bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1097: CD73 contributes to the pathogenesis of fusion-negative rhabdomyosarcoma through the purinergic signaling pathway
Authors: Hernandez Karla Gabriela Cano , Shah Akansha , Lopez Victor , Tagliabracci Vincent , Chen Kenian , Xu Lin , Bassel-Duby Rhonda , Olson Eric , Liu Ning 
Published: March 2024

Abstract
Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and adolescents. Fusion-Negative RMS (FN-RMS) accounts for more than 80% of all RMS cases. The long-term event-free survival rate for patients with high grade FN-RMS is below 30%, highlighting the need for improved therapeutic strategies. CD73 is a 5’ ectonucleotidase that hydrolyzes AMP to adenosine and regulates the purinergic signaling pathway. We found that CD73 is elevated in FN-RMS tumors that express high levels of TWIST2. While high expression of CD73 contributes to the pathogenesis of multiple cancers, its role in FN-RMS has not been investigated. We found that CD73 knockdown decreased FN-RMS cell growth while upregulating the myogenic differentiation program. Moreover, mutation of the catalytic residues of CD73 rendered the protein enzymatically inactive and abolished its ability to stimulate FN-RMS growth. Overexpression of wildtype CD73, but not the catalytically inactive mutant, in CD73 knockdown FN-RMS cells, restored their growth capacity. Likewise, treatment with an adenosine receptor A2A-B agonist partially rescued FN-RMS cell proliferation and bypassed the CD73 knockdown defective growth phenotype. These results demonstrate that the catalytic activity of CD73 contributes to the pathogenic growth of FN-RMS through the activation of the purinergic signaling pathway. Therefore, targeting CD73 and the purinergic signaling pathway represents a potential therapeutic approach for FN-RMS patients.
Citation Format: Karla Gabriela Cano Hernandez, Akansha Shah, Victor Lopez, Vincent Tagliabracci, Kenian Chen, Lin Xu, Rhonda Bassel-Duby, Eric Olson, Ning Liu. CD73 contributes to the pathogenesis of fusion-negative rhabdomyosarcoma through the purinergic signaling pathway [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 1097.
Abstract 110: Adoptive transfer of tumor antigen-specific T cells alters the renal tumor microenvironment in the presence and absence of immunotherapy
Authors: Stephens Holly , Elkins Elizabeth , Dempsey Francesca , Swalley Zoey , Li Jing , Zhang Jianqing , Kirkman Richard , Chen Bo-Ruei , Roberts Zachary , Sudarshan Sunil , Sleckman Barry , Tse Hubert , Smith Daniel L. , Norian Lyse A. 
Published: March 2024

Abstract
Immunotherapies are the standard of care for patients with renal cancer, yet their effects on renal tumor antigen-specific CD8 T cell responses and their subsequent ability to modulate the renal tumor microenvironment remain difficult to evaluate. In order to address this gap in the field, we developed a novel murine model to examine tumor-antigen specific CD8 T cell immune responses in orthotopic renal cancer utilizing a new cell line, Renca-tERK-LUC. Parental Renca cells were transduced with a lentivirus expressing the naturally-occurring, mutated tERK peptide found in CMS5 fibrosarcoma cells to create Renca-tERK-LUC tumor cells. The tERK mutation consists of a one base pair change that creates an Sfc1 site, so it can be detected by RT-PCR followed by restriction enzyme digestion. Our data show that Renca-tERK-LUC cells express tERK at high levels and grow progressively in control BALB/c mice, but are rejected in DUC Thy1.1 mice, which contain endogenous TCR transgenic CD8+ T cells specific for tERK peptide/MHC I complexes. We then performed adoptive transfers of 5 × 105 DUC Thy1.1 T cells into mice with established, orthotopic Renca-tERK-LUC tumors to evaluate: 1) the effects of immunotherapy on tumor-antigen-specific T cell responses; and 2) the effects of tumor-antigen-specific T cells on the broader renal tumor microenvironment. Our data indicate that the transfer of relatively low numbers of tumor antigen-specific CD8+ T cells induces transcriptomic and cellular changes in the tumor microenvironment in both the presence and absence of immunotherapy. Defining the parameters surrounding tumor-antigen-specific T cell responses and their ability to modulate the renal tumor microenvironment under the influence of clinically relevant immunotherapeutic intervention has the potential to increase the understanding of immunity to renal tumors, which could ultimately prove beneficial for renal cancer patients.
