tbuckley/cabot-search huggingface dataset:
Abstract PS19-17: The role of myoglobin in breast cancer
Authors: Mostafa A. Aboouf, Julia Armbruster, Franco Guscetti, Markus Thiersch, Max Gassmann, Thomas A. Gorr
Journal: Cancer Research (2021)

Abstract Breast cancer today is typically seen as malignancy with longer survival due to early-detection diagnostics, yet the cancer remains by far the most common tumor type in adult females. Recently, our group co-discovered myoglobin (MB) to be expressed in luminal cells of healthy and cancerous breast epithelia of human and mice. In human patients, MB positivity emerged as hallmark of the luminal subtype and was directly correlated with estrogen receptor alpha positivity and hence a significantly better prognosis. Cancerous cells’ MB also appears to interact with the known tumor suppressor p53. However, if and how myoglobin itself restricts mammary tumorigenesis is completely unclear. To understand how MB exerts its alleged tumor-suppressive effects and if it impacts response of mammary tumors to chemo- and/or radiotherapy, we examine the molecular role of MB in breast tumor formation and progression through a) in vitro studies (MCF7 breast cancer BrCa cell clones; wildtype (wt) controls versus CRISPR/Cas9-engineered clones of a MB and/or p53 knockout (MBko/p53ko), b) in vivo mouse models to obtain spontaneously forming breast tumors, with or without MB, in a p53 deficient background. Comparing MCF7 BrCa MBko and p53ko clones vs. their corresponding wildtype counterpart supports our hypothesis of a feed forward loop between MB and p53 proteins, besides interfering with estrogen receptor expression. In addition to that, loss of MB was noticed to exert p53-independent upregulation on cell cyclins with more S phase cell population. That was reflected by a significant increase in survival of the MBko cells, in presence or absence of p53. Hypoxic MBko cells exhibited a partial epithelial to mesenchymal transition and hence a more migratory phenotype, relative to MBwt controls. Additionally, MB seems to stimulate apoptosis of the normoxic cancer cells. On the other hand, murine tumors were found to phenocopy human BrCa in the extent of their MB expression. Interestingly, MB-devoid tumors showed a significantly higher proliferation index and fat accumulation. Further studies will look into the clinical significance of that. In conclusion, MB seems to occupy unknown roles in cancer cells beyond or different from its classical O2 storage/transport functions. Unraveling these novel roles in governing tumor development and virulence will hopefully provide innovative strategies for future breast cancer interventions. Citation Format: Mostafa A. Aboouf, Julia Armbruster, Franco Guscetti, Markus Thiersch, Max Gassmann, Thomas A. Gorr. The role of myoglobin in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS19-17.
Incontinence is lonely and hard to talk about
Authors: Luce Brett
Journal: BMJ (2021)

Incontinence is lonely and hard to talk aboutLuce Brett shares what it is like to speak with a healthcare professional about incontinence Luce BrettI became incontinent at the age of 30, after the birth of my first baby, with urge and stress incontinence.Initially, both conditions responded well to bladder training and physiotherapy, but after the birth of my second child, the stress incontinence became increasingly problematic.Since then I have had many treatments, with varying success.
Vaccination against COVID-19: Expectations and concerns of patients with autoimmune and rheumatic diseases
Authors: Renaud Felten, Maxime Dubois, Manuel F Ugarte-Gil, Aurore Chaudier, Lou Kawka, Hugo Bergier, Charlotte Costecalde, Luc Pijnenburg, Jérémy Fort, Emmanuel Chatelus, Christelle Sordet, Rose-Marie Javier, Jacques-Eric Gottenberg, Jean Sibilia, Yurilis Fuentes-Silva, Laurent Arnaud
Journal: The Lancet Rheumatology (2021)
Multiphoton‐Guided Creation of Complex Organ‐Specific Microvasculature
Authors: Samuel G. Rayner, Caitlin C. Howard, Christian J. Mandrycky, Stefan Stamenkovic, Jonathan Himmelfarb, Andy Y. Shih, Ying Zheng
Journal: Advanced Healthcare Materials (2021)

