bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4822: Disparities in receiving non-surgical therapy impact outcomes in non-metastatic gastric cancer in Louisiana
Authors: Hartupee Conner D. , Maupin Kyla , Danos Denise M. , Moaven Omeed 
Published: March 2024

Abstract
Background: Given the history of evolving medical therapies and advancements in cancer treatments over the last decades, resectable gastric cancer has presented multiple strategies for care. Previous literature indicates historically decreased use of multimodal therapies in minority populations. This study aims to evaluate Louisiana patient populations for rates of definitive treatment, inequities in access to care, and evaluating its impact on the outcomes of minorities and underserved population.
Methods: Patients with non-metastatic primary invasive gastric cancer, with T2-4 or any T status with positive lymph nodes, were identified in the Louisiana Tumor Registry using ICD-O codes and AJCC staging system. Receipt of non-surgical therapy was modeled using logistic regression. Overall survival (OS) was modeled using a Cox proportional hazards model.
Results: The study included 561 patients, of which 37.6% (n=211) did not receive surgical treatment and 16.2% (n=91) did not receive non-surgical therapy. A subset of the cohort received no definitive treatment, (6.8%, n=38). In a demographic only multivariable model, adjusting for age, sex, and race, age 70 and over [OR (95%CI) =0.18 (0.08-0.42), p&lt;0.001] and female sex [OR (95%CI) =0.48 (0.28-0.85), p=0.011] was associated with decreased rates of non-surgical therapy. Black [OR (95%CI) = 0.54 (0.31-0.93), p=0.027] and Hispanic [OR (95%CI) = 0.38 (0.13-1.08), p=0.070] race was associated with decreased receipt of non-surgical therapies. However, after adjusting for domestic partner, insurance status, rurality, area poverty, and surgery status, racial disparities were no longer significant compared to whites: Black [OR (95% CI) = 0.59 (0.33-1.06), p=0.075]; Hispanic [OR (95% CI) = 0.52 (0.17-1.66), p=0.272]. In multivariable analyses, receipt of surgery [HR (95% CI) = 0.3 (0.23 - 0.38), p&lt;0.001) and any non-surgical therapy [HR (95% CI) = 0.43 (0.31 - 0.60), p&lt;0.001) were associated with increased overall survival.
Conclusion: A significant number of patients did not receive all modalities of the multidisciplinary treatment that is recommended for patients with non-metastatic gastric adenocarcinoma. Black patients and females are less likely to receive non-surgical modalities for gastric cancer in Louisiana, which is, at least, partially driven by socioeconomic determinants. Identifying patients with these risk factors is a crucial step in allocating resources to increase access the care and improve outcomes.
Citation Format: Conner D. Hartupee, Kyla Maupin, Denise M. Danos, Omeed Moaven. Disparities in receiving non-surgical therapy impact outcomes in non-metastatic gastric cancer in Louisiana [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 4822.
Abstract 4831: Racialized economic segregation and disparities in late-stage diagnosis, treatment and mortality among patients with non-small cell lung cancer
Authors: Shrestha Pratibha , Lian Min , Liu Ying 
Published: March 2024

Abstract
Importance: Little is known about the impact of residential segregation on early detection, treatment, and prognosis among patients with non-small cell lung cancer (NSCLC), a predominant type of lung cancers.
Objective: To examine the associations of racialized economic segregation with the risks of late-stage diagnosis, non-adherence to guideline-recommended treatment, and mortality among non-Hispanic White (NHW) patients and non-Hispanic Black (NHB) patients with NSCLC.
Methods: This population-based retrospective cohort study included patients with NSCLC as a first primary malignancy diagnosed at age 20 and older between January 2007 and December 2015, followed through December 2016, and identified from the Surveillance, Epidemiology, and End Results (SEER) dataset released in April 2019. County-level racialized economic segregation was estimated using the Index of Concentration at the Extremes (ICE). We used multilevel logistic regression and multilevel Cox regression accounting for county-level clustering to estimate odds ratios (ORs) for late-stage diagnosis and non-adherence to guideline-recommended treatment, and hazard ratios (HRs) for overall mortality and lung cancer-specific mortality.
Results: Of 203, 441 patients, 85.8% were NHW and 14.2% were NHB. Compared with patients living in the most privileged (lowest ICE quintile―segregated, high-income NHW) counties, patients living in the least privileged (highest ICE quintile―segregated, low-income NHB) counties had higher risks of late-stage diagnosis (OR=1.09, 95% CI: 1.02-1.16; Ptrend &lt;.001), non-adherence to guideline-recommended treatment (OR=1.28, 95% CI: 1.16-1.41; Ptrend &lt;.0001), lung cancer-specific mortality (HR=1.10, 95% CI: 1.07-1.14; Ptrend &lt;.0001), and overall mortality (HR=1.12, 95% CI: 1.09-1.16; Ptrend &lt;.0001). The association of segregation with treatment underutilization was stronger in NHW patients than NHB patients (Pinteraction =0.02). There was no significant difference in the segregation-related risk of late-stage diagnosis, lung cancer-specific mortality, or overall mortality between NHW and NHB patients.
Conclusions: Living in segregated, low-income NHB counties was associated with increased risks of late-stage diagnosis, suboptimal treatment, and mortality among patients with NSCLC. Future research should investigate contributors to the adverse impact of residential segregation on lung cancer care and outcomes.
Citation Format: Pratibha Shrestha, Min Lian, Ying Liu. Racialized economic segregation and disparities in late-stage diagnosis, treatment and mortality among patients with non-small cell lung 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 4831.
Abstract 486: Paclitaxel nanoformulation attenuates pancreatic tumor desmoplasia and alter tumor immune responses
Authors: Kashyap Vivek K. , Darkwah Godwin P. , Chauhan Neeraj , Sikander Mohammed , Ghali Eswara N. , Kolli Meghana , Hafeez Bilal B. , Yallapu Murali M. , Chauhan Subhash C. 
Published: March 2024

