Raadpleeg ook literatuurlijst niet-toxische stoffen en behandelingen bij specifiek hersentumoren en uitzaaiingen in de hersenen van arts-bioloog drs. Engelbert Valstar. 

Lees ook andere ervaringsverhalen in gerelateerde artikelen.

Ook uit deze studie blijkt dat een kytogeen dieet bij met name hersentumoren goede resultaten kan geven: Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned

19 november 2018: Bron: . 2018; 5: 20. Published online 2018 Mar 29.

Hier een tot in detail beschreven case studie van een 38-jarige man die in februari 2016 werd geconfronteerd met een niet volledige operabele hersentumor van het type Glioblastoma multiforme. Naast een wakkere operatie waar zoveel mogelijk tumorweefsel werd weggehaald, maar niet alles, is de man ook bestraald en heeft hij chemo (temozolomide - temodal) gekregen als standaard behandeling voor deze vorm en stadium van een glioblastoma.

Wat het echter bijzonder maakt is dat de man vooraf aan de operatie (hij werd pas 43 dagen later geopereerd) en ook daarna onder professionele begeleiding is begonnen met een op zijn persoonlijke situatie aangepast kytogeen dieet met daarbij ook aanvullende vitamines en mineralen waar nodig. Zo gebruikte de man ook een tijdje metformin en vitamine D bv. De man werd heel intensief begeleid en zijn bloedwaarden bv. werden heel regelmatig gemeten en mocht het nodig zijn werd zijn dieet en vitamines aangepast.

En met groot succes want op moment van publicatie van de case studie (maart 2018, dus ruim 2 jaar al) was de man nog steeds kankervrij, waren er geen tekenen van een recidief en was de man zijn lichamelijke conditie op de schaal van Karnofsky 100%. Wat duidt op een uitstekende conditie.

Bedenk  daarbij dat de mediane overall overleving van patiënten met een hersentumor van het type glioblastoma met standaard behandelingen ligt tussen de 12 en 14 maanden. Zelfs na een volledige operatie overleven mensen zelden 3 jaar. 

Hier een schema dat de man aanhield de eerste 9 maanden.

An external file that holds a picture, illustration, etc.
Object name is fnut-05-00020-g001.jpg

Figure 1

(A) Timeline of clinical course with dates of dietary treatments, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and hyperbaric oxygen therapy (HBOT). (B) Glucose/ketone index indicates the ratio of circulating glucose to urinary ketones at all eight clinical assessments during the 15 months period from February 2016 to April 2017.

Onderstaande grafiek laat zien wat de effecten waren op bepaalde waarden in zijn bloed:

Table 1

Influence of ketogenic metabolic therapy (KMT) on the patient’s biomarkers.

Before KMT/first presentationAfter KMT/before surgeryKMT continued/after surgery (months)
Biomarkers 3 9 15 20
Hb (g/dL) 11.0 12.5 13.0 12.9 13.1 16.1
WBC/μL blood 5,000 4,200 3,200 4,500 5,500 4,200
Platelets/μL blood 162,000 171,000 220,000 280,000 310,000 186,000
Cholesterol (mg/dL) 115 168 170 225
LDL (mg/dL) 50 103 106 159
HDL (mg/dL) 34 48 51 62
TG (mg/dL) 155 83 81 101
25(OH)D3 (ng/dL) 3.1 18.0 32.0 48.0 55.0 42.0
Homocysteine (μM) 19.2 16.0 14.9 12.0 9.4 11.9
Fasting glucose (mg/dL) 89 72 64 75 71 65
Fasting insulin (μIU/mL) 13.10 6.50 5.00 4.10 3.80 2.11
Urine ketones UD +++ +++ ++ + ++
Weight (kg) 71.1 67.7 56.9 66.2 61.8
BMI (kg/m2) 25.10 23.70 19.90 23.17 21.60

UD, undetectable.

De man zijn lichamelijke conditie ging sterk vooruit en bleef uitstekend.

