513 results on '"Nobuaki, Suzuki"'
Search Results
2. High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer
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Kei Furuya, Masao Nakajima, Ryouichi Tsunedomi, Yuki Nakagami, Ming Xu, Hiroto Matsui, Yukio Tokumitsu, Yoshitaro Shindo, Yusaku Watanabe, Shinobu Tomochika, Noriko Maeda, Michihisa Iida, Nobuaki Suzuki, Shigeru Takeda, Shoichi Hazama, Tatsuya Ioka, Yoshinobu Hoshii, Tomio Ueno, and Hiroaki Nagano
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Biomarker ,Bevacizumab ,Chemotherapy ,Metastatic colorectal cancer ,Proteinase-3 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background To improve the prognosis of patients with metastatic colorectal cancer (mCRC), investigating predictive biomarkers of their prognosis and chemotherapeutic responsiveness is necessary. This study aimed to analyze the clinical significance of serum proteinase-3 (PRTN3) as a predictor for prognosis and chemosensitivity, especially to bevacizumab therapy, in mCRC. Methods This single-center retrospective observational study enrolled 79 patients with mCRC in our hospital and 353 patients with colorectal cancer in the TCGA database. Preoperative serum PRTN3 levels were measured using an enzyme-linked immunosorbent assay. The clinicopathological characteristics and prognosis according to serum PRTN3 levels were then evaluated. PRTN3 expression in tumor and stromal cells was evaluated immunohistochemically. The impact of PRTN3 levels on angiogenesis and bevacizumab sensitivity was evaluated using the tube formation assay. Results Serum PRTN3 levels were an independent poor prognostic factor for progression-free survival (PFS) (hazard ratio, 2.082; 95% confidence interval, 1.118-3.647; P=0.010) in patients with mCRC. Similarly, prognostic analysis with TCGA data sets showed poorer overall survival in patients with PRTN3 expression than that in patients without PRTN3 expression, especially in patients with stage IV. Immunohistochemical analysis of resected specimens revealed that stromal neutrophils expressed PRTN3, and their expression level was significantly correlated with serum PRTN3 levels. Interestingly, the effectiveness of first-line chemotherapy was significantly poorer in the high serum PRTN3 level group. High serum PRTN3 was significantly associated with poor PFS (hazard ratio, 3.027; 95% confidence interval, 1.175–7.793; P=0.0161) in patients treated with bevacizumab, an anti-angiogenic inhibitor. The tube formation assay revealed that PRTN3 administration notably augmented angiogenesis while simultaneously attenuating the anti-angiogenic influence exerted by bevacizumab therapy. Conclusions Serum PRTN3 levels could be a novel predictive biomarker of PFS of first-line chemotherapy, especially for bevacizumab therapy, in patients with mCRC
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- 2024
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3. A novel prediction model of pancreatic fistula after pancreaticoduodenectomy using only preoperative markers
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Hiroto Matsui, Yoshitaro Shindo, Daisaku Yamada, Hiroyuki Ogihara, Yukio Tokumitsu, Masao Nakajima, Michihisa Iida, Nobuaki Suzuki, Shigeru Takeda, Yuki Nakagami, Shogo Kobayashi, Hidetoshi Eguchi, Tatsuya Ioka, Yoshihiko Hamamoto, and Hiroaki Nagano
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Postoperative pancreatic fistula ,Pancreaticoduodenectomy ,Discrete Bayes classifier ,Prediction model ,Surgery ,RD1-811 - Abstract
Abstract Background Since clinically relevant postoperative pancreatic fistula (CR-POPF) can cause intra-abdominal hemorrhage and abscesses, leading to surgery-related deaths after pancreaticoduodenectomy (PD), its preoperative prediction is important to develop strategies for surgical procedures and perioperative management. This study aimed to establish a novel prediction model for CR-POPF using preoperative markers. Methods On a training set of 180 patients who underwent PD at the Yamaguchi University Hospital, a combination of CR-POPF predictors were explored using the leave-one-out method with a unique discrete Bayes classifier. This predictive model was confirmed using a validation set of 366 patients who underwent PD at the Osaka University Hospital. Results In the training set, CR-POPF occurred in 60 (33%) of 180 patients and 130 (36%) of 366 patients in the validation set using selected markers. In patients with pancreatic ductal adenocarcinoma (PDAC), the main pancreatic duct (MPD) index showed the highest prognostic performance and could differentiate CR-POPF with 87% sensitivity and 81% specificity among 84 patients in the training set. In the validation set, the sensitivity and specificity of the MPD index-based model for 130 PDAC samples were 93% and 87%, respectively. In patients with non-PDAC, the MPD index/body mass index (BMI) combination showed the highest prognostic performance and could differentiate CR-POPF with 84% sensitivity and 57% specificity among 96 patients in the training set. In the validation set, the sensitivity and specificity of the MPD index/BMI-based model for 236 non-PDAC samples were 85% and 53%, respectively. Conclusion We developed a novel prediction model for pancreatic fistulas after PD using only preoperative markers. The MPD index and MPD index/BMI combination will be useful for CR-POPF assessment in PDAC and non-PDAC samples, respectively.
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- 2023
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4. Impact of Medina classification on clinical outcomes of imaging-guided coronary bifurcation stenting
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Yoshinobu Murasato, Yoshihisa Kinoshita, Masahiro Yamawaki, Takayuki Okamura, Ryoji Nagoshi, Yusuke Watanabe, Nobuaki Suzuki, Takahiro Mori, Toshiro Shinke, Junya Shite, and Ken Kozuma
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Coronary bifurcation ,Drug-eluting stent ,Intracoronary imaging ,Medina classification ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: Intracoronary imaging improves clinical outcomes after stenting of complex coronary bifurcation lesions (CBLs), but the impact of Medina classification-based CBL distribution on outcomes of imaging-guided bifurcation stenting is unclear. Methods: In this integrated analysis of four previous studies, in which all CBLs were treated with drug-eluting stents under intravascular ultrasound or optical coherence tomography guidance, the distribution of 763 CBLs was assessed using angiographic Medina classification. Major adverse cardiac events (MACE), including target lesion revascularization (TLR), myocardial infarction, stent thrombosis, and cardiac death, were investigated at 1-year follow-up. Results: The most and least prevalent Medina subtypes were 0-1-0 (27.9 %) and 0-0-1 lesions (2.8 %). The most and least frequent MACE/TLR rates were 18.2 %/18.2 % for 0-0-1 lesions and 4.1 %/2.8 % for 0-1-0 lesions. Risks were higher for 0-0-1 lesions than for 0-1-0 lesions for both MACE (hazard ratio [HR]: 4.04, 95 % confidence interval [CI]: 1.21–13.45, p = 0.02) and TLR (HR: 6.19, 95 % CI: 1.69–22.74, p = 0.006). MACE rates were similar for true and non-true CBLs excluding 0-0-1 lesions (8.2 % and 5.9 %, HR 1.54, 95 % CI: 0.86–2.77, p = 0.15), while MACE (HR: 3.25, 95 % CI: 1.10–9.63, p = 0.03) and TLR (HR: 4.24, 95 % CI: 1.38–12.96, p = 0.01) risks were higher for 0-0-1 lesions. Conclusions: This integrated analysis of imaging-guided bifurcation stenting demonstrated similar clinical outcomes in true and non-true CBLs, except for 0-0-1 lesions, which had a significantly higher risk of MACE/TLR.
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- 2023
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5. Impact of coronary bifurcation angle on stent malapposition in a randomized comparison between proximal optimization technique followed by side branch dilatation and kissing balloon inflation
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Masahiro Yamawaki, Yoshinobu Murasato, Yusuke Watanabe, Yoshihisa Kinoshita, Munenori Okubo, Kazuhiko Yumoto, Naoki Masuda, Hiromasa Otake, Jiro Aoki, Gaku Nakazawa, Yohei Numasawa, Tatsuya Ito, Junya Shite, Takayuki Okamura, Kensuke Takagi, Kayoko Kozuma, Thierry Lefèvre, Bernard Chevalier, Yves Louvard, Nobuaki Suzuki, and Ken Kozuma
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Percutaneous coronary intervention ,Coronary bifurcation ,Optical coherence tomography ,Drug-eluting stent ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: The impact of coronary bifurcation angle (BA) on incomplete stent apposition (ISA) after crossover stenting followed by side branch (SB) intervention has not been established. Methods: A total of 100 crossover stentings randomly treated with proximal optimization technique followed by short balloon dilation in the SB (POT-SBD group, 48 patients) and final kissing balloon technique (KBT group, 52 patients) were analyzed in the PROPOT trial. Major ISA with maximum distance > 400 μm and its location was determined using optical coherence tomography before SB intervention and at the final procedure. The BA was defined as the angle between the distal main vessel and SB. Optimal POT was determined when the difference in stent volume index between the proximal and distal bifurcation was greater than the median value (0.86 mm3/mm) before SB intervention. Result: Major ISA was more frequently observed in the POT-SBD than in the KBT group (35% versus 17%, p
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- 2023
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6. Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity
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Kou Kanesada, Ryouichi Tsunedomi, Shoichi Hazama, Hiroyuki Ogihara, Yoshihiko Hamamoto, Yoshitaro Shindo, Hiroto Matsui, Yukio Tokumitsu, Shin Yoshida, Michihisa Iida, Nobuaki Suzuki, Shigeru Takeda, Tatsuya Ioka, and Hiroaki Nagano
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colorectal cancer ,irinotecan ,neutropenia ,pancreatic cancer ,R3HCC1 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Objective Irinotecan is a useful anticancer drug for colorectal cancer treatment. UGT1A1*28 and *6 gene polymorphisms are known risk factors for irinotecan‐associated toxicity. However, severe adverse effects due to irinotecan have been observed even in patients who do not harbor UGT1A1*28 or *6. We investigated gene polymorphisms in the whole exome to identify useful biomarkers for irinotecan toxicity other than UGT1A. Methods A total of 178 patients with metastatic colorectal cancer (mCRC) and 87 patients with pancreatic cancer were treated with FOLFIRI, FOLFOX, FOLFOXIRI, modified FOLFIRINOX, or gemcitabine plus nab‐paclitaxel. Genome‐wide screening was performed using whole‐exome sequencing (WES), and validation analysis was performed using qPCR with a hydrolysis probe. Results Using WES after a doublet chemotherapy regimen comprising irinotecan and 5‐fluorouracil (n = 15), seven single nucleotide polymorphisms (SNPs) were identified as candidate biomarkers for irinotecan‐associated toxicity of neutropenia. Among the seven SNPs, an SNP in R3H domain and coiled‐coil containing 1 (R3HCC1; c.919G > A, rs2272761) showed a significant association with neutropenia (>grade 3) after doublet chemotherapy. Patients receiving irinotecan including triplet chemotherapy, FOLFOXIRI for mCRC (n = 23) or modified FOLFIRINOX for pancreatic cancer (n = 40), also showed significant linear trends between R3HCC1 polymorphism and neutropenia (p = 0.017 and 0.046, respectively). No significant association was observed in patients treated with irinotecan‐free regimens, FOLFOX for mCRC (n = 66), and gemcitabine plus nab‐paclitaxel for pancreatic cancer (n = 47). Conclusion Thus, an SNP in the R3HCC1 gene may be a useful biomarker for the toxicity of irinotecan‐containing chemotherapy for mCRC and pancreatic cancer.
