bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6698: Tumor microbiota associated with immune enrichment in breast tumor
Authors: Yeo Li-Fang , Lim Bernard KB , Islam Tania , Teoh Li-Ying , Jamaris Suniza , See Mee-Hoong , Looi Lai-Meng , Taib Nur Aishah Mohd , Yip Cheng-Har , Rajadurai Pathmanathan , Teo Soo-Hwang , Pan Jia Wern 
Published: March 2024

Abstract
Asian cancer patients have enriched immune profiles when compared to Caucasians. This is associated with improved overall survival and potentially better response to immunotherapy. Yet the reason behind enriched Asian immune profiles is unclear. This study investigated microbes found in Malaysian breast tumors in association with immune profiles. We used an existing dataset of RNA-seq data from fresh frozen breast tumor tissue (n=978). Sequencing reads were trimmed and filtered to remove human reads. Non-human reads were mapped to Kraken2 and relative abundance was estimated using Bracken. Microbiome analysis was conducted on R following Microbiome OMA guidebook. The top five genera found in the Malaysian Breast Cancer (MyBrCa) cohort were Pseudomonas, Siphoviridae, Bacillus, Escherichia and Klebsiella. Alpha diversity of basal subtype microbiota was significantly higher than Her2 subtype (Shannon index, p=0.027) whilst the other subtypes were more homogenous. MyBrCa patients with low immune scores were significantly different from high immune scores while controlling for age, stage, grade, ethnicity and PAM50 subtype (PERMANOVA, F-statistic = 1.656, p=0.05). Differential abundance analysis revealed Sulfidibacter and Priestia to be significantly different in abundance between high vs low IFNg groups (FDR-adjusted p-value &lt; 0.05) using ALDEx2, ANCOM-BC2 and ZicoSeq and LinDA algorithms. Sulfidibacter was significantly different between high vs low immune group for Bindea combined immune score and ESTIMATE score groups (FDR-adjusted p-value &lt;0.05). An independent breast cancer cohort (n=419) was used as validation where Sulfidibacter and Priestia were also significantly different in abundance for immune high vs low groups. Machine learning using Random Forest model predicted immune group with an AUC of 0.79 (CI = 0.74, 0.83; p-value &lt; 0.01). The top five most important features contributing to the random forest model were Sulfidibacter, Prestia, Cutibacterium, Acinetobacter and Rhizobium. This study is the largest to date that characterize the tumor microbiota of an Asian cohort of breast cancers, where Sulfidibacter and Priestia, both relatively new and uncharacterized bacteria, were differentially abundant among patients with high vs low immune scores.
Citation Format: Li-Fang Yeo, Bernard KB Lim, Tania Islam, Li-Ying Teoh, Suniza Jamaris, Mee-Hoong See, Lai-Meng Looi, Nur Aishah Mohd Taib, Cheng-Har Yip, Pathmanathan Rajadurai, Soo-Hwang Teo, Jia Wern Pan. Tumor microbiota associated with immune enrichment in breast tumor [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 6698.
Abstract 6739: Efficacy and toxicity of microbial mimetic mesoporous silica nanoparticles in a mouse model of ovarian cancer
Authors: Medina Lorel Y. , Serda Rita E. , Marwedel Benjamin , Jun Melanie S. , Adogola Josh 
Published: March 2024

