The two most common histological subtypes of malignant germ cell tumour are distinguished by global microRNA profiles, associated with differential transcription factor expression.

BACKGROUND: We hypothesised that differences in microRNA expression profiles contribute to the contrasting natural history and clinical outcome of the two most common types of malignant germ cell tumour (GCT), yolk sac tumours (YSTs) and germinomas. RESULTS: By direct comparison, using microarray data for paediatric GCT samples and published qRT-PCR data for adult samples, we identified microRNAs significantly up-regulated in YSTs (n = 29 paediatric, 26 adult, 11 overlapping) or germinomas (n = 37 paediatric). By Taqman qRT-PCR we confirmed differential expression of 15 of 16 selected microRNAs and further validated six of these (miR-302b, miR-375, miR-200b, miR-200c, miR-122, miR-205) in an independent sample set. Interestingly, the miR-302 cluster, which is over-expressed in all malignant GCTs, showed further over-expression in YSTs versus germinomas, representing six of the top eight microRNAs over-expressed in paediatric YSTs and seven of the top 11 in adult YSTs. To explain this observation, we used mRNA expression profiles of paediatric and adult malignant GCTs to identify 10 transcription factors (TFs) consistently over-expressed in YSTs versus germinomas, followed by linear regression to confirm associations between TF and miR-302 cluster expression levels. Using the sequence motif analysis environment iMotifs, we identified predicted binding sites for four of the 10 TFs (GATA6, GATA3, TCF7L2 and MAF) in the miR-302 cluster promoter region. Finally, we showed that miR-302 family over-expression in YST is likely to be functionally significant, as mRNAs down-regulated in YSTs were enriched for 3' untranslated region sequences complementary to the common seed of miR-302a~miR-302d. Such mRNAs included mediators of key cancer-associated processes, including tumour suppressor genes, apoptosis regulators and TFs. CONCLUSIONS: Differential microRNA expression is likely to contribute to the relatively aggressive behaviour of YSTs and may enable future improvements in clinical diagnosis and/or treatment.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Titanium and zirconium complexes with sterically hindered aryl-substituted iminophosphoranato ligands

The benzyliminophosphorane 4-ButC6H4CH2P(Ph)2==NC6H2Me3-2,4,6 reacted with TiCl4 or ZrCl4 to give the N-donor adducts, MCl4{4-ButC6H4CH2P(Ph)2==NC6H2Me3-2,4,6}. Whereas the zirconium compound proved unreactive, solutions of the titanium analogue at 10–20 °C slowly underwent C–H activation to give the phosphoranato complex TiCl3{4-ButC6H4CHP(Ph)2==NC6H2Me3-2,4,6}. The trichloro complexes MCl3{4-ButC6H4CHP(Ph)2==NC6H2Me3-2,4,6} were also accessible from Li[4-ButC6H4CHP(Ph)2==NC6H2Me3-2,4,6] and MCl4 (M = Ti or Zr). The reaction of 4-ButC6H4CH2P(Ph)2==NC6H2Me3-2,4,6 with Zr(NMe2)4 in refluxing toluene led to Zr(NMe2)3{4-ButC6H4CHP(Ph)2==NC6H2Me3-2,4,6}. The compound is fluxional in solution. Treatment with an excess of Me3SiCl led to silylation of the ligand to give ZrCl4{4-ButC6H4CH(SiMe3)P(Ph)2==NC6H2Me3-2,4,6}. The structures of 4-ButC6H4CH2P(Ph)2==NC6H2Me3-2,4,6 and Zr(NMe2)3{4-ButC6H4CHP(Ph)2==NC6H2Me3-2,4,6} were determined by X-ray diffraction

B(C6F5)3 as aC6F5 transfer reagent in zirconium chemistry: facileformation of the borole-bridged triple-decker complex[Zr2Cp″2(C6F5)2{μ-η5∶η5-C4H4BCH2-η3,κF-CHCHCHB(C6F5)3}]

Warming mixtures of (CpR)Zr(?3-C4H7)(? 4-C4H6) and B(C6F5)3 leads to complete transfer of all three C6F5 substituents of a B(C6F5)3 molecule to give borole-bridged triple-decker complexes with a Zr2C4B core, a zwitterionic structure and an unusually strong Zr–F donor interaction

