• Observations were made with and without inhibition of constitutive (endothelial constitutive NOS (ecNOS) and COX‐1) and inducible isoforms (iNOS and COX‐2) of NOS and COX. (ersjournals.com)
  • Constitutive, but not inducible, isoforms of cyclo-oxygenase and nitric oxide synthase play an important role in abnormal microvessel responses to carbon dioxide and hydrogen ions in hyperoxia-injured lungs. (ersjournals.com)
  • However, these previous studies did not determine the relative contributions of COX (COX‐1 and COX‐2) and nitric oxide synthase (NOS) isoforms (endothelial constitutive (ecNOS) and inducible NOS (iNOS)) to the abnormal acinar microvessel response to HA 4 , 7 . (ersjournals.com)
  • Two isoforms of cyclooxigenase (COX) enzyme are responsible for prostaglandin (PG) synthesis: COX-1 and COX-2. (fxr-agonists.com)
  • There are two isoforms of COX, COX-1 (constitutive) and COX-2 (inducible). (mattek.com)
  • Cyclooxygenase (COX), the key enzyme in prostaglandin cascade, is expressed in two isoforms: the constitutive COX-1 and the inducible COX-2. (unifg.it)
  • The enzyme cyclooxygenase exists in two different isoforms: COX-1 and COX-2. (osmosis.org)
  • At least two COX isoforms have been identified: COX-1 is predominantly constitutive and expressed in different tissues, such as the stomach, intestine, kidneys and platelets. (bvsalud.org)
  • Aceclofenac is a NSAID that inhibits both isoforms of COX enzyme, a key enzyme involved in the inflammatory cascade. (annapurnapharmacy.com)
  • Cyclooxygenase-2 (COX-2) appears to play an important role in skin carcinogenesis caused by solar ultraviolet radiation (UVR): UVR induces COX-2 expression in human skin, COX-2 activity is upregulated in skin cancers and COX inhibitors reduce UVR-induced tumor formation. (mattek.com)
  • COX inhibitors reduced production of PGE2 and 8IP to below baseline levels, indicating a metabolic rather than free radical mechanism of formation. (mattek.com)
  • Etoricoxib and celecoxib belong to the group of specific COX-2 inhibitors. (trc-p.nl)
  • In theory, these drugs should thus have fewer side effects than non-specific COX inhibitors. (trc-p.nl)
  • Some COX-2 inhibitors appear to increase the risk of cardiovascular adverse events in a dose-related fashion and have been withdrawn. (trc-p.nl)
  • Calculating the patient's baseline risk of cardiovascular disease may be wise, and COX-2 inhibitors should not be prescribed to patients with cardiovascular disease or diabetes or those at increased risk of cardiovascular events unless necessary. (trc-p.nl)
  • COX-2 inhibitors should then be used in the lowest effective doses for short periods (weeks) only. (trc-p.nl)
  • If pain control in older patients with a history of gastrointestinal bleedings with paracetamol is insufficient, COX-2 inhibitors can be prescribed. (trc-p.nl)
  • Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C: Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? (lgmpharma.com)
  • Zhang J, Ding EL, Song Y: Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials. (lgmpharma.com)
  • The mechanism of action of Carprofen, like that of other NSAIDs, is believed to be associated with the inhibition of cyclooxygenase activity. (drugs.com)
  • Inhibition of COX-1 is thought to be associated with gastrointestinal and renal toxicity while inhibition of COX-2 provides anti-inflammatory activity. (drugs.com)
  • 3 In an in vitro study using canine cell cultures, Carprofen demonstrated selective inhibition of COX-2 versus COX-1. (drugs.com)
  • The nitric oxide produced by ecNOS attenuated COX‐1 activity in injured arterioles and venules, but carbon dioxide enhanced it, leading to paradoxical dilatation of these microvessels under hypercapnic conditions with ecNOS inhibition. (ersjournals.com)
  • Although a high hydrogen ion concentration was unnecessary for excitation of COX‐1, venule constriction in response to H + was enhanced by COX‐1 inhibition. (ersjournals.com)
  • In another study, it was found that this hypercapnia-associated venule dilatation in intact lungs is significantly attenuated in hyperoxia-injured lungs due to inhibition of COX activity by excessive NO 7 . (ersjournals.com)
