Faculty Profiles - SHIGEYASU Kunitoshi

Papers - SHIGEYASU Kunitoshi

Division display 21 - 40 of about 92 ／ All the affair displays >>

ADAR1 is a promising risk stratification biomarker of remnant liver recurrence after hepatic metastasectomy for colorectal cancer. International journal

Nanako Hata, Kunitoshi Shigeyasu, Yuzo Umeda, Shuya Yano, Sho Takeda, Kazuhiro Yoshida, Tomokazu Fuji, Ryuichi Yoshida, Kazuya Yasui, Hibiki Umeda, Toshiaki Takahashi, Yoshitaka Kondo, Hiroyuki Kishimoto, Yoshiko Mori, Fuminori Teraishi, Hideki Yamamoto, Hiroyuki Michiue, Keiichiro Nakamura, Hiroshi Tazawa, Toshiyoshi Fujiwara

Scientific reports 13 ( 1 ) 2078 - 2078 2023.2

Language：English Publishing type：Research paper (scientific journal)

Adenosine-to-inosine RNA editing is a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family. It has been discovered recently as an epigenetic modification dysregulated in human cancers. However, the clinical significance of RNA editing in patients with liver metastasis from colorectal cancer (CRC) remains unclear. The current study aimed to systematically and comprehensively investigate the significance of adenosine deaminase acting on RNA 1 (ADAR1) expression status in 83 liver metastatic tissue samples collected from 36 patients with CRC. The ADAR1 expression level was significantly elevated in liver metastatic tissue samples obtained from patients with right-sided, synchronous, or RAS mutant-type CRC. ADAR1-high liver metastasis was significantly correlated with remnant liver recurrence after hepatic metastasectomy. A high ADAR1 expression was a predictive factor of remnant liver recurrence (area under the curve = 0.72). Results showed that the ADAR1 expression level could be a clinically relevant predictive indicator of remnant liver recurrence. Patients with liver metastases who have a high ADAR1 expression requires adjuvant chemotherapy after hepatic metastasectomy.

DOI： 10.1038/s41598-023-29397-z

A Case Report of Non-typical Annular Pancreas Diagnosed during Laparoscopic Gastric Surgery.

Toshiaki Takahashi, Yoshihiko Kakiuchi, Satoru Kikuch, Shinji Kuroda, Sho Takeda, Kunitoshi Shigeyasu, Yoshitaka Kondo, Fuminori Teraishi, Shunsuke Kagawa, Toshiyoshi Fujiwara

Acta medica Okayama 77 ( 1 ) 91 - 95 2023.2

Language：English

An annular pancreas is a rare anomaly of the pancreas, defined as pancreatic tissue that totally or partly encircles the duodenum, usually the descending portion. A 76-year-old man who was diagnosed with gastric cancer cT3N0M0 Stage IIB underwent laparoscopic distal gastrectomy with D2 lymph node dissection. Intraoperatively, the dorsal half of the duodenal bulb was seen to be half surrounded by the pancreas, and a non-typical annular pancreas was diagnosed. Because of the risk to the pancreas, it was considered impossible to perform anastomosis by a linear stapler as in the usual laparoscopic procedure. Therefore, we performed laparoscopically assisted distal gastrectomy and Billroth-I reconstruction using a circular stapler, and the surgery was completed without difficulties. His postoperative course was good despite the development of a pancreatic fistula, which was an International Study Group for Pancreas Fistula biochemical leak. Some APs can be diagnosed preoperatively, but the rarer subtypes such as ours are more difficult to visualize on imaging. In gastrectomy, it is both oncologically important and technically challenging to perform lymph node dissection around the pancreas. In this case with an especially proximal pancreas, a circular stapler was considered better suited for gastroduodenal anastomosis and required a broader field than that afforded by laparoscopy. A case of non-typical annular pancreas diagnosed during laparoscopic gastric surgery is described.

