tbuckley/cabot-search huggingface dataset:
Abstract 734: Macrophage tumor cell metabolic interactions induce therapeutic resistance in prostate cancer
Authors: Asmaa El-Kenawi, William Dominguez Viqueira, Min Liu, Shivanshu Awasthi, Jasreman Dhillon, Kosj Yamoah, Xiaoqing Yu, John Koomen, Robert Gatenby, Brian Ruffell
Journal: Cancer Research (2021)

Abstract Castration-resistant prostate cancer (CRPC) is a lethal stage of disease. A wealth of clinical and experimental data supports the persistence of androgen receptor (AR) signaling in many cases of CRPC, despite androgen-deprivation therapy (ADT). Here we sought to determine the role of macrophage cholesterol in CRPC and androgen signaling using a syngeneic model that reflected the mutational landscape of the disease. A transcriptomic analysis of prostate tumors following macrophage depletion revealed lower molecular signatures for steroid and bile acid metabolism, indicating perturbation of cholesterol transport. Since cholesterol is the precursor of steroid hormones, we reasoned that macrophages were regulating androgen biosynthesis within the prostate tumor microenvironment. Indeed, macrophage depletion reduced the levels of androgens within prostate tumors and restricted androgen receptor (AR) nuclear localization in vitro and in vivo. Macrophages were cholesterol rich and had the ability to transfer cholesterol to tumor cells in vitro, and AR nuclear translocation was inhibited by activation of Liver X Receptor (LXR)-β, the master regulator of cholesterol homeostasis. Finally, combining macrophage depletion with androgen deprivation therapy increased survival, supporting the therapeutic potential of targeting macrophages in CRPC. Citation Format: Asmaa El-Kenawi, William Dominguez Viqueira, Min Liu, Shivanshu Awasthi, Jasreman Dhillon, Kosj Yamoah, Xiaoqing Yu, John Koomen, Robert Gatenby, Brian Ruffell. Macrophage tumor cell metabolic interactions induce therapeutic resistance in prostate 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 734.
Abstract 2726: Characterization of immune microenvironment and heterogeneity in breast cancer subtypes
Authors: Drashti Jain, Linda Liao, Megan Hopkins, Mary Anne Quintayo, Vida Talebian, Jane Bayani, Alison Cheung, Martin Yaffe, John Bartlett, Melanie Spears
Journal: Cancer Research (2021)

Abstract Despite ongoing advancements in the clinical management of breast cancer (BC), the variability in the response to treatment requires continued understanding of the molecular biology of this disease. Receptor status for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) along with pathological features dictate the course of therapy. Tumor cells in BC are phenotypically diverse between and within patients due to underlying differences in their cellular biology. This heterogeneity in the expression of key molecular targets renders some tumor cells resistant to therapy. While the etiology of intra-tumor heterogeneity is under investigation, it is equally important to characterize the heterogeneous nature of the tumor microenvironment as both of these compartments are engaged in the molecular crosstalk; with the latter known to contribute to tumor progression. Traditionally considered to be immunologically cold, recent advances have demonstrated that some BC subtypes elicit immunological response. However, further research is warranted to broadly illustrate the immune cell contexture in BC in a spatial context. In this study, the immune microenvironment was characterized through proteomic analysis using NanoString's GeoMX Digital Spatial Profiling (DSP) platform, in a cohort of early BC patients. This cohort consists of Luminal A, Luminal B, Basal, and HER2 BC subtypes. Correlation of proteomic and genomic data will reveal the role of genomic alterations in differential immune response. Protein markers were analyzed in both the tumor microenvironment (TME) and tumor compartments with beta-2-microglobulin, CD40, and CD11 significantly expressed in the TME compartment while PanCK, ERalpha, and HER2 were enriched in the tumor. Interestingly, CD127 was also expressed in the tumor compartment, indicating infiltration by memory T cells. Through this study we spatially characterize the immune microenvironment in BC subtypes, providing further evidence against the “immunologically cold” view of this disease. In addition, we demonstrate the potential clinical use of this novel platform in diagnosing and better stratifying BC patients based on spatial heterogeneity in tumor and TME. Citation Format: Drashti Jain, Linda Liao, Megan Hopkins, Mary Anne Quintayo, Vida Talebian, Jane Bayani, Alison Cheung, Martin Yaffe, John Bartlett, Melanie Spears. Characterization of immune microenvironment and heterogeneity in breast cancer subtypes [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 2726.
Abstract 2288: Identification of gene fusions in soft tissue sarcoma improved by integrative DNA and RNA sequencing
Authors: Jiayong Liu, Shu Li, Tian Gao, Chunyang Wang, Qifan He, Xiaojuan Wang, Tonghui Ma
Journal: Cancer Research (2021)