  • Despite that COX-2 is typically considered an inducible isoform highly expressed during the inflammatory state, a constitutive expression has been demonstrated in several GI tissues, including the murine proximal colon, where products derived from constitutive COX-2 seem to contribute to the tonic inhibition of the contractile activity of circular smooth muscle layer [6]. (fxr-agonists.com)
  • Effects may result from decreased prostaglandin production and inhibition of the enzyme cyclooxygenase which is responsible for the formation of prostaglandins from arachidonic acid. (equimed.com)
  • Dandekar, DS & Lokeshwar, BL 2004, ' Inhibition of cyclooxygenase (COX)-2 expression by tet-inducible COX-2 antisense cDNA in hormone-refractory prostate cancer significantly slows tumor growth and improves efficacy of chemotherapeutic drugs ', Clinical Cancer Research , vol. 10, no. 23, pp. 8037-8047. (elsevierpure.com)
  • This work also suggests that Rho GTPase and COX-2 inhibition could be explored as a therapy for treating advanced breast tumors. (mdm2-inhibitors.com)
  • Through COX-2 inhibition, aceclofenac downregulates the production of various inflammatory mediators including prostaglandin E2 (PGE2), IL-1β, and TNF from the arachidonic acid (AA) pathway. (annapurnapharmacy.com)
  • This resulted in MS-444-mediated inhibition of COX-2 and other ARE-mRNA expression levels. (oncotarget.com)
  • 5-9 Data also indicate that Carprofen inhibits the production of osteoclast-activating factor (OAF), PGE 1 , and PGE 2 by its inhibitory effects on prostaglandin biosynthesis. (drugs.com)
  • Ibuprofen inhibits both cox-1 and cox-2 enzymes. (thebiologygeek.com)
  • Aceclofenac potently inhibits the cyclo-oxygenase enzyme (COX) that is involved in the synthesis of prostaglandins, which are inflammatory mediators that cause pain, swelling, inflammation, and fever. (annapurnapharmacy.com)
  • The primary metabolite, 4'-hydroxyaceclofenac, also minimally inhibits COX-2 with IC50 value of 36uM [ 2 ]. (annapurnapharmacy.com)
  • Etodolac is what is called a COX-preferential NSAID, which means that it inhibits COX-2 much more strongly than COX-1 and this new plane of safety has enabled dogs to have long-term orally administered pain relief with minimal side effects potential. (vin.com)
  • In addition, it inhibits the activation of the inflammatory mediator NF-κB, inhibits p38 MAPK, ERK1/2 and JNK signaling pathways, and inhibits the expression of the LPS receptor TLR4, suggesting that Ramalin has an excellent anti-inflammatory effect. (justia.com)
  • inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis. (medscape.com)
  • Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which decreases formation of prostaglandin precursors. (medscape.com)
  • COX enzymes metabolize arachadonic acid (AA) to eicosanoid products including prostaglandin E2 (PGE-2) thromboxane A2 and PGI-2, which are thought to contribute to skin carcinogenesis. (mattek.com)
  • It is then changing into prostaglandins and proster cyclins by the enzymes cycloxigenous I and cycloexygenase II cox-1. (thebiologygeek.com)
  • Both enzymes produce prostaglandins but we want to keep our constitutive prostaglandins that help maintain our bodies (these come from COX-1) but not make the inflammatory prostaglandins that come from COX-2. (vin.com)
  • NSAIDs like aspirin inhibit all COX enzymes, good and bad alike. (vin.com)
  • The aim of the present study was to compare microvessel responses to hypercapnic and isocapnic acidosis in hyperoxia-injured lungs and to assess the role of constitutive and inducible forms of nitric oxide synthase (NOS) and cyclo-oxygenase (COX). (ersjournals.com)
  • In a previous study, it was demonstrated that HA induces distinct venule dilatation closely associated with vasodilating prostaglandins generated by cyclo-oxygenase (COX), but not by nitric oxide (NO), in intact rat lung 4 . (ersjournals.com)
  • Aim: Cyclo-oxygenase-2 (COX2) plays a prominent role in carcinogenesis. (iiarjournals.org)
