猪口　淳一 (イノクチ　ジュンイチ)

Inokuchi Junichi

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教授
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  • 専任   琉球大学   医学研究科   教授  

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  • Field experiment of a telesurgery system using a surgical robot with haptic feedback.

    Ota M, Oki E, Nakanoko T, Tanaka Y, Toyota S, Hu Q, Nakaji Y, Nakanishi R, Ando K, Kimura Y, Hisamatsu Y, Mimori K, Takahashi Y, Morohashi H, Kanno T, Tadano K, Kawashima K, Takano H, Ebihara Y, Shiota M, Inokuchi J, Eto M, Yoshizumi T, Hakamada K, Hirano S, Mori M

    Surgery today ( Surgery Today )  54 ( 4 ) 375 - 381   2024年04月 [ 査読有り ]

    掲載種別: 研究論文（学術雑誌）

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    Purpose: To verify the usefulness of haptic feedback in telesurgery and improve the safety of telerobotic surgery. Methods: The surgeon's console was installed at two sites (Fukuoka and Beppu; 140 km apart), and the patient cart was installed in Fukuoka. During the experiment, the surgeon was blinded to the haptic feedback levels and asked to grasp the intestinal tract in an animal model. The surgeon then performed the tasks at each location. Results: No marked differences in task accuracy or average grasping force were observed between the surgeon locations. However, the average task completion time was significantly longer, and the system usability scale (SUS) was significantly lower rating for remote operations than for local ones. No marked differences in task accuracy or task completion time were observed between the haptic feedback levels. However, with haptic feedback, the organ was grasped with a significantly weaker force than that without it. Furthermore, with haptic feedback, experienced surgeons in robotic surgery tended to perform an equivalent task with weaker grasping forces than inexperienced surgeons. Conclusion: The haptic feedback function is a tool that allows the surgeon to perform surgery with an appropriate grasping force, both on site and remotely. Improved safety is necessary in telesurgery; haptic feedback will thus be an essential technology in robotic telesurgery going forward.

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  • The Role of Adipocytokines and their Receptors in Prostate Cancer: Adiponectin May Protect Against Progression.

    Kashiwagi E, Kawahara T, Kinoshita F, Shiota M, Inokuchi J, Miyamoto H, Eto M

    Anticancer research ( Anticancer Research )  44 ( 4 ) 1369 - 1376   2024年04月 [ 査読有り ]

    掲載種別: 研究論文（学術雑誌）

    　概要を見る

    Background/Aim: Obesity is correlated with an increased risk of developing malignancies, including prostate cancer. Adipocytokines, such as leptin and adiponectin, are a family of hormones derived from adipose tissue that are involved not only in metabolism, but also in the development and progression of various malignancies. However, little is known about their role in prostate cancer. This study aimed to determine how leptin, adiponectin, and their receptors impact the spread of prostate cancer. Materials and Methods: We first performed immunohistochemical analysis of prostate cancer tissue microarrays to detect leptin, leptin receptor (Ob-R), adiponectin, and adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2). Wound healing assays and western blot analysis were then performed in human prostate cancer cell lines. Results: Immunohistochemistry showed that prostate tissue was not significantly positive for adiponectin. However, its expression tended to decrease according to the International Society of Urological Pathology (ISUP) grade of prostate cancer (p=0.056). In prostate cancer cell lines, administration of the synthetic adiponectin AdipoRon suppressed cell migration as well as the expression of phospho-NF-κB and cyclooxygenase-2, whereas leptin stimulated these effects. Conclusion: Adiponectin expression tended to be suppressed according to ISUP grade in prostate cancer tissues. In vitro, tumor cell migration was induced by leptin but suppressed by adiponectin. Targeting adipocytokines could be a novel treatment strategy for prostate cancer.

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  • Validation of schedules for optimal prostate-specific antigen monitoring after radical prostatectomy.

    Blas L, Shiota M, Tanegashima T, Tsukahara S, Ueda S, Mutaguchi J, Goto S, Kobayashi S, Matsumoto T, Inokuchi J, Eto M

    International journal of urology : official journal of the Japanese Urological Association ( International Journal of Urology )  31 ( 4 ) 404 - 408   2024年04月 [ 査読有り ]

