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Cancer Research News & Studies / The Problem Of Cancer Recurrence

« Last post by danialthomas on April 09, 2021, 04:56:35 pm »

Cancer is a shrewd and highly adaptable disease. It has been outsmarting physicians for an awfully long time. With conventional treatment (chemotherapy, radiation, surgery, targeted therapy, and immunotherapy), the statistics are not good. Of the nearly 2 million people newly diagnosed with cancer last year, over 600,000 of them have already died.
Although treatment outcomes have improved with conventional treatment over the last few decades, there are significant challenges that must be overcome, such as multi-drug resistance, disease progression, metastasis, and seemingly inevitable recurrence. The need for new treatment approaches has never been more urgent.
Why does late-stage cancer recur after complete remission is achieved and there is no evidence of disease? Two big reasons for this are cancer stem cells and senescent cancer cells. If these two cell populations are not dealt with, long-term survival will be difficult to achieve.

Cancer Stem Cells:

In the human body, there are healthy stem cells that help repair and regenerate damaged tissues. Similarly, in tumors, there are cancer stem cells (CSCs) that help repair and regenerate tumors. This subset of cancer cells is also known as tumor-survival cells (TSCs) or tumor-initiating cells (TICs). Cancer stem cells are drug-resistant and remain after each round of chemotherapy to repopulate the tumor with new cancer cells.
Many experts believe that successful eradication of cancer stem cells could change the face of cancer treatment. Not only are cancer stem cells a chief driver of treatment failure, cancer progression, metastasis, and recurrence (often more aggressive), but cancer stem cells may also be the root cause of the original tumor itself. Because of the powerful survival mechanisms of cancer stem cells, chemotherapy, radiation, and surgery are unable to kill them. In fact, conventional therapy may do the opposite and stimulate the proliferation and virulence of cancer stem cells.
Cancer stem cells can migrate and nest in distant sites of the body and remain quiescent (dormant) for months, years, or even decades until the right stimuli come along and awaken them. Conventional therapy can shrink tumors; however, it will not prevent tumor recurrence. Sooner or later, lingering cancer stem cells can form new and often more aggressive tumors from a small number of cells (as few as 100). In other words, being “tumor-free” is not the same as being “cancer-free.” Eradicating tumors is not enough. Cancer stem cells must also be eradicated to achieve long-term survival.
At present, there are no drugs that are FDA-approved to specifically target cancer stem cells; however, the following supplements and repurposed medications have been found to target cancer stem cells by killing them and/or preventing them from entering a dormant and more resistant state:

• Bergamot
• Curcumin
• Doxycycline + azithromycin + vitamin C
• EGCG
• Genistein
• Resveratrol
• Sulforaphane
• Tadalafil

Senescent Cancer Cells:

Besides cancer stem cells, the other problematic cells are senescent cancer cells. Not all cancer cells can be forced into apoptosis (programmed cell death) when treated with chemotherapy, radiation, and hormone-blockers. Instead of dying, many cancer cells simply stop dividing and multiplying 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 proinflammatory molecules, protein-degrading compounds, and cancer-promoting growth factors that increase the risk of cancer recurrence.
Again, it is good that senescent cancer cells do not divide and multiply like regular cancer cells, however, in the long run, it is bad because senescent cancer cells do not die and secrete toxic compounds. Furthermore, it has been found that these compounds can stimulate cancer stem cells and promote the adverse effects of chemotherapy. If too many senescent cancer cells accumulate, recurrence of cancer can recur.
At present, there are no drugs that are FDA-approved to specifically target senescent cancer cells; however, the following supplements and repurposed medications have been found to eradicate senescent cells or decrease the toxic secretions of those senescent cells that cannot be eradicated:

• Apigenin
• Dasatinib + quercetin
• Fisetin
• FOXO4-DRI
• Melatonin
• Rapamycin
• Tocotrienols

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 for the above-mentioned supplements and medications. That is for your personal physician to determine after studying the references shown below.

