Nobuhiko Nakamura's research while affiliated with Gifu University Hospital and other places

Publications (70)

Article
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This phase II clinical trial aimed to evaluate the efficacy and safety of the combination therapy of bendamustine, cytarabine, and rituximab (BRAC) in patients with relapsed or refractory follicular lymphoma (FL) or mantle cell lymphoma (MCL). Thirteen patients were enrolled and received a median of 4 cycles (range 2–6) of BRAC. The complete respon...
Article
The BLd regimen, which is a triplet regimen of bortezomib (Bor), lenalidomide (Len), and dexamethasone (Dex), is effective against newly diagnosed multiple myeloma (NDMM). However, non-hematological toxicities, such as peripheral neuropathy (PN), often hamper long-term continuation of the regimen, particularly in older adult patients. In this study...
Article
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The controlling nutritional status (CONUT) score is a simplified nutritional index calculated from serum albumin, total cholesterol, and total lymphocyte count. This study evaluated the prognostic impact of the CONUT score on overall survival (OS) in patients with peripheral T-cell lymphoma (PTCL). A multicenter, retrospective cohort study includin...
Article
Oxidative stress serves an important role in carcinogenesis. The present study investigated the clinical significance of oxidative stress as a prognostic factor for diffuse large B-cell lymphoma (DLBCL). The participants comprised 55 consecutive patients with DLBCL. A commercially available derivatives of reactive oxygen metabolites (d-ROMs) test k...
Article
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Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from...
Preprint
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Azacitidine is a mainstay of therapy for high-risk MDS and other myeloid neoplasms. A significant correlation between azacitidine response and clinical outcome suggests a potential role of mutational profiling based on next-generation sequencing (NGS) before and after therapy in evaluating response and predicting overall survival (OS), which howeve...
Article
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Background The International Myeloma Working Group response criteria require two consecutive assessments of paraprotein levels. We conducted an exploratory analysis to evaluate whether a single response assessment could be a substitute for the International Myeloma Working Group criteria using data from JCOG1105, a randomized phase II study on melp...
Preprint
Full-text available
The controlling nutritional status (CONUT) is a simplified nutritional index calculated from serum albumin, total cholesterol, and the total lymphocyte count. Although the CONUT score is an independent prognostic factor in several hematological malignancies, the prognostic impact of the CONUT score in peripheral T-cell lymphoma (PTCL) is unclear. T...
Article
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Tryptophan (TRP) metabolism via the indoleamine 2,3-dioxygenase (IDO) subset of the kynurenine (KYN) pathway is one of the most important mechanisms of immune escape in cancer. TRP is converted into several biologically active KYN metabolites. However, the role of KYN metabolic products and related enzymes has not been clarified in patients with he...
Article
What is Known and Objective Our previous report indicated that teicoplanin (TEIC) caused fewer adverse effects than vancomycin (VCM) in patients with febrile neutropenia (FN) receiving haematopoietic stem cell transplantation (HSCT). However, we observed breakthrough methicillin‐resistant‐Staphylococcus haemolyticus (MR‐S haemolyticus ) infection d...
Article
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Recently, treatments for chronic hepatitis C virus (HCV) infection have significantly improved by the develop‑ment of direct‑acting antiviral agents (DAAs) and almost all patients with HCV can complete antiviral treatment without apparent adverse events. Malignant lymphoma, particularly B‑cell non‑Hodgkin's lymphoma, is one of the extrahepatic mani...
Article
A 72-year-old man developed dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid (BP) during treatment for type 2 diabetes mellitus and was administered prednisolone (PSL, 0.5 mg/kg). Despite PSL treatment at a daily dose of 19 mg/day, purpura appeared on his bilateral forearms 3 months later. He was diagnosed with acquired hemophilia A (...
Article
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Sarcopenia is a poor prognosis factor in some cancer patients, but little is known about the mechanisms by which malignant tumors cause skeletal muscle atrophy. Tryptophan metabolism mediated by indoleamine 2,3-dioxygenase is one of the most important amino acid changes associated with cancer progression. Herein, we demonstrate the relationship bet...
Article
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Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a diagnosis of exclusion, being the most common entity in mature T-cell neoplasms, and its molecular pathogenesis remains significantly understudied. Here, combining whole-exome and targeted-capture sequencing, gene-expression profiling, and immunohistochemical analysis of tumor sam...
Article
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Skeletal muscle atrophy and loss of adipose tissue, referred to as sarcopenia and adipopenia, respectively, are often observed in cancer patients. We investigated the impact of sarcopenia and adipopenia on clinical outcomes in 90 adult patients with newly diagnosed acute myeloid leukemia (AML) who received induction chemotherapy. Computed tomograph...
