liver,
lung, uterine.
Cisplatin, doxorubicin, platinum
compounds, 5 Fu, paclitaxel
Pancreatic cancer
5Fu, Paclitaxel
P53 – BAX – Caspases activator –
P21 – Survivin – BCL-2 – Cyclin 1 –
Cox2
G1-G2 – S-phase arrest
P53 – P21 – BCL-2 – BAX –
Caspases – C-Myc – VEGF –
induce G 2/ M – Cell cycle arrest
Pomegranate
Indole-3 - Carbinol
Prostate, breast, lung, colon, oral,
leukemia
Breast cancer, prostate, pancreatic
Gemcitabine – cisplatin - paclitaxel
BCL-2 – BAX – VEGF – Cox2 – P21
– BAK – NF.KB
BCL2 – BAX – NF.KB
Activate caspases
Organ Site Molecular Target
Green tea
Polyphenols and EGCG
Lung, oral, stomach, liver,
pancreas, colon, bladder, prostate,
breast.
Tamoxifen – cisplatin –
adriamycin, dacarbazine
P53 – P21 – BAX – BCL-2 – NF.KB
– Cyclin 1 - Cox2 – VEGF _
increase Xiap
Isithiocyanates (ITC’s)
Sulforaphane
(Cruciferous vegetables)
Prostate, breast
Docetaxel
Adriamycin
Cisplatin
BCL-2 – Survivin – NF.KB – Cyclin
1 – P53 – caspase activation
Licopene Prostate, lung, breast, gastric,
liver, pancreas colorectal
Adriamycin
Cisplatin
Cyclin D1 - BCL-2 – BCL-4 AKT –
NF.KB – MMP9
Organ Site Molecular Target
Modulation of Apoptosis by Active Dietary Compounds for Cancer Therapy
Ellagic acid Neuroblastoma, pancreas, breast,
prostate, colon, intestine, bladder,
oral, liver.
Cisplatin, vinorelbine
P53 – P21 – Cyclin 1 – Cox 2 –
NF.KB
Increase caspase 3
Quercitin
Capsaicin
Colon cancer, breast.
5Fu, Cisplatin
Doxorubicin
BAX – BCL-2 – Caspase - Cyclin
D1 – Gadd 45
BCL-2 – BAX - Survivin – Cyclin D1
NF-KB – CDK1 – CDK2
Increase Cyt C. release Caspase 3
P53 – BCL-2 – P21
VEGF – Cyclin D1
Catechin 5 Fu, Gemcitabine – mitocycin
Organ Site Molecular Target
Modulation of Apoptosis by Active Dietary Compounds for Cancer Therapy
Anticancer Properties of FoodsApoptosis – Angiogenesis – Inflammation – Immune Defense
“Let food your medicine and medicine be your food.”
Hyppocrates 460-370 B.C.51
52
Celery, Artichokes, Oregano, Parsley Kill Human Pancreatic
Cancer Cells
■ Contain apigenin, luteolin, flavonoids
■ Apigenin alone induced cells death with two aggressive human pancreatic cancers
■ The percentage of cells undergoing apoptosis went from 8.4 percent in cells that had not been
treated with the flavonoid to 43.8 percent in cells that had been treated with no chemotherapy
■ Apigenin inhibited the enzyme glycogen synthase kinase-3 beta (which decrease in the
production of anti-apoptotic genes and increased apoptosis.
■ Pre-treated cells with Apigenin prior to applied chemotherapy received the best result.
Elvira de Mejia, professor of food chemistry and Jodee Johnson – University of Illinois – Published – Molecular nutrition and food research
53
Each Cancer Patient is Different
■ Therefore each cancer patient requires a
personalized diagnostic and treatment
according to individual Molecular Markers
protein assay.
■ Cancer patients with the same
diagnostics have radically different genes
and different pro-apoptotic and anti-
apoptotic proteins from different gene
expression.
West M., Ginsburg, GS, Huang, A.T. Nexins J.R. – Embrassing the complexity of genomic data for personalized medicine – Genome Res. 16, 559-566 – 2006
Serge Jurasunas – Clinical application of molecular markers, prevention, diagnostics in cancer- 2nd Int.Conference on Complementary Oncology – June
2012 – Munich - Germany
Laboratory Blood Analysis: Potential Applications with Cancer patients
Method: Elisa Assay
Quantitative Polymer Chain Reactional
(P.C.R.) 54
• Provide information relevant to normal or abnormal P53 gene expression,
normal P53 protein or mutated protein.
• Provide information relevant to normal or abnormal pro-apoptic or anti-
apoptotic genes.
