Tofacitinib and Risk of Malignancy: Results From the Safety of Tofacitinib in Routine Care Patients With Rheumatoid Arthritis (STAR‐RA) Study

Arthritis & Rheumatology, Journal Year: 2022, Volume and Issue: 74(10), P. 1648 - 1659

Published: May 29, 2022

Results of the ORAL Surveillance safety trial have indicated that there is an increased risk for development malignancies with tofacitinib therapy when compared to treatment tumor necrosis factor inhibitors (TNFi). This study was undertaken further examine this concern in rheumatoid arthritis (RA) patients a real-world setting.

Language: Английский

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Fisetin Deters Cell Proliferation, Induces Apoptosis, Alleviates Oxidative Stress and Inflammation in Human Cancer Cells, HeLa

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1707 - 1707

Published: Feb. 1, 2022

Fisetin, a flavonol profusely found in vegetables and fruits, exhibited myriad of properties preclinical studies to impede cancer growth.This study was proposed delineate molecular mechanisms through analysing the modulated expression various targets HeLa cells involved proliferation, apoptosis inflammation.MTT assay, flow cytometry, nuclear morphology, DNA fragmentation Annexin-Pi were performed evaluate anti-cancer potential fisetin. Furthermore, qPCR proteome profiler analyse variety gene related cell death, oxidative stress inflammation pathways.Fisetin demonstrated apoptotic inducing ability cells, which quite evident ladder pattern, decreased TMRE fluorescent intensity, cycle arrest at G2/M increased early late apoptosis. fisetin treatment pro-apoptotic genes such as APAF1, Bad, Bax, Bid BIK both transcript protein levels anti-apoptotic Bcl-2, BIRC8, MCL-1, XIAP/BIRC4, Livin/BIRC7, clap-2/BIRC3, etc. mitigate proliferation induce Interestingly, aforementioned alterations consequently led an elevated level Caspase-3, Caspase-8 Caspase-9, be consistent with expression. Moreover, downregulated AKT MAPK pathways avert enhance cells. Fisetin also improves alleviates by regulating JAK-STAT/NF-kB pathways.Together, these established that deters human cervical enhances ameliorates signalling may used therapeutic regime for better management.

Language: Английский

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Quercetin as a JAK–STAT inhibitor: a potential role in solid tumors and neurodegenerative diseases

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: July 26, 2022

Abstract The Janus kinase–signal transducer and activator of transcription (JAK–STAT) pathway is involved in many immunological processes, including cell growth, proliferation, differentiation, apoptosis, inflammatory responses. Some these processes can contribute to cancer progression neurodegeneration. Owing the complexity this its potential crosstalk with alternative pathways, monotherapy as targeted therapy has usually limited long-term efficacy. Currently, majority JAK–STAT-targeting drugs are still at preclinical stages. Meanwhile, a variety plant polyphenols, especially quercetin, exert their inhibitory effects on JAK–STAT through known unknown mechanisms. Quercetin shown prominent terms anti-inflammatory antitumor activity, well control neurodegenerative diseases. This review discusses pharmacological quercetin signaling solid tumors

Language: Английский

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An insight into the anticancer potentials of lignan arctiin: A comprehensive review of molecular mechanisms

Heliyon, Journal Year: 2024, Volume and Issue: 10(12), P. e32899 - e32899

Published: June 1, 2024

Natural products are being developed as possible treatment options due to the rising prevalence of cancer and harmful side effects synthetic medications. Arctiin is a naturally occurring lignan found in numerous plants exhibits different pharmacological activities, along with cancer. To elucidate anticancer properties underlying mechanisms action, comprehensive search various electronic databases was conducted using appropriate keywords identify relevant publications. The findings suggest that arctiin against tumor formation cancers such cervical, myeloma, prostate, endothelial, gastric, colon several preclinical investigations. This compound exerts its effect through cellular mechanisms, including mitochondrial dysfunction, cell cycle at phases (G2/M), inhibition proliferation, apoptotic death, cytotoxic effects, well migration invasion malignant cells. Moreover, study also revealed that, among pathways, shown be more potent terms PI3K/AKT JAK/STAT signaling pathways. However, pharmacokinetic investigation indicated compound's poor oral bioavailability. Because these findings, might considered promising chemotherapeutic drug candidate.

Language: Английский

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Location, location, location: Protein kinase nanoclustering for optimised signalling output

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Jan. 11, 2024

Protein kinases (PKs) are proteins at the core of cellular signalling and thereby responsible for most physiological processes their regulations. As all intracellular proteins, PKs subjected to Brownian thermal energy that tends homogenise distribution throughout volume cell. To access substrates perform critical functions, PK localisation is therefore tightly regulated in space time, relying upon a range clustering mechanisms. These include post-translational modifications, protein-protein protein-lipid interactions, as well liquid-liquid phase separation, allowing spatial restriction ultimately regulating substrates. In this review, we will focus on key mechanisms mediating nanoclustering pathophysiological processes. We propose nanoclusters act quantal unit output capable integration regulation time. specifically outline various super-resolution microscopy approaches currently used elucidate composition driving nanoscale explore pathological consequences altered kinase context neurodegenerative disorders, inflammation, cancer.

