A Proven

Supportive Therapy
in Cancer Treatment
dr. Rinny Liestyana

Seminar & Workshop OBGIN 2011

POGI Cab. Jawa Barat Wilayah Priangan Timur
April 3, 2011

History : from NOBEL

Laurate
Albert SZENT-GYORGYI Vitamin C
Molecules with high redox potential
Wheat germ quinones

The quinones :
- block cell replication1
- has an immune-stimulatory
effect2

Albert Szent-Gyorgyi MD, PhD

1893-1986
Hungarian scientist & Nobel Prize Winne
in Physiology or Medicine 1937

1. Pethig R, Gascoyne PR, McLaughlin JA, Scent-Gyorgyi A. Interaction of the 2,6-dimethoxysemiquinone and ascorbyl free Radicals with Ehrlich ascites cells: a probe
of cell-surface charge. Proc Nat Acad Sci USA. 1984;81(7):2088-2091
2. Hidvegi M, Raso E, Tomoskozi-Farkas R, et al. MSC, a new benzoquinone-comtaining natural product with antimetastatic Effect. Cancer Biother Radiopharm.
1999;14(4):277-289

red
u
t
c
ufa
zed
n
i
a
d
r
M
a
and
t
s
by
GMP

Production Process

Glycosides
Aqueous extract

Germ
3%

Fermented with
Saccharomyces
cerevisiae
Glycosidase
18 hours, 30C

2-methoxy-benzoquinone
(MBQ) &
2,6-dimethoxy-benzoquinone
(DMBQ)
Aglycones
Dried extract standardized

Triticum
vulgaris

Mechanism of Action

Cell line (in vitro) studies

Jurkat T-cell leukemia cells
Very strong, dose dependent apoptosis induction

Breast cancer cell lines (estrogen positive AND

negative)
Apoptosis, enhanced the efficacy of Tamoxifen

Colon cancer (HT 29) cells

Apoptosis and necrosis

Neuroblastoma, testicular cancer and ovarian

cancer (ESMO 2010)
Strong synergistic effects with oxaliplatine, 5-FU,
CPT-11 (irinotecan)

Apoptosis-Promoting
Mechanism

Comin-Anduix B, et al. Fermented wheat grem extract inhibits glycolysis/ pensose cycle enzymes and induces apoptosis through poly (ADP-ribose) polymerase activation in
JurkatT-cell leukemiatumor cells. J Biol Chem. 2002 Nov 29;277(48):46408-14. E-pub 2002 Sep 25

Mechanisms behind Apoptosis

Induction
Cell proliferation stops in G 0-G1 phase in cancer cells
No apoptosis induction in normal cells (mononuclear cells)
Through a caspase-based mechanism, cleaving Poly ADPRibose Polymerase (PARP), no DNA repair

Metabolic effects of
AVEMAR
Cancer cells have different biochemistry...
glucolysis

Energy (ATP)

Glucose
phosphate pathway
pathway
Pentose phosphate
Pentose
(PPP)
(PPP)

NADP

Fatty acid
Ribose
(DNA (DNA
synthesis)
Ribose
synthesis)

NADPH

More than 80% of cancer ribose comes from PPP!!!

Metabolic effects of
AVEMAR
1. Inhibits glucose uptake of cancer cells
2. Blocks the non oxydative part of PPP
ribose synthesis

no

1
glucolysis

Energy (ATP)

Glucose
Pentose phosphate pathway
(PPP)

NADP

NADPH

Fatty acid
Ribose (DNA synthesis)
2

Effects of AVEMAR on
cancer DNA metabolism

In vivo (animal) studies

Rat colon carcinogenesis (azomethane) model
(Zalatnai et al 2002)
Azomethane group cancer formation 83%
Avemar group cancer formation 45%

Lewis lung cc, colon cc, colon xenograft, B 16

melanoma model profound metastasis inhibition
Skin graft model Avemar induces blastic
proliferation of T cells
COX 1 and 2 non selective inhibitor
immunomodulation

AVEMAR has an effect on the immune

system...

