Peggy A Wright PhD, RD, CNS. Vision by Golubaja,

Transcription

1 Biology of Cancer Peggy A Wright PhD, RD, CNS Martin P Albert, MD Vision by Golubaja,

2 What is important to know about how cancer begins and grows Understand why and how to minimize cancer initiators Avoid mutagens Increase detoxification Increase antioxidant defenses Understand why and how to decrease crucial cancer promoters Maintain healthy weight Watch for insulin resistance and metabolic syndrome Avoid oxidative stress (smoking, nutrient poor diet) How and why to limit angiogenesis Understand what cancer stem cells are and why they are important Understand how you may be able to influence the expression of a tumor that tumors can spontaneously regress

3 Our Healthy Cell Contract The organism as a whole offers each cell protection and nutrients, exacting in return a promise of absolute obedience. Every cell is given a job and those jobs must be filled in their entirety not more or less than asked Any cell that fails to do its job sees its nutrients [and growth factors] withdrawn and its life terminated. Cancer breaks this contract. Nagourney, R

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5 Cancer stem cells are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving ii rise to new tumors. Cancer stem cells are found in almost all solid tumors and blood based cancers. STEM CELLS AND CANCER ONSET AND RECURRENCE

6 Normal stem cells Rare cells within organs with the ability to self renew and give rise to all types of cells within the organ to drive organogenesis Cancer stem cells Rarecells within tumors with the ability to self renew Rare cells within tumors with the ability to self renew and give rise to the phenotypically diverse tumor cell population to drive tumorigenesis

7 Cancer Stem Cells and Metastases By Malymajo (Own work) [CC BY SA 3.0 ( sa/3.0)], via Wikimedia Commons

8 Cancer Stem Cells and Relapse By Peter Znamenskiy (Own work) [Public domain], via Wikimedia Commons

9 Even early cancer appears to be a systemic disease Invasive tumors when discovered are often already systemic 5 cubic mm 1 billion cells Rare tumor cells found in blood and bone marrow even in localized disease (termed disseminated tumor cells, they are similar to breast cancer stem cells ) Clinical significance of these cells is not clear. We know how to look for the seeds, but we don t know how to assess the soil. Just because you plant a seed, doesn t mean that it is going to grow. (However, some tumors are like highly invasive weeds they are aggressive enough to grow even in poor soil. )

10 The Arrow of Cancer Moves in Both Directions i

11 Cancer Regression and Indolence Regression: Norwegian study using mammograms suggests that as many as 22% of invasive breast cancers resolve during a 5 year period. Raises the possibility that the natural course of some screendetected invasive breast cancers is to spontaneously regress. Indolence: Many men with prostate cancer never have symptoms, undergo no therapy, and eventually die of other unrelated causes. For example, up to 60% of men in their 60s who died of other causes had prostate cancer. Many factors, including genetics and diet, have been implicated din the development of prostate cancer.

12 Old versus New View of Cancer Old view Cancer is a linear process progressively progressively accumulating mutations until until it grows into a tumor which must be removed to prevent metastasis and death New view Early cancers may spontaneously regress Established cancers may remain dormant Changing the terrain may prevent progression, and contribute t to regression

13 Cancer is no more a disease of cells than a traffic jam is a disease of cars. A lifetime of studyof the internal combustion engine would not help anyone understand our traffic problems. Dr. D.W. Smithers 1962, Lancet

14 What explains the traffic jam? Terrain the microenvironment surrounding the cancer cells and the systems with which they interact

15 Three Keys to Cancer Prevention, Treatment, and Recurrence Prevention Eclectic Triphasic Medical System, Mederi Foundation, Donald R. Yance, MH, CN, RH (AHG)

16 Terrain Non Permissive Vitamin D Micronutrients High phytonutrients Botanicals 2 hydroxylated estrogens Exercise Meditation Social support Permissive Toxins High sugar/glycemic/ insulin/igf1 Micronutrient deficiencies Trans fats High copper/low zinc 4 hydroxylated estrogens Disturbed circadian rhythm (shift work) Helpless/hopeless Social isolation

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18 Acancer initiator is a chemical or substance that causes irreversible damage to the genotype [DNA] or phenotype of the cell [expression of the DNA]. INITIATORS

19 Types of cancer Initiators Reactive Oxygen Species (endogenous) Genotoxic hormone byproducts Xeno hormones (bisphenyl A, parabens) Toxic chemicals: organic solvents, pesticides, heavy metals (arsenic) UV light Radon Electromagnetic Fields (EMF) Oncoviruses: HPV, EBV, Hepatitis B & Hepatitis C Dietary cancer initiators: nitrosamines, heterocyclic amines (HCAs) andpolycyclic aromatic hydrocarbons (PAHs), trans fats

