Faculty Profiles - akihide Tanimoto

Papers - akihide Tanimoto

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田代葵子, 上笹貫太郎, 堀之内道子, 谷本昭英, 坂本泰二 . インターフェロン-β結膜下注射が奏効した結膜悪性黒色腫の1例 . 臨床眼科75 ( 13 ) 1650 - 1656 2021.12Reviewed

Language：Japanese Publisher：(株)医学書院

＜文献概要＞目的:インターフェロン-β(IFN-β)結膜下注射の頻回投与で縮小に至った結膜悪性黒色腫の症例を報告する。症例:患者は91歳,女性。20XX年8月に増大と出血を伴う右下眼瞼結膜の隆起性腫瘤を自覚し,加療を目的として鹿児島大学病院眼科を紹介された。高血圧症,糖尿病,ネフローゼ症候群の既往があった。所見:初診時,右下眼瞼結膜に15mm大の出血を伴う隆起性腫瘤を認めた。拡大切除術を提案したが,高齢のため外科的治療を希望しなかった。下眼瞼結膜腫瘤を部分切除し,悪性黒色腫と組織診断した。全身検査では遠隔転移は検出されなかった。出血傾向の改善のため放射線治療(線量28Gy/14Fr)を行ったのち,IFN-β結膜下注射(300万単位/回)の継続で経過観察した。1回目の注射後から出血傾向は改善した。さらに週1回で注射を継続したところ,投与開始後3回目より隆起性病変は縮小を認め,8回目でほぼ消失した。副作用として視力低下を認めたため,投与間隔を延ばし,1回量を半減して投与を継続した。その後も病変の増悪や遠隔転移は認めなかったが,投与開始から8ヵ月後に既往のネフローゼ症候群の悪化を認めたため治療を中止した。結論:IFN-β結膜下注射は結膜悪性黒色腫の治療に有効であった。しかし,眼局所および全身に副作用を及ぼす可能性があり,投与量および投与間隔に注意が必要である。

林知実, 門野潤, 井上真岐, 坂元昭彦, 二渡久智, 平木翼, 谷本昭英, 風呂井彰 . Dubin-Johnson症候群に発生した肝細胞癌の1例 . 日本臨床外科学会雑誌82 ( 12 ) 2262 - 2269 2021.12Reviewed

Language：Japanese Publisher：日本臨床外科学会

肝細胞癌(HCC)を合併したDubin-Johnson症候群(DJS)の肝予備能評価と周術期経過を報告する.66歳の男性がRickettsia属による感染の際に肝障害と肝S4,S2にHCCを指摘された.T-bil 4.6(D-bil 3.4)mg/dL,Alb 4.2g/dL,PT 92%,indocyanine green 15分停滞率(ICGR15)11%,Child-Pugh B(7点),肝障害度Aであった,99mTc-galactosyl human serum albumin(GSA)シンチグラフィのLHL15は0.909で,肝予備能はほぼ正常と判断し,肝内側区域切除術+S2部分切除術を行った.術後3日目にT-bilが15.7mg/dLまで上昇したが28日目に術前値に復した.ICGR15とGSAシンチグラフィは正確に肝予備能を反映した.術後のT-bilの上昇は一過性であった.(著者抄録)

Shinichi Togami, Takashi Ushiwaka, Ikumi Kitazono, Shintaro Yanazume, Masaki Kamio, Akihide Tanimoto, Hiroaki Kobayashi . One-step nucleic acid amplification (OSNA) assay for detecting lymph node metastasis in cervical and endometrial cancer: a preliminary study. . Journal of gynecologic oncology33 ( 2 ) e11 2021.11Reviewed International journal

