Faculty Profiles - ISHITSUKA Kenji

Papers - ISHITSUKA Kenji

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Arai A, Yoshimitsu M, Otsuka M, Ito Y, Miyazono T, Nakano N, Obama K, Nakashima H, Hanada S, Owatari S, Nakamura D, Tokunaga M, Kamada Y, Utsunomiya A, Haraguchi K, Hayashida M, Fujino S, Odawara J, Tabuchi T, Suzuki S, Hamada H, Kawamoto Y, Uchida Y, Hachiman M, Ishitsuka K. . Identification of putative noncanonical driver mutations in patients with essential thrombocythemia . Eur J Haematol.110 ( 6 ) 639 - 647 2023.6Identification of putative noncanonical driver mutations in patients with essential thrombocythemiaReviewed

Hosono N, Chi S, Yamauchi T, Fukushima K, Shibayama H, Katagiri S, Gotoh A, Eguchi M, Morishita T, Ogasawara R, Kondo T, Yanada M, Yamamoto K, Kobayashi T, Kuroda J, Usuki K, Utsu Y, Yoshimitsu M, Ishitsuka K, Ono T, Takahashi N, Iyama S, Kojima K, Nakamura Y, Fukuhara S, Izutsu K, Abutani H, Yamauchi N, Yuda J, Minami Y; All HM-SCREEN-Japan 01 Investigators. . Clinical utility of genomic profiling of AML using paraffin-embedded bone marrow clots: HM-SCREEN-Japan 01 . Cancer Sci. 114 ( 5 ) 2098 - 2108 2023.5Clinical utility of genomic profiling of AML using paraffin-embedded bone marrow clots: HM-SCREEN-Japan 01Reviewed

Kenji Ishitsuka . T cell lymphoma: time to make discoveries and advance treatment . Int J Hematol . 117 ( 4 ) 473 - 474 2023.4T cell lymphoma: time to make discoveries and advance treatmentInvited Reviewed

Hiramatsu H, Nosaka K, Kusumoto S, Nakano N, Choi I, Yoshimitsu M, Imaizumi Y, Hidaka M, Sasaki H, Makiyama J, Ohtsuka E, Jo T, Ogata M, Ito A, Yonekura K, Tatetsu H, Kato T, Kawakita T, Suehiro Y, Ishitsuka K, Iida S, Matsutani T, Nishikawa H, Utsunomiya A, Ueda R, Ishida T. . Landscape of immunoglobulin heavy chain γ gene class switch recombination in patients with adult T-cell leukemia-lymphoma. . Haematologica.108 ( 4 ) 1173 - 1178 2023.4Landscape of immunoglobulin heavy chain γ gene class switch recombination in patients with adult T-cell leukemia-lymphoma.Reviewed

Tokunaga M, Nakano N, Fuji S, Wake A, Utsunomiya A, Ito A, Eto T, Kawakita T, Mori Y, Moriuchi Y, Suehiro Y, Miyazaki Y, Uchida N, Sawayama Y, Ishitsuka K, Kanda J, Kimura T, Ichinohe T, Atsuta Y, Fukuda T, Yoshimitsu M, Kato K. . Cord blood is a suitable donor source of allogeneic hematopoietic cell transplantation for adult T-cell leukemia-lymphoma: a nationwide retrospective study. . Bone Marrow Transplant. 58 ( 4 ) 462 - 464 2023.4Cord blood is a suitable donor source of allogeneic hematopoietic cell transplantation for adult T-cell leukemia-lymphoma: a nationwide retrospective study.Reviewed

Owatari S, Tokunaga M, Nakamura D, Uozumi K, Sagara Y, Nakamura H, Haraguchi K, Nakano N, Yoshimitsu M, Ito Y, Utsunomiya A, Otsuka M, Hanada S, Iwanaga M, Ishitsuka K. . A decrease in newly diagnosed patients with adult T-cell leukemia/lymphoma in Kagoshima, a highly endemic area of HTLV-1 in southwestern Japan . Leuk Lymphoma.64 ( 4 ) 865 - 873 2023.4A decrease in newly diagnosed patients with adult T-cell leukemia/lymphoma in Kagoshima, a highly endemic area of HTLV-1 in southwestern JapanReviewed

Kenji Ishitsuka . Prognostic indices for peripheral T-cell lymphoma - not otherwise specified and adult T-cell leukemia/lymphoma: From past to future . J Clin Exp Hematop .63 ( 1 ) 1 - 11 2023.3Prognostic indices for peripheral T-cell lymphoma - not otherwise specified and adult T-cell leukemia/lymphoma: From past to futureReviewed

Izutsu K, Makita S, Nosaka K, Yoshimitsu M, Utsunomiya A, Kusumoto S, Morishima S, Tsukasaki K, Kawamata T, Ono T, Rai S, Katsuya H, Ishikawa J, Yamada H, Kato K, Tachibana M, Kakurai Y, Adachi N, Tobinai K, Yonekura K, Ishitsuka K. . An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma. . Blood.141 ( 10 ) 1159 - 1168 2023.3An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma.Reviewed

Rai S, Kim WS, Ando K, Choi I, Izutsu K, Tsukamoto N, Yokoyama M, Tsukasaki K, Kuroda J, Ando J, Hidaka M, Koh Y, Shibayama H, Uchida T, Yang DH, Ishitsuka K, Ishizawa K, Kim JS, Lee HG, Minami H, Eom HS, Kurosawa M, Lee JH, Lee JS, Lee WS, Nagai H, Shindo T, Yoon DH, Yoshida S, Gillings M, Onogi H, Tobinai K. . Oral HDAC inhibitor tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: phase IIb results. . Haematologica. 108 ( 3 ) 811 - 821 2023.3Oral HDAC inhibitor tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: phase IIb results.Reviewed

小代彩, 太崎友紀子, 内田那津子, 濱田朋紀, 赤星里佳, 上野卓也, 田淵智久, 有馬直佑, 林田真衣子, 新居亮彦, 中村大輔, 吉満誠, 小林裕明, 石塚賢治 . チロシンキナーゼ阻害薬中断後の分子遺伝学的再燃に対してインターフェロンαを投与し出産し得た慢性骨髄性白血病 . 臨床血液64 ( 2 ) 102 - 106 2023.2 チロシンキナーゼ阻害薬中断後の分子遺伝学的再燃に対してインターフェロンαを投与し出産し得た慢性骨髄性白血病Reviewed

Imaizumi Y, Iwanaga M, Nosaka K, Ishitsuka K, Ishizawa K, Ito S, Amano M, Ishida T, Uike N, Utsunomiya A, Ohshima K, Tanaka J, Tokura Y, Tobinai K, Watanabe T, Uchimaru K, Tsukasaki K. . Validation of the iATL-PI prognostic index in therapeutic decision-making for patients with smoldering and chronic ATL: a multicenter study . Int J Hematol. 117 ( 2 ) 206 - 215 2023.2Validation of the iATL-PI prognostic index in therapeutic decision-making for patients with smoldering and chronic ATL: a multicenter studyReviewed

Mori Y, Uchida N, Harada T, Katayama Y, Wake A, Iwasaki H, Eto T, Morishige S, Fujisaki T, Ito Y, Kamimura T, Takahashi T, Imamura Y, Tanimoto K, Ishitsuka K, Sugita J, Kawano N, Tanimoto K, Yoshimoto G, Choi I, Hidaka T, Ogawa R, Takamatsu Y, Miyamoto T, Akashi K, Nagafuji K. . Predictors of impaired antibody response after SARS-CoV-2 mRNA vaccination in hematopoietic cell transplant recipients: A Japanese multicenter observational study. . Am J Hematol. 98 ( 1 ) 102 - 111 2023.1Predictors of impaired antibody response after SARS-CoV-2 mRNA vaccination in hematopoietic cell transplant recipients: A Japanese multicenter observational study.Reviewed

石塚賢治 . 医学と医療の最前線　成人T細胞白血病・リンパ腫の診療 . 日本内科学会雑誌112 ( 1 ) 89 - 93 2023.1医学と医療の最前線　成人T細胞白血病・リンパ腫の診療Invited Reviewed

Suzuki S, Hourai S, Uozumi K, Uchida Y, Yoshimitsu M, Miho H, Arima N, Ueno SI, Ishitsuka K. . Gamma-secretase inhibitor does not induce cytotoxicity in adult T-cell leukemia cell lines despite NOTCH1 expression. . BMC Cancer. 22 ( 1 ) 1065 2022.10Gamma-secretase inhibitor does not induce cytotoxicity in adult T-cell leukemia cell lines despite NOTCH1 expression.Reviewed

Kamada Y, Arima N, Hayashida M, Nakamura D, Yoshimitsu M, Ishitsuka K. . Prediction of the risk for graft versus host disease after allogeneic hematopoietic stem cell transplantation in patients treated with mogamulizumab . Leuk Lymphoma. 63 ( 7 ) 1701 - 2707 2022.7Prediction of the risk for graft versus host disease after allogeneic hematopoietic stem cell transplantation in patients treated with mogamulizumabReviewed

Kozako T, Kato N, Ohsugi T, Uchida YI, Yoshimitsu M, Ishitsuka K, Higaki Y, Sato H, Aikawa A, Honda SI. . SRT1720 induces SIRT1-independent cell death in adult T-cell leukemia/lymphoma. . FEBS J. 289 ( 12 ) 3477 - 3488 2022.6SRT1720 induces SIRT1-independent cell death in adult T-cell leukemia/lymphoma.Reviewed

Kawahira M, Kanmura S, Mizuno K, Machida K, Ohtsuka T, Sato M, Enokida H, Yamashita M, Kanekura T, Arima S, Nakamura N, Sugiura T, Yoshimoto K, Kobayashi H, Ishitsuka K, Suzuki S, Ueno S, Ido A. . Effects of immune checkpoint inhibitor therapy resumption in patients with malignant tumors after moderate-to-severe immune-related adverse events . PLoS One. 17 ( 4 ) e0267572 2022.4Effects of immune checkpoint inhibitor therapy resumption in patients with malignant tumors after moderate-to-severe immune-related adverse eventsReviewed

Yoshimitsu M, Tofuku K, Ikeda D, Ohno N, Ishitsuka K, Nakashima H. . Cardiac Involvement of Adult T Cell Leukemia/Lymphoma. . Intern Med. 61 ( 7 ) 1055 - 1057 2022.4Cardiac Involvement of Adult T Cell Leukemia/Lymphoma.Reviewed

石塚賢治 . 悪性リンパ腫アップデート . 日本内科学会雑誌111 ( 3 ) 566 - 571 2022.3悪性リンパ腫アップデートInvited Reviewed

Kogure Y, Kameda T, Koya J, Yoshimitsu M, Nosaka K, Yasunaga JI, Imaizumi Y, Watanabe M, Saito Y, Ito Y, McClure MB, Tabata M, Shingaki S, Yoshifuji K, Chiba K, Okada A, Kakiuchi N, Nannya Y, Kamiunten A, Tahira Y, Akizuki K, Sekine M, Shide K, Hidaka T, Kubuki Y, Kitanaka A, Hidaka M, Nakano N, Utsunomiya A, Sica RA, Acuna-Villaorduna A, Janakiram M, Shah U, Ramos JC, Shibata T, Takeuchi K, Takaori-Kondo A, Miyazaki Y, Matsuoka M, Ishitsuka K, Shiraishi Y, Miyano S, Ogawa S, Ye BH, Shimoda K, Kataoka K. . Whole-genome landscape of adult T-cell leukemia/lymphoma. . Blood139 ( 7 ) 967 - 982 2022.2Whole-genome landscape of adult T-cell leukemia/lymphoma.Reviewed International coauthorship

Utsunomiya A, Tokunaga M, Nakano N, Fujiwara H, Miyamoto T, Ogata M, Miyazaki Y, Ishitsuka K, Sakaida E, Taji H, Wakayama T, Ichinohe T, Fukuda T, Atsuta Y, Kato K, Yoshimitsu M. . Long-term follow-up of patients with ATL after autologous stem cell transplantation. . Bone Marrow Transplant.57 ( 2 ) 323 - 325 2022.2Long-term follow-up of patients with ATL after autologous stem cell transplantation.Reviewed

Nosaka K, Kusumoto S, Nakano N, Choi I, Yoshimitsu M, Imaizumi Y, Hidaka M, Sasaki H, Makiyama J, Ohtsuka E, Jo T, Ogata M, Ito A, Yonekura K, Tatetsu H, Kato T, Kawakita T, Suehiro Y, Ishitsuka K, Iida S, Matsutani T, Utsunomiya A, Ueda R, Ishida T. . Clinical significance of the immunoglobulin G heavy-chain repertoire in peripheral blood mononuclear cells of adult T-cell leukaemia-lymphoma patients receiving mogamulizumab. . Br J Haematol.196 ( 3 ) 629 - 638 2022.2Clinical significance of the immunoglobulin G heavy-chain repertoire in peripheral blood mononuclear cells of adult T-cell leukaemia-lymphoma patients receiving mogamulizumab.Reviewed

Nakano D, Ishitsuka K, Ishihara M, Tsuchihashi R, Okawa M, Tamura K, Kinjo J. . Screening of Promising Chemotherapeutic Candidates from Plants against Human Adult T-Cell Leukemia/Lymphoma (VII): Active Principles from Thuja occidentalis L . Molecules25 ( 24 ) 7619 2021.12Screening of Promising Chemotherapeutic Candidates from Plants against Human Adult T-Cell Leukemia/Lymphoma (VII): Active Principles from Thuja occidentalis LReviewed

Ito S, Iwanaga M, Nosaka K, Imaizumi Y, Ishitsuka K, Amano M, Utsunomiya A, Tokura Y, Watanabe T, Uchimaru K, Tsukasaki K; Collaborative Investigators. . Epidemiology of adult T-cell leukemia-lymphoma in Japan: An updated analysis, 2012-2013. . Cancer Sci. 112 ( 10 ) 4346 - 4354 2021.10Epidemiology of adult T-cell leukemia-lymphoma in Japan: An updated analysis, 2012-2013.Reviewed

Ishitsuka K. . Diagnosis and management of adult T-cell leukemia/lymphoma . Seminars in Hematology58 ( 2 ) 114 - 122 2021.4

Uchida Y. . RLTPR Q575E: A novel recurrent gain-of-function mutation in patients with adult T-cell leukemia/lymphoma . European Journal of Haematology106 ( 2 ) 221 - 229 2021.2

Imaizumi Y. . Prognosis of patients with adult T-cell leukemia/lymphoma in Japan: A nationwide hospital-based study . Cancer Science111 ( 12 ) 4567 - 4580 2020.12

Yonekura K. . Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study . Blood Advances4 ( 20 ) 5133 - 5154 2020.10

Nakano Daisuke, Ishitsuka Kenji, Takashima Maya, Arima Rie, Satou Aya, Tsuchihashi Ryota, Okawa Masafumi, Tamura Kazuo, Kinjo Junei . Screening of Promising Chemotherapeutic Candidates from Plants against Human Adult T-Cell Leukemia/Lymphoma(VI): Cardenolides from Asclepias curassavica(和訳中) . Biological & Pharmaceutical Bulletin43 ( 10 ) 1609 - 1614 2020.10Screening of Promising Chemotherapeutic Candidates from Plants against Human Adult T-Cell Leukemia/Lymphoma(VI): Cardenolides from Asclepias curassavica(和訳中)

Aikawa A. . Cell death induced by dorsomorphin in adult T-cell leukemia/lymphoma is AMPK-independent . FEBS Journal287 ( 18 ) 4005 - 4015 2020.9

Okuma K. . Establishment of a novel diagnostic test algorithm for human T-cell leukemia virus type 1 infection with line immunoassay replacement of western blotting: A collaborative study for performance evaluation of diagnostic assays in Japan . Retrovirology17 ( 1 ) 26 2020.8

Kobata K, Kimura S, Mihashi Y, Iwasaki H, Nonaka S, Matsumoto S, Takamatsu Y, Choi I, Kawauchi S, Ishitsuka K, Takeshita M. . Clinical and cytopathological characteristics of HTLV-1+ hodgkin lymphoma. . Cancer Med.9 ( 16 ) 5788 - 5797 2020.8Clinical and cytopathological characteristics of HTLV-1+ hodgkin lymphoma.Reviewed

Arimura A, Fujii K, Uchida Y, Higashi Y, Arima N, Yoshimitsu M, Ishitsuka K, Kanekura T. . Septic vasculitis induces cutaneous involvement of adult T-cell leukemia/lymphoma. . Int J Dermatol. 59 ( 8 ) e298 - e300 2020.8Septic vasculitis induces cutaneous involvement of adult T-cell leukemia/lymphoma.Reviewed

Yokota R. . Novel anti-CD70 antibody drug conjugate for the treatment of adult T-cell leukemia (ATL) . Anticancer Research40 ( 8 ) 4471 - 4479 2020.8

小代彩, 井上大栄, 鎌田勇平, 藤野聡司, 田淵智久, 有馬直佑, 内田友一朗, 八幡美保, 中村大輔, 吉満誠, 石塚賢治 . Mogamulizumabが奏効した著明な肝障害と胸腹水を伴う成人T細胞白血病・リンパ腫 . 臨床血液61 ( 6 ) 612 - 616 2020.6Mogamulizumabが奏効した著明な肝障害と胸腹水を伴う成人T細胞白血病・リンパ腫

Publisher：(一社)日本血液学会-東京事務局

成人T細胞白血病・リンパ腫(ATL)はヒトTリンパ球向性ウイルスI型が原因となり発症する予後不良な末梢性T細胞腫瘍である。腫瘍浸潤による肝障害のため殺細胞性抗がん剤による化学療法が困難な状況をmogamulizumab(Moga)で救援し,長期寛解が得られている急性型ATLを報告する。症例は66歳男性,ATLの肝浸潤に伴う全身状態悪化のため減量化学療法を開始したが効果に乏しく,高ビリルビン血症,低アルブミン血症のため継続困難であった。Moga投与後,末梢血異常リンパ球は急速に減少,肝障害は改善し,通常量の化学療法が施行可能となった。抗体薬のMogaは体内薬物動態への肝代謝能や血清アルブミン値の影響が少ないと考えられ,肝浸潤による高ビリルビン血症や低アルブミン血症のため通常の殺細胞性抗がん剤を投与しにくい状態のATL患者の救援治療としても有望な選択肢である。(著者抄録)

Nakamura D. . Treatment of aggressive adult T-cell leukemia/lymphoma: a retrospective study in a hospital located in HTLV-1 highly endemic area . International Journal of Hematology111 ( 2 ) 234 - 240 2020.2

