Humans have two types of communication systems. These are the nervous system and the endocrine (hormone) system. These systems regulate body processes through chemical and electrical signals that pass between cells.

L-Tryptophan, Melatonin and DHEA :

I suspect that the presence of cancer is correlated with a disrupted brain wave function, and more specifically the delta brain wave function. I cannot tell for a fact whether the delta brain wave malfunction is a precursor to, or a result of cancer, but my research leads me to believe that delta brain energy malfunction has an effect on cancer progression.

Delta brain waves appear during the state of very deep sleep, relaxation or unconsciousness and measure between 0 - 4 Hz.

Delta brain waves provide a number of health benefits particularly for the healing, regenerating and strengthening of the body. They are involved with the production of 2 anti-aging hormones - melatonin and DHEA (Dehydroepiandrosterone). In addition, delta brain waves are believed to suppress the production of cortisol/adrenaline (the stress hormones). A disrupted, or inadequate, delta brain wave activity leads to depleted and unreplenished amounts of melatonin and/or DHEA, and unchecked/imbalanced amounts of cortisol. Untreated this condition leads to chronically low melatonin/DHEA, inability of the body to do its nightly repair functions on a cellular level and also higher amounts of cortisol in the blood.

Melatonin has a great anti-oxidant capacity, but also plays a huge functional role in keeping the cells' membranes fluid, which is very important for the health and physiology of the cells. Melatonin protects the cells' membranes from lipid peroxidation and also reduces the number of cholesterol receptors in the lipid layers of the cell membrane (very important function of melatonin).

I consider these hormones very important, if not crucial, in the successful recovery to health from cancer.

For information on delta brain wave you can refer to this article on the internet - http://brainwavewizard.com/entrainment/the-benefits-of-delta-brainwaves/

For information on how cancer can affect sleep duration and quality in both patients and caretakers you can refer to these in-depth resource articles :

How Cancer Treatment Affects Sleep (https://www.tuck.com/sleep-and-cancer/)

Better Sleep for Caregivers (https://www.tuck.com/why-caregivers-should-focus-on-sleep/)

When to Use a Medical Alert System (https://www.tuck.com/best-medical-alert-systems/)

For extra melatonin in your diet, eat organic tart cherries (they have the highest melatonin content) or drink organic tart cherries juice, walnuts, ginger root, bananas, oats and rice. Melatonin is also found in fenugreek, mint, lemon verbena, sage and red wine. Some of the medicinal plants that contain melatonin are - feverfew leaves (Tanacetum parthenium), St John's wort flowers and leaves (Hypericum perforatum) and Chinese skullcap roots (Scutellaria Baicalensis).

Melatonin is the end product of one of the Tryptophan pathways. Tryptohpan (L-Tryptophan) is an essential amino acid and has two metabolic pathways. One is L-Tryptophan, Serotonin, Melatonin and the other one is L-Tryptophan, Kynurenine, Niacin (B3).

Kynurenine is synthesized by the enzyme tryptophan dioxygenase , tryptophan-2,3-dioxygenase (TDO) , which is made primarily but not exclusively in the liver, and indoleamine 2,3-dioxygense (IDO), which is made in many tissues in response to immune activation. Kynurenine and its further breakdown products carry out diverse biological functions, including dilating blood vessels during inflammation and regulating the immune response. Some cancers increase kynurenine production, which increases tumor growth. Indoleamine-2,3-dioxygenase (IDO) is an intracellular heme-containing enzyme that initiates the first and rate-limiting step of tryptophan degradation along the kynurenine pathway. Most tumors express potentially immunogenic antigens to which the immune system can respond. In turn, the tumor-bearing host possesses high-avidity T cells that are specific to these antigens. And yet, in a phenomenon called immune tolerance, the host fails to reject the tumor. One of the ways that the tumors escape immune surveillance is by a process called immune tolerance. IDO exerts an immunosuppressive effect by facilitating immune escape of tumors.

Ethyl pyruvate and its analogue 2-acetamidoacrylate elicit a potent immune-based antitumor response through inhibition of indoleamine 2,3-dioxygenase (IDO), a key tolerogenic enzyme for many human tumors. Consistent with its reported ability to interfere with NF-kappaB function, ethyl pyruvate blocks IDO induction both in vitro and in vivo. Antitumor activity was achieved in mice with a noncytotoxic dosing regimen of ethyl pyruvate shown previously to protect against lethality from sepsis. Similar outcomes were obtained with the functional ethyl pyruvate analogue 2-acetamidoacrylate.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137353

George A. Bray; Frank L. Greenway (1999). "Current and Potential Drugs for Treatment of Obesity: Postabsorptive modifiers of nutrient metabolism". Endocrine Reviews. 20 (6): 805–87. doi:10.1210/er.20.6.805. PMID 10605627.

Adrographolide and galanal are two compounds isolated from the methanol extracts of Myoga, Zingiber mioga, or "Japanese ginger" flower buds significantly suppressed IDO1 activity. Galanal attenuated L-kynurenine formation with an IC₅₀ value of 7.7 µM .

St. John's Wort is a medicinal plant that has been investigated and confirmed as a natural TDO inhibitor.

IDO is activated by pro-inflammatory factors, e.g., interferon-gamma (IFNG), tumor necrosis factor-alpha, IL-1 beta, and lipopolysaccharide, while TDO is inducible by stress hormones, e.g., cortisol,etc.

ttps://www.researchgate.net/publication/315695557_Targeting_TDO_in_cancer_immunotherapy

Excellent article on melatonin:

http://journal.frontiersin.org/article/10.3389/fpls.2015.01230/full#B96

http://www.alternative-cancer-care.com/melatonin-meditation-and-cancer.html

The following is an article about one cancer patient's experience with tart cherries:

https://www.asbestos.com/blog/2011/10/19/red-tart-cherries-work-wonders-for-one-mesothelioma-patient/

DHEA is referred to as the "anti-aging hormone" and is produced in the adrenal glands. It is the only hormone to decline linearly with age in both sexes. Anyone over the age of 40 who does not supplement has already less than optimal levels of this hormone. Also be sure to make time for fun and joy activities as these actually help to boost DHEA and balance your hormones overall.

Example : My dad's DHEA level was that of a 93-year-old after my father had already been diagnosed for 4 months with cancer at the age of 57.

Shilajit -

It has been reported that Shilajit is the most powerful anti - aging substance and rejuvenator ever known to mankind. Feel the Power of Growing Young.

Shilajit helps with:
- increase in the core energy for sexual and spiritual power, hence commonly refered to as Indian Viagra.
- acceleration of protein and nuclei acid metabolism.
- regulating the blood sugar levels.
- counteracting diabetes.
- improving the function of the pancreas and strengthening digestion
- purifying of the blood.
- promotes the distribution of minerals into the bone and muscles.
- it improves restoration after exercise
- stimulates the immune system.
- also used as a counteract against fatigue.

Shilajit has been used for centuries by Ancient Indian yogis, and practitioners of Ayurvedic medicine. The natural habitat is in the Himalayan ranges. Shilajit is collected during the hot summer months when the ice has melted. It is available in the form of capsules on the market.

Shilajit means: "Rock-like" in Sanskrit - giving the indication that it will maker our bodies like a rock to withstand the ravages of aging.

Continued supplementation with purified shilajit for 90 days has shown to increase DHEA by 30 %, but also testosterone by 20% as well.

One of the places where you can purchase shilajit from is :

http://natreoninc.com/primavie-shilajit/

What is a hormone ?

According to Wikipedia: A hormone (from the Greek participle “ὁρμῶν”) is any member of a class of signaling molecules produced by glands in multi-cellular organisms that are transported by the circulatory system to target distant organs to regulate physiology and behavior.

Cholesterol is the precursor of all steroid hormones. "Chole" in Greek means "bile". Cholesterol is a lipid modified steroid molecule that is produced in the liver and is present in all animal cells, as it is a structural component of all animal cell membranes. Cholesterol's function is to maintain both membrane structural integrity and fluidity. In addition to its importance in cell structure, cholesterol is a precursor of steroid hormones - testosterone, progesterone, pregnenolone, androsterone, estrone, estradiol, cortisol, aldosterone and others; bile acid and vitamin D.

The summary of the following article states : " Novel sensors indicate how cell functions are affected by the distribution of cholesterol across the cell membrane. This information could lead to new methods for cancer detection."

The article also reads : "The team found that the amount of cholesterol on the inner side of the cell membrane was less than one-tenth of its amount on its outer side. They also found evidence that this asymmetry is maintained by the active transport of cholesterol from the inner part of the membrane to its outer part."

