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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.

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1
Cancer Research News & Studies / Overcoming Problems Of Chemotherapy
« Last post by danialthomas on May 15, 2022, 06:09:57 pm »
Cytotoxic chemotherapy remains a primary treatment option to fight cancer. There are three main problems with chemotherapy that must be dealt with if you intend to beat cancer and maintain a decent quality of life:

1. Drug resistance: In metastatic cancer, chemotherapy is rarely curative. Drug resistance limits its therapeutic effectiveness. Resistance can be either pre-existent (intrinsic resistance) or induced by drugs (acquired resistance).

2. Cancer stem cells: These are a small subpopulation of resting cancer cells within a tumor. Cancer stem cells are a leading cause of metastasis and cancer recurrence. Most standard chemotherapy drugs are designed to target rapidly dividing cells. Due to their low proliferation rate, chemotherapy preferentially spares cancer stem cells. Not only does chemotherapy fail to target cancer stem cells, it can do the exact opposite and stimulate them to proliferate and spread.

3. Side effects: Most standard chemotherapies kill cells by a process known as indiscriminate cytotoxicity. Consequently, standard- or full-dose chemotherapy is indiscriminate and has a low safety profile. There will likely be collateral damage. Chem­otherapy drugs not only target rapidly dividing cancer cells, but due to their sys­temic toxicity, normal cells will also be affected. This can cause serious side effects, including damage to the heart, lungs, liver, kidneys, and nervous system.
The solution to circumventing drug resistance is to chemosensitize cancer cells. This makes them more vulnerable to the cytotoxic effects chemotherapy. It may also lessen the dose of chemotherapy needed to induce apoptosis (death) of cancer cells which, in turn, can lessen the side effects. Natural compounds that have been found to be chemosensitizers include berberine, curcumin, EGCG, quercetin, resveratrol, solamargine, sulforaphane, and high-dose intravenous vitamin C. Medications include 2-deoxy-D-glucose, artesunate, fenofibrate, itraconazole, ivermectin, and pentoxifylline.
There are no drugs yet that are FDA-approved to target cancer stem cells. To address this urgent and unmet need, the following natural compounds and pre­scrip­tion medication should be considered, as they 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, EGCG, genistein, resveratrol, sodium selenite, sul­foraphane, tadalafil, and intravenous vitamin C with low-dose azithromycin and doxycycline.
To help protect yourself during chemotherapy, if your oncologist will not agree to administering low-dose chemotherapy, chemoprotectants should be considered. These are compounds that can reduce the toxic effects of chemotherapy without com­pro­mising the anti­cancer effects. The natural products and pre­scription medica­tions that can reduce the damage from chemotherapy include ashwagandha, berberine, bitter melon, curcumin, lycopene, melatonin, resveratrol, and pentoxifylline.

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

References:

Aghaee F, Pirayesh Islamian J, Baradaran B. Enhanced radiosensitivity and chemosensitivity of breast cancer cells by 2-deoxy-D-glucose in combination therapy. J Breast Cancer. 2012 Jun;15(2):141-7.
Barancik M, Bohacova V, Gibalova L, Sedlak J, Sulova Z, Breier A. Potentiation of anticancer drugs: effects of pentoxifylline on neoplastic cells. Int J Mol Sci. 2012;13(1):369-382.
Cham, B. (2017) Solasodine, Solamargine and Mixtures of Solasodine Rhamnosides: Pathway to Expansive Clinical Anticancer Therapies. International Journal of Clinical Medicine, 8, 692-713.
Cham, B. Combination Treatment with BEC and Cisplatin Synergistically Augments Anticancer Activity and Results in Increased Absolute Survival. Journal of Cancer Therapy, Vol.11 No.8, 2020.
Chen W, An J, Guo J, Wu Y, Yang L, Dai J, Gong K, Miao S, Xi S, Du J. Sodium selenite attenuates lung adenocarcinoma progression by repressing SOX2-mediated stemness. Cancer Chemother Pharmacol. 2018 May;81(5):885-895.
De Francesco EM, Sotgia F, Lisanti MP. Cancer stem cells (CSCs): metabolic strat­egies for their identification and eradication. Biochem J. 2018;475(9):1611-1634.
Devarajan N, Jayaraman S, Mahendra J, Venkatratnam P, Rajagopal P, Palaniappan H, Ganesan SK. Berberine-A potent chemosensitizer and chemoprotector to conventional cancer therapies. Phytother Res. 2021 Jun;35(6):3059-3077.
Fan LX, Liu CM, Gao AH, Zhou YB, Li J. Berberine combined with 2-deoxy-d-glucose synergistically enhances cancer cell proliferation inhibition via energy depletion and unfolded protein response disruption. Biochim Biophys Acta. 2013 Nov;1830(11):5175-83.
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 eradicate 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(8):2202-2216.
Golunski G, Woziwodzka A, Piosik J. Potential Use of Pentoxifylline in Cancer Therapy. Curr Pharm Biotechnol. 2018;19(3):206-216.
Hamed, A.R., Abdel-Azim, N.S., Shams, K.A. et al. Targeting multidrug resistance in cancer by natural chemosensitizers. Bull Natl Res Cent 43, 8 (2019).
Jiang L, Wang P, Sun YJ, Wu YJ. Ivermectin reverses the drug resistance in cancer cells through EGFR/ERK/Akt/NF-κB pathway. J Exp Clin Cancer Res. 2019 Jun 18;38(1):265.
Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A. The multitargeted drug iver­mectin: from an antiparasitic agent to a repositioned cancer drug. Am J Cancer Res. 2018;8(2):317-331.
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).
Liang CH, Liu LF, Shiu LY, Huang YS, Chang LC, Kuo KW. Action of solamargine on TNFs and cisplatin-resistant human lung cancer cells. Biochem Biophys Res Commun. 2004 Sep 24;322(3):751-8.
Li S, Liao R, Sheng X, et al. Hydrogen Gas in Cancer Treatment. Front Oncol. 2019;9:696. Published 2019 Aug 6.
Liu H, Kurtoglu M, León-Annicchiarico CL, et al. Combining 2-deoxy-D-glucose with fenofibrate leads to tumor cell death mediated by simultaneous induction of energy and ER stress. Oncotarget. 2016;7(24):36461-36473.
Ma Z, Xu L, Liu D, et al. Utilizing Melatonin to Alleviate Side Effects of Chemo­therapy: A Potentially Good Partner for Treating Cancer with Ageing. Oxid Med Cell Longev. 2020;2020:6841581.
Mohammad RM, Muqbil I, Lowe L, Yedjou C, Hsu HY, Lin LT, Siegelin MD, Fimognari C, Kumar NB, Dou QP, Yang H, Samadi AK, Russo GL, Spagnuolo C, Ray SK, Chakrabarti M, Morre JD, Coley HM, Honoki K, Fujii H, Georgakilas AG, Amedei A, Niccolai E, Amin A, Ashraf SS, Helferich WG, Yang X, Boosani CS, Guha G, Bhakta D, Ciriolo MR, Aquilano K, Chen S, Mohammed SI, Keith WN, Bilsland A, Halicka D, Nowsheen S, Azmi AS. Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol. 2015 Dec;35 Suppl(0):S78-S103.
Monu, Pushpa C. Tomar, Shilpa S. Chapadgaonkar. Natural Chemoprotectants for Mitigating the Side Effects of Cancer Therapy. Ambient Science, 2019: Vol. 06(Sp1); Online.
Naujokat C, McKee DL. The “Big Five” Phytochemicals Targeting Cancer Stem Cells: Curcumin, EGCG, Sulforaphane, Resveratrol and Genistein. Curr Med Chem. 2020 Feb 27.
Pounds R, Leonard S, Dawson C, Kehoe S. Repurposing itraconazole for the treat­ment of cancer. Oncol Lett. 2017;14(3):2587-2597.
Raimundo Gonçalves de Oliveira Júnior, Alves Ferraz Christiane Adrielly, Jackson Roberto Guedes da Silva Almeida, Raphaël Grougnet, Valérie Thiéry, Laurent Picot, Sensitization of tumor cells to chemotherapy by natural products: A system­atic review of preclinical data and molecular mechanisms, Fitoterapia, Volume 129, 2018, Pages 383-400.
Sun J, Zheng Z, Chen Q, Pan Y, Quan M, Dai Y. Fenofibrate potentiates chemosensitivity to human breast cancer cells by modulating apoptosis via AKT/NF-κB pathway. Onco Targets Ther. 2019 Jan 23;12:773-783.
Wang B, Hou D, Liu Q, Wu T, Guo H, Zhang X, Zou Y, Liu Z, Liu J, Wei J, Gong Y, Shao C. Artesunate sensitizes ovarian cancer cells to cisplatin by downregulating RAD51. Cancer Biol Ther. 2015;16(10):1548-56.
Zhang F, Aft RL. Chemosensitizing and cytotoxic effects of 2-deoxy-D-glucose on breast cancer cells. J Cancer Res Ther. 2009 Sep;5 Suppl 1:S41-3.
Zhang QY, Wang FX, Jia KK, Kong LD. Natural Product Interventions for Chem­o­therapy and Radiotherapy-Induced Side Effects. Front Pharmacol. 2018;9:1253.

