淋巴管生成与肿瘤淋巴道转移

肿瘤淋巴道转移是影响许多实体瘤预后的一个重要因素。关于肿瘤诱导的淋巴管生成的具体机制目前尚不清楚，与VEGF—C和VEGF-D的调节有关。本文综述肿瘤淋巴管生成，VEGF—C和VEGF—D基因表达，及与肿瘤淋巴道转移的关系。     

MicroRNA在肿瘤免疫中的作用：对肿瘤相关巨噬细胞的功能调控（英文）

肿瘤相关巨噬细胞(TAM)是肿瘤微环境中比例最高的免疫细胞,对肿瘤的发生和发展起着重要的作用。在肿瘤的进展过程中,microRNA可以通过转录后调控的方式作用于多种靶点与信号通路来影响TAM的表型。本文主要讨论了microRNA对巨噬细胞分化、功能性极化和细胞间信息交流的调控作用。首先,microRNA参与了从髓样细胞向成熟巨噬细胞的分化过程,这一过程直接影响了肿瘤微环境中肿瘤细胞对巨噬细胞的招募。其次,microRNA参与了TAM的功能极化,使之表现为促癌或抑癌表型,影响了肿瘤的生长和转移。第三,肿瘤细胞与巨噬细胞间的相互作用对肿瘤微环境的形成和肿瘤的进展而言是必要的,microRNA可以通过胞外颗粒的形式作为交流的媒介。此外,本文还讨论了巨噬细胞相关microRNA作为肿瘤诊断和预后标志物的潜在价值,以及基于巨噬细胞相关microRNA的肿瘤治疗新策略的应用前景。     

肿瘤细胞免疫治疗相关伦理学探讨（英文）

本文旨在对细胞免疫治疗相关的伦理学问题进行探讨,并通过分析我国细胞免疫治疗相关伦理学实践及现状,为规范我国肿瘤细胞免疫治疗的伦理标准提供参考。随着免疫学、分子生物学等学科的飞速发展和高通量测序等技术的普及,肿瘤免疫治疗已成为第四大肿瘤治疗方法。肿瘤细胞免疫治疗,如各种基于T细胞、自然杀伤(NK)细胞和树突状细胞(DC)的免疫治疗在其中发挥了重要作用。随着临床实践的开展,一些相关的伦理学问题逐渐暴露出来。如何在治疗过程中坚持基本伦理原则,有效指导并解决相关临床问题,提高治疗效果,保护受试者权益,是目前亟需研究的重要课题。本文对与之相关的伦理学问题进行探讨,并通过分析我国细胞免疫治疗相关伦理学实践及现状,以期为规范我国肿瘤细胞免疫治疗的伦理标准提供参考。     

自然杀伤细胞的生物学特性和肿瘤免疫治疗研究概述

肿瘤的发生、发展与机体免疫功能的失调密切相关,肿瘤免疫治疗因其卓越的疗效已逐渐成为继手术、放疗和化疗后的第四类肿瘤治疗方法.自然杀伤(NK)细胞是一群大颗粒淋巴细胞,在抗肿瘤免疫中发挥重要作用,其功能受到其表面的活化或抑制性蛋白样受体特异性调节.本文概述了NK细胞的生物学特性以及在肿瘤免疫治疗领域的应用研究进展.     

肿瘤相关的三级淋巴结构的检测和量化分析（英文）

肿瘤相关的三级淋巴结构（TLS）,主要由B细胞和T细胞群体有机聚集形成于肿瘤组织范围内的异位淋巴组织。在肿瘤中,TLS的存在与免疫治疗的反应性和肿瘤预后密切相关。因其具有广阔的临床应用前景,研究者一直在积极探索。许多研究都试图破译TLS的形成机制、结构组成、诱导生成、预测标记物和临床利用。与此同时,用科学的方法定性和定量描述TLS,对其研究至关重要。在检测方面,苏木精-伊红染色法（H&E）染色、多重免疫组化、多重免疫荧光和12趋化因子基因特征是被认可的方法。然而在TLS的定量分析方面,例如TLS的绝对计数、组成TLS的细胞分析、TLS的结构特征、空间位置、密度、成熟度等,目前尚无标准方法。本研究回顾了TLS检测和定量分析的最新研究进展,提出了TLS评估的新方向,并解决了TLS在临床上的定量应用问题。     