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

References:

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.
Castro-Vega LJ, Jouravleva K, Ortiz-Montero P, Liu WY, Galeano JL, Romero M, Popova T, Bacchetti S, Vernot JP, Londoño-Vallejo A. The senescent microenvironment promotes the emergence of heterogeneous cancer stem-like cells. Carcinogenesis. 2015 Oct;36(10):1180-92.
De Francesco EM, Sotgia F, Lisanti MP. Cancer stem cells (CSCs): metabolic strat¬egies for their identification and eradication. Biochem J. 2018;475(9):1611-1634.
Demaria M, O'Leary MN, Chang J, Shao L, Liu S, Alimirah F, Koenig K, Le C, Mitin N, Deal AM, Alston S, Academia EC, Kilmarx S, Valdovinos A, Wang B, de Bruin A, Kennedy BK, Melov S, Zhou D, Sharpless NE, Muss H, Campisi J. Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse. Cancer Discov. 2017 Feb;7(2):165-176.
Dou Z, Berger SL. Senescence Elicits Stemness: A Surprising Mechanism for Cancer Relapse. Cell Metab. 2018 Apr 3;27(4):710-711.
Fiorillo M, Peiris-Pagès M, Sanchez-Alvarez R, Bartella L, Di Donna L, Dolce V, Sindona G, Sotgia F, Cappello AR, Lisanti MP. Bergamot natural products eradi-cate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism. Biochim Biophys Acta Bioenerg. 2018 Sep;1859(9):984-996.
Fiorillo M, Tóth F, Sotgia F, Lisanti MP. Doxycycline, Azithromycin and Vitamin C (DAV): A potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs). Aging (Albany NY). 2019 Apr 19;11(

:2202-2216.
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.
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.
Klutzny, S., Anurin, A., Nicke, B. et al. PDE5 inhibition eliminates cancer stem cells via induction of PKA signaling. Cell Death Dis 9, 192 (2018).
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.
Naujokat C, McKee DL. The “Big Five” Phytochemicals Targeting Cancer Stem Cells: Curcumin, EGCG, Sulforaphane, Resveratrol and Genistein. Curr Med Chem. 2020 Feb 27.
Pernicová Z, Slabáková E, Kharaishvili G, et al. Androgen depletion induces senescence in prostate cancer cells through down-regulation of Skp2. Neoplasia. 2011;13(6):526-536.
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.
Selli C, Turnbull AK, Pearce DA, Li A, Fernando A, Wills J, Renshaw L, Thomas JS, Dixon JM, Sims AH. Molecular changes during extended neoadjuvant letrozole treatment of breast cancer: distinguishing acquired resistance from dormant tumours. Breast Cancer Res. 2019 Jan 7;21(1):2.
Tabasso AFS, Jones DJL, Jones GDD, Macip S. Radiotherapy-Induced Senescence and its Effects on Responses to Treatment. Clin Oncol (R Coll Radiol). 2019 May;31(5):283-289.
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.
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).
Zhu M, Meng P, Ling X, Zhou L. Advancements in therapeutic drugs targeting of senescence. Ther Adv Chronic Dis. 2020 Oct 13;11:2040622320964125

Cancer Research News & Studies / My Personal Wellness Plan

« Last post by danialthomas on March 28, 2021, 09:16:56 am »

I view life is a precious gift and our health as our greatest asset. I take this very seriously, especially since I have patients whose lives depend on me. They cannot afford for me to fall ill. I reject the belief that chronic disease is an inevitable result of aging. Below are the five things that I do to maintain the highest degree of physical health and mental vigor, and resist the “diseases of aging,” including cancer, heart attack, stroke, hypertension, obesity, type 2 diabetes, osteoarthritis, osteoporosis, frequent infections, autoimmunity, cataracts, macular degeneration, depression, dementia, Parkinson’s disease, chronic fatigue, and sarcopenia (frailty):

