bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B018: GSK3β inhibition synergizes with radiation therapy to stimulate type-I interferon and anti-tumor effects in lung cancer
Authors: Braun Chen , Li Nan , Lin Steven H. 
Published: January 2025

Abstract
Radiation therapy (RT) is widely used to treat various tumor types to minimize the risk of recurrence. However, only a subset of patients experiences significant responses to RT, primarily due to inadequate immune responses within lung tumors. Therefore, there is a pressing need to develop innovative strategies to overcome tumor immunosuppression following RT. In this study, we investigated alternative mediators that could mitigate the effects of immunosuppression in lung cancer cells. We screened over 700 pharmacological inhibitors using an interferon beta-1(IFNβ1)-luciferase reporter system, identifying a group of glycogen synthase kinase 3 beta inhibitors (GSK3βi) that enhanced IFNβ1 expression. Notably, one GSK3βi agent, Kenpaullone, significantly induced IFNβ1 in multiple lung cancer cell lines. Compared to other GSK3β inhibitors, it exhibited superior synergy (over 20-fold) without inducing cellular cytotoxicity, even at high doses (30 µM). Furthermore, our syngeneic mouse models showed that GSK3βi and RT reduced tumor size more effectively than monotherapy and enhanced immunologic response in these tumors. This pharmacological-RT combination approach holds promise for improving the immunologic response to RT in lung cancer patients, potentially reducing tumor burden in those that already exhausted standard of care treatment options.
Citation Format: Chen Braun Nan Li, Steven H. Lin. GSK3β inhibition synergizes with radiation therapy to stimulate type-I interferon and anti-tumor effects in lung cancer. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B018
Abstract B032: Concurrent mutant KRAS inhibition and Stereotactic Body Radiation Therapy (SBRT) for preclinical KRASG12D-Driven Pancreatic Ductal Adenocarcinoma (PDAC) treatment
Authors: Wang Tianyu , Chen Jasper R , Pagan Vincent Bernard , Wang Liang , Guo Youming , Xia Ling , Singh Pankaj K. , Jiang Dadi , Koong Albert 
Published: January 2025

Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is known for its extensive intrinsic and acquired resistance to standard of care therapies. With the KRASG12D mutation being a key driver, MRTX1133, a selective small molecule KRASG12D inhibitor, has demonstrated superior anti-tumor efficacy in preclinical PDAC models. However, tumor resistance to MRTX1133 is expected to occur inevitably. We hypothesize that combining MRTX1133 with stereotactic body radiation therapy (SBRT) can enhance local tumor control and minimize tumor recurrence after treatment. Methods: C57Bl/6J mice orthotopically transplanted with luciferase-tagged mouse KPC PDAC cells (KrasG12D; Trp53R172H; Pdx1-Cre) were assigned to 4 treatment groups: (1) vehicle, (2) SBRT (8 Gy x 5), (3) MRTX1133 (30 mg/kg I.P. BID), and (4) SBRT + MRTX1133. Tumor progression was monitored with IVIS luciferase imaging, and survival data were collected and analyzed using a Log-rank test. At the study endpoint, tumors as well as normal tissues were collected for histological analysis to evaluate immune cell infiltration, tumor proliferation and differentiation, and normal tissue toxicity. Results: SBRT + MRTX1133 combination therapy significantly enhanced local tumor control and prolonged mouse survival when compared to either MRTX1133 or SBRT alone. The median survival in the combination group exceeded 120 days, with significantly reduced tumor burden, suggesting a synergistic effect between SBRT and MRTX1133 in suppressing KPC tumor progress in vivo. Conclusion: Our findings demonstrate that MRTX1133 combined with SBRT improves tumor control and overall survival in a preclinical KRASG12D-driven PDAC tumor model. This combination strategy has the potential for clinical translation, offering a promising therapeutic approach to overcome resistance and improve outcomes in PDAC patients.
Citation Format: Tianyu Wang, Jasper R Chen, Vincent Bernard Pagan, Liang Wang, Youming Guo, Ling Xia, Pankaj K. Singh, Dadi Jiang, Albert Koong. Concurrent mutant KRAS inhibition and Stereotactic Body Radiation Therapy (SBRT) for preclinical KRASG12D-Driven Pancreatic Ductal Adenocarcinoma (PDAC) treatment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B032.
Abstract B033: Long-Term quality of life and hearing preservation after stereotactic radiosurgery for vestibular schwannoma
Authors: Siddiqui Shayzal , Lee Joseph S. , Abbo Julia , Cummings Jessica , Desai Avi , Grills Inga S. , Chen Peter Y. , Jacob Jeffrey , Lee Kuei C. 
Published: January 2025