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- 2023
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7. The usefulness of tranexamic acid for bleeding symptoms of chronic consumptive coagulopathy complicated by aortic disease: a single-institute, retrospective study of 14 patients
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Naruko Suzuki, Nobuaki Suzuki, Yuka Kawaguchi, Shuichi Okamoto, Takeshi Kanematsu, Akira Katsumi, Atsuo Suzuki, Shogo Tamura, Tetsuhito Kojima, Hitoshi Kiyoi, and Tadashi Matsushita
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Disseminated intravascular coagulation ,Tranexamic acid ,Aortic aneurysm ,Aneurysm ,Dissecting ,Endovascular procedures ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract Background Tranexamic acid (TXA) is an antifibrinolytic drug that blocks lysine-binding sites on the profibrinolytic enzyme plasminogen. Aortic diseases with chronic consumption coagulopathy may lead to disseminated intravascular coagulation (DIC) and cause fatal bleeding. Although the use of antifibrinolytic agents in DIC is generally not recommended due to enhanced fibrin deposition risking thrombotic symptoms, the efficacy of TXA has been reported in several cases of DIC with aortic diseases. However, the efficacy and safety of TXA for bleeding symptoms of chronic consumption coagulopathy with aortic diseases have not been studied in detail. Methods We evaluated the efficacy of TXA in 14 patients with chronic consumptive coagulopathy due to aortic disease complicated by bleeding symptoms. Changes in coagulation and fibrinolysis parameters from baseline were analyzed with Wilcoxon matched-pairs signed-rank tests, excluding missing values. Kaplan-Meier curves were used to analyze overall survival. Results Median age was 78.5 years (range, 66–89 years) and median observation period was 448 days (range, 0–2282 days). Twelve patients had chronic renal failure and 1 patient had chronic liver failure. Before starting treatment, median Japanese Ministry of Health and Welfare DIC diagnostic criteria score was 8 (range, 4–11) and median platelet count was 64 × 109/L (range, 25–97 × 109/L). Twelve patients underwent evaluation of bleeding symptoms after introduction of TXA, and 10 of those 12 patients showed improved bleeding tendencies within 30 days (median, 5.0 days). One patient with chronic liver failure showed worsening of bleeding symptoms. Although only one patient was initiated TXA in combination with anticoagulants, no significant worsening of thrombotic events was observed within 30 days. Conclusions TXA therapy appears effective against chronic consumptive coagulopathy with bleeding due to aortic disease, with few side effects.
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- 2023
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8. The seroprevalence of neutralizing antibodies against the adeno-associated virus capsids in Japanese hemophiliacs
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Yuji Kashiwakura, Nemekhbayar Baatartsogt, Shoji Yamazaki, Azusa Nagao, Kagehiro Amano, Nobuaki Suzuki, Tadashi Matsushita, Akihiro Sawada, Satoshi Higasa, Naoya Yamasaki, Teruhisa Fujii, Taemi Ogura, Hideyuki Takedani, Masashi Taki, Takeshi Matsumoto, Jun Yamanouchi, Michio Sakai, Masako Nishikawa, Yutaka Yatomi, Koji Yada, Keiji Nogami, Ryota Watano, Takafumi Hiramoto, Morisada Hayakawa, Nobuhiko Kamoshita, Akihiro Kume, Hiroaki Mizukami, Shizukiyo Ishikawa, Yoichi Sakata, and Tsukasa Ohmori
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antibodies ,neutralizing ,dependovirus ,treatment outcome ,genetic therapy ,virus vector ,Genetics ,QH426-470 ,Cytology ,QH573-671 - Abstract
Adeno-associated virus (AAV) vectors are promising modalities of gene therapy to address unmet medical needs. However, anti-AAV neutralizing antibodies (NAbs) hamper the vector-mediated therapeutic effect. Therefore, NAb prevalence in the target population is vital in designing clinical trials with AAV vectors. Hence, updating the seroprevalence of anti-AAV NAbs, herein we analyzed sera from 100 healthy individuals and 216 hemophiliacs in Japan. In both groups, the overall seroprevalence against various AAV serotypes was 20%–30%, and the ratio of the NAb-positive population increased with age. The seroprevalence did not differ between healthy participants and hemophiliacs and was not biased by the concomitant blood-borne viral infections. The high neutralizing activity, which strongly inhibits the transduction with all serotypes in vitro, was mostly found in people in their 60s or of older age. The multivariate analysis suggested that “60s or older age” was the only independent factor related to the high titer of NAbs. Conversely, a large proportion of younger hemophiliacs was seronegative, rendering them eligible for AAV-mediated gene therapy in Japan. Compared with our previous study, the peak of seroprevalences has shifted to older populations, indicating that natural AAV exposure in the elderly occurred in their youth but not during the last decade.
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- 2022
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9. Risk factors for non‐gastric‐cancer‐related death after gastrectomy in elderly patients
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Michihisa Iida, Shigeru Takeda, Chiyo Nakashima, Mitsuo Nishiyama, Yusaku Watanabe, Nobuaki Suzuki, Shigefumi Yoshino, Yuki Nakagami, Tsuyoshi Tanabe, and Hiroaki Nagano
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elderly ,gastrectomy ,gastric cancer ,prognosis ,risk factors ,Surgery ,RD1-811 ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Aim To identify preoperative factors, especially other diseases that cause death, that are associated with the prognosis of gastrectomy in elderly patients with gastric cancer. Methods This retrospective study included a total of 211 consecutive patients aged ≥75 years who underwent radical gastrectomy due to gastric cancer. Time‐dependent receiver operating characteristic curve analysis was performed to determine the optimal cutoff values for various perioperative factors. Risk factors for the overall survival and death from other diseases were analyzed using the Cox proportional hazards model. Results Among the all perioperative factors, sex, neutrophil‐to‐lymphocyte ratio, skeletal muscle mass index, and lymph node dissection in accordance with guidelines or not extracted as independent risk factors for death from other diseases. In an analysis restricted to the preoperative factors, sex, neutrophil‐to‐lymphocyte ratio, and skeletal muscle mass index of the patients were extracted as independent risk factors for death from other diseases and overall survival. We divided the patients into four groups according to the number of preoperative risk factors for death from other diseases and found that the 5‐year non‐gastric‐cancer‐related survival was different among the four groups (risk factor 0, 91.7%; risk factor 1, 83.3%; risk factor 2, 56.3%; risk factor 3, 27.2%; P
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- 2022
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10. CD4 and FOXP3 as predictive markers for the recurrence of T3/T4a stage II colorectal cancer: applying a novel discrete Bayes decision rule
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Yuki Nakagami, Shoichi Hazama, Nobuaki Suzuki, Shin Yoshida, Shinobu Tomochika, Hiroto Matsui, Yoshitaro Shindo, Yukio Tokumitsu, Satoshi Matsukuma, Yusaku Watanabe, Michihisa Iida, Ryouichi Tsunedomi, Shigeru Takeda, Tomonobu Fujita, Yutaka Kawakami, Hiroyuki Ogihara, Yoshihiko Hamamoto, Tatsuya Ioka, Tsuyoshi Tanabe, Tomio Ueno, and Hiroaki Nagano
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Colorectal cancer ,Discrete Bayes decision rule ,Prognosis ,CD4 ,Forkhead box P3 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background We recently reported the relapse-free survival (RFS) significance of the combination of CD4+ and forkhead box P3+ (FOXP3) T-cell densities identified by immunohistochemistry in patients with stage I, II, and III colorectal cancer (CRC) who underwent curative resections. This study was designed to determine the optimal combination of markers that predict recurrence in patients with T factors of T3/T4a stage II CRC by applying a novel Bayes decision rule. Methods Using 137 cancer tissue specimens from T3/T4a stage II patients, 12 clinicopathologic and immune factors were analysed as predictive candidates for recurrence. Results Our study showed that the combination of low CD4+ and low FOXP3+ T-cell densities resulted in extremely poor RFS. Conclusions Adjuvant chemotherapy may be considered for patients with a combination of low CD4+ and low FOXP3+ T-cell densities. The discovery of this new prognostic indicator is important for the appropriate management of patients undergoing curative resection for T3/T4a stage II CRC.
