Details of the Researcher

PHOTO

Hidekazu Shirota
Section
Graduate School of Medicine
Job title
Associate Professor
Degree

  • 博士（医学）（東北大学）

Research History 5

  • 2017/08 - Present
    東北大学医学系研究科　地域がん医療推進センター　准教授

  • 2012/06 - 2017/07
    東北大学医学系研究科　地域がん医療推進センター　講師

  • 2008/04 - 2012/05
    米国国立衛生研究所　国立癌研究所　スタッフサイエンティスト

  • 2007/04 - 2008/03
    東北大学医学系研究科　感染症・呼吸器内科　助教

  • 2002/04 - 2007/03
    米国食品医薬品庁　生物製剤評価研究センター　博士研究員

Education 2

  • 東北大学大学院　医学系研究科　医科学博士課程

    1998/04 - 2002/03

  • Fukushima Medical University　School of Medicine

    1990/04 - 1996/03

Professional Memberships 6

  • JAPANESE SOCIETY OF ALLERGOLOGY

  • THE JAPANESE CANCER ASSOCIATION

  • JAPAN SOCIETY OF CLINICAL ONCOLOGY

  • THE JAPANESE SOCIETY FOR IMMUNOLOGY

  • JSMO

  • THE JAPANESE SOCIETY OF INTERNAL MEDICINE

︎Show all ︎Show first 5

Research Interests 1

  • Tumor immunology

Research Areas 1

  • Life sciences / Immunology / Tumor immunology

Awards 1

  1. Technology Transfer Award

    2011　National Cancer Institute, NIH

Papers 97

  1. Impact of genetic mutations on prognosis and chemotherapy efficacy in advanced appendiceal carcinoma: insights from the nationwide Japanese comprehensive genomic profiling test database.

    Sakura Hiraide Taniguchi, Masanobu Takahashi, Shih-Wei Chiu, Keigo Komine, Shonosuke Wakayama, Ryunosuke Numakura, Yuya Yoshida, Yuki Kasahara, Kota Ouchi, Hiroo Imai, Ken Saijo, Hidekazu Shirota, Chikashi Ishioka

    International journal of clinical oncology　2025/02/28

    DOI： 10.1007/s10147-025-02724-2 　

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    BACKGROUND: Appendiceal carcinoma (AC) is a rare malignancy and has distinct genomic features, but their impact on prognosis and chemotherapy efficacy requires further investigation. METHODS: This retrospective study analyzed patients with advanced AC from the Japanese nationwide comprehensive genomic profiling test database, the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, focusing on genetic alterations and their associations with clinical outcomes. RESULTS: Of the 314 patients, the histological types Queryincluded adenocarcinoma (Ad) (51.9%), mucinous adenocarcinoma (MAd) (30.3%), goblet cell adenocarcinoma (12.4%), and signet-ring cell adenocarcinoma (5.4%). The most common mutations were KRAS (52.5%), TP53 (49.4%), SMAD4 (18.8%), and GNAS (17.2%). KRAS mutations were most frequent in MAd (68.4%) and Ad (58.9%), whereas TP53 mutations were mostly prevalent in Ad (62.6%). We classified patients into molecular subtypes based on the presence of mutations and analyzed differences in overall survival (OS) by molecular subtype. Patients with TP53-mutant (mut) dominant tumors (all TP53-mut) and KRAS-mut focused tumors (TP53-wild-type (wt)/GNAS-wt/KRAS-mut/any SMAD4) showed a poorer median OS compared with those with GNAS-mut focused tumors (TP53-wt/GNAS-mut/any KRAS /any SMAD4) (median 47.4 and 37.5 months vs. not reached; p = 0.01 and p = 0.01, respectively). TP53 mutation was associated with poor time to treatment failure and OS with the oxaliplatin-based regimen for first-line chemotherapy. CONCLUSIONS: This study suggested that the genetic mutations influenced the prognosis and chemotherapy efficacy in AC.

  2. Pretreatment neutrophil-lymphocyte ratio as a prognostic factor in recurrent/metastatic head and neck cancer treated with pembrolizumab. International-journal

    Yuki Kasahara, Ken Saijo, Reio Ueta, Ryunosuke Numakura, Keiju Sasaki, Yuya Yoshida, Sakura Taniguchi, Kota Ouchi, Keigo Komine, Hiroo Imai, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Scientific reports　14　(1)　28255-28255　2024/11/16

    DOI： 10.1038/s41598-024-79130-7 　

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    Pembrolizumab-containing regimens are the standard first-line treatment for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC). The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-albumin ratio (CAR) have been reported to be important prognostic factors in a variety of carcinomas, but none have been investigated in combination with pembrolizumab and chemotherapy or in first-line treatment. Seventy-four patients with R/M HNSCC received pembrolizumab-containing regimens at Tohoku University Hospital, Sendai, Japan, from April 2020 to March 2023. Patient characteristics, tumor response, overall survival (OS), progression-free survival (PFS), and laboratory findings were reviewed. Associations between NLR, CAR, and survival outcomes were analyzed. The 1-year OS and 1-year PFS rates were 60.4% and 18.1%, respectively. The disease control rate was 66.2%. In multivariate analysis, low NLR (< 5) was significantly associated with better OS and PFS. NLR may be a predictive factor for OS and PFS in patients with R/M HNSCC treated with a pembrolizumab-containing regimen.

  3. Specific cancer types and prognosis in patients with variations in the <scp>KEAP1</scp>‐<scp>NRF2</scp> system: A retrospective cohort study Peer-reviewed

    Tomoyuki Iwasaki, Hidekazu Shirota, Keiju Sasaki, Kota Ouchi, Yuki Nakayama, Hiroyuki Oshikiri, Akihito Otsuki, Takafumi Suzuki, Masayuki Yamamoto, Chikashi Ishioka

    Cancer Science　2024/09/26

    DOI： 10.1111/cas.16355 　

    ISSN： 1347-9032 1349-7006

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    <jats:title>Abstract</jats:title><jats:p>The KEAP1–NRF2 system induces the expression of antioxidant genes in response to various types of oxidative stress. Some cancer cells activate this system, which increases their malignancy through genetic mutations. We performed a retrospective cohort study using the C‐CAT database, which contains the gene‐panel sequence data from 60,056 cases of diagnosed solid tumors. We analyzed somatic mutations in <jats:italic>NRF2</jats:italic> and <jats:italic>KEAP1</jats:italic> genes and their associations with clinical outcomes. Variants in the <jats:italic>NRF2</jats:italic> gene were clustered in exon 2, which encodes the DLG and ETGE motifs essential for KEAP1 interaction. The <jats:italic>NRF2</jats:italic> variants were frequently observed in esophageal and lung squamous cell carcinoma with frequencies of 35.9% and 19.6%, respectively. Among these mutations, the <jats:italic>NRF2</jats:italic> variants in the ETGE motif were indicators of a worse prognosis. <jats:italic>KEAP1</jats:italic> variants were found in 2.5% of all cases. The variants were frequent in lung cancer and showed a worse prognosis in lung and other types of adenocarcinomas. We then conducted gene expression analysis using TCGA data. While cancers with DLG and ETGE variants were similar in terms of gene expression profiles, there were significant differences between cancers with <jats:italic>KEAP1</jats:italic> and <jats:italic>NRF2</jats:italic> variants. Our results indicate that genetic alteration of the KEAP1–NRF2 pathway is a major factor in patient prognosis for each cancer type and its genetic variant. Variants in <jats:italic>NRF2</jats:italic> and <jats:italic>KEAP1</jats:italic> genes can characterize the biological basis of each cancer type and are involved in carcinogenesis, resistance to therapy, and other biological differences.</jats:p>

  4. Correlation between Efficacy and Cardiovascular Adverse Events in Patients with Advanced Solid Cancer Who Received VEGF Pathway Inhibitors: Hypertension within the First Eight Weeks is Associated with Favorable Outcomes of Patients Treated with VEGF Pathway Inhibitors.

    Yuya Yoshida, Masanobu Takahashi, Keigo Komine, Sakura Taniguchi, Hideharu Yamada, Keiju Sasaki, Sho Umegaki, Yoshifumi Kawamura, Yuki Kasahara, Kota Ouchi, Hiroo Imai, Ken Saijo, Hidekazu Shirota, Noriko Takenaga, Chikashi Ishioka

    Internal medicine (Tokyo, Japan)　2024/06/13

    DOI： 10.2169/internalmedicine.3373-23 　

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    Objective Many vascular endothelial growth factor (VEGF) pathway inhibitors are used in the treatment of patients with various advanced cancers; however, treatments induce cardiovascular adverse events (CVAEs), such as hypertension, heart failure, arrhythmia, arterial or venous embolism, and hemorrhage. Some studies have suggested a correlation between efficacy and CVAEs; however, further evidence is required. This study evaluated real-world data concerning the frequency and degree of CVAEs and possible associations between CVAEs and efficacy in such patients. Methods and Patients We analyzed CVAEs observed in 294 patients with advanced cancer who were treated with ramucirumab, regorafenib, pazopanib, sunitinib, or sorafenib. Results CVAEs of any grade and proteinuria within 8 weeks after the initiation of VEGF pathway inhibitors (early) or during the treatment period (total period) were observed in 72%-85% and 77%-92% of the patients, respectively. The progression-free survival (PFS) of patients with a CVAE of grade ≥1 in the early period was favorable compared with the PFS of those who had no CVAE (median, 4.9 vs. 3.5 months, P = 0.016, log-rank test). Furthermore, the PFS of patients with a CVAE grade ≥3 in the early period was favorable compared to that of those with CVAEs of grades 0-2. Taken together, a higher degree of CVAE was correlated with favorable patient outcomes. Conclusion This study revealed the frequency and degree of CVAEs in patients with solid cancers who received VEGF pathway inhibitors in a real-world setting and added evidence regarding the correlation between CVAEs and efficacy of VEGF pathway inhibitors.

  5. Genome-wide DNA methylation status is a predictor of the efficacy of anti-EGFR antibodies in the second-line treatment of metastatic colorectal cancer: Translational research of the EPIC trial. International-journal

    Kota Ouchi, Shin Takahashi, Keiju Sasaki, Yuya Yoshida, Sakura Taniguchi, Yuki Kasahara, Keigo Komine, Hiroo Imai, Ken Saijo, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    International journal of colorectal disease　39　(1)　89-89　2024/06/11

    DOI： 10.1007/s00384-024-04659-y 　

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    PURPOSE: The genome-wide DNA methylation status (GWMS) predicts of therapeutic response to anti-epidermal growth factor receptor (EGFR) antibodies in treating metastatic colorectal cancer. We verified the significance of GWMS as a predictive factor for the efficacy of anti-EGFR antibodies in the second-line treatment of metastatic colorectal cancer. METHODS: Clinical data were obtained from a prospective trial database, and a genome-wide DNA methylation analysis was performed. GWMS was classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). The patients were divided into subgroups according to the treatment arm (cetuximab plus irinotecan or irinotecan alone) and GWMS, and the clinical outcomes were compared between the subgroups. RESULTS: Of the 112 patients, 58 (51.8%) were in the cetuximab plus irinotecan arm, and 54 (48.2%) were in the irinotecan arm; 47 (42.0%) were in the HMCC, and 65 (58.0%) were in the LMCC group regarding GWMS. Compared with the LMCC group, the progression-free survival (PFS) was significantly shortened in the HMCC group in the cetuximab plus irinotecan arm (median 1.4 vs. 4.1 months, p = 0.001, hazard ratio = 2.56), whereas no significant differences were observed in the irinotecan arm. A multivariate analysis showed that GWMS was an independent predictor of PFS and overall survival (OS) in the cetuximab plus irinotecan arm (p = 0.002, p = 0.005, respectively), whereas GWMS did not contribute to either PFS or OS in the irinotecan arm. CONCLUSIONS: GWMS was a predictive factor for the efficacy of anti-EGFR antibodies in the second-line treatment of metastatic colorectal cancer.

  6. Chylous Ascites Associated with Advanced Pancreatic Cancer That Improved with Appropriate Treatment: A Case Report. International-journal

    Hiroo Imai, Ken Saijo, Noriko Takenaga, Keigo Komine, Kota Ouchi, Yuki Kasahara, Shiori Ishikawa, Keiju Sasaki, Yuya Yoshida, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Current oncology (Toronto, Ont.)　31　(3)　1477-1482　2024/03/12

    DOI： 10.3390/curroncol31030112 　

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    Chylous ascites is a rare form of ascites with high triglyceride content arising from the thoracoabdominal lymph nodes in the peritoneal cavity due to various benign or malignant etiologies, including pancreatic cancer. During cancer chemotherapy, the accumulation of ascites can lead to the deterioration of the patient's general condition, making chemotherapy administration difficult, and resulting in a poor prognosis. We encountered a rare case of chylous ascites complicated by advanced pancreatic cancer. The patient presented with a discrepancy between the shrinkage of the pancreatic cancer and the accumulation of ascites. Therefore, we were able to promptly diagnose chylous ascites by performing biochemical tests. The patient was treated with octreotide, reportedly effective in treating chylous ascites, which rapidly improved the chylous ascites and general condition of the patient, allowing the patient to continue chemotherapy for pancreatic cancer. Therefore, physicians should consider the possibility of chylous ascites when clinically unexplained ascites are observed in patients with advanced cancer. The investigation and treatment of chylous ascites should be initiated as soon as possible.

