Distinct mRNA expression profiles and miRNA regulators of the PI3K/AKT/mTOR pathway in breast cancer: insights into tumor progression and therapeutic targets

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 9, 2025

Breast cancer remains a leading cause of mortality among women, driven by the molecular complexity its various subtypes. This study aimed to investigate differential expression genes and miRNAs involved in PI3K/AKT/mTOR signaling pathway, critical regulator progression. We analyzed tumor tissues from five breast subtypes-luminal A, luminal B HER2-negative, HER2-positive, triple-negative (TNBC)-and compared them with non-cancerous tissues. Microarray qRT-PCR techniques were employed profile mRNAs miRNAs, while bioinformatic tools predicted miRNA-mRNA interactions. Statistical analysis was performed statistical significance threshold (p) < 0.05. identified several upregulated across all subtypes, TNBC HER2-positive cancers showing most significant changes. Key such as COL1A1, COL4A1, PIK3CA, PIK3R1, mTOR found be overexpressed, correlating increased aggressiveness. miRNA revealed that miR-190a-3p, miR-4729, miR-19a-3p potentially regulate these genes, influencing pathway. For instance, reduced miR-190a-3p may contribute overexpression PIK3CA other pathway components, enhancing metastatic potential. Our findings suggest regulators play crucial roles progression, particularly aggressive subtypes like TNBC. The hold potential biomarkers for diagnosis treatment, but further validation functional studies is required. provides foundation targeted therapies at modulating this improve outcomes.

Language: Английский

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Synthesis and Characterization of Folic Acid-Functionalized DPLA-co-PEG Nanomicelles for the Targeted Delivery of Letrozole

ACS Applied Bio Materials, Journal Year: 2023, Volume and Issue: 6(5), P. 1806 - 1815

Published: April 24, 2023

An effective treatment for hormone-dependent breast cancer is chemotherapy using cytotoxic agents such as letrozole (LTZ). However, most anticancer drugs, including LTZ, are classified class IV biopharmaceuticals, which associated with low water solubility, poor bioavailability, and significant toxicity. As a result, developing targeted delivery system LTZ critical overcoming these challenges limitations. Here, biodegradable LTZ-loaded nanocarriers were synthesized by solvent emulsification evaporation nanomicelles prepared dodecanol-polylactic acid-co-polyethylene glycol (DPLA-co-PEG). Furthermore, cell-targeting folic acid (FA) was conjugated into the to achieve more safer treatment. During our investigation, DPLA-co-PEG DPLA-co-PEG-FA displayed uniform spherical morphology. The average diameters of 86.5 241.3 nm, respectively. Our preliminary data suggest that both nanoformulations cytocompatible, ≥90% cell viability across all concentrations tested. In addition, amphiphilic nature led high drug loading dispersion in water, resulting extended release up 50 h. According Higuchi model, functionalized FA have greater potential controlled target cells. This model confirmed experimentally, LTZ-containing significantly specifically (up 90% death) toward MCF-7 cells, human line, when compared free DPLA-co-PEG. half-maximal inhibitory concentration (IC50) 87 ± 1 nM achieved cells exposed DPLA-co-PEG-FA, whereas higher doses 125 2 100 required DPLA-co-PEG, Collectively, represents promising nanosized controllably drugs chemotherapeutics.

Language: Английский

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Tumor Microenvironment Reprogramming Improves Nanomedicine-Based Chemo-Immunotherapy in Sarcomas

Molecular Cancer Therapeutics, Journal Year: 2024, Volume and Issue: 23(11), P. 1555 - 1567

Published: June 28, 2024

Sarcomas are a heterogeneous group of rare cancers that originate in soft tissues or bones. Their complexity and tendency for metastases make treatment challenging, highlighting the need new therapeutic approaches to improve patient survival. The difficulties treating these primarily stem from abnormalities within tumor microenvironment (TME), which leads reduced blood flow oxygen levels tumors. Consequently, this hampers effective delivery drugs tumors diminishes efficacy despite higher toxic doses chemotherapy. In study, we tested mechanotherapeutic ketotifen combined with either pegylated liposomal doxorubicin (PLD) coencapsulated alendronate-doxorubicin (PLAD) plus anti-programmed cell death protein 1 antibody mouse models fibrosarcoma osteosarcoma. We found successfully reprogrammed TME by reducing stiffness increasing perfusion, proven changes measured shear-wave elastography contrast-enhanced ultrasound, respectively, enhanced our nanomedicine-based chemo-immunotherapy protocols. Furthermore, observed trend toward improved antitumor responses when nano-chemotherapy is given alongside immunomodulator alendronate was present treatment. next investigated mechanisms action combination. Ketotifen increased T-cell infiltration, specifically cytotoxic CD8+ T cells CD4+ helper cells, decreased number regulatory cells. addition, combination also altered polarization tumor-associated macrophages, favoring M1 immune-supportive phenotype over M2 immunosuppressive phenotype. Collectively, findings provide evidence ketotifen-induced reprogramming can sarcomas.

