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Published in: BMC Neurology 1/2023

Open Access 01-12-2023 | Glioblastoma | Research

Antisecretory factor is safe to use as add-on treatment in newly diagnosed glioblastoma

Authors: Erik Ehinger, Jan Kopecky, Anna Darabi, Edward Visse, Charlotte Edvardsson, Gregor Tomasevic, David Cederberg, Mattias Belting, Johan Bengzon, Peter Siesjö

Published in: BMC Neurology | Issue 1/2023

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Abstract

Purpose

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite the best available treatment, prognosis remains poor. Current standard therapy consists of surgical removal of the tumor followed by radiotherapy and chemotherapy with the alkylating agent temozolomide (TMZ). Experimental studies suggest that antisecretory factor (AF), an endogenous protein with proposed antisecretory and anti-inflammatory properties, may potentiate the effect of TMZ and alleviate cerebral edema. Salovum is an egg yolk powder enriched for AF and is classified as a medical food in the European Union. In this pilot study, we evaluate the safety and feasibility of add-on Salovum in GBM patients.

Methods

Eight patients with newly diagnosed, histologically confirmed GBM were prescribed Salovum during concomitant radiochemotherapy. Safety was determined by the number of treatment-related adverse events. Feasibility was determined by the number of patients who completed the full prescribed Salovum treatment.

Results

No serious treatment-related adverse events were observed. Out of 8 included patients, 2 did not complete the full treatment. Only one of the dropouts was due to issues directly related to Salovum, which were nausea and loss of appetite. Median survival was 23 months.

Conclusions

We conclude that Salovum is safe to use as an add-on treatment for GBM. In terms of feasibility, adherence to the treatment regimen requires a determined and independent patient as the large doses prescribed may cause nausea and loss of appetite.

