研究者詳細 - 宮島　正博

論文 - 宮島　正博

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The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells.

Daichi Ishii, Yuma Shindo, Wataru Arai, Takumi Konno, Takayuki Kohno, Kazuya Honda, Masahiro Miyajima, Atsushi Watanabe, Takashi Kojima

International journal of molecular sciences 25 ( 3 ) 2024年01月 [国際誌]

Tight junction (TJ) protein cingulin (CGN) and transcription factor forkhead box protein O1 (FOXO1) contribute to the development of various cancers. Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for some cancers. HDAC inhibitors affect the expression of both CGN and FOXO1. However, the roles and regulatory mechanisms of CGN and FOXO1 are unknown in non-small cell lung cancer (NSCLC) and normal human lung epithelial (HLE) cells. In the present study, to investigate the effects of CGN and FOXO1 on the malignancy of NSCLC, we used A549 cells as human lung adenocarcinoma and primary human lung epithelial (HLE) cells as normal lung tissues and performed the knockdown of CGN and FOXO1 by siRNAs. Furthermore, to investigate the detailed mechanisms in the antitumor effects of HDAC inhibitors for NSCLC via CGN and FOXO1, A549 cells and HLE cells were treated with the HDAC inhibitors trichostatin A (TSA) and Quisinostat (JNJ-2648158). In A549 cells, the knockdown of CGN increased bicellular TJ protein claudin-2 (CLDN-2) via mitogen-activated protein kinase/adenosine monophosphate-activated protein kinase (MAPK/AMPK) pathways and induced cell migration, while the knockdown of FOXO1 increased claudin-4 (CLDN-4), decreased CGN, and induced cell proliferation. The knockdown of CGN and FOXO1 induced cell metabolism in A549 cells. TSA and Quisinostat increased CGN and tricellular TJ protein angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) in A549. In normal HLE cells, the knockdown of CGN and FOXO1 increased CLDN-4, while HDAC inhibitors increased CGN and CLDN-4. In conclusion, the knockdown of CGN via FOXO1 contributes to the malignancy of NSCLC. Both HDAC inhibitors, TSA and Quisinostat, may have potential for use in therapy for lung adenocarcinoma via changes in the expression of CGN and FOXO1.

DOI PubMed

Experimental and histological evaluation of each clamp technique for pulmonary artery.

Yoshiki Chiba, Yuki Takahashi, Yoshiaki Takase, Kodai Tsuruta, Ryunosuke Maki, Masahiro Miyajima, Hirofumi Ohnishi, Atsushi Watanabe

Interdisciplinary cardiovascular and thoracic surgery 2023年07月 [査読有り] [国際誌]

OBJECTIVES: The double-loop technique has been used in our clinical settings for pulmonary arterioplasty and/or injured artery repair during thoracoscopic anatomical lung resection. We evaluated the pressure resistance capacity and intimal load to determine the effectiveness and safety of the double-loop technique. METHODS: The double-loop technique, DeBakey clamp, Fogarty clamp, endovascular clips, and vessel loop technique were evaluated. During an experimental study, a polyvinyl alcohol main pulmonary artery model, manometer, and in-deflation device were used to measure the burst pressure. The maximum clamp pressure was measured using a pressure-measuring film. Each measurement was performed 10 times. During the histological study, we measured the burst pressure and evaluated the intimal damage of the human pulmonary artery associated with the double-loop technique and DeBakey clamp. RESULTS: The experimental burst pressure (mmHg) and maximum clamp pressure (MPa) between the double-loop technique and DeBakey at the third notch were not significantly different (24.6 ± 2.8 and 21.8 ± 2.8, P = 0.094; 1.54 ± 0.12 and 1.49 ± 0.12, P = 0.954). During the histological study, the burst pressures of the double-loop technique and DeBakey at the third notch were also not significantly different (P = 0.754). Furthermore, the double-loop technique resulted in only intimal deformation in each five samples. CONCLUSIONS: The double-loop technique is feasible for thoracoscopic anatomical lung resection because it has similar pressure resistance capacity and intimal load as DeBakey at the third notch.

