In this review, we focused on our studies of cancer dormancy in a murine B cell lymphoma and human breast cancer. Lifelong dormancy was induced in syngeneic mice by prior immunization to the idiotype of the tumor cell (TC) Ig before TC challenge. The mice maintained approximately 10(6) lymphoma cells in their spleen throughout their lifetime despite replication of the TCs at a reduced rate. Recurrences occurred randomly. Because of the balance between replication and cell death, we hypothesized that a similar balance might occur in long-term survivors of breast cancer when the risk of recurrences is very low. We developed a sensitive assay for circulating tumor cells (CTCs) which none were found in normal age-matched women. One third of patients, 7-22 years after mastectomy and without any evidence of disease, had CTCs. The half-life of these CTCs could be deduced from other studies as probably 2-3 hours. Hence, there was a precise balance between replication of TCs (presumably from micrometastases) and cell death. Therefore, a major population of clinically cured breast cancer patients have a chronic disease controlled by their own physiological mechanisms. We speculate on underlying mechanisms based both on studies in experimental models and clinical trials.

译文

:在这篇综述中,我们集中于对小鼠B细胞淋巴瘤和人类乳腺癌的癌症休眠研究。通过在TC攻击之前先对肿瘤细胞(TC)Ig的独特型进行免疫,可以在同系小鼠中终生休眠。尽管TCs的复制率降低了,但小鼠的一生中仍在脾脏中维持着约10(6)个淋巴瘤细胞。复发随机发生。由于复制和细胞死亡之间的平衡,我们假设当复发风险非常低时,长期存活的乳腺癌患者可能会发生类似的平衡。我们开发了一种循环肿瘤细胞(CTC)的灵敏检测方法,在正常年龄的女性中均未发现。乳房切除术后7-22年且无任何疾病证据的三分之一患者患有CTC。这些CTC的半衰期可以从其他研究中推断出来,大概为2-3小时。因此,在TC的复制(可能来自微转移)和细胞死亡之间存在着精确的平衡。因此,大部分临床治愈的乳腺癌患者患有受其自身生理机制控制的慢性疾病。我们基于实验模型和临床试验研究潜在的机制。

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