Article
A 30-year-old woman who was 14 weeks pregnant was admitted to our hospital due to purpura, nasal bleeding, and abdominal pain. She was diagnosed with acquired thrombotic thrombocytopenic purpura (TTP) based on the presence of hemolytic anemia, thrombocytopenia, decreased ADAMTS 13 activity (<0.01 IU/ml), and high ADAMTS 13 inhibitor levels (4.8 BU/...
Article
[Backgrounds] The controlling nutritional status (CONUT), one of the useful parameter of nutritional assessment tools, is a significant prognostic factor for various solid tumors. The CONUT score is an index calculated from the following factors; the serum albumin concentration (Alb), the total peripheral lymphocyte counts (Lymph) and total cholest...
Article
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We herein report a case of long-lasting pure red cell aplasia (PRCA) after major ABO-incompatible allogeneic stem cell transplantation (SCT) for acute lymphoblastic leukemia. The patient needed red blood cell (RBC) transfusion every week after SCT. On day 236, he was diagnosed with odontogenic infection, and the serum levels of IL-6 were elevated t...
Article
Pirarubicin (tetrahydropyranyl adriamycin [THP]) is an anthracyclin with less cardiotoxicity than doxorubicin (DOX). We previously reported the efficacy and safety of R‐THP‐COP consisting of rituximab (R), THP, cyclophosphamide (CPA), vincristine (VCR), and prednisolone (PSL) for diffuse large B cell lymphoma (DLBCL) in phase 2 studies. Here, we pr...
Article
Background: GP88 (progranulin; PGRN) is a secreted 88kDa glycosylated protein, with important functions, including inflammation and tumorigenesis. We assessed the significance of GP88 expression in survival outcomes of patients with malignant lymphoma (ML). Methods: Serum samples from 254 previously untreated ML patients were examined to measure...
Article
Management of constipation in patients receiving cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or CHOP-like chemotherapy regimens is important for prevention of paralytic ileus. We reported earlier that the laxative action of magnesium oxide is reversed by the concomitant use of antacids in cancer patients receiving opioid anal...
Article
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Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study i...
Article
Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma and the most common lymphoid neoplasm in adults. In the pre rituximab era, the standard therapy for patients with limited stage DLBCL had been three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) followed by involved-field radiot...
Article
Introduction:Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor well known to generate biological responses to dioxins. A recent study indicated that kynurenine was an endogenous ligand of AhR and was associated with suppression of the antitumor response. The essential amino acid tryptophan metabolism proceeds via the enzyme...
Chapter
Liver involvement is often observed in several hematologic diseases, as shown by abnormal liver function tests, abnormalities in liver imaging studies, or clinical symptoms presenting with hepatic manifestations. In hematologic malignancies, malignant cells often infiltrate into the liver and produce abnormal liver function test results accompanied...
Article
Indoleamine 2,3-dioxygenase exerts intense immunomodulatory effects due to enzymatic activities that catalyze the breakdown of the essential amino acid l-tryptophan. The activity of indoleamine 2,3-dioxygenase can be estimated by measuring serum l-kynurenine concentrations. Here, we aimed to determine the role of l-kynurenine as a prognostic factor...
Article
We analyzed 11 patients with multiple myeloma (MM) treated using denosumab in our institute. The median age was 69 years (range, 54-76 years), and 7 patients were male. Seven patients had presented with newly diagnosed MM. Four patients were initially treated with zoledronic acid, which was then later switched to denosumab. The median number of inj...
Article
We have reported the efficacy of the salvage chemotherapy P-IMVP16/CBDCA for patients with diffuse large B cell lymphoma (DLBCL) who had previously received CHOP before the availability of rituximab (R). Here, we confirmed the efficacy of R combined with P-IMVP16/CBDCA as a salvage chemotherapy for patients with DLBCL, who had previously received R...
Article
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Indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing intracellular enzyme of the L-kynurenine pathway, causes preneoplastic cells and tumor cells to escape the immune system by inducing immune tolerance; this mechanism might be associated with the development and progression of human malignancies. In the present study, we investigated the r...
Article
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Background: Febrile neutropenia is one of the most serious adverse events in patients with hematological malignancies and chemotherapy. The routine use of fluoroquinolone prophylaxis in patients with hematological malignancies is controversial. Therefore, we prospectively evaluated the efficacy and safety of prophylactic use of garenoxacin for febr...
Article
BACKGROUND: Bowel perforation after chemotherapy is a serious life-threatening complication of diffuse large B cell lymphoma (DLBCL) involving gastrointestinal tract. R Vaidya et al reported that 9 % of patients with gastrointestinal lymphoma developed a perforation, of which 55% occurred after chemotherapy, and DLBCL was the most common lymphoma a...