Disclaimer:
This information is strictly for educational purposes only and not intended or implied to be personal medical advice. That is for your personal physician to provide after he or she accesses and reads each of the references above.
2
Cancer Research News & Studies / Cancer Cachexia
« Last post by danialthomas on May 08, 2022, 04:37:06 am »
Cancer cachexia (pronounced kuh-KEK-see-uh) is a 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 substantial 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 negatively impacts the effectiveness of cancer treatment. It 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 are recommendations 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. Recommended brand: mberry Miracle Fruit Tablets. Suggested dosage: One tablet before major meals.
· Extra calories: If appetite is good but you need extra calories, consider add­ing 2-3 plant-based, high-calorie protein smoothies daily. See https://www.planthlete.com/.../high-calorie-vegan.../
· Nausea: If nausea is preventing a good appetite, please consider Alvita Organic Ginger-Peppermint tea. Suggested amount: Drink up to 4-5 cups of tea through-out the day. Also consider the amino acid taurine. Suggested dosage: One 1000 mg capsule 3 times daily.
· Systemic inflammation: A major driver of cancer cachexia. If your levels of high-sensitivity C-reactive protein, homocysteine, and/or fibrinogen activity are elevated, besides eating a plant-based diet, consider taking Boswellia & ginger, bromelain, curcumin, nattokinase, specialized pro-resolving mediators, and trimethylglycine.
· Creatine: Combats muscle wasting. Recommend brand: Life Extension Creatine Capsules. Suggested dosage: Two capsules 2-3 times daily.
· Exercise: Combats muscle wasting. Consider the 30-Minute Express Workout 3 days per week at your local Planet Fitness gym. If you do not live near a Planet Fitness, you can do strength training at home using exercise bands. If you are una­ble to participate in strength training, a regular walking program can help.
· Imperatorin: Active component of the herb Angelica dahurica. Combats muscle wasting.Recommended brand: Hawaii Pharm Bai Zhi (Angelica Dahurica) Liquid Herbal Extract. Suggested dosage: 30 drops stirred a glass of water 4 times daily.
· Omega-3 fatty acids: Combats muscle wasting. Recommended brand: Nordic Naturals Ultimate Omega. Suggested dosage: Two capsules twice daily.
· Autophagy inhibition: Autophagy of the tumor stroma 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 custom-compounded, prescription medicinal peptide that combats muscle wasting. It is a self-administered subcutane­ous microinjec­tion. Recommended com­pounding pharmacy: Tailor Made Compounding. Suggested dosage: 250 mcg injected twice daily, 20 days in a row. Repeat every other month.
· Follistatin: This too is a custom-compounded, prescription medicinal pep­tide that combats muscle wasting. It is a self-administered subcutane­ous microinjec­tion. Recommended com­pounding pharmacy: Tailor Made Com­pounding. Suggested dosage: 200 mcg injected daily, 10 days in a row. Repeat monthly.
· Megestrol acetate (Megace®): This is an appetite stimulant. Suggested dos­age: 800 mg orally once a day (20 mL/day).
· Oxytocin: This too is a custom-compounded, prescription medicinal peptide that combats muscle wasting. It is self-administered as a troche which is a small lozenge that dissolves between the cheek and gum over a period of 20-30 minutes. Recom­mended com­pounding pharmacy: Tailor Made Com­pounding Pharmacy. Suggested dosage: 40 IUs 1-2 times daily.


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.

Disclaimer:
This information is for educational purposes only and not intended or implied to be personal medical advice. That is for your personal physician to provide after he or she accesses and reads each of the references above.
3
Cancer Research News & Studies / Metabolic Treatment of Cancer
« Last post by danialthomas on May 07, 2022, 09:21:30 am »
For those with aggressive stage-4 cancer, below is an aggressive metabolic (cancer-starving) treatment protocol. Weekly bloodwork (complete blood count, comprehensive metabolic panel, magnesium, phosphorus, and uric acid), weekly EKGs, and daily blood pressures should be monitored, and medication dosages adjusted along the way if necessary. This protocol is compatible with conventional cancer therapy and may serve as a stand-alone treatment to inhibit tumor growth and kill proliferating cancer cells, senescent (dormant) cancer cells, and cancer stem cells.

Diet:
Vegan (plant-based/low-methionine) and ketogenic (low-carbohydrate), 7 days per week. Make your meals using recipes from these cookbooks:

· Vegan Keto: ISBN-10: 1628603143
· Vegan Ketogenic Diet: ISBN-10: 164152653X
· The Keto Vegan: ISBN-10: 9492788306

Limit your eating to a 10-hour window period so that you are fasting 14 hours a day. For example, eat breakfast at 8:00 am and finish your last bite of food no later than 6:00 pm.
If you are losing weight and are too skinny (cachectic), to help put on weight, consume 1-2 tablespoons of organic MCT oil every 1-2 hours along with 1-2 capsules of conjugated bile acids to help digest the oil.

Dichloroacetate (DCA):
Taken Monday through Thursday only. Start at 10 mg/kg/day the first week and increase the dosage by an additional 10 mg/kg/day each week until you reach 20-40 mg/kg/day (more is better, depending on tolerance). Using a milligram scale, measure out and divide each day’s total dose into two half-doses and stir into 16 ounces of water and take immediately after breakfast and dinner.
Side effects of DCA may include heartburn, nausea, neuropathy, fatigue, confusion, and mood swings. These are kept to a minimum using omeprazole, curcumin, lactobacillus plantarum, MitoQ, and Poly-MVA (see below).

