Liver export protein synthetic rates are increased by oral meal feeding in weight-losing cancer patients

Abstract

We have demonstrated previously that, in the fasting state, whereas albumin synthesis is similar in cachectic cancer patients compared with controls, fibrinogen synthesis is increased. Whether synthesis of these proteins is altered after an oral meal was examined in eight weight-losing pancreatic cancer patients and six healthy controls by use of an intravenous flooding dose of [(2)H(5)]- or [(2)H(8)]phenylalanine. Cancer patients had a median weight loss of 19%, a significantly lower serum albumin concentration, and a significantly higher plasma fibrinogen concentration than controls (P < 0.005). Fasting albumin synthesis rates were similar between cancer patients and controls (median total synthesis rate 11.3 vs. 13.9 g/day, respectively) and rose on feeding by a similar degree (median 29 and 24%). The fasting fibrinogen total synthetic rate was significantly higher in cancer patients than in controls (median 3.3 vs. 1.0 g/day, P = 0.0019). In cancer patients in the fed state, fibrinogen synthetic rate rose by a median of 38% (P = 0.012), whereas in controls there was no significant change. These findings demonstrate significant upregulation by feeding of acute-phase protein synthesis in cachectic cancer patients.

Pretreatment serum albumin: a prognostic indicator of survival in oral cancer

“…36 As part of the systemic inflammatory response to the tumor, proinflammatory cytokines and growth factors are released and have a profound catabolic effect on host metabolism. 37 Interleukin-6, produced by the tumor or surrounding cells, stimulates liver production of acute-phase reaction proteins (such as CRP and fibrinogen) in both the fasted and fed states. 37 This increases the demand for certain amino acids, which if limited in the diet, may be obtained from breakdown of skeletal muscle.…”

“…A vast majority (>70%) of more than one billion population of India lives in rural areas, which have inadequate access to trained providers and limited health services. As a result, most of the cases are diagnosed at later stages which result in low treatment outcomes and poor 5-year survival rate of approximately 37% (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). 2 Various clinical, biochemical, and histological prognostic factors have been identified in the literature, some generic to all cancers and some specific for oral cavity cancer.…”

Reprioritisation of Liver Export Protein Synthesis in Patients with Decompensated Alcoholic Liver Disease

“…Studies in patients with cancer and chronic heart failure show that fibrinogen synthesis is preserved or increased as part of the acute phase response [15,22,23]. To date, there are limited data on albumin and fibrinogen synthesis rates in patients with decompensated alcohol related liver cirrhosis.…”

“…Blood samples were drawn at 10, 20, 40, 60, 80, 120 min after the start of the infusion into EDTA tubes from the contralateral arm, spun down in a cooled centrifuge at 4°C for 15 min, and stored at -80°C. As tracer will reside in the protein pool for weeks [15], each subject received one of the two phenylalanine isotopomers at baseline with the other at follow-up.…”

“…Of the export component, albumin synthesis (approximately 80%) and fibrinogen synthesis (approximately 10%) are quantitatively the most important [14,15]. These proteins play a key role in the systemic inflammatory response, with albumin recognised as a negative acute phase reactant and fibrinogen a positive acute phase reactant [16,17].…”