Details of a Researcher - TAKADA Kouichi

Papers - TAKADA Kouichi

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低分子化合物CP-31398は多発性骨髄腫に対して活性酸素種依存的なアポトーシスを誘導する

在原洋平, 高田弘一, 神原悠輔, 河野豊, 早坂尚貴, 中村元, 菊地尚平, 村瀬和幸, 井山諭, 池田博, 佐藤勉, 宮西浩嗣, 小船雅義, 加藤淳二

International Journal of Myeloma ( 日本骨髄腫学会 ) 7 ( 1 ) 76 - 76 2017.04 [Refereed]

A case of intussusceptions at two parts of the ileum caused by an ileus tube

Yutaka Okagawa, Kohichi Takada, Hiroki Sakamoto, Takumi Miura, Shigeki Abeshima, Junji Kato

Journal of Japanese Society of Gastroenterology ( Japanese Society of Gastroenterology ) 114 ( 6 ) 1001 - 1007 2017 [Refereed]

An 87-year-old woman was admitted to our hospital for paralytic ileus, and she was treated using an ileus tube. Although her symptoms improved, abdominal fullness developed again on day 3 after ileus tube insertion. Abdominal computed tomography indicated intussusceptions at the ileum and the terminal part of the ileum therefore, an emergency surgery was performed. During the surgery, antegrade intussusceptions were found in the ileum 60cm from the ileocecal valve and the terminal part of the ileum into the ascending colon. The intussusception of the anal side was resolved by manual reduction, but the oral side needed a partial resection of small bowel because of the presence of necrosis. There were no lesions, such as tumors, at the intussusceptions sites. Therefore, the two intussusceptions were thought to be caused by the ileus tube. We diagnosed a rare case of intussusceptions in the two parts of the ileum as a complication of the placement of an ileus tube.

PubMed

A case of gastric perforation caused by chestnut bezoars

OKAGAWA Yutaka, TAKADA Kohichi, ARIHARA Yohei, KATO Junji

Nippon Shokakibyo Gakkai Zasshi ( The Japanese Society of Gastroenterology ) 114 ( 10 ) 1830 - 1835 2017

A 65-year-old man was admitted under emergency to our hospital because of abdominal pain. His current medication history did not include steroids or nonsteroidal antiinflammatory drugs. He had taken an eradication agent for Helicobacter pylori, and his serum was negative for H. pylori IgG antibody. Abdominal computed tomography indicated gastric perforation;therefore, emergency surgery was performed. Two weeks later, esophagogastroduodenoscopy revealed a gastric ulcer on the lesser curvature of the gastric angle and bezoars. The gastric perforation was thought to be caused by the bezoars. The bezoars were successfully treated with endoscopic therapy using Coca-Cola^®. The bezoars included over 98% tannin, and the patient had frequently consumed chestnuts. We thus diagnosed a rare case of gastric perforation caused by chestnut bezoars.

DOI CiNii

A phase II trial of small-dose bortezomib, lenalidomide and dexamethasone (sVRD) as consolidation/maintenance therapy in patients with multiple myeloma

Soushi Ibata, Tsutomu Sato, Hiroyuki Kuroda, Yasuhiro Nagamachi, Satoshi Iyama, Akihito Fujimi, Yusuke Kamihara, Yuichi Konuma, Masahiro Yoshida, Ayumi Tatekoshi, Akari Hashimoto, Hiroto Horiguchi, Kaoru Ono, Kazuyuki Murase, Kohichi Takada, Koji Miyanishi, Masayoshi Kobune, Yasuo Hirayama, Junji Kato

CANCER CHEMOTHERAPY AND PHARMACOLOGY ( SPRINGER ) 78 ( 5 ) 1041 - 1049 2016.11 [Refereed]

