Details of a Researcher - IYAMA Satoshi

Papers - IYAMA Satoshi

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A case of ulcerative colitis accompanied with myelodysplastic syndrome successfully treated by cyclosporine

Sho Takahashi, Yasushi Sato, Tamotsu Sagawa, Shingo Tanaka, Kazuyuki Murase, Kohichi Takada, Satoshi Iyama, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Ganji Kuroiwa, Michiaki Hirayama, Tetsuro Okamoto, Junji Kato

Journal of Japanese Society of Gastroenterology ( 8 ) 108 ( 8 ) 1405 - 1412 2011.08 [Refereed]

A 64-year-old man had been admitted to a previous hospital because of melena and a diagnosis of ulcerative colitis (UC, pancolitis type) had been made. He had received prednisolone and 5-ASA but steroid-induced hyperamylasemia had developed. Prednisolone had been tapered and halted, but it had resulted in UC relapse and thrombocytopenia. Then, he was referred to our hospital due to severe melena with hypovolemic shock. However, he was also positive for CMV antigen. Thus, we attempted to treat him with ganciclovir for CMV and intravenous cyclosporine (CsA) for UC. According to his clinical course, a reduction of CsA blood concentration induced leukocytopenia. Myelodysplastic syndrome (MDS, RAEB-1) was then revealed after bone marrow biopsy. A high blood CsA concentration may cause the improvement of UC and MDS conditions.

DOI PubMed

Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory iron deficiency anemia

Tsutomu Sato, Satoshi Iyama, Kazuyuki Murase, Yusuke Kamihara, Kaoru Ono, Shohei Kikuchi, Kohichi Takada, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Junji Kato

INTERNATIONAL JOURNAL OF HEMATOLOGY ( SPRINGER TOKYO ) 94 ( 1 ) 101 - 103 2011.07 [Refereed]

Iron-refractory iron deficiency anemia (IRIDA) is a rare autosomal-recessive disorder hallmarked by hypochromic microcytic anemia, low transferrin saturation, and unresponsiveness to oral iron with partial recovery after parenteral iron administration. The disease is caused by mutations in TMPRSS6 (transmembrane protease serine 6) that prevent inactivation of membrane-bound hemojuvelin, an activator of hepcidin transcription. To date, 38 cases have been characterized and reported in European countries and the United States. In this paper, we describe the first case of a Japanese female with IRIDA, who carried a novel mutation (K253E) in the CUB (complement factor C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain of the TMPRSS6 gene.

DOI PubMed

Iron chelator deferasirox rescued mice from Fas-induced fulminant hepatitis

Tsutomu Sato, Masayoshi Kobune, Kazuyuki Murase, Yukari Kado, Tetsuro Okamoto, Shingo Tanaka, Shohei Kikuchi, Hiroyuki Nagashima, Yutaka Kawano, Kohichi Takada, Satoshi Iyama, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Junji Kato

HEPATOLOGY RESEARCH ( WILEY-BLACKWELL ) 41 ( 7 ) 660 - 667 2011.07 [Refereed]

Aim: Fulminant hepatitis is a disease characterized by development of hepatic failure due to severe liver cell injury. Orthotopic liver transplantation is the therapy proven to improve patient survival; however, less burdensome and safer strategies are required. In a previous study, we showed that iron was intimately involved in hepatocyte apoptosis by demonstrating that spontaneous development of fulminant hepatitis in Long-Evans cinnamon rats was prevented by feeding an iron-deficient diet. Recently, a new iron chelator, deferasirox, has become widely available for the treatment of transfusional hemosiderosis. Deferasirox demonstrated good efficacy and improved compliance due to convenient, once-daily p.o. administration. Our aim was to investigate the efficacy of deferasirox as a therapeutic drug against fulminant hepatitis. Methods: Human primary hepatocytes undergoing Fas-stimulated apoptosis were challenged with deferoxamine (DFO) in vitro. In further in vivo experiments, we tested DFO in a mice model of fulminant hepatitis induced by Fas-stimulation. Results: The apoptosis-inducing activity of anti-Fas antibody on human primary hepatocytes was inhibited by the chelation of iron with DFO. DFO suppressed the Fas-induced production of reactive oxygen species (ROS) and the activation of caspase-3, both of which were also suppressed by antioxidant, N-acetyl-L-cystein. In the in vivo experiments, deferasirox effectively reduced hepatic iron concentrations and rescued mice from Fas-induced fulminant hepatitis. Conclusion: These findings indicated that the iron chelation exerted a hepatoprotective effect by scavenging ROS upstream of caspase-3 and that iron chelation with deferasirox is a potential treatment for patients with fulminant hepatitis.

