术前放疗加手术与单纯手术治疗喉癌的临床疗效比较

目的:比较术前放疗加手术与单纯手术治疗喉癌的临床疗效。方法:选择2005年8月至2007年1月在我院治疗的喉癌患者122例为研究对象。随机进行分组,观察组(术前放疗加手术组)60例,对照组(单纯手术组)62例,比较两组患者治疗后的效果。结果:观察组Ⅰ期、Ⅱ期喉癌患者5年生存率为88.9%,与对照组比较差异不明显,P>0.05;Ⅲ期、Ⅳ期喉癌患者5年生存率为62.5%,显著高于对照组,P<0.05。结论:对于肿瘤分期为Ⅰ期及Ⅱ期的患者来说,术前放疗并不能显著提高患者的5年生存率,而Ⅲ期、Ⅳ期患者术前放疗能够显著提高生存率。     

早期三阴乳腺癌改良根治术后放疗及预后相关因素分析

目的 分析研究早期（T_1~2N₁M₀）三阴乳腺癌患者改良根治术后放疗及预后危险因素,为该分期三阴乳腺癌患者临床治疗方案的选择提供依据。方法 回顾性分析2006年1月至2011年10月大连医科大学附属二院收治的术后病理分期为T_1~2N₁M₀三阴乳腺癌患者共87例。根据术后是否放疗将患者分为放疗组（53例）,未疗组（34例）。Kaplan-Meier单因素分析术后放疗、年龄、月经、组织学分级、脉管癌栓、T分期、淋巴结阳性数及转移率、手术方式、Ki-67指数等对患者5年局部区域复发率（LRR）、远处转移（DM）率、无复发生存（RFS）率、总生存（OS）率预后的影响。结果 术后放疗组与未疗组5年LRR（9.4%和15.2%）和RFS（81.3%和66.7%）比较,差异有统计学意义（χ²=8.073、12.789,P<0.05）,而DM及OS两组比较差异无统计学意义（P>0.05）。单因素分析结果显示,放疗、淋巴结转移率、年龄、Ki-67指数是影响5年LRR的危险因素（P<0.05）;脉管癌栓、淋巴结转移率是影响 5 年 DM 的危险因素（P<0.05）;放疗、脉管癌栓、淋巴结转移率和Ki-67指数是影响5年 RFS 的危险因素（P<0.05）。多因素分析结果显示,放疗和淋巴结转移率是影响5年LRR的独立危险因素（HR=0.279、5.277 P<0.05）;脉管癌栓是影响5年DM的独立危险因素（HR=2.313, P<0.05）;放疗、脉管癌栓和淋巴结转移率是影响5年RFS 独立危险因素（HR=0.378、2.35、5.084, P<0.05）。结论 术后放疗可以改善T_1~2N₁M₀期三阴乳腺癌患者的局部控制率,但对5年的DM和OS影响不大。术后放疗、淋巴结转移率、脉管癌栓、Ki-67指数、年龄与早期三阴乳腺癌预后相关。     

Liquid biopsy in lymphoma: Molecular methods and clinical applications

In this article, we broadly review the application of cfDNA analysis to the diagnosis and management of lymphoma. We introduce the advantages of cfDNA measurement over conventional tissue biopsy and describe how cfDNA may be utilized for both genotyping and detection of minimal residual disease. First, we discuss genotyping, beginning with differences in identifying mutations from the blood plasma vs. from circulating cells. We review the technical distinctions between PCR- and NGS-based assays and describe two important applications of NGS-based cfDNA tests, namely the identification of resistance mutations and classification of disease subtype. We discuss difficulties in genotyping diseases with low burden of tumor cells and the application of cfDNA assays in these contexts. Second, we describe the utility of ctDNA measurement in assessing MRD. We cover recent advances in the assessment of pre-treatment disease burden as a prognostic biomarker, detection of molecular response to therapy, and early detection of relapsing disease. Third, we explore select emerging areas of research in ctDNA technologies that show promise in boosting the performance of existing ctDNA-based assays. These include cell-free DNA fragment structure analysis or ‘fragmentomics’, epigenetic modifications, and novel circulating analytes such as tumor-educated platelets and extracellular vesicular DNA. We also discuss alternative analytes to blood plasma for tumor detection, such as urine, saliva, and stool. Finally, we present a case that highlights potential applications of ctDNA approaches to the management of patients with lymphoma, while also defining important prerequisite advances before this can be fully realized. We close with a look to the future of cfDNA applications, outlining one potential timeline and path forward towards routine clinical application.     

