Important role of Nfkb2 in the Kras-driven carcinogenesis in the pancreas.

Background: Oncogenic Kras initiates and drives carcinogenesis in the pancreas by complex signaling networks, including activation of the NFκB pathway. Although recent evidence has shown that oncogenic gains in Nfκb2 collaborate with Kras in the carcinogenesis, no data at the level of genetics for the contribution of Nfκb2 is available so far.

Methods: We used Nfkb2 knock-out mice to decipher the role of the gene in Kras-driven carcinogenesis in vivo.

Toxic effects and biodistribution of ultrasmall gold nanoparticles.

Gold nanoparticles (AuNPs) have been extensively explored in biomedical applications, for example as drug carriers, contrast agents, or therapeutics. However, AuNP can exhibit cytotoxic profile, when the size is below 2 nm (ultrasmall AuNP; usAuNP) and when the stabilizing ligands allow for access to the gold surface either for the direct interaction with biomolecules or for catalytic activity of the unshielded gold surface. Furthermore, usAuNP exhibits significantly different biodistribution and enhanced circulation times compared to larger AuNP.

Wide Band-Gap Bismuth-based p-Dopants for Opto-Electronic Applications.

Ten new efficient p-dopants for conductivity doping of organic semiconductors for OLEDs are identified. The key advantage of the electrophilic tris(carboxylato) bismuth(III) compounds is the unique low absorption of the resulting doped layers which promotes the efficiency of OLED devices. The combination of these features with their low fabrication cost, volatility, and stability, make these materials very attractive as dopants in organic electronics.

MYC and EGR1 synergize to trigger tumor cell death by controlling NOXA and BIM transcription upon treatment with the proteasome inhibitor bortezomib.

The c-MYC (MYC afterward) oncogene is well known for driving numerous oncogenic programs. However, MYC can also induce apoptosis and this function of MYC warrants further clarification. We report here that a clinically relevant proteasome inhibitor significantly increases MYC protein levels and that endogenous MYC is necessary for the induction of apoptosis.

Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat.

Background: There is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers. We hypothesized that gold (Au) NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. transcellular transport across the hemochorial placenta, 2.

Acetylation as a transcriptional control mechanism-HDACs and HATs in pancreatic ductal adenocarcinoma.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors with a dismal prognosis. Although our understanding of the carcinogenesis of the disease increases continuously, no effective conservative therapeutic strategies exist. Therefore, novel targets have to be defined at the experimental level.

Targeting histone deacetylases in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease with a median survival below 6 months and a 5-year survival rate below 1%. Effective therapies for locally advanced or metastatic tumours are missing and curatively resected patients relapse in over 80% of the cases. Although histone deacetylases (HDACs) are involved in the control of proliferation, apoptosis, differentiation, migration and angiogenesis of cancer cells, knowledge about the expression patterns and functions of individual HDAC isoenzymes in pancreatic cancer is sparse.

The human lung cell line A549 does not develop adaptive protection against the DNA-damaging action of formaldehyde.

The alkaline comet assay was used to further characterize the induction of DNA-protein crosslinks (DPX) by formaldehyde (FA) and their removal in the human lung cell line A549. DPX were indirectly measured as the reduction of gamma ray-induced DNA migration. Repeated treatments of A549 cells with low FA concentrations (up to 100 microM) did not lead to significant differences in the induction of DPX in comparison with a single treatment.

Inhalation of formaldehyde does not induce systemic genotoxic effects in rats.

Male Fischer-344 rats were exposed to formaldehyde (FA) by inhalation for 4 weeks (6 h/day, 5 days/week). Groups of six rats each were exposed to the target concentrations of 0, 0.5, 1, 2, 6, 10 and 15 ppm.

Reproductive cycle-dependent plasticity of perception of acoustic meaning in mice.

How may perception, maternal motivation and behavior of female mammals change during different phases of their estrous cycle? Here, we show effects of estrous cycle phase on the perception of acoustic meaning and maternal behavior in virgin house mice (Mus musculus) during contact with young for which they were co-caring together with the mother. Cycling females in diestrus, proestrus, estrus or metestrus responded to mouse pup wriggling calls and two synthesized call models when they were in a "nursing" position on the pups. Independent of the phase of their estrous cycle, the virgin females' response rates to naturally vocalized calls and the rates of their spontaneous maternal behavior were about half of those of mothers in the same behavioral setting.

The relevance of shape and size of Au55 clusters.

This critical review deals with the history of Au55(PPh3)12Cl6 and its derivatives from the very beginning in 1981 to date. Au55 clusters obtain their special interest from their ultimate size and their ideal cuboctahedral structure. They are part of the family of so-called full-shell clusters, particles with perfectly completed geometries, also represented by icosahedral Au13 clusters.