20 Reactive Oxygen Species (ROS) Oxidative Stress Michael P Murphy How mitochondri a produce reactive oxygen species. Biochem. J.: 2009, 417(1); PMID:

21 Oxidative Stress Antioxidants id t Prooxidants A i b l f i id t d/ di f i An imbalance favoring prooxidants and/or disfavoring antioxidants, potentially leading to damage -H. Sies

22 Estrogen Metabolites as Cancer Initiators The two most active estrogens estradiol and estrone are processed into other types of estrogens in our tissues (liver, uterus, breast tissue, fat cells). While some of these estrogens can promote cancer, other byproducts can become genotoxic. 4 hydroxy estrone can be transformed into a genotoxin unless it is successfully detoxified. It takes methyl groups from the B vitamin folic acid to detoxify this byproduct. Studies have found elevated levels of the estrogen byproduct, 4 hydroxy yestrone, to be elevated in the normal breast tissue of women diagnosed with breast cancer (the microenvironment). The body s manufacture of 4 hydroxyestrone y is affected partly by genetics and partly by environment (diet, environmental toxins).

23 The role of the vitamins B-12, folic acid, vitamin B-6 in detoxifying harmful estrogens Terrain factor in initiation: need for folic acid and methyl donors SAMe Folate acts as a methyl donor to help detoxify estrogen Harmful estrogens Detoxified estrogen 5 MTHF or methylfolate made from dietary or supplemental folic acid Activated B6 Goodman J E et al. Carcinogenesis 2001;22: Oxford University Press

24 Excess body fat and calories Excess insulin and blood sugar Excess inflammation and reactive oxygen species Excess hormonal influences PROMOTERS

25 Body Fat and Cancer Promotion Excess body fat increases CA Risk Central body fat secretes cytokines that promote inflammation Fat increases estrogen production Increase in body fat may impair immunity Too much body fat triggers insulin resistance, raising levels of insulin and growth factors that promote cancer and protect it from apoptosis (programmed cell death).

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27 Weight Gain Due to Treatment

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29 Insulin Like Growth Factor and Cancer Promotion BLOOD SUGAR AND INSULIN

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33 Mederi Foundation, Donald R. Yance, MH, CN, RH (AHG)

34 Mederi Foundation, Donald R. Yance, MH, CN, RH (AHG)

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37 Oncotype Dx Score, Metabolic Syndrome and Breast Cancer Oncotype Dx is a test on cancer ce tissue to determine if the cancer is likely to recur. Based on the total score, chemotherapy is either recommended or not. Oncotype Dx analyzes specific tumor cell proteins and receptors that make the tumor either more or less aggressive. This is the cancer cell. Women with low Oncotype Dxscores AND metabolic syndrome had much higher recurrence than expected. This is TERRAIN.

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40 INFLAMMATION

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44 Aggarwal 2013

45 Angiogenesis Hypercoagulation Migration and Metastases PROGRESSION

46 Migration & Metastases

47 What Is Tumor Angiogenesis? Small localized tumor Angiogenesis Tumor that can grow and spread Blood vessel Signaling molecule

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49 Coagulation and Cancer Progression The tendency towards excess blood coagulation is common in people with cancer. In cancer patients it leads to a higher incidence of blood clots (as in the veins of the legs). Excess blood coagulation is heightened by therapeutic interventions such as surgery or chemotherapy. Tumor cells have molecules on their surfaces that cause the blood to thicken and even clot the coagulation cascade. In addition, the proteins and other factors involved in clotting (tissue factor, thrombin, PDGF) stimulate tumor growth, angiogenesis and metastasis. Platelets, which help to form clots, become activated, adhere to tumor cells and facilitate tumor metastasis. Thus, persistent activation of the coagulation system makes the person more susceptible to developing cancer, and individuals with idiopathic venous thromboembolism (spontaneous blood clots in the leg) are at higher risk for developing cancer. [The terrain.]

50 IMMUNITY

51 Immune evasion and suppression The immune system successfully eliminates most potentially cancerous cells. If a tumor cell escapes identification it can go on to cause cancer. Such renegade tumor cells are no longer recognized by the immune system and are allowed to grow and divide. In addition, cancer cells: cloak themselves with fibrin to hide transform M1 macrophages into M2, which support, protect and feed them secrete many immunosuppressive compounds

52 Summary Initiation many factors Promotion Excess body weight and adipose (fat) tissue Glycemicoverload (sugar and insulin) Inflammation and oxidative stress Hormones and xenohormones Progression Angiogenesis Hypercoagulation Migration and metastases Immune system evasion

53 Terrain: helping to grow ourselves healthy and strong The Gardening Toolbox