tbuckley/cabot-search huggingface dataset:
Abstract 1155: Subcutaneous intratumoral administration of a novel oncolytic virus leads to eradication of peritoneal disseminated pancreatic cancer in nude mice
Authors: Zhifang Zhang, Annie Yang, Shyambabu Chaurasiya, Sang-In Kim, Anthony K. Park, Jianming Lu, Susanne G. Warner, Yuman Fong, Yanghee Woo
Journal: Cancer Research (2021)

Abstract Introduction: We investigated a novel oncolytic virus, CF33-hNIS-antiPDL1, which has shown robust preclinical activity against numerous solid tumors, for its ability to track and kill distant peritoneal metastases after local virus administration in vivo. Methods: In this study, we used CF33-hNIS-antiPDL1, a replication competent orthopoxviral chimera engineered to express the human sodium iodine symporter (hNIS) and anti-human programmed death ligand 1 (PD-L1) antibody. To create our mouse model, we inoculated the human pancreatic cell line - AsPC1-ffluc (5x106 cells/site) in both the subcutaneous space and the peritoneum in nude mice. After confirming presence of tumor, the mice were divided into two groups; and treated with either 1) three doses of intratumoral (IT) CF33-hNIS-antiPDL1 (3x105 plaque forming units; (n=8) or 2) PBS (n=4). Each mouse was assessed for the following: tumor burden (bioluminescence imaging); CF33-hNIS-antiPDL1 tracking and replication in tumors (124I based PET imaging); and survival (time to death). Results: By week 2, the animals in the CF33-hNIS-antiPDL1 treated group compared to the PBS treated group had significantly decreased tumor burden both in the peritoneal tumors (2.5e9±2.498e9 %/ID/cc versus 1.6e10 ±1.3e10 %/ID/cc, respectively; p&amp;lt;0.05) and SC tumors (5.2e8 ±4.3e8 %/ID/cc versus 2.6e9 ±2.6e9 %/ID/cc; p&amp;lt;0.05). With a median survival of 35 days, all PBS treated mice died from disease between 21 to 47 days. In the CF33-hNIS-antiPDL1 treated group, the median survival was 49 days; and two out of eight mice were still alive at 220 days (p&amp;lt;0.05). These two surviving animals had no evidence of cancer; there was complete eradication of SC and peritoneal tumors. At one week after the first CF33-hNIS-antiPDL1 administration, significantly increased PET avidity for 124I uptake in the SC tumors (6.4±1.5 photons/second of regions of interest) and PC tumors (3.5±0.14 photons/second of regions of interest) were visible in the CF33-hNIS-antiPDL1 treated mice. Conclusion: After local SC tumor injection, CF33-hNIS-antiPDL1 can efficiently kill local tumor and kill distant peritoneal metastases to improve survival. Successful therapy of SC and peritoneal tumors using CF33-hNIS-antiPDL1 can be visualized by 124I-based PET imaging. Citation Format: Zhifang Zhang, Annie Yang, Shyambabu Chaurasiya, Sang-In Kim, Anthony K. Park, Jianming Lu, Susanne G. Warner, Yuman Fong, Yanghee Woo. Subcutaneous intratumoral administration of a novel oncolytic virus leads to eradication of peritoneal disseminated pancreatic cancer in nude 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 1155.
Abstract 2234: Detection of structural variation and analysis on HuKemia models by Using Bionano optical mapping
Authors: Xiaobo Chen, Huan Tian, Wubin Qian, Henry Q. Li, Sheng Guo
Journal: Cancer Research (2021)

