bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 724: Leaving cancer patients behind for greener pastures: The clinical oncology workforce in Nigeria
Authors: Chidebe Runcie C.W. 
Published: April 2023

Abstract
Background: For a population of over 201 million, Nigeria has only 4 doctors per 10,000 patients and 16.1 nurses, midwives per 10,000 patients, and less than 100 clinical oncologists for over 100,000 cancer patients. While Nigeria has one of the worst cancer burdens in the world and workforce shortage; 9 in 10 Nigerian physicians are seeking for opportunities to leave for the USA, UK and Canada. To improve oncology care in Nigeria, it may be important to understand the push and pull factors contributing to migration of clinical oncology (CO) workforce. Mathew (2018), Vanderpuye, et al., (2019), Balogun, et al., (2017), and Adebayo, (2016) have done research on CO; however, their studies were vastly focused on the African continent and not country-specific nor focused on the CO workforce in Nigeria.
Aim: The aim of this study is to explore the push and pull factors to stay or leave clinical oncology workforce in Nigeria.
Method: Using a mixed-method research approach, 80 participants completed the questionnaire and 9 participants responded to semi-structured interview. Multiple linear regression and Grounded theory was used for the data analysis.
Results: The results show that CO workload and satisfaction were significantly related to turnover intention. The qualitative results showed that CO as a new area of specialization, mentorship, career growth and attractiveness of radiation science are pull factors. While, high CO workload, poor healthcare system, poor remuneration, corruption in the public sector, and few other themes are push factors. Empathy for patients, patriotism and sense of fulfilment unexpectedly emerged as retention factors in the study.
Conclusion: Nigeria can improve patient’s treatment outcome by the reduction of CO workload through the employment of more CO. More CO can be available for employment when they are attracted, and their training is optimized. Those employed can be retained by improving working conditions and the introduction of work benefits. Our
recommendations are that health leaders should create more CO training and awareness of CO in Nigeria.
Citation Format: Runcie C.W. Chidebe. Leaving cancer patients behind for greener pastures: The clinical oncology workforce in Nigeria [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 724.
Abstract 93: An endogenous molecular brake preventing APOBEC-driven tumor mutational burden, heterogeneity and therapy resistance
Authors: Mu Ping , Li Xiaoling , Wang Yunguan , Wang Tao , Deng Su 
Published: April 2023

Abstract
Tumor mutational burden and heterogeneity fuel resistance to many targeted therapies, which inevitably limits the clinical outcome of patients. The cytosine deaminase APOBEC proteins are major drivers of mutagenesis in human cancer, with over 70% of tumors exhibiting a mutational signature that is impacted by APOBEC activity. Nevertheless, the mechanisms through which tumor cells hijack the powerful APOBEC mutagenesis machinery to promote heterogeneity and therapy resistance remain largely unknown. Through a multi-disciplinary approach integrating bulk and single cell RNA-Seq (scRNA-Seq), whole-genome exome-sequencing (WES), and CRISPR library screening, we identified a long sought-after cell-intrinsic mechanism that prevents APOBEC-driven mutagenesis in non-malignant cells. The loss of this “molecular brake”, unleashes APOBEC3B-driven mutagenesis in malignant cells, which then becomes a key mutator and represents the long sought-after molecular source of driver mutations in some frequently mutated genes in cancers, including FOXA1, EP300, and AR. Functional screening identified eight crucial drivers for Androgen Receptor (AR)-targeted therapy resistance in prostate cancer that are mutated by APOBEC3B: BRD7, CBX8, EP300, FOXA1, HDAC5, HSF4, STAT3 and AR. Finally, contrary to conventional understanding, our study reveals that driver mutations in FOXA1 induced by APOBEC3B, not mutations in AR, evolutionarily outcompete other driver mutations and eventually dominate the resistant tumors. Collectively, these results uncover a cell-intrinsic mechanism that unleashes APOBEC-driven mutagenesis, which plays a significant role in conferring targeted therapy resistance and could be the potential therapeutic targets to overcome resistance.
Citation Format: Ping Mu, Xiaoling Li, Yunguan Wang, Tao Wang, Su Deng. An endogenous molecular brake preventing APOBEC-driven tumor mutational burden, heterogeneity and therapy resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 93.
Abstract 936: Clinicogenomic predictors for the pattern of failure in high-grade glioma
Authors: Lee Joo Ho , Kang Byung-Hee , Lee Seungbok 
Published: April 2023

