tbuckley/cabot-search huggingface dataset:
Predicting acute ovarian failure in female survivors of childhood cancer: a cohort study in the Childhood Cancer Survivor Study (CCSS) and the St Jude Lifetime Cohort (SJLIFE)
Authors: Rebecca A Clark, Sogol Mostoufi-Moab, Yutaka Yasui, Ngoc Khanh Vu, Charles A Sklar, Tarek Motan, Russell J Brooke, Todd M Gibson, Kevin C Oeffinger, Rebecca M Howell, Susan A Smith, Zhe Lu, Leslie L Robison, Wassim Chemaitilly, Melissa M Hudson, Gregory T Armstrong, Paul C Nathan, Yan Yuan
Journal: The Lancet Oncology (2020)
Dissecting racial disparities in multiple myeloma
Authors: Catherine R. Marinac, Irene M. Ghobrial, Brenda M. Birmann, Jenny Soiffer, Timothy R. Rebbeck
Journal: Blood Cancer Journal (2020)

Abstract Multiple myeloma (MM) is a fatal plasma cell dyscrasia with a median overall survival of 5 to 10 years. MM progresses from the more common but often subclinical precursor states of monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma (SMM) to overt MM. There are large racial disparities in all stages of the disease. Compared with Whites, Blacks have an increased MGUS and MM risk and higher mortality rate, and have not experienced the same survival gains over time. The roots of this disparity are likely multifactorial in nature. Comparisons of Black and White MGUS and MM patients suggest that differences in risk factors, biology, and clinical characteristics exist by race or ancestry, which may explain some of the observed disparity in MM. However, poor accrual of Black MGUS and MM patients in clinical and epidemiological studies has limited our understanding of this disparity and hindered its elimination. Disparities in MM survival also exist but appear to stem from inferior treatment utilization and access rather than underlying pathogenesis. Innovative and multidisciplinary approaches are urgently needed to enhance our understanding of disparities that exist at each stage of the MM disease continuum and facilitate their elimination.
A Phase II Study of Nilotinib, a Novel Tyrosine Kinase Inhibitor Administered to Patients with Hypereosiniphilic Syndrome (HES).
Authors: Philipp le Coutre, Andreas Hochhaus, Dominik Heim, Teresa Rafferty, Aaron Weitzman, Ming Zheng, Gökben Baskaynak, Gregor Verhoef
Journal: Blood (2006)
Comparison of 68Ga-PSMA PET/CT and Contrast-Enhanced MRI on Residual Disease Assessment of Juvenile Nasal Angiofibroma
Authors: Alok Thakar, Pirabu Sakthivel, Arun Prashanth, Ashu Seith Bhalla, Suresh Chandra Sharma, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2020)

Abstract Prostate-specific membrane antigen (PSMA) is expressed in the endothelial cells of tumor-associated neovasculature of various nonprostatic benign and malignant neoplasms including juvenile nasopharyngeal angiofibroma (JNA). Positive uptake on PET/CT imaging with 68 Ga-labeled PSMA is noted in a patient with residual disease after initial surgery without any abnormal uptake in postoperative fibrosis, in contrast to contrast-enhanced MRI, which was confirmed by biopsy. 68 Ga-PSMA PET/CT may be a useful tool clinically for identifying early biochemical recurrences and in specifically differentiating recurrences from surgical site reparative tissue.
Bioinspired tumor-homing nanoplatform for co-delivery of paclitaxel and siRNA-E7 to HPV-related cervical malignancies for synergistic therapy
Authors: Cong Xu, Wan Liu, Yuan Hu, Weiping Li, Wen Di
Journal: Theranostics (2020)

