Language：English  

DOI： 10.1002/rcr2.1392

PubMed

Language：English  

DOI： 10.5761/atcs.oa.23-00134

PubMed

Language：English  

A 75-year-old woman presented at our hospital with bilateral visual impairment. Ophthalmological examination revealed multiple choroidal tumours. Chest computed tomography revealed a tumour shadow in the right lower lobe and multiple lymph node metastases in the mediastinum and pulmonary hilum. Following a detailed examination, the patient was diagnosed with primary lung adenocarcinoma (cT1cN3M1c Stage IVB) with choroid metastases. The tumour proportion score of programmed death ligand 1 (PD-L1) was 1% and EGFR exon 20 insertion mutations were also detected. The patient was administered combination chemotherapy with nivolumab and ipilimumab. Primary lung and metastatic tumours, including the choroid, were reduced, and visual disturbances improved completely. Herein, we describe a rare case in which a combination of chemotherapy with nivolumab and ipilimumab significantly reduced vision loss due to choroidal metastasis.

DOI： 10.1002/rcr2.1262

PubMed

Language：Japanese   Publisher：(一社)日本呼吸器学会  

症例は66歳,男性.発熱と右胸水貯留の精査目的で,当科に紹介入院となった.CRP上昇と血小板減少,プロカルシトニン陽性,腎障害を認めた.組織球主体の滲出性胸水であり,播種性血管内凝固(disseminated intravascular coagulation:DIC)を合併し,抗菌薬不応性であった.頸部・腋窩・腹部傍大動脈リンパ節の軽度腫大,腎障害,胸腹水および全身浮腫の悪化があり,骨髄生検で細網線維化と巨核球増多を認め,TAFRO症候群と診断した.原因不明の胸膜炎を認める例では鑑別診断にTAFRO症候群を考慮する必要がある.(著者抄録)

Language：English  

DOI： 10.1016/j.rmcr.2024.102037

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

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

PubMed

Language：English  

DOI： 10.1016/j.resinv.2023.09.006

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

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

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The involvement of passenger strands of miRNAs in the molecular pathogenesis of human cancers is a recent concept in miRNA research, and it will broaden our understanding of the molecular mechanisms of miRNA-mediated cancer. The analysis of our miRNA signature of LUAD revealed that both strands of pre-miR-486 (miR-486-5p and miR-486-3p) were downregulated in LUAD tissues. Ectopic expression of both miRNAs induced cell cycle arrest in LUAD cells, suggesting both strands of miRNAs derived from pre-miR-486 were tumor suppressive. Our in silico analysis showed a total of 99 genes may be under the control of both miRNAs in LUAD cells. Importantly, among these targets, the high expression of seven genes (MKI67, GINS4, RRM2, HELLS, MELK, TIMELESS, and SAPCD2) predicted a poorer prognosis of LUAD patients (p < 0.05). We focused on GINS4, a DNA replication complex GINS protein that plays an essential role in the initiation of DNA replication. Our functional assays showed that GINS4 was directly controlled by both strands of pre-miR-486, and its aberrant expression facilitated the aggressive behavior of LUAD cells. GINS4 is attractive as a therapeutic target for this disease. MiRNA analysis, including passenger strands, will further improve our understanding of the molecular pathogenesis of LUAD.

DOI： 10.3390/cells12141885

PubMed

Language：English  

DOI： 10.3390/biom13060893

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Cholinergic receptor muscarinic 3 (CHRM3)-mediated focal adhesion kinase/YES-associated protein (YAP) signalling is essential for the growth of castration-resistant prostate cancer (CRPC) cells. Here, we evaluated the molecular mechanisms through which CHRM3 overexpression facilitates castration-resistant growth. Small RNA sequencing combined with in silico analyses revealed that CHRM3 was a putative target of miR-15b-5p. Notably, androgen deprivation suppressed miR-15b-5p expression and increased CHRM3 expression. Moreover, miR-15b-5p bound directly to CHRM3 and inhibited YAP activation induced by CHRM3 stimulation. Furthermore, miR-15b-5p abolished the growth of CRPC cells induced by CHRM3 stimulation. We conclude that the miR-15b-5p/CHRM3/YAP signalling axis promotes the castration-resistant growth of prostate cancer.

