竹内 啓 (タケウチ サトシ)

医学研究院 内科系部門 内科学分野助教
北海道大学病院助教
Last Updated :2025/06/10

■研究者基本情報

学位

  • 医学博士, 北海道大学

Researchmap個人ページ

研究分野

  • ライフサイエンス, 腫瘍診断、治療学

担当教育組織

■経歴

学歴

  • 2000年03月 - 現在, 北海道大学, 医学部, 医学科

■研究活動情報

論文

  • Factors and predictors affecting late external dose rates and isolation period in patients after lutetium-177-labeled DOTA-Tyr3-octreotate treatment for neuroendocrine tumors.
    Naoto Wakabayashi, Shiro Watanabe, Satoshi Takeuchi, Takahiro Tsuchikawa, Yamato Munakata, Kenji Hirata, Rina Kimura, Junki Takenaka, Hiroshi Ishii, Kohsuke Kudo
    Annals of nuclear medicine, 2025年04月05日, [国内誌]
    英語, 研究論文(学術雑誌), OBJECTIVE: In peptide receptor radionuclide therapy (PRRT) using lutetium-177-labeled DOTA-Tyr3-octreotate ([177Lu] DOTATATE), isolation is required until the external dose rate at 1 m (EDR-1 m) from the body surface falls below the regulatory standards of each country. While it is known that renal function influences EDR-1 m reduction within 180 min post-administration, the factors affecting EDR-1 m on the day following administration (Late EDR-1 m) remain unclear. This study aimed to identify factors influencing Late EDR-1 m after PRRT using [177Lu] DOTATATE for neuroendocrine tumors and to predict Late EDR-1 m using pretreatment [111In] pentetreotide single-photon emission computed tomography/computed tomography (SPECT/CT) data. METHODS: This study analyzed 111 PRRT cycles administered to 36 patients between September 2021 and August 2024. Late EDR-1 m was set as the dependent variable, whereas total radiopharmaceutical uptake (LUTtotal), dose per body weight, creatinine clearance (CCr), and albumin-bilirubin (ALBI) score were set as the independent variables in the multiple regression analysis. LUTtotal was calculated using SPECT/CT data acquired after the patient left the radiation therapy room, defining the volume of interest (VOI) as the area with SUVmean + 2SD or higher in the skeletal muscle. The VOI volume multiplied by the SUVmean was used to define LUTtotal. In addition, using [111In] pentetreotide SPECT/CT data, the total radiopharmaceutical uptake (OCTtotal) was calculated in a manner similar to LUTtotal, and its correlation with LUTtotal was examined. A predictive equation for Late EDR-1 m was developed using the results of the multivariate analysis, and its performance was tested using subsequent cases between August 2024 and January 2025. RESULTS: The median measured Late EDR-1 m was 8.0 (range, 4.0-26.0) μSv/h. LUTtotal and dose per body weight were significantly correlated with Late EDR-1 m, whereas CCr and ALBI scores were not. Based on the results of the multivariate analysis, the predictive equation using the dose per body weight, assuming a dosage of 7400 MBq and OCTtotal, achieved a root mean square error (RMSE) of 2.24 μSv/h. In subsequent test cases, the RMSE was 3.47 μSv/h. CONCLUSIONS: Late EDR-1 m is significantly correlated with LUTtotal and dose per body weight. It can be accurately predicted using [111In] pentetreotide SPECT/CT data.
  • Urinary Dopamine Levels Can Predict the Avidity of Post-Therapy [131I]MIBG Scintigraphy in Unresectable or Metastatic Pheochromocytomas and Paragangliomas: A Preliminary Clinical Study
    Junki Takenaka, Shiro Watanabe, Takashige Abe, Satoshi Takeuchi, Kenji Hirata, Rina Kimura, Hiroshi Ishii, Naoto Wakabayashi, Mungunkhuyag Majigsuren, Kohsuke Kudo
    Pharmaceuticals, 18, 2, 165, 165, MDPI AG, 2025年01月26日
    研究論文(学術雑誌), Background/Objectives: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that produce catecholamines. Unresectable or metastatic PPGLs are treated with [131I]metaiodobenzylguanidine (MIBG), but MIBG avidity is often heterogeneous. Identifying predictive factors for non-avid lesions on scintigraphy is clinically important. The primary objective of this study was to investigate the relationship between MIBG avidity and catecholamine secretion patterns in patients with unresectable or metastatic PPGLs. Methods: This retrospective study included 27 patients treated with [131I]MIBG for unresectable/metastatic PPGLs between 2001 and 2024. Patients received a single intravenous dose of [131I]MIBG (5.5–7.4 GBq), with post-therapy scintigraphy performed 3–7 days later. Non-avid lesions were assessed by imaging and confirmed using CT, MRI, and FDG-PET. Clinical factors, including age, sex, prior treatments, metastasis sites, and urine catecholamines, were evaluated using univariate logistic analysis. Predictive factors were assessed via receiver operating characteristic curves. Results: Non-avid lesions were found in nine patients (33.3%). These patients were younger (median age 38 vs. 62.5 years) and had higher urine dopamine levels (median 1510 vs. 779 μg/day) than those without non-avid lesions. Younger age (odds ratio: 0.892, p < 0.01) and higher urinary dopamine levels (odds ratio: 1.003, p < 0.01) were significantly associated with non-avid lesions. All patients > 45 years with urinary dopamine < 1190 μg/day had no non-avid lesions, whereas patients < 45 years with urinary dopamine > 1190 μg/day had non-avid lesions. Conclusions: Age and urinary dopamine levels may predict non-avid lesions in unresectable/metastatic PPGLs, aiding treatment decisions for [131I]MIBG therapy. This article is a revised and expanded version of a paper entitled “Urine dopamine level and age can predict non-avid lesion on scintigraphy after I-131 MIBG treatment for unresectable/metastatic PPGL”, which was presented at SNMMI 2024, Toronto, from 8 June to 11 June 2024.
  • Actionable Gene Alterations Identified in Patients With Malignant Melanoma by Targeted Sequencing in Japan.
    Takuro Noguchi, Shin Ariga, Rika Moku, Junko Kikuchi, Toraji Amano, Takuya Maeda, Kosuke Ishikawa, Taku Maeda, Akihiko Shiiya, Tomohiro Goda, Yoshihito Ohhara, Kanako Hagio, Yusuke Saito, Kanako C Hatanaka, Yutaka Hatanaka, Jun Taguchi, Satoshi Takeuchi, Yasushi Shimizu, Ichiro Kinoshita
    JCO precision oncology, 9, e2400437, 2025年01月, [国際誌]
    英語, 研究論文(学術雑誌), PURPOSE: Precision medicine plays an important role in the treatment of patients with advanced melanoma. Despite its high incidence in White patients, advanced melanoma is rare in Asian countries, hampering prospective clinical trials targeting the Asian population. This retrospective study aimed to elucidate the real-world molecular diagnoses and outcomes of Japanese patients with melanoma using comprehensive genome profiling (CGP). MATERIALS AND METHODS: Patients with melanoma who completed standard anticancer medical treatments (including those expected to complete the treatments) underwent CGP, which is covered by the National Health Insurance. We analyzed the results and clinical annotations of 569 patients registered before August 2023 in a national database. RESULTS: Skin, mucosal, and uveal melanomas accounted for 64%, 28%, and 7% of cases, respectively. Patients with BRAF, NRAS, NF1, and KIT variants represented 25%, 20%, 17%, and 17%, respectively. Eighty-two percent of BRAF, 97% of NRAS, 69% of NF1, and 54% of KIT were actionable alterations (ie, BRAF classes I, II, and III, NRAS Q61, G12, G13, NF1 loss-of-function, KIT gain-of-function variants). BRAF V600E/K variants occurred in 22% of skin and 2% of mucosal melanomas, but not in uveal melanomas. The mean tumor mutation burden in cutaneous melanomas was 4.2 variants/Mb. Patients previously treated with BRAF-targeted therapy harbored amplifications of BRAF and cell cycle genes more frequently than therapy-naive patients. Thirty-six patients (6.3%) were treated following the molecular tumor board (MTB) recommendations. CONCLUSION: Actionable gene alterations in BRAF, NRAS, NF1, and KIT are common in Japanese patients with melanoma. However, few patients were treated according to the MTB recommendations, suggesting that there is an unmet need to increase accessibility to gene-matched clinical trials in Japan.
  • Initial validation of the clinical significance of the NETest in Japanese gastroenteropancreatic neuroendocrine tumor patients.
    Hao Zhang, Takahiro Tsuchikawa, Satoshi Takeuchi, Kenji Hirata, Kimitaka Tanaka, Aya Matsui, Yoshitsugu Nakanishi, Toshimichi Asano, Takehiro Noji, Toru Nakamura, Shintaro Takeuchi, Masataka Wada, Satoshi Hirano
    Endocrine journal, 71, 9, 873, 880, 2024年09月02日, [国内誌]
