Dorward A M, Fancher K S, Duffy T M, Beamer W G, Walt H
The Jackson Laboratory, ME 04609, USA.
Br J Cancer. 2005 Nov 14;93(10):1137-43. doi: 10.1038/sj.bjc.6602840.
A photodynamic technique for human breast cancer detection founded upon the ability of tumour cells to rapidly accumulate the fluorescent product protoporphyrin IX (PpIX) has been applied to transgenic mouse models of mammary tumorigenesis. A major goal of this investigation was to determine whether mouse mammary tumours are reliable models of human disease in terms of PpIX accumulation, for future mechanistic and therapeutic studies. The haeme substrate 5-aminolevulinic acid (5-ALA) (200 mg kg(-1)) was administered to mouse strains that develop mammary tumours of various histological subtypes upon expression of the transgenic oncogenes HRAS, Polyoma Virus middle T antigen, or Simian Virus 40 large T antigen in the mammary gland. Early neoplastic lesions, primary tumours and metastases showed consistent and rapid PpIX accumulation compared to the normal surrounding tissues, as evidenced by red fluorescence (635 nm) when the tumours were directly illuminated with blue light (380-440 nm). Detection of mouse mammary tumours at the stage of ductal carcinoma in situ by red fluorescence emissions suggests that enhanced PpIX synthesis is a good marker for early tumorigenic processes in the mammary gland. We propose the mouse models provide an ideal experimental system for further investigation of the early diagnostic and therapeutic potential of 5-ALA-stimulated PpIX accumulation in human breast cancer patients.
一种基于肿瘤细胞快速积累荧光产物原卟啉IX(PpIX)能力的人类乳腺癌检测光动力技术已应用于乳腺肿瘤发生的转基因小鼠模型。本研究的一个主要目标是确定就PpIX积累而言,小鼠乳腺肿瘤是否是人类疾病的可靠模型,以便未来进行机制和治疗研究。将血红素底物5-氨基乙酰丙酸(5-ALA)(200 mg kg⁻¹)给予在乳腺中表达转基因癌基因HRAS、多瘤病毒中T抗原或猿猴病毒40大T抗原后会发生各种组织学亚型乳腺肿瘤的小鼠品系。与周围正常组织相比,早期肿瘤性病变、原发性肿瘤和转移灶显示出一致且快速的PpIX积累,当用蓝光(380 - 440 nm)直接照射肿瘤时,红色荧光(635 nm)证明了这一点。通过红色荧光发射在原位导管癌阶段检测小鼠乳腺肿瘤表明,增强的PpIX合成是乳腺早期致瘤过程的良好标志物。我们提出,这些小鼠模型为进一步研究5-ALA刺激的PpIX积累在人类乳腺癌患者中的早期诊断和治疗潜力提供了理想的实验系统。