Abstract
Background: High-grade gliomas, the most common primary brain tumors, are highly lethal, and treatment options remain limited. Despite advances in genomic technologies, there are few molecular biomarkers to guide precision medicine for high-grade glioma. Here, we aimed to identify the clinicogenomic features associated with its prognosis and recurrence patterns.
Materials/Methods: Our single-institution retrospective analysis included 223 patients diagnosed with high-grade gliomas who underwent next-generation sequencing targeting 82 brain tumor-relevant genes. We categorized them according to the 2021 WHO classification, and their clinicopathological statuses, treatment characteristics, survival, and genomic profiles were analyzed.
Results: The most common genomic variants were TERT promoter (51%), TP53 (39%), IDH1/2 (18%), NF1 (13%), ATRX (12%), PTEN (11%), PIK3CA (9%), SETD2 (7%), and H3F3A (6%) mutation. Regarding copy number variants, amplification of EGFR (21%), PDGFRA (11%), CDK4 (9%) and loss of CDKN2A/2B (55%), PTEN (29%), 19q (17%), NF2 (14%), and RB1 (10%) were the most common copy number aberrations. At a median follow-up of 18 months (range, 2-54 months), 174 patients (78%) had progression or recurrences. A total of 15.2% of our patients were re-classified under the 2021 WHO classification, and there was a clear separation of overall survival(OS) and progression-free survival(PFS) curves between grade 3 and 4 groups using the revised grading system. On multivariate cox regression analysis, MYCN amplification (HR 6.08, p = 0.002) and SETD2 mutation (HR 0.19, p =0.06) were independent predictors of OS and PFS.
Conclusion: The assessment of genomic characteristics in conjunction with the pattern of failure for high-grade glioma aids in identifying patients who are likely to benefit from personalized medicine. The 2021 WHO grading system explains survival differences between grade 3 and 4 tumors better than the 2016 WHO classification dose. We identified SETD2 mutation and MYCN as prognostic biomarkers with potential therapeutic implications in patients with high-grade glioma.
Citation Format: Joo Ho Lee, Byung-Hee Kang, Seungbok Lee. Clinicogenomic predictors for the pattern of failure in high-grade glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 936.
Abstract 973: Uncovering gene signatures of Ewings sarcoma drug sensitivity during the evolution of resistance
Authors: Lin-Rahardja Kristi , Scarborough Jessica , Hitomi Masahiro , Scott Jacob G. 
Published: April 2023