Abstract
Purpose/Objective(s): The aim of this study is to evaluate the long-term quality of life (QOL) and hearing preservation outcomes following definitive single-fraction Gamma Knife stereotactic radiosurgery (GKSRS) for vestibular schwannoma (VS). Materials/Methods: Baseline and follow-up QOL and audiogram data were collected from our prospectively maintained institutional database of VS patients treated with single-fraction GKSRS from 2006 to 2023. QOL metrics included the Hearing Handicap Inventory (HHI), Dizziness Handicap Inventory (DHI), Tinnitus Handicap Inventory (THI), and the 36-Item Short-Form Survey (SF-36). Serviceable hearing preservation was classified according to the Gardner-Robertson scale using pure-tone average (PTA) and speech discrimination (SD). Linear mixed-effects models were constructed for each QOL metric over time. Results: A total of 388 patients (median age 61 years) were included with a median follow-up of 48 months. Median tumor size was 1.6 cm (interquartile range [IQR] 1.1-2.1 cm), with a median tumor volume of 0.6 cc (IQR 0.2-1.6 cc). Most patients received a prescription marginal dose of 12.5 Gy with a median cochlear mean dose of 2.7 Gy (IQR 1.9-3.8 Gy). Baseline median HHI, DHI, THI, and SF-36 scores were 28, 12, 12, and 73 respectively. Linear mixed-effects analyses indicated no statistically significant decline in any of these QOL metrics up to 7 years after GKSRS. Of patients with serviceable hearing at baseline, hearing preservation was maintained in 79% at 12 months, 67% at 2 years, and 68% at 3 years. Conclusion: GKSRS preserves long-term patient quality of life and serviceable hearing in the definitive management of VS.
Citation Format: Shayzal Siddiqui, Joseph S. Lee, Julia Abbo, Jessica Cummings, Avi Desai, Inga S. Grills, Peter Y. Chen, Jeffrey Jacob, Kuei C. Lee. Long-Term quality of life and hearing preservation after stereotactic radiosurgery for vestibular schwannoma. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B033.
Abstract IA02: Preserving tumor-draining lymph nodes in the era of immuno-oncology: Opportunities for precision chemo-radio-immunotherapy
Authors: Gutkind J. Silvio 
Published: January 2025

