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,我们专注于对鼠b细胞淋巴瘤和人类乳腺癌中癌症休眠的研究。通过在TC攻击之前预先免疫肿瘤细胞 (TC) Ig的独特型,可以在同系小鼠中诱导终身休眠。尽管TCs的复制速度降低,但小鼠一生中仍在脾脏中维持约10(6) 个淋巴瘤细胞。复发是随机发生的。由于复制和细胞死亡之间的平衡,我们假设在复发风险非常低的情况下,乳腺癌的长期幸存者可能会出现类似的平衡。我们开发了一种针对循环肿瘤细胞 (ctc) 的灵敏检测方法,在正常年龄匹配的女性中均未发现。在乳房切除术后7-22年且没有任何疾病证据的患者中,有三分之一患有CTCs。这些ctc的半衰期可以从其他研究中推断为2-3小时。因此,TCs的复制 (可能来自微转移) 与细胞死亡之间存在精确的平衡。因此,临床治愈的乳腺癌患者的主要人群患有受自身生理机制控制的慢性疾病。我们根据实验模型和临床试验的研究推测潜在的机制。

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