Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Despite continuing advances in the development of effective new therapies, including immunotherapies, the prognosis of pancreatic cancer remains extremely poor. Gap junction proteins have become attractive targets for potential cancer therapy. However, the role of gap junction beta‐4 (GJB4) protein remains unexplored in pancreatic cancer. Through bioinformatic analyses we discovered pancreatic cancer tissues showed higher levels of GJB4 transcripts compared to normal pancreatic tissues and this had a negative effect on overall survival in patients that had pancreatic cancer. The high expression of nuclear GJB4 was identified as a negative prognostic factor in such patients. Knockdown of GJB4 in cultured pancreatic cancer cells resulted in G₀/G₁ arrest followed by decreased cell proliferation and suppression of metastatic potential. The overexpression of GJB4 accelerated cell proliferation, migration, and invasion in a SUIT‐2 cell line, whereas MET inhibitor canceled the acceleration. GJB4 suppression with siRNA significantly inhibited tumor growth in a mouse xenograft model. Mechanistically, suppression of GJB4 inhibited MET–AKT activities. Such data suggest that targeting the GJB4–MET axis could represent a promising new therapeutic strategy for pancreatic cancer.

DOI： 10.1111/cas.16101

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

A 50-year-old man with a history of total gastrectomy, distal pancreatectomy, splenectomy, and Roux-en-Y reconstruction was admitted to our hospital with a gallbladder tumor that had infiltrated the liver and abdominal wall. Because malignant cells were not collected during the percutaneous biopsy, we planned to perform an endoscopic ultrasound-guided fine-needle biopsy with a 22-G Franseen needle using a forward-viewing echoendoscope. Using intermittent manual compression, the forward-viewing echoendoscope reached the duodenum under fluoroscopic guidance. Endoscopic ultrasound-guided fine-needle biopsy was performed using a 22-G needle and 20-mL syringe and yielded a sufficient specimen with a single puncture. Malignant cells were promptly identified during on-site evaluation. The composition of the specimen (> 20% cancer cells and tissue area exceeding 25 mm2) enabled comprehensive genomic profiling. Subsequently, high-tumor mutational burden was diagnosed based on comprehensive genomic profiling, and pembrolizumab was initiated as a second-line therapy. Even in cases involving Roux-en-Y reconstruction, endoscopic ultrasound-guided fine-needle biopsy using a forward-viewing echoendoscope can result in collection of a high-quality specimen.

DOI： 10.1007/s12328-023-01876-w

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

PURPOSE: To determine, for patients with advanced or recurrent synovial sarcoma not suitable for surgical resection and resistant to anthracycline, the safety and efficacy of the infusion of autologous T lymphocytes expressing NY-ESO-1 antigen-specific T-cell receptor gene and siRNAs to inhibit the expression of endogenous T-cell receptors (product code: TBI-1301). PATIENTS AND METHODS: Eligible Japanese patients (HLA-A*02:01 or *02:06, NY-ESO-1-positive tumor expression) received cyclophosphamide 750 mg/m2 on days -3 and -2 (induction period) followed by a single dose of 5 x 109 (±30%) TBI-1301 cells as a divided infusion on days 0 and 1 (treatment period). Primary endpoints were safety-related (phase I part) and efficacy-related (objective response rate [ORR] by RECIST v1.1/irRECIST; phase II part). Safety- and efficacy-related secondary endpoints were considered in both phase I/II parts. RESULTS: For the full analysis set (N=8; phase I, n=3; phase II, n=5), the ORR was 50.0% (95%CI: 15.7-84.3) with best overall partial response in 4 of 8 patients according to RECIST v1.1/irRECIST. All patients experienced adverse events and 7 of 8 patients (87.5%) had adverse drug reactions but no deaths were attributed to adverse events. Cytokine release syndrome occurred in 4 of 8 patients (50.0%) but all cases recovered with prespecified treatment. Immune effector cell-associated neurotoxicity syndrome, replication competent retrovirus, and lymphocyte clonality were absent. CONCLUSIONS: Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1 positive tumor cells appears to be a promising strategy for the treatment of advanced or recurrent synovial sarcoma with acceptable toxicity.

DOI： 10.1158/1078-0432.CCR-23-1456

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Accumulating evidence has demonstrated platinum-based chemotherapy followed by maintenance therapy with a poly Adenosine diphosphate (ADP)-ribose polymerase inhibitor (olaparib) show benefits in unresectable pancreatic cancer with a germline (g)BRCA1/2 mutation. Evaluation of the germline BRCA1 and BRCA2 mutation is essential for making decisions on a treatment strategy for patients with unresectable pancreatic cancer. However, the detection rates of germline BRCA1 and BRCA2 mutations and efficacy of maintenance with olaparib remain undetermined, prospectively, in Japan. METHODS & RESULTS: In this prospective analysis, the rate of germline BRCA1 and BRCA2 mutations and efficacy of chemotherapy were analyzed in 136 patients with pancreatic cancer who underwent BRACAnalysis® (85 patients) or FoundationOne® CDx (51 patients) between January 2020 and July 2022. A total of six patients (4.4%) had a germline BRCA1 and BRCA2 mutation. Five patients were treated with modified FOLFIRINOX and one with fluorouracil and oxaliplatin. All patients continued platinum-based chemotherapy for ˃4 months and were subsequently treated with olaparib as a maintenance therapy. The response rate to platinum-based chemotherapy in the germline BRCA1 and BRCA2 mutation-positive group was significantly better than that of the germline BRCA1 and BRCA2 mutation-negative group (66% vs 23%, P = 0.04). All patients harbouring a germline BRCA1 and BRCA2 mutation were able to switch to olaparib. The median progression-free survival using olaparib was 5.7 months (range 3.0-9.2). CONCLUSIONS: The rate of germline BRCA1 and BRCA2 mutations found in patients with unresectable pancreatic cancer was comparable to those of previous studies.An analysis of germline BRCA1 and BRCA2 mutations has benefits for all patients with unresectable pancreatic cancer with regard to decisions on therapeutic strategies in a clinical practice setting.

DOI： 10.1093/jjco/hyad131

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Other Link： https://link.springer.com/article/10.1007/s00256-023-04457-7/fulltext.html

DOI： 10.1007/s00256-023-04457-7

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Authorship：Last author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Ipilimumab plus nivolumab therapy is approved for patients with unresectable advanced esophageal squamous cell carcinoma (ESCC). Although a combination of immune checkpoint inhibitors (ICIs), compared to conventional chemotherapy, can improve overall survival in patients with advanced ESCC, this increases the incidence of immune-related adverse events (irAEs). Here, we describe an ESCC case that developed pemphigus vulgaris (PV), an extremely rare cutaneous irAE, during ipilimumab plus nivolumab treatment. The patient achieved a partial response to treatment. The PV was successfully managed after the cessation of ipilimumab and the use of a topical steroid. We should thus re-treat ESCC with nivolumab monotherapy. In the era of ICIs as standard cancer therapeutics, diagnostic criteria for blistering diseases need to be established to properly manage patients with cutaneous irAEs.

DOI： 10.3389/fimmu.2023.1259071

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

The current study's objective was to elucidate some currently unknown biological indicators to evaluate the biological nature of cancer-associated fibroblasts (CAFs). For this purpose, four different CAFs, CAFS1, CAFS2, SCC17F and MO-1000, were established using surgical specimens from oral squamous cell carcinomas (OSCC) with different clinical malignant stages (CAFS1 and CAFS2, T2N0M0, stage II; SCC17F and MO-1000, T4aN2bM0, stage IVA). Fibroblasts unrelated to cancer (non-CAFs) were also prepared and used as controls. Initially, confirmation that these four fibroblasts were indeed CAFs was obtained by their mRNA expression using positive and negative markers for the CAF or fibroblasts. To elucidate possible unknown biological indicators, these fibroblasts were subjected to a cellular metabolic analysis by a Seahorse bioanalyzer, in conjugation with 3D spheroid cultures of the cells and co-cultures with a pancreas ductal carcinoma cell line, MIA PaCa-2. The mitochondrial and glycolytic functions of human orbital fibroblasts (HOF) were nearly identical to those of Graves'-disease-related HOF (GOF). In contrast, the characteristics of the metabolic functions of these four CAFs were different from those of human conjunctival fibroblasts (HconF), a representative non-CAF. It is particularly noteworthy that CAFS1 and CAFS2 showed markedly reduced ratios for the rate of oxygen consumption to the extracellular acidification rate, suggesting that glycolysis was enhanced compared to mitochondrial respiration. Similarly, the physical aspects, their appearance and stiffness, of their 3D spheroids and fibroblasts that were induced effects based on the cellular metabolic functions of MIA PaCa-2 were also different between CAFs and non-CAFs, and their levels for CAFS1 or SCC17F were similar to those for CAFS2 or MO-1000 cells, respectively. The findings reported herein indicate that cellular metabolic functions and the physical characteristics of these types of 3D spheroids may be valuable and useful indicators for estimating potential biological diversity among various CAFs.

DOI： 10.3390/cells12172160

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Other Link： https://link.springer.com/article/10.1007/s13577-023-00944-0/fulltext.html

DOI： 10.1007/s13577-023-00944-0

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

The efficacy of immune checkpoint inhibitors is limited in refractory solid tumors. T-cell receptor gene-modified T (TCR-T)-cell therapy has attracted attention as a new immunotherapy for refractory cold tumors. We first investigated the preclinical efficacy and mode of action of TCR-T cells combined with the pullulan nanogel:long peptide antigen (LPA) vaccine in a mouse sarcoma model that is resistant to immune checkpoint inhibition. Without lymphodepletion, the pullulan nanogel:LPA vaccine markedly increased the number of TCR-T cells in the draining lymph node and tumor tissue. This change was associated with enhanced CXCR3 expression in TCR-T cells in the draining lymph node. In the phase 1 trial, autologous New York esophageal squamous cell carcinoma 1 (NY-ESO-1)-specific TCR-T cells were infused twice into HLA-matched patients with NY-ESO-1+ soft tissue sarcoma (STS). The pullulan nanogel:LPA vaccine contains an epitope recognized by TCR-T cells, and it was subcutaneously injected 1 day before and 7 days after the infusion of TCR-T cells. Lymphodepletion was not performed. Three patients with refractory synovial sarcoma (SS) were treated. Two out of the three patients developed cytokine release syndrome (CRS) with low-to-moderate cytokine level elevation. We found obvious tumor shrinkage lasting for more than 2 years by tumor imaging and long-term persistence of TCR-T cells in one patient. In conclusion, NY-ESO-1-specific TCR-T-cell therapy plus vaccination with the pullulan nanogel carrying an LPA containing the NY-ESO-1 epitope without lymphodepletion is feasible and can induce promising long-lasting therapeutic effects in refractory SS (Registration ID: JMA-IIA00346).

DOI： 10.1002/ijc.34453

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

Comprehensive genomic profiling (CGP) tests have been covered by public insurance in Japan for patients with advanced solid tumors who have completed or are completing standard treatments or do not have them. Therefore, genotype-matched drug candidates are often unapproved or off-label, and improving clinical trial access is critical, involving the appropriate timing of CGP tests. To address this issue, we analyzed the previous treatment data for 441 patients from an observational study on CGP tests discussed by the expert panel at Hokkaido University Hospital between August 2019 and May 2021. The median number of previous treatment lines was two; three or more lines accounted for 49%. Information on genotype-matched therapies was provided to 277 (63%). Genotype-matched clinical trials were ineligible because of an excess number of previous treatment lines or use of specific agents were found in 66 (15%) patients, with the highest proportion in breast and prostate cancers. Many patients met the exclusion criteria of one to two or more treatment lines across cancer types. In addition, previous use of specific agents was a frequent exclusion criterion for breast, prostate, colorectal, and ovarian cancers. The patients with tumor types with a low median number (two or fewer) of previous treatment lines, including most rare cancers, primary unknown cancers, and pancreatic cancers, had significantly fewer ineligible clinical trials. The earlier timing of CGP tests may improve access to genotype-matched clinical trials, with their proportion varying by cancer type. Each relevant society needs to advocate the desirable timing of CGP testing nationwide.