Nakamura D, Yoshimitsu M, Tabuchi T, Arima N, Hayashida M, Inoue H, Matsushita K, Matsumoto T, Arima N, Ishitsuka K. . Treatment of aggressive adult T-cell leukemia/lymphoma: a retrospective study in a hospital located in HTLV-1 highly endemic area. . Int J Hematol. 111 ( 2 ) 234 - 240 2020.2Treatment of aggressive adult T-cell leukemia/lymphoma: a retrospective study in a hospital located in HTLV-1 highly endemic area.Reviewed

Nakamura Daisuke, Yoshimitsu Makoto, Tabuchi Tomohisa, Arima Naosuke, Hayashida Maiko, Inoue Hirosaka, Matsushita Kakushi, Matsumoto Tadashi, Arima Naomichi, Ishitsuka Kenji . アグレッシブ成人T細胞白血病/リンパ腫の治療　HTLV-1高蔓延地域の病院で実施した後ろ向き研究(Treatment of aggressive adult T-cell leukemia/lymphoma: a retrospective study in a hospital located in HTLV-1 highly endemic area) . International Journal of Hematology111 ( 2 ) 234 - 240 2020.2アグレッシブ成人T細胞白血病/リンパ腫の治療　HTLV-1高蔓延地域の病院で実施した後ろ向き研究(Treatment of aggressive adult T-cell leukemia/lymphoma: a retrospective study in a hospital located in HTLV-1 highly endemic area)

Publisher：(一社)日本血液学会

ヒトT細胞白血病ウイルスI型(HTLV-1)蔓延地域である鹿児島に位置する一病院において、2005〜2014年に急性型、リンパ腫型、予後不良因子を有する慢性型のアグレッシブ成人T細胞白血病/リンパ腫(ATL)と診断された患者191例(男性105例、女性86例、年齢中央値72歳)の治療について後ろ向きに分析した。138例がOPEC/MPEC、33例がVCAP-AMP-VECPで治療された。2010年頃まではOPEC/MPECが主に使用されていたが、徐々にVCAP-AMP-VECPに切り替えられ、特に若年患者に対する使用が増えた。VCAP-AMP-VECPで治療された患者の2年全生存率は、70歳未満の患者ではOPEC/MPECよりも有意に高かったが、70歳以上の患者では有意差は示されなかった。これらの結果から、OPEC/MPECによる治療は、高齢者であっても治療強度を低下させずに行うことができ、VCAP-AMP-VECPと比較して劣っておらず、高齢のアグレッシブATL患者の代替療法の一つの選択肢となる可能性が示された。

3. Nakano D, Ishitsuka K, Takashima M, Arima R, Satou A, Tsuchihashi R, Okawa M, Tamura K, Kinjo J. . Screening of Promising Chemotherapeutic Candidates from Plants against Human Adult T-Cell Leukemia/Lymphoma (VI): Cardenolides from Asclepias curassavica. . Biol Pharm Bull.63 ( 10 ) 1609 - 1614 2020Screening of Promising Chemotherapeutic Candidates from Plants against Human Adult T-Cell Leukemia/Lymphoma (VI): Cardenolides from Asclepias curassavica.Reviewed

SHODAI Aya, YOSHIMITSU Makoto, ISHITSUKA Kenji, INOUE Hirosaka, KAMADA Yuhei, FUJINO Satoshi, TABUCHI Tomohisa, ARIMA Naosuke, UCHIDA Yuichiro, HACHIMAN Miho, NAKAMURA Daisuke . Adult T-cell leukemia-lymphoma with severe hepatic damage and fluid retention successfully treated with mogamulizumab . Rinsho Ketsueki61 ( 6 ) 612 - 616 2020

Publisher：The Japanese Society of Hematology

Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell malignancy caused by the human T-cell lymphotropic virus, type I and it has an extremely poor prognosis. A 66-year-old man with severe hepatic damage, massive pleural effusion and ATL cell infiltration-induced ascites was referred to our department. Reduced-intensity cytotoxic chemotherapy was attempted, but could not continue due to persistent hyperbilirubinemia. Laboratory results also showed elevated lactate dehydrogenase (LDH) and serum albumin levels were profoundly decreased. A humanized monoclonal antibody against chemokine receptor type 4 (CCR4), mogamulizumab (Moga), was thereby challenged and it successfully resolved the hepatic damage. Finally, a standard dose of chemotherapy could be administered, and it induced a complete remission. The patient is still in remission more than three years after the final dosage of standard chemotherapy. These results indicate that Moga, whose pharmacokinetics are not significantly influenced by hepatic function or serum albumin, could be a promising treatment option for patients with ATL complicated by severe hepatic damage due to infiltration of ATL cells.

DOI： 10.11406/rinketsu.61.612

PubMed

Nakano Daisuke, Ishitsuka Kenji, Takashima Maya, Arima Rie, Satou Aya, Tsuchihashi Ryota, Okawa Masafumi, Tamura Kazuo, Kinjo Junei . Screening of Promising Chemotherapeutic Candidates from Plants against Human Adult T-Cell Leukemia/Lymphoma (Ⅵ) : Cardenolides from Asclepias curassavica . Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ43 ( 10 ) 1609 - 1614 2020

Publisher：公益社団法人日本薬学会

In the course of our screening program for novel chemotherapeutic candidates from plants against adult T-cell leukemia/lymphoma, the extracts of Asclepias curassavica L. showed potent activity against MT-1 and MT-2 cells. Therefore, we attempted to isolate their active components. We identified a new cardenolide, 19-dihydrocalactinic acid methyl ester (1), along with 16 known cardenolides (2–17). Their structures were determined on the basis of spectroscopic data. Almost all of the isolated cardenolides inhibited the growth of both tumor cell lines. All the doubly linked cardenolides (11–17) except for 14 showed more potent activity than the other cardenolides. A comparison of the activities of 11, 14 and 16 revealed that the presence of hydroxy or acetoxy functional groups at C-16 led to a decrease in the activity. The 50% effective concentration (EC50) value of calotropin (11) against MT-2 cells was comparable to the potency of the clinical antineoplastic drug doxorubicin. The cytotoxic effect of 11 toward normal mononuclear cells obtained from the peripheral blood (PB-MNCs) was observed at a concentration 6 to 12 times higher than that used to induce growth inhibition against MT-1 and MT-2 cells. The proportions of annexin V-positive cells after 72 h of treatment with 11 were increased, indicating that it significantly induced apoptosis in MT-1 and MT-2 cells in a concentration-dependent manner. Cell cycle experiments demonstrated that 11 arrested MT-1 and MT-2 cells at the G2/M phase. Therefore, compound 11 may be a promising candidate for the treatment of adult T-cell leukemia/lymphoma.

DOI： 10.1248/bpb.b20-00465

Scopus

PubMed

Kozako T. . High expression of NAMPT in adult T-cell leukemia/lymphoma and anti-tumor activity of a NAMPT inhibitor . European Journal of Pharmacology865 172738 2019.12

Yoshimitsu M. . Essential thrombocytosis attributed to JAK2-T875N germline mutation . International Journal of Hematology110 ( 5 ) 584 - 590 2019.11

Yoshimitsu M, Hachiman M, Uchida Y, Arima N, Arai A, Kamada Y, Shide K, Ito M, Shimoda K, Ishitsuka K. . Essential thrombocytosis attributed to JAK2-T875N germline mutation. . Int J Hematol.110 ( 5 ) 584 - 590 2019.11Essential thrombocytosis attributed to JAK2-T875N germline mutation.Reviewed

Uchida Y, Okubo A, Hayashida M, Inoue H, Tamura H, Fujii K, Ishitsuka K, Kanekura T. . Type D lymphomatoid papulosis associated with chemotherapy/chemoradiotherapy-induced severe chronic lymphocytopenia. . J Dermatol.46 ( 11 ) e412 - e414 2019.11Type D lymphomatoid papulosis associated with chemotherapy/chemoradiotherapy-induced severe chronic lymphocytopenia.Reviewed

Yoshimitsu Makoto, Hachiman Miho, Uchida Yuichiro, Arima Naosuke, Arai Akihiko, Kamada Yuhei, Shide Kotaro, Ito Masafumi, Shimoda Kazuya, Ishitsuka Kenji . JAK2-T875N生殖細胞系列変異に起因する本態性血小板増加症(Essential thrombocytosis attributed to JAK2-T875N germline mutation) . International Journal of Hematology110 ( 5 ) 584 - 590 2019.11JAK2-T875N生殖細胞系列変異に起因する本態性血小板増加症(Essential thrombocytosis attributed to JAK2-T875N germline mutation)

Publisher：(一社)日本血液学会

症例は46歳女性で、18年間にわたり血小板増加が続いており、本態性血小板増加症(ET)と診断された。末梢血単球のゲノムDNAを用いたエクソーム解析で、エクソン18におけるヌクレオチド2623でのJAK2 C-to-A変異c2623aによってposition 875におけるトレオニンからアスパラギンへのアミノ酸置換がもたらされたことが明らかになった。変異は頬側スワブ由来ゲノムDNAとCD3陽性リンパ球由来ゲノムDNAを用いた標的配列決定によって確認した。父親に血小板増加症と脳卒中の病歴があった。JAK2活性と細胞外シグナル制御キナーゼ(Erk)およびシグナル伝達性転写因子(STAT)といった下流シグナル伝達に対する変異機能を、JAK2-T875N遺伝子導入または形質導入細胞株を用いて評価した。V617FまたはT875N変異を有するJAK2相補DNAを遺伝子導入した293T細胞により、リン酸化JAK2およびErkの増加が示された。プロモーターアッセイによってSTAT3およびSTAT5活性の強化を確認した。JAK2-T875N遺伝子導入Ba/F3細胞では、インターロイキン-3刺激なしで細胞増殖の亢進が認められた。

Yoshimitsu M. . A retrospective analysis of haplo-identical HLA-mismatch hematopoietic transplantation without posttransplantation cyclophosphamide for GVHD prophylaxis in patients with adult T-cell leukemia–lymphoma . Bone Marrow Transplantation54 ( 8 ) 1266 - 1274 2019.8

Toyoda K, Tsukasaki K, Machida R, Kadota T, Fukushima T, Ishitsuka K, Maruyama D, Nagai H. . Possibility of a risk-adapted treatment strategy for untreated aggressive adult T-cell leukaemia-lymphoma (ATL) based on the ATL prognostic index: a supplementary analysis of the JCOG9801. . Br J Haematol.187 ( 3 ) 440 - 447 2019.8Possibility of a risk-adapted treatment strategy for untreated aggressive adult T-cell leukaemia-lymphoma (ATL) based on the ATL prognostic index: a supplementary analysis of the JCOG9801.Reviewed

Toyoda K. . Possibility of a risk-adapted treatment strategy for untreated aggressive adult T-cell leukaemia-lymphoma (ATL) based on the ATL prognostic index: a supplementary analysis of the JCOG9801 . British Journal of Haematology186 ( 3 ) 440 - 447 2019.8

Suzuki S. . A survivin-responsive, conditionally replicating adenovirus induces potent cytocidal effects in adult T-cell leukemia/lymphoma . BMC Cancer19 ( 1 ) 516 2019.5

Ishitsuka K, Yurimoto S, Tsuji Y, Iwabuchi M, Takahashi T, Tobinai K. . Safety and effectiveness of mogamulizumab in relapsed or refractory adult T-cell leukemia-lymphoma. . Eur J Haematol. 102 ( 5 ) 407 - 415 2019.5Safety and effectiveness of mogamulizumab in relapsed or refractory adult T-cell leukemia-lymphoma.Reviewed

Suzuki S, Kofune H, Uozumi K, Yoshimitsu M, Arima N, Ishitsuka K, Ueno SI, Kosai KI. . A survivin-responsive, conditionally replicating adenovirus induces potent cytocidal effects in adult T-cell leukemia/lymphoma. . BMC Cancer.19 ( 1 ) 516 2019.5A survivin-responsive, conditionally replicating adenovirus induces potent cytocidal effects in adult T-cell leukemia/lymphoma.Reviewed

Ishitsuka K. . Safety and effectiveness of mogamulizumab in relapsed or refractory adult T-cell leukemia-lymphoma . European Journal of Haematology102 ( 5 ) 407 - 415 2019.5

Cook LB, Fuji S, Hermine O, Bazarbachi A, Ramos JC, Ratner L, Horwitz S, Fields P, Tanase A, Bumbea H, Cwynarski K, Taylor G, Waldmann TA, Bittencourt A, Marcais A, Suarez F, Sibon D, Phillips A, Lunning M, Farid R, Imaizumi Y, Choi I, Ishida T, Ishitsuka K, Fukushima T, Uchimaru K, Takaori-Kondo A, Tokura Y, Utsunomiya A, Matsuoka M, Tsukasaki K, Watanabe T. . Revised Adult T-Cell Leukemia-Lymphoma International Consensus Meeting Report. . J Clin Oncol.37 ( 8 ) 677 - 687 2019.3Revised Adult T-Cell Leukemia-Lymphoma International Consensus Meeting Report.Reviewed

Cook L.B. . Revised adult T-cell leukemia-lymphoma international consensus meeting report . Journal of Clinical Oncology37 ( 8 ) 677 - 687 2019.3

Mezawa H. . Prevalence of congenital anomalies in the Japan environment and children’s study . Journal of Epidemiology29 ( 7 ) 247 - 256 2019.1

Hashimoto G. . A case of recurrent transient global amnesia showing different symptom duration and MRI findings . Clinical Neurology59 ( 9 ) 575 - 578 2019

Yoshimitsu M, Utsunomiya A, Fuji S, Fujiwara H, Fukuda T, Ogawa H, Takatsuka Y, Ishitsuka K, Yokota A, Okumura H, Ishii K, Nishikawa A, Eto T, Yonezawa A, Miyashita K, Tsukada J, Tanaka J, Atsuta Y, Kato K; ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation. . A retrospective analysis of haplo-identical HLA-mismatch hematopoietic transplantation without posttransplantation cyclophosphamide for GVHD prophylaxis in patients with adult T-cell leukemia-lymphoma. . Bone Marrow Transplant 2018.12A retrospective analysis of haplo-identical HLA-mismatch hematopoietic transplantation without posttransplantation cyclophosphamide for GVHD prophylaxis in patients with adult T-cell leukemia-lymphoma.Reviewed

Kuramitsu M, Okuma K, Nakashima M, Sato T, Sasaki D, Hasegawa H, Umeki K, Kubota R, Sasada K, Sobata R, Matsumoto C, Kaneko N, Tezuka K, Matsuoka S, Utsunomiya A, Koh KR, Ogata M, Ishitsuka K, Taki M, Nosaka K, Uchimaru K, Iwanaga M, Sagara Y, Yamano Y, Okayama A, Miura K, Satake M, Saito S, Watanabe T, Hamaguchi I. . Development of reference material with assigned value for human T-cell leukemia virus type 1 quantitative PCR in Japan. . Microbiol Immunol.62 ( 10 ) 673 - 676 2018.10Development of reference material with assigned value for human T-cell leukemia virus type 1 quantitative PCR in Japan.Reviewed

Kuramitsu M. . Development of reference material with assigned value for human T-cell leukemia virus type 1 quantitative PCR in Japan . Microbiology and Immunology62 ( 10 ) 673 - 676 2018.10

Kuramitsu Madoka, Okuma Kazu, Nakashima Makoto, Sato Tomoo, Sasaki Daisuke, Hasegawa Hiroo, Umeki Kazumi, Kubota Ryuji, Sasada Keiko, Sobata Rieko, Matsumoto Chieko, Kaneko Noriaki, Tezuka Kenta, Matsuoka Sahoko, Utsunomiya Atae, Koh Ki-Ryang, Ogata Masao, Ishitsuka Kenji, Taki Mai, Nosaka Kisato, Uchimaru Kaoru, Iwanaga Masako, Sagara Yasuko, Yamano Yoshihisa, Okayama Akihiko, Miura Kiyonori, Satake Masahiro, Saito Shigeru, Watanabe Toshiki, Hamaguchi Isao . 日本におけるヒトT細胞白血病ウイルス1型定量的PCRの値を定めた基準試料の開発(Development of reference material with assigned value for human T-cell leukemia virus type 1 quantitative PCR in Japan) . Microbiology and Immunology62 ( 10 ) 673 - 676 2018.10日本におけるヒトT細胞白血病ウイルス1型定量的PCRの値を定めた基準試料の開発(Development of reference material with assigned value for human T-cell leukemia virus type 1 quantitative PCR in Japan)

Publisher：John Wiley & Sons Australia, Ltd

ヒトT細胞白血病ウイルス1型(HTLV-1)定量的PCRの標準化を目的として、基準試料を開発したので報告した。Jurkat細胞で希釈したTL-Om1細胞の凍結乾燥細胞基準試料を調製し、HTLV-1定量的PCRに対する一時的基準として品質を評価した。基準試料のプロウイルス量(PVL)に割り当てる数値をデジタルPCRで判定した。HTLV-1定量的PCR標的シーケンスと内部標準遺伝子標的シーケンスを混合したテスト検体を測定して、デジタルPCR結果の精度を確認した。デジタルPCR結果が絶対値に極めて近いことを確認した。基準試料のPVLを2.71copy/100細胞と判定した。九つの協力機関に対して、それぞれの機関の方法を用いて基準試料のPVLの測定を依頼した。結果は1.08〜3.49copy/100細胞で、機関間の最大差が3.23倍となり、幾何平均は2.23copy/100細胞であった。基準試料の付与値を組み込んだ式を用いてこれらのPVLを修正することで矛盾を最小化しなければならなかった。別機関で臨床検体のPVLを測定したところ、修正後にほとんどの臨床検体で研究室間の幾何変動係数が小さかった。基準試料の値を組み入れた式を用いた修正によって、研究室間の差異を最小化できることが示された。

Ishitsuka K, Utsunomiya A, Ishida T. . PD-1 Inhibitor Therapy in Adult T-Cell Leukemia–Lymphoma. . N Engl J Med.379 ( 7 ) 695 2018.8PD-1 Inhibitor Therapy in Adult T-Cell Leukemia–Lymphoma.Reviewed

Kozako T. . The small molecule STF-62247 induces apoptotic and autophagic cell death in leukemic cells . Oncotarget9 ( 45 ) 27645 - 27655 2018.6

中村大輔, 林田真衣子, 窪田佳代子, 松浦英治, 田淵智久, 有馬直佑, 井上大栄, 吉満誠, 石塚賢治 . レナリドミド・デキサメタゾン療法で改善したPOEMS症候群による肺高血圧症 . 臨床血液59 ( 5 ) 489 - 491 2018.5レナリドミド・デキサメタゾン療法で改善したPOEMS症候群による肺高血圧症Reviewed

