This thesis rereads central texts of Paul’s letters to demonstrate that Paul’s speech about God, Jesus Christ, and the Spirit is intricately intertwined so that talk about any one of the three (God, Jesus, or the Spirit) implies reference to all of them together (God, Jesus, and the Spirit). The first part of the Introduction describes how the current landscape of Pauline scholarship has largely given up this way of articulating the dynamics of Paul’s God-, Christ-, and Spirit-discourse. Eschewing explicitly trinitarian language in favor of other conceptualities, much recent Pauline scholarship has opted for discussing the relationship between God and Jesus in terms of ‘high’ or ‘low’ christology. After summarizing this trend, the second part of the Introduction describes trinitarian theologies as representing a better approach that will serve to open a fresh angle on Paul, despite its conceptual difference from Paul’s own speech. The next four chapters defend that supposition with detailed exegesis. Chapter 1 considers how the identity of God is shaped by Paul’s christology: God’s identity is only what it is in relation to Jesus. Chapters 2 and 3 consider the converse: how the identity of Jesus is shaped by his relation to God. These latter two chapters also rebut the charge that Paul’s alleged ‘subordinationist’ christology renders a trinitarian, relational reading of the divine identity untenable. Drawing on the conclusion found in the history of trinitarian theologies that the oneness or unity between God and Jesus does not come into conflict with the distinction between God and Jesus, Chapters 2 and 3 argue that the mutuality that exists between God and Jesus is asymmetrical but not for that reason graspable with the concept of ‘subordinationism’. Chapter 4 brings the Spirit into the mutual, reciprocal relationship between God and Jesus. The Spirit’s identity is derived from God and Jesus’; yet the Spirit is also involved in the sequence of events whereby God and Jesus are identified. The Spirit’s identity is relationally determined, but also God and Jesus are who they are only by virtue of the Spirit’s agency which is exercised by God in the resurrection of Jesus. In this way, despite its historical distance from Paul and its different idiom, trinitarian theology is shown to illumine a way through interpretive difficulties in Paul’s letters that the more recent concepts of ‘high’ and ‘low’ christology have hitherto been unable to illumine.

This study examines the relationship between scriptural authority and the life of faith in the prominent English Reformed orthodox theologian, John Owen. While aspects of Owen’s argument have caught the attention of scholars across a relatively diverse range of fields, no full-length historical treatment of this theme has yet appeared, and many of its distinctive features remain unexplored. The thesis particularly seeks to show how Owen creatively drew upon an ‘ecumenical’ dogmatic and metaphysical heritage to restate and refine the traditional Reformed position on scriptural authority, sensitive to intellectual developments in his own late seventeenth-century context. The broader intention is to enrich the expanding scholarly interest in Owen’s thought, alongside Puritan, Reformed orthodox thought in general, and also, perhaps, to serve as a resource for those approaching this general subject from other disciplines. The thesis concentrates on Owen’s Reason of Faith (1677), in conversation with his wider mature corpus. After an introduction which presents the background and parameters for the study, chapter 2 introduces the central themes of Reason of Faith. It points to Owen’s engagement with contemporary apologists and their deleterious reliance on well-worn rational arguments or ‘evidences’ as the foundation for faith. Chapters 3, 4 and 5 examine Owen’s own constructive position. While recognising and incorporating the value of ‘objective evidence’ in faith, Owen offers his own critical reformulation that preserves the integrity of faith as something resting exclusively on divine testimony. Chapters 3 and 4 focus upon the role of subjective divine illumination in the perception of natural truths (chapter 3), and the gracious truths revealed in scripture (chapter 4), noting especially Owen’s use of habitual terminology derived from scholastic thought. Chapter 5 examines the critical function of scripture’s ‘light’ and ‘power’ as the divine ‘evidence’ or ‘objective testimony’ which appeals uniquely to the regenerated and elevated faculties, and secures faith. The chapter also aims to observe how Owen relates this authority to important christological and redemptive themes emerging elsewhere in his thought, not least the restored ‘image of God’. The final two chapters shift attention to related features of scripture. Honouring the essentially confessional nature of scripture’s authority, chapter 6 shows how Owen locates scripture within a covenantal frame, drawing upon a traditional account of inspiration. Chapter 7 explores the relationship Owen sees between scriptural authority and perspicuity, which enables an immediate, ongoing relationship between the rule of Christ and his church, and regulates the way it is read and understood by believers using the means of grace. The conclusion summarises Owen’s unique contribution to the Reformed consensus on scriptural authority in the face of an increasing fragmentation of confessional orthodoxy on this issue. Three compact appendices are added: Appendix A discusses Owen’s reliance on peripatetic cognitive metaphysics; Appendix B provides a survey of key historical developments in the Augustinian doctrine of natural illumination; Appendix C addresses some historiographical problems pertaining to inspiration in Reformed orthodoxy and Owen in particular.