DOI PubMed

特集縦隔･胸壁腫瘍に対する低侵襲手術 1. ロボット支援下手術手術支援ロボットを用いた縦隔腫瘍に対する低侵襲手術-ポート配置の工夫と適応の変遷

槙龍之輔, 鶴田航大, 千葉慶宜, 石井大智, 大湯岳, 佐藤大軌, 宮島正博, 渡辺敦

胸部外科 ( 南江堂 ) 76 ( 7 ) 506 - 509 2023年07月 [査読有り]

DOI

Recognition of subsuperior segmental vein for thoracoscopic subsuperior segmentectomy.

Daichi Ishii, Yoshiaki Takase, Ryunosuke Maki, Yoshiki Chiba, Yuki Takahashi, Kodai Tsuruta, Masahiro Miyajima, Atsushi Watanabe

JTCVS techniques 19 135 - 139 2023年06月 [査読有り] [国際誌]

DOI PubMed

Metastatic pulmonary pleomorphic carcinoma replaced by a granulomatous lesion after spontaneous regression and PD-1 blockade-induced regression: can epithelioid granuloma be a histological hallmark of cancer immunity?

Naoki Shijubou, Yuichiro Asai, Michiko Hosaka, Keiko Segawa, Terufumi Kubo, Masahiro Miyajima, Tomohide Tsukahara, Yoshihiko Hirohashi, Takayuki Kanaseki, Kenji Murata, Atsushi Watanabe, Tadashi Hasegawa, Hirofumi Chiba, Toshihiko Torigoe

Immunological medicine 46 ( 2 ) 93 - 96 2023年06月 [国際誌]

Immune checkpoint inhibitors (ICIs) for various types of malignancy, including non-small-cell lung cancer, have improved prognosis in some cases. Granuloma formation after ICI administration suggests a tumor antigen-specific cytotoxic T cell response with abundant interferon-gamma production, which can be used to estimate the curative effect of ICIs. In this report, we present a case with a resected lung lesion, clinically suspected to be lung cancer, that consisted of a granulomatous lesion. A tumor was also found in the duodenum that was presumed to be derived from the pulmonary pleomorphic carcinoma. Duodenal tumor cells highly expressed PD-L1, suggesting PD-1/PD-L1 axis-mediated immune escape. As expected, pembrolizumab induced a complete response for the duodenal lesion. Interestingly, in histopathological analysis, the duodenal lesion was also replaced by an epithelial granuloma and multinucleated giant cells. We conclude that autoimmunity regressed the untreated primary lung lesion spontaneously, while the metastatic duodenal lesion responded to PD-1 blockade. Tumor-associated epithelioid granulomas, even before ICI administration, may be an important pathological finding indicating an immune response with interferon-gamma production by cytotoxic T cells to the tumor.

DOI PubMed

クリーゼ中に胸腺摘除術を施行し良好な転帰が得られた胸腺腫合併抗AChR抗体陽性全身型重症筋無力症の一例

河田由香, 種本真将, 山田稔, 横川和樹, 齋藤太郎, 岩原直敏, 松村晃寛, 鈴木秀一郎, 久原真, 高瀬貴章, 宮島正博, 渡辺敦

臨床神経学 ( (一社)日本神経学会 ) 63 ( 5 ) 325 - 325 2023年05月

Number of lymph nodes dissected and upstaging rate of the N factor in robot-assisted thoracic surgery versus video-assisted thoracic surgery for patients with cN0 primary lung cancer.

