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Modern gene profiling techniques have allowed in recent years considerable progresses in the knowledge of molecular alterations in the context of non-small cell lung cancer (NSCLC). In some cases, these alterations have been recognized as having a pathogenic role and targeted therapies capable of inhibiting tumor proliferation by selective and specific blocking of the enzymatic activity of the related abnormal proteins have been developed. This has made it possible to improve the effectiveness of the treatments by minimizing toxicity. Today it is essential to apply Comprehensive Genomic Profiling methods also in clinical practice, in order to allow the best treatment available for each patient, possibly also in the context of clinical trials. Below we report the clinical history of a patient with advanced stage adenocarcinoma of the lung with molecular diagnosis of RET fusion, treated with pralsetinib with excellent clinical and radiological response and good tolerability. This clinical case emphasizes the importance of the broader molecular profiling in patients with advanced NSCLC (especially for non-squamous histology) from the diagnosis before starting first-line treatment.

Advances in cancer biology research led to the identification of new molecular drivers in non-small cell lung cancer. These alterations should be searched especially in young and never-smoker patients, in order to ensure access to targeted therapies. In particular, RET mutations occur in 1-2% of lung adenocarcinomas and represent the molecular target of innovative treatments such as pralsetinib. The Next Generation Sequencing provides a comprehensive genomic profiling both on tissue and blood sampling. The liquid biopsy could be extremely advantageous, as it is a simple, non-invasive and repeatable test. We report the case of a non-smoker woman with metastatic lung adenocarcinoma unresponsive to chemotherapy and immunotherapy. RET mutation (RET-KIF5B fusion) was found by liquid biopsy. The patient started therapy with pralsetinib obtaining an early radiological response and a significant clinical benefit.

Objectives: Object of this work is to evaluate activity and tolerance of Celecoxib in out-patient's department practice., Patients and Methods: In this study we enlisted 46 patients, affected by pain of inflammatory or degenerative origin; any of them ever did continued therapy with NSAIDs before. We administered 200 mg daily dose of Celecoxib for at least three months. Each patient has been evaluated by the Visual Analogic Score (VAS) Scale before and after the therapy., Results: The data We obtained agree with those of multicenter studies like CLASS. Celecoxib had similar efficacy respect with traditional NSAIDs, with good control of pain in both osteoarthrosic and arthritic pain (p < 0.000). Not good results were obtained for control of acute-onset pain. In our population We didn't find side-effects different from those included in the technical-form of the drug. The only patient who complained of epigastric pain did not stop the treatment, because the symptom resolved with assumption of the drug during meals., Conclusions: By the analysis of the results We consider Celecoxib useful for the control of pain in the treatment of osteoarthrosis and autoimmune diseases like Rheumatoid Arthritis. Anyway, treatment with Celecoxib (as with all Coxib-family drugs) should be reserved for long-lasting treatments in patients at risk for gastrointestinal bleeding.

Progressive increase of the average lifespan pushed up the number of the elderlies in the population. The subsequent spread of degenerative conditions such as osteoarthritis has inflated the request of NSAID despite their frequent toxicity. Side effects of NSAID are sometimes severe and mainly target gastrointestinal tract, renal and platelets function. It has been estimated that around 70% of the patients treated with NSAID develop some degree of gastric damage, ranging from aspecific dyspeptic syndromes to ulcerative diseases. Drugs are now available that selectively inhibit the cyclooxygenase-2: this enzyme is involved in the synthesis of prostaglandins during the inflammatory response. These new drugs have opened new perspectives in the treatment of arthritis; they allow COX-1 to work regularly, so that those prostaglandins that are involved in the maintenance of a regular function of the gastrointestinal tract mucosa and of the platelets. Celecoxib was the firstborn of these new drugs. Differently from FANS, COXIB has got less side effects on gastrointestinal tract and platelets function. Based on the evidence of the more recent clinical experience COXIB has to be recommended; in particular celecoxib, at a schedule of 200-400 mg/die, was shown to be highly effective in the symptomatic treatment of osteoarthritis and rheumatoid arthritis.