In On Christian Teaching, Saint Augustine writes, “Just and holy living depends on being a good judge of things.” This brief sentence lucidly articulates the importance that judgment plays in Augustine’s thought. This thesis is the first full-length study of how he understands the distinct role of the Holy Spirit in judgment. I argue that judgment denotes both the discernment of a thing’s nature and evaluation of it; and we become good judges only as we are re-ordered by the love which is, in Augustine’s favourite pneumatological verse, “poured into our hearts by the Holy Spirit” (Romans 5:5). I analyse this transformative work of the Spirit according to two broad categories: first, the Spirit re-orders our relation to creation principally by uniting us to the Word, the second person of the Trinity, in whom all things are created, and so we are able to discern a thing’s nature and evaluate it according to God’s purposes in creation; and, second, the Spirit re-orders our relation to time, as we patiently endure this troublous life as pilgrims hoping for eternal Sabbath rest; within this eschatological horizon situated in the age between Christ’s first coming and his return, we restrain ourselves from making both unfounded and unnecessary judgments as we defer to God’s final judgement. This thesis is divided into two parts. In the first part, on the “theory” of judgment, I explicate the consistent relation throughout Augustine’s corpus between pneumatology, judgment and ethics (chapter one). I then proceed to trace out his account of how the gift of the Spirit’s love perfects our judgment by re-ordering our relation to creation, and, conversely, how lust distorts it. A right relation to creation turns on taking up our middle place: below God, next to our neighbours, and above nature (chapter two). In the second part, on the “practice” of judgment, I focus first on other-judgment, especially the role of mercy (chapter three), and then in the fourth and final chapter I turn to self-judgment, including a lengthy consideration of the nature and role of conscience (chapter four). For Augustine, then, it is only by the Spirit’s love that we are made good judges, and, simultaneously, it is only when we are good judges that our love conforms to the truth both of God’s good creation and of our in-between age.

Cyril of Alexandria left to posterity a sizable body of exegetical literature. This thesis attempts to reconstruct his theology of Scripture in order to suggest that his exegetical practice is inseparable from, and must be interpreted in light of, his overarching theological vision. I argue that the most important intellectual factor shaping his exegesis is his Christologically focused, pro-Nicene Trinitarianism, an inheritance that he received from fourth-century authors. Cyril’s appropriation of pro-Nicene thought is evident in his theology of revelation and his theology of exegesis. Revelation, in his understanding, proceeds from the Father, through the Son, and in the Spirit, following the order of Trinitarian relations. Moreover, this pattern applies to the inspiration of Scripture as well, insofar as inspiration occurs when the Son indwells human authors by the Spirit and speaks the words of the Father. Corresponding to this movement of God towards humanity in revelation is humanity’s growth in understanding that occurs according to a reverse pattern—in the Spirit, through the Son, unto the Father. This scheme applies broadly to Cyril’s soteriology, but also to his understanding of exegesis, since he regarded biblical interpretation as a means of participating in the divine life. More specifically, this Trinitarian pattern implies that the Spirit is required to read Scripture properly, and that in the act of interpretation the Spirit directs the reader to a Christological reading of Scripture, through which the believer gains a limited but genuine apprehension of the Trinitarian mystery. This process continues until the final eschatological vision when the types and riddles of Scripture will be done away with in light of the overwhelming clarity of the vision of the Father.