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- 2022
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11. Elevated expression of RAB3B plays important roles in chemoresistance and metastatic potential of hepatoma cells
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Ryouichi Tsunedomi, Kiyoshi Yoshimura, Yuta Kimura, Mitsuo Nishiyama, Nobuyuki Fujiwara, Satoshi Matsukuma, Shinsuke Kanekiyo, Hiroto Matsui, Yoshitaro Shindo, Yusaku Watanabe, Yukio Tokumitsu, Shin Yoshida, Michihisa Iida, Nobuaki Suzuki, Shigeru Takeda, Tatsuya Ioka, Shoichi Hazama, and Hiroaki Nagano
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Cancer stem cell ,Hepatoma ,RAB3B ,Exosome ,Sphere ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Cancer stem cells (CSCs) are thought to play important roles in carcinogenesis, recurrence, metastasis, and therapy-resistance. We have successfully induced cancer stem-like sphere cells (CSLCs) which possess enhanced chemoresistance and metastatic potential. To enable the development of targeted therapy against CSLCs, we identified a gene responsible for this phenotype in CSLC. Methods Human hepatoma cell line SK-HEP-1 was used for CSLC induction with a unique sphere inducing medium, and HuH-7 cells were used as non-sphere forming cells in the same condition. RNA-sequencing was performed followed by validation with quantitative RT-PCR and western blotting. Knockdown experiments were done by using CRISPR-Cas9 genome-editing, and the rescue experiments were performed using the expressing plasmid vector. Chemoresistance and liver metastasis of the cells, was studied following the splenic injection of cells to severely immune deficient mice and evaluated using the MTS assay. Quantification of exosomes in the medium was done using ELISA. Results RAB3B was identified as an up-regulated gene in both CSLCs and prognostically poor hepatocellular carcinoma (HCC) by RNA-sequencing. RAB3B-KD cells showed altered CSLC phenotypes such as sphere formation, chemoresistance, and metastatic potentials, and those were rescued by RAB3B complementation. Increased exosome secretion was observed in CSLCs, and it was not observed in the RAB3B-KD cells. In addition, the RAB3B expression correlated with the expression of ABCG2, APOE, LEPR, LXN, and TSPAN13. Conclusion The up regulation of RAB3B may play an important role in the chemoresistance and metastatic potential of CSLCs.
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- 2022
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12. Development and validation of a novel qualitative test for plasma fibrinogen utilizing clot waveform analysis
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Atsuo Suzuki, Nobuaki Suzuki, Takeshi Kanematsu, Sho Shinohara, Hiroshi Kurono, Nobuo Arai, Shuichi Okamoto, Naruko Suzuki, Shogo Tamura, Ryosuke Kikuchi, Akira Katsumi, Tetsuhito Kojima, and Tadashi Matsushita
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Medicine ,Science - Abstract
Abstract Plasma fibrinogen is commonly examined by Clauss fibrinogen assay, which cannot distinguish between quantitative and qualitative fibrinogen anomalies. However, our previously reported Clauss fibrinogen assay utilizing clot waveform analysis (Clauss-CWA) provides additional information that contributes to the classification of fibrinogen anomalies. In this study, we adopted the Clauss-CWA method for an autoanalyzer to automatically measure the antigenic estimate (eAg) of fibrinogen in addition to the functional amount (Ac), and to thus provide the Ac/eAg ratio as a qualitative indicator. Performance was validated by receiver operating characteristics (ROC) and precision recall (PR) curve analyses using a patient cohort, consisting of a training cohort (n = 519) and a validation cohort (n = 523), both of which contained cases of congenital (hypo)dysfibrinogenemia as qualitative defects. We obtained an optimal cutoff of 0.65 for Ac/eAg by ROC curve analysis of the training cohort, offering superior sensitivity (> 0.9661) and specificity (1.000). This cutoff was validated in the validation cohort, providing positive predictive value > 0.933 and negative predictive value > 0.998. PR curve analysis also showed that Clauss-CWA provided excellent performance for detecting qualitative fibrinogen anomalies. The Clauss-CWA method may represent a useful approach for detecting qualitative fibrinogen abnormalities in routine laboratory testing.
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- 2022
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13. A Deep Learning-Based Model for Classifying Osteoporotic Lumbar Vertebral Fractures on Radiographs: A Retrospective Model Development and Validation Study
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Yohei Ono, Nobuaki Suzuki, Ryosuke Sakano, Yasuka Kikuchi, Tasuku Kimura, Kenneth Sutherland, and Tamotsu Kamishima
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osteoporotic vertebral fractures ,radiography ,deep learning ,convolutional neural networks ,computer-aided diagnosis ,automatic classification ,Photography ,TR1-1050 ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Electronic computers. Computer science ,QA75.5-76.95 - Abstract
Early diagnosis and initiation of treatment for fresh osteoporotic lumbar vertebral fractures (OLVF) are crucial. Magnetic resonance imaging (MRI) is generally performed to differentiate between fresh and old OLVF. However, MRIs can be intolerable for patients with severe back pain. Furthermore, it is difficult to perform in an emergency. MRI should therefore only be performed in appropriately selected patients with a high suspicion of fresh fractures. As radiography is the first-choice imaging examination for the diagnosis of OLVF, improving screening accuracy with radiographs will optimize the decision of whether an MRI is necessary. This study aimed to develop a method to automatically classify lumbar vertebrae (LV) conditions such as normal, old, or fresh OLVF using deep learning methods with radiography. A total of 3481 LV images for training, validation, and testing and 662 LV images for external validation were collected. Visual evaluation by two radiologists determined the ground truth of LV diagnoses. Three convolutional neural networks were ensembled. The accuracy, sensitivity, and specificity were 0.89, 0.83, and 0.92 in the test and 0.84, 0.76, and 0.89 in the external validation, respectively. The results suggest that the proposed method can contribute to the accurate automatic classification of LV conditions on radiography.
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- 2023
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14. Successful ligation of posterior tibial vein aneurysm performed according to intraoperative venography results
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Masaaki Naganuma, MD, PhD, Yasushi Kudo, MD, Nobuaki Suzuki, MD, PhD, Shinya Masuda, MD, PhD, and Koichi Nagaya, MD, PhD
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Aneurysm ,Deep vein thrombosis ,Pulmonary embolism ,Veins ,Venography ,Surgery ,RD1-811 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
A 23-year-old woman was diagnosed with a posterior tibial vein aneurysm that had resulted in deep vein thrombosis and a pulmonary embolism. The patient responded well to anticoagulation therapy, and surgical resection was planned to prevent recurrence. She was scheduled to undergo tangential aneurysmectomy and lateral venorrhaphy. However, the aneurysm could not be completely exposed because of adhesions. Therefore, venography was performed to identify the inflow and outflow vessels, which were ligated because an accessory venous communication was identified. Intraoperative venography can aid in the selection of simple ligation or reconstruction of a venous communication for the treatment of posterior tibial vein aneurysms.
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- 2021
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15. Structure–function studies of ultrahigh molecular weight isoprenes provide key insights into their biosynthesis
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Hiroyuki Kajiura, Takuya Yoshizawa, Yuji Tokumoto, Nobuaki Suzuki, Shinya Takeno, Kanokwan Jumtee Takeno, Takuya Yamashita, Shun-ichi Tanaka, Yoshinobu Kaneko, Kazuhito Fujiyama, Hiroyoshi Matsumura, and Yoshihisa Nakazawa
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Biology (General) ,QH301-705.5 - Abstract
Kajiura and Yoshizawa et al. identify three new prenyltransferases in the tree Eucommia ulmoides that synthesize exceptionally high molecular weight trans-1,4-polyisoprene (TPI). Through crystal structure and mutational analyses, they identify key residues required for TPI synthesis and reveal its functional importance in seed development.
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- 2021
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16. Efficacy of intraoperative recurrent laryngeal neuromonitoring during surgery for esophageal cancer
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Shigeru Takeda, Michihisa Iida, Shinsuke Kanekiyo, Mitsuo Nishiyama, Yukio Tokumitsu, Yoshitaro Shindo, Shin Yoshida, Nobuaki Suzuki, Shigefumi Yoshino, and Hiroaki Nagano
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esophageal cancer ,esophagectomy ,intraoperative neurophysiological monitoring ,minimally invasive surgery ,recurrent laryngeal nerve palsy ,Surgery ,RD1-811 ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Aim To evaluate the efficacy of intraoperative neuromonitoring in identifying recurrent laryngeal nerves and decreasing the incidence of nerve injury in minimally invasive esophagectomies for esophageal cancers. Methods A total of 167 minimally invasive esophagectomy patients were retrospectively reviewed. They were divided into intraoperative neuromonitoring (n = 84) and no intraoperative neuromonitoring (n = 83) groups, based on whether or not intraoperative neuromonitoring was used during surgery. We compared short‐term surgical outcomes and incidence of recurrent laryngeal nerve palsy between the two groups before and after propensity score matching. The association between the loss of signal and recurrent laryngeal nerve palsy was also evaluated. Results The incidence of recurrent laryngeal nerve palsy (grade 2 and higher) was lower in the intraoperative neuromonitoring group than in the no intraoperative neuromonitoring group (6.0% vs 21.2%, P = 0.02). The rate of recurrent laryngeal nerve palsy recovery within 6 months was also significantly higher in the intraoperative neuromonitoring group (87.5% vs 20.0%, P
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- 2021
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17. Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer
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Bernhard Mlecnik, Alessandro Lugli, Gabriela Bindea, Florence Marliot, Carlo Bifulco, Jiun-Kae Jack Lee, Inti Zlobec, Tilman T. Rau, Martin D. Berger, Iris D. Nagtegaal, Elisa Vink-Börger, Arndt Hartmann, Carol I. Geppert, Julie Kolwelter, Susanne Merkel, Robert Grützmann, Marc Van den Eynde, Anne Jouret-Mourin, Alex Kartheuser, Daniel Léonard, Christophe Remue, Julia Wang, Prashant Bavi, Michael H. A. Roehrl, Pamela S. Ohashi, Linh T. Nguyen, SeongJun Han, Heather L. MacGregor, Sara Hafezi-Bakhtiari, Bradly G. Wouters, Giuseppe V. Masucci, Emilia K. Andersson, Eva Zavadova, Michal Vocka, Jan Spacek, Lubos Petruzelka, Bohuslav Konopasek, Pavel Dundr, Helena Skalova, Kristyna Nemejcova, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Gennaro Ciliberto, Michele Maio, Luigi Laghi, Fabio Grizzi, Tessa Fredriksen, Bénédicte Buttard, Lucie Lafontaine, Pauline Maby, Amine Majdi, Assia Hijazi, Carine El Sissy, Amos Kirilovsky, Anne Berger, Christine Lagorce, Christopher Paustian, Carmen Ballesteros-Merino, Jeroen Dijkstra, Carlijn van de Water, Shannon van Lent-van Vliet, Nikki Knijn, Ana-Maria Mușină, Dragos-Viorel Scripcariu, Boryana Popivanova, Mingli Xu, Tomonobu Fujita, Shoichi Hazama, Nobuaki Suzuki, Hiroaki Nagano, Kiyotaka Okuno, Toshihiko Torigoe, Noriyuki Sato, Tomohisa Furuhata, Ichiro Takemasa, Prabhu Patel, Hemangini H. Vora, Birva Shah, Jayendrakumar B. Patel, Kruti N. Rajvik, Shashank J. Pandya, Shilin N. Shukla, Yili Wang, Guanjun Zhang, Yutaka Kawakami, Francesco M. Marincola, Paolo A. Ascierto, Bernard A. Fox, Franck Pagès, and Jérôme Galon
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Immunoscore ,colon cancer ,prognosis ,predictive biomarkers ,early-stage ,tumor microenvironment ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival (OS), prognosis in Stage I, Stage II, Stage II-high-risk, and microsatellite-stable (MSS) patients. RESULTS: High-Immunoscore presented with the lowest risk of recurrence in both cohorts. In Stage I/II, recurrence-free rates at 5 years were 78.4% (95%-CI, 74.4–82.6), 88.1% (95%-CI, 85.7–90.4), 93.4% (95%-CI, 91.1–95.8) in low, intermediate and high Immunoscore, respectively (HR (Hi vs. Lo) = 0.27 (95%-CI, 0.18–0.41); p < 0.0001). In Cox multivariable analysis, the association of Immunoscore to outcome was independent (TTR: HR (Hi vs. Lo) = 0.29, (95%-CI, 0.17–0.50); p < 0.0001) of the patient’s gender, T-stage, sidedness, and microsatellite instability-status (MSI). A significant association of Immunoscore with survival was found for Stage II, high-risk Stage II, T4N0 and MSS patients. The Immunoscore also showed significant association with TTR in Stage-I (HR (Hi vs. Lo) = 0.07 (95%-CI, 0.01–0.61); P = 0.016). The Immunoscore had the strongest (69.5%) contribution χ2 for influencing survival. Patients with a high Immunoscore had prolonged TTR in T4N0 tumors even for patients not receiving chemotherapy, and the Immunoscore remained the only significant parameter in multivariable analysis. CONCLUSION: In early CC, low Immunoscore reliably identifies patients at risk of relapse for whom a more intensive surveillance program or adjuvant treatment should be considered.
