scholarly journals The novel anticancer agent JNJ-26854165 is active in chronic myeloid leukemic cells with unmutated BCR/ABL and T315I mutant BCR/ABL through promoting proteosomal degradation of BCR/ABL proteins

Oncotarget ◽  
2016 ◽  
Vol 8 (5) ◽  
pp. 7777-7790 ◽  
Author(s):  
Liangshun You ◽  
Hui Liu ◽  
Jian Huang ◽  
Wanzhuo Xie ◽  
Jueying Wei ◽  
...  
Keyword(s):  
Anticancer Agent ◽  
Leukemic Cells ◽  
The Novel ◽  
Proteosomal Degradation

Inhibition by CTP and UTP analogues of uridine kinase from mouse leukemic cells

1982 ◽  
Vol 47 (12) ◽  
pp. 3464-3469 ◽  
Author(s):  
Jiří Veselý ◽  
Ivan Rosenberg ◽  
Antonín Holý
Keyword(s):  
Leukemic Cells ◽  
The Novel ◽  
Uridine Kinase ◽  
Phosphate Donor

The new phosphonate analogues of CTP and UTP (CTPc and UTPc) inhibit the phosphorylation of uridine catalysed by uridine kinase in the presence of ATP and Mg2+-ions. The inhibition is competitive with respect to phosphate donor, and non-competitive with respect to phosphate acceptor. With respect to uridine the Ki constants for CTPc and UTPc are 7.5 . 10-5 mol l-1 and 1.0 . 10-4 mol l-1, respectively. With respect to ATP the Ki value for CTPc (3.6 . 10-6 mol l-1) is 3x lower than that for CTP. The novel analogues could be useful for further study of uridine kinase.

An excretion balance and pharmacokinetic study of the novel anticancer agent E7070 in cancer patients

2002 ◽  
Vol 13 (8) ◽  
pp. 807-814 ◽  
Author(s):  
HJG Desirée van den Bongard ◽  
Dick Pluim ◽  
Hilde Rosing ◽  
Lianda Nan-Offeringa ◽  
Margaret Schot ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Pharmacokinetic Study ◽  
Anticancer Agent ◽  
The Novel ◽  
Excretion Balance

Development of an LC–MS/MS method for analysis of interconvertible Z/E isomers of the novel anticancer agent, Bp4eT

2010 ◽  
Vol 397 (1) ◽  
pp. 161-171 ◽  
Author(s):  
Ján Stariat ◽  
Petra Kovaříková ◽  
Jiří Klimeš ◽  
Danuta S. Kalinowski ◽  
Des R. Richardson
Keyword(s):  
Anticancer Agent ◽  
The Novel

TGF-β Receptor Kinase Inhibitor LY2109761 Reverses the Anti-Apoptotic Effects of TGF-β1 in Leukemic Cells Co-Cultured with Stromal Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2846-2846
Author(s):  
Yoko Tabe ◽  
Yuanyuan Xu ◽  
Teresa McQueen ◽  
Michael Andreeff ◽  
Marina Konopleva
Keyword(s):  
Cell Proliferation ◽  
Stromal Cells ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
U937 Cells ◽  
The Novel ◽  
Β Receptor ◽  
Tgf Β1 ◽  
Cells Cultured

