bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4795: Social capital and screening mammography rates in the United States
Authors: Huang Tracy , Ekenga Christine 
Published: March 2024

Abstract
Background: Social capital may play a role in screening mammogram utilization by influencing individuals' access to information and providing social support for healthy behaviors. However, few studies have examined associations between community-level social capital and screening mammography use. The purpose of this study was to examine the association between county-level social capital and screening mammography rates in the United States (U.S.).
Methods: We conducted a cross-sectional study of social capital and screening mammography rates across 2,613 U.S. counties for 2014. We obtained county-level data on (1) screening mammography rates for female Medicare enrollees aged 67-69 years and (2) social capital (Penn State Social Capital Index). Multivariable regression models were used to evaluate associations between social capital quartiles and mammography screening rates. Models were adjusted for county-level socioeconomic, demographic, and access to care factors.
Results: Average county-level screening mammography rates were 60.5% ± 8.3% (range 26%-88%). Across all U.S. counties, social capital was associated with county-level mammography rates, after adjusting for covariates (p &lt;0.001). This association did not vary by urban-rural classification. In analyses by region, associations between social capital and screening mammography rates were strongest in the West region (p&lt;0.001).
Conclusions: In this nationwide study, social capital was significantly associated with screening mammography. Our findings suggest that there are regional variations in the association between social capital and mammography rates. The relationship between social capital and cancer screening behaviors warrants further investigation, particularly in the U.S. West.
Citation Format: Tracy Huang, Christine Ekenga. Social capital and screening mammography rates in the United States [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 4795.
Abstract 484: Enhancing therapeutic responses in NSCLC using iron-oxide nanoparticles combined with pharmacological ascorbate
Authors: Singhania Mekhla , Petronek Miachael S. , Pulliam Casey F. , Mapuskar Kranti A. , Zaher Amira , Spitz Douglas R. 
Published: March 2024

Abstract
High dose Vitamin C (pharmacological ascorbate; P-AscH‒ &gt; 20 mM plasma levels) given intravenously (I.V.), has made a remarkable re-emergence as an adjuvant to combined modality approaches in cancer therapy. P-AscH‒ can be readily oxidized in the presence of redox active metals (i.e., P-AscH‒ serves as an iron reducing agent), which can result in increased fluxes of H2O2. This chemical phenomenon allows for the tumor-selective enhancement of chemo-radiation in NSCLC. We hypothesized that enhancing labile Fe2+ in cancer cells using iron-oxide nanoparticles (ferumoxytol, FMX) can increase the effectiveness of P-AscH‒ in enhancing cancer cell sensitivity to chemo-radiation in NSCLC by increasing H2O2 production. To test this hypothesis, we performed clonogenic cell survival assays in-vitro. To test the role of H2O2 in the combined effect of P-AscH‒ and FMX, we developed lentiviral-based doxycycline-inducible overexpression models for catalase, and to determine the changes in Fe, we used fluorescent probes that specifically detect changes in labile Fe2+. Results from these experiments showed FMX enhanced clonogenic cell killing in NSCLC. Furthermore, catalase overexpression inhibited this effect, suggesting that enhanced H2O2 production plays a central role in the additive effect of P-AscH- and FMX. Finally, staining the cells with the fluorescent iron probes showed that FMX enhanced labile Fe2+ in cells treated with P-AscH‒. These studies continue to support the hypothesis that H2O2 plays a significant role in P-AscH‒ toxicity in cancer cells that can be exacerbated using iron oxide nanoparticles. Future studies will test these findings in-vivo using preclinical xenograft models. (supported by P01 CA217797, P30 CA086862, T32 CA078586, and P01 CA244091).
Citation Format: Mekhla Singhania, Miachael S. Petronek, Casey F. Pulliam, Kranti A. Mapuskar, Amira Zaher, Douglas R. Spitz. Enhancing therapeutic responses in NSCLC using iron-oxide nanoparticles combined with pharmacological ascorbate [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 484.
Abstract 4919: AI-enabled hit selection of drug screening on human pancreatic cancer organoids
Authors: Tong Zhisong , Lim Angeline , Meyer Marine , Clapes Maria , Sirenko Oksana , Brandenberg Nathalie 
Published: March 2024

