ΤΟ ΕΥΕΡΓΕΤΗΜΑ ΤΗΣ ΑΠΟΓΡΑΦΗΣ

Ένα από τα σημαντικότερα προβλήματα που απασχόλησε τον Έλληνα νομοθέτη κατά τη σύνταξη του Αστικού Κώδικα ήταν και το ζήτημα της ευθύνης του κληρονόμου για τις υποχρεώσεις της κληρονομίας. Χαρακτηριστικά ο Μπαλής αναφέρει «ότι το ζήτημα της σχέσεως κληρονόμου προς τους κληρονομικούς πιστωτάς είναι, από νομοθετικής απόψεως σκοπούμενο, εν των δυσχερεστέρων προβλημάτων του Αστικού Κώδικος ». Με το θάνατο ενός ανθρώπου, δημιουργείται ζήτημα σχετικά με τη τύχη των δικαιωμάτων και των υποχρεώσεων που είχε ο ζούσε. Προκείμενου να μη δημιουργηθεί οποιοδήποτε πρόβλημα κυρίως στις συναλλαγές αλλά και στην κοινωνική ζωή εν γένει, το κληρονομικό δίκαιο, ρυθμίζει τις συνέπειες που επιφέρει ο θάνατος στα δικαιώματα και στις υποχρεώσεις του ανθρώπου. Στο δωδέκατο κεφάλαιο του κληρονομικού δικαίου, που τιτλοφορείται «κληρονόμος με απογραφή» άρθρα 1901-1912, ρυθμίζεται αυτός ο ιδιόρρυθμος θεσμός. Με την παρούσα διπλωματική εργασία, θα γίνει μια προσπάθεια να αναλυθεί όσο το δυνατόν πληρέστερα ο θεσμός της αποδοχής της κληρονομίας με το ευεργέτημα της απογραφής και τα ζητήματα που ανακύπτουν κατά την εφαρμογή και ερμηνεία των διατάξεων που τη ρυθμίζουν. Η παρούσα διπλωματική εργασία χωρίζεται σε τρία μέρη. Το πρώτο μέρος αφορά τον θεσμό της αποδοχής της κληρονομίας με το ευεργέτημα της απογραφής. Για να γίνει όμως κατανοητός ο θεσμός αυτός, προηγείται η ανάλυση της έννοιας του απλού κληρονόμου και η έκταση της ευθύνης του. Στη συνέχεια γίνεται εκτενής αναφορά στην έννοια του κληρονόμου με απογραφή καθώς και τον σκοπό που εξυπηρετείται με αυτόν τον θεσμό. Ακολουθεί η περιγραφή του τρόπο με τον οποίο γίνεται η αποδοχή της κληρονομίας με το ευεργέτημα της απογραφής και των συνεπειών που επέρχονται τόσο στην κληρονομιαία περιουσία όσο και στον εξ απογραφής κληρονόμο καθώς επίσης και στα δικαιώματα και στις υποχρεώσεις που δημιουργούνται για τον κληρονόμο με απογραφή. Το πρώτο μέρος ολοκληρώνεται με το τέλος του ευεργετήματος της απογραφής, τους τρόπους έκπτωσης και την παραίτηση από το ευεργέτημα καθώς και τυχόν αναζήτηση άλλων τρόπων λήξης του ευεργετήματος. Το δεύτερο μέρος, περιλαμβάνει την έρευνα που έχω διενεργήσει στα πλαίσια της παρούσας διπλωματικής εργασίας και αποτυπώνεται σε τέσσερις διαφορετικούς πίνακες. Στους πίνακες με αριθμούς (1) και (2) παρουσιάζονται σε αριθμούς το σύνολο των αποποιήσεων κληρονομιών και δηλώσεων αποδοχής με το ευεργέτημα της απογραφής, που έχουν κατατεθεί στα Ειρηνοδικεία Αθηνών και Πειραιώς, από το έτος 2013 έως και σήμερα. Στον πίνακα με αριθμό (3) παρουσιάζεται σε αριθμούς το σύνολο των αποποιήσεων κληρονομιών που έχουν κατατεθεί στα Ειρηνοδικεία της χώρας έως και το έτος 2017, σύμφωνα με ρεπορτάζ της εφημερίδας «Η ΚΑΘΗΜΕΡΙΝΗ». Στον πίνακα με αριθμό (4) παρουσιάζεται σε αριθμούς το σύνολο των αποποιήσεων κληρονομιών που έχουν κατατεθεί στο Ειρηνοδικείο Καλαμάτας έως και το έτος 2018, σύμφωνα με ρεπορτάζ της της ηλεκτρονικής εφημερίδας eleftheriaonline.gr. Τέλος, στο τρίτο μέρος, με το οποίο ολοκληρώνεται η παρούσα διπλωματική εργασία, γίνεται με μια κριτική αποτίμηση όσων προηγήθηκαν.This thesis, deals with the institution of acceptance of inheritance with the benefit of inventory and the issues that arise. The thesis is divided into three parts. The first part presents and analyzes the concept of the inheritor with the benefit of inventory and the purpose served by this institution. Furthermore, the following is a description of how the inheritance is accepted by the benefit of the inventory and its consequences. At the end of this part, are presented, the ways in which the benefit of the inventory ends. The second part is about the research carried out for the present thesis and there are four different tables. Finally, in the third and last part, a critical assessment of the institution of the benefit of inventory is made

