Welcome, Guest. Please login or register.
November 28, 2021, 10:48:30 pm

Login with username, password and session length

 

Members
Stats
  • Total Posts: 327
  • Total Topics: 183
  • Online Today: 32
  • Online Ever: 518
  • (January 21, 2020, 05:24:49 pm)
Users Online
Users: 0
Guests: 10
Total: 10

Welcome!

Welcome to the Cancer Health Forums, a round-the-clock discussion area for people who have any type of cancer, their friends and family and others with questions about living with cancer. Check in frequently to read what others have to say, post your comments, and hopefully learn more about how you can reach your own health goals.

Privacy Warning: Please realize that these forums are open to all, and are fully searchable via Google and other search engines. If this concerns you, then do not use a username or avatar that are self-identifying in any way. We do not allow the deletion of anything you post in these forums, so think before you post.
  • The information shared in these forums, by moderators and members, is designed to complement, not replace, the relationship between an individual and his/her own physician.
  • All members of these forums are, by default, not considered to be licensed medical providers. If otherwise, users must clearly define themselves as such.
  • Product advertisement (including links); banners; and clinical trial, study or survey participation—is strictly prohibited by forums members unless permission has been secured from the Cancer Health Forum Moderators.
Finished Reading This? You can collapse this or any other box on this page by clicking the symbol in each box.

Show Posts

This section allows you to view all posts made by this member. Note that you can only see posts made in areas you currently have access to.


Messages - danialthomas

Pages: [1] 2 3 4
1
Cancer Research News & Studies / Eggplant To The Rescue
« on: November 18, 2021, 11:29:20 am »
This will be my last posting for a while. I will be extra busy as I am going back to “school” by doing a fellowship in Metabolic Cardiology under the direction of Drs. Stephen Sinatra and Mark Houston. The focus of my practice will still be metabolic medicine and integrative cancer therapeutics, but because we are dependent on blood flow for the delivery of most medical interventions, the valuable knowledge I will gain in the cardiology fellowship will help improve our cancer treatment outcomes even further.

Many of the patients that I see have aggressive, late-stage cancer that is responding poorly or has stopped responding to conventional treatment, including trial drugs. These patients have an exceedingly strong desire to live and are not mentally ready to throw in the towel and call Hospice. Therefore, I must continually pore over the latest scientific literature in search of potentially life-saving therapeutic strategies to offer these patients. In previous postings, I have written about many of these strategies. Two medicinal plant compounds that currently have me intrigued and look promising are solamargine and solasonine.

Found in eggplant, solamargine and solasonine appear to have the fol¬lowing unique and highly desirable characteristics:

• Rapidly induces cell cycle arrest and apoptosis (cell death) in a wide variety of malignancies.
• Greater cytotoxic effects on cancer cells compared to many standard chemo-therapy drugs with negligible effect on normal cells.
• Ability to treat tumors that have become multi-drug resistant.
• Inhibits the ability of tumors to metastasize by blocking epithelial-mesenchymal transition (EMT).
• Targets active and quiescent (dormant) cancer cells, as well as cancer stem cells. Chemotherapy is designed to affect rapidly proliferating cells. To resist the effects of chemotherapy, cancer cells can stop proliferating and go into a state of dormancy, and later “wake up” and begin proliferating again.
• May stimulate lasting immunity against cancer.

Solamargine and solasonine are not commercially available at any retail or com-pounding pharmacy. Because of this, we had medicinal chemists custom synthesize these compounds for us from scratch and purify them to pharmaceutical levels. Starting next year, in select patients, we will administer a 50/50 mix of solamargine and solasonine intravenously to assure full bioavailability and prevent possible biochemical alteration by stomach acids and gut bacteria from oral administration. We will also apply administer hyperthermia to change the characteristics of the cancer cells and sensitize them to the effects of solamargine and solasonine and increase tumor blood flow to deliver more of the compounds into the tumors.

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

For more information:
Alshaibi HF, Al-Shehri B, Hassan B, Al-Zahrani R, Assiss T. Modulated Electrohyperthermia: A New Hope for Cancer Patients. Biomed Res Int. 2020 Nov 13;2020:8814878.
Cham, B. (2013) Drug therapy: Solamargine and other solasodine rhamnosyl gly¬cosides as anticancer agents. Modern Chemotherapy, 2, 33-49.
Cham, B.E. (2017) Solasodine, Solamargine and Mixtures of Solasodine Rhamno¬sides: Pathway to Expansive Clinical Anticancer Therapies. International Journal of Clinical Medicine, 8, 692-713.
Mayank, Jaitak V. Molecular docking study of natural alkaloids as multi-targeted hedgehog pathway inhibitors in cancer stem cell therapy. Comput Biol Chem. 2016 Jun;62:145-54.
S.S.S. Al Sinani, E.A. Eltayeb. The steroidal glycoalkaloids solamargine and solasonine in Solanum plants. South African Journal of Botany, Vol. 112, 2017, 253-269.

Disclaimer:
This information is for educational purposes only and not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your doctor. Therefore, I cannot answer questions regarding appropriateness in your situation, nor give dosages or treatment advice. That is for your personal doctor to determine after he or she carefully studies the references above.

2
Cancer Research News & Studies / My Personal Cancer-Prevention Strategy
« on: November 12, 2021, 04:05:00 pm »
As an expert in integrative cancer therapy, my job is to address crucial areas of care that are being neglected by mainstream medicine. At present, conventional oncology has no real strategy to offer cancer survivors to reduce the risk of disease recurrence after remission is achieved. To properly address this urgent and unmet need, because increasing age is the most significant risk factor for cancer, I had to become an expert in anti-aging medicine. A growing body of evidence strongly supports the hypothesis that by slowing the aging process, we may delay or prevent the onset or recurrence of cancer and other chronic diseases.

I view life as a precious gift and good health as our greatest asset. I embrace this view because I love life and want to live as long and as healthy as possible. I reject the notion that chronic disease and physical deterioration are an inevitable part of getting older. Below are the proactive, science-based steps that I take to:

• Stay energetic, fit, and mentally sharp
• Overcome many of the biological constraints that limit our ability to slow the aging process and extend lifespan beyond the average of 78.7 years (https://www.cdc.gov/nchs/fastats/life-expectancy.htm) and possibly beyond the “maximum” of 122 years (https://www.guinnessworldrecords.com/.../oldest-person...)
• Increase resilience against “age-associated diseases,” including cancer, heart attack, congestive heart failure, stroke, hypertension, obesity, type 2 diabetes, chronic kidney disease, osteoarthritis, osteoporosis, chronic obstructive pulmonary disease, pulmonary fibrosis, frequent infections, autoimmunity, cataracts, glaucoma, macular degeneration, depression, Alzheimer’s disease, Parkinson’s disease, chronic fatigue, and frailty

STEP 1: Cultivate a healthy lifestyle
• Eat an organic, whole-foods, low-methionine, nutrient-dense diet
• Strength-training 3 days per week and brisk walking on the other days
• Drink plenty of pure water
• Maintain gut health
• Don’t smoke or drink
• Get sound sleep
• Spend time outdoors
• Cultivate a spirit of playfulness and gratitude

STEP 2: Maintain optimal bloodwork
• Cholesterol: 140-160 mg/dL
• LDL: <100 mg/dL
• HDL: ≥60 mg/dL
• Triglycerides: <100 mg/dL
• Cortisol (stress hormone): ≤12 µg/dL
• Fibrinogen (blood clot potential): ≤275 mg/dL
• hs-CRP (silent inflammation): ≤0.5 mg/L
• Homocysteine (methylation): ≤7.5 µmol/L
• Fasting glucose: 65-85 mg/dL
• Fasting insulin: ≤5 µIU/mL
• GlycoMark® (absence of post-mealtime glucose spiking): ≥20 µg/mL
• Hemoglobin A1c (average glucose level for the last 90 days): ≤5.2%
• Ferritin (iron): 30-50 ng/mL
• Vitamin D: 40-60 ng/mL

STEP 3: Eliminate senescent cells and decrease their toxic secretions
Cellular senescence is an age-related process in which older cells stop dividing to create healthy new cells. This leads to the deterioration of tissues and organs and manifests in various diseases, such as arthritis, osteoporosis, heart disease, cancer, diabetes, frailty, and dementia. Senescent cells accumulate over time and secrete copious amounts of pro-inflammatory molecules and protein-degrading compounds that drive tissue damage and physical decline. In a vicious cycle, senescent cells induce the senescence of surrounding healthy cells through a “bystander” effect, which leads to more senescent cells and further degradation of one’s health and longevity.

Many scientists believe that by eliminating as many senescent cells as possible and suppressing the secretion of the harmful compounds from the remaining senescent cells (collectively known as “senotherapy”), we could lead a more disease-free life, enjoy a more youthful vigor, and extend lifespan. Based on the latest science, to eliminate senescent cells, I take a “senolytic” cocktail consisting of prescription dasatinib, bioavailable quercetin and fisetin, and FOXO4-DRI peptide. To decrease the toxic secretions of those senescent cells that cannot be eliminated, I take a “senomorphic” (also known as “senostatic”) cocktail of prescription rapamycin, specialized pro-resolving mediators, tocotrienols, and bioavailable apigenin and melatonin.