In de conclusie van de studie schrijven de onderzoekers o.a. dit: 

Glioblastoma multiforme blijft een van de meest agressieve en moeilijkst te behandelen primaire tumoren van het centrale zenuwstelsel. Opkomend bewijs geeft aan dat kanker in de eerste plaats een mitochondriale metabolische ziekte is waarbij tumorcellen afhankelijk worden van fermentatie voor groei. Glucose en glutamine zijn de belangrijkste fermenteerbare brandstoffen die de groei en uitzaaiingen van GBM-cellen stimuleren. Er werd een press-puls therapeutische strategie geïmplementeerd om de beschikbaarheid van glucose en glutamine bij een 38-jarige GBM-patiënt te targeten met behulp van een gemodificeerde standaard behandeling (SOC) en een aangepast Kytogeen dieet (KMT). Aangezien minder dan 20% van de jongere volwassenen in het algemeen langer dan 24 maanden met GBM overleven, is het mogelijk dat de reactie die in dit geval werd waargenomen resulteerde in een deel van KMT en de gemodificeerde SOC. De patiënt is nu 40 jaar oud en blijft in excellente gezondheid zonder merkbare neurologische problemen (Karnofsky Score, 100%) na 24 maanden behandeling.

In het studierapport : 

Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic Metabolic Therapy and Modified Standard of Care: A 24-Month Follow-Up staat nog heel veel meer en wordt tot in detail beschreven hoe de man is behandeld en wat de gevolgen daarvan waren. M.i. echt de moeite waard te lezen. 

Hier het abstract van de studie plus referentielijst.

This is the first report of confirmed GBM treated with a modified SOC together with KMT and HBOT, and other targeted metabolic therapies.

. 2018; 5: 20.
Published online 2018 Mar 29. doi:  [10.3389/fnut.2018.00020]
PMCID: PMC5884883
PMID: 29651419

Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic Metabolic Therapy and Modified Standard of Care: A 24-Month Follow-Up

Abstract

Few advances have been made in overall survival for glioblastoma multiforme (GBM) in more than 40 years. Here, we report the case of a 38-year-old man who presented with chronic headache, nausea, and vomiting accompanied by left partial motor seizures and upper left limb weakness. Enhanced brain magnetic resonance imaging revealed a solid cystic lesion in the right partial space suggesting GBM. Serum testing revealed vitamin D deficiency and elevated levels of insulin and triglycerides. Prior to subtotal tumor resection and standard of care (SOC), the patient conducted a 72-h water-only fast. Following the fast, the patient initiated a vitamin/mineral-supplemented ketogenic diet (KD) for 21 days that delivered 900 kcal/day. In addition to radiotherapy, temozolomide chemotherapy, and the KD (increased to 1,500 kcal/day at day 22), the patient received metformin (1,000 mg/day), methylfolate (1,000 mg/day), chloroquine phosphate (150 mg/day), epigallocatechin gallate (400 mg/day), and hyperbaric oxygen therapy (HBOT) (60 min/session, 5 sessions/week at 2.5 ATA). The patient also received levetiracetam (1,500 mg/day). No steroid medication was given at any time. Post-surgical histology confirmed the diagnosis of GBM. Reduced invasion of tumor cells and thick-walled hyalinized blood vessels were also seen suggesting a therapeutic benefit of pre-surgical metabolic therapy. After 9 months treatment with the modified SOC and complimentary ketogenic metabolic therapy (KMT), the patient’s body weight was reduced by about 19%. Seizures and left limb weakness resolved. Biomarkers showed reduced blood glucose and elevated levels of urinary ketones with evidence of reduced metabolic activity (choline/N-acetylaspartate ratio) and normalized levels of insulin, triglycerides, and vitamin D. This is the first report of confirmed GBM treated with a modified SOC together with KMT and HBOT, and other targeted metabolic therapies. As rapid regression of GBM is rare following subtotal resection and SOC alone, it is possible that the response observed in this case resulted in part from the modified SOC and other novel treatments. Additional studies are needed to validate the efficacy of KMT administered with alternative approaches that selectively increase oxidative stress in tumor cells while restricting their access to glucose and glutamine. The patient remains in excellent health (Karnofsky Score, 100%) with continued evidence of significant tumor regression.

Ethics Statement

This study has been reviewed and approved by the Chair of the faculty of Medicine Alexandria University Medical Research Review Board (metabolic management of GBM patients along with the standard of care therapy, protocol number 69/2016). Following IRB-approved directions for this study, a written informed consent was obtained from the participant for the publication of this case report.

Author Contributions

AE: conceived the study, collected the data, and wrote the paper. MB: conducted surgical procedures related to standard of care. EA: conducted the pathological report. ME: assisted in data collection. MK: provided information on nutritional status and helped write the paper. PM: evaluated data and assisted in manuscript preparation. TS: helped write the manuscript and assisted in data presentation and analysis.

