bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2394: Discovery of small anti-PD-L1 peptides for cancer immunotherapy
Authors: Liu Hao , Zhao Zhen , Li Yuanke , Cheng Kun 
Published: August 2019

Abstract
Immunotherapy using checkpoint inhibitors, especially PD-1/PD-L1 inhibitors, has now evolved into the most promising therapy for cancer patients. However, most of these inhibitors are monoclonal antibodies, and their large size may limit their tumor penetration, leading to suboptimal efficacy. As a result, there has been a growing interest in developing low-molecular-weight checkpoint inhibitors. Using a phage display peptide library, we discover small peptide-based anti-PD-L1 inhibitors to block the PD-1/PD-L1 interaction. These peptides exhibit high affinity and specificity to human PD-L1 as well as PD-L1-positive human cancer cells. Molecular docking studies indicate that the CLP002 peptide specifically binds to PD-L1 at the residues where PD-L1 interacts with PD-1. Compared to anti-PD-L1 antibody, the anti-PD-L1 peptides exhibited better tumor penetration in a 3D tumor spheroid model. The CLP002 peptide restores proliferation and prevents apoptosis of T cells that are co-cultured with cancer cells. The CLP002 peptide also inhibits tumor growth and increases survival of CT26 tumor-bearing mice, suggesting that the CLP002 peptide represents a promising low-molecular-weight checkpoint inhibitor for cancer immunotherapy.
Citation Format: Hao Liu, Zhen Zhao, Yuanke Li, Kun Cheng. Discovery of small anti-PD-L1 peptides for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2394.
Abstract 2416: Vitamin D concentration and the risks of Barrett’s esophagus and esophageal adenocarcinoma: A Mendelian randomization study
Authors: Dong Jing , Thrift Aaron 
Published: August 2019

Abstract
Background Epidemiological studies on circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risks of esophageal adenocarcinoma (EAC) have shown conflicting results. Here we conducted a Mendelian randomization (MR) study to determine the associations between circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risks of EAC and its precursor, Barrett’s esophagus (BE).
Methods We conducted a MR study using a two-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs) (rs3755967, rs10741657, rs12785878, rs10745742, rs8018720 and rs17216707) associated with circulating 25(OH)D concentrations were used as instrumental variables. Data from 6,167 BE patients, 4,112 EAC patients and 17,159 control participants were from studies participating in the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON), as well as studies from Bonn, Germany, and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC.
Results Overall, we found no evidence for an association between genetically estimated 25(OH)D concentrations and the risk of BE or EAC. The odds ratio (OR) per standard deviation unit increase in genetically estimated 25(OH)D concentrations for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% confidence interval, CI, 0.77-1.92; P = 0.41). The OR for EAC risk estimated by combining the individual SNP association using inverse variance weighting was 0.68 (95% CI, 0.39-1.19; P = 0.18).
Conclusions This Mendelian randomization study found that genetically estimated low 25(OH)D concentrations were not associated with increased risks of BE or EAC.
Citation Format: Jing Dong, Aaron Thrift. Vitamin D concentration and the risks of Barrett’s esophagus and esophageal adenocarcinoma: A Mendelian randomization study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2416.
Abstract 2430: Assessing patient navigation and support services at FQHCs
Authors: Aponte-Soto Lisa 
Published: August 2019

Abstract
Cancer is the leading cause of morbidity and mortality for Latinx followed by African Americans (CDC, 2017). Screening can increase the rate of early detection and treatment success. However, the rates of compliance for screening are typically lower among Latinx, which may contribute to decreased diagnosis and increased risk of disease in comparison to their Euro-American counterparts (ACS, 2015). Access to screening services and ability to pay are among the commonly cited barriers for screening compliance. The IDPH recommends incorporating patient navigator (PN) models in community health clinics and communitywide events to increase health literacy, knowledge, and delivery, and quality of care including compliance with screening methods. The University of Illinois (UI) Cancer Center (UICC) works in partnership with the UI Health Mile Square Health Center (MSHC) to implement a bilingual, bicultural PN model for conducting comprehensive cancer prevention and screening services among Latinx, African Americans, and underserved communities in Chicago. A mixed methods approach was used to evaluate the patients’ perceptions and experiences with patient navigator encounters and support services. The authors conducted a semi-structured interviews and abstracted data from patient records. Provider interviews were conducted to understand provider knowledge and attitudes of navigator services. Navigator interviews captured benefits and challenges of incorporating navigation services at the clinics. Data were entered in REDCap and analyzed using Dedoose v. 8.0.42. This paper validates the implementation of PN models at federally qualified health centers (FQHCs) as an asset to patients and providers in facilitating health education, increasing patient screening compliance, and improving access to health care services. Comprehensive cancer screening maximizes resources and improves the quality of life and health outcomes of underserved Latinx and African American patients who are navigated to services. PN-provider partnerships are introduced as a hallmark of the program’s success in identifying at-risk patients and navigating them to appropriate and timely medical screening, diagnostic, and treatment services. Future directions for incorporating and evaluating culturally responsive, bilingual, bicultural PN models at FQHCs, community clinics, and school based clinics are shared to inform public policy for rapid cycle monitoring of protective health cancer interventions and early detection services for Latinx and African American patients in Chicago.
Citation Format: Lisa Aponte-Soto. Assessing patient navigation and support services at FQHCs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2430.
Abstract 2432: Prevalence of depression and other chronic diseases among uninsured cancer survivors: A free clinic study
Authors: Mirza Sayeef , Rahman Shams , Macdonald Madeline , Towne Alexandra , Robinson Katherine , Todd Amber , Wang Wei , Wathington Deanna 
Published: August 2019