Synthesis and characterization of dicarboranylmethylammonium polyoxometallates

The reaction of [C2B10H11CH2NH3]Cl (3) with [NH4]6[Mo7O24][H2O]4 in water instantly afforded a white precipitate: crystallization from acetone–hexane thence gave the hybrid dicarborane octamolybdate salt, [C2B10H11CH2NH3]2[C2B10H11CH2NH=CMe2]2[Mo8O26][Me2CO]4.5 (5), whereas crystallization from acetonitrile–ether gave three further salts: [C2B10H11CH2NH3]2[C2B10H11CH2NH2CHMe2]2[Mo8O26][MeCN]2 (6), [C2B10H11CH2NH3]4[Mo8O26][MeCN]2[Et2O]2 (7) and [C2B10H11CH2NH3]2[C2B10H11CH2NH2Et]2[Mo8O26][MeCN]2 (8). Similarly, treatment of an acidified solution of Na2WO4 with [C2B10H11CH2NH3]Cl (3) in water also yielded a white precipitate: crystallization from acetone–hexane afforded the salt [C2B10H11CH2NH=CHMe2]4[W10O32][H2O]2[Me2CO]4 (10), whereas crystallization from acetonitrile–ether gave the double salt [C2B10H11CH2NH3]2[C5H5NH]2[W10O32][MeCN]2-[Et2O] (11). All these ‘globule–globule’ salts 5, 6, 8, 10 and 11 have been characterized by single-crystal X-ray diffraction analyses. Crystal structures reveal the presence of various small solvate molecules, together with an extensive network of hydrogen bonds between ammonium groups and oxygen atoms of the isopolyoxometallates. The isopropyl substituent in one of the carborane cations of the salts 6 and the ethyl substituent in one of the carborane cations of salts 8 may result from occluded isopropanol and ethanol in the starting salt 3 with alkylations of the primary ammonium group being assisted by isopolymolybdate anions. The presence of the pyridinium cation in 11 is believed to arise from contamination during work-up the reaction mixture.Peer reviewe

Synthetic, Reactivity, and Structural Studies on Borylcyclopentadienyl Complexes of Titanium: New CpB Titanocene Complexes with C−B−Cl, C−B−O, and C−B−N Bridges (CpB = η5-C5H4B(C6F5)2)

The (borylcyclopentadienyl)titanium complex (Cp-B)TiCl3 (1; Cp-B = eta(5)-C5H4B(C6F5)(2)) reacts with LiC5H5 (LiCp), LiC5H4SiMe3 (LiCP'), and LiC9H7 (LiInd) to give the titanocene complexes (Cp-B)CpTiCl2 (2), (Cp-B)Cp'TiCl2 (3), and (Cp-B)(Ind)TiCl2 (4), respectively. In contrast to 1, which possesses piano stool geometry with an uncoordinated, trigonal-planar borg moiety, the -B(C6F5)(2) substituents in 2-4 act as intramolecular Lewis acids by coordinating to chloride ligands, with formation of B-Cl-Ti bridges that have relatively short B-Cl and elongated Ti-Cl bonds. The compounds are fluxional, with the -B(C6F5)(2) moiety switching rapidly from one chloride ligand to the other (2: Delta G(double dagger) = 37 kJ mol(-1) (200 K)). Recrystallization of 2 in the presence of traces of moisture afforded (Cp-B)CpTi(mu-OH)Cl (5), with a rigid B-O-Ti chelate arrangement. Treatment of 1 with 1 or 2 equiv of LiHNCMe3 gives the binuclear titanium imido complexes [(Cp-B)TiCl(mu-NCMe3)](2) (7) and [(Cp-B)TiCl(mu-NCMe3). H2NCMe3](2) (8), respectively. These complexes are based on Ti2N2 rings but show no boron-imide interactions. In contrast, the reaction of 2 with LiNHCMe3 affords (Cp-B)CpTi(mu-NHCMe3)Cl (9), which exhibits a constrained-geometry type Cp-B-N arrangement. The crystal structures of 4, 5, 8, and 9 have been determined

Synthesis and reactivity of sterically hindered iminopyrrolato complexes of zirconium, iron, cobalt and nickel

The new bis(imino)pyrrole ligand 2,5-C4H2NH(CH==NC6H3Pri2)2 (HL1) reacts with Zr(NMe2)4 to give the 1:1 complex (L1)Zr(NMe2)3 (1), whereas the mono(imino)pyrrole 2-C4H3NH(CH==NC6H3Pri2) (HL2) substitutes two amido ligands to give (L2)2Zr(NMe2)2 (2). The lithium salt LiL1 reacts with ZrCl4 to give (L1)ZrCl2(µ-Cl)2Li(OEt2)2 (3), while the reaction of LiL2 with ZrCl4 or treating 2 with Me3SiCl gives (L2)2ZrCl2. Iron(II) chloride reacts with LiL1 to afford the bis(ligand) complex Fe(L1)2 (5), while only one pyrrolato ligand is incorporated on reacting LiL1 with CoCl2(thf) to give [Li(thf)4][CoCl2L1] (6a). On warming, 6a readily loses thf to give [Li(thf)2][CoCl2L1] (6b). By contrast, LiL2 reacts with CoCl2 and NiCl2 to give the halide-free complexes Co(L2)2 and Ni(L2)2, respectively. The crystal structures of HL1 and complexes 1, 2 and 5 are reported. In all cases the potentially tridentate ligand L1 is two-coordinate. Mixtures of the halide-free bis(ligand) complexes with methylaluminoxane do not show any activity for ethene polymerisation; however, 3 and 4 catalyse the polymerisation of ethene, while 6 has moderate activity for the oligomerisation of ethene and propene to linear and branched products