Genomic Deregulation of the E2F/Rb Pathway Leads to Activation of the Oncogene EZH2 in Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a highly aggressive lung neoplasm with extremely poor clinical outcomes and no approved targeted treatments. To elucidate the mechanisms responsible for driving the SCLC phenotype in hopes of revealing novel therapeutic targets, we studied copy number and methylation profiles of SCLC. We found disruption of the E2F/Rb pathway was a prominent feature deregulated in 96% of the SCLC samples investigated and was strongly associated with increased expression of EZH2, an oncogene and core member of the polycomb repressive complex 2 (PRC2). Through its catalytic role in the PRC2 complex, EZH2 normally functions to epigenetically silence genes during development, however, it aberrantly silences genes in human cancers. We provide evidence to support that EZH2 is functionally active in SCLC tumours, exerts pro-tumourigenic functions in vitro, and is associated with aberrant methylation profiles of PRC2 target genes indicative of a “stem-cell like” hypermethylator profile in SCLC tumours. Furthermore, lentiviral-mediated knockdown of EZH2 demonstrated a significant reduction in the growth of SCLC cell lines, suggesting EZH2 has a key role in driving SCLC biology. In conclusion, our data confirm the role of EZH2 as a critical oncogene in SCLC, and lend support to the prioritization of EZH2 as a potential therapeutic target in clinical disease.     

NGF and other growth factors induce an association between ERK1 and the NGF receptor, gp140prototrk.

As detected by coimmunoprecipitation from PC12 cells, NGF induces rapid association between ERK1 (a growth factor-activated serine/threonine protein kinase) and gp140prototrk NGF receptors. In contrast, no such association is found with the closely related ERK2. Anti-trk immunocomplexes generated from NGF-treated cells also contain protein kinase activity that shares many properties with soluble ERK1. The association of both ERK1 protein and ERK-like kinase activity with gp140prototrk is maximal by 5 min of NGF treatment, persists for approximately 1 hr, and subsequently declines by 18 hr. Treatment with either basic fibroblast growth factor, epidermal growth factor, or orthovanadate also leads to association of ERK1 with gp140prototrk without tyrosine phosphorylation of the latter. The interaction between ERK1 and gp140prototrk may prove relevant to the NGF mechanism.     

Conceptual design of a cellular filter to remove trace viral contaminants in blood.

Various process alternatives and designs of using a filter containing cellular adsorbents to remove trace viral contaminants from blood and other protein solutions have been studied. Sterilization charts have been developed that can be used to estimate the filter size required to achieve a desired sterilization criterion. A parametric study was carried out to identify various process parameters that may affect this physical trace removal process. It has been demonstrated that the adsorption rate constant is a critical parameter in the design of an efficient cellular filter for viral contaminant removal. This constant is characteristic of the virus-cell system under consideration and is shown to be particularly sensitive to the cell surface receptor density, adsorbent diameter, and fluid flow rate. Higher log titer reduction in virus concentrations can be achieved with low flow rates and no recycle. Preliminary analyses indicate the feasibility of using a magnetically stabilized fluidized filter (MSFF) reactor design for effective virus removal from these complex solutions.     

高陵土性狀的檢定

高陵土一名高嶺土,就是陶土,俗名白土子。主要成份为含水矽酸鋁(OH)_8Al_4 Si_4 O_(10)。由風化长石及石英二部分构成。盛产我国,瓷器原料。工业上用作填充剂的也很多。最近合成杀蟲剂应用方面又用牠来作稀释剂。本文的目的就在把高陵土主要的性状作一个檢定,以便明瞭牠的优点和缺点。     

用苏芸金杆菌孢子粉於防治玉米螟

在1953年用叶心灌药以防治玉米螟的春玉米小区试验中,作者等有意识地使用了细菌学家孟雨同志自法国带回的苏芸金杆菌孢子粉(内含孢子约1/10,余为大豆粉)。它们被稀释到1:2000,1:10000和1:20000三个等级(据孟同志谈:这个稀释量是过於低了)。     

TNFalpha-induced cyclooxygenase 2 not only increases the vasopermeability of blood-brain barrier but also enhances the neutrophil survival in Escherichia coli-induced brain inflammation.

In Escherichia coli-induced brain inflammation, cyclooxygenase-2 was induced not only on brain arterioles at 3 h, but also on infiltrating neutrophils at 9 h post-intracerebral injection. Intravenous injection of E. coli or recombinant TNFalpha also induced cyclooxygenase-2 expression on arterioles. Cyclooxygenase-2 and TNFalpha were co-localized on the arterioles as well as the infiltrating neutrophils by serial-section staining, indicating that cyclooxygenase-2 was induced by TNFalpha. NS398 (a cyclooxygenase-2 selective inhibitor) not only inhibited the increase of blood-brain barrier permeability, but also enhanced the apoptosis of the infiltrating neutrophils after E. coli stimulation. This suggests that TNFalpha-stimulated cyclooxygenase-2 induction play an important role on E. coli-induced brain inflammation. Its inhibition would help the resolution of neutrophil-mediated brain inflammation.     

植物体内的钙信使系绕

Ca对植物不仅仅是一种大量营养元素,更重要的是作为偶连胞外信号与胞内生理生化反应的第二信使,作为植物代谢和发育的主要调控者。本文介绍了Ca在植物细胞中的分布及其体内平衡机制,以及Ca2+信使系统调控的植物生理生化过程,讨论了外界信号通过Ca2+信使系统的传递和表达过程,Ca2+信使系统对基因表达的可能影响,以及Ca2+信使系统的作用机制,并提出了今后的研究方向。