DOI： 10.18926/AMO/64368

RNA editing is a valuable biomarker for predicting carcinogenesis in ulcerative colitis. International journal

Kazutaka Takahashi, Kunitoshi Shigeyasu, Yoshitaka Kondo, Kazuyoshi Gotoh, Shuya Yano, Yuzo Umeda, Toshihiro Inokuchi, Caiming Xu, Kazuhiro Yoshida, Hibiki Umeda, Toshiaki Takahashi, Sho Takeda, Ryuichi Yoshida, Fuminori Teraishi, Hiroyuki Kishimoto, Yoshiko Mori, Kazuhiro Noma, Yoshinaga Okugawa, Sakiko Hiraoka, Hiroyuki Michiue, Hiroshi Tazawa, Osamu Matsushita, Ajay Goel, Toshiyoshi Fujiwara

Journal of Crohn's & colitis 17 ( 5 ) 754 - 766 2022.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND AIMS: Ulcerative colitis (UC) can develop colitis-associated colorectal neoplasm (CAN). Adenine-to-inosine RNA editing, which is regulated by adenosine deaminase acting on RNA (ADAR), induces the posttranscriptional modification of critical oncogenes, including antizyme inhibitor 1 (AZIN1), leading to colorectal carcinogenesis. Therefore, we hypothesized that ADAR1 might be involved in the development of CAN in UC. METHODS: We systematically analyzed a cohort of 139 UC cases (40 acute phase, 73 remission phase, 26 CAN). The degree of inflammation was evaluated using the Mayo endoscopic score (MES). RESULTS: The type 1 IFN-related inflammation pathway was upregulated in the rectum of active UC, rectum of UC-CAN, and tumor site of UC-CAN patients. ADAR1 expression was upregulated in the entire colon of CAN cases, while it was down-regulated in non-CAN MES0 cases. ADAR1 expression in the rectum predicted the development of CAN better than p53 or β-catenin, with an area under the curve of 0.93. The high expression of ADAR1 and high AZIN1 RNA editing in UC was triggered by type 1 IFN stimulation from UC-specific microbiomes, such as Fusobacterium in vitro analyses. The induction of AZIN1 RNA editing by ADAR1, whose expression is promoted by Fusobacterium, may induce carcinogenesis in UC. CONCLUSIONS: The risk of CAN can be evaluated by assessing ADAR1 expression in the rectum of MES0 UC patients, freeing UC patients from unnecessary colonoscopy and reducing their physical burden. RNA editing may be involved in UC carcinogenesis, and may be used to facilitate the prevention and treatment of CAN in UC.

DOI： 10.1093/ecco-jcc/jjac186

Dysregulated DNA methylation in the pathogenesis of Fabry disease. International journal

Jin-Song Shen, Uthra Balaji, Kunitoshi Shigeyasu, Yoshinaga Okugawa, Siamak Jabbarzadeh-Tabrizi, Taniqua S Day, Erland Arning, John Marshall, Seng H Cheng, Jinghua Gu, Raphael Schiffmann, Teodoro Bottiglieri, Ajay Goel

Molecular genetics and metabolism reports 33 100919 - 100919 2022.12

Language：English Publishing type：Research paper (scientific journal)

Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A and subsequent accumulation of glycosphingolipids with terminal α-D-galactosyl residues. The molecular process through which this abnormal metabolism of glycosphingolipids causes multisystem dysfunction in Fabry disease is not fully understood. We sought to determine whether dysregulated DNA methylation plays a role in the development of this disease. In the present study, using isogenic cellular models derived from Fabry patient endothelial cells, we tested whether manipulation of α-galactosidase A activity and glycosphingolipid metabolism affects DNA methylation. Bisulfite pyrosequencing revealed that changes in α-galactosidase A activity were associated with significantly altered DNA methylation in the androgen receptor promoter, and this effect was highly CpG loci-specific. Methylation array studies showed that α-galactosidase A activity and glycosphingolipid levels were associated with differential methylation of numerous CpG sites throughout the genome. We identified 15 signaling pathways that may be susceptible to methylation alterations in Fabry disease. By incorporating RNA sequencing data, we identified 21 genes that have both differential mRNA expression and methylation. Upregulated expression of collagen type IV alpha 1 and alpha 2 genes correlated with decreased methylation of these two genes. Methionine levels were elevated in Fabry patient cells and Fabry mouse tissues, suggesting that a perturbed methionine cycle contributes to the observed dysregulated methylation patterns. In conclusion, this study provides evidence that α-galactosidase A deficiency and glycosphingolipid storage may affect DNA methylation homeostasis and highlights the importance of epigenetics in the pathogenesis of Fabry disease and, possibly, of other lysosomal storage disorders.

