Naturopathic Oncology Slideshare316

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

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.

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

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

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



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



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


Not detectable

BCL2 Gene Expression

Not detectable

Not detectable

BAX Gene Expression

409 units/ml of plasma

apoptosis

Survivin Gene Expression


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


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



P53 Protein Level

1.5 µ of normal protein/µl of

plasma


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



P53 Protein Level

67.4 µ of normal protein/µl of

plasma


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


1.431 411

Anti-tumor activity

Bax/Bcl-2 ratio 2.9

Survivin gene expression


1.752 167 Dominance

Risk of recurrence

P21 gene expression


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


P53 gene expression


138 units

ul of plasma

419

Many cancer cells destroyed


P53 level normal protein

Reference: 0.10-1.00 units/µl of plasma

ND ND



176 1066 Before 487

Bax gene expression


179 2.272

Many cancer cells destroyed

Bax/Bcl-2 ratio 1,0


Reference: 10 units µl of plasma

171 292 Before 1.752 units

P21 gene expression


167 ND

Survivin/p21 ratio 0.9 Many cancer cells with BCL-2and Survivin are


TM2.PK

Reference range: 05-15 units

17.4

Anti-tumour dominance



Complete Remission (Recurrence risk)June 2015

63


P53 gene expression


1.196 units

ul of plasma

1.754

Anti-tumor activity


P53 level normal protein

Reference: 0.10-1.00 units/µl of plasma

5.7 ND



353 2.293 Many abnormal/cancerous cells destroyed

Bax gene expression


ND 536

Bax/Bcl-2 ratio


Reference: 10 units µl of plasma

ND 2.711 Many abnormal/cancerous cells destroyed

P21 gene expression


ND 430

Survivin/p21 ratio Many cancer cells with BCL-2and Survivin are


Anti-tumour dominance



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.

64

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

65

P53 Gene Expression


P53 Protein Level normal



1 unit/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


P53 Protein Level nnormal



Not detectable


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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Naturopathic Oncology Slideshare316

Health & Medicine

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