Abstract
Introduction: Free clinics play an important role in providing health care services to the poor and uninsured. Limited data exist on chronic disease burden and patient characteristics of cancer survivors outside the network of insured health systems. In this study we describe characteristics of cancer patients utilizing free clinics for chronic disease management and mental health services in order to evaluate associations between chronic conditions.
Methods: Nine free clinics in the Tampa Bay area were included in this study. A retrospective review of patient charts from 01/01/2016 to 12/31/2017 was conducted. Data on patient characteristics and prevalence of chronic diseases were abstracted through an online questionnaire using Redcap software. Patients with a documented history of cancer were considered cancer survivors. Chi-square test was used to compare patient characteristics and p-values were reported. Logistic regressions were used to examine associations between diseases and socio-demographic factors. Odds ratios (OR) and 95% confidence intervals (CI) were reported.
Results: From 2016 to 2017, 208 cancer survivors were managed in nine free clinics. The average age was 54 years and 138 (66%) were women. The prevalence of depression was 11.14%. The prevalence of depression was higher among women (12.7%) compared to men (8.8%), p-value 0.001. The prevalence was significantly highest among patients who were 18-44 years, non-Hispanics, white race, unemployed and considered low-income. In univariate analyses, the prevalence of depression was significantly associated with cancer (OR 2.12; 95%CI: 1.23-3.67), diabetes (OR 1.59; 95%CI: 1.21-2.08), cerebrovascular accident (OR 3.25; 95%CI: 1.71-6.21), cardiovascular disease (OR 2.10; 95%CI: 1.26-3.51), hypertension (OR 1.96; 95%CI: 1.58-2.43), and hyperlipidemia (OR 2.30; 95%CI: 1.79-2.94). Unemployment, lower income level, and higher BMI were also factors positively associated with the prevalence of depression. Additional relationships and multivariate analyses are available.
Conclusion: Despite having access to limited resources, free clinics receive mainly poor, women, middle-aged, and uninsured patients. Comorbidities such as cancer and other chronic conditions are often directly associated with depression among patients managed in free clinics. Mental health support is critically needed in free clinics, especially for those who are cancer survivors.
Citation Format: Sayeef Mirza, Shams Rahman, Madeline Macdonald, Alexandra Towne, Katherine Robinson, Amber Todd, Wei Wang, Deanna Wathington. Prevalence of depression and other chronic diseases among uninsured cancer survivors: A free clinic study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2432.
Abstract 2437: Microfluidic device integrated with lipid nanoprobe for extracellular vesicle isolation toward non-invasive cancer diagnosis
Authors: Zheng Siyang , Wan Yuan , Maurer Mackenzie , Xia Yi-Qiu , Hao Si-Jie , Zhang Wen-Long , Yee Nelson S. 
Published: August 2019

