celecoxib oral

Additionally, PE#GOCNPs displayed anti-inflammatory properties by increasing IL10 and reducing pro-inflammatory cytokines more effectively than celecoxib...This novel approach has the potential to revolutionize the field of chemotherapy. Future studies should focus on the application of the encapsulated PE in various cancer cell lines, distinct gene expression factors, and cell cycles.

P2, N=18, Completed, University of Cologne | Recruiting --> Completed | N=26 --> 18 | Trial completion date: Dec 2023 --> Jun 2023 | Trial primary completion date: Dec 2023 --> Jun 2023

A novel series of pyrazole derivatives with urea/thiourea scaffolds 16a-l as hybrid sorafenib/erlotinib/celecoxib analogs was designed, synthesized and tested for its VEGFR-2, EGFRWT, EGFRT790M tyrosine kinases and COX-2, pro-inflammatory cytokines TNF-α and IL-6 inhibitory activities. Moreover, compounds 16a, 16c, 16d and 16 g had cell cycle arrest at G2/M phase with induced necrotic percentage compared to sorafenib of 2.06 %, 2.47 %, 1.57 %, 0.88 % and 1.83 % respectively. Amusingly, compounds 16a, 16c, 16d and 16 g inhibited VEGFR-2 with IC50 of 25 nM, 52 nM, 324 nM and 110 nM respectively, compared to sorafenib (IC50 = 85 nM), and had excellent EGFRWT and EGFRT790M kinase inhibitory activities (IC50 = 94 nM, 128 nM, 160 nM, 297 nM), (10 nM, 25 nM, 36 nM and 48 nM) respectively, compared to both erlotinib and osimertinib (IC50 = 114 nM, 56 nM) and (70 nM, 37 nM) respectively and showed (EGFRwt/EGFRT790M S.I.) of (range: 4.44-9.40) compared to erlotinib (2.03) and osmertinib (1.89).

Moreover, the synergistic effect of Ber improved the therapeutic potential of different drugs (paclitaxel (PTL), gemcitabine, dexamethasone, doxorubicin (DOX), and celecoxib) in different models. Various attempts could fabricate biologically active derivatives of Ber, such as 4-chlorobenzoyl berbamine (CBB) and O-4- ethoxyl-butyl-berbamine (EBB). The review focuses on the medicinal applications of Ber, particularly anti-cancer, cardioprotective, and anti-inflammatory, along with the mechanism of action.

P4, N=70, Recruiting, Northwell Health

Gain-of-function mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha gene (PIK3CA) is a significant factor in head and neck cancer (HNC). Salubrinal and N-acetyl-L-cysteine attenuated celecoxib-induced mitochondrial dysfunction. Collectively, our results suggest that celecoxib and SUS efficiently suppress activating PIK3CA mutation-harboring HNC progression by inducing ER and oxidative stress and mitochondrial dysfunction, leading to apoptotic cell death, further supporting NSAID treatment as a useful strategy for oncogenic PIK3CA-mutated HNC therapy.

We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.

Safety tests of repurposing drugs used in cancer therapy tested on C. elegans nematode indicated that CXB, FL, or their mixture at a concentration of up to 100 µM had no significant effect on the entire nematode organism up to 4th day of incubation. After a 7-day treatment, CXB significantly shortened the lifespan of C. elegans at 25-400 µM concentration and body length at 50-400 µM concentration.

First, the bromodomain-containing protein 4 (BRD4) inhibitor JQ1 and the cyclooxygenase-2 (COX-2) inhibitor celecoxib (CXB) were coloaded into chondroitin sulfate (CS) to obtain CS@JQ1/CXB nanoparticles (NPs). Combination treatment exhibited synergistic cytotoxicity, antimigration ability, and apoptosis-inducing and immune activation effects on TNBC cells and effectively suppressed tumor growth and metastasis in TNBC tumor-bearing mice by activating the tumor immune response and inhibiting angiogenesis. In summary, this study offers a novel combinatorial immunotherapeutic strategy for the clinical TNBC treatment.

P4, N=65, Completed, The University of Texas Health Science Center, Houston | Recruiting --> Completed | N=100 --> 65

The half maximal inhibitory concentration values for the most active compounds, 3d, 3e, and 4e towards COX-2 were 0.425, 0.519, and 0.356 µM, respectively, in comparison with celecoxib...The results of molecular modeling studies suggested that these compounds were characterized by a reasonable binding affinity toward the active site of COX-2, when compared to a reference ligand. These results might be taken into consideration in further investigations into new anti-inflammatory agents.