免疫炎症反应和内皮祖细胞在肉鸡肺血管丛样病变形成中的作用（英文）

目的:肺血管丛样病变是重度肺动脉高压(PAH)病人的特征病变,病变血管周围常伴有单个核细胞浸润。肺血管丛样病变在常用实验动物上难以复制,但可在肉鸡(一种生长快速的肉用型鸡)肺脏中自发形成。内皮祖细胞(EPCs)在组织再生和血管修复过程中发挥重要作用。本研究以肉鸡为模型,探讨EPCs与肺血管丛样病变形成之间的关系。创新点:证实EPCs参与了肺血管丛样病变的形成过程,并揭示了导致EPCs功能障碍的免疫学机制。方法:采集1~4周龄肉鸡肺组织,常规石蜡切片,观察肺血管丛样病变的形成情况;采用免疫组化法检测EPCs表面标志CD133和VEGFR-2的表达以及肝细胞生长因子(HGF)的表达;分离培养晚期EPCs,建立EPCs/淋巴细胞共培养体系,并在共培养体系中添加20 ng/ml HGF,观察EPCs增殖、凋亡和体外管样结构形成的变化。结论:在不同周龄的肉鸡肺组织中均可观察到处于不同发展阶段的肺血管丛样病变(图1)。早期的丛样病变主要由EPCs(CD133~+和VEGFR-2~+细胞)构成,HGF在病变实体中高表达(图2)。淋巴细胞共培养显著促进EPCs凋亡(图5),并能阻断HGF诱导的EPCs存活和体外管样结构形成(图6)。综上所述,肺血管丛样病变的形成可能与局部免疫炎症反应诱导EPCs凋亡并下调EPCs对促血管生成因子的反应性有关。     

口服免疫治疗中的生物标志物（英文）

食物过敏（food allergy,FA）是影响大量人口的全球健康问题之一,因此非常需要有效的治疗。口服免疫治疗（oral immunotherapy,OIT）在大多数FA受试者中显示出良好的疗效和安全性。OIT期间需要可靠的生物标志物进行治疗评估和结果预测。多种免疫学指标已被用作OIT的生物标志物,例如皮肤点刺试验、嗜碱性粒细胞和肥大细胞反应性、T细胞和B细胞应答反应、过敏原特异性抗体水平和细胞因子等。其他新的指标也可作为潜在的生物标志物。本文讨论并评估了各种免疫相关指标作为OIT生物标志物的应用。     

L-Se-甲基硒代半胱氨酸、D-α-生育酚琥珀酸酯、β-胡萝卜素和L-赖氨酸联合作为辅助治疗手段可预防肿瘤转移（英文）

目的：通过手术切除和辅助疗法治疗原发性肿瘤已被广泛研究,但对于肿瘤转移的有效治疗策略和药物仍然缺乏。本研究中,我们提出了一种基于组合化合物的功能性产品用作肿瘤辅助治疗,各化合物机制明确,可抑制癌症转移、改善抗癌治疗、增强免疫力和抗氧化。该组合由四种廉价化合物组成：L-硒-甲基硒代半胱氨酸（MSC）、D-α-生育酚琥珀酸（VES）、β-胡萝卜素（β-Ca）和赖氨酸（Lys）,命名为MVBL。方法：通过体外实验研究MVBL对细胞活力、细胞周期、细胞凋亡、细胞迁移、细胞侵袭、活性氧（ROS）和紫杉醇（PTX）联合治疗的影响。在动物水平测定了MVBL在体内的抗氧化和免疫增强能力。通过小鼠肿瘤模型测定MVBL在体内对肿瘤转移的抑制。结果：MVBL对肿瘤细胞的毒性高于对正常细胞的毒性。它没有显著性地影响癌细胞的细胞周期,但增加了细胞凋亡。划痕、粘附和侵袭实验结果表明,MVBL显著抑制肿瘤细胞迁移、粘附和侵袭。MVBL使乳腺癌MDA-MB-231细胞对PTX更敏感,表明它可以作为佐剂来增强化疗药物的治疗效果。小鼠实验数据表明,MVBL可以抑制肿瘤转移,延长其生存时间,增强其抗氧化能力和免疫功能。结论...     

