High-throughput virtual screening to identify potential small molecule inhibitors of the Zα domain of the adenosine deaminases acting on RNA 1(ADAR1).

Changes in RNA editing are closely associated with diseases such as cancer, viral infections, and autoimmune disorders. Adenosine deaminase (ADAR1), which acts on RNA 1, plays a key role in adenosine to inosine editing and is a potential therapeutic target for these various diseases. The p150 subtype of ADAR1 is the only one that contains a Zα domain that binds to both Z-DNA and Z-RNA.

Comparative analysis of genomic profiles between tissue-based and plasma-based next-generation sequencing in patients with non-small cell lung cancer.

Objectives: Genotype-guided personalized therapy has become an essential part of routine clinical care in non-small cell lung cancer (NSCLC) patients. However, small tissue specimens often yield inadequate molecular testing material. Plasma ctDNA-based liquid biopsy is an increasingly common non-invasive alternative to tissue biopsy.

Laboratory blood test profiling reveals distinct biochemical and hemocyte features of mutated non-small cell lung cancer.

Background: The testing for capability of some routine blood test parameters to reflect the biology of non-small cell lung carcinoma with different driver mutations is of great interest and practice significance. We aim to screen these variables and, if allowed, develop a novel predictive model based on results of these routine blood tests commonly performed in clinical practice to inform which can help doctors assess the patient's genetic mutation status as early as possible before surgery.

Methods: For the exploration cohort, we included 1,595 patients who were diagnosed with non-small cell lung cancer (NSCLC) and genetically profiled by a next-generation sequencing panel in the First Affiliated Hospital of Guangzhou Medical University.

Cell pellet from fixative medium of transbronchial lung biopsy sample improves lung cancer ancillary test.

Objectives: Lung cancer tissue obtained using small biopsies are relatively fragile, leaving behind some tiny tissue fragments or cell clusters in the fixative medium that are difficult to collect for processing as a paraffin-embedded tissue block. Usually, the cellular component of the residual fixative medium is discarded as medical waste as per routine laboratory protocol. No protocol exists for utilizing the cellular component of the residual fixative medium after processing the tissue blocks to improve lung cancer ancillary testing.

Efficacy of Intrapleural or Intrapericardial Injection of Single Bevacizumab in the Treatment of Lung Cancer-Mediated Malignant Effusion.

The usage of bevacizumab for malignant pleural effusion (MPE) or malignant pericardial effusion (MPCE) has attracted increasing interest from researchers, but the precise ways of bevacizumab administration remain unknown. Patients with histologically or cytologically confirmed non-small-cell lung cancer (NSCLC) with MPE or MPCE were enrolled in the study and treated with a low dose of single bevacizumab (100 mg) intrapleurally or intrapericardially injected after the drainage of the effusions. The Lung Cancer Symptom Scale (LCSS), efficacy, and safety of drug administration were used as evaluation parameters in this study.

Intratumor heterogeneity of driver mutations and TMB distribution in 30 early-stage LUAD patients with multiple lesions.

Background: Differentiating multiple pulmonary lesions as multiple primary lung cancer (MLC) or intra-pulmonary metastasis (IPM) is critical. Lung cancer also has a high genetic heterogeneity, which influenced the treatment strategy. Genetic information may aid in tracing lineage information on multiple lung lesions.

miR-29b Regulates Lung Cancer Progression by Downregulating FEM1B and Inhibiting the FOX01/AKT Pathway.

Purpose: Lung cancer is a relatively common type of cancer, and the incidence rate has been on the rise in recent years. MicroRNAs are a class of endogenous small RNA molecules, which are essential for the posttranscriptional regulation of genes. miR-29b is closely related to the occurrence and development of tumors, including prostate cancer, colon cancer, and breast cancer.

High Tumor Mutation Burden and DNA Repair Gene Mutations are Associated with Primary Resistance to Crizotinib in -Rearranged Lung Cancer.

Background: About 20% of patients with -rearranged non-small cell lung cancer (NSCLC) develop acquired resistance to tyrosine kinase inhibitor (TKI) during the first 6 months. This study aimed to examine the molecular mechanisms of early TKI resistance and prognosis in -rearranged NSCLC.

Methods: Ten patients with -rearranged NSCLC were included: five who developed rapid resistance to crizotinib (progression-free survival (PFS) ≤3 months) and five who exhibited a good response to crizotinib (PFS ≥36 months).