Abstract
Extracellular vesicles (EVs) can mediate intercellular communication by transferring cargo proteins and nucleic acids between cells. Recently, they have been demonstrated for potential value in cancer diagnostics and treatment monitoring. However, relevant clinical translation is mainly limited by technical challenges in EV isolation. We previously reported lipid nanoprobes, which is a nanomaterial system of labeling probe and capture probe. The labeling probe is constructed with a lipid molecule as the active component to label EVs rapidly and spontaneously with high efficiency, while the capture probe can isolate labeled EVs magnetically. Herein, we report on the development of a microfluidic device with integrated lipid nanoprobe for on-chip EV isolation towards instrument development for clinical translation. The nanostructured substrate of the device is integrated with a micromixer for one-step isolation of EVs from 1-ml plasma. We validated the device with plasma collected from pancreatic cancer patients, followed by DNA mutation detection of EV cargo. Size-tunable nanostructures are fabricated by patterning high-resolution iron thin films on fused silica substrates. By judicious thermal annealing, homogeneously dispersed iron nanoparticles are formed by fission and fusion on the substrate, which are served as a mask for silica dry-etching. Subsequently, selected lipid nanoprobes, which can instantaneously insert into lipid bilayers of EVs, are grafted onto the nanostructured substrate in a micromixer. This platform is verified first to isolate cultured cancer cell-derived EVs spiked-in plasma samples that emulated clinical samples. This platform is further applied to isolate EVs from pancreatic cancer patients’ plasma and identified KRASmutations in EV DNA with highly sensitive droplet digital PCR. Together, this platform enables rapid and efficient isolation of EVs from plasma specimens, and thus, holds great potential in clinical translation.
Citation Format: Siyang Zheng, Yuan Wan, Mackenzie Maurer, Yi-Qiu Xia, Si-Jie Hao, Wen-Long Zhang, Nelson S. Yee. Microfluidic device integrated with lipid nanoprobe for extracellular vesicle isolation toward non-invasive cancer diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2437.
Abstract 2439: A semi-supervised deconvolution method for quantifying the composition and activity of tumor-infiltrating cell types
Authors: Chang Wennan , Wan Changlin , Sun Yifan , Han Yan , Qi Siyuan , Lu Xiongbin , Cao Sha , Zhang Chi 
Published: August 2019

Abstract
Tumor microenvironment (TME) plays a key role in tumorigenesis, disease progression and the acquirement of drug resistance. An accurate assessment of TME cellular compositions may not only shed light on how TME interacts with cancer cells, but also bring new insights for translational researchers in studying the non-responding mechanism of immunotherapy. Traditional deconvolution methods infer the relative proportions of predefined cell types based on a tissue omics data through either regression- or enrichment- based approaches. However, there are several challenges that remain unsolved in the current formulations, including (1) identifying the Immune/Stromal (I/S) cell types that truly exists in a TME, (2) identifying the marker genes for each cell type that are specifically expressed by one or a few I/S cell types in a TME, (3) co-linearity among to-be-assessed I/S proportions due to their co-infiltration. We have developed a novel semi-supervised deconvolution method namely ICTD (Inference of Cell types and Deconvolution), addressing the three challenges via (i) developing a Bi-Cross Validation (BCV) based matrix rank test to assess the significance level of the existence of cell types and signature genes, (ii) utilizing a constrained Non-negative Matrix Factorization (NMF) to eliminate the effect of co-linearity. We validated ICTD on bulk tumor datasets simulated using single-cell RNA-seq data. Our analysis suggested that ICTD has a largely improved prediction accuracy of TME compositions comparing to existing methods, and particularly, it is capable of identifying novel or sub-cell types. We applied our method to TCGA and other gene expression data of breast and prostate cancer. Subsets of CD8+ T cells with varied cytotoxicity levels and subtypes of fibroblast cells were identified. Moreover, integrated with an analysis of an independent single-cell and cell line gene expression dataset, we identified genes specifically expressed by cancer cells that are associated with decreased T cell cytotoxicity level.
Citation Format: Wennan Chang, Changlin Wan, Yifan Sun, Yan Han, Siyuan Qi, Xiongbin Lu, Sha Cao, Chi Zhang. A semi-supervised deconvolution method for quantifying the composition and activity of tumor-infiltrating cell types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2439.
Abstract 244: Inhibition of atypical PKC signaling enhances the sensitivity of glioblastoma cells towards Temozolomide therapy
Authors: Dey Avijit , Patel Rekha , Smalley Tracess , Ratnayake Wishrawana Sarathi , Islam Anisul , Acevedo-Duncan Mildred 
Published: August 2019

