tbuckley/cabot-search huggingface dataset:
Abstract 2856: GLI3-mediated HH regulates prostate cancer progression
Authors: Thu Minh Duong, Marieke Oldenbroek Burleson, J J. Deng, T Qin, Das D, L-z Sun, T G. Boyer
Journal: Cancer Research (2021)

Abstract Although prostate cancer patients initially respond to androgen deprivation therapy, they eventually progress to lethal castration resistant prostate cancer (CRPC), characterized by restoration of the androgen receptor (AR) signaling despite castrate levels of circulating androgens. Mechanisms proposed to underlie CRPC include AR crosstalk with alternative signaling pathways. Among these, the Sonic hedgehog (SHH)Hedgehog (HH) pathway, an essential signaling axis in prostate development and homeostasis, has been implicated in prostate cancerCRPC progression. SHH pathway is regulated by transcription factors and effectors Glioma-associated oncogene family zinc finger (GLI) proteins 1, 2, and 3. Previous studies reported that GLI1 and GLI2 drive androgen-independent growth of prostate cancer by upregulating androgen-stimulated genes. However, whether and how GLI3 plays a role in prostate cancer progression remains unclear. In the present study, we investigated the role of GLI3 in the progression of prostate cancer cells. Like GLI2, GLI3 is the a downstream transcriptional factor effector of the SHH signaling pathway that can exist as a full-length activator form or a cleaved repressor form. Our data showed an increase in GLI3 expression in prostate cancer cells growing under androgen deprived conditions. Thuserefore, we hypothesize that androgen deprivation leads to activation of the SHH signaling pathway which consequently activates GLI3 to promote androgen-independent growth of prostate cancer cells. We showed that knockdown of GLI3 repressed while overexpression of GLI3 promoted androgen-independent growth of prostate cancer cells. GLI3 knockdown also resulted in regression of castration-resistant outgrowth of xenograft tumors in mice. Additionally, transcriptomic analysis of GLI3 knockdown cells revealed that the SHH signaling pathway and epithelial mesenchymal transition (EMT) genes are altered suggesting that GLI3 regulates androgen-independent growth of prostate cancer cells through canonical SHH signaling pathway and likely contributes to prostate cancer metastasis. Lastly, our data demonstrated a physical and functional relationship between GLI3 and AR suggesting a functional crosstalk between SHH signaling and AR signaling pathways in advanced prostate cancer. Citation Format: Thu Minh Duong, Marieke Oldenbroek Burleson, J J. Deng, T Qin, Das D, L-z Sun, T G. Boyer. GLI3-mediated HH regulates prostate cancer progression [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 2856.
Primary organic vs. primary psychogenic erectile dysfunction: A cross-sectional study on patient’s characteristics and sexual function from a tertiary referral centre
Authors: E. Pozzi, G. Fallara, L. Candela, A. Costa, L. Boeri, P. Capogrosso, N. Schifano, F. Belladelli, D. Cignoli, G. Colandrea, M. Raffo, J. Cornelius, A. Costantino, A. Mattei, F. Montorsi, A. Salonia
Journal: European Urology (2021)
Robot-assisted laparoscopic radical cystectomy with intracorporeal ileal conduit diversion versus open radical cystectomy with ileal conduit in an ERAS setup (BORARC): A double-blinded, randomised feasibility study
Authors: S.L. Maibom, M.A. Røder, E.K. Aasvang, M. Rohrsted, P.O. Thind, P. Bagi, T. Kistorp, A.M. Poulsen, L.N. Salling, H. Kehlet, K. Brasso, U.N. Joensen
Journal: European Urology (2021)
Abstract 252: Navigating networks of oncology biomarkers mined from the scientific literature: A new open research tool
Authors: Kim Wager, Dheepa Chari, Steffan Ho, Tomas J. Rees, Robert J. Schijvenaars
Journal: Cancer Research (2021)

Abstract Introduction: Oncology biomarkers have a pivotal role in diagnosis, prognosis, assessment of disease progression and the prediction of treatment efficacy. There are &amp;gt; 5000 known biomarkers; some are well characterised, while others are emerging as biomarkers of potential interest. Biomarker panels, incorporating combinations of biomarkers, are increasingly used to enhance the power and precision of testing. Objective: We sought to identify key emerging biomarkers and biomarker relationships by applying analytical techniques to the corpus of recent scientific publications using an artificial intelligence (AI)-driven platform. Methods: Biomarker targets were obtained from the Early Detection Research Network. Recent (&amp;lt;5 years old) publications