tbuckley/cabot-search huggingface dataset:
Abstract 1927: Cancer cells induce apoptosis in hepatocytes as one of the mechanisms to displace hepatocytes in vessel co-opted colorectal cancer liver metastases
Authors: Miran Rada, Migmar Tsamchoe, Audrey Kapelanski-Lamoureux, Jessica Bloom, Stephanie Petrillo, Sébastien Tabariès, Diane H. Kim, Peter Younan, Alex Gregorieff, Peter Siegel, Anthoula Lazaris, Peter Metrakos
Journal: Cancer Research (2021)

Abstract Vessel co-option in colorectal cancer liver metastases (CRCLM) has been recognized as one of the mechanistic pathways of resistance against anti-angiogenic therapy. The cancer cells are highly motile in co-opted lesions, which move toward and along the pre-existing sinusoidal vessels and hijack them to gain access to nutrient. The movement of cancer cells is accompanied by displacement of the hepatocytes. However, the molecular mechanisms underlying this displacement are unclear yet. To examine whether apoptosis involved in hepatocytes displacement by cancer cells in co-opted lesions, we performed immunohistochemical staining for pro-apoptotic markers, such as cleaved caspase-3 and cleaved PARP-1. We observed overexpression of pro-apoptotic markers in liver parenchyma of co-opted lesions compared to angiogenic lesions, specifically the hepatocytes that are in close proximity to the cancer cells. In vitro, we found that culturing hepatocytes with either colorectal cancer cells or conditioned media of co-opted CRCLM organoids induces apoptosis. Importantly, our results also suggested proprotein convertase subtilisin/kexin type 9 (PCSK-9 or PC-9) as a potential mediator of cancer cells-driven hepatocytes apoptosis. Altogether, these results confirm that cancer cells exploit apoptosis to establish vessel co-option in CRCLM. Citation Format: Miran Rada, Migmar Tsamchoe, Audrey Kapelanski-Lamoureux, Jessica Bloom, Stephanie Petrillo, Sébastien Tabariès, Diane H. Kim, Peter Younan, Alex Gregorieff, Peter Siegel, Anthoula Lazaris, Peter Metrakos. Cancer cells induce apoptosis in hepatocytes as one of the mechanisms to displace hepatocytes in vessel co-opted colorectal cancer liver metastases [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 1927.
Sepsis after ureteroscopy: Development of a predictive model and prospective validation
Authors: D.E. Díaz Pérez, I. Laso Garcia, C. Sanchez Guerrero, G. Duque Ruiz, J. Lopez Plaza, A. Dominguez Gutierrez, C. Minguez Ojeda, M. Mata Alcaraz, S. Arribas Terradillos, M. Hevia Palacios, V. Gomez Dos Santos, F. Arias Funez, F.J. Burgos Revilla
Journal: European Urology (2021)
Abstract 2370: Tumor suppression potential of tRNA modification enzyme TruBs via let-7
Authors: Ryota Kurimoto, Hiroki Tsutsumi, Saki Ikeuchi, Hiroshi Asahara
Journal: Cancer Research (2021)

Abstract MicroRNA (miRNAs) let-7 is firstly discovered and widely involved in various tumors. Let-7 suppresses mRNAs of many oncogenes, such as KRAS and MYC. This, let-7 is strongly and selectively regulated by Lin28A/B. The let-7-Lin28A/B relationship could explain the pathogenesis of many tumors. However, the control mechanism of let-7, which cannot be explained by Lin28A/B alone, is reported. Furthermore, the regulatory mechanism of microRNAs by RNA-binding proteins such as Lin28 remains unclear. We have reported that TruB1, one of the tRNA modifying enzymes, specifically regulates let-7 by whole RNA binding protein screen (Kurimoto et al., EMBO J (2020)39:e104708). In this study, we evaluated in detail the effect of this TruB1-let-7 axis on the tumor phenotype. In addition to TruB1, another tRNA modifying enzyme TruB2 and other candidate RNA binding proteins were evaluated for its let-7 regulatory mechanism and tumor suppressive potential. We evaluated the effects of these candidates on cell proliferation and stemness in MTT assay, sphere formation assay and Xenograft model with knock down (KD) or over expression (in A549, HeLa or THP-1 cells). To elucidate that the phenotype was associated with let-7, we also use RNAi for let-7 families. We also checked the let-7-candidate proteins binding by RIP and eCLIP (enhanced version of the crosslinking and immunoprecipitation) analysis. Clinical effectiveness was assessed by public database (GEO and TCGA). In results, overexpression of TruB1 and other several genes suppressed the tumor growth and sphere formation ability in vitro with let-7 elevation. Interestingly, these suppressions were also seen in TruB enzymatic null mutants in TruBs (as we have reported in recently (Kurimoto et al., EMBO J (2020)39:e104708)). However, only TruB1 KD and one other candidate (gene A) KD showed the tendency to increase the tumor growth in vitro or in Xenograft model. The eCLIP and RIP analysis showed direct binding of TruB1 and gene A to let-7, but not TruB2 and others. In public database, only TruB1 and gene A strongly inversely correlated with several tumors. There was no relationship in TruB2 and tumor. These data introduced the novel players TruB1 and gene A to regulate the specific miRNA biogenesis and its impact on tumor phenotypes. Our data highlighted the potential of RNA binding protein independing on its known activity. Citation Format: Ryota Kurimoto, Hiroki Tsutsumi, Saki Ikeuchi, Hiroshi Asahara. Tumor suppression potential of tRNA modification enzyme TruBs via let-7 [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 2370.
Abstract 15550: Association Between N-3 Polyunsaturated Fatty Acid and Cognitive Function in Japanese Middle-Aged and Older Hypertensive Patients
Authors: Makoto Ikenoue, Yuichiro Yano, Manabu Hayakawa, Kazuyuki Shimada, Kazuomi Kario
Journal: Circulation (2011)

