Osimertinib plus anlotinib for advanced NSCLC with acquired EGFR T790M mutation: results from a multicenter phase II study with ctDNA analysis.

Background: Osimertinib is a standard treatment for first- or second-line therapy in patients with non-small cell lung cancer (NSCLC) harboring mutations in the epidermal growth factor receptor (EGFR). However, options are limited for patients with acquired EGFR T790M mutations resistant to first- or second-generation EGFR-tyrosine kinase inhibitors (TKIs). This study assessed the efficacy and safety of combining osimertinib with anlotinib in this patient population and explored circulating tumor DNA (ctDNA) as a biomarker of treatment outcomes.

, a novel rearrangement in lung squamous cell carcinoma and its clinical responses to ALK inhibitors.

Background: Lung cancer is the leading cause of cancer-related death worldwide, of which anaplastic lymphoma kinase fusion positive ( ) non-small cell lung cancer (NSCLC) accounts for 3-7. Here, we identified a new fusion gene (P1, A19) from a patient with advanced lung squamous cell carcinoma (LUSC) by next-generation sequencing (NGS). We aimed to evaluate its oncogenic potential by performing functional studies and tumorigenicity of this fusion protein.

PIM1 kinase promotes EMT-associated osimertinib resistance via regulating GSK3β signaling pathway in EGFR-mutant non-small cell lung cancer.

Acquired resistance is inevitable in the treatment of non-small cell lung cancer (NSCLC) with osimertinib, and one of the primary mechanisms responsible for this resistance is the epithelial-mesenchymal transition (EMT). We identify upregulation of the proviral integration site for Moloney murine leukemia virus 1 (PIM1) and functional inactivation of glycogen synthase kinase 3β (GSK3β) as drivers of EMT-associated osimertinib resistance. Upregulation of PIM1 promotes the growth, invasion, and resistance of osimertinib-resistant cells and is significantly correlated with EMT molecules expression.

PIM1/NF-κB/CCL2 blockade enhances anti-PD-1 therapy response by modulating macrophage infiltration and polarization in tumor microenvironment of NSCLC.

Elevated infiltration of tumor-associated macrophages (TAMs) drives tumor progression and correlates with poor prognosis for various tumor types. Our research identifies that the ablation of the Pim-1 proto-oncogene (PIM1) in non-small cell lung cancer (NSCLC) suppresses TAM infiltration and prevents them from polarizing toward the M2 phenotype, thereby reshaping the tumor immune microenvironment (TME). The predominant mechanism through which PIM1 exerts its impact on macrophage chemotaxis and polarization involves CC motif chemokine ligand 2 (CCL2).

Exploring the protective association between COVID-19 infection and laryngeal cancer: insights from a Mendelian randomization study.

Introduction: Viral infections have been implicated as a risk factor for laryngeal cancer. Given the possible effects of Corona virus disease 2019 (COVID-19) on the laryngeal tissue, we investigated the causal link between COVID-19 and laryngeal cancer using a two-sample Mendelian randomization (MR) approach.

Methods: We utilized genetic data from the 5th Genome-wide association studies (GWAS) edition of the COVID-19 Host Genetics Initiative (published on January 18, 2021) and a large-scale laryngeal cancer GWAS comprising 180 cases and 218,612 controls of European ancestry.

Antitumor immunity and prognosis value elicited by FAT3 and LRP1B co-mutation in endometrial cancer.

Objective: FAT3 and LRP1B are two tumor suppressor genes with high mutation frequency in multiple cancer types, we sought to investigate the prognostic and immunological significance of these two genes in EC.

Methods: Based on a cohort of 502 EC samples, we conducted a comprehensive analysis of its multidimensional data types including genomic, transcriptomic, and clinical information, the potential impact of FAT3 and LRP1B co-mutation on antitumor immune response and prognosis were systematically discussed.

Results: We observed that FAT3 and LRP1B co-mutation was not only defined a dataset with prominently increased TMB, decreased tumor aneuploidy, and specially enriched in MSI-H subtype, but also manifested increased expression of immune-related markers, especially exclusive upregulation of PD-L1 levels and higher PD-L1/CD8A proportion.

