Advances in Early Detection of Melanoma and the Future of At-Home Testing.

The past decade has seen numerous advancements in approaches to melanoma detection, each with the common goal to stem the growing incidence of melanoma and its mortality rate. These advancements, while well documented to increase early melanoma detection, have also garnered considerable criticism of their efficacy for improving survival rates. In this review, we discuss the current state of such early detection approaches that do not require direct dermatologist intervention.

STINGing the immune system: lessons learned through a model of G34-mutant pediatric high-grade glioma.

Pediatric high-grade gliomas (pHGGs) are aggressive diseases with poor outcomes. The diverse molecular heterogeneity in these rare tumors and inadequate tumor models have limited the development of effective therapies. In this issue of the JCI, Haase et al.

Metal-Metal Oxide Catalytic Interface Formation and Structural Evolution: A Discovery of Strong Metal-Support Bonding, Ordered Intermetallics, and Single Atoms.

In-depth investigation of metal-metal oxide interactions and their corresponding evolution is of paramount importance to heterogeneous catalysis as it allows the understanding and maneuvering of the structure of catalytic motifs. Herein, using a series of core/shell metal/iron oxide (M/FeO, M = Pd, Pt, Au) nanoparticles and through a combination of and electron and X-ray investigations, we revealed anomalous and dissimilar M-FeO interactions among different systems under reducing conditions. Pd interacts strongly with FeO after high-temperature reductive treatment, featured by the formation of Pd single atoms in the FeO matrix and increased Pd-Fe bonding, while Pt transforms into ordered PtFe intermetallics and Pt single atoms immediately upon the coating of FeO.

Phenotypically distinguishing ESBL-producing pathogens using paper-based surface enhanced Raman sensors.

Antimicrobial stewardship practices are critical in preventing the further erosion of treatment options for bacterial infections. Yet, at the same time, determination of an infection's antimicrobial susceptibility requires multiple rounds of culture and expensive lab automation systems. In this work, we report the use of paper-based surface enhanced Raman spectroscopy (SERS) sensors and portable instrumentation to phenotypically discriminate multi-drug resistance with fewer culture steps than conventional clinical microbiology.

Dynamic Electric Field Alignment of Metal-Organic Framework Microrods.

Alignment of metal-organic framework (MOF) crystals has previously been performed via careful control of oriented MOF growth on substrates, as well as by dynamic magnetic alignment. We show here that bromobenzene-suspended microrod crystals of the MOF NU-1000 can also be dynamically aligned via electric fields, giving rise to rapid electrooptical responses. This method of dynamic MOF alignment opens up new avenues of MOF control which are important for integration of MOFs into switchable electronic devices as well as in other applications such as reconfigurable sensors or optical systems.

Infective endocarditis caused by Klebsiella oxytoca in an intravenous drug user with cancer.

Infective endocarditis caused by Klebsiella species is rare, with most isolates being K. pneumoniae. We report the case of a 24-year-old intravenous drug user with newly diagnosed seminoma who developed K.

Modulation of Glucocorticoid Resistance in Pediatric T-cell Acute Lymphoblastic Leukemia by Increasing BIM Expression with the PI3K/mTOR Inhibitor BEZ235.

Purpose: The aim of our study is to evaluate the preclinical therapeutic activity and mechanism of action of BEZ235, a dual PI3K/mTOR inhibitor, in combination with dexamethasone in acute lymphoblastic leukemia (ALL).

Experimental Design: The cytotoxic effects of BEZ235 and dexamethasone as single agents and in combination were assessed in a panel of ALL cell lines and xenograft models. The underlying mechanism of BEZ235 and dexamethasone was evaluated using immunoblotting, TaqMan RT-PCR, siRNA, immunohistochemistry, and immunoprecipitation.

A Sporadic Case of Advanced Metastatic Cholangiocarcinoma in a Child: A Case Report and Review of Literature.