STEP 4: Boost the effects of fasting
A growing body of scientific literature has shown that fasting (prolonged calorie restriction) can lead to longer and healthier lives. Most of the physiological effects of fasting emanate from the following mechanisms:
Increased AMPK activity: Adenosine monophosphate-activated protein kinase (AMPK) is an enzyme that is involved in several longevity pathways and plays a key role in energy metabolism, insulin sensitivity, inflammation control, DNA repair, and muscle performance. Increasing AMPK activity reduces the risk of heart attack, stroke, hypertension, obesity, diabetes, osteoporosis, cancer, and Alzheimer’s disease.
Decreased mTOR signaling: Mechanistic target of rapamycin (mTOR) is a central regulator of cell metabolism, growth, proliferation, and survival. When mTOR is constantly elevated, it triggers numerous harmful events that increase the risk of age-associated diseases.
Increased autophagy and mitophagy: Autophagy and mitophagy are the natural cleansing processes the body uses to remove accumulated cellular waste and damaged mitochondria that interfere with normal cell function. Autophagy and mitophagy decline with age, causing cells to be damaged at an increasing rate, resulting in numerous age-related diseases. Studies have shown that stimulating autophagy and mitophagy leads to improvements in health and longevity.
Upregulation of sirtuins: Sirtuins are a family of proteins that play important regulatory roles in numerous cellular functions. Sirtuins impact the body’s inflammatory balance, cellular growth, circadian rhythms, energy metabolism, neuronal function, and stress resistance. Sirtuins counteract age-related declines in brain function, help maintain healthy blood sugar and lipid levels, and preserve muscle mass and exercise capacity.
Increased NAD+ levels: Oxidized nicotinamide adenine dinucleotide (NAD+) is a coenzyme crucial to cellular energy production. This coenzyme is found in every cell of the body and is necessary to make ATP (adenosine triphosphate)—the compound the body uses for fuel. Declining NAD+ levels are directly associated with aging. This leads to impaired mitochondrial function, resulting in numerous age-related diseases. NAD+ is also needed to activate sirtuins. Restoring NAD+ to more youthful levels can help rejuvenate an aging body and improve resistance to disease.
Inhibiting NF-κB: Where there is aging there is chronic inflammation. The relationship is so intimate that scientists have coined the term “inflammaging.” This refers to the ongoing, low-grade inflammation that occurs as we grow older. It promotes the development of age-related disease. If we can disrupt this type of inflammation, we can slow and help reverse a chief cause of degenerative aging. Scientists uncovered a key gene-regulating protein complex called Nuclear Factor-Kappa B (NF-κB). NF-κB is a primary driver of inflammation and inhibiting its production can reverse chronic inflammation and its negative effects.
To experience the benefits of fasting, I refrain from eating for 16 hours a day, limit my window period of eating to 6 hours, and have two meals per day: one at 12:00 noon and the other at 6:00 pm. As an alternative, I have 9 hours of fasting in between my two meals and eat at 10:00 am and 7:00 pm. I avoid snacking between meals. Based on the latest science, to amplify the above molecular pathways, I take a calorie-restriction-mimetic cocktail of hydroxycitrate, bioavailable curcumin, luteolin, nicotinamide riboside, piperlongumine, pterostilbene, spermidine, and white willow bark extract.

STEP 5: Reset genes
With aging, there is an increase in the expression of genes that promote inflammation, oxidative stress, insulin resistance, cancer, and tissue deterioration, along with a simultaneous decrease in the expression of genes that inhibit inflammation, oxidative stress, and cancer, and promote insulin sensitivity, DNA repair, and removal of damaged proteins. One of the most significant scientific discoveries in decades, in my opinion, was the discovery of a human tripeptide called GHK (glycyl-L-histidyl-L-lysine) that was found to reset gene expression of human cells to a healthier state. This opened the door to a whole new way to prevent and treat age-related diseases and restore a more youthful state of health. Based on this promising scientific data, I take GHK administered as a painless microinjection.

STEP 6: Restore youthful immune function
Immunosenescence is the term that refers to the progressive decline in immune function brought on by advancing age. It underlies many of the diseases of aging. It also accelerates the aging process by causing a state of hyper-inflammation that damages neurons, blood vessels, and joints. Immunosenescence also increases the risk of cancer as well as frequent and severe infections. To live a longer and healthier life, our immune system must be able to function at peak performance. Based on the latest science, I use a combination of Cistanche extract, curcumin, melatonin, Pu-erh tea, reishi mushroom, sermorelin, and low-dose naltrexone to target immunosenescence. These compounds have been found to improve immune function by various and complementary mechanisms.

STEP 7: Regenerate the endothelial glycocalyx
The endothelial glycocalyx is the slippery gel-like layer that coats the inside of our 60,000 miles of blood vessels. It is the protector of our vascular system and vital to maintaining good circulatory health. By age 40, the glycocalyx begins to deteriorate (thin). This increases the risk of hypertension, heart disease, stroke, erectile dysfunction, diabetes, loss of visual acuity, kidney disease, dementia, weakened immunity, inflammatory disorders, and cancer metastasis. To reverse the deterioration (thinning) of the endothelial glycocalyx layer, I take rhamnan sulfate, a natural compound derived from the edible seaweed Monostroma nitidum found to regenerate a healthy (thick) endothelial glycocalyx.

