血清TAP、TFF3与晚期胃癌患者含奥沙利铂化疗方案敏感性和预后的关系

摘要 目的：探讨血清肿瘤异常蛋白（TAP）、三叶因子3（TFF3）与晚期胃癌患者应用含奥沙利铂化疗方案敏感性和预后的关系。方法：选择2017年1月至2020年1月河北大学附属医院收治的115例晚期胃癌患者,所有患者接受含奥沙利铂化疗方案治疗,根据疗效分为敏感组（47例）和耐药组（68例）。化疗前检测血清TAP、TFF3水平,受试者工作特征（ROC）曲线分析TAP、TFF3预测晚期胃癌患者接受含奥沙利铂化疗疗效的价值。治疗后随访,Wilcoxon检验不同血清TAP、TFF3表达下晚期胃癌患者中位OS时间差异。结果：耐药组血清TAP、TFF3水平高于敏感组（P＜0.05）。TAP、TFF3预测晚期胃癌患者含奥沙利铂化疗耐药的曲线下面积分别为0.717、0.690,联合TAP和TFF3预测晚期胃癌患者含奥沙利铂化疗耐药的曲线下面积为0.801,高于单独TAP、TFF3单独检测。随访期间失访2例,死亡54例,高水平TAP、高水平TFF3晚期胃癌患者中位OS时间短于低水平TAP、低水平TFF3晚期胃癌患者（P＜0.05）。结论：对含奥沙利铂化疗耐药的晚期胃癌患者血清TAP、TFF3水平显著增高,高水平TAP、TFF3晚期胃癌患者中位OS时间较短,联合检测血清TAP和TFF3可预测晚期胃癌患者化疗反应性和预后。     

免疫检查点抑制剂联合抗血管生成二线治疗晚期食管癌患者疗效及肿瘤标志物表达、预后生存期的影响

摘要 目的：研究信迪利单抗与阿帕替尼在晚期食管癌二线治疗中的应用效果。方法：根据随机数字表法将2019年1月～2022年1月本院收治的70例食管癌患者分为对照组与观察组,每组各35例,对照组给予阿帕替尼治疗,观察组给予信迪利单抗与阿帕替尼联合治疗,观察两组患者的客观缓解率（ORR）、疾病控制率（DCR）,并在治疗前后利用酶联免疫吸附法检测其糖类抗原50（CA-50）、糖类抗原199（CA199）、癌胚抗原（CEA）、鳞癌抗原（SCC）水平;随后通过随访记录两组患者的预后生存期,并建立多因素Logistic模型分析影响患者达到中位OS、PFS的独立危险因素。结果：与对照组比较,观察组ORR、DCR率较高（P＜0.05）。与对照组相比,治疗后观察组血清CA50、CA199、CEA、SCC水平较低（P＜0.05）。与对照组比较,观察组中位OS、PFS较长（P＜0.05）。多因素Logistic分析结果显示,治疗方法、CA50、CA199、CEA、SCC是影响食管癌预后生存期的独立危险因素（P＜0.05）。结论：利用免疫检查点抑制剂与抗血管生成药物对晚期食管癌患者开展二线治疗,不仅能降低血清中的肿瘤标志物浓度,还能延长患者的预后生存期,治疗效果较为显著。     

Methylation of death-associated protein kinase is associated with cetuximab and erlotinib resistance

Anti-EGFR therapy is among the most promising molecular targeted therapies against cancer developed in the past decade. However, drug resistance eventually arises in most, if not all, treated patients. Emerging evidence has linked epigenetic changes, such as DNA methylation at CpG islands, to the development of resistance to multiple anticancer drugs. In addition, genes that are differentially methylated have increasingly been appreciated as a source of clinically relevant biomarker candidates. To identify genes that are specifically methylated during the evolution of resistance to anti-EGFR therapeutic agents, we performed a methylation-specific array containing a panel of 56 genes that are commonly known to be regulated through promoter methylation in two parental non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) cell lines and their resistant derivatives to either erlotinib or cetuximab. We found that death-associated protein kinase (DAPK) was hypermethylated in drug-resistant derivatives generated from both parental cell lines. Restoration of DAPK into the resistant NSCLC cells by stable transfection re-sensitized the cells to both erlotinib and cetuximab. Conversely, siRNA-mediated knockdown of DAPK induced resistance in the parental sensitive cells. These results demonstrate that DAPK plays important roles in both cetuximab and erlotinib resistance, and that gene silencing through promoter methylation is one of the key mechanisms of developed resistance to anti-EGFR therapeutic agents. In conclusion, DAPK could be a novel target to overcome resistance to anti-EGFR agents to improve the therapeutic benefit, and further evaluation of DAPK methylation as a potential biomarker of drug response is needed.     