This thesis seeks an orderly set of theological reflections on the declaration that “God is light” (1 Jn. 1:5). Such talk of divine light, this study argues, must begin with the doctrine of God, namely, with God's light in se and his “shining forth” ad extra towards creatures in the darkness of sin and death. This work therefore follows a precise pathway in expounding this theme. Chapter 1 offers a brief survey of the historical and scriptural uses of the concept of light in order to fix its linguistic and conceptual boundaries. Chapter 2 seeks to reflect upon God's light as the light of his own radiant triune identity, as well as offering a preliminary examination of God's economic, covenantal shining forth to creatures. Chapter 3 gives a much more detailed rehearsal of this act of shining forth by an account of God's light as manifest in the economy of his works with which he lovingly elects, reconciles, and illuminates creatures. Chapter 4 proposes that with the treatment of God's shining forth there belongs a treatment of the light of the church called out of darkness, gathered into the “marvelous light” of God, and set to proclaiming the “excellencies” of God. Chapter 5 concludes this study by examining what bearing the reality of God's shining forth as Father, Son, and Holy Spirit might have on the work and call of theology as an activity of the 'illumined mind'.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

This thesis will argue that by applying a hermeneutic of performance to biblical narratives, religious dramatic texts and Anglican liturgies we are able to encounter the divine as an immanent and transcendent presence in theatrical performance. Performance, and theatricality, create realities beyond our quotidian experience and provide a context for such encounters. To explore these encounters I consider biblical texts, where God is present and active in a narrative, dramatic texts where God is a character on stage and Christian liturgies where God is active as first person of the trinity, passive as object of worship, or supremely in the Eucharist, present as Jesus. All will be examined through the twin lenses of performance as an end and theatricality as the means to such an end. Theatrical performance is conditional upon multiple dynamics of action and reaction, feedback and response between both actors and audience which constantly modulate its process. Although capable of repetition, a performance remains unique and possessed of its own truth – however interpreted, Hamlet remains Hamlet. In performance actors become characters, each working with audiences to create and participate in different realities. This is the single most important application of theatricality. In performance, all characters and audience are of equal value and within the framework of a performance can shape and change what happens. ‘Upstaging’ of any character, by any character is always possible. This means that outcomes may be expected but can never be guaranteed. God viewed as a character must be subject to the same constraints as other characters. This raises theological problems. In the biblical narrative of Moses, God is upstaged by Aaron casting the Golden Calf, and by Moses’ post hoc rejection of divine forgiveness. Once God appears on stage his divinity is at risk by being, or perceived as being a human playing at being God, so finite and idolatrous. In liturgical texts God is the object of worship, but when worship includes elements of performance and theatricality, God, Jesus and congregations are all potential performers raising the theological spectre of authentic ‘liturgical celebration’ becoming theatrical ‘imaginative representation’. However, the different realities afforded by performance and theatricality allow mutual liminalities as God and humanity cross thresholds into each others’ presence sharing and shaping events. In all the texts examined there are events where transgression and conflict render them susceptible to becoming tragedies. As a character in their performance God’s impassibility is threatened and he must bear responsibility for their outcomes with their apparent loss of redemptive hope. As God becomes a character in human stories (Moses, cycle plays) his immanence affects their outcomes, but as humans become characters in divine stories (the Eucharist) they enter moments of transcendence. In their mutuality, realities created by performance and theatricality offer transformative experiences of truth and redemptive hope unique in themselves but unitive in their repetition.

