Effect of local hyperthermia on blood flow and microenvironment: a review.
Effect of local hyperthermia on blood flow and microenvironment: a review.
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作者：
C. Song
肿瘤中的血流在不同的肿瘤类型之间变化很大。即使在同一肿瘤中，血管和血流的分布也是相当不均匀的。随着肿瘤变大，肿瘤血流量通常会减少，部分原因是血管床的逐渐恶化以及肿瘤细胞群相对于血管床的快速生长。与肿瘤中的血流量比正常组织中的血流量少的一般概念相反，在正常温度条件下，许多肿瘤，特别是小肿瘤中的血流量实际上大于周围正常组织中的血流量。然而，与正常组织血流相比，肿瘤血流在加热时增加的能力似乎相当有限。因此，在肿瘤中通过血流的热耗散比在正常组织中慢，并且因此在加热期间肿瘤的温度升高得高于正常组织中的温度。然而，肿瘤的优先加热可能并不总是实现的，因为尽管在加热期间正常组织血流显著增加，但一些肿瘤中的相对血液灌注仍然大于周围正常组织中的相对血液灌注。肿瘤中的脉管系统可在可改变但不损害正常组织的脉管系统的温度下被显著损害。在加热时，肿瘤内环境变得酸性、缺氧和营养缺乏，这可能是由于血管损伤。这种加热肿瘤中的次优环境增强了肿瘤细胞对高温的反应，抑制了热损伤的修复，并且还干扰了热耐受性的发展。酸性环境似乎也会增强肿瘤细胞在高温下对某些药物的反应。由血流变化引起的肿瘤和正常组织的氧合变化可能对联合使用这两种方式的不同序列的热疗和放疗的有效性具有重要意义。由于血流变化而引起的药物在肿瘤和正常组织中分布的变化也将决定热疗结合化疗的最佳使用。
The blood flow in tumors varies considerably among different tumor types. Even in the same tumor, the distribution of vasculature and blood flow is quite heterogeneous. The tumor blood flow generally decreases as the tumors grow larger, owing partially to progressive deterioration of vascular beds and to the rapid growth of tumor cell population relative to vascular beds. Contrary to the general notion that blood flow is less in tumors than in normal tissues, blood flow in many tumors, particularly in small tumors, is actually greater than that in surrounding normal tissues at normothermic conditions. Compared to the normal tissue blood flow, however, the capacity of tumor blood flow to increase upon heating appears to be rather limited. Consequently, the heat dissipation by blood flow in tumors is slower than that in normal tissues, and thus the temperature of tumor rises higher than that in normal tissue during heating. Preferential heating of tumors, however, may not be achieved all the time because the relative blood perfusion in some tumors remains greater than that in the surrounding normal tissues despite the profound increase in normal tissue blood flow during heating. The vasculature in tumor can be significantly damaged at temperatures which may alter but do not damage the vasculature of normal tissue. Upon heating, the intratumor environment becomes acidic, hypoxic, and nutritionally deprived due probably to vascular damage. Such a suboptimal environment in the heated tumors potentiates the response of tumor cells to hyperthermia, inhibits the repair of thermal damage, and also interferes with the development of thermal tolerance. The acidic environment also appears to potentiate the response of tumor cells to certain drugs at elevated temperatures. The changes in oxygenation of tumors and normal tissues caused by the changes in blood flow may have significant implications in the effectiveness of different sequences of hyperthermia and radiotherapy in the combined use of these two modalities. Changes in the distribution of drugs in tumors and normal tissues due to changes in blood flow will also determine the optimal use of hyperthermia in conjunction with chemotherapy.