三维适形放疗治疗晚期腹部恶性肿瘤的疗效观察及近期疗效相关因素分析

[目的]观察三维适形放疗治疗局部晚期腹部恶性肿瘤的疗效,并分析影响近期疗效的相关因素。[方法]对38例晚期腹部恶性肿瘤患者进行三维适形放疗,单次剂量300～400cGy,共10—12次,每日或隔日照射1次,每周5次或3次,总剂量3000～4800cGy,放疗结束后进行疗效评价及近期疗效相关因素分析。[结果]近期疗效：总有效率（CR＋PR＋SD）为63．2％;远期疗效：3、6、12个月生存率分别为为63．2％、39．5％和34．2％,中位生存期4个月;多因素分析放疗总剂量是影响腹部恶性肿瘤三维适形放疗近期疗效的相关因素,具有统计学意义（P〈0．05）。[结论]三维适形放疗能够缩瘤减症,提高生存质量。放疗总剂量是影响腹部恶性肿瘤三维适形放疗近期疗效的相关因素。     

X射线照射诱导鼻咽癌细胞hMSH2的表达

目的研究X射线照射对鼻咽癌CNE-1细胞错配修复基因hMSH2表达的影响,探讨放射损伤后肿瘤细胞的DNA修复机制。方法应用逆转录-PCR(RT-PCR)、免疫细胞化学及蛋白免疫印迹(Western blot)方法,检测X射线照射后对照组和实验组(照射总剂量分别为0Gy和10Gy)细胞中hM-SH2基因mRNA及蛋白表达。结果实验组细胞hMSH2基因mRNA及蛋白表达在照射终止后逐渐上调,其表达较对照组显著增强(P<0.01)。结论X射线照射可诱导鼻咽癌细胞hMSH2的表达,有助于放射损伤后肿瘤细胞DNA修复,这可能是肿瘤放疗敏感性降低的原因之一。     

HPD overexpression predicts poor prognosis in breast cancer

BackgroundThe enzyme, 4-hydroxyphenylpyruvate dioxygenase (HPD), is critical to tyrosine metabolism; its deficiency can cause tyrosinemia. However, its precise contribution to tumorigenesis is unclear. Here, we investigated the correlation between HPD expression and prognosis in patients with breast cancer.Methods145 breast cancer specimens were selected to analyze HPD protein expression by immunohistochemistry and evaluate its relationship to patients’ clinicopathological features. HPD localization was confirmed in MCF-7 and MDA-MB-231 breast cancer cells, using immunofluorescence staining. The expression of HPD protein was detected in breast cancer and cancer-adjacent normal tissues using Western blot analysis. Survival rates were calculated by the Kaplan–Meier method.ResultsWe found that HPD protein was mainly located in the cytoplasm/nucleoli/perinucleus in breast cancer cells, as shown by immunofluorescence staining in MCF-7 and MDA-MB-231 cells, and immunohistochemistry in breast cancer and adjacent normal tissues (HPD protein expression—breast cancer: 46.9% [68/145], ductal carcinoma in situ [DCIS]: 22.6% [12/53], and normal tissues: only 4.8% [2/42]). Similarly, the Western blot results further confirmed the increased expression of HPD in breast cancer compared with cancer-adjacent normal tissues (P < 0.05). HPD expression level was positively correlated with histological grade and clinical stage, and inversely correlated with 10-year overall survival (OS) rates, in patients with breast cancer. Among patients with breast cancer, those with high HPD expression had worse OS rates than those with low HPD expression. Additionally, when patients were subgrouped by disease stage or grade, those with high HPD expression had worse OS rates than those with low HPD expression for each respective stage or grade.ConclusionsOur findings indicate that HPD may be a useful prognostic predictor, and a potential therapeutic target for patients with breast cancer.     

局部晚期非小细胞肺癌手术与非手术治疗对比研究

目的:局部晚期非小细胞肺癌(locally advanced non-small cell lung cancer,LANSCLC)放化综合治疗已是共识,手术介入是否致临床获益报道不一,本研究目的是评价手术治疗在综合治疗中的作用。方法:将71例患者据治疗方法分为A组:手术+放化疗组(37例)、B组:放疗+化疗组(34例)。采用Kaplan-Meier和Log-Rank方法进行生存分析,RTOG标准评价急性反应和晚期损伤。结果:中位随访25.5个月,A组中位总生存时间34.6个月,中位无进展生存时间22.3个月,1、2、3年生存率分别为95%、78%、34%;B组近期有效率52.9%,中位总生存时间为16.5个月,1、2、3年生存率分别为76%、28%、10%。A组在生存时间及生存率方面均有明显优势(P<0.05)。化疗不良反应两组相较差异无显著性(P>0.05)。放疗主要不良反应为放射性食管炎及放射性肺炎。手术并未明显增加放疗不良反应发生率及发生程度(P>0.05)。术后患者半数以上2年内出现疾病进展,疾病进展原因主要为远处转移,转移率76.2%。结论:LANSCLC治疗要以综合治疗为主,手术治疗可使生存受益,并延长无进展生存时间以及生存时间,并未增加放化疗不良反应。     

Efficacy and Safety of Rezivertinib (BPI-7711) in Patients With Locally Advanced or Metastatic/Recurrent EGFR T790M-Mutated NSCLC: A Phase 2b Study

