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Article ; Online: Adjuvant Chemotherapy With S-1 Plus Docetaxel

Yamamoto, Masaaki / Omori, Takeshi / Shinno, Naoki / Hara, Hisashi / Mukai, Yosuke / Sugase, Takahito / Takeoka, Tomohira / Mikamori, Manabu / Kanemura, Takashi / Hasegawa, Shinichiro / Akita, Hirofumi / Haraguchi, Naotsugu / Nishimura, Junichi / Wada, Hiroshi / Matsuda, Chu / Yasui, Masayoshi / Miyata, Hiroshi / Ohue, Masayuki

Anticancer research

2023 Volume 43, Issue 11, Page(s) 5015–5024

Abstract: Background/aim: The Japanese Gastric Cancer Treatment Guidelines recommend doublet chemotherapy (S ... 1 plus another chemotherapy) over S-1 alone for patients with pStage III gastric cancer ... and survival outcomes of docetaxel plus S-1 (DS) and S-1 plus oxaliplatin (SOX) therapies ...

Abstract	Background/aim: The Japanese Gastric Cancer Treatment Guidelines recommend doublet chemotherapy (S-1 plus another chemotherapy) over S-1 alone for patients with pStage III gastric cancer who underwent radical gastrectomy. However, no consensus exists on adjuvant regimens for patients with pStage III gastric cancer. Therefore, we conducted a comparative study to evaluate the tolerability, safety, and survival outcomes of docetaxel plus S-1 (DS) and S-1 plus oxaliplatin (SOX) therapies as adjuvant chemotherapy for patients with pStage III gastric cancer. Patients and methods: We retrospectively collected data from consecutive patients with gastric cancer who underwent gastrectomy and received DS or SOX therapies postoperatively at the Osaka International Cancer Institute between December 2016 and December 2021. We conducted a propensity score matching analysis to balance clinical backgrounds. Results: Eighty patients who met the eligibility criteria were analyzed. After matching, 40 patients were included in the study (20 each in the DS and SOX groups). No significant adverse events were observed. The mean ratios of the delivered dose to the planned dose were 74.1% and 86.6% for S-1 and docetaxel in the DS group, respectively, and 75.8% and 76.9% for S-1 and oxaliplatin in the SOX group, respectively. No significant differences were found in recurrence-free and overall survival between the DS and SOX groups (p=0.688 and p=0.772, respectively). Conclusion: DS and SOX therapies as adjuvants were safe and manageable for patients with pStage III gastric cancer who underwent radical gastrectomy. No significant differences were found in prognosis between the two therapies.
MeSH term(s)	Humans ; Docetaxel ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/surgery ; Oxaliplatin ; Retrospective Studies ; Chemotherapy, Adjuvant ; Adjuvants, Immunologic
Chemical Substances	Docetaxel (15H5577CQD) ; Oxaliplatin (04ZR38536J) ; Adjuvants, Immunologic
Language	English
Publishing date	2023-11-01
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.16700
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Article ; Online: Phase II study of S-1 plus oxaliplatin 130 mg/m

Kito, Yosuke / Machida, Nozomu / Kawai, Sadayuki / Hamauchi, Satoshi / Tsushima, Takahiro / Todaka, Akiko / Yokota, Tomoya / Yamazaki, Kentaro / Fukutomi, Akira / Onozawa, Yusuke / Tsuji, Kunihiro / Doyama, Hisashi / Haraguchi, Yutaka / Nakashima, Koji / Kunieda, Kenji / Taku, Keisei / Mori, Keita / Yasui, Hirofumi

International journal of clinical oncology

2018 Volume 23, Issue 6, Page(s) 1084–1089

Abstract: Purpose: Although oxaliplatin 130 mg/m: Methods: Patients with unresectable or recurrent gastric adenocarcinoma, no previous chemotherapy, and Eastern Cooperative Oncology Group Performance Status of 0-1 were treated with SOX130. The primary endpoint ...