• It offers clinical diagnostic, prognostic and follow up of the treatment. It
permits us to tailor a personalized treatment.
P53 Gene Expression P53 Protein Level
18.788 copies/µl of plasma 57.3 µ of normal protein/µl of plasma
Reference range
50 copies/µl of plasma
F – 44 Year Old – Non Cancerous Patient –
2009 (Stressed Cells)
Reference range
0.33 units/µl of plasma
Comment:
There is a population of stressed cells with damaged DNA as indicated by P53 gene expression
and a high level of WT protein.
Cancer lesions are unlikely because of the absence of mutated P53 protein .
The cancer defense is functioning.
P53 Assay
55
P53 Gene Expression
P53 Protein Level mutated
P53 Protein Level normal
Not detectable
10.88 units/µl of plasma
Not detectable
340 units/µl of plasma
Reference range:
10-50 units/µl of plasma
Reference range:
0,33 units/µl of plasma
Reference range:
10 units
Reference range:
10-100 units
Survivin Gene Expression
BCL2 Gene Expression
BAX Gene Expression
Not detectable
Patient M – 81 years old – Recurrence of Colon Cancer
- Liver Metastasis 1st Test: 9/3/2011 2nd Test: 11/8/2011
P53 Gene Expression
1.180 units/ml of plasma
P53 Protein Level nnormal
Not detectable
P53 Protein Level mutated
Not detectable
BCL2 Gene Expression
Not detectable
Not detectable
BAX Gene Expression
409 units/ml of plasma
apoptosis
Survivin Gene Expression
129 units/µl of plasma
P21 Gene Expression
Not detectable
P21 Gene Expression
Not detectable
Reference range:
10 units
Reference range:
10-50 units
2 pools of
resistance
56
Patient M. – 44 Years Old – Clinical Story: Multiple Cancer Recurrence – Bladder – Lung – Adrenal
Surgeries – Radiation – Chemotherapy
1st test
18th February 2009
P53 protein level
26.1 u of abnormal protein/µl of
plasma
Reference: 0.33 units/µl of plasma
P53 gene expression
268 copies/µl of plasma
Reference: 1.000 copies/ml of plasma
Mutant protein unable to trigger
the self-destruction of cancer cells
escaping from apoptosis
Chemotherapy ineffective.
2nd test
2nd June 2009
P53 protein level
16.8 u of normal protein/µl of
plasma
P53 gene expression
8.9 x 108 copies/µl of plasma
(100.000 copies)
The treatment reversed the
oncogenic dominance of the P53
to a wild type P53 tumor
suppressor.
Activation of the P53 gene and
normal protein.
Self destruction of cancer cells
3rd Test
7th October 2009
P53 protein level
156 u of normal protein/µl of
plasma
P53 gene expression
1.5 x 1010 copies/µl of plasma
Very high increasing level of
P53 protein.
The applied treatment
continues to have a profound
destructive effect on the
population of abnormal
cancer cells
Treatment to Restore Normal Function of mutated P53 with PSJ53 Therapy (1)
(1) Serge Jurasunas N.D. M.D. (Hom), Olga Galkina Taylor Ph.D. – How to target mutante P53 in a case of multiple cancer recurrence – Townsend Letter
August/Sept 2010 68-72
57
58
F. Breast Cancer Remission: Age 51 Years – High Risk of Recurrence - 2012
Date: 5/11/2010
P53 gene expression
169u/µl of plasma
Reference range: (10-50u)
P53 normal protein level
10.99u/µl of plasma
Reference range: (0.33 units)
Date: 10/08/2010
P53 gene expression
Not detectable
P53 protein level
wild: not detectable
mutated: 33.9 units/ml of plasma
Live Blood Analysis – Infected Ground
THE ANTI-TUMOUR EFFECTS OF THE APPLIED TREATMENT
02/2012 - 12370 05/2012 - 12461 04/2013Ref. Range
P53 gene expression 200 427 874 10-50 units/µl of plasma
P53 level mutated ND ND ND ND units/µl of plasma
P53 level wild ND 0,4 ND 0.10-1.00 units/µl of plasma
Bcl-2 gene expression 8000 796 260 <10 units/µl of plasma
Bax gene expression 167 1543 202 10-100 units/µl of plasma
Bcl-2/Bax ratio 0.02 1.93 0.8
Survivin gene expression 171 900 101 <10 units/µl of plasma
P21 gene expression 139 738 738 10-50 units/µl of plasma
Survivin/p21 ratio 0.8 0.8
VegF gene expression 2353 ND 10-100 units/µl of plasma
A Complementary Approach to Breast Cancer: A Case with Multiple Liver Metastases is
Free from Disease Complete Report – Townsend Letter Magazine – August/Sept 2014
59
Patient F. with a 4 Year Complete Remission
of Pancreatic Cancer (Townsend Letter – August/Sept 2009 USA)
P53 Test
1st Test – 4.5.2009
P53 Gene Expression
65.000 copies/µl of plasma
Reference range: 1000 copies
P53 Protein Level
4.5 µ of abnormal (mutated)
protein/µl of plasma
P53 Wild Type
Indetectable
Reference range: 0.33 copies
2nd Test – 4.8.2009
P53 Gene Expression
8.9 x 108 copies/µl of plasma
Reference range: 1000 copies
P53 Protein Level
1.5 µ of normal protein/µl of
plasma
Reference range: 0.33 copies
We reversed mutant P53 to a
wild type but the actived gene
produced normal P53 protein
only to some extent. Cancer
cells are not fully self-
destroyed
3rd Test – 17.11.2009
P53 Gene Expression
1.2 x 106 copies/µl of plasma
Reference range: 1000 copies
P53 Protein Level
67.4 µ of normal protein/µl of
plasma
Reference range: 0.33 copies
Now the P53 gene is still active
and produces high a level of
P53 normal protein leading to
increased self-destruction of
cancer cells.
