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A rational approach to helping cancer patients with natural therapies - Dr William Barnes MbChb Bsc (otago)\nFACNEM

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natural therapies and cancer

Natural therapies and cancer

A rational approach to helping cancer patients with natural therapies

Dr William Barnes MbChbBsc (otago)

FACNEM

chemotherapy success in cancer
Chemotherapy success in cancer
  • According to a recent analysis of 5 year surviaval rates in cancer patients following chemotherapy, oncology has done little to cure cancer . val
  • Chemotherapy as a stand alone treatment provided a 23% overall cure rate for adult solid tumours.

Ref:The contribution of cytoxic chemotherapy to 5 year survival in adult malignancies,

Morton. G.et al Clinical oncology (2004)16 ;549-

inflammation and cancer
Inflammation and cancer
  • Why is inflammation so important in cancer ?

Because it drives :

  • 1 mitosis
  • 2 metastasis
  • 3 angiogenesis
angiogenesis
angiogenesis
  • The process of neovasclarisation is controlled in normal tissues by a sequence of endogenous polypeptides that are secreted during growth, healing and tissue renewal.
  • Neoplasms are able to synthesize or induce some of these polypeptides.In particular Vascular endothelial growth factor (VEGF) and angiopoietins (APNS)
hypoxia
Hypoxia
  • All tumours have relative hypoxia, tumours outgrow their blood supply once they form masses greater than 1-2mm
  • Tumours do not grow progressively unless they induce blood supply from the surrounding stroma.
inflammation and cancer1
Inflammation and cancer
  • How:
  • Induction of cytokines :
  • NF Kappa
  • TNF alpha
  • Cox
  • Interleukins IL 1 IL6 IL 8
  • VEGF
  • NO
angiogenesis and inflammation
Angiogenesis and inflammation
  • Cytokines involved in induction of angiogenesis:
  • TNF alpha
  • Cox 2/ Lox
  • IL8
  • NOS
host derived factors
Host derived factors

Innate immune system cells such as macrophages (TAMS)produce cytokines :

  • NF Kappa , TNF alpha, NO, IL8.

Fibroblasts:

  • Producing, Fibroblast growth factor(FGF-1 and FGF-2 or bFGF) of which bFGF is the most potent.
source of drivers for angiogenesis
Source of drivers for angiogenesis

Tumour derived factors:

  • VEGF, anti angiopoietins are produced by hypoxic tumours
  • bFGF, Cox ,Lox, are up regulated genetically and screted by many tumours.ie; Squamous produces high levels of Cox and Lox.

Ca bowel is noted for Cox production

  • The tumour therefore can regulate its own rate of angiogenesis.
high expression of hifa is a predictor of outcome in pancreatic cancer
High Expression of HIFa is a predictor of outcome in pancreatic cancer
  • Hypoxic intrinsic factor ( HIF).is a signalling molecule that up regulates VEGF
radiotherapy
Radiotherapy
  • There is clear evidence whilst radiotherapy is a powerful antimitotic it also creates inflammation and as such angiogenesis:
  • During radiotherapy tumours increase there angiogenic potential.
  • Combination of antiangiogenic agents and radiotherapy is more effective:
  • AnsiauxR, Baudeletet al Clin Cancer Res 200511:743-50
  • Koukourakis MI et al anticancer Res 2001:21 4301-9
chemotherapy
Chemotherapy
  • “ NF KAPPA is a resistance factor to Platinum based Antineoplastic Drugs – new aproaches focusing on inhibition of this factor could help to minimize or even eliminate resistance to platinum drugs”
  • Vilma Maldonado Laguns and Jorge Melendez-Zajgla.
  • Hindawi Publishing Corporation
  • Metal Based Drugs Vol 2008
supporting the cancer patient
Supporting the cancer patient

A sensible program to provide support to the cancer patient should include treatments that suppress :

  • Angiogenesis
  • Mitosis
  • Metastatic spread

Deal with all of these 3 factors and results will be much better

nutritional substances
Nutritional substances
  • Overwhelming evidence exists in the literature showing that natural substances, in particular polyphenols, flavonoids, minerals and vitamins decrease, inflammation angiogenesis and metastasis by decreasing:
  • Cox ,Lox ,Nf kappa, IL1 ,IL8 ,TNF alpha, bFGF, VEGF .
genistein sensitises lymphoma to chop
Genistein sensitises lymphoma to CHOP
  • Vivo study : Diffuse large cell lymphoma which are notable for high expression of NK Kappa
  • High NF Kappa thought to increase the resistance of these cells to CHOP (cyclophosphamide, doxorubicin,vincristine, and prednisolone)
  • Genistein enhanced the growth inhibitory effects of the chemotherapy
  • Mol cancer ther 203Dec2(12):1361-8
inhibition of cell growth and vegf in ovarian cancer cells by flavonoids
Inhibition of cell growth and VEGF in ovarian cancer cells by flavonoids
  • In vitro study on OVCAR cells( ovarian Cancer)
  • Six flavonoids including: apigenin, luteolin, quercetin, genistein,and kaempferol were shown to inhibit cancer cell growth.
  • The rank of VEGF inhibition:
  • Genistein>kaempferol>apigenin>quercetin >luteolin>cysplatin.
  • Nutr cancer 2008:60(6):800-9
tamoxifen in oestrogen negative breast cancer
Tamoxifen in Oestrogen negative breast cancer
  • In vivo:
  • Realistic doses of Tamoxifen can suppress the growth of ER-negative breast cancer when combined with EGCG.
  • This is achieved by a decrease in mTOR ( a signalling molecule for angiogenesis) and EGF in the tumour
  • Br J Cancer 2008 Oct 7:99 (1056-63)
6 gingerol inhibits angiogenesis
6-Gingerol inhibits angiogenesis
  • In vitro and In vivo study;
  • study using melanoma cell line:
  • Anti-angiogenic activity was noted in vitro by inhibiting endothelial response to VEGF and bFGF.
  • In Vivo reduced numbers of lung metastasis were noted in treated animals.
  • Biochem Biophys Res Commun 2005Sep23;335(2):300-8
dose ranges of phytochemicals for angiogenesis inhibition
Dose Ranges of Phytochemicals for angiogenesis inhibition