Abstract	Purpose: Although oxaliplatin 130 mg/m Methods: Patients with unresectable or recurrent gastric adenocarcinoma, no previous chemotherapy, and Eastern Cooperative Oncology Group Performance Status of 0-1 were treated with SOX130. The primary endpoint was the 3-cycle completion rate, defined as the proportion of patients who completed the first three cycles with ≥ 80% relative dose intensity of oxaliplatin. Results: Twenty-five patients were enrolled from April 2015 to 2016. The 3-cycle completion rate was 72.0% (90% confidence interval: 53.8-86.1), which was higher than the predetermined threshold rate of 50%. With the median number of cycles being 6 (range, 1-19+), grade 3 or 4 adverse events occurred in 10 patients (40%). Major grade 3 adverse events were anorexia (24%), thrombocytopenia (16%), and neutropenia (12%). No febrile neutropenia or treatment-related deaths occurred. Among 12 patients with measurable lesions, the overall response rate was 58.3%. Median progression-free and overall survival were 5.7 months (95% confidence interval 2.9-8.5) and 13.1 months (95% confidence interval 7.4-19.0), respectively. Conclusion: Results indicated that SOX130 was feasible in Japanese patients with advanced gastric cancer.
MeSH term(s)	Adenocarcinoma/drug therapy ; Adenocarcinoma/mortality ; Adenocarcinoma/pathology ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Asian Continental Ancestry Group ; Drug Combinations ; Female ; Humans ; Male ; Middle Aged ; Neutropenia/chemically induced ; Oxaliplatin/administration & dosage ; Oxonic Acid/administration & dosage ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/mortality ; Stomach Neoplasms/pathology ; Survival Analysis ; Tegafur/administration & dosage ; Thrombocytopenia/chemically induced ; Treatment Outcome
Chemical Substances	Drug Combinations ; Oxaliplatin (04ZR38536J) ; S 1 (combination) (150863-82-4) ; Tegafur (1548R74NSZ) ; Oxonic Acid (5VT6420TIG)
Language	English
Publishing date	2018-06-21
Publishing country	Japan
Document type	Clinical Trial, Phase II ; Journal Article ; Multicenter Study
ZDB-ID	1400227-9
ISSN	1437-7772 ; 1341-9625
ISSN (online)	1437-7772
ISSN	1341-9625
DOI	10.1007/s10147-018-1308-1
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Article ; Online: Chromatin loading of MCM hexamers is associated with di-/tri-methylation of histone H4K20 toward S phase entry.

Hayashi-Takanaka, Yoko / Hayashi, Yuichiro / Hirano, Yasuhiro / Miyawaki-Kuwakado, Atsuko / Ohkawa, Yasuyuki / Obuse, Chikashi / Kimura, Hiroshi / Haraguchi, Tokuko / Hiraoka, Yasushi

Nucleic acids research

2021 Volume 49, Issue 21, Page(s) 12152–12166

Abstract: DNA replication is a key step in initiating cell proliferation. Loading hexameric complexes of minichromosome maintenance (MCM) helicase onto DNA replication origins during the G1 phase is essential for initiating DNA replication. Here, we examined MCM ... ...

Abstract	DNA replication is a key step in initiating cell proliferation. Loading hexameric complexes of minichromosome maintenance (MCM) helicase onto DNA replication origins during the G1 phase is essential for initiating DNA replication. Here, we examined MCM hexamer states during the cell cycle in human hTERT-RPE1 cells using multicolor immunofluorescence-based, single-cell plot analysis, and biochemical size fractionation. Experiments involving cell-cycle arrest at the G1 phase and release from the arrest revealed that a double MCM hexamer was formed via a single hexamer during G1 progression. A single MCM hexamer was recruited to chromatin in the early G1 phase. Another single hexamer was recruited to form a double hexamer in the late G1 phase. We further examined relationship between the MCM hexamer states and the methylation levels at lysine 20 of histone H4 (H4K20) and found that the double MCM hexamer state was correlated with di/trimethyl-H4K20 (H4K20me2/3). Inhibiting the conversion from monomethyl-H4K20 (H4K20me1) to H4K20me2/3 retained the cells in the single MCM hexamer state. Non-proliferative cells, including confluent cells or Cdk4/6 inhibitor-treated cells, also remained halted in the single MCM hexamer state. We propose that the single MCM hexamer state is a halting step in the determination of cell cycle progression.
MeSH term(s)	Cell Cycle ; DNA/metabolism ; DNA Replication ; HeLa Cells ; Histones/metabolism ; Humans ; Methylation
Chemical Substances	Histones ; DNA (9007-49-2)
Language	English
Publishing date	2021-12-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkab1068
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Zs.A 1067: Show issues

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Article ; Online: Effect of memantine, an anti-Alzheimer’s drug, on rodent microglial cells in vitro

Toru Murakawa-Hirachi / Yoshito Mizoguchi / Masahiro Ohgidani / Yoshinori Haraguchi / Akira Monji

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 11

Abstract: Abstract The pathophysiology of Alzheimer’s disease (AD) is related to neuroinflammatory responses ... Alzheimer’s drug, protects from neuronal death accompanied by suppression of proliferation and activation ...

