The Use of Sunitinib as Maintenance Therapy in a Pediatric Patient With a Poorly Differentiated Thymic Carcinoma.

BACKGROUND: Thymic carcinomas are rare aggressive mediastinal tumors with a median survival of 2 years. OBSERVATION: We present a pediatric patient who was diagnosed with metastatic thymic carcinoma and showed continuous improvement of his primary mass and lung metastases with a regimen of cisplatin/docetaxel followed by long-term maintenance therapy with sunitinib for over 5 years. CONCLUSIONS: This report demonstrates a long-term positive treatment effect using chemotherapy followed by sunitinib in an advanced thymic carcinoma. We are not aware of other reports of pediatric patients with metastatic thymic carcinoma treated with sunitinib maintenance who maintained a durable response for this prolonged period of time.

An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feed Forward Loop Interactions.

Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodeling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory "dimensions" coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Comparative analyses of expression changes subsequent to depletion of Esrrb or Nanog, indicated that a system of interlocked feed-forward loops involving both factors, plays a central part in regulating the timing of mESC fate decisions. Taken together, our meta-analyses support a hierarchical model in which pluripotency is maintained by an Oct4-Sox2 regulatory module, while the timing of differentiation is regulated by a Nanog-Esrrb module.

Mimics of malrotation on pediatric upper gastrointestinal series: a pictorial review.

Intestinal malrotation is a continuum of congenital anomalies due to lack of rotation or incomplete rotation of the fetal intestine around the superior mesenteric artery axis. The abnormal bowel fixation (by mesenteric bands) or absence of fixation of portions of the bowel increases the risk of bowel obstruction, acute or chronic volvulus, and bowel necrosis. The clinical presentation of patients with malrotation without, with intermittent, or with chronic volvulus can be problematic, with an important minority presenting late or having atypical or chronic symptoms, such as intermittent vomiting, abdominal pain, duodenal obstruction, or failure to thrive. The diagnosis is heavily reliant on imaging. Upper GI series remain the gold standard with the normal position of the duodenojejunal junction lateral to the left-sided pedicles of the vertebral body, at the level of the duodenal bulb on frontal views and posterior (retroperitoneal) on lateral views. However, a variety of conditions might influence the position of the duodenojejunal junction, potentially leading to a misdiagnosis of malrotation. Such conditions include improper technique, gastric over distension, splenomegaly, renal or retroperitoneal tumors, liver transplant, small bowel obstruction, the presence of properly or malpositioned enteric tubes, and scoliosis. All of these may cause the duodenojejunal junction to be displaced. We present a series of cases highlighting conditions that mimic malrotation without volvulus to increase the practicing radiologist awareness and help minimize interpretation errors.

Effects of varying serum glucose levels on 18F-FDG biodistribution.

OBJECTIVE: Hyperglycemia has been shown to influence fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake in tumor cells. Therefore, patients are instructed to fast for 6 h, while maintaining serum glucose levels at an acceptable range. The study was performed to evaluate the effect of fasting blood glucose levels on the biodistribution of (18)F-FDG in various tissues including the liver, heart, bone marrow, skeletal muscle, and tumors. MATERIALS AND METHODS: Fingerstick fasting blood glucose is routinely measured on the morning of the procedure. The maximum standardized uptake value (SUV(max)) in the right and left hepatic lobes, left ventricle, sacrum, thigh, and tumor was measured in 229 consecutive patients undergoing (18)F-FDG PET/computed tomography for tumor. Patients were divided into three groups depending on their serum glucose levels: low (<100; n = 53), medium (100-160; n = 149), and high (160-201; n = 27). A retrospective analysis of the relationship between glucose levels and standardized uptake value was performed. RESULTS: There was a statistically significant increase in the average SUV(max) in the right and left hepatic lobes as glucose levels increased (right lobe P=0.00144; left lobe P = 0.03889). Subsequently, pairwise analysis was performed, revealing a statistically significant increase in SUV(max) in the right hepatic lobe between low-glucose and medium-glucose groups and in both hepatic lobes between low and high groups (P < 0.017). No significant difference was observed in any of the other measured tissues. CONCLUSION: This study shows a directly proportional relationship between blood glucose levels and nonpathologic (18)F-FDG biodistribution in the right and left hepatic lobes. The influence of blood glucose on expected biodistribution patterns, particularly in the liver, should be considered during interpretation.

Sig2BioPAX: Java tool for converting flat files to BioPAX Level 3 format.

BACKGROUND: The World Wide Web plays a critical role in enabling molecular, cell, systems and computational biologists to exchange, search, visualize, integrate, and analyze experimental data. Such efforts can be further enhanced through the development of semantic web concepts. The semantic web idea is to enable machines to understand data through the development of protocol free data exchange formats such as Resource Description Framework (RDF) and the Web Ontology Language (OWL). These standards provide formal descriptors of objects, object properties and their relationships within a specific knowledge domain. However, the overhead of converting datasets typically stored in data tables such as Excel, text or PDF into RDF or OWL formats is not trivial for non-specialists and as such produces a barrier to seamless data exchange between researchers, databases and analysis tools. This problem is particularly of importance in the field of network systems biology where biochemical interactions between genes and their protein products are abstracted to networks. RESULTS: For the purpose of converting biochemical interactions into the BioPAX format, which is the leading standard developed by the computational systems biology community, we developed an open-source command line tool that takes as input tabular data describing different types of molecular biochemical interactions. The tool converts such interactions into the BioPAX level 3 OWL format. We used the tool to convert several existing and new mammalian networks of protein interactions, signalling pathways, and transcriptional regulatory networks into BioPAX. Some of these networks were deposited into PathwayCommons, a repository for consolidating and organizing biochemical networks. CONCLUSIONS: The software tool Sig2BioPAX is a resource that enables experimental and computational systems biologists to contribute their identified networks and pathways of molecular interactions for integration and reuse with the rest of the research community.

SNAVI: Desktop application for analysis and visualization of large-scale signaling networks.

BACKGROUND: Studies of cellular signaling indicate that signal transduction pathways combine to form large networks of interactions. Viewing protein-protein and ligand-protein interactions as graphs (networks), where biomolecules are represented as nodes and their interactions are represented as links, is a promising approach for integrating experimental results from different sources to achieve a systematic understanding of the molecular mechanisms driving cell phenotype. The emergence of large-scale signaling networks provides an opportunity for topological statistical analysis while visualization of such networks represents a challenge. RESULTS: SNAVI is Windows-based desktop application that implements standard network analysis methods to compute the clustering, connectivity distribution, and detection of network motifs, as well as provides means to visualize networks and network motifs. SNAVI is capable of generating linked web pages from network datasets loaded in text format. SNAVI can also create networks from lists of gene or protein names. CONCLUSION: SNAVI is a useful tool for analyzing, visualizing and sharing cell signaling data. SNAVI is open source free software. The installation may be downloaded from: http://snavi.googlecode.com. The source code can be accessed from: http://snavi.googlecode.com/svn/trunk.