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

OBJECTIVE: To evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay for the diagnosis of lymph node (LN) metastasis in uterine cancer. METHODS: A total of 116 LNs from 30 patients with cervical and endometrial cancer, enrolled in this prospective study, were used. Excised LNs were cut into 4 to 6 blocks at 2 mm intervals, and nonadjacent blocks were alternately subjected to either histological examination or the OSNA assay. RESULTS: The concordance rate between histological examination and the OSNA assay in cervical cancer and in endometrial cancer was 95.9% and 95.2%, respectively. The sensitivity, specificity, and negative predictive value of the OSNA assay were 80%, 97.7%, and 97.7% in cervical cancer, and 85.7%, 93.3%, and 98.2% in endometrial cancer, respectively. In cervical cancer, discordant results were observed in 2 out of 49 LNs (4.1%); 1 was OSNA assay-positive and histological examination-negative, and 1 was OSNA assay-negative and histological examination-positive. In endometrial cancer, discordant results were observed in 5 out of 67 LNs (7.5%); 4 were OSNA assay-positive and histological examination-negative, and 1 was OSNA assay-negative and histological examination-positive. CONCLUSION: The OSNA assay showed high concordance rate with histological examination, sensitivity, and specificity in uterine cancer, suggesting that it could enhance the accuracy of conventional pathological examination for the detection of LN metastasis by reducing false negative rate.

DOI： 10.3802/jgo.2022.33.e11

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Kaori Kato, Masato Tsutsui, Shingo Noguchi, Yukitoshi Iha, Keisuke Naito, Takaaki Ogoshi, Chinatsu Nishida, Masahiro Tahara, Hirotaka Yamashita, Ke-Yong Wang, Yumiko Toyohira, Nobuyuki Yanagihara, Hiroaki Masuzaki, Hiroaki Shimokawa, Akihide Tanimoto, Kazuhiro Yatera . Spontaneous pulmonary emphysema in mice lacking all three nitric oxide synthase isoforms. . Scientific reports11 ( 1 ) 22088 - 22088 2021.11Reviewed International journal

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

The roles of endogenous nitric oxide (NO) derived from the entire NO synthases (NOSs) system have yet to be fully elucidated. We addressed this issue in mice in which all three NOS isoforms were deleted. Under basal conditions, the triple n/i/eNOSs-/- mice displayed significantly longer mean alveolar linear intercept length, increased alveolar destructive index, reduced lung elastic fiber content, lower lung field computed tomographic value, and greater end-expiratory lung volume as compared with wild-type (WT) mice. None of single NOS-/- or double NOSs-/- genotypes showed such features. These findings were observed in the triple n/i/eNOSs-/- mice as early as 4 weeks after birth. Cyclopaedic and quantitative comparisons of mRNA expression levels between the lungs of WT and triple n/i/eNOSs-/- mice by cap analysis of gene expression (CAGE) revealed that mRNA expression levels of three Wnt ligands and ten Wnt/β-catenin signaling components were significantly reduced in the lungs of triple n/i/eNOSs-/- mice. These results provide the first direct evidence that complete disruption of all three NOS genes results in spontaneous pulmonary emphysema in juvenile mice in vivo possibly through down-regulation of the Wnt/β-catenin signaling pathway, demonstrating a novel preventive role of the endogenous NO/NOS system in the occurrence of pulmonary emphysema.

DOI： 10.1038/s41598-021-01453-6

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Toshiyuki Nagata, Kentaro Minami, Masatatsu Yamamoto, Tsubasa Hiraki, Masashi Idogawa, Katsumi Fujimoto, Shun Kageyama, Kazuhiro Tabata, Kohichi Kawahara, Kazuhiro Ueda, Ryuji Ikeda, Yukio Kato, Masaaki Komatsu, Akihide Tanimoto, Tatsuhiko Furukawa, Masami Sato . BHLHE41/DEC2 Expression Induces Autophagic Cell Death in Lung Cancer Cells and Is Associated with Favorable Prognosis for Patients with Lung Adenocarcinoma. . International journal of molecular sciences22 ( 21 ) 2021.10Reviewed International journal

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

Lung cancer constitutes a threat to human health. BHLHE41 plays important roles in circadian rhythm and cell differentiation as a negative regulatory transcription factor. This study investigates the role of BHLHE41 in lung cancer progression. We analyzed BHLHE41 function via in silico and immunohistochemical studies of 177 surgically resected non-small cell lung cancer (NSCLC) samples and 18 early lung squamous cell carcinoma (LUSC) cases. We also examined doxycycline (DOX)-inducible BHLHE41-expressing A549 and H2030 adenocarcinoma cells. BHLHE41 expression was higher in normal lung than in lung adenocarcinoma (LUAD) tissues and was associated with better prognosis for the overall survival (OS) of patients. In total, 15 of 132 LUAD tissues expressed BHLHE41 in normal lung epithelial cells. Staining was mainly observed in adenocarcinoma in situ and the lepidic growth part of invasive cancer tissue. BHLHE41 expression constituted a favorable prognostic factor for OS (p = 0.049) and cause-specific survival (p = 0.042) in patients with LUAD. During early LUSC, 7 of 18 cases expressed BHLHE41, and this expression was inversely correlated with the depth of invasion. DOX suppressed cell proliferation and increased the autophagy protein LC3, while chloroquine enhanced LC3 accumulation and suppressed cell death. In a xenograft model, DOX suppressed tumor growth. Our results indicate that BHLHE41 expression prevents early lung tumor malignant progression by inducing autophagic cell death in NSCLC.