Abstract
The advent of the current cancer immunotherapy era based on the success of immune checkpoint blockade (ICB) inhibiting programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) has revolutionized the standard of care for cancer treatment. However, the limited response rates to ICB across multiple cancer types suggest that new approaches and treatment strategies are needed in order to achieve durable cancer remission. This includes re-examining the possibility that standard of care treatments, including surgery and chemo-radiation, may compromise the tumor response when delivered in concert with ICB. In particular, many cancer types, including head and neck squamous cell carcinoma (HNSCC), have a propensity to metastasize to locoregional lymph nodes, and standard oncologic management often involves elective ablation of tumor draining lymph nodes (tdLN). In a recent study, we have used tobacco-signature HSNCC syngeneic mouse models and showed that tdLN ablation by surgery or radiation therapy limits the tumor ICB response, thereby worsening overall survival and repolarizing the tumor- and peripheral-immune compartments. Mechanistically, we provided evidence that cDC1 dendritic cells in the tumor lesions and tdLN are required for an effective anti-tumor immune response. Recently, we have cross-integrated large single-cell RNA-sequencing datasets from intratumoral immune cells and identified a novel mechanism by which antigen-specific CD8+ T cells promote intratumoral cDC1 accumulation and T cell persistence, leading to improved overall survival. As a multipronged approach, we have also built on this computational pipeline to identify druggable oncogenic signaling networks that override cancer immune surveillance. Evidence will be presented that disruption of specific HNSCC driving signaling axes is sufficient to sculp the tumor immune microenvironment and disable their immune evasive mechanisms, thereby providing opportunities for the development of new precision therapies increasing the response ICB. The emerging information also provided a rationale for investigating the use of a new generation of radiation-sensitizing antibody drug conjugates targeting cancer-specific oncosignaling drivers, in combination with radiotherapy and ICB in the neoadjuvant setting, when tdLN are still intact. Ultimately, evidence will be presented supporting the future evaluation of spatially precise radiosensitizing antibody drug conjugate-directed chemo-radio-immunotherapy for precision cancer care in HNSCC and other malignancies.
Citation Format: J. Silvio Gutkind. Preserving tumor-draining lymph nodes in the era of immuno-oncology: Opportunities for precision chemo-radio-immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA02
Abstract IA05: Toward multi-modal foundation AI for precision oncology
Authors: Li Ruijiang 
Published: January 2025

Abstract
Clinical decision-making is a complex process that involves information obtained from multiple data modalities. Artificial intelligence (AI) approaches that can effectively integrate multi-modal data hold significant promise to advance clinical care. Two areas of success are imaging and digital pathology, where AI has shown great potential to improve cancer diagnosis and treatment. This talk will provide an overview on how AI can be used to extract information from imaging and pathology and identify prognostic and predictive biomarkers for personalized cancer treatment. In particular, I will present our recent work on building multi-modal foundation models for precision oncology.
Citation Format: Ruijiang Li. Toward multi-modal foundation AI for precision oncology. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA05
Abstract IA07: Improving CAR T cell therapy efficacy in hematologic malignancies with low-dose total body irradiation
Authors: Guzman Monica L. 
Published: January 2025

Abstract
Chimeric Antigen Receptor (CAR) T cell therapy represents a significant advance in the treatment of hematologic malignancies, as demonstrated by the high response rates and improved survival in diseases such as acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), Diffuse large cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL). The FDA has approved several CAR T cell therapies, including some approaches targeting CD19 (CART19) for adult and pediatric patients with B-cell malignancies. Response rates for CD19 CART therapy have been quite promising, reaching 80% overall response and 60% complete response; however, relapses are observed at an estimate of 30-40% within the first year. Thus, finding clinically translatable approaches to improve response rates for patients receiving CART19 therapies, such as the potential of LD-TBI, is critical. Multiple mechanisms of CAR T cell therapy resistance include limited persistence of the CAR T cell product upon infusion, CAR T cell exhaustion, and reduced or complete loss of target expression. Here, we will describe the significant role of radiation therapy, particularly low-dose total body irradiation (LD-TBI), in enhancing the long-term response of CAR T cell therapy. LD-TBI can modulate antigen stability, augment the expression of death receptors in tumor cells, and improve the persistence of CAR T cells. Moreover, LD-TBI also enhances lymphodepletion and the trafficking of CAR T cells to the tumor-infiltrated organs. As a result, LD-TBI significantly prolongs the survival of mice bearing lymphoma or B-ALL in combination with anti-CD19 CAR T cells, thereby improving patient outcomes and offering a promising future for cancer treatment.
Citation Format: Monica L. Guzman. Improving CAR T cell therapy efficacy in hematologic malignancies with low-dose total body irradiation. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA07
Abstract IA10: Immune side effects in ferroptosis-targeted therapy
Authors: Tang Daolin 
Published: January 2025