Trial registration

ClinicalTrials.​gov NCT04116138. Registered on 04/10/2019.
Appendix
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Literature
1.
go back to reference Dressler EV, et al. Patterns and disparities of care in glioblastoma. Neurooncol Pract. 2019;6(1):37–46.PubMed Dressler EV, et al. Patterns and disparities of care in glioblastoma. Neurooncol Pract. 2019;6(1):37–46.PubMed
2.
go back to reference Bush NA, Chang SM, Berger MS. Current and future strategies for treatment of glioma. Neurosurg Rev. 2017;40(1):1–14.CrossRefPubMed Bush NA, Chang SM, Berger MS. Current and future strategies for treatment of glioma. Neurosurg Rev. 2017;40(1):1–14.CrossRefPubMed
3.
go back to reference Stupp R, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.CrossRefPubMed Stupp R, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.CrossRefPubMed
4.
go back to reference Qazi MA, et al. Intratumoral heterogeneity: pathways to treatment resistance and relapse in human glioblastoma. Ann Oncol. 2017;28(7):1448–56.CrossRefPubMed Qazi MA, et al. Intratumoral heterogeneity: pathways to treatment resistance and relapse in human glioblastoma. Ann Oncol. 2017;28(7):1448–56.CrossRefPubMed
5.
go back to reference Ou A, Yung WKA, Majd N. Molecular mechanisms of treatment resistance in glioblastoma. Int J Mol Sci. 2020;22(1):351. Ou A, Yung WKA, Majd N. Molecular mechanisms of treatment resistance in glioblastoma. Int J Mol Sci. 2020;22(1):351.
6.
go back to reference Heldin CH, et al. High interstitial fluid pressure - an obstacle in cancer therapy. Nat Rev Cancer. 2004;4(10):806–13.CrossRefPubMed Heldin CH, et al. High interstitial fluid pressure - an obstacle in cancer therapy. Nat Rev Cancer. 2004;4(10):806–13.CrossRefPubMed
7.
go back to reference Persson AI, et al. High interstitial fluid pressure regulates tumor growth and drug uptake in human glioblastoma. Neuro Oncol. 2014;16(suppl_3):iii32.CrossRefPubMedCentral Persson AI, et al. High interstitial fluid pressure regulates tumor growth and drug uptake in human glioblastoma. Neuro Oncol. 2014;16(suppl_3):iii32.CrossRefPubMedCentral
8.
go back to reference Ulgheri C, Paganini B, Rossi F. Antisecretory factor as a potential health-promoting molecule in man and animals. Nutr Res Rev. 2010;23(2):300–13.CrossRefPubMed Ulgheri C, Paganini B, Rossi F. Antisecretory factor as a potential health-promoting molecule in man and animals. Nutr Res Rev. 2010;23(2):300–13.CrossRefPubMed
9.
go back to reference Björck S, et al. Food induced stimulation of the antisecretory factor can improve symptoms in human inflammatory bowel disease: a study of a concept. Gut. 2000;46(6):824–9.CrossRefPubMedPubMedCentral Björck S, et al. Food induced stimulation of the antisecretory factor can improve symptoms in human inflammatory bowel disease: a study of a concept. Gut. 2000;46(6):824–9.CrossRefPubMedPubMedCentral
10.
go back to reference Kaya I, et al. Antisecretory factor (AF) egg-yolk peptides reflects the intake of AF-activating feed in hens. Clin Nutr Experimental. 2017;12:27–36.CrossRef Kaya I, et al. Antisecretory factor (AF) egg-yolk peptides reflects the intake of AF-activating feed in hens. Clin Nutr Experimental. 2017;12:27–36.CrossRef
11.
go back to reference Zaman S, et al. Antisecretory factor effectively and safely stops childhood diarrhoea: a placebo-controlled, randomised study. Acta Paediatr. 2014;103(6):659–64.CrossRefPubMed Zaman S, et al. Antisecretory factor effectively and safely stops childhood diarrhoea: a placebo-controlled, randomised study. Acta Paediatr. 2014;103(6):659–64.CrossRefPubMed
12.
go back to reference Zaman S, et al. B 221, a medical food containing antisecretory factor reduces child diarrhoea: a placebo controlled trial. Acta Paediatr. 2007;96(11):1655–9.CrossRefPubMed Zaman S, et al. B 221, a medical food containing antisecretory factor reduces child diarrhoea: a placebo controlled trial. Acta Paediatr. 2007;96(11):1655–9.CrossRefPubMed
13.
go back to reference Zaman S, et al. High doses of Antisecretory factor stop diarrhea fast without recurrence for six weeks post treatment. Int J Infect Dis. 2018;71:48–52.CrossRefPubMed Zaman S, et al. High doses of Antisecretory factor stop diarrhea fast without recurrence for six weeks post treatment. Int J Infect Dis. 2018;71:48–52.CrossRefPubMed
14.
go back to reference Eriksson A, et al. Antisecretory factor-induced regression of Crohn's disease in a weak responder to conventional pharmacological treatment. Inflamm Bowel Dis. 2003;9(6):398–400.CrossRefPubMed Eriksson A, et al. Antisecretory factor-induced regression of Crohn's disease in a weak responder to conventional pharmacological treatment. Inflamm Bowel Dis. 2003;9(6):398–400.CrossRefPubMed
15.
go back to reference Eriksson A, et al. Effect of antisecretory factor in ulcerative colitis on histological and laborative outcome: a short period clinical trial. Scand J Gastroenterol. 2003;38(10):1045–9.CrossRefPubMed Eriksson A, et al. Effect of antisecretory factor in ulcerative colitis on histological and laborative outcome: a short period clinical trial. Scand J Gastroenterol. 2003;38(10):1045–9.CrossRefPubMed
16.
go back to reference Leong SC, Narayan S, Lesser TH. Antisecretory factor-inducing therapy improves patient-reported functional levels in Meniere's disease. Ann Otol Rhinol Laryngol. 2013;122(10):619–24.CrossRefPubMed Leong SC, Narayan S, Lesser TH. Antisecretory factor-inducing therapy improves patient-reported functional levels in Meniere's disease. Ann Otol Rhinol Laryngol. 2013;122(10):619–24.CrossRefPubMed
17.
go back to reference Hanner P, et al. Antisecretory factor-inducing therapy improves the clinical outcome in patients with Ménière’s disease. Acta Otolaryngol. 2010;130(2):223–7.CrossRefPubMed Hanner P, et al. Antisecretory factor-inducing therapy improves the clinical outcome in patients with Ménière’s disease. Acta Otolaryngol. 2010;130(2):223–7.CrossRefPubMed
18.
go back to reference Ingvardsen CJ, Klokker M. Antisecretory therapy with no improvement in functional level in Meniere's disease. Acta Otolaryngol. 2016;136(3):232–5.CrossRefPubMed Ingvardsen CJ, Klokker M. Antisecretory therapy with no improvement in functional level in Meniere's disease. Acta Otolaryngol. 2016;136(3):232–5.CrossRefPubMed
19.