Conflict of Interest Statement

MK was employed by Dietary Therapies LLC. All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

We thank the Foundation for Metabolic Cancer Therapies (Single Cause, Single Cure), CrossFit Inc., the Nelson and Claudia Peltz Foundation, Joseph C. Maroon, the George Yu Foundation, Ellen Davis, Lewis Topper, and the Boston College Research Expense Fund for their support.

Abbreviations

KD-R, calorie restricted ketogenic diet; GFAP, glial fibrillary acidic protein; KMT, ketogenic metabolic therapy; EMA, epithelial membrane antigen; CK, cytokeratin; CD31, cluster of differentiation 31; Ki67, antigen KI-67 also known as Ki-67 or MKI67 is a protein that in humans is encoded by the MKI67 gene; HBOT, hyperbaric oxygen therapy; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; EGCG, epigallocatechin gallate; NAA, N-acetylaspartate; L/P, lactate/pyruvate ratio; IQR, interquartile range; dkl, decaliter; EMK, electronic ketogenic manager; GKI, glucose-ketone index; H&E, haematoxylin and eosin.

References

1. Fisher PG, Buffler PA. Malignant gliomas in 2005: where to GO from here? JAMA (2005) 293:615–7.10.1001/jama.293.5.615 [PubMed] [CrossRef]
2. Krex D, Klink B, Hartmann C, Von Deimling A, Pietsch T, Simon M, et al. Long-term survival with glioblastoma multiforme. Brain (2007) 130:2596–606.10.1093/brain/awm204 [PubMed] [CrossRef]
3. Stupp R, Hegi ME, Mason WP, Van Den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol (2009) 10:459–66.10.1016/S1470-2045(09)70025-7 [PubMed] [CrossRef]
4. Lawrence YR, Blumenthal DT, Matceyevsky D, Kanner AA, Bokstein F, Corn BW. Delayed initiation of radiotherapy for glioblastoma: how important is it to push to the front (or the back) of the line? J Neurooncol (2011) 105:1–7.10.1007/s11060-011-0589-2 [PubMed] [CrossRef]
5. Filippini G, Falcone C, Boiardi A, Broggi G, Bruzzone MG, Caldiroli D, et al. Prognostic factors for survival in 676 consecutive patients with newly diagnosed primary glioblastoma. Neuro Oncol (2008) 10:79–87.10.1215/15228517-2007-038 [PMC free article] [PubMed] [CrossRef]
6. Ahmadloo N, Kani AA, Mohammadianpanah M, Nasrolahi H, Omidvari S, Mosalaei A, et al. Treatment outcome and prognostic factors of adult glioblastoma multiforme. J Egypt Natl Canc Inst (2013) 25:21–30.10.1016/j.jnci.2012.11.001 [PubMed] [CrossRef]
7. Barakat MK, Belal AM, Fadel SH, Gamal H. Outcome of high grade gliomas in limited resource country (10 years’ experience in Alexandria University Oncology Center 2003-2012). J Brain Tumors Neurooncol (2016) 1:1–9.10.4172/2475-3203.1000111 [CrossRef]
8. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, et al. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci U S A (2007) 104:19345–50.10.1073/pnas.0709747104 [PMC free article] [PubMed] [CrossRef]
9. Tanaka K, Sasayama T, Irino Y, Takata K, Nagashima H, Satoh N, et al. Compensatory glutamine metabolism promotes glioblastoma resistance to mTOR inhibitor treatment. J Clin Invest (2015) 125:1591–602.10.1172/JCI78239 [PMC free article] [PubMed] [CrossRef]
10. Seyfried TN, Yu G, Maroon JC, D’agostino DP. Press-pulse: a novel therapeutic strategy for the metabolic management of cancer. Nutr Metab (Lond) (2017) 14:19.10.1186/s12986-017-0178-2 [PMC free article] [PubMed] [CrossRef]
11. Yang L, Venneti S, Nagrath D. Glutaminolysis: a hallmark of cancer metabolism. Annu Rev Biomed Eng (2017) 19:163–94.10.1146/annurev-bioeng-071516-044546 [PubMed] [CrossRef]