Breast cancer is the most commonly occurring cancer worldwide, more than 2.26 million new cases occurred in women in 2020. Treatment for breast cancer is normally individualized to the patient based on the presence of different receptors, these receptors include HER2, progesterone, and estrogen. The presence of these receptors generally comes with an amenable prognosis, and a wide array of available treatments. There are types of breast cancers that do not have any of these receptors and tend to be much more aggressive. This type of cancer is called triple negative and represents about 10 percent of all breast cancer occurrences in the United States. The lack of receptors makes this type of cancer extremely difficult to treat and generally comes with a poor prognosis. In the present study, we used triple negative breast cancer cell line MDA-MB231, which is known to use actin remodeling to evade immunologic response. These cells were treated with two novel, structurally similar flavonoids, CT1 and CT3 derived from an ethnobotanically recognized species of Chromolaena. CT1 and CT3 are extracted from the leaves of Chromolaena tacotana and then isolated and purified by chromatography. These compounds are used to treat cancer cells, at different concentrations that include 5, 10, 20, 40 and 80mM. MTT assays are used to determine their effect on cell viability, and the mechanism of action was analyzed by immunoblotting and TUNEL.. CT1 has a significantly stronger inhibitory effect on MDA-MB231 cell viability as compared to CT3. Preliminary analysis of the mechanism of action of CT1 has revealed that it neither follows the canonical intrinsic apoptotic pathway nor the extrinsic pathway that involves the activated form of c-JUN. By up-regulating actin, triple negative breast cancer is able to evade immunologic response and cancer treatment. CT1, a novel flavonoid extracted from the leaves of Chromoleana tacotana has shown cytotoxic effects against triple negative breast cancer cells effectively bypassing the actin response. The mechanism of action is currently under study.

Le récepteur de la progestérone (PR) est un acteur majeur du développement de la glande mammaire. Dans les cellules épithéliales normales, PR est exprimé sous deux isoformes PRA (94 kDa) et PRB (116 kDa) de façon équimolaire. Il est établi que celles-ci ont un impact important sur le développement des cancers du sein, mais leurs rôles dans l’évolution métastatique reste très mal connus. Le ratio d’expression PRA/PRB étant souvent déséquilibré dans les tumeurs mammaires, nous avons analysé le turnover des deux isoformes. Nous avons démontré que PRA et PRB sont les cibles de modifications post-traductionnelles dirigées par les MAPK qui tendent à stabiliser l’une ou l’autre isoforme de manière sélective. Ainsi, Erk1/2 (p42/44) inhibe la dégradation de PRB tandis que la p38 stabilise PRA. Il en résulte que le ratio PRA/PRB varie de façon importante en fonction des signalisations extracellulaires impliquant les facteurs de croissance et les cytokines inflammatoires souvent exacerbés dans les cancers. Pour mieux étudier les effets différentiels de PRA et PRB, nous avons établi un modèle cellulaire original exprimant de manière bi-inductible l’une ou l’autre isoforme de PR, à partir de la lignée cellulaire MDA-MB 231 provenant d’une métastase de cancer du sein. En étudiant les variations induites par PRA ou PRB sur le transcriptome de ces cellules, nous avons identifié les gènes cibles spécifiques de ces isoformes. Parmi-eux se trouvent de nombreux gènes impliqués dans les cancers, notamment agissant sur la prolifération, la survie et la motilité cellulaires comme uPA et PAI-1. De plus, en analysant la migration cellulaire, nous avons mis en évidence un effet pro-migratoire de PRB particulièrement important en absence d’hormone. En recherchant la cause de ces effets, nous avons découvert que PRB était colocalisé et interagissait avec la kinase d’adhésion focale (FAK) qu’il active au