Biphenyl-dihydrothiazole-cyclized peptide libraries for peptide ligand and drug discovery

Science China Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Language: Английский

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Diagnostic and Therapeutic Implications of the SUMOylation Pathway in Acute Myeloid Leukemia

Cancers, Journal Year: 2025, Volume and Issue: 17(4), P. 631 - 631

Published: Feb. 13, 2025

Epigenetics encompasses heritable and stable changes in gene expression caused by external chromosomal modifications, without altering the underlying DNA sequence. Epigenetic established during early development maintained through successive cell divisions, play a critical role regulating expression. Post-translational modifications (PTMs) are key aspect of epigenetics essential for modulating protein functionality, as well regulatory cellular processes, including proliferation, differentiation, metabolic pathways, tumorigenic events. Among these, small ubiquitin-related modifier (SUMOylation) system is reversible PTM mechanism that alters target interaction surfaces covalent binding to lysine residues, thereby influencing structure function. Acute myeloid leukemia (AML) highly aggressive malignancy characterized clonal expansion primitive hematopoietic stem cells lineage bone marrow. Despite recent advancements therapeutic strategies an improved understanding leukemogenic patient outcomes remain poor, particularly elderly populations. Consequently, efforts have focused on developing novel agents, co-targeting specific mutations or integrating targeted therapies into combinatorial chemotherapeutic regimens. Emerging evidence suggests SUMOylation plays significant AML pathogenesis treatment response, representing promising advanced disease cases. This review provides brief analysis functional highlights its potential target. We also discuss current knowledge gaps propose directions future research advance precision medicine approaches treatment.

Language: Английский

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Ultrasound-Driven Coassembly of Anticancer Drugs into Carrier-Free Particles

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

The evolution of drug resistance in tumor malignancies has necessitated advancements anticancer therapy. Drug combination therapy, which can burden cancer progression at multiple target sites, been used to address and includes the coencapsulation synergistic drugs within nanoparticle carriers. However, use organic inorganic carriers lead additional material-induced safety concerns, including inflammation antibody formation. Herein, we report an ultrasound-driven approach combine into carrier-free particles. Venetoclax (Vtx) (as a model drug) is combined with anthracycline drug, doxorubicin (Dox), or myeloid cell leukemia-1 inhibitor (S63845) form spherical, submicrometer-sized (∼200–1000 nm diameter) particles, consisting predominantly molecules stabilized by hydrophobic interactions. coassembled i.e., nanodrugs (NDs), display comparable 2-fold higher activity than free monocomponent NDs, respectively, Vtx-resistant SKOV-3 cells. NDs containing Vtx Dox increased survival xenograft-bearing mice least 6 days comparison 10 saline-treated mice. Microscopy analysis tissues confirmed greater tissue damage apoptosis induced those drugs. present findings highlight potential sono-driven assembled systems combining advantages high surface area slow-release particulate system action combat resistance.

Language: Английский

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The roles of phosphorylation of signaling proteins in the prognosis of acute myeloid leukemia

Pathology & Oncology Research, Journal Year: 2024, Volume and Issue: 30

Published: July 5, 2024

Signaling pathways of Retinoblastoma (Rb) protein, Akt-kinase, and Erk-kinase (extracellular signal-regulated kinase) have an important role in the pathogenesis acute myeloid leukemia. Constitutive activation these proteins by phosphorylation contributes to cell survival regulation cycle, proliferation proapoptotic signaling processes. According previous data phosphorylated forms represent a worse outcome for cancer patients. We investigated presence Rb (P-Rb), Akt (P-Akt) Erk (P-Erk) Western blot technique using phospho-specific antibodies bone marrow or peripheral blood samples 69 AML patients, 36 patients with myelodysplastic syndrome (MDS) 10 healthy volunteers. Expression level PTEN (Phosphatase tensin homolog) PHLPP (PH domain leucine-rich repeat Protein Phosphatase) phosphatases, negative regulators kinase pathway were also examined. tested effect on correlation known prognostic features AML. found 46.3% had detectable P-Rb, 34.7% P-Akt 28.9% P-Erk protein. 66.1% expressing PTEN, 38.9% PHLPP, 37.2% both 32.2% neither nor phosphatases. Compared nucleophosmin mutation (NPMc) was significantly less mutated P-Rb patients’ group more than 30 G/L leukocyte count diagnosis. present FAB type M5. The expression represented significant better overall (OS), while event-free (EFS) unfavorable cytogenetics phosphatases OS EFS, although differences not statistically significant. confirmed positive between PHLPP. Assessing Rb, may define subgroup who would benefit especially from new targeted treatment options complemented standard chemotherapy, it contribute monitoring remission, relapse progression

Language: Английский

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Introduction to Neoplasia

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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