A Novel Therapeutic Strategy for the Treatment of Glioma, Combining Chemical and Molecular Targeting of Hsp90a

Hsp90α's vital role in tumour survival and progression, together with its highly inducible expression profile in gliomas and its absence in normal tissue and cell lines validates it as a therapeutic target for glioma. Hsp90α was downregulated using the post-transcriptional RNAi strategy (sihsp90α) and a post-translational inhibitor, the benzoquinone antibiotic 17-AAG. Glioblastoma U87-MG and normal human astrocyte SVGp12 were treated with sihsp90α, 17-AAG and concurrent sihsp90α/17-AAG (combined treatment). Both Hsp90α gene silencing and the protein inhibitor approaches resulted in a dramatic reduction in cell viability. Results showed that sihsp90α, 17-AAG and a combination of sihsp90α/17-AAG, reduced cell viability by 27%, 75% and 88% (p < 0.001), respectively, after 72 h. hsp90α mRNA copy numbers were downregulated by 65%, 90% and 99% after 72 h treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG, respectively. The relationship between Hsp90α protein expression and its client Akt kinase activity levels were monitored following treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG. Akt kinase activity was downregulated as a direct consequence of Hsp90α inhibition. Both Hsp90α and Akt kinase levels were significantly downregulated after 72 h. Although, 17-AAG when used as a single agent reduces the Hsp90α protein and the Akt kinase levels, the efficacy demonstrated by combinatorial treatment was found to be far more effective. Combination treatment reduced the Hsp90α protein and Akt kinase levels to 4.3% and 43%, respectively, after 72 h. hsp90α mRNA expression detected in SVGp12 was negligible compared to U87-MG, also, the combination treatment did not compromise the normal cell viability. Taking into account the role of Hsp90α in tumour progression and the involvement of Akt kinase in cell signalling and the anti-apoptotic pathways in tumours, this double targets treatment infers a novel therapeutic strategy

Dissection of signal transduction mechanisms in response to chemotherapeutic agents in human cancer

