BACKGROUND & AIMS: Interleukin-1 alpha (IL-1 alpha) induces cell motility in a variety of benign cell types and in some but not all malignant cell lines in vitro. This study characterizes the IL-1 alpha-induced motility of an aggressive human melanoma cell line that expresses both type I and type II IL-1 receptors. We tested the effect of monoclonal antibodies including function-blocking moAbs against the type I and type II IL-1 receptors on melanoma cell motility to determine which receptor is involved in signal transduction of IL-1 alpha-induced melanoma cell motility. IL-1 alpha significantly increases MM-RU melanoma cell migration in a dose-dependent manner using modified Boyden chamber assays at concentrations 10 to 100 times less than concentrations that significantly inhibit cell growth. Computer-assisted time-lapse image analysis reveals that the motility is inhibited in a dose-dependent manner by neutralizing antibodies against IL-1 alpha. Function-blocking monoclonal antibodies against either type I or type II IL-1 receptors show a significant inhibition of cytokine-induced enhanced cell migration. When both the anti-IL-1 receptor antibodies are added together, the motility-response is completely blocked to control levels. Taken together the data indicate that the IL-1 alpha-induced motility of MM-RU melanoma cells is mediated through both type I and type II IL-1 receptors. The significant inhibition of motility by neutralizing IL-1 alpha or blocking either one or both of the IL-1 receptors indicates an integration of IL-1-induced signals in the induction of melanoma cell migration.

背景与目标： Interleukin-1 α (IL-1 α) 在体外诱导多种良性细胞类型和一些但不是全部恶性细胞系中的细胞运动。这项研究表征了表达I型和II型IL-1受体的侵袭性人类黑素瘤细胞系的IL-1 α 诱导的运动。我们测试了单克隆抗体 (包括针对I型和II型IL-1受体的功能阻断moab) 对黑色素瘤细胞运动的影响，以确定哪种受体参与IL-1 α 诱导的黑色素瘤细胞运动的信号转导。IL-1 α 以剂量依赖的方式显著增加MM-RU黑素瘤细胞迁移，使用改进的Boyden室测定法，浓度低于显著抑制细胞生长的浓度的10至100倍。计算机辅助延时图像分析表明，通过中和针对IL-1 α 的抗体，运动性以剂量依赖的方式受到抑制。针对I型或II型IL-1受体的功能阻断单克隆抗体显示出对细胞因子诱导的增强细胞迁移的显着抑制。当两种anti-IL-1受体抗体加在一起时，运动反应完全阻断到控制水平。总之，这些数据表明，IL-1 α 诱导的MM-RU黑素瘤细胞的运动是通过I型和II型IL-1受体介导的。通过中和IL-1 α 或阻断一种或两种IL-1受体而显着抑制运动，表明IL-1-induced信号在诱导黑色素瘤细胞迁移中的整合。

BACKGROUND & AIMS: :The objective of this study was to determine whether paclitaxel and a strong antioxidant, pyrrolidinedithiocarbamate (PDTC), can affect the activation of nuclear factor-kappa B (NF-kappaB) in SKOV-3 human ovarian cancer cell line and the effect of these two agents on the growth and apoptosis of the cancer cells. The cells were treated with various concentrations of paclitaxel and/or PDTC at various time intervals. Following treatments, cell growth and apoptosis were determined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphonyl)-2H-tetrazolium (WST-8) (WST) assay and flow cytometry, respectively. Western blot assay was used to determine the nuclear p65 protein and cytoplasmic IkappaB-alpha protein. High doses of PDTC significantly inhibited the growth of SKOV-3 cells and caused apoptosis. Paclitaxel and lower doses of PDTC combined demonstrated additive inhibition of cell growth and increased levels of apoptosis. Treatment of paclitaxel alone showed increased nuclear p65 protein and decreased cytoplasmic IkappaB-alpha protein expression, while pretreatment of PDTC reversed this function. PDTC blocks the paclitaxel-induced activation of NF-kappaB leading to increased chemosensitivity to paclitaxel and enhanced apoptosis. Combining antioxidants and paclitaxel has significant potential to overcome the risk of paclitaxel resistance.

