Diphenyleneiodonium Triggers Cell Death of Acute Myeloid Leukemia Cells by Blocking the Mitochondrial Respiratory Chain, and Synergizes with Cytarabine.

Acute myeloid leukemia (AML) is characterized by the accumulation of undifferentiated blast cells in the bone marrow and blood. In most cases of AML, relapse frequently occurs due to resistance to chemotherapy. Compelling research results indicate that drug resistance in cancer cells is highly dependent on the intracellular levels of reactive oxygen species (ROS).

Targeting Reactive Oxygen Species Metabolism to Induce Myeloma Cell Death.

Multiple myeloma (MM) is a common hematological disease characterized by the accumulation of clonal malignant plasma cells in the bone marrow. Over the past two decades, new therapeutic strategies have significantly improved the treatment outcome and patients survival. Nevertheless, most MM patients relapse underlying the need of new therapeutic approaches.

Characterization of NADPH Oxidase Expression and Activity in Acute Myeloid Leukemia Cell Lines: A Correlation with the Differentiation Status.

In acute myeloid leukemia (AML), a low level of reactive oxygen species (ROS) is associated with leukemic stem cell (LSC) quiescence, whereas a high level promotes blast proliferation. ROS homeostasis relies on a tightly-regulated balance between the antioxidant and oxidant systems. Among the oxidants, NADPH oxidases (NOX) generate ROS as a physiological function.

Analysis of the Neuroproteome Associated With Cell Therapy After Intranigral Grafting in a Mouse Model of Parkinson Disease.

Advances in large-scale proteomics analysis have been very useful in understanding pathogenesis of diseases and elaborating therapeutic strategies. Proteomics has been employed to study Parkinson disease (PD); however, sparse studies reported proteome investigation after cell therapy approaches. In this study, we used liquid chromatography-tandem mass spectrometry and systems biology to identify differentially expressed proteins in a translational mouse model of PD after cell therapy.

SK4 oncochannels regulate calcium entry and promote cell migration in KRAS-mutated colorectal cancer.

Background: Colorectal cancer (CRC) metastases are the main cause of CRC mortality. Intracellular Ca2+ regulates cell migration and invasion, key factors for metastases. Ca2+ also activates Ca2+-dependent potassium channels which in turn affect Ca2+ driving force.

Horizontal meta-analysis identifies common deregulated genes across AML subgroups providing a robust prognostic signature.

Advances in transcriptomics have improved our understanding of leukemic development and helped to enhance the stratification of patients. The tendency of transcriptomic studies to combine AML samples, regardless of cytogenetic abnormalities, could lead to bias in differential gene expression analysis because of the differential representation of AML subgroups. Hence, we performed a horizontal meta-analysis that integrated transcriptomic data on AML from multiple studies, to enrich the less frequent cytogenetic subgroups and to uncover common genes involved in the development of AML and response to therapy.

VAS3947 Induces UPR-Mediated Apoptosis through Cysteine Thiol Alkylation in AML Cell Lines.

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) involvement has been established in the oncogenic cell signaling of acute myeloid leukemia (AML) cells and in the crosstalk with their niche. We have shown an expression of NOX subunits in AML cell lines while NOX activity is lacking in the absence of exogenous stimulation. Here, we used AML cell lines as models to investigate the specificity of VAS3947, a current NOX inhibitor.

Acriflavine targets oncogenic STAT5 signaling in myeloid leukemia cells.

Acriflavine (ACF) is an antiseptic with anticancer properties, blocking the growth of solid and haematopoietic tumour cells. Moreover, this compound has been also shown to overcome the resistance of cancer cells to chemotherapeutic agents. ACF has been shown to target hypoxia-inducible factors (HIFs) activity, which are key effectors of hypoxia-mediated chemoresistance.

A comparative study of the capacity of mesenchymal stromal cell lines to form spheroids.

Mesenchymal stem cells (MSC)-spheroid models favor maintenance of stemness, ex vivo expansion and transplantation efficacy. Spheroids may also be considered as useful surrogate models of the hematopoietic niche. However, accessibility to primary cells, from bone marrow (BM) or adipose tissues, may limit their experimental use and the lack of consistency in methods to form spheroids may affect data interpretation.

Pannexin1 Is Associated with Enhanced Epithelial-To-Mesenchymal Transition in Human Patient Breast Cancer Tissues and in Breast Cancer Cell Lines.

Loss of connexin-mediated cell-cell communication is a hallmark of breast cancer progression. Pannexin1 (PANX1), a glycoprotein that shares structural and functional features with connexins and engages in cell communication with its environment, is highly expressed in breast cancer metastatic foci; however, PANX1 contribution to metastatic progression is still obscure. Here we report elevated expression of PANX1 in different breast cancer (BRCA) subtypes using RNA-seq data from The Cancer Genome Atlas (TCGA).

Expression Profiling of Calcium Channels and Calcium-Activated Potassium Channels in Colorectal Cancer.

: Colorectal cancer (CRC) is a highly devastating cancer. Ca-dependent channels are now considered key regulators of tumor progression. In this study, we aimed to investigate the association of non-voltage gated Ca channels and Ca-dependent potassium channels (KCa) with CRC using the transcriptional profile of their genes.

Clinical Performance of Prediction Rules and Nasogastric Lavage for the Evaluation of Upper Gastrointestinal Bleeding: A Retrospective Observational Study.

. The majority of patients with acute upper gastrointestinal bleeding (UGIB) are admitted for urgent endoscopy as it can be difficult to determine who can be safely managed as an outpatient. Our objective was to compare four clinical prediction scoring systems: Glasgow Blatchford Score (GBS) and Clinical Rockall, Adamopoulos, and Tammaro scores in a sample of patients presenting to the emergency department of a large US academic center.

The Diagnostic Yield of Repeated Endoscopic Evaluation in Patients with Gastrointestinal Bleeding and Left Ventricular Assist Devices.

Introduction: Left ventricular assist devices (LVADs) are increasingly common in patients with advanced heart failure. GI bleeding (GIB) occurs in 20-30 % of these patients and can arise anywhere in the GI tract. Given the high rates of GIB in this population, our aim was to determine the diagnostic yield of repeated endoscopic evaluation in these patients.

Management of occluded metal stents in malignant biliary obstruction: similar outcomes with second metal stents compared to plastic stents.

Background: Covered or uncovered self expandable metallic stents (SEMS) placed in patients with malignant biliary obstruction can occlude in 19-40 %, but optimal management is unclear.

Aim: We sought to summarize current evidence regarding management of occluded SEMS in patients with malignant biliary obstruction.

Methods: Two investigators independently searched Pubmed, Embase, and Web of Science using pre-defined search criteria, and reviewed bibliographies of included studies.

The use of GTX as second-line and later chemotherapy for metastatic pancreatic cancer: a retrospective analysis.

Purpose: There are limited data regarding the role of second-line treatment for metastatic pancreatic cancer (mPC) after the failure of initial chemotherapy. No data exist on the use of GTX after the failure of first-line therapy.

Patients And Methods: We identified patients who were given GTX chemotherapy for a diagnosis of mPC after the failure of initial therapy.