Translational Oncology, Год журнала: 2024, Номер 51, С. 102208 - 102208
Опубликована: Ноя. 26, 2024
Язык: Английский
Cancer Letters, Год журнала: 2024, Номер 590, С. 216823 - 216823
Опубликована: Март 21, 2024
Язык: Английский
Процитировано
8
Cancer Letters, Год журнала: 2024, Номер 588, С. 216744 - 216744
Опубликована: Март 1, 2024
Hepatocellular carcinoma (HCC) stands as a formidable global health challenge due to its prevalence, marked by high mortality and morbidity rates. This cancer type exhibits multifaceted etiology, prominently linked viral infections, non-alcoholic fatty liver disease, genomic mutations. The inherent heterogeneity of HCC, coupled with proclivity for developing drug resistance, presents obstacles effective therapeutic interventions. Autophagy, fundamental catabolic process, plays pivotal role in maintaining cellular homeostasis, responding stressors such nutrient deprivation. In the context tumor cells exploit autophagy, either augmenting or impeding activity, thereby influencing tumorigenesis. comprehensive review underscores dualistic autophagy acting both pro-survival pro-death mechanism, impacting trajectory anti-carcinogenic potential is evident ability enhance apoptosis ferroptosis HCC cells. Pertinently, dysregulated fosters resistance carcinogenic context. Both epigenetic factors can regulate progression. Recognizing paramount importance progression, this introduces pharmacological compounds capable modulating autophagy—either inducing inhibiting it, promising avenues therapy.
Язык: Английский
Процитировано
5
International Journal of Biological Macromolecules, Год журнала: 2024, Номер 265, С. 130997 - 130997
Опубликована: Март 19, 2024
Язык: Английский
Процитировано
5
Cancer Gene Therapy, Год журнала: 2025, Номер unknown
Опубликована: Апрель 1, 2025
Abstract Pancreatic cancer is an aggressive disease with low survival and high recurrence rates. A major obstacle in treating pancreatic the frequent development of chemoresistance to standard therapeutic drug, gemcitabine. One mechanism by which develops through proliferation stem cells (CSC). However, mechanisms regulating stemness chemoresistant tumors remain unclear. Here, we found that expression transcription factor Forkhead Box P1 (FOXP1) was elevated crucial for establishing CSC characteristics. Silencing FOXP1 reduced expressions stemness-associated genes diminished formation both spheroids colonies, highlighting role tumor cells. Mechanistically, discovered regulates ATP-binding cassette superfamily G member 2 (ABCG2), induces efflux Knockdown ABCG2, resulting decreased increased sensitivity Moreover, inhibition orthotopic mouse models growth proliferation, enhanced Together, our data reveal as a potent oncogene promotes cancer.
Язык: Английский
Процитировано
0
Nanoscale, Год журнала: 2024, Номер 16(24), С. 11610 - 11622
Опубликована: Янв. 1, 2024
Nanomedicine aims to develop smart approaches for treating cancer and other diseases improve patient survival quality of life. Novel nanoparticles as nanodiamonds (NDs) represent promising candidates overcome current limitations. In this study, NDs were functionalized with a 200 kDa hyaluronic acid-phospholipid conjugate (HA/DMPE), enhancing the stability in water-based solutions selectivity cells overexpressing specific HA cluster determinant 44 (CD44) receptors. These characterized by diffuse reflectance Fourier-transform infrared spectroscopy, Raman photoluminescence confirming efficacy functionalization process. Scanning electron microscopy was employed evaluate size distribution dry particles, while dynamic light scattering zeta potential measurements utilized ND behavior medium. Furthermore, biocompatibility uptake mediated CD44 receptors three different models human adenocarcinoma assessed performing cytofluorimetric assay confocal microscopy. HA-functionalized demonstrated advantage active targeting presence expressing on surface, suggesting higher drug delivery tumors over non-tumor tissues. Even CD44-poorly cancers could be targeted NDs, thanks their good passive diffusion within cells.
