bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3304: Immune repertoire sequencing enables accurate clonality determination
Authors: Song Chen , Erijman Ariel , Lund Sean , Langhorst Bradley W. , Liu Pingfang 
Published: April 2023

Abstract
The study of complex immunological diseases and tumor microenvironments has advanced through recent developments in sequencing of the immune repertoire. Using this approach, the interrogation of disease progression is facilitated through analysis of millions of V(D)J combinations from B cell receptors (BCRs) and T cell receptors (TCRs). One major challenge of immune repertoire sequencing is to accurately capture the structural and sequence complexities of antibodies and TCR genes during both library preparation and bioinformatic analysis. In addition, the lack of standard reference controls makes assessing sequencing accuracy and sensitivity challenging. Here, we present a method for accurate sequencing of full-length immune gene repertoires of B cells and T cells.
RNA extracted from peripheral blood mononuclear cells (PBMCs) or tissues were used for reverse transcription, during which unique molecular identifiers (UMIs) were added to discretely barcode each mRNA molecule. BCR- and TCR-specific PCR primers were used to enrich full-length BCR and TCR sequences. We have implemented a data analysis pipeline to assemble the full length BCR/TCR transcripts and to collapse PCR copies of each mRNA fragment into a single consensus sequence using UMIs. UMI incorporation enables the absolute quantification of input RNA molecules and accurate ranking of antibody/TCR clone abundance. Furthermore, we developed an RNA control pool that contains a large dynamic range of BCR and TCR sequences with a variety of V(D)J combinations, which enables sensitivity and accuracy evaluation of BCR and TCR sequencing.
Our immune repertoire sequencing approach allows accurate clonal determination for both BCR and TCR. This technique is applicable for various applications including design of antibody chains for in vitro synthesis, investigation of T cell infiltration of tumor microenvironments, and monitoring of minimal residual disease in cancer patients.
Citation Format: Chen Song, Ariel Erijman, Sean Lund, Bradley W. Langhorst, Pingfang Liu. Immune repertoire sequencing enables accurate clonality determination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3304.
Abstract 3307: A novel targeted RNA sequencing approach for identification of aggressive prostate cancer
Authors: Fredsøe Jacob , Haldrup Christa , Nordentoft Iver , Ulhøi Benedicte , Borre Michael , Sørensen Karina D. 
Published: April 2023

Abstract
Introduction: Prostate cancer (PC) is a highly heterogeneous disease and can be either aggressive, requiring immediate treatment, or remain slow growing and even without treatment present no significant symptoms throughout the man’s life. Currently, there is an unmet need for new tools that can clearly distinguish indolent from aggressive PC in order to guide treatment decisions.PC is a highly heritable disease and so far, approximately 450 genomic regions associated with PC risk have been defined in genome-wide association studies. Most of these regions are however devoid of annotated genes and consequently the underlying mechanisms behind the associations are not easily elucidated. Accordingly, yet uncharacterized genes in PC-associated regions could be involved in PC development/progression.
Methods: We quantified gene expression levels by Kallisto on total RNAseq data from fresh frozen prostate tissue samples from 134 localized PCs, 33 matched adjacent normal (AN) areas as well as 15 PC cell lines. Furthermore, we performed targeted RNAseq covering approximately seven million base pairs divided among 101 PC-risk associated regions (GWAS hits) for in-depth transcriptomic analyses in the same set of samples. HISAT and StringTie were used to identify novel transcripts (genes) with the criteria that a given gene had to have at least 10 reads in more than 50% of all samples to be included. Patient genotyping was performed on Illumina’s global screening array.
Results: In totalRNA seq data we observed significant dysregulation of 10,256 genes (5,685 up- and 4,571 downregulated) between AN and localized PC, including upregulation of know PC-associated genes such as SIM2, PCAT7, TDRD1, and TFF3. Interestingly, we found a correlation between high transcription of TFF3 and high risk of biochemical recurrence (BCR) after radical prostatectomy and furthermore a trans-acting eQTL, the PC-risk associated SNP rs1938781. Here, heterozygote patients with the risk-allele had higher risk of BCR than patients homozygous for the reference allele, indicating a potential functional relationship between the PC risk-SNP and TFF3. Additionally, we detected 207 previously unannotated non-coding genes in the capture RNAseq data, where 148 (71.5%) were undetectable in the matched total RNAseq data indicating the existence of stably albeit lowly expressed genes in the genomic areas containing PC-risk SNPs.
Citation Format: Jacob Fredsøe, Christa Haldrup, Iver Nordentoft, Benedicte Ulhøi, Michael Borre, Karina D. Sørensen. A novel targeted RNA sequencing approach for identification of aggressive prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3307.
Abstract 3308: Predictive biomarkers of response to immune checkpoint inhibitors in metastatic renal cell carcinoma
Authors: Motoshima Takanobu , Miura Yuji , Amami Toshiki , Kitano Shigeyasu , Baba Masaya , Kamba Tomomi 
Published: April 2023