DOI PubMed

Establishment of a simple test for iron absorption from the gastrointestinal tract

Masayoshi Kobune, Koji Miyanishi, Kohichi Takada, Yutaka Kawano, Hiroyuki Nagashima, Shohei Kikuchi, Kazuyuki Murase, Satoshi Iyama, Tsutomu Sato, Yasushi Sato, Rishu Takimoto, Junji Kato

INTERNATIONAL JOURNAL OF HEMATOLOGY ( SPRINGER TOKYO ) 93 ( 6 ) 715 - 719 2011.06 [Refereed]

Recent studies on iron metabolism have begun to reveal the molecular mechanisms underlying iron absorption, which is dramatically affected in several disorders. In the clinical setting, the ability to determine the status of iron absorption would aid in the diagnosis of pathological conditions. Efforts to develop an oral iron absorption test (OIAT) date back to at least 60 years. However, previous procedures were associated with a number of problems, such as radiation exposure and low reproducibility. In an attempt to resolve these issues, we employed sodium ferrous citrate (SFC), by which the influence of various nutrients and drugs on iron absorption was markedly reduced. We found that OIAT using SFC was simple to perform in both hospitalized patients and outpatients. The increment of serum iron and % transferrin saturation at 120 min after SFC administration was useful in distinguishing iron absorption between healthy volunteers, patients with iron-deficiency anemia, and patients with anemia secondary to chronic disorders, which are respectively characterized by normal, enhanced, and reduced iron absorption. Thus, the SFC-based OIAT may represent a viable screening test for the evaluation of gastrointestinal iron absorption.

DOI PubMed

Tuberculous pleuritis with onset of refractory pleural effusion after chemoradiotherapy for esophageal cancer

Masahiro Hirakawa, Yasushi Sato, Hiroyuki Ohnuma, Tamotsu Sagawa, Hirotoshi Ishiwatari, Kazuyuki Murase, Satoshi Iyama, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Masayoshi Kobune, Rishu Takimoto, Junji Kato

Journal of Japanese Society of Gastroenterology ( 2 ) 108 ( 2 ) 231 - 237 2011.02 [Refereed]

A 75-year-old man received chemoradiotherapy (CRT) for stage IVa esophageal cancer and complete response (CR) was obtained. However, he was referred to our department for recurrence in an area of esophagus not included in the previously irradiated field. Left pleural effusion increased after admission. Tuberculous pleuritis was eventually diagnosed by thoracoscopic pleural biopsy. It is necessary to accurately diagnose the cause of pleural effusion after CRT, because treatment strategies greatly depend on it. It is also necessary to consider the possible onset of tuberculous pleuritis, in particular, in patients with a history of tuberculosis infection.

DOI PubMed

Immune thrombocytopenia associated with de novo hepatitis B in a follicular lymphoma patient after autologous peripheral blood stem cell transplantation

Hiroyuki Kuroda, Tamaki Sakurai, Michiko Yamada, Naoki Uemura, Michihiro Ono, Tomoyuki Abe, Shigeyuki Fujii, Masahiro Maeda, Kyuhei Kohda, Yasuo Hirayama, Yuko Fujimi, Satoshi Iyama, Junji Kato