Supporting Medications:
· Diclofenac sodium 25-50 mg: One tablet immediately after breakfast, lunch, and dinner, Monday through Thursday only. Do not lie down for at least 10 minutes after taking this medication. Do not take ibuprofen while on diclofenac.
· Hydroxychloroquine 200 mg: One tablet with lunch, Monday through Thursday only. While taking this medication, you will need to perform an at-home EKG once a week using the AliveCor KardiaMobile device and email a copy of the EKG to your doctor to measure the QT interval. A normal QT interval is less than 450 milliseconds in men and less than 470 milliseconds in women.
· Ivermectin 3 mg: One tablet with breakfast, lunch, and dinner, Monday through Thursday only.
· Metformin ER 500 mg: One tablet with breakfast and dinner, Monday through Thursday only. If oral metformin causes undue nausea, switch to transdermal (topical) administration.
· Naltrexone 4.5 mg: One capsule at bedtime, Monday through Thursday only.
· Omeprazole 20 mg: One tablet 30 minutes before breakfast, Monday through Thursday only.
· Pentoxifylline 400 mg: One tablet with breakfast and dinner, Monday through Thursday only.
· Propranolol ER 60 mg: One tablet at bedtime, Monday through Thursday only. While taking this medication, you need to measure your blood pressure twice daily using a home blood pressure machine and report to your doctor if your blood pressure goes below 90/60.
· Simvastatin 20 mg: One tablet at bedtime, Monday through Thursday only.
· Tamoxifen 10 mg: One tablet daily with breakfast, Monday through Thursday only.
Supporting supplements:
· Aged garlic extract: Two capsules (692 mg total) at bedtime, Monday through Thursday only.
· Beta-hydroxybutyrate (exogenous ketones) 500mg: Four capsules 30 minutes before breakfast and lunch, and two capsules 30 minutes before dinner, 7 days per week.
· Citric acid: Using a milligram scale, measure out 1500 mg (1.5 grams) and stir in 8 ounces of water. Take immediately after breakfast, lunch, and dinner, Monday through Thursday only.
· Curcumin (highly bioavailable): One capsule (500 mg) daily with breakfast, 7 days a week.
· Fisetin (highly bioavailable): Take 7 capsules (311.5 mg total) all at once with breakfast on Monday only.
· Lactobacillus plantarum 1 billion CFUs: One tablet with lunch, 7 days a week.
· Magnesium gluconate 500 mg: One capsule with breakfast and dinner, 7 days a week.
· MitoQ (ubiquinol) 10 mg: One capsule with breakfast and dinner, Monday through Thursday only.
· Poly-MVA: Using a graduated cylinder, measure and stir 20 mL of Poly-MVA into 4 oz. of water and take 30 minutes before breakfast and dinner, Monday through Thursday only.
· Pro-resolving mediators 500 mg: One capsule with dinner, 7 days a week.
· Sodium selenite time-release 2 mg: Three tablets with breakfast, lunch, and dinner, 7 days a week.

Monitoring treatment effectiveness:
To verify the protocol is working as quickly as possible, get a baseline PET/CT scan and a follow-up scan every other month. If your insurance or Medicare plan does not cover the cost of the PET/CT scan, by going through RadiologyAssist.com, the discounted out-of-pocket cost ranges from $1300 to $2500, depending on where you live.

Continuation and Maintenance:
After achieving remission, in addition to maintaining a healthy diet, continue taking just DCA, but at a reduced dosage of 3 mg/kg/day, Monday through Thursday only. At this low dosage, side effects are minimal or absent altogether.
If additional aggressive steps are needed to help achieve remission, consider intravenous treatment using artesunate and high-dose vitamin C followed by solamargine and low-dose chemotherapy, together with hyperthermia.

