bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2614: A deep learning model-based lung cancer risk assessment for incidental pulmonary nodules
Authors: Yuan Pengyu , He Tiancheng , Nguyen Hien , Wong Stephen T. 
Published: July 2021

Abstract
Lung cancer is the leading cause of cancer death among both men and women. The solitary pulmonary nodule (SPN) is frequently seen on radiographs and computed tomography (CT) and often provokes additional clinical and imaging activities as an SPN alerts possible early stage lung cancer. However, reliable diagnosis of malignant lung nodules in the workup of SPN is challenging, making it difficult for early stage cancer management to avoid morbidity due to malignant cancer, patient distress, and increased costs caused by more invasive and unwarranted procedures for benign cases. We developed a deep learning model based on convolutional neural networks (CNNs) to predict lung cancer risk for incidental SPN. The model can help better management of incidental lung cancer by providing a reliable characterization of SPNs. Deep learning models currently are applied to nodule detection in low-dose CT scans of lung cancer screening for at-risk population. Our work aims to investigate whether deep learning can differentiate benign from malignant incidental SPN during normal dose CT exams, where the number of patients with SPN is an order more than that of lung screening population. We collected an incidental SPN dataset containing 139 CT scans to generate the nodule malignancy prediction model using 3D CNN. This dataset was collected from either contrast or non-contrast CT scans with regular doses. All 139 patients went through surgeries to remove the tumors. CT images were collected within one year before the surgery. 90 cases are malignant and the rest are benign. Ground truth labels were obtained from biopsies. Data were preprocessed by resampling, normalization, and cropping to unique volume around the SPN. The radiologists annotated the SPN location. Since the two nodule classes are imbalanced, we did online data augmentation to increase the variety of lung nodule images and balance the two classes. We used 80% of the data for training and 20% for testing. The deep learning structure adapted is a 3D Resnet with 68 layers and 33M parameters. The area under the receiving operating characteristics curve (AUC) of the prediction result was 0.81 while the accuracy was 79.6%. Applying GradCam to visualize important regions in CT scans contributing to the final predictions, we found that our trained ResNet model focuses on meaningful areas in lung nodules and detects malignant SPNs in most cases. Our preliminary results shows the feasibility of using deep learning to predict incidental lung nodules and improve diagnostic speed and accuracy.
Citation Format: Pengyu Yuan, Tiancheng He, Hien Nguyen, Stephen T. Wong. A deep learning model-based lung cancer risk assessment for incidental pulmonary nodules [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2614.
Abstract 2632: Fostering engagement in biobanking and research through the NCI Cancer Moonshot Biobank patient and provider engagement website
Authors: Casas-Silva Esmeralda , Agrawal Lokesh , Ellis Helena J. , Gopalakrishnan Veena , Guan Ping , Jensen Mark , Madero Natalie , McDermott Sean , McLean Jeffrey , Rao Abhi , Suh James , Wanyiri Jane , Weil Carol J. , Williams Mickey , Moore Helen M. 
Published: July 2021

Abstract
The National Cancer Institute's (NCI) Cancer Moonshot Biobank (the Biobank) aims to accelerate cancer research on treatment resistance and sensitivity through collection of longitudinal biospecimens and health data donated by participants diagnosed with late-stage cancer and receiving standard of care therapy at participating NCI Community Oncology Research Program (NCORP) sites.
Participant and provider engagement are a central tenet of the Biobank. We therefore created an innovative website to interface directly with participants and providers and to meet our engagement goals of returning value to stakeholders, operating with transparency, maintaining bi-directional communication, and enrolling a diverse population that represents the U.S. including racial/ethnic minorities, rural populations and others that are historically underrepresented in clinical research. The Biobank engagement website has several features designed to provide return of value to stakeholders. This includes clear information about the program, transparency about how biospecimens and data will be used in research, and the ability to access and download documents such as clinical biomarker tests and signed consent forms. The website also includes project updates, participant and provider resources, and educational material.
