Progressive loss of epidermal growth factor receptor in a subpopulation of breast cancers: implications in target-directed therapeutics

Understanding the molecular etiology and heterogeneity of disease has a direct effect on cancer therapeutics. To identify novel molecular changes associated with breast cancer progression, we conducted phosphoproteomics of the MCF10AT model comprising isogenic, ErbB2- and ErbB3-positive, xenograft-derived cell lines that mimic different stages of breast cancer. Using in vitro animal model and clinical breast samples, our study revealed a marked reduction of epidermal growth factor receptor (EGFR) expression with breast cancer progression. Such diminution of EGFR expression was associated with increased resistance to Gefitinib/Iressa in vitro. Fluorescence in situ hybridization showed that loss of EGFR gene copy number was one of the key mechanisms behind the low/null expression of EGFR in clinical breast tumors. Statistical analysis on the immunohistochemistry data of EGFR expression from 93 matched normal and breast tumor samples showed that (a) diminished EGFR expression could. be detected as early as in the preneoplastic lesion (ductal carcinoma in situ) and this culminated in invasive carcinomas; (b) EGFR expression levels could distinguish between normal tissue versus carcinoma in situ and invasive carcinoma with high statistical significance (P

Imitating micelles as a way to control coordination self-assembly: cage-polymer switching directed rationally by solvent polarity or pH

Disguising a metal complex as a micelle by using amphiphilic phosphine ligands enables it to switch between a coordination polymer and a discrete cage in response to solvent polarity or pH; this medium-dependent behaviour of the complex is rational because it parallels that of true micelles.

Structural similarity of directed universal hierarchical graphs: A low computational complexity approach

In the present paper we mainly introduce an efficient approach to measure the structural similarity of so called directed universal hierarchical graphs. We want to underline that directed universal hierarchical graphs can be obtained from generalized trees which are already introduced. In order to classify these graphs, we state our novel graph similarity method. As a main result we notice that our novel algorithm has low computational complexity. (c) 2007 Elsevier Inc. All rights reserved.

Anion-templated formation of a unique inorganic 'super-adamantoid' cage [Ag-6(triphos)(4)(O3SCF3)(4)](2+) [triphos = (PPh2CH2)(3)CMe]

In the presence of templating anions, 2:3 molar mixtures of triphos and silver(I) cations unexpectedly give novel hexanuclear cages, which result from an unusual 'endo-methyl' geometry of the triphos ligands.

Synthesis of a tri(organoplatinum) complex via the double directed lithiation of a mono(organoplatinum) precursor

The new diarylplatinum complex Cis-[Pt(PEt(3))(2){C6H3(CH(2)NMe(2))(2)-3,5}(2)] 1, containing four free amine coordination sites, undergoes directed lithiation with Bu(t)Li and subsequent transmetallation with [PtCl2(SEt(2))(2)] to give a triplatinum species 3 which reductively eliminates the diplatinum complex[ClPt{2,6-(Me(2)NCH(2))(2)C6H2-C6H2(CH(2)NMe(2))(2)-2,6}PtCl] 4.

Direct Quantification of Inorganic Polyphosphate in Microbial Cells Using 4 '-6-Diamidino-2-Phenylindole (DAPI)

Inorganic polyphosphate (polyP) is increasingly being recognized as an important phosphorus sink within the environment, playing a central role in phosphorus exchange and phosphogenesis. Yet despite the significant advances made in polyP research there is a lack of rapid and efficient analytical approaches for the quantification of polyP accumulation in microbial cultures and environmental samples. A major drawback is the need to extract polyP from cells prior to analysis. Due to extraction inefficiencies this can lead to an underestimation of both intracellular polyP levels and its environmental pool size: we observed 23-58% loss of polyP using standard solutions and current protocols. Here we report a direct fluorescence based DAPI assay system which removes the requirement for prior polyP extraction before quantification. This increased the efficiency of polyP detection by 28-55% in microbial cultures suggesting quantitative measurement of the intracellular polyP pool. It provides a direct polyP assay which combines quantification capability with technical simplicity. This is an important step forward in our ability to explore the role of polyP in cellular biology and biogeochemical nutrient cycling.

Enantioselective formal total synthesis of the Dendrobatidae frog toxin, (+)-pumiliotoxin B, via O-directed alkyne free radical hydrostannation

Herein we describe our application of the O-directed free radical hydrostannation of disubstituted alkyl-acetylenes (with Ph3SnH and Et3B) to the (+)-pumiliotoxin B total synthesis problem. Specifically, we report on the use of this method in the synthesis of the Overman alkyne 8, and thereby demonstrate the great utility of this process in a complex natural product total synthesis setting for the very first time. We also report here on a new, stereocontrolled, and highly practical enantioselective pathway to Overman's pyrrolidine epoxide partner 9 for 8, which overcomes the previous requirement for use of preparative HPLC to separate the 1:1 mixture of diastereomeric epoxides that was obtained in the original synthesis of 9.

Influence of molten-state annealing on the phase structure and crystallization behaviour of high impact polypropylene copolymer

The phase structure evolution of high impact polypropylene copolymer (IPC) during molten-state annealing and its influence on crystallization behaviour were studied. An entirely different architecture of the IPC melt was observed after being annealed, and this architecture resulted in variations of the crystallization behaviour. In addition, it was found that the core-shell structure of the dispersed phase was completely destroyed and the sizes of the dispersed domains increased sharply after being annealed at 200 degrees C for 200 min. Through examination of the coarseness of the phase morphology using phase contrast microscopy (PCM), it was found that a co-continuous structure and an abnormal 'sea-island' structure generally appeared with an increase in annealing time. The original matrix PP component appeared as a dispersed phase, whereas the copolymer components formed a continuous 'sea-island' structure. This change is ascribed to the large tension induced by solidification at the phase interface and the great content difference between the components. When the temperature was reduced the structure reverted to its original form. With increasing annealing time, the spherulite profiles became more defined and the spherulite birefringence changed from vague to clear. Overall crystallization rates and nucleation densities decreased, but the spherulite radial growth rates remained almost constant, indicating that molten-state annealing mainly affects the nucleation ability of IPC, due to a coarsened microstructure and decreased interface area. (C) 2011 Elsevier Ltd. All rights reserved.