Religious Imageries of Pilgrims from Przeworsk: Making Pilgrimage to the Shrine of Our Lady of Consolation at Jodłówka

My paper will provide an account of the religious imageries (T. Csordas) and practices of Catholic devotees from the Basilica of the Holy Spirit with whom I made pilgrimage on foot to the Shrine of Our Lady of Consolation at Jodłówka in August 2017. My account positions those imaginaries and practices within a broader contextual spectrum in order to move beyond events or conversations which were directly connected with the pilgrimage. To gain a better understanding of the religious needs of the pilgrims I spent time with some of them afterwards. Among other things, I attended masses involving healing services and charismatic prayer meetings. This way I was able to observe the important of sensory-based practices related to a belief in the porous self (Ch. Taylor). The devotees express that belief by, on the one hand, viewing themselves as being vulnerable to evil powers, and, on the other hand, by believing that they can remedy this danger by opening up to the influence of the Holy Spirit and by using water or exorcised oil blessed during a healing service. My paper will demonstrate the various ways in which belief in the porous self becomes objectivised, and its importance within the religious imageries of that group of devotees

Healing Chains, Relationships of Power and Competing Religious Imageries in the Monastery of Saints Kosmas and Damian in Kuklen (Bulgaria)

This article offers an anthropological analysis of a conflict over the use of a set of 'healing chains' and other focal objects kept in the Orthodox Christian monastery of Saints Kosmas and Damian in Kuklen, Bulgaria. In a nutshell, the conflict captures the leading religious imageries propagated by the custodians of the monastery on the one hand, and the spiritual leaders of a new religious movement, so-called Deunovians, on the other. The analysis helps situate some of the significant changes currently affecting the religious culture of Orthodox Christians in Bulgaria within a broader social and cultural context

Revisiting CDK Inhibitors for Treatment of Glioblastoma Multiforme

Despite extensive efforts and continual progress in research and medicine, outcomes for patients with high-grade glioma remain exceptionally poor. Over the past decade, research has revealed a great deal about the complex biology behind glioma development, and has brought to light some of the major barriers preventing successful treatment. Glioblastoma multiforme (GBM) (stage 4 astrocytoma) is a highly dynamic tumour and one of the most extreme examples of intratumoural heterogeneity, making targeting with specific therapeutics an inefficient and highly unpredictable goal. The cancer stem cell hypothesis offers a new view on the possible mechanisms dictating the heterogeneous nature of this disease and contributes to our understanding of glioma resistance and recurrence. Revealing cell division characteristics of initiating cell populations within GBM may represent novel treatment targets and/or the effective repurposing of existing therapies. In this review, we discuss the potential role of targeting the cyclin-dependent kinases (CDKs) driving this specific population. We also describe developments using multi-omic approaches that may aid in stratifying patient populations for CDK inhibitor therapy

The Atypical Cell Cycle Regulator Spy1 Suppresses Differentiation of the Neuroblastoma Stem Cell Population

Neuroblastoma is an aggressive pediatric cancer originating embryonically from the neural crest. The heterogeneity of the disease, as most solid tumors, complicates diagnosis and treatment. In neuroblastoma this heterogeneity is well represented in both primary tumours and derived cell lines and has been shown to be driven by a population of stem-like tumour initiating cells. Resolving the molecular mediators driving the division of this population of cells may indicate effective therapeutic options for neuroblastoma patients. This study has determined that the atypical cyclin-like protein Spy1, recently indicated in driving symmetric division of glioma stem cells, is a critical factor in the stem-like properties of neuroblastoma tumor initiating cell populations. Spy1 activates Cyclin Dependent Kinases (CDK) in a manner that is unique from classical cyclins. Hence this discovery may represent an important opportunity to design CDK inhibitor drugs to uniquely target subpopulations of cells within these aggressive neural tumours

Novel Approach in Resolving the Mechanism Behind Brain Tumour Heterogeneity and Therapy Response