Unraveling the Novel Effect of Patchouli Alcohol Against the Antibiotic Resistance of .

The long-term colonization of can cause various gastrointestinal diseases, and its high genetic variability is prone to antibiotic resistance and leads to failure of clinical treatment. Intracellular survival also contributes to the drug tolerance of . Patchouli alcohol (PA) shows a highly efficient activity against and .

Effects of nursing based on Orem's self-care model on self-care efficacy, quality of life and adverse emotions in patients with advanced lung cancer.

Objective: To investigate the effects of nursing based on Orem's self-care model on self-care efficacy, quality of life (QOL) and adverse emotions of patients with advanced lung cancer (ALC) receiving chemotherapy.

Methods: A total of 71 patients with ALC aged 50-70 years, from our hospital were selected as the study subjects and divided into the control group (CNG, n = 35) and the experimental group (EXG, n = 36) using the random number table method. The CNG was treated with conventional chemotherapy combined with conventional nursing, while the EXG was treated with conventional chemotherapy combined with nursing based on Orem's self-care model.

Integrating Histologic and Genomic Characteristics to Predict Tumor Mutation Burden of Early-Stage Non-Small-Cell Lung Cancer.

Tumor mutation burden (TMB) serves as an effective biomarker predicting efficacy of mono-immunotherapy for non-small cell lung cancer (NSCLC). Establishing a precise TMB predicting model is essential to select which populations are likely to respond to immunotherapy or prognosis and to maximize the benefits of treatment. In this study, available Formalin-fixed paraffin embedded tumor tissues were collected from 499 patients with NSCLC.

Clinical Strains of With Strong Cell Invasiveness and the Protective Effect of Patchouli Alcohol by Improving miR-30b/C Mediated Xenophagy.

was classified by the World Health Organization as a class 1 carcinogen. The development of drug-resistant strains of this pathogen poses a serious threat to human health worldwide. The cell invasion of activates xenophagy in gastric epithelial cells by mediating miR-30b/c, and the emergence of autophagosomes provides a niche that enables the survival of intracellular and promotes its drug resistance.

A study on different therapies and prognosis-related factors for brain metastases in lung adenocarcinoma patients with driver mutation.

Brain metastases (BMs) are frequently occurred in lung adenocarcinoma with driver mutation. There is a need to explore multi-discipline treatments and prognostic factors in those patients with most frequent driver mutations: EGFR mutation and ALK fusion. In the retrospective study, different therapies and prognostic factors were compared between EGFR and ALK-driven lung adenocarcinoma with BMs.

Genetic alteration profile of -mutant resected IIB-IIIA stage NSCLC and correlation to clinical outcomes.

Background: Genetic alteration profile of epidermal growth factor receptor () mutant resected non-small cell lung cancer (NSCLC) and its relationship with clinical outcomes remains to be illustrated and genetic biomarkers that can predict recurrence need to be figured out.

Methods: Clinicopathological and follow-up information were collected for 99 -mutant resected NSCLC. Tumor sections were collected for genetic alteration detection.

The characterization of lung microbiome in lung cancer patients with different clinicopathology.

There were few knowledge concerned correlation between lung microbiome and different clinicopathology of lung cancer. Bronchial washing fluid (BWF) and sputum are commonly used sample types but there was no study comparing difference of microbiome between these two in lung cancer. In this study, we aimed to compare difference of microbiome between these two sample types and characterize lung microbiome in squamous cell lung carcinoma with (SCC_M1) or without distant metastasis (SCC_M0) and lung adenocarcinoma with (AD_M1) or without distant metastasis (AD_M0).

Predictive and prognostic value of phosphorylated c-KIT and PDGFRA in advanced non-small cell lung cancer harboring ALK fusion.

Secondary gene amplification leads to tyrosine kinase inhibitor resistance in anaplastic lymphoma kinase (ALK) fusion-positive advanced non-small cell lung cancer (NSCLC). The presence of the 4q12 amplicon causes the activation of downstream mast/stem cell growth factor receptor Kit (c-Kit) or platelet-derived growth factor receptor α (PDGFRA) signaling pathways. Therefore, in the present study, the association between the functional proteins phosphorylated c-Kit (p-c-Kit) and phosphorylated PDGFRA (p-PDGFRA) and the prognosis of ALK fusion NSCLC was investigated.