Abstract
Background: Since the introduction of Immune checkpoint inhibitors (ICIs) combination therapy to renal cancer treatment, it has revolutionized the treatment of renal cancer, with many reports of excellent therapeutic effects. However, it is not known which patients will benefit the most.
Materials and methods: PBMC(Peripheral Blood Mononuclear Cells)samples were collected prospectively from patients with advanced and metastatic renal cell carcinoma (RCC) prior to initiation of ICI treatment (baseline) and 2 or 3 weeks after the first cycle of ICI treatment (post-dose 1). We collected PBMCs from 24 patients with a cell count of more than 50,000 were analyzed using antibodies that distinguishCD4 and CD8 cells including Effector, Memory cells population, B cells, Monocyte, NK(Natural Killer) cells, MDSC(Myeloid-Derived Suppressor Cells ), DC(Dendritic cells), CD4 (Th1, Th2, Th17, Tfh), Immune checkpoint molecules including CD223 (LAG3), CD279 (PD1), TIM3, CD152 (CTLA4), CD278 (ICOS), FOXP3.
Results: First, we compared the Fold Change (FC) before and after drug administration in the group that did not respond to treatment (SD: Stable Disease or PD: Progressive disease) and the group that did respond to treatment (PR: Partial Response, CR: Complete Response). The results showed that CD4 positive cells (non-responder Median 0.79 vs responder Median 1.64, p=0.0317, respectively), monocytes: CD56-HLADR+ (non-responder Median 0.87 vs responder Median 1.20, p=0.0159, respectively), but not in other cell populations.Next, we compared the groups that did and did not respond to treatment before and after treatment. We could not identify any biomarker cell population before treatment, the number of CD4 Effector cells (CD4+CD45RO-CD197-) was significantly higher in the post-treatment (PD1) group (PR or CR) than in the non-treatment group (SD or PD). (p=0.0303, respectively)
Conclusion: Elevation of CD4 positive cells and monocytes (CD56-HLADR+) before and after treatment and the number of CD4 Effector cells (CD4+CD45RO-CD197-) after treatment may be biomarkers of treatment response.
Citation Format: Takanobu Motoshima, Yuji Miura, Toshiki Amami, Shigeyasu Kitano, Masaya Baba, Tomomi Kamba. Predictive biomarkers of response to immune checkpoint inhibitors in metastatic renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3308.
Abstract 3352: Development and validation of a serum microRNA-based diagnostic model for early detection of multiple cancers
Authors: Zhou Grace , Hu Hai 
Published: April 2023

Abstract
Introduction: Detecting cancer early improves patients’ survival rate. We previously developed a serum 4-microRNA (miRNA) diagnostic model using lung cancer patient samples, which detected 12 cancer types with high accuracy (Zhang and Hu 2022 Cancers). In this study, we aimed to develop a new diagnostic model based on samples from ovarian cancer patients to evaluate whether model performance depends on the initial cancer type used.
Patients and Methods: Our previous work assembled a serum miRNA microarray dataset from 4 individual datasets from GEO, including 3604 patients across 13 cancer types and 3932 non-cancer controls. In this study, we composed a training set of 191 ovarian cancer patients and 191 non-cancer controls matched by age and gender. Limma analysis was performed to rank differentially expressed miRNAs, and 10-fold cross-validation was used to determine the optimal number of top miRNAs for the final diagnostic model. Model performance was evaluated by area under the curve (AUC) of Receiver Operating Characteristic (ROC) curve analysis, and sensitivity and specificity, using samples not utilized in current or previous model development.
Results: Using this training set, a 10-miRNA model was developed which showed an improved AUC 0.994 as compared to 0.973 from our previous model for ovarian cancer in the testing set. AUC was also substantially improved on sarcoma and breast cancers. With 99.1% specificity, the current model demonstrated at least 70% sensitivity for 10 of the 13 cancer types, comparable to the previous model with 99.3% specificity (Table 1).
Conclusion: Our study showed that blood miRNA-based diagnostic models can be developed for detecting multiple cancers with high accuracy, regardless of initial cancer types used in model development. These results suggested that tumors of different cancers shed common types of miRNAs into the bloodstream, supporting the use of circulating miRNAs as a biomarker for multi-cancer early detection.
ABLE 1. Diagnostic Model Performance Cancer Type N Current Model AUC Current Model Sensitivity Previous Model AUC Previous Model Sensitivity Ovarian 142 0.994 0.80 0.973 0.69 Lung 1358 0.998 0.93 0.999 0.99 Pancreatic 149 0.992 0.76 0.983 0.83 Prostate 40 0.998 0.95 0.996 0.92 Sarcoma 132 0.973 0.52 0.876 0.72 Esophageal 124 0.995 0.90 0.990 0.85 Gastric 150 0.998 0.93 0.999 1.00 Glioma 40 0.985 0.68 0.996 0.88 Liver 348 0.988 0.70 0.979 0.84 Biliary Tract 40 0.996 0.85 0.998 0.98 Bladder 392 0.996 0.95 0.998 0.98 Breast 135 0.946 0.10 0.378 0.00 Colorectal 155 0.99 0.83 0.955 0.86
Citation Format: Grace Zhou, Hai Hu. Development and validation of a serum microRNA-based diagnostic model for early detection of multiple cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3352.
Abstract 338: Regulation of gap junction intercellular communication in pancreatic cancer cells
Authors: Nguyen Annelise , Doan My 
Published: April 2023

