Targeting PI3K/AKT/mTOR Signaling to Overcome Drug Resistance in Cancer

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 396, P. 111055 - 111055

Published: May 17, 2024

Language: Английский

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Biomimetic Nanoparticles: A Revolutionary Approach to Breast Cancer Therapy Using Cell Membrane Coatings

Journal of Drug Delivery Science and Technology, Journal Year: 2025, Volume and Issue: unknown, P. 106849 - 106849

Published: March 1, 2025

Language: Английский

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Gold Nanobiosensors: Pioneering Breakthroughs in Precision Breast Cancer Detection

European Journal of Medicinal Chemistry Reports, Journal Year: 2024, Volume and Issue: unknown, P. 100238 - 100238

Published: Oct. 1, 2024

Language: Английский

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Single-cell RNA sequencing reveals small extracellular vesicles derived from malignant cells that contribute to angiogenesis in human breast cancers

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 25, 2023

Breast cancer is the most common affecting women across world. Tumor endothelial cells (TECs) and malignant are major constituents of tumor microenvironment (TME), but their origin role in shaping disease initiation, progression, treatment responses remain unclear due to significant heterogeneity.Tissue samples were collected from eight patients presenting with breast cancer. Single-cell RNA sequencing (scRNA-seq) analysis was employed investigate presence distinct cell subsets microenvironment. InferCNV used identify cells. Pseudotime trajectory revealed dynamic process angiogenesis. We validated function small extracellular vesicles (sEVs)-derived protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B) vitro experiments.We performed single-cell transcriptomics factors associated angiogenesis identified twelve subclusters involved also TECs confirmed participation different stages angiogenesis, including communication other types via sEVs. Overall, research uncovered heterogeneity expression levels genes at angiogenesis.This study showed sEVs derived promote blood vessel formation by activating through transfer PPP1R1B. This provides a new direction for development anti-angiogenic therapies human

Language: Английский

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Microtubule‐associated proteins and enzymes modifying tubulin

Cytoskeleton, Journal Year: 2023, Volume and Issue: 80(3-4), P. 60 - 76

Published: Feb. 17, 2023

Microtubules (MTs) are essential for many cellular processes including establishment of cell shape and polarity, chromosome segregation, vesicle transport, nuclear positioning. Human cells express 22 tubulin isoforms that have both overlapping distinctive functions. Tubulins reversely polymerize to form cylindrical MTs, while MT-associated proteins (MAPs), posttranslational modifications (PTMs), mechanical forces regulate their To help researchers medicinal chemists, this review article lists 489 MAPs, 43 known enzymes mediate PTMs, 306 drugs influence the functions MTs MAPs discusses recent microtubule research. Readers able sort list based on name, size, functions, related human diseases, date discovery. The also contains links Uniprot Protein Atlas databases access further details such as protein structure, associated proteins, subcellular localization, expression levels in tissues, mutations, pathology. Because cytoskeleton is involved pathological tumorigenesis, invasion, developmental small molecules target MT hold potential treat these diseases listed.

Language: Английский

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A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS)

BMC Pharmacology and Toxicology, Journal Year: 2023, Volume and Issue: 24(1)

Published: Nov. 13, 2023

Abstract Background Pertuzumab is widely used for the treatment of HER2 + breast cancer. But its safety in real world should be continuously monitored. So, we evaluated pertuzumab by pharmacovigilance analyze based on related adverse events (AEs) from FDA Adverse Event Reporting System (FAERS) and find whether potential or uncertain were present. Methods In disproportionality analysis, four algorithms employed to detect signals FAERS between 2012 2022. addition, also MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2019 high-ROR (reporting odds ratio) pertuzumab. We collected onset times pertuzumab-associated AEs. Results From January December 2022, there are 39,190,598 AEs reported database, which 14,707 listed as ‘primary suspected (PS)’ drug. A total 115 (46 potential) significant preferred terms (PTs) conforming retained. Finally, detected that pertuzumab-induced occurred 12 organ systems. For pertuzumab, unexpected PTs found, including but not limited below PTs: haematotoxicity, cardiotoxicity, cardiomyopathy, mitral valve incompetence, tachycardia, intestinal perforation, hemorrhoids, erysipelas, dehydration, pneumonitis, skin toxicity, onychomadesis, cyanosis, circulatory collapse. found 9 strong (5 signals) 68 medium intensity (21 according IC 025 (information component). The (IC > 3.0) myelosuppression, cardiac dysfunction, ejection fraction decreased, interstitial lung disease, onychomadesis. Excluding unreported unreasonable time reports, a 2016 median was 117 days (4, 96), (Q1, Q3). Notably, most all ( n = 1133, 56%) cardiac-related 405, 53%) within one month after therapy. Conclusion Analysis data identified AEs, our findings supported continuous clinical monitoring, pharmacovigilance, further studies association some regarded with care. have pay attention first therapy prepare emergency measures, especially elderly patients cardiovascular diseases.

