协同刺激分子PD-L1、B7-H3与B7-H4在卵巢癌中的表达及其意义

协同刺激分子PD-L1、B7-H3与B7-H4可与T细胞及其受体结合并抑制T细胞的增殖和过度活化,在细胞免疫应答过程中起重要的调控作用,已被多项研究证明与肿瘤的免疫原性及肿瘤的发生、发展密切相关。这3种分子在正常卵巢组织中均不表达,而在卵巢癌组织中呈不同程度的高表达,它们可能在促进卵巢癌的发生、转变及病情进展过程中起重要作用,研究其作用机制对卵巢癌的早期诊断及靶向治疗有一定的意义。     

共刺激分子B7：CD28与肿瘤主动免疫治疗

Ｂ７：ＣＤ２８是激发机体抗肿瘤免疫应答的共刺激信号，由于肿瘤细胞缺乏Ｂ７分子的表达，机体抗肿瘤作用显著降低，Ｂ７转基因治疗后，可以使机体重新获得对肿瘤的主动免疫应答能力，文章最后还介绍了Ｂ７基因治疗的临床方案。     

共刺激分子B7和肿瘤免疫

共刺激分子B7在T淋巴细胞的激活过程中发挥了重要作用．是目前人们最感兴趣的共刺激分子之一。属lg超家族，主要表达活化的B淋巴细胞，其对应受体是CD28分子及CTLA-4.T细胞对肿瘤的反应需要肿瘤抗原多肽由MHCI类分子提呈给CD8^ T细胞或由MHCⅡ类分子提呈给CD4^-T细胞，B7分子可协同诱导有效的．且为MHC限制的和肿瘤特异的抗肿瘤免疫．这可为肿瘤的基因治疗提供新的途径和思路。     

活体内共刺激分子PD-1抑制T细胞的功能

B7：CD28家族成员Programmed death1（PD-1）在调控T细胞功能中发挥着重要作用，其通过与配体PD—L1、PD-L2结合向T细胞内传递抑制信号，防止T细胞过度活化。近期研究表明，PD．1与肿瘤以及慢性病毒感染进程密切相关，衰竭性CTL细胞（eytotoxic Tlymphocytes）是其研究的热点之一，PD-1的表达也作为CTL细胞衰竭的重要判定标准。     

负性共刺激分子B7-H1和B7-H4在结直肠癌中的表达及其临床意义

目的:检测结直肠癌组织中负性共刺激分子B7-H1和B7-H4的表达、T细胞亚群的浸润情况,探讨其临床意义。方法:收集苏州大学附属第四医院2003年1月至2003年12月50例结直肠癌患者的癌组织标本以及5例患者的癌旁组织标本,免疫组织化学法检测结直肠癌组织中B7-H1和B7-H4的表达以及T细胞亚群的浸润,分析B7-H1、B7-H4的表达与结直肠癌患者临床病理特征及T细胞浸润的相关性,分析B7-H1、B7-H4的表达和CD3+T、CD8+T淋巴细胞浸润程度与患者预后的相关性。结果:结直肠癌组织高表达B7-H1(44%)和B7-H4(56%),而癌旁组织不表达(P<0.01)。B7-H1在结肠癌组织中的表达较直肠癌显著升高(P<0.05);随着Duke’s分期的升高,B7-H4的表达水平也呈上升趋势(P<0.05)。结直肠癌组织中B7-H1的表达与CD3+T细胞浸润呈负相关(P<0.05),但与B7-H4的表达无关。B7-H1的表达水平与患者预后呈负相关(P<0.05),且B7-H1和B7-H4同时高表达的患者总体生存率显著降低(P<0.05)。结论:负性共刺激分子B7-H1和B7-H4在人结直肠癌组织中高表达,并与患者总体生存率相关,两者的共同检测对结直肠癌诊断和预后判断具有一定的临床价值。     

共刺激分子B7家族在骨肉瘤中的研究进展

目的 骨肉瘤是好发于青少年的常见骨肿瘤之一,其发病率占原发性骨肿瘤的36％.近年来,骨肉瘤诊治水平大幅提升,但治疗效果仍不理想.随着肿瘤免疫研究的深入,人们发现在肿瘤微环境中,肿瘤浸润性T细胞是主要的抗肿瘤效应细胞,但其表面B7家族共刺激信号若发生异常,可导致肿瘤浸润性T细胞发生抑制,协助肿瘤细胞逃避机体监视而发生免疫...     