细胞质lncRNAs与肿瘤信号调控（英文）

恶性肿瘤疾病长期作为危害人类健康的重要隐患,目前针对重要信号调控通路的一系列靶向抑制剂在临床后期业已出现耐药现象,迫切要求人们在肿瘤生物学研究和靶向治疗方向不断寻找新的可替代性靶点。长链非编码RNAs(lnc RNAs)作为最新关注的研究热点,其在肿瘤发生和转移中的重要调节功能不断被我们及相关学者重点报道。随着RNA通量深度测序等相关研究技术的推广和发展,使人们得以饱览赏析lnc RNAs作为健康和疾病重要调节因子的宏观图谱。本综述总结了胞质lnc RNAs在调节肿瘤重要信号通路中的研究进展及其在肿瘤发生发展中的作用,为癌症的预前预后和靶向治疗提供帮助。     

透明质酸在心血管和脑病变中的作用（英文）

透明质酸是细胞外基质的重要组成成分,不仅具有结构支撑功能,而且还积极参与调节细胞的功能。透明质酸的理化学和生物学特性受其自身的分子量大小以及数十种结合蛋白的影响,从而在众多的生理和病理过程中展现出多姿多彩的生物学功能。本文以心血管和脑病变为中心,总结透明质酸在这些病变的发生和修复过程中的作用,以期服务于今后的基础研究和临床实践。     

低氧诱导因子与乳腺癌转移

概肿瘤,特别是实体瘤,其内部微环境处于一种低氧或缺氧的状态,肿瘤的这种低氧微环境将诱导活化低氧诱导因子（HIF-1）信号通路。HIF-1信号通路在乳腺癌的转移中发挥着重要的作用。乳腺癌的转移涉及肿瘤细胞的浸润、进入血管、通过血液循环迁移、到达远端毛细血管内壁、穿透血管壁进入新的器官以及在新的部位形成转移灶等步骤,过程非常复杂。本文重点围绕 HIF-1在转移各个步骤中的作用进行综述。     

Successful immunological treatment of gallbladder cancer in India Case report

Gallbladder cancer has a poor outcome because of its anatomy and location. Often, the diagnosis is made very late due to its silent course. Post-operated cases do respond to chemotherapy but the survival is counted in months and the quality of life is further hampered due to toxicity of drugs. Immunotherapy holds good promise in non-responding cancers treated by conventional chemotherapeutic agents. Among various therapies, dendritic cell therapy is growing at rapid pace due to its acceptable rationale. It has been utilized in treating successfully resected stage Ill （T2, N1, M0） gallbladder cancer in one of our patients. A 48 years old lady treated with this therapy is free of metastasis with ten doses of autologous dendritic cell vaccine constructed by utilizing resected tumor lysate antigen. She has received ten doses of therapy in 14 months of her treatment. This therapy has proven to be safe and without apparent side effects. The positive clinical response obtained supports that autologous dendritic cell-based immunotherapy is a promising therapeutic approach for refractory gallbladder cancers.     

MACC1 upregulation promotes gastric cancer tumor cell metastasis and predicts a poor prognosis

In various studies, metastasis associated with colon cancer 1 (MACC1) has been frequently reported to be abnormally highly expressed in human lung cancer, colon cancer, and hepatocellular carcinoma. Our study focuses on the association of MACC1 expression with gastric cancer (GC). During our experiment, the MACC1 expression was tested in 105 GC samples using an immunohistochemical (IHC) method. The clinical characteristics and prognosis of these patients were summarized. During analysis, MACC1 distribution in GC samples with distant metastasis was higher than that in normal samples and in tumors with no dissemination. Subsequently, a lower 5-year survival rate had a strong correlation with high MACC1 expression. As a consequence, the present results suggest that MACC1 is more frequently expressed in a poor prognosis phenotype of GC and acts as a promising prognostic prediction parameter for GC.     

Chemokines and their receptors in lung cancer progression and metastasis

Lung cancer is the leading cause of cancer-related mortality around the world. Despite advancements in diagnosis, surgical techniques, and neoadjuvant chemoradiotherapy over the last decade, the mortality rate is still high and the 5-year survival is a dismal 15%. Fortunately, early detection by low-dose computed tomography (LDCT) scans has reduced mortality by 20%; yet, overall, 5-year-survival remains low at less than 20%. Therefore, in order to ameliorate this situation, a thorough understanding of the underlying molecular mechanisms is urgently needed. Chemokines and their receptors, crucial microenvironmental factors, play important roles in lung tumor genesis, progression, and metastasis, and exploring the mechanisms of this might bring new insights into early diagnosis and precisely targeted treatment. Consequently, this review will mainly focus on recent advancements on the axes of chemokines and their receptors of lung cancer.     

