Beyond NF-κB activation: nuclear functions of IκB kinase α

IκB kinase (IKK) complex, the master kinase for NF-κB activation, contains two kinase subunits, IKKα and IKKβ. In addition to mediating NF-κB signaling by phosphorylating IκB proteins during inflammatory and immune responses, the activation of the IKK complex also responds to various stimuli to regulate diverse functions independently of NF-κB. Although these two kinases share structural and biochemical similarities, different sub-cellular localization and phosphorylation targets between IKKα and IKKβ account for their distinct physiological and pathological roles. While IKKβ is predominantly cytoplasmic, IKKα has been found to shuttle between the cytoplasm and the nucleus. The nuclear-specific roles of IKKα have brought increasing complexity to its biological function. This review highlights major advances in the studies of the nuclear functions of IKKα and the mechanisms of IKKα nuclear translocation. Understanding the nuclear activity is essential for targeting IKKα for therapeutics.     

免疫佐剂在肿瘤免疫疗法中的应用进展 *

免疫疗法是预防和治疗疾病的有效手段之一.近年来,肿瘤免疫疗法已成为一种新型治疗方法,相关肿瘤疫苗已在多种肿瘤的治疗中被证明有效.然而,在肿瘤疫苗的设计中,肿瘤抗原免疫原性弱,应答率低等问题是目前面对的一大挑战,佐剂的加入为问题的解决提供了一种新的方法和思路.免疫佐剂在提高肿瘤抗原免疫原性,激活机体适应性免疫应答等方面起着十分重要的作用.为了解近几年免疫佐剂的发展及其研究现状,针对目前常用的抗肿瘤佐剂进行综述,并总结了其对免疫系统的作用机制,为后续的疫苗设计策略提供帮助.     

中期因子在相关疾病发病机制和治疗中的研究进展

中期因子(Midkine,MK),是一种分泌型肝素结合性生长因子,具有促进细胞有丝分裂、诱导细胞恶化、促进微血管生成、抑制细胞凋亡、促进炎症介质趋化、促纤溶等功能特点;经研究发现,当机体处于健康状态时中期因子除了肾脏及小肠上皮少量表达,其他部位极少表达,但机体出现疾病时,中期因子在体内的表达明显增多,如在多种恶性肿瘤、动脉粥样硬化、各类炎症、糖尿病肾病、高血压及COPD等疾病中均监测到中期因子的高表达,进一步研究发现上述疾病的发生发展与中期因子的功能特点密切相关;近年有学者利用MK在疾病发生发展中的功能特点对疾病进行治疗,特别是MK在肿瘤领域的治疗已成为研究热点,本文结合国内外的最新研究现状就MK与相关疾病的发病机制及治疗作一简要概述,并提出进一步研究的设想。     

CD80、CD86在鼻咽癌中的表达及其临床病理意义

目的:研究CD80、CD86在鼻咽癌中的表达变化及其临床病理意义。方法:选择2014年10月至2018年10月本院接诊的鼻咽癌确诊患者64例纳入研究,依据鼻咽癌复发情况分复发组(n=30)和未复发组(n=34);同期选取正常鼻粘膜活检组织33例作为正常对照组,采用SP免疫组化法检测鼻咽癌患者癌组织或正常鼻粘膜活检组织CD80、CD86蛋白的表达,并经Spearman相关性分析法分析CD80、CD86蛋白表达与鼻咽癌恶化程度的相关性。结果:鼻咽癌的癌组织CD80、CD86蛋白均呈高表达,阳性表达主要定位于细胞膜、细胞质,与肿瘤临床TNM分期、淋巴结转移均显著相关(P0.05)。复发组、未复发组肿瘤组织中的mRNA(ARD1、Ptch1、Survivin)表达显著高于对照组,且复发组高于未复发组,差异有统计学意义(P0.05)。Spearman相关性分析显示CD80、CD86蛋白表达与鼻咽癌细胞侵袭能力呈显著正相关(r=0.403、0.547,P0.05)。结论:鼻咽癌的癌组织内CD80、CD86蛋白均呈高表达,与鼻咽癌的临床分期、淋巴结转移及放疗预后关系密切,可能作鼻咽癌临床诊治及预后评估的重要参考指标。     

