Mr. LEE Chee Cheow (M.Sc.) Chief Scientific Officer,

International Advanced Bio-Pharmaceutical Industries Pte Ltd.

Promoting the Nutriceutical Science of Preventive Self-care

EffectiveAdjuvant & Complementary Agents

for

Cancer Therapy

Medicinal Fungus

Cancer Etiolopathology

Characteristics of Cancer Cells

The problem:

Cancer cells divide rapidly

(cell cycle is accelerated)

They are “immortal”

Cell-cell communication is altered

Uncontrolled proliferation

Invasiveness

Ability to metastasise

Current major approaches to

Therapy of cancers

Six Established Rx Modalities:

1. Surgery

2. Radiotherapy

3. Chemotherapy

4. Endocrine therapy

5. Immunotherapy

6. Targeted therapy

Current Cancer Treatment

• Rarely is a single agent effective

• Rather, multiple agents and treatment

modalities are used

SYNERGY (Chemo + TCM) Cancer Treatment

is more effective than Chemo or TCM alone

Study CentersTreatment

Group

Patient

size

Median Survival

Time (months)

Lin xx

(8 hospitals)

Synergy

Chemo

TCM

199

215

173

12.03

8.46

10.92

Chou xx

(6 hospitals)

Synergy

Chemo

TCM

103

92

99

11.8

7.9

9.7

Liu & Fan

(10 Hospitals)

Synergy

Chemo

TCM

137

146

74

19.4

14.53

14.02

Results of multi-center, randomized, parallel, controlled, prospective study methods to evaluate the effectiveness and safeness of using

Synergy Medicine treatment in advanced NSCLC patients.

Extract from clinical presentation at SGH on “Demonstration of Synergy Medicine treatment research in advanced non-small

cell lung cancer” by Prof. Liu Jia Xiang & Prof. Fan Zhong Ze , Shanghai University of TCM.

Chemotherapy drugs• They are Anti- proliferative

– i.e. they damage DNA and so initiate apoptosis (programmed cell dead).

• They also affect rapidly dividing normal cells

– e.g. bone marrow, hair follicles, sperm forming cells.

TISSUE TYPE UNDESIRED EFFECTS

Bone marrow Low white blood cell > infection risk

Immunosuppression

Low red blood cell > Anemia

GI tract Oral or intestinal ulceration; Diarrhea

Hair follicles Alopecia (Hair loss)

GonadsMenstrual irregularities, including premature

menarche; impaired spermatogenesis

Wounds Impaired healing

Fetus Teratogenesis (especially during first trimester)

Adverse Drug Reactions (side effects)

of Anti-neoplastic (Chemo) Drugs

Adjuvant & Complementary Cancer TreatmentsGoals:

Helps potentiate the efficacies of existing anti-cancer chemotherapeutical drugs.

Helps eradicate microscopic cancer after surgery

Helps alleviate symptoms and prevents the decline in immunity

Avoidance of life-threatening toxicity

Increased survival and improved quality of life

Medicinal mushrooms

Many Pharmaceuticals are derived from the Fungus Kingdom:

• Penicillin (antibiotic)

• Ciclosporin (immunosuppressant)

• Griseofulvin (antifungal)

• Statins (cholesterol lowering)

• Mushrooms are prebiotic

• They have immune system enhancement properties

• They are anti tumour agents

Mushrooms (Fungus): source of potent natural based Chemopreventive Agents

Anti cancer compound isolated from mushrooms

Compound From Fungus

Antroquinonol Antrodia camphorata

CordycepinCordyceps

(Cordyceps militaris)

Ganoderic acidReishi

(Ganoderma lucidum)

Grifolin Albatrellus confluens

Hispolon Phellinus linteus

Illudin-S Omphalotus illudens

LentinanShiitake

(Lentinula edodes)

Psilocybin Psilocybin mushrooms

Polysaccharide of Coriolus versicolor(Turkey Tail)

Pharmacology:

• Anticarcinogen

• Antiproliferative

• Immunological regulator

A mushroom used in traditional Asian herbal remedies.