Abstract Background: More than 50 different histologic subtypes of soft tissue sarcoma (STS) with mesenchymal origin have been recognized, and their overlapping morphology and histology make clinical diagnosis challenging. Gene fusion has been described as an important molecular biological feature of STS, which can assist in its diagnosis and treatment. Conventional DNAseq methods have limitations for gene fusion detection, while the RNAseq method might circumvent them. In this study, we evaluated the clinical value of integrated DNA and RNA sequencing in the detection of STS gene fusions. Methods: Formalin-fixed and paraffin embedded (FFPE) tumor samples and matched blood of 142 Chinese STS patients were collected and tested by the next-generation sequencing (NGS)-based 825-gene DNA panel and 395-gene RNA panel at Genetronhealth, a laboratory accredited by College of American Pathologists and Clinical Laboratory Improvement Amendments. Results: The genetic landscape of 75 male and 67 female Chinese patients with STS was analyzed. The median age of enrolled patients was 39 years (range, 1-82 years). Multiple histological subtypes were collected, including rhabdomyosarcoma (n = 15), liposarcoma (n = 15), myofibroblastic sarcoma (n = 11) and other types which were all less than 10 cases. Overall, 83 different fusions were detected in 60 patients. Of these, 25 fusions could be detected both by DNA and RNA panels in 18 patients, five fusions were detected only by the DNA panel in four patients, and 53 fusions only by the RNA panel in 39 patients. Compared to DNA-NGS individual testing, integrative panels increased the detection rate of fusion in patients with STS by 177% (53/30). The five gene fusions detected only by the DNA panel, including FOSL1-RELA, intergenic-RUNX2, ADAMTS16-TERT, NCR3LG1-KMT2A and YAP1-MAMLD1, remain clinical significance uncertain in STS. Fusion genes, such as PAX3-FOXO1, ASPSCR1-TFE3, COL1A1-PDGFB, EWSR1-ERG, were detected separately by the RNA panel, which could assist the diagnosis or targeted therapy. Additionally, unreported DIP2B-EWSR1 and AMLD1-SSX1 gene fusions were detected in a patient with clear cell sarcoma and a patient with synovial sarcoma respectively, which might be helpful in clinical diagnosis. Conclusions: Our results showed that the integrated DNA and RNA sequencing can effectively improve the detection rate of STS gene fusions, which might benefit more STS patients. Citation Format: Jiayong Liu, Shu Li, Tian Gao, Chunyang Wang, Qifan He, Xiaojuan Wang, Tonghui Ma. Identification of gene fusions in soft tissue sarcoma improved by integrative DNA and RNA sequencing [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 2288.
연구논문 : Fitz-Hugh-Curtis 증후군의 임상양상: 25예의 분석
Authors: 양현웅 ( Hyeon Woong Yang ), 정성희 ( Sung Hee Jung ), 한현영 ( Hyun Young Han ), 김안나 ( An Na Kim ), 이윤정 ( Yun Jung Lee ), 차상우 ( Sang Woo Cha ), 고훈 ( Hun Go ), 최기영 ( Gi Young Choi ), 조성훈 ( Soung Hoon Cho ), 임신형 ( Sin Hyung Lim )
Journal: Clinical and Molecular Hepatology (2008)
Abstract 176: Detecting neoepitopes from tumor RNA sequencing datasets
Authors: Drew Thompson, Olena M. Vaske, Arjun Rao, Holly C. Beale
Journal: Cancer Research (2021)