DOI： 10.1016/j.ymgmr.2022.100919

Clinical features of biliary tract cancer in Japanese individuals with Lynch syndrome. International journal

Nobuhiko Kanaya, Hideki Aoki, Toshiaki Morito, Fumitaka Taniguchi, Kunitoshi Shigeyasu, Chieko Tamura, Kokichi Sugano, Kiwamu Akagi, Hideyuki Ishida, Kohji Tanakaya

Journal of gastrointestinal oncology 13 ( 5 ) 2532 - 2538 2022.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Biliary tract cancer (BTC) is a Lynch syndrome (LS)-associated cancer with a high mortality rate. This study aimed to clarify the clinical features of BTC in individuals with LS and to discuss its management. METHODS: We obtained data from genetically verified Japanese individuals with LS who were diagnosed at a single institution, between January 2003 and April 2021. Moreover, 21 individuals with sporadic BTC (n=15) and LS associated BTC (n=6) underwent microsatellite instability (MSI) testing. RESULTS: Among 92 individuals with LS, 6 individuals with MLH1 variants developed BTCs (10 lesions, male/female, 2:1). The median age at diagnosis of initial BTC was 69 years (range, 34-78 years). Histological examination revealed a predominance of differentiated adenocarcinoma (89%). Then, 2 individuals had multiple BTCs. All available 7 BTC lesions showed high-frequency of microsatellite instability (MSI-H). MLH1 carriers showed a 7.2% cumulative risk of BTC development at an age of 70 years. Five of the six individuals died of BTC. CONCLUSIONS: MSI analysis could facilitate LS identification in individuals with BTC. Surveillance for BTC should be considered for MLH1 carriers in Japan.

DOI： 10.21037/jgo-22-165

RNA editing facilitates the enhanced production of neoantigens during the simultaneous administration of oxaliplatin and radiotherapy in colorectal cancer. International journal

Yasuhiro Komatsu, Kunitoshi Shigeyasu, Shuya Yano, Sho Takeda, Kazutaka Takahashi, Nanako Hata, Hibiki Umeda, Kazuhiro Yoshida, Yoshiko Mori, Kazuya Yasui, Ryuichi Yoshida, Yoshitaka Kondo, Hiroyuki Kishimoto, Fuminori Teraishi, Yuzo Umeda, Shunsuke Kagawa, Hiroyuki Michiue, Hiroshi Tazawa, Ajay Goel, Toshiyoshi Fujiwara

Scientific reports 12 ( 1 ) 13540 - 13540 2022.8

Language：English Publishing type：Research paper (scientific journal)

Most cases of colorectal cancers (CRCs) are microsatellite stable (MSS), which frequently demonstrate lower response rates to immune checkpoint inhibitors (ICIs). RNA editing produces neoantigens by altering amino acid sequences. In this study, RNA editing was induced artificially by chemoradiation therapy (CRT) to generate neoantigens in MSS CRCs. Altogether, 543 CRC specimens were systematically analyzed, and the expression pattern of ADAR1 was investigated. In vitro and in vivo experiments were also performed. The RNA editing enzyme ADAR1 was upregulated in microsatellite instability-high CRCs, leading to their high affinity for ICIs. Although ADAR1 expression was low in MSS CRC, CRT including oxaliplatin (OX) treatment upregulated RNA editing levels by inducing ADAR1. Immunohistochemistry analyses showed the upregulation of ADAR1 in patients with CRC treated with CAPOX (capecitabine + OX) radiation therapy relative to ADAR1 expression in patients with CRC treated only by surgery (p < 0.001). Compared with other regimens, CRT with OX effectively induced RNA editing in MSS CRC cell lines (HT29 and Caco2, p < 0.001) via the induction of type 1 interferon-triggered ADAR1 expression. CRT with OX promoted the RNA editing of cyclin I, a neoantigen candidate. Neoantigens can be artificially induced by RNA editing via an OX-CRT regimen. CRT can promote proteomic diversity via RNA editing.

DOI： 10.1038/s41598-022-17773-0

ADAR1 and AZIN1 RNA editing function as an oncogene and contributes to immortalization in endometrial cancer. International journal

Keiichiro Nakamura, Kunitoshi Shigeyasu, Kazuhiro Okamoto, Hirofumi Matsuoka, Hisashi Masuyama