go back to reference Scarpa A, et al. Food-induced stimulation of the antisecretory factor to improve symptoms in Meniere's disease: our results. Eur Arch Otorhinolaryngol. 2020;277(1):77–83.CrossRefPubMed Scarpa A, et al. Food-induced stimulation of the antisecretory factor to improve symptoms in Meniere's disease: our results. Eur Arch Otorhinolaryngol. 2020;277(1):77–83.CrossRefPubMed
20.
go back to reference Hanner P, et al. Increased antisecretory factor reduces vertigo in patients with Ménière’s disease: a pilot study. Hear Res. 2004;190(1):31–6.CrossRefPubMed Hanner P, et al. Increased antisecretory factor reduces vertigo in patients with Ménière’s disease: a pilot study. Hear Res. 2004;190(1):31–6.CrossRefPubMed
22.
go back to reference Gatzinsky K, et al. Elevated intracranial pressure after head trauma can be suppressed by antisecretory factor-a pilot study. Acta Neurochir. 2020;162(7):1629–37.CrossRefPubMed Gatzinsky K, et al. Elevated intracranial pressure after head trauma can be suppressed by antisecretory factor-a pilot study. Acta Neurochir. 2020;162(7):1629–37.CrossRefPubMed
23.
go back to reference Nur HA, et al. Salovum egg yolk containing Antisecretory factor as an adjunct therapy in severe cholera in adult males: a pilot study. J Health Popul Nutr. 2011;29(4):297. Nur HA, et al. Salovum egg yolk containing Antisecretory factor as an adjunct therapy in severe cholera in adult males: a pilot study. J Health Popul Nutr. 2011;29(4):297.
24.
go back to reference Al-Olama M, et al. The peptide AF-16 decreases high interstitial fluid pressure in solid tumors. Acta Oncol. 2011;50(7):1098–104.CrossRefPubMed Al-Olama M, et al. The peptide AF-16 decreases high interstitial fluid pressure in solid tumors. Acta Oncol. 2011;50(7):1098–104.CrossRefPubMed
25.
go back to reference Ilkhanizadeh S, et al. Antisecretory factor-mediated inhibition of cell volume dynamics produces antitumor activity in glioblastoma. Mol Cancer Res. 2018;16(5):777–90.CrossRefPubMedPubMedCentral Ilkhanizadeh S, et al. Antisecretory factor-mediated inhibition of cell volume dynamics produces antitumor activity in glioblastoma. Mol Cancer Res. 2018;16(5):777–90.CrossRefPubMedPubMedCentral
26.
go back to reference Kopecky J, et al. Intratumoral administration of the antisecretory peptide AF16 cures murine gliomas and modulates macrophage functions. Sci Rep. 2022;12(1):4609.CrossRefPubMedPubMedCentral Kopecky J, et al. Intratumoral administration of the antisecretory peptide AF16 cures murine gliomas and modulates macrophage functions. Sci Rep. 2022;12(1):4609.CrossRefPubMedPubMedCentral
28.
go back to reference Luedi MM, et al. A dexamethasone-regulated gene signature is prognostic for poor survival in glioblastoma patients. J Neurosurg Anesthesiol. 2017;29(1):46–58.CrossRefPubMedPubMedCentral Luedi MM, et al. A dexamethasone-regulated gene signature is prognostic for poor survival in glioblastoma patients. J Neurosurg Anesthesiol. 2017;29(1):46–58.CrossRefPubMedPubMedCentral
29.
go back to reference Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.CrossRefPubMed Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.CrossRefPubMed
30.
go back to reference Oken MM, et al. Toxicity and response criteria of the eastern cooperative oncology group. Am J Clin Oncol. 1982;5(6):649–55.CrossRefPubMed Oken MM, et al. Toxicity and response criteria of the eastern cooperative oncology group. Am J Clin Oncol. 1982;5(6):649–55.CrossRefPubMed
32.
go back to reference Skaga E, et al. Real-world validity of randomized controlled phase III trials in newly diagnosed glioblastoma: to whom do the results of the trials apply? Neurooncol Adv. 2021;3(1):vdab008.PubMedPubMedCentral Skaga E, et al. Real-world validity of randomized controlled phase III trials in newly diagnosed glioblastoma: to whom do the results of the trials apply? Neurooncol Adv. 2021;3(1):vdab008.PubMedPubMedCentral
33.
go back to reference Hegi ME, et al. MGMT gene silencing and benefit from Temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997–1003.CrossRefPubMed Hegi ME, et al. MGMT gene silencing and benefit from Temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997–1003.CrossRefPubMed
34.
go back to reference Weller M, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2021;18(3):170–86.CrossRefPubMed Weller M, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2021;18(3):170–86.CrossRefPubMed
35.
go back to reference Hui CY, et al. Impact of overall corticosteroid exposure during chemoradiotherapy on lymphopenia and survival of glioblastoma patients. J Neuro-Oncol. 2019;143(1):129–36.CrossRef Hui CY, et al. Impact of overall corticosteroid exposure during chemoradiotherapy on lymphopenia and survival of glioblastoma patients. J Neuro-Oncol. 2019;143(1):129–36.CrossRef
36.
go back to reference Lange S, Lönnroth I. The antisecretory factor: synthesis, anatomical and cellular distribution, and biological action in experimental and clinical studies, in International review of cytology: Academic Press; 2001. p. 39–75. Lange S, Lönnroth I. The antisecretory factor: synthesis, anatomical and cellular distribution, and biological action in experimental and clinical studies, in International review of cytology: Academic Press; 2001. p. 39–75.
37.
go back to reference Davidson TS, Hickey WF. Distribution and immunoregulatory properties of antisecretory factor. Lab Investig. 2004;84(3):307–19.CrossRefPubMed Davidson TS, Hickey WF. Distribution and immunoregulatory properties of antisecretory factor. Lab Investig. 2004;84(3):307–19.CrossRefPubMed
38.
go back to reference Interaction of proteasomes and complement C3, assay of Antisecretory factor in blood. J Immunoassay Immunochem. 2016;37(1):43-54. Interaction of proteasomes and complement C3, assay of Antisecretory factor in blood. J Immunoassay Immunochem. 2016;37(1):43-54.
Metadata
Title
Antisecretory factor is safe to use as add-on treatment in newly diagnosed glioblastoma
Authors
Erik Ehinger
Jan Kopecky
Anna Darabi
Edward Visse
Charlotte Edvardsson
Gregor Tomasevic
David Cederberg
Mattias Belting
Johan Bengzon
Peter Siesjö
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2023
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-023-03119-4

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