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Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse.

Shelton LM, Huysentruyt LC, Mukherjee P, Seyfried TN - ASN Neuro (2010)

Bottom Line: GBM (glioblastoma multiforme) is the most aggressive and invasive form of primary human brain cancer.Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction) for its ability to reduce tumour size and invasion.In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

View Article: PubMed Central - PubMed

Affiliation: Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, U.S.A.

ABSTRACT
GBM (glioblastoma multiforme) is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction) for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12-15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

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Study design and influence of CR on body weights and plasma glucose levels(A) VM mice were implanted with VM-M3/Fluc tumour fragments as described in the Material and methods section and were given a 60% CR starting on days 4–6. Brains were removed 12–15 days post-implantation and imaged ex vivo. (B) The body weights of the VM mice were monitored daily. Values represent the means±S.E.M. for 9–10 mice per group. VM mice were sacrificed and plasma was collected for the analysis of glucose (C) and ketones (D) as described in the Materials and methods section. Values represent the means±S.E.M. The * indicates that the CR values differ significantly from those of the AL control group at P<0.05 using the two-tailed Student's t test.
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Figure 1: Study design and influence of CR on body weights and plasma glucose levels(A) VM mice were implanted with VM-M3/Fluc tumour fragments as described in the Material and methods section and were given a 60% CR starting on days 4–6. Brains were removed 12–15 days post-implantation and imaged ex vivo. (B) The body weights of the VM mice were monitored daily. Values represent the means±S.E.M. for 9–10 mice per group. VM mice were sacrificed and plasma was collected for the analysis of glucose (C) and ketones (D) as described in the Materials and methods section. Values represent the means±S.E.M. The * indicates that the CR values differ significantly from those of the AL control group at P<0.05 using the two-tailed Student's t test.

Mentions: Adult male and female VM mice (approx. 60–90 days old) were individually housed 1–2 days prior to tumour cell implantation. Mice were kept in filter-topped plastic cages containing Sani-Chip bedding (P.J. Murphy Forest Products Corporation). Body weight and food intake was recorded daily and standard chow was provided AL. Tumour fragments were implanted on day zero (Figure 1A). The mice were then matched for body weight and separated into two groups (AL and CR) 4–6 days post-implantation. Imaging confirmed the presence of a growing tumour in each implanted mouse. Mice were administered the standard chow diet either AL or restricted to 40% of their normal food intake (60% restriction) at approx. the same time (10:00 hours) each day. All mice were weighed daily prior to food administration. Mice were sacrificed at the time of morbidity, which was approx. 12–15 day post-implantation for the control AL mice (Figure 1A).


Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse.

Shelton LM, Huysentruyt LC, Mukherjee P, Seyfried TN - ASN Neuro (2010)

Study design and influence of CR on body weights and plasma glucose levels(A) VM mice were implanted with VM-M3/Fluc tumour fragments as described in the Material and methods section and were given a 60% CR starting on days 4–6. Brains were removed 12–15 days post-implantation and imaged ex vivo. (B) The body weights of the VM mice were monitored daily. Values represent the means±S.E.M. for 9–10 mice per group. VM mice were sacrificed and plasma was collected for the analysis of glucose (C) and ketones (D) as described in the Materials and methods section. Values represent the means±S.E.M. The * indicates that the CR values differ significantly from those of the AL control group at P<0.05 using the two-tailed Student's t test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2908744&req=5

Figure 1: Study design and influence of CR on body weights and plasma glucose levels(A) VM mice were implanted with VM-M3/Fluc tumour fragments as described in the Material and methods section and were given a 60% CR starting on days 4–6. Brains were removed 12–15 days post-implantation and imaged ex vivo. (B) The body weights of the VM mice were monitored daily. Values represent the means±S.E.M. for 9–10 mice per group. VM mice were sacrificed and plasma was collected for the analysis of glucose (C) and ketones (D) as described in the Materials and methods section. Values represent the means±S.E.M. The * indicates that the CR values differ significantly from those of the AL control group at P<0.05 using the two-tailed Student's t test.
Mentions: Adult male and female VM mice (approx. 60–90 days old) were individually housed 1–2 days prior to tumour cell implantation. Mice were kept in filter-topped plastic cages containing Sani-Chip bedding (P.J. Murphy Forest Products Corporation). Body weight and food intake was recorded daily and standard chow was provided AL. Tumour fragments were implanted on day zero (Figure 1A). The mice were then matched for body weight and separated into two groups (AL and CR) 4–6 days post-implantation. Imaging confirmed the presence of a growing tumour in each implanted mouse. Mice were administered the standard chow diet either AL or restricted to 40% of their normal food intake (60% restriction) at approx. the same time (10:00 hours) each day. All mice were weighed daily prior to food administration. Mice were sacrificed at the time of morbidity, which was approx. 12–15 day post-implantation for the control AL mice (Figure 1A).

Bottom Line: GBM (glioblastoma multiforme) is the most aggressive and invasive form of primary human brain cancer.Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction) for its ability to reduce tumour size and invasion.In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

View Article: PubMed Central - PubMed

Affiliation: Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, U.S.A.

ABSTRACT
GBM (glioblastoma multiforme) is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction) for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12-15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

Show MeSH
Related in: MedlinePlus