IGF-1 is one of the key molecules in cancer biology; however, little is known about the role of the preferential expression of the premature IGF-1 isoforms in prostate cancer. We have examined the role of the cleaved COO-terminal peptide (PEc) of the third IGF-1 isoform, IGF-1Ec, in prostate cancer. Our evidence suggests that endogenously produced PEc induces cellular proliferation in the human prostate cancer cells (PC-3) in vitro and in vivo, by activating the ERK1/2 pathway in an autocrine/paracrine manner. PEc overexpressing cells and tumors presented evidence of epithelial to mesenchymal transition, whereas the orthotopic injection of PEc-overexpressing, normal prostate epithelium cells (HPrEC) in SCID mice was associated with increased metastatic rate. In humans, the IGF-1Ec expression was detected in prostate cancer biopsies, where its expression correlates with tumor stage. Our data describes the action of PEc in prostate cancer biology and defines its potential role in tumor growth, progression and metastasis.

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BackgroundEc peptide (PEc), resulting from the proteolytic cleavage of the IGF-1Ec isoform, is involved in prostate cancer progression and metastasis, whereas in muscle tissue, it is associated with the mobilization of satellite cells prior to repair. Our aim is to determine the physiological conditions associated to the IGF-1Ec upregulation and PEc secretion in prostate tumors, as well as, the effect of tumor PEc on tumor repair.MethodsIGF-1 (mature and isoforms) expression was examined by qRT-PCR, both in prostate cancer cells co-incubated with cells of the immune response (IR) and in tumors. PEc secretion was determined by Multiple Reaction Monitoring.The effect of PEc, on mesenchymal stem cell (MSC) mobilization and repair, was examined using migration and invasion assays, FISH and immunohistochemistry (IHC). The JAK/STAT signaling pathway leading to the IGF1-Ec expression was examined by western blot analysis. Determination of the expression and localization of IL-6 and IGF-1Ec in prostate tumors was examined by qRT-PCR and by IHC.ResultsWe documented that IL-6 secreted by IR cells activates the JAK2 and STAT3 pathway through IL-6 receptor in cancer cells, leading to the IGF-1Ec upregulation and PEc secretion, as well as to the IL-6 expression and secretion. The resulting PEc, apart from its oncogenic role, also mobilizes MSCs towards the tumor, thus promoting tumor repair.ConclusionsIL-6 leads to the PEc secretion from prostate cancer cells. Apart from its oncogenic role, PEc is also involved in the mobilization of MSCs resulting in tumor repair.Electronic supplementary materialThe online version of this article (10.1186/s10020-018-0003-z) contains supplementary material, which is available to authorized users.

Sixteen patients who had manifested ST segment depression during episodes of paroxysmal supraventricular tachycardia (PSVT) were studied with exercise testing in order to detect coronary artery disease and myocardial ischaemia. No ST segment depression was observed during exercise testing in 15 out of the 16 patients tested. Paroxysms of supraventricular tachycardia associated with ST segment depression occurred during exercise testing in three cases. The ST segment depression was immediately apparent, remained constant throughout the supraventricular tachycardia and was almost instantly abolished following conversion to sinus rhythm. Patients with heart rates greater than 250 beats min-1 during PSVT had marked ST segment depression associated with the tachycardia. These results suggest that coronary artery disease and myocardial ischaemia are not involved in the genesis of ST segment depression during PSVT. Tachycardia per se may be the cause of ST segment depression by altering the slope of phase 2 of the ventricular action potential. Retrograde atrial activation may also induce ST segment shifts in some of the cases.

