tbuckley/cabot-search huggingface dataset:
Abstract 2446: IL4 receptor-induced proliferation is mediated via Glut1 activity in metastatic breast cancer
Authors: Ebony Hargrove-Wiley, Daniel Valent, Demond Williams, Wendy Bindeman, Barbara Fingleton
Journal: Cancer Research (2021)

Abstract Breast cancer is the leading cause of cancer mortality in women. The breast cancer microenvironment supplies immune signals that influence tumor growth and metastatic behavior. The cytokine, Interleukin-4 (IL4), promotes increased survival, proliferation and invasion upon stimulation of the type II IL4 receptor alpha (IL4Rα) which is aberrantly expressed on epithelial cancer cells. Previously, we have shown that metastatic mouse mammary cancer cells have a strong dependence on IL4 signaling for colonization of metastatic sites in the lung and liver. Additionally, these cells uptake more glucose when treated with IL4 in vitro. Here, we assessed the importance of glucose consumption on pro-tumorigenic phenotypes induced by IL4/IL4Rα. In 4T1 cells, IL4/IL4Rα signaling increased protein expression of the glucose transporter, Glut1. IL4/IL4Rα activation also increased global glycosylation of Glut1. In human metastatic breast cancer cells (MDA-MB-231 and BT549), Crispr-mediated knockout (KO) of Glut1 significantly reduced glucose consumption when assayed by 2-NBDG uptake, a fluorescently labelled glucose analog. Additionally, Glut1 KO reversed the proliferative effects of IL4/IL4Rα stimulation on human cancer cells in vitro. Our data suggest that IL4-induced Glut1 expression supports the increased metabolic activity necessary for cancer cell proliferation. Targeting the IL4/IL4Rα signaling axis could potentially be a therapeutic strategy to impede tumor-associated metabolism and reduce tumor burden at primary and metastatic sites. Citation Format: Ebony Hargrove-Wiley, Daniel Valent, Demond Williams, Wendy Bindeman, Barbara Fingleton. IL4 receptor-induced proliferation is mediated via Glut1 activity in metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2446.
Abstract 2712: Donor selection strategies to optimize humanized mouse models for the evaluation of T cell engagers
Authors: Liqing Cheng, Jane Chen, Qunyan Yu, Natalia Malkova, Virna F. Cortez-Retamozo, Fangxian Sun, Sukhvinder Sidhu
Journal: Cancer Research (2021)

Abstract The success of early cancer immunotherapies has led to the development of novel therapeutic approaches including multi-specific antibodies engaging innate and adaptive effector cells. To evaluate the antitumor potency of these multi-specific cell engagers, we have established a protocol to select human PBMCs from donors of a commercial frozen source by their potency to produce inflammatory cytokines and the capacity to engraft into NOD-Scid IL2Rgammanull (NSG)mice. The selected human PBMCs were used to reconstitute NSG mice, or as donors of effector cells that upon in vitro expansion were adoptively transferred to NSG mice for humanization. We have employed these humanization strategies to evaluate T cell engagers, which are typically multi-specific antibodies directed against the T cell and one or multiple tumor-associated antigen (TAA), whose therapeutic strategy is to 1) engage T cells, 2) activate the T cells and 3) engage tumor cells, and thus induce tumor cell killing. We will present representative data from several humanization approaches using liquid and solid orthotopic tumor models to assess the effectiveness of multi-specific T cell engagers in mediating antitumor responses. Thus, pre-clinical evaluations rely on the development of optimized tumor bearing humanized models that mirror key properties of a human setting, to assess the therapeutic potential of anti-tumor multi-specific biologics. Citation Format: Liqing Cheng, Jane Chen, Qunyan Yu, Natalia Malkova, Virna F. Cortez-Retamozo, Fangxian Sun, Sukhvinder Sidhu. Donor selection strategies to optimize humanized mouse models for the evaluation of T cell engagers [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 2712.
