Reconstitution of the Turkey erythrocyte adenylate cyclase sensitivity to l-epinephrine upon re-insertion of the Lubrol solubilized components into phospholipid vesicles

Turkey erythrocyte adenylate cyclase was activated by GppNHp and l-epinephrine to its stable, highly active form. In this form the enzyme could be solubilized by Lubrol-PX and subsequently re-inserted into phospholipid vesicles concomitantly with the removal of up to 99.3% of the Lubrol. The ability of GTP and l-epinephrine to reverse the GppNHp/epinephrine activated state was taken as a measure for the reappearance of hormone sensitivity in the reconstituted vesicles. An incomplete but significant reappearance of hormone sensitivity in the reconstituted adenylate cyclase was achieved. This hormone sensitivity was found to be stereospecific for (?)epinephrine. The ¹²⁵I-cyanopindolol binding properties of the reconstituted β-receptor depend on the nature of the detergent and the phospholipids used in the reconstitution.     

Potential roles and targeted therapy of the CXCLs/CXCR2 axis in cancer and inflammatory diseases

The chemokine receptor CXCR2 and its ligands are implicated in the progression of tumours and various inflammatory diseases. Activation of the CXCLs/CXCR2 axis activates multiple signalling pathways, including the PI3K, p38/ERK, and JAK pathways, and regulates cell survival and migration. The CXCLs/CXCR2 axis plays a vital role in the tumour microenvironment and in recruiting neutrophils to inflammatory sites. Extensive infiltration of neutrophils during chronic inflammation is one of the most important pathogenic factors in various inflammatory diseases. Chronic inflammation is considered to be closely correlated with initiation of cancer. In addition, immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) against T cells attenuate the anti-tumour effects of T cells and promote tumour invasion and metastasis. Over the last several decades, many therapeutic strategies targeting CXCR2 have shown promising results and entered clinical trials. In this review, we focus on the features and functions of the CXCLs/CXCR2 axis and highlight its role in cancer and inflammatory diseases. We also discuss its potential use in targeted therapies.     

Imaging the interaction of αv integrin-GFP in osteosarcoma cells with RFP-expressing host stromal cells and tumor-scaffold collagen in the primary and metastatic tumor microenvironment

Human osteosarcoma 143B cells were previously stably transfected with an α_v integrin green flourescent protein (GFP) vector. 143B cells expressing α_v integrin-GFP were transplanted orthotopically in the tibia of transgenic nude mice ubiquitously expressing red fluorescent protein (RFP). The primary tumors acquired RFP-expressing stroma and were passaged orthotopically in the tibia in noncolored nude mice, which maintained the RFP stroma. The interaction of α_v integrin-GFP expression in 143B cells with RFP-expressing host stromal cells was observed by confocal microscopy using the Olympus FV1000. Collagen fibers were imaged simultaneously in reflectance mode. The RFP-expressing stroma included cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) which persisted even 3 weeks after passage to nontransgenic nude mice. CAFs expressing RFP were aligned between collagen fibers and cancer cells expressing α_v integrin-GFP. Six weeks after transplantation, pulmonary metastases expressing α_v integrin-GFP could be identified. TAMs expressing RFP accompanied metastasized osteosarcoma cells expressing α_v integrin-GFP in the lung. The current study demonstrates the importance of α_v integrin interaction with stromal elements in osteosarcoma.     

Insights into the role of components of the tumor microenvironment in oral carcinoma call for new therapeutic approaches

The research on oral cancer has focused mainly on the cancer cells, their genetic changes and consequent phenotypic modifications. However, it is increasingly clear that the tumor microenvironment (TME) has been shown to be in a dynamic state of inter-relations with the cancer cells. The TME contains a variety of components including the non-cancerous cells (i.e., immune cells, resident fibroblasts and angiogenic vascular cells) and the ECM milieu [including fibers (mainly collagen and fibronectin) and soluble factors (i.e., enzymes, growth factors, cytokines and chemokines)]. Thus, it is currently assumed that TME is considered a part of the cancerous tissue and the functionality of its key components constitutes the setting on which the hallmarks of the cancer cells can evolve. Therefore, in terms of controlling a malignancy, one should control the growth, invasion and spread of the cancer cells through modifications in the TME components. This mini review focuses on the TME as a diagnostic approach and reports the recent insights into the role of different TME key components [such as carcinoma-associated fibroblasts (CAFs) and inflammation (CAI) cells, angiogenesis, stromal matrix molecules and proteases] in the molecular biology of oral carcinoma. Furthermore, the impact of TME components on clinical outcomes and the concomitant need for development of new therapeutic approaches will be discussed.     

