免疫细胞过继转移治疗体系的建立及其在进展期胃癌围手术期的应用

近年来,对于胃肠道肿瘤的免疫治疗发展迅速．目前临床已经将其作为一种辅助疗法与手术、化疗、放疗联合应用,以提高肿瘤综合治疗的效果。免疫细胞过继转移治疗是对于进展期胃癌免疫治疗的一个重要方法．本文综述了其在进展期胃癌围手术期的应用．并结合自身经验及临床实验观察结果．提出对于进展期胃癌综合治疗的绿色治疗新模式。     

DC-CIK过继细胞免疫治疗原发性肝癌的研究进展

【摘要】〓原发性肝癌(以下简称肝癌)临床往往较难早期发现,确诊时往往病情已进入中、晚期,病死率高。目前肝癌的治疗主要是以手术切除、肝移植、局部消融、化学治疗栓塞及其他局部区域治疗、分子靶向治疗等,但这些方法的治疗效果并不理想,患者5年存活率仍然较低。目前细胞免疫治疗现在得到了越来越多的重视,采用树突状细胞(DC)联合细胞因子诱导的杀伤细胞(cytokine induced killer, CIK)的细胞免疫治疗是其中方法之一。DC和CIK细胞是恶性肿瘤免疫治疗的两个重要因素,两者之间的相互作用及所诱发的免疫应答是免疫治疗的重要部分。现就DC-CIK过继细胞治疗原发性肝癌的研究进展予以综述。     

体外诱导骨肉瘤特异性细胞毒T淋巴细胞的实验研究

研究诱导骨肉瘤特异性细胞毒Ｔ淋巴细胞,及其体内外的抗肿瘤作用。方法：通过生化方法提取纯化骨肉瘤相关抗原,并与低剂量ＩＬ２、ＣＤ３ＭｃＡｂ协同刺激骨肉瘤致敏的淋巴细胞诱导产生ＯＳＳ－ＣＴＬ。结果：ＯＳＳ－ＣＴＬ表型特征为以ＣＤ３＋ＣＤ８＋ＣＴＬ为主的异质细胞群;对ＯＳＡＡ相关的肉瘤细胞显示高亲和杀伤活性。     

以树突状细胞为基础个体化抗胃癌过继免疫治疗的研究

目的探讨负载自体肿瘤细胞裂解物的成熟树突状细胞(ATLs-mDCs)体外诱导个体化抗胃癌过继免疫治疗的效应。方法建立短期培养的原代胃癌细胞系。用ATLs-mDCs激活自体T细胞,制备肿瘤特异性细胞毒性T细胞(CTLs)。自体树突状细胞(DCs)均分为未成熟DCs、成熟DCs和ATLs-mDCs 3组,分别应用流式细胞仪及混合淋巴细胞增殖反应方法,检测DCs的免疫功能状态;应用细胞毒杀伤试验验证肿瘤特异性CTLs的杀伤活性;应用酶联免疫吸附试验(ELISA)测定DCs培养上清中白细胞介素12(IL-12)和CTLs上清中γ干扰素(IFN-γ)的分泌水平。结果ATLs-mDCs上调HLA-DR、CD80、CD83和CD86的表达水平,同时获得高效刺激自体T细胞增殖的能力。ATLs-mDCs诱导产生的CTLs对自体胃癌细胞的杀伤率为(84±11)%,显著高于对两株异体胃癌细胞的杀伤率[(19±7)%和(19±11)%(t=54.18和56.46,P值均<0.01)]。ATLs-mDCs上清液中IL-12的浓度显著高于单纯成熟DCs(t=15.47,P<0.01)及未成熟DCs(t=28.44,P<0.01)。3组DCs分别激活自体T细胞产生的CTLs上清液中INF-γ的浓度ATLs-mDCs组高于单纯成熟DCs组(t=4.84,P<0.05),并显著高于未成熟DCs组(t=13.74,P<0.01)。结论ATLs-mDCs在体外诱导产生的CTLs能有效特异性杀伤自体胃癌细胞。     