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer with a 5-year survival rate of less than 13% due to the lack of effective diagnostic/therapeutic modalities. Paclitaxel (PTX) has been tested in pancreatic cancer (PanCa) therapy with marginally better clinical outcomes, but remains limited by its poor hemocompatibility, biodistribution, and intracellular accumulation in tumor cells. Gemcitabine (GEM) is the most effective therapy for PanCa. However, it shows only a marginal survival benefit of 6 months. The poor therapy response is attributed to high desmoplasia, unfavorable tumor microenvironment (TME), and excessive recruitment of immune suppressive cells. We have recently engineered a multi-layered Pluronic F127 and polyvinyl alcohol stabilized and poly-L-lysine coated paclitaxel loaded poly(lactic-co-glycolic acid) nanoparticle formulation (PPNPs), which effectively inhibits pancreatic tumor. In this study, we demonstrate that PPNPs effectively sensitize tumor cells to GEM via attenuation of tumor desmoplasia. Our findings also show that PPNPs synergize GEM therapy response in cell lines and in vivo mouse models. Mechanistically, PPNPs target the TME via inhibition of the sonic hedgehog (SHH) pathway and other oncogenic signaling axis that inhibits bidirectional tumor-stromal cell interaction as determined by qPCR and Western blot analyses. In addition, PPNPs effectively target tumor-associated macrophages (TAM) by repolarizing M2 into M1 phenotype via inhibiting expression of M2 markers and an increase in M1 markers in mouse macrophage cell line RAW264.7. M2 polarization of RAW264.7 cells were induced by culture with IL-4 (20 ng/mL) in the presence of PPNPs or vehicle control. Furthermore, PPNPs effectively increase phagocytic capacity in murine macrophages as determined by phagocytosis assay (Vybrant Phagocytosis Assay Kit). In conclusion, we observed that our novel PPNP nano formulation effectively targets TME, and facilitates GEM uptake by inhibiting the activation of SHH signaling and reprograming the tumor immune surveillance mechanisms. This study suggests that PPNPs have great potential for future clinical use in management of pancreatic cancer.
Citation Format: Vivek K. Kashyap, Godwin P. Darkwah, Neeraj Chauhan, Mohammed Sikander, Eswara N. Ghali, Meghana Kolli, Bilal B. Hafeez, Murali M. Yallapu, Subhash C. Chauhan. Paclitaxel nanoformulation attenuates pancreatic tumor desmoplasia and alter tumor immune responses [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 486.
Abstract 4879: Delineating lymphocyte aggregates from tertiary lymphoid structures using spatial transcriptomics
Authors: Krull Jordan , Byappanahalli Anjali , Jiang Yi , Gunderson Andrew , Ma Qin 
Published: March 2024