BACKGROUND High dietary intake of n-3 polyunsaturated fatty acid (n-3 PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been reported to be associated with better cogni...
Abstract 2162: Spatially resolved image-based transcriptomics using high-throughput single-molecule fluorescence in situ hybridization (HITSFISH)
Authors: Andrej Coleski, Sethu Pitchiaya, Jeremy D'Silva, Marcin Cieslik, Arul Chinnaiyan
Journal: Cancer Research (2021)

Abstract Single-cell transcriptomics enables the study of heterogeneity by uncovering the transcriptome of individual cells, which is averaged out in bulk analyses. This facilitates the grouping of cells based on similar transcriptomic profiles, potentially identifying cell subpopulations, such as rare tumor cells that mediate drug resistance or undergo metastasis. Image-based transcriptomic techniques can go a step further in uniquely profiling cells, by providing information about the spatial co-ordinates of transcripts and cells, whilst shedding light on cell morphology for phenotypic characterization. Single-molecule Fluorescence in situ hybridization (smFISH) is one image-based method in which fluorescently labeled tiling-oligonucleotide (TO) probes are bound along the length of complementary RNA strands, allowing for the detection of transcripts at nanometer-scale resolution. However, smFISH data analysis has been difficult to implement at scale due to the tradeoff between transcript resolution and imaging area, as well as the lack of automated feature detection tools. To address this issue, we have developed a pipeline called HIgh-Throughput Single-molecule FISH (HITSFISH), which uniquely combines smFISH with structured-illumination microscopy allowing for large-area high-resolution imagery with automated feature detection and analysis. We have validated our platform by showing high transcriptomic concordance between HITSFISH and other standard methods such as bulk RNA-seq and qPCR, demonstrating its ability to accurately measure RNA levels. With our pipeline we look to answer questions pertaining to the spatiotemporal landscape of gene expression within and across normal and cancerous cells. In addition, by using immunofluorescence in tandem with our platform, we can study transcript localization at various subcellular landmarks, such as membraneless organelles, to gain insight on subcellular mechanisms of gene regulation. Citation Format: Andrej Coleski, Sethu Pitchiaya, Jeremy D'Silva, Marcin Cieslik, Arul Chinnaiyan. Spatially resolved image-based transcriptomics using high-throughput single-molecule fluorescence in situ hybridization (HITSFISH) [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 2162.
Assessment of cortical parenchymal volume of the kidney by 3D processing of contrast-enhanced MSCT data before and after nephron-sparing surgery for kidney malignancy
Authors: A. Proskura, D.N. Fiev, M.M. Chernenky, K.B. Puzakov, A.D. Shpikina, D.V. Enikeev, P.V. Glybochko
Journal: European Urology (2021)
Abstract 1387: MET inhibition radiosensitizes KRAS-mutant rectal cancer
Authors: Antonio D'Ambrosio, Federica Verginelli, Francesca Orzan, Raffaella Albano, Elena Casanova, Paolo Luraghi, Francesca De Bacco, Andrea Bertotti, Livio Trusolino, Rebecca Senetta, Anna Sapino, Elena Del Mastro, Marco Gatti, Paolo M. Comoglio, Carla Boccaccio
Journal: Cancer Research (2021)

