Kidney Function and Body Composition in Adult Survivors of Unilateral, Non-Syndromic Wilms Tumor: A Report From the St. Jude Lifetime Cohort Study.

Background: The relationships among treatment exposures, body composition, and estimated glomerular filtration rate (eGFR) in adult survivors of Wilms tumor have not been well studied.

Methods: We evaluated body composition with dual-energy x-ray absorptiometry (DXA) and eGFR with the updated Chronic Kidney Disease Epidemiology Collaboration equations (creatinine only-eGFR, cystatin C only-eGFR, creatinine and cystatin C-eGFR) without race in 134 adults previously treated for unilateral, non-syndromic Wilms tumor at St. Jude Children's Research Hospital between 1964 and 2004 with chemotherapy and with (hemiabdomen [HA] or whole abdomen [WA]) or without radiation therapy (RT).

The Role of eHsp90 in Extracellular Matrix Remodeling, Tumor Invasiveness, and Metastasis.

Identifying proteins that act in tumor invasiveness and metastasis remains a critical unmet need in our search for effective cancer therapy. Hsp90, an abundant intracellular chaperone protein, plays a key role in maintaining cell homeostasis, and its elevated activity is pivotal in cancer progression. Due to the reliance of cancer cells on Hsp90's chaperone function to sustain tumor growth and spread, Hsp90 inhibitors have been the subject of numerous clinical trials over the past two decades.

The accuracy of estimating equations for the evaluation of kidney function in adult survivors of unilateral, nonmetastatic, non-syndromic Wilms tumor: A pilot study from the St. Jude Lifetime Cohort Study.

Background: Adult survivors of unilateral, nonmetastatic, non-syndromic Wilms tumor (WT) treated with whole abdomen radiation therapy (WART) are at risk for impaired kidney function. The impact of bias and accuracy on estimated glomerular filtration rate (eGFR) among adult survivors of WT has not been well documented.

Procedure: We clinically evaluated male and female WT survivors with creatinine and cystatin C, calculated eGFR using the Chronic Kidney Disease-Epidemiology equations with and without cystatin C, and measured Tc diethylenetriamine pentaacetic acid (DTPA) plasma clearance.

Sea level rise and the drivers of daily water levels in the Sacramento-San Joaquin Delta.

Water levels in deltas and estuaries vary on multiple timescales due to coastal, hydrologic, meteorologic, geologic, and anthropogenic factors. These diverse factors increase the uncertainty of, and may bias, relative sea level rise (RSLR) estimates. Here, we evaluate RSLR in San Francisco Bay and the Sacramento-San Joaquin Delta, USA by applying a physics-based, nonlinear regression to 50 tide gauges that determines the spatially varying controls on daily mean water level for water years 2004-2022.

Extracellular Hsp90 Binds to and Aligns Collagen-1 to Enhance Breast Cancer Cell Invasiveness.

Cancer cell-secreted eHsp90 binds and activates proteins in the tumor microenvironment crucial in cancer invasion. Therefore, targeting eHsp90 could inhibit invasion, preventing metastasis-the leading cause of cancer-related mortality. Previous eHsp90 studies have solely focused on its role in cancer invasion through the 2D basement membrane (BM), a form of extracellular matrix (ECM) that lines the epithelial compartment.

COVID-19 monitoring with sparse sampling of sewered and non-sewered wastewater in urban and rural communities.

Equitable SARS-CoV-2 surveillance in low-resource communities lacking centralized sewers is critical as wastewater-based epidemiology (WBE) progresses. However, large-scale studies on SARS-CoV-2 detection in wastewater from low-and middle-income countries is limited because of economic and technical reasons. In this study, wastewater samples were collected twice a month from 186 urban and rural subdistricts in nine provinces of Thailand mostly having decentralized and non-sewered sanitation infrastructure and analyzed for SARS-CoV-2 RNA variants using allele-specific RT-qPCR.

Repurposing Antimalarial Pyronaridine as a DNA Repair Inhibitor to Exploit the Full Potential of Gold-Nanoparticle-Mediated Radiation Response.

Radiation therapy (RT) is frequently used to locally treat tumors. One of the major issues in RT is normal tissue toxicity; thus, it is necessary to limit dose escalation for enhanced local control in patients that have locally advanced tumors. Integrating radiosensitizing agents such as gold nanoparticles (GNPs) into RT has been shown to greatly increase the cure rate of solid tumors.

Extracellular Heat Shock Protein-90 (eHsp90): Everything You Need to Know.

"Extracellular" Heat Shock Protein-90 (Hsp90) was initially reported in the 1970s but was not formally recognized until 2008 at the 4th International Conference on The Hsp90 Chaperone Machine (Monastery Seeon, Germany). Studies presented under the topic of "extracellular Hsp90 (eHsp90)" at the conference provided direct evidence for eHsp90's involvement in cancer invasion and skin wound healing. Over the past 15 years, studies have focused on the secretion, action, biological function, therapeutic targeting, preclinical evaluations, and clinical utility of eHsp90 using wound healing, tissue fibrosis, and tumour models both in vitro and in vivo.

Angiogenin and plexin-B2 axis promotes glioblastoma progression by enhancing invasion, vascular association, proliferation and survival.

Background: Angiogenin is a multifunctional secreted ribonuclease that is upregulated in human cancers and downregulated or mutationally inactivated in neurodegenerative diseases. A role for angiogenin in glioblastoma was inferred from the inverse correlation of angiogenin expression with patient survival but had not been experimentally investigated.

Methods: Angiogenin knockout mice were generated and the effect of angiogenin deficiency on glioblastoma progression was examined.

Modulation of ERCC1-XPF Heterodimerization Inhibition Structural Modification of Small Molecule Inhibitor Side-Chains.

