Markan Jesus Research Articles

Violence and apocalyptic notions in Mark 13

Mark 13 is famously known as the most challenging text in the entire Markan gospel. In Mark 13:7–8, the Markan Jesus foretells a tumultuous period marked by wars, rumours of wars, nations in conflict and natural hazards, aligning with common motifs in apocalyptic literature. The language vividly depicts a world in upheaval, emphasising cosmic and earthly disturbances as harbingers of climactic historical moments. The destruction of the temple, announced in Mark 13:2, is subject to both literal and symbolic interpretations, with some associating it with the historical event of the Second Temple’s destruction in 70 CE and others perceiving it as a symbol of the end of an age. Approaching Mark 13 without being triggered by violent connotations is unthinkable. Hence, responsible interpretation is pivotal in addressing such potentially violent connotations, particularly considering contemporary world conflicts. Sensitivity, without compromising the truth of the message of Mark 13, is crucial when considering the text’s impact on war-torn communities. This applies both to a reading that simulates the possible intention of the text within the context in which the Gospel, according to Mark, originated and to a historically informed use of such a reading considering contemporary conflicts. This study aims to employ a historiographical hermeneutic as an investigative tool to contribute a plausible understanding of the present text and avoid utilising this text as proof to promote violence and wars today. Especially, when one considers the recent catastrophes: natural hazards, civil unrest and wars across the world. Some are quick to utilise the Olivet discourse to explain such gruesome activities.Contribution: This study contextualizes Mark 13 within the 1st century CE, focusing on the Second Temple’s destruction in 70 CE. It promotes a sensitive interpretation, avoiding justifications for contemporary violence, and highlights the text’s relevance by drawing parallels between its turmoil and current global conflicts, encouraging ethical reflection.

Jesus vs Seth-Typhon: An Audience-Critical Approach to Mark 4:35–5:20

Abstract Scholars have approached the Gerasene Demoniac pericope (Mark 5:1–20; = GDP) in light of various traditions, such as the Homeric parallels, the Watcher (i.e. Enochic) story, the scapegoat motif, and imperial-critical and gendered perspectives. Without denying the validity of these attempts, I suggest that there is still an important—but largely ignored—set of traditions that deserves our attention: the Seth-Typhon traditions. Based on an audience-critical perspective, this article suggests that several elements in GDP could allude to the Seth-Typhon traditions in the minds of the Greco-Roman audience of Mark. The strength of this method is twofold. First, it accounts for the close relationship between GDP and its preceding pericope (i.e. the Storm-Stilling pericope; Mark 4:35–41). Second, it coherently explains multiple critical motifs—the crossing of the sea, the sleeping Jesus, the attempt to drown Jesus, the sea-storm, the foreign area, the legion of demons, and the death of the pigs—featured in Mark 4:35–5:20. According to this approach, Jesus in Mark 4:35–5:20 can be read as a divine warrior who outshines his pagan counterparts (i.e. Zeus and Osiris) as he battles against the cosmic forces of evil and eventually conquers them.

Guidance from Unexpected Places after COVID-19: Learning from Jesus and the Early Christian Communities in Responding to Trauma

The COVID-19 pandemic proved challenging and traumatic for many, with its effects still being felt four years later. This article contends that the witness of Jesus of Nazareth and the early Christian communities can serve as guides for navigating post-pandemic life. This article will do so by examining the historical context of first-century Jewish Palestine with attention given to the Roman Empire’s brutality and traumatizing impact. It will then provide an analysis of the Matthean Jesus’ call to love one’s enemies and the Markan Jesus’ emphasis on bearing the cross as constructive responses to the trauma Matthew and Mark’s communities went through. Lastly, it will show how Jesus and the early Christian communities reveal that pain and trauma can be healthily transcended for better ways and behaviors. Thus, what has happened to us, however painful, can bear the seeds of a healthy purpose and meaning that can lead to us and our world becoming more humanized. The research methodology in this article is interdisciplinary, employing biblical theological, historical, and psychological methodologies.