中老年健康体检人群多项肿瘤标志物筛查结果及与年龄和性别的关系分析

摘要 目的：研究中老年健康体检人群多项肿瘤标志物（TM）筛查结果,分析其与年龄和性别的关系。方法：将自2017年6月至2019年12月于我院接受健康体检的600例中老年体检者纳入研究,分别以流式荧光发光法检测甲胎蛋白（AFP）、癌胚抗原（CEA）、糖类抗原-153（CA-153）、糖类抗原-125（CA-125）水平,并分析不同性别、年龄的体检者上述TM阳性率情况,分析各项TM阳性率检出疾病情况。结果：600例体检者AFP、CEA、CA-153、CA-125水平分别为（17.48±3.84）ng/mL、（4.54±1.19）ng/mL、（29.23±7.10）U/mL、（30.65±6.39）U/mL,阳性率分别为1.67%、4.00%、3.33%、3.83%。男性体检者CEA及CA-153阳性率均高于女性,而CA-125阳性率低于女性（P＜0.05）;男性与女性AFP阳性率对比不明显（P＞0.05）。81～89岁体检者的AFP、CEA、CA-153、CA-125阳性率均高于其他年龄段体检者（P＜0.05）。AFP、CEA、CA-153、CA-125阳性体检者恶性肿瘤检出率较低。结论：AFP、CEA、CA-153、CA-125表达升高,可能是中老年人群肿瘤发生、发展的早期预警,应予以高度重视,且和年龄、性别关系密切。中老年人群定期体检能够早期发现疾病并治疗,防止疾病继续恶化,保证身心健康。     

An on-lattice agent-based Monte Carlo model simulating the growth kinetics of multicellular tumor spheroids

PurposeTo develop an on-lattice agent-based model describing the growth of multicellular tumor spheroids using simple Monte Carlo tools.MethodsCells are situated on the vertices of a cubic grid. Different cell states (proliferative, hypoxic or dead) and cell evolution rules, driven by 10 parameters, and the effects of the culture medium are included. About twenty spheroids of MCF-7 human breast cancer were cultivated and the experimental data were used for tuning the model parameters.ResultsSimulated spheroids showed adequate sizes of the necrotic nuclei and of the hypoxic and proliferative cell phases as a function of the growth time, mimicking the overall characteristics of the experimental spheroids. The relation between the radii of the necrotic nucleus and the whole spheroid obtained in the simulations was similar to the experimental one and the number of cells, as a function of the spheroid volume, was well reproduced. The statistical variability of the Monte Carlo model described the whole volume range observed for the experimental spheroids. Assuming that the model parameters vary within Gaussian distributions it was obtained a sample of spheroids that reproduced much better the experimental findings.ConclusionsThe model developed allows describing the growth of in vitro multicellular spheroids and the experimental variability can be well reproduced. Its flexibility permits to vary both the agents involved and the rules that govern the spheroid growth. More general situations, such as, e. g., tumor vascularization, radiotherapy effects on solid tumors, or the validity of the tumor growth mathematical models can be studied.     

Discovery of a novel selective water-soluble SMAD3 inhibitor as an antitumor agent

Targeting the SMAD3 protein is an attractive therapeutic strategy for treating cancer, as it avoids the potential toxicities due to targeting the TGF-β signaling pathway upstream. Compound SIS3 was the first selective SMAD3 inhibitor developed that had acceptable activity, but its poor water solubility limited its development. Here, a series of SIS3 analogs was created to investigate the structure–activity relationship for inhibiting the activation of SMAD3. On the basis of this SAR, further optimization generated a water-soluble compound, 16d, which was capable of effectively blocking SMAD3 activation in vitro and had similar NK cell-mediated anticancer effects in vivo to its parent SIS3. This study not only provided a preferable lead compound, 16d, for further drug discovery or a potential tool to study SMAD3 biology, but also proved the effectiveness of our strategy for water-solubility driven optimization.     