IntroductionRezivertinib (BPI-7711) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) targeting both EGFR-sensitizing mutations and EGFR T790M mutation. This study aimed to evaluate the efficacy and safety of rezivertinib in patients with locally advanced or metastatic/recurrent EGFR T790M-mutated NSCLC.MethodsPatients with locally advanced or metastatic/recurrent NSCLC with confirmed EGFR T790M mutation who progressed after first-/second-generation EGFR TKI therapy or primary EGFR T790M mutation were enrolled. Patients received rezivertinib at 180 mg orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival, and safety. This study is registered with Clinical Trials.gov (NCT03812809).ResultsA total of 226 patients were enrolled from July 5, 2019, to January 22, 2020. By the data cutoff date on January 24, 2022, the median duration of follow-up was 23.3 months (95% confidence interval [CI]: 22.8–24.0). The ORR by blinded independent central review was 64.6% (95% CI: 58.0%–70.8%), and DCR was 89.8% (95% CI: 85.1%–93.4%). The median duration of response was 12.5 months (95% CI: 10.0–13.9), and median PFS was 12.2 months (95% CI: 9.6–13.9). The median overall survival was 23.9 months (95% CI: 20.0–not calculated [NC]). Among 91 (40.3%) patients with central nervous system (CNS) metastases, the median CNS PFS was 16.6 months (95% CI: 11.1–NC). In 29 patients with more than or equal to one brain target lesion at baseline, the CNS ORR and CNS DCR were 69.0% (95% CI: 49.2%–84.7%) and 100% (95% CI: 88.1%–100%), respectively. Time to progression of CNS was 16.5 months (95% CI: 9.7–NC). Of 226 patients, 188 (83.2%) had at least one treatment-related adverse event, whereas grade more than or equal to 3 occurred in 45 (19.9%) patients. No interstitial lung disease was reported.ConclusionsRezivertinib was found to have promising efficacy and favorable safety profile for patients with locally advanced or metastatic/recurrent NSCLC with EGFR T790M mutation.     

基因芯片筛选榄香烯乳增强肺腺癌A549 细胞放射敏感性相关基因

目的 利用基因芯片筛选榄香烯乳增加肺腺癌A549细胞放射敏感性的相关基因.方法 MTT法检测榄香烯乳对A549细胞的生长抑制效应,求得,IC50值;克隆形成实验检测榄香烯乳对肺腺癌A549细胞放射增敏作用;实验分为照射组及榄香烯乳联合照射组,寡核苷酸基因芯片筛选两组细胞的差异表达基因;RT-PCR法对差异表达基因进行验证.结果 榄香烯乳对A549细胞24 h的IC50值为120 mg/L;10 mg/L榄香烯乳对A549细胞有放射增敏作用,放射增敏比SERDDO、SERDq为1.54±0.20和1.43±0.15.基因芯片共检测出差异表达基因122个,上调基因89个,基因33个,其功能参与维持细胞结构、细胞代谢、增殖分化、信号传导、物质转运、细胞凋亡、DNA修复和免疫应答等.RT-PCR结果:上调基因Egr-1及下调基因CyclinDl表达与基因芯片结果一致.结论 榄香烯乳对肺腺癌A549细胞的放射增敏作用机制是多基因参与、协同作用的结果,对于新发现的差异基因的进一步研究,将有助于发现榄香烯乳对肺癌A549细胞放射增敏的新靶点.

Abstract：

Objective To screen radiosensitizing-related genes mediated by elemene in lung adenocarcinoma A549 cells by using gene chip. Methods MTT test was used to calculate the IC50 of elemene. ①The effect of radiosensitivity was detected by colony forming assay. A549 cells were divided into 2 groups: radiation group and radiation + elemene group. Oligonucleotide chip was used to screen the gene expression changes of A549 cells from these 2 groups. The up-regulated gene Egr-1 and the down-regulated gene CyclinDl were selected to undergo RT-PCR so as to confirm the reliability of the result. Results MTT test showed the elemene inhibited the proliferation of the A549 cells dose-dependently. The IC50 value of elemene on the A549 cells was 120 mg/L. ②10 mg/L elemene had radiosensiting effect on A549 cells.The values of SERDO and SERDq obtained from the survival curve were (1.54±0. 20) and (1.43±0. 15 )respectively. Gene chip screened 122 differentially-expressed genes, including 89 up-regulated genes and33 down-regulated genes. ③These altered genes could be related to cell structure, substance metabolism,cell proliferation, cell differentiation, signal transduction, material transport, DNA repair, apoptosis,immune response and so forth. The RT-PCR results of Egr-1 and Cyclin D1 were consistent with the genenchip analysis.Conclusions The mechanism of elemene enhancing the radiosensitivity of lung adenoearcinoma A549 cells is the result of participation and collaboration of multiple genes. Further study of the newly-discovered differentially-expressed gene helps find out new radiosensitizational targets of elemene.