GEN PHARMAC 30;1:1--4, 1998. © 1998 Elsevier Science Inc.

Polysaccharide peptide (PSP):

• isolated 1983 in China.

• PSP is currently research in many countries for use as an anti-tumor drug.*

• PSP immunologic activity is hypothesized to be the main underlying mechanism responsible for its antitumor effects as well as its impact on survival rates.

* Phase 1 Clinical Trial of Trametes versicolor in Women with Breast Cancer; International

Scholarly Research Network, ISRN Oncology Volume 2012, Article ID 251632

Polysaccharide K (PSK):

• In 1980s, Japanese government approved the use of PSK for treating several types of cancer.

• PSK is a best-selling anti-cancer drug in Japan, where it is currently used as a cancer treatment along with surgery, chemotherapy, and radiation therapy.

Two substances extracted from the mushroom:

Polysaccharide-peptide (PSP) of

Coriolus versicolor

Pharmacological Actions：control the growth of tumour cells

• lung cancer • stomach cancer • lymphoma • leukemia• sarcoma-180

Clinical applications:

• Adjuvant to chemo & radiation therapy

• Significantly improved immunity of immune

suppressed patients during treatment, reduce

toxicity caused by chemotherapy.

• Relieve symptoms of: fatigue, nausea, vomiting,

dry mouth, anxiety, cold sweating.

• Improve appetite, relieve pain, improve sleep

quality, improve overall quality of life of patients

during treatment.

• PSP activates monocytes in resting human peripheral blood mononuclear cells: Immunomodulatory implications for cancer treatment; Food Chemistry, Volume 138, Issue 4, 15 June 2013, Pages 2201-2209

• A review of research on the protein-bound polysaccharide (polysaccharopeptide, PSP) from the mushroom Coriolusversicolor Review Article; General Pharmacology: The Vascular System, Volume 30, Issue 1, January 1998, Pages 1-4

Phellinus linteus

• Medicinal mushroom Phellinus linteus

(Berk. et Curt.) has been used in traditional

oriental medicine in Japan, China & Korea.

• Study in Japan demonstrated that PL has

strongest anti tumor effects compared to

other mushrooms.

Anti tumor Biological activities

• ANGIOGENESIS

• APOPTOSIS

• CHEMOPREVENTION

• Anti INVASIVE

• Anti PROLIFERATION

Other pharmacological effects:

• immunomodulatory

• anti-inflammatory

• anti-allergic

• anti-oxidant

Anticancer Effect of Phellinus linteus ; Potential Clinical Application in Treating Pancreatic Ductal Adenocarcinoma; Kang et al., J Carcinogene Mutagene 2013, S9

Phellinus linteus

Breast-Mate®, whose major component is an extract from P. linteus which has exhibited ant proliferative, anti-invasive and anti-angiogenic activities against

Medicinal mushroom Phellinus linteus as an alternative cancer therapy (Review); Experimental and therapeutic medicine 1: 407-411, 2010

Antrodia Camphorata: A Rare Fungus

World’s most valuable medicinal fungus compared:

Bio-Active Ingredients Ganoderma Lucidium Antrodia Camphorata

Bio Active Triterpenes 20-50 types >200 types

Triterpenes concentration 1 – 3 % 10-45 %

AC is highly priced for its effectiveness in treating

the following ailments over centuries in Taiwan:

• Anti-cancer

• Improve liver functions

• Anti Fatigue

• Anti-inflammation

• Anti-hepatitis infection

• Improve immunity

• Anti-allergenic

Product Information :

IMMUNO CPX: A cancer therapeutic formulation

developed by 2 Taiwan medical University in

collaboration with Japan genetic research

institute, base on immunotherapy approach.

Indication:

• Used as a immunotherapy adjuvant to cancer treatment along

with surgery, chemotherapy and radiation therapy.

• Helps to potentiate the efficacies of existing anti-cancer

chemotherapeutical drugs.

• Helps alleviate symptoms and prevents the decline in immunity.

