Mitigation of Cisplatin-Induced Nephrotoxicity and Augmentation of Anticancer Potency via Tea Polyphenol Nanoparticles’ Codelivery of siRNA from CRISPR/Cas9 Screened Targets DOI

Lingjiao Li,

Chengyao Feng,

Wenchao Zhang

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(44), P. 59721 - 59737

Published: Oct. 26, 2024

Cisplatin, a frontline chemotherapeutic agent against cancer, faces challenges in clinical application due to significant toxicities and suboptimal efficacy. Renal toxicity, dose-limiting factor of cisplatin, results from multifactorial processes including cisplatin-induced cellular pyroptosis, oxidative damage, inflammatory responses. Our findings reveal that Tea Polyphenols Nanoparticles (TPNs) derived Epigallocatechin gallate (EGCG) effectively could address these diverse mechanisms, comprehensively alleviating nephrotoxicity. Leveraging TPNs as carriers, chemical conjugation enables the encapsulation tetravalent cisplatin prodrug, extending its systemic half-life, enhancing tumor tissue accumulation, while simultaneously mitigating renal toxicity. Concurrently, employing CRISPR/Cas9 kinase library, we identified CSNK2A1 target sensitizing cells enabling specific siRNA sequences augment susceptibility, thereby minimizing dosage requirement. Benefiting versatile carrier properties codeliver prodrug anti-CSNK2A1 siRNA, developed codelivery system, Pt-TPNs/siRNA. Pt-TPNs/siRNA not only enhances anticancer effects but also mitigates achieving efficacy reducing Mechanistic safety assessments nanoparticles were conducted at both animal levels, opening new avenues for improved utilization cisplatin.

Language: Английский

Deciphering the role of liquid-liquid phase separation in sarcoma: Implications for pathogenesis and treatment DOI

Zehao Cheng,

Hua Wang, Y M Zhang

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: 616, P. 217585 - 217585

Published: Feb. 23, 2025

Language: Английский

Citations

0
RFWD3 Reprograms Nucleotide Metabolism Through PHGDH to Induce Chemoresistance In Osteosarcoma DOI Creative Commons
Wenchao Zhang,

Chi Yin,

Lin Qi

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Abstract Chemoresistance represents a major challenge for osteosarcoma treatment. Despite the improved knowledge of cancer biology, core determinants cisplatin (DDP) resistance in remain unclear and deserve further exploration. Here, RFWD3 is identified as key regulator DDP sensitivity using genome‐wide CRISPR screen. It demonstrated that overexpressed post‐chemotherapy tissues compared to pre‐chemotherapy tissues. Knocking out increased cells Mechanistically, bound ubiquitinated PHGDH at Lys137 residue, promoting its degradation conserving cellular oxidized nicotinamide adenine dinucleotide (NAD + ). The resulting surplus NAD enhanced TCA cycle, leading production aspartic acid glutamic de novo nucleotide biosynthesis. In addition, virtual screening techniques are employed identify Lomitapide specific inhibitor RFWD3‐PHGDH interaction, capable disrupting binding between PHGDH. found exhibits significant synergistic anti‐osteosarcoma effect when combined with DDP. conclusion, role regulating metabolism revealed comprised targetable candidates overcoming chemoresistance osteosarcoma.

Language: Английский

Citations

0
Deep learning models in classifying primary bone tumors and bone infections based on radiographs DOI Creative Commons
Hua Wang, Yu He, Lu Wan

et al.

npj Precision Oncology, Journal Year: 2025, Volume and Issue: 9(1)

Published: March 13, 2025

Primary bone tumors (PBTs) present significant diagnostic challenges due to their heterogeneous nature and similarities with infections. This study aimed develop an ensemble deep learning framework that integrates multicenter radiographs extensive clinical features accurately differentiate between PBTs We compared the performance of model four imaging models based solely on utilizing EfficientNet B3, B4, Vision Transformer, Swin Transformers. The patients were split into external dataset (N = 423) internal [including training 1044), test 354), validation set 171)]. outperformed models, achieving areas under curve (AUCs) 0.948 0.963 sets, respectively, accuracies 0.881 0.895. Its surpassed junior mid-level radiologists was comparable senior (accuracy: 83.6%). These findings underscore potential in enhancing precision for infections (Research Registration Unique Identifying Number (UIN): researchregistry10483 details are available at https://www.researchregistry.com/register-now#home/registrationdetails/6693845995ba110026aeb754/ ).

Language: Английский

Citations

0
LINC00942 Accelerates Esophageal Cancer Progression by Raising PRKDC Through Interaction With PTBP1 DOI
Zhongqiu Wang, Shuo Li,

Xing Zhang

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(3)

Published: March 1, 2025

ABSTRACT Aberrantly expressed LINC00942 is participated in the progression of several cancers. However, function esophageal cancer (ESCA) unclear. The objective this study was to explore effect on ESCA and its possible molecular mechanisms. First, differentially lncRNAs were analyzed using GSE192662 microarray. catRAPID omics v2.1 applied predict proteins that might interact with LINC00942. SDS‐PAGE silver staining assay, RNA pull down, RIP assay utilized validate interacting Then, seq detect downstream targets PTBP1, KEGG enrichment analysis used analyze genes involved proliferation migration‐related signaling pathways. In addition, CCK‐8, EdU transwell impact cell function. Bioinformatics revealed significantly overexpressed ESCA. Patients low‐expression had an obviously better prognosis. After knockdown, migration TE‐1 OE19 dramatically reduced. Subsequently, PTBP1 found LINC00942, PRKDC a target PTBP1. Functional showed markedly elevated after overexpression, knockdown reversed effect. Mechanistically, promoted expression by summary, facilitated cells via binding promote expression.