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- 2023
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18. Viral elimination is essential for improving surgical outcomes of hepatitis C virus‐related hepatocellular carcinoma: Multicenter retrospective analysis
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Masao Nakajima, Shogo Kobayashi, Hiroshi Wada, Akira Tomokuni, Hidenori Takahashi, Takehiro Noda, Hiroto Matsui, Satoshi Matsukuma, Shinsuke Kanekiyo, Yoshitaro Shindo, Yukio Tokumitsu, Yuki Nakagami, Nobuaki Suzuki, Shigeru Takeda, Masahiro Tanabe, Katsuyoshi Ito, Yoshinobu Hoshii, Hidetoshi Eguchi, and Hiroaki Nagano
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hepatectomy ,hepatitis C virus ,hepatocellular carcinoma ,regression of liver fibrosis ,sustained virologic response ,Surgery ,RD1-811 ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Aim The impact of sustained virologic response (SVR) on surgical outcomes for patients with hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the influence of SVR on long‐term surgical outcomes after hepatectomy. Methods This multicenter study included 504 patients who underwent curative resection for HCV‐related HCC. Patients with a history of HCC treatment, HBV infection, poor liver function, and tumor with major vascular invasion were excluded. Long‐term surgical outcomes (overall survival [OS] and recurrence‐free survival [RFS]) among patients who achieved SVR before hepatectomy (Pre‐SVR group: 58 patients), after hepatectomy (Post‐SVR group: 54 patients), and without SVR (Non‐SVR group: 186 patients) were compared after adjusting for 13 confounding factors. Using the surgically resected specimens, comparison of the pathological changes in liver fibrosis between the first and second hepatectomy were analyzed. Results Patients with SVR were younger, had better liver function, and less liver fibrosis compared to patients without SVR. Propensity score‐matched OS and RFS were significantly better in Pre‐SVR group than Non‐SVR group (P = .029 and P = .009, respectively). Inverse probability‐weighted OS and RFS were also significantly better in the Post‐SVR group (P = .001 and P = .021, respectively) than in the Non‐SVR group. Histopathological evaluation revealed that only the patients with SVR had regression of liver fibrosis (P
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- 2020
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19. AKATSUKI study: a prospective, multicentre, phase IV study evaluating the safety of emicizumab under and immediately after immune tolerance induction therapy in persons with congenital haemophilia A with factor VIII inhibitors
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Nobuaki Suzuki, Tadashi Matsushita, Keiji Nogami, Azusa Nagao, Chiai Nagae, Haruko Yamaguchi-Suita, Yui Kyogoku, and Akiko Ioka
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Medicine - Published
- 2022
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20. The influence of hepatitis C virus eradication on hepatocarcinogenesis in patients with hemophilia
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Yosuke Inukai, Norihiro Imai, Kenta Yamamoto, Takanori Ito, Yoji Ishizu, Takashi Honda, Shuichi Okamoto, Takeshi Kanematsu, Nobuaki Suzuki, Tadashi Matsushita, Masatoshi Ishigami, and Mitsuhiro Fujishiro
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Hepatitis C ,Hepatocellular carcinoma ,Sustained virological response ,Hemophilia ,Carcinogenesis ,Specialties of internal medicine ,RC581-951 - Abstract
Introduction and objectives: Hepatitis C virus (HCV) infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. Although recent progress in direct-acting-antivirals has facilitated a high rate of sustained virological response (SVR), the clinical influence of HCV eradication in hemophilia patients remains unclear. This study aimed to compare the clinical outcomes of SVR against HCV in patients with and without hemophilia. Patients and methods: The study enrolled 699 patients who achieved SVR after HCV antiviral treatment. Patients were divided into two groups: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). We evaluated patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR. Results: Compared with the NH group, patients in the H-group were significantly younger and had a lower hepatic fibrosis score. No difference was found in the incidence of liver-related disease or overall death between the two groups over a mean follow-up period of 7 years.Four patients in the H group and 36 patients in the NH group were diagnosed with HCC after SVR. Multivariate analysis showed that male sex, age, and cirrhosis were significant risk factors for HCC incidence. There was no significant difference in the cumulative incidence of HCC after propensity-score matching adjusting for the risk factors of HCC between the two groups. Conclusion: Hemophilia is not a significant risk factor for hepatocarcinogenesis after SVR against HCV.
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- 2022
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21. The effect of the visceral fat area on the predictive accuracy of C‐reactive protein for infectious complications after laparoscopy‐assisted gastrectomy
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Michihisa Iida, Shigeru Takeda, Yuki Nakagami, Shinsuke Kanekiyo, Chiyo Nakashima, Mitsuo Nishiyama, Shin Yoshida, Nobuaki Suzuki, Shigefumi Yoshino, and Hiroaki Nagano
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C‐reactive protein ,gastrectomy ,intra‐abdominal fat ,postoperative complications ,stomach neoplasms ,Surgery ,RD1-811 ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Aim To investigate the influence of visceral fat area on postoperative C‐reactive protein levels and whether it affects its ability to diagnose infectious complications after laparoscopy‐assisted gastrectomy. Methods A total of 435 consecutive patients who underwent laparoscopy‐assisted resection for gastric cancer from 2008 to 2017 were reviewed and divided into four groups according to visceral fat area quartiles. We evaluated the relationship between C‐reactive protein and visceral fat area and whether visceral fat area affects the sensitivity and specificity of C‐reactive protein in diagnosing postoperative infectious complications. Results Postoperative C‐reactive protein levels increased with increasing visceral fat areas at every postoperative assessment. Multiple linear regression revealed that levels on postoperative day 3 significantly positively correlated with visceral fat area. Postoperative day 3 levels also showed moderate accuracy for diagnosing infectious complications (area under the curve, 0.78; sensitivity, 0.86; specificity, 0.65), with an optimal cut‐off of 11.8 mg/dL. The sensitivity for predicting infectious complications was low in the 1st visceral fat area quartile group but high in the 2nd, 3rd, and 4th groups (0.43 vs 1.0 vs 1.0 vs 0.94, respectively). By contrast, the specificity was high in the 1st and 2nd group but low in the 3rd and 4th (0.84 vs 0.70 vs 0.54 vs 0.48, respectively). Conclusion Visceral fat area positively correlated with postoperative C‐reactive protein levels and this affected its accuracy in diagnosing infectious complications. A uniform C‐reactive protein cut‐off may not provide accurate predictions in patients with more extreme visceral fat areas.
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- 2020
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22. Anti-cancer activity of amorphous curcumin preparation in patient-derived colorectal cancer organoids
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Mohamed Elbadawy, Kimika Hayashi, Hiromi Ayame, Yusuke Ishihara, Amira Abugomaa, Makoto Shibutani, Shim-Mo Hayashi, Shoichi Hazama, Hiroko Takenouchi, Masao Nakajima, Ryouichi Tsunedomi, Nobuaki Suzuki, Hiroaki Nagano, Yuta Shinohara, Masahiro Kaneda, Hideyuki Yamawaki, Tatsuya Usui, and Kazuaki Sasaki
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Colorectal cancer ,Amorphous curcumin ,Chemotherapy ,Organoid ,CSCs ,Cell cycle ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Despite its adverse effects, chemotherapy is generally used for the treatment of colorectal cancer (CRC). Development of supplement preparations targeting cancer stem cells (CSCs) that cause distant metastasis and drug resistance is required. Although curcumin is known to have anti-tumor, hepatoprotective, and hypoglycemic-like actions, its low water solubility, oral absorption, and bioavailability impede its therapeutic uses. Patient-derived organoid cultures can recapitulate heterogeneity, epithelial structures, and molecular imprints of their parental tissues. In the present study, anti-carcinogenic properties of amorphous curcumin (AC), a compound with improved solubility and bioavailability, were evaluated against human CRC organoids. Treatment with AC inhibited the cell viability of CRC organoids in a concentration-dependent manner. AC arrested the cell cycle of CRC organoids and induced apoptosis. AC inhibited phosphorylation of ERK. Expression of downstream signals of ERK, namely c-MYC and cyclin-D1, were inhibited. Expressions of CSC markers, CD44, LGR5, and CD133, were declined in the AC-treated CRC organoids. The combinational treatment of CRC organoids with AC and anti-cancer drugs, oxaliplatin, 5-FU, or irinotecan showed a synergistic activity. In vivo, AC decreased the tumor growth of CRC organoids in mice with the induction of necrotic lesions. In conclusion, AC diminished the cell viability of CRC organoids through the inhibition of proliferation-related signals and CSC marker expression in addition to arresting the cell cycle. Collectively, these data suggest the value of AC as a promising supplement that could be used in combination with anti-cancer drugs to prevent the recurrence and metastasis of CRC.
