Details of a Researcher - TAKADA Kouichi

Papers - TAKADA Kouichi

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A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker

Masahiro Hirakawa, Yasushi Sato, Hiroyuki Ohnuma, Tetsuji Takayama, Tamotsu Sagawa, Takayuki Nobuoka, Keisuke Harada, Hiroshi Miyamoto, Yasuhiro Sato, Yasuo Takahashi, Shinich Katsuki, Michiaki Hirayama, Minoru Takahashi, Michihiro Ono, Masahiro Maeda, Kohichi Takada, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Rishu Takimoto, Masayoshi Kobune, Koichi Hirata, Junji Kato

CANCER CHEMOTHERAPY AND PHARMACOLOGY ( SPRINGER ) 71 ( 3 ) 789 - 797 2013.03 [Refereed]

The combination of docetaxel, cisplatin, and S-1 (DCS) chemotherapy is expected to be a promising regimen for advanced gastric cancer. This study was performed to evaluate the efficacy and safety of neoadjuvant DCS chemotherapy for locally advanced resectable gastric cancer. Patients with locally advanced gastric cancer received 2 courses of preoperative chemotherapy with S-1 (40 mg/m(2) b.i.d.) on days 1-14 and docetaxel (60 mg/m(2)) plus cisplatin (60 mg/m(2)) on day 8 every 3 weeks, followed by standard curative surgery within 4-8 weeks. The primary endpoint was R0 resectability. Expression of damage DNA binding protein complex subunit 2 (DDB2)/excision repair cross-complementing 1 (ERCC1) in the pretreated tumor tissues was examined by immunohistochemistry. A total of 43 patients received neoadjuvant chemotherapy. The response rate was 74.4 %, and disease control ratio was 100 %. Grade 4 neutropenia developed in 53.5 % of patients and febrile neutropenia in 16.3 %. Non-hematological grade 3/4 adverse events were anorexia (23.3 %), nausea (14.0 %), and diarrhea (23.3 %), but these were generally transient and manageable. The proportion of R0 resections in the 43 eligible patients was 90.7 %, and a pathological response was found in 65.9 % of patients. There were no treatment-related deaths and no major surgical complications. The accuracy of the combination of DDB2 and ERCC1 expression for predicting chemoresistance was 82.5 %. Preoperative treatment with DCS combination for locally advanced gastric cancer demonstrated a sufficient R0 resection rate and a good pathological response with manageable toxicities. The DDB2/ERCC1-high phenotype, as determined by immunohistochemistry, may be useful predictor of resistance to DCS chemotherapy.

DOI PubMed

急性胆嚢炎を合併した巨大肝細胞癌(stage IVA)に対して集学的治療により治癒が得られた1例

河野豊, 宮西浩嗣, 田村文人, 堀口拓人, 田中信悟, 高田弘一, 林毅, 佐藤勉, 佐藤康史, 瀧本理修, 小船雅義, 加藤淳二

肝臓 ( (一社)日本肝臓学会 ) 53 ( Suppl.3 ) A962 - A962 2012.10 [Refereed]

Intermittent administration of recombinant human soluble thrombomodulin successfully controlled chronic disseminated intravascular coagulation in a patient with dissecting aortic aneurysm on an outpatient basis

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

BLOOD COAGULATION & FIBRINOLYSIS ( LIPPINCOTT WILLIAMS & WILKINS ) 23 ( 6 ) 548 - 550 2012.09 [Refereed]

Chronic disseminated intravascular coagulation (DIC) is a rare but life-threatening complication of dissecting aortic aneurysm. Although anticoagulant therapy may often proves effective for controlling DIC itself, patients would have to be hospitalized for a long period due to continuous infusion therapy. Subcutaneous injection of a highly concentrated preparation of heparin calcium may offer one alternative treatment for DIC; however, daily subcutaneous use of heparin for the treatment of DIC has impaired quality of life (QOL). The other alternative therapy is intravenous administration of recombinant human soluble thrombomodulin (rTM), which includes the active extracellular domain of thrombomodulin. Reportedly, rTM effectively resolves DIC by only 6 consecutive days of administration; however, how frequently rTM should be administered after the resolution of chronic DIC to have good control of it has been unclear. We report herein a case of chronic DIC complicated with dissecting aortic aneurysm, whose resolution of chronic DIC achieved by 6 consecutive days of rTM has been maintained by once a week administration of rTM on an outpatient basis. Blood Coagul Fibrinolysis 23:548-550 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