1. Cultivate A Healthy Lifestyle:
• Eat an organic, whole-food, plant-based diet and reduce portion sizes
• Don’t smoke or drink
• Drink plenty of water
• Weight: Keep within 5% of optimal
• Blood pressure: Keep under 120/80
• Get sound sleep
• Engage in strength-training exercise 3-4 days per week
• Spend time outdoors
• Manage stress

2. Maintain Optimal Bloodwork:
• Cholesterol: 160-180 mg/dL
• LDL: <100 mg/dL
• HDL: >60 mg/dL
• Triglycerides: <100 mg/dL
• Cortisol (stress hormone): <13 ug/dL
• Fibrinogen (blood clot potential): <276 mg/dL
• hs-CRP (silent inflammation): <0.6 mg/L
• Homocysteine (methylation): <7.1 μmol/L
• Fasting glucose: 60-80 mg/dL
• Fasting insulin: <6 uIU/mL
• GlycoMark® (absence of post-mealtime glucose spiking): >19 mg/mL
• Hemoglobin A1c (average glucose level for the last 90 days): <5.3%
• Ferritin (iron): Women: 20-30 ng/mL; Men: 40-50 ng/mL
• Vitamin D: 40-60 ng/mL

3. Remove Senescent Cells And Inhibit Their Toxic Secretions:
Cellular senescence is an age-related process in which old cells lose the ability to divide and create new cells. This process is one of the main causes of the physical signs of aging and manifests in various diseases, such as arthritis, osteoporosis, heart disease, cancer, diabetes, frailty, and dementia. Senescent cells accumulate over time and secrete pro-inflammatory and protein-degrading compounds that damage neighboring healthy cells and accelerate the aging process. Many scientists believe that by eradicating as many senescent cells as possible and suppressing the secretion of the harmful compounds of the remaining senescent cells, we could lead a more disease-free life, bring back a more youthful vigor, and extend lifespan. To remove senescent cells, I take a “senolytic” cocktail consisting of prescription dasatinib along with bioavailable quercetin and fisetin. To inhibit the toxic secretions of the remaining senescent cells, I take a “senomorphic” cocktail of prescription rapamycin along with tocotrienols and bioavailable apigenin.

4. Boost AMPK Activity And Reduce Excess mTOR Signaling:
AMPK (adenosine monophosphate-activated protein kinase) 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. Activating AMPK can reduce the risk of heart attack, stroke, hypertension, obesity, diabetes, osteoporosis, cancer, and Alzheimer’s disease. When mTOR (mechanistic target of rapamycin) is constantly elevated, it increases the risk of degenerative diseases. Many of the health benefits of fasting (calorie restriction) emanate from increased AMPK activity and reduced mTOR signaling and the resultant upregulation of autophagy (removal of toxic cellular waste). I fast for 16 hours a day, limit my window period of eating to 6 hours, and eat two meals per day instead of three. In addition, to amplify the benefits of fasting, I take a calorie-restriction-mimetic cocktail of hydroxycitrate, bioavailable resveratrol and luteolin, piperlongumine, spermidine, and white willow bark.

5. Resetting 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. As such, I take GHK as a subcutaneous microinjection.

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 determine appropriateness of use for your situation regarding the above-mentioned supplements and medications. That is for your personal physician to decide.

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

Cancer Research News & Studies / Cancer Cachexia

« Last post by danialthomas on March 18, 2021, 05:29:45 pm »

Cancer cachexia (pronounced kuh-KEK-see-uh) is a complex metabolic wasting syndrome caused by cancer. It is a devastating and debilitating condition encountered in more than half of late-stage cancer patients. It is characterized by marked weight loss due to a dramatic loss of muscle and body fat. It is accompanied by a lack of appetite, fatigue, decreased strength, and depression. Patients can become so frail and weak that just walking can be difficult.