The Cancer Moonshot Biobank Participant and Provider Engagement website serves as an important interface between the Biobank and its stakeholders. Its ultimate aim is to facilitate project engagement and return value to participants and providers.
Citation Format: Esmeralda Casas-Silva, Lokesh Agrawal, Helena J. Ellis, Veena Gopalakrishnan, Ping Guan, Mark Jensen, Natalie Madero, Sean McDermott, Jeffrey McLean, Abhi Rao, James Suh, Jane Wanyiri, Carol J. Weil, Mickey Williams, Helen M. Moore. Fostering engagement in biobanking and research through the NCI Cancer Moonshot Biobank patient and provider engagement website [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2632.
Abstract 2671: SMAD4 as a potential gatekeeper for genomic instability and mTOR-mediated tumorigenesis in esophageal adenocarcinoma
Authors: Milne Julia V. , Gotovac Jovana R. , Fujihara Kenji M. , Duong Cuong P. , Phillips Wayne A. , Clemons Nicholas J. 
Published: July 2021

Abstract
Esophageal cancer is the 8th most common cancer worldwide and has the 6th highest mortality rate of all cancers. The 5-year survival rate following esophageal adenocarcinoma (EAC) diagnosis is dismal at less than 15 percent, indicating a dire need for improved therapeutic strategies and early detection. EAC develops stepwise following exposure to chronic gastric reflux: From pre-malignant Barrett's metaplasia, through stages of low- and high-grade dysplasia until developing into invasive cancer. Mutation or loss of common tumor suppressor genes TP53 and SMAD4 act as markers for cancer progression, occurring in high-grade dysplastic tissue and invasive EAC, respectively. Our novel in vivo tumorigenesis model demonstrates progression of Barrett's metaplasia to EAC, in which SMAD4-deficient Barrett's metaplasia cells form tumors in immunodeficient mice after a period of latency and in a dose-dependent manner. This delayed tumor growth onset suggests further drivers are required for oncogenesis, and these SMAD4-deficient cells and tumors display a greater degree of genomic instability than wildtype-SMAD4 controls. A genome-wide CRISPR-Cas9 knockout screen unveiled a synthetic lethal relationship between SMAD4-deficiency and cell cycle checkpoint inhibition, suggesting a role for SMAD4 in maintaining genomic stability and a potential novel therapeutic avenue for SMAD4-deficient EAC. Additionally, a concurrent in vivo CRISPR-Cas9 tumorigenesis screen produced tumors 4-fold faster than the previous model and identified regulators of mTOR signaling as co-operative drivers of tumorigenesis in EAC. Wildtype-SMAD4 cells failed to generate tumors despite undergoing the same genetic perturbations, indicating a potential gatekeeping effect of SMAD4 in mTOR-mediated EAC tumorigenesis. In sum, loss of SMAD4 acts as a double-edged sword, increasing genomic instability and thereby rendering EAC cells sensitive to cell cycle checkpoint inhibition, whilst simultaneously co-operating with modulated mTOR signaling to promote tumorigenesis in EAC xenograft models.
Citation Format: Julia V. Milne, Jovana R. Gotovac, Kenji M. Fujihara, Cuong P. Duong, Wayne A. Phillips, Nicholas J. Clemons. SMAD4 as a potential gatekeeper for genomic instability and mTOR-mediated tumorigenesis in esophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2671.