Abstract Rectal carcinoma, representing about a third of all newly diagnosed colorectal cancers, is one of the most common malignant tumors. The standard of care for locally advanced rectal cancer (LARC), consisting of neoadjuvant chemo/radiotherapy prior to surgical resection, is poorly effective, leading to complete tumor regression only in 10-30% of the cases. Approximately 40% of LARC harbor activating KRAS mutations, which have been extensively associated with primary resistance to targeted EGFR therapy and with radioresistance as well. Previous work showed that the MET receptor tyrosine kinase supports radioresistance and can be inhibited to radiosensitize tumor cell subpopulations retaining stem-like properties. Here, we show that LARC often express high levels of MET and can be successfully radiosensitized by MET inhibition. This was assessed in rectal stem-like cells isolated from human tumors (rectospheres), and transplanted in the mouse to regenerate tumors that faithfully reproduce the phenotype, the genotype and the therapeutic response of the original tumor. Mechanistically, we found that radioresistant KRAS-mutant rectospheres display significantly higher basal levels of RAD51, a master regulator of DNA homologous recombination repair, and increased RAD51 recruitment to irradiation-induced DNA double-strand breaks, as compared with KRAS-wild type rectospheres. Importantly, we showed that MET pharmacological inhibition by small-molecule kinase inhibitors, combined with radiotherapy, impairs RAD51 expression and function. This leads to DNA damage accumulation and results in effective radiosensitization of K-RAS-mutant rectal stem-like cells in vitro and in vivo, and significant inhibition of experimental tumors. Therefore, preclinical evidence is provided that MET can be exploited as a therapeutic target to radiosensitize KRAS-mutant rectal cancer at stem-like cell level. Citation Format: Antonio D'Ambrosio, Federica Verginelli, Francesca Orzan, Raffaella Albano, Elena Casanova, Paolo Luraghi, Francesca De Bacco, Andrea Bertotti, Livio Trusolino, Rebecca Senetta, Anna Sapino, Elena Del Mastro, Marco Gatti, Paolo M. Comoglio, Carla Boccaccio. MET inhibition radiosensitizes KRAS-mutant rectal 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 1387.
Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial
Authors: Valentin Mocanu, Zhengxiao Zhang, Edward C. Deehan, Dina H. Kao, Naomi Hotte, Shahzeer Karmali, Daniel W. Birch, Kalutota K. Samarasinghe, Jens Walter, Karen L. Madsen
Journal: Nature Medicine (2021)
COPD prevalence in chronic heart failure
Authors: Armine Minasian, Richard Dekhuijzen, Frank Van den Elshout, Petra Vos, Frank Willems, Paul Van den Bergh, Yvonne Heijdra
Journal: European Respiratory Journal (2011)

Introduction: COPD frequently coexists with chronic heart failure (CHF) leading to impaired prognosis as well as diagnostic and therapeutic challenges. However, lungfunctional data on COPD prevalence in CHF are scarce and COPD remains to be widely undiagnosed or misdiagnosed. The aim of this study was to determine COPD prevalence in CHF.

Methods: In this cross-sectional study spirometry was performed in 220 CHF patients (78.2% male, median age 71 years [IQR 63-77] with left ventricular ejection fraction < 40% recruited from the outpatient cardiology department in two hospitals in The Netherlands. COPD was determined according to GOLD criteria (post-bronchodilator FEV1/FVC < 70%).

Results: COPD was found by spirometry in 81 patients (36.8%). The majority had mild to moderate COPD (GOLD I/II 88.9%). Of these patients only 42 (51.9%) were known with a history of obstructive lung disease, whereas 39 (48.1%) had newly diagnosed COPD. By dividing the whole study population into groups of patients with and without a history of obstructive lung disease (n = 58 and n = 162 respectively), we found overdiagnosis of COPD in the first group (n = 16, 27.6%) and underdiagnosis of COPD in the latter group (n = 39, 24.1%) based on spirometry.