Abstract
Ovarian cancer is predominately left undetected and untreated until the later stages of the disease where it becomes incredibly difficult to treat. Preclinical studies demonstrate that immunotherapy can be highly effective. Our lab has been working on an immunotherapy approach to treat women with ovarian cancer that utilizes mesoporous silica nanoparticles(MSN). MSN that present pathogen-associated molecular patterns (PAMPS) are able to significantly reduce tumor burden in mouse models of serous epithelial ovarian cancer when administered by intraperitoneal injection. These microbial mimetic particles are decorated with polyethyleneimine (PEI), CpG oligonucleotide, and monophosphoryl lipid A (MPLA). When in the presence of antigen presenting cells, they bind to Toll-like receptors (TLR) present on the cell surface and within the endosome. To better understand mechanisms underlying their efficacy, we injected fluorescent MSN-PEI-CpG-MPLA (100 or 500 nm) or unmodified MSN into mice with advanced ovarian cancer. The particles, regardless of the presence of TLR-agonists, were rapidly internalized by myeloid cells, with trafficking almost exclusively to immune clusters located in tumor-burdened adipose tissues when administered by intraperitoneal injection. Conversely, intravenous injection of MSN-PEI-CpG-MPLA led to predominate accumulation in liver, with no particles found in tertiary lymphoid clusters 24 hours post injection. Furthermore, unlike intraperitoneal injection, intravenous injection of MSN-PEI-CpG-MPLA was without therapeutic effect. Currently we are studying MSN safety and the impact of administration route and dose on efficacy and cytotoxicity. In summary, MSN, with and without TLR agonists, are trafficked by myeloid cells to tumor-burdened fat-associated lymphoid clusters when administered by intraperitoneal injection. Intraperitoneal injection of TLR-agonist modified MSN effectively reduces tumor burden in mice with ovarian cancer.
Citation Format: Lorel Y. Medina, Rita E. Serda, Benjamin Marwedel, Melanie S. Jun, Josh Adogola. Efficacy and toxicity of microbial mimetic mesoporous silica nanoparticles in a mouse model of ovarian 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 6739.
Abstract 6809: Tumor-associated macrophages promote bladder cancer cell migration and invasion through activation of CCL20-CCR6 axis
Authors: Nakagawa Ryunosuke , Kouji Izumi , Toriumi Ren , Aoyama Shuhei , Kamjima Taiki , Kano Hiroshi , Makino Tomoyuki , Naito Renato , Yaegashi Hiroshi , Nohara Takahiro , Nakata Hiroki , Mizokami Atsushi 
Published: March 2024

Abstract
We focused on Tumor-Associated Macrophages (TAM) and explored its effects on bladder cancer (BC). Co-culturing PMA-treated THP-1 with BC cell lines (UMUC3 and T24) induced THP-1 to develop suppressed CD68 and increased CD206 expression which differentiated into M2-like macrophages. Co-culture of BC with TAM of this M2-like macrophage enhanced the migration and invasive activities of BC, as well as the expression of EMT marker. Human cytokine antibody array of conditioned medium from the co-culture of BC and TAM showed high CCL20, CCL2 and CXCL7. qPCR revealed that these chemokines were mainly derived from TAMs, not BC. Only CCL20 enhanced the migration and invasion of BC and the expression of EMT markers when each of these three recombinant chemokines was administered to BC. Furthermore, inhibiting CCR6, a receptor specific for CCL20, suppressed migration and invasion as expected. In BC, TAMs promote progression and metastasis by secreting CCL20, and inhibition of CCR6 may be one potential therapeutic approach to suppress BC activity.
Citation Format: Ryunosuke Nakagawa, Izumi Kouji, Ren Toriumi, Shuhei Aoyama, Taiki Kamjima, Hiroshi Kano, Tomoyuki Makino, Renato Naito, Hiroshi Yaegashi, Takahiro Nohara, Hiroki Nakata, Atsushi Mizokami. Tumor-associated macrophages promote bladder cancer cell migration and invasion through activation of CCL20-CCR6 axis [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 6809.
Abstract 702: Development of a radioresistant PDX prostate cancer model to evaluate potential radiosensitizing compounds
Authors: Alfsen Maria Zeiler , Thaysen Maria , Nielsen Nikoline , Wick Michael , Piggott Luke , Gnosa Sebastian , Nielsen Carsten Haagen 
Published: March 2024