Abstract Background: Genomic Structural variation (SV) refer to abnormalities in chromosome structure, is a normal part of variation in the human genome. Now Genomics SVs are recognized as the largest source of interindividual genetic variation and are closely associated with oncogenesis. The ability to identify constitutive and low-allelic fraction SVs is crucial. Standard SV detection method include chromosome banding, fluorescence in situ hybridization (FISH), and array comparative genome hybridization (CGH), which are manually intensive and have trouble finding low-frequency mutations. In recent year, genome physical mapping technologies have received increasing attention and optical mapping-based methods can well-accomplish sufficient to detect large size SVs or SVs within repetitive regions. Lately, Bionano optical mapping technology rapidly expanded its applications in the detection of structural variations. As well known, Acute Leukemia show distinct patterns of genetic aberrations including chromosome translocations, mutations, and aneuploidies in genes responsible for cell cycle regulation and lymphoid cell development. Method: We use our liver cancer model LI6671 to establish the Bionano Saphyr Gen2 genome imaging platform. DNA &amp;gt;100kbp is extracted, “CTTAAG” sequences were labelled across the entire genome by using Direct-Label-Enzyme (DLE) and linearized through chips for visualizations. Saphyr was loaded, linearized, and imaged labeled DNA in repeated cycles. Assembly Algorithms covert collected DNA images into constructing consensus genome maps. And this assay platform will be used to comprehensively identify SVs for studying our 21 HuKemia models. Results: By using this fluorescence labels distribution patterns, we find different structure variants among genome. We used filtered data for genome map assembly and compared with human genome hg38 for SV detection. In LI6671, we found out 3952 SVs in LI667 including 1166 deletion, 2497 insertion, 101 duplication, 78 inversion breakpoints, 66 interchr. translocation breakpoints and intrachr. translocation. Oncogenesis related SVs, such as a ~13Kb heterozygous deletion at KCNQ1 region, EPC1::SP1 gene fusions have be founded. Conclusion: Saphyr is a comprehensive platform, can discover a broad range of Genomic SVs and further improves our understanding of Acute Lymphocytic Leukemia (ALL) and Acute Myelocytic Leukemia (AML). Citation Format: Xiaobo Chen, Huan Tian, Wubin Qian, Henry Q. Li, Sheng Guo. Detection of structural variation and analysis on HuKemia models by Using Bionano optical mapping [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 2234.
Abstract 1750: Human <i>KIT</i>+myeloid cells facilitate visceral organ colonization by melanoma
Authors: Chun I. Yu, Jan Martinek, Te-Chia Wu, Kyung In Kim, Joshy George, Elaheh Ahmadzadeh, Rick Maser, Florentina Marches, Patrick Metang, Pierre Authie, Vanessa K. Oliveira, Victor G. Wang, Jeffrey H. Chuang, Paul Robson, Jacques Banchereau, Karolina Palucka
Journal: Cancer Research (2021)

Abstract Metastasis is a major risk factor for poor melanoma outcome, but mechanisms supporting distant organ colonization by melanoma are not fully understood. Here, we found that metastatic melanoma tumors from patients are infiltrated by CD33+ myeloid cells. To determine the role of CD33+ cells in melanoma metastasis, we used NSG mice humanized by engraftment of human CD34+ hematopoietic progenitor cells and transgenic expression of human hematopoietic cytokines SCF/GM-CSF/IL-3 (SGM3). Humanized (h)NSG-SGM3 mice enabled development of human CD33+ myeloid cells in the bone marrow and peripheral tissues, and when implanted subcutaneously with human melanoma cell line, supported melanoma colonization of the spleen, liver, lung, and kidneys. Melanoma growth in distant organs was dependent on host SGM3 expression and facilitated by human CD33+ myeloid cells. Deeper characterization attributed this activity to a rare human IL-3- and SCF-dependent CD33+CD11b+CD117+ progenitor cell subset comprising &amp;lt;4% of the total CD45+ leukocyte population. Metastatic tumor-infiltrating CD33+ cells from patients and hNSG-SGM3 mice showed converging transcriptional profiles. Single-cell RNAseq analysis identified a gene signature of a KIT/CD117 expressing CD33+ subset that correlated with decreased overall survival in TCGA melanoma samples. Thus, human CD33+CD11b+CD117+ myeloid cells facilitate metastatic colonization of distant organs by melanoma, representing a novel candidate biomarker as well as a therapeutic opportunity for metastatic melanoma. Citation Format: Chun I. Yu, Jan Martinek, Te-Chia Wu, Kyung In Kim, Joshy George, Elaheh Ahmadzadeh, Rick Maser, Florentina Marches, Patrick Metang, Pierre Authie, Vanessa K. Oliveira, Victor G. Wang, Jeffrey H. Chuang, Paul Robson, Jacques Banchereau, Karolina Palucka. Human KIT+myeloid cells facilitate visceral organ colonization by melanoma [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 1750.
Abstract 2223: Distinct genomic features of cutaneous, acral and mucosal melanomas in a Chinese retrospective cohort
Authors: Qiuyu Liu, Lingfei Kong, Weiran Wang, Danhua Wang, Tonghui Ma
Journal: Cancer Research (2021)