The ‘brown envelope syndrome’: Culture of bribery and ethics at the crossroads

This article unravels the destructive practice of bribery, which is ingrained in South African culture. Through the scenarios in the public transport industry and literature review, the article reveals that indeed bribery is a reality to reckon with. It is observed in all tiers of society such as politics, businesses and religious circles. Bribery explained as a ‘brown envelope syndrome’ is rife in the South African socio-political landscape. The objective of this article is to enlighten the readers that bribery from socio-theological perspectives is ethically unacceptable. It promotes corrupt political accountability, economic inequality, social disrespect and religious hypocrisy. The article starts with personal scenarios and then delves into the definition of bribery as payment in a form of money, favours or gifts, to influence a decision, to receive favours in turn, facilitate fast delivery of goods, gain an unfair advantage, avoid legal prosecution or to supply substandard products or services. The second part of the artilce discusses how bribery clashes with Christian ethics as pointed by Jesus in Mark 7:21–22, as bribery lies buried in human hearts and manifests itself in different sins. There is a clear biblical condemnation of bribery as detestable, and that by all means possible, it should be proscribed. Bribery in political circles is known as ‘brown envelope’, which means the currency exchanges between the corrupt and the corrupted. Solutions suggested is that citizens in their national democracies should break out of the shell and become vocal against bribery. The church should emerge behind the trees and come up with prophetic discernment, wisdom and be vocal against bribery. Personally, those exposed to bribery situations must maintain wisdom and learn how to refuse offers without endangering themselves. This research unravels bribery and its devastating effects of promoting corrupt political accountability, economic inequality, social disrespect and religious hypocrisy.Contribution: This article calls for communities and churches to be vocal against bribery and encourages personal accountability when confronted with bribery offers.

Abstract B077: Subtype-specific signaling dynamics during treatment in non-responding breast cancer patients in the neoadjuvant I-SPY2 TRIAL: are there clues on how to overcome resistance?

Abstract Background: Despite ever-improving treatments (Tx) for early-stage aggressive breast cancer – e.g., neoadjuvant platinum and immune agents (IO) for TN and dual-anti-HER2 for HER2+ - many patients don’t respond, and insight into resistance mechanisms and how to overcome them are lacking. To look for clues, we performed serial gene expression profiling of non-responding patients to assess which tumor features change during treatment, and to identify dynamics most associated with distant recurrence. Methods: Non-response was defined as moderate or extensive residual cancer burden after Tx. 167 non-responders [76 HR+HER2-, 72 TN, 19 HER2+] with mRNA at one or more on-treatment time points (148 pretreatment (T0), 122 on-treatment (T1), and 120 surgical (T3)) were considered. Normalized data were scored for 112 published signatures representing immune, proliferation, ER/PR, HER2-related, ECM, and development; and for 50 Cancer Hallmarks (MSigDB). Signatures were assessed for early (T1-T0), late (T3-T1) and overall (T3-T0) changes during Tx using Wilcoxon tests, adjusted using the Benjamini-Hochberg method (BH p<0.05). 110/167 (66%) pts have distant recurrence free survival (DRFS) data, with median follow-up of ~4.5yr. Associations with DRFS were assessed using Cox Proportional Hazards modeling, also adjusted (BH log rank test p<0.05). Results: Signaling dynamics during Tx differed by receptor subtype. Within HR+HER2-, in addition to a decrease in ESR1_PGR, early decreases in proliferation and interferon (but not T/B-cell) signatures were observed; along with late increases in TGFB, IL8 and IL2, and Mast-cell. In TN, late decreases in T/B-cell, and Tumor-Immune signaling were observed, including those predicting IO sensitivity (STAT1_sig, DendriticCell and Chemokine12). Among the few signaling changes in common between subtypes were early increases in xenobiotic metabolism and late increases in hypoxia. Associations with DRFS were subtype-specific as well. In HR+HER2-, high levels of proliferation at T3 associate with decreased DRFS, and late increases in macrophage and Th1-related immune signatures associated with improved DRFS. Paradoxically, though high Mast-cell at T0 were previously shown to associate with non-pCR, high levels at T3 and increases late in Tx associate with improved DRFS. In TN, there were few significant associations with DRFS. Finally, we assessed the overlap between signatures that change during treatment and those that associate with DRFS, and to our surprise found no significant association. Conclusion: We observed subtype-specific changes in signatures over Tx in non-responders, however these changes do not generally predict an association with DRFS. Early targeting of xenobiosis; or TGFB, IL2 or IL8 in HR+HER2-, may be promising for overcoming resistance; but likely not a Mast-cell inhibitor, where high levels predict both resistance and survival. Citation Format: Denise M. Wolf, Christina Yau, Mark Jesus M. Magbanua, Rosalyn Sayaman, Julia Wulfkhule, Rosa I. Gallagher, Lamorna Brown-Swigart, Michael J. Campbell, Amrita Basu, Gillian L. Hirst, Jane Perlmutter, Angela DeMichele, Doug Yee, Lajos Pusztai, Paula R. Pohlmann, Amy S. Clark, Hope S. Rugo, Emanuel F. Petricoin, Laura J. Esserman, Laura van ‘t Veer. Subtype-specific signaling dynamics during treatment in non-responding breast cancer patients in the neoadjuvant I-SPY2 TRIAL: are there clues on how to overcome resistance? [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B077.

