Tissue examination to monitor antiangiogenic therapy: a phase I clinical trial with endostatin.
Tissue examination to monitor antiangiogenic therapy: a phase I clinical trial with endostatin.
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发表时间：
2001-11
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通讯作者：
Christoph Mundhenke;James P. Thomas;George Wilding;Fred T. Lee;Fred Kelzc;Rick Chappell;Rosemary Neider;Linda A. Sebree;Andreas Friedl
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作者：
Christoph Mundhenke;James P. Thomas;George Wilding;Fred T. Lee;Fred Kelzc;Rick Chappell;Rosemary Neider;Linda A. Sebree;Andreas Friedl
目的
本研究的目的是确定血管生成抑制剂内皮抑素对肿瘤和伤口部位血管的影响。
实验设计
在一项I期剂量递增研究中，癌症患者每日接受人重组内皮抑素输注治疗。在治疗开始前和开始后8周获取肿瘤活检标本。通过用穿刺活检装置在手臂上制造皮肤伤口部位来评估非肿瘤组织中的血管形成。在间隔7天后对伤口部位进行第二次活检取样。这种连续活检程序在内皮抑素治疗开始前和开始后3周进行。测定肿瘤和皮肤伤口样本中的血管密度、内皮细胞动力学以及血管成熟度。通过电子显微镜检查肿瘤血管的超微结构。
结果
正如预期的那样，肿瘤的血管密度各不相同。皮肤创伤诱导产生含有高比例增殖内皮细胞的血管肉芽组织。未成熟血管的比例在肿瘤和伤口部位较高，在正常皮肤中较低。对于所测试的任何参数，在肿瘤和皮肤伤口的治疗前样本与治疗后样本之间均未检测到统计学上的显著差异。
结论
在内皮抑素治疗中，在所使用的剂量和治疗方案下，未发现与肿瘤样本中任何可识别的血管变化相关，也未干扰伤口愈合。
PURPOSE The purpose of this study was to determine the effect of the angiogenesis inhibitor endostatin on blood vessels in tumors and wound sites. EXPERIMENTAL DESIGN In a Phase I dose escalation study, cancer patients were treated with daily infusions of human recombinant endostatin. Tumor biopsies were obtained prior to and 8 weeks after initiation of treatment. Blood vessel formation in nonneoplastic tissue was evaluated by creating a skin wound site on the arm with a punch biopsy device. The wound site was sampled with a second biopsy after a 7-day interval. This sequential biopsy procedure was performed prior to and 3 weeks after initiation of endostatin treatment. Vascular density, endothelial cell kinetics, and blood vessel maturity were determined in tumor and skin wound samples. The ultrastructure of tumor blood vessels was examined by electron microscopy. RESULTS As expected, the tumors were of variable vascular density. Skin wounding induced a vascular granulation tissue containing a high percentage of proliferating endothelial cells. The proportion of immature blood vessels was high in tumors and in wound sites and low in normal skin. No statistically significant difference was detected between pretreatment and treatment samples of tumors and of skin wounds for any of the parameters tested. CONCLUSIONS Endostatin treatment was not associated with any recognizable vascular changes in tumor samples and did not perturb wound healing at the doses and the treatment schedule used.