Extremity metabolism in the cachectic, VX-2 carcinoma-bearing rabbit.
The pathophysiology of skeletal muscle loss in cancer cachexia is poorly understood. Immature, male, New Zealand White rabbits (TBs; n = 11) were implanted with VX-2 carcinoma and various indices of systemic and limb metabolism were examined in comparison with pair-fed controls (PFCs; n = 9) and normal controls (NCs; n = 22) fed ad lib. The TBs became hypophagic and experienced reduced growth relative to both control groups (P << 0.001). At 7 weeks (tumor burden 3-6% of body weight; no metastasis) the TBs had the following statistically significant differences from NCs: anemia, neutrophilic granulocytosis and thrombocytosis, hypercalcemia, hypoinsulinemia, elevated plasma triglycerides and altered plasma amino acids, increased hind limb effluxes of lactate and most amino acids. These alterations were not caused by hypophagia, since the PFCs were normal at 7 weeks with regard to all measured parameters except body weight and limb flow, both of which were reduced. The decrease in flow (P < 0.05) apparently contributed to conservation of skeletal muscle amino acids in the PFCs. Young New Zealand White rabbits implanted with VX-2 carcinoma manifest tumor burden, wasting, and metabolic alterations qualitatively similar to those seen with many human cancers.
Conlon
K C
KC
Surgical Metabolism Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Bading
J R
JR
McDermott
E W
EW
Corbally
M T
MT
Tolvo
A J
AJ
Brennan
M F
MF
D000596:Amino Acids / Q000097:blood / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002100:Cachexia / Q000209:etiology / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D004435:Eating; D005121:Extremities / Q000098:blood supply; D005934:Glucagon / Q000097:blood; D006410:Hematopoiesis; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D009132:Muscles / Q000098:blood supply / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D015431:Weight Loss
D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D005934:Glucagon; D002118:Calcium