bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4240: In vivo assessment of AICD and cytokine release upon treatment of OKT3 and CD3 bispecific antibody in homozygous CD3EDG HuGEMM™
Authors: He Daniel XF 
Published: June 2022

Abstract
Introduction: CD3 bispecific antibodies have transformed the therapeutic landscape of immunotherapy for some hematological malignancies, however, the clinical therapeutic effects of CD3 bispecific therapies is still under investigation for solid tumors. Moreover, CD3 bispecific antibody-mediated tumor targeting as well as T cell engagement have resulted in cytokine release syndrome (CRS), increased on-target/off-tumor toxicities and poor T cell infiltration, which may affect safety and limit therapeutic efficacy. To better understand the relationship between T cell activation and systemic cytokine release in the context of CD3 bispecific antibody treatment, a homozygous human CD3EDG HuGEMM࣪ preclinical model was developed.
Methods: The homozygous CD3EDG HuGEMM mice, which express human CD3ε/CD3δ/CD3γ on the surface of T cells, were subcutaneously inoculated with MC38 or MC38-hEpCAM HuCELL™ syngeneic tumors and treated with vehicle, anti-mPD-1 (RMP1-14), OKT3, and anti-hCD3×hEpCAM. For efficacy studies, mouse body weight and tumor volume were measured twice weekly and tumor growth inhibition (TGI%) was determined. To investigate OKT3 or CD3 bispecifics-induced cytokine release, mouse body weight was monitored daily and several inflammatory and proinflammatory cytokines in the serum were detected by MSD.
Results: Firstly, anti-mPD-1 treatment (5 mg/kg and 15 mg/kg i.p.) of homozygous CD3EDG mice engrafted with MC38 syngeneic tumors led to 42% and 62% TGI, respectively. OKT3 treatment of MC38-hEpCAM bearing homozygous CD3EDG HuGEMM promoted tumor growth (TGI= -80%), likely due to activation-induced cell death (AICD) of T cells. In addition, CRS was induced within 24 hours of OKT3 dosing, with IL-2, IL-6, and TNF-α peaking 2 hr post the 1st dose, and IFN-γ, IL-10 and IL-5 peaking 6 hr post the 1st dose. In contrast, no significant cytokine release was observed upon anti-hCD3×hEpCAM treatment despite remarkable TGI, indicating that the delicate balance of in vivo T cell activation and T cell cytotoxicity is crucial for effective tumor killing by CD3 bispecific antibodies or engagers.
Conclusions: Our CD3EDG HuGEMM and HuCELL models provide a predictive platform for in vivo efficacy and safety assessment of CD3 bispecific or trispecific antibodies. The uncoupling of systemic cytokine release and T cell cytotoxicity via CD3 bispecific or trispecific antibodies provides a biological rationale to clinically explore preventative treatment approaches to avoid or reduce CRS-related toxicity, as well as combination approaches to increase selectivity and efficacy.

Citation Format: Daniel XF He. In vivo assessment of AICD and cytokine release upon treatment of OKT3 and CD3 bispecific antibody in homozygous CD3EDG HuGEMM™ [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4240.
Abstract 433: Colorectal and gastric cancer screening rates in Korea during the COVID-19 pandemic
Authors: Seo Seung Hee , Park Hyeree , Park Jong Heon , Keam Bhumsuk , Yoo Shin Hye , Shin Aesun 
Published: June 2022

