Giant cell tumor of bone (GCT) is a generally benign, osteolytic neoplasm comprising stromal cells and osteoclast-like giant cells. The osteoclastic cells, which cause bony destruction, are thought to be recruited from normal monocytic pre-osteoclasts by stromal cell expression of the ligand for receptor activator of nuclear factor kappaB (RANKL). This model forms the foundation for clinical trials in GCTs of novel cancer therapeutics targeting RANKL. Using expression profiling, we identified both osteoblast and osteoclast signatures within GCTs, including key regulators of osteoclast differentiation and function such as RANKL, a C-type lectin, osteoprotegerin, and the wnt inhibitor SFRP4. After ex vivo generation of stromal- and osteoclast-enriched cultures, we unexpectedly found that RANKL mRNA and protein were more highly expressed in osteoclasts than in stromal cells, as determined by expression profiling, flow cytometry, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. The expression patterns of molecules implicated in signaling between stromal cells and monocytic osteoclast precursors were analyzed in both primary and fractionated GCTs. Finally, using array-based comparative genomic hybridization, neither GCTs nor the derived stromal cells demonstrated significant genomic gains or losses. These data raise questions regarding the role of RANKL in GCTs that may be relevant to the development of molecularly targeted therapeutics for this disease.
Morality is one of the fundamental structures of any society, enabling complex groups to form, negotiate their internal differences and persist through time. In the first book-length study of Roman popular morality, Dr Morgan argues that we can recover much of the moral thinking of people across the Empire. Her study draws on proverbs, fables, exemplary stories and gnomic quotations, to explore how morality worked as a system for Roman society as a whole and in individual lives. She examines the range of ideas and practices and their relative importance, as well as questions of authority and the relationship with high philosophy and the ethical vocabulary of documents and inscriptions. The Roman Empire incorporated numerous overlapping groups, whose ideas varied according to social status, geography, gender and many other factors. Nevertheless it could and did hold together as an ethical community, which was a significant factor in its socio-political success.
This study argues for the recovery of trust as a central theme in Christian theology, and offers the first theology of trust in the New Testament. ‘Trust’ is the root meaning of Christian ‘faith’ (pistis, fides), and trusting in God is fundamental to Christians. But unlike faith, and other aspects of faith such as belief or hope, trust is little studied. Building on her ground-breaking study Roman Faith and Christian Faith, Teresa Morgan explores the significance of trust, trustworthiness, faithfulness, and entrustedness in New Testament writings. Trust between God, Christ, and humanity emerges as a risky, dynamic, forward-looking, life-changing partnership. God entrusts Christ with winning the trust of humanity and bringing humanity to trust in God. God and Christ trust humanity to respond to God’s initiative through trust in Christ, and entrust the faithful with diverse forms of work for humanity and for creation. Human understandings of God and Christ are limited, and trust and faithfulness often fail, but, before the end time, imperfect trust is never a deal-breaker. Morgan develops a new model of atonement, showing how trust enables humanity’s release from the power of sin and the suffering caused by sin. She examines the neglected concept of propositional trust, and argues that it plays a key part in faith. This book offers a vision of Christian trust as soteriological, ethical, and community-forming. Trust is both the means of salvation and an end in itself, because where we trust is where we most fully live.
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