Engineering functional human tissues in vitro is currently limited by difficulty replicating the small caliber, complex connectivity, cellularity, and 3D curvature of the native microvasculature. Multiphoton ablation has emerged as a promising technique for fabrication of microvascular structures with high resolution and full 3D control, but cellularization and perfusion of complex capillary-scale structures has remained challenging. Here, multiphoton ablation combined with guided endothelial cell growth from pre-formed microvessels is used to successfully create perfusable and cellularized organ-specific microvascular structures at anatomic scale within collagen hydrogels. Fabrication and perfusion of model 3D pulmonary and renal microvascular beds is demonstrated, as is replication and perfusion of a brain microvascular unit derived from in vivo data. Successful endothelialization and blood perfusion of a kidney-specific microvascular structure is achieved, using laser-guided angiogenesis. Finally, proof-of-concept hierarchical blood vessels and complex multicellular models are created, using multistep patterning with multiphoton ablation techniques. These successes open new doors for the creation of engineered tissues and organ-on-a-chip devices.
Total predicted MHC-I epitope load is inversely associated with population mortality from SARS-CoV-2
Authors: Eric A. Wilson, Gabrielle Hirneise, Abhishek Singharoy, Karen S. Anderson
Journal: Cell Reports Medicine (2021)

Polymorphisms in MHC-I protein sequences across human populations significantly affect viral peptide binding capacity, and thus alter T cell immunity to infection. In the present study, we assess the relationship between observed SARS-CoV-2 population mortality and the predicted viral binding capacities of 52 common MHC-I alleles. Potential SARS-CoV-2 MHC-I peptides are identified using a consensus MHC-I binding and presentation prediction algorithm called EnsembleMHC. Starting with nearly 3.5 million candidates, we resolve a few hundred highly probable MHC-I peptides. By weighing individual MHC allele-specific SARS-CoV-2 binding capacity with population frequency in 23 countries, we discover a strong inverse correlation between predicted population SARS-CoV-2 peptide binding capacity and mortality rate. Our computations reveal that peptides derived from the structural proteins of the virus produce a stronger association with observed mortality rate, highlighting the importance of S, N, M, and E proteins in driving productive immune responses.
Oral Rimegepant Safe, Effective for Migraine Prevention
Authors: Anita Slomski
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Dynamic monitoring of LLC lung metastasis development and prevention
Authors: Ling Geng, Katherine L. Osusky, Allie Fu, Dennis E. Hallahan
Journal: Cancer Research (2005)

4633  This study focuses on tumor cell survival and angiogenesis after tumor cell intravasation of vasculature. Dynamic monitoring was performed using the mouse lung metastasis model treated with platelet activation inhibitor (PGI2) and VEGFR inhibitor (SU5416). 3x105 DiI labeled LLC (Lewis lung carcinoma) cells were injected into the tail veins of C57BL6J mice to develop tumor metastasis in lung. The experimental animals were divided into control, PGI2 (100ug/mouse, once), and SU5416 (25mg/kg daily, for 5 days) groups. Lung, liver, and spleen frozen sections were cut and stained with DAPI at 15 min, 24 hours, 4 days, 8 days, 13 days and 15 days after injection of LLC cells for fluorescence microscopy assay. A similar experiment was performed (5 mice each group) and lung and liver were investigated at 15 days after injection of LLC cells for metastasis tumor colonies. A novel vivo and vitro combination technique was developed to test platelet active LLC cells binding on HUVEC capillary-like structures. The capability of VEGFR inhibitor (SU 5416) in blocking new vasculature development was tested in a mouse dorsal vascular window model. The dynamic monitoring shows that DiI labeled LLC cells accumulated in the lungs of all treatment groups (with slightly less accumulation in mice treated with PGI2). Very little DiI labeled LLC cells accumulated in liver and spleen at 15 min after injection. At the 24 hours and 4 days time points, DiI( red ) density was increasing in liver and spleen, but decreased at 8 day, 13 day, and 15 day time points. Meanwhile, DiI density in lung was changing with time, treatment, and tumor cell survival. Lung surface tumor colony counts show that there are 40-50 times more colonies in control lungs than SU5416 and combination groups, and the weights of lungs are also significantly different. Histology evidence is consistent with the above results. PGI2 significantly reduced LLC cell binding to HUVEC capillary-like structures (10 times lower). The dorsal window model with LLC cells showed that treatment with 5 doses of the VEGFR inhibitor SU5416 (3 mice) completely impeded angiogenesis compared to the control (3 mice). Conclusions: 1).The first several days are crucial in LLC cells developing metastasis in lung after intravasation. 2). VEGFR inhibitor (SU5416) can significantly prevent LLC cells from developing metastasis in lung. 3). Platelet activation inhibitor (PGI2) efficiently reduces LLC cell adhesion on endothelium (HUVEC). 4). VEGFR inhibitor (SU5416) is seemingly more effective than platelet activation inhibitor (PGI2) in impeding LLC lung metastasis formation after intravasation.
Neutrophil extracellular traps, disease severity, and antibiotic response in bronchiectasis: an international, observational, multicohort study
Authors: Holly R Keir, Amelia Shoemark, Alison J Dicker, Lidia Perea, Jennifer Pollock, Yan Hui Giam, Guillermo Suarez-Cuartin, Megan L Crichton, Mike Lonergan, Martina Oriano, Erin Cant, Gisli G Einarsson, Elizabeth Furrie, J Stuart Elborn, Christopher J Fong, Simon Finch, Geraint B Rogers, Francesco Blasi, Oriol Sibila, Stefano Aliberti, Jodie L Simpson, Jeffrey T J Huang, James D Chalmers
Journal: The Lancet Respiratory Medicine (2021)
Understanding molecular mechanisms of biologics drug delivery and stability from NMR spectroscopy
Authors: Pyae Phyo, Xi Zhao, Allen C. Templeton, Wei Xu, Jason K. Cheung, Yongchao Su
Journal: Advanced Drug Delivery Reviews (2021)