DOI： 10.3390/ijms222111509

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Hirotsugu Noguchi, Michiyo Higashi, Ryo Desaki, Takashi Tasaki, Mari Kirishima, Ikumi Kitazono, Kazuhiro Tabata, Akihide Tanimoto . Adult Hepatocellular Carcinoma Coexisting with Extramedullary Hematopoiesis. . International journal of surgical pathology30 ( 3 ) 10668969211050904 - 10668969211050904 2021.10Reviewed International journal

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

Extramedullary hematopoiesis (EMH) in adults usually occurs in the liver, spleen, and lymph nodes when bone marrow hematopoiesis fails. EMH has also been recognized in benign or malignant hepatic tumors, such as hepatoblastoma, hepatocellular adenoma, and vascular tumors. However, it is rarely encountered in hepatocellular carcinoma (HCC) in elderly adults, and the molecular mechanism of EMH in hepatic tumors remains unclear. We present a case of a 74-year-old man without any hematopoietic disorders and hepatitis viral infection who underwent hepatic resection for HCC. Histological examination revealed a well-differentiated HCC with trilineage hematopoiesis in the tumor and non-neoplastic liver. The coexistence of HCC and EMH in adult patients with no hematopoietic disorders is very rare and must be distinguished from poorly differentiated or dedifferentiated HCC and hepatoblastoma.

DOI： 10.1177/10668969211050904

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Tokuro Baba, Takafumi Kawano, Yusuke Saito, Shun Onishi, Koji Yamada, Waka Yamada, Ryuta Masuya, Kazuhiko Nakame, Yota Kawasaki, Satoshi Iino, Masahiko Sakoda, Mari Kirishima, Tatsuru Kaji, Akihide Tanimoto, Shoji Natsugoe, Takao Ohtsuka, Hiroshi Moritake, Satoshi Ieiri . Malignant perivascular epithelioid cell neoplasm in the liver: report of a pediatric case. . Surgical case reports7 ( 1 ) 212 - 212 2021.9Reviewed International journal

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

BACKGROUND: Perivascular epithelioid cell neoplasm (PEComa) in a child is very rare. We herein report the first malignant case of PEComa developing in the liver of a pediatric patient. CASE PRESENTATION: A 10-year-old boy visited a private clinic with prolonged fever of unknown etiology. Abdominal ultrasonography was performed to evaluate the fever's origin, revealing a large tumor in the liver. He was thus referred to a nearby hospital to investigate the tumor further. Enhanced computed tomography (CT) showed a 6.8 × 5.9 × 10.5-cm solid lesion on S4 and S5. On magnetic resonance imaging (MRI), the tumor had a low signal intensity on T1 imaging and high signal intensity on T2 imaging, with partial diffusion restriction. 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) showed a marked uptake in the mass lesion with no evidence of metastasis. The patient was negative for all tumor markers, including AFP, CEA and PIVKA-II. The results of a needle biopsy suggested hepatocellular carcinoma. The tumor's rapid growth suggested malignancy. Hepatic segmentectomy (S4 + S5 + S8) was performed. The tumor was resected en bloc with a margin. Microscopically, the tumor showed atypical spindle, polygonal or oval-shaped cells with a high nuclear grade, and vascular invasion. Immunohistochemistry was positive for alpha-smooth muscle antigen (α-SMA), human melanin black-45 (HMB-45) and melan A. The pathological diagnosis was malignant PEComa. In the 6 months after surgery, the patient complained of shoulder pain. MRI showed a dumbbell-shaped tumor at the 2nd thoracic vertebrae, which was confirmed to be bone metastasis of PEComa. After chemotherapy, including ifosfamide and doxorubicin, vertebrectomy was performed. Two years later, thoracoabdominal CT showed a 10-cm solid mass occupying the pelvis and a 15-mm nodule in the middle lobe of the right lung. Under a diagnosis of peritoneal and lung metastases, they were surgically removed and metastasis of PEComa was pathologically confirmed. Four months after the 2nd relapse, pelvic metastasis appeared again and mTOR (mammalian target of rapamycin) inhibitor was initiated. To our knowledge, this is the first report of malignant hepatic PEComa in a pediatric patient. CONCLUSION: Although extremely rare, malignant hepatic PEComa can develop in a child.

