Primer for Chiropractors A Primer for Chiropractors Andrew S. Bonci, BA, DC Andrew S. Bonci, BA, DC Mission, Kansas Mission, Kansas www.drbonci.com www.drbonci.com
special interest or special interest or lobbying groups nor do I receive lobbying groups nor do I receive stipends, consulting fees, stipends, consulting fees, gratuities or honoraria from any gratuities or honoraria from any pharmaceutical or nutritional pharmaceutical or nutritional companies. companies. I am I am NOT NOT a fan of Big Pharma a fan of Big Pharma or sell-out government officials or sell-out government officials and this may show. and this may show. Disclosures Disclosures
del cammin di nostra vita mi ritrovai per una selva oscura mi ritrovai per una selva oscura ché la diritta via era smarrita. ché la diritta via era smarrita. ~ Dante Alighieri ~
the journey of my life I found myself lost in a dark forest, I found myself lost in a dark forest, Having wandered off the main path. Having wandered off the main path. It is hard for me to express in words It is hard for me to express in words How savage, rough, and stern this forest was to me. How savage, rough, and stern this forest was to me. The very thought of it renews my fear. The very thought of it renews my fear. It was so bitter that death could not be worse; It was so bitter that death could not be worse; But in order to show you the good that I eventually But in order to show you the good that I eventually found, I must first tell you of the other things I saw. found, I must first tell you of the other things I saw. I cannot remember how I entered the forest, I cannot remember how I entered the forest, My thoughts were full of other things My thoughts were full of other things When I wandered off the path. When I wandered off the path. ~ Dante Alighieri ~
Genetic Terms Genetic Terms Look at Nutrition from the Look at Nutrition from the Perspective of Pancreatic Perspective of Pancreatic Cancer Cancer Examine Nutrient Control Examine Nutrient Control of Cell Cycle and Signal of Cell Cycle and Signal Processing Processing Explore Nutrients as Explore Nutrients as Chemoprotective and Chemoprotective and Chemotherapeutic Agents Chemotherapeutic Agents Hazard an Approach to a Hazard an Approach to a Healing Poetry Healing Poetry “Sanapoesis” “Sanapoesis”
en Términos Genéticos en Términos Genéticos Mirar a la Nutrición desde la Mirar a la Nutrición desde la Perspectiva de Cáncer Perspectiva de Cáncer Pancreático Pancreático Examinar el Control Examinar el Control Nutricional del Ciclo Celular Nutricional del Ciclo Celular y Procesamiento de Señales y Procesamiento de Señales Explorar Nutrientes como Explorar Nutrientes como Agentes Quimioterapéuticos Agentes Quimioterapéuticos y Quimioprotectores y Quimioprotectores Aventurar una Aventurar una Aproximación a una Poesía Aproximación a una Poesía Sanadora o “Sanapoesis" Sanadora o “Sanapoesis"
Genetikaj Terminoj Genetikaj Terminoj Rigardi Nutradon de la Rigardi Nutradon de la Perspektivo de Kancero Perspektivo de Kancero Pankreata Pankreata Ekzameni Nutran Ekzameni Nutran Kontrolon de Ĉela Ciklo Kontrolon de Ĉela Ciklo kaj Signala Procesorado kaj Signala Procesorado Esplori Nutraĵojn kiel Esplori Nutraĵojn kiel Kemiprotektaj kaj Kemiprotektaj kaj Kemiterapiaj Agentoj Kemiterapiaj Agentoj Riski Alproksimiĝo al Riski Alproksimiĝo al Resaniga Poezio aŭ Resaniga Poezio aŭ "Sanapoesis" "Sanapoesis"
Diagnosis. Diagnosis. Chiropractors don't Chiropractors don't Diagnose or Treat Medical Diagnose or Treat Medical Conditions. Conditions. How is “this” Chiropractic? How is “this” Chiropractic? Objections Objections
selfe; every man is No man is an Iland, intire of it selfe; every man is a peece of the Continent, a part of the maine; if a a peece of the Continent, a part of the maine; if a Clod bee washed away by the Sea, Europe is the Clod bee washed away by the Sea, Europe is the lesse, as well as if a Promontorie were, as well as lesse, as well as if a Promontorie were, as well as if a Mannor of thy friends or of thine owne were; if a Mannor of thy friends or of thine owne were; any mans death diminishes me, because I am any mans death diminishes me, because I am involved in Mankinde; And therefore never send to involved in Mankinde; And therefore never send to know for whom the bell tolls; It tolls for thee. know for whom the bell tolls; It tolls for thee.
itself. The Soul always knows what to do to heal itself. The challenge is to The challenge is to Silence the Mind. Silence the Mind. Carolyn Myss Photo by Dr. Marcos Lerma
the term prōsa ōrātio from the term prōsa ōrātio http://www.etymonline.com/index.php?term=prose Prosaic … commonplace or dull; Prosaic … commonplace or dull; matter-of-fact or unimaginative: matter-of-fact or unimaginative: a prosaic mind. a prosaic mind. http://dictionary.reference.com/browse/prosaic Prose Prose
broad meaning of a "making" or “creating”, seen also in such terms as "hemopoiesis" ... … as opposed to the prosaic ostensible meaning. http://en.wikipedia.org/wiki/Poetry Poetry Poetry
our present culture There is a systematic failure in our present culture to see meaning on multiple, interweaving levels. to see meaning on multiple, interweaving levels. This has brought us to a literal, uninspired This has brought us to a literal, uninspired and disastrous interpretation of life, and disastrous interpretation of life, health and disease. health and disease. King Philip the “Fair” of France and Pope Clement V accused the Templars of atheism, sodomy, blasphemy, and worse. Templars were tortured into forced confessions before being executed in large numbers. Scholars have debated whether any charges were true, but it is believed that they were innocent of the accusations and the process against them was solely for gaining access to their wealth and to ensure they could not become a political threat.
is as defined in a strictly traditional sense. • A tradition is a ritual, belief or object passed down within a society, still maintained in the present, with origins in the past. Thomas A. Green (1997). Folklore: an encyclopedia of beliefs, customs, tales, music, and art. ABC-CLIO. pp. 800–. ISBN 978-0-87436-986- 1. Latin stem of “trāditiō” means both “tradition” and “treason” I would like to open myself up to new ways to conceptualize how cells interpret the meaning of macronutrients and micronutrients. What v. How to Think About Nutrition
fuel that powers the machinery of the body Food as fuel that powers the machinery of the body Vitamins and minerals as co-enzymes and Vitamins and minerals as co-enzymes and metabolic co-factors in energy production metabolic co-factors in energy production Krebs Cycle Krebs Cycle
and still prevailing world view, nutrients are measured quantities of raw materials used as building blocks that are supplied to repair hardware and renew energy.
environmental signals. signals. Seasonality of foods tells Seasonality of foods tells the inside what's going on the inside what's going on outside. outside. Food availability may mark Food availability may mark circannual rhythms on a circannual rhythms on a cellular level. cellular level.