  7. FOLFIRI Chemotherapy for Patients With Metastatic Urachal Carcinoma. International-journal

    Sakura Hiraide Taniguchi, Keigo Komine, Noriko Takenaga, Yuya Yoshida, Keiju Sasaki, Yoshifumi Kawamura, Yuki Kasahara, Kota Ouchi, Hiroo Imai, Ken Saijo, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Anticancer research　43　(12)　5699-5704　2023/12

    DOI： 10.21873/anticanres.16775 　

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    BACKGROUND/AIM: Urachal carcinoma is a rare cancer, with limited evidence regarding systemic chemotherapy for metastatic urachal carcinoma. This study aimed to evaluate the efficacy and safety of a combination therapy of 5-fluorouracil and irinotecan (FOLFIRI) in patients with metastatic urachal carcinoma. PATIENTS AND METHODS: Patients with metastatic urachal carcinoma treated with FOLFIRI between March 2008 and April 2023 at the Department of Medical Oncology, Tohoku University Hospital, were retrospectively analyzed using medical records. RESULTS: Six patients with urachal carcinoma received FOLFIRI. The histological type was adenocarcinoma in all patients. The metastatic or recurrent sites were the peritoneum, lungs, lymph nodes, and local relapse sites. Three patients received FOLFIRI as first-line chemotherapy, and the other three received FOLFIRI as second-line chemotherapy. Two patients had only non-measurable lesions as the targets of tumor response. The best response was the stable disease or non-complete response/non-progressive disease in four patients, with a disease control rate of 67%. The median progression-free survival was 7.5 months. In two patients with ascites only as the site of metastasis, the amount of ascites and serum tumor marker levels decreased after FOLFIRI was initiated. Grade 3/4 toxicities included grade 3 neutropenia in one patient and grade 3 diarrhea in one patient. CONCLUSION: FOLFIRI has modest efficacy and good tolerability for the treatment of metastatic urachal carcinoma.

  8. Comparison of efficacy and safety between carboplatin-etoposide and cisplatin-etoposide combination therapy in patients with advanced neuroendocrine carcinoma, retrospective study. International-journal

    Hiroo Imai, Ken Saijo, Yoshifumi Kawamura, Shuto Kodera, Keigo Komine, Tomoyuki Iwasaki, Noriko Takenaga, Yuki Kasahara, Kota Ouchi, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Oncology　2023/10/30

    DOI： 10.1159/000534747 　

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    INTRODUCTION: Neuroendocrine carcinoma (NEC) is characterized by a poor prognosis and is generally treated with platinum and etoposide combination therapy as first-line chemotherapy. However, it remains uncertain whether carboplatin and etoposide combination therapy (CE) and cisplatin and etoposide combination therapy (PE) have comparable treatment efficacy. In this retrospective analysis, we compared the efficacy and safety of CE and PE in patients with NEC. METHODS: We retrospectively reviewed the patient's clinical record from 2005 to 2022 at the Department of Medical Oncology, Tohoku University Hospital. Patients who received either CE or PE were included in the study. Statistical analyses were performed using JMP Pro 16.0 (SAS Institute Inc., Cary, N.C., USA). RESULTS: A total of 104 patients were enrolled, with 73 patients assigned to the CE group and 31 patients assigned to the PE group. Statistically, the response rate, progression-free survival (PFS) time and overall survival (OS) time were 42.6%, 5.1 months (95%CI: 3.5-6.3) and 13.6 months (95%CI: 8.9-17.4), respectively, in the CE groups and 44.4%, 5.6 months (95%CI: 3.1-7.0) and 12.5 months (95%CI: 11.2-14.6), respectively, in the PE groups. There was no significant difference in treatment efficacy between the CE and the PE groups. However, the number of patients with elevated creatinine (3.35 mg/dl and 3.88 mg/dl in two patients, respectively) was significantly higher in the PE group than in the CE group. CONCLUSION: The efficacy of CE and PE in patients with NEC is comparable. However, the incidence of renal dysfunction was found to be significantly higher in the PE group than in the CE group.

  9. Antibiotics May Interfere with Nivolumab Efficacy in Patients with Head and Neck Squamous Cell Carcinoma

    Reio Ueta, Hiroo Imai, Ken Saijo, Yoshifumi Kawamura, Shuto Kodera, Keigo Komine, Kota Ouchi, Yuki Kasahara, Sakura Taniguchi, Yuya Yoshida, Keiju Sasaki, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Oncology　1-8　2023/09/14

    Publisher: S. Karger AG

    DOI： 10.1159/000533860 　

    ISSN： 0030-2414

    eISSN： 1423-0232

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    Introduction: Patients with the head and neck squamous cell carcinoma (SCC) are often treated with immune checkpoint inhibitors (ICIs). Recently, antibiotic intake was reported to lower the efficacy of ICIs in patients with several types of cancers. However, it is unclear if antibiotics affect the efficacy of ICIs in patients with head and neck SCC. We retrospectively assessed the influence of antibiotics on the treatment efficacy of nivolumab, an ICI, in patients with head and neck SCC. Methods: We reviewed the medical records of patients with head and neck SCC treated with nivolumab at the Department of Medical Oncology, Tohoku University Hospital, between 2017 and 2021. Patients who received oral or intravenous antibiotics from a month before the day of nivolumab initiation to the day of the first imaging evaluation of ICI efficacy were assigned to the antibiotic-treated group. The remaining patients were assigned to the antibiotic-untreated group. The response rate (RR), progression-free survival (PFS), and overall survival time (OS) of both groups were compared. Results: Forty-five patients were assigned to the antibiotic-treated group and 19 to the antibiotic-untreated group. The RR, median PFS, and median OS of the antibiotic-treated group were 23.7%, 3.2 months (95% confidential interval [CI]: 2.0–4.1), and 8.4 months (95% CI: 5.3–15.1) and those of the antibiotic-untreated group were 42.1%, 5.8 months (95% CI: 2.3–16.7), and 18.4 months (95% CI: 6.2–23.1), respectively. The PFS of the antibiotic-untreated group was significantly longer than that of the antibiotic-treated group. Conclusion: Our findings indicate that antibiotic treatment significantly shortens the PFS with nivolumab therapy in patients with head and neck SCC.

  10. Distinct role of CD8 cells and CD4 cells in antitumor immunity triggered by cell apoptosis using a Herpes simplex virus thymidine kinase/ganciclovir system. International-journal

    Sho Umegaki, Hidekazu Shirota, Yuki Kasahara, Tomoyuki Iwasaki, Chikashi Ishioka

    Cancer science　114　(8)　3076-3086　2023/08

    DOI： 10.1111/cas.15843 　

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    Immune cells can recognize tumor-associated antigens released from dead tumor cells, which elicit immune responses, potentially resulting in tumor regression. Tumor cell death induced by chemotherapy has also been reported to activate immunity. However, various studies have reported drug-induced immunosuppression or suppression of inflammation by apoptotic cells. Thus, this study aimed to investigate whether apoptotic tumor cells trigger antitumor immunity independent of anticancer treatment. Local immune responses were evaluated after direct induction of tumor cell apoptosis using a Herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system. The inflammatory response was significantly altered at the tumor site after apoptosis induction. The expression of cytokines and molecules that activate and suppress inflammation simultaneously increased. The HSV-tk/GCV-induced tumor cell apoptosis resulted in tumor growth suppression and promoted T lymphocyte infiltration into tumors. Therefore, the role of T cells after inducing tumor cell death was explored. CD8 T cell depletion abrogated the antitumor efficacy of apoptosis induction, indicating that tumor regression was mainly dependent on CD8 T cells. Furthermore, CD4 T cell depletion inhibited tumor growth, suggesting the potential role of CD4 T cells in suppressive tumor immunity. Tumor tissues were evaluated after tumor cell apoptosis and CD4 T cell depletion to elucidate this immunological mechanism. Foxp3 and CTLA4, regulatory T-cell markers, decreased. Furthermore, arginase 1, an immune-suppressive mediator induced by myeloid cells, was significantly downregulated. These findings indicate that tumors accelerate CD8 T cell-dependent antitumor immunity and CD4 T cell-mediated suppressive immunity. These findings could be a therapeutic target for immunotherapy in combination with cytotoxic chemotherapy.

  11. TP53 Gain-of-Function Mutation is a Poor Prognostic Factor in High-Methylated Metastatic Colorectal Cancer. International-journal

    Shonosuke Wakayama, Kota Ouchi, Shin Takahashi, Yasuhide Yamada, Yoshito Komatsu, Ken Shimada, Tatsuro Yamaguchi, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Clinical colorectal cancer　2023/06/07

    DOI： 10.1016/j.clcc.2023.06.001 　

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    BACKGROUND: Neither TP53 mutation nor DNA methylation status has been established as a biomarker alone of metastatic colorectal cancer. We analyzed the association between TP53 mutation functional subtypes and genome-wide DNA methylation status (GWMS) as combined prognostic markers. METHODS: Patient clinical data were obtained from the TRICOLORE study, a randomized phase III trial. The TP53 mutations were classified into wild-type, gain-of-function (GOF) mutations, and non-gain-of-function (non-GOF) mutations. GWMS of the tumor tissues classified them into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). Overall survival (OS) was compared based on these subgroups. RESULTS: Of the 209 patients, 60 (28.7%) were HMCC and 149 (71.3%) were LMCC, 35 (16.7%) were TP53 wild-type and 174 (83.3%) were TP53 mutants including 79 (45.4%) GOF mutations and 95 (54.6%) non-GOF mutations. The OS of the HMCC group was shorter than that of the LMCC group (median 25.3 vs. 40.3 months, P < .001, hazard ratio 1.87) in the total cohort. The combined subgroup analyses of GWMS and TP53 mutation subtypes showed that the HMCC/GOF group had significantly shorter OS than the HMCC/non-GOF group, the LMCC/GOF group, and the LMCC/non-GOF group (median 17.7; 35.3, 40.3, and 41.2 months, P = .007, P < .001, and P < .001, respectively), regardless of the primary tumor location. By the multivariate analysis, only HMCC (P = .009) was a poor prognostic factor in the GOF mutation group. CONCLUSIONS: TP53 GOF with HMCC is a newly identified poorest prognostic molecular subset in metastatic colorectal cancer.

  12. Management of patients with presumed germline pathogenic variant from tumor-only genomic sequencing: A retrospective analysis at a single facility. International-journal

    Maako Kawamura, Hidekazu Shirota, Tetsuya Niihori, Keigo Komine, Masanobu Takahashi, Shin Takahashi, Eisaku Miyauchi, Hidetaka Niizuma, Atsuo Kikuchi, Hiroshi Tada, Muneaki Shimada, Naoki Kawamorita, Masayuki Kanamori, Ikuko Sugiyama, Mari Tsubata, Hitotshi Ichikawa, Jun Yasuda, Toru Furukawa, Yoko Aoki, Chikashi Ishioka

    Journal of human genetics　68　(6)　399-408　2023/02/20

    DOI： 10.1038/s10038-023-01133-5 　

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    Cancer treatment is increasingly evolving toward personalized medicine, which sequences numerous cancer-related genes and identifies therapeutic targets. On the other hand, patients with germline pathogenic variants (GPV) have been identified as secondary findings (SF) and oncologists have been urged to handle them. All SF disclosure considerations for patients are addressed and decided at the molecular tumor boards (MTB) in the facility. In this study, we retrospectively summarized the results of all cases in which comprehensive genomic profiling (CGP) test was conducted at our hospital, and discussed the possibility of presumed germline pathogenic variants (PGPV) at MTB. MTB recommended confirmatory testing for 64 patients. Informed consent was obtained from attending physicians for 53 of them, 30 patients requested testing, and 17 patients tested positive for a confirmatory test. Together with already known variants, 4.5 % of the total confirmed in this cohort. Variants verified in this study were BRCA1 (n = 12), BRCA2 (n = 6), MSH2 (n = 2), MSH6 (n = 2), WT1 (n = 2), TP53, MEN1, CHEK2, MLH1, TSC2, PTEN, RB1, and SMARCB1. There was no difference in the tumor's VAF between confirmed positive and negative cases for variants determined as PGPV by MTB. Current results demonstrate the actual number of cases until confirmatory germline test for patients with PGPV from tumor-only CGP test through the discussion at the MTB. The practical results at this single facility will serve as a guide for the management of the selection and distribution of SF in the genome analysis.

  13. Depth of response may predict clinical outcome in patients with recurrent/metastatic head and neck cancer treated with pembrolizumab-containing regimens. International-journal

    Ken Saijo, Hiroo Imai, Kota Ouchi, Keiju Sasaki, Yuya Yoshida, Yoshifumi Kawamura, Sakura Taniguchi, Yuki Kasahara, Keigo Komine, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Frontiers in oncology　13　1230731-1230731　2023

    DOI： 10.3389/fonc.2023.1230731 　

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    BACKGROUND: Pembrolizumab-containing regimens are standards of care for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). The depth of response (DpR) predicts the survival of patients with several types of solid cancers; however, its association with the survival outcomes of patients with R/M HNSCC treated with pembrolizumab-containing regimens remains unclear. METHODS: This study included 66 patients with R/M HNSCC who received a pemblolizumab-containing regimen as a first-line therapy at Tohoku University Hospital, Sendai, Japan. The patients' characteristics, combined positive score, baseline tumor size, tumor response, DpR, overall survival (OS), progression-free survival (PFS), PFS2, and adverse events were reviewed. The associations between DpR and survival outcomes were analyzed. RESULTS: The 1 year-OS and 1 year-PFS rates of pembrolizumab-containing regimens were 69.4% and 24.4%, respectively. The response rate was 28.8%. The mean and median values of tumor change from baseline were 5.1% and -9.0%. In the correlation analysis, a significant negative correlation was observed between tumor change rate from baseline and survival outcomes (OS: r= -0.41, p=0.0017; PFS: r=-0.49, p<0.001). In the multivariate analysis, DpR with tumor change of ≤-45 was associated with better OS and PFS. CONCLUSION: DpR induced by pembrolizumab-containing regimens may be a predictive factor for OS and PFS in patients with R/M HNSCC.