Herb

Cancer adjuvant dose

1000-2500mg 3x daily

1000-2500mg 3x daily

600-1000mg 3xdaily

500-1500mg 3x daily

2000mg 3x daily

  • Curcumin
  • Green Tea
  • Grape seed extract
  • quercetin with bromelian
  • Silibinin
  • S.M Sagar MD D Yance MH and R.K.Wong MD
  • Current oncology – vol 13, Number 3
modified citrus pectin mcp
Modified citrus Pectin( MCP)
  • MCP is a fractionated pectin obtained from the peel and pulp of citrus fruits
  • MCP is rich in galactosides giving it affinity for certain types of cancer cells.
  • These galactosides bind to the surface galectins on the cancer cells
  • This bind stops metastatic cells from clumping and as such adhering to endothelial cells and developing as metastasis
  • Dose for clinical use 6 -30gms
mcp lead chelator
MCP Lead Chelator
  • MCP has been shown to chelate lead from children .
  • Trial involved children 5-12 with serum levels over 20micog/dL.
  • 15 gms 3x daily

..Dramatic reductions in serum lead were observed over one month .

  • This correlated with increases in urinary lead levels in 24 hr collections.
  • Altern ther health Med 2008 Jul-Aug ;14(6):18
suppression of proinflammatory responses by mcp
Suppression of proinflammatory responses by MCP
  • 2006 study on effects of MCP on Macrophage function.
  • Investigations of LPS activated macrophages expression of iNOS and COX-2 was conducted in vitro.
  • MCP reduced iNOS ,COX-2, and NF Kappa expression significantly.
  • Biochem Pharmacol 2006 Oct 168): 1001-9
oral mcp in breast carcinoma
Oral MCP in breast carcinoma
  • MCP given orally inhibits tumour growth angiogenesis and metastasis.i
  • in vivo
  • Studies in an athymic mouse model showed statistically reduced tumour growth and metastasis in mice given oral MCP
  • J Natl Cancer Inst 202 Dec 18;94(24:1854-62)
mcp cancer
MCP Cancer
  • MCP has been shown to reduce metastasis angiogenesis, and tumour growth in :
  • Colon , breast , melanoma, prostate, lung,in both primary and metastatic cancers.
vit d deficiency in breast cancer
Vit D deficiency in breast cancer
  • A Canadian study published in 2008 involving 512 women showed that 37.5% of women had Vit D lower than 50nmol/L at diagnosis. These women:

* had more aggressive disease

* were 93% more likely to develope metastasis

*were 73% more likely to die than women with normal levels of vit D at diagnosis.

In this country vit D deficiency particularly in the elderly may be an epidemic

Medscape medical news 26/5/08

vit d levels
Vit D levels
  • Vit D hydroxycalciferol nmol/L (50-150)
  • Mild deficiency 25-50 nmol/L
  • Mod deficiency 12.5-25 nmol/L
  • Severe deficincy <12.5 nmol/L
  • “Aus and NZ” MJA, 182(6): 281-285 2005
abcg2 the key to cancer resistance in cancer stem cells
ABCG2 : the key to cancer resistance in cancer stem cells
  • Multi-drug resistance remains one of the most common reasons for chemotherapy failure.
  • The membrane transporter proteinABCG2/BCRP1 has been shown to reduce the intracellular concentrations of chemotherapy drugs such as; ironotecan and doxorubicin.
  • ABCG2 may be represented in greater amounts in cancer stem cells.
abcg2 cont
ABCG2 cont
  • ABCG2 may underlie the ability of the cancer stem cell to start the regeneration of the tumour post chemotherapy.
  • Substances that inhibit ABCG2 may increase the chemosensitivity of cancer stem cells to chemotherapy and as such improve chemotherapy response;
  • An Y, Ongkeko WM, Expert Opin Drug Metab Toxicol Aug 27 2009
combined effects of flavonoids on abcg2
Combined effects of flavonoids on ABCG2
  • “ the added effects of multiple flavonoids for breast cancer resistant protein (ABCG2) inhibition .... Provides a rationale for using “flavonoid cocktails” as a potential aproach for multidrug resistance reversal in cancer treatment”
  • Zhang. S. et al ,Pharm Res 2004 Jul;21(7):1263-73
abc transporter abcg2 is inhibited by quercetin
ABC transporter ABCG2 is inhibited by Quercetin
  • “ 20 umol of Quercetin was found to be the strongest inhibitor of ABCG2 in an in vitro study in HEK293 cells.”
  • 20umol can be achieved with 100mg Quercetin
  • May need less if used in synergy with other flavonoids
  • Yoshikawa M, et al,J exp ther oncol 2004 Apr:4(1) :25-35