12. Rhodes CG, Wise RJ, Gibbs JM, Frackowiak RS, Hatazawa J, Palmer AJ, et al. In vivo disturbance of the oxidative metabolism of glucose in human cerebral gliomas. Ann Neurol (1983) 14:614–26.10.1002/ana.410140604 [PubMed] [CrossRef]
13. Oudard S, Arvelo F, Miccoli L, Apiou F, Dutrillaux AM, Poisson M, et al. High glycolysis in gliomas despite low hexokinase transcription and activity correlated to chromosome 10 loss. Br J Cancer (1996) 74:839–45.10.1038/bjc.1996.446 [PMC free article] [PubMed] [CrossRef]
14. DeBerardinis RJ, Cheng T. Q’s next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene (2010) 29:313–24.10.1038/onc.2009.358 [PMC free article] [PubMed] [CrossRef]
15. Flavahan WA, Wu Q, Hitomi M, Rahim N, Kim Y, Sloan AE, et al. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake. Nat Neurosci (2013) 16:1373–82.10.1038/nn.3510 [PMC free article] [PubMed] [CrossRef]
16. Gatenby RA, Gillies RJ. Glycolysis in cancer: a potential target for therapy. Int J Biochem Cell Biol (2007) 39:1358–66.10.1016/j.biocel.2007.03.021 [PubMed] [CrossRef]
17. Tannahill GM, Curtis AM, Adamik J, Palsson-Mcdermott EM, Mcgettrick AF, Goel G, et al. Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature (2013) 496:238–42.10.1038/nature11986 [PMC free article] [PubMed] [CrossRef]
18. Tretter L, Patocs A, Chinopoulos C. Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis. Biochim Biophys Acta (2016) 1857:1086–101.10.1016/j.bbabio.2016.03.012 [PubMed] [CrossRef]
19. Xu RH, Pelicano H, Zhou Y, Carew JS, Feng L, Bhalla KN, et al. Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res (2005) 65:613–21. [PubMed]
20. Sipe JC, Herman MM, Rubinstein LJ. Electron microscopic observations on human glioblastomas and astrocytomas maintained in organ culture systems. Am J Pathol (1973) 73:589–606. [PMC free article] [PubMed]
21. Scheithauer BW, Bruner JM. The ultrastructural spectrum of astrocytic neoplasms. Ultrastruct Pathol (1987) 11:535–81.10.3109/01913128709048447 [PubMed] [CrossRef]
22. Oudard S, Boitier E, Miccoli L, Rousset S, Dutrillaux B, Poupon MF. Gliomas are driven by glycolysis: putative roles of hexokinase, oxidative phosphorylation and mitochondrial ultrastructure. Anticancer Res (1997) 17:1903–11. [PubMed]
23. Arismendi-Morillo GJ, Castellano-Ramirez AV. Ultrastructural mitochondrial pathology in human astrocytic tumors: potentials implications pro-therapeutics strategies. J Electron Microsc (Tokyo) (2008) 57:33–9.10.1093/jmicro/dfm038 [PubMed] [CrossRef]
24. Katsetos CD, Anni H, Draber P. Mitochondrial dysfunction in gliomas. Semin Pediatr Neurol (2013) 20:216–27.10.1016/j.spen.2013.09.003 [PubMed] [CrossRef]
25. Deighton RF, Le Bihan T, Martin SF, Gerth AM, Mcculloch M, Edgar JM, et al. Interactions among mitochondrial proteins altered in glioblastoma. J Neurooncol (2014) 118:247–56.10.1007/s11060-014-1430-5 [PMC free article] [PubMed] [CrossRef]
26. Feichtinger RG, Weis S, Mayr JA, Zimmermann F, Geilberger R, Sperl W, et al. Alterations of oxidative phosphorylation complexes in astrocytomas. Glia (2014) 62:514–25.10.1002/glia.22621 [PubMed] [CrossRef]
27. Arismendi-Morillo G, Castellano-Ramirez A, Seyfried TN. Ultrastructural characterization of the mitochondria-associated membranes abnormalities in human astrocytomas: functional and therapeutics implications. Ultrastruct Pathol (2017) 41:234–44.10.1080/01913123.2017.1300618 [PubMed] [CrossRef]
28. Seyfried TN, Flores RE, Poff AM, D’agostino DP. Cancer as a metabolic disease: implications for novel therapeutics. Carcinogenesis (2014) 35:515–27.10.1093/carcin/bgt480 [PMC free article] [PubMed] [CrossRef]