1944 was a famine that took place in the German-occupied part of the Netherlands. A German blockade cut off food and fuel shipments from farm areas to punish the reluctance of the Dutch to aid the Nazi war effort. Some 4.5 million people were affected and survived because of soup kitchens. Henri A. van der Zee, The Hunger Winter: Occupied Holland 1944-1945 (1998) pp. 304-305
exposed to the famine were more susceptible to diabetes, obesity, cardiovascular disease, microalbuminuria and other health problems. Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16757-8.
who were pregnant during the famine were smaller, as expected. However, surprisingly, when these children grew up and had children those children were also smaller than average. Epigenetics. 2009 Nov 16;4(8):526-31.
cancer or heart disease, we already know how to beat hunger: food.” we already know how to beat hunger: food.” Mario Batali Perhaps one can beat Perhaps one can beat cancer and heart disease cancer and heart disease with food as well. with food as well.
than fuel to power the metabolic engine. Nutrients are more than fodder to stoke the cellular furnace. Food is information as well as fuel. Nutrients are cellular or environmental signals.
nutrients have the ability to interact and modulate molecular mechanisms underlying an organism’s physiological functions has prompted a revolution in the field of nutrition. FASEB J. 2005 Oct;19(12):1602-16. Let Food be you Medicine, Let Food be you Medicine, and Medicine be your Food. and Medicine be your Food.
of an individual coordinates their response to diet, and thus considers underlying genetic polymorphisms. Curr Opin Lipidol. 2004 Apr;15(2):101-8. • In other words, nutrigenetics embodies the science of identifying and characterizing gene variants associated with differential responses to nutrients, and relating this variation to disease states. Annu Rev Genomics Hum Genet. 2004;5:71-118.
clearly different phenotypes exist in the same population of a species. http://en.wikipedia.org/wiki/Polymorphism_(biology) A polymorphism is a common change in the genetic code in DNA. http://www.cancer.gov/dictionary?cdrid=44805 Polymorphisms can have a harmful effect, a good effect, or no effect. Some polymorphisms have been shown to increase the risk of certain types of cancer. http://www.cancer.gov/dictionary?cdrid=44805
relates to biodiversity, genetic variation and adaptation. It functions to retain variety of form in a population living in a varied environment. • The most common example is sexual dimorphism, which occurs in many organisms. Other examples are human hemoglobin and blood types.
that the pants factory makes ONLY size medium trousers since this is the “average” size, it's been proven by research and mandated by law ... Now, let's imagine that a recommended daily Now, let's imagine that a recommended daily requirement of nutrients were established requirement of nutrients were established because it is an “average” requirement, because it is an “average” requirement, it's been proven and mandated by law ... it's been proven and mandated by law ... Now, let's imagine that a recommended dosage Now, let's imagine that a recommended dosage of chemotherapy/medicine were established of chemotherapy/medicine were established because it is an “average” requirement, because it is an “average” requirement, it's been proven and mandated by law ... it's been proven and mandated by law ...
polymorphism is an allelic variation. These allelic variations result in a variety or broad spectrum of protein/enzyme forms. The broad spectrum of protein or enzyme forms manifests itself in broad spectrum functionality. These polymorphs will have a need for full- spectrum nutritional support in order to encounter the “necessary nutrient blends.”
the broad co-factor/coenzyme complement to ensure optimal functionality to the individualized polymorphic expressions. Polymorphisms cannot accommodate to a diet of processed foods for the lack of the full-spectrum environmental/nutritional signals.
is, in effect, an evolutionary pressure that is The modern diet is, in effect, an evolutionary pressure that is forcing an extinction episode to which we are real-time witnesses. forcing an extinction episode to which we are real-time witnesses. The incompatibility between common polymorphic expressions The incompatibility between common polymorphic expressions and the modern mono-cultural, highly processed diet appears and the modern mono-cultural, highly processed diet appears to be a force in the causation of “disease” and, to be a force in the causation of “disease” and, consequently, our extinction … or evolution … ? consequently, our extinction … or evolution … ?
were a Survival Mechanism ... It would probably be because: • The modern, highly processed diet is devoid of the environmental signal required to supply the full spectrum, polymorphic needs of the cells. • Having unfulfilled needs, these cells would break their bonds with the their once vibrant cellular communities. • They would form a cellular “subculture” and live as “tissue” outcasts until they amassed sufficient numbers to command greater resources in order to ensure their survival. • When environmental-nutrient signal and metabolic resources become further strained, these renegade cells would aggressively try to satisfy their unmet needs by leaving their malignant communities.
Quorum sensing is a bacterial cell-cell communication process used to track increasing cell-population density and, in response to changes in cell number, coordinate gene coordinate gene expression and behavior on a community-wide expression and behavior on a community-wide scale scale. • Cells migrate toward/on target surfaces (organ-specific homing), show cell-cell and cell-matrix interactions (tumor cell- stromal cell crosstalk), remain subclinical until they can mount an effective attack (dormancy), form complex structures with channels for nutrient flow (vascularized lesions), and contain resistant cells which can cause disease recurrence (persistors). Clin Exp Metastasis. 2009;26(1):67-76.
essence of what It may in fact be, that the very essence of what individuals have to offer the world is through a close individuals have to offer the world is through a close understanding of their weaknesses and blind spots. understanding of their weaknesses and blind spots. ~David Whyte~
solid tumor mass in the head of the pancreas. CT scan confirms the findings of the abdominal ultrasound. We are fully aware of our odds and begin planning for the worst.
Serum tests become positive for the first time for elevated bilirubin and alkaline phosphatase. Exponential growth and doubling time press on our minds.
duct stent to remove obstruction. Endoscopic ultrasound examination confirms the mass, identifies local lymph node swelling and unusual liver appearance. She is diagnosed with Stage III Pancreatic Cancer. Referral is made to Jaswinder Singh, MD
into cancer care and management. Expressed a desire to use a standard chemotherapeutic agent approved for use in pancreatic cancer. Entertained a detailed discussion on nutritional co-management for cancers in general and pancreatic cancer in particular.
Gemzar® is a nucleoside metabolic inhibitor indicated for: • Ovarian cancer in combination with carboplatin • Breast cancer in combination with paclitaxel • Non-small cell lung cancer in combination with cisplatin • Pancreatic cancer as a single-agent http://pi.lilly.com/us/gemzar.pdf
Gemzar is for intravenous use only. • Pancreatic cancer: 1000 mg/m2 over 30 minutes once weekly for up to 7 weeks (or until toxicity necessitates reducing or holding a dose), followed by a week of rest from treatment. Subsequent cycles should consist of infusions once weekly for 3 consecutive weeks out of every 4 weeks • Dose Reductions or discontinuation may be needed based on toxicities. http://pi.lilly.com/us/gemzar.pdf
a known hypersensitivity to gemcitabine ----------------- WARNINGS AND PRECAUTIONS ---------------- • Hematology: Monitor for myelosuppression, which can be dose-limiting. • Pulmonary toxicity: Discontinue Gemzar immediately for severe pulmonary toxicity. http://pi.lilly.com/us/gemzar.pdf
killing cells undergoing DNA synthesis (S-phase) and also blocking the progression of cells through the G1/S-phase boundary. http://pi.lilly.com/us/gemzar.pdf
dosages Enhanced efficacy of gemcitabine by indole-3-carbinol in pancreatic cell lines: the role of human equilibrative nucleoside transporter 1. Anticancer Res. 2011 Oct;31(10):3171-80. Decrease the toxicity of GEMZAR Gender differences in gemcitabine (Gemzar) efficacy in cancer cells: effect of indole-3-carbinol. Anticancer Res. 2010 Dec;30(12):4907-13. Decrease the metastatic potential through its action of elastase(s), et. al. The dietary phytochemical indole-3-carbinol is a natural elastase enzymatic inhibitor that disrupts cyclin E protein processing. Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19750-5. Direct inhibition of elastase activity by indole-3-carbinol triggers a CD40-TRAF regulatory cascade that disrupts NF-kappaB transcriptional activity in human breast cancer cells. Cancer Res. 2010 Jun 15;70(12):4961-71. Convey endogenous antioxidant effects to the pancreas during chemo and radiation therapies. Induction of rat pancreatic glutathione S-transferase and quinone reductase activities by a mixture of glucosinolate breakdown derivatives found in Brussels sprouts. Food Chem Toxicol. 1998 May;36(5):365-73.