INGREDIENT:

• Antrodia camphorata mycelium

• Phellinus linteus mycelium

• Coriolus versicolor polysaccharide

• Extractum curcumae longae

Immunotherapy: A New Anticancer Approach Also called biological therapy, immunotherapy aims to

boost a person's immune system to fight disease.

Clinical application:

KEY FEATURES:

High Safety

No Resistant for Liver Cancer and others

cancer therapies from non-option patient

experience

• USFDA Patent 7342137 Mar.11,2008

• USFDA Patent 7385088 Jun.10,2008

• USFDA Patent 7411003 Aug.12,2008

• USFDA Patent 7456225 Nov.25,2008

• USFDA Patent 7501454 Mar.10,2009

• USFDA Patent 7468392 Dec.23.2008

Antroquinonol®

High safety

High performance

Anti cancer compound

Based on Human Cancer Cell, Antroquinonol® can Assist the Treatment of Multiple Therapies in Solid Tumor.

New Anti Cancer CompoundIsolated from Antrodia Camphorata

OH

O

O

O 1

2

34

5

6

22

7

89

21

10

11

12

13

20

14

15

16

17

18

19

23

24

Safety:Orally active with high safety profile:

1. MTD in Rat : >100 mg/kg/day;

2. No System toxicity in Rat & Dog: 100 mg/kg/day

3. LD50>1,000mg/kg/day in Dogs

4. NOEL (No Observed Effect Level) Teratology : >80 mg/kg

5. NOAEL (No Observed Adverse Effect Level) in Rat & Dog = 30 mg/kg/day

Wide spectrum anti solid tumor effects

BROAD SPECTRUM ANTI CANCER PROPERTIES:

Antroquinonol inhibited the growth of various types

of cancer cells in culture

NS398

(COX-2

inhibitor)

AC

(110mg/kg)

AC

(55mg/kg)Control

Source:

Antrodia camphorata inhibits

proliferation of human breast

cancer cells in vitro and in vivo.

Food and Chemical Toxicology

46 (2008) 2680–2688

Effective In vivo inhibition of MDA-MB-231 Breast cancer tumor

Comparison against COX-2 inhibitor

Anti Breast Cancer Properties

Antroquinonol inhibits NSCLC proliferation by altering PI3K/mTOR proteins and miRNA expression profiles; Mutation Research 707 (2011) 42–52

Lung Cancer cells: Anti proliferative effect

Liver Cancer cells: Anti proliferative effect

Antroquinonol displays anticancer

potential against human

hepatocellular carcinoma cells: A

crucial role of AMPK and mTOR

pathways; Biochem Pharmacol.

2010 Jan 15;79(2):162-71.

PMID:19723512

Source:

The Augmented Anti-Tumor

Effects of Antrodia

camphorata Co-Fermented

with Chinese Medicinal Herb

in Human Hepatoma Cells;

The American Journal of

Chinese Medicine, Vol. 37,

No. 4, 771–783;

Adjuvant with cisplatin & paclitaxel

26

Anti Liver Cancer Properties

HepG2 Liver Cancer cells

Source: The adjuvant effects of Antrodia Camphorata extracts combined with anti-tumor agents on multidrug resistant human hepatoma cells. Journal of Ethnopharmacology118 (2008) 387–395

Anti Liver Cancer Properties

Adjuvant with Chemotherapy

Multidrug resistant (A)C3A & (B)PLC/PRF/5

hepatoma cells

• Under go targeted chemo therapy

• Nesavar (Sorafenib) 30 days

Clinical Case Report

Patient (Diabetic with Kidney Dialysis): • Suffered from primary Liver cancer.• 4 months after Liver resection, • Diagnose with late stage metastatic Lung cancer.

Diagnose with late stage metastatic Lung cancer.

CT scan show continue presence of Tumor

• Change chemo regime

• Take Antroquinonol 400mg / day x 24 days

CT scan show complete absence of Tumors

Antroquinonol®isolated from AC

Functions of Antroquinonol in adjuvant and combination chemotherapy:

• Increased cancer cell kill :

• Administration of drugs with different mechanisms of action.