Cholangiocarcinoma (CC) is a malignancy of the biliary tract that commonly presents in the seventh decade of life, but is extremely rare in children. We report on a sporadic case of malignant CC in an 11-year-old female. Originally presenting with dyspnea, chest x-ray identified multiple pulmonary metastases, and various imaging modalities revealed diffuse disease spread throughout the liver and lungs.

Activity of MM-398, nanoliposomal irinotecan (nal-IRI), in Ewing's family tumor xenografts is associated with high exposure of tumor to drug and high SLFN11 expression.

Purpose: To determine the pharmacokinetics and the antitumor activity in pediatric cancer models of MM-398, a nanoliposomal irinotecan (nal-IRI).

Experimental Design: Mouse plasma and tissue pharmacokinetics of nal-IRI and the current clinical formulation of irinotecan were characterized. In vivo activity of irinotecan and nal-IRI was compared in xenograft models (3 each in nu/nu mice) of Ewing's sarcoma family of tumors (EFT), neuroblastoma (NB), and rhabdomyosarcoma (RMS).

Caspase-dependent Mcl-1 cleavage and effect of Mcl-1 phosphorylation in ABT-737-induced apoptosis in human acute lymphoblastic leukemia cell lines.

ABT-737 is a BH3-mimetic that has a wide spectrum of single-agent activity against acute lymphoblastic leukemia (ALL) cell lines and xenografts. Previously, we reported that in response to ABT-737, ABT-737-resistant ALL cell lines showed an apparent increase in Mcl-1 (an anti-apoptotic Bcl-2 family protein that is not effectively inhibited by ABT-737) while ABT-737-sensitive ALL cell lines showed decreased Mcl-1 levels. Here we explored the mechanism of Mcl-1 cleavage by ABT-737 and the effect of adjacent phosphorylation sites on Mcl-1 cleavage and apoptosis induced by ABT-737 in a human B-lineage ALL cell line.

Association of high-risk scores for obstructive sleep apnea with symptomatic bradyarrhythmias.

Background: Obstructive sleep apnea (OSA) may have an association with bradyarrhythmias but often remains undiagnosed. Our aim was to determine if patients with a high risk of OSA attending our cardiology clinics had an association with symptomatic bradyarrhythmias, as this information might lead to changes in management strategy.

Methods: The Berlin questionnaire was used to assess risk of OSA in 190 patients, and they were divided into high-risk or low-risk groups.

Bcl-2 family of proteins as therapeutic targets in genitourinary neoplasms.

Introduction: Overexpression of antiapoptotic B-cell lymphoma (Bcl-2) proteins confers the dysregulation of apoptosis and results in drug resistance in a variety of cancers, including those of the genitourinary tract. Inhibitors that target prosurvival Bcl-2 proteins are in preclinical and clinical development. The objective of this review is to assess the involvement of Bcl-2 proteins as well as the preclinical and clinical activity of Bcl-2 inhibitors under evaluation for genitourinary neoplasms.

Synergistic activity of rapamycin and dexamethasone in vitro and in vivo in acute lymphoblastic leukemia via cell-cycle arrest and apoptosis.

Activation of the mTOR pathway subsequent to phosphatase and tensin homolog (PTEN) mutation may be associated with glucocorticoid (GC) resistance in acute lymphoblastic leukemia (ALL). The combination activity of rapamycin and dexamethasone in cell lines and xenograft models of ALL was determined. Compared with either drug alone, dexamethasone+rapamycin showed significantly greater apoptosis and cell cycle arrest in some cell lines, and was more frequently seen in T-lineage cell lines with PTEN mutation.

Methotrexate and aminopterin exhibit similar in vitro and in vivo preclinical activity against acute lymphoblastic leukaemia and lymphoma.

Due to the development of neurological toxicity and resistance to methotrexate (MTX), other antifolates have been evaluated for its potential replacement in the treatment of childhood acute lymphoblastic leukaemia (ALL). Aminopterin (AMT) has been suggested to provide clinical advantages over MTX and other antifolates. AMT activity, compared with MTX, was evaluated in ALL and lymphoma preclinical models.