Consolidation/maintenance therapy induces deep remission in patients with multiple myeloma (MM); however, the most suitable regimen has been under investigation. The combination therapy with bortezomib, lenalidomide and dexamethasone (VRD) is a powerful regimen for relapsed/refractory as well as newly diagnosed MM as an induction therapy. However, severe adverse events (AEs) may become a problem when VRD is introduced without dose reduction as a consolidation/maintenance therapy. In this single-arm phase II study, we evaluated the efficacy of small-dose VRD regimen (sVRD) in the consolidation/maintenance setting. Sixteen patients who had partial response (PR) or better after any induction therapy were enrolled. Patients received at least six 28-day cycles of subcutaneous bortezomib (1.3 mg/m(2) on days 1 and 15), lenalidomide (10 mg on days 1-21) and dexamethasone (40 mg on days 1, 8, 15 and 22). The overall response rate and the complete response (CR) rate were 100 and 43.8 %, respectively. In particular, one patient with CR and two patients with very good PR at enrollment achieved stringent CR during 6 courses of sVRD. With a median follow-up time of 29.4 months, the median progression-free survival (PFS) and overall survival (OS) were not reached, while the PFS and OS rates at 2.5 years were 66.6 and 77.3 %, respectively. Univariate analysis demonstrated that disease progression as a reason for discontinuation of sVRD had a negative impact on OS. There were no grade 3 or 4 hematologic or nonhematologic AEs. Our sVRD regimen as a consolidation/maintenance therapy was highly effective and well tolerable.

DOI PubMed

Relationship Between Increased Fucosylation and Metastatic Potential in Colorectal Cancer

Takahiro Osuga, Rishu Takimoto, Michihiro Ono, Masahiro Hirakawa, Makoto Yoshida, Yutaka Okagawa, Naoki Uemura, Yohei Arihara, Yasushi Sato, Fumito Tamura, Tsutomu Sato, Satoshi Iyama, Koji Miyanishi, Kohichi Takada, Tsuyoshi Hayashi, Masayoshi Kobune, Junji Kato

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE ( OXFORD UNIV PRESS INC ) 108 ( 9 ) 2016.09 [Refereed]

Background: Fucose is utilized for the modification of different molecules involved in blood group determination, immunological reactions, and signal transduction pathways. We have recently reported that enhanced activity of the fucosyltransferase 3 and/or 6 promoted TGF-beta-mediated epithelial mesenchymal transition and was associated with increased metastatic potential of colorectal cancer (CRC), suggesting that fucose is required by CRC cells. With this in mind, we examined requirement of L-fucose in CRC cells and developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specific to CRC. Methods: In this study, we first examined the expression of fucosylated proteins in 50cases of CRC by immunochistochemical staining with biotinylated Aleuria aurantia lectin (AAL). Then we carried out an L-fucose uptake assay using three CRC cell lines. Finally, we developed fucose-bound nanoparticles as vehicles for the delivery of an anticancer drug, SN38, and examined tumor growth inhibition in mouse xenograft model (n = 6 mice per group). All statistical tests were two-sided. Results: We found a statistically significant relationship between vascular invasion, clinical stage, and intensity score of AAL staining (P <= .02). L-fucose uptake assay revealed that L-fucose incorporation, as well as fucosylated protein release, was high in cells rich in fucosylated proteins. L-fucose-bound liposomes effectively delivered Cy5.5 into CRC cells. The excess of L-fucose decreased the efficiency of Cy5.5 uptake through L-fucose-bound liposomes, suggesting an L-fucose receptor dependency. Intravenously injected, L-fucose-bound liposomes carrying SN38 were successfully delivered to CRC cells, mediating efficient tumor growth inhibition (relative tumor growth ratio: no treatment group [NT], 8.29 +/- 3.09; SN38-treated group [SN38], 3.53 +/- 1.47; liposome-carrying, SN38-treated group [F0], 3.1 +/- 1.39; L-fucose-bound, liposome-carrying, SN38-treated group [F50], 0.94 +/- 0.89; F50 vs NT, P = .003; F50 vs SN38, P = .02, F50 vs F0, P = .04), as well as prolonging survival of mouse xenograft models (log-rank test, P < .001). Conclusions: Thus, fucose-bound liposomes carrying anticancer drugs provide a new strategy for the treatment of CRC patients.