Abstract
The evolution of chemotherapeutic resistance can cause treatment failure in patients with metastatic Ewings sarcoma (EWS), a rare pediatric bone cancer. As resistance to the first-line therapy evolves, there is potential for the tumor to develop sensitivities to other chemotherapeutic agents besides the active treatment. This concept is known as collateral sensitivity, and it presents an opportunity for medical providers to plan more effective treatment regimens. However, it can be difficult to predict due to the stochastic nature of evolution. By analyzing gene expression patterns among independent populations of an EWS cell line that have repeatedly evolved collateral responses, we aim to extract a collection of gene signatures, or sets of genes, that will predict states of collateral sensitivity against various existing chemotherapies.
To accomplish this, we will treat independently evolving replicates of an EWS cell line (A673) with the standard-of-care therapy to evolve resistance. Throughout this treatment regimen, we will regularly screen for collateral sensitivity against 100 FDA-approved cancer drugs and perform bulk RNA-sequencing. When collateral sensitivity against a drug is observed, we will utilize the RNA-sequencing data to extract gene signatures using differential expression analysis. The signatures will then be validated using patient-derived xenografts collected in our lab as well as from collaborators.
When completed, the sizable archive of sensitivity signatures we expect to assemble could greatly streamline the process of treatment planning for EWS patients, especially those with advanced disease. When a patient's response to primary therapy begins to decline, RNA- sequencing can be performed on a tumor biopsy, gene expression patterns can be compared with the validated signature library, and the most appropriate drug for the individual patient can be determined and used for subsequent treatment. Using this method, a patient's sensitivity profile can be reassessed at any point. This proposed method of treatment planning mitigates the need for excessive treatment regimens that are not guaranteed to be effective for every patient, thereby expanding the reach of precision medicine and potentially improving outcomes for EWS patients.
Citation Format: Kristi Lin-Rahardja, Jessica Scarborough, Masahiro Hitomi, Jacob G. Scott. Uncovering gene signatures of Ewings sarcoma drug sensitivity during the evolution of resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 973.
Abstract 998: A blood-based extracellular vesicles DNA methylation signature for colorectal cancer screening
Authors: Zhang Sheng , Wang Faming , Chen Mingxi , Kim Jeongyun , Lu Mengrou , He Hongzhang , Zheng Siyang 
Published: April 2023

Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth leading cause of cancer related deaths, accounting for an estimated 1.8 million new cancer diagnoses and over 880,000 deaths in 2018. Furthermore, CRC patients who are diagnosed at the most advanced (metastatic) stage is estimated to have the 5-year survival rate of 14%. Dramatically, studies shows that if it can be detected at an early stage when surgical removal is feasible, the 5-year survival rate significantly increases to 90%. Therefore, early detection for CRC with curative treatment intent is crucially important to significantly reduce the mortality and morbidity and even cure CRC. Extracellular vesicles (EVs) are lipid-bilayer-enclosed vesicles of sub-micrometer size that are secreted by virtually all cell types. They contain hundreds of different proteins, thousands of intact RNA species, and double-stranded DNA (dsDNA) fragments that sample the entire human genome. Recent findings further corroborate the potential role of EVs in early cancer screening, cancer diagnosis, treatment selection and monitoring. In this study, we used lipid nanoprobe (LNP) for EV isolation and methylation-specific qPCR assay for detecting SEPT9 methylation to develop a minimal invasive CRC screening test. Firstly, we have successfully detected promoter methylation of cancer specific genes SEPT9 in EVs derived from both genomic DNA and EV DNA of the CRC cell line. Secondly, we isolated EV using LNP from plasma samples in a cohort of 19 CRC patients and 9 healthy donor controls. In parallel, we isolated circulating free DNA (cfDNA) from the same cohort of the plasma samples using commercially cfDNA isolation Kit. Then, SEPT9 methylation signature was analyzed by our quantitative real-time PCR assay in these 28 EV DNA samples and 28 cfDNA samples, respectively. In the 19 CRC samples, we identified 10 SEPT9 gene methylation samples from LNP-isolated EV DNA and cfDNA, respectively. In 9 healthy control samples, no SEPT9 methylation was detection in the EV-DNA samples, while one false-positive was detected with cfDNA. Thus, the sensitivity and specificity of EV-DNA in the detection of SEPT9 gene methylation from CRC were determined to be 53% and 100% respectively. In comparison, the sensitivity and specificity of cfDNA are 53% and 89%, respectively from this preliminary pilot study. This indicated that EV-DNA might be superior to cfDNA in detecting SEPT9 gene methylation for CRC screening.
Citation Format: Sheng Zhang, Faming Wang, Mingxi Chen, Jeongyun Kim, Mengrou Lu, Hongzhang He, Siyang Zheng. A blood-based extracellular vesicles DNA methylation signature for colorectal cancer screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 998.
Abstract 999: Colocalization of MAGE-A3 and MAGE-A4 in bladder cancer
Authors: Gilmore Bailey , Gonzalez Rachel , Su Aubrey , Kong Dehe , Zewdu Eden , Yom Jina , Qu Tianli , Guo Zhaoying , Hu Xiaomin , Ren Qi , Zhang Ranran , Christenson Eric , Ma Yan , Yin Dezhong , Yin Patrick , Fu Wei , Liu Xuan , Allampallam Krishnan 
Published: April 2023

