Effect of a fluorinated pyrimidine on cachexia and tumour growth in murine cachexia models: relationship with a proteolysis inducing factor.
The fluorinated pyrimidine nucleoside, 5'-deoxy-5-fluorouridine (5'-dFUrd) has been shown to effectively attenuate the progress of cachexia in the murine adenocarcinomas MAC16 and colon 26 as well as in the human uterine cervical carcinoma xenograft, Yumoto. Although concomitant inhibition of tumour growth was observed in all three models this was not sufficient to account for the preservation of body weight. An attempt has been made to correlate the anti-cachectic activity of 5'-dFUrd with the presence of a tumour produced proteolysis-inducing factor (PIF), thought to be responsible for the development of cachexia in the MAC16 model. Two variants of colon 26 adenocarcinoma were employed, clone 20 which produces profound cachexia, and clone 5 which produces no change in body weight in recipient animals. Mice bearing the colon 26, clone 20 variant showed evidence for the presence of PIF in tumour, serum and urine, while there was no evidence for the presence of PIF in tumour or body fluids of mice bearing the clone 5 tumours. Treatment of animals bearing the clone 20 variant with 5'-dF Urd led to the disappearance of PIF from the tumour, serum and urine concomitant with the attenuation of the development of cachexia. The human cervical carcinoma, Yumoto, which also induced cachexia in recipiant animals, showed expression of PIF in tumour, serum and urine in control and vehicle-treated mice, but was absent in mice treated with 5'-dFUrd. Thus in these experimental models cachexia appears to be correlated with the presence of PIF.
Hussey
H J
HJ
Pharmaceutical Sciences Research Institute, Aston University, Birmingham, UK.
Todorov
P T
PT
Field
W N
WN
Inagaki
N
N
Tanaka
Y
Y
Ishitsuka
H
H
Tisdale
M J
MJ
D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D019167:Appetite Stimulants / Q000494:pharmacology / Q000627:therapeutic use*; D001798:Blood Proteins / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D002999:Clone Cells / Q000473:pathology / Q000637:transplantation; D003110:Colonic Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005467:Floxuridine / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009124:Muscle Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D011509:Proteoglycans; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000473:pathology / Q000637:transplantation; D002583:Uterine Cervical Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D019167:Appetite Stimulants; D001798:Blood Proteins; D015850:Interleukin-6; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D011509:Proteoglycans; C042057:proteolysis-inducing peptide; D005467:Floxuridine; C025034:doxifluridine