pancreatic cells. Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF. Cancer Res. 2010 May 1;70(9):3606-17. Sensitizes pancreatic cancer cells to gemcitabine. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. 2007 Apr 15;67(8):3853-61. Delay or eliminate development of resistance to gemcitabine. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. 2007 Apr 15;67(8):3853-61.
of myelosuppression. The relationship between treatment time of gemcitabine and development of hematologic toxicity in cancer patients. Biol Pharm Bull. 2011;34(11):1765-8.
have demonstrated that some natural products such as isoflavones, indole-3-carbinol (I3C), 3,3′-diindolylmethane (DIM), curcumin, (−)-epigallocatechin-3-gallate (EGCG), resveratrol, lycopene, etc, have inhibitory effects on human and animal cancers through targeting multiple cellular signaling pathways and thus these “natural agents” could be classified as multi-targeted agents. Cell Signal. 2009 Nov;21(11):1541-7.
signaling pathways including NF-κB, Akt, MAPK, Wnt, Notch, p53, AR, ER, etc, [...] natural products are known to activate cell death signals and induce apoptosis in pre-cancerous or cancer cells without affecting normal cells. Cell Signal. 2009 Nov;21(11):1541-7.
the bounties of nature could be useful either alone or in combination with conventional therapeutics for the prevention of tumor progression and/or treatment of human malignancies. Cell Signal. 2009 Nov;21(11):1541-7.
which describes how diet can impact gene expression and stability, should seek to provide gene expression and stability, should seek to provide recommendations on how to use diet to normalize recommendations on how to use diet to normalize gene expression for the purpose of reducing disease gene expression for the purpose of reducing disease and aiding recovery from disease, as well as to promote and aiding recovery from disease, as well as to promote continued good health for those who are disease free. continued good health for those who are disease free. J Nutrigenet Nutrigenomics. 2012;5(1):I-II. J Nutrigenet Nutrigenomics. 2012;5(1):I-II. Nutrigenomics Nutrigenomics
It would be cytotoxic to cancer cells. It would be cytotoxic to cancer cells. It would be non-toxic to normal cells. It would be non-toxic to normal cells. It would be inexpensive and abundantly It would be inexpensive and abundantly available. available. It would literally be like the grass that grows in It would literally be like the grass that grows in my yard. my yard. Cell Signal. 2009 Nov;21(11):1541-7.
name dandelion The common name dandelion is from the French dent-de-lion, is from the French dent-de-lion, meaning "lion's tooth". meaning "lion's tooth".
dandelion root extract in human pancreatic cancer cells BxPC-3 and PANC-1 pancreatic cells were sensitive to aqueous DRE. This extract induces selective apoptosis in a dose- and time-dependent manner. • Dandelion root extract caused the collapse of the mitochondrial membrane potential, leading to prodeath autophagy. • Normal human fibroblasts were resistant at similar doses. Pancreas. 2012 Oct;41(7):1039-47.
extract Dandelion Root Extract (DRE) is able to efficiently and selectively induce apoptosis and autophagy in human chronic myelomonocytic leukemia in a dose and time dependent manner, with no significant toxicity on non-cancerous peripheral blood mononuclear cells. PLoS One. 2012;7(2):e30604.
in drug-resistant human melanoma cells Various natural compounds have shown efficacy in killing different cancers, albeit not always specifically. In this study, we show that dandelion root extract (DRE) specifically and effectively induces apoptosis in human melanoma cells without inducing toxicity in noncancerous cells. • Therefore, treatment with this common, yet potent extract of natural compounds has proven novel in specifically inducing apoptosis in chemoresistant melanoma, without toxicity to healthy cells. Evid Based Complement Alternat Med. 2011;2011:129045.
still in its infancy. Intervention, to slow down, arrest or reverse the process of carcinogenesis, by the use of either natural or synthetic substances individually or in combination therapy has emerged as a promising and pragmatic medical approach to reduce cancer risk. This review asserts on the chemopreventive prospects of lupeol and reveals potential chemoprevention drug targets, central to which are the cell cycle regulatory pathway genes and tries to explain the mechanism operating behind its action. Cancer Lett. 2008 May 8;263(1):1-13.
Dandelion Tea Drink Dandelion Tea Take Dandelion Tinctures Take Dandelion Tinctures Bathe in Dandelions Bathe in Dandelions Have Dandelion Enemas Have Dandelion Enemas
modulators. Cannabinoids-endocannabinoids are anti- anti- inflammatory, anti-proliferative, anti-invasive, inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic anti-metastatic and pro-apoptotic in most cancers, in vitro and in vivo in animals. • They signal through p38, MAPK, JUN, PI3, AKT, ceramide, caspases, MMPs, VEGF, NF-κB, p8, CHOP, TRB3 and pro- apoptotic oncogenes (p53,p21 waf1/cip1) to induce cell cycle induce cell cycle arrest, autophagy, apoptosis and tumour inhibition arrest, autophagy, apoptosis and tumour inhibition. • They can also form bioactive, eicosanoid-like products that appear to be non-CBR ligands but have effects on NF-kB NF-kB transcription factors transcription factors. Prog Lipid Res. 2012 Oct 26. pii: S0163-7827(12)00053-7.
antioxidants and neuroprotectants Cannabinoids have been found to have antioxidant properties, unrelated to NMDA receptor antagonism. This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases. Inventors: Hampson; Aidan J. (Irvine, CA), Axelrod; Julius (Rockville, MD), Grimaldi; Maurizio (Bethesda, MD) Assignee: Assignee: The United States of America as represented by the Department of Health and Human Services The United States of America as represented by the Department of Health and Human Services (Washington, DC) (Washington, DC) Appl. No.: 09/674,028 Filed: February 2, 2001 PCT Filed: April 21, 1999 PCT No.: PCT/US99/08769 PCT Pub. No.: WO99/53917 PCT Pub. Date: October 28, 1999 http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO %2Fsrchnum.htm&r=1&f=G&l=50&s1=6630507.PN.&OS=PN/6630507&RS=PN/6630507
develop cancer. Quillin, Patrick (2011-11-15). Beating Cancer with Nutrition: Optimal Nutrition Can Improve Outcome inMedically-Treated Cancer Patients. (p. 53). BookMasters. Kindle Edition. What are Your Odds?
chance of living another 5 years, which are the same odds he or she had in 1971. Quillin, Patrick (2011-11-15). Beating Cancer with Nutrition: Optimal Nutrition Can Improve Outcome inMedically-Treated Cancer Patients. (p. 52). BookMasters. Kindle Edition. Chances of Survival is the Real Measure of Success
based on Claims for cancer drugs are generally based on tumor response rather than prolongation of life. tumor response rather than prolongation of life. Many tumors will initially shrink Many tumors will initially shrink when chemo and radiation are applied, when chemo and radiation are applied, yet tumors often develop drug-resistance yet tumors often develop drug-resistance and are then unaffected by therapy. and are then unaffected by therapy. Quillin, Patrick (2011-11-15). Beating Cancer with Nutrition: Optimal Nutrition Can Improve Outcome in Quillin, Patrick (2011-11-15). Beating Cancer with Nutrition: Optimal Nutrition Can Improve Outcome in Medically-Treated Cancer Patients. (p. 53). BookMasters. Kindle Edition. Medically-Treated Cancer Patients. (p. 53). BookMasters. Kindle Edition.