Gynecologic oncology 166 ( 2 ) 326 - 333 2022.6

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Adenosine-to-inosine (A-to-I) RNA editing is a recently described epigenetic modification, which is believed to constitute a key oncogenic mechanism in human cancers. However, its functional role and clinical significance in endometrial cancer (EC) remain unclear. METHODS: Adenosine Deaminase family Acting on RNA1 (ADAR1) expression and Antizyme inhibitor 1 (AZIN1) RNA editing were examined to clarify the correlation with clinicopathological parameters and prognosis in EC patients. The biological functions and inhibitory effects of ADAR1 knockdown were investigated in JHUCS-1 and TU-ECS-1 EC cell lines. RESULTS: ADAR1 showed significant association with worse histology (P = 0.006), and lymph vascular space involvement (P = 0.049) in EC. The level of AZIN1 RNA editing was also significantly associated with worse histology (P = 0.012). ADAR1 expression was significantly correlated with AZIN1 RNA editing level (R = 0.729, R2 = 0.547, P < 0.001). Multivariate analysis indicated that higher ADAR1 expression along with AZIN1 RNA editing is an independent predictor of prognosis in EC patients (P = 0.015). Knockdown of ADAR1 led to increased MDA-5, RIG-I, PKR, and IRF-7 expression, which in turn resulted in increased levels of Bak and apoptosis in EC cells. CONCLUSIONS: High ADAR1 expression along with AZIN1 RNA editing could be a predictor of worse prognosis in EC. ADAR1 could be a potential therapeutic target in EC patients.

DOI： 10.1016/j.ygyno.2022.05.026

Tumor-targeted fluorescence labeling systems for cancer diagnosis and treatment. International journal

Hiroshi Tazawa, Kunitoshi Shigeyasu, Kazuhiro Noma, Shunsuke Kagawa, Fuminori Sakurai, Hiroyuki Mizuguchi, Hisataka Kobayashi, Takeshi Imamura, Toshiyoshi Fujiwara

Cancer science 113 ( 6 ) 1919 - 1929 2022.6

Language：English Publishing type：Research paper (scientific journal)

Conventional imaging techniques are available for clinical identification of tumor sites. However, detecting metastatic tumor cells that are spreading from primary tumor sites using conventional imaging techniques remains difficult. In contrast, fluorescence-based labeling systems are useful tools for detecting tumor cells at the single-cell level in cancer research. The ability to detect fluorescent-labeled tumor cells enables investigations of the biodistribution of tumor cells for the diagnosis and treatment of cancer. For example, the presence of fluorescent tumor cells in the peripheral blood of cancer patients is a predictive biomarker for early diagnosis of distant metastasis. The elimination of fluorescent tumor cells without damaging normal tissues is ideal for minimally invasive treatment of cancer. To capture fluorescent tumor cells within normal tissues, however, tumor-specific activated target molecules are needed. This review focuses on recent advances in tumor-targeted fluorescence labeling systems, in which indirect reporter labeling using tumor-specific promoters is applied to fluorescence labeling of tumor cells for the diagnosis and treatment of cancer. Telomerase promoter-dependent fluorescence labeling using replication-competent viral vectors produces fluorescent proteins that can be used to detect and eliminate telomerase-positive tumor cells. Tissue-specific promoter-dependent fluorescence labeling enables identification of specific tumor cells. Vimentin promoter-dependent fluorescence labeling is a useful tool for identifying tumor cells that undergo epithelial-mesenchymal transition (EMT). The evaluation of tumor cells undergoing EMT is important for accurately assessing metastatic potential. Thus, tumor-targeted fluorescence labeling systems represent novel platforms that enable the capture of tumor cells for the diagnosis and treatment of cancer.

DOI： 10.1111/cas.15369

Regulatory T cells induce a suppressive immune milieu and promote lymph node metastasis in intrahepatic cholangiocarcinoma. International journal

Daisuke Konishi, Yuzo Umeda, Kazuhiro Yoshida, Kunitoshi Shigeyasu, Shuya Yano, Tomohiro Toji, Sho Takeda, Ryuichi Yoshida, Kazuya Yasui, Tomokazu Fuji, Kazuyuki Matsumoto, Hiroyuki Kishimoto, Hiroyuki Michiue, Fuminori Teraishi, Hironari Kato, Hiroshi Tazawa, Hiroyuki Yanai, Takahito Yagi, Ajay Goel, Toshiyoshi Fujiwara

