tbuckley/cabot-search huggingface dataset:
Genetic editing of colonic organoids provides a molecularly distinct and orthotopic preclinical model of serrated carcinogenesis
Authors: Tamsin R M Lannagan, Young K Lee, Tongtong Wang, Jatin Roper, Mark L Bettington, Lochlan Fennell, Laura Vrbanac, Lisa Jonavicius, Roshini Somashekar, Krystyna Gieniec, Miao Yang, Jia Q Ng, Nobumi Suzuki, Mari Ichinose, Josephine A Wright, Hiroki Kobayashi, Tracey L Putoczki, Yoku Hayakawa, Simon J Leedham, Helen E Abud, Ömer H Yilmaz, Julie Marker, Sonja Klebe, Pratyaksha Wirapati, Siddhartha Mukherjee, Sabine Tejpar, Barbara A Leggett, Vicki L J Whitehall, Daniel L Worthley, Susan L Woods
Journal: Gut (2018)

Objective Serrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated kinase pathway gene, BRAF , and epigenetic modifications termed the CpG Island Methylator Phenotype, leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein. Design We use organoid culture combined with CRISPR/Cas9 genome engineering to sequentially introduce genetic alterations associated with serrated CRC and which regulate the stem cell niche, senescence and DNA mismatch repair. Results Targeted biallelic gene alterations were verified by DNA sequencing. Organoid growth in the absence of niche factors was assessed, as well as analysis of downstream molecular pathway activity. Orthotopic engraftment of complex organoid lines, but not Braf V600E alone, quickly generated adenocarcinoma in vivo with serrated features consistent with human disease. Loss of the essential DNA mismatch repair enzyme, Mlh1, led to microsatellite instability. Sphingolipid metabolism genes are differentially regulated in both our mouse models of serrated CRC and human CRC, with key members of this pathway having prognostic significance in the human setting. Conclusion We generate rapid, complex models of serrated CRC to determine the contribution of specific genetic alterations to carcinogenesis. Analysis of our models alongside patient data has led to the identification of a potential susceptibility for this tumour type.
Abstract #2762: RAD001 (everolimus) suppresses growth of a gastric MALT lymphoma cell Line via downregulation of pAKT/mTOR and BAFF/NF-\#954;B signal transduction pathways
Authors: Sung-Hsin Kuo, Ping-Ning Hsu, Kun-Huei Yeh, Pei-Yen Yeh, Li-Tzong Chen, Wei-Chen Cheng, Chih-Hung Hsu, Ann-Lii Cheng
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Background: We have recently uncovered that BAFF expression is closely associated with H. pylori -independent growth of gastric MALT lymphoma (Blood 2008;112:2927-34). mTOR inhibitor has recently emerged as an important new class of drugs that are active in the treatment of lymphoma. In this study, we sought to examine whether RAD001, an mTOR inhibitor, can be effective in the treatment of H. pylori -independent gastric MALT lymphoma. Methods: The primary MALT lymphoma cell was obtained from fresh marrow aspiration-derived lymphoma tissues of a t(11;18)(q21;q21)- and t(1;14)(p22;q32)- negative H. pylori -independent gastric MALT lymphoma patient who had failed chemotherapy. The cell cycle phase was analyzed by flow cytometry. Expression of pAKT (Ser473 and Thr308), p-p70S6K, p-4E-BP1, p-mTOR, p-eIF4E, cyclin A, cyclin D3, BCL10, BCL3, NF-\#954;B (p65), c-Myc, and insulin receptor substrate-1 (IRS-1), and BAFF was measured by immunoblotting. Transactivity of NF-\#954;B was measured by electromobility shift assay. Results: RAD001 blocked cell cycle progression in G0/G1 phase and induced no significant apoptosis in MALT lymphoma cell line with the IC50s of growth suppression less than 50 nM. In parallel with the RAD001-induced growth inhibition, a dose- and schedule- dependent down-regulation of pAKT (Ser473 and Thr308), p-mTOR, p-p70S6K, p-4E-BP1, p-eIF4E, cyclin A, and cyclin D3 was demonstrated. Furthermore, RAD001 also suppressed the expression of c-Myc, TNF-\#945;, and BAFF, and nuclear expression of BCL3 and BCL10, and NF-\#954;B transactivity, but did not affect IRS-1. Conclusions: RAD001 is effective in growth suppression of a H. pylori -independent gastric MALT lymphoma cell line, and the activity is at least partly related to down-regulation of pAKT, mTOR, eIF4E, and BAFF/BCL10/NF-\#954;B signaling pathways.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2762.
Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in the Quest for the Molecules With Therapeutic and Preventive Potential
Authors: Ana Marta de Matos, Maria Paula de Macedo, Amélia Pilar Rauter
Journal: Medicinal Research Reviews (2017)