  14. Clinical decisions by the molecular tumor board on comprehensive genomic profiling tests in Japan: A retrospective observational study. International-journal

    Hidekazu Shirota, Keigo Komine, Masanobu Takahashi, Shin Takahashi, Eisaku Miyauchi, Hidetaka Niizuma, Hiroshi Tada, Muneaki Shimada, Tetsuya Niihori, Yoko Aoki, Ikuko Sugiyama, Maako Kawamura, Jun Yasuda, Shuhei Suzuki, Takeshi Iwaya, Motonobu Saito, Tsuyoshi Saito, Hiroyuki Shibata, Toru Furukawa, Chikashi Ishioka

    Cancer medicine　12　(5)　6170-6181　2022/10/17

    DOI： 10.1002/cam4.5349 　

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    BACKGROUND: A paradigm shift has occurred in cancer chemotherapy from tumor-specific treatment with cytotoxic agents to personalized medicine with molecular-targeted drugs. Thus, it is essential to identify genomic alterations and molecular features to recommend effective targeted molecular medicines regardless of the tumor site. Nevertheless, it takes considerable expertise to identify treatment targets from primary-sequencing data in order to provide drug recommendations. The Molecular Tumor Board (MTB) denotes a platform that integrates clinical and molecular features for clinical decisions. METHODS: This study retrospectively analyses all the cases of discussion and decision at the MTB in Tohoku University Hospital and summarizes genetic alterations and treatment recommendations. RESULTS: The MTB discussed 1003 comprehensive genomic profiling (CGP) tests conducted in patients with solid cancer, and the resulting rate of assessing treatment recommendations was approximately 19%. Among hundreds of genes in the CGP test, only 30 genetic alterations or biomarkers were used to make treatment recommendations. The leading biomarkers that led to treatment recommendations were tumor mutational burden-high (TMB-H) (n = 32), ERBB2 amplification (n = 24), BRAF V600E (n = 16), and BRCA1/2 alterations (n = 32). Thyroid cancer accounted for most cancer cases for which treatment recommendation was provided (81.3%), followed by non-small cell lung cancer (42.4%) and urologic cancer (31.3%). The number of tests performed for gastrointestinal cancers was high (n = 359); however, the treatment recommendations for the same were below average (13%). CONCLUSION: The results of this study may be used to simplify treatment recommendations from the CGP reports and help select patients for testing, thereby increasing the accuracy of personalized medicine.

  15. BRAF and MEK Inhibitor Treatment for Metastatic Undifferentiated Sarcoma of the Spermatic Cord with BRAF V600E Mutation

    Ken Saijo, Hiroo Imai, Hiromichi Katayama, Fumiyoshi Fujishima, Kenichi Nakamura, Yuki Kasahara, Kota Ouchi, Keigo Komine, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Case Reports in Oncology　762-769　2022/08/30

    Publisher: S. Karger AG

    DOI： 10.1159/000526018 　

    eISSN： 1662-6575

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    An 18-year-old Japanese man was diagnosed with an undifferentiated sarcoma of the spermatic cord, with multiple distant metastases to the lungs and bones. The patient received doxorubicin-based standard chemotherapy. Although the chemotherapy was effective, it induced severe adverse events, which led to treatment discontinuation. A comprehensive genomic profiling test using resected tumor tissue revealed the &lt;i&gt;BRAF&lt;/i&gt; V600E mutation. Based on the result, the patient received combination therapy with dabrafenib and trametinib. The combination therapy achieved a good response with few adverse events. However, 6.5 months later, pleural metastases and meningeal dissemination had emerged. A liquid comprehensive genomic profiling test was performed after the progression to identify the resistance mechanism, which resulted in the detection of no actionable gene alterations other than &lt;i&gt;BRAF&lt;/i&gt; V600E. This report shows that the &lt;i&gt;BRAF&lt;/i&gt; V600E mutation may be a promising therapeutic target and that resistance to the targeted therapy could also occur in soft tissue sarcoma. The significance of &lt;i&gt;BRAF&lt;/i&gt; mutations across different types of cancer should be validated, and it is necessary to apply targeted therapies and develop methods to overcome resistance based on the optimal use of comprehensive genomic profiling tests.

  16. Cisplatin Plus Capecitabine After Adjuvant S-1 in Metastatic Gastric Cancer: A Phase II T-CORE1102 Trial. International-journal

    Takashi Yoshioka, Masanobu Takahashi, Yasuhiro Sakamoto, Akira Okita, Tadahisa Fukui, Yasuko Murakawa, Yoshiaki Shindo, Hiroo Imai, Hisatsugu Ohori, Hidekazu Shirota, Natsuko Chiba, Yuriko Ito Sasahara, Takashi Nomura, Norimasa Fukushima, Takuhiro Yamaguchi, Hideki Shimodaira, Chikashi Ishioka

    Anticancer research　42　(4)　2009-2015　2022/04

    DOI： 10.21873/anticanres.15680 　

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    BACKGROUND/AIM: This phase II study assessed the efficacy of capecitabine plus cisplatin in patients with advanced gastric cancer refractory to adjuvant S-1. PATIENTS AND METHODS: This single-arm, open-label, multicenter, phase II study was conducted by Tohoku Clinical Oncology Research and Education Society (T-CORE) in Japan. Patients aged ≥20 years with advanced HER2-negative gastric cancer that was refractory to S-1 were enrolled. Patients received 80 mg/m2 cisplatin on day 1 intravenously and 1,000 mg/m2 capecitabine twice daily from day 1 to day 14, in 3-week cycles. The primary endpoint was progression-free survival (PFS). The threshold overall response rate (ORR) was estimated to be 15%. The secondary endpoints were overall survival (OS), time to treatment failure, ORR, and toxicities. RESULTS: In total, 21 patients were enrolled from seven hospitals. The median patient age was 63 years. Nineteen patients received the protocol treatment. Median PFS was 3.7 months [90% confidence interval (CI)=2.7-5.6 months], which did not reach the predefined threshold of 4.0 months. ORR was 5.9% (95%CI=0.0-17.1%). Median OS was 11.9 months (95% CI 6.3-19.4 months). Febrile neutropenia was observed in 5.3% of patients. The most frequently observed grade 3 non-hematologic toxicities were nausea (15.8%) and hyponatremia (15.8%). CONCLUSION: The addition of a fluoropyrimidine to a platinum agent after adjuvant therapy is not suitable for gastric cancer.

  17. 悪性軟部肉腫に対するドキソルビシン治療後の心機能低下がパゾパニブ治療に及ぼす影響(後方視的解析)

    若山 祥之介, 大槻 泰史, 小峰 啓吾, 今井 源, 西條 憲, 高橋 昌宏, 高橋 信, 城田 英和, 高橋 雅信, 石岡 千加史

    日本内科学会雑誌　111　(Suppl.)　222-222　2022/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

    eISSN： 1883-2083

  18. Antibiotic Treatment Improves the Efficacy of Oxaliplatin-Based Therapy as First-Line Chemotherapy for Patients with Advanced Gastric Cancer: A Retrospective Study. International-journal

    Hiroo Imai, Ken Saijo, Keigo Komine, Reio Ueta, Ryunosuke Numakura, Shonosuke Wakayama, Sho Umegaki, Sakura Hiraide, Yoshufumi Kawamura, Yuki Kasahara, Kota Ohuchi, Masahiro Takahashi, Shin Takahashi, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Cancer management and research　14　1259-1266　2022

    DOI： 10.2147/CMAR.S353432 　

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    Purpose: One of the first-line treatment for gastric cancer patients is oxaliplatin, and the efficacy of this chemotherapeutic can be attenuated by the microbiome. In this study, we retrospectively evaluated whether treatment with antibiotics improved the efficacy of oxaliplatin-based chemotherapy in patients with advanced gastric cancer. Patients and Methods: Fifty-four patients were assigned to the antibiotic-treated group and 35 to the antibiotic-untreated group. Results: The response rate of oxaliplatin-based chemotherapy in the antibiotic-treated and antibiotic-untreated groups was 66.7% and 41.4%, respectively (p = 0.038). The median progression-free survival after oxaliplatin-based chemotherapy in the antibiotic-treated and antibiotic-untreated groups was 8.8 and 5.2 months, respectively (hazard ratio = 0.456, 95% confidence interval = 0.254-0.819; p = 0.007, Log rank test). Univariate and multivariate analyses revealed that antibiotic treatment was the only clinical parameter that correlated with the response to oxaliplatin. Conclusion: Antibiotic treatment could be used therapeutically to enhance the efficacy of oxaliplatin-based chemotherapy in patients with advanced gastric cancer.

  19. 進行大腸癌におけるregorafenibとtrifluridine/tipiracilの効果と安全性の検討

    笠原 佑記, 石岡 千加史, 高橋 雅信, 城田 英和, 高橋 信, 高橋 昌宏, 今井 源, 西條 憲, 小峰 啓吾, 大内 康太, 梅垣 翔, 平出 桜, 植田 怜男, 沼倉 龍之助, 若山 祥之介

    日本癌治療学会学術集会抄録集　59回　P3-2　2021/10

    Publisher: (一社)日本癌治療学会

  20. 地域におけるがんゲノム医療の啓蒙と今後の課題

    小峰 啓吾, 城田 英和, 石岡 千加史

    日本癌学会総会記事　80回　[SP1-1]　2021/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  21. クリニカルシーケンス向けITシステムの開発

    安田 知弘, 阿部 祥歩, 金森 英司, 横田 彩, 城田 英和, 小峰 啓吾, 石岡 千加史

    日本癌学会総会記事　80回　[P15-1]　2021/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  22. がん精密医療における効果的な薬剤推薦のための細胞組成分析

    阿部 祥歩, 安田 知弘, 金森 英司, 横田 彩, 城田 英和, 小峰 啓吾, 石岡 千加史

    日本癌学会総会記事　80回　[P15-2]　2021/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  23. Phase II study of trifluridine/tipiracil (TAS-102) therapy in elderly patients with colorectal cancer (T-CORE1401): geriatric assessment tools and plasma drug concentrations as possible predictive biomarkers. International-journal

    Masanobu Takahashi, Yasuhiro Sakamoto, Hisatsugu Ohori, Yasushi Tsuji, Michio Kuroki, Satoshi Kato, Kazunori Otsuka, Keigo Komine, Masahiro Takahashi, Shin Takahashi, Hidekazu Shirota, Kota Ouchi, Yoshikazu Takahashi, Hiroo Imai, Hiroyuki Shibata, Takashi Yoshioka, Masaki Tanaka, Hiroaki Yamaguchi, Takuhiro Yamaguchi, Hideki Shimodaira, Chikashi Ishioka

    Cancer chemotherapy and pharmacology　88　(3)　393-402　2021/09

    DOI： 10.1007/s00280-021-04277-3 　

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    PURPOSE: The current study aimed to determine the efficacy of trifluridine/tipiracil for elderly patients with advanced colorectal cancer. METHODS: This single-arm, open-label, multicenter, phase II study included elderly patients aged 65 years or more who had fluoropyrimidine-refractory advanced colorectal cancer and received trifluridine/tipiracil (70 mg/m2, days 1-5 and 8-12, every 4 weeks). The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), overall response rate (ORR), toxicities, association between efficacy and geriatric assessment scores, and association between toxicity and plasma drug concentrations. RESULTS: A total of 30 patients with a mean age of 73 years were enrolled. Median PFS was 2.3 months (95% confidence interval, 1.9-4.3 months), while median OS was 5.7 months (95% confidence interval, 3.7-8.9 months). Patients had an ORR of 0%, with 57% having stable disease. Grade 4 neutropenia was observed in 13% of the patients. Patients with a higher G8 score (15 or more) showed longer PFS than those with a lower G8 score (median 4.6 vs. 2.0 months; p = 0.047). Moreover, patients with grade 3 or 4 neutropenia showed higher maximum trifluridine concentrations than those with grade 1 or 2 neutropenia (mean 2945 vs. 2107 ng/mL; p = 0.036). DISCUSSION: The current phase II trial demonstrated that trifluridine/tipiracil was an effective and well-tolerated option for elderly patients with advanced colorectal cancer. Moreover, geriatric assessment tools and/or plasma drug concentration monitoring might be helpful in predicting the efficacy and toxicities in elderly patients receiving this drug. TRIAL REGISTRATION NUMBER: UMIN000017589, 15/May/2015 (The University Hospital Medical Information Network).

  24. Wide-Targeted Metabolome Analysis Identifies Potential Biomarkers for Prognosis Prediction of Epithelial Ovarian Cancer. International-journal

    Eiji Hishinuma, Muneaki Shimada, Naomi Matsukawa, Daisuke Saigusa, Bin Li, Kei Kudo, Keita Tsuji, Shogo Shigeta, Hideki Tokunaga, Kazuki Kumada, Keigo Komine, Hidekazu Shirota, Yuichi Aoki, Ikuko N Motoike, Jun Yasuda, Kengo Kinoshita, Masayuki Yamamoto, Seizo Koshiba, Nobuo Yaegashi

    Toxins　13　(7)　2021/06/30

    DOI： 10.3390/toxins13070461 　

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    Epithelial ovarian cancer (EOC) is a fatal gynecologic cancer, and its poor prognosis is mainly due to delayed diagnosis. Therefore, biomarker identification and prognosis prediction are crucial in EOC. Altered cell metabolism is a characteristic feature of cancers, and metabolomics reflects an individual's current phenotype. In particular, plasma metabolome analyses can be useful for biomarker identification. In this study, we analyzed 624 metabolites, including uremic toxins (UTx) in plasma derived from 80 patients with EOC using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Compared with the healthy control, we detected 77 significantly increased metabolites and 114 significantly decreased metabolites in EOC patients. Especially, decreased concentrations of lysophosphatidylcholines and phosphatidylcholines and increased concentrations of triglycerides were observed, indicating a metabolic profile characteristic of EOC patients. After calculating the parameters of each metabolic index, we found that higher ratios of kynurenine to tryptophan correlates with worse prognosis in EOC patients. Kynurenine, one of the UTx, can affect the prognosis of EOC. Our results demonstrated that plasma metabolome analysis is useful not only for the diagnosis of EOC, but also for predicting prognosis with the variation of UTx and evaluating response to chemotherapy.