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

For more information:
Ashrafizadeh M, Ahmadi Z, Farkhondeh T, Samarghandian S. Autophagy regulation using luteolin: new insight into its anti-tumor activity. Cancer Cell Int. 2020 Nov 4;20(1):537.
Bagherniya M, Butler AE, Barreto GE, Sahebkar A. The effect of fasting or calorie restriction on autophagy induction: A review of the literature. Ageing Res Rev. 2018 Nov;47:183-197.
Baar MP, Brandt RMC, Putavet DA, Klein JDD, Derks KWJ, Bourgeois BRM, Stryeck S, Rijksen Y, van Willigenburg H, Feijtel DA, van der Pluijm I, Essers J, van Cappellen WA, van IJcken WF, Houtsmuller AB, Pothof J, de Bruin RWF, Madl T, Hoeijmakers JHJ, Campisi J, de Keizer PLJ. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. 2017 Mar 23;169(1):132-147.e16.
Blagosklonny MV. From rapalogs to anti-aging formula. Oncotarget. 2017;8(22):35492-35507.
Brown N, Panksepp J. Low-dose naltrexone for disease prevention and quality of life. Med Hypotheses. 2009 Mar;72(3):333-7.
Castello L, Froio T, Maina M, Cavallini G, Biasi F, Leonarduzzi G, Donati A, Bergamini E, Poli G, Chiarpotto E. Alternate-day fasting protects the rat heart against age-induced inflammation and fibrosis by inhibiting oxidative damage and NF-kB activation. Free Radic Biol Med. 2010 Jan 1;48(1):47-54.
Chan EWC, Wong CW, Tan YH, Foo JPY, Wong SK, Chan HT. Resveratrol and pterostilbene: A comparative overview of their chemistry, biosynthesis, plant sources and pharmacological properties. J Appl Pharm Sci, 2019; 9(07):124–129.
de Jesus Raposo MF, de Morais AM, de Morais RM. Marine polysaccharides from algae with potential biomedical applications. Mar Drugs. 2015 May 15;13(5):2967-3028.
Gill BS, Sharma P, Kumar R, Kumar S. Misconstrued versatility of Ganoderma lucidum: a key player in multi-targeted cellular signaling. Tumour Biol. 2016 Mar;37(3):2789-804.
Hickson LJ, Langhi Prata LGP, Bobart SA, Evans TK, Giorgadze N, Hashmi SK, Herrmann SM, Jensen MD, Jia Q, Jordan KL, Kellogg TA, Khosla S, Koerber DM, Lagnado AB, Lawson DK, LeBrasseur NK, Lerman LO, McDonald KM, McKenzie TJ, Passos JF, Pignolo RJ, Pirtskhalava T, Saadiq IM, Schaefer KK, Textor SC, Victorelli SG, Volkman TL, Xue A, Wentworth MA, Wissler Gerdes EO, Zhu Y, Tchkonia T, Kirkland JL. Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine. 2019 Sep;47:446-456.
Hurria A, Jones L, Muss HB. Cancer Treatment as an Accelerated Aging Process: Assessment, Biomarkers, and Interventions. Am Soc Clin Oncol Educ Book. 2016;35:e516-22.
Imai SI, Guarente L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech Dis. 2016;2:16017. Published 2016 Aug 18.
Ismail IA, El-Bakry HA, Soliman SS. Melatonin and turmeric ameliorate aging-induced changes: implication of immunoglobulins, cytokines, DJ-1/NRF2 and apoptosis regulation. Int J Physiol Pathophysiol Pharmacol. 2018;10(2):70-82.
Kim EC, Kim JR. Senotherapeutics: emerging strategy for healthy aging and age-related disease. BMB Rep. 2019;52(1):47-55.
Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. J Intern Med. 2020 Nov;288(5):518-536.
Madeo F, Carmona-Gutierrez D, Hofer SJ, Kroemer G. Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential. Cell Metab. 2019 Mar 5;29(3):592-610.
Malavolta M, Pierpaoli E, Giacconi R, Basso A, Cardelli M, Piacenza F, Provinciali M. Anti-inflammatory Activity of Tocotrienols in Age-related Pathologies: A SASPected Involvement of Cellular Senescence. Biol Proced Online. 2018 Nov 20;20:22.
Machin DR, Phuong TT, Donato AJ. The role of the endothelial glycocalyx in advanced age and cardiovascular disease. Curr Opin Pharmacol. 2019;45:66-71.
Mehmel M, Jovanović N, Spitz U. Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Nutrients. 2020;12(6):1616.
Pazoki-Toroudi H, Amani H, Ajami M, Nabavi SF, Braidy N, Kasi PD, Nabavi SM. Targeting mTOR signaling by polyphenols: A new therapeutic target for ageing. Ageing Res Rev. 2016 Nov;31:55-66.
Perrott KM, Wiley CD, Desprez PY, Campisi J. Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells. Geroscience. 2017 Apr;39(2):161-173.
Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018;27(3):529-547.
Rymut N, Heinz J, Sadhu S, Hosseini Z, Riley CO, Marinello M, Maloney J, MacNamara KC, Spite M, Fredman G. Resolvin D1 promotes efferocytosis in aging by limiting senescent cell-induced MerTK cleavage. FASEB J. 2020 Jan;34(1):597-609.
Shakeri F, Bianconi V, Pirro M, Sahebkar A. Effects of Plant and Animal Natural Products on Mitophagy. Oxid Med Cell Longev. 2020 Mar 10;2020:6969402.
Suzuki K, Terasawa M. Biological Activities of Rhamnan Sulfate Extract from the Green Algae Monostroma nitidum (Hitoegusa). Mar Drugs. 2020 Apr 24;18(4):228.
Thomas R, Wang W, Su DM. Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging. Immun Ageing. 2020 Jan 20;17:2.
Walker RF. Sermorelin: a better approach to management of adult-onset growth hormone insufficiency?. Clin Interv Aging. 2006;1(4):307-308.
Wang R, Yu Z, Sunchu B, Shoaf J, Dang I, Zhao S, Caples K, Bradley L, Beaver LM, Ho E, Löhr CV, Perez VI. Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism. Aging Cell. 2017 Jun;16(3):564-574.
Wang Y, Wang JW, Xiao X, Shan Y, Xue B, Jiang G, He Q, Chen J, Xu HG, Zhao RX, Werle KD, Cui R, Liang J, Li YL, Xu ZX. Piperlongumine induces autophagy by targeting p38 signaling. Cell Death Dis. 2013 Oct 3;4(10):e824.
Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, Ling YY, Melos KI, Pirtskhalava T, Inman CL, McGuckian C, Wade EA, Kato JI, Grassi D, Wentworth M, Burd CE, Arriaga EA, Ladiges WL, Tchkonia T, Kirkland JL, Robbins PD, Niedernhofer LJ. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018 Oct;36:18-28.
Yu S, Wang X, Geng P, Tang X, Xiang L, Lu X, Li J, Ruan Z, Chen J, Xie G, Wang Z, Ou J, Peng Y, Luo X, Zhang X, Dong Y, Pang X, Miao H, Chen H, Liang H. Melatonin regulates PARP1 to control the senescence-associated secretory phenotype (SASP) in human fetal lung fibroblast cells. J Pineal Res. 2017 Aug;63(1).
Zemel MB, Kolterman O, Rinella M, Vuppalanchi R, Flores O, Barritt AS 4th, Siddiqui M, Chalasani N. Randomized Controlled Trial of a Leucine-Metformin-Sildenafil Combination (NS-0200) on Weight and Metabolic Parameters. Obesity (Silver Spring). 2019 Jan;27(1):59-67.
Zhang K, Ma X, He W, Li H, Han S, Jiang Y, Wu H, Han L, Ohno T, Uotsu N, Yamaguchi K, Ma Z, Tu P. Extracts of Cistanche deserticola Can Antagonize Immunosenescence and Extend Life Span in Senescence-Accelerated Mouse Prone 8 (SAM-P8) Mice. Evid Based Complement Alternat Med. 2014;2014:601383.
Zhang L, Shao WF, Yuan LF, Tu PF, Ma ZZ. Decreasing pro-inflammatory cytokine and reversing the immunosenescence with extracts of Pu-erh tea in senescence accelerated mouse (SAM). Food Chem. 2012 Dec 15;135(4):2222-8.
Zhu M, Meng P, Ling X, Zhou L. Advancements in therapeutic drugs targeting of senescence. Ther Adv Chronic Dis. 2020 Oct 13;11:2040622320964125.

Disclaimer:
This information is for educational purposes only and not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your doctor. Therefore, I cannot answer questions regarding appropriateness in your situation, nor give brand names, dosages, or treatment advice. That is for your personal doctor to determine after he or she carefully studies the references above.

3
Cancer cells have defects in executing cell death. To enable growth, cancer cells demand higher levels of iron and lipid metabolism than normal cells. Fortunately, this also makes cancer cells more vulnerable to ferroptosis. Studies have revealed the interaction of ferroptosis and lipid metabolism in the initiation, development, invasion, metastasis, and treatment-resistance of cancer.

Because of the interaction of lipid metabolism and ferroptosis, I do not recommend taking supplements and/or repurposed drugs that inhibit lipid metabolism in cancer cells. Doing so may block ferroptosis and its ability to eradicate cancer cells and cancer stem cells.

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

Disclaimer:

This information is for educational purposes only and not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your doctor. Therefore, I cannot answer questions regarding appropriateness in your situation nor give treatment advice.

4
Having devoted a major portion of my 34-year medical career to reading the scientific literature, I have gotten to know some of the world’s leading oncobiologists. Sometimes I come across scientists whose findings from animal studies look so promising and so compelling, they cry out to be implemented in humans, especially when a stage-4 cancer patient is running out of options. One such finding has to do with senescence cancer cells and the argument against low-dose chemotherapy.

Not all cancer cells can be forced into apoptosis (programmed cell death) when treated with chemotherapy. Instead of dying outright, many cancer cells simply stop proliferating, come to a standstill, and enter a senescent or dormant-like state. This is called senescence-associated growth arrest (SAGA), and while it sounds good, it is accompanied by something bad called senescence-associated secretory phenotype (SASP) in which the senescent cancer cells secrete copious amounts of pro-inflammatory molecules, protein-degrading compounds, and cancer-promoting growth factors. These harmful compounds can stimulate cancer stem cells which can repopulate the tumor with new cancer cells.

Many chemotherapy drugs act as “senogenic” agents, meaning, they induce senescence in cancer cells. However, when combined with “senolytic” drugs, meaning, repurposed drugs shown to eradicate senescent cells, scientists found this to be a novel and powerful “one-two punch” to quickly eradicate cancer cells. In other words, using chemotherapy to create senescent cancer cells, then killing them using senolytic drugs. Two such prescription senolytic drugs that are readily available are dasatinib and digoxin. Interestingly, the scientists found that only standard doses of chemotherapy were able to induce senescence in cancer cells. When lower doses of chemotherapy were used, they were unable to induce senescence. And without the presence of senescent cancer cells, senolytic drugs have no target to treat and are therefore unable to achieve the desired result, that is, the death of cancer cells.

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

For more information:

Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. J Intern Med. 2020 Nov;288(5):518-536.
Triana-Martínez F, Picallos-Rabina P, Da Silva-Álvarez S, Pietrocola F, Llanos S, Rodilla V, Soprano E, Pedrosa P, Ferreirós A, Barradas M, Hernández-González F, Lalinde M, Prats N, Bernadó C, González P, Gómez M, Ikonomopoulou MP, Fernández-Marcos PJ, García-Caballero T, Del Pino P, Arribas J, Vidal A, González-Barcia M, Serrano M, Loza MI, Domínguez E, Collado M. Identification and characterization of Cardiac Glycosides as senolytic compounds. Nat Commun. 2019 Oct 21;10(1):4731.

Disclaimer:

This information is for educational purposes only and not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your doctor. Therefore, I cannot answer questions regarding appropriateness in your situation nor give treatment advice. That is for your doctor to determine after he or she carefully studies the references above. Your doctor also needs to be very familiar with the narrow therapeutic index of digoxin.

5
Cancer Research News & Studies / Lithium
« on: October 11, 2021, 03:51:44 pm »
To help induce iron-mediated death of cancer cells (ferroptosis), besides blocking the ferroptosis-inhibiting carbonic anhydrase #9 (CAIX) protein, it is important to target the lymphatic system. Cancer cells often metastasize regionally through the lymphatic system before they metastasize systemically through the bloodstream. Exposure to lymph fluid has been found to protect cancer cells from ferroptosis and increase their ability to survive during subsequent metastasis through the blood. Differences between lymph fluid and blood plasma that may contribute to this include higher levels of glutathione and oleic acid and less iron in lymph fluid.

To help suppress the metastatic potential of cancer cells via the lymphatic system and promote ferroptosis, lithium has been found to:

a) decrease lymphatic density and surface contact with cancer cells
b) inhibit the migration of cancer cells to the lymphatic system
c) decrease lymphatic permeability, thereby inhibiting cancer cells from entering or exiting the lymphatic system.

