Treatment of esophageal tumors using high intensity intraluminal ultrasound: first clinical results

<p>Abstract</p> <p>Background</p> <p>Esophageal tumors generally bear a poor prognosis. Radical surgery is generally the only curative method available but is not feasible in the majority of patients; palliative therapy with stent placement is generally performed. It has been demonstrated that High Intensity Ultrasound can induce rapid, complete and well-defined coagulation necrosis. Thus, for the treatment of esophageal tumors, we have designed an ultrasound applicator that uses an intraluminal approach to fill up this therapeutic gap.</p> <p>Methods</p> <p>Thermal ablation is performed with water-cooled ultrasound transducers operating at a frequency of 10 MHz. Single lesions extend from the transducer surface up to 10 mm in depth when applying an intensity of 14 W/cm²for 10s. A lumen inside the therapy applicator provides path for an endoscopic ultrasound imaging probe operating at a frequency of 12 MHz. The mechanical rotation of the applicator around its axis enables treatment of sectorial or cylindrical volumes. This method is thus particularly suitable for esophageal tumors that may develop only on a portion of the esophageal circumference. Previous experiments were conducted from bench to <it>in vivo </it>studies on pig esophagi.</p> <p>Results</p> <p>Here we report clinical results obtained on four patients included in a pilot study. The treatment of esophageal tumors was performed under fluoroscopic guidance and ultrasound imaging. Objective tumor response was obtained in all cases and a complete necrosis of a tumor was obtained in one case. All patients recovered uneventfully and dysphagia improved significantly within 15 days, allowing for resuming a solid diet in three cases.</p> <p>Conclusion</p> <p>This clinical work demonstrated the efficacy of intraluminal high intensity ultrasound therapy for local tumor destruction in the esophagus.</p

Uncovering a Macrophage Transcriptional Program by Integrating Evidence from Motif Scanning and Expression Dynamics

Macrophages are versatile immune cells that can detect a variety of pathogen-associated molecular patterns through their Toll-like receptors (TLRs). In response to microbial challenge, the TLR-stimulated macrophage undergoes an activation program controlled by a dynamically inducible transcriptional regulatory network. Mapping a complex mammalian transcriptional network poses significant challenges and requires the integration of multiple experimental data types. In this work, we inferred a transcriptional network underlying TLR-stimulated murine macrophage activation. Microarray-based expression profiling and transcription factor binding site motif scanning were used to infer a network of associations between transcription factor genes and clusters of co-expressed target genes. The time-lagged correlation was used to analyze temporal expression data in order to identify potential causal influences in the network. A novel statistical test was developed to assess the significance of the time-lagged correlation. Several associations in the resulting inferred network were validated using targeted ChIP-on-chip experiments. The network incorporates known regulators and gives insight into the transcriptional control of macrophage activation. Our analysis identified a novel regulator (TGIF1) that may have a role in macrophage activation

The anti-bacterial iron-restriction defence mechanisms of egg white; the potential role of three lipocalin-like proteins in resistance against Salmonella

Salmonella enterica serovar Enteritidis (SE) is the most frequently-detected Salmonella in foodborne outbreaks in the European Union. Among such outbreaks, egg and egg products were identified as the most common vehicles of infection. Possibly, the major antibacterial property of egg white is iron restriction, which results from the presence of the iron-binding protein, ovotransferrin. To circumvent iron restriction, SE synthesise catecholate siderophores (i.e. enterobactin and salmochelin) that can chelate iron from host iron-binding proteins. Here, we highlight the role of lipocalin-like proteins found in egg white that could enhance egg-white iron restriction through sequestration of certain siderophores, including enterobactin. Indeed, it is now apparent that the egg-white lipocalin, Ex-FABP, can inhibit bacterial growth via its siderophore-binding capacity in vitro. However, it remains unclear whether ex-FABP performs such a function in egg white or during bird infection. Regarding the two other lipocalins of egg white (Cal-γ and α-1-glycoprotein), there is currently no evidence to indicate that they sequester siderophores

Metamorphosis of Subarachnoid Hemorrhage Research: from Delayed Vasospasm to Early Brain Injury

Delayed vasospasm that develops 3–7 days after aneurysmal subarachnoid hemorrhage (SAH) has traditionally been considered the most important determinant of delayed ischemic injury and poor outcome. Consequently, most therapies against delayed ischemic injury are directed towards reducing the incidence of vasospasm. The clinical trials based on this strategy, however, have so far claimed limited success; the incidence of vasospasm is reduced without reduction in delayed ischemic injury or improvement in the long-term outcome. This fact has shifted research interest to the early brain injury (first 72 h) evoked by SAH. In recent years, several pathological mechanisms that activate within minutes after the initial bleed and lead to early brain injury are identified. In addition, it is found that many of these mechanisms evolve with time and participate in the pathogenesis of delayed ischemic injury and poor outcome. Therefore, a therapy or therapies focused on these early mechanisms may not only prevent the early brain injury but may also help reduce the intensity of later developing neurological complications. This manuscript reviews the pathological mechanisms of early brain injury after SAH and summarizes the status of current therapies

Present state and future perspectives of using pluripotent stem cells in toxicology research

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed

Interstitial devices for minimally invasive thermal ablation by high-intensity ultrasound.

10 pagesInterstitial ultrasound applicators have been proposed for treating deep-seated tumours that cannot be reached with extra-corporeal high-intensity focused ultrasound. In addition, interstitial ultrasound offers several advantages compared with conventional ablation technology (radiofrequency, microwaves, cryotherapy) in terms of penetration, speed of coagulation, ability to direct and control the thermal lesion and compatibility with image monitoring. The ultrasound source is brought as close as possible to the target in order to minimize the effects of attenuation and phase aberration along the ultrasound pathway. The present paper is a review of the interstitial applicators that were described during the last decade in the literature. It is presented in three sections. The technical aspects common to all applicators are first described. For example, most-described applicators are sideview applicators whose active element is water-cooled and operates at rather high frequency (above 3 MHz) in order to promote heating. Then the different potential techniques for monitoring treatment administered by the interstitial route are presented and illustrated through a review of image-guided interstitial thermal ablation. Three major techniques of imaging are used for guiding interstitial treatment: MRI, ultrasound and fluoroscopy. The third section goes in to further detail on diverse described medical applications