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Arsenic Disulfide Induced Apoptosis and Concurrently Promoted Erythroid Differentiation in Cytokine-Dependent Myelodysplastic Syndrome-progressed Leukemia Cell Line F-36p with Complex Karyotype Including Monosomy 7

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Chinese Journal of Integrative Medicine 2014年第5期20卷 387-393页

作者：胡晓梅 Sachiko Tanaka Kenji Onda 袁博 Hiroo Toyoda 麻柔刘峰 toshihiko hirano Department of Clinical Pharmacology School of PharmacyTokyo University of Pharmacy and Life Sciences National Therapeutic Center of Hematology of Traditional Chinese Medicine Xiyuan HospitalChina Academy of Chinese Medical Sciences

Objective： Acute myeloid leukemia progressed from myelodysplastic syndrome （MDS/AML） is generally incurable with poor prognosis for complex karyotype including monosomy 7 （-7）. Qinghuang Powder （青黄, QHP）, which includes Qing Dai （ Indigo naturalis） and Xiong Huang （realgar） in the formula, is effective in treating MDS or MDS/AML even with the unfavorable karyotype, and its therapeutic efficacy could be enhanced by increasing the Xiong huang content in the formula, while Xiong huang contains 〉 90% arsenic disulfide （As2S2）. F-36p cell line was established from a MDS/AML patient with complex karyotype including -7, and was in cytokine-dependent. The present study was to investigate the effects of As2S2 on F-36p cells. Methods： Cell proliferation was measured by an 3-（4,5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） assay. Cell apoptosis was identified by Annexin V-staining. Cell viability was determined by a propidium iodide （PI） exclusion. Erythroid differentiation was evaluated by the expression of cell surface antigen CD235a （GpA）. Results： After treatment with As2S2 at concentrations of 0.5 to 16 p. mol/L for 72 h, As2S2 inhibited the proliferation of F-36p cells. The 50% inhibitory concentrations （IC50） of As2S2 against the proliferation of F-36p cells was 6 I~ mol/L. The apoptotic cells significantly increased in a dose-dependent mannar （P〈0.05）. The cell viabilities were significantly inhibited by As2S2 dose-dependent in a dose-dependent manner （P〈0.05）. Significant increases of CD235a-positive cells were concurrently observed （P〈0.05） also in a dose- dependent manner. Conclusions： As2S2 could inhibit proliferation and viability, induce apoptosis, and concurrently promote erythroid differentiation dose-dependently in F-36p cells. As2S2 can inhibit proliferation and viability, induce apoptosis, and concurrently promote erythroid differentiation in cytokine-dependent MDS-progressed human leukemia cell line F-36p with complex karyotype including -7

关键词： leukemia myelodysplastic syndromes arsenic disulfide karyotype F-36p apoptosis erythroid diffeerentiation

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Arsenic trioxide induces apoptosis equally to T lymphoblastoid leukemia MOLT-4 cells and P-gp expressing daunorubicin-resistant MOLT-4 cells

Arsenic trioxide induces apoptosis equally to T lymphoblasto...

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第六届全国中西医结合血液病学术会议

作者： toshihiko hirano Kitaro Oka Department of Clinical Pharmacology School of Pharmacy Tokyo University of Pharmacy and Life Science

Purpose:To investigate the effects of arsenic trioxide(As2O3)on T lymphoblastoidleukemia MOLT-4 cells and P—gp expressing daunorubicin-resistant MOLT-4(MOLT-4/DNR)***:Cell growth was measured by a MTT *** viability w...

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Rapid and Simple Analysis of <i>N</i>-Aspartylchlor in E6 (Talaporfin) Using Fluorescence Microtiterplate and Its Application for Determination in Cells, Tissues and Blood

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Journal of Cancer Therapy 2012年第5期3卷 521-527页

作者： Hiroko Yokoyama Miyabi Ebara Fuyuki Nakamura Aina Nanasawa Sachiko Tanaka Kenji Onda Kentaro Sugiyama Kazuhiko Kasuya Gulimire Muhetaer Motohide Shimazu toshihiko hirano Department of 3rd Surgery Tokyo Medical University Shinjuku Tokyo Japan Department of 5th Surgery Hachioji Medical Center Tokyo Medical University Tokyo Japan. Department of Clinical Pharmacology Tokyo University of Pharmacy and Life Sciences Tokyo Japan

N-aspartylchlorin e6 (talaporfin) concentrations in cancer cells, mouse liver tissues, and human plasma specimens were determined with fluorescence microtiter plate analysis. Talaporfin standard curves were obtained in each of the sample specimens of cells, mouse tissues, or human plasma including serial concentration of talaporfin. The correlation co-efficiencies (r2) of talaporfin standard curves were 0.99-1.00, and the CV less than 5%. Talaporfin incorporation into cells of human breast cancer cell line MCF-7 after incubating with 25 μg/mL talaporfin for up to 24 h revealed that the t-max of the drug incorporation was approximately 5 h, and the maximum drug concentration incorporated was 25 μg/107 cells. Talaporfin incorporation into MCF-7 cells was significantly decreased in the presence of 3 μg/mL cyc-losporine (p < 0.05). Balb/c nu/nu mice implanted human cholangiocarcinoma NOZ cells in liver were administered intravenously 5mg/mouse of talaporfin, and the tissues of normal liver and tumor, as well as plasma specimens, were analyzed for talaporfin concentrations. The mean (SD) of talaporfin concentration in plasma after 30 min of administration was 41.6 (2.3) μg/mL, while the level decreased to undetectable concentrations 2 h after administration. In contrast, the talaporfin concentrations in normal and tumor tissues after 30 min of administration were 1.1-7.8 μg/g tissue, and the level slightly increased or was almost maintained for up to 2-4 h after administration. The heparinized blood of the healthy subjects was incubated with 25 μg/mL talaporfin for up to 24 h. The plasma talaporfin concentration did not significantly change during the incubation, and thus talaporfin appears not to be incorporated into the blood cells. We established rapid and simple analysis procedures of talaporfin in biological specimens using a fluorescence microtiter plate assay. Using this assay procedure, the unique pattern of talaporfin disposition and pharmacokinetics were reveal

