Digital Profiling of Tumor Extracellular Vesicle-Associated RNAs Directly from Unprocessed Blood Plasma.

Tumor-derived extracellular vesicle (tEV)-associated RNAs hold promise as diagnostic biomarkers, but their clinical use is hindered by the rarity of tEVs among nontumor EVs. Here, we present EV-CLIP, a highly sensitive droplet-based digital method for profiling EV RNA. EV-CLIP utilizes the fusion of EVs with charged liposomes (CLIPs) in a microfluidic chip.

Structure-Based QSAR Modeling of RET Kinase Inhibitors from 49 Different 5,6-Fused Bicyclic Heteroaromatic Cores to Patent-Driven Validation.

RET receptor tyrosine kinase is crucial for nerve and tissue development but can be an important oncogenic driver. This study focuses on exploring the design principles of potent RET inhibitors through molecular docking and 3D-QSAR modeling of 5,6-fused bicyclic heteroaromatic derivatives. First of all, RET inhibitors of 49 different bicyclic substructures were collected from five different data sources and selected through molecular docking simulations.

Denfivontinib activates effector T-cells through NLRP3-inflammasome, yielding potent anticancer effects by combination with pembrolizumab.

Various combination therapies have been investigated to overcome the limitations of using immune checkpoint inhibitors. However, determining the optimal combination therapy remains challenging. To overcome the therapeutical limitation, we conducted a translational research to elucidate the mechanisms by which AXL inhibition enhances the anti-tumor effects when combined with anti-PD-1 antibody therapy.

NO classifier prediction of anti neuroinflammatory agents using text mining of 3D molecular fingerprints.

CNS Drug discovery has been challenging due to the lack of clarity on CNS diseases' basic biological and pathological mechanisms. Despite the difficulty, some CNS drugs have been developed based on phenotypic effects. Herein, we propose a phenotype-structure relationship model, which predicts an anti-neuroinflammatory potency based on 3D molecular structures of the phenotype-active or inactive compounds without specifying targets.

Side Chain Investigation of Imidazopyridazine as a Hinge Binder for Targeting Actionable Mutations of RET Kinase.

Actionable mutations of RET kinase have been identified as oncogenic drivers of solid tumors, including thyroid cancer, metastatic colorectal cancer, and nonsmall cell lung cancer. Although multikinase inhibitors and RET selective inhibitors are used to treat patients with RET alterations, there is insufficient research addressing certain issues: which actionable mutations arise from these therapies, how to improve the clinical response rate to RET inhibitors, and how to design new inhibitors to overcome drug resistance. Therefore, the development of sophisticated tool compounds is required to investigate the molecular mechanisms of actionable mutations and to develop breakthrough therapeutics for different RET alterations.

The role of local ablative therapy in patients with advanced invasive mucinous adenocarcinoma of the lung.

Purpose: Invasive mucinous adenocarcinoma (IMA) of the lungs is a rare subtype of lung adenocarcinoma with a limited understanding of its prognosis, particularly in advanced stages. This study aimed to assess the prognosis of patients with advanced IMA by focusing on treatment modalities.

Methods: This single-center retrospective study evaluated 33 patients with IMAs diagnosed with advanced-stage disease or disease progression after curative treatment between 2011 and 2021.

Case report: Pathological complete response to neoadjuvant brigatinib in stage III non-small cell lung cancer with rearrangement.

Purpose: The use of neoadjuvant anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKIs) has not been extensively explored. The current case report highlights the notable pathological complete response (pCR) achieved following neoadjuvant brigatinib therapy in a patient with stage IIIA ALK-positive non-small cell lung cancer (NSCLC).

Case Presentation: A 32-year-old male presented with incidental lung lesions, ultimately diagnosed as clinical stage T3N1M0, IIIA NSCLC with an gene rearrangement.

Comparison of the Pharmacokinetics of Gadolinium-Based and Iron Oxide-Based Contrast Agents inside the Lymphatic Structure using Magnetic Resonance Lymphangiography.

Purpose: Gadolinium (Gd)-based contrast agents are primarily used for contrast-enhanced magnetic resonance lymphangiography (MRL). However, overcoming venous contamination issues remains challenging. This study aims to assess the MRL efficacy of the newly developed iron-based contrast agent (INV-001) that is specially designed to mitigate venous contamination issues.