In the context of the present PhD thesis, we investigated the anti-oncogenic properties of specific members of the benzoquinone ansamycin family of antibiotics in human bladder cancer cell lines of diverse malignancy grade and genetic background. The molecular techniques implemented in order to assess the biological effects of ansamycins on bladder cancer cell cultures in vitro were: fluorescence activated cell sorting (FACS) experiments, MTT tests, Western blottings, semi-quantitative RT-PCRs, electrophoretic mobility shift assays (EMSA), immunofluorescence and confocal microscopy, scratch wound assays, autophagy detection and 2DGE (2-dimensional gel electrophoresis), followed by proteomic analysis. The experimental data presented herein display the response mechanisms of bladder cancer cells due to drug-induced Hsp90 inhibition and the dose-dependent downregulation of its individual protein-clients. We have unveiled the multidimensional effect of Hsp90 inhibition upon the whole spectrum of cellular physiology by containment of various signaling cascades, furthermore resulting in the repression of the hallmark traits of cancer, while we also revealed new biomarkers for the clinical staging of human urinary bladder cancer. Conclusively, our experimental data reflect the prominent therapeutic value and clinical importance of benzoquinone ansamycins, denoting their central role in modern targeted chemotherapy of bladder cancer, and likely in other types of human malignancy.Στο πλαίσιο της συγκεκριμένης διατριβής μελετήθηκε η επίδραση επιλεγμένων μελών των ανσαμυκινών τύπου βενζοκινόνης σε καρκινικές κυτταρικές σειρές ανθρώπινης ουροδόχου κύστης διαφορετικού βαθμού κακοήθειας και γενετικού υποβάθρου. Οι μοριακοί χειρισμοί που πραγματοποιήθηκαν για την ανάλυση της επίδρασης των συγκεκριμένων παραγόντων σε in vitro καλλιέργειες κυτταρικών σειρών ουροδόχου κύστης περιελάμβαναν: αντιδράσεις κυτταρομετρίας ροής (FACS), δοκιμασίες προσδιορισμού κυτταρικής βιωσιμότητας (MTT), ανοσοστυπώματα Western, ημι-ποσοτικές αλυσιδωτές αντιδράσεις πολυμεράσης (RT-PCR), δοκιμασίες μεταβολής ηλεκτροφορητικής ικανότητας λόγω πρόσδεσης (EMSA), ανοσοκυτταροχημεία και συνεστιακή σαρωτική μικροσκοπία laser, δοκιμασίες «επούλωσης» πληγής, δοκιμασίες προσδιορισμού λυσοσωμικής ενεργότητας και ολική πρωτεωμική ανάλυση. Συνοπτικά, αναδείχθηκαν οι μηχανισμοί απόκρισης των καρκινικών κυττάρων ουροδόχου κύστης στην φαρμακο-επαγόμενη αναστολή της Hsp90 από τα αντιβιοτικά ανσαμυκίνης, καθώς και η δοσο-εξαρτώμενη μειορύθμιση των επιμέρους πρωτεϊνών-«πελατών» της. Αποκαλύφθηκε η πολυδιάστατη επίδραση της Hsp90 αναστολής σε ολόκληρο το φάσμα της κυτταρικής φυσιολογίας, με την ανάσχεση πολλαπλών σηματοδοτικών μονοπατιών, οδηγώντας σε καταστολή των φαινοτυπικών χαρακτηριστικών του καρκίνου, ενώ πραγματοποιήθηκε η αποκάλυψη νέων βιολογικών δεικτών για την κλινική σταδιοποίηση του καρκίνου της ουροδόχου κύστης. Τέλος, παρουσιάστηκαν πειραματικά στοιχεία τα οποία αντικατοπτρίζουν την υψηλή θεραπευτική αξία και κλινική σπουδαιότητα των ανσαμυκινών τύπου βενζοκινόνης, αναδεικνύοντας τον κεντρικό ρόλο τους στη σύγχρονη στοχευμένη θεραπεία του καρκίνου της ουροδόχου κύστης, και ενδεχομένως άλλων τύπων ανθρώπινης νεοπλασματικής εξαλλαγής

17-DMAG induces heat shock protein 90 functional impairment in human bladder cancer cells: knocking down the hallmark traits of malignancy

Heat shock protein 90 (Hsp90) is a molecular chaperone that maintains the structural and functional integrity of various protein clients involved in multiple oncogenic signaling pathways. Hsp90 holds a prominent role in tumorigenesis, as numerous members of its broad clientele are involved in the generation of the hallmark traits of cancer. 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) specifically targets Hsp90 and interferes with its function as a molecular chaperone, impairing its intrinsic ATPase activity and undermining proper folding of multiple protein clients. In this study, we have examined the effects of 17-DMAG on the regulation of Hsp90-dependent tumorigenic signaling pathways directly implicated in cell cycle progression, survival, and motility of human urinary bladder cancer cell lines. We have used MTT-based assays, FACS analysis, Western blotting, semiquantitative PCR (sqPCR), immunofluorescence, and scratch-wound assays in RT4 (p53wt), RT112 (p53wt), T24 (p53mt), and TCCSUP (p53mt) human urinary bladder cancer cell lines. We have demonstrated that, upon exposure to 17-DMAG, bladder cancer cells display prominent cell cycle arrest and commitment to apoptotic and autophagic cell death, in a dose-dependent manner. Furthermore, 17-DMAG administration induced pronounced downregulation of multiple Hsp90 protein clients and other downstream oncogenic effectors, therefore causing inhibition of cell proliferation and decline of cell motility due to the molecular “freezing” of critical cytoskeletal components. In toto, we have clearly demonstrated the dose-dependent and cell type-specific effects of 17-DMAG on the hallmark traits of cancer, appointing Hsp90 as a key molecular component in bladder cancer targeted therapy. © 2015, International Society of Oncology and BioMarkers (ISOBM)