Tumor regression can be
anticipated60
61
Description Intracellular Extracellular Comments
P53 gene expression
Reference: 10-50 units/µl of plasma
1.327 units
µl of plasma
43
Anti-tumor activity
P53 level mutated protein ND
P53 level normal proteinReference: 0.10-1.00 units/µl of plasma 6 units 25.2
Bcl-2 gene expression
Reference: 10 units/µl of plasma
487 866 Increasing cancer cells with BCL-2
Bax gene expression
Reference: 10 units/µl of plasma
1.431 411
Anti-tumor activity
Bax/Bcl-2 ratio 2.9
Survivin gene expression
Reference: 10 units/µl of plasma
1.752 167 Dominance
Risk of recurrence
P21 gene expression
Reference: 10 units/µl of plasma
484 952
Survivin/p21 ratio 0.3 Many cancer cells with BCL-2and Survivin are
destroyed over their accumulation
1) Patient – M- 57 Years Old – Tumors of the Bladder, Urethra, Prostate (2011)
No Surgery - Chemotherapy
Complete Remission (Recurrence risk)2014
62
Description Intracellular Extracellular Comments
P53 gene expression
Reference: 10-50 units/µl of plasma
138 units
ul of plasma
419
Many cancer cells destroyed
P53 level mutated protein ND
P53 level normal protein
Reference: 0.10-1.00 units/µl of plasma
ND ND
Bcl-2 gene expression
Reference: 10 units/µl of plasma
176 1066 Before 487
Bax gene expression
Reference: 10 units/µl of plasma
179 2.272
Many cancer cells destroyed
Bax/Bcl-2 ratio 1,0
Survivin gene expression
Reference: 10 units µl of plasma
171 292 Before 1.752 units
P21 gene expression
Reference: 10 units/µl of plasma
167 ND
Survivin/p21 ratio 0.9 Many cancer cells with BCL-2and Survivin are
destroyed over their accumulation
TM2.PK
Reference range: 05-15 units
17.4
Anti-tumour dominance
2) Patient – M- 57 Years Old – Tumors of the Bladder, Urethra, Prostate (2011)
No Surgery - Chemotherapy
Complete Remission (Recurrence risk)June 2015
63
Description Intracellular Extracellular Comments
P53 gene expression
Reference: 10-50 units/µl of plasma
1.196 units
ul of plasma
1.754
Anti-tumor activity
P53 level mutated protein ND
P53 level normal protein
Reference: 0.10-1.00 units/µl of plasma
5.7 ND
Bcl-2 gene expression
Reference: 10 units/µl of plasma
353 2.293 Many abnormal/cancerous cells destroyed
Bax gene expression
Reference: 10 units/µl of plasma
ND 536
Bax/Bcl-2 ratio
Survivin gene expression
Reference: 10 units µl of plasma
ND 2.711 Many abnormal/cancerous cells destroyed
P21 gene expression
Reference: 10 units/µl of plasma
ND 430
Survivin/p21 ratio Many cancer cells with BCL-2and Survivin are
destroyed over their accumulation
Anti-tumour dominance
3) Patient – M- 57 Years Old – Tumors of the Bladder, Urethra, Prostate (2011)
No Surgery - Chemotherapy
October 2015
P53 protein level units/ml of
plasma
No
Date of blood
sample
collection
Wild P53 Ref.