DOI： 10.1002/1873-3468.14598

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

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 SCCLC 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. DONSON knockdown induced cell cycle arrest in SCLC cells, and DONSON overexpression was 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

PubMed

Language：English  

DOI： 10.1016/bs.acc.2022.09.004

PubMed

Language：Japanese   Publisher：(一社)日本呼吸器学会  

症例は86歳,男性.進展型小細胞肺癌と診断し,カルボプラチン(carboplatin)+エトポシド(etoposide)+アテゾリズマブ(atezolizumab)による1次治療を開始した.4コースの化学療法終了後,両眼の急速な視力低下が出現した.精査の結果,抗リカバリン抗体陽性の網膜症と診断した.アテゾリズマブの中止とステロイド治療により,視力障害は軽快した.肺癌の治療開始後に自己免疫機序の網膜症が発症することは稀であり,免疫チェックポイント阻害剤が関連している可能性が考えられた.(著者抄録)

Language：English   Publishing type：Research paper (scientific journal)  

A 44-year-old woman presented with cough, facial edema, and progressive fatigue. Computed tomography (CT) showed an anterior mediastinal mass, and laboratory findings showed liver injury. She was diagnosed with thymoma and scheduled for thymectomy after radiation and chemotherapy. However, she was referred to our department due to exacerbation of liver injury. Autoimmune hepatitis (AIH) was suspected based on the findings of elevated anti-nuclear antibody and immunoglobulin G levels. Histological findings of a liver biopsy confirmed the diagnosis of AIH. After oral steroid therapy initiation, she had diplopia and ptosis. Five days after steroid treatment, bulbar symptoms, such as nasal voice and dysarthria, appeared. A physical examination and electrophysiological tests confirmed myasthenia gravis (MG), and to prevent MG crisis, immunoadsorption plasmapheresis and tacrolimus were started by the neurologist. MG symptoms and liver damage gradually improved, she was then treated with chemotherapy and radiation for thymoma and underwent thymectomy, now showing no relapse of AIH or MG. We report the first case of MG developing immediately after the introduction of prednisolone for AIH complicated with thymoma.

DOI： 10.1007/s12328-022-01641-5

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Asparagine-linked glycosylation (N-glycosylation) of proteins in the cancer secretome has been gaining increasing attention as a potential biomarker for cancer detection and diagnosis. Small extracellular vesicles (sEVs) constitute a large part of the cancer secretome, yet little is known about whether their N-glycosylation status reflects known cancer characteristics. Here, we investigated the N-glycosylation of sEVs released from small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC) cells. We found that the N-glycans of SCLC-sEVs were characterized by the presence of structural units also found in the brain N-glycome, while NSCLC-sEVs were dominated by typical lung-type N-glycans with NSCLC-associated core fucosylation. In addition, lectin-assisted N-glycoproteomics of SCLC-sEVs and NSCLC-sEVs revealed that integrin αV was commonly expressed in sEVs of both cancer cell types, while the epithelium-specific integrin α6β4 heterodimer was selectively expressed in NSCLC-sEVs. Importantly, N-glycomics of the immunopurified integrin α6 from NSCLC-sEVs identified NSCLC-type N-glycans on this integrin subunit. Thus, we conclude that protein N-glycosylation in lung cancer sEVs may potentially reflect the histology of lung cancers.