    英語, 研究論文(学術雑誌), As novel biomarkers for gastroenteropancreatic neuroendocrine tumors (GEPNET) are in demand, we aimed to validate the clinical value of the NETest in Japanese patients. Between 2021 and 2023, blood and clinical data were collected from patients with GEPNET. Among 35 patients (median age: 59 [49-66] years), 27 cases originated from the pancreas and eight from the gastrointestinal tract. Of 69 samples sent to the laboratory, 56 (81.2%) underwent NETest. The diagnostic sensitivity was 97.1%. Among three patients who underwent R0 resection and four treated with peptide receptor radionuclide therapy, the changes in NETest scores closely correlated with disease progression. The NETest demonstrated high diagnostic efficacy and accurate therapeutic monitoring capabilities in a Japanese population.
  • Distinct clinicopathological features of neuroendocrine liver metastases originating from the pancreas and rectum.
    Hao Zhang, Takahiro Tsuchikawa, Satoshi Takeuchi, Hang Deng, Kimitaka Tanaka, Aya Matsui, Yoshitsugu Nakanishi, Toshimichi Asano, Takehiro Noji, Toru Nakamura, Shintaro Takeuchi, Masataka Wada, Jian Xu, Yu Zhang, Satoshi Hirano
    World journal of surgical oncology, 22, 1, 209, 209, 2024年08月03日, [国際誌]
    英語, 研究論文(学術雑誌), INTRODUCTION: Survival comparisons among patients with liver metastases from pancreatic and rectal neuroendocrine tumors (NETs) were limited, and the efficacy of observation rules in patients undergoing hepatectomy for neuroendocrine liver metastases (NELMs) was unknown. This study aims to distinguish these characteristics and clarify the effects of the observation rules on NELMs. METHODS: Clinical data were separately collected from patients with pancreatic and rectal NELMs at medical centers in both Japan and China. The Japanese cohort followed the observation rules for the resection of NELMs. A comparative analysis was conducted on clinical characteristics and prognosis features such as overall survival time (OS) and disease-free survival interval (DFS-I). RESULTS: Enrollment included 47 and 34 patients from Japan and China, respectively. Of these, 69 and 12 patients had tumors originating from the pancreas and rectum, respectively. The OS time in patients undergoing primary tumor resection was significantly longer; however, the OS time between the patients undergoing and not undergoing radical resection of liver metastasis was the same. In asynchronous NELMs, patients with rectal (R)-NELMs showed a significantly higher proportion of type III NELMs. Additionally, the median DFS-I of asynchronous R-NELMs was longer than the recommended follow-up time, with 71.4% of them classified as G2. In the Japanese cohort, patients who adhered to the observation rules exhibited a longer median DFS after hepatectomy for NELMs compared with their counterparts. CONCLUSION: Although curative surgery is crucial for primary lesions, personalized approaches are required to manage NELMs. Extended overall follow-ups and shortened follow-up intervals are recommended for G2 stage rectal NETs. The observation rules for NELMs require further validation with a larger sample size.
  • 切除不能/転移性PPGLにおけるI-131 MIBG治療後シンチグラフィーで非集積病変を有する患者の予測因子に関する検討               
    竹中 淳規, 渡邊 史郎, 安部 崇重, 土川 貴裕, 竹内 啓, 平田 健司, 木村 理奈, 若林 直人, 篠原 信雄, 工藤 與亮
    日本内分泌外科学会雑誌, 41, Suppl.1, S202, S202, (一社)日本内分泌外科学会, 2024年04月
    日本語
  • 神経内分泌腫瘍に対するLu-177 DOTATATE治療における投与翌日の体外線量率に影響を与える因子に関する検討               
    若林 直人, 渡邊 史郎, 竹内 啓, 土川 貴裕, 平田 健司, 木村 理奈, 竹中 淳規, 石井 宙史, 南部 敏和, 工藤 與亮
    核医学, 61, Suppl., S157, S157, (一社)日本核医学会, 2024年
    日本語
  • 切除不能/転移性PPGLにおけるMIBG治療前のFDG-PETの集積性に関する検討               
    竹中 淳規, 渡邊 史郎, 安部 崇重, 土川 貴裕, 竹内 啓, 平田 健司, 木村 理奈, 石井 宙史, 若林 直人, 工藤 與亮
    核医学, 61, Suppl., S169, S169, (一社)日本核医学会, 2024年
    日本語
  • Predictive factors of early FDG-PET response to [131I] MIBG treatment for unresectable or metastatic pheochromocytomas and paragangliomas (PPGLs).
    Junki Takenaka, Shiro Watanabe, Takashige Abe, Takahiro Tsuchikawa, Satoshi Takeuchi, Kenji Hirata, Rina Kimura, Naoto Wakabayashi, Nobuo Shinohara, Kohsuke Kudo
    Neuroendocrinology, 2023年09月19日, [国際誌]
    英語, 研究論文(学術雑誌), Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours that produce catecholamines. [131I] MIBG-avid unresectable or metastatic PPGLs are treated with [131I] MIBG therapy. A high metabolic tumour volume (MTV) and total lesion glycolysis (TLG) can be poor prognostic factors. Therefore, we evaluated the metabolic responses to [131I] MIBG therapy with respect to other clinical factors.A retrospective study was performed on a series of 20 patients who underwent FDG-PET before and after [131I] MIBG therapy. We administered a single dose comprising 5.5 GBq of [131I] MIBG. Semi-quantitative parameters (SUVmax, MTV, and TLG) were calculated using the liver SUV (mean + 3SD) as a threshold on Metavol software. The semi-quantitative FDG-PET parameters for determining response were complete response , partial remission, stable disease, and progressive disease (PD). We divided our study participants into the PD and non-PD groups and compared the overall survival between the two groups. Subsequently, we evaluated the relationships between metabolic response and age, sex, tumour type, metastatic site, chemotherapy or external radiation history, and 24-hour urine catecholamine levels by univariate logistic regression analyses. Both MTV-based and TLG-based criteria for PD vs. non-PD were significant prognostic factors (p = 0.014). However, treatment response as evaluated based on the SUVmax was not a significant predictor. Higher urinary dopamine levels were associated with poor metabolic response as assessed by MTV and TLG. The other clinical parameters were non-significant. Poor metabolic response (measured with MTV and TLG) to [131I] MIBG therapy in unresectable or metastatic PPGLs was related to shorter OS. The poor metabolic response can be predicted using the urinary dopamine level.
  • Early prediction of treatment outcome for lenvatinib using 18F-FDG PET/CT in patients with unresectable or advanced thyroid carcinoma refractory to radioiodine treatment: a prospective, multicentre, non-randomised study.
    Satoshi Takeuchi, Kenji Hirata, Keiichi Magota, Shiro Watanabe, Rika Moku, Akihiko Shiiya, Jun Taguchi, Shin Ariga, Tomohiro Goda, Yoshihito Ohhara, Takurou Noguchi, Yasushi Shimizu, Ichiro Kinoshita, Rio Honma, Yasushi Tsuji, Akihiro Homma, Hirotoshi Dosaka-Akita
    EJNMMI research, 13, 1, 69, 69, 2023年07月17日, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Lenvatinib is widely used to treat unresectable and advanced thyroid carcinomas. We aimed to determine whether 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) performed 1 week after lenvatinib treatment initiation could predict treatment outcomes. RESULTS: This was a prospective, nonrandomised, multicentre study. Patients with pathologically confirmed differentiated thyroid carcinoma (DTC) and lesions refractory to radioiodine treatment were eligible for inclusion. Patients were treated with 24 mg lenvatinib as the initial dose and underwent PET/CT examination 1 week after treatment initiation. Contrast-enhanced CT was scheduled at least 4 weeks later as the gold standard for evaluation. The primary endpoint was to evaluate the discrimination power of maximum standardised uptake value (SUVmax) obtained by PET/CT compared to that obtained by contrast-enhanced CT. Evaluation was performed using the area under the receiver operating characteristic (ROC-AUC) curve. Twenty-one patients were included in this analysis. Receiver operating characteristic (ROC) curve analysis yielded an AUC of 0.714 for SUVmax after 1 week of lenvatinib treatment. The best cut-off value for the treatment response for SUVmax was 15.211. The sensitivity and specificity of this cut-off value were 0.583 and 0.857, respectively. The median progression-free survival was 26.3 months in patients with an under-cut-off value and 19.7 months in patients with an over-cut-off value (P = 0.078). CONCLUSIONS: The therapeutic effects of lenvatinib were detected earlier than those of CT because of decreased FDG uptake on PET/CT. PET/CT examination 1 week after the initiation of lenvatinib treatment may predict treatment outcomes in patients with DTC. TRIAL REGISTRATION: This trial was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (number UMIN000022592) on 6 June, 2016.
  • 切除不能/転移性PPGLにおける初回I-131MIBG治療による総糖代謝量の変化と予後の関係性の解析               
