Discordance Rate of HER2 Status in Primary Gastric Carcinomas and Synchronous Lymph Node Metastases: A Multicenter Retrospective Analysis

Background: The assessment of human epidermal growth factor receptor 2 (HER2) gene amplification is essential in order to identify those patients affected by advanced gastric cancer who may benefit from Trastuzumab targeted therapy. Materials and Methods: With the aim to investigate the concordance rate in HER2 status between primary gastric carcinoma (GC) and synchronous lymphnode metastases, we investigated HER2 status in a cohort of 108 surgical formalin-fixed paraffin-embedded specimens of GC and matched synchronous metastatic lymph nodes collected from three different units of Anatomic Pathology in southern of Italy. Fleiss-Cohen weighted k statistics were used to assess the concordance rate of HER2 status. Results: HER2 amplification was observed in 17% of primary GCs and the overall concordance rate with corresponding nodal metastases was 90.74%. Changes in HER2 status between primary GC and matched synchronous metastases were evidenced in 10 (9.26%) cases. Of these, 6 cases were HER2 amplified in the primary GC and not amplified in the metastases, while 4 were HER2 not amplified in the primary tumour and amplified in the lymph node metastases. Conclusions: Although at present the simultaneous determination of HER2 in advanced gastric cancer and corresponding metastatic lymph nodes is not mandatory, the possibility that the synchronous metastases of GC have a different HER2 status from that of the primary tumour is of remarkable significance; Indeed this may have influence on the therapeutic management and prognosis of the patients.     

Fluoro-functionalized PLA polymers as potential water-repellent coating materials for protection of stone

A series of sixteen fluoro-functionalized poly(lactic acid)s were synthesised using two commercial fluorinated alcohols [3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octanol and 4-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)benzyl alcohol] as co-initiators in the ring-opening polymerization of L-lactide and rac-lactide (the racemic mixture of L- and D-lactide) catalyzed by Tin(II) 2-ethylhexanoate. The polymers were characterized by NMR, IR, GPC, DSC and tested as potential protective coating for stone. The performances were comparatively evaluated in terms of water protection efficacy and colour changes of the treated stone. Furthermore, the photo-stability of nine selected polymers under Solar Box condition was also investigated. It has been shown that the presence of fluorine makes the stone more water-repellent. The polymers showed also interesting photo-stability and some of them provided a behavior close to PLA-FLK-PLA block copolymers recently reported in the literature, in spite of their lower fluorine content © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

One‐Step Catalytic Enantioselective α‐Quaternary 5‐Hydroxyproline Synthesis: An Asymmetric Entry to Highly Functionalized α‐Quaternary Proline Derivatives

The highly enantioselective cascade reaction between N‐protected α‐cyanoglycine esters and α,β‐unsaturated aldehydes is disclosed. The reaction represents a one‐step entry to polysubstituted 5‐hydroxyproline derivatives having a quaternary α‐stereocenter generally in high yields with up to >95:5 dr and 99:1 er. It is also a direct catalytic two‐step entry to functionalized α‐quaternary proline derivatives.     

PEGylated chitosan derivatives: Synthesis, characterizations and pharmaceutical applications

This review sets out to describe and discuss the synthetic approaches and the fields of application of PEGylated chitosan copolymers especially for medical use. The PEGylation of chitosan and chitosan derivatives is able to add new physicochemical properties to the cationic polysaccharide polymers, thereby overcoming some limitations, especially regarding their solubility and their use in drug and gene delivery (DNA and siRNA). All methods of derivatization have been considered and described together with the different methods of characterization of the copolymers. The capacities of PEGylated chitosan to reduce chitosan toxicity, to enhance membrane permeation and to form thermosensitive hydrogels have also been discussed.     

Symmetry properties and bifurcation analysis of a class of periodically forced chemical reactors

In this work, we discuss how periodic forcing may induce symmetry properties into mathematical models of chemical reactors. We define a class of reactors subjected to discontinuous periodic forcing, and show that all the reactors belonging to this class have spatio-temporal symmetry. This symmetry and its influence on the possible bifurcation scenarios are discussed. The bifurcation analysis is carried out with suitable discrete systems that exploit a property of the Poincaré map. In fact, it is shown that the spatio-temporal symmetry induced by the forcing makes the Poincaré map of the continuous system an iterate of another map. On this basis, a technique to implement parameter continuation methods is proposed. With such a technique, it is also possible to characterize symmetric and nonsymmetric regimes and unstable limit sets otherwise undetected with “bruteforce” approaches. Examples for reverseflow reactors and networks of n-reactors with periodically switched feed and discharge positions are presented.     