Abstract
Cancer remains one of the leading causes of death in the 21st century. Despite the latest advances in oncology, most cancer patients lack tailored therapeutic approaches with lasting benefit. Measuring the impact of anticancer compounds and their combinations is only possible on ex vivo assays. To this end, patient-derived organoids (PDOs) have been proposed as viable and efficient models for ex vivo testing. PDOs show long-term expansion potential while retaining tumor histopathology as well as cancer gene mutations. However, the translation of organoids in screening applications has so far been hampered by the lack of homogeneity and difficulties in handling and automation. Moreover, organoids are typically randomly distributed across the culture which complicates imaging and images analyses. To overcome these challenges, we set up a compound screening workflow with PDOs using Gri3D platform, comprising plates with micro-cavities suitable for high-throughput and reproducible organoid culture. Based on a standard 96 microtiter plate, each well contains a microwell array patterned in a cell repellent hydrogel. On Gri3D®, organoids are robustly generated in the microwells and are located in the same imaging plane. This greatly facilitates quantitative analyses in high content image-based screens. Furthermore, the pipetting port enables automation of cell seeding, media exchange and compound incubation with liquid-handlers, thus increasing assay reproducibility. In the presented work, we exposed human pancreatic cancer PDOs to a panel of anti-cancer compounds at different doses and followed their response to the drugs using viability dyes Calcein AM (live stain) and Ethidium Homodimer-1 (dead stain) with high-content confocal imaging. Using an AI-based approach, we efficiently detected each single organoid and extracted phenotypic features from all three channels (TL, live stain and dead stain) which correlate with cytotoxicity. The extracted features (more than 100) were first dimensionally reduced to 3 components using either PCA or UMAP, the treatments were then visualized in 3D scatter plots, ranked and clustered using machine learning. The data suggests that the compound treatment Palbociclib 50uM has significant cytotoxicity effects similar to the positive control, which is consistent with the traditional live/dead analysis. The AI approach demonstrates feasibility to perform drug screening in a robust and un-biased data analysis approach.
Citation Format: Zhisong Tong, Angeline Lim, Marine Meyer, Maria Clapes, Oksana Sirenko, Nathalie Brandenberg. AI-enabled hit selection of drug screening on human pancreatic cancer organoids [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 4919.
Abstract 499: Enhancing neoantigen cancer vaccine efficacy with a self-assembling peptide conjugates nanoparticle platform
Authors: Wu Yangfan , Huang Jian-Dong 
Published: March 2024

Abstract
Tumor neoantigens, arising from genomic mutations during cancer cell proliferation, are absent in normal tissues, making them ideal immunotherapy targets. Predicting neoantigen peptide sequences using artificial neural networks (ANNs) like NetMHCpan offers a promising approach to developing personalized peptide cancer vaccines. However, limitations such as low affinity, short half-life, and weak immunogenicity hinder their efficacy. To address these challenges, we propose loading neoantigens into nanoparticles for protection and slow release within the body. We used ANN prediction to determine neoantigen peptide sequences for various cancer cell lines and engineered these peptides by conjugating them with Toll-like receptor 7 agonist (TLR7a) adjuvants, forming a self-assembling peptide conjugates nanoparticle (SPCN) platform. To assess the immunogenicity of the SPCN platform, we conducted enzyme-linked ELISpot assays and evaluated the activation of antigen-presenting cells (APCs) in draining lymph nodes using flow cytometry analysis. The therapeutic efficacy of the SPCN platform was determined by monitoring tumor growth curves in mouse models. The SPCN platform demonstrated broad applicability, carrying different neoantigens in vivo, resulting in robust and safe systemic anti-tumor responses. The SPCN enhanced immunogenicity, stimulating splenocytes to produce more interferon gamma and facilitating efficient absorption by antigen-presenting cells (APCs). Moreover, SPCNs loaded with neoantigens targeted different cancer models, including B16OVA, MB49, and RIL175. In conclusion, our self-assembling peptide conjugates nanoparticle platform enhances APC activation and neoantigen immunogenicity, leading to improved anti-tumor efficacy, offering valuable insights for developing synthetic peptide cancer vaccines.
Citation Format: Yangfan Wu, Jian-Dong Huang. Enhancing neoantigen cancer vaccine efficacy with a self-assembling peptide conjugates nanoparticle platform [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 499.
Abstract 5009: Deciphering anticancer mechanisms of oncolytic virus-loaded stem cells
Authors: Hammad Mohamed , Seth Arun , Yuan Yate-Ching , Ngai Hoi Wa , Mooney Rachael , Lara Jacqueline , Kang Yunyi , Minev Ivelina , Nguyen Duong Hoang , Minev Boris , Santidrian Antonio , Aboody Karen 
Published: March 2024