Abstract
Glioblastoma is a highly aggressive brain cancer which has a mean survival rate of only 12 months. Current treatment options of glioblastoma include chemotherapy and limited surgical resection. Temozolomide (TMZ) is the current therapeutic choice for chemotherapy but has severe limitations due to development of resistance that occurs by genetic modification and constitutive activation of several other pathways. Therefore, to overcome Temozolomide resistance and to prevent recurrence of the disease a more effective therapeutic approach is required. One of the signaling pathways that contribute to the aggressive behavior of glioma cells is the activation of PKC signaling. Of the various PKC isoforms, the atypical PKCs, PKC ζ and ι were found to be over-expressed in glioblastoma tissue samples compared with normal brain tissue and high atypical PKC levels were correlated with increased cellular proliferation and invasiveness of glioma cells. [4-(5-amino-4-carbamoylimidazol-1-yl)-2, 3-dihydroxycyclopentyl] methyl dihydrogen phosphate also known as ICA-1 was used as a specific inhibitor of PKC-ι and [8-hydroxynaphthalene-1,3,6-trisulfonic acid] also known as ζ-Stat was used as a specific inhibitor of PKC- ζ. T98G and U87 glioblastoma cells were treated with ICA-1 monotherapy (7.5µM), ζ-stat monotherapy (10 µM), TMZ monotherapy at varying doses, TMZ combined with ICA-1 (7.5µM) and TMZ combined with ζ-stat (10 µM) for five consecutive days and analyzed for cell viability by WST assay. Results exhibited that ICA (7.5µM) when combined with TMZ showed significantly increased cytotoxicity compared to TMZ monotherapy. Annexin-V/PI assay revealed that combination treatment with TMZ and ICA nucleotide (7.5µM) significantly increased the number of dead cells and the number of cells undergoing late apoptosis when compared to TMZ monotherapy. This study offers the first evidence for the novel combination of ICA-1 with TMZ to induce robust apoptosis in a Caspase-3 mediated mechanism. Scratch assay results also showed that inhibition of PKC-ζ by ζ-Stat lead to decreased invasion compared to control. Our studies suggest that atypical PKCs particularly PKC-ι might be an important therapeutic target in the treatment of glioblastoma.
Citation Format: Avijit Dey, Rekha Patel, Tracess Smalley, Wishrawana Sarathi Ratnayake, Anisul Islam, Mildred Acevedo-Duncan. Inhibition of atypical PKC signaling enhances the sensitivity of glioblastoma cells towards Temozolomide therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 244.
Abstract 2442: Assessing how macrophages attain distinct iron handling phenotypes in a tumor via a mathematical model
Authors: Vieira Luis Sordo , Masison Joseph , Adams Jacqueline , Torti Suzy , Laubenbacher Reinhard , Chifman Julia 
Published: August 2019

Abstract
Tumor-associated macrophages are critical regulators of iron levels. It is well established that macrophages display distinct iron handling phenotypes based on the several signals they receive from other cells in the tumor microenvironment. In order to shed light on how macrophages respond to these different signals, we are building a knowledge-based mathematical model for how macrophages attain distinct, yet related, iron handling capabilities.
Citation Format: Luis Sordo Vieira, Joseph Masison, Jacqueline Adams, Suzy Torti, Reinhard Laubenbacher, Julia Chifman. Assessing how macrophages attain distinct iron handling phenotypes in a tumor via a mathematical model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2442.
Abstract 2456: NetZen: A comprehensive network-based pathway and target discovery platform
Authors: Le Son , Riva Alberto , Deng Changwang , Tran David D. 
Published: August 2019

Abstract
BACKGROUND: Success in precision medicine depends on the ability to accurately and rapidly identify master regulators of critical gene subnetworks. To achieve this goal requires a seamless computational target discovery platform that integrates global network visualization with identification of master regulatory subnetworks (MRS) and their key influencers.
METHODS: We have created NetZen - a computer cluster-capable computational suite allowing for 1) robust network generation with million edges; 2) network-based MRS identification; 3) hierarchical analysis with automated annotations; and 4) whole-network 3D visualization of all 20,000 genes. To identify cancer MRS, we applied NetZen to expression datasets of tumors and normal tissues, tumor-initiating cells (TICs), non-TIC cancer cells, and normal stem and non-stem cells from TCGA, GEO and internal sources. For validation, we introduced these subnetworks in normal cells to recapitulate TIC phenotypes in vivo or disrupted them in patients-derived TICs and mouse xenografts (PDX). To identify MRS of mortality, we applied NetZen to survival data in TCGA.
RESULTS: Networks of 28 human cancers were generated, integrating transcriptomics, microRNAs, proteomics, and clinical data. For cancers with TIC datasets, we identified TIC-specific MRS with clear-cut hierarchy controlling immune surveillance, EMT and developmental functions. Interestingly, in some cancers, the immune subnetwork including immune checkpoints was entirely encompassed in the developmental subnetwork. We present representative validation on glioblastoma TIC (GIC) MRS with features common in other cancers’ TICs. Exogenous introduction of this subnetwork in normal astrocytes forced them to become GICs and form tumors in mice. Disrupting this subnetwork in 10 independent PDXs profoundly blunted tumor growth and prolonged survival. Lastly, we present detailed MRS of mortality analysis of multiple cancer types and identify common pathways directly influencing outcomes.
DISCUSSION: NetZen provides a complete solution to big data analysis by effortlessly processing million-edge hierarchical networks with biological insights through automated annotations. The findings that the immune and developmental subnetworks were intimately linked suggest that immune escape by TICs is intrinsic of cellular transformation rather than a product of selection. Lastly, detailed network hierarchy provides a logical roadmap for cancer therapeutic development.
Citation Format: Son Le, Alberto Riva, Changwang Deng, David D. Tran. NetZen: A comprehensive network-based pathway and target discovery platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2456.