A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.     

Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis

Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the “anti-biotic era”. Although, we have expeditiously developed our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts required for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins.In this review article, we provide an overview of the established diagnostic techniques and therapeutics for keratitis caused by various bacteria. We extensively report the recent in-roads through novel tools for accurately diagnosing mono- and poly-bacterial corneal infections. Furthermore, we outline the recent progress by our groups and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discuss in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.     

来源于骨髓和脐带血的基质细胞基本特性的比较

目的比较骨髓与脐带血细胞体外培养基质细胞的基本特性,为基质细胞的选择应用提供依据.方法用Dexter长期培养体系培养骨髓和脐带血基质细胞,以细胞增殖、细胞形态、细胞化学染色、细胞表面及基质细胞支持另一骨髓细胞形成的鹅卵石造血区(CAFC),长期培养起始细胞(LTC-IC)为指标,比较两者的生长特性、成分及功能.结果①细胞生长特性:出现贴壁细胞时间,骨髓细胞为培养3d,脐带血细胞为培养5～6d;细胞融合成片时间,骨髓细胞为培养10～14d,脐带血细胞为培养12～18d;第21天细胞增殖数,骨髓比脐带血细胞增殖少;②细胞成分:21d培养后细胞成分,骨髓来源者以成纤维细胞为主,其次是巨噬细胞与内皮细胞,脂肪细胞最少;脐带血细胞来源者,以巨噬细胞为主,其次是内皮细胞、成纤维细胞,偶见脂肪细胞;细胞化学与上述结果基本一致;细胞表面抗原检测,CD14、CD45的表达骨髓细胞明显低于脐带血细胞;③细胞功能:骨髓来源的基质细胞较脐带血细胞的基质细胞支持另一骨髓细胞形成的CAFC和LTC-IC明显多.结论①生长特征:形成贴壁细胞时间骨髓较脐带血短,骨髓细胞比脐带血细胞有核细胞数增殖快、持续时间相对短;②细胞成分特性:骨髓来源形成的基质细胞以成纤维细胞为主,脐带血来源者以巨噬细胞为主;③细胞功能特性:骨髓细胞形成的贴壁细胞较脐带血细胞形成的贴壁细胞更利于CAFC、LTC-IC生长.     

丙丁酚对载脂蛋白E~(-/-)小鼠主动脉粥样硬化病变及病变处凝集素样氧化型低密度脂蛋白受体1表达的影响

目的观察丙丁酚对载脂蛋白E-/-小鼠主动脉粥样硬化斑块形成及主动脉凝集素样氧化型低密度脂蛋白受体1表达的影响,以探讨丙丁酚调节血脂以外的可能的抗动脉粥样硬化作用机制。方法将21只4周龄的雄性载脂蛋白E-/-小鼠随机分成基础饮食对照组、高脂饮食对照组和高脂饮食加丙丁酚组     

Papillary carcinoma of the thyroid with exuberant nodular fasciitis-like stroma

 We describe a rare case of papillary carcinoma with extensive proliferation of stromal cells. The stromal cells were immunocytochemically positive for vimentin, α-smooth muscle actin and desmin, but negative for cytokeratin, epithelial membrane antigen, S-100, thyroglobulin and CD34. These results and the ultrastructure of the stromal cells, which exhibited the characteristics of both fibroblasts and smooth muscle cells, indicated an origin from myofibroblasts. We conclude that myofibroblastic proliferation may contribute to the stromal response in the slow growth of the papillary carcinoma. Received: 29 August 1996 / 26 May 1997     

Effect of cortisone on cells at the bone-marrow interface

Summary A study of the association between the rate of proliferation of marrow fibroblast-like stromal cells (in vitro) and the rate of endosteal bone mineralization (EsMR) (in vivo) was undertaken in an osteopenic rat model. We report than 200 g male rats treated with cortisone acetate (5 mg/day for 7 days) exhibit decreases in marrow fibroblast colony-forming units (FCFU) and tetracycline-based measurements of EsMR at the level of the femoral midshaft. In cortisone-treated rats recovering for 1–3 weeks, the FCFU census and EsMR normalized during the first posttreatment week, remained at control levels after 2–3 weeks, and exhibited a relapse in the third week which signified only partial recovery. These changes were unrelated to patterns of body weight gain. The data indicate that the FCFU census can serve to index endosteal osteoblast vigor.     

CT结合内镜检查诊断胃肠道间质瘤的价值

目的：探讨CT结合内镜检查诊断胃肠道间质瘤(GIST)的价值。方法：回顾分析18例均经手术病理检验证实为GIST病人的CT及内镜检查资料。结果：(1)18例GIST的CT表现为类圆形或分叶状肿瘤，边界清楚，13例平扫及增强密度均匀，强化明显，5例瘤灶内有坏死液化区；肿瘤周围肠管不同程度受压移位或粘连。(2)15例源于胃、十二指肠及结肠的间质瘤均行内镜检查，4例瘤侧胃壁镜下所见黏膜呈外压性改变者未行咬检；11例伴有溃疡形成，溃疡处咬检获取病理组织。(3)18例均行手术后光镜观察及免疫组化检查，18例CD-117均为阳性，13例CD-34阳性，10例Vimentin阳性。结论：CT与内镜相结合检查，能提高胃、十二指肠及结肠GIST定位、定性的准确性。     

免疫调节剂对小鼠实验性单纯疱疹性角膜炎发病的影响

实验组小鼠腹腔分别注射免疫调节剂胸腺五肽(TP5)或环孢霉素(CsA),对照组注射生理盐水(NS),尔后角膜感染单纯疱疹病毒(HSV),造成小鼠实验性单纯疱疹性角膜炎模型。用裂隙灯显微镜观察小鼠角膜上皮、角膜实质、角膜新生血管、结膜和眼睑的病变变化情况。结果:种毒唇4～6天,TP5组角膜上皮和角膜实质病变比NS组严重,差异有显著性,而CsA无此作用。三组小鼠新生血管形成程度差异无显著性。且均在第8天出现高峰。TP5组和CsA组的结膜和眼睑病变,比NS组严重。因此,在临床上,应根据不同病种和不同情况,慎重使用免疫调节剂。