Abstract Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two age‐related amyloid diseases that affect millions of people worldwide. Broadly supported by epidemiological data, the higher incidence of AD among type 2 diabetic patients led to the recognition of T2D as a tangible risk factor for the development of AD. Indeed, there is now growing evidence on brain structural and functional abnormalities arising from brain insulin resistance and deficiency, ultimately highlighting the need for new approaches capable of preventing the development of AD in type 2 diabetic patients. This review provides an update on overlapping pathophysiological mechanisms and pathways in T2D and AD, such as amyloidogenic events, oxidative stress, endothelial dysfunction, aberrant enzymatic activity, and even shared genetic background. These events will be presented as puzzle pieces put together, thus establishing potential therapeutic targets for drug discovery and development against T2D and diabetes‐induced cognitive decline—a heavyweight contributor to the increasing incidence of dementia in developed countries. Hoping to pave the way in this direction, we will present some of the most promising and well‐studied drug leads with potential against both pathologies, including their respective bioactivity reports, mechanisms of action, and structure–activity relationships.
miR-155 promotes FLT3-ITD–induced myeloproliferative disease through inhibition of the interferon response
Authors: Jared A. Wallace, Dominique A. Kagele, Anna M. Eiring, Carissa N. Kim, Ruozhen Hu, Marah C. Runtsch, Margaret Alexander, Thomas B. Huffaker, Soh-Hyun Lee, Ami B. Patel, Timothy L. Mosbruger, Warren P. Voth, Dinesh S. Rao, Rodney R. Miles, June L. Round, Michael W. Deininger, Ryan M. O’Connell
Journal: Blood (2017)
A dose-dependent plasma signature of the safety and immunogenicity of the rVSV-Ebola vaccine in Europe and Africa
Authors: Angela Huttner, Christophe Combescure, Stéphane Grillet, Mariëlle C. Haks, Edwin Quinten, Christine Modoux, Selidji Todagbe Agnandji, Jessica Brosnahan, Julie-Anne Dayer, Ali M. Harandi, Laurent Kaiser, Donata Medaglini, Tom Monath, Pascale Roux-Lombard, Peter G. Kremsner, Tom H. M. Ottenhoff, Claire-Anne Siegrist
Journal: Science Translational Medicine (2017)

A specific plasma signature reveals the critical role of monocytes in the VSV-vectored Ebola vaccine immunogenicity and safety.
The Second International Congress of Group Psychotherapy
Authors: Berthold Stokvis, Berthold Stokvis, S. Lebovici, Weixman J. Warner, Joshua Bierer, S.H. Foulkes, Samuel B. Hadden, Wilfred C. Hulse, J.L. Moreno, S.R. Slavson, Zerka T. Moreno, R. Schindler, Berthold Stokvis, H.R. Teirich, F. Tosquelles, R. Gentis, M. Enkin, F. Bonnet
Journal: Psychotherapy and Psychosomatics (1959)
Erratum: Role of nitric oxide in vascular permeability after combined burns and smoke inhalation injury (American Journal of Respiratory and Critical Care Medicine (2001) 163 (745-752))
Authors: K. Soejima, L. D. Traber, F. C. Schmalstieg, H. Hawkins, J. M. Jodoin, Csaba Szabo, E. Szabo, L. Virag, A. Salzman, D. L. Traber
Journal: American Journal of Respiratory and Critical Care Medicine (2001)
Obesity and Cesarean Section
Authors: Chika Edward Uzoigwe, Kenneth Jose Porter, Luis Carlos Sanchez Franco
Journal: JAMA Pediatrics (2017)

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
<i>PIK3CA</i> Mutations Contribute to Acquired Cetuximab Resistance in Patients with Metastatic Colorectal Cancer
Authors: Jian-Ming Xu, Yan Wang, You-Liang Wang, Yan Wang, Tao Liu, Ming Ni, Man-Sheng Li, Li Lin, Fei-Jiao Ge, Chun Gong, Jun-Yan Gu, Ru Jia, He-Fei Wang, Yu-Ling Chen, Rong-Rui Liu, Chuan-Hua Zhao, Zhao-Li Tan, Yang Jin, Yun-Ping Zhu, Shuji Ogino, Zhi-Rong Qian
Journal: Clinical Cancer Research (2017)