背景与目标： : 这项研究的目的是确定紫杉醇和强抗氧化剂吡咯烷二硫代氨基甲酸酯 (PDTC) 是否会影响SKOV-3人卵巢癌细胞系中核因子-κ B (NF-κ B) 的活化以及这两种药物对癌细胞生长和凋亡的影响。在不同的时间间隔用各种浓度的紫杉醇和/或PDTC处理细胞。处理后，通过2-(2-甲氧基-4-硝基苯基)-3-(4-硝基苯基)-5-(2,4-二硫酰基)-2h-四唑 (WST-8) (WST) 测定和流式细胞仪测定细胞生长和凋亡。Western blot测定法用于测定核p65蛋白和细胞质IkappaB-α 蛋白。高剂量的PDTC显著抑制SKOV-3细胞的生长并引起细胞凋亡。紫杉醇和较低剂量的PDTC组合显示出对细胞生长的加性抑制和凋亡水平的增加。单独治疗紫杉醇显示核p65蛋白增加，胞质IkappaB-α 蛋白表达降低，而PDTC的预处理逆转了这一功能。PDTC阻断紫杉醇诱导的NF-κ b激活，从而增加对紫杉醇的化学敏感性并增强细胞凋亡。结合抗氧化剂和紫杉醇具有克服紫杉醇耐药性风险的巨大潜力。

BACKGROUND & AIMS: BACKGROUND:Germ cells are the only cell type that can penetrate from one generation to next generation. At the early embryonic developmental stages, germ cells originally stem from primordial germ cells, and finally differentiate into functional gametes, sperm in male or oocyte in female, after sexual maturity. This study was conducted to investigate a large-scale expressed sequence tag (EST) analysis in chicken PGCs and compare the expression of the PGC ESTs with that of embryonic gonad. RESULTS:We constructed 10,851 ESTs from a chicken cDNA library of a collection of highly separated embryonic PGCs. After chimeric and problematic sequences were filtered out using the chicken genomic sequences, there were 5,093 resulting unique sequences consisting of 156 contigs and 4,937 singlets. Pearson chi-square tests of gene ontology terms in the 2nd level between PGC and embryonic gonad set showed no significance. However, digital gene expression profiling using the Audic's test showed that there were 2 genes expressed significantly with higher number of transcripts in PGCs compared with the embryonic gonads set. On the other hand, 17 genes in embryonic gonads were up-regulated higher than those in the PGC set. CONCLUSION:Our results in this study contribute to knowledge of mining novel transcripts and genes involved in germline cell proliferation and differentiation at the early embryonic stages.

背景与目标：

BACKGROUND & AIMS: :Accumulation of lipid-laden macrophages is a hallmark of atherosclerosis. The relevance of the key transcription factor nuclear factor kappaB (NF-kappaB) for macrophage-derived foam-cell formation has not been unequivocally resolved. Transgenic mice lines were generated in which NF-kappaB activation is specifically inhibited in macrophages by overexpressing a trans-dominant, non-degradable form of IkappaBalpha (IkappaBalpha (32A/36A)) under control of the macrophage-specific SR-A promoter. Alanine substitution of serines 32 and 36 prevents degradation and retains the inactive NF-kappaB/IkappaBalpha (32A/36A) complex in the cytoplasm. Similarly, stable human THP1 monocytic cell lines were generated with integrated copies of IkappaBalpha (32A/36A) cDNA. Upon treatment with oxidized low-density lipoprotein (ox-LDL), murine peritoneal macrophages from transgenic IkappaBalpha (32A/36A) mice, as well as THP1/IkappaBalpha (32A/36A) clones, display decreased lipid loading after differentiation into macrophages. This is accompanied by increased expression of the transcription factors PPARgamma and LXRalpha as well as of the major cholesterol-efflux transporter ABCA1. Paradoxically, mRNA expression of the 'lipid-uptake' receptor CD36 is also increased. Since the net result of these changes is reduction of foam-cell formation, it is proposed that under specific inhibition of NF-kappaB activation, ABCA1-mediated cholesterol efflux prevails over CD36-mediated lipid influx.

