Metformin use and pancreatic ductal adenocarcinoma outcomes: a narrative review

ANZ Journal of Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Background Metformin is a diabetes medication with anti‐mitotic properties. A narrative review was performed to investigate people using metformin and the risk of developing pancreatic ductal adenocarcinoma (PDAC) as well survival outcomes in established PDAC. Methods Relevant studies on use PDAC were retrieved from PubMed including observational PDAC, randomized controlled trials treatment Results Of 367 searched, 26 fulfilled criteria for this review. not consistently associated reduced However, use, especially higher cumulative doses, some longer patients subgroup resectable more advanced (non‐resectable metastatic) Conclusion may be overall benefits but metastatic subgroup. The evidence date does support routine an adjuvant therapy

Language: Английский

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Drug Repurposing in Pancreatic Cancer: A Multi-Stakeholder Perspective to Improve Treatment Options for Pancreatic Cancer Patients

Cancer Management and Research, Journal Year: 2025, Volume and Issue: Volume 17, P. 429 - 440

Published: March 1, 2025

Pancreatic cancer (PC) remains one of the most challenging malignancies to treat. Current therapeutic options are unsatisfactory, and there is an urgent need for more effective less toxic drugs improve dismal prognosis PC. In recent years, drug repurposing (DR) has emerged as attractive strategy identify novel treatments PC by leveraging existing approved other indications. Through use electronic medical records, Artificial Intelligence, study metabolic pathways, signalling many approaches, it become much easier in years potential uses old drugs. Although policy, funding research attention this area steadily growing, major challenges efficient patient-centric DR be addressed. These include but not limited regulatory, financial barriers lack coordination collaboration among several sectors stakeholders. To explore opportunities associated with PC, a one-day multi-stakeholder meeting was held on 14th November 2024 Brussels, Belgium part REMEDi4ALL project. This provided platform researchers, clinicians, industry representatives, funders, regulatory experts, patient advocates discuss propose actions optimize accelerate Insights from support enhance treatment while highlighting importance systemic supportive changes policy landscapes, interdisciplinary collaboration, data sharing, involvement driving innovation. summary highlights key outcomes recommendations informing future efforts advance initiatives context

Language: Английский

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Diagnostic and prognostic roles of endothelial- and platelet-derived extracellular vesicles in cardiovascular diseases

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: May 16, 2025

Extracellular vesicles (EVs) are membrane-bound structures released by all cell types. They play a critical role in intercellular communication transferring their cargo, comprising proteins, lipids, metabolites, RNAs, miRNAs, and DNA fragments, to recipient cells. This transfer influences gene expression, signaling pathways, cellular behavior. Due ability alter the physiology of cells, EVs hold significant therapeutic potential. Additionally, implicated various physiological pathological processes, including immune regulation, cancer progression, cardiovascular diseases. have been detected many biological fluids, such as peripheral blood, saliva, urine, cerebrospinal fluid, breast milk. The cargo dynamically reflects state parent making them promising candidates for liquid biopsies clinical conditions. Specifically, different EV subtypes diseases studied, with both endothelial platelet-derived playing roles pathologies. review focuses on diagnostic prognostic potential diseases, highlighting subpopulations.

Language: Английский

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Transcriptomics, metabolomics, and in-silico drug predictions for liver damage in young and aged burn victims

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: June 2, 2023

Abstract Burn induces a systemic response affecting multiple organs, including the liver. Since liver plays critical role in metabolic, inflammatory, and immune events, patient with impaired often exhibits poor outcomes. The mortality rate after burns elderly population is higher than any other age group, studies show that of aged animals more susceptible to injury burns. Understanding aged-specific fundamental improving health care. Furthermore, no liver-specific therapy exists treat burn-induced damage highlighting gap burn therapeutics. In this study, we analyzed transcriptomics metabolomics data from young mice identify mechanistic pathways in-silico predict therapeutic targets prevent or reverse damage. Our study highlights pathway interactions master regulators underlie differential animals.

