Elongation Factor 1 alpha interacts with phospho-Akt in breast cancer cells and regulates their proliferation, survival and motility

BACKGROUND: Akt/PKB is a serine/threonine kinase that has attracted much attention because of its central role in regulating cell proliferation, survival, motility and angiogenesis. Activation of Akt in breast cancer portends aggressive tumour behaviour, resistance to hormone-, chemo-, and radiotherapy-induced apoptosis and it is correlated with decreased overall survival. Recent studies have identified novel tumor-specific substrates of Akt that may provide new diagnostic and prognostic markers and serve as therapeutic targets. This study was undertaken to identify pAkt-interacting proteins and to assess their biological roles in breast cancer cells. RESULTS: We confirmed that one of the pAkt interacting proteins is the Elongation Factor EF1alpha. EF1alpha contains a putative Akt phosphorylation site, but is not phosphorylated by pAkt1 or pAkt2, suggesting that it may function as a modulator of pAkt activity. Indeed, downregulation of EF1alpha expression by siRNAs led to markedly decreased expression of pAkt1 and to less extent of pAkt2 and was associated with reduced proliferation, survival and invasion of HCC1937 cells. Proliferation and survival was further reduced by combining EF1alpha siRNAs with specific pAkt inhibitors whereas EF1alpha downregulation slightly attenuated the decreased invasion induced by Akt inhibitors. CONCLUSION: We show here that EF1alpha is a pAkt-interacting protein which regulates pAkt levels. Since EF1alpha is often overexpressed in breast cancer, the consequences of EF1alpha increased levels for proliferation, survival and invasion will likely depend on the relative concentration of Akt1 and Akt2

UNA PANCREATITE ATIPICA

La diagnosi precoce anche nelle MK atipiche/incomplete è fondamentale, considerando che la prognosi è legata all’inizio tempestivo della terapia, in grado di ridurre il rischio di insorgenza di anomalie coronariche

UNA MANO TROPPO BIANCA

La leucemia neonatale/congenita (esordio entro i 30 giorni di vita) \ue8 rara; meno dell\u20191% dei casi di leucemia infantile sono, infatti, diagnosticati nei neonati, con stime di incidenza di 1-5 casi per milione di nati vivi

Cosa deve sapere il pediatra della linfoistiocitosi emofagocitica attraverso i casi degli specializzandi

Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome caused by severe hypercytokinemia due to a highly stimulated but ineffective immune response. HLH is not a disease by its own but is rather a common final consequence of an inherited or acquired inability of the immune system to cope with a trigger, which in most cases is an infection. HLH in autoinflammatory and autoimmune conditions is usually termed macrophage activation syndrome (MAS) and can be as severe as other forms of HLH. In absence of treatment HLH has a high mortality rate due to the overwhelming immune activation, and early recognition with prompt immunosuppressive treatment may be life saving. The paper presents four cases of HLH/MAS: each one has a different underlying cause and shows a possible presenting picture of the disease, helping paediatrician to recognize it

Una varicella con finale a sorpresa

La fascite necrotiz- zante \ue8 una patologia grave e, se non trattata, rapidamente fatale, caratterizzata da necrosi dei tessuti molli, delle fasce e della cute sovrastante, che pu\uf2 portare a insufficienza multiorgano con shock settico (0,4-0,5 casi su 100.000, mortalit\ue0 del 20-34%)

Oral Administration of Lactobacillus Reuteri Improves Periodontal Disease in Children and Adolescents with Type 1 Diabetes