Cachexia compromises the effectiveness of cancer treatment, is a strong predictor of poor prognosis and accounts for nearly one-third of all cancer deaths. Sadly, no safe and effective conventional treatment exists. Because of this urgent and unmet medical need in cancer treatment, here is what I use to counteract cancer cachexia and help rescue patients from its devastating consequences:

• Altered taste: If food does not taste normal (side effect of chemotherapy), consider taking Miracle Fruit.
• Appetite stimulant: If appetite is poor, consider asking your doctor to pre-scribe megestrol acetate (Megace®) oral suspension.
• Extra calories: If appetite is good but you need extra calories, consider adding 2-3 plant-based, high-calorie protein smoothies daily.
• Nausea: If nausea is preventing a good appetite, consider the use of taurine along with ginger/peppermint tea.
• Systemic inflammation: A major driver of cancer cachexia. If your levels of high-sensitivity C-reactive protein, homocysteine, and/or fibrinogen activity are elevated, there are natural compounds that can help lower them.
• Creatine: Combats muscle wasting.
• Exercise: Combats muscle wasting.
• Imperatorin: Active component of the herb Angelica dahurica. Combats muscle wasting.
• Omega-3 fatty acids: Combats muscle wasting.
• Autophagy inhibition: Autophagy of the tumor is a major contributor to cancer cachexia. Consider the use of over-the-counter loratadine and black seed oil, or prescription hydroxychloroquine and dipyridamole.
• BPC157: This is a medicinal peptide that combats muscle wasting.
• Follistatin: This also is a medicinal peptide that combats muscle wasting.
• Oxytocin: This too is a medicinal peptide that combats muscle wasting.

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 for the above-mentioned supplements and medications. That is for your personal physician to determine.

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

References:

Benoni A, Renzini A, Cavioli G, Adamo S. Neurohypophyseal hormones and skeletal muscle: a tale of two faces. Eur J Transl Myol. 2020;30(1):8899.
Cole CL, Kleckner IR, Jatoi A, Schwarz EM, Dunne RF. The Role of Systemic Inflammation in Cancer-Associated Muscle Wasting and Rationale for Exercise as a Therapeutic Intervention. JCSM Clin Rep. 2018;3(2):e00065.
de Matos-Neto EM, Lima JD, de Pereira WO, Figuerêdo RG, Riccardi DM, Radloff K, das Neves RX, Camargo RG, Maximiano LF, Tokeshi F, Otoch JP, Goldszmid R, Câmara NO, Trinchieri G, de Alcântara PS, Seelaender M. Systemic Inflammation in Cachexia - Is Tumor Cytokine Expression Profile the Culprit? Front Immunol. 2015 Dec 24;6:629.
Kang EA, Han YM, An JM, Park YJ, Sikiric P, Kim DH, Kwon KA, Kim YJ, Yang D, Tchah H, Hahm KB. BPC157 as Potential Agent Rescuing from Cancer Cachexia. Curr Pharm Des. 2018;24(18):1947-1956.
Linlin Chen, Weiheng Xu, Quanjun Yang, Hong Zhang, Lili Wan, Bo Xin, Junping Zhang, Cheng Guo. Imperatorin alleviates cancer cachexia and prevents muscle wasting via directly inhibiting STAT3. Pharmacological Research. Volume 158, 2020, 104871, ISSN 1043-6618.
Loumaye A, de Barsy M, Nachit M, Lause P, Frateur L, van Maanen A, Trefois P, Gruson D, Thissen JP. Role of Activin A and myostatin in human cancer cachexia. J Clin Endocrinol Metab. 2015 May;100(5):2030-8.
Loumaye A, de Barsy M, Nachit M, Lause P, van Maanen A, Trefois P, Gruson D, Thissen JP. Circulating Activin A predicts survival in cancer patients. J Cachexia Sarcopenia Muscle. 2017 Oct;8(5):768-777.
Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, et al. The autophagic tumor stroma model of cancer or “battery-operated tumor growth”: A simple solution to the autophagy paradox. Cell Cycle. 2010;9(21):4297-4306.
Murphy RA, Mourtzakis M, Mazurak VC. n-3 polyunsaturated fatty acids: the potential role for supplementation in cancer. Current opinion in clinical nutrition and metabolic care. May 2012;15(3):246-251.
Padilha, Camila Souza, Cella, Paola Sanches, Salles, Leo Rodrigues, & Deminice, Rafael. (2017). Oral creatine supplementation attenuates muscle loss caused by limb immobilization: a systematic review. Fisioterapia em Movimento, 30(4), 831-838.
Rautela J, Dagley LF, de Oliveira CC, Schuster IS, Hediyeh-Zadeh S, Delconte RB, Cursons J, Hennessy R, Hutchinson DS, Harrison C, Kita B, Vivier E, Webb AI, Degli-Esposti MA, Davis MJ, Huntington ND, Souza-Fonseca-Guimaraes F. Therapeutic blockade of activin-A improves NK cell function and antitumor immunity. Sci Signal. 2019 Aug 27;12(596):eaat7527.
Wilken MK, Satiroff BA. Pilot study of “miracle fruit” to improve food palatability for patients receiving chemotherapy. Clin J Oncol Nurs. 2012 Oct;16(5):E173-7.