Abstract
Prostate cancer is the second most common cancer diagnosis worldwide and the fifth leading cause of cancer related death among men. Several treatment strategies are used including the FDA approved 177Lu-vipivotide tetraxetan (177Lu-PSMA-617) for the treatment of prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer. However, not all patients respond to treatment due to tumor intrinsic resistance mechanisms. Therefore, the combination of targeted radionuclide therapy with inhibitors against e.g. DNA damage response, cell cycle progression or cell survival pathways are investigated to enhance the radiosensitivity of the tumor. Current models to study radioresistance in prostate cancer are based on cancer cell lines or cell-line derived xenograft models, but these models do not account for the heterogenous and complex biology of the disease. To overcome this issue, we have developed a radioresistant patient-derived xenograft (PDX) prostate cancer model (ST1273, XenoSTART), that is positive for PSMA. Resistance to radiation was initially established by sequential irradiation of the tumors with external beam radiation. Moreover, the model has proven to be resistant towards treatment with 30 MBq 177Lu-PSMA-617. Utilizing this radioresistant model we are now able to investigate the treatment response of 177Lu-PSMA-617 in combination with different drug inhibitor classes to evaluate their potential radiosensitizing effect. The PARP inhibitor, Olaparib, was administered at 50 mg/kg QDx48 alone or in combination with a single dose of 177Lu-PSMA-617 in radioresistant ST1273 tumor bearing NMRI nude mice. First results showed a prolonging treatment effect of Olaparib given in combination with 177Lu-PSMA-617 compared to 177Lu-PSMA-617 alone. Tumor relapse was observed 29 days after treatment with 177Lu-PSMA-617 alone, whereas it was observed 49 days after combination treatment. Olaparib given alone did not influence tumor growth. To further investigate the mechanism of resistance we are currently investigating the radiosensitizing potential of additional compounds and evaluating the tumors by RNA- and whole-exome- sequencing. Altogether, we successfully established a PSMA positive prostate cancer model resistant to PSMA targeted radionuclide therapy. With this model we are able to investigate the radiosensitizing effect of different drug classes.
Citation Format: Maria Zeiler Alfsen, Maria Thaysen, Nikoline Nielsen, Michael Wick, Luke Piggott, Sebastian Gnosa, Carsten Haagen Nielsen. Development of a radioresistant PDX prostate cancer model to evaluate potential radiosensitizing compounds [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 702.
Abstract 7077: The oncogenic transcription factor ERG has distinct roles and signaling in different prostate cancer cell types
Authors: Rajendran Saranya , Hollenhorst Peter C. 
Published: March 2024

Abstract
ERG is the most common oncogene in prostate cancer, as it is aberrantly expressed in about 50% of cases due to the TMPRSS2/ERG gene rearrangement. ERG is not normally expressed in the adult prostate. The normal function of ERG is confined to hematopoietic stem cells and blood vessels. Aberrant expression of ERG in prostate epithelial cells is oncogenic when combined with mutations that activate the PI3K/AKT signaling pathway. The RAS/MAPK pathway can also regulate ERG function through direct phosphorylation of ERG by ERK. The function of these regulatory events and how they can be exploited to develop therapy for ERG-positive prostate cancer remains unclear. Here we find that ERG expression in prostate epithelial cells with low PI3K/AKT pathway activity drives epithelial to mesenchymal transition and stemness properties. This function requires ERG phosphorylation via a positive feedback loop with the TLR4 signaling pathway, and can be repressed by a TLR4 inhibitor. However, activation of the PI3K/AKT pathway rearranges the ERG cistrome and alters ERG function, where ERG now promotes luminal epithelial differentiation. In the presence of activated AKT, new ERG targets include genes involved in vascular development and ERG phosphorylation is regulated through a positive feedback loop with the VEGF signaling pathway. Despite these differences in cellular differentiation, we find that ERG can promote stemness and tumorigenesis in both AKT-high and AKT-low cellular backgrounds. ERG functions in prostate epithelial cells appear to mirror ERG functions in hematopoietic stem cells and blood vessels. These findings suggest strategies of combinatorial inhibition of ERG function through signaling pathway inhibition.
Citation Format: Saranya Rajendran, Peter C. Hollenhorst. The oncogenic transcription factor ERG has distinct roles and signaling in different prostate cancer cell types [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 7077.
Abstract 7081: Comprehensive investigation of NAT10’s catalytic and non-catalytic functions in cancer cell proliferation
Authors: Raikundalia Sweta Pradeep , Dalhat Mahmood Hassan , Patrasso Emmely A. , Suh Adam , Arango Daniel 
Published: March 2024

