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Opposing roles of LTB4 and PGE2 in regulating the inflammasome-dependent scorpion venom-induced mortality.

Tityus serrulatus sting causes thousands of deaths annually worldwide. T. serrulatus-envenomed victims exhibit local or systemic reaction that culminates in pulmonary oedema, potentially leading to death. However, the molecular mechanisms underlying T. serrulatus venom (TsV) activity remain unknown. Here we show that TsV triggers NLRP3 inflammasome activation via K(+) efflux. Mechanistically, TsV triggers lung-resident cells to release PGE2, which induces IL-1β production via E prostanoid receptor 2/4-cAMP-PKA-NFκB-dependent mechanisms. IL-1β/IL-1R actions account for oedema and neutrophil rec

Curcumin in Autoimmune and Rheumatic Diseases.

Over recent decades, many clinical trials on curcumin supplementation have been conducted on various autoimmune diseases including osteoarthritis, type 2 diabetes, and ulcerative colitis patients. This review attempts to summarize the highlights from these clinical trials. The efficacy of curcumin either alone or in conjunction with existing treatment was evaluated. Sixteen clinical trials have been conducted in osteoarthritis, 14 of which yielded significant improvements in multiple disease parameters. Eight trials have been conducted in type 2 diabetes, all yielding significant improvement i

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… Patients were split into two groups, taking either 1000 mg curcumin-boswellia mixture daily or 200 mg celecoxib daily for 12 weeks. … NSAIDs such as celecoxib inhibit the inducible COX-2 isoenzyme, which modulates inflammation. …

Metastatic primary duodenal adeno-carcinoma responding to metronomic oral cyclophosphamide chemotherapy.

Primary adenocarcinoma of duodenum is a very rare tumour with a prevalence of only 0.3 to 1% of among all the tumours of gastrointestinal tracts. Localised tumours, if resected have good prognosis but those with metastates entails a poor prognosis, where generally palliation may be the only feasible option. Low dose continous cytotoxic treatment or metronomic chemotherapy prevents neoangiogenesis and chemoresistance thereby, provides excellent symptom relief and palliation in many advanced heavily pretreated solid malignancies. It offers as an affordable, less toxic therapy with moderate to go

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… The combination of cyclophosphamide with celecoxib for heavily pretreated gastrointestinal tumors is found to be feasible, well tolerated and associated with a promising antitumor activity both demonstrated by pharmacodynamic markers and clinical parameters.[ 14 ] The present patient presented with … extensive osteosclerotic bony metastasis with a novel metronomic chemobiological approach J Pediatr Hematol Oncol 2012 34 e195 8 22258352 10.1097/MPH.0b013e3182373e6a 13 Khan OA Blann AD Payne MJ Middleton MR Protheroe AS Talbot DC Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib …

Repurposing drugs in oncology (ReDO)-selective PDE5 inhibitors as anti-cancer agents.

Selective phosphodiesterase 5 inhibitors, including sildenafil, tadalafil and vardenafil, are widely-used in the treatment of erectile dysfunction and pulmonary arterial hypertension. They are also well-known as examples of successful drug repurposing in that they were initially developed for angina and only later developed for erectile dysfunction. However, these drugs may also be effective cancer treatments. A range of evidentiary sources are assessed in this paper and the case made that there is pre-clinical and clinical evidence that these drugs may offer clinical benefit in a range of can

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… | S | In vitro combination with celecoxib cytotoxic, in vivo combination with celecoxib increased survival [ 33 ]. | S | In vivo combination with local ablation reduced volume of tumour growth [ 34 ]. B-CLL | S, V | Both drugs induced apoptosis in 14 of 14 patient samples [ 14 ]. … Similarly, Booth et al . [ 96 ] have shown that sildenafil synergised with celecoxib or the celecoxib derivative OSU-03012 to increase cell death of a range of glioblastoma stem-like cells. …

Metronomic chemotherapy.