腹腔镜与传统开腹TME 在治疗中低位直肠癌的META 分析

目的:探讨腹腔镜行TME手术治疗中低位直肠癌的可行性。方法:检索2001年1月～2012年2月间发表的比较腹腔镜与经腹TME手术治疗中低位直肠癌的随机对照试验(RCT)及临床对照试验(CCT)论文,根据纳入排除标准纳入文献,提取临床指标,进行META分析。结果:最终有22项临床试验被纳入,两组患者的性别、年龄等基本特征均衡。两组腹腔出血(P=0.36)、吻合口漏(P=0.06)及肠梗阻(P=0.16)之间差异无统计学意义,腹腔镜组较传统开腹组总的并发症(P<0.0001)及切口感染发生率低(P=0.0006),手术时间长(P=0.001),术中出血量少(P<0.00001),术后肠道功能恢复时间早(P=0.0002),住院时间短(P<0.00001)。结论:LTME较OTME在中低位直肠癌手术中能够更安全的达到根治性切除的效果,而且在减少手术对患者的创伤方面具有优势。     

Reshaping of the tumor microenvironment by cellular senescence: An opportunity for senotherapies

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MDSCs在恶性肿瘤中的生物学作用及其研究进展

髓源抑制性细胞(myeloid-derived suppressor cells,MDSCs)是一群以骨髓祖细胞和未分化成熟的粒细胞、树突状细胞、巨噬细胞为代表的异质髓细胞,表达的抗原标志多样且不同于成熟髓细胞。当机体处于癌症、炎症、感染等状态时,MDSCs首先从骨髓被募集到外周并在外周被活化,一系列肿瘤来源的慢性炎症相关的因子是介导MDSCs的募集和活化的关键。MDSCs有多种方法抑制机体的获得性和天然抗肿瘤免疫,来帮助肿瘤细胞逃避机体的免疫监视和攻击,促进肿瘤发展。近年来,越来越多的研究者开始关注MDSCs与恶性肿瘤的相关性而且靶向MDSCs的肿瘤免疫治疗也见于报道。本文旨在对MDSCs在恶性肿瘤中的生物学作用及研究进展作一简要综述。     

Conformational transformation and selection of synthetic prion strains

Prion protein is capable of folding into multiple self-replicating prion strains that produce phenotypically distinct neurological disorders. Although prion strains often breed true upon passage, they can also transform or “mutate” despite being devoid of nucleic acids. To dissect the mechanism of prion strain transformation, we studied the physicochemical evolution of a mouse synthetic prion (MoSP) strain, MoSP1, after repeated passage in mice and cultured cells. We show that MoSP1 gradually adopted shorter incubation times and lower conformational stabilities. These changes were accompanied by structural transformation, as indicated by a shift in the molecular mass of the protease-resistant core of MoSP1 from approximately 19 kDa [MoSP1(2)] to 21 kDa [MoSP1(1)]. We show that MoSP1(1) and MoSP1(2) can breed with fidelity when cloned in cells; however, when present as a mixture, MoSP1(1) preferentially proliferated, leading to the disappearance of MoSP1(2). In culture, the rate of this transformation process can be influenced by the composition of the culture media and the presence of polyamidoamines. Our findings demonstrate that prions can exist as a conformationally diverse population of strains, each capable of replicating with high fidelity. Rare conformational conversion, followed by competitive selection among the resulting pool of conformers, provides a mechanism for the adaptation of the prion population to its host environment.     

野生经济植物资源橡籽仁可利用价值的研究

以京白种鸡作鸡作试验动,以玉米、稻谷作对照,采用鸡真代谢能（ＴＭＥ）法研究野生经济植物资源橡胶籽仁的可利用营养价值。结果表明,橡籽仁１ｋｇ含量总能（ＧＥ）１６．５３ＭＪ,表观代谢能（ＡＭＥ）１１．１３ＭＪ,真代谢能（ＴＭＥ）１１．６６ＭＪ,,含粗蛋白（ＣＰ）１０．６３％,ＣＰ的表观利用率（ＣＰＡＡ）４５．５５％,真利用率（ＣＰＴＡ）４９．８３％,１７种氨基酸（ＡＡ）总含量９．２３％,必需氨基酸（Ｅ     

Phospholipid methylation in MOPC-31C cell membranes with modified phospholipid composition

The presence of the methylation pathway from phosphatidylethanolamine to phosphatidylcholine was first shown in MOPC-31C cells. Intermediate phospholipids of this pathway, phosphatidyl-N-monomethylethanolamine and phosphatidyl-N,N′-dimethylethanolamine, were accumulated in the cell membranes by adding choline analogues such as N-monomethylethanolamine and N,N′-dimethylethanolamine to the culture medium. These modified membranes had a striking character of enhanced phospholipid methylation. This enhancement could be explained by increases in the second and the third step of the methylation pathway from phosphatidylethanolamine.