FDA, FTC Warn Companies Claiming Their Supplements Treat Infertility
Authors: Bridget M. Kuehn
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
The utilization of intraoperative ultrasound in overcoming adherent perinephric fat In laparoscopic partial nephrectomy
Authors: M. Gulsen, E. Özden, İ. Çamlıdağ, S. Öner, Y. Bostancı, Y.K. Yakupoğlu, A.F. Yılmaz, Ş. Sarıkaya
Journal: European Urology (2021)
Abstract 5270: Crystal Structure of Nkx2.5 Homeodomain in Complex with Anf-242 Motif
Authors: Hyun-Joo Nam, Caroli Genis, Peyton Scone, Hideko Kasahara
Journal: Circulation (2008)

NKX2.5 is a homeodomain (HD) containing transcription factor preferentially expressed in cardiomyocytes. Mutations in the NKX2.5 gene have been identified in patients with congenital heart disease, suggesting its critical roles in cardiac development and maturation. NKX2.5 is reported to regulate transcription of atrial natriuretic factor (ANF), potentially through direct binding to -242 bp proximal promoter region (ANF-242). ANF-242 contains two palidromic NKX2.5 binding sites, and occupation of both sites by NKX2.5 has been reported. In addition, physical interaction between NKX2.5 proteins has been suggested to facilitate DNA binding through domains outside of the HD. However, detailed crystal structure of NKX2.5 protein is currently not available. The HD of human NKX2.5 (aa 138–197; C193S) with the oxidizable Cys193 substituted with Ser was co-crystallized with 19bp double stranded DNA including ANF-242 region. This mutant was reported to have the same DNA binding characteristics as the wild type. The crystal structure was determined at 1.8 Å resolution with final R-working and R-free values of 0.234 and 0.278, respectively. Consistent with previous studies, two molecules of NKX2.5 HD are bound to ANF-242 region without physical interaction between the two proteins. Column purification demonstrated that NKX2.5 behaves as dimers in solution in a concentration dependent manner. These results suggest that dimeric NKX2.5 HD in solution may change conformation upon DNA binding. Among various NK class proteins, the three-dimensional structure has only been determined in the HD of Drosophila vnd/NK2 (ventral nervous system defective proteins) using NMR. When the two HDs are compared, NKX2.5 HD shows extended DNA contacts to a total of 8 base pairs. Most of the residues of HD implicated in pathology of mutants are involved in DNA binding and structural stabilization. The structure of NKX2.5 HD with ANF-242 shows that the HD occupies two binding sites of ANF-242 without physical interaction between themselves. This high resolution crystal structure of NKX2.5 protein provides a detailed picture of protein and DNA interactions, which allows us to predict DNA binding of mutants identified in human patients. This research has received full or partial funding support from the American Heart Association, AHA Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico &amp; Tennessee).
Integration of personalized drug delivery systems into digital health
Authors: Dhara Raijada, Katarzyna Wac, Emanuel Greisen, Jukka Rantanen, Natalja Genina
Journal: Advanced Drug Delivery Reviews (2021)

Personalized drug delivery systems (PDDS), implying the patient-tailored dose, dosage form, frequency of administration and drug release kinetics, and digital health platforms for diagnosis and treatment monitoring, patient adherence, and traceability of drug products, are emerging scientific areas. Both fields are advancing at a fast pace. However, despite the strong complementary nature of these disciplines, there are only a few successful examples of merging these areas. Therefore, it is important and timely to combine PDDS with an increasing number of high-end digital health solutions to create an interactive feedback loop between the actual needs of each patient and the drug products. This review provides an overview of advanced design solutions for new products such as interactive personalized treatment that would interconnect the pharmaceutical and digital worlds. Furthermore, we discuss the recent advancements in the pharmaceutical supply chain (PSC) management and related limitations of the current mass production model. We summarize the current state of the art and envision future directions and potential development areas.