”We think we got it all.”-- that is when the war on cancer must become an invisible battle involving the patient’s well- nourished immune system. Quillin, Patrick (2011-11-15). Beating Cancer with Nutrition: Optimal Nutrition Can Improve Outcome inMedically-Treated Cancer Patients. (p. 60). BookMasters. Kindle Edition.
cause of cancer death in this country, and each year, ~30,000 Americans die of the disease. In this deadly disease, the mortality rate approximately equals the incidence rate. American Cancer Society. Cancer figures and facts, 2004. Atlanta: American Cancer Society; 2004.
to exhaustion is not necessarily rest. necessarily rest. The antidote to exhaustion is whole- The antidote to exhaustion is whole- heartedness. heartedness. ~ David Steindl-Rast ~ ~ David Steindl-Rast ~
One million cancer cells = head of a pin One billion cancer cells = a small grape 230 = 1,073,741,824 = 1 billion cells 2-6 weeks Cancer cells reproduce every 2-6 weeks. 2-6 weeks 2-6 weeks 2-6 weeks
process that is activated Carcinogenesis is a multistep process that is activated by altered expression of transcriptional factors and proteins by altered expression of transcriptional factors and proteins involved in proliferation, cell cycle regulation, differentiation, involved in proliferation, cell cycle regulation, differentiation, apoptosis, angiogenesis, invasion and metastasis. apoptosis, angiogenesis, invasion and metastasis. Cancer Lett. 2008 Oct 8;269(2):352-62.
apoptosis Deregulated cell cycle progression and apoptosis together with increased angiogenic potential, together with increased angiogenic potential, invasion and metastasis have been described invasion and metastasis have been described as hallmarks of cancer. as hallmarks of cancer. Cancer Lett. 2008 Oct 8;269(2):352-62.
CDK Supervised by Tumor Suppressor Proteins Coordinated by Nutritional Signals The purpose of cell cycle processes is genetic transcription and expression.
mechanisms that ensure the fidelity of cell division in eukaryotic cells. Science. 1994 Dec 16;266(5192):1821-8. These checkpoints verify whether the processes at each phase of the cell cycle have been accurately completed before progression into the next phase. • G1/S Checkpoint • G2 Checkpoint • Metaphase Checkpoint
that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (Cdk) enzymes. Oncogene. 2003 Aug 11;22(33):5208-19. G1/S Cyclins rise in late G1 and fall in early S phase. The Cdk- G1/S cyclin complex begins to induce the initial processes of DNA replication. PLoS One. 2012;7(1):e28568.
signals (i.e., DNA damage) regulate the formation of cyclin-CDK complexes via cyclin- dependent kinase inhibitors (CKI), which include the cip/waf family (p21, p27, p57). Annu. Rev. Nutr. 2004. 24:433–53 The cip/waf family interacts with multiple cyclin-CDK complexes and the INK4 family (p15, p16, p18, p19), which specifically inhibits cyclin D-CDK complexes. Annu. Rev. Nutr. 2004. 24:433–53
is coded for by a tumor suppressor gene is produced in response to cellular stress: • DNA damage • Oxidative stress • Osmotic shock • RNA depletion • Deregulated oncogene expression http://en.wikipedia.org/wiki/Tumor_suppressor_protein_p53
and activates expression of several genes including microRNA, WAF1/CIP1 encoding for p21 and hundreds of other down-stream genes. • p21 (WAF1) binds to the G1-S/CDK (CDK2) and S/CDK complexes (molecules important for the G1/S transition in the cell cycle) inhibiting their activity. Leukemia. 2009 Jun;23(6):1159-63
Hunter-Gatherer beginning Cells have a Hunter-Gatherer beginning before they formed Communities of Cells. before they formed Communities of Cells. When the needs of the individual or community When the needs of the individual or community are not met, behaviors are changed are not met, behaviors are changed in order to meet the perceived or real needs. in order to meet the perceived or real needs. Essentially, they pick up and leave. Essentially, they pick up and leave.
in their unfractionated, whole and natural state. Nutrients‡ that Exert a Chemoprotective and/or Chemotherapeutic Effect Against Cancer by Influencing: • Cell Cycle Progression • Apoptosis • Metastasis • Angiogenesis
of natural products to the expansion of the chemotherapeutic arsenal is evidenced by the fact that 50% of all the anticancer drugs approved worldwide between 1940 and 2006 were either natural products or natural product derived. J Nat Prod. 2007 Mar;70(3):461-77.
a multitude of nutritional and The diet is comprised of a multitude of nutritional and chemical molecules each capable of regulating disparate chemical molecules each capable of regulating disparate biological processes, and thus cannot use an approach biological processes, and thus cannot use an approach Similar to the pharmaceutical industry, Similar to the pharmaceutical industry, i.e., the “one drug one target” paradigm. i.e., the “one drug one target” paradigm. Curr Opin Biotechnol. 2001 Oct;12(5):516-22.
analysis indicates that retinoic acid (RA) inhibition of MCF-7 cell growth occurs through induction of G1 arrest with a concomitant reduction in the proportion of cells in S and G2 + M phases. • E2F1 promoter activity was reduced by 60%. Exp Cell Res. 1997 Aug 1;234(2):293-9
known as death receptor 4) is a transmembrane receptor that mediates TRAIL-induced apoptosis in cancer cells. • ATRA accentuates TRAIL-induced apoptosis, reveal a novel mechanism by which retinoids modulate apoptosis, and suggest a novel strategy to augment the anti-cancer activity of TRAIL. Cancer Res. 2011 Aug 1;71(15):5245-54.
death of patients with liver cancer. • Type IV collagen is the main structure protein of basilar membrane which is a natural barrier for inhibiting the metastasis of liver cancer cells. All trans-retinoic acid (ATRA) to inhibits collagenase type IV in order to protect the type IV collagen and basilar membrane, to further suppress the metastasis of hepatocellular carcinomas. Hepatobiliary Pancreat Dis Int. 2004 Nov;3(4):588-90.
growth and has anticancer effects on transplantable tumor growth of human (esophageal squamous cancer cell) ESCC cell line EC9706 in nude mice. • These findings indicate that ATRA specifically down regulated VEGF and the components of VEGF signal transduction, which may be an important mechanism responsible for the neoangiogenesis inhibition of ESCC cells. Chin Med J (Engl). 2011 Sep;124(17):2708-14.
superoxide dismutase mRNA, protein, and activity levels increased in a time- dependent manner upon treatment with ATRA. • This study identifies SOD2 as a retinoid-responsive gene. • These results suggest that signaling events involving NF- kappaB and SOD2 may contribute to the effects of retinoids used in cancer therapy. Free Radic Biol Med. 2008 Apr 15;44(8):1610-6.
adenocarcinoma results in inhibition of growth, induction of cellular differentiation and decreased adhesion to certain components of the extracellular matrix, all features compatible with a "less malignant" phenotype. • In summary, these studies suggest that retinoids might be beneficial in the treatment of advanced pancreatic carcinoma patients based on their pleiotropic effects on tumor cell biology. Ann Oncol. 1999;10 Suppl 4:197-200.
pancreatic cancer cells Retinoids are potent growth inhibitory and differentiating agents in a variety of cancer cell types. Retinoids induce growth arrest in all pancreatic cancer cell lines studied, regardless of their p53 and differentiation status. • Retinoic acid markedly inhibited proliferation of two cell lines (Capan-2 and Hs766T) in a concentration and time-dependent manner. Mol Cancer. 2007 Dec 24;6:82.
growth inhibition in pancreatic cancer cells. Acyclic retinoid (ACR), a new synthetic retinoid, 9-cis-retinoic acid and gemcitabine preferentially inhibited the growth of human pancreatic cancer cells (Panc-1 and KP-2) in comparison to normal human pancreatic epithelial cells. • The combination of ACR plus gemcitabine synergistically inhibited the growth of Panc-1 cells. Cancer Lett. 2009 Jan 18;273(2):250-6.
