Junji Suzumiya

Shimane University, Matsu, Shimane, Japan

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Publications (236)878.15 Total impact

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    ABSTRACT: All-trans retinoic acid (ATRA) is valuable in differentiation therapy for acute promyelocytic leukemia (APL). However, ATRA has had limited success as a single agent, due to the development of resistance. We found that tamoxifen effectively enhanced the differentiation-inducing effect of ATRA. Tamoxifen alone inhibited the proliferation of myeloid leukemia cell lines while only slightly increasing morphologic differentiation. Tamoxifen effectively enhanced the growth-inhibiting actions of various differentiation-inducing agents. ATRA in the presence of tamoxifen increased NBT reduction and the expression of CD11b in HL-60 cells more effectively than ATRA alone. Tamoxifen also enhanced the differentiation induced by the other inducers tested. ATRA induced the differentiation of APL cell lines NB4 and HT93 and APL cells in primary culture, and this differentiation was also enhanced by tamoxifen. Tamoxifen is one of the most widely used drugs for the treatment of cancer and has few side effects. The combination of ATRA and tamoxifen might be considered for the treatment of APL patients in whom it can be difficult to apply arsenic trioxide or anthracyclines.
    No preview · Article · Jan 2016 · International Journal of Oncology
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    ABSTRACT: Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature T-lymphocytes caused by human T-lymphotropic virus type I (HTLV-1). Intensive combination chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) have been introduced since the previous Japanese nationwide survey performed in the late 1980s. In this study, we delineated the current features and management of ATL in Japan. The clinical data were collected retrospectively from the medical records of patients diagnosed with ATL between 2000 and 2009, and a total of 1665 patients' records were submitted to the central office from 84 institutions in Japan. Seventy-one patients were excluded, and finally 895, 355, 187, and 157 patients with acute, lymphoma, chronic, and smoldering types ATL remained, respectively. The median survival times (MST) were 8.3, 10.6, 31.5, and 55.0 months, and 4-year overall survival (OS) rates were 11%, 16%, 36%, and 52% for acute, lymphoma, chronic, and smoldering types, respectively. The number of patients with allo-HSCT was 227, and their MST and OS at 4 years after allo-HSCT were 5.9 months and 26%, respectively. This study revealed that the prognoses of the patients with acute and lymphoma types were still unsatisfactory despite the recent progress in treatment modalities, but an improvement of 4-year OS was observed in comparison to the previous survey. Of note, one-quarter of patients who could undergo transplantation experienced long survival. It is also an impact that the prognosis of the smoldering type was worse than it has been expected.
    No preview · Article · Sep 2015 · Blood

  • No preview · Article · Jun 2015 · Pancreatology
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    ABSTRACT: Although progress has been made in chemotherapeutic strategies against pancreatic cancer, overall survival has not significantly improved over the past decade. Thus, the development of better therapeutic regimens remains a high priority. Pancreatic cancer cell lines were treated with tamoxifen, a novel antitumor fusicoccin derivative (ISIR-042), and anticancer drugs, and their effects on cell growth, signaling and gene expression were determined. Xenografts of Panc-1 cells were treated with tamoxifen, ISIR-042 and 5-fluorouracil (5FU) to determine the effects on tumor growth. The inhibition of the growth of pancreatic cancer cells induced by tamoxifen was effectively reduced by α-tocopherol, a membrane stabilizer. ISIR-042 produced synergistic effects with tamoxifen in inhibiting cell growth. Tamoxifen elevated lipid peroxidation and the release of cytochrome c, and these effects of tamoxifen were reduced by α-tocopherol. ISIR-042 significantly inhibited colony formation and the expression of stemness-related genes of pancreatic cancer cells. The triple combination of tamoxifen, ISIR-042, and 5FU or gemcitabine was effective at inhibiting cell growth and the appearance of drug-resistant cells. This combined treatment significantly inhibited the growth of Panc-1 cells as xenografts without apparent adverse effects. The triple combination of tamoxifen and ISIR-042 with 5FU or gemcitabine may be highly effective against pancreatic cancer by overcoming resistance to therapy.
    No preview · Article · Apr 2015 · International Journal of Oncology
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    ABSTRACT: We sought to clarify the role of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) to treat blastic plasmacytoid dendritic cell neoplasm (BPDCN). We retrospectively identified 25 BPDCN patients (allo-HSCT, N = 14; auto-HSCT, N = 11) from registry data of the Japan Society for Hematopoietic Cell Transplantation and analyzed clinicopathological data and clinical outcomes after transplantation. The median age at HSCT was 58 (range, 17-67) years. All 11 patients who underwent auto-HSCT were in the first complete remission (CR1). With a median follow-up of 53.5 months, the overall survival rates at 4 years for patients who underwent auto-HSCT and allo-HSCT were 82% and 53% (P = 0.11), respectively, and progression-free survival rates were 73% and 48% (P = 0.14), respectively. Auto-HSCT for BPDCN in CR1 appears to provide promising results and deserves further evaluation in the setting of prospective trials. Copyright © 2015 American Society of Hematology.
    Full-text · Article · Apr 2015 · Blood
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    ABSTRACT: Objective Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of some anti-cancer drugs. However, medical staff frequently encounter difficulties in ascertaining the severity of CIPN. We sought to develop a questionnaire in order to accurately assess CIPN. The validity of this questionnaire was compared with that of free-style interviews. Methods We developed the CIPN self-check sheet by analyzing existing self-assessment tools for CIPN and matching the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grades. From August to December 2011, 77 cancer patients participated in this study. In order to evaluate the validity of the CIPN self-check sheet compared with a free-style interview assessment, the cross-classification and κ coefficients between the CTCAE grades from each assessment and those from a comprehensive assessment were analyzed. The comprehensive assessment utilized information obtained from the medical examination, free-style interview and CIPN self-check sheet. Results Upon completion of the study, 248 CIPN self-check sheets were collected (median number of sheets per patient, 3; range, 1-14). The cross-classification analysis illustrated that the CIPN self-check sheet successfully identified all grade 3 cases. The coefficient of the CIPN self-check sheet was significantly higher than that of the free-style interviews [κ values: 0.988 (p<0.01) and 0.501 (p<0.01) for the self-check sheet and interviews, respectively]. Conclusion The CIPN self-check sheet can be used to assess the severity of CIPN based on the CTCAE grade more accurately than free-style interviews.
    Preview · Article · Apr 2015 · Internal Medicine
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    ABSTRACT: Multiple myeloma is a malignant proliferative disease of plasma cells in the bone marrow and remains largely incurable. Cotylenin A, a fusicoccane diterpene glycoside with a complex sugar moiety, was isolated as a plant-growth regulator. Cotylenin A has been shown to inhibit the growth of various cancer cells. Herein, we examined the anti-myeloma effects of cotylenin A using five human myeloma cell lines (RPMI-8226, KMS-11, KMS-26, KMS-12 PE and KMS-12 BM) and xenografts in immunodeficient mice. Cotylenin A and vincristine synergistically inhibited the growth and induced apoptosis in myeloma cells. While other microtubule-disturbing agents also showed co-operative effects with cotylenin A, other anticancer agents, such as doxorubicin, cisplatin, camptothecin, methotrexate, gemcitabine and 5-fluorouracil, did not show such co-operation with cotylenin A. These differences might be attributed to the effects on autophagic responses. Combined treatment with cotylenin A and vincristine induced autophagy (formation of LC3-II and degradation of p62 protein). However, doxorubicin did not enhance the autophagy induced by cotylenin A. A colony-forming assay indicated that the combined treatment with cotylenin A and vincristine more effectively suppressed the formation of large colonies, which have higher self-renewal activity than vincristine alone. Expression of pluripotency-associated transcription factor Sox2 mRNA in RPMI-8226 myeloma cells was significantly suppressed by treatment with cotylenin A. Combined treatment with cotylenin A and vincristine significantly inhibited the growth of KMS-26 myeloma cells as xenografts. Our results suggest that the combination of cotylenin A and vincristine may have therapeutic value. Recently, it was reported that cotylenin A modulates the 14-3-3 intracellular signaling pathway. The 14-3-3 proteins may be novel targets in treating myeloma.
    No preview · Article · Feb 2015 · International Journal of Oncology
  • Yumi Jo · Junji Suzumiya

    No preview · Article · Feb 2015 · Nippon rinsho. Japanese journal of clinical medicine
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    ABSTRACT: A 61-year-old Japanese woman presented with hemophagocytic syndrome (HPS) and suffered from intravascular large B-cell lymphoma (IVLBCL). After a few days of supportive care, her condition improved without any anti-cancer drugs or steroids. She experienced recurrences of HPS at 15 mon and 21 mon after first presentation, but lymphoma cells were not observed. Relapse of IVLBCL with pulmonary involvement occurred 27 mon after first presentation. She underwent R-CHOP therapy followed by autologous stem cell transplantation. She is currently alive and without lymphoma. Immunostaining by anti-ssDNA suggested that spontaneous regression may have been due to apoptosis of the lymphoma cells. [J Clin Exp Hematop 55(3) : 151-156, 2015]
    Full-text · Article · Jan 2015 · Journal of Clinical and Experimental Hematopathology
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    ABSTRACT: The optimal treatment strategy with the use of hematopoietic stem cell transplantation (HSCT) for relapsed and refractory Hodgkin lymphoma (HL) remains unclear. We performed a retrospective analysis using registry data from the Japanese Society for Hematopoietic Cell Transplantation. Adult patients with HL who underwent a first autologous or a first allogeneic HSCT between 2002 and 2009 were included. Patients who underwent HSCT in first complete remission (CR) were excluded. Autologous and allogeneic HSCT were performed in 298 and 122 patients, respectively. For autologous HSCT, overall survival at 3 years (3yOS) was 70%, and sex, age, disease status, and performance status (PS) at HSCT were prognostic factors. OS was favorable even in patients who underwent autologous HSCT in disease status other than CR. For allogeneic HSCT, 3yOS was 43%, and sex and PS at HSCT were prognostic factors. Disease status at HSCT, previous autologous HSCT, and conditioning intensity did not affect OS. Moreover, graft-versus-host disease did not affect progression-free survival or relapse/progression rate. A first allogeneic HSCT without a previous autologous HSCT was performed in 40 patients. 3yOS was 45%, and was significantly inferior to that in patients who underwent their first autologous HSCT. This result was retained after the correction by the different patient characteristics according to the type of HSCT. In conclusion, autologous HSCT is effective in prolonging survival in patients with relapsed and refractory HL. Allogeneic HSCT might be beneficial even to relapsed HL after autologous HSCT, although establishing the role of allogeneic HSCT remains a challenge.
    No preview · Article · Nov 2014 · American Journal of Hematology
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    ABSTRACT: To evaluate haematopoietic stem cell transplantation (HSCT) in children and adolescents, we reviewed the records of 47 patients who were ≤18 years, had relapsed or refractory anaplastic large cell lymphoma, and received HSCT between 1990 and 2010. At HSCT, complete remission (CR) was less common in allogeneic HSCT recipients (n = 24) than in autologous HSCT recipients (n = 23) (P = 0·01). The autologous and allogeneic HSCT groups differed in terms of 5-year event-free survival (EFS) (38% vs. 50%, P = 0·63), cumulative incidence of progress or relapse (49% vs. 28%, P = 0·25), and treatment-related mortality (12% vs. 25%, P = 0·40). However, these differences were not significant. Patients with non-CR at autologous HSCT had a significantly lower EFS rate (14% vs. 48%, P = 0·03). Conversely, although those with non-CR at allogeneic HSCT had a lower EFS rate, this was not significant (44% vs. 63%, P = 0·26). Reduced-intensity conditioning regimens were used for three of the 16 allogeneic HSCTs received by patients with non-CR. These three patients achieved CR, surviving 32–65 months after HSCT. These results demonstrated that allogeneic HSCT might be a treatment option for patients who do not achieve CR through conventional chemotherapy.
    No preview · Article · Oct 2014 · British Journal of Haematology
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    ABSTRACT: Internal tandem duplication mutations in the Flt3 gene (ITD-FLT3) enhance cell migration toward the chemokine Cxcl12, which is highly expressed in the therapy-protective bone marrow niche, providing a potential mechanism underlying the poor prognosis of ITD-FLT3+ acute myeloid leukemia. We aimed to investigate the mechanisms linking ITD-FLT3 to increased cell migration toward Cxcl12. Classification of the expression of Cxcl12-regulated genes in ITD-FLT3+ cells demonstrated that the enhanced migration of ITD-FLT3+ cells toward Cxcl12 was associated with the differential expression of genes downstream of Cxcl12/Cxcr4, which are functionally distinct from those expressed in ITD-FLT3− cells but are independent of the Cxcr4 expression levels. Among these differentially regulated genes, the expression of Rock1 in the ITD-FLT3+ cells that migrated toward Cxcl12 was significantly higher than in ITD-FLT3− cells that migrated toward Cxcl12. In ITD-FLT3− cells, Rock1 expression and Mypt1 phosphorylation were transiently up-regulated but were subsequently down-regulated by Cxcl12. In contrast, the presence of ITD-FLT3 blocked the Cxcl12-induced down-regulation of Rock1 and early Mypt1 dephosphorylation. Likewise, the FLT3 ligand counteracted the Cxcl12-induced down-regulation of Rock1 in ITD-FLT3− cells, which coincided with enhanced cell migration toward Cxcl12. Rock1 antagonists or Rock1 shRNA abolished the enhanced migration of ITD-FLT3+ cells toward Cxcl12. Our findings demonstrate that ITD-FLT3 increases cell migration toward Cxcl12 by antagonizing the down-regulation of Rock1 expression. These findings suggest that the aberrant modulation of Rock1 expression and activity induced by ITD-FLT3 may enhance acute myeloid leukemia cell chemotaxis to the therapy-protective bone marrow niche, where Cxcl12 is abundantly expressed.
    Preview · Article · Sep 2014 · Journal of Biological Chemistry
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    Dataset: 2403738a
    K Ohshima · J Suzumiya · Y Guo · K Karube · T Yamaguchi · R Kawano · G-S Huang

    Full-text · Dataset · Mar 2014
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    Dataset: 2403738a
    Y Guo · T Yamaguchi · K Karube · J Suzumiya · G-S Huang · R Kawano · K Ohshima

    Full-text · Dataset · Mar 2014
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    ABSTRACT: CC chemokine receptor 4 (CCR4) is expressed by peripheral T-cell lymphomas (PTCLs) and is associated with poor outcomes. Mogamulizumab (KW-0761) is a defucosylated humanized anti-CCR4 antibody engineered to exert potent antibody-dependent cellular cytotoxicity. This multicenter phase II study evaluated the efficacy and safety of mogamulizumab in patients with relapsed PTCL and cutaneous T-cell lymphoma (CTCL). Mogamulizumab (1.0 mg/kg) was administered intravenously once per week for 8 weeks to patients with relapsed CCR4-positive PTCL or CTCL. The primary end point was the overall response rate, and the secondary end points included safety, progression-free survival (PFS), and overall survival (OS). A total of 38 patients were enrolled, and 37 patients received mogamulizumab. Objective responses were noted for 13 of 37 patients (35%; 95% CI, 20% to 53%), including five patients (14%) with complete response. The median PFS was 3.0 months (95% CI, 1.6 to 4.9 months), and the median OS was not calculated. The mean maximum and trough mogamulizumab concentrations (± standard deviation) after the eighth infusion were 45.9 ± 9.3 and 29.0 ± 13.3 μ g/mL, respectively. The most common adverse events were hematologic events, pyrexia, and skin disorders, all of which were reversible and manageable. Mogamulizumab exhibited clinically meaningful antitumor activity in patients with relapsed PTCL and CTCL, with an acceptable toxicity profile. Further investigation of mogamulizumab for treatment of T-cell lymphoma is warranted.
    Preview · Article · Mar 2014 · Journal of Clinical Oncology
  • Tsutomu Takahashi · Junji Suzumiya
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    ABSTRACT: Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) is a B-cell tumor thought to originate from B-lymphocytes that are normally present in the marginal zone of lymphoid follicles of the lymphoid tissue. About 50% of MALT lymphoma occurs in gastrointestinal tract. The majority of patients present with localized disease and indolent clinical progression. In localized gastric MALT lymphoma with Helicobacter pylori (HP) infection, HP eradication is recommended as first line therapy. In those without HP infection and localized non-gastric MALT lymphoma, involved field radiation therapy(IFRT) is recommended as first line therapy. Patients in advanced stage and salvage setting are managed according to the recommendations for advanced follicular lymphoma. The long-term survival rate of MALT lymphoma patients is 80-90%.
    No preview · Article · Mar 2014 · Nippon rinsho. Japanese journal of clinical medicine
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    ABSTRACT: The number of elderly patients with diffuse large B-cell lymphoma (DLBCL) continues to increase but the data of autologous stem cell transplantation (ASCT) for elderly patients are limited. We analyzed 484 patients aged 60 years or over diagnosed with relapsed/refractory DLBCL who received ASCT from 1993 to 2010 in the Japan Society for Hematopoietic Cell Transplantation database. Median age was 64 years (range: 60-78). To evaluate the impact of age at ASCT, patients were classified into three groups those aged 60 to 64, 65 to 69, and 70 years or over. Overall non-relapse mortality (NRM) at day 100, one year and two years was 4.1%, 5.9% and 7.7%, respectively. NRM did not significantly differ among age groups (p = 0.60). Two-year progression-free survival (PFS) and overall survival (OS) were 48% and 58%, respectively. PFS and OS were significantly longer in patients aged 60-64, however, survival rate was acceptable even in those aged 70 or over with a two-year OS of 46%. ASCT is feasible in selected elderly patients and age alone would not be a contraindication for ASCT. Eligibility should be individualized and identification of a subset of elderly patients at high risk of treatment-related morbidity or mortality warrants investigation.
    Full-text · Article · Jan 2014 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation

  • No preview · Article · Nov 2013 · Annals of Oncology
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    ABSTRACT: The gastrointestinal (GI) tract is one of the most common extranasal sites in extranodal NK/T-cell lymphoma (ENKTL). However, data regarding ENKTL involving the GI tract are relatively scarce. Thus, we performed a multicenter, multinational retrospective study to analyze clinical features and treatment outcomes of ENKTL involving the GI tract.Patients and methods: Patients with ENKTL involving the GI tract diagnosed in twelve participating centers between 1991 and 2012 were retrospectively analyzed from five Asian countries. The analysis of 81 patients with ENKTL involving the GI tract revealed that more than 60% of patients presented as advanced disease with B symptoms. 55 patients (68%) had GI manifestations including abdominal pain (n = 26, 32%), GI tract bleeding (n = 17, 21%) and bowel perforation (n = 12, 15%). The most common GI site was the small intestine, including the jejunum and ileum (n = 57, 70.3%). There were 34 patients (42%) who received systemic chemotherapy while 33 patients (41%) underwent surgery plus chemotherapy. However, 35 patients (43%) died due to disease progression, and treatment-related mortality including sepsis occurred in 17 patients (21%). Thus, the median overall survival was 7.8 months (95% Confidence interval: 3.9 -- 11.7 months). Patients who could undergo surgery plus chemotherapy showed a trend of better survival than those treated with chemotherapy alone. Overall, the data indicated that ENKTL involving the GI tract has a dismal prognosis despite active treatment including chemotherapy and surgery. Thus, more effective treatment strategies are required for this disease entity.
    Full-text · Article · Nov 2013 · Journal of Hematology & Oncology
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    ABSTRACT: Background Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive and associated with poor prognosis. Basic research to develop new treatment regimens is critically needed. Methods The effects of imatinib mesylate on MPNSTs were examined in six human MPNST cell lines and in a xenograft mouse model. Results The results showed expression of platelet-derived growth factor receptor-β and suppression of its phosphorylation by imatinib mesylate in all six cell lines. Imatinib mesylate effectively suppressed MPNST cell growth in vitro at concentrations similar to those used clinically (1.46 − 4.6 μM) in three of six cell lines. Knockdown of PDGFR-β by transfection with a specific siRNA also caused significant reduction in cell proliferation in the sensitive cell lines, but not in the resistant cell lines. Furthermore, imatinib mesylate also significantly suppressed colony formation within soft agar and tumor growth in xenograft models using two of the three sensitive MPNST cell lines. There was excellent agreement between in vitro and in vivo sensitivity to imatinib mesylate, suggesting possible selection of imatinib-sensitive tumors by in vitro analysis. Conclusions The results suggest that imatinib mesylate may be useful in the treatment of MPNST patients and in vitro studies may help select cells that are sensitive to imatinib mesylate in vivo.
    Full-text · Article · May 2013 · BMC Cancer

Publication Stats

6k Citations
878.15 Total Impact Points

Institutions

  • 2011-2016
    • Shimane University
      • • Department of Medicine
      • • Faculty of Medicine
      • • Department of Internal Medicine
      Matsu, Shimane, Japan
  • 2011-2015
    • The University of Shimane
      Хамада, Shimane, Japan
  • 1992-2012
    • Fukuoka University
      • • Department of Internal Medicine
      • • Faculty of Medicine
      • • Department of Pathology
      Hukuoka, Fukuoka, Japan
  • 2003-2006
    • St.Mary's Hospital (Fukuoka - Japan)
      Hukuoka, Fukuoka, Japan
  • 2002
    • Aichi Cancer Center
      Nagoya, Aichi, Japan
  • 1999
    • Kyushu Medical Center
      Hukuoka, Fukuoka, Japan