Potential prognostic and immunologic significances of ADAM8 in clear cell renal cell carcinoma

Medicine, Journal Year: 2025, Volume and Issue: 104(5), P. e41375 - e41375

Published: Jan. 31, 2025

A Disintegrin And Metalloproteinase 8 (ADAM8) has been implicated in the development and progression of several cancers. However, further studies are needed to determine value ADAM8 ccRCC. The research aimed investigate prognostic immunologic significance ccRCC from perspective bioinformatics. We analyzed expression prognosis using Cancer Genome Atlas validated it with Gene Expression Omnibus immunohistochemistry assay. Functional enrichment analysis was conducted signaling pathways. relationship between tumor microenvironment CIBERSORT algorithm. Furthermore, study explored response immunotherapy by Immunome database data. Potential drugs for treating were discovered Connectivity Map. significantly elevated tissues. CcRCC patients higher levels had poorer prognosis, shown be an independent predictive risk factor functional revealed relevant we found that correlates strongly extent immune cell infiltration immunotherapy. Finally, 4 groups potential treatment identified. Our could have a significant impact on development, progression, ccRCC, may promising immunotherapeutic target. provides new insights useful helping manage

Language: Английский

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Recent Advances and Challenges in the Treatment of Advanced Pancreatic Cancer: An Update on Completed and Ongoing Clinical Trials

Cancers, Journal Year: 2025, Volume and Issue: 17(8), P. 1319 - 1319

Published: April 14, 2025

Pancreatic cancer is a deadly disease with low survival rate, particularly in its advanced stages. Advanced pancreatic remains major clinical challenge due to limited treatment options. Surgical resection may not always be feasible, and traditional chemotherapy often shows restricted effectiveness. As result, researchers are exploring multifaceted therapeutic approach targeting the genetic molecular drivers of disease. A combination profiling targeted therapies being investigated improve outcomes address shortcomings treatments. The focus this review provide summary current completed trials for cancer. This includes adagrasib (a KRAS inhibitor), olaparib PARP inhibitor BRCA mutations), APG-1387 (an IAP antagonist), minnelide anti-stromal agent), arimastat MMP MK-0646 IGF1R sirolimus mTOR metabolic inhibitors. These agents evaluated both as standalone treatments standard therapy. Furthermore, we have summarized novel approaches such vaccines ablation techniques emerging strategies We also examined challenges treating factors contributing failure, which offer valuable insights developing more effective innovative drug designs.

Language: Английский

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Antitumor Effect of Albendazole on Cutaneous Squamous Cell Carcinoma (SCC) Cells

BioMed Research International, Journal Year: 2019, Volume and Issue: 2019, P. 1 - 9

Published: June 9, 2019

Drug repurposing and/or repositioning is an alternative method to develop new treatment for certain diseases. Albendazole was originally developed as anthelmintic medication, and it has been used treat a variety of parasitic infestations. In this study, we investigated the antitumor effect albendazole putative action mechanism. Results showed that dramatically decreased cell viability SCC lines (SCC12 SCC13 cells). increased apoptosis-related signals, including cleaved caspase-3 PARP-1 in dose-dependent fashion. The mechanistic study induced endoplasmic reticulum (ER) stress, evidenced by increase CHOP, ATF-4, caspase-4, caspase-12. Pretreatment with ER stress inhibitor 4-PBA attenuated albendazole-induced apoptosis cells. addition, colony-forming ability cells, together inhibition Wnt/β-catenin signaling. These results indicate shows via regulation cancer stemness, suggesting could be repositioned cutaneous treatment.

Language: Английский

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Exosomes as Pleiotropic Players in Pancreatic Cancer

Biomedicines, Journal Year: 2021, Volume and Issue: 9(3), P. 275 - 275

Published: March 9, 2021

Pancreatic cancer (PC) incidence is rising and due to late diagnosis, combined with unsatisfactory response current therapeutic approaches, this tumor has an extremely high mortality rate. A better understanding of the mechanisms underlying pancreatic carcinogenesis paramount importance for rational diagnostic approaches. Multiple lines evidence have showed that exosomes are actively involved in intercellular communication by transferring their cargos bioactive molecules recipient cells within microenvironment systemically. Intriguingly, may exert both protumor antitumor effects, supporting or hampering processes play a role pathogenesis progression PC, including shifts metabolism, proliferation, invasion, metastasis, chemoresistance. They also dual PC immunomodulation, exerting immunosuppressive immune enhancement effects through several mechanisms. PC-derived induce systemic metabolic alterations, leading onset diabetes weight loss. Moreover, been described as promising prognostic biomarkers PC. Their potential application therapy drug carriers targets under investigation. In review, we provide overview multiple roles played biology specific cargo biomolecules exploitation early diagnosis treatment

Language: Английский

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FAT10 promotes chemotherapeutic resistance in pancreatic cancer by inducing epithelial-mesenchymal transition via stabilization of FOXM1 expression

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(5)

Published: May 25, 2022

Pancreatic cancer (PC) is one of the deadliest malignant tumors, and its resistance to gemcitabine chemotherapy primary reason for poor prognosis in patients. Ubiquitin-like protein FAT10 has recently been reported promote tumor resistance. In this study, expression PC was significantly higher than that adjacent noncancerous tissues. Increased related a late TNM stage decreased overall survival. Functional experiments revealed downregulating inhibits proliferation epithelial-mesenchymal transition (EMT) cells, promotes apoptosis enhances sensitivity chemotherapy. addition, upregulation increased FOXM1 protein. The effect reversed by overexpression, knockdown inhibited EMT driven overexpression. Mechanistically, stabilized competing with ubiquitin bind inhibiting ubiquitination-mediated degradation FOXM1. conclusion, FAT10-FOXM1 axis pivotal driver resistance, results provide novel insights into PC.