Abstract
The treatment of bladder cancers has improved with new immunotherapy such as PD-L1. However, not all bladder cancers respond to PD-L1 immunotherapy which is why new targets are being assessed. Melanoma-associated antigen gene A (MAGE-A) family proteins are expressed in a variety of tumors, with each MAGE-A protein having unique roles in cancer pathogenesis. One advantage of targeting MAGE-A family members is the lack of expression in normal tissues which makes them well-suited for targeted cancer immunotherapy. The challenge with screening the MAGE-A family is to find a specific antibody since the 12-member family has over 60% sequence in homology. In this study, we evaluate multiple MAGE-A3 and MAGE-A4 antibodies using CytoSections, a reproducible alternative to control tissue with an expression of target biomarkers. A series of antibodies specific to each MAGE-A3 and MAGE-A4 protein were discovered and used to screen twenty-five bladder cancer tissues. The results showed that MAGE-A3 was present in 9 of the 25 bladder cancers, while MAGE-A4 was present in 10 of the 25 bladder cancers evaluated; in the meantime, 7 bladder cancers were positive for both targets after double immunofluorescence staining with MAGE-A3 or A4 specific antibodies. The data presented here could be an important development in treatment protocols for pre-screening patients who are at risk. Our findings show that MAGE-A3 and MAGE-A4 can be both present in bladder cancer, suggesting that targeting both genes may be necessary for the success of immunotherapy treatment.
Citation Format: Bailey Gilmore, Rachel Gonzalez, Aubrey Su, Dehe Kong, Eden Zewdu, Jina Yom, Tianli Qu, Zhaoying Guo, Xiaomin Hu, Qi Ren, Ranran Zhang, Eric Christenson, Yan Ma, Dezhong Yin, Patrick Yin, Wei Fu, Xuan Liu, Krishnan Allampallam. Colocalization of MAGE-A3 and MAGE-A4 in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 999.
Abstract SY15-01: Tumor agnostic dendritic cell vaccines
Authors: De Palma Michele 
Published: April 2023

Abstract
Dendritic cells (DCs) are specialized myeloid cells with the ability to uptake, process, and present antigens to T lymphocytes; they also generate cytokine and chemokine gradients that regulate immune cell trafficking, activation, and function. DCs pulsed with tumor antigens have been used as a platform for therapeutic vaccination in cancer. In a broadly tested clinical application called a DC vaccine, autologous monocyte-derived DCs (moDCs) are isolated from a patient with cancer, exposed to tumor antigens ex vivo (antigen loading), and matured before reinfusion to the patient. However, in spite of significant development and testing, DC vaccines based on antigen-loaded moDCs have delivered mixed clinical results. The suboptimal performance of DC vaccines may be due to the use of moDCs - a heterogenous population of non-professional antigen-presenting cells - and the artificial nature of the procedure used to "load" selected tumor antigens on moDCs ex vivo. To address both issues, we developed a DC vaccine that uses a population of mouse or human DC progenitors (DCPs) engineered to produce immunostimulatory cytokines. While not involving antigen loading, the new DC platform outperformed antigen-loaded moDCs in mouse models of cancer. Engineered DCPs produced professional cDC1 and cCD2 in mice, reprogrammed the tumor microenvironment to a form characterized by broad IFNg signaling, and inhibited tumors, including autochthonous models, in an antigen-agnostic fashion. In one application, engineered DCPs synergized with antigen-specific CAR-T cells to eradicate gliomas in mice.
Citation Format: Michele De Palma. Tumor agnostic dendritic cell vaccines. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr SY15-01.
Abstract SY23-02: Mechanistic insights of brain tumor relapse
Authors: Rodriguez-Blanco Jezabel 
Published: April 2023

