Next generation immunotherapy for pancreatic cancer: DNA vaccination is seeking new combo partners

Pancreatic Ductal Adenocarcinoma (PDA) is an almost incurable radio- and chemo-resistant tumor, and its microenvironment is characterized by a strong desmoplastic reaction associated with a significant infiltration of T regulatory lymphocytes and myeloid-derived suppressor cells (Tregs, MDSC). Investigating immunological targets has identified a number of metabolic and cytoskeletal related molecules, which are typically recognized by circulating antibodies. Among these molecules we have investigated alpha-enolase (ENO1), a glycolytic enzyme that also acts a plasminogen receptor. ENO1 is also recognized by T cells in PDA patients, so we developed a DNA vaccine that targets ENO1. This efficiently induces many immunological processes (antibody formation and complement-dependent cytotoxicity (CDC)-mediated tumor killing, infiltration of effector T cells, reduction of infiltration of myeloid and Treg suppressor cells), which significantly increase the survival of genetically engineered mice that spontaneously develop pancreatic cancer. Although promising, the ENO1 DNA vaccine does not completely eradicate the tumor, which, after an initial growth inhibition, returns to proliferate again, especially when Tregs and MDSC ensue in the tumor mass. This led us to develop possible strategies for combinatorial treatments aimed to broaden and sustain the antitumor immune response elicited by DNA vaccination. Based on the data we have obtained in recent years, this review will discuss the biological bases of possible combinatorial treatments (chemotherapy, PI3K inhibitors, tumor-associated macrophages, ENO1 inhibitors) that could be effective in amplifying the response induced by the immune vaccination in PDA

Hypertensive Disorders of Pregnancy and Fetal Growth Restriction: Clinical Characteristics and Placental Lesions and Possible Preventive Nutritional Targets

Background: The purpose of this study was to describe the placental lesions in pregnancies complicated by hypertensive disorders (HDP) and/or fetal growth restriction (FGR) and in uneventful control pregnancies. Methods: This is a case control study that included singleton pregnancies with HDP and normally grown fetus (HDP-AGA fetus), with HDP and FGR, early FGR, late FGR, and uneventful pregnancies. Feto-placental Doppler velocimetry and sFlt-1/PlGF ratio were performed. Placental histology was evaluated blinded according to the Amsterdam Consensus criteria. Results: Placental lesions with maternal vascular malperfusion (MVM) were significantly more frequent in HDP-FGR and early FGR (92% and 83%). MVM were significantly associated with abnormal feto-placental Doppler parameters, especially in early FGR. Delayed villous maturation (DVM) was associated with late FGR (83%). HDP-AGA fetus cases presented a heterogeneous pattern of placental lesions, including 60% of cases with MVM, but were not associated with abnormal Doppler feto-placental velocimetry. Conclusions: We found a prevalence of placental maternal vascular malperfusion in HDP-FGR and early FGR groups. These lesions were also associated with abnormal, anti-, and angiogenic markers. Conversely HDP-AGA fetus and late FGR presented more heterogeneous placental lesions not severe enough to cause feto-placental Doppler anomalies. These conditions are likely associated with different etiologies, such as maternal pre-pregnancy risk factors for metabolic syndrome. These findings suggest a possible preventive nutritional approach in addition to low-dose aspirin in pregnant women with predisposing factors for HDP-AGA fetuses and late FGR

Stretto di Sicilia: Rapporto tecnico sui campionamenti acustici e biologici – Echo-survey “Ancheva 2011”

La campagna oceanografica Ancheva 2011, condotta dal Gruppo di Acustica Applicata alla valutazione delle Risorse dell’IAMC-CNR (U.O.S. di Capo Granitola - Campobello di Mazara) ha avuto come principale obiettivo la valutazione della distribuzione ed abbondanza di piccoli pelagici (prevalentemente sardine e acciughe) nell’area dello Stretto di Sicilia e della Piattaforma Maltese con l’impiego di strumentazione elettroacustica. L’attività di ricerca, svolta nel periodo 20 Giugno – 12 Luglio 2011 a bordo della N/O “Dallaporta”, è parte integrante del progetto MEDIterranean Acoustic Surveys (MEDIAS), finanziato all’interno dell’European Data Collection Regulation. In particolare, la campagna ha permesso di effettuare un Echosurvey nello Stretto di Sicilia (GSA 16 – FAO sub area 37.2.2) il cui scopo principale è quello di eseguire un’investigazione interdisciplinare per stimare abbondanza e distribuzione di organismi pelagici sulla piattaforma meridionale della Sicilia, da Marsala a oltre Capo Passero. Grazie al supporto del programma MEDIAS ed alla collaborazione tra i ricercatori dell’IAMC-CNR ed il Malta Centre for Fisheries Sciences (MCFS), un survey acustico è stato svolto anche nelle acque Maltesi

