tbuckley/cabot-search huggingface dataset:
exploring profilin as a target for suppressing the migration of breast cancer cells
Authors: Li Zou, Vaishnavi Panchapakesa, Partha Roy
Journal: Cancer Research (2006)

4315   Objective: Profilin (an actin-binding protein that also interacts with several proline-rich proteins involved in the signaling pathways leading to cytoskeletal organization) has been implied as a tumor suppressor protein based on it’s reduced expression in invasive breast cancer cells and ability to reduce tumorigenicity when overexpressed in these cells. However, a direct functional relevance of reduced expression of profilin in the pathogenesis of breast cancer has not been established. The aims of the present study were to explore whether 1) loss of profilin confers neoplastic characteristics to mammary epithelial cells, and 2) perturbations of profilin alter the migration of breast cancer cells. Methods: Suppression of profilin expression was achieved via RNAi-mediated gene silencing. Other perturbations included overexpression of either fully functional or dominant negative mutants of profilin that are selectively impaired in binding to different ligands. Results: Suppression of profilin conferred several characteristics that are hallmarks for neoplastic characteristics to human mammary epithelial cells (HMEC) including increased cell proliferation and chemotactic migration, decreased cell-cell and cell-matrix adhesions. Silencing profilin expression also increased the migration of MDA-MB-231 breast cancer cells. Overexpression of profilin stimulated assembly of actin stress fibers and focal adhesions, with concomitant inhibition in cell migration. expression of dominant negative mutants of profilin that are defective in binding to either actin or it’s proline-rich ligands also suppressed the migration of MDA-MB-231 cells, but to a lesser extent compared to the action of overexpressed profilin, thus suggesting that a fully functional profilin is required for it’s maximal inhibitory effect on breast cancer cell migration. Conclusion: Our results for the first time indicate that reduced profilin expression may be functionally linked to the pathogenesis of breast cancer and that perturbation of cellular profilin could be an effective strategy to limit migration of breast cancer cells.
Treatment of Iron Deficiency After Gastric Bypass—Reply
Authors: Sameer B. Murali
Journal: JAMA (2020)

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
Biological Toxicity can be a Surrogate Marker of Efficacy in Patients (PTS) Treated with MTOR Inhibitors (MTORI) for MRCC
Authors: M. Jebali, J. Fouque, G. Fargues, A. Jouinot, R.T. Elaidi, S. Oudard, J. Medioni
Journal: Annals of Oncology (2012)
China coronavirus: WHO declares international emergency as death toll exceeds 200
Authors: Elisabeth Mahase
Journal: BMJ (2020)

The World Health Organization has declared the current novel coronavirus (2019-nCoV) outbreak to be a public health emergency of international concern, as latest figures show that nearly 10 000 people have been infected and that over 200 have died.

WHO’s emergency committee reconvened on 30 January—a week after it first met—to reassess the situation. Tedros Adhanom Ghebreyesus, WHO director general, said that the declaration was “not because of what is happening in China but because of what is happening in other countries.”

He warned, “Our greatest concern is for the virus to spread to countries with weaker health systems that are ill prepared to deal with it.”

The announcement was soon followed by the first two confirmed cases of the virus …
Enhanced Lipid Accumulation and Metabolism Are Required for the Differentiation and Activation of Tumor-Associated Macrophages
Authors: Pan Su, Qiang Wang, Enguang Bi, Xingzhe Ma, Lintao Liu, Maojie Yang, Jianfei Qian, Qing Yi
Journal: Cancer Research (2020)