  • What makes this class of NSAID special is its preferential suppression of an enzyme called COX-2 (cyclo-oxygenase 2). (vin.com)
  • Cyclo-oxygenase 1, abbreviated COX-1, is what is called a constitutive enzyme. (vin.com)
  • Many of the biochemicals responsible for the pain and inflammation we want to allieviate are produced by an enzyme called cyclo-oxygenase 2. (vin.com)
  • As a class, cyclooxygenase inhibitory NSAIDs may be associated with gastrointestinal, renal and hepatic toxicity. (petsupplies4less.com)
  • With the development of COX-preferential and COX-selective NSAIDs, we can inhibit COX-2 and leave COX-1 alone. (vin.com)
  • The introduction of COX-2 preferential NSAIDs has reduced stomach and intestinal side effects by 50% in humans and has made FDA approval of certain NSAIDs possible for pets. (vin.com)
  • The coxib class of NSAIDs is COX-selective. (vin.com)
  • The side effects of concern are the same with all NSAIDs regardless of their COX selectivity: stomach ulceration, loss of kidney function, and inappropriate bleeding. (vin.com)
  • In the 1990's, NSAIDs that specifically inhibited COX-2 were introduced in the market to minimize gastrointestinal adverse effects associated with common NSAIDs. (bvsalud.org)
  • The inducible cyclooxygenase, COX-2, generates prostaglandins involved in inflammation. (drugs.com)
  • Inflammatory biochemicals responsible for the pain and inflammation we want to alleviate are produced by COX-2. (vin.com)
  • COX-2 is induced in times of inflammation and mostly produces inflammatory biochemicals. (vin.com)
  • Because ibuprofen decreases inflammation, pain, and fever by inhibiting cyclooxygenase activity and prostaglandin synthesis. (thebiologygeek.com)
  • These data suggest that compounds VA441 and VA428, along with their role in inhibiting COX-2 and inflammation, could have a possible therapeutic (topical and systemic) use against skin proliferative disorders, such as psoriasis. (edu.au)
  • Chronic inflammation induced by infection has been postulated to be an important risk factor for various cancers [ 1 , 2 ]. (hindawi.com)
  • Meloxicam is not a specific COX-2 inhibitor, because it has at low doses also some COX-1 inhibitory effect. (trc-p.nl)
  • The ability of N2IC to enhance tumor progression in SC-M1 cells was suppressed by knockdown of COX-2 or treatment with NS-398, a COX-2 inhibitor. (tmu.edu.tw)
  • DuP 697 is a potent and selective inhibitor of cyclooxygenase-2 (IC 50 values are 10 and 800 nM for COX-2 and COX-1 respectively). (tocris.com)
  • The purpose of this pilot study was to evaluate the effectiveness of two COX-2 selective non-steroidal anti-inflammatory drugs on pain control after open flap debridement. (bvsalud.org)
  • COX-dependent production of 8IP by human skin equivalents is demonstrated for the first time, suggesting a potential role for this mitogenic metabolite in skin carcinogenesis. (mattek.com)
  • Finally, the results indicate that in vitro human skin equivalents are useful models for study of COX regulation by UVR, and related aspects of human skin carcinogenesis. (mattek.com)
  • Upregulation of NOS was assessed by measuring enzyme levels in lung homogenates by Western blot analysis and enhancement of the COX-related pathway was judged from perfusate concentrations of 6‐ketoprostaglandin F 1α . (ersjournals.com)
  • We have identified CREB-mediated activation of Cox-2 as a potential signaling pathway in prostate cancer which can be blocked with a nontoxic, cost-effective dietary supplement like Nexrutine, demonstrating a prospective for development of Nexrutine for prostate cancer management. (nih.gov)
  • The signalling pathway triggered is different for each EP receptor subtype [2]. (fxr-agonists.com)
  • The in vivo trial was designed as a 2 × 2 factorial arrangement to evaluated the effects of arginine supplementation on inflammatory responses, arginine transporters, arginine catabolism and JAK-STAT signalling pathway in broiler chickens challenged with C. perfringens or without C. perfringens . (biomedcentral.com)