  25. 当院のがんゲノム医療における認定遺伝カウンセラーの役割

    川村 真亜子, 津幡 真理, 杉山 育子, 小峰 啓吾, 新堀 哲也, 城田 英和, 青木 洋子, 石岡 千加史

    日本遺伝カウンセリング学会誌　42　(2)　71-71　2021/06

    Publisher: (一社)日本遺伝カウンセリング学会

    ISSN： 1347-9628

  26. 切除不能進行再発胃癌に対する化学療法の治療レジメンの選択とその効果に関する後ろ向き解析(A retrospective analysis of treatment sequence of chemotherapy for unresectable gastric cancer)

    高橋 信, 大内 康太, 笠原 佑記, 小峰 啓吾, 今井 源, 西條 憲, 高橋 昌宏, 城田 英和, 高橋 雅信, 石岡 千加史

    日本胃癌学会総会記事　93回　307-307　2021/03

    Publisher: (一社)日本胃癌学会

  27. Patients' understanding of communication about palliative care and health condition in Japanese patients with unresectable or recurrent cancer: a cross-sectional survey. International-journal

    Yusuke Hiratsuka, Takayuki Oishi, Mitsunori Miyashita, Tatsuya Morita, Jennifer W Mack, Masahiro Takahashi, Hidekazu Shirota, Kazunori Otsuka, Chikashi Ishioka, Akira Inoue

    Annals of palliative medicine　10　(3)　2650-2661　2021/03

    DOI： 10.21037/apm-20-2045 　

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    BACKGROUND: Understanding treatment goal is essential for decision-making among patients with unresectable/recurrent solid cancers. However, no previous studies in Japan have examined the association between patients' understanding and physicians' explanations. We aimed to examine agreement between patients' and physicians' reports of communication about palliative care and current health condition among patients with unresectable/recurrent cancer and explore factors associated with optimistic understanding in Japan. METHODS: In this cross-sectional, multicenter, observational survey in Japan, 178 patients with unresectable/ recurrent solid cancers and 16 physicians responded to questionnaires. The primary outcome was agreement between patients' and physicians' reports of communication about palliative care and current health condition. RESULTS: Of 56 patients who reported their communication about palliative care, 25/56 (44.6%) agreed with physician reports, and 31/56 (55.4%) were more optimistic than their physicians. Regarding current overall health condition, 45/122 (36.9%) patients gave reports that agreed with physicians' reports, and 77/122 (63.1%) were optimistic relative to physicians. Physicians' general approach about disclosure were not associated with patients' understanding. CONCLUSIONS: Fewer than 50% of Japanese patients with unresectable/recurrent cancer agreed with their physicians, whereas most others were more optimistic about palliative care communication and their health condition as compared to physicians. Effective communication is essential to ensure informed decisionmaking.

  28. HSVtk遺伝子導入腫瘍細胞を用いた生体内のアポトーシス細胞に対する免疫応答の解析

    梅垣 翔, 城田 英和, 石岡 千加史

    日本癌学会総会記事　79回　PJ12-7　2020/10

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  29. HSVtk遺伝子導入腫瘍細胞を用いた生体内のアポトーシス細胞に対する免疫応答の解析

    梅垣 翔, 城田 英和, 石岡 千加史

    日本癌学会総会記事　79回　PJ12-7　2020/10

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  30. A phase 2 basket trial of combination therapy with trastuzumab and pertuzumab in patients with solid cancers harboring human epidermal growth factor receptor 2 amplification (JUPITER trial). International-journal

    Kenta Takahashi, Eri Ishibashi, Toshio Kubo, Yohei Harada, Hideyuki Hayashi, Masayuki Kano, Yasushi Shimizu, Hidekazu Shirota, Yukiko Mori, Manabu Muto, Chikashi Ishioka, Hirotoshi Dosaka-Akita, Hisahiro Matsubara, Hiroshi Nishihara, Naoko Sueoka-Aragane, Shinichi Toyooka, Akihiro Hirakawa, Ukihide Tateishi, Satoshi Miyake, Sadakatsu Ikeda

    Medicine　99　(32)　e21457　2020/08/07

    DOI： 10.1097/MD.0000000000021457 　

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    INTRODUCTION: Human epidermal growth factor receptor 2 (HER2) gene amplification and mutations have emerged as oncogenic drivers and therapeutic targets not limited to breast and gastric cancers, but also in a variety of cancers. However, even if an actionable gene alteration is found, the incidence of HER2 amplification in these cancers is less than 5%. It is too difficult to conduct a conventional randomized, controlled trial in a rare fraction. Therefore, we have designed a organ-agnostic basket study, which covers a variety of solid cancers harboring HER2 amplification, in 1 study protocol. METHODS/DESIGN: This trial is a multicenter, single-arm, basket phase 2 study in Japan. Patients with solid cancers harboring HER2 amplification that have progressed with standard treatment, or rare cancers for which there is no standard treatment, will be eligible. Target cancers include bile duct, urothelial, uterine, ovarian, and other solid cancers where HER2 amplification is detected by comprehensive genomic profiling using next-generation sequencing technology. A total of 38 patients will be treated with combination therapy with trastuzumab and pertuzumab every 3 weeks until disease progression, unmanageable toxicity, death, or patient refusal. The primary endpoint is the objective response rate, and secondary endpoints are progression-free survival, overall survival, and duration of response. DISCUSSION: The aim of this trial is to evaluate the safety and efficacy of combination therapy with trastuzumab and pertuzumab in patients with locally advanced or metastatic, solid cancers harboring HER2 amplification. Instead of focusing on 1 organ type, our trial design uses a basket study focusing on HER2 amplification, regardless of the site or origin of the cancer. The results of our study will advance clinical and scientific knowledge concerning the treatment of locally advanced, rare solid cancers harboring HER2 amplification, using the combination of trastuzumab and pertuzumab. TRIAL REGISTRATION: This trial was registered in Japan Registry of Clinical Trials (jCRT) on February 25, 2019, as jRCT2031180150.

  31. [The Role of Core Hospital of Cancer Genomic Medicine and Regional Cooperation].

    Hidekazu Shirota, Keigo Komine

    Gan to kagaku ryoho. Cancer & chemotherapy　47　(8)　1149-1152　2020/08

    ISSN： 0385-0684

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    Two genomic profiling assays have been approved by Japanese national health insurance in December 2018. Japanese government assigned core hospitals, which can conduct molecular tumor board, called"expert panel"to make a therapeutic recommendation based on the genomic findings and concentrated the function of cancer genomic medicine. The genomic profiling tests under Japanese national health insurance system must be covered for the entire population. To eliminate regional disparities of such an advanced medicine, the infrastructure to spread cancer genomic medicine for collaborating among hospitals should be established. Here, we introduce our efforts to make regional collaboration in Tohoku University Hospital.

  32. Efficacy of modified FOLFOX6 chemotherapy for patients with unresectable pseudomyxoma peritonei.

    Sakura Hiraide, Keigo Komine, Yuko Sato, Kota Ouchi, Hiroo Imai, Ken Saijo, Masahiro Takahashi, Shin Takahashi, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    International journal of clinical oncology　25　(4)　774-781　2020/04

    DOI： 10.1007/s10147-019-01592-x 　

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    BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare malignancy, and there is insufficient evidence about systemic chemotherapy for this disease. METHODS: We retrospectively evaluated the efficacy and safety of a chemotherapeutic regimen with 5-fluorouracil and oxaliplatin (modified FOLFOX6, mFOLFOX6) for patients with unresectable pseudomyxoma peritonei. Patients who received the therapy between April 2000 and February 2019 at the Department of Medical Oncology, Tohoku University Hospital, were enrolled in this study. RESULTS: Eight patients were treated with mFOLFOX6. The sites of primary tumor were appendix in six patients, ovary in a patient, and urachus in a patient. Six patients received surgery. Seven patients had histologically high-grade PMP, and one patient had low-grade PMP. The median follow-up duration was 27.2 months. All the patients had non-measurable regions as the targets of tumor response. Non-complete response or non-progressive disease was observed in seven patients, with a disease control rate of 87.5%. The median progression-free survival and overall survival were 13.0 months and 27.9 months, respectively. An obvious reduction in the symptoms was observed in two patients. Five patients experienced decline in the serum tumor markers, CEA or CA19-9. The grade 3/4 toxicity that was observed was grade 4 neutropenia in one patient and grade 3 neutropenia in two patients. CONCLUSIONS: mFOLFOX6 might be an effective and tolerable treatment option for patients with unresectable PMP. To our knowledge, this is the first case series of mFOLFOX6 in patients with unresectable PMP and the first case series of systemic chemotherapy for Asian patients with unresectable PMP.

  33. Antibiotics Improve the Treatment Efficacy of Oxaliplatin-Based but Not Irinotecan-Based Therapy in Advanced Colorectal Cancer Patients. International-journal

    Hiroo Imai, Ken Saijo, Keigo Komine, Yuya Yoshida, Keiju Sasaki, Asako Suzuki, Kota Ouchi, Masahiro Takahashi, Shin Takahashi, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Journal of oncology　2020　1701326-1701326　2020

    DOI： 10.1155/2020/1701326 　

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    Background: Oxaliplatin and irinotecan are generally used to treat advanced colorectal cancer (CRC) patients. Antibiotics improve the cytotoxicity of oxaliplatin but not irinotecan in a colon cancer cell line in vitro. This study retrospectively assessed whether antibiotics improve the treatment efficacy of oxaliplatin- but not irinotecan-based therapy in advanced CRC patients. Patients and Methods. The medical records of 220 advanced CRC patients who underwent oxaliplatin- or irinotecan-based therapy were retrospectively reviewed. The oxaliplatin and irinotecan groups were further divided into antibiotic-treated (group 1) and antibiotic-untreated (group 2) subgroups. Results: In oxaliplatin groups 1 and 2, the response rate (RR) was 58.2% and 30.2%, while the disease control rate (DCR) was 92.5% and 64.2%, respectively; the median progression-free survival (PFS) was 10.5 months (95% confidence interval (CI) = 7.5-12.2) and 7.0 months (95% CI = 17.0-26.0), respectively, and the median overall survival (OS) was 23.8 months (95% CI = 5.1-9.1) and 17.4 months (95% CI = 13.1-24.9), respectively. In irinotecan groups 1 and 2, the RR was 17.8% and 20.0%, while the DCR was 75.6% and 69.1%, respectively; the median PFS was 8.2 months (95% CI = 6.2-12.7) and 7.9 months (95% CI = 12.0-23.0), respectively, and the median OS was 16.8 months (95% CI = 5.9-10.6) and 13.1 months (95% CI = 10.4-23.7), respectively. Conclusion: To improve the treatment efficacy of oxaliplatin-based therapy in advanced CRC patients, adding antibiotics is a potential therapeutic option.

  34. Contribution of Fcγ receptor IIB to creating a suppressive tumor microenvironment in a mouse model. International-journal

    Yuki Kasahara, Hidekazu Shirota, Sho Umegaki, Chikashi Ishioka

    Cancer immunology, immunotherapy : CII　68　(11)　1769-1778　2019/11

    DOI： 10.1007/s00262-019-02413-w 　

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    Various immune cells are recruited in the tumor microenvironment. It is well established that cellular immune responses, such as cytotoxic or suppressive activities, play an important role in regulating tumor growth and metastasis. However, the contribution of humoral immune responses against tumors is poorly understood. Fc receptors constitute critical elements for the up- or downregulation of immune responses through immune complexes. Here, we examined the potential role of the inhibitory Fc receptor, Fcγ receptor IIB (FcγRIIB), in tumor immunity using a mouse model. Our findings indicated that tumor-specific antibodies are induced in tumor-bearing mice and control tumor immunity. FcγRIIB deletion significantly improved both cellular and humoral immunity against tumors and delayed tumor growth. These findings indicated that spontaneous antibodies against tumors create a suppressive tumor microenvironment through FcγRIIB signaling, thus suggesting an attractive therapeutic target for cancer immunotherapy.

  35. Onco-Cardiologyとがん治療 がん薬物療法施行患者に発症した静脈血栓塞栓症に対するDOACの効果と安全性の検討

    小峰 啓吾, 高橋 雅信, 平出 桜, 山田 英晴, 吉田 裕也, 大槻 泰史, 佐藤 悠子, 大内 康太, 今井 源, 西條 憲, 高橋 昌宏, 高橋 信, 城田 英和, 千葉 奈津子, 石岡 千加史

    日本癌治療学会学術集会抄録集　57回　WS3-5　2019/10

    Publisher: (一社)日本癌治療学会

  36. 未治療切除不能・進行再発消化器癌におけるG8と生存期間に関する後方視的解析

    高橋 昌宏, 鈴木 朝子, 佐々木 啓寿, 吉田 裕也, 大内 康太, 佐藤 悠子, 小峰 啓吾, 今井 源, 西條 憲, 高橋 信, 城田 英和, 高橋 雅信, 石岡 千加史

    日本癌治療学会学術集会抄録集　57回　O17-6　2019/10

    Publisher: (一社)日本癌治療学会

  37. DICを合併した進行胃癌患者の予後関連因子

    佐藤 悠子, 高橋 信, 大内 康太, 鈴木 朝子, 佐々木 啓寿, 吉田 裕也, 小峰 啓吾, 今井 源, 西條 憲, 高橋 昌宏, 城田 英和, 高橋 雅信, 石岡 千加史

    日本癌治療学会学術集会抄録集　57回　P71-6　2019/10

    Publisher: (一社)日本癌治療学会

  38. 切除不能虫垂癌に対する化学療法の有効性の後方視的解析

    平出 桜, 小峰 啓吾, 佐藤 悠子, 大内 康太, 今井 源, 西條 憲, 高橋 昌宏, 高橋 信, 城田 英和, 高橋 雅信, 石岡 千加史

    日本癌治療学会学術集会抄録集　57回　P75-3　2019/10

    Publisher: (一社)日本癌治療学会

  39. CpG DNAとTGF-β中和抗体を併用する新規がん免疫療法の開発(TGF-beta blockade enhances the immunotherapeutic effect of CpG DNA in cancer)

    梅垣 翔, 城田 英和, 石岡 千加史

    日本癌学会総会記事　78回　P-1106　2019/09

    Publisher: 日本癌学会

    ISSN： 0546-0476

  40. Therapeutic Benefits of Ipilimumab among Japanese Patients with Nivolumab-Refractory Mucosal Melanoma: A Case Series Study.

    Ken Saijo, Hiroo Imai, Kota Ouchi, Yoshinari Okada, Yuko Sato, Keigo Komine, Masahiro Takahashi, Shin Takahashi, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    The Tohoku journal of experimental medicine　248　(1)　37-43　2019/05

    DOI： 10.1620/tjem.248.37 　

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    The antibodies targeting programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have provided survival benefits in patients with advanced malignant melanoma. The anti-PD-1 antibodies nivolumab and pembrolizumab are considered superior to the anti-CTLA-4 antibody ipilimumab as first-line therapy, suggesting that ipilimumab should be administered to patients with anti-PD-1 antibody-refractory melanoma in the second-line setting. However, there is limited evidence regarding the efficacy and safety of ipilimumab after disease progression on anti-PD-1 antibody therapy. Moreover, in patients with mucosal melanoma, a rare and aggressive subtype, evidence is extremely poor. This study aimed to clarify the efficacy and safety of ipilimumab among Japanese patients with nivolumab-refractory advanced mucosal melanoma. We retrospectively analyzed the seven patients with advanced mucosal melanoma who were treated with ipilimumab after disease progression on nivolumab at our hospital between September 2015 and December 2017. No patient achieved complete response or partial response to ipilimumab therapy. However, six patients achieved stable disease, and of these patients, three achieved a decline in the tumor size. All the three patients with a decline in tumor size developed grade 3 toxicity: two patients developed colitis and one patient experienced alanine aminotransferase elevation. The median progression-free survival (PFS) for prior nivolumab therapy was 148 days. The median PFS for ipilimumab therapy after disease progression with nivolumab was 193 days. The median overall survival was 661 days. In conclusion, although even partial response was undetectable with ipilimumab therapy, ipilimumab could produce additional PFS among nivolumab-refractory advanced mucosal melanoma patients.

