De Lerma Barbaro Andrea
Biomedical Research Division, Department of Theoretical and Applied Sciences, University of Insubria, Busto Arsizio, Varese, Italy.
Oncol Rep. 2015 Oct;34(4):1635-49. doi: 10.3892/or.2015.4164. Epub 2015 Jul 31.
Cachexia is a wasting syndrome that afflicts end-stage cancer patients. Whereas a consensus statement for a definition of cachexia recently has been accomplished, a useful measurement for this condition at present is lacking. The aim of the present review is to discuss the advantage of introducing the measurement of tumor burden for a better overall evaluation of cachexia. Our suggestion ensues from a somewhat novel perspective in the field of infectious disease research where a careful measurement of the pathogen load, between i.e. different host genotypes, leads to the definition of the concept of tolerance to the infectious insult. Indeed tolerance concurs, together the more classical resistance, in maintaining the host reproductive fitness or health state. Noticeably a similar reasoning may apply to tumor biology as well. Whereas the extent of cachexia increases with tumor burden, the relationship between these two correlates of tumor progression fluctuates in a broad range. We have selected from the literature studies in the rodent model where significant variation in the course of the wasting illness during cancer was observed and quantitatively assessed comparing experimental groups marked by different genotype, drug treatment, diet or gender. These studies may be further classified in two categories: the former where the experimental condition associated to milder cachexia is accompanied to a lesser tumor burden, the latter where the inhibition of cachexia results disentangled from the tumor burden, that is the whole number of cancer cells results unchanged or even, paradoxically, is increased. In addition we survey, even in the context of human malignancy, the significance and feasibility of plotting quantitative estimates of cachexia against the whole tumor burden. Ultimately, the principal endeavor of introducing the measurement of tumor burden, in both experimental and clinical oncology, may be to achieve a better assessment of the inter-individual variation in the host vulnerability to cancer cachexia.
恶病质是一种折磨晚期癌症患者的消耗综合征。尽管最近已达成关于恶病质定义的共识声明,但目前仍缺乏针对这种病症的有效测量方法。本综述的目的是讨论引入肿瘤负荷测量对于更全面评估恶病质的优势。我们的建议源自传染病研究领域中一个较为新颖的观点,即在传染病研究领域,仔细测量病原体负荷(例如在不同宿主基因型之间)会引出对感染性损伤耐受性概念的定义。事实上,耐受性与更为经典的抗性共同作用,以维持宿主的生殖适应性或健康状态。值得注意的是,类似的推理也可能适用于肿瘤生物学。虽然恶病质的程度随肿瘤负荷增加,但肿瘤进展的这两个相关因素之间的关系在很大范围内波动。我们从啮齿动物模型的文献研究中进行了筛选,在这些研究中观察到癌症期间消瘦疾病进程存在显著差异,并对以不同基因型、药物治疗、饮食或性别标记的实验组进行了定量评估。这些研究可进一步分为两类:一类是与较轻恶病质相关的实验条件伴随着较小的肿瘤负荷;另一类是恶病质的抑制结果与肿瘤负荷无关,即癌细胞总数不变甚至反常地增加。此外,即使在人类恶性肿瘤的背景下,我们也调查了绘制恶病质定量估计值与整个肿瘤负荷关系图的意义和可行性。最终,在实验肿瘤学和临床肿瘤学中引入肿瘤负荷测量的主要努力可能是为了更好地评估宿主对癌症恶病质易感性的个体间差异。