背景与目标： : 富含脂质的巨噬细胞的积累是动脉粥样硬化的标志。关键转录因子核因子kappaB (NF-kappaB) 与巨噬细胞衍生的泡沫细胞形成的相关性尚未明确解决。产生了转基因小鼠品系，其中在巨噬细胞特异性SR-a启动子的控制下，通过过表达反式显性，不可降解形式的IkappaBalpha (32A/36A))，在巨噬细胞中特异性抑制NF-kappaB的激活。丝氨酸32和36的丙氨酸取代可防止降解，并在细胞质中保留无活性的NF-kappaB/IkappaBalpha (32A/36A) 复合物。同样，用IkappaBalpha (32A/36A) cDNA的整合拷贝生成了稳定的人THP1单核细胞系。用氧化的低密度脂蛋白 (ox-LDL) 处理后，来自转基因IkappaBalpha (32A/36A) 小鼠的鼠腹膜巨噬细胞以及THP1/IkappaBalpha (32A/36A) 克隆在分化为巨噬细胞后显示出降低的脂质负荷。这伴随着转录因子PPARgamma和LXRalpha以及主要胆固醇外排转运蛋白abca1的表达增加。矛盾的是，“脂质摄取” 受体CD36的mRNA表达也增加。由于这些变化的最终结果是减少了泡沫细胞的形成，因此提出在NF-κ b活化的特异性抑制下，ABCA1-mediated胆固醇外排优于CD36-mediated脂质内流。

BACKGROUND & AIMS: A 38-year-old man, blood group A+, was allotransplanted for multiple myeloma from his fully matched sister, blood group O+. Anti-A antibodies IgG and IgM titres of the donor were low. Allogeneic peripheral blood stem cells were harvested by leukapheresis after subcutaneous administration of G-CSF. Rapid engraftment occurred since 5.6 x 10(9)/l leukocytes were achieved on day +9 post-transplant. At this time a severe immune haemolytic syndrome occurred and direct antiglobulin test was positive (IgG and C3d). Elution showed an anti-A specificity. Evolution was rapidly unfavourable related to multiorgan failure. The patient died on day +20 post-transplant.

背景与目标： 一名38岁的A血型男子从其完全匹配的姐姐O血型中同种异体移植了多发性骨髓瘤。供体的抗A抗体IgG和IgM滴度较低。皮下给予g-csf后，通过白细胞分离术收集异基因外周血干细胞。由于在移植后第9天实现了5.6 × 10(9)/l白细胞，因此发生了快速植入。此时发生了严重的免疫溶血综合征，直接抗球蛋白试验呈阳性 (IgG和C3d)。洗脱显示出抗A特异性。进化与多器官衰竭迅速不利。患者在移植后第20天死亡。

BACKGROUND & AIMS: :We have translated RNAs for the two rat asialoglycoprotein receptor polypeptides together in a cell-free system containing dog pancreatic microsomes and immunoprecipitated the products with antibodies that distinguish the two proteins. In this system the proteins oligomerize, as judged by their coprecipitation with either of the subunit-specific antisera. Oligomerization does not occur between subunits synthesized without microsomes or between subunits synthesized on separate microsomes mixed during detergent solubilization. Thus, oligomerization occurs within the microsomal membrane. We calculate that oligomerization proceeds with an efficiency of approximately 85%. The receptor complex appears to represent a specific oligomer because it excludes a third membrane glycoprotein synthesized in the same reaction. Oligomerization of the asialoglycoprotein receptor in vitro should provide a useful system to study the assembly of a membrane-protein complex.