  41. [Interinstitutional Collaboration for Molecular Tumor Boards].

    Keigo Komine, Hidekazu Shirota

    Gan to kagaku ryoho. Cancer & chemotherapy　46　(4)　626-629　2019/04

    ISSN： 0385-0684

    More details Close

    In Japan, "Designated Core Hospitals for Cancer Genomic Medicine" as leading hospitals on cancer genomic medicine and "Cooperative Hospitals for Cancer Genomic Medicine" which conduct cancer genomic medicine in each region are working together to promote cancer genomic medicine. Eleven institutions as the former and 135 institutions as the latter are currently designated. It is essential to hold a molecular tumor board, which is called "Expert Panel" in Japan, to provide cancer genomic medicine for patients. In the Expert Panel, the results of tumor sequencing are interpreted with clinical information, then recommended treatment and genetic information to be provided are determined. Holding Expert Panels is a duty of Designated Core Hospitals for Cancer Genomic Medicine and Cooperative Hospitals need to participate in it. In order to facilitate the Expert Panel, it is effective to share patient's information using well-managed Web system. Besides that, there are many tasks to be addressed by cooperation of Designated Core Hospitals and Cooperative Hospitals such as registration of patient's information in the Center for Cancer genomics and Advanced Therapeutics(C-CAT), correspondence to increasing genomic testing and nurturing specialized human resources involved in cancer genomic medicine. Interinstitutional collaboration should be more encouraged to propagate cancer genomic medicine.

  42. ドキソルビシンに関連した心筋障害に関する後方視的検討

    大槻 泰史, 高橋 信, 大内 康太, 小峰 啓吾, 今井 源, 西條 憲, 高橋 昌宏, 城田 英和, 高橋 雅信, 石岡 千加史

    日本内科学会雑誌　108　(Suppl.)　257-257　2019/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

    eISSN： 1883-2083

  43. Antibiotic therapy augments the efficacy of gemcitabine-containing regimens for advanced cancer: a retrospective study. International-journal

    Hiroo Imai, Ken Saijo, Keigo Komine, Yasufumi Otsuki, Kota Ohuchi, Yuko Sato, Akira Okita, Masahiro Takahashi, Shin Takahashi, Hidekazu Shirota, Masanobu Takahashi, Chikashi Ishioka

    Cancer management and research　11　7953-7965　2019

    DOI： 10.2147/CMAR.S215697 　

    More details Close

    Background: The addition of antibiotics reportedly augments the efficacy of gemcitabine (GEM) in tumor-bearing mice. However, whether this phenomenon is also observed in cancer patients remains unclear. In the present study, we aimed to assess whether antibiotics for treatment or prevention of infection augments treatment efficacies of GEM-containing regimens in patients with any type of cancer. Methods: Medical records of patients diagnosed with cancer histopathologically and treated with GEM-containing regimens (n=169) were retrospectively reviewed. Patients were assigned into two groups: antibiotics-untreated group (patients who were treated with GEM-containing regimens but without antibiotics) and antibiotics-treated group (patients who were treated with GEM-containing regimens plus antibiotics). Response rates, progression-free survival (PFS) time, and overall survival (OS) time were analyzed for each group. Results: The response rates of the antibiotics-untreated and antibiotics-treated groups with GEM-containing regimens were 15.1% and 27.6%, respectively. The median PFS times of the antibiotics-untreated and antibiotics-treated groups were 2.5 (95% CI: 1.86-3.73) and 4.9 (95% CI: 3.47-6.0) months, respectively. The median OS times of the antibiotics-untreated and antibiotics-treated groups were 7.53 (95% CI: 5.63-9.57) months and 13.83 (95% CI: 10.83-16.43) months, respectively. Conclusion: The addition of antibiotics augments the treatment efficacies of GEM-containing regimens, and it may be a potential therapeutic option to improve treatment efficacies of GEM-containing regimens in patients with advanced cancer.

  44. 頭頸部扁平上皮癌患者に対するnivolumabの有効性および安全性に関する後方視的検討

    西條 憲, 梅垣 翔, 高橋 昌宏, 今井 源, 岡田 佳也, 大内 康太, 小峰 啓吾, 佐藤 悠子, 高橋 信, 城田 英和, 高橋 雅信, 石岡 千加史

    日本癌治療学会学術集会抄録集　56回　O54-4　2018/10

    Publisher: (一社)日本癌治療学会

  45. FcγRIIBの抑制性腫瘍微小環境形成への役割(Contribution of FcγRIIB to creating suppressive tumor microenvironment)

    笠原 佑記, 城田 英和, 石岡 千加史

    日本癌学会総会記事　77回　295-295　2018/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  46. マウスメラノーマモデルにおけるHDAC/PI3K dual inhibitorによる抗PD-1抗体薬の抗腫瘍効果増強の検討(Enhancing efficacy of anti-PD-1 antibody by combination with an HDAC/PI3K dual inhibitor in a mouse model of melanoma)

    西條 憲, 今井 源, 近松 園子, 笠原 佑記, 城田 英和, 加藤 正, 石岡 千加史

    日本癌学会総会記事　77回　474-474　2018/09

    Publisher: (一社)日本癌学会

    ISSN： 0546-0476

  47. Retrospective analysis on the clinical outcomes of recombinant human soluble thrombomodulin for disseminated intravascular coagulation syndrome associated with solid tumors. Peer-reviewed

    Ouchi K, Takahashi S, Chikamatsu S, Ito S, Takahashi Y, Kawai S, Okita A, Kasahara Y, Okada Y, Imai H, Komine K, Saijo K, Takahashi M, Shirota H, Takahashi M, Gamoh M, Ishioka C

    Int J Clin Oncol.　23　(4)　790-798　2018/08

    DOI： 10.1007/s10147-018-1261-z 　

    ISSN： 1341-9625

    eISSN： 1437-7772

  48. Efficacy and Safety of Trastuzumab in Combination with S-1 and Cisplatin Therapy for Japanese Patients with HER2-Positive Advanced Gastric Cancer: Retrospective Analysis. Peer-reviewed

    Okita A, Imai H, Takahashi M, Takahashi H, Umegaki S, Kawamura Y, Hiraide S, Ouchi K, Sato Y, Okada Y, Komine K, Saijo K, Takahashi S, Takahashi M, Shirota H, Ohori H, Gamoh M, Ishioka C

    Tohoku J Exp Med.　245　(2)　123-129　2018/06

    DOI： 10.1620/tjem.245.123 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  49. Contribution of FcgRIIb to creating the suppressive tumor microenvironment Peer-reviewed

    Kasahara Yuki, Shirota Hidekazu, Ishioka Chikashi

    CANCER SCIENCE　109　281　2018/01

    ISSN： 1349-7006

  50. Predictive factors for the efficacy of the second taxane treatment in patients with advanced cancer. International-journal Peer-reviewed

    Imai H, Saijo K, Komine K, Kawamura Y, Hiraide S, Umegaki S, Okada Y, Ohuchi K, Sato Y, Takahashi M, Takahashi S, Shirota H, Takahashi M, Ishioka C

    Cancer management and research　10　3629-3636　2018

    DOI： 10.2147/CMAR.S170948 　

    ISSN： 1179-1322

  51. Blockade of TNFR2 signaling enhances the immunotherapeutic effect of CpG ODN in a mouse model of colon cancer. Peer-reviewed

    Nie Y, He J, Shirota H, Trivett AL, Yang, Klinman DM, Oppenheim JJ, Chen X

    Sci Signal.　11　511　2018/01

  52. IL-4 blockade alters the tumor microenvironment and augments the response to cancer immunotherapy in a mouse model Peer-reviewed

    Shuku-ei Ito, Hidekazu Shirota, Yuki Kasahara, Ken Saijo, Chikashi Ishioka

    CANCER IMMUNOLOGY IMMUNOTHERAPY　66　(11)　1485-1496　2017/11

    DOI： 10.1007/s00262-017-2043-6 　

    ISSN： 0340-7004

    eISSN： 1432-0851

  53. The G8 screening tool enhances prognostic value to ECOG performance status in elderly cancer patients: A retrospective, single institutional study Peer-reviewed

    Masahiro Takahashi, Masanobu Takahashi, Keigo Komine, Hideharu Yamada, Yuki Kasahara, Sonoko Chikamatsu, Akira Okita, Shukuei Ito, Kota Ouchi, Yoshinari Okada, Hiroo Imai, Ken Saijo, Hidekazu Shirota, Shin Takahashi, Takahiro Mori, Hideki Shimodaira, Chikashi Ishioka

    PLOS ONE　12　(6)　e0179694　2017/06

    DOI： 10.1371/journal.pone.0179694 　

    ISSN： 1932-6203

  54. Efficacy and safety of gemcitabine plus docetaxel in Japanese patients with unresectable or recurrent bone and soft tissue sarcoma: Results from a single-institutional analysis Peer-reviewed

    Masanobu Takahashi, Keigo Komine, Hiroo Imai, Yoshinari Okada, Ken Saijo, Masahiro Takahashi, Hidekazu Shirota, Hisatsugu Ohori, Shin Takahashi, Natsuko Chiba, Takahiro Mori, Hideki Shimodaira, Chikashi Ishioka

    PLOS ONE　12　(5)　e0176972　2017/05

    DOI： 10.1371/journal.pone.0176972 　

    ISSN： 1932-6203

  55. IL4 from T Follicular Helper Cells Downregulates Antitumor Immunity Peer-reviewed

    Hidekazu Shirota, Dennis M. Klinman, Shuku-ei Ito, Hiroyasu Ito, Masato Kubo, Chikashi Ishioka

    CANCER IMMUNOLOGY RESEARCH　5　(1)　61-71　2017/01

    DOI： 10.1158/2326-6066.CIR-16-0113 　

    ISSN： 2326-6066

    eISSN： 2326-6074

  56. Successful sequential treatment of a patient with advanced gastrointestinal stromal tumor using four different molecularly targeted drugs Peer-reviewed

    Sugiyama Shunsuke, Ishizuka Mariko, Takahashi Masanobu, Komine Keigo, Imai Hiroo, Saijo Ken, Takahashi Masahiro, Shirota Hidekazu, Takahashi Shin, Shimodaira Hideki, Ishioka Chikashi

    INTERNATIONAL CANCER CONFERENCE JOURNAL　5　(4)　163-167　2016/10

    DOI： 10.1007/s13691-016-0250-1 　

    ISSN： 2192-3183

  57. IL-4 modulate the tumor microenvironment and response to cancer therapies Peer-reviewed

    Ito Shuku-ei A, Shirota Hidekazu, Ishioka Chikashi

    CANCER RESEARCH　76　2016/07

    DOI： 10.1158/1538-7445.AM2016-1454 　

    ISSN： 0008-5472

  58. IL-4 derived from T follicular helper cells in tumor draining lymph nodes regulate myeloid cell properties and anti-tumor immunity Peer-reviewed

    Shirota Hidekazu, Klinman Dennis M, Ito Shuku-ei A, Ishioka Chikashi

    CANCER RESEARCH　76　2016/07

    DOI： 10.1158/1538-7445.AM2016-1455 　

    ISSN： 0008-5472

  59. Attainment of a Long-term Favorable Outcome by Sunitinib Treatment for Pancreatic Neuroendocrine Tumor and Renal Cell Carcinoma Associated with von Hippel-Lindau Disease Peer-reviewed

    Akihiro Kobayashi, Masanobu Takahashi, Hiroo Imai, Shoko Akiyama, Shunsuke Sugiyama, Keigo Komine, Ken Saijo, Masahiro Takahashi, Shin Takahashi, Hidekazu Shirota, Naomi Sato, Fumiyoshi Fujishima, Taro Shuin, Hideki Shimodaira, Chikashi Ishioka

    INTERNAL MEDICINE　55　(6)　629-634　2016

    DOI： 10.2169/internalmedicine.55.5796 　

    ISSN： 0918-2918

    eISSN： 1349-7235

  60. CpG oligonucleotides as cancer vaccine adjuvants Peer-reviewed

    Hidekazu Shirota, Debra Tross, Dennis M. Klinman

    Vaccines　3　(2)　390-407　2015/05/08

    Publisher: MDPI AG

    DOI： 10.3390/vaccines3020390 　

    ISSN： 2076-393X

  61. Effect of TLR Agonists on the Differentiation and Function of Human Monocytic Myeloid-Derived Suppressor Cells Peer-reviewed

    Jing Wang, Yuko Shirota, Defne Bayik, Hidekazu Shirota, Debra Tross, James L. Gulley, Lauren V. Wood, Jay A. Berzofsky, Dennis M. Klinman

    JOURNAL OF IMMUNOLOGY　194　(9)　4215-4221　2015/05

    DOI： 10.4049/jimmunol.1402004 　

    ISSN： 0022-1767

    eISSN： 1550-6606

  62. Efficacy and Safety of Carboplatin and Etoposide Combination Chemotherapy for Extrapulmonary Neuroendocrine Carcinoma: A Retrospective Case Series Peer-reviewed

    Hiroo Imai, Hidekazu Shirota, Akira Okita, Keigo Komine, Ken Saijo, Masahiro Takahashi, Shin Takahashi, Masanobu Takahashi, Hideki Shimodaira, Chikashi Ishioka

    CHEMOTHERAPY　61　(3)　111-116　2015

    DOI： 10.1159/000441551 　

    ISSN： 0009-3157

    eISSN： 1421-9794

  63. Efficacy and Safety Assessment of Paclitaxel in Patients with Docetaxel-Resistant Esophageal Squamous Cell Carcinoma Peer-reviewed