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- 2021
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23. Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study
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Bernhard Mlecnik, Toshihiko Torigoe, Gabriela Bindea, Boryana Popivanova, Mingli Xu, Tomonobu Fujita, Shoichi Hazama, Nobuaki Suzuki, Hiroaki Nagano, Kiyotaka Okuno, Yoshihiko Hirohashi, Tomohisa Furuhata, Ichiro Takemasa, Prabhudas Patel, Hemangini Vora, Birva Shah, Jayendrakumar B. Patel, Kruti N. Rajvik, Shashank J. Pandya, Shilin N. Shukla, Yili Wang, Guanjun Zhang, Takayuki Yoshino, Hiroya Taniguchi, Carlo Bifulco, Alessandro Lugli, Jiun-Kae Jack Lee, Inti Zlobec, Tilman T. Rau, Martin D. Berger, Iris D. Nagtegaal, Elisa Vink-Börger, Arndt Hartmann, Carol I. Geppert, Julie Kolwelter, Susanne Merkel, Robert Grützmann, Marc Van den Eynde, Anne Jouret-Mourin, Alex Kartheuser, Daniel Léonard, Christophe Remue, Julia Wang, Prashant Bavi, Michael H. A. Roehrl, Pamela S. Ohashi, Linh T. Nguyen, SeongJun Han, Heather L. MacGregor, Sara Hafezi-Bakhtiari, Bradly G. Wouters, Giuseppe V. Masucci, Emilia Andersson, Eva Zavadova, Michal Vocka, Jan Spacek, Lubos Petruzelka, Bohuslav Konopasek, Pavel Dundr, Helena Skalova, Kristyna Nemejcova, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Gennaro Ciliberto, Michele Maio, Luigi Laghi, Fabio Grizzi, Florence Marliot, Tessa Fredriksen, Bénédicte Buttard, Lucie Lafontaine, Pauline Maby, Amine Majdi, Assia Hijazi, Carine El Sissy, Amos Kirilovsky, Anne Berger, Christine Lagorce, Christopher Paustian, Carmen Ballesteros-Merino, Jeroen Dijkstra, Carlijn Van de Water, Shannon van Lent-van Vliet, Nikki Knijn, Ana-Maria Mușină, Dragos-Viorel Scripcariu, Francesco M. Marincola, Paolo A. Ascierto, Bernard A. Fox, Franck Pagès, Yutaka Kawakami, and Jérôme Galon
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Immunoscore ,colon cancer ,tumor microenvironment ,immune response ,classification ,prognostic markers ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BACKGROUND: In this study, we evaluated the prognostic value of Immunoscore in patients with stage I–III colon cancer (CC) in the Asian population. These patients were originally included in an international study led by the Society for Immunotherapy of Cancer (SITC) on 2681 patients with AJCC/UICC-TNM stages I–III CC. METHODS: CD3+ and cytotoxic CD8+ T-lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The association of Immunoscore with prognosis was evaluated for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS). RESULTS: Immunoscore stratified Asian patients (n = 423) into different risk categories and was not impacted by age. Recurrence-free rates at 3 years were 78.5%, 85.2%, and 98.3% for a Low, Intermediate, and High Immunoscore, respectively (HR[Low-vs-High] = 7.26 (95% CI 1.75−30.19); p = 0.0064). A High Immunoscore showed a significant association with prolonged TTR, OS, and DFS (p < 0.05). In Cox multivariable analysis stratified by center, Immunoscore association with TTR was independent (HR[Low-vs-Int+High] = 2.22 (95% CI 1.10–4.55) p = 0.0269) of the patient’s gender, T-stage, N-stage, sidedness, and MSI status. A significant association of a High Immunoscore with prolonged TTR was also found among MSS (HR[Low-vs-Int+High] = 4.58 (95% CI 2.27−9.23); p ≤ 0.0001), stage II (HR[Low-vs-Int+High] = 2.72 (95% CI 1.35−5.51); p = 0.0052), low-risk stage-II (HR[Low-vs-Int+High] = 2.62 (95% CI 1.21−5.68); p = 0.0146), and high-risk stage II patients (HR[Low-vs-Int+High] = 3.11 (95% CI 1.39−6.91); p = 0.0055). CONCLUSION: A High Immunoscore is significantly associated with the prolonged survival of CC patients within the Asian population.
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- 2022
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24. A prospective, multicenter, open-label phase III study of emicizumab prophylaxis in patients with acquired hemophilia A
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Midori Shima, Kagehiro Amano, Yoshiyuki Ogawa, Koichiro Yoneyama, Ryoto Ozaki, Ryota Kobayashi, Emiko Sakaida, Makoto Saito, Takashi Okamura, Toshihiro Ito, Norimichi Hattori, Satoshi Higasa, Nobuaki Suzuki, Yoshinobu Seki, and Keiji Nogami
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Hematology - Published
- 2023
25. Anti-VEGF and Anti-EGFR Antibody Therapy on T-Cell Infiltration and TCR Variation in Metastatic Colorectal Cancer
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MING XU, RYOUICHI TSUNEDOMI, KAZUMA KIYOTANI, SHINOBU TOMOCHIKA, KEI FURUYA, MASAO NAKAJIMA, HIROTO MATSUI, YUKIO TOKUMITSU, YOSHITARO SHINDO, SHIN YOSHIDA, MICHIHISA IIDA, NOBUAKI SUZUKI, SHIGERU TAKEDA, TATSUYA IOKA, SHOICHI HAZAMA, and HIROAKI NAGANO
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Cancer Research ,Oncology ,General Medicine - Published
- 2023
26. Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity
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Kou Kanesada, Ryouichi Tsunedomi, Shoichi Hazama, Hiroyuki Ogihara, Yoshihiko Hamamoto, Yoshitaro Shindo, Hiroto Matsui, Yukio Tokumitsu, Shin Yoshida, Michihisa Iida, Nobuaki Suzuki, Shigeru Takeda, Tatsuya Ioka, and Hiroaki Nagano
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Cancer Research ,Oncology ,Radiology, Nuclear Medicine and imaging - Abstract
Irinotecan is a useful anticancer drug for colorectal cancer treatment. UGT1A1*28 and *6 gene polymorphisms are known risk factors for irinotecan-associated toxicity. However, severe adverse effects due to irinotecan have been observed even in patients who do not harbor UGT1A1*28 or *6. We investigated gene polymorphisms in the whole exome to identify useful biomarkers for irinotecan toxicity other than UGT1A.A total of 178 patients with metastatic colorectal cancer (mCRC) and 87 patients with pancreatic cancer were treated with FOLFIRI, FOLFOX, FOLFOXIRI, modified FOLFIRINOX, or gemcitabine plus nab-paclitaxel. Genome-wide screening was performed using whole-exome sequencing (WES), and validation analysis was performed using qPCR with a hydrolysis probe.Using WES after a doublet chemotherapy regimen comprising irinotecan and 5-fluorouracil (n = 15), seven single nucleotide polymorphisms (SNPs) were identified as candidate biomarkers for irinotecan-associated toxicity of neutropenia. Among the seven SNPs, an SNP in R3H domain and coiled-coil containing 1 (R3HCC1; c.919G A, rs2272761) showed a significant association with neutropenia (grade 3) after doublet chemotherapy. Patients receiving irinotecan including triplet chemotherapy, FOLFOXIRI for mCRC (n = 23) or modified FOLFIRINOX for pancreatic cancer (n = 40), also showed significant linear trends between R3HCC1 polymorphism and neutropenia (p = 0.017 and 0.046, respectively). No significant association was observed in patients treated with irinotecan-free regimens, FOLFOX for mCRC (n = 66), and gemcitabine plus nab-paclitaxel for pancreatic cancer (n = 47).Thus, an SNP in the R3HCC1 gene may be a useful biomarker for the toxicity of irinotecan-containing chemotherapy for mCRC and pancreatic cancer.
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- 2022
27. Aberrant X chromosomal rearrangement through multi‐step template switching during sister chromatid formation in a patient with severe hemophilia A
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Mahiru Tokoro, Shogo Tamura, Nobuaki Suzuki, Misaki Kakihara, Yuna Hattori, Koya Odaira, Sachiko Suzuki, Akira Takagi, Akira Katsumi, Fumihiko Hayakawa, Shuichi Okamoto, Atsuo Suzuki, Takeshi Kanematsu, Tadashi Matsushita, and Tetsuhito Kojima
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chromosomal rearrangement ,F8 ,FoSTeS/MMBIR ,hemophilia A ,homologous recombination ,inversion ,Genetics ,QH426-470 - Abstract
Abstract Background Hemophilia A (HA) is an X‐linked recessive bleeding disorder caused by pathogenic variants of the coagulation factor VIII gene (F8). Half of the patients with severe HA have a recurrent inversion in the X chromosome, that is, F8 intron 22 or intron 1 inversion. Here, we characterized an abnormal F8 due to atypical complex X chromosome rearrangements in a Japanese patient with severe HA. Methods Recurrent F8 inversions were tested with inverse shifting‐PCR. The genomic structure was investigated using PCR‐based direct sequencing or quantitative PCR. Results The proband's X chromosome had a 119.5 kb insertion, a reverse duplex of an extragenic sequence on the F8 telomere region into the F8 intron 1 with two breakpoints. The telomeric breakpoint was a joining from the F8 intron 1 to the inverted FUNDC2 via a two‐base microhomology, and the centromeric breakpoint was a recombination between F8 intron 1 homologous sequences. The rearrangement mechanism was suggested as a multi‐step rearrangement with template switching such as fork stalling and template switching (FoSTeS)/microhomology‐mediated break‐induced replication (MMBIR) and/or homologous sequence‐associated recombination during a sister chromatid formation. Conclusion We identified the aberrant X chromosome with a split F8 due to a multi‐step rearrangement in a patient with severe HA.