中村大輔, 林田真衣子, 窪田佳代子, 松浦英治, 田淵智久, 有馬直佑, 井上大栄, 吉満誠, 石塚賢治 . レナリドミド・デキサメタゾン療法で改善したPOEMS症候群による肺高血圧症 . 臨床血液59 ( 5 ) 489 - 491 2018.5レナリドミド・デキサメタゾン療法で改善したPOEMS症候群による肺高血圧症

Publisher：(一社)日本血液学会-東京事務局

54歳女。易疲労感を主訴とした。甲状腺がんの術後経過観察中に肝脾腫を認め、近医婦人科で子宮筋腫と貧血を指摘された。紹介受診時の各種検査で多発ニューロパチー、血清VEGF上昇、IgA-λ型M蛋白、肝脾腫、下肢浮腫、内分泌異常、皮膚の色素沈着を認めたことからpolyneuropathy、organomegaly、endocrinopathy、M-protein and skin changes症候群と診断した。当初、大量化学療法併用自家造血幹細胞移植を計画していたが、治療前に肺高血圧症が判明した。lenalidomide・dexamethazone療法を先行し、3コース施行後の右心カテーテル検査で肺高血圧症の改善を確認してから大量化学療法併用自家造血幹細胞移植を行った。

Kataoka K, Iwanaga M, Yasunaga JI, Nagata Y, Kitanaka A, Kameda T, Yoshimitsu M, Shiraishi Y, Sato-Otsubo A, Sanada M, Chiba K, Tanaka H, Ochi Y, Aoki K, Suzuki H, Shiozawa Y, Yoshizato T, Sato Y, Yoshida K, Nosaka K, Hishizawa M, Itonaga H, Imaizumi Y, Munakata W, Shide K, Kubuki Y, Hidaka T, Nakamaki T, Ishiyama K, Miyawaki S, Ishii R, Nureki O, Tobinai K, Miyazaki Y, Takaori-Kondo A, Shibata T, Miyano S, Ishitsuka K, Utsunomiya A, Shimoda K, Matsuoka M, Watanabe T, Ogawa S. . Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma. . Blood131 ( 2 ) 215 - 225 2018.1Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma.Invited Reviewed

Kataoka K. . Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma . Blood131 ( 2 ) 215 - 225 2018.1

NAKAMURA Daisuke, HAYASHIDA Maiko, KUBOTA Kayoko, MATSUURA Eiji, TABUCHI Tomohisa, ARIMA Naosuke, INOUE Hirosaka, YOSHIMITSU Makoto, ISHITSUKA Kenji . Successful treatment of POEMS syndrome-associated pulmonary hypertension with lenalidomide and dexamethasone therapy . Rinsho Ketsueki59 ( 5 ) 489 - 491 2018

Publisher：The Japanese Society of Hematology

POEMS syndrome is often complicated by pulmonary hypertension. The standard therapy for patients with POEMS syndrome is high-dose chemotherapy followed by autologous stem cell transplantation. However, the safety of high-dose chemotherapy for patients complicated with pulmonary hypertension remains unclear, and the optimal therapy for these patients is yet to be establishment. Herein, we report the case of a 54-year-old woman with POEMS syndrome accompanied by pulmonary hypertension. We successfully and safely performed lenalidomide and dexamethasone (Ld) therapy followed by high-dose chemotherapy and autologous stem cell transplantation, which improved her pulmonary hypertension. Thus, Ld can be considered as safe and effective for pulmonary hypertension with POEMS syndrome.

DOI： 10.11406/rinketsu.59.489

PubMed

Nosaka K. . Epidemiological and clinical features of adult T-cell leukemia–lymphoma in Japan, 2010–2011: A nationwide survey . Cancer Science108 ( 12 ) 2478 - 2486 2017.12

Nosaka Kisato, Iwanaga Masako, Imaizumi Yoshitaka, Ishitsuka Kenji, Ishizawa Kenichi, Ishida Yoji, Amano Masahiro, Ishida Takashi, Uike Naokuni, Utsunomiya Atae, Ohshima Koichi, Kawai Kazuhiro, Tanaka Junji, Tokura Yoshiki, Tobinai Kensei, Watanabe Toshiki, Uchimaru Kaoru, Tsukasaki Kunihiro . 日本の2010-2011年の成人T細胞白血病-リンパ腫の疫学的および臨床的特徴　全国的な調査(Epidemiological and clinical features of adult T-cell leukemia-lymphoma in Japan, 2010-2011: A nationwide survey) . Cancer Science108 ( 12 ) 2478 - 2486 2017.12日本の2010-2011年の成人T細胞白血病-リンパ腫の疫学的および臨床的特徴　全国的な調査(Epidemiological and clinical features of adult T-cell leukemia-lymphoma in Japan, 2010-2011: A nationwide survey)

Publisher：John Wiley & Sons Australia, Ltd

日本における成人T細胞白血病(ATL)の最近の疫学的特徴を把握するため、全国的なATL調査を行い、ATLの疫学的および臨床的特徴が、時間とともにどのように変化したのかを評価した。2010年から2011年の間に126病院から新規にATLと診断された患者996名のうち922名(男487名、女435名、年齢中央値68歳)を対象とした。その結果、67.2%は九州-沖縄地方で診断されていた。サブタイプは急性型の49.5%が最も多く、リンパ腫型(25.7%)、慢性型(14.2%)と続いた。リンパ腫型は男性、慢性型は女性で多く罹患している傾向が認められた。リンパ腫型の約半数は70歳以上で、慢性型と診断された患者の3分の1は60歳以下であった。これらの特徴は1980年代および1990年代に行った全国調査の結果とは異なっていた。以上より、最近のATL患者の約半数は集中的な細胞傷害性療法ができない68歳以上で、高齢者のための新しい毒性の低い薬剤やATLの発症を予防する更なる戦略が必要と考えられた。

Ishitsuka K. . Safety and efficacy of mogamulizumab in patients with adult T-cell leukemia–lymphoma in Japan: interim results of postmarketing all-case surveillance . International Journal of Hematology106 ( 4 ) 522 - 532 2017.10

Ishitsuka K, Yurimoto S, Kawamura K, Tsuji Y, Iwabuchi M, Takahashi T, Tobinai K. . Safety and efficacy of mogamulizumab in patients with adult T-cell leukemia-lymphoma in Japan: interim results of postmarketing all-case surveillance. . Int J Hematol.106 ( 4 ) 522 - 532 2017.10Safety and efficacy of mogamulizumab in patients with adult T-cell leukemia-lymphoma in Japan: interim results of postmarketing all-case surveillance.Reviewed

Ishitsuka Kenji, Yurimoto Satoshi, Kawamura Kouichi, Tsuji Yukie, Iwabuchi Manabu, Takahashi Takeshi, Tobinai Kensei . 日本における成人T細胞白血病/リンパ腫患者におけるモガムリズマブの安全性と有効性　市販後全症例調査の中間結果(Safety and efficacy of mogamulizumab in patients with adult T-cell leukemia-lymphoma in Japan: interim results of postmarketing all-case surveillance) . International Journal of Hematology106 ( 4 ) 522 - 532 2017.10日本における成人T細胞白血病/リンパ腫患者におけるモガムリズマブの安全性と有効性　市販後全症例調査の中間結果(Safety and efficacy of mogamulizumab in patients with adult T-cell leukemia-lymphoma in Japan: interim results of postmarketing all-case surveillance)

Publisher：(一社)日本血液学会

モガムリズマブ(MO)で治療されたC-Cケモカイン受容体4(CCR4)陽性の再発/難治性成人T細胞白血病/リンパ腫(ATL)患者の市販後調査を行い、有効性を484名(男258名、女226名)、安全性を442名で調べた。ATL亜型は急性が58.9%、リンパ腫が34.2%であった。患者全例にMO 1.0mg/kgを週に1回、単独または他の治療と併用して8週間点滴した。薬物有害反応(ADR)は患者の74.0%で報告され、そのうち35.7%が重篤、6.2%が致死的であった。点滴関連反応は29.3%、皮膚障害は34.3%、感染症は22.1%、免疫障害は3.5%、腫瘍溶解症候群は2.5%で認められた。移植片対宿主病は同種造血幹細胞移植の前にMOを投与された患者42名(男30名、女12名)中25名で報告された。全奏効率は57.7%で、単独治療群が57.5%、併用治療群が58.2%であった。MOの忍容性は許容できるが、重篤なADRのリスクがあるため注意深く監視すべきと考えられた。

Mihashi Y, Mizoguchi M, Takamatsu Y, Ishitsuka K, Iwasaki H, Koga M, Urabe K, Momosaki S, Sakata T, Kiyomi F, Takeshita M. . C-MYC and Its Main Ubiquitin Ligase, FBXW7, Influence Cell Proliferation and Prognosis in Adult T-cell Leukemia/Lymphoma. . Am J Surg Pathol. 41 ( 8 ) 1139 - 1149 2017.8C-MYC and Its Main Ubiquitin Ligase, FBXW7, Influence Cell Proliferation and Prognosis in Adult T-cell Leukemia/Lymphoma.Reviewed

Katsuya H. . Prognostic index for chronic- and smoldering-type adult T-cell leukemia-lymphoma . Blood130 ( 1 ) 39 - 47 2017.7

Ishitsuka K. . Treatment of indolent adult T-cell leukemia/lymphoma (ATL) . Adult T-cell Leukemia/Lymphoma 117 - 124 2017.4

Tokunaga M, Yonekura K, Nakamura D, Haraguchi K, Tabuchi T, Fujino S, Hayashida M, Maekawa K, Arai A, Nakano N, Kamada Y, Kubota A, Inoue H, Owatari S, Takeuchi S, Takatsuka Y, Otsuka M, Hanada S, Matsumoto T, Yoshimitsu M, Ishitsuka K, Utsunomiya A. . Clinical significance of cutaneous adverse reaction to mogamulizumab in relapsed or refractory adult T-cell leukaemia-lymphoma. . Br J Haematol 2017.4Clinical significance of cutaneous adverse reaction to mogamulizumab in relapsed or refractory adult T-cell leukaemia-lymphoma.Reviewed

中村桃子, 保坂加奈子, 秋元正樹, 吉満誠, 大坪秀雄, 石塚賢治 . アバタセプト投与中に免疫不全関連リンパ増殖性疾患を再発した関節リウマチの1例 . 九州リウマチ37 ( 1 ) 67 - 71 2017.3アバタセプト投与中に免疫不全関連リンパ増殖性疾患を再発した関節リウマチの1例

Publisher：九州リウマチ学会

68歳男性。1991年関節リウマチ(RA)と診断、メトトレキサート(MTX)を開始、2004年インフリキシマブ(IFX)が追加された。2013年に縦隔・腹腔内にリンパ節腫大を認め医原性免疫不全関連リンパ増殖性疾患(OIIA-LPD)を疑い、MTXとIFXを中止し自然退縮した。RAの悪化を認め、免疫抑制剤が追加されたが副作用で中止となり、2014年1月アバタセプト(ABT)単独療法開始、2年後、sIL-2Rの上昇と縦隔リンパ節腫大からOIIA-LPDと診断した。ABTの中止のみでLPDは退縮したが、消化管大量出血による出血性ショックと播種性血管内凝固症候群のため死亡した。病理解剖で残存していた縦隔リンパ節はEBV陽性ホジキンリンパ腫と診断された。OIIA-LPD寛解後のRAの治療においてABTは比較的安全との症例報告が散見されるが、ABTでもLPDを誘発する可能性があり、注意が必要である。(著者抄録)

Miyamoto S, Yotsumoto F, Ueda T, Fukami T, Sanui A, Miyata K, Nam SO, Fukagawa S, Katsuta T, Maehara M, Kondo H, Miyahara D, Shirota K, Yoshizato T, Kuroki M, Nishikawa H, Saku K, Tsuboi Y, Ishitsuka K, Takamatsu Y, Tamura K, Matsunaga A, Hachisuga T, Nishino S, Odawara T, Maeda K, Manabe S, Ishikawa T, Okuno Y, Ohishi M, Hikita T, Mizushima H, Iwamoto R, Mekada E. . BK-UM in patients with recurrent ovarian cancer or peritoneal cancer: a first-in-human phase-I study. . BMC Cancer. 31 ( 17 ) 3071 - 3075 2017.1BK-UM in patients with recurrent ovarian cancer or peritoneal cancer: a first-in-human phase-I study.Reviewed

Miyamoto S. . BK-UM in patients with recurrent ovarian cancer or peritoneal cancer: A first-in-human phase-I study . BMC Cancer17 ( 1 ) 89 2017.1

Nakano D. . Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (V): coumarins and alkaloids from Boenninghausenia japonica and Ruta graveolens . Journal of Natural Medicines71 ( 1 ) 170 - 180 2017.1

Nakano D, Ishitsuka K, Matsuda N, Kouguchi A, Tsuchihashi R, Okawa M, Okabe H, Tamura K, Kinjo J. . Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (V): coumarins and alkaloids from Boenninghausenia japonica and Ruta graveolens. . J Nat Med. 71 ( 1 ) 170 - 180 2017.1Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (V): coumarins and alkaloids from Boenninghausenia japonica and Ruta graveolens.Reviewed

Language：English Publishing type：Research paper (scientific journal)

During the course of our studies towards the identification of promising chemotherapeutic candidates from plants against two human T-cell lymphotropic virus type I-infected T-cell lines (MT-1 and MT-2), we screened 17 extracts from 9 rutaceous plants against MT-1 and MT-2 cells. The extracts from the aerial parts and roots of Boenninghausenia japonica, as well as the leaves and roots of Ruta graveolens showed potent antiproliferative effects. After activity-guided fractionation, we isolated 44 compounds from two rutaceous plants, including three new compounds (1-3), which were classified into 26 coumarin analogs (13 coumarins, 8 furanocoumarins, 4 dihydrofuranocoumarins and one dihydropyranocoumarin), 15 alkaloid analogs (7 quinolone alkaloids, 4 acridone alkaloids, 3 furanoquinoline alkaloids and one tetrahydroacridone alkaloid) and 3 flavonoid glycosides. Structure-activity relationship studies were also evaluated. The coumarin compounds (2, 3 and 7-9) bearing a 3-dimethylallyl moiety showed potent activity. Similarly, of all the furanocoumarins evaluated in the current study, compound 17 bearing a 3-dimethylallyl group also showed potent activity. A dihydrofuranocoumarin (27) bearing a 3-dimethylallyl moiety showed the most potent activity. Following 27, compound 28 showed potent activity. These results therefore suggested that the presence of a 3-dimethylallyl moiety was important to the antiproliferative activity of these coumarin analogs.

Nakano Daisuke, Ishitsuka Kenji, Matsuda Narumi, Kouguchi Ai, Tsuchihashi Ryota, Okawa Masafumi, Okabe Hikaru, Tamura Kazuo, Kinjo Junei . ヒト成人T細胞白血病/リンパ腫に対する化学療法に有望な植物由来の候補化合物のスクリーニング(第5報)　Boenninghausenia japonicaとRuta graveolensからのクマリンとアルカロイド化合物(Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma(V): coumarins and alkaloids from Boenninghausenia japonica and Ruta graveolens) . Journal of Natural Medicines71 ( 1 ) 170 - 180 2017.1ヒト成人T細胞白血病/リンパ腫に対する化学療法に有望な植物由来の候補化合物のスクリーニング(第5報)　Boenninghausenia japonicaとRuta graveolensからのクマリンとアルカロイド化合物(Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma(V): coumarins and alkaloids from Boenninghausenia japonica and Ruta graveolens)

Publisher：シュプリンガー・ジャパン(株)

ミカン科植物の17種類の抽出物を対象に、2種類のヒトTリンパ球向性ウイルス1型株(MT-1とMT-2)に対する抗増殖活性をスクリーニングした。Boenninghausenia japonicaの地上部と根、およびRuta graveolensの葉と根の抽出物が強い抗増殖活性を示した。これらの抽出物について活性ガイド分画を行い、3種類の新規化合物を含む44種類の化合物を得た。うち26種類はクマリンアナログ、15種類はアルカロイドアナログ、3種類はフラボノイドグリコシドであった。構造活性相関を解析したところ、3-ジメチルアリル部分を持つクマリン化合物とジヒドロフラノクマリン、および3-ジメチルアリル基を持つフラノクマリンが強い抑制活性を示した。これらのクマリンアナログの抗増殖活性には、3-ジメチルアリル部分の存在が重要であると考えられた。

ISHITSUKA Kenji . Molecular pathogenesis and its therapeutic implication for ATL . Rinsho Ketsueki58 ( 10 ) 2004 - 2011 2017

Publisher：The Japanese Society of Hematology

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-lymphotropic virus type I (HTLV-1). HTLV-1 related proteins Tax and HTLV-1 bZIP factor induce immortalization and transformation of HTLV-1-infected T-lymphocytes and eventually induce clonal proliferation. One of the apparent molecular features in ATL cells is abundant genomic abnormalities targeting characteristic pathways, including T-cell receptor signaling and the NF-κB pathway, G-protein coupled-receptor, including CCR4, and transcriptional regulation. Moreover, the overexpression of PD-L1 caused by structural variations in the 3'-UTR of the PD-L1 gene has been reported recently, which indicates possible escape of ATL cells from immune-surveillance and its therapeutic application for pharmacological intervention. The next is the downregulation of microRNAs and tumor suppressors by genome-wide epigenetic abnormalities, especially accumulation of trimethylated H3K27 induced by EZH2. Among these molecular events frequently observed in ATL cells, treatment targeting CCR4 via a monoclonal antibody has been introduced in the clinic, and immune-therapy by therapeutic vaccine with Tax peptide-pulsed dendritic cells, treatment by immune checkpoint inhibitors, and treatment targeting EZH1/2 by a small molecule inhibitor are under clinical trial. Establishment of novel treatment strategies beyond cytotoxic agents for ATL are eagerly anticipated, especially for elderly patients.