β-carotene in U937 and HL-60 leukemia cells. When [leukemic] cells were treated with 20 microM of beta-carotene, total genomic DNA showed a fragmentation pattern. • Both the cell lines, on treatment with beta- carotene, showed a clear shift in G(1) phase of the cell cycle. J Biochem Mol Biol. 2007 Nov 30;40(6):1009-15 .
reduces the number of tumor-directed capillaries. Beta-carotene is able to inhibit proliferation, migration, and tube formation of endothelial cells. • Beta-carotene treatment downregulates the expression of matrix metalloproteinase (MMP)-2, MMP-9, prolyl hydroxylase, and lysyl oxidase gene expression and upregulates the expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Integr Cancer Ther. 2007 Sep;6(3):258-70.
against the law and until it turns your skin orange. Supplements: Take only supplements containing mixed carotenes to obtain a broad spectrum of carotene activity.
with decreased risk of prostate cancer. Lycopene increased the number of cells in the G(2)/M phase of the cell cycle and decreased S-phase cells while no shifts in cell cycle were detected in placebo-treated groups. • Lycopene, therefore, deserves further study as a potential chemopreventive/chemotherapeutic agent. J Med Food. 2004 Fall;7(3):284-9.
cycle progression in human cancer cell lines. [The] data shows a significant decrease in the number of viable cells in three cancer cells lines (HT- 29, T84 and MCF-7) after 48 h treatment with lycopene, and changes in the fraction of cells retained in different cell cycle phases. • Lycopene promoted also cell cycle arrest followed by decreased cell viability in majority of cell lines after 96 h, as compared to controls. Furthermore, an increase in apoptosis was observed in four cell lines (T-84, HT-29, MCF-7 and DU145) when cells were treated with lycopene. Cancer Cell Int. 2012 Aug 6;12(1):36.
cause of cancer death. We showed that lycopene inhibited SK-Hep-1 migration and invasion in a bell-shaped manner. Lycopene was much more effective than β- carotene in reducing cell invasion. • We conclude that lycopene has significant antimigration and anti-invasion activity. J Nutr. 2005 Sep;135(9):2119-23.
and growth, and is therefore a promising target for cancer therapy. The anti-angiogenic effects of lycopene in the present study were shown at a concentration that should be achievable by dietary means. • These results extend our knowledge of one of the putative anti- cancer actions of lycopene. Br J Nutr. 2012 Aug;108(3):431-9.
pancreatic cancer risk 462 histologically confirmed pancreatic cancer cases and 4721 population-based controls were compared to each other and against a self- adminstered dietary intake assessment. • Lycopene, provided mainly by tomatoes, was associated with a 31% reduction in pancreatic cancer risk. • The results of this study suggest that a diet rich in tomatoes and tomato-based products with high lycopene content may help reduce pancreatic cancer risk. J Nutr. 2005 Mar;135(3):592-7.
carotenoid pigment and phytochemical found in tomatoes and other red fruits and vegetables, such as red carrots, red bell peppers, watermelons, and papayas (but not strawberries or cherries). Although lycopene is chemically a carotene, it has no vitamin A activity. J Am Coll Nutr October 2000 vol. 19 no. 5 563-569
research that has produced a tomato that is perfect in every respect, except that you can't eat it. We should make every effort to make sure this disease, often referred to as 'progress', doesn't spread. Andy Rooney
G1-S checkpoint in ovarian cancer cells 1,25(OH)(2)D(3) suppressed activation of the external signal regulated kinase by epidermal growth factors. • Taken together, our studies demonstrate that 1,25(OH)(2)D(3) suppresses the response of human ovarian cancer cells to mitogenic growth factors and couple the suppression to the cell cycle arrest at G1-S checkpoint by the hormone. Mol Cell Endocrinol. 2011 May 16;338(1-2):58-67.
anti-tumor effects mainly through the induction of cancer cell apoptosis, cell cycle arrest, differentiation, angiogenesis and the inhibition of cell invasiveness by a number of mechanisms. • Calcitriol enhances the cytotoxic effects of gamma irradiation and certain antioxidants and naturally derived compounds. J Cancer. 2010 Jul 15;1:101-7.
the anti-tumor activities of multiple chemotherapeutics agents including DNA-damaging agents cisplatin, carboplatin and doxorubicin; antimetabolites 5-fluorouracil, cytarabine, hydroxyurea, cytarabine and gemcitabine; and microtubule-disturbing agents paclitaxel and docetaxel. J Cancer. 2010 Jul 15;1:101-7.
pancreatic cancer Vitamin D seems to have a protective effect against pancreatic cancer by participating in numerous proapoptotic, antiangiogenic, anti- inflammatory, prodifferentiating, and immunomodulating mechanisms. • Sun exposure has been associated with lower incidence of pancreatic cancer in ecological studies. • Increased vitamin D levels seem to protect against pancreatic cancer, but caution is needed as excessive dietary intake may have opposite results. J Nutr Metab. 2010;2010:721365.
Get a tan or go extinct. Take orally what your body Take orally what your body can make with full body can make with full body exposure at the MED*. exposure at the MED*. Oral recommendations is Oral recommendations is between 10,000IU/day to between 10,000IU/day to 25,000IU/day. 25,000IU/day. * Minimal Erythemal Dose
(Curcuma longa) is a rhizomatous herbaceous perennial plant of the ginger family, Zingiberaceae. perennial plant of the ginger family, Zingiberaceae. It is native to tropical South Asia. It is native to tropical South Asia. In medieval Europe, turmeric became known as In medieval Europe, turmeric became known as Indian saffron since it was widely used as an alternative Indian saffron since it was widely used as an alternative to the far more expensive saffron spice. to the far more expensive saffron spice. The etymology of the word "turmeric" comes from The etymology of the word "turmeric" comes from the Latin "terra merita", literally "deserving earth". the Latin "terra merita", literally "deserving earth". http://en.wikipedia.org/wiki/Turmeric http://en.wikipedia.org/wiki/Turmeric
and G(2)/M phase arrest in human osteosarcoma (HOS) cells. • The G(1)/S and G(2)/S phase arrest was accompanied by down-regulation of cyclin D1, cdc2 and cyclin B1, respectively. Anticancer Res. 2009 Dec;29(12):5039-44.
proposed for cancer chemoprevention since it induces apoptosis and inhibits the formation of breast cancer metastases. Curcumin impairs transcription of CXCL1 and -2. This mitogenic chemokine silencing leads to down regulation of several metastasis-promoting genes. • We therefore suggest that the decrease of CXCL1 and -2 mediated by Curcumin is involved in the inhibition of metastasis. Carcinogenesis. 2008 Apr;29(4):779-89.
and MMP-3 were inhibited by curcumin in a dose-dependent manner. • This study suggests that the suppression of MMP-1 and MMP-3 production by curcumin in CIA is mediated through the inhibition of PKCdelta and the JNK/c-Jun signaling pathway. J Pharmacol Sci. 2009 Sep;111(1):13-21.
