Sol-gel synthesis of nano-scale, end-member albite feldspar (NaAlSi3O8).

Feldspars are the most abundant minerals in the Earth's crust, and are also important constituents of many lunar rocks and some stony meteorites. Albite (NaAlSi3O8) makes up the sodium corner of the feldspar ternary diagram (KAlSi3O8 - NaAlSi3O8 - CaAl2Si2O8) and connects the alkali-feldspar and plagioclase binary joins. Synthesis of albite, however, has long been a problem, even at high temperatures and even at high pressures when dry. In fact, most successful syntheses require the combination of high-pressure, high-temperature, and hydrothermal environments. This paper presents a sol-gel method of albite synthesis that requires hydrothermal processing followed by high-temperature recrystallization, but no high-pressure environments. This has the advantage of allowing synthesis of relatively large amounts of material and controlled elemental substitutions.

[Preclinical models in head and neck tumors : Evaluation of cellular and molecular resistance mechanisms in the tumor microenvironment]. / Präklinische Modelle für Kopf-Hals-Tumoren : Aufklärung zellulärer und molekularer Resistenzmechanismen im Gewebekontext.

Because head and neck squamous cell carcinomas (HNSCC) are characterized by a distinct intertumorigenic and intratumorigenic heterogeneity, they often show substantial differences in the response to established therapy strategies. At present, a multitude of biologics and new pharmacological compounds for targeted therapies are available that allow more efficient and less toxic treatment. There is increasing pressure to establish predictive assays not only for ex ante analysis of the individual patient response to combined chemoradiotherapy and targeted therapies but also for investigation of the efficacy of new drugs. In this respect it is essential to maintain the pathophysiological tissue composition as it is known that paracrine tumor-stroma cell interactions may influence tumor reactivity to treatment. More complex models for individualized sensitivity testing have recently been described and the results are promising to pave the way for personalized cancer therapy. This review article focuses on different systems for maintaining the tumor microenvironment and hence the individual cellular composition, such as 3D organotypic models, organotypic multicellular spheroids, patient-derived xenografts and ex vivo tissue cultures and discusses the advantages and disadvantages in terms of translation into clinical application.

Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies.

METHOD: The safety of oral sorafenib up to a maximum protocol-specified dose combined with dacarbazine in patients with metastatic, histologically confirmed melanoma was investigated in a phase I dose-escalation study and the activity of the combination was explored in an open-label phase II study. RESULTS: In the phase I study, three patients were treated with sorafenib 200 mg twice daily (b.i.d.) plus 1000 mg m(-2) dacarbazine on day 1 of a 21-day cycle and 15 patients had the sorafenib dose escalated to 400 mg b.i.d. without reaching the maximum tolerated dose of the combination. In the phase II study (n=83), the overall response rate was 12% (95% CI: 6, 21): one complete and nine partial, with median response duration of 46.7 weeks. Stable disease was the best response in 37%; median duration was 13.3 weeks. Median overall survival (OS) was 37.0 weeks (95% CI: 33.9, 46.0). CONCLUSION: Oral sorafenib combined with dacarbazine had acceptable toxicity and some antineoplastic activity against metastatic melanoma.

Comparison of p16(INK4a) expression with p53 alterations in head and neck cancer by tissue microarray analysis.

We investigated whether there is a relationship between loss of p16(INK4a) protein expression and p53 alterations in head and neck squamous cell carcinomas (HNSCCs). For this purpose, immunohistochemistry was performed on tissue microarrays of 664 tumours; this represents the largest HNSCC cohort studied for molecular biomarkers. Loss of p16(INK4a) protein expression was associated with aberrant p53 expression (negative or overexpressed) in the total cohort, and with TP53 mutations in 200 tumours analysed (p < 0.0001 each). Both loss of p16(INK4a) expression and p53 alterations differed significantly across both tumour sites and stages, being more prevalent in the hypopharynx than in the other tumour sites and in advanced tumour stages. As a possible link between p53 status and p16(INK4a) loss, we found that increased DNA methyltransferase 1 protein levels occurred preferentially in tumours with aberrant p53 (p = 0.001) and negative p16(INK4a) expression (p = 0.0004). In the total cohort, there was a borderline significant difference in patient survival across three p16(INK4a) expression levels (negative, positive, high), with loss of p16(INK4a) expression showing shortest survival. It is suggested that loss of p16(INK4a) expression and p53 alterations should be viewed as related events involved in the early carcinogenic process.

Detailed gene expression analysis but not microsatellite marker analysis of 9p21 reveals differential defects in the INK4a gene locus in the majority of head and neck cancers.

The INK4a gene locus on chromosome 9p21 encodes two proteins, p16(INK4a) and p14(ARF), which influence cell cycle control regulated by pRb and p53. The objective of this study was to use different methods for the analysis of the incidence of changes at the INK4a locus in head and neck cancer (HNSCC). Primary tumours were analysed for allelic imbalances (AI) with microsatellite markers for chromosome 9, by immunohistochemistry (IHC) and IHC with enhanced sensitivity by tyramide signal amplification (TSA-IHC), and by RT-PCR. No homozygous deletions at 9p21 were detected. AI at 9p21, which was found in approximately 60% of the tumours, completely failed to indicate the functional inactivation of the two INK4a gene products. Immunostaining of normal squamous epithelia revealed very low levels of p16(INK4a), whereas p14(ARF) was readily detectable. In 160 tumours, IHC suggested a loss of p16(INK4a) expression in 90%. However, by TSA-IHC, only 53.7% showed loss of p16(INK4a) expression, and this was consistent with the RT-PCR analyses. In 100 tumours analysed for both proteins, selective loss of p16(INK4a) occurred in 37%; loss of p14(ARF) was found in only 15%, and selective loss in only 4%; 11% of the tumours had lost both proteins. We conclude that only IHC with high sensitivity and the combined expression analysis of mRNAs and proteins is suitable for studying the role of INK4a in HNSCC. The INK4a gene expression defects are frequent but not universal and primarily affect p16(INK4a). Their clinical impact is still not clear.

[Radiation exposure of teeth and temporomandibular joints by radiography]. / Strahlenbelastung bei Röntgenaufnahmen der Zähne und der Kiefergelenke.

According to a report by Poretti (1975) 21,4% of all medical diagnostic radiographs in Switzerland are dental. In order to determine the associated radiation doses to patients, phantom measurements of skin and gonad exposures were made utilizing modern dental x-ray equipment and techniques. Following procedures in accordance with federal safety regulations it was not possible to measure dose values at the gonad level by single dental or temporomandibular radiographs, even by the most sensitive measuring device. 50 cumulative exposures without lead apron resulted in a range of gonad doses from 3.1 to 199 microR for dental and temporomandibular joint x-rays. Results of skin surface doses ranged from 38 to 289 mR for single dental film exposure and from 64 to 494 mR for single TMJ exposures. Consistent use of parallel technique with long cone equipment, small diaphragms, high kilovoltage and use of the lead apron guarantee great safety against radiation hazard in dental radiography.