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumour with 5-year survival rates of less than 10%. Data supports that select cell populations within the tumour mass, referred to as Brain Tumour Initiating Cells (BTICs), are the drivers of GBM growth. While the true origin of these cells is debatable, physiologically these cells possess immature properties of normal neural stem cells. They are highly resistant to drug treatment, radiation and form tumours at a high rate when transplanted into mice. Adding to GBM complexity is the fact that not all the tumours are the same; most patients can be grouped into at least 3 different ‘subtypes’ of GBM using modern genetic tools. This project builds on exciting data demonstrating that a unique cell cycle regulator, Spy1 (or RINGO by other groups) is found in normal neural stem cells during brain development, yet, it controls expansion of BTICs. Understanding which specific BTIC populations within the GBM heterogeneous mass are driven by Spy1 and whether this is subtype dependent, may represent novel and effective treatment strategies. Utilizing brain tumour patient-derived cells of genetically determined GBM subtype and based on expression of well defined BTIC markers, I established a BTIC bank through application of different cell sorting techniques. This approach allows me to further dissect the role of Spy1 in those dangerous cell populations, both in vitro and in vivo, to understand how specific BTICs grow, divide, and what role they play in each of the GBM subtypes, which is the aim of this project. Primary results revealed a strong association of specific combinations of markers within distinct GBM subtypes and significant correlation of Spy1 levels with specific BTIC populations, which sets a potential direction for assessment of new therapy targets and effective treatment strategies against GBM

Role of Mechanical and structural properties of GBM microenvironment in tumour aggressiveness and therapy resistance

Glioblastoma Multiforme (GBM) is the most common and most aggressive type of brain cancer, accounting for 12 to 15% of all intracranial tumours. With a median survival of three to six months for patients with recurrent GBM, there is an urgent need for advancements in the study, diagnosis, and treatment of GBM. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a method of non-invasive tumour analysis that can create a description of mechanical and fluid stress properties of a tumour. DCE-MRI has the potential to couple static mechanical descriptions of analyzed tumours to the flow and fluxes of the fluids in the tumour, thus generating a complete picture of the local stresses, pressure, and flows in and around an embedded tumour. By studying the expression of Vinculin and Hyaluronic Acid (HA), notable stress response markers, in the brain tumour sections; it is the aim of this project to establish protein signatures that correlate with DCE-MRI readings to provide a tool for more effective and detailed diagnosis of GBM. Furthermore, in order to study the tumour with its stress responses to changes in extracellular matrix pressures in a dynamic, three-dimensional setting, we employed brain tumour organoid (BTO) cultures. BTOs provide an in-vitro modelling method that more accurately represents in vivo tissue organization. Through control of microenvironmental factors which an organoid is suspended in, solid stresses can be manipulated and responses studied. As a result, the organoid model can reinforce characterization of cellular responses found when studying tumours. Preliminary results suggest that varying extracellular matrix stiffness results in quantifiable and correlated changes in invasion, aggressiveness and marker protein levels. Defying the local stress factors and their effects on tumour proliferation, aggressiveness marker expression and drug treatment response can help in designing better diagnostic tools and more effective therapeutic strategies

The Novel Role of GABAB and CXCR4 in Medulloblastoma

Medulloblastoma (MB) is the most common malignant pediatric brain tumor and it occurs in 16-25% of diagnosed cases, with a higher incidence in children aged 1 to 9 years old. The current standard of care consists of multiple stages of therapy including surgery, irradiation, and chemotherapy. However, a subset of tumors with a still devastating prognosis remains. Metabotropic receptors are G-protein coupled receptors (GPCRs) that act as second messengers. Γ-aminobutyric acid B receptors (GABAB) and C-X-C chemokine receptor type 4 (CXCR4) are metabotropic receptors that belong to the C-family of GPCRs and are activated by the neurotransmitters, γ-aminobutyrate (GABA) and stromal-cell derived factor; SDF-1 (CXCL12), respectively. GABAB receptors are heterodimers where GABA binds to a B1 subunit, and the B2 subunit is coupled to G-proteins regulating activities of the Ca2+ channels, K+ channels, and adenylyl cyclase (AC). Previous studies showed that CXCR4 is highly expressed by glial and neuronal cells in the central nervous system (CNS) and GABAergic neurons. Evidence shows that CXCR4 is overexpressed in MB and upon administration of a CXCR4 antagonist significantly decreased the cell proliferation rate in Type II MB. Evidence also proved that CXCR4 and GABAB­ can crosstalk and GABAB was found to be highly expressed in Type II – MB showing increased Ca2+ levels and protein receptor localization. Current results show that upon administration of the GABAB agonist; baclofen increased cell proliferation in Type II MB cells. Moreover, immunofluorescence showed increased levels of GABAB during mitotic division. In conclusion, by administering the antagonist; phaclofen would enhance the efficacy of chemotherapeutic treatments on MB patients by decreasing the proliferation rate of the aggressive tumors