三维适形放疗治疗食管鳞癌的近期疗效、生存率及预后的影响因素分析

目的:观察三维适形放疗治疗食管鳞癌的近期疗效、生存率并分析其预后的影响因素。方法:纳入我院从2010年11月～2016年10月收治的食管鳞癌患者150例进行研究,按治疗方式的不同分成研究组(n=84,三维适形放疗治疗)和常规组(n=66,常规放疗治疗)。随访3年,比较两组近期疗效、毒副反应发生情况以及3年生存情况。单因素分析研究组患者3年生存情况与性别、年龄、病变长度、病变部位、大体肿瘤体积(GTV)的关系,多因素Logistic回归分析三维适形放疗食管鳞癌患者预后的影响因素。结果:研究组治疗总有效率显著优于常规组(P0.05)。研究组放射性食管损伤、血液毒性反应发生率均显著低于常规组(均P0.05)。研究组1、2、3年存活率均显著高于常规组(均P0.05)。单因素Logistic分析结果显示:不同年龄、病变长度、病变部位以及GTV的食管鳞癌患者三年生存率比较差异有统计学意义(均P0.05)。多因素Logistic回归分析发现年龄≥70岁、病变长度≥50 mm、病变部位为胸下段、GTV≥40 cm3均是三维适形放疗食管鳞癌患者3年内死亡的危险因素。结论:三维适形放疗治疗食管鳞癌患者的近期疗效优于常规放疗,可降低毒副反应发生率,提高生存率。年龄≥70岁、病变长度≥50 mm、病变部位为胸下段、GTV≥40 cm~3均是三维适形放疗食管鳞癌患者3年内死亡的危险因素,值得临床重点关注。     

间变大细胞淋巴瘤的临床进展

间变大细胞淋巴瘤(ALCL)是一种临床上少见的恶性淋巴瘤。形态学存在着一种标志的hall mark细胞;细胞免疫学上CD30(Ki-1)表达强阳性;标志性的染色体异常t(2;5)(p23;q35)。临床诊断时多为疾病晚期(Ⅲ~Ⅳ期),并常伴有B症状。成人患者,推荐采取放疗,同时辅以联合化疗;儿童患者病程类似Burkitt淋巴瘤,治疗方案一般使用高强度的治疗淋巴母细胞白血病或Burkitti淋巴瘤的方案。高危ALCL、复发难治ALCL可应用CD30单克隆抗体和ALK蛋白抑制剂等。临床上报道较少,对其认识仍有不足。近年来虽然对ALCL的研究取得了显著的进展,但至今尚未形成成熟规范的治疗方案。未来研究有望最终寻找到ALCL的最优化治疗方案。现就其在免疫和遗传学、形态学、临床表现、治疗和预后等方面的研究进展作一综述。     

Rationally optimized cryopreservation of multiple mouse embryonic stem cell lines: I—Comparative fundamental cryobiology of multiple mouse embryonic stem cell lines and the implications for embryonic stem cell cryopreservation protocols

The post-thaw recovery of mouse embryonic stem cells (mESCs) is often assumed to be adequate with current methods. However as this publication will show, this recovery of viable cells actually varies significantly by genetic background. Therefore there is a need to improve the efficiency and reduce the variability of current mESC cryopreservation methods. To address this need, we employed the principles of fundamental cryobiology to improve the cryopreservation protocol of four mESC lines from different genetic backgrounds (BALB/c, CBA, FVB, and 129R1 mESCs) through a comparative study characterizing the membrane permeability characteristics and membrane integrity osmotic tolerance limits of each cell line. In the companion paper, these values were used to predict optimal cryoprotectants, cooling rates, warming rates, and plunge temperatures, and then these predicted optimal protocols were validated against standard freezing protocols.     

T cell activation induces CuZn superoxide dismutase (SOD)-1 intracellular re-localization,production and secretion

Reactive oxygen species (ROS) behave as second messengers in signal transduction for a series of receptor/ligand interactions. A major regulatory role is played by hydrogen peroxide (H₂O₂), more stable and able to freely diffuse through cell membranes. Copper–zinc superoxide dismutase (CuZn-SOD)-1 is a cytosolic enzyme involved in scavenging oxygen radicals to H₂O₂ and molecular oxygen, thus representing a major cytosolic source of peroxides. Previous studies suggested that superoxide anion and H₂O₂ generation are involved in T cell receptor (TCR)-dependent signaling. Here, we describe that antigen-dependent activation of human T lymphocytes significantly increased extracellular SOD-1 levels in lymphocyte cultures. This effect was accompanied by the synthesis of SOD-1-specific mRNA and by the induction of microvesicle SOD-1 secretion. It is of note that SOD-1 increased its concentration specifically in T cell population, while no significant changes were observed in the “non-T” cell counterpart. Moreover, confocal microscopy showed that antigen-dependent activation was able to modify SOD-1 intracellular localization in T cells. Indeed, was observed a clear SOD-1 recruitment by TCR clusters. The ROS scavenger N-acetylcysteine (NAC) inhibited this phenomenon. Further studies are needed to define whether SOD-1-dependent superoxide/peroxide balance is relevant for regulation of T cell activation, as well as in the functional cross talk between immune effectors.     

