Cooperation between Prostaglandin E2 and Epidermal Growth Factor Receptor in Cancer Progression: A Dual Target for Cancer Therapy

It is recognized that prostaglandin E2 (PGE2) is one key lipid mediator involved in chronic inflammation, and it is directly implicated in tumor development by regulating cancer cell growth and migration, apoptosis, epithelial–mesenchymal transition, angiogenesis, and immune escape. In addition, the expression of the enzymes involved in PGE2 synthesis, cyclooxygenase 2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES1), positively correlates with tumor progression and aggressiveness, clearly indicating the crucial role of the entire pathway in cancer. Moreover, several lines of evidence suggest that the COX2/mPGES1/PGE2 inflammatory axis is involved in the modulation of epidermal growth factor receptor (EGFR) signaling to reinforce the oncogenic drive of EGFR activation. Similarly, EGFR activation promotes the induction of COX2/mPGES1 expression and PGE2 production. In this review, we describe the interplay between COX2/mPGES1/PGE2 and EGFR in cancer, and new therapeutic strategies that target this signaling pathway, to outline the importance of the modulation of the inflammatory process in cancer fighting. © 2023 by the authors

Rhegmatogenous retinal detachment following Nd-YAG laser capsulotomy

Gli AA. riportano uno studio retrospettivo di 487 pazienti sottoposti a capsulotomia Nd-YAG laser effettuata dal gennaio 1985 al dicembre 1988. Otto pazienti hanno sviluppato un distacco retinico regmatogeno posi-trattamento. Sette pazienti erano afachici, uno pseudofachico. L'energia laser utilizzata per la capsulotomia non è stata particolarmente elevata. Le aperture capsulari erano inferiori a 3 mm ., eccetto un caso. L'intervallo tra la capsulotomia e la comparsa del distacco retinico variava dai 2 ai 48 mesi (media 23)

Comportamental model of celecoxib in rat eye

Elevated levels of vascular endothelial growth factor (VEGF) are implicate in progression of diabetic retinopathy. Celecoxib, a COX-2 inhibitor, reduces retinal VEGF expression in a diabetic rat model. The primary goal of this study was to determine in rat the celecoxib disposition in various ocular compartments after intraperitoneal administration. Albino Wistar rats (200 g weight) were used and treated with 3 mg drug. Celecoxib was suspended in 0.5% w/v of carboxy methyl cellulose sodium salt and administered (3mg/rat) to unanaesthetized rat. The animals after pentobarbital (250 mg/kg) were sacrificed at 0.5, 1,2,3,4,8 and 12 hours after celecoxib administration. The plasma was collected and the eyes enucleated immediately and frozen at –80°C. Cornea, lens retina, vitreous and sclera were isolated and drug levels in ocular tissue and plasma were estimated using HPLC method and the concentration-time profiles analysed by compartmental analysis. The plasma and tissue pharmacokinetics parameters of celecoxib were reported

Medication Related Osteonecrosis of the Jaw: Melatonin functions and effects

Bisphosphonates (BPs) are drugs frequently prescribed in therapy of various pathological conditions affecting bones but they may have adverse effects, the most important one is represented by osteonecrosis of the jaws (Bisphosphonates related osteonecrosis of jaws, BRONJ) detected and described by Marx, since 2003, as a painful and nonhealing bone exposure. Despite many researches its exact aetiology, pathogenesis and adequate treatment protocol remain controversial. In the last decade other drugs have been related to this serious disease, now grouped into two categories: BPs and non-BPs (considering other antiresorptive or antiangiogenic medications); and now we describe this pathological condition with acronimus MRONJ (Medication Related Osteonecrosis of the Jaw). According to American Association of Oral and Maxillofacial Surgeons (AAOMS), MRONJ presents with exposed necrotic bone in maxillofacial region for more than 8 weeks, in patients without history of radiation therapy to the orofacial region, which are currently taking (or were) antiresorptive or antiangiogenic agents. MRONJ usually is induced by local trauma, such as tooth extraction or other invasive dental procedures; the risk of developing MRONJ increases proportionally to the dosage and duration of medication intake and it is greater in combination with chemotherapy. Since osteonecrosis seems related mostly to antiangiogenic effect of these drugs we want to evaluate the outcome of pharmacological doses of Melatonin in patient with MRONJ. Melatonin has an important role in angiogenesis increasing VEGF expression. Besides Melatonin has an important anti-inflammatory effect acting as an antioxidant by directly neutralising ROS. More over Melatonin interferes with bone resorption process by down regulation of the Receptor Activator of Nuclear Factor k-B Ligand ((RANKL)-mediated Osteoclast formation and Activation; in addition Melatonin promotes Osteoblast differentiation and stimulates the formation of collagen type I and new mineralised matrix

Possono i bifosfonati causare disturbi oculari?

I bifosfonati sono farmaci principalmente impiegati per prevenire o trattare l’osteoporosi, il morbo di Paget, l’ipercalcemia da tumore e per le condizioni associate ad aumentata attività osteoclastica. Si tratta di una classe di molecole che inibiscono il riassorbimento osseo e nella pratica clinica il loro uso varia in base alle caratteristiche dei singoli prodotti. Segnalazioni spontanee internazionali provenienti dai sistemi di farmacovigilanza riportano dati riguardanti le reazioni avverse a carico dell’apparato visivo associate ai bifosfonati e suggeriscono che questa classe di farmaci può causare gravi effetti avversi oculari, anche se con una bassa incidenza. Scopo del lavoro è stato quello di effettuare una revisione della letteratura sui bifosfonati e gli effetti collaterali a carico dell’occhio, per meglio comprendere questo problema e al fine di informare gli operatori sanitari che devono essere consapevoli di tale possibilità anche se questi effetti oculari possono essere rari. La maggior parte delle segnalazioni riguardano l’acido pamidronico e alendronico. Le linee guida per la cura dei pazienti che assumono bifosfonati suggeriscono in particolare di indirizzare ad un oftalmologo i pazienti che presentino infiammazioni oculari: congiuntiviti aspecifiche raramente richiedono un intervento e diminuiscono progressivamente in intensità mantenendo la terapia con bifosfonati. L’interruzione della terapia può rendersi necessaria nel caso di comparsa contemporanea di più di un effetto collaterale oculare ed è indispensabile in caso di comparsa di scleriti. Sebbene questi effetti oculari possano essere rari con i bifosfonati, gli operatori sanitari devono essere consapevoli di tale possibilità. Pertanto il medico nella gestione di pazienti in terapia con bifosfonati deve effettuare le rispettive raccomandazioni alfine di informarlo sui possibili effetti collaterali ed intervenire opportunamente