Citation Format: Holly Stephens, Elizabeth Elkins, Francesca Dempsey, Zoey Swalley, Jing Li, Jianqing Zhang, Richard Kirkman, Bo-Ruei Chen, Zachary Roberts, Sunil Sudarshan, Barry Sleckman, Hubert Tse, Daniel L. Smith, Lyse A. Norian. Adoptive transfer of tumor antigen-specific T cells alters the renal tumor microenvironment in the presence and absence of immunotherapy [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 110.
Abstract 1102: Amentoflavone enhances regorafenib-induced apoptosis and -inhibited invasion via inactivating STAT3/NF-ΚB signaling pathway in Hepatocellular carcinoma
Authors: Tsai Yan ting , Chen Ying-Tzu , Hsu Fei-Ting , Tsai Jai-Jen , Liu Yu-Chiang 
Published: March 2024

Abstract
Hepatocellular carcinoma (HCC) is an aggressive tumor and ranks as the third leading cause of cancer-related deaths worldwide. Amentoflavone, a biflavonoid compound, possesses antiviral, angiogenesis-inhibitory, and anticancer properties. Prior studies have illustrated that amentoflavone effectively restrains tumor growth and promotes apoptosis in various cancers, including brain cancer and osteosarcoma. Regorafenib, a small molecule inhibitor of multi-kinases, can inhibit angiogenesis, tumor growth, and anti-tumor metastasis. While regorafenib is a targeted drug approved for the treatment of metastatic colorectal cancer and has also been approved for use in HCC, its effectiveness in HCC is limited. Consequently, our goal is to investigate whether amentoflavone may enhance the sensitivity of regorafenib in treating HCC and explore the underlying mechanisms. In our study, through the combined treatment and combination index analysis, we proved that the combination of regorafenib and amentoflavone may induce cytotoxicity more effectively compared to monotherapy, as assessed by the MTT assay in Huh7 and HepG2 cells. The invasion and migration assays also demonstrated a superior inhibitory effect in the combination group. Additionally, apoptosis markers such as "cleaved caspase-3, -8, -9, Fas and FasL" assayed by flow cytometry, confirm that the combination treatment may induce the extrinsic/intrinsic apoptosis pathway in HCC. In our Western blotting analysis, we observed that the phosphorylation of STAT3 and NF-κB proteins was effectively suppressed by the combination of regorafenib and amentoflavone in Huh7 and HepG2 cells, respectively. Furthermore, our in vivo study confirmed a superior tumor inhibition rate and control rate with the combination of regorafenib and amentoflavone. Importantly, no signs of general toxicity were observed in any of the treatment groups, as evidenced by body weight monitoring and Hematoxylin and Eosin stain (H&E) pathology evaluation. We believe that the combined treatment of these two drugs effectively triggers cell death and suppresses metastatic patterns through the inactivation of the STAT3/NF-κB signaling pathway. These results suggest that amentoflavone has the potential to serve as an adjuvant that sensitizes regorafenib for the treatment of HCC without causing any side effects.
Citation Format: Yan ting Tsai, Ying-Tzu Chen, Fei-Ting Hsu, Jai-Jen Tsai, Yu-Chiang Liu. Amentoflavone enhances regorafenib-induced apoptosis and -inhibited invasion via inactivating STAT3/NF-ΚB signaling pathway in Hepatocellular carcinoma [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 1102.