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

References:

1. Chafe S, Vizeacoumar F, Venkateswaran G, Nemirovsky O, Awrey S, et.al. Genome-wide synthetic lethal screen unveils novel CAIX-NFS1/xCT axis as a targetable vulnerability in hypoxic solid tumors. Science Advances. 27 Aug 2021: Vol. 7, No. 35, eabj0364.
2. Ubellacker JM, Tasdogan A, Ramesh V, Shen B, Mitchell EC, Martin-Sandoval MS, Gu Z, McCormick ML, Durham AB, Spitz DR, Zhao Z, Mathews TP, Morrison SJ. Lymph protects metastasizing melanoma cells from ferroptosis. Nature. 2020 Sep;585(7823):113-118.
3. Maeng YS, Lee R, Lee B, Choi SI, Kim EK. Lithium inhibits tumor lymphangiogenesis and metastasis through the inhibition of TGFBIp expression in cancer cells. Sci Rep. 2016 Feb 9;6:20739.

Disclaimer:

This information is for educational purposes only and not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your doctor. Therefore, I cannot answer questions regarding appropriateness in your situation nor give treatment advice. That is for your doctor to determine after he or she carefully studies the references above.

6
Cancer Research News & Studies / Targeting Tumor Hypoxia
« on: October 06, 2021, 06:12:29 pm »
As a tumor grows, it soon outstrips its blood supply, necessitating the formation of new blood vessels to continue to deliver oxygen and nutrients to the tumor. To orchestrate this, cancer cells boost the production of growth factors such as VEGF (vascular endothelial growth factor) to stimulate the formation of blood vessels in a process known as angiogenesis. Unlike the carefully formed and functional blood vessels in healthy tissue, tumor blood vessels tend to be malformed and dysfunctional. As a result, blood flow in tumors is non-uniform and erratic. Some regions of the tumor will be non-hypoxic (sufficiently oxygenated), whereas other regions will be hypoxic (oxygen-deprived).

One of the main reasons that people die prematurely of late-stage cancer is treatment failure due to treatment resistance. It turns out, tumor hypoxia plays a central role in limiting the effectiveness of anti-cancer therapy. Tumor hypoxia stimulates the formation of and stabilizes (activates) hypoxia-inducible factor 1-alpha (HIF-1α). Accumulation of stabilized HIF-1α promotes a whole cascade of events that promote the proliferation and survival of cancer cells and cancer stem cells, tumor invasion, metastasis, immunosuppression, drug resistance, ferroptosis resistance, and disease recurrence. To combat this, we have the following tools at our disposal to help reverse tumor hypoxia and its effects, and improve treatment outcomes:

• Acetazolamide
• Carbogen breathing
• Curcumin
• Hyperthermia
• Intravenous ozonated saline
• Pentoxifylline
• Sulforaphane
• Transdermal carbon dioxide

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

References:

Alonzi R, Padhani AR, Maxwell RJ, Taylor NJ, Stirling JJ, Wilson JI, d'Arcy JA, Collins DJ, Saunders MI, Hoskin PJ. Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans. Br J Cancer. 2009 Feb 24;100(4):644-8.
Bahrami A, Atkin SL, Majeed M, Sahebkar A. Effects of curcumin on hypoxia-inducible factor as a new therapeutic target. Pharmacol Res. 2018 Nov;137:159-169.
Elming PB, Sørensen BS, Oei AL, et al. Hyperthermia: The Optimal Treatment to Overcome Radiation Resistant Hypoxia. Cancers (Basel). 2019;11(1):60.
Fuhrmann DC, Mondorf A, Beifuß J, Jung M, Brüne B. Hypoxia inhibits ferritinophagy, increases mitochondrial ferritin, and protects from ferroptosis. Redox Biol. 2020 Sep;36:101670.
Golunski G, Woziwodzka A, Piosik J. Potential Use of Pentoxifylline in Cancer Therapy. Curr Pharm Biotechnol. 2018;19(3):206-216.
Jing X, Yang F, Shao C, Wei K, Xie M, Shen H, Shu Y. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer. 2019 Nov 11;18(1):157.
Kim DH, Sung B, Kang YJ, Hwang SY, Kim MJ, Yoon JH, Im E, Kim ND. Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells. Int J Oncol. 2015 Dec;47(6):2226-32.
Kuroda K, Yamashita M, Murahata Y, et al. Use of ozonated water as a new therapeutic approach to solve current concerns around antitumor treatment. Exp Ther Med. 2018;16(3):1597-1602.
Philip B, Ito K, Moreno-Sánchez R, Ralph SJ. HIF expression and the role of hypoxic microenvironments within primary tumours as protective sites driving cancer stem cell renewal and metastatic progression. Carcinogenesis. 2013 Aug;34(8):1699-707.
Said HM, Hagemann C, Carta F, Katzer A, Polat B, Staab A, Scozzafava A, Anacker J, Vince GH, Flentje M, Supuran CT. Hypoxia induced CA9 inhibitory targeting by two different sulfonamide derivatives including acetazolamide in human glioblastoma. Bioorg Med Chem. 2013 Jul 1;21(13):3949-57.
Takeda D, Hasegawa T, Ueha T, Imai Y, Sakakibara A, Minoda M, Kawamoto T, Minamikawa T, Shibuya Y, Akisue T, Sakai Y, Kurosaka M, Komori T. Transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo. PLoS One. 2014 Jul 2;9(7):e100530.

Disclaimer:

This information is for educational purposes only and not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your doctor. Therefore, I cannot answer questions regarding appropriateness in your situation nor give treatment advice. That is for your doctor to determine after he or she carefully studies the references above

7
Cancer Research News & Studies / The Origins Of Cancer
« on: September 19, 2021, 03:52:37 pm »
Like evolution vs. creation and the origins of life, there are two competing theories regarding the origins of cancer: Genetic mutation and metabolic dysfunction. Which of these is correct? It turns out, both are correct, and iron is at the very center. Iron dysregulation unifies the concepts embodied in both the genetic and metabolic theories of cancer.

Something called the intracellular labile iron pool (LIP) acts as a central hub in the birth of cancer and links iron metabolism to the traditional cancer hallmarks. Increases in the LIP creates reactive oxygen species (ROS) which in turn induces mitochondrial (metabolic) dysfunction. Increases in the LIP simultaneously induces genomic instability. At the end of the day, iron may be the single-most important “bad guy” that needs to be dealt with.

Due to the higher rates of proliferation and DNA synthesis in cancer cells vs. normal cells, cancer cells have greater requirements for and contain much more iron than normal cells. The extra iron is also needed, ironically, by cancer’s DNA repair pathways, enabling it to survive DNA damage induced by chemotherapeutic treatment.

So, while all this information may be fascinating, where do you go from here? How do you turn cancer’s love of iron into its worst nightmare? If you’re talking about the prevention of cancer, my suggestion is to keep your ferritin level between 30 and 50 ng/mL if you’re a woman and 50 and 75 ng/mL if you’re a man. When talking about the treatment of cancer, my suggestion is to use compounds shown to induce ferroptosis (iron-mediated cell death) and block ferroptosis-resistance as described in my previous posting.

Being a type of programmed or regulated necrosis of cells, ferroptosis has an advantage over apoptosis of being more immunogenic. Due to the release of immune-attracting damage-associated molecular patterns (DAMPs), ferroptosis recruits and activates immune cells at tumor sites. This can be enhanced by using natural compounds shown to increase the activity of dendritic cells, cytotoxic T-lymphocytes, B-lymphocytes, Natural Killer cells, and phagocytic macrophages. This too was described in my previous posting.

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

Reference:
Petronek MS, Spitz DR, Buettner GR, Allen BG. Linking Cancer Metabolic Dysfunction and Genetic Instability through the Lens of Iron Metabolism. Cancers (Basel). 2019;11(8):1077.

Disclaimer:

This information is for educational purposes only and not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your doctor. Therefore, I cannot answer questions regarding appropriateness in your situation nor give treatment advice. That is for your doctor to determine after he or she carefully studies the reference above and the information in my previous posting.

8
Besides apoptosis, other mechanisms of cancer-cell death include ferroptosis, necroptosis, and pyroptosis. This posting deals with ferroptosis. I will talk about necroptosis and pyroptosis in future postings.

The term ferroptosis was first coined in 2012 to describe the programmed cell death due to the iron-mediated overaccumulation of oxidatively-damaged, cytotoxic phospholipids called lipid peroxides. Due to the higher rates of proliferation and DNA synthesis in cancer cells vs. normal cells, cancer cells have greater requirements for and contain much more iron than normal cells. This distinct difference between cancer cells vs. normal cells can and should be exploited.

In an important study that was just published, scientists at the University of British Columbia believe they may be one step closer to defeating cancer after finding what they call the disease’s “Achilles’ heel.” Their study uncovered a protein that fuels cancer when tumor oxygen levels are low (tumor hypoxia). It enables cancer to adapt and survive and become more aggressive. This protein is called CAIX (Carbonic Anhydrase #9) and it helps cancer cells spread (metastasize) to other organs.

Cancer depends on the CAIX enzyme to survive. By inhibiting its activity, the scientists believe we can effectively stop cancer cells from growing and spreading. The CAIX enzyme effectively blocks cancer cells from ferroptosis-mediated cell death. According to one of the study authors, Dr. Shoukat Dedhar, “Combining inhibitors of CAIX, including SLC-0111, with compounds known to bring about ferroptosis results in catastrophic cell death and debilitates tumor growth.”