背景与目标： : 我们已经在包含狗胰腺微粒体的无细胞系统中将两种大鼠去唾液酸糖蛋白受体多肽的rna翻译在一起，并用区分这两种蛋白质的抗体免疫沉淀了产物。在该系统中，蛋白质寡聚，根据它们与亚基特异性抗血清中的任何一种的共沉淀来判断。在没有微粒体的情况下合成的亚基之间或在洗涤剂增溶过程中混合的单独的微粒体上合成的亚基之间不会发生低聚。因此，低聚发生在微粒体膜内。我们计算低聚化以约85% 的效率进行。受体复合物似乎代表特定的寡聚体，因为它排除了在同一反应中合成的第三种膜糖蛋白。体外去唾液酸糖蛋白受体的寡聚化应为研究膜蛋白复合物的组装提供有用的系统。

BACKGROUND & AIMS: :Etanercept is a recombinant human soluble tumor necrosis factor (TNF-alpha) receptor fusion protein that inhibits TNF-alpha, a major mediator in the pathogenesis of graft-versus-host disease (GVHD). The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in 21 patients with steroid-refractory acute GVHD (aGVHD) (n = 13) and chronic GVHD (cGVHD) (n = 8). Etanercept 25 mg was given subcutaneously twice weekly for 4 weeks followed by 25 mg weekly for 4 weeks. At the time of initiation of etanercept, 14 patients had skin, 13 had gastro-intestinal, 5 had liver, 5 had pulmonary, and 4 had oral involvement. Twelve patients (57%) completed 12 doses of therapy. Overall, 11 of 21 patients (52%) responded to the treatment with etanercept, including 6 patients (46%) with aGVHD [n = 4 complete response (CR), n = 2 partial response (PR)] and 5 patients (62%) with cGVHD (n = 1 CR, n = 4 PR). Clinical responses were most commonly seen in patients with refractory gut aGVHD with 55% of the patients having a CR and 9% having a PR. CMV reactivation occurred in 48% of patients, bacterial infections in 14% of patients, and fungal infections in 19% of patients. Fourteen patients (67%) were alive after a median follow-up of 429 days (range 71-1007 days) since initiation of etanercept. Seven patients died, 3 of infections, 2 of refractory aGVHD, and 2 of disease progression. In conclusion, our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid-refractory aGVHD and cGVHD, particularly in the setting of GI involvement.

背景与目标： : 依那西普是一种重组人可溶性肿瘤坏死因子 (TNF-α) 受体融合蛋白，可抑制TNF-α，TNF-α 是移植物抗宿主病 (GVHD) 发病机理中的主要介质。我们研究的目的是评估依那西普治疗21例类固醇难治性急性GVHD (aGVHD) (n = 13) 和慢性GVHD (cGVHD) (n = 8) 患者的安全性和有效性。依那西普25 mg，每周皮下注射两次，持续4周，然后每周注射25 mg，持续4周。在开始使用依那西普时，14例患者有皮肤，13例有胃肠道，5例有肝脏，5例有肺部，4例有口腔受累。12名患者 (57%) 完成12剂治疗。总体而言，21例患者中有11例 (52%) 对依那西普治疗有反应，其中6例 (46% 例) aGVHD [n = 4完全缓解 (CR)，n = 2部分缓解 (PR)] 和5例 (62%) cGVHD (n = 1 CR，n = 4 PR)。临床反应最常见于难治性肠道aGVHD患者，其中55% 患者具有CR，9% 患者具有PR。48% 患者发生CMV再激活，14% 患者发生细菌感染，19% 患者发生真菌感染。自依那西普开始以来，中位随访429天 (范围71-1007天) 后，有14名患者 (67%) 还活着。7例患者死亡，3例感染，2例难治性aGVHD，2例疾病进展。总之，我们的初步数据表明，依那西普具有良好的耐受性，并且可以在类固醇难治性aGVHD和cGVHD患者中诱导高反应率，尤其是在GI受累的情况下。

BACKGROUND & AIMS: :The mechanism by which T cells signal other T cells is not well defined. This was investigated by studying the ability of circulating T cells to induce the proliferation of autologous T cell clones. Peripheral blood T cells activated by cross-linking of the CD3/T cell receptor complex, which increased the expression of cell adhesion molecules LFA-1, LFA-3 and ICAM-1, induced the proliferation of autologous T cell clones. Irradiated antigen-activated peripheral blood T cells could also induce the proliferation of T cell clones which could not recognize that antigen. T-T cell activation required cell contact, was not major histocompatibility complex (MHC) restricted and was blocked by monoclonal antibodies directed against adhesion molecules CD2 and LFA-3 but was not blocked by antibody to class II MHC determinants. As CD2 is the natural ligand for LFA-3, increased expression of T cell surface adhesion molecules LFA-1, ICAM-1 and particularly LFA-3 during an inflammatory response may rapidly recruit T cells that are activated through the CD2 pathway. These results allow a simplified model to explain how relatively few antigen/MHC-specific T cells can recruit large numbers of non-antigen-specific T cells in the generation of an inflammatory response and postulates a novel role of the CD2 molecule in T cell immune function.