Abstract
N-acetyltransferase 10 (NAT10) is emerging as an oncoprotein in multiple cancers including acute myeloid leukemia and liver cancer. In addition, my preliminary studies show that NAT10 is a stress response that promotes the resilience of cancer cells to anti-tumor drugs. However, the underlying mechanisms by which NAT10 promotes cancer growth and drug resistance are unknown. NAT10 is an RNA acetyltransferase, where it acetylates cytidines in rRNA, tRNA, mRNA, and lncRNAs. Our previous work demonstrated that NAT10 promotes translation efficiency and mRNA stability through the acetylation of cytidines in mRNA. However, NAT10 is a multifunctional protein. Besides acetylating RNA, NAT10 also acetylates proteins at lysine residues, has RNA helicase activity, and can serve as a scaffold in ribonucleoprotein complexes. Based on this complexity, it is imperative to elucidate whether NAT10 exerts its oncogenic activity via RNA acetylation, protein acetylation, disruption of RNA structures, or non-catalytic functions. Strikingly, our preliminary results indicate that the acetyltransferase function of NAT10 is dispensable for cell proliferation. To evaluate NAT10’s oncogenic activity unbiasedly, we are now performing a deep mutagenesis scanning (DMS) assay. For this purpose, we generated a library of mutants in hundreds of NAT10 residues. This library was transduced in multiple cell lines from acute myeloid leukemia and liver cancer carrying a PROTAC system, which allow us to deplete NAT10 in a rapid and controlled manner while expressing ectopically thousands of NAT10 mutants. In this conference, I will talk about, my results, how DMS is a powerful tool to delineate the molecular functions of candidate oncoproteins, and the implications of our results for the potential drugging of NAT10 in cancer.
Keywords: Cell proliferation, NAT10, RNA modifications, Deep mutagenesis scanning.
Citation Format: Sweta Pradeep Raikundalia, Mahmood Hassan Dalhat, Emmely A. Patrasso, Adam Suh, Daniel Arango. Comprehensive investigation of NAT10’s catalytic and non-catalytic functions in cancer cell proliferation [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 7081.
Abstract 7151: Targeting metabolic pathway in triple negative breast cancer with a small molecule inhibitor
Authors: Dheeraj Arpit , Marques Fernando Jose , Tailor Dhanir , Bermudez Abel , Grau Benedikt , Pitteri Sharon , Malhotra Sanjay V. 
Published: March 2024

Abstract
Background: Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer, making up 15-20% of diagnosed cases, and has high rates of metastasis and recurrence. Most women with this disease experience a recurrence after curative-intent therapy for early breast cancer, while a smaller proportions are diagnosed with distant metastases initially. Cancer cells are characterized by their reprogramming of glucose metabolism. Cancer cells show increased proliferation along with higher energy and substrate demands. Through our efforts to find effective therapies for TNBC, we have identified CET019, a new small molecule that effectively suppresses the growth of breast cancer cells.
Methods: Cell viability and clonogenic assays were performed on a range of TNBC cells, including MDA-MB-231, MDA-MB-468, SUM159, HCC1395, HCC1806, EMT6, and 4T1. Cell cycle distribution was assessed through flow cytometry. LC-MS/MS analysis was performed on TMT-labeled samples for global proteome profiling. The efficacy of CET019 (30 mg/kg) was tested using tumor and patient derived xenograft studies.
Results: Our studies show that CET019 suppresses the clonogenic potential and growth of various triple-negative breast cancer cells. The CET019 treatment causes cell cycle arrest in TNBC cells at the G2/M phase. Proteomics analysis suggests that CET019 specifically affects metabolic and proteosomal pathways. In vivo studies with CET019 found an inhibition of tumor growth kinetics in the mouse xenograft study with different TNBC models, as compared to the control group. We also observed that CET019 inhibited metastatic lung nodules. The results were further substantiated in three Patient Derived Xenograft (PDX) models.
Conclusion: In summary, our study has identified a novel small molecule candidate CET019 as a promising lead candidate for TNBC treatment, paving the way for further development.“The complete chemical structures of the compounds used will be disclosed at the time of presentation at the meeting.”
Citation Format: Arpit Dheeraj, Fernando Jose Marques, Dhanir Tailor, Abel Bermudez, Benedikt Grau, Sharon Pitteri, Sanjay V. Malhotra. Targeting metabolic pathway in triple negative breast cancer with a small molecule inhibitor [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 7151.
Abstract 7201: Targeting TAZ-TEAD in minimal residual disease enhances the duration of targeted therapy in melanoma models
Authors: Ott Connor A. , Purwin Timothy , Tiago Manoela , Lou Kristine , Chen Pan-Yu , Chowdhury Somaneth , Mersky Glenn , Hacohen Nir , Lamar John , Capparelli Claudia , Bollag Gideon , Aplin Andrew 
Published: March 2024