Biotherapy 25 ( 1 ) 579 - 583 2011.01

We report a patient with immune thrombocytopenic purpura (ITP) associated with de novo hepatitis B after cessation of preemptive lamivudine therapy. A 52-year-old man was diagnosed with relapse follicular lymphoma (FL) he had received five courses of rituximab plus CHOP (R-CHOP) following an autologous peripheral blood stem cell transplantation (APBSCT) in January, 2008. As he was hepatitis B virus (HBV) surface antigen-positive, lamivudine was administered simultaneously with both R-CHOP and APBSCT to prevent a HBV reactivation. He developed de novo hepatitis due to HBV reactivation 2 months after cessation of lamivudine in June, 2009. He was admitted to a hospital, complaining of purpura and oral bleeding in July, 2009. Based on his elevated level of platelet-associated IgG (PAIgG), a diagnosis of ITP was made. After intravenous immunoglobulin injections and treatment with entecavir, thrombocytopenia and viral replication were controlled. In an APBSCT recipient whose idiotypic network is still forming, there is a higher likelihood of an expression of cross-reactive auto-antibodies after HBV reactivation.

Effective treatment by both anti-androgen therapy and chemotherapy for a patient with advanced salivary duct carcinoma

Hiroyuki Kuroda, Tamaki Sakurai, Michiko Yamada, Naoki Uemura, Michihiro Ono, Tomoyuki Abe, Shigeyuki Fujii, Masahiro Maeda, Kyuhei Kohda, Masahiko Obata, Masakatsu Ando, Satoshi Iyama, Junji Kato

Japanese Journal of Cancer and Chemotherapy ( Japanese Journal of Cancer and Chemotherapy Publishers Inc. ) 38 ( 4 ) 627 - 630 2011 [Refereed]

Salivary duct carcinoma (SDC) is a high-grade malignant tumor arising predominantly in the parotid gland. Androgen receptor (AR) expression was mainly restricted to SDC in salivary cancer. We report successful treatment of a patient with advanced SDC using an endocrine chemotherapy. A 76-year-old man was hospitalized with lumbalgia and swelling of left submandibular region. Radiological examination indicated a tumor in left submandibular gland and metastatic tumors in lumbar vertebra, accompanied by swollen lymph nodes of the neck, mediastinum. Needle biopsies of both vertebral tumor and cervical lymph node revealed SDC. Positive nuclear staining was observed against AR in tumor cells of our patient by immunohistochemical analysis. He obtained a partial response after 1 course of treatment with both anti-androgen therapy and palliative chemotherapy using paclitaxel. In contrast to previous reports of poor response to chemotherapy alone and short-term survival of patients with SDC, our patient has demonstrated that chemotherapy combined with anti-androgen therapy may be an effective modality as a therapeutic regimen for SDC.

PubMed

Successful rituximab treatment of methotrexate-associated B-cell lymphoproliferative disorder arising in two patients with latency type II epstein-barr viral infection

Hiroyuki Kuroda, Tamaki Sakurai, Michiko Yamada, Naoki Uemura, Michihiro Ono, Tomoyuki Abe, Shigeyuki Fujii, Masahiro Maeda, Nanase Ishida, Kyuhei Kohda, Masahiko Obata, Masakatsu Ando, Satoshi Iyama, Junji Kato

Biotherapy 24 ( 6 ) 507 - 511 2010.11

We have encountered two patients with methotrexate (MTX)-associated B-cell lymphoproliferative disorder (B-LPD) as a complication of rheumatoid arthritis (RA). Case 1 was a 68-year-old woman. She complained of right neck swelling during low-dose MTX treatment for RA. Her neck lymph node biopsy revealed polymorphic B-LPD. Case 2 was a 67-year-old man. He has hospitalized for right neck lymph node swelling and throat pain during low-dose MTX treatment for RA. Diffuse large B cell lymphoma was diagnosed by his tonsil biopsy. The immunohistochemical analyses of B-LPD in those patients showed latency type II Epstein-Barr virus (EBV) infection. MTX withdrawal and observation for a month revealed no spontaneous regression of B-LPD in both cases. Therefore, we administered rituximab once, it had been tumor remission of B-LPD in parallel with the EBV-DNA level in peripheral blood. Thus, their arthralgia was improved, and the MMP-3 level decreased. MTX withdrawal does not necessarily lead to spontaneous remission of tumors in B-LPD patients with latency type II EBV infection. Rituximab therapy proved effective for not only MTX-associated B-LPD but also RA in our patients.

