亚太血浆肿瘤网络:三阴性乳腺癌研究进展

Q1 Medicine Clinical Plasma Medicine Pub Date : 2018-02-01 DOI:10.1016/j.cpme.2017.12.043
Xiaofeng Dai , Kostya Ostrikov
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引用次数: 0

摘要

在此,我们介绍亚太血浆肿瘤学网络,代表来自澳大利亚、中国、美国、韩国、马来西亚和新加坡的研究人员,并欢迎其他成员加入。三阴性乳腺癌(Triple negative breast cancer, TNBC)是三阴性乳腺癌的众多亚型之一,由于缺乏表面标志物表达和有效的靶向治疗,其预后最差,同时具有最高的侵袭性和癌性。从我们的工作中发现,等离子体活化介质(PAM)在选择性杀死tnbc方面更有效,并被应用于以下三方面的研究。第一部分:建立预测细胞对PAM反应的计算方程我们设计正交实验,分析PAM各参数对TNBC细胞的影响。在细胞数(C)、处理时间(T)、输出电压(U)、氦流量(F)、孔尺寸(A)、等离子体射流尾部到介质表面的距离(D1)、介质厚度(D2)等7个独立参数中,我们确定了PAM治疗TNBC疗效的4个主要影响因素。第二部分:内部等离子体治疗装置的开发和疗效比较我们开发了一种新的等离子体针状标点方法和装置,用于动物内部治疗,我们的体内实验证明了内部等离子体治疗相对于PAM和表面治疗的优势。第三部分:探讨PAM在TNBC治疗中的选择性机制PAM与其他BC亚型相比,具有选择性杀伤和抑制TNBC细胞迁移能力的能力。ALDH过表达的细胞群,代表癌症干细胞,对PAM治疗更敏感。在不同时间点对经PAM处理的TNBC和非TNBC细胞系进行高通量测序,发现一个在mRNA、miRNA、lncRNA和circRNA水平上整合数据的动态网络。通路分析巩固了我们假设的网络,即ALDH1介导的癌症干细胞信号传导对PAM治疗更敏感,导致癌症干细胞中比大部分肿瘤细胞更高比例的细胞死亡。我们目前的网络包括来自澳大利亚、中国、韩国、美国、新加坡和马来西亚的20多名活跃的教师和他们的研究人员和学生,我们衷心感谢他们。
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Introducing Asia-Pacific Plasma Oncology Network: Progress On Triple Negative Breast Cancer

Here we introduce the Asia-Pacific Plasma Oncology network representing researchers based in Australia, China, USA, Korea, Malaysia and Singapore and welcome other members to join.

Triple negative breast cancers (TNBC), among the many subtypes of such cancers, have the worst prognosis due to lack of surficial marker expression and effective targeted therapy as well as highest aggressiveness and cancer stemness. Plasma activated medium (PAM) was found, from our work, to be more effective in selectively killing TNBCs and was applied in the following three lines of studies.

Part 1: Establishment of computational equation predicting cells’ response to PAM

We designed orthogonal experiments to analyze the effects of various parameters of PAM in treating TNBC cells. Among 7 independent parameters, i.e., cell number (C), treatment time (T), output voltage (U), helium flow rate (F), well size (A), distance from the tail of plasma jet to medium surface (D1), and medium thickness (D2), we identified 4 primary influential factors that collectively determine the efficacy of PAM in treating TNBC.

Part 2: Internal plasma treatment device development and efficacy comparison

Novel plasma needle-like punctuation approach and device were developed for internal animal treatment, using which our in vivo experiments demonstrate the advantages of internal plasma treatment over PAM and surficial treatment.

Part 3: Exploration on mechanisms leading to PAM selectivity in TNBC treatment

PAM was found capable of selectively killing and inhibiting the migration ability of TNBC cells as compared with other BC subtypes. The cell cohort with ALDH over-expression, representing cancer stem cells, was found to be more sensitive to PAM treatment. High throughput sequencing on TNBC and non-TNBC cell lines treated with PAM under different time points revealed a dynamic network integrating data at mRNA, miRNA, lncRNA and circRNA levels. Pathway analyses consolidate our hypothetical network where ALDH1 mediated cancer stem cell signaling is more sensitive to PAM treatment that leads to higher fraction of cell death among cancer stem cells than bulk tumor cells.

Our current network involves more than 20 active faculty members from Australia, China, Korea, USA, Singapore and Malaysia with their researchers and students, and we sincerely thank all of them.

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Clinical Plasma Medicine
Clinical Plasma Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
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