bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6270: Anti-metastatic effects of estrogen receptor β in inflammatory breast cancer
Authors: Nagandla Harika , Tastsoglou Spyros , Cap Kim Cuong , Phillips Aireana , Qian Wei , Zhou Jianying , Chang Jenny , Krishnamurthy Savitri , Ueno Naoto , Hatzigeorgiou Artemis , Thomas Christoforos 
Published: March 2024

Abstract
Inflammatory breast cancer (IBC) is a rare but highly aggressive form of breast cancer with a 5-year survival rate of less than 50%. Although 20-30% of women with IBC have distant metastasis at the time of diagnosis, the biology underlying the aggressive behavior of the disease is poorly understood and molecular markers that distinguish IBC from non-IBC have not yet been identified. In response to the urgent need of discovering new targeted therapies in IBC, we have studied the second estrogen receptor (ERβ) since prior work from our lab correlated higher tumor expression of ERβ in samples from IBC patients with longer metastasis free survival. We showed that ERβ exerted anti-metastatic activity in IBC by inhibiting actin-based cell migration through the suppression of RhoC GTPase signaling. However, since estrogen receptors elicit their effects by inducing global cellular alterations, we have now adopted an integrated genomic approach to fully understand the anti-metastatic effects of ERβ in IBC and delineate the underlying transcriptional regulatory circuits. We found ERβ binding sites in IBC cells and combined this information with gene expression data to identify downstream direct target genes and associated pathways. Our findings suggest the regulation of tumor micro-environment and metabolism as the primary targets of ERβ and we are currently working to pinpoint the crucial regulatory components in these functions. Our findings thus offer an opportunity to better understand the mechanism of ERβ action in aggressive breast cancer, serving as a critical step in validating its tumor repressive role.
Citation Format: Harika Nagandla, Spyros Tastsoglou, Kim Cuong Cap, Aireana Phillips, Wei Qian, Jianying Zhou, Jenny Chang, Savitri Krishnamurthy, Naoto Ueno, Artemis Hatzigeorgiou, Christoforos Thomas. Anti-metastatic effects of estrogen receptor β in inflammatory breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6270.
Abstract 6291: Changes in physical activity and ischemic stroke risk after cancer diagnosis: A nationwide cohort study
Authors: Shin Dong Wook , Jung Wonyoung , Cho In Young , Jung Jinhyung , Cho Mihee , Koo Hye Yeon , Cho Be-Long , Park Jin Ho , Kwon Hyuk Tae , Han Kyungdo , Park Yong-Moon Mark 
Published: March 2024

Abstract
Background: Physical inactivity is prevalent after cancer treatment, which may pose a greater risk of ischemic stroke in cancer survivors.
Objective: To investigate the association between physical activity change from pre- to post-diagnosis and ischemic stroke risk among cancer survivors.
Methods: Cancer survivors without prior history of cardiovascular disease were identified. Pre- and Post-adherence to physical activity was determined within two years from cancer diagnosis. The primary outcome was incident ischemic stroke. Using the Fine-Gray model, sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for ischemic stroke risk were calculated, considering death as a competing risk.
Results: Among 269,943 cancer survivors (mean [SD] age 56.3 [12.1] years, 45.7% male), 10.1% remained active, 11.4% became inactive, and 16.6% became active post-diagnosis. During 1,109,566.68 person-years[YMP1] , remaining active both pre- and post-diagnosis was associated with 15% decreased risk of ischemic stroke (sHR 0.85, 95% CI 0.75-0.96), compared to those who remained inactive. Cancer survivors who became active, and inactive post-diagnosis showed a 16%, and 11% lower risk of ischemic stroke (sHR 0.84, 95% CI 0.75-0.93; sHR 0.89, 95% CI 0.79-0.99) than those who remained inactive.
Conclusions: Our findings suggest that staying physically active is associated with a reduced risk of ischemic stroke among cancer survivors. Notably, these advantages are not limited to individuals who were physically active before their diagnosis, and it is not too late to start post-diagnosis. Preventive strategies against ischemic stroke in cancer survivors should emphasize the incorporation of regular physical activity at any stage of their cancer journey.
