Automated next-generation profiling of genomic alterations in human cancers.

The lack of validated, distributed comprehensive genomic profiling assays for patients with cancer inhibits access to precision oncology treatment. To address this, we describe elio tissue complete, which has been FDA-cleared for examination of 505 cancer-related genes. Independent analyses of clinically and biologically relevant sequence changes across 170 clinical tumor samples using MSK-IMPACT, FoundationOne, and PCR-based methods reveals a positive percent agreement of >97%.

Amyloidosis Masquerading as Alcohol-Related Cirrhosis.

Amyloidosis can affect multiple organs, and involvement of the heart is the most common cause of death. Signs and symptoms vary depending upon the organ system affected by amyloid. Liver involvement is often seen, but symptoms are usually mild and nonspecific in isolated hepatic amyloidosis.

Spatial clusters and temporal trends of malignant melanoma mortality in Ecuador.

Objective: The aim of this study is two fold. First, it describes the temporal trends of malignant melanoma mortality from 2000 to 2016 in Ecuador. Second, it analyzes the spatial clusters of high mortality rates due to malignant melanoma in the country, from 2011 to 2016.

Overview of "Systematic Reviews" of the Built Environment's Effects on Mental Health.

Good mental health is related to mental and psychological well-being, and there is growing interest in the potential role of the built environment on mental health, yet the evidence base underpinning the direct or indirect effects of the built environment is not fully clear. The aim of this overview is to assess the effect of the built environment on mental health-related outcomes. .

Spatial patterns of leptospirosis in Ecuador, 2013-2018.

Background: Leptospirosis is a zoonotic disease that is considered an important public health problem in tropical regions and the world's poorest countries.

Methods: In this ecological study, we included cases of leptospirosis reported in Ecuador from 2013 to 2018. Spatial autocorrelation was evaluated through the global Moran I index and spatial-temporal scan statistics were used to identify high-risk clusters.

McGregor inguinal flap for coverage of large soft tissue losses due to high-voltage electrical burns in the upper limb: a retrospective study.

High-voltage electrical burns are potentially devastating and they are associated with significant morbidity and mortality. Due to vascular damage and progressive tissue necrosis produced by electrical burns, there is a large controversy regarding the ideal reconstructive technique for cutaneous coverage of severe lesions in the upper limb. This study aims to analyze our experience using the McGregor inguinal flap technique, for the coverage of large soft tissue losses produced by high-voltage electric burns in the upper limb.

99mTc-MIBI Uptake in a Benign Thymic Cyst.

A 34-year-old man with end-stage renal failure status post rejection of a deceased donor kidney transplant presented with bone pain in the setting of elevated serum parathyroid hormone and calcium levels. A Tc-MIBI SPECT/CT was performed before planned subtotal parathyroidectomy. SPECT/CT imaging revealed a 1.

Spatial analysis of dengue, cysticercosis and Chagas disease mortality in Ecuador, 2011-2016.

Background: Neglected tropical diseases (NTDs) continue to be an important cause of disability and mortality in the poorest tropical and subtropical areas.

Methods: This is an ecological study. We included all death certificates with dengue, cysticercosis and Chagas disease in Ecuador from 2011 to 2016.

Trends and Spatial Patterns of Oral Cancer Mortality in Ecuador, 2001-2016.

The aims of this study were to describe the temporal trend of OC from 2001 to 2016 and to analyze the space and space-time clusters of high mortality due to OC in Ecuador from 2011 to 2016. . The present study is a mixed ecological study; the time trends were obtained using a Joinpoint regression model, space-time scan statistics was used to identify high-risk clusters, and Global Moran I index was calculated.

Oncogenic K-Ras regulates bioactive sphingolipids in a sphingosine kinase 1-dependent manner.

Sphingosine kinase 1 (SK1) is an important enzyme involved in the production of the bioactive lipid sphingosine 1-phosphate (S1P). SK1 is overexpressed in many forms of cancer, however, the contribution of SK1 to cancer progression is still unclear. One of the best characterized mutations found in several forms of human cancer is an activating point mutation in the Ras oncogene, which disrupts its GTPase activity and leads to stimulation of the MEK/ERK pathway.

