Age-adjusted antitumoral therapy based on the demonstration of increased apoptosis as a mechanism underlying the reduced malignancy of tumors in the aged.
In view of the constant increase in the aged population, age-adjusted cancer therapy becomes an urgent target. Although cancer incidence rises with age, paradoxically, growth rate and metastasis often proceed at a slower rate in the aged. Determining the mechanism(s) underlying this reduced tumor progression in the old might have implications for a rational design of age-adjusted therapy. Thus far, decreased cell proliferation or immune response modifications were suggested as possible mechanisms. We show here that an increased tendency to apoptotic tumor cell death in the aged could constitute an additional mechanism. Based on this mechanism, we compared the therapeutic efficacy of two apoptosis inducers, hydrocortisone and adriamycin, on AKR lymphoma and B16 melanoma growth in young and old mice. Treatment with hydrocortisone acetate inhibited tumor growth practically only in old mice in the two tumor systems. Similar effects were obtained with adriamycin treatment of AKR lymphoma but opposite results were seen with B16 melanoma. We thus demonstrated, in three of the four tumor-therapeutic modality systems examined, an age-related antitumoral efficacy of two apoptosis-inducing agents, with tendency for a remarkably more pronounced effect in aged mice.
Itzhaki
Orit
O
Department of Pathology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 69978, Israel.
Kaptzan
Tatiana
T
Skutelsky
Ehud
E
Sinai
Judith
J
Michowitz
Moshe
M
Siegal
Annette
A
Schibi
Ginnette
G
Huszar
Monica
M
Ben-Dor
Lya
L
Leibovici
Judith
J
D000367:Age Factors; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005434:Flow Cytometry; D006854:Hydrocortisone / Q000008:administration & dosage / Q000627:therapeutic use; D008223:Lymphoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D051379:Mice; D016019:Survival Analysis; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D000903:Antibiotics, Antineoplastic; C092567:adriamycin-14-valerate; D004317:Doxorubicin; D006854:Hydrocortisone