Language: Английский

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Quercetin exerts anti-tumor immune mechanism by regulating IL-6/JAK2/STAT3 signaling pathway to deplete Treg cells

Toxicon, Journal Year: 2024, Volume and Issue: 243, P. 107747 - 107747

Published: May 1, 2024

Language: Английский

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Molecular mechanisms underlying the regulation of tumour suppressor genes in lung cancer

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116275 - 116275

Published: Feb. 22, 2024

Tumour suppressor genes play a cardinal role in the development of large array human cancers, including lung cancer, which is one most frequently diagnosed cancers worldwide. Therefore, extensive studies have been committed to deciphering underlying mechanisms alterations tumour governing tumourigenesis, as well resistance cancer therapies. In spite encouraging clinical outcomes demonstrated by patients on initial treatment, subsequent unresponsiveness first-line treatments manifested virtually all inherently contentious issue. light aforementioned concerns, this review compiles current knowledge molecular some implicated that are either mutated and/or located chromosomal arms having high LOH rates (1p, 3p, 9p, 10q, 13q, and 17p). Our study identifies specific genomic loci prone LOH, revealing recurrent pattern cases. These loci, 3p14.2 (FHIT), 9p21.3 (p16

Language: Английский

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Precision Oncology, Signaling Pathways Reprogramming and Targeted Therapy: A Holistic Approach to Molecular Cancer Therapeutics

Published: Jan. 8, 2025

Cancer is a fatal genetic disease involving unregulated cell growth and proliferation with varying underlying complexities including immune evasion, treatment resistance recurrence, optimized required for proper cure. Molecular studies have revealed that tumors are extremely heterogeneous in nature, leading to the complexity of cancer development, which ultimately linked its machinery. It would require effective targeting dysregulated molecular mechanisms factors, regulatory proteins, adhesion molecules, molecules system mainly driven by alterations tumor suppressor genes oncogenes may vary among different types. Importantly, patients same type respond differently available treatments, indicating need patient-specific options. Thus, in-depth genomic patients’ needed fully understand determinants initiation progression targeted therapy. Precision oncology has evolved as form therapy focused on profiling identify involved manifestation tailored individualized disease. Accordingly, there been great developments formulation production anticancer agents recent years owing advances technologies enabling precise oncogenic pathways progression. This article aims briefly explain foundations frontiers precision context advancements tools techniques associated process assess scope importance realizing intended goals.

Language: Английский

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Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

Cancers, Journal Year: 2021, Volume and Issue: 13(11), P. 2730 - 2730

Published: May 31, 2021

Although great progress has been made in the treatment of cancer, search for new promising molecules with antitumor activity is still one greatest challenges fight against cancer due to increasing number cases each year. Chalcones (1,3-diphenyl-2-propen-1-one), precursors flavonoid synthesis higher plants, possess a wide spectrum biological activities including antimicrobial, anti-inflammatory, antioxidant, and anticancer. A plethora molecular mechanisms action have documented, induction apoptosis, autophagy, or other types cell death, cycle changes, modulation several signaling pathways associated survival death. In addition, blockade steps angiogenesis proteasome inhibition also documented. This review summarizes basic related antiproliferative effects chalcones, focusing on research articles from years January 2015–February 2021.

Language: Английский

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Silibinin Regulates Tumor Progression and Tumorsphere Formation by Suppressing PD-L1 Expression in Non-Small Cell Lung Cancer (NSCLC) Cells

Cells, Journal Year: 2021, Volume and Issue: 10(7), P. 1632 - 1632

Published: June 29, 2021

Recently, natural compounds have been used globally for cancer treatment studies. Silibinin is a compound extracted from Silybum marianum (milk thistle), which has suggested as an anticancer drug through various Studies on its activity in cancers are undergoing. This study demonstrated the molecular signaling behind of silibinin non-small cell lung (NSCLC). Quantitative real-time polymerase chain reaction and Western blotting analysis were performed analysis. Wound healing assay, invasion vitro angiogenesis silibinin. The results indicated that inhibited A549, H292, H460 proliferation concentration-dependent manner, confirmed by induction G0/G1 cycle arrest apoptosis inhibition tumor angiogenesis, migration, invasion. also assessed role suppressing tumorsphere formation using assay. By binding to epidermal growth factor receptor (EGFR), downregulated phosphorylated EGFR expression, then downstream targets, JAK2/STAT5 PI3K/AKT pathways, thereby reduced matrix metalloproteinase, PD-L1, vascular endothelial expression. Binding STAT5 binds PD-L1 promoter region nucleus STAT5/PD-L1 complex. Altogether, could be considered candidate immunotherapy stem cell-targeted therapy.

Language: Английский

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