29. Chang SM, Parney IF, Huang W, Anderson FA, Jr, Asher AL, Bernstein M, et al. Patterns of care for adults with newly diagnosed malignant glioma. JAMA (2005) 293:557–64.10.1001/jama.293.5.557 [PubMed] [CrossRef]
30. Wong ET, Lok E, Gautam S, Swanson KD. Dexamethasone exerts profound immunologic interference on treatment efficacy for recurrent glioblastoma. Br J Cancer (2015) 113:232–41.10.1038/bjc.2015.238 [PMC free article] [PubMed] [CrossRef]
31. Pitter KL, Tamagno I, Alikhanyan K, Hosni-Ahmed A, Pattwell SS, Donnola S, et al. Corticosteroids compromise survival in glioblastoma. Brain (2016) 139:1458–71.10.1093/brain/aww046 [PMC free article] [PubMed] [CrossRef]
32. Lawrence YR, Wang M, Dicker AP, Andrews D, Curran WJ, Jr, Michalski JM, et al. Early toxicity predicts long-term survival in high-grade glioma. Br J Cancer (2011) 104:1365–71.10.1038/bjc.2011.123 [PMC free article] [PubMed] [CrossRef]
33. Takano T, Lin JH, Arcuino G, Gao Q, Yang J, Nedergaard M. Glutamate release promotes growth of malignant gliomas. Nat Med (2001) 7:1010–5.10.1038/nm0901-1010 [PubMed] [CrossRef]
34. Seyfried TN, Shelton LM, Mukherjee P. Does the existing standard of care increase glioblastoma energy metabolism? Lancet Oncol (2010) 11:811–3.10.1016/S1470-2045(10)70166-2 [PubMed] [CrossRef]
35. Seyfried TN, Flores R, Poff AM, D’agostino DP, Mukherjee P. Metabolic therapy: a new paradigm for managing malignant brain cancer. Cancer Lett (2015) 356:289–300.10.1016/j.canlet.2014.07.015 [PubMed] [CrossRef]
36. Tardito S, Oudin A, Ahmed SU, Fack F, Keunen O, Zheng L, et al. Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma. Nat Cell Biol (2015) 17:1556–68.10.1038/ncb3272 [PMC free article] [PubMed] [CrossRef]
37. Dahlberg D, Struys EA, Jansen EE, Morkrid L, Midttun O, Hassel B. Cyst fluid from cystic, malignant brain tumors: a reservoir of nutrients, including growth factor-like nutrients, for tumor cells. Neurosurgery (2017) 80:917–24.10.1093/neuros/nyw101 [PubMed] [CrossRef]
38. Johnson BE, Mazor T, Hong C, Barnes M, Aihara K, Mclean CY, et al. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science (2014) 343:189–93.10.1126/science.1239947 [PMC free article] [PubMed] [CrossRef]
39. Arcuri C, Tardy M, Rolland B, Armellini R, Menghini AR, Bocchini V. Glutamine synthetase gene expression in a glioblastoma cell-line of clonal origin: regulation by dexamethasone and dibutyryl cyclic AMP. Neurochem Res (1995) 20:1133–9.10.1007/BF00995375 [PubMed] [CrossRef]
40. Klement RJ, Champ CE. Corticosteroids compromise survival in glioblastoma in part through their elevation of blood glucose levels. Brain (2017) 140:e16.10.1093/brain/aww324 [PubMed] [CrossRef]
41. Martuscello RT, Vedam-Mai V, Mccarthy DJ, Schmoll ME, Jundi MA, Louviere CD, et al. A supplemented high-fat low-carbohydrate diet for the treatment of glioblastoma. Clin Cancer Res (2016) 22:2482–95.10.1158/1078-0432.CCR-15-0916 [PubMed] [CrossRef]
42. Winter SF, Loebel F, Dietrich J. Role of ketogenic metabolic therapy in malignant glioma: a systematic review. Crit Rev Oncol Hematol (2017) 112:41–58.10.1016/j.critrevonc.2017.02.016 [PubMed] [CrossRef]
43. Santos JG, Souza Da Cruz WM, Schonthal AH, Salazar MD, Fontes CA, Qiuirico-Santos T, et al. Efficacy of a ketogenic diet with concomitant intranasal perillyl alcohol as a novel strategy for the therapy of recurrent glioblastoma. Oncol Lett (2018) 15:1263–70.10.3892/ol.2017.7362 [PMC free article] [PubMed] [CrossRef]
44. Schwartz KA, Noel M, Nikolai M, Chang HT. Investigating the ketogenic diet as treatment for primary aggressive brain cancer: challenges and lessons learned. Front Nutr (2018) 5:11.10.3389/fnut.2018.00011 [PMC free article] [PubMed] [CrossRef]