• Suppression of drug resistance

• Helps reduced injury to normal cells :

• It provide Hepatoprotection against drug toxic side effects

• Support Immunity against infections

Clinical application:

Antroquinonol is currently use as adjuvant/combination agent to existing

chemotherapy or as primary agent for non options cancer patients.

December 2013:

Antroquinonol is approved by US FDA enter into phase 2 clinical trial (NCT01134016)

Common Symptoms of

Cancer Palliative Care Outpatients

• Pain 82%

• Easy fatigue 67%

• Weakness 64%

• Anorexia 64%

• Weight loss 60%

• Lack of energy 59%

• Dry mouth 55%

• Constipation 51%

• Dyspnea 51%

• Easy satiety 50%

• Sleep problems 47%

• Depression 40%

Adapted from Donnelly et al.

Cancer Type Range

Early disease 48% (38%-100%)

Advanced disease 74% (53%-100%)

Pancreas 72%-85%

Esophagus 71%-77%

Head & neck 67%-91%

Genitourinary 58%-90%

Prostate 56%-94%

Breast 40%-89%

Prevalence of Cancer Pain

Cancer Pain: Assessment and

Management. 2003:38-50:

Common Cancer Pain by Pathophysiology

• Bone metastases

• Skin lesions

• Malignant bowel obstruction

• Chemotherapy-induced peripheral neuropathy

Causes of Cancer Pain (Etiology) Prevalence

Due to cancer 85%-93%

Due to diagnosis & treatment 17%-21%

Unrelated to diagnosis & treatment 2%-9%

Pain;1995:63;65-76

Pain;1999:82:263-274

Causes of Cancer Pain

Isolated from Antrodia Camphorata

Isolated from Antrodia Camphorata

Effective chemopreventive agents:

Multi-pronged anti cancer approach

Wide spectrum cancer (type) targets

Cancer Chemoprevention

Anti-cancer

Anti cell promotion

Anti cell proliferation

Activate cell death

Anti-toxin

Detoxification,

strengthen liver functions

Anti-infection

Strengthen immune systems

Anti-oxidation

Major categories of chemopreventive agents

Treatment stages

Pre-Cancertherapy

During Chemotherapy

Post Chemotherapy

Application Mode:

Neo-Adjuvant / Complimentary

Adjuvant Preventive

Therapeutic Actions:

Anti oxidationAnti infection

Anti inflammation

HepatoprotectionImmune modulation

Tumor regression

ChemopreventionImmune

modulationAnti oxidation

AC in Cancer Applications Summary

Anti Initiation

Anti oxidation

Anti inflammation

Anti Promotion

• Growth inhibition

Anti Progression

• Induce apoptosis

AC simultaneously

attack the various

stages of cancer

formation

Antrodia CamphorataPowerful Natural Chemopreventive Compound

Centre for Adjuvant & Complementary Medicine

Company focus on offering Breakthrough Bio-Medical Product Solutions in major areas of Aging Health Concerns that helps in the Prevention of Chronic Illnesses of Modern Society, Extending and Enhancing the Quality of Life.

Company sub specialized in providing Pharmacological Therapy product solutions for: Chronic disease management Critical illness recovery Complimentary chemotherapy High risk chemoprevention

INTERNATIONAL ADVANCED BIO-PHARMACEUTICAL INDUSTRIES PTE LTD

8 Boon Lay Way, #08-03 TradeHub 21, Singapore 609964

Tel: +65-68738693 Fax: +65-68738694 URL: www.iabpi.com

李咨潮硕士 Mr LEE Chee Cheow (M.Sc. TCM Dip.)

科学主任首席咨询顾问

Chief Scientific Officer

Principal Consultant, IABPI

Author:

Chief Scientist, CAM Pharmacologist & Nutriceutical Consultant

Areas of research interest includes:

Naturopathic & Integrated Medicine

Chemopreventive Therapy

Transdermal Drug Delivery system.