Abstract
Background: The COVID-19 pandemic has disrupted healthcare delivery, which is widely discussed as the distraction effect. This study aimed to estimate the distraction effect of the COVID-19 pandemic in Korea by analyzing colorectal and gastric cancer screening rates in the years 2019 and 2020.
Methods: Information of eligible population who had colorectal and gastric cancer screening provided by the National Cancer Screening Program in the years 2019 and 2020 was collected. Participation rates were analyzed by age group, sex, geographic region, and calendar month. Percentage change was calculated by dividing the percentage point difference by the screening rate of the reference period (2019).
Results: Overall, the colorectal and gastric cancer screening rates had decreased in 2020, compared to the reference period. For colorectal cancer, the screening rate decreased from 68.3% in 2019 (5,886,319 participants/14,526,424 eligible population) to 54.6% in 2020 (5,135,218/9,410,525) For gastric cancer, the screening rates decreased from 61.9% in 2019 (7,194,489/11,625,627) to 54.6% in 2020 (6,244,491/11,439,246). In March, during the first wave, the screening rates declined sharply (percentage change: colorectal, 56.6%; gastric, 57.3%). Although the screening rates had rebounded aftermath, they declined again in December, during the third wave (percentage change: colorectal, 17.0%; gastric, 13.8%). According to specific-age group, we found a substantial decline in screening rates for older adults aged 80~84, and those over 85 (percentage change: colorectal, 19.0% & 23.0%; gastric, 17.4% & 25.1% respectively).
Conclusion: During the COVID-19 pandemic, the screening rates for both colorectal and gastric cancer decreased. There was a substantial decline during the first and the third waves of the epidemic, in March and in December. The older adults group showed the highest reduction in screening rates. However, comparing the screening rate by region and sex, we did not find a significant difference. Delayed cancer diagnosis or excess death due to distraction effect of the COVID-19 pandemic has not yet been detected in Korea, therefore, further studies are needed.
Citation Format: Seung Hee Seo, Hyeree Park, Jong Heon Park, Bhumsuk Keam, Shin Hye Yoo, Aesun Shin. Colorectal and gastric cancer screening rates in Korea during the COVID-19 pandemic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 433.
Abstract 439: Physical activity among male cancer survivors during the COVID-19 pandemic
Authors: McGrath Colleen B. , Shreves Alaina H. , Stopsack Konrad , Cheung Lilian , Fisher Ann , Markt Sarah , Mucci Lorelei A. 
Published: June 2022

Abstract
Introduction: The COVID-19 pandemic has greatly disrupted the lives of cancer survivors. Beyond being at increased risk for COVID-19 infection and severe complications, cancer survivors may be at higher risk of other consequential health outcomes compared to those without a history of cancer. Engagement in physical activity has been shown to positively affect cancer survivorship outcomes, and as such, it is important to assess physical activity habits during the pandemic of cancer survivors.
Aim: To investigate the individual-level physical activity among male cancer survivors during the COVID-19 pandemic and compare to men without cancer.
Methods: Participants of the Health Professionals Follow-up Study, enrolled since 1986, were asked to self-report health behaviors during the pandemic on three web-based questionnaires administered during the COVID-19 pandemic (baseline COVID: October 2020, first follow-up: January 2021, second follow-up: April 2021). Physical activity measures were analyzed descriptively between cancer survivors and individuals without a history of cancer. Outcomes were recoded dichotomously to reflect either: healthful (i.e., higher engagement since pandemic) vs unchanged/unhealthful behavior or high vs low engagement in an activity. Logistic regression models were employed to assess association with cancer survivor status and were adjusted for covariates such as age, race, pre-pandemic BMI, pre-pandemic physical activity, and other health information, as appropriate.
Results: Of 4,416 men who completed the baseline COVID-19 questionnaire, 962 were cancer survivors (after excluding those with non-melanoma skin cancer). Of all eligible men (median age: 78 years) reporting on physical activity, over 50% walked for at least 2-3 hours per week, over 10% used a stationary bike for at least 1 hour per week, 14% engaged in yoga for at least 1 hour per week, and nearly 20% engaged in vigorous activity for at least 1 hour per week. Further, 42% engaged in high (1+ times per day) levels of mindfulness and 24% engaged in high (1+ times per day) levels of yoga. Engagement in vigorous physical activity was significantly lower among cancer survivors compared to individuals without a history of cancer (Chi-square p = 0.01).
Conclusion: Our findings suggest older men had high engagement in physical activity during the COVID-19 pandemic, with vigorous physical activity engagement significantly lower in cancer survivors.
Citation Format: Colleen B. McGrath, Alaina H. Shreves, Konrad Stopsack, Lilian Cheung, Ann Fisher, Sarah Markt, Lorelei A. Mucci. Physical activity among male cancer survivors during the COVID-19 pandemic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 439.
Abstract 5009: DKK1 is a potential target for enhancing the efficiency of radioimmunotherapy in head and neck squamous carcinoma
Authors: YE Xinyu , Zhang JIAN , Lu Yi , Gong Yingxuan , Jiang Xinyu , Li Yueming , Wang Yinghao , Li Xiuzhi , Liu Jingwen , Quan Rencui 
Published: June 2022