分子影像引导肿瘤免疫治疗新进展

随着肿瘤学、免疫学、影像学研究的发展,免疫治疗已成为继肿瘤传统治疗方法（化学治疗、手术治疗及放射治疗）后的又一种重要的肿瘤治疗方法。其中细胞毒性T淋巴细胞相关抗原4（CTLA-4）和程序性死亡分子1及其配体（PD-1/PD-L1）信号通路是近年来肿瘤免疫治疗研究的热点。目前的CTLA-4和PD1/PDL1药物能够特异性作用于T细胞,增强机体活化T细胞的免疫杀伤功能,在肿瘤治疗中取得了“突破性”的效果。但是,并不是所有的患者都对肿瘤免疫治疗有疗效响应,通过核素标记免疫治疗药物分子并利用分子影像学方式进行实时、在体的检测,能够为患者筛选、疗效检测、治疗方案优化、预后评估提供新方法。本综述以目前已有的核素标记免疫治疗药物临床分子显像为基点,阐述了近年肿瘤免疫治疗领域的巨大改变,并对分子影像引导肿瘤免疫治疗发展趋势进行展望。     

基于免疫抑制性受体的血液肿瘤靶向免疫治疗研究

T细胞免疫功能缺陷导致多数血液肿瘤患者不能产生有效的抗肿瘤免疫应答,从而逃避宿主免疫系统的攻击,即肿瘤细胞免疫逃逸.近年来认为肿瘤免疫抑制最为重要的机制之一是CD8+T细胞的功能耗竭,主要为免疫细胞异常表达程序性死亡分子1(PD-1)和细胞毒性T淋巴细胞相关抗原(CTLA-4)等免疫抑制所介导,而阻断此通路可以使T细胞部分或全部恢复功能.文章介绍近年来血液肿瘤中PD-1和CTLA-4及二者在介导T细胞免疫耐受中的作用及其在靶向治疗研究中的进展,为血液肿瘤的免疫靶向治疗提供新的思路.     

B7-H3与肿瘤免疫调节功能的研究进展

在机体抗肿瘤过程中,T细胞介导的免疫反应起着重要的作用。T细胞活化增殖有赖于双重信号,即由抗原递呈细胞(APC)上MHC-抗原肽复合体与TCR特异性结合传递第一信号,而第二信号由B7-CD28家族传递信号,决定T细胞的状态是增强、抑制、弱化或者演变为无反应状态。共刺激分子B7-CD28家族对决定T细胞的免疫反应起着非常     

Expression of the co-signaling molecules CD40-CD40L and their growth inhibitory effect on pancreatic cancer in vitro

We investigated the expression of the co-signalling molecule CD40 in pancreatic cancer and the growth inhibitory effect of the recombinant soluble human CD40 ligand (rshCD40L) in pancreatic cancer cell lines. Twenty-six cases of pancreatic cancer tissues and corresponding paratumoral normal tissues were immunohistochemically analyzed for CD40 expression. The association of CD40 expression with clinicopathological parameters, including clinical stage, pathological grade, invasion and metastasis, were statistically analyzed. The serum sCD40 levels in pancreatic cancer patients were examined by ELISA. The expression of CD40 in the pancreatic cancer cell lines Panc-1, Aspc-1 and Miapaca-2 was examined by RT-PCR and flow cytometry. The growth inhibitory activity of rshCD40L on pancreatic cancer cell lines was determined by MTT assay. Tumor cell apoptosis was detected by TUNEL and Annexin V/PI double staining method. CD40 was positive both on the membrane and in the cytoplasm of tumor cells, 69.2% (18/26) of the cases were positive for CD40. CD40 expression was significantly higher in pancreatic cancer tissues compared to adjacent normal tissues (P<0.05). High CD40 expression was associated with TNM stage and lymph node metastasis (both P<0.05). Patients with pancreatic cancer have higher serum sCD40L levels (3.53 ± 0.70 ng/ml) compared to healthy subjects (1.81 ± 0.48 ng/ml, P<0.05). rshCD40L significantly inhibited the proliferation of the pancreatic cancer cell lines and induced apoptosis in these cell lines. The co-signaling molecule CD40 is highly expressed in pancreatic cancer tissues and cell lines and rshCD40L is a potential tool for antitumor therapies.     

