Thistlethwaite A J, Alexander G A, Moylan D J, Leeper D B
Int J Radiat Oncol Biol Phys. 1987 Apr;13(4):603-10. doi: 10.1016/0360-3016(87)90078-2.
Nine patients with metastatic or recurrent superficial tumors of varying size and histology were administered 100 g oral glucose to investigate whether hyperglycemia can selectively lower tumor pH. pH was measured by a 21 ga modified glass needle electrode inserted through an 18 ga open-ended Angiocath. Serum glucose was monitored every 7.5 min by finger stick and a blood glucose analyzer. Tumor pH was measured over 50-80 min concomitantly with determination of blood glucose. In five nondiabetic patients (eight measurement points) tumor pH decreased 0.05-0.5 units from a pre-glucose range of 6.8-7.4 (7.14 +/- 0.08) to 6.4-7.3 (6.90 +/- 0.10) as blood glucose increased from a baseline of 80-120 mg/dl to 165-215 mg/dl. There was considerable heterogeneity from patient to patient regardless whether blood glucose increased to a peak at 40-60 min post-ingestion and then decreased, or whether it remained elevated up to the end of the 80 min observation period. In general, tumor pH decreased as blood glucose increased and then continued to fall throughout the period of observation. In one patient, tumor pH did not change although blood glucose increased to 175 mg/dl. Normal tissue pH was 7.36 +/- 0.02 when determined on four occasions in three patients (subcutaneous and intramuscular sites), and was unaffected by glucose administration. As a further control for tumor tissue and pH probe stability, pH probes in two patients were left in place for 30 min before glucose ingestion. The tumor pH was stable for the entire interval. Interestingly, three patients had an abnormal glucose response: two of those patients (one patient on two separate occasions) had an increase in blood glucose to 230-260 mg/dl in 40-60 min and pH actually increased 0.1-0.3 units. The third patient had a transient increase in blood glucose to 290 mg/dl along with a corresponding increase and subsequent decrease in tumor pH. In summary, whether glucose was given pre- or post-hyperthermia, independently of position in the tumor, and independently of whether pH increased or decreased, the slope of the curve of pH = f(time) was similar in a given patient tumor on all measurement occasions. These preliminary results suggest that hyperglycemia may be useful in non-diabetic patients, and perhaps in diabetic patients given insulin, to selectively reduce tumor pH and sensitize tumors to hyperthermia.
对9例患有不同大小和组织学类型的转移性或复发性浅表肿瘤的患者给予100 g口服葡萄糖，以研究高血糖是否能选择性降低肿瘤pH值。通过一根21号改良玻璃针电极，经一根18号开口式血管穿刺针插入来测量pH值。每隔7.5分钟通过手指采血并用血糖仪监测血清葡萄糖水平。在测定血糖的同时，在50 - 80分钟内测量肿瘤pH值。在5例非糖尿病患者（8个测量点）中，随着血糖从基线80 - 120 mg/dl升高至165 - 215 mg/dl，肿瘤pH值从葡萄糖摄入前的6.8 - 7.4（7.14±0.08）下降0.05 - 0.5个单位至6.4 - 7.3（6.90±0.10）。无论血糖在摄入后40 - 60分钟达到峰值然后下降，还是在80分钟观察期结束时一直保持升高，患者之间都存在相当大的异质性。一般来说，肿瘤pH值随着血糖升高而降低，并且在整个观察期内持续下降。有1例患者，尽管血糖升高至175 mg/dl，但肿瘤pH值未发生变化。在3例患者的4个部位（皮下和肌肉部位）进行了4次测量，正常组织pH值为7.36±0.02，且不受葡萄糖给药的影响。作为对肿瘤组织和pH探头稳定性的进一步对照，在2例患者中，在摄入葡萄糖前将pH探头留置原位30分钟。在整个时间段内肿瘤pH值保持稳定。有趣的是，3例患者有异常的葡萄糖反应：其中2例患者（1例患者在两个不同时间）在40 - 60分钟内血糖升高至230 - 260 mg/dl，而pH值实际上升高了0.1 - 0.3个单位。第3例患者血糖短暂升高至290 mg/dl，同时肿瘤pH值相应升高并随后下降。总之，无论葡萄糖是在热疗前还是热疗后给予，与肿瘤位置无关，也与pH值升高或降低无关，在给定患者肿瘤的所有测量情况下，pH = f（时间）曲线的斜率相似。这些初步结果表明，高血糖可能对非糖尿病患者有用，也许对接受胰岛素治疗的糖尿病患者也有用，以选择性降低肿瘤pH值并使肿瘤对热疗敏感。
