研究者詳細

顔写真

オオウチ　コウタ
大内　康太
Kota Ouchi
所属
大学院医学系研究科　医科学専攻　内科病態学講座（臨床腫瘍学分野）
職名
助教
学位

  • 医学博士 （東北大学）

研究キーワード 2

  • バイオマーカー

  • 大腸癌

研究分野 1

  • ライフサイエンス / 腫瘍診断、治療学 /

受賞 2

  1. Cancer Science Young Scientist Award

    2016年10月　日本癌学会　DNA methylation status as a biomarker of anti-EGFR treatment for metastatic colorectal cancer

  2. ESMO Asia 2015 トラベルグラント

    2015年11月　日本臨床腫瘍学会

論文 61

  1. Coexistence of TP53 and KRAS mutations identifies a molecular subset of biliary tract cancer with poor overall survival after first-line immunochemotherapy

    Shiori Ishikawa, Kota Ouchi, Shonosuke Wakayama, Shunsuke Oyamada, Tomoyuki Iwasaki, Ryunosuke Numakura, Yuya Yoshida, Sakura Taniguchi, Yuki Kasahara, Keigo Komine, Ken Saijo, Hidekazu Shirota, Hisato Kawakami

    European Journal of Cancer　242　116826-116826　2026年6月

    出版者・発行元： Elsevier BV

    DOI： 10.1016/j.ejca.2026.116826 　

    ISSN：0959-8049

  2. RAS/BRAF wild-type metastatic high-methylated colorectal cancer has gene expression patterns related to MSI-H and BRAF V600E mutant: a translational research. 国際誌

    Shonosuke Wakayama, Shin Takahashi, Kota Ouchi, Yasuhiro Sakamoto, Tadamichi Denda, Atsuo Takashima, Yoshito Komatsu, Masato Nakamura, Hisatsugu Ohori, Tatsuro Yamaguchi, Yoshimitsu Kobayashi, Hideo Baba, Masanori Kotake, Kenji Amagai, Hitoshi Kondo, Ken Shimada, Yasuhide Yamada, Atsushi Sato, Satoshi Yuki, Akira Okita, Keigo Komine, Mika Watanabe, Satoshi Morita, Chikashi Ishioka

    Scientific reports　2026年3月8日

    DOI： 10.1038/s41598-026-42033-w 　

  3. Attenuated Li–Fraumeni syndrome with TP53 p.R181H in a Japanese patient with metastatic rectal adenocarcinoma: a case report

    Yuki Kasahara, Masanobu Takahashi, Yoshifumi Kawamura, Yoko Aoki, Tetsuya Niihori, Maako Kawamura, Shinnosuke Yamamoto, Hidekazu Shirota, Ken Saijo, Hiroo Imai, Keigo Komine, Kota Ouchi, Sakura Taniguchi, Yuya Yoshida, Ryunosuke Numakura, Shiori Ishikawa, Tomoaki Shirakawa, Ryo Saito, Chikashi Ishioka, Hisato Kawakami

    Familial Cancer　25　(1)　2026年2月3日

    出版者・発行元： Springer Science and Business Media LLC

    DOI： 10.1007/s10689-026-00529-4 　

    eISSN：1573-7292

  4. Case Report: mTOR inhibitor treatment for epithelioid angiomyolipoma harboring biallelic TSC2 mutations. 国際誌

    Shiori Ishikawa, Kota Ouchi, Shonosuke Wakayama, Yuki Kasahara, Keigo Komine, Hiroo Imai, Ken Saijo, Yuto Yamazaki, Masanobu Takahashi, Hidekazu Shirota, Hisato Kawakami

    Frontiers in oncology　16　1735690-1735690　2026年

    DOI： 10.3389/fonc.2026.1735690 　

    詳細を見る 詳細を閉じる

    INTRODUCTION: Angiomyolipoma (AML) is a mesenchymal tumor composed of blood vessels, smooth muscle, and adipose tissue, and is generally considered benign. However, epithelioid angiomyolipoma (eAML) is a rare and aggressive variant with metastatic potential. Molecular characterization utilizing the tuberous sclerosis complex (TSC)-mTOR pathway is beneficial in advanced disease. This report describes the clinical course, histopathological findings, and molecular analysis of a patient with metastatic eAML. METHODS: A 59-year-old Japanese man with no personal or family history of tuberous sclerosis (TSC) was admitted to the hospital with gradually worsening back pain and initially diagnosed with clear cell renal cell carcinoma (ccRCC). He underwent nephrectomy, followed by hepatic recurrence treated with pazopanib and subsequent axitinib. Both were discontinued due to intolerance, and the two remaining liver metastases were surgically resected. Histopathological examination of the resected lesions revealed eAML. After several recurrences and resections, unresectable hepatic and pulmonary metastases eventually developed. RESULTS: Comprehensive genomic profiling (CGP) using the resected liver metastasis specimen identified two somatic TSC2 mutations: a frameshift mutation (p. P677fs*21; variant allele frequency [VAF] 0.0789) and a nonsense mutation (p. S1469*; VAF 0.0736), suggesting biallelic loss of TSC2. Based on these findings, everolimus, a mammalian/mechanistic target of rapamycin (mTOR) inhibitor, was recommended, which markedly reduced the size of the metastatic lesions and was continued for 24 months until disease progression without severe adverse events. DISCUSSION: This case suggests that CGP can help identify actionable alterations in eAML, such as TSC2 mutations, to guide personalized therapy with mTOR inhibitors.

  5. Characteristics of gut microbiota in high-methylated colorectal cancer.

    Tatsushi Saito, Hideaki Karasawa, Kota Ouchi, Tomoyuki Ono, Taiki Kajiwara, Atsushi Kohyama, Wakako Ikeda-Ohtsubo, Shinji Fukuda, Fumiyoshi Fujishima, Yohei Ozawa, Hideyuki Suzuki, Kazuhiro Watanabe, Chikashi Ishioka, Takashi Kamei, Shinobu Ohnuma, Takaaki Abe, Michiaki Unno

    International journal of clinical oncology　30　(9)　1805-1817　2025年9月

    DOI： 10.1007/s10147-025-02812-3 　

    詳細を見る 詳細を閉じる

    BACKGROUND: Epigenetic alterations, including DNA methylation, significantly contribute to colorectal cancer (CRC); the gut microbiota is also involved. However, studies on the possible role of microbiota in DNA methylation are limited. This study investigates the association between gut microbiota composition and high-methylated CRC (HMCC). METHODS: Fecal and tumor tissue samples were collected from 86 patients with sporadic CRC. HMCC was defined based on the methylation status of 16 CpG sites of tumor-derived genomic DNA. 16S rRNA gene sequencing was performed to reveal the composition of the gut microbiota. The load of Fusobacterium nucleatum (F. nucleatum) in tumor tissues was assessed using quantitative polymerase chain reaction (qPCR). RESULTS: HMCC was identified in 21 patients, whereas 65 were classified as having low-methylated CRC (LMCC). HMCC was significantly associated with proximal location, large diameter, undifferentiated histology, and high frequency of BRAF mutation. In gut microbial analyses, the relative abundances of 84 bacteria, including F. nucleatum, were significantly different between HMCC and LMCC. The load of F. nucleatum in CRC specimens was significantly correlated with its relative abundance in fecal samples and tended to be enriched in HMCC tissues. CONCLUSIONS: This study characterizes the gut microbiota profile in HMCC and suggests that bacteria, such as F. nucleatum, may contribute to HMCC pathogenesis through DNA methylation. Further studies are needed to determine whether the microbiome acts as a promoter or bystander in HMCC development.