Cancer Research News & Studies / Why do so few people benefit from “breakthrough” cancer immunotherapy?

« Last post by danialthomas on March 13, 2021, 05:07:06 pm »

When the first immunotherapy drug ipilimumab (Yervoy) was FDA approved in 2011, immunotherapy was hailed as breakthrough in cancer treatment. This new therapy harnessed the power of the body’s own immune system to fight cancer. Fast forward to today and, unfortunately, only a minority of cancer patients actually benefit from immunotherapy in terms of tumor shrinkage, and even fewer experience long-term survival.
Why did immunotherapy not live up to the hype? It turns out that simply “revving up” the immune system is not enough. Having plenty of natural-killer (NK) cells, cytotoxic T-cells (CTCs), and M1 macrophages is insufficient. Tumors still have ways to avoid immune destruction which include:

• Recruitment of immunosuppressive T-regulatory cells (Tregs) and myeloid cells.
• Recruitment of tumor-killing M1 macrophages and polarizing them into tumor-promoting M2 macrophages (also known as tumor-associated macrophages or TAMs).
• Malignant cell exposure to blood platelets.
• Iron-induced parafibrin formation blocking immune-mediated destruction.
• Tumor collagen density preventing adequate infiltration of immune cells.
• Lack of sufficient energy by immune cells.
To improve the efficacy of immunotherapy, it is important to:
• Reduce Tregs and myeloid cells using ivermectin.
• Repolarize tumor-promoting M2 macrophages into tumor-killing M1 macrophages using onionin A, a sulfur-containing compound from onions.
• Reduce platelet aggregation and reduce tumor density using pentoxifylline (Trental).
• Block formation of parafibrin using curcumin, EGCG, ferulic acid, magnesium, and sodium selenite.
• Supplement with creatine. Creatine, a supplement that is popular with athletes and bodybuilders, serves as a “molecular battery” for immune cells by storing and distributing energy to power their fight against cancer.

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 for the above-mentioned supplements and medications. That is for your personal physician to determine.

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

References:
Bałan BJ, Demkow U, Skopiński P, et al. The effect of pentoxifylline on L-1 sarcoma tumor growth and angiogenesis in Balb/c mice. Cent Eur J Immunol. 2017;42(2):131-139.
Draganov D, Han Z, Rana A, Bennett N, Irvine DJ, Lee PP. Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for treatment of breast cancer. NPJ Breast Cancer. 2021 Mar 2;7(1):22.
Kim JH, Shin BC, Park WS, Lee J, Kuh HJ. Antifibrotic effects of pentoxifylline improve the efficacy of gemcitabine in human pancreatic tumor xenografts. Cancer Sci. 2017 Dec;108(12):2470-2477.
Lipinski B. Iron-induced parafibrin formation in tumors fosters immune evasion.
Stefano Di Biase, Xiaoya Ma, Xi Wang, Jiaji Yu, Yu-Chen Wang, Drake J. Smith, Yang Zhou, Zhe Li, Yu Jeong Kim, Nicole Clarke, Angela To, Lili Yang; Creatine uptake regulates CD8 T cell antitumor immunity. J Exp Med 2 December 2019; 216 (12): 2869–2882.
Tsuboki, J., Fujiwara, Y., Horlad, H. et al. Onionin A inhibits ovarian cancer pro-gression by suppressing cancer cell proliferation and the protumour function of macrophages. Sci Rep 6, 29588 (2016).