Exosomes in cancer development and clinical applications

Exosomes participate in cancer progression and metastasis by transferring bioactive molecules between cancer and various cells in the local and distant microenvironments. Such intercellular cross‐talk results in changes in multiple cellular and biological functions in recipient cells. Several hallmarks of cancer have reportedly been impacted by this exosome‐mediated cell‐to‐cell communication, including modulating immune responses, reprogramming stromal cells, remodeling the architecture of the extracellular matrix, or even endowing cancer cells with characteristics of drug resistance. Selectively, loading specific oncogenic molecules into exosomes highlights exosomes as potential diagnostic biomarkers as well as therapeutic targets. In addition, exosome‐based drug delivery strategies in preclinical and clinical trials have been shown to dramatically decrease cancer development. In the present review, we summarize the significant aspects of exosomes in cancer development that can provide novel strategies for potential clinical applications.     

外泌体在卵巢癌诊疗中的研究进展

卵巢癌是妇科常见的恶性肿瘤,具有发病率高、5年生存率低、早期不易发现、易转移反复等特点,严重威胁妇女健康.外泌体是多囊泡体与细胞膜融合后释放到细胞外直径为30~100 nm的囊泡样小体,其在肿瘤发生发展、早期诊断、化疗药物选择及治疗中的潜在价值引起了广泛关注,本文主要对外泌体在卵巢癌诊疗中的研究进展做以综述.     

Thrombolytic therapy: clinical applications

The therapeutic use of thrombolytic agents is the result of the increasing understanding of the pathophysiologic mechanisms underlying normal and deranged thrombosis and fibrinolysis. Plasminogen activators capable of increasing the production of plasmin exhibit considerable efficacy in the treatment of a variety of arterial and venous thrombotic disorders. The ideal thrombolytic agent has not been developed, but the desired clinical result of rapid opening of the thrombosed vessel without reocclusion, without activation of systemic fibrinogenolysis, and without a risk of hemorrhage are defined. Clinical studies clearly demonstrate that the addition of a variety of adjunctive agents to available thrombolytics enhances benefit without inordinate risk. The addition of intravascular angioplasty and stenting to thrombolysis increases the potential long-term benefit. Newer thrombolytic agents and new protocols for the use of existing therapies offer the promise of saving many who would otherwise succumb to coronary or cerebral arterial thrombosis or to venous thromboembolism.     

Butyric monosaccharide ester-induced cell differentiation and anti-tumor activity in mice. Importance of their prolonged biological effect for clinical applications in cancer therapy

The interest of butyric salts is based on their capacity to promote differentiation of malignant cells and inhibition of tumor development. The phenotypic modifications are rapidly reversible and require the continuous presence of butyric salts in the target area, which raises problems for therapeutic applications. We show here that the covalent binding of n-butyric acid on natural polyhydroxylated compounds such as monosaccharides, especially 3- or 6-O-butanoyl-1,2-O-isopropylidene-alpha-D-glucofuranose, retains the majority of the biological properties of n-butyric acid. The delayed degradation of these covalent compounds is associated with an improved maintenance of cell differentiation and anti-tumor protection in mice. These butyric complexes thus seem potentially useful for therapeutic applications.     

DNA origami applications in cancer therapy

Due to the complexity and heterogeneity of cancer, the development of cancer diagnosis and therapy is still progressing, and a complete understanding of cancer biology remains elusive. Recently, cancer nanomedicine has gained much interest as a promising diagnostic and therapeutic strategy, as a wide range of nanomaterials possess unique physical properties that can render drug delivery systems safer and more effective. Also, targeted drug delivery and precision medicine have now become a new paradigm in cancer therapy. With nanocarriers, chemotherapeutic drugs could be directly delivered into target cancer cells, resulting in enhanced efficiency with fewer side‐effects. DNA, a biomolecule with molecular self‐assembly properties, has emerged as a versatile nanomaterial to construct multifunctional platforms; DNA nanostructures can be modified with functional groups to improve their utilities as biosensors or drug carriers. Such applications have become possible with the advent of the scaffolded DNA origami method. This breakthrough technique in structural DNA nanotechnology provides an easier and faster way to construct DNA nanostructures with various shapes. Several experiments proved that DNA origami nanostructures possess abilities to enhance efficacies of chemotherapy, reduce adverse side‐effects, and even circumvent drug resistance. Here, we highlight the principles of the DNA origami technique and its applications in cancer therapeutics and discuss current challenges and opportunities to improve cancer detection and targeted drug delivery.     