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- 2020
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28. Laparoscopic total biopsy for suspected gallbladder cancer: A case series
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Yukio Tokumitsu, Yoshitaro Shindo, Hiroto Matsui, Satoshi Matsukuma, Masao Nakajima, Shin Yoshida, Michihisa Iida, Nobuaki Suzuki, Shigeru Takeda, and Hiroaki Nagano
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gallbladder bed dissection ,gallbladder cancer ,laparoscopic surgery ,Total biopsy ,whole‐layer cholecystectomy ,Medicine - Abstract
Abstract Background and aims Imaging diagnosis of gallbladder cancer remains difficult to achieve preoperatively. We developed a novel approach based on laparoscopic whole‐layer cholecystectomy (LWLC) and laparoscopic gallbladder bed dissection (LGBD) for total biopsy, for ultimately determining the optimal treatment strategy for suspected gallbladder cancer detected on preoperative imaging. Here, we describe a case series of patients who underwent this procedure at our institution. Methods We retrospectively examined clinicopathological data of consecutive patients with suspected gallbladder carcinoma at Yamaguchi University Graduate School of Medicine from September 2016 to July 2018 on which a laparoscopic approach was used. Preoperative imaging findings suggestive of gallbladder cancer were defined as follows: elevated lesion >10 mm in diameter, increasing tumor size over time compared with the previous imaging, sessile lesion, irregular wall thickness lesion mimicking cancer, elevated lesion with dense enhancement, or positive results on fluorodeoxyglucose positron emission tomography. LWLC was performed for early‐stage or suspected malignant lesions without liver invasion, and LGBD was performed for lesions with an unclear border between the gallbladder and the liver. When postoperative pathological examination revealed the presence of gallbladder cancer invading into the subserosal layer, additional gallbladder bed resection and regional lymphadenectomy were considered. Patient characteristics, perioperative findings, pathological findings, and postoperative outcomes of patients who underwent LWLC or LGBD were reviewed retrospectively, and the short‐term outcomes of the laparoscopic approach were analyzed. Results Fifteen consecutive patients were included in the study. The median age of the patients was 63 years (IQR 42‐76 years); 7 patients were males. We performed LWLC in 12 cases and LBGD in 3 cases. Median (IQR) operation time was 159 (140‐193) min and median blood loss was 10 (5–30) mL. No bile leakage caused by intraoperative perforation of the gallbladder was seen. Median hospital stay was 7 (5–9) days. Only one patient developed postoperative complications (abdominal abscess). Histologically, gallbladder cancer was diagnosed in five cases (pT1a, n = 2; pT2, n = 3), and two of the pT2 patients underwent additional open surgery. Conclusions Our laparoscopic‐based approach for suspected gallbladder cancer might represent a safe strategy and could play an important role in defining the optimal treatment strategy.
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- 2020
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29. Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors
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Shuichi Okamoto, Nobuaki Suzuki, Atsuo Suzuki, Sachiko Suzuki, Shogo Tamura, Mochihito Suzuki, Nobunori Takahashi, Toshihisa Kojima, Takeshi Kanematsu, Tetsuhito Kojima, Hitoshi Kiyoi, Naoki Ishiguro, and Tadashi Matsushita
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factor viii inhibitors ,surgery ,hemophilia therapy ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
We managed perioperative hemostasis for a 72-year-old man with hemophilia A and low inhibitor titers (3 BU/mL), who underwent osteosynthesis for supracondylar fracture of the left humerus. He was treated perioperatively using the combination of high doses of factor VIII (FVIII) with recombinant human Factor VIII Fc fusion protein (rFVIIIFc), followed by emicizumab. On the day of surgery (day 0), he was administered bolus infusion of 150 IU/kg rFVIIIFc, followed by continuous infusion at a dose of 4 IU/kg/h. Emicizumab, 3 mg/kg, was injected subcutaneously once a week, on days 5, 12, 19, and 26. Inhibitors were detected on day 6 at a titer of 4 BU/mL and FVIII:C decreased to below assay sensitivity limits on day 10. The rate of increase in inhibitor titers was high, with inhibitors increasing to 343.4 BU/mL on day 14. The transition of thrombin production by thrombin generation assay (TGA) showed temporary decrease in thrombin production on day 7, although it was restored by day 10, i.e., five days after commencement of emicizumab therapy. Rotational thromboelastometry displayed consistent results with TGA, showing that clotting time was prolonged and the alpha angle decreased to less than measurable levels on day 6, although they were improved by day 10. There were no bleeding-related events or other adverse events throughout the perioperative period. In conclusion, emicizumab was effective for the management of perioperative hemostasis after development of an anamnestic response in a patient with hemophilia A with inhibitors. Combination therapy with high doses of FVIII followed by emicizumab could be a workable alternative for patients with hemophilia A with inhibitors.
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- 2019
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30. VWF‐Gly2752Ser, a novel non‐cysteine substitution variant in the CK domain, exhibits severe secretory impairment by hampering C‐terminal dimer formation
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Shuichi Okamoto, Shogo Tamura, Naomi Sanda, Koya Odaira, Yuri Hayakawa, Masato Mukaide, Atsuo Suzuki, Takeshi Kanematsu, Fumihiko Hayakawa, Akira Katsumi, Hitoshi Kiyoi, Tetsuhito Kojima, Tadashi Matsushita, and Nobuaki Suzuki
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Protein Domains ,von Willebrand Factor ,Cystine ,Humans ,Cysteine ,Hematology ,Protein Multimerization ,von Willebrand Disease, Type 3 - Abstract
Background: Von Willebrand factor (VWF) is a multimeric glycoprotein that plays important roles in hemostasis and thrombosis. C-terminal interchain-disulfide bonds in the cystine knot (CK) domain are essential for VWF dimerization. Previous studies have reported that missense variants of cysteine in the CK domain disrupt the intrachain-disulfide bond and cause type 3 von Willebrand disease (VWD). However, type 3 VWD-associated noncysteine substitution variants in the CK domain have not been reported. Objective: To investigate the molecular mechanism of a novel non-cysteine variant in the CK domain, VWF c.8254 G>A (p.Gly2752Ser), which was identified in a patient with type 3 VWD as homozygous. Methods: Genetic analysis was performed by whole exome sequencing and Sanger sequencing. VWF multimer analysis was performed using SDS-agarose electrophoresis. VWF production and subcellular localization were analyzed using ex vivo endothelial colony forming cells (ECFCs) and an in vitro recombinant VWF (rVWF) expression system. Results: The patient was homozygous for VWF-Gly2752Ser. Plasma VWF enzyme-linked immunosorbent assay showed that the VWF antigen level of the patient was 1.2% compared with healthy subjects. A tiny amount of VWF was identified in the patient's ECFC. Multimer analysis revealed that the circulating VWF-Gly2752Ser presented only low molecular weight multimers. Subcellular localization analysis of VWF-Gly2752Ser-transfected cell lines showed that rVWF-Gly2752Ser was severely impaired in its ER-to-Golgi trafficking. Conclusion: VWF-Gly2752Ser causes severe secretory impairment because of its dimerization failure. This is the first report of a VWF variant with a noncysteine substitution in the CK domain that causes type 3 VWD.
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- 2022
31. Comparison of two primer-probe sets of Fusobacterium nucleatum using droplet digital polymerase chain reaction for the detection of colorectal neoplasia from faecal samples
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Yuko Yamaoka, Mai Sasai, Yutaka Suehiro, Shinichi Hashimoto, Atsushi Goto, Naoki Yamamoto, Nobuaki Suzuki, Shingo Higaki, Ikuei Fujii, Chieko Suzuki, Toshihiko Matsumoto, Tomomi Hoshida, Michiko Koga, Takeya Tsutsumi, Lay A Lim, Yasuo Matsubara, Shinobu Tomochika, Shin Yoshida, Shoichi Hazama, Hiroshi Yotsuyanagi, Hiroaki Nagano, Isao Sakaida, Taro Takami, and Takahiro Yamasaki
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Adenoma ,Feces ,Fusobacterium nucleatum ,Clinical Biochemistry ,Humans ,General Medicine ,Colorectal Neoplasms ,Real-Time Polymerase Chain Reaction - Abstract
Background: Although faecal DNA testing of Fusobacterium nucleatum ( Fn) is expected to be useful for colorectal neoplasia detection, there is no standardized quantification method of Fn. We performed this study to establish a possible standardized method. Methods: In this study, 322 participants including 71 subjects without colorectal neoplasia (control group), 31 patients with non-advanced colorectal adenoma, 93 patients with advanced colorectal adenoma, and 127 patients with colorectal cancer were enrolled. Faecal Fn were quantified by droplet digital PCR (ddPCR) using two PCR primer-probe sets reported previously that are tentatively named Fn1 and Fn2. Fn1 has been used in ddPCR by us and Fn2 has been widely used in quantitative real-time PCR. Results: The Fn copy number using Fn1 was five times higher than that using Fn2, with a linear relationship shown between them. Receiver operating characteristic curve analysis showed the area under the curve (AUC) to be almost the same between Fn1 and Fn2 in discriminating between the control group and the colorectal cancer group (AUC = 0.81 and 0.81, respectively), and between the control/non-advanced colorectal adenoma group and the advanced colorectal adenoma/colorectal cancer group (AUC = 0.74 and 0.74, respectively). Conclusions: As the diagnostic performance was quite similar between Fn1 and Fn2, ddPCR-based Fn testing using Fn1 and Fn2 could be a possible standardized method for a colorectal neoplasia screening test, considering that Fn levels quantified by Fn1 are about five times higher than those by Fn2.
