There is an ongoing need to do more with less and provide highly multiplexed analysis from limited sample volumes. Improved "sample sparing" assays would have a broad impact across pediatric and other rare sample type studies in addition to enabling sequential sampling. This capability would advance both clinical and basic research applications.
View Article and Find Full Text PDFBackground: Prostatic cancers include a diverse microenvironment of tumor cells, cancer-associated fibroblasts, and immune components. This tumor microenvironment (TME) is a known driving force of tumor survival after treatment, but the standard-of-care tissue freezing or fixation in pathology practice limit the use of available approaches/tools to study the TME's functionality in tumor resistance. Thus, there is a need for approaches that satisfy both clinical and laboratory endpoints for TME study.
View Article and Find Full Text PDFIntercellular signaling drives human development, but there is a paucity of in vitro models that recapitulate important tissue architecture while remaining operationally simple and scalable. As an example, formation of the upper lip and palate requires the orchestrated proliferation and fusion of embryonic facial growth centers and is dependent on paracrine epithelial-mesenchymal signaling through multiple pathways including the Sonic Hedgehog (SHH), transforming growth factor-beta (Tgf-β), bone morphogenic protein (BMP), and epidermal growth factor (EGF) pathways. We have developed a robust, throughput-compatible microphysiological system to model intercellular signaling including epithelial-mesenchymal interactions that is useful for studying both normal and abnormal orofacial development.
View Article and Find Full Text PDFParacrine signaling in the tissue microenvironment is a central mediator of morphogenesis, and modeling this dynamic intercellular activity is critical to understanding normal and abnormal development. For example, Sonic Hedgehog (Shh) signaling is a conserved mechanism involved in multiple developmental processes and strongly linked to human birth defects including orofacial clefts of the lip and palate. SHH ligand produced, processed, and secreted from the epithelial ectoderm is shuttled through the extracellular matrix where it binds mesenchymal receptors, establishing a gradient of transcriptional response that drives orofacial morphogenesis.
View Article and Find Full Text PDFSolid tumors generate a suppressive environment that imposes an overwhelming burden on the immune system. Nutrient depletion, waste product accumulation, hypoxia, and pH acidification severely compromise the capacity of effector immune cells such as T and natural killer (NK) cells to destroy cancer cells. However, the specific molecular mechanisms driving immune suppression, as well as the capacity of immune cells to adapt to the suppressive environment, are not completely understood.
View Article and Find Full Text PDFCellular heterogeneity within the tissue microenvironment may underlie chemotherapeutic resistance and response, enabling tumor evolution; however, this heterogeneity it is difficult to characterize. Here, we present a new approach-pathology-guided micropunching (PGM)-that enables identification and characterization of heterogeneous foci identified in viable human and animal model tissue slices. This technique consists of live-cell tissue labeling using fluorescent antibodies/small molecules to identify heterogeneous foci (e.
View Article and Find Full Text PDFObjective: To determine the role of the aryl hydrocarbon receptor (AHR) in colitis-associated colorectal tumorigenesis.
Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in United States. Chronic intestinal inflammation increases the risk for the development of CRC.
The polyphenolic flavone chrysin has been evaluated as a natural chemopreventive agent due to its anti-cancer effects in a variety of cancer cell lines. However, the mechanism of the chemopreventive effect has been not well established, especially in human colorectal cancer cells. We evaluated the chemopreventive effect of chrysin in three different human colorectal cancer cell lines.
View Article and Find Full Text PDFBackground And Objectives: The incidence of infectious complications associated with continuous regional anesthesia techniques is a matter of concern. Our objective was to determine whether patients suffering from diabetes are at an increased risk of catheter-related infectious complications.
Methods: The German Network for Regional Anaesthesia database was analyzed between 2007 and 2012.
The various measures used to treat the symptoms of Duchenne muscular dystrophy (DMD), i.e. medication with steroids, early operation on contractures and spine deformities as well as cardiac diagnostics and therapy, should always be accompanied by careful monitoring of the patient's respiratory status.