Quantification of preexisting lung ground glass opacities on CT for predicting checkpoint inhibitor pneumonitis in advanced non-small cell lung cancer patients.

Background: Immune checkpoint inhibitors (ICIs) can lead to life-threatening pneumonitis, and pre-existing interstitial lung abnormalities (ILAs) are a risk factor for checkpoint inhibitor pneumonitis (CIP). However, the subjective assessment of ILA and the lack of standardized methods restrict its clinical utility as a predictive factor. This study aims to identify non-small cell lung cancer (NSCLC) patients at high risk of CIP using quantitative imaging.

Signal peptide peptidase-like 2b modulates the amyloidogenic pathway and exhibits an Aβ-dependent expression in Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial disorder driven by abnormal amyloid β-peptide (Aβ) levels. In this study, we investigated the role of presenilin-like signal peptide peptidase-like 2b (SPPL2b) in AD pathophysiology and its potential as a druggable target within the Aβ cascade. Exogenous Aβ42 influenced SPPL2b expression in human cell lines and acute mouse brain slices.

Pan-cancer analysis of the prognostic and immunological role of nucleophosmin/nucleoplasmin 3 () and its potential significance in lung adenocarcinoma.

Background: Nucleophosmin/nucleoplasmin 3 (), a member of the NPM protein family, is widely expressed in various human tissues. Although previous studies identified elevated expression in several cancers, a systematic pan-cancer analysis remains lacking. In this study, we conducted a comprehensive analysis of to determine its role in tumorigenesis and tumor development.

Characteristics of T Cells in Single-Cell Datasets of Peripheral Blood and Cerebrospinal Fluid in Alzheimer's Disease Patients.

Background: Alzheimer's disease (AD) is the most common type of dementia, causing a huge socioeconomic burden. In parallel with the widespread uptake of single-cell RNA sequencing (scRNA-seq) technology, there has been a rapid accumulation of data produced by researching AD at single-cell resolution, which is more conductive to explore the neuroimmune-related mechanism of AD.

Objective: To explore the potential features of T cells in the peripheral blood and cerebrospinal fluid of AD patients.

Influence of Tumor Cavitation on Assessing the Clinical Benefit of Anti-PD1 or PD-L1 Inhibitors in Advanced Lung Squamous Cell Carcinoma.

Purpose: A considerable portion of lung squamous cell cancer (LUSC) displays radiographic signs of cavitation. The cavitation of lesions is not accounted for in the prevailing Evaluation Criteria of Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or iRECIST in lung cancer.

Mitochondrial hypermetabolism precedes impaired autophagy and synaptic disorganization in App knock-in Alzheimer mouse models.

Accumulation of amyloid β-peptide (Aβ) is a driver of Alzheimer's disease (AD). Amyloid precursor protein (App) knock-in mouse models recapitulate AD-associated Aβ pathology, allowing elucidation of downstream effects of Aβ accumulation and their temporal appearance upon disease progression. Here we have investigated the sequential onset of AD-like pathologies in App and App knock-in mice by time-course transcriptome analysis of hippocampus, a region severely affected in AD.

Anlotinib plus icotinib as a potential treatment option for EGFR-mutated advanced non-squamous non-small cell lung cancer with concurrent mutations: final analysis of the prospective phase 2, multicenter ALTER-L004 study.

Background: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation and concurrent mutations have a poor prognosis. This study aimed to examine anlotinib plus icotinib as a first-line treatment option for advanced NSCLC carrying EGFR mutation with or without concurrent mutations.

Methods: This phase 2, single-arm, multicenter trial (ClinicalTrials.

Investigation and verification of GIMAP6 as a robust biomarker for prognosis and tumor immunity in lung adenocarcinoma.

Background And Aim: According to previous reports, GTPase of immunity-associated protein 6 (GIMAP6) is essential for autophagy. However, it is unclear how GIMAP6 affects the development and tumor immunity of lung adenocarcinoma (LUAD).

Methods: In the present study, the role of GIMAP6 in vivo and in vitro was examined using reverse transcription-quantitative PCR, western blotting, and Cell Counting Kit-8, colony formation and Transwell assays.

