Combination Combination of Fermented Soyof Fermented Soy with Chemo-Therapy with Chemo-Therapy

-Results of a Phase I Study --Results of a Phase I Study - Dr. Ursula Jacobs Dr. Ursula Jacobs

Klinik am Alpenpark Klinik am Alpenpark D-83707 Ringsee am TegernseeD-83707 Ringsee am Tegernsee

Germany Germany

PD Dr.Dr. Uwe D Rohr PD Dr.Dr. Uwe D Rohr

MED19 Medical CenterMED19 Medical CenterWien-GrinzingWien-Grinzing

Austria Austria

Vienna Dec. 7th 2007

Soy suppresses Soy suppresses Inflammation and CancerInflammation and Cancer

MAPK

NFkB

IL-6 APOPTOSIS

Soy-Isoflavones

Inflammation Cancer

MAPK

NFkB

IL-6 APOPTOSIS

Cancer

Inflammation Cancer CachexiaDepression Imhof et al, 2006

Haegemans et al, 2006Sartyr et al, 2007

MAPK

NFkB

IL-6 APOPTOSIS

Soy-Isoflavone

Inflammation Cancer

MAPK

NFkB

IL-6 APOPTOSIS

Cancer

Inflammation Cancer CachexiaDepression

Chemo-Therapy

Chemo-Therapy Chemo-Therapy increases Inflammation and Reduces Apoptosis increases Inflammation and Reduces Apoptosis

Imhof et al, 2006Haegemans et al, 2006Sartyr et al, 2007

MAPK

NFkB

IL-6 APOPTOSIS

Inflammation Cancer CachexiaDepression

Patient-CharacteristicsPatient-Characteristics

CancerCancer BreastBreast ProstateProstate OvarOvarNumberNumber 88 55 33

Age ( Years)Age ( Years)Min-Max(Years)Min-Max(Years)

585844 - 6644 - 66

585848 - 6348 - 63

5252

DiagnosisDiagnosisPrimary TumorPrimary Tumor(Years)(Years)Min-Max (Years)Min-Max (Years)

8,18,1

4,1 - 12.1 4,1 - 12.1

6,96,9

4,7 - 8,34,7 - 8,3

22

11

Patient with Patient with MetastasisMetastasis

6 out of 86 out of 8 4 out 54 out 5 --

Chemo.Chemo.TherapyTherapy(Years)(Years)Min-Max (Years)Min-Max (Years)

22

1,1 - 3,21,1 - 3,2

2,22,2

--

2,32,3

2-2,82-2,8

Tumor Breast Prostate Ovary

n = number of participants

8 5 3

ER-ß ?

ER- + + +

Her-2-Rec. - -

Apoptose

p21

VEGF - - -

Anti-angiogenese

+ + +

Phase I Study*

Summary of Molecular Results Summary of Molecular Results Combination-Therapy Combination-Therapy

Fermented Soy Fermented Soy ++ Chemo-Therapy Chemo-Therapy * 3Month Therapy

Rohr , et al 2007 , unpublished results

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Inhibition of Cell Cycle

IsoflavoneTamoxifen

Fermented Soy and ER-ß Expression in dissimated cells

n=5

ER-ßER-ß300

200

100

0 Zeit (Monate)

0 1,5 3

Patient consume Isoflavones regularly Patients with high GLEASON Factor(High Malignicy)

facher Anstieg

PSA-ValuePSA-Value300

200

100

0

Zeit (Monate)

0 1,5 3

Fermented Soy and Classical Cancer Parameter

Forschung und Praxis 435; 2006 S 16

Cachexia is the leading death among cancer patients

Cachexia:

Part of Aging Process Chronic Inflammatory Aging Diseases and Cancer: Chronic Inflammatory Aging Diseases and Cancer:

Estrogen-Receptor-Beta (ER-ß) Estrogen-Receptor-Beta (ER-ß) DeficienciesDeficiencies

ER-ß

Inflammation(IL-6, TNF-...)

Cancer

suppresses suppresses

Arteriosclerosis, Blood Pressure, Dementia, Osteoporosis, Cystitis , etc.

Cachexia

Cytocines cause CachexiaCytocines cause Cachexia

Morley et al Morley et al Am J Clin Nutr Am J Clin Nutr 2006;83:735– 432006;83:735– 43

Inflammation Marker TNF-Inflammation Marker TNF- can be reduced by Soy - Isoflavones can be reduced by Soy - Isoflavones

120 mg Genistein / day

n=16 postmenopausa women

Rohr , et al 2007 Times (Weeks)

Base line Isoflavone consumption after consumtion

Tumor Brust Prostata Ovar

n = Patienten 8 5 3

Reduction of Cachexia

+ + +

Increase of Apoptosis

+ + +

Phase I Study*

Cachexia and Apoptosis Cachexia and Apoptosis

Combination (Fermented Soy Combination (Fermented Soy ++ Chemo-Therapy) Chemo-Therapy)

* 3Month Therapy

Rohr , et al 2007 , unpublished data

Appetite Increaseby fermented Soy during Chemotherapy

in Breast Cancer Patients

13. Have you lacked appetite?

13. Have you lacked appetite?

Please answer all of the questions yourself by circling the number that best applies to you

Not at All

Little a Bit

Quite Very much

after 3 Month

EORTC QLQ-C30 (Version1)

Rohr , et al 2007 , nicht veröffentichte Ergebnisse

Body Weight Increase by fermented Soy and Chemotherapy

Mamma Ca

130

120

110

100

130

120

110

100

Body Weight Increase(%)

130

120

110

100

130

120

110

100

Body Weight Increase(%)

Prostate Ca

EORTC QLQ-C30 (Version1)

Rohr , et al 2007 , nicht veröffentichte Ergebnisse

130

120

110

100

130

120

110

100

Body Weight Increase(%)

Ovarian Ca

after 3 Month

Soy-Isoflavone do not act like Soy-Isoflavone do not act like Estrogens !!!Estrogens !!!