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

For more information:
Anderson, P. Metabolic Therapies in Advanced “Salvage” Cancer Cases. Townsend Letter. August/September 2018: 39-43.
Barancik M, Bohacova V, Gibalova L, Sedlak J, Sulova Z, Breier A. Potentiation of anticancer drugs: effects of pentoxifylline on neoplastic cells. Int J Mol Sci. 2012;13(1):369-382.
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.
Capeloa T, Krzystyniak J, Rodriguez AC, Payen VL, Zampieri LX, Pranzini E, Derouane F, Vazeille T, Bouzin C, Duhoux FP, Murphy MP, Porporato PE, Sonveaux P. MitoQ Prevents Human Breast Cancer Recurrence and Lung Metastasis in Mice. Cancers (Basel). 2022 Mar 15;14(6):1488.
Castellanos-Esparza YC, Wu S, Huang L, Buquet C, Shen R, Sanchez-Gonzalez B, García Latorre EA, Boyer O, Varin R, Jiménez-Zamudio LA, Janin A, Vannier JP, Li H, Lu H. Synergistic promoting effects of pentoxifylline and simvastatin on the apoptosis of triple-negative MDA-MB-231 breast cancer cells. Int J Oncol. 2018 Apr;52(4):1246-1254.
Cham, B. (2017) Solasodine, Solamargine and Mixtures of Solasodine Rhamnosides: Pathway to Expansive Clinical Anticancer Therapies. International Journal of Clinical Medicine, 8, 692-713.
Chen H, Zhang H, Cao L, et al. Glucose Limitation Sensitizes Cancer Cells to Selenite-Induced Cytotoxicity via SLC7A11-Mediated Redox Collapse. Cancers (Basel). 2022;14(2):345.
Chen W, An J, Guo J, Wu Y, Yang L, Dai J, Gong K, Miao S, Xi S, Du J. Sodium selenite attenuates lung adenocarcinoma progression by repressing SOX2-mediated stemness. Cancer Chemother Pharmacol. 2018 May;81(5):885-895.
Dadali, T., Diers, A.R., Kazerounian, S. et al. Elevated levels of mitochondrial CoQ10 induce ROS-mediated apoptosis in pancreatic cancer. Sci Rep 11, 5749 (2021).
da Veiga Moreira J, Hamraz M, Abolhassani M, Schwartz L, Jolicœur M, Peres S. Metabolic therapies inhibit tumor growth in vivo and in silico. Sci Rep. 2019 Feb 28;9(1):3153.
De Preter G, Neveu MA, Danhier P, Brisson L, Payen VL, Porporato PE, Jordan BF, Sonveaux P, Gallez B. Inhibition of the pentose phosphate pathway by dichloroacetate unravels a missing link between aerobic glycolysis and cancer cell proliferation. Oncotarget. 2016 Jan 19;7(3):2910-20.
Di Bello E, Zwergel C, Mai A, Valente S. The Innovative Potential of Statins in Cancer: New Targets for New Therapies. Front Chem. 2020;8:516.
Ebrahimpour S, Tabari MA, Youssefi MR, Aghajanzadeh H, Behzadi MY. Synergistic effect of aged garlic extract and naltrexone on improving immune responses to experimentally induced fibrosarcoma tumor in BALB/c mice. Pharmacognosy Res. 2013 Jul;5(3):189-94.
Giordano A, Tommonaro G. Curcumin and Cancer. Nutrients. 2019;11(10):2376.
Golunski G, Woziwodzka A, Piosik J. Potential Use of Pentoxifylline in Cancer Therapy. Curr Pharm Biotechnol. 2018;19(3):206-216.
Hannon, G., Tansi, F.L., Hilger, I. and Prina-Mello, A. (2021), The Effects of Localized Heat on the Hallmarks of Cancer. Adv. Therap., 4: 2000267.
Hong SE, Jin HO, Kim HA, Seong MK, Kim EK, Ye SK, Choe TB, Lee JK, Kim JI, Park IC, Noh WC. Targeting HIF-1α is a prerequisite for cell sensitivity to dichloroacetate (DCA) and metformin. Biochem Biophys Res Commun. 2016 Jan 8;469(2):164-70.
Icard P, Coquerel A, Wu Z, et al. Understanding the Central Role of Citrate in the Metabolism of Cancer Cells and Tumors: An Update. Int J Mol Sci. 2021;22(12):6587.
Ishiguro T, Ishiguro RH, Ishiguro M, Toki A, Terunuma H. Synergistic Anti-tumor Effect of Dichloroacetate and Ivermectin. Cureus. 2022 Feb 3;14(2):e21884.
Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A. The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. Am J Cancer Res. 2018;8(2):317-331.
Kieliszek M, Lipinski B, Błażejak S. Application of Sodium Selenite in the Prevention and Treatment of Cancers. Cells. 2017 Oct 24;6(4):39.
Lee I, Boucher Y, Demhartner TJ, Jain RK. Changes in tumour blood flow, oxygenation and interstitial fluid pressure induced by pentoxifylline. Br J Cancer. 1994;69(3):492-496.
Lei Y, Yi Y, Liu Y, et al. Metformin targets multiple signaling pathways in cancer. Chin J Cancer. 2017;36(1):17.
Li Z, You Y, Griffin N, Feng J, Shan F. Low-dose naltrexone (LDN): A promising treatment in immune-related diseases and cancer therapy. Int Immunopharmacol. 2018 Aug;61:178-184.
Liang, Y., Hou, L., Li, L. et al. Dichloroacetate restores colorectal cancer chemosensitivity through the p53/miR-149-3p/PDK2-mediated glucose metabolic pathway. Oncogene 39, 469–485 (2020).
Liu C, Zheng J, Ou X, Han Y. Anti-cancer Substances and Safety of Lactic Acid Bacteria in Clinical Treatment. Front Microbiol. 2021;12:722052.
Liu T, Zhang J, Li K, Deng L, Wang H. Combination of an Autophagy Inducer and an Autophagy Inhibitor: A Smarter Strategy Emerging in Cancer Therapy. Front Pharmacol. 2020;11:408.
Lu X, Zhou D, Hou B, Liu QX, Chen Q, Deng XF, Yu ZB, Dai JG, Zheng H. Dichloroacetate enhances the antitumor efficacy of chemotherapeutic agents via inhibiting autophagy in non-small-cell lung cancer. Cancer Manag Res. 2018;10:1231-1241.
Mantle D, Heaton RA, Hargreaves IP. Coenzyme Q10 and Immune Function: An Overview. Antioxidants (Basel). 2021;10(5):759.
Mikami D, Kobayashi M, Uwada J, Yazawa T, Kamiyama K, Nishimori K, Nishikawa Y, Nishikawa S, Yokoi S, Taniguchi T, Iwano M. β-Hydroxybutyrate enhances the cytotoxic effect of cisplatin via the inhibition of HDAC/survivin axis in human hepatocellular carcinoma cells. J Pharmacol Sci. 2020 Jan;142(1):1-8.
Mycielska ME, Mohr MTJ, Schmidt K, et al. Potential Use of Gluconate in Cancer Therapy. Front Oncol. 2019;9:522.
Ong CP. High Dose Vitamin C and Low Dose Chemo Treatment. J Cancer Sci. 2018;5(1): 4.
Pantziarka P, Sukhatme V, Bouche G, Meheus L, Sukhatme VP. Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent. Ecancermedicalscience. 2016; 10:610.
Ren, JG., Seth, P., Ye, H. et al. Citrate Suppresses Tumor Growth in Multiple Models through Inhibition of Glycolysis, the Tricarboxylic Acid Cycle and the IGF-1R Pathway. Sci Rep 7, 4537 (2017).
Tataranni T, Piccoli C. Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications. Oxid Med Cell Longev. 2019;2019:8201079.
Wang B, Hou D, Liu Q, Wu T, Guo H, Zhang X, Zou Y, Liu Z, Liu J, Wei J, Gong Y, Shao C. Artesunate sensitizes ovarian cancer cells to cisplatin by downregulating RAD51. Cancer Biol Ther. 2015;16(10):1548-56.
Weber DD, Aminazdeh-Gohari S, Kofler B. Ketogenic diet in cancer therapy. Aging (Albany NY). 2018;10(2):164-165.
Xu R, Ji Z, Xu C, Zhu J. The clinical value of using chloroquine or hydroxychloroquine as autophagy inhibitors in the treatment of cancers: A systematic review and meta-analysis. Medicine (Baltimore). 2018 Nov;97(46):e12912.
Yang Y, Luo H, Hui K, et al. Selenite-induced autophagy antagonizes apoptosis in colorectal cancer cells in vitro and in vivo. Oncol Rep. 2016;35(3):1255-1264.
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.
Zhang Q, Zhu B, Li Y. Resolution of Cancer-Promoting Inflammation: A New Approach for Anticancer Therapy. Front Immunol. 2017 Feb 2;8:71.
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 treatment advice. That is for your personal physician to determine after he or she carefully studies each of the references above.
4
Even though I only treat aggressive, metastatic (stage 3 & 4) cancer, many people ask me what I would do to eradicate non-metastatic (stage 1 & 2) cancer, especially if they wanted to see if surgery, chemotherapy, and/or radiation could be avoided. My answer is, I would exploit cancer’s known addiction to iron1 by manipulating iron metabolism in cancer cells and cancer stem cells as follows:

Diet and Lifestyle:
Proper diet and lifestyle lay the foundation to eradicating cancer and preventing its return. To learn more: www.thomashealthblog.com/?p=14640

Oral Protocol:
1. Block cancer energy metabolism by using metformin plus syrosingopine2.
2. Inhibit cancer’s two main antioxidant defense systems (glutathione and thioredoxin reductase) by using curcumin3, fenugreek4, and piperlongumine5.
3. Inhibit carbonic anhydrase 9 (CAIX) to acidify the intracellular pH, disrupt redox homeostasis, and increase vulnerability to ferroptosis by using acetazolamide6.
4. Promote ferroptosis (iron-mediated, pro-oxidative cell death) by using pentoxifylline7,8 and simvastatin9. So as not to neglect other forms of cell death, use berberine10-14 and curcumin15 to promote apoptosis, autophagy, immunogenic cell death, necroptosis, pyroptosis, and paraptosis.
5. Promote removal of tumor-cell debris by using specialized pro-resolving mediators16.
6. Augment the immunomodulatory effects of hyperthermia (see below) by using Ganoderma lucidum (reishi extract)17-20.

Intravenous Protocol:
1. Promote cancer-selective accumulation of iron ions by using low-molecular-weight iron dextran21. This is followed by…
2. Induce ferritin-degrading ferritinophagy by using artesunate22to further promote cancer-selective accumulation of iron ions. This is followed by…
3. Local radiofrequency hyperthermia to selectively “super-heat” iron-loaded cancer tissue up to 47°C with minimal-to-no damage to normal tissue21.

