TY - JOUR
T1 - Amino acid metabolism and inflammatory burden in ovarian cancer patients undergoing intense oncological therapy
AU - Dillon, E. L.
AU - Volpi, Elena
AU - Wolfe, Robert R.
AU - Sinha, Sandeep
AU - Sanford, Arthur P.
AU - Arrastia, Concepcion D.
AU - Urban, Randall J.
AU - Casperson, Shanon L.
AU - Paddon-Jones, Douglas
AU - Sheffield-Moore, Melinda
N1 - Funding Information:
This research was funded by NIH/NIA Claude D. Pepper Older Americans Independence Center Grant # P60 AG17231 (to J.S. Goodwin and R.R. Wolfe) and R01 AG21539 (M. Sheffield-Moore). Studies were conducted on the GCRC at UTMB and funded by Grant M01 RR 00073 from the National Center for Research Resources, NIH, USPHS.
PY - 2007/12
Y1 - 2007/12
N2 - Background & aims: Cancer and oncological therapy are associated with a progressive physical deterioration, malnutrition, and enhanced inflammatory burden. Our considerable data showing the strong anabolic potential of amino acids (AA) led us to test whether AA can acutely stimulate muscle protein synthesis in cancer patients (CA) undergoing intense chemotherapy. Methods: Mixed muscle fractional synthesis rate (FSR), rates of phenylalanine appearance and disappearance (Ra and Rd), and net phenylalanine balance (NB) were measured during a primed constant infusion of l-[ring-2H5]phenylalanine. Blood and muscle tissue samples were collected in the basal state and following ingestion of 40 g of AA given in 30 mL boluses every 10 min for 3 h. Serum and tissue cytokines and NF-κB expression in skeletal muscle were measured and compared to normative, healthy older controls (OC). Results: Skeletal muscle TNF-α, IL-6, and NF-κB were elevated in CA. FSR and model-derived protein synthesis (Rd) increased significantly from basal to AA (FSR: 0.052±0.009 vs. 0.120±0.008% h-1, P<0.001; Rd: 23.1±4.1 vs. 36.4±5.0 nmol min-1 100 mL leg-1, P≤0.05). Model-derived protein breakdown (Ra) remained unchanged from basal to AA. Phenylalanine NB improved from a negative basal value (-16±2) to zero (0.8±6 nmol min-1 100 ml leg-1, P≤0.05) following AA. Conclusion: Despite advanced cancer, ongoing therapy, and an enhanced inflammatory burden, AA were capable of acutely stimulating muscle protein synthesis in these patients.
AB - Background & aims: Cancer and oncological therapy are associated with a progressive physical deterioration, malnutrition, and enhanced inflammatory burden. Our considerable data showing the strong anabolic potential of amino acids (AA) led us to test whether AA can acutely stimulate muscle protein synthesis in cancer patients (CA) undergoing intense chemotherapy. Methods: Mixed muscle fractional synthesis rate (FSR), rates of phenylalanine appearance and disappearance (Ra and Rd), and net phenylalanine balance (NB) were measured during a primed constant infusion of l-[ring-2H5]phenylalanine. Blood and muscle tissue samples were collected in the basal state and following ingestion of 40 g of AA given in 30 mL boluses every 10 min for 3 h. Serum and tissue cytokines and NF-κB expression in skeletal muscle were measured and compared to normative, healthy older controls (OC). Results: Skeletal muscle TNF-α, IL-6, and NF-κB were elevated in CA. FSR and model-derived protein synthesis (Rd) increased significantly from basal to AA (FSR: 0.052±0.009 vs. 0.120±0.008% h-1, P<0.001; Rd: 23.1±4.1 vs. 36.4±5.0 nmol min-1 100 mL leg-1, P≤0.05). Model-derived protein breakdown (Ra) remained unchanged from basal to AA. Phenylalanine NB improved from a negative basal value (-16±2) to zero (0.8±6 nmol min-1 100 ml leg-1, P≤0.05) following AA. Conclusion: Despite advanced cancer, ongoing therapy, and an enhanced inflammatory burden, AA were capable of acutely stimulating muscle protein synthesis in these patients.
KW - Cancer
KW - Inflammation
KW - Muscle protein synthesis
KW - Oral amino acids
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U2 - 10.1016/j.clnu.2007.07.004
DO - 10.1016/j.clnu.2007.07.004
M3 - Article
C2 - 17804123
AN - SCOPUS:36049008435
SN - 0261-5614
VL - 26
SP - 736
EP - 743
JO - Clinical Nutrition
JF - Clinical Nutrition
IS - 6
ER -