DOI： 10.11406/rinketsu.58.2004

PubMed

Ishitsuka Kenji . V. Adult T-cell Leukemia: Diagnosis and Treatment . Nihon Naika Gakkai Zasshi106 ( 7 ) 1397 - 1403 2017

Katsuya Hiroo, Ishitsuka Kenji . Treatment advances and prognosis for patients with adult T-cell leukemia-lymphoma . Ｊｏｕｒｎａｌ　ｏｆ　Ｃｌｉｎｉｃａｌ　ａｎｄ　Ｅｘｐｅｒｉｍｅｎｔａｌ　Ｈｅｍａｔｏｐａｔｈｏｌｏｇｙ57 ( 3 ) 87 - 97 2017

Publisher：日本リンパ網内系学会

A classification for adult T-cell leukemia-lymphoma (ATL) based on clinical features was proposed in 1991: acute, lymphoma, chronic, and smoldering types, and their median survival times (MSTs) were reported to be 6.2, 10.2, 24.3 months, and not reached, respectively. Several new therapies for ATL have since been developed, i.e. dose-intensity multi-agent chemotherapies, allogeneic hematopoietic stem cell transplantation (allo-HSCT), monoclonal antibodies, and anti-viral therapy. The monoclonal antibody to CCR4, mogamulizumab, clearly improved response rates in patients with treatment-naïve and relapsed aggressive ATL, and has the potential to provide a survival advantage. The outcomes of allo-HSCT have been reported since the early 2000s. High treatment-related mortality was initially the crucial issue associated with this treatment approach; however, reduced intensity conditioning regimens have decreased the risk of treatment-related mortality. The introduction of allo- HSCT has had a positive impact on the prognosis of and potential curability with treatments for ATL. A meta-analysis of a treatment with interferon-α and zidovudine (IFN/AZT) revealed a survival benefit in patients with the leukemic subtype. A phase 3 study comparing IFN/AZT with watchful waiting in patients with indolent ATL is ongoing in Japan. Several clinical trials on novel agents are currently being conducted, such as the histone deacetylase inhibitors, alemtuzumab, brentuximab vedotin, nivolumab, and an EZH1/2 dual inhibitor.

DOI： 10.3960/jslrt.17008

PubMed

Mihashi Y. . C-MYC and Its Main Ubiquitin Ligase, FBXW7, Influence Cell Proliferation and Prognosis in Adult T-cell Leukemia/Lymphoma . American Journal of Surgical Pathology41 ( 8 ) 1139 - 1149 2017

ISHITSUKA Kenji . Progress in the management of ATL . Rinsho Ketsueki58 ( 6 ) 676 - 682 2017

Publisher：The Japanese Society of Hematology

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-lymphotropic virus type I (HTLV-1), and its prognosis remains poor. Three to five percent of HTLV-1 carriers, infected mainly by breast feeding, develop ATL after a latency period as long as 70 years. The standard of care for aggressive ATL and indolent ATL comprises intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation, if applicable, and watchful waiting, respectively. Outside Japan, a combination of interferon-α and zidovudine has also been used as a therapeutic option for acute, chronic, and smoldering-type ATLs. A Japanese nationwide retrospective study revealed the outcome of patients diagnosed between 2000 and 2009. The median survival times were 8.3, 10.6, 31.5, and 55.0 months and the 4-year overall survival rates were 11%, 16%, 36%, and 52% for acute, lymphoma, chronic, and smoldering-type ATLs, respectively. Recently, the development of several novel agents has been attempted by targeting surface antigens on ATL cells such as CCR4 and CD30 with monoclonal antibodies, targeting molecular abnormalities in ATL cells with EZH1/2 inhibitor, and modulating the immune environment via immunomodulatory drugs (IMiDs) or immune checkpoint inhibitors. Among them, a CCR4 monoclonal antibody mogamulizumab, and an IMiD, lenalidomide, have been introduced for clinical use in Japan.

DOI： 10.11406/rinketsu.58.676

PubMed

石塚賢治 . ATLに対する新規治療の開発 . Ｓｋｉｎ　Ｃａｎｃｅｒ31 ( 3 ) 209 - 215 2017

坂江遥, 玉井努, 小田耕平, 鈴木紳介, 平木翼, 谷山央樹, 伊集院翔, 大西容雅, 椨一晃, 室町香織, 馬渡誠一, 森内昭博, 石塚賢治, 谷本昭英, 井戸章雄 . 脾破裂を伴い急性肝不全様の経過を呈した悪性リンパ腫の一例 . 肝臓57 ( 12 ) 674 - 683 2016.12脾破裂を伴い急性肝不全様の経過を呈した悪性リンパ腫の一例

Publisher：(一社)日本肝臓学会

症例は66歳、男性。全身倦怠感、発熱、腹痛、食思不振で近医を受診し、血小板減少、肝腎機能障害を認め、当院へ緊急入院となった。腹部超音波検査、CT検査で著明な肝脾腫と脾内占拠性病変、脾出血を認めた。急速に肝不全が進行、播種性血管内凝固症候群(disseminated intravascular coagulation:DIC)も合併し、全身状態は増悪した。第3病日には腹腔内出血を来し、第5病日に死亡した。家族の同意を得て、剖検を行った。肝腫大、著明な脾腫大を認め、脾臓は被膜の破綻、出血を伴い脾破裂をきたしていた。肝臓、脾臓には腫瘍細胞がびまん性に増殖しており、免疫染色にて悪性リンパ腫(diffuse large B-cell lymphoma:DLBCL)と診断した。今回、我々は脾破裂を伴い急性肝不全様の急激な経過を呈した悪性リンパ腫の一例を経験したので文献的考察を含めて報告する。(著者抄録)

Ishitsuka K. . Diagnosis and follow-up of posterior inferior cerebellar artery dissection complicated with ischemic stroke assisted by T1-VISTA: A report of two cases . BMC Neurology16 ( 1 ) 2016.7

Satou A. . FoxP3-positive T cell lymphoma arising in non-HTLV1 carrier: Clinicopathological analysis of 11 cases of PTCL-NOS and 2 cases of mycosis fungoides . Histopathology68 ( 7 ) 1099 - 1108 2016.6

Ishibashi H, Nimura S, Ishitsuka K, Mihashi Y, Mizoguchi M, Nakamura S, Okamura S, Momosaki S, Aoyagi K, Sakisaka S, Takeshita M. . High Expression of Intestinal Homing Receptor CD103 in Adult T-Cell Leukemia/Lymphoma, Similar to 2 Other CD8+ T-Cell Lymphomas. . The American Journal of Surgical Pathology40 ( 4 ) 462 - 470 2016.4High Expression of Intestinal Homing Receptor CD103 in Adult T-Cell Leukemia/Lymphoma, Similar to 2 Other CD8+ T-Cell Lymphomas.Reviewed

Ishibashi H. . High expression of intestinal homing receptor CD103 in adult T-cell Leukemia/Lymphoma, similar to 2 other CD8+T-cell lymphomas . American Journal of Surgical Pathology40 ( 4 ) 462 - 470 2016

Sakae Haruka, Muromachi Kaori, Mawatari Seiichi, Moriuchi Akihiro, Ishitsuka Kenji, Tanimoto Akihide, Ido Akio, Tamai Tsutomu, Oda Kohei, Suzuki Shinsuke, Hiraki Tsubasa, Taniyama Oki, Ijuin Sho, Onishi Hiroka, Tabu Kazuaki . Malignant lymphoma with splenic rupture presenting as acute hepatic failure . Kanzo57 ( 12 ) 674 - 683 2016

Publisher：The Japan Society of Hepatology

A 66-year-old man consulted a local doctor, complaining of general malaise, fever, abdominal pain, and anorexia. Laboratory data showed thrombocytopenia and hepatorenal dysfunction, and the patient was referred to our hospital. Abdominal ultrasound and computed tomography showed splenohepatomegaly with cystic masses and bleeding in the spleen. Despite treatment, hepatic failure progressed and disseminated intravascular coagulation developed, and the patient's condition worsened. Intraperitoneal bleeding occurred on the third hospital day, and the patient died two days later. We performed an autopsy after informed consent was obtained from the family. At autopsy, the liver and spleen showed hepatomegaly and marked splenomegaly with tunic damage and bleeding, diagnosed as splenic rupture, and diffuse infiltration of lymphoma cells. The tumor was diagnosed as diffuse large B-cell lymphoma. We report a rare case of malignant lymphoma with splenic rupture presenting as acute hepatic failure.

DOI： 10.2957/kanzo.57.674

Scopus

Katsuya H, Ishitsuka K, Utsunomiya A, Hanada S, Eto T, Moriuchi Y, Saburi Y, Miyahara M, Sueoka E, Uike N, Yoshida S, Yamashita K, Tsukasaki K, Suzushima H, Ohno Y, Matsuoka H, Jo T, Amano M, Hino R, Shimokawa M, Kawai K, Suzumiya J, Tamura K; ATL-Prognostic Index Project. . Treatment and survival among 1594 patients with ATL. . Blood126 ( 24 ) 2570 - 2577 2015.12Treatment and survival among 1594 patients with ATL.Reviewed

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

We investigated the expression of the αEβ7 integrin (CD103)-intestinal homing receptor of T-intraepithelial lymphocytes (IELs) in 130 cases of adult T-cell leukemia/lymphoma (ATLL). We detected CD103 lymphoma cells in 55% (31/56) of mainly gastrointestinal (GI)-involved ATLL cases. Among them, lymphoma cells of 18 cases located in other involved organs had similar CD103 expression patterns. Histologically, we found (a) increased reactive IELs in non-neoplastic mucosal layers in 28% (5/18) of surgical and mucosal resection cases, (b) preserved epithelial glands, and (c) numerous small intraepithelial ATLL nests in involved lesions in 36 (69%) and 21 (40%), respectively, of the 52 examined cases. These 3 patterns were common in intestinal type II enteropathy-associated T-cell lymphoma but were rare in intestinal EBV nasal-type/like T/natural killer (NK)-cell lymphoma. We detected CD103 tumor cells in 41% (16/39) of lymph node-involved ATLL, in 31% (11/35) of skin-involved ATLL, in 68% (21/31) of type II CD4 enteropathy-associated T-cell lymphoma cases, in 36% (8/22) of primary gastric T/NK-cell lymphomas, and in 77% (7/9) of CD8 epidermotropic mycosis fungoides. CD103 ATLL prefers involving the GI tract over the skin (P<0.05). CD103 expression in GI-involved and/or total ATLL cases was significantly higher than in other 9 T/NK-cell lymphoma groups (P<0.05 or 0.01). Only ATLL cases were commonly CD103 in CD4 T/NK-cell lymphoma groups (P<0.05 or 0.01). Human T-lymphotropic virus-1-infected CD103 T-IELs and mucosal T cells may be important sources of ATLL.

Katsuya H. . Treatment and survival among 1594 patients with ATL . Blood126 ( 24 ) 2570 - 2577 2015.12

Ishitsuka K. . Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4 monoclonal antibody, mogamulizumab . International Journal of Hematology102 ( 4 ) 493 - 497 2015.10

Satou A, Asano N, Kato S, Katsuya H, Ishitsuka K, Elsayed AA, Nakamura S. . FoxP3-positive T-cell Lymphoma Arising in non-HTLV1 carrier: Clinicopathological analysis of 11 cases of PTCL-NOS and 2 cases of Mycosis Fungoides. . Histopathology 2015.10FoxP3-positive T-cell Lymphoma Arising in non-HTLV1 carrier: Clinicopathological analysis of 11 cases of PTCL-NOS and 2 cases of Mycosis Fungoides.Reviewed

Ishitsuka K, Murahashi M, Katsuya H, Mogi A, Masaki M, Kawai C, Goto T, Ishizu M, Ikari Y, Takamatsu Y, Ishibashi H, Nimura S, Takeshita M, Tamura K. . Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4 monoclonal antibody, mogamulizumab. . International Journal of Hematology102 ( 4 ) 493 - 497 2015.10Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4 monoclonal antibody, mogamulizumab.Reviewed

Ishitsuka Kenji, Murahashi Mutsunori, Katsuya Hiroo, Mogi Ai, Masaki Michio, Kawai Chisato, Goto Toshitaka, Ishizu Masanao, Ikari Yosuke, Takamatsu Yasushi, Ishibashi Hideki, Nimura Satoshi, Takeshita Morishige, Tamura Kazuo . 抗CCR4モノクローナル抗体モガムリズマブを投与中の移植片対宿主病との鑑別が必要な大腸炎(Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4 monoclonal antibody, mogamulizumab) . International Journal of Hematology102 ( 4 ) 493 - 497 2015.10抗CCR4モノクローナル抗体モガムリズマブを投与中の移植片対宿主病との鑑別が必要な大腸炎(Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4 monoclonal antibody, mogamulizumab)

Publisher：(一社)日本血液学会

症例は57歳男性で、急性成人T細胞白血病リンパ腫(ATL)と診断された。患者が同種幹細胞移植を拒絶したためTHP-COP療法を開始した。その後は部分寛解に達したが、THP-COP療法終了直後にリンパ節と皮膚のATL病変が増大したため、当院に紹介となった。末梢血中のATL細胞において抗CCケモカイン受容体4(CCR4)が強力に発現していたため、day1、8、15、22に4回のモガムリズマブ投与を行った。その後、ゲムシタビン、カルボプラチン、デキサメサゾンによる併用化学療法を開始した。モガムリズマブの投与後に2〜3L/日の持続する水様性非血性下痢が出現したが、便中から病原性細菌や寄生虫は検出されなかった。大腸粘膜の生検検体では、結腸腺に多数のアポトーシス小体の小さい巣が認められ、これは急性大腸性移植片対宿主病とよく似ていた。この原因として、モガムリズマブによる制御性T細胞の欠乏による自己反応性免疫系の活性化が疑われた。

Ishitsuka K. . A phase II study of bortezomib in patients with relapsed or refractory aggressive adult T-cell leukemia/lymphoma . Cancer Science106 ( 9 ) 1219 - 1223 2015.9

Ishitsuka K, Utsunomiya A, Katsuya H, Takeuchi S, Takatsuka Y, Hidaka M, Sakai T, Yoshimitsu M, Ishida T, Tamura K. . A phase II study of bortezomib in patients with relapsed or refractory aggressive adult T-cell leukemia/lymphoma. . Cancer Science106 ( 9 ) 1219 - 1223 2015.9A phase II study of bortezomib in patients with relapsed or refractory aggressive adult T-cell leukemia/lymphoma.Reviewed

Ishitsuka Kenji, Utsunomiya Atae, Katsuya Hiroo, Takeuchi Shogo, Takatsuka Yoshifusa, Hidaka Michihiro, Sakai Tatsunori, Yoshimitsu Makoto, Ishida Takashi, Tamura Kazuo . 再発性または難治性のアグレッシブ成人T細胞白血病/リンパ腫患者におけるボルテゾミブの臨床第II相試験(A phase II study of bortezomib in patients with relapsed or refractory aggressive adult T-cell leukemia/lymphoma) . Cancer Science106 ( 9 ) 1219 - 1223 2015.9再発性または難治性のアグレッシブ成人T細胞白血病/リンパ腫患者におけるボルテゾミブの臨床第II相試験(A phase II study of bortezomib in patients with relapsed or refractory aggressive adult T-cell leukemia/lymphoma)

Publisher：John Wiley & Sons Australia, Ltd

少なくとも1レジメンの化学療法を施行された再発/難治性成人T細胞白血病/リンパ腫(ATL)患者15名(男10名、女5名、49〜73歳)を対象に、ボルテゾミブ単剤療法の有効性と安全性を評価する臨床第II相試験を行った。主要評価項目は全奏効率(ORR)、副次評価項目は安全性、病変での最良効果、無増悪生存期間(PFS)であった。全奏効率として部分寛解(PR)が1名、安定が5名で認められ、ORRは6.7%であった。部位別の効果は末梢血の完全寛解が1名、測定可能な標的病変のPRが2名、皮膚病変のPRが2名で、PFRは38日であった。全ての患者で有害事象(AE)が1回以上認められ、80%でグレード3/4のAEが1回以上みられたが、新しい安全性所見はなかった。ボルテゾミブは単独でこのコホートの患者に対し非常に有望とは思われなかったため、この試験の終了を決定した。

Nakano D. . Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (IV): Phenanthroindolizidine alkaloids from Tylophora tanakae leaves . Journal of Natural Medicines69 ( 3 ) 397 - 401 2015.7

Nakano Daisuke, Ishitsuka Kenji, Ikeda Mizuki, Tsuchihashi Ryota, Okawa Masafumi, Okabe Hikaru, Tamura Kazuo, Kinjo Junei . ヒト成人T細胞白血病/リンパ腫に対する化学療法の候補となる植物成分のスクリーニング(IV)　Tylophora tanakaeの葉からのフェナンスロインドリジジンアルカロイド(Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma(IV): phenanthroindolizidine alkaloids from Tylophora tanakae leaves) . Journal of Natural Medicines69 ( 3 ) 397 - 401 2015.7ヒト成人T細胞白血病/リンパ腫に対する化学療法の候補となる植物成分のスクリーニング(IV)　Tylophora tanakaeの葉からのフェナンスロインドリジジンアルカロイド(Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma(IV): phenanthroindolizidine alkaloids from Tylophora tanakae leaves)

Publisher：シュプリンガー・ジャパン(株)

ガガイモ科植物の15種の抽出物の、ヒトTリンパ球向性ウイルス1型(HTLV-1)感染T細胞系(MT-1およびMT-2)に対する作用を検討した。Tylophora tanakaeの地上部のメタノール抽出物が抗増殖効果を示した。activity-guided fractionationを行ったところ、6種のフェナンスロインドリジジンアルカロイド(1種の新規化合物を含む)が単離された。MT-1およびMT-2細胞に対する抗増殖活性を測定した結果、一部の化合物のEC50は低いナノモル濃度を示し、抗癌薬ドキソルビシンに匹敵した。構造活性相関では、14β-ヒドロキシ基が必須であった。一方、2-メトキシ基、7-メトキシ基、N-オキシド基は抗増殖活性を低下させるようであった。

Ishida T. . Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: A randomized phase II study . British Journal of Haematology169 ( 5 ) 672 - 682 2015.6

石塚賢治、山野嘉久、宇都宮與、内丸薫 . HTLV-1キャリア外来の実態調査 . 臨床血液56 ( 6 ) 666 - 672 2015.6HTLV-1キャリア外来の実態調査Reviewed

Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal)

Human T-lymphotropic virus type-I(HTLV-1)は成人T細胞白血病・リンパ腫(ATL),HTLV-1関連脊髄症/熱帯性痙性脊髄麻痺などの原因ウイルスで,主に授乳や性交渉によって感染が成立する。本研究では国内4施設におけるHTLV-1感染者(キャリア)対応の実態を調べた。キャリア外来標榜施設では,献血時もしくは妊娠時の検査でHTLV-1感染を知り,HTLV-1関連疾患発症の有無についての検査やHTLV-1感染に伴う不安への説明や相談,関連疾患に対する説明を希望し受診する場合が多かった。受診者の約半数はHTLV-1感染を2年以上前に告知されており,近年のHTLV-1やキャリア外来への社会での認知から,キャリア自身の意識が変わったことが受診につながったものと考えられる。一方で,HTLV-1高度浸淫地域においてはかかりつけ医によって十分な対応がなされている可能性が高いと考えられた。HTLV-1非浸淫地域にある2施設ではHTLV-1キャリアと診断された受診者の50%以上が両親とも出生地は九州以外であり,HTLV-1キャリアは九州出身者に多いとされてきた事実の変貌が明らかになった。今後HTLV-1キャリア数は減少するものの,居住地の偏在は少なくなると考えられ,医療ニーズに適切かつ効率よく対応する体制の構築が重要である。

石塚賢治, 山野嘉久, 宇都宮與, 内丸薫 . HTLV-1キャリア外来の実態調査 . 臨床血液56 ( 6 ) 666 - 672 2015.6HTLV-1キャリア外来の実態調査

Publisher：(一社)日本血液学会-東京事務局

ISHITSUKA Kenji, YAMANO Yoshihisa, UTSUNOMIYA Atae, UCHIMARU Kaoru . A survey of HTLV-1 carrier clinics in Japan . Rinsho Ketsueki56 ( 6 ) 666 - 672 2015

Publisher：The Japanese Society of Hematology

Human T-lymphotropic virus type-I (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraparesis. Currently, mother-to-child transmission via breastfeeding and sexual intercourse are considered to be the two major routes for HTLV-1 infection. We surveyed four clinics in Japan (two HTLV-1 carrier clinics in non-endemic areas and one in an endemic area, and one hematology clinic in a highly endemic area) and reviewed the management of carriers. In HTLV-1 carrier clinics, more than half of visitors had learned of their infections based on an examination conducted either for blood donation or pregnancy. Although half of visitors had known of their infection more than 2 years prior to their visit, they became to visit the clinics probably due to recent awareness of HTLV-1 in public and of carrier clinics. They requested a detailed explanation, and check-ups for infection and its related diseases. In contrast, most visitors in highly endemic areas had apparently received good explanations from their primary care physicians. It is noteworthy that neither parent of more than half of the carriers who visited the two clinics in the non-endemic area had been born outside of Kyushu, a highly endemic area, indicating that carriers will disperse from known endemic areas. Configuring an appropriate and efficient system to support carriers is necessary, especially in non-endemic areas.