Yuma Shindo, Masahiro Miyajima, Yasuyuki Nakamura, Yoshiki Chiba, Wataru Arai, Miho Aoyagi, Ryunosuke Maki, Kodai Tsuruta, Yuki Takahashi, Makoto Tada, Yoshiaki Takase, Atsushi Watanabe

Surgery today 53 ( 4 ) 428 - 434 2023年04月 [査読有り] [国内誌]

PURPOSE: The accuracy of lymph node (LN) dissection in robotic surgery for lung cancer remains controversial. We compared the accuracy of LN dissection in robot-assisted thoracic surgery (RATS) vs. video-assisted thoracic surgery (VATS). METHODS: The subjects of this retrospective analysis were 226 patients with cN0 primary lung cancer who underwent robot-assisted or video-assisted thoracic lobectomy with LN dissection, in our department, between April, 2016 and February, 2021. We compared the numbers of all LNs and mediastinal LNs dissected, the time required for LN dissection, complications, and upstaging rates of the N factor between the groups. Furthermore, we performed an inverse probability of treatment weighting-adjusted analysis to reduce potential bias between the groups. RESULTS: The number of dissected LNs was higher in the RATS group in both the unweighted and weighted analyses. The time required for lymph node dissection was also longer in RATS. There was no significant difference in complications or in the upstaging rate of the N factor between the groups. CONCLUSION: More LNs were dissected with RATS. Thus, the usefulness of robot-assisted surgery for LN dissection needs to be investigated further.

DOI PubMed

Downregulation of angulin-1/LSR induces malignancy via upregulation of EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma A549 cells.

Wataru Arai, Takumi Konno, Takayuki Kohno, Yuki Kodera, Mitsuhiro Tsujiwaki, Yuma Shindo, Hirofumi Chiba, Masahiro Miyajima, Yuji Sakuma, Atsushi Watanabe, Takashi Kojima

Oncotarget 14 261 - 275 2023年03月 [査読有り] [国際誌]

Abnormal expression of bicellular tight junction claudins, including claudin-2 are observed during carcinogenesis in human lung adenocarcinoma. However, little is known about the role of tricellular tight junction molecule angulin-1/lipolysis-stimulated lipoprotein receptor (LSR). In the lung adenocarcinoma tissues examined in the present study, expression of claudin-2 was higher than in normal lung tissues, while angulin-1/LSR was poorly or faintly expressed. We investigated how loss of angulin-1/LSR affects the malignancy of lung adenocarcinoma cell line A549 and normal human lung epithelial (HLE) cells. The EGF receptor tyrosine kinase inhibitor AG1478 prevented the increase of claudin-2 expression induced by EGF in A549 cells. Knockdown of LSR induced expression of claudin-2 at the protein and mRNA levels and AG1478 prevented the upregulation of claudin-2 in A549 cells. Knockdown of LSR induced cell proliferation, cell migration and cell metabolism in A549 cells. Knockdown of claudin-2 inhibited the cell proliferation but did not affect the cell migration or cell metabolism of A549 cells. The TGF-β type I receptor inhibitor EW-7197 prevented the decrease of LSR and claudin-2 induced by TGF-β1 in A549 cells and 2D culture of normal HLE cells. EW-7197 prevented the increase of cell migration and cell metabolism induced by TGF-β1 in A549 cells. EW-7197 prevented the increase of epithelial permeability of FITC-4kD dextran induced by TGF-β1 in 2.5D culture of normal HLE cells. In conclusion, downregulation of angulin-1/LSR induces malignancy via EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma.

DOI PubMed

症例ロボット支援下手術で摘出した後縦隔Müller管囊胞の1例

仲澤順二, 石井大智, 大湯岳, 佐藤太軌, 千葉慶宜, 高橋有毅, 槙龍之輔, 鶴田航大, 高瀬貴章, 宮島正博, 中島慎治, 渡辺敦

胸部外科 ( 南江堂 ) 76 ( 3 ) 246 - 250 2023年03月 [査読有り]

DOI

[Mullerian Cyst in the Posterior Mediastinum Resected by Robot-assisted Thoracic Surgery:Report of a Case].

