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Galectin-3 and the Role ofModified Citrus Pectinand Botanicals inIntegrative Oncology
What is Galectin-3?•   Member of soluble β galactoside-binding    lectins•   Plays important regulatory roles in    cancer...
Galectin-3 Plays Regulatory      Role in InflammationBiologically active marker for high risk       Unlike CRP which repre...
Galectin-3 Levels & Mortality from All Causes         in the General Population: PREVEND1                                 ...
Galectin-3 & Cancer•   In Cancer, Galectin-3 plays a role in:    •   Cell to Cell Adhesion    •   Aggregation of Cancer Ce...
Blood Vessel
Blood Vessel
Modified Citrus Pectinand Galectin-3
What is Modified Citrus Pectin (MCP?)•   MCP is derived from the pith of citrus fruit peels –    oranges, lemons, grapefru...
Modified Citrus Pectin is a Galectin-3      Blocker•   Binds to Galectin-3 molecules•   Blocks aggregation of cancer cells...
Modified Citrus Pectin andGalectin-3
Modified Citrus PectinCancer Research
Benefits of MCP in Cancer Treatment•   Anti-Cancer and Anti-Metastasis•   Blocking of Galectin-3 Effects•   Synergistic Ef...
Inhibition of Spontaneous Metastasis in a Rat        Prostate Model by Oral Administration of        Modified Citrus Pecti...
Inhibition of Human Cancer Cell Growth & Metastasis          in Nude Mice by Oral Intake of Modified Citrus Pectin3       ...
Modified Citrus Pectin Induces Cytotoxicity of Prostate                         Cancer Cells in Co-Culture with Human Endo...
Effect of Modified Citrus Pectin on PSA Doubling Time                            in Prostate Cancer Patients: A Pilot Clin...
Pilot Clinical Results: MCP’s Effect on      PSA Doubling Time5            MCP Use    PSADT Patient    (Months)   Change  ...
Modified Citrus Pectin Increases the Prostate-Specific      Antigen Doubling Time in Men with Prostate Cancer: A      Phas...
PSADT as % of Pre MCP                  50%                        100%                               150%                 ...
Using Splines to Detect Changes inPSA Doubling Times7Guess B, Jennrich R, Johnson H, Redheffer R, Scholz M, Healing Touch ...
Typical Patient Results7       MCP
Clinical Benefit in Patients with         Advanced Solid Tumors Treated with         Modified Citrus Pectin8         Azéma...
Inhibitory Effect of Modified Citrus Pectin         on Liver Metastasis in a Mouse         Colon Cancer Model9         Liu...
PectaSol-C Modified Citrus Pectin Induces Apoptosis &          Inhibition of Proliferation in Human & Mouse Androgen      ...
Combination Effect of PectaSol and Doxorubicin on          Viability, Cell Cycle Arrest and Apoptosis in DU-145 and       ...
MCP During Chemotherapy &    Radiation• MCP can enhance therapeutic effect of  chemotherapy drugs and treatment of chemo  ...
Summary: MCP in Cancer Treatment   MCP Reduces:   • Primary Tumor   • Angiogenesis   • Metastatic Process   MCP Provides: ...
Modified Citrus PectinImmune Research
Activation of Human T-Cytotoxic Cell, B-Cell, and       Natural Killer (NK)-Cells and Induction of NK-Cell Activity       ...
Results Part I:                                                    MCP Activates T-Cytotoxicity13                         ...
Results Part I:                                          MCP Increases B-Cell Activation13                                ...
Results Part I:                                       MCP Increases NK Cell Activation13                                  ...
MCP: Induction of NK-Cell Activity Against    K562 Chronic Myeloid Leukemia Cells13• Method (Part II):  NK cell ability to...
Results Part II:                                                                          MCP Induces NK Cell Activity13  ...
MCP Immune System Benefits• Induces NK Cell Activation• Induces NK Cell Activity• Activates T Cell Cytotoxicity• Increases...
Modified Citrus Pectin:Chelation &Detoxification Research
MCP Heavy Metal       Elimination14• Forms stacked “egg  box” structure• Each pocket negatively  charged• Negative charge ...
The Effect of Modified Citrus Pectin on       Urinary Excretion of Toxic Elements14       Eliaz I, Hotchkiss AT, Fishman M...
The Effect of Modified Citrus Pectin on                                Urinary Excretion of Toxic Elements14              ...
MCP & Urinary Excretion of Toxins14MCP Chelation:• Increased urinary excretion of toxic metals• Demonstrated heavy metal c...
Modified Citrus Pectin Decreases      Total Mercury Body Burden:      Pilot Human Clinical Trial15      Eliaz I, Amitabha ...
Mercury Body Burden Results15                       ug Mercury /g Creatinine                                              ...
Mercury Body Burden Study15• Results: MCP  decreased total             % Mercury Reduction from Baseline  body burden in a...
The Role of Modified CitrusPectin as an EffectiveChelator of Lead inChildren Hospitalized withToxic Lead Levels16Zhao ZY, ...
Lead in Blood Serum16                                         60                                                          ...
Lead in 24 Hour Urine Excretion16                       140                                                               ...
Summary: Benefits of     Modified Citrus Pectin•   Galectin-3 Blocker•   Anti-Cancer•   Immunity•   Chelation and Detox
Research: Synergistic Benefits of MCPw/Botanical Formulas
Prostate Poly Botanical Formula Integrative blend of    33 ingredients:  Vitamins, Minerals,Botanically EnhancedMedicinal ...
ProstaCaid
ProstaCaid Induces G2/M Cell Cycle Arrest & Apoptosis             in Human & Mouse Androgen-Dependent & -             Inde...