Abstract 268: DNA-launched HPV E7 nanoparticle vaccine induces potent anti-tumor cytolytic T-cell responses
Authors: Liaw Kevin , Xu Ziyang , Tursi Nicholas , Chokkalingam Neethu , Kulp Daniel , Weiner David 
Published: July 2021

Abstract
Nanotechnology-based approaches have provided promising tools for development of novel cancer immunotherapeutic immunogens through the decoration of multiple antigens on nanoparticle scaffolds. However, challenges with inducing robust cytolytic T cell responses critical to anti-tumor immunity, as well as purification and scalability, have hampered their clinical translation. To address these challenges, here we present the design and characterization of a DNA-launched nanoparticle vaccine displaying the HPV E7 epitope for inducing anti-tumor immune responses. We designed a nanovaccine construct by scaffolding the HPV E7 epitope with bacterial enzyme lumazine synthase. We demonstrate that through electroporation-facilitated DNA vaccination encoding the antigen-scaffold construct, this nanovaccine self-assembles in vivo into nanoparticles displaying 60 copies of the antigen on its surface. Compared to vaccination with CpG-adjuvanted HPV E7 peptide, the DNA-launched nanovaccine induced significantly greater antigen-specific CD8+ T cell responses upon stimulation with the HPV E7 peptide as well as with the epitope natively expressed on the target tumor cells. In a flank model of TC-1 lung cancer, the DNA-launched nanovaccine achieved complete tumor protection in 70% of mice when administered prophylactically. With therapeutic treatment, the nanovaccine achieved complete tumor regression in 60% of mice. In addition, anti-tumor immunity was retained upon rechallenge over 100 days after initial tumor challenge, supporting the induction of immune memory. These promising results, along with its facile characterization and scalability, support that DNA-launched nanovaccines that self-assemble in vivo can induce significant anti-tumor cellular immunity and are ideally positioned for study in clinical translation.
Citation Format: Kevin Liaw, Ziyang Xu, Nicholas Tursi, Neethu Chokkalingam, Daniel Kulp, David Weiner. DNA-launched HPV E7 nanoparticle vaccine induces potent anti-tumor cytolytic T-cell responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 268.
Abstract 2713: Preclinical models for translational immuno-oncology research: patient-derived xenografts on humanized mice
Authors: Stecklum Maria , Wulf-Goldenberg Annika , Brzezicha Bernadette , Klinghammer Konrad , Jöhrens Korinna , Walther Wolfgang , Hoffmann Jens 
Published: July 2021

Abstract
Background: The preclinical evaluation of novel immune checkpoint modulators is dependent on models with functional human immune cells. In previous experiments, we have demonstrated, that we can use either peripheral blood mononuclear cells (PBMC) or hematopoietic stem cells (HSC) to establish a humanized immune system on highly immunodeficient mice with functional T, B or NK cells. Furthermore, we determined PD-L1 expression as a predictive marker and target for immunotherapy on different patient-derived xenografts (PDX). By co-transplantation of PDX, we successfully generated a fully human tumor-immune-cell model in mice. Finally, we evaluated the functionality of the model by the treatment with checkpoint inhibitors and for combination therapies i.e. with chemotherapy or radiation.
Methods: HSC-humanized mice (HIS) were generated by i.v. transplantation of HSC. Engraftment of immune cells was monitored by FACS analysis. For PBMC-humanized mice, immune cells were implanted i.v. PD-L1 expression on PDX was determined by FACS and immunohistochemistry (IHC). PDX from 13 different entities (i.e. melanoma, lymphoma) were transplanted on HIS mice and treated with Ipilimumab (Ipi) and Nivolumab (Nivo) alone or in combination with radiation.
Results: 14 weeks after HSC transplantation up to 20% of the human immune cells in the blood were T-cells. We have transplanted more than 40 different PDX from 13 different tumor entities on HIS mice. Most of the investigated PDX (&gt;70%) successfully engrafted and showed no significant difference in tumor growth compared non-humanized mice. However, for some PDX we observed a delayed tumor growth or a complete rejection. Engraftment delay seems to correlate with the PD-L1 expression of PDX (the higher PD-L1, then the higher growth delay). Treatment with Ipi or Nivo alone or in combination led to a minor tumor growth delay and an increased percentage of T-cells in the blood and the tumor. Response showed a correlation to innate immune response and PD-L1 expression of PDX and could further be increased by combination with radiotherapy.
Conclusions: Our humanized immune-PDX models enable appropriate preclinical translational research on tumor immune biology and the evaluation of new therapies and combinations, as well as the identification and validation of biomarkers for immune therapy.