    竹中 淳規, 渡邊 史郎, 安部 崇重, 土川 貴裕, 竹内 啓, 平田 健司, 木村 理奈, 若林 直人, 篠原 信雄, 工藤 與亮
    核医学, 60, Suppl., S216, S216, (一社)日本核医学会, 2023年
    日本語
  • EGFR inhibition in EGFR-mutant lung cancer cells perturbs innate immune signaling pathways in the tumor microenvironment.
    Akihiko Shiiya, Takuro Noguchi, Utano Tomaru, Shin Ariga, Yuta Takashima, Yoshihito Ohhara, Jun Taguchi, Satoshi Takeuchi, Yasushi Shimizu, Ichiro Kinoshita, Tomonobu Koizumi, Yoshihiro Matsuno, Naofumi Shinagawa, Jun Sakakibara-Konishi, Hirotoshi Dosaka-Akita
    Cancer science, 2022年12月18日, [国際誌]
    英語, 研究論文(学術雑誌), Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) elicit potent cell cycle arrest in EGFR-mutant non-small-cell lung cancer (NSCLC) cells. However, little is known about the mechanisms through which these drugs alter the tumor phenotype that contributes to the immune escape of EGFR-mutant cells. Using EGFR-mutant NSCLC cell lines and tissue samples from patients, we investigated the changes in immune checkpoints expressed in tumor cells following EGFR inhibition. Subsequently, we also analyzed the role of soluble factors from the dying tumor cells in the activation of immune signaling pathways involved in therapy resistance. Upon EGFR-TKI treatment, we found that EGFR-mutant cells upregulated the expression of innate immune checkpoint CD24 in vitro. We then analyzed biopsy samples from six patients who developed resistance to a first-generation EGFR-TKI without the acquired T790M mutation. Immunohistochemistry revealed that levels of tumor CD24 expression were increased upon treatment compared with those from pre-treatment samples. Monocyte-derived macrophages facilitated antibody-dependent cellular phagocytosis when EGFR-TKI-treated EGFR-mutant cells were incubated with anti-CD24 antibodies in vitro, suggesting that CD24 may be a therapeutical target for EGFR-mutant lung cancer. Moreover, EGFR inhibition accelerated the release of cell-free DNA (cfDNA) from dying tumor cells, which activated the type I interferon signaling pathways in human THP-1 monocytes in a stimulator of interferon genes-dependent manner. Our study indicates that EGFR inhibition in EGFR-mutant NSCLC cells fosters a tumor microenvironment associated with immune escape. Thus, CD24 targeted therapy and cfDNA monitoring may contribute to improved treatment outcomes in patients with EGFR-mutant NSCLC.
  • Expression of karyopherin alfa 2 and karyopherin beta 1 correlate with poor prognosis in gastric cancer.
    Yoshihito Ohhara, Ichiro Kinoshita, Akira Suzuki, Makoto Imagawa, Jun Taguchi, Takuro Noguchi, Satoshi Takeuchi, Yasushi Shimizu, Hideyuki Seki, Junichi Suzuki, Hirotoshi Dosaka-Akita
    Oncology, 2022年10月21日, [国際誌]
    英語, 研究論文(学術雑誌), INTRODUCTION: Karyopherin alfa 2 (KPNA2) and karyopherin beta 1 (KPNB1), constitute nuclear transport protein complexes involved in nuclear import, and are significant in tumor progression. Although high KPNA2 expression was associated with poor prognosis in solid tumors, the relationship between KPNA2 and KPNB1 expression and their prognostic role in gastric cancer (GC) remains unclear. METHODS: Immunohistochemistry was used to correlate the expression of KPNA2 and KPNB1 with various features, including clinicopathologic characteristics in 130 patients with GC and survival in 94 patients with invasive lesions extending to the submucosa or deeper. RESULTS: High expression of KPNA2 and KPNB1 was found in 25% and 36% of the patients, respectively. Both were significantly related to tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, and Ki-67 expression. KPNA2 expression was significantly related to that of KPNB1 (P < 0.001). Patients with high KPNB1 expression had poorer prognosis than those with low expression (P = 0.027), as was also observed in case of KPNA2 (P < 0.001). Patients with high expression of both KPNA2 and KPNB1 accounted for 18% and had a poorer prognosis than those with high expression of either and those with low expression of both (P = 0.001). Multivariate analysis revealed that high expression of both KPNA2 and KPNB1 was an independent prognostic factor in patients with GC (HR 3.46, 95% CI 1.64-2.73, P = 0.001). CONCLUSION: KPNA2 expression was correlated with KPNB1 expression, and high co-expression of KPNA2 and KPNB1 may represent a strong prognostic biomarker in GC.
  • Risk Factor Analysis for the Occurrence of Severe Adverse Effects in Eribulin Treatment.
    Yoshitaka Saito, Yoh Takekuma, Takashi Takeshita, Takuro Noguchi, Satoshi Takeuchi, Yasushi Shimizu, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Mitsuru Sugawara
    Anticancer research, 42, 7, 3693, 3700, 2022年07月, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND/AIM: Eribulin is an effective chemotherapeutic agent for the treatment of metastatic breast cancer and advanced or metastatic soft-tissue sarcomas. However, severe adverse effects (SAEs) occur in 30-40% of the patients, and significantly reduce the patients' quality of life and disturb the recommended treatment schedules. Neutropenia is the main cause of treatment suspension, delay, and/or dose reductions, also leading to relative dose intensity reduction. This study aimed to examine the risk factors for SAE occurrence after eribulin treatment. PATIENTS AND METHODS: Eighty patients with metastatic breast cancer or advanced or metastatic soft tissue sarcoma who received eribulin were retrospectively evaluated. Risk factors for SAE occurrence in the first cycle were primarily assessed. In addition, factors associated with SAE occurrence during all treatment cycles were evaluated. RESULTS: SAEs in the first cycle occurred in 45% of patients. The primary SAE was neutropenia (91.7%). The incidence of SAEs during all treatment cycles was 61.3%. Multivariate analyses suggested that lower baseline neutrophil and hemoglobin levels were risk factors for SAE occurrence and severe neutropenia incidence in the first cycle. An independent factor associated with SAE occurrence during all cycles was age ≥65 years and a tendency was confirmed for baseline anemia. CONCLUSION: Baseline neutropenia and anemia were risk factors for SAE occurrence during the first eribulin treatment cycle. Age ≥65 years was also associated with SAE occurrence during all treatment cycles. Patients with these risk factors should be carefully monitored for assessment and prophylaxis.
  • Suitability of Oral Rehydration Solution (ORS) for Use in the Cisplatin Short Hydration Method.
    Yoshitaka Saito, Yoh Takekuma, Masaki Kobayashi, Naofumi Shinagawa, Takuro Noguchi, Satoshi Takeuchi, Yasushi Shimizu, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Mitsuru Sugawara
    Anticancer research, 42, 6, 3185, 3193, 2022年06月, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND/AIM: Short hydration is a method to change partial intravenous hydration to oral to administer cisplatin (CDDP); however, the most suitable form of oral hydration is unknown. This study aimed to determine whether oral rehydration solution (ORS) affects CDDP-induced nephrotoxicity (CIN) and electrolyte imbalance. PATIENTS AND METHODS: Lung cancer patients (n=200) who had received CDDP-including regimens (CDDP dosage ≥75 mg/m2) were retrospectively evaluated. We used logistic analysis to evaluate whether ORS intake could be a preventive factor for CIN (≥grade 2 serum creatinine elevation). Moreover, incidence of CIN and electrolyte imbalance and the variation in serum creatinine and electrolyte levels were compared between ORS and non-ORS (control) patients. RESULTS: CIN occurred in 9.8% of ORS patients, and 7.5% of non-ORS patients (p=0.79). The variation in serum creatinine level was also similar in both groups. Multivariate analysis suggested that ORS intake does not affect CIN, although CIN was associated with the coadministration of non-steroidal anti-inflammatory drugs and the presence of diabetes mellitus. The variations in serum electrolyte levels did not differ, and incidence of hyponatremia, hypokalemia, and hypochloremia was also similar between the groups. Moreover, patients in ORS group experienced significantly more anorexia compared to controls, and approximately 40% of the patients were unable to continue ORS intake. CONCLUSION: ORS intake in CDDP short hydration regimens does not affect CIN and CDDP-induced electrolyte imbalance; however, its intake is associated with the incidence of anorexia suggesting that ORS should not be used for oral hydration.