Toxic effects and chemoresistance are major hurdles in chemotherapy and to avoid these problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called "metronomic chemotherapy" has emerged. Such regimen involves the frequent administration of conventional chemotherapeutic agents at very low doses to target activated endothelial cells in tumors, the advantages of which include minimal adverse effects and a rare chance of developing acquired drug resistance. Previously it was thought that they act by targeting angiogenesis, but recently additional mechanism

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… These over-expressed genes are a new target of therapy and refractory multifocal pilocytic astrocytoma was treated with fluvastatin/celecoxib for 18 months successfully. … , and dexamethasone in advanced hormone-refractory prostate cancer Clin Cancer Res 2009 15 4954 62 19622584 10.1158/1078-0432.CCR-08-3317 26 Buckstein R Kerbel RS Shaked Y Nayar R Foden C Turner R High-Dose celecoxib and metronomic “low-dose” cyclophosphamide is an effective and safe therapy in patients …

The Role of Drug Repurposing in the Development of Novel Antimicrobial Drugs: Non-Antibiotic Pharmacological Agents as Quorum Sensing-Inhibitors.

Background: The emergence of multidrug-resistant organisms (MDROs) is a global public health issue, severely hindering clinicians in administering appropriate antimicrobial therapy. Drug repurposing is a drug development strategy, during which new pharmacological applications are identified for already approved drugs. From the viewpoint of the development of virulence inhibitors, inhibition of quorum sensing (QS) is a promising route because various important features in bacterial physiology and virulence are mediated by QS-dependent gene expression. Methods: Forty-five pharmacological agents,

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… In line with previous reports, ivermectin, celecoxib, and the azole-type antifungal agents were only effective against Gram-positive bacteria (in our case S. aureus ATCC 25923) [ 67 , 68 , 69 ]. … Repurposing celecoxib as a topical antimicrobial agent Front. Microbiol. 2015 6 750 10.3389/fmicb.2015.00750 26284040 PMC4517059 70. Kincses A. Varga B. Csonka Á. Sancha S. Mulhovo S. Madureira A.M. Ferreira M.-J.U. Spengler G. …

OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence.

PURPOSE: As a prelude to developing updated, evidence-based, international consensus recommendations for the management of hip and knee oste … al drug related adverse events such as GI toxicity with acetaminophen or myocardial infarction with celecoxib remained inconclusive. CONCLUSION: Twenty-three guidelines have been developed for the treatment of hip and/or knee OA, based on opinion alone, research evidence or both. Twenty of 51 modalities of therapy are universally recommended by these guide …

Wnt/β-catenin pathway regulates MGMT gene expression in cancer and inhibition of Wnt signalling prevents chemoresistance.

The DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is commonly overexpressed in cancers and is implicated in the development of chemoresistance. The use of drugs inhibiting MGMT has been hindered by their haematologic toxicity and inefficiency. As a different strategy to inhibit MGMT we investigated cellular regulators of MGMT expression in multiple cancers. Here we show a significant correlation between Wnt signalling and MGMT expression in cancers with different origin and confirm the findings by bioinformatic analysis and immunofluorescence. We demonstrate Wnt-dependent MGM

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges.

Uncontrolled inflammation is a salient factor in multiple chronic inflammatory diseases and cancers. In this review, we provided an in-depth analysis of the relationships and distinctions between uncontrolled inflammation, fibrosis and cancers, while emphasizing the challenges and opportunities of developing novel therapies for the treatment and/or management of these diseases. We described how drug delivery systems, combination therapy and the integration of tissue-targeted and/or pathways selective strategies could overcome the challenges of current agents for managing and/or treating chroni

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… However, in previous clinical trials, HER2 positive breast cancer patients that were treated with trastuzumab along with celecoxib did not experience improved efficacy [ 264 ]. … In a colorectal cancer chemoprevention study, cardiovascular risks (heart failure) was observed in patients taking a high daily dosage of celecoxib for a period of 3 years [ 265 ]. Another study has also noticed celecoxib’s cardiovascular risks [ 266 ]. …

Is Curcumin the Answer to Future Chemotherapy Cocktail?