  6. Plasma Lysophosphatidylcholine Levels Correlate with Prognosis and Immunotherapy Response in Squamous Cell Carcinoma

    Tomoyuki Iwasaki, Hidekazu Shirota, Eiji Hishinuma, Shinpei Kawaoka, Naomi Matsukawa, Yuki Kasahara, Kota Ouchi, Hiroo Imai, Ken Saijo, Keigo Komine, Masanobu Takahashi, Chikashi Ishioka, Seizo Koshiba, Hisato Kawakami

    International Journal of Molecular Sciences　26　(15)　7528-7528　2025年8月4日

    出版者・発行元： MDPI AG

    DOI： 10.3390/ijms26157528 　

    eISSN：1422-0067

    詳細を見る 詳細を閉じる

    Cancer is a systemic disease rather than a localized pathology and is characterized by widespread effects, including whole-body exhaustion and chronic inflammation. A thorough understanding of cancer pathophysiology requires a systemic approach that accounts for the complex interactions between cancer cells and host tissues. To explore these dynamics, we employed a comprehensive metabolomic analysis of plasma samples from patients with either esophageal or head and neck squamous cell carcinoma (SCC). Plasma samples from 149 patients were metabolically profiled and correlated with clinical data. Among the metabolites identified, lysophosphatidylcholine (LPC) emerged as the sole biomarker strongly correlated with prognosis. A significant reduction in plasma LPC levels was linked to poorer overall survival. Plasma LPC levels demonstrated minimal correlation with patient-specific factors, such as tumor size and general condition, but showed significant association with the response to immune checkpoint inhibitor therapy. Proteomic and cytokine analyses revealed that low plasma LPC levels reflected systemic chronic inflammation, characterized by high levels of inflammatory proteins, the cytokines interleukin-6 and tumor necrosis factor-α, and coagulation-related proteins. These findings indicate that plasma LPC levels may be used as reliable biomarkers for predicting prognosis and evaluating the efficacy of immunotherapy in patients with SCC.

  7. Dynamic predictive power of TP53 signatures in breast cancer prognosis: Pre- and post-neoadjuvant chemotherapy insights. 国際誌

    Keiju Sasaki, Shin Takahashi, Kota Ouchi, Hidekazu Shirota, Nobuaki Sato, Kouji Kaneko, Norikazu Masuda, Fumiyoshi Fujishima, Satoko Sato, Chikashi Ishioka

    Translational oncology　56　102398-102398　2025年6月

    DOI： 10.1016/j.tranon.2025.102398 　

    詳細を見る 詳細を閉じる

    BACKGROUND: The TP53 signature determined using a biopsy specimen before neoadjuvant chemotherapy (pre-NAC biopsy specimens) predicts NAC response and prognosis in breast cancer. We aimed to compare the clinical utility of the TP53 signature determined using pre-NAC biopsy specimens and surgical specimens after NAC (post-NAC surgical specimens). METHODS: This observational cohort study included patients with paired pre-NAC biopsy and post-NAC surgical specimens, analyzing the association between the TP53 signature from each specimen and prognosis (UMIN000042055). RESULTS: Pre-NAC biopsy specimens classified 71 patients into those having a TP53 mutant signature (pre-mt, n = 47) and wild-type signature (pre-wt, n = 24), with the same for post-NAC surgical specimens (post-mt, n = 16 and post-wt, n = 55). Among the 47 pre-mt patients, 31 became post-wt (pre-mt/post-wt), whereas 16 remained post-mt (pre-mt/post-mt). All pre-wt patients remained post-wt (pre-wt/post-wt). Recurrence-free survival (RFS) was significantly shorter in the pre-mt group than in the pre-wt group, although no significant difference was observed between the post-mt and post-wt groups. Change in the TP53 signature following NAC did not affect predictive ability of the TP53 signature determined using pre-NAC biopsy specimens. CONCLUSIONS: The TP53 signature status should be determined using pre-NAC biopsy specimens.

  8. A retrospective study of pembrolizumab plus chemotherapy for head and neck cancer patients: influence of response in combination phase on subsequent maintenance phase. 国際誌

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

    Discover oncology　16　(1)　479-479　2025年4月7日

    DOI： 10.1007/s12672-025-02256-1 　

    詳細を見る 詳細を閉じる

    BACKGROUND: Pembrolizumab plus chemotherapy is considered one of the standard treatment regimens for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The regimen comprises up to 6 cycles of pembrolizumab-chemotherapy combination phase and subsequent pembrolizumab maintenance phase. Pembrolizumab-chemotherapy combination confers high response rate, creating favorable conditions for pembrolizumab maintenance phase. This study examined the influence of response in the combination phase on the efficacy in subsequent maintenance phase. METHODS: We retrospectively reviewed the medical records of patients with R/M HNSCC who received pembrolizumab plus chemotherapy as a first-line regimen at Tohoku University Hospital, Sendai, Japan. Progression-free survival (PFS) was analyzed when it was divided into the combination and maintenance phases. RESULTS: A total of 44 patients were enrolled. The best overall response was observed in the combination phase in all patients, and the overall response rate was 46.3%. The median PFS was 5.8 months (95% CI: 4.9-7.1). PFS differed significantly according to the response. When analyzed separately, the PFS only in the maintenance phase differed depending on the response of partial response (PR) or stable disease (SD). There was no difference in the number of chemotherapy cycles between patients with PR and SD. Univariate and multivariate analyses showed that the response in the combination phase was significantly associated with PFS in the maintenance phase. CONCLUSION: In the pembrolizumab plus chemotherapy regimen for patients with R/M HNSCC, the response in the combination phase may be associated with PFS in the maintenance phase.

  9. Coexisting germline variants of MLH1 and MSH6 in a patient with Lynch syndrome who had uterine and ovarian cancer. 国際誌

    Sho Umegaki, Masanobu Takahashi, Junko Hasegawa-Minato, Maako Kawamura, Sakura Taniguchi, Keigo Komine, Hideki Tokunaga, Kota Ouchi, Hiroo Imai, Ken Saijo, Hidekazu Shirota, Fumiyoshi Fujishima, Muneaki Shimada, Yoko Aoki, Chikashi Ishioka

    International cancer conference journal　14　(2)　171-176　2025年4月

    DOI： 10.1007/s13691-025-00753-2 　

    詳細を見る 詳細を閉じる

    Lynch syndrome is an autosomal dominant disorder caused by a heterozygous pathogenic germline variant in mismatch repair (MMR) genes including MLH1, MSH2, MSH6, PMS2, and EPCAM. This disease often causes a familial cluster of patients with malignant tumors. In this report, we describe a 37-year-old woman who presented with endometrioid carcinoma in the ovary and uterine corpus associated with Lynch syndrome. She carried two germline pathogenic variants, a recurrently reported MLH1 c.2250C > G (p.Tyr750*) and a previously unreported MSH6 c.2385del (p.Ile795Metfs*15). The tumor cells showed microsatellite instability. Immunohistochemistry for the endometrial tumor showed decreased MLH1 expression, loss of PMS2 expression, retained MSH2 expression, and loss of MSH6 expression, which suggests that both variants impair each protein stability and thus cause MMR deficiency. Whether these variants were inherited from her parents or occurred de novo was unknown. The tumor cells had somatic variants BRCA1 c.1016del and BRCA2 c.36dupT that might be due to secondary mutation by MMR deficiency. The use of an immune checkpoint inhibitor pembrolizumab resulted in durable partial response of metastatic lung tumors. This case reminds clinicians of the rare possibility of multiple germline variants in MMR genes in individuals with Lynch syndrome.

