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Rapamycin restores p14, p15 and p57 expression and inhibits the mTOR/p70S6K pathway in acute lymphoblastic leukemia cells.
Abstract The aim of the present study was to investigate the effects of rapamycin and its underlying mechanisms on acute lymphoblastic leukemia (ALL) cells. We found that the p14, p15, and p57 genes were not expressed in ALL cell lines (Molt-4 and Nalm-6) and adult ALL patients, whereas mTOR, 4E-BP1, and p70S6K were highly expressed. In Molt-4 and Nalm-6 cells exposed to rapamycin, cell viability decreased and the cell cycle was arrested at the G1/S phase. Rapamycin restored p14, p15, and p57 gene expression through demethylation of the promoters of these genes. As expected, rapamycin also increased p14 and p15 pr...
Source: International Journal of Hematology - September 11, 2015 Category: Hematology Authors: Li H, Kong X, Cui G, Ren C, Fan S, Sun L, Zhang Y, Cao R, Li Y, Zhou J Tags: Int J Hematol Source Type: research

Glucosylceramide synthase promotes Bcl-2 expression via the ERK signaling pathway in the K562/A02 leukemia drug-resistant cell line.
Abstract Multidrug resistance (MDR) to chemotherapeutic agents is a major obstacle to curative treatment of cancer. In various types of cancers, overexpression of glucosylceramide synthase (GCS) has been observed to be associated with MDR, thus making GCS a target for reversal of resistance. Our previous work demonstrated that GCS and Bcl-2 are co-overexpressed in the K562/A02 leukemia multidrug-resistant cell line compared with its sensitive counterpart, K562. In the present study, we investigated the effects of GCS on apoptosis in K562/A02 and the associated molecular mechanisms. Our results indicate that the in...
Source: International Journal of Hematology - October 4, 2014 Category: Hematology Authors: Wang Q, Zou J, Zhang X, Mu H, Yin Y, Xie P Tags: Int J Hematol Source Type: research

A role for activator of G-protein signaling 3 (AGS3) in multiple myeloma.
In this report, we delineate the anti-apoptotic role of AGS3 in multiple myeloma (MM). To do this, we developed a cell apoptotic model induced by doxorubicin in MM. Our data indicate that decreased expression of AGS3 is correlated with reduced levels of p-CREB in the apoptotic model. The negative role of AGS3 in cell apoptosis was further confirmed by knocking down AGS3. The microenvironment has been shown to influence tumor cell phenotype in response to chemotherapy. Since cell adhesion-mediated drug resistance remains a major obstacle for successful treatment of MM, we constructed a cell adhesion model in MM and detected...
Source: International Journal of Hematology - December 5, 2013 Category: Hematology Authors: Shao S, Huang X, Wang Y, He S, Xu X, Zhu X, Yang X, Ding Z, Yao L, Huang Y, Wang C Tags: Int J Hematol Source Type: research

Activating transcription factor 4, an ER stress mediator, is required for, but excessive ER stress suppresses osteoblastogenesis by bortezomib.
Abstract Endoplasmic reticulum (ER) stress is induced in matrix-producing osteoblasts and plays an essential role in osteoblastogenesis. Although the bone anabolic activity of proteasome inhibitors has been demonstrated, the roles of ER stress induced by proteasome inhibition in osteoblastogenesis remain largely unknown. Here we show that bortezomib translationally increases protein levels of activating transcription factor 4 (ATF4), a downstream mediator of ER stress, in bone marrow stromal cells and MC3T3-E1 preosteoblastic cells. The suppression of ATF4 expression by siRNA abrogated osteocalcin expression and m...
Source: International Journal of Hematology - May 25, 2013 Category: Hematology Authors: Nakamura S, Miki H, Kido S, Nakano A, Hiasa M, Oda A, Amou H, Watanabe K, Harada T, Fujii S, Takeuchi K, Kagawa K, Ozaki S, Matsumoto T, Abe M Tags: Int J Hematol Source Type: research