Abstract
Immune checkpoint inhibitors (ICIs) have been approved to treat various types of tumors, including head and neck squamous carcinoma (HNSC). However, most HNSC patients do not respond to ICIs. Radioimmunotherapy has been proposed to enhance the immune response rate in HNSC. Herein, we aimed to explore the effect of DKK1 on radiotherapy and immunotherapy in HNSC. We collected the gene expression profile and clinical information of HNSC patients from TCGA, GEO, and ICGC. The immune cell infiltration, level of related pathways and biological processes, signature scores of gene sets of interest were assessed using CIBERSORT, GSEA or GSVA respectively. One of the genes, Dickkopf-1 (DKK1), a secreted protein which plays important roles in the Wnt signaling pathways, was identified because of its significantly higher expression in HNSC. Then, we confirmed the DKK1 expression at protein level by immunohistochemistry of HNSC tissue microarray. CCK8, apoptosis detection and survival curves were performed to investigate the response of DKK1-knockdown HSC-3 cell line to radiation. We found the mRNA and protein expression level of DKK1 was significantly higher in HNSC tissue. The DKK1high group had a shorter survival time in both disease-free survival and overall survival than the DKK1low group. The DKK1high group showed a more immunosuppressive microenvironment with lower infiltration of T cells and higher infiltration of MDSCs. Furthermore, the DKK1high group was enriched in radioresistance related to wound healing, angiogenesis, and autophagy. Patients in the DKK1high group who received radiotherapy had much poorer disease-free survival and overall survival than those in the DKK1low group. HSC-3 cell line was more sensitive to radiation after knockdown of DKK1 by siRNA. Finally, we established a risk score system based on the 9 genes from 41 DKK1-associated immunomodulators and created a nomogram model to predict the prognosis of the patients. Our data show that DKK1 can affect both radiotherapy and immunotherapy in HNSC, suggesting that DKK1 can be a potential target for radioimmunology in HNSC.
Citation Format: Xinyu YE, JIAN Zhang, Yi Lu, Yingxuan Gong, Xinyu Jiang, Yueming Li, Yinghao Wang, Xiuzhi Li, Jingwen Liu, Rencui Quan. DKK1 is a potential target for enhancing the efficiency of radioimmunotherapy in head and neck squamous carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5009.
Abstract 5014: The landscape of ERBB2 mutations in Chinese patients with solid tumors
Authors: Su Xiangyu , Zhao Hongmei 
Published: June 2022

