Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 박병배 | - |
dc.date.accessioned | 2017-12-12T06:50:08Z | - |
dc.date.available | 2017-12-12T06:50:08Z | - |
dc.date.issued | 2016-02 | - |
dc.identifier.citation | INVESTIGATIONAL NEW DRUGS, v. 34, NO 1, Page. 1-14 | en_US |
dc.identifier.issn | 0167-6997 | - |
dc.identifier.issn | 1573-0646 | - |
dc.identifier.uri | https://link.springer.com/article/10.1007%2Fs10637-015-0301-z | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11754/34093 | - |
dc.description.abstract | Arsenic compounds have been used in traditional medicine for several centuries. KML001 (sodium metaarsenite; NaAsO2) is an orally bio-available arsenic compound with potential anti-cancer activity. However, the effect of KML001 has not been studied in lymphoid neoplasms. The aim of this study is to evaluate the anti-proliferative effect of KML001 in non-Hodgkin's lymphoma and to compare its efficacy with As2O3. KML001 inhibited cellular proliferation in all tested lymphoma cell lines as well as JurkatR cells (adriamycin-resistant Jurkat cells) in a dose-dependent manner, while As2O3 was not effective. Cell cycle regulatory protein studies have suggested that KML001 induces G1 arrest via p27-induced inhibition of the kinase activities of CDK2, 4, and 6. Treatment of KML001 induced apoptosis in Jurkat and JurkatR cells. The apoptotic process was associated with down-regulation of Bcl-2 (antiapoptotic molecule), up-regulation of Bax (proapoptotic molecule), and inhibition of caspase-3, -8, and -9. In addition, cell signaling including the STAT, PI3K/Akt, MAPK, and NF-kappa B signal pathways were inhibited in KML001-treated Jurkat and JurkatR cells. Furthermore, targeting the telomere by KML001 was observed in the Jurkat and JurkatR cells. The In vivo anti-tumoral activity of KML001 was confirmed in a xenograft murine model. Interestingly, partial responses were seen in two lymphoma patients treated with 10 mg/day (follicular lymphoma for 16 weeks and mantle cell lymphoma for 24 weeks) without severe toxicities. These findings suggest that KML001 may be a candidate agent for the treatment of de novo, refractory, and relapsed non-Hodgkin's lymphoma patients. | en_US |
dc.description.sponsorship | The present study was conducted at Hanyang University Hospital Clinical Laboratory and Seoul National University College of Pharmacy, and this work was supported by Komipharm International Co., Ltd., Seoul, Korea. | en_US |
dc.language.iso | en | en_US |
dc.publisher | SPRINGER | en_US |
dc.subject | Non-Hodgkin's lymphoma | en_US |
dc.subject | Sodium meta-arsenite | en_US |
dc.subject | KML001 | en_US |
dc.subject | Cell signal | en_US |
dc.subject | Telomere | en_US |
dc.title | Anti-tumoral effect of arsenic compound, sodium metaarsenite (KML001), in non-Hodgkin's lymphoma: an in vitro and in vivo study | en_US |
dc.type | Article | en_US |
dc.relation.no | 1 | - |
dc.relation.volume | 34 | - |
dc.identifier.doi | 10.1007/s10637-015-0301-z | - |
dc.relation.page | 1-14 | - |
dc.relation.journal | INVESTIGATIONAL NEW DRUGS | - |
dc.contributor.googleauthor | Yoon, Jin Sun | - |
dc.contributor.googleauthor | Hwang, Deok Won | - |
dc.contributor.googleauthor | Kim, Eun Shil | - |
dc.contributor.googleauthor | Kim, Jung Soon | - |
dc.contributor.googleauthor | Kim, Sujong | - |
dc.contributor.googleauthor | Chung, Hwa Jin | - |
dc.contributor.googleauthor | Lee, Sang Kook | - |
dc.contributor.googleauthor | Yi, Jun Ho | - |
dc.contributor.googleauthor | Uhm, Jieun | - |
dc.contributor.googleauthor | Park, Byeong Bae | - |
dc.relation.code | 2016003149 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | bbpark | - |
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