  • Long-term survival after repetitive lymphadenectomy for nodal recurrence of pancreatic neuroendocrine neoplasms: a report of two cases.
    Yuma Hane, Takahiro Tsuchikawa, Satoshi Takeuchi, Kimitaka Tanaka, Yoshitsugu Nakanishi, Toshimichi Asano, Takehiro Noji, Yo Kurashima, Yuma Ebihara, Soichi Murakami, Toru Nakamura, Keisuke Okamura, Toshiaki Shichinohe, Satoshi Hirano
    Journal of surgical case reports, 2021, 10, rjab446, 2021年10月, [国際誌]
    英語, Pancreatic neuroendocrine neoplasms (PNENs) are rare, but their incidence has increased in recent years. Curative surgery is recommended in several global guidelines for resectable PNENs. Lymph node recurrence after R0 resection for PNENs is infrequent, and global guidelines recommend surgical resection for recurrence, if resectable. However, data on the prognosis after surgical resection for nodal recurrence of PNENs are limited. We herein report two cases in which long-term survival was achieved after repetitive lymphadenectomy for nodal recurrence of PNENs. In both cases, the pathological findings for primary PNEN showed well-differentiated neuroendocrine neoplasms and R0 resection was successfully performed. The Ki-67 index increased with each resection in both cases. Both patients showed long-term survival (10 and 14 years, respectively). Repetitive lymphadenectomy for nodal recurrence of PNENs may improve patient prognosis.
  • Hepatectomy and immune checkpoint inhibitor treatment for liver metastasis originating from non-cutaneous melanoma: a report of three cases.
    Yoh Asahi, Toshiya Kamiyama, Tatshiko Kakisaka, Tatsuya Orimo, Shingo Shimada, Akihisa Nagatsu, Yuzuru Sakamoto, Takaya Ishikawa, Hirofumi Kamachi, Tomoko Mitsuhashi, Satoshi Takeuchi, Hirotoshi Dosaka-Akita, Akinobu Taketomi
    International cancer conference journal, 10, 4, 274, 279, 2021年10月, [国際誌]
    英語, The outcomes of hepatectomy alone for liver metastasis derived from non-cutaneous melanoma are insufficient, and the outcomes of systemic therapy alone are also insufficient, even since the development of immune checkpoint inhibitors (ICIs). We report the cases of three patients, in whom liver metastasis derived from non-cutaneous melanoma was treated with hepatectomy combined with ICI therapy, which was administered in various settings. One patient received ICI treatment for recurrent melanoma and survived 107 months after the first hepatectomy, one patient received both preoperative and adjuvant ICI treatment and has been disease-free for 27 months, and another patient received postoperative ICI treatment after reduction hepatectomy and has been alive with disease for 47 months. Since long-term survival is possible, hepatectomy combined with ICI therapy should be considered for the treatment of liver metastasis derived from non-cutaneous melanoma.
  • Severe hypertriglyceridemia induced by S-1: Subsequent case series of four patients and further review of the literature.
    Yoshitaka Saito, Yoh Takekuma, Satoshi Takeuchi, Yoshito Komatsu, Mitsuru Sugawara
    International journal of clinical pharmacology and therapeutics, 59, 12, 787, 793, 2021年09月10日, [国際誌]
    英語, 研究論文(学術雑誌), OBJECTIVE: We previously reported a case where S-1, containing tegafur, gimeracil, and oteracil potassium, induced severe hypertriglyceridemia. After the case, we regularly monitored serum lipid levels and surprisingly observed an additional 4 cases within 1.5 years. We here report the treatment process. CASE REPORT: At least 3 patients exhibited hyperlipidemia at baseline; in 2 of them, this was caused by previous fluoropyrimidine treatment. One patient experienced grade 4 hypertriglyceridemia, and the other 3 grade 3 hypertriglyceridemia. One patient developed temporary serum triglyceride elevation during the S-1 administration period, and the 3 experienced persistent elevation. The severity of serum triglyceride level worsened with increasing administration and peaked in cycles 2 - 6. Fenofibrate 80 - 160 mg/day and S-1 dose reduction were effective, with some significantly and others gradually decreasing to grade 0 - 1. DISCUSSION: The summarized clinical features are as follows: (1) Severe hypertriglyceridemia tends to appear after several treatment cycles and worsens with increasing administration. (2) It tends to occur in patients with hyperlipidemia at baseline. (3) Patients previously affected with fluoropyrimidines-induced hypertriglyceridemia can experience S-1 symptoms. (4) In some cases, it might decrease after the S-1 suspension period. (5) Fibrates and S-1 dose reductions were effective. As the final fluoropyrimidine product is fluorouracil, its presence or that of its metabolizing enzymes and the genetic background of the patients might have affected the results. We should be aware of the risk of temporal and asymptomatic occurrence of S-1-induced hypertriglyceridemia for early detection with appropriate treatment.
  • 悪性黒色腫の肝転移に対して肝切除を行った4症例の報告               
    旭 よう, 神山 俊哉, 柿坂 達彦, 折茂 達也, 長津 明久, 坂本 譲, 蒲池 浩文, 竹内 啓, 三橋 智子, 武冨 紹信
    日本消化器病学会雑誌, 118, 臨増総会, A390, A390, (一財)日本消化器病学会, 2021年03月
    日本語
  • 悪性黒色腫の肝転移に対して肝切除を行った4症例の報告               
    旭 よう, 神山 俊哉, 柿坂 達彦, 折茂 達也, 長津 明久, 坂本 譲, 蒲池 浩文, 竹内 啓, 三橋 智子, 武冨 紹信
    日本消化器病学会雑誌, 118, 臨増総会, A390, A390, (一財)日本消化器病学会, 2021年03月
    日本語
  • Phase II trial of combination treatment with S-1/cetuximab in patients with platinum-ineligible recurrent and/or metastatic squamous cell carcinoma of the head and neck.
    Jun Taguchi, Yasushi Shimizu, Shin Ariga, Tomohiro Goda, Yoshihito Ohhara, Rio Honma, Takuro Noguchi, Satoshi Takeuchi, Ichiro Kinoshita, Toraji Amano, Takatsugu Mizumachi, Satoshi Kano, Miki Takahara, Takahisa Abe, Akihiro Homma, Hirotoshi Dosaka-Akita
    International journal of clinical oncology, 26, 1, 51, 58, 2021年01月, [国内誌]
    英語, 研究論文(学術雑誌), BACKGROUND: The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) in patients who cannot tolerate platinum-based regimens has not been clarified. We aimed to develop a new treatment regimen for patients with R/M SCCHN who are ineligible for platinum-based therapy, by evaluating the effects and safety of tegafur/gimeracil/oteracil (S-1) and cetuximab. METHODS: Platinum-ineligibility was defined as: elderly (aged ≥ 75 years), poor PS, comorbidity, platinum resistance and refusal to undergo platinum-based therapy. Patients received S-1 (80 mg/m2/day for 14 days followed by a seven-day break) and cetuximab (initial dose, 400 mg/m2, followed by 250 mg/m2 weekly) until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). RESULTS: Between September 2014 and September 2018, we enrolled 23 patients. Among the 21 patients who were evaluable, 20 were male [median age, 69 years (range 49-82)]. The ORR was 9 (43%) of 21 patients [95% confidence interval (CI) 22-66]. One and eight patients achieved complete response (CR) and partial response (PR), respectively. The median overall survival (OS) was 13.7 months (95% CI 9.0-18.3) and progression-free survival (PFS) was 5.7 months (95% CI 3.1-8.2). Grade 3/4 adverse events included acneiform rash and skin reactions (33%), hypomagnesemia (19%), hand-foot syndrome (14%), fatigue (14%), mucositis (10%), and anorexia (10%). CONCLUSIONS: Combination treatment with S-1 and cetuximab was effective and tolerated well by patients with platinum-ineligible R/M SCCHN. Registered clinical trial number: UMIN000015123.
  • Prevalence, clinical course, and predictive factors of immune checkpoint inhibitor monotherapy-associated hepatitis in Japan.
    Takashi Kitagataya, Goki Suda, Kazunori Nagashima, Takehiko Katsurada, Koji Yamamoto, Megumi Kimura, Osamu Maehara, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Yoshito Komatsu, Hiroo Hata, Satoshi Takeuchi, Takashige Abe, Jun Sakakibara-Konishi, Takanori Teshima, Akihiro Homma, Naoya Sakamoto