Cancer Research News & Studies / Besides IV Vitamin C

« Last post by danialthomas on March 06, 2021, 03:55:21 pm »

People often ask me, “Besides IV vitamin C, what other types of alternative IV’s are being used to treat cancer?” A pro-oxidative compound that may be more potent than intravenous vitamin C is intravenous sodium selenite, augmented with intravenous ozone and oral nicotinamide, pentoxifylline, and sulindac. This must be administered through a chest port and not an arm vein.

On another front, there are two medicinal plant compounds that look extremely promising. Found in eggplant, they are called solamargine and solasonine. Based on scientific research, these compounds appear to have the following characteristics:

• 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 retail or compounding pharmacies. Because of this, we are having medicinal chemists custom synthesize these compounds and purify them to pharmaceutical levels. To assure full absorption and prevent possible chemical alteration by stomach acids and gut bacteria from oral administration, solamargine and solasonine will be administered intravenously.

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

Cancer Research News & Studies / Top 10 Questions To Ask Your Oncologist

« Last post by danialthomas on December 31, 2020, 03:25:33 pm »

Cancer is a serious and terrifying disease. If you have been diagnosed with cancer, your mind is probably filled with fear, worry, and questions. Therefore, it is extremely important to have an honest and frank discussion with your oncologist. To better understand your disease and treatment options, it is imperative to ask the right questions. If you are determined to beat cancer, here are the top 10 questions you need to ask your oncologist:
1. What is the rationale for your recommended treatment and is your expectation curative (achieving remission and long-term survival) or palliative (only improving quality of life)?
2. What are the likely side effects of treatment and how will you deal with each of them?
3. How do you plan to prevent damage to the DNA and mitochondria of my normal (healthy) cells?
4. How many of the eleven hallmarks of cancer will you be targeting (see www.thomashealthblog.com/?p=11249?)
5. Treatment resistance, systemic toxicity, and immunosuppression are leading causes of treatment failure and subsequent mortality. What is your plan to overcome these challenges if they occur?
6. Every drug that is used to treat malignancies must reach the cancer cells in the tumor environment at adequate concentrations to exert their intended cell-killing effects. Two obstacles that exist in the tumor environment that can prevent adequate delivery of cancer-killing substances are tumor interstitial hypertension and tumor density. What will you be doing to overcome these obstacles?
7. Studies have shown that a significant percentage of cancer cases have their roots in diet and lifestyle. Also, chemotherapy and radiation can lead to nutritional deficiencies. To address these issues, what diet, lifestyle, and nutritional supplements do you recommend that may improve my treatment outcome?
8. Cancer cells alter their metabolism to enable rapid growth and proliferation and enable treatment resistance. Targeting cancer metabolism as a therapeutic strategy can support conventional therapy. To improve my treatment response, what will you be doing to target cancer metabolism?
9. Cancer stem cells are thought to be a major cause of treatment failure, cancer progression, metastasis, and cancer recurrence. What will you be doing to target cancer stem cells since chemotherapy, radiation, and surgery do not target these cells and may stimulate them to proliferate and spread?
10. The tumor stroma (non-cancer cells in a tumor) has been shown to promote cancer initiation, progression, metastasis, and treatment resistance. Conventional cancer treatment is designed to target cancer cells. What will you be doing to simultaneously target the tumor stroma cells, such as cancer-associated fibroblasts and tumor-associated macrophages?
The above questions will help you prepare for your appointment so you will come away from the visit with the crucial information you need to move forward and fight cancer properly. Do not be afraid to ask these questions. Your health and very life may be on the line, so insist on complete answers from your oncologist. Ask a friend or family member to accompany you as a second set of eyes and ears to listen to what the doctor says. And be sure to take notes for later reference.
It is important to have your eyes wide open as you move forward, so please be aware that the oncologist may not be current in his or her understanding of cancer cell biology, how to lessen metastatic progression and improve therapeutic response using integrative therapies, or how to prevent disease recurrence. The oncologist may not be informed about the role that nutrition plays in fighting cancer and may mock the idea of doing anything to target cancer hallmarks (including cancer metabolism), cancer stem cells, the tumor stroma, or improving drug delivery to tumors, and might be dismissive of anything outside of conventional therapy. Therefore, I urge to you also consult with a physician who possesses a deeper understanding of the complex biology of cancer and is educated and experienced in integrative therapies. Please do not contact my office as my practice is full and I am unable to see new patients. Instead, to locate a physician, please visit www.bestanswerforcancer.org/find-a-physician.

