High mutation frequency at Ha-ras exons 1-4 in squamous cell carcinomas from PUVA-treated psoriasis patients

Clinical follow-up studies have revealed that PUVA-treated patients are at increased risk of skin cancer, particularly squamous cell carcinoma (SCC). However, since psoralen and UVA (PUVA) is not only a potent mutagen and carcinogen but also an immunosuppressor, and since other (co)carcinogenic factors often exist in psoriasis patients, the exact causes and mechanisms of PUVA-associated SCC are still not completely understood. In order to fill this gap the tools of molecular epidemiology are being used to study the SCC mutational spectra of p53 and Ha-ras, two of the most commonly mutated genes in human cancers. A previous mutation analysis revealed that SCC in PUVA-treated patients often carried mutated p53 genes and that many of the mutations had the UV fingerprint (i.e. C-->T or CC-->TT transitions at dipyrimidine sites). In the present study DNA-sequencing analysis revealed a total of 18 Ha-ras missense or nonsense mutations at exons 1-4 in 13 of 17 SCC (76%) from 8 of 11 (73%) PUVA-treated psoriasis patients. Six of the 18 mutations (33%) were of UV-fingerprint type (C-->T transitions), five (28%) were at 5'-TpG sites (i.e. potential psoralen-binding sites and thus potentially caused by PUVA) and seven were of other type (39%), including six G:C-->T:A transversions at hotspot codon 12. In addition, in the case of 6 of the 11 subjects (55%) both tumor and normal skin samples contained a T:A-->C:G base change at codon 27 (a 5'-ATT site), a change previously hypothesized to be a possible silent Ha-ras polymorphism at one allele. When we compared the present Ha-ras mutation spectrum with the p53 mutation spectrum from a previous study of the samples, we found that approximately half of the tumors harbored mutations in both Ha-ras and p53. Together, our results indicate that Ha-ras mutations are present in a large proportion of PUVA-associated SCC and that UVB, PUVA and other agents may induce Ha-ras mutations and act together with p53 in the formation of SCC in psoriasis patients.     

Magnon contribution to the magnetoresistance of iron nanowires deposited using pulsed electrodeposition

Iron nanowires with a square cross section are grown by pulsed electrodeposition within a newly developed nanochannel template that allows for easy characterization. Measurements of the magnetoresistance as a function of magnetic field and temperature are performed within a large parameter window allowing for the investigation of the magnonic contribution to the magnetoresistance of electrodeposited iron nanowires. Values for the temperature dependent magnon stiffness D (T) are extracted: D (T) = D₀(1 – d₁T²) = 365(1 – 4.4 × 10^–6 · T² · K^–2) meV Ų.

     

Dual-detector-post-column reactor system for the detection of isoenzymes separated by high-performance liquid chromatography. I. Description and theory

We describe a dual-detector-post-column chromatographic reaction detector system that corrects for substances present in biological samples that interfere with the measurement of isoenzymes separated on a chromatographic column. The response observed at the detector in front of the reaction coil is mathematically dispersed, time transformed and subtracted from the detector behind the coil to produce a blank corrected chromatogram. The same computer program calculates peak areas and other chromatographic parameters such as height equivalent to a theoretical plate and retention time. In addition, we have evaluated the dispersion effects caused by various changes in our experimental system.     

In Vitro Studies of Fe3O4-ZIF-8 Core–Shell Nanoparticles Designed as Potential Theragnostics

Theragnostics represent a combination of therapy and diagnosis within one system. Herein, Fe₃O₄-ZIF-8 core–shell nanoparticles are developed and suggested as candidates for theragnostic applications in cancer treatment. A drug loaded metal–organic framework ZIF-8 (zeolitic imidazolate framework-8) represents the therapeutic tool, while the Fe₃O₄ core is included to enable the material visualization by magnetic resonance imaging (MRI). A reliable synthesis of Fe₃O₄-ZIF-8 core–shell nanoparticles of an average size below 100 nm is reported. The nanoparticles are characterized by FT-IR, TGA, XRPD, TEM, STEM-EDS, DLS, ICP-OES, CHN-elemental analysis, SQUID measurements, and MRI. Moreover, their chemical stability and in vitro cytotoxicity against fibroblast and selected cancer cell lines are evaluated. As a model drug, arsenic trioxide—a promising anticancer drug—is used. The drug release can be triggered by a pH change from 7.4 to 6.0 and the nanoparticles can be visualized by MRI in vitro, thus a potential theragnostic agent for cancer treatment is developed.     

Zeolitic Imidazolate Framework-8 as pH-Sensitive Nanocarrier for “Arsenic Trioxide” Drug Delivery

Previous results revealed that arsenic trioxide might be used as promising therapeutic agent for the treatment of some solid tumours as atypical teratoid rhabdoid tumours (ATRT). However, in order to become an approved drug for solid tumour treatment, the active formulation has to get more efficient and feasible—but at the same time less toxic. One of the possibilities to achieve this dichotomy is to use nanomedicine tools. Herein, we report on the Zn-based metal–organic framework ZIF-8 (Zeolitic Imidazolate Framework-8) which turned out to be a promising candidate for the delivery of As^III species. It conjointly features a high drug loading capacity and a prominent pH-triggered release behaviour. As^III-loaded ZIF-8 nanoparticles coated and non-coated with polyethylene glycol were studied by XRPD, IR, Raman, TGA, TEM, EDX, CHN-elemental analysis, sorption analysis and ICP-OES, and their cytotoxicity was evaluated in vitro.     

Influence of Nanoparticle Processing on the Thermoelectric Properties of (BixSb1−X)2Te3 Ternary Alloys

The synthesis of phase-pure ternary solutions of tetradymite-type materials (Bi_xSb_1−x)₂Te₃ (x=0.25; 0.50; 0.75) in an ionic liquid approach has been carried out. The nanoparticles are characterized by means of energy-dispersive X-ray spectroscopy (EDX), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), and transmission electron microscopy. In addition, the role of different processing approaches on the thermoelectric properties - Seebeck coefficient as well as electrical and thermal conductivity - is demonstrated.     

A novel synthesis of ultrathin CoPt3 nanowires by dealloying larger diameter Co99Pt1 nanowires and subsequent stress-induced crack propagation

A novel approach to the fabrication of ultrathin CoPt₃ nanowires with a diameter of a few nanometers has been developed, by taking advantage of the volume shrinkage and formation of nanoporous structures upon dealloying electrodeposited Co₉₉Pt₁ nanowires (28 nm in diameter), followed by an ultrasonication treatment. The as-produced ultrathin CoPt₃ nanowires have an average diameter of 5 nm and lengths of up to 10 μm, and are found to be ferromagnetic at room temperature.