DOI： 10.1186/s40792-021-01300-w

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Yuto Hozaka, Hiroshi Kurahara, Hideyuki Oi, Tetsuya Idichi, Yoichi Yamasaki, Yota Kawasaki, Kiyonori Tanoue, Megumi Jinguji, Masatoyo Nakajo, Atsushi Tani, Akihiro Nakajo, Yuko Mataki, Yoshihiko Fukukura, Hirotsugu Noguchi, Michiyo Higashi, Takashi Yoshiura, Akihide Tanimoto, Takao Ohtsuka . Clinical Utility and Limitation of Diagnostic Ability for Different Degrees of Dysplasia of Intraductal Papillary Mucinous Neoplasms of the Pancreas Using 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography. . Cancers13 ( 18 ) 2021.9Reviewed International journal

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

The diagnostic value of 18F-fluorodeoxyglucose (FDG) uptake in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas remains unclear. This study aimed to assess the role of FDG uptake in the diagnosis of different degrees of dysplasia of IPMNs. We retrospectively analyzed the following three points in 84 patients with IPMNs: (1) risk factors to predict high-grade dysplasia (HGD) and invasive carcinoma (INV); (2) the relationship between FDG uptake and glucose transporter 1 (GLUT-1) expression; and (3) the relationship between FDG uptake and the presence of mural nodules. The histopathological diagnosis was low-grade dysplasia (LGD) in 43 patients, HGD in 16, and INV in 25. The maximum standardized uptake value (SUV-max) was significantly higher in INV than in LGD/HGD (p < 0.0001, p = 0.0136). The sensitivity and specificity to discriminate INV from LGD/HGD were 80.0% and 86.2%, respectively, using the receiver operator characteristic curve, when the optimal cutoff score of SUV-max was set at 4.03. Those values were not different between HGD and LGD. More than half of HGD patients had low GLUT-1 expression. Taken together, FDG-PET/CT is useful in distinguishing between non-invasive and invasive IPMN. Our results offer critical information that may determine surgical treatment strategies.

DOI： 10.3390/cancers13184633

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Baba Tokuro, Kawano Takafumi, Saito Yusuke, Onishi Shun, Yamada Koji, Yamada Waka, Masuya Ryuta, Nakame Kazuhiko, Kawasaki Yota, Iino Satoshi, Sakoda Masahiko, Kirishima Mari, Kaji Tatsuru, Tanimoto Akihide, Natsugoe Shoji, Ohtsuka Takao, Moritake Hiroshi, Ieiri Satoshi . 肝悪性血管周囲類上皮細胞腫瘍　1小児例の報告(Malignant perivascular epithelioid cell neoplasm in the liver: report of a pediatric case) . Surgical Case Reports7 1 of 11 - 11 of 11 2021.9Reviewed

Language：English Publisher：Springer Berlin Heidelberg

症例は10歳男児で、1ヵ月前から高熱が続いており、血液検査でCRP高値を認めたため精査目的に前医を受診した。腹部超音波検査では肝に大型固形腫瘍を認め、造影CTで肝S4とS5に局在する腫瘍がみられ、MRIではT1強調像で低信号、T2強調像で高信号を呈し、18F-FDG-PETにてFDGの著明な取り込みがみられた。AFP、PIVKA-II、CEA、CA19-9はいずれも正常範囲内にあり、未分化癌疑いにて手術目的に当院紹介となった。コア針生検を施行したところ肝細胞癌が疑われ、術前の造影CTでは腫瘍サイズの著明な増大が生じていた。開腹下に腫瘍切除を行い、術中所見では大型腫瘍は肝中心部に位置しており、腹膜播種や腹腔内転移は認めなかった。胆嚢切除後に肝実質を切離し、S8背側は温存した。切除標本の肉眼所見では出血と壊死を伴った黄白色の10×9cm大の腫瘍であり、境界明瞭であったが腫瘍細胞に浸潤性増殖パターンと脈管浸潤がみられ、血管周囲の多角形ないし楕円形細胞を呈し、束状配列の紡錘細胞、淡明な細胞質を有する円形類上皮細胞が認められた。また、免疫組織化学染色では細胞の一部はα-SMAとメランAに陽性を示しており、血管周囲類上皮細胞腫瘍(PEComa)と診断した。術後6ヵ月、肩関節痛を訴え、生検にてPEComaの骨転移と診断、化学療法後に脊椎切除術を施行した。その2年後に骨盤転移と肺転移をきたして転移巣に対する手術を行い、さらに骨盤転移を認めたためmTOR阻害剤にて治療中である。

