tbuckley/cabot-search huggingface dataset:
Abstract 3679: Klotho suppresses colon cancer through modulation of the Wnt pathway and unfolded protein response
Authors: Tami Rubinek, Tammi Rubinstein, Shiri Shahmoon, Chen Varol, Ehud Zigmond, Rina Rosin-Absesfelf, Iris Barshack, Ido Wolf
Journal: Cancer Research (2016)

Abstract Aberrant activation of the canonical Wnt pathway is implicated in colorectal cancer (CC) development and progression. β-catenin, the key effector of this pathway, functions with T-cell factor/lymphoid-enhancer-factor (TCF/LEF) to activate expression of Wnt target genes. Klotho is a transmembrane protein, which can be shed and act as a circulating hormone. Klotho-deficient mice manifest a syndrome resembling accelerated aging, while klotho overexpression extends life span. We previously identified klotho as a breast and pancreatic tumor suppressor (TS). Recent data indicate klotho as a TS in an array of malignancies, including CC. Among other activities, klotho inhibits the insulin-like growth factor (IGF)-1 and Wnt pathways. We aimed to decipher the role of klotho as a TS in CC. We first noted that klotho overexpression inhibited CC cell colony formation. Next, we examined in vivo effects using the azoxymethane mouse model, and found that klotho inhibited colon polyp formation. We then used an orthotopic model by injecting MC38 cells to mice colons, and found that klotho inhibited colonic obstruction and tumor formation. While we did not see an effect of klotho on the IGF-1 pathway, klotho did affect the Wnt pathway. Klotho reduced Wnt3A and β-catenin levels as measured by Western blotting, and inhibited TFC/LEF transcriptional activation in luciferase assay. As transcriptional inhibition was abrogated by a constitutively active β-catenin, we suspected that klotho inhibited the pathway upstream of β-catenin. Indeed, co-immunoprecipitation analyses indicated direct interaction between klotho and Wnt3A. As the inhibitory effect of klotho on CC cell colony formation was only partially rescued by a constitutively active β-catenin, additional mechanisms may be involved. Thus, we conducted a cDNA expression microarray and involvement of klotho in endoplasmic reticulum (ER) stress and unfolded protein response (UPR) was observed. Further studies showed that klotho induced elevation in XBP1 RNA, GRP78 protein levels, and eIF2α phosphorylation, all indicative of a role klotho plays in UPR regulation. Our data indicate klotho as a potent TS in CC, and suggest its role at early stages of tumor formation. The Wnt pathway partially mediates klotho effects in CC, however additional mechanisms, including ER stress response regulation, are involved. Citation Format: Tami Rubinek, Tammi Rubinstein, Shiri Shahmoon, Chen Varol, Ehud Zigmond, Rina Rosin-Absesfelf, Iris Barshack, Ido Wolf. Klotho suppresses colon cancer through modulation of the Wnt pathway and unfolded protein response. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3679.
Tetracycline-inducible mouse U6 vector for conditional expression of shRNA
Authors: Milind Suraokar, Jeri Kim, Norma Llansa, Gabriella Mendosa, Christopher J. Logothetis, Scott M. Lippman, David G. Menter
Journal: Cancer Research (2005)