Because of the complexity of cancer, a combination of chemotherapy and gene therapy is an emerging treatment modality.To realize the full potential of this strategy, a smart, highly biocompatible nanosystem that enables the precise co-delivery of small-molecule anticancer drugs and small interfering RNA (siRNA) is urgently needed.This study aimed to improve the therapeutic effect against cervical cancer by using cancer cell membrane-camouflaged nanoparticles for simultaneous delivery of paclitaxel (PTX) and siRNA targeting E7.Methods: By camouflaging HeLa cell membranes onto siRNA/PTX co-loaded (lactic-co-glycolic acid) (PLGA) nanoparticles, a biomimetic dual-drug delivery system (Si/PNPs@HeLa) was developed to simultaneously deliver PTX and siRNA targeting E7.After evaluating the physicochemical characteristics as well as their cell uptake and biodistribution behavior, studies on the RNA interference efficiency and antitumor ability of Si/PNPs@HeLa in vitro and in vivo were further carried out.Results: The Si/PNPs@HeLa was capable of delivering PTX and siRNA simultaneously to HeLa cells both in vitro and in vivo.Moreover, benefiting from the recognition and adhesion molecules on the surface of HeLa cells, Si/PNPs@HeLa exhibited an improved immune escape ability and an increased tumor region accumulation (3-fold higher than bare nanoparticles).As a result, an excellent synergistic anti-tumor effect was observed in the HeLa tumor-bearing mice, with tumor volume inhibiting rates of 83.6% and no side effects in major organs.The mechanistic studies confirmed that E7 knockdown sensitized HeLa cells to PTX chemotherapy, mainly by inhibiting PTX-induced AKT pathway activation.Conclusion: Si/PNPs@HeLa, by integrating immune escape and tumor-homing ability, can serve as an efficient dual-drug delivery system to achieve precise treatment of cervical cancer through chemo-gene combined therapy.
Dupilumab (Dupixent) for Asthma
Authors: Kathleen Barry, Dinah Gorelik
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Management of hepatitis B in the era of checkpoint inhibition
Authors: Janice Dutcher
Journal: Journal for ImmunoTherapy of Cancer (2020)

Hepatitis B virus (HBV) is a major global health concern, affecting more than 350 million people worldwide. Its management in the setting of cancer treatment can be problematic, particularly with the use of immunological treatment modalities, but also with chemotherapy. Immunological perturbations by chemo or immunotherapy have the potential to permit viral hepatitis reactivation and acute hepatic failure. HBV management algorithms have evolved, based on host tumor factors, viral serological factors, and the specific antitumor agents planned. As new agents enter the antitumor armamentarium, their impact on HBV infection needs to be defined. Zhang et al provide data on the utility of antiviral therapy in the management of HBV antigen positive patients receiving checkpoint inhibitors (CPIs) in preventing hepatitis reactivation, and offers guidance for such management in endemic areas, suggesting that prophylaxis is highly effective in preventing reactivation. This is pertinent to Western cancer therapy also, as a recent study has documented the silent existence of positive hepatitis antigenemia among newly diagnosed cancer patients. Whereas antigen and viral DNA screening is standard of care in Asia and Western Pacific oncology practice, evaluation for latent hepatitis may become a necessary part of management worldwide as CPIs continue to expand their role.
Abstract OI: Novel non-canonical functions of EZH2 in triple negative breast cancer
Authors: CG Kleer
Journal: Cancer Research (2020)