DOI PubMed

[Treatment Outcomes of Adult-Onset Ewing Sarcoma: A Single-Center Retrospective Study of Five Cases].

Kazuyuki Murase, Kohichi Takada, Yusuke Kamihara, Makoto Usami, Masahiro Yoshida, Ayumi Tatekoshi, Akari Hashimoto, Yohei Arihara, Naotaka Hayasaka, Shogo Miura, Satoshi Iyama, Tsutomu Sato, Yasushi Sato, Koji Miyanishi, Masayoshi Kobune, Makoto Emori, Mitsunori Kaya, Toshihiko Yamashita, Shintaro Sugita, Tadashi Hasegawa, Junji Kato

Gan to kagaku ryoho. Cancer & chemotherapy 43 ( 8 ) 1015 - 8 2016.08 [Refereed] [Domestic journal]

UNLABELLED: We report the treatment outcomes of 5 cases of adult-onset Ewing sarcoma(ES)managed between 2011 and 2014. We examined prognostic factors including the primary lesion, tumor size, metastatic status, and serum LDH levels. RESULTS: The locations of the primary lesions included the limbs in 1 case and the trunk in 4; the cases in the trunk had a worse prognosis than that in the limbs. Tumor size was greater than 8 cm in only 1 patient, who also displayed evidence of metastases at presentation and high LDH levels. All the patients received chemotherapy consisting of alternating vincristine, doxorubicin, and cyclophosphamide(VDC)and etoposide and ifosfamide(IE). Surgery was selected for the treatment of 4 patients, and radiotherapy was administered to 1 patient for local treatment of the tumor. A median follow-up duration of 31.6 months revealed the 2-year overall survival rate and progression-free survival rate to be 80.0%. CONCLUSIONS: The prognosis of patients with adult-onset ES is poor; however, combined modality therapy, including VDC-IE, was demonstrated to improve the outcome of patients in the present study. Nevertheless, the patient with tumor size exceeding 8 cm, metastasis, and high LDH levels, relapsed 1 year after treatment, as reported previously. Further investigation is required to clarify the factors affecting prognosis in adults, and to develop effective therapies for patients with a poor prognosis.

PubMed

Relationship Between Increased Fucosylation and Metastatic Potential in Colorectal Cancer

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE ( OXFORD UNIV PRESS INC ) 108 ( 8 ) 2016.08 [Refereed]

Background: Fucose is utilized for the modification of different molecules involved in blood group determination, immunological reactions, and signal transduction pathways. We have recently reported that enhanced activity of the fucosyltransferase 3 and/or 6 promoted TGF-beta-mediated epithelial mesenchymal transition and was associated with increased metastatic potential of colorectal cancer (CRC), suggesting that fucose is required by CRC cells. With this in mind, we examined requirement of L-fucose in CRC cells and developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specific to CRC. Methods: In this study, we first examined the expression of fucosylated proteins in 50 cases of CRC by immunochistochemical staining with biotinylated Aleuria aurantia lectin (AAL). Then we carried out an L-fucose uptake assay using three CRC cell lines. Finally, we developed fucose-bound nanoparticles as vehicles for the delivery of an anticancer drug, SN38, and examined tumor growth inhibition in mouse xenograft model (n = 6 mice per group). All statistical tests were two-sided. Results: We found a statistically significant relationship between vascular invasion, clinical stage, and intensity score of AAL staining (P <= .02). L-fucose uptake assay revealed that L-fucose incorporation, as well as fucosylated protein release, was high in cells rich in fucosylated proteins. L-fucose-bound liposomes effectively delivered Cy5.5 into CRC cells. The excess of L-fucose decreased the efficiency of Cy5.5 uptake through L-fucose-bound liposomes, suggesting an L-fucose receptor dependency. Intravenously injected, L-fucose-bound liposomes carrying SN38 were successfully delivered to CRC cells, mediating efficient tumor growth inhibition (relative tumor growth ratio: no treatment group [NT], 8.29 +/- 3.09; SN38-treated group [SN38], 3.53 +/- 1.47; liposome-carrying, SN38-treated group [F0], 3.1 +/- 1.39; L-fucose-bound, liposome-carrying, SN38-treated group [F50], 0.94 +/- 0.89; F50 vs NT, P = .003; F50 vs SN38, P = .02, F50 vs F0, P = .04), as well as prolonging survival of mouse xenograft models (log-rank test, P < .001). Conclusions: Thus, fucose-bound liposomes carrying anticancer drugs provide a new strategy for the treatment of CRC patients.

