Leibovici Judith, Itzhaki Orit, Kaptzan Tatiana, Skutelsky Ehud, Sinai Judith, Michowitz Moshe, Asfur Raida, Siegal Annette, Huszar Monica, Schiby Ginnette
Department of Pathology, Sackler Faculty of Medicine, Tel-Aviv University, 69978 Tel-Aviv, Israel.
Mech Ageing Dev. 2009 Jan-Feb;130(1-2):76-85. doi: 10.1016/j.mad.2008.03.004. Epub 2008 Mar 25.
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.
虽然已知肿瘤发病率会随年龄增长而增加,但矛盾的是,肿瘤生长和转移在老年时往往进展较慢。肿瘤的这种与年龄相关的生物学行为实际上对老年癌症患者施加了一种差异化的治疗方法。已经证明了几种与年龄相关的肿瘤进展减缓的机制:肿瘤细胞增殖减少、凋亡性细胞死亡增加、血管生成减少以及抗肿瘤免疫反应变化。我们推测,基于导致老年肿瘤进展速率降低的机制,有可能设计出年龄调整的治疗模式。基于这些机制,我们比较了不同治疗方法(诱导凋亡剂、氢化可的松和阿霉素、抗血管生成剂TNP - 470以及免疫调节剂左旋咪唑和卡介苗)对在年轻和老年小鼠中生长的两种实验性肿瘤(B16黑色素瘤和AKR淋巴瘤)的影响。据我们所知,大多数治疗方法在这两种肿瘤中对老年小鼠体内生长的肿瘤的抑制作用都比对年轻小鼠体内生长的肿瘤的抑制作用更强,这是抗肿瘤药物之前未描述过的一个特征。我们建议,在年轻患者的肿瘤中设计衰老条件可能也会减轻这些患者肿瘤的侵袭性。