You can read the full article here:

https://www.sciencedaily.com/releases/2017/01/170120193650.htm

The endoplasmic reticulum (ER) serves as the major site of cholesterol synthesis. A class of cellular proteins named caveolins bind cholesterol at a 1:1 ratio and are involved in transport of de novo-synthesized cholesterol from the ER to the plasma membrane. Cellular homeostasis of cholesterol involves the regulation of its total cellular level and its distribution between membranes and within a given membrane.

Caveolin-1 (CAV1) is a membrane protein associated with cholesterol distribution, cell migration and signaling. Recent studies reveal that CAV1, which is altered in several cancer types, is involved in metabolic alterations with a focus on glycolysis, glutaminolysis, fatty acid metabolism, and autophagy. This leads to the adaptability of cancer cells and their increased potential for survival.

Bile acid synthesis occurs in liver cells which synthesize primary bile acids via cytochrome P450-mediated oxidation of cholesterol in a multi-step process. The rate-limiting step in synthesis is the addition of a hydroxyl group on position 7 of the steroid nucleus by the enzyme cholesterol 7 alpha-hydroxylase (CYP7A1 ). This enzyme is down-regulated by cholic acid, up-regulated by cholesterol and is inhibited by the actions of the ileal hormone FGF19.

Vitamin D refers to a group of fat-soluble steroids responsible for increasing intestinal absorption of calcium, magnesium, phosphate, zinc and multiple other biological effects. Vitamin D is not techincally a vitamin, instead it could be considered a hormone, with activation of the vitamin D pro-hormone resulting in the active form, calcitriol. Cholecalciferol is converted in the liver to calcifediol (25-hydroxycholecalciferol); ergocalciferol is converted to 25-hydroxyergocalciferol. These two vitamin D metabolites (called 25-hydroxyvitamin D or 25(OH)D) are measured in serum to determine a person's vitamin D status. Calcifediol is further hydroxylated by the kidneys to form calcitriol (also known as 1,25-dihydroxycholecalciferol), the biologically active form of vitamin D.

Calcitriol circulates as a hormone in the blood, having a major role regulating the concentration of calcium and phosphate , and promoting the healthy growth and remodeling of bone. Calcitriol also has other effects, including some on cell growth, neuromuscular and immune functions, and reduction of inflammation. Calcitriol increases the level of calcium (Ca²⁺) in the blood by increasing the uptake of calcium from the gut into the blood, increasing re-absorption of calcium by the kidneys, and possibly increasing the release of calcium into the blood from bone. Vitamin D3 -1,25(OH)₂D is a potent inhibitor of cellular proliferation and inducer of cell maturation.

Steroid hormones help control metabolism, inflammation, immune functions, salt and water balance, and the ability to withstand illness and injury.

The hormones adrenaline and cortisol are two stress hormones secreted by the adrenal glands sitting on top of your kidneys as a stress response mechanism. An environment of chronic stress can lead to adrenaline exhaustion - a condition that can trigger the development and progression of serious health conditions, including cancer.

See the article below:

 http://drpescatore.com/urgent-warning-that-sluggish-tired-all-the-time-feeling-may-be-putting-you-on-the-fast-track-to-deadly-disease

In a long-term stress response, the hypothalamus triggers the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. The adrenal cortex is stimulated by ACTH to release steroid hormones called corticosteroids. Corticosteroids turn on transcription of certain genes in the nuclei of target cells. They change enzyme concentrations in the cytoplasm and affect cellular metabolism.

There are two main corticosteroids: glucocorticoids, such as cortisol, and mineralocorticoids, such as aldosterone.

When the body and mind are in a long-term stress, glucocorticoids are the evolved bodily response to source and maintain a constant level of glucose for the brain's energy needs of neural functioning. The nervous system has a high requirement for glucose. The glucocorticoids mobilize lipid and protein reserves, stimulate gluconeogenesis, conserve glucose for use by neural tissue, and stimulate the conservation of salts and water. Glucocorticoids stimulate the synthesis of glucose and also have anti-inflammatory properties through inhibition of the immune system.
 

Mineralocorticoids regulate ion and water balance of the body by stimulating the kidneys to excrete less water and sodium ions in the urine.

Corticosteroids are key regulators of whole-body homeostasis and affect all of the major systems of the body, including the cardiovascular, musculoskeletal, nervous, and immune systems.

The central nervous system is the commander and chief of glucocorticoid responses, providing an excellent example of close integration between the nervous and endocrine systems.

Virtually any type of physical or mental stress results in elevation of cortisol concentrations in blood due to enhanced secretion of CRH in the hypothalamus.

Cortisol is synthesized from cholesterol and its secretion is suppressed by classical negative feedback loops. When blood concentrations rise above a certain theshold, cortisol inhibits CRH secretion from the hypothalamus, which turns off ACTH secretion, which leads to a turning off of cortisol secretion from the adrenal. The combination of positive and negative control on CRH secretion results in pulsatile secretion of cortisol. Typically, pulse amplitude and frequency are highest in the morning and lowest at night.

Mifepristone - (RU486) Glucocorticoid Receptor Antagonist - https://www.ncbi.nlm.nih.gov/pubmed/30952734

https://www.metaboliceffect.com/hormones-stress-cortisol/

Holy basil, or "Tulsi" (Ocimum sanctum) has potent anti-stress, anti-lipidemic, anti-diabetic and glycemic lowering properties.

Rooibos, Aspalathus linearis has a potent effect to reduce both cortisol and aldosterone in vivo.

Vitamin B6 ( pyridoxal-5-phosphate ) is a cortisol antagonist.

Melatonin inhibits cortisol production.

Pomegranate Extract reduces amount of salivary cortisol - http://www.endocrine-abstracts.org/ea/0034/ea0034P344.htm

Here are the targets of pomegranate for cancer chemoprevention and treatment: https://www.hindawi.com/journals/omcl/2015/938475/fig1/

You can buy Pomanox extract capsules from here:

https://www.elementa-ingredients.com/en/ingredient/pomanox-pomegranate-extract/

It is well established and proven in modern day medicine that prolonged exposure to corticosteroids can lead to insulin resistance and eventually to pre-diabetes condition with hyperglycemia. So, far we have made the connection and seen how prolonged physical or mental stress can lead to increased corticosteroids in your body and namely - cortisol and aldosterone. These corticosteroids in turn do damage to your metabolism by inducing insulin resistance and also increasing your blood glucose. So far, the end result is long-term chronic stress > prolonged state of increased corticosteroids - cortisol and aldosterone > developing insulin resistance and pre-diabetic levels of blood glucose.

Now what happens with fatty acid metabolism, when the blood glucose levels remain consistently (chronically) high. When the insulin concentration in the blood is high, the acetyl-CoA produced by glycolysis condenses as normal with oxaloacetate to form citrate in the mitochondrion. However, instead of continuing through the citric acid cycle to be converted to carbon dioxide and water, the citrate is removed from the mitochondrion into the cytoplasm. There it is cleaved by ATP citrate lyase (ACLY) into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to the mitochondrion as malate (and then converted back into oxaloacetate to transfer more acetyl-CoA out of the mitochondrion). This cytosolic acetyl-CoA can then be used to synthesize fatty acids through carboxylation by acetyl-CoA carboxylase into malonyl CoA, the first committed step in the synthesis of fatty acids. This conversion occurs primarily in the liver, adipose tissue and glands, where the fatty acids are combined with glycerol to form triglycerides, the major fuel reservoir of most animals. Fatty acids are also components of the phospholipids that make up the bulk of the lipid bilayers of all cellular membranes. ATP citrate lyase (ACLY) is a cytoplasmic enzyme activated by insulin which contributes to the synthesis of lipids and cholesterol inside the cells.

In the presence of ATP and Coenzyme A , citrate lyase (ACLY) catalyzes the cleavage of citrate to yield acetyl CoA, oxaloacetate, ADP, and orthophosphate:

citrate + ATP + CoA + H₂O → oxaloacetate + Acetyl-CoA + ADP + P_i

Increasing lines of evidence suggest that enzymes involved in lipid biogenesis play a significant role in cancer cell proliferation and progression. In many cancer types such as glioblastoma, colorectal cancer, breast cancer, non-small cell lung cancer, hepatocellular carcinoma etc., the level of ACLY has been found to be quite high as compared to normal cells. Cancer cell growth related to overexpression of ACLY can be inhibited by using chemical inhibitors or by the knockdown of ACLY gene.