  10. 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年2月28日

    DOI： 10.1007/s10147-025-02724-2 　

    詳細を見る 詳細を閉じる

    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.

  11. Outcomes of Chemotherapy for Advanced Esophageal Squamous Cell Carcinoma: A Study Using Real-World Data.

    Tomoyuki Iwasaki, Masanobu Takahashi, Kota Ouchi, Keigo Komine, Yuki Kasahara, Noriko Takenaga, Shuto Kodera, Shonosuke Wakayama, Ryunosuke Numakura, Reio Ueta, Keiju Sasaki, Yuya Yoshida, Sakura Taniguchi, Hiroo Imai, Ken Saijo, Hidekazu Shirota, Yusuke Taniyama, Keiichi Jingu, Takashi Kamei, Chikashi Ishioka

    The Tohoku journal of experimental medicine　2025年2月13日

    DOI： 10.1620/tjem.2025.J021 　

  12. Entrapment of a Guidewire Caused by the Chiari Network During Implantation of a Central Venous Port: A Case Report

    Shonosuke Wakayama, Rika Saito, Kota Ouchi, Yuya Yoshida, Hiromitsu Tannai, Hirofumi Watanabe, Shuto Kodera, Tomoyuki Iwasaki, Yoshifumi Kawamura, Masanobu Takahashi, Chikashi Ishioka, Hisato Kawakami

    Internal Medicine　2025年

    出版者・発行元： Japanese Society of Internal Medicine

    DOI： 10.2169/internalmedicine.6256-25 　

    ISSN：0918-2918

    eISSN：1349-7235

  13. Pretreatment neutrophil-lymphocyte ratio as a prognostic factor in recurrent/metastatic head and neck cancer treated with pembrolizumab. 国際誌

    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年11月16日

    DOI： 10.1038/s41598-024-79130-7 　

    詳細を見る 詳細を閉じる

    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.

  14. [Epigenome Diagnosis of Cancer-Focusing on Genome-Wide DNA Methylation Diagnosis of Colorectal Cancer for Predicting Sensitivity of Anti-EGFR Antibody Treatment].

    Chikashi Ishioka, Kota Ouchi, Shonosuke Wakayama, Shin Takahashi

    Gan to kagaku ryoho. Cancer & chemotherapy　51　(11)　1089-1094　2024年11月

    ISSN：0385-0684

    詳細を見る 詳細を閉じる

    Epigenetic regulation mechanisms such as DNA methylation and histone acetylation are important for controlling various biological phenomena by regulating gene expression at the genome level. They are reversible systems that change depending on environmental factors. Epigenetic abnormalities are associated with the onset of various diseases, including developmental and aging abnormalities, neurological disorders, and malignant tumors. Aberrant DNA methylation is an important epigenetic change in the development and progression of colorectal cancer. DNA methylation in tumor tissues occurs mainly in CpG islands in the promoter regions of genes and inactivates gene functions by negatively suppressing transcription. CpG island methylator phenotype(CIMP)is an important carcinogenic mechanism of colorectal cancer related to DNA methylation and is involved in approximately 20% of all colorectal cancers. CIMP is generally judged to be positive when a certain percentage or more of the marker gene set is methylated, and many CIMP markers have been reported so far. However, no established marker has been set to classify colorectal cancer by genome-wide DNA methylation. We developed a new method to assess genome-wide DNA methylation status and obtained pharmaceutical approval as a new in vitro diagnostic drug to predict sensitivity to anti-EGFR antibody drugs in colorectal cancer.

  15. Nivolumab-induced Thrombotic Thrombocytopenic Purpura in Patients with Gastric Tube Cancer.

    Yuya Yoshida, Sakura Toriyabe, Hiroo Imai, Keiju Sasaki, Yuki Kasahara, Kota Ouchi, Ken Saijo, Koichi Onodera, Chikashi Ishioka

    Internal medicine (Tokyo, Japan)　63　(19)　2667-2671　2024年10月1日

    DOI： 10.2169/internalmedicine.2931-23 　

    詳細を見る 詳細を閉じる

    Recently, immune checkpoint inhibitors (ICIs) have been used to treat several cancer types. ICIs have been reported to cause a wide variety of immune-related adverse events, including endocrine, neurologic, gastrointestinal, and cutaneous disorders. Thrombotic thrombocytopenic purpura (TTP) is an autoimmune hematologic disorder characterized by the presence of autoantibodies against a disintegrin and metalloprotease with thrombospondin-1, member 13. Several previous cases of TTP were thought to have been caused by ICI treatment. We herein report a rare case of TTP that developed after long-term treatment with an ICI (nivolumab) for gastric tube cancer.

  16. Specific cancer types and prognosis in patients with variations in the <scp>KEAP1</scp>‐<scp>NRF2</scp> system: A retrospective cohort study 査読有り

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

    Cancer Science　2024年9月26日

    DOI： 10.1111/cas.16355 　

    ISSN：1347-9032 1349-7006

    詳細を見る 詳細を閉じる

    <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>

  17. 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年6月13日

    DOI： 10.2169/internalmedicine.3373-23 　

    詳細を見る 詳細を閉じる

    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.

  18. 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. 国際誌

    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年6月11日

    DOI： 10.1007/s00384-024-04659-y 　

    詳細を見る 詳細を閉じる

    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.

  19. Chylous Ascites Associated with Advanced Pancreatic Cancer That Improved with Appropriate Treatment: A Case Report. 国際誌

    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年3月12日

    DOI： 10.3390/curroncol31030112 　

    詳細を見る 詳細を閉じる

    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.

  20. Erratum for Nivolumab-induced Thrombotic Thrombocytopenic Purpura in Patients with Gastric Tube Cancer.

    Yuya Yoshida, Sakura Toriyabe, Hiroo Imai, Keiju Sasaki, Yuki Kasahara, Kota Ouchi, Ken Saijo, Koichi Onodera, Chikashi Ishioka

    Internal medicine (Tokyo, Japan)　63　(24)　3407-3407　2024年

    DOI： 10.2169/internalmedicine.E003-24 　

  21. FOLFIRI Chemotherapy for Patients With Metastatic Urachal Carcinoma. 国際誌

    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年12月

    DOI： 10.21873/anticanres.16775 　

    詳細を見る 詳細を閉じる

    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.

  22. Comparison of efficacy and safety between carboplatin-etoposide and cisplatin-etoposide combination therapy in patients with advanced neuroendocrine carcinoma, retrospective study. 国際誌

    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年10月30日

    DOI： 10.1159/000534747 　

    詳細を見る 詳細を閉じる

    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.

  23. 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年9月14日

    出版者・発行元： S. Karger AG

    DOI： 10.1159/000533860 　

    ISSN：0030-2414

    eISSN：1423-0232

    詳細を見る 詳細を閉じる

    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.

  24. TP53 Gain-of-Function Mutation is a Poor Prognostic Factor in High-Methylated Metastatic Colorectal Cancer. 国際誌

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

    Clinical colorectal cancer　2023年6月7日

    DOI： 10.1016/j.clcc.2023.06.001 　

    詳細を見る 詳細を閉じる

    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.