Junji Nakazawa, Daichi Ishii, Takeshi Oyu, Taiki Sato, Yoshiki Chiba, Yuki Takahashi, Ryunosuke Maki, Kodai Tsuruta, Yoshiaki Takase, Masahiro Miyajima, Shinji Nakajima, Atsushi Watanabe

Kyobu geka. The Japanese journal of thoracic surgery 76 ( 3 ) 246 - 250 2023年03月 [査読有り] [国内誌]

Mullerian cyst in the posterior mediastinum is a rare disorder. We report on the case of a woman in her 40s with a cystic nodule which is located in the right posterior mediastinum next to the vertebra at the level of tracheal bifurcation. The tumor was suggested to be cystic by preoperative magnetic resonance imaging (MRI). The tumor was resected with robot-assisted thoracic surgery. Pathology by hematoxylin-and-eosin (H&E) revealed a thin-walled cyst lined by ciliated epithelium without cellular atypia. The diagnosis of Mullerian cyst was confirmed by immunohistochemical staining which showed the positive findings for estrogen receptor (ER) and progesterone receptor of the lining cells.

PubMed

特集肺癌縮小手術における工夫と現況 1. 区域切除の実際と手技低侵襲肺悪性腫瘍縮小手術に対する手術手技の工夫

鶴田航大, 宮島正博, 石井大智, 大湯岳, 佐藤太軌, 千葉慶宜, 高橋有毅, 槙龍之輔, 高瀬貴章, 渡辺敦

胸部外科 ( 南江堂 ) 76 ( 1 ) 9 - 13 2023年01月 [査読有り]

DOI

[Novel Surgical Techniques for Lung Segmentectomy of Malignant Lung Tumors].

Kodai Tsuruta, Masahiro Miyajima, Daichi Ishii, Takeshi Oyu, Taiki Sato, Yoshiki Chiba, Yuki Takahashi, Ryunosuke Maki, Yoshiaki Takase, Atsushi Watanabe

Kyobu geka. The Japanese journal of thoracic surgery 76 ( 1 ) 9 - 13 2023年01月 [査読有り] [国内誌]

For a long time, lobectomy and lymph node dissection have been the standard surgery for treating non-small cell lung cancer. Recently, segmentectomy has been introduced as an alternative surgical procedure for treating early-stage lung cancer. Moreover, a growing number of segmentectomies are performed due to the increasing number of elderly patients, and the expansion of indications, including early- stage lung cancer with a ground glass nodule or peripheral nodule under 2 cm in diameter. However, the use of segmentectomy remains under debate. We have been performing thoracoscopic lung segmentectomy for malignant lung tumors since 2003. The number of surgeries has increased over the past few years, since robot-assisted lung resection of the right lobe became covered by health insurance in April 2018. In addition, lung segmentectomy is performed for lung metastases of malignant tumors in other organs. In deciding on the surgical approach, the increased technical difficulty of segmentectomy compared to lobectomy, owing to the anatomical complexity of the peripheral vessels and bronchi, needs to be considered, and novel surgical procedures and preoperative planning based on three-dimensional computed tomography( CT) images are necessary. We describe the preoperative management and surgical techniques used in approximately 250 lung segmentectomy procedures performed at our hospital up to May 2022, with no conversion to thoracotomy.

PubMed

留置マーカーの術中変位により肺切除範囲を拡大した転移性肺腫瘍の1例

石井大智, 髙瀬貴章, 千葉慶宜, 鶴田航大, 宮島正博, 渡辺敦

日本臨床外科学会雑誌 ( 日本臨床外科学会 ) 84 ( 1 ) 76 - 81 2023年 [査読有り]

触診が困難な小結節に対する肺部分切除術では，マーキングが有用である．近年，気管支鏡を用いたデジタルマーキング技術である，radiofrequency identification （RFID）が臨床応用された．RFIDマーキングは肺深部に存在する病変でも位置同定を可能とする．しかし，その合併症に関する報告はほとんどない．今回，気管支に留置されたRFIDタグが術中に変位する症例を経験したので報告する．患者は71歳，女性．転移性肺腫瘍疑い（左肺S10に8mm大の結節影）に対し，2箇所にRFIDタグを留置し，部分切除術を施行したところ，術中にタグの1つが気管支中枢側へ変位した．このタグを病変と一塊にして切除するため，結果的に切除肺の拡大を要した．原因として，鉗子の把持操作や自動縫合器による複数回のクランプが考えられた．部分切除では単一病変に対しタグ1つを末梢気管支に留置することを原則とし，留置部近傍での鉗子操作は避けるべきである．