Abstract	Abstract The pathophysiology of Alzheimer’s disease (AD) is related to neuroinflammatory responses mediated by microglia. Memantine, an antagonist of N-methyl-d-aspartate (NMDA) receptors used as an anti-Alzheimer’s drug, protects from neuronal death accompanied by suppression of proliferation and activation of microglial cells in animal models of AD. However, it remains to be tested whether memantine can directly affect microglial cell function. In this study, we examined whether pretreatment with memantine affects intracellular NO and Ca2+ mobilization using DAF-2 and Fura-2 imaging, respectively, and tested the effects of memantine on phagocytic activity by human β-Amyloid (1–42) phagocytosis assay in rodent microglial cells. Pretreatment with memantine did not affect production of NO or intracellular Ca2+ elevation induced by TNF in rodent microglial cells. Pretreatment with memantine also did not affect the mRNA expression of pro-inflammatory (TNF, IL-1β, IL-6 and CD45) or anti-inflammatory (IL-10, TGF-β and arginase) phenotypes in rodent microglial cells. In addition, pretreatment with memantine did not affect the amount of human β-Amyloid (1–42) phagocytosed by rodent microglial cells. Moreover, we observed that pretreatment with memantine did not affect 11 major proteins, which mainly function in the phagocytosis and degradation of β-Amyloid (1–42), including TREM2, DAP12 and neprilysin in rodent microglial cells. To the best of our knowledge, this is the first report to suggest that memantine does not directly modulate intracellular NO and Ca2+ mobilization or phagocytic activity in rodent microglial cells. Considering the neuroinflammation hypothesis of AD, the results might be important to understand the effect of memantine in the brain.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Palladium-Catalyzed Formylation of Arylzinc Reagents with S-Phenyl Thioformate.

Haraguchi, Ryosuke / Tanazawa, Sho-Go / Tokunaga, Naoya / Fukuzawa, Shin-Ichi

Organic letters

2017 Volume 19, Issue 7, Page(s) 1646–1649

Abstract: The first example of palladium-catalyzed direct formylation of arylzinc reagents using S-phenyl ...

Abstract	The first example of palladium-catalyzed direct formylation of arylzinc reagents using S-phenyl thioformate is reported. The reaction proceeded under mild conditions, allowing high functional group tolerance. In addition, the developed formylation method was used to prepare deuterated and
Language	English
Publishing date	2017-04-07
Publishing country	United States
Document type	Journal Article
ISSN	1523-7052
ISSN (online)	1523-7052
DOI	10.1021/acs.orglett.7b00447
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Article ; Online: S-1 and CPT-11 Plus Ramucirumab (IRIS+Rmab) as Second-Line Chemotherapy for Patients with Oxaliplatin-Refractory Metastatic Colorectal Cancer (mCRC): A Multicenter Phase II Study in Japan (N-DOCC-F-C-1701).

Kobayashi, Kazuma / Morita, Michi / Fukui, Saeko / Ito, Shinichiro / Inoue, Yusuke / Yamaguchi, Izumi / Mine, Yuka / Kosaka, Taiichiro / Kuba, Sayaka / Sakimura, Chika / Yamanouchi, Kosho / Soyama, Akihiko / Ono, Shinichiro / Adachi, Tomohiko / Natsuda, Koji / Okada, Satomi / Tetsuo, Hanako / Ikebe, Ayaka / Yamaguchi, Shun /

The Kurume medical journal

2020 Volume 66, Issue 1, Page(s) 43–47

Abstract: This multicenter phase II N-DOCC-F-C-1701 trial is being planned in order to investigate the efficacy and safety of CPT-11+S-1 +Ramucirumab (IRIS+Rmab), which is anticipated to have a stronger anti-tumor effect than IRIS+Bmab in patients with metastatic ... ...