Language: Английский

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Drug Repurposing to Enhance Antitumor Response to PD-1/PD-L1 Immune Checkpoint Inhibitors

Cancers, Journal Year: 2022, Volume and Issue: 14(14), P. 3368 - 3368

Published: July 11, 2022

Monoclonal antibodies targeting the PD-1/PD-L1 immune checkpoint have considerably improved treatment of some cancers, but novel drugs, new combinations, and modalities are needed to reinvigorate immunosurveillance in immune-refractory tumors. An option elicit antitumor immunity against cancer consists using approved marketed drugs known for their capacity modulate expression functioning checkpoint. Here, we reviewed several types alter checkpoint, either directly via blockade PD-L1 or indirectly an action on upstream effectors (such as STAT3) suppress transcription induce its proteasomal degradation. Specifically, repositioning liothyronine, azelnidipine (and related dihydropyridine calcium channel blockers), niclosamide, albendazole/flubendazole, a few other modulators (repaglinide, pimozide, fenofibrate, lonazolac, propranolol) is presented. Their bind repress function offer perspectives combination with PD-1 targeted biotherapeutics. These affordable could be useful improve therapy cancer.

Language: Английский

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Unraveling new avenues in pancreatic cancer treatment: A comprehensive exploration of drug repurposing using transcriptomic data

Computers in Biology and Medicine, Journal Year: 2024, Volume and Issue: 185, P. 109481 - 109481

Published: Dec. 6, 2024

Language: Английский

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Pancreatic ductal adenocarcinoma: Emerging therapeutic strategies

Surgical Oncology, Journal Year: 2022, Volume and Issue: 43, P. 101803 - 101803

Published: July 7, 2022

Language: Английский

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Advancement and recent trends in seeking less toxic and more active anti-cancer drugs: Insights into thiourea based molecules

Main Group Chemistry, Journal Year: 2022, Volume and Issue: 21(3), P. 885 - 901

Published: Feb. 8, 2022

The finding of potent anticancer agents with low toxicity and high selectivity has remained valuable for human health. Thiourea derivatives are the most significant organic compounds integral typical characteristics numerous varieties natural products pharmaceutical agents. It exhibits various pharmacological properties, its analogues confer a great deal structural diversity that was proven to be advantageous in search novel therapeutic derivatives, which show beneficial antitumor activities, typically considered central core derivatives. They also have broad-ranging biological activities such as anti-inflammatory, antibacterial, antifungal, antitubercular, antihypertensive, antihistaminic, antiviral activities. Several FDA-approved drugs thiourea their market, currently progress through registration statuses or clinical stages, indicating promising drugs. current review is intended systematically provide comprehensive evidence recent developments treat types cancer. Furthermore, we hope this will helpful consideration seeking rational designs less toxic more active effective diagnostics

Language: Английский

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Effects of chloroquine and hydroxychloroquine on the sensitivity of pancreatic cancer cells to targeted therapies

Advances in Biological Regulation, Journal Year: 2022, Volume and Issue: 87, P. 100917 - 100917

Published: Sept. 29, 2022

Language: Английский

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Structural Dynamics-Driven Discovery of Anticancer and Antimetastatic Effects of Diltiazem and Glibenclamide Targeting Urokinase Receptor

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(8), P. 5415 - 5426

Published: Feb. 28, 2023

Diltiazem and glibenclamide are commonly used hypotensive antidiabetic drugs. This study reports the discovery of potential antitumor antimetastatic effects these two drugs using a structural dynamics-driven virtual screening targeting urokinase receptor (uPAR). Owing to uPAR's high flexibility, currently resolved crystal structures uPAR, all in ligand-bound states, provide limited representations its physiological conformation. To improve accuracy screening, we performed long-timescale molecular dynamics simulation obtained representative conformations apo-uPAR as targets for our screening. Experimentally, demonstrated that diltiazem bound uPAR with KD values micromolar range. In addition, both compounds effectively suppressed tumor growth metastasis uPAR-dependent manner vitro vivo. work not only provides potent inhibitors but also proof-of-concept on off-label uses glibenclamide.

Language: Английский

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