Citation Format: Dong Wook Shin, Wonyoung Jung, In Young Cho, Jinhyung Jung, Mihee Cho, Hye Yeon Koo, Be-Long Cho, Jin Ho Park, Hyuk Tae Kwon, Kyungdo Han, Yong-Moon Mark Park. Changes in physical activity and ischemic stroke risk after cancer diagnosis: A nationwide cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6291.
Abstract 6295: Role of MAPK11 in the protective mechanisms against toxicity of tyrosine kinase inhibitors
Authors: Hnatiuk Anna Pavlovna , Staudt David , Mercola Mark 
Published: March 2024

Abstract
Introduction and purpose of the study: Targeted therapies with Tyrosine Kinase Inhibitors (TKIs) have drastically improved the survival of cancer patients. However, long term exposure to TKIs has been associated with severe adverse events such as heart failure, impairing patient survival and life quality, and limiting treatment options. Cardioprotective effect of MAPK11 has been described against cardiac ischemic disease. In addition, MAPK11 has also been reported as an important mediator in cancer development and progression. Therefore the aim of this study is to evaluate the potential therapeutic and dual anti-cancer and cardio-protective effect of MAPK11 inhibition during TKI treatment.
Experimental procedures: For this study we used the TKI ponatinib as a paradigm of cardiac toxicity. Ponatinib has been used as a gold standard therapy for the drug resistant type of Chronic Myeloid Leukemia (CML) due to T315I-ABL1 mutation, and has been associated with high risk of cardiac toxicity. We performed in vitro functional assays to evaluate the cardiotoxicity and cardiac protection using human iPSC-cardiomyocytes (hiPSC-CMs), and anti-cancer effect in T315I mutated KCL-22 CML cells. The cardiotoxicity was evaluated by impairment of cardiomyocytes contractile function during TKI (ponatinib) treatment, the cardiac-protection was evaluated by restoration of contractile function post-inhibition of MAPK11 with RNA silencing (siRNA) technique. The anti-cancer effect was evaluated using a cell viability and proliferation assay during inhibition of MAPK11 by siRNA and ABL1 inhibition as a positive control.
Summary of unpublished data: Pretreatment with siRNA MAPK11 inhibition significantly improved the contractile function of the cardiomyocytes during treatment with ponatinib when compared to those that did not receive MAPK11 inhibition. Moreover, when compared to the positive control of siRNA ABL1 inhibition, the MAPK11 inhibition showed similar anti-cancer effect in the T315I mutated KCL-22 CML cells proliferation and survival assay.
Conclusions: Our study suggests that the inhibition of MAPK11 is a potential druggable therapeutic target with dual action of anti-cancer effect for the mutant form of CML, as well as a substantial protective effect against the cardiac toxicity associated with the TKI ponatinib that could bring insights in the development of safer oncological drugs.
Citation Format: Anna Pavlovna Hnatiuk, David Staudt, Mark Mercola. Role of MAPK11 in the protective mechanisms against toxicity of tyrosine kinase inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6295.