niveau des points d’adhésion focaux. Ces travaux soulignent l’incidence du ratio PRA/PRB et du statut du ligand sur les métastases du cancer du sein, aussi bien au niveau de la sélectivité transcriptionnelle que celui des régulations non génomiques impactant la migration cellulaire. Nous suggérons la possibilité de cibler les tumeurs mammaires par des antagonistes sélectifs de PR et des inhibiteurs des voies de signalisation des MAPK ou de FAK. / Progesterone receptor (PR) is a major actor of mammary gland development. PR is equally expressed as two main isoforms PRA (94 kDa) and PRB (116kDa) in the mammary gland epithelium. However, breast cancer progression has been associated with abnormalities of their expression ratio through undefined mechanisms. In this study, using a stably transfected cell line, we showed that PRA and PRB stabilizations are differentially regulated by Erk1/2 (p42/44) and p38 MAPKs respectively, leading to strongly influence PRA/PRB ratio. These results highlight the impact of growth factors and inflammatory cytokines on PRA/PRB imbalance in cancer cells. To study the differential effect of PR isoforms, we established an original bi-inducible cell line expressing either PRA and/or PRB. By analyzing variations induced by PRA and PRB on such cell transcriptomes, we identified the isoform-specific targets genes by DNA microarrays. Most of them are implicated in cancers, notably acting on cell proliferation, survival and motility. Furthermore, focusing our studies on cell migration, we showed that PRB acts as a pro-migratory factor particularly powerful in the absence of ligand. We discovered that PRB colocalized and interacted with the focal adhesion kinase (FAK) that was activated in focal adhesion points. Our results highlight the impacts of both PRA/PRB ratio and ligand status on metastatic evolution, in the contexts of transcriptional regulation as well as non-genomic events. We suggest the possibility to target mammary tumors by PR-selective antagonists and/or inhibitors of MAPK and FAK signalings.

Das triple-negative Mammakarzinom exprimiert weder Östrogen- noch Progesteronrezeptoren und es kommt zu keiner Überexprimierung des HER2-neu Gens. Daher haben bei diesem Subtyp des Mammakarzinoms spezifische Therapien, welche gezielt an diesen Rezeptoren wirken, keinerlei Nutzen. Etwa 60% aller Mammakarzinome exprimieren GnRH-Rezeptoren, welche als Ziel genutzt werden könnten. Der GnRH-Rezeptor kann für eine gezielte Chemotherapie mit zytotoxischen GnRH-Agonisten wie AN-152, bei welchem Doxorubicin an [D-Lys6]GnRH gebunden ist, genutzt werden. In der vorliegenden Arbeit habe ich in vitro als auch in vivo analysiert ob der zytotoxische GnRH-Agonist AN-152 Apoptose in triple-negativen Mammakarzinomzellen, welche GnRH-Rezeptoren exprimieren, induziert. Die GnRH-Rezeptorexpression in Tumorbiopsien triple-negativer Mammakarzinome wurde immunhistochemisch getestet. Die Zellproliferation wurde unter Verwendung des AlamarBlue®-Proliferationsassays analysiert. Die Apoptoseinduktion wurde durch die Bestimmung des mitochondrialen Membranpotentialverlustes quantifiziert. Die in vivo Experimente wurden mit Nackmäusen nach Xenotransplantation von humanen Brustkrebszellen durchgeführt. Wir konnten zeigen das die Behandlung triple-negativer aber GnRH-positiver MDA¬ MB 231, HCC 1806 und HCC 1937 Mammakarzinomzellen mit AN-152 in vitro zum apoptotischen Zelltod durch Aktivierung der Caspase-3 führt. Diese Antitumoreffekte konnten im Nacktmausmodell bestätigt werden. AN-152 inhibierte das Wachstum triple-negativer Mammakarzinomxenotransplantate in den Nacktmäusen komplett, ohne offensichtliche Nebenwirkungen. Der zytotoxische GnRH-Agonist AN-152 scheint ein passendes Medikament mit niedriger Toxizität für eine effiziente Therapie des triple-negativen Mammakarzinoms zu sein. (Föst C, Duwe F, Hellriegel M, Schweyer S, Emons G, Gründker C (2011). Targeted chemotherapy for triple-negative breast cancers via LHRH receptor. Oncol Rep, 25, 1481-7.)