Cancera deadly disease

Cancer Presentation in Pakistan

About 80% of cancer patients in Pakistan are diagnosed with advance disease and treated with conventional mode of treatment.

20% of cancer patients in Pakistan are candidates of radical treatment which includes, Surgery, Radiation, Chemotherapy and Targeted therapies.

Objective: The primary goal of Oncologist is to improve the quality of life and stop disease progression.

Avemar®Avemar Pulvis

Dr. AssadUllahGeneTec (Private) Limited

MBBS.MBA

Avemar® a new StrategyAvemar Pulvis

An Evidence Based Integrative Medicine

Integrative Medicine?Integrative Medicine? What is Integrative Medicine?

Evidence based, scientifically proven, clinically trailed medicine combines conventional care that have been shown to be safe to improve patient care rather than practice one type of medicine, “Integrative Oncologists” will often combine therapies and treatment approaches to ensure the best results for their patients. 

Avemar®, a new strategy A new strategy of supportive therapy in Medical

Oncology means to help drugs to target directly to cancer cells thus, reducing the amount that gets to the normal cells, increasing the drug’s anti-cancer effects and reducing their toxicity. By improving the therapeutic index of cancer drugs, we aim to turn cancer in to chronic, manageable disease.

Another aspect of the new strategy of supportive therapy in Medical Oncology is to help the patient’s natural anti-cancer defense mechanisms to fight proliferation, propagation and dissemination of cancer cells thus, also turning cancer in to a more chronic disease.

HHistory + Discoveryistory + Discovery Albert SZEN-TGYÖRGYI (1893 to 1986) Hungarian/American scientist Noble prize on Vitamin C 1937

Loss of wife (breast cancer) Molecules with high redox potential Wheat germ –kinons- ascorbic acid (2,6 dimethoxy-benzoquinone- DMBQ)

Research continued! http://v.ytapi.com/watch?v=a-xn1INYsoY

Albert Gyorgyi “NFCR” FounderAlbert Gyorgyi “NFCR” Founder

What is AVEMARWhat is AVEMAR®®?? Avemar is a biotechnologically formulated

nontoxic anticancer Fermentation with Saccharomyces cerevisiae

(WGE) Standardized extract for 2,6-dimethoxy-

benzoquinon (DMBQ) Complex mixture – Pulvis Manufacturing according to GMP and

pharmaceuticals standards/EU guidelines

Mechanism of ActionMechanism of Action

Apoptosis InductionApoptosis InductionVia Poly (ADP-ribose) polymerase (PARP)Cell proliferation stops in G0-G1phase in cancer cells

AVEMAR®

Molecular Target of Avemar®

MHC-1 (Major Histo-compatibility Class 1 protein)

Tumors can fool the immune system by disguising themselves as normal cells. They can develop a camouflage by expressing high levels of MHC-I in order to to avoid recognition by the specific cells of the immune system that play an important role in antitumor defense – the so called natural killer (NK) cells. Natural killer cells recognize and are blocked by the expression of MHC-I molecules on their target cells. Avemar reduces the MHC-I level on human tumor cells, it sensitizes them against NK killing, thus reducing their metastatic activities.

Avemar® and MHC-1 Molecule

Avemar® and I-CAM ICAM-1 (Intercellular adhesion molecule-1) In order to defend the body effectively, some cells of the

immune system – the leucocytes – require special molecules to help them get through the walls of the vessels and infiltrate the attacker. One of these special molecules is called the ICAM-1. In the presence of abundant amounts of ICAM-1, leukocytes can get through the walls of the vessels easily. It is known that the inner cells of the vessels of some tumors have smaller amount of ICAM-1 compared to normal cells, and this phenomenon can be considered an escape mechanism because efficient leukocyte infiltration is impaired. It has been shown that Avemar makes more ICAM-1 on the cells of the vessels, thus helping the leucocytes to infiltrate the tumor.