mentioning biomarkers in six cancer types (bladder, breast, colorectal, lung, prostate and renal) were identified using Dimensions (a linked research knowledge system); emerging biomarkers were identified by number and growth in publications. For selected biomarkers, full text proximity searching was used to identify biomarker co-occurrence, which was visualized and characterized using network analysis and co-occurrence heatmaps per cancer type. Relationships between biomarkers were also assessed in an indication-agnostic dataset. Key biomarkers were identified by a measure of their network importance. Results: A total of 720 biomarkers were analyzed, and 41 clusters identified across the cancer types. Data visualizations are available at https://reports.dimensions.ai/mined-oncology-biomarkers/ Conclusion: Using large-scale analytics of published literature, biomarkers across six cancer types were successfully characterized in terms of their emergence in the published literature and the context in which they are described. This novel AI-driven approach could help identify biomarkers and biomarker panels for exploration in a clinical setting. Example clusters - growth rate is compound annual growth rate (CAGR)Cancer typeBiomarkers (n)Publications (n)Cluster key biomarkersCluster publication growth rate (%)Bladder49168CAV1/CXCL8/THBS153.1Breast2651593AREG/CXCL10/CXCL832.6Colorectal193921CAV1/CDCP1/MTHFR31.6Lung2231061SFTPC/C9/GPI41.4Prostate166717FABP5/FLNA/CAV131.6Renal44185CXCL10/CXCL8/CSNK2A149.5 Citation Format: Kim Wager, Dheepa Chari, Steffan Ho, Tomas J. Rees, Robert J. Schijvenaars. Navigating networks of oncology biomarkers mined from the scientific literature: A new open research tool [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 252.
Abstract 407: Belantamab Mafodotin detection by protein electrophoresis: Assessing interference for defining clinical response
Authors: Fiona J. McClure
Journal: Cancer Research (2021)

Abstract Multiple Myeloma (MM) is a life threatening incurable cancer of the bone marrow resulting in plasma cell expansion and over production of plasma proteins or ‘M' proteins. Belantamab Mafodotin (Belamaf) is an antibody drug conjugate (ADC) for the treatment of multiple myeloma. The antibody component is an afucosylated IgG1 directed against B-cell maturation antigen (a protein expressed on normal B lymphocytes and multiple myeloma cells) conjugated to the microtubule inhibitor monomethylauristatin F (MMAF).Current criteria for assessing clinical response include changes in serum or urine M-protein levels by serum protein electrophoresis and immunofixation electrophoresis (IFE). Therapeutic use of ADC's has the potential to interfere with M-protein assessment by electrophoresis thus confounding clinical trial results. We aimed to modify an existing electrophoresis (EPS) platform (SAS-1 plus) to identify Belamaf in both saline and patients sera using a specific Anti-mcMMAF antibody.Objectives:1)To determine if Belamaf can be detected by serum protein electrophoresis and/or immunofixation electrophoresis methods that are used to measure ‘M' protein in MM patients. 2)If Belamaf can be detected by this assay, then determine if the detectable levels could interfere with defining clinical outcomes such as complete response*.By modifying an existing platform and using an mcMMAF specific antibody we were able to detect Belamaf in patients sera with no ‘M' protein at concentrations down to 0.5g/L by IFE. In multiple myeloma patients whose total protein concentrations were in excess of 90g/L Belamaf could be detected at 1.5g/L. Belamaf in patients sera can only be identified by anti-mcMMAF as anti-IgG and anti-IgKappa will detected those proteins present in sera in both MM and healthy patients.Belamaf could not be detected below 0.5g/L either by EPS or IFE using Anti-mcMMAF. As therapeutic Cmax levels of Belamaf are expected to be 0.04g/L, it will not be identified by EPS or IFE using the SAS-1 plus system. Further refinement of the SAS-1 plus system may achieve greater sensitive down to 0.2g/L (0.2g/L was detected using anti- IgG) however increased sensitivity and optimisation is highly unlikely to detected therapeutic concentrations of Belamaf.* Complete Response: Patients with CR must show that no abnormal monoclonal proteins (also called M-proteins) are present in the blood serum or urine. Citation Format: Fiona J. McClure. Belantamab Mafodotin detection by protein electrophoresis: Assessing interference for defining clinical response [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 407.