Range* <0.33
units/µl of plasma
Mutated P53 Ref. Range N.D.**
P53 gene (wild
expression level Ref. Range * <106
copies/µl of plasma
BCL-2Ref. range 10
units/µl of
plasma
BAXRef.range 10
units/µl of
plasma
SurvivinRef.range 10
units/µl of
plasma
P21Ref. Range 10
units/µl of
plasma
1 6 Jan 2013 0.2 N.D.** 1.344 2.066 1.714 1.734 2.192
2 11
Mar2013
16.4 N.D.** 820 131 N.D.** N.D.** 229
Table 6 – F – 9 years old – Glioma
Postponed Chemotherapy after 3 Surgeries with Poor Results.
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F.41 years – Asympthomatic Prime lesions 18 cm – Secondary Lesions 8
cm
Advanced Gastric Cancer (1)
Combination of Chemotherapy with our Complementary Treatment that Targets Apoptosis,
Angiogenesis, Immune Activity – Anticancer Diet
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P53 Gene Expression
P53 Protein Level mutated
P53 Protein Level normal
58 units/µl of plasma
35,4 units/µl of plasma
1 unit/µl of plasma
72,4 units/µl of plasma
Reference range:
10-50 units/µl of plasma
Reference range:
0,10 – 1,00 units/µl of plasma
Reference range:
5 - 15 units
Tumor Marker 2 – Pyruvate Kinase
TM2.PK
Advanced Gastric Cancer (2) - Results of Blood Analysis
1st Test: 28/04/2015 2nd Test: 26/06/2015
P53 Gene Expression
223 units/µl of plasma
P53 Protein Level nnormal
4 units/µl of plasma
P53 Protein Level mutated
Not detectable
23,8 units/µl of plasma
Tumor Marker 2 – Pyruvate Kinase
TM2.PK
Comment: We significantely increased about 4 times the expression of P53 gene and increased only to a
certain extent normal P53 protein. We reversed the production of mutant protein to a normal wild type.
TM2.PK activity decreased to a almost normal range.
After the applied therapy
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Advanced Gastric Cancer (3)
After 3rd Scan Secondary Nodules Continue to Reduce Their
Size
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Increasing Tumor-Marker 2 – Pyruvate Kinase (TM2.PK) During or
After Treatment Indicates Relapse and/or Metastasis
■ TM2.PK – A enzyme that assists cancer cells in the rapid utilization of
glucose in the presence of oxygen to generate energy
■ Indicates a metabolically activated tumor
■ May indicate necrosis and/or inflammation (necrotic tumor cells)
■ Follow up during tumor therapy to monitor result of treatment
■ TM2.PK levels decreasing during therapy = success of the treatment
Ventruci M. et al – Tumor M2 pyruvate Kinase, a new metabolic marker for pancreatic cancer – Dig. Dis. Sci. 49:
1149-1151 – 2004.
Luftner et al – Tumor M2 – Pyruvate Kinase expression in advanced breast cancer – Anticancer Res.19 – 2599-2601
– 2000.
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Tumor Marker 2 – PK – Concentrations in Stool Samples from
Patients with Colorectal Cancer
Tumor M2-PK concentrations
In EDTA plasma samples
from patients with lung tumors
Correlation between Tumor M2-PK values and staging
Tumor M2-PK measurements in stool and EDTA-plasma samples
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Conclusion: The importance of Molecular Markers Assay
■ Potential application for cancer patients
■ Prevent cancer disease
■ Improving diagnostic and prognostic
■ Do we have resistant cancer cells
■ Monitoring the response to chemotherapy/radiation
■ Anticipated micro-metastases invasion
■ Dominant anti-tumor activity over pro-tumor activity (vice-versa)
■ Prevent disease recurrence
■ New anticancer strategies
■ Personalize anticancer treatment
■ Better quality of life with less toxic adverse effects
More information
• Articles, clinical cases, integrative cancer treatment.
• Breast cancer: Prevention, Detection, Targeting Molecular Markers.
Townsend Letter – August/Sept 2011
• P53-Tumor Suppressor gene: understanding P53 – based
anticancer therapies utilizing dietary agentes.
Townsend Letter August/Sept 2015
• Natural supplementation as support to cancer treatment.
• After remission or cure: What nutritional treatment next – Two
lectures with illustrations.
www.sergejurasunas.com
Email: [email protected]
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Thank You for
Your Attention!
Don’t Let the Cancer Kill You, but rather Kill the Cancer.
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