Abstract Patients with distant metastasis at the time of diagnosis have significantly worse prognosis. Triple negative breast carcinomas (TNBC) are heterogeneous tumors with propensity to metastasize and a guarded short term prognosis. The link between breast cancer and regulators of cell type identity was demonstrated in 2003, when enhancer of zeste homolog 2, EZH2, was reportedly overexpressed in approximately 55% of breast cancer tissue samples and was significantly associated with estrogen receptor negative status and worse disease free and overall survival. As the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2), the methyltransferase EZH2 deposits trimethyl marks on histone tails of lysine 27 of histone H3 (H3K27me3) to effect transcriptional repression. However, in a subset (~ 30%) TNBC high levels of EZH2 are associated with low H3K27me3, suggesting the intriguing possibility that in this group of tumors EZH2 may promote progression through other unknown mechanisms. Recent studies have shown that in TNBC EZH2 may indeed function independent of PRC2 and H3K27me3 activity. During breast cancer initiation, EZH2 enhances breast cancer stem cells and mammary tumor development through transcriptional activation of NOTCH1 and upregulation of its signaling pathway. More recent data show that EZH2 protein binds to p38 MAP kinase with resulting EZH2 phosphorylation at threonine 367 and accumulation in the cytoplasm of TNBC cells. In breast cancer tissue samples, cytoplasmic pEZH2 T367 is significantly associated with low H3K27me3 levels and a triple negative phenotype. Mechanistically, pEZH2 T367 protein binds to cytoplasmic regulators of cell migration and invasion, and is required for metastasis. These studies demonstrate a H3K27me3-independent mechanism of EZH2 function in TNBC progression. Future investigations will be required to test the therapeutic potential of inhibiting EZH2 non-canonical mechanisms alone or in combination with pharmacological targeting of EZH2 methyltransferase activity in TNBC. Citation Format: CG Kleer. Novel non-canonical functions of EZH2 in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OI.
Re: Marloes van der Leest, Bas Israël, Eric Bastiaan Cornel, et al. High Diagnostic Performance of Short Magnetic Resonance Imaging Protocols for Prostate Cancer Detection in Biopsy-naïve Men: The Next Step in Magnetic Resonance Imaging Accessibility. Eur Urol 2019;76:574–81
Authors: Arnaldo Stanzione, Massimo Imbriaco, Renato Cuocolo
Journal: European Urology (2019)
Multiple Myeloma DREAM Challenge reveals epigenetic regulator PHF19 as marker of aggressive disease
Authors: Mike J. Mason, Carolina Schinke, Christine L. P. Eng, Fadi Towfic, Fred Gruber, Andrew Dervan, Brian S. White, Aditya Pratapa, Yuanfang Guan, Hongjie Chen, Yi Cui, Bailiang Li, Thomas Yu, Elias Chaibub Neto, Konstantinos Mavrommatis, Maria Ortiz, Valeriy Lyzogubov, Kamlesh Bisht, Hongyue Y. Dai, Frank Schmitz, Erin Flynt, None Dan Rozelle, Samuel A. Danziger, Alexander Ratushny, William S. Dalton, Hartmut Goldschmidt, Herve Avet-Loiseau, Mehmet Samur, Boris Hayete, Pieter Sonneveld, Kenneth H. Shain, Nikhil Munshi, Daniel Auclair, Dirk Hose, Gareth Morgan, Matthew Trotter, Douglas Bassett, Jonathan Goke, Brian A. Walker, Anjan Thakurta, Justin Guinney
Journal: Leukemia (2020)

While the past decade has seen meaningful improvements in clinical outcomes for multiple myeloma patients, a subset of patients does not benefit from current therapeutics for unclear reasons. Many gene expression-based models of risk have been developed, but each model uses a different combination of genes and often involves assaying many genes making them difficult to implement. We organized the Multiple Myeloma DREAM Challenge, a crowdsourced effort to develop models of rapid progression in newly diagnosed myeloma patients and to benchmark these against previously published models. This effort lead to more robust predictors and found that incorporating specific demographic and clinical features improved gene expression-based models of high risk. Furthermore, post-challenge analysis identified a novel expression-based risk marker, PHF19, which has recently been found to have an important biological role in multiple myeloma. Lastly, we show that a simple four feature predictor composed of age, ISS, and expression of PHF19 and MMSET performs similarly to more complex models with many more gene expression features included.
Spatiotemporal mapping of erythroid, stromal, and osteogenic niche formation to support physiologic red cell production in a three-dimensional hollow fibre perfusion bioreactor (Conference Abstract)
Authors: Mark Allenby, Asma Tahlawi, Ruth Misener, Susana Brito Dos Santos, Athanasios Mantalaris, Nicki Panoskaltsis
Journal: Blood (2016)
Concurrent imaging of vascularization and metabolism in a mouse model of paraganglioma under anti-angiogenic treatment
Authors: Caterina Facchin, Mailyn Perez-Liva, Anikitos Garofalakis, Thomas Viel, Anais Certain, Daniel Balvay, Thulaciga Yoganathan, Justine Woszczyk, Kelly De Sousa, Joevin Sourdon, Jean Provost, Mickael Tanter, Charlotte Lussey-Lepoutre, Judith Favier, Bertrand Tavitian
Journal: Theranostics (2020)