DOI PubMed

Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms

M. Kobune, S. Iyama, S. Kikuchi, H. Horiguchi, T. Sato, K. Murase, Y. Kawano, K. Takada, K. Ono, Y. Kamihara, T. Hayashi, K. Miyanishi, Y. Sato, R. Takimoto, J. Kato

BLOOD CANCER JOURNAL ( NATURE PUBLISHING GROUP ) 2 2012.09 [Refereed]

Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide variety of human cancers including cancer stem cells. However, involvement of the Hh-signaling system in the bone marrow (BM) microenvironment during the development of myeloid neoplasms is unknown. In this study, we assessed the expression of Hh-related genes in primary human CD34(+) cells, CD34(+) blastic cells and BM stromal cells. Both Indian Hh (Ihh) and its signal transducer, smoothened (SMO), were expressed in CD34(+) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)-derived cells. However, Ihh expression was relatively low in BM stromal cells. Remarkably, expression of the intrinsic Hh-signaling inhibitor, human Hh-interacting protein (HHIP) in AML/MDS-derived stromal cells was markedly lower than in healthy donor-derived stromal cells. Moreover, HHIP expression levels in BM stromal cells highly correlated with their supporting activity for SMO+ leukemic cells. Knockdown of HHIP gene in stromal cells increased their supporting activity although control cells marginally supported SMO+ leukemic cell proliferation. The demethylating agent, 5-aza-2'-deoxycytidine rescued HHIP expression via demethylation of HHIP gene and reduced the leukemic cell-supporting activity of AML/MDS-derived stromal cells. This indicates that suppression of stromal HHIP could be associated with the proliferation of AML/MDS cells.

DOI

Improvement of iron-mediated oxidative DNA damage in patients with transfusion-dependent myelodysplastic syndrome by treatment with deferasirox

Shohei Kikuchi, Masayoshi Kobune, Satoshi Iyama, Tsutomu Sato, Kazuyuki Murase, Yutaka Kawano, Kohichi Takada, Kaoru Ono, Yumiko Kaneko, Koji Miyanishi, Yasushi Sato, Tsuyoshi Hayashi, Rishu Takimoto, Junji Kato

FREE RADICAL BIOLOGY AND MEDICINE ( ELSEVIER SCIENCE INC ) 53 ( 4 ) 643 - 648 2012.08 [Refereed]

Myelodysplastic syndrome (MDS) is characterized by dysplastic and ineffective hematopoiesis, peripheral blood cytopenias, and a risk of leukemic transformation. Most MDS patients eventually require red blood cell (RBC) transfusions for anemia and consequently develop iron overload. Excess free iron in cells catalyzes generation of reactive oxygen species that cause oxidative stress, including oxidative DNA, damage. However, it is uncertain how iron-mediated oxidative stress affects the pathophysiology of MDS. This study included MDS patients who visited our university hospital and affiliated hospitals (n=43). Among them, 13 patients received iron chelation therapy when their serum ferritin (SF) level was greater than 1000 ng/mL or they required more than 20 RBC transfusions (or 100 rnL/kg of RBC). We prospectively analyzed 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in peripheral blood mononuclear cells (PBMC) obtained from MDS patients before and after iron chelator, deferasirox, administration. We showed that the 8-OHdG levels in MDS patients were significantly higher than those in healthy volunteers and were positively correlated with SF and chromosomal abnormalities. Importantly, the 8-OHdG levels in PBMC of MDS patients significantly decreased after deferasirox administration, suggesting that iron chelation reduced oxidative DNA damage. Thus, excess iron could contribute to the pathophysiology of MDS and iron chelation therapy could improve the oxidative DNA damage in MDS patients. (C) 2012 Elsevier Inc. All rights reserved.

DOI PubMed

Targeting Anticancer Drug Delivery to Pancreatic Cancer Cells Using a Fucose-Bound Nanoparticle Approach

Makoto Yoshida, Rishu Takimoto, Kazuyuki Murase, Yasushi Sato, Masahiro Hirakawa, Fumito Tamura, Tsutomu Sato, Satoshi Iyama, Takahiro Osuga, Koji Miyanishi, Kohichi Takada, Tsuyoshi Hayashi, Masayoshi Kobune, Junji Kato

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 7 ( 7 ) e39545 2012.07 [Refereed]