Article
Introduction: The intracellular enzyme indoleamine 2,3-dioxygenase (IDO) catalyzes the initial and rate-limiting step in the metabolism of the essential amino acid tryptophan along the L-kynurenine (KYN) pathway. Some metabolites derived from tryptophan via IDO catalysis such as KYN block antigen-driven specific T-cell proliferation and induce T-ce...
Article
Whilst maintenance therapy with rituximab has been established its role as for follicular lymphoma with high tumor burden, its clinical relevance in aggressive lymphoma still remains to be elucidated due to controversial results of previous studies. In order to address this issue, we conducted a meta-analysis targeting CD20 positive diffuse large B...
Article
Background: The response to treatment and overall survival of patients with acute myeloid leukemia (AML) are heterogeneous. A number of prognostic factors related to patient and tumor characteristics have been described for AML, including age, performance status, and karyotype. The depletion of skeletal muscle (sarcopenia) and adipose tissue (adipo...
Article
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Sarcopenia reportedly predicts poor outcomes in elderly patients with diffuse large B-cell lymphoma (DLBCL). However, because previous studies only involved elderly patients, it is difficult to generalize these results to all patients with DLBCL. We retrospectively analyzed 207 patients with DLBCL who received the R-CHOP or R-THP-COP regimen betwee...
Article
The CHOP regimen consisting of cyclophosphamide, doxorubicin (DOX), vincristine and prednisolone has been the most used regimen for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Pirarubicin [tetrahydropyranyladriamycin (THP)], a derivative of DOX, is an anthracycline with reportedly less cardiotoxicity than DOX. Here, we confirmed...
Article
Aim: A syngeneic color-coded imageable lymphoma model has been developed to visualize recruitment of host stromal cells by malignant lymphoma during metastasis. The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. Materials and methods: EL4 lymphoma cells expressing red fluoresc...
Article
Nonalcoholic steatohepatitis (NASH) has gained attention as a hepatic manifestation associated with metabolic syndrome and one of the causes for chronic liver damage leading to hepatocellular carcinoma. Although no standard medicinal treatment for NASH has been established, pentoxifylline (PTX), a medicine used to improve circulation, has recently...
Article
Full-text available
Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step in the metabolism of tryptophan along the kynurenine pathway. In tumors, increased IDO activity inhibits proliferation and induces apoptosis of T cells and natural killer cells. We investigated the therapeutic potential of IDO inhibitor 1-methyl-D-tryptophan (D-1MT) with cyclophosph...
Article
Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA We have developed a mouse model of highly malignant lymphoma. The EL4 cell line was established from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. Red fluorescent protein (RFP)-EL4 lymphoma cells were established. EL4-RFP cancer cells were...
Article
The immunomodulatory effects of indoleamine 2,3-dioxygenase (IDO) are ascribed to its ability to catalyze the breakdown of the L-tryptophan along the L-kynurenine pathway. Because blasts from patients with acute myeloid leukemia (AML) express IDO, the goal of this study was to investigate the role of L-kynurenine as a prognostic marker for AML. We...
Article
Full-text available
Concurrent seminoma and malignant lymphoma of the testis is rare. We present a case of concurrent seminoma and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in a 54-year-old man who complained of painless left testicular enlargement. Radical left orchiectomy was performed. Macroscopically, the tumor (4.0 × 3.0 cm) was creamy, soft,...
Article
BACKGROUND: The optimal management of relapsed or refractory aggressive B-cell lymphoma is not standardized. We previously reported the salvage chemotherapy with P-IMVP-16/CBDCA consisting of methylprednisolone (mPSL), carboplatin (CBDCA), etoposide (VP-16), ifosfamide (IFM), and methotrexate (MTX) for patients (pts) with aggressive non-Hodgkin's l...
Article
BACKGROUND: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is relatively rare, accounting for only 10% to 15% of non–Hodgkin's lymphomas, and is characterized by disseminated disease, with systemic symptoms, bone marrow involvement, and extranodal disease. There is no general consensus regarding the preferred induction chemotherapy...
Article
We have previously reported that polaprezinc in sodium alginate suspension (P-AG) inhibited the incidence of oral mucositis induced by radiochemotherapy in patients with head and neck cancer. The present study was designed to investigate whether P-AG prevents oral mucositis in all patients (36 patients) with hematological malignancy receiving high-...
Article
Background: Bendamustine (Ben) and combinations of Ben/rituximab(R) therapies have shown high efficacy in relapsed/refractory indolent B-cell non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL). No data exist about Ben retreatment after relapse, concerning efficacy and toxicity in these patients (pts) population. Patients and methods: Six pts...