Abstract 6311: From bench to bedside: GMP manufacturing and testing of an LGR5-targeting CAR-T against colorectal cancer
Authors: Bandara Veronika , Gundsambuu Batjargal , Napoli Silvana , Foeng Jade , McPeake Dylan , Tylis Timona , Thompson Emma , Mills Stuart , Cowin Allison , Bonder Claudine , Sadlon Timothy , McColl Shaun , Barry Simon 
Published: March 2024

Abstract
Colorectal cancer is the third most diagnosed cancer worldwide, and is responsible for the second largest number of cancer related deaths, warranting the need for new treatments. The successful use of chimeric antigen receptor T (CAR-T) cells against B-cell malignancies has inspired the search for CAR-T cell therapies against solid tumours such as colorectal cancer. Cancer stem cells (CSC) are a small population of cells within a tumour with the capacity to self-renew, differentiate, and initiate new tumours. CSC are resistant to chemotherapy and radiotherapy and are enriched in residual disease. Targeting CSC is a strategy to reduce the tumours’ ability to generate new cells. Leucine-rich G protein-coupled receptor 5 (LGR5) is a marker of CSC and LGR5+ cancer cells are implicated in tumour progression and metastasis in colorectal cancer. We designed and tested a chimeric antigen receptor (CAR) targeting the extracellular domain of LGR5. LGR5-targeting CAR-T cells showed significant antigen-specific cytotoxicity and IFNγ release against colorectal cancer (CRC) cell lines in vitro, and in vivo efficacy in a CRC xenograft mouse model. We confirmed the specificity and safety of the LGR5 targeting CAR-T cells by testing against normal human tissues. A GMP ready protocol for clinical scale manufacture of LGR5-targeting CAR-T cells have been developed using CD3+ T-cells from healthy donors. We have successfully tested this protocol using CRC patient-derived CD3+ T-cells and were able to generate clinically relevant cell numbers (80-fold expansion) with high CAR expression. Cells manufactured using this GMP protocol expressed markers of self-renewing naïve-like and central memory phenotype and showed very low percentage of cells that were triple-positive for PD1, TIM3 and LAG3. This protocol has been successfully tested and validated in a GMP manufacturing facility for the production of LGR5 targeting CAR-T cells, in preparation for an FDA approved first in man clinical trial against metastatic colorectal cancer, starting in 2023 (NCT05759728).
Citation Format: Veronika Bandara, Batjargal Gundsambuu, Silvana Napoli, Jade Foeng, Dylan McPeake, Timona Tylis, Emma Thompson, Stuart Mills, Allison Cowin, Claudine Bonder, Timothy Sadlon, Shaun McColl, Simon Barry. From bench to bedside: GMP manufacturing and testing of an LGR5-targeting CAR-T against colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6311.
Abstract 6430: Gene expression signature quantifies the cellular contribution of the tumor vs. the microenvironment in determining colorectal cancer prognosis and therapeutic outcome
Authors: Yang Mingli , Yeatman Timothy J. , Nebozhyn Michael V. , Schell Michael J. , Pflieger Lance , Loboda Andrey , Pledger Warren J. , Soundararajan Ramani , Maurin Michelle , Wang Heiman , Silva Jetsen Rodriguez , Alden Ashley 
Published: March 2024

Abstract
Accumulating evidence has suggested that cancer progression and therapeutic response may depend on not only tumor cells but also their tumor microenvironment (TME). However, their contributory roles are complex and not well understood. Here we report an analysis of 2373 human colorectal cancer (CRC) tumors representing all stages, leading to identification of a 20-gene signature capable of quantifying the cellular contribution of the tumor vs. the TME in determining colorectal cancer prognosis and therapeutic outcome. We classified these tumors into the consensus molecular subtypes (CMS1-4) with distinct, variable TME cellular features defined by CIBERSORT deconvolution analysis of bulk gene expression data. Surprisingly, all the 10 positive signature genes (portending worse survival) were strongly correlated with the TME-rich CMS1 and CMS4 tumors. By contrast, all the 10 negative signature genes (portending better survival) were highly related to the TME-poor CMS2 and CMS3 tumors. A single cell expression analysis from an independent database further revealed that strikingly, all the 10 positive genes were principally expressed by the immune/stromal TME whereas all the 10 negative genes were predominantly expressed in epithelial tumor cells. These data suggest that the TME has an equally important role as do tumor cells in determining CRC prognosis and support targeting the TME to improve survival. Moreover, distinct gene expression from tumor cells versus the TME also showed a differential impact on therapeutic outcome. Retrospective analyses on two independent clinical trial datasets show that the 20-gene signature score significantly predicted progression free survival in metastatic CRC patients treated with cetuximab, an FDA-approved EGFR inhibitor therapy. These data suggest a potential for the 20-gene signature as a predictive biomarker to identify “sensitive” versus “resistant” subpopulations of CRC patients to improve outcome of EGFR-targeted therapy.