British journal of cancer 127 ( 4 ) 757 - 765 2022.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Emerging evidence indicates that immunogenicity plays an important role in intrahepatic cholangiocarcinoma (ICC). Herein, we systematically evaluated the clinical relevance of immunogenicity in ICC. METHODS: Highly immunogenic ICCs identified in the public dataset and the Cancer Immunome Atlas (TCIA) were assessed to determine the prognostic impact of immunogenicity in ICC and key components after curative resection. We also investigated the clinical relevance of the immune milieu in ICC. RESULTS: Using the Gene Expression Omnibus dataset 89749 and TCIA, we identified CD8+/forkhead box P3 (FoxP3)+ tumour-infiltrating lymphocytes (TILs), T-cell immunoglobulin and mucin domain 3 (TIM-3) and human leukocyte antigen-A (HLA-A) in highly immunogenic ICCs. Immunohistochemical analysis of the in-house cohort showed that intratumoral FoxP3+ TILs correlated with CD8+ TILs (P = 0.045, Fisher's exact test) and that high FoxP3+/CD8+ ratio (FCR) was an important marker for poor survival (P < 0.001, log-rank test). Furthermore, the FCR was higher in tumour-free lymph nodes in ICCs with lymph node metastases than in those without lymph node metastases (P = 0.003, Mann-Whitney U test). CONCLUSIONS: FCR should be considered an important biomarker that represents the immune environment of ICC based on its potentially important role in tumour progression, especially lymph node metastasis.

DOI： 10.1038/s41416-022-01838-y

Anorectal leiomyoma with GLUT1 overexpression mimicking malignancy on FDG-PET/CT. International journal

Fuminori Teraishi, Kunitoshi Shigeyasu, Shunsuke Kagawa, Toshiyoshi Fujiwara

Journal of surgical case reports 2022 ( 5 ) rjac101 2022.5

Language：English

A 43-year-old female underwent pelvic magnetic resonance imaging for uterine myoma that incidentally revealed a 4.6 × 2.8 cm soft tissue mass in the anorectal region. Rectal endoscopy showed a submucosal tumor just above the anal canal. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed an anorectal tumor with very high FDG uptake. Aspiration cytology and needle biopsy were inconclusive, and the patient underwent trans-perineal tumor resection. The excised tumor was a 4.6 × 3.5 × 2.7 cm gray-white bifurcated nodular tumor. Light microscopy revealed fenestrated growth of poorly dysmorphic short spindle-shaped cells with eosinophilic sporophytes. Immunohistochemical staining was positive for αSMA and desmin, negative for CD117 (KIT) and S100, and the patient was diagnosed with benign leiomyoma. Tumor cells were also positive for glucose transporter-1 (GLUT1) immunohistochemically. It is important to keep in mind that FDG-PET/CT may show false-positive results even in benign anal leiomyoma for various reasons, including GLUT1 overexpression.

DOI： 10.1093/jscr/rjac101

Association between Advanced T Stage and Thick Rectus Abdominis Muscle and Outlet Obstruction and High-Output Stoma after Ileostomy in Patients with Rectal Cancer

Yasuhiro Komatsu, Kunitoshi Shigeyasu, Sho Takeda, Yoshiko Mori, Kazutaka Takahashi, Nanako Hata, Kokichi Miyamoto, Hibiki Umeda, Yoshihiko Kakiuchi, Satoru Kikuchi, Shuya Yano, Shinji Kuroda, Yoshitaka Kondo, Hiroyuki Kishimoto, Fuminori Teraishi, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

International Surgery 106 ( 3 ) 102 - 111 2022

Publishing type：Research paper (scientific journal)

Objective: This study aimed to identify factors associated with outlet obstruction and high-output stoma (HOS) after ileostomy creation. Summary of background data: Ileostomy creation is effective in preventing leakage among patients undergoing low anterior resection for rectal cancer. However, major complications such as outlet obstruction and HOS can occur after surgery. Moreover, these complications cannot be prevented. Methods: This retrospective study included 34 patients with rectal cancer who underwent low anterior resection and ileostomy creation at Okayama University Hospital from January 2015 to December 2018. Then, the risk factors associated with outlet obstruction and HOS were analyzed. Results: Of 34 patients, 7 (21%) experienced outlet obstruction. In a multivariate logistic regression analysis, advanced T stage (P ¼ 0.10), ileostomy with a short horizontal diameter (P ¼ 0.01), and thick rectus abdominis (RA) muscle (P ¼ 0.0005) were considered independent risk factors for outlet obstruction. There was a significant correlation between outlet obstruction and HOS (P ¼ 0.03). Meanwhile, the independent risk factors of HOS were advanced T stage (P ¼ 0.03) and thick RA muscle (P ¼ 0.04). Conclusions: Thick RA muscle and advanced T stage were the common risk factors of outlet obstruction and HOS. Therefore, in high-risk patients, these complications can be prevented by choosing an appropriate ileostomy location according to RA muscle thickness and by preventing tubing into the ileostomy.

