Τμήμα Βιολογικών Επιστημών / Department of Biological Scienceshttp://gnosis.library.ucy.ac.cy:80/handle/7/617262024-03-29T11:01:29Z2024-03-29T11:01:29ZThe PINK1/Parkin-dependent mitophagy pathway and its role in Parkinson’s diseaseTheodosiou, Irenehttp://gnosis.library.ucy.ac.cy:80/handle/7/661332024-02-28T09:08:26Z2024-01-01T00:00:00ZThe PINK1/Parkin-dependent mitophagy pathway and its role in Parkinson’s disease
Theodosiou, Irene
Parkinson's disease is the second most prevalent neurodegenerative disease, surpassed only by Alzheimer’s disease. The disease is relentless, progressive, and incurable, and there is a great need to understand its causes and develop new treatments. A distinctive pathology in most cases of Parkinson’s disease is the loss of dopaminergic neurons in the Substantia Nigra. This depletion of dopaminergic neurons has been mostly part due to the appearance of Lewy bodies containing misfolded, toxic α-synuclein within. Most recently, Parkinson’s disease has also been linked to the mitophagy pathway since genetic studies identified numerous genes linked to this disease. The processes that keep mitochondria networks healthy can be impaired in Parkinson’s disease, and mitochondria are unable to sustain proper neuronal function. Mitophagy is a selective autophagy process which targets the mitochondria for degradation. Parkinson’s disease has been shown to be linked with one of the three distinct pathways of mitophagy namely the PINK1/Parkin-dependent pathway. In this bibliographical review we will extensively discuss the work leading to delineation of this pathway as well as more recent work involving novel targeting approaches for the development of a potential new drug to halt the neurodegeneration of dopaminergic neurons and therefore treat Parkinson’s disease.
2024-01-01T00:00:00ZProstate Cancer Organoids in the Fight Against Prostate CancerPanteli, Mariahttp://gnosis.library.ucy.ac.cy:80/handle/7/661272024-02-28T09:08:27Z2023-12-13T00:00:00ZProstate Cancer Organoids in the Fight Against Prostate Cancer
Panteli, Maria
Ο καρκίνος του προστάτη είναι μία από τις κυριότερες ασθένειες που αυξάνουν τα ποσοστά νοσηρότητας και θνησιμότητας στους άνδρες παγκοσμίως. Παρά τη µεγάλη ετερογένεια µεταξύ των όγκων και των ασθενών, ο καρκίνος του προστάτη είναι, στις περισσότερες περιπτώσεις, ευαίσθητος στα ανδρογόνα στα πρώιµα στάδια και εποµένως µπορεί να αντιµετωπιστεί µε θεραπεία στέρησης ανδρογόνων ή/και χειρουργικό ευνουχισµό. Ωστόσο, σε ορισμένες περιπτώσεις, μπορεί να γίνειανθεκτικός στα ανδρογόνα, κυρίως λόγω της πειρατείας διαφόρων κυτταρικών μονοπατιών, όπως το μονοπάτι AR και/ή το μονοπάτι JAK/STAT, καθώς και λόγω άλλων γενετικών και επιγενετικών παραγόντων.Ως αποτέλεσμα, ο όγκος αποκτά έναν πιο επιθετικό, μεταστατικό, ανθεκτικό στον ευνουχισμό φαινότυπο.Αυτή η μορφή καρκίνου του προστάτη παραμένει μη θεραπεύσιμη. Κυτταρικές σειρές και ζωικά µοντέλα έχουν χρησιµοποιηθείεκτενώς για την ανακάλυψη διαγνωστικών βιοδεικτών καθώς και για την ανάπτυξη νέων θεραπευτικών προσεγγίσεων. Ωστόσο, τα τελευταία χρόνια αναπτύσσονται οργανοειδή του καρκίνου του προστάτη για την ακριβέστερη αναπαράσταση του μικροπεριβάλλοντος του όγκου και της τρισδιάστατης φύσης του. Η παρούσα βιβλιογραφική ανασκόπηση επικεντρώνεται στην παρουσίαση της συμβολής των οργανοειδών του καρκίνου του προστάτη στον τομέα. Πιο συγκεκριμένα, θα συζητήσουμε τη χρήση των οργανοειδών του καρκίνου του προστάτη α) στον προσδιορισμό διαγνωστικών βιοδεικτών, β) στην επαναπροσδιορισμό φαρμάκων και γ) στην ανάπτυξη νέων θεραπευτικών προσεγγίσεων. Αυτή η ανασκόπηση δείχνει ότι η χρήση των οργανοειδών, αν και βρίσκεται ακόμη σε νηπιακό στάδιο, ανοίγει το δρόμο για την ιατρική ακριβείας και διευκολύνει τη δοκιμή φαρμάκων με βάση την προσαρμογή στον ασθενή, για να αναπτυχθούν καλύτερες θεραπευτικές μεθόδοι.; Prostate Cancer is one of the leading diseases that increase morbidity and mortality rates in men worldwide. Despite high intertumoral and inter-patient heterogeneity, prostate cancer is, in most cases, androgen-sensitive at its early stages and thus can be treated using androgen deprivation therapy and/or surgical castration. However, in certain cases, it can become resistant to androgens, primarily due to hijacking of several cellular pathways, such as the AR pathway and/or the JAK/STAT pathway, as well as due to other genetic and epigenetic factors. As a result, the tumor acquires a more aggressive, metastatic, castration-resistant phenotype. This form of prostate cancer remains uncurable. Cell lines and animal models have been used extensively for the discovery of diagnostic biomarkers as well as for the development of novel therapeutic approaches. However, in the last few years, prostate cancer organoids are being developed to recapitulate the tumor microenvironment and its 3-dimensional nature, more precisely. This bibliographical review focuses on presenting the contribution of prostate cancer organoids to the field. More specifically, we will discuss the use of Prostate Cancer Organoids
in the a) identification of diagnostic biomarkers, b) drug repurposing and c) development of novel therapeutic approaches. This review shows that the use of organoids, even though still at its infancy, paves the way to precision medicine and facilitates drug testing in a patient-tailored manner, to achieve better treatments.