Suppression of Growth and Invasive Behaviorof Human Prostate Cancer Cells by ProstaCaid:Mechanism of Activity18Jiang, J, E...
Effect of ProstaCaid on Invasive Behavior                                   of Prostate Cancer Cells18                    ...
Study Highlights18•
ProstaCaid Inhibits Tumor Growth in a        Xenograft Model of Human Prostate Cancer19        Jiang J, Loganathan J, Elia...
ProstaCaid Inhibits Tumor Growth in a       Xenograft Model of Human Prostate Cancer19Results:No effect on body weight or ...
Breast Poly Botanical FormulaContainsbotanicals, purifiedbiologically activenutritional compounds andbotanically enhancedm...
BreastDefend
Suppression of Proliferation & InvasiveBehavior of Human Metastatic Breast CancerCells by Dietary Supplement BreastDefend2...
BreastDefend Suppresses MDA-MB-231         Growth and Breast-to-Lung Metastasis in         Tumor Model (Pre-Published Data...
Synergistic and Additive Effects ofModified Citrus Pectin with Two NovelPoly Botanical Compounds, in theSuppression of Inv...
Proliferation Index (%) .   ProstaCaid21
ProstaCaid & MCP21              120              100               80                  P<0.01% Migration                  ...
BreastDefend21                          120Proliferation Index (%)                          100                           ...
BreastDefend & MCP21              120              100                                 P<0.01              80% Migration  ...
Honokiol•   Honokiol is a small-molecule polyphenol isolated from    the genus Magnolia officinalis (Hou Po)•   Properties...
HonokiolMechanisms of Action• Modulation of GABA receptors• Blocks signaling in tumors with defective p53 function  and ac...
Selected Honokiol Cancer Research22,23,24•   Honokiol traverses the blood-brain barrier and induces    apoptosis of neurob...
Selected Honokiol Cancer Research25,26,27•   Honokiol produces anti-neoplastic effects on melanoma cells    in vitro. Mann...
Selected Honokiol Cancer Research28,29,30•   Apoptosis induced by Magnolia Grandiflora extract in    chlorambucil-resistant...
Effect of HonoPure (98% Honokiol) onGrowth of PC3 Cells (Pre-Published data)                           120                ...
Effect of HonoPure (98% Honokiol) onthe Growth of MDA-MB-231 Cells(Pre-Published Data)                            120     ...
Synergistic Effect of PectaSol-C MCP &HonoPure (98% Honokiol) on PC3 Cell lineMigration (Pre-Published Data)
Honokiol Clinical Use and Dosages•   Active Cancer    1,000 mg x 3/day, with food•   Prevention and Post-Therapy    1000 m...
Galectin-3Breakthrough Research
Galectin-3 Levels & Mortality from All Causes                                   in the General Population: PREVEND1       ...
Galectin-3 in General Population:                 PREVEND (number of subjects = 7,968)                     1CHARACTERISTIC...
Galectin-3 in General Population:                 PREVEND (number of subjects = 7,968)                         1CHARACTERI...
COACH Galectin-3 Sub-Study                               Mortality from All Causes at 1 Year                              ...
Research: Elevated Galectin-3 Implicated in a         Wide Variety of Disease States• Cardiovascular Diseases32  Elevated ...
Modified Citrus PectinReduces Galectin-3Expression and DiseaseSeverity in ExperimentalAcute Kidney Injury37
MCP & Kidney Injury Study37Background: Folic acid (FA)-induced acute kidney injury model.Method: Mice given 1% MCP-supplem...
Serum Galectin-3TestingFDA approved blood test measures        Circulating Galectin-3 for          Cardiovascular Disease
Elevated Galectin-3:      What can we do?•   Test for Galectin-3 levels•   Address general inflammation & hyper    viscosi...
Galectin-3 Levels: Reference Ranges•   Galectin-3 levels > 17.8 ng/ml are considered to be an    extreme risk factor of mo...
Galectin-3 Levels: MCP DosageActive Cancer•   Levels <17.8    MCP 15g daily•   Levels >17.8    MCP 20 - 25g daily
Galectin-3 Levels: MCP Dosage••••
In Conclusion•   Galectin-3 plays an important role in    prevention, treatment and prognosis    of multiple medical condi...