PDCA循环在提高肿瘤患者输液港护理依从性的应用

目的探讨PDCA循环在提高肿瘤患者输液港护理依从性的应用效果。方法选取2018年2~8月我院收治的504例输液港置管的肿瘤患者按随机分配原则分为对照组240例和观察组264例,对照组给予一般治疗和常规管理,观察组在对照组基础上实施PDCA循环管理,观察两组患者的并发症发生情况、输液港护理依从性,并进行统计分析。结果观察组的并发症发生率明显低于对照组,差异有统计学意义(P<0.05);观察组的输液港护理依从性明显高于对照组,差异有统计学意义(P<0.05)。结论运用PDCA循环能优化维护流程,降低并发症,提高患者输液港护理依从性,值得临床应用。     

消癌平注射液联合表柔比星新辅助化疗对三阴性乳腺癌患者免疫功能、生活质量及血清肿瘤标志物的影响

摘要 目的：探讨消癌平注射液联合表柔比星新辅助化疗对三阴性乳腺癌（TNBC）患者免疫功能、生活质量及血清肿瘤标志物的影响。方法：选取TNBC患者89例,按照随机数字表法分为对照组和研究组,对照组（n=44）患者给予表柔比星新辅助化疗治疗,研究组（n=45）患者给予消癌平注射液联合表柔比星新辅助化疗。对比两组疗效、免疫功能、生活质量、血清肿瘤标志物及不良反应。结果：研究组治疗12周后的临床总有效率为91.11%（41/45）,高于对照组的63.64%（28/44）（P<0.05）。两组治疗12周后健康调查简表（SF-36）量表各维度评分升高,且研究组较对照组高（P<0.05）。两组治疗12周后CD4+CD25+Treg、Th17/ Treg均降低,且研究组较对照组低（P<0.05）,Th17升高,且研究组较对照组高（P<0.05）。两组治疗12周后癌胚抗原（CEA）、糖类抗原199（CA199）、糖类抗原125（CA125）均降低,且研究组较对照组低（P<0.05）。两组不良反应发生率对比未见差异（P>0.05）。结论：消癌平注射液联合表柔比星新辅助化疗治疗TNBC,具有确切的治疗效果,可降低血清肿瘤标志物水平,改善患者免疫功能和生活质量。     

肺癌住院患者营养不良风险调查及其影响因素分析

摘要 目的：肺癌住院患者营养不良风险调查及其影响因素分析。方法：选择2015年2月至2020年1月期间我院诊治的125例肺癌住院患者的临床资料进行回顾性分析。根据患者的营养状态评估结果将其分为81例营养不良组和44例营养良好组。比较两组患者的人口学资料和临床资料,采用多因素Logistic回归分析营养不良发生的影响因素。结果：营养不良患者占比64.80%（81/125）。与营养良好组相比,营养不良组年收入≥50000元患者比例明显下降（P<0.05）,营养不良组体质量指数（BMI）≤22 kg/m²患者比例、肿瘤分期III~Ⅳ期+广泛期患者比例以及肿瘤低分化患者比例明显升高,血清白蛋白水平和淋巴细胞绝对值（LYM）明显下降（P<0.05）。经多因素Logistic回归分析显示肿瘤分期III~Ⅳ期+广泛期以及肿瘤低分化是肺癌住院患者营养不良的危险因素（OR=1.743、1.812,P<0.05）,年收入≥50000元、BMI>22kg/m²、白蛋白水平≥29.55 g/L和LYM≥2.47×10⁹/L是肺癌住院患者营养不良的保护因素（OR=0.487、0.502、0.453、0.731,P<0.05）。结论：肺癌住院患者营养不良风险较高,年收入情况、BMI、肿瘤分期、分化程度、白蛋白水平以及LYM均是肺癌住院患者营养不良风险的影响因素,对上述指标进行监测有利于提前预测营养不良的发生,从而为预防肺癌住院患者营养不良的发生提供指导。