Conference Paper
Background: We previously reported the efficacy of salvage chemotherapy with P-IMVP-16/CBDCA consisting of methylprednisolone (mPSL), carboplatin (CBDCA), etoposide (VP-16), ifosfamide (IFM), and methotrexate (MTX) for patients with aggressive non-Hodgkin's lymphoma who had previously received CHOP (Eur J Haematol 2002). The purpose of this study w...
Conference Paper
Background: Indoleamine 2,3-dioxygenase (IDO) is one of the main facrors which contribute to tumor-induced immunosuppressive mechanisms. IDO catalyzes the essential amino acid L-tryptophan to L-kynurenine (L-kyn). The activity of IDO can be estimated by measuring the serum concentration of L-kyn. We have previously reported the utility of L-kyn as...
Article
Abstract The immunomodulatory effects of indoleamine 2,3-dioxygenase (IDO) are ascribed to its ability to catalyze breakdown of the essential amino acid L-tryptophan. We applied reverse transcription PCR (RT-PCR) to examine IDO mRNA expression in AML blasts, and investigated its clinical significance. We enrolled 62 patients with AML between April...
Article
Background Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step in the catabolism of tryptophan along the kynurenine pathway. In tumors, increased IDO activity inhibits T cell and natural killer cell proliferation and induces apoptosis. We have previously reported that IDO expression in lymphoma cells and serum concentration of kynure...
Article
Abstract Lenalidomide is one of the most potent immunomodulatory drugs and exerts anti-tumor effects on multiple myeloma (MM). Lenalidomide stimulates T and NK cells to produce Th1-type cytokines, while it inhibits the production of Th2-type cytokines and pro-inflammatory cytokines in vitro. A 76-year-old man with MM had been on several courses of...
Article
Full-text available
Hepatic immune regulation is associated with the progression from simple steatosis to non-alcoholic steatohepatitis, a severe condition of inflamed fatty liver. Indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme that mediates the catabolism of L-tryptophan to L-kynurenine, plays an important role in hepatic immune regulation. In the present...
Article
Background Serum soluble tumor necrosis factor receptor 2 (sTNFR2) concentration predicted the clinical outcome of patients with aggressive non-Hodgkin's lymphoma including diffuse large B-cell lymphoma (DLBCL) treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) in our previous study. However, after rituximab (R) was in...
Article
1555 Background Tumor-infiltrating immune cells perform important functions in host immune reaction against tumor cells including diffuse large B cell lymphoma (DLBCL). Recently, variable tumor-infiltrating cells were reported to give a influence for prognosis, for example, regulatory T cell (T reg), cytotoxic T cell, macrophage and mast cell etc....
Article
5107 Background Over the past few decades, investigators have worked to identify prognostic factors in non-Hodgkin lymphoma (NHL) so an appropriate therapeutic plan can be put in action. In addition to conventional prognostic factors such as the international prognostic index (IPI), many biomarkers including cytokines, chemokines, enzymes, or gene...
Article
We describe two patients with T cell prolymphocytic leukemia (T-PLL) who exhibited the same complex karyotype, including an additional segment at 1p36.1. One presented with secondary progression following an initial stable clinical course, and the other with typically progressive disease. Features of the cerebriform variant were identified in the p...
Article
1594 Background Tumor-infiltrating immune cells perform important functions in host immune reaction against tumor cells including diffuse large B cell lymphoma (DLBCL). Recently, variable tumor-infiltrating cells were reported to give a influence for prognosis, for example, regulatory T cell (T reg), cytotoxic T cell, macrophage and mast cell etc....
Article
1575 Background We have previously reported that serum concentration of serum-soluble tumor necrosis factor receptor 2 (sTNF-R2) predicts the clinical outcome of patients with aggressive non-Hodgkin's lymphoma (NHL) treated with CHOP without rituximab (Goto et al. 2005). We extracted the diffuse large B-cell lymphoma (DLBCL) patients from aggressi...
Article
2639 INTRODUCTION Recent studies have suggested that one mechanism of immune escape could be catabolism of the essential amino acid tryptophan, via indoleamine 2,3-dioxygenase (IDO) along the kynurenine pathway. Some metabolites derived from tryptophan by IDO, such as L-kynurenine, block antigen-driven specific T-cell proliferation and induce T-ce...
Article
4379 Background Indoleamine 2,3-dioxygenase (IDO) is endowed with intense immunomodulatory effects due to its enzymatic activities that catalyse the breakdown of the essential amino acid L-tryptophan. Recently, blasts of patients with acute myeloid leukemia were shown to express IDO. We determined IDO mRNA expression in leukemic blasts of patients...