Abstract
According to the American Cancer Society, approximately 62,210 people (32,970 men and 29,240 women) in the United States are estimated to be diagnosed with pancreatic cancer by the end of 2022. An estimated 80% of these patients will die as a result of pancreatic cancer. This type of cancer has been challenging to treat due to the complexity of tumor cells, tumor aggressiveness, current drug availability, and drug delivery. A new class of substituted quinolines, known as PQ compounds, acts as gap junction enhancer, having the ability to increase the gap junctional intercellular communication cancerous cells. The goal of this project is to provide a new approach to treat pancreatic cancer via restoration of gap junctional intercellular communication and combining treatment with antineoplastic drugs. One approach was to increase cell communication of pancreatic cancer cells using small molecules, PQs, and hence allowing antineoplastic drugs to effectively travel from cell to cell. Pancreatic cancer cells were treated with gap junction enhancers, PQs, in the presence and absence of antineoplastic drugs. Interestingly, 5-FU significantly decreased the expression of gap junction protein, connexin 43, compared to control and PQ1 treatments. PQ1 has demonstrated to increase Cx43 expression and increase 4.5-fold of gap junction activity. Furthermore, cells treated with nilotinib have a significant effect on PANC-1 cells. Current studies focus on functional assays to determine if PQ1 can increase cell-cell communication, allowing a reduced concentration of antineoplastic drugs to be used. Overall, the findings provide an initial insight to a new approach in treating pancreatic cancer.
Citation Format: Annelise Nguyen, My Doan. Regulation of gap junction intercellular communication in pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 338.
Abstract 3382: Detection of CTCs using a micro-channel combined fluid dynamics and electrophoresis in colorectal cancer
Authors: Ohta Ryo , Yamada Takeshi , Taniai Nobuhiko , Yoshida Hiroshi 
Published: April 2023

Abstract
Background: Circulating tumor cells (CTCs) are tumor cells that can be isolated from peripheral blood. Investigation of CTCs might allow comprehensive studies at the DNA, RNA, and protein. However, fewer CTCs generally can be collected from patients with colorectal cancer, limiting the possibility of clinical applications of CTC analysis despite the development of many different methods. We have developed a micro-channel device that integrates hydrodynamic filtration (HDF) capable of size separation and dielectrophoresis (DEP) capable of electrical property separation, using peripheral blood from colorectal cancer patients.
Method: A separation test was performed using a whole peripheral blood sample obtained from colorectal cancer patients with KRASmutation in the tumor tissue. The sample blood was diluted 2-fold with PBS, and red blood cells and plasma were removed using HDF. After that, Leukocytes and CTCs were separated in the same channel by DEP. DNA was extracted from CTCs (port 1) and leucocyte fraction (port 2), and KRAS mutations were detected using droplet digital PCR. In order to evaluate the separated fractions, microwell slide was used for evaluation by nuclear staining, CD45 and EpCAM antibody staining.
Results: 52 colorectal cancer patients were participated. The median age of patients was 71 years, 38 (73%) were male. Twenty-eight (53.9%) had colon cancers. Four stage III and 48 stage IV patients were included. The quality of DNA extracted from all patients were suitable for molecular genetic analysis. The DNA concentration of port 1 was significantly lower than that of port 2 (371 ng/mL vs 36667 ng/mL, P&lt;0.001). Using droplet digital PCR, KRAS mutations were detected in the port 1 of 8 (15.4%) patients and in port 2 of 15 (28.8%) patients. In 35.5% of patients, KRAS mutations were detected in either port 1 or port 2.
Conclusion: This device does not require pretreatment and is easy to extract CTCs. Since CTCs are contaminated with the leukocyte fraction, it is necessary to improve the accuracy of CTCs collection by adjusting the conditions of DEP.
Citation Format: Ryo Ohta, Takeshi Yamada, Nobuhiko Taniai, Hiroshi Yoshida. Detection of CTCs using a micro-channel combined fluid dynamics and electrophoresis in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3382.
Abstract 341: Critical role of defensins in respiratory viral infection induced breast cancer progression
Authors: Ali Umer , Tiriveedhi Venkataswarup 
Published: April 2023