  25. Phase II study of biweekly cetuximab plus mFOLFOX6 or mFOLFIRI as second-line treatment for metastatic colorectal cancer and exploratory analysis of associations between DNA methylation status and the efficacy of the anti-EGFR antibody: T-CORE1201

    Shin Takahashi, Kota Ouchi, Yasuhiro Sakamoto, Takahiro Mori, Hideki Shimodaira, Masahiro Takahashi, Hisatsugu Ohori, Chieko Kudo, Yoshikazu Takahashi, Hiroo Imai, Shoko Akiyama, Masanobu Takahashi, Takeshi Suto, Yasuko Murakawa, Takayuki Oishi, Hideki Isobe, Yoshinari Okada, Sadayuki Kawai, Takashi Yoshioka, Toshihiko Sato, Yoshiaki Shindo, Shunsuke Sugiyama, Keigo Komine, Natsuko Chiba, Akira Okita, Takuhiro Yamaguchi, Chikashi Ishioka

    Journal of Gastrointestinal Oncology　14　(2)　676-691　2023年4月

    出版者・発行元： AME Publishing Company

    DOI： 10.21037/jgo-22-862 　

    ISSN：2078-6891

    eISSN：2219-679X

  26. Different impacts of TP53 mutations on cell cycle-related gene expression among cancer types. 国際誌

    Keiju Sasaki, Shin Takahashi, Kota Ouchi, Yasufumi Otsuki, Shonosuke Wakayama, Chikashi Ishioka

    Scientific reports　13　(1)　4868-4868　2023年3月24日

    DOI： 10.1038/s41598-023-32092-8 　

    詳細を見る 詳細を閉じる

    Functional properties caused by TP53 mutations are involved in cancer development and progression. Although most of the mutations lose normal p53 functions, some of them, gain-of-function (GOF) mutations, exhibiting novel oncogenic functions. No reports have analyzed the impact of TP53 mutations on the gene expression profile of the p53 signaling pathway across cancer types. This study is a cross-cancer type analysis of the effects of TP53 mutations on gene expression. A hierarchical cluster analysis of the expression profile of the p53 signaling pathway classified 21 cancer types into two clusters (A1 and A2). Changes in the expression of cell cycle-related genes and MKI67 by TP53 mutations were greater in cluster A1 than in cluster A2. There was no distinct difference in the effects between GOF and non-GOF mutations on the gene expression profile of the p53 signaling pathway.

  27. Depth of response may predict clinical outcome in patients with recurrent/metastatic head and neck cancer treated with pembrolizumab-containing regimens. 国際誌

    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年

    DOI： 10.3389/fonc.2023.1230731 　

    詳細を見る 詳細を閉じる

    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.

  28. 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年8月30日

    出版者・発行元： S. Karger AG

    DOI： 10.1159/000526018 　

    eISSN：1662-6575

    詳細を見る 詳細を閉じる

    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.

  29. Altered gene expression due to aberrant DNA methylation correlates with responsiveness to anti-EGFR antibody treatment. 国際誌

    Yasufumi Otsuki, Kota Ouchi, Shin Takahashi, Keiju Sasaki, Yasuhiro Sakamoto, Akira Okita, Chikashi Ishioka

    Cancer science　2022年4月11日

    DOI： 10.1111/cas.15367 　

    詳細を見る 詳細を閉じる

    The cetuximab gene expression signature and DNA methylation status of colorectal cancer (CRC) are predictive of the therapeutic effects of anti-epidermal growth factor receptor (EGFR) antibody therapy. Since DNA methylation is a means of regulating gene expression, it may play an important role in the expression of cetuximab signature genes. This study aims to determine the effects of aberrant DNA methylation on the regulation of cetuximab signature gene expression. Comprehensive DNA methylation and gene expression data were retrieved from CRC patients in three tumor tissue (TT) cohorts and three normal colorectal mucosa/tumor tissue paired (NCM-TT) cohorts. Of the 231 cetuximab signature genes, 57 exhibited an inverse correlation between the methylation of promoter CpG sites and gene expression level in multiple cohorts. About two-thirds of the promoter CpG sites associated with the 57 genes exhibited this correlation. In all 57 gene promoter regions, the methylation levels in NCMs did not differ according to comparisons based on cetuximab signature or DNA methylation status classification of matched TTs. Thus, the altered expression of 57 genes was caused by aberrant DNA methylation during carcinogenesis. Analysis of the association between cetuximab signature or DNA methylation status and progression-free survival (PFS) of anti-EGFR antibody agents in the same cohort showed that DNA methylation status was most associated with PFS. In conclusion, we found that aberrant DNA methylation regulates specific gene expression in cetuximab signature during carcinogenesis, suggesting that it is one of the important determinants of sensitivity to anti-EGFR antibody agents.

  30. A modified MethyLight assay predicts the clinical outcomes of anti-epidermal growth factor receptor treatment in metastatic colorectal cancer. 国際誌

    Kota Ouchi, Shin Takahashi, Akira Okita, Yasuhiro Sakamoto, Osamu Muto, Kenji Amagai, Takaho Okada, Hisatsugu Ohori, Eiji Shinozaki, Chikashi Ishioka

    Cancer science　113　(3)　1057-1068　2022年3月

    DOI： 10.1111/cas.15252 　

    詳細を見る 詳細を閉じる

    DNA methylation status correlates with clinical outcomes of anti-epidermal growth factor receptor (EGFR) treatment. There is a strong need to develop a simple assay for measuring DNA methylation status for the clinical application of drug selection based on it. In this study, we collected data from 186 patients with metastatic colorectal cancer (mCRC) who had previously received anti-EGFR treatment. We modified MethyLite to develop a novel assay to classify patients as having highly methylated colorectal cancer (HMCC) or low-methylated colorectal cancer (LMCC) based on the methylation status of 16 CpG sites of tumor-derived genomic DNA in the development cohort (n = 30). Clinical outcomes were then compared between the HMCC and LMCC groups in the validation cohort (n = 156). The results showed that HMCC had a significantly worse response rate (4.2% vs 33.3%; P = .004), progression-free survival (median: 2.5 vs 6.6 mo, P < .001, hazard ratio [HR] = 0.22), and overall survival (median: 5.6 vs 15.5 mo, P < .001, HR = 0.23) than did LMCC in patients with RAS wild-type mCRC who were refractory or intolerable to oxaliplatin- and irinotecan-based chemotherapy (n = 101). The DNA methylation status was an independent predictive factor and a more accurate biomarker than was the primary site of anti-EGFR treatment. In conclusion, our novel DNA methylation measurement assay based on MethyLight was simple and useful, suggesting its implementation as a complementary diagnostic tool in a clinical setting.