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

Cancer Research News & Studies / New Year’s Resolution For 2021

« Last post by danialthomas on December 25, 2020, 04:35:34 pm »

As a metabolic physician with 33 years of experience treating advanced-stage cancer, and as a translational researcher spending 20-30 hours a week sifting through the scientific literature in search of potentially promising treatments, my New Year’s resolution for 2021 is to continue to provide my patients with innovative and powerful weapons to fight cancer, but now to look for new ways to use fewer and fewer supplements and repurposed medications, while still eradicating cancer cells and cancer stem cells, improving immune rejection of cancer, modulating the tumor microenvironment to improve penetration and delivery of anti-cancer compounds, and preventing cancer recurrence. I will post information from time to time so that you may share it with your oncologist and/or integrative doctor.

Happy New Year!
Dr. Daniel Thomas, DO, MS
Mount Dora, Florida USA

Cancer Research News & Studies / Finding A Doctor

« Last post by danialthomas on December 18, 2020, 03:21:48 pm »

To locate a DO or MD that may be able to help you take an integrative and metabolic approach to cancer, I recommend using these physician directories:

1. Academy of Comprehensive Integrative Medicine: www.acimconnect.com/Resources/Find-a-Health-Professional
2. American Academy of Anti-Aging Medicine: www.a4m.com/find-a-doctor.html
3. American College for Advancement in Medicine: www.acam.org/search/custom.asp?id=1758
4. Best Answer for Cancer Foundation: www.bestanswerforcancer.org/find-a-physician
5. Functional Medicine Institute: www.ifm.org/find-a-practitioner
6. Society for Integrative Oncology: www.integrativeonc.org/public-directory

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

Cancer Research News & Studies / Update: Hallmarks Of Cancer

« Last post by danialthomas on December 09, 2020, 04:01:30 pm »

Recently, I wrote about the hallmarks of cancer. Tumors are well organized structures, and they follow a strict set of rules. Scientists have identified universal pillars or traits of human malignancy that allow it to grow and spread. Collectively, these are called the “hallmarks” of cancer, and therapeutically targeting them as many as possible can enhance conventional treatment and improve your chances for achieving remission and long-term survival.
On December 3, 2020, an article entitled “Targeting the pH Paradigm at the Bedside: A Practical Approach” was published in the International Journal of Molecular Sciences. The author of the article provided compelling evidence that we should expand the list of hallmarks of cancer from ten to eleven (see below). What is important about #11 on the list, is that the reversal of pH is not dependent on lactic acid production from the Warburg effect and takes place before the Warburg effect is functionally operative. Furthermore, lactic acid is not the only cause of acidity, as carbon dioxide is equally important.

1. Resistance to apoptosis (cell death): Apoptosis is a protective mechanism by which cells are programmed to die if they become damaged and potentially harmful. Cancer cells bypass this mechanism. Therapeutic target: Activate caspase protease enzymes and downregulate TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) protein.