The scientists found that targeting CAIX acidifies intracellular pH, disrupts redox homeostasis, and creates vulnerability to ferroptosis. So, if you have metastatic cancer and desperately need new treatment options, do you wait a decade or more to see if experimental compound SLC-0111 becomes an FDA-approved drug? Do you wait while approved drugs that induce ferroptosis are developed? Or does your doctor put on or his or her “translational-research” hat and consider using natural compounds such as spermidine to inhibit CAIX and piperlongumine to induce ferroptosis? I have my answer, but your doctor will need to answer it for you after carefully studying the references provided below.

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

References:

Chafe S, Vizeacoumar F, Venkateswaran G, Nemirovsky O, Awrey S, et.al. Genome-wide synthetic lethal screen unveils novel CAIX-NFS1/xCT axis as a targetable vulnerability in hypoxic solid tumors. Science Advances. 27 Aug 2021: Vol. 7, No. 35, eabj0364.
Davis RA, Vullo D, Supuran CT, Poulsen SA. Natural product polyamines that inhibit human carbonic anhydrases. Biomed Res Int. 2014;2014:374079.
Yamaguchi Y, Kasukabe T, Kumakura S. Piperlongumine rapidly induces the death of human pancreatic cancer cells mainly through the induction of ferroptosis. Int J Oncol. 2018 Mar;52(3):1011-1022.

Disclaimer:

This information is for educational purposes only and not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your doctor. Therefore, I cannot answer questions regarding appropriateness in your situation, nor give brand names, dosages, or treatment advice. That is for your doctor to determine after they carefully study the references above.

9
Over the past 34 years, I have found that “less is more” when it comes to treating cancer. Taking too many pills not only causes nausea, vomiting, and ruined appetite, but it can also put undue burden on kidney and liver function, as well as impair bone-marrow production of blood cells.

When treating cancer, it is important that these 7 areas be included:

1. Decrease intratumoral hypoxia
2. Inhibit glucose, glutamine, and fatty-acid metabolism
3. Sensitize cancer cells to oxidative stress
4. Disable cancer’s glutathione and thioredoxin antioxidant defense systems
5. Induce apoptosis through excessive oxidative stress
6. Increase tumor-infiltrating lymphocytes and natural-killer cells
7. Promote removal of tumor debris by increasing resolvins

To keep the pill-burden low, we can accomplish the above by using the 12 items below:

1. 2-deoxy-D-glucose
2. Aspirin
3. Bromelain
4. Ganoderma lucidum
5. Molecular iodine
6. Piperlongumine
7. Propranolol
8. Pro-resolving mediators
9. Pyrroloquinoline quinone
10. Sodium selenite
11. Tocotrienols
12. Transcutaneous carbon dioxide

If you are taking a lot of pills and wish to take fewer, I encourage you to share this information with your oncologist and/or integrative/functional-medicine doctor.
Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

References:
1. Brohée L, Peulen O, Nusgens B, Castronovo V, Thiry M, Colige AC, Deroanne CF. Propranolol sensitizes prostate cancer cells to glucose metabolism inhibition and prevents cancer progression. Sci Rep. 2018 May 4;8(1):7050.
2. Chang CJ, Chen YY, Lu CC, Lin CS, Martel J, Tsai SH, Ko YF, Huang TT, Ojcius DM, Young JD, Lai HC. Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin. Innate Immun. 2014 Apr;20(3):301-11.
3. Chang TC, Wei PL, Makondi PT, Chen WT, Huang CY, Chang YJ. Bromelain inhibits the ability of colorectal cancer cells to proliferate via activation of ROS production and autophagy. PLoS One. 2019 Jan 18;14(1):e0210274.
4. Gilligan MM, Gartung A, Sulciner ML, et al. Aspirin-triggered proresolving mediators stimulate resolution in cancer. Proc Natl Acad Sci U S A. 2019;116(13):6292-6297.
5. Kieliszek M, Lipinski B, Błażejak S. Application of Sodium Selenite in the Prevention and Treatment of Cancers. Cells. 2017 Oct 24;6(4):39.
6. Min Z, Wang L, Jin J, et al. Pyrroloquinoline Quinone Induces Cancer Cell Apoptosis via Mitochondrial-Dependent Pathway and Down-Regulating Cellular Bcl-2 Protein Expression. J Cancer. 2014;5(7):609-624.
7. Mojadadi, Shafi et al. Immunomodulatory Effects of Ganoderma lucidum (W. Curt.:Fr.) P. Karst. (Aphyllophoromycetideae) on CD4+/CD8+ Tumor Infiltrating Lymphocytes in Breast-Cancer-Bearing Mice. International Journal of Medicinal Mushrooms8 (2006): 315-320.
8. Moreno-Vega A, Vega-Riveroll L, Ayala T, et al. Adjuvant Effect of Molecular Iodine in Conventional Chemotherapy for Breast Cancer. Randomized Pilot Study. Nutrients. 2019;11(7):1623.
9. Shutt DC, O’Dorisio MS, Aykin-Burns N, Spitz DR. 2-deoxy-D-glucose induces oxidative stress and cell killing in human neuroblastoma cells. Cancer Biol Ther.2010;9(11):853-861.
10. Takeda D, Hasegawa T, Ueha T, Imai Y, Sakakibara A, Minoda M, Kawamoto T, Minamikawa T, Shibuya Y, Akisue T, Sakai Y, Kurosaka M, Komori T. Transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo. PLoS One. 2014 Jul 2;9(7):e100530.
11. Tham SY, Loh HS, Mai CW, Fu JY. Tocotrienols Modulate a Life or Death Decision in Cancers. Int J Mol Sci. 2019;20(2):372.
12. Wang H, Jiang H, Corbet C, de Mey S, Law K, Gevaert T, Feron O, De Ridder M. Piperlongumine increases sensitivity of colorectal cancer cells to radiation: Involvement of ROS production via dual inhibition of glutathione and thioredoxin systems. Cancer Lett. 2019 May 28;450:42-52.
13. Zhang Q, Zhu B, Li Y. Resolution of Cancer-Promoting Inflammation: A New Approach for Anticancer Therapy. Front Immunol. 2017 Feb 2;8:71.
14. Zhao J, Zhou R, Hui K, et al. Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells. Oncotarget. 2017;8(12):18832-18847.

Disclaimer:
This information is for educational purposes only and not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your personal physician. Therefore, I cannot answer questions regarding appropriateness in your situation, nor give brand names, dosages, or treatment instructions. That is for your personal physician to determine after her or she carefully studies the references above.

10
High blood levels of the extracellular iron-storage protein called ferritin correlate with aggressive disease and poorer clinical outcomes in cancer patients. Excess extracellular iron has been found to diminish the anti-cancer effects of intravenous vitamin C (IVC). Based on this, administering IVC without considering ferritin levels is ill-advised. Excess extracellular iron decreases the intracellular uptake of vitamin C and IVC-induced production of cancer-killing, pro-oxidative hydrogen peroxide. Removal of extracellular iron using the iron-chelating drug Deferasirox was shown to improve the anti-cancer effects of IVC by promoting intracellular uptake of vitamin C and IVC-induced production of hydrogen peroxide.

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

Reference:
Tsuma-Kaneko, M., Sawanobori, M., Kawakami, S. et al. Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells. Sci Rep 8, 17377 (2018).

Disclaimer:
This information is for educational purposes only. It is not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your personal physician. Therefore, I cannot comment as to appropriateness in your situation, nor give dosages or treatment guidelines. That is for your personal physician to determine after studying the reference above

11
New research suggests that many colorectal cancers spread from the site where they first developed to other parts of the body long before the original tumor can be detected by current diagnostic tests.
We have long assumed that the spread (metastasis) of tumors occurs later in the disease process. As tumors grow and cancer cells accrue more genetic mutations, some cells develop the ability to move from the site of the primary tumor into the bloodstream or lymphatic system to spread to distant locations in the body, and grow into tumors in the new locations.
Dr. Christina Curtis from Stanford University’s School of Medicine and her team used genetic analysis of the primary colorectal tumors and the metastatic tumors from the same patients, coupled with computer simulations. The findings led them to conclude that colorectal cancer can spread soon after the original tumor appears, and likely does so years before the disease is every diagnosed. Their findings show that some cancers are capable of metastasizing right from the start.
Does this important discovery apply to cancers other than colorectal? We do not know yet, but I suspect that will be the case. To be safe, if you have been told that you have non-metastatic (stage-1 or stage-2) cancer, and you insist on doing “localized” treatment only, such as surgery or radiation, you may wish to reconsider and follow up with systemic treatment.

Comments from Dr. Thomas: Please note that this information for educational purposes only. It is not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your personal physician. Therefore, I cannot give specific treatment recommendations. That is for your personal physician to determine after studying the reference below.

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

Reference:
Hu Z, Ding J, Ma Z, Sun R, Seoane JA, Scott Shaffer J, Suarez CJ, Berghoff AS, Cremolini C, Falcone A, Loupakis F, Birner P, Preusser M, Lenz HJ, Curtis C. Quantitative evidence for early metastatic seeding in colorectal cancer. Nat Genet. 2019 Jul;51(7):1113-1122.