DOI PubMed

Targeting Notch-1 positive acute leukemia cells by novel fucose-bound liposomes carrying daunorubicin.

Michihiro Ono, Rishu Takimoto, Takahiro Osuga, Yutaka Okagawa, Masahiro Hirakawa, Makoto Yoshida, Yohei Arihara, Naoki Uemura, Naoki Hayasaka, Shogo Miura, Teppei Matsuno, Fumito Tamura, Yasushi Sato, Tsutomu Sato, Satoshi Iyama, Koji Miyanishi, Kohichi Takada, Masayoshi Kobune, Junji Kato

Oncotarget 7 ( 25 ) 38586 - 38597 2016.06 [Refereed] [International journal]

Complete remission by induction therapy in acute myelogenous leukemia (AML) can be achieved due to improvements in supportive and optimized therapy. However, more than 20% of patients will still need to undergo salvage therapy, and most will have a poor prognosis. Determining the specificity of drugs to leukemia cells is important since this will maximize the dose of chemotherapeutic agents that can be administered to AML patients. In turn, this would be expected to lead to reduced drug toxicity and its increased efficacy. We targeted Notch-1 positive AML cells utilizing fucose-bound liposomes, since activation of Notch-1 is required for O-fucosylation. Herein, we report that intravenously injected, L-fucose-bound liposomes containing daunorubicin can be successfully delivered to AML cells that express fucosylated antigens. This resulted in efficient tumor growth inhibition in tumor-bearing mice and decreased proliferation of AML patient-derived leukemia cells. Thus, biological targeting by fucose-bound liposomes that takes advantage of the intrinsic characteristics of AML cells could be a promising new strategy for Notch-1 positive-AML treatment.

DOI PubMed

肛門周囲の感覚障害で発症し、前立腺生検にて診断に至った血管内リンパ腫(IVL)の1例

齋藤太郎, 中村祐貴, 鈴木秀一郎, 津田笑子, 林貴士, 齊藤正樹, 久原真, 川又純, 下濱俊, 村瀬和幸, 高田弘一

臨床神経学 ( (一社)日本神経学会 ) 56 ( 6 ) 451 - 451 2016.06

Isoform D of vascular endothelial growth factor in systemic capillary leak syndrome: a case report.

Soushi Ibata, Tsutomu Sato, Kohichi Takada, Ayumi Tatekoshi, Akari Hashimoto, Yusuke Kamihara, Wataru Jomen, Hiroto Horiguchi, Kaoru Ono, Kazuyuki Murase, Satoshi Iyama, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Junji Kato

Journal of medical case reports 10 125 - 125 2016.05 [Refereed] [International journal]