Abstract 1147: Sub-cellular spatial resolution of immune and stromal interactions underlying prostate cancer progression
Authors: Mo Chia-Kuei , Jayasinghe Reyka G. , Abedin do Ateih , Li Xiang , Weimholt Cody , Kim Eric H. , Pachynski Russell , Chen Feng , Ding Li 
Published: March 2024

Abstract
Prostate cancer boasts a complex morphological structure and diverse cellular composition, yet current technology falls short in resolving the detailed spatial interactions among cells within the environment. In this study, we employed the Xenium platform, coupled with the 3D reconstruction tool Mushroom, to examine high-resolution spatial cellular interactions within the prostate cancer microenvironment. Our investigation focused on the transition of molecular characteristics from normal to high-grade prostatic intraepithelial neoplasia (HGPIN, pre-cancer), spanning the spectrum of Gleason Grades 3 to 4 and advancing to metastatic prostate cancer. We identified genes with unique spatial and grade-dependent expression profiles, including MYC, CP, and UHCL1. Evaluating sub-cellular imaging facilitated a comprehensive characterization and quantification of immune and stromal interactions, unveiling distinct spatial niches across transition stages. These findings underscore the nuanced immune interactions within the tumor microenvironment and offer crucial insights into the development of immunotherapeutic approaches tailored to the specific spatial and immune dynamics observed in advanced prostate cancer. This research contributes to the evolving understanding of prostate cancer progression, providing a foundation for the development of targeted therapies that disrupt specific cellular interactions.
Citation Format: Chia-Kuei Mo, Reyka G. Jayasinghe, Ateih Abedin do, Xiang Li, Cody Weimholt, Eric H. Kim, Russell Pachynski, Feng Chen, Li Ding. Sub-cellular spatial resolution of immune and stromal interactions underlying prostate cancer progression [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 1147.
Abstract 1217: Defining the anti-tumor activity and immune effects of the RASMULTI(ON) inhibitor RMC-7977 in preclinical models of NRAS-mutant melanoma
Authors: Carvalho Larissa A. , Phadke Manali S. , Smalley Keiran S. M. 
Published: March 2024

Abstract
Introduction: Mutations in the small GTPase NRAS are the second most common oncogenic driver in cutaneous melanoma, being found in ~25% of cases. Targeted therapy strategies are currently lacking for NRAS-mutant melanoma. Here, we characterized the anti-tumor activity and immune effects of RMC-7977, a RASMULTI(ON) preclinical tool compound, representative of the investigational agent RMC-6236, in preclinical mouse and human models of NRAS-mutant melanoma.
Methods: The in vitro potency of RMC-7977 was determined using mouse and human NRAS-mutant melanoma cell lines. Recovery of signaling was quantified by Western Blot and receptor tyrosine kinase (RTK) arrays. In vivo anti-tumor activity of RMC-7977 was determined in two syngeneic mouse melanoma models (SW1 NRASG13D and NRAS#5 NRASQ61R), and tumor immune infiltrate quantified using multiplexed IHC and flow cytometry. Mechanisms of resistance were defined using RNA-seq.
Results: RMC-7977 had good activity in vitro against human cancer cell lines and in mouse models of NRAS-mutant melanoma. Time-course studies demonstrated RMC-7977 rapidly inhibited phospho-ERK signaling, which then began to recover after 8 hr of treatment. There was also evidence of adaptive receptor tyrosine kinase signaling by 48 hr. In syngeneic mouse models of NRAS-mutant melanoma, RMC-7977 led to a rapid inhibition of tumor growth, increased expression of tumor MHC class I and PD-L1 and an increase in CD4+ and CD8+ T cell infiltrate into tumors. Therapeutic escape was associated with decreased CD4+ and CD8+ T cell infiltration and increased numbers of immunosuppressive MDSCs. Cells collected from tumors resistant to RMC-7977 in vivo did not show any shift in sensitivity to the inhibitor when re-challenged in vitro, suggesting that the resistance observed in vivo resulted from mechanisms specific to the tumor microenvironment, for example adaptive RTK signaling or immune escape. RNA-seq and IHC analysis suggested that resistance was associated with decreased MHC expression and antigen presentation, as well as reduced co-stimulation of T cells. Combination studies of RMC-7977 with anti-PD-1 are ongoing to identify potential synergistic interactions in these preclinical models.
Conclusion: RMC-7977 has anti-tumor activity in syngeneic mouse models of NRAS-mutant melanoma, associated with a robust immune response.