The rise in cancer cases in recent years is an alarming situation worldwide. Despite the tremendous research and invention of new cancer therapies, the clinical outcomes are not always reassuring. Cancer cells could develop several evasive mechanisms for their survivability and render therapeutic failure. The continuous use of conventional cancer therapies leads to chemoresistance, and a higher dose of treatment results in even greater toxicities among cancer patients. Therefore, the search for an alternative treatment modality is crucial to break this viscous cycle. This paper explores the su

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… Lev-Ari et al. (2005) showed that the combined treatment of curcumin (15 μM) and celecoxib (25 μM) significantly reduced the cell proliferation and enhanced apoptotic effects in P-34 pancreatic cancer cells by suppressing COX-2 expression, as compared to celecoxib monotherapy [ 113 ]. … NCT00486460 | Phase III Trial of Gemcitabine, Curcumin and Celebrex in Patients With Advance or Inoperable Pancreatic Cancer | 3 | Pancreatic Cancer | Gemcitabine + Curcumin and/or Celecoxib | To evaluate gemcitabine in combination with curcumin and celecoxib for patients with pancreatic cancer. …

Immune Modulation in the Treatment of Amyotrophic Lateral Sclerosis: A Review of Clinical Trials.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of motor neurons. Though many molecular and genetic causes are thought to serve as predisposing or disease propagating factors, the underlying pathogenesis of the disease is not known. Recent discoveries have demonstrated the presence of inflammation propagating substrates in the central nervous system of patients afflicted with ALS. Over the past decade, this hypothesis has incited an effort to better understand the role of the immune system in ALS and has led to the trial of sever

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… Celecoxib Celecoxib, a cyclooxygenase-2 inhibitor (prostaglandin G/H synthase) is used to treat pain and inflammation; it also decreases the prostaglandin-induced release of glutamate. … Arch Neurol ( 1994 ) 51 : 861 – 4 . 10.1001/archneur.1994.00540210031010 8080385 49 Cudkowicz ME Shefner JM Schoenfeld DA Zhang H Andreasson KI Rothstein JD Trial of celecoxib in amyotrophic lateral sclerosis . …

Efficacy and Effectiveness of Carnitine Supplementation for Cancer-Related Fatigue: A Systematic Literature Review and Meta-Analysis.

BackgroundCarnitine deficiency has been implicated as a potential pathway for cancer-related fatigue that could be treated with carnitine supplementation. The aim of this systematic literature review and meta-analysis was to evaluate the literature regarding the use of supplemental carnitine as a treatment for cancer-related fatigue.MethodsUsing the PRISMA guidelines, an electronic search of the Cochrane Library, MEDLINE, Embase, CINAHL and reference lists was conducted. Data were extracted and independently assessed for quality using the Academy of Nutrition and Dietetics evidence analysis by

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… Maccio et al. [ 25 ] reported that a combination therapy that included carnitine (as well as celecoxib, alpha lipoic acid, carboxycysteine and megestrol acetate) resulted in a significantly improved CRF compared to the control group. … Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib +/− megestrol acetate for patients with cancer-related anorexia/cachexia syndrome Clin. Nutr. 2012 31 176 182 10.1016/j.clnu.2011.10.005 22047681 31. Graziano F. Bisonni R. Catalano V. Silva R. Rovidati S. …

Оценка раннего вмешательства в клинические испытания миеломы: систематический обзор.

КОЛИЧЕСТВО: Множественная миелома (ШМ), асимптоматическая прекурсорка множественной миеломы (ММ), сопряжена с различным риском продвижения к ММ. Существует мало консенсуса в отношении эффективности или оптимального времени лечения в рамках SMM. Мы систематически анализировали ландшафт всех клинических испытаний в ШММ. Мы сравнили эффективность методов лечения, изученных в рамках SMM, с результатами этих режимов, когда они использовались в недавно диагностированных миеломах (NDMM), с тем чтобы определить, свидетельствуют ли данные о более глубоких реакциях в рамках SMM и NDMM.МЕТОДЫ: Все возмож