BACKGROUND: Systemic capillary leak syndrome is a rare condition characterized by episodic attacks of hypovolemia due to systemic capillary hyperpermeability, which results in profound hypotension and edema. Although the implication of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 has been suggested, the pathogenesis of systemic capillary leak syndrome remains unclear. In this report, we describe a case of systemic capillary leak syndrome in which serum isoform D of vascular endothelial growth factor was elevated. To the best of our knowledge, this is the first reported case of systemic capillary leak syndrome in which isoform D of vascular endothelial growth factor is suggested as the plausible biomarker. CASE PRESENTATION: A 41-year-old Japanese man was transferred to our emergency department. He was hypotensive, tachycardic, and edematous over the trunk and all four limbs. He received aggressive intravenous fluid therapy and underwent fasciotomy of the right forearm to prevent muscle necrosis. A diagnosis of systemic capillary leak syndrome was suspected. The presence of serum monoclonal immunoglobulin G and κ light chain supported this diagnosis. Prevention of hypotensive crises was unsuccessfully attempted with theophylline, intravenous immunoglobulin, high-dose dexamethasone, bortezomib, melphalan, and prednisolone; however, the patient's attacks dramatically disappeared after the introduction of thalidomide. The serum of the patient was stored soon after the onset of hypotensive crisis and analyzed to profile possible mediators responsible for the capillary leak. The concentration of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 were all within normal ranges. Meanwhile, we found that isoform D of vascular endothelial growth factor was elevated, which was normalized after the introduction of thalidomide. CONCLUSIONS: In our patient, isoform D of vascular endothelial growth factor (instead of vascular endothelial growth factor) may have been a causative factor of hypotensive crises, since isoform D contributes to vascular endothelial growth factor receptor-2 signaling, which is the major mediator of the permeability-enhancing effects of vascular endothelial growth factor. We suggest the measurement of isoform D of vascular endothelial growth factor in patients with systemic capillary leak syndrome in whose serum vascular endothelial growth factor is not elevated.

DOI PubMed

Extracellular vesicle miR-7977 is involved in hematopoietic dysfunction of mesenchymal stromal cells via poly(rC) binding protein 1 reduction in myeloid neoplasms

Hiroto Horiguchi, Masayoshi Kobune, Shohei Kikuchi, Masahiro Yoshida, Masaki Murata, Kazuyuki Murase, Satoshi Iyama, Kohichi Takada, Tsutomu Sato, Kaoru Ono, Akari Hashimoto, Ayumi Tatekoshi, Yusuke Kamihara, Yutaka Kawano, Koji Miyanishi, Norimasa Sawada, Junji Kato

HAEMATOLOGICA ( FERRATA STORTI FOUNDATION ) 101 ( 4 ) 437 - 447 2016.04 [Refereed]

The failure of normal hematopoiesis is observed in myeloid neoplasms. However, the precise mechanisms governing the replacement of normal hematopoietic stem cells in their niche by myeloid neoplasm stem cells have not yet been clarified. Primary acute myeloid leukemia and myelodysplastic syndrome cells induced aberrant expression of multiple hematopoietic factors including Jagged-1, stem cell factor and angiopoietin-1 in mesenchymal stem cells even in non-contact conditions, and this abnormality was reverted by extracellular vesicle inhibition. Importantly, the transfer of myeloid neoplasm-derived extracellular vesicles reduced the hematopoietic supportive capacity of mesenchymal stem cells. Analysis of extracellular vesicle microRNA indicated that several species, including miR-7977 from acute myeloid leukemia cells, were higher than those from normal CD34(+) cells. Remarkably, the copy number of miR-7977 in bone marrow interstitial fluid was elevated not only in acute myeloid leukemia, but also in myelodysplastic syndrome, as compared with lymphoma without bone marrow localization. The transfection of the miR-7977 mimic reduced the expression of the posttranscriptional regulator, poly(rC) binding protein 1, in mesenchymal stem cells. Moreover, the miR-7977 mimic induced aberrant reduction of hematopoietic growth factors in mesenchymal stem cells, resulting in decreased hematopoietic-supporting capacity of bone marrow CD34(+) cells. Furthermore, the reduction of hematopoietic growth factors including Jagged-1, stem cell factor and angiopoietin-1 were reverted by target protection of poly(rC) binding protein 1, suggesting that poly(rC) binding protein 1 could be involved in the stabilization of several growth factors. Thus, miR-7977 in extracellular vesicles may be a critical factor that induces failure of normal hematopoiesis via poly(rC) binding protein 1 suppression.