Apart from ACLY, acyl-CoA synthetase short-chain family member 2 (ACSS2), is also an enzyme that produces acetyl-CoA using acetate as a substrate, and has also been established as promoting tumorogenesis.

Some studies have shown that cells that lack insulin or are insensitive to insulin overexpress Pyruvate dehydrogenase kinase  (PDK). As a result, the pyruvate formed from glycolysis cannot be oxidized which leads to hyperglycemia due to the fact that glucose in the blood cannot be used efficiently.

ACLY inhibitors - Hydroxycitrate

ACSS2 inhibitor - 1-(2,3-di(thiophen-2-yl)quinoxalin-6-yl)-3-(2-methoxyethyl)urea

Pyruvate Dehydrogenase Kinase (PDK) inhibitor - alpha-lipoic acid

As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models. This treatment, in combination with conventional chemotherapy, has yielded extremely encouraging results in glioblastoma, brain metastasis and lung cancer. Randomized trials are necessary to confirm these preliminary data. The major limitation is the fact that the combination of α-lipoic acid and hydroxycitrate can only be effective if the mitochondria are still present and/or functional. That may not be the case in the most aggressive tumors. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Concomitant correction of this alkalosis may be a very effective treatment in case of mitochondrial failure.

If you are facing a burden of cancer you should read the following article :

https://link.springer.com/article/10.1007%2Fs10637-012-9849-z

Most cancer cells use abnormal metabolism to generate energy. Cancer cells upregulate glycolysis and lactic acid fermentation in the cytosol and prevent mitochondria from completing normal aerobic respiration. Instead of completely oxidizing glucose to produce as much ATP as possible, cancer cells would rather convert pyruvate into the building blocks for more cells. In fact, the low ATP:ADP ratio caused by this effect likely contributes to the deactivation of mitochondria.

Here comes the question what in the first place makes the cells suddenly switch from aerobic respiration energy mode to an anaerobic glycolytic energy mode ? Could this be triggered by a signalling molecule, by a change in the pH of the cell, by a change in the cellular membrane's permeability, by a change in the electrical potential of the cell ?

The synthesis of ATP from ADP and P_i, driven by the transfer of electrons from NADH or FADH₂ to O₂, is the major source of ATP in aerobic nonphotosynthetic cells. Much evidence shows that in mitochondria and bacteria this process, called oxidative phosphorylation, depends on generation of an electro-chemical proton gradient (i.e., proton-motive force) across the inner membrane, with electron transport, proton pumping, and ATP formation occurring simultaneously. In the laboratory, for instance, addition of O₂ and an oxidizable substrate such as pyruvate or succinate to isolated intact mitochondria results in a net synthesis of ATP if the inner mitochondrial membrane is intact. In the presence of minute amounts of detergents that make the membrane leaky, the oxidation of these metabolites by O₂ still occurs, but no ATP is made. To phosphorylate ADP, protons enter the ATP synthase complex from the region between the inner and outer membranes of the mitochondria. The process of protons entering the proton channel of the F0 portion of the enzyme creates energy to power the process of adding a phosphate group to ADP by the F1-ATPase portion. Under these conditions, no transmembrane proton concentration gradient or membrane electric potential can be maintained.

The electron transport chain is responsible for establishing a pH and electro-chemical gradient that facilitates the production of ATP. It appears that this electron transport chain's proper functioning is dependent on the healthy state of the inner mitochondrial membrane.

There are a number of targets that aim at the glycolytic pathway of cancer progression. One needs to be very careful to make sure the targeted items affect mainly, if not mostly, only cancer cells.

Glucose is a major source of energy in cancer cells that generates ATP almost through glycolysis, a far less efficient energy generator than mitochondrial respiration. As the survival of cancer cells predominantly depend on the high rate of glucose consumption and elevated glycolysis, targeting the Warburg effect and glucose metabolism has become an important strategy for cancer therapy. Several factors, including mitochondrial defects, oncogenic stimuli, hypoxia, and aberrantly enhanced expression of glycolytic enzymes, are now considered to be important drivers of the Warburg effect. Due to their critical role in cancer cells, these glucose metabolism-related proteins and enzymes are believed to be potential targets for drug design and cancer therapy. There are two main strategies under investigation that target glucose metabolism. One focuses on the regulation of glycolytic flux-related proteins including Gluts, MCTs, lactate dehydrogenase A (LDHA), HK2, and PKM2. This strategy aims to directly regulate the glucose supply and glycolytic pathways to control the energy production in cancer cells. Another strategy focuses on factors believed to be central for metabolic regulation, including HIF-1a, c-Myc, AKT, mTOR, and AMPK. These factors control the abundance of proteins that regulate the glucose and energy supply of cancer cells. Several compounds, including rapamycin, berberine, and metformin, have been shown to regulate glucose metabolism and exhibit anticancer activities.

- A diagram of the glycolytic pathways

https://en.wikipedia.org/wiki/Tumor_hypoxia#/media/File:HIF-1_Glycolytic_Pathway.png

- An Excellent Article on Glycolytic Pathways - https://www.hindawi.com/journals/ijcb/2013/639401/

Apigenin - a potent inhibitor of the glycolytic pathway. It can be purchased as a supplement or is available in chamomile tea.

Bitter Melon  (Momordica charantia) is a very good means to control glucose levels and also treat cancer. You can juice bitter gourd (bitter melon) or take it in a supplment form, or as a tea.

Oridonin is an active diterpenoid isolated from Rabdosia rubescens "Dong Ling Cao" in the 1970s that has potent anti-tumor activities in many types of human cancer both in vitro and in vivo. Oridonin treatment had multiple effects such as inhibition of proliferation and induction of cell cycle arrest, apoptotic and autophagic pathways in a variety of cancer cells including those of colorectal carcinoma. Previous studies have indicated that various factors, including Akt, ERK, FAS, ROS, NF-κB, PI3K, and RTK, were involved in the anticancer activity of oridonin.

The role of unresolved infections and chronic inflammation in the development of cancer is undisputed and I would not go into too many details. There is already enough information on the internet that addresses the links between pathogens, infections, inflammation and cancer.

Recently, several studies have demonstrated the ability of natural product derivatives to inhibit mucin over-expression in various cancerous tissues in vitro and organ systems in vivo.

Guggulsterone

Gum Guggul derived from the bark of the plant Commiphora wightii is used from centuries to treat various inflammation associated diseases like hypercholesterolemia, atherosclerosis, rheumatism, and obesity. The crude ethyl acetate extract of gum guggul has been shown to suppress inflammatory mediators such as IFN-γ, IL-12, TNF-α and IL-1β. Recently, Guggulsterone E and Guggulsterone Z the active components from the gum guggul has been shown to exhibit anti-inflammatory activities by suppressing cytokines expression and inhibit tumor growth both in vitro and in vivo by modulating numerous survival and proapototic signaling cascades. By affecting growth factors, growth factor receptors and several transcription factors implicated in inflammation like NF-κB, STAT1/3, C/EBPα, androgen and glucocorticoid receptors, guggulsterone (GS) modulates the expression of antiapoptotic proteins (IAP1, XIAP, Bcl-2, cFLIP, survivin), inhibits cell survival, cell proliferation associated proteins (cyclin D1, c-Myc), abrogates angiogenesis, and metastasis (MMP-9, COX-2, VEGF) in tumor cells. GS has also been demonstrated to inhibit the transcriptional regulator farnesoid X receptor (FXR) and is involved in maintaining cholesterol/bile acid homeostasis, triglyceride and glucose metabolism.

Gambogic Acid - target (NF-kB) the main component derived from the fruit of Garcinia indica or Garcinia Hanburyi, used in Indian cuisine as a spice, suppressed inflammation and carcinogenesis in a wide number of various cancers. It has been tested in animal studies with great success, but not in human studies.

Methyl Jasmonate - targets (HK2, and EZH2, ARID1A) disrupts quite successfully the glycolytic pathway of cancer metabolism and contributes to cancer cells' apoptosis.