Abstract
Background: Receptor tyrosine kinase (ERBB2) is altered by mutations and amplifications in various cancer types. Meanwhile, FDA approved some drugs to use for variants in ERBB2. However, the landscape of ERBB2 mutations and copy number variants (CNV) in pan-cancer is unknown in Chinese.
Methods: 599 gene-panel by next-generation sequencing (NGS) was performed on 2,570 patients with solid tumors including non-small cell lung cancer (NSCLC) (n = 660), esophagogastric (n = 89), colorectal (n = 966), breast (n = 156) and gastric cancer (n = 699). The mutations and CNV in ERBB2 were detected for characterize the landscape in Chinese patients with solid tumors.
Results: The frequency of single nucleotide variants (SNV) and CNV in ERBB2 was 9% and 4.3% in pan-cancer and the rate of variants was 13.3%. The most frequency of CNV was occurred in breast cancer and the last was in non-small cell lung cancer (13.5% vs 1.1%). Nevertheless, the rate of SNV in different cancer species was almost the same as in pan-cancer (mean: 8.8%). The higher rate of variants in ERBB2 was breast cancer and the lower was NSCLC. The cancer types with the highest incidence of ERBB2 variants were the following: breast (22.4%), gastric adenocarcinoma (18.3%), esophagogastric cancer (11.2%), colorectal cancer (10.8%) and NSCLC (9.7%).
Conclusion: Based on the results, the profile of variants in ERBB2 revealed more patients may profit from FDA-approval drugs in China. The patients with somatic mutations in ERBB2 are treated with trastuzumab deruxtecan and adotrastuzumab emtansine in NSCLC. The patients with amplification are treated with trastuzumab deruxtecan in most tumors, but margetuximab and chemotherapy can cure breast cancer, according to FDA-approval.
Keywords: ERBB2 mutations, CNV, SNV, solid tumors
Citation Format: Xiangyu Su, Hongmei Zhao. The landscape of ERBB2 mutations in Chinese patients with solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5014.
Abstract 5028: Integration of molecular data into cancer patient database
Authors: Chaballout Basil H. , Funkhouser Avery T. , Blair Bailey B. , Goodwin Jane L. , Strigenz Alexander M. , Arthur Connie M. , Martin Julie C. , Edenfield W. Jeffery , Blenda Anna V. 
Published: June 2022

Abstract
Background: Precision medicine holds promise of being a more effective method for treating complex diseases such as cancer. Nuanced care is needed, as the development and clinical course of cancer is multifactorial with influences from the general health status of the patient, germline and neoplastic mutations, co-morbidities, and environment including "lifestyle". To tailor an individualized treatment to the patient, such multifactorial data must be presented in an easy-to-use, easy-to-analyze fashion for providers to use effectively.
Purpose: To address the need, we have built a searchable database integrating cancer-critical gene mutation status, serum galectin protein markers, serum and tumor glycomic profiles, with clinical, demographic, and lifestyle data points of individual patients.
Methods: The initial data was acquired from breast, colon, and lung cancer patients’ serum and biopsy samples from the Prisma Health Cancer Institute Biorepository. The acquired data contains the status of 2,800 COSMIC cancer-critical gene mutations, individual patient profiles of five serum galectins, and serum and biopsy glycan structures from each patient’s glycomic profile. DNA from tumor cells was used to screen the regions frequently mutated in human cancer genes. Multiplex PCR using Ion AmpliSeq࣪ Cancer Hotspot panel v2 was performed by Precision Genetics. Enzyme-linked immunosorbent assay was employed to perform galectin profiling of cancer patient serum samples. Glycomic profiling of serum and biopsy samples was performed by the Emory Comprehensive Glycomic Core. In addition, healthy control values for galectin and glycomic profiles were obtained and added to the patient database for reference. The data is being stored using Microsoft SQL servers and is fed into an interactive web application using RStudio.
Results: Our interactive database allows care providers to amalgamate cohorts from these groups to find correlations between different data types with the possibility of finding a "stage signature" based upon a combination of genetic mutations, galectin serum levels, glycan signatures, and patient clinical data and lifestyle choices.
Conclusion: Our project provides a framework for an integrated interactive database to analyze molecular and clinical patterns across cancer stages and provides opportunities for increased diagnostic and prognostic power.
Citation Format: Basil H. Chaballout, Avery T. Funkhouser, Bailey B. Blair, Jane L. Goodwin, Alexander M. Strigenz, Connie M. Arthur, Julie C. Martin, W. Jeffery Edenfield, Anna V. Blenda. Integration of molecular data into cancer patient database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5028.
Abstract 5035: Q-omics: smart software for assisting oncology and cancer research
Authors: Yoon Sukjoon , Jeong Euna , Jeong Sumin , Lee Jieun , Kim Youngju 
Published: June 2022

