HIF-1α及VEGF对乳腺癌肿瘤新生血管功能的调控及其超声光散射断层成像检测

Breast cancer is the most frequent cancer in Chinese women. Tumor angiogenesis associated with the diagnosis, treatment and prognosis of breast cancer patients. Hypoxia has been shown to be a common feature of a wide range of breast tumors. Hypoxia inducible factor-1(HIF-1α) activates vascular endothelial growth factor to promote angiogenesis and increase the potential to the invasive, metastasis and resistance to treatment. Diffuse optical tomography (DOT) could quantitatively measure total haemoglobin concentration (THC) and oxygen saturation, SO2)，a novel technique to detect and characterize angiogenesis. The quantitative measurement of THC and SO2 can be important to increase understanding of these abnormal microvascular functions..We highlight novel observation on breast cancer angiogenesis function on patients in vivo with DOT for imaging hemoglobin saturation in microvessel networks. By analysis the angiogenesis pathologies on breast cancer, we could understand its association with quantitative imaging and measurement of microvessel function. We would depict the level of HIF-1α and VEGF in tumors by reverse transcription polymerase chain reaction, Western blotting and immunohistochemistry. By comparison of benign to malignant breast tumors, we could further investigate the potential role of DOT as a mean of detection regulation of HIF-1α and VEGF on angiogenesis. Spectral imaging of microvasculature may yield measurements of microvessel hemoglobin saturation that can provide novel insights in a variety of breast cancer diseases processes. It could be great value on the management of breast cancer patients on the diagnosis, treatment and prognosis.

乳腺癌已成为中国女性恶性肿瘤发病之首。肿瘤新生血管与乳腺癌诊断、治疗、预后各环节密切相关。乳腺癌肿瘤内普遍存在缺氧，缺氧诱导因子-1α（ HIF-1α）可上调VEGF表达，与新生血管形成密切相关，同时参与肿瘤浸润、转移、治疗耐受。超声光散射断层成像（DOT）可定量测量肿瘤血红蛋白总量及氧饱和度，是研究肿瘤新生血管的崭新技术手段，其检测在体肿瘤乏氧及新生血管功能及调控的价值值得深入研究。.本研究拟采用组织病理及分子生物学方法，分析乳腺癌DOT功能成像的肿瘤微血管病理学基础；探讨光学参数与乳腺癌分级、分期、HIF-1α和VEGF表达等肿瘤生物学特性的相关性；评价DOT对肿瘤乏氧微环境新生血管功能的检测价值。研究首次将肿瘤低氧微环境和肿瘤新生血管结构功能变化的结合起来共同研究，从DOT检测角度探讨低氧及微血管结构功能变化的机制，为在体乳腺癌的功能评价平台建设做出有益探索。

乳腺癌已成为中国女性恶性肿瘤发病之首。肿瘤新生血管与乳腺癌诊断、治疗、预后各环节密切相关。乳腺癌肿瘤内普遍存在缺氧，缺氧诱导因子-1α（ HIF-1α）可上调VEGF表达，与新生血管形成密切相关，同时参与肿瘤浸润、转移、治疗耐受。超声光散射断层成像（DOT）可定量测量肿瘤血红蛋白总量，是研究肿瘤新生血管的崭新技术手段，其检测在体肿瘤乏氧及新生血管功能及调控的价值值得深入研究。..本研究采用组织病理及分子生物学方法，分析了乳腺癌DOT功能成像的肿瘤微血管病理学基础；探讨光学参数与乳腺癌分级、分期、HIF-1α和VEGF表达等肿瘤生物学特性的相关性；结果显示：乳腺浸润性导管癌的血红蛋白总量与其病变大小（P=0.000）、组织学分级（P<0.05）、淋巴结转移状态（P<0.01）、PR（P=0.000）显著相关，高血红蛋白总量的乳腺癌患者术后发生复发或转移几率增加(P=0.023)，提示DOT定量参数可术前无创评估肿瘤生物活性，为术前筛查高侵袭性的乳腺癌提供更多信息。血红蛋白总量与微血管密度呈直线相关，血管生成拟态对乳腺癌血供无显著影响。发生转移的乳腺癌组病灶血红蛋白总量与HIF-1α阳性表达相关；但与VEGF无统计学相关性。..上述研究结果显示了超声光散射断层成像的肿瘤新生血管病理学基础，提示THC可定量反映乳腺癌血供差异及机制，可能成为乳腺癌预后评估因子。研究将肿瘤低氧微环境和肿瘤新生血管结构功能变化的结合起来共同研究，从DOT检测角度探讨低氧及微血管结构功能变化的机制，为在体乳腺癌的功能评价平台建设做出有益探索。