Thank you!www.facebook.com/dreliaz   ieliaz@sonic. net    www.dreliaz.org
Isaac Eliaz OncANP Feb 2012
Isaac Eliaz OncANP Feb 2012
Isaac Eliaz OncANP Feb 2012
Isaac Eliaz OncANP Feb 2012
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Isaac Eliaz OncANP Feb 2012

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Isaac Eliaz OncANP Feb 2012

  1. 1. Galectin-3 and the Role ofModified Citrus Pectinand Botanicals inIntegrative Oncology
  2. 2. What is Galectin-3?• Member of soluble β galactoside-binding lectins• Plays important regulatory roles in cancer, inflammation, fibrosis, and immunologic response• Expressed in the nucleus, cytoplasm, mitochondria, cell surface, and circulation
  3. 3. Galectin-3 Plays Regulatory Role in InflammationBiologically active marker for high risk Unlike CRP which represents the result or “bystander” biomarker, Galectin-3 is a “culprit” biomarker• Promotes metastasis, inflammation & fibrosis• Predicts outcome
  4. 4. Galectin-3 Levels & Mortality from All Causes in the General Population: PREVEND1 Median Galectin-3 Levels Overall AverageNumber of Subjects n = 7,968 11.9
  5. 5. Galectin-3 & Cancer• In Cancer, Galectin-3 plays a role in: • Cell to Cell Adhesion • Aggregation of Cancer Cells • Tumor Growth • Metastasis • Angiogenesis • Inhibition of Apoptosis
  6. 6. Blood Vessel
  7. 7. Blood Vessel
  8. 8. Modified Citrus Pectinand Galectin-3
  9. 9. What is Modified Citrus Pectin (MCP?)• MCP is derived from the pith of citrus fruit peels – oranges, lemons, grapefruit• Complex polysaccharide fiber of repeating galacturonic acid groups with neutral sugar side chains• Unmodified citrus pectin molecular weight 50 to 300 kiloDaltons (kDa) with esterification ~70%• Optimal biological activity: molecular weight <13 kDa with esterification <10%, and specific structure
  10. 10. Modified Citrus Pectin is a Galectin-3 Blocker• Binds to Galectin-3 molecules• Blocks aggregation of cancer cells• Blocks docking of cancer cells• Blocks interactions with endothelium necessary for angiogenesis
  11. 11. Modified Citrus Pectin andGalectin-3
  12. 12. Modified Citrus PectinCancer Research
  13. 13. Benefits of MCP in Cancer Treatment• Anti-Cancer and Anti-Metastasis• Blocking of Galectin-3 Effects• Synergistic Effect with Chemotherapy• Protection Against Post-Radiation Damage• Improved Quality of Life
  14. 14. Inhibition of Spontaneous Metastasis in a Rat Prostate Model by Oral Administration of Modified Citrus Pectin2 Pienta KJ, Naik H, Akhtar A, Yamazaki K, Replogle, TS, Lehr J, Donat TL, Tait L, Hogan V, Raz A Wayne State University School of Medicine, Detroit, MI, USA J Natl Cancer Inst. 1995 87(5):348-53• Method: MCP’s inhibition of prostate cell adhesion to endothelial cells. 0.1% and 1.0% MCP in rats’ drinking water; controls had plain water.• Results: Significant reduction in lung metastases -- 50% reduction in 0.1% group; 56% reduction in 1.0% group (P<0.03 & P<0.001).• Conclusion: MCP acted as potent inhibitor of spontaneous prostate carcinoma metastasis.
  15. 15. Inhibition of Human Cancer Cell Growth & Metastasis in Nude Mice by Oral Intake of Modified Citrus Pectin3 Nangia-Makker P, Hogan V, Honjo Y, Baccarini S, Tait L, Bresalier R, Raz A Wayne State University, School of Medicine, Detroit, MI, USA J Natl Cancer Inst. 2002 94(24): 1854-62• Method: MCP’s inhibition of breast & colon cancer progression; MCP’s interaction with Galectin-3.• Results: 70.2% Reduction in Breast Tumor Growth – Breast Angiogenesis: 66% Reduction – Breast to Lung Metastasis: 0% MCP v. 100% Control – Colon to Liver Metastasis: 0% MCP v. 60% Control – Colon to Lymph Metastasis: 25% MCP v. 100% Control• Conclusion: MCP inhibits carbohydrate mediated tumor growth, angiogenesis & metastasis via effects on Galectin-3 function.
  16. 16. Modified Citrus Pectin Induces Cytotoxicity of Prostate Cancer Cells in Co-Culture with Human Endothelial Monolayers4 Weiss T, McCulloch M, Eliaz I Amitabha Medical Clinic & Healing Center, Sebastopol, CA, USA EcoNugenics, Santa Rosa, CA,USA Intl Conference on Diet & The Prevention of Cancer 1999, Tampere, Finland 90% 76.9% 80.7% • Method: Human 80% vascular endothelial cell% Cytotoxicity 70% 60% layer & PC-3 prostate 50% cancer cells. 40% 30% • Results: Strong tumor 20% 10% 3.8% cell death response 0% with MCP, compared to Control 0.1% 1.0% controls.
  17. 17. Effect of Modified Citrus Pectin on PSA Doubling Time in Prostate Cancer Patients: A Pilot Clinical Trial5 Strum S, Scholz M, McDermed J, McCulloch M, Eliaz, I Prostate Oncology Specialist, Marina del Rey, CA, USA Amitabha Medical Clinic & Healing Center, Sebastopol, CA, USA EcoNugenics, Santa Rosa, CA, USA. International Conference on Diet & The Prevention of Cancer 1999, Tampere, Finland • Method: MCP 15 g/day 80% 71% to patients with 70% biochemical relapse% Increase in PSADT 60% 50% post local therapy. PSA 40% Doubling Time (PSADT) 30% evaluated at intervals. 14% 14% 20% • Results: MCP 10% significantly increased 0% PSADT in prostate No Response Stable Disease Response cancer patients.
  18. 18. Pilot Clinical Results: MCP’s Effect on PSA Doubling Time5 MCP Use PSADT Patient (Months) Change StatusPatient 1 5 193% ResponsePatient 2 6 193% ResponsePatient 3 3 80% ResponsePatient 4 >15 55% ResponsePatient 5 6 6% P. ResponsePatient 6 6 -7% Stable DiseasePatient 7 5 -69% No Response
  19. 19. Modified Citrus Pectin Increases the Prostate-Specific Antigen Doubling Time in Men with Prostate Cancer: A Phase II Pilot Study6 Guess BW, Scholz MC, Strum SB, Lam RY, Johnson HJ, Jennrich RI Healing Touch Oncology, Marina del Rey, CA, USA Prostate Cancer & Prostatic Disease 2003;6(4):301-4• Method: 10 men with biochemical prostate cancer relapse used MCP: 15g daily for 1 year.• Results: MCP significantly increased PSADT in 7 out of the 10 participants (p<0.01).
