Polymorphisms in EGFR Gene Predict Clinical Outcome in Unresectable Non-Small Cell Lung Cancer Treated with Radiotherapy and Platinum-Based Chemoradiotherapy

For non-small cell lung cancer (NSCLC), radiotherapy (RT) and platinum-based chemotherapy (CHT) are among the main treatment options. On the other hand, radioresistance and cytotoxic drug resistance are common causes of failure. The epidermal growth factor receptor (EGFR) plays an important role in radioresponse and therapy resistance. We hypothesized that single nucleotide polymorphisms (SNPs) in the EGFR gene might affect individual sensitivity to these treatments, and thus, therapy outcome and prognosis. The association between functional EGFR SNPs and overall (OS), locoregional recurrence-free (LFRS), and metastasis-free (MFS) survival was examined in 436 patients with unresectable NSCLC receiving RT and platinum-based CHTRT. In a multivariate analysis, the rs712830 CC homozygotes showed reduced OS in the whole group (p = 0.039) and in the curative treatment subset (p = 0.047). The rs712829 TT genotype was strongly associated with decreased LRFS (p = 0.006), and the T-C haplotype was a risk factor for locoregional recurrence in our patients (p = 0.003). The rs2227983 GG alone and in combination with rs712829 T was an indicator of unfavorable LRFS (p = 0.028 and 0.002, respectively). Moreover, significant independent effects of these SNPs on OS, LRFS, and MFS were observed. Our results demonstrate that inherited EGFR gene variants may predict clinical outcomes in NSCLC treated with DNA damage-inducing therapy.     

Induction of DNA-double-strand breaks by auger electrons from 99mTc complexes with DNA-binding ligands

The potential of certain Auger electron emitting nuclides for systemic radiotherapeutic applications has recently gained much attention. In particular, the ability of several nuclides, including 111In, 125I, and 123I, to induce DNA double-strand breaks (dsb), a good indicator of cytotoxicity, has been extensively studied. However, this ability has never previously been shown experimentally for 99mTc, which, besides the well-known gamma radiation that is used for diagnostic applications, also emits an average of 1.1 conversion electrons and 4 Auger or Coster-Kronig electrons per decay. Owing to the short range of Auger electrons, the radionuclide needs to be located very close to the DNA for dsb to occur. We synthesized two cationic 99mTcI-tricarbonyl complexes with pendant DNA binders, pyrene and anthraquinone. The X-ray crystal structures of the two complexes could be elucidated. Linear dichroism and UV/Vis spectroscopy revealed that the complex with pyrene intercalates DNA with a stability constant, K, of 1.1 x 10(6) M(-1), while the analogous complex with anthraquinone interacts with DNA in a groove-binding mode and has an affinity value of K=8.9 x 10(4) M(-1). We showed with phiX174 double-stranded DNA that the corresponding 99mTc complexes induce a significant amount of dsb, whereas non-DNA-binding [TcO4]- and nonradioactive Re compounds did not. These results indicate that the Auger electron emitter 99mTc can induce dsb in DNA when decaying in its direct vicinity and this implies potential for systemic radiotherapy with 99mTc complexes.     

一种应用于RTPS的轮廓线修改算法

放射医疗技术中,放射治疗计划系统对CT、MRI等医学影像数据进行处理,以获得体表、器官等医生所关注区域的轮廓,这是进行最终放射剂量计算的重要基础。文章针对自动提取或手动勾画的感兴趣区域的轮廓,提出并实现了一种修改算法。该算法可对自动提取不准确和勾画不正确的区域轮廓线进行修改,以达到用户预期的效果。算法实现方便,运行交互性好,能满足放射治疗计划系统的要求。     

Guanine and plasmid DNA binding of mono- and trinuclear fac-[Re(CO)3]+ complexes with amino acid ligands

We have synthesized and fully characterized four new complexes comprising the fac-[Re(CO)3]+ moiety and the ligands NH3, L-proline (Pro), or N,N-dimethylglycine (dmGly). The reaction of [Re(H2O)3(CO)3]+ with the two amino acids gives trinuclear complexes of general formula [Re(L)(CO)3]3 (where L = amino acid). We have studied the in vitro behavior of these compounds with guanine and DNA in order to understand whether the cytotoxicity exhibited by certain rhenium complexes based on the fac-[Re(CO)3]+ core is due to the formation of nucleobase complexes and inter- or intrastrand links between DNA bases. We have performed model studies with guanine and studied the structural effects induced by different rhenium(I) tricarbonyl complexes on PhiX174 plasmid DNA by electrophoretic methods. Our results show that rhenium complexes with two available coordination sites interact with plasmid DNA to form a stable adduct that is likely to involve two bases.     

基于Pylinac的放射治疗QA数字化分析系统

目的: 建立放射治疗直线加速器质量保证(Quality Assurance, QA)标准化体系和数字化分析系统是提升放疗水平和质量的有效途径. 方法: 基于Pylinac函数库, 采用Django框架和MySQL数据库结构搭建QA数字化分析系统, 并通过临床测试来评价该系统的稳定性与实用性. 结果: 放射治疗QA数字化分析系统不仅有利于监控及回顾分析直线加速器的运行状况, 而且有效减少医用直线加速器QA流程中计算分析的时间, 同时该系统还有助于放疗科新入职物理师快速熟悉QA流程. 结论: QA数字化分析系统在简化QA工作流程, 提高工作效率的同时, 更对放射治疗直线加速器的治疗体系中QA标准化起到进一步推进作用.     