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- 2022
32. Multiplex Polymerase Chain Reaction Method with Species-specific Primers for Differentiation of Two Closely Related Fish Species, Beryx splendens and B. mollis (Actinopterygii: Beryciformes)
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Kazuya NISHIDA, Satoru N. CHIBA, Kay SAKUMA, Ryouichi HIGASHI, Nobuaki SUZUKI, Mai MIYAMOTO, Shiroh YONEZAKI, Kouichi HOSHINO, and Kota SAWADA
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Ecology ,Animal Science and Zoology ,Agronomy and Crop Science ,Biotechnology - Published
- 2022
33. Efficacy of Staging Laparoscopy in Patients With Pancreatic Cancer: A Single Center Prospective Cohort Study.
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YOSHITARO SHINDO, YUKIO TOKUMITSU, HIROTO MATSUI, MASAO NAKAJIMA, YUTA KIMURA, MICHIHISA IIDA, NOBUAKI SUZUKI, SHIGERU TAKEDA, TATSUYA IOKA, and HIROAKI NAGANO
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PANCREATIC cancer treatment ,LAPAROSCOPY ,PANCREATECTOMY ,CANCER chemotherapy ,BLOOD loss estimation - Abstract
Background/Aim: Staging laparoscopy (SL) for pancreatic cancer (PC) is considered useful to improve accuracy of staging and resectability. However, given the current accuracy of preoperative imaging, the routine application of SL remains unclear. Therefore, we aimed to investigate the importance of SL in patients with PC without radiological distant metastasis. Patients and Methods: This was a prospective, cohort, observational study. SL was performed in all patients with PC without radiological distant metastasis before pancreatectomy or chemotherapy at the Yamaguchi University Hospital. Results: Between July 2020 and March 2023, 55 patients underwent SL with peritoneal cytology. The median age was 71, with 53% male patients. SL revealed occult metastasis in six (11%) patients including positive peritoneal cytology (n=6), and peritoneal dissemination (n=1). The resectability of unresectable locally advanced (UR-LA) was associated with a significantly increased risk of occult metastasis (p=0.0211). The median operative time was 40 min, and the median volume of blood loss was 3 ml. There were no severe complications (Clavien-Dindo III or higher). Conclusion: SL with peritoneal cytology regardless of previous abdominal surgery is safe and effective to determine accurate staging. Therefore, SL with peritoneal cytology should be considered for patients with PC without radiological distant metastasis, especially in those with UR-LA. [ABSTRACT FROM AUTHOR]
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- 2023
- Full Text
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34. IL-6 Levels Correlate with Prognosis and Immunosuppressive Stromal Cells in Patients with Colorectal Cancer
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Tsunenori Yamamoto, Ryouichi Tsunedomi, Masao Nakajima, Nobuaki Suzuki, Shin Yoshida, Shinobu Tomochika, Ming Xu, Yuki Nakagami, Hiroto Matsui, Yukio Tokumitsu, Yoshitaro Shindo, Yusaku Watanabe, Michihisa Iida, Shigeru Takeda, Shoichi Hazama, Tsuyoshi Tanabe, Tatsuya Ioka, Yoshinobu Hoshii, Akifumi Kiyota, Hitoshi Takizawa, Yutaka Kawakami, Tomio Ueno, and Hiroaki Nagano
- Subjects
Oncology ,Surgery - Published
- 2023
35. ASO Visual Abstract: Interleukin-6 Levels Correlate with Prognosis and Immunosuppressive Stromal Cells in Patients with Colorectal Cancer
- Author
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Tsunenori Yamamoto, Ryouichi Tsunedomi, Masao Nakajima, Nobuaki Suzuki, Shin Yoshida, Shinobu Tomochika, Ming Xu, Yuki Nakagami, Hiroto Matsui, Yukio Tokumitsu, Yoshitaro Shindo, Yusaku Watanabe, Michihisa Iida, Shigeru Takeda, Shoichi Hazama, Tsuyoshi Tanabe, Tatsuya Ioka, Yoshinobu Hoshii, Akifumi Kiyota, Hitoshi Takizawa, Yutaka Kawakami, Tomio Ueno, and Hiroaki Nagano
- Subjects
Oncology ,Surgery - Published
- 2023
36. Comparison of kinship-identification methods for robust stock assessment using close-kin mark--recapture data for Pacific bluefin tuna
- Author
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Yohei Tsukahara, Reiichiro Nakamichi, Aiko Matsuura, Tetsuya Akita, Atushi Fujiwara, and Nobuaki Suzuki
- Abstract
There have been many attempts to understand population dynamics in fishery resources such as tuna species using an integrated-analysis model with multiple data sources. However, estimating the absolute abundance level in practical stock assessments remains challenging. The close-kin mark–recapture (CKMR) method provides information about the number of adults in a population utilizing close-kinship pairs (i.e., parent–offspring, full-sibling, or half-sibling pairs) identified based on statistical methods that employ genetic markers. To introduce the CKMR method into the stock assessment by integrated analysis, it is necessary to clarify the potential errors obtained from the uncertainties in the CKMR method and other data sources. In this paper, we applied three methods of kinship identification for samples from the wild Pacific bluefin tuna population using genome-wide DNA markers to determine the potential errors in statistical kinship estimates. Herein, one method used a random-forest classification algorithm called fraRF that employed pairwise identity-by-descent values. The other two methods were CKMRsim and COLONY. Comparisons among these three methods revealed differences in the numbers of inferred kinship pairs, especially for sibling relationships. The differences among the three methods seem to occur mainly from uncertainty of the kinship identification in the CKMR method. Therefore, this result provides an understanding of ways to incorporate the CKMR method into the integrated analysis model with the possible CKMR errors.
- Published
- 2023
37. Locus-specific EPIC-PCR primers for four distinct calmodulin genes of the Pacific bluefin tuna Thunnus orientalis (Temminck & Schlegel, 1844)
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Seinen Chow, Nobuaki Suzuki, Yoji Nakamura, Motoshige Yasuike, Kenji Saitoh, and Takashi Yanagimoto
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Thunnus orientalis ,Four calmodulin genes ,Locus-specific primers ,Cross-species amplification ,DNA marker ,Aquaculture. Fisheries. Angling ,SH1-691 ,Ecology ,QH540-549.5 - Abstract
Abstract Nucleotide sequences of four distinct calmodulin genes (designated as CaM-A to -D) of the Pacific bluefin tuna (Thunnus orientalis) were compared. Nucleotide sequence divergence between the coding regions of four genes ranged from 16.0 to 21.6%, and locus-specific eight primer pairs targeting introns were designed. These primer pairs amplified expected size of fragments in five congeneric tuna species, and utility of these primer pairs was investigated using distant fish species.
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- 2017
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- View/download PDF
38. EFFICACY OF DESENSITIZATION THERAPY FOR ALLERGY TO FACTOR IX CONCENTRATES
- Author
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Nobuaki Suzuki, Takeshi Kanematsu, Mayuko Kishimoto, Naruko Suzuki, Shuichi Okamoto, Shogo Tamura, Hitoshi Kiyoi, and Tadashi Matsushita
- Published
- 2022
39. F9 mRNA splicing aberration due to a deep Intronic structural variation in a patient with moderate hemophilia B
- Author
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Koya Odaira, Fumika Kawashima, Shogo Tamura, Nobuaki Suzuki, Mahiru Tokoro, Yuri Hayakawa, Atsuo Suzuki, Takeshi Kanematsu, Shuichi Okamoto, Akira Takagi, Akira Katsumi, Tadashi Matsushita, Midori Shima, Keiji Nogami, Tetsuhito Kojima, and Fumihiko Hayakawa
- Subjects
Factor IX ,Male ,Mutation ,Humans ,RNA, Messenger ,Hematology ,Hemophilia A ,Hemophilia B ,Introns - Abstract
Hemophilia B (HB) is a hereditary bleeding disorder caused by the genetic variation of the coagulation factor IX (FIX) gene (F9). Several F9 structural abnormalities, including large deletion and/or insertion, have been observed to cause HB development. However, there is limited information available on F9 deep intronic variations. In this study, we report about a novel large deletion/insertion observed in a deep region of F9 intron 1 that causes mRNA splicing abnormalities.The patient was a Japanese male diagnosed with moderate HB (FIX:C = 3.0 IU/dL). The genomic DNA of the patient was isolated from peripheral blood leukocytes. DNA sequences of F9 exons and splice donor/acceptor sites were analyzed via polymerase chain reaction and Sanger sequencing. Variant-affected F9 mRNA aberration and FIX protein production, secretion, and coagulant activity were analyzed by cell-based exon trap and splicing-competent FIX expression vector systems.A 28-bp deletion/476-bp insertion was identified in the F9 intron 1 of a patient with moderate HB. A DNA sequence identical to a part of the inverted HNRNPA1 exon 12 was inserted. Cell-based transcript analysis revealed that this large intronic deletion/insertion disrupted F9 mRNA splicing pattern, resulting in reduction of protein-coding F9 mRNA.A novel deep intronic F9 rearrangement was identified in a Japanese patient with moderate HB. Abnormal F9 mRNA splicing pattern due to this deep intronic structural variation resulted in a reduction of protein-coding F9 mRNA, which probably caused the moderate HB phenotype.
- Published
- 2022
40. First Report on the Use of the Larval Catcher Type Trawl Net for the Efficient Sampling of Juveniles of Two Tuna Species (Thunnus orientalis and T. albacares) in the Offshore Waters of the Nansei Islands, Japan
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Toshiyuki TANABE, Yosuke MIYAZAKI, Kenji NOHARA, Nobuaki SUZUKI, and Takao YOSHIMATSU
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Ecology ,Animal Science and Zoology ,Agronomy and Crop Science ,Biotechnology - Published
- 2022
41. TCR sequencing analysis of cancer tissues and tumor draining lymph nodes in colorectal cancer patients
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Tatsuo Matsuda, Eisaku Miyauchi, Yu-Wen Hsu, Satoshi Nagayama, Kazuma Kiyotani, Makda Zewde, Jae-Hyun Park, Taigo Kato, Makiko Harada, Shimpei Matsui, Masashi Ueno, Kazumasa Fukuda, Nobuaki Suzuki, Shoichi Hazama, Hiroaki Nagano, Hiroya Takeuchi, Wickii T. Vigneswaran, Yuko Kitagawa, and Yusuke Nakamura
- Subjects
t cell receptor ,colorectal cancer ,lymph node ,immunogenomics ,immunotherapy ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Tumor draining lymph nodes (TDLNs) are located in the routes of lymphatic drainage from a primary tumor and have the highest risk of metastasis in various types of solid tumors. TDLNs are also considered as a tissue to activate the antitumor immunity, where antigen-specific effector T cells are generated. However, T cell receptor (TCR) repertoires in TDLNs have not been well characterized. We collected 23 colorectal cancer tumors with 203 lymph nodes with/without metastatic cancer cells (67 were metastasis-positive and the remaining 136 were metastasis-negative) and performed TCR sequencing. Metastasis-positive TDLNs showed a significantly lower TCR diversity and shared TCR clonotypes more frequently with primary tumor tissues compared to metastasis-negative TDLNs. Principal component analysis indicated that TDLNs with metastasis showed similar TCR repertoires. These findings suggest that cancer-reactive T cell clones could be enriched in the metastasis-positive TDLNs.