17-Allylamino-17-demethoxygeldanamycin induces downregulation of critical Hsp90 protein clients and results in cell cycle arrest and apoptosis of human urinary bladder cancer cells

Background: 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinone ansamycin antibiotic, specifically targets heat shock protein 90 (Hsp90) and interferes with its function as a molecular chaperone that maintains the structural and functional integrity of various protein clients involved in cellular signaling. In this study, we have investigated the effect of 17-AAG on the regulation of Hsp90-dependent signaling pathways directly implicated in cell cycle progression, survival and motility of human urinary bladder cancer cell lines.Methods: We have used MTT-based assays, FACS analysis, Western blotting, semi-quantitative RT-PCR, immunocytochemistry and scratch-wound assay in RT4, RT112 and T24 human urinary bladder cancer cell lines.Results: We have demonstrated that, upon 17-AAG treatment, bladder cancer cells are arrested in the G1 phase of the cell cycle and eventually undergo apoptotic cell death in a dose-dependent manner. Furthermore, 17-AAG administration was shown to induce a pronounced downregulation of multiple Hsp90 protein clients and other downstream effectors, such as IGF-IR, Akt, IKK-α, IKK-β, FOXO1, ERK1/2 and c-Met, resulting in sequestration-mediated inactivation of NF-κB, reduced cell proliferation and decline of cell motility.Conclusions: In total, we have clearly evinced a dose-dependent and cell type-specific effect of 17-AAG on cell cycle progression, survival and motility of human bladder cancer cells, due to downregulation of multiple Hsp90 clients and subsequent disruption of signaling integrity. © 2010 Karkoulis et al; licensee BioMed Central Ltd

Relictual physiological ecology in the threatened land snail Codringtonia helenae: A cause for decline in a changing environment?

Land snails often exhibit intra-annual cycles of activity interspersed by periods of dormancy (hibernation/aestivation), accompanied by a range of behavioural and physiological adaptations to ensure their survival under adverse environmental conditions. These adaptations are useful to understand species-specific habitat requirements and to predict their response to environmental changes. We examined the seasonal physiological and biochemical composition patterns of the threatened land snail Codringtonia helenae, endemic to Greece, in relation to its behavioural ecology and climatic conditions. Fuel reserves (glycogen, lipids, proteins) and water were accumulated prior to aestivation, but subsequently were rapidly depleted. LDH exhibited substantial rise during aestivation, suggesting that anaerobic pathways may provide additional energy. The major outcome of our study was the unambiguous discrimination of the four life-cycle periods. Most remarkable was the clear distinction of the aestivation period, with hibernation, the other dormancy period, showing similarity with the two active periods but not with aestivation. We observed disassociation between behavioural and physiological responses and climatic conditions. The physiological responses of C. helenae were effective during hibernation, but only partly compensate the effect of adverse conditions during aestivation, since its aestivating behaviour is occasional and time limited. Perhaps, the behavioural ecology of Codringtonia is relictual and shaped during past environmental conditions. This constitutes an important extinction threat considering the current climatic trends and the deterioration of the habitat of that species due to human activities. © 2007 Elsevier Masson SAS. All rights reserved

Targeted inhibition of heat shock protein 90 disrupts multiple oncogenic signaling pathways, thus inducing cell cycle arrest and programmed cell death in human urinary bladder cancer cell lines