Abstract
Targeted therapies in cancer are limited by drug tolerance. In melanoma, tolerance to MAPK pathway inhibitors is associated with loss of SOX10 and enhanced YAP1/TAZ-TEAD activity. We show that loss of SOX10 is sufficient to up-regulate a TEAD transcriptional program with a strong dependence on TAZ. We developed a unique gene signature based on the transcriptomic changes following TAZ or YAP1 depletion. Expression of active TAZ was sufficient to mediate tolerance to BRAF inhibitors and MEK inhibitors. In WM983B cells, depletion of TAZ significantly reduced cell growth, whereas YAP1 knockdown resulted in little to no effect. These studies demonstrate that TAZ-TEAD activity plays an important role in melanoma drug tolerance and the development of acquired resistance.
Citation Format: Connor A. Ott, Timothy Purwin, Manoela Tiago, Kristine Lou, Pan-Yu Chen, Somaneth Chowdhury, Glenn Mersky, Nir Hacohen, John Lamar, Claudia Capparelli, Gideon Bollag, Andrew Aplin. Targeting TAZ-TEAD in minimal residual disease enhances the duration of targeted therapy in melanoma models [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 7201.
Abstract 7354: Proteogenomic and metabolomic characterization of acute myeloid leukemia
Authors: Chu Alec , Hsiao Yi , Deng Yamei , Wang Chenwei , Kyle Jennifer , Dou Yongchao , Pino James C. , Posso Camilo , Henry Leanne , Chen Lijun , Li Ginny Xiaohe , Lih Tung-Shing Mamie , Geffen Yifat , Yu Fengchao , Ding Li , Omenn Gil , Kumar Chandan , Dhanasekaran Saravana M. , Traer Elie , Tyner Jeffrey W. , Zhang Hui , Liu Tao , Gosline Sara , Zhang Bing , Chinnaiyan Arul , Nesvizhskii Alexey I. , Cieslik Marcin ,   The CPTAC Consortium
Published: March 2024

Abstract
Acute myeloid leukemia (AML) is a blood malignancy of poor prognosis with marked heterogeneity. To elucidate the underlying mechanisms that drive AML as part of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) effort, we performed comprehensive genomics, transcriptomics, proteomics including multiple post-translational modifications (phosphorylation, acetylation, and glycosylation), metabolomics, and lipidomics characterization of 173 treatment-naïve AML patients. Applying the similarity network fusion method on both transcriptomics and proteomics data, we identified 8 proteogenomic clusters. These clusters recapitulate specific recurrent mutations and established clinical subtypes available within the cohort. We used single-cell RNAseq data as a reference to perform immune component analysis for collected bulk samples. The result reveals that our proteogenomic clustering also captures the variations of AML differentiation hierarchies including CD14+ monocyte-like and GMP-like AML. To assess the complex disease nature of AML, we performed functional analysis for each cluster to reveal interplay between multiple genomic aberrations such as NPM1, FLT3-ITD, DNMT3A mutations, complex chromosomal alterations, and the leukemia cell differentiation. Importantly, the multi-omics analysis performed not only connects previously identified molecular drivers and cell differentiation variations within AML, but also links them with observed cancer metabolomic reprogramming with their drug response implications. Moreover, our study also identified site-specific post-translational modifications previously not known in AML, highlighting the valuable insights and clinical relevance of these newly identified clusters.
Citation Format: Alec Chu, Yi Hsiao, Yamei Deng, Chenwei Wang, Jennifer Kyle, Yongchao Dou, James C. Pino, Camilo Posso, Leanne Henry, Lijun Chen, Ginny Xiaohe Li, Tung-Shing Mamie Lih, Yifat Geffen, Fengchao Yu, Li Ding, Gil Omenn, Chandan Kumar, Saravana M. Dhanasekaran, Elie Traer, Jeffrey W. Tyner, Hui Zhang, Tao Liu, Sara Gosline, Bing Zhang, Arul Chinnaiyan, Alexey I. Nesvizhskii, Marcin Cieslik, The CPTAC Consortium. Proteogenomic and metabolomic characterization of acute myeloid leukemia [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 7354.