Rationale: Deregulation of metabolism and induction of vascularization are major hallmarks of cancer. Using a new multimodal preclinical imaging instrument, we explored a sequence of events leading to sunitinib-induced resistance in a murine model of paraganglioma (PGL) invalidated for the expression of succinate dehydrogenase subunit B (Sdhb-/-). Methods: Two groups of Sdhb-/- tumors bearing mice were treated with sunitinib (6 weeks) or vehicle (3 weeks). Concurrent Positron Emission Tomography (PET) with 2' -deoxy-2'-[18F]fluoro-D-glucose (FDG), Computed Tomography (CT) and Ultrafast Ultrasound Imaging (UUI) imaging sessions were performed once a week and ex vivo samples were analyzed by western blots and histology. Results: PET-CT-UUI enabled to detect a rapid growth of Sdhb-/- tumors with increased glycolysis and vascular development. Sunitinib treatment prevented tumor growth, vessel development and reduced FDG uptake at week 1 and 2 (W1-2). Thereafter, imaging revealed tumor escape from sunitinib treatment: FDG uptake in tumors increased at W3, followed by tumor growth and vessel development at W4-5. Perfused vessels were preferentially distributed in the hypermetabolic regions of the tumors and the perfused volume increased during escape from sunitinib treatment. Finally, initial changes in total lesion glycolysis and maximum vessel length at W1 were predictive of resistance to sunitinib. Conclusion: These results demonstrate an adaptive resistance of Sdhb-/- tumors to six weeks of sunitinib treatment. Early metabolic changes and delayed vessel architecture changes were detectable and predictable in vivo early during anti-angiogenic treatment. Simultaneous metabolic, anatomical and functional imaging can monitor precisely the effects of anti-angiogenic treatment of tumors.
Abstract 14748: Intrinsic Frequencies of Carotid Pressure Waveforms Predict Cardiovascular Disease Events: The Framingham Heart Study
Authors: Leroy L Cooper, Jian Rong, Niema M Pahlevan, Derek G Rinderknecht, Emelia J Benjamin, Naomi M Hamburg, Vasan S Ramachandran, Martin G Larson, Morteza Gharib, Gary F Mitchell
Journal: Circulation (2019)

Introduction and Hypothesis: Intrinsic frequencies (IFs) derived from arterial waveforms, representing the dominant instantaneous frequency during systole and diastole, are associated with cardiova...
Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis
Authors: Charlotte Rose Hawkey Hedin, Gina Sado, Nelson Ndegwa, Ellina Lytvyak, Andrew Mason, Aldo Montano-Loza, Alessio Gerussi, Francesca Saffioti, Douglas Thorburn, Emma Nilsson, Geir Larsson, Bjørn A. Moum, Kim N. van Munster, Cyriel Y. Ponsioen, Cynthia Levy, Nicholas F. Nogueira, Christopher L. Bowlus, Neta Gotlieb, Oren Shibolet, Kate D. Lynch, Roger W. Chapman, Christian Rupp, Mette Vesterhus, Kristin K. Jørgensen, Fredrik Rorsman, Christoph Schramm, João Sabino, Severine Vermeire, Alessandra Zago, Nora Cazzagon, Hanns-Ulrich Marschall, Henriette Ytting, Karima Ben Belkacem, Olivier Chazouilleres, Sven Almer, Annika Bergquist
Journal: Clinical Gastroenterology and Hepatology (2020)
High miR-133a levels in the circulation anticipates presentation of clinical events in familial hypercholesterolaemia patients
Authors: Rafael Escate, Teresa Padró, Rosa Suades, Sandra Camino, Ovidio Muñiz, Jose Luis Diaz-Diaz, Alessandro Sionis, Pedro Mata, Lina Badimon
Journal: Cardiovascular Research (2020)

Abstract Aims Presentation of acute events in patients with atherosclerosis remains unpredictable even after controlling for classical risk factors. MicroRNAs (miRNAs) measured in liquid biopsies could be good candidate biomarkers to improve risk prediction. Here, we hypothesized that miRNAs could predict atherosclerotic plaque progression and clinical event presentation in familial hypercholesterolaemia (FH) patients. Methods and results Circulating miRNAs (plasma, exosomes, and microvesicles) were investigated by TaqMan Array and RT-qPCR assays. Patients with genetic diagnosis of FH and healthy relatives from the SAFEHEART cohort were included. A differential signature of 10 miRNA was obtained by comparing two extreme phenotypes consisting of FH patients suffering a cardiovascular event (CVE) within a 8-year follow-up period (FH-CVE, N = 42) and non-FH hypercholesterolaemic relatives from the same cohort, matched for age and treatment, without CVE during the same period (nFH-nCVE, N = 30). The validation studies included two independent groups of patients with FH background (discovery group, N = 89, validation group N = 196), developing a future CVE (FH-CVE) or not (FH-nCVE) within the same time period of follow-up. Of the 10 miRNAs initially selected, miR-133a was significantly higher in FH-CVE than in FH-nCVE patients. Receiver operating characteristic analysis confirmed miR-133a as the best microRNA for predicting CVE in FH patients (0.76 ± 0.054; P &amp;lt; 0.001). Furthermore, Kaplan–Meier and COX analysis showed that high plasma miR-133a levels associated to the higher risk of presenting a CVE within the next 8 years (hazard ratio 3.89, 95% confidence interval 1.88–8.07; P &amp;lt; 0.001). In silico analysis of curate biological interactions related miR-133a with target genes involved in regulation of the cell-membrane lipid-receptor LRP6 and inflammatory cytokines (CXCL8, IL6, and TNF). These predictions were experimentally proven in human macrophages and endothelial cells transfected with agomiR-133a. Conclusion Elevated levels of miR-133a in the circulation anticipate those FH patients that are going to present a clinical CVE within the next 2 years (average). Mechanistically, miR-133a is directly related with lipid- and inflammatory signalling in key cells for atherosclerosis progression.
Psychological, social and contextual factors across recovery stages following a sport-related knee injury: a scoping review
Authors: Linda K Truong, Amber D Mosewich, Christopher J Holt, Christina Y Le, Maxi Miciak, Jackie L Whittaker
Journal: British Journal of Sports Medicine (2020)