Treatment with it is not approved yet, but it can be purchased and used with a nebulizer at very small doses - http://www.methyljasmonate.com

This is a publication that addresses the roles of viruses, bacteria and pathogens in carcinogenesis:

https://www.cancer.org/cancer/cancer-causes/infectious-agents/infections-that-can-lead-to-cancer/viruses.html

ROLE OF IL-22

The IL-22/IL22R expression pattern makes IL-22 an important cytokine mediating the cross-talk between leucocytes and epithelia, particularly at barrier surfaces. Indeed, IL-22 is critical in reinforcing innate immune defences of epithelial cells in gut and lung infectious models. IL-22 is also important in the promotion of tissue repair. Nevertheless, numerous studies have also demonstrated that IL-22 can be a potent inducer of pathological inflammation. Indeed, IL-22 can promote tissue inflammation and self-destruction and is involved in the pathophysiology of several immune-mediated inflammatory diseases, such as psoriasis and rheumatoid arthritis. These paradoxical effects of IL-22 are dependent on the context of IL-22 production, as IL-22 can synergistically act with other inflammatory cytokines, including IL-17 and tumor necrosis factor-α. A tight regulation of the IL-22/IL-22R axis appears therefore critical in maintaining the beneficial effects of IL-22 and avoiding deleterious inflammatory effects.

IL-22BP inhibits IL-22 biological effects and is expressed in secondary lymphoid organs (SLO), breast, and epithelial tissues, such as gut, lung, and skin. IL-22BP acts as a natural regulator of IL-22, preventing exaggerated effects of the cytokine.

ARYL HYDROCARBON RECEPTOR (AhR)

The aryl hydrocarbon receptor (AhR or AHR or ahr or ahR) is a protein that in humans is encoded by the AHR gene. The aryl hydrocarbon receptor is a ligand-activated transcription factor involved in the regulation of biological responses to planar aromatic hydrocarbons. This receptor has been shown to regulate xenobiotic-metabolizing enzymes such as cytochrome P450.

AHR binds several exogenous ligands such as natural plant flavonoids, polyphenolics and indoles, as well as synthetic polycyclic aromatic hydrocarbons . AhR is a cytosolic transcription factor that is normally inactive.

AhR can directly regulate IL-22 gene expression and cytokine production . AhR is found in the cytoplasm complexed with heat shock protein 90, and once activated, the AhR complex can translocate to the nucleus where AhR can act as a transcription factor. Various ligands, physical stress, cyclic AMP, and calcium (Ca²⁺) can all activate AhR.

Since its first description in 2000, the actions of IL-22 in mediating the cross-talk between the immune and epithelial systems were extensively described. By its ability to reinforce innate immunity of epithelial cells, notably by inducing antimicrobial peptide production, IL-22 has been demonstrated to be crucial in the resolution of gut and lung infections. Combined with the capacity of IL-22 to promote tissue repair in several inflammatory conditions, IL-22 properties seem necessary in the maintenance of tissue homeostasis.

However, excessive actions of IL-22 may be particularly deleterious for epithelial tissues, suggesting that IL-22 needs to be tightly regulated to prevent unwarranted tissue damage and dysregulated epithelial cell proliferation. This regulation may be partly achieved by IL-22BP, given its specific inhibitory properties on IL-22 actions. Our study strongly suggests that the natural production of IL-22BP, observed in SLO and epithelial tissues, may be principally achieved by a subset of cDCs. cDCs may produce high levels of IL-22BP at physiological state, when IL-22 actions are not desired, then, depending on the stimuli, IL-22BP production could be further enhanced or stopped.

Maintenance of gut homeostasis is complex and implicates the establishment of equilibrium between the host and the commensal microbiota, while maintaining the ability to fight against invading pathogens. The gut immune system has an important role in this equilibrium and needs to be tightly regulated to avoid unbalanced reactions leading to inflammatory bowel diseases. Regulation of inflammatory cytokine production is also crucial in the maintenance of gut homeostasis.

In conclusion, our study identified a subset of immature cDCs as a constitutive source of IL-22BP in the steady state in SLO and gut. Together with the recent report from Huber et al., these data strongly suggest that DC-produced IL-22BP has an important role in controlling IL-22 effect on epithelial cells. Moreover, our study suggests that the regulation of IL-22 by IL-22BP in the gut could be enhanced by RA.

Retinoic acid (RA) is a morphogen derived from retinol (vitamin A) that plays important roles in cell growth, differentiation, and organogenesis.

Vitamin A is commonly known as the anti-infective vitamin and has an essential role in vision and cellular differentiation, the latter providing a unique core mechanism helping to explain the influence of vitamin A on epithelial barriers. Alterations in the epithelial lining of vital organs occur early in deficiency, suggesting a potentially important role for the barrier function.

Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels. In order to reach critical mass and continue their growth tumor cells need their own blood supply. To achieve this a number of signalling cellular pathways are up-regulated.

Fibroblast growth factors, or FGFs, are a family of growth factors, with members involved in angiogenesis, wound healing, embryonic development and various endocrine signaling pathways. One important function of FGF1 and FGF2 is the promotion of endothelial cell proliferation and the physical organization of endothelial cells into tube-like structures. They thus promote angiogenesis, the growth of new blood vessels from the pre-existing vasculature. FGF1 and FGF2 are more potent angiogenic factors than vascular endothelial growth factor (VEGF) or platelet-derived growth factor (PDGF).

More than a dozen different proteins have been identified as angiogenic activators, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin, transforming growth factor (TGF)-α, TGF-β, tumor necrosis factor (TNF)-α, platelet-derived endothelial growth factor, granulocyte colony-stimulating factor, placental growth factor, interleukin-8, hepatocyte growth factor, and epidermal growth factor.

The prevention of new blood supply formation for the tumor is critical and can be achieved with a few supplements. Among these are grape seed extract, coral calcium, green tea (ECGC), sanguinarine, etc.

Paclitaxel - taxanes are well-recognized naturally occurring anti-cancer drugs; they are originally isolated from the Pacific Yew tree (Taxus brevifolia) and kill tumor cells by interfering with their mitotic tubulin spindle. During the last decade, taxol was found to possess very potent anti-angiogenic activity with much lower doses than its cytotoxic dose. Metronomic therapy (continuous treatment with very much lower dosing) with taxol induced promising anti-angiogenic effects and overall clinical anti-tumor response.

Vascular Targeting Agents -

Combretastatin A-4 (CA-4) is a natural product, which was first isolated from the bark of the South African tree Combretum caffrum. The bark, leaves and roots of Combretum caffrum are commonly sold on local markets throughout South Africa. In South Africa a formulation made from a bark decoction is produced commercially and sold as an anti-cancer remedy. Combretum caffrum bark can be purchased on the internet at US$ 22 per 100 g.

Seh-haw or Kinkeliba tea (Combretum micranthum)

www.kinkeliba.net http://www.kinkeliba.net

Tumor hypoxia is the condition where tumor cells have been deprived of oxygen. As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. In order to support continuous growth and proliferation in challenging hypoxic environments, cancer cells are found to alter their metabolism. Furthermore, hypoxia is known to change cell behavior and is associated with extracellular matrix remodeling and increased migratory and metastatic behavior.

Tumor hypoxia leads to advanced, but dysfunctional vascularization and acquisition of epithelial-to-mesenchymal transition phenotype resulting in cell mobility and metastasis. Hypoxia alters cancer cell metabolism and contributes to therapy resistance by inducing cell quiescence. Hypoxia stimulates a complex cell signaling network in cancer cells, including the HIF, PI3K, MAPK, and NFĸB pathways, which interact with each other causing positive and negative feedback loops and enhancing or diminishing hypoxic effects.

Oxygen concentration in humans ranges between approximately 9.5% O₂ in the renal cortex to 4.6% O₂ in the brain with neurons extremely sensitive to hypoxia and it is almost lower by 50% in tumor tissue compared to normal tissue.

HIFs contribute to the glycolisis pathway.

Hyper-baric Oxygen Chamber (HBOT) - one way to combat tumor hypoxia is with a hyperbaric oxygen chamber treatments. The saturation of the cells and tissues with Oxygen is achieved at adequate levels to provide for an unfavorable cancer terrain, but also to heal damaged tissue.

Pine needle oil - Pinus sylvestris oil - when used in small quantities in a vaporizer or air-humidifier can successfully enhance tissue oxygenation.

L-Arginine & L-Citrulline- can repair mitochondrial disfunction, combat lactic acidosis and increase NO production. L-Arginine plays an important role in cell division, the healing of wounds, removing ammonia from the body, immune function, and the release of hormones. L-Arginine increases the flow of nutrients and oxygen to tissues in our bodies.

https://www.youtube.com/watch?v=_Xmt2QPCUZ4

Cocoa Powder - (Zinc, Magnesium and Selenium) - are minerals that increase the oxygen carrying quality and capacity of hemoglobin and have also co-enzyme functions that are related to energy production - ATP.

