Showing papers by "Markus Meissner published in 2017"

Histone deacetylase inhibitors interfere with angiogenesis by decreasing endothelial VEGFR-2 protein half-life in part via a VE-cadherin-dependent mechanism.

Abstract: Recent evidence suggests that histone deacetylase inhibitors (HDACi) may mediate part of their antitumor effects by interfering with tumor angiogenesis. As signalling via the vascular endothelial growth factor receptor-2 (VEGFR-2) pathway is critical for angiogenic responses during tumor progression, we explored whether established antitumor effects of HDACi are partly mediated through diminished endothelial VEGFR-2 expression. We therefore examined the potential impact of three different HDACi, trichostatin A (TSA), sodium butyrate (But) and valproic acid (VPA), on VEGFR-2 protein expression. TSA, VPA and But significantly inhibit VEGFR-2 protein expression in endothelial cells. Pertinent to these data, VEGFR-2 protein half-life is shown to be decreased in response to HDACi. Recently, it could be demonstrated that expression of VE-cadherin influences VEGFR-2 protein half-life. In our experiments, VEGFR-2 downregulation was accompanied by HDACi-induced VE-cadherin suppression. Interestingly, siRNA-mediated knockdown of VE-cadherin led to a pronounced loss of VEGFR-2 expression on the protein as well as on the mRNA level, implicating that VE-cadherin not only influences VEGFR-2 protein half-life but also the transcriptional level. To further distinguish which of the eight different histone deacetylases are responsible for the regulation of VEGFR-2 expression, specific HDAC genes were silenced by transfecting respective siRNAs. These studies revealed that HDACs 1, 4, 5 and 6 are preferentially involved in VEGFR-2 expression. Therefore, these results provide an explanation for the anti-angiogenic action of HDAC inhibitors via a VE-cadherin, HDAC 1 and HDACs 4-6-mediated suppression of VEGFR-2 expression and might be of importance in the development of new anti-angiogenic drugs.

Magnetic Lenz lenses improve the limit-of-detection in nuclear magnetic resonance

Abstract: A high NMR detection sensitivity is indispensable when dealing with mass and volume-limited samples, or whenever a high spatial resolution is required. The use of miniaturised RF coils is a proven way to increase sensitivity, but situations may arise where space restrictions could prevent the use of a small resonant coil, e.g., in the interior of the smallest practicable micro-coils. We present the use of magnetic lenses, denoted as Lenz lenses due to their working principle, to focus the magnetic flux of an RF coil into a smaller volume and thereby locally enhance the sensitivity of the NMR experiment—at the expense of the total sensitive volume. Besides focusing, such lenses facilitate re-guiding or re-shaping of magnetic fields much like optical lenses do with light beams. For the first time we experimentally demonstrate the use of Lenz lenses in magnetic resonance and provide a compact mathematical description of the working principle. Through simulations we show that optimal arrangements can be found.

Photodynamic Treatment of Oral Squamous Cell Carcinoma Cells with Low Curcumin Concentrations.

Abstract: Objective: Curcumin is known for its anti-oxidative, anti-inflammatory and anti-tumorigenic qualities at concentrations ranging from 3.7µg/ml to 55µg/ml. Therefore it is pre-destined for tumour therapy. Due to high oral doses that have to be administered and the low bioavailability of curcumin new therapy concepts have to be developed. One of these therapy concepts is the combination of low curcumin concentrations and UVA or visible light. Aim of our study was to investigate the influence of this treatment regime on oral squamous cell carcinoma cells. Materials and Methods: A human oral squamous cell carcinoma cell line (HN) was pre-incubated with low curcumin concentrations (0.01µg/ml to 1µg/ml). Thereafter cell cultures were either left un-irradiated or were irradiated either with 1J/cm2 UVA or for 5min with visible light. Quantitative analysis of proliferation, membrane integrity, oxidative potential and DNA fragmentation were done. Results: It could be shown that low curcumin concentrations neither influenced proliferation, nor cell morphology, nor cell integrity nor apoptosis. When combining these curcumin concentrations with UVA or visible light irradiation cell proliferation as well as development of reactive oxygen species was reduced whereas DNA fragmentation was increased. Concentration as well as light entity specific effects could be observed. Conclusions: The present findings substantiate the potential of the combination of low curcumin concentrations and light as a new therapeutic concept to increase the efficacy of curcumin in the treatment of cancer of the oral mucosa.

The erbium:YAG Laser: a new technique for the treatment of scrotal calcinosis.