Owing to its aggressiveness and the lack of effective therapies, pancreatic ductal adenocarcinoma has a dismal prognosis. New strategies to improve treatment and survival are therefore urgently required. Numerous fucosylated antigens in sera serve as tumor markers for cancer detection and evaluation of treatment efficacy. Increased expression of fucosyltransferases has also been reported for pancreatic cancer. These enzymes accelerate malignant transformation through fucosylation of sialylated precursors, suggesting a crucial requirement for fucose by pancreatic cancer cells. With this in mind, we developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specifically to cancer cells. L-fucose-bound liposomes containing Cy5.5 or Cisplatin were effectively delivered into CA19-9 expressing pancreatic cancer cells. Excess L-fucose decreased the efficiency of Cy5.5 introduction by L-fucose-bound liposomes, suggesting L-fucose-receptor-mediated delivery. Intravenously injected L-fucose-bound liposomes carrying Cisplatin were successfully delivered to pancreatic cancer cells, mediating efficient tumor growth inhibition as well as prolonging survival in mouse xenograft models. This modality represents a new strategy for pancreatic cancer cell-targeting therapy.

DOI PubMed

Prognostic significance of serum ferritin level at diagnosis in myelodysplastic syndrome

Shohei Kikuchi, Masayoshi Kobune, Satoshi Iyama, Tsutomu Sato, Kazuyuki Murase, Yutaka Kawano, Kohichi Takada, Kaoru Ono, Tsuyoshi Hayashi, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Junji Kato

INTERNATIONAL JOURNAL OF HEMATOLOGY ( SPRINGER TOKYO ) 95 ( 5 ) 527 - 534 2012.05 [Refereed]

Myelodysplastic syndrome (MDS) is characterized by peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Elevated serum ferritin (SF), due to ineffective erythropoiesis and increased iron absorption from the gut, is often observed in non-transfused MDS patients, suggesting involvement of iron overload in its pathogenesis. However, the prognostic value of the baseline SF is unclear. We evaluated baseline SF levels in non-transfused MDS patients. The SF level was significantly higher in the 47 MDS patients in this study than in the healthy controls ( < 0.001). The SF level of higher-risk MDS patients (int-2/high) was significantly higher than that of the lower-risk MDS patients (low/int-1) (467 +/- A 354 vs. 277 +/- A 372 ng/ml, < 0.001). The SF level in MDS patients with chromosomal abnormality was significantly higher than that in patients with normal karyotype. When patients were divided into the low SF group (< 500 ng/ml) and high SF group (a parts per thousand yen500 ng/mL), the survival time was significantly longer in the former group than the latter group (118.8 vs. 10.2 M, = 0.002). Further, leukemia-free survival (LFS) was significantly longer in the low SF group than the high SF group ( = 0.010). Baseline SF level may, therefore, be a prognostic factor for overall survival and LFS in MDS patients.

DOI PubMed

Successful Treatment by Fibrin Glue Sealant for Pneumothorax with Chronic GVHD Resistant to Autologous Blood Patch Pleurodesis

Satoshi Iyama, Tsutomu Sato, Kazuyuki Murase, Shohei Kikuchi, Yusuke Kamihara, Kaoru Ono, Kohichi Takada, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Takuro Obama, Masahiro Miyajima, Atsushi Watanabe, Tetsuya Higami, Yasuo Hirayama, Junji Kato

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE ) 51 ( 15 ) 2011 - 2014 2012 [Refereed]

Pneumothorax associated with chronic graft-versus-host disease (cGVHD) after stem cell transplantation is a rare complication. Autologous blood has been used successfully for pleurodesis, which was less toxic than chemical agents. However, when pneumothorax is resistant to pleurodesis, no other procedure is more effective and conservative. Here, we describe a case of myelodysplastic syndromes complicated with cGVHD-related pneumothorax. His pneumothorax has been resistant to pleurodesis using autologous blood and was treated successfully with fibrin glue sealant. In our limited experience, we believe the best success could be achieved when this method is used to treat persistent pneumothorax with cGVHD.