Citations

... Though IPI and the Prognostic Index for PTCL-U (PIT) are widely applied in prognostic risk stratification, they lack nutritional index. Nakamura et al. [52] enrolled 99 cases and analyzed their CONUT score at diagnosis. Based on their survival status, those PTCL patients were divided into non-survivor group (n = 55) and survivor group (n = 44). ...
... The presence of these mutations at diagnosis is associated with high risk of disease progression in CML. A recent comprehensive genetic analysis demonstrated that, compared with clinical parameters, specific genetic lesions are better predictors of survival in CML-BP [37,38]. Only a small case series on somatic mutations in childhood CML-CP has been published, in which only ASXL1 mutations were identified in 6 of 21 patients with CML [39]. ...
... The presence of mecA and vanB carrying bacteria is indicative of possible horizontal transmission of resistant bacteria from humans to animals, since, methicillin and vancomycin are not used in the treatment of animal infection. Another worrying fact is the occurrence of both mecA and vanB genes in the same study since vancomycin is considered the first choice of antibiotics used in treatment against methicillinresistant Staphylococcus (MRS) [16,[60][61][62][63][64][65][66]. ...
... It may be just an association or DAAs might have some relation to this. Many studies shows large number of patients who developed 4541 hepatocellular carcinoma (HCC) post DAAs treatment, only case reports described nine patients who developed lymphoid malignancies post DAAs since 2016 until now, other studies shows that DAAs might have an effect on cell-mediated immunity (11)(12)(13)(14)(15)(16)(17) . ...
... Emerging evidence showed that its deficiency plays a key role in the development of anxiety, depression, fatigue, muscle weakness, sleep, and mood disturbances. Moreover, Ninomiya et al. revealed that low levels of tryptophan underlie the pathogenesis of muscle atrophy [57]. Furthermore, this propensity may imply that Try depletion causes weakening of the diaphragm muscle and, therefore, dyspnea. ...
... One study showed the use of the IDO inhibitor, 1-methyl tryptophan (1MT) with adriamycin in AML caused significant inhibition of blast cell proliferation and a significant increase in lymphocyte counts when used alone (266). Nakamura et al. also showed that a combination of 1MT and cyclophosphamide is an effective treatment for IDO-positive lymphoma in a model mouse by reducing Tregs and breaking tumor tolerance (267). However, failure of phase III clinical trial (ECHO-301/KN-252) where Epacadostat an IDO inhibitor in combination with anti-PD-1 antibody pembrolizumab was used in metastatic melanoma patients did not demonstrate improved progression-free survival and OS and thus terminated early (268,269) have pushed for a re-think on the clinical benefits of IDO inhibitors in cancer. ...
... However, nearly half of the patients become refractory to the R-CHOP regimen [12][13][14]. Early identification of drug resistance and therapeutic failures are crucial for the identification of high-risk patients [15][16][17][18]. Accumulating studies have investigated the molecular mechanisms underlying resistance to the R-CHOP regimen in DLBCL, which is key to improving the treatment response [19,20]. ...
... In cases of DLBCL, perforation can affect other hollow organs including the gastrointestinal tract and trachea [37][38][39] . Although chemotherapy dose reduction/delay followed by the standard full-dose regimen has been used in an attempt to minimize perforation in non-cardiac cases [37] , concerns arise as strategy may also decrease treatment intensity leading to reduced therapeutic effects and suboptimal outcomes [40] . ...
... Increased expression of IDO in cancer correlates with poor disease outcome and reduced function of T cells, which can be rescued by pharmacologically blocking IDO with 1-methyltryptophan (Platten et al., 2012;Uyttenhove et al., 2003). Other immunosuppressive effects mediated by IDO as well as the alternative enzyme tryptophan-2,3-dioxygenase 2 (TDO2) include tryptophan catabolites, which activate aryl hydrocarbon receptor and apoptosis in select T cell subsets (Fallarino et al., 2002;Ninomiya et al., 2016;Platten et al., 2012). ...
... Thereby, CD45 can act as a tumor suppressor by directly dephosphorylating the JAK tyrosine kinases in response to cytokine signaling. To support a role as a tumor suppressor for CD45, loss of function genetic alterations of PTPRC gene have been recently reported in peripheral T cell lymphoma, not otherwise specified (PTCL, NOS) (36). Because of the absence of the major substrate of CD45, LCK, it is plausible that in ALK+ ALCL the CD45 phosphatase activity affects the JAK/STAT pathway therefore playing a role as a tumor suppressor. ...