  20. 20. PSADT as % of Pre MCP 50% 100% 150% 200% 250% 300% 350% 400% 450% 500% 0% * Patient-1 * Patient-2 Patient-3 Patient-4 Phase II Study: Post-MCP Patient-5 Patient-6 Pre-MCP Patient-7 PSADT Results After 1 Year6 Patient-8 Patient-9Patient-10 968 %
  21. 21. Using Splines to Detect Changes inPSA Doubling Times7Guess B, Jennrich R, Johnson H, Redheffer R, Scholz M, Healing Touch Oncology, Marin delRay, CA, Department of Statistics, University of California Los Angeles, CA, Department ofMathematics, University of California - Los Angeles, CA, The Prostate 2003 54:88-95
  22. 22. Typical Patient Results7 MCP
  23. 23. Clinical Benefit in Patients with Advanced Solid Tumors Treated with Modified Citrus Pectin8 Azémar M, Hildenbrand B, Haering B, Heim ME, Unger C Albert-Ludwigs-University in Freiburg, Germany Sonnenberg-Klinik, Bad Sooden-Allendorf, Germany Clinical Medicine: Oncology 2007 1:73–80• Method: MCP 15g daily.• Results: 49 patients with advanced solid tumors. 29 evaluated after 2 months -- 21% showed stabilization & improvements in quality of life. – One patient w/ metastasized prostate carcinoma showed 50% decrease in PSA, with significant increase in quality of life & decrease in pain.• Conclusion: MCP shows clinical benefits & improvements in quality of life in advanced cancer patients.
  24. 24. Inhibitory Effect of Modified Citrus Pectin on Liver Metastasis in a Mouse Colon Cancer Model9 Liu HY, Huang ZL, Yang GH, Lu WQ, Yu NR Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou, China World J Gastroenterol 2008 14(48): 7386-7391• Method: 5 groups of 15 mice. MCP: 0.0%, 1.0%, 2.5% and 5.0%; and negative control – Colon cancer cells injected into spleen except negative control -- liver metastasis observed after 3 wks. ELISA used to detect Galectin-3.• Results: MCP groups: metastasis 80%, 73.3% & 60%. MCP 0.0%: metastasis100%.• Conclusion: MCP significantly reduced liver metastasis.
  25. 25. PectaSol-C Modified Citrus Pectin Induces Apoptosis & Inhibition of Proliferation in Human & Mouse Androgen Dependent & Independent Prostate Cancer Cells10 Yan J, Katz A Department of Urology, Columbia University Medical Center, New York, NY, USA Integrative Cancer Therapies 2010 9:197-203• Method: 1% MCP treatment of human prostate cancer cell lines (LNCaP & PC3) and mouse prostate cancer cell lines (CASP2-1 & CASP1-1)• Results: Confirmed apoptosis and inhibition of cancer cell proliferation. 4 day MCP treatment showed cytotoxicity: – 52.28% in LNCaP – 48.16% in PC3 – 23.03% in CASP2-1 – 49.01% in CASP1-1
  26. 26. Combination Effect of PectaSol and Doxorubicin on Viability, Cell Cycle Arrest and Apoptosis in DU-145 and LNCaP Prostate Cancer Cell Lines11 Najmeh T, Houri S, Parvin M, Firouzeh B, Arash HN, Abdolfattah S, Ebrahim H Tehran University, Tehran, Iran Cell Biology International (2012) Immediate Publication, doi:10.1042/CBI20110309 • Method: 48 hour effects of PectaSol on Doxorubicin (Dox) cytotoxicity, apoptosis and cell cycle in prostate cancer cell lines. % Viability DU-145 % Viability LNCaP 100 IC50 Decrease: 1.5 fold 100 IC50 Decrease: 1.3 fold 80 80 60 60 40 40 20 20 0 0 Control 250nM 3mg/ml 250nM + Control 250nM 3mg/ml 250nM + 3 Dox PectaSol 3 mg/ml Dox PectaSol mg/ml Combined Combined• Conclusion: Lower, less toxic doses Dox needed when combined with PectaSol.
  27. 27. MCP During Chemotherapy & Radiation• MCP can enhance therapeutic effect of chemotherapy drugs and treatment of chemo resistant cancers. 11, 12 Cisplatin (Platinol), Bortezomib (Velcade), Dexamethasone (Decadron), Doxorubicin.• MCP use very important in preventing post chemotherapy & radiation damage Specifically post radiation induced inflammation and fibrosis
  28. 28. Summary: MCP in Cancer Treatment MCP Reduces: • Primary Tumor • Angiogenesis • Metastatic Process MCP Provides: • Blocking of Galectin-3 Effects • Synergistic Effect with Chemotherapy • Protection Against Post-radiation Damage • Improved Quality of Life
  29. 29. Modified Citrus PectinImmune Research
  30. 30. Activation of Human T-Cytotoxic Cell, B-Cell, and Natural Killer (NK)-Cells and Induction of NK-Cell Activity Against K562 Chronic Myeloid Leukemia Cells with Modified Citrus Pectin 13 Ramachandran C, Wilk, B, Hotchkiss, A, Eliaz, I & Melnick SJ; Dharma Biomedical, Miami, FL, USA; EcoNugenics, Santa Rosa, CA, USA ; Eastern Regional Research Center, ARS, USDA, Wyndmoor, PA, USA; Department of Pathology, Miami Childrens Hospital, Miami, FL 33155, USA BMC Complementary and Alternative Medicine 2011, 11:59• Method (Part I): Healthy human blood samples incubated with increasing doses of MCP and antibodies. At 24 hours samples lyzed and run on a flow cytometer. Analyzed % of activated T-cytotoxic cell subset, B- cells, and NK-cells; and % increase over untreated control.