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… Studies also had to evaluate potentially active myeloma drugs (including drugs considered to potentially be active but not proven, such as celecoxib and metformin) or bone-modifying agents; studies of other treatment types were excluded. … | Placebo | M-protein levels | NO | Celecoxib had no significant effect on the median monoclonal protein concentration, which went from a median of 1.44-1.65 g/dL with placebo and 2.42-2.24 g/dL with celecoxib ( P = .36) Lonial et al, 2020 14 | NCT01169337 | 182 | Parallel assignment, open label | Lenalidomide …

Targeted therapy in the treatment of malignant gliomas.

Malignant gliomas are invasive tumors with the potential to progress through current available therapies. These tumors are characterized by a number of abnormalities in molecular signaling that play roles in tumorigenesis, spread, and survival. These pathways are being actively investigated in both the pre-clinical and clinical settings as potential targets in the treatment of malignant gliomas. We will review many of the therapies that target the cancer cell, including the epidermal growth factor receptor, mammalian target of rapamycin, histone deacetylase, and farnesyl transferase. In additi

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… Selective inhibition of COX-2, using celecoxib (Celebrex ® , Pfizer) has been looked at extensively in a number of cancers including gliomas. In preclinical models of glioma the effect of celecoxib has been only modest. … Reardon DA Quinn JA Vredenburgh J Phase II trial of irinotecan plus celecoxib in adults with recurrent malignant glioma Cancer 2005 103 2 329 338 15558802 10.1002/cncr.20776 93. …

A technical note on emerging combination approach involved in the onconanotherapeutics.

Cancer is the second cause of mortality worldwide, and the currently available conventional treatment approach is associated with serious side effects and poor clinical outcomes. Based on the outcome of the exploratory preclinical and clinical studies, it was found that therapeutic response increases multiple folds when anticancer drugs are used in combination. However, the conventional combination of anticancer drugs was associated with various limitations such as increased cost of treatment, systemic toxicity, drug resistance, and reduced pharmacokinetic attributes. Hence, attempts were made

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… Considering these factors, a recent study designed a liposomal nanocarrier, encapsulated with celecoxib and genistein, due to their antitumoral properties. … Reactive oxygen species were not formed when cells were treated with empty liposomes (EL), celecoxib liposomes (CL) and genistein (GL), while a 3-fold rise in production of ROS was obtained in the cells subjected to celecoxib-genistein complex treatment. …

Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects.

The prognosis of patients with systemic lupus erythematosus has greatly improved since treatment regimens combining corticosteroids and immunosuppressive medications have been widely adopted in therapeutic strategies given to these patients. Immune suppression is evidently efficient but also leads to higher susceptibility to infectious and malignant diseases. Toxic effects and sometimes unexpectedly dramatic complications of current therapies have been progressively reported. Identifying novel molecular targets therefore remains an important issue in the treatment of lupus. The aim of this rev

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… . | [ 8 ] Celecoxib or celebrex | Cyclooxygenase-2 inhibition | Retrospective review of medical records for 50 patients treated with celecoxib. | Diminution of inflammation and good safety profile. | [ 10 ] | | Prospective trial including 51 patients. | Reduction of SLEDAI score and no increase of … Celecoxib for systemic lupus erythematosus: case series and literature review of the use of NSAIDs in SLE. Lupus. 2002;11:340–347. doi: 10.1191/0961203302lu204oa. Wallace DJ. Celecoxib for lupus. Arthritis Rheum. 2008;58:2923–2924. doi: 10.1002/art.23808. …

Safety and feasibility analysis of rapid daratumumab infusion in Chinese patients with multiple myeloma.

