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Celecoxib is a selective cyclooxygenase-2 inhibitor. Accordingly, it has similar properties as the non-selective nonsteroidal anti-inflammatory drugs (NSAID) but it shows less gastro-toxicity. However, a problem observed with this drug is an increase in cardiovascular adverse events. Today, celecoxib is still on the market because it has real painkiller and anti-inflammatory properties and there is no absolute evidence about the cardiovascular toxicity. Furthermore, it may exert an anti-proliferative activity through a variety of mechanisms My MS these will focus on these mechanisms, and more specifically in the context of the familial adenomatous polyposis disease and the colorectal cancer. After a description of the cyclooxygenase system and the major pharmacological properties of the celecoxib, I will discuss the cardiovascular effects of COXIBs and propose my view on the future of this molecule Le celecoxib est un inhibiteur sélectif de la cyclo-oxygénase 2. Il présente, dès lors, des propriétés semblables aux AINS (anti-inflammatoires non-stéroïdiens) non-sélectifs tout en évitant un de leur problème majeur, la toxicité gastrique. Cependant, la toxicité cardiovasculaire de cette classe médicamenteuse a été un frein à son développement. Actuellement, le celecoxib survit au sein de sa classe et ce par ses propriétés analgésiques et anti-inflammatoires confirmées et l’absence de preuves indiscutables au niveau de la toxicité cardiovasculaire. De plus, il présente une activité s’opposant au développement cancéreux par divers mécanismes. Mon mémoire repose sur l’explication de ces mécanismes, et ce plus particulièrement dans la cadre de la polypose adénomateuse familiale et du cancer colorectal. Après avoir explicité le fonctionnement basique des inhibiteurs de cyclo-oxygénases et avoir développé la pharmacologie et la pharmacocinétique du celecoxib, j’aborderai également al polémique autour de la problématique cardiovasculaire des COXIBs et tenterai de trancher sur l’utilité future de cette molécule controversée.

celecoxib --- Colorectal Neoplasms --- Cyclooxygenase 2 Inhibitors

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This Statistical Brief uses data from the Household Component of the Medical Expenditure Panel Survey (MEPS-HC) to document trends in use and expenditures for COX-2 inhibitors from 1997 to 2003 in relation to trends for traditional NSAIDS.

Nonsteroidal anti-inflammatory agents. --- Cyclooxygenase 2 --- Inhibitors.

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Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) which acts as a cyclooxygenase- 2 inhibitor but also has other novel pharmacological features which account for its effect in the control of pain and inflammation. It has become a leading NSAID in over 50 countries worldwide. This book provides a comprehensive and fully up-to-date critical review of the published literature on nimesulide, including comparisons with anti-inflammatory, analgesic and antipyretic agents. The emphasis is on the action of nimesulide in relation to its therapeutic and side effects in comparison with other established NSAIDs, including the new class of Coxibs. The chapters are written by leading experts and cover development of nimesulide, including synthesis and production, introduction, and approved uses and applications, followed by pharmacokinetics and toxicological properties, adverse reactions and their mechanisms.

Nimesulide. --- Pharmacology. --- Drug effects --- Medical pharmacology --- Medical sciences --- Chemicals --- Chemotherapy --- Drugs --- Pharmacy --- Physiological effect --- Analgesics --- Antipyretics --- Cyclooxygenase 2 --- Nonsteroidal anti-inflammatory agents --- Sulfonamides --- Inhibitors --- Toxicology. --- Pain Medicine. --- Rheumatology. --- Immunology. --- Human physiology. --- Anesthesiology. --- Pharmacology/Toxicology. --- Human Physiology. --- Medicine --- Pharmacology --- Poisoning --- Poisons --- Anaesthesiology --- Surgery --- Human biology --- Physiology --- Human body --- Immunobiology --- Life sciences --- Serology --- Internal medicine --- Connective tissues --- Joints --- Toxicology --- Diseases --- Algiatry --- Pain medicine.