Abstract
Background: Oncolytic viruses (OVs) selectively trap, replicate, and eradicate tumor cells without endangering healthy cells. However, any virus that enters the body will be found and rendered inactive by our immune system. Therefore, cancer-killing viruses don't function properly when given by themselves. Loading therapeutic viruses into stem cells is a promising solution since they shield the OVs from the immune system until they reach tumor cells and eventually destroy them. Stem cells are potent immunomodulators and, apart from protecting and delivering the cancer-killing viruses may release additional cell factors that may regulate tumor microenvironment favoring the effect of the therapy. In this study, we analyze these factors secreted by clinically relevant stem cells loaded with oncolytic viruses CLD-101 (Neuronova platform) and CLD-201 (Supernova platform)
Method: In our studies, we loaded neural stem cell line (NSCs) with tumor-selective oncolytic adenovirus CRAD-s-PK7 (CLD-101) and adipose-derived stem cells (AD-MSC) with tumor-selective oncolytic adenovirus vaccinia virus CAL1 (CLD-201), and studied their secretome transcriptomic and proteomic profile.
Results: The transcriptomic analysis demonstrated that immunomodulatory cytokines, chemokines, and their receptors are induced after three and twenty-four hours of OV infection. The proteomic analysis of the virus-loaded stem cells revealed a notable distinction from the naive stem cells indicating a potential immunotherapeutic role of the stem cells in addition to the delivery and protection of the OVs.
Conclusions: Our findings suggest that the enhanced therapeutic efficacy of stem cells loaded with OV is, at least partially because of qualitative and quantitative alterations in stem cells' secretome (including immunostimulatory cytokines and chemokines), These findings advance our knowledge of the molecular mechanisms underlying the immunostimulatory role of OV-loaded stem cells and specifically help to understand the mechanism of action of the promising clinical immunotherapies CLD-101 and CLD-201.
Citation Format: Mohamed Hammad, Arun Seth, Yate-Ching Yuan, Hoi Wa Ngai, Rachael Mooney, Jacqueline Lara, Yunyi Kang, Ivelina Minev, Duong Hoang Nguyen, Boris Minev, Antonio Santidrian, Karen Aboody. Deciphering anticancer mechanisms of oncolytic virus-loaded stem cells [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 5009.
Abstract 5052: Novel drug resistance mechanisms and drug targets in BRAF mutated peritoneal metastasis from colorectal cancer
Authors: Lund-Andersen Christin , Torgunrud Annette , Kanduri Chakravarthi , Dagenborg Vegar J. , Frøysnes Ida S. , Larsen Mette M. , Davidson Ben , Larsen Stein , Flatmark Kjersti 
Published: March 2024