Abstract Tumor-associated macrophages (TAM) are important tumor-promoting cells. However, the mechanisms underlying how the tumor and its microenvironment reprogram these cells remain elusive. Here we report that lipids play a crucial role in generating TAMs in the tumor microenvironment (TME). Macrophages from both human and murine tumor tissues were enriched with lipids due to increased lipid uptake by macrophages. TAMs expressed elevated levels of the scavenger receptor CD36, accumulated lipids, and used fatty acid oxidation (FAO) instead of glycolysis for energy. High levels of FAO promoted mitochondrial oxidative phosphorylation, production of reactive oxygen species, phosphorylation of JAK1, and dephosphorylation of SHP1, leading to STAT6 activation and transcription of genes that regulate TAM generation and function. These processes were critical for TAM polarization and activity, both in vitro and in vivo. In summary, we highlight the importance of lipid metabolism in the differentiation and function of protumor TAMs in the TME. Significance: This study highlights the role of lipid metabolism in the differentiation and function of TAMs and suggests targeting TAM fatty acid oxidation as a potential therapeutic modality for human cancers.
David Oliver: Conveyor belt medicine
Authors: David Oliver
Journal: BMJ (2020)

Over the New Year period I worked three 12 hour stints on the acute medical unit. What I saw, heard, and felt over those days, and over many others this winter, was nothing unusual for colleagues in acute care throughout the NHS. What it perhaps resembled most was an out-of-control conveyor belt, of the kind used to tragicomic effect by Charlie Chaplin in the 1936 film Modern Times .1 This one wasn’t carrying parts needing screws, however, but sick, frightened, or confused patients and their worried relatives. The operatives in this case weren’t depression era factory workers but clinical staff, struggling to deal with the relentless procession and unable to stop it.

We know that each clinical encounter really matters to patients and their relatives. It will be …
Estimation of Medicare Part D Spending on Insulin for Patients With Diabetes Using Negotiated Prices and a Defined Formulary
Authors: William B. Feldman, Benjamin N. Rome, Lisa Soleymani Lehmann, Aaron S. Kesselheim
Journal: JAMA Internal Medicine (2020)

This economic evaluation estimates insulin savings that would result if Medicare Part D used US Department of Veterans Affairs–negotiated prices and the Veterans Affairs formulary for patients with diabetes.
No place like home: initiation of non-invasive ventilation for stable severe COPD
Authors: Nicholas S Hill
Journal: Thorax (2020)

For nearly 60 years, clinicians and investigators have explored the possibility that non-invasive ventilatory assistance might improve the function of patients with stable severe chronic obstructive pulmonary disease (COPD).1 Early studies used negative pressure ventilators with the idea that the rest of the respiratory muscles would make them stronger, but these were poorly tolerated.2 For the past 30 years, studies using non-invasive positive pressure ventilation (NIV) have been performed to see if gas exchange and sleep quantity and quality would improve but results have been conflicting. As recently as 2013, a Cochrane analysis concluded that NIV for stable severe hypercapnic COPD ‘had no clinically or statistically significant effect on gas exchange, exercise tolerance, quality of life, lung function, respiratory muscle strength or sleep efficiency’ and should only be used in the context of a clinical trial’.3 

Over the past 5 years, though, several important studies have been published that have altered thinking about the role of NIV for stable severe COPD. Kohnlein et al 4 randomised almost 200 severe stable patients (PaCO2 >6.67 kPa) to receive ‘high-intensity’ NIV (inspiratory pressure to lower PaCO2 by at least 20% and backup rate 2 breaths/min below spontaneous), or standard home oxygen. Twelve-month mortality (12% vs 33%) and St George’s Respiratory Questionnaire score were significantly better in the NIV group. More recently, Murphy et al 5 using ‘high-pressure NIV’ (with a lower set respiratory rate to allow spontaneous triggering) showed significant prolongation of the time to rehospitalisation or death in the NIV group compared with the standard oxygen group (4.3 vs 1.4 months) in patients with hypercapnic COPD recovering from acute exacerbations. However, another randomised controlled trial examining the role of …
Comparing large pore lightweight mesh versus small pore heavyweight mesh in open mesh plug repair of primary and recurrent unilateral inguinal hernia – A questionnaire study for a retrospective analysis of a cohort of elective groin hernia patients using propensity score matching
Authors: Michael Krauß, Monika Heinzel-Gutenbrunner, Lutz Krönung, Ernst Hanisch, Alexander Buia
Journal: International Journal of Surgery (2020)
Dutch hospital resumes production of rare drug after sourcing purer ingredients
Authors: Tony Sheldon
Journal: BMJ (2020)

A university hospital in the Netherlands has resumed cost price production of orphan medicine chenodeoxycholic acid (CDCA), a primary bile acid used to treat the rare hereditary metabolic disorder cerebrotendinous xanthomatosis (CTX).