背景与目标： : T细胞向其他T细胞发出信号的机制尚不明确。通过研究循环T细胞诱导自体T细胞克隆增殖的能力进行了研究。通过CD3/T细胞受体复合物交联激活的外周血T细胞，增加细胞粘附分子LFA-1、LFA-3和ICAM-1的表达，诱导自体T细胞克隆增殖。辐照的抗原激活的外周血T细胞也可以诱导无法识别该抗原的T细胞克隆的增殖。T-t细胞活化需要细胞接触，不受主要组织相容性复合物 (MHC) 的限制，并被针对粘附分子CD2和LFA-3的单克隆抗体阻断，但未被针对II类MHC决定簇的抗体阻断。由于CD2是LFA-3的天然配体，因此在炎症反应期间LFA-1、ICAM-1并且特别是LFA-3的T细胞表面粘附分子的表达增加可以快速募集通过CD2途径激活的T细胞。这些结果允许一个简化的模型来解释相对较少的抗原/MHC特异性T细胞如何在炎症反应的产生中募集大量非抗原特异性T细胞，并假设CD2分子在T细胞免疫功能中的新作用。

BACKGROUND & AIMS: The involvement of antigen-specific T cells in the pathogenesis of collagen diseases is still controversial. The final stages of collagen diseases are usually characterized by the dominance of inflammation. Therefore, antigen non-specific factors, such as inflammatory cytokines, probably play an important role in this process. On the other hand, the methods available to analyze the antigen-specific aspects of the immune response are still limited. Here we review our novel system of T cell clonality analysis based on the idea that activated antigen-specific T cells should form accumulating clones among the lymphocyte population. Using this method, dynamic changes of clonal accumulation of T cells could be evaluated during antigenic stimulation in vivo and in vitro. The significance of antigen-specific T cell clones in collagen diseases is discussed using data obtained from patients with rheumatoid arthritis and systemic lupus erythematosus.

背景与目标： 抗原特异性T细胞参与胶原疾病的发病机理仍存在争议。胶原蛋白疾病的最后阶段通常以炎症为主。因此，抗原非特异性因子 (如炎性细胞因子) 可能在这一过程中起重要作用。另一方面，用于分析免疫应答的抗原特异性方面的方法仍然有限。在这里，我们基于激活的抗原特异性T细胞应在淋巴细胞群体中形成累积克隆的想法，回顾了我们的新型T细胞克隆分析系统。使用该方法，可以在体内和体外评估抗原刺激过程中T细胞克隆积累的动态变化。使用类风湿关节炎和系统性红斑狼疮患者获得的数据讨论了抗原特异性T细胞克隆在胶原疾病中的意义。

BACKGROUND & AIMS: Inflammatory cell infiltration of the lung is a predominant histopathological change that occurs during radiation pneumonitis. Emigration of inflammatory cells from the circulation requires the interaction between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. We studied the immunohistochemical pattern of expression of cell adhesion molecules in lungs from mice treated with thoracic irradiation. After X-irradiation, the endothelial leukocyte adhesion molecule 1 (ELAM-1; E-selectin) was primarily expressed in the pulmonary endothelium of larger vessels and minimally in the microvascular endothelium. Conversely, the intercellular adhesion molecule 1 (ICAM-1; CD54) was expressed in the pulmonary capillary endothelium and minimally in the endothelium of larger vessels. Radiation-mediated E-selectin expression was first observed at 6 h, whereas ICAM-1 expression initially increased at 24 h after irradiation. ICAM-1 and E-selectin expression persisted for several days. P-selectin is constitutively expressed in Weibel-Palade bodies in the endothelium, which moved to the vascular lumen within 30 min after irradiation. P-selectin was not detected in the pulmonary endothelium at 6 h after irradiation. The radiation dose required for increased cell adhesion molecule expression within the pulmonary vascular endothelium was 2 Gy, and expression increased in a dose-dependent manner. These data demonstrate that ICAM-1 and E-selectin expression is increased in the pulmonary endothelium following thoracic irradiation. The pattern of expression of E-selectin, P-selectin, and ICAM-1 is distinct from one another.