Abstract Epitopes are peptides that present on the surface of the cell and can be recognized by immune cells to initiate the immune response. Identification of neoepitopes – tumor-specific, MHC-bound epitopes recognized specifically by T-cells – is valuable for predicting response to immunotherapies, including checkpoint blockade therapies. Tumors with more neoepitopes tend to be more responsive to immune checkpoint therapies compared to tumors with fewer neoepitopes. ProTECT is a previously published computational method that uses Illumina whole genome and transcriptome sequencing data from tumor and matched normal tissues to identify neoepitopes. Tumor and normal whole genome sequencing data are used to infer a patient's HLA haplotypes, as well as annotate variants as either somatic or germline. While whole genome sequencing is comprehensive, it is quite costly and not available for many samples. Here we adapt ProTECT to use only tumor RNA sequencing data and HLA haplotype information available to the clinician to identify neoepitopes in a tumor sample. Prior to running ProTECT, we use the computational tools Opossum and Platypus for variant calling instead of Radia (which is designed for variant calling using both RNA and DNA sequencing data as input). To determine which variants are somatic and therefore could represent tumor neoepitopes, variants found in RNA are compared to a panel of normals, for example the Genome Aggregation Database (gnomAD; containing variants from 125,748 exome sequences and 15,708 whole-genome sequences). With the resulting somatic variants and the HLA type, ProTECT proceeds as usual, with translation of variants into proteins, MHC:Peptide binding predictions and neoepitope ranking. We find that high quality neoepitopes are identifiable using an RNA-only approach, when genomic data is absent. Future work will validate the sensitivity of our method by benchmarking it against the original ProTECT predictions in the TCGA Prostate Adenocarcinoma cohort. Citation Format: Drew Thompson, Olena M. Vaske, Arjun Rao, Holly C. Beale. Detecting neoepitopes from tumor RNA sequencing datasets [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 176.
Mesenteric Inflammatory Myofibroblastic Tumor on 68Ga-FAPI PET/CT
Authors: Huipan Liu, Xiao Yang, Dongmei Fan, Taiyong Lv, Yue Chen
Journal: Clinical Nuclear Medicine (2021)

Inflammatory myofibroblastic tumor is an uncommon mesenchymal neoplasm, which can be seen in any anatomic region from the central nervous system to the gastrointestinal tract. Herein, we report the 68Ga-FAPI PET/CT findings in a 49-year-old man with mesenteric inflammatory myofibroblastic tumor.
Low-dose targeted radionuclide therapy renders immunologically cold tumors responsive to immune checkpoint blockade
Authors: Ravi B. Patel, Reinier Hernandez, Peter Carlson, Joseph Grudzinski, Amber M. Bates, Justin C. Jagodinsky, Amy Erbe, Ian R. Marsh, Ian Arthur, Eduardo Aluicio-Sarduy, Raghava N. Sriramaneni, Won Jong Jin, Christopher Massey, Alexander L. Rakhmilevich, David Vail, Johnathan W. Engle, Trang Le, KyungMann Kim, Bryan Bednarz, Paul M. Sondel, Jamey Weichert, Zachary S. Morris
Journal: Science Translational Medicine (2021)

Low-dose targeted radionuclide therapy combined with immune checkpoint inhibition enhances complete response rates in preclinical tumor models.
Abstract 1856: Donor and antibody diversity in NK cell-mediated antibody dependent cellular cytotoxicity (ADCC) detected using an optimized multiplexed assay and advanced flow cytometry
Authors: Julie Lovchik, Mark Carter
Journal: Cancer Research (2021)