DOI： 10.11406/rinketsu.56.666

Scopus

PubMed

Nonokuma Masanari, Kuwabara Yasuo, Takano Koichi, Tamura Kazuo, Ishitsuka Kenji, Yoshimitsu Kengo . 統計的画像解析を用いた体の悪性リンパ腫患者における局所脳グルコース代謝の評価(Evaluation of regional cerebral glucose metabolism in patients with malignant lymphoma of the body using statistical image analysis) . Annals of Nuclear Medicine28 ( 10 ) 950 - 960 2014.12統計的画像解析を用いた体の悪性リンパ腫患者における局所脳グルコース代謝の評価(Evaluation of regional cerebral glucose metabolism in patients with malignant lymphoma of the body using statistical image analysis)

Publisher：(一社)日本核医学会

治療前にFDG-PET/CT検査を受けた体の悪性リンパ腫患者30名(瀰漫性B細胞リンパ腫16名およびその他のリンパ腫14名)を対象とし、局所脳グルコース代謝をレトロスペクティブに評価した。局所脳グルコース代謝は両側性前頭および頭頂葉皮質において糖分解体積の増加に伴い減少することが示された。化学療法後の統計的画像解析により、良好なレスポンダーでは両側性前頭および後頭皮質の局所脳グルコース代謝の回復が認められたが、低レスポンダーでは治療前後の局所脳グルコース代謝変化は認められなかった。さらに、健常人との比較により、治療前の悪性リンパ腫患者では頭頂-後頭皮質において局所脳グルコース代謝が低下していることが示された。本検討により、悪性リンパ腫患者では脳の機能的変化および/または無症候性の脳の損傷を生じていることが示唆された。

Nonokuma M. . Evaluation of regional cerebral glucose metabolism in patients with malignant lymphoma of the body using statistical image analysis . Annals of Nuclear Medicine28 ( 10 ) 950 - 960 2014.11

Ishitsuka K. . Human T-cell leukaemia virus type I and adult T-cell leukaemia-lymphoma . The Lancet Oncology15 ( 11 ) e517 - e526 2014.10

Kunami N. . Promise of combining a Bcl-2 family inhibitor with bortezomib or SAHA for adult T-cell leukemia/lymphoma . Anticancer Research34 ( 10 ) 5287 - 5294 2014.10

Kunami N, Katsuya H, Nogami R, Ishitsuka K, Tamura K . Promise of combining a Bcl-2 family inhibitor with bortezomib or SAHA for adult T-cell leukemia/lymphoma. . Anticancer research34 ( 10 ) 5287 - 94 2014.10Promise of combining a Bcl-2 family inhibitor with bortezomib or SAHA for adult T-cell leukemia/lymphoma.

Fukushima T. . Japan Clinical Oncology Group (JCOG) prognostic index and characterization of long-term survivors of aggressive adult T-cell leukaemia-lymphoma (JCOG0902A) . British Journal of Haematology166 ( 5 ) 739 - 748 2014.9

Ikari Y. . Safety and pharmacokinetic evaluation of repeated intravenous administration of palonosetron 0.75 mg in patients receiving highly or moderately emetogenic chemotherapy . Supportive Care in Cancer22 ( 7 ) 1959 - 1964 2014.7

Kato H. . Gene expression profiling of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways . Cancer Science105 ( 5 ) 537 - 544 2014.5

Kato Harumi, Karube Kennosuke, Yamamoto Kazuhito, Takizawa Jun, Tsuzuki Shinobu, Yatabe Yasushi, Kanda Teru, Katayama Miyuki, Ozawa Yukiyasu, Ishitsuka Kenji, Okamoto Masataka, Kinoshita Tomohiro, Ohshima Koichi, Nakamura Shigeo, Morishima Yasuo, Seto Masao . 高齢者のEpstein-Barrウイルス陽性びまん性大細胞型B細胞リンパ腫の遺伝子発現プロファイリングから明らかになった特徴的な発癌経路の変化(Gene expression profiling of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways) . Cancer Science105 ( 5 ) 537 - 544 2014.5高齢者のEpstein-Barrウイルス陽性びまん性大細胞型B細胞リンパ腫の遺伝子発現プロファイリングから明らかになった特徴的な発癌経路の変化(Gene expression profiling of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways)

Publisher：John Wiley & Sons Australia, Ltd

ヒトオリゴヌクレオチドマイクロアレイ分析を用いて、高齢者のEpstein-Barrウイルス(EBV)陽性びまん性大細胞型B細胞リンパ腫(EBV(+)DLBCL-E)5つとEBV(-)DLBCL7つの遺伝子発現プロファイリングを行い、EBV(+)DLBCL-Eにおける経路の特徴を調べた。遺伝子セット濃縮解析や遺伝子オントロジー解析から、EBV(+)DLBCL-EではJanusキナーゼシグナルトランスデューサー-転写活性化因子(JAK-STAT)と核因子κB経路が豊富であった。これはin vitro分析でも確かめられ、DLBCL細胞株にEBVを感染させるとJAK-STATとNF-κB経路の高活性化が誘導された。ウェスタンブロット分析ではEBV感染細胞株でリン酸化STAT3蛋白質の発現レベル上昇を認めた。免疫組織化学により、EBV(+)DLBCL-E臨床試料のリンパ腫細胞でリン酸化STATS3蛋白質の発現をしばしば認められた。JAK-STATとNF-κB経路を標的とする治療はEBV(+)DLBCL-Eの臨床転帰を改善する可能性があると考えた。

Ishitsuka K. . High blood pressure after acute ischemic stroke is associated with poor clinical outcomes: Fukuoka stroke registry . Hypertension63 ( 1 ) 54 - 60 2014.1

ISHITSUKA Kenji . ATL progress 2013 . Rinsho Ketsueki54 ( 10 ) 1817 - 1828 2013.10

Ishitsuka K . [ATL progress 2013]. . [Rinsho ketsueki] The Japanese journal of clinical hematology54 ( 10 ) 1817 - 27 2013.10[ATL progress 2013].

Nakano Daisuke, Ishitsuka Kenji, Kamikawa Mio, Matsuda Michika, Tsuchihashi Ryota, Okawa Masafumi, Okabe Hikaru, Tamura Kazuo, Kinjo Junei . ヒト成人T細胞白血病/リンパ腫に対する有望な植物由来化学療法薬候補のスクリーニング　第III報(Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (III)) . Journal of Natural Medicines67 ( 4 ) 894 - 903 2013.10ヒト成人T細胞白血病/リンパ腫に対する有望な植物由来化学療法薬候補のスクリーニング　第III報(Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (III))

Publisher：シュプリンガー・ジャパン(株)

ヒト成人T細胞白血病/リンパ腫(ATL)に対する有望な化学療法薬候補を検討するため、植物のスクリーニングを行った。61属182種類の植物から調製した245の抽出物について、2種類のヒトT細胞白血病ウイルスI型(HTLV-I)感染T細胞株(MT-1、MT-2)に対する活性を評価した。245の抽出物のうち、MT-1細胞に強力な抗増殖作用を示したのは52、MT-2細胞に強力な抗増殖作用を示したのは60であった。そのうち、いずれの細胞に対しても強力な阻害活性を示したのは2つ(EC50 0.1〜1μg/mL、+++)、中等度の阻害活性を示したのは7つ(EC50 1〜10μg/mL、++)、弱い阻害活性を示したのは43で(EC50 10〜100μg/mL、+)、残りの抽出物はMT-1細胞に活性を示さなかった(EC50>100μg/mL、-)。MT-2細胞に対しては、10の抽出物が中等度の阻害活性、48の抽出物が弱い阻害活性を示し、残りは活性を示さなかった。Annona reticulataとA. squamosaの地上部の抽出物は阻害活性が最も強力で、それら抽出物から活性成分として、3つのアポルフィンアルカロイドが分離された。

石井文規, 山内靖, 乗富智明, 石塚賢治, 林博之, 鍋島一樹, 山下裕一 . von Willebrand病患者に発生した肝細胞癌の1切除例 . 日本消化器外科学会雑誌46 ( 10 ) 791 - 797 2013.10von Willebrand病患者に発生した肝細胞癌の1切除例

Publisher：(一社)日本消化器外科学会

症例は59歳の女性で,幼少時より鼻出血を繰り返し,数回の赤血球輸血を受けていた.9年前より慢性C型肝炎を指摘され近医で経過観察されていた.今回,肝S6に径4cm大の腫瘍を指摘され当科紹介となった.家族歴と血液検査結果よりvon Willebrand病(von Willebrand disease;以下,vWDと略記)患者に発生した肝細胞癌と診断した.凝固因子補充療法のガイドラインに従い,activated partial thromboplastin time(APTT)を指標として血液凝固第VIII因子(blood clotting factor VIII;以下,F VIIIと略記)製剤の投与後に肝部分切除術を施行した.術後第1病日より8日間のF VIII製剤の補充を行い,術後経過良好にて第13病日に退院となった.vWD病患者においてもF VIII製剤の補充を行うことで安全に肝切除を施行した症例を報告する.(著者抄録)

Nakano D. . Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (III) . Journal of Natural Medicines67 ( 4 ) 894 - 903 2013.10

Nakano D. . Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma (II): Apoptosis of antiproliferactive principle (24,25-dihydrowithanolide D) against ATL cell lines and structure-activity relationships with withanolides isolated from solanaceous plants . Journal of Natural Medicines67 ( 2 ) 415 - 420 2013.4

Nakano Daisuke, Ishitsuka Kenji, Katsuya Hiroo, Kunami Naoko, Nogami Rumiko, Yoshimura Yuka, Matsuda Michika, Kamikawa Mio, Tsuchihashi Ryota, Okawa Masafumi, Ikeda Tsuyoshi, Nohara Toshihiro, Tamura Kazuo, Kinjo Junei . ヒト成人T細胞白血病/リンパ腫(II)に対する植物由来の化学療法の候補のスクリーニング　ナス科の植物から単離したウィタノリドの抗増殖活性成分(24,25-ジヒドロウィタノリドD)によるATL細胞株のアポトーシスと構造活性相関(Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma: apoptosis of antiproliferactive principle (24,25-dihydrowithanolide D) against ATL cell lines and structure-activity relationships with withanolides isolated from solanaceous plants) . Journal of Natural Medicines67 ( 2 ) 415 - 420 2013.4ヒト成人T細胞白血病/リンパ腫(II)に対する植物由来の化学療法の候補のスクリーニング　ナス科の植物から単離したウィタノリドの抗増殖活性成分(24,25-ジヒドロウィタノリドD)によるATL細胞株のアポトーシスと構造活性相関(Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukemia/lymphoma: apoptosis of antiproliferactive principle (24,25-dihydrowithanolide D) against ATL cell lines and structure-activity relationships with withanolides isolated from solanaceous plants)

Publisher：シュプリンガー・ジャパン(株)

著者等は以前に、162種の植物からの214種の抽出物について、ヒト成人T細胞白血病/リンパ腫(ATL)細胞株に対する抗増殖成分のスクリーニングを行い、数種のウィタノリドを単離し、その構造活性相関(SAR)について検討した。今回更にSARについての研究範囲を広げて、ナス科の植物から既に単離していた31種のウィタノリドを用いてATL細胞株に対する抗増殖活性を調べた。活性発現には、5β、6β-エポキシ基と共に4β-ヒドロキシ基が必須であると推測された。3-と27-位のどちらかの位置の糖の存在により、逆に活性が低下した。更に24,25-ジヒドロウィタノリドDが最も強い阻害物質であり、アポトーシス性細胞死を誘導してATL細胞株に対する選択毒性を示すことが示された。

Ishii Fuminori, Yamauchi Yasushi, Noritomi Tomoaki, Ishitsuka Kenji, Hayashi Hiroyuki, Nabeshima Kazuki, Yamashita Yuichi . Hepatectomy in a Patient with von Willebrand Disease under Supplementation of Factor VIII Concentrate: A Case Report . The Japanese Journal of Gastroenterological Surgery46 ( 10 ) 791 - 797 2013

Publisher：The Japanese Society of Gastroenterological Surgery

A 59-year-old woman was referred to our hospital for treatment of a hepatic mass. She had a history of repeated nosebleeds at a young age, and had received blood transfusions several times. She had been given a diagnosis of chronic hepatitis C by a local physician 9 years previously. On admission, the activated partial thromboplastin time (APTT) was slightly prolonged, and the bleeding time was prolonged. On further examination, the von Willebrand factor (<6%) and factor VIII (52%) levels were found to be decreasing. Hepatocellular carcinoma was diagnosed, and her bleeding tendency was thought to be due to von Willebrand disease. According to the guidelines for coagulation factor replacement therapy, using the APTT as an index, we administered blood clotting factor VIII/von Willebrand factor concentrate for 8 days before and after surgery, and successfully maintained the APTT. The patient's postoperative course was uneventful. In this case, we successfully and safely performed hepatectomy in a patient with von Willebrand disease by supplying factor VIII/von Willebrand factor concentrate.

DOI： 10.5833/jjgs.2012.0320

Scopus

ISHITSUKA Kenji, UCHINO Junji, KATO Junko, IKUTA Mikihiro, WATANABE Kentaro, MATSUNAGA Akira, TAMURA Kazuo . First reported case of hemoglobin lansing in Asia detected by false low oxygen saturation on pulse oximetry . International journal of hematology95 ( 6 ) 731 - 732 2012.6

Katsuya H. . Prognostic index for acute- and lymphoma-type adult T-cell leukemia/lymphoma . Journal of Clinical Oncology30 ( 14 ) 1635 - 1640 2012.5

Ishitsuka K. . Targeting Bcl-2 family proteins in adult T-cell leukemia/lymphoma: In vitro and in vivo effects of the novel Bcl-2 family inhibitor ABT-737 . Cancer Letters317 ( 2 ) 218 - 225 2012.4

Ishida T. . Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: A multicenter phase II study . Journal of Clinical Oncology30 ( 8 ) 837 - 842 2012.3

Arimura K. . PDGF receptor β signaling in pericytes following ischemic brain injury . Current Neurovascular Research9 ( 1 ) 1 - 9 2012.2

Ishitsuka K. . Interferon alfa and antiretroviral agents: A treatment option for adult T-cell leukemia/lymphoma . Drugs of Today47 ( 8 ) 615 - 623 2011.8

Nakano Daisuke, Ishitsuka Kenji, Hatsuse Takahiro, TSUCHIHASHI Ryota, OKAWA Masafumi, OKABE Hikaru, TAMURA Kazuo, KINJO Junei . Screening of promising chemotherapeutic candidates against human adult T-cell leukemia/lymphoma from plants : active principles from Physalis pruinosa and structure-activity relationships with withanolides . Journal of natural medicines65 ( 3 ) 559 - 567 2011.7

Kunami N. . Antitumor effects of CRM197, a specific inhibitor of HB-EGF, in T-cell acute lymphoblastic leukemia . Anticancer Research31 ( 7 ) 2483 - 2488 2011.7

Nakano D. . Screening of promising chemotherapeutic candidates against human adult T-cell leukemia/lymphoma from plants: Active principles from Physalis pruinosa and structure-activity relationships with withanolides . Journal of Natural Medicines65 ( 3-4 ) 559 - 567 2011.7

Nakano Daisuke, Ishitsuka Kenji, Hatsuse Takahiro, Tsuchihashi Ryota, Okawa Masafumi, Okabe Hikaru, Tamura Kazuo, Kinjo Junei . ATLに対する化学療法薬の探索研究:ショクヨウホオズキに含まれる活性成分(withanolides)と構造活性相関について(Screening of promising chemotherapeutic candidates against human adult T-cell leukemia/lymphoma from plants: active principles from Physalis pruinosa and structure-activity relationships with withanolides) . Journal of Natural Medicines65 ( 3-4 ) 559 - 567 2011.7ATLに対する化学療法薬の探索研究:ショクヨウホオズキに含まれる活性成分(withanolides)と構造活性相関について(Screening of promising chemotherapeutic candidates against human adult T-cell leukemia/lymphoma from plants: active principles from Physalis pruinosa and structure-activity relationships with withanolides)

Publisher：シュプリンガー・ジャパン(株)

ATL(adult T-cell leukemia)はHTLV-1により引き起こされる疾患で,急性期に有効な治療法は存在しない.新たな化学療法薬探索の目的で,抗ATL活性を指標に162種214個の植物エキスライブラリーのスクリーニングを行い,ショクヨウホオズキ地上部エキスが顕著な活性を示すことを明らかとした.生物活性を指標に分離精製を行った結果,5種のwithanolidesを得た.また,活性測定の結果,B環にエポキシ基をもつ化合物が最も強い活性を示すことを明らかにするとともに,正常細胞に対する選択的毒性があることも明らかとした.(著者抄録)

Kunami N, Yotsumoto F, Ishitsuka K, Fukami T, Odawara T, Manabe S, Ishikawa T, Tamura K, Kuroki M, Miyamoto S . Antitumor effects of CRM197, a specific inhibitor of HB-EGF, in T-cell acute lymphoblastic leukemia. . Anticancer research31 ( 7 ) 2483 - 8 2011.7Antitumor effects of CRM197, a specific inhibitor of HB-EGF, in T-cell acute lymphoblastic leukemia.