    Journal of gastroenterology and hepatology, 35, 10, 1782, 1788, 2020年10月, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND AND AIM: Immune checkpoint inhibitors (ICI) have revolutionized anti-malignancy therapy and thus have been increasingly used. Although ICI may cause immune-related adverse events (irAE) in various organs, including the liver, the prevalence and predictive factors of irAE have not been clarified. METHODS: In this retrospective study, consecutive patients who had malignancies and were treated with ICI without other chemotherapeutic agents at Hokkaido University Hospital between 2014 and 2019 were screened. Patients were excluded if they were < 20 years old and had insufficient clinical data. RESULTS: Of the 233 patients screened, 202 patients met the inclusion criteria and were included in the analysis. The patients were aged 25-92 years, and 60.9% were male. The patients received nivolumab (n = 137), pembrolizumab (n = 45), ipilimumab (n = 17), atezolizumab (n = 2), and avelumab (n = 1). The prevalence of any grade and grade ≥ 3 irAE hepatitis was 8.4% (17/202) and 4.0% (8/202), respectively. irAE hepatitis occurred at a median duration of 42 days in any grade and 36 days in grade ≥ 3 after ICI initiation. The clinical course of grade ≥ 3 irAE hepatitis was generally favorable; however, 50% required corticosteroid treatment and two patients required additional mycophenolate mofetil. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis. CONCLUSIONS: Grade ≥ 3 irAE hepatitis was observed in 4.0% of the patients who were treated with ICI. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis.
  • Metachronous liver metastases after long-term follow-up of endoscopic resection for rectal neuroendocrine neoplasms: a report of three cases.
    Yuma Hane, Takahiro Tsuchikawa, Kimitaka Tanaka, Yoshitsugu Nakanishi, Toshimichi Asano, Takehiro Noji, Yo Kurashima, Yuma Ebihara, Soichi Murakami, Toru Nakamura, Keisuke Okamura, Satoshi Takeuchi, Toshiaki Shichinohe, Satoshi Hirano
    Surgical case reports, 6, 1, 22, 22, 2020年01月15日, [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: Rectal neuroendocrine neoplasms (NENs) are rare, but their incidence has increased in recent years. The metastasis rate is low in cases of a tumor diameter < 1 cm or depth of invasion lower than the submucosa; therefore, the European Neuroendocrine Tumor Society (ENETS) and the North American Neuroendocrine Tumor Society (NANETS) consensus guidelines recommend endoscopic resection. Since little has been reported on the long-term prognosis of endoscopic resection for rectal NEN, consensus is lacking regarding the follow-up period after endoscopic resection. CASE PRESENTATION: Here, we report three cases of metachronous liver metastasis after long-term follow-up of endoscopic mucosal resection (EMR) for rectal NEN. The pathological findings indicated a depth lower than the submucosa and complete radical resection in all cases and lymphovascular invasion in only one case. All three cases showed metachronous multiple liver metastases after 9-13 years of follow-up for EMR, despite achieving complete resection and without muscular invasion. CONCLUSIONS: Metachronous liver metastases may occur after long interval following endoscopic resection; thus, long-term follow-up is necessary after endoscopic resection for rectal NEN.
  • Late Onset of Non-islet Cell Tumor Hypoglycemia Managed via Multidisciplinary Treatment in a Patient with a Solitary Fibrous Tumor.
    Takeuchi S, Goda T, Taguchi J, Douhata Y, Honma R, Ariga S, Ohhara Y, Shimizu Y, Kinoshita I, Fukuda I, Nagashima Y, Akita H
    Internal medicine (Tokyo, Japan), 57, 16, 2431, 2436, 2018年08月, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌), Solitary fibrous tumor (SFT) is a rare subtype of soft tissue sarcoma (STS). We herein describe a case of late onset of non-islet cell tumor hypoglycemia (NICTH) that was managed via multidisciplinary treatment in a patient with SFT. A 67-year-old man previously diagnosed with SFT 4 years prior to this presentation and treated with several rounds of surgery, presented with massive tumors. Eighteen months following his prescribed chemotherapy, the patient developed hypoglycemia. He was diagnosed with NICTH, after confirming the presence of high molecular weight insulin-like growth factor-2. This case suggests that paraneoplastic syndrome can occur even in cases of rare cancers, such as STS.
  • Early prediction of lenvatinib treatment efficacy by using 18F-FDG PET/CT in patients with unresectable or advanced thyroid carcinoma that is refractory to radioiodine treatment: a protocol for a non-randomized single-arm multicenter observatio
    Takeuchi S, Shiga T, Hirata K, Taguchi J, Magota K, Ariga S, Gouda T, Ohhara Y, Homma R, Shimizu Y, Kinoshita I, Tsuji Y, Homma A, Iijima H, Tamaki N, Dosaka-Akita H
    BMJ open, 8, 8, e021001, 2018年08月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), INTRODUCTION: Lenvatinib, an oral molecular targeted drug, is used to treat patients with unresectable or advanced thyroid carcinoma that is refractory to radioiodine treatment. Effective methods for evaluating molecular targeted drugs are a critical unmet need owing to their expensive costs and unique adverse events. The aim of this study is to determine whether 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT at 1 week after commencing lenvatinib can predict treatment outcomes. DESIGN AND METHODS: This study is planned as a non-randomised single-arm multicentre study; patients with pathologically confirmed differentiated thyroid carcinoma (DTC) with lesions that are refractory to radioiodine treatment are eligible. The main exclusion criteria are medullary or anaplastic carcinoma, prior treatment with chemotherapy, poor general condition and thromboembolism-requiring treatment. Patients to be included in the study will be treated with lenvatinib and undergo FDG-PET/CT examination twice: before and 1 week after the initiation of treatment. Contrast-enhanced CT, the gold standard for evaluation, will be performed at least 4 weeks after the initiation of treatment. The primary objective is to evaluate the ability of the lesion maximum standard uptake value for FDG PET/CT performed 1 week after the initiation of treatment to predict outcomes compared with the response evaluation obtained via contrast-enhanced CT performed at least 4 weeks after the initiation of treatment. ETHICS AND DISSEMINATION: This study is conducted in accordance with the Declaration of Helsinki and has received ethical approval from the institutional review board of the Hokkaido University Hospital (approval number: 015-402). The results of this study will be disseminated through a presentation at a conference and the publication of the data in a peer-reviewed journal. The study will be implemented and reported in line with the SPIRIT statement. TRIAL REGISTRATION NUMBER: UMIN000022592.
  • Therapeutic activity of retroviral replicating vector-mediated prodrug activator gene therapy for pancreatic cancer.
    Inoko K, Hiraoka K, Inagaki A, Takahashi M, Kushibiki T, Hontani K, Takano H, Sato S, Takeuchi S, Nakamura T, Tsuchikawa T, Shichinohe T, Gruber HE, Jolly DJ, Kasahara N, Hirano S
    Cancer gene therapy, 25, 7-8, 184, 195, 2018年08月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Toca 511, a retroviral replicating vector (RRV) encoding the yeast cytosine deaminase (yCD) prodrug activator gene, which mediates conversion of the prodrug 5-fluorocytosine (5-FC) to the anticancer drug 5-fluorouracil (5-FU), is currently being evaluated in Phase II/III clinical trials for glioma, and showing highly promising evidence of therapeutic activity. Here we evaluated RRV-mediated prodrug activator gene therapy as a new therapeutic approach for pancreatic ductal adenocarcinoma (PDAC). RRV spread rapidly and conferred significant cytotoxicity with prodrug in a panel of PDAC cells. Efficient intratumoral replication and complete inhibition of tumor growth upon 5-FC administration were observed in both immunodeficient and immunocompetent subcutaneous PDAC models. Biodistribution of RRV was highly restricted in normal tissues, especially in immunocompetent hosts. Tumor growth inhibition by Toca 511 followed by 5-FC was also confirmed in the orthotopic PDAC model. This study provides the first proof-of-concept for application of Toca 511 and Toca FC (extended release 5-FC) to the treatment of human PDAC, and provided support for inclusion of PDAC in a Phase I study evaluating Toca 511 in various systemic malignancies, (NCT02576665), which has recently been initiated.
  • Pathological complete response of locally advanced colon cancer after preoperative radiotherapy: a case report and narrative review of the literature.
    Sekiya S, Imamura K, Takeuchi S, Teramura K, Watanabe Y, Tamoto E, Takada M, Kinoshita Y, Anbo Y, Nakamura F, Kashimura N, Noguchi H, Miura K, Hirano S