5442  The phenomenon of RNA interference (RNAi) in mammalian cells allows for the use of small double-stranded RNA molecules (siRNA) to disrupt the translation of homologous mRNA and consequently the expression of genes. An added advantage to this powerful technology would be the use of an inducible promoter to produce the shRNA in a conditional manner. We have generated a tetracycline-inducible version of the mouse U6 promoter that is normally shutdown in the presence of the Tet repressor but on doxycycline treatment, is de-repressed to transcribe the siRNA molecules, which subsequently induces knock down of the related gene. We are currently using this system along-with a Tet operon containing human U6 promoter to selectively diminish the presence of selenoproteins in mouse and human cells. It has been postulated that the redox function of the selenoproteins is responsible for the protective effect of selenium (Se) in prostate cancer. Selenoprotein synthesis requires the concerted co-translational action of elongation factor (mSelB) and the SECIS-binding protein-2 (SBP2). Removal of these molecules will eliminate selenoprotein function in a cell. We have designed mouse and human siRNA oligoes directed against SBP2 and mSelB message. These are being cloned into the siRNA vector containing the inducible mouse/human U6 promoter along-with a puromycin selectable cassette, and would be transfected into the human (normal and prostate cancer) cells and mouse (TRAMP) cells stably transfected with a Tet repressor construct. On doxycycline treatment the siRNA targeted against SBP2 and mSelB message would be produced and subsequently these cells will be analyzed for altered growth dynamics and changes in signal transduction or gene activity due to the knockdown of selenoproteins. Thus this inducible approach to generate shRNA will enable targeting of gene expression in mouse cells in a temporally controlled manner.
Can Adjunctive Pharmacotherapy Reduce Hospitalization in Schizophrenia?
Authors: Donald C. Goff
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Active Calpain Promotes Fibrin Clot Contraction By Strengthening the Coupling of Fibrin-Bound αIIbβ3 to the Platelet Cytoskeleton
Authors: Rustem I. Litvinov, Karen Pei Yi Fong, Oleg V. Kim, Kathleen I. Molnar, Paul C. Billings, Alex Sternisha, James A. Wells, John W. Weisel, William F. DeGrado, Joel S. Bennett
Journal: Blood (2018)
IMMU-68. REMODELING IMMUNITY AGAINST MEDULLOBLASTOMA VIA RNA-LOADED NANOPARTICLES
Authors: Elias Sayour, Gabriel De Leon, Adam Grippin, Catherine Flores, Christina Pham, Duane Mitchell
Journal: Neuro-Oncology (2017)

While recurrent medulloblastoma (MB) remains almost uniformly fatal, our group has shown a trend (p=0.07) toward improved survival in patients receiving autologous tumor RNA pulsed dendritic cells (DCs) coupled with ex vivo expanded total RNA activated T-cells. However, the advancement of autologous cellular therapeutics through the commercialization pipeline has been encumbered by significant cost, complexity and time to generation. To circumvent these challenges, we developed a novel treatment platform, which leverages the use of commercially available and clinically translatable nanoparticles (NPs) that can be combined with tumor-derived RNA to systemically activate peripheral immunity against MB antigens. To overcome the limitations of poorly immunogenic local vaccination strategies, we assessed if intravenous delivery of tumor-derived RNA encapsulated in lipophilic NPs could systemically activate antigen presenting cells (APCs) for induction of therapeutic anti-tumor immunity in pre-clinical MB models. We identified a clinically translatable NP formulation for the delivery of RNA to APCs that induces in vivo gene expression and preserves RNA stability over time. When administered intravenously, RNA-NPs lead to systemic activation (i.e. MHCI/II, CD40, CCR7 and CD86) of host APCs within lymphoid organs and within the intratumoral microenvironment. We demonstrated that both model-antigen encoding RNA and physiologically-relevant tumor-derived RNA, when encapsulated in NPs, could expand potent anti-tumor T-cell immunity. T-cell immunity elicited by RNA-NPs was superior to peptide vaccines formulated in complete Freund’s adjuvant. We enhanced the immunogenicity of this platform by simply combining mRNAs encoding for immunomodulatory molecules (i.e. HCV-PAMPs, GM-CSF). In a pre-clinical cellular immunotherapy model targeting an anaplastic murine MB, RNA NPs supersede DCs in mediating anti-tumor activity. Since RNA-NPs bypass cost/complexity of cellular therapeutics, are amenable to central distribution, and can be made within days of tumor-resection, these formulations supplant DCs by providing near-immediate immune induction for patients with recurrent MBs.
Abstract 167: EMS Provider Documentation Changes the Predictive Value of Bystander CPR
Authors: Lars Wik, Jan-Aage Olsen, David Persse, Fritz Sterz, Michael Lozano, Marc A Brouwer, Mark Westfall, Chris M Souders, Reinhard Malzer, Pierre M van Grunsven, David T Travis, Ulrich R Herken, E Brooke Lerner
Journal: Circulation (2013)

