针对端粒对肺癌可能是一种有效的治疗策略,根据研究
![Increased amplification frequency, copy number values and mRNA expression of TERT in NSCLC patients, and reduced tumor implantation in TERT-deficient mice upon lung tumor induction. Amplification frequency (A), copy number values (B) mRNA expression levels of TERT (C) and Pearson correlation of mRNA expression with copy number values of TERT (D) in lung tissues from NSCLC patients, and survival probability in NSCLC patients with high and low TERT expression (E) obtained from the Kaplan–Meier Plotter database. F Correlation between the expression of TERT and immune infiltrates in NSCLC patients from the TCGA using the TIMER 2.0 database. G, H Generation of Tert+/+ and G3 Tert−/− mice and protocol for the induction of Lewis Lung Carcinoma (LLC). G Heterozygous Tert+/− mice were crossed to obtain Tert+/+ and G1 Tert−/− mice, and successive crosses between G1 Tert−/− and then G2 Tert−/− were set to generate G3 Tert−/− mice. H 1 ×106 Lewis cells suspended in 100 µl of DMEM or equal volume of DMEM (controls) were injected via the tail vein of 10–12 weeks old Tert+/+ and G3 Tert−/− male mice on day 0 (D0). An in vivo follow follow-up of survival was carried out until sample collection on day 14 (D14). Kaplan–Meier survival curves (I), representative images of LLC-challenged Tert+/+ and G3 Tert−/− lungs and controls (H&E) (J), and quantification of lung tumor area (K, L) and foci (M) in Tert+/+ and G3 Tert−/− mice. N Representative Telomeric repeat amplification protocol (TRAP) using S-100 lung extracts from LLC-challenged Tert+/+ and G3 Tert−/− mice and controls, where protein concentration is indicated. Extracts were treated (+) or not (−) with RNase as a negative control (exposition time: 48 h). An internal control (IC) for PCR efficiency was also included and arrows indicate the lane used for quantification. O Quantification of Telomerase activity in lung extracts from LLC-challenged Tert+/+ and G3 Tert−/− mice and controls expressed in arbitrary units (a.u). P Lung tissue mRNA expression levels of Tert normalized to 18S expression in Tert+/+ and G3 Tert−/− mice. Data are expressed as mean ± SEM (the number of mice is indicated in each case). ***p < 0.001 (Dunn–Sidak test for multiple comparisons and Mann–Whitney or unpaired t tests to compare 2 independent groups). Survival was assessed by the Kaplan–Meier analysis, using the log Rank (Mantel–Cox) test). Credit: Cell Death & Differentiation (2023). DOI: 10.1038/s41418-023-01149-6 针对端粒对肺癌的可能是一个有效的治疗策略,根据研究](https://scx1.b-cdn.net/csz/news/800a/2023/targeting-telomeres-mi.jpg)
健康细胞只能把有限的次数在有机体的一生。相反,肿瘤细胞是不朽的:他们无限增殖和失控,这是癌症的定义特征。
端粒和端粒酶的研究人员小组CNIO(西班牙国家癌症研究中心),由Maria Blasco首次研究了针对治疗肺癌的可能性端粒结构,保护染色体的末端和无限期的条件决定了细胞的分裂能力。
解释的结果,研究人员在《华尔街日报》细胞死亡与分化,表明,事实上,针对端粒”可能是一种有效的治疗策略”对非小细胞肺癌,负责大部分肺癌患者的死亡率。Sergio Pineiro工作作为第一作者,接受者的博士后合同西班牙与癌症协会(AECC)。
“把永生从癌症细胞是一种治疗策略,尚未利用对抗癌症,”Maria Blasco说。
专注于肿瘤微环境
肺癌是癌症死亡的主要原因之一。当前的治疗和诊断晚期的长期无效意味着只有五分之一的病人存活超过5年。具体地说,非小细胞肺癌的85%负责肺癌相关的死亡。
现在的工作发表关注所谓的肿瘤微环境,这是一组细胞和肿瘤周围的因素在癌症的发展起着至关重要的作用和对治疗的反应。
研究人员分析了端粒功能失调的影响。同时,他们研究了端粒酶的作用缺乏在非小细胞肺癌的细胞微环境,端粒酶被修复端粒的酶。
端粒酶缺乏症
端粒是染色体末端的一种蛋白质结构位于。在每一个细胞分裂,端粒缩短,直到一定数量的分歧后,缩短变得过度,细胞停止分裂。这发生在健康的细胞,但不是大多数肿瘤细胞。
端粒酶表达在人类肿瘤的90%被重新激活。由于端粒酶的作用,肿瘤细胞的端粒维持一个最低功能长度,这允许他们将下去。
CNIO研究人员研究了发生了什么当他们引起了端粒酶赤字肺肿瘤微环境。他们还故意损害了他们的端粒,使用复合6-thio-dG。
“这是第一次的参与端粒酶和功能失调的端粒在肺肿瘤微环境调查,”塞吉奥Pineiro解释说,目前西班牙国家研究委员会(CSIC)在洛杉矶的里奥哈。
损坏的端粒抑制肿瘤
端粒酶缺乏症和功能失调的端粒延缓肿瘤进展。研究人员观察到减少肿瘤植入和肺血管化,同时增加的脆弱性肿瘤DNA损伤和细胞死亡。肿瘤细胞增殖和炎症也减少,免疫系统的抗肿瘤反应增强。
正如作者在写细胞死亡与分化,“我们地址第一次叔的含义(端粒酶)和功能失调的端粒在肺肿瘤微环境。我们的研究结果表明,针对端粒可能是一种有效的治疗策略非小细胞肺癌。"
更多信息:塞吉奥Pineiro-Hermida et al,端粒酶缺陷和功能失调的端粒在非小细胞肺癌肺肿瘤微环境影响肿瘤进展小鼠模型和patient-derived异种移植,细胞死亡与分化(2023)。DOI: 10.1038 / s41418 - 023 - 01149 - 6