Effects of all-trans retinoic acid on tumor recurrence and metastasis.
OBJECTIVE
All-trans-retinoic acid (ATRA) promotes cell differentiation. We have studied its effect on the local recurrence and metastatic spreading of an experimental rhabdomyosarcoma in rats.


METHODS
syngenic rhabdomyosarcoma cells (S4MH) were inoculated s.c. in male WAG/RijCrl rats. After 25 days tumors were excised and a 40% hepatectomy was performed for all animals. Ten days later the rats were sacrificed and a thorough necropsy was performed. The animals were randomly allocated to receive daily doses of ATRA (5 mg/kg, i.p.) or its solvent (Clinoleic/ethanol 90/10), starting three days before surgery until the end of the experiment.


RESULTS
ATRA reduced the incidence of local recurrence from 70 to 33% (p < 0.05), but the tumor size was not altered (1.8 vs. 2.0 cc). Regarding inguinal metastasis, there was a six-fold decrease (0.2 vs. 1.2 cc; p < 0.05) in mean tumor volume, although the rate of this proliferation increased sharply (86 vs. 29%; p < 0.05) for treated animals. The volume of the retroperitoneal tumor masses also decreased with ATRA (0.7 vs. 5.1 cc; p < 0.05), but the difference in rate was not significant (71 vs. 67%). Lung metastases, which were present in 100% of control animals, were found in only 33% of treated rats, while the mean number of metastatic foci dropped from 26.7 to 5.7 (p < 0.05).


CONCLUSIONS
Protocols including retinoid administration prior to and following primary tumor excision could help in controlling both recurrence and metastatic progression in surgically treated rhabdomyosarcoma.
Laboratory of Experimental Surgery, Faculty of Medicine and Dentistry, Lejona, Vizcaya, Spain.
I
I
García-Alonso
T
T
Palomares
A
A
Alonso-Varona
B
B
Castro
M
M
Del Olmo
V
V
Portugal
J
J
Méndez
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D019042:Muscle Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D014212:Tretinoin / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D014212:Tretinoin