Hypothyroidism induced by immune checkpoint inhibitors combined with antiangiogenic agents is associated with higher body mass index.

Background: Recent studies have reported that the combination of immune checkpoint inhibitors (ICIs) and antiangiogenic agents could be a promising therapeutic strategy for advanced non-small cell lung cancer (NSCLC). However, both ICIs and antiangiogenic agents are associated with endocrine dysfunctions, mainly hypothyroidism. The risk of hypothyroidism is potentially increased with the combination of ICIs and antiangiogenic agents.

A novel pyroptosis-related prognostic signature for lung adenocarcinoma: Identification and multi-angle verification.

Lung adenocarcinoma (LUAD) is an aggressive disease of heterogeneous characteristics with poor prognosis and high mortality. Pyroptosis, a newly uncovered type of programmed cell death with an inflammatory nature, has been determined to hold substantial importance in the progression of tumors. Despite this, the knowledge about pyroptosis-related genes (PRGs) in LUAD is limited.

Bevacizumab/PD-1 inhibitor plus chemotherapy as first-line treatment of advanced non-squamous non-small-cell lung cancer.

To compare the effectiveness of PD-1 inhibitor or bevacizumab plus chemotherapy in advanced non-squamous non-small cell lung cancer (nsNSCLC). We retrospectively collected data for patients with advanced nsNSCLC who underwent first-line treatment with PD-1 inhibitor or bevacizumab plus chemotherapy (IC and BC groups). Propensity score matching (PSM) was adopted to balance covariates.

Identification of prognostic factors and nomogram model for patients with advanced lung cancer receiving immune checkpoint inhibitors.

Background And Aim: Some patients with lung cancer can benefit from immunotherapy, but the biomarkers that predict immunotherapy response were not well defined. Baseline characteristic of patients may be the most convenient and effective markers. Therefore, our study was designed to explore the association between baseline characteristics of patients with lung cancer and the efficacy of immunotherapy.

Metastatic pulmonary carcinoids with fusion response to ALK inhibitors: two case reports and review of literature.

Background: Pulmonary carcinoids (PC), including typical (TC) and atypical carcinoids (AC), are low-grade neuroendocrine tumors (NETs) which account for 1-5% of all lung tumors. Due to the low prevalence of PC and extreme rarity of anaplastic lymphoma kinase () rearrangements in patients with PC, the advances in targeted therapy development in PC are still limited and there is no standard treatment. Even though in patients with PC harboring rearrangements there is a room for a success in targeted therapy.

Increased CSF-decorin predicts brain pathological changes driven by Alzheimer's Aβ amyloidosis.

Cerebrospinal fluid (CSF) biomarkers play an important role in diagnosing Alzheimer's disease (AD) which is characterized by amyloid-β (Aβ) amyloidosis. Here, we used two App knock-in mouse models, App and App, exhibiting AD-like Aβ pathology to analyze how the brain pathologies translate to CSF proteomes by label-free mass spectrometry (MS). This identified several extracellular matrix (ECM) proteins as significantly altered in App knock-in mice.

Autophagy Impairment in Knock-in Alzheimer's Model Mice.

Alzheimer's disease (AD) is characterized by impaired protein homeostasis leading to amyloid-β peptide (Aβ) amyloidosis. Amyloid precursor protein (APP) knock-in mice exhibit robust Aβ pathology, providing possibilities to determine its effect on protein homeostasis including autophagy. Here we compared human AD postmortem brain tissue with brains from two different types of knock-in mice, and mice, exhibiting AD-like pathology.

Association of pre-existing lung interstitial changes with immune-related pneumonitis in patients with non-small lung cancer receiving immunotherapy.

Background And Aim: Many pieces of literature have evaluated the predictive value of pre-existing lung interstitial changes for immunotherapy-related pneumonia in patients with non-small cell lung cancer (NSCLC), but the results of studies are still controversial. The purpose of this article is to explore whether pre-existing lung interstitial changes can predict the occurrence of immunotherapy-related pneumonia.

Methods: PubMed, Web of Science, and Embase were used to search for relevant documents.