Abstract: ster of her fourth pregnancy, the patient noticed the recurrence of blisters, followed 1 week later by fetal death. At that time, the level of anti-BP180 was over 200 IU/mL. When the patient consulted in her fifth pregnancy, she was 2 months pregnant. The clinical examination was normal but the blood tests detected a significant titre of anti-BP180 (91 IU/ml) reflecting a high risk of recurrence in a patient who had experienced several PG complications. Because of her medical history, ciclosporine and oral steroids were ruled out and a preventive treatment with rituximab was introduced off-label. The choice of this therapeutic approach was based on the remarkable outcomes achieved in patients treated with rituximab for other autoimmune blistering diseases such as recalcitrant bullous pemphigoid and persistent postpartum PG in a reported case. The patient received two infusions of rituximab 1 g at week 9 and 11. Following this treatment, the immunologic monitoring showed a slight decrease in antibody titres down to 50 IU/mL (Fig 2). There was no recurrence of PG and the patient gave birth to a healthy full-term baby. The follow-up of the mother and child during the 6 months post-partum showed neither clinical nor biological abnormalities, especially no lymphopenia or hypogammaglobulinemia. Even though it is recommended to avoid rituximab during pregnancy due to insufficient data, several reports among which a recent retrospective study performed by the EULAR (European League Against Rheumatism) are in favour of a good maternal and fetal tolerance of rituximab. The main risk seems to be a transient immunosuppression in newborns when the infusion is given after the first trimester. The favourable outcome achieved both in the patient and her baby suggests that rituximab could be an efficient and welltolerated preventive treatment of PG. However, its use should be restricted to selected patients with a history of severe recurrent PG, presenting detectable circulating autoantibodies at the beginning of pregnancy. M. Tourte, F. Brunet-Possenti,* S. Mignot, L. Gavard, V. Descamps Department of Dermatology, Bichat Claude Bernard Hospital, Paris, France, Department of Immunology, Bichat Claude Bernard Hospital, Paris, France, Department of Obstetrics, Louis Mourier Hospital, Paris, France *Correspondence: F. Brunet-Possenti. E-mail: florence.brunet-possenti @aphp.fr

Acting without Central Agent-Considerations for a Self-Model at the Cellular Level.

Abstract: Fossil discoveries suggest that life began on earth about 3.8 billion years ago. At first there were single-celled organisms with no nuclei (prokaryotes), later ∼2.7 billion years ago, protozoa developed which are cells with a nucleus (eukaryotes). Only since about 800 million years have multicellular organisms (eumetazoa) emerged and with that the ability to evolve specialized cells, such as nerve cells. The function of nerve cells is to receive information from both the internal and external environment, interpret and translate it into body reactions e.g., muscle contractions which change the body’s position. In radially symmetric multicellular organisms such as jellyfish, there is a loose network of nerves which condenses in higher organisms with bilateral symmetry to a central nervous system. In bilateria the main axis is mostly in the direction of movement, where, at the front, uptake of nutrients takes place. This defines the starting point for cephalization with the emergence of a cerebral ganglion. Later in evolution, according to the prosomeric model the morphology of the vertebrate forebrain emerges from segmental structures, the number, and interconnections of ganglia increased forming a brain, the place where we assume cognition and intelligence is located. The everyday neuro-fixation ignores indications that already single cells show complex behavior patterns with a kind of basal intelligence and the ability to memorize. How do single cells accomplish this? In the following we hypothesize that cells may have a kind of self-model, a representation of themselves.

Vacuum sealing with a 'flipper' for the treatment of plantar excision defects.

Abstract: The therapeutic mainstay in the treatment of acral lentiginous melanoma is excision with suffi cient surgical margins in order to prevent possible local tumor recurrence [ 1 ] . At the transition between the sole and the toes in particular, primary closure is rarely feasible. In addition to full-thickness and split-thickness grafts, options for defect closure include free fl ap repair. Secondary intention healing may also be considered but is relatively time-consuming. Given the tissue loss involved, the excision defects are frequently too deep to allow for skin grafting to be performed during the same procedure. In this context, vacuum sealing can be used to induce granulation [ 2–4 ] . However, this technique may not be practical if the plantar excision defects extend as far as the metatarsophalangeal joints. Here, achieving adequate airtightness, which is a sine qua non for vacuum therapy, is challenging. Herein, we like to introduce the ‘fl ipper’ vacuum seal as a suitable technique for the hermetic sealing of plantar excision defects.