Abstract
Objective: Patients with peritoneal metastasis (PM) from colorectal cancer (CRC) have inferior prognosis and respond poorly to chemotherapy compared to other metastatic locations. This study aims to identify the molecular explanation for the observed clinical behavior and suggest novel treatment strategies in PM-CRC.
Design: Tumor samples from a Norwegian national cohort of 230 patients undergoing surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C (MMC) for PM-CRC were subjected to targeted DNA sequencing, and associations between molecular findings and clinical data were analyzed. mRNA sequencing was conducted on a subset of thirty samples to compare gene expression in tumors harboring mutations in the BRAF or KRAS oncogenes and wild-type tumors.
Results: Almost one-third of the patients had mutations in the BRAF oncogene, which were associated with RNF43/R-Spondin aberrations and low expression of negative Wnt regulators (ligand dependent Wnt activation). This molecular profile, with high abundance in PM, could be an underlying mechanism promoting aggressive tumor biology that facilitates metastasis to the peritoneal cavity, and could contribute to the observed poor overall survival of this patient subgroup. BRAF mutations were also associated with gene expression changes in transport solute carrier proteins and drug metabolism enzymes that could influence the efficacy of MMC and irinotecan, commonly used in PM-CRC treatment. BRAF-mutated tumors exhibited increased expression of BTN immune checkpoint molecules, and targeting these checkpoints in addition to ligand dependent Wnt activation could be two novel targeted therapy approaches.
Conclusion: BRAF mutations were associated with particularly poor survival in this cohort, possibly related to altered drug transport and metabolism conferring resistance to MMC and irinotecan. Two potential novel therapeutic approaches were identified, suggesting specific targeting of BTN immune checkpoint molecules and the use of inhibitors to target ligand-dependent Wnt activation.
Citation Format: Christin Lund-Andersen, Annette Torgunrud, Chakravarthi Kanduri, Vegar J. Dagenborg, Ida S. Frøysnes, Mette M. Larsen, Ben Davidson, Stein Larsen, Kjersti Flatmark. Novel drug resistance mechanisms and drug targets in BRAF mutated peritoneal metastasis from 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 5052.
Abstract 5062: Evaluation of genetic mutations in non-small cell lung cancer patients
Authors: Rothstein Miles , Broughton Phillip , Markalunas Ella , Funkhouser Avery , Allen Lorie , Martin Julie , Edenfield W. Jeffery , Blenda Anna V. 
Published: March 2024

Abstract
Lung cancers represent the second most common cancer and Non-Small Cell Lung Cancer (NSCLC) constitutes 80-85% of all lung cancers. Genes within several cellular pathways have been previously evaluated for their clinical impact in NSCLC. In this investigation, we evaluate genetic mutations found in 50 cancer-critical genes implicated in the signaling pathways RTK/RAS/MAP, TGFβ, PI3K, Wnt, GPCR, p53, JAK/STAT, Notch, and the cell cycle pathway. Some of these mutations have not yet been described or have not been described in NSCLC. The intent of our study is to evaluate these mutations and allow further research into their impact, specifically highlighting mutations that are involved in clinically important pathways.
We evaluated mutations found in 59 NSCLC patients at the Prisma Health Cancer Institute. These mutations are part of 2,800 COSMIC (Catalogue of Somatic Mutations in Cancer) hotspot mutations in 50 cancer-critical genes. Each mutation was investigated further using the ClinVar database to identify whether it had been described in NSCLC or other cancers/conditions, its genetic consequence, pathogenesis, possible variations, and origin.
A total of 73 unique mutations in 59 NSCLC patients were evaluated. Of the 73 mutations, 17 had not been described at all, 40 had been described in other cancers/conditions, and 16 had been previously described in NSCLC. The known mutations’ effects in other cancers/conditions were categorized as pathogenic, likely pathogenic, likely benign, benign, or uncertain. Novel mutations were found in genes that provide a druggable target, help predict treatment response, are under investigation for their ability to predict treatment response or confer additional clinical utility.
Medical management of cancer has benefitted greatly from studies of genetic mutations. Most mutations identified in our patient population had not been described in NSCLC, and a smaller number of those had not been described at all. Further elucidation of these mutations may lead to additional discoveries relevant to NSCLC prognostication and treatment.
Citation Format: Miles Rothstein, Phillip Broughton, Ella Markalunas, Avery Funkhouser, Lorie Allen, Julie Martin, W. Jeffery Edenfield, Anna V. Blenda. Evaluation of genetic mutations in non-small cell lung cancer patients [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 5062.
Abstract 507: HLS-22001 induces G2/M cell cycle arrest and apoptotic cell death via tubulin depolymerization in colon cancer
Authors: Ahn Chi-hyun , Jang Gyu-beom , Kim Chunhwa , Lee Junho , Kim Taewon , Yang Youngeun , Cho Eunji , Kim Minchae , Kim Yun-tai , Han Yong-Hae , Kang Heebum 
Published: March 2024