The pharmaceutical compounding initiative at Amsterdam University Medical Centre, which was intended to ensure access to the drug, was launched in 2018 after manufacturers, Leadiant Biosciences, increased the price of its CDCA fivefold.1

But production was suspended after a Dutch Health Care Inspectorate investigation found that the CDCA that the hospital made contained trace amounts of impurities.2 This month supply resumed following a year long …
Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation
Authors: Stuart A. Cook, Sebastian Schafer
Journal: Annual Review of Medicine (2020)

Interleukin (IL)-11 is upregulated in a wide variety of fibro-inflammatory diseases such as systemic sclerosis, rheumatoid arthritis, pulmonary fibrosis, inflammatory bowel disease, kidney disease, drug-induced liver injury, and nonalcoholic steatohepatitis. IL-11 is a member of the IL-6 cytokine family and has several distinct properties that define its unique and nonredundant roles in disease. The IL-11 receptor is highly expressed on stromal, epithelial and polarized cells, where noncanonical IL-11 signaling drives the three pathologies common to all fibro-inflammatory diseases—myofibroblast activation, parenchymal cell dysfunction, and inflammation—while also inhibiting tissue regeneration. This cytokine has been little studied, and publications on IL-11 peaked in the early 1990s, when it was largely misunderstood. Here we describe recent advances in our understanding of IL-11 biology, outline how misconceptions as to its function came about, and highlight the large potential of therapies targeting IL-11 signaling for treating human disease.
Preclinical efficacy of the GPER-selective agonist G-1 in mouse models of obesity and diabetes
Authors: Geetanjali Sharma, Chelin Hu, Daniela I. Staquicini, Jonathan L. Brigman, Meilian Liu, Franck Mauvais-Jarvis, Renata Pasqualini, Wadih Arap, Jeffrey B. Arterburn, Helen J. Hathaway, Eric R. Prossnitz
Journal: Science Translational Medicine (2020)

Human obesity has become a global health epidemic, with few safe and effective pharmacological therapies currently available. The systemic loss of ovarian estradiol (E2) in women after menopause greatly increases the risk of obesity and metabolic dysfunction, revealing the critical role of E2 in this setting. The salutary effects of E2 are traditionally attributed to the classical estrogen receptors ERα and ERβ, with the contribution of the G protein-coupled estrogen receptor (GPER) still largely unknown. Here, we used ovariectomy- and diet-induced obesity (DIO) mouse models to evaluate the preclinical activity of GPER-selective small-molecule agonist G-1 (also called Tespria) against obesity and metabolic dysfunction. G-1 treatment of ovariectomized female mice (a model of postmenopausal obesity) reduced body weight and improved glucose homeostasis without changes in food intake, fuel source usage, or locomotor activity. G-1-treated female mice also exhibited increased energy expenditure, lower body fat content, and reduced fasting cholesterol, glucose, insulin, and inflammatory markers but did not display feminizing effects on the uterus (imbibition) or beneficial effects on bone health. G-1 treatment of DIO male mice did not elicit weight loss but prevented further weight gain and improved glucose tolerance, indicating that G-1 improved glucose homeostasis independently of its antiobesity effects. However, in ovariectomized DIO female mice, G-1 continued to elicit weight loss, reflecting possible sex differences in the mechanisms of G-1 action. In conclusion, this work demonstrates that GPER-selective agonism is a viable therapeutic approach against obesity, diabetes, and associated metabolic abnormalities in multiple preclinical male and female models.
Ultrasound-mediated delivery of miRNA-122 and anti-miRNA-21 therapeutically immunomodulates murine hepatocellular carcinoma in vivo
Authors: Jennifer C. Wischhusen, Sayan Mullick Chowdhury, Taehwa Lee, Huaijun Wang, Sunitha Bachawal, Rammohan Devulapally, Rayhaneh Afjei, Uday Kumar Sukumar, Ramasamy Paulmurugan
Journal: Journal of Controlled Release (2020)
Rescuing Research Participants After Alzheimer Trials Stop Early
Authors: Emily A. Largent, Jason Karlawish
Journal: JAMA Neurology (2020)

