Center for Chronic Viral Diseases

Kagoshima-shi, Japan

Center for Chronic Viral Diseases

Kagoshima-shi, Japan
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Katsuya H.,Fukuoka University | Katsuya H.,Kumamoto University | Shimokawa M.,Clinical Research Institute | Ishitsuka K.,Fukuoka University | And 18 more authors.
Blood | Year: 2017

Adult T-cell leukemia-lymphoma (ATL) has been divided into 4 clinical subtypes: acute, lymphoma, chronic, and smoldering. The aim of this study is to develop a novel prognostic index (PI) for chronic and smoldering ATL. We conducted a nationwide retrospective survey on ATL patients, and 248 fully eligible individuals were used in this analysis. In the univariate analysis, sex, performance status, log10(soluble interleukin-2 receptor [sIL-2R]), neutrophils count, and lymphadenopathy showed values of P < .05 in training samples. A multivariate analysis was performed on these factors, and only log10(sIL-2R) was identified as an independent prognostic factor in training samples. Using a regression coefficient of this variable, a prognostic model was formulated to identify different levels of risk: indolent ATL-PI (iATL-PI) 5 1.51 3 log10(sIL-2R [U/mL]). The values calculated by iATL-PI were divided into 3 groups using a quartile point. In the validation sample, median survival times (MSTs) were 1.6 years, 5.5 years, and not reached for patients in the high-, intermediate-, and low-risk groups, respectively (P < .0001). To make the scoring system clinically practicable, we simplified iATL-PI according to trichotomizing sIL-2R at 1000 and 6000 U/mL, using a quartile point. Patients with more than 6000 U/mL sIL-2R were categorized into the high-risk group, less than and equal to 1000 U/mL into the low-risk group, and the others into the intermediate-risk group, and MSTs were 1.6 years, not reached, and 5.5 years, respectively (P < .0001). iATL-PI has potential as a novel tool for a risk-adapted therapeutic approach. (Blood. 2017;130(1):39-47) © 2017 by The American Society of Hematology.

Nakamura M.,University of Tokyo | Aoyama A.,University of Tokyo | Salim M.T.A.,Center for Chronic Viral Diseases | Okamoto M.,Center for Chronic Viral Diseases | And 4 more authors.
Bioorganic and Medicinal Chemistry | Year: 2010

A phenanthridinone skeleton was derived from our previous researches on thalidomide and retinoids as a multi-template for generation of anti-viral lead compounds. Structural development studies focusing on anti-hepatitis C virus activity afforded 5-butyl-2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenanthridin-6(5H)-one (10) and 5-butylbenzo[b]phenanthridin-6(5H)-one (39), which showed EC50 values of approximately 3.7 and 3.2 μM, respectively. © 2010 Elsevier Ltd. All rights reserved.

Camargo M.C.,U.S. National Institutes of Health | Camargo M.C.,University of Illinois at Chicago | Murphy G.,U.S. National Institutes of Health | Koriyama C.,Kagoshima University | And 13 more authors.
British Journal of Cancer | Year: 2011

Background:Meta-analyses of the published literature indicate that about 9% of gastric cancers contain Epstein-Barr virus (EBV), with consistent and significant differences by sex and anatomic subsite. This study aimed to identify additional determinants of EBV positivity and their joint effects.Methods:From 15 international populations with consistent laboratory testing for EBV, we pooled individual-level data for 5081 gastric cancer cases including information on age, sex, subsite, histologic type, diagnostic stage, geographic region, and period of diagnosis. First, we combined population-specific EBV prevalence estimates using random effects meta-analysis. We then aggregated individual-level data to estimate odds ratios of EBV positivity in relation to all variables, accounting for within-population clustering.Results:In unadjusted analyses, EBV positivity was significantly higher in males, young subjects, non-antral subsites, diffuse-type histology, and in studies from the Americas. Multivariable analyses confirmed significant associations with histology and region. Sex interacted with age (P0.003) and subsite (P0.002) such that male predominance decreased with age for both subsites. The positivity of EBV was not significantly associated with either stage or time period.Conclusion:Aggregating individual-level data provides additional information over meta-analyses. Distinguishing histologic and geographic features as well as interactions among age, sex, and subsite further support classification of EBV-associated gastric cancer as a distinct aetiologic entity. © 2011 Cancer Research UK All rights reserved.

Yoshimitsu M.,Kagoshima University | White Y.,Center for Chronic Viral Diseases | Arima N.,Kagoshima University | Arima N.,Center for Chronic Viral Diseases
Recent Results in Cancer Research | Year: 2014

Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive peripheral T-cell malignancy that develops after long-term chronic infection with human T-cell lymphotropic virus type-1 (HTLV-1). Despite the recent advances in chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and supportive care, the prognosis for patients with ATL is one of the poorest among hematological malignancies; overall survival (OS) at 3 years is only 24 % in the more aggressive subtypes of ATLL. HTLV-1 is a human retrovirus infecting approximately 10-20 million people worldwide, particularly in southern and southeastern Japan, the Caribbean, highlands of South America, Melanesia, and Equatorial Africa. Despite this high frequency of human infection, only 2-5 % of HTLV-1-infected individuals develop ATLL. Three major routes of viral transmission have been established: (1) mother-to-child transmission through breast-feeding; (2) sexual transmission, predominantly from men to women; and (3) cellular blood components. Multiple factors (e.g., virus, host cell, and immune factors) have been implicated in the development of ATLL, although the underlying mechanisms of leukemogenesis have not been fully elucidated. No preventive vaccine against HTLV-1 is currently available, and interrupting the well-recognized primary modes of HTLV-1 transmission is the mainstay of ATLL prevention. Prevention of mother-to-child transmission through the replacement of breast-feeding has been shown to have the most significant impact on the incidence of HTLV-1 infection, and public health policies should consider the risk of malnutrition, especially in developing countries where malnutrition is the significant cause of infant mortality. © 2014 Springer-Verlag Berlin Heidelberg.

Hamada T.,Kagoshima University | White Y.,Center for Chronic Viral Diseases | Nakashima M.,Kagoshima University | Oiso Y.,Kagoshima University | And 4 more authors.
Molecules | Year: 2012

Through bioassay-guided isolation, five compounds with growth inhibitory activity on S1T, an adult T-cell leukemia (ATL) cell line, were isolated from the crude methanol extract of the aerial parts of Hyptis verticillata.

Kusano S.,Center for Chronic Viral Diseases | Eizuru Y.,Center for Chronic Viral Diseases
Biochemical and Biophysical Research Communications | Year: 2010

Kaposi's sarcoma-associated herpes virus (KSHV)-encoded latency-associated nuclear antigen (LANA) protein has been reported to interact with glycogen synthase kinase 3β (GSK-3β) and to negatively regulate its activity, leading to stimulation of GSK-3β-dependent β-catenin degradation. We show here that the I-mfa domain proteins, HIC (human I-mfa domain-containing protein) and I-mfa (inhibitor of MyoD family a), interacted in vivo with LANA through their C-terminal I-mfa domains. This interaction affected the intracellular localization of HIC, inhibited the LANA-dependent transactivation of a β-catenin-regulated reporter construct, and decreased the level of the LANA·GSK-3β complex. These data reveal for the first time that I-mfa domain proteins interact with LANA and negatively regulate LANA-mediated activation of Wnt signaling-dependent transcription by inhibiting the formation of the LANA·GSK-3β complex. © 2010 Elsevier Inc. All rights reserved.

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