Conclusion: COPD is a frequent co-morbidity in CHF with left ventricular systolic dysfunction, but is often unrecognized or even overdiagnosed. To avoid this and thus ensure adequate treatment of COPD in CHF, pulmonary function tests should be routinely obtained, preferably in a stable state of heart failure.
Incorporating fatty liver disease in multidisciplinary care and novel clinical trial designs for patients with metabolic diseases
Authors: Mohammed Eslam, Aijaz Ahmed, Jean-Pierre Després, Vivekanand Jha, Jason C G Halford, Jack Tan Wei Chieh, David C H Harris, Masaomi Nangaku, Stephen Colagiuri, Giovanni Targher, Shashank Joshi, Christopher D Byrne, Kamlesh Khunti, Mindie H Nguyen, Robert G Gish, Jacob George
Journal: The Lancet. Gastroenterology & hepatology (2021)
The efficacy and safety of relugolix compared to degarelix in advanced prostate cancer patients: A network meta-analysis of randomized trials
Authors: R. Sari Motlagh, M. Abufaraj, K. Mori, A. Aydh, P. Rajwa, S. Katayama, N.C. Grossmann, E. Laukhtina, H. Mostafai, B. Pradere, F. Quhal, P.I. Karakiewicz, D.V. Enikeev, S.F. Shariat
Journal: European Urology (2021)
Abstract 659: Evaluation of homologous recombination repair related gene mutation on survival and drug response in Chinese epithelial ovarian cancer patients
Authors: Lei Li, Kang Shao, Jianwei Zhang, Meng Liu, Kui Wu, Ming Wu
Journal: Cancer Research (2021)

Abstract Background: Target sequencing of epithelial ovarian cancer (EOC) has been widely used in clinical to detect the status of BRCA1/2 and genes in homologous recombination repair (HRR) pathway. But there still lacks of systematic evaluation of HRR related gene mutation effect on clinical outcome. Methods: Totally 230 EOC patient is recruited and received OseqT panel sequencing including 12 HRR related genes, 5 mismatch repair related genes and 8 ovarian cancer related genes. All the patients received platinum-based chemotherapy. 25 of them received PARP inhibitor therapy. Their responses to the therapy, OS and PFS were collected for analysis. Results: We found that BRCA2 and BRCA1/2 mutation carriers (somatic and germline) had longer OS (p value: 0.016 and 0.028) and PFS (p value: 0.002, 0.006) than non-carriers, PTEN and MSH2 germline mutation carriers had longer PFS (p value: 0.038, 0.049) than non-carries. When we compared germline pathogenic carriers and non-pathogenic carriers on OS and PFS, there is significant difference in PALB2 (p value: 0.036, 0.015) and STK11 (0.001, 0.018), BRCA1 mutation did not affect survival time in both OS and PFS. Then we observed the response to platinum-based chemotherapy. We found that the carriers of germline pathogenic variants in BRCA1, BRCA1/2 and HRR related genes were significant related with better response (p value: 0.16, 0.042 and 0.048), If we combined germline and somatic pathogenic variants together, the p value of BRCA1, BRCA1/2 and HRR related genes were changed to 0.001, 0.009 and 0.001. Somatic status of those gene alone had no relationship with chemotherapy response.In the patients received treatment of PARP inhibitor Niraparib, carriers of germline and somatic pathogenic variant in BRCA1 and BRCA1/2 were more sensitive to Niraparib (p value: 0.18, 0.008), There was only 1 BRCA2 pathogenic carrier and no other HRR related gene pathogenic carrier in 25 patients. So, the sensitivity of BRCA2 and HRR-related gene mutation carriers were not calculated. Conclusions: In our cohort, BRCA2 and BRCA1/2 mutation carriers had longer OS and PFS than non-carriers. PTEN, MSH2, PALB2 and STK11 mutation status also had relationship with survival in some circumstances, BRCA1, BRCA1/2 and HRR-related genes could all be used to predict drug sensitivity, germline and somatic variant should be combined used to reach better performance. Citation Format: Lei Li, Kang Shao, Jianwei Zhang, Meng Liu, Kui Wu, Ming Wu. Evaluation of homologous recombination repair related gene mutation on survival and drug response in Chinese epithelial ovarian cancer patients [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 659.
The learning curve of prostate MRI/TRUS target fusion biopsy after more than 1000 procedures: Residents’ experience
Authors: E. Checcucci, F. Piramide, S. De Cillis, D. Amparore, G. Volpi, A. Piana, S. Granato, A. Pecoraro, P. Alessio, B. Carbonaro, J. Meziere, G. Cattaneo, F. Ragni, M. Manfredi, C. Fiori, F. Porpiglia
Journal: European Urology (2021)
Prostate cancer screening using prostate-specific antigen, a multiplex blood-test, magnetic resonance imaging and targeted prostate biopsies: The STHLM3MRI trial
Authors: T. Nordström, A. Discacciati, M. Bergman, M. Aly, M. Annerstedt, A. Glaessgen, S. Carlsson, F. Jäderling, M. Eklund, H. Grönberg
Journal: European Urology (2021)
The 17-gene Genomic Prostate Score® assay as a predictor of biochemical recurrence in men with intermediate- and high-risk prostate cancer
Authors: B.T. Helfand, M. Paterakos, C-H. Wang, P. Talaty, J. Abran, J.P. Bennett, D.W. Hall, T. Aboushwareb
Journal: European Urology (2021)
Clinical Impact of the Predict Prostate Risk Communication Tool in Men Newly Diagnosed with Nonmetastatic Prostate Cancer: A Multicentre Randomised Controlled Trial
Authors: David Thurtle, Val Jenkins, Alex Freeman, Mike Pearson, Gabriel Recchia, Priya Tamer, Kelly Leonard, Paul Pharoah, Jonathan Aning, Sanjeev Madaan, Chee Goh, Serena Hilman, Stuart McCracken, Petre Cristian Ilie, Henry Lazarowicz, Vincent Gnanapragasam
Journal: European Urology (2021)
A Stranger to Silence
Authors: Arjun V. K. Sharma
Journal: JAMA (2021)