Abstract Tumor-specific monoclonal antibodies (mAb) which induce NK cell-mediated antibody dependent cellular cytotoxicity (ADCC) have proven to be successful against several types of cancer. Evaluating the potency of a new, tumor-specific mAb requires testing with multiple sources of donor cells since the degree of NK cell-mediated ADCC is known to be variable between patients. Thus, in addition to evaluating whether a new tumor-specific mAb can effectively induce NK cell-mediated ADCC, it is also important to characterize the donor NK cells utilized in order to provide insight into potential treatment efficacy. In the current study, we investigated the application of a novel, high throughput assay in assessing the ADCC potency of different anti-hCD20 mAbs against a Burkitt's lymphoma cell line using effector cells obtained from multiple donors. This multiplexed assay incorporates a cells and beads format to enable the simultaneous measurement of target cell killing, along with enumeration and phenotyping of the NK cells, and quantification of up to 8 secreted effector proteins and cytokines. The assay requires a sample volume of just 10 µl and can be performed in a single well of a 96 or 384 well plate using the iQue® platform for advanced flow cytometry. Data analysis and visualization was done using the integrated iQue Forecyt® software package. The results showed a mAb concentration-dependent increase in tumor cell killing, along with corresponding increases in secretion of Granzyme B and CD178 (Fas Ligand), and production of IFNγ, TNF, and RANTES. The degree of NK cell-mediated ADCC and effector protein secretion levels were dependent on both the anti-hCD20 mAb and donor cells used, with higher levels of ADCC and effector protein secretion observed using a non-fucosylated anti-hCD20 mAb as compared to a conventional, fucosylated anti-hCD20 mAb. This method enabled the rapid assessment of the potency of different mAbs in ADCC mediated by NK cells, and also effectively distinguished potential differences in mAb efficacy between donors. Citation Format: Julie Lovchik, Mark Carter. Donor and antibody diversity in NK cell-mediated antibody dependent cellular cytotoxicity (ADCC) detected using an optimized multiplexed assay and advanced flow cytometry [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 1856.
Abstract 1246: Anticancer activitiy of indolo[2,3-c]quinoline stabilization of the KRAS promoter G4mid structure
Authors: Alexandra Maria Psaras, Jared Miller, L. Nathan Tumey, Tracy A. Brooks
Journal: Cancer Research (2021)

Abstract KRAS is a well validated anti-cancer therapeutic target; many active drug discovery programs are ongoing with foci on individual mutant isoforms, necessitating a wide array of drugs to be developed and missing cancers with dysregulation of non-mutant KRAS. Transcriptional down-regulation has been demonstrated to be lethal to tumor cells with aberrant KRAS signaling, irrespective of mutational status, and to potentially have a wide therapeutic window. G-quadruplex (G4) formation within KRAS's core promoter offers a molecular target to decrease the gene expression. Targeted G4-stabilization within the KRAS promoter targets cancer cells' acquired addiction to the transforming event of aberrant KRAS signaling through an activating mutation or protein overexpression, and thus is applicable to both of these deviant states. Small molecules that specifically inhibit transcriptional expression of KRAS genes have great potential for patients whose tumors have disregulated KRAS function. In the current works, compounds clarify the physiologically relevant G4 within the KRAS promoter (G4mid) through a combination of ex vivo screening, luciferase, cytotoxicity, and transcriptional regulation assays. A small set of novel indolo[2,3-c]quinoline compounds were synthesized and a newly optimized FRET Melt2 assay with a Z' score of &amp;gt;0.5 was used to determine KRAS G4mid stabilization efficacy and selectivity. Compounds were then examined for KRAS promoter stabilization using a luciferase assay, pancreatic and ovarian cancer cytotoxicity by an MTS assay, and correlative changes in KRAS transcription as measured by multiplexed qPCR. JM-222 is the lead indolo[2,3-c]quinoline compound that demonstrates KRAS G4mid selective stabilization and promoter regulation, cancer cell cytotoxicity and altered KRAS transcription. These works highlight the function of G4mid in regulating KRAS transcription, novel synthetic methods for indolo[2,3-c]quinoline synthesis, the improved utility of the FRET Melt2 assay, and the overall potential for small compound-mediated KRAS promoter G4 stabilization for patients harboring tumors with aberrant KRAS signaling. Citation Format: Alexandra Maria Psaras, Jared Miller, L. Nathan Tumey, Tracy A. Brooks. Anticancer activitiy of indolo[2,3-c]quinoline stabilization of the KRAS promoter G4mid structure [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 1246.
The safety and efficacy of botulinum toxin type A treatment in neurogenic detrusor overactivity and idiopathic overactive bladder: A systematic review and meta-analysis of prospective, randomized, double-blinded, placebo-controlled clinical trials
Authors: A. Bijnens, L.J.M. Bijnens, G.A. Van Koeveringe, D.M.J. Vrijens
Journal: European Urology (2021)
Covid-19 cough: use all your senses to make a diagnosis
Authors: Arnold G Zermansky
Journal: BMJ (2021)