Язык: Английский
Процитировано
3
Cancer Letters, Год журнала: 2024, Номер 602, С. 217197 - 217197
Опубликована: Авг. 30, 2024
Pancreatic ductal adenocarcinoma (PDAC) is highly malignant and has a poor prognosis, without effective therapeutic targets in common gene mutations. Gemcitabine, first-line chemotherapeutic for PDAC, confers <10 % 5-year survival rate because of drug resistance. Y-box binding protein 1 (YBX1), associated with multidrug-resistance activation, remains unelucidated PDAC gemcitabine In vivo vitro, we verified YBX1's promotional effects, especially resistance, pancreatic cancer cells. YBX1-induced LRP1 transcription by to the promoter region significantly altered concentration distribution β-catenin Through TCF3, bound RRM1, key that promotes RRM1 expression. Combination therapy YBX1 inhibitor SU056 effectively reduced resistance vitro experiments. High expression promoted pathogenesis through YBX1-LRP1-β-catenin-RRM1 axis. Combining inhibitors may provide new direction combination chemotherapy overcome which frequently occurs during cancer. • Knockdown decreases viability levels. Pro-resistance effects are classical Wnt pathway. via YBX1-LRP1-β-Catenin-RRM1 improves efficacy PDAC.
Язык: Английский
Процитировано
3
European Journal of Pharmacology, Год журнала: 2024, Номер 965, С. 176330 - 176330
Опубликована: Янв. 14, 2024
Язык: Английский
Процитировано
1
Cell Death and Disease, Год журнала: 2024, Номер 15(5)
Опубликована: Май 16, 2024
Pancreatic cancer (PC) is among the deadliest malignancies, with an extremely poor diagnosis and prognosis. Gemcitabine (GEM) remains first-line drug for treating PC; however, only a small percentage of patients benefit from current immunotherapies or targeted therapies. Resistance to GEM prevalent affects long-term survival. We found that ubiquitin-protein ligase E3 module N-recognition 5 (UBR5) therapeutic target against resistance. UBR5 was markedly upregulated in clinical GEM-resistant PC samples cells. knockdown increased sensitivity cell lines. UBR5-mediated resistance accompanied by activation epithelial-mesenchymal transition (EMT) could be mitigated inhibiting EMT. Further analysis revealed promoted cells enhancing O-GlcNAcylation-mediated In addition, resulted O-GlcNAase (OGA) levels, essential negatively regulated enzyme O-GlcNAcylation process. identified negative association between OGA which further supported hypothesis induced OGA-dependent Mechanistic studies acts as ubiquitin regulates binding modulating OGA, facilitating its degradation ubiquitination. Additionally, high-throughput compound library screening using three-dimensional protein structure Food Drug Administration drug, Y-39983 dihydrochloride, potent sensitiser inhibitor. The combination dihydrochloride attenuated tumour growth mouse xenograft model. Collectively, these data demonstrated plays pivotal role sensitisation provides potential strategy overcome
Язык: Английский
Процитировано
1
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Июнь 8, 2024
SUMMARY Pancreatic ductal adenocarcinoma (PDAC) is recognized as one of the most lethal types cancer. Tunneling nanotubes (TNTs) are thin membranous intercellular communications, which allow cells to exchange intracellular material and promote cell fitness. We show here that PDAC increase formation TNTs upon exposure gemcitabine these contain ribosomal components. In PANC-1 line in explants obtained from patient biopsies, we observe polyadenylated RNA assembled 80S ribosomes within TNTs, indicating possibility an transfer translationally active ribosomes. Using with labelled small subunits (40S), demonstrate transport subunit via recipient cells. Our results can components translational machinery, including mRNA, may contribute resistance therapy, highlighting potential targeting TNT dynamics a therapeutic approach for PDAC. Highlights derived tumor biopsy samples form tunneling 2D culture Formation stimulated by 5.8S transferred activated Polyadenylated present Ribosomal detected Ribosomes cells, incorporated into
Язык: Английский
Процитировано
1
Journal of Biological Chemistry, Год журнала: 2024, Номер 300(4), С. 107171 - 107171
Опубликована: Март 15, 2024
Gemcitabine-based chemotherapy is a cornerstone of standard care for gallbladder cancer (GBC) treatment. Still, drug resistance remains significant challenge, influenced by factors such as tumor-associated microbiota impacting concentrations within tumors. Enterococcus faecium, member microbiota, was notably enriched in the GBC patient cluster. In this study, we investigated biochemical characteristics, catalytic activity, and kinetics cytidine deaminase E. faecium (EfCDA). EfCDA showed ability to convert gemcitabine its metabolite 2',2'-difluorodeoxyuridine. Both can induce cells. Moreover, determined crystal structure EfCDA, apo form complex with 2', 2'-difluorodeoxyuridine at high resolution. Mutation key residues abolished activity reduced Our findings provide structural insights into molecular basis recognizing bacteria CDA protein may potential strategies combat improve efficacy gemcitabine-based
Язык: Английский
Процитировано
0