松下裕亮, 上笹貫太郎, 平木翼, 谷本昭英, 坂本泰二 . 20年前に迷入したと考えられる涙嚢内異物の1例 . あたらしい眼科38 ( 9 ) 1123 - 1126 2021.9Reviewed

Language：Japanese Publisher：(株)メディカル葵出版

外傷時に迷入したと考えられる涙嚢内異物の症例を報告する。症例は34歳、男性。約20年前に左眼下涙点付近を竹で受傷した既往がある。受傷後から慢性的に左鼻汁を自覚していた。最近になって左眼の眼脂を自覚し、近医で涙道閉塞を疑われ当科へ紹介となった。初診時に左眼内眼角部に外傷の痕跡はなかった。通水検査で左側の通水を認めなかった。単純CT検査を行ったところ左眼涙嚢内に10mm大で高信号の棒状陰影を認めた。涙道内視鏡検査では左眼涙嚢内の異物が疑われた。涙道内視鏡による摘出は困難と考え涙嚢鼻腔吻合術(DCR)鼻内法を行った。摘出した異物は、病理組織学的検査で放線菌が全周に付着した植物片と診断された。術直後より左眼の眼脂は消失し、通水は改善した。異物は涙小管や鼻涙管の通過が困難な大きさであり、また外傷の既往があることから、受傷時に涙嚢内へ迷入したものと考えられた。大型の涙嚢内異物であったがDCR鼻内法で抽出が可能であった。(著者抄録)

Rakan Kotoku, Shintaro Yanazume, Takafumi Kuroda, Yusuke Kobayashi, Ikumi Kitazono, Toshiaki Akahane, Akihide Tanimoto, Hiroaki Kobayashi . Two Components of Variant Profiles in Primary Vaginal Carcinosarcoma via Next-Generation Sequencing and a Literature Review. . International journal of surgical pathology30 ( 3 ) 10668969211037915 - 10668969211037915 2021.8Reviewed International journal

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

Primary vaginal carcinosarcoma (VCS) is an extremely rare and aggressive tumor consisting of admixed malignant epithelial and mesenchymal elements. We report a case of VCS that was subjected to analysis by immunohistochemistry and next-generation sequencing (NGS). A 53-year-old woman with post-menopausal vaginal bleeding underwent surgical excision followed by concurrent chemoradiation. A well demarcated tumor was growing in a discontinuous fashion at a location some distance from both the cervix and vulva. Microscopically, the tumor consisted of adenocarcinoma components and sarcoma components consisting of a sheet-like growth of spindle-shaped cells, and we diagnosed this tumor as primary vaginal carcinosarcoma. NGS analysis of each component identified the following variants, TP53, PIK3CA, KRAS and FBXW7. A comparison of microsatellite instability (MSI) and tumor mutation burden (TMB) showed that within both tissues the sarcomatous components had a higher MSI and TMB than the carcinomatous components. This case supports "a monoclonal theory" with the genome profile being similar to other malignant mixed Müllerian tumors.

