Background: Postoperative adjuvant systemic therapy with atezolizumab for lung cancer has been reported to be effective. Although myocarditis is a rare immune adverse event associated with atezolizumab, it can have a serious course and should be treated with caution. We herein report a case of fulminant myocarditis during adjuvant systemic therapy with atezolizumab. Case presentation: The patient was a 49-year-old Asian woman. She was diagnosed with pT2aN1M0 stage IIB (Programmed Death Ligand 1(PD-L1), 50%) after surgery for right upper lobe lung adenocarcinoma. Atezolizumab was administered following platinum-based adjuvant chemotherapy. On day 14, the patient was hospitalized because of deterioration in her general condition caused by fever. On day 16, she developed dyspnea, which worsened, and on day 17, she experienced shock. Blood tests, echocardiography, and cardiac catheterization were performed, and the patient was diagnosed with cardiogenic shock due to myocarditis. Initial measures did not improve the patient’s shock state. The patient was transferred to hospital for the use of an assistive circulatory system. Pulse steroid therapy was administered, and myocarditis showed a tendency toward improvement. A retrospective review of the patient’s history revealed a decreased lymphocyte count and an increase in the neutrophil/lymphocyte ratio, which may be useful for detecting severe immune-related adverse events. The troponin levels were elevated, but creatine phosphokinase level remained within the normal range. Conclusion: Myocarditis can be fatal due to the rapid progression of symptoms. Close follow-up, a prompt diagnosis, and therapeutic intervention are important. Decreased lymphocyte counts, increased neutrophil/lymphocyte ratios, and the measurement of multiple myocardial biomarkers are considered useful for the early diagnosis of myocarditis.

Objectives: The recent increase in sublobar resections has been driven by favourable long-term outcomes and advances in stapling devices. However, maintaining an adequate resection margin remains a critical oncological requirement. This study aimed to investigate whether deep wedge resection induces subpleural alveolar injury that could lead to margin overestimation by creating undetectable internal cavities. Methods: We retrospectively analysed 33 consecutive patients who underwent wedge resection and CT imaging of resected lung specimens between December 2018 and February 2025. CT was performed on inflated specimens to better visualize internal lung architecture. We assessed the presence of an “empty space” adjacent to the staple line and correlated it with clinical factors, including depth of wedge resection (WR). Additionally, ex vivo porcine lung models were used to simulate deep WR, analyse compression effects, and identify histological damage caused by stapler compression. Results: CT imaging revealed empty spaces adjacent to the staple line in 10 of 33 specimens (30.3%), with a mean cavity length of 8.25 ± 3.2 mm. This artifact was significantly associated with deeper WR (≥26.3 mm) and increased stapler cartridge usage (median: 4 vs 3, P = .0298). In porcine experiments, compression to 2 mm thickness resulted in internal parenchymal rupture without pleural tearing, replicating the clinical findings. Conclusions: This study identified a potential mechanism by which deep wedge resection may lead to overestimation of the pathological margin due to stapler-induced parenchymal rupture. Further large-scale studies integrating oncological outcomes are warranted to clarify how wedge resection and segmentectomy should be appropriately selected for deep peripheral lung lesions.

Approximately half of Japanese patients with lung adenocarcinoma (LUAD) have epi-dermal growth factor receptor (EGFR) gene mutations. Therefore, EGFR is the most critical therapeutic target in treating LUAD. This study’s purpose is to explore novel therapeutic targets for LUAD and further improve EGFR inhibitor combination therapy. We created microRNA (miRNA) expression signatures from clinical specimens of LUAD patients harboring EGFR gene mutations using RNA sequencing. Based on the miRNA signature, we focused on miR-206, which had the most downregulated expression. We searched for its target gene in LUAD cells by facilitating transfection of miR-206 into the EGFR mutant cell line PC9 and searching for genes with suppressed expression. A total of 821 genes were downregulated in PC9 cells. Through molecular classification of these genes, we revealed that 18 genes were closely related to the cell cycle. Among these genes, we focused on cyclin-dependent kinase 4 (CDK4) and investigated the synergistic effects of a CDK4/6 inhibitor (abemaciclib or palbociclib) and osimertinib, an EGFR inhibitor in LUAD cells. In vitro and three-dimensional culture analyses showed that combination therapy with a CDK4/6 inhibitor and an EGFR inhibitor synergistically suppressed proliferation of LUAD cells with EGFR mutations. Our miRNA-based analysis is an excellent strategy for identifying therapeutic targets for LUAD. Continued analysis will reveal target molecules that enhance the therapeutic effects of EGFR inhibitors.

Estrogen receptor (ER)-positive breast cancer (BrCa) accounts for two-thirds of all BrCa cases worldwide. Therefore, ER-targeted endocrine therapy is the standard treatment for this disease. There has been a recent trend towards developing combination therapies using molecularly targeted drugs to improve outcomes. This study aimed to identify therapeutic targets demonstrating efficacy when combined with fulvestrant (a selective ER downregulator/degrader). We generated microRNA (miRNA) signatures from fulvestrant-treated MCF-7 cells by RNA sequencing. From the signature, we evaluated miR-374b-5p because its expression was elevated by fulvestrant treatment in MCF-7 cells. Also, in expression analysis by subtype of BrCa patients, miR-374b-5p expression was suppressed only in luminal BrCa. Ectopic expression assays revealed that miR-374b-5p attenuated the malignant phenotypes of MCF-7 cells. We searched for genes regulated by miR-374b-5p and discovered that 11 (NEK2, NUF2, HMMR, DEPDC1B, FOXM1, ELOVL6, KIF20A, NCAPH, CENPK, FAM83D, and KIAA0101) are closely involved in BrCa molecular pathogenesis. Among these target genes, we focused on forkhead box M1 (FOXM1), a transcription factor regulating cell cycle progression and division. Notably, combination therapy with fulvestrant and a FOXM1 inhibitor significantly suppressed MCF-7 cell proliferation. From the miRNA signature established in this study, we identified antitumor miR-374b-5p and its target genes and used these findings to explore candidate drugs with potential efficacy when combined with fulvestrant.

Background/Objective: An analysis of microRNA (miRNA) expression signatures in lung adenocarcinoma (LUAD) harboring EGFR mutations revealed that multiple miRNAs, including miR-126-3p, were suppressed in cancer tissues. This study focused on miR-126-3p and aimed to identify therapeutic target genes regulated by miR-126-3p in LUAD harboring EGFR mutations and evaluate their potential for combination therapy with EGFR tyrosine kinase inhibitors. Methods: The antitumor function of miR-126-3p was analyzed by the ectopic expression of miR-126-3p into LUAD cells with EGFR mutation. The target genes of miR-126-3p were identified through an analysis of the TargetScan, Genecodis 4 and TCGA databases. The Chou–Talalay method was used to determine the potential synergistic effects of selected drug combinations. Results: The expression of miR-126-3p attenuated the malignant transformation of LUAD cells through targeting the “EGFR tyrosine kinase inhibitor resistance pathway”. We focused on AKT2 among the genes involved in this pathway. Capivasertib was recently approved as the first inhibitor of oncogenic AKT signaling. Therefore, we investigated the effect of combination therapy comprising osimertinib and capivasertib on LUAD cell viability. Combination therapy synergistically reduced cell viability in both PC9 and H1975 cells, with combination index values of 0.61 and 0.14, respectively, at Fa = 0.5. Conclusions: Our miRNA-based analysis is an excellent strategy for identifying therapeutic targets that enhance the effects of EGFR inhibitors on LUAD.