DOI： 10.1016/j.jbc.2022.101950

PubMed

Language：Japanese   Publisher：(NPO)日本肺癌学会  

Language：Japanese   Publisher：(一社)日本呼吸器学会  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND AIMS: Immune checkpoint inhibitors (ICIs) are used to treat several cancers, but they sometimes induce immune-related adverse events (irAEs). Patients with irAEs often have improved antitumor responses, but discontinuation of ICIs after irAEs is considered necessary. Resuming the use of ICIs after irAEs is preferable, but few studies have investigated the safety of ICI resumption after irAEs. Therefore, we evaluated the factors associated with the recurrence of irAEs after ICI resumption to investigate the safety of this approach. METHODS: In this observational study, we enrolled patients treated with ICIs from September 2014 to March 2020 at our institution. Patient characteristics, ICIs, grades of irAEs, ICI discontinuation or resumption rates, and recurrence rates of irAEs after ICI therapy were analysed. RESULTS: Two-hundred eighty-seven patients were included in the present study, and 76 patients experienced grade 2 or higher irAEs. Forty-two patients underwent ICI resumption after recovering from irAEs, and 13 of them had a recurrence of irAEs. Among those 13 patients, six had a recurrence of the same irAE, and seven experienced other irAEs. Ten of the 13 patients had grade ≥2 irAEs, and none had fatal irAEs. In the grade 2 or higher irAE group, more patients had irAEs associated with multiple organs and of initial grade ≥2 than those in the grade 1 and no recurrent irAEs group. CONCLUSIONS: Patients with initial multisystemic irAEs and irAEs of grade ≥2 were more likely to experience relapse or develop new grade ≥2 irAEs after ICI resumption.

DOI： 10.1371/journal.pone.0267572

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

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

PubMed

Language：Japanese   Publisher：The Japan Society for Respiratory Endoscopy  

<p><b><i>Background.</i></b> Simultaneous occurrence of active tuberculosis and malignant tumor metastasis in the same lymph node lesion is rare. Due to the increased usage of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and improved technology, a high accuracy rate for diagnosis of lymph node lesions in the thoracic cavity has been observed. <b><i>Case.</i></b> A 78-year-old man had been treated for tongue squamous cell carcinoma and primary malignant lymphoma of the pancreas. He was admitted to our department because he presented with hoarseness and contrast-enhanced computed tomography showed left mediastinal and hilar lymphadenopathy with low central attenuation. In addition, EBUS-TBNA of the enlarged left lower paratracheal lymph node (#4L) was performed. Histopathological analysis revealed lymph node metastasis of tongue squamous cell carcinoma, and bacteriological analysis detected <i>Mycobacterium tuberculosis</i>. <b><i>Conclusion.</i></b> Here, we encountered a rare case of lymph node tuberculosis in the same lesion with mediastinal lymph node metastasis and disease recurrence of tongue squamous cell carcinoma. The coexistence of both diseases with similar imaging findings within an intrathoracic lymph node has not been reported. It could be diagnosed by minimally invasive EBUS-TBNA.</p>

DOI： 10.18907/jjsre.43.6_614

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

背景.同一リンパ節病巣内に活動性結核と悪性腫瘍の転移を同時に認めることは稀である.超音波気管支鏡ガイド下針生検(endobronchial ultrasound-guided transbronchial needle aspiration:EBUS-TBNA)の普及および技術向上により胸腔内のリンパ節病変に対する高い正診率が得られている.症例.78歳男性.舌扁平上皮癌と膵原発悪性リンパ腫の治療歴がある.嗄声を契機に造影CTで内部に低吸収域を伴う左縦隔および肺門リンパ節腫大を指摘され,当科に入院となった.腫大した左下部気管傍リンパ節(#4L)に対してEBUS-TBNAを施行した結果,病理組織検査で舌扁平上皮癌のリンパ節転移と診断し,さらに細菌学的検査で結核菌を検出した.結論.舌扁平上皮癌の縦隔リンパ節転移再発の同一病巣内にリンパ節結核を合併した症例を経験した.画像所見が類似する両疾患が胸腔内リンパ節に合併した報告はこれまでになく,低侵襲であるEBUS-TBNAにより診断し得た.(著者抄録)