  31. 31. Results Part I: MCP Activates T-Cytotoxicity13 160% * p < 0.05 **Increase in T-Cytotoxic Cell Activation(%) 140% ** p < 0.01 120% * * 100% 80% 60% 40% 20% 0% MCP MCP MCP MCP MCP CD2/CD2R PMA 50 100 200 400 800 20 10 ug/ml ug/ml ug/ml ug/ml ug/ml ul/ml ng/ml
  32. 32. Results Part I: MCP Increases B-Cell Activation13 1200% *** 1000% ** p<0.010 **Increased B-Cell Activation (%) *** p<0.001 800% 600% 400% 200% 0% MCP MCP MCP MCP MCP MCP MCP PWM PWM 10 20 50 100 200 400 800 10 25 ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml
  33. 33. Results Part I: MCP Increases NK Cell Activation13 1000% ** 900%Increased NK-Cell Activation (%) 800% 700% ** 600% 500% 400% * * 300% 200% 100% 0% MCP MCP MCP MCP MCP MCP MCP IL-2 IL-2 10 20 50 100 200 400 800 3.3 6.6 ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml ng/ml ng/ml
  34. 34. MCP: Induction of NK-Cell Activity Against K562 Chronic Myeloid Leukemia Cells13• Method (Part II): NK cell ability to induce leukemia cell death analyzed by co-incubating MCP-treated lymphocytes with K562 T-cell leukemia cells. Healthy human lymphocyte samples treated with increasing doses of MCP. After 24 hours, K562 labeled. Plates returned to incubator (for 4 hrs) to induce leukemia cell death.
  35. 35. Results Part II: MCP Induces NK Cell Activity13 60% (% K562 cell death over untreated WBC) 50%Increase in NK Cell Activity 40% 30% 20% 10% 0% MCP MCP MCP MCP MCP MCP MCP 10 20 50 100 200 400 800 ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml ug/ml
  36. 36. MCP Immune System Benefits• Induces NK Cell Activation• Induces NK Cell Activity• Activates T Cell Cytotoxicity• Increases B Cell Activation
  37. 37. Modified Citrus Pectin:Chelation &Detoxification Research
  38. 38. MCP Heavy Metal Elimination14• Forms stacked “egg box” structure• Each pocket negatively charged• Negative charge binds heavy metals• Toxic metal trapped in the “egg box”• Safely excreted from the body
  39. 39. The Effect of Modified Citrus Pectin on Urinary Excretion of Toxic Elements14 Eliaz I, Hotchkiss AT, Fishman ML, Rode D; Amitabha Medical Clinic & Healing Center, Sebastopol, CA, USA; Eastern Regional Research Center, ARS, USDA, Wyndmoor, PA, USA; University of California, Davis, CA, USA ; Phytother Res. 2006 20(10):859-64• Methods: MCP administered for 6 days. Baseline 24 hr urine collection before MCP, and on days 1 and 6. Days 1 - 5: MCP 15 g/day & Day 6: MCP 20 g/day.• Results: Urinary excretion of lead, mercury, cadmium & arsenic increased. Essential minerals not changed. No side effects reported.
  40. 40. The Effect of Modified Citrus Pectin on Urinary Excretion of Toxic Elements14 Day-1 Day-6 450% # 400% * p < .05 # p < .10 350%% Change from Day Zero 300% 250% 200% 150% # 100% 50% * # * * # 0% Al… Sb… As… CD… Pb… Hg… Sn…
  41. 41. MCP & Urinary Excretion of Toxins14MCP Chelation:• Increased urinary excretion of toxic metals• Demonstrated heavy metal chelation due to reduced molecular size & esterification• 10% rhamnogalacturonan II -- known for binding affinity and immune enhancement• Does not affect essential minerals• No side effects reported
  42. 42. Modified Citrus Pectin Decreases Total Mercury Body Burden: Pilot Human Clinical Trial15 Eliaz I, Amitabha Medical Clinic & Healing Center, Sebastopol, California, USA EcoNugenics, Santa Rosa, California, USA 228th ACS National Meeting, Philadelphia PA. 2004• Method: 5g MCP 3x/day; 4-10 months. Baseline and final total mercury body burden measured using IV DMPS challenge.• Results: All subjects showed significant decrease in mercury levels. Avg decrease: 62.17% (p=0.03). No side effects reported.
