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Opioids compared to placebo or other treatments for chronic low-back pain.

BACKGROUND: The use of opioids in the long-term management of chronic low-back pain (CLBP) has increased dramatically. Despite this trend, t … e). One trial (1583 participants) demonstrated that tramadol may make little difference compared to celecoxib (RR 0.82, 95% CI 0.76 to 0.90; very low quality evidence) for pain relief. Two trials (272 participants) found no difference between opioids and antidepressants for either pain (SMD 0.21, 95% CI -0.03 to 0.45; very low quality evidence), or function …

RETRACTED: Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are the backbone of osteoarthritis pain management. We aimed to assess the effect … as drug dose increased, but corresponding tests for a linear dose effect were significant only for celecoxib (p=0·030), diclofenac (p=0·031), and naproxen (p=0·026). We found no evidence that treatment effects varied over the duration of treatment. Model fit was good, and between-trial heterogeneity and inconsistency were low in all analyses. All trials we …

Epidemiology of non-steroidal anti-inflammatory drugs and cancer.

There is evidence that aspirin--and apparently other NSAIDs--may be protective agents against cancer in the gastrointestinal tract. These effects are particularly well documented in the colon and rectum. Even considered in isolation, the observational data regarding colorectal neoplasia are quite strong, and the reality of a protective effect is buttressed by clinical trial data showing that aspirin prevents sporadic adenomas. Furthermore, the NSAIDs sulindac celecoxib have actually led to the regression of existing colorectal polyps in patients with FAP. Clearly, NSAIDs have the potential to …

Small-molecule inducers of Aβ-42 peptide production share a common mechanism of action.

The pathways leading specifically to the toxic Aβ42 peptide production, a key event in Alzheimer's disease (AD), are unknown. While searching for pathways that mediate pathological increases of Aβ42, we identified Aftin-4, a new compound that selectively and potently increases Aβ42 compared to DMSO (N2a cells: 7-fold; primary neurons: 4-fold; brain lysates: 2-fold) with an EC(50) of 30 μM. These results were confirmed by ELISA and IP-WB. Using affinity chromatography and mass spectrometry, we identified 3 proteins (VDAC1, prohibitin, and mitofilin) relevant to AD that interact with Aftin-4, bu

Anti-inflammatory drugs in the 21st century.

Historically, anti-inflammatory drugs had their origins in the serendipitous discovery of certain plants and their extracts being applied fo … velopment following the introduction of two new highly selective COX-2 inhibitors, known as coxibs (celecoxib and rofecoxib) which were claimed to have low GI side effects. While found to have fulfilled these aims in part, an alarming turn of events took place in the late 2004 period when rofecoxib was withdrawn worldwide because of serious cardiovascular e …

Anti-Inflammatory Drugs as Anticancer Agents.

Inflammation is strictly associated with cancer and plays a key role in tumor development and progression. Several epidemiological studies have demonstrated that inflammation can predispose to tumors, therefore targeting inflammation and the molecules involved in the inflammatory process could represent a good strategy for cancer prevention and therapy. In the past, several clinical studies have demonstrated that many anti-inflammatory agents, including non-steroidal anti-inflammatory drugs (NSAIDs), are able to interfere with the tumor microenvironment by reducing cell migration and increasin

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… Clinical studies demonstrated that FAP patients that used a specific COX-2 inhibitor, celecoxib, displayed regression of existing adenomas [ 124 ]. On this basis, celecoxib was approved by the FDA for the use in the adjuvant therapy of FAP [ 101 ]. … In particular, celecoxib in combination with irinotecan or doxorubicin induced tumor growth inhibition in rats models of neuroblastoma [ 103 ]. Moreover, celecoxib increased the response of prostate cancer cells to docetaxel in vitro and in vivo and sensitized gliomas to radiation [ 143 ]. …

Immunotherapy of Hematological Malignancies of Human B-Cell Origin with CD19 CAR T Lymphocytes.

Acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) are hematological malignancies with high incidence rates that respond relatively well to conventional therapies. However, a major issue is the clinical emergence of patients with relapsed or refractory (r/r) NHL or ALL. In such circumstances, opportunities for complete remission significantly decline and mortality rates increase. The recent FDA approval of multiple cell-based therapies, Kymriah (tisagenlecleucel), Yescarta (axicabtagene ciloleucel), Tecartus (Brexucabtagene autoleucel KTE-X19), and Breyanzi (Lisocabtagene Mara

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… Celecoxib Celecoxib-induced apoptosis is mediated via the intrinsic apoptotic signaling pathway, which is Bcl-2 independent but apoptosome-dependent. … Celecoxib-induced apoptosis requires Apaf-1 and pro-caspase-9 in Jurkat T lymphoma cells, but the absence of Bcl-2 has no effect on apoptosis induced by celecoxib. …

Exploring COX-Independent Pathways: A Novel Approach for Meloxicam and Other NSAIDs in Cancer and Cardiovascular Disease Treatment.