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

背景.同一リンパ節病巣内に活動性結核と悪性腫瘍の転移を同時に認めることは稀である.超音波気管支鏡ガイド下針生検(endobronchial ultrasound-guided transbronchial needle aspiration:EBUS-TBNA)の普及および技術向上により胸腔内のリンパ節病変に対する高い正診率が得られている.症例.78歳男性.舌扁平上皮癌と膵原発悪性リンパ腫の治療歴がある.嗄声を契機に造影CTで内部に低吸収域を伴う左縦隔および肺門リンパ節腫大を指摘され,当科に入院となった.腫大した左下部気管傍リンパ節(#4L)に対してEBUS-TBNAを施行した結果,病理組織検査で舌扁平上皮癌のリンパ節転移と診断し,さらに細菌学的検査で結核菌を検出した.結論.舌扁平上皮癌の縦隔リンパ節転移再発の同一病巣内にリンパ節結核を合併した症例を経験した.画像所見が類似する両疾患が胸腔内リンパ節に合併した報告はこれまでになく,低侵襲であるEBUS-TBNAにより診断し得た.(著者抄録)

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00298&link_issn=&doc_id=20211216270008&doc_link_id=10.18907%2Fjjsre.43.6_614&url=https%3A%2F%2Fdoi.org%2F10.18907%2Fjjsre.43.6_614&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：English   Publishing type：Research paper (scientific journal)  

Afatinib is used to treat non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation as a second-generation EGFR-tyrosine kinase inhibitor (TKI). Early prediction of adverse effects based on the pharmacokinetics of afatinib enables support for quality of life (QOL) in patients with no change in efficacy. We examined the pharmacokinetic relationship between trough plasma concentration and adverse effects and evaluated the utility of measuring the trough plasma concentration of afatinib as the first EGFR-TKI treatment for NSCLC in a prospective multicenter study. Twenty-four patients treated with afatinib were enrolled in this study. All blood samples were collected at the trough point, and plasma concentrations were measured using high-performance liquid chromatography-tandem mass spectrometry. Logistic regression analysis for the dose reduction of afatinib was performed, and the receiver operating characteristic (ROC) curve was plotted. Although all patients started afatinib at 40 mg/day, plasma concentrations were variable, and mean and median trough plasma concentrations were 32.9 ng/mL and 32.5 ng/mL in this study, respectively. Minimum and maximum trough plasma concentrations were 10.4 ng/mL and 72.7 ng/mL, respectively. This variability was speculated to involve personal parameters such as laboratory data. However, no patient characteristics or laboratory data examined correlated with the trough plasma concentration of afatinib, except albumin. Albumin showed a weak correlation with plasma concentration (r = 0.60, p = 0.009). The trough plasma concentration of afatinib was significantly associated with the dose reduction of afatinib (p = 0.047). The area under the ROC curve (AUC) for the trough plasma concentration of afatinib was 0.81. The cut-off value was 21.4 ng/mL. The sensitivity and specificity of the cut-off as a risk factor were 0.80 and 0.75. In summary, the trough plasma concentration of afatinib was associated with continued or reduced dosage because of the onset of several adverse effects, and a threshold was seen. Adverse effects not only lower QOL but also hinder continued treatment. Measuring plasma concentrations of afatinib appears valuable to predict adverse effects and continue effective therapy.