ImmunImmune e modulationmodulation Stimultion of cellular immune response,

immunoblastic transformation AVEMAR® downregulates MHC class I antigens in

cancer cells, thus they are more susceptible for NK (Natural Killer) cell killing

AvemarAvemar®® Immune EffectsImmune Effects AVEMAR® significantly increases TNF-α

productionInduces heamorrhagic necrosis in tumors

Via upregulation of cell adhesion mulecules (ICAM-1) AVEMAR® assists leukocytes infiltrating tumor cells

Non-selective COX inhibition Downregulation of nuclear antibodies.

AvemarAvemar®® and and GlucolysisGlucolysis Cancer cells use glucose - via the pentose phosphate

pathway – for ribose synthesis – the building block of DNA

AVEMAR® decreases the glucose consumption of cancer cells, thus indirectly inhibiting DNA synthesis

AVEMAR® also decreases the de novo DNA synthesis by inhibiting RR (Ribonucleotide reductase)

AVEMAR® normalizes the glucolytic pathways in cancer cells and redistributes glucose for fatty acid synthesis

Avemar® & Glucolysis

Avemar® Prevents Cachexia As per NCI 70% cancer patients suffers from Ca Cachexia.

It is actually a condition called “Cachexia” which typically prove fatal in cancer.

Cancer cells produce a large amount of Lactic Acid as the result of Glycolysis.

Lactic Acid is the same acid that causes muscles to burn after hard workout.

The Liver convert this Lactic Acid, regrettably, back to sugar.

Avemar prevents cancer cells from building enough DNA to multiply as quickly as they need.

Sugar consumption is this reduced and the vicious circle is broken.

Mechanisms of ActionMechanisms of Action AVEMAR® increases cellular and decreases

humoral immune response AVEMAR® normalizes the impaired glucolytic

pathways of cancer cells AVEMAR® inhibits de novo DNA synthesis AVEMAR® induces apoptosis – programmed cell

death AVEMAR® prevents the formation of metastases

Safety of AVEMARSafety of AVEMAR®®

Acute, subacute toxicology tests (GLP) show minimal side effects

Wide therapeutic window: toxic dose is 50 times higher than recommended daily dose

FDA approved (GRAS) Long term studies show no haematologic effects Could be administered during and after

radiotherapy,chemotherapy and surgery. Shortens reconvalence after surgery

Drug InteractionsDrug Interactions Cytostatics:

Increases the efficacy of all tested antioncotic agents

Decreases their side effects and reduces their toxicity

Reduces neutropenic septicemia Interaction with antiestrogens are unknown Could be administered together with cytokines Synergist with Imatinib mesylate (CML) and

antagonizes resistence Ascorbic acid (Vitamin-C) may attenuate the effect

of AVEMAR® - 2 hours interval is necessary between taking the two medicines

Clinical StudiesClinical Studies Anticancer effect:

Colorectal cancer Malignant melanoma Oral cavity cancers Breast cancer Lung cancer Gastric cancer Pediatric cancers Blood Cancer Hepatocellular Cancer Ovarian Cancer

Autoimmune disorders Rheumatoid arthritis SLE

AVEMARAVEMAR® ® in in Ca Ca Colorectal Colorectal 104 104 control patients

3.8% Stage IV Surgery + chemotherapy (5-FU)

66 AVEMAR® patients 27.3% Stage IV Surgery + chemotherapy (5-FU) + Avemar

9 months follow-up End point: tumor progression

Avemar in CRC Avemar in CRC

Double-blind Multicenter Double-blind Multicenter Clinical StudyClinical Study

Avemar in Metastatic Colorectal CancerDepartment of Medical Oncology

Chaim Sheba Medical CenterUniversity of Tel-Aviv

Gastrointestinal Cancers UnitDepartment of Medical Oncology

Ichilov Medical Center University of Tel-Aviv

Kaplan-Meier Survival AnalysisKaplan-Meier Survival AnalysisFWGE in metastatic colorectal cancer FWGE in metastatic colorectal cancer

(double-blind study, Israel)(double-blind study, Israel)

Log Rank Test p=0.04 Survival of the patients in the

Avemar group is significantly longer than that in the placebo group

  Survival Time 95% confidencey interval of the

 

median (months) median of the survival time

Avemar 22.7 17.6-27.9 Placebo 12.4 10.2-14.6

AVEMARAVEMAR® ® in Malignant in Malignant MelanomaMelanoma104 Randomized study, Stage III patients Dacarbazin alone – n=23 Dacarbazine + AVEMAR® - n = 19 End point: progession (events/free)

Time to progression

AVEMARAVEMAR® ® in Head and Neck in Head and Neck CancerCancer

104 N= 45 (44 planocellular, 1 adeno cc) Planocellular Carcinoma: A carcinoma derived from stratified squamous epithelium. It may

also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed).