关键词： N-Aspartylchlorin E6 (Talaporfin) Fluorescence Microtiterplate Analysis Breast Tumor Cells Tumor-Bearing Mouse Human Plasma

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Arsenic trioxide induces apoptosis in MOLT-4 and its daunorubicin-resistant cell line via depletion of intracellular glutathione,disruption of mitochondrial membrane potential and activation of caspase-3

Arsenic trioxide induces apoptosis in MOLT-4 and its daunoru...

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第六届全国中西医结合血液病学术会议

作者： Xiao-Mei Hu toshihiko hirano Kitaro Oka 1 National Therapeutic Center of Hematology of Traditional Chinese Medicine, XiYuan Hospital, China Academy of Traditional Chinese Medicine, Beijing, P. R. China, 100091 2 Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

Purpose:To demonstrate that arsenic trioxide(AS2O3)induces apoptosis via mitochondri-al pathway in both parent T Iynlphoblastoid leukemia MOLT-4 cells and its daunorubicin(DNR)-resistant subline MOLT-4/DNR cells expre...

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Usefulness of urinary trypsinogen-2 and trypsinogen activation peptide in acute pancreatitis:A multicenter study in Japan

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World Journal of Gastroenterology 2019年第1期25卷 107-117页

作者： Hiroaki Yasuda Keisho Kataoka Yoshifumi Takeyama Kazunori Takeda Tetsuhide Ito toshihiko Mayumi Shuji Isaji Tetsuya Mine Motoji Kitagawa Seiki Kiriyama Junichi Sakagami Atsushi Masamune Kazuo Inui Kenji hirano Ryukichi Akashi Masamichi Yokoe Yoshio Sogame Kazuichi Okazaki Chie Morioka Yasuyuki Kihara Shigeyuki Kawa Masao Tanaka Akira Andoh Wataru Kimura Isao Nishimori Junji Furuse Isao Yokota Tooru Shimosegawa Department of Medicine Division of Gastroenterology and Hepatology Kyoto Prefectural University of Medicine Department of Surgery Kindai University Faculty of Medicine Department of Surgery National Hospital Organization Sendai Medical Center Department of Medicine and Bioregulatory Science Graduate School of Medical Sciences Kyushu University Department of Emergency Medicine University of Occupational and Environmental Health Department of Hepatobiliary-Pancreatic and Transplant Surgery Mie University School of Medicine Department of Gastroenterology Tokai University School of Medicine Department of Nutritional Sciences Nagoya University of Arts and Sciences Department of Gastroenterology Ogaki Municipal Hospital Division of Gastroenterology Tohoku University Graduate School of Medicine Department of Gastroenterology Fujita Health University Bantane Hospital Department of Gastroenterology Graduate School of Medicine University of Tokyo Department of Healthcare Center Kumamoto Regional Medical Center General Internal Medicine Japanese Red Cross Nagoya Daini Hospital The Third Department of Internal Medicine Division of Gastroenterology and Hepatology Kansai Medical University Third Department of Internal Medicine Nara Medical University Department of Gastroenterology Kitakyushu General Hospital Department of Internal Medicine Matsumoto Dental University Department of Surgery and Oncology Graduate School of Medical SciencesKyushu University Division of Gastroenterology Department of Internal Medicine Shiga University of Medical Science Department of Gastroenterological General Breast and Thyroid SurgeryYamagata University Faculty of Medicine Department of Gastroenterology and Hepatology Kochi Medical School Faculty of Medicine Department of Medical Oncology Kyorin University Department of Biostatistics Hokkaido University

BACKGROUND Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide(TAP) concentration have been reported as prognostic markers for the diagnosis of acute *** To reconfirm the validity of all these markers in the diagnosis of acute pancreatitis by undertaking a multi-center study in *** Patients with acute abdominal pain were recruited from 17 medical institutions in Japan from April 2009 to December 2012. Urinary and serum samples were collected twice, at enrollment and on the following day for measuring target markers. The diagnosis and severity assessment of acute pancreatitis were assessed based on prognostic factors and computed tomography(CT) Grade of the Japanese Ministry of Health, Labour, and Welfare *** A total of 94 patients were enrolled during the study period. The trypsinogen-2 dipstick test was positive in 57 of 78 patients with acute pancreatitis(sensitivity,73.1%) and in 6 of 16 patients with abdominal pain but without any evidence of acute pancreatitis(specificity, 62.5%). The area under the curve(AUC) score of urinary trypsinogen-2 according to prognostic factors was 0.704, which was highest in all parameter. The AUC scores of urinary trypsinogen-2 and TAP according to CT Grade were 0.701 and 0.692, respectively, which shows higher than other pancreatic enzymes. The levels of urinary trypsinogen-2 and TAP were significantly higher in patients with extended extra-pancreatic inflammation as evaluated by CT *** We reconfirmed urinary trypsinogen-2 dipstick test is useful as a marker for the diagnosis of acute pancreatitis. Urinary trypsinogen-2 and TAP may be considered as useful markers to determine extra-pancreatic inflammation in acute pancreatitis.

关键词： Acute pancreatitis Trypsinogen activation peptide Urinary trypsinogen-2 dipstick test

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