Cerebral hemisphäre :ER-ß Rezeptoren

cognition

Hypothalamus : ER-ß und Testosteron Rezeptoren

Ängstlichkeit, Depression, Stress, Stress, PMS, ADD/ADHD, Hormone Regulation & mehr

Stress reduction silences Immune-System

Stress accompanies Cancer

Psychotropic-Effects of Fermented Soyin Cancer Therapy

(with Chemo-Therapy) documented by a standardized Questionaire

EORTC QLQ-C30 (Version1)

23. Were you stressed ?

24. were you depressed ?

24. were you depressed ?

Uwe Rohr, unreported results, 2007

23. Were you stressed ?

Please answer all of the questions yourself by circling the number that best applies to you

Not at All

Little a Bit

Quite Very much

after 3 Month

after 3 Month

Mamma Ca

Mamma Ca

25. Did you have difficulties either memorize things or finding words ?

25. Did you have difficulties either memorize things or finding words ?

Please answer all of the questions yourself by circling the number that best applies to you

Not at All

Little a Bit

Quite Very much

Psychotropic-Effects of Fermented Soyin Cancer Therapy

(with Chemo-Therapy) documented by a standardized Questionaire

EORTC QLQ-C30 (Version1)

after 3 Month

Uwe Rohr, unreported results, 2007

ER-ß , ER-ß , ER-ER-

CNSER-ER-ß

ArteriesER-ß

Mamma ER-ER-ß

BladderER-ß

UterusER-

Ovaries ER-ER-ß

Bones ER-ER-ß

LungER-ER-ß

LiverER-

ColonER-ßER-

ProstateER-ER-ß

TesticlesER-ER-ß

Uwe D Rohr , GYNE 2006

-Cystitis (3 cases in breast cancer cases) -Cystitis (3 cases in breast cancer cases) -sleep improvement (8 x = 75 % of all -sleep improvement (8 x = 75 % of all participants) participants) -no poll allergy (5 cases) -no poll allergy (5 cases) -improved cognition (75%) -improved cognition (75%)

Joint painJoint pain-no pain in finger joints (2x)-no pain in finger joints (2x)-no backpain (1x) -no backpain (1x)

General observation in man and womenGeneral observation in man and women-Improved skin appearances -Improved skin appearances -improved nails and hairs -improved nails and hairs

Improvement of ER-ß related Diseases by Improvement of ER-ß related Diseases by fermented Soyfermented Soy

(Not including (Not including psychotropicpsychotropic effects) effects)

Patient U.L Patient U.L

Date of Birth.: 14.5.58

08/03 First Diagnosis: Mamma CA, Primary tumorTumor-Excission, plus Axilla-Dissection

6 x cycles Chemotherapie, 3 x cycles Zoladex 11/3 Liver metastasen, Chemo-Embolisation, Prof. Vogel , Frankfurt 01/05 Leber Metatstasen: komplette Remission of primary tumor

26.07.06 New liver Metastasis

Begin 04/07 HAELAN 951

25.4.2007 2.8.2007 12/07

Tumor-Size Reduction by Tumor-Size Reduction by Fermented SoyFermented Soy

0

5

Liver Tumor -Diameter (cm)

Fermented SoyStrong Mood Improvement

Depression

Fermented Soy Strong Mood Improvement

Patient U.L.Patient U.L.

Uwe Rohr et al, unreported results, 2007

25.4.2007 2.8.2007 12/07

Tumor-Size, Depression, Body-WeightTumor-Size, Depression, Body-Weight

And And fermented Soy fermented Soy

0

5

Liver Tumor -Diameter

(cm)

Fermented SoyFermented Soy

Body Weigth Improvement

(kg)

5kg

10kg

Strong depression

strong mood improvementstrong mood improvement

Uwe Rohr et al , unreported results, 2007

25.4.2007 2.8.2007 12/07

Can Dissiminated Breast Cancer-Cells be reduced by Can Dissiminated Breast Cancer-Cells be reduced by by fermented Soy ?by fermented Soy ?(Cancer Stem-Cells)(Cancer Stem-Cells)

0

5000

Fermented Soy Treatment

Patient SM, 48 Years

Cell Numbers per

(ml) ongoing

Uwe Rohr et al , unreported results, 2007

Fermented Soy

3 month

In blood

Metastasis

Invasive Cacinoma

Cavities

Residual-Tumor

Cavities

Residual-Tumor

Numbers

MalignityIn blood

Invasive Carcinoma

Metastasis

Phase I Study In Vienna

(Schematic description)

Cancer Stem-Cell

Less malignant Cancer Stem Cell

non cancerogenic cancer cell

non cancerogenic cancer cell