DOI： 10.9738/INTSURG-D-21-00012.1

A Case of a Transwoman with Colorectal Cancer after Flap Vaginoplasty

Shiho Watanabe, Fuminori Teraishi, Sari Fujimoto, Toshiyuki Watanabe, Sho Takeda, Shuhei Narita, Koya Yamashita, Kunitoshi Shigeyasu, Shunsuke Kagawa, Yuzaburo Namba, Yoshihiro Kimata

Journal of Plastic and Reconstructive Surgery 2022

Immuno-hyperthermia effected by antibody-conjugated nanoparticles selectively targets and eradicates individual cancer cells. International journal

Tetsuya Kagawa, Yuki Matsumi, Hiromichi Aono, Toshiaki Ohara, Hiroshi Tazawa, Kunitoshi Shigeyasu, Shuya Yano, Sho Takeda, Yasuhiro Komatsu, Robert M Hoffman, Toshiyoshi Fujiwara, Hiroyuki Kishimoto

Cell cycle (Georgetown, Tex.) 20 ( 13 ) 1 - 11 2021.6

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS INC

Hyperthermia has been used for cancer therapy for along period of time, but has shown limited clinical efficacy. Induction-heating hyperthermia using the combination of magnetic nanoparticles (MNPs) and an alternating magnetic field (AMF), termed magnetic hyperthermia (MHT), has previously shown efficacy in an orthotopic mouse model of disseminated gastric cancer. In the present study, superparamagnetic iron oxide nanoparticles (SPIONs), atype of MNP, were conjugated with an anti-HER2 antibody, trastuzumab and termed anti-HER2-antibody-linked SPION nanoparticles (anti-HER2 SPIONs). Anti-HER2 SPIONs selectively targeted HER2-expressing cancer cells co-cultured along with normal fibroblasts and HER2-negative cancer cells and caused apoptosis only in the HER2-expressing individual cancer cells. The results of the present study show proof-of-concept of anovel hyperthermia technology, immuno-MHT for selective cancer therapy, that targets individual cancer cells.AbbreviationsAMF:alternating magnetic fieldDDW:double distilled waterDMEM:Dulbecco's Modified Eagle's Mediumf:frequencyFBS:fetal bovine serumFITC:Fluorescein isothiocyanateGFP:green fluorescent proteinH:amplitudeHsp:heat shock proteinMHT:magnetic hyperthermiaMNPs:magnetic nanoparticlesPI:propidium iodideRFP:red fluorescent proteinSPION:superparamagnetic iron oxide (Fe3O4) nanoparticle.

DOI： 10.1080/15384101.2021.1915604

Hyperthermia generated by magnetic nanoparticles for effective treatment of disseminated peritoneal cancer in an orthotopic nude-mouse model. International journal

Yuki Matsumi, Tetsuya Kagawa, Shuya Yano, Hiroshi Tazawa, Kunitoshi Shigeyasu, Sho Takeda, Toshiaki Ohara, Hiromichi Aono, Robert M Hoffman, Toshiyoshi Fujiwara, Hiroyuki Kishimoto

Cell cycle (Georgetown, Tex.) 20 ( 12 ) 1 - 12 2021.6

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS INC

Magnetic hyperthermia (MHT), which combines magnetic nanoparticles (MNPs) with an alternating magnetic field (AMF), holds promise as a cancer therapy. There have been many studies about hyperthermia, most of which have been performed by direct injection of MNPs into tumor tissues. However, there have been no reports of treating peritoneal disseminated disease with MHT to date. In the present study, we treated peritoneal metastasis of gastric cancer with MHT using superparamagnetic iron oxide (Fe3O4) nanoparticle (SPION) coated with carboxydextran as an MNP, in an orthotopic mouse model mimicking early peritoneal disseminated disease of gastric cancer. SPIONs of an optimal size were intraperitoneally administered, and an AMF (390 kHz, 28 kAm-1) was applied for 10 minutes, four times every three days. Three weeks after the first MHT treatment, the peritoneal metastases were significantly inhibited compared with the AMF-alone group or the untreated-control group. The results of the present study show that MHT can be applied as a new treatment option for disseminated peritoneal gastric cancer.Abbreviations: AMF: alternating magnetic field; Cy1: cytology-positive; DMEM: Dulbecco's Modified Eagle's Medium; FBS: fetal bovine serum; H&E: hematoxylin and eosin; HIPEC: hyperthermic intraperitoneal chemotherapy; MEM: Minimum Essential Medium; MHT: magnetic hyperthermia; MNPs: magnetic nanoparticles; P0: macroscopic peritoneal dissemination; RFP: red fluorescent protein; SPION: superparamagnetic iron oxide (Fe3O4) nanoparticle.