12
Cancer Research News & Studies / Staying Healthy After Cancer
« on: August 17, 2021, 07:29:57 pm »
Many people ask me what I recommend they should do after achieving remission to improve and maintain their health. Because I believe in leading by example. below are the proactive, science-based steps that I take and that I recommend others try to take to:

• Stay energetic, fit, and mentally sharp
• Overcome many of the biological constraints that limit our ability to slow the aging process and extend lifespan beyond the average of 78.7 years and possibly even beyond the maximum of 122
• Increase resilience against “age-associated diseases,” such as cancer, heart attack, congestive heart failure, stroke, hypertension, obesity, type 2 diabetes, chronic kidney disease, osteoarthritis, osteoporosis, chronic obstructive pulmonary disease, pulmonary fibrosis, frequent infections, autoimmunity, cataracts, glaucoma, macular degeneration, depression, dementia, Parkinson’s disease, chronic fatigue, and frailty


STEP 1: Cultivate a healthy lifestyle
• Eat an organic, whole-foods, methionine-restricted, nutrient-dense diet
• Strength-training 3 days per week and brisk walking on the other days
• Drink plenty of pure water
• Maintain gut health
• Don’t smoke or drink
• Get sound sleep
• Spend time outdoors
• Cultivate a spirit of playfulness and gratitude


STEP 2: Maintain optimal bloodwork

• Cholesterol: 140-160 mg/dL
• LDL: <100 mg/dL
• HDL: ≥60 mg/dL
• Triglycerides: <100 mg/dL
• Cortisol (stress hormone): ≤12 µg/dL
• Fibrinogen (blood clot potential): ≤275 mg/dL
• hs-CRP (silent inflammation): ≤0.5 mg/L
• Homocysteine (methylation): ≤7.5 µmol/L
• Fasting glucose: 65-85 mg/dL
• Fasting insulin: ≤5 µIU/mL
• GlycoMark® (absence of post-mealtime glucose spiking): ≥20 µg/mL
• Hemoglobin A1c (average glucose level for the last 90 days): ≤5.2%
• Ferritin (iron): 30-50 ng/mL
• Vitamin D: 40-60 ng/mL


STEP 3: Eliminate senescent cells and decrease their toxic secretions
Cellular senescence is an age-related process in which older cells stop dividing to create healthy new cells. This leads to the deterioration of tissues and organs and manifests in various diseases, such as arthritis, osteoporosis, heart disease, cancer, diabetes, frailty, and dementia. Senescent cells accumulate over time and secrete copious amounts of pro-inflammatory molecules and protein-degrading compounds that drive tissue damage and physical decline. In a vicious cycle, senescent cells induce the senescence of surrounding healthy cells through a “bystander” effect, which leads to more senescent cells and further degradation of one’s health and longevity.
Many scientists believe that by eliminating as many senescent cells as possible and suppressing the secretion of the harmful compounds from the remaining senescent cells (also known as “senotherapy”), we could lead a more disease-free life, enjoy a more youthful vigor, and extend lifespan. Based on the latest science, to eliminate senescent cells, I take a “senolytic” cocktail consisting of prescription dasatinib, bioavailable quercetin and fisetin, and FOXO4-DRI peptide. To decrease the toxic secretions of those senescent cells that cannot be eliminated, I take a “senomorphic” (also known as “senostatic”) cocktail of prescription rapamycin, specialized pro-resolving mediators, tocotrienols, and bioavailable apigenin and melatonin.


STEP 4: Boost the effects of fasting
A growing body of scientific literature has shown that fasting (prolonged calorie restriction) can lead to longer and healthier lives. Most of the physiological effects of fasting emanate from the following mechanisms:
Increased AMPK activity: Adenosine monophosphate-activated protein kinase (AMPK) is an enzyme that is involved in several longevity pathways and plays a key role in energy metabolism, insulin sensitivity, inflammation control, DNA repair, and muscle performance. Increasing AMPK activity reduces the risk of heart attack, stroke, hypertension, obesity, diabetes, osteoporosis, cancer, and Alzheimer’s disease.
Decreased mTOR signaling: Mechanistic target of rapamycin (mTOR) is a central regulator of cell metabolism, growth, proliferation, and survival. When mTOR is constantly elevated, it triggers numerous harmful events that increase the risk of age-associated diseases.
Increased autophagy and mitophagy: Autophagy and mitophagy are the natural cleansing processes the body uses to remove accumulated cellular waste and damaged mitochondria that interfere with normal cell function. Autophagy and mitophagy decline with age, causing cells to be damaged at an increasing rate, resulting in numerous age-related diseases. Studies have shown that stimulating autophagy and mitophagy leads to improvements in health and longevity.
Upregulation of sirtuins: Sirtuins are a family of proteins that play important regulatory roles in numerous cellular functions. Sirtuins impact the body’s inflammatory balance, cell growth, circadian rhythms, energy metabolism, neuronal function, and stress resistance. Sirtuins counteract age-related declines in brain function, help maintain healthy blood sugar and lipid levels, and preserve muscle mass and exercise capacity.
• Increased NAD+ levels: Oxidized nicotinamide adenine dinucleotide (NAD+) is a coenzyme crucial to cellular energy production. This coenzyme is found in every cell of the body and is necessary to make ATP (adenosine triphosphate)—the compound the body uses for fuel. Declining NAD+ levels are directly associated with aging. This leads to impaired mitochondrial function, resulting in numerous age-related diseases. NAD+ is also needed to activate sirtuins. Restoring NAD+ to more youthful levels can help rejuvenate an aging body and improve resistance to disease.
Inhibiting NF-κB: Where there is aging there is chronic inflammation. The relationship is so intimate that scientists have coined the term “inflammaging.” This refers to the ongoing, low-grade inflammation that occurs as we grow older. It promotes the development of age-related disease. If we can interrupt this type of inflammation, we can slow and help reverse a chief cause of degenerative aging. Scientists uncovered a key gene-regulating protein complex called Nuclear Factor-Kappa B (NF-κB). NF-κB is a primary driver of inflammation and inhibiting its production can reverse chronic inflammation and its negative effects.
To experience the benefits of fasting, I refrain from eating for 16 hours a day, limit my window period of eating to 6 hours, and have two meals per day: one at 12:00 noon and the other at 6:00 pm. As an alternative, I have 9 hours of fasting in between my two meals and eat at 10:00 am and 7:00 pm. I avoid snacking between meals. Based on the latest science, I take a calorie-restriction-mimetic cocktail of hydroxycitrate, bioavailable curcumin, luteolin, nicotinamide riboside to amplify the above molecular pathways, piperlongumine, pterostilbene, spermidine, and white willow bark extract.


STEP 5: Reset genes
With aging, there is an increase in the expression of genes that promote inflammation, oxidative stress, insulin resistance, cancer, and tissue deterioration, along with a simultaneous decrease in the expression of genes that inhibit inflammation, oxidative stress, and cancer, and promote insulin sensitivity, DNA repair, and removal of damaged proteins. One of the most significant scientific discoveries in decades, in my opinion, was the discovery of a human tripeptide called GHK (glycyl-L-histidyl-L-lysine) that was found to reset gene expression of human cells to a healthier state. This opened the door to a whole new way to prevent and treat age-related diseases and restore a more youthful state of health. Based on this promising scientific data, I take GHK administered as a painless microinjection.

STEP 6: Restore youthful immune function
Immuno-senescence is the term that refers to the progressive decline in immune function brought on by advancing age. It underlies many of the diseases of aging. It also accelerates the aging process itself by causing a state of hyper-inflammation that damages neurons, blood vessels, and joints. Immuno-senescence also increases the risk of cancer as well as frequent and severe infections. To live a longer and healthier life, we need our immune system to function at peak performance. Based on the latest science, I use a combination of Cistanche extract, Pu-erh tea, and reishi mushroom to target immunosenescence. These compounds have been found to improve immune function by various and complementary mechanisms.


STEP 7: Regenerate the endothelial glycocalyx
The endothelial glycocalyx is a microscopically thin, gel-like, non-stick layer that coats the inside of our 60,000 miles of blood vessels. It is the guardian of our blood vessels and key to maintaining circulatory health. By age 40, the glycocalyx begins to deteriorate. This eventually leads to a host of health issues, including hypertension, heart disease, stroke, erectile dysfunction, pre-diabetes and diabetes, loss of visual acuity, kidney disease, dementia, viral infections, and exercise intolerance. To reverse the deterioration of the endothelial glycocalyx layer, I take rhamnan sulfate—a natural compound derived from the edible seaweed Monostroma nitidum—that has been found to regenerate the endothelial glycocalyx.


Comments from Dr. Thomas: Please note that this information for educational purposes only. It is not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your personal physician. Therefore, I cannot give specific dosages or treatment guidelines. That is for your personal physician to determine after studying the references below.