Abstract
Tertiary Lymphoid Structures (TLSs) are ectopic lymphoid structures that form in chronically inflamed non-lymphoid tissue. The presence of TLSs in tumors is largely associated with favorable outcomes among patients and also exhibit positive associations with response to immune checkpoint blockade. Although mainly comprised of lymphocytes (B cells and T cells), they are considered a separate entity from lymphocyte aggregates within tissue. Lymphocyte aggregates are fairly routine to identify in H&E stained tissue sections, but delineating TLSs from simple lymphocyte aggregates is subjective and not clearly defined. Additionally, the definition of TLSs is only recently being elucidated, so a clear molecular definition of both TLSs and lymphocyte aggregates is needed. To address this problem, we leveraged open-source spatial transcriptomics (ST) data from 17 samples across 7 cancer types. High resolution H&E images were manually evaluated for lymphocyte aggregates by identifying dense pockets of lymphocytic-appearing nuclei. Suspected aggregates were detected in 10 of 17 samples. We then applied a visium spot-level signature scoring method for 4 well published TLS signatures. Of the spots identified, 62% had enhanced signature expression for at least 2 of the signatures, although most of the incorrect annotations came from the lone gastric cancer sample. Differential expression between a TLS-sig- suspected lymphoid aggregate and a TLS-sig+ region not identified by H&E enriched primarily for B cell identity genes, suggesting B-cell-rich TLSs may not always appear as lymphoid aggregates in histology. [AG1] Strikingly, ST revealed strongly positive enhancements in the TLS signatures, where no annotations were made, and no obvious lymphoid aggregation was present, suggesting manual annotation from H&E is inadequate for identifying TLSs. Together, these results demonstrate that literature derived TLS signatures can correctly identify lymphoid aggregates as TLSs and that cellular and molecular differences between standard lymphoid aggregates and TLSs may be smaller than is currently accepted.
Citation Format: Jordan Krull, Anjali Byappanahalli, Yi Jiang, Andrew Gunderson, Qin Ma. Delineating lymphocyte aggregates from tertiary lymphoid structures using spatial transcriptomics [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 4879.
Abstract 4896: A high throughput method of identifying cells with increased genomic content across diverse cancer tissues
Authors: Nair Shilpa Priyadarsini , Pienta Kenneth J. , Amend Sarah R. 
Published: March 2024

Abstract
Cancer cells with increased genomic content have been associated with recurrence and poor patient outcomes. The current manual identification of these rare cells by pathologists is time-consuming and labor intensive, given their scarcity within tissue samples. This study introduces a robust methodology for the automated identification of cancer cells with increased genomic content within prostate cancer tissues. Leveraging Qupath software integrated with the Stardist extension, our approach combines precise nuclear segmentation with threshold setting using a Python script. This methodology enables the specific identification of noncancerous small cells, cancerous cells, and those exhibiting genomic content significantly surpassing the average cancer cell (3x to 5x), complemented by thresholds based on hematoxylin intensity for enhanced result accuracy. Thus, our methodology offers an efficient solution to streamline the identification processes for these challenging cells.
We have extensively validated our method across diverse models, including animal and human models, transgenic and subcutaneous models, and Human Tissue Microarrays (TMAs), to identify cancer cells with increased genomic content. The rarity of these cells within tissue samples underscores the practical significance of our research, providing a solution to the current difficulties faced by researchers and clinicians in their identification.
The integration of this methodology aims to improve efficiency in cancer tissue analysis. Ongoing efforts are directed towards the evaluation of this high-throughput methodology using animal models and TMAs with known outcomes, further substantiating its applicability and potential clinical relevance.
Citation Format: Shilpa Priyadarsini Nair, Kenneth J. Pienta, Sarah R. Amend. A high throughput method of identifying cells with increased genomic content across diverse cancer tissues [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 4896.
Abstract 4901: High-resolution spatial transcriptomics identifies candidate genes facilitating perineural invasion
Authors: Olgun Deniz Guney , Wang Peter L. , Zhao Ryan , Gong Dennis H. , Hwang William L. 
Published: March 2024

Abstract
Perineural invasion (PNI), or the invasion of cancer to the space surrounding nerves, is associated with poor prognosis, but the underlying molecular factors that drive its initiation and progression are poorly understood. To explore this systematically, we applied a 6000-plex spatial transcriptomic panel with subcellular resolution to curated microarrays from 5 pancreatic ductal adenocarcinoma (PDAC) patients spanning different stages of tumor-nerve involvement. With this preliminary cohort, we explored malignant cell signatures associated with invasion and adaptation to the intraneural environment. Strikingly, we observed enrichment of a classical-like malignant transcriptional program marked by genes involved in glucose and lipid metabolism in nerve-invading malignant cells. Despite the known association of chemoresistance with serine dependence, these cells also exhibited upregulation of genes involved in serine biosynthesis, suggesting that intraneural invasion may offer an orthogonal path of treatment evasion. Overall, our findings indicate that nerve-invasive cancer cells adopt a unique transcriptomic signature within the neuronal microenvironment. Further studies will aim to uncover the relevance of these signatures to survival within the nerve environment and treatment resistance.
Citation Format: Deniz Guney Olgun, Peter L. Wang, Ryan Zhao, Dennis H. Gong, William L. Hwang. High-resolution spatial transcriptomics identifies candidate genes facilitating perineural invasion [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 4901.
Abstract 492: Investigating solute carrier SLC46A3 to enhance nanotherapeutic delivery for cancer
Authors: Kenny-Serrano Julianna , Nelson Elizabeth B. , Covarrubias Gil , Nabar Namita , Straehla Joelle , Gupta Aanchal , Boehnke Natalie , Hammond Paula 
Published: March 2024