DOI： 10.1080/15384101.2021.1919441

Clinical and epigenetic features of colorectal cancer patients with somatic POLE proofreading mutations. International journal

Takashi Kawai, Akihiro Nyuya, Yoshiko Mori, Takehiro Tanaka, Hiroaki Tanioka, Kazuya Yasui, Toshiaki Toshima, Fumitaka Taniguchi, Kunitoshi Shigeyasu, Yuzo Umeda, Toshiyoshi Fujiwara, Makoto Okawaki, Yoshiyuki Yamaguchi, Ajay Goel, Takeshi Nagasaka

Clinical epigenetics 13 ( 1 ) 117 - 117 2021.5

Language：English Publishing type：Research paper (scientific journal) Publisher：BMC

BACKGROUND: Mutations in the POLE gene result in an ultra-hypermutated phenotype in colorectal cancer (CRC); however, the molecular characterisation of epigenetic alterations remains unclear. We examined the genetic and epigenetic profiles of POLE-mutant CRC to elucidate the clinicopathological features of the associated genetic and epigenetic alterations. RESULTS: Tumour tissues (1,013) obtained from a cohort of patients with CRC were analysed to determine associations between the proofreading domain mutations of POLE with various clinicopathological variables, microsatellite instability (MSI) status, BRAF and KRAS mutations, and the methylation status of key regions of MLH1, MGMT, and SFRP2 promoters by calculating the methylation scores (range 0-6). Only four cases (0.4%) exhibited pathogenic POLE hotspot mutations (two p.P286R [c.857C > G], one p.V411L [c.1231G > C], and p.S459F [c.1376C > T] each), which were mutually exclusive to BRAF and KRAS mutations and MSI. CRC patients were divided into four subgroups: patients with POLE mutations (POLE, 0.4%, n = 4), patients with both MSI and extensive methylation in MLH1 (MSI-M, 2.9%, n = 29), patients with MSI but no extensive methylation in MLH1 (MSI-U, 3.6%, n = 36), and patients without MSI (non-MSI, 93.2%, n = 944). The POLE group was younger at diagnosis (median 52 years, P < 0.0001), with frequent right-sided tumour localisation (frequency of tumours located in the right colon was 100%, 93.1%, 36.1%, and 29.9% in POLE, MSI-M, MSI-U, and non-MSI, respectively; P < 0.0001), and was diagnosed at an earlier stage (frequency of stages I-II was 100%, 72.4%, 77.8%, and 46.6% in POLE, MSI-M, MSI-U, and non-MSI, respectively, P < 0.0001). The mean methylation score in POLE was not different from that in MSI-U and non-MSI, but the methylation signature was distinct from that of the other subgroups. Additionally, although the examined number of POLE-mutant tumours was small, the number of CD8-positive cells increased in tumours with partial methylation in the MLH1 gene. CONCLUSIONS: CRC patients with POLE proofreading mutations are rare. Such mutations are observed in younger individuals, and tumours are primarily located in the right colon. Diagnosis occurs at an earlier stage, and distinct epigenetic alterations may be associated with CD8 cell infiltration.

DOI： 10.1186/s13148-021-01104-7

SMAD4 Germline Pathogenic Variant-Related Gastric Juvenile Polyposis with Adenocarcinoma Treated with Laparoscopic Total Gastrectomy: A Case Report International journal

Yuya Sakurai, Satoru Kikuchi, Kunitoshi Shigeyasu, Yoshihiko Kakiuchi, Takehiro Tanaka, Hibiki Umeda, Masaki Sakamoto, Sho Takeda, Shuya Yano, Mashu Futagawa, Fumino Kato, Reimi Sogawa, Hideki Yamamoto, Shinji Kuroda, Yoshitaka Kondo, Fuminori Teraishi, Hiroyuki Kishimoto, Masahiko Nishizaki, Shunsuke Kagawa, Akira Hirasawa, Toshiyoshi Fujiwara

American Journal of Case Reports 22 e932241 2021.5

Language：English Publishing type：Research paper (scientific journal) Publisher：International Scientific Information, Inc.