    Hiroo Imai, Keigo Komine, Shin Takahashi, Ken Saijo, Yoshinari Okada, Akihiro Kobayashi, Akira Okita, Sonoko Chikamatsu, Yuki Kasahara, Masahiro Takahashi, Takayuki Oishi, Hidekazu Shirota, Masanobu Takahashi, Hideki Shimodaira, Chikashi Ishioka

    CHEMOTHERAPY　61　(5)　262-268　2015

    DOI： 10.1159/000444122 　

    ISSN： 0009-3157

    eISSN： 1421-9794

  64. A RETROSPECTIVE ANALYSIS OF THE EFFICACY AND SAFETY OF REGORAFENIB IN PATIENTS WITH CHEMO-REFRACTORY COLORECTAL CANCER Peer-reviewed

    Oishi Takayuki, Takahashi Masanobu, Shiono Masatoshi, Takahashi Shin, Akiyama Shoko, Shirota Hidekazu, Shimodaira Hideki, Kato Shunsuke, Ishioka Chikashi

    ANNALS OF ONCOLOGY　25　2014/10

    DOI： 10.1093/annonc/mdu436.27 　

    ISSN： 0923-7534

  65. IFN-gamma AU-rich element removal promotes chronic IFN-gamma expression and autoimmunity in mice Peer-reviewed

    Deborah L. Hodge, Cyril Berthet, Vincenzo Coppola, Wolfgang Kastenmueller, Matthew D. Buschman, Paul M. Schaughency, Hidekazu Shirota, Anthony J. Scarzello, Jeff J. Subleski, Miriam R. Anver, John R. Ortaldo, Fanching Lin, Della A. Reynolds, Michael E. Sanford, Philipp Kaldis, Lino Tessarollo, Dennis M. Klinman, Howard A. Young

    JOURNAL OF AUTOIMMUNITY　53　33-45　2014/09

    DOI： 10.1016/j.jaut.2014.02.003 　

    ISSN： 0896-8411

    eISSN： 1095-9157

  66. Recent progress concerning CpG DNA and its use as a vaccine adjuvant Peer-reviewed

    Hidekazu Shirota, Dennis M. Klinman

    EXPERT REVIEW OF VACCINES　13　(2)　299-312　2014/02

    DOI： 10.1586/14760584.2014.863715 　

    ISSN： 1476-0584

    eISSN： 1744-8395

  67. TLR-9 agonist immunostimulatory sequence adjuvants linked to cancer antigens Peer-reviewed

    Hidekazu Shirota, Dennis M. Klinman

    Methods in Molecular Biology　1139　337-344　2014

    Publisher: Humana Press Inc.

    DOI： 10.1007/978-1-4939-0345-0_27 　

    ISSN： 1064-3745

  68. Use of CpG oligonucleotides for cancer immunotherapy and their effect on immunity in the tumor microenvironment Peer-reviewed

    Hidekazu Shirota, Dennis M. Klinman

    IMMUNOTHERAPY　5　(8)　787-789　2013/08

    DOI： 10.2217/IMT.13.70 　

    ISSN： 1750-743X

  69. beta-Defensin 2 and 3 Promote the Uptake of Self or CpG DNA, Enhance IFN-alpha Production by Human Plasmacytoid Dendritic Cells, and Promote Inflammation Peer-reviewed

    Poonam Tewary, Gonzalo de la Rosa, Neeraj Sharma, Luis G. Rodriguez, Sergey G. Tarasov, O. M. Zack Howard, Hidekazu Shirota, Folkert Steinhagen, Dennis M. Klinman, De Yang, Joost J. Oppenheim

    JOURNAL OF IMMUNOLOGY　191　(2)　865-874　2013/07

    DOI： 10.4049/jimmunol.1201648 　

    ISSN： 0022-1767

  70. Oligodeoxynucleotides Expressing Polyguanosine Motifs Promote Antitumor Activity through the Upregulation of IL-2 Peer-reviewed

    Nobuaki Kobayashi, Choongman Hong, Dennis M. Klinman, Hidekazu Shirota

    JOURNAL OF IMMUNOLOGY　190　(4)　1882-1889　2013/02

    DOI： 10.4049/jimmunol.1201063 　

    ISSN： 0022-1767

  71. Effect of CpG ODN on monocytic myeloid derived suppressor cells Peer-reviewed

    Hidekazu Shirota, Dennis M. Klinman

    ONCOIMMUNOLOGY　1　(5)　780-782　2012/08

    DOI： 10.4161/onci.19731 　

    ISSN： 2162-4011

  72. Intratumoral Injection of CpG Oligonucleotides Induces the Differentiation and Reduces the Immunosuppressive Activity of Myeloid-Derived Suppressor Cells Peer-reviewed

    Yuko Shirota, Hidekazu Shirota, Dennis M. Klinman

    JOURNAL OF IMMUNOLOGY　188　(4)　1592-1599　2012/02

    DOI： 10.4049/jimmunol.1101304 　

    ISSN： 0022-1767

  73. CpG-conjugated apoptotic tumor cells elicit potent tumor-specific immunity Peer-reviewed

    Hidekazu Shirota, Dennis M. Klinman

    CANCER IMMUNOLOGY IMMUNOTHERAPY　60　(5)　659-669　2011/05

    DOI： 10.1007/s00262-011-0973-y 　

    ISSN： 0340-7004

  74. A novel role for IL-22R1 as a driver of inflammation Peer-reviewed

    Ram Savan, Adelle P. McFarland, Della A. Reynolds, Lionel Feigenbaum, Karthika Ramakrishnan, Megan Karwan, Hidekazu Shirota, Dennis M. Klinman, Kieron Dunleavy, Stefania Pittaluga, Stephen K. Anderson, Raymond P. Donnelly, Wyndham H. Wilson, Howard A. Young

    BLOOD　117　(2)　575-584　2011/01

    DOI： 10.1182/blood-2010-05-285908 　

    ISSN： 0006-4971

  75. FDA guidance on prophylactic DNA vaccines: Analysis and recommendations Peer-reviewed

    Dennis M. Klinman, Sven Klaschik, Debra Tross, Hidekazu Shirota, Folkert Steinhagen

    VACCINE　28　(16)　2801-2805　2010/04

    DOI： 10.1016/j.vaccine.2009.11.025 　

    ISSN： 0264-410X

  76. Short- and long-term changes in gene expression mediated by the activation of TLR9 Peer-reviewed

    Sven Klaschik, Debra Tross, Hidekazu Shirota, Dennis M. Klinman

    MOLECULAR IMMUNOLOGY　47　(6)　1317-1324　2010/03

    DOI： 10.1016/j.molimm.2009.11.014 　

    ISSN： 0161-5890

  77. Immunostimulatory CpG oligonucleotides: Effect on gene expression and utility as vaccine adjuvants Peer-reviewed

    Dennis M. Klinman, Sven Klaschik, Koji Tomaru, Hidekazu Shirota, Debra Tross, Hidekazu Ikeuchi

    VACCINE　28　(8)　1919-1923　2010/02

    DOI： 10.1016/j.vaccine.2009.10.094 　

    ISSN： 0264-410X

  78. Contribution of IRF-3 mediated IFN beta production to DNA vaccine dependent cellular immune responses Peer-reviewed

    Hidekazu Shirota, Lev Petrenko, Toshio Hattori, Dennis M. Klinman

    VACCINE　27　(15)　2144-2149　2009/03

    DOI： 10.1016/j.vaccine.2009.01.134 　

    ISSN： 0264-410X

  79. Therapeutic Applications and Mechanisms Underlying the Activity of Immunosuppressive Oligonucleotides Peer-reviewed

    Dennis M. Klinman, Debbie Tross, Sven Klaschik, Hidekazu Shirota, Takeshi Sato

    OLIGONUCLEOTIDE THERAPEUTICS　1175　80-88　2009

    DOI： 10.1111/j.1749-6632.2009.04970.x 　

    ISSN： 0077-8923

  80. Synthetic oligonucleotides as modulators of inflammation Peer-reviewed

    Dennis Klinman, Hidekazu Shirota, Debra Tross, Takashi Sato, Sven Klaschik

    JOURNAL OF LEUKOCYTE BIOLOGY　84　(4)　958-964　2008/10

    DOI： 10.1189/jlb.1107775 　

    ISSN： 0741-5400

  81. Potential of Transfected Muscle Cells to Contribute to DNA Vaccine Immunogenicity. Peer-reviewed

    Shirota H, Petrenko L, Hong C, Klinman DM

    J Immunol.　179　(1)　329-336　2008/07

  82. Synergistic Up-regulation of Cytokine Genes by CpG Oligonucleotides Plus Poly (I:C) Peer-reviewed

    L. Petrenko, S. Klaschik, H. Shirota, D. M. Klinman

    PROCEEDINGS OF THE 7TH JOINT MEETING OF THE INTERNATIONAL MEETING OF THE INTERNATIONAL CYTOKINE SOCIETY AND THE INTERNATIONAL SOCIETY FOR INTERFERON AND CYTOKINE RESEARCH　65-71　2008

  83. Contribution of interferon-beta to the immune activation induced by double-stranded DNA Peer-reviewed

    H Shirota, KJ Ishii, H Takakuwa, DM Klinman

    IMMUNOLOGY　118　(3)　302-310　2006/07

    DOI： 10.1111/j.1365-2567.2006.02367.x 　

    ISSN： 0019-2805

    eISSN： 1365-2567

  84. Suppressive oligodeoxynucleotides protect mice from lethal endotoxic shock. Peer-reviewed

    Shirota H, Gursel I, Gursel M, Klinman DM

    J Immunol.　174　(8)　4579-4583　2005/11

    DOI： 10.4049/jimmunol.174.8.4579 　

  85. CpG oligodeoxynucleotides as a future vaccine for allergic diseases Peer-reviewed

    Kunio Sano, Hidekazu Shirota

    Allergology International　54　(1)　17-23　2005

    Publisher: Blackwell Publishing

    DOI： 10.2332/allergolint.54.17 　

    ISSN： 1323-8930

  86. Therapeutic potential of oligonucleotides expressing immunosuppressive TTAGGG motifs Peer-reviewed

    DM Klinman, Gursel, I, S Klaschik, L Dong, D Currie, H Shirota

    THERAPEUTIC OLIGONUCLEOTIDES: TRANSCRIPTIONAL AND TRANSLATIONAL STRATEGIES FOR SILENCING GENE EXPRESSION　1058　87-95　2005

    DOI： 10.1196/annals.1359.015 　

    ISSN： 0077-8923

  87. CpG oligodeoxynucleotides enhance neonatal resistance to Listeria infection Peer-reviewed

    S Ito, KI Ishii, M Gursel, H Shirotra, A Ihata, DM Klinman

    JOURNAL OF IMMUNOLOGY　174　(2)　777-782　2005/01

    ISSN： 0022-1767

  88. Suppressive oligodeoxynucleotides inhibit Th1 differentiation by blocking IFN-gamma- and IL-12-mediated signaling Peer-reviewed

    H Shirota, M Gursel, DM Klinman

    JOURNAL OF IMMUNOLOGY　173　(8)　5002-5007　2004/10

    ISSN： 0022-1767

  89. CpG oligodeoxynucleotides improve the survival of pregnant and fetal mice following Listeria monocytogenes infection Peer-reviewed

    S Ito, KJ Ishii, H Shirota, DM Klinman

    INFECTION AND IMMUNITY　72　(6)　3543-3548　2004/06

    DOI： 10.1128/IAI.72.6.3543-3548.2004 　

    ISSN： 0019-9567

  90. Oligodeoxynucleotides without CpG motifs work as adjuvant for the induction of Th2 differentiation in a sequence-independent manner Peer-reviewed

    K Sano, H Shirota, T Terui, T Hattori, G Tamura

    JOURNAL OF IMMUNOLOGY　170　(5)　2367-2373　2003/03

    ISSN： 0022-1767

  91. B cells capturing antigen conjugated with CpG oligodeoxynucleotides induce Th1 cells by elaborating IL-12 Peer-reviewed

    H Shirota, K Sano, N Hirasawa, T Terui, K Ohuchi, T Hattori, G Tamura

    JOURNAL OF IMMUNOLOGY　169　(2)　787-794　2002/07

    ISSN： 0022-1767

  92. TGF-beta-producing CD4(+) mediastinal lymph node cells obtained from mice tracheally tolerized to ovalbumin (OVA) suppress both Th1-and Th2-induced cutaneous inflammatory responses to OVA by different mechanisms Peer-reviewed

    T Terui, K Sano, H Shirota, N Kunikata, M Ozawa, M Okada, M Honda, G Tamura, H Tagami

    JOURNAL OF IMMUNOLOGY　167　(7)　3661-3667　2001/10

    ISSN： 0022-1767

  93. Production and pharmacologic modulation of the granulocyte-associated allergic responses to ovalbumin in murine skin models induced by injecting ovalbumin-specific Th1 or Th2 cells Peer-reviewed

    T Terui, K Sano, M Okada, H Shirota, M Honda, M Ozawa, N Hirasawa, G Tamura, H Tagami

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　117　(2)　236-243　2001/08

    DOI： 10.1046/j.0022-202X.2001.01375.x 　

    ISSN： 0022-202X

  94. Novel roles of CpG oligodeoxynucleotides as a leader for the sampling and presentation of CpG-tagged antigen by dendritic cells Peer-reviewed

    H Shirota, K Sano, N Hirasawa, T Terui, K Ohuchi, T Hattori, K Shirato, G Tamura

    JOURNAL OF IMMUNOLOGY　167　(1)　66-74　2001/07

    ISSN： 0022-1767

  95. Regulation of murine airway eosinophilia and Th2 cells by antigen-conjugated CpG oligodeoxynucleotides as a novel antigen-specific immunomodulator Peer-reviewed

    H Shirota, K Sano, T Kikuchi, G Tamura, K Shirato

    JOURNAL OF IMMUNOLOGY　164　(11)　5575-5582　2000/06

    ISSN： 0022-1767

  96. Regulation of T-helper type 2 cell and airway eosinophilia by transmucosal coadministration of antigen and oligodeoxynucleotides containing CpG motifs Peer-reviewed

