Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticancer and antiinflammatory agents

Frontiers in Chemistry, Journal Year: 2024, Volume and Issue: 12

Published: March 18, 2024

Introduction: Cancer, a significant global health concern, necessitates innovative treatments. The pivotal role of chronic inflammation in cancer development underscores the urgency for novel therapeutic strategies. Benzothiazole derivatives exhibit promise due to their distinctive structures and broad spectrum biological effects. This study aims explore new anti-tumor small molecule drugs that simultaneously anti-inflammatory anticancer based on advantages benzothiazole frameworks. Methods: compounds were characterized by nuclear magnetic resonance (NMR), liquid chromatograph-mass spectrometer (LC-MS) high performance chromatography (HPLC) structure as well purity other related physicochemical properties. effects proliferation human epidermoid carcinoma cell line (A431) non-small lung lines (A549, H1299) evaluated MTT method. effect expression levels inflammatory factors IL-6 TNF-α mouse monocyte macrophages (RAW264.7) was assessed using enzyme-linked immunosorbent assay (ELISA). apoptosis cycle A431 A549 cells flow cytometry. migration scratch wound healing assay. protein Western Blot parameters, pharmacokinetic properties, toxicity drug similarity active compound predicted Swiss ADME admetSAR web servers. Results: Twenty-five designed synthesized, with confirmed through spectrogram verification. 6-chloro- N -(4-nitrobenzyl) benzo[d] thiazol-2-amine (compound B7 ) screened series bioactivity assessments, which significantly inhibited A431, H1299 cells, decreased activity TNF-α, hindered migration. In addition, at concentrations 1, 2, 4 μM, exhibited apoptosis-promoting cycle-arresting similar those lead 7-chloro- -(2, 6-dichlorophenyl) thiazole-2-amine 4i ). blot analysis both AKT ERK signaling pathways cells. prediction results ADMET indicated had good Discussion: has innovatively developed derivatives, focus its notable dual activities. stands out ability reduce A549, lower cytokines TNF-α. These position promising candidate dual-action therapy. study’s mechanistic exploration, highlighting ’s simultaneous inhibition pathways, offers strategy addressing survival mechanisms tumor milieu facilitating progression.

Language: Английский

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Global research trends and emerging hotspots in nano-drug delivery systems for lung cancer: a comprehensive bibliometric analysis (1998–2024)

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 11, 2025

Nano-drug delivery systems (NDDS) have become a promising alternative and adjunctive strategy for lung cancer (LC) treatment. However, comprehensive bibliometric analyses examining global research efforts on NDDS in LC are scarce. This study aims to fill this gap by identifying key trends, emerging hotspots, collaboration networks within the field of LC. A total 2452 publications, spanning from 1998 2024, were extracted Web Science Core Collection. The data analyzed using tools such as VOSviewer, CiteSpace, R package 'bibliometrix'. analysis covered contributions 12,539 researchers affiliated with 2689 institutions across 55 countries, their work published 551 different journals. Research output has increased steadily, China United States leading both publication volume impact. Major contributors include Chinese Academy Sciences Shanghai Jiao Tong University. International Journal Nanomedicine most articles, while Controlled Release ranked highest co-citations. Kamal Dua authored papers, Maeda, H. was frequently co-cited author. Key areas encompass "active targeting", "drug optimization", "overcoming drug resistance", "nanocarriers", "pulmonary delivery". Emerging hotspots "epithelial mesenchymal transition", "mucus penetration", "lipid nanoparticles", "hydrogels", "immune checkpoint inhibitors". analysis, first LC, identifies targeting" nanoparticles" These findings provide essential insights guide future optimize treatment strategies.