Abstract A014: Cell-free DNA concentration as a biomarker of response and recurrence in HER-2 negative breast cancer receiving neoadjuvant chemotherapy

Abstract Purpose: Cell-free DNA (cfDNA) shed into the blood by dying cells and its subset—circulating tumor DNA (ctDNA) exclusively released by tumors—are promising non-invasive biomarkers for predicting treatment response and survival. We sought to determine the clinical significance of cfDNA concentration in comparison to that of circulating tumor DNA (ctDNA) in patients with high-risk HER2-negative breast cancer receiving neoadjuvant chemotherapy (NAC) in the I-SPY2 trial. Methods: 283 patients with early-stage breast cancer (145 hormone receptor (HR)-positive/HER2-negative and 138 triple-negative) who had ctDNA data from a previous study (Magbanua et al. Cancer Cell 2023) were included in the analysis. CfDNA concentration in plasma was measured at pretreatment, during, and after NAC before surgery. Associations of cfDNA concentration (as a continuous and dichotomous variable using the median as cutoff) with clinicopathologic variables, response, and survival were examined. In addition, ctDNA data from the same cohort using a personalized tumor-informed test was available for comparative analysis (Magbanua et al., Cancer Cell 2023). The response endpoint was residual cancer burden (RCB) after NAC. The survival endpoint was distant recurrence-free survival (DRFS). Results: There were no significant differences in cfDNA concentration between the HR-positive/HER2-negative and TNBC groups at any time point. In the TNBC group, but not in HR-positive/HER2-negative group, high pretreatment cfDNA concentration was significantly associated with larger tumors (clinical stage T3/T4, Wilcoxon p=0.023) and higher grade (grade 3, Fisher p=0.0134). TNBC patients with no residual cancer (RCB-0 or pathologic complete response) after NAC had significantly higher cfDNA concentration 3 weeks after treatment initiation than those with extensive residual cancer after NAC (RCB-III, Kruskal-Wallis adjusted p=0.034). In the HR-positive/HER2-negative group, cfDNA concentration did not associate with response to NAC, but survival analysis showed that high cfDNA shedders at pretreatment had a significantly worse DRFS than low shedders (hazard ratio 2.12, 95% confidence interval 1.05-4.60, p=0.037). However, in the TNBC group, the difference in survival between high vs. low cfDNA shedders at all time points was not statistically significant. In contrast, as previously reported, ctDNA at all time points was significantly correlated with metastatic recurrence and death in both HR-positive/HER2-negative and TNBC groups (Magbanua et al., Cancer Cell 2023). Conclusions: In TNBC, cfDNA concentration reflected tumor burden, aggressiveness, and early response to NAC. In the HR-positive/HER2-negative group, pretreatment cfDNA concentration was prognostic for DRFS. Overall, the predictive and prognostic value of cfDNA concentration was more limited than that of ctDNA. Thus, ctDNA should be the measurement of choice when planning clinical interventions. Citation Format: Mark Jesus M. Magbanua, Ziad Ahmed, Rosalyn W. Sayaman, Lamorna Brown-Swigart, Gillian L. Hirst, Christina Yau, Denise M. Wolf, Wen Li, Amy L. Delson, Jane Perlmutter, W. Fraser Symmans, Douglas Yee, Nola M. Hylton, Laura J. Esserman, Angela M. DeMichele, Hope S. Rugo, Laura J. van ’t Veer. Cell-free DNA concentration as a biomarker of response and recurrence in HER-2 negative breast cancer receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A014.

Jesus as Post-War Refugee in Pre-War Galilee. Redescribing Apocalypticism as Temporal Deterritorialization in the Gospel of Mark

Scholars agree that the Gospel of Mark was composed around the time of the Judaean War and this paper suggests that these conditions inform the Markan Jesus’ subjectivity. Mark presents Jesus as a time-displaced man from post-War Judaea who inhabited Galilee during the reign of Herod Antipas. The Markan Jesus operates with an anachronistic hindsight, allowing him to authorize practices for the Markan readers in the post-War period, whether through explicit instruction or exemplary behavior. Jesus’ status as a post-War subject residing the pre-War period legitimates their claims within post-War Jewish authenticity politics. Such redescription can help reconceive Mark’s story as part of ordinary human processes of legitimation and authorization.

An Extended Inverted Allusion to Psalm 22 in Mark 15: Reading Reversal in the Markan Passion

AbstractThe Markan Passion narrative alludes to Ps 22 (LXX Ps 21) in reverse, culminating with Jesus’ cry: ‘My God, my God, why have you forsaken me?’ (Mark 15.34; cf. Ps 22.1). I argue that this ‘extended inverted allusion’ was an admired literary technique. Through select examples of this technique in the writings of the Hebrew Bible and Greco-Roman literature, I demonstrate its various functions—it can be employed to reverse meaning, to dissociate causation or to create new narrative trajectories. Reading Mark 15 in light of the literary functions of inverted allusion reveals new interpretive possibilities. In the Septuagint, Psalm 21 suggests that the psalmist's suffering was merited because of transgressions, but the inverted allusions to this Psalm in Mark 15 reinforce that Jesus’ suffering is unmerited (cf. Mark 15.10, 14) by decoupling the suffering from the transgressions. Additionally, in LXX Ps 21, the psalmist moves from forsakenness on account of transgressions toward divine deliverance. By alluding to this Psalm in reverse, Jesus travels the psalmist's journey in reverse. Rather than move from forsakenness toward divine deliverance, Mark's Jesus moves toward forsakenness, precisely to bring about divine deliverance.