Background: It is accepted that bystander CPR improves survival from out-of-hospital cardiac arrest (OHCA). The Utstein template advocates for collection of bystander CPR data. The Circulation Impr...
Staphylococcus aureus Leukocidins Target Endothelial DARC to Cause Lethality in Mice
Authors: Ashira Lubkin, Warren L. Lee, Francis Alonzo, Changsen Wang, Jason Aligo, Matthew Keller, Natasha M. Girgis, Tamara Reyes-Robles, Rita Chan, Aidan O’Malley, Peter Buckley, Nikollaq Vozhilla, Marilyn T. Vasquez, Johnny Su, Michael Sugiyama, Stephen T. Yeung, Maryaline Coffre, Sofia Bajwa, Eric Chen, Patricia Martin, Sang Y. Kim, Cynthia Loomis, G. Scott Worthen, Bo Shopsin, Kamal M. Khanna, Daniel Weinstock, Anthony Simon Lynch, Sergei B. Koralov, P'ng Loke, Ken Cadwell, Victor J. Torres
Journal: Cell Host & Microbe (2019)
Structural diversity of the cardenolide calotropin renders it as a targeted therapy for harnessing TNBC progression through tuning nitric oxide (NO) levels
Authors: R.A. El-Layeh, R.A. Youness, H. Askary, A. Abdelmotaal, R.A. Assal
Journal: Annals of Oncology (2019)

Background: Triple negative breast cancer (TNBC) is the most aggressive breast cancer (BC) subtype. It has the worst prognosis, highest recurrence and metastatic rates. Due to the clinical and molecular heterogeneity of TNBC, there is an emerging need to identify new molecular therapeutic targets. Nitric oxide (NO) has a dual role in cancer depending on its levels. At low concentrations, NO promotes tumor growth, while at high concentrations, NO has an anti-neoplastic function. Natural compounds have emerged as signaling pathways' regulators in various tumors. Cardenolides specifically have potent cytotoxic effects in different cancers as lung and liver cancer. Our group has isolated the cardenolides, Calotropin and 7,8-dehydrocalotropin from Calotropisgigantea (L.) Dryand (Apocyanaceae). Calotropin showed potent cytotoxicy against non-small cell lung cancer, glioblastoma and prostate cancer, but has never been investigated against BC. Our aim was to investigate the anticancer effects of the isolated compounds on MDA-MB-231 TNBC cells by functional characterization and unravel their role in regulating NO levels in BC. Methods: MDA-MB-231 cells were treated with serial dilutions (1, 5, 10, 20, 60 and 100 μM) of calotropin and 7,8-dehydrocalotropin. Their cytotoxic activities were assessed using MTT for cellular viability and IC50 values were obtained. Cellular migration and colony forming ability were measured using scratch and colony forming assays, respectively. NO production was measured using Greiss reagent. Results: Both calotropin and 7,8-dehydrocalotropin were able to decrease cellular viability, migration and colony formation of MDA-MB-231 cells in a dose-dependent manner. Calotropin reduced NO levels in MDA-MB-231 cells. However 7,8-dehydrocalotropin did not have any significant effects in regulating NO. Conclusions: Calotropin showed more potent cytotoxicity on MDA-MB-231 cells compared to 7,8-dehydrocalotropin. Calotropin acts as a negative regulator of NO production, whereas 7,8-dehydrocalotropin failed to regulate NO production. This could be attributed to the structural difference between both compounds. Thus calotropin can be developed as a targeted therapy against BC. Legal entity responsible for the study: German University of Cairo. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
The Need for Greater Rigor in Childhood Nutrition and Obesity Research
Authors: Alexis C. Wood, Jonathan D. Wren, David B. Allison
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Disulfide-bond A oxidoreductase-like protein protects against ectopic fat deposition and lipid-related kidney damage in diabetic nephropathy
Authors: Xianghui Chen, Yachun Han, Peng Gao, Ming Yang, Li Xiao, Xiaofen Xiong, Hao Zhao, Chengyuan Tang, Guochun Chen, Xuejing Zhu, Shuguang Yuan, Fuyou Liu, Lily Q. Dong, Feng Liu, Yashpal S. Kanwar, Lin Sun
Journal: Kidney International (2019)
A Review of the Role of Breast Arterial Calcification for Cardiovascular Risk Stratification in Women
Authors: Quan M. Bui, Lori B. Daniels
Journal: Circulation (2019)

