Biological rationale for hyperthermia in cancer treatment (II).
Biological rationale for hyperthermia in cancer treatment (II).
复制标题
癌症治疗中热疗的生物学原理（II）。
DOI：
--
复制
发表时间：
1994
期刊：
影响因子：
--
通讯作者：
K. Engin
中科院分区：
文献类型：
--
作者：
K. Engin
热疗（HT）在过去的二十年中获得了极大的兴趣。高温致细胞死亡的性质与辐射致细胞死亡有很大不同。细胞周期的g1期对HT的抗性最强，而s期细胞对HT非常敏感。除了热诱导的细胞毒性外，高温还使细胞对低LET电离辐射敏感。热细胞毒性的作用机制不同于电离辐射。与对电离辐射的反应不同，热细胞毒性受耐热性、低pH值和营养剥夺的影响，但与急性缺氧无关。此外，相对于正常组织，血流影响肿瘤的加热特性，加热后可能发生血管塌陷。耐热性是由于暴露于高温和其他细胞毒性物质而引起的对高温的非遗传抗性。在低于43摄氏度的温度下，温度耐受性在2-3小时内产生。细胞在短时间内暴露于高于43摄氏度的温度下，对低于43摄氏度的温度敏感。这被称为“降温加热，SDH”。SDH是由于暴露在高温下对耐热性发育的抑制造成的。细胞通过急剧降低pH值而对高温损伤敏感，并且在低pH值下，耐热性发育降低。降低的pH值也增强了热辐射敏化。由于大部分肿瘤细胞的pH值都很低，而且这些肿瘤细胞很可能是缺氧的，并且具有放射抗性，这就为将高温疗法与放射疗法结合起来治疗人类肿瘤提供了最有力的理由之一。肿瘤中的新生血管不像正常组织中的血管那样对升高的温度做出反应，这些血流的差异可能导致肿瘤选择性加热。高温能显著增强缺氧细胞中电子亲和放射增敏剂的细胞毒性。HT使细胞对许多细胞毒性药物敏感，甚至将一些无害的药物转化为剧毒药物。高温下化学致敏可通过增加反应速率、增加渗透性或减少修复性发生。由于烷基化剂和顺铂在所有高温下都能增强，因此最有希望的高温化学增敏作用似乎是与烷基化剂和顺铂一起进行的。
Hyperthermia (HT) has gained a great interest in the past two decades. The nature of hyperthermia-induced cell lethality is quite different from that of radiation-induced killing. The G1-phase of the cell cycle is the most resistant to HT while S-phase cells are quite sensitive. In addition to heat-induced cytotoxicity, HT sensitizes cells to low LET ionizing radiation. The mechanism of heat cytotoxicity is distinct from that of ionizing radiation. Unlike the response to ionizing radiation, heat cytotoxicity is influenced by thermotolerance, low pH and nutritional deprivation, but is independent of acute hypoxia. Also, blood flow influences the heating characteristics of a tumor relative to normal tissue, and vascular collapse may occur after heating. Thermotolerance is a nonheritable resistance to HT induced by exposure to heat and other cytotoxic agents. Thermotolerance develops within 2-3 h during exposure to temperatures less than 43 degrees C. Cells exposed for a brief period to temperatures higher than 43 degrees C are sensitized to exposure to temperatures below 43 degrees C. This is called "stepdown heating, SDH". SDH results from the inhibition of thermotolerance development by exposure to the high temperature. Cells are sensitized to HT damage by acutely lowering pH, and thermotolerance development is reduced at low pH. Reduced pH also enhances thermoradiosensitization. Since much of a tumor population is at low pH, and these tumor cells are very likely to be hypoxic and radioresistant, this offers one of the strongest reasons for combining HT with radiation therapy in the treatment of human tumors. The neovasculature in tumors does not respond to increased temperatures as do blood vessels in normal tissues, and these differences in blood flow may lead to selective tumor heating. HT dramatically enhances the cytotoxicity of the electron affinic radiosensitizers in hypoxic cells. HT sensitizes the cell to many cytotoxic agents and even converts some drugs that are innocuous to highly toxic. HT chemosensitization may occur by an increased reaction rate, increased permeability, or decreased repair. The most promising chemosensitization by HT would seem to be with alkylating agents and cis-platinum since they are enhanced at all elevated temperatures.