Still benched on its way to the bedside: sphingosine kinase 1 as an emerging target in cancer chemotherapy.

For several decades, lipid biologists have investigated how sphingolipids contribute to physiology, cell biology, and cell fate. Foremost among these discoveries is the finding that the bioactive sphingolipids ceramide, sphingosine, and sphingosine-1-phosphate (S1P) have diverse and often opposing effects on cell fate. Interestingly, these bioactive sphingolipids can be interconverted by just a few enzymatic reactions.

Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A.

The mechanisms by which sphingosine kinase-1 (SK-1)/sphingosine 1-phosphate (S1P) activation contributes to imatinib resistance in chronic myeloid leukemia (CML) are unknown. We show herein that increased SK-1/S1P enhances Bcr-Abl1 protein stability, through inhibition of its proteasomal degradation in imatinib-resistant K562/IMA-3 and LAMA-4/IMA human CML cells. In fact, Bcr-Abl1 stability was enhanced by ectopic SK-1 expression.

Regulation of CC ligand 5/RANTES by acid sphingomyelinase and acid ceramidase.

Acid sphingomyelinase (aSMase) generates the bioactive lipid ceramide (Cer) from hydrolysis of sphingomyelin (SM). However, its precise roles in regulating specific sphingolipid-mediated biological processes remain ill defined. Interestingly, the aSMase gene gives rise to two distinct enzymes, lysosomal sphingomyelinase (L-SMase) and secretory sphingomyelinase (S-SMase) via alternative trafficking of a shared protein precursor.

An overview of sphingolipid metabolism: from synthesis to breakdown.

Sphingolipids constitute a class of lipids defined by their eighteen carbon amino-alcohol backbones which are synthesized in the ER from nonsphingolipid precursors. Modification of this basic structure is what gives rise to the vast family of sphingolipids that play significant roles in membrane biology and provide many bioactive metabolites that regulate cell function. Despite the diversity of structure and function of sphingolipids, their creation and destruction are governed by common synthetic and catabolic pathways.

Role of sphingosine kinase-1 in paracrine/transcellular angiogenesis and lymphangiogenesis in vitro.

Sphingosine-1-phosphate (S1P) is an important bioactive sphingolipid involved in angiogenesis and lymphangiogenesis, 2 important processes that influence the growth, survival, and spread of tumors. S1P acts as an extracellular mediator through binding to 5 highly specific S1P receptors, S1P(1-5). Sphingosine kinase-1 (SK1), one of 2 known sphingosine kinase enzymes responsible for S1P production, appears to be overexpressed in many tumors.

Acid ceramidase upregulation in prostate cancer cells confers resistance to radiation: AC inhibition, a potential radiosensitizer.

Radiation resistance in a subset of prostate tumors remains a challenge to prostate cancer radiotherapy. The current study on the effects of radiation on prostate cancer cells reveals that radiation programs an unpredicted resistance mechanism by upregulating acid ceramidase (AC). Irradiated cells demonstrated limited changes of ceramide levels while elevating levels of sphingosine and sphingosine-1-phosphate.

Sphingosine kinase 1 is up-regulated during hypoxia in U87MG glioma cells. Role of hypoxia-inducible factors 1 and 2.

Sphingosine 1-phosphate (S1P), a sphingolipid metabolite that plays an important role in the regulation of cell survival, growth, migration, and angiogenesis, acts both inside the cells and as an extracellular mediator through binding to five G protein-coupled receptors (S1P(1-5)). Sphingosine kinase 1 (SK1), the enzyme responsible for S1P production, is overexpressed in many solid tumors, including gliomas. One common feature of these tumors is the presence of "hypoxic regions," characterized by cells expressing high levels of hypoxia-inducible factors HIF-1alpha and HIF-2alpha, two transcription regulators that modulate the levels of proteins with crucial roles in tumor progression.