Citation Format: Larissa A. Carvalho, Manali S. Phadke, Keiran S. M. Smalley. Defining the anti-tumor activity and immune effects of the RASMULTI(ON) inhibitor RMC-7977 in preclinical models of NRAS-mutant melanoma [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 1217.
Abstract 1271: PMEPA1 acts as a switch to modulate cooperative cellular invasion and drive NSCLC tumor progression
Authors: Khatib Tala O. , Pedro Brian A. , Knippler Christina M. , Matsuk Veronika Y. , Webster Sarah F. , Bombin Sergei , Dwivedi Bhakti , Kowalski Jeanne , Johnston Henry R. , Mouw Janna K. , Marcus Adam I. 
Published: March 2024

Abstract
Metastatic disease drives cancer patient mortality. One primary mode of metastasis is collective invasion, whereby cohesive groups of cells invade into the adjacent stroma while maintaining cell-cell contacts. Importantly, these cellular packs harbor genetically and phenotypically heterogeneous subpopulations that cooperate to drive invasion. To deconstruct how phenotypic cellular heterogeneity facilitates distinct molecular profiles within a single tumor, we established the technique Spatiotemporal Cellular and Genomic Analysis (SaGA). SaGA is an image-guided approach that optically highlights phenotypically defined cell(s) for live fluorescence-activated cell sorting and analysis. To elucidate the transcriptional heterogeneity across invasive packs within a 3D physiologically-relevant microenvironment, we combined SaGA with single cell RNA sequencing for isolation and analysis of actively invading cells. This novel single cell transcriptomics approach reveals that - during cellular invasion into the microenvironment - the follower subpopulation supplies TGFβ to heterogeneously stimulate both autocrine canonical and paracrine noncanonical signaling pathways. This cooperative exchange facilitates a symbiotic relationship between tumor subpopulations in non-small cell lung carcinoma both in vitro and in vivo. In vitro, we determine that PMEPA1 protein levels mitigate TGFβ downstream effector signaling within heterogeneous tumor cells to modulate JAG1 expression and activity. In vivo, we show that a reduction in JAG1 levels decreases primary tumor cell invasion and progression. We mechanistically define a TGFβ-PMEPA1-JAG1 signaling axis across leader and follower subpopulations critical for tumor cell invasion and cancer progression. Together, these data highlight the importance of cellular heterogeneity and subpopulation communication required for tumor progression.
Citation Format: Tala O. Khatib, Brian A. Pedro, Christina M. Knippler, Veronika Y. Matsuk, Sarah F. Webster, Sergei Bombin, Bhakti Dwivedi, Jeanne Kowalski, Henry R. Johnston, Janna K. Mouw, Adam I. Marcus. PMEPA1 acts as a switch to modulate cooperative cellular invasion and drive NSCLC tumor progression [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 1271.
Abstract 1278: Differential urinary microbiome and its metabolic footprint in bladder cancer patients following BCG treatment
Authors: Piao Xuan-Mei , Min Kyungchan , Byun Young Joon , Zheng Chuang-Ming , Kim Seon-Kyu , Park Seong-Hwan , Moon Sungmin , Kim Kyeong , Kang Ho Won , Kim Won Tae , Yun Seok Joong , Park Hansoo 
Published: March 2024

Abstract
Introduction & Objectives: Recent insights reveal a urinary microbiome, challenging prior beliefs about urine's sterility. Using 16S rRNA gene sequencing, a pivotal tool in mapping this microbiome, our study delves into the interplay between bladder cancer (BCa), BCG therapy, and the urinary microbiome. We analyzed bacterial profiles in benign and malignant samples, considering various clinical parameters.
Materials & Methods: A total of 88 patients participated in the study, comprising 30 individuals with benign diseases and 58 BCa patients. Urine samples were collected from patients with benign conditions and from BCa patients before and after BCG treatment. Malignant samples obtained before the completion of the intravesical BCG induction cycle were labeled 'Pre-BCG', while those collected after this cycle were termed 'Post-BCG'. Following collection, DNA was extracted and underwent 16S rRNA gene sequencing. The sequencing data was then utilized for bioinformatic analyses, which included metagenomic profiling and metabolic pathway inference.