As a fundamental process of innate immunity, inflammation is associated with the pathologic process of various diseases and constitutes a prevalent risk factor for both cancer and cardiovascular disease (CVD). Studies have indicated that several non-steroidal anti-inflammatory drugs (NSAIDs), including Meloxicam, may prevent tumorigenesis, reduce the risk of carcinogenesis, improve the efficacy of anticancer therapies, and reduce the risk of CVD, in addition to controlling the body's inflammatory imbalances. Traditionally, most NSAIDs work by inhibiting cyclooxygenase (COX) activity, thereby b

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… Conversely, Celecoxib and Sulindac inhibit SIRT1 expression, thereby reducing the migration and invasion of lung cancer cells [ 44 ]. … Celecoxib also inhibits ERK phosphorylation while enhancing p38 and JNK signaling, leading to reduced cell growth and increased apoptosis [ 57 , 130 , 131 ]. …

Targeting inflammation as cancer therapy.

Inflammation has accompanied human beings since the emergence of wounds and infections. In the past decades, numerous efforts have been undertaken to explore the potential role of inflammation in cancer, from tumor development, invasion, and metastasis to the resistance of tumors to treatment. Inflammation-targeted agents not only demonstrate the potential to suppress cancer development, but also to improve the efficacy of other therapeutic modalities. In this review, we describe the highly dynamic and complex inflammatory tumor microenvironment, with discussion on key inflammation mediators i

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… with ERBB2-negative breast cancer | Lung cancer | Celecoxib + chemotherapy/RT/anti-EGFR TKIs | NCT00300729 , NCT01503385 | Celecoxib at a maximal tolerated dose of 800 mg/d can be safely administered concurrently with thoracic radiotherapy of NSCLC | CRC | Celecoxib + cetuximab/chemotherapy (FOLFIRI … In other phase II trials however, celecoxib treatment ( NCT00300729 ) or adding celecoxib to concurrent chemoradiation ( NCT01503385 ) did not improve survival of NSCLC patients [ 294 , 295 ]. …

Single dose oral analgesics for acute postoperative pain in adults - an overview of Cochrane reviews.

BACKGROUND: This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy … etoricoxib 120 mg, diflunisal 500 mg, paracetamol 650 mg plus oxycodone 10 mg, naproxen 500/550 mg, celecoxib 400 mg, and ibuprofen 400 mg plus paracetamol 1000 mg.There was no evidence of analgesic effect for aceclofenac 150 mg, aspirin 500 mg, and oxycodone 5 mg (low quality evidence). No trial data were available in reviews of acemetacin, meloxicam, nabu …

Chemoprevention of bladder cancer.

The data presented herein, although highly supportive for a protective role of various nutrients against bladder cancer, are far from defini … est promise and can freely be recommended to patients. For synthetically synthesized agents such as celecoxib, piroxicam, or DFMO, recommendations must be deferred until the results of clinical trials are conclusively in favor of their use. Many of the dietary factors found to be protective against bladder cancer are being investigated in other cancers and …

Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgen

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… While, in the clinical trial NCT00068432 , the authors concluded that the combination of gemcitabine and celecoxib was beneficial compared to gemcitabine individually, in the NCT00176813 trial, the combination of celecoxib with gemcitabine and cisplatin did not reveal a significant impact on the survival … The potential adjuvant anticancer effect of celecoxib is also being evaluated in another clinical trial ( NCT01111591 ) [ 230 ]. …

Which Interventions Are Effective in Treating Sleep Disturbances After THA or TKA? A Systematic Review.

BACKGROUND: Poor sleep quality is a common complaint after total joint arthroplasty (TJA), and it is associated with reports of higher pain … 04 over concerns about increased risk of cardiovascular events. Another cyclooxygenase-2 inhibitor, celecoxib, remains available. No other intervention demonstrated a clinical benefit. Side effects of melatonin include dizziness, headache, paresthesia, and nausea, and it is contraindicated in patients with liver failure, autoimmune conditions, or who are re …

Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent.

Diclofenac (DCF) is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID), with a range of actions which are of interest in an oncological context. While there has long been an interest in the use of NSAIDs in chemoprevention, there is now emerging evidence that such drugs may have activity in a treatment setting. DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism. Both pre-clinical and clinical evidence of these effects, in mul

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… In vitro DCF and the selective COX-2 inhibitor celecoxib inhibited cell growth in a panel of neuroblastoma cell lines. The IC50 ranged from 12.5 to 50 μM for celecoxib and 100 to 600 μM for DCF, with evidence of increased apoptosis in response to DCF. … The celecoxib dose used was 30 mg/kg/d, which the authors reported as equivalent to a human dose of 400 mg/day, which is a clinically relevant dose. …

Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?

