Zajicek G
Med Hypotheses. 1985 Mar;16(3):303-13. doi: 10.1016/0306-9877(85)90013-1.
The theory presented herewith provides a unified explanation for neoplasia and teratogenesis, both regarded here as stem cell disorders. Proliferating cells in the organism form two mutually exclusive classes, immortal stem cells and transitional cells whose life span is limited. Any lasting change in the organism e.g. tissue differentiation or neoplasia, is determined by stem cells. Congenital as well as adult neoplasms exhibit three key features: maturation arrest, stem cell pool expansion and increased cell turnover and they progress through the following states: dysplasia, neoplasia in situ, benign stage (e.g. polyp) and overt neoplasia. The neoplasm is regarded here as an organ with a purpose intended to supply the organism with a missing substance. Besides serving as tissue progenitors, stem cells are postulated here to secrete a substance 'A' necessary for a proper tissue function. Carcinogens interfere with the substance production mainly by depleting stem cells so that less 'A' is produced. The capacity of the adult to replenish the depleted stem cells is limited, and the missing substance has to be formed by an alternative way i.e. by Neoplasia. The 'A' substitute formed by the neoplasm denominated as 'B' is however less efficient than 'A'. Neoplastic growth thus depends upon the relative abundance of substances 'A' and 'B'. Since in the growing organism, stem cells multiply, some of the missing 'A' is replenished by them and the neoplasm may regress.
本文提出的理论为肿瘤形成和致畸发生提供了统一的解释，在此二者均被视为干细胞紊乱。生物体中的增殖细胞形成两个相互排斥的类别，即永生干细胞和寿命有限的过渡细胞。生物体中的任何持续变化，例如组织分化或肿瘤形成，均由干细胞决定。先天性肿瘤和成人肿瘤均表现出三个关键特征：成熟停滞、干细胞池扩张和细胞更新增加，并且它们会经历以下状态：发育异常、原位肿瘤、良性阶段（例如息肉）和明显的肿瘤。此处将肿瘤视为一个旨在为生物体提供缺失物质的有特定目的的器官。除了作为组织祖细胞外，本文推测干细胞会分泌一种对正常组织功能必需的物质“A”。致癌物主要通过消耗干细胞来干扰物质的产生，从而使“A”的产生减少。成年人补充耗尽的干细胞的能力是有限的，缺失的物质必须通过另一种方式即肿瘤形成来形成。然而，由肿瘤形成的“A”替代物“B”的效率低于“A”。因此，肿瘤生长取决于物质“A”和“B”的相对丰度。由于在生长的生物体中干细胞会增殖，一些缺失的“A”会由它们补充，肿瘤可能会消退。