  • We had also previously identified a robust expression of cyclooxygenase-2 (COX2) and its downstream product prostaglandin E 2 (PGE 2 ) throughout the airway tissues of patients with RRP compared with controls, mediated by constitutive activation of the EGFR/Rac1 pathway ( 15 ). (biomedcentral.com)
  • Nexrutine also reduced the expression and promoter activity of Cox-2 in PC-3 cells that express high constitutive levels of Cox-2. (nih.gov)
  • Besides its physiological role, elevated production of PGE2 induced by an up-regulated expression of COX-2 might participate in the impaired motility associated to pathophysiological processes such as inflammatory bowel disease, slow transit constipation or obstructive bowel disorders [2,7-9]. (fxr-agonists.com)
  • UVR enhanced COX-2 expression without effecting COX-1, and increased production of both PGE2 and 8IP. (mattek.com)
  • Additional experiments were conducted to study regulation of COX expression by cytokines in the absence of UVR. (mattek.com)
  • IL-1α, IL-1β or TNFα induced expression of COX-2 without effect on COX-1, and in-creased production of PGE-2 and 8IP. (mattek.com)
  • Constitutive expression of Notch2 intracellular domain (N2IC), the activated form of Notch2 receptor, promoted both cell proliferation and xenografted tumor growth of human stomach adenocarcinoma SC-M1 cells. (tmu.edu.tw)
  • Furthermore, N2IC bound to COX-2 promoter and induced COX-2 expression through a CBF1-dependent manner in SC-M1 cells. (tmu.edu.tw)
  • The significance of COX-2 in prostate cancer growth and response to chemotherapy was investigated in an androgen-refractory prostate cancer cell line using a Tet-inducible antisense COX-2 expression system. (elsevierpure.com)
  • Conclusions: These results provide direct evidence that constitutive expression of COX-2 in prostate cancer has both angiogenic and cytoprotective functions. (elsevierpure.com)
  • Hyper-expression of COX-2 has been implicated in the pathogenesis of colon-rectal cancer in humans but it appears to play a significant role as a tumour progression factor also in other forms of human cancer, including oral cancer. (unifg.it)
  • The aim of this study was to analyze the expression of COX-2, at the protein level, in 45 cases of oral squamous cell carcinoma. (unifg.it)
  • COX-2 expression appeared particularly abundant in the superficial ulcerated layers of relatively well differentiated carcinomas. (unifg.it)
  • However, we were unable to assess any statistically significant association between COX-2 hyper-expression and tumor site, tumor grading, tumor size, presence of lymph node metastases, tumor stage and age at onset, respectively. (unifg.it)
  • Interestingly, COX-2 expression was detected not only in areas of epithelial dysplasia adjacent to the primary layers (86% of the cases) but also in normal-appearing epithelium at the boundaries of squamous cell carcinoma (77%), indicating a possible involvement in tumour progression by the apparently normal tissue surrounding the lesion. (unifg.it)
  • However, further studies are necessary to understand the exact magnitude of this over-expression and, mostly, the possible role of COX-2 in the pathogenesis and progression of oral cancer. (unifg.it)
  • Arbabi S, Rosengart MR, Garcia I, Jelacic S, Maier RV (2001) Epithelial cyclooxygenase-2 expression: a model for pathogenesis of colon cancer. (springer.com)
  • Thus, the change in expression of these three plasma T H 2-like chemokines may, with future studies, prove to serve as a useful biomarker for predicting disease prognosis. (biomedcentral.com)
  • PGE 2 can bias the adaptive immune response away from an effective T H 1-like pattern ( 16 ), and can enhance expression of T H 2-like chemokines by innate immunocytes ( 16 , 17 ). (biomedcentral.com)
  • In vivo treatment of MS-444 inhibited HuR cytoplasmic localization and decreased COX-2 expression in tumors. (oncotarget.com)
  • Specific COX-2 inhibitory drugs inhibit the inflammatory-induced prostaglandin synthesis, without hindering the constitutive prostaglandin synthesis. (trc-p.nl)
  • Arachidonic acid is a substrate for an enzyme called cyclooxygenase or COX. (osmosis.org)
