Loss of E-cadherin is a key initial step in the transdifferentiation of epithelial cells to a mesenchymal phenotype, which occurs when tumor epithelial cells invade into surrounding tissues. Expression of the nuclear factor ZEB1 induces an epithelial-to-mesenchymal transition and confers a metastatic phenotype on carcinomas by repressing the E-cadherin gene at the transcriptional level.In this study, we show that ZEB1 interacts with the SWI/ SNF chromatin-remodeling protein BRG1 to regulate E-cadherin independently of CtBP, its traditional corepressor. Blocking the interaction between ZEB1 and BRG1 induces expression of E-cadherin and downregulation of the mesenchymal marker vimentin. ZEB1 and BRG1 colocalize in E-cadherin-negative cells from cancer lines and in the stroma of normal colon. Colocalization of ZEB1 and BRG1 in epithelial cells is only found in those de-differentiated cells characterized by nuclear b-catenin staining at the invasive edge of the tumor. Our results identify ZEB1/BRG1 as a new transcriptional mechanism regulating E-cadherin expression and epithelial-to-mesenchymal transdifferentiation that may be involved during the initial stages of tumor invasion.

The synthesis of five novel cyclometalated platinum(II) compounds containing five different alkynyl-chromophores was achieved by the reaction of the previously synthesized Pt−Cl cyclometalated compound (1) with the corresponding RCCH by a Sonogashira reaction. It was observed that the spectral and photophysical characteristics of the cyclometalated platinum(II) complexes (Pt−Ar) are essentially associated with the platinum-cyclometalated unit. Room-temperature emission of the Pt−Ar complexes was attributed to phosphorescence in agreement with DFT calculations. Broad nanosecond (ns)-transient absorption spectra were observed with decays approximately identical to those obtained from the emission of the triplet state. From the femtosecond-transient absorption (fs-TA) data, two main excitedstate decay components were identified: one in the order of a few picoseconds was assigned to fast intersystem crossing to populate the triplet excited-state and the second (hundreds of ns) was associated with the decay of the transient triplet state. In general, efficient singlet oxygen photosensitization quantum yields were observed from the triplet state of these complexes.

New [C,N,N′]-cyclometallated platinum(ii) and platinum(iv) complexes are prepared and their emission properties are reported.

Two series of Pt(II)-cyclometallated compounds containing N^C^N tridentate and alkynyl-chromophore ligands have been synthesized and structurally characterized. The N^C^N ligands differ on the presence of R 1 = H or F in the central aromatic ring, while six different chromophores have been introduced to the alkynyl moiety. Single-crystal X-ray structures for some of the compounds reveal the presence of weak intermolecular contacts responsible for the formation of some dimers or aggregates. The photophysical characterization shows the presence of two emission bands in solution assigned to the 3 π−π* transition from the N^C^N ligands mixed with 3 MLCT/ 3 ILCT transitions (higher energy band) in deaerated samples. The formation of excimers has also been identified as a broad band at longer wavelengths [near-infrared (NIR) emission] that becomes the main emission band for compounds containing phenanthrene as the chromophore. NIR emission behavior has also been explored using acetonitrile/water mixtures, and the presence of aggregates that emit at ca. 650 nm has also been detected.

Platinum-based chemotherapy persists to be the only effective therapeutic option against aw idev ariety of tumours. Nevertheless, the acquisition of platinum resistance is utterly common,ultimately cornering conventional platinum drugs to only palliative in many patients. Thus, encounteringa lternatives that are both effective and non-cross-resistant is urgent. In this work, we report the synthesis, reductions tudies, and luminescent properties of as eries of cyclometallated (C,N,N')Pt IV compounds derivedfrom amine-imine ligands, and their remarkable efficacy at the high nanomolar range and complete lack of cross-resistance, as an intrinsic property of the platinacycle, against multiplatinum-resistantc olorectal cancer (CRC) and castration-resistant prostate cancer( CRPC) metastatic cell lines generated for this work. We have also determined that the compounds are effectivea nd selective for ab roader cancer panel,i ncludingb reast and lung cancer.A dditionally,s elected compounds have been further evaluated, findingashift in their antiproliferative mechanism towards more cytotoxic and less cytostatic than cisplatin against cancerc ells, being also able to oxidize cysteine residues andi nhibit topoisomerase II, thereby holding great promise as future improved alternatives to conventional platinum drugs.Platinum-based chemotherapy is often the only effective treatment against ab road spectrumo ft umors,even if their success is limited by side-effects and resistance. OctahedralP t IV compounds have been shown to be av ery promising kindo fp rodrugss ince they are kinetically inert compared to Pt II analoguesa nd the two extra coordination positions allow the tuningo ft heir properties. [1][2][3][4] In particular,m ultiple action Pt IV prodrugs derived from cisplatin have attracted mucha ttention in recent years. [5][6][7] On the other hand,c yclometallated Pt II compounds containing bidentate (C,N) or tridentate (C,N,N')l igands display interestingp roperties. [8][9][10] Thep resence of a s(PtÀC) bond increases the stabilityo ft hese compounds, thus allowingt hem to reach the cell unaltered. In addition, covalent coordinationt o DNA is favoured since the strong PtÀCb ondi ncreasest he lability of the ligand in a trans position. Moreover,t he presence of aromatic planarg roups might favour intercalative binding to DNA through noncovalent p-p stacking interactions. Furthermore, several cyclometallatedP t II anticancer agentse xhibit luminescence properties which make them potential luminescent probesf or DNA in living cells and also allows easy tracing of their cellular uptake and distribution by fluorescencem icroscopy. [11,12] Surprisingly,l ittle attention has been devoted to [a] A.

Injuries to the superior gluteal nerve are very bad complications in hip surgery. An exact knowledge of its course may be helpful in avoiding such problems. Nineteen half pelvises from ten male and female adult cadavers were dissected. Dissections revealed that the nerve divided into two (89.48%) or three (10.52%) branches after leaving the pelvis. The more caudal branch was responsible for innervation of tensor fascia latae. The distance and the angle from the entry points of all branches of the superior gluteal nerve into the deep surface of the gluteus medium and minimus muscles to the mid-point of the superior border of the greater trochanter were measured. The branch that innerved the tensor fascia latae was also followed. These data were subjected to several statistical tests. Based on these findings, and in order to prevent nerve damage, we propose to define a 2-3 cm safe area above the great trochanter.

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