Development and validation of a new nomogram for predicting surgical outcome in posterior retroperitoneoscopic adrenalectomy based on preoperative patient characteristics
Authors: A. Van Uitert, E.C.J. Van De Wiel, J. Ramjith, J. Deinum, H.J. Timmers, J.A. Witjes, L. Schulze Kool, J.F. Langenhuijsen
Journal: European Urology (2021)
Abstract 2068: Radiotherapy is associated with a deletion signature that contributes to poor cancer patient outcomes
Authors: Emre Kocakavuk, Kevin J. Anderson, Kevin C. Johnson, Frederick S. Varn, Samirkumar B. Amin, Erik P. Sulman, Floris P. Barthel, Roel G. Verhaak
Journal: Cancer Research (2021)

Abstract Diffuse gliomas are highly aggressive brain tumors that invariably relapse despite treatment with chemo- and radiotherapy. Treatment with alkylating chemotherapy can drive tumors to develop a hypermutator phenotype. In contrast, the genomic effects of radiation therapy (RT) remain unknown. We analyzed the mutational spectra following treatment with ionizing radiation in sequencing data from 190 paired primary-recurrent gliomas from the Glioma Longitudinal Analysis (GLASS) dataset and 2116 post-treatment metastatic tumors from the Hartwig Medical Foundation. We identified a significant increase in the burden of small deletions following radiation therapy that was independent of other factors and was significantly associated with the clinically applied RT-dosage in Gy (P = 1e-02, multivariable log-linear regression). These novel deletions demonstrated distinct characteristics when compared to pre-existing deletions present prior to RT-treatment and deletions in RT-untreated tumors. Radiation therapy-acquired deletions were characterized by a larger deletion size (GLASS and metastatic cohort, P = 1.2e-02 and P = 8e-11, respectively; Mann-Whitney U test), an increased distance to repetitive DNA elements (P &amp;lt; 2.2e-16, Kolmogorov-Smirnov test) and a reduction in microhomology at breakpoints (P = 3.2e-02, paired Wilcoxon signed-rank test). These observations suggested that canonical non-homologous end joining (c-NHEJ) was the preferred pathway for DNA double strand break repair of RT-induced DNA damage. Furthermore, radiotherapy resulted in frequent chromosomal deletions and significantly increased frequencies of CDKN2A homozygous deletions. Finally, a high burden of RT-associated deletions was associated with worse clinical outcomes (GLASS and metastatic cohort, P &amp;lt; 1e-04 and P = 2.6e-02, respectively; Wald test). Our results collectively suggest that effective repair of RT-induced DNA damage is detrimental to patient survival and that inhibiting c-NHEJ may be a viable strategy for improving the cancer-killing effect of radiotherapy. Taken together, the identified genomic scars as a result of radiation therapy reflect a more aggressive tumor with increased levels of resistance to follow up treatments. Citation Format: Emre Kocakavuk, Kevin J. Anderson, Kevin C. Johnson, Frederick S. Varn, Samirkumar B. Amin, Erik P. Sulman, Floris P. Barthel, Roel G. Verhaak. Radiotherapy is associated with a deletion signature that contributes to poor cancer patient outcomes [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 2068.