Abstract
Pediatric brain tumors are the number one cause of cancer-related death in children, with medulloblastoma (MB) being the most common type. Genomic-based classification has enabled the stratification of MB into four distinct molecular subgroups: WNT, Sonic Hedgehog, Group 3, and Group 4. Such classification allows a better understanding of these malignancies, which has resulted in a significant improvement in the stratification of clinical trials. Despite substantial progress made in the field, still, 30% of children with MB will relapse. Recurrent disease in MB is commonly metastatic and virtually none of these patients will live beyond the 1-year hallmark. These sobering statistics underscore the largely unmet need for brain tumor therapies aimed at treating or preventing the emergence of relapsed disease. In this session, we will review recent advances in the identification of treatment-resistant pools of brain tumor cells, giving special emphasis to the signaling mechanisms that allow these cell populations to evade therapeutics and expand.
Citation Format: Jezabel Rodriguez-Blanco. Mechanistic insights of brain tumor relapse. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr SY23-02.
Abstract SY29-01: Integrating evolutionary dynamics into cancer therapy
Authors: Gatenby Robert A. 
Published: April 2023

Abstract
Evolution of resistance remains a barrier to successful therapy in most metastatic cancers despite the increasing number of treatment options. A major driver of the evolutionary capacity of cancer populations is the dynamic interactions of spatial and temporal variations in environmental conditions with malignant cells that can access a vast number of phenotypic properties encoded in the human genome. The research paradigm in cancer treatment remains focused on finding “magic bullets” that can kill all cancer cells while leaving normal cells unharmed - the cure for cancer. Current standard of care principles for metastatic cancers applies one or more drugs as though they were the cure for cancer - continuously at Maximum Tolerated Dose (MTD) until unambiguous evidence of tumor progression. However, because of the phenotypic diversity in most large metastatic cancers, this approach is usually unsuccessful because continuous MTD therapy will eventually kill the population of drug-sensitive cells and leave behind a population of resistant cancer cells that can proliferate unopposed by competition with other populations. I will discuss integration of evolutionary dynamics into cancer therapy. Arguably, this is already widespread because the search for magic bullets and the MTD treatment strategy is built upon an implicit assumption that cancer cure requires a one-cause, one-event extinction similar to the KT impact that eradicated non-avian dinosaurs. However, investigations of recent actual (e.g., Passenger pigeons) and attempted (e.g., pest management) species extinctions in the Anthropocene era have demonstrate more complex dynamics. In fact, most species extinctions are caused by a sequence of perturbations none of which, by itself, could eradicate the population. These dynamics can be integrated into evolution-based treatment approaches to control and perhaps cure currently fatal metastatic cancers with currently available (i.e., non-magic bullet) drugs.
Citation Format: Robert A. Gatenby. Integrating evolutionary dynamics into cancer therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr SY29-01.
Figure S3 from CD86<sup>+</sup> Antigen-Presenting B Cells Are Increased in Cancer, Localize in Tertiary Lymphoid Structures, and Induce Specific T-cell Responses
Authors: Wennhold Kerstin , Thelen Martin , Lehmann Jonas , Schran Simon , Preugszat Ella , Garcia-Marquez Maria , Lechner Axel , Shimabukuro-Vornhagen Alexander , Ercanoglu Meryem S. , Klein Florian , Thangarajah Fabinshy , Eidt Sebastian , Löser Heike , Bruns Christiane , Quaas Alexander , von Bergwelt-Baildon Michael , Schlößer Hans A. 
Published: April 2023

<p>Supplementary Figure 3: TLS accumulate primarily in the invasive margin.</p>