Protein therapeutics carry inherent limitations of membrane impermeability and structural instability, despite their predominant role in the modern pharmaceutical market. Effective formulations are needed to overcome physiological and physicochemical barriers, respectively, for improving bioavailability and stability. Knowledge of membrane affinity, cellular internalization, encapsulation, and release of drug-loaded carrier vehicles uncover the structural basis for designing and optimizing biopharmaceuticals with enhanced delivery efficiency and therapeutic efficacy. Understanding stabilizing and destabilizing interactions between protein drugs and formulation excipients provide fundamental mechanisms for ensuring the stability and quality of biological products. This article reviews the molecular studies of biologics using solution and solid-state NMR spectroscopy on structural attributes pivotal to drug delivery and stability. In-depth investigation of the structure-function relationship of drug delivery systems based on cell-penetrating peptides, lipid nanoparticles and polymeric colloidal, and biophysical and biochemical stability of peptide, protein, monoclonal antibody, and vaccine, as the integrative efforts on drug product design, will be elaborated.
Co‐occurrence of germline pathogenic variants for different hereditary cancer syndromes in patients with Lynch syndrome
Authors: Rosario Ferrer‐Avargues, María Isabel Castillejo, Estela Dámaso, Virginia Díez‐Obrero, Noemí Garrigos, Tatiana Molina, Alan Codoñer‐Alejos, Ángel Segura, Ana Beatriz Sánchez‐Heras, Adela Castillejo, José Luis Soto
Journal: Cancer Communications (2021)

Abstract Background Lynch syndrome (LS) is a hereditary condition characterized by a high risk of colorectal cancer, endometrial cancer, and other neoplasia associated with germline alterations in DNA mismatch repair genes. The classical genetic diagnostic strategy for LS consists of the Sanger sequencing of genes associated with the suspected syndrome. Next‐generation sequencing (NGS) enables the simultaneous sequencing of a large number of hereditary cancer genes. Here, we aimed to study whether other germline pathogenic variants of hereditary cancer genes are present in patients with LS. Methods A cohort of 84 probands with a previous genetic diagnosis of LS by Sanger sequencing was reanalyzed using NGS via a commercial panel of 94 hereditary cancer genes by hybrid capture. The American College of Medical Genetics and Genomics criteria were used to classify the clinical significance of the variants. The findings of NGS were confirmed by Sanger sequencing. When possible, genetic analyses of the new findings in the proband's relatives were also performed by Sanger sequencing. Results We identified five families (6%), out of 84, with at least two germline pathogenic variants conferring to high or moderate risk in different dominant cancer‐predisposing genes: [ MLH1‐BRCA2‐NBN ], [ MLH1‐BRCA1 ], [ MSH2‐ATM ], [ MSH6‐NF1 ], and [ MLH1‐FANCA ]. Interestingly, only one out of these five families exhibited a clinical phenotype associated with the new pathogenic variants. The family with three pathogenic variants of the [ MLH1‐BRCA2‐NBN ] genes showed a high aggregation of tumors associated with LS and breast and ovarian cancer syndrome. Conclusions Our results showed that the co‐occurrence of more than one pathogenic variant in cancer‐predisposing genes was remarkable among cases of LS. In most cases, no clinicial manifestations were associated with the secondary pathogenic variants. Further studies are needed to confirm these findings and elucidate their clinical impact. Reanalysis of LS families should be considered only in families with mixed clinical phenotypes.
Abstract 19216: Optical Magnetic Twist Cytometry to Study the Effects of Desmin Cytoskeleton Modifications in an in vitro Model of Cardiac Hypertrophy
Authors: Giulio Agnetti, Steven An, Victoria Halperin Kuhns, Gordon F Tomaselli, Jennifer E Van Eyk
Journal: Circulation (2012)