背景与目标： 肺炎性细胞浸润是放射性肺炎期间发生的主要组织病理学变化。炎症细胞从循环中迁移需要血管内皮上的细胞粘附分子与白细胞表面的分子之间的相互作用。我们研究了经胸部照射治疗的小鼠肺中细胞粘附分子表达的免疫组织化学模式。X射线照射后，内皮白细胞粘附分子1 (ELAM-1; E-选择素) 主要在较大血管的肺内皮中表达，而在微血管内皮中表达最少。相反，细胞间粘附分子1 (ICAM-1; CD54) 在肺毛细血管内皮中表达，而在较大血管的内皮中表达最少。首先在6小时观察到辐射介导的E-选择素表达，而ICAM-1表达最初在辐射后24小时增加。ICAM-1和E-选择素表达持续数天。P-选择素在内皮的Weibel-Palade体中组成性表达，在照射后30分钟内移至血管腔。照射后6小时，在肺内皮中未检测到P-选择素。肺血管内皮细胞粘附分子表达增加所需的辐射剂量为2 Gy，并且表达以剂量依赖性方式增加。这些数据表明，胸部照射后，肺内皮中ICAM-1和E-选择素的表达增加。E-选择素，P-选择素和ICAM-1的表达模式彼此不同。

BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to assess the potential contribution of HLA-class I MICA and HLA-B gene polymorphisms towards the pathogenesis of giant cell arteritis (GCA). METHODS:Ninety-eight biopsy-proven GCA patients and 225 ethnically matched controls from Lugo, Northwest Spain, were genotyped for the MICA-TM microsatellite polymorphism using a polymerase chain reaction (PCR)-based method. Genotyping of HLA-B was performed using PCR and detection with a reverse sequence-specific oligonucleotide (SSO) probes system. RESULTS:A significant difference in the distribution of the alleles of MICA between patient and control groups (P = 0.005) was found. This was due to an increased frequency of the MICA A5 allele in GCA patients compared with controls (26 vs 13.6%; P = 0.0001; P(C) = 0.0005; OR 2.2, 95% CI 1.4-3.4). In addition, the HLA-B*15 allele showed a higher frequency in GCA patients compared with controls (P = 0.004; P(C) = 0.04; OR 2.7, 95% CI 1.3-5.7). Interestingly, the association observed with the MICA A5 allele seems to be independent of linkage disequilibrium with HLA-B, as well as independent of that previously described with HLA-DRB1*04. Remarkably, simultaneous presence of MICA A5 and HLA-B*15 or HLA-DRB1*04 genetic markers leads to an increase in the OR obtained for each individual genetic marker (MICA A5 + B*15 OR 3.2; MICA A5 + DRB1*04 OR 5.8). CONCLUSIONS:Our results provide the first evidence that the MICA and HLA-B genes are independently associated with the genetic susceptibility to GCA, and suggest that several genes within the MHC might have independent effects in the susceptibility to this systemic vasculitis.

背景与目标：

BACKGROUND & AIMS: Death while in custody is a sensitive issue as it has the potential to cause legal ramifications and political fall-out, to embarrass the law enforcement community, and to incite the general population. Studies of deaths while in custody show that natural deaths are much more common than both suicides and homicides combined. Studies also indicate that natural deaths cluster in the older population, while suicides, on the other hand, occur predominantly in the younger population. We present a summary and discussion of a death in custody that is unique in several aspects. Contrary to the norm, death in this 18-year-old male inmate was natural. It was due to a rare complication (colopericardial fistula) of a surgical procedure (colonic interposition) performed roughly 16 years previously. We believe that our case represents the third example of a colopericardial fistula and the first to occur following corrective surgery for esophageal atresia.