Immunomodulation
Very significant cytokin production is
induced by Avemar
- TNF- immunity, inflammation, apoptosis
Interleukin production (IL-, IL-, IL-, IL-6, IL-8)

ICAM-1 (Intercellular Adhesion Molecule class 1)

Downregulated on surface of tumor vessels
no help for leucocytic infiltration
Avemar upregulates ICAM-1 expression
making leucocytic infiltration easier

Telekes A, Kiss-Toth E, Nagy T, Qwarnstrom EE, Kusz E, Polgar T, Resetar A, Dower SK, Dudo E. Synergistic effect of Avemar on pro-inflammatory Cytokine production and
ras-mediated cell activation. Ann NY Acad Sci. 2005:1051:515-528

Immunomodulation
MHCI-I (Major Histocompatibility
class I)
Avemar induces a decrease in MHC-I
proteins on the surface of tumor cells,
making the cancer cells vulnerable to Natural
Killer cell activity

Fajka-Boja R, Hidvegi M, Shoenfeld Y, Ion G, Demydenko D, Tomoskozi-Farkas R, Vizler CS, Telekes A, Resetar A, Monostori. Fermented wheat germ extract induces
apoptosis and downregulation on major histocompatibility complex class I proteins in Tumor T- and B-cell lines.Int J. Oncol. 2002;20:563-570

Clinical studies
AVEMAR significantly reduces
the progression-related
events
AVEMAR significantly improves
PFS (progression-free
survival) & OS (overall
survival)
AVEMAR significantly reduces
the events of chemotherapyinduced febrile neutropenia
AVEMAR significantly reduces
free oxygen radicals level
correlated with the improvement
in the quality of life

Indication
Supportive therapy

Regardless of
the type & stadium
cancer

22

Clinical Benefits
AVEMAR extends progression free

time and reduces the number of

progression events
AVEMAR has profound antimetastatic

effect
AVEMAR enhances the effects of

chemotherapy and reduces their side

effects
AVEMAR improves quality of life
23

Contraindication &
Precaution
1. Patients undergoing organ or tissue
transplantation
2. Pregnancy and breastfeeding
3. Patients suffering from bleeding erosions and/
or ulcers of The GI tract , enteritis/ colitis, or
malabsorption syndrome.
4. Gluten sensitive enteropathies (celiac
sprue)
5. Patients with inherited fructose intolerance or
hypersensitivity to any of the components
and ingredients of the product
6. Do not recommended for children
24

Safety
Acute, subacute toxicology tests (GLP) show
minimal side effects
No significant side effects has been
reported, but mild & transient
Wide therapeutic window, toxic dose is 50
times higher than recommended daily dose
FDA : Status GRAS (Generally Recognized
As Safe)

Johanning GL, et al. Efficacy of a medical nutriment in the treatment of cancer. Altern Ther 13(2): 56-63. 2007

26

Dosage & Administration

AVEMAR should be taken once to twice a day,
one box per month
AVEMAR should be taken continuously during &
after the completion of clinical treatments.
AVEMAR should be taken at least 2 hours before or
after meal, any other drugs, supplements, vitamins, &
minerals
AVEMAR should be solved in cold water, non-carbonated
mineral water, providing that their vitamin C or
vitamin E content is not significant.

27

More Than Just An

IMMUNOMODULATOR
Avemar has supported by scientific evidences related
to in vitro, in vivo & clinical studies for
BOTH its anti tumoral & immunomodulatory effect
Avemar significantly reduces the progression-related
events & improves survival rate
Avemar has synergetic effect with cancer therapy &
improves QOL for cancer patients both during chemo- and
radiotherpy and in end-stage disease (anti-cachectic
effect)
Avemar is safe, without major of side effects
Avemar has many mechanism actions as a supportive
therapy in cancer regardless of the type and stage

A PROVEN Supportive Therapy

In Cancer Management

Manufactured & Lisenced by :

BIROPHARMA (Oncology)
Hungary