Citation Format: Maria Stecklum, Annika Wulf-Goldenberg, Bernadette Brzezicha, Konrad Klinghammer, Korinna Jöhrens, Wolfgang Walther, Jens Hoffmann. Preclinical models for translational immuno-oncology research: patient-derived xenografts on humanized mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2713.
Abstract 2728: Modulation of NFkappaB signaling influences tumor associated macrophage phenotypes in murine models of breast cancer
Authors: Bullock Kennady K. , Parker Dominique , Glass Evan B. , Hoover Alyssa , Merkel Alyssa , Maynard Richard , Wilson Andrew , Giorgio Todd , Rhoades Julie A. , Yull Fiona E. 
Published: July 2021

Abstract
Tumor associated macrophages (TAMs) often exist in high densities in breast tumors and are associated with adverse clinical outcomes. TAM repolarization as a strategy to shift the breast cancer microenvironment from immunosuppressive to immunostimulatory is an active area of research. The canonical and non-canonical NfkappaB (NFkB) signaling pathways represent potential points of intervention to influence TAM phenotypes. We have found that upregulation of the canonical NFkB signaling pathway specifically in macrophages can be used to repolarize TAMs toward an M1, anti-tumor phenotype. Using our doxycycline inducible mouse model termed IKFM, we are exploring the effects of macrophage specific upregulation of NFkB signaling on different stages of tumor growth and metastasis. In studies using the IKFM mouse model, we found that doxycycline-induced NFkB activation in macrophages in established orthotopic mammary tumors has therapeutic effects on tumor outcomes. Compared to control mice, we found that IKFM mice have reduced tumor burden in the lung, indicating prevention of metastasis. Ongoing studies are focused on understanding how macrophage specific activation of NFkB influences the metastatic niches of lung and bone; two of the most common sites of breast cancer metastasis. To move our findings towards clinical translation, we have developed an M2-macrophage targeted nanoparticle that activates NFkB signaling by delivering an siRNA against IkappaBalpha, an inhibitor of the pathway. The M2 targeted nanoparticle is currently being tested in murine models of breast cancer metastasis to both lung and bone to translate our findings from the IKFM mouse model to a pharmacological manipulation.
Citation Format: Kennady K. Bullock, Dominique Parker, Evan B. Glass, Alyssa Hoover, Alyssa Merkel, Richard Maynard, Andrew Wilson, Todd Giorgio, Julie A. Rhoades, Fiona E. Yull. Modulation of NFkappaB signaling influences tumor associated macrophage phenotypes in murine models of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2728.
Abstract 2737: Clinical and epidemiologic predictors of clonal immune responses in colorectal cancer
Authors: Gruber Stephen B. , Bonner Joseph D. , Lindsey Sidney S. , Tsai Ya-Yu , Sanz-Pamplona Rebeca , Alonso M. Henar , Melas Marilena , Rennert Hedy S. , McDonnell Kevin J. , Idos Gregory E. , Walker Christopher P. , Kast W. Martin , Da Silva Diane , Robins Harlan S. , Greenson Joel K. , Moreno Victor , Schmit Stephanie L. , Rennert Gad 
Published: July 2021

Abstract
The quantity and quality of immune responses in colorectal cancers (CRC) are widely variable and have important clinical, therapeutic, and prognostic implications. We studied clinical and epidemiologic factors that might influence T-cell quantity and clonality within colorectal adenocarcinomas to better understand the drivers of diverse immune responses. Incident cases of CRC from the Molecular Epidemiology of Colorectal Cancer Study (MECC) were interviewed, and 6,006 cases had complete epidemiologic data. Archived tumor blocks were retrieved from 3,865 (64.4%) cases, and all were reviewed by a single expert pathologist who quantified TILS/hpf. Sufficient tissue for macrodissection and measurement of TCR abundance and clonality using the immunoSEQ assay (Adaptive Biotechnologies) was available and completed for 2,750 cases. Logistic regression, negative binomial regression and linear regression models were used to evaluate potential associations between clinical and epidemiologic variables for: TILS/hpf, TCR abundance, and T-cell clonality. The stage distribution was representative of cancer incidence in the population, and the MSI-H phenotype was observed in 14.2% of cases. Clinical, pathologic, and epidemiologic variables including aspirin, alcohol, diet, hormone use, physical activity, smoking, and statins were assessed in relation to immune measures. Among other findings, &gt;5 years of statins (p&lt;0.001) and daily aspirin (p=0.037) were each strongly associated with T-cell clonality. Our study suggests that important parameters of the adaptive immune response may be mediated by modifiable factors. Mechanisms regulating immune responses in CRC may have implications for chemoprevention as well as immunotherapy.