Language: Английский

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A landscape of recent advances in lipid nanoparticles and their translational potential for the treatment of solid tumors

Bioengineering & Translational Medicine, Journal Year: 2023, Volume and Issue: 9(2)

Published: Nov. 9, 2023

Abstract Lipid nanoparticles (LNPs) are biocompatible drug delivery systems that have found numerous applications in medicine. Their versatile nature enables the encapsulation and targeting of various types medically relevant molecular cargo, including oligonucleotides, proteins, small molecules for treatment diseases, such as cancer. Cancers form solid tumors particularly LNP‐based therapeutics due to enhanced permeation retention effect allows accumulate within tumor tissue. Additionally, LNPs can be formulated both locoregional systemic depending on type stage. To date, been used extensively clinic reduce toxicity improve outcomes cancer patients by encapsulating chemotherapeutic drugs. Next‐generation lipid currently being developed expand their use gene therapy immunotherapy, well enable co‐encapsulation multiple drugs a single system. Other developments include design targeted specific cells tissues, triggerable release control cargo at site. This review paper highlights recent LNP formulations focuses tumors, while also discussing some current translational limitations potential opportunities field.

Language: Английский

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Heterogeneity of cGMP signalling in tumour cells and the tumour microenvironment: Challenges and chances for cancer pharmacology and therapeutics

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 242, P. 108337 - 108337

Published: Jan. 6, 2023

Language: Английский

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Boosting antitumor efficacy of nanoparticles by modulating tumor mechanical microenvironment

EBioMedicine, Journal Year: 2024, Volume and Issue: 105, P. 105200 - 105200

Published: June 13, 2024

Nanoparticles have shown great potential for tumor targeting delivery via enhanced permeability and retention effect. However, the mechanical microenvironment, characterized by dense extracellular matrix (ECM), high stiffness solid stress, leads to only 0.7% of administered dose accumulating in tumors even fewer (∼0.0014%) reaching cells, limiting therapeutic efficacy nanoparticles. Furthermore, microenvironment can regulate cell stemness, promote invasion, metastasis reduce treatment efficacy. In this review, methods detecting are introduced. Strategies modulating including elimination ECM physical, chemical biological methods, disruption formation, depletion or inhibition cancer-associated fibroblasts, then summarized. Finally, prospects challenges further clinical applications mechano-modulating strategies enhance nanomedicines discussed. This review may provide guidance rational design application nanoparticles settings.

Language: Английский

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The synergistic potential of mechanotherapy and sonopermeation to enhance cancer treatment effectiveness

npj Biological Physics and Mechanics., Journal Year: 2025, Volume and Issue: 2(1)

Published: May 5, 2025

Language: Английский

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In Vitro Drug Repurposing: Focus on Vasodilators

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 671 - 671

Published: Feb. 20, 2023

Drug repurposing aims to identify new therapeutic uses for drugs that have already been approved other conditions. This approach can save time and resources compared traditional drug development, as the safety efficacy of repurposed established. In context cancer, lead discovery treatments target specific cancer cell lines improve patient outcomes. Vasodilators are a class shown potential influence various types cancer. These medications work by relaxing smooth muscle blood vessels, increasing flow tumors, improving delivery chemotherapy drugs. Additionally, vasodilators found antiproliferative proapoptotic effects on cells, making them promising repurposing. Research treatment has results in preclinical clinical studies. However, additionally research is needed fully understand mechanisms action determine optimal dosing combination therapy patients. this review, we aim explore molecular current state their option. With goal minimizing effort required hope shed light viable strategy

Language: Английский

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Design, synthesis, in vitro and in silico evaluation of indole-based tetrazole derivatives as putative anti-breast cancer agents

RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 15(4), P. 1329 - 1347

Published: Jan. 1, 2024

Design, synthesis, and in vitro silico evaluation of indole-based tetrazole derivatives as putative anti-breast cancer agents.

Language: Английский

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Targets in the Tumour Matrisome to Promote Cancer Therapy Response

Cancers, Journal Year: 2024, Volume and Issue: 16(10), P. 1847 - 1847

Published: May 11, 2024

The extracellular matrix (ECM) is composed of complex fibrillar proteins, proteoglycans, and macromolecules, generated by stromal, immune, cancer cells. components organisation the evolves as tumours progress to invasive disease metastasis. In many solid tumours, dense fibrotic ECM has been hypothesised impede therapy response limiting drug immune cell access. Interventions target individual ECM, collectively termed matrisome, have, however, revealed tumour-suppressor, tumour-promoter, immune-modulatory functions, which have complicated clinical translation. degree distinct matrisome can dictate tumour phenotypes subject intense study. A primary aim identify therapeutic opportunities within might support a better existing therapies. Many signatures developed predict prognosis, content, immunotherapy responses. this review, we will examine key associated with advanced resistance. We primarily focussed here on targeting components, rather than specific types, although several examples are described where cells origin dramatically affect roles for components. As unravel biochemical, biophysical, intracellular transduction mechanisms numerous be identified modify progression response.

Language: Английский

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