A Stranger to SilenceJust over a year ago, the world fell into silence.A silence deeper than most have ever known.The quiet was so profound during periods of global lockdown, scientists measured it to the core of the earth. 1 And I felt it all in my head.Blood bangs off the misshapen walls in the veins of my neck; this pinballing generates the venous hum that is the root of my condition.Although it is a sound I first learned many years ago, it worsened considerably at the beginning of the pandemic when I fell ill in New York City.At the time, there was a scarcity of COVID-19 tests to prove my symptoms otherwise.But my suspicions were confirmed when I came to understand tinnitus as one of the symptoms that lingers (or worsens) in the aftermath of the virus. 2 As a person with tinnitus, I hear a singular note that filters above the others around me.It is a sound without a true auditory stimulus; it comes, unnervingly, from everywhere and nowhere.The sound also carries with it the individuality of a thumbprint.When my mind believes it is not listening to what sounds like ice scratching against a metal tray or the clicking at the end of a record, it might hear a high-pitched hiss.Like when you bring your ear up close to a punctured tire, only, imagine that tire with an endless supply of air.
Abstract 1794: Human cancer associated fibroblast subsets can differentially regulate immunotherapy response in head and neck cancer patients
Authors: Diana Graves, Michael J. Korrer, Aleksandar Z. Obradovic, Sohini Roy, Andrea Califano, Charles G. Drake, Young J. Kim
Journal: Cancer Research (2021)

Abstract The stromal cancer associated fibroblasts (CAF) have been postulated to modulate immune responses, but their role in clinical immunotherapy has not been rigorously explored in detail. To determine potential biomarkers of response and resistance for αPD-1 therapy in head &amp; neck cancer patients, we performed high dimensional immunophenotyping to include single cell RNA sequencing (scRNA-SEQ) from a neoadjuvant trial of 50 advanced-stage head and neck squamous cell carcinoma (HNSCC) patients that were treated with nivolumab. Sufficient suspension cells from the tumors harvested pre and post nivolumab treatment allowed single-cell RNA sequencing on 4 patients as well as bulk RNA sequencing on 40 patients. Using the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) and Virtual Inference of Protein-activity by Enriched Regulon (VIPER) bioinformatic analysis platform on the matched scRNA-Seq dataset to capture low expressing genes such as transcription factors, we identified 14 distinct cell types present in HNSCC patients. While CD8 T cells did not show increased number among the responder cohort, T cell cluster analysis showed enhanced IFNγ, granzyme, and perforin. Of these 14 cell types, the CAF cluster showed significant changes among the nivolumab responder cohort. Upon deeper analysis of this fibroblast population, we identified 5 distinct clusters of cancer associated fibroblast subsets (CAF-A, B, C, D, and E) of which, one cluster, CAF-A correlated with patient response to αPD-1 therapy. In order to determine the significance of this CAF subset's function, we isolated CD45-EpCAM-CD31-CD29+FAP+ CAF-A's from primary HNSCC tumor specimens and co-cultured with primary human T cells. Analysis by flow cytometry showed that CAF-A suppresses both CD4+ and CD8+ T cell proliferation as well as activation of these T cells. When we queried the cancer genome atlas, CAF-A gene signature correlated with increased survival, corroborating the important regulatory role of these CAF subsets in the context of endogenous immune responses. Overall, our findings demonstrate the functional importance of CAF subsets in modulating the immunoregulatory milieu of the human HNSCC for the first time, and justifies a more in depth characterization of these stromal cells in human squamous carcinoma in the current era of cancer immunotherapy. Citation Format: Diana Graves, Michael J. Korrer, Aleksandar Z. Obradovic, Sohini Roy, Andrea Califano, Charles G. Drake, Young J. Kim. Human cancer associated fibroblast subsets can differentially regulate immunotherapy response in head and neck cancer patients [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 1794.