  31. 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年10月

    出版者・発行元： (一社)日本癌治療学会

  32. 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

    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年9月

    DOI： 10.1007/s00280-021-04277-3 　

    ISSN：0344-5704

    eISSN：1432-0843

  33. Advanced colorectal cancer subtypes (aCRCS) help select oxaliplatin-based or irinotecan-based therapy for colorectal cancer. 国際誌

    Shin Takahashi, Yasuhiro Sakamoto, Tadamichi Denda, Atsuo Takashima, Yoshito Komatsu, Masato Nakamura, Hisatsugu Ohori, Tatsuro Yamaguchi, Yoshimitsu Kobayashi, Hideo Baba, Masanori Kotake, Kenji Amagai, Hitoshi Kondo, Ken Shimada, Atsushi Sato, Satoshi Yuki, Akira Okita, Kota Ouchi, Keigo Komine, Mika Watanabe, Satoshi Morita, Chikashi Ishioka

    Cancer science　112　(4)　1567-1578　2021年4月

    DOI： 10.1111/cas.14841 　

    詳細を見る 詳細を閉じる

    Oxaliplatin (OX) and irinotecan (IRI) are used as key drugs for the first-line treatment of metastatic colorectal cancer (mCRC). However, no biomarkers have been identified to decide which of the drugs is initially used. In this translational research (TR) of the TRICOLORE trial, the advanced colorectal cancer subtype (aCRCS) was analyzed as a potential biomarker for the selection of OX or IRI. We collected 335 (68.8%) formalin-fixed, paraffin-embedded (FFPE) primary tumor specimens from 487 patients registered in the TRICOLORE trial and performed direct sequencing and immunohistochemical staining of CRC-related genes, comprehensive gene-expression analysis, and genome-wide methylation analysis. The progression-free survival (PFS) of the IRI group was significantly better compared with the OX group in BRAF wild-type (WT), PTEN-positive, and aCRCS A1 patients. Among the molecular factors, aCRCS were only associated with the PFS of OX and IRI groups. The PFS of the IRI group was significantly better compared with the OX group in aCRCS A1 + B1 (hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.41-0.82; P = .0023). In contrast, the OX group had better PFS compared with the IRI group in aCRCS B2, although this was not statistically significant (HR = 1.66; 95% CI = 0.94-2.96; P = .083). Nearly half of patients with mCRC (46.8%, aCRCS A1 + B1) respond well to IRI, while only about 18.5% (aCRCS B2) of patients with mCRC responded well to OX. In conclusion, the aCRCS might be a predictive factor for the clinical outcomes of OX-based and IRI-based therapies.

  34. 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年3月

    出版者・発行元： (一社)日本胃癌学会

  35. Phase ii study of the reuse of trastuzumab with docetaxel beyond progression after first-line treatment in second-line treatment for unresectable, metastatic gastric cancer (T-core1203)

    Masanobu Takahashi, Yasuhiro Sakamoto, Kazunori Otsuka, Mariko Kanbe, Hisatsugu Ohori, Yoshiaki Shindo, Hiroshi Honda, Ken Saijo, Kota Ouchi, Yasuko Murakawa, Hidekazu Takahashi, Sadayuki Kawai, Yuichi Tanaka, Takuhiro Yamaguchi, Hideki Shimodaira, Takashi Yoshioka, Chikashi Ishioka

    Tohoku Journal of Experimental Medicine　254　(1)　49-55　2021年

    DOI： 10.1620/tjem.254.49 　

    ISSN：0040-8727

    eISSN：1349-3329

  36. 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年4月

    DOI： 10.1007/s10147-019-01592-x 　

    詳細を見る 詳細を閉じる

    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.

  37. Antibiotics Improve the Treatment Efficacy of Oxaliplatin-Based but Not Irinotecan-Based Therapy in Advanced Colorectal Cancer Patients. 国際誌

    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年

    DOI： 10.1155/2020/1701326 　

    詳細を見る 詳細を閉じる

    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.

  38. 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年10月

    出版者・発行元： (一社)日本癌治療学会

  39. 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年10月

    出版者・発行元： (一社)日本癌治療学会

  40. 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年10月

    出版者・発行元： (一社)日本癌治療学会

  41. 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年10月

    出版者・発行元： (一社)日本癌治療学会

  42. Advanced Invasive Extramammary Paget's Disease Concomitant with Cecal Cancer Possessing Rare Variant of TP53 Single Nucleotide Polymorphism. 査読有り

    Kambayashi Y, Fujimura T, Ohuchi K, Tono H, Ishida Y, Otsuka A, Aiba S

    Case reports in oncology　12　(3)　855-860　2019年9月

    DOI： 10.1159/000504339 　

  43. Therapeutic Benefits of Ipilimumab among Japanese Patients with Nivolumab-Refractory Mucosal Melanoma: A Case Series Study. 査読有り

    Saijo K, Imai H, Ouchi K, Okada Y, Sato Y, Komine K, Takahashi M, Takahashi S, Shirota H, Takahashi M, Ishioka C

    The Tohoku journal of experimental medicine　248　(1)　37-43　2019年5月

    DOI： 10.1620/tjem.248.37 　

    ISSN：0040-8727

  44. 胃癌に合併したDIC治療の後方視的検討

    佐藤 悠子, 大内 康太, 高橋 信, たら澤 邦男, 藤森 研司, 石岡 千加史

    日本内科学会雑誌　108　(Suppl.)　209-209　2019年2月

    出版者・発行元： (一社)日本内科学会

    ISSN：0021-5384

    eISSN：1883-2083

  45. 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年2月

    出版者・発行元： (一社)日本内科学会

    ISSN：0021-5384

    eISSN：1883-2083

  46. 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年10月

    出版者・発行元： (一社)日本癌治療学会

  47. Retrospective analysis on the clinical outcomes of recombinant human soluble thrombomodulin for disseminated intravascular coagulation syndrome associated with solid tumors. 査読有り

    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

    International journal of clinical oncology　23　(4)　790-798　2018年8月

    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. 査読有り

    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

    The Tohoku journal of experimental medicine　245　(2)　123-129　2018年6月

    DOI： 10.1620/tjem.245.123 　

    ISSN：0040-8727

    eISSN：1349-3329

  49. Consensus molecular subtypes classification of colorectal cancer as a predictive factor for chemotherapeutic efficacy against metastatic colorectal cancer. 国際誌 査読有り

    Akira Okita, Shin Takahashi, Kota Ouchi, Masahiro Inoue, Mika Watanabe, Mareyuki Endo, Hiroshi Honda, Yasuhide Yamada, Chikashi Ishioka

    Oncotarget　9　(27)　18698-18711　2018年4月10日

    DOI： 10.18632/oncotarget.24617 　

    詳細を見る 詳細を閉じる

    The consensus molecular subtypes (CMS) classification is one of the most robust colorectal cancer (CRC) classifications based on comprehensive gene expression profiles. This study aimed to clarify whether the CMS is a predictive factor for therapeutic effects of standard chemotherapies for metastatic CRC (mCRC). We retrospectively enrolled 193 patients with mCRCs, and using comprehensive gene expression data, classified them into 4 subtypes: CMS1-CMS4. The associations between the subtypes and treatment outcomes were analyzed. Regarding first-line chemotherapy, irinotecan (IRI)-based chemotherapy was significantly superior to oxaliplatin (OX)-based chemotherapy for progression-free survival (PFS; hazard ratio [HR] = 0.31, 95% confidence interval [CI] 0.13-0.64) and overall survival (OS; HR = 0.45, 95% CI 0.19-0.99) in CMS4. Regarding the anti-epidermal growth factor receptor (anti-EGFR) therapy, CMS1 showed particularly worse PFS (HR = 2.50, 95% CI 1.31-4.39) and OS (HR = 4.23, 95% CI 1.83-9.04), and CMS2 showed particularly good PFS (HR = 0.67, 95% CI 0.44-1.01) and OS (HR = 0.49, 95% CI 0.27-0.87) compared with the other subtypes. The biological characteristics of CMS may influence the efficacy of chemotherapy. CMS might be a new predictive factor for the efficacy of chemotherapy against mCRCs.

