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.