Language: Английский

Citations

0
Transforming cancer treatment: integrating patient-derived organoids and CRISPR screening for precision medicine DOI Creative Commons

Ziyi Zhu,

John Paul Shen,

Paul Chi-Lui Ho

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 25, 2025

The persistently high mortality rates associated with cancer underscore the imperative need for innovative, efficacious, and safer therapeutic agents, as well a more nuanced understanding of tumor biology. Patient-derived organoids (PDOs) have emerged innovative preclinical models significant translational potential, capable accurately recapitulating structural, functional, heterogeneous characteristics primary tumors. When integrated cutting-edge genomic tools such CRISPR, PDOs provide powerful platform identifying driver genes novel targets. This comprehensive review delves into recent advancements in CRISPR-mediated functional screens leveraging across diverse types, highlighting their pivotal role high-throughput genomics microenvironment (TME) modeling. Furthermore, this highlights synergistic potential integrating CRISPR immunotherapy, focusing on uncovering immune evasion mechanisms improving efficacy immunotherapeutic approaches. Together, these technologies offer promise advancing precision oncology.

Language: Английский

Citations

0
Advancements in Osteosarcoma Therapy: Overcoming Chemotherapy Resistance and Exploring Novel Pharmacological Strategies DOI Creative Commons
Mahmoud Zhra, Shahid Akhtar Akhund,

Khalid S. Mohammad

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 520 - 520

Published: April 3, 2025

Osteosarcoma is recognized as the most prevalent primary bone malignancy, primarily affecting children and adolescents. It characterized by its aggressive behavior high metastatic potential, which often leads to poor patient outcomes. Despite advancements in surgical techniques chemotherapy regimens, prognosis for patients with osteosarcoma remains unsatisfactory, survival rates plateauing over past few decades. A significant barrier effective treatment development of resistance, complicates management disease contributes recurrence. This review article aims provide a comprehensive overview recent therapy, particularly overcoming resistance. We begin discussing current standard modalities, including resection conventional agents such methotrexate, doxorubicin, cisplatin. While these approaches have been foundational managing osteosarcoma, they are limited adverse effects variability efficacy among patients. To address challenges, we explore novel pharmacological strategies that aim enhance includes targeted therapies focusing on specific molecular alterations cells immunotherapeutic designed harness body’s immune system against tumors. Additionally, innovative drug delivery systems improve bioavailability existing treatments while minimizing toxicity. The also assesses mechanisms underlying efflux mechanisms, altered metabolism, enhanced DNA repair pathways. By synthesizing research findings, highlight potential new therapeutic resistance mechanisms. Ultimately, this seeks inform future directions clinical practices, underscoring need continued innovation treating outcomes rates.

Language: Английский

Citations

0
A novel perspective on bone tumors: advances in organoid research DOI Creative Commons
Zhengliang Ma, Yibing Liu, Rui Chen

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 8, 2025

Bone tumor organoids are three-dimensional cell culture models derived from patient tissues or cells, capable of highly replicating the growth patterns and interactions bone tumors in vitro . Current treatments for hindered by challenges such as drug resistance, recurrence, metastasis. Organoids enhance physiological relevance models, thereby improving treatment precision overcoming limitations current therapeutic approaches. Organoid technology has made preliminary applications research, including primary tumors, metastatic marrow-derived tumors. This review will explore establishment organoids, summarize their prospects various diseases, discuss integration with emerging technologies. Additionally, future directions organoid research be discussed. In future, expected to promote further development medicine.

Language: Английский

Citations

0
2β-methoxy-2-deethoxyphantomolin synergistically enhances epirubicin effect against triple-negative breast cancer via targeted inhibition of AKT and HR pathways DOI
Jianyi Gu,

Ronger You,

Na Zhao

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108453 - 108453

Published: April 1, 2025

Language: Английский

Citations

0
Mitigation of Cisplatin-Induced Nephrotoxicity and Augmentation of Anticancer Potency via Tea Polyphenol Nanoparticles’ Codelivery of siRNA from CRISPR/Cas9 Screened Targets DOI

Lingjiao Li,

Chengyao Feng,

Wenchao Zhang

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(44), P. 59721 - 59737

Published: Oct. 26, 2024

Cisplatin, a frontline chemotherapeutic agent against cancer, faces challenges in clinical application due to significant toxicities and suboptimal efficacy. Renal toxicity, dose-limiting factor of cisplatin, results from multifactorial processes including cisplatin-induced cellular pyroptosis, oxidative damage, inflammatory responses. Our findings reveal that Tea Polyphenols Nanoparticles (TPNs) derived Epigallocatechin gallate (EGCG) effectively could address these diverse mechanisms, comprehensively alleviating nephrotoxicity. Leveraging TPNs as carriers, chemical conjugation enables the encapsulation tetravalent cisplatin prodrug, extending its systemic half-life, enhancing tumor tissue accumulation, while simultaneously mitigating renal toxicity. Concurrently, employing CRISPR/Cas9 kinase library, we identified CSNK2A1 target sensitizing cells enabling specific siRNA sequences augment susceptibility, thereby minimizing dosage requirement. Benefiting versatile carrier properties codeliver prodrug anti-CSNK2A1 siRNA, developed codelivery system, Pt-TPNs/siRNA. Pt-TPNs/siRNA not only enhances anticancer effects but also mitigates achieving efficacy reducing Mechanistic safety assessments nanoparticles were conducted at both animal levels, opening new avenues for improved utilization cisplatin.

Language: Английский

Citations

1