背景与目标： 在押期间死亡是一个敏感问题，因为它有可能引起法律后果和政治后果，使执法部门感到尴尬，并煽动普通民众。对在押期间死亡的研究表明，自然死亡比自杀和凶杀案的总和要普遍得多。研究还表明，自然死亡聚集在老年人口中，而自杀则主要发生在年轻人口中。我们对羁押中的死亡进行了总结和讨论，这在几个方面都是独一无二的。与正常情况相反，这名18岁的男性囚犯的死亡是自然的。这是由于大约16年前进行的外科手术 (结肠介入) 的罕见并发症 (心包瘘) 所致。我们认为，我们的病例代表了心包瘘的第三个例子，并且是在食管闭锁的矫正手术后首次发生的例子。

BACKGROUND & AIMS: CD4+ anti-tumor T cells reactive with rat adenocarcinoma 13762 kill tumor in vitro and cause regression of tumor in vivo. The role of various host immune cells in CD4+ T-cell-mediated tumor elimination in vivo was investigated by adoptive transfer of anti-tumor T cell clones to recipients that were selectively depleted of individual immune cell types. By these means, macrophages and NK cells were found to be required for tumor killing. Depletion of host CD4+ T cells, CD8+ T cells, or neutrophils was without effect on tumor elimination by anti-tumor T cells. An essential role for antigen receptor-negative NK cells is likely dependent upon secretion of IFN-gamma from NK cells since treatment of tumor recipients with anti-IFN-gamma antibody prior to adoptive transfer and tumor challenge abrogated T cell killing, resulting in progressive tumor growth. Viability of adenocarcinoma 13762 or anti-tumor T cells was unaffected by treatment with either IFN-gamma or anti-IFN-gamma antibody in vitro, but cell surface MHC class II expression was induced in tumor cells by exposure to IFN-gamma. In addition, tumor cells were isolated from tumor-bearing animals by absorption using anti-MHC class II antibody, demonstrating that 13762 tumor expresses cell surface MHC class II antigens in situ. However, if hosts were depleted of NK cells before tumor challenge, MHC class II+ tumor was not recovered. Collectively these results suggest that adenocarcinoma 13762 is eliminated by MHC class II-restricted CD4+ T cells by direct tumor killing.

背景与目标： 与大鼠腺癌反应的CD4 + 抗肿瘤T细胞13762在体外杀伤肿瘤并在体内引起肿瘤的消退。通过将抗肿瘤T细胞克隆过继转移到选择性耗尽个体免疫细胞类型的受体，研究了各种宿主免疫细胞在体内CD4 T细胞介导的肿瘤消除中的作用。通过这些方法，发现巨噬细胞和NK细胞是杀死肿瘤所必需的。宿主CD4 T细胞，CD8 T细胞或中性粒细胞的耗竭对抗肿瘤T细胞消除肿瘤没有影响。抗原受体阴性NK细胞的重要作用可能取决于NK细胞中IFN-γ 的分泌，因为在过继转移和肿瘤挑战之前用抗IFN-γ 抗体治疗肿瘤接受者消除了T细胞杀伤，导致进行性肿瘤生长。腺癌13762或抗肿瘤T细胞的活力在体外不受IFN-γ 或抗IFN-γ 抗体治疗的影响，但细胞表面mhcii类表达通过暴露于IFN-γ 在肿瘤细胞中诱导。此外，通过使用抗MHC II类抗体吸收从荷瘤动物中分离肿瘤细胞，证明13762肿瘤原位表达细胞表面MHC II类抗原。但是，如果宿主在肿瘤激发之前耗尽了NK细胞，则MHC II类肿瘤将无法恢复。这些结果共同表明，通过直接杀伤肿瘤，MHC II类限制性CD4 T细胞消除了腺癌13762。