DOI

今月の話題肺癌に対する右肺S6＋S＊区域切除

石井大智, 槙龍之輔, 大湯岳, 佐藤太軌, 千葉慶宜, 髙橋有毅, 鶴田航大, 髙瀬貴章, 宮島正博, 渡辺敦

胸部外科 ( 南江堂 ) 75 ( 13 ) 1088 - 1091 2022年12月 [査読有り]

DOI

[Thoracoscopic Superior and Subsuperior Segmentectomy of the Right Lower Lung for Lung Cancer].

Daichi Ishii, Ryunosuke Maki, Takeshi Ohyu, Taiki Sato, Yoshiki Chiba, Yuki Takahashi, Kodai Tsuruta, Yoshiaki Takase, Masahiro Miyajima, Atsushi Watanabe

Kyobu geka. The Japanese journal of thoracic surgery 75 ( 13 ) 1088 - 1091 2022年12月 [査読有り] [国内誌]

The subsuperior segment (S*) is not frequently observed between the superior (S6) and posterior basal segments (S10). We present a case of video-assisted thoracoscopic surgery of S6+S* segmentectomy for a primary lung cancer patient. A 71-year-old man with a 20-mm nodule on the right S6, suspected of primary lung cancer( cT1bN0M0, stageⅠA2), was admitted to our hospital. Three-dimensional chest computed tomography (CT) revealed a subsuperior segmental bronchus (B*), originating from the common trunk of the lateral basal segmental bronchus( B9) and posterior basal segmental bronchus (B10). In order to obtain enough surgical margin, we performed S6+S* segmentectomy. The pathological diagnosis was invasive adenocarcinoma( pT1cN0M0, stageⅠA3). S* segmentectomy was considered to be useful method to ensure sufficient surgical margin when the lesion is in S* or in segments adjacent to it.

PubMed

Robotic free pericardial fat pledget technique for treating pulmonary air leak.

Yoshiaki Takase, Yuki Takahashi, Masahiro Miyajima, Atsushi Watanabe

JTCVS techniques 16 153 - 156 2022年12月 [査読有り] [国際誌]

DOI PubMed

肺腺癌におけるタイト結合分子cingulinおよび転写因子FOXO1の役割

石井大智, 進藤悠真, 新井航, 金野匠, 幸野貴之, 宮島正博, 小島隆, 渡辺敦

肺癌 ( (NPO)日本肺癌学会 ) 62 ( 6 ) 635 - 635 2022年11月

Clinical effect of soft coagulation for air leak treatment during pulmonary lobectomy.

Yuki Takahashi, Ryunosuke Maki, Kodai Tsuruta, Makoto Tada, Wataru Arai, Yuma Shindo, Yasuyuki Nakamura, Masahiro Miyajima, Atsushi Watanabe

Journal of cardiothoracic surgery 17 ( 1 ) 253 - 253 2022年10月 [査読有り] [国際誌]

BACKGROUND: Soft coagulation using the VIO soft coagulation system is used to treat minor lung air leaks during pulmonary resection in Japan. We previously reported that it has a similar effect as the air leak treatment with fibrin glue. We evaluated the efficacy of soft coagulation using the VIO soft coagulation system for lung air leakage during pulmonary resection. METHODS: Intraoperative air leaks from the interlobar lung parenchyma were observed in 42 of the 283 patients who underwent video-assisted thoracoscopic surgery lobectomy between 2016 and 2018. We retrospectively reviewed these 42 patients who were treated using the VIO soft coagulation system for air leaks. We classified the air leaks in to grades using the Macchiarini scale score and evaluated the surgical outcomes of air leak treatment. RESULTS: Air leaks from the interlobar lung parenchyma having Macchiarini scale scores 1, 2, and 3 occurred in 8, 17, and 17 patients, respectively. In all the 8 patients with score 1 air leaks (100%), the air leaks could be controlled using the VIO soft coagulation system alone, and none had delayed pneumothorax requiring intervention. Of the score 2 and 3 air leaks, 52.9% and 35.3% were controlled using the VIO soft coagulation system alone, respectively. CONCLUSIONS: Macchiarini scale score 1 air leaks from the interlobar lung parenchyma could be well controlled using the VIO soft coagulation system. Therefore, soft coagulation with this system may be an alternative method for treating minor air leaks during pulmonary resection surgery.