Evidence for Bulk Residual Stress Strengthening in Al2O3/SiC Nanocomposites

The fracture behavior of Al₂O₃/SiC nanocomposites has been studied as a function of the SiC volume fraction and compared to that of the pure Al₂O₃ matrix. A pronounced strengthening effect was only observed for materials with low SiC content (i.e., ≤10 vol%) although no evidence of concurrent toughening was found. Assessment of near-tip crack opening displacement (COD) could not experimentally substantiate significant occurrence of an elastic crack-bridging mechanism, in contrast with a recently proposed literature model. Quantitative fractography analysis indicated that transgranular crack propagation in Al₂O₃/SiC nanocomposites depends on the location of the SiC dispersoids within the matrix texture; the higher the fraction of transgranularly located dispersoids, the more transgranular the fracture mode. Experimental evidence of remarkably high residual stresses arising from thermal dilatation mismatch (upon cooling) between Al₂O₃ and SiC phases were obtained by fluorescence and Raman spectroscopy. A strengthening mechanism is invoked which merely arises from residual stress through strengthening of Al₂O₃ grain boundaries.     

A cyclic CCK8 analogue selective for the cholecystokinin type A receptor: design, synthesis, NMR structure and binding measurements

A cyclic CCK8 analogue, cyclo(29,34)[Dpr(29),Lys(34)]-CCK8 (Dpr=L-2,3-diaminopropionic acid), has been designed on the basis of the NMR structure of the bimolecular complex between the N-terminal fragment of the CCK(A) receptor and its natural ligand CCK8. The conformational features of cyclo(29,34)[Dpr(29),Lys(34)]-CCK8 have been determined by NMR spectroscopy in aqueous solution and in water containing DPC-d(38) micelles (DPC=dodecylphosphocholine). The structure of the cyclic peptide in aqueous solution is found to be in a relaxed conformation, with the backbone and Dpr29 side chain atoms making a planar ring and the N-terminal tripeptide extending approximately along the plane of this ring. In DPC/water, the cyclic peptide adopts a "boat-shaped" conformation, which is more compact than that found in aqueous solution. The cyclic constraint between the Dpr29 side chain and the CCK8 carboxyl terminus (Lys34) introduces a restriction in the backbone conformational freedom. However, the interaction of cyclo(29,34)[Dpr(29),Lys(34)]-CCK8 with the micelles still plays an important role in the stabilisation of the bioactive conformation. A careful comparison of the NMR structure of the cyclic peptide in a DPC micelle aqueous solution with the structure of the rationally designed model underlines that the turn-like conformation in the Trp30-Met31 region is preserved, such that the Trp30 and Met31 side chains can adopt the proper spatial orientation to interact with the CCK(A) receptor. The binding properties of cyclo(29,34)[Dpr(29),Lys(34)]-CCK8 to the N-terminal receptor fragment have been investigated by fluorescence spectroscopy in a micellar environment. Estimates of the apparent dissociation constant, K(d), were in the range of 70-150 nM, with a mean value of 120+/-27 nM. Preliminary nuclear medicine studies on cell lines transfected with the CCK(A) receptor indicate that the sulfated-Tyr derivative of cyclo(29,34)[Dpr(29),Lys(34)]-CCK8 displaces the natural ligand with an IC(50) value of 15 microM.     

Synthesis and characterization of epoxidized styrene–butadiene rubber/silicon dioxide hybrid materials

Hybrid materials were synthesized from epoxidized (68, 43, or 14%) styrene–butadiene rubber (SBR) and the hydrolysis product of tetraethoxysilane (TEOS) in situ under ultrasonic irradiation. The products were characterized with thermal analysis (differential scanning calorimetry and thermogravimetric analysis), stress–strain tests, scanning electron microscopy (including energy‐dispersive spectrometry), and swelling in tetrahydrofuran and water. The most transparent were those prepared from SBR with the highest degree of epoxidation, whereas those obtained from less epoxidized SBR and with larger amounts of TEOS showed distinct phases that could be considered two hybrid phases (one rich in TEOS and another rich in SBR). © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 798–803, 2004