Clinical Relevance of Patient-Derived Organoid of Surgically Resected Lung Cancer as an In Vitro Model for Biomarker and Drug Testing.

Introduction: Lung tumor organoids (LTOs) have attracted attention as preclinical models; however, their clinical and experimental applications have not been fully established.

Methods: We attempted to establish LTOs from resected specimens of patients with lung cancer who underwent lung resection. Clinicopathologic characteristics related to the establishment of LTOs were evaluated.

Secondary Mutations of the EGFR Gene That Confer Resistance to Mobocertinib in EGFR Exon 20 Insertion.

Introduction: Approximately 10% of mutations in the EGFR gene in NSCLC are in-frame insertions in exon 20 (X20ins). These tumors usually do not respond to conventional EGFR tyrosine kinase inhibitors (TKIs). Several novel EGFR TKIs active for X20ins are in clinical development, including mobocertinib, which was recently approved by the U.

Recontact: a survey of current practices and BRCA1/2 testing in Japan.

Genetic testing advances have enabled the provision of previously unavailable information on the pathogenicity of genetic variants, frequently necessitating the recontact of former patients by clinicians. In Japan, national health insurance coverage was extended to BRCA1/2 testing for the diagnosis of hereditary breast and ovarian cancer for patients who meet certain criteria in 2020, and conditions necessitating recontact were expected to increase. Studies and discussions regarding recontact have been conducted in the U.

Inter- and Intratumor Heterogeneity of EGFR Compound Mutations in Non-Small Cell Lung Cancers: Analysis of Five Cases.

Background: Several clinical and preclinical studies suggest that non-small cell lung cancers (NSCLCs) with EGFR compound mutations were associated with lower efficacies of first-generation EGFR inhibitors than tumors with single EGFR mutation. Some researchers hypothesize that EGFR mutation status is heterogeneous in such tumors and that second-generation EGFR inhibitors may eliminate cancer cells with uncommon EGFR mutations from tumors with EGFR compound mutations. However, this hypothesis is currently unproven; therefore, we performed the current study to determine if tumor cells with EGFR compound mutations are present in heterogeneous or homogeneous manners.

Spatial heterogeneity of acquired resistance mechanisms to 1st/2nd generation EGFR tyrosine kinase inhibitors in lung cancer.

Background: Overcoming acquired resistance against targeted therapies to improve outcomes of lung cancer patients harboring driver mutations is a critical issue. While drug therapy oriented to a resistance mechanism appears attractive, spatial heterogeneity of resistance mechanisms in each patient will diminish treatment efficacy. However, the frequency, clinical backgrounds, clinical implications, and patterns of spatial heterogeneity in resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs) are largely unknown.

Semiautomated Segmentation and Measurement of Cytoplasmic Vacuoles in a Neutrophil With General-Purpose Image Analysis Software.

Background: Morphological observation of blood or marrow film is still described nonquantitatively. We developed a semiautomatic method for segmenting vacuoles from the cytoplasm using Photoshop (PS) and Image-J (IJ), called PS-IJ, and measured the relative entire cell area (rECA) and relative areas of vacuoles (rAV) in the cytoplasm of neutrophil with PS-IJ.

Methods: Whole-blood samples were stored at 4°C with ethylenediaminetetraacetate and in two different preserving manners (P1 and P2).

Fusion protein of retinoic acid receptor alpha with promyelocytic leukemia protein or promyelocytic leukemia zinc finger protein recruits N-CoR-TBLR1 corepressor complex to repress transcription in vivo.

Fusion proteins of retinoic acid receptor alpha (RARalpha) with promyelocytic leukemia protein (PML-RARalpha) or with promyelocytic leukemia zinc finger protein (PLZF-RARalpha) are associated with and likely responsible for the development of acute promyelocytic leukemia. These oncoproteins retain the ability to bind DNA and retinoic acid through the RARalpha moiety. This enables them to repress RARalpha target genes in the absence of retinoic acid, but the underlying mechanisms remain to be investigated.