    Surgical case reports, 4, 1, 58, 58, 2018年06月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), BACKGROUND: The oncological effectiveness of preoperative radiotherapy for locally advanced colon cancer is unclear. We report a case of pathological complete response in a patient with locally advanced ascending colon cancer after preoperative radiotherapy following failure of chemotherapy. CASE PRESENTATION: A 65-year-old Japanese woman presented with malaise and hematochezia. A computed tomography (CT) revealed a tumor in the ascending colon which seemed to infiltrate the adjacent structures. She was diagnosed with locally advanced ascending colon cancer stages T4b, N2a, M0, and IIIC. We selected modified FOLFOX6 with panitumumab as neoadjuvant chemotherapy. However, we discontinued the chemotherapy after the 8th cycle because of disease progression and severe adverse effects. The patient then underwent radiotherapy of 60 Gy in 30 fractions, resulting in significant tumor size reduction. One month after the radiotherapy, we performed a right hemicolectomy with multivisceral resection without complications. Histopathologically, we found no residual cancer cells in the resected specimen. The patient remains alive and has not required additional therapies for 24 months, as there are no signs of recurrence. CONCLUSIONS: The present case suggests that preoperative radiotherapy might be an effective treatment options for locally advanced colon cancer.
  • EGFR遺伝子変異とEGFRチロシンキナーゼ阻害薬(EGFR-TKI)に対する反応が異なる肺3重癌の1例               
    合田 智宏, 木下 一郎, 堂畑 雄一, 有賀 伸, 田口 純, 本間 理央, 竹内 啓, 清水 康, 秋田 弘俊, 品川 尚文, 樋田 泰浩, 加賀 基知三
    肺癌, 57, 7, 915, 915, (NPO)日本肺癌学会, 2017年12月, [査読有り]
    日本語
  • Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferation.
    Sato S, Nakamura T, Katagiri T, Tsuchikawa T, Kushibiki T, Hontani K, Takahashi M, Inoko K, Takano H, Abe H, Takeuchi S, Ono M, Kuwabara S, Umemoto K, Suzuki T, Sato O, Nakamura Y, Hirano S
    Oncotarget, 8, 69, 113662, 113672, 2017年12月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), Background: Chromosome 16 open reading frame 74 (C16orf74) is highly expressed in pancreatic ductal adenocarcinoma (PDAC) and is involved in cancer cell proliferation and invasion through binding to calcineurin (CN). Therefore, C16orf74 is a good target for the development of a PDAC treatment. A cell-permeable dominant-negative (DN) peptide that can inhibit the C16orf74/CN interaction was designed to examine whether this peptide can inhibit PDAC cell proliferation in vitro and in vivo. Method: TheDN-C16orf74 peptide, which corresponds to the portion of C16orf74 that interacts with CN, was synthesized, and we assessed its anti-tumor activity in proliferation assays with human PDAC cells and the underlying molecular signaling pathway. Using an orthotopic xenograft model of PDAC, we treated mice intraperitoneally with phosphate-buffered saline (PBS), control peptide, or DN-C16orf74 and analyzed the tumor-suppressive effects. Result: DN-C16orf74 inhibited the binding of C16orf74 to CN in an immunoprecipitation assay. DN-C16orf74 suppressed PDAC cell proliferation, and the level of suppression depended on the expression levels of C16orf74 in vitro. DN-C16orf74 also exhibited anti-tumor effects in orthotopic xenograft model. Furthermore, the tumor-suppressive effect was associated with inhibition of the phosphorylation of Akt and mTOR. Conclusion: The cell-permeable peptide DN-C16orf74 has a strong anti-tumor effect against PDAC in vitro and in vivo.
  • Refining prognosis in patients with hepatocellular carcinoma through incorporation of metabolic imaging biomarkers
    Satoshi Takeuchi, Eric M. Rohren, Reham Abdel-Wahab, Lianchun Xiao, Jeffrey S. Morris, Homer A. Macapinlac, Manal M. Hassan, Ahmed O. Kaseb
    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 44, 6, 969, 978, 2017年06月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Premedication with intravenous magnesium has a protective effect against cisplatin-induced nephrotoxicity
    Yoshitaka Saito, Masaki Kobayashi, Takehiro Yamada, Kumiko Kasashi, Rio Honma, Satoshi Takeuchi, Yasushi Shimizu, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Ken Iseki
    SUPPORTIVE CARE IN CANCER, 25, 2, 481, 487, 2017年02月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Identification of novel serum autoantibodies against EID3 in non-functional pancreatic neuroendocrine tumors
    Koji Hontani, Takahiro Tsuchikawa, Takaki Hiwasa, Toru Nakamura, Takashi Ueno, Toshihiro Kushibiki, Mizuna Takahashi, Kazuho Inoko, Hironobu Takano, Satoshi Takeuchi, Hirotoshi Dosaka-Akita, Masaki Kuwatani, Naoya Sakamoto, Yutaka Hatanaka, Tomoko Mitsuhashi, Hideaki Shimada, Toshiaki Shichinohe, Satoshi Hirano
    Oncotarget, 8, 63, 106206, 106221, Impact Journals LLC, 2017年, [査読有り]
    英語, 研究論文(学術雑誌)
  • Intravenous magnesium premedication has prophylactic efficacy against cisplatin-induced nephrotoxicity without an influence on serum magnesium level.               
    Saito Y, Kobayashi M, Yamada T, Kasashi K, Honma R, Takeuchi S, Shimizu Y, Kinoshita I, Dosaka-Akita H, Iseki K
    Support Care Cancer., 25, 481, 487, 2017年, [査読有り]
  • Role of targeted therapy in metastatic colorectal cancer
    Yoshihito Ohhara, Naoki Fukuda, Satoshi Takeuchi, Rio Honma, Yasushi Shimizu, Ichiro Kinoshita, Hirotoshi Dosaka-Akita
    WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY, 8, 9, 642, 655, 2016年09月, [査読有り]
    英語
  • The key role of calreticulin in immunomodulation induced by chemotherapeutic agents.
    Yamamura Y, Tsuchikawa T, Miyauchi K, Takeuchi S, Wada M, Kuwatani T, Kyogoku N, Kuroda A, Maki T, Shichinohe T, Hirano S
    International journal of clinical oncology, 20, 2, 386, 394, 2015年04月, [査読有り], [国内誌]
    英語, 研究論文(学術雑誌), BACKGROUND: It has recently been shown that certain chemotherapeutic agents can improve host immune responses. The present study aimed to demonstrate the mechanism by which chemotherapeutic agents modify the tumor microenvironment and induce tumor-specific immune responses. METHODS: Three mouse cancer cell lines [CT26 mouse colon cancer cells, B16 melanoma cells and Lewis lung carcinoma (LLC)], 5 human carcinoma cell lines (human esophageal squamous cell carcinoma cell lines TE8 and HEC46 and the human pancreatic carcinoma cell lines PK-9, AsPC-1 and SUIT-2) and 5 chemotherapeutic agents [mitoxantrone (MIT), mitomycin C(MMC), 5-fluorouracil (5FU), camptothecin (CPT-11) and cisplatin (CDDP)] that are frequently used in a clinical setting for cancer treatment were utilized to investigate the surface expression level of calreticulin and HLA class I after exposure to chemotherapeutic agents. RESULTS: Increased calreticulin (CRT) expression on the surface of mouse cell lines and, moreover, increased surface expression levels of both CRT and HLA class I in all human cell lines were observed in cells treated by the chemotherapeutic agents as compared with non-treated cells. The surface expression level of CRT was significantly correlated with the HLA class I expression level in all human cell lines. CONCLUSIONS: In conclusion, chemotherapeutic drugs can improve the immunogenicity of cancer cells in a cell-specific manner through the mechanism of translocation of CRT.
  • Expression of Fucosyltransferase 8 Is Associated with an Unfavorable Clinical Outcome in Non-Small Cell Lung Cancers.
    Honma R, Kinoshita I, Miyoshi E, Tomaru U, Matsuno Y, Shimizu Y, Takeuchi S, Kobayashi Y, Kaga K, Taniguchi N, Dosaka-Akita H
    Oncology, 88, 5, 298, 308, 2015年04月, [査読有り], [国際誌]
    英語, 研究論文(学術雑誌), UNLABELLED: Objecitive: Fucosyltransferase 8 (FUT8), the only enzyme responsible for the core α1,6-fucosylation of asparagine-linked oligosaccharides of glycoproteins, is a vital enzyme in cancer development and progression. We examined FUT8 expression in non-small cell lung cancers (NSCLCs) to analyze its clinical significance. We also examined the expression of guanosine diphosphate-mannose-4,6-dehydratase (GMD), which is imperative for the synthesis of fucosylated oligosaccharides. METHODS: Using immunohistochemistry, we evaluated the expression of FUT8 and GMD in relation to patient survival and prognosis in potentially curatively resected NSCLCs. RESULTS: High expression of FUT8 was found in 67 of 129 NSCLCs (51.9%) and was significantly found in non-squamous cell carcinomas (p = 0.008). High expression of FUT8 was associated with poor survival (p = 0.03) and was also a significant and independent unfavorable prognostic factor in patients with potentially curatively resected NSCLCs (p = 0.047). High expression of GMD was significantly associated with high FUT8 expression (p = 0.04). CONCLUSIONS: High expression of FUT8 is associated with an unfavorable clinical outcome in patients with potentially curatively resected NSCLCs, suggesting that FUT8 can be a prognostic factor. The analysis of FUT8 expression and its core fucosylated products may provide new insights for the therapeutic targets of NSCLCs.