Citation Format: Mingli Yang, Timothy J. Yeatman, Michael V. Nebozhyn, Michael J. Schell, Lance Pflieger, Andrey Loboda, Warren J. Pledger, Ramani Soundararajan, Michelle Maurin, Heiman Wang, Jetsen Rodriguez Silva, Ashley Alden. Gene expression signature quantifies the cellular contribution of the tumor vs. the microenvironment in determining colorectal cancer prognosis and therapeutic outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6430.
Abstract 6436: Tumor-educated platelets for therapy stratification of metastasized castration resistant prostate cancer (CRPC)
Authors: Nilsson Jonas A. , Lundholm Marie , Tjon-Kon-Fat Lee-Ann , Köhn Linda , Thellenberg-Karlsson Camilla , Josefsson Andreas , Wikström Pernilla 
Published: March 2024

Abstract
One in ten men diagnosed with prostate cancer will have metastases. At some point the metastases becomes castration therapy resistant, contributing leading to the high mortality of prostate cancer. Novel androgen directed treatments, like abiraterone and enzalutamide, have made substantial difference to therapy response, yet only within subgroups of CRPC patients. Correct therapy stratification may prolong the life of the patients, possibly turning a deadly disease into a more chronic disease. For this to happen we need predictive biomarkers that can be used to longitudinally follow the disease in order to identify vulnerabilities and to monitor acquired resistance, e.g. we need to develop personalized liquid biopsy platforms. Using the platelet enriched fraction of a blood sample we here show that we can use the platelets ability to sequester material during circulation to provide information derived from the tumor, a.k.a. tumor-educated platelets. This information could be used as a companion diagnostic to identify patients that will respond to therapy, and to longitudinally monitor tumor progression. In this study, a previously published three gene profile, plt3G profile, was validated in a larger cohort (n=97) and showed that combined analysis of the three genes transcripts (KLK3, FOLH1, NPY) could be used to identify long-term responders regarding progression-free survival after enzalutamide (n=47; PFS; LR p&lt;0,001, HR 0,32, p&lt;0,001) or abiraterone (n=50; PFS; LR p=0.007, HR 0.45, p=0,009) -treatment. Furthermore, progression and resistance development could be accurately longitudinal followed. The plt3G profile showed a significant overlap with circulating tumor DNA (ctDNA) biomarkers, but in addition also provided predictive information around treatment response. Tumor-educated platelets provide therapy-predictive biomarkers as well as biomarkers for longitudinal monitoring of disease progression and resistance development, which ultimately could provide information for therapy switching. Their easy accessibility makes tumor-educated platelets an attractive biosource to be used alone or in combination others, to enable a fluid biomarker platform with the aim to turn a lethal cancer disease into a more chronic disease.
Citation Format: Jonas A. Nilsson, Marie Lundholm, Lee-Ann Tjon-Kon-Fat, Linda Köhn, Camilla Thellenberg-Karlsson, Andreas Josefsson, Pernilla Wikström. Tumor-educated platelets for therapy stratification of metastasized castration resistant prostate cancer (CRPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6436.
Abstract 6445: Exploring the relationship between PSCA and PD-L1 by a comprehensive tumor immunohistochemical analysis
Authors: Guo Yichen , Gonzalez Rachel , Yom Jina , Gilmore Bailey , Qu Tianli , Hu Xiaomin , Han Andy (Xi) , Guo Zhaoying , Zewdu Eden , Liu Xuan , Fu Wei 
Published: March 2024

Abstract
Prostate Stem Cell Antigen (PSCA) is a well-established diagnostic marker in various cancers and a promising target for immunotherapy. Programmed Death-Ligand 1 (PD-L1) plays a crucial role in cancer immune regulation and is known to influence patient response to checkpoint inhibitors. The objective of this study is to elucidate the relationship between PSCA and PD-L1 in diverse cancer types and to provide valuable insights for the development of an effective immunotherapy strategy.