CD3AK细胞过继治疗对肝癌患者T淋巴细胞亚群及功能活性的影响

目的　探讨CD3AK细胞过继治疗对原发性肝癌 (PLC)患者T淋巴细胞亚群及功能活性的影响。方法　5 8例PLC患者分为CD3AK细胞治疗组 (n =3 7)及对照组 (n =2 1) ,另取同期 11例献血员为正常对照组。治疗组术后第 1天开始输注CD3AK细胞 ,每天 1次 ,每次输注 2× 10 9个细胞 ,输注前 3 0min静脉注射IL 2 10 0u ,连续 5天为一疗程 ;对照组只给予与治疗组相同的保肝治疗。观察两组T淋巴细胞亚群、IL 2R、细胞增殖功能、NK及LAK活性。结果　治疗组CD4/CD8比值、NK活性、LAK活性及IL 2R表达水平和细胞增殖活力与治疗前和对照组比较 ,差异均有显著性意义。结论　过继输注CD3AK细胞治疗能够补充肝癌患者有效抗肿瘤活性细胞数量的不足 ,并能够使T淋巴细胞亚群比例失调和功能低下的状况获得不同程度的改善     

体外诱导骨肉瘤特异性细胞毒T淋巴细胞 的实验研究△

目的研究诱导骨肉瘤特异性细胞毒T淋巴细胞(OSS-CTL),及其体内外的抗肿瘤作用。方法通过生化方法提取纯化骨肉瘤相关抗原(OSAA),并与低剂量IL     

骨肉瘤细胞PCNA测定的临床意义

使用单克隆抗体测定４２例骨肉瘤化疗前后石蜡包埋切片的增殖细胞核抗原（ＰＣＮＡ），发现免疫反应阳性颗粒集中在细胞核仁区。ＰＣＮＡ标记指数分布为２１．１％～６８．５％（平均４２％），以均数４２％分为高ＰＣＮＡ指数组（ＬＩ≥４２％；ｎ＝２５）和低ＰＣＮＡ指数组（ＬＩ＜４２％；ｎ＝１７），发现高指数组肿瘤直径大于低指数组，而患者年龄、性别、肿瘤部位、组织类型及肺转移，两组统计无差异，但３年生存率，高指数组明显低于低指数组。化疗前后ＰＣＮＡ指数以增殖细胞坏死率表达可以评价化疗敏感性     

基于肿瘤新抗原的晚期肝细胞癌过继免疫细胞治疗相关进展

晚期肝细胞癌恶性程度高, 预后差, 研究发现肝癌进展与肿瘤微环境中的免疫状态存在密切关系。过继免疫细胞治疗可通过给患者输注激活的特异性免疫细胞产生抗肿瘤作用, 改善免疫抑制状态, 是肿瘤治疗的研究热点, 并在多种恶性肿瘤的治疗中展示出较好的效果, 表现出了巨大的应用潜力。在肝细胞癌治疗方面基于肿瘤新抗原的过继免疫细胞治疗成为新的热点, 而其应用方式、安全性与有效性评估、疗效预测及评价成为亟待解决的问题。本文旨在通过介绍晚期肝细胞癌过继免疫细胞治疗相关进展, 并阐述未来需要解决的问题。     

过继免疫细胞治疗预防肝癌肝移植术后复发的新思路探究

<正>我国是肝病大国,也是全球原发性肝癌(肝癌)的第一大国。我省更是肝炎、终末期肝病、肝癌的重灾区,广东地区肝脏疾病发病率高达近20%,严重危害着民众的健康。肝细胞癌(hepatocellular carcinoma,HCC)是我国最常见的恶性肿瘤之一,其死亡率居恶性肿瘤死亡率的第2位,每年大约有11万人死于HCC,占全世界HCC死亡人数的45%[1-2]。2011年中国肝移植注册网     

The current status of surgical therapy for renal artery disease

The first reports of surgically curable hypertension in the late 1930s led to enthusiasm among clinicians for removing kidneys with arterial stenosis in hypertensive patients. The development of vascular surgical techniques in the 1950s made it possible to achieve successful renal revascularization in many of these cases. However, the cause and effect relationship between a stenotic renal artery lesion and hypertension was poorly understood and many patients treated surgically had no improvement of blood pressure postoperatively. Continued experience in this field during the past two decades has significantly improved our understanding of the natural history and functional significance of renovascular disorders. Patients with renovascular hypertension can now be identified with a high degree of accuracy and successful renal revascularization is possible in most cases. Nevertheless, multiple factors must be weighed in determining whether medical or surgical therapy is more appropriate for a given patient. These include the causal relationship of renovascular disease to hypertension, the adequacy of blood pressure control with medical therapy, the natural history of untreated renovascular disease with particular regard for the risk of sustaining impaired renal function, the medical condition of the patient, the morbidity and results of surgical therapy, and the availability of other therapeutic options such as percutaneous transluminal dilatation.     