DOI PubMed

Narrow-Band Ultraviolet B Phototherapy Ameliorates Acute Graft-Versus-Host Disease of the Intestine by Expansion of Regulatory T Cells.

Hashimoto A, Sato T, Iyama S, Yoshida M, Ibata S, Tatekoshi A, Kamihara Y, Horiguchi H, Murase K, Kawano Y, Takada K, Miyanishi K, Kobune M, Ichimiya S, Kato J

PloS one ( Public Library of Science (PLoS) ) 11 ( 3 ) e0152823 - e0152823 2016.03 [Refereed]

DOI PubMed

RNAi-mediated gene silencing of ST6GalNAc I suppresses the metastatic potential in gastric cancer cells

Fumito Tamura, Yasushi Sato, Masahiro Hirakawa, Makoto Yoshida, Michihiro Ono, Takahiro Osuga, Yutaka Okagawa, Naoki Uemura, Yohei Arihara, Kazuyuki Murase, Yutaka Kawano, Satoshi Iyama, Kohichi Takada, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Masayoshi Kobune, Rishu Takimoto, Junji Kato

GASTRIC CANCER ( SPRINGER ) 19 ( 1 ) 85 - 97 2016.01 [Refereed]

ST6GalNAc I is a sialyltransferase controlling the expression of sialyl-Tn antigen (STn), which is overexpressed in several epithelial cancers, including gastric cancer, and is highly correlated with cancer metastasis. However, the functional contribution of ST6GalNAc I to development or progression of gastric cancer remains unclear. In this study, we investigated the effects of suppression of ST6GalNAc I on gastric cancer in vitro and in vivo. Gastric cancer cell lines were transfected with ST6GalNAc I siRNA and were examined by cell proliferation, migration, and invasion assays. We also evaluated the effect of ST6GalNAc I siRNA treatment in a peritoneal dissemination mouse model. The differences in mRNA levels of selected signaling molecules were analyzed by polymerase chain reaction (PCR) arrays associated with tumor metastasis in MKN45 cells. The signal transducer and activator of transcription 5b (STAT5b) signaling pathways that reportedly regulate the insulin-like growth factor-1 (IGF-1) were analyzed by Western blot. ST6GalNAc I siRNA inhibited gastric cancer cell growth, migration, and invasion in vitro. Furthermore, intraperitoneal administration of ST6GalNAc I siRNA- liposome significantly inhibited peritoneal dissemination and prolonged the survival of xenograft model mice with peritoneal dissemination of gastric cancer. PCR array confirmed that suppression of ST6GalNAc I caused a significant reduction in expression of IGF-1 mRNA. Decreased IGF-1 expression in MKN45 cells treated with ST6GalNAc I siRNA was accompanied by reduced phosphorylation of STAT5b. ST6GalNAc I may regulate the gene expression of IGF-1 through STAT5b activation in gastric cancer cells and may be a potential target for treatment of metastasizing gastric cancer.

DOI PubMed

[Neurolymphomatosis of the sciatic nerve diagnosed by FDG-PET/CT].

Usami M, Murase K, Takada K, Iijima K, Yoshida M, Tatekoshi A, Hashimoto A, Iyama S, Sato T, Kobune M, Takimoto R, Kaya M, Yamashita T, Morita R, Hasegawa T, Kato J

[Rinsho ketsueki] The Japanese journal of clinical hematology 57 ( 1 ) 52 - 55 2016.01 [Refereed]

DOI PubMed J-GLOBAL

Erdheim-Chester Disease Involving the Central Nervous System with the Unique Appearance of a Coated Vertebral Artery

Hime Suzuki, Masahiko Wanibuchi, Katsuya Komatsu, Yukinori Akiyama, Takeshi Mikami, Shintaro Sugita, Tadashi Hasegawa, Mitsunori Kaya, Kohichi Takada, Nobuhiro Mikuni

