169,761 research outputs found
Playing the Devil’s Advocate: Should We Give a Second Chance to mTOR Inhibition in Renal Clear Cell Carcinoma? – ie Strategies to Revert Resistance to mTOR Inhibitors
No full textGaetano Pezzicoli,1,2 Elisabetta Filoni,1,2 Angela Gernone,2 Laura Cosmai,3 Mimma Rizzo,4 Camillo Porta2,5 1Department of Biomedical Sciences and Human Oncology, Post-Graduate School of Specialization in Medical Oncology, University of Bari ‘A. Moro’, Bari, Italy; 2Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy; 3Onconephrology Outpatient Clinic, Division of Nephrology and Dialysis, A.S.S.T. Fatebenefratelli-Sacco, Fatebenefratelli Hospital, Milan, Italy; 4Division of Translational Oncology, I.R.C.C.S. Istituti Clinici Scientifici Maugeri, Pavia, Italy; 5Chair of Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari ‘A. Moro’, Bari, ItalyCorrespondence: Camillo PortaDivision of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Piazza Giulio Cesare, 11, Bari, 70124, ItalyTel +39-080-5594167Fax +39-080-5593477Email [email protected]; [email protected]: In the last decade, the inhibition of the mechanistic target of Rapamycin (mTOR) in renal clear cell carcinoma (RCC) has disappointed the clinician’s expectations. Many clinical trials highlighted the low efficacy and unmanageable safety profile of first-generation mTOR inhibitors (Rapalogs), thus limiting their use in the clinical practice only to those patients who already failed several therapy lines. In this review, we analyze the major resistance mechanisms that undermine the efficacy of this class of drugs. Moreover, we describe some of the possible strategies to overcome the mechanisms of resistance and their clinical experimentation, with particular focus on novel mTOR inhibitors and the combinations of mTOR inhibitors and other anti-cancer drugs.Keywords: everolimus, temsirolimus, Rapa-Link, anti-angiogenics, autophag
Il caso “Champanillo” e l’evocazione di una DOP vitivinicola nella giurisprudenza della Corte di giustizia dell’Unione
No full textLa Corte di giustizia dell’Unione europea, nella sentenza Champanillo (C‐783/19), ha chiarito che la protezione delle DOP prevista dall’art. 103, par. 2, lett. b), del Reg. (UE) n. 1308/2013 si estende anche ai servizi, non richiede identità o similarità tra i prodotti e si fonda sulla percezione del consumatore medio
Il caso «Lactalis» e l’indicazione obbligatoria in etichetta dell’origine dei prodotti agroalimentari
No full textLa Corte di giustizia dell’Unione europea, con la sentenza Lactalis (C-485/18), ha chiarito i limiti entro cui gli Stati membri possono imporre l’indicazione obbligatoria dell’origine del latte e del latte usato come ingrediente, in deroga all’armonizzazione prevista dal regolamento (UE) n. 1169/2011. La Corte ha precisato che tali misure nazionali sono ammissibili ai sensi dell’art. 39, purché fondate su un nesso oggettivo tra origine e qualità dell’alimento e rispondano a finalità di tutela del consumatore. È esclusa la rilevanza di criteri meramente soggettivi o tecnici, come la resistenza al trasporto. La pronuncia contribuisce a definire l’ambito di legittimità della normativa nazionale “di supplenza” in materia di etichettatura d’origine
"Clinical and neuropathological findings of Equine Motor Neuron Disease in two italian horses"
No full textTwo Italian saddle horses, a 10 year old gelding and a 14 year old mare, were admitted with a complain of progressive weight loss and weakness, resulting in excessive lying down on the floor of their box. Appetite was good and micturition and defecation normal. The general physical examination was normal.
The horses underwent a complete neurological examination, cell blood count (CBC), and biochemical profile. Vitamin E plasma levels were not measured because of previous supplementation. Muscle and nerve biopsies were taken from the left sacrocaudalis dorsalis medialis muscle and the ventral branch of the left spinal accessory nerve, respectively. Immediately after euthanasia for humane reasons, cerebrospinal fluid (CSF) was collected and examined and both horses had a neuropathologic examination of the brain and spinal cord. Samples of the left radial and peroneal nerves were also examined in one horse and an electromyographic (EMG) examination was performed under general anaesthesia on the second horse.