IN "POLPO ... SITION" E ALTRI BREVI RACCONTI

Assalito dalla felicità corsi al mare, guardai l’acqua e fui preso da una forza, non mia, non umana che mi trascinò in acqua. Lì venni rapito da fantastiche sensazioni, l’adrenalina salì a mille, vidi un enorme creatura che suscitò in me delle emozioni mai provate prima, si era avvicinata talmente tanto che stava per toccarmi e, appena lo fece, il mio corpo si illuminò magicamente, le mie mani iniziarono pian piano ad assottigliarsi, il mio petto diventava sempre più piccolo e tondo e da lì a poco, ero diventato un polpo

Maternal Risk Factors Associated with Antepartum Stillbirth

Background: Stillbirth is a worldwide devastating adverse pregnancy outcome and specific maternal conditions have been associated with an increased risk of fetal death. However, despite the worldwide increased efforts in prevention of stillbirth, little improvements have been achieved in recent years. Our aim was to explore the role of maternal conditions that can be ascertained at the beginning of pregnancy (i.e., demographic and medical conditions/diseases) and estimate their contribution to antepartum stillbirth. An early identification of risk factors could offer to high-risk pregnancies a tailored antenatal surveillance by trained staff leading to a potential reduction of stillbirth rates. Methods: Retrospective case-control study in singleton pregnancies. The difference between fetal survival rates in women with or without risk factors was evaluated. Results: Antepartum stillbirth occurs more frequently in infertile, older women, with systemic diseases. Maternal conditions may affect fetal outcome in a time-dependent manner. Subdividing cases in early stillbirths (before 28 weeks of gestation) and late stillbirth (≥28 weeks of gestation) we observed that early stillbirths are associated with assisted reproductive technologies (Odds Ratio (OR) 3.10; 95% Confidence Interval (CI) 1.43–6.71), maternal age above 35 years (OR 1.59; 95% CI 1.17–2.17) and pre-gestational hypertension (OR 3.68; 95% CI 1.28–10.56). Autoimmune disease (OR 6.55; 95% CI 2.90–14.80), inherited thrombophilia (OR 2.94; 95% CI 1.40–6.18) and pre-gestational diabetes (OR 7.57; 95% CI 2.17–26.35) are independent risk factors for late stillbirths. Further, the risk of stillbirth rises with the increasing of the number of pathological maternal clinical conditions, reaching an OR of 5.27 (95% CI 2.32–11.98) in cases of mother with three or more conditions/diseases. Conclusions: Early awareness of the maternal conditions/diseases addressable at the beginning of pregnancy is crucial to offer a personalized plan for high quality care during gestation; for the prevention of stillbirth, a cared clinical management should acknowledge that pregnancies can be affected more severely and earlier as the number of abnormal maternal conditions increases

Next Generation Immunotherapy for Pancreatic Cancer: DNA Vaccination is Seeking New Combo Partners

Pancreatic Ductal Adenocarcinoma (PDA) is an almost incurable radio- and chemo-resistant tumor, and its microenvironment is characterized by a strong desmoplastic reaction associated with a significant infiltration of T regulatory lymphocytes and myeloid-derived suppressor cells (Tregs, MDSC). Investigating immunological targets has identified a number of metabolic and cytoskeletal related molecules, which are typically recognized by circulating antibodies. Among these molecules we have investigated alpha-enolase (ENO1), a glycolytic enzyme that also acts a plasminogen receptor. ENO1 is also recognized by T cells in PDA patients, so we developed a DNA vaccine that targets ENO1. This efficiently induces many immunological processes (antibody formation and complement-dependent cytotoxicity (CDC)-mediated tumor killing, infiltration of effector T cells, reduction of infiltration of myeloid and Treg suppressor cells), which significantly increase the survival of genetically engineered mice that spontaneously develop pancreatic cancer. Although promising, the ENO1 DNA vaccine does not completely eradicate the tumor, which, after an initial growth inhibition, returns to proliferate again, especially when Tregs and MDSC ensue in the tumor mass. This led us to develop possible strategies for combinatorial treatments aimed to broaden and sustain the antitumor immune response elicited by DNA vaccination. Based on the data we have obtained in recent years, this review will discuss the biological bases of possible combinatorial treatments (chemotherapy, PI3K inhibitors, tumor-associated macrophages, ENO1 inhibitors) that could be effective in amplifying the response induced by the immune vaccination in PDA