Results – after 1 yearAVEMAR® Control

Mortality 0/23 1/22 N.S.New recurrence

1 (4,3%) 12 (54,5%) p<0,001

New metastasis

1 (4,3%) 4 (22,7%) N.S.

Progression event

2 (8,7%) 17 (77,3%) p<0,001

AVEMARAVEMAR® ® in Head and Neck in Head and Neck

104 N= 45 (44 planocellular, 1 adeno cc) Results – after 5 years survival

AvemarAvemar® ® adjuvant Breast adjuvant Breast Cancer TreatmentCancer Treatment

Duration of study: 1991-2001 Number of patients: 39 Mean duration of Avemar treatment: 19.3 months Staging of patients at baseline UICC staging no of patients % 1 3 7.7 11 14 35.9 111 09 23.1 1V 13 33.3

AvemarAvemar®® adjuvant Breast adjuvant Breast Cancer TreatmentCancer Treatment

Results: Changes in side effects of chemotherapy due to Avemar treatment.

No. of patients % No changes 15 38.5 Ameliorated 10 25.6 Ceased 14 35.9 Changes in body mass (mean+/- SD) of patients due to

Avemar treatment. Before Avemar Treatment After Avemar Treatment Difference Significance

72.2 +/- 13.9 75.4 +/- 14.6 +5.1+/- 6.1 P<0.001

AvemarAvemar®® in TNBC in TNBC Anticancer activity of FWGE (Avemar) in triple

negative breast cancer. Objective: Avemar has been shown to potentiate induction

of apoptosis by tamoxifen, however its effects in triple negative and Her2 over expressing cells and interaction with chemotherapy have not been investigated until now.

Results: Avemar exhibits highest cytostatic activity against triple negative HCC 38 cells in MTT and colonogenic assays with IC50 values of 180 and 15 Ig/ml, respectively, indicating likely clinical activity. In combination with docetaxel , additive and marginally synergistic effects were demonstrated in triple negative HCC-38 and Her2/neu overexpressing SKBR-3 cells, whereas in the estrogen responsive MCF-7 cell line, cytostatic activity was

AvemarAvemar® ® in TNBC in TNBC antagonized by Avemar. Invasive capacity of breast

cancer cells was inhibited by Avemar in all three cancer cell lines investigated in a dose-independent manner.

Conclusion: Avemar exerts highest anticancer activity against triple negative HCC-38 human breast cancer

Avemar in Ca OvaryAvemar in Ca Ovary Abstract: OBJECTIVE: Most women with advanced-stage epithelial

ovarian cancer (OVCA) ultimately develop chemoresistant recurrent disease. Therefore, a great need to develop new, more active, and less toxic agents and/or to optimize the efficacy of existing agents exists.

METHODS:

In this study, we investigated the activity of Avemar, a natural, nontoxic, fermented wheat germ extract (FWGE), against a range of OVCA cell lines, both alone and in combination with cisplatin chemotherapy and delineated the molecular signaling pathways that underlie FWGE activity at a genome-wide level.

Avemar in Ca OvaryAvemar in Ca Ovary RESULTS:

We found that FWGE exhibited significant antiproliferative effects against 12 human OVCA cell lines and potentiated cisplatin-induced apoptosis. Pearson correlation of FWGE sensitivity and gene expression data identified 2142 genes (false discovery rate < 0.2) representing 27 biologic pathways (P < 0.05) to be significantly associated with FWGE sensitivity. A parallel analysis of genomic data for 59 human cancer cell lines matched to chemosensitivity data for 2,6-dimethoxy-p-benzoquinone, a proposed active component of FWGE, identified representation of 13 pathways common to both FWGE and 2,6-dimethoxy-p-benzoquinone sensitivity.