    掲載種別: 研究論文（学術雑誌）

    　概要を見る

    Background: Early detection of biochemical recurrence (BCR) after radical prostatectomy (RP) is crucial for early treatment and improving survival outcomes. The optimal prostate-specific antigen (PSA) monitoring remains unclear, and several models have been proposed. We aimed to externally validate four models for optimal PSA monitoring after RP and propose modifications to improve them. Methods: We reviewed the clinicopathological data of 896 patients who underwent robot-assisted RP between 2009 and 2022. We examined all PSA values and estimated the PSA value for four monitoring schedules at each time point in the virtual follow-up. We defined the ideal PSA for BCR detection between 0.2 and 0.4 ng/mL. Results: During the median follow-up of 21.4 months, 128 (14.3%) patients presented BCR. The original and modified Keio models, National Cancer Center Hospital model, and American Urological Association/American Society for Radiation Oncology model detected BCR in 14 (10.9%), three (2.3%), 12 (9.4%), and 11 (8.6%) patients with PSA >0.4 ng/mL. Most patients experienced BCR detected with PSA >0.4 ng/mL during the first year postoperative. The modification of interval within 6 months postoperative avoided BCR detection with PSA >0.4 ng/mL within the first year postoperative in 8/9 (88.9%), 1/2 (50.0%), 5/6 (83.3%), and 4/4 (100%) for the original and modified Keio models, National Cancer Center Hospital model, and American Urological Association/American Society for Radiation Oncology model, respectively. Conclusion: We validated four models for PSA monitoring after RP to detect BCR and suggested modifications to avoid detections out of the desired range of PSA. These modifications could help to establish an optimal PSA monitoring schedule after RP.

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  • Treatment patterns and prognosis in patients with Bacillus Calmette-Guérin-exposed high-risk non-muscle invasive bladder cancer: a real-world data analysis.

    Nishimura N, Miyake M, Iida K, Miyamoto T, Tomida R, Numakura K, Inokuchi J, Yoneyama T, Okajima E, Yajima S, Masuda H, Terada N, Taoka R, Kobayashi T, Kojima T, Matsui Y, Nishiyama N, Kitamura H, Nishiyama H, Fujimoto K

    World journal of urology ( World Journal of Urology )  42 ( 1 ) 185   2024年03月 [ 査読有り ]

    掲載種別: 研究論文（学術雑誌）

    　概要を見る

    Purpose: The International Bladder Cancer Group designated the subgroup that is resistant to Bacillus Calmette–Guérin (BCG) but does not meet the criteria for BCG-unresponsive NMIBC as “BCG-exposed high-risk NMIBC” to guide optimal trial design. We aimed to investigate the treatment patterns and prognoses of patients with BCG-exposed NMIBC. Methods: We conducted a retrospective chart review of 3283 patients who received intravesical BCG therapy for NMIBC at 14 participating institutions between January 2000 and December 2019. Patients meeting the criteria for BCG-exposed and BCG-unresponsive NMIBC, as defined by the Food and Drug Administration and International Bladder Cancer Group, were selected. To compare treatment patterns and outcomes, high-risk recurrence occurring more than 24 months after the last dose of BCG was defined as “BCG-treated NMIBC.” In addition, we compared prognoses between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. Results: Of 3283 patients, 108 (3.3%), 150 (4.6%), and 391 (11.9%) were classified as having BCG-exposed, unresponsive, and treated NMIBC, respectively. BCG-exposed NMIBC demonstrated intermediate survival curves for intravesical recurrence-free and progression-free survival, falling between those of BCG-unresponsive and treated NMIBC. Among patients with BCG-exposed NMIBC, 48 (44.4%) received BCG rechallenge, which was the most commonly performed treatment, and 19 (17.6%) underwent early cystectomy. No significant differences were observed between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. Conclusions: The newly proposed definition of BCG-exposed NMIBC may serve as a valuable disease subgroup for distinguishing significant gray areas, except in cases of BCG-unresponsive NMIBC.

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  • Prognostic impact of histological discordance between transurethral resection and radical cystectomy.

    Matsuda A, Taoka R, Miki J, Saito R, Fukuokaya W, Hatakeyama S, Kawahara T, Fujii Y, Kato M, Sazuka T, Sano T, Urabe F, Kashima S, Naito H, Murakami Y, Miyake M, Daizumoto K, Matsushita Y, Hayashi T, Inokuchi J, Sugino Y, Shiga K, Yamaguchi N, Iio H, Yasue K, Abe T, Nakanishi S, Matsumura M, Fujii M, Nishihara K, Matsumoto H, Tatarano S, Wada K, Sekito S, Maruyama R, Nishiyama N, Nishiyama H, Kitamura H, Matsui Y, Japanese Urological Oncology Group

    BJU international ( BJU International )    2024年02月 [ 査読有り ]

    掲載種別: 研究論文（学術雑誌）

    　概要を見る

    Objective: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. Patients and methods: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. Results: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil–lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). Conclusion: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil–lymphocyte ratio and pathological stage were independent prognostic factors for OS.

