2016年 40卷 第2期
2016, 40(2): 85-90.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.001
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摘要:
Objective Lung cancer cells associated with radioresistance are likely to give rise to local recurrence and distant metastatic relapse, but little is known about its underlying mechanisms. In the present paper, the effects of the HPV16 E6 and HPV16 E7 oncoprotein on the radiosensitivity of lung cancer cell lines were investigated. Methods The HPV16 E6 or HPV16 E7 oncoprotein was expressed by a transient transfection with pcDNA3-HPV16 E6 or pcDNA3-HPV16 E7 expression vector. Human lung cancer H2179 cells and mouse lung cancer Lewis cells were exposed to a γ-ray radiation source, cellular survival was evaluated by using a colony formation assay. The expression of HPV16 oncoproteins E6/E7, extracellular signal-regulated kinases 1/2(ERK1/2) and AKT signaling was determined by Western blot assay. VEGF secretion was determined by ELISA. Results Both HPV16 oncoproteins E6 and E7 significantly decreased radiosensitivity of H2179 cells, associated with a promotion of the ERK1/2 and AKT phosphorylation. A decrease of reactive oxygen species(ROS) and an increase of VEGF levels were observed in the cells expressing the HPV16 oncoproteins E6 and E7. Furthermore, a similar reduction of radiosensitivity mediated by the HPV16 oncoproteins E6 and E7 was also observed in a mouse lung cancer Lewis cells. Conclusion The findings indicate that the HPV16 oncoproteins E6 and E7 negatively affects susceptibility of lung cancer cells to radiotherapy via regulation of the ERK1/2 and Akt signaling pathway and VEGF expression.
2016, 40(2): 91-99.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.002
摘要:
Objective A nucleosomal protein, HMGB1, can be secreted by activated immune cells or passively released by dying cells, thereby amplifying rigorous inflammatory responses. In this study we aimed to test the possibility that radiation similarly induces cytoplasmic HMGB1 translocation and release. Methods Human skin fibroblast (GM0639) and bronchial epithelial (16HBE) cells and rats were exposed to X-ray radiation, and HMGB1 translocation and release were then assessed by immunocytochemistry and immunoassay, respectively. Results At a wide dose range(4.0-12.0 Gy), X-ray radiation induced a dramatic cytoplasmic HMGB1 translocation, and triggered a time- and dose-dependent HMGB1 release both in vitro and in vivo. The radiation-mediated HMGB1 release was also associated with noticeable chromosomal DNA damage and loss of cell viability. Conclusions Radiation induces HMGB1 cytoplasmic translocation and extracellular release through active secretion and passive leakage processes.
2016, 40(2): 100-105.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.003
摘要:
目的 评价广泛期小细胞肺癌(SCLC)化疗后接受胸部IMRT, 发生放射性肺炎(RP)的临床和剂量-体积因素。 方法 回顾性分析2007年至2012年接受化疗和IMRT的130例初治广泛期SCLC患者, 化疗方案以顺铂、依托泊甙方案为主, 放疗平均剂量为55.3 Gy(32~67 Gy)。RP采用常见不良反应事件评价标准(4.0版)进行评价, 分析放疗结束后2级及以上RP发生的危险因素。通过单因素和多因素统计学方法分析预测因子。 结果 全组中位随访时间37个月(4~66个月)。37例(28.5%)患者出现了≥2级的RP。单因素分析显示, 年龄和剂量学参数(双肺V5、V10、V20、V30、平均肺剂量、双肺体积)与RP显著性相关; 多因素分析显示, 只有双肺V5是≥2级RP的独立危险因素。 结论 多个临床和剂量学参数与RP的发生存在风险相关性, 尤其是双肺V5。对化疗有效的广泛期SCLC患者行胸部放疗时, 应综合考虑这些因素, 适当降低V5的体积。
2016, 40(2): 106-110.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.004
摘要:
目的 用国产11C-多功能合成模块经LOOP环法合成放射性药物11C-蛋氨酸(11C-MET), 与C-18柱固相法合成11C-蛋氨酸进行比较。 方法 对国产模块LOOP环法制备11C-MET的合成工艺进行探讨, 研究碱当量、溶剂效应及前体量等影响因素。 结果 LOOP环法制备11C-MET优化后的合成条件:前体量2~3 mg溶于NaOH溶液(2 mol/L), 碱当量5.6~11.5 eq, 加入乙醇100 μl, 室温反应。此条件下11C-MET的合成效率为(65.31±4.32)%(n=24, 11C-CH3I未校正效率), 产品的放化纯度>95%, 产量为(6.61±1.38) GBq。 结论 LOOP环法提高了11C-MET合成效率, LOOP环可以多次重复利用, 降低了生产成本, 提高了合成产量, 实现了稳定、全自动化合成11C-MET, 且产品能满足临床需求。
2016, 40(2): 111-114.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.005
摘要:
目的 比较99Tcm-MIBI SPECT/CT显像和钼靶X线对女性乳腺癌的诊断价值。 方法 女性患者83例, 先行99Tcm-MIBI胸部SPECT/CT早期显像和延迟显像, 并以延迟显像阳性为判定标准, 再行乳腺钼靶X线摄影, 并与最终的病理结果进行对照。 结果 延迟显像的阳性患者为52例(T/NT值>3.33), 阳性与阴性病灶的早期、延迟显像分别比较, 差异均有统计学意义, 且以延时2 h结果更为显著, 最终病理结果证实45例为恶性病灶。99Tcm-MIBI显像结果的灵敏度为93.33%、特异度为73.68%、阳性预测值为80.77%、阴性预测值为90.32%;而钼靶X线对于相同病灶的灵敏度、特异度分别为64.44%、73.68%, 阳性、阴性预测值分别为74.36%、63.63%。99Tcm-MIBI显像对乳腺癌诊断价值优于钼靶X线(χ2=4.11, P < 0.05), 但两种方法的一致性较差(Kappa=0.217, P < 0.05)。 结论 99Tcm-MIBI显像较之钼靶X线的结果判定更为客观, 而两种方法同时运用则能提高乳腺癌的检出率, 显著提高影像学对于乳腺癌的早期诊断。
2016, 40(2): 115-119.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.006
摘要:
目的 构建耐辐射奇球菌pprM基因缺失回补菌株, 为进一步研究PprM蛋白的功能奠定实验基础。 方法 设计并合成HA-pprM基因(HA为流感病毒血凝素)全长的引物, 以无突变的pGEX-6p-1-pprM载体为模板, PCR扩增出携带NdeⅠ酶切位点的HA-pprM基因全长, 经NdeⅠ酶切后, 与pRADK载体连接并转化大肠杆菌, 经培养、提取质粒及纯化后, 采用酶切鉴定以及基因测序方法确认插入序列的正确性; 采用CaCl2法将构建好的重组质粒pRADK-HA-pprM转化到耐辐射奇球菌pprM基因缺失的菌株中, 通过Western blot验证HA-PprM融合蛋白的表达。 结果 构建的重组质粒pRADK-HA-pprM经NdeⅠ酶切鉴定结果符合目的条带大小(438 bp), 测序结果显示插入的寡核苷酸序列及方向与预期的一致, Western blot结果显示HA-PprM融合蛋白的相对分子质量约为13000。 结论 笔者成功构建了重组质粒pRADK-HA-pprM, 为进一步研究与PprM蛋白相互作用的靶DNA的筛选奠定了良好的基础。
2016, 40(2): 120-124.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.007
摘要:
目的 基于Deauville标准探讨18F-FDG PET/CT在霍奇金淋巴瘤(HL)复发诊断中的应用价值。 方法 基于Deauville标准, 回顾性分析24例治疗结束后5~27个月, 临床可疑复发的HL患者, 对其18F-FDG PET/CT显像结果进行评分判断, 并与淋巴结活检和(或)骨髓活检病理结果进行对照分析。 结果 病理结果证实17例复发、3例淋巴结反应性增生、1例肺癌并纵隔淋巴结转移、3例未见明确复发。18F-FDG PET/CT诊断HL复发的灵敏度、特异度、阳性预测值、阴性预测值及准确率分别为100%、50%、85%、100%和87%。 结论 基于Deauville标准18F-FDG PET/CT在HL复发诊断中具有重要的临床应用价值。
2016, 40(2): 125-127,138.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.008
摘要:
目的 建立IRM-2小鼠再生障碍性贫血(AA)实验动物模型, 并检测其血液及相关免疫学指标。 方法 IRM-2小鼠经137Cs γ射线6 Gy照射后, 输入DBA/2小鼠的胸腺细胞, 建成免疫介导型AA模型。实验分3组, 即对照组、照射组和AA模型组, 于照射后第15天检测小鼠的血常规和免疫学指标。 结果 IRM-2小鼠AA模型组外周血WBC、RBC、骨髓有核细胞数和网织红细胞百分比分别为(2.38±0.53)×109/L、(8.22±0.21)×1012/L、(7.14±1.19)×106/股骨和(50.2±8.9)‰, 均低于对照组[(8.23±0.41)×109/L、(10.24±0.91)×1012/L、(16.5±1.61)×106/股骨和(76.2±9.7)‰]; IRM-2小鼠AA模型组免疫学指标中CD4+细胞比例[(8.91±2.55)%]低于对照组[(16.14±3.09)%], CD8+细胞比例[(13.55±2.12)%]高于对照组[(6.83±1.14)%]。IRM-2小鼠AA模型组外周血及免疫学指标与对照组比较, 差异均具有统计学意义。 结论 IRM-2小鼠AA动物模型的建立, 对AA的研究具有较好的应用价值。
2016, 40(2): 128-132.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.009
摘要:
Biomarkers, such as chromosome aberration and micronuclei assays, prove to be reliable for facilitating clinical diagnosis in radiation accidents. In a radiation accident in India, chromosomal aberration, γ-H2AX, as well as other blood markers, were detected in accidentally exposed victims. This multi-parametric approach aided in confirming that individuals had been exposed by ionizing radiation. However, doses were impossible to estimate because of a 30-day delay in accident awareness. Exposure dose for victims was estimated using a dose-response curve previously established. Dose estimation, blood cell depletion kinetics, and no appearance of prodromal symptoms suggested that doses of exposure were low. Hematologic investigation, sampling time, and chromosome aberration scoring were all proposed according to data from the victims exposed to 60Co. Finally, knowledge regarding chromosome aberration analysis and the importance of international co-operation and assistance should be shared from this accident.
Biomarkers, such as chromosome aberration and micronuclei assays, prove to be reliable for facilitating clinical diagnosis in radiation accidents. In a radiation accident in India, chromosomal aberration, γ-H2AX, as well as other blood markers, were detected in accidentally exposed victims. This multi-parametric approach aided in confirming that individuals had been exposed by ionizing radiation. However, doses were impossible to estimate because of a 30-day delay in accident awareness. Exposure dose for victims was estimated using a dose-response curve previously established. Dose estimation, blood cell depletion kinetics, and no appearance of prodromal symptoms suggested that doses of exposure were low. Hematologic investigation, sampling time, and chromosome aberration scoring were all proposed according to data from the victims exposed to 60Co. Finally, knowledge regarding chromosome aberration analysis and the importance of international co-operation and assistance should be shared from this accident.
2016, 40(2): 133-138.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.010
摘要:
Long non-coding RNAs(lncRNAs) are increasingly involved in diverse biological processes. Upon DNA damage, the DNA damage response(DDR) elicits a complex signaling cascade, which includes the induction of lncRNAs. LncRNA-mediated DDR is involved in non-canonical and canonical manners. DNA-damage induced lncRNAs contribute to the regulation of cell cycle, apoptosis, and DNA repair, thereby playing a key role in maintaining genome stability. This review summarizes the emerging role of lncRNAs in DNA damage and repair.
Long non-coding RNAs(lncRNAs) are increasingly involved in diverse biological processes. Upon DNA damage, the DNA damage response(DDR) elicits a complex signaling cascade, which includes the induction of lncRNAs. LncRNA-mediated DDR is involved in non-canonical and canonical manners. DNA-damage induced lncRNAs contribute to the regulation of cell cycle, apoptosis, and DNA repair, thereby playing a key role in maintaining genome stability. This review summarizes the emerging role of lncRNAs in DNA damage and repair.
2016, 40(2): 139-144.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.011
摘要:
人表皮生长因子受体2(HER2)亲和体分子因具有对靶组织亲和力高、特异性强、分子量小、制备简单、生物动力学特征良好等特点, 近年来在肿瘤分子影像方面的研究中显示出了较好的临床应用前景。放射性核素标记HER2亲和体分子探针不仅可以进行肿瘤受体显像及疗效评价, 还可以用于靶向治疗。笔者就目前放射性核素标记HER2亲和体分子探针精准诊疗的研究进展作简要综述。