DOI PubMed

What I do, study, and think as an information professional (32) : What I expect from information professionals

YAMADA Koji

Journal of Information Processing and Management ( Japan Science and Technology Agency ) 54 ( 10 ) 674 - 675 2012

DOI CiNii

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

非アルコール性脂肪性肝炎における鉄吸収亢進機序と除鉄療法の有用性の検討

宮西浩嗣, 河野豊, 小船雅義, 高田弘一, 永島裕之, 佐藤康史, 瀧本理修, 加藤淳二

アルコールと医学生物学 ( (株)響文社 ) 29 142 - 146 2010.04 [Refereed]

肝生検を施行し、組織学的に診断された非アルコール性脂肪性肝炎(NASH)患者22例を対象に、鉄吸収調節因子であるペプシジン、ヘモジュベリンと十二指腸鉄吸収関連分子の発現量の測定ならびにin vitroにおいてNASH患者血清が十二指腸鉄吸収関連分子発現に及ぼす影響を解析し、NASHにおける鉄吸収亢進機序を検討した。また、1年以上除鉄療法を継続したNASH患者の鉄代謝とアディポサイトカイン値を追跡し除鉄療法の有用性を検討した。コントロール群として用いたRNAは鉄代謝マーカーに異常がない転移性肝癌5例と肝エキノコッカス症1例の外科的に切除された肝臓の非病変部より抽出した。NASH患者では健常人に比較して血清ペプシジン濃度は有意に増加していた。NASH患者の肝臓におけるペプシジン、ヘモジュベリンRNA発現はコントロール群のそれと比較して有意に増加していた。両者には正の相関が認められた。NASH患者十二指腸ではDMT1、Dcyt b、HephaestinのRNA発現がコントロール群と比較して有意に増加していた。ferroportin-1のRNA発現量は有意差が認められなかった。NASH患者血清でCaco-2細胞を培養したところ、ferroportin-1、Dcyt bとHephaestinのRNA発現がコントロール血清で培養したものと差がなかったが、DMT1のRNA発現は有意に増加していた。NASH患者の除鉄療法を施行し、1年以上の経過を観察したところ、肝細胞障害程度の改善、血清フェリチン値低下、アディポネクチンの増加が認められた。

[Cholangiocarcinoma with bile duct adenoma and hamartoma-like lesion in the bile duct].

Sho Takahashi, Kohichi Takada, Yutaka Kawano, Koji Miyanishi, Hirotoshi Ishiwatari, Tsuyoshi Hayashi, Tamotsu Sagawa, Tsutomu Sato, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Ganji Kuroiwa, Michiaki Hirayama, Hirotoshi Tobioka, Kouichi Hirata, Mutsuko Omatsu, Tadashi Hasegawa, Junji Kato

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology ( 3 ) 107 ( 3 ) 461 - 9 2010.03 [Refereed] [Domestic journal]

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

DOI PubMed

進行膵癌に対する動注化学療法の効果の検討

宮西浩嗣, 河野豊, 高田弘一, 林毅, 石渡裕俊, 吉田真誠, 菊地尚平, 永島裕之, 加藤淳二

IVR: Interventional Radiology ( (一社)日本インターベンショナルラジオロジー学会 ) 24 ( 4 ) 406 - 406 2009.10 [Refereed]

Suppressive effect of sulindac on branch duct-intraductal papillary mucinous neoplasms.

Tsuyoshi Hayashi, Hirotoshi Ishiwatari, Hideyuki Ihara, Yutaka Kawano, Koichi Takada, Koji Miyanishi, Masayoshi Kobune, Rishu Takimoto, Tomoko Sonoda, Tetsuji Takayama, Junji Kato, Yoshiro Niitsu

Journal of gastroenterology ( SPRINGER TOKYO ) 44 ( 9 ) 964 - 75 2009 [Refereed] [Domestic journal]

BACKGROUND: When considering surgery for branch duct-intraductal papillary mucinous neoplasms (BD-IPMNs) with suspected malignancy, it should be recognized that these lesions are frequently multifocal and are usually found in elderly patients with potential comorbidities that could affect the outcome of surgery. Clinical trials of chemoprevention have been conducted for a wide variety of malignancies. METHODS: Twenty-two BD-IPMN patients participated in the trial at our institution from June 2004 to January 2007. Ten of the 22 patients who rejected surgical therapy although their lesions or clinical symptoms met the criteria for surgical resection of the International Association of Pancreatology guidelines were assigned to the treatment group. Sulindac (150 mg twice daily) and omeprazole (20 mg once daily) were administered to these patients for 18 months. The remaining 12 patients comprised the control group. Branch duct diameter and mural nodule heights were monitored by either magnetic resonance cholangiopancreatography (MRCP) or computed tomography (CT) and by endoscopic ultrasonography (EUS). RESULTS: Both branch duct diameter and mural nodule height of BD-IPMNs in the treatment group were significantly reduced, while those in the control group were unchanged. Immunohistochemical staining for cyclooxygenase-1 and -2 was negative in hyperplasia, adenoma and carcinoma portions of resected pancreatic specimens but was clearly positive for glutathione-S-transferase pi (GST-pi), suggesting that GST-pi is a putative target molecule for sulindac. CONCLUSIONS: Although a larger scale randomized controlled study is needed in future, the present results suggest the promise of chemoprevention of carcinoma derived from BD-IPMNs by sulindac.