Dr. Daniel Thomas, DO, MS
Mount Dora, Florida


References:
Ashrafizadeh M, Ahmadi Z, Farkhondeh T, Samarghandian S. Autophagy regulation using luteolin: new insight into its anti-tumor activity. Cancer Cell Int. 2020 Nov 4;20(1):537.
Bagherniya M, Butler AE, Barreto GE, Sahebkar A. The effect of fasting or calorie restriction on autophagy induction: A review of the literature. Ageing Res Rev. 2018 Nov;47:183-197.
Baar MP, Brandt RMC, Putavet DA, Klein JDD, Derks KWJ, Bourgeois BRM, Stryeck S, Rijksen Y, van Willigenburg H, Feijtel DA, van der Pluijm I, Essers J, van Cappellen WA, van IJcken WF, Houtsmuller AB, Pothof J, de Bruin RWF, Madl T, Hoeijmakers JHJ, Campisi J, de Keizer PLJ. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. 2017 Mar 23;169(1):132-147.e16.
Blagosklonny MV. From rapalogs to anti-aging formula. Oncotarget. 2017;8(22):35492-35507.
Castello L, Froio T, Maina M, Cavallini G, Biasi F, Leonarduzzi G, Donati A, Bergamini E, Poli G, Chiarpotto E. Alternate-day fasting protects the rat heart against age-induced inflammation and fibrosis by inhibiting oxidative damage and NF-kB activation. Free Radic Biol Med. 2010 Jan 1;48(1):47-54.
Chan EWC, Wong CW, Tan YH, Foo JPY, Wong SK, Chan HT. Resveratrol and pterostilbene: A comparative overview of their chemistry, biosynthesis, plant sources and pharmacological properties. J Appl Pharm Sci, 2019; 9(07):124–129.
de Jesus Raposo MF, de Morais AM, de Morais RM. Marine polysaccharides from algae with potential biomedical applications. Mar Drugs. 2015 May 15;13(5):2967-3028.
Gill BS, Sharma P, Kumar R, Kumar S. Misconstrued versatility of Ganoderma lucidum: a key player in multi-targeted cellular signaling. Tumour Biol. 2016 Mar;37(3):2789-804.
Hickson LJ, Langhi Prata LGP, Bobart SA, Evans TK, Giorgadze N, Hashmi SK, Herrmann SM, Jensen MD, Jia Q, Jordan KL, Kellogg TA, Khosla S, Koerber DM, Lagnado AB, Lawson DK, LeBrasseur NK, Lerman LO, McDonald KM, McKenzie TJ, Passos JF, Pignolo RJ, Pirtskhalava T, Saadiq IM, Schaefer KK, Textor SC, Victorelli SG, Volkman TL, Xue A, Wentworth MA, Wissler Gerdes EO, Zhu Y, Tchkonia T, Kirkland JL. Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine. 2019 Sep;47:446-456.
Imai SI, Guarente L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech Dis. 2016;2:16017. Published 2016 Aug 18.
Kim EC, Kim JR. Senotherapeutics: emerging strategy for healthy aging and age-related disease. BMB Rep. 2019;52(1):47-55.
Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. J Intern Med. 2020 Nov;288(5):518-536.
Madeo F, Carmona-Gutierrez D, Hofer SJ, Kroemer G. Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential. Cell Metab. 2019 Mar 5;29(3):592-610.
Malavolta M, Pierpaoli E, Giacconi R, Basso A, Cardelli M, Piacenza F, Provinciali M. Anti-inflammatory Activity of Tocotrienols in Age-related Pathologies: A SASPected Involvement of Cellular Senescence. Biol Proced Online. 2018 Nov 20;20:22.
Machin DR, Phuong TT, Donato AJ. The role of the endothelial glycocalyx in advanced age and cardiovascular disease. Curr Opin Pharmacol. 2019;45:66-71.
Mehmel M, Jovanović N, Spitz U. Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Nutrients. 2020;12(6):1616.
Pazoki-Toroudi H, Amani H, Ajami M, Nabavi SF, Braidy N, Kasi PD, Nabavi SM. Targeting mTOR signaling by polyphenols: A new therapeutic target for ageing. Ageing Res Rev. 2016 Nov;31:55-66.
Perrott KM, Wiley CD, Desprez PY, Campisi J. Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells. Geroscience. 2017 Apr;39(2):161-173.
Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018;27(3):529-547.
Rymut N, Heinz J, Sadhu S, Hosseini Z, Riley CO, Marinello M, Maloney J, MacNamara KC, Spite M, Fredman G. Resolvin D1 promotes efferocytosis in aging by limiting senescent cell-induced MerTK cleavage. FASEB J. 2020 Jan;34(1):597-609.
Shakeri F, Bianconi V, Pirro M, Sahebkar A. Effects of Plant and Animal Natural Products on Mitophagy. Oxid Med Cell Longev. 2020 Mar 10;2020:6969402.
Suzuki K, Terasawa M. Biological Activities of Rhamnan Sulfate Extract from the Green Algae Monostroma nitidum (Hitoegusa). Mar Drugs. 2020 Apr 24;18(4):228.
Wang R, Yu Z, Sunchu B, Shoaf J, Dang I, Zhao S, Caples K, Bradley L, Beaver LM, Ho E, Löhr CV, Perez VI. Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism. Aging Cell. 2017 Jun;16(3):564-574.
Wang Y, Wang JW, Xiao X, Shan Y, Xue B, Jiang G, He Q, Chen J, Xu HG, Zhao RX, Werle KD, Cui R, Liang J, Li YL, Xu ZX. Piperlongumine induces autophagy by targeting p38 signaling. Cell Death Dis. 2013 Oct 3;4(10):e824.
Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, Ling YY, Melos KI, Pirtskhalava T, Inman CL, McGuckian C, Wade EA, Kato JI, Grassi D, Wentworth M, Burd CE, Arriaga EA, Ladiges WL, Tchkonia T, Kirkland JL, Robbins PD, Niedernhofer LJ. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018 Oct;36:18-28.
Yu S, Wang X, Geng P, Tang X, Xiang L, Lu X, Li J, Ruan Z, Chen J, Xie G, Wang Z, Ou J, Peng Y, Luo X, Zhang X, Dong Y, Pang X, Miao H, Chen H, Liang H. Melatonin regulates PARP1 to control the senescence-associated secretory phenotype (SASP) in human fetal lung fibroblast cells. J Pineal Res. 2017 Aug;63(1).
Zemel MB, Kolterman O, Rinella M, Vuppalanchi R, Flores O, Barritt AS 4th, Siddiqui M, Chalasani N. Randomized Controlled Trial of a Leucine-Metformin-Sildenafil Combination (NS-0200) on Weight and Metabolic Parameters. Obesity (Silver Spring). 2019 Jan;27(1):59-67.
Zhang K, Ma X, He W, Li H, Han S, Jiang Y, Wu H, Han L, Ohno T, Uotsu N, Yamaguchi K, Ma Z, Tu P. Extracts of Cistanche deserticola Can Antagonize Immunosenescence and Extend Life Span in Senescence-Accelerated Mouse Prone 8 (SAM-P8) Mice. Evid Based Complement Alternat Med. 2014;2014:601383.
Zhang L, Shao WF, Yuan LF, Tu PF, Ma ZZ. Decreasing pro-inflammatory cytokine and reversing the immunosenescence with extracts of Pu-erh tea in senescence accelerated mouse (SAM). Food Chem. 2012 Dec 15;135(4):2222-8.
'References: P, Ling X, Zhou L. Advancements in therapeutic drugs targeting of senescence. Ther Adv Chronic Dis. 2020 Oct 13;11:2040622320964125.

13
Cancer Research News & Studies / Covid 19
« on: August 01, 2021, 10:35:09 am »
For those of you who are choosing not to get vaccinated against COVID-19, or have been vaccinated, and want to know what the recent scientific literature suggests may be helpful preventing a life-threatening infection, besides masks, social distancing, and frequent handwashing, the following compounds have been looked at:

Ivermectin plus aspirin, melatonin, quercetin, vitamin C, vitamin D, and zinc. See Kory P, Meduri GU, Varon J, Iglesias J, Marik PE. Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19. Am J Ther. 2021;28(3):e299-e318.
Zinc plus hinokitiol. See Hoang BX, Han B. A possible application of hinokitiol as a natural zinc ionophore and anti-infective agent for the prevention and treatment of COVID-19 and viral infections. Med Hypotheses. 2020 Dec;145:110333.
Bromelain plus curcumin. See Kritis P, Karampela I, Kokoris S, Dalamaga M. The combination of bromelain and curcumin as an immune-boosting nutraceutical in the prevention of severe COVID-19. Metabol Open. 2020 Dec;8:100066.
Rhamnan sulfate. See Wadowski PP, Jilma B, Kopp CW, Ertl S, Gremmel T, Koppensteiner R. Glycocalyx as Possible Limiting Factor in COVID-19. Front Immunol. 2021 Feb 22;12:607306.

Comments from Dr. Thomas: Please note that this information for educational purposes only. It is not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your personal physician. Therefore, I cannot give dosages or treatment guidelines. That is for your personal physician to determine after studying the references above.

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

14
Cancer Research News & Studies / Beyond Intravenous Vitamin C
« on: July 28, 2021, 09:36:47 am »
We know from published research that a high concentration of curcumin (turmeric extract) is effective at killing cancer cells without harming normal cells. In addition, a 5-micromolar concentration of curcumin has been found to reduce the amount of cisplatin (chemotherapy drug) needed to kill various types of cancer cells by a remarkable 300-fold.