Avemar in Ca OvaryAvemar in Ca Ovary CONCLUSION:

Our findings confirm the value of FWGE as a natural product with anticancer properties that may also enhance the activity of existing therapeutic agents. Furthermore, our findings provide substantial insights into the molecular basis of FWGE's effect on human cancer.

Avemar in HCC Avemar in HCC Abstract: Hepatocellular carcinoma (HCC) is one of the most common

causes of cancer –related deaths Worldwide. Due to difficulties in early diagnosis, curative treatments are not available for most patients. Palliative treatment such as chemotherapy are often associated with low response rate, strong adverse effects and limited clinical benefits for patients. The alternative approaches such as FWGE with antitumor efficacy may provide improvements in the clinical outcome of current therapy for HCC. This study aim to clarify antitumor efficacy of FWGE and the combination drug effects of FWGE with chemotherapeutic agents, cisplatin and 5-FU in HCC human cells, HepG2, Hep3B and Hepj5 cells. The present study indicated that FWGE exhibited potential to suppress HepG2, Hep3B and HepJ5 cells,

Avemar in HCC Avemar in HCC With the half maximal inhibitory concentration (IC50)

of FWGE were 0.949, 0.371 and 1.524 mg/ml, respectively. FWGE also induced Poly (Adenosine diphosphate ribose) Polymerase (PARP) associated cell death in Hep3B cells. Moreover, the FWGE treatment further enhanced the cytotoxicity of cisplatin in all tested HCC cells, and cytotoxicity of 5-FU in a synergistic manner in HepJ5 cells. Collectively, the results identified the antitumor efficacy of FWGE in HCC cells and suggested that FWGE can be used adjunct to effectively improve the tumor suppression efficacy of cisplatin and 5-FU in HCC.

AVEMARAVEMAR® ® and Qand QoLoL 104 Oral cavity cancer, operated patients (n=

55) AVEMAR® administered for 60 days after

surgery Results:

No change in BMI in AVEMAR® group Significant decrease of BMI in control

group Significant decrease of oxydative stress

level (serum hydroperoxides Significantly improved life quality

(Spitzer QOL index)

Favorable effects of Favorable effects of AVEMARAVEMAR®®

104 No signs of acute, subacute or chronic toxicity, could be administered for years

No major side effects Wide therapeutic window Immune modulation: increasing cellular

and decreasing humoral immun response Normalizing the glucolytic pathways in

cancer cells

Favorable effects of Favorable effects of AVEMARAVEMAR®®

104 AVEMAR® could be used regardless of stage and cancer type

AVEMAR® enhances the effects of chemotherapy and reduces their side effects

AVEMAR® extends progression free time and reduces the number of progression events

AVEMAR® has profound antimetastatic effect

AVEMAR® improves quality of life

Summary Avemar have been investigated extensively Avemar shows direct anti-tumoral effects Avemar induces apoptosis in cancer cells Avemar inhibits de novo DNA synthesis& DNA repair As an Immuno-modulator Boost cellular response Increases cytokine production (TNF-α,IL 6-β) Assist leucocytes infiltrating tumor cells (ICAM) Assist NK cells attaching cancer cells

Summary1. Avemar showed anti-metastatic effects2. Avemar increased the progression free

survival3. Improved overall survival4. Should be used as supportive treatment in

cancer regardless of type and stage5. Safe. Without any major side effects

Taking AVEMARTaking AVEMAR®®

104 AVEMAR® is supplied in sealed sachets. One box containing 30 units – 1 month treatment

AVEMAR® to be dissolved in water and drunk one hour before breakfast

AVEMAR® to be kept cooled (under 15C) at all times

Favourable effects appear after 3 weeks of administration

Oncology Leaders Views

AVEMARAVEMAR®®

from noble prize to…

prized anticancer

AVEMARAVEMAR®®