Amino acid metabolism and inflammatory burden in ovarian cancer patients undergoing intense oncological therapy

Edgar Dillon, Elena Volpi, Robert R. Wolfe, Sandeep Sinha, Arthur P. Sanford, Concepcion D. Arrastia, Randall Urban, Shanon L. Casperson, Douglas Paddon-Jones, Melinda Sheffield-Moore

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)736-743
Number of pages8
JournalClinical Nutrition
Volume26
Issue number6
DOIs
StatePublished - Dec 2007

Fingerprint

Ovarian Neoplasms
Amino Acids
Phenylalanine
Muscle Proteins
Therapeutics
Leg
Skeletal Muscle
Muscles
Second Primary Neoplasms
Malnutrition
Interleukin-6
Neoplasms
Proteins
Eating
Cytokines
Drug Therapy
Serum

Keywords

  • Cancer
  • Inflammation
  • Muscle protein synthesis
  • Oral amino acids

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Endocrinology, Diabetes and Metabolism
  • Gastroenterology
  • Health Professions(all)
  • Medicine (miscellaneous)

Cite this

Amino acid metabolism and inflammatory burden in ovarian cancer patients undergoing intense oncological therapy. / Dillon, Edgar; Volpi, Elena; Wolfe, Robert R.; Sinha, Sandeep; Sanford, Arthur P.; Arrastia, Concepcion D.; Urban, Randall; Casperson, Shanon L.; Paddon-Jones, Douglas; Sheffield-Moore, Melinda.

In: Clinical Nutrition, Vol. 26, No. 6, 12.2007, p. 736-743.

Research output: Contribution to journalArticle

Dillon, Edgar ; Volpi, Elena ; Wolfe, Robert R. ; Sinha, Sandeep ; Sanford, Arthur P. ; Arrastia, Concepcion D. ; Urban, Randall ; Casperson, Shanon L. ; Paddon-Jones, Douglas ; Sheffield-Moore, Melinda. / Amino acid metabolism and inflammatory burden in ovarian cancer patients undergoing intense oncological therapy. In: Clinical Nutrition. 2007 ; Vol. 26, No. 6. pp. 736-743.
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abstract = "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.",
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AU - Dillon, Edgar

AU - Volpi, Elena

AU - Wolfe, Robert R.

AU - Sinha, Sandeep

AU - Sanford, Arthur P.

AU - Arrastia, Concepcion D.

AU - Urban, Randall

AU - Casperson, Shanon L.

AU - Paddon-Jones, Douglas

AU - Sheffield-Moore, Melinda

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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.

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