Background: Desmin is the major protein component of the intermediate filaments (IF) cytoskeleton in the cardiac myocyte. Desmin phosphorylation modulates IF lattice formation and correlates with disease in canine and human models of heart failure (HF). In order to investigate the contribution of desmin phosphorylation to cell biophysics as a potential mechanism of contractile dysfunction and HF we employed optical magnetic twist cytometry (OMTC) to measure the elastic and frictional properties of cultured neonatal rat ventricular myocytes (NRVMs), under both basal conditions and after hypertrophy was induced by endothelin-1 (ET). We also characterized desmin phosphorylation by tandem mass spectrometry (MS2) and identified glycogen synthase kinase 3 (GSK3) as a modulator of desmin phosphorylation. Methods and Results: Freshly isolated NRVMs were incubated with RGD-coated magnetic beads, which avidly bind to the integrin receptors, localized at focal adhesions. The beads integrate with the cytoskeleton and can be magnetized and twisted using magnetic fields to measure cell stiffness and friction. In NRVMs, ET treatment alone (10 nM, 48 hrs) induced a 23%±3.0SE (n≥230, p=0.008) increase in cell stiffness in the presence of the contraction uncoupler heptanol (2 mM). Depolymerization of the other cytoskeleton components (microfilaments and microtubules) with selective inhibitors (cytochalasin D and colchicine, respectively, both 10μ M, 5min) was also achieved. Finally, we confirmed desmin phosphorylation at Ser-27 in NRVMs by MS2 and identified a mediator of desmin phosphorylation by phos-tag gels combined with a GSK3-specific inhibitor (BIO, 2μ M). Conclusion: OMTC was employed for the first time, to our knowledge, in NRVMs inaugurating the application of a powerful biophysical tool to the investigation of a well established in vitro model for cardiac hypertrophy. Desmin cytoskeleton was also monitored and a new signaling pathway for its phosphorylation identified which was associated with increased cell stiffness.
Abstract PS14-24: Multi-center trial in the treatment of ductal carcinoma in situ of breast using intra-operative electronic brachytherapy technique, results
Authors: Alam M.Nisar Syed
Journal: Cancer Research (2021)