Abstract
BACKGROUND: Nanoparticle therapeutics have multifaceted potential to improve efficacy and decrease toxicity of cancer treatments. Nanotherapeutics can encapsulate a range of cargos and have tunable surface chemistry that can enhance drug delivery to tumors. Cellular features also play a role in successful drug delivery, and predictive biomarkers may improve patient selection for clinical trials. In previous work, we identified SLC46A3, a poorly characterized lysosomal solute carrier, as a strong negative regulator of lipid-based nanoparticle uptake across many cancer models. We hypothesize that the expression of SLC46A3 will act as a predictive biomarker for therapeutic nanoparticles.
METHODS: To test this hypothesis, we used two engineered model systems to probe the relationship between SLC46A3 expression and therapeutic response: lentiviral overexpression in a natively low-expressing melanoma model and genetic deactivation in a natively high-expressing breast cancer model. A library of FDA-approved and experimental therapeutic nanoparticles were screened in both models under a range of conditions. Liposomal formulations of chemotherapeutics were included with high and low surface functionalization of polyethylene glycol to investigate the impact of this ubiquitous ‘stealth’ polymer on our biomarker of interest. Solid lipid nanoparticles with nucleic acid cargo were also included. Orthogonal methods were used to probe these interactions and the therapeutic efficacy of nanotherapeutics, including pulsed dosing viability assays and label-free live-cell imaging.
RESULTS: We found that SLC46A3 expression is a class-specific biomarker of lipid-based nanoparticle uptake and is predictive of distinctive patterns of response to therapy-loaded nanoparticles in both formulation and time-dependent manners. Additionally, we present a new technology for long-term, live cell imaging of nanoparticle uptake and trafficking that can discriminate mechanisms of cytotoxicity, accelerating the study of nano-bio interactions. These findings highlight a promising approach for the functional validation of nanoparticle-specific biomarkers using clinically relevant formulations that have the potential for rapid repurposing.
Citation Format: Julianna Kenny-Serrano, Elizabeth B. Nelson, Gil Covarrubias, Namita Nabar, Joelle Straehla, Aanchal Gupta, Natalie Boehnke, Paula Hammond. Investigating solute carrier SLC46A3 to enhance nanotherapeutic delivery for 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 492.
Abstract 494: Fluorescent carbon dots: A novel bioimaging tool to reveal the mechanism of action of anticancer drugs in cells
Authors: Clermont-Paquette Adryanne 
Published: March 2024

Abstract
The mechanism of action of many cancer drugs at the subcellular level remains unknown. Yet, this knowledge could be critical in driving structure-activity-relationship studies to improve their efficacy and selectivity. To gain a deeper understanding of the mechanisms governing the action of anticancer drugs within cells, we are developing an innovative methodology to visualize drug interactions. Carbon dots (CDs) are carbon-based nanoparticles, distinguished not only by their remarkable optical properties but also by their minimal cytotoxicity, rendering them highly suitable for bioimaging applications. We recently found that amine-passivated CDs with a negative surface charge and amphiphilic properties were enriched in the cytosol of cultured human cells. These CDs emit fluorescence in the blue spectra with high quantum yields and are not cytotoxic. Importantly, their surface is decorated with amine functional groups that can be used for coupling to polyethylene glycol to create a linker that can be covalently attached to drugs of interest. First, we are covalently linking amine-passivated CDs to Doxorubicin (Dox), a well-known anti-cancer drug that intercalates DNA and also has fluorescence properties that differ from the CDs. This will permit us to monitor and validate the conjugation of Dox to CDs, their cellular uptake and localization. The next step will be to use this approach to reveal the cellular mechanism of action of novel anticancer drugs. Specifically, our group has rationally designed thienoisoquinoline compounds with selectivity and high efficacy for triple negative breast cancer cells. In vitro they disrupt microtubule polymerization in the nanomolar range. However, in cells they cause mitotic arrest and spindle phenotypes that are distinct from colchicine, another microtubule-targeting drug. Our approach will reveal if these compounds target the centrosomes and/or microtubules and if this varies with cell types. This innovative approach could yield profound insights into the intracellular mechanisms of anticancer drugs to facilitate structure-activity-relationship studies, to improve their efficacy and selectivity for drug development.
Citation Format: Adryanne Clermont-Paquette. Fluorescent carbon dots: A novel bioimaging tool to reveal the mechanism of action of anticancer drugs in 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 494.