Scientists demonstrated a unique role for liver in modulating the pathogenesis of leukemic disease and suggest that the hepatic microenvironment may protect leukemia cells from chemotherapeutic challenge.
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The hepatic microenvironment uniquely protects leukemia cells through induction of growth and survival pathways mediated by LIPG | Cancer Discovery. (n.d.). Retrieved October 13, 2020, from https://cancerdiscovery.aacrjournals.org/content/early/2020/10/07/2159-8290.CD-20-0318 Cite
Investigators assessed the cytotoxicity of Au/Pt/ZnO nanoparticles by means of MTT assay, and analyzed apoptosis as well as the influence of the cultivation time and concentration of Au/Pt/ZnO nanoparticles on the percentage of dead cells.
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Scientists identified a constitutive mechanism of resistance to PARP inhibitor (PARPi). They report that the bone marrow microenvironment facilitates DNA double-strand break repair activity in leukemia cells to protect them against PARPi-mediated synthetic lethality.
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Le, B. V., Podszywalow-Bartnicka, P., Maifrede, S., Sullivan-Reed, K., Nieborowska-Skorska, M., Golovine, K., Yao, J.-C., Nejati, R., Cai, K. Q., Caruso, L. B., Swatler, J., Dabrowski, M., Lian, Z., Valent, P., Paietta, E. M., Levine, R. L., Fernandez, H. F., Tallman, M. S., Litzow, M. R., … Skorski, T. (2020). TGFβR-SMAD3 Signaling Induces Resistance to PARP Inhibitors in the Bone Marrow Microenvironment. Cell Reports, 33(1). https://doi.org/10.1016/j.celrep.2020.108221 Cite
The authors describe the circuitry of a transactivation system responsible for oncogenic self-renewal. MLL recruited RNA polymerase II to unmethylated CpG-rich promoters by its CXXC domain and activated transcription by transcriptional regulators, including the AF4 family/ENL family/P-TEFb complex, DOT1L, and p300/CBP histone acetyl transferases.
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Scientists investigated the potential and mechanisms of anti-melanoma action of minocycline.
[International Journal of Molecular Sciences]
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HSD17B4 was highly expressed in the vast majority of human cancers, and its methylation was present only in breast cancers and one lymphoblastic leukemia cell line.
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Yamashita, S., Hattori, N., Fujii, S., Yamaguchi, T., Takahashi, M., Hozumi, Y., Kogawa, T., El-Omar, O., Liu, Y.-Y., Arai, N., Mori, A., Higashimoto, H., Ushijima, T., & Mukai, H. (2020). Multi-omics analyses identify HSD17B4 methylation-silencing as a predictive and response marker of HER2-positive breast cancer to HER2-directed therapy. Scientific Reports, 10(1), 15530. https://doi.org/10.1038/s41598-020-72661-9 Cite
Compound BT5 demonstrated on-target activity in NUP98-NSD1 leukemia cells, including inhibition of histone H3 lysine 36 dimethylation and downregulation of target genes, and impaired colony formation in an NUP98-NSD1 patient sample.
[Nature Chemical Biology]
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Huang, H., Howard, C. A., Zari, S., Cho, H. J., Shukla, S., Li, H., Ndoj, J., González-Alonso, P., Nikolaidis, C., Abbott, J., Rogawski, D. S., Potopnyk, M. A., Kempinska, K., Miao, H., Purohit, T., Henderson, A., Mapp, A., Sulis, M. L., Ferrando, A., … Cierpicki, T. (2020). Covalent inhibition of NSD1 histone methyltransferase. Nature Chemical Biology, 1–8. https://doi.org/10.1038/s41589-020-0626-6 Cite
Investigators showed that blocking dipeptidyl‐peptidases using Val‐boroPro triggers a lytic form of cell death in primary human CD4 and CD8 T cells, while other prototypical inflammasome stimuli were not active.
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Investigators report that graft-versus-leukemia failed due to insufficient H60 presentation and T cell exhaustion. Leukemia-derived H60 was inefficiently cross-presented whereas direct T cell recognition of leukemia cells intensifies exhaustion.
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Researchers showed that LW-213 dose-dependently inhibited human cutaneous T-cell lymphoma cell lines with IC50 values of around 10 μM, meanwhile it potently inhibited primary leukemia cells derived from peripheral blood of T-cell lymphoma patients.
[Acta Pharmacologica Sinica]
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Yu, X., Zhu, M., Wang, J., Li, H., Hu, P., Qing, Y., Wang, X., Wang, H., Wang, Z., Xu, J., Guo, Q., & Hui, H. (2020). LW-213 induces cell apoptosis in human cutaneous T-cell lymphomas by activating PERK–eIF2α–ATF4–CHOP axis. Acta Pharmacologica Sinica, 1–11. https://doi.org/10.1038/s41401-020-0466-7 Cite
Researchers investigated the uptake behavior of various polymethine dyes on leukemia cell lines and searched for carrier proteins that guide dye transport using RNA interference.
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