NMC Case Report Journal ( Japan Neurosurgical Society ) 3 ( 4 ) 125 - 128 2016 [Refereed] [Domestic journal]

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. It is characterized by multiple xanthogranulomatous masses throughout the body, predominantly in the tibia. One of the characteristic radiological findings of the lesions associated with ECD is a "coated artery," which is often observed in the aorta. Although approximately one-fourth of ECD cases involve the central nervous system (CNS), an intracranial-coated artery has only been reported in four cases. We report a case of ECD that involves the CNS and has the unique appearance of a coated vertebral artery (VA). These tumors entirely encase the bilateral VAs without stenosis and are attached to the dura. Cranial magnetic resonance imaging also showed multiple extra-axial tumors in the cavernous sinus, the frontal convexity, and the orbital cavity. Further investigation revealed additional extracranial lesions around the cervical carotid artery, at the bilateral tibia, and at the elbow joint. A biopsy of the cervical and tibial lesions confirmed ECD. Steroid therapy resulted in a month-long improvement of preoperative symptoms. However, the patient's condition gradually progressed and he died of pneumonia 1 year after ECD diagnosis. The encasement of the intracranial artery by the tumor without stenosis and the dural attachment suggest ECD, which requires whole body investigation.

DOI PubMed

集学的治療により救命し得たClostridium perfringens感染症による肝膿瘍の2例

久保智洋, 宮西浩嗣, 河野豊, 桜田晃, 石川和真, 佐藤昌則, 保木寿文, 高田弘一, 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 ) 56 ( Suppl.3 ) A1063 - A1063 2015.11 [Refereed]

Effect of duloxetine in Japanese patients with chemotherapy-induced peripheral neuropathy: a pilot randomized trial

Yasuo Hirayama, Kunihiko Ishitani, Yasushi Sato, Satoshi Iyama, Kohichi Takada, Kazuyuki Murase, Hiroyuki Kuroda, Yasuhiro Nagamachi, Yuichi Konuma, Akihito Fujimi, Tamotsu Sagawa, Kaoru Ono, Hiroto Horiguchi, Takeshi Terui, Kazuhiko Koike, Toshiro Kusakabe, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Junji Kato

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY ( SPRINGER JAPAN KK ) 20 ( 5 ) 866 - 871 2015.10 [Refereed]

Chemotherapy-induced peripheral neuropathy (CIPN) is difficult to manage. A phase III trial conducted in the United States demonstrated that duloxetine was effective for CIPN caused by taxane and platinum-based chemotherapy. No randomized trial of duloxetine for CIPN has been conducted in Japan. In this open-label, randomized, crossover study, eligible patients were randomized to Group A or Group B. Group A received duloxetine 20 mg/day orally for the first week and 40 mg/day for the next 3 weeks. Group B received vitamin B12 (VB12) 1.5 mg/day orally for 4 weeks. After a 2- to 4-week washout period, treatment was crossed over for another 4 weeks. The severity of numbness and pain was assessed using a visual analog scale (VAS). Thirty-four patients were enrolled. Obvious decreases in the mean VAS scores for numbness and pain were observed for the periods of duloxetine administration. Significant differences were observed between the duloxetine-first (Group A) and the VB12-first (Group B) groups with respect to numbness (p = 0.03) and pain (p = 0.04) at 4 weeks after administration. Fatigue was observed in six of the 34 participants (17.6 %). Our data suggests that duloxetine has a beneficial effect on CIPN caused by oxaliplatin, paclitaxel, vincristine, or bortezomib in Japanese patients.

DOI PubMed

BAK is a predictive and prognostic biomarker for the therapeutic effect of docetaxel treatment in patients with advanced gastric cancer.