The question of Mark 13 as an apocalypse

Background: Many researchers accept that the Gospel of Mark is apocalyptic, which necessitates the need to determine whether Mark 13’s eschatological discourse represents an apocalypse.Setting: The question of whether the early church utilised an apocalyptic worldview is widely discussed in scholarly circles.Methods: The article utilises a form-critical and syntactical analysis of the text of Mark 13.Results: Mark 13 is deliberately written in a mode displaying several apocalyptic features. The text engages the present crisis situation when Roman authorities quelled Roman resistance by destroying parts of Jerusalem, including the Temple, in response to the question of whether the present crisis indicates the end of the present aeon and the introduction of a new world.Conclusion: The Markan Jesus emphasises that the current situation introduces further suffering and persecution for believers but that does not indicate the end in itself. The time of the end is unknown, even to him. The discourse hence serves anti-apocalypse to discourage believers from overheated end-time expectations of an imminent end. Christians do not know when the end is coming, but they know who they expect to return.Intradisciplinary and/or interdisciplinary implications: The research findings contribute to Old and New Testament studies into apocalypticism.

Living the Kingdom of God: The Communal and Renewing Spirituality of Jesus in Mark

Understanding spirituality as “the sense or experience of God and the way one lives in response to that experience”, Jesus’ spirituality according to Mark may be described as relational and communal, with less attention given to the interior spiritual lives of individuals in favor of a way of relating to “all nations and all people” as beloved children of God which can renew all creation. Mark shows Jesus shaped by the experience of the God of the Exodus, Isaiah, and Daniel so that when he announced that “The Kingdom of God has drawn near”, he was proclaiming the fulfillment of the promises of this God. Furthermore, Mark shows Jesus living into this fulfillment, not merely saying it. The result is his teaching and modeling a renewing way of living among his followers, which dismantles hierarchies in favor of welcome, service, justice, etc., and enables resistance to Roman oppression without violence and death. He called followers to see how powerful this renewal of God is. When Rome recognized its power and turned their violence against him, he continued on “the Way of the Lord”, trusting in resurrection and God’s life-giving power. Thus, Mark presents Jesus as demonstrating a life-filled, communal spirituality of renewal for his followers.

Abstract P5-05-05: Monitoring for response and recurrence in neoadjuvant-treated hormone receptor-positive HER2-negative breast cancer by personalized circulating tumor DNA testing