When synergistic curcumin and low-dose cisplatin are administered as intravenous cyclodextrin-based nanoparticles, the efficacy of curcumin and cisplatin is improved even further by increasing their solubility, stability, and penetration into tumors. Further synergy is achieved by adding intravenous dichloroacetate, oral celecoxib, and hyperthermia:

• By raising the internal temperature of tumors to 43°C with medical electromagnetic hyperthermia, we sensitize cancer cells to the effects of curcumin and cisplatin and increase tumor blood flow to deliver more curcumin, cisplatin, dichloroacetate, and celecoxib deep into tumors.
• Dichloroacetate sensitizes cancer cells to the effects of hyperthermia and cisplatin.
• Curcumin sensitizes cancer cells to dichloroacetate.
• Celecoxib sensitizes cancer cells to the effects of curcumin, cisplatin, and dichloroacetate.
• Cancer cells and cancer stem cells are directly killed in the presence of sufficient heat.
• Hyperthermia triggers a potent immune response by improving immune recognition of cancer cells through the expression of heat-shock proteins (HSPs) and increasing tumor-infiltrating lymphocytes (TILs). The latter can be further enhanced with the use of oral molecular iodine and/or injectable thymosin alpha 1 (Tα1).

Please note that this information for educational purposes only. It is not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your personal physician. Therefore, I cannot give dosages or treatment guidelines for the above-mentioned items. That is for your personal physician to determine after studying the references below.

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

References:
Cheng Y, Weng S, Yu L, Zhu N, Yang M, Yuan Y. The Role of Hyperthermia in the Multidisciplinary Treatment of Malignant Tumors. Integr Cancer Ther. 2019;18:1534735419876345.
Costantini C, Bellet MM, Pariano M, et al. A Reappraisal of Thymosin Alpha1 in Cancer Therapy. Front Oncol. 2019;9:873.
Huang H, Yu K, Mohammadi A, Karanthanasis E, Godley A, Yu JS. It’s Getting Hot in Here: Targeting Cancer Stem-like Cells with Hyperthermia. J Stem Cell Transplant Biol. 2017;2(2):113.
Kan PC, Chang YJ, Chien CS, Su CY, Fang HW. Coupling Dichloroacetate Treatment with Curcumin Significantly Enhances Anticancer Potential. Anticancer Res. 2018 Nov;38(11):6253-6261.
Lev-Ari S, Strier L, Kazanov D, Madar-Shapiro L, Dvory-Sobol H, Pinchuk I, Marian B, Lichtenberg D, Arber N. Celecoxib and curcumin synergistically inhibit the growth of colorectal cancer cells. Clin Cancer Res. 2005 Sep 15;11(18):6738-44.
Li B, Li X, Xiong H, et al. Inhibition of COX2 enhances the chemosensitivity of dichloroacetate in cervical cancer cells. Oncotarget. 2017;8(31):51748-51757.
Liu B, Yan S, Qu L, Zhu J. Celecoxib enhances anticancer effect of cisplatin and induces anoikis in osteosarcoma via PI3K/Akt pathway. Cancer Cell Int. 2017;17:1.
McCubrey JA, Abrams SL, Lertpiriyapong K, Cocco L, Ratti S, Martelli AM, Candido S, Libra M, Murata RM, Rosalen PL, Lombardi P, Montalto G, Cervello M, Gizak A, Rakus D, Steelman LS. Effects of berberine, curcumin, resveratrol alone and in combination with chemotherapeutic drugs and signal transduction inhibitors on cancer cells-Power of nutraceuticals. Adv Biol Regul. 2018 Jan;67:190-211.
Moreno-Vega A, Vega-Riveroll L, Ayala T, et al. Adjuvant Effect of Molecular Iodine in Conventional Chemotherapy for Breast Cancer. Randomized Pilot Study. Nutrients. 2019;11(7):1623.
Muñoz, N.M., Minhaj, A.A., Guo, C., Michael, C., & Cressman, E. (2016). Metabolic modulation with dichloroacetate sensitizes cells to hyperthermia in human hepatocellular carcinoma cell lines. Journal of Vascular and Interventional Radiology, 27.
Qiu, N., Li, X. & Liu, J. Application of cyclodextrins in cancer treatment. J Incl Phenom Macrocycl Chem 89, 229–246 (2017).
Olszewski U, Poulsen TT, Ulsperger E, Poulsen HS, Geissler K, Hamilton G. In vitro cytotoxicity of combinations of dichloroacetate with anticancer platinum compounds. Clin Pharmacol. 2010;2:177-83.
Ralph SJ, Nozuhur S, Moreno-Sánchez R, Rodríguez-Enríquez S, Pritchard R. NSAID celecoxib: a potent mitochondrial pro-oxidant cytotoxic agent sensitizing metastatic cancers and cancer stem cells to chemotherapy. J Cancer Metastasis Treat 2018;4:49.
Syng-Ai C, Kumari AL, Khar A. Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2. Mol Cancer Ther. 2004 Sep;3(9):1101-8.
Yagawa Y, Tanigawa K, Kobayashi Y, Yamamoto M. Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery. J Cancer Metastasis Treat 2017;3:218-230.
Zhang Q, Zhu B, Li Y. Resolution of Cancer-Promoting Inflammation: A New Approach for Anticancer Therapy. Front Immunol. 2017 Feb 2;8:71.

15
Cancer Research News & Studies / Oxidizing Cancer Cells To Death
« on: June 30, 2021, 06:17:37 pm »
Cancer cells are particularly prone to oxidative stress because they are more active than normal cells, their mitochondria are often dysfunctional, and tumors possess abnormal vascular networks resulting in unstable oxygen delivery. Most conventional anti-cancer treatments, such as chemotherapy and radiation, kill cancer cells by severe oxidative stress by inducing the production of excessive reactive oxygen species (ROS). It turns out, immune cells also utilize severe oxidative stress to kill cancer cells.
Oxidative stress upregulates numerous survival mechanisms of cancer and allows tumors to grow and spread and enables them to resist the effects of treatment and evade immune attack. Oxidative stress is a double-edged sword, however, and cancer cells have their limit. The way to push cancer cells past their limit and induce apoptosis (cell death), is to impair their antioxidant defense system by depleting their stores of glutathione and thioredoxin reductase—cancer’s two main antioxidants that neutralize oxidative stress and prevent irreversible cellular oxidative damage. By depleting these antioxidants, we sensitize cancer to the deadly effects of oxidative stress by exceeding the capacity of its protective antioxidant defense system and push the oxidative insult to the point where, instead of enabling cancer cells to thrive, it now results in their death.
By using the supplements and repurposed medications below, we can kill cancer cells by sensitizing tumors to oxidative stress, inducing cytotoxic levels of oxidative stress, dually inhibiting the glutathione and thioredoxin systems, arresting the cancer cell cycle, and improving the immune response. We also impair glucose, glutamine, and fatty acid metabolism of tumors, as well as protective autophagy, all while keeping the “pill burden” relatively low.

• 2-deoxy-D-glucose
• Artemisinin
• Auranofin
• Disulfiram
• Docosahexaenoic acid
• Mebendazole
• Propranolol
• Sodium selenite

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida
USA

For More Information:
Beatty A, Singh T, Tyurina YY, Tyurin VA, Samovich S, Nicolas E, Maslar K, Zhou Y, Cai KQ, Tan Y, Doll S, Conrad M, Subramanian A, Bayır H, Kagan VE, Rennefahrt U, Peterson JR. Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1. Nat Commun. 2021 Apr 14;12(1):2244.
Brohée L, Peulen O, Nusgens B, Castronovo V, Thiry M, Colige AC, Deroanne CF. Propranolol sensitizes prostate cancer cells to glucose metabolism inhibition and prevents cancer progression. Sci Rep. 2018 May 4;8(1):7050.
Brüning A, Kast RE. Oxidizing to death: disulfiram for cancer cell killing. Cell Cycle. 2014;13(10):1513-4.
Guerini AE, Triggiani L, Maddalo M, Bonù ML, Frassine F, Baiguini A, Alghisi A, Tomasini D, Borghetti P, Pasinetti N, Bresciani R, Magrini SM, Buglione M. Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature. Cancers (Basel). 2019 Aug 31;11(9):1284.
Kieliszek M, Lipinski B, Błażejak S. Application of Sodium Selenite in the Prevention and Treatment of Cancers. Cells. 2017 Oct 24;6(4):39.
Onodera T, Momose I, Kawada M. Potential Anticancer Activity of Auranofin. Chem Pharm Bull (Tokyo). 2019;67(3):186-191.
Shutt DC, O'Dorisio MS, Aykin-Burns N, Spitz DR. 2-deoxy-D-glucose induces oxidative stress and cell killing in human neuroblastoma cells. Cancer Biol Ther. 2010;9(11):853-861.
Waseem Y, Hasan CA, Ahmed F. Artemisinin: A Promising Adjunct for Cancer Therapy. Cureus. 2018 Nov 23;10(11):e3628.
Zhao J, Zhou R, Hui K, et al. Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells. Oncotarget. 2017;8(12):18832-18847.

Notice:
This information for educational purposes only. It is not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your personal physician. Therefore, Dr. Thomas cannot give dosages for the above-mentioned medications. That is for your personal physician to determine after studying the references shown above.

Pages: [1] 2 3 4

© 2021 Smart + Strong. All Rights Reserved.   terms of use and your privacy
Smart + Strong® is a registered trademark of CDM Publishing, LLC.