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Naha-shi, Japan

Nakama S.,University of Ryukyus | Nakama S.,Musashino Research Institute for Immunity | Ishikawa C.,University of Ryukyus | Ishikawa C.,Transdisciplinary Research Organization for Subtopics and Island Studies | And 3 more authors.
International Journal of Oncology | Year: 2011

We evaluated the effects of Bidens pilosa, a plant found in tropical and subtropical regions, and investigated the molecular pathways responsible for the anti-adult T-cell leukemia (ATL) effect. Water extracts of B. pilosa had growth suppressive effects on human T-cell leukemia virus type 1 (HTLV-1)-infected T-cell lines and ATL cells. B. pilosa extracts arrested cells in G 1 cell cycle and induced apoptosis of HTLV-1-infected T-cell lines. B. pilosa extracts inhibited also the phosphorylation of IκB kinase β and IκBα, and NF-κB-DNA binding, in conjunction with reduction of expression of proteins involved in G 1/S cell cycle transition and suppression of apoptosis. Reactive oxygen species played a role in B. pilosa-mediated suppression of NF-κB activity. B. pilosa extracts also inhibited the expression of JunB and JunD, resulting in suppression of AP-1-DNA binding. In animals harboring tumors of HTLV-1-infected T-cell origin, treatment with B. pilosa extracts suppressed tumor growth. Our results suggest that B. pilosa is a potentially useful medicinal plant for treatment of ATL. Source

Ishikawa C.,University of Ryukyus | Nakachi S.,University of Ryukyus | Senba M.,Nagasaki University | Sugai M.,Kyoto University | And 2 more authors.
Carcinogenesis | Year: 2011

Adult T-cell leukemia (ATL) is a T-cell malignancy associated with human T-cell leukemia virus type 1 (HTLV-1). Mutations of tumor suppressor genes have been described in ATL. Although Tax, a product of HTLV-1, is associated with cellular genetic aberrations, the mechanisms of such association are not fully clear. Activation-induced cytidine deaminase (AID) is involved in somatic DNA alterations of the immunoglobulin gene for amplification of immune diversity. However, inappropriate expression of AID acts as a genomic mutator that contributes to tumorigenesis. To gain insight into the molecular mechanism underlying the emergence of somatic mutations in various genes during leukemogenesis, we examined the expression of AID. HTLV-1-infected T-cell lines and ATL cells expressed high levels of AID compared with uninfected T-cell lines and normal peripheral blood mononuclear cells (PBMCs). Immunohistochemistry showed AID-positive ATL cells in lymph nodes and skin lesions. Infection of a human T-cell line and normal PBMCs with HTLV-1 induced AID expression. Tax transcriptionally activated AID gene through both the nuclear factor-kappaB subunit p50 and cyclic adenosine 3′,5′-monophosphate response element-binding protein signaling pathways. p50, which lacks a transactivation domain, interacted with the transcriptional coactivator Bcl-3 in HTLV-1-infected T cells. Thus, activation of p50/Bcl-3 complexes in T cells in response to Tax might explain the constitutive expression of AID in HTLV-1-infected T cells. The constitutive expression of AID in ATL cells can be speculated to result from mutations induced by the Tax-activated AID and/or other Tax-associated mutagenic mechanisms during the pre-leukemic stage, which cause functional modification within the AID promoter or in any of its cellular regulatory activator proteins. © The Author 2010. Published by Oxford University Press. All rights reserved. Source

Nakamura H.,University of Ryukyus | Tateyama M.,University of Ryukyus | Tasato D.,University of Ryukyus | Haranaga S.,University of Ryukyus | And 4 more authors.
Journal of Infection and Chemotherapy | Year: 2014