Your "cough in a box" item 1 reminded me of my first experience of general practice as a student over 50 years ago.Between patients we heard a child coughing in the waiting room.My tutor said, "That kid's got measles."In time, the child appeared and had Koplik spots on the buccal mucosa.There followed a discussion on how to recognise different illnesses by the timbre and periodicity and accompaniments of cough.Half a decade later, while working for the Covid Clinical Advisory Service of NHS 111, I soon began to recognise covid by the characteristic cough, and distinguish it from the high pitched, unstopping whooping cough; the fruity bronchitis; the breathy, bubbly heart failure; the brassy cough of lung cancer; and the half cough of asthma.I still remember the hard, moist measles cough-though, thanks to immunisation, I haven't heard if for over 30 years.Using all your senses to make a diagnosis is a valuable lesson I carried with me throughout my career and passed on to my trainees-I still use it on the bus.
Abstract 251: Data distribution for easy pancancer analysis
Authors: Caleb M. Lindgren, Chelsie Minor, Lindsey K. Olsen, Brittany Henderson, CPTAC Investigators, Samuel H. Payne
Journal: Cancer Research (2021)

Abstract A growing number of datasets characterize tumors with quantitative proteomic and genomic data. These emerging datasets are typically specific to a single cancer type. However, analysis of proteogenomic patterns across multiple cancer types allows us to identify common mechanisms in the function of cancer, as well as mechanisms that are unique to specific cancer types. Here we present how a Python data API from the NCI's CPTAC program bridges the gap between different cancer datasets to facilitate pancancer analysis. While we have previously presented this API as a general model for data dissemination, we have yet to display the specific pancancer applications of the tool. Several key aspects of its design optimize its use from a pancancer point of view, including parsing data to a single consistent format for all datasets, and automatically managed data updates for each dataset. Our analyses demonstrate the efficacy of our data model for generalizing an analysis pipeline, applying it to multiple cancer types, and comparing the results. This enables unique discoveries that characterize the overall proteogenomic landscape of cancer. Citation Format: Caleb M. Lindgren, Chelsie Minor, Lindsey K. Olsen, Brittany Henderson, CPTAC Investigators, Samuel H. Payne. Data distribution for easy pancancer analysis [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 251.
MRI-guided transurethral ultrasound ablation for treatment of benign prostatic obstruction
Authors: M.H.J. Anttinen, A. Viitala, P. Mäkelä, J. Saunavaara, V. Suomi, T. Sainio, R. Blanco Sequeiros, P. Taimen, P.J. Boström
Journal: European Urology (2021)
Prognostic significance of radiologic infiltrative feature of primary renal tumor in metastatic renal cell carcinoma
Authors: H. Tanaka, Y. Yamaguchi, S. Fukuda, H. Fukushima, S. Uehara, Y. Yasuda, S. Yoshida, M. Yokoyama, Y. Matsuoka, S.C. Campbell, Y. Fujii
Journal: European Urology (2021)
Abstract 3013: Orthotopic patient-derived xenografts (O-PDX) are effective precision oncology models that can predict therapeutic response, recurrence, and acquired drug resistance
Authors: Jonathan Nakashima, Jantzen Sperry, Bianca Carapia, Deborah Yan, Angelina Chin, Aliakbar Shahsafaei, Joan Chen, Yuan-Hung Chien, Christophe Pedros, Noah Federman, Arun Singh, Fritz C. Eilber, Brian Datnow
Journal: Cancer Research (2021)

Abstract Patient-derived xenografts provide a functional test system in a living organism, making them the leading assay for precision oncology and drug development. In vivo pharmacology studies are widely performed using subcutaneous implantation; however, due to significant changes in the tumor microenvironment, this methodology falls short of modeling the full complexities of human cancer. We use quantitative magnetic resonance imaging (MRI) to report differences in growth kinetics and pharmacological response between orthotopic and subcutaneous implantation of patient-derived xenografts. We demonstrate that O-PDX models can predict effective treatment strategies for individual patients and forecast tumor recurrence after therapy. Furthermore, we use this approach to develop in vivo models of acquired drug resistance to strategize future treatment options and aid in drug development. Citation Format: Jonathan Nakashima, Jantzen Sperry, Bianca Carapia, Deborah Yan, Angelina Chin, Aliakbar Shahsafaei, Joan Chen, Yuan-Hung Chien, Christophe Pedros, Noah Federman, Arun Singh, Fritz C. Eilber, Brian Datnow. Orthotopic patient-derived xenografts (O-PDX) are effective precision oncology models that can predict therapeutic response, recurrence, and acquired drug resistance [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 3013.