  • The specificity of a particular NSAID for COX-2 versus COX-1 may vary from species to species. (drugs.com)
  • 2 The constitutive cyclooxygenase, COX-1, synthesizes prostaglandins necessary for normal gastrointestinal and renal function. (drugs.com)
  • It is a constitutive enzyme which means it is always active by contrast cox-2 is an inducible enzyme. (thebiologygeek.com)
  • COX-1 is a constitutive enzyme, meaning that it's always active, while on the other hand, COX-2 is an inducible enzyme, meaning that it must be turned on to function. (osmosis.org)
  • COX-1 enzyme is a constitutive enzyme involved in prostacyclin production and protective functions of gastric mucosa whereas COX-2 is an inducible enzyme involved in the production of inflammatory mediators in response to inflammatory stimuli. (annapurnapharmacy.com)
  • COX-2 responds to tissue trauma and produces prostaglandins involved in the inflammatory response and pain mediation 5 . (bvsalud.org)
  • Neurotensin receptor type 2 is a protein that in humans is encoded by the NTSR2 gene. (wikipedia.org)
  • Regulation of Cox-2 by cyclic AMP response element binding protein in prostate cancer: potential role for nexrutine. (nih.gov)
  • In this report, we use RT-PCR, Western blotting and ELISA to study the effect of UVR on COX message, protein and metabolites, respectively, in the EpiDerm in vitro human skin equivalent. (mattek.com)
  • EpiDerm tissues expressed COX-1 message and protein constitutively, and secreted PGE-2 and 8IP into the culture medium. (mattek.com)
  • COX-2 message and protein were also detectable. (mattek.com)
  • Neuronal nuclei (NeuN) and microtubule-associated protein 2 (MAP2) were detected by Immunofluorescence (IF). (bvsalud.org)
  • Suppression of COX-2 increased Bax protein and decreased Bcl-x L protein in vitro. (elsevierpure.com)
  • ATP2A2, located on 12q23-24.1, encodes the sarcoplasmic/endoplasmic reticulum Ca 2+ -ATP isoform 2 protein (SERCA2), which is a calcium pump. (medscape.com)
  • Concurrently, constitutive AKT phosphorylation in myoma cells was inhibited by resveratrol. (tmu.edu.tw)
  • We found that SC-43 and SC-78 but not regorafenib inhibited constitutive and IL-6-induced STAT3 phosphorylation in HCT-116 and HT-29 cells, respectively. (zhihuiya.com)
  • In this study, we have characterized the T H 2-like chemokine profile (CCL17, CCL18, CCL20, CCL22) in patients with RRP and asked whether it was modulated in patients who had achieved significant clinical improvement. (biomedcentral.com)
  • Expressions of proapoptotic genes, such as cyclooxygenase (COX)-2, p21 and CDKN2, were induced by resveratrol in myoma cells. (tmu.edu.tw)
  • Observed during CRC tumorigenesis is loss of post-transcriptional regulation of tumor-promoting genes such as COX-2, TNFα and VEGF. (oncotarget.com)
  • Moreover, the suppression of tumor progression by Notch2 knockdown in SC-M1 cells was reversed by exogenous COX-2 or its major enzymatic product PGE 2 . (tmu.edu.tw)
  • On the molecular level RhoGDI knockdown led to constitutive activation of multiple Rho GTPases (e.g. (mdm2-inhibitors.com)
  • Thus, EpiDerm tissues behave similarly to in vivo human skin with respect to regulation of COX-2 by solar UVR and cytokines. (mattek.com)
  • The main mechanism of non-steroidal anti-inflammatory drugs is to inhibit either cox-1 or cox-2 or both and reduce the synthesis of prostaglandins and proster cyclins. (thebiologygeek.com)
  • RhoA Rac1 and Cdc42) AS-252424 and in addition resulted in a concomitant upregulation of COX-2 appearance and activity. (mdm2-inhibitors.com)
  • ecNOS and COX‐1, but not iNOS and COX‐2, were upregulated in hyperoxia-injured lungs. (ersjournals.com)
  • One of the goals of pain relief is to inhibit COX-2 without inhibiting its counterpart COX-1. (vin.com)
  • Results: Conditional suppression of COX-2 in PC-3ML caused reduced cell proliferation, decreased levels of phosphorylated AKT, G 0 -G 1 arrest, and increased apoptosis and caspase-3 activity. (elsevierpure.com)
  • These data claim that downregulation of RhoGDI is actually a important mechanism of breasts tumor development which might involve the hyperactivation of Rho GTPases and upregulation of COX-2 activity. (mdm2-inhibitors.com)