Background and objective: Previous studies have suggested that human immunodeficiency virus (HIV) infection and/or the airway colonization of Pneumocystis jirovecii (Pcj) impact on the progression of airway obstruction, such as chronic obstructive pulmonary disease (COPD). This study was aimed to evaluate the relationship between HIV infection, airway colonization of Pcj and airway obstruction in Japanese male patients. Methods: Case-control study of 49 HIV-positive and 257 HIV-negative men were enrolled in this study. Airway obstruction was determined by spirometry. Cigarette smoking was determined by a self report. Laboratory data were obtained from medical records. Among HIV positive patients, the airway colonization of Pcj was evaluated by induced sputum using the real time polymerase chain reaction method. Results: Forty-eight out of 49 (97.9%) HIV-positive patients received antiretroviral therapy, and their median CD4 cell counts were 491/μL (79-935). The prevalence of airway obstruction as determined by spirometry was 10.2% (5/49) in HIV-positive subjects and 2.4% (5/208) in HIV-negative subjects (p = 0.024). Compared with the control group, HIV-positive patients were significantly younger (median age 44 vs 40, p = 0.019). After adjusting for age, pack-years of smoking, HIV infectionwas an independent risk factor for airway obstruction (OR; 10.93, 95%CI 1.99-60.1, p = 0.006). None of patient was detected the airway colonization of Pcj. Conclusions: HIV infection was an independent risk factor for airway obstruction regardless of airway colonization of Pcj. Health-care providers should be aware of the increased likelihood of airway obstruction among HIV-positive patients. © 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. Source

Senba M.,Nagasaki University | Buziba N.,Moi University | Mori N.,Omoromachi Medical Center | Morimoto K.,Nagasaki University | Nakamura T.,Nagasaki University
Acta Virologica | Year: 2011

Kaposi's sarcoma (KS) had been endemic in Africa before the appearance of human immunodeficiency viruses (HIV) in 1985. Incidence of African KS has increased over the time and the risk of contracting KS become greater in HIV-positive as opposed to HIV-negative individuals. KS specimens were collected in 1981-2000 from 228 surgical cases originating from a KS-endemic area of Western Kenya and examined for Kaposi?s sarcoma-associated herpesvirus (KSHV) by an immunoperoxidase assay. The results showed that the specimens from 1981-1985 (before the HIV epidemic) were KSHV-positive in 10.3% in contrast to the KSHV positivity of 50.1-63.5% in 1986-2000. The linear increase of KSHV positivity in 1981-2000 was statistically significant. The most plausible explanation for the increased prevalence of KSHV in KS cases is that the endemic KS has changed to the epidemic one. Source

Mori N.,University of Ryukyus | Mori N.,Omoromachi Medical Center | Ishikawa C.,University of Ryukyus | Senba M.,Nagasaki University | And 2 more authors.
Biochemical Pharmacology | Year: 2011

We studied the effects of AZD1152, an Aurora B kinase inhibitor, on Burkitt's lymphoma (BL) and Hodgkin's lymphoma (HL) in human tissues and cell cultures and in a murine xenograft model of lymphoma. Aurora kinase A and B levels were assessed by RT-PCR and immunohistochemistry. They were aberrantly expressed in BL and HL cell lines, and in lymph nodes from patients with BL and HL. Next, activation of the Aurora B promoter was detected by reporter gene assays. The promoter activity of Aurora B kinase was high in BL cell lines and the Aurora B promoter contained a positive regulatory region between -74 and -104 from the transcription initiation site. AZD1152-hQPA had antiproliferative effects in the BL and HL cell lines studied; inhibited the phosphorylation of histone H3 and retinoblastoma proteins, and resulted in cells with >4 N DNA content. AZD1152-hQPA induced caspase-dependent apoptosis of some cell lines, demonstrated by loss of mitochondrial membrane potential, activation of caspase-9, followed by activation of caspase-3. This effect was accompanied by the inhibition of survivin expression. In vivo efficacy was determined in NOD/SCID/γcnull mice implanted with the Ramos human BL cell line. AZD1152 had anti-tumour effects in this murine xenograft model. There preclinical data suggest that the inhibition of Aurora B kinase is a potentially useful therapeutic strategy in BL and HL. © 2011 Elsevier Inc. All rights reserved. Source

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