Drug repurposing is the use of known drugs for new indications. Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. So far, few treatments have been approved in this disease. However, its incidence is expected to increase significantly, particularly in developing countries. Consequently, drug repurposing appears as an attractive strategy for drug development in MPM, since the known pharmacology and safety profile based on previous approvals of repurposed drugs allows for faster time-to-market for patients and lower treatment cost. This is critical in low- and middle-in

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… In MPM, celecoxib was shown to reduce prostaglandin E2 levels in AB1, a murine MPM cell line [ 73 ]. The impact of COX-2 inhibition by celecoxib has been evaluated in vivo in BALB/c mice xenografted with AB1 cells. … Consequently, combining dendritic cells (DC)-based immunotherapy with celecoxib in MPM improved survival (p=0.027), compared to a single treatment with celecoxib (p=0.305) or DC-based immunotherapy (p=0.456). Clinical assessment of the role of COX-2 in MPM is missing. …

Nonsteroidal anti-inflammatory drugs for dysmenorrhoea.

BACKGROUND: Dysmenorrhoea is a common gynaecological problem consisting of painful cramps accompanying menstruation, which in the absence of … ecific selectorsOnly two of the included studies utilised COX-2-specific inhibitors (etoricoxib and celecoxib). There was no evidence that COX-2-specific inhibitors were more effective or tolerable for the treatment of dysmenorrhoea than traditional NSAIDs; however data were very scanty. NSAIDs versus paracetamolNSAIDs appeared to be more effective for pain …

Some Aspects and Convergence of Human and Veterinary Drug Repositioning.

Drug innovation traditionally follows a de novo approach with new molecules through a complex preclinical and clinical pathway. In addition to this strategy, drug repositioning has also become an important complementary approach, which can be shorter, cheaper, and less risky. This review provides an overview of drug innovation in both human and veterinary medicine, with a focus on drug repositioning. The evolution of drug repositioning and the effectiveness of this approach are presented, including the growing role of data science and computational modeling methods in identifying drugs with po

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… Similarly, Seo et al. [ 222 ] examined the effects of celecoxib on canine melanoma cell lines, finding it induced cell cycle arrest and apoptosis, especially in cells with high COX-2 expression. They found that celecoxib caused G0/G1 phase arrest and activated caspase-3. … Saito et al. [ 224 ] investigated COX-2 inhibitors (meloxicam, etodolac, celecoxib) in canine mammary tumor cells. All inhibitors suppressed cell growth, and etodolac and celecoxib were particularly effective in inducing apoptosis via the mitochondrial pathway. …

Dual COX-2/TNF-α Inhibitors as Promising Anti-inflammatory and Cancer Chemopreventive Agents: A Review.

Cyclooxygenases (COX) play a pivotal role in inflammation and are responsible for the production of prostaglandins (PGs). Two types of COXs have been identified as key biological targets for drug design: Constitutive COX-1 and inducible COX-2. Nonsteroidal anti-inflammatory drugs (NSAIDs) target COX-1, while selective COX-2 inhibitors are designed for COX-2. These COX isoforms are involved in multiple physiological and pathological pathways throughout the body. Overproduction of tumor necrosis factor-alpha (TNF-α) plays a role in COX-2's inflammatory activity. Tumor necrosis factor-alpha can c

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… Among the newly synthesized analogs, compounds 3 and 4 ( Figure 7 ) demonstrated superior anti-inflammatory properties and caused fewer gastric ulcers compared to celecoxib. Additionally, they effectively inhibited PGE2 production to a greater extent than celecoxib. … This specific structure confers celecoxib its selective inhibitory action against COX-2, distinguishing it from non-selective NSAIDs. …

Metronomic chemotherapy: changing the paradigm that more is better.

The introduction of the "maximum tolerated dose" in usual treatment protocols (and its concomitant overt toxicity) made necessary the imposition of rest periods between cycles of therapy-a practice that not only involves re-growth of tumour cells, but also growth of selected clones resistant to the therapy. To avoid the problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called "metronomic chemotherapy" has been proposed. This name makes reference to the chronic, equally spaced administration of (generally) low doses of various chemotherapeutic drugs

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… Also, in a phase ii study of mct with etoposide and cyclophosphamide in combination with daily thalidomide and celecoxib for recurrent malignant gliomas in adults, the serum and urine levels of vegf , b fgf , endostatin, and tsp -1 were evaluated. … A phase ii trial of continuous low-dose oral cyclophosphamide and celecoxib in patients with renal cell carcinoma. Cancer Chemother Pharmacol. 2007;60:135–41. doi: 10.1007/s00280-006-0347-x. 87. Bocci G, Tuccori M, Emmenegger U, et al. …

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience.

Metronomic chemotherapy, continuous and dose-dense administration of chemotherapeutic drugs with lowered doses, is being evaluated for substituting, augmenting, or appending conventional maximum tolerated dose regimens, with preclinical and clinical studies for the past few decades. To date, the principle mechanisms of its action include impeding tumoral angiogenesis and modulation of hosts' immune system, affecting directly tumor cells, their progenitors, and neighboring stromal cells. Its better toxicity profile, lower cost, and easier use are main advantages over conventional therapies. The

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… Celecoxib was joined with carboplatin by Legge et al. Median PFS and OS were 5 and 13 months, respectively [ 152 ]. … A similar study with TMZ and celecoxib in refractory GBM patients resulted in a PFS of 6 months in 43% of patients [ 166 ]. …