Σκοπός και Μεθοδολογία της διδακτορικής διατριβής: Η παρούσα διατριβή αποσκοπεί εις την συνολικήν θεώρησιν, την διεξοδικήν μελέτην και την θεολογικήν ερμηνείαν του Μυστικού Δείπνου του Ιησού Χριστού και του Μυστηρίου της Θείας Ευχαριστίας, ως αυτή εκτίθεται εις την διδασκαλίαν των Συνοπτικών Ευαγγελίων, του κατά Ιωάννην, του βιβλίου των Πράξεων Αποστόλων, της Α' προς Κορινθίους Επιστολής, καθώς και της προεκτάσεως του Μυστηρίου εις την ζωήν και την ιστορίαν της Εκκλησίας. Αι βασικαί λοιπόν κατευθύνσεις της ερευνητικής αυτής προσπάθειας θα εστιασθούν εις τους κάτωθι τομείς: 1) Εις τον τονισμόν του ιστορικού χαρακτήρος των σχετικών προς το υπό έρευναν θέμα αγιογραφικών μαρτυριών. 2) Εις την κατανόησιν του εκκλησιολογικού χαρακτήρος των διηγήσεων περί τον Μυστικόν Δείπνον. 3) Αναγκαία διά την παρούσαν εργασίαν είναι και η έμφασις επί της οργανικής ενότητος των διηγήσεων αυτών. Β) Διάρθρωσις της διδακτoρικής διατοιβής 1) Εν τω πρώτω κεφαλαίω, θα προβώμεν εις την ιστορικήν, φιλολογικήν, αλλά και θεολογικήν ανάλυσιν των διηγήσεων περί του Μυστικού Δείπνου του Ιησού Χριστού. Επίσης θα αναλύσωμεν το πρόβλημα του χρόνου τελέσεως αλλά και του χαρακτήρος του Μυστικού Δείπνου. Επόμενον στάδιον θα αποτελέση η παράλληλος εξέτασις του Μυστικού Δείπνου και των εν τω Ιουδαϊσμώ περί την τράπεζαν συνάξεων των θρησκευτικών ομάδων. Θα προβώμεν επίσης και εις την παράλληλον και ενδελεχή ανάλυσιν του Δείπνου μετά των εν τω Ιουδαϊσμώ και τω Ελληνορρωμαϊκώ κόσμω αποχαιρετιστήριων δείπνων. 2) Εν τω δευτέρω κεφαλαίω, θα εξετάσωμεν τας μετά την Ανάστασιν του Κυρίου σχετικάς μαρτυρίας, εις το κατά Λουκάν Ευαγγέλιον και εις το βιβλίον των Πράξεων Αποστόλων. 3) Εν τω τρίτω κεφαλαίω θα ερευνήσωμεν την προέκτασιν του Μυστηρίου της Θείας Ευχαριστίας εις ζωήν της Εκκλησίας κατά την μεταποστολικήν εποχήν. 4) Τέλος, η παρούσα διατριβή θα ολοκληρωθή διά της εκθέσεως των καταληκτικών συμπερασμάτων.

The significance of angina pectoris in patients with aortic valve disease (AVD) and the need for coronary arteriography before valve replacement are controversial. The history of chest pain and coronary arteriographic findings were reviewed in 333 patients > or = forty years old, with AVD: 142 with aortic stenosis, 87 with mixed AVD and 104 with aortic regurgitation. The prevalence of coronary artery disease (CAD) was similar among different types of AVD. Angina pectoris was more frequent in patients with aortic stenosis (56%) and mixed AVD (53%) than in patients with aortic regurgitation (24%) (p < 0.0001). Similar results were found in patients with and without CAD. Twenty-six of 95 (27%) patients with CAD had no chest pain at all. The absence of any chest pain in CAD patients was more frequent in those > or = sixty years old than in those < sixty (p < 0.05). Thus, since a significant number of patients had CAD in the absence of any chest pain, the authors recommend coronary arteriography for all patients > or = forty years of age before aortic valve replacement.

The Ec peptide (PEc) of insulin-like growth factor 1 Ec (IGF-1Ec) induces human mesenchymal stem cell (hMSC) mobilization and activates extracellular signal-regulated kinase 1/2 (ERK 1/2) in various cells. The aim of the present study was to examine the effects of PEc on the mobilization and differentiation of hMSCs, as well as the possibility of its implementation in combination with transforming growth factor β1 (TGF-β1) for cartilage repair. The effects of the exogenous administration of PEc and TGF-β1, alone and in combination, on hMSCs were assessed using a trypan blue assay, reverse transcription-quantitative polymerase chain reaction, western blot analysis, Alcian blue staining, wound healing assays and migration/invasion assays. It was determined that PEc is involved in the differentiation process of hMSCs towards hyaline cartilage. Treatment of hMSCs with either PEc, TGF-β1 or both, demonstrated comparable cartilage matrix deposition. Furthermore, treatment with PEc in combination with TGF-β1 was associated with a significant increase in hMSC mobilization when compared with treatment with TGF-β1 or PEc alone (P<0.05). Thus, PEc appears to facilitate in vitro hMSC mobilization and differentiation towards chondrocytes, enhancing the role of TGF-β1.

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