Inhibition of DNA repair enzymes is an attractive target for increasing the efficacy of DNA damaging chemotherapies. The ERCC1-XPF heterodimer is a key endonuclease in numerous single and double strand break repair processes, and inhibition of the heterodimerization has previously been shown to sensitize cancer cells to DNA damage. In this work, the previously reported ERCC1-XPF inhibitor 4 was used as the starting point for an study of further modifications of the piperazine side-chain.

Inhibition of triple negative breast cancer metastasis and invasiveness by novel drugs that target epithelial to mesenchymal transition.

Invasive breast cancer (BrCa) is predicted to affect 1 in 9 women in a lifetime;1 in 32 will die from this disease. The most aggressive forms of BrCa, basal-like/triple-negative phenotype (TNBC), are challenging to treat and result in higher mortality due high number of metastatic cases. There is a paucity of options for TNBC treatment, which highlights the need for additional innovative treatment approaches.

Evolving tides aggravate nuisance flooding along the U.S. coastline.

Nuisance flooding (NF) is defined as minor, nondestructive flooding that causes substantial, accumulating socioeconomic impacts to coastal communities. While sea-level rise is the main driver for the observed increase in NF events in the United States, we show here that secular changes in tides also contribute. An analysis of 40 tidal gauge records from U.

Kidney Function after Treatment for Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study.

Background: Survivors of childhood cancer may be at increased risk for treatment-related kidney dysfunction. Although associations with acute kidney toxicity are well described, evidence informing late kidney sequelae is less robust.

Methods: To define the prevalence of and risk factors for impaired kidney function among adult survivors of childhood cancer who had been diagnosed ≥10 years earlier, we evaluated kidney function (eGFR and proteinuria).

Assessing the Impact of Factors that Influence the Ketogenic Response to Varying Doses of Medium Chain Triglyceride (MCT) Oil.

Unlabelled: Objectives, Design, Setting: The ketogenic effect of medium chain triglyceride (MCT) oil offers potential for Alzheimer's disease prevention and treatment. Limited literature suggests a linear B-hyroxybutyrate (BHB) response to increasing MCT doses. This pharmacokinetic study evaluates factors affecting BHB response in three subject groups.

Design, synthesis and in vitro cell-free/cell-based biological evaluations of novel ERCC1-XPF inhibitors targeting DNA repair pathway.

The structure-specific ERCC1-XPF endonuclease is essential for repairing bulky DNA lesions and helix distortions induced by UV radiation, which forms cyclobutane pyrimidine dimers (CPDs), or chemicals that crosslink DNA strands such as cyclophosphamide and platinum-based chemotherapeutic agents. Inhibition of the ERCC1-XPF endonuclease activity has been shown to sensitize cancer cells to these chemotherapeutic agents. In this study, we have conducted a structure activity relationship analysis based around the previously identified hit compound, 4-((6-chloro-2-methoxyacridin-9-yl)amino)-2-((4-methylpiperazin1-yl)methyl)phenol (F06), as a reference compound.

Long-term renal function after treatment for unilateral, nonsyndromic Wilms tumor. A report from the St. Jude Lifetime Cohort Study.

Background: The impact of specific treatment modalities on long-term renal function and blood pressure among adult survivors of Wilms tumor (WT) has not been well documented.

Methods: Among 40 WT survivors and 35 noncancer controls, we estimated the glomerular filtration rate (eGFR) using the Chronic Kidney Disease-Epidemiology (CKD-EPI) equations with and without cystatin C, obtained 24-hour ambulatory blood pressure readings, and, among survivors only, measured Tc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. Survivors were treated with unilateral nephrectomy and nonnephrotoxic chemotherapy.

Computer-aided drug design of small molecule inhibitors of the ERCC1-XPF protein-protein interaction.

The heterodimer of DNA excision repair protein ERCC-1 and DNA repair endonuclease XPF (ERCC1-XPF) is a 5'-3' structure-specific endonuclease essential for the nucleotide excision repair (NER) pathway, and it is also involved in other DNA repair pathways. In cancer cells, ERCC1-XPF plays a central role in repairing DNA damage induced by chemotherapeutics including platinum-based and cross-linking agents; thus, its inhibition is a promising strategy to enhance the effect of these therapies. In this study, we rationally modified the structure of F06, a small molecule inhibitor of the ERCC1-XPF interaction (Molecular Pharmacology, 84, 2013 and 12), to improve its binding to the target.

Sequential and Environmental Dependence of Conformation in a Small Opioid Peptide.

We report the structural characterization of the μ-selective endogenous opioid endomorphin-1 (EM-1) via an array of nuclear magnetic resonance experiments in both aqueous conditions and, for the first time, in isotropic lipid bicelles, which mimic its endogenous environment. Consistent with computationally derived hypotheses, EM-1 is found to significantly populate a compact, turn-like structure in aqueous solution. This structure is only present as a minor species when the peptide is subjected to a lipid environment, in which the presented NMR data suggests that the major conformer of EM-1 lacks internal hydrogen bonds.

Hepatocyte Stress Increases Expression of Yes-Associated Protein and Transcriptional Coactivator With PDZ-Binding Motif in Hepatocytes to Promote Parenchymal Inflammation and Fibrosis.

Background And Aims: Activated hepatocytes are hypothesized to be a major source of signals that drive cirrhosis, but the biochemical pathways that convert hepatocytes into such a state are unclear. We examined the role of the Hippo pathway transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in hepatocytes to facilitate cell-cell interactions that stimulate liver inflammation and fibrosis.

Approach And Results: Using a variety of genetic, metabolic, and liver injury models in mice, we manipulated Hippo signaling in hepatocytes and examined its effects in nonparenchymal cells to promote liver inflammation and fibrosis.