  50. The consensus molecular subtypes of colorectal cancer as a predictive factor for chemotherapies against metastatic colorectal cancer. 査読有り

    Okita Akira, Takahashi Shin, Ouchi Kota, Inoue Masahiro, Yamada Yasuhide, Ishioka Chikashi

    JOURNAL OF CLINICAL ONCOLOGY　36　(4)　2018年2月1日

    ISSN：0732-183X

  51. Development of a molecular target agent and a biomarker for advanced colorectal cancer 査読有り

    Ishioka Chikashi, Saijo Ken, Takahashi Shin, Ouchi Kota, Imai Hiroo, Takahashi Shin

    CANCER SCIENCE　109　141　2018年1月

    ISSN：1349-7006

  52. The Consensus Molecular Subtypes is a predictive biomarker for anti-EGFR antibody effect in metastatic colorectal cancer 査読有り

    Okita Akira, Takahashi Shin, Ouchi Kota, Yamada Yasuhide, Takahashi Masanobu, Ishioka Chikashi

    CANCER SCIENCE　109　673　2018年1月

    ISSN：1349-7006

  53. Predictive factors for the efficacy of the second taxane treatment in patients with advanced cancer. 国際誌 査読有り

    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年

    DOI： 10.2147/CMAR.S170948 　

  54. microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer 査読有り

    Hidekazu Takahashi, Masanobu Takahashi, Shinobu Ohnuma, Michiaki Unno, Yuki Yoshino, Kota Ouchi, Shin Takahashi, Yasuhide Yamada, Hideki Shimodaira, Chikashi Ishioka

    BMC CANCER　17　(1)　723　2017年11月

    DOI： 10.1186/s12885-017-3739-x 　

    ISSN：1471-2407

    eISSN：1471-2407

  55. The G8 screening tool enhances prognostic value to ECOG performance status in elderly cancer patients: A retrospective, single institutional study 査読有り

    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年6月

    DOI： 10.1371/journal.pone.0179694 　

    ISSN：1932-6203

  56. CpG island methylator phenotype is associated with the efficacy of sequential oxaliplatin- and irinotecan-based chemotherapy and EGFR-related gene mutation in Japanese patients with metastatic colorectal cancer 査読有り

    Xiaofei Zhang, Hideki Shimodaira, Hiroshi Soeda, Keigo Komine, Hidekazu Takahashi, Kota Ouchi, Masahiro Inoue, Masanobu Takahashi, Shin Takahashi, Chikashi Ishioka

    International Journal of Clinical Oncology　21　(6)　1091-1101　2016年12月

    DOI： 10.1007/s10147-016-1017-6 　

    ISSN：1341-9625

    eISSN：1437-7772

  57. DNA methylation status as a biomarker of anti-epidermal growth factor receptor treatment for metastatic colorectal cancer 査読有り

    Kota Ouchi, Shin Takahashi, Yasuhide Yamada, Shingo Tsuji, Kenji Tatsuno, Hidekazu Takahashi, Naoki Takahashi, Masanobu Takahashi, Hideki Shimodaira, Hiroyuki Aburatani, Chikashi Ishioka

    CANCER SCIENCE　106　(12)　1722-1729　2015年12月

    DOI： 10.1111/cas.12827 　

    ISSN：1349-7006

  58. DNA methylation status as a biomarker of anti-epidermal growth factor receptor treatment for metastatic colorectal cancer. 査読有り

    Ouchi K, Takahashi S, Yamada Y, Tsuji S, Tatsuno K, Takahashi H, Takahashi N, Takahashi M, Shimodaira H, Aburatani H, Ishioka C

    Cancer science　106　(12)　1722-1729　2015年12月

    DOI： 10.1111/cas.12827 　

    ISSN：1347-9032

  59. Development of the new biomarker of colorectal cancer using the comprehensive molecular analyses 査読有り

    Takahashi Shin, Kota Ouchi, Ishioka Chikashi

    ANNALS OF ONCOLOGY　26　42　2015年11月

    ISSN：0923-7534

  60. DNA methylation profile to predict clinical outcome of anti-EGFR treatment in metastatic colorectal cancer. 査読有り

    Ouchi Kota, Takahashi Shin, Yamada Yasuhide, Tsuji Shingo, Tatsuno Kenji, Takahashi Hidekazu, Takahashi Naoki, Takahashi Masanobu, Shimodaira Hideki, Aburatani Hiroyuki, Ishioka Chikashi

    JOURNAL OF CLINICAL ONCOLOGY　33　(15)　2015年5月20日

    ISSN：0732-183X

  61. Acute exacerbation of paraneoplastic neurological syndrome after massive tumor lysis of neuroendocrine carcinoma by chemoradiotherapy 査読有り

    Yoshino Y, Akiyama S, Ouchi K, Oishi T, Takahashi H, Lee J, Takahashi S, Shimodaira H, Kato S, Ishioka C

    International Cancer Conference Journal　2　(4)　247-250　2013年10月

︎全件表示 ︎最初の5件までを表示

MISC 32

  1. がん遺伝子パネル検査の選択と治療実践の現状と課題

    小峰啓吾, 城田英和, 川村真亜子, 笠原佑記, 大内康太, 今井源, 西條憲, 宮内栄作, 新妻秀剛, 多田寛, 島田宗昭, 新堀哲也, 青木洋子, 古川徹, 高橋雅信, 高橋雅信, 石岡千加史, 石岡千加史

    日本遺伝性腫瘍学会学術集会プログラム・抄録集　30th　2024年

  2. 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

    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年

  3. 皮下埋込型中心静脈ポート造設手技中にガイドワイヤーがキアリ網に捕捉された一例

    若山祥之介, 若山祥之介, 斎藤里佳, 斎藤里佳, 大内康太, 大内康太, 丹内啓允, 渡邊裕文, 小寺修仁, 小寺修仁, 岩崎智行, 岩崎智行, 川村佳史, 川村佳史, 高橋雅信, 高橋雅信, 高橋雅信, 石岡千加史, 石岡千加史, 石岡千加史

    日本腫瘍循環器学会学術集会抄録集(Web)　6th　2023年

  4. 再発または遠隔転移を有する頭頸部癌に対するnivolumabの有効性および安全性に関する検討

    梅垣翔, 高橋信, 平出桜, 沖田啓, 笠原佑記, 大内康太, 西條憲, 高橋昌宏, 高橋雅信, 石岡千加史

    日本内科学会雑誌　107　(Suppl.)　272-272　2018年2月20日

    出版者・発行元： (一社)日本内科学会

    ISSN： 0021-5384

    eISSN： 1883-2083

  5. 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年2月20日

    出版者・発行元： (一社)日本内科学会

    ISSN： 0021-5384

  6. 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年10月

    出版者・発行元： (一社)日本癌治療学会

  7. 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年10月

    出版者・発行元： (一社)日本癌治療学会

  8. HER2陽性進行・再発胃癌に対するtrastuzumab併用化学療法に関する検討

    梅垣 翔, 沖田 啓, 今井 源, 高橋 秀和, 大堀 久詔, 大内 康太, 蒲生 真紀夫, 山田 英晴, 笠原 佑記, 近松 園子, 高橋 昌宏, 下平 秀樹, 石岡 千加史