    H Shirota, K Sano, T Kikuchi, G Tamura, K Shirato

    AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY　22　(2)　176-182　2000/02

    ISSN： 1044-1549

  97. Transforming growth factor-beta secreted from CD4(+) T cells ameliorates antigen-induced eosinophilic inflammation - A novel high-dose tolerance in the trachea Peer-reviewed

    K Haneda, K Sano, G Tamura, H Shirota, Y Ohkawara, T Sato, S Habu, K Shirato

    AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY　21　(2)　268-274　1999/08

    ISSN： 1044-1549

Show all ︎Show first 5

Misc. 56

  1. Characterization of plasma metabolomics and proteomics profiling in patients with CRP-positive squamous cell carcinoma

    岩崎智行, 菱沼英史, 菱沼英史, 城田英和, 城田英和, 笠原佑記, 笠原佑記, 梅垣翔, 佐々木啓寿, 佐々木啓寿, 石岡千加史, 石岡千加史, 石岡千加史

    日本臨床腫瘍学会学術集会(CD-ROM)　21st　2024

  2. Efficacy and safety of DOAC for treatments of VTE in patients undergoing cancer drug treatment

    小峰啓吾, 高橋雅信, 高橋雅信, 岩崎智行, 岩崎智行, 大内康太, 吉田裕也, 吉田裕也, 沼倉龍之助, 沼倉龍之助, 小寺修仁, 小寺修仁, 若山祥之介, 若山祥之介, 植田怜男, 植田怜男, 佐々木啓寿, 佐々木啓寿, 斎藤里佳, 川村佳史, 梅垣翔, 笠原佑記, 笠原佑記, 今井源, 西條憲, 城田英和, 城田英和, 千葉奈津子, 石岡千加史, 石岡千加史, 石岡千加史

    日本臨床腫瘍学会学術集会(CD-ROM)　20th　2023

  3. Characterization of plasma metabolomics and proteomics profiling in patients with CRP-positive squamous cell carcinoma

    岩崎智行, 菱沼英史, 菱沼英史, 城田英和, 城田英和, 笠原佑記, 笠原佑記, 梅垣翔, 梅垣翔, 佐々木啓寿, 佐々木啓寿, 石岡千加史, 石岡千加史, 石岡千加史

    日本癌学会学術総会抄録集(Web)　82nd　2023

  4. Chemoradiotherapy for metastatic primary cardiac angiosarcoma

    山本貴也, 城田英和, 井上千裕, 松下晴雄, 梅澤玲, 石川陽二郎, 石岡千加史, 神宮啓一

    臨床放射線　64　(11)　1369‐1374　2019/10/10

    DOI： 10.18888/rp.0000001033 　

    ISSN： 0009-9252

  5. Adoption of multigene panel testing for hereditary cancer "CancerNext" in Tohoku University Hospital

    Keigo Komine, Masanobu Takahashi, Sakura Hiraide, Hideharu Yamada, Mari Tsubata, Masahiro Takahashi, Shin Takahashi, Hidekazu Shirota, Tetsuya Niihori, Yoko Aoki, Chikashi Ishioka

    ANNALS OF ONCOLOGY　30　2019/10

    DOI： 10.1093/annonc/mdz338.040 　

    ISSN： 0923-7534

    eISSN： 1569-8041

  6. System maintenance of the core hospital for cancer genome medical care: action in the Tohoku University Hospital

    Chikashi Ishioka, Muneaki Shimada, Hidekazu Shirota, Hideki Tokunaga, Keigo Komine, Toru Furukawa, Nobuo Yaegashi

    CANCER SCIENCE　109　612-612　2018/12

    ISSN： 1349-7006

  7. Three cases of venous thromboembolism in advanced cancer patients

    Keigo Komine, Masanobu Takahashi, Sakura Hiraide, Sho Umegaki, Yoshifumi Kawamura, Hideharu Yamada, Akira Okita, Sonoko Chikamatsu, Yuki Kasahara, Yoshinari Okada, Hiroo Imai, Ken Saijo, Masahiro Takahashi, Hidekazu Shirota, Chikashi Ishioka

    ANNALS OF ONCOLOGY　29　8-8　2018/10

    ISSN： 0923-7534

    eISSN： 1569-8041

  8. 日本におけるがんゲノム医療体制の構築 がんゲノム医療中核拠点病院の体制整備 東北大学病院の取り組み(Development of Cancer Genomic Medicine Platform in Japan System maintenance of the core hospital for cancer genome medical care: action in the Tohoku University Hospital)

    石岡 千加史, 島田 宗昭, 城田 英和, 徳永 英樹, 小峰 啓吾, 古川 徹, 八重樫 伸生

    日本癌学会総会記事　77回　1045-1045　2018/09

    Publisher: 日本癌学会

    ISSN： 0546-0476

  9. 切除不能進行・再発副腎皮質癌に対するM‐EDP療法の効果と安全に関する後方視的検討

    川村佳史, 西條憲, 今井源, 城田英和, 近松園子, 岡田佳也, 笠原佑記, 梅垣翔, 高橋雅信, 石岡千加史

    日本内科学会雑誌　107　(Suppl.)　270-270　2018/02/20

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

    eISSN： 1883-2083

  10. 固形がんに合併した播種性血管内凝固症候群(DIC)に対する組換え型トロンボモデュリンアルファ(rTM)の治療成績に関する後ろ向き解析

    大内康太, 高橋信, 近松園子, 伊藤祝栄, 高橋義和, 高橋昌宏, 城田英和, 高橋雅信, 蒲生真紀夫, 石岡千加史

    日本内科学会雑誌　107　(Suppl.)　230-230　2018/02/20

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  11. 骨転移を伴う消化器癌及び希少がん患者における、デノスマブとゾレドロン酸の効果比較

    川村 佳史, 今井 源, 西條 憲, 小峰 啓吾, 岡田 佳也, 大内 康太, 山田 英晴, 高橋 昌宏, 高橋 信, 高橋 雅信, 城田 英和, 石岡 千加史

    日本癌治療学会学術集会抄録集　55回　P40-6　2017/10

    Publisher: (一社)日本癌治療学会

  12. 進行・再発尿膜管癌に対しFOLFIRIおよびmFOLFOX6療法を施行した5症例の検討

    平出 桜, 小峰 啓吾, 佐藤 悠子, 大内 康太, 岡田 佳也, 今井 源, 西條 憲, 高橋 昌宏, 高橋 信, 城田 英和, 高橋 雅信, 石岡 千加史

    日本癌治療学会学術集会抄録集　55回　P50-1　2017/10

    Publisher: (一社)日本癌治療学会

  13. FcγIIBの腫瘍微小環境形成への役割

    笠原 佑記, 城田 英和, 石岡 千加史

    日本癌学会総会記事　76回　P-1221　2017/09

    Publisher: 日本癌学会

    ISSN： 0546-0476

  14. 網羅的遺伝子発現解析による進行・再発大腸癌の免疫学的特徴の検討

    笠原 佑記, 城田 英和, 井上 正広, 高橋 信, 石岡 千加史

    日本内科学会雑誌　106　(Suppl.)　236-236　2017/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  15. 網羅的遺伝子発現解析による進行・再発大腸癌の免疫学的特徴の検討

    笠原 佑記, 城田 英和, 井上 正広, 高橋 信, 石岡 千加史

    日本内科学会雑誌　106　(Suppl.)　236-236　2017/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  16. ニボルマブ不応進行悪性黒色腫患者に対するイピリムマブ療法の効果と安全性についての後方視的検討

    西條憲, 近松園子, 大内康太, 岡田佳也, 今井源, 高橋雅信, 城田英和, 下平秀樹, 森隆弘, 石岡千加史

    日本臨床腫瘍学会学術集会(CD-ROM)　15th　ROMBUNNO.P1‐291　2017

  17. 大腸 免疫療法の進化 大腸癌網羅的遺伝子発現解析による免疫学的な検討

    笠原 佑記, 城田 英和, 井上 正広, 高橋 信, 石岡 千加史

    日本癌治療学会学術集会抄録集　54回　MS62-2　2016/10

    Publisher: (一社)日本癌治療学会

  18. 大腸 免疫療法の進化 大腸癌網羅的遺伝子発現解析による免疫学的な検討

    笠原 佑記, 城田 英和, 井上 正広, 高橋 信, 石岡 千加史

    日本癌治療学会学術集会抄録集　54回　MS62-2　2016/10

    Publisher: (一社)日本癌治療学会

  19. 高齢進行再発消化器癌患者におけるG8スクリーニングツール

    高橋 昌宏, 小林 輝大, 沖田 啓, 佐藤 悠子, 高橋 信, 高橋 雅信, 城田 英和, 下平 秀樹, 石岡 千加史

    日本内科学会雑誌　105　(Suppl.)　232-232　2016/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  20. 切除不能膵癌におけるGemcitabine、nab-Paclitaxel併用療法の有効性および安全性に関する後方視的検討

    岡田 佳也, 小峰 啓吾, 今井 源, 西條 憲, 高橋 昌宏, 高橋 信, 高橋 雅信, 城田 英和, 下平 秀樹, 石岡 千加史

    日本内科学会雑誌　105　(Suppl.)　233-233　2016/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  21. 切除不能進行再発大腸癌におけるTAS-102とregorafenib投与例の効果と安全性に関する後方視的検討

    笠原 佑記, 小峰 啓吾, 下平 秀樹, 城田 英和, 高橋 雅信, 高橋 信, 高橋 昌宏, 石岡 千加史

    日本内科学会雑誌　105　(Suppl.)　240-240　2016/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  22. 濾胞性ヘルパーT細胞から産生されるIL-4は抗腫瘍免疫を抑制する

    城田 英和, Klinman Dennis, 伊藤 祝栄, 石岡 千加史

    日本癌学会総会記事　74回　P-1071　2015/10

    Publisher: 日本癌学会

    ISSN： 0546-0476

  23. 腫瘍微小環境におけるIL-4の役割と抗腫瘍治療効果

    伊藤 祝栄, 城田 英和, 石岡 千加史

    日本癌学会総会記事　74回　P-1072　2015/10

    Publisher: 日本癌学会

    ISSN： 0546-0476

  24. 切除不能進行再発大腸癌に対するregorafenibとTAS102の治療効果に関する後方視的検討

    小峰 啓吾, 小林 輝大, 伊藤 祝栄, 大石 隆之, 岡田 佳也, 今井 源, 西條 憲, 高橋 昌宏, 高橋 雅信, 高橋 信, 城田 英和, 千葉 奈津子, 下平 秀樹, 森 隆弘, 石岡 千加史

    日本癌治療学会誌　50　(3)　2417-2417　2015/09

    Publisher: (一社)日本癌治療学会

    ISSN： 0021-4671

  25. 東北大学病院腫瘍内科における神経内分泌癌への白金製剤+エトポシド併用療法の検討

    沖田 啓, 今井 源, 笠原 佑記, 近松 園子, 大石 隆之, 岡田 佳也, 小峰 啓吾, 西條 憲, 高橋 昌宏, 高橋 信, 高橋 雅信, 城田 英和, 下平 秀樹, 石岡 千加史

    日本癌治療学会誌　50　(3)　2559-2559　2015/09

    Publisher: (一社)日本癌治療学会

    ISSN： 0021-4671

  26. 東北大学腫瘍内科における消化管間質腫瘍(GIST)に対する分子標的治療後の効果と安全性に関する後方視的解析

    杉山 俊輔, 小峰 啓吾, 今井 源, 西條 憲, 高橋 昌宏, 城田 英和, 高橋 信, 高橋 雅信, 下平 秀樹, 石岡 千加史

    日本内科学会雑誌　104　(Suppl.)　142-142　2015/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  27. 進行再発胆道癌におけるゲムシタビン+シスプラチン(GEM+CDDP)併用療法の治療効果と安全性

    下平 秀樹, 杉山 俊輔, 高橋 雅信, 小峰 啓吾, 西條 憲, 今井 源, 城田 英和, 高橋 昌宏, 高橋 信, 石岡 千加史

    日本内科学会雑誌　104　(Suppl.)　142-142　2015/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  28. 東北大学病院腫瘍内科における肺外神経内分泌癌(NEC)に対する化学療法の後方視的解析

    今井 源, 小林 輝大, 城田 英和, 杉山 俊輔, 小峰 啓吾, 高橋 昌宏, 西條 憲, 高橋 信, 高橋 雅信, 石岡 千加史

    日本内科学会雑誌　104　(Suppl.)　238-238　2015/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  29. 治癒切除不能進行膵癌11症例に対するFOLFIRINOX療法の有効性と安全性に関する後方視的検討

    小林 輝大, 高橋 雅信, 杉山 俊輔, 小峰 啓吾, 西條 憲, 今井 源, 高橋 信, 城田 英和, 下平 秀樹, 石岡 千加史

    日本内科学会雑誌　104　(Suppl.)　283-283　2015/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  30. 小腸癌に対する5FU系薬剤による治療成績の後方視的解析

    今井源, 西條憲, 小峰啓吾, 小林輝大, 高橋信, 高橋雅信, 城田英和, 高橋昌宏, 石岡千加史

    日本臨床腫瘍学会学術集会(CD-ROM)　13th　ROMBUNNO.P2-8-6　2015

  31. 軟部肉腫に対するドキソルビシン+イホスファマイド併用療法の治療成績についての後方視的検討

    西條憲, 西條憲, 伊藤祝栄, 伊藤祝栄, 小峰啓吾, 小峰啓吾, 今井源, 今井源, 城田英和, 城田英和, 高橋昌宏, 高橋昌宏, 高橋信, 高橋信, 高橋雅信, 高橋雅信, 下平秀樹, 下平秀樹, 石岡千加史, 石岡千加史

    日本臨床腫瘍学会学術集会(CD-ROM)　13th　ROMBUNNO.P3-9-58　2015

  32. 治癒切除不能進行膵癌におけるFOLFIRINOX療法の有効性および安全性に関する後方視的検討

    小林輝大, 小林輝大, 高橋雅信, 杉山俊輔, 西條憲, 今井源, 高橋昌宏, 高橋信, 城田英和, 下平秀樹, 下平秀樹, 石岡千加史, 石岡千加史

    日本臨床腫瘍学会学術集会(CD-ROM)　13th　ROMBUNNO.P1-8-10　2015

  33. Polythymine oligonucleotides inhibit tumor growth through the induction of IFN alpha

    Nobuaki Kobayashi, Hidekazu Shirota, Yoko Ichiki, Kiyoshi Sakasai, Yasushi Ichikawa, Takeshi Kaneko, Yoshiaki Ishigatsubo