Background: Geldanamycin (GA) can be considered a relatively new component with a promising mode of action against human malignancies. It specifically targets heat shock protein 90 (Hsp90) and interferes with its function as a molecular chaperone.Methods: In this study, we have investigated the effects of geldanamycin on the regulation of Hsp90-dependent oncogenic signaling pathways directly implicated in cell cycle progression, survival and motility of human urinary bladder cancer cells. In order to assess the biological outcome of Hsp90 inhibition on RT4 (grade I) and T24 (grade III) human urinary bladder cancer cell lines, we applied MTT assay, FACS analysis, Western blotting, semi-quantitative (sq) RT-PCR, electrophoretic mobility shift assay (EMSA), immunofluorescence and scratch-wound assay.Results: We have herein demonstrated that, upon geldanamycin treatment, bladder cancer cells are prominently arrested in the G1 phase of cell cycle and eventually undergo programmed cell death via combined activation of apoptosis and autophagy. Furthermore, geldanamycin administration proved to induce prominent downregulation of several Hsp90 protein clients and downstream effectors, such as membrane receptors (IGF-IR and c-Met), protein kinases (Akt, IKKα, IKKβ and Erk1/2) and transcription factors (FOXOs and NF-κΒ), therefore resulting in the impairment of proliferative -oncogenic- signaling and reduction of cell motility.Conclusions: In toto, we have evinced the dose-dependent and cell line-specific actions of geldanamycin on cell cycle progression, survival and motility of human bladder cancer cells, due to downregulation of critical Hsp90 clients and subsequent disruption of signaling -oncogenic- integrity. © 2013 Karkoulis et al; licensee BioMed Central Ltd

Relictual physiological ecology in the threatened land snail Codringtonia helenae: A cause for decline in a changing environment?

Land snails often exhibit intra-annual cycles of activity interspersed by periods of dormancy (hibernation/aestivation), accompanied by a range of behavioural and physiological adaptations to ensure their survival under adverse environmental conditions. These adaptations are useful to understand species-specific habitat requirements and to predict their response to environmental changes. We examined the seasonal physiological and biochemical composition patterns of the threatened land snail Codringtonia helenae, endemic to Greece, in relation to its behavioural ecology and climatic conditions. Fuel reserves (glycogen, lipids, proteins) and water were accumulated prior to aestivation, but subsequently were rapidly depleted. LDH exhibited substantial rise during aestivation, suggesting that anaerobic pathways may provide additional energy. The major outcome of our study was the unambiguous discrimination of the four life-cycle periods. Most remarkable was the clear distinction of the aestivation period, with hibernation, the other dormancy period, showing similarity with the two active periods but not with aestivation. We observed disassociation between behavioural and physiological responses and climatic conditions. The physiological responses of C. helenae were effective during hibernation, but only partly compensate the effect of adverse conditions during aestivation, since its aestivating behaviour is occasional and time limited. Perhaps, the behavioural ecology of Codringtonia is relictual and shaped during past environmental conditions. This constitutes an important extinction threat considering the current climatic trends and the deterioration of the habitat of that species due to human activities. © 2007 Elsevier Masson SAS. All rights reserved

Targeted inhibition of heat shock protein 90 disrupts multiple oncogenic signaling pathways, thus inducing cell cycle arrest and programmed cell death in human urinary bladder cancer cell lines

Abstract Background Geldanamycin (GA) can be considered a relatively new component with a promising mode of action against human malignancies. It specifically targets heat shock protein 90 (Hsp90) and interferes with its function as a molecular chaperone. Methods In this study, we have investigated the effects of geldanamycin on the regulation of Hsp90-dependent oncogenic signaling pathways directly implicated in cell cycle progression, survival and motility of human urinary bladder cancer cells. In order to assess the biological outcome of Hsp90 inhibition on RT4 (grade I) and T24 (grade III) human urinary bladder cancer cell lines, we applied MTT assay, FACS analysis, Western blotting, semi-quantitative (sq) RT-PCR, electrophoretic mobility shift assay (EMSA), immunofluorescence and scratch-wound assay. Results We have herein demonstrated that, upon geldanamycin treatment, bladder cancer cells are prominently arrested in the G1 phase of cell cycle and eventually undergo programmed cell death via combined activation of apoptosis and autophagy. Furthermore, geldanamycin administration proved to induce prominent downregulation of several Hsp90 protein clients and downstream effectors, such as membrane receptors (IGF-IR and c-Met), protein kinases (Akt, IKKα, IKKβ and Erk1/2) and transcription factors (FOXOs and NF-κΒ), therefore resulting in the impairment of proliferative -oncogenic- signaling and reduction of cell motility. Conclusions In toto, we have evinced the dose-dependent and cell line-specific actions of geldanamycin on cell cycle progression, survival and motility of human bladder cancer cells, due to downregulation of critical Hsp90 clients and subsequent disruption of signaling -oncogenic- integrity.</p