Objectives: There is disagreement on the effect of diabetes on oral hygiene. Probiotics creating a biofilm could protect the oral tissues against periodontal bacteria. We aimed to assess the effects of Lactobacillus reuteri administration upon the oral health of children and adolescents with type 1 diabetes (T1D). Methods: Forty-three patients (11.3±2.77 yrs.; T1D duration 58.2±38.0 months) were enrolled and randomly assigned to Group A (probiotic - 10^8 CFU/day for 3 months) and Group B (no probiotic). Full Mouth Plaque Score (FMPS), Full Mouth Bleeding Score (FMBS), insulin dose (IU/kg/day), and HbA1c were measured at baseline (T0) and 3-months after (T1). Results: FMPS significantly improved in both Group A and B (p<0.05). In Group B insulin dose increased (p=0.01) and HbA1c improved (p<0.001) at T1; in Group A the metabolic control was unchanged. In Group A, 13 out 22 patients reported a regular probiotic intake (Group A1), while the other ones used it sporadically (Group A2). Despite FMPS and FMBS values were not different between groups at T0, they were significantly lower (p<0.05) in Group A1 respect to Group A2 at T1 and longitudinally decreased in Group A1 but not in Group A2. Conclusions: Our preliminary data suggest that 3-months administration of probiotic might improve the oral health of children and adolescents with T1D and confirm the influence of the glycemic control

The Role of 24-h Ambulatory Blood Pressure Monitoring in Children and Adolescents with Type 1 Diabetes: Early Experience of a Single Centre

Ambulatory blood pressure monitoring (ABPM) permits the observation of blood pressure (BP) in a nonmedical environment. In adults, ABPM is better related to renal damage and cardiovascular morbidity than office BP readings. In early stages of type 1 diabetes (T1DM), the role of ABPM is still controversial

CASO CLINICO: SINDROME DA MICRODELEZIONE 16p11.2 PROSSIMALE

IPOTESI DIAGNOSTICHE E INDAGINI DI I E II LIVELLO Sono stati eseguiti: esami ematici che mostravano TSH ed FT4 normali, cortisolemia ai limiti inferiori con funzionalità surrenalica normale, assetto prepubere ed iniziale resistenza insulinica all’OGTT (glicemia/insulina 4.06, HOMA index 4.10); ecografi a addome (steatosi); fi broscan (fi brosi modesta); cariotipo (femminile normale). DIAGNOSI ED EVENTUALE TERAPIA A completamento diagnostico, veniva eseguita analisi microarray che rilevava una delezione di circa 813kb in 16p11.2 arr[hg19] 16p11.2(29,427,215-30,240,227)x1, comprendente la delezione di 593kb responsabile della sindrome da Microdelezione 16p11.2 Prossimale. Tale sindrome, da geni contigui, è caratterizzata da ritardo dello sviluppo e del linguaggio, deficit cognitivo lieve, disabilità sociale (disturbi dello spettro autistico), lievi dismorfismi variabili, anomalie all‘EEG, predisposizione all’obesità, anomalie vertebrali. La microdelezione 16p11.2 (Gruppo 1) spiega tutte le caratteristiche cliniche presentate dalla nostra paziente. La presenza di obesità, in assenza del coinvolgimento del gene riconosciuto come causativo della stessa, fa presupporre che la delezione in questione interessi una regione genica implicata nella predisposizione all’obesità, non ancora descritta in letteratura

Persistent intestinal bleeding due to severe CMV-related thrombocytopenia in a preterm newborn

The optimal threshold for neonatal platelet transfusions in sick newborns is still uncertain. We report a congenital cytomegalovirus (CMV) infection in a premature neonate with severe thrombocytopenia who subsequently presented with necrotizing enterocolitis and intestinal bleeding. The baby recovered after platelet transfusions were discontinued and the therapy was switched from intravenous ganciclovir to oral valganciclovir. We discuss both measures, speculating on the key role of platelet transfusions

Group B streptococcal infections in the newborn infant and the potential value of maternal vaccination

Group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections in developed countries. Early-onset disease (EOD) occurs at day 0-6 and late-onset disease occurs at day 7-89. Currently, the prevention of EOD relies upon intrapartum antibiotic prophylaxis (IAP) given to women who are GBS positive at prenatal screening or women with risk factors for EOD. Although successfully implemented, IAP has not fully eradicated EOD, and incidence rates of late-onset disease remain unchanged. Furthermore, antibiotic resistance may result from widespread antibiotic use. New prophylactic strategies are therefore of critical importance. A vaccine active against GBS, administered during pregnancy and combined with targeted IAP, could overcome these problems and reduce the mortality and morbidity associated with invasive diseases