title: Caloric restriction reduces edema and prolongs survival in a mouse glioma model.
abstract: Regardless of their cell type of origin, all aggressive brain tumors, such as malignant gliomas and metastatic tumors produce brain edema, which is an important cause of patient morbidity and mortality. Caloric restriction (CR) has long been recognized as a natural therapy that improves health, promotes longevity, and significantly reduces both the incidence and growth of many tumor types. The aim of present work was to investigate the effect of CR on edema and survival in the mice implanted with U87 gliomas. We found that CR significantly inhibited the intracerebral tumor growth, attenuated brain edema, and ultimately prolonged survival of mice with U87 gliomas. Plasma corticosterone level was found higher and serum VEGF and IGF-1 levels were found lower in CR, when compared to AL group. CR upregulated tight junction proteins including claudin-1, claudin-5 and ZO-1, downregulated VEGF and VEGFR2, enhanced α-SMA expression, and reduced AQP1 expression in U87 gliomas. In addition, CR suppressed inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) formation in U87 gliomas. In conclusion, CR attenuated edema in U87 orthotopic mouse glioma model associated with elevation of corticosterone, suppression of VEGF/VEGFR2, improvement of tight junctions, and suppression of iNOS expression and NO formation. Our results suggested that CR might be an effective therapy for recurrent malignant brain cancers through alleviating associated edema.
authors.affiliation: Center of Tumor, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Jiang
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Wang
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D001929:Brain Edema / Q000209:etiology*; D001932:Brain Neoplasms / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy; D031204:Caloric Restriction / Q000379:methods*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005910:Glioma / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy; D005947:Glucose / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood; D008297:Male; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D010539:Permeability; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D009566:Nitrates; D062725:Tight Junction Proteins; D042461:Vascular Endothelial Growth Factor A; D019344:Lactic Acid; D007334:Insulin-Like Growth Factor I; D005947:Glucose; D020155:3-Hydroxybutyric Acid