Saffron Extract- (Crocus sativus L.) has showed to induce apoptosis in a multiple cancer cell lines and increase the life-span of tested subjects by 2-3 fold. Saffron has allegedly the ability to normalize the albumin to globulin ratio in cancer patients, which is very important.

An interesting article that connects HIF-1alpha with PDK1 and glycolysis :

https://www.nature.com/articles/ncomms11635

Garlic - Organic Sulfur - for acetyl-CoA synthesis

http://www.naturalhealth365.com/0886_sulfur_cancer.html/

Damage to DNA can render a cell useless, or even harmful to an organism. Apoptosis, or programmed cell death, evolved as a rapid and irreversible process to efficiently eliminate dysfunctional cells. A hallmark of cancer is the ability of malignant cells to evade apoptosis. P53 is an extremely important protein. Amongst its many functions, it is responsible for detecting DNA damage, chromosome abnormalities and arresting the cell cycle to initiate repair; if repair is not possible then apoptosis is induced. P53 induces apoptosis by increasing the production of the pro-apoptotic protein Bax. Bax stimulates the mitochondria to release cytochrome c, which activates the caspase cascade which ultimately results in cell suicide. P53 is vital for maintaining the integrity of our genome at the most fundamental level. So how do cancer cells escape death? The most common method is the loss of the apoptosis gatekeeper, the protein P53. More than half of all types of human cancers have a mutated or missing gene for P53, resulting in a damaged or missing P53 protein. As an alternative to achieving the loss of P53, cancer cells can compromise the activity of P53 by increasing the inhibitors of P53, or silencing the activators of P53.

The activation of p53 tumour suppressor gene leads to an increase in mitochondrial respiratory activity and decrease in glycolysis. Loss of p53 function actually downregulates the expression of gene encoding the synthesis
of cytochrome c oxidase 2, the product of which is required for the assembly of
cytochrome c oxidase of the mitochondrial respiratory chain. Therefore, mutations in p53 can suppress mitochondrial respiration as a result of cytochrome c oxidase deficiency and facilitate the shift of cellular energetic metabolism towards glycolysis.

Scutellaria baicalensis shows increased expression of p53 in the cancer cells of key proteins related to the enhancement of apoptosis is observed . Similarly, Gleditsia sinensis thorns are used as a medicinal herb, which shows a decrease in cell growth and an increase in cell cycle arrest during the G2/M-phase. The arrest is correlated with increased p53 levels . The mRNA level of the wild-type p53 gene also increases with the treatment of Kanglaite, an extract from Coix seed. It can be assumed that Kanglaite extends half-life of p53 protein, by which Kanglaite may induce the apoptosis of tumor cell. A Ginsenoside, one of components in American ginseng herb, increases levels of Bax protein and induces cell death, activating the p53 tumor suppressor . Knockout of p53 dramatically decreases the cell death, suggesting that p53 contributes to apoptosis induced by Ginsenoside in the cancer cells. Thymoquinone, the most abundant component in black seed, is a dietary chemopreventive agent against cancer. Apoptosis induction by thymoquinone is associated with an increased p53 mRNA expression and the downstream p53 target genes.

Medicinal mushrooms have apoptosis inducing qualities to cancer cells. These fungi species are Cordyceps, Ganoderma species, Coriolus versicolor and Hypsizygus marmoreus.

Curcumin - found in turmeric promotes the expression of TP53.

Capsaicin - found in red chili peppers induces apoptosis in a number of different cancer cell lines through the activation and expression of TP53.

NAD is the sole substrate for PARP enzymes involved in DNA repair activity in response to DNA strand breaks; thus, NAD is critical for genome stability. Several studies, mostly using in vitro and animal models, suggest a possible role for niacin in cancer prevention. Nevertheless, large studies are needed to investigate the association between niacin deficiency and cancer risk in human populations.

"Thunder God Vine" (Tripterygium Wilfordii) Extract

Niagen - a supplement proved to boost NAD+ levels in patients

The work of Prof. Mirko Beljanski has focused on researching the DNA of normal cells and cancer cells and as a result finding natural extracts such as Pao pereira, Rauwolfia vomitoria, Golden leaf of Ginkgo Biloba that can attack selectively cancer cells and be non-toxic to normal cells.

HDAC Inhibitors - Valproic Acid, Sodium Byturate

https://www.omicsonline.org/open-access/anticonvulsant-drug-valproic-acid-in-cancers-and-in-combination-anti-cancer-therapeutics-2329-6798.1000118.php?aid=24583

Galectin-1 and Galectin-3 are causing metastasis.

Modified citrus pectin (MCP) is a natural inhibitor of Galectin-3 and also heavy metal chelators in breast and prostate cancer. The more popular brand is MCP (PectaSol®) alone or as an MCP/alginate combination (PectaSol® Chelation Complex™). The usual daily dose is 5grams of powder 3 times a day.

AVEMAR (FWGE) - fermented wheat germ extract which slows the progression of tumor development and extends survival by targeting a number of critical enzymes and pathways of cancer. It also successfully combats cachexia (muscle wasting).

BioBran (MGN-3) -Non-toxic arabynoxylan food supplement (or functional food) made from breaking down rice bran with enzymes from the Shitake mushroom. It has been clinically proven to help powerfully enhance depleted immune systems, making it an ideal food supplement for those with immune systems compromised by disease and/or toxic treatments.

Guar gum (seeds from Cyamopsis tetragonoloba) also has similar effects.

If you are experiencing muscle wasting, also known as cachexia - which is life threatening and the main reason for cancer morbidity, I recommend reading the following article and paying particular attention to Part 4 :

https://www.drlam.com/blog/catabolic-state-adrenal-fatigue-part-1/11116/

Recent Clinical Trials -

Atorvastatin - is an inexpensive drug widely used to control cholesterol.

https://medicalxpress.com/news/2019-03-drug-cholesterol-effective-cancer-associated-cachexia.html

Espindolol - 10mg twice daily

https://patents.google.com/patent/CA2671622A1/en

https://www.jamda.com/article/S1525-8610(14)00588-X/fulltext

Most, if not all, cancer patients have increased serum ammonia levels, due to the glycolysis metabolism. Long term ammonia in the blood can become pretty toxic and can have detrimental impact on one's health. This can easily be tested as a lab test by your oncologist, yet most oncologist do not include that in their patients' blood work panels. You may even be asked by your oncologist - "Ammonia ? Why do you need that test? " Anyway, you need to bind that ammonia and get it out of your body if you intend to live long term, as in greater than a year or two.

glutamate + H₂O + NADP⁺ → α-ketoglutarate + NADPH + NH₃ + H⁺

Lactulose - has been proven useful to bind ammonia and reduce the serum level in cancer patients.

L-Arginine - converts in the body to L-Ornithine and also binds ammonia and can be useful in that regard.

Wheat-grass juice & Chlorella - have the ability to bind ammonia and excrete it out of the body and also oxygenate the blood.

Sigma-1 receptors ubiquitously express in several organs of mammals including brain, liver, pancreas, testis, overlay, placenta, and adrenal gland, as well as in malignant tumors. A number of studies using selective sigma receptor ligands have demonstrated that sigma-1 receptors are involved in regulations of morphogenesis of neuronal cells (e.g., synaptogenesis, neuronal differentiation, myelination), neuroprotection, pain, pathophysiology of certain human diseases including depression, drug abuse, Alzheimer’s disease and cancer.

Since the 1970 s, a numerous number of studies have demonstrated a variety of pharmacological and physiological effects of sigma-1 receptors and their ligands in both in vitro and in vivo systems; that include neuroprotection, anti/pro-apoptotic action, cellular differentiation, potentiation of Ca2+ signalling via IP3 receptors, regulation of ion channels such as K+ channel and NMDA receptor, potentiation of trophic factor signalling (NGF, EGF, BDNF and MAPKs), cellular proliferation, protein secretion, carcinogenesis, long-term potentiation of hippocampal neurons, learning and memory, mood and cognition, and drug-dependence and craving . Sigma-1 receptors forming the complex with BiP are basically at the dormant state, thus minimizing the chaperone activity. The depletion of ER Ca2+ by activation of IP3 receptors or inhibition of the ER Ca2+ pump by thapsigargin triggers the dissociation of sigma-1 receptors from BiP, which in turn fully activates sigma-1 receptor chaperones.