Abstract Background: The detection of circulating tumor DNA (ctDNA) may serve as an early predictor of response and recurrence. In this study, we used a tumor-informed ctDNA test to monitor clinical outcomes in patients with high-risk hormone receptor-positive HER2-negative (HR+HER2-) tumors who received neoadjuvant chemotherapy (NAC) on the I-SPY 2 trial (NCT01042379). Methods: We collected blood samples at pretreatment, during (at 3 and 12 weeks after initiation of paclitaxel-based treatment with or without an investigational drug), after NAC prior to surgery, 4 weeks after surgery, and annually until clinical diagnosis of recurrence. Cell-free DNA was isolated from plasma (N=329 samples) and ctDNA was detected using a personalized, tumor-informed multiplex polymerase chain reaction next generation sequencing-based test (SignateraTM). All patients were at high risk for recurrence by MammaPrint. The response endpoints were pathologic complete response (pCR) and residual cancer burden (RCB), and the survival endpoint was event-free survival (EFS). Results: This analysis included 66 patients with HR+HER2- breast cancer who had blood samples collected before, during, after NAC and had at least one blood sample after surgery with sufficient plasma for analysis. 57.1% (32/56) had grade III disease; 72.4% (42/58) were node-positive; 36.2% (21/58) had T3/T4 disease; and 33.3% (22/66) were MammaPrint High 2. The percent ctDNA positivity rates at pretreatment, after NAC prior to surgery, and 4 weeks after surgery were 79.7% (47/59), 6.5% (4/62), and 2% (1/50), respectively. Significantly higher ctDNA positivity rates at pretreatment were observed in patients with larger tumors (95% in T3/T4 vs. 69% in T1/T2, Fisher’s exact p=0.0387), higher grade tumors (94% in Grade III vs. 67% in Grade I/II, p=0.0147) and by MammaPrint score (100% in High 2 vs. 71% in High 1, p=0.0052). In this high-risk HR+/HER2- cohort, 10/66 (15.2%) achieved pCR/RCB 0, who were all ctDNA-negative at surgery. 56/66 (84.8%) had no-PCR, with RCB I (limited residual cancer), II (moderate) and III (extensive) in 7 (10.6%), 31 (47.0%) and 18 (27.3%), respectively. ctDNA-positivity after paclitaxel-based treatment was significantly associated with RCB II/III status (Fisher’s exact p=0.01). All patients in this cohort with persistent ctDNA subsequently had RCB II or III at surgery. 47 patients had paired samples collected after NAC prior to surgery and at 4 weeks after surgery. Of the 47, 91.5% (43/47) were ctDNA-negative at both time points and 8.5% (4/47) were discordant; 1 was ctDNA-negative and later tested ctDNA-positive, while 3 were ctDNA-positive and later tested ctDNA-negative. 61/66 patients had EFS data with a median of 1.6 years of follow up (range: 0.6 to 5.6). 5 tested ctDNA-positive in at least one time point after surgery. Of these, 2 experienced a recurrence (one local relapse and one distant metastasis) and both tested positive at the time of recurrence. For the patient who developed a distant recurrence it was the only blood sample available at a follow-up time point; for the patient who developed a local recurrence, blood from two earlier follow-up time points had tested negative. To date, no recurrences have been observed in those whose test(s) after surgery were negative for ctDNA. Conclusions: The persistence of ctDNA during neoadjuvant therapy is associated with the extent of residual disease in a cohort of patients with HR+HER2- breast cancer in the I-SPY 2 trial and thus may be useful in identifying patients who are not having an optimal response to therapy. I-SPY 2.2 will test whether ctDNA has utility in redirecting therapy to improve surgical outcome and subsequent prognosis. Citation Format: Mark Jesus M. Magbanua, Hope Rugo, Lamorna A. Brown Swigart, Ziad Ahmed, Gillian L. Hirst, Denise M. Wolf, Ruixiao Lu, Ekaterina Kalashnikova, Derrick Renner, Angel Rodriguez, Minetta C. Liu, Christina Yau, Laura J. Esserman, Laura Van ’t Veer, Angela DeMichele. Monitoring for response and recurrence in neoadjuvant-treated hormone receptor-positive HER2-negative breast cancer by personalized circulating tumor DNA testing [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-05-05.

Abstract PD5-04: PD5-04 Characterizing the HER2-/Immune-/DNA repair (DRD-) response predictive breast cancer subtype: the hunt for new protein targets in a high-needs population with low response to all I-SPY2 agents