  43. 43. Mercury Body Burden Results15 ug Mercury /g Creatinine Percent Duration of Patient Post Change in Baseline Difference Intervention Number Intervention Mercury (months) BurdenPatient 1 14 4.5 9.5 67.86% 10.0Patient 2 180 49.0 131 72.78% 4.5Patient 3 16 9.9 6.1 38.13% 4.0Patient 4 29 7.3 21.7 74.83% 6.5Patient 5 22 9.4 12.6 57.27% 6.5
  44. 44. Mercury Body Burden Study15• Results: MCP decreased total % Mercury Reduction from Baseline body burden in all subjects 80% 70% 67.90% 72.80% 74.80% – Average decrease 60% 57.30% 62.17% 62.17% (p=0.03) 50% 38.10% 40%• MCP is a promising 30% 20% systemic chelator 10% of heavy metals 0% that can be used on Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Avg an ongoing basis 10 mo 4.5 mo 4 mo 6 mo 6.5 mo
  45. 45. The Role of Modified CitrusPectin as an EffectiveChelator of Lead inChildren Hospitalized withToxic Lead Levels16Zhao ZY, Liang L, Fan X, Yu Z, Hotchkiss AT, Wilk BJ, Eliaz IChildren’s Hospital, Zhejiang University, School ofMedicine, Hangzhou, Republic of China, CentraxInternational, Inc, San Francisco, California, USAEastern Regional ResearchCenter, ARS, USDA, Wyndmoor, Pennsylvania, USAEcoNugenics, Santa Rosa, California, USAAltern Ther Health Med. 2008 14(4):34-8
  46. 46. Lead in Blood Serum16 60 Before AfterBlood Serum Lead Concentration (ug/dL) MCP MCP 50 40 30 20 10 0 Patient-1 Patient-2 Patient-3 Patient-4 Patient-5 Patient-6 Patient-7 (MCP 5 grams, 3 times daily) P Value = 0.0016
  47. 47. Lead in 24 Hour Urine Excretion16 140 Before After MCP MCP 120 100Lead Levels (mcg/dL) 80 60 40 20 0 Patient-1 Patient-2 Patient-3 Patient-4 Patient-5 Patient-6 Patient-7 (MCP 5 grams, 3 times daily) P Value = 0.0007
  48. 48. Summary: Benefits of Modified Citrus Pectin• Galectin-3 Blocker• Anti-Cancer• Immunity• Chelation and Detox
  49. 49. Research: Synergistic Benefits of MCPw/Botanical Formulas
  50. 50. Prostate Poly Botanical Formula Integrative blend of 33 ingredients: Vitamins, Minerals,Botanically EnhancedMedicinal Mushrooms,and Botanical Extracts
  51. 51. ProstaCaid
  52. 52. ProstaCaid Induces G2/M Cell Cycle Arrest & Apoptosis in Human & Mouse Androgen-Dependent & - Independent Prostate Cancer Cells 17 Yan J & Katz AE; Department of Urology, Columbia University Medical Center, New York, NY, USA. Integr Cancer Ther 2010 9:186-196Effects on cell viability on androgen- Effects on long-term cell viability by colonydependent, LNCaP (A) & CASP 2.1 (C), & androgen- formationindependent PC3 (B) & CASP 1.1 (D)
  53. 53. Suppression of Growth and Invasive Behaviorof Human Prostate Cancer Cells by ProstaCaid:Mechanism of Activity18Jiang, J, Eliaz, I, and Sliva, D; Cancer Research Laboratory, Methodist ResearchInstitute, Indianapolis, IN,USA ; Amitabha Medical Clinic & HealingCenter, Sebastopol, CA, USAIndiana Univer. Cancer Center, Indiana Univer. School of Med., Indianapolis, IN, USAInt J Oncol. 2011 Jun;38(6):1675-82 120 0 g/ml 10 g/ml 20 g/ml 100 Proliferation Index (%) 40 g/ml * 80 g/ml * 80 * * * * 60 * * 40 * * 20 * 0 24 hours 48 hours 72 hours
  54. 54. Effect of ProstaCaid on Invasive Behavior of Prostate Cancer Cells18 120 120 Cell migration [%]Cell adhesion [%] 100 100 80 * 80 * 60 60 * * 40 40 20 20 0 0 0 20 40 80 0 20 40 80 ProstaCaid (g/ml) ProstaCaid [g/ml] 120Cell invasion [%] 100 * 80 * 60 40 20 0  0 20 40 80 ProstaCaid [g/ml]
  55. 55. Study Highlights18•
  56. 56. ProstaCaid Inhibits Tumor Growth in a Xenograft Model of Human Prostate Cancer19 Jiang J, Loganathan J, Eliaz I, Terry C, Sandusky GE, Sliva D; Cancer Research Laboratory, MRI, Indiana University Health, Indianapolis, IN, USA; Amitabha Medical Clinic and Healing Center, Sebastopol, CA, USA; Indiana University. Simon Cancer Center, Indiana University. School of Med., Indianapolis, IN, USA, Intern J of Oncol 2012; Doi:10.3892/ijo.2012.1344• Method: ProstaCaid in xenograft model of human hormone refractory PC3 prostate cancer - (100, 200 and 400 mg/kg)
  57. 57. ProstaCaid Inhibits Tumor Growth in a Xenograft Model of Human Prostate Cancer19Results:No effect on body weight or activity of liver enzymes (ALT, AST)No sign of toxicity in liver, spleen, kidney, lung and heart tissuesin miceInhibition of tumor volumes (1024.6 378.6 vs.749.3 234.3, P<0.001)qRT-PCR analysis demonstrated significant up regulation ofexpression of CDKN1A (p21) and inhibition of expression ofIGF2, NR2F2 and PLAU (uPA)Conclusion: ProstaCaid has significant anticancer activity in vivowith no signs of toxicity.
  58. 58. Breast Poly Botanical FormulaContainsbotanicals, purifiedbiologically activenutritional compounds andbotanically enhancedmedicinal mushrooms
  59. 59. BreastDefend
  60. 60. Suppression of Proliferation & InvasiveBehavior of Human Metastatic Breast CancerCells by Dietary Supplement BreastDefend20Jiang J, Wojnowski R, Jedinak A, Sliva D; Cancer Research Laboratory, Methodist ResearchInstitute, Indianapolis, IN, USA Department of Medicine, Indiana University. CancerCenter, School of Med., Indiana University, Indianapolis, IN, USA; Integr Cancer Ther.2011; Jun 10 (2):192 – 200 0g/ml 120 10 g/ml 20 g/ml 30 g/ml 100 40 g/ml Proliferation Index [%] 80 * * 60 * * * 40 * 20 * * * * 0 24 hours 48 hours 72 hours
  61. 61. BreastDefend Suppresses MDA-MB-231 Growth and Breast-to-Lung Metastasis in Tumor Model (Pre-Published Data)• Method: Human breast cancer cells (MDA-MB-231) implanted into the mammary gland in mice Pre-Published Results: BreastDefend significantly decreased tumor volume and breast-to-lung metastasis in highly aggressive triple negative breast cancer, without toxicity.