Socioeconomic position and the COVID-19 care cascade from testing to mortality in Switzerland: a population-based analysis
Authors: Julien Riou, Radoslaw Panczak, Christian L Althaus, Christoph Junker, Damir Perisa, Katrin Schneider, Nicola G Criscuolo, Nicola Low, Matthias Egger
Journal: The Lancet Public Health (2021)

The inverse care law states that disadvantaged populations need more health care than advantaged populations but receive less. Gaps in COVID-19-related health care and infection control are not well understood. We aimed to examine inequalities in health in the care cascade from testing for SARS-CoV-2 to COVID-19-related hospitalisation, intensive care unit (ICU) admission, and death in Switzerland, a wealthy country strongly affected by the pandemic.
Abstract 2496: CD82 regulation of c-Met in metastatic prostate cells
Authors: Suganthi Sridhar, Emily Brandes, Patrick Aller, Eddie Barrie
Journal: Cancer Research (2021)

Abstract Metastatic prostate cancer is the second leading cause of cancer deaths among men in the U.S. Metastasis involves regulators, which involve complex cell signaling processes and our current knowledge on how prostate cancer metastasis develops is still under investigation. If these regulators can be identified and the mechanisms fully elucidated, they can be potential targets for oncologic treatment. CD82 (KAI1), a tetraspanin first identified as a metastasis tumor suppressor in prostate cells is one such regulator involved in the metastatic process. Currently, CD82 downregulation is not only observed in prostate but also in a variety of many invasive epithelial tumors which include tumors of the gastric, colon, cervix, breast, skin, bladder, lung, pancreas, liver, and thyroid. CD82 has been well documented as an inhibitor of cell motility and invasion in cancer cells, with varied inhibitory mechanisms. By introducing CD82 in metastatic cell lines (PC3) that do not express CD82, we have shown CD82 to regulate c-Met, a growth factor receptor, a protooncogene that is over expressed and or over activated in prostate tumors. Overactivation of c-Met promotes cell proliferation, migration and invasion. However, it is still not well understood how exactly CD82 regulates c-Met. Using metastatic prostate cell lines (PC3) and comparing them with PC3 clones generated to express CD82, we are using immunofluorescence, immunoprecipitation, flow cytometry, and western blot techniques to analyze the exact mechanism by which CD82 regulates c-Met. Preliminary data indicate CD82 does not colocalize with CD82, nor does it downregulate c-Met expression on the cell surface. However, CD82 expression seems to cause varied distribution of c-Met in the cell and is currently being investigated. Preliminary indications are that CD151, another tetraspanin may be involved in this regulation. CD151 is a known tumor promoter and has been shown to associate with c-Met. Currently, our lab is exploring the redistribution pattern of c-Met upon CD82 expression as a regulatory mechanism, in addition to exploring the CD82 and CD151 expression dynamics as part of or as alternate mechanism to c-Met regulation. The results observed will provide insights into the role CD82 plays in c-Met regulation as well as it may overall play in tumor progression and metastasis in prostate cancer. Notably, the results may also shed more light on CD82 regulation in other tumors where CD82 downregulation is observed. Citation Format: Suganthi Sridhar, Emily Brandes, Patrick Aller, Eddie Barrie. CD82 regulation of c-Met in metastatic prostate cells [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 2496.
