乳腺癌患者细胞周期的进化假说:单个癌细胞的镶嵌期

P. Mehdipour
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引用次数: 1

摘要

细胞周期决定肿瘤的发生、发展和治疗方法。不受控制的细胞增殖和生长是恶性或良性肿瘤的关键特征。程序检查点通过相关障碍控制阶段的过渡。因此,平衡致癌过程可能会抑制进展并促进靶向治疗。方法:本研究在间期进行。通过免疫荧光和流式细胞术检测蛋白表达(PE),证实了荧光原位杂交法检测到花叶相(MPs)。结果:新的假设反映了双重和/或多阶段的存在,作为乳腺癌(BC)患者单细胞中的小克隆。根据这一发现,建立了一个具有适用比率值和不同MPs的模型,包括G1/S、S/G2和G1/S/G2,并伴有正常相(G1、S、G2)。不同周期蛋白组合E/B1和D1/E/B1与其他相关蛋白之间的信号拷贝数与相应的PE、双表达和三重共表达之间存在显著的调和行为。对于1号染色体,增益与正常信号的比值似乎是一个良好的预后,但对于3号染色体,该比值显著提高了生存率。结论:考虑MPs模型,易感-诊断-预测-预后-预防组合可能会导致CDKs抑制剂治疗的创新;也可用于BC和其他癌症的临床分类。
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Evolutionary Hypothesis in Cell Cycle of Breast Cancer Patients: Mosaic Phases in Single Cancer Cells
Introduction: Cell cycle shapes the initiation, progression and therapeutic approaches of neoplasms. An uncontrolled cell proliferation and growth are the key characteristics of either malignant or benign tumors. The programmed check points control the transition of phases through the related barriers. Therefore, balancing the carcinogenic processes may inhibit progression and facilitate a targeted-base therapy. Methods: The present study is performed in interphase. Detection of the Mosaic Phases (MPs) by Fluorescence In Situ Hybridization was confirmed by assaying the protein expression (PE) including immunofluorescence and flow cytometry. Results: The novel hypothesis reflects the presence of dual and/or multi-phases, as minor clones in single cells of breast cancer (BC) patients. This finding led to initiate a model with applicable ratio values and different MPs including G1/S, S/G2 and G1/S/G2, accompanied by normal phases (G1, S, G2). The remarkable harmonic behaviors between signal copy numbers and the corresponding PE, dual- and triple- co-expression between different cyclins combination including E/B1 and D1/E/B1 and the other involved proteins were observed. The ratio of gain to normal signals appeared to be a good prognosis for chromosome 1, but better survival was significantly obtained for this ratio in chromosome 3 Conclusion: The predisposing-diagnostic-predictive-prognostic-preventive panels may lead to innovate the CDKs inhibitor-based therapy by considering the MPs Model; and may also be considered for clinical classification, in BC and other cancers.
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