RAGE mediates β-catenin stabilization via activation of the Src/p-Cav-1 axis in a chemical-induced asthma model.

We previously demonstrated receptor for advanced glycation end products (RAGE) was required for β-catenin stabilization in a toluene diisocyanate (TDI)-induced asthma model, suggesting it plays an important role in TDI-induced airway inflammation. The aim of this study was to examine whether RAGE mediates β-catenin stabilization via activation of the Src/p-Cav-1 axis in TDI-induced asthma model. To generate a chemical-induced asthma model, male BALB/c mice were sensitized and challenged with TDI.

Establishment of peripheral blood mononuclear cell-derived humanized lung cancer mouse models for studying efficacy of PD-L1/PD-1 targeted immunotherapy.

Animal models used to evaluate efficacies of immune checkpoint inhibitors are insufficient or inaccurate. We thus examined two xenograft models used for this purpose, with the aim of optimizing them. One method involves the use of peripheral blood mononuclear cells and cell line-derived xenografts (PBMCs-CDX model).

Next generation sequencing-based molecular profiling of lung adenocarcinoma using pleural effusion specimens.

Background: Molecular profiling of non-small cell lung cancer (NSCLC) is essential for therapeutic decision-making. Pleural effusion obtained by a non-invasive, repeatable procedure may provide an opportunity for molecular profiling and thereby possibly provide information enabling targeted therapy. In this study, we aimed to evaluate the diagnostic performance of pleural effusion as a specimen for molecular analysis.

Comprehensive targeted super-deep next generation sequencing enhances differential diagnosis of solitary pulmonary nodules.

Background: A non-invasive method to predict the malignancy of surgery-candidate solitary pulmonary nodules (SPN) is urgently needed.

Methods: Super-depth next generation sequencing (NGS) of 35 paired tissues and plasma DNA was performed as an attempt to develop an early diagnosis approach.

Results: Only ~6% of malignant nodule patients had driver mutations in the circulating tumour DNA (ctDNA) with >10,000-fold sequencing depth, and the concordance of mutation between tDNA and ctDNA was 3.

Defined, serum/feeder-free conditions for expansion and drug screening of primary B-acute lymphoblastic leukemia.

Functional screening for compounds represents a major hurdle in the development of rational therapeutics for B-acute lymphoblastic leukemia (B-ALL). In addition, using cell lines as valid models for evaluating responses to novel drug therapies raises serious concerns, as cell lines are prone to genotypic/phenotypic drift and loss of heterogeneity . Here, we reported that OP9 cells, not OP9-derived adipocytes (OP9TA), support the growth of primary B-ALL cells .

Development and clinical validation of a circulating tumor DNA test for the identification of clinically actionable mutations in nonsmall cell lung cancer.

Molecular analysis of potentially actionable mutations has become routine practice in oncological pathology. However, testing a wide range of oncogenes and mutations can be technically challenging because of limitations associated with tumor biopsy. Circulating tumor DNA (ctDNA) is a potential tool for the noninvasive profiling of tumors.

CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression.

Interleukin 15 (IL-15) regulates the development, survival, and functions of multiple innate and adaptive immune cells and plays a dual role in promoting both tumor cell growth and antitumor immunity. Here, we demonstrated that the injection of recombinant human IL-15 (200 µg/kg) or murine IL-15 (3 µg/kg) to tumor-bearing NOD- (NSI) mice resulted in increased tumor progression and CD45+ CD11b+ Gr-1+ CD215+ cell expansion in the tumors and spleen. In B16F10-bearing C57BL/6 mice model, we found that murine IL-15 has antitumoral effect since the activation and expansion of CD8+ T cells with murine IL-15 treatment.

Erlotinib intercalating pemetrexed/cisplatin versus erlotinib alone in Chinese patients with brain metastases from lung adenocarcinoma: a prospective, non-randomised, concurrent controlled trial (NCT01578668).

Objective: Erlotinib has a synergistic effect with pemetrexed for treating non-squamous non-small-cell lung cancer. We investigated the efficacy and safety of erlotinib (E) in combination with pemetrexed/cisplatin (E-P) in Chinese patients with lung adenocarcinoma with brain metastases.

Design: Patients who were erlotinib-naïve or pemetrexed-naïve were assigned in parallel to receive either E or E-P.