Abstract 155: A machine learning approach for accurate medulloblastoma subtyping using arm-level SCNAs
Authors: Cheng Yan, Dan Wang, Lan Su, Yufei Yang, Hao Du
Journal: Cancer Research (2021)

Abstract Background: In 2010, scientific community reached a consensus regarding its subtyping (WNT/β-catenin, Sonic Hedgehog, Group 3, and Group 4). Research demonstrated that different subtype displays distinct genotypic characteristics as well as prognostics. Currently, transcriptomic profiling via NanoString is well-accepted for medulloblastoma subtyping. However, this platform requires high quality RNA sample. An alternative approach is in need for more robust and accurate subtyping. In this study, we explored the feasibility of using machine learning approach for medulloblastoma subtyping based on genome-wide SCNVs. Method: We retrieved SNP array CEL data of 1097 medulloblastoma (GSE37385) from GEO. 800 samples were remained for further analysis after QC. 32 medulloblastoma samples were collected from Robinson G, et's study as independent validation set. Penncnv was used to calculate log R ratio and B allele frequency. DNAcopy was used for CNV segmentation. GISTIC2 was applied to obtain arm and focal SCNAs. A number of classifiers were trained using SCNAs as well as age and gender. Feature selection was conducted in a model specific manner. Model performance was assessed using AUROC. Result: Benchmark on validation set showed that accuracy of Naïve Bayes, Random Forest, AdaBoost, Logistic Regression and SVM are 76.25%, 75%, 75%, 77.5% and 80.62% respectively. AUROC is 90.98%, 92.3%, 91.32%, 92.1% and 92.02% in corresponding order. The relatively overfitting and comparable performance across most models implied that SCNAs own moderate predictive power in medulloblastoma subtyping. Generally, SVM with linear kernel demonstrated superior and balanced performance than other models. Feature importance evaluation via Random Forest and AdaBoost showed better predictive power of arm-level SCNAa of 6p, 6q, 7p, 7q, 16q, 17p, 17q, consistently with previous studies. Focal SCNAs on SIRPB1 and age owned high predictive power. Nanostring performs poorly on distinguishing Group 3 and Group 4. Our method showed same tendency, indicating transcriptomic as well as genomic similarity between these two groups. We decided to permit 10% of validation samples as ‘prediction failure' for those with highly similar SCNAs characteristics. Upon this modification, accuracy of most model raised 3% on average. Conclusion: Our study evaluated the feasibility of using genome-wide SCNAs profile for medulloblastoma subtyping. Benchmark showed moderate predictive power using SCNAs. Among a number of machine learning approaches, SVM with linear kernel demonstrated superior performance. Citation Format: Cheng Yan, Dan Wang, Lan Su, Yufei Yang, Hao Du. A machine learning approach for accurate medulloblastoma subtyping using arm-level SCNAs [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 155.
Deep learning system for automatic detection of bladder tumors in cystoscopic images
Authors: J. Mutaguchi, M. Oda, S. Ueda, F. Kinoshita, H. Naganuma, T. Matsumoto, K. Lee, K. Monji, K. Kashiwagi, A. Takeuchi, M. Shiota, J. Inokuchi, K. Mori, M. Eto
Journal: European Urology (2021)
Abstract 14085: Incident Congestive Heart Failure is Associated with Carotid Artery Inter-Adventitial Diameters in MESA (Multi-Ethnic Study of Atherosclerosis).
