Pigment Epithelial-Derived Factor in Pancreatic and Liver Cancers—From Inflammation to Cancer

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2260 - 2260

Published: Oct. 4, 2024

Gastrointestinal (GI) cancers are among the leading causes of mortality worldwide. Despite emergence new possibilities that offer hope regarding successful treatment these cancers, they still represent a significant global health burden. These can arise from various cell types within gastrointestinal tract and may exhibit different characteristics, behaviors, approaches. Both prognosis outcomes GI remain problematic because tumors primarily diagnosed in advanced clinical stages. Current biomarkers limited sensitivity specificity. Therefore, when developing strategies for diagnosis it is fundamental importance to discover capable addressing challenges early-stage presence lymph node metastases. Pigment epithelial-derived factor (PEDF) has garnered interest due its inhibitory effects on migration proliferation cancer cells. This protein been suggested be involved inflammation-related diseases, including cancer, through mechanisms. It was also observed reducing level PEDF sufficient trigger an inflammatory response. suggests endogenous anti-inflammatory factor. Overall, versatile with diverse biological functions span across tissues organ systems. Its multifaceted activities make intriguing target therapeutic interventions neurodegeneration, metabolic disorders. review, first time, summarizes role pathogenesis selected potential utility early diagnosis, prognosis, this malignancy.

Language: Английский

---

Insights into genetic aberrations and signalling pathway interactions in chronic lymphocytic leukemia: from pathogenesis to treatment strategies

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Dec. 28, 2024

Abstract Chronic lymphocytic leukemia (CLL) is prevalent in adults and characterized by the accumulation of mature B cells blood, bone marrow, lymph nodes, spleens. Recent progress therapy introduction targeted treatments [inhibitors Bruton's tyrosine kinase (BTKi) or inhibitor anti-apoptotic B-cell lymphoma-2 (Bcl-2i) protein (venetoclax)] place chemoimmunotherapy have significantly improved outcomes patients with CLL. These advancements shifted importance traditional predictive markers, leading to a greater focus on resistance genes reducing significance mutations, such as TP53 del(17p). Despite significant CLL treatment, some still experience disease relapse. This due substantial heterogeneity well interconnected genetic mechanisms pathway adaptive therapies Although knowledge pathomechanism has expanded recent years, precise origins interplay between various factors remain incompletely understood, necessitating further research. review enhances molecular understanding describing how BCR signalling, NF-κB PI3K/AKT, ROR1 pathways sustain cell survival, proliferation, apoptosis. It also presents pathway-adaptive Identifying receptor (BCR) signalling pivotal driver progression, findings advocate personalized treatment strategies based profiling, emphasizing need for research unravel complex its associated improve patient outcomes.

Language: Английский

---

Anti-Inflammatory and Cancer-Preventive Potential of Chamomile (Matricaria chamomilla L.): A Comprehensive In Silico and In Vitro Study

Biomedicines, Journal Year: 2024, Volume and Issue: 12(7), P. 1484 - 1484

Published: July 5, 2024

Background and aim: Chamomile tea, renowned for its exquisite taste, has been appreciated centuries not only flavor but also myriad health benefits. In this study, we investigated the preventive potential of chamomile (Matricaria chamomilla L.) towards cancer by focusing on anti-inflammatory activity. Methods results: A virtual drug screening 212 phytochemicals from revealed β-amyrin, β-eudesmol, β-sitosterol, apigenin, daucosterol, myricetin as potent NF-κB inhibitors. The in silico results were verified through microscale thermophoresis, reporter cell line experiments, flow cytometric determination reactive oxygen species mitochondrial membrane potential. An oncobiogram generated comparison 91 anticancer agents with known modes action using NCI tumor panel significant relationships cytotoxic compounds, lupeol, quercetin to microtubule This hypothesis was confocal microscopy α-tubulin-GFP-transfected U2OS cells molecular docking lupeol tubulins. Both compounds induced G2/M cycle arrest necrosis rather than apoptosis. Interestingly, involved major mechanisms resistance established drugs (ABC transporters, TP53, or EGFR). Performing hierarchical cluster analyses proteomic expression data identified two sets 40 proteins determining sensitivity quercetin, further pointing multi-specific nature compounds. Furthermore, β-amyrin inhibited mRNA proinflammatory cytokines IL-1β IL6 (HEK-Blue Null1). Moreover, Kaplan–Meier-based survival target protein these performed mining TCGA-based KM-Plotter repository 7489 patients. Renal clear carcinomas (grade 3, low mutational rate, neoantigen load) significantly associated shorter patients, indicating that subgroups tumors might benefit inhibition Conclusion: study chamomile, positioning it a promising agent against inflammation cancer. Further research clinical studies are recommended.

Language: Английский

---

The Src family kinase inhibitor drug Dasatinib and glucocorticoids display synergistic activity against tongue squamous cell carcinoma and reduce MET kinase activity

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 18, 2024

Abstract Background Tongue squamous cell carcinoma (TSCC) is an aggressive cancer associated with a poor prognosis and limited treatment options, necessitating new drug targets to improve therapeutic outcomes. Our current work focuses on protein tyrosine kinases as well-known for successful therapies. Methods Western blot analysis of phosphorylation patterns in 34 TSCC lines identified Src family (SFKs) the main contributors. Inhibition SFKs PP2 Dasatinib led profound biological effects. A high-throughput screen 1600 FDA-approved drugs was performed three discover that act synergistically against viability. Glucocorticoids emerged potential candidates were further investigated 2D culture by 3D soft agar colony formation. Dexamethasone chosen major tool our analyses. Since glucocorticoids are known their pleiotropic actions cells, we analyzed effects cycle, senescence, autophagy signaling. Results panel showed surprisingly homogenous pTyr-protein pattern prominent 130 kDa pTyr-protein. SFK activity greatly reduced overall levels p130Cas phosphorylation. It also impaired viability combination promising synergistic activity. strong expression. suppressed MET kinase its key substrate Gab1. On cellular level, G1 cycle arrest, increased senescence enhanced autophagy. This reflected regulatory proteins, including CDKs cyclins. Conclusion first show clinically used solid tumors. Furthermore, effector Gab1 newly glucocorticoid targets. Given extensive research target various cancers, findings have advance future treatments.

Language: Английский

---

Diagnostics and Therapy for Malignant Tumors

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2659 - 2659

Published: Nov. 21, 2024

Malignant tumors remain one of the most significant global health challenges and contribute to high mortality rates across various cancer types. The complex nature these requires multifaceted diagnostic therapeutic approaches. This review explores current advancements in methods, including molecular imaging, biomarkers, liquid biopsies. It also delves into evolution strategies, surgery, chemotherapy, radiation therapy, novel targeted therapies such as immunotherapy gene therapy. Although progress has been made understanding biology, future oncology lies integration precision medicine, improved tools, personalized approaches that address tumor heterogeneity. aims provide a comprehensive overview state diagnostics treatments while highlighting emerging trends lie ahead.

Language: Английский

---