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

References:

1.   Wang Y, Yu L, Ding J, Chen Y. Iron Metabolism in Cancer. Int J Mol Sci. 2018;20(1):95.
2.   Benjamin D, Robay D, Hindupur SK, Pohlmann J, Colombi M, El-Shemerly MY, Maira SM, Moroni C, Lane HA, Hall MN. Dual Inhibition of the Lactate Transporters MCT1 and MCT4 Is Synthetic Lethal with Metformin due to NAD+ Depletion in Cancer Cells. Cell Rep. 2018 Dec 11;25(11):3047-3058.e4.
3.   Sznarkowska A, Kostecka A, Meller K, Bielawski KP. Inhibition of cancer antioxidant defense by natural compounds. Oncotarget. 2017 Feb 28;8(9):15996-16016.
4.   Cosialls E, El Hage R, Dos Santos L, Gong C, Mehrpour M, Hamaï A. Ferroptosis: Cancer Stem Cells Rely on Iron until "to Die for" It. Cells. 2021 Nov 2;10(11):2981.
5.   Parama D, Rana V, Girisa S, Verma E, Daimary UD, Thakur KK, et al. The promising potential of piperlongumine as an emerging therapeutics for cancer. Explor Target Antitumor Ther. 2021;2:323-54.
6.   Li Z, Jiang L, Toyokuni S. Role of carbonic anhydrases in ferroptosis-resistance. Arch Biochem Biophys. 2020 Aug 15;689:108440.
7.   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.
8.   Lee I, Boucher Y, Demhartner TJ, Jain RK. Changes in tumour blood flow, oxygenation and interstitial fluid pressure induced by pentoxifylline. Br J Cancer. 1994;69(3):492-496.
9.   Jiang W, Hu JW, He XR, Jin WL, He XY. Statins: a repurposed drug to fight cancer. J Exp Clin Cancer Res. 2021 Jul 24;40(1):241.
10.   Yip NK, Ho WS. Berberine induces apoptosis via the mitochondrial pathway in liver cancer cells. Oncol Rep. 2013 Sep;30(3):1107-12.
11.   Liu J, Liu P, Xu T, et al. Berberine Induces Autophagic Cell Death in Acute Lymphoblastic Leukemia by Inactivating AKT/mTORC1 Signaling. Drug Des Devel Ther. 2020;14:1813-1823.
12.   Wang Y, Liu Y, Du X, Ma H, Yao J. The Anti-Cancer Mechanisms of Berberine: A Review. Cancer Manag Res. 2020;12:695-702.
13.   Liu L, Fan J, Ai G, Liu J, Luo N, Li C, Cheng Z. Berberine in combination with cisplatin induces necroptosis and apoptosis in ovarian cancer cells. Biol Res. 2019 Jul 18;52(1):37.
14.   Zhang C, Sheng J, Li G, et al. Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review. Front Pharmacol. 2020;10:1461.
15.   Lee D, Kim IY, Saha S, Choi KS. Paraptosis in the anti-cancer arsenal of natural products. Pharmacol Ther. 2016 Jun;162:120-33.
16.   Zhang Q, Zhu B, Li Y. Resolution of Cancer-Promoting Inflammation: A New Approach for Anticancer Therapy. Front Immunol. 2017 Feb 2;8:71.
17.   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.
18.   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.
19.   Song M, Li ZH, Gu HS, Tang RY, Zhang R, Zhu YL, Liu JL, Zhang JJ, Wang LY. Ganoderma lucidum Spore Polysaccharide Inhibits the Growth of Hepatocellular Carcinoma Cells by Altering Macrophage Polarity and Induction of Apoptosis. J Immunol Res. 2021 Mar 5;2021:6696606.
20.   Xia QH, Lu CT, Tong MQ, et al. Ganoderma Lucidum Polysaccharides Enhance the Abscopal Effect of Photothermal Therapy in Hepatoma-Bearing Mice Through Immunomodulatory, Anti-Proliferative, Pro-Apoptotic and Anti-Angiogenic. Front Pharmacol. 2021;12:648708.
21.   Chung, HJ., Kim, HJ. & Hong, ST. Iron-dextran as a thermosensitizer in radiofrequency hyperthermia for cancer treatment. Appl Biol Chem 62, 24 (2019).
22.   Chen G, Guo G, Zhou X, Chen H. Potential mechanism of ferroptosis in pancreatic cancer. Oncol Lett. 2020 Jan;19(1):579-587.

Disclaimer:

This information is for educational purposes only and is not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitor¬ing by your doctor. Therefore, Dr. Thomas cannot answer any questions regarding appropriateness in your situation nor give treatment advice. That is for your doctor to determine after he or she diligently reads each of the references above.
5
Cancer Research News & Studies / Fighting Cancer With Diet And Lifestyle
« Last post by danialthomas on February 20, 2022, 04:04:42 pm »
Proper diet is vital to recovering from cancer or any other chronic degen­era­tive disease. Numerous scientific studies over the years have shown that those who eat a low-methionine (plant-based) diet have a lower inci­dence of can­cer. Learn more by watching these short videos:

· https://youtu.be/0VX_oZBMSd4
· https://youtu.be/CVAog5_muNw

To further understand the importance of eating a whole-food, plant-based diet when fighting cancer, order the book How Not to Die by Dr. Michael Greger (ISBN-13: 978-1250066114) and read the introduction and the chapters on cancer.
To help make it easier to eat this way, I recommend the Forks Over Knives Cook­book (ISBN-13: ‎978-1615190614) along with the Forks Over Knives Meal Plan­ner app (www.forksoverknives.com/meal-planner). If you need more guidance when it comes to cooking and meal preparation, Forks Over Knives can help you become a plant-based chef with their excellent video instructional courses: www.forksoverknives.com/cooking-course. If you simply don’t have the time or the energy to make your own meals, check out Green Chef vegan meal delivery service: www.greenchef.com.
Unless you need to gain weight, reduce portion sizes. Keep grains to a minimum. As much as possible, eat only foods that are labeled “USDA Organic” and “Non-GMO Project Veri­fied.” Use only organic date sugar or molasses for sweetening. And incorporate foods like the ones shown below that are rich in cancer-fighting phytochemicals. Aim for 2 servings of fruit and 4 servings of vege­tables per day.

· Apples
· Arugula
· Blackberries
· Blueberries
· Broccoli
· Brussel sprouts
· Cabbage
· Carrots
· Cauliflower
· Chard
· Cranberries
· Grapes
· Green tea
· Kale
· Lentils
· Mushrooms
· Onions
· Parsley
· Pinto beans
· Pomegranate
· Radishes
· Raspberries
· Rosemary
· Strawberries
· Tomatoes
· Watercress

Ketogenic diets:
There is a lot of talk on the internet about using a ketogenic diet to fight cancer. In my expert medical opinion, it is best to avoid it, as the growth and spread of can­cer can be accelerated by excess ketones. It is best for the diet to be low in methionine (plant-based) with the carbohydrate level being reasonably low, but not to the point of putting you into a state of ketosis. To learn how to lower the glycemic load of foods that are starchy, please read my blog about resistance starches: www.thomashealthblog.com/?p=4404.

Intermittent fasting:
When it comes to fighting cancer, just as important as what you eat may be when you eat. Intermittent fasting or time-restricted feeding is an eating pattern that alternates between periods of prolonged fasting and eating. The most common pat­tern is to fast (not eat) for 18 hours per day and restrict your daily eating schedule to a 6-hour window of time. To learn more about intermittent fasting, please read my blog: www.thomashealthblog.com/?p=4374. If you need to gain weight, intermittent fasting is not advised.