Comparison of two techniques for Holmium Laser Enucleation of Prostate (HoLEP): Long-term outcomes and predictive model for symptoms recurrence
Authors: M. Droghetti, L. Bianchi, M.G. Giampaoli, P. Piazza, C. Casablanca, D. Romagnoli, D. D’Agostino, A. Porreca, R. Schiavina
Journal: European Urology (2021)
脳梗塞発症に伴い変化した形態を心エコーで経時的に観察しえたcaseous mitral annular calcificationの1例
Authors: 東晴彦, 大原貴裕, 中谷敏, 北風政史, 橋本修治, 鳥居孝子, 宮下光太郎, 成冨博章
Journal: Circulation (2008)
A Multicenter Randomized Controlled Trial Comparing Two Bowel Cleansing Regimens for Colonoscopy After Failed Bowel Preparation
Authors: Michael S.L. Sey, Daniel Von Renteln, Richard Sultanian, Cassandra McDonald, Mickael Bouin, Nilesh Chande, Amindeep Sandhu, Brian Yan, Myriam Martel, Alan Barkun
Journal: Clinical Gastroenterology and Hepatology (2021)
Post-enucleation morcellation procedure: Lights and shadows
Authors: M. Maltagliati, L. Berti, C. Buizza, L. Rivolta, C. Gastaldi, G. Pedaci, G. Malvestiti, G. Autieri, M.C. Sighinolfi, S. Micali, B. Rocco, G. Bozzini
Journal: European Urology (2021)
Medicare and the Shocking US Food and Drug Administration Approval of Aducanumab
Authors: Francis J. Crosson, Kenneth Covinsky, Rita F. Redberg
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Presence of MDS-Related Cytogenetic Abnormalities Predicts Worse Outcomes in Primary Myelofibrosis Compared to Patients with Del(13q)
Authors: Mohammad Omar Hussaini, Jinming Song, David A Sallman, Eric Padron, Rami S. Komrokji, Andrew Kuykendall, Sayeef Mirza, Ling Zhang
Journal: Blood (2017)
Holmium laser enucleation and water vapor thermal therapy for the treatment of symptomatic benign prostatic hyperplasia: A cost analysis
Authors: M. Baboudjian, M. Fourmarier, C. Alegorides, A. Atamian, A. Atamian, C. Eghazarian, C. Alegorides, M. Fourmarier
Journal: European Urology (2021)
Mitral Annular Dynamics in AF Versus Sinus Rhythm
Authors: Sébastien Deferm, Philippe B. Bertrand, David Verhaert, Frederik H. Verbrugge, Jeroen Dauw, Kevin Thoelen, Alexander Giesen, Liesbeth Bruckers, Filip Rega, James D. Thomas, Robert A. Levine, Pieter M. Vandervoort
Journal: JACC. Cardiovascular imaging (2021)
Rehabilitation Intervention in Older Patients With Acute Heart Failure With Preserved Versus Reduced Ejection Fraction
Authors: Robert J. Mentz, David J. Whellan, Gordon R. Reeves, Amy M. Pastva, Pamela Duncan, Bharathi Upadhya, M. Benjamin Nelson, Haiying Chen, Shelby D. Reed, Paul B. Rosenberg, Alain G. Bertoni, Christopher M. O’Connor, Dalane W. Kitzman
Journal: JACC Heart Failure (2021)
Response to: ‘Correspondence on ‘Role of joint damage, malalignment and inflammation in articular tenderness in rheumatoid arthritis, psoriatic arthritis and osteoarthritis’’ by Dumoulin<i>et al</i>
Authors: Irina Gessl, Daniel Aletaha, Peter Mandl
Journal: Annals of the Rheumatic Diseases (2021)

Response to: 'Correspondence on 'Role of joint damage, malalignment and inflammation in articular tenderness in rheumatoid arthritis, psoriatic arthritis and
Multiplex Tissue Imaging Harmonization: A Multicenter Experience from CIMAC-CIDC Immuno-Oncology Biomarkers Network
Authors: Guray Akturk, Edwin R. Parra, Evisa Gjini, Ana Lako, J. Jack Lee, Donna Neuberg, Jiexin Zhang, Shen Yao, Ilaria Laface, Anita Rogic, Pei-Hsuan Chen, Beatriz Sanchez-Espiridion, Diane M. Del Valle, Radim Moravec, Robert Kinders, Courtney Hudgens, Catherine Wu, Ignacio I. Wistuba, Magdalena Thurin, Stephen M. Hewitt, Scott Rodig, Sacha Gnjatic, Michael T. Tetzlaff
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The Cancer Immune Monitoring and Analysis Centers – Cancer Immunologic Data Commons (CIMAC-CIDC) network supported by the NCI Cancer Moonshot initiative was established to provide correlative analyses for clinical trials in cancer immunotherapy, using state-of-the-art technology. Fundamental to this initiative is implementation of multiplex IHC assays to define the composition and distribution of immune infiltrates within tumors in the context of their potential role as biomarkers. A critical unanswered question involves the relative fidelity of such assays to reliably quantify tumor-associated immune cells across different platforms. Experimental Design: Three CIMAC sites compared across their laboratories: (i) image analysis algorithms, (ii) image acquisition platforms, (iii) multiplex staining protocols. Two distinct high-dimensional approaches were employed: multiplexed IHC consecutive staining on single slide (MICSSS) and multiplexed immunofluorescence (mIF). To eliminate variables potentially impacting assay performance, we completed a multistep harmonization process, first comparing assay performance using independent protocols followed by the integration of laboratory-specific protocols and finally, validating this harmonized approach in an independent set of tissues. Results: Data generated at the final validation step showed an intersite Spearman correlation coefficient (r) of ≥0.85 for each marker within and across tissue types, with an overall low average coefficient of variation ≤0.1. Conclusions: Our results support interchangeability of protocols and platforms to deliver robust, and comparable data using similar tissue specimens and confirm that CIMAC-CIDC analyses may therefore be used with confidence for statistical associations with clinical outcomes largely independent of site, antibody selection, protocol, and platform across different sites.