Abstract Background: The incidence of each subtype of melanoma in different races and ethnicities is significant differences. Cutaneous melanomas dominate in the Caucasian population. In contrast, melanomas that occur in the Chinese population are mainly arising from non-cutaneous tissue (extremities and mucous). Here, we reported an analysis of genomic features in 97 acral, 52 cutaneous and 18 mucosal melanomas. Methods: Patients (pts) with melanoma were enrolled, and surgical tumor tissues were collected. Mutation profiling was performed by next-generation sequencing (NGS). Results: Comparing to cutaneous melanoma patients (Age 53±11.6), acral (Age 65±11.1, P&amp;lt;0.001) and mucosal (Age 64±9.7, P=0.01) melanomas occurred in older Chinese patients. Mutations were identified in 148 of melanoma patients (88.62%), including 85 acral (87.63%), 47 cutaneous (90.38%) and 16 mucosal (88.89%) melanomas. Mutations of BRAF (25/52) in cutaneous melanoma, NRAS in acral melanoma (22/97) and mucosal melanomas (5/18) were observed as the most commonly genetic variations in different subtype of melanoma, which always occurred mutual exclusivity. Furthermore, focal amplification of 11q13 (CCND1 and FGF3/4/19) was all abundant in acral melanoma (11.34%, 11/97), which was reported to affect the efficacy of immunotherapy. In total, occurrence of BRAF, NRAS, CDKN2A mutations and 11q13 amplification were significantly different in cutaneous and non-cutaneous melanomas, which suggested different pathogenesis. Conclusions: In summary, genomic characterization of melanomas may offer insights into tumorigenesis and identify potential therapeutic targets in this disease. Citation Format: Qiuyu Liu, Lingfei Kong, Weiran Wang, Danhua Wang, Tonghui Ma. Distinct genomic features of cutaneous, acral and mucosal melanomas in a Chinese retrospective cohort [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 2223.
Rates and time trends in the consumption of breastmilk, formula, and animal milk by children younger than 2 years from 2000 to 2019: analysis of 113 countries
Authors: Paulo A R Neves, Juliana S Vaz, Fatima S Maia, Philip Baker, Giovanna Gatica-Domínguez, Ellen Piwoz, Nigel Rollins, Cesar G Victora
Journal: The Lancet Child & Adolescent Health (2021)
Evaluation of Residual Disease Positivity Rates in Adult Acute Lymphoblastic Leukemia Patients Treated with Asparaginase Versus Non-Asparaginase Containing Regimens
Authors: Sebastian Cerdena, Melissa C. Mackey, Maragatha Kuchibhatla, David A. Rizzieri, Meredith T. Moorman
Journal: Blood (2017)
Confronting High HIV Rates Among Transgender Women With Empowerment and Gender Affirmation
Authors: Bridget M. Kuehn
Journal: JAMA (2021)

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Abstract 471: Reference materials for tumor mutational burden transcriptome profiling
Authors: Matthew G. Butler, Yves Konigshofer, Jessica Dickens, Bharathi Anekella
Journal: Cancer Research (2021)