从国际非专利名称纵观全球生物药发展

生物药(bio-therapeutics)是指采用生物技术制备的、临床上用于疾病治疗的大分子生物制品,具有结构复杂、异质性高等特点,科学严谨的生物药通用名命名,是区分生物药物质基础的主要依据,也是药品生命周期管理的重要基础。世界卫生组织(World Health Organization,WHO)协调建立的国际非专利名称(International Nonproprietary Names,INN)是全球药物命名的标准化体系。从INN的起源,以及生物药INN的类别、发生与发展为主线,以较为详实的数据统计和分析,呈现了全球生物药的衍化进程,从不同的角度纵览生物药技术发展历程,对生物药的研发设计、技术标准及监管策略的考量均具有一定的参考意义。     

解毒颗粒联合阿帕替尼治疗中晚期肝癌的回顾性研究

目的:评估解毒颗粒联合阿帕替尼治疗中晚期肝癌患者的疗效及其不良反应。方法:对2018年12月至2019年6月收治于海军军医大学第一附属医院口服解毒颗粒联合阿帕替尼的27例肝癌患者的临床资料进行回顾性研究。无法切除或复发的中晚期肝癌患者被纳入研究,给予解毒颗粒联合阿帕替尼治疗直至疾病进展或不可耐受其毒副反应,随访观察治疗效果、生存期、炎症因子指标及不良反应。结果:治疗后完全缓解(CR)4例(14.81%),部分缓解(PR)4例(14.81%),稳定(SD)8例(29.63%),进展(PD)11名患者(40.74%),疾病控制率(DCR)为59.26%(16/27),客观缓解率(ORR)为29.63%(8/27)。中位无进展生存期(PFS)为3.630个月,中位总生存期(OS)为13.667个月。常见的不良反应是高血压59.26%(16/27)、蛋白尿59.26%(16/27)、腹泻74.07%(20/27)以及手足综合征62.96%(17/27)。治疗后炎症因子指标中C反应蛋白、白介素2水平下降,存在统计学差异(P0.05)。结论:解毒颗粒联合阿帕替尼治疗中晚期肝癌安全、有效,可降低患者炎症反应,不良反应可耐受。     

腹腔镜辅助胃癌D2根治术联合胃背侧系膜近胃端完整系膜切除术对进展期胃癌患者肠黏膜屏障功能和腹腔微转移的影响

摘要 目的：探讨腹腔镜辅助胃癌D2根治术联合胃背侧系膜近胃端完整系膜切除术对进展期胃癌（AGC）患者肠黏膜屏障功能和腹腔微转移的影响。方法：选取2016年12月～2018年12月我院收治的105例AGC患者,按随机数字表法分为对照组（n=52）和实验组（n=53）,分别施行腹腔镜辅助胃癌D2根治术、腹腔镜辅助胃癌D2根治术联合胃背侧系膜近胃端完整系膜切除术。观察两组手术情况（淋巴结清扫数量、手术时间、术中出血量、近切缘距离）、胃肠功能恢复指标（肛门排气时间、经口进食时间、肠鸣音恢复时间）、并发症、住院时间及术前、术后1 d、3 d、7 d肠黏膜屏障功能[尿乳果糖/甘露醇（L/M）、血清二胺氧化酶（DAO）]、气腹后、关腹前腹腔微转移指标[多巴胺脱羧酶（DDC）、癌胚抗原（CEA）],并于术后12个月随访两组复发率。结果：实验组术中出血量少于对照组（P＜0.05）;两组经口进食时间、肛门排气时间、住院时间、肠鸣音恢复时间比较无差异（P＞0.05）;术前、术后1 d、3 d、7 d两组血清DAO水平、尿L/M比较无差异（P＞0.05）;关腹前实验组腹腔冲洗液DDC、CEA水平低于对照组（P＜0.05）;两组并发症总发生率比较,差异无统计学意义（P＞0.05）;术后12个月随访,实验组和对照组各失访2例,实验组复发率3.92%（2/51）低于对照组20.00%（10/50）（P＜0.05）。结论：腹腔镜辅助胃癌D2根治术联合胃背侧系膜近胃端完整系膜切除术治疗AGC,能有效降低术中出血量,恢复胃肠功能,减少腹腔微转移及术后复发,且未增加肠黏膜屏障功能损伤,安全性高。     

High-dose neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery in potentially-resectable stage IIIA-N2 NSCLC. A multi-institutional retrospective study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)

BackgroundThe optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined.AimTo compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC).MethodsRetrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014.Results47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. “not reached” (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS.ConclusionsCompared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients.     

Synthesis and evaluation of 18F labeled crizotinib derivative [18F]FPC as a novel PET probe for imaging c-MET-positive NSCLC tumor

c-MET-positive NSCLC is an important subtype accounting for about 5%~22% of lung cancer. NSCLC patients with activating c-MET are intensively sensitive to c-MET selective receptor tyrosine kinase (RTK) inhibitors, so we aimed to develop a specific PET probe targeting to c-MET-positive NSCLC for potential patients screened by PET/CT. Herein, PET tracer ¹⁸F-radiolabeled crizotinib derivative ([¹⁸F]FPC) was successfully achieved through a simple one-step ¹⁸F-labeling method. [¹⁸F]FPC PET imaging on c-MET-positive (as well as blocking group) and negative NSCLC models were further evaluated, and results showed that [¹⁸F]FPC was effective as a PET imaging probe that targeted c-MET-positive tumor. Therefore, [¹⁸F]FPC could be a potential PET imaging probe for NSCLC tumor which was sensitive to c-MET-TKIs. By virtue of this property, it will benefit NSCLC patients for c-MET-TKI treatment.