45. Fredericks M, Ramsey RB. 3-Oxo acid coenzyme A transferase activity in brain and tumors of the nervous system. J Neurochem (1978) 31:1529–31.10.1111/j.1471-4159.1978.tb06581.x [PubMed] [CrossRef]
46. Zhou W, Mukherjee P, Kiebish MA, Markis WT, Mantis JG, Seyfried TN. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutr Metab (Lond) (2007) 4:5.10.1186/1743-7075-4-5 [PMC free article] [PubMed] [CrossRef]
47. Kiebish MA, Han X, Cheng H, Chuang JH, Seyfried TN. Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer. J Lipid Res (2008) 49:2545–56.10.1194/jlr.M800319-JLR200 [PMC free article] [PubMed] [CrossRef]
48. Maurer GD, Brucker DP, Baehr O, Harter PN, Hattingen E, Walenta S, et al. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy. BMC Cancer (2011) 11:315.10.1186/1471-2407-11-315 [PMC free article] [PubMed] [CrossRef]
49. Chang HT, Olson LK, Schwartz KA. Ketolytic and glycolytic enzymatic expression profiles in malignant gliomas: implication for ketogenic diet therapy. Nutr Metab (2013) 10:47.10.1186/1743-7075-10-47 [PMC free article] [PubMed] [CrossRef]
50. Maroon JC, Seyfried TN, Donohue JP, Bost J. The role of metabolic therapy in treating glioblastoma multiforme. Surg Neurol Int (2015) 6:61.10.4103/2152-7806.155259 [PMC free article] [PubMed] [CrossRef]
51. Mukherjee P, El-Abbadi MM, Kasperzyk JL, Ranes MK, Seyfried TN. Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model. Br J Cancer (2002) 86:1615–21.10.1038/sj.bjc.6600298 [PMC free article] [PubMed] [CrossRef]
52. Mukherjee P, Mulrooney TJ, Marsh J, Blair D, Chiles TC, Seyfried TN. Differential effects of energy stress on AMPK phosphorylation and apoptosis in experimental brain tumor and normal brain. Mol Cancer (2008) 7:37.10.1186/1476-4598-7-37 [PMC free article] [PubMed] [CrossRef]
53. Shelton LM, Huysentruyt LC, Mukherjee P, Seyfried TN. Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse. ASN Neuro (2010) 2:e00038.10.1042/AN20100002 [PMC free article] [PubMed] [CrossRef]
54. Mulrooney TJ, Marsh J, Urits I, Seyfried TN, Mukherjee P. Influence of caloric restriction on constitutive expression of NF-kappaB in an experimental mouse astrocytoma. PLoS One (2011) 6:e18085.10.1371/journal.pone.0018085 [PMC free article] [PubMed] [CrossRef]
55. Iyikesici MS, Slocum AK, Slocum A, Berkarda FB, Kalamian M, Seyfried TN. Efficacy of metabolically supported chemotherapy combined with ketogenic diet, hyperthermia, and hyperbaric oxygen therapy for stage IV triple-negative breast cancer. Cureus (2017) 9:e1445.10.7759/cureus.1445 [PMC free article] [PubMed] [CrossRef]
56. Klement RJ. Beneficial effects of ketogenic diets for cancer patients: a realist review with focus on evidence and confirmation. Med Oncol (2017) 34:132.10.1007/s12032-017-0991-5 [PubMed] [CrossRef]
57. Poff AM, Ari C, Seyfried TN, D’agostino DP. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer. PLoS One (2013) 8:e65522.10.1371/journal.pone.0065522 [PMC free article] [PubMed] [CrossRef]
58. Ye H, Chen M, Cao F, Huang H, Zhan R, Zheng X. Chloroquine, an autophagy inhibitor, potentiates the radiosensitivity of glioma initiating cells by inhibiting autophagy and activating apoptosis. BMC Neurol (2016) 16:178.10.1186/s12883-016-0700-6 [PMC free article] [PubMed] [CrossRef]
59. Yang C, Ko B, Hensley CT, Jiang L, Wasti AT, Kim J, et al. Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol Cell (2014) 56:414–24.10.1016/j.molcel.2014.09.025 [PMC free article] [PubMed] [CrossRef]