Abstract
Ferroptosis, a regulated form of cell death driven by lipid peroxidation, has emerged as a promising strategy in cancer therapy, complementing established modalities such as chemotherapy, immunotherapy, and radiotherapy. While the mechanisms of ferroptosis are highly context-dependent, the classical approach to inducing ferroptosis involves targeting the GPX4 (glutathione peroxidase 4) pathway. GPX4 is a critical enzyme that detoxifies lipid hydroperoxides (L-OOH) by reducing them to non-toxic lipid alcohols (L-OH) using glutathione (GSH) as a cofactor, thereby preventing lipid peroxidation and ferroptotic cell death. Although targeting GPX4 effectively induces ferroptosis in cancer cells, its widespread expression in both tumor and normal cells presents challenges. Direct inhibition of GPX4 can lead to unintended immune cell death, potentially impairing antitumor immunity by reducing the activity of cytotoxic T cells and other immune effectors essential for robust immune responses. This immunosuppressive effect could undermine the therapeutic benefits of ferroptosis-targeted therapies. To overcome this limitation, alternative strategies have been explored. For instance, non-direct targeting of GPX4, such as inducing TRIM25-mediated degradation of GPX4, has shown promise in selectively killing cancer cells while sparing normal tissues and preserving immune function. This approach minimizes toxicity and maintains the activity of key immune cells, including cytotoxic T cells, enhancing the overall efficacy of ferroptosis-based treatments. Understanding the potential risks and immune-related side effects of ferroptosis-targeted therapies is critical for their successful clinical translation.
Citation Format: Daolin Tang. Immune side effects in ferroptosis-targeted therapy. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA10
Aviso de incêndio: o mal-estar no laço educativo e a dimensão sociopolítica do sofrimento escolar
Authors: Fagundes Patrícia da Conceição , Gurski Rose 
Published: January 2025

This article reflects about the malaise in the educational bond and its effects on the psychological suffering of adolescents based on a research-intervention experience carried out in a school institution in the south of the country. We start from the sociopolitical dimension of the suffering of school subjects in order to constitute a clinical-political intervention strategy through the presence of psychoanalytic listening and ethics at school. We highlight the crossings of the new school order in the narratives of school subjects, in conjunction with the social inequalities that are expressed in the Brazilian educational problem, increased more currently by neoliberal practices. Inspired by the Benjaminian aphorism about the “Fire Alarm”, we open up new possibilities to listen to discomfort and psychological suffering in the space of the school institution.
Aspectos da poética de Sérgio Vaz, voz da periferia, em Flores da batalha
Authors: Lara Fernando Martins 
Published: January 2025

RESUMO: Este artigo tem por objetivo principal analisar a constituição do éthos de Sérgio Vaz em Flores da Batalha (2023), compreendendo-a dentro da trajetória editorial do poeta. Dessa forma, a análise perpassa outras obras do autor, como Colecionador de Pedras (2011), Literatura, pão e poesia (2011) e Flores de Alvenaria (2016). Além disso, a partir da abordagem comparatista, busca-se iluminar aspectos intertextuais e interdiscursivos de sua composição, que sustentam a caracterização do orador.
Economia do Cuidado e Equidade de Gênero no Trabalho:o papel das políticas públicas de assistência social e dos novos arranjos de trabalho
Authors: Duarte Andressa , Morimoto Lays Harumi 
Published: January 2025

Este trabalho busca analisar o papel da mulher na economia do cuidado e sua relação com a equidade de gênero no mercado de trabalho, contextualizando a vinculação da mulher ao trabalho reprodutivo, a luta feminista pela valorização do trabalho doméstico como um trabalho reprodutivo e fornecedor de força de trabalho dentro do sistema capitalista. A partir da apresentação de indicadores sociais e econômicos históricos e contemporâneos, conclui-se que, mesmo com a crescente participação feminina no mercado de trabalho e os novos arranjos familiares, ainda existe uma lacuna importante quanto a políticas públicas e mudanças na legislação trabalhista que corroborem para a redução das desigualdades no papel do trabalho de cuidado não remunerado, para a desvinculação do cuidado da figura feminina, de forma a desresponsabilizar a família, de forma integral e predominante, do cuidado com idosos e pessoas com deficiência, e para ampliar o amparo ao cuidado de crianças para além da gestação e primeiros meses de vida.
Contextualização Sociopolítica dos Cocos: passado, presente e futuro
Authors: Padilha Ísis Arrais , Amaral Renata Pompêo do , Pereira Sayonara Sousa 
Published: January 2025

