A humanized trivalent Nectin-4-targeting nanobody drug conjugate displays potent antitumor activity in gastric cancer

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Май 16, 2024

Gastric cancer represents a highly lethal malignancy with an elevated mortality rate among patients, coupled suboptimal postoperative survival prognosis. Nectin-4, overexpressed oncological target for various cancers, has been exploited to create antibody-drug conjugates (ADCs) treat solid tumors. However, there is limited research on Nectin-4 ADCs specifically gastric cancer, and conventional immunoglobulin G (IgG)-based frequently encounter binding site barriers. Based the excellent tumor penetration capabilities inherent in nanobodies (Nbs), we developed Nectin-4-targeting Nb drug (NDCs) treatment of cancer.

Язык: Английский

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Different Drug Mobilities in Hydrophobic Cavities of Host–Guest Complexes between β-Cyclodextrin and 5-Fluorouracil at Different Stoichiometries: A Molecular Dynamics Study in Water

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 5888 - 5888

Опубликована: Май 28, 2024

Cyclodextrins (CDs) are cyclic oligosaccharides able to form noncovalent water-soluble complexes useful in many different applications for the solubilization, delivery, and greater bioavailability of hydrophobic drugs. The complexation 5-fluorouracil (5-FU) with natural or synthetic cyclodextrins permits solubilization this poorly soluble anticancer drug. In theoretical work, between β-CD 5-FU investigated using molecular mechanics (MM) dynamics (MD) simulations water. inclusion formed thanks favorable intermolecular interactions 5-FU. Both 1:1 1:2 β-CD/5-FU stoichiometries investigated, providing insight into their interaction geometries stability over time complexes, affect drug's mobility, suggesting a two-step release mechanism: fast more exposed hydrated drug molecule, freedom movement near rims, slow one less-hydrated well-encapsulated confined MD study drugs specific carriers at atomistic level, possible mechanism highlighting role impact concentration on kinetics process A comparison experimental data literature provides further insights.

Язык: Английский

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The function and mechanism of circRNAs in 5-fluorouracil resistance in tumors: biological mechanisms and future potential

Pathology - Research and Practice, Год журнала: 2024, Номер 260, С. 155457 - 155457

Опубликована: Июль 6, 2024

Язык: Английский

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Apigenin as an emerging hepatoprotective agent: current status and future perspectives

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Дек. 19, 2024

Apigenin (C

Язык: Английский

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PRMT1-Catalyzed NUSAP1 Methylation Enhances Notch2 Signaling and 5-FU Resistance in Gastric Cancer

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

5-Fluorouracil (5-FU) resistance remains a significant challenge in the treatment of gastric cancer, limiting its clinical efficacy. Our study identifies NUSAP1, nucleolar and spindle-associated protein, as key driver 5-FU cancer. Proteomic analyses 5-FU-resistant cancer cell lines revealed that NUSAP1 is significantly upregulated, functional studies demonstrated essential role promoting resistance, proliferation, migration, invasion, tumor growth. Mechanistic investigations undergoes asymmetric dimethylation (ADMA) at R418 R422, mediated by PRMT1, with R422 site being critical for function. interacts PEST domain Notch2 through site, inhibiting ubiquitination stabilizing expression, thereby activating signaling pathway. This pathway closely linked to progression chemoresistance. Inhibition PRMT1 or mutation abrogated NUSAP1’s ability stabilize regulate downstream signaling. These findings unveil novel mechanism which promotes highlight therapeutic potential targeting NUSAP1-Notch2 axis overcoming

Язык: Английский

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Targeted Modulation of Mitochondrial Oxidative Stress Ameliorates 5‐Fluorouracil‐Induced Renal Injury in BALB/c Mice

Oxidative Medicine and Cellular Longevity, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Background: The present study reports the protective effect conferred by scavenging mitochondrial oxidative stress (mtOS) in 5-fluorouracil (5-FU)-induced renal injury. Methods: 5-FU toxicity model was created administering (12 mg/kg b.w. intraperitoneally [i.p.], for 4 days) to male BALB/c mice. of mitochondria-targeted antioxidant (MTA), Mito-TEMPO coadministered at a dosage 0.1 i.p., established terms levels/expressions injury markers, histopathological alterations, DNA damage, proinflammatory mtOS, dysfunction, and modulation apoptotic proteins cell death. Results: A significant rise levels serum urea, uric acid, creatinine noted after administration animals. Immunohistochemical ELISA findings demonstrated decrease podocin conversely increase neutrophil gelatinase-associated lipocalin (NGAL) expression challenge. analysis further revealed Bowman's capsule dilation, glomerular condensation, vacuolar degeneration. treatment significantly lowered reversed expressions NGAL normal, restored normal histoarchitecture tissue. Mitochondrial reactive oxygen species (mtROS), mtLPO, activity enzyme complexes, defense status were improved protected group as compared group. Further, decreased 8-OHdG, reduction death, Bax, Bcl-2, caspase-3 group, indicating its against 5-FU-induced Conclusion: approach targeting mtOS using MTA, Mito-TEMPO, may prove safe adjuvant alleviating during chemotherapy.

Язык: Английский

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From Chemical Composition to Antiproliferative Effects Through In Vitro Studies: Honey, an Ancient and Modern Hot Topic Remedy

Nutrients, Год журнала: 2025, Номер 17(9), С. 1595 - 1595

Опубликована: Май 6, 2025

Honey is a natural product which has been used throughout time as food, spice, and medicine. Its therapeutic use its origins in direct empirical observations of various beneficial actions terms anti-infectious, anti-inflammatory, wound-healing effects, to an antiproliferative effect added. In the context malignant transformation, reductions chronic inflammation, antioxidant action, cell cycle arrest, apoptosis activation contribute this effect, achievements attributed mainly polyphenols composition. A multitude vitro studies performed on cultures try elucidate real mechanism(s) that can scientifically explain action. addition, adjuvant association with cytostatic therapy demonstrates promising enhancing cytotoxic but also reducing some adverse effects. Highlighting these allows for further perspectives be opened regarding honey prophylactic purposes, food supplement. Future will support identification effects patients tumors human body whole, moving from complex implications.

Язык: Английский

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PRMT1-catalyzed NUSAP1 methylation enhances Notch2 signaling and 5-FU resistance in gastric cancer

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Май 20, 2025

Язык: Английский

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Design, synthesis, and antitumor activity evaluation of BF3-o, m, p-phenylenediamine bridged with pyrimidine-indole BF3 adduction derivatives

Molecular Diversity, Год журнала: 2024, Номер 29(1), С. 425 - 437

Опубликована: Июль 19, 2024

Язык: Английский

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DNA binding studies and in-vitro anticancer studies of novel lanthanide complexes

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 279, С. 135048 - 135048

Опубликована: Авг. 30, 2024

Язык: Английский

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