DOI： 10.3390/cancers13143425

PubMed

Language：English  

DOI： 10.1111/pin.13109

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Tiotropium bromide, a long-acting muscarinic antagonist, reduces the frequency of exacerbation in patients with moderate to severe asthma, but its underlying mechanism is not clear. Asthma exacerbations are associated with exposure to external stimuli, and group 2 innate lymphoid cells (ILC2s) are considered to be involved in the pathophysiology of asthma exacerbation. We investigated whether tiotropium modulates airway inflammation through ILC2 functions. METHODS: Mice were administered papain intranasally to induce innate-type airway inflammation with or without tiotropium pretreatment, and bronchoalveolar lavage fluids (BALF) and lung tissues were collected. Lung-derived ILC2s and bone marrow-derived basophils were stimulated in vitro with IL-33 in the presence or absence of tiotropium. Muscarinic M3 receptor (M3R) expression on immune cells was assessed by RNA sequence. RESULTS: Papain induced airway eosinophilic inflammation, and tiotropium reduced the numbers of eosinophils in BALF. The concentrations of IL-4, IL-5, and IL-13, and the numbers of ILC2s in BALF were also reduced by tiotropium treatment. However, tiotropium did not affect IL-33-induced IL-5 and IL-13 production from ILC2s, suggesting that tiotropium regulates ILC2s indirectly. Gene-expression analysis showed that basophils predominantly expressed M3R mRNA among murine immune cells. Tiotropium reduced IL-4 production from basophils derived from mouse bone marrow and human basophils after stimulation with IL-33. CONCLUSIONS: These findings suggest that tiotropium attenuates ILC2-dependent airway inflammation by suppressing IL-4 production from basophils and, subsequently, regulating ILC2 activation. The inhibitory effects of long-acting muscarinic antagonists on the innate response may contribute to reducing asthma exacerbation.

DOI： 10.1111/all.14836

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

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

PubMed

Language：Japanese   Publisher：一般社団法人 日本臨床薬理学会  

<p>【目的】</p><p>　第二世代上皮成長因子受容体 (EGFR) チロシンキナーゼ阻害薬 (EGFR-TKI_s) であるアファチニブ (AFT) は、EGFR遺伝子変異陽性非小細胞肺癌患者に対する第一選択薬の一つである。初期投与路用は多くの患者が固定用量40 mgから開始されるが、血中濃度は個体差が大きいことが知られている。また、AFT投与中の患者の多くは、副作用の発現により減量あるいは休薬を経験する。そこで、本研究ではAFT血中濃度と副作用発現との関係や、患者背景や臨床検査値の中に血中濃度と相関性を示す項目を見つけ出すことで適切な投与量が設計可能かを検討した。</p><p>【方法】</p><p>　鹿児島大学病院臨床研究倫理委員会の承認と対象患者より文面での同意を取得し、AFTでの治療が開始となったEGFR-TKIs未治療のEGFR変異陽性非小細胞患者を対象に、液体クロマトグラフィー質量分析法 (LC-MS/MS) を用いてday8-14におけるAFTトラフ血中濃度測定を行った。AFTトラフ血中濃度と臨床検査値、有害事象、AFTの減量、無増悪生存期間について相関分析、ロジスティック解析、ログ・ランク検定を用いて統計解析を行った。</p><p>【結果・考察】</p><p>　臨床検査値の中にAFT血中濃度と強い相関性を示す項目はなかった。一方、AFT血中濃度が高い患者では減量となった症例がより多く、ロジスティック解析によりAFT血中濃度が高いことと投与量減量には有意な関連があることが示され、その血中濃度カットオフ値は21.4 ng/mLであった。また、減量あり群と減量なし群の無増悪生存期間はぞれぞれ415日と446日で違いはみられなかった。</p><p>【結論】</p><p>　AFT治療患者において、血中濃度のモニタリングを行うことは、副作用発現の予測ができ、患者のQOLの確保につながると考えられる。</p>