用于放疗量传的照射量、空气比释动能和水吸收剂量量值体系比较

用照射量和空气比释动能校准的电离室进行剂量测量时,依据IAEA TRS 277报告,需要经历四级量值转换过程,不确定度也较大,但目前仍是国内使用的量值体系.我国正在建立60Co γ射线以及高能光子下的水吸收剂量基准装置并进行国际比对,之后将拥有水吸收剂量的量值复现的能力.在60Co γ射线参考辐射场和加速器高能X射线辐射场下,使用NE2571和NE2570/1A、PTW TW30013和PTW UNIDOS两套电离室剂量仪,分别按照277和398报告的要求计算并比较2种方法计算出的水吸收剂量值,从而验证了277报告和398报告的一致性.     

放疗病人信息管理系统的设计与实现

癌症是严重威胁人民生活健康的主要疾病。放射治疗的效果评价,放疗病人预后观察,影响放疗的危险因素探讨,都需要建立一个严密而完善的放射治疗病人资料的数据库。放疗病人计算机管理信息系统主要实现医院肿瘤放疗病人的相关信息管理。放疗病人计算机管理系统的实现,为肿瘤患者看病提供方便,也为医生和医学研究人员收集肿瘤患者资料提供了一个好的平台。     

子宫下段受累可能为Ⅰ期内膜癌辅助放疗的不良预后因素

目的　探讨子宫下段受累对Ⅰ期子宫内膜癌术后放疗患者的预后作用。方法　回顾性分析1999年1月至2012年12月在北京协和医院进行术后放疗的Ⅰ期子宫内膜癌患者265例，中位年龄53岁，病理类型主要为子宫内膜样腺癌(226例，85.3％)。根据病理结果是否有子宫下段受累分为两组：子宫下段受累组和子宫下段未受累组，比较两组患者的预后因素和临床治疗结果，并对其中的高危和高中危患者进行亚组分析。主要研究终点包括总生存率、无进展生存率、局部区域复发率、远处转移率和治疗失败率。使用Kaplan-Meier法统计生存率，不同组间生存率的比较使用Log-rank检验，使用Cox比例风险回归模型进行预后因素分析。结果　所有Ⅰ期内膜癌患者的5年总生存率和无进展生存率分别为92.8%和89.7%，5年局部区域复发率、远处转移率和治疗失败率分别为4.5%、6.4%和7.8%。单因素分析显示，子宫下段受累是影响总生存率和无进展生存率的相关因素（P= 0.015,0.035）。Cox比例风险回归模型显示，子宫下段受累组患者的总生存率和无进展生存率更低（P=0.041, RR=0.346, 95% CI: 0.125~0.959; P=0.041, RR=0.411, 95% CI: 0.175~ 0.963）。亚组单因素分析显示，在高危和高中危患者中，子宫下段受累是影响治疗失败率的相关因素（P=0.034）。结论　子宫下段受累可能是影响Ⅰ期内膜癌辅助放疗患者总生存率和无进展生存率的不良预后因素；在高危和高中危患者中，子宫下段受累主要与治疗失败的发生相关。     

Membrane Signaling Induced by High Doses of Ionizing Radiation in the Endothelial Compartment. Relevance in Radiation Toxicity

Tumor areas can now be very precisely delimited thanks to technical progress in imaging and ballistics. This has also led to the development of novel radiotherapy protocols, delivering higher doses of ionizing radiation directly to cancer cells. Despite this, radiation toxicity in healthy tissue remains a major issue, particularly with dose-escalation in these new protocols. Acute and late tissue damage following irradiation have both been linked to the endothelium irrigating normal tissues. The molecular mechanisms involved in the endothelial response to high doses of radiation are associated with signaling from the plasma membrane, mainly via the acid sphingomyelinase/ceramide pathway. This review describes this signaling pathway and discusses the relevance of targeting endothelial signaling to protect healthy tissues from the deleterious effects of high doses of radiation.     

Hedgehog Signaling in Prostate Cancer and Its Therapeutic Implication

Activation of Hedgehog (Hh) signaling is implicated in the development and progression of several tumor types, including prostate cancer, which is still the most common non-skin malignancy and the third leading cause of cancer-related mortality in men in industrialized countries worldwide. Several studies have indicated that the Hh pathway plays a crucial role in the development as well as in the progression of this disease to more aggressive and even therapy-resistant disease states. Moreover, preclinical data have shown that inhibition of Hh signaling has the potential to reduce prostate cancer invasiveness and metastatic potential. Clinical trials investigating the benefit of Hh inhibitors in patients with prostate cancer have recently been initiated. However, acquired drug resistance has already been observed in other tumor types after long-term Hh inhibition. Therefore, combining Hh inhibitors with ionizing radiation, chemotherapy or other molecular targeted agents could represent an alternative therapeutic strategy. In this review, we will highlight the role of Hh signaling in the development and progression of prostate cancer and summarize the different therapeutic applications of Hedgehog inhibition.