Radiogenic lymphangiogenesis in the skin

Radiogenic lymphangiogenesis in the skin
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DOI:
10.2353/ajpath.2007.060589
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发表时间:
2007-07-01
影响因子:
6
通讯作者:
Helmbold, Peter
Helmbold, Peter
中科院分区:
医学2区
文献类型:
--
作者:
Jackowski, Susanne;Janusch, Matthias;Helmbold, Peter

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在标准化的人体方案中,研究了照射肿瘤环境中微血管变化的时间进程。40例初治乳腺癌患者在放疗后2~8周、11~14个月或17个月以上(皮肤当量剂量30~40GY),取照射皮肤及对照侧对照皮肤组织标本80例。11例接受淋巴清扫的黑色素瘤患者的22例活检组织作为对照。我们发现照射后1年样本中最小淋巴管密度(直径10微米)的增加主要是由于最小淋巴管密度的增加。我们的发现表明,在治疗后的第一年内发生了放射性淋巴管生成。放疗后2~8周,受照皮肤CD68(+)和血管内皮生长因子-C+细胞数显著升高。因此,我们的结果表明,侵袭巨噬细胞表达血管内皮生长因子-C可能是诱导放射性淋巴管生成的一条致病途径。
The time course of microvascular changes in the environment of irradiated tumors was studied in a standardized human protocol. Eighty skin biopsies from 40 patients with previously treated primary breast cancer were taken from irradiated skin and corresponding contralateral unirradiated control areas 2 to 8 weeks, 11 to 14 months, or 17+ months after radiotherapy (skin equivalent dose 30 to 40 Gy). Twenty-two biopsies of 11 melanoma patients who had undergone lymph node dissection were used for unirradiated control. We found an increase of total podoplanin(+) lymphatic microvessel density resulting mainly from a duplication of the density of smallest lymphatic vessels (diameter < 10 mu m) in the samples taken I year after radiation. Our findings implicate radiogenic lymphangiogenesis during the 1st year after therapy. The numbers of CD68(+) and vascular endothelial growth factor-C+ cells were highly elevated in irradiated skin in the samples taken 2 to 8 weeks after radiotherapy. Thus, our results indicate that vascular endothelial growth factor-C expression by invading macrophages; could be a pathogenetic route of induction of radiogenic lymphangiogenesis.