Supplements:
· Multivitamin: Conventional cancer treatment can induce nutritional deficien­cies. Therefore, it is important to take a high-quality, iron-free (cancer loves iron), multivita­min and multimineral supplement. Recommended brand: MegaFood One Daily Iron Free. Recommended dosage: One tablet daily.
· Omega-3 fatty acids: Recommended brand: Freshfield Vegan Omega-3. Recommended dosage: One capsule twice daily.
· Probiotics: Recommended brand: Florastor. Recommended dosage: One capsule twice daily.

Exercise:
The anti-cancer effects of exercise (especially strength training) cannot be overesti­mated. The recommended exercise routine is the 30-Minute Express Workout, 3 days per week at your local Planet Fitness gym. If you do not live near Planet Fitness, you can do strength training at home using exercise bands. If you are una­ble to participate in strength training, a mod­ified walking pro­gram is recommended: www.thomashealthblog.com/?p=1269.

Stress Reduction:
Chronic stress promotes cancer. To help alleviate stress, spend 30 minutes a day doing something you like, such as having sex more often, soaking in a hot tub, visiting a friend, playing with your dog (if you don’t have a dog, adopt one; unconditional love is priceless), spending time outdoors, listening to soothing music, watching a funny movie, learning to meditate, getting a massage, counting to ten before losing your temper, and avoiding difficult people whenever possible.

Hydration:
It is extremely important to stay well hydrated during cancer treatment. Adequate hydration helps flush toxins out of the body and reduce common side effects of treatment. A good rule of thumb is to drink half of your body weight in ounces of water. For example, if you weigh 150 pounds, divide that number by 2. That equals 75 and that is the number of fluid ounces of water to drink per day.
For maximum health benefit, it is important that the water you drink and cook with, be filtered of toxins and molecularly “structured.” The recommended water filter that can do both is the AquaLiv Water System (www.aqualiv.com). Structured water is also known as EZ (exclusion-zone) water, H3O2, the fourth phase of water, and gel water. Struc­tured water is more absorbable, optimizing hydration and flushing out toxins. It has been championed by Dr. Gerald Pollack, PhD, renowned scientist and distin­guished professor of bioengineer­ing at the University of Washington (https://youtu.be/i-T7tCMUDXU).

Sleep
Chronic sleep deprivation is associated with a higher risk of cancer development. Lack of quality sleep can lead to immune suppression and production of cancer-stimulating inflammatory cytokines. The individual contributions of inadequate sleep, circadian rhythm disruption, and impairments of melatonin production and immune function to the initiation and promotion of cancer are being examined closer by scientists. Getting deep and undisturbed sleep in total darkness may be far more important than we realize. To learn how to fix the most common sleep issues, visit www.thomashealthblog.com/?p=3003.

Proper Breathing:
Chronic hypoxia (persistent lack of optimal tissue oxygenation) is a major driving force for cancer, heart disease, diabetes, chronic fatigue, anxiety, depression, and numerous other health conditions. Most people have habitual “over-breathing” or “hyperventilation” patterns at rest, such as chest breathing instead of diaphragmatic breathing, mouth breathing instead of nose breathing, and rapid and deep breathing instead of slow and shallow breathing. These abnormal breathing patterns lead to hypocapnia or decreased carbon dioxide (CO2) levels in the alveoli (lungs) and arterial blood. This lack of CO2 is harmful because it constricts blood vessels which leads to decreased perfusion of vital organs and, due to something called the Bohr Effect, impairs oxygen release from hemoglobin which leads to hypoxia. Fortunately, this can be reversed over time with proper breathing retraining exercises using a simple device called the Relaxator™ (see www.thomashealthblog.com/?p=13678).
It seems counterintuitive, but the more air one breathes, the lower the levels of CO2 and the less oxygen that reaches the tissues and is released to he cells. Having normal levels of CO2 in the alveoli (exhaled air) and arterial blood (40 mmHg or 5.3% at sea level) is crucial for good health. Numerous chronic diseases are associated with hypocapnia from over-breathing and the resultant tissue hypoxia. For example, in a 2001 Ukrainian study, 120 women with metastatic breast cancer were found to have an average of only 22 mmHg or 2.9% of CO2 in their exhaled air. In the same study, it was found that breathing retraining exercises reduced mortality in the women by nearly six-fold! It’s as if tumors are cries of the body for more oxygen. To promote normal breathing patterns, healthy CO2 levels, and optimal tissue oxygenation, I spend 15 minutes twice daily using the Relaxator™ while checking emails.

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

For more information:
Blask DE. Melatonin, sleep disturbance and cancer risk. Sleep Med Rev. 2009 Aug;13(4):257-64.
Bonuccelli G, Tsirigos A, Whitaker-Menezes D, et al. Ketones and lactate “fuel” tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle. 2010;9(17):3506-3514.
Cavuoto P, Fenech MF. A review of methionine dependency and the role of methi­onine restriction in cancer growth control and life-span extension. Cancer Treat Rev. 2012 Oct;38(6):726-36.
Dai S, Mo Y, Wang Y, Xiang B, Liao Q, Zhou M, Li X, Li Y, Xiong W, Li G, Guo C, Zeng Z. Chronic Stress Promote Cancer Development. Front Oncol. 2020 Aug 19;10:1492.
Dong D. Wang, Yanping Li, Shilpa N. Bhupathiraju, Bernard A. Rosner, Qi Sun, Edward L. Giovannucci, Eric B. Rimm, JoAnn E. Manson, Walter C. Willett, Meir J. Stampfer, Frank B. Hu. Fruit and Vegetable Intake and Mortality: Results From 2 Prospective Cohort Studies of US Men and Women and a Meta-Analysis of 26 Cohort Studies. Circulation, 2021.
Hwang SG, Lee HS, Lee BC, Bahng G. Effect of Antioxidant Water on the Bioac­tivities of Cells. Int J Cell Biol. 2017;2017:1917239.
Lee JH, Khor TO, Shu L, Su ZY, Fuentes F, Kong AN. Dietary phytochemicals and cancer prevention: Nrf2 signaling, epigenetics, and cell death mechanisms in blocking cancer initiation and progression. Pharmacol Ther. 2013 Feb;137(2):153-71.
Marinac CR, Nelson SH, Breen CI, Hartman SJ, Natarajan L, Pierce JP, Flatt SW, Sears DD, Patterson RE. Prolonged Nightly Fasting and Breast Cancer Prognosis. JAMA Oncol. 2016 Aug 1;2(8):1049-55.
Paschenko, SN. Study of application of the shallow breathing method in a combined treatment of breast cancer. Oncology (Kiev, Ukraine), 2001, v. 3, No.1, p. 77-78.

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 treatment advice. That is for your personal physician to determine after he or she carefully studies the references above.
6
Using data from over 300 patient tumors, UC San Francisco researchers have described 12 classes of “immune archetypes” to classify cancer tumors. Their findings, published this week in CELL, reveal that cancers from different parts of the body are immunologically similar to one another. These classifications provide unique strategies for enhancing each patient’s choice of cancer immunotherapies.

The UCSF researchers, led by first co-authors Alexis Combes, PhD, and Bushra Samad, MS, and senior author, Max Krummel, PhD, obtained tumor specimens from 78 UCSF clinicians, and surveyed 364 tumors biopsies from patients and categorized them into groups based on their immune microenvironment. Their findings offer a new way of looking at cancer immunotherapy that matches the immune environment around the tumor and points the way to personalized immunotherapies.