Cardiovascular disease continues to be the leading cause of death among women in the United States. One of the barriers to improving cardiovascular disease outcomes in women is the lack of reliable, effective screening modalities. Breast arterial calcification has emerged as a potential risk stratification tool. Localized deposition in the media of the artery, known as Mönckeberg medial calcific sclerosis, is notably different from the intimal atherosclerotic process commonly associated with coronary artery disease. Nonetheless, studies favor a correlation between breast arterial calcification and cardiovascular risk factors or coronary artery disease, defined as coronary artery calcification on computed tomography scan or both nonobstructive and obstructive lesions on angiography. Since a majority of women over the age of 40 undergo yearly breast cancer screening with mammography, measurement of breast arterial calcification may offer a personalized, noninvasive approach to risk-stratify women for cardiovascular disease at no additional cost or radiation. Mammography has the potential to alter the course of the leading cause of death in women, heart disease, through the evaluation of breast arterial calcification and identification of opportunities for prevention. Current evidence supports the universal reporting of breast arterial calcifications and personalized patient-provider discussions to more aggressively treat cardiac risk factors through targeted medical therapies or healthy lifestyle changes.
Summary of notifiable diseases - United States, 2000.
Authors: S. L. Groseclose, W. S. Brathwaite, P. A. Hall, C. M. Knowles, D. A. Adams, F. Connor, M. Hester, P. Sharp, W. J. Anderson, R. F. Fagan, J. J. Aponte, G. F. Jones, D. A. Nitschke, J. Vaughan, C. A. Worsham, M. H. Chang, T. Doyle, R. A. Jajosky
Journal: MMWR Morbidity and Mortality Weekly Report (2000)
Closing the Gap — Making Medical School Admissions More Equitable
Authors: Efrain Talamantes, Mark C. Henderson, Tonya L. Fancher, Fitzhugh Mullan
Journal: New England Journal of Medicine (2019)

The growing gap between the racial, ethnic, and socioeconomic makeup of medical school classes and that of the general population means medical education is slipping further out of reach for many poor and minority students.
Results from a Prospective Real World Study Show Strong Efficacy of Idelalisib in CLL, Including High-Risk CLL, and Provide Evidence That Pjp Prophylaxis Positively Impacts on Overall Survival
Authors: Manuela Hoechstetter, Philipp Eissmann, Nike Hucke, Anna van Troostenburg, Heribert Ramroth, Wolfgang Knauf
Journal: Blood (2018)
Management of perinatal depression with non-drug interventions
Authors: Sara L Johansen, Thalia K Robakis, Katherine Ellie Williams, Natalie L Rasgon
Journal: BMJ (2019)

Perinatal depression is a common disorder that has been associated with serious risks to mother and child. Recently, screening for depression in pregnant and postpartum women has increased, as has the development of new psychotherapy and non-drug treatment modalities. Matching patients to treatments can be challenging, and although research into personalized treatment of major depression in the general population has increased, no published guidelines focus on personalized treatment approaches to perinatal depression. In particular, guidelines on non-drug treatments are lacking. This review summarizes the evidence on personalized non-drug treatment of perinatal depression, how to incorporate patients' preferences, novel treatments under investigation, and the potential role of biomarkers in matching patients to treatment. The review provides recommendations for future research in personalized care of perinatal depression.
DNA Damage Response Mediates Pressure Overload–Induced Cardiomyocyte Hypertrophy
Authors: Yuji Nakada, Ngoc Uyen Nhi Nguyen, Feng Xiao, Jainy J. Savla, Nicholas T. Lam, Salim Abdisalaam, Souparno Bhattacharya, Shibani Mukherjee, Aroumougame Asaithamby, Thomas G. Gillette, Joseph A. Hill, Hesham A. Sadek
Journal: Circulation (2019)
Information for Readers
Authors: Elaine S. Williams
Journal: JAMA (1995)