Abstract Immune Checkpoint Inhibitor (ICI) therapies continue to revolutionize treatment of advanced malignancies. However, identification of individuals who respond to ICI treatment remains challenging. Along with programmed death ligand 1(PD-L1 aka CD274) expression and microsatellite instability, tumor mutational burden (TMB), defined as the number of nonsynonymous mutations per megabase of genome, has emerged as a promising biomarker for differentiating responders from non-responders, especially in non-small cell lung cancer. Although promising, TMB is not a perfect biomarker for ICI efficacy with some individuals responding conversely to expectations. The imperfection of TMB as a prognostic biomarker may result from it being a proxy measurement of potential neoantigens. Indeed, all mutations that contribute to TMB will not be expressed as neoantigens and not all neoantigens will illicit immune responses. In refining ICI response prediction, tumor abundance of nonsynonymous mutations has aided in neoantigen prediction. In order to begin development of quality reference materials for neoantigen prediction, we have characterized the transcriptomes of four tumor cell lines that were previously used to formulate TMB reference materials. Sequencing libraries were prepared with the TruSeq Stranded Total RNA with Illumina Ribo-Zero Plus rRNA Depletion Kit and Invitrogen Collibri Stranded RNA Library Prep Kit from Illumina with Collibri H/M/R rRNA Depletion Kit. The resultant transcriptome libraries were sequenced on an Illumina NextSeq2000 platform and relative transcript counts were determined. Broad ranges of expression were observed among transcripts containing nonsynonymous mutations in each of the tumor cell lines tested. These datasets will serve as benchmarks for others attempting to combine TMB and tumor abundance in predicting neoantigen potential. Citation Format: Matthew G. Butler, Yves Konigshofer, Jessica Dickens, Bharathi Anekella. Reference materials for tumor mutational burden transcriptome profiling [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 471.
Gestational age recorded at delivery versus estimations using antenatal care data from the Electronic Maternal and Child Health Registry in the West Bank: a comparative analysis
Authors: Mervett Isbeih, Mahima Venkateswaran, Eatimad Abbas, Khadija Abu-Khader, Tamara Awwad, Mohammad Baniode, Buthaina Ghanem, Taghreed Hijaz, Asad Ramlawi, Rand Salman, Richard White, J Frederik Frøen
Journal: The Lancet (2021)
Abstract 13776: Pro-Inflammatory Small Low Density Lipoprotein-Like Particles in Patients With Severe Liver Disease
Authors: Shimpi Bedi, Erwin Garcia, Elias Jeyarajah, Irina Shalaurova, Maria Camila Perez-Matos, Esther Bullitt, Z. Gordon Jiang, James D Otvos, Margery A Connelly, Sean Davidson
Journal: Circulation (2019)

Background: Lipoprotein Z (LP-Z) are abnormal low-density lipoprotein (LDL)-like particles. These particles are elevated in subjects with cholestasis, but an in-depth analysis of these particles re...
Abstract 492: CNTN4 is a novel immune checkpoint protein that inhibits proliferation of T cell by interacting with APP
Authors: Mi Young Cha, Bu-Nam Jeon, Areum Jeong, Joo-Yeon Chung, Hyunsuk Yang, Kyung Mi Park, Hansoo Park
Journal: Cancer Research (2021)

Abstract Contactin 4 (CNTN4, alias BIG-2) is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as cell adhesion, playing a key role in maintaining the mechanical integrity and signaling properties of the synapse. However, its function and crosstalk with immune cells have not been investigated. Therefore, we tried to find out what role CNTN4 plays in cell adhesion between T cells and antigen-presenting cells (APC). CNTN4 has several binding partners such as the amyloid precursor protein (APP), amyloid-like protein 1 (APLP1), and protein tyrosine phosphatase receptor γ (PTPRγ). In previous papers, the APP was reported to be expressed in T cells. We investigated whether CNTN4 can bind to T cells. The degree of binding of CNTN4 to T cells varied depending on the expression level of APP, and that the binding between these two proteins was in the form of trans-binding. And it was confirmed that the direct binding is achieved through fibronectin 1~2 domain of CNTN4 and KPI (Kunitz protease inhibitor) domain of APP. Furthermore, we investigated whether CNTN4 has any effect on T cell proliferation. T cell proliferation and cytokine secretion assays by using CNTN4 recombinant protein showed that CNTN4 significantly inhibits proliferation and cytokine secretion (IL-2, IFN-γ, TNF-α) of T cells more than PD-L1. Although the expression of CNTN4 in immune cells has not yet been clearly confirmed, the expression of CNTN4 in various carcinomas have confirmed by using western, IHC, and bioinformatic data analysis. In particular, the higher the expression of CNTN4 in tumor tissues of gastric cancer patients, the worse the prognosis is in the survival curve. Our findings suggest that CNTN4 may behave as an immune checkpoint protein similar to other B7 family members. Further investigation of the CNTN4 signaling pathway and its receptors are warranted by our data and may lead to novel therapeutic interventions. Citation Format: Mi Young Cha, Bu-Nam Jeon, Areum Jeong, Joo-Yeon Chung, Hyunsuk Yang, Kyung Mi Park, Hansoo Park. CNTN4 is a novel immune checkpoint protein that inhibits proliferation of T cell by interacting with APP [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 492.
Reconsidering the American Joint Committee on Cancer Eighth Edition TNM Staging Manual Classifications for T2b and T3 NSCLC
Authors: Arvind Kumar, Sanjeevani Kumar, Shivee Gilja, Alexandra L. Potter, Vignesh Raman, Ashok Muniappan, Douglas Z. Liou, Chi-Fu Jeffrey Yang
Journal: Journal of Thoracic Oncology (2021)
Remdesivir Use and Hospital Length of Stay—The Paradox of a Clinical Trial vs Real-Life Use
Authors: Gio J. Baracco
Journal: JAMA Network Open (2021)

