Language：Japanese   Publisher：Cancer Treatment and Research Communications  

Introduction: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare histologic type and is placed in the neuroendocrine tumor category along with small cell lung cancer (SCLC) at the latest histologic classification. Combination therapy with chemotherapy and immune checkpoint inhibitors is the standard of care for both non-small cell lung cancer and SCLC. However, the efficacy of immunochemotherapy for LCNEC has not yet been established. Methods and analysis: This prospective, multicenter, single-arm study will evaluate the efficacy of durvalumab plus carboplatin and etoposide in patients with advanced or relapsed LCNEC. Thirty patients were enrolled in this study. Patients will receive durvalumab intravenously combined with up to four cycles of carboplatin and etoposide, followed by durvalumab maintenance treatment. The primary endpoint is the objective response rate, and the key secondary endpoints are the duration of response, progression-free survival, overall survival, and safety. Conclusion: This is the prospective study to evaluate the efficacy of immunochemotherapy in patients with advanced or relapsed LCNEC. The results are expected to contribute to establishing the treatment strategy for LCNEC.

DOI： 10.1016/j.ctarc.2025.101008

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PubMed

Language：Japanese   Publisher：Clinical Lung Cancer  

Background: The PACIFIC trial established durvalumab administration after chemoradiotherapy as the standard of care for unresectable locally advanced nonsmall cell lung cancer (LA-NSCLC). However, the efficacy and safety of durvalumab in elderly patients aged 75 years or above remains unclear. This study aimed to investigate the real-world efficacy and safety of durvalumab for LA-NSCLC, with a specific focus on elderly patients. Patients and Methods: We reviewed 214 patients who received durvalumab out of 278 patients with unresectable LA-NSCLC who underwent chemoradiotherapy at 7 institutions between July 2018 and March 2022. Propensity score matching (PSM) analysis was performed to evaluate the efficacy of durvalumab in elderly patients. Results: The 2-year progression-free survival (PFS) and 2-year overall survival (OS) rates were 42.2% (95% confidence interval [CI], 34.7%-49.5%) and 77.1% (95% CI, 70.1-82.7%), respectively. Grade ≥ 3 immune-related adverse events (irAEs) occurred in 8.2% of patients. PSM analysis revealed that OS was significantly shorter in elderly patients (≥ 75 years) than in younger patients (< 75 years) (hazard ratio [HR]; 95% CI, 1.39-8.99; P = .008), whereas PFS did not differ significantly between the 2 groups (HR: 1.50, 95% CI, 0.84-2.68, P = .169). The frequency of irAEs did not differ between these groups. Conclusions: The real-world efficacy and safety of durvalumab administration following chemoradiotherapy for LA-NSCLC coincided with the PACIFIC trial's findings. Disease control achieved with this protocol did not differ significantly between elderly and younger patients but had acceptable tolerability, demonstrating its benefit even in elderly LA-NSCLC patients aged 75 years or above.

DOI： 10.1016/j.cllc.2024.07.001

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PubMed

Language：Japanese   Publisher：Cancers  

Analyses of our microRNA (miRNA) expression signature combined with The Cancer Genome Atlas (TCGA) data revealed that both strands of pre-miR-139 (miR-139-5p, the guide strand, and miR-139-3p, the passenger strand) are significantly downregulated in lung adenocarcinoma (LUAD) clinical specimens. Functional analyses of LUAD cells ectopically expressing miR-139-3p showed significant suppression of their aggressiveness (e.g., cancer cell proliferation, migration, and invasion). The involvement of the passenger strand, miR-139-3p, in LUAD pathogenesis, is an interesting finding contributing to the elucidation of unknown molecular networks in LUAD. Of 1108 genes identified as miR-139-3p targets in LUAD cells, 21 were significantly upregulated in LUAD tissues according to TCGA analysis, and their high expression negatively affected the prognosis of LUAD patients. We focused on thyroid hormone receptor interactor 13 (TRIP13) and investigated its cancer-promoting functions in LUAD cells. Luciferase assays showed that miR-139-3p directly regulated TRIP13. siRNA-mediated TRIP13 knockdown and TRIP13 inhibition by a specific inhibitor (DCZ0415) attenuated the malignant transformation of LUAD cells. Interestingly, when used in combination with anticancer drugs (cisplatin and carboplatin), DCZ0415 exerted synergistic effects on cell proliferation suppression. Identifying the molecular pathways regulated by tumor-suppressive miRNAs (including passenger strands) may aid in the discovery of diagnostic markers and therapeutic targets for LUAD.