  62. 62. Synergistic and Additive Effects ofModified Citrus Pectin with Two NovelPoly Botanical Compounds, in theSuppression of Invasive Behavior ofHuman Breast and Prostate CancerCells21Jiang J, Eliaz I, and Sliva DCancer Research Laboratory, MRI, Indiana UniversityHealth, Indianapolis, IN, USAAmitabha Medical Clinic & Healing Center, Sebastopol, CA, USADepart. of Med., and Indiana Univer. Cancer Center, IndianaUniver. School of Med., Indianapolis, IN, USA.Integr Cancer Ther. 2012 (In Press)
  63. 63. Proliferation Index (%) . ProstaCaid21
  64. 64. ProstaCaid & MCP21 120 100 80 P<0.01% Migration P<0.01 60 40 P<0.01 20 0MCP 0 0.25 0.5 1.0 0 0.25 0.5 1.0 mg/mlProstaCaid 10 10 10 10 g/ml
  65. 65. BreastDefend21 120Proliferation Index (%) 100 80 60 40 20 0 0 5 10 20 40
  66. 66. BreastDefend & MCP21 120 100 P<0.01 80% Migration P<0.01 60 P<0.01 40 20 0MCP 0 0.25 0.5 1.0 0 0.25 0.5 1.0 mg/mlBreastDefend 20 20 20 20 g/ml
  67. 67. Honokiol• Honokiol is a small-molecule polyphenol isolated from the genus Magnolia officinalis (Hou Po)• Properties • Anti-Tumor • Anti-Angiogenic • Anti-Inflammatory • Anti-Anxiety • Antioxidant • Selective Pro-Oxidant • Differentiation Agent • No Appreciable Toxicity • Synergistic Anticancer Effect w/ Multiple Chemotherapy Drugs
  68. 68. HonokiolMechanisms of Action• Modulation of GABA receptors• Blocks signaling in tumors with defective p53 function and activated ras by blocking activation of phospholipase D.• Induces cyclophilin D, potentiating mitochondrial permeability transition pore and causing death in cells with wild-type p53.• MTOR-1 Inhibitor
  69. 69. Selected Honokiol Cancer Research22,23,24• Honokiol traverses the blood-brain barrier and induces apoptosis of neuroblastoma cells via an intrinsic bax- mitochondrion-cytochrome c-caspase protease pathway. Lin JW, Chen JT, Hong CY, et al. Neuro Oncol. 2012 Jan 18.• Antimetastatic activity of honokiol in osteosarcoma. Steinmann P, Walters DK, E Arlt MJ, et al. Cancer. 2011 Sep 20. doi: 10.1002/cncr.26434.• Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells. Arora S, Bhardwaj A, Srivastava SK, et al. PLoS One. 2011;6(6):e21573.
  70. 70. Selected Honokiol Cancer Research25,26,27• Honokiol produces anti-neoplastic effects on melanoma cells in vitro. Mannal PW, Schneider J, Tangada A, et al. J Surg Oncol. 2011 Sep 1;104(3):260-4.• Honokiol radiosensitizes colorectal cancer cells: enhanced activity in cells with mismatch repair defects. He Z, Subramaniam D, Ramalingam S, Dhar A, et al. Am J Physiol Gastrointest Liver Physiol. 2011 Nov;301(5):G929-37.• Honokiol: a promising small molecular weight natural agent for the growth inhibition of oral squamous cell carcinoma cells. Chen XR, Lu R, Dan HX, et al. Int J Oral Sci. 2011 Jan;3(1):34-42.
  71. 71. Selected Honokiol Cancer Research28,29,30• Apoptosis induced by Magnolia Grandiflora extract in chlorambucil-resistant B-chronic lymphocytic leukemia cells. Marin GH, Mansilla E. J Cancer Res Ther. 2010 Oct-Dec;6(4):463-5.• Modulation of multidrug resistance p-glycoprotein activity by flavonoids and honokiol in human doxorubicin- resistant sarcoma cells (MES-SA/DX-5): implications for natural sedatives as chemosensitizing agents in cancer therapy. Angelini A, Di Ilio C, Castellani ML, et al. J Biol Regul Homeost Agents. 2010 Apr- Jun;24(2):197-205.• Honokiol induces paraptosis and apoptosis and exhibits schedule- dependent synergy in combination with imatinib in human leukemia cells. Wang Y, Yang Z, Zhao X. Toxicol Mech Methods. 2010 Jun;20(5):234-41.
  72. 72. Effect of HonoPure (98% Honokiol) onGrowth of PC3 Cells (Pre-Published data) 120 0  5  10  100 Proliferation Index (%) 20  * 40  * 80 * 60 * * 40 * 20 * * 0 24 hours 48 hours 72 hours
  73. 73. Effect of HonoPure (98% Honokiol) onthe Growth of MDA-MB-231 Cells(Pre-Published Data) 120 0  5  10  100 Proliferation Index (%) 20  * 40  80 * * 60 40 * * * 20 * 0 24 hours 48 hours 72 hours
  74. 74. Synergistic Effect of PectaSol-C MCP &HonoPure (98% Honokiol) on PC3 Cell lineMigration (Pre-Published Data)
  75. 75. Honokiol Clinical Use and Dosages• Active Cancer 1,000 mg x 3/day, with food• Prevention and Post-Therapy 1000 mg /day, with food• Anti-Inflammatory and Circulation Support 500 mg – 1,000 mg daily, with food• Anxiety and Insomnia 250 – 500 mg daily, with food
  76. 76. Galectin-3Breakthrough Research
  77. 77. Galectin-3 Levels & Mortality from All Causes in the General Population: PREVEND1 100% Median Galectin-3 Cumulative Survival Rate (%) Levels Quintile-1 95% 7.7 Quintile-2 9.4 90% Quintile-3 10.9 Quintile-4 12.6 85% Quintile-5 Start Year-5 Year-1 Year-2 Year-3 Year-4 Year-6 Year-7 Year-8 Year-9 Year-10 Year-11 15.6 Overall AverageNumber of Subjects n = 7,968 11.9
  78. 78. Galectin-3 in General Population: PREVEND (number of subjects = 7,968) 1CHARACTERISTIC TOTAL QUINTILE-1 QUINTILE-2 QUINTILE-3 QUINTILE-4 QUINTILE-5 P Median Gal3 11.9 7.7 9.4 10.9 12.6 15.6DM% 3.6 2.3 2.3 3.1 4.3 6.1 0.000MI 3.7 1.8 2.4 2.7 4.2 7.4 0.000Hypertension 33.4 22.2 26.6 31.1 39.7 47.9 0.000Stroke % 0.9 0.8 0.6 0.6 1.3 1.6 0.004Systolic BP 129.2 20.2 125.0 18.1 126.6 19.0 128.6 19.6 131.3 20.6 134.9 22.5 0.000Diastolic BP 74.0 9.7 72.1 9.4 73.3 9.8 74.1 9.6 75.2 9.8 75.4 9.8 0.000
  79. 79. Galectin-3 in General Population: PREVEND (number of subjects = 7,968) 1CHARACTERISTIC TOTAL QUINTILE-1 QUINTILE-2 QUINTILE-3 QUINTILE-4 QUINTILE-5 P Median Gal3 11.9 7.7 9.4 10.9 12.6 15.6 1.29 0.89 1.04 1.33 1.53 1.98CRP 0.000 [0.56-3.00] [0.39-2.16] [0.49-2.40] [0.58-2.92] [0.71-3.42] [0.85-4.28]Cholesterol 5.66 1.12 5.41 1.05 5.56 1.10 5.68 1.11 5.79 1.11 5.91 1.17 0.000LDL 3.69 1.05 3.47 1.00 3.60 1.01 3.71 1.04 3.77 1.05 3.90 1.06 0.000 1.27 1.32 1.28 1.25 1.24 1.24HDL 0.000 [1.03+1.56] [1.07-1.62] [1.04-1.57] [1.03+1.55] [1.03-1.53] [0.99-1.52] 1.16 1.02 1.11 1.17 1.23 1.31Triglycerides 0.000 [0.85-1.68] [0.75-1.43] [0.82-1.59] [0.86-1.69] [0.89-1.78] [0.95-1.92]
  80. 80. COACH Galectin-3 Sub-Study Mortality from All Causes at 1 Year in Patients with CHF31 40% 36.51% 35%% Died within 365 Days 30% 25% 19.69% 20% 15% 12.57% 10% 5% 0% < 17.8 17.8 - 25.9 > 25.9 Galectin-3 Levels (ng/mL)
  81. 81. Research: Elevated Galectin-3 Implicated in a Wide Variety of Disease States• Cardiovascular Diseases32 Elevated Galectin-3 linked with inflammation, heightened fibrosis, heart failure, coronary artery disease, peripheral artery disease, strokes, and vascular dementia.• Liver Disease33,34 Elevated Galectin-3 linked with extensive fibrosis of the liver. Reducing Galectin-3 resulted in improved hepatic health, including reduced inflammation, hepatocyte injury and fibrosis.• Gastrointestinal Conditions 35 Reducing Galectin-3 resulted in reduced inflammation in the gut mucosa -- important for treatment of ulcerative colitis, non-specific colitis, Crohn’s disease, Celiac disease and gluten sensitivity.• Type 2 Diabetes & Similar Metabolic Diseases36 Reducing Galectin-3 reduced inflammation in these conditions.
  82. 82. Modified Citrus PectinReduces Galectin-3Expression and DiseaseSeverity in ExperimentalAcute Kidney Injury37
  83. 83. MCP & Kidney Injury Study37Background: Folic acid (FA)-induced acute kidney injury model.Method: Mice given 1% MCP-supplemented water, or plain water, 1 week before FA injection.Results: During initial injury phase, all FA treated mice lost weight while their kidneys enlarged secondary to renal insult. • Gross changes significantly lessened in MCP group. • MCP clearly reduced renal cell proliferation. • Recovery phase: MCP group showed decreased Galectin-3 expression with decreased renal fibrosis, macrophages, pro-inflammatory cytokine expression, and apoptosis.
  84. 84. Serum Galectin-3TestingFDA approved blood test measures Circulating Galectin-3 for Cardiovascular Disease
  85. 85. Elevated Galectin-3: What can we do?• Test for Galectin-3 levels• Address general inflammation & hyper viscosity• Use MCP at appropriate dosages by: • Condition • Galectin-3 levels • Therapeutic goal
  86. 86. Galectin-3 Levels: Reference Ranges• Galectin-3 levels > 17.8 ng/ml are considered to be an extreme risk factor of mortality.• Ideal levels are < 14 ng/ml in the general population.• For cancer and cardiac patients, ideal levels are < 12 ng/ml.• Galectin-3 levels change in 20% of population every 3 months.• Repeated testing is important.
  87. 87. Galectin-3 Levels: MCP DosageActive Cancer• Levels <17.8 MCP 15g daily• Levels >17.8 MCP 20 - 25g daily
  88. 88. Galectin-3 Levels: MCP Dosage••••
  89. 89. In Conclusion• Galectin-3 plays an important role in prevention, treatment and prognosis of multiple medical conditions including cancer.• MCP is an effective natural Galectin-3 blocker.
  90. 90. Thank you!www.facebook.com/dreliaz ieliaz@sonic. net www.dreliaz.org

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