Abstract
Respiratory viral infections (RVI) such as influenza and COVID19 impact the host systemic immune system along with causing deleterious chronic inflammatory responses and respiratory distress. While the role of chronic inflammation in cancer is well-established, the role of RVI on tumorigenesis is poorly defined. To study the role of RVI on breast cancer, we first infected murine respiratory epithelial cells (mRES) with murine sendai virus (mSV), an analog for human parainfluenza virus. These infected mRES were co-cultured with 4T1 murine breast cancer cells in 1:1 dilution on a single 2D plate and also in trans-well format. Both in co-culture and transwell culture we saw a 40-80% (p&lt;0.05) increased proliferation of breast cancer cells. Similarly, when 4T1 cells were treated with the supernatant collected from infected mRES cells in 1:5 dilution, also demonstrated a 2.3 fold increased breast cancer cell proliferation. The cytokine analysis from the supernatant collected from infected mRES cells demonstrated a 17-23 fold enhanced secretion of α/β-defensins. Direct treatment of α-defensin (cyptidin-4, 10 pg/mL) and β-defensin-3 (mBD3, 20 pg/mL) on 4T1 cells demonstrated enhanced expression of chemokine metastatic receptor, CXCR4 (4.3 fold), angiogenic factor, VEGF (12.8 fold) and cell division favoring factor, CDK2 (8.1 fold). Further, analysis of infected mRES cells demonstrated upregulation of toll-like receptor 2 (TLR2) and NOD-like receptor protein 3 (NLRP3) expression. Interesting, co-cultured of infected mRES with syngeneic murine CD4 T cells induced exhaustion phenotype (PD1+ and CTLA4+) differentiation of CD4 T cells. Taken together, these data suggest that respiratory viral infections through induction of cancer cell proliferation and inhibiting anti-tumor adaptive immune responses promote breast cancer proliferation.
Citation Format: Umer Ali, Venkataswarup Tiriveedhi. Critical role of defensins in respiratory viral infection induced breast cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 341.
Abstract 3410: AVATASCAN®, a pioneer of functional precision medicine in guiding clinical decision-making
Authors: Her Nam-Gu , Lee Gi Ju , Hyun Seung Yoon , Park San Ha , Ahn Jae Woo , Kang Ji Soo , Toh Hong Boon , Nam Do-Hyun 
Published: April 2023

Abstract
Precision medicine refers to the tailoring of individual therapeutics based on each patient’s genetic, phenotypic, and clinical characteristics, therefore seeking the most effective treatment for the patient. With recent advances in genome sequencing technology, it was anticipated that identifying specific genetic alterations would contribute greatly to the realization of precision medicine. However, most cancer patients do not benefit from genomic precision medicine, as shown in recent Next Generation Sequencing (NGS)-driven clinical trials. Functional precision medicine directly uses patient tumor cells to test their ex vivo responses to diverse drugs to predict the most effective drugs. Functional precision medicine is emerging because it provides immediate translatable information to select drugs among clinically available therapeutics. AVATASCAN®, developed by Samsung Medical Center and AimedBio Inc., is a robust and accurate high throughput functional precision medicine platform with more than 1,500 historical sample data. AVATASCAN® has tested more than 1,500 cancer patient samples across 14 different tumor types, including glioblastoma, lung, colorectal, stomach and breast cancers. We achieved a tissue culture success rate and a drug screening success rate of more than 90% in most tumor types. A retrospective analysis of the clinical outcomes of patients given matched drugs demonstrated actual complete/partial response in 85% of AVATASCAN® screening responders. Recognizing its potential for clinical application, AVATASCAN® was selected as one of the datasets referenced by the pediatric tumor board at Seoul National University Hospital for clinical decision-making. Furthermore, AVATASCAN® is now available in Singapore and Thailand as an early-access, premium precision medicine service. Overall, we present compelling evidence that AVATASCAN® is a valuable platform for personalized cancer therapy. Therefore, we are moving forward to adopt and expand this platform in clinical applications.
Citation Format: Nam-Gu Her, Gi Ju Lee, Seung Yoon Hyun, San Ha Park, Jae Woo Ahn, Ji Soo Kang, Hong Boon Toh, Do-Hyun Nam. AVATASCAN®, a pioneer of functional precision medicine in guiding clinical decision-making [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3410.