View Article and Find Full Text PDFBackground: In early-stage rectal cancer, the surgeon must decide between the high morbidity of radical surgery and the high recurrence rates of local excision. A prognostic marker could improve patient selection and lower recurrence rates. Micro-ribonucleic acids (miRNAs), small RNAs that often inhibit tumor suppressors, have shown prognostic potential in colorectal cancer.
View Article and Find Full Text PDFIn a prospective controlled trial to compare conventional interscalene brachial plexus block (ISBPB) using anatomic landmarks and electro-stimulation with a combined technique of ultrasound guidance followed by nerve stimulation, 60 patients were randomized into 2 matched equal groups: Group A using nerve stimulation (NS) alone and Group B using the combination of ultrasound and NS. The time to detect the plexus (3.9 ± 4 min in Group A and 3.
View Article and Find Full Text PDFIntroduction: ZM336372 is small molecule tyrosine kinase modulator. It has been shown to inhibit glycogen synthase kinase-3beta (GSK-3beta) through phosphorylation of GSK-3beta at Ser 9. GSK-3beta has previously been shown to mediate cell survival in pancreatic cancer cells.
View Article and Find Full Text PDFAnasthesiol Intensivmed Notfallmed Schmerzther
November 2009
Regional anaesthesia generally is considered to be safe. However, reports of complications with different severities are also well known. The scientific working group of regional anaesthesia of the DGAI has founded a network in conjunction with the BDA.
View Article and Find Full Text PDFBackground: Intraoperative washed autologous transfusion of the scavenged blood can reduce the deterioration of anemia, even during the operation with a comparatively large blood loss. On the other hand, plasma level can not be collected by this system. The preoperative donation and perioperative retransfusion of autologous plasma may reduce the plasma dilution.
View Article and Find Full Text PDFPurpose: This phase I trial sought to define the toxicity, maximally tolerated dose (MTD) and pharmacodynamics of a combination of bortezomib and doxorubicin in patients with advanced malignancies.
Patients And Methods: Twenty-six patients were treated with bortezomib intravenously on days 1, 4, 8 and 11, with doxorubicin also administered intravenously on days 1 and 8, both in a 21-day cycle. Dosing ranged from 1.
Hepatocellular carcinoma has been described to exhibit characteristics similar to that of neuroendocrine tumors (NETs). This includes similar anti-neoplastic responses to extracellular signal-regulated kinase (ERK) activation. NET cells and HepG2 cells have both shown growth inhibition with ERK activation.
View Article and Find Full Text PDFThe metal chelator Triapine, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, is a potent inhibitor of ribonucleotide reductase. EPR spectra consistent with signals from Fe-transferrin, heme, and low-spin iron or cupric ion were observed in peripheral blood mononuclear cells (PBMCs) obtained from patients treated with Triapine. One signal that is unequivocally identified is the signal for Fe-transferrin.
View Article and Find Full Text PDFIntroduction: Atlantoaxial instabilities, which require surgical fixation follow a variety of clinical disorders. Different surgical procedures are used for stabilization of the atlantoaxial complex, mainly posterior wiring techniques and transarticular screw fixation. Nowadays, often a combination of transarticular screws and a posterior one-point fixation is used to achieve a three-point fixation, with superior biomechanical stability and good clinical results.
View Article and Find Full Text PDFDifferent methods to reduce blood loss during spinal surgery have been described already. Although the use of the harmonic scalpel (HS), an ultrasonically activated coagulator, has been described in endoscopic spinal surgery, its efficacy in posterior instrumentation of the spine remains unclear. The aim of this study was to determine if blood loss was lower using the HS than electrocauterization (EC) and to evaluate the cost effectiveness of the HS in reducing the need for transfusion in patients undergoing posterior instrumentation of the spine.
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