Objective To explore the role of psychological, social and contextual factors across the recovery stages (ie, acute, rehabilitation or return to sport (RTS)) following a traumatic time-loss sport-related knee injury. Material and methods This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews and Arksey and O’Malley framework. Six databases were searched using predetermined search terms. Included studies consisted of original data written in English that identified or described a psychological, social or contextual factor related to recovery after a traumatic time-loss sport-related knee injury. Two authors independently conducted title–abstract and full-text reviews. Study quality was assessed using the Mixed Methods Appraisal Tool. Thematic analysis was undertaken. Results Of 7289 records, 77 studies representing 5540 participants (37% women, 84% anterior cruciate ligament tears, aged 14–60 years) were included. Psychological factors were investigated across all studies, while social and contextual factors were assessed in 39% and 21% of included studies, respectively. A cross-cutting concept of individualisation was present across four psychological (barriers to progress, active coping, independence and recovery expectations), two social (social support and engagement in care) and two contextual (environmental influences and sport culture) themes. Athletes report multiple barriers to recovery and valued their autonomy, having an active role in their recovery and diverse social support. Conclusion Diverse psychological, social and contextual factors are present and influence all stages of recovery following a traumatic sport-related knee injury. A better understanding of these factors at the time of injury and throughout rehabilitation could assist with optimising injury management, promoting RTS, and long-term health-related quality-of-life.
ETV4 Is Necessary for Estrogen Signaling and Growth in Endometrial Cancer Cells
Authors: Adriana C. Rodriguez, Jeffery M. Vahrenkamp, Kristofer C. Berrett, Kathleen A. Clark, Katrin P. Guillen, Sandra D. Scherer, Chieh-Hsiang Yang, Bryan E. Welm, Margit M. Janát-Amsbury, Barbara J. Graves, Jason Gertz
Journal: Cancer Research (2020)

Abstract Estrogen signaling through estrogen receptor alpha (ER) plays a major role in endometrial cancer risk and progression, however, the molecular mechanisms underlying ER's regulatory role in endometrial cancer are poorly understood. In breast cancer cells, ER genomic binding is enabled by FOXA1 and GATA3, but the transcription factors that control ER genomic binding in endometrial cancer cells remain unknown. We previously identified ETV4 as a candidate factor controlling ER genomic binding in endometrial cancer cells, and here we explore the functional importance of ETV4. Homozygous deletion of ETV4, using CRISPR/Cas9, led to greatly reduced ER binding at the majority of loci normally bound by ER. Consistent with the dramatic loss of ER binding, the gene expression response to estradiol was dampened for most genes. ETV4 contributes to estrogen signaling in two distinct ways. ETV4 loss affects chromatin accessibility at some ER bound loci and impairs ER nuclear translocation. The diminished estrogen signaling upon ETV4 deletion led to decreased growth, particularly in 3D culture, where hollow organoids were formed and in vivo in the context of estrogen-dependent growth. These results show that ETV4 plays an important role in estrogen signaling in endometrial cancer cells. Significance: Estrogen receptor alpha (ER) is a key oncogene in endometrial cancer. This study uncovers ETV4 as an important factor in controlling the activity of ER and the growth of endometrial cancer cells.