Curti B D, Urba W J, Alvord W G, Janik J E, Smith J W, Madara K, Longo D L
Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21701.
Cancer Res. 1993 May 15;53(10 Suppl):2204-7.
Interstitial pressure (IP) is a physiological variable that may have its greatest influence on the transport of high-molecular-weight therapeutic agents. IP in tumor nodules was measured in patients with metastatic melanoma or non-Hodgkin's lymphoma to determine the influence of this physiological variable on treatment outcome. The wick-in-needle technique was used to measure IP at time points before and after treatment with a variety of immunotherapy and chemotherapy regimens. Selected patients had IP measurements during chemotherapy or immunotherapy infusions. Ultrasound or computed tomography was used to evaluate the size of the studied lesions and their relationship to normal structures. The mean baseline IP in melanoma nodules (n = 22) and lymphoma nodules (n = 7) was 29.8 and 4.7 mm Hg, respectively (P = 0.013 for the difference between tumor types). In a subset of melanoma nodules for which IP had been measured before and after treatment, the IP increased significantly over time for nonresponding melanoma lesions from a baseline of 24.4 to 53.9 mm Hg after treatment (P = 0.005) and decreased in melanoma lesions that responded to treatment where the mean baseline and post-treatment IPs were 12.2 and 0 mm Hg, respectively (P = 0.001 for the difference in IP profiles between responding and nonresponding lesions). Six of seven lymphoma nodules responded completely to chemotherapy or radiation. The single nodule that did not respond had a baseline IP of 1 mm Hg that increased to 30 mm Hg after treatment. Tumor IP differs significantly between melanoma and non-Hodgkin's lymphoma. The changes in IP over time differ significantly between responding and nonresponding melanoma lesions. IP that increases during treatment appears to be associated with tumor progression in these tumor types.
间质压力(IP)是一种生理变量,可能对高分子量治疗药物的转运产生最大影响。对转移性黑色素瘤或非霍奇金淋巴瘤患者的肿瘤结节中的IP进行测量,以确定该生理变量对治疗结果的影响。采用针芯技术在多种免疫治疗和化疗方案治疗前后的时间点测量IP。部分选定患者在化疗或免疫治疗输注期间进行了IP测量。使用超声或计算机断层扫描评估所研究病变的大小及其与正常结构的关系。黑色素瘤结节(n = 22)和淋巴瘤结节(n = 7)的平均基线IP分别为29.8和4.7 mmHg(肿瘤类型之间的差异P = 0.013)。在一组治疗前后均测量了IP的黑色素瘤结节中,无反应的黑色素瘤病变的IP随时间显著增加,从基线的24.4 mmHg增加到治疗后的53.9 mmHg(P = 0.005),而对治疗有反应的黑色素瘤病变的IP则下降,其平均基线IP和治疗后IP分别为12.2和0 mmHg(反应性和无反应性病变之间IP曲线的差异P = 0.001)。7个淋巴瘤结节中有6个对化疗或放疗完全反应。唯一无反应的结节基线IP为1 mmHg,治疗后增加到30 mmHg。黑色素瘤和非霍奇金淋巴瘤之间的肿瘤IP有显著差异。反应性和无反应性黑色素瘤病变之间IP随时间的变化有显著差异。在这些肿瘤类型中,治疗期间升高的IP似乎与肿瘤进展相关。