Molecular biology of pancreatic cancer--new aspects and targets.

Pancreatic ductal adenocarcinoma is a dismal disease with a median survival of less than 6 months and an overall 5-year survival rate less than 1%. This bad prognosis is due to early lymphatic and hematogenic dissemination. Effective therapies for locally advanced or metastatic tumors are very limited and curatively resected patients experience relapse in over 80% of cases.

Genotoxic effects of formaldehyde in the human lung cell line A549 and in primary human nasal epithelial cells.

The alkaline comet assay was used to further characterize the induction of DNA-protein crosslinks (DPX) by formaldehyde (FA) and their removal in the human lung cell line A549 and in primary human nasal epithelial cells (HNEC). DPX were indirectly measured as the reduction of gamma ray-induced DNA migration. FA induced DPX in A549 cells in a concentration-related manner in the range of 100-300 microM.

The genotoxic potential of glutaraldehyde in mammalian cells in vitro in comparison with formaldehyde.

Glutaraldehyde (GA) induces DNA-protein crosslinks (DPX), but conflicting results have been reported with regard to other genotoxic and mutagenic effects in mammalian cells in vitro. We, therefore, characterized the genotoxic and mutagenic potential of GA in V79 cells. Using the alkaline comet assay we demonstrated the induction of DPX by GA (reduction of gamma ray-induced DNA migration) at a concentration of 10 microM and above.

Characterization of the genotoxic potential of formaldehyde in V79 cells.

Formaldehyde (FA) is known to be genotoxic and mutagenic in proliferating mammalian cells in vitro. The present study was performed to further characterize its genotoxic potential in the V79 Chinese hamster cell line. The induction of DNA strand breaks and DNA-protein cross-links (DPXs) was measured by the comet assay in relationship to the induction of sister chromatid exchanges (SCEs) and micronuclei (MN).

HDAC3 is linked to cell cycle machinery in MiaPaCa2 cells by regulating transcription of skp2.

Objective: Histone deacetylases (HDACs) have been linked to cell cycle control in various models, involving regulation of the cyclin-dependent kinase inhibitor p27(Kip1).

Results: Here, we demonstrate that HDAC inhibition by trichostatin A reduces S-phase kinase-associated protein 2 mRNA and protein abundance. Furthermore, in contrast to HDAC1, recruited to the skp2 promoter in the G(0) phase, HDAC3 is bound in early S phase.

Assessment of local genotoxic effects of formaldehyde in humans measured by the micronucleus test with exfoliated buccal mucosa cells.

Volunteers (10 women, 11 men) were exposed to formaldehyde (FA) vapors for 4h per day over a period of 10 working days under strictly controlled conditions. Exposure varied randomly each day from constant 0.15 ppm up to 0.

Local genotoxic effects of formaldehyde in humans measured by the micronucleus test with exfoliated epithelial cells.

Formaldehyde (FA) is genotoxic in vitro in cultured mammalian cells. When FA reaches the nuclear DNA, it forms DNA-protein cross-links (DPX). Incomplete repair of DPX can lead to the formation of mutations, in particular chromosome mutations and micronuclei (MN) in proliferating cells.

Gold nanoparticles: assembly and electrical properties in 1-3 dimensions.

Ligand stabilized gold nanoparticles have attracted much attention in the search for new chemically designed compounds for a future information technology, based on single-electron devices. This article gives an overview about the strategies used to synthesize and to assemble uniform gold nanoparticles in different dimensions as well as about the present status of the electrical properties of these. Examples are given for three-dimensional organisations, for the formation of self-assembled monolayers as well as for one-dimensional assemblies.

Genetic alterations in pancreatic carcinoma.

Cancer of the exocrine pancreas represents the fifth leading cause of cancer death in the Western population with an average survival after diagnosis of 3 to 6 months and a five-year survival rate under 5%. Our understanding of the molecular carcinogenesis has improved in the last few years due to the development of novel molecular biological techniques. Pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells.

Naked Au55 clusters: dramatic effect of a thiol-terminated dendrimer.

Reaction of the thiol-terminated fourth-generation dendrimer 2-G4 (96 SH groups) with the gold cluster compound Au55(PPh3)12Cl6 in a 3:1 molar ratio in dichloromethane results in the formation of bare Au55 clusters. The cuboctahedrally shaped Au55 particles coalesce to well-formed microcrystals (Au55) infinity. The role of the dendrimer is not only to remove the phosphine and chlorine ligands but also to act as an ideal matrix for perfect crystal growth.