“This is a new framework for how to look at cancer patients,” said Combes, director of the D2B CoLab and incoming assistant professor in the Department of Pathology at UCSF. “This work will help clinicians find the right biology to target and avoid targeting cells that aren’t present in the tumor.”

Read more...
https://www.cancerhealth.com/article/sorting-cancers-by-immune-archetypes-may-offer-new-approach-precision-immunotherapy
7
Cancer Research News & Studies / Next-Generation Cancer Treatment
« Last post by danialthomas on January 16, 2022, 05:42:22 pm »
For those who fear chemotherapy because of its side effects or have become discouraged by chemotherapy because it stopped working, the protocol below should be considered. It builds upon my successes over the past 30+ years along with the recent successes of an overseas colleague of mine who has been combining high-dose vitamin C with low-dose chemotherapy and achieving rather impressive results. As a result of our co-collaboration, we believe that a combined approach will be even more effective.

Due to the low dose of chemotherapy drugs, treatment is generally well tolerated with most patients experiencing no severe side effects. The main side effect is nausea, and this is minimized by using ondansetron (Zofran).

Once-a-week, in-office treatment:

• Intravenous high-dose vitamin C plus doxycycline, azithromycin, and solamargine, along with hyperthermia to heat tumor tissue to 42°C. This is immediately followed by…
• Intravenous chemotherapy combining 3-5 synergistic drugs used for the cancer type at 1/3 to 1/5 the normal dose. This is combined with intravenous curcumin and additional hyperthermia at 42°C.
• The following morning, we do hyperthermia only. This time, heating tumor tissue to 45°C.

Supporting oral medications and supplements:

• Acetazolamide
• Aspirin
• Berberine
• Bromelain
• Fisetin
• Ivermectin
• Metformin
• Nattokinase
• Pentoxifylline
• Piperlongumine
• Reishi mushroom wall-broken spore powder
• Specialized pro-resolving mediators
• Syrosingopine

The scientific rationale for the protocol is broken down into these seven components:

1. Inhibit cancer metabolism (“starve” cancer): Metformin and syrosingopine1
2. Promote chemosensitivity and chemoprotection, and inhibit multi-drug resistance: Ivermectin2, pentoxifylline3, intravenous curcumin4,5
3. Overcome barriers to treatment by targeting conditions in the tumor microenvironment that impede intratumoral distribution of anticancer compounds and promote immune evasion:

• Hypoperfusion and hypoxia: Pentoxifylline6, hyperthermia at 42°C7
• Elevated tumor fluid pressure: Pentoxifylline6, hyperthermia at 42°C8
• Extracellular acidification: Metformin and syrosingopine1, acetazolamide9
• Inflammation: Berberine10, specialized pro-resolving mediators11
• Fibrin clots: Bromelain12, nattokinase13

4. Kill proliferating (active) cancer cells by inducing six different forms of cell death:

• Apoptosis: Berberine14, reishi extract15, intravenous vitamin C and low-dose chemotherapy15 with solamargine17 and hyperthermia7
• Autophagy: Berberine18, piperlongumine19
• Ferroptosis: Acetazolamide20,21, piperlongumine22
• Immunogenic cell death: Berberine10, piperlongumine23, reishi extract24-26, intravenous solamargine17, hyperthermia at 45°C27
• Necroptosis: Berberine28, hyperthermia at 45°C7
• Pyroptosis: Metformin29, berberine29

5. Kill senescent (dormant) cancer cells: Fisetin31, piperlongumine32, intravenous solamargine17
6. Eradicate cancer stem cells: Intravenous vitamin C plus azithromycin and doxycycline33
7. Promote phagocytic removal of tumor debris: Aspirin34, specialized pro-resolving mediators11

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

References:

1. Benjamin D, Robay D, Hindupur SK, Pohlmann J, Colombi M, El-Shemerly MY, Maira SM, Moroni C, Lane HA, Hall MN. Dual Inhibition of the Lactate Transporters MCT1 and MCT4 Is Synthetic Lethal with Metformin due to NAD+ Depletion in Cancer Cells. Cell Rep. 2018 Dec 11;25(11):3047-3058.e4.
2. Jiang L, Wang P, Sun YJ, Wu YJ. Ivermectin reverses the drug resistance in cancer cells through EGFR/ERK/Akt/NF-κB pathway. J Exp Clin Cancer Res. 2019 Jun 18;38(1):265.
3. Barancik M, Bohacova V, Gibalova L, Sedlak J, Sulova Z, Breier A. Potentiation of anticancer drugs: effects of pentoxifylline on neoplastic cells. Int J Mol Sci. 2012;13(1):369-382.
4. Tang XQ, Bi H, Feng JQ, Cao JG. Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR. Acta Pharmacol Sin. 2005 Aug;26(8):1009-16.
5. Liu Z, Huang P, Law S, Tian H, Leung W, Xu C. Preventive Effect of Curcumin Against Chemotherapy-Induced Side-Effects. Front Pharmacol. 2018;9:1374.
6. Lee I, Boucher Y, Demhartner TJ, Jain RK. Changes in tumour blood flow, oxygenation and interstitial fluid pressure induced by pentoxifylline. Br J Cancer. 1994;69(3):492-496.
7. Hannon, G., Tansi, F.L., Hilger, I. and Prina-Mello, A. (2021), The Effects of Localized Heat on the Hallmarks of Cancer. Adv. Therap., 4: 2000267.
8. Leunig M, Goetz AE, Dellian M, Zetterer G, Gamarra F, Jain RK, Messmer K. Interstitial fluid pressure in solid tumors following hyperthermia: possible correlation with therapeutic response. Cancer Res. 1992 Jan 15;52(2):487-90.
9. Lee SH, McIntyre D, Honess D, Hulikova A, Pacheco-Torres J, Cerdán S, Swietach P, Harris AL, Griffiths JR. Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in vivo. Br J Cancer. 2018 Aug;119(5):622-630.
10. Wang Y, Liu Y, Du X, Ma H, Yao J. The Anti-Cancer Mechanisms of Berberine: A Review. Cancer Manag Res. 2020;12:695-702.
11. Zhang Q, Zhu B, Li Y. Resolution of Cancer-Promoting Inflammation: A New Approach for Anticancer Therapy. Front Immunol. 2017 Feb 2;8:71.
12. Pavan R, Jain S, Shraddha, Kumar A. Properties and therapeutic application of bromelain: a review. Biotechnol Res Int. 2012;2012:976203.
13. Altaf F, Wu S, Kasim V. Role of Fibrinolytic Enzymes in Anti-Thrombosis Therapy. Front Mol Biosci. 2021;8:680397.
14. Yip NK, Ho WS. Berberine induces apoptosis via the mitochondrial pathway in liver cancer cells. Oncol Rep. 2013 Sep;30(3):1107-12.
15. Wu X, Jiang L, Zhang Z, He Y, Teng Y, Li J, Yuan S, Pan Y, Liang H, Yang H, Zhou P. Pancreatic cancer cell apoptosis is induced by a proteoglycan extracted from Ganoderma lucidum. Oncol Lett. 2021 Jan;21(1):34.
16. Ong CP. High Dose Vitamin C and Low Dose Chemo Treatment. J Cancer Sci. 2018;5(1): 4.
17. Cham, B. (2017) Solasodine, Solamargine and Mixtures of Solasodine Rhamnosides: Pathway to Expansive Clinical Anticancer Therapies. International Journal of Clinical Medicine, 8, 692-713.
18. Liu J, Liu P, Xu T, et al. Berberine Induces Autophagic Cell Death in Acute Lymphoblastic Leukemia by Inactivating AKT/mTORC1 Signaling. Drug Des Devel Ther. 2020;14:1813-1823.
19. 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.
20. 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.
21. 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.
22. 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.
23. Afolabi LO, Bi J, Chen L, Wan X. A natural product, Piperlongumine (PL), increases tumor cells sensitivity to NK cell killing. Int Immunopharmacol. 2021 Jul;96:107658.
24. 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.
25. 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.
26. Song M, Li ZH, Gu HS, Tang RY, Zhang R, Zhu YL, Liu JL, Zhang JJ, Wang LY. Ganoderma lucidum Spore Polysaccharide Inhibits the Growth of Hepatocellular Carcinoma Cells by Altering Macrophage Polarity and Induction of Apoptosis. J Immunol Res. 2021 Mar 5;2021:6696606.
27. Toraya-Brown S, Fiering S. Local tumour hyperthermia as immunotherapy for metastatic cancer. Int J Hyperthermia. 2014;30(8):531-539.
28. Liu L, Fan J, Ai G, Liu J, Luo N, Li C, Cheng Z. Berberine in combination with cisplatin induces necroptosis and apoptosis in ovarian cancer cells. Biol Res. 2019 Jul 18;52(1):37.
29. Wang L, Qin X, Liang J, Ge P. Induction of Pyroptosis: A Promising Strategy for Cancer Treatment. Front Oncol. 2021 Feb 26;11:635774.
30. Zhang C, Sheng J, Li G, et al. Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review. Front Pharmacol. 2020;10:1461.
31. 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.
32. Wang Y, Chang J, Liu X, et al. Discovery of piperlongumine as a potential novel lead for the development of senolytic agents. Aging (Albany NY). 2016;8(11):2915-2926.
33. 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(8):2202-2216.
34. Dalli J, Winkler JW, Colas RA, Arnardottir H, Cheng CY, Chiang N, Petasis NA, Serhan CN. Resolvin D3 and aspirin-triggered resolvin D3 are potent immunoresolvents. Chem Biol. 2013 Feb 21;20(2):188-201.