DOI PubMed

[Effective CDDP arterial infusion with DSM for liver metastasis of malignant melanoma complicating DIC due to intratumoral hemorrhage--a case report].

Kohichi Takada, Junji Kato, Yutaka Kawano, Sho Takahashi, Tsuyoshi Hayashi, Hirotoshi Ishiwatari, Koji Miyanishi, Rishu Takimoto, Masayoshi Kobune, Tamotsu Sagawa, Tsutomu Sato, Yasushi Sato, Toshiharu Yamashita, Hiroshi Natori, Yoshiro Niitsu

Gan to kagaku ryoho. Cancer & chemotherapy ( 10 ) 35 ( 10 ) 1803 - 5 2008.10 [Refereed] [Domestic journal]

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

PubMed

腫瘍内出血によりDICが惹起された悪性黒色腫多発肝転移にDSM併用CDDP動注化学療法が有効であった1例

高田弘一, 加藤淳二, 河野豊, 高橋祥, 林毅, 石渡裕俊, 宮西浩嗣, 瀧本理修, 小船雅義, 佐川保, 佐藤勉, 佐藤康史, 山下利春, 名取博, 新津洋司郎

癌と化学療法 ( (株)癌と化学療法社 ) 35 ( 10 ) 1803 - 1805 2008.10 [Refereed]

症例は65歳、男性。2003年よりメラノーマstage IIBと診断され、当院皮膚科にて化学療法を施行されてきたが肝転移の制御が困難となり、当科へ紹介された。2006年よりCDDPを用いた肝動注化学療法を開始したが、2007年5月全身倦怠感および貧血、血小板減少のため緊急入院となった。造影CTで肝転移は増大していた。造影超音波では腫瘍辺縁部に結節状の造影所見を認めた。以上より腫瘍内出血によるDICと診断した。出血の原因と考えられる病変は多血性であったため、肝転移に対する治療としてDSM併用CDDP動注化学療法を施行した。同治療によりDICが改善した。メラノーマ肝転移は、経過中に腫瘍内出血を来しDICを発症する可能性があり注意を要する。また、メラノーマ肝転移に対してDSM併用動注化学療法が有効である可能性が示唆された。(著者抄録)

Interaction with human stromal cells enhances CXCR4 expression and engraftment of cord blood Lin(-)CD34(-) cells

Masayoshi Kobune, Yutaka Kawano, Sho Takahashi, Kohichi Takada, Kazuyuki Murase, Satosi Iyama, Tsutomu Sato, Rishu Takimoto, Yoshiro Niitsu, Junji Kato

EXPERIMENTAL HEMATOLOGY ( ELSEVIER SCIENCE INC ) 36 ( 9 ) 1121 - 1131 2008.09 [Refereed]

Objective. Transplantation of hematopoietic stem cells (HSCs) is usually accomplished through intravenous injection, a complex process that requires recognition of bone marrow vasculature and migration to a supportive microenvironment. Hence, some populations of HSCs, including cord blood (CB) Lin(-)CD34(-) stem cells, do not engraft well in bone marrow (BM) of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. In this study, we examined the effect of human stromal interactions on the properties of CB Lin(-)CD34(-) cells. Materials and Methods. CD34 and CXCR4 expression on fresh CB Lin(-)CD34(-) cells and CB Lin(-)CD34(-) cells cocultured with human stromal cells were analyzed. Homing activity and engraftment of these cells were assessed using NOD/SCID mice. In an attempt to identify the stromal CXCR4-inducing factor, CB Lin(-)CD34(-) cells were cocultured with a noncontact culture system in the presence of several inhibitors. Result. Coculture with human stromal cells induced expression of CD34 and CXCR4 on CB Lin(-)CD34(-) cells. CXCR4 expression on CB Lin(-)CD34(-) cells was induced even in the noncontact culture condition, suggesting that this CXCR4-inducing factor is soluble. Moreover, CXCR4 induction was inhibited by the soluble Wnt inhibitor DKK1. Furthermore, these cells acquired homing activity and engrafted in the BM of NOD/SCID mice after intravenous injection. Conclusion. These findings maybe useful for understanding the role of stromal cells in homing and engraftment of HSCs. (C) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

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