ISHITSUKA Kenji, KATSUYA Hiroo, TOYOTA Tomona, ISHIZU Masanao, KUNAMI Naoko, FUJITA Mana, SASAKI Hidenori, TAKAMATSU Yasushi, UCHIYAMA Masanobu, FUJIKANE Haruo, OGATA Kentaro, HARA Shuuji, TAMURA Kazuo . Interferon-α and zidovudine for relapsed/refractory adult T cell leukemia/lymphoma : case reports of Japanese patients . International journal of hematology92 ( 5 ) 762 - 764 2010.12

Ishitsuka K. . Interferon-α and zidovudine for relapsed/refractory adult T cell leukemia/lymphoma: Case reports of Japanese patients . International Journal of Hematology92 ( 5 ) 762 - 764 2010.12

Ishitsuka Kenji, Katsuya Hiroo, Toyota Tomona, Ishizu Masanao, Kunami Naoko, Fujita Mana, Sasaki Hidenori, Takamatsu Yasushi, Uchiyama Masanobu, Fujikane Haruo, Ogata Kentaro, Hara Shuuji, Tamura Kazuo . 再発/難治性成人T細胞白血病/リンパ腫に対するインターフェロン-αとジドブジン　日本人患者の症例報告(Interferon-α and zidovudine for relapsed/refractory adult T cell leukemia/lymphoma: case reports of Japanese patients) . International Journal of Hematology92 ( 5 ) 762 - 764 2010.12再発/難治性成人T細胞白血病/リンパ腫に対するインターフェロン-αとジドブジン　日本人患者の症例報告(Interferon-α and zidovudine for relapsed/refractory adult T cell leukemia/lymphoma: case reports of Japanese patients)

Publisher：(一社)日本血液学会

インターフェロン-αとジドブジン(IFN/AZT)の日本での評価はまだなされていない。IFN/AZTを成人T細胞白血病/リンパ腫(ATL)の3症例(63歳男性、62歳女性、48歳男性)に用いた。63歳男性は修正EPOCH療法で完全緩解を得たが、斑状皮膚病巣からATL細胞浸潤が認められIFN/AZTを開始し、急速に皮膚症状が消え1ヵ月以内にWBCが減少した。62歳女性は無治療で4年間くすぶっていたATLが発症し、THP-COPで治療し部分緩解となった。2ヵ月後病状が悪化しINF/AZTを開始した。反応は明確ではなかったが、病状は抑えることができた。48歳男性は急性ATLと診断されCHOPとVCAP、AMP、VECPで治療したが効果はなく、この処方は重篤な骨髄抑制を示した。IFN/AZTを開始したが、効果は見られず22日間で中止した。同種幹細胞移植に備えての骨髄機能を廃絶する処方でもATL症状を根絶することはできなかった。

Shiraishi Takeshi, Hiratsuka Masafumi, Higuchi Takao, Yanagisawa Jun, Miyahara Sou, Imakiire Naoyuki, Nakashima Hiroyasu, Hamanaka Wakako, Hagio Yasuko, Hamatake Daisuke, Obuchi Toshiro, Yoshinaga Yasuteru, Oka Yoichirou, Nakamura Masatoshi, Masumoto Kouji, Shirakusa Takayuki, Iwasaki Akinori, Yamauchi Yasushi, Hoshino Seiichiro, Noritomi Tomoaki, Yamashita Yuichi, Shiraishi Motokimi, Fujita Masaki, Watanabe Kentaro, Morishige Noritugu, Tashiro Tadashi, Sako Hideto, Nishikawa Hiroaki, Saku Keijiro, Ishituka Kenji, Takamatsu Yasushi, Tamura Kazuo, Shigematsu Kenji, Higa Kazuo, Ogomori Kouji, Nishimura Ryouji, Nabeshima Kazuki, Yoshimura Yukari, Shiota Etsuji, Ueyama Miho, Takaishi Manami . First registry report of the Fukuoka University lung transplantation program 2005-2010 . Medical bulletin of Fukuoka University37 ( 3 ) 133 - 142 2010.9

KUNAMI Naoko, TAKAMATSU Yasushi, FUJITA Mana, KATSUYA Hiroo, SASAKI Hidenori, WAKAMATSU Shinichi, ISHITSUKA Kenji, NABESHIMA Kazuki, TAMURA Kazuo . Extranodal NK/T-cell lymphoma arising from soft tissue of the left forearm . The Japanese journal of clinical hematology51 ( 6 ) 422 - 426 2010.6

Kunami N, Takamatsu Y, Fujita M, Katsuya H, Sasaki H, Wakamatsu S, Ishitsuka K, Nabeshima K, Tamura K . [Extranodal NK/T-cell lymphoma arising from soft tissue of the left forearm]. . [Rinsho ketsueki] The Japanese journal of clinical hematology51 ( 6 ) 422 - 6 2010.6[Extranodal NK/T-cell lymphoma arising from soft tissue of the left forearm].

工並直子, 高松泰, 藤田愛, 勝屋弘雄, 佐々木秀法, 若松信一, 石塚賢治, 鍋島一樹, 田村和夫 . 前腕軟部組織に生じた節外性NK/T細胞リンパ腫 . 臨床血液51 ( 6 ) 422 - 426 2010.6前腕軟部組織に生じた節外性NK/T細胞リンパ腫

Publisher：(一社)日本血液学会-東京事務局

72歳男性。左前腕部に腫脹を生じ蜂窩織炎の診断で抗菌剤治療を受けたが改善しなかった。7ヵ月後に疼痛,発熱を伴い腫脹が増大したため病巣掻爬術と抗菌剤含有セメント挿入術を施行された。2ヵ月後にさらに腫脹が増大したため組織検査を再検し,壊死組織とその辺縁に中型異型リンパ球の増殖を認めた。異型リンパ球はCD3,CD56,CD30,TIA1,granzymeB,EBERが陽性,CD4,CD8,CD25,CD79a,CD20が陰性で節外性NK/T細胞リンパ腫(ENKL)と診断,臨床病期はIIB期だった。左前腕腫瘤の放射線療法と多剤併用化学療法を行い病変は縮小したが,掻爬部の壊死と腐敗が進行し左上肢を切断した。現在まで約2年無増悪生存している。治療に反応しない蜂窩織炎様病変の鑑別診断にはENKLも考慮し,適切な診断と治療を行うことが肝要である。(著者抄録)

Kunami N. . Extranodal NK/T-cell lymphoma arising from soft tissue of the left forearm . [Rinshō ketsueki] The Japanese journal of clinical hematology51 ( 6 ) 422 - 426 2010.6

津川潤, 坪井義夫, 井上展聡, 石塚賢治, 竹下盛重, 山田達夫 . 円錐上部症候群で発症し骨髄生検により診断した血管内リンパ腫の1例 . BRAIN and NERVE: 神経研究の進歩62 ( 3 ) 269 - 272 2010.3円錐上部症候群で発症し骨髄生検により診断した血管内リンパ腫の1例

Publisher：(株)医学書院

症例は46歳女性で、右足底部の異常感覚(ジンジン感)が出現し、右下腿、大腿後面と広がった。その後、しびれ感が出現し、下肢脱力のためバスの乗り降りなどが困難となり尿意を感じなくなった。意識清明、脳神経に異常を認めず、両下肢遠位筋は軽度の筋力低下を認めた。右大腿・下腿後面、両足底部および臀部に表在覚低下と異常感覚を認めた。深部腱反射右膝蓋腱反射が低下し、両アキレス腱反射が消失し、病的反射は認めなかった。責任病巣は下位腰髄から円錐上部と推測されるもの画像所見から異常を認めず、骨髄穿刺で血管内リンパ腫(IVL)と診断した。円錐上部症候群で発症したIVLで、亜急性進行性で原因不明の下位腰髄・円錐上部障害や上行性脊髄症をみた場合、IVLの可能性を考えることが重要と思われた。

Publisher：The Japanese Society of Hematology

A 72-year-old man with extranodal natural killer cell lymphoma (ENKL) presented with a painless swelling of the left forearm. He was initially diagnosed as having a bacterial cellulitis and received antimicrobial therapy. However, his left arm became increasingly swollen in association with fever and redness of the lesion. Therefore, he underwent focal dissection. Because of persistent swelling, the left arm was rebiopsied 9 months later, and a diagnosis of ENKL developing in the subcutis was established. He was treated with focal radiation therapy in combination with dexamethasone, etoposide, ifosfamide, methotrexate and L-asparaginase. The lesion was significantly reduced in size but did not disappear completely. Two months later the lesion became necrotic, although swelling of the forearm lesion, left axillary and cervical lymph nodes were kept under control. We then performed amputation of the left forearm since it could not be saved medically. The patient currently remains alive and well without progression 2 years after amputation. When evaluating panniculitis, which is difficult to cure, ENKL should be considered in the differential diagnosis and treated appropriately.

DOI： 10.11406/rinketsu.51.422

TAKAMATSU Yasushi, SUZUMIYA Junji, OGATA Kentaro, KATAYOSE Keiko, SASAKI Hidenori, ISHITSUKA Kenji, KIMURA Nobuhiro, TAMURA Kazuo . Cladribine Treatment in Two-Hour Intravenous Infusion for Previously-Treated Low Grade B-Cell Lymphoma : A Pilot Study . Journal of clinical and experimental hematopathology49 ( 2 ) 69 - 75 2009.11

Publisher：日本リンパ網内系学会

Cladribine is approved to be used in 24-hour continuous infusion for the treatment of low-grade lymphoma by the Ministry of Health, Labor and Welfare in Japan. Pharmacokinetic studies showed that the antitumor activity of cladribine by 2-hour infusion should be comparable to that given by continuous infusion. The safety and anti-tumor activity of short infusion of cladribine was shown in hairy cell leukemia, chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphoma in Europe. We therefore underwent a pilot study to confirm the safety and efficacy of cladribine given by 2-hour infusion for Japanese patients with relapsed or refractory indolent B-cell lymphoma. Cladribine at a dose of 0.09 mg/kg was administered in 2-hour intravenous infusion for 5 consecutive days. The treatment was repeated at a 28-day interval for at least 2 cycles, and its efficacy and toxicity were investigated. Fourteen patients were entered into this study. Eight patients (57%) responded to cladribine, including 2 (14%) complete response (CR) and 6 (43%) partial response (PR). The median duration of response was 20+ and 21+ months for CR, and 12 months ranging from 3 to 34 months for PR, respectively. Grade 3 or 4 neutropenia and lymphocytopenia occurred in 43% and 71% of patients, respectively, but there was no febrile neutropenia or opportunistic infection associated with cladribine treatment. No other adverse events greater than grade 3 were encountered. The tumor response and degree of toxicity were comparable with those observed in cladribine treatment given by continuous infusion at a same dose. Cladribine can be administered in 2-hour infusion in an outpatient clinic and is therefore quite convenient for patients. [J Clin Exp Hematopathol 49(2) : 69-75, 2009]

DOI： 10.3960/jslrt.49.69

Scopus

PubMed

Takamatsu Yasushi, Suzumiya Junji, Ogata Kentaro, Katayose Keiko, Sasaki Hidenori, Ishitsuka Kenji, Kimura Nobuhiro, Tamura Kazuo . 以前に治療を受けた低悪性度B細胞リンパ腫に対する2時間のクラドリビン静脈内注入による治療　試験的研究(Cladribine Treatment in Two-Hour Intravenous Infusion for Previously-Treated Low Grade B-Cell Lymphoma: A Pilot Study) . Journal of Clinical and Experimental Hematopathology49 ( 2 ) 69 - 75 2009.11以前に治療を受けた低悪性度B細胞リンパ腫に対する2時間のクラドリビン静脈内注入による治療　試験的研究(Cladribine Treatment in Two-Hour Intravenous Infusion for Previously-Treated Low Grade B-Cell Lymphoma: A Pilot Study)

Publisher：(一社)日本リンパ網内系学会

再発性および難治性の緩慢性B細胞リンパ腫の日本人患者に対して、クラドリビンを2時間静脈内注入し、安全性と有効性を調べる試験的研究を行った。14名の患者を対象として0.09mg/kgのクラドリビンの静脈内注入を1日2時間、5日間行った。投与は28日間隔で最低2サイクル行い、有効性と毒性を評価した。クラドリビン投与に対し2名は完全緩解(CR)、6名は部分緩解(PR)を達成した。反応継続期間はCRで20+と21+ヶ月、PRで3〜34ヵ月であった。第3〜4度の好中球減少とリンパ球減少がそれぞれ43%、71%の患者で生じた。発熱性好中球減少や、クラドリビン投与に関連した日和見感染はみられなかった。第3度以上の有害事象は生じなかった。腫瘍反応と毒性の程度はクラドリビンを持続注入した際と同程度であった。クラドリビン治療は外来診察室での2時間の静脈内注入で行うことが可能である。

Katsuya H. . Addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy has a high risk of developing interstitial pneumonia in patients with non-Hodgkin lymphoma . Leukemia and Lymphoma50 ( 11 ) 1818 - 1823 2009.11

KATSUYA Hiroo, TAKATA Tohru, ISHIKAWA Takahiko, SASAKI Hidenori, ISHITSUKA Kenji, TAKAMATSU Yasushi, TAMURA Kazuo . A patient with acute myeloid leukemia who developed fatal pneumonia caused by carbapenem-resistant Bacillus cereus . Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy15 ( 1 ) 39 - 41 2009.2

Katsuya H. . A patient with acute myeloid leukemia who developed fatal pneumonia caused by carbapenem-resistant Bacillus cereus . Journal of Infection and Chemotherapy15 ( 1 ) 39 - 41 2009.2

Katsuya Hiroo, Takata Tohru, Ishikawa Takahiko, Sasaki Hidenori, Ishitsuka Kenji, Takamatsu Yasushi, Tamura Kazuo . カルバペネム耐性セレウス菌を原因とする致死性肺炎を発症した急性骨髄性白血病患者(A patient with acute myeloid leukemia who developed fatal pneumonia caused by carbapenem-resistant Bacillus cereus) . Journal of Infection and Chemotherapy15 ( 1 ) 39 - 41 2009.2カルバペネム耐性セレウス菌を原因とする致死性肺炎を発症した急性骨髄性白血病患者(A patient with acute myeloid leukemia who developed fatal pneumonia caused by carbapenem-resistant Bacillus cereus)

Publisher：エルゼビア・ジャパン(株)

症例は末梢血に芽細胞を認めた60歳の男性で、急性骨髄性白血病と診断された。入院9日目に白血球減少状態となり、14日目に発熱を認めたため、セフェピムの投与を開始した。24日目に再びスパイク熱を発症したことから、セフェピムからパニペネム/ベタミプロンに切り替えた。28日後に咳嗽、左側胸膜痛及び下痢を認めたため、翌日CT検査を行ったところ、左側肺全体に広がる融合性の浸潤物を認め、同日死亡した。血液及び喀痰からセレウス菌が検出された。抗生物質感受性試験を行ったところ、セフェピムのみならずパニペネム/ベタミプロンに耐性を示した。本症例は好中球減少症患者におけるカルバペネム耐性セレウス菌を原因とする劇症型感染症の最初の症例である。好中球減少症患者が肺炎を発症した際にはセレウス菌感染を念頭に置くべきである。

Suzuki S. . Aggressive NK cell leukaemia after splenectomy: Association with CD95-resistant memory T-cell proliferation and recalcitrant clinical course of haemophagocytic syndrome . European Journal of Haematology81 ( 3 ) 236 - 241 2008.9

Ishitsuka K. . p38 mitogen-activated protein kinase inhibitor LY2228820 enhances bortezomib-induced cytotoxicity and inhibits osteoclastogenesis in multiple myeloma; therapeutic implications . British Journal of Haematology141 ( 5 ) 598 - 606 2008.6

Ishitsuka K. . Treatment of adult T-cell leukemia/lymphoma: Past, present, and future . European Journal of Haematology80 ( 3 ) 185 - 196 2008.3

KATSUYA Hiroo, ISHITSUKA Kenji, SASAKI Hidenori, WAKAMATSU Shinichi, TAKAMATSU Yasushi, SUZUMIYA Junji, TAMURA Kazuo, INOUE Hirosato, TSUBOI Yoshio . Hypersomnia as a presentation of paraneoplastic limbic encephalitis in a patient with adult T cell leukemia/lymphoma . Nihon Naika Gakkai Zasshi97 ( 2 ) 410 - 412 2008.2

勝屋弘雄, 石塚賢治, 佐々木秀法, 若松信一, 高松泰, 鈴宮淳司, 田村和夫, 井上展聡, 坪井義夫 . 傍腫瘍性辺縁系脳炎による突発性睡眠を発症した急性型成人T細胞白血病の1例 . 日本内科学会雑誌97 ( 2 ) 410 - 412 2008.2傍腫瘍性辺縁系脳炎による突発性睡眠を発症した急性型成人T細胞白血病の1例

Publisher：(一社)日本内科学会

58歳女。右頸部腫瘤と全身倦怠感、その後に傾眠傾向が出現し近医受診したところ、頸部リンパ節腫大の指摘で紹介入院となった。会話を止めると2、3秒で眠る状態で、扁桃生検よりMalignant lymphoma、diffuse、pleomorphic、T-cell typeと判断した。MRI、FLAIR像では両側扁桃体、海馬、海馬傍回、視床下部、尾状核頭部で高信号を呈していた。以上の検査結果から、急性型成人T細胞白血病(ATLL)と診断した。また、突発性睡眠は傍腫瘍性辺縁系脳炎(PLE)と考えた。ATLLに対しLSG15プロトコールによる化学療法を行ったところ、右頸部リンパ節、右扁桃腺は縮小し、突発性睡眠も消失、異常所見もほぼ消失した。

KAWAMOTO Kenichiro, TAKESHITA Morishige, IWASAKI Hiroshi, ISHITSUKA Kenji, TSUNODA Kazuyuki, TSUNODA Yuichi . Extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALToma) of prostate ; a case report . 25 ( 1 ) 43 - 46 2008.1

川本研一郎, 竹下盛重, 岩崎宏, 石塚賢治, 角田和之, 角田雄一 . 前立腺に発生したMALTリンパ腫の1例 . 診断病理25 ( 1 ) 43 - 46 2008.1前立腺に発生したMALTリンパ腫の1例

Publisher：(一社)日本病理学会

症例は70歳男性。尿閉を主訴に来院した。直腸診で、前立腺はやや弾性硬で中等度に肥大しており、prostate specific antigen(PSA)は10.4ng/mlと高値を示した。前立腺癌を疑い経直腸的生検と経尿道的切除術(TUR-P)を行った。組織学的には生検、TUR-Pともに小型から中型のcentrocyte-like cells(CCL細胞)の間質へのびまん性浸潤がみられ、上皮内にリンパ球が浸潤したlymphoepithelial lesion(LEL)がみられた。浸潤しているCCL細胞はCD20,CD79a陽性であったが、IgGκ,λに偏りはなく形質細胞分化はみられなかった。MIB-1陽性率は約20%であった。CT検査にて、前立腺以外の臓器に病変は認められなかった。前立腺原発の節外性粘膜関連濾胞辺縁帯リンパ腫(MALTリンパ腫)は報告が少なく、まれな症例と考えた。(著者抄録)

緒方憲太郎, 内山将伸, 石塚賢治, 二神幸次郎 . 20-P1-109 イマチニブによる用量依存性発熱を克服した1例(有害事象・副作用,来るべき時代への道を拓く) . 日本医療薬学会年会講演要旨集18 ( 0 ) 2008

Vallet S, Raje N, Ishitsuka K, Hideshima T, Podar K, Chhetri S, Pozzi S, Breitkreutz I, Kiziltepe T, Yasui H, Ocio EM, Shiraishi N, Jin J, Okawa Y, Ikeda H, Mukherjee S, Vaghela N, Cirstea D, Ladetto M, Boccadoro M, Anderson KC . MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts. . Blood110 ( 10 ) 3744 - 52 2007.11MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts.