Objective: Rare diseaseBackground: Juvenile polyposis syndrome is an uncommon, autosomal-dominant hereditary disease that is distinguished by multiple polyps in the stomach or intestinal tract. It is associated with a high risk of malignancy. Pathogenic variants in SMAD4 or BMPR1A account for 40% of all cases.Case Report: A 49-year-old woman underwent esophagogastroduodenoscopy because of exacerbation of anemia. She had numerous erythematous polyps in most parts of her stomach. Based on biopsy findings, juvenile polyposis syndrome (JPS) was suspected morphologically, but there was no evidence of malignancy. Colonoscopy showed stemmed hyperplastic polyps and an adenoma; video capsule endoscopy revealed no lesions in the small intestine. After preoperative surveillance, laparoscopic total gastrectomy with D1 lymph node dissection was performed to prevent malignant transformation. The pathological diagnosis was juvenile polyp-like polyposis with adenocarcinoma. In addition, a germline pathogenic variant in the SMAD4 gene was detected with genetic testing.Conclusions: JPS can be diagnosed with endoscopy and genetic testing. Further, appropriate surgical management may prevent cancer-related death in patients with this condition.

DOI： 10.12659/ajcr.932241

Long-term Survival with a Rare Advanced Primary Gastrointestinal Malignant Melanoma Treated with Laparoscopic Surgery/Immune Checkpoint Inhibitor.

Motochika Endo, Shuya Yano, Hiroaki Asano, Sho Takeda, Yuki Hamada, Yoshitaka Kondo, Shinji Kuroda, Kunitoshi Shigeyasu, Satoru Kikuchi, Takehiro Tanaka, Fuminori Teraishi, Masahiko Nishizaki, Shunsuke Kagawa, Toshiyoshi Fujiwara

Acta medica Okayama 75 ( 2 ) 231 - 238 2021.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

Targeted therapies for malignant melanoma have improved patients' prognoses. A primary gastrointestinal malignant melanoma is very rare, with no standard treatment strategy. We treated a 78-year-old Japanese female with advanced primary gastrointestinal melanoma of the descending colon and gallbladder. We administered a multidisciplinary treatment: surgical resection of the descending colon and gallbladder tumors, resection of the metastatic lymph nodes behind the pancreas head, and immune checkpoint antibody-blockade therapy (nivolumab) for ~4 years. PET/CT demonstrated no recurrent lesion for > 3 years. Multidisciplinary therapies (e.g., surgery, chemotherapy, radiotherapy, target therapy, and immune checkpoint antibody-blockade therapy) can successfully treat primary gastrointestinal malignant melanoma.

DOI： 10.18926/AMO/61906

Perspective and prospective of RNA editing in colorectal cancer microenvironment

Sho Takeda, Kunitoshi Shigeyasu, Yasuhiro Komatsu, Kazutaka Takahashi, Nanako Hata, Kazuhiro Yoshida, Shuya Yano, Yoshitaka Kondo, Fuminori Teraishi, Yuzo Umeda, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara

CANCER SCIENCE 112 481 - 481 2021.2

Reversible EMT-MET biosensor-mediated imaging visualizes inducible resistance to chemotherapy with hybrid E/M phase

Naoki Mimura, Shuya Yano, Hiroshi Tazawa, Takeshi Ieda, Daiki Okabayashi, Kunitoshi Shigeyasu, Sho Takeda, Kazuhiro Yoshida, Fuminori Teraishi, Yuzo Umeda, Shunsuke Kagawa, Toshiyoshi Fujiwara

CANCER SCIENCE 112 193 - 193 2021.2

RNA editing activated by chemoradiation therapy artificially generates neoantigen in colorectal cancer

Yasuhiro Komatsu, Kunitoshi Shigeyasu, Sho Takeda, Kazutaka Takahashi, Nanako Hata, Kazuhiro Yoshida, Shuya Yano, Toshiaki Ohara, Kazuhiro Noma, Yuzo Umeda, Shinji Kuroda, Yoshitaka Kondo, Fuminori Teraishi, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara

CANCER SCIENCE 112 336 - 336 2021.2

　 PREV - NEXT 　

1
2
3
4
5