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 Neurology 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 Neurology journal
Predicted Prognosis of Patients with Pancreatic Cancer by Machine Learning
Authors: Seiya Yokoyama, Taiji Hamada, Michiyo Higashi, Kei Matsuo, Kosei Maemura, Hiroshi Kurahara, Michiko Horinouchi, Tsubasa Hiraki, Tomoyuki Sugimoto, Toshiaki Akahane, Suguru Yonezawa, Marko Kornmann, Surinder K. Batra, Michael A. Hollingsworth, Akihide Tanimoto
Journal: Clinical Cancer Research (2020)

Pancreatic cancer remains a disease of high mortality despite advanced diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic cancers. MUC1 and MUC4 expression are related to the aggressive behavior of human neoplasms and a poor patient outcome. In contrast, MUC2 is a tumor suppressor, and we have previously reported that MUC2 is a favorable prognostic factor in pancreatic neoplasia. This study investigates whether the methylation status of three mucin genes from postoperative tissue specimens from patients with pancreatic neoplasms could serve as a predictive biomarker for outcome after surgery.We evaluated the methylation status of MUC1, MUC2, and MUC4 promoter regions in pancreatic tissue samples from 191 patients with various pancreatic lesions using methylation-specific electrophoresis. Then, integrating these results and clinicopathologic features, we used support vector machine-, neural network-, and multinomial-based methods to develop a prognostic classifier.Significant differences were identified between the positive- and negative-prediction classifiers of patients in 5-year overall survival (OS) in the cross-validation test. Multivariate analysis revealed that these prognostic classifiers were independent prognostic factors analyzed by not only neoplastic tissues but also nonneoplastic tissues. These classifiers had higher predictive accuracy for OS than tumor size, lymph node metastasis, distant metastasis, and age and can complement the prognostic value of the TNM staging system.Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with pancreatic ductal adenocarcinoma.
PREGNANCY DIAGNOSIS STATION: REPORT ON THIRD YEAR'S WORKING
Authors: B. P. Wiesner
Journal: BMJ (1932)

The second report' on the working of the Pregnancy Diagnosis Station, which was, like the first,2 published in this Journal, dealt with the cases diagnosed up to the end of January, 1931.The present report embodies the cases dealt with up to the end of January, 1932.As in previous reports, only cases submitted by practitioners, hospitals, or public health authorities are considered.
In vivo crosslinking strategies to identify and characterize transcription factor protein complexes
Authors: Ryan Bomgarden, Chris Etienne, Marty Wilkes, Barbara Kaboord, Peter Bell
Journal: Cancer Research (2007)

1192  Identification of protein-protein interactions is key to understanding the dynamic organization of cellular signaling networks. Traditionally, these transient interactions are studied using the general crosslinking reagent formaldehyde to stabilize protein-protein interactions prior to immunoprecipitation or visualization by immunofluorescent microscopy. However, formaldehyde crosslinks can be highly variable due to reagent polymerization and are also not protein-specific as they can immobilize proteins to DNA and other biological macromolecules. Here, we compare formaldehyde to other crosslinking reagents for studying protein-protein interactions in living cells. Using NHS-ester, amine-reactive homobifunctional crosslinkers DSG (disuccinimidyl glutarate), DSS (disuccinimidyl suberate) and DSP (dithio-bis-succinimidyl propionate), we were able to capture protein-specific interactions among protein subunits of transcription factor complexes. Alternatively, using a novel class of photo-reactive amino acids, Photo-methionine (L-2-amino-5,5’azi-hexanoic acid) and Photo-leucine (L-2-amino-4,4’azi-pentanoic acid), we have crosslinked transcription factor protein complexes directly within protein interaction interfaces. In addition, homobifunctional NHS-esters crosslinkers and photo-reactive amino acids were able to capture interactions among transcription factor proteins that could not be detected using formaldehyde alone. Both of these techniques provide unique advantages for studying transcription factor complexes and can be used to identify more diverse protein-protein interactions in living cells than those observed with formaldehyde.
ARID1A Hypermethylation Disrupts Transcriptional Homeostasis to Promote Squamous Cell Carcinoma Progression
Authors: Qingyu Luo, Xiaowei Wu, Wan Chang, Pengfei Zhao, Xiaolin Zhu, Hongyan Chen, Yabing Nan, Aiping Luo, Xuantong Zhou, Dan Su, Wenjie Jiao, Zhihua Liu
Journal: Cancer Research (2020)

