A versatile drug delivery system using streptavidin-tagged pegylated liposomes and biotinylated biomaterials
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Authors: Chen, Ming-Han; Soda, Yasushi; Izawa, Kiyoko; Kobayashi, Seiichiro; Tani, Kenzaburo; Maruyama, Kazuo; Tojo, Arinobu; Asano, Shigetaka
Abstract
Here we have developed a versatile liposome-mediated drug delivery system (DDS) allowing a strong bridge between the streptavidin-tagged liposome (SAL) and biotin (Bi)-tagged biomaterials which has strong affinity to surface proteins expressed in restricted cell lineages. This DDS was effective and specific for many leukemia cells in vitro and in vivo. When examining 6 human leukemia cell lines using calcein-encapsulated SALs in combination with Bi-granulocyte colony-stimulating factor (G-CSF), Bi-anti-CD33 monoclonal antibody (MAb) or Bi-anti-CD7 MAb, the fluorescent positive rate of each cell line was in almost proportion to degree of G-CSF receptor, CD33 or CD7 expression, respectively. More importantly, the binding ability was shown to be well maintained in a mouse xenograft model. Furthermore the cytosine arabinoside (AraC)-encapsulated SALs could kill the corresponding cells much more effectively in combination with Bi-biomaterials than free AraC, as expected. These findings strongly indicate that our SAL/Bi-biomaterial system could allow various types of medical agents to be delivered reliably and stably to the cells targeted. (C) 2013 Published by Elsevier B.V.
Normal karyotype acute myeloid leukemia with the CD7+CD15+CD34+HLA-DR + immunophenotype is a clinically distinct entity with a favorable outcome
ANNALS OF HEMATOLOGY
Authors: Iriyama, Noriyoshi; Asou, Norio; Miyazaki, Yasushi; Yamaguchi, Shunichiro; Sato, Shinya; Sakura, Toru; Maeda, Tomoya; Handa, Hiroshi; Takahashi, Masatomo; Ohtake, Shigeki; Hatta, Yoshihiro; Sakamaki, Hisashi; Honda, Sumihisa; Taki, Tomohiko; Taniwaki, Masafumi; Miyawaki, Shuichi; Ohnishi, Kazunori; Kobayashi, Yukio; Naoe, Tomoki
Abstract
Recently, the presence of CEBPA mutation was identified as an important prognostic factor for normal karyotype (NK) acute myeloid leukemia (AML). Because AML with CEBPA mutation is closely associated with CD7, CD15, CD34, and HLA-DR expression, we investigated the prognostic implications of CD7+ CD15+ CD34+ HLA-DR + immunophenotype in NK-AML. We analyzed the immunophenotype of 329 patients with NK-AML from the Japan Adult Leukemia Study Group (JALSG) AML97 population. NK-AML with the CD7+ CD15+ CD34+ HLA-DR + immunophenotype was classified as the CEBPA type, and NK-AML that did not meet this criterion was considered as the non-CEBPA type. The influence of the CEBPA status on event-free survival (EFS) and overall survival (OS) was assessed using log-rank test and a multivariate Cox proportional hazard regression model. Furthermore, the surface antigen expression profile in AML according to the CEBPA mutation status (monoallelic or biallelic) was also investigated. Of the 329 NK-AML patients that were studied, 39 and 243 were classified as having CEBPA and non-CEBPA type NK-AML, respectively. Patients with CEBPA type NK-AML had significantly better EFS and OS than those with non-CEBPA type NK-AML. Multivariate analysis showed that the CEBPA type and white blood cell (WBC) counts of > 20 x 10(9)/L were independent prognostic factors for EFS and OS. Moreover, NK-AML with the biallelic CEBPA mutation was more closely associated with CD34 positivity than that with the monoallelic CEBPA mutation. NK-AML with the CD7+ CD15+ CD34+ HLA-DR + immunophenotype is a clinically discrete entity, and this may have a possible role in risk stratification.