DOI： 10.1177/10668969211037915

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古江惠理, 上笹貫太郎, 平木翼, 小牧祐雅, 東裕子, 谷本昭英, 井戸章雄, 坂本泰二 . 臨床報告眼窩内に寄生したマンソン孤虫症の1例 . 臨床眼科75 ( 8 ) 1031 - 1036 2021.8Reviewed

Toshiaki Akahane, Ikumi Kitazono, Yusuke Kobayashi, Yukari Nishida-Kirita, Tomomi Yamaguchi, Shintaro Yanazume, Kazuhiro Tabata, Hiroaki Kobayashi, Akihide Tanimoto . Direct next-generation sequencing analysis using endometrial liquid-based cytology specimens for rapid cancer genomic profiling. . Diagnostic cytopathology49 ( 9 ) 1078 - 1085 2021.7Reviewed International journal

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

BACKGROUND: Genomic examination of cytology specimens is often performed on cell blocks or conventional smears rather than on liquid-based cytology (LBC) specimens. Since LBC specimens preserve high-quality DNA, cancer genome profiling using next-generation sequencing (NGS) is also attainable from residual LBC specimens. One of the advantages of using LBC specimens for NGS is that it allows direct extraction of DNA from residual specimens, avoiding a sacrifice of smear slides and minimizing genomic profiling processing time. METHODS: Endometrial LBC specimens were subjected to NGS analysis to validate the practicality of rapid cancer genomic profiling in a pathology laboratory. The extracted DNA was subjected to NGS using a customized cancer gene panel comprising 56 genes and 17 microsatellite regions. The workflow strategy was defined, and the processing time estimated for specimen sampling, cell counting, NGS run, and genome profiling. RESULTS: NGS analysis of most LBC specimens revealed somatic mutations, tumor mutation burden, and microsatellite instability, which were almost identical to those obtained from formalin-fixed paraffin-embedded tissues. The processing time for direct NGS analysis and cancer genomic profiling of the residual LBC specimens was approximately 5 days. CONCLUSION: The residual LBC specimens collected using endometrial cytology were verified to carry a high tumor fraction for NGS analysis and could serve as an alternate source for rapid molecular classification and diagnosis of endometrial cancers, as a routine process in a pathology laboratory.

DOI： 10.1002/dc.24841

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Mari Kirishima, Ikuma Kato, Masanori Hisaoka, Yukio Nakatani, Aya Harada Takeda, Keiko Mizuno, Akihide Tanimoto . Solid endobronchial tumor with EWSR1-FLI1 fusion gene - A diagnostically challenging case of the Ewing sarcoma. . Pathology international71 ( 7 ) 488 - 490 2021.7Reviewed International journal

Tasaki Takashi, Hatanaka Kazuhito, Kitazono Ikumi, Noguchi Hirotsugu, Tabata Kazuhiro, Higashi Michiyo, Maeda Kouki, Yokose Tomoyuki, Uekusa Toshimasa, Tanimoto Akihide . サルコイドーシスの血管病変によって引き起こされた肺梗塞　症例報告(Pulmonary infarction caused by sarcoidosis vascular involvement: A case report) . Pathology International71 ( 7 ) 480 - 484 2021.7Reviewed

Language：English Publisher：John Wiley & Sons Australia, Ltd

症例は60歳女性で、喀血を主訴とした。喀血は手術の5ヵ月前から始まり、2ヵ月間断続的に続いていた。血管炎や膠原病を示唆する皮膚病変や関節痛などの徴候はなく、関節リウマチや他の膠原病の既往歴もなかった。臨床検査では、血清アンジオテンシンI変換酵素や血清腫瘍マーカーが正常で、細菌、真菌、マイコバクテリウムも全て陰性であった。造影剤を用いた胸部CTでは、右上葉に気管支閉塞と無気肺様の腫瘤が認められ、両側の上葉には気管支や肺血管に沿って小さな結節が認められた。顕著な肺門リンパ節腫脹は認められなかった。18F-FDG PET/CTでは、右上葉の無気肺様腫瘤にFDGの取り込みが増加していた。肺癌との臨床診断の下、右上葉切除およびS6区域切除術を実施した。肉眼検査で、臓側胸膜の下に境界明瞭な暗褐色の領域が認められ、組織学的検査により、暗褐色の部分は古い梗塞であり、出血、ヘモシデローシス、線維化、軽度のリンパ球浸潤から構成されていた。弾性肺動脈では肉芽腫が副膜と中膜に浸潤し、弾性線維の崩壊と破壊を起こしていた。梗塞部位の端には肉芽腫による動脈閉塞が認められ、動脈サルコイドーシスの肉芽腫浸潤が肺梗塞の原因であると考えられた。