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- 2019
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42. Phase I study of a novel therapeutic vaccine as perioperative treatment for patients with surgically resectable hepatocellular carcinoma: The YCP02 trial
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Masao Nakajima, Shoichi Hazama, Yukio Tokumitsu, Yoshitaro Shindo, Hiroto Matsui, Satoshi Matsukuma, Yuki Nakagami, Koji Tamada, Keiko Udaka, Michiie Sakamoto, Akira Saito, Yasunari Kouki, Toshinari Uematsu, Ming Xu, Michihisa Iida, Ryouichi Tsunedomi, Nobuaki Suzuki, Shigeru Takeda, Tatsuya Ioka, Shun Doi, and Hiroaki Nagano
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Infectious Diseases ,Hepatology - Published
- 2023
43. The Recent Development of the Surgical Treatment for Hepatocellular Carcinoma
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Masao Nakajima, Yukio Tokumitsu, Yoshitaro Shindo, Hiroto Matsui, Satoshi Matsukuma, Michihisa Iida, Nobuaki Suzuki, Shigeru Takeda, Tatsuya Ioka, and Hiroaki Nagano
- Subjects
hepatocellular carcinoma ,surgical indication ,portal vein tumor thrombus ,hepatic vein tumor thrombus ,multiple tumors ,multidisciplinary treatment ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
The optimal treatment for hepatocellular carcinoma (HCC) should be selected based on tumor conditions, liver functional reserve, and performance status. Surgical treatment, such as liver resection and liver transplantation, is the most favorable treatment method; however, its indication criteria differ according to each country’s guidelines. In Western countries, liver resection is indicated only for early-stage HCC patients with Barcelona-Clinic Liver Cancer staging classification (BCLC) 0/A. While in Asian countries, liver resection is one of the treatment options for advanced HCC, such as BCLC B/C. Recently, the treatment of HCC is about to enter a drastic transitional period. It started with the widespread use of minimally invasive surgery for HCC, followed by a high rate of hepatitis C virus eradication with the advent of direct acting antivirals and developing a multidisciplinary treatment for highly advanced HCC. As a result, the importance of liver resection for HCC is increasing, and it is time to reconsider the criteria for selecting treatment methods for HCC patients. This article outlines current topics in the surgical treatment of HCC.
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- 2021
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44. Efficacy of Preoperative Bilateral Thoracic Paravertebral Block in Cardiac Surgery Requiring Full Heparinization: A Propensity-Matched Study
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Toshinori Kasai, Yasushi Kudo, Takaharu Tokita, Yuri Sato, Masaaki Naganuma, Shinya Masuda, Nobuaki Suzuki, and K. Nagaya
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Adult ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Fentanyl ,03 medical and health sciences ,0302 clinical medicine ,Aortic valve replacement ,030202 anesthesiology ,Interquartile range ,medicine ,Humans ,Paravertebral Block ,Cardiac Surgical Procedures ,Retrospective Studies ,Pain, Postoperative ,business.industry ,Nerve Block ,Retrospective cohort study ,medicine.disease ,Cardiac surgery ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,Anesthesia ,Cohort ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug ,Artery - Abstract
OBJECTIVES To assess the efficacy of preoperative bilateral paravertebral block (PVB) with general anesthesia (GA) in contributing to early extubation and decreasing opioid consumption in cardiac surgery. DESIGN A propensity score-matched retrospective study. SETTING A single tertiary medical center between January 2018 and December 2020. PARTICIPANTS Adult patients undergoing isolated first-time aortic valve replacement and coronary artery bypass grafting with full sternotomy. INTERVENTIONS A cohort of 44 patients who received PVB with GA (PVB group) was matched with 44 patients who underwent similar surgery with GA only (GA only group). MEASUREMENTS AND MAIN RESULTS The completion rate of extubation in the operating room was significantly greater in the PVB group (65.9%) than in the GA only group (43.2%; p = 0.032). The completion rate of extubation within eight hours after surgery also was significantly greater in the PVB group (86.4%) than in the GA only group (68.2%; p = 0.042). The median amount of intraoperative fentanyl administered was significantly less in the PVB group (4.8 µg/kg; interquartile range [IQR], 3.3-7.2) than in the GA only group (8.4 µg/kg; IQR, 5.4-12.7; p < 0.001). The median amount of postoperative fentanyl administered was significantly less in the PVB group (6.8 µg/kg; IQR, 3.9-10.6) than in the GA only group (8.1 µg/kg; IQR, 6.2-15.9; p = 0.012). CONCLUSIONS This study demonstrated that preoperative bilateral PVB combined with GA contributed to early extubation in isolated first-time aortic valve replacement and coronary artery bypass grafting and in the reduction of intraoperative and postoperative fentanyl consumption.
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- 2022
45. Basic and clinical aspects of anti-tissue factor pathway inhibitor (TFPI)
- Author
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Nobuaki SUZUKI
- Published
- 2022
46. Chromogenic assay in hemopihilia treatment
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Mika OGAWA, Atsuo SUZUKI, Nobuaki SUZUKI, and Takayuki NAKAYAMA
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- 2022
47. A method for identifying the manufacturer of sleeping pills used in crime via the analysis of pharmaceutical additives
- Author
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Nobuaki Suzuki, Syuji Okuyama, Yuki Iwai, and Motoyasu Sato
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General Medicine - Published
- 2022
48. Association between Polyunsaturated Fatty Acid and Reactive Oxygen Species Production of Neutrophils in the General Population
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Nobuaki Suzuki, Kaori Sawada, Ippei Takahashi, Motoko Matsuda, Shinji Fukui, Hidemasa Tokuyasu, Hiroyasu Shimizu, Junichi Yokoyama, Arata Akaike, and Shigeyuki Nakaji
- Subjects
polyunsaturated fatty acids ,arachidonic acid ,dihomo gamma linolenic acid ,reactive oxygen species ,cross-sectional study ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Little is known about the relationship between polyunsaturated fatty acids (PUFAs) and reactive oxygen species (ROS) in the general population. Therefore this study aimed to describe the association of PUFAs with ROS according to age and sex in the general population and to determine whether PUFA levels are indicators of ROS. This cross-sectional study included 895 participants recruited from a 2015 community health project. Participants were divided into 6 groups based on sex and age (less than 45 years old (young), aged 45–64 years (middle-aged), and 65 years or older (old)) as follows: male, young (n = 136); middle-aged (n = 133); old (n = 82); female, young (n = 159); middle-aged (n = 228); and old (n = 157). The PUFAs measured were arachidonic acid (AA), dihomo gamma linolenic acid (DGLA), AA/DGLA ratio, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ROS considered in the analysis were basal ROS and stimulated ROS levels. Multiple linear analyses showed: (1) significant correlations between PUFA levels, especially DGLA and AA/DGLA ratio, and neutrophil function in the young and middle-aged groups; (2) no significant correlations in old age groups for either sex. Because PUFAs have associated with the ROS production, recommendation for controlled PUFA intake from a young age should be considered.
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- 2020
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49. Feeding ecology of juvenile Pacific bluefin tuna
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Takuya Sato, Ken-ichi Nakamura, Atsushi Nishimoto, Atsushi Tawa, Taketoshi Kodama, Nobuaki Suzuki, Hiroshi Ashida, and Hiroshige Tanaka
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Ecology ,Aquatic Science ,Oceanography ,Ecology, Evolution, Behavior and Systematics - Abstract
The feeding ecology of juvenile Pacific bluefin tuna (PBF) Thunnus orientalis in the Sea of Japan was examined to better understand the survival process before fishery recruitment. Stomach content analysis showed that the main prey items were fish, especially Japanese anchovy Engraulis japonicus, cephalopods, mainly small squid Enoploteuthis chunii, and copepods. In addition, although both fish prey and cephalopods were important for large juveniles (100–300-mm fork length, FL), the stomach contents of small juveniles (40–99 mm FL) mainly included fish prey. The strong possibility of cannibalism was also suggested, although its contribution to total food consumption was limited. The size of fish prey increased significantly with the FL of PBF. Nitrogen isotope ratios (i.e. δ15N) also increased with increasing FL (12–227 mm), suggesting that the trophic level increases rapidly during the juvenile stage because of the active feeding on fish by PBF. Such feeding habits, especially feeding on fish, would be essential to achieve a high growth rate and would therefore be associated with the survival of juvenile PBF before recruitment in the Sea of Japan. In addition, PBF exhibited a decrease in stomach fullness during the night-time, and their estimated gastric evacuation rate was 0.36 h–1.
- Published
- 2021
50. Successful ligation of posterior tibial vein aneurysm performed according to intraoperative venography results
- Author
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Shinya Masuda, Nobuaki Suzuki, Yasushi Kudo, K. Nagaya, and Masaaki Naganuma
- Subjects
Innovative technique ,medicine.medical_specialty ,RD1-811 ,Deep vein ,Venography ,Veins ,Aneurysm ,Deep vein thrombosis ,medicine ,Diseases of the circulatory (Cardiovascular) system ,cardiovascular diseases ,medicine.diagnostic_test ,business.industry ,Pulmonary embolism ,Successful ligation ,medicine.disease ,Thrombosis ,Surgery ,medicine.anatomical_structure ,medicine.vein ,RC666-701 ,cardiovascular system ,Posterior tibial vein ,Cardiology and Cardiovascular Medicine ,Ligation ,business - Abstract
A 23-year-old woman was diagnosed with a posterior tibial vein aneurysm that had resulted in deep vein thrombosis and a pulmonary embolism. The patient responded well to anticoagulation therapy, and surgical resection was planned to prevent recurrence. She was scheduled to undergo tangential aneurysmectomy and lateral venorrhaphy. However, the aneurysm could not be completely exposed because of adhesions. Therefore, venography was performed to identify the inflow and outflow vessels, which were ligated because an accessory venous communication was identified. Intraoperative venography can aid in the selection of simple ligation or reconstruction of a venous communication for the treatment of posterior tibial vein aneurysms.
- Published
- 2021
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