Abnormal neurological examination findings were severe generalised muscle atrophy with marked muscle tremors of the antigravitational muscles when the horses were forced to stand, and frequent shifting of the weight from limb to limb. One horse had an abnormal low carriage of the head. Gait was characterised by moderate tetraparesis with hypometria of the four limbs and exercise intolerance. There was no evidence of ataxia. BC, biochemical profile and CSF examination were normal. The EMG showed fibrillation potential in the paravertebral muscles.
Pathological findings were similar in both cases: scattered neuronal degeneration and loss in the ventral horns of the spinal cord and in the caudal brain stem. Affected neurons were swollen and chromatolytic, and occasionally showed intracytoplasmic eosinophilic inclusions. Some degenerating motor neurons were shrunken, sometimes with fragmenting nucleus. Small microglial nodules were also observed at the sites of neuronal loss. PAS-positive and Luxol fast blue-positive ceroidal lipopigment granules were observed in the cytoplasm of many degenerating neurons and some endothelial cells in the affected areas. Occasional perivascular accumulation of macrophages laden with residual ceroidal pigment was also noticed. Examination of spinal accessory, peroneal and radial nerves showed loss of large diameter fibres and axonal degeneration characterised by axonal swelling, myelin ovoids formation and phagocytosis by macrophages. Scattered angular myofibres and occasional hypertrophic fibres were observed in the sacrocaudalis dorsalis medialis muscle
Efficacy of domperidone plus renal diet in slowing the progression of chronic kidney disease in dogs with leishmaniosis
No full textBackground: Chronic kidney disease (CKD) represents the main cause of mortality in dogs with leishmaniosis. Domperidone has recently been reported to improve kidney function in leishmaniotic dogs affected by CKD. Serum symmetric dimethylarginine (sSDMA) has also been shown to be a useful biomarker for earlier detection of decreased kidney function when compared to serum creatinine (sCr). This study aimed to assess the efficacy of domperidone plus renal diet in slowing the progression of nephropathy in leishmaniotic dogs with CKD, evaluating sSDMA and sCr as markers of kidney function. Methods: This study was a therapeutic, prospective, randomized, controlled, 11-month-long field trial. Dogs were recruited if classified as “exposed” to or “infected” with Leishmania infantum and affected by CKD at early stages. After enrolment (T0), dogs were randomized into groups T (treatment) and C (control). All dogs were fed a renal diet and then followed up at 90 (T1), 210 (T2), and 330 (T3) days after inclusion in the study. At T1 and T2, dogs in group T received an oral suspension of domperidone (1 ml/10 kg once a day for up to 28 days). Results: Twenty-two dogs (i.e., n = 12 in group T and n = 10 in group C) completed the study. At T0, the entire population of enrolled dogs presented a mean sSDMA value of 16.5 ± 3.4 μg/dl. At T1 (i.e., after 3 months of renal diet), sSDMA was significantly decreased in both groups, with an sSDMA of 13.1 ± 4.4 μg/dl for the entire population involved. From T1 to T3, sSDMA gradually increased in group C, while remaining stable in group T, which continued to show a significantly lower value of sSDMA at T3 than at T0. Regarding sCr, at T0 and T1, the mean values of the entire population of dogs were 1.1 ± 0.3 and 1.0 ± 0.4 mg/dl, respectively, with no statistical differences between groups T and C. In group T, sCr decreased significantly from T0 to T1, while returning at T3 to values similar to T0. Conclusions: In this study, domperidone plus renal diet reduced the progression of kidney disease in leishmaniotic dogs affected by CKD. Graphical Abstract: [Figure not available: see fulltext.]
Impiego preferenziale del promotore P1 dell’oncogene c-myc in corso di Mieloma Multiplo (MM)
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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