DOI： 10.3390/cancers15235571

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PubMed

Language：Japanese   Publisher：FEBS Open Bio  

Lung cancer is the most common cause of cancer-related death worldwide, accounting for 1.8 million deaths annually. Analysis of The Cancer Genome Atlas data showed that all members of the minichromosome maintenance (MCM) family (hexamers involved in DNA replication: MCM2-MCM7) were upregulated in lung adenocarcinoma (LUAD) tissues. High expression of MCM4 (P = 0.0032), MCM5 (P = 0.0032), and MCM7 (P = 0.0110) significantly predicted 5-year survival rates in patients with LUAD. Simurosertib (TAK-931) significantly suppressed the proliferation of LUAD cells by inhibiting cell division cycle 7-mediated MCM2 phosphorylation. This finding suggested that MCM2 might be a therapeutic target for LUAD. Moreover, analysis of the epigenetic regulation of MCM2 showed that miR-139-3p, miR-378a-5p, and miR-2110 modulated MCM2 expression in LUAD cells. In patients with LUAD, understanding the role of these miRNAs may improve prognoses.

DOI： 10.1002/2211-5463.13681

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PubMed

Language：Japanese   Publisher：Molecular Oncology  

Small-cell lung cancer (SCLC) is associated with a high mortality rate and limited treatment efficacy. We created a microRNA (miRNA) expression signature by RNA sequencing using specimens from patients with SCLC who had failed treatment. Forty-nine miRNAs were downregulated in SCLC tissues and were candidate tumor-suppressive miRNAs. In this signature, both guide and passenger strands were downregulated for five miRNAs (miR-30a, miR-34b, miR-34c, miR-223, and miR-4529). Recent studies have revealed that passenger strands of miRNAs are involved in the molecular pathogenesis of human cancer. Although miR-30a-5p (the guide strand) has been shown to be a tumor-suppressive miRNA in various types of cancers, miR-30a-3p (the passenger strand) function is not well characterized in SCLC cells. We investigated the functional significance of miR-30a-3p and oncogenic genes regulated by miR-30a-3p in SCLC cells. Ectopic expression assays showed that miR-30a-3p expression inhibited cell proliferation and induced cell cycle arrest and apoptosis in two SCLC cell lines. Furthermore, in silico database searches and gene expression assays identified 25 genes as putative targets of miR-30a-3p in SCLC cells. Luciferase reporter assays revealed that downstream neighbor of SON (DONSON) was directly regulated by miR-30a-3p in SCLC cells. Knockdown of DONSON induced cell cycle arrest in SCLC cells and DONSON overexpression were detected in SCLC clinical samples. Analyzing the regulatory networks of tumor-suppressive miRNAs may lead to the identification of therapeutic targets in SCLC.

DOI： 10.1002/1878-0261.13339

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PubMed

Language：Japanese   Publisher：(一社)日本結核・非結核性抗酸菌症学会  

症例は25歳女性。右眼の見えにくさを主訴に当院眼科を受診し,蛍光眼底検査で結核性ぶどう膜炎を疑われた。インターフェロンガンマ遊離試験(Interferon-gamma release assay:IGRA)が陽性であり,胸部単純X線検査で右上肺野に粒状影を認め,体幹部CTで右肺上葉S2に小葉中心性の粒状影と浸潤影を,左肺上葉にもわずかに粒状影を認めた。喀痰抗酸菌検査は陰性であり,経気管支生検でラングハンス型多核巨細胞を伴う壊死性肉芽腫を認めた。画像所見,IGRA陽性およびその他の検査結果とあわせて,肺結核および結核性ぶどう膜炎と診断した。抗結核薬の標準治療(イソニアジド,リファンピシン,エタンブトール,ピラジナミド)を開始し,治療2ヵ月後のCTで両側肺野の粒状影,浸潤影は消退傾向であった。右眼の症状については,経過中に硝子体出血を合併したため,硝子体手術を施行し,症状は回復した。結核性ぶどう膜炎は診断の遅れが失明につながる可能性がある。そのため,眼科と密な連携をとり,早期診断,早期治療介入を行う必要がある。(著者抄録)

Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

Language：Japanese   Publisher：Biomedicines  

Several recent studies have shown that both strands of certain miRNAs derived from miRNA duplexes are involved in cancer pathogenesis. Our own recent studies revealed that both strands of the miR-150 duplex act as tumor-suppressive miRNAs in lung adenocarcinoma (LUAD) through the targeting of several oncogenes. The aim of the study here was to further investigate the tumor-suppressive roles of miR-150-3p (the passenger strand) in lung squamous cell carcinoma (LUSQ) and its control of cancer-promoting genes in LUSQ cells. The downregulation of miR-150-3p in LUSQ tissues was confirmed by data in The Cancer Genome Atlas (TCGA). The ectopic expression of miR-150-3p attenuated cancer cell aggressive features, e.g., cell cycle arrest, migration and invasive abilities. Our target search strategy successfully identified a total of 49 putative targets that were listed as subjects of miR-150-3p regulation in LUSQ cells. Interestingly, among these targets, 17 genes were categorized as related to the “cell cycle” based on Gene Ontology (GO) classification, namely CENPA, CIT, CCNE1, CCNE2, TIMELESS, BUB1, MCM4, HELLS, SKA3, CDCA2, FANCD2, NUF2, E2F2, SUV39H2, CASC5, ZWILCH and CKAP2). Moreover, we show that the expression of HELLS (helicase, lymphoid specific) is directly controlled by miR-150-3p, and its expression promotes the malignant phenotype of LUSQ cells.