To accomplish this, immunohistochemical (IHC) analysis was conducted on paraffin-embedded Cytosections obtained from 20 lung cancers, 20 prostate cancers, 32 bladder cancers, and 20 normal tissues for each respective cancer type. Antibodies generated by Origene were utilized to detect the expression of PSCA and PD-L1 on the cell surface. The IHC results of tumor tissue were standardized against corresponding normal samples, and the correlation between these two genes was statistically analyzed using analysis of variance (ANOVA). The findings reveal a significant positive correlation between the expression of PSCA and PD-L1 (r=+0.78, P=0.016), suggesting an underlying mechanism driving their co-expression in the studied cancers.
Understanding PSCA and PD-L1 coexpression in bladder, lung, and prostate cancers has great potential for informing tailored immunotherapies. Future research should explore functional consequences within the tumor microenvironment, advancing precision immunotherapy for improved outcomes in these challenging malignancies.
Citation Format: Yichen Guo, Rachel Gonzalez, Jina Yom, Bailey Gilmore, Tianli Qu, Xiaomin Hu, Andy (Xi) Han, Zhaoying Guo, Eden Zewdu, Xuan Liu, Wei Fu. Exploring the relationship between PSCA and PD-L1 by a comprehensive tumor immunohistochemical analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6445.
Abstract 6499: The landscape of MET exon 14 skipping mutations in non-small cell lung cancer patients identified by next-generation sequencing
Authors: Shi Chen , Ning Gao , Qinglan Zong 
Published: March 2024

Abstract
Background: MET exon 14 skipping mutations (METex14) account for approximately 0.9%-4% in patients with non-small cell lung cancer (NSCLC). The primary detection methods are DNA and RNA-based next-generation sequencing (NGS). However, the effect of amplicon-based library construction (ALC) and capture-based library construction (CLC) on the detection characteristics of METex14 during the NGS process is not yet fully understood. Here we described the landscape of METex14 in NSCLC patients, as identified by NGS using two different library construction methods.
Methods: A total of 6811 samples with NSCLC were enrolled in this study, including 3839 samples performed by DNA-based NGS with CLC, 64 samples performed by RNA-based NGS with CLC and 2908 samples performed by the synchronous DNA-based and RNA-based NGS with ALC. Only the pathogenic mutations and likely pathogenic mutations in clinical significance were rolled into our analysis.
Results: The ranking of different methods, as determined by the positive rates for METex14, was RNA-based NGS with ALC (71/2908, 2.44%), RNA-based NGS with CLC (1/64, 1.56%), DNA-based NGS with CLC (54/3839, 1.41%) and DNA-based NGS with ALC (14/2908, 0.48%). Out of 2908 samples performed by the synchronous DNA-based and RNA-based NGS with ALC, 73 samples (2.51%) had METex14 detected at either the DNA or RNA level. METex14 were only detected at the RNA level in 59 patients, while they were only detected at the DNA level in 2 patients. This might be due to the limited probe design at DNA level and the Y1003 site which could not be detected at RNA level. As revealed by DNA-based NGS, the mutation forms causing METex14 include point mutations, indels, and large segment duplications. And the highest mutation rate is in the splice donor site (30.9%), the lowest is observed at position Y1003 (2.9%). Additionally, METex14 is more prevalent in patients over 60 years of age in Chinese NSCLC, with a statistically significant difference (P=0.0043).
Conclusion: RNA-based detection of MET 14 skipping yielded a higher detection rate compared to DNA-based NGS, regardless of ALC or CLC. Combining DNA and RNA analysis is more suitable for detecting MET exon 14 skipping and increases the positive rate.
Citation Format: Chen Shi, Gao Ning, Zong Qinglan. The landscape of MET exon 14 skipping mutations in non-small cell lung cancer patients identified by next-generation sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6499.