Abstract Background: In previous work we leveraged the I-SPY2 trial to create treatment response predictive subtypes (RPS) incorporating tumor biology beyond clinical HR/HER2, to better predict drug responses in an expanded treatment landscape that includes platinum agents, dual HER2-targeting regimens and immunotherapy [1]. We showed that best performing schemas incorporate Immune, DRD and HER2/Luminal phenotypes, and that treatment allocation based on these would increase the overall pCR rate to 63% from 51% using HR/HER2-based treatment selection. The RPS schema has been selected for prospective evaluation in I-SPY2. Using the RPS, one would prioritize platinum-based therapy for HER2-/Immune-/DRD+, immunotherapy for HER2-/Immune+, and dual-anti-HER2 for HER2+ that are not luminal. HER2+/Luminal patients have low response rates to dual-anti-HER2 therapy but may respond better to anti-AKT. However, there is still a considerable ‘biomarker-negative’ group of resistant cancers (HER2-/Immune-/DRD-) with very low pCR rates to all tested agents, that require a new therapeutic approach. Here we characterize the protein signaling architecture of these tumors to identify new target candidates. Methods: 987 I-SPY 2 patients from 10 arms of the trial were considered for this analysis. All have gene expression, pCR and RPS; 944 have distant recurrence free survival (DRFS) data; and 736 have reverse phase protein array (RPPA) data from laser capture microdissected tumor epithelium. These data – known collectively as the I-SPY2-990 mRNA/RPPA Data Resource - were recently made public on NCBI’s Gene Expression Omnibus [GEO: GSE196096]. We focus on HER2-/Immune-/DRD- tumors, applying Wilcoxon and t-tests to identify phosphoproteins that differ between HR+HER2-/Immune-/DRD- and other HR+HER2- tumors; and between TN/Immune-/DRD- and other TNs. The Benjamini-Hochberg (BH) method is used to adjust p-values for multiple hypothesis testing. In addition, the Kaplan-Meier method is used to estimate DRFS. Results: 201/736 I-SPY 2 patients with RPPA data are classified HER2-/Immune-/DRD- (HR+HER2-: n=138; TN: n=63). Of these, 8.5% (17/201) achieved pCR. Non-responding HER2-/Immune-DRD- had worse outcomes than responders (~75% vs. ~95% DRFS at 5 years). 60/139 phospho-proteins differ significantly between HR+HER2-/Immune-/DRD- and other HR+HER2- tumors (n=122). These tumors are relatively ‘cold’, in that 90% (54/60) of the phosphoprotein activities characterizing this group are at lower levels than in the overall HR+HER2- population; including immune (e.g. pPDL1, pJAK/STAT) and proliferation (e.g., Ki67, CyclinB1, pAURK) endpoints. Phosphoproteins showing higher levels in this subset include ERBB2 (BH p=1.7E-06), Cyclin D1 (BH p=1.4E-05), pAR (BH p=1.4E-05), and ER (BH p=3E-04). Within the TN subset, only 3/139 phospho-proteins differed significantly between TN/Immune-/DRD- and other TN tumors (n=189). These were all immune-related (pPDL1, pSTAT1, and HLA DR), with lower expression in the TN/Immune-/DRD- group. Conclusion: HR+HER2- and TN patients who are Immune-Low and DRD-Low have very low pCR rates to all tested therapeutics in I-SPY2 including standard chemotherapy, platinum, and immunotherapy. Senolytics (possibly targeting Cyclin D1), HER2low agents, and AR modulators may overcome resistance in HR+HER2-/Immune-/DRD-, whereas an immune activator beyond checkpoint inhibition is suggested for TN/Immune-/DRD- patients. [1] Wolf et. al., Redefining Breast Cancer Subtypes to Guide Treatment Prioritization and Maximize Response: Predictive Biomarkers across 10 Cancer Therapies. Cancer Cell 2022 Citation Format: Denise M. Wolf, Christina Yau, Julia Wulfkuhle, Rosa I. Gallagher, Lamorna A. Brown Swigart, Gillian L. Hirst, Jean-Philippe Coppe, Mark Jesus M. Magbanua, Rosalyn Sayaman, I-SPY2 Investigators, Laura Sit, Nola M. Hylton, Angela DeMichele, Donald A. Berry, Lajos Pusztai, Douglas Yee, Laura J. Esserman, Emanuel F. Petricoin, Laura Van ’t Veer. PD5-04 Characterizing the HER2-/Immune-/DNA repair (DRD-) response predictive breast cancer subtype: the hunt for new protein targets in a high-needs population with low response to all I-SPY2 agents [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD5-04.

Sleeping soul: A concept representation of metaphysical anthropology of the funeral traditions of Torajan people

The funeral tradition of the Torajan people is one of the most recognised funeral traditions in the world, a part of Indonesia’s rich indigenous knowledge. However, this particular tradition has been in decline over time because of the alienation caused by the spreading of Christianity. This research aimed to reinterpret metaphysical anthropology of the funeral tradition of the Torajan people using the concept of the sleeping soul from the narration of Jesus in Mark 5:35–42 and Daniel 12:1–3. The research used a qualitative approach with theological and ethnographic research types. The results of this study reveal that the concept of the sleeping soul in the biblical view can reinterpret metaphysical anthropology in the funeral tradition of the Torajan people as follows: (1) souls are eternal in the process of death, (2) souls of the deceased are helpless and (3) the sleeping soul is an eschatological hope for Christianity and Torajan people.Contribution: The aim of this research is to find a Christian metaphysical anthropology doctrine that is cordial to the funeral tradition of the Torajan people. The relationship between the two is that they have the same way of appreciating human existence metaphysically. This finding contributes to Christianity in the preservation of Torajan culture.

The Book of Torture: The Gospel of Mark, Crucifixion, and Trauma

AbstractLiterary analysis of texts dealing with the experiences of tortured bodies faces numerous riddles. For example, the urge to be faithful to the victims’ experience hits a wall because of language’s inadequacy to express torment. Another riddle is the urgency to represent the tortured body outside the logic of torture embodied by the torturer. By incorporating some of Elaine Scarry’s insights in The Body in Pain (1988) and paying close attention to the testimonies of those who have survived torture, this article argues that the crucifixion of Jesus in Mark 15 is a case of torture that expands beyond the crucifixion itself and bleeds into other literary topics such as discipleship and the temple.