Citation Format: Stephen B. Gruber, Joseph D. Bonner, Sidney S. Lindsey, Ya-Yu Tsai, Rebeca Sanz-Pamplona, M. Henar Alonso, Marilena Melas, Hedy S. Rennert, Kevin J. McDonnell, Gregory E. Idos, Christopher P. Walker, W. Martin Kast, Diane Da Silva, Harlan S. Robins, Joel K. Greenson, Victor Moreno, Stephanie L. Schmit, Gad Rennert. Clinical and epidemiologic predictors of clonal immune responses in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2737.
Abstract 2745: Murine high grade serous ovarian cancer (HGSOC) models replicate the human tumor microenvironment and suggest anti-tumor activities of macrophages after chemotherapy
Authors: Berlato Chiara , Heath Owen , Maniati Eleni , Gopinathan Ganga , Kotantaki Panoraia , Elorbany Samar , McDermott Jacqueline , Pegrum Colin , Szabova Ludmila , Perets Ruth , Drapkin Ronny , Bailey Peter , Annibaldi Alessandro , Barton Desmond P. , Balkwill Frances R. 
Published: July 2021

Abstract
The aim of this study is to characterize and validate similarities between the human tumor microenvironment (TME) and the TME of new HGSOC murine models and to use the models to analyze the role of tumor associated macrophages (TAMs) after chemotherapy. HGSOC has seen in the past decades only a modest reduction of mortality. This is in part due to the lack of suitable models, as the origin and mutation patterns of HGSOC were not previously understood. Despite recent advances with organoid models, murine models that represent the TME and in particular the complex interactions with the immune system are needed. We characterized the TME of six orthotopic, transplantable syngeneic murine HGSOC lines established from tumors in genetic models and compared these to patient biopsies. This analysis identified significant correlations between the transcriptome, host cell infiltrates, immune response, matrisome, vasculature and tissue modulus of mouse and human TMEs, with several stromal and malignant cell targets in common. However, each model also showed distinct differences and potential vulnerabilities that will enable us to study potential therapies. These models allowed us to extend our understanding of the role of TAMs following chemotherapy. Chemotherapy reduced the number and changed the phenotype of TAMs both in patient biopsies and in mouse models. Following chemotherapy, inflammasome activation in TAMs was also observed. Depletion of TAMs with CSFR1 inhibitors after carboplatin treatment reduced survival in a mouse model, suggesting that chemotherapy can activate sub-populations of macrophages to an anti-tumor phenotype that can sustain adaptive immunity. In conclusion, we have characterized murine transplantable models that share similarities with human HGSOC and have helped us elucidate the anti-tumor role of TAMs once activated by chemotherapy.
Citation Format: Chiara Berlato, Owen Heath, Eleni Maniati, Ganga Gopinathan, Panoraia Kotantaki, Samar Elorbany, Jacqueline McDermott, Colin Pegrum, Ludmila Szabova, Ruth Perets, Ronny Drapkin, Peter Bailey, Alessandro Annibaldi, Desmond P. Barton, Frances R. Balkwill. Murine high grade serous ovarian cancer (HGSOC) models replicate the human tumor microenvironment and suggest anti-tumor activities of macrophages after chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2745.