VEGF在膀胱移行细胞癌中的表达及临床意义

目的：探讨血管内皮生长因子（VEGF）在膀胱移行细胞癌中的表达及临床意义。方法：采用免疫组化、ELISA方法对45例膀胱移行细胞癌组织、血浆和10例正常膀胱黏膜组织、30例正常成人血浆中VEGF进行检测分析。结果：VEGF在膀胱移行细胞癌患者中呈高表达，且随分期、分级的增高而增高；膀胱癌手术前患者血浆中VEGF的浓度高于手术后。结论：1．VEGF的表达与膀胱移行细胞癌的病理分级、临床分期及生物学行为有密切关系；2．血浆中VEGF水平可有助于预测膀胱癌患者手术疗效。     

Translationally controlled tumor protein: the mediator promoting cancer invasion and migration and its potential clinical prospects

Translationally controlled tumor protein (TCTP) is a highly conserved multifunctional protein localized in the cytoplasm and nucleus of eukaryotic cells. It is secreted through exosomes and its degradation is associated with the ubiquitin-proteasome system (UPS), heat shock protein 27 (Hsp27), and chaperone-mediated autophagy (CMA). Its structure contains three α‍-helices and eleven β‍-strands, and features a helical hairpin as its hallmark. TCTP shows a remarkable similarity to the methionine-R-sulfoxide reductase B (MsrB) and mammalian suppressor of Sec4 (Mss4/Dss4) protein families, which exerts guanine nucleotide exchange factor (GEF) activity on small guanosine triphosphatase (GTPase) proteins, suggesting that some functions of TCTP may at least depend on its GEF action. Indeed, TCTP exerts GEF activity on Ras homolog enriched in brain (Rheb) to boost the growth and proliferation of Drosophila cells. TCTP also enhances the expression of cell division control protein 42 homolog (Cdc42) to promote cancer cell invasion and migration. Moreover, TCTP regulates cytoskeleton organization by interacting with actin microfilament (MF) and microtubule (MT) proteins and inducing the epithelial-mesenchymal transition (EMT) process. In essence, TCTP promotes cancer cell movement. It is usually highly expressed in cancerous tissues and thus reduces patient survival; meanwhile, drugs can target TCTP to reduce this effect. In this review, we summarize the mechanisms of TCTP in promoting cancer invasion and migration, and describe the current inhibitory strategy to target TCTP in cancerous diseases.     

P53基因蛋白在消化道肿瘤中的表达同浸润深度与转移的相关性观察

目的探讨P53基因表达与胃癌、肠癌、食管癌的相互关系.方法采用SP免疫组化染色方法.检测了消化道癌中(胃癌22例、肠癌22例、食管癌60例)P53蛋白的表达率.结果P53蛋白在胃癌中表达率最高达63.6%,肠癌中表达率为55.0%,食管癌中的表达率为61.7%.结论P53蛋白在消化道肿瘤中普遍表达并且当癌浸润较深和有淋巴结转移者阳性率较高.     

Up-regulation interleukin-6 and interleukin-8 by activated protein C in lipopolysaccharide-treated human umbilical vein endothelial cells

Objective： To investigate the effect of activated protein C （APC） on inflammatory responses in human umbilical vein endothelial cells （HUVEC） stimulated with lipopolysaccharide （LPS）. Methods： The second passage of collagenase digested HUVEC was divided into the following groups： serum free medium control group （SFM control）, phosphate buffer solution control group （PBS control）, LPS group with final concentration of 1 μg/ml （LPS group）, APC group with final concentration of 7 μg/ml, Pre-APC group （APC pretreatment for 30 min prior to LPS challenge）, and Post-APC group （APC administration 30 min after LPS challenge）. Supernatant was harvested at 0, 4, 8, 12 and 24 h after LPS challenge. Interleukin-6 （IL-6） and Interleukin-8 （IL-8） levels were analyzed with ELISA. Cells were harvested at 24 h after LPS challenge, and total RNA was extracted. Messenger RNA levels for IL-6 and IL-8 were semi-quantitatively determined by RT-PCR. Results： Compared with control group, IL-6 and IL-8 levels steadily increased 4 to 24 h after LPS stimulation. APC treatment could increase LPS-induced IL-6 and IL-8 production. The mRNA levels of IL-6 and IL-8 exhibited a similar change. Conclusion： APC can further increase the level of IL-6 and IL-8 induced by LPS. The effect of these elevated cytokines is still under investigation.