Masayoshi Otake, Hiroaki Kawaguchi, Satoko Enya, Akihisa Kangawa, Tadashi Koga, Kei Matsuo, Sohsuke Yamada, Md Mahfuzur Rahman, Naoki Miura, Masatoshi Shibata, Akihide Tanimoto . High Pathological Reproducibility of Diet-induced Atherosclerosis in Microminipigs via Cloning Technology. . In vivo (Athens, Greece)35 ( 4 ) 2025 - 2033 2021.7Reviewed International journal

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

BACKGROUND/AIM: The reproducibility of athero - sclerotic lesions was evaluated after the production of cloned-microminipigs and their offspring. MATERIALS AND METHODS: Cloned-microminipig-parents were produced by microminipigsomatic cell nuclei. These parents were crossbred and delivered males (F1-offspring) were divided into two groups: normal chow diet (NcD)-fed and high-fat/high-cholesterol diet (HcD)-fed groups. One of the F1-offsprings was subjected to cloning, and delivered males (F1-clones) were fed with HcD. After 8 weeks, all animals were necropsied for patho - physiological studies compared to non-cloned-microminipigs. RESULTS: HcD-fed F1-offspring and F1-clones, but not NcD-fed F1-offspring, exhibited increased serum lipid levels and systemic atherosclerosis, which were comparable to those of HcD-fed non-cloned-microminipigs. Homogeneity of variance analysis demonstrated that standard deviation values of serum lipoprotein and aortic atherosclerosis area from HcD-fed animals decreased in F1-offspring and F1-clones. CONCLUSION: HcD-induced atherogenesis was highly reproducible in F1-offsprings and F1-clones, indicating that the atherosclerosis-prone genomic background was preserved in the cloned-microminipigs, which can be used for studies on human atherosclerosis and related diseases.

DOI： 10.21873/invivo.12471

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Yusuke Torikai, Yuji Sasaki, Keita Sasaki, Akifumi Kyuno, Shunji Haruta, Akihide Tanimoto . Evaluation of Systemic and Mucosal Immune Responses Induced by a Nasal Powder Delivery System in Conjunction with an OVA Antigen in Cynomolgus Monkeys. . Journal of pharmaceutical sciences110 ( 5 ) 2038 - 2046 2021.5Reviewed International journal

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

An immune response for a nasal ovalbumin (OVA) powder formulation with an applied nasal delivery platform technology, consisting of a powdery nasal carrier and a device, was evaluated in monkeys with similar upper respiratory tracts and immune systems to those of humans, in order to assess the applicability to a vaccine antigen. Nasal distribution and retention studies using a 3D nasal cavity model and manganese-enhanced MRI were conducted by administering nasal dye and manganese powder formulations with the applied technology. Systemic and mucosal immune responses for the nasal OVA powder formulation were evaluated by determining serum IgG and nasal wash IgA antibody titers. The nasal dye and manganese powder formulations showed wider distribution and longer retention time than did a nasal liquid formulation. The nasal OVA powder formulation also showed comparable and higher antigen-specific IgG antibody titer to an injection and nasal liquid formulation, respectively. Furthermore, antigen-specific IgA antibody response was detected only for the nasal OVA powder formulation. The present study suggests that the technology, originally designed for drug absorption, is promising for nasal vaccines, enabling both a mucosal immunity response as the first line of defense and systemic immunity response as a second line of defense against infection.

DOI： 10.1016/j.xphs.2020.11.023

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米澤大, 比嘉那優大, 内田裕之, 赤羽俊章, 横山勢也, 霧島茉莉, 平木翼, 谷本昭英, 吉本幸司 . 脳腫瘍に特化したがん遺伝子パネル検査の実臨床における有用性 . Brain Tumor Pathology38 ( Suppl. ) 073 - 073 2021.5

赤羽俊章, 比嘉那優大, 霧島茉莉, 内田裕之, 米澤大, 坂本一平, 野原祥夫, 吉本幸司, 谷本昭英 . 神経膠腫診断用パネル検査で見つかった新規EGFR variantを有する神経膠腫の病理組織学的特徴 . Brain Tumor Pathology38 ( Suppl. ) 073 - 073 2021.5

比嘉那優大, 赤羽俊章, 米澤大, 内田裕之, 藤尾信吾, 横山勢也, 霧島茉莉, 濱田大治, 谷本昭英, 吉本幸司 . 日本人のhigh grade glioma患者における遺伝子変異の特徴 . Brain Tumor Pathology38 ( Suppl. ) 074 - 074 2021.5

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