Abstract
Increased multi-level omics data has enabled data-driven studies on cancer drugs, targets and biomarkers. Thus, it is necessary to develop comprehensive tools for oncologists and cancer scientists to carry out extensive data mining without computational expertise. For this purpose, we have developed innovative software that enables user-driven analyses on cancer omics data, assisted by knowledge-based smart systems.
Publicly available multi-level omics data of mutations, gene/protein expression, patient survival, immune score (tumor infiltrating cells), drug screening and RNAi (shRNA and CRISPR) screenings on patient samples and cell lines, were integrated from the TCGA, GDSC, CCLE, NCI and DepMap databases. Q-omics provides user-friendly interface for calculation and visualization of cross-associated data pairs retrieved from integrated datasets. The optimal selection of samples, datasets and/or other filtering options is guided by knowledge-bases of the software for the quick and easy finding of significant associations between data pairs. Furthermore, implemented smart algorithms prioritize significant hits based on consensus scoring methods. Consensus scoring using multiple statistical tests with varied sample (or lineage) selection, enriches noise-free, robust cross-associated pairs in the hit list.
We believe that Q-omics provide simple but powerful tools for all areas of oncology and cancer research. The latest version of Q-omics software is available at http://qomics.sookmyung.ac.kr.
Citation Format: Sukjoon Yoon, Euna Jeong, Sumin Jeong, Jieun Lee, Youngju Kim. Q-omics: smart software for assisting oncology and cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5035.
Abstract 5068: Functionalized superparamagnetic nanoparticles for theranostics of membrane-bound Hsp70 positive malignant brain tumors
Authors: Tagaeva Ruslana , Fedorov Vyacheslav , Yudintceva Natalia , Yakovleva Luidmila , Nikolaev Boris , Osnach Veronica , Shevtsov Maxim 
Published: June 2022

Abstract
Biomedical nanotechnologies based on superparamagnetic iron oxide nanoparticles (SPIONs) represent a promising instrument for malignant brain tumor theranostics. Due to their unique physico-chemical properties, they can be used for multimodal cancer therapy (including hyperthermia), diagnostics, and targeted delivery of therapeutic molecules. To enhance the tumor-homing properties of nanoparticles the latter were conjugated with bioligands (i.e., monoclonal antibodies, Fab-fragments, peptides, and proteins such serine protease granzyme B) that recognize 72 kDa membrane-bound heat shock protein (mHsp70) that is expressed on the plasma membrane of tumor cells, including multiforme glioblastoma (GBM), but not on normal corresponding cells. Therapeutic potential of magnetic conjugates can be attenuated by binding to the particles surface of granzyme B (GrB-SPIONs) that exerts pro-apoptotic activity. Functionalized particles significantly contrast-enhanced the orthotopic glioblastoma (U87 glioma in NMRI nu/nu mice, GL261 glioma in C57/Bl6 mice) in preclinical animal models when high-field (11 ) magnetic resonance tomography (Bruker) was employed. Furthermore, when GrB-SPIONs were applied, we detected a statistically significant delay of tumor progression and increase of overall animal survival. Anti-tumor activity of GrB-SPIONs was further synergistically potentiated by stereotactic radiotherapy combined with immune check-point inhibitors (i.e., CTLA-4). In conclusion, synthesized superparamagnetic nanoparticles targeting mHsp70-positive could be employed for theranostics of malignant brain tumors and translated into further clinical trials.This research was funded by the Ministry of Science and Higher Education of the Russian Federation (Agreement № 075-15-2020-901).
Citation Format: Ruslana Tagaeva, Vyacheslav Fedorov, Natalia Yudintceva, Luidmila Yakovleva, Boris Nikolaev, Veronica Osnach, Maxim Shevtsov. Functionalized superparamagnetic nanoparticles for theranostics of membrane-bound Hsp70 positive malignant brain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5068.