Additional local therapy before disease progression for EGFR-mutated advanced lung cancer: a systematic review and meta-analysis.

Background: International guidelines recommend the use of local therapy (LT) to limited progression in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). However, the use of LT before disease progression has not been extensively analyzed. This meta-analysis evaluates the efficacy and safety of administering additional LT in conjunction with first-line EGFR-tyrosine kinase inhibitors (TKIs) before disease progression in patients with EGFR-mutated advanced NSCLC.

GPCR-IPL score: multilevel featurization of GPCR-ligand interaction patterns and prediction of ligand functions from selectivity to biased activation.

G-protein-coupled receptors (GPCRs) mediate diverse cell signaling cascades after recognizing extracellular ligands. Despite the successful history of known GPCR drugs, a lack of mechanistic insight into GPCR challenges both the deorphanization of some GPCRs and optimization of the structure-activity relationship of their ligands. Notably, replacing a small substituent on a GPCR ligand can significantly alter extracellular GPCR-ligand interaction patterns and motion of transmembrane helices in turn to occur post-binding events of the ligand.

CD81 and CD82 expressing tumor-infiltrating lymphocytes in the NSCLC tumor microenvironment play a crucial role in T-cell activation and cytokine production.

Introduction: To understand the immune system within the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC), it is crucial to elucidate the characteristics of molecules associated with T cell activation.

Methods: We conducted an in-depth analysis using single-cell RNA sequencing data obtained from tissue samples of 19 NSCLC patients. T cells were classified based on the Tumor Proportion Score (TPS) within the tumor region, and molecular markers associated with activation and exhaustion were analyzed in T cells from high TPS areas.

Next-generation sequencing using tissue specimen collected with a 1.1 mm-diameter cryoprobe in patients with lung cancer.

Background And Objective: Next-generation sequencing (NGS) analysis is considered standard for lung cancer diagnosis in clinical practice. Little is known about the feasibility of NGS using tumour tissue sampled with a 1.1 mm-diameter cryoprobe.

An RORα agonist, ODH-08, inhibits fibrogenic activation of hepatic stellate cells via suppression of SMAD3.

Aims: Hepatic fibrosis is a dynamic process characterized by the net accumulation of an extracellular matrix resulting from chronic liver injury such as nonalcoholic steatohepatitis. Activation of hepatic stellate cells (HSCs) plays a role in transdifferentiation of quiescent cells into fibrogenic myofibroblasts. We aimed to examine the function of retinoic acid receptor-related orphan receptor alpha (RORα) and its novel agonistic ligand, 1-(4-benzyloxybenzyl)-3-(2-dimethylaminoethyl)-thiourea (ODH-08) against activation of HSCs using hepatic fibrosis mouse models.

Sequence-Type Classification of Brain MRI for Acute Stroke Using a Self-Supervised Machine Learning Algorithm.

We propose a self-supervised machine learning (ML) algorithm for sequence-type classification of brain MRI using a supervisory signal from DICOM metadata (i.e., a rule-based virtual label).

Development of the Korean Association for Lung Cancer Clinical Practice Guidelines: Recommendations on Radial Probe Endobronchial Ultrasound for Diagnosing Lung Cancer - An Updated Meta-Analysis.

Purpose: Radial probe endobronchial ultrasound (RP-EBUS) accurately locates peripheral lung lesions (PLLs) during transbronchial biopsy (TBB). We performed an updated meta-analysis of the diagnostic yield of TBB for PLLs using RP-EBUS to generate recommendations for the development of the Korean Association of Lung Cancer guidelines.

Materials And Methods: We systematically searched MEDLINE and EMBASE (from January 2013 to December 2022), and performed a meta-analysis using R software.

CCR8 as a Therapeutic Novel Target: Omics-Integrated Comprehensive Analysis for Systematically Prioritizing Indications.

Target identification is a crucial process in drug development, aiming to identify key proteins, genes, and signal pathways involved in disease progression and their relevance in potential therapeutic interventions. While C-C chemokine receptor 8 (CCR8) has been investigated as a candidate anti-cancer target, comprehensive multi-omics analyzes across various indications are limited. In this study, we conducted an extensive bioinformatics analysis integrating genomics, proteomics, and transcriptomics data to establish CCR8 as a promising anti-cancer drug target.