Abstract 2353: Metabolic reprogramming by SLC1A5 downregulation in pancreatic cancer cells
Authors: Raj Kumar Sharma, Balalji Krishnamachary, Ishwarya Sivakumar, Yelena Mironchik, Santosh Kumar Bharti, Zaver M. Bhujwalla
Journal: Cancer Research (2021)

Abstract Introduction: Pancreatic cancers exhibit limited response to chemo- and radiation therapy. Identifying novel targets for pancreatic cancer treatment is important for new treatment strategies. Because pancreatic cancer cells are ‘glutamine avid' [1], targeting glutamine metabolic pathways can provide novel options for treatment. The glutamine transporter, SLC1A5, is being actively investigated as a pharmacological target in cancer [2]. Here we have engineered human pancreatic cells expressing shRNA to downregulate the glutamine transporter SLC1A5. We performed high-resolution 1H magnetic resonance spectroscopy (MRS) to understand the metabolic reprograming that occurs with SLC1A5 downregulation in these two cell lines. Method: Panc1 and Pa04C pancreatic cancer cell lines were genetically engineered to express shRNA against SLC1A5 using lentiviral transduction. Downregulation of SLC1A5 was verified with qRTPCR and immunoblotting. Control cells expressing an empty vector (EV) were also engineered. Dual phase extraction was performed as previously described [3]. High-resolution 1H MRS was performed on the aqueous phase extracts and recorded on a 750 MHz spectrometer. All data acquisition, processing and quantification was performed with TOPSPIN 3.5 software. Spectra were obtained from Panc1EV (n=4), Pa04CEV (n=4), Panc1_SLC1A5_shRNA (n=4) and Pa04C_SLC1A5_shRNA (n=4) cells. Results and Discussion: SLC1A5 downregulation significantly decreased the glutamine/glutamate ratio in Pa04C_SLC1A5_shRNA cells but not in Panc1_SLC1A5_shRNA cells. Instead, in Panc1_SLC1A5_shRNA cells, a significant decrease of the amino acids leucine, isoleucine, valine, tyrosine, histidine, and phenylalanine was observed. Lactate and fumarate also significantly decreased in Panc1_SLC1A5_shRNA cells. Other than the significant decrease of glutamine/glutamate in the Pa04C_SLC1A5_shRNA cells, no other significant metabolic differences were observed in these cells. Our data expand the understanding of the diverse metabolic reprogramming that occurs following SLC1A5 downregulation in two human pancreatic cancer cell lines that may lead to the development of additional metabolic targets. Supported by NIH R01CA193365 and R35CA209960.1. Son J et al., Nature. 2013; 2. Bhutia YD et al., Biochim Biophys Acta. 2016; 3. Winnard PT Jr. et al., J Cachexia Sarcopenia Muscle. 2020. Citation Format: Raj Kumar Sharma, Balalji Krishnamachary, Ishwarya Sivakumar, Yelena Mironchik, Santosh Kumar Bharti, Zaver M. Bhujwalla. Metabolic reprogramming by SLC1A5 downregulation in pancreatic cancer cells [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 2353.