Language: Английский

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Immune-related adverse events with PD-1/PD-L1 inhibitors: insights from a real-world cohort of 2523 patients

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 31, 2025

Immune checkpoint inhibitors (ICIs) have significantly changed cancer therapy, improving patient survival rates and clinical outcomes. Nevertheless, the use of PD-1/PD-L1 can result in immune-related adverse events (irAEs). This study aims to investigate prevalence associated risk factors irAEs a real-world setting, as well assess their effects on optimal therapeutic A retrospective analysis involved 2523 patients with who received inpatient treatment between January 2018 December 2022. We documented patients' demographic characteristics, PD-1 or PD-L1 inhibitors, modalities, incidences, timing, severity irAEs, efficacy outcomes by reviewing records. Patients were categorized into an group non-irAEs group, former further subdivided multiple single irAE group. Chi-square tests employed evaluate differences baseline characteristics groups, groups. Additionally, logistic regression was utilized identify linked irAEs. Among eligible patients, 1096 reported 1802 incidence 43.4%. individuals, 92.1% classified grade 1-2, while 7.9% 3 higher. IrAEs affected various organ systems, endocrine toxicity (17.7%), hepatic (17.2%), hematologic (11.4%) being most common. 20.5% experienced multi-system The average time for develop within four cycles. Significant gender, age, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), comorbidities, modalities observed but not Compared exhibited higher objective response rate (ORR) disease control (DCR), also showed ORR than indicated that occurrence is related ECOG PS, modalities. may be better benefits.

Language: Английский

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Recent Developments in the Management of Renal Cell Cancer

JCO Oncology Practice, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

The management of renal cell carcinoma (RCC) has seen significant advancements in recent years with the introduction novel therapeutic agents and combination regimens. Immune checkpoint inhibitors (ICIs) have revolutionized treatment landscape, particularly for advanced metastatic RCC, where ICI-based combinations shown substantial improvements survival outcomes. Dual immunotherapy combinations, such as nivolumab plus ipilimumab, ICI-vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) including pembrolizumab axitinib, cabozantinib, lenvatinib, demonstrated overall (OS) benefits first-line treatment, redefining standard care RCC. Adjuvant is also approved resected high-risk RCC only adjuvant therapy that prolongs OS Additionally, development belzutifan, a hypoxia-inducible factor-2 alpha inhibitor, offers new option patients whose disease progresses after ICI VEGF TKI therapies. Recent results from CONTACT-3 TiNiVo-2 confirm rechallenge should be generally discouraged. This review provides detailed overview current evidence supporting immune-based well insights into sequencing strategies

Language: Английский

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Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors and CAR-T Cell Therapy: A Comprehensive Imaging-Based Review

Cancers, Journal Year: 2024, Volume and Issue: 16(14), P. 2585 - 2585

Published: July 19, 2024

Immunotherapy has revolutionized oncology care, improving patient outcomes in several cancers. However, these therapies are also associated with typical immune-related adverse events due to the enhanced inflammatory and immune response. These toxicities can arise at any time during treatment but more frequent within first few months. Any organ tissue be affected, ranging from mild life-threatening. While some manifestations common often mild, such as dermatitis colitis, others rarer severe, myocarditis. Management depends on severity, being held for >grade 2 toxicities. Steroids used severe cases, immunosuppressive may considered non-responsive toxicities, along specific support. A multidisciplinary approach is mandatory prompt identification management. The diagnosis primarily of exclusion. It relies imaging features, and, when possible, cytologic and/or pathological analyses performed confirmation. In case clinical suspicion, required assess presence, extent, features abnormalities evoke rule out differential diagnoses. This imaging-based review illustrates diverse system-specific checkpoint inhibitors chimeric antigen receptor T-cells a perspective. Clinical characteristics, cytological histological patterns, well management approach, presented insights into radiological tips distinguish most important diagnoses mimickers—including tumor progression, pseudoprogression, inflammation, infection—to guide specialists pathway diagnosing events.

Language: Английский

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TRAIL agonists rescue mice from radiation-induced lung, skin or esophageal injury

Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Radiotherapy can be limited by pneumonitis which is impacted innate immunity, including pathways regulated TRAIL death receptor DR5. We investigated whether DR5 agonists could rescue mice from toxic effects of radiation and found two different agonists, parenteral PEGylated trimeric-TRAIL (TLY012) oral TRAIL-Inducing Compound (TIC10/ONC201) reduce pneumonitis, alveolar-wall thickness, oxygen desaturation. Lung protection extended to late less fibrosis at 22-weeks in TLY012-rescued survivors versus un-rescued surviving irradiated-mice. Wild-type orthotopic breast tumor-bearing receiving 20-Gy thoracic were protected with disappearance tumors. At the molecular level, radioprotection appeared due inhibition CCL22, a macrophage-derived chemokine previously associated pulmonary fibrosis. Treatment anti-CCL22 reduced lung injury vivo but so than TLY012. Pneumonitis severity was worse female male mice, this increased expression X-linked TLR7. Irradiated had esophagitis characterized epithelial disruption muscularis externa thickness following treatment ONC201 analogue ONC212. The discovery that short-term pathway effectively rescues animals dermatitis high doses exposure has important translational implications.

