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Cancer Research News & Studies / Novel Cancer Approach Discovered By Scientists

« Last post by danialthomas on October 19, 2021, 04:53:36 pm »

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.

Cancer Research News & Studies / Lithium

« Last post by danialthomas 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.

Cancer Research News & Studies / Targeting Tumor Hypoxia

« Last post by danialthomas 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(

: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

Cancer Research News & Studies / The Origins Of Cancer

« Last post by danialthomas 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(

: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.

Cancer Research News & Studies / Ferroptosis in Cancer Treatment: More Than One Way to Skin a Cat

« Last post by danialthomas on September 12, 2021, 04:57:41 pm »

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.

Cancer Research News & Studies / How To Reduce Pill-Burden When Treating Cancer

« Last post by danialthomas on September 07, 2021, 04:07:01 pm »

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.

Cancer Research News & Studies / Iron Removal Enhances Intravenous Vitamin C-Induced Apoptosis Of Cancer Cells

« Last post by danialthomas on August 31, 2021, 06:46:03 pm »

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

Cancer Research News & Studies / Is There Such A Thing As Stage 1 Or Stage 2 Cancer

« Last post by danialthomas on August 25, 2021, 03:25:13 pm »

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.

Cancer Research News & Studies / Staying Healthy After Cancer

« Last post by danialthomas 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:
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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.
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Cancer Research News & Studies / Covid 19

« Last post by danialthomas 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

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