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   Publisher：エルゼビア・ジャパン(株)  

症例は72歳男性で、44年間にわたり喫煙歴(1日2箱)があり、嗄声のため当院を受診した。左上葉の切除不能局所進行腺癌と診断し、シスプラチン、ビノレルビン、胸部原体照射による同時化学放射線療法を施行した。治療終了時に客観的腫瘍縮小効果が見られたため、デュルバルマブによる強化療法を行った。しかし、同薬による肺臓炎を発症したため、治療を中止し、プレドニゾロンで治療を行った。その後のCTで縦隔リンパ節と肺への転移を認め、原発巣はEGFR L858R陽性であったことから、オシメルチニブの連日投与を行った。しかし、12ヵ月後のCTで疾患進行が見られ、肺転移の再生検でEGFR L858RおよびBRAF V600E変異陽性が明らかとなった。患者同意のもと分子標的療法を選択し、ダブラフェニブとトラメチニブの投与を行い2ヵ月後に病勢安定となった。

Language：Japanese   Publisher：Respiratory Investigation  

Osimertinib has demonstrated efficacy as the first- and second-line treatment for advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations. However, EGFR-mutant NSCLC cells often acquire resistance to osimertinib. V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation (BRAF V600E) was detected in a re-biopsy (LC-SCRUM-TRY testing) of a patient with advanced lung adenocarcinoma who was resistant to osimertinib treatment. Currently, the patient is receiving dabrafenib/trametinib combination therapy and is under observation; a slight shrinking effect of cancer has been observed.

DOI： 10.1016/j.resinv.2023.09.006

Scopus

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

Scopus

PubMed

Language：Japanese   Publisher：Cells  

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

Scopus

PubMed

Language：Japanese  

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Language：Japanese