BackgroundWith the increasing use of daratumumab (DARA)-containing regimens for multiple myeloma (MM) patients in China, the standard infusion time of DARA is long, with the potential for infusion-related reactions (IRRs) and increased hospitalization and use of resources. Shortening the duration of DARA infusion helps to optimize the hospital stay and enhance the patient treatment experience. The current, commonly used 90-min rapid DARA infusion regimen may not be applicable to Chinese MM patients, and therefore, we explored a new 110-min rapid DARA infusion regimen aimed at reducing the trea

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… To prevent the occurrence of infusion‐related reactions, anti‐allergic drugs were used before both standard and rapid infusion of DARA, nonsteroidal anti‐inflammatory drugs (such as celecoxib) were added to the anti‐allergic drugs for the first infusion, and antihistamines (such as promethazine hydrochloride … The specific drugs used were as follows: 200 mg of celecoxib, 20 mg of dexamethasone, and 20 mg of diphenhydramine. TABLE 1 Daratumumab comparison of different infusion regimens. Abbreviation: h, hour. …

Revolutionizing ovarian cancer therapy by drug repositioning for accelerated and cost-effective treatments.

Drug repositioning, the practice of identifying novel applications for existing drugs beyond their originally intended medical indications, stands as a transformative strategy revolutionizing pharmaceutical productivity. In contrast to conventional drug development approaches, this innovative method has proven to be exceptionally effective. This is particularly relevant for cancer therapy, where the demand for groundbreaking treatments continues to grow. This review focuses on drug repositioning for ovarian cancer treatment, showcasing a comprehensive exploration grounded in thorough in vitro

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… Celecoxib effectively reduced PGE2 levels both in vitro (mesothelioma AB1 cell line) and in vivo (BALB/c mice) ( 267 ). … This difference was more pronounced at day 22 after tumor injection, and mice receiving the celecoxib diet did not exhibit any discernible side effects ( 267 ). These findings highlight the potential of celecoxib as an adjunctive therapy in cancer treatment strategies. …

Association of serum cyclooxygenase-2 levels with hand-foot syndrome in patients receiving capecitabine: an exploratory analysis of D-TORCH study.

BackgroundThe D-TORCH trial demonstrated superiority of 1% topical diclofenac over placebo in preventing capecitabine-induced hand-foot syndrome (HFS). We conducted an exploratory analysis of this study to assess the relationship between HFS and serum levels of the inflammatory marker, cyclooxygenase-2 (COX-2).MethodsSerum COX-2 levels were measured in patients in the D-TORCH study's experimental and placebo arms at baseline and 12 weeks of capecitabine-based therapy or at the development of HFS (whichever occurred earlier) and in 20 age-matched healthy controls using a human COX-2 ELISA kit (

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… Thus, celecoxib was explored to prevent capecitabine-associated HFS in a randomised controlled trial demonstrating a significant reduction in the incidence of capecitabine-associated HFS among patients with colorectal cancer [ 7 ]. … Serum dihydropyrimidine dehydrogenase levels were also found to be associated with grade 1 and 2 HFS among patients on celecoxib for prevention of capecitabine-induced HFS [ 7 ]. …

Induction of Pro-Apoptotic Endoplasmic Reticulum Stress in Multiple Myeloma Cells by NEO214, Perillyl Alcohol Conjugated to Rolipram.

Despite the introduction of new therapies for multiple myeloma (MM), many patients are still dying from this disease and novel treatments are urgently needed. We have designed a novel hybrid molecule, called NEO214, that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were investigated in a panel of MM cell lines. We found that NEO214 effectively killed MM cells in vitro with a potency that was over an order of

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… Aggravated endoplasmic reticulum stress as a basis for enhanced glioblastoma cell killing by bortezomib in combination with celecoxib or its non-coxib analogue, 2,5-dimethyl-celecoxib Cancer Res. 2008 68 8435 8441 10.1158/0008-5472.CAN-07-5555 18245486 15. Driessen C. Kraus M. Joerger M. Rosing H. … Downregulation of survivin expression and concomitant induction of apoptosis by celecoxib and its non-cyclooxygenase-2-inhibitory analog, dimethyl-celecoxib (DMC), in tumor cells in vitro and in vivo Mol. Cancer 2006 5 19 10.1186/1476-4598-5-19 16707021 PMC1479836 …