closely associated with inflammation and cancer were found to be modulated by curcumin. These enzymes include COX-2, inducible nitric oxide synthase (iNOS), 5-LOX, and phospholipases A2 (PLA2). • Curcumin exhibits an inhibitory effect on all of these proinflammatory enzymes. Curr Drug Targets. 2011 Mar 1;12(3):332-47.
production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also suppressed osteoclastogenesis. Mol Nutr Food Res. 2012 Mar;56(3):454-65.
animals and human volunteers The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. Concomitant administration of piperine increased bioavailability of curcumin by 2000%. • The study shows that piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects. Planta Med. 1998 May;64(4):353-6.
with turmeric until your breath and your sweat carries its odor. Mix it with your formula and push it in through your GJ-Tube. Take it as tablets, capsules or tinctures with piperine.
of the genus Silybum Adans., a flowering plant of the daisy family (Asteraceae). The plant is native to the Mediterranean regions of Europe, North Africa and the Middle East. http://en.wikipedia.org/wiki/Milk_thistle
in human prostate cancer PC3 cells Molecular studies showed that G1 arrest was associated with a decrease in cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase (CDK)4, CDK6 and CDK2 protein levels, and CDK2 and CDK4 kinase activity, together with an increase in CDK inhibitors (CDKIs) Kip1/p27 and Cip1/p21. Oncogene. 2006 Feb 16;25(7):1053-69.
silibinin possesses a strong antineoplastic potential against many cancers. Silibinin treatment inhibited cell growth and targeted cell-cycle progressing causing a prominent G(1) arrest. • In mechanistic studies, silibinin modulated the protein levels of cyclin-dependent kinases (4, 6, and 2), cyclins (D1, D3, and E), CDKIs (p18/INK4C, p21/Cip1, and p27/Kip1). Mol Carcinog. 2010 Mar;49(3):247-58.
chemopreventive agent in various epithelial cancer models, has been reported to inhibit cancer cell growth in cervical cancer. Silibinin treatment of HeLa cells resulted in a G2 arrest and induced a decrease in cyclin- dependent kinases involved in both G1 and G2 progression. • In addition, a strong rationale for future studies evaluating preventive and/or intervention strategies for silibinin in cervical cancer. Cell Biochem Funct. 2012 Apr;30(3):243-8.
that silibinin induces p21/Cip1 and p27/Kip1 and G1 arrest in different prostate cancer cells irrespective of p53 status. • Our results for the first time identify a central role of p21 and p27 induction and their regulatory mechanism in silibinin- mediated cell cycle arrest. Mol Cancer Ther. 2007 Oct;6(10):2696-707.
treatment inhibited cell growth and induced cell death. Silibinin also decreased cyclin-dependent kinase 8 and cyclin C expression. • Together, these findings suggest that silibinin inhibits the growth of CRC tumors and, therefore, could be an effective agent against CRC. Neoplasia. 2010 May;12(5):415-24.
in cancer therapy. The treatment of the leukemia (K562) cells with silymarin (a standardized mixture of flavonolignans) resulted in a significant inhibition of cell growth and telomerase activity. • These results suggest a novel mechanism in the anticancer activity of silymarin in human leukemia K562 cells and may provide a basis for future development of anti-telomerase therapies. Planta Med. 2012 Jun;78(9):899-902.
in prostate cancer (PCA) growth and metastasis is well established. The oral feeding of these flavonolignans effectively inhibited the growth of advanced human PCA (DU145) xenografts. • These studies elucidated the comparative anti-angiogenic efficacy of pure flavonolignans from Milk Thistle and suggest their usefulness in PCA angioprevention. PLoS One. 2012;7(4):e34630.
is a leading cause of death from skin diseases, and is often associated with activation of Wnt/β-catenin signaling pathway. We found that treatment of human melanoma cell lines with silymarin resulted in inhibition of cell migration. • These results indicate for the first time that silymarin inhibits melanoma cell migration by targeting β-catenin signaling pathway. PLoS One. 2011;6(7):e23000.
Take Milk Thistle in all 4 forms: Liquid Extract Liquid Extract Drink it as Tea Drink it as Tea Powdered Capsule Powdered Capsule Hard Capletes Hard Capletes Titrate to nausea, then reduce below nausea. Titrate to nausea, then reduce below nausea.
of several known isoflavones. Isoflavones, such as genistein and daidzein, are found in a number of plants including lupin, fava beans, soybeans and coffee. J Agric Food Chem 41 (11): 1961–1967. J Altern Complement Med 3 (1): 7–12. J Agric Food Chem 58 (5): 3002–3007.
inhibited in a dose-dependent manner the growth of HGC-27 cells derived from human gastric cancer. [A]nalysis showed that genistein almost completely arrested the cell cycle progression at G2-M. • This effect was reversible when genistein was removed from the culture medium. Cancer Res. 1993 Mar 15;53(6):1328-31.
is a growing body of experimental evidence showing that the inhibition of human cancer cell growth by genistein is mediated via the modulation of genes that are related to the control of cell cycle and apoptosis. • Genistein, one of the major soy isoflavones is a promising agent for cancer chemoprevention and further suggest that it could be an adjunct to cancer therapy by virtue of its effects on reversing radioresistance and chemoresistance. Cancer Lett. 2008 Oct 8;269(2):226-42.
diet has been linked to decreased rates of metastatic cancer in a number of population-based studies. • At lower concentrations that are similar to those achieved through dietary consumption, genistein can inhibit the prometastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms. Cancer Metastasis Rev. 2010 Sep;29(3):465-82.
in vitro and in vivo Genistein pretreatment together with low concentration of Oxaliplatin (OxP) showed significant reduction in cell viability and colony formation concomitant with increased apoptosis (p < 0.01), which was highly synergistic. • From these results, we conclude that genistein sensitizes drug-resistant PC to OxP resulting in greater antitumor effects, and thus our data suggest that this approach could be useful in improving the treatment outcome for patients diagnosed with PC. Int J Cancer. 2011 Mar 1;128(5):1240-50.
a movie and Watch a movie and snack on non-GMO Edemame. snack on non-GMO Edemame. Put it in your children's lunch box. Put it in your children's lunch box. Invent a way to turn fava beans Invent a way to turn fava beans Into snack chips. Into snack chips.
derivative from A green tea extract is a herbal derivative from green tea leaves (Camellia sinensis). green tea leaves (Camellia sinensis). Containing antioxidant ingredients Containing antioxidant ingredients – – mainly green tea catechins (GTC) mainly green tea catechins (GTC) – – green tea and its derivatives. green tea and its derivatives. http://en.wikipedia.org/wiki/Green_tea_extract
tea and is a potent antioxidant that may have therapeutic applications in the treatment of many disorders (e.g. cancer). It is found in green tea but not black tea. http://en.wikipedia.org/wiki/Epigallocatechin_gallate
cancer line, SKOV-3 cells showed inhibition of cell viability and proliferation in a dose-dependent manner. • In SKOV-3 cells, EGCG inhibits cell proliferation via DNA synthesis reduction and induces apoptotic cell death via DNA damage, thus elucidating a novel, plausible mechanism of EGCG anti-tumorigenic property. Anticancer Res. 2010 Jul;30(7):2519-23.
to the treatment of lung cancer. • This study showed that epigallocatechin-3-gallate (EGCG), a natural polyphenol in green tea, is a potent inhibitor of MMP-2 expression. • EGCG effectively suppressed the invasion and migration of highly invasive CL1-5 lung cancer cells. J Agric Food Chem. 2011 Dec 28;59(24):13318-27.