    日本癌治療学会学術集会抄録集　55回　P84-5　2017年10月

    出版者・発行元： (一社)日本癌治療学会

  9. がん分子標的治療薬の分子基盤と臨床応用 進行大腸癌の新しい分子標的薬とバイオマーカーの開発

    石岡 千加史, 西條 憲, 高橋 信, 大内 康太, 今井 源, 高橋 雅信

    日本癌学会総会記事　76回　S5-6　2017年9月

    出版者・発行元： 日本癌学会

    ISSN： 0546-0476

  10. Consensus Molecular Subtypes(CMS)は抗EGFR抗体薬の治療効果予測因子となる

    沖田 啓, 高橋 信, 大内 康太, 山田 康秀, 高橋 雅信, 石岡 千加史

    日本癌学会総会記事　76回　P-2212　2017年9月

    出版者・発行元： 日本癌学会

    ISSN： 0546-0476

  11. 消化器癌及び希少がんの骨転移患者の骨関連事象予防に関するデノスマブとゾレドロン酸の効果比較

    近松 園子, 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 雅信, 石岡 千加史

    日本内科学会雑誌　106　(Suppl.)　236-236　2017年2月

    出版者・発行元： (一社)日本内科学会

    ISSN： 0021-5384

  12. HER2陽性胃癌に対するTrastuzumab併用化学療法に関する検討

    沖田 啓, 今井 源, 高橋 秀和, 高橋 昌宏, 大内 康太, 山田 英晴, 笠原 佑記, 近松 園子, 下平 秀樹, 石岡 千加史

    日本内科学会雑誌　106　(Suppl.)　237-237　2017年2月

    出版者・発行元： (一社)日本内科学会

    ISSN： 0021-5384

  13. 消化器癌及び希少がんの骨転移患者の骨関連事象予防に関するデノスマブとゾレドロン酸の効果比較

    近松 園子, 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 雅信, 石岡 千加史

    日本内科学会雑誌　106　(Suppl.)　236-236　2017年2月

    出版者・発行元： (一社)日本内科学会

    ISSN： 0021-5384

  14. HER2陽性胃癌に対するTrastuzumab併用化学療法に関する検討

    沖田 啓, 今井 源, 高橋 秀和, 高橋 昌宏, 大内 康太, 山田 英晴, 笠原 佑記, 近松 園子, 下平 秀樹, 石岡 千加史

    日本内科学会雑誌　106　(Suppl.)　237-237　2017年2月

    出版者・発行元： (一社)日本内科学会

    ISSN： 0021-5384

  15. Consensus molecular subtypes(CMS)に基づく,進行・再発大腸癌に対する最適な化学療法の検討

    沖田啓, 高橋信, 大内康太, 山田英晴, 笠原佑記, 近松園子, 高橋秀和, 高橋雅信, 下平秀樹, 石岡千加史

    日本臨床腫瘍学会学術集会(CD-ROM)　15th　ROMBUNNO.O3‐5‐4　2017年

  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年

  17. HER2陽性進行・再発胃癌に対するtrastuzumab併用XP療法またはSP療法の有効性と安全性に関する後方視的検討

    梅垣翔, 梅垣翔, 沖田啓, 沖田啓, 今井源, 今井源, 高橋秀和, 大堀久詔, 大内康太, 大内康太, 大内康太, 蒲生真紀夫, 山田英晴, 山田英晴, 笠原佑記, 笠原佑記, 近松園子, 近松園子, 高橋昌宏, 高橋昌宏, 下平秀樹, 下平秀樹, 石岡千加史, 石岡千加史

    日本癌治療学会学術集会(Web)　55th　ROMBUNNO.P84‐5 (WEB ONLY)　2017年

  18. 消化器癌領域における最新の医療研究開発 大腸がん治療におけるエピジェネティックバイオマーカー

    高橋 信, 大内 康太, 石岡 千加史

    日本癌学会総会記事　75回　SST2-5　2016年10月

    出版者・発行元： 日本癌学会

    ISSN： 0546-0476

  19. 膵臓 膵がんに対する化学療法の検討 FOLFIRINOX療法およびGEM+nabPTX療法導入後の進行膵癌患者の生存期間の後ろ向き解析

    近松 園子, 高橋 昌宏, 山田 英晴, 沖田 啓, 小林 輝大, 佐藤 悠子, 大内 康太, 岡田 佳也, 小峰 啓吾, 西條 憲, 今井 源, 高橋 信, 高橋 雅信, 下平 秀樹, 石岡 千加史

    日本癌治療学会学術集会抄録集　54回　WS2-4　2016年10月

    出版者・発行元： (一社)日本癌治療学会

  20. 消化器癌領域における最新の医療研究開発 大腸がん治療におけるエピジェネティックバイオマーカー

    高橋 信, 大内 康太, 石岡 千加史

    日本癌学会総会記事　75回　SST2-5　2016年10月

    出版者・発行元： 日本癌学会

    ISSN： 0546-0476

  21. 膵臓 膵がんに対する化学療法の検討 FOLFIRINOX療法およびGEM+nabPTX療法導入後の進行膵癌患者の生存期間の後ろ向き解析

    近松 園子, 高橋 昌宏, 山田 英晴, 沖田 啓, 小林 輝大, 佐藤 悠子, 大内 康太, 岡田 佳也, 小峰 啓吾, 西條 憲, 今井 源, 高橋 信, 高橋 雅信, 下平 秀樹, 石岡 千加史

    日本癌治療学会学術集会抄録集　54回　WS2-4　2016年10月

    出版者・発行元： (一社)日本癌治療学会

  22. 【がん分子標的治療の副作用と対策】 副作用別対策 消化器毒性

    大内 康太, 高橋 信, 石岡 千加史

    がん分子標的治療　13　(1)　53-59　2015年4月

    出版者・発行元： (株)メディカルレビュー社

    ISSN： 1347-6955

  23. 東北大学病院腫瘍内科においてエベロリムスを投与した8例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, 大内康太, 高橋秀和, 今井源, 高橋昌宏, 森隆弘, 加藤俊介, 下平秀樹, 石岡千加史

    日本臨床腫瘍学会学術集会(CD-ROM)　13th　ROMBUNNO.P1-8-56　2015年

  24. FFPE検体を使用した全エクソン解析

    大内康太, 高橋信, 辰野健二, 林玲匡, 山本尚吾, 上田宏生, 井上正広, 仲野弘美, 油谷浩幸, 石岡千加史

    日本がん分子標的治療学会学術集会プログラム・抄録集　18th　63　2014年5月29日

  25. FFPE組織を用いた全エクソン解析(Whole-exome sequencing using formalin-fixed paraffin embedded tissue)

    大内 康太, 高橋 信, 辰野 健二, 林 玲匡, 山本 尚吾, 上田 宏生, 井上 正広, 仲野 弘美, 油谷 浩幸, 石岡 千加史

    日本癌学会総会記事　72回　401-401　2013年10月

    出版者・発行元： 日本癌学会

    ISSN： 0546-0476

  26. 網羅的遺伝子発現解析による大腸がんの新規バイオマーカー開発

    高橋信, 井上正広, 大内康太, 添田大司, 下平秀樹, 三浦康, 渡辺みか, 加藤俊介, 石岡千加史

    日本がん分子標的治療学会学術集会プログラム・抄録集　17th　130　2013年5月31日

  27. 軟部肉腫に対するADM+IFM併用療法の治療成績に関する後方視的検討

    西條 憲, 大内 康太, 高橋 秀和, 角道 祐一, 高橋 信, 高橋 雅信, 添田 大司, 李 仁, 加藤 俊介, 石岡 千加史

    日本内科学会雑誌　102　(Suppl.)　196-196　2013年2月

    出版者・発行元： (一社)日本内科学会

    ISSN： 0021-5384

  28. 神経線維腫症1型に併発した悪性末梢神経鞘腫瘍に対し化学療法を行った3例

    下平 秀樹, 西條 憲, 大内 康太, 高橋 秀和, 吉野 優樹, 李 仁, 佐藤 悠子, 塩野 雅俊, 加藤 俊介, 石岡 千加史

    日本内科学会雑誌　102　(Suppl.)　243-243　2013年2月

    出版者・発行元： (一社)日本内科学会

    ISSN： 0021-5384

  29. マイクロサテライト不安定性陽性の転移再発大腸癌の臨床的特徴の検討

    高橋秀和, 高橋雅信, 井上正広, 添田大司, 大内康太, ZHANG Xiaofei, 高橋信, 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)　11th　ROMBUNNO.P3-065　2013年

