Androgen-dependent mammary carcinogenesis in rats transgenic for the Neu proto-oncogene

AbstractTransgenic rats were created with overexpression of the Neu proto-oncogene in the mammary gland of both sexes, yet only males developed mammary cancer in an androgen-dependent fashion. Transgenic females only developed mammary cancer if treated with androgens. These tumors were positive for androgen receptor (AR), but negative for estrogen and progesterone receptors. Extensive analysis failed to detect mutations anywhere within the neu transgene from mammary carcinomas. Established mammary carcinomas eventually escaped their dependency on androgens. Transgenic long-term gonadectomized rats did not develop mammary cancer, but Neu overexpression stimulated the growth of their mammary glands. Our results suggest crosstalk between the Neu proto-oncogene and AR signaling pathways in the growth of both the normal and cancerous mammary epithelium

Electroluminescence in polymer-fullerene photovoltaic cells

We report electroluminescence (EL) in photovoltaic (PV) cells based on semiconducting polymer-fullerene composites. By applying a forward bias to the PV cells, the devices exhibited a clear EL action with a peak around 1.5 eV. We ascribe this peak to an "electric field-assisted exciplex" formed between the electrons in the fullerenes and the holes in the polymers, thereby resulting in radiative recombination in the composites. This finding is totally unexpected because of a strong photoluminescence quenching in the same materials. Since the same devices also showed typical photovoltaic effects under illumination, our results demonstrate a dual functionality in one device; polymer photovoltaic cells and polymer light-emitting diodes.open464

Glioblastoma-derived spheroid cultures as an experimental model for analysis of EGFR anomalies

Glioblastoma cell cultures in vitro are frequently used for investigations on the biology of tumors or new therapeutic approaches. Recent reports have emphasized the importance of cell culture type for maintenance of tumor original features. Nevertheless, the ability of GBM cells to preserve EGFR overdosage in vitro remains controversial. Our experimental approach was based on quantitative analysis of EGFR gene dosage in vitro both at DNA and mRNA level. Real-time PCR data were verified with a FISH method allowing for a distinction between EGFR amplification and polysomy 7. We demonstrated that EGFR amplification accompanied by EGFRwt overexpression was maintained in spheroids, but these phenomena were gradually lost in adherent culture. We noticed a rapid decrease of EGFR overdosage already at the initial stage of cell culture establishment. In contrast to EGFR amplification, the maintenance of polysomy 7 resulted in EGFR locus gain and stabilization even in long-term adherent culture in serum presence. Surprisingly, the EGFRwt expression pattern did not reflect the latter phenomenon and we observed no overexpression of the tested gene. Moreover, quantitative analysis demonstrated that expression of the truncated variant of receptor—EGFRvIII was preserved in GBM-derived spheroids at a level comparable to the initial tumor tissue. Our findings are especially important in the light of research using glioblastoma culture as the experimental model for testing novel EGFR-targeted therapeutics in vitro, with special emphasis on the most common mutated form of receptor—EGFRvIII

Photoinduced electron transfer from π-conjugated polymers onto Buckminsterfullerene, fulleroids, and methanofullerenes

We present near-steady-state photoinduced absorption (PIA), photoluminescence, and light-induced electron spin resonance (LESR) studies on photoinduced electron transfer reactions from poly(bis-2,5-epi-cholestanoxy-1,4-phenylene vinylene) (BeCHA-PPV) as a donor to Buckminsterfullerene (C60) and a number of functionalized fullerenes as acceptors. We show that functionalized fullerenes with a solubilizing side chain linked to C60 in a [5,6] (fulleroid) or [6,6] (methanofullerene) fashion, are efficient electron acceptors towards BeCHA-PPV, as evidenced from changes in the PIA, the efficient quenching of the photoluminescence, and the LESR spectra of BeCHA-PPV cation and fullerene anion radicals. The increased miscibility of the functionalized fullerenes with the conjugated polymer as compared to C60, can be important for the preparation of future electrooptic devices, based on the photoinduced charge separation.

The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A

The immunosuppressive action of the calcineurin inhibitor cyclosporine A (CsA) stems from the inhibition of nuclear factor of activated T cells (NFAT) signaling in T cells. CsA is also used for the treatment of proteinuric kidney diseases. As it stands, the antiproteinuric effect of CsA is attributed to its immunosuppressive action. Here we show that the beneficial effect of CsA on proteinuria is not dependent on NFAT inhibition in T cells, but rather results from the stabilization of the actin cytoskeleton in kidney podocytes. CsA blocks the calcineurin-mediated dephosphorylation of synaptopodin, a regulator of Rho GTPases in podocytes, thereby preserving the phosphorylation-dependent synaptopodin–14-3-3β interaction. Preservation of this interaction, in turn, protects synaptopodin from cathepsin L–mediated degradation. These results represent a new view of calcineurin signaling and shed further light on the treatment of proteinuric kidney diseases. Novel calcineurin substrates such as synaptopodin may provide promising starting points for antiproteinuric drugs that avoid the serious side effects of long-term CsA treatment

Carbon and Nitrogen Isotope Effects Associated with the Dioxygenation of Aniline and Diphenylamine

Dioxygenation of aromatic rings is frequently the initial step of biodegradation of organic subsurface pollutants. This process can be tracked by compound-specific isotope analysis to assess the extent of contaminant transformation, but the corresponding isotope effects, especially for dioxygenation of N-substituted, aromatic contaminants, are not well understood. We investigated the C and N isotope fractionation associated with the biodegradation of aniline and diphenylamine using pure cultures of <i>Burkholderia</i> sp. strain JS667, which can biodegrade both compounds, each by a distinct dioxygenase enzyme. For diphenylamine, the C and N isotope enrichment was normal with ε_C- and ε_N-values of −0.6 ± 0.1‰ and −1.0 ± 0.1‰, respectively. In contrast, N isotopes of aniline were subject to substantial inverse fractionation (ε_N of +13 ± 0.5‰), whereas the ε_C-value was identical to that of diphenylamine. A comparison of the apparent kinetic isotope effects for aniline and diphenylamine dioxygenation with those from abiotic oxidation by manganese oxide (MnO₂) suggest that the oxidation of a diarylamine system leads to distinct C–N bonding changes compared to aniline regardless of reaction mechanism and oxidant involved. Combined evaluation of the C and N isotope signatures of the contaminants reveals characteristic Δδ¹⁵N/Δδ¹³C-trends for the identification of diphenylamine and aniline oxidation in contaminated subsurfaces and for the distinction of aniline oxidation from its formation by microbial and/or abiotic reduction of nitrobenzene