major causes of mortality in bladder cancer patients. Mechanistically, EGCG inhibited [...] the expression of matrix metalloproteinase-9 (MMP-9), ultimately suppressing invasion and metastasis. • These findings suggest that EGCG is a potential therapeutic candidate against tumor invasion. Mol Med Report. 2012 Nov;6(5):1040-4.
decrease VEGF receptor phosphorylation and induces apoptosis in chronic lymphocytic leukemia B cells. Leukemia. 2005 Apr;19(4):513-23. [T]he inhibition of VEGF binding to its receptor may contribute to the antiangiogenic and cancer chemopreventive effects of EGCG. Cancer Res 66: 2500-2505, 2006.
reduced the protein expression and activity of COX-2 following interleukin-1h stimulation of human chondrocytes. • Most research findings strongly suggest that development of chemopreventive compounds, which can block COX-2 expression preferably without affecting COX-1, is a high priority for cancer research. Cancer Res 66: 2500-2505, 2006.
human pancreatic cancer. The effects of epigallocathechin gallate (EGCG) in pancreatic cancer cells were assessed with gemcitabine for the treatment and/or prevention of pancreatic cancer. • EGCG inhibited cell motility, migration and invasion • Gemcitabine synergized with EGCG to inhibit cell viability and induce apoptosis in pancreatic cancer cells. PLoS One. 2012;7(2):e31067.
Use Green Tea Tinctures Use Green Tea Tinctures Take Green Tea Supplements Take Green Tea Supplements Eat Green Tea Ice cream Eat Green Tea Ice cream Have Green Tea Enemas Have Green Tea Enemas Take Green Tea Baths Take Green Tea Baths
arrest in activated hepatic stellate cells Resveratrol (RSV) exerts anti-proliferative and pro-apoptotic actions in different cell lines. RSV induced an increase in the number of [hepatic cancer] cells in the S- and sub-G1 phases. • It is notable that these RSV actions are mediated at nanomolar levels, compatible with the concentrations of free RSV in biological fluids after ingestion of polyphenol-rich foods, suggesting a possible effect of these foods as an adjuvant treatment in chronic liver diseases. Mol Cell Biochem. 2008 Aug;315(1-2):1-7.
in vitro studies revealed multiple intracellular targets of resveratrol, which affect cell growth, inflammation, apoptosis, angiogenesis, and invasion and metastasis. • These include tumor suppressors p53 and Rb; cell cycle regulators, cyclins, CDKs, p21WAF1, p27KIP and INK and the checkpoint kinases; transcription factors NF-kappaB; angiogenic and metastatic factors, VEGF and matrix metalloprotease 2/9; cyclooxygenases for inflammation; and apoptotic and survival regulators. Arch Biochem Biophys. 2009 Jun 15;486(2):95-102 .
wound migration, invasion, and MMP-9 activity were significantly decreased in a dose-dependent manner in 4T1 (metastatic breast cancer) cells (P < 0.05). • The numbers of pulmonary nodules were significantly decreased in mice fed the resveratrol (P < 0.05). • The plasma MMP-9 activity was decreased in response to treatment with resveratrol in mice (P < 0.05). • We conclude that resveratrol inhibits cancer metastasis both in vitro and in vivo, and this inhibition is likely due to the decrease in MMP-9 activity caused by resveratrol. Nutr Res Pract. 2012 Aug;6(4):294-300.
Resveratrol directly bound to leukotriene A(4) hydrolase (LTA(4)H) in vitro and in cells and suppressed proliferation and growth of pancreatic cancer by inhibiting LTB(4) production and expression of the LTB(4) receptor 1 (BLT(1)). • Importantly, resveratrol inhibited tumor formation in a xenograft mouse model of human pancreatic cancer by inhibiting LTA(4)H activity. • Our findings identify LTA(4)H as a functionally important target for mediating the anticancer properties of resveratrol. Cancer Res. 2010 Dec 1;70(23):9755-64.
cancer cell Resveratrol inhibited the growth of pancreatic cancer cells in a dose- and time-dependent manner. • Compared with control group, the cells in the G0/G1 phase and the apoptosis rate were significantly increased. Pancreatology. 2011;11(6):601-9.
pancreatic cancer New agents that are safe and effective are highly needed. Resveratrol is one such agent which is safe and multitargeted; and has been linked with suppression of survival, proliferation, invasion and angiogenesis of cancer. • Resveratrol inhibited the proliferation of 4 different human PaCa cell lines, synergized the apoptotic effects of gemcitabine, inhibited the constitutive activation of NF-kappaB and expression of bcl-2, bcl-xL, COX-2, cyclin D1 MMP-9 and VEGF. Int J Cancer. 2010 Jul 15;127(2):257-68.
pancreatic cancer In an orthotopic model of human PaCa, we found that resveratrol significantly suppressed the growth of the tumor (p < 0.001) and this effect was further enhanced by gemcitabine (p < 0.001). • As compared to vehicle control, resveratrol also suppressed the NF-kappaB activation and expression of cyclin D1, COX-2, ICAM-1, MMP-9 and survivin. Overall our results demonstrate that resveratrol can potentiate the effects of gemcitabine through suppression of markers of proliferation, invasion, angiogenesis and metastasis. Int J Cancer. 2010 Jul 15;127(2):257-68.
cranberries, blueberries, blackberries, raspberries, goji berries, blackberries, raspberries, goji berries, frankenberries, matthiasberries, frankenberries, matthiasberries, manfrediberries ... manfrediberries ... Drink red wines, fresh juices Drink red wines, fresh juices Bathe in it, wash with it, use it as an enema. Bathe in it, wash with it, use it as an enema. Take Resveratrol Supplements Take Resveratrol Supplements Recommendations Recommendations
compound that occurs naturally in Brassica vegetables such as cabbage and broccoli, can induce a G1 cell-cycle arrest of human MCF-7 breast cancer cells that is accompanied by the selective inhibition of cyclin-dependent kinase 6 (Cdk6) expression and stimulation of p21(Waf1/Cip1) gene expression. J Nutr. 2003 Jul;133(7 Suppl):2448S-2455S.
of in vitro cell adhesion, migration, and invasion as well as in vivo lung metastasis. I3C also suppressed the 17beta-estradiol stimulated migration and invasion in estrogen- responsive MCF-7 cells. • I3C significantly caused a dose-dependent increase in BRCA1 expression. • Clinical application of I3C may contribute to the potential benefit for suppression of breast cancer invasion and metastasis. J Mol Med (Berl). 2000;78(3):155-65.
prostate cancer cells Indole-3-carbinol (I3C) induces a G1 growth arrest of human reproductive cancer cells. • We previously reported that in LNCaP prostate cancer cells, I3C down-regulated cyclin-dependent kinase (CDK) 2 activity. I3C increased the level of activated p53 nuclear protein that is competent to bind its DNA target site on the p21 promoter. Biochem Pharmacol. 2006 Dec 15;72(12):1714-23.
urine and your Eat, eat, eat them until your urine and your pooh smells like cabbage or broccoli. pooh smells like cabbage or broccoli. Take I3C and DIM supplements Take I3C and DIM supplements Use the pot liquor to bathe wounds and as an Use the pot liquor to bathe wounds and as an enema enema Make poultices to care for wounds it them Make poultices to care for wounds it them
of cellular growth can also be influenced by nutrients through their use as co- factors in enzymes required for DNA synthesis and the control of genomic structural integrity. • Recently some of these nutrient dependent enzymes have become targets in chemotherapeutic treatments to inhibit DNA synthesis in tumor cells. Annu. Rev. Nutr. 2004. 24:433–53
variety of tumor tissues iron chelation causes decreased levels of cyclin D1, D2, and D3, and hypophosphorylation of Rb resulting in G1/S arrest. Blood. 2001 Aug 1;98(3):842-50. Exp Cell Res. 1996 Nov 25;229(1):60-8. J Invest Dermatol. 2000 Nov;115(5):893-900.