Early binding studies found that sigma-1 receptors highly express in many cancer cells . Recent studies demonstrated that some sigma-1 receptor ligands inhibit unstrained proliferation of carcinoma both in vitro and in vivo. A recent study provides an intriguing mechanism of sigma-1 receptors in regulating proliferation in cancers. The study found that sigma-1 receptor ligands cause the dissociation of cholesterol from sigma-1 receptors, which subsequently leads to reconstitution of plasma membrane rafts . The reconstitution of lipid rafts promotes dramatic inhibition of cell adhesion mediated by β-integrin, the strength is indicative of invasiveness of cancers. Knockdown of sigma-1 receptors by siRNA shows the similar phenotype. The effect of sigma-1 receptor ligands was abolished if the composition of lipid rafts is altered by using drugs that affect lipid raft formation such as methyl- β-cyclodextrin. These findings further suggest that cholesterol trafficking and raft formation regulated by sigma-1 receptors may be involved in promoting pathogenic processes involved in human diseases.

The sigma-1 receptor (Sig1R) is a membrane protein that has been involved in many cellular processes. Sig1R is in fact a stress-activated chaperone mainly associated with the ER-mitochondria interface that can regulate cell survival through the control of calcium homeostasis. Sig1R functionally regulates ion channels belonging to various molecular families and it has thus been involved in neuronal plasticity and central nervous system diseases. Interestingly, Sig1R is frequently expressed in tumors but its function in cancer has not been yet clarified.

Sig1Rs have been associated with many diseases including stroke, cocaine addiction, Alzheimer's disease, amnesia, amyotrophic lateral sclerosis, retinal degeneration, and cancer. Sig1R is mainly located at the ER, in close contact with the mitochondria, in the so-called mitochondria-associated-ER membrane domains (MAM). In resting condition, Sig1R resides in ceramide- and cholesterol-rich lipid microdomains associated with the ER-resident chaperone GRP78 (BiP) . Under cellular stress leading to ER injury, Sig1R dissociates from BiP and binds IP₃ receptors, enhancing in turn cell survival through the control of calcium signaling between the ER and mitochondria. In addition, Sig1R translocates to other cell compartments and binds to different membrane proteins. The stimulation with sigma “agonists” mimicks stress-induced Sig1R dissociation from BiP and Sig1R delocalization, while sigma ligands classified as “antagonists” impede this process. Altogether, these results have led to a model in which Sig1R is “silent” in normal physiological conditions, whereas in case of a disease, Sig1R behaves as a chaperone that binds client protein to the benefit of cell survival. This exciting hypothesis has been validated by recent studies demonstrating that Sig1R molecular silencing reduces brain recovery after experimental stroke (Ruscher et al., 2011) and promotes retina degeneration after acute damage to the optic nerve (Mavlyutov et al., 2011).

Sig1R may participate in the electrical remodeling of cancer cell electrical properties to enhance their survival and aggressiveness.

Altogether, studies strongly suggest that Sig1R is over expressed in many cancer cells and an extensive exploration of Sig1R expression in biopsies from various cancers is now required to determine whether Sig1R could be proposed as a diagnosis or prognosis marker.

Sig1R is a stress-activated chaperone which controls, through different mechanisms, several families of ion channels at the plasma membrane and at the MAM. Studies realized in the retina, brain and heart strongly suggest that Sig1R participates in cell resistance to tissue injury. Several reports indicate that Sig1R exerts a role only in conditions of stress and remains generally “silent” in healthy organs or in steady-state conditions . Thus, it is tempting to speculate that tumor cells hijack the primary protective function of Sig1R to enhance their survival/growing/invasive potency in restrictive metabolic conditions encountered within the tumor tissue. As demonstrated by many authors, the aberrant expression of ion channels confers selective advantages for cancer cells to adapt their behavior and survival in the tumor environment. While research studies mainly focus on the function of one ion channel in a cancer type, it is important to consider that many ion channels are deregulated in the same cancer cell. Because a variety of ion channels are client proteins for Sig1R, it is speculated that the Sig1R chaperone controls cancer cells' electrical plasticity by “driving” ion channels to potentiate their function in proliferation, apoptosis resistance, migration and angiogenesis. At the time being, there is no real explanation on the process that controls the expression of all these ion channels in cancer cells and it is often postulated that this is due to the acquisition of an embryonic or developmental phenotype. The possibility that Sig1R expression might participate to this phenotype is an interesting hypothesis that has not been explored so far.

It is noteworthy that ion channels expressed in cancer cells play important functions in healthy organs as well such as in the heart and brain. As a consequence, therapies based on toxins and drugs directly targeting ion channels present major drawbacks for cancer treatment.

The MAM is known to play a role as a center that directly provides Ca²⁺ or phospholipids to the mitochondria. Ca²⁺ provided by MAM-localized IP₃ receptors activates the TCA cycle, thus causing ATP production . One of proven mechanisms of the sigma-1 receptor is to stabilize IP₃ receptors at the MAM for proper Ca²⁺ flux from the MAM into mitochondria.

It has been suggested that defective cholesterol exportation out of the cells appears to be a key component in a variety of cancers. The proper function of ABCA1 is critical for sensing cellular stress. If ABCA1 function is lost in cancer cells, cholesterol builds up in the cell's mitochondria and makes their membranes more rigid (less fluid). This is turn inhibits the function of cell-death triggers that normally become activated in response to cell stress. Thus, when functioning properly, ABCA1 has anti-cancer activity, by keeping mitochondrial cholesterol low it protects the functioning of the cellular stress response systems and acts as a barrier to tumor formation and progression. It was demonstrated that some of the relatively rare ABCA1 mutations found in human colon cancer disabled the gene's ability to export cholesterol. And by re-establishing the cholesterol export function in human colon cancer cells, they inhibited the cells' ability to grow as cancers when grafted onto mice.

Retinoic acids - Retinoic acids regulate the reverse cholesterol transport by inducing the ATP binding cassette transporter A1 (ABCA1) dependent cholesterol efflux in macrophages, neuronal as well as intestine cells. Treatment with ATRA dramatically up-regulated ABCA1 expression in CD4+ T cells in a time and dose dependent manner. The expression of ABCA1 paralleled with increased ABCA1-dependent cholesterol efflux. TRA up-regulates ABCA1 expression and cholesterol efflux in CD4+ T cells and combination of ATRA and liver X receptor (LXR) agonist further enhanced these effects.

Bafilomycin - In vivo bafilomycin reduced average tumor volume in MCF-7 and MDA-MB-231 xenograft mouse models by 50% and did not show toxic effects at a dosing of 1 mg/kg. Additionally, when combined with sorafenib, bafilomycin also caused tumor regression in MDA-MB-231 xenograft mice. In a HepG2 orthotropic HCC xenograft model in nude mice, bafilomycin prevented tumor growth.^[3]

https://www.ahajournals.org/doi/full/10.1161/atvbaha.114.305182

Oxysterols - Cephalostatin 1, OSW-1, ritterazine B and schweinfurthin A are natural products that potently, and in some cases selectively, inhibit the growth of cultured human cancer cell lines. The cellular targets of these small molecules have yet to be identified. We have discovered that these molecules target oxysterol binding protein (OSBP) and its closest paralog, OSBP-related protein 4L (ORP4L)—proteins not known to be involved in cancer cell survival. OSBP and the ORPs constitute an evolutionarily conserved protein superfamily, members of which have been implicated in signal transduction, lipid transport and lipid metabolism. Cephalostatin 1 (1)¹, OSW-1 (2)², ritterazine B (3)³, schweinfurthin A (4)⁴, schweinfurthin B (5)⁴ and stellettin E⁵ (Fig. 1) are structurally diverse, naturally occurring small molecules that inhibit the growth of human cancer cell lines with half-maximal inhibitory concentrations (GI₅₀) in the nanomolar range^5–8. All five compounds induce a similar pattern of sensitivity against the National Cancer Institute 60 cancer cell lines (NCI-60). The NCI-DTP COMPARE algorithm can be used to assess the similarity of compound sensitivity to the NCI-60, expressed as Pearson correlation coefficients (r). Compounds with high COMPARE correlations (r > 0.6) tend to have related mechanisms⁹

Sesamin, piperine and silymarin promote cholesterol efflux and enhance ABCA1 expression.

Falcarindiol isolated from the roots and rhizomes of the traditional Chinese herbal drug Radix Notopterygii ("Qiang Huo") potently increases ABCA1 and promotes HDL cholesterol efflux.

SR-B1 is over-expressed in the majority of cancer tissues (HDL scavenger)

Targeting SREBP-1 and SREBP-2 lipid metabolism to treat cancer.