  30. 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)の有効性に関する後方視的解析

    大内 康太, 高橋 信, 下平 秀樹, 角道 祐一, 秋山 聖子, 吉田 こず恵, 塩野 雅俊, 加藤 俊介, 石岡 千加史

    日本内科学会雑誌　101　(Suppl.)　160-160　2012年2月

    出版者・発行元： (一社)日本内科学会

    ISSN： 0021-5384

  31. 悪性腫瘍に対する塩酸イリノテカンを含む薬物療法におけるUGT1A1遺伝子多型と有害事象発現との関連に対する後方視的検討

    LEE Jin, 秋山聖子, 大内康太, 大石隆之, 齋藤菜穂子, 高橋秀和, 加藤俊介, 角道祐一, 下平秀樹, 森隆弘, 高橋信, 大堀久詔, 吉田こず恵, 石岡千加史

    日本臨床腫瘍学会学術集会プログラム・抄録集　10th　164-165　2012年

  32. 進行再発大腸癌においてセツキシマブ不応後にパニツムマブを施行した治療成績

    李 仁, 加藤 俊介, 高橋 昌宏, 高橋 秀和, 大内 康太, 吉野 優樹, 大石 隆之, 斎藤 菜穂子, 杉山 俊輔, 岡田 佳也, 小峰 啓吾, 西條 憲, 河合 貞幸, 井上 正広, 今井 源, 塩野 雅俊, 吉田 こず恵, 秋山 聖子, 高橋 信, 角道 祐一, 下平 秀樹, 森 隆弘, 石岡 千加史

    東北医学雑誌　123　(2)　210-210　2011年12月

    出版者・発行元： 東北医学会

    ISSN： 0040-8700

︎全件表示 ︎最初の5件までを表示

産業財産権 1

  1. 大腸癌に対する薬物療法の感受性を予測する方法

    石岡 千加史, 高橋 信, 大内 康太, 下平 秀樹, 油谷 浩幸

    産業財産権の種類: 特許権

共同研究・競争的資金等の研究課題 5

  1. DNAメチル化状態に基づいた頭頸部癌薬物療法のバイオマーカー開発

    西條 憲, 大内 康太

    2024年4月1日 ～ 2027年3月31日

  2. 進行胃癌のDIC併発に関連する遺伝子発現異常の網羅的探索研究

    大内 康太

    2020年4月1日 ～ 2023年3月31日

    詳細を見る 詳細を閉じる

    2020年度の実績報告書に記載の通り、網羅的遺伝子発現解析の対象症例として、東北大学病院腫瘍内科及び大崎市民病院腫瘍内科において胃癌の治療経過中にDICを併発し、かつDICの原因疾患が感染症ではなく腫瘍であると考えられた症例15例および治療経過中にDICを併発しなかった症例15例からなる合計30例を選定し、臨床データおよび腫瘍組織を収集した。 バイオアナライザを用いて収集された検体から抽出されたRNAのQCを行い、マイクロアレイの適否を判断した結果、DIC併発群で13例、DIC併発無し群で12例が適合基準を満たした。 上記25例について、マイクロアレイ（Whole Human Genome Oligo Microarray kit: Agilent Technologies社）を用いて網羅的遺伝子発現データを取得した。 はじめにDICを併発した群13例とDICを併発しなかった群12例との間で有意に発現状態が異なる遺伝子群を探索した。発現データが取得可能であったプローブは合計41,093個であり、シグナル値が低いプローブは解析対象から除外した結果、29,423個のプローブが解析対象となった。これらのプローブについて2群間の有意差の検定（Mann-Whitney unpaired）を行い、多重性の検定（Benjamini-Hochberg法)および有意基準（補正p値 <0.05）でフィルタリングを行った結果、2群間で有意差のある遺伝子は抽出されなかった。 続いて網羅的遺伝子発現データを取得した25例全体で教師なしクラスタリング解析を行った結果、DIC併発ありの症例は、大きく分けて2群に分かれることが明らかとなり、1群は遺伝子発現の変動が非常に大きい特徴的な発現パターンを呈しており（DIC_1）、もう1群はDIC併発なしの症例に類似した発現パターンを示した（DIC_2）。

  3. DNA高メチル化型大腸癌の発症病態の解明と診断・治療法開発に関する研究

    石岡 千加史, 高橋 雅信, 高橋 信, 大内 康太

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Scientific Research (B)

    研究機関：Tohoku University

    2019年4月1日 ～ 2022年3月31日

    詳細を見る 詳細を閉じる

    切除不能進行・再発大腸癌(mCRC)の治療モデルの提案を目的とした。抗生物質がオキザリプラチン(Ox)を含む治療の効果を改善することからマイクロビオームが治療効果に関連することが示唆された。遺伝子発現プロファイルaCRCSはmCRCにおけるOxまたはイリノテカン・ベースの治療感受性の予測に有用であった。miR-193a-3pはBRAF変異大腸がん細胞においてMAPK関連経路の活性化抑制によりBRAFおよびMEK阻害薬の効果を増強することを明らかにした。セツキシマブ・シグネチャー(CMS)の231遺伝子のうち57遺伝子の発現は、プロモーター領域のDNAメチル化により調節されていることを見出した。

  4. 大腸癌の治療感受性を予測する新規バイオマーカーの探索

    大内 康太

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Early-Career Scientists

    研究機関：Tohoku University

    2018年4月1日 ～ 2020年3月31日

    詳細を見る 詳細を閉じる

    HMCC群における正常大腸粘膜と腫瘍組織との間でメチル化状態が変化している355の遺伝子に関連するCpG領域を抽出した。抽出されたCpG領域について、139例のデータセットでHMCC群とLMCC群とを比較すると、HMCC群のみで特異的にメチル化されている領域を含む遺伝子が62個抽出された。これらの遺伝子のいずれかに生じた、メチル化状態の変化による遺伝子発現異常が抗EGFR抗体薬の治療感受性の差を生じているものと考えられた。139例のデータセットを用いて、62個の遺伝子についてHMCC群とLMCC群とで有意に発現状態に差のある遺伝子を探索したが、両群で有意差を示す遺伝子は同定されなかった。

  5. 高DNAメチル化型大腸癌の抗EGFR抗体薬耐性克服に関する研究

    石岡 千加史, 高橋 雅信, 高橋 信, 大内 康太, 沖田 啓, 小林 輝大

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Scientific Research (B)

    研究機関：Tohoku University

    2015年4月1日 ～ 2018年3月31日

    詳細を見る 詳細を閉じる

    本研究の目的は、高DNAメチル化型大腸癌の抗EGFR抗体薬治療耐性の分子機構を明らかにすること、及びこの治療耐性を克服するための方策を探索することにある。網羅的遺伝子発現解析の結果、我々は、特定のサブグループが切除不能進行再発大腸癌の1次治療の治療効果や2次治療以降の抗EGFR抗体薬の治療感受性と相関することを明らかにした。網羅的miRNA発現解析の結果、我々はmiR-193a-3pがBRAF変異腫瘍と強く相関すること同定し、miR-193a-3pの低発現が抗EGFR抗体薬の治療抵抗性と関連することを明らかにした。今後、さらに研究を発展させる予定である。