P2, N=60, Recruiting, Bateman Horne Center

This Phase 1 trial combined an hTERT-derived 7-peptide library, selected to ensure presentation by both HLA class-I and class-II in 90% of patients, with oral low-dose cyclophosphamide (to modulate Tregs) and the COX2 inhibitor celecoxib. This vaccine combination regimen was safe and associated with antigen-specific immunological responses. Clinical activity could be improved in future by combination with anti-PD1 checkpoint inhibition to address the emergence of an exhausted T cell population.

P3, N=600, Not yet recruiting, Xinqiao Hospital of Chongqing

MTT assays revealed the IC50 values of 245.69 ± 4.1 µM and 215.68 ± 3.8 µM on HepG2 and MCF7 cell lines, respectively, compared to the standard drug cisplatin (66.92 ± 1.8 µM and 46.83 ± 1.3 µM, respectively). The results suggest that sulfadiazine exhibited balanced inhibitory activity against the 5-LOX/COX-1 enzymes compared to the selective COX-2 inhibitor, celecoxib. These findings highlight the potential of sulfadiazine as a potential anticancer agent through balanced inhibitory activity against the COX/LOX pathway and reduction in the expression of inflammatory genes.

P2, N=60, Recruiting, Emory University | Trial completion date: Jan 2024 --> Feb 2025 | Trial primary completion date: Jan 2024 --> Feb 2025

P2, N=112, Recruiting, Sun Yat-sen University | Phase classification: P1/2 --> P2 | N=69 --> 112 | Trial completion date: May 2026 --> Apr 2030 | Trial primary completion date: May 2023 --> Apr 2027

P1, N=40, Completed, Centre Hospitalier Universitaire Vaudois | Active, not recruiting --> Completed | Trial completion date: Mar 2022 --> Oct 2023 | Trial primary completion date: Mar 2022 --> Oct 2023

P1, N=30, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial completion date: Dec 2023 --> Dec 2024

We previously reported that COX-2 upregulation induced by temozolomide (TMZ) supported chemoresistance...The presence of macrophages U937 within tumorspheres derived from GBM cell lines and primary cultures exposed to celecoxib (COX-2 inhibitor) with or without TMZ was studied by confocal microscopy...Remarkably, exogenous prostaglandin-E2 restored OPN and CD44, highlighting the COX-2 pivotal role in the protumor macrophages' state promotion. COX-2 inhibition interfered with TMZ's ability to induce M2-polarization and counteracted the development of an immunosuppressive TME.

P2, N=65, Recruiting, Children's Hospital of Eastern Ontario | Not yet recruiting --> Recruiting

P4, N=42, Completed, Charles University, Czech Republic | Recruiting --> Completed

P2, N=44, Recruiting, Sun Yat-sen University | Not yet recruiting --> Recruiting

All of the tested compounds showed cyclooxygenase (COX)-1 inhibitory effect more than celecoxib and less than indomethacin and also demonstrated an improved inhibitory activity against 15-lipoxygenase (15-LOX). The preferred binding affinity of these molecules was confirmed by docking studies. We conclude that arylidene-5(4H)-imidazolone scaffolds provide promising hits for developing new synthons with anti-inflammatory and antioxidant activities.

P1, N=15, Active, not recruiting, Baylor College of Medicine | Recruiting --> Active, not recruiting

To specifically curb the inflammation and alleviate immunosuppression, here, we developed a PGE2 inhibitor celecoxib (CXB)-loaded bionic nanoparticle (CP@CM) coated with activated murine vascular endothelial cell (C166 cells) membrane to target postoperative melanoma and inhibit its recurrence...Additionally, the immune responses were further enhanced by combining a PD-L1 monoclonal antibody. Ultimately, this immunotherapeutic strategy reversed the tumor immunosuppressive microenvironment and inhibited tumor recurrence, demonstrating a promising potential for postoperative immunotherapy for melanoma.