2. Replicative immortality: Normal cells die after a finite number of cell divisions. Cancer cells bypass this limit and are capable of infinite divisions (immortality) and sustained proliferation. Therapeutic target: Deactivate telomerase and destabilize telomeres.

3. Evading immune attack: Cytotoxic T-cells (CTCs) and natural killer (NK) cells are the main anti-cancer immune cells. CTCs and NK cells can be rendered impotent by immunosuppressive cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and T-regulatory cells (Tregs) in the tumor microenvironment. Therapeutic targets: Increase the number and competency of CTCs and NK cells, reprogram CAFs and TAMs, and suppress the activity of Tregs.

4. Genetic instability: DNA is damaged thousands of times during each cell division. That damage must be repaired, including in cancer cells. Otherwise, the cells may die due to this damage. Therapeutic target: Inhibit the enzyme known as PARP (poly ADP-ribose polymerase) used by cells to repair damage to their DNA.

5. Altered metabolism and deregulated cellular energetics: The metabolism of cancer cells and the tumor stroma is different from normal cells. Cancer and stromal cells use alternative metabolic pathways to generate energy and building blocks to fuel malignant growth and spread. Therapeutic targets: Disable metabolic coupling between cancer cells and stromal cells and deprive cancer of the high-energy nutrients it needs (i.e., glucose, glutamine, fatty acids, ketones, and lactate).

6. Inflammation: Local or systemic inflammation induced by the tumor microenvironment acts as a major driver of cancer. Therapeutic target: Suppress local and systemic inflammation.

7. Tumor hypoxia and angiogenesis: A growing tumor soon outstrips its oxygen and blood supply and needs to grow new blood vessels to deliver oxygen and nutrients. To orchestrate this, cancer cells boost the production of growth factors that stimulate angiogenesis. Therapeutic target: Inhibit hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF).

8. Invasion and metastasis: Cancer cells invade surrounding tissue and spread (metastasize) to distant sites in the body. Therapeutic targets: Inhibit HGF (hepatocyte growth factor), c-Met (mesenchymal-epithelial transition factor), lymphangiogenesis (growth of new lymph vessels), and exosome release.

9. Sustained proliferative signaling: Cancer cells can permanently activate signaling pathways that promote excessive growth. It’s like the accelerator pedal is stuck. Therapeutic targets: Inhibit cancer-promoting MDM2 oncogene and block epidermal growth factor receptor (EGFR).

10. Evading growth suppressors: To prevent overcrowding, normal cells have mechanisms that prevent excess cell growth and division. In cancer cells, tumor suppressor proteins are altered so they don’t prevent cell division. It’s like the brakes don’t work. Therapeutic targets: Unmutate and activate the cancer-suppressor p53 gene and inhibit cyclin-dependent kinases (CDKs).

11. Reversal of the pH gradient: In normal cells, the intracellular environment is more acidic (lower pH), and the extracellular environment is more alkaline (higher pH). In cancer cells, this is reversed, where the intracellular environment is more alkaline, and the extracellular environment is more acidic. This condition enables tumors to grow and spread, resist the effects of chemotherapy, and inhibit immune attack. Therapeutic targets: Decrease the pH of the intracellular environment of cancer cells and increase the pH of the extracellular environment by inhibiting membrane carbonic anhydrases and monocarboxylate transporters.

If you or a loved one are being treated for cancer, to improve your/their chances of beating the disease, be sure to ask the oncologist how many of the above hallmarks of cancer he/she is targeting. If it is not all eleven hallmarks, to address any that are being ignored, I urge to you seek the services of a physician who possesses a deep understanding of the complex biology of cancer and is educated and experienced in integrative therapies. (Please do not contact my office as my practice is full and I am unable to accept new patients.)

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

Living with Breast Cancer / Re: diagnosed with triple negative BC

« Last post by katiem on December 04, 2020, 01:34:45 pm »

Thank you!

I will check these out

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