The current status of therapy for symptomatic late-onset hypogonadism with transdermal testosterone gel

For over 50 years, testosterone therapy has been used for the treatment of hypogonadism. In recent years, there has been an increase in the use of testosterone therapy for men with late-onset hypogonadism, as more convenient and effective modes of application are developed. Testosterone therapy in these men can significantly improve their sense of well-being, and lead to increases in muscle and bone mass, upper body strength, virility and libido [Gruenewald, Matsumoto. J Am Geriatr Soc 2003;51:101; Morales. Aging Male 2004; in press]. However, ensuring that optimal testosterone therapy is achieved in men with hypogonadism remains challenging. Oral delivery of unmodified testosterone is not possible, due to rapid first-pass metabolism and its short half-life. Therefore, different derivatives and formulations of testosterone have been developed to enhance potency, prolong duration of action or improve bioavailability. In addition, several different routes of administration have now been evaluated, including intramuscular injections, oral formulations, transdermal patches, transbuccal systems and transdermal testosterone gel. Despite the broad range of testosterone therapy on offer, each form has its benefits and limitations, and some will suit one patient more than another. An important concern among clinicians is that testosterone therapy may cause or promote prostate cancer. While current evidence supports the safety of testosterone therapy, androgens are growth factors for pre-existing prostate cancer. Therefore, before therapy is initiated, careful digital rectal examination and determination of prostate-specific antigen (PSA) in serum should be performed, in order to exclude evident or suspected prostate cancer. The first 3-6 months after initiating testosterone therapy is the most critical time for monitoring effects on the prostate. Therefore, it is important to monitor PSA levels every 3 months for the first year of treatment; thereafter, regular monitoring (mostly for prostate safety but also for cardiovascular and haematological safety) during therapy is mandatory.     

The current status of stem cell therapy in ischemic heart disease

The last decade has witnessed the publication of a number of stem cell clinical trials, primarily using bone marrow‐derived cells as the injected cell. Much has been learned through these “first‐generation” clinical trials. The advances in our understanding include (1) cell therapy is safe; (2) cell therapy has been mildly effective; and (3) human bone marrow‐derived stem cells do not transdifferentiate into cardiomyocytes or new blood vessels. The primary mechanism of action for cell therapy is now believed to be through paracrine effects that include the release of cytokines; chemokines; and growth factors that inhibit apoptosis and fibrosis, enhance contractility, and activate regenerative mechanisms through endogenous circulating or site‐specific stem cells. The current direction for clinical trials includes the use of stem cells capable of cardiac lineage.     

The current status of surgical pilonidal sinus disease therapy in Germany

European Surgery - Treatment of pilonidal sinus disease (PSD) requires a&nbsp;tailored approach. A&nbsp;national guideline was published in 2014. The current status of surgical PSD therapy...     

Oesophageal cancer: current status of multimodality therapy

Multimodality treatment options have been widely promoted in the therapy for locally advanced oesophageal cancer (cT3/4Nx). Generally neoadjuvant chemotherapy and combined radiochemotherapy are frequently used in this setting. The recent meta-analyses evaluating randomised trials of different neoadjuvant therapy protocols prior to surgery for patients with locally advanced oesophageal cancer showed only a modest improvement in survivial of 5-10% survival at 5 years. In contrast, the meta-analyses reveal that patients with excellent histopathological responses seem to highly benefit from neoadjuvant regimens. Patients with poor histopathological responses have no benefit but rather disadvantegeous prognoses. Therefore, predictive markers to allow individualisation of multimodality treatment in locally advanced esophageal cancer are urgently needed.