Abstract Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complexes have a mutation rate of approximately 20% in human cancer, and ARID1A is the most frequently mutated component. However, some components of SWI/SNF complexes, including ARID1A, exhibit a very low mutation rate in squamous cell carcinoma (SCC), and their role in SCC remains unknown. Here, we demonstrate that the low expression of ARID1A in SCC is the result of promoter hypermethylation. Low levels of ARID1A were associated with a poor prognosis. ARID1A maintained transcriptional homeostasis through both direct and indirect chromatin-remodeling mechanisms. Depletion of ARID1A activated an oncogenic transcriptome that drove SCC progression. The anti-inflammatory natural product parthenolide was synthetically lethal to ARID1A-depleted SCC cells due to its inhibition of both HDAC1 and oncogenic signaling. These findings support the clinical application of parthenolide to treat patients with SCC with low ARID1A expression. Significance: This study reveals novel inactivation mechanisms and tumor-suppressive roles of ARID1A in SCC and proposes parthenolide as an effective treatment for patients with SCC with low ARID1A expression.
Acute cellular and vascular responses to photodynamic therapy using EGFR-targeted nanobody-photosensitizer conjugates studied with intravital optical imaging and magnetic resonance imaging
Authors: Henriette S. de Bruijn, Vida Mashayekhi, Tom J.L. Schreurs, Pieter B.A.A. van Driel, Gustav J. Strijkers, Paul J. van Diest, Clemens W.G.M. Lowik, Ann L.B. Seynhaeve, Timo L.M. ten Hagen, Jeanine J. Prompers, Paul M.P. van Bergen en Henegouwen, Dominic J. Robinson, Sabrina Oliveira
Journal: Theranostics (2020)

Targeted photodynamic therapy (PDT) has the potential to selectively damage tumor tissue and to increase tumor vessel permeability.Here we characterize the tissue biodistribution of two EGFR-targeted nanobody-photosensitizer conjugates (NB-PS), the monovalent 7D12-PS and the biparatopic 7D12-9G8-PS.In addition, we report on the local and acute phototoxic effects triggered by illumination of these NB-PS which have previously shown to lead to extensive tumor damage.Methods: Intravital microscopy and the skin-fold chamber model, containing OSC-19-luc2-cGFP tumors, were used to investigate: a) the fluorescence kinetics and distribution, b) the vascular response and c) the induction of necrosis after illumination at 1 or 24 h post administration of 7D12-PS and 7D12-9G8-PS.In addition, dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) of a solid tumor model was used to investigate the microvascular status 2 h after 7D12-PS mediated PDT.Results: Image analysis showed significant tumor colocalization for both NB-PS which was higher for 7D12-9G8-PS.Intravital imaging showed clear tumor cell membrane localization 1 and 2 h after administration of 7D12-9G8-PS, and fluorescence in or close to endothelial cells in normal tissue for both NB-PS.PDT lead to vasoconstriction and leakage of tumor and normal tissue vessels in the skin-fold chamber model.DCE-MRI confirmed the reduction of tumor perfusion after 7D12-PS mediated PDT.PDT induced extensive tumor necrosis and moderate normal tissue damage, which was similar for both NB-PS conjugates.This was significantly reduced when illumination was performed at 24 h compared to 1 h after administration.Discussion: Although differences were observed in distribution of the two NB-PS conjugates, both led to similar necrosis.Clearly, the response to PDT using NB-PS conjugates is the result of a complex mixture of tumor cell responses and vascular effects, which is likely to be necessary for a maximally effective treatment.