Abstract Transforming growth factor β1 (TGF-β1) is an essential regulator of cell proliferation, survival, and apoptosis, depending on the cellular context. TGF-β1 is also known to affect cell-to-cell interactions between tumor and stromal cells through production of the extracellular matrix and stimulation of integrin receptors. We investigated the role of TGF-β1 in the survival of human leukemic cells growing in the context of bone marrow (BM) microenvironment, and the anti-leukemia effects of the novel TGF-β receptor inhibitor LY2109761. BM-derived mesenchymal stem cells (MSC) produced TGF-β in an autocrine fashion. Treatment with rhTGF-β1 (2ng/mL) inhibited the spontaneous and Ara-C-induced apoptosis in U937 cells (% AnnexinV(+), control 34.5±8.4; TGF-β1 18.4±4.5; Ara-C 88.6±3.0; Ara-C/TGF-β1 60.4±8.0, p=0.04). These effects were more prominent in U937 cells co-cultured with MSC (% AnnexinV(+), control 19.4±2.8; TGF-β1 3.5±1.0; Ara-C 69.0±3.6; Ara-C+TGF-β1 24.9±3.3; p=0.01). In U937 cells co-cultured with MSC, rhTGF-β1 conferred higher cell protective effects on leukemia cells attached to MSC than on floating cells. Conversely, the pro-survival effects of TGF-β1 were inhibited by 5mM LY2109761 (%AnnexinV(+); MSC(−), control 31.8±2.3, TGF-β1 19.5±3.0, LY 28.4±4.4, TGF-β1+LY 37.7±2.0; MSC(+), control 22.1±1.7, TGF-β1 7.8±0.9, LY16.1±2.6, TGF-β1+ LY 18.0±1.1, p<0.01). Similar results were obtained using TGF-β1 neutralizing antibody. TGF-β1 induced pro-survival phosphorylation of Akt in U937 cells cultured alone or co-cultured with MSC, which was abrogated by LY2109761. Further, rhTGF-β1 induced a moderate increase in C/EBPβ gene and LAP isoform (cell cycle arrest inducing) of C/EBPβ protein in U937 cells cultured without MSCs, while markedly upregulating C/EBPβ gene and protein, both LIP (cell proliferation inducing) and LAP isoforms, under MSCs co-culture condition, suggesting the novel role of C/EBPβ in TGF-β1-mediated U937 cell survival. In summary, these results indicate that TGF-β1-secreting BM stromal cells promote the survival of U937 leukemia cells via direct cell-to-cell interaction and promote chemoresistance of leukemia cells through the activation of Akt signaling and upregulation of C/EBPβ. The blockade of TGF-β signaling by LY2109761, which effectively inhibited the pro-survival signaling, may enhance the efficacy of chemotherapy against leukemia cells in the BM microenvironment.

scholarly journals A Precise Nanostructure of Folate-Overhung Mitoxantrone DNA Tetrahedron for Targeted Capture Leukemia

Nanomaterials ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 951
Author(s):  
Ying-Zi Bu ◽  
Jia-Rui Xu ◽  
Qian Luo ◽  
Ming Chen ◽  
Li-Min Mu ◽  
...  
Keyword(s):  
Anticancer Agent ◽  
Evaluation Studies ◽  
Drug Loading ◽  
K562 Cells ◽  
Leukemic Cells ◽  
Dna Nanostructure ◽  
Dna Tetrahedron ◽  
Targeted Capture ◽  
Dna Strand

Regular chemotherapy cannot eliminate leukemic cells, due to the sparse distribution of cancer cells in leukemia patients. Here, we report a precise nanostructure of folate-overhung mitoxantrone DNA tetrahedron that enables the treatment of leukemic cells by targeted action. Folate is used as a targeting molecule and synthesized with DNA strand in forming the folate-overhang DNA complement, and the complement is then separately base-paired onto six sides of the fabricated DNA tetrahedron. Mitoxantrone is used as an anticancer agent and intercalated into the double strands of the folate-overhung DNA tetrahedron for drug loading. The evaluation studies are performed on leukemia BALL-1 and K562 cells. The results demonstrate that the folate-overhung mitoxantrone DNA tetrahedra (approximately 25nm) are able to target leukemic cells, transport across the nuclei membrane, induce the apoptosis, and enhance the overall efficacy of treating leukemic cells in vitro and in leukemia-bearing mice. This study provides a potential drug-containing DNA nanostructure, to clean the sparsely distributed leukemic cells in patients.

scholarly journals New Chloramphenicol Derivatives from the Viewpoint of Anticancer and Antimicrobial Activity

Antibiotics ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 9
Author(s):  
Panagiota Giannopoulou ◽  
Dionissia Missiri ◽  
Georgia Kournoutou ◽  
Eleni Sazakli ◽  
Georgios Papadopoulos ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Adverse Effects ◽  
Anticancer Activity ◽  
Bacterial Growth ◽  
Anticancer Agent ◽  
The Novel ◽  
Anticancer Properties ◽  
Antibacterial And Anticancer Activity ◽  
Alkyl Length

Over the last years, we have been focused on chloramphenicol conjugates that combine in their structure chloramphenicol base with natural polyamines, spermine, spermidine and putrescine, and their modifications. Conjugate 3, with spermidine (SPD) as a natural polyamine linked to chloramphenicol base, showed the best antibacterial and anticancer properties. Using 3 as a prototype, we here explored the influence of the antibacterial and anticancer activity of additional benzyl groups on N1 amino moiety together with modifications of the alkyl length of the aminobutyl fragment of SPD. Our data demonstrate that the novel modifications did not further improve the antibacterial activity of the prototype. However, one of the novel conjugates (4) showed anticancer activity without affecting bacterial growth, thus emerging as a promising anticancer agent, with no adverse effects on bacterial microflora when taken orally.

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