Betulin inhibits the biosynthesis of lipids and particularly SREBP-1 and SREBP-2.

Betulin (BE) is a pentacyclic triterpene and secondary metabolite of plants abundantly found in the outer bark of the birch tree Betulaceae sp. BE displays a broad spectrum of biological and pharmacological properties, among which the anticancer and chemo-preventive activity attract most of the attention.

Minerval® - 2-hydroxyoleic acid (2-OHOA/2OHOA) is an orally bioavailable synthetic derivative of oleic acid that crosses the Blood Brain Barrier and specifically activates sphingomyelin synthase 1 (SMS1), a key enzyme that catalyses the reversible conversion of PC, PE, PS and Cer into SM and DAG at the plasma membrane. Membrane lipid composition and organization is known to be significantly altered in cancer cells and it has been observed that these changes are enabling increased recruitement to the cell membrane of central proliferation signalling proteins, such as K-Ras. Abberant activity of Ras-associated proliferative signalling pathways (including MAP Kinases, pI3k/Akt/mTOR, PKC/Cyclin CDK or Notch) is exhibited in at least 1/3 of human cancers.

Selenium Tung Oil -

http://www.whnstore.com/Revici-Selenated-Tung-Oil-p/sup-tsel-1oz.htm?click=159

A very interesting reading material on Emanuel Revici's cancer research:

http://www.downloads.imune.net/medicalbooks/Dr%20Emmanual%20Revici%20medical%20system.pdf

This is the Selenium Tung Oil patent by Professor Revici -

http://library.whnlive.com/Revici/Patents/04564634_AntiNeoplastSe.pdf

There was a study done in Sweden called the The Swedish Apolipoprotein MOrtality RISk study (AMORIS) that contained information on more than 500 biomarkers collected from 397,443 healthy men and 414,630 healthy women from the greater Stockholm area during the period 1985–1996. Using this database, studies assessing risk of overall and site-specific cancers have been published, utilising a range of serum markers representing glucose and lipid metabolism, immune system, iron metabolism, liver metabolism, and bone metabolism. This is a summary of the Swedish study below:

http://ecancer.org/journal/9/full/555-metabolic-serum-biomarkers-for-the-prediction-of-cancer-a-follow-up-of-the-studies-conducted-in-the-swedish-amoris-study.php

The strongest relationship and connection to carcinogenesis was linked to serum gamma-glutamyltransferase, or transpeptidase, which was the old name of the enzyme (GGT). The study has investigated GGT serum levels in relation to cancer risk in 545,460 persons and found evidence of associations between elevated GGT and risk of developing different cancers. The strength of this association varied by levels of glucose which may suggest that hyperglycaemia can result in oxidative stress which in turn initiate damaging pathways of carcinogenesis.

Recent studies have made the connection between elevated GGT serum levels and insulin resistance.

Laboratory tests for insulin resistance most likely to be ordered include:

• Glucose. The goal of glucose testing is to determine whether a patient has an impaired response to glucose.
• HbA1c. This test is also called hemoglobin A1c, HbA1c, or a glycohemoglobin test and reflects average blood glucose levels over the past 3 months by measuring the percentage of hemoglobin that have been glycated, or bound with glucose, in the bloodstream.
• Lipid profile. This measures the HDL, LDL, triglycerides, and total cholesterol. If the triglycerides are significantly elevated, a DLDL (direct measurement of the LDL) may need to be done.
• One of the most common ways of detecting insulin resistance is by using the homeostatic model assessment (HOMA). It involves measuring glucose and insulin levels and then using a calculation to estimate function of the beta cells in the pancreas that produce insulin and insulin sensitivity.

Other laboratory tests that may be ordered to help evaluate insulin resistance and provide additional information include:

• Insulin. The fasting insulin test is variable, but insulin levels will usually be elevated in those with significant insulin resistance.
• hs-CRP. This is a measure of low levels of inflammation that may be done as part of an evaluation of cardiac risk. It may be increased with insulin resistance.

Insulin Resistance reversal is a KEY target in healthy recovery from cancer.

An excellent article from Dr. Lam again on how to reverse Insulin Resistance naturally. Pay particular attention to the DIET and SUPPLEMENTS suggested :

https://www.drlam.com/blog/reverse-insulin-resistance-naturally/295/

Chromium Polynicotinate & Vanadyl Sulfate - have been proven to treat insulin resistance and reverse it successfully.

Coconut oil, Momordica charantia (Bitter melon), Camellia sinensis (Green tea) and Cinnamon cassia (Chinese cinnammon) - have been successfully used to treat insulin resistance in phytotherapy.

Two protein hormones - adiponectin and leptin were also shown to completely reverse insulin resistance in mice.

Adiponectin is involved in regulating glucose levels as well as fatty acid breakdown. Berberine, an herbal folk medicine, has been shown to increase adiponectin expression which partly explains its beneficial effects on metabolic disturbances. Mice fed the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown increased plasma adiponectin. Curcumim, capsaicin, gingerol and catechins have also been found to increase adiponectin expression.

L-Arginine - has been clinically tested and confirmed to improve insulin resistance and also levels of adiponectin and leptin. You can refer to the below article for more information.

https://www.ncbi.nlm.nih.gov/pubmed/25335675

This article shows the link between insulin resistance and cholesterol metabolism - http://www.jlr.org/content/45/3/507.full.pdf

The 2017 Nobel Prize in Physiology and Medicine was awarded jointly to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for their discoveries of molecular mechanisms of controlling the circadian rhythm.

The circadian clock is our internal biological clock which is aligned with the planetary day and night cycle in a 24-hour period. But it is much more than that, this complex synchronicity mechanism is pervasive for the human organism and plays an important part in critical processes at a cellular level.

Disruptions in the circadian rhythm have been implicated in a number of diseases, including cancer for a long time. But only in recent years have scientists managed to shed more light on the actual molecular mechanism for the proper functioning and self-calibration of the biological circadian rhythm in the human body.

You can refer for the following article for some useful information on how one can target the circadian rhythm for cancer treatment: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-017-0349-7

Interestingly, the article above states that 1) the outcome of the tumorigenesis disease correlates with the level of improvement of circadian rhythmicity and 2) cancer prognosis and survival has been associated with the level of circadian disruption in patient tumor tissues.

Most of the clock genes play important roles in cell cycle regulation, DNA repair, immune system and metabolism and are involved in oncogenic pathways such as the RAS/MAPK.

The proliferation rate of cancer cells can be slowed down by more than 60% after intra-tumoral injections of dexamethasone by restoring carcadian clock gene expression.

Dexamethasone (DEX), Forskolin (FSK), and serum shock or heat shock activate the circadian clock in cancer cells, which regulates circadian expression of cell cycle genes, which results in slower tumor growth.

Seliciclib is a CDK inhibitor and also regulates circadian rhythm gene expression and successfully suppresses the proliferation of tumor cells.

Sphingolipids are commonly believed to protect the cell surface against harmful environmental factors by forming a mechanically stable and chemically resistant outer leaflet of the plasma membrane lipid bilayer. Certain complex glycosphingolipids were found to be involved in specific functions, such as cell recognition and signalling. Cell recognition depends mainly on the physical properties of the sphingolipids, whereas signaling involves specific interactions of the glycan structures of glycosphingolipids with similar lipids present on neighboring cells or with proteins.

Recently, simple sphingolipid metabolites, such as ceramide and sphingosine-1-phosphate, have been shown to be important mediators in the signaling cascades involved in apoptosis, proliferation, stress responses, necrosis, inflammation, autophagy, senescene, and differentiation. Ceramide-based lipids self-aggregate in cell membranes and form separate phases less fluid than the bulk phospholipids.

Sphingolipids are synthesized in a pathway that begins in the Endoplasmic Reticulum and is completed in the Golgi apparatus, but these lipids are enriched in the plasma membrane and in endosomes, where they perform many of their functions. Transport occurs via vesicles and monomeric transport in the cytosol. Sphingolipids are virtually absent from mitochondria and the Endoplasmic Reticulum, but constitute a 20-35 molar fraction of plasma membrane lipids.