Kiziltepe T, Hideshima T, Ishitsuka K, Ocio EM, Raje N, Catley L, Li CQ, Trudel LJ, Yasui H, Vallet S, Kutok JL, Chauhan D, Mitsiades CS, Saavedra JE, Wogan GN, Keefer LK, Shami PJ, Anderson KC . JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells. . Blood110 ( 2 ) 709 - 18 2007.7JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells.

Kiziltepe T, Hideshima T, Catley L, Raje N, Yasui H, Shiraishi N, Okawa Y, Ikeda H, Vallet S, Pozzi S, Ishitsuka K, Ocio EM, Chauhan D, Anderson KC . 5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicin and bortezomib against multiple myeloma cells. . Molecular cancer therapeutics6 ( 6 ) 1718 - 27 2007.65-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicin and bortezomib against multiple myeloma cells.

Ishitsuka K. . Therapeutic potential of arsenic trioxide with or without interferon-α for relapsed/refractory adult T-cell leukemia/lymphoma . Haematologica92 ( 5 ) 719 - 720 2007.5

Yasui H, Hideshima T, Ikeda H, Jin J, Ocio EM, Kiziltepe T, Okawa Y, Vallet S, Podar K, Ishitsuka K, Richardson PG, Pargellis C, Moss N, Raje N, Anderson KC . BIRB 796 enhances cytotoxicity triggered by bortezomib, heat shock protein (Hsp) 90 inhibitor, and dexamethasone via inhibition of p38 mitogen-activated protein kinase/Hsp27 pathway in multiple myeloma cell lines and inhibits paracrine tumour growth. . British journal of haematology136 ( 3 ) 414 - 23 2007.2BIRB 796 enhances cytotoxicity triggered by bortezomib, heat shock protein (Hsp) 90 inhibitor, and dexamethasone via inhibition of p38 mitogen-activated protein kinase/Hsp27 pathway in multiple myeloma cell lines and inhibits paracrine tumour growth.

Podar K, Tonon G, Sattler M, Tai YT, Legouill S, Yasui H, Ishitsuka K, Kumar S, Kumar R, Pandite LN, Hideshima T, Chauhan D, Anderson KC . The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma. . Proceedings of the National Academy of Sciences of the United States of America103 ( 51 ) 19478 - 83 2006.12The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma.

Hideshima T, Neri P, Tassone P, Yasui H, Ishitsuka K, Raje N, Chauhan D, Podar K, Mitsiades C, Dang L, Munshi N, Richardson P, Schenkein D, Anderson KC . MLN120B, a novel IkappaB kinase beta inhibitor, blocks multiple myeloma cell growth in vitro and in vivo. . Clinical cancer research : an official journal of the American Association for Cancer Research12 ( 19 ) 5887 - 94 2006.10MLN120B, a novel IkappaB kinase beta inhibitor, blocks multiple myeloma cell growth in vitro and in vivo.

Neri P, Yasui H, Hideshima T, Tassone P, Raje N, Catley LP, Ishitsuka K, Blotta S, Kiziltepe T, Ocio EM, Fulciniti M, Kanekal S, Elliott GT, Munshi NC, Anderson KC . In vivo and in vitro cytotoxicity of R-etodolac with dexamethasone in glucocorticoid-resistant multiple myeloma cells. . British journal of haematology134 ( 1 ) 37 - 44 2006.7In vivo and in vitro cytotoxicity of R-etodolac with dexamethasone in glucocorticoid-resistant multiple myeloma cells.

Hideshima T, Catley L, Yasui H, Ishitsuka K, Raje N, Mitsiades C, Podar K, Munshi NC, Chauhan D, Richardson PG, Anderson KC . Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells. . Blood107 ( 10 ) 4053 - 62 2006.5Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells.

Kumar S, Raje N, Hideshima T, Ishitsuka K, Podar K, Le Gouille S, Chauhan D, Richardson P, Munshi NC, Anderson K . FQPD, a novel immunomodulatory drug, has significant in vitro activity in multiple myeloma. . British journal of haematology132 ( 6 ) 698 - 704 2006.3FQPD, a novel immunomodulatory drug, has significant in vitro activity in multiple myeloma.

Roccaro AM, Hideshima T, Raje N, Kumar S, Ishitsuka K, Yasui H, Shiraishi N, Ribatti D, Nico B, Vacca A, Dammacco F, Richardson PG, Anderson KC . Bortezomib mediates antiangiogenesis in multiple myeloma via direct and indirect effects on endothelial cells. . Cancer research66 ( 1 ) 184 - 91 2006.1Bortezomib mediates antiangiogenesis in multiple myeloma via direct and indirect effects on endothelial cells.

Ishitsuka K, Hideshima T, Hamasaki M, Raje N, Kumar S, Hideshima H, Shiraishi N, Yasui H, Roccaro AM, Richardson P, Podar K, Le Gouill S, Chauhan D, Tamura K, Arbiser J, Anderson KC . Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis. . Blood106 ( 5 ) 1794 - 800 2005.9Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis.

Ishitsuka K. . Novel inosine monophosphate dehydrogenase inhibitor VX-944 induces apoptosis in multiple myeloma cells primarily via caspase-independent AIF/Endo G pathway . Oncogene24 ( 38 ) 5888 - 5896 2005.9

Yasui H, Hideshima T, Raje N, Roccaro AM, Shiraishi N, Kumar S, Hamasaki M, Ishitsuka K, Tai YT, Podar K, Catley L, Mitsiades CS, Richardson PG, Albert R, Brinkmann V, Chauhan D, Anderson KC . FTY720 induces apoptosis in multiple myeloma cells and overcomes drug resistance. . Cancer research65 ( 16 ) 7478 - 84 2005.8FTY720 induces apoptosis in multiple myeloma cells and overcomes drug resistance.

Raje N, Kumar S, Hideshima T, Roccaro A, Ishitsuka K, Yasui H, Shiraishi N, Chauhan D, Munshi NC, Green SR, Anderson KC . Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma. . Blood106 ( 3 ) 1042 - 7 2005.8Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma.

Yasui H, Hideshima T, Hamasaki M, Roccaro AM, Shiraishi N, Kumar S, Tassone P, Ishitsuka K, Raje N, Tai YT, Podar K, Chauhan D, Leoni LM, Kanekal S, Elliott G, Munshi NC, Anderson KC . SDX-101, the R-enantiomer of etodolac, induces cytotoxicity, overcomes drug resistance, and enhances the activity of dexamethasone in multiple myeloma. . Blood106 ( 2 ) 706 - 12 2005.7SDX-101, the R-enantiomer of etodolac, induces cytotoxicity, overcomes drug resistance, and enhances the activity of dexamethasone in multiple myeloma.

Hamasaki M, Hideshima T, Tassone P, Neri P, Ishitsuka K, Yasui H, Shiraishi N, Raje N, Kumar S, Picker DH, Jacob GS, Richardson PG, Munshi NC, Anderson KC . Azaspirane (N-N-diethyl-8,8-dipropyl-2-azaspiro [4.5] decane-2-propanamine) inhibits human multiple myeloma cell growth in the bone marrow milieu in vitro and in vivo. . Blood105 ( 11 ) 4470 - 6 2005.6Azaspirane (N-N-diethyl-8,8-dipropyl-2-azaspiro [4.5] decane-2-propanamine) inhibits human multiple myeloma cell growth in the bone marrow milieu in vitro and in vivo.

Hideshima T, Chauhan D, Ishitsuka K, Yasui H, Raje N, Kumar S, Podar K, Mitsiades C, Hideshima H, Bonham L, Munshi NC, Richardson PG, Singer JW, Anderson KC . Molecular characterization of PS-341 (bortezomib) resistance: implications for overcoming resistance using lysophosphatidic acid acyltransferase (LPAAT)-beta inhibitors. . Oncogene24 ( 19 ) 3121 - 9 2005.4Molecular characterization of PS-341 (bortezomib) resistance: implications for overcoming resistance using lysophosphatidic acid acyltransferase (LPAAT)-beta inhibitors.

Raje N, Kumar S, Hideshima T, Ishitsuka K, Chauhan D, Mitsiades C, Podar K, Le Gouill S, Richardson P, Munshi NC, Stirling DI, Antin JH, Anderson KC . Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma. . Blood104 ( 13 ) 4188 - 93 2004.12Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma.

Hideshima T, Podar K, Chauhan D, Ishitsuka K, Mitsiades C, Tai YT, Hamasaki M, Raje N, Hideshima H, Schreiner G, Nguyen AN, Navas T, Munshi NC, Richardson PG, Higgins LS, Anderson KC . p38 MAPK inhibition enhances PS-341 (bortezomib)-induced cytotoxicity against multiple myeloma cells. . Oncogene23 ( 54 ) 8766 - 76 2004.11p38 MAPK inhibition enhances PS-341 (bortezomib)-induced cytotoxicity against multiple myeloma cells.

Hayashi T, Hideshima T, Nguyen AN, Munoz O, Podar K, Hamasaki M, Ishitsuka K, Yasui H, Richardson P, Chakravarty S, Murphy A, Chauhan D, Higgins LS, Anderson KC . Transforming growth factor beta receptor I kinase inhibitor down-regulates cytokine secretion and multiple myeloma cell growth in the bone marrow microenvironment. . Clinical cancer research : an official journal of the American Association for Cancer Research10 ( 22 ) 7540 - 6 2004.11Transforming growth factor beta receptor I kinase inhibitor down-regulates cytokine secretion and multiple myeloma cell growth in the bone marrow microenvironment.

Le Gouill S, Podar K, Amiot M, Hideshima T, Chauhan D, Ishitsuka K, Kumar S, Raje N, Richardson PG, Harousseau JL, Anderson KC . VEGF induces Mcl-1 up-regulation and protects multiple myeloma cells against apoptosis. . Blood104 ( 9 ) 2886 - 92 2004.11VEGF induces Mcl-1 up-regulation and protects multiple myeloma cells against apoptosis.

Podar K, Shringarpure R, Tai YT, Simoncini M, Sattler M, Ishitsuka K, Richardson PG, Hideshima T, Chauhan D, Anderson KC . Caveolin-1 is required for vascular endothelial growth factor-triggered multiple myeloma cell migration and is targeted by bortezomib. . Cancer research64 ( 20 ) 7500 - 6 2004.10Caveolin-1 is required for vascular endothelial growth factor-triggered multiple myeloma cell migration and is targeted by bortezomib.

YAMAUCHI Keita, IWAO Yasuhiro, OGATA Kentaro, HARA Shuuji, TAMURA Kazuo, SUZUMIYA Junji, ISHITSUKA Kenji, ONO Nobufumi . Pharmacokinetics of Arsenic Trioxide in Japanese patients with Acute Promyelocytic Leukemia and Adult T-Cell Leukemia Lymphoma . Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences)30 ( 7 ) 492 - 496 2004.7

Publisher：Japanese Society of Pharmaceutical Health Care and Sciences

Arsenic trioxide (As2O3) chemotherapy is now used for the treatment of relapsed patients with acute promyelocytic leukemia (APL) and adult T-cell leukemia (ATL) in the First Internal Medicine Department of Fukuoka University Hospital. In order to adjust the dosage, we studied the pharmacokinetics of As2O3 when administered intravenously to patients with APL and ATL. Plasma arsenic concentrations were measured by gas-chromatograph/mass-spectrometry (GC/MS). The maximum arsenic concentration (Cmax) and area under the curve (AUC) were 8.3±0.8 (μM) and 61.7±4.2 (μM·hr) on the first day and 8.6±0.7 (μM) and 63.5±6.6 (μM·hr) on the twentieth day of treatment, respectively. Apparent distribution volume and total body clearance were 0.14±0.02 (L/kg) (range 0.12-0.18) and 0.036±0.004 (L/hr/kg) (range 0.030-0.039), respectively. From these results, we conclude that the pharmacokinetic behavior of As2O3 did not alter in continuous administration, and the variation in pharmacokinetic parameters was extremely small among the patients.

DOI： 10.5649/jjphcs.30.492

山内惠太, 岩尾泰寛, 緒方憲太郎, 原周司, 田村和夫, 鈴宮淳司, 石塚賢治, 小野信文 . 急性前骨髄球性白血病および成人T細胞性白血病リンパ腫に対する亜ヒ酸療法施行時のヒ素の体内動態 . 医療薬学30 ( 7 ) 492 - 496 2004.7急性前骨髄球性白血病および成人T細胞性白血病リンパ腫に対する亜ヒ酸療法施行時のヒ素の体内動態

Publisher：(一社)日本医療薬学会

福岡大学倫理審査委員会の承認を得て,第一内科で実施した再発・治療抵抗性造血器腫瘍患者に対する亜ヒ酸療法施行時の体内動態について検討を行った.亜ヒ酸療法を目的として入院した急性前骨髄性白血病(APL)2例と成人T細胞性白血病リンパ腫(ATL)3例を対象とした.日内および日間変動係数(CV%)は2.1〜5.4%で,血清中からの回収率は95〜98%であった.定量限界(S/N)は0.05μMで,0.1-10μMの範囲内で良好な相関関係が得られた.血漿中ヒ素濃度は点滴静脈内投与終了時に最高値を示した後,速やかに低下し,24時間後にはほぼ投与前レベルに達した.連続投与によるヒ素体内動態の変動および血漿中におけるヒ素の蓄積性はほとんどないことが示唆された

Tai YT, Catley LP, Mitsiades CS, Burger R, Podar K, Shringpaure R, Hideshima T, Chauhan D, Hamasaki M, Ishitsuka K, Richardson P, Treon SP, Munshi NC, Anderson KC . Mechanisms by which SGN-40, a humanized anti-CD40 antibody, induces cytotoxicity in human multiple myeloma cells: clinical implications. . Cancer research64 ( 8 ) 2846 - 52 2004.4Mechanisms by which SGN-40, a humanized anti-CD40 antibody, induces cytotoxicity in human multiple myeloma cells: clinical implications.

Ishitsuka K. . Bone marrow necrosis in a patient with acute promyelocytic leukemia during re-induction therapy with arsenic trioxide . European Journal of Haematology72 ( 4 ) 280 - 284 2004.4

ISHITSUKA Kenji, IKEDA Syuichi, IZUMI Youichiro, IMAMURA Yutaka, UIKE Naokuni, UOZUMI Kimiharu, UTSUNOMIYA Atae, KAWANO Fumio, KUBUKI Youko, GONDO Hisashi, SABURI Yoshio, SIBUYA Tsunefumi, SUZUSIMA Jin, TSUKADA Jyunichi, HAYASHI Makoto, MAEDA Kouichi, MATUISHI Eijyo, MATSUOKA Hitoshi, MAKINO Sigeyoshi, TAMURA Kazuo . Infection control for the treatment of hematological malignancies:a survey of the Kyushu Hematology Organization for Treatment Study Group(K-HOT) . Rinsho Ketsueki44 ( 7 ) 483 - 490 2003.7

Publisher：The Japanese Society of Hematology

The Kyushu Hematology Organization for Treatment Study Group (K-HOT) consisted of 22 institutions specializing in hematology in Kyushu. This study is aimed at reviewing the daily practice of infection control for the treatment of hematological malignancies in our group. Nominal questionnaires were mailed to the hematology department in each institution from November 2001 to April 2002. For the first general surveys, 19 of 22 (86%) institutions responded. The second survey was mailed to the 19 respondents and 17 answered the detailed questionnaires with a response rate of 89%. Prophylactic use of trimethoprim-sulfamethoxazole (ST) against Pneumocystis carinii and anti-mycobacterial drugs in patients who had a history of tuberculosis was routine especially for patients with adult T-cell leukemia/lymphoma (ATL). Furthermore, the neutrophil counts to start a granulocyte-colony stimulating factor appeared to be high in ATL as compared with other hematological malignancies. In the setting of autologous stem cell transplantation (SCT), prophylactic use of acyclovir, immunoglobulin and ST was not routine and was reduced in duration, if used at all, as compared with allogeneic SCT. For allogeneic SCT, the cumulative dose of immunoglobulin significantly varied from institutions to institutions. The benefit of this study is the ability to recognize practical management patterns for infection control.

DOI： 10.11406/rinketsu.44.483

Ishitsuka K, Ikeda S, Izumi Y, Imamura Y, Uike N, Uozumi K, Utsunomiya A, Kawano F, Kubuki Y, Gondo H, Saburi Y, Sibuya T, Suzusima J, Tsukada J, Hayashi M, Maeda K, Matuishi E, Matsuoka H, Makino S, Tamura K . [Infection control for the treatment of hematological malignancies: a survey of the Kyushu Hematology Organization for Treatment Study Group (K-HOT)]. . [Rinsho ketsueki] The Japanese journal of clinical hematology44 ( 7 ) 483 - 90 2003.7[Infection control for the treatment of hematological malignancies: a survey of the Kyushu Hematology Organization for Treatment Study Group (K-HOT)].