ENDOSCOPIC FINDINGS OF ENTEROPATHY-TYPE T-CELL LYMPHOMA BY DOUBLE-BALLOON ENTEROSCOPY AND CAPSULE ENDOSCOPY

Yasushi Sato, Michihiro Ono, Tamotsu Sagawa, Rishu Takimoto, Masahiro Hirakawa, Hiroyuki Ohnuma, Tsutomu Sato, Satoshi Iyama, Kazuyuki Murase, Koji Miyanishi, Masayoshi Kobune, Junji Kato

DIGESTIVE ENDOSCOPY ( WILEY-BLACKWELL ) 22 ( 3 ) 243 - 245 2010.07 [Refereed]

DOI PubMed

[Evaluation of the efficacy of liposomal amphotericin B].

Iyama S, Murase K, Sato T, Kikuchi S, Sato Y, Kobune M, Takimoto R, Kato J

Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases ( 2 ) 84 ( 2 ) 182 - 186 2010.03 [Refereed]

A retrospective study was performed to evaluate the efficacy and safety of liposomal amphotericin B (L-AMB) in a total of 32 cases who were among patients hospitalized at the Fourth Department of Internal Medicine, Sapooro Medical University from December 2006 to April 2008. Primary diagnoses were hematologic diseases in 87.5％of subjects. The most common hematologic diseases included acute myelogenous leukemia in 50％of the subjects, followed by malignant lymphoma in 12.5％of the subjects. The mean administration period was 14.2±12.9 days, and the mean cumulative dose was 1,786±2,181 mg. L-AMB improved 21 of 29 cases (72.4％) with some fungal infections or fever-associated neutropenia. Adverse events occurred in 9 cases to a slight degree, in 7 cases to a moderate degree, and in no case to a severe degree. Hypokalemia and hypercreatininemia were seen in 7 cases (21.9％) and 4 cases (12.5％), respectively, but these adverse reactions were so mild that the treatment did not need to be discontinued. Any adverse reactions for which treatment administration was discontinued were confirmed to have disappeared at the end of the study. These results support the efficacy and safety of L-AMB in accordance with previous foreign reports. It was noteworthy that early use of L-AMB prior to established diagnosis sometimes better therapeutic outcomes. It was also suggested that L-AMB could be safely administered while controlling electrolyte balance, such as serum potassium concentration, with sufficient fluid replacement, including physiological saline infusion. There are limitations in the use of the conventional form of amphotericin B because of its renal toxicity and other reasons. However, L-AMB had fewer side effects, so the agent was considered useful for the treatment of hematologic disease patients who either had mycosis or carried a risk for fungal infection.

DOI PubMed CiNii

Pure Red Cell Aplasia Associated with Good's Syndrome Accompanied by Decreased Stem Cell Factor Production in the Bone Marrow

Kageaki Kuribayashi, Akihito Fujimi, Masayoshi Kobune, Rishu Takimoto, Shohei Kikuchi, Satoshi Iyama, Junji Kato, Yoshiro Niitsu, Naoki Watanabe

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE ) 49 ( 5 ) 377 - 382 2010 [Refereed]

DOI PubMed

Therapeutic results in patients with biphenotypic acute leukemia at Sapporo Medical University Hospital

Kazuyuki Murase, Satoshi Iyama, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Junji Kato

Japanese Journal of Cancer and Chemotherapy ( Japanese Journal of Cancer and Chemotherapy Publishers Inc. ) 37 ( 10 ) 2011 - 2013 2010 [Refereed]

We reviewed the results of 6 patients with biphenotypic acute leukemia (BAL) which the diagnostic standard of the European Group for the Immunological Characterization of Leukemia (EGIL) at Sapporo Medical University Hospital between 2006 and 2008. There were 5 males and 1 females with an average age of 35 years. Among them, 4 were B lymphoid and myeloid, 2 were T lymphoid and myeloid, and one was T/B lymphoid. Two of 4 patients did not attain complete remission, and two relapsed after first treatment with acute myeloblastic leukemia (AML) protocol. On the other hand, two showed complete remission after the acute lymphoblastic leukemia (ALL) protocol. One of 4 patients survived who had been treated with hematopoietic stem cell transplantation as a post-remission therapy. The ALL protocol was good for the induction therapy. However, overall treatment-related deaths were 4 patients and considerable caution was necessary.