    CANCER RESEARCH　74　(19)　2014/10

    DOI： 10.1158/1538-7445.AM2014-2576 　

    ISSN： 0008-5472

    eISSN： 1538-7445

  34. トール様レセプターによるヒトMDSCの分化誘導(Effect of TLR Ligation on the Differentiation and Function of Human mMDSC)

    城田 英和, 石岡 千加史, クラインマン・デニス

    日本癌学会総会記事　73回　P-1241　2014/09

    Publisher: 日本癌学会

    ISSN： 0546-0476

  35. 進行再発胆道癌におけるゲムシタビン+シスプラチン併用療法の治療効果と安全性

    下平 秀樹, 高橋 信, 高橋 雅信, 高橋 昌宏, 西條 憲, 城田 英和, 小峰 啓吾, 今井 源, 森 隆弘, 石岡 千加史

    日本癌治療学会誌　49　(3)　1348-1348　2014/06

    Publisher: (一社)日本癌治療学会

    ISSN： 0021-4671

  36. 骨転移を有する進行癌35例に対するデノスマブの有効性と安全性に関する後ろ向き解析

    佐藤 悠子, 西條 憲, 井上 正広, 添田 大司, 坂本 康寛, 塩野 雅俊, 高橋 雅信, 高橋 信, 角道 祐一, 城田 英和, 秋山 聖子, 下平 秀樹, 森 隆弘, 加藤 俊介, 石岡 千加史

    日本癌治療学会誌　49　(3)　2124-2124　2014/06

    Publisher: (一社)日本癌治療学会

    ISSN： 0021-4671

  37. 進行再発大腸癌14例に対するレゴラフェニブの有効性と安全性に関する後方視的検討

    大石 隆之, 高橋 雅信, 吉野 優樹, 李 仁, 塩野 雅俊, 高橋 昌宏, 城田 英和, 下平 秀樹, 加藤 俊介, 石岡 千加史

    日本癌治療学会誌　49　(3)　2417-2417　2014/06

    Publisher: (一社)日本癌治療学会

    ISSN： 0021-4671

  38. Autoimmunity in interferon-gamma AU-rich element deleted-mice is associated with loss of marginal zone B cells and macrophages.

    Deborah Hodge, Cyril Berthet, Vincenzo Coppola, Wolfgang Kastenmueller, Matthew Buschman, Hidekazu Shirota, Paul Schaughency, Miriam Anver, Della Reynolds, Michael Sanford, Philipp Kaldis, Howard Young

    JOURNAL OF IMMUNOLOGY　192　2014/05

    ISSN： 0022-1767

    eISSN： 1550-6606

  39. 家族性大腸腫瘍 進行大腸癌に対する化学療法を行ったLynch症候群疑いの4例

    下平 秀樹, 高橋 雅信, 西條 憲, 小峰 啓吾, 今井 源, 杉山 俊輔, 高橋 昌宏, 城田 英和, 高橋 信, 森 隆弘, 石岡 千加史

    家族性腫瘍　14　(2)　A25-A25　2014/05

    Publisher: 日本家族性腫瘍学会

    ISSN： 1346-1052

  40. 標準治療抵抗性となった進行再発大腸癌へのレゴラフェニブ投与例の検討

    大石 隆之, 高橋 雅信, 塩野 雅俊, 高橋 信, 秋山 聖子, 城田 英和, 下平 秀樹, 加藤 俊介, 石岡 千加史

    日本内科学会雑誌　103　(Suppl.)　249-249　2014/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  41. 標準治療抵抗性の進行再発大腸癌14例に対するレゴラフェニブの効果と安全性に関する後ろ向き検討

    大石隆之, 高橋雅信, 吉野優樹, LEE Jin, 塩野雅俊, 高橋昌宏, 城田英和, 下平秀樹, 加藤俊介, 石岡千加史

    日本臨床腫瘍学会学術集会(CD-ROM)　12th　ROMBUNNO.P1-12-2　2014

  42. CpG ODNの投与は腫瘍内のMDSCの分化を誘導しT細胞抑制能力を消失させる(Intra-tumoral injection of CpG ODN induces the differentiation and reduces the immunosuppressive activity of MDSC)

    城田 英和, 石岡 千加史, クラインマン・デニス

    日本癌学会総会記事　72回　146-146　2013/10

    Publisher: 日本癌学会

    ISSN： 0546-0476

  43. Loss of IFN-gamma 3 ' untranslated region AU-rich element affects B220+cell populations in novel murine lupus model

    Deborah L. Hodge, Cyril Berthet, Vincenzo Coppola, Hidekazu Shirota, Della Reynolds, Michael Sanford, Fanching Lin, Dennis M. Klinman, Howard A. Young

    CYTOKINE　63　(3)　271-271　2013/09

    DOI： 10.1016/j.cyto.2013.06.123 　

    ISSN： 1043-4666

  44. 包巣状軟部肉腫に対してPazopanibが奏効した二例

    伊藤 祝栄, 加藤 俊介, 保坂 正美, 綿貫 宗則, 鈴木 堅太郎, 林 耕宇, 秋山 聖子, 高橋 信, 高橋 雅信, 添田 大司, 井上 正広, 城田 英和, 森 隆弘, 下平 秀樹, 石岡 千加史

    日本癌治療学会誌　48　(3)　2078-2078　2013/09

    Publisher: (一社)日本癌治療学会

    ISSN： 0021-4671

  45. 神経線維腫症1型に併発した悪性腫瘍に対し化学療法を行った5例

    下平 秀樹, 西條 憲, 添田 大司, 井上 正広, 塩野 雅俊, 城田 英和, 高橋 信, 高橋 雅信, 加藤 俊介, 石岡 千加史

    家族性腫瘍　13　(2)　A75-A75　2013/05

    Publisher: 日本家族性腫瘍学会

    ISSN： 1346-1052

  46. 肺外神経内分泌癌に対する化学療法の後方視的検討

    坂本 康寛, 秋山 聖子, 城田 英和, 井上 正広, 岡田 佳也, 杉山 俊輔, 齋藤 菜穂子, 大石 隆之, 加藤 俊介, 石岡 千加史

    日本内科学会雑誌　102　(Suppl.)　184-184　2013/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  47. 当科にてデノスマブを投与した転移性骨腫瘍の検討

    佐藤 悠子, 加藤 俊介, 秋山 聖子, 城田 英和, 井上 正広, 岡田 佳也, 杉山 俊輔, 齋藤 菜穂子, 大石 隆之, 石岡 千加史

    日本内科学会雑誌　102　(Suppl.)　196-196　2013/02

    Publisher: (一社)日本内科学会

    ISSN： 0021-5384

  48. Loss of IFN-gamma 3 ' untranslated region AU-rich element affects B220+B cell and plasmacytoid dendritic cell populations in novel murine lupus model

    Deborah Hodge, Cyril Berthet, Vincenzo Coppola, Hidekazu Shirota, Della Reynolds, Dennis Klinman, Howard Young

    JOURNAL OF IMMUNOLOGY　188　2012/05

    ISSN： 0022-1767

  49. Loss of Ifn-g 3 &apos; Untranslated Region Au-rich Element Affects b220+b Cell and Plasmacytoid Dendritic cell Populations in a Novel Murine Lupus Model

    Deborah L. Hodge, Cyril Berthet, Vincenzo Coppola, Hidekazu Shirota, Della Reynolds, Dennis M. Klinman, Howard A. Young

    CYTOKINE　56　(1)　100-100　2011/10

    DOI： 10.1016/j.cyto.2011.07.389 　

    ISSN： 1043-4666

  50. Lactoferrin inhibits DNA-induced IFN-alpha production by human plasmacytoid dendritic cells

    Poonam Tewary, Gonzalo dela Rosa, Luis Rodriguez, Elena Riboldi, Hidekazu Shirota, Karel Patrek, Dennis Klinman, De Yang, Joost Oppenheim

    JOURNAL OF IMMUNOLOGY　186　2011/04

    ISSN： 0022-1767

    eISSN： 1550-6606

  51. Role of Interferon Regulatory Factor (IRF)-3 in lung tumor microenvironment

    Hidekazu Shirota, Dennis M. Klinman

    CANCER RESEARCH　71　2011/04

    DOI： 10.1158/1538-7445.AM2011-412 　

    ISSN： 0008-5472

    eISSN： 1538-7445

  52. A novel role of IL-22R1 as a possible driver of inflammation in ALK(+) anaplastic large cell lymphoma

    Ram Savan, Della A. Reynolds, Adelle P. McFarland, Lionel Feigenbaum, Karthika Ramakrishnan, Hidekazu Shirota, Dennis M. Klinman, Kieron Dunleavy, Stefania Pittaluga, Stephen K. Anderson, Raymond P. Donnelly, Wyndham H. Wilson, Howard Young

    CYTOKINE　52　(1-2)　69-69　2010/10

    DOI： 10.1016/j.cyto.2010.07.291 　

    ISSN： 1043-4666

  53. Targeted removal of IFN-gamma 3 &apos; untranslated region AU-rich element alters B cell function resulting in lupus-like disease in C57BL6 mice

    Deborah L. Hodge, Cyril Berthet, Jeff Subleski, Vincenzo Coppola, Hidekazu Shirota, Matthew Buschman, Catherine Razzook, Howard A. Young

    CYTOKINE　52　(1-2)　5-5　2010/10

    DOI： 10.1016/j.cyto.2010.07.025 　

    ISSN： 1043-4666

  54. Ectopic expression of Interleukin-22 receptors (IL-22R1) on lymphocytes induces multi-organ inflammation and premature death

    Ram Savan, Della Reynolds, AdeIle McFarland, Lionel Feigenbaum, Karthika Ramakrishnan, Hidekazu Shirota, Dennis Klinman, Raymond Donnelly, Howard Young

    JOURNAL OF IMMUNOLOGY　184　2010/04

    ISSN： 0022-1767

    eISSN： 1550-6606

  55. CpG-conjugated apoptotic tumor cells elicit potent tumor immunity

    Hidekazu Shirota, Dennis Klinman

    JOURNAL OF IMMUNOLOGY　184　2010/04

    ISSN： 0022-1767

    eISSN： 1550-6606

  56. Synergistic up-regulation of cytokine encoding genes by CpG oligonucleotides plus poly (I:C)

    Lev Petrenko, Sven Klaschik, Hidekazu Shirota, Dennis M. Klinman

    CYTOKINE　43　(3)　284-284　2008/09

    DOI： 10.1016/j.cyto.2008.07.250 　

    ISSN： 1043-4666

Show all ︎Show first 5

Books and Other Publications 4

  1. Immunopotentiators in Modern Vaccines Second Edition

    Shirota H, Klinman DM

    Science & Technology Books, Life Science Academic Press/Elsevier.　2018

  2. Inflammation / From Molecular and Cellular Mechanisms to the Clinic"

    Klinman DM, Shirota H

    Wiley-VCH Verlag GmbH & Co. KGaA,　2017

  3. Nucleic Acids in Innate Immunity

    Klinman DM, Currie D, Fujimoto C, Gery I, Shirota H

    CRC Press　2008/05

  4. Vaccine Adjuvants and Delivery Systems

    Klinman DM, Currie D, Shirota H

    Manmohan Singh.　2006/11

Presentations 1

  1. 東北大学における未来型医療創生とがんゲノム医療への取り組み

    城田英和

    第16回日本臨床腫瘍学会学術集会　2018/07/20

Industrial Property Rights 1

  1. Compositions and Methods for the Treatment of Cancer

    Shirota H, Klinman DM

    Property Type: Patent

Research Projects 5

  1. 生体内の腫瘍細胞死が及ぼす腫瘍微小環境の変化

    城田 英和

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  2. The role of humoral immunity in tumor microenvironment

    Shirota Hidekazu

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2019/04/01 - 2022/03/31

    More details Close

    Various immune cells are recruited in the tumor microenvironment. It is well established that cellular immune responses, such as cytotoxic or suppressive activities, play an important role in regulating tumor growth and metastasis. However, the contribution of humoral immune responses against tumors is poorly understood. Fc receptors constitute critical elements for the up- or downregulation of immune responses through immune complexes. Here, we examined the potential role of the inhibitory Fc receptor, FcγRIIB, in tumor immunity using a mouse model. Our findings indicated that tumor-specific antibodies are induced in tumor-bearing mice and control tumor immunity. FcγRIIB deletion improved both cellular and humoral immunity against tumors and delayed tumor growth. These findings indicated that spontaneous antibodies against tumors create a suppressive tumor microenvironment through FcγRIIB signaling, thus suggesting an attractive therapeutic target for cancer immunotherapy.

  3. IL-4をターゲットとした癌免疫療法の開発 Competitive

    城田英和

    Offer Organization: 科研費

    System: 基盤研究(C)

    2016/04 - 2018/03

  4. Development of a novel anti-cancer immune therapy using the synthetic oligonucleotide containing poly-G motif

    Kobayashi Nobuaki, SHIBATA Yuji, SHINKAI Masaharu, KUDO Makoto, KANEKO Takeshi, SHIROTA Hidekazu

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Category: Grant-in-Aid for Young Scientists (B)

    Institution: Yokohama City University

    2014/04/01 - 2017/03/31

    More details Close

    Synthetic oligonucleotides (ODN) containing specific sequences have an immunomodulatory effect. We previously reported that a novel poly-G ODN has an anti-tumor immune effect in a tumor-bearing murine model. Here, we identified poly-G ODN-induced T cell proliferation and production of interferon-gamma through the enhancement of monocyte maturation in human mononuclear cells isolated from the peripheral blood or from the malignant pleural effusion of lung cancer patients. Poly-G ODN also induces the maturation of human monocytes into M1 macrophages through the phosphorylation of STAT1. This mechanism of poly-G ODN in humans is unique from that reported previously in mice for some ODNs containing three guanosines at the 3' tail. Further studies are ongoing to establish a novel anti-cancer immunotherapy for lung cancer with poly-G ODN.

  5. 腫瘍環境における慢性炎症・免疫細胞の機能解析と癌治療への応用 Competitive

    城田英和

    Offer Organization: 科研費

    System: 基盤研究(C)

    2013/04 - 2015/03