Authors: Joseph F Polak, Quenna Wong, W C Johnson, Wendy S Post, Anita Harrington, Daniel H O'Leary, N D Yanez
Journal: Circulation (2011)

Background: Carotid intima media thickness is associated with risk for CVD events. Relatively little is known about inter-adventitial diameter (IAD) of the common-carotid artery, a possible marker ...
Is a New Era Coming for Bronchopulmonary Dysplasia Prevention With Corticosteroids?—Reply
Authors: Nehal A. Parikh
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Management of local recurrence after radical nephrectomy: Surgical removal is still the gold standard. Results from a multicenter international cohort
Authors: M. Marchioni, P. Sountoulides, M. Furlan, M.C. Mir, L. Aretano, J. Rubio-Briones, M. Alvarez-Maestro, A.A. Bazan, A. Antonelli, C. Simeone, L. Schips
Journal: European Urology (2021)
Abstract 2422: Genetic aberrations of <i>Anaplastic Lymphoma Kinase (ALK)</i> are functional drivers in head and neck squamous cell carcinoma (HNSCC)
Authors: Lan Wang, Thomas Chun Kit Yeung, Hoi-Lam Ngan, Peony Hiu Yan Poon, Vivian Wai Yan Lui
Journal: Cancer Research (2021)

Abstract Head and neck squamous carcinoma (HNSCC) is a cancer with high genetic heterogeneity. Fusions of Anaplastic Lymphoma Kinase (ALK) have been widely described as a functional driver for lung cancer. Yet, mutations and amplification of ALK are found in HNSCC as well as many other human cancers. Their biological impacts on cancer cell growth are underexplored. Using the Cancer Genome Atlas (TCGA) HNSCC dataset (Firehose Legacy; N=510), we identified a subset of HNSCC patients harboring ALK aberrations (4%), including 0.4% cases with gene amplification and 3.5% with somatic mutations. Transcriptome analysis showed significant tumor-specific ALK upregulation in 43 adjacent normal-HNSCC tumor pairs (2-fold, p=0.001***, TCGA HNSCC Firehose Legacy). Interestingly, clinical analysis revealed that ~94% HNSCC patients with ALK amplification and mutations have advanced diseases (stage III or IV). Among the HNSCC-associated ALK aberrations, ALK amplification, as well as ALK p.R401L mutations are recurrent events. Thus, we sought to investigate their biological functions by ectopic expressions into an HNSCC cell line, FaDu, via retroviral infection. We found that overexpression of ALK WT gene (mimicking gene amplification) and ALK p.R401L significantly promoted cell proliferation vs. EGFP-control (p=0.0004***, 0.01*, respectively). Clonogenic assay also demonstrated both events to be drivers for colony survival vs. EGFP-control by 120%, 150% (p=0.02*, 0.0025**, respectively). Lastly, both events markedly increase FaDu cells invasiveness by Matrigel invasion assay by 67%, 58% (vs. EGFP-control, p&amp;lt;0.0001****, 0.0001****, respectively). In conclusion, ALK aberrations are functional drivers promoting HNSCC aggressiveness. Acknowledgements: This study is funded by General Research Fund, Research Grant Council, Hong Kong Government, Hong Kong SAR (#17121616 ). VWYL also receives funding supports from General Research Fund, Research Grant Council, Hong Kong Government, Hong Kong SAR (#17121616, #14168517), Research Impact Fund (#R4015-19F, R4017-18), the Health and Medical Research Fund (HMRF#15160691) from the Health and Medical Research Fund, the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region), University-Industry Collaboration Programme (UIM/329; Innovation and Technology Fund, Hong Kong Government, Hong Kong SAR), and the Hong Kong Cancer Fund, Hong Kong SAR. Citation Format: Lan Wang, Thomas Chun Kit Yeung, Hoi-Lam Ngan, Peony Hiu Yan Poon, Vivian Wai Yan Lui. Genetic aberrations of Anaplastic Lymphoma Kinase (ALK) are functional drivers in head and neck squamous cell carcinoma (HNSCC) [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 2422.