Mueller-Klieser W, Walenta S, Kelleher D K, Dinh H, Marx E, Vaupel P
Institute of Physiology and Pathophysiology, University of Mainz, Germany.
Int J Hyperthermia. 1996 Jul-Aug;12(4):501-11. doi: 10.3109/02656739609023527.
The present study was undertaken to exploit pathophysiological properties of solid tumours for a tumour-specific therapy. Experiments were carried out on DS-sarcomas implanted s.c. in the hind foot dorsum of Sprague Dawley rats. Treatment strategies included tumour acidification, lactate accumulation and disturbance of the microcirculation by induced systemic hyperglycaemia/hyperlact-acidaemia (15-25/10 mmol/L; for 60 min) as well as localized hyperthermia (water-bath; 43 degrees C, 30 min.). A special infusion solution was developed for the systemic treatment containing glucose, lactic acid and organic buffer without inorganic ions. Growth kinetics of tumour volume and animal survival were taken as endpoints in order to quantify therapeutic efficiency. After a single treatment with combined modalities, i.e., with hyperglycaemia/hyperlactacidaemia and hyperthermia, approximately 50% of the tumours showed complete remission in three independent series of experiments; around 40% of the animals survived more than two months. In the untreated control group, all animals died from the disease within 10-15 days after tumour implantation. The overall effect on tumour volume changes of the combined therapy was supra-additive compared to that of treatment with hyperthermia or hyperglycaemia/hyperlactacidaemia alone. However, treated animals either showed a dramatic response to the combination of treatments with complete tumour remission or hardly responded at all, justifying a subdivision into responders and non-responders. Pathophysiological mechanisms responsible for this behaviour have to be elucidated in future studies. Nevertheless, the present study represents an approach to an efficient tumour therapy with a potential application in clinical oncology in the not too distant future.
本研究旨在利用实体瘤的病理生理特性进行肿瘤特异性治疗。实验在Sprague Dawley大鼠后足背皮下植入的DS-肉瘤上进行。治疗策略包括肿瘤酸化、乳酸积累以及通过诱导全身性高血糖/高乳酸血症（15 - 25/10 mmol/L；持续60分钟）和局部热疗（水浴；43摄氏度，30分钟）来干扰微循环。开发了一种特殊的输注溶液用于全身治疗，该溶液含有葡萄糖、乳酸和有机缓冲剂，不含无机离子。以肿瘤体积的生长动力学和动物存活率作为终点指标，以量化治疗效果。在采用联合治疗方式（即高血糖/高乳酸血症和热疗）进行单次治疗后，在三个独立的实验系列中，约50%的肿瘤显示完全缓解；约40%的动物存活超过两个月。在未治疗的对照组中，所有动物在肿瘤植入后10 - 15天内死于该疾病。与单独使用热疗或高血糖/高乳酸血症治疗相比，联合治疗对肿瘤体积变化的总体效果具有超相加性。然而，接受治疗的动物要么对联合治疗有显著反应，肿瘤完全缓解，要么几乎没有反应，这表明可将其分为反应者和无反应者。这种行为背后的病理生理机制有待未来研究阐明。尽管如此，本研究代表了一种高效肿瘤治疗方法，在不久的将来有可能应用于临床肿瘤学。