Abstract
Colorectal cancer (CRC) is one of the main malignant tumors and among the leading cause of death in cancer patients worldwide considering that recurrence and chemotherapeutic drug resistance are highly common in the advanced stage of CRC. Mutations in KRAS and BRAF occur frequently in colorectal cancers, and abnormal cell cycles caused by these mutations affect tumor progression and metastasis. Accordingly, inhibition of cell cycle has been a potential target for colorectal cancers and therefore, we have developed a new lead compound, HLS-22001.
Our studies confirmed that HLS-22001 inhibited the proliferation of several cancer cells and significantly induced G2/M arrest and apoptosis of colon cancer cells and chemotherapy resistant colon cancer cells. The docking model studies showed that HLS-22001 was expected to bind to the colchicine binding site of beta-tubulin, and in fact, as a tubulin inhibitor, it had the effect of inhibiting tubulin dimerization and polymerization in the microtubule dynamics. Consistently, in xenograft mouse model, oral administration of HLS-22001 significantly suppressed tumor weight and volume without acute toxicity in mice.
Collectively, these results suggest further development of HLS-22001 as a novel and promising oral drug for colorectal cancer.
Citation Format: Chi-hyun Ahn, Gyu-beom Jang, Chunhwa Kim, Junho Lee, Taewon Kim, Youngeun Yang, Eunji Cho, Minchae Kim, Yun-tai Kim, Yong-Hae Han, Heebum Kang. HLS-22001 induces G2/M cell cycle arrest and apoptotic cell death via tubulin depolymerization in colon 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 507.
Abstract 5082: Novel TSHR CAR T therapy for targeting oncocytic carcinoma
Authors: Gleba Justyna J. , Alasonyalilar-Demirer Aylin , Pawlush Matthew , Manriquez-Roman Claudia , Siegler Elizabeth L. , Smallridge Robert C. , Zubair Abba , Tun Han W. , Kenderian Saad S. , Copland John A. 
Published: March 2024

Abstract
Oncocytic carcinoma (Hurthle cell carcinoma) has the highest incidence of metastasis among the differentiated thyroid cancers. Metastatic disease is reported at the initial diagnosis in 10-20% of patients and 34% overall. Thyroid-stimulating hormone receptor (TSHR) expression is limited to the thyroid gland. It is abundantly expressed on thyroid tumor cells, making TSHR a compelling target for advanced thyroid cancer diagnostics and therapeutics. We developed a potent anticancer strategy for treating oncocytic carcinoma using a novel thyroid hormone stimulating receptor (TSHR)- targeted (chimeric antigen receptor) CAR T cell therapy. TSHR CAR T was generated by transducing T cells derived from healthy donors. In vitro effector functions (cytotoxicity, proliferation, degranulation) were tested in TSHR+ tumor models, and subsequent in vivo studies using NSG mice were performed to assess anti-tumor activity efficacy. We observed strong anti-tumor activity against metastatic oncocytic carcinoma cell line XCT.UC1 using the TSHR CAR T therapy in vivo. Re-challenging treated mice with XCT.UC1 cells reactivated TSHR CART cells with enhanced proliferation and complete suppression of tumor growth of the newly injected tumor cells. Our work represents a promising strategy to improve treatment outcomes of patients with metastatic oncocytic carcinoma that may provide a durable response.
Citation Format: Justyna J. Gleba, Aylin Alasonyalilar-Demirer, Matthew Pawlush, Claudia Manriquez-Roman, Elizabeth L. Siegler, Robert C. Smallridge, Abba Zubair, Han W. Tun, Saad S. Kenderian, John A. Copland. Novel TSHR CAR T therapy for targeting oncocytic 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 5082.