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  1. Article: Case report: Resolution of malignant canine mast cell tumor using ketogenic metabolic therapy alone.

    Seyfried, Thomas N / Mukherjee, Purna / Lee, Derek C / Ta, Linh / Nations, Loren

    Frontiers in nutrition

    2023  Volume 10, Page(s) 1157517

    Abstract: Background: Mast cell tumors (MCT) are common neoplasms in dogs and are similar to most other malignant cancers in requiring glucose for growth, regardless of histological grade. Ketogenic metabolic therapy (KMT) is emerging as a non-toxic nutritional ... ...

    Abstract Background: Mast cell tumors (MCT) are common neoplasms in dogs and are similar to most other malignant cancers in requiring glucose for growth, regardless of histological grade. Ketogenic metabolic therapy (KMT) is emerging as a non-toxic nutritional intervention for cancer management in animals and humans alike. We report the case of a 7 years-old Pit Bull terrier that presented in 2011 with a cutaneous mast cell tumor under the right nostril.
    Methods: The patient's parent refused standard of care (SOC) and steroid medication after initial tumor diagnosis due to the unacceptable adverse effects of these treatments. Following tumor diagnosis, the patient's diet was switched from Ol'Roy dog food to raw vegetables with cooked fish. The tumor continued to grow on this diet until July, 2013 when the diet was switched to a carbohydrate free, raw calorie restricted ketogenic diet consisting mostly of chicken and oils. A dog food calculator was used to reduce calories to 60% (40% calorie restriction) of that consumed on the original diet. A total of 444 kilocalories were given twice/day at 12 h intervals with one medium-sized raw radish given as a treat between each meal.
    Results: The tumor grew to about 3-4 cm and invaded surrounding tissues while the patient was on the raw vegetable, cooked fish diet. The tumor gradually disappeared over a period of several months when the patient was switched to the carbohydrate free calorie restricted ketogenic diet. The patient lost 2.5 kg during the course of the calorie restriction and maintained an attentive and active behavior. The patient passed away without pain on June 4, 2019 (age 15 years) from failure to thrive due to an enlarged heart with no evidence of mast cell tumor recurrence.
    Conclusion: This is the first report of a malignant cutaneous mast cell tumor in a dog treated with KMT alone. The resolution of the tumor in this canine patient could have been due to the diet-induced energy stress and the restriction of glucose-driven aerobic fermentation that is essential for the growth of most malignant tumors. Further studies are needed to determine if this non-toxic dietary therapeutic strategy could be effective in managing other canine patients with malignant mast cell tumors.
    Language English
    Publishing date 2023-03-28
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2776676-7
    ISSN 2296-861X
    ISSN 2296-861X
    DOI 10.3389/fnut.2023.1157517
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: On the Origin of ATP Synthesis in Cancer.

    Seyfried, Thomas N / Arismendi-Morillo, Gabriel / Mukherjee, Purna / Chinopoulos, Christos

    iScience

    2020  Volume 23, Issue 11, Page(s) 101761

    Abstract: ATP is required for mammalian cells to remain viable and to perform genetically programmed functions. Maintenance of the ΔG' ...

    Abstract ATP is required for mammalian cells to remain viable and to perform genetically programmed functions. Maintenance of the ΔG'
    Language English
    Publishing date 2020-11-02
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2020.101761
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of

    Seyfried, Thomas N / Shivane, Aditya G / Kalamian, Miriam / Maroon, Joseph C / Mukherjee, Purna / Zuccoli, Giulio

    Frontiers in nutrition

    2021  Volume 8, Page(s) 682243

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2021-05-31
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2776676-7
    ISSN 2296-861X
    ISSN 2296-861X
    DOI 10.3389/fnut.2021.682243
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Metabolic management of microenvironment acidity in glioblastoma.