PubMed

ヘッジホッグ・シグナル伝達阻害剤は、CD34+白血病細胞の薬剤耐性を解除する

菊地尚平, 小船雅義, 村瀬和幸, 井山諭, 佐藤勉, 瀧本理修, 河野豊, 宮西浩嗣, 佐藤康史, 加藤淳二

臨床血液 ( (一社)日本血液学会-東京事務局 ) 50 ( 9 ) 1113 - 1113 2009.09 [Refereed]

[Successful induction of complete remission by gemtuzumab ozogamicin following chemotherapy in three patients with relapsed or refractory acute myeloid leukemia].

Hirayama Y, Terui T, Koike K, Neda H, Ishitani K, Kohda K, Kuroda H, Iyama S, Sato T, Kobune M, Takimoto R, Kato J

[Rinsho ketsueki] The Japanese journal of clinical hematology ( 8 ) 50 ( 8 ) 663 - 665 2009.08 [Refereed]

DOI PubMed CiNii

シクロパミンは、CD34陽性白血病細胞の薬剤耐性を解除する(Cyclopamine dramatically restores drug resistance of CD34+ leukemic cells)

小船雅義, 井山諭, 佐藤勉, 瀧本理修, 菊地尚平, 村瀬和幸, 河野豊, 宮西浩嗣, 佐藤康史, 加藤淳二

日本癌学会総会記事 ( 日本癌学会 ) 68回 480 - 480 2009.08 [Refereed]

Drug resistance is dramatically restored by hedgehog inhibitors in CD34(+) leukemic cells

Masayoshi Kobune, Rishu Takimoto, Kazuyuki Murase, Satoshi Iyama, Tsutomu Sato, Shohei Kikuchi, Yutaka Kawano, Kohji Miyanishi, Yasushi Sato, Yoshiro Niitsu, Junji Kato

CANCER SCIENCE ( WILEY-BLACKWELL ) 100 ( 5 ) 948 - 955 2009.05 [Refereed]

Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide variety of human cancers and in cancer stem cells. However, the contribution of Hh signaling to leukemic cell regulation has remained unclear. In this study, we assessed the possibility that Hh pathway activation contributes to the survival and drug resistance of cluster of differentiation (CD)34(+) leukemia cells. Hh signaling in leukemic cell lines and primary leukemic cells was screened by reverse transcription - polymerase chain reaction (RT-PCR) and a Hh signaling reporter assay. We found that Hh signaling is active in several human acute myeloid leukemia (AML) cells, especially primary CD34(+) leukemic cells and cytokine-responsive CD34+ cell lines such as Kasumi-1, Kasumi-3 and TF-1. These CD34+ cells express the downstream effectors glioma-associated oncogene homolog (GLI)1 or GLI2, indicative of active Hh signaling. Moreover, inhibition of Hh signaling with the naturally derived Smoothened antagonist cyclopamine, endogenous Hh inhibitor hedgehog-interacting protein or anti-hedgehog neutralizing antibody induced apoptosis after 48 h of exposure, although these CD34(+) cell lines exhibited resistance to cytarabine (Ara-C). In contrast, cyclopamine failed to affect growth or survival in U937 and HL-60 cell lines that lack expression of Hh receptor components, confirming that the effect of Hh inhibition is specific. Furthermore, combination with 10 mu M cyclopamine significantly reduced drug resistance of CD34(+) cell lines and primary CD34(+) leukemic cells to Ara-C. These results suggest that aberrant Hh pathway activation is a feature of some CD34(+) myeloid leukemic cells and Hh inhibitors may have a therapeutic role in the treatment of AML. (Cancer Sci 2009; 100: 948-955).