We hereby thank the 3023 peer reviewers who completed<i>JAMA</i>manuscript reviews in 1994 and whose names appear on pages 1309-1316. In 1994, it took a median of 17 calendar days from manuscript receipt to rejection, 85 days from receipt to acceptance, and 181 days from receipt to publication. A mean of 26 days was required for each peer review; each reviewer handled a mean of 1.6 manuscripts. Forty-five percent of the 4107 manuscripts we received in 1994 were sent for outside review, most often to three reviewers. Forty-nine
Systematic Evaluation of Patient-Reported Outcome Protocol Content and Reporting in Cancer Trials
Authors: Derek Kyte, Ameeta Retzer, Khaled Ahmed, Thomas Keeley, Jo Armes, Julia M Brown, Lynn Calman, Anna Gavin, Adam W Glaser, Diana M Greenfield, Anne Lanceley, Rachel M Taylor, Galina Velikova, Michael Brundage, Fabio Efficace, Rebecca Mercieca-Bebber, Madeleine T King, Grace Turner, Melanie Calvert
Journal: JNCI Journal of the National Cancer Institute (2019)

Patient-reported outcomes (PROs) are captured within cancer trials to help future patients and their clinicians make more informed treatment decisions. However, variability in standards of PRO trial design and reporting threaten the validity of these endpoints for application in clinical practice.We systematically investigated a cohort of randomized controlled cancer trials that included a primary or secondary PRO. For each trial, an evaluation of protocol and reporting quality was undertaken using standard checklists. General patterns of reporting where also explored.Protocols (101 sourced, 44.3%) included a mean (SD) of 10 (4) of 33 (range = 2-19) PRO protocol checklist items. Recommended items frequently omitted included the rationale and objectives underpinning PRO collection and approaches to minimize/address missing PRO data. Of 160 trials with published results, 61 (38.1%, 95% confidence interval = 30.6% to 45.7%) failed to include their PRO findings in any publication (mean 6.43-year follow-up); these trials included 49 568 participants. Although two-thirds of included trials published PRO findings, reporting standards were often inadequate according to international guidelines (mean [SD] inclusion of 3 [3] of 14 [range = 0-11]) CONSORT PRO Extension checklist items). More than one-half of trials publishing PRO results in a secondary publication (12 of 22, 54.5%) took 4 or more years to do so following trial closure, with eight (36.4%) taking 5-8 years and one trial publishing after 14 years.PRO protocol content is frequently inadequate, and nonreporting of PRO findings is widespread, meaning patient-important information may not be available to benefit patients, clinicians, and regulators. Even where PRO data are published, there is often considerable delay and reporting quality is suboptimal. This study presents key recommendations to enhance the likelihood of successful delivery of PROs in the future.
The DNA modification N6-methyl-2’-deoxyadenosine (m6dA) drives activity-induced gene expression and is required for fear extinction
Authors: Xiang Li, Qiongyi Zhao, Wei Wei, Quan Lin, Christophe Magnan, Michael R. Emami, Luis E. Wearick-Silva, Thiago W. Viola, Paul R. Marshall, Jiayu Yin, Sachithrani U. Madugalle, Ziqi Wang, Sarah Nainar, Cathrine Broberg Vågbø, Laura J. Leighton, Esmi L. Zajaczkowski, Ke Ke, Rodrigo Grassi-Oliveira, Magnar Bjørås, Pierre F. Baldi, Robert C. Spitale, Timothy W. Bredy
Journal: Nature Neuroscience (2019)