石塚賢治, 池田柊一, 和泉洋一郎, 今村豊, 鵜池直邦, 魚住公治, 宇都宮與, 河野文夫, 久富木庸子, 権藤久司, 佐分利能生, 渋谷恒文, 鈴島仁, 塚田順一, 林真, 前田宏一, 松石英城, 松岡均, 牧野茂義, 田村和夫 . 造血器腫瘍治療時の感染症対策　九州血液疾患治療グループ(K-HOT)アンケート調査 . 臨床血液44 ( 7 ) 483 - 490 2003.7造血器腫瘍治療時の感染症対策　九州血液疾患治療グループ(K-HOT)アンケート調査

Publisher：(一社)日本血液学会-東京事務局

九州の22施設の血液内科で構成された九州血液疾患治療グループ(K-HOT)を対象に,造血器腫瘍治療時の感染症対策の現状把握を目的とした記名式アンケート調査を行った.一次調査は19施設より回答を得,その19施設を対象に二次調査を行った.その結果,病室の環境,医療従事者のガウン・マスクの使用,食事の管理は,原疾患や造血幹細胞移植(SCT)の方法によって異なった.感染症対策として,スルファトキサゾール・トリメトプリム(ST)合剤,ニューキノロン系薬剤,フルコナゾールの経口投与が多く使用されていたが,自家SCTでは簡素化されていた.成人T細胞白血病リンパ腫に対しては,予防投薬としてST合剤や結核既往患者に対する抗結核薬を使用する施設が多く,顆粒球コロニー刺激因子投与の開始時期も他の疾患より早かった

Ishitsuka K. . Infection control for the treatment of hematological malignancies: a survey of the Kyushu Hematology Organization for Treatment Study Group (K-HOT) . [Rinshō ketsueki] The Japanese journal of clinical hematology44 ( 7 ) 483 - 490 2003.7

Oketani M. . Inhibition by arsenic trioxide of human hepatoma cell growth . Cancer Letters183 ( 2 ) 147 - 153 2002.9

Ishitsuka K, Utsunomiya A, Aosaki S, Tashiro Y, Takeshita T . [Indolent primary gastric adult T-cell leukemia/lymphoma with recurrent lesions limited to the stomach and duodenum]. . [Rinsho ketsueki] The Japanese journal of clinical hematology43 ( 7 ) 554 - 9 2002.7[Indolent primary gastric adult T-cell leukemia/lymphoma with recurrent lesions limited to the stomach and duodenum].

石塚賢治, 宇都宮與, 青崎真一郎, 田代幸恵, 竹下武承 . 上部消化管に再発を繰り返し慢性に経過した胃原発成人T細胞白血病/リンパ腫 . 臨床血液43 ( 7 ) 554 - 559 2002.7上部消化管に再発を繰り返し慢性に経過した胃原発成人T細胞白血病/リンパ腫

Publisher：(一社)日本血液学会-東京事務局

75歳男.胸焼けを主訴とした.上部消化管内視鏡検査にて胃前庭部大弯に平盤状隆起性病変,前庭部から体部の広範囲にわたり潰瘍を伴う隆起性病変がみられ,生検にて悪性リンパ腫と診断され,免疫染色にて腫瘍細胞はCD4陽性であり,可溶性IL-2レセプターの軽度上昇,血清抗HTLV-I抗体陽性であったことから胃原発急性型成人T細胞白血病/リンパ腫(ATLL)と診断した.多剤併用化学療法を施行し完全寛解となった.胃体上部から穹窿部の後壁に再発がみられたが放射線療法施行にて病変は消失し,胃体部大彎と十二指腸下行脚に2回目の再発を来たしたものの自然消失した.その後,全身性に再発し,多剤併用化学療法を行ったが無効で,肺炎を併発し呼吸不全にて死亡した.以上より,本症例は胃に初発後2年6ヵ月間病変が消化管に限局し緩慢な経過をとった点で極めて稀な症例であると考えられた

Ishitsuka K. . Indolent primary gastric adult T-cell leukemia/lymphoma with recurrent lesions limited to the stomach and duodenum . [Rinshō ketsueki] The Japanese journal of clinical hematology43 ( 7 ) 554 - 559 2002.7

Ikeda R. . Molecular basis for the inhibition of hypoxia-induced apoptosis by 2-deoxy-D-ribose . Biochemical and Biophysical Research Communications291 ( 4 ) 806 - 812 2002.3

Ishitsuka K. . Arsenic trioxide induces apoptosis in HTLV-I infected T-cell lines and fresh adult T-cell leukemia cells through CD95 or tumor necrosis factor α receptor independent caspase activation . Leukemia and Lymphoma43 ( 5 ) 1107 - 1114 2002

ISHITSUKA Kenji, UTSUNOMIYA Atae, AOSAKI Shin-ichiro, TASHIRO Yukie, TAKESHITA Taketsugu . Indolent primary gastric adult T-cell leukemia/lymphoma with recurrent lesions limited to the stomach and duodenum . Rinsho Ketsueki43 ( 7 ) 554 - 559 2002

Publisher：The Japanese Society of Hematology

A 75-year-old man visited our hospital complaining of heartburn in November 1997. Gastroscopical examination revealed ulcerous protruding extended from the gastric antrum to body and a flat, elevated lesion in the greater curvature of the stomach. Biopsy specimens revealed a CD4-positive malignant lymphoma. The serum anti-human T-lymphotrophic virus type I (HTLV-I) antibody test was positive. He was diagnosed as having primary gastric adult T-cell leukemia/lymphoma (ATLL; acute type). Complete remission was achieved with chemotherapy. In December 1998, the patient experienced a relapse. The lesions were limited to the region between the upper gastric body and the fornix and disappeared with radiation therapy. A second relapse was detected in the gastric greater curvature and descending portion of the duodenum in May 1999 but spontaneously disappeared in 5 months. The third relapse in May 2000 was systemic. Monoclonal integration of the HTLV-I provirus was observed in DNA extracted from ascitic lymphocytes. Chemotherapy was resumed, but the response was poor. The patient subsequently died of respiratory failure as a result of pneumonia. Although gastrointestinal involvement is frequent in ATLL, this appears to be a rare case of an idolent clinical course with lesions limited to the stomach and duodenum for 30 months.

DOI： 10.11406/rinketsu.43.554

Ishitsuka K, Hanada S, Suzuki S, Utsunomiya A, Chyuman Y, Takeuchi S, Takeshita T, Shimotakahara S, Uozumi K, Makino T, Arima T . Arsenic trioxide inhibits growth of human T-cell leukaemia virus type I infected T-cell lines more effectively than retinoic acids. . British Society of Haematology 103 ( 3 ) 721 - 728 2000.6Arsenic trioxide inhibits growth of human T-cell leukaemia virus type I infected T-cell lines more effectively than retinoic acids.Reviewed

Ishitsuka K. . Arsenic trioxide and the growth of human T-cell leukemia virus type I infected T-cell lines . Leukemia and Lymphoma37 ( 5-6 ) 649 - 655 2000

青崎真一郎, 濱田富志夫, 馬場泰忠, 古田敏久, 畠中真吾, 西俣寛人, 石塚賢治, 花田修一, 大石一郎, 美園俊明, 小倉芳人, 蓮井和久, 中村勇一, 尾辻真人, 南寛之, 島崎隆, 宇都宮與, 高崎能久 . 【AIDSとATLの消化管病変】ATLの消化管病変の臨床像 . 胃と腸34 ( 7 ) 857 - 872 1999.6【AIDSとATLの消化管病変】ATLの消化管病変の臨床像

Publisher：(株)医学書院

ATLの消化管浸潤は広範囲かつ高度で,多発性又はび漫性の浸潤病変が多い傾向にあった.画像所見の検討により浸潤・発育進展様式とその肉眼像を基本的に以下の3つに分類した. 1)腫瘍細胞が腫瘤をつくらず消化管壁を連続性にび漫性に浸潤するタイプで,肉眼像は粘膜面の凹凸が目立たない平坦病変を呈す-びまん浸潤型(表層型). 2)腫瘍細胞がリンパ装置に浸潤し腫瘤を形成するタイプで,肉眼像はMLP様の多発性の隆起性病変を呈す-多発結節型. 3)腫瘍細胞が多数のリンパ装置に浸潤し小さな腫瘤を形成するタイプで,肉眼像はたこいぼびらん様の小隆起がび漫性に多発した病変を呈す-多発びまん浸潤型

Kitazono M. . Prevention of hypoxia-induced apoptosis by the angiogenic factor thymidine phosphorylase . Biochemical and Biophysical Research Communications253 ( 3 ) 797 - 803 1998.12

Ishitsuka K. . Arsenic trioxide inhibits growth of human T-cell leukaemia virus type I infected T-cell lines more effectively than retinoic acids . British Journal of Haematology103 ( 3 ) 721 - 728 1998.12

松木田純香, 蓮井和久, 石塚賢治 . Hodgkin's病患者に出現した落屑を伴う皮膚硬化性病変 . 皮膚のリンフォーマXV 186 - 189 1996.8Hodgkin's病患者に出現した落屑を伴う皮膚硬化性病変

Publisher：皮膚リンフォーマ研究学会

34歳男.1990年,右頸部腫瘤が出現.生検され,Hodgkin's病結節硬化型と診断.1994年10月より腹部膨満出現,1994年12月,腹部CTで大動脈周囲に巨大な腫瘤を認め,肝,脾にも腫瘤を認めた.化学療法施行し,腹腔内腫瘤縮小傾向が認められたが,1995年4月頃より,全身性に落屑を伴う皮膚硬化性病変が出現.皮膚生検では,真皮上層から中層の血管周囲,表皮に小型〜中型の異型リンパ球の浸潤が認められた.免疫染色で,異型リンパ球は,主にCD4細胞で,CD8細胞を混じていた.TCRβ, TCRγ, Immunoglobulin heavy chain遺伝子の再構成の有無を,Hodgkin's病病変と,皮膚病変からのDNAで検討したが,再構成が認められなかった

OHNO Nobuhito, UOZUMI Kimiharu, ISHITSUKA Kenji, TAKATSUKA Yoshifusa, NAKANO Satoko, UTSUNOMIYA Atae, HANADA Shuichi, ARIMA Terukatsu, OSAME Hiromitu, KAI Motoaki, MIYAHARA Kenkichi, KUROIWA Yoshifumi . Adult T-cell Leukemia Complicated with Intestinal Tuberculosis . Journal of Atherosclerosis and Thrombosis37 ( 2 ) 139 - 144 1996.2

Publisher：Japan Atherosclerosis Society

We examined the serum lipids, apoproteins and lipoproteins, and several neutral sterols including cholestanol, desmosterol, lathosterol, campesterol and β-sitosterol in 45 male patients with coronary artery disease (CAD) and 40 normal control male subjects. The results were as follows: (1) Statistically significant differences between both groups were noted in triglycerides, high density lipoprotein cholesterol (HDL-Ch), low density lipoprotein cholesterol (LDL-Ch), β-lipoprotein (β-Lipo), apolipoprotein (Apo) A-I, Apo A-II, Apo B, β-Lipo/HDL-Ch, Apo B/Apo A-I, HDL-Ch/total cholesterol, and Atherogenic index, as reported previously. (2) Serum Lp (a) levels were significantly higher (p<0.001) in the CAD group (162.0±120.7mg/l) than in the control group (76.0±64.1mg/l). (3) No significant differences between both groups were noted in plant sterols (campesterol and β-sitosterol) and desmosterol. While, serum cholestanol, which was an intermediate metabolite in the cholesterol metabolic pathway, and lathosterol, which has been reported to be a good indicator of whole-body cholesterol synthesis, were significantly high in the CAD group. These results showed that patients with CAD had multiple risk factors in the metabolism of lipids, particularly of cholesterol, and lipoproteins.

SUEKAWA Kiyoyasu, MATSUMOTO Jun, OHNO Nobuhito, ISHIZUKA Kenji, ARIMA Terukatsu, MAEDA Masahiko, ISHIBE Ryohe, KUSANO Ken, SHIBUE Tadashi, TANAKA Sadao . A Case of Plasmacytoma of the Stomach . Gastroenterol Endosc38 ( 2 ) 325 - 330 1996.2

Ohno N. . Adult T-cell leukemia complicated with intestinal tuberculosis . [Rinshō ketsueki] The Japanese journal of clinical hematology37 ( 2 ) 139 - 144 1996.2

大納伸人, 魚住公治, 石塚賢治 . 経過中に腸結核を併発した成人T細胞白血病 . 臨床血液37 ( 2 ) 139 - 144 1996.2経過中に腸結核を併発した成人T細胞白血病

Publisher：(一社)日本血液学会-東京事務局

57歳男.発熱と呼吸困難を主訴に来院した.白血球数18,200/μl(異常リンパ球56%, CD4, CD25陽性,CD8陰性)抗HTLV-1抗体陽性より成人T細胞白血病(ATL)と診断し多剤併用化学療法を施行した.LDHは正常化し,表在リンパ節は縮小したが原因不明の発熱が続いた.化学療法続行中,回盲部の穿孔を起こし緊急手術を施行した.摘除標本には乾酪壊死と多数の結核菌を認め,腸結核と診断した

OHNO Nobuhito, UOZUMI Kimiharu, ISHITSUKA Kenji, TAKATSUKA Yoshifusa, NAKANO Satoko, UTSUNOMIYA Atae, HANADA Shuichi, ARIMA Terukatsu . Adult T-cell Leukemia Complicated with Intestinal Tuberculosis . Rinsho Ketsueki37 ( 2 ) 139 - 144 1996

Publisher：The Japanese Society of Hematology

We report a patient with adult T-cell leukemia (ATL) complicated with intestinal tuberculosis. A 57-year old man was admitted to our hospital because of fever and dyspnea. He was diagnosed as ATL by leukocytosis [leukocyte count 18,200/μl with 56% of abnormal lymphocytes which express CD4(+) and CD25(+)] and seropositive result of anti-HTLV-1 antibody. Combination chemotherapy for ATL improved his serum LDH level and peripheral lymph nodes, but fever was still persistent. He had an emergency operation because of perforation of the cecum during the chemotherapy. Histological examination of the resected cecum revealed caseous necrosis and numerous mycobacterium, which induced a diagnosis of intestinal tuberculosis. Although there have been several reports on pulmonary tuberculosis in patients with ATL, this is the first report of intestinal tuberculosis in ATL as far as we know. We conclude that if the patients with ATL have persistent fever of unknown origin, we should take account of intestinal tuberculosis as one of differential diagnosis.

DOI： 10.11406/rinketsu.37.139

SUEKAWA Kiyoyasu, TANANA Sadao, MATSUMOTO Jun, OHNO Nobuhito, ISHIZUKA Kenji, ARIMA Terukatsu, MAEDA Msashiko, ISHIBE Ryohei, KUSANO Ken, SHIBUE Tadashi . A CASE OF PLASMACYTOMA OF THE STOMACH . GASTROENTEROLOGICAL ENDOSCOPY38 ( 2 ) 325 - 330_1 1996

Publisher：Japan Gastroenterological Endoscopy Society

A65-year-old female was advised to undergo further examination at a mass examlna-tion of the stomach. Endoscopy at our department showed granular changes in the mucosa with redness and unclear margins at the gastric angulus. Macroscopic examination revealed morphological resemblance to a superficial type malignant lymphoma or reactive, lymphoreticukar hyperplasia of the stomach. Peripheral blood examination and myelo-grams showed no abnormality. A diagnosis of plasmacytoma was made by biopsy, and surgical operation was performed. The tumor was histopathologically gastric plas-macytoma and irnmunohistochemically the IgA/λtype. A part of the tumor extended to the submucosal layer, but no abnormality in the regional lymph nodes Was observed.

DOI： 10.11280/gee1973b.38.325

Otsuka M. . Expression of the intestinal T‐lymphocyte‐associated‐molecule recognized by the HML‐1 antibody on mononuclear cells from HTLV‐I‐infected subjects . American Journal of Hematology50 ( 1 ) 1 - 8 1995.9

MAKINO Torahiko, UTSUNOMIYA Atae, SUZUKI Shinsuke, ISHIZUKA Kenji, NAKAHARA Katsushi, TAKESHITA Taketsugu, DAINO Nobuhito, CHUMA Yoshiko, OTSUKA Maki, UOZUMI Kimiharu, HANADA Shuichi, ARIMA Terukatsu, TOKUNAGA Masayoshi . Double Cancer in Patients with Adult T cell Leukemia . Rinsho Ketsueki36 ( 8 ) 792 - 794 1995.8

Publisher：The Japanese Society of Hematology

We have studied the incidence and characteristics of associated neoplasms in 210 ATL patients. Twelve patients had other primary neoplasms and the incidence of double cancer was 5.7%. The additional malignancies in ATL patients consisted of 4 cases of stomach, 3 cases of colon and one of each lung, ovary, uterus, liver and bladder cancer. In metachronous double cancer patients, the neoplasm was found before the time of diagnosis of ATL in 5 out of 6 patients. Immunodeficiency due to HTLV-I infection as well as chemotherapy for the preceding neoplasm are suggested to be related to the leukemogenesis of ATL.

DOI： 10.11406/rinketsu.36.792

Uozumi K. . Combination chemotherapy (RCM protocol: Response-oriented cyclic multidrug protocol) for the acute or lymphoma type adult t-cell leukemia . Leukemia and Lymphoma18 ( 3-4 ) 317 - 323 1995

Uozumi K. . Significance of elevated levels of soluble factors in the cerebrospinal fluid in patients with, adult t-cell leukemia . Leukemia and Lymphoma19 ( 5-6 ) 437 - 445 1995

Utsunomiya A. . Oral administration of low-dow etoposide for maintenance chemotherapy in adult T cell leukemia patients . Japanese Journal of Cancer and Chemotherapy21 ( 6 ) 839 - 844 1994.6

Uozumi K. . Elevated soluble CD4 levels in the cerebrospinal fluid in patients with adult T‐cell leukemia . American Journal of Hematology46 ( 2 ) 95 - 100 1994.6

Ishibashi K. . Tumor necrosis factor-β in the serum of adult T-cell leukemia with hypercalcemia . Blood77 ( 11 ) 2451 - 2455 1991

石橋和明, 石塚賢治, 上田博一郎 . ATL患者血清sIL-2R測定の有用性 . 医学と薬学24 ( 5 ) 1205 - 1210 1990.11ATL患者血清sIL-2R測定の有用性

Publisher：(株)自然科学社

成人T細胞白血病(ATL)およびヒトT細胞白血病ウイルス(HTLV-1)キャリアーの血清中可溶性インターロキキン-2受容体(sIL-2R)を測定し,ATLの病状との変化を検討した.HTLV-1キャリアーでは,すべてsIL-2Rはカットオフ値以下であり,ATL発症例では1例を除きsIL-2Rは高値を示した.臨床経過を掌握できたATL患者の血清sIL-2Rは,病状に比例して推移していた.血清保存時の間接蛍光抗体法による末梢血リンパ球表面IL-2レセプター陽性細胞比率とsIL-2Rとの相関を回帰分析により検討すると,5%危険率で相関関係が確認された.血清LDH,血清Caとの相関を重回帰分析で検討し,sIL-2Rはいずれとも危険率1%で相関関係を認めた

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