60. Meidenbauer JJ, Mukherjee P, Seyfried TN. The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer. Nutr Metab (Lond) (2015) 12:12.10.1186/s12986-015-0009-2 [PMC free article] [PubMed] [CrossRef]
61. Wolf A, Agnihotri S, Guha A. Targeting metabolic remodeling in glioblastoma multiforme. Oncotarget (2010) 1:552–62.10.18632/oncotarget.101014 [PMC free article] [PubMed] [CrossRef]
62. Rockswold SB, Rockswold GL, Zaun DA, Liu J. A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury. J Neurosurg (2013) 118:1317–28.10.3171/2013.2.JNS121468 [PubMed] [CrossRef]
63. Lazaridis C, Andrews CM. Brain tissue oxygenation, lactate-pyruvate ratio, and cerebrovascular pressure reactivity monitoring in severe traumatic brain injury: systematic review and viewpoint. Neurocrit Care (2014) 21:345–55.10.1007/s12028-014-0007-7 [PubMed] [CrossRef]
64. Zuccoli G, Marcello N, Pisanello A, Servadei F, Vaccaro S, Mukherjee P, et al. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: case report. Nutr Metab (Lond) (2010) 7:33.10.1186/1743-7075-7-33 [PMC free article] [PubMed] [CrossRef]
65. Champ CE, Palmer JD, Volek JS, Werner-Wasik M, Andrews DW, Evans JJ, et al. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. J Neurooncol (2014) 117:125–31.10.1007/s11060-014-1362-0 [PubMed] [CrossRef]
66. Rieger J, Bahr O, Maurer GD, Hattingen E, Franz K, Brucker D, et al. ERGO: a pilot study of ketogenic diet in recurrent glioblastoma. Int J Oncol (2014) 44:1843–52.10.3892/ijo.2014.2382 [PMC free article] [PubMed] [CrossRef]
67. Schwartz K, Chang HT, Nikolai M, Pernicone J, Rhee S, Olson K, et al. Treatment of glioma patients with ketogenic diets: report of two cases treated with an IRB-approved energy-restricted ketogenic diet protocol and review of the literature. Cancer Metab (2015) 3:3.10.1186/s40170-015-0129-1 [PMC free article] [PubMed] [CrossRef]
68. Woolf EC, Syed N, Scheck AC. Tumor metabolism, the ketogenic diet and beta-hydroxybutyrate: novel approaches to adjuvant brain tumor therapy. Front Mol Neurosci (2016) 9:122.10.3389/fnmol.2016.00122 [PMC free article] [PubMed] [CrossRef]
69. Artzi M, Liberman G, Vaisman N, Bokstein F, Vitinshtein F, Aizenstein O, et al. Changes in cerebral metabolism during ketogenic diet in patients with primary brain tumors: 1H-MRS study. J Neurooncol (2017) 132:267–75.10.1007/s11060-016-2364-x [PubMed] [CrossRef]
70. Nebeling LC, Miraldi F, Shurin SB, Lerner E. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr (1995) 14:202–8.10.1080/07315724.1995.10718495 [PubMed] [CrossRef]
71. Seyfried TN, Sanderson TM, El-Abbadi MM, Mcgowan R, Mukherjee P. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Br J Cancer (2003) 89:1375–82.10.1038/sj.bjc.6601269 [PMC free article] [PubMed] [CrossRef]
72. McGirt MJ, Chaichana KL, Gathinji M, Attenello F, Than K, Ruiz AJ, et al. Persistent outpatient hyperglycemia is independently associated with decreased survival after primary resection of malignant brain astrocytomas. Neurosurgery (2008) 63:286–91; discussion 291.10.1227/01.NEU.0000315282.61035.48 [PubMed] [CrossRef]
73. Derr RL, Ye X, Islas MU, Desideri S, Saudek CD, Grossman SA. Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma. J Clin Oncol (2009) 27:1082–6.10.1200/JCO.2008.19.1098 [PMC free article] [PubMed] [CrossRef]
74. Mayer A, Vaupel P, Struss HG, Giese A, Stockinger M, Schmidberger H. Strong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme. Strahlenther Onkol (2014) 190:933–8.10.1007/s00066-014-0696-z [PubMed] [CrossRef]