  • As upregulated COX-2 activity is certainly broadly implicated in tumor cell development and invasion [7-11] our data offers a feasible hyperlink between downregulation of RhoGDI and following activation of COX-2 to advertise breast malignancy. (mdm2-inhibitors.com)
  • Suppression of tumor cell COX-2 is sufficient to enhance chemotherapy response in prostate cancer. (elsevierpure.com)
  • Previous study showed that the activated Notch1 receptor promoted gastric cancer progression through cyclooxygenase-2 (COX-2). (tmu.edu.tw)
  • Taken together, this study is the first to demonstrate that the Notch2-COX-2 signaling axis plays an important role in controlling gastric cancer progression. (tmu.edu.tw)
  • COX-2 antisense-expressing PC-3ML tumors showed a 57% growth delay compared with nontransfected or vector controls. (elsevierpure.com)
  • Compared with the control group, the occurrence of apoptosis in antisense COX-2 tumors was eight times higher, and the tumor microvessel density was three times lower. (elsevierpure.com)
  • Cyclooxygenase (Cox-2), a pro-inflammatory mediator, is a CREB target that induces prostaglandin E(2) (PGE(2)) and suppresses apoptosis. (nih.gov)
  • Jointly this shows that RhoGDI (RhoGDI-1) and D4-GDI (RhoGDI-2) can possess opposing jobs in the legislation of breast cancers progression. (mdm2-inhibitors.com)
  • 2000. A metabolite of methoxychlor, 2,2-bis( p hydroxyphenyl)-1,1,1-trichloroethane, reduces testosterone biosynthesis in rat leydig cells through suppression of steady-state messenger ribonucleic acid levels of the cholesterol side-chain cleavage enzyme. (cdc.gov)
  • Treatment of LNCaP cells with Nexrutine reduced tumor necrosis factor alpha-induced enzymatic as well as promoter activities of Cox-2. (nih.gov)
  • Deletion analysis coupled with mutational analysis of the Cox-2 promoter identified CRE as being sufficient for mediating Nexrutine response. (nih.gov)
  • We found that the CHH methylation at the promoter and transcript level of OsGSTZ4 were compromised in the osdrm2 (loss of function for CHH methylation) and osrdr2i (defective in RNA-dependent RNA polymerase 2) but did not change in other types of methyltransferases such as osmet1, ossdg714 or osros1. (bvsalud.org)
  • Experimental Design: An antisense COX-2 cDNA construct under the control of a doxycycline-inducible promoter was transfected into a prostate cancer cell line, PC-3ML. (elsevierpure.com)
  • COX may also metabolize AA to 8-isoprostane (8IP), a novel mitogenic prostaglandin previously thought to be formed only via free radical pathways. (mattek.com)
  • They act by inhibiting the enzyme cyclooxygenase (COX), which promotes the release of prostaglandins, prostacyclins and thromboxanes, and activates phagocytes, which, in turn, promote the release of proinflammatory cytokines in response to tissue trauma. (bvsalud.org)
  • Host recognition of microbes happens through pattern reputation receptors, including Toll-like receptors (TLRs)2 that are indicated on many cells, including macrophages, monocytes (1), and keratinocytes (2). (cancer-ecosystem.com)
  • For the control of postoperative pain, administer approximately 2 hours before the procedure. (petsupplies4less.com)
  • and it works by reversibly inhibiting COX in the central nervous system, thereby decreasing production of the prostaglandins that cause fever and pain. (osmosis.org)
  • Most patients (77%) experience pain after scaling and root planing and the mean duration of moderate to intense pain is 6.1 hours 1-2 . (bvsalud.org)
  • COX-2 positivity was associated with CD34 and VEGF positivity, indicating that these vessels were probably neo-formed ones. (unifg.it)
  • Prostaglandin E2 (PGE2) is widely produced in different organs from different species, with relevance in several gastrointesti- nal (GI) functions [1] including mucosal protection, secretion and motility [2]. (fxr-agonists.com)
  • From this study as well as from other works, it appears that indeed COX-2 is over-expressed in this important human malignancy. (unifg.it)