  • Impact of ¹⁸F-FDG PET/CT on the management of adrenocortical carcinoma: analysis of 106 patients.
    Takeuchi S, Balachandran A, Habra MA, Phan AT, Bassett RL Jr, Macapinlac HA, Chuang HH
    European journal of nuclear medicine and molecular imaging, 41, 11, 2066, 2073, 2014年11月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Expression of α1,6-fucosyltransferase is associated with prognosis and histology in non-small cell lung cancers               
    Honma R, Kinoshita I, Miyoshi E, Tomaru U, Matsuno Y, Shimizu Y, Takeuchi S, Kobayashi Y, Kaga K, Taniguchi N, Akita DH
    2014年10月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Impact of initial PET/CT staging in terms of clinical stage, management plan, and prognosis in 592 patients with non-small-cell lung cancer
    Satoshi Takeuchi, Benjapa Khiewvan, Patricia S. Fox, Stephen G. Swisher, Eric M. Rohren, Roland L. Bassett, Homer A. Macapinlac
    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 41, 5, 906, 914, 2014年05月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Utility of F-18-FDG PET/CT in follow-up of patients with low-grade serous carcinoma of the ovary
    Satoshi Takeuchi, Martin Lucchini, Kathleen M. Schmeler, Robert L. Coleman, David M. Gershenson, Mark F. Munsell, Homer A. Macapinlac, Pedro T. Ramirez
    GYNECOLOGIC ONCOLOGY, 133, 1, 100, 104, 2014年04月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Assessment of early changes in 3H-fluorothymidine uptake after treatment with gefitinib in human tumor xenograft in comparison with Ki-67 and phospho-EGFR expression.
    Zhao S, Kuge Y, Zhao Y, Takeuchi S, Hirata K, Takei T, Shiga T, Dosaka-Akita H, Tamaki N
    BMC cancer, 13, 525, 525, Biomed central, 2013年11月06日, [査読有り]
    英語, 研究論文(その他学術会議資料等), Background: The purpose of this study was to evaluate whether early changes in 3'-deoxy-3'-H-3-fluorothymidine (H-3-FLT) uptake can reflect the antiproliferative effect of gefitinib in a human tumor xenograft, in comparison with the histopathological markers, Ki-67 and phosphorylated EGFR (phospho-EGFR). Methods: An EGFR-dependent human tumor xenograft model (A431) was established in female BALB/c athymic mice, which were divided into three groups: one control group and two treatment groups. Mice in the treatment groups were orally administered a partial regression dose (100 mg/kg/day) or the maximum tolerated dose of gefitinib (200 mg/kg/day), once daily for 2 days. Mice in the control group were administered the vehicle (0.1% Tween 80). Tumor size was measured before and 3 days after the start of treatment. Biodistribution of H-3-FLT and F-18-FDG (%ID/g/kg) was examined 3 days after the start of the treatment. Tumor cell proliferative activity with Ki-67 was determined. Immunohistochemical staining of EGFR and measurement of phospho-EGFR were also performed. Results: High expression levels of EGFR and Ki-67 were observed in the A431 tumor. After the treatment with 100 and 200 mg/kg gefitinib, the uptake levels of H-3-FLT in the tumor were significantly reduced to 67% and 61% of the control value, respectively (0.39 +/- 0.09, 0.36 +/- 0.06, 0.59 +/- 0.11% ID/g/kg for 100 mg/kg, 200 mg/kg, and control groups, respectively; p < 0.01 vs. control), but those of F-18-FDG were not. After the treatment with 100 and 200 mg/kg gefitinib, the expression levels of Ki-67 in the tumor were markedly decreased (4.6 +/- 2.4%, 6.2 +/- 1.8%,and 10.4 +/- 5.7% for 100 mg/kg, 200 mg/kg, and control groups, respectively, p < 0.01 vs. control). The expression levels of the phospho-EGFR protein also significantly decreased (29% and 21% of the control value for 100, and 200 mg/kg, respectively p < 0.01 vs. control). There was no statistically significant difference in tumor size between pre- and post-treatments in each group. Conclusion: In our animal model, H-3-FLT uptake levels significantly decreased after the treatment with two different doses of gefitinib before a significant change in tumor size was observed. These results were confirmed by the immunohistochemical staining of Ki-67 and phospho-EGFR protein immunoassay. Thus, it was indicated that early changes in H-3-FLT uptake may reflect the antiproliferative effect of gefitinib in a mouse model of a human epidermoid cancer.
  • 北海道大学病院における上咽頭癌の治療―10年間(2000~2010)のまとめ―
    土屋和彦, 安田耕一, 西川由記子, 木下留美子, 鬼丸力也, 原田慶一, 井上哲也, 加藤徳雄, 清水伸一, 白土博樹, 西岡健, 鈴木恵士郎, 田口大志, 長谷川雅一, 折舘伸彦, 本間明宏, 鈴木清護, 畠山博充, 加納里志, 水町貴諭, 坂下智博, 福田諭, 竹内啓, 田口純
    耳鼻咽喉科展望, 56, 補冊2, 174, 175, 耳鼻咽喉科展望会, 2013年05月05日
    日本語
  • F-18-Fluorothymidine PET/CT as an early predictor of tumor response to treatment with cetuximab in human lung cancer xenografts
    Satoshi Takeuchi, Songji Zhao, Yuji Kuge, Yan Zhao, Ken-Ichi Nishijima, Toshiyuki Hatano, Yasushi Shimizu, Ichiro Kinoshita, Nagara Tamaki, Hirotoshi Dosaka-Akita
    ONCOLOGY REPORTS, 26, 3, 725, 730, 2011年09月, [査読有り]
    英語, 研究論文(学術雑誌)
  • A case of high-grade neuroendocrine carcinoma that improved with bevacizumab plus modified FOLFOX6 as the fourth-line chemotherapy
    Satoshi Takeuchi, Rio Honma, Jun Taguchi, Toraji Amano, Yasushi Shimizu, Ichiro Kinoshita, Kanako Kubota, Yoshihiro Matsuno, Hirotoshi Dosaka-Akita
    Case Reports in Oncology, 4, 2, 260, 266, 2011年05月, [査読有り]
    英語, 研究論文(学術雑誌)
  • 18F‐Fluorothymidine(FLT)による抗EGFR抗体薬の早期治療効果予測               
    竹内啓, 趙松吉, 趙松吉, 久下裕司, 趙莞, 西嶋剣一, 波多野利行, 清水康, 木下一郎, 玉木長良, 秋田弘俊
    日本臨床腫瘍学会学術集会プログラム・抄録集, 9th, 367, 2011年
    英語, 研究論文(その他学術会議資料等)
  • ヒト癌移植マウスにおける抗EGFR抗体(Cetuximab)による分子標的療法:18F‐FMISOを用いた早期治療効果評価               
    趙松吉, 久下裕司, 趙芫, 竹内啓, 村上正紘, 李花, 西嶋剣一, 竹井俊樹, 秋田弘俊, 玉木長良
    核医学, 48, 3, 335, 2011年
    英語, 研究論文(その他学術会議資料等)
  • ヒト癌細胞移植マウスにおける抗EGFR抗体(cetuximab)による分子標的療法:FLTを用いた早期治療効果評価               
    竹内啓, 趙松吉, 久下祐司, 趙莞, 西嶋剣一, 波多野利行, 清水康, 木下一郎, 玉木長良, 秋田弘俊
    日本臨床腫瘍学会学術集会プログラム・抄録集, 8th, 188, 2010年
    英語, 研究論文(その他学術会議資料等)
  • 肉芽腫・腫瘍の鑑別診断におけるdynamic 11C‐MET‐PETの有用性:小動物用PETを用いた基礎的検討               
    趙松吉, 久下裕司, 伊敏, 趙芫, 竹内啓, 波多野利行, 鈴木幸太郎, 孫田惠一, 西嶋剣一, 小華和柾志, 玉木長良
    核医学, 46, 3, S271, 2009年
    英語, 研究論文(その他学術会議資料等)
  • ヒト癌細胞移植マウスにおける抗VEGF抗体(Bevacizumab)による分子標的療法:FLTを用いた早期治療効果評価               
    趙松吉, 久下裕司, 趙芫, 竹内啓, 波多野利行, 西嶋剣一, 木下一郎, 秋田弘毅, 玉木長良
    核医学, 46, 3, S260-S261, 2009年
    英語, 研究論文(その他学術会議資料等)
  • A retrospective study of definitive chemoradiotherapy for elderly patients with esophageal cancer
    Satoshi Takeuchi, Atsushi Htsu, Toshihiko Doi, Takashi Kojima, Keiko Minashi, Kiyomi Mera, Tomonori Yano, Makoto Tahara, Manabu Muto, Keiji Nihei
    AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 30, 6, 607, 611, 2007年12月, [査読有り]
    英語, 研究論文(学術雑誌)
  • Feasibility of oxaliplatin and infusional fluorouracil/leucovorin (FOLFOX4) for Japanese patients with unresectable metastatic colorectal cancer
    Nozomu Fuse, Toshihiko Doi, Atsushi Ohtsu, Satoshi Takeuchi, Takashi Kojima, Keisei Taku, Makoto Tahara, Manabu Muto, Masahiro Asaka, Shigeaki Yoshida
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 37, 6, 434, 439, 2007年06月, [査読有り]
    英語, 研究論文(学術雑誌)
  • New feeding management for percutaneous endoscopic gastrostomy (PEG) using semi-solid food with a new device, the 'CP-PEG connector'
    Santa Hattori, Manabu Muto, Tomonori Yano, Keiko Minashi, Makoto Tahara, Takashi Kojima, Naomi Kiyota, Satoshi Takeuchi, Yasumasa Ezoe, Fumio Ito, Atsushi Ohtsu, Shigeaki Yoshida
    GASTROINTESTINAL ENDOSCOPY, 65, 5, AB170, AB170, 2007年04月, [査読有り]
    英語
  • FOLFOX投与中に間質性肺炎を発症した大腸癌2例の検討               
    藤島 佳未, 小島 隆嗣, 土井 俊彦, 大津 敦, 三梨 桂子, 目良 清美, 竹内 啓, 清田 尚臣, 田原 信
    日本癌治療学会誌, 41, 2, 522, 522, (一社)日本癌治療学会, 2006年09月
    日本語
  • 高齢者食道癌に対する5FU+CDDP+Radiotherapy(FP-RT)による根治的放射線化学療法(CRT)に関する検討               
    竹内 啓, 目良 清美, 矢野 友規, 三梨 桂子, 浜本 康夫, 田原 信, 佐野 寧, 武藤 学, 土井 俊彦, 大津 敦
    日本癌治療学会誌, 40, 2, 653, 653, (一社)日本癌治療学会, 2005年09月
    日本語