P1/2, N=12, Recruiting, Roswell Park Cancer Institute | Not yet recruiting --> Recruiting

P2, N=24, Recruiting, Roswell Park Cancer Institute | Suspended --> Recruiting

In this study, a universal extracellular-intracellular "on-demand" release nanomedicine DOX@PDA-ICG@MnO2@GN-CEL was developed for the combined fight against malignant tumors using a spatiotemporal controlled gelatin coated polydopamine (PDA@GN) as the carrier and loaded with the chemotherapeutic drug doxorubicin (DOX), the photosensitizer indocyanine green (ICG), the PDT enhancer MnO2 and the anti-inflammatory drug celecoxib (CEL) individually. PDA and ICG exhibited PTT synergistically, and DOX exerted chemotherapy with reduced chemotherapy resistance. The dual responsive drug release switch enabled the chemotherapeutic, photothermal, photodynamic and anti-inflammatory drugs precisely acted on different sites of tumor tissues and realized a promising multimodal combination therapy.

Our findings implicate NETs playing a critical role in the development of MASH-hepatic fibrosis by inducing metabolic reprogramming of HSCs via the TLR3/COX-2/PGE2 pathway. Therefore, NET inhibition may represent an attractive treatment target for MASH liver fibrosis.

TAN-secreted PGE2 upregulates IDO1, dampening T cell function in UBC. Celecoxib targeting of PGE2 synthesis represents a promising approach to enhance ICB efficacy in UBC.

P=N/A, N=10, Terminated, University of New Mexico | Completed --> Terminated; This was a Chart Review only and was entered in the system in error.

P1, N=12, Completed, Wright State University | Recruiting --> Completed | N=48 --> 12 | Trial completion date: Dec 2023 --> Mar 2023 | Trial primary completion date: Dec 2023 --> Mar 2023

High-dose DFMO is tolerable when added to chemotherapy in heavily pre-treated patients. A randomized Phase 2 trial of DFMO added to chemoimmunotherapy is ongoing [NCT03794349].

To conclude, the treatment protocol has the potential to induce cell cycle arrest, diminish the potentiality of cells for migration, and initiate apoptotic and autophagic cell death. Further research is recommended to unravel the potential antitumor effects of Abemaciclib/Celecoxib combination in different cancer types.

P1, N=60, Not yet recruiting, University of Pennsylvania | Trial completion date: May 2026 --> May 2028 | Trial primary completion date: May 2025 --> May 2026

Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, diclofenac, ibuprofen, or celecoxib have a well-established and unquestionable role in the human therapeutic arsenal, but still new perspectives are being discovered. It was also proved that neuroinflammation, with the involvement of NF-κB, PPARγ and the components of the UPR pathway has an essential impact on the development of central nervous system (CNS) diseases. Thus, it seems possible that these new molecular targets may expand the use of NSAIDs, e.g., in the treatment of cancers and/or CNS disorders.

It also resulted in a considerable decrease in ornithine decarboxylase (ODC) activity and the incorporation of [H]-thymidine into DNA. In addition, there was a significant improvement in histoarchitectural abnormalities such as epidermal thickness, number of epidermal cell layers, neutrophil infiltration, intercellular edema, and vasodilation. Our results demonstrates that topical celecoxib can reduce the inflammation, hyperproliferation, and hyperplasiogenic events of skin insults suggesting that it may prove to be a valuable management option for cutaneous lesion and associated illnesses such as atopic dermatitis, eczema, and psoriasis, as well as the emergence of non-melanoma cancer.

P1, N=12, Recruiting, Taipei Medical University Shuang Ho Hospital | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

ATPR and celecoxib inhibit the proliferation of cancer cells as well as induce apoptosis. Co-administration of ATPR and Cox-2 inhibitors has the potential to be a novel treatment plan for cancer.

Compounds 19c, 19f, 19h, 19 l exhibited COX-2 selectivity indexes in the range of 18.48 to 49.38 compared to celecoxib S.I. = 21.10), inhibit MCF-7 with IC = 9-16 μM compared to tamoxifen (IC = 27.9 μM). and showed good inhibitory activity against HEP-3B with IC = 4.5-14 μM compared to sorafenib (IC = 3.5 μM) (HEP-3B)...Compounds 19c, 19f, 19h, 19 l showed excellent inhibitory activity against A549 with IC = 3-4.5 μM compared to 5-FU with IC = 6 μM (A549). Compounds 19c, 19f, 19h, 19 l inhibit aromatase (IC of 22.40, 23.20, 22.70, 30.30 μM), EGFR (IC of 0.112, 0.205, 0.169 and 0.066 μM) and B-RAF (IC of 0.09, 0.06, 0.07 and 0.05 μM).

P2, N=29, Recruiting, Sun Yat-sen University | Not yet recruiting --> Recruiting