量子点在肿瘤研究中的应用

量子点是指半径小于或接近于激子玻尔半径的半导体纳米晶粒。量子点发射荧光的可调节性强,通过改变粒子半径的大小可获得从紫外到近红外范围内任意点的光谱,且Stokes位移大。其荧光强度高而稳定,单一量子点表现出的荧光亮度和持续时间是普通有机荧光染料的10～20倍。被适当外壳包裹修饰的量子点在短时间内,对细胞的生长、发育、信号转导以及迁移等生理活动无影响。随着光学标记技术和成像技术的不断发展,现有的许多传统、常规的生物医学方法在微观上直接、实时研究生物分子的相互作用以及在临床肿瘤疾病早期诊断上都存在较大的局限性。量子点的发明及其在生物医学领域的应用,尤其是将其作为特异性标记物应用于前列腺癌、乳腺癌、子宫颈癌、皮肤基底细胞癌、肝癌、黑色素瘤等肿瘤的示踪和靶向研究中具有很大的实用价值。当前的研究主要集中在通过细胞组织等有形载体显示特定的肿瘤标志物或分子相互作用．下一步的发展方向之一就是开发这种高灵敏标记技术用于血清或其他体液成分中肿瘤分子的标记与成像,提高早期诊断率。     

The new biology of cancer: future clinical applications

Our recognition that cancer evolves by clonal selection and that the basis for this selection is the growth advantage provided by the inappropriate expression or suppression of genes present in all normal cells allows us to anticipate that the pathways of this evolutionary process may be discovered. If a finite number of such pathways exist with some commonality between various tumors, there is the possibility to anticipate the mechanisms that cell clones might use for both carcinogenesis and tumor progression and to deal with evolving clones before their survival potential becomes overwhelming. As our biochemical understanding increases we may develop the capability to do the following: to identify individuals who have inherited or acquired defective cancer suppressor genes; to identify precursor lesions more exactly; to characterize the degree of progression of a newly diagnosed tumor (has the metastatic phenotype evolved?); to develop antibodies against cell membrane proteins necessary to tumor progression; to produce immune probes that carry cytotoxins or isotopes to specific cell populations; and to take advantage of cell signals to modify tumor growth. The potential for application of the New Biology to cancer medicine seems endless.     

The design and optimization of RNA trans-splicing molecules for skin cancer therapy

Targeting tumor marker genes by RNA trans-splicing is a promising means to induce tumor cell-specific death. Using a screening system we designed RNA trans-splicing molecules (RTM) specifically binding the pre-mRNA of SLCO1B3, a marker gene in epidermolysis bullosa associated squamous cell carcinoma (EB-SCC). Specific trans-splicing, results in the fusion of the endogenous target mRNA of SLCO1B3 and the coding sequence of the suicide gene, provided by the RTM. SLCO1B3-specific RTMs containing HSV-tk were analyzed regarding their trans-splicing potential in a heterologous context using a SLCO1B3 expressing minigene (SLCO1B3-MG). Expression of the chimeric SLCO1B3-tk was detected by semi-quantitative RT-PCR and Western blot analysis. Cell viability and apoptosis assays confirmed that the RTMs induced suicide gene-mediated apoptosis in SLCO1B3-MG expressing cells. The lead RTM also showed its potential to facilitate a trans-splicing reaction into the endogenous SLCO1B3 pre-mRNA in EB-SCC cells resulting in tk-mediated apoptosis. We assume that the pre-selection of RTMs by our inducible cell-death system accelerates the design of optimal RTMs capable to induce tumor specific cell death in skin cancer cells.