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, Dr. Thomas 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 each of the references above.
8
Cancer Research News & Studies / A Fresh Look at Chemotherapy
« Last post by danialthomas on December 10, 2021, 05:33:38 pm »
My job as a physician is to do what it takes to help my cancer patient achieve remission. For those who fear chemotherapy because of its side effects or have become discouraged by chemotherapy because it eventually stopped working, the protocol below should be considered. Due to the low dose of chemotherapy drugs used, treatment is generally well tolerated with most patients experiencing no severe side effects.

Once-a-week, in-office treatment:
• Intravenous artesunate immediately followed by…
• Intravenous high-dose vitamin C plus doxycycline and azithromycin immediately followed by…
• Intravenous chemotherapy combining 3-5 synergistic drugs used for the cancer type at 1/3 to 1/5 the normal dose. This is combined with intravenous curcumin to decrease chemoresistance and reduce chemotherapy side effects, along with hyperthermia to improve drug delivery, disable the intracellular DNA repair enzymes that allow cancer to survive chemotherapy, and induce cancer cells to release heat-shock proteins and tumor-specific antigens that attract cancer-killing tumor-infiltrating lymphocytes and Natural Killer cells.

Supporting oral protocol:
• Ivermectin and pentoxifylline to promote chemosensitivity and inhibit chemoresistance
• Piperlongumine to impair cancer’s thioredoxin and glutathione antioxidant defense mechanisms
• Luteolin to promote cell cycle arrest and apoptosis
• Metformin and syrosingopine to impair cancer bioenergetics
• Low-dose naltexone to enhance the immune response against cancer
• Pro-resolving mediators to promote the removal of tumor debris

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

References:

Benjamin D, Robay D, Hindupur SK, Pohlmann J, Colombi M, El-Shemerly MY, Maira SM, Moroni C, Lane HA, Hall MN. Dual Inhibition of the Lactate Transporters MCT1 and MCT4 Is Synthetic Lethal with Metformin due to NAD+ Depletion in Cancer Cells. Cell Rep. 2018 Dec 11;25(11):3047-3058.e4.
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(8):2202-2216.
Golunski G, Woziwodzka A, Piosik J. Potential Use of Pentoxifylline in Cancer Therapy. Curr Pharm Biotechnol. 2018;19(3):206-216.
Hannon, G., Tansi, F.L., Hilger, I. and Prina-Mello, A. (2021), The Effects of Localized Heat on the Hallmarks of Cancer. Adv. Therap., 4: 2000267.
Imran M, Rauf A, Abu-Izneid T, Nadeem M, Shariati MA, Khan IA, Imran A, Orhan IE, Rizwan M, Atif M, Gondal TA, Mubarak MS. Luteolin, a flavonoid, as an anticancer agent: A review. Biomed Pharmacotherapy. 2019 Apr;112:108612.
Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A. The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. Am J Cancer Res. 2018;8(2):317-331.
Li Z, You Y, Griffin N, Feng J, Shan F. Low-dose naltrexone (LDN): A promising treatment in immune-related diseases and cancer therapy. Int Immunopharmacol. 2018 Aug;61:178-184.
Liu Z, Huang P, Law S, Tian H, Leung W, Xu C. Preventive Effect of Curcumin Against Chemotherapy-Induced Side-Effects. Front Pharmacol. 2018 Nov 27;9:1374.
Ong CP. High Dose Vitamin C and Low Dose Chemo Treatment. J Cancer Sci. 2018;5(1): 4.
Shaikh S, Shaikh J, Naba YS, Doke K, Ahmed K, Yusufi M. Curcumin: reclaiming the lost ground against cancer resistance. Cancer Drug Resist 2021;4:298-320.
Slezakova S, Ruda-Kucerova J. Anticancer Activity of Artemisinin and its Derivatives. Anticancer Res. 2017 Nov;37(11):5995-6003.
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.
Zhang Q, Zhu B, Li Y. Resolution of Cancer-Promoting Inflammation: A New Approach for Anticancer Therapy. Front Immunol. 2017 Feb 2;8:71.

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 treatment advice. That is for your personal physician to determine after he or she carefully studies the references above.
9
There are two things most people believe about lung cancer, says Jamie Studts, PhD, co-leader of the Cancer Prevention & Control Program at the University of Colorado (CU) Cancer Center: Those who suffer from it most likely caused it by using tobacco, and the prognosis for surviving the disease is poor.

While neither of those things is strictly true, the common perception of lung cancer means that those who survive it often do so alone, without the sense of community and togetherness that is the norm for many survivors of breast cancer, colorectal cancer, and other cancers.

That’s why, when he served as professor of behavioral science at the University of Kentucky Markey Cancer Center, Studts led the development of an intervention to help support lung cancer survivors through their survivorship journey.

Read more:
https://www.cancerhealth.com/article/improving-survivorship-individuals-diagnosed-lung-cancer
10
Cancer Research News & Studies / Eggplant To The Rescue
« Last post by danialthomas 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.
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