BACKGROUND & AIMS: The thymic microenvironment plays a key role in the intrathymic T-cell differentiation. It is composed of a tridimensional network of epithelial cells whose physiology is controlled by extrinsic circuits such as neuroendocrine axes. Herein we show that the expression of extracellular matrix ligands and receptor by cultured thymic epithelial cells is upregulated by prolactin (PRL) and growth hormone (GH), the latter apparently occurring via insulin-like growth factor I (IGF-I). Thymocyte release from the lymphoepithelial complexes, thymic nurse cells, as well as the reconstitution of these complexes are enhanced by PRL, GH or IGF-I. Treatment of a mouse thymic epithelial cell line with these hormones induced an increase in thymocyte adhesion, an effect significantly prevented in the presence of antibodies to fibronectin, laminin or respective receptors VLA-5 and VLA-6. Our data suggest that the in vitro changes in thymocyte/thymic epithelial cell interactions induced by pituitary hormones are partially mediated by the enhancement of extracellular matrix ligands and receptors.

背景与目标： 胸腺微环境在胸腺内T细胞分化中起关键作用。它由上皮细胞的三维网络组成，其生理受外部回路 (例如神经内分泌轴) 控制。在本文中，我们显示培养的胸腺上皮细胞的细胞外基质配体和受体的表达被催乳素 (PRL) 和生长激素 (GH) 上调，后者显然通过胰岛素样生长因子I (igf-i) 发生。PRL，GH或igf-i增强了从淋巴上皮复合物，胸腺护士细胞的胸腺细胞释放以及这些复合物的重建。用这些激素处理小鼠胸腺上皮细胞系诱导胸腺细胞粘附的增加，在存在针对纤连蛋白，层粘连蛋白或相应受体VLA-5和VLA-6的抗体的情况下，这种作用被显着阻止。我们的数据表明，垂体激素诱导的胸腺细胞/胸腺上皮细胞相互作用的体外变化部分是由细胞外基质配体和受体的增强介导的。

BACKGROUND & AIMS: :The hypoxic environment in tumor is reported to play an important role in pancreatic cancer progression. The interaction between stromal and cancer cells also contributes to the malignant behavior of pancreatic cancer. In the present study, we investigated whether hypoxic stimulation affects stromal as well as pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells, and invasiveness was thus further accelerated when the hypoxic PK8 cells were cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP activity and c-Met phosphorylation of PK8 cells were reduced by the removal of HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha expression was observed in surrounding stromal as well as pancreatic cancer cells, thus indicating hypoxia exists in both of cancer and stromal cells. Moreover, the stromal HGF expression was found to significantly correlate with not only the stromal HIF-1alpha expression but also the c-Met expression in cancer cells. These results indicate that the hypoxic environment within stromal as well as cancer cells activates the HGF/c-Met system, thereby contributing to the aggressive invasive features of pancreatic cancer.

背景与目标： : 据报道，肿瘤中的低氧环境在胰腺癌的进展中起重要作用。基质细胞和癌细胞之间的相互作用也有助于胰腺癌的恶性行为。在本研究中，我们调查了缺氧刺激是否会影响基质细胞以及胰腺癌细胞。我们的发现表明，缺氧显着提高了胰腺癌 (PK8) 和成纤维细胞 (MRC5) 的HIF-1alpha表达。低氧刺激加速了PK8细胞的侵袭活性，因此，当用低氧MRC5细胞制备的条件培养基 (低氧条件培养基) 培养低氧PK8细胞时，其侵袭能力进一步加快。缺氧条件下PK8细胞MMP-2、MMP-7、MT1-MMP和c-Met表达增加。低氧刺激还增加了MRC5细胞的肝细胞生长因子 (HGF) 分泌，导致PK8细胞中c-Met磷酸化升高。相反，通过从低氧条件培养基中去除HGF，可以降低PK8细胞的癌症侵袭，MMP活性和c-Met磷酸化水平。在免疫组织化学研究中，在周围基质以及胰腺癌细胞中观察到HIF-1alpha表达，因此表明癌症和基质细胞中都存在缺氧。此外，发现基质HGF表达不仅与癌细胞中的基质HIF-1alpha表达显着相关，而且与c-Met表达显着相关。这些结果表明，基质和癌细胞内的缺氧环境激活了HGF/c-Met系统，从而有助于胰腺癌的侵袭性特征。