Abstract P2-01-03: Elucidating the biology of circulating tumor DNA (ctDNA) shedding across receptor subtypes in high-risk early-stage breast cancer

Abstract Background: Identifying mechanisms that govern the shedding of ctDNA in blood could inform the use of liquid biopsy in individual patients. Previous studies in the I-SPY2 neoadjuvant trial involving high-risk breast cancer showed that the detection of ctDNA before treatment was associated with aggressive clinical characteristics and residual ctDNA after treatment was associated with poor outcomes. Moreover, ctDNA positivity rates significantly varied across breast cancer subtypes suggesting that ctDNA shedding may in part be driven by subtype-specific etiology. We performed genome-wide transcriptomic analysis to identify genes and biological processes associated with increased ctDNA shedding within and across receptor subtypes. Methods: Our study involved 227 patients in I-SPY2 with tumor gene expression and ctDNA data at pretreatment. All patients were at high risk for recurrence (MammaPrint high). Each subtype: HR+HER2- (n=109), HER2+ (n=19), and triple negative breast cancer (TNBC, n=99) was evaluated independently. We performed differential expression (DE) analysis on the global transcriptome (m=19,134 genes) and curated gene signature (cGS, m=31 signatures developed in I-SPY2) data between ctDNA+ and ctDNA- patients at baseline. Gene-set enrichment analysis (GSEA) was also performed across hallmark (H, m=50), canonical pathway (CP, m=5,501), gene ontology (GO, m=9,996) and immunologic (IM, m=4,872) gene sets. Features were associated with ctDNA shedding if Benjamini-Hochberg adjusted p < 0.05. For subtypes with smaller sample size and unbalanced groups, we also report features with nominally significant p < 0.05. Results: ctDNA positivity rate was significantly higher in TNBC (91%) than in HR+HER2- and HER2+ (65% and 74% respectively, Fisher p <0.001). The HR+HER2- subtype had the most significant hits for DE analysis between ctDNA+ and ctDNA- patients, with 0.2% of genes and 3.2% of cGS. No genes or cGS were differentially expressed in TNBC and HER2+, likely due to imbalance or small size of these groups. For GSEA, we observed the most significant number of enrichments in HR+HER2- subtype, with 58%, 21.8%, 4.4% and 40.3% of H, CP, GO, and IM gene sets enriched, respectively. In the HER2+ subtype, 40% H, 15.7% CP and 36.4% IM gene sets were significantly enriched, while no gene sets were enriched in TNBC. To identify common mechanistic themes across subtypes, we also considered nominally significant features in DE and GSEA. Processes associated with infection and innate immune responses were enriched in ctDNA+ patients, while adaptive immune response and antigen presentation—e.g., T-cell, TCR and MHC II protein complex, and downregulation of MYC targets were enriched in ctDNA- patients. HR+HER2- and HER2+ subtypes shared the most common modulated features with 134 genes and 2,165 gene sets, including up-regulation of cell cycle and proliferation in ctDNA+ patients, as well as up- or down-regulation of specific immunologic and metabolic processes. In contrast, TNBC gene set enrichment was associated with more distinct biologic processes, sharing common enrichment of 113 and 27 gene sets with HR+HER2- and HER2+ subtype, respectively. Conclusions: Findings from our exploratory analysis suggest a key role of immune response pathways in the control of ctDNA release. Additionally, tumor cell proliferation was associated with increased shedding in HR+HER2- and HER2+ subtypes, while down regulation of MYC targets was associated with ctDNA- patients across all subtypes. These suggest an important role of cell cycle in ctDNA shedding. Overall, our analysis revealed common and unique mechanisms potentially associated with ctDNA shedding across and within subtypes. However, due to the unbalanced groups and limited sample sizes, validation in a larger cohort is warranted. Citation Format: Rosalyn W. Sayaman, Denise M. Wolf, Christina Yau, Lamorna Brown Swigart, Gillian L. Hirst, Laura Sit, Nicholas O'Grady, Amy L. Delson, I-SPY2 Investigators, Laura Esserman, Laura J. van 't Veer, Mark Jesus M. Magbanua. Elucidating the biology of circulating tumor DNA (ctDNA) shedding across receptor subtypes in high-risk early-stage breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-01-03.

Eve-Marie Becker, Helen Bond, and Catrin Williams, eds. John’s Transformation of Mark.

Eve-Marie Becker, Helen Bond, and Catrin Williams, eds. <i>John’s Transformation of Mark.</i>

Mark, a Pauline Theologian: A Re-reading of the Traditions of Jesus in the Light of Paul’s Theology.

Mark, a Pauline Theologian: A Re-reading of the Traditions of Jesus in the Light of Paul’s Theology.

Missio hominum as the compassionate response to socio-economic and vaccine challenges during COVID-19 in South Africa