その他活動・業績

共同研究・競争的資金等の研究課題

  • 半導体PETと深層学習を利用したFDG PETからの腫瘍血流・代謝の同時定量
    科学研究費助成事業
    2020年04月01日 - 2023年03月31日
    平田 健司, 竹内 啓, 真鍋 治, 久下 裕司
    F-18 fluorodeoxyglucose (FDG)はブドウ糖類似体であり、体内に投与してからポジトロン断層法(PET)で撮影することにより、体内の糖代謝の多寡を画像化できる。原理的には、FDGを投与した直後から連続PET撮影した画像は血流の情報を含む。血流成分を抽出する試みは過去にも行われてきたが、PETの空間分解能の低さによるarterial input function (AIF)取得の困難さ等のため、臨床的に使用されるレベルには至っていない。腫瘍の血流にはdrug deliveryや治療効果判定に関する重要な情報が含まれていると考えられる。そこで本研究では新技術を導入することで、FDGによる腫瘍の糖代謝・血流の同時定量を目指した。今回申請者らが用いる新技術は、ハードウェアとしては高い空間分解能を持つ半導体PETであり、ソフトウェアとしては機械学習の一種であるdeep neural network (DNN)である。高い空間分解能は小さい血管からのAIF取得に役立ち、DNNはコンパートメントモデル・フリーで直接血流を予測するregressorとなりうる。腫瘍血流はO-15標識水のPETによる測定値をgold standardとする。1回のFDG PET撮影で患者負担の増加なしに糖代謝と同時に腫瘍血流が定量することを目指している。2年目である2021年度も新規の前向き臨床試験の立ち上げには到達できなかったが、PETのAI解析に向けて不足するエビデンスを固めるため、O-15標識水やFDGによる後ろ向き研究やファントム実験、画像診断レポートと画像とを組み合わせる研究等を行った。とくにO-15標識水に関しては、PET撮影した肺画像をUCLAの研究者とともに解析し、肺血流の定量値を得ることに成功し、腫瘍血流定量につながる成果が得られた。
    日本学術振興会, 基盤研究(C), 北海道大学, 20K08015
  • 低酸素腫瘍に対する新たな治療戦略の構築
    科学研究費助成事業
    2018年04月01日 - 2021年03月31日
    志賀 哲, 安井 博宣, 竹内 啓, 久下 裕司, 趙 松吉
    「エリブリンが腫瘍の低酸素状態を改善するか?」「化学療法や放射線治療の効果をどの程度改善するか?」「その結果、予後を改善するのか?」の3つの疑問に対し、動物実験および臨床試験を計画した。
    ヒト乳癌細胞を移植した動物実験では、1)エリブリンは腫瘍の低酸素状態を改善し、2)放射線治療後の腫瘍の成長を有意に遅らせ、3)生存率を有意に向上させる事を示す事ができた。また、エリブリンが用量依存的に腫瘍の酸素化を改善し、投与後7日後の酸素化が最大であった事が解った。
    ヒトでの試験は特定臨床試験を予定していたが、POC取得はできなかった。
    日本学術振興会, 基盤研究(B), 18H02757