    Seyfried, Thomas N / Arismendi-Morillo, Gabriel / Zuccoli, Giulio / Lee, Derek C / Duraj, Tomas / Elsakka, Ahmed M / Maroon, Joseph C / Mukherjee, Purna / Ta, Linh / Shelton, Laura / D'Agostino, Dominic / Kiebish, Michael / Chinopoulos, Christos

    Frontiers in oncology

    2022  Volume 12, Page(s) 968351

    Abstract: Glioblastoma (GBM), similar to most cancers, is dependent on fermentation metabolism for the synthesis of biomass and energy (ATP) regardless of the cellular or genetic heterogeneity seen within the tumor. The transition from respiration to fermentation ... ...

    Abstract Glioblastoma (GBM), similar to most cancers, is dependent on fermentation metabolism for the synthesis of biomass and energy (ATP) regardless of the cellular or genetic heterogeneity seen within the tumor. The transition from respiration to fermentation arises from the documented defects in the number, the structure, and the function of mitochondria and mitochondrial-associated membranes in GBM tissue. Glucose and glutamine are the major fermentable fuels that drive GBM growth. The major waste products of GBM cell fermentation (lactic acid, glutamic acid, and succinic acid) will acidify the microenvironment and are largely responsible for drug resistance, enhanced invasion, immunosuppression, and metastasis. Besides surgical debulking, therapies used for GBM management (radiation, chemotherapy, and steroids) enhance microenvironment acidification and, although often providing a time-limited disease control, will thus favor tumor recurrence and complications. The simultaneous restriction of glucose and glutamine, while elevating non-fermentable, anti-inflammatory ketone bodies, can help restore the pH balance of the microenvironment while, at the same time, providing a non-toxic therapeutic strategy for killing most of the neoplastic cells.
    Language English
    Publishing date 2022-08-17
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.968351
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer.

    Meidenbauer, Joshua J / Mukherjee, Purna / Seyfried, Thomas N

    Nutrition & metabolism

    2015  Volume 12, Page(s) 12

    Abstract: Background: Metabolic therapy using ketogenic diets (KD) is emerging as an alternative or complementary approach to the current standard of care for brain cancer management. This therapeutic strategy targets the aerobic fermentation of glucose (Warburg ... ...

    Abstract Background: Metabolic therapy using ketogenic diets (KD) is emerging as an alternative or complementary approach to the current standard of care for brain cancer management. This therapeutic strategy targets the aerobic fermentation of glucose (Warburg effect), which is the common metabolic malady of most cancers including brain tumors. The KD targets tumor energy metabolism by lowering blood glucose and elevating blood ketones (β-hydroxybutyrate). Brain tumor cells, unlike normal brain cells, cannot use ketone bodies effectively for energy when glucose becomes limiting. Although plasma levels of glucose and ketone bodies have been used separately to predict the therapeutic success of metabolic therapy, daily glucose levels can fluctuate widely in brain cancer patients. This can create difficulty in linking changes in blood glucose and ketones to efficacy of metabolic therapy.
    Methods: A program was developed (Glucose Ketone Index Calculator, GKIC) that tracks the ratio of blood glucose to ketones as a single value. We have termed this ratio the Glucose Ketone Index (GKI).
    Results: The GKIC was used to compute the GKI for data published on blood glucose and ketone levels in humans and mice with brain tumors. The results showed a clear relationship between the GKI and therapeutic efficacy using ketogenic diets and calorie restriction.
    Conclusions: The GKIC is a simple tool that can help monitor the efficacy of metabolic therapy in preclinical animal models and in clinical trials for malignant brain cancer and possibly other cancers that express aerobic fermentation.
    Language English
    Publishing date 2015-03-11
    Publishing country England
    Document type Journal Article
    ISSN 1743-7075
    ISSN 1743-7075
    DOI 10.1186/s12986-015-0009-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer

    Meidenbauer, Joshua J / Mukherjee, Purna / Seyfried, Thomas N

    Nutrition & metabolism. 2015 Dec., v. 12, no. 1

    2015  

    Abstract: BACKGROUND: Metabolic therapy using ketogenic diets (KD) is emerging as an alternative or complementary approach to the current standard of care for brain cancer management. This therapeutic strategy targets the aerobic fermentation of glucose (Warburg ... ...