DOI PubMed

Causes and management of intraoperative complications in robot-assisted anatomical pulmonary resection for lung cancer.

Yoshiaki Takase, Masahiro Miyajima, Yoshiki Chiba, Daichi Ishii, Taiki Sato, Yuma Shindo, Yasuyuki Nakamura, Miho Aoyagi, Kodai Tsuruta, Atsushi Watanabe

Journal of thoracic disease 14 ( 9 ) 3221 - 3233 2022年09月 [査読有り] [国際誌]

BACKGROUND: To perform safe robot-assisted anatomical lung resections, the details of intraoperative complications need to be shared among thoracic surgeons. However, only limited data are available. METHODS: This retrospective, single-institutional study evaluated 134 patients who underwent robot-assisted anatomical lung resection. We examined the causes, management, and outcomes of all intraoperative complications. RESULTS: Of the 134 eligible patients, 118 (88%) underwent lobectomy and 16 (12%) underwent segmentectomy. Intraoperative complications occurred in 17 (12.7%) patients. These complications included pulmonary artery (PA) injuries in seven patients, pulmonary vein (PV) injuries in three, azygos vein (AV) injury in one, superior vena cava (SVC) injury in one, bronchial injuries in three, and lung injuries in four. Most PA injuries were at a distal side and controlled by pressure, fibrin sealant, or stapling of the proximal side. In the three PV injuries, right upper PV was sandwiched by robotic instruments, V6 was punctured by the tip of the Maryland bipolar forceps, and the distal side of V2t was injured during tunneling of a minor interlobar fissure. These were controlled the same way as the PA injuries. The AV injury occurred during hilar lymph node (LN) dissection and was controlled by suturing. The SVC injury was caused by interference of the robotic forceps and the suction tube outside the field of view during upper mediastinal LN dissection. The injury was controlled by continuous pressure while layering polyglycolic acid sheets and fibrin glue. In the three bronchial injuries, B10 was injured during subcarinal LN dissection, right main bronchus was injured during upper bronchus dissection and the stapling failure of the bronchus occurred by strong traction. They were all repaired by suturing. All lung parenchymal injuries were caused by manipulation of robotic instruments outside the field of view. The lung injuries were repaired by suturing with pledgets. No cases were converted to thoracotomy. The 30-day mortality rate was 0.7%. The cause of mortality was pneumonia. CONCLUSIONS: In robot-assisted anatomical pulmonary resection for lung cancer, most major intraoperative complications can be safely managed robotically without conversion to thoracotomy.

DOI PubMed

臨床経験エキノコックス症による縦隔･肝臓病変に対する一期的手術

宇塚武司, 武川慶, 内山博貴, 在原綾香, 橋口仁喜, 山田健司, 宮島正博, 横田良一, 佐々木昭彦

胸部外科 ( 南江堂 ) 75 ( 9 ) 674 - 677 2022年09月 [査読有り] [国内誌]

Cystic echinococcosis is an uncommon zoonosis in Japan. Typical location of the cyst is the liver and the lung. Mediastinal hydatidosis is found in less than 0.1% of all hydatid disease patients. We report a rare case of 68 years old male with mediastinal and liver hydatid cysts. Serological test confirmed the diagnosis of hydatidosis. The patient underwent complete resection of mediastinal and liver cysts successfully. Postoperative follow-up for two years has not shown any signs of recurrence. Simultaneous resection of the cysts in different sites including mediastinum is rare and has not been reported in Japan. Hydatid disease is an important differential diagnosis for patient who has cryptogenic liver cyst and history of contact to wildlife or unsterile water.

DOI PubMed

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