Abstract	This multicenter phase II N-DOCC-F-C-1701 trial is being planned in order to investigate the efficacy and safety of CPT-11+S-1 +Ramucirumab (IRIS+Rmab), which is anticipated to have a stronger anti-tumor effect than IRIS+Bmab in patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin (L-OHP) containing regimen, in consideration of the result of RAISE, FIRIS and some phase II trials of IRIS+Bevacicizumab (Bmab). The number of patients is set at 38 for the statistical analysis, assuming an expected median PFS of 5.0 months (threshold: 3.0 months). The primary endpoint of the study is the progression free survival (PFS), and the secondary endpoints are the overall response rate (ORR), overall survival (OS), adverse events (AE), quality of life (QOL) and review of nausea and vomiting. This trial is registered in the UMIN Clinical Trials Registry as UMIN000028170. We intend to start conducting the trial in September 1, 2017. If this trial meets the endpoint, IRIS+Rmab might be supported as a new optional standard regimen for mCRC.
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Colorectal Neoplasms/drug therapy ; Drug Resistance, Neoplasm ; Humans ; Irinotecan/therapeutic use ; Oxaliplatin/pharmacology ; Oxaliplatin/therapeutic use ; Quality of Life ; Thiazoles ; Ramucirumab
Chemical Substances	2-cyclohexylidenhydrazo-4-phenyl-thiazole ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Thiazoles ; Oxaliplatin (04ZR38536J) ; Irinotecan (7673326042)
Language	English
Publishing date	2020-05-01
Publishing country	Japan
Document type	Clinical Trial Protocol ; Journal Article
ZDB-ID	603905-4
ISSN	1881-2090 ; 0023-5679
ISSN (online)	1881-2090
ISSN	0023-5679
DOI	10.2739/kurumemedj.MS661007
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Zs.A 704: Show issues

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Article: A Novel Predictive Nomogram for Early Endoscopic Recurrence after Intestinal Resection for Crohn’s Disease

Ikeda, Atsuyo / Miyoshi, Norikatsu / Fujino, Shiki / Iijima, Hideki / Takahashi, Hidekazu / Haraguchi, Naotsugu / Nishimura, Junichi / Hata, Taishi / Matsuda, Chu / Doki, Yuichiro / Mori, Masaki / Mizushima, Tsunekazu

Digestion

2019 Volume 100, Issue 4, Page(s) 269–276

Abstract: Background/Aims: Endoscopic recurrence (ER) after intestinal resection for Crohn’s disease (CD ...

Institution	Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka, Japan Department of Therapeutics for Inflammatory Bowel Diseases, Graduate School of Medicine, Osaka University, Osaka, Japan
Abstract	Background/Aims: Endoscopic recurrence (ER) after intestinal resection for Crohn’s disease (CD) precedes the clinical recurrence, and the severity of ER correlates with the severity of the subsequent clinical recurrence. This study aimed to identify risk factors related to early ER after intestinal resection for CD and to create a prediction model. Methods: The patients who underwent intestinal resection for CD between April 2008 and April 2017 and took endoscopic evaluation between 6 and 12 months after surgery were retrospectively analyzed. Results: A total of 15 out of 52 (29%) patients developed early ER. A univariate analysis demonstrated that early ER was significantly correlated with history of prior intestinal resections for CD (p = 0.005), low preoperative albumin levels (p = 0.035), and excessive perioperative inflammation (i.e., high C-reactive protein levels in both preoperative and postoperative periods; p = 0.034). Based on these clinical factors, a nomogram for predicting early ER was created with the area under the curve 0.808. Conclusion: We developed a novel predictive nomogram for early ER after intestinal resection for CD. This prediction model might assist clinicians in managing patients with CD after an intestinal resection. Additional validation studies are currently being developed.
Keywords	Crohn’s disease ; Endoscopic recurrence ; Prediction model ; Nomogram
Language	English
Publishing date	2019-01-02
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Research Article
ZDB-ID	1712-7
ISSN	1421-9867 ; 0012-2823
ISSN (online)	1421-9867
ISSN	0012-2823
DOI	10.1159/000495981
Database	Karger publisher's database

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Zs.A 572: Show issues

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Article ; Online: High serum concentrations of growth differentiation factor-15 and their association with Crohn’s disease and a low skeletal muscle index

Hiroyuki Yamamoto / Fuminao Takeshima / Masafumi Haraguchi / Yuko Akazawa / Kayoko Matsushima / Moto Kitayama / Kumi Ogihara / Maiko Tabuchi / Keiichi Hashiguchi / Naoyuki Yamaguchi / Hisamitsu Miyaaki / Hisayoshi Kondo / Kazuhiko Nakao

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 8

Abstract: ... physical function. Many sarcopenia biomarkers have been reported. With Crohn’s disease (CD), a low SMI is ... males exhibited a negative correlation between the GDF-15 level and SMI (Pearson’s r = − 0.414; P = 0 ...