人表皮生长因子受体2(HER2)亲和体分子因具有对靶组织亲和力高、特异性强、分子量小、制备简单、生物动力学特征良好等特点, 近年来在肿瘤分子影像方面的研究中显示出了较好的临床应用前景。放射性核素标记HER2亲和体分子探针不仅可以进行肿瘤受体显像及疗效评价, 还可以用于靶向治疗。笔者就目前放射性核素标记HER2亲和体分子探针精准诊疗的研究进展作简要综述。
2016, 40(2): 145-148, 158.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.012
摘要:
乳腺癌是全球女性发病率最高的恶性肿瘤, 为保证患者的生存率、减少术后并发症, 20世纪90年代用"腋窝前哨淋巴结活检术取代腋窝淋巴结清扫"的观点被提出并逐渐发展成为乳腺癌患者保乳术的常规方法。除腋窝前哨淋巴结外, 内乳前哨淋巴结的重要性同样不容忽视, 但是否将其作为前哨淋巴结活检的对象仍存在争议。面对目前形势, 核医学工作者做了大量研究, 在保证腋窝前哨淋巴结高显示率的同时尽可能提高内乳前哨淋巴结的显示率。笔者对近十年来国内外研究者在乳腺癌前哨淋巴结核素显像中的核素示踪剂、注射技术、显像仪器等方面的最新进展进行综述。
乳腺癌是全球女性发病率最高的恶性肿瘤, 为保证患者的生存率、减少术后并发症, 20世纪90年代用"腋窝前哨淋巴结活检术取代腋窝淋巴结清扫"的观点被提出并逐渐发展成为乳腺癌患者保乳术的常规方法。除腋窝前哨淋巴结外, 内乳前哨淋巴结的重要性同样不容忽视, 但是否将其作为前哨淋巴结活检的对象仍存在争议。面对目前形势, 核医学工作者做了大量研究, 在保证腋窝前哨淋巴结高显示率的同时尽可能提高内乳前哨淋巴结的显示率。笔者对近十年来国内外研究者在乳腺癌前哨淋巴结核素显像中的核素示踪剂、注射技术、显像仪器等方面的最新进展进行综述。
2016, 40(2): 149-153.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.013
摘要:
测定肿瘤细胞凋亡是早期评价肿瘤疗效的指标之一, 放射性核素凋亡显像是目前研究最为广泛、技术最为成熟的体内肿瘤细胞凋亡分子影像学检测技术, 能在活体内动态、无创地检测抗肿瘤治疗引起的细胞凋亡, 有助于肿瘤疗效的早期评判和预后分析, 其中特异性分子探针技术的研究开发是放射性核素凋亡显像的关键技术之一。笔者将目前有代表性的肿瘤细胞凋亡核素显像分子探针进行了总结。
测定肿瘤细胞凋亡是早期评价肿瘤疗效的指标之一, 放射性核素凋亡显像是目前研究最为广泛、技术最为成熟的体内肿瘤细胞凋亡分子影像学检测技术, 能在活体内动态、无创地检测抗肿瘤治疗引起的细胞凋亡, 有助于肿瘤疗效的早期评判和预后分析, 其中特异性分子探针技术的研究开发是放射性核素凋亡显像的关键技术之一。笔者将目前有代表性的肿瘤细胞凋亡核素显像分子探针进行了总结。
2016, 40(2): 154-158.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.014
摘要:
细胞核中的DNA被认为是电离辐射的首要靶点, 其损伤效应备受关注。近年来随着研究的不断深入, 发现线粒体也是电离辐射的重要靶点。线粒体作为人体唯一含有编码DNA的细胞器, 受到电离辐射后发生氧化应激不仅影响细胞的正常功能, 甚至导致细胞凋亡。笔者通过现有的研究数据总结了受到电离辐射后线粒体功能和形态的变化, 从而为辐射防护提供新的思路。
细胞核中的DNA被认为是电离辐射的首要靶点, 其损伤效应备受关注。近年来随着研究的不断深入, 发现线粒体也是电离辐射的重要靶点。线粒体作为人体唯一含有编码DNA的细胞器, 受到电离辐射后发生氧化应激不仅影响细胞的正常功能, 甚至导致细胞凋亡。笔者通过现有的研究数据总结了受到电离辐射后线粒体功能和形态的变化, 从而为辐射防护提供新的思路。
2016, 40(2): 159-164.
doi: 10.3760/cma.j.issn.1673-4114.2016.02.015
摘要:
miRNA是一类非编码的小RNA, 它主要利用碱基互补配对的方式与特异性靶基因信使RNA的3'-非翻译区结合, 通过降解靶RNA或抑制蛋白质的翻译合成, 从而实现对靶基因转录后水平的调控。放射治疗是治疗肿瘤的主要手段之一, 肿瘤的辐射生物效应对其放疗效果至关重要, 也是确定某肿瘤组织辐射敏感或辐射耐受的一个重要因素。研究证实, miRNAs通过影响DNA损伤修复、细胞周期检查点、凋亡、信号转导、肿瘤组织微环境等因素参与肿瘤放疗敏感性的调控, miRNAs为肿瘤放射治疗提供了新途径。
miRNA是一类非编码的小RNA, 它主要利用碱基互补配对的方式与特异性靶基因信使RNA的3'-非翻译区结合, 通过降解靶RNA或抑制蛋白质的翻译合成, 从而实现对靶基因转录后水平的调控。放射治疗是治疗肿瘤的主要手段之一, 肿瘤的辐射生物效应对其放疗效果至关重要, 也是确定某肿瘤组织辐射敏感或辐射耐受的一个重要因素。研究证实, miRNAs通过影响DNA损伤修复、细胞周期检查点、凋亡、信号转导、肿瘤组织微环境等因素参与肿瘤放疗敏感性的调控, miRNAs为肿瘤放射治疗提供了新途径。
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