Michael E. Ohl, MD, MSPH; Donald R. Miller, ScD; Brian C. Lund, PharmD; Takaaki Kobayashi, MD; Kelly Richardson Miell, PhD; Brice F. Beck, MA; Bruce Alexander, PharmD; Kristina Crothers, MD; Mary S. Vaughan Sarrazin, PhD
Abstract 2369: Tumor-suppressive efficacy of let-7b microRNA against lung carcinogenesis is mediated by modulating the tumor microenvironment
Authors: Qi Zhang, Jing Pan, Donghai Xiong, Yian Wang, Mark S. Miller, Alberto Izzotti, Ming You
Journal: Cancer Research (2021)

Abstract Lung cancer is the leading cause of mortality worldwide. MicroRNAs (miRNAs) are potential candidates for lung cancer therapy. However, a major limitation is the lack of an efficient delivery system to directly deliver miRNA to cancer cells while limiting exposure to healthy cells. In our previous studies on aerosolized let-7b in lung cancer prevention, let-7b showed good inhibition of B[a]P-induced lung adenoma with no side effects. In this study, we found that aerosolized let-7b decreased tumor growth in the LKR13 (KRAS mutant) syngeneic mouse model. Let-7b post-transcriptionally suppresses PD-L1 and PD-1 expression in the tumor immune microenvironment, suggesting that let-7 microRNAs may promote antitumor immunity in vivo. Single cell RNA sequencing (scRNAseq) data showed that let-7b treatment decreased the expression of PD-1 in CD8+ T cells and reduced PD-L1 expression in lung tumor cells. Let-7b treatment also significantly changed the percentages of distinct CD8+ tumor-infiltrating lymphocytes (TIL) states. The proportion of CD8+ T cells mediating anti-tumor functions (EM-like CD8+ TILs) was increased significantly by let-7b treatment compared to control. In contrast, the CD8+ T cell subpopulation that has negative effects on anti-tumor immune response, exhausted CD8+ TILs, was significantly decreased by let-7b. Flow cytometry data showed that Let-7b treatment led to the accumulation of CD8+ T cells, granzyme B+ CD8+ T cells and IFN-γ+ CD8+ T cells in tumors, and a decrease of intratumoral Granulocyte-like myeloid derived suppressor cells (G-MDSC) cells. Our results suggest that the in vivo tumor-suppressive efficacy of let-7 is mediated, at least in part, by immune-promoting effects via down-regulating PD-L1 in tumors and/or PD-1 on CD8+ T cells. Citation Format: Qi Zhang, Jing Pan, Donghai Xiong, Yian Wang, Mark S. Miller, Alberto Izzotti, Ming You. Tumor-suppressive efficacy of let-7b microRNA against lung carcinogenesis is mediated by modulating the tumor microenvironment [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 2369.