Frederick National Laboratory for Cancer Research

Clinical and genetic risk factors for apolipoprotein L1-mediated chronic kidney disease in people of African ancestry with HIV

PURPOSE OF REVIEW: To summarize current understanding of the epidemiology, pathogenesis and management of HIV-Associated Nephropathy (HIVAN) and other forms of Apolipoprotein L1 (APOL1)-mediated chronic kidney disease (CKD) in people of African ancestry with HIV. RECENT FINDINGS:...

Dual inhibition of JAK and MEK suppresses T-cell acute lymphoblastic leukemia induced by mutant IL7R and RASGRP1 overexpression

Gain-of-function mutant IL-7Rα (mutIL7R) occurs in approximately 10% of patients with Tcell acute lymphoblastic leukemia (T-ALL), an aggressive pediatric cancer. Nearly half of patients with T-ALLs also overexpress RAS guanyl nucleotide exchange factor (RASGRP1), an activator of...

Endogenous anti-Ebola virus GP 1,2 antibodies interfere with detection of secreted glycoprotein in the blood of EVD patients

ABSTRACT Ebola disease (EBOD) is a highly infectious disease with severe hemorrhagic symptoms. It is caused by orthoebolaviruses , which include the Ebola virus ( Orthoebolavirus zairense ) (EBOV) causing Ebola virus disease (EVD), the most lethal EBOD to humans. Through co-trans...

Environmental recurrence selects a costly memory-use policy across two operator bundles without a resolved one-bit population benefit

This research preprint and reproducibility package reports three prospectively specified abstract computational studies of a supplied one-record private cache with a fixed one-proposal opportunity cost. Across the original 32-individual model and an independently implemented 32-l...

Mutational profiles of hepatocellular carcinoma that arose in outbred mice after heavy-ion particle and γ-ray radiation

Cancer risk estimation from space radiation is challenged by the lack of relevant experimental and epidemiological data for human exposure to the high-charge, high-energy (HZE) ions that predominate in deep space environments. Genetically diverse outbred mice provide an effective...

Population state changes the transfer value of organized variation in a finite-population model

Historically acquired variation biases can facilitate adaptation, but their value may change as a population moves through a new environment. We studied a two-dimensional model comparing an inherited variation orientation with a quarter-turned control of identical covariance eige...

Environmental recurrence changes the transmission advantage of private memory in a finite-budget population model

Using stored information may help a strategy spread without improving every population-performance endpoint. We distinguish these outcomes in an abstract 32-individual, 32-bit population model with private one-record memory, inherited strategy labels and an equal objective-evalua...

Environmental recurrence changes the transmission advantage of private memory in a finite-budget population model

Using stored information may help a strategy spread without improving every population-performance endpoint. We distinguish these outcomes in an abstract 32-individual, 32-bit population model with private one-record memory, inherited strategy labels and an equal objective-evalua...

Exploratory proteomic analysis of idiopathic pulmonary fibrosis and fibrotic hypersensitivity pneumonitis using data-independent acquisition

Idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP) are two distinct interstitial lung diseases often showing similar clinical features, making differentiation challenging. Precise diagnosis is essential because treatment strategies for these condi...

Oral Fungal Infection Impacts Epithelial Innate Immunity to Promote Local and Distal Squamous Cell Carcinoma Progression

Abstract Fungi have been detected within human tumors and shown to support tumor progression. A better understanding of how intratumoral fungi evade innate immunity, remodel the tumor microenvironment (TME), and promote tumorigenesis may provide insights into cancer pathogenesis...

Molecular Glue Degraders in Early Development for Cancer Therapy

Molecular glue degraders are an emerging class of small molecule allosteric modulators that induce or stabilize protein-protein interactions, enabling targeted degradation of previously intractable proteins. By redirecting E3 ligases to recognize neosubstrates, proteins that are...

Measurement of binding antibodies to SARS-CoV-2 variants elicited by natural infection and COVID-19 vaccines in a sub-Saharan African population

Abstract Data on immune responses to COVID-19 vaccination in West and Central Africa remain limited, particularly with respect to antibody (Ab) binding across SARS-CoV-2 variants and for different types of vaccine platforms. We assessed anti-spike (anti-S) antibody binding to nin...

Phosphorylation Protects Oncogenic RAS from LZTR1-Mediated Degradation

Oncogenic KRAS and NRAS mutations are common in hematologic malignancies, but how they signal is less well characterized than in carcinomas. To uncover novel RAS biology and potential therapeutic vulnerabilities, we employed a multi-omics screening approach in multiple myeloma to...

Overcoming immune checkpoint inhibitor-mediated T-cell exhaustion with a TCR β chain-directed selective dual T-cell activator

Abstract Background Resistance to immune checkpoint inhibition (ICI) using antibodies against the PD-1/PD-L1 axis remains a significant clinical challenge. Here, we report that combination of anti-PD-1 with a bifunctional fusion molecule, anti-TCRβ-IL-2, comprised of a monovalent...

Single-cell profiling of peripheral blood mononuclear cells in diverse men with prostate cancer reveals a fatal disease-associated immune signature

Abstract Alterations in peripheral immunity may contribute to fatal prostate cancer and the excessive disease burden among African American (AA) men. Thus, we investigated peripheral immunity in prostate cancer patients in association with disease outcome and AA descent. We perfo...

Targeting Oncogenic KRAS Using Peptide Nucleic Acid Oligomers Attached to Cell-Penetrating Peptides

Approximately 30% of tumors contain an activating mutation in the oncogene KRAS, leading to increased cell proliferation that often promotes non-small cell lung cancers, colorectal adenocarcinomas, pancreatic ductal adenocarcinomas (PDAC), and other cancers. Among the most common...

Therapeutic NAMPT inhibition reveals a targetable metabolic vulnerability in neuroblastoma

Abstract Background Neuroblastoma (NB) remains a major cause of pediatric cancer mortality for which new therapeutic strategies are needed. Exploitation of reprogrammed metabolic pathways offers an opportunity for cell-type specific anticancer therapeutics. To identify pediatric...

A compendium of next-generation patient-derived models for diverse cancers

Abstract The development of new therapeutics and the validation of pathogenetic cancer mechanisms require representative laboratory models 1,2 . However, existing collections represent only a fraction of the diversity observed in human cancer 2–4 . Recent technologies have enable...

The establishment of prostate-specific, SKP2 humanized mice by CRISPR knock-in method reveals neoplastic initiation and microenvironmental reprogramming

Abstract A recent study has shown that SKP2 inactivation can prevent cancer initiation by extension of total cell cycle duration without perturbing normal division, which suggests a new strategy for cancer prevention. However, direct in vivo evidence for human SKP2 on cancer init...