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  • 新規尿中がんバイオマーカーを用いた簡易型センサデバイスの開発と臨床的有用性検討

    基盤研究(C)

    課題番号: 23K11898

    研究期間: 2023年04月  -  2026年03月 

    代表者: 猪口 淳一, 村田 正治, 姜 貞勲, 河野 喬仁, 松元 崇 

    直接経費: 3,600,000（円）  間接経費: 4,680,000（円）  金額合計: 1,080,000（円）

  • 機能性ナノ分子によるマクロファージ機能変換と慢性腎臓病の治療

    基盤研究(B)

    課題番号: 22H03968

    研究期間: 2022年04月  -  2025年03月 

    代表者: 姜 貞勲, 猪口 淳一, 村田 正治, 戸井田 力 

    直接経費: 10,200,000（円）  間接経費: 13,260,000（円）  金額合計: 3,060,000（円）

    　概要を見る

    IL-10修飾ナノ分子（抗炎症性サイトカインIL-10をナノ分子本体に修飾したもの）による治療効果における分子メカニズムを理解するために、IL-10修飾ナノ分子の受容体の同定を行った。ナノ分子本体（IL-10非修飾）にあるホスファチジルセリン（PS）がマクロファージ細胞を認識する重要な分子であると判断し、PS受容体の一種であるTim4を標的とした阻害実験を実施した。抗Tim4抗体の存在下では、マクロファージ細胞によるIL-10修飾ナノ分子の貪食量が有意に減少することを確認した。一方、ナノ分子に修飾されたIL-10はPS受容体との結合に影響を与えなかった。これらの結果から、IL-10修飾ナノ分子はIL-10によるSTAT3の刺激に加え、PS受容体の下流に存在するSTAT3を同時に刺激することで、相乗的に抗炎症効果を上げることが分かった。 また、長時間の高脂肪食給餌による腎傷害とIL-10修飾ナノ分子の投与による改善効果を検証した。高脂肪食給餌マウスは通常食給餌マウスに比べて糸球体（glomerulus）のサイズが有意に拡大することを確認した。高脂肪食給餌マウスにIL-10修飾ナノ分子とPBSを投与した場合、IL-10修飾ナノ分子投与群はPBS投与群に比べ、糸球体の肥大を顕著に抑制することが確認できた。線維化組織は高脂肪食給餌により若干増加している傾向が見られたが、IL-10修飾ナノ分子投与による治療効果に加え、より詳細な検討が必要であると判断した。さらに、PAS染色や、尿細管の傷害マーカーによる免疫染色を行い、尿細管の膨張と傷害に対する治療効果を入念に確認する必要があり、引き続き検討する予定である。

  • 尿中PKCαを標的とした新規尿路上皮がん診断システムの開発

    基盤研究(C)

    課題番号: 19K09692

    研究期間: 2019年04月  -  2022年03月 

    代表者: 猪口 淳一, 村田 正治, 姜 貞勲, 今田 憲二郎, 河野 喬仁 

    直接経費: 3,400,000（円）  間接経費: 4,420,000（円）  金額合計: 1,020,000（円）

    　概要を見る

    尿路上皮癌に対する尿中バイオマーカーは、その感度の低さからあまり利用されていないのが現状であるが、今回尿中の活性型プロテインキナーゼCα（PKCα）が尿路上皮癌に対し高い感度、特異度を示し、特に従来の検査法では感度が低かった低異型度腫瘍においても高い感度を示し、尿路上皮癌に対する新規尿中バイオマーカーとしての有用性が明らかとなった。さらに、より安価で簡便な検査法として、抗リン酸化ペプチド抗体を利用した電子バイオセンサを開発した。

  • 上部尿路がん早期発見を目的とした新規検査法の開発

    基盤研究(C)

    課題番号: 16K11010

    研究期間: 2016年04月  -  2019年03月 

    代表者: 猪口 淳一, 村田 正治, 片山 佳樹, 姜 貞勲, 清島 圭二郎 

    直接経費: 3,600,000（円）  間接経費: 4,680,000（円）  金額合計: 1,080,000（円）

    　概要を見る

    上部尿路がん（腎盂・尿管がん）の発がん因子として注目されているアリストロキア酸が、本邦でも発がんの原因となっているか検討した。台湾の上部尿路がん患者では高頻度でアルストロキア酸との関連が報告されたが、本邦の症例では非常に稀であることがわかった。 また、尿路上皮がんの新たな診断法として尿中の活性型リン酸化酵素Xの活性を測定したところ、尿路上皮がんの悪性度に関わらず高い感度、特異度を示し有望なバイオマーカーであることが示された。

  • Suwon, Korea 3次元培養モデルを用いた前立腺発癌機構の解析とバイオマーカーの検索

    若手研究(B)

    課題番号: 21791510

    研究期間: 2009年  -  2011年 

    代表者: 猪口 淳一 

    直接経費: 3,100,000（円）  間接経費: 4,030,000（円）  金額合計: 930,000（円）

    　概要を見る

    前立腺癌の発癌・増殖機構は未だに不明な点が多い。本研究では、より生体に近い実験系として3次元培養法を用いた解析を行い、前立腺発癌機構解析のための新たな解析手法を確立した。同手法により、アネキシンA1抑制によるIL-6を介した前立腺癌への関与を明らかにした。また、前立腺の正常な腺管形成にアンドロゲンレセプター(AR)が重要な役割を果たしていることをみいだし、ARの発現制御に関与する分子の機能解析をすることで前立腺癌への寄与を明らかにした。

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