Designing ageing conditions in tumour microenvironment-a new possible modality for cancer treatment.
While tumour incidence is known to augment with age, paradoxically tumour growth and metastasis were often found to proceed at a slower rate at late ages. This age-related biological behaviour of tumours actually imposes a differential therapeutic approach to the old cancer patient. Several mechanisms of the age-related reduced tumour progression have been demonstrated: decreased tumour cell proliferation, increased apoptotic cell death, decreased angiogenesis and anti-tumoural immune response changes. We postulated that it might be possible to design age-adjusted treatment modalities based on the mechanisms responsible for the reduced tumour progression rate in the aged. Based on these mechanisms, we compared the effect of different treatments (apoptosis-inducing agents, Hydrocortisone and Adriamycin, anti-angiogenic agent, TNP-470, and immunomodulators-Levamisole and BCG) on two experimental tumours (B16 melanoma and AKR lymphoma) growing in young and old mice. Most treatments showed, in both tumours, a higher inhibitory effect on tumours growing in old mice than on those developing in young ones, to our knowledge, a feature not described before for anti-tumoural agents. We suggest that designing ageing conditions in tumours of young patients might possibly alleviate neoplastic aggressiveness in these patients as well.
Leibovici
Judith
J
Department of Pathology, Sackler Faculty of Medicine, Tel-Aviv University, 69978 Tel-Aviv, Israel. jlebov@post.tau.ac.il
Itzhaki
Orit
O
Kaptzan
Tatiana
T
Skutelsky
Ehud
E
Sinai
Judith
J
Michowitz
Moshe
M
Asfur
Raida
R
Siegal
Annette
A
Huszar
Monica
M
Schiby
Ginnette
G
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D018450:Disease Progression; D008223:Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D012720:Severity of Illness Index; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015996:Survival Rate
D000970:Antineoplastic Agents