DOI： 10.1111/cas.15837

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Language：English  

DOI： 10.1111/ped.15653

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

INTRODUCTION: Adoptive cell transfer of genetically engineered T cells is a promising treatment for malignancies; however, there are few ideal cancer antigens expressed on the cell surface, and the development of chimeric antigen receptor T cells (CAR-T cells) for solid tumour treatment has been slow. CAR-T cells, which recognise major histocompatibility complex and peptide complexes presented on the cell surface, can be used to target not only cell surface antigens but also intracellular antigens. We have developed a CAR-T-cell product that recognises the complex of HLA-A*02:01 and an epitope of the MAGE-A4 antigen equipped with a novel signalling domain of human GITR (investigational product code: MU-MA402C) based on preclinical studies. METHODS AND ANALYSIS: This is a dose-escalation, multi-institutional, phase 1 study to evaluate the tolerability and safety of MU-MA402C for patients with MAGE A4-positive and HLA-A*02:01-positive unresectable advanced or recurrent solid cancer. Two dose cohorts are planned: cohort 1, MU-MA402C 2×108/person; cohort 2, MU-MA402C 2×109/person. Prior to CAR-T-cell infusion, cyclophosphamide (CPA) and fludarabine (FLU) will be administered as preconditioning chemotherapy. Three evaluable subjects per cohort, for a total of 6 subjects (maximum of 12 subjects), will be recruited for this clinical trial. The primary endpoints are safety and tolerability. The severity of each adverse event will be evaluated in accordance with Common Terminology Criteria for Adverse Events V.5.0. The secondary endpoint is efficacy. Antitumour response will be evaluated according to Response Evaluation Criteria in Solid Tumours V.1.1. ETHICS AND DISSEMINATION: This clinical trial will be conducted in accordance with the current version of Good Clinical Practice. The protocol was approved by the Clinical Research Ethics Review Committee of Mie University Hospital (approval number F-2021-017). The trial results will be published in peer-reviewed journals and/or disseminated through international conferences. TRIAL REGISTRATION NUMBER: jRCT2043210077.

DOI： 10.1136/bmjopen-2022-065109

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Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：AME Publishing Company  

DOI： 10.21037/apm-22-536

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Characterization of the genomic landscape of biliary tract cancer (BTC) may lead to applying genotype-matched therapy for patients with this disease. Evidence that comprehensive cancer genomic profiling (CGP) guides genotype-matched therapy to improve clinical outcomes is building. However, the significance of CGP in patients with BTC remains unclarified in clinical practice. Therefore, the purposes of this study were to assess the utility of CGP and identify associations between clinical outcomes and genomic alterations in patients with BTC. In this prospective analysis, detection rates for actionable genomic alterations and access rates for genotype-matched therapy were analyzed in 72 patients with advanced BTC who had undergone commercial CGP. Cox regression analyses assessed relationships between overall survival and genomic alterations detected with CGP. The most common genomic alterations detected were TP53 (41, 56.9%), followed by CDKN2A/B (24, 33.3%/20, 27.8%), and KRAS (20, 27.8%). Actionable genomic alterations were identified in 58.3% (42/72) of patients. Detection rates for FGFR2 fusions, IDH1 mutations, and BRAF V600E were low in this cohort. Eight (11.1%) patients received genotype-matched therapy. For patients with intrahepatic cholangiocarcinoma (ICC), CDKN2A/B loss was associated with shorter overall survival. These real-world data demonstrate that CGP can identify therapeutic options in patients with advanced BTC. CDKN2A/B loss was identified as a poor prognostic factor in patients with ICC. Thus, this study provides a rationale for considering CGP in planning therapeutic strategies for advanced BTC.

DOI： 10.3389/fonc.2022.988527

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BACKGROUND: Predicting the prognosis of patients with solitary fibrous tumor (SFT) is often difficult. The prognostic risk models developed by Demicco et al. are now the standard for evaluating the risk of SFT metastasis in the current World Health Organization classification of soft tissue and bone tumors. METHODS: In this study, we examined the prognostic usefulness of a modified version of the Demicco risk models that replaces the mitotic count with the Ki-67 labeling index. We compared the three-variable and four-variable Demicco risk models with our modified risk models using Kaplan-Meier curves based on data for 43 patients with SFT. RESULTS: We found a significant difference in metastasis-free survival when patients were classified into low-risk and intermediate/high-risk groups using the three-variable (P = 0.022) and four-variable (P = 0.046) Demicco models. There was also a significant difference in metastasis-free survival between the low-risk and intermediate/high-risk groups when the modified three-variable (P = 0.006) and four-variable (P = 0.022) models were used. CONCLUSION: Modified risk models that include the Ki-67 labeling index are effective for prediction of the prognosis in patients with SFT.

DOI： 10.1186/s12957-022-02497-2

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.9423-22

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

An 18-year-old man presented with sudden vision loss in his left eye. Magnetic resonance imaging revealed a tumor that had invaded the left optic nerve, originating from the left posterior ethmoid sinus. Immunohistochemical analyses identified positive staining for NUT protein in the nuclei of tumor cells. We diagnosed locally advanced NUT carcinoma (NC) and initiated concurrent chemoradiotherapy (CCRT), consisting of chemotherapy with vincristine, doxorubicin, and cyclophosphamide, alternating with ifosphamide and etoposide, plus radiation therapy. The patient achieved a complete response. CCRT can be a useful treatment option for adolescent and young-adult patients with locally advanced unresectable NC.

DOI： 10.2169/internalmedicine.7741-21

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Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.15068

DOI： 10.1111/cas.15068

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

PURPOSE: The clinical benefit of conversion surgery (CS) for unresectable gastric cancer (GC), whereby unresectable GC responds to chemotherapy and subsequently receives curative-intent surgery, remains unclear. Here, we aimed to clarify the clinical value of CS. METHODS: In this retrospective cohort study, we analyzed 175 unresectable GC, who received triple combined chemotherapy between 2004 and 2019. We divided patients into two groups: those who underwent CS and those receiving chemotherapy only (CS and C groups, respectively). Propensity score matching was used to minimize confounding bias. RESULTS: Of 175 cases, 61 (34.9%) underwent CS. R0 resection was obtained in 85.2%. After matching, 44 pairs were selected; there were no significant differences in baseline covariants. Group CS had a significantly better median overall survival (OS) (18.8 vs. 46.0 months, p < 0.001), and prolonged progression-free survival (7.4 vs. 25.8 months, p < 0.001). Subgroup analysis of OS showed a favorable trend for CS for almost all subgroups. Multivariate analysis revealed that good ECOG performance status and CS were associated with a longer OS. CONCLUSION: The survival benefit of CS was consistently demonstrated in the univariate and multivariate analysis, even in the matched cohort. Additional large-scale trials are needed for further validation.

Other Link： https://link.springer.com/article/10.1007/s00432-021-03516-7/fulltext.html

DOI： 10.1007/s00432-021-03516-7

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Spandidos Publications  

Six-transmembrane epithelial antigen of the prostate 1 (STEAP1) has emerged as an ideal target in cancer therapeutics. However, the functions of STEAP1 in liver cancer remain unexplored. The current study aimed to characterize the biological roles of STEAP1 in liver cancer. STEAP1 expression was upregulated in tumor tissues, and high STEAP1 expression was associated with poor clinical outcomes in patients with liver cancer, according to several publicly available datasets. STEAP1 silencing using small interfering RNA inhibited cell proliferation and was accompanied by G1 arrest induced by the suppression of cyclin D1 and the promotion of p27. STEAP1 silencing suppressed c-Myc expression, which was identified as a component in STEAP1 signal transduction by mining publicly available datasets and was then confirmed by PCR array. In conclusion, the knockdown of STEAP1 in liver cancer cell lines led to inhibition of cell proliferation involving G1 arrest by suppressing c-Myc. The present study provides a preclinical concept for STEAP1 as a druggable target in liver cancer.

DOI： 10.3892/ol.2021.12807

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

<title>Abstract</title>
<sec>
<title>Background</title>
Comprehensive cancer genomic profiling has been used recently for patients with advanced solid cancers. Two cancer genomic profiling tests for patients with no standard treatment are covered by Japanese public health insurance since June 2019.


</sec>
<sec>
<title>Methods</title>
We prospectively analyzed data of 189 patients with solid cancers who underwent either of the two-cancer genomic profiling tests at Hokkaido University Hospital and its liaison hospitals and whose results were discussed in molecular tumor board at Hokkaido University Hospital between August 2019 and July 2020.


</sec>
<sec>
<title>Results</title>
All 189 patients had appropriate results. Actionable gene alterations were identified in 93 patients (49%). Frequent mutations included PIK3CA (12%) mutation, BRCA1/2 alteration (7%), ERBB2 amplification (6%) and tumor mutation burden-High (4%). The median turnaround time from sample shipping to acquisition by the expert panel was 26 days. Although 115 patients (61%) were provided with information for genotype-matched therapies, only 21 (11%) received them. Notably, four of eight patients below the age of 20 years were provided information for genotype-matched therapies, and three received them. Their response rates and disease control rates were 29% and 67%, respectively. Most patients who did not undergo the genotype-matched therapies were provided information for only investigational drugs in phases I and II at distant clinical trial sites in central Japan. Twenty-six patients were informed of suspected germline findings, while 11 patients (42%) received genetic counseling.


</sec>
<sec>
<title>Conclusions</title>
The publicly reimbursed cancer genomic profilings may lead to the modest but favorable therapeutic efficacy of genotype-matched therapy for solid cancer patients with no standard therapy. However, poor access to genotype-matched therapy needs to be resolved.


</sec>

DOI： 10.1093/jjco/hyaa277

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Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.3597

DOI： 10.1002/ccr3.3597

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1759-7714.13751

DOI： 10.1111/1759-7714.13751

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Baishideng Publishing Group Inc.  

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome often associated with germline mutations in the CDH1 gene. However, the frequency of CDH1 mutations is low in patients with HDGC in East Asian countries. Herein, we report three cases of HDGC harboring a missense CDH1 variant, c.1679C>G, from a single Japanese family. CASE SUMMARY: A 26-year-old female (Case 1) and a 51-year-old male (father of Case 1), who had a strong family history of gastric cancer, were diagnosed with advanced diffuse gastric cancer. After genetic counselling, a 25-year-old younger brother of Case 1 underwent surveillance esophagogastroduodenoscopy that detected small signet ring cell carcinoma foci as multiple pale lesions in the gastric mucosa. Genetic analysis revealed a CDH1 c.1679C>G variant in all three patients. CONCLUSION: It is important for individuals suspected of having HDGC to be actively offered genetics evaluation. This report will contribute to an increased awareness of HDGC.

DOI： 10.3748/wjg.v26.i42.6689

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Hindawi Limited  

Papillary thyroid cancer (PTC) is considered an indolent cancer, but some PTC patients do present with distant metastases and treatment strategies for such patients are not well established. Recently, lenvatinib, an inhibitor of multiple tyrosine kinases, has been introduced to treat patients with advanced PTC but carries a risk of serious adverse events such as hemorrhage. Here, we report a PTC patient with a left adrenal metastasis and lenvatinib-induced hemorrhage who underwent successful surgical resection and was subsequently treated with a lower dose of lenvatinib. The patient has now been in a stable state with no adverse events for nearly two years. This case highlights the importance of surgical resection of metastatic PTC and subsequent lenvatinib therapy, even when the tumor is at an advanced stage.

Other Link： http://downloads.hindawi.com/journals/crionm/2020/2107430.xml

DOI： 10.1155/2020/2107430

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Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1097/mpa.0000000000001462

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

<italic>Background</italic>. Lymph node metastasis (LNM) is a relatively rare event in soft tissue sarcoma. An association between the timing of LNM detection and patient prognosis is presently unknown. <italic>Patients and Methods</italic>. We retrospectively analyzed the clinicopathological features of 33 patients with LNM between 2001 and 2015. Analysis of the timing of LNM diagnosis was grouped according to patients presenting LNM in either &lt;8 months (the median time from primary tumor diagnosis to LNM) or ≥8 months after primary tumor diagnosis. <italic>Results</italic>. A relationship between the primary tumor size and the timing of the LNM was not significantly found (<italic>Rs</italic> = 0.0088, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.96</mml:mn></mml:mrow></mml:math>). Sixteen patients had an LNM detection duration of &lt;8 months, and 17 patients had a duration of ≥8 months. The 5-year survival for patients with an LNM detection duration of &lt;8 months and ≥8 months was 19% and 71%, respectively (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.0016</mml:mn></mml:mrow></mml:math>). There were 19 patients with pulmonary metastases. Among them, there were 13 patients with a duration of primary tumor diagnosis to LNM of &lt;8 months and 6 with a duration of ≥8 months (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.01</mml:mn></mml:mrow></mml:math>). <italic>Conclusion</italic>. Early LNM (&lt;8 months) may predict poor prognosis in soft tissue sarcoma.

Other Link： http://downloads.hindawi.com/journals/ijso/2019/6708474.xml

DOI： 10.1155/2019/6708474

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DOI： 10.1016/j.oraloncology.2019.104509

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

BACKGROUND: Primary soft tissue sarcomas (STSs) involving the chest wall are uncommon. The aim of this study was to identify factors that influence the prognosis of patients with primary chest wall STS. METHODS: The records of 38 patients (23 men and 15 women) who were treated at our institutions during 2002 to 2018 were reviewed. The following variables were evaluated as potential prognostic factors: sex, tumor size, chemotherapy, and completeness of surgical margins. Multivariate analysis was conducted to identify predictors of overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 38 included patients, 5 had low-grade tumors and 33 had high-grade tumors. Five patients required chest wall reconstruction including rib resection. Thirty patients (79%) underwent R0 resection. The 5-year OS and DFS rates were 45% and 27%, respectively. Local recurrence developed in 7 patients. Multivariate analysis identified tumor size (hazard ratio [HR]: 4.13; 95% confidence interval [CI]: 1.05-16.24; P = .04) and R1/2 resection (HR: 3.92; 95% CI: 1.12-13.66; P = .03) as predictors of OS. CONCLUSIONS: Prognostic factors for survival included tumor size and completeness of surgical margins. Complete tumor excision is desirable, particularly in cases of early detection.

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jso.25708

DOI： 10.1002/jso.25708

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a new clinical entity characterized by SMARCA4 inactivation and has a dismal prognosis because of rapid growth. Effective treatments for SMARCA4-DTS have not yet been developed. Most recently, anti-programmed cell death 1 receptor (PD-1) blockade has been effective for SMARCA4-deficient lung cancer and malignant rhabdoid tumor-like tumors. Here, we describe a patient with SMARCA4-DTC who experienced a marked response to the administration of pembrolizumab. A 70-year-old female was referred to our department for treatment of SMARCA4-DTC. Positron emission tomography-computed tomography had revealed a left mediastinal tumor, peritoneal dissemination and multiple cutaneous metastases at diagnosis. Immunohistochemical analyses revealed 60% of tumor cells expressed programmed cell death ligand 1 (PD-L1). The patient was given pembrolizumab as first-line treatment. Pembrolizumab suppressed tumor growth dramatically, with only one dose leading to a partial response. Our case suggests the immunohistochemical analysis of PD-L1 expression be undertaken for patients with SMARCA4-DTS and that pembrolizumab treatment may be a promising strategy for PD-L1-positive SMARCA4-DTS.

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1759-7714.13215

DOI： 10.1111/1759-7714.13215

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title>Dipeptidyl peptidases (DPPs) are proteolytic enzymes that are ideal therapeutic targets in human diseases. Indeed, DPP4 inhibitors are widely used in clinical practice as anti-diabetic agents. In this paper, we show that DPP4 inhibitors also induced cell death in multiple human myeloma cells. Among five DPP4 inhibitors, only two of them, vildagliptin and saxagliptin, exhibited apparent cytotoxic effects on myeloma cell lines, without any difference in suppression of DPP4 activity. As these two DPP4 inhibitors are known to have off-target effects against DPP8/9, we employed the specific DPP8/9 inhibitor 1G244. 1G244 demonstrated anti-myeloma effects on several cell lines and CD138+ cells from patients as well as in murine xenograft model. Through siRNA silencing approach, we further confirmed that DPP8 but not DPP9 is a key molecule in inducing cell death induced by DPP8/9 inhibition. In fact, the expression of DPP8 in CD38+ cells from myeloma patients was higher than that of healthy volunteers. DPP8/9 inhibition induced apoptosis, as evidenced by activated form of PARP, caspases-3 and was suppressed by the pan-caspase inhibitor Z-VAD-FMK. Taken together, these results indicate that DPP8 is a novel therapeutic target for myeloma treatment.

Other Link： http://www.nature.com/articles/s41598-019-54695-w

DOI： 10.1038/s41598-019-54695-w

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

Pneumothorax has been reported as a pazopanib-associated adverse event in patients with lung metastases of soft tissue sarcoma (STS). However, pneumothorax triggered by eribulin treatment has never been reported. We herein report two cases of spontaneous pneumothorax in patients with STS treated with eribulin. Both patients experienced pneumothorax accompanied by sudden dyspnea on day 9 or 10 of eribulin treatment. These two cases suggest that spontaneous pneumothorax may occur as an adverse event of eribulin treatment in such patients. We should therefore be alert for the potential development of pneumothorax during eribulin treatment of patients with STS and lung metastases.

DOI： 10.2169/internalmedicine.2790-19

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Other Link： http://www.nature.com/articles/s41417-018-0056-8

DOI： 10.1038/s41417-018-0056-8

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

An activated AKT pathway underlies the pathogenesis of soft tissue sarcoma (STS), with over-expressed phosphorylated AKT (p-AKT) correlating with a poor prognosis in a subset of STS cases. Recently, eribulin, a microtubule dynamics inhibitor, has demonstrated efficacy and is approved in patients with advanced/metastatic liposarcoma and breast cancer. However, mechanisms of eribulin resistance and/or insensitivity remain largely unknown. In this study, we demonstrated that an increased p-AKT level was associated with eribulin resistance in STS cells. We found a combination of eribulin with the AKT inhibitor, MK-2206, synergistically inhibited STS cell growth in vivo as well as in vitro. Mechanistically, eribulin plus MK-2206 induced G1 or G2/M arrest by down-regulating cyclin-dependent kinases, cyclins and cdc2, followed by caspase-dependent apoptosis in STS cells. Our findings demonstrate the significance of p-AKT signaling for eribulin-resistance in STS cells and provide a rationale for the development of an AKT inhibitor in combination with eribulin to treat patients with STS.

DOI： 10.1038/s41598-019-42300-z

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.18632/oncotarget.19508

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

Other Link： http://link.springer.com/content/pdf/10.1007/s12185-017-2233-1.pdf

DOI： 10.1007/s12185-017-2233-1

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0168355

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Authorship：Lead author   Language：English  

Deregulated iron metabolism underlies the pathogenesis of many human cancers. Recently, low expression of ferroportin, which is the only identified non-heme iron exporter, has been associated with significantly reduced overall survival in multiple myeloma (MM); however, the altered iron metabolism in MM biology remains unclear. In this study we demonstrated, by live cell imaging, that MM cells have increased intracellular iron levels as compared with normal cells. In experiments to test the effect of iron chelation on the growth of MM cells, we found that deferasirox (DFX), an oral iron chelator used to treat iron overload in clinical practice, inhibits MM cell growth both in vivo and in vitro. Mechanistically, DFX was found to induce apoptosis of MM cells via the inhibition of proline-rich tyrosine kinase 2 (Pyk2), which is known to promote tumor growth in MM. Inhibition of Pyk2 is caused by the suppression of reactive oxygen species, and leads to downregulation of the Wnt/β-catenin signaling pathway. Taken together, our findings indicate that high levels of intracellular iron, which might be due to low ferroportin expression, play a role in MM pathophysiology. Therefore, DFX may provide a therapeutic option for MM that is driven by deregulated iron homeostasis and/or Pyk2/Wnt signaling.

DOI： 10.18632/oncotarget.11830

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Other Link： http://link.springer.com/article/10.1007/s12185-014-1677-9/fulltext.html

DOI： 10.1007/s12185-014-1677-9

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

DOI： 10.1158/0008-5472.CAN-13-3311-T

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

DOI： 10.2169/internalmedicine.53.1970

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

DOI： 10.1111/bjh.12365

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1126/scitranslmed.3003808

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Other Link： http://www.nature.com/articles/leu2011303

DOI： 10.1038/leu.2011.303

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

DOI： 10.1158/0008-5472.CAN-09-0773

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

DOI： 10.1182/blood-2008-12-194290

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Publisher：4  

DOI： 10.1038/nbt1396

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Language：English  

Various complications and potential risks of serious adverse events lessens the intensity of chemotherapy in patients with Werner syndrome. Bone marrow carcinomatosis of breast cancer was developed in a patient with Werner syndrome. Eribulin proved well tolerated and effective in improving severe thrombocytopenia, leading to platelet transfusion-free status.

DOI： 10.1111/ggi.15070

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Other Link： https://link.springer.com/article/10.1007/s13577-024-01157-9/fulltext.html

DOI： 10.1007/s13577-024-01157-9

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

ABSTRACT

Background

Radiotherapy is considered an alternative treatment for unresectable or pharmacologically resistant desmoid‐type fibromatosis. While it results in relatively good local control, the risk of secondary malignancy remains a concern.

Case

We present a case of secondary osteosarcoma after carbon‐ion radiation therapy (CIRT). A 31‐year‐old male patient presented with left thigh pain. The tumor was located between the left gluteus maximus and gluteus medius and extended to the vastus lateralis and biceps femoris. It was diagnosed as desmoid‐type fibromatosis after needle biopsy. The patient was treated with several medications, including a cyclooxygenase 2 inhibitor and tamoxifen; however, his left thigh pain did not improve. He was treated with CIRT 1 year after diagnosis (67.2 Gy [relative biological effectiveness] 16fr/4wks). He developed osteosarcoma of the left femur 8 years later. He underwent chemotherapy and tumor excision with disarticulation of the left hip. Pulmonary metastasis was detected 6 and 17 months after the definitive surgery and excised using metastasectomy. However, he died due to the recurrence of multiple pulmonary metastases 29 months after the definitive surgery.

Conclusions

In this case, we believe that the low radiation dose to the femur may have caused secondary malignancy.

DOI： 10.1002/cnr2.70062

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

Cell culture methods are indispensable strategies for studies in biological sciences and for drug discovery and testing. Most cell cultures have been developed using two-dimensional (2D) culture methods, but three-dimensional (3D) culture techniques enable the establishment of in vitro models that replicate various pathogenic conditions and they provide valuable insights into the pathophysiology of various diseases as well as more precise results in tests for drug efficacy. However, one difficulty in the use of 3D cultures is selection of the appropriate 3D cell culture technique for the study purpose among the various techniques ranging from the simplest single cell type-derived spheroid culture to the more sophisticated organoid cultures. In the simplest single cell type-derived spheroid cultures, there are also various scaffold-assisted methods such as hydrogel-assisted cultures, biofilm-assisted cultures, particle-assisted cultures, and magnet particle-assisted cultures, as well as non-assisted methods, such as static suspension cultures, floating cultures, and hanging drop cultures. Since each method can be differently influenced by various factors such as gravity force, buoyant force, centrifugal force, and magnetic force, in addition to non-physiological scaffolds, each method has its own advantages and disadvantages, and the methods have different suitable applications. We have been focusing on the use of a hanging drop culture method for modeling various non-cancerous and cancerous diseases because this technique is affected only by gravity force and buoyant force and is thus the simplest method among the various single cell type-derived spheroid culture methods. We have found that the biological natures of spheroids generated even by the simplest method of hanging drop cultures are completely different from those of 2D cultured cells. In this review, we focus on the biological aspects of single cell type-derived spheroid culture and its applications in in vitro models for various diseases.

DOI： 10.3390/cells13181549

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Language：Japanese   Publisher：(一社)日本胆道学会  

Ichushi

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Introduction

To diagnose sinusoidal obstruction syndrome/veno‐occlusive disease (SOS/VOD), transabdominal ultrasonography is usually used to detect hemodynamic changes, but we tried to detect the changes using four‐dimensional computed tomography (4D‐CT). A 42‐year‐old Japanese woman was diagnosed with late‐onset SOS/VOD with transabdominal ultrasonography and was also assessed using 4D‐CT. Method We analyzed the portal vein (PV) contrast effect every 1.5 seconds and plotted the values of the contrast effect. With this graph, we analyzed three hemodynamic parameters.

Result

We found that these parameters correlated with the patient's status and indicated stasis due to sinusoid constriction.

Conclusion

4D‐CT may become a helpful tool to diagnose and follow up with SOS/VOD.

DOI： 10.1002/jha2.990

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

To elucidate the currently unknown molecular mechanisms responsible for the similarity and difference during the acquirement of resistance against gemcitabine (GEM) and paclitaxel (PTX) in patients with pancreatic carcinoma, we examined two-dimensional (2D) and three-dimensional (3D) cultures of parent MIA PaCa-2 cells (MIA PaCa-2-PA) and their GEM resistance cell line (MIA PaCa-2-GR) and PTX resistance (MIA PaCa-2-PR). Using these cells, we examined 3D spheroid configurations and cellular metabolism, including mitochondrial and glycolytic functions, with a Seahorse bio-analyzer and RNA sequencing analysis. Compared to the MIA PaCa-2-PA, (1) the formation of the 3D spheroids of MIA PaCa-2-GR or -PR was much slower, and (2) their mitochondrial and glycolytic functions were greatly modulated in MIA PaCa-2-GR or -PR, and such metabolic changes were also different between their 2D and 3D culture conditions. RNA sequencing and bioinformatic analyses of the differentially expressed genes (DEGs) using an ingenuity pathway analysis (IPA) suggested that various modulatory factors related to epithelial -mesenchymal transition (EMT) including STAT3, GLI1, ZNF367, NKX3-2, ZIC2, IFIT2, HEY1 and FBLX, may be the possible upstream regulators and/or causal network master regulators responsible for the acquirement of drug resistance in MIA PaCa-2-GR and -PR. In addition, among the prominently altered DEGs (Log2 fold changes more than 6 or less than -6), FABP5, IQSEC3, and GASK1B were identified as unique genes associated with their antisense RNA or pseudogenes, and among these, FABP5 and GASK1B are known to function as modulators of cancerous EMT. Therefore, the observations reported herein suggest that modulations of cancerous EMT may be key molecular mechanisms that are responsible for inducing chemoresistance against GEM or PTX in MIA PaCa-2 cells.

DOI： 10.3390/biomedicines12051011

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.annonc.2023.09.142

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Language：Japanese   Publisher：北海道医学会  

Ichushi

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

Ichushi

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Language：Japanese   Publisher：(一社)日本膵臓学会  

Ichushi

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

BACKGROUND: Histone deacetylase (HDAC) class I and IIa are highly expressed in hepatocellular carcinoma (HCC) and associated with decreased survival. However, clinically used pan and class I inhibitors have serious adverse events. In this study, we assessed the antitumor effects and tolerability of class IIa HDAC inhibitor (HDACI) with lenvatinib, which is a standard therapy for HCC. METHODS AND RESULT: Combination therapy with class IIa HDACI and lenvatinib exerted synergistic antitumor effect in human HCC cell lines. In mouse models, this therapy showed significant antitumor effects, and few adverse events occurred. In immunoblotting, the expression of fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) was high in cell lines that showed a high antitumor effect. In addition, class IIa HDACI administration decreased the expression of FGFR4. In the small interfering RNA (siRNA) analysis, knockdown of HDAC9, which is an isoform of HDAC class IIa, reduced the expression of FGFR4 and induced apoptosis. Immunohistochemistry of human clinical specimens showed a positivity rate of 32% for FGFR4 and 84% for HDAC9 in HCC, and all FGFR4-positive patients were HDAC9 positive. CONCLUSION: Class IIa HDACI and lenvatinib combination therapy induces apoptosis by downregulating FGFR4 and blocking the FGFR signaling in FGFR4-positive HCC cell lines and has demonstrated synergistic antitumor effects and safety. This combination therapy overcomes the problems of conventional therapies and will be beneficial for FGFR4-positive HCC patients.

DOI： 10.1007/s12072-023-10484-2

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BACKGROUND: Immune checkpoint inhibitors (ICIs) are the standard treatment for metastatic colorectal cancer (mCRC) with high microsatellite instability (MSI-H). Among immune-related adverse events (irAEs), drug-induced sarcoidosis-like reactions (DISR) are often difficult to differentiate from cancer progression. MAIN BODY: This is a case of a woman in her mid-60s, with mCRC (RAS wild/BRAF mutant/MSI-H) and abdominal lymph node metastasis, treated with four courses of ipilimumab + nivolumab every 3 weeks, followed by nivolumab every 2 weeks as third-line treatment. After treatment, the original lymph node metastases shrank, but hilar/mediastinal lymph nodes appeared. Endoscopic ultrasound-guided fine-needle aspiration of these lymph nodes revealed multiple epithelioid granulomas without necrosis, indicating a sarcoidosis-like reaction. Fluorodeoxyglucose-positron emission tomography scan showed abnormal subcutaneous accumulation in bilateral forearms and bilateral knee joints. Biopsy of the cutaneous lesions was also performed, which revealed epithelioid granulomas. As the patient had no symptoms in other organs, no specific therapeutic intervention was administered. After the discontinuation of immunotherapy, the sarcoidosis-like reaction regressed without cancer relapse. CONCLUSIONS: Clinicians should be aware of the possibility of DISR as an irAE during the ICI treatment of mCRC. In suspected cases of DISR following ICI therapy, it is important to differentiate between cancer progression and DISR through histological diagnosis for the subsequent strategy, as radiological and serological findings are not definitive.

DOI： 10.3389/fimmu.2023.1203621

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Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.0157-22

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Language：English  

Leukostasis is a life-threatening complication that causes vascular occlusion leading to organ damage in leukemia patients. Organs with impairment due to leukostasis are usually the lungs and kidneys, but other organs may also be damaged. We experienced an autopsy case of severe infarction in multiple organs including the spleen probably due to leukostasis in a patient with acute myeloid leukemia.

DOI： 10.7759/cureus.31518

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

Ichushi

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

Ichushi

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

Ichushi

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

Ichushi

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/iju5.12511

DOI： 10.1002/iju5.12511

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

We investigated the association between iron overload, oxidative stress (8-oxo-7,8-dihydroguanine: 8-oxo-dG scores), Wnt/β-catenin pathway activation (expression of glutamine synthetase: GS), and tumor hyperintensity in the Gd-EOB-DTPA-enhanced MRI hepatobiliary phase (relative enhancement ratio: RER). This was a retrospective analysis of 94 hepatocellular carcinoma (HCC) patients who underwent surgical resection. In HBV-, HCV-, and alcohol-associated HCC, serum ferritin levels in the high and low RER groups were equivalent. In contrast, ferritin levels were elevated in the 'high RER' group of patients with nonalcoholic fatty liver disease (NAFLD)-HCC. As predictors of GS positivity, high RER had a sensitivity of 57.2% and a specificity of 100%. High serum ferritin had a sensitivity of 85.7% and a specificity of 85.7%. All cases with serum ferritin ≥275.5 ng/mL and high RER were 8-oxo-dG- and iron staining-positive. Additionally, GS positivity was seen in all cases with "serum ferritin levels above the upper limits or iron staining-positive" and '8-oxo-dG high' cases. Therefore, combining serum ferritin levels with RER may increase the accuracy with which activated Wnt/β-catenin signaling is predicted in NAFLD-HCC. We suggest that 8-oxo-dG accumulates following increased oxidative stress due to hepatic tissue iron deposition; this may activate Wnt/β-catenin signaling and trigger carcinogenesis.

DOI： 10.3390/cancers14092066

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1346-8138.16331

DOI： 10.1111/1346-8138.16331

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.5337

DOI： 10.1002/ccr3.5337

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A 77-year-old man was referred to our hospital because of a hepatic tumor. Blood biochemistry showed elevated serum alfa-fetoprotein, protein induced by vitamin K absence-II, and carbohydrate antigen 19-9 levels. Gd-EOB-DTPA-enhanced magnetic resonance imaging revealed a 95-mm-sized tumor in liver S7. The tumor showed heterogeneous hyperintensity in the arterial phase, slightly washed out from the portal vein phase, and hypointensity in the hepatocellular phase. Post-enlargement segmental resection was performed, and the pathological diagnosis was combined hepatocellular cholangiocarcinoma. Seven months after surgery, multiple liver tumors were found, and biopsy revealed combined hepatocellular-cholangiocarcinoma. Hepatic arterial infusion chemotherapy with cisplatin was initiated. However, the patient developed a pulmonary abscess, which was treated with antibiotics. He then underwent treatment with lenvatinib, 11 months after surgery. At 8 weeks follow-up, a complete response (according to the modified Response Evaluation Criteria in Solid Tumors [RECIST]) and a partial response (RECIST version 1.1) was noted. To the best of our knowledge, thus far, only a single case of lenvatinib treatment of unresectable mixed liver cancer has been reported. In that case, lenvatinib was used as a third-line treatment. The present report is the first to describe lenvatinib as a first-line therapy for unresectable combined hepatocellular-cholangiocarcinoma, which resulted in a meaningful response. This case provides useful insights into the choice of appropriate drug treatment in this disease in the absence of randomized controlled trials of drug treatment.

DOI： 10.1159/000523895

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Other Link： http://www.nature.com/articles/s41598-021-83138-8

DOI： 10.1038/s41598-021-83138-8

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jgh3.12676

DOI： 10.1002/jgh3.12676

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Language：English   Publisher：(一社)日本血液学会  

Ichushi

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

Ichushi

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

Our pathological study of a case of poorly differentiated lymphocyte-rich hepatocellular carcinoma suggested that immune checkpoint inhibitor may be an effective therapy. The histological type is an important factor in determining treatment choices.

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.4764

DOI： 10.1002/ccr3.4764

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

DOI： 10.1016/j.oraloncology.2021.105287

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Amyloidosis is induced by extracellular deposition of certain proteins. Thirty-six proteins have so far been identified as amyloidogenic proteins in humans. Although it is very important to determine the specific amyloid protein type for the choice of therapy for amyloidosis patient, it might be difficult to identify specific proteins from amyloid-deposited tissue. Apolipoprotein A-IV is known as an amyloid-associated protein, but there have been few reports of apolipoprotein A-IV amyloidosis. Here we report a case of systemic apolipoprotein A-IV-associated amyloidosis that was confirmed by proteome analysis using formalin-fixed paraffin-embedded tissue and an immunohistochemical technique.

Other Link： http://link.springer.com/article/10.1007/s00428-021-03073-x/fulltext.html

DOI： 10.1007/s00428-021-03073-x

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

Ichushi

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.nut.2020.111093

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.3691

DOI： 10.1002/ccr3.3691

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Publishing type：Research paper (scientific journal)   Publisher：Spandidos Publications  

DOI： 10.3892/or.2021.7948

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

DOI： 10.1161/circimaging.120.010478

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Gastroenterological Endoscopy Society  

DOI： 10.11280/gee.62.785

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Other Link： https://link.springer.com/article/10.1007/s00277-020-04053-y/fulltext.html

DOI： 10.1007/s00277-020-04053-y

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Language：Japanese   Publisher：(一社)日本膵臓学会  

Ichushi

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Other Link： http://link.springer.com/article/10.1007/s13691-020-00405-7/fulltext.html

DOI： 10.1007/s13691-020-00405-7

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Language：Japanese   Publisher：日本消化器病学会-北海道支部  

Ichushi

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

The aim of the present study was to evaluate the survival impact of surgical resection among patients with pulmonary metastases from bone and soft tissue sarcomas. A total of 34 consecutive patients with ≤5 pulmonary metastases from bone and soft tissue sarcomas were retrospectively reviewed. The patients included 19 men and 15 women, with a median age of 64.0 years and a median follow-up of 14.5 months. The oncological outcome was compared between patients who underwent surgical and non-surgical treatment. A total of 22 patients underwent surgery and 12 patients did not undergo surgery. The surgery group had 3- and 5 year overall survival rates of 62 and 53%, respectively. None of the patients in the non-surgery group survived to 3 years. Compared with the non-surgery group, surgery achieved significantly better 3- and 5 year overall survival rates. Pulmonary metastasectomy was associated with significantly improved survival among patients who were aged <64 years (P=0.0155), as well as those who were aged ≥64 years (P=0.0444), which indicated that age was not associated with a difference in survival between the two groups. Therefore, pulmonary metastasectomy may improve the prognosis of patients with pulmonary metastases from bone and soft tissue sarcomas.

DOI： 10.3892/mco.2020.2009

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Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

<sec><title>Background:</title> Benzodiazepines (BZDs) and analgesics are widely used for conscious sedation during endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP). However, endoscopic procedures are sometimes discontinued because of BZD-induced disinhibitory reactions such as excessive movement. We evaluated the usefulness of dexmedetomidine (DEX) for BZD-induced disinhibition in ERCP.

</sec><sec><title>Methods:</title> Between February 2018 and August 2019, 22 patients who underwent EUS or ERCP were enrolled. All patients showed BZD-induced excessive movement at the first examination (BZD group) and received DEX at the second examination (DEX group). The initial DEX dose was 6 μg/kg/h for a 10-min loading, followed by 0.4 μg/kg/h during the procedure. BZDs and analgesics were administered before scope insertion. An additional sedative was administered to achieve a Ramsay sedation scale (RSS) of 4–5. Sedative effect, procedure completion rate, and changes in circulatory and respiratory dynamics were evaluated.

</sec><sec><title>Results:</title> Mean RSS scores were significantly higher ( p &lt; 0.001) in the DEX (5.1 ± 0.5) compared with the BZD (4.0 ± 0.5) group. The movement score ( p &lt; 0.001) and number of additional sedatives required ( p &lt; 0.01) were lower in the DEX group. The procedure completion rate was significantly higher in the DEX (95.5%) compared with the BZD group (63.6%; p &lt; 0.05). Significant differences in the frequency of hypotension ( p = 1.00), bradycardia ( p = 0.22), and respiratory depression ( p = 0.68) were not noted between groups.

</sec><sec><title>Conclusions:</title> The addition of DEX to BZD therapy yielded better sedative efficacy, lower excessive movement, a reduction in BZDs used, and a higher procedure complete rate. DEX may be used as an alternative method for BZD-induced inhibition during ERCP.

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Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/1756284820911822

DOI： 10.1177/1756284820911822

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Publishing type：Research paper (scientific journal)   Publisher：Hindawi Limited  

A 62-year-old Japanese female was referred to our hospital with gastrointestinal bleeding. Although small-bowel bleeding was suspected, no bleeding source was identified by enhanced computed tomography (CT), video capsule endoscopy (VCE), and double-balloon enteroscopy (DBE). Five years later, the patient had recurrent intermittent bloody stools with a significant decrease in hemoglobin levels. Although no active bleeding was observed on antegrade DBE, we detected a pulsatile submucosal uplift accompanied by a small red patch on the top of the uplift in the jejunum. Arteriovenous malformation (AVM) was suspected as the cause of small-bowel bleeding. Multiple-phase CT showed a number of small vascular ectasias during the arterial phase in the jejunum, and we confirmed the presence of multiple AVMs in the jejunum by selective angiography. To identify the location of the lesions and determine the minimal surgical margins, we performed intraoperative selective angiography with indocyanine green (ICG) injection. This technique allowed us to clearly observe the region and perform segmental small-bowel resection with minimal surgical margin. The patient reported that she has had no gastrointestinal bleeding at the two years follow-up visit.

Other Link： http://downloads.hindawi.com/journals/crim/2019/2046857.xml

DOI： 10.1155/2019/2046857

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

5‑Fluorouracil (5‑FU) is a cytotoxic anticancer drug commonly used for patients with advanced colon cancer. This drug effectively reduces the size of tumors to a certain degree; however, cancer cells can gradually acquire resistance, resulting in disease progression. To identify the mechanism of 5‑FU resistance, we established three 5‑FU‑resistant colon cancer cell lines and analyzed both apoptosis‑related protein expression levels and BH3 profiling. These 5‑FU‑resistant colon cancer cell lines acquired apoptotic resistance to 5‑FU. Although apoptosis‑related protein expression levels were altered in each 5‑FU‑resistant colon cancer cell line variably, BH3 profiling indicated BCLXL dependence in 5‑FU‑resistant HT‑29 cells only. Functional BCLXL inhibition in 5‑FU‑resistant HT‑29 cells not only sensitized the cells to apoptosis but also overcame 5‑FU resistance. The apoptotic BIM protein was preferentially sequestered, thereby resulting in acquired dependence on BCLXL for survival. Additionally, in vivo models showed that BCLXL inhibition controlled tumor progression. These results indicate that BH3 profiling facilitates the identification of the functional role of anti‑apoptotic proteins during drug resistance and has clinical implications for colon cancer in targeting specific proteins such as BCLXL.

DOI： 10.3892/or.2019.7373

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Language：Japanese   Publisher：北海道医学会  

Ichushi

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Language：English   Publisher：(一社)日本癌治療学会  

Ichushi

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.bcmd.2019.04.014

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00263&link_issn=&doc_id=20190806060002&doc_link_id=10.2957%2Fkanzo.60.294&url=https%3A%2F%2Fdoi.org%2F10.2957%2Fkanzo.60.294&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Ichushi

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

A 70-year-old woman developed severe buttock pain that progressed to a walking disturbance. Radiographs and computed tomography scans revealed an osteolytic lesion with osteosclerosis extending from the body to the arch of the fifth lumbar vertebra. Magnetic resonance imaging showed multinodular masses in the fifth lumbar vertebral body extending into the spinous processes and right transverse process. The masses were hypointense to isointense on T1-weighted images and hypointense to hyperintense on T2-weighted images. Histologic examination of biopsy specimens showed destruction of the trabecula of the vertebral bone by a fascicular and solid proliferation of spindle tumor cells and scattered rhabdomyoblasts, in a fibrotic background. The tumor cells were immunoreactive for keratins, vimentin, desmin, MyoD1, myogenin, and anaplastic lymphoma kinase. Fluorescence in situ hybridization detected split signals for FUS and TFCP2 in 80% and 64% of the tumor cells, respectively, suggesting FUS-TFCP2 fusion. Reverse transcription-polymerase chain reaction revealed a FUS-TFCP2 fusion. The final diagnosis was spindle cell rhabdomyosarcoma of a lumbar vertebra with a FUS-TFCP2 fusion. A spindle cell rhabdomyosarcoma with a FUS-TFCP2 fusion in a vertebral bone is rare and should be differentiated from metastatic carcinoma, particularly in the elderly.

DOI： 10.1016/j.prp.2019.03.027

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Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.2321-18

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Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Introduction: Liver transplantation for hepatocellular carcinoma (HCC) has been established as a curative therapy of underlying liver disease and cancer. However, the role of liver transplantation remains controversial for patients with HCC beyond Milan criteria. Case Presentation: A man in his 50s who was diagnosed as having two foci of HCC and advanced liver cirrhosis was referred to our hospital for further examination and treatment. Both foci of HCC were located in segment 8 of the liver and measured 39 and 9 mm. Endoscopy showed esophageal varices that had a high risk of bleeding. After endoscopic ligation of the esophageal varices, he underwent transcatheter arterial chemoembolization (TACE) for downstaging of the advanced HCCs. No further liver deterioration was observed after TACE, and HCC staging was successfully downstaged to within the Milan criteria. One hundred ten days after TACE, he underwent liver transplantation; at 2.5 years after transplantation, he remains alive without HCC recurrence. Discussion/Conclusion: There are only a few treatment options available for patients with advanced HCC and severe liver damage. Multidisciplinary treatment such as locoregional treatments and prophylaxis of variceal bleeding may result in tumor downstaging, enabling radical liver transplantation without further exacerbation of liver damage.

DOI： 10.1159/000499703

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society of Hepatology  

DOI： 10.2957/kanzo.60.294

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

We and others have demonstrated that various abnormalities of the bone marrow (BM) mesenchymal stromal cells (MSCs) such as aberrant cytokine expression, abnormal hedgehog signaling, and impaired miRNA biogenesis are observed in patients with acute myeloid leukemia (AML). However, underlying mechanisms to induce the dysfunction of BM MSCs have not yet been clarified. We previously showed that AML cells release abundant exosomal miR-7977, which, in turn, enters BM mesenchymal stromal cells (MSCs). However, the precise function of miR-7977 is not known. In this study, we performed transduction of a miR-7977 mimic into MSCs, compared transcriptomes between control-transduced (n = 3) and miR-7977-transduced MSCs (n = 3), and conducted pathway analysis. The array data revealed that the expression of 0.05% of genes was reduced 2-fold and the expression of 0.01% of genes was increased 2-fold. Interestingly, approximately half of these genes possessed a miR-7977 target site, while the other genes did not, suggesting that miR-7977 regulates the gene expression level directly and indirectly. Gene set enrichment analysis showed that the gene sets of Yes-associated protein 1 (YAP1) _up were significantly enriched (p<0.001, q<0.25), suggesting that miR-7977 modulates the Hippo-YAP signaling pathway. Visualization of pathway and network showed that miR-7977 significantly reduced the expression of Hippo core kinase, STK4. miR-7977 inactivated the Hippo-YAP signaling pathway as proven by GFP-tagged YAP nuclear trans localization and TEAD reporter assay. The miR-7977-transduced MSC cell line, HTS-5, showed elevated saturation density and enhanced entry into the cell cycle. These results suggest that miR-7977 is a critical factor that regulates the Hippo-YAP signaling pathway in BM-MSCs and may be involved in the upregulation of leukemia-supporting stroma growth.

DOI： 10.1371/journal.pone.0213220

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Background: Carcinoma ex pleomorphic adenoma (CXPA) is a rare histologic subtype of lacrimal gland and submandibular gland cancer. Currently, there is no standard treatment for metastatic CXPA, although some case reports have explored the role of targeted agents in chemotherapy. A few histopathologic analyses have shown that some of these tumors overexpress human epidermal growth factor receptor-2 (HER2), suggesting a potential role for HER2-based therapy. We report here two cases of metastatic CXPA that were treated with trastuzumab-based chemotherapy (IRB approved) with rapid and significant responses. Case Report 1: A 66-year-old male was diagnosed as HER2-positive CXPA of the right lacrimal gland with multiple bone and lymph node metastases. Combination chemotherapy with trastuzumab (Tmab) and nanoparticle albumin-bound paclitaxel (nabPTX) was initiated. A rapid response was confirmed, and after seven cycles of treatment, CR(complete response) was achieved. Case Report 2: A 67-year-old female was diagnosed with HER2 positive CXPA of the right submandibular gland. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with Tmab and nab-PTX was initiated. A rapid partial response (PR) was confirmed, and she eventually became disease-free. Conclusion: In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of HER2-positive CXPA, therapeutic information must be obtained from case reports. Some reports, such as this one, have suggested a potential utility of trastuzumab-based chemotherapy.

DOI： 10.1159/000495344

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Sapporo Medical University  

DOI： 10.15114/smj.87.35

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DOI： 10.1016/j.freeradbiomed.2018.09.010

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Language：English   Publisher：札幌医科大学  

Ichushi

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

DOI： 10.1016/j.jos.2018.11.002

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DOI： 10.1016/j.jdcr.2018.08.012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Impact Journals LLC  

DOI： 10.18632/oncotarget.25350

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Other Link： http://link.springer.com/content/pdf/10.1007/s13691-017-0308-8.pdf

DOI： 10.1007/s13691-017-0308-8

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Hepatic iron accumulation is generally increased in the chronic hepatitis C (CHC) liver; however, the precise mechanism of such accumulation remains unclear. We evaluated iron absorption from the gastrointestinal tract of patients with CHC and control participants. We measured the expression of a panel of molecules associated with duodenal iron absorption and serum hepcidin levels to determine the mechanism of iron accumulation in the CHC liver. We enrolled 24 patients with CHC and 9 patients with chronic gastritis without Helicobacter pylori infection or an iron metabolism disorder as control participants. An oral iron absorption test (OIAT) was administered which involved a dosage of 100 mg of sodium ferrous citrate. Serum level of hepcidin-25 was measured by liquid chromatography-tandem mass spectrometry. Ferroportin 1 (FPN) mRNA was measured by RT-PCR and FPN protein was analyzed by western blot. Samples were obtained from duodenum biopsy tissue from each CHC patient and control participant. Caco-2/TC7 cells were incubated in Costar transwells (0.4 μm pores). The OIAT showed significantly greater iron absorption in CHC patients than control participants. Serum hepcidin-25 in the CHC group was significantly lower than in the control group. Compared with control participants, duodenal FPN mRNA expression in CHC patients was significantly upregulated. The FPN mRNA levels and protein levels increased significantly in Caco-2/TC7 cell monolayers cultured in transwells with hepcidin. Lower serum hepcidin-25 levels might upregulate not only FPN protein expression but also mRNA expression in the duodenum and cause iron accumulation in patients with CHC.

DOI： 10.1155/2018/2154361

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Language：Japanese   Publisher：(一社)日本エイズ学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

PURPOSE: Triplet therapy using docetaxel, cisplatin, and S-1 (DCS) against unresectable gastric cancer as previously reported by us showed high clinical efficacy, with a 87.1% total response rate; however, it also showed a high incidence of grade 3/4 toxicity. With the aim of reducing toxicities, we conducted a phase II study of modified DCS (mDCS), using a reduced dose of docetaxel, and evaluated the clinical efficacy and adverse events of this regimen. METHODS: Patients with unresectable gastric cancer received chemotherapy with S-1 (40 mg/m2 b.i.d) on days 1-14, and docetaxel (50 mg/m2) plus cisplatin (60 mg/m2) on day 8 every 3 weeks. The primary endpoint was the response rate (RR). Overall (OS) and progression-free survival (PFS), and toxicities were also evaluated. RESULTS: Forty-nine patients were enrolled from November 2011 to April 2014, and 43 were eligible. The overall RR was 79.1%, including two cases of a complete response (4.7%), and 32 cases of a partial response (74.4%). Nine cases had stable disease (20.9%) but none showed progressive disease. Of the 43 cases, 15 cases (34.9%) underwent curative conversion surgery. The median PFS was 350 days (95% CI 240-416 days) and median OS was 722 days (95% CI 411 days-not reached). Grade 3/4 neutropenia developed in 79.1%, and febrile neutropenia in 34.9%, of patients. Non-hematological grade 3/4 adverse events were anorexia (25.6%), nausea (4.7%), and diarrhea (9.3%). CONCLUSION: Modified DCS therapy showed high clinical efficacy sufficient enough to attempt conversion therapy against unresectable gastric cancer. Modified DCS showed fewer toxicities, but careful management of these is still essential.

Other Link： http://link.springer.com/content/pdf/10.1007/s00280-017-3404-8.pdf

DOI： 10.1007/s00280-017-3404-8

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

A 64-year-old man was diagnosed with chronic-phase chronic myelogenous leukemia(CML)in May 2009. He was treated with imatinib and achieved complete cytogenetic response(CCyR)in 2 months. After 4 months of treatment, he developed interstitial pneumonia and became intolerant to imatinib. He was then switched to nilotinib from October of the same year. In June 2013, he was diagnosed with drug-induced pericarditis resulting from nilotinib use, and thus, nilotinib was discontinued. Subsequently, he was followed up without specific treatment for CML. In January 2014, he was admitted to the Dept. of Cardiovascular, Renal and Metabolic Medicine at our hospital because of heart failure. After examinations of cardiac function, he was diagnosed with constrictive pericarditis. Therefore, pericardiolysis was performed by the Dept. of Cardiovascular Surgery at our hospital. Pathologic findings showed hyaline-like fibrous tissue proliferation in the pericardium, which was diagnosed as fibrous pericarditis induced by nilotinib. We report a case of chronic myelogenous leukemia that developed fibrous pericarditis owing to nilotinib use.

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DOI： 10.1016/j.jiac.2016.12.008

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Language：Japanese   Publisher：日本骨髄腫学会  

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

<p>A 65-year-old man was admitted under emergency to our hospital because of abdominal pain. His current medication history did not include steroids or nonsteroidal antiinflammatory drugs. He had taken an eradication agent for <i>Helicobacter pylori</i>, and his serum was negative for <i>H. pylori</i> IgG antibody. Abdominal computed tomography indicated gastric perforation;therefore, emergency surgery was performed. Two weeks later, esophagogastroduodenoscopy revealed a gastric ulcer on the lesser curvature of the gastric angle and bezoars. The gastric perforation was thought to be caused by the bezoars. The bezoars were successfully treated with endoscopic therapy using Coca-Cola^®. The bezoars included over 98% tannin, and the patient had frequently consumed chestnuts. We thus diagnosed a rare case of gastric perforation caused by chestnut bezoars.</p>

DOI： 10.11405/nisshoshi.114.1830

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Gastroenterology  

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DOI： 10.1007/s00280-016-3163-y

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DOI： 10.1093/jnci/djw210

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DOI： 10.1093/jnci/djw038

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UNLABELLED: We report the treatment outcomes of 5 cases of adult-onset Ewing sarcoma(ES)managed between 2011 and 2014. We examined prognostic factors including the primary lesion, tumor size, metastatic status, and serum LDH levels. RESULTS: The locations of the primary lesions included the limbs in 1 case and the trunk in 4; the cases in the trunk had a worse prognosis than that in the limbs. Tumor size was greater than 8 cm in only 1 patient, who also displayed evidence of metastases at presentation and high LDH levels. All the patients received chemotherapy consisting of alternating vincristine, doxorubicin, and cyclophosphamide(VDC)and etoposide and ifosfamide(IE). Surgery was selected for the treatment of 4 patients, and radiotherapy was administered to 1 patient for local treatment of the tumor. A median follow-up duration of 31.6 months revealed the 2-year overall survival rate and progression-free survival rate to be 80.0%. CONCLUSIONS: The prognosis of patients with adult-onset ES is poor; however, combined modality therapy, including VDC-IE, was demonstrated to improve the outcome of patients in the present study. Nevertheless, the patient with tumor size exceeding 8 cm, metastasis, and high LDH levels, relapsed 1 year after treatment, as reported previously. Further investigation is required to clarify the factors affecting prognosis in adults, and to develop effective therapies for patients with a poor prognosis.

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Complete remission by induction therapy in acute myelogenous leukemia (AML) can be achieved due to improvements in supportive and optimized therapy. However, more than 20% of patients will still need to undergo salvage therapy, and most will have a poor prognosis. Determining the specificity of drugs to leukemia cells is important since this will maximize the dose of chemotherapeutic agents that can be administered to AML patients. In turn, this would be expected to lead to reduced drug toxicity and its increased efficacy. We targeted Notch-1 positive AML cells utilizing fucose-bound liposomes, since activation of Notch-1 is required for O-fucosylation. Herein, we report that intravenously injected, L-fucose-bound liposomes containing daunorubicin can be successfully delivered to AML cells that express fucosylated antigens. This resulted in efficient tumor growth inhibition in tumor-bearing mice and decreased proliferation of AML patient-derived leukemia cells. Thus, biological targeting by fucose-bound liposomes that takes advantage of the intrinsic characteristics of AML cells could be a promising new strategy for Notch-1 positive-AML treatment.

DOI： 10.18632/oncotarget.9558

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Language：Japanese   Publisher：(一社)日本神経学会  

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BACKGROUND: Systemic capillary leak syndrome is a rare condition characterized by episodic attacks of hypovolemia due to systemic capillary hyperpermeability, which results in profound hypotension and edema. Although the implication of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 has been suggested, the pathogenesis of systemic capillary leak syndrome remains unclear. In this report, we describe a case of systemic capillary leak syndrome in which serum isoform D of vascular endothelial growth factor was elevated. To the best of our knowledge, this is the first reported case of systemic capillary leak syndrome in which isoform D of vascular endothelial growth factor is suggested as the plausible biomarker. CASE PRESENTATION: A 41-year-old Japanese man was transferred to our emergency department. He was hypotensive, tachycardic, and edematous over the trunk and all four limbs. He received aggressive intravenous fluid therapy and underwent fasciotomy of the right forearm to prevent muscle necrosis. A diagnosis of systemic capillary leak syndrome was suspected. The presence of serum monoclonal immunoglobulin G and κ light chain supported this diagnosis. Prevention of hypotensive crises was unsuccessfully attempted with theophylline, intravenous immunoglobulin, high-dose dexamethasone, bortezomib, melphalan, and prednisolone; however, the patient's attacks dramatically disappeared after the introduction of thalidomide. The serum of the patient was stored soon after the onset of hypotensive crisis and analyzed to profile possible mediators responsible for the capillary leak. The concentration of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 were all within normal ranges. Meanwhile, we found that isoform D of vascular endothelial growth factor was elevated, which was normalized after the introduction of thalidomide. CONCLUSIONS: In our patient, isoform D of vascular endothelial growth factor (instead of vascular endothelial growth factor) may have been a causative factor of hypotensive crises, since isoform D contributes to vascular endothelial growth factor receptor-2 signaling, which is the major mediator of the permeability-enhancing effects of vascular endothelial growth factor. We suggest the measurement of isoform D of vascular endothelial growth factor in patients with systemic capillary leak syndrome in whose serum vascular endothelial growth factor is not elevated.

DOI： 10.1186/s13256-016-0894-7

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DOI： 10.3324/haematol.2015.134932

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DOI： 10.1371/journal.pone.0152823

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DOI： 10.11406/rinketsu.57.52

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J-GLOBAL

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DOI： 10.1007/s10120-014-0454-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Neurosurgical Society  

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. It is characterized by multiple xanthogranulomatous masses throughout the body, predominantly in the tibia. One of the characteristic radiological findings of the lesions associated with ECD is a "coated artery," which is often observed in the aorta. Although approximately one-fourth of ECD cases involve the central nervous system (CNS), an intracranial-coated artery has only been reported in four cases. We report a case of ECD that involves the CNS and has the unique appearance of a coated vertebral artery (VA). These tumors entirely encase the bilateral VAs without stenosis and are attached to the dura. Cranial magnetic resonance imaging also showed multiple extra-axial tumors in the cavernous sinus, the frontal convexity, and the orbital cavity. Further investigation revealed additional extracranial lesions around the cervical carotid artery, at the bilateral tibia, and at the elbow joint. A biopsy of the cervical and tibial lesions confirmed ECD. Steroid therapy resulted in a month-long improvement of preoperative symptoms. However, the patient's condition gradually progressed and he died of pneumonia 1 year after ECD diagnosis. The encasement of the intracranial artery by the tumor without stenosis and the dural attachment suggest ECD, which requires whole body investigation.

DOI： 10.2176/nmccrj.cr.2015-0331

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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DOI： 10.1007/s10147-015-0810-y

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Language：English   Publisher：Springer Japan  

Other Link： http://search.jamas.or.jp/link/ui/2017171943

DOI： 10.1007/s10120-015-0557-1

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DOI： 10.1002/hep.27774

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society of Hepatology  

DOI： 10.2957/kanzo.56.356

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

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DOI： 10.1007/s00280-014-2672-9

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DOI： 10.11405/nisshoshi.112.1664

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To date, intravenous drip infusion of zoledronic acid (ZA) has mainly been used for the treatment and prevention of skeletal-related events (SRE) in patients with multiple myeloma (MM). Recently, denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL), has also become available for the same purpose, but little is known about the impact of switching from ZA to denosumab. Herein, we present a retrospective study on bone metabolic markers in 10 MM patients initially treated with ZA and then switched to denosumab. Consequently, the levels of bone resorption markers, tartrate-resistant acid phosphatase 5b (TRACP-5b) and serum type-I collagen crosslinked N-telopeptide (sNTX), significantly decreased after denosumab treatment, while the levels of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), showed no apparent changes. No patient developed severe hypocalcemia with denosumab treatment. In one patient not given chemotherapy, the M-protein level increased after switching from ZA to denosumab and plateaued when ZA was restarted. Based on this finding, we anticipate that switching from ZA to denosumab would exert a stronger suppressive effect on osteoclasts, but the anti-myeloma activity of ZA must be taken into consideration.

Other Link： https://jlc.jst.go.jp/DN/JLC/20000648590?from=CiNii

DOI： 10.11406/rinketsu.55.2271

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Other Link： http://link.springer.com/article/10.1007/s12185-014-1652-5/fulltext.html

DOI： 10.1007/s12185-014-1652-5

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

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DOI： 10.1055/s-0034-1365526

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000368714

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Other Link： http://link.springer.com/article/10.1007/s12185-014-1530-1/fulltext.html

DOI： 10.1007/s12185-014-1530-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000366294

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000363100

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DOI： 10.1038/bcj.2014.2

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DOI： 10.1038/bjc.2013.699

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DOI： 10.2957/kanzo.55.162

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DOI： 10.11406/rinketsu.54.2053

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BACKGROUND: This retrospective study was carried out to compare computed tomographic (CT) gastrography and conventional optical gastroscopy (GS) in order to evaluate the effectiveness of chemotherapy in primary gastric lesions. METHODS: Patients with unresectable advanced and unresected early gastric cancer who had primary lesions and had received chemotherapy were enrolled. For primary lesions, CT gastrography and endoscopic assessment were done after chemotherapy, based on the Japanese Classification of Gastric Carcinoma (JCGC) criteria, 13th edition, and the Response Evaluation Criteria in Solid Tumors (RECIST). For metastatic solid lesions including lymph nodes, CT assessment was done based on the RECIST criteria. RESULTS: Data from 23 patients were analyzed. With median follow-up of 9.4 months (range 2-23 months), 58 examinations were assessed by GS and CT gastrography. Setting optical endoscopic results as the gold standard, the accuracy of CT gastrography for primary gastric lesions was 77.6 % (45 of 58) (weighted κ = 0.72; P < 0.01) according to the JCGC 13th edition criteria and 90.0 % (52 of 58) (weighted κ = 0.75; P < 0.01) according to the RECIST. When all results were divided into two groups [the non-progressive disease (non-PD) group and PD group], accuracy was 93.1 % (52 of 58) (κ = 0.81; P < 0.01), sensitivity was 100 %, and specificity was 75.0 % (12 of 16). In addition, the predictability of PD was 100 % (12 of 12). The four cases of failure in specification were the following: a case of gastric remnant cancer, a case with insufficient distension of the stomach, a healed case with stenosis and scarring, and a case in which the wrong position had been selected for the examination. The average period until PD was 9.9 months (range 5-18 months), and the concordance period between GS and CT gastrography was 7.2 months in both non-PD and PD cases. CONCLUSIONS: There was good concordance between the evaluations of GS and CT gastrography. CT gastrography exhibited favorable results in accuracy as well as 100 % PD predictability, which implied the possibility of using CT gastrography as a substitute for endoscopic assessments at post-chemotherapy assessments.

DOI： 10.1007/s10120-012-0217-7

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Other Link： http://link.springer.com/article/10.1007/s12328-013-0395-9/fulltext.html

DOI： 10.1007/s12328-013-0395-9

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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DOI： 10.1007/s00280-013-2073-5

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Ichushi

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DOI： 10.1038/bcj.2012.36

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DOI： 10.1097/MBC.0b013e32835510d6

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DOI： 10.1016/j.freeradbiomed.2012.06.006

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DOI： 10.1371/journal.pone.0039545

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DOI： 10.1007/s12185-012-1048-3

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Language：Japanese   Publisher：Japan Science and Technology Agency  

DOI： 10.1241/johokanri.54.674

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DOI： 10.2169/internalmedicine.51.7355

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DOI： 10.11405/nisshoshi.108.1405

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DOI： 10.1007/s12185-011-0881-0

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DOI： 10.1111/j.1872-034X.2011.00821.x

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DOI： 10.1007/s12185-011-0878-8

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Language：Japanese   Publisher：(株)響文社  

Ichushi

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A 76-year-old man presented with fever of unknown origin. Diagnostic imaging showed a liver tumor measuring 3cm in maximum dimension. The tumor was subsequently resected, and histopathology showed a moderately differentiated adenocarcinoma. This showed a number of bile ductules with variable amounts of stroma, well circumscribed but not encapsulated, so the lesion was diagnosed as a cholangiocarcinoma. Within the tumor there was also a cholangiolocarcinoma-like lesion. In addition, cystically dilated ductules resembling bile duct hamartoma and bile duct adenoma adjacent to the tumor were found, but with no area of transition among them. In the Glisson's capsule around the tumor, there was also a bile duct hamartoma.

DOI： 10.11405/nisshoshi.107.461

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Language：Japanese   Publisher：(一社)日本インターベンショナルラジオロジー学会  

Ichushi

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DOI： 10.1007/s00535-009-0089-8

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Language：Japanese   Publisher：(株)癌と化学療法社  

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A 65-year-old male, who had been diagnosed with melanoma of stage IIB and treated by chemotherapy since 2003 at the Dermatology Department, was referred to our department for liver metastasis of melanoma that had become resistant to chemotherapeutic agents. In 2006, he started receiving hepatic arterial infusion of CDDP. He was admitted to the hospital on an emergency basis for general fatigue the next May. Blood tests revealed anemia and thrombocytopenia. Contrast CT showed aggravation of liver metastasis. Contrast ultrasonography revealed nodular contrast enhancement at the margin of the tumor. On the basis of image findings and blood test results, DIC due to intratumoral hemorrhage was diagnosed. CDDP arterial infusion with DSM resulted in improved DIC, and he was able to be discharged. Taken together, attention has to be paid to the potential for emergency complications of DIC due to liver metastasis of melanoma with intratumoral hemorrhage. Moreover, it was shown that arterial infusion with DSM was effective for liver metastasis of melanoma.

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DOI： 10.1016/j.exphem.2008.04.007

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DOI： 10.1111/j.1872-034X.2007.00294.x

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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DOI： 10.1093/jjco/hyn015

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DOI： 10.1634/stemcells.2007-0741

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Language：Japanese   Publisher：(公社)日本超音波医学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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DOI： 10.1007/s00535-007-2095-z

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Language：Japanese   Publisher：(一財)日本消化器病学会  

Ichushi

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Language：Japanese   Publisher：(株)響文社  

Ichushi

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Language：Japanese   Publisher：(株)日本メディカルセンター  

Ichushi

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Language：Japanese   Publisher：(株)癌と化学療法社  

Ichushi

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：9  

A 59-year-old woman received eight cycles of R-CHOP for diffuse large B-cell lymphoma from July, 2004. Pretreatment HBV serological tests were positive, however, the transaminases were within normal limits, and she remained asymptomatic. Lamivudine (LAM) was administered orally from the start of R-CHOP. HBV-DNA levels gradually decreased and were not detected until December, 2004. LAM was administered until 3 months after the end of chemotherapy, with the entire treatment lasting less than 1 year. Two months after the cessation of treatment, she was re-admitted for general malaise. A liver function test revealed severe abnormalities, and HBVDNA levels were increased. Clinically, she was experiencing acute hepatitis due to HBV reactivation. She was then treated with LAM and interferon-beta immediately. Her HBV-DNA levels soon decreased, and liver function improved.

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A 70-year-old man was admitted for tranverse colon cancer with multiple liver metastases. Hepatic arterial infusion chemotherapy and systemic chemotherapy (FOLFOX 4) were conducted postoperatively. Thirteen months after the first surgery, liver metastases became resectable and hepatectomy was performed. Though multiple liver metastases were unresectable at the time of the first examination, hepatectomy was possible followed by hepatic arterial infusion chemotherapy and systemic chemotherapy.

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：8  

A 75-year-old man had been admitted to another hospital because of left abdominal pain, and was given a diagnosis of left hydronephrosis and acute pancreatitis. After a JJ stent insertion and medication, he was transferred to our hospital for further examinations. US and EUS revealed a chronic pancreatitis-like pattern and multicystic lesion in the pancreas head and body. At that time enhanced CT findings showed an extrapancreatic low density area to be inflammatory change, extending from the pancreas body to the left crus of the diaphragm and posteriorly the spreading from the left crus of the diaphragm via the left urinary duct into the left iliopsoas muscle, in which MRI revealed partial high intensity. ERCP and MRCP showed focal irregular narrowing of the pancreatic duct of unknown cause, and we decided that an internal pancreatic fistula due to pancreatitis had induced left ureteral obstruction, caused by a protein plug or alcohol. Follow-up 6 months later showed that extrapancreatic spreading of the low density area had markedly regressed without any change in the ureteral obstruction.

DOI： 10.11405/nisshoshi.104.1236

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DOI： 10.1016/j.exphem.2007.03.005

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DOI： 10.1158/1535-7163.MCT-06-0684

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：3  

A 78-year-old man had been admitted to a previous hospital because of epigastralgia and a diagnosis of cholecystolithiasis had been made. He had been transferred to our institution for further examination. CT scan and US revealed chronic cholecystitis and gallstone, however, ERC revealed severe obstruction of the cystic duct and EUS revealed dilation of that duct and a solitary mass there. Carcinoma of the cystic duct was diagnosed, and we performed cholecystectomy and resection of the extrahepatic duct with two-field lymphadenectomy. The pathological specimen showed a round flat elevated mass localized in the cystic duct. Histopathologically, the diagnosis was well differentiated tubular adenocarcinoma of the cystic duct with limy bile and tiny gallstone.

DOI： 10.11405/nisshoshi.104.394

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DOI： 10.1136/gut.2005.070417

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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Language：Japanese   Publisher：(公社)日本超音波医学会  

Ichushi

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Language：Japanese   Publisher：(株)響文社  

Ichushi

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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Language：Japanese   Publisher：(一財)日本消化器病学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本内科学会  

Ichushi

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DOI： 10.1016/j.exphem.2005.10.007

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Language：English   Publisher：The Japanese Society of Internal Medicine  

A 31-year-old man referred to our hospital for treatment of his chronic myeloid leukemia (CML) in the first chronic phase by bone marrow transplantation. We pretreated him with cyclophosphamide and total body irradiation and bone marrow transplantation (BMT) was carried out. On day 31, the engraftment was confirmed and on day 52, acute graft versus host disease (GVHD) was observed. On day 189, he lost consciousness due to cyclosporine A-induced leukoencephalopathy and 375 mg cyclosporine A was changed to 100 mg prednisolone. On day 199, liver dysfunction (AST 410 IU/L, ALT 557 IU/L, γGTP 385 IU/L, ALP 363 IU/L, D-Bil 0.3 mg/dl) developed and a liver biopsy was performed. PCR analysis of DNA from the liver biopsy specimen was positive for HHV-6 and immunostaining using anti-HHV-6 and anti-HHV-6b antibodies showed positive staining in the cytosol of hepatocytes. No other viruses were found to induce hepatitis. From these results, he was diagnosed as having HHV-6 hepatitis and it was successfully treated with gancyclovir (GCV) administration.<br>

Other Link： http://search.jamas.or.jp/link/ui/2007232367

DOI： 10.2169/internalmedicine.45.1507

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Ichushi

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DOI： 10.1002/ajh.20141

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DOI： 10.1097/00042737-200401000-00015

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DOI： 10.1007/s002700000381

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DOI： 10.1111/pin.12503

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Language：Japanese   Publisher：(一社)日本肝臓学会  

DOI： 10.2957/kanzo.56.584

Ichushi

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Language：Japanese   Publisher：日本骨髄腫学会  

Ichushi

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Language：English   Publishing type：Research paper, summary (international conference)  

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Language：Japanese   Publisher：日本臨床外科学会  

Ichushi

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Language：Japanese   Publisher：日本医療薬学会  

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Language：Japanese   Publisher：The Japanese Society of Hematology  

To date, intravenous drip infusion of zoledronic acid (ZA) has mainly been used for the treatment and prevention of skeletal-related events (SRE) in patients with multiple myeloma (MM). Recently, denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL), has also become available for the same purpose, but little is known about the impact of switching from ZA to denosumab. Herein, we present a retrospective study on bone metabolic markers in 10 MM patients initially treated with ZA and then switched to denosumab. Consequently, the levels of bone resorption markers, tartrate-resistant acid phosphatase 5b (TRACP-5b) and serum type-I collagen crosslinked N-telopeptide (sNTX), significantly decreased after denosumab treatment, while the levels of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), showed no apparent changes. No patient developed severe hypocalcemia with denosumab treatment. In one patient not given chemotherapy, the M-protein level increased after switching from ZA to denosumab and plateaued when ZA was restarted. Based on this finding, we anticipate that switching from ZA to denosumab would exert a stronger suppressive effect on osteoclasts, but the anti-myeloma activity of ZA must be taken into consideration.

DOI： 10.11406/rinketsu.55.2271

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：日本医療薬学会  

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Language：Japanese   Publisher：The Japan Society of Hepatology  

We report rare case of double cholangiolocellular carcinoma (CLC) and hepatocellular carcinoma complicated with non-alcoholic steatohepatitis (NASH). A 68-years old female with NASH was admitted to the hospital for examination and treatment of multiple hepatic tumors. Gd-EOB-DTPA enhanced MRI showed that tumor was located in segment 3, segment 4, and segment 6. The angiography and CT during angiography showed additional three tumors in segment 1 and segment 6. These tumors might be different tumor origin because of different imaging pattern. Operation was performed in segment 3 and 4, and RFA was performed in segment 1 and 6 because these tumors were diagnosed as hepatocellular carcinoma. Whitish tumor with clear margin which has no fibrous capsule was seen in tumor in segment 3. Pathologically, tumor in segment 3 showed CLC. Tumor in segment 4 was diagnosed as dysplastic nodule.

DOI： 10.2957/kanzo.53.615

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Language：Japanese   Publisher：日本医療薬学会  

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

DOI： 10.11405/nisshoshi.108.1405

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Language：English   Publishing type：Research paper, summary (international conference)  

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

A 76-year-old man presented with fever of unknown origin. Diagnostic imaging showed a liver tumor measuring 3cm in maximum dimension. The tumor was subsequently resected, and histopathology showed a moderately differentiated adenocarcinoma. This showed a number of bile ductules with variable amounts of stroma, well circumscribed but not encapsulated, so the lesion was diagnosed as a cholangiocarcinoma. Within the tumor there was also a cholangiolocarcinoma-like lesion. In addition, cystically dilated ductules resembling bile duct hamartoma and bile duct adenoma adjacent to the tumor were found, but with no area of transition among them. In the Glisson's capsule around the tumor, there was also a bile duct hamartoma.

DOI： 10.11405/nisshoshi.107.461

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Language：English   Publishing type：Research paper, summary (international conference)  

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Language：Japanese  

Other Link:： http://search.jamas.or.jp/link/ui/2008321841

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Language：English   Publishing type：Research paper, summary (international conference)  

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

A 75-year-old man had been admitted to another hospital because of left abdominal pain, and was given a diagnosis of left hydronephrosis and acute pancreatitis. After a JJ stent insertion and medication, he was transferred to our hospital for further examinations. US and EUS revealed a chronic pancreatitis-like pattern and multicystic lesion in the pancreas head and body. At that time enhanced CT findings showed an extrapancreatic low density area to be inflammatory change, extending from the pancreas body to the left crus of the diaphragm and posteriorly the spreading from the left crus of the diaphragm via the left urinary duct into the left iliopsoas muscle, in which MRI revealed partial high intensity. ERCP and MRCP showed focal irregular narrowing of the pancreatic duct of unknown cause, and we decided that an internal pancreatic fistula due to pancreatitis had induced left ureteral obstruction, caused by a protein plug or alcohol. Follow-up 6 months later showed that extrapancreatic spreading of the low density area had markedly regressed without any change in the ureteral obstruction.

DOI： 10.11405/nisshoshi.104.1236

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Language：Japanese  

A 47-year-old woman was admitted to our hospital in December 1994 with polycythemia. The patient's red blood cell volume was 33 ml/kg and bone marrow cytology was able to rule out other myeloproliferative diseases such as chronic myelogenous leukemia, essential thrombocytosis and myelofibrosis. The patient was diagnosed as having polycythemia vera. She had undergone only phlebotomy until 1999 when the thrombocytosis appeared, subsequent to which she was treated with oral hydroxyurea. However, in March 2006, she developed upper abdominal pain and was admitted to our hospital on March 14th, 2006. Computed tomography scan revealed thromboses in the portal and superior mesenteric veins. Anticoagulation therapy delivered intravenously via the superior mesenteric vein dramatically improved her symptoms and liver function. She is currently on anticoagulation therapy in our outpatient clinic.

DOI： 10.11406/rinketsu.48.554

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

A 78-year-old man had been admitted to a previous hospital because of epigastralgia and a diagnosis of cholecystolithiasis had been made. He had been transferred to our institution for further examination. CT scan and US revealed chronic cholecystitis and gallstone, however, ERC revealed severe obstruction of the cystic duct and EUS revealed dilation of that duct and a solitary mass there. Carcinoma of the cystic duct was diagnosed, and we performed cholecystectomy and resection of the extrahepatic duct with two-field lymphadenectomy. The pathological specimen showed a round flat elevated mass localized in the cystic duct. Histopathologically, the diagnosis was well differentiated tubular adenocarcinoma of the cystic duct with limy bile and tiny gallstone.

DOI： 10.11405/nisshoshi.104.394

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Language：English   Publishing type：Research paper, summary (international conference)  

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Language：Japanese   Publisher：The Japan Society of Hepatology  

DOI： 10.2957/kanzo.47.304

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Language：Japanese   Publisher：The Japan Society of Hepatology  

We report a 77-year-old man was admitted to our institution because of stage III hepatocellular carcinoma (HCC) and HCV-positive liver cirrhosis. Following transarterial chemoembolization (TAE) and radiofrequency ablation (RFA) was performed. 18 months after the first therapy, slight elevation of serum AFP level was pointed out and a metastatic lesion of the left adrenal gland was detected by computed tomography (CT). Another examinations were helpful in diagnosing the tumor as adrenal metastasis of HCC. He wished to be orally administered of UFT (300mg/day) at first, and followed three times TAI (transcatheter arterial chemoinfusion) to some feeding artery was performed, but that lesion had poor tumor stain. A further 5 months later, the tumor keeping progressive, systemic chemotherapy (FP) was carried out. The FP therapy consisted of 5-FU (500mg/body/day on day 1 to day 7/week, continuous infusion) and CDDP (10mg/body/day in 250ml normal saline, infusion for 2 hours, on day 1 and 4/week) for 2 consecutive weeks with a subsequent one-week rest period. After 2 cycles of systemic chemotherapy, adrenal metastasis was no change and lung metastases were regressed. But serum AFP level was additionally elevated, radiotherapy (40Gy/16f) was additively performed. After 5 cycles of combined therapy, adrenal metastasis was markedly regressed and lung metastases were not detectable.

DOI： 10.2957/kanzo.47.258

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Language：Japanese   Publisher：The Japan Society of Hepatology  

DOI： 10.2957/kanzo.47.245

Ichushi

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Language：English   Publishing type：Research paper, summary (international conference)  

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DOI： 10.2958/suizo.20.387

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

DOI： 10.11405/nisshoshi.102.888

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

DOI： 10.11405/nisshoshi.102.459

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

DOI： 10.11405/nisshoshi.102.453

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

DOI： 10.11405/nisshoshi.102.332

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Language：Japanese   Publisher：The Japan Society of Hepatology  

DOI： 10.2957/kanzo.46.208

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Language：English   Publishing type：Research paper, summary (international conference)  

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

DOI： 10.11405/nisshoshi.101.616