Recombinant human erythropoietin attenuates weight loss in a murine cancer cachexia model.
BACKGROUND
Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact of recombinant human erythropoietin (RhEPO) and increased inspiratory oxygen concentrations on weight loss in tumor-bearing mice.


METHODS
Fragments of the murine C26-B adenocarcinoma were implanted in 60 BALB/c-mice. The mice were divided into four groups and assigned to: (A) no treatment; (B) RhEPO- administration (25 IU daily from day 1-11, three times per week from day 12); (C) RhEPO and 25% oxygen; and (D) RhEPO and 35% oxygen. Three control groups of four healthy mice each received the same treatment as groups A, B, and D, respectively. Hematocrit and hemoglobin levels, tumor volume, and body weight were monitored. At day 17 the experiment was terminated and the serum lactate concentration was measured. The tumors were excised and weighed and, for each mouse, the percentage weight loss was calculated. The impact of tumor weight and the treatments on lactate concentration and weight loss was evaluated.


RESULTS
Significant positive correlations were found between tumor weight and lactate concentration and between tumor weight and percentage weight loss. In the mice with the largest tumors, RhEPO displayed a significant weight loss-reducing effect, and a significant negative correlation was found between hemoglobin concentration and weight loss. An oxygen-rich environment did not appear to influence weight loss.


CONCLUSIONS
Anaerobic glycolysis in a growing C26-B tumor is related to weight loss. RhEPO administration results in a reduction of the percentage weight loss; this effect is probably mediated by an increased hemoglobin concentration.
van Halteren
H K
HK
Department of Internal Medicine, Oosterschelde Hospital, PO Box 106, 4460 BB, Goes, The Netherlands. Hvanhalteren@soz.nl
Bongaerts
G P A
GP
Verhagen
C A M
CA
Kamm
Y J L
YJ
Willems
J L
JL
Grutters
G J
GJ
Koopman
J P
JP
Wagener
D J Th
DJ
D000230:Adenocarcinoma / Q000150:complications* / Q000378:metabolism; D000818:Animals; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D006019:Glycolysis; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D001239:Inhalation; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000008:administration & dosage*; D011994:Recombinant Proteins; D015431:Weight Loss / Q000187:drug effects*
D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D010100:Oxygen