Language: Английский

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Efficacy and safety of sintilimab combined with trastuzumab and chemotherapy in HER2-positive advanced gastric or gastroesophageal junction cancer

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

Published: Feb. 14, 2025

Background To evaluate the efficacy and safety of sintilimab in combination with trastuzumab chemotherapy for HER2-positive advanced gastric/gastroesophageal junction cancer (GC/GEJC). Methods GC/GEJC patients admitted to our department between January 2018 October 2024 were included this study. Patients who received assigned cohort A, while alone B. The primary endpoints progression-free survival (PFS) overall (OS), secondary disease control rate (DCR), objective response (ORR), safety. Results A total 103 analyzed, 46 57 ORR was 65.2% compared 40.4% B, DCR 87.0% 70.2% median follow-up duration 14.0 months. Median PFS (mPFS) 9.4 months (95% CI: 5.6–13.2) 7.4 6.1–8.7) B (p = 0.089). OS (mOS) 16.4 11.5–21.3) versus 14.2 11.2–17.2) 0.069). Adverse events predominantly mild, no treatment-related deaths occurred. Conclusion Sintilimab combined showed promising acceptable GC/GEJC. However, statistically significant improvement outcomes observed alone.

Language: Английский

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RNF114 Interacts with EWSR1 to Regulate VEGFR2 in HER2-positive Breast Cancer

Journal of Cancer, Journal Year: 2025, Volume and Issue: 16(6), P. 1888 - 1904

Published: Feb. 28, 2025

RNF114, a member of the E3 ubiquitin ligase family, was first identified as zinc-binding protein that exhibits frequent genomic amplification across various cancers. Previous studies have shown inhibition RNF114 activity by Nimbolide treatment can result in trapping PARP1 and synthetic lethality BRCA-mutated cancers, suggesting its role tumor progress. However, it's important to reveal novel functions interacting molecules RNF114. Here, we described promotes proliferation autophagy with EWSR1 regulating VEGFR2 expression HER2-positive breast cancer (BC). Our results also showed is significantly overexpressed BC associated TNM stage poor prognosis patients. And knockdown suppresses proliferation, migration, invasion, cells. findings highlight transcriptional regulatory function BC, offering new insights into oncogenic contribution progression.

Language: Английский

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Multimodal diagnostic models and subtype analysis for neoadjuvant therapy in breast cancer

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

Published: March 18, 2025

Breast cancer, a heterogeneous malignancy, comprises multiple subtypes and poses substantial threat to women's health globally. Neoadjuvant therapy (NAT), administered prior surgery, is integral breast cancer treatment strategies. It aims downsize tumors, optimize surgical outcomes, evaluate tumor responsiveness treatment. However, accurately predicting NAT efficacy remains challenging due the disease's complexity diverse responses across different molecular subtypes. In this study, we harnessed multimodal data, including proteomic, genomic, MRI imaging, clinical information, sourced from cohorts such as I-SPY2, TCGA-BRCA, GSE161529, METABRIC. Post data preprocessing, Lasso regression was utilized for feature extraction selection. Five machine learning algorithms were employed construct diagnostic models, with pathological complete response (pCR) predictive endpoint. Our results revealed that multi-omics Ridge model achieved optimal performance in pCR, an AUC of 0.917. Through unsupervised clustering using R package MOVICS nine algorithms, identified four distinct associated NAT. These exhibited significant differences proteomic profiles, hallmark gene sets, pathway activities, immune microenvironments, transcription factor characteristics. For instance, CS1 subtype, predominantly ER-positive, had low pCR rate poor chemotherapy drugs, while CS4 characterized by high infiltration, showed better immunotherapy. At single-cell level, detected heterogeneity microenvironment among Malignant cells displayed copy number variations, differentiation levels, evolutionary trajectories. Cell-cell communication analysis further highlighted differential interaction patterns subtypes, implications progression response. subtype provide novel insights into cancer. findings hold promise guiding personalized Future research should focus on experimental validation, in-depth exploration underlying mechanisms, extension these methods other cancers modalities.

Language: Английский

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Optimization of Clinical Trial Strategies for Anti-HER2 Drugs Based on Bayesian Optimization and Deep Learning

Published: Jan. 10, 2025

Language: Английский

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