Kubo T, Kawano Y, Himuro N, Sugita S, Sato Y, Ishikawa K, Takada K, Murase K, Miyanishi K, Sato T, Takimoto R, Kobune M, Nobuoka T, Hirata K, Takayama T, Mori M, Hasegawa T, Kato J

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association ( Springer Japan ) 19 ( 3 ) 827 - 838 2015.10 [Refereed]

DOI PubMed CiNii

Increased duodenal iron absorption through up-regulation of divalent metal transporter 1 from enhancement of iron regulatory protein 1 activity in patients with nonalcoholic steatohepatitis

Toshifumi Hoki, Koji Miyanishi, Shingo Tanaka, Kohichi Takada, Yutaka Kawano, Akira Sakurada, Masanori Sato, Tomohiro Kubo, Tsutomu Sato, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Junji Kato

HEPATOLOGY ( WILEY-BLACKWELL ) 62 ( 3 ) 751 - 761 2015.09 [Refereed]

Increased hepatic iron accumulation is thought to be involved in the pathogenesis of nonalcoholic steatohepatitis (NASH). Hepatic iron accumulation, as well as oxidative DNA damage, is significantly increased in NASH livers. However, the precise mechanism of iron accumulation in the NASH liver remains unclear. In this study, 40 cases with a diagnosis of NASH (n=25) or simple steatosis (SS; n=15) by liver biopsy were enrolled. An oral iron absorption test (OIAT) was used, in which 100 mg of sodium ferrous citrate was administered to each individual. The OIAT showed that absorption of iron from the gastrointestinal (GI) tract was increased significantly in NASH patients, compared to SS and control subjects. Iron reduction therapy was effective in patients with NASH, who exhibited iron deposition in the liver and no alanine aminotransferase improvement after other therapies (n=9). Serum hepcidin concentration and messenger RNA (mRNA) levels of divalent metal transporter 1 (DMT1) also were significantly elevated in patients with NASH. OIAT results were correlated with grade of liver iron accumulation and DMT1 mRNA levels. Then, we demonstrated that DMT1 mRNA levels increased significantly in Caco-2/TC7 cell monolayers cultured in transwells with serum from NASH patients. An electrophoresis mobility shift assay showed activation of iron regulatory protein (IRP) in those cells, and IRP1 small interfering RNA clearly inhibited the increase of DMT1 mRNA levels. Conclusion: In spite of elevation of serum hepcidin, iron absorption from the GI tract increased through up-regulation of DMT1 by IRP1 activation by humoral factor(s) in sera of patients with NASH. (Hepatology 2015) Hepatology 2015;62:751-761)

DOI PubMed

A long-term survival case of hepatic epithelioid hemangioendothelioma with lung metastases treated with recombinant interleukin-2

Toshifumi Hoki, Koji Miyanishi, Yutaka Kawano, Shota Yamada, Kohei Harada, Masahiro Hirakawa, Fumito Tamura, Kazuma Ishikawa, Kohichi Takada, Tsutomu Sato, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Tadashi Hasegawa, Junji Kato

Acta Hepatologica Japonica ( Japan Society of Hepatology ) 56 ( 7 ) 356 - 365 2015.07 [Refereed]

A 37-year-old woman was found in a medical checkup to have liver dysfunction. Abdominal CT scan im-ages demonstrated multiple liver tumors. She was referred to our hospital for examination and treatment. Ab-dominal enhanced CT scan images showed irregularly spreading hypovascular tumors located in the surface of both hepatic lobes. Needle liver biopsy revealed many atypical cells with positive staining for factor VIII-related-antigen and CD34. The tumor was diagnosed as an hepatic epithelioid hemangioendothelioma (HEHE). She has received intravenous administration of recombinant interleukin-2 (rIL-2) for six years with a reduction in tumor volume. HEHE is a rare tumor which has low malignant potential, also is often unresectable due to multifocal tumors involving both hepatic lobes at the time of diagnosis. There was no generally accepted therapy except surgical resection and liver transplantation. The long-term survival observed in the present case may indicate the effectiveness of rIL-2 for HEHE.

DOI

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Papers - TAKADA Kouichi