Interestingly, naturally occurring 2-hydroxylated fatty acids exist. For instance, C22 to C26 saturated and monounsaturated 2-hydroxy fatty acids have been found as major lipid components of the cell wall in three marine chlorophytes , and detritus from the sea-grass Zostera muelleri is a source of 2-hydroxy acids (0.6 μg/g) that range from C₁₈ to C₂₈, including different mono- and polyunsaturated derivatives. Seed oils from Thymus vulgaris are enriched in 2-hydroxylinolenic acid (13%), while the seed oil of Salvia nilotica contains 0.6% 2-hydroxyoleic, 4.2% 2-hydroxylinoleic and 5.4% 2-hydroxylinolenic acids. Moreover, hydroxylated DHA derivatives may also be found among the aforementioned resolvins. During the last few years, a number of 2-hydroxylated fatty acid derivatives other than 2OHOA have been rationally designed for the treatment of cancer, inflammation, AD, obesity, diabetes, spinal cord injury, etc.… Indeed, the data available indicate that the mechanism of action of these compounds is related to their capacity to modulate the lipid structure of the membrane. In this context, 2OHOA has proved effective in reducing blood pressure in hypertensive rats through a mechanism that involves the modulation of membrane lipid composition, and of the membrane biophysical properties. Also, 2OHOA is currently being studied in phase I/IIa clinical trials for the treatment of solid tumors (code NCT01792310) and it is under pre-clinical development for the treatment of spinal cord injury.

As illustrated schematically in the figure above, platelet-derived growth factor (PDGF) induces sphingomyelin hydrolysis to ceramide (by sphingomyelinase), which is further metabolized (by ceramidase and sphingosine kinase) to sphingosine and sphingosine 1-phosphate. In contrast, tumor necrosis factor-α (TNF-α) usually activates only sphingomyelinase, which results in ceramide accumulation. These differences have profound effects on the behavior of the cells because sphingosine 1-phosphate is a potent mitogen and an inhibitor of apoptosis (Cuvillier et al. 1998, Olivera and Spiegel 1993), whereas sphingosine and ceramide inhibit growth and/or induce apoptosis (Hannun 1994, Jayadev et al. 1995, Sweeney et al. 1998).

https://academic.oup.com/jn/article/129/7/1239/4722573

"Apoptotic Sphingolipid Ceramide in Cancer Therapy"

Acid Ceramidase Inhibitors ???

Ceramidase

http://www.sciencedirect.com/science/article/pii/S0925443916300941

Citric Acid inhibits bacterial ceramidase -

https://www.nature.com/articles/ja201091

Poly-drug cancer therapy based on Ceramides

https://pdfs.semanticscholar.org/ed3c/b8fc89432e2f47a80bf7d5f8fe1243a39fb5.pdf

https://www.nature.com/articles/onc2011167

http://www.lipidhome.co.uk/lipids/sphingo.html

Daily intake of 100 ml of tart cherry juice in 2 divided doses (noon and one hour before going to bed) of roughly 50ml. This will provide melatonin for the body to heal and perform necessary repairs at night and also will neutralize the additional uric acid that comes from metabolizing ammonia. Pick a brand that does not contain a high amount of sugar - the least sugar, the better. Melatonin has a very important regulatory role for the fluidity of the cell membranes.

One of the ways that the tumors escape immune surveillance and host rejection is by a process called immune tolerance. Tumors escape the immune system due to an enzyme called indoleamine 2,3-dioxygense (IDO) which is highly up-regulated in a variety of cancers, and at the expense of melatonin synthesis. Taking methanol extract of the Japanese ginger flower buds would inhibit the IDO enzyme and will not allow the tumor to remain undetected by the host's immune system.

St. John's Wort is a medicinal plant that also suppresses the Kynurenine pathway by inhibiting tryptophan-2,3-dioxygenase (TDO). It has been shown that tryptophan 2,3-dioxygenase is expressed in a significant number of human tumors. Both IDO and TDO suppress T-lymphocyte function and thus weaken the immune system.

Yes, retinoids, including the listed above acne drugs are in my opinion a critical component of a successful recovery from the metabolic life threatening disease. They are helpful with the induction of differentiation of the cells (making them less cancerous and more normal cells) and they diminish the expression of CD133 which basically means that they fight the cancer stem cells by transforming their membrane structure and receptors and making them function normally again. CD133 is a cluster of differentiation that is often co-localized with cells with glucagon receptors and making the membranes of cells more rigid. It is expressed in almost all types of cancer and is a common denominator of cancer stem cells.

Forskolin activates the enzyme adenylyl cyclase and increases intracellular levels of cAMP. cAMP is an important second messenger necessary for the proper biological response of cells to hormones and other extracellular signals. It is required for cell communication in the hypothalamus/pituitary gland axis and for the feedback control of hormones via induction of corticotropin-releasing factor gene transcription. Forskolin also works with the circadian genes and re-sets the biological clock at a cellular level, which scientists have established has a great influence on cancer cells. Forskolin is an inhibitor of neutral endopeptidase (NEP) or CD10 and people with CD10+ positive cancers may find benefit from supplementing with Forskolin.

The efficacy of citrate therapy has been tested in various cancer models. Citrate administration inhibited awide arrray of various cancer cells and provided additional benefit accrued in combination with cisplatin treatment administration. Citric acid is a potent inhibitor of cancer cells' glucolysis. Further studies indicated that citrate induced tumor cell differentiation. Additionally, citrate treated tumor samples showed significantly higher infiltrating T-cells. Dr. Alberto Halabe Bucay is the pioneer pediatric oncologist who has proven the benefit of oral citric acid supplementation in the treatment of multiple types of cancer and significant increase in survival of a number of patients. The administered doses were between 7 -30 grams of citrci acid/day divided in 3 or 4 doses.

http://www.avemar.com/

It is already tested and proven in clinical trials that the eggplant vegetable is rich in Solasodine rhamnosyl glycosides (SRGs) which induce apoptosis in a wide variety of cancer cells and are more effective than many well-established anticancer agents. The main research on eggplant and its cytotoxic natural compounds has been done by Prof. Dr. Bill Elliot Cham.

Solasodine is also a potent agent to treat fungal infections including resistant Candida Albicans.a a

Scientific evidence has confirmed that capsaicin from cayenne peppers induces apoptosis in a number of different cancer cell lines through the activation and expression of TP53. Capsaicin has been shown to induce apoptosis in many different types of cancer cell lines including pancreatic, colonic, prostatic, liver, esophagieal, bladder, skin, leukemia, lung, and endothelial cells, while leaving normal cells unharmed. A recent review noted that capsaicin appears to induce apoptosis in over 40 distinct cancer cell lines.

One of the most important and successful protocols for treating cancer in my opinion is the Budwig protocol. I recommend using organic cold-pressed flaxseed oil and quark yogurt. I would caution you about grinding and adding the flaxseeds because the mixture's consistency would be very difficult to swallow, especially in the case of a late stage cancer patient. In my opinion, the healing effect is absolutely adequate when you only use the oil and quark mixed together really well. But here is the original preparation of the recipe from Johanna Budwig if you want to follow it exactly:

https://www.youtube.com/watch?v=7nMCXHpz_vI

The healing effects here are due to the correction of the composition of the cell membranes and should be noticed within 2-3 months, and on CT scan within 6 months.

One would need to take 150gr of quark with 4 tablespoons of organic cold-pressed flaxseed oil every day preferably in the morning.

In my opinion the omega-3 and omega-9 oleic acid in combination with the sulphur proteins from the quark yogurt pack a powerful punch against cancer cells and turn them back into normal cells by correcting the composition of the cell membrane.

For more information: https://www.budwigcenter.com/

Geraniol has been proven to work against multiple fungal strains including Candida Albicans, and many others including cancer stem cells with excellent results.

It should be employed by cancer patients as a strategy to eradicate any fungus in the human body.

The pharmacological activities of geraniol are: cardio-protective, anti-oxidant, anti-inflammatory, anti-tumor, antibacterial, and anti-fungal.

To date, experimental evidence supports the therapeutic or preventive effects of geraniol on different types of cancer, such as breast, lung, colon, prostate, kidney, skin, pancreatic, and hepatic cancer, and has revealed the mechanistic basis for its pharmacological actions. In addition, geraniol sensitizes tumor cells to commonly used chemotherapy agents.

A number of studies give the evidence that oleuropein, the active ingredient in olive leaf extract, is rather effective in fighting overgrowth of fungi. By improving your immunity against such unhealthy invaders as Candida, olive leaf extract decreases blood sugar, thus helping avoid yeast infections to begin with. Another study, which involved a dozen miscellaneous plant extracts, found that olive leaf offered more protection from mycotoxigenic fungi and pathogenic fungi, than any other compound tested.

Important for its effect on CD44 expression in cancer cells (stem cells).

Effective for the targeting of mucin expression in cancer.