O objetivo deste artigo é oferecer uma breve revisão histórica da relação entre os Cocos e a sociedade. Neste percurso, apresentamos a origem do gênero nomeando suas principais características, passamos por episódios de perseguição e seguimos pelo caminho da popularização da linguagem com o advento do rádio. São delineadas as principais iniciativas de pesquisa acadêmica e institucional dos cocos, apresentam-se as primeiras impressões a partir de um estudo de campo junto ao Coco de Tebei e aponta-se a necessidade de avançar para a patrimonialização dos Cocos. As conclusões reforçam a necessidade de transformas a relação entre os cocos e a sociedade por meio de ações concretas em âmbitos diversos.
A comparative study of the effect of capsular repair in the Latarjet procedure
Authors: McBride Andrew P. , Lafosse Thibault , Karanja Alex N. , Lafosse Laurent , Hughes Ian P. , Hoy Gregory A. , Ek Eugene T. , Barwood Shane A. , Taylor Fraser , Tan Ezekiel 
Published: January 2025

Abstract

Background
Long term studies have shown the Latarjet procedure to be successful in preventing re-dislocation in primary and recurrent anterior inferior shoulder instability. It provides stability through the sling effect of the conjoint tendon and the bone block. It is unclear whether augmentation with capsular repair provides an added benefit or leads to restricted range of external rotation. The primary aim of this study is to evaluate the effect of capsular repair in the open Latarjet procedure on rotational range of active external rotation in 90 degrees abduction (RoM-ER90). The secondary aim is to evaluate the effect on clinical outcomes including post-operative apprehension, instability, proprioception and shoulder function scores.

Methods
This is a multi-national retrospective cohort study including patients with a minimum of 6-months follow-up post Latarjet procedure performed between 2016 and 2020 recruited from 3 units in Australia and France. Range of motion was measured using a Proteck goniometer. Clinical outcomes were assessed using the Western Ontario Shoulder Instability Index (WOSI), Oxford shoulder, Oxford instability, Walch-Duplay and Rowe scores. Shoulder proprioception was assessed by the active relocation test described by Glendon et al.

Results
Forty-four patients were included, median age was 29.5 years and 91% male. Three groups were assessed, open latarjet with no capsular repair (OL n = 11), open latarjet with capsular repair (OLCR n = 20), and arthroscopic Latarjet without capsular repair (AL n = 13). There was no apparent effect of capsular repair on the ROM-ER 90 in the open groups with a median (interquartile range) of 78° (72°, 90°) for OL and 84° (75°, 90°; P = 0.87) for OLCR groups. Capsular repair and arthroscopic approach did not affect the proportion of patients reporting shoulder apprehension (P = 0.52 and 0.48 respectively). There was no difference in proprioception between operative and non-operative sides for the OL group (P = 0.43). Proprioception was poorer on the operative side for the OLCR group (P = 0.04) but better on the operative side for the AL group (P = 0.08). WOSI scores for the open surgical groups were similar (OL = 78, OLCR = 80, P = 0.91) and when combined (median WOSI = 79) demonstrated greater stability than the AL group (P = 0.009). There was no evidence of an effect of capsular repair or arthroscopic approach on the Walch-Duplay, Oxford Instability, or Rowe scores.

Conclusions
There is no significant difference in ROM-ER 90 or WOSI score in patients who undergo the Latarjet procedure with and without capsular repair. The arthroscopic Latarjet may preserve proprioception but did not improve shoulder stability compared to the open Latarjet.

Level of evidence
III, retrospective cohort study.