Language: Английский

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Acute respiratory distress syndrome (ARDS): from mechanistic insights to therapeutic strategies

MedComm, Journal Year: 2025, Volume and Issue: 6(2)

Published: Jan. 26, 2025

Abstract Acute respiratory distress syndrome (ARDS) is a clinical of acute hypoxic failure caused by diffuse lung inflammation and edema. ARDS can be precipitated intrapulmonary factors or extrapulmonary factors, which lead to severe hypoxemia. Patients suffering from have high mortality rates, including 28‐day rate 34.8% an overall in‐hospital 40.0%. The pathophysiology complex involves the activation dysregulation multiple overlapping interacting pathways systemic coagulation, system, circulatory immune system. In general, treatment inflammatory injuries coordinated process that downregulation proinflammatory upregulation anti‐inflammatory pathways. Given complexity underlying disease, needs tailored problem. Hence, we discuss pathogenesis methods affected organs, 2019 coronavirus disease (COVID‐19)‐related pneumonia, drowning, trauma, blood transfusion, pancreatitis, sepsis. This review intended provide new perspective concerning offer novel insight into future therapeutic interventions.

Language: Английский

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Late-onset recurrent immune checkpoint inhibitor-related pneumonitis after cessation of pembrolizumab: a case report

Immunotherapy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 4

Published: April 2, 2025

Immune-related adverse events typically occur during the early phases of immune checkpoint inhibitor therapy. However, late-onset immune-related can still arise long after therapy has ended. Immune inhibitor-related pneumonitis warrants special attention for risk assessment and detection due to its potential serious outcomes, including hospitalization death. Despite rarity, should be considered in differential diagnosis dyspnea patients with a history prevent morbidity mortality. In this case report, we present an 84-year-old female patient suffering from locally advanced triple-negative breast cancer requiring 104 days last cycle pembrolizumab. Following successful treatment corticosteroids, recurrence occurred month later. Corticosteroid was reinitiated, gradually tapered radiological improvement, eventually discontinued. The remains remission cancer. For therapy, medical vigilance, accurate diagnosis, timely management are crucial.

Language: Английский

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Advancing the understanding of the role of apoptosis in lung cancer immunotherapy: Global research trends, key themes, and emerging frontiers

Human Vaccines & Immunotherapeutics, Journal Year: 2025, Volume and Issue: 21(1)

Published: April 5, 2025

Apoptosis is vital for improving the efficacy of lung cancer (LC) immunotherapy by targeting cell elimination. Despite its importance, there a lack comprehensive bibliometric studies analyzing global research on apoptosis in LC immunotherapy. This analysis aims to address this gap highlighting key trends, contributors, and future directions. A total 969 publications from 1996 2024 were extracted Web Science Core Collection. Analysis was conducted using VOSviewer, CiteSpace, R package 'bibliometrix.' The study included contributions 6,894 researchers across 1,469 institutions 61 countries, with published 356 journals. volume has steadily increased, led China United States, Sichuan University as top contributor. journal Cancers most articles, while Cancer Research had highest co-citations. Yu-Quan Wei leading author, Jemal, A. frequently co-cited. Key themes include "cell death mechanisms," "immune regulation," "combination therapies," "gene nanomedicine applications," "traditional Chinese medicine (TCM)." Future likely focus "coordinated regulation multiple pathways," "modulation tumor immune microenvironment," "optimization combination "novel strategies gene "integration TCM" personalized treatment. first role immunotherapy, providing an landscape patterns emerging therapeutic strategies. findings offer insights guide optimize treatment approaches.

Language: Английский

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Unveiling hypoxia-related prognostic and immunotherapeutic biomarkers in lung adenocarcinoma through single-cell and bulk RNA sequencing: Including insights into PGF

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 309, P. 143056 - 143056

Published: April 12, 2025

Language: Английский

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