DOI： 10.50993/jsptsuppl.42.0_1-s17-1

Publisher：(NPO)日本呼吸器内視鏡学会  

背景.肺過誤腫は肺良性腫瘍の中で最も多いが、そのほとんどが肺実質型であり、気管支内腔型は比較的稀である。症例.40歳男性。閉塞性肺炎を契機に当科に入院となり、胸部CTで左下葉支内に腫瘍を指摘された。気管支鏡検査で左下葉支より突出する表面平滑なポリープ状腫瘍を認めた。生検で確定診断に至らず、後日、高周波スネアによる内視鏡的切除を行い軟骨性過誤腫と病理診断した。左B6c内腔に腫瘍が残存したため、根治術目的で胸腔鏡補助下左肺下葉S6区域切除術を施行したところ、術後病理で気管支内腫瘍の一部が肺実質にも進展していた。結論.気管支内腫瘍に対し気管支鏡下切除術を施行したところ、肺実質への進展も確認された肺過誤腫の症例を経験した。気管支内腔型肺過誤腫の診断に際しては、肺実質への進展を伴う症例もあり、その治療には注意が必要である。(著者抄録)

DOI： 10.3390/cells9092083

PubMed

DOI： 10.1136/esmoopen-2019-000656

PubMed

DOI： 10.1111/cas.14327

PubMed

DOI： 10.1016/j.lungcan.2019.11.014

PubMed

Publisher：The Japan Society for Respiratory Endoscopy  

<p><b><i>Background.</i></b> Pulmonary hamartoma is the most common benign lung tumor type. Most such cases are parenchymal hamartoma, while some are endobronchial hamartoma. <b><i>Case.</i></b> A 40-year-old man presenting with obstructive pneumonia was admitted to our hospital. An endobronchial tumor in the left lower lobar bronchus was observed on chest computed tomography. A bronchoscopic examination revealed a smooth-surfaced polypoid tumor occluding the left lower lobar bronchus. A transbronchial biopsy revealed no diagnostic findings, so bronchoscopic resection using electrosurgical snaring was performed. Accordingly, a histopathological analysis led to the diagnosis of endobronchial cartilaginous hamartoma. Since a tumor obstructing the orifice of the left B⁶c had persisted, video-assisted left S⁶ segmentectomy was performed for radical surgery. The postoperative pathological findings revealed that some parts of the endobronchial tumor had expanded to the pulmonary parenchyma. <b><i>Conclusion.</i></b> We herein report a case of pulmonary hamartoma that was confirmed to have expanded to the pulmonary parenchyma after bronchoscopic resection for an endobronchial tumor. In some cases of endobronchial hamartoma, expansion to the pulmonary parenchyma occurs, and caution must be exercised in its treatment.</p>

DOI： 10.18907/jjsre.42.6_524

DOI： 10.1002/rcr2.454

PubMed

DOI： 10.3390/ijms20184482

PubMed

Publisher：(一社)日本呼吸器学会  

症例は69歳、男性。左肺扁平上皮癌stage IIIBと胸部中部食道扁平上皮癌の同時性重複癌と診断し、化学療法を継続したが、病状は徐々に進行。6次治療ではあったが、performance status(PS)が良好であったので、ニボルマブ(nivolumab)投与を開始したところ、pseudoprogressionを経て肺癌と食道癌はいずれも縮小した。免疫チェックポイント阻害剤が奏効した同時性重複癌の報告は稀であり報告する。(著者抄録)

DOI： 10.3390/cancers11050601

PubMed

DOI： 10.3390/cancers11020258

PubMed

DOI： 10.1111/cas.13853

PubMed

DOI： 10.1038/s10038-018-0497-9

PubMed

DOI： 10.3892/ijo.2017.4232

PubMed

DOI： 10.1186/s12890-017-0534-z

PubMed

DOI： 10.3892/mco.2017.1394

PubMed

DOI： 10.1038/jhg.2016.47

PubMed

DOI： 10.2147/COPD.S130453

PubMed

Language：Japanese   Publisher：(一社)日本呼吸器学会  

Language：Japanese   Publisher：(一社)日本臨床薬理学会  

Language：English   Publisher：(一社)日本癌学会  

Language：English   Publisher：(一社)日本癌学会  

Language：Japanese   Publisher：(一社)日本呼吸器学会  

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