Machuca Damián, Chiarella Paula, Montagna Daniela, Dran Graciela, Meiss Roberto P, Ruggiero Raúl A
Laboratorio de Oncología Experimental, IMEX-CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Academia Nacional de Medicina de Buenos Aires, Argentina.
Medicina (B Aires). 2015;75(1):1-5.
Concomitant tumor resistance (CR) is a phenomenon in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. While former studies have indicated that T-cell dependent processes mediate CR in hosts bearing immunogenic small tumors, the most universal manifestation of CR induced by immunogenic and non-immunogenic large tumors had been associated with an antitumor serum factor that remained an enigma for many years. In a recent paper, we identified that elusive factor(s) as an equi-molar mixture of meta-tyrosine and ortho-tyrosine, two isomers of tyrosine that are not present in normal proteins and that proved to be responsible for 90% and 10%, respectively, of the total serum anti-tumor activity. In this work, we have extended our previous findings demonstrating that a periodic intravenous administration of meta-tyrosine induced a dramatic reduction of lung and hepatic metastases generated in mice bearing two different metastatic murine tumors and decreased the rate of death from 100% up to 25% in tumor-excised mice that already exhibited established metastases at the time of surgery. These anti-metastatic effects were achieved even at very low concentrations and without displaying any detectable toxic-side effects, suggesting that the use of meta-tyrosine may help to develop new and less harmful means of managing malignant diseases, especially those aimed to control the growth of metastases that is the most serious problem in cancer pathology.
伴随肿瘤抗性(CR)是一种现象,即荷瘤宿主对继发性肿瘤植入物的生长和转移具有抗性。虽然先前的研究表明,在携带免疫原性小肿瘤的宿主中,T细胞依赖性过程介导CR,但由免疫原性和非免疫原性大肿瘤诱导的CR的最普遍表现与一种抗肿瘤血清因子有关,该因子多年来一直是个谜。在最近的一篇论文中,我们确定了这种难以捉摸的因子是间酪氨酸和邻酪氨酸的等摩尔混合物,酪氨酸的这两种异构体不存在于正常蛋白质中,分别占血清总抗肿瘤活性的90%和10%。在这项工作中,我们扩展了我们之前的发现,证明定期静脉注射间酪氨酸可显著减少携带两种不同转移性小鼠肿瘤的小鼠产生的肺和肝转移,并将已在手术时出现已确立转移的肿瘤切除小鼠的死亡率从100%降至25%。即使在非常低的浓度下也能实现这些抗转移作用,并且没有显示出任何可检测到的毒副作用,这表明使用间酪氨酸可能有助于开发新的、危害较小的治疗恶性疾病的方法,特别是那些旨在控制转移生长的方法,而转移生长是癌症病理学中最严重的问题。