Results: Significant differences in bacterial compositions were observed between benign and malignant samples, with a metabolic signature suggesting toluene degradation pathway may mitigate bladder cancer development. In the post-BCG samples, we inferred elevations of 2-oxoglutarate, a BCG derivative, and L-methionine, which is associated with therapeutic benefits, compared to their pre-BCG counterparts. Furthermore, post-BCG samples showed microbial differences in responders and increased quinolone synthesis compared to non-responders. This is of significance due to quinolone's role in modulating DNA topoisomerase and mitochondrial functions, both pivotal in bladder cancer progression.
Conclusions: Utilizing 16S rRNA gene sequencing, we drew comparisons between the urinary microbiomes of benign and malignant samples and suggested a potential pathway for bladder cancer occurrence. Following intravesical BCG treatment, certain microbial metabolic pathways seemed to offer therapeutic benefits to responders. Our study provides insights into the microbial influences on bladder cancer development and the varying responses to BCG treatment.
Citation Format: Xuan-Mei Piao, Kyungchan Min, Young Joon Byun, Chuang-Ming Zheng, Seon-Kyu Kim, Seong-Hwan Park, Sungmin Moon, Kyeong Kim, Ho Won Kang, Won Tae Kim, Seok Joong Yun, Hansoo Park. Differential urinary microbiome and its metabolic footprint in bladder cancer patients following BCG treatment [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 1278.
Abstract 1324: Superior anti-tumor activity of GL205, an allogeneic anti-CD5 CAR-NK for treating T-cell malignancies
Authors: Jung Miyoung , Kim Seung Min , Lee Eunsol , Sun Hyunseung , Yoo Jaeyoung , Choi Hwi Wan , An Subin , Cho Sunglim , Min Bokyung 
Published: March 2024

Abstract
T cell malignancies are rare and intractable diseases with fewer treatment options and higher unmet needs compared to B-cell lymphomas. Chemotherapy such as CHOP has been used as the standard therapy for treatment of T cell malignancies, but clinical outcome is not a promising and alternative treatments are needed. Currently, Brentuximab Vedotin, an antibody-drug conjugate that targets CD30 is widely used for Hodgkin lymphoma, ALCL and CTCL. However, the application is limited to specific subtypes because CD30 expression is restricted to some subsets of T-cell lymphoma. CD5 is an attractive target for cancer immunotherapy because it is commonly expressed in most of T cell malignancies. Although CD5 CAR-T cell products have demonstrated the anti-cancer efficacy, there are several disadvantages including 1) challenges due to difficulties in manufacturing process caused by fratricide, 2) product contamination by CAR-introduced patient’s malignant T cells, 3) severe side effects such as CRS and neurotoxicity. Therefore, CD5 CAR-NK as allogeneic anti-tumor therapy can be an alternative for treatment of T cell malignancies. GL205, cord blood-derived CD5 CAR-NK, is genetically modified to express CD5-directed CAR and simultaneously produce IL-15 which supports the NK survival and proliferation. GL205 is ex-vivo expanded, cryopreserved cell therapy product comprising of pure NK cells (&gt; 99%) with high CD5 CAR expression (&gt; 90%). GL205 showed significantly higher in vitro direct-killing efficacy against CD5+ tumor cells compared to donor matched CBNK. IFN-γ and IL-15 release from GL205 was significantly increased after co-incubation with CD5+ tumor cells. In xenograft mouse model, GL205 administration exhibited a greater survival rate and low tumor burden compared to vehicle group. In addition, GL205 was detected in blood for 3 months, demonstrating in vivo long-term persistence. In conclusion, GL205 could be a valuable and off-the-shelf allogeneic therapeutic option for treating T cell malignancies.
Citation Format: Miyoung Jung, Seung Min Kim, Eunsol Lee, Hyunseung Sun, Jaeyoung Yoo, Hwi Wan Choi, Subin An, Sunglim Cho, Bokyung Min. Superior anti-tumor activity of GL205, an allogeneic anti-CD5 CAR-NK for treating T-cell malignancies [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 1324.