2023-12-13T00:00:00ZNovel therapeutic approaches targeting the molecular mechanisms governing SARS-CoV-2 infectionChasikos, Ioannishttp://gnosis.library.ucy.ac.cy:80/handle/7/660962024-02-28T09:08:27Z2023-01-01T00:00:00ZNovel therapeutic approaches targeting the molecular mechanisms governing SARS-CoV-2 infection
Chasikos, Ioannis
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing worldwide pandemic of Coronavirus Disease 2019 (COVID-19), which remains a public health concern despite the successful rollout of effective vaccines. This is why several therapeutic strategies targeting molecular mechanisms of SARS-CoV-2 infection have been developed; they target viral entry into host cells, immune dysregulation, replication of the viral genome and proteolytic processing of the viral products. Targeting is achieved using multiple approaches including small inhibitory molecules, monoclonal antibodies and immunomodulatory drugs. Despite the existence of currently successful treatments, there is a growing need for novel therapeutic strategies due to the continuous evolution of new SARS-CoV-2 variants, capable of developing resistance to approved antivirals and due to the immune response elicited from vaccinations. These include further inhibition of viral targets, the use of antibody-mimetics, host-directed therapies and nucleic acid-based therapeutics. This bibliographical review attempts to provide a comprehensive understanding of how these novel therapeutic strategies elicit their antiviral effects, the advantages and disadvantages regarding their application and the challenges faced during their development and use.
2023-01-01T00:00:00ZMechanisms underlying Trastuzumab Resistance in HER2-positive (HER2+) Breast Cancer and potential therapeutic approachesTheodorou, Troodiahttp://gnosis.library.ucy.ac.cy:80/handle/7/660372024-02-28T09:08:28Z2023-12-13T00:00:00ZMechanisms underlying Trastuzumab Resistance in HER2-positive (HER2+) Breast Cancer and potential therapeutic approaches
Theodorou, Troodia
HER2-positive (HER2+) breast cancer is characterized by overexpression of HER2 (Human Epidermal Growth Factor Receptor 2) protein on the surface of cells in the breast's ducts or lobes. HER2 overexpression creates an overabundance of homo- and/or heterodimers with other family members, and triggers activation of PI3K/Akt and MAPK signalling pathways, resulting in uncontrolled cell growth and proliferation. Past studies have shown that HER2 overexpression correlates with aggressiveness, higher relapse risk, and poor long-term survival. The incorporation of the monoclonal antibody trastuzumab into chemotherapy has dramatically improved treatments. Trastuzumab prevents HER2 homo- and/or heterodimerization, and promotes HER2 endocytosis, ubiquitination, and proteolytic degradation, resulting in inhibition of the HER2 signalling pathway and HER2-induced cellular responses. However, trastuzumab resistance which mainly develops in the metastatic setting, is a major clinical problem. This bibliographical review primarily focuses on presenting three molecular mechanisms, through which trastuzumab resistance arises leading to continuous activation of the HER2 signalling pathway. The first mechanism involves overexpression of CMTM6, leading to decreased HER2 ubiquitination, resulting in increased cell viability, proliferation and invasion, and decreased apoptosis. The second mechanism involves underexpression of CMTM7, caused by miR-182-5p and leading to Rab-5A inactivation, resulting in the prevention of HER2 degradation. The third mechanism involves the overexpression of TRAF4 E3 ubiquitin ligase that prevents SMURF2 E3 ubiquitin ligase from interacting and ubiquitinating HER2, resulting in continuous activation of the HER2 signalling pathway and increased cell viability and tumour volume. In addition, this review discusses several therapeutic approaches to overcome trastuzumab resistance, including a) the use of adavosertib to reduce CMTM6 expression, b) the use of the miR-182-5p inhibitor to prevent the reduction of CMTM7 expression and c) β-escin, as an alternative drug. Currently, approved therapies are focused on the use of trastuzumab in combination with pertuzumab or ado-trastuzumab emtansine (T-DM1) antibodies. This review showed that continued research to identify the optimal combined therapy holds promise for enhancing overall survival in HER2+ breast cancer patients.
2023-12-13T00:00:00Z