DOI： 10.3390/biomedicines9121883

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PubMed

Language：Japanese   Publisher：The Japan Society for Respiratory Endoscopy  

<p><b><i>Background.</i></b> Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe and useful procedure for the diagnosis of mediastinal lymphadenopathy, and procedure-related complications are uncommon. We report a case of endotracheal mass formation at the intratracheal puncture site after EBUS-TBNA. <b><i>Case.</i></b> A 76-year-old man presented with a productive cough. Chest computed tomography (CT) revealed a mass in the right upper lobe and mediastinal lymphadenopathy; we suspected primary lung cancer and metastatic mediastinal lymphadenopathy. He underwent EBUS-TBNA for the mediastinal lymphadenopathy and was diagnosed with mediastinal lymph node metastasis; however, it was difficult to determine the tissue type in detail. Forty days later, we attempted to perform bronchoscopy again and detected endotracheal mass formation at the puncture site. An endotracheal biopsy specimen was obtained from the mass, and a histopathological examination revealed non-small cell carcinoma -- not otherwise specified. Immune checkpoint inhibitor treatment was initiated, and the endotracheal mass lesion resolved during follow-up. <b><i>Conclusion.</i></b> We should pay attention to the possibility of tumor growth at the site of EBUS-TBNA in cases of metastatic lymphadenopathy.</p>

DOI： 10.18907/jjsre.43.6_608

CiNii Research

Language：Japanese   Publisher：(一社)日本呼吸器内視鏡学会  

背景.超音波気管支鏡ガイド下針生検(endobronchial ultrasound-guided transbronchial needle aspiration:EBUS-TBNA)は,縦隔リンパ節病変の診断において安全で有用な検査であり,手技に伴う合併症は少ない.EBUS-TBNA後に穿刺部位に腫瘤性病変が出現した症例を経験したため報告する.症例.76歳男性.湿性咳嗽を主訴に受診し胸部CT検査で右肺上葉の腫瘤影と縦隔リンパ節腫大を認め,原発性肺癌,縦隔リンパ節転移が疑われた.縦隔リンパ節に対しEBUS-TBNAを行いリンパ節転移の診断となったが,詳細な組織型の判定が困難であった.40日後に再度気管支鏡検査を施行したところ,前回の穿刺部位から気管内に腫瘤性病変が出現しており,同部位からの生検で非小細胞肺癌(not otherwise specified:NOS)の診断となった.免疫チェックポイント阻害薬による治療を行ったところ,気管内病変の改善を認めた.結論.縦隔リンパ節転移病変において,EBUS-TBNAの穿刺手技により病変の気管内進展を来す可能性があり注意が必要である.(著者抄録)

Language：Japanese   Publisher：Cancers  

Small cell lung cancer (SCLC) is a highly aggressive cancer, and patients who become refractory to first-line treatment have a poor prognosis. The development of effective treatment regimens is urgently needed. In this study, we identified a gene expression signature of SCLC after treatment failure using SCLC clinical specimens (GEO accession number: GSE162102). A total of 1,136 genes were significantly upregulated in SCLC tissues. These upregulated genes were subjected to KEGG pathway analysis, and “cell cycle”, “Fanconi anemia”, “alcoholism”, “systemic lupus erythematosus”, “oocyte meiosis”, “homologous recombination”, “DNA replication”, and “p53 signaling” were identified as the enriched pathways among the genes. We focused on the cell cycle pathway and investigated the clinical significance of four genes associated with this pathway: minichromosome maintenance (MCM) 2, MCM4, MCM6, and MCM7. The overexpression of these MCM genes was confirmed in SCLC clinical specimens. Knockdown assays using siRNAs targeting each of these four MCM genes showed significant attenuation of cancer cell proliferation. Moreover, siRNA-mediated knockdown of each MCM gene enhanced the cisplatin sensitivity of SCLC cells. Our SCLC molecular signature based on SCLC clinical specimens after treatment failure will provide useful information to identify novel molecular targets for this disease.

DOI： 10.3390/cancers13061187

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PubMed

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese