Junji Suzumiya

Shimane University, Matsu, Shimane, Japan

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Publications (224)812.89 Total impact

  • [Show abstract] [Hide abstract]
    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. However, our study could not explain how the sensitization to vincristine is related to the effects of cotylenin A on the 14-3-3 signaling pathway and further studies will be needed.
    International Journal of Oncology 02/2015; DOI:10.3892/ijo.2015.2882 · 2.77 Impact Factor
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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.
    American Journal of Hematology 11/2014; DOI:10.1002/ajh.23897 · 3.48 Impact Factor
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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.
    British Journal of Haematology 10/2014; DOI:10.1111/bjh.13167 · 4.94 Impact Factor
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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(+) AML. 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 AML cell chemotaxis to the therapy-protective bone marrow niche, where CXCL12 is abundantly expressed.
    Journal of Biological Chemistry 09/2014; DOI:10.1074/jbc.M114.568287 · 4.60 Impact Factor
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    Dataset: 2403738a
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    Dataset: 2403738a
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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.
    Journal of Clinical Oncology 03/2014; 32(11). DOI:10.1200/JCO.2013.52.0924 · 17.88 Impact Factor
  • 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%.
    Nippon rinsho. Japanese journal of clinical medicine 03/2014; 72(3):493-8.
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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.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2014; DOI:10.1016/j.bbmt.2014.01.025 · 3.15 Impact Factor
  • Annals of Oncology 11/2013; 24(suppl 9):ix88-ix88. DOI:10.1093/annonc/mdt460.111 · 6.58 Impact Factor
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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.
    Journal of Hematology & Oncology 11/2013; 6(1):86. DOI:10.1186/1756-8722-6-86 · 4.93 Impact Factor
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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-beta 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 muM) in three of six cell lines. Knockdown of PDGFR-beta 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.
    BMC Cancer 05/2013; 13(1):224. DOI:10.1186/1471-2407-13-224 · 3.32 Impact Factor
  • Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 11/2012; DOI:10.1038/leu.2012.321 · 10.16 Impact Factor
  • Journal of Clinical Oncology 09/2012; 30(28):3561-3561. DOI:10.1200/JCO.2012.45.0288 · 17.88 Impact Factor
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    ABSTRACT: Reports of non-anaplastic peripheral T-cell lymphoma (PTCL) in paediatric patients, especially results of stem cell transplantation (SCT), are relatively rare. We herein report the results of SCT using the Transplant Registry Unified Management Program system of the Japanese Society of Stem Cell Transplantation in paediatric patients with non-anaplastic PTCL. We analysed 26 patients (13 females and 13 males) aged ≤18 years with non-anaplastic PTCL who underwent a total of 28 SCT. Median age at transplantation was 13·5 years (range: 0-18 years). PTCL not otherwise specified was diagnosed in 17 patients; extranodal Natural Killer (NK)/T cell lymphoma, nasal type in nine; and subcutaneous panniculitis-like T-cell lymphoma in two. Transplantation was with syngeneic donor in one, related donor in 10; unrelated donor in 10; and auto transplantation in 7. Five-year overall survival rate and event-free survival rate was 62·96% and 55·56%, respectively. Male gender, chronic graft-versus-host disease (GVHD), and reduced intensity conditioning were good prognostic factors in all patients. In 20 patients with refractory or relapsed disease, male gender and chronic GVHD were also good prognostic factors. This study is the first report concerning transplantation in children with non-anaplastic PTCL, although the number of patients was small. Larger studies are needed to confirm these findings.
    British Journal of Haematology 08/2012; 159(1):88-93. DOI:10.1111/bjh.12001 · 4.94 Impact Factor
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    ABSTRACT: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is an Epstein-Barr virus (EBV)-associated lymphoma for which a new chemotherapeutic regimen called SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) recently showed promising results. The amount of EBV-DNA was prospectively measured in whole-blood and plasma samples by real-time quantitative PCR from 26 patients registered in the SMILE phase II study. Before treatment, the EBV-DNA was detected in 22 samples of whole blood with a median number of 3,691 copies/mL (range: 0-1.14 × 10(7)), but 15 samples of plasma with a median of 867 copies/mL (range: 0-1.27 × 10(7)). Results of these 2 measurements of EBV-DNA well correlated (R(2) = 0.994, P < 0.001). The overall response rate to SMILE was significantly higher in patients with less than 10(5) copies/mL of EBV-DNA in whole blood at enrollment (90% vs. 20%, P = 0.007) and in patients with less than 10(4) copies/mL of EBV-DNA in plasma (95% vs. 29%, P = 0.002). The incidence of grade 4 toxicity of SMILE other than leukopenia/neutropenia was significantly higher in patients with 10(5) copies/mL of EBV-DNA or more in whole blood (100% vs. 29%, P = 0.007) than that of others and in patients with 10(4) copies/mL or more in plasma (86% vs. 26%, P = 0.002). These findings suggest that whole blood is more sensitive for clinical use than plasma. The EBV-DNA amount in whole blood was useful for predicting tumor response, toxicity, and prognosis after SMILE chemotherapy for ENKL.
    Clinical Cancer Research 06/2012; 18(15):4183-90. DOI:10.1158/1078-0432.CCR-12-1064 · 8.19 Impact Factor
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    ABSTRACT: Background Clinical features and outcomes of extranodal natural killer/T-cell lymphoma (ENKL) arising from extranasal sites are not fully understood. The purpose of this study was to study the prognosis and treatment outcome of skin/soft tissue primary ENKL. Patients and methods This multicenter retrospective study included 48 patients with skin/soft tissue primary ENKL diagnosed from 1993 to 2010. Results Patients with Ann Arbor stage I, T1-2N0M0 by International Society for Cutaneous Lymphomas-European Organization of Research and Treatment of Cancer TNM (tumour-node-metastasis) stage, International prognostic index score of 0-1, and a Korean prognostic index (KPI) score of 0-1 were associated with better survival. Four of five patients with T1-2N0M0 disease achieved complete response with radiation alone. In disseminated disease, only 6 of 13 patients responded to anthracycline-containing chemotherapy, and all the two patients receiving SMILE showed response. Conclusion In conclusion, we identified the prognostic value of KPI, and we suggest a treatment recommendation according to the TNM (tumour-node-metastasis) stage. Radiotherapy with/without chemotherapy seemed to be optimal in localized disease. In advanced stages, a more aggressive treatment regimen with newer agents should be sought.
    Annals of Oncology 04/2012; 23(10):2703-7. DOI:10.1093/annonc/mds096 · 6.58 Impact Factor
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    ABSTRACT: The prognosis of acute- and lymphoma-type adult T-cell leukemia/lymphoma (ATL) is poor, but there is marked diversity in survival outcomes. The aim of this study was to develop a prognostic index (PI) for acute- and lymphoma-type ATL (ATL-PI). In a retrospective review, data from 807 patients newly diagnosed with acute- and lymphoma-type ATL between January 2000 and May 2009 were evaluated. We randomly divided subjects into training (n = 404) and validation (n = 403) samples, and developed a PI using a multivariable fractional polynomial model. Median overall survival time (MST) for the 807 patients was 7.7 months. The Ann Arbor stage (I and II v III and IV), performance status (0 to 1 v 2 to 4), and three continuous variables (age, serum albumin, and soluble interleukin-2 receptor [sIL-2R]) were identified as independent prognostic factors in the training sample. Using these variables, a prognostic model was devised to identify different levels of risk. In the validation sample, MSTs were 3.6, 7.3, and 16.2 months for patients at high, intermediate, and low risk, respectively (P < .001; χ(2) = 89.7, 2 df; log-rank test). We also simplified the original ATL-PI according to dichotomizing age at 70 years, serum albumin at 3.5 g/dL, and sIL-2R at 20,000 U/mL and developed an easily calculable PI with prognostic discrimination power (P < .001; χ(2) = 74.2, 2 df; log-rank test). The ATL-PI is a promising new tool for identifying patients with acute- and lymphoma-type ATL at different risks.
    Journal of Clinical Oncology 04/2012; 30(14):1635-40. DOI:10.1200/JCO.2011.38.2101 · 17.88 Impact Factor
  • Junji Suzumiya, Masaya Inoue, Satoshi Kumanomido
    Nippon rinsho. Japanese journal of clinical medicine 04/2012; 70 Suppl 2:470-5.
  • Junji Suzumiya, Ichiro Moriyama, Koshi Kawakami
    Nippon rinsho. Japanese journal of clinical medicine 04/2012; 70 Suppl 2:519-24.

Publication Stats

5k Citations
812.89 Total Impact Points

Institutions

  • 2011–2015
    • Shimane University
      • Department of Internal Medicine
      Matsu, Shimane, Japan
  • 1992–2012
    • Fukuoka University
      • • Department of Internal Medicine
      • • Faculty of Medicine
      • • Department of Pathology
      Hukuoka, Fukuoka, Japan
  • 2010
    • The University of Shimane
      Хамада, Shimane, Japan
  • 2003–2009
    • St.Mary's Hospital (Fukuoka - Japan)
      Hukuoka, Fukuoka, Japan
    • Aichi Cancer Center
      Ōsaka, Ōsaka, Japan
  • 2007
    • Kurume University
      Куруме, Fukuoka, Japan
    • Fujita Health University
      Nagoya, Aichi, Japan
    • Fourth Military Medical University
      • State Key Laboratory of Cancer Biology
      Xi’an, Liaoning, China
  • 2004
    • Nagasaki University
      Nagasaki, Nagasaki, Japan
  • 2002
    • Akita University
      Akita, Akita, Japan
  • 1999
    • Kyushu Medical Center
      Hukuoka, Fukuoka, Japan