Abstract Purpose: To report on the technique of intra-operative electronic brachytherapy, local control, side effects and complications after a single fraction of 2000 cGy at the time of partial mastectomy. Material &amp; Methods: 1200 patients with early stage invasive ductal carcinoma and carcinoma in situ were enrolled in the Multi-Center Trial. 246 (20.5%) patients among these 1200 patients had carcinoma in situ and were treated by a single fraction of 2000 cGy dose by intra-operative irradiation to the lumpectomy cavity using Xoft system of electronic brachytherapy at the time of partial mastectomy. 80% of the patients were Caucasian, 7% African American, 7% Hispanic and 6% others. Estrogen receptor was positive in 211 patients, negative in 28 patients and unknown/not assessed in 7 patients. Progesterone receptor was positive in 190 patients, negative in 45 patients and unknown/not assessed in 11 patients. All patients were BRCA negative. 34 (14%) patients had low grade tumors, 109 (44%) intermediate grade tumors, and 103 (42%) high grade tumors. Seroma occurred in 9.8%, induration in 7.6%, and significant fibrosis in 3.5% of the patients. 2/246 (1%) developed ipsilateral recurrence and one patient developed a gastrointestinal cancer. 118 (48%) patients had characteristics of ASTRO criteria being suitable, 108 (44%) cautionary and 20 (8%) unsuitable. Conclusion: The relatively early 2.3 year results of a single fraction of 2000 cGy by IORT to the lumpectomy cavity at the time of partial mastectomy using Xoft Axxent electronic brachytherapy in the treatment of carcinoma in situ of the breast is safe and associated with low morbidity and local recurrence with good to excellent cosmesis in 80% of the patients. Citation Format: Alam M.Nisar Syed. Multi-center trial in the treatment of ductal carcinoma in situ of breast using intra-operative electronic brachytherapy technique, results [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-24.
The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging
Authors: Alexandra C. McQuattie-Pimentel, Ziyou Ren, Nikita Joshi, Satoshi Watanabe, Thomas Stoeger, Monica Chi, Ziyan Lu, Lango Sichizya, Raul Piseaux Aillon, Ching-I Chen, Saul Soberanes, Zhangying Chen, Paul A. Reyfman, James M. Walter, Kishore R. Anekalla, Jennifer M. Davis, Kathryn A. Helmin, Constance E. Runyan, Hiam Abdala-Valencia, Kiwon Nam, Angelo Y. Meliton, Deborah R. Winter, Richard I. Morimoto, Gökhan M. Mutlu, Ankit Bharat, Harris Perlman, Cara J. Gottardi, Karen M. Ridge, Navdeep S. Chandel, Jacob I. Sznajder, William E. Balch, Benjamin D. Singer, Alexander V. Misharin, G.R. Scott Budinger
Journal: Journal of Clinical Investigation (2021)

Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older patients. We performed an integrated analysis of single-cell RNA-Seq data that revealed homogenous age-related changes in the alveolar macrophage transcriptome in humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, and parabiosis, we found that the lung microenvironment drove an age-related resistance of alveolar macrophages to proliferation that persisted during influenza A viral infection. Ligand-receptor pair analysis localized these changes to the extracellular matrix, where hyaluronan was increased in aged animals and altered the proliferative response of bone marrow-derived macrophages to granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that strategies targeting the aging lung microenvironment will be necessary to restore alveolar macrophage function in aging.
A Randomized, Phase II Study Evaluating the Efficacy and Safety of Anakinra in the Treatment of Gout Flares
Authors: Kenneth G. Saag, Puja P. Khanna, Robert T. Keenan, Sven Ohlman, Lisa Osterling Koskinen, Erik Sparve, Ann‐Charlotte Åkerblad, Margareta Wikén, Alexander So, Michael H. Pillinger, Robert Terkeltaub
Journal: Arthritis & Rheumatology (2021)

Objective To evaluate the efficacy and safety of anakinra compared to triamcinolone in the treatment of gout flares. Methods Patients for whom nonsteroidal antiinflammatory drugs and colchicine were not suitable treatments were enrolled in this multicenter, randomized, double‐blind study with follow‐up for up to 2 years. The study was designed to assess superiority of anakinra (100 or 200 mg/day for 5 days) over triamcinolone (40 mg in a single injection) for the primary end point of changed patient‐assessed pain intensity in the most affected joint (scored on a visual analog scale of 0–100) from baseline to 24–72 hours. Secondary outcome measures included: safety, immunogenicity, and patient‐ and physician‐assessed global response. Results One hundred sixty‐five patients were randomized to receive anakinra (n = 110) or triamcinolone (n = 55). The median age was 55 years (range 25–83), 87% were men, the mean disease duration was 8.7 years, and the mean number of self‐reported flares during the prior year was 4.5. A total of 301 flares were treated (214 with anakinra; 87 with triamcinolone). Anakinra in both doses and triamcinolone provided clinically meaningful reduction in patient‐assessed pain intensity in the first and subsequent flares. For the first flare, the mean decline in pain intensity from baseline to 24–72 hours for total anakinra and triamcinolone was −41.2 and −39.4, respectively ( P = 0.688). Anakinra performed better than triamcinolone for most secondary end points. There were no unexpected safety findings. The presence of antidrug antibodies was not associated with adverse events or altered pain reduction. Conclusion Anakinra was not superior to triamcinolone for the primary end point, but had comparable efficacy in pain reduction and was favored for most secondary end points. Anakinra is an effective option for gout flares when conventional therapy is unsuitable.