Zajicek G
Med Hypotheses. 1980 Dec;6(12):1315-25. doi: 10.1016/0306-9877(80)90118-8.
The theory presented regards cancer as a systemic disease initiated by carcinogens, and neoplasia as the organism's main defence against it. Carcinogens are assumed to destroy a vital substance "A" which is replenished by a second, "B", produced by neoplastic stem cells. Cancer progression is manifested by a gradual deterioration of the "A" producing machinery accompanied by a compensatory proliferation of neoplastic "B" producing stem cells whose size is therefore closely regulated so as to meet the organism's demands. Any stem cell pool reduction leading to a loss of "A" or "B" is followed by a proliferation of the remaining stem cells to replenish the loss. Such may be observed in chronic lymphoblastic leukemia maintaining a nearly constant elevated peripheral lymphoblast count. Following selective lymphoblast destruction the count is rapidly replenished to its pretreatment level. The same mechanism is assumed to explain the detrimental effect of some surgical interventions on cancer patients. Neoplastic progression is postulated to a obey a "stem cell conservation" principle which when violated is followed either by a stem cell replenishment or aggrevates the patient's conditions. This conservation law introduces a new definition of carcinogenesis: Any process reducing the "A" or "B" producing machinery is regarded as a carcinogen. A definition embracing, surgical extirpation of normal or neoplastic stem cells or cell destruction by irradiation, chemotherapy or chemical carcinogens.
所提出的理论认为癌症是一种由致癌物引发的全身性疾病，而肿瘤形成是机体对其的主要防御机制。假定致癌物会破坏一种重要物质“A”，而这种物质会由肿瘤干细胞产生的另一种物质“B”进行补充。癌症进展表现为产生“A”的机制逐渐恶化，同时伴随着产生肿瘤性“B”的干细胞的代偿性增殖，因此这些干细胞的大小受到严格调控以满足机体需求。任何导致“A”或“B”损失的干细胞池减少都会引发剩余干细胞的增殖以弥补损失。这在慢性淋巴细胞白血病中可见，其外周血淋巴细胞计数几乎持续维持在升高水平。在选择性破坏淋巴细胞后，计数会迅速恢复到治疗前水平。假定同样的机制可解释某些手术干预对癌症患者的有害影响。肿瘤进展被假定遵循“干细胞守恒”原则，一旦该原则被违反，要么会有干细胞补充，要么会使患者病情加重。这一守恒定律引入了致癌作用的新定义：任何减少产生“A”或“B”机制的过程都被视为致癌物。这一定义涵盖了对正常或肿瘤干细胞的手术切除，或通过辐射、化疗或化学致癌物进行的细胞破坏。
