The clinical applications of cell kinetics in cancer therapy.
The clinical applications of cell kinetics in cancer therapy.
复制标题
细胞动力学在癌症治疗中的临床应用。
DOI：
10.1146/annurev.pa.17.040177.002525
复制
发表时间：
1977
影响因子：
12.5
通讯作者：
J. Hart
中科院分区：
文献类型：
--
作者：
R. Livingston;J. Hart
出于多种原因，参与癌症患者护理的临床医生对细胞动力学研究很感兴趣。激发这种兴趣的最初假设是，使用 FLM（标记有丝分裂分数）曲线等工具，可以证明癌细胞和正常细胞在细胞周期各阶段的持续时间方面存在主要差异。除了癌细胞一般在 G2 期表现出一定程度的延长外，尚未发现实际情况如此 (l)。第二个早期假设是，一般来说，癌细胞群的增殖分数比正常细胞群高得多：这是设计 S 期活性抗代谢物的主要理由。事实上，通过氚化胸苷 (3HTdR) 标记测量，人类白血病原始细胞的增殖水平通常低于相应的正常骨髓前体细胞 (2)。与骨髓或胃肠粘膜等正常宿主组织相比，大多数人类实体瘤的生长分数相对较低。第三个假设虽然尚未解决，但仍然可行，即通过用某种药物进行适当的预处理，肿瘤细胞可以有效地、差异性地同步或募集，以便更多的肿瘤细胞处于细胞周期的某个阶段（例如 S），在该阶段它们可以被随后施用的“执行者”药物杀死。目前已得到多项研究支持的一个相关假设是，治疗前增殖状态与临床反应之间存在直接相关性：肿瘤生长分数较高的患者比肿瘤生长分数较低的患者更有可能做出反应。
The study of cell kinetics has been of interest to clinicians involved in the care of cancer patients for several reasons. An initial hypothesis which motivated this interest was that, using tools like the FLM (fraction of labeled mitoses) curve, major differences would be demonstrated between cancer cells and normal cells in terms of duration of the phases of cell cycle. Except that cancer cells in general show some prolongation in G2, this has not been found to be the case (l). A second early hypothesis was that, in general, cancer cell populations would have a much higher proliferating fraction than normal cell populations: a major rationale for the design of S-phase active antimetabolites. In fact, human leukemic blasts usually have a lower level of proliferation, as measured by tritiated thymidine (3HTdR) labeling, than corresponding normal bone marrow precursors (2). Most human solid tumors have a relatively low growth fraction, compared to normal host tissues like the bone marrow or gastrointestinal mucosa. A third hypothesis, which remains viable though unresolved, is that tumor cells can be efficiently and differentially synchronized or recruited, by appropriate pre treatment with some agent, so that more of them are in a phase of the cell cycle (such as S) where they can be killed by a subsequently administered "executor" agent. A related hypothesis, now supported by several studies, is that a direct correlation exists between pretreatment proliferative state and clinical response: that patients with higher growth fraction tumors are more likely to respond than those with lower