B-Myb稳定过表达H1299细胞株的构建与分析

B—Myb是Myb家族的成员之一,在细胞周期和癌变过程中具有重要作用。但其在肺癌中的作用及其分子机制仍不清楚。为了研究B—Myb在肺癌中的作用,构建了B-Myb稳定过表达的H1299肺癌细胞株。流式细胞术和MTT检测的结果表明,B—Myb稳定过表达导致G1期细胞减少,S期细胞增加进而促进细胞增殖：克隆形成实验及Transwell的结果表明,B—Myb稳定过表达显著增强H1299细胞的克隆形成、侵袭及迁移能力。定量RT-PCR检测结果表明,B—Myb稳定过表达显著提高了细胞周期基因CCNA1的表达水平;对CD97和MTSS1等细胞运动相关下游基因的表达则无明显影响。该研究成功构建了B-Myb稳定过表达细胞株,发现了B-Myb过表达可促进肺癌细胞的增殖、侵袭迁移及克隆形成能力,为进一步研究奠定了基础。     

Using the BLT Humanized Mouse as a Stem Cell based Gene Therapy Tumor Model

Small animal models such as mice have been extensively used to study human disease and to develop new therapeutic interventions. Despite the wealth of information gained from these studies, the unique characteristics of mouse immunity as well as the species specificity of viral diseases such as human immunodeficiency virus (HIV) infection led to the development of humanized mouse models. The earlier models involved the use of C. B 17 scid/scid mice and the transplantation of human fetal thymus and fetal liver termed thy/liv (SCID-hu) ^{1, 2} or the adoptive transfer of human peripheral blood leukocytes (SCID-huPBL) ³. Both models were mainly utilized for the study of HIV infection.One of the main limitations of both of these models was the lack of stable reconstitution of human immune cells in the periphery to make them a more physiologically relevant model to study HIV disease. To this end, the BLT humanized mouse model was developed. BLT stands for bone marrow/liver/thymus. In this model, 6 to 8 week old NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) immunocompromised mice receive the thy/liv implant as in the SCID-hu mouse model only to be followed by a second human hematopoietic stem cell transplant ⁴. The advantage of this system is the full reconstitution of the human immune system in the periphery. This model has been used to study HIV infection and latency ^5-8.We have generated a modified version of this model in which we use genetically modified human hematopoietic stem cells (hHSC) to construct the thy/liv implant followed by injection of transduced autologous hHSC ^{7, 9}. This approach results in the generation of genetically modified lineages. More importantly, we adapted this system to examine the potential of generating functional cytotoxic T cells (CTL) expressing a melanoma specific T cell receptor. Using this model we were able to assess the functionality of our transgenic CTL utilizing live positron emission tomography (PET) imaging to determine tumor regression (9).The goal of this protocol is to describe the process of generating these transgenic mice and assessing in vivo efficacy using live PET imaging. As a note, since we use human tissues and lentiviral vectors, our facilities conform to CDC NIH guidelines for Biosafety Level 2 (BSL2) with special precautions (BSL2+). In addition, the NSG mice are severely immunocompromised thus, their housing and maintenance must conform to the highest health standards (http://jaxmice.jax.org/research/immunology/005557-housing.html).     

Sesquiterpenoids from the Resina Commiphora Promoting the Apoptotic Activity of PC-3 Prostate Cancer Cells

Four new germacrane-type sesquiterpenes commiphoranes M1-M4 ( 1 - 4 ) together with eighteen sesquiterpenes were isolated from the Resina Commiphora. The structures and relative configurations of new substances were determined by using spectroscopic methods. Biological activity investigation revealed that nine compounds including 7 , 9 , 14 , 16 , (+)- 17 , (−)- 17 , 18 , 19 , and 20 could induce the apoptosis of prostate cancer originated PC-3 cells, through classic apoptosis signaling pathway, even using flow cytometry showed that the compound (+)- 17 caused apoptosis of PC-3 cells more than 40 %, suggesting their potential therapeutic application in the development of novel drugs against prostate cancer.     

Kidney proteome responses in the teleost fish Paralichthys olivaceus indicate a putative immune response against Streptococcus parauberis

The proteomic response to bacterial infection in a teleost fish (Paralichthys olivaceus) infected with Streptococcus parauberis was analyzed using label-free protein quantitation coupled with LC-MS(E) tandem mass spectrometry. A total of 82 proteins from whole kidney, a major lymphoid organ in this fish, were found to be differentially expressed between healthy and diseased fish analyzed 6, 24, 72 and 120 h post-infection. Among the differentially expressed proteins, those involved in mediating immune responses (e.g., heat shock proteins, cathepsins, goose-type lysozyme and complement components) were most significantly up-regulated by infection. In addition, cell division cycle 48 (CDC48) and calreticulin, which are associated with cellular recovery and glycoprotein synthesis, were up-regulated in the universal protein group, whereas the other proteins in that group were down-regulated. There was continuous activation of expression of immune-associated proteins during infection, but there was also loss of expression of proteins not involved in immune function. We expect that our findings regarding immune response at the protein level would offer new insight into the systemic response to bacterial infection of a major immune organ in teleost fish.