It is likely that the storm of coronavirus disease 2019 (COVID-19) in South Africa will calm only when the country attains herd immunity. In South Africa, the COVID-19 vaccine roll-out plan will first prioritise key frontline forces, the elderly and those with comorbidities. Although there is some new academic insight on COVID-19 within the context of churches, not much has been written on the role that churches can play in partnership with government towards procuring vaccines for the poor people of South Africa. The contribution towards vaccine procurement by churches is juxtaposed with the proclamation of the year of the Lord’s favour in Luke 4:18–19 and the feeding of 5000 men (excluding women and children) in Matthew 14:13–21, Mark 6:30–44, John 6:1–14 and Luke 9:10–17. This is done against an environment where corruption in the procurement of personal protective equipment, unjust food parcel distribution and subverted relief packages occurred during the hard lockdown of 2020. This article makes use of both missio Dei and missio hominum as its missiological theory in conformity with calls for public health restoration during and after COVID-19. It employs a literature review to support missio Dei and missio hominum as compassion and fundraising for the poor in the face of COVID-19, as exemplified by Paul in 1 Corinthians 16:1–4 and Jesus in Mark 6:8 and Luke 8:1–3.Contribution: In order to preserve lives that would otherwise be lost whilst waiting for the COVID-19 vaccine, this article entreats all churches of South Africa to launch a nationwide church fundraising effort towards procuring COVID-19 vaccines for the poor following the example of the Solidarity Fund, which was established by President Cyril Ramaphosa as one of the early interventions to cushion the impact of COVID-19.

The Markan Proskuneo (Mark 5:6; 15:19) as Anti-Roman Motif in Mark’s Gospel

The Roman provenance of the Gospel according to Mark is not in doubt, and the reapplication of some concepts reserved for the Roman emperor to the person of Jesus in Mark’s Gospel is well documented. The article considers that the act of proskuneo, rendered to the Roman emperor as a divine being during the time of the writing of Mark’s Gospel, has been applied by Mark to serve an anti-Roman program. The passages where the Gerasene demoniac prostrates before Jesus (Mark 5:6) and where the Roman soldiers make a mock reverence to Jesus (Mark 15:19) are considered from both exegetical and historical perspectives.

Abstract PS2-07: Outcomes associated with disseminated tumor cells at surgery after neoadjuvant chemotherapy in high-risk early stage breast cancer: The I-SPY SURMOUNT study

Abstract Background: Disseminated tumor cells (DTCs) in bone marrow detected after treatment may represent occult residual disease. We enumerated DTCs after neoadjuvant chemotherapy (NACT) in patients (pts) diagnosed with high-risk early stage breast cancer and examined the relationship of these cells with response and survival. Methods: I-SPY SURMOUNT is a sub-study of the I-SPY 2 TRIAL (NCT01042379). Pts enrolled on I-SPY 2, who signed consent for this sub-study, had bone marrow aspirates (BMA) collected after NACT at the time of surgery. DTCs were isolated and enumerated from BMA using immunomagnetic enrichment/flow cytometry (IE/FC). DTCs were defined as EPCAM-positive and CD45-negative nucleated cells. Samples were considered positive using a predetermined threshold of &amp;gt;4 DTCs per mL (Magbanua et al, unpublished data). Pathologic response was assessed using the residual cancer burden (RCB) method at local sites, and pts underwent standard adjuvant therapy if indicated and follow up for recurrence events and death. Relationship of DTCs with clinicopathologic variables was examined using Chi-squared test. Group means were compared using t tests. The log-rank test was used to compare survival curves. Results: A total of 73 patients were enrolled, 51 of whom had successful DTC assessment. The median DTC per mL was 4 (interquartile range 1.2-11.6). 24/51 (47%) were DTC-positive. Clinical characteristics by DTC status are shown in the table. DTC-positive pts were significantly younger (p=0.02) and had larger pretreatment tumors (longest diameter by magnetic resonance imaging) compared to DTC-negative pts (p=0.032). DTCs were not associated with receptor subtype. Thirty pts (41%) achieved a pathologic complete response (pCR). DTCs were not associated with pCR (p= 0.166); however, DTC-positive patients were significantly more likely to have residual cancer (RCB-II/III) after NACT compared to DTC-negative patients (OR 3.3, p=0.037). Median follow up of this cohort was 2.8 years (range: 0.9-4.8). Interim survival analysis showed that DTCs were not significantly correlated with EFS (p=0.6) or DRFS (p=0.41). Conclusions: Detection of DTCs at surgery after NACT is significantly more common in young patients, those with larger tumors, and those with residual disease at surgery. While these associations suggest higher risk for later recurrence, larger studies and longer follow up are necessary to determine if DTCs add prognostic value over pathologic evaluation alone for pts receiving NACT. Citation Format: Mark Jesus M Magbanua, Laura van 't Veer, Amy Clark, A. Jo Chien, Judy Boughey, Heather Han, Anne Wallace, Heather Beckwith, Minetta Liu, Christina Yau, E. Paul Wileyto, Lamorna Brown Swigart, Jane Perlmutter, Lauren Bayne, Shannon Deluca, Stephanie Yee, Erica Carpenter, Laura Esserman, John Park, Lewis Chodosh, Angela DeMichele. Outcomes associated with disseminated tumor cells at surgery after neoadjuvant chemotherapy in high-risk early stage breast cancer: The I-SPY SURMOUNT study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-07.