DOI PubMed

Chronic idiopathic neutropenia associated with granular lymphocytic leukemia effectively treated with immunosuppressants

Yuko Fujimi, Yasuo Hirayama, Hiroyuki Kuroda, Toshiro Sakai, Yuichi Konuma, Kyuhei Kohda, Akihito Fujimi, Satoshi Iyama, Tsutomu Sato, Masayoshi Kobune, Rishu Takimoto, Junji Kato

Biotherapy 23 ( 3 ) 263 - 266 2009.05

A 64-year-old male was admitted to our hospital with diverticulitis of the large intestine, and a blood test detected neutropenia. Bone marrow aspiration found no hematological malignancy, and we considered idiopathic neutropenia. After he was injected with granulocyte colony-stimulating factor and antibiotics, abdominal pain and high fever disappeared. However, the neutropenia continued. One month after his hospitalization, we found monoclonal rearrangement of TCRβ and predominant granular lymphocyte in the peripheral blood. The diagnosis was granular lymphocytic leukemia (GLL) with neutropenia. After he was treated with immunosuppressants, the neutrophil count was normalized. We conclude that some cases of chronic idiopathic neutropenia are associated with GLL.

Treatment of hepatocellular carcinoma by AdAFPep/Rep, AdAFPep/p53, and 5-fluorouracil in mice

Tamotsu Sagawa, Yasuyuki Yamada, Minoru Takahashi, Yasushi Sato, Masayoshi Kobune, Rishu Takimoto, Junki Fukaura, Satoshi Iyama, Tsutomu Sato, Koji Miyanishi, Takuya Matsunaga, Tetsuji Takayama, Junji Kato, Katsunori Sasaki, Hirofumi Hamada, Yoshiro Niitsu

HEPATOLOGY ( JOHN WILEY & SONS INC ) 48 ( 3 ) 828 - 840 2008.09 [Refereed]

Although conditionally replicable adenovirus (CRAd) has been used in the clinical treatment of hepatocellular carcinoma (HCC), it suffers from the inherent drawback of having relatively low antitumor activity. Here, we have sought to overcome this drawback. First, we combined CRAd (AdAFPep/Rep) driven by a-fetoprotein enhancer/promoter (ATPep) with a replication-incompetent adenovirus carrying a p53 transgene that is also driven by AFPep. The synergism of this combination produced a significantly improved tumoricidal effect on the human HCC cell line Hep3B, which has a relatively short doubling time in comparison with other human HCC cell lines, through the transactivation of p53 by early region 1A transcribed by AdAFPep/Rep. This synergistic interaction was augmented by the addition of a subtumoricidal dose (0.5 mu g/mL) of 5-fluorouracil (5-FU), which enhanced p53 expression and facilitated the release of virions from tumor cells. When relatively large (10-mm-diameter) Hep3B tumors grown in nude mice were injected with the two viruses in combination, they showed significantly impaired growth in comparison with those treated with each virus separately. The growth suppression effect of the virus combination was enhanced by a low dose (600 mu g) of 5-FU. Survival of the tumor-bearing mice treated with these three agents was significantly longer than that of control mice. Moreover, the tumor completely disappeared with the repeated injection of these agents. Conclusion: This combination strategy holds promise for the treatment of relatively large and rapidly growing HCCs that may be encountered clinically.

DOI PubMed

[A case of hepatosplenic gammadelta T-cell lymphoma associated hemophagocytic syndrome].

Iyama S, Matsunaga T, Sato T, Sato Y, Sagawa T, Murase K, Kida M, Kobune M, Takimoto R, Kato J, Niitsu Y

Gan to kagaku ryoho. Cancer & chemotherapy ( 9 ) 35 1623 - 1627 2008.09 [Refereed]

PubMed

ヒト骨髄間質細胞は臍帯血CD34陰性細胞のCXCR4発現増強と長期造血再建能を誘導する

小船雅義, 村瀬和幸, 井山諭, 佐藤勉, 河野豊, 瀧本理修, 松永卓也, 加藤淳二

臨床血液 ( (一社)日本血液学会-東京事務局 ) 49 ( 9 ) 940 - 940 2008.09 [Refereed]

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Papers - IYAMA Satoshi