    Abstract BACKGROUND: Metabolic therapy using ketogenic diets (KD) is emerging as an alternative or complementary approach to the current standard of care for brain cancer management. This therapeutic strategy targets the aerobic fermentation of glucose (Warburg effect), which is the common metabolic malady of most cancers including brain tumors. The KD targets tumor energy metabolism by lowering blood glucose and elevating blood ketones (β-hydroxybutyrate). Brain tumor cells, unlike normal brain cells, cannot use ketone bodies effectively for energy when glucose becomes limiting. Although plasma levels of glucose and ketone bodies have been used separately to predict the therapeutic success of metabolic therapy, daily glucose levels can fluctuate widely in brain cancer patients. This can create difficulty in linking changes in blood glucose and ketones to efficacy of metabolic therapy. METHODS: A program was developed (Glucose Ketone Index Calculator, GKIC) that tracks the ratio of blood glucose to ketones as a single value. We have termed this ratio the Glucose Ketone Index (GKI). RESULTS: The GKIC was used to compute the GKI for data published on blood glucose and ketone levels in humans and mice with brain tumors. The results showed a clear relationship between the GKI and therapeutic efficacy using ketogenic diets and calorie restriction. CONCLUSIONS: The GKIC is a simple tool that can help monitor the efficacy of metabolic therapy in preclinical animal models and in clinical trials for malignant brain cancer and possibly other cancers that express aerobic fermentation.
    Keywords 3-hydroxybutyric acid ; animal models ; blood ; blood glucose ; brain ; clinical trials ; energy ; fermentation ; glucose ; humans ; ketogenic diet ; ketone bodies ; ketones ; mice ; neoplasms ; patients ; therapeutics
    Language English
    Dates of publication 2015-12
    Size p. 9.
    Publishing place Springer-Verlag
    Document type Article
    ZDB-ID 2160376-5
    ISSN 1743-7075
    ISSN 1743-7075
    DOI 10.1186/s12986-015-0009-2
    Database NAL-Catalogue (AGRICOLA)

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  7. Article: Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer.

    Seyfried, Thomas N / Mukherjee, Purna / Iyikesici, Mehmet S / Slocum, Abdul / Kalamian, Miriam / Spinosa, Jean-Pierre / Chinopoulos, Christos

    Frontiers in nutrition

    2020  Volume 7, Page(s) 21

    Abstract: Breast cancer remains as a significant cause of morbidity and mortality in women. Ultrastructural and biochemical evidence from breast biopsy tissue and cancer cells shows mitochondrial abnormalities that are incompatible with energy production through ... ...

    Abstract Breast cancer remains as a significant cause of morbidity and mortality in women. Ultrastructural and biochemical evidence from breast biopsy tissue and cancer cells shows mitochondrial abnormalities that are incompatible with energy production through oxidative phosphorylation (OxPhos). Consequently, breast cancer, like most cancers, will become more reliant on substrate level phosphorylation (fermentation) than on oxidative phosphorylation (OxPhos) for growth consistent with the mitochondrial metabolic theory of cancer. Glucose and glutamine are the prime fermentable fuels that underlie therapy resistance and drive breast cancer growth through substrate level phosphorylation (SLP) in both the cytoplasm (Warburg effect) and the mitochondria (Q-effect), respectively. Emerging evidence indicates that ketogenic metabolic therapy (KMT) can reduce glucose availability to tumor cells while simultaneously elevating ketone bodies, a non-fermentable metabolic fuel. It is suggested that KMT would be most effective when used together with glutamine targeting. Information is reviewed for suggesting how KMT could reduce systemic inflammation and target tumor cells without causing damage to normal cells. Implementation of KMT in the clinic could improve progression free and overall survival for patients with breast cancer.
    Language English
    Publishing date 2020-03-11
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2776676-7
    ISSN 2296-861X
    ISSN 2296-861X
    DOI 10.3389/fnut.2020.00021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Nontoxic Targeting of Energy Metabolism in Preclinical VM-M3 Experimental Glioblastoma.