Background: We present the case of acute renal failure complicating the course of therapy with both ketorolac (non-selective Non-Steroidal Anti-inflammatory Drug, NSAID), and celecoxib (COX-2 Selective Inhibitor) in an elderly woman with chronic liver disease, heart failure and chronic renal failure. The main effect of NSAIDs is the inhibition of cyclooxygenase (COX), the enzyme involved in prostaglandins synthesis. The nephrotoxicity of NSAIDs is linked to this effect since prostaglandins not only act in response to inflammatory stimuli, but also play a role as modulators of some physiological renal functions. Under conditions of reduced renal perfusion, acute renal failure secondary to NSAIDs use may occur if the vasoconstrictive forces stimulated to maintain the filtrating function are not balanced by prostaglandin-induced vasodilatation. About ten years ago, two COX isoforms were demonstrated: COX-1 whose products are involved in regulating physiological functions and COX-2 which is expressed by a number of inflammatory stimuli. The discovery of molecular differences between COX-1 and COX-2 allowed the development of pharmacological agents selectively inhibiting COX-1 or COX-2. Selective inhibitors of COX-2 are now available. However, COX-1 products are involved in inflammatory reactions, whereas COX-2 products play a physiological role in many tissues and organs, including the kidney. These observations raised many doubts regarding the renal safety of COX-2 Inhibitors before they became commercially available. These doubts have been recently confirmed in the Literature., Conclusions: The case we report seems to confirm that, in patients at risk, the renal adverse effects of non-selective NSAIDs and of COX-2 Inhibitors could be the same due to the similar physiological role of COX-1 and COX-2-dependent prostaglandins.

The Authors summarize the current knowledge on a new class of nonsteroidal anti-inflammatory drugs (NSAIDs), the coxib (celecoxib and rofecoxib), in the treatment of rheumatic diseases. Celecoxib and rofecoxib are selective cyclooxygenase-2 (COX-2) inhibitors which possess the same anti-inflammatory and analgesic activities, but a better gastric tolerability compared to the non-selective COX-1 and COX-2 inhibitors. The Authors also report other possible therapeutic effects of these NSADIs as evidenced by the more recent data of the literature. Celecoxib seems to reduce the incidence of new polyps in patients with familial adenomatous polyposis. It has been suggested the use of celecoxib as a protective drug against the development of colorectal cancer. Other (neoplastic) or pre-neoplastic conditions, such as bladder dysplasia, Barret esophagus, attinic keratosis and Alzheimer's disease seem to have benefit from this class of drugs.

Ethyl esters of [(1-carbethoxymethyl-1H-indazol-3-yl)oxy]-acetic acid; (2-carbethoxy-3,4-dihydro-4-oxo-3-quinazolinacetic acid; [(1H-indazol-3-yl)oxy] acetic acid; o.aminoippuric acid; (2-carbethoxy-4-oxo-1,2,3,4--tetrahydro)-3-quinazolin acetic acid; (3-hydroxy-1H-indazol-1-yl)acetic acid; (1H-indazol-3-on-2-yl)acetic acid have been isolated and identified from a reaction between equivalent quantities of 1H-indazol-3-ol and ethyl chloroacetate in ethanol. The mechanism of their formation and, particularly, the ring enlargement of indazole to tetrahydroquinazoline is discussed. I.R. and N.M.R. spectra of these esters and of the acids obtained from them by alkaline hydrolysis are also described.

Since oximinyliminopyrrazoline ester (OPmp) present a peculiar characteristic in the omogenous peptide synthesis, the use of them, also in the synthesis of bradikinine by the solid phase technique, was duly taken into consideration and tried out. This synthesis was achieved by employing N-protected amino acid OPmp esters containing a methoxycarbonyl or a benzylaminocarbonyl as the acyl function in position 5 of the pyrazoline ring. No significant differences were found in the reactivity of such derivatives in respect of OPmp esters containing the benzyloxycarbonylglycyl moiety. The biological activity of the synthetized braikinine is similar to that of a sample of natural "standard".