PMC4371612_01
Immunohistochemistry staining for ketolytic enzymes BDH-1 and OXCT-1. (A-C) Micrographs of patient no. 1's tumor. (A) H&E stained section. (B) Immunohistochemistry reaction shows that most cells in this region, probably tumor cells, demonstrate decreased or 'low' expression of OXCT-1. (C) Many cells in this same region appear positive for BDH-1. (D-F) Micrographs of patient no. 2's tumor. (D) H&E stained section. (E) Immunohistochemistry reaction shows that most tumor cells in this region are positive for OXCT-1. (F) Most tumor cells in the same region also appear positive for BDH-1. All micrographs were taken at the same magnification (x200).
40170_2015_129_Fig2_HTML.jpg
PMC4371612_02_40170_2015_129_Fig2_HTML.jpg
Fig2
However, evaluation of his subsequent biopsy showed positive expression of BDH-1 (Figure 2C). The tumor of patient no. 2 was positive for both BDH-1 and OXCT-1 (Figure 2E,F).
Blood glucose, ketones, and daily weights. Twice daily body weights (A, B), blood glucose (C, D) and ketones (E, F) are graphed for each day the patient was treated with ERKD. Data for patient no. 1 is depicted in the panels (A, C, E) to the left and patient no. 2 in the panels (B, D, F) to the right.
40170_2015_129_Fig3_HTML.jpg
PMC4371612_02_40170_2015_129_Fig3_HTML.jpg
Fig3
His blood glucose levels could not be maintained below the target value of 80 mg/dl but with a few exceptions remained below 100 mg/dl (Figure 3).
MRI and PET imaging studies. (A,
B) MRI post-contrast T1-weighted images of patient no. 1 showing a right occipital single mass before ERKD (A) and a second left occipital mass after ERKD (B). (C-F) FDG PET brain images of patient no. 2: (C) and (E) were done at the beginning of the ERKD protocol. (D) and (F) are images taken 12 weeks after the initiation of ERKD protocol. These show an area of new disease in the left frontal lobe (D) and an area of progressed disease in the left occipital lobe (F).
40170_2015_129_Fig4_HTML.jpg
PMC4371612_01_40170_2015_129_Fig4_HTML.jpg
Fig4
AM >2 mM (Figure 3), but his AM and PM blood glucose increased to >80 mg/dl most of the time (61% of time) (Figure 3). After 4 weeks of treatment with the ERKD, patient 1 withdrew from the study due to further impairment of vision, mobility and cognition, and magnetic resonance imaging (MRI)-demonstrated tumor growth (Figure 4A,B).
PMC4371612_02
Schematic overview of the ERKD protocol. After standard therapies, patients are evaluated with history and physical examination and a PET/CT scan of the brain. These evaluations are repeated after 6 and 12 weeks of diet treatment. After 12 weeks of ERKD therapy, the protocol is completed.
40170_2015_129_Fig1_HTML.jpg
PMC4371612_02_40170_2015_129_Fig1_HTML.jpg
Fig1
Both of these patients (no. 1 and no. 2) who were treated with an ERKD protocol (Figure 1) had progression of their disease.
Immunohistochemistry staining for ketolytic enzymes BDH-1 and OXCT-1. (A-C) Micrographs of patient no. 1's tumor. (A) H&E stained section. (B) Immunohistochemistry reaction shows that most cells in this region, probably tumor cells, demonstrate decreased or 'low' expression of OXCT-1. (C) Many cells in this same region appear positive for BDH-1. (D-F) Micrographs of patient no. 2's tumor. (D) H&E stained section. (E) Immunohistochemistry reaction shows that most tumor cells in this region are positive for OXCT-1. (F) Most tumor cells in the same region also appear positive for BDH-1. All micrographs were taken at the same magnification (x200).
40170_2015_129_Fig2_HTML.jpg
PMC4371612_02_40170_2015_129_Fig2_HTML.jpg
Fig2
However, evaluation of his subsequent biopsy showed positive expression of BDH-1 (Figure 2C). The tumor of patient no. 2 was positive for both BDH-1 and OXCT-1 (Figure 2E,F).
Blood glucose, ketones, and daily weights. Twice daily body weights (A, B), blood glucose (C, D) and ketones (E, F) are graphed for each day the patient was treated with ERKD. Data for patient no. 1 is depicted in the panels (A, C, E) to the left and patient no. 2 in the panels (B, D, F) to the right.
40170_2015_129_Fig3_HTML.jpg
PMC4371612_02_40170_2015_129_Fig3_HTML.jpg
Fig3
His blood glucose levels could not be maintained below the target value of 80 mg/dl but with a few exceptions remained below 100 mg/dl (Figure 3).
PMC4371612_03