    Augur, Zachary M / Doyle, Catherine M / Li, Mingyi / Mukherjee, Purna / Seyfried, Thomas N

    Frontiers in nutrition

    2018  Volume 5, Page(s) 91

    Abstract: Introduction: ...

    Abstract Introduction:
    Language English
    Publishing date 2018-10-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2776676-7
    ISSN 2296-861X
    ISSN 2296-861X
    DOI 10.3389/fnut.2018.00091
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Ganglioside GM3 Is Antiangiogenic in Malignant Brain Cancer.

    Seyfried, Thomas N / Mukherjee, Purna

    Journal of oncology

    2010  Volume 2010, Page(s) 961243

    Abstract: Progression of malignant brain tumors is dependent upon vascularity and is associated with altered ganglioside composition and distribution. Evidence is reviewed showing that the simple monosialoganglioside, GM3, possesses powerful antiangiogenic action ... ...

    Abstract Progression of malignant brain tumors is dependent upon vascularity and is associated with altered ganglioside composition and distribution. Evidence is reviewed showing that the simple monosialoganglioside, GM3, possesses powerful antiangiogenic action against the highly vascularized CT-2A mouse astrocytoma, which primarily expresses complex gangliosides. Brain tumors expressing high levels of GM3 are generally less vascularized and grow slower than tumors that express low levels of GM3. GM3 inhibits angiogenesis through autocrine and paracrine effects on vascular endothelial growth factor (VEGF) and associated receptors. GM3 should be a clinically useful compound for managing brain tumor angiogenesis.
    Language English
    Publishing date 2010-06-20
    Publishing country Egypt
    Document type Journal Article
    ZDB-ID 2461349-6
    ISSN 1687-8469 ; 1687-8450
    ISSN (online) 1687-8469
    ISSN 1687-8450
    DOI 10.1155/2010/961243
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Light- and Melanin Nanoparticle-Induced Cytotoxicity in Metastatic Cancer Cells.

    Gabriele, Victoria R / Mazhabi, Robabeh M / Alexander, Natalie / Mukherjee, Purna / Seyfried, Thomas N / Nwaji, Njemuwa / Akinoglu, Eser M / Mackiewicz, Andrzej / Zhou, Guofu / Giersig, Michael / Naughton, Michael J / Kempa, Krzysztof

    Pharmaceutics

    2021  Volume 13, Issue 7

    Abstract: Melanin nanoparticles are known to be biologically benign to human cells for a wide range of concentrations in a high glucose culture nutrition. Here, we show cytotoxic behavior at high nanoparticle and low glucose concentrations, as well as at low ... ...

    Abstract Melanin nanoparticles are known to be biologically benign to human cells for a wide range of concentrations in a high glucose culture nutrition. Here, we show cytotoxic behavior at high nanoparticle and low glucose concentrations, as well as at low nanoparticle concentration under exposure to (nonionizing) visible radiation. To study these effects in detail, we developed highly monodispersed melanin nanoparticles (both uncoated and glucose-coated). In order to study the effect of significant cellular uptake of these nanoparticles, we employed three cancer cell lines: VM-M3, A375 (derived from melanoma), and HeLa, all known to exhibit strong macrophagic character, i.e., strong nanoparticle uptake through phagocytic ingestion. Our main observations are: (i) metastatic VM-M3 cancer cells massively ingest melanin nanoparticles (mNPs); (ii) the observed ingestion is enhanced by coating mNPs with glucose; (iii) after a certain level of mNP ingestion, the metastatic cancer cells studied here are observed to die-glucose coating appears to slow that process; (iv) cells that accumulate mNPs are much more susceptible to killing by laser illumination than cells that do not accumulate mNPs; and (v) non-metastatic VM-NM1 cancer cells also studied in this work do not ingest the mNPs, and remain unaffected after receiving identical optical energy levels and doses. Results of this study could lead to the development of a therapy for control of metastatic stages of cancer.
    Language English
    Publishing date 2021-06-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics13070965
    Database MEDical Literature Analysis and Retrieval System OnLINE

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