75. Tieu MT, Lovblom LE, Mcnamara MG, Mason W, Laperriere N, Millar BA, et al. Impact of glycemia on survival of glioblastoma patients treated with radiation and temozolomide. J Neurooncol (2015) 124:119–26.10.1007/s11060-015-1815-0 [PMC free article] [PubMed] [CrossRef]
76. Zhao S, Cai J, Li J, Bao G, Li D, Li Y, et al. Bioinformatic profiling identifies a glucose-related risk signature for the malignancy of glioma and the survival of patients. Mol Neurobiol (2016) 54:8203–10.10.1007/s12035-016-0314-4 [PubMed] [CrossRef]
77. Arismendi-Morillo G. Electron microscopy morphology of the mitochondrial network in gliomas and their vascular microenvironment. Biochim Biophys Acta (2011) 1807:602–8.10.1016/j.bbabio.2010.11.001 [PubMed] [CrossRef]
78. Marsh J, Mukherjee P, Seyfried TN. Akt-dependent proapoptotic effects of dietary restriction on late-stage management of a phosphatase and tensin homologue/tuberous sclerosis complex 2-deficient mouse astrocytoma. Clin Cancer Res (2008) 14:7751–62.10.1158/1078-0432.CCR-08-0213 [PubMed] [CrossRef]
79. Jiang YS, Wang FR. Caloric restriction reduces edema and prolongs survival in a mouse glioma model. J Neurooncol (2013) 114:25–32.10.1007/s11060-013-1154-y [PubMed] [CrossRef]
80. Newsholme P, Lima MM, Procopio J, Pithon-Curi TC, Doi SQ, Bazotte RB, et al. Glutamine and glutamate as vital metabolites. Braz J Med Biol Res (2003) 36:153–63.10.1590/S0100-879X2003000200002 [PubMed] [CrossRef]
81. Yang C, Sudderth J, Dang T, Bachoo RG, Mcdonald JG, Deberardinis RJ. Glioblastoma cells require glutamate dehydrogenase to survive impairments of glucose metabolism or Akt signaling. Cancer Res (2009) 69:7986–93.10.1158/0008-5472.CAN-09-2266 [PMC free article] [PubMed] [CrossRef]
82. Stehle G, Sinn H, Wunder A, Schrenk HH, Stewart JC, Hartung G, et al. Plasma protein (albumin) catabolism by the tumor itself – implications for tumor metabolism and the genesis of cachexia. Crit Rev Oncol Hematol (1997) 26:77–100.10.1016/S1040-8428(97)00015-2 [PubMed] [CrossRef]
83. Seyfried TN, Mukherjee P. Targeting energy metabolism in brain cancer: review and hypothesis. Nutr Metab (Lond) (2005) 2:30.10.1186/1743-7075-2-30 [PMC free article] [PubMed] [CrossRef]
84. Seyfried TN. Nothing in cancer biology makes sense except in the light of evolution. Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer. Hoboken, NJ: John Wiley & Sons; (2012). p. 261–75.
85. Horska A, Barker PB. Imaging of brain tumors: MR spectroscopy and metabolic imaging. Neuroimaging Clin N Am (2010) 20:293–310.10.1016/j.nic.2010.04.003 [PMC free article] [PubMed] [CrossRef]
86. Chaumeil MM, Radoul M, Najac C, Eriksson P, Viswanath P, Blough MD, et al. Hyperpolarized (13)C MR imaging detects no lactate production in mutant IDH1 gliomas: implications for diagnosis and response monitoring. Neuroimage Clin (2016) 12:180–9.10.1016/j.nicl.2016.06.018 [PMC free article] [PubMed] [CrossRef]

Articles from Frontiers in Nutrition are provided here courtesy of Frontiers Media SA

Plaats een reactie ...

Reageer op "Hersentumoren: man (38 jaar) blijft na operatie al ruim twee jaar zonder recidief van een glioblastoma door standaard behandeling van bestraling en temodal met aanvullend onder begeleiding een kytogeen dieet en aanvullende vitamines."


Gerelateerde artikelen
 

Gerelateerde artikelen

Video-film (Nederlands): Zo >> Documentaire over drie kankerpatiënten >> Radio interview met Ian Gawler >> Alvleesklierkanker: ervaringsverhaal >> Alvleesklierkanker: ervaringsverhaal >> Baarmoederhalskanker: ervaringsverhaal >> Blaaskanker: ervaringsverhaal >> Blaaskanker: ervaringsverhaal >> Borstkanker: Judy Perkins >> Borstkanker: Ervaringsverhaal >>