has been shown to have antiproliferative effects both in vitro and in vivo on numerous types of tumors, including rat mammary adenocarcinoma, human hepatocellular carcinoma, human neuroblastomas, and human acute leukemias. Anticancer Res. 1999 Jan-Feb;19(1A):445-50. Crit Rev Oncol Hematol. 2002 Jun;42(3):267-81. Acta Haematol. 1996;95(1):66-9.
found that the catechol flavonoids rutin and quercetin are able to suppress redox- active labile plasma iron (LPI) in both buffered solution and in iron-overloaded sera. Both flavonoids are effective in loading the metal into the iron-transport protein transferrin. • Iron derivatives of quercetin and rutin are able to permeate cell membranes, however, only free quercetin is able to gain access to the cytosol and decrease intracellular labile iron pools. J Inorg Biochem. 2012 Feb;107(1):34-9.
zinc by a human intestinal cell line Addition inositol phosphates (IP3, IP4, IP5 or IP6) decreased Fe solubility by 13 to 25% and reduced Fe uptake by 50 to 65%. • Inositol hexakisphosphate (IPo)5 or phytate is present in cereal grains and legumes and has been implicated as a significant inhibitor of Fe absorption by humans. J Nutr. 1994 Apr;124(4):580-7.
vitro, curcumin chelates metal ions. Curcumin penetrates yeast cells, concentrates in the endoplasmic reticulum (ER) membranes, and reduces the intracellular iron pool. • A delay in cell cycle progression could, in part, explain the antitumorigenic properties associated with curcumin. Eukaryot Cell. 2011 Nov;10(11):1574-81.
livers of iron-challenged thalassemic mice. Green tea (Camellia sinensis) catechins exhibit anti-oxidation, the inhibition of carcinogenesis, the detoxification of [hepatic] cells and iron chelation. Green tea inhibits or delays the deposition of hepatic iron in regularly iron-loaded thalassemic mice effectively. • This will prevent the iron-induced generation of free radicals via Haber-Weiss and Fenton reactions, and consequently liver damage and fibrosis. Med Chem. 2010 Mar;6(2):57-64.
pteroymonoglutamic acid is predominantly found in leafy green vegetables such as spinach, asparagus, and broccoli. • Unlike iron, which is required for multiple processes, the primary role of folic acid is the generation of single-carbon groups for transfer to various compounds. Annu. Rev. Nutr. 2004. 24:433–53
for folic acid has revolved around the effects of DNA methylation on cellular growth and function. • DNA methylation involves the transfer of methyl groups by DNA methyltransferases onto cytosine- guanine (CpG) dinucleotide-rich regions, most often found in gene promoters or initial exons. Annu. Rev. Nutr. 2004. 24:433–53
expression. • Hypermethylation tends to decrease gene expression and transcription, whereas hypomethylation can result in increased transcript expression. Annu. Rev. Nutr. 2004. 24:433–53
may increase genomic stability as it protects the DNA from nucleases. • Thus decreased DNA methylation can result in aberrant gene expression and increased mutability of certain genes that may give rise to uncontrolled cellular growth. Annu. Rev. Nutr. 2004. 24:433–53
a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue homeostasis. http://en.wikipedia.org/wiki/Cell_signaling
cellular Cancer often arises when normal cellular growth goes awry due to defects in critical growth goes awry due to defects in critical signal transduction pathways. signal transduction pathways. Genes Dev. 2012 Apr 1;26(7):641-50.
a transcription factor that resides in the cytoplasm of every cell and translocates to the nucleus when activated. Ann N Y Acad Sci. 2005 Nov;1056:218-33. • That NF-kB activation has been linked with most diseases is not too surprising considering that as many as 98% of all diseases are proinflammatory. Ann N Y Acad Sci. 2005 Nov;1056:218-33.
the expression of almost 400 different genes, which include enzymes (e.g., COX-2, 5-LOX, and iNOS), cytokines (such as TNF, IL-1, IL-6, IL-8, and chemokines), adhesion molecules, cell cycle regulatory molecules, viral proteins, and angiogenic factors. Ann N Y Acad Sci. 2005 Nov;1056:218-33. Oncogene. 2006 Oct 30;25(51):6680-4. Cardiovasc Toxicol. 2006;6(2):111-30. Nat Rev Mol Cell Biol. 2007 Jan;8(1):49-62. Oncogene. 1999 Nov 22;18(49):6842-4. Recent Prog Horm Res. 2003;58:95-130.
expression of genes that keep the cell proliferating and protect the cell from conditions that would otherwise cause it to die via apoptosis. Nature. 2006 May 25;441(7092):431-6.
transformation, proliferation, invasion, and angiogenesis of tumor cells. VEGF and adhesion molecules required for angiogenesis and metastasis are also regulated by NF-kB. Chemoresistance and radioresistance have also been linked to NF-kB activation. Ann N Y Acad Sci. 2005 Nov;1056:218-33.
cigarette smoke extract induced NF-kB DNA binding. Such an inhibition was accompanied by a decrease in cigarette smoke extract induced ROS production expression. • These findings provide novel data on new molecular mechanisms by which lycopene regulates cigarette smoke- driven inflammation in human macrophages. PLoS One. 2011;6(5):e19652.
cancer is significantly lower in regions where turmeric is heavily consumed. Turmeric inhibited NF-κB activation and down- regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1) , proliferation (cyclin D1 and c-Myc) , and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Mol Nutr Food Res. 2012 Mar;56(3):454-65.
cancer. Curcumin regulates the inflammatory response through the inhibition of pro-inflammatory mediators and the NF-kappaB signaling pathway. • Curcumin appears thus as a non-toxic alternative for prostate cancer prevention, treatment or co-treatment. Genes Nutr. 2010 Mar;5(1):61-74.
retinoic acid (ATRA) is considered as a potent chemotherapeutic drug for its capability of regulating cell growth and differentiation. • ATRA enters into the nucleus and regulates various signaling pathways viz. Integrin, FAK, ERK, PI-3K, NF-κB and also EGFR and down regulates pro-MMP-9 activity as well as its expression. Cell Adh Migr. 2010 Jul-Sep;4(3):409-18.
anticancer agent has begun to emerge. • The antiinflammatory effects of silymarin are mediated through suppression of NF-kappaB-regulated gene products, including COX-2, 5-LOX, TNF and IL-1. Anticancer Res. 2006 Nov-Dec;26(6B):4457-98.
component of green tea and is primarily responsible for the green tea effect. EGCG possesses two triphenolic groups in its structure which are reported to be important with respect to anticarcinogenic and antioxidant effects. • EGCG also attenuated the expression of cyclooxygenase-2 and activation of nuclear factor- kappaB induced by IL-1beta. J Nutr Biochem. 2007 Sep;18(9):587-96
that we are the key, in the end we are always told that we are the key, we each of us, as a foundational dynamic of life, we each of us, as a foundational dynamic of life, have to find all the ways we fit in the lock.” have to find all the ways we fit in the lock.” ~ David Whyte ~ ~ David Whyte ~
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