Abstract	Abstract Sarcopenia comprises a low skeletal muscle index (SMI) and low muscle strength (MS) or low physical function. Many sarcopenia biomarkers have been reported. With Crohn’s disease (CD), a low SMI is predictive of intestinal complications. Therefore, many CD studies have reported that sarcopenia is defined by SMI alone. This study investigated the sarcopenia frequency by assessing the SMI and MS of Japanese patients with CD and biomarkers predicting a low SMI. We evaluated the SMI using a bioelectrical impedance analysis, handgrip strength, and C-reactive protein, albumin, interleukin-6, tumor necrosis factor-α, growth differentiation factor (GDF)-8, and GDF-15 levels as biomarker candidates for 78 CD patients at our hospital. Sarcopenia and a low SMI were observed in 7.7% and 42.3% of the patients, respectively. There was a significant difference in the GDF-15 levels of the low SMI group and normal group according to the multivariate analysis (P = 0.028; odds ratio [OR], 1.001; 95% confidence interval [CI] 1.000–1.002). When evaluated by sex, males exhibited a negative correlation between the GDF-15 level and SMI (Pearson’s r = − 0.414; P = 0.0031), and the multivariate analysis indicated a significant difference in the GDF-15 levels (P = 0.011; OR, 1.001; 95% CI 1.000–1.002). GDF-15 levels may indicate a low SMI with CD.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Human Intervention in the Earth’s Climate

Masahiko Haraguchi / Rongkun Liu / Jasdeep Randhawa / Susanne Salz / Stefan Schäfer / Mudit Sharma / Susan Chan Shifflett / Akiko Suzuki / Ying Yuan

The Governance of Geoengineering in 2025+

2015

Publishing country	de
Document type	Book ; Online
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Article: Innate Myeloid Cell Subset-Specific Gene Expression Patterns in the Human Colon are Altered in Crohn’s Disease Patients

Sekido, Yuki / Yasumizu, Yoshiaki / Nishimura, Junichi / Kayama, Hisako / Matsuno, Hiroshi / Ogino, Takayuki / Miyoshi, Norikatsu / Takahashi, Hidekazu / Haraguchi, Naotsugu / Hata, Taishi / Matsuda, Chu / Doki, Yuichiro / Mori, Masaki / Takeda, Kiyoshi / Ohkura, Naganari / Sakaguchi, Shimon / Mizushima, Tsunekazu

Digestion

2018 Volume 99, Issue 3, Page(s) 194–204

Abstract: ... in the pathogenesis of Crohn’s disease (CD). However, the detailed mechanisms by which each innate myeloid subset ... the inflamed colon sites from patients with Crohn’s disease (CDi). Methods: We performed RNA-sequencing ...

Institution	Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Japan Laboratory of Mucosal Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo, Japan Department of Therapeutics for Inflammatory Bowel Diseases, Graduate School of Medicine, Osaka University, Suita, Japan
Abstract	Background/Aims: There is a heterogeneous subset innate myeloid cells, such as macrophages and dendritic cells, in the human intestinal lamina propria. Several studies have demonstrated that these cells contribute to the maintenance of gut homeostasis through the induction of inflammatory responses and tolerance via cell type-specific mechanisms; whereas, disrupted innate immune responses are implicated in the pathogenesis of Crohn’s disease (CD). However, the detailed mechanisms by which each innate myeloid subset regulates gut homeostasis and inflammation largely remain unknown. We aimed to clarify the comprehensive gene expression profiles of innate myeloid cell subsets in the lamina propria from normal human colons (NC) and the inflamed colon sites from patients with Crohn’s disease (CDi). Methods: We performed RNA-sequencing analysis and precise bioinformatics analysis on 3 innate myeloid cell subsets, CD14CD11c, CD14CD11c, and CD14CD11cCD163low cells from NC and CDi. Results: Transcriptional analysis of the 3 subsets from the NC showed distinct gene expression patterns and gene ontology (GO) enrichment analysis revealed the associated innate myeloid subset-specific biological process (BP) terms. In addition, changes in gene expression patterns were observed in innate myeloid subsets from CDi. Furthermore, the core GO-BP terms for the genes upregulated in the innate myeloid cells from CDi were distinct from those found in NC. Conclusion: Our data identified the innate myeloid cell subset-specific transcriptomes and the associated enriched GO-BP terms in the NC and found these patterns were altered in CDi.
Keywords	Crohn’s disease ; Human colon ; Inflammatory bowel diseases ; Innate myeloid cell ; RNA-seq analysis
Language	English
Publishing date	2018-10-19
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Original Paper
ZDB-ID	1712-7
ISSN	1421-9867 ; 0012-2823
ISSN (online)	1421-9867
ISSN	0012-2823
DOI	10.1159/000490890
Database	Karger publisher's database

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