Language: Английский

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Invasive Colon Cancer Cells Induce Transdifferentiation of Endothelium to Cancer-Associated Fibroblasts through Microtubules Enriched in Tubulin-β3

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 20(1), P. 53 - 53

Published: Dec. 23, 2018

Colon cancer, the second leading cause of cancer-related deaths in world, is usually diagnosed invasive stages. The interactions between cancer cells and located their niche remain crucial mechanism inducing tumor metastasis. most important among those are cancer-associated fibroblasts (CAFs), heterogeneous group myofibroblasts transdifferentiated from numerous different origin, including endothelium. endothelial-to-mesenchymal transition (EndMT) associated with modulation cellular morphology, polarization migration ability as a result microtubule cytoskeleton reorganization. Here we reveal, for first time, that colon regulate EndMT endothelium via tubulin-β3 upregulation its phosphorylation. Thus, concluded therapies based on inhibition expression or phosphorylation, blocking tubulin-β3’s recruitment to microtubules, together anti-inflammatory chemotherapeutics, promising means treat advanced stages cancer.

Language: Английский

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Necroptosis as a Novel Facet of Mitotic Catastrophe

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3733 - 3733

Published: March 29, 2022

Mitotic catastrophe is a defensive mechanism that promotes elimination of cells with aberrant mitosis by triggering the cell-death pathways and/or cellular senescence. Nowadays, it known apoptosis, autophagic cell death, and necrosis could be consequences mitotic catastrophe. Here, we demonstrate ability DNA-damaging agent, doxorubicin, at 600 nM concentration to stimulate We observe inhibition caspase activity leads accumulation hallmarks in which RIP1-dependent necroptotic death triggered. The suppression autophagy chemical inhibitor or ATG13 knockout upregulates RIP1 phosphorylation death. Thus, certain conditions catastrophe, addition apoptosis autophagy, can precede necroptosis.

Language: Английский

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Discovering the mechanism of action of drugs with a sparse explainable network

EBioMedicine, Journal Year: 2023, Volume and Issue: 95, P. 104767 - 104767

Published: Aug. 24, 2023

BackgroundAlthough Deep Neural Networks (DDNs) have been successful in predicting the efficacy of cancer drugs, lack explainability their decision-making process is a significant challenge. Previous research proposed mimicking Gene Ontology structure to allow for interpretation each neuron network. However, these previous approaches require huge amount GPU resources and hinder its extension genome-wide models.MethodsWe developed SparseGO, sparse interpretable neural network, drug response cell lines Mechanism Action (MoA). To ensure model generalization, we trained it on multiple datasets evaluated performance using three cross-validation schemes. Its efficiency allows be used with gene expression. In addition, SparseGO integrates an eXplainable Artificial Intelligence (XAI) technique, DeepLIFT, Support Vector Machines computationally discover MoA drugs.FindingsSparseGO's implementation significantly reduced memory usage training speed compared other methods, allowing expression instead mutations as input data. improved accuracy enabled use repositioning. Furthermore, prediction 265 drugs train it. It was validated understudied such parbendazole PD153035.InterpretationSparseGO effective XAI method predicting, but more importantly, understanding response.FundingThe Accelerator Award Programme funded by Cancer Research UK [C355/A26819], Fundación Científica de la AECC Fondazione AIRC, Project PIBA_2020_1_0055 Basque Government Synlethal (RETOS Investigacion, Spanish Government).

Language: Английский

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Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma

Pharmaceuticals, Journal Year: 2021, Volume and Issue: 14(3), P. 280 - 280

Published: March 20, 2021

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis often possible only in latter stages disease, with patients already presenting an advanced or metastatic tumor. It also cancers poorest prognosis, a five-year survival rate around 5%. Treatment PDAC still major challenge, cytotoxic chemotherapy remaining basis systemic therapy. However, no advances have been made recently, and therapeutic options are limited highly toxic. Thus, novel urgently needed. Drug repurposing strategy for development treatments using approved investigational drugs outside scope original clinical indication. Since repurposed completed several drug process, broad range data available. when compared de novo development, time-efficient, inexpensive has less risk failure future trials. Several candidates investigated past years treatment PDAC, as single agents combination conventional chemotherapy. This review gives overview main that candidates, potential preclinical studies

Language: Английский

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Lipid-like gemcitabine diester-loaded liposomes for improved chemotherapy of pancreatic cancer

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 365, P. 112 - 131

Published: Nov. 22, 2023

Language: Английский

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