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The past decades have seen major developments in the understanding of the cellular and molecular biology of cancer. Significant progress has been achieved regarding long-term survival for the patients of many cancers with the use of tamoxifen for treatment of breast cancer, treatment of chronic myeloid leukaemia with imatinib, and the success of biological drugs. The transition from cytotoxic chemotherapy to targeted cancer drug discovery and development has resulted in an increasing selection of tools available to oncologists. In this Special Issue of Pharmaceuticals, we highlight the opportunities and challenges in the discovery and design of innovative cancer therapies, novel small-molecule cancer drugs and antibody–drug conjugates, with articles covering a variety of anticancer therapies and potential relevant disease states and applications. Significant efforts are being made to develop and improve cancer treatments and to translate basic research findings into clinical use, resulting in improvements in survival rates and quality of life for cancer patients. We demonstrate the possibilities and scope for future research in these areas and also highlight the challenges faced by scientists in the area of anticancer drug development leading to improved targeted treatments and better survival rates for cancer patients.

graphene oxide --- indole --- androgens --- cyclooxygenase-2 --- cyclooxygenase-1 --- heteropolysaccharide --- drug conjugation --- drug delivery --- ellipticine --- chemical linker --- oesophageal cancer --- antiproliferative activity --- topoisomerase II --- ?-lactam --- DSD --- antibody --- topoisomerase inhibitors --- magnetic targeting --- cisplatin resistance --- steroidogenesis --- [18F]FDG PET/CT --- heterocyclic chemistry --- dehydroepiandrosterone --- antimitotic --- 3-vinylazetidin-2-ones --- glioblastoma --- and cancer therapy --- intestinal mucositis --- Combretastatin A-4 --- metabolism --- anti-cancer drugs --- maghemite --- COX-1 inhibitor --- anticancer --- CYP17A1 --- conjugate and hybrid drugs --- inflammation --- snticancer drugs --- P450c17 --- tumorigenesis --- cisplatin --- biomarker profiling --- cancer drug design --- tubulin --- cytochrome P450 --- 5-fluorouracil --- prostate cancer --- abiraterone --- NCI screen --- radiation --- cancer immunotherapy --- microtubule targeted drugs --- cancer --- treatment resistance

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MicroRNAs (miRs) are small noncoding RNAs that function as post-transcriptional regulators of gene expression and have important roles in almost all biological pathways. Deregulated miR expression has been detected in numerous cancers, where miRs act as both oncogene and tumor suppressors. Due to their important roles in tumorigenesis, miRs have been investigated as prognostic and diagnostic biomarkers and as useful targets for therapeutic intervention. From a therapeutic point of view, two modalities can serve to rectify gene networks in cancer cells. For oncomiRs, a rational means is downregulation through antagomirs. Moreover, observations of the pathological reductions in tumor-suppressive miRs have inspired the concept of “miR replacement therapy” to enhance the amount of these miRs, thereby restoring them to normal levels. However, the clinical applicability of miR-based therapies is severely limited by the lack of effective delivery systems. Therefore, to understand the role of this new class of regulators, we need to identify the mRNA targets regulated by individual miRs as well as to develop specific, efficient, and safe delivery systems for therapeutic miRs.

Breast cancer --- Hypoxia inducible factor 1-alpha (HIF-1α) --- MicroRNA (miRNA) --- miR526b --- miR655 --- Oxidative stress --- Migration --- Cyclooxygenase-2 (COX-2) --- Prostaglandin E2 receptor 4 (EP4) --- PI3K/Akt --- adipokines --- endometrial cancer --- estrogens --- hyperinsulinemia --- insulin --- insulin resistance --- insulin signaling --- insulin-like growth factors --- microRNA --- miRNA --- ovarian cancer --- survival --- prognostic factor --- serum LDH --- blood biomarker --- circulating microRNA --- plasma --- immunotherapy --- immune checkpoint inhibitors --- metastatic melanoma --- hepatocellular carcinoma --- metastasis --- exosome --- bioinformatics analysis --- renal cancer --- RCC --- ccRCC --- meta-analysis --- miRNAs --- normal B-cell development --- B-CLL --- miRNA-transcription factor network --- regulation --- biomarker --- therapy --- prognosis --- diagnosis --- progression --- prediction --- smoking --- non-small cell lung cancer --- methylation --- miR-584-5p --- YKT6 --- snoRNA --- 2′-O-methylation --- pseudouridylation --- malignant melanoma --- cancer stem cell --- stemness --- head and neck squamous cell carcinoma --- colon cancer --- cancer stem cells --- microRNAs --- deformability --- PARP --- replication stress --- targeted therapy --- breast cancer --- circulating biomarkers --- medulloblastoma --- brain tumour --- subgroups --- stem cells --- n/a --- 2'-O-methylation