Purpose: Mutations in KRAS are considered to be the main drivers of acquired resistance to epidermal growth factor receptor (EGFR) blockade in patients with metastatic colorectal cancer (mCRC). However, the potential role of other genes downstream of the EGFR signaling pathway in conferring acquired resistance has not been extensively investigated.Experimental Design: Using circulating tumor DNA (ctDNA) from patients with mCRC and with acquired cetuximab resistance, we developed a targeted amplicon ultra-deep sequencing method to screen for low-abundance somatic mutations in a panel of genes that encode components of the EGFR signaling pathway. Mutations with significantly increased variant frequencies upon disease progression were selected by using quartile analysis. The functional consequences of the identified mutations were validated in cultured cells.Results: We analyzed 32 patients with acquired cetuximab resistance in a development cohort. Of them, seven (22%) carried five novel PIK3CA mutations, whereas eight (25%) carried previously reported KRAS mutations. Functional studies showed that novel PIK3CA mutations (all in exon 19; p.K944N, p.F930S, p.V955G, p.V955I, and p.K966E) promote cell viability in the presence of cetuximab. Only one novel PIK3CA mutation (p.K944N) was verified in one of the 27 patients with acquired resistance in a validation cohort, simultaneous KRAS and PIK3CA hotspot mutations were detected in two patients. Among the above 59 acquired resistance patients, those with PIK3CA or RAS mutations detected in ctDNA showed a pronounced decrease in progression-free survival than patients with no mutation.Conclusions: The PIK3CA mutations may potentially contribute to acquired cetuximab resistance in patients with mCRC. Clin Cancer Res; 23(16); 4602-16. ©2017 AACR.
Periodontal disease and the special needs patient
Authors: Louise F. Brown, Pauline J. Ford, Anne L. Symons
Journal: Periodontology 2000 (2017)

Abstract Individuals with special needs are at more risk of dental disease, including periodontal diseases, and have a greater prevalence and incidence of periodontal diseases than the rest of the population. Genetic or medical conditions, and/or the use of prescription medication or recreational substances, may further increase the risk for susceptibility to periodontal disease. The success of preventing or controlling periodontal diseases amongst this group of patients has not been established. Even those individuals who access regular and comprehensive dental care appear to develop periodontal diseases as they age, and this development occurs at a rate comparable to the natural history of the disease. The reasons behind the lack of success of interventions in reducing the incidence of periodontal diseases are complex and part of the lack of success may relate to the professional challenges in treating individuals with special needs.
TCTAP C-242 Successful Trans-collateral Approach for Chronic Total Occlusion of the Superficial Femoral Artery Using a Side-hole Sheath
Authors: Yasuhiro Takahashi, Reiko Shiomura, Erito Furuse, Junya Matsuda, Taisuke Sato, Wataru Shimizu
Journal: Journal of the American College of Cardiology (2017)
Meta-analysis of the correlation between the rs17401966 polymorphism in kinesin family member 1B and susceptibility to hepatitis B virus related hepatocellular carcinoma
Authors: Mingkuan Su, Jianfeng Guo, Jiancheng Huang
Journal: Clinical and Molecular Hepatology (2017)

Background/Aims The association between the kinesin family member 1B (KIF1B) gene polymorphism and the risk of hepatitis B virus-related hepatocellular carcinoma (HCC) has been investigated in many peer-reviewed studies. However, scholars have failed to replicate these results in validation tests. The purpose of the present study was to explore whether the KIF1B rs17401966 polymorphism was associated with susceptibility to HCC. Methods The results of case-controlled studies on the correlation between the KIF1B rs17401966 polymorphism and HCC susceptibility were collected using Google Scholar and the EMBASE, PubMed and CNKI databases. Based on inclusion and exclusion criteria, 5 papers with a total of 12 cohorts were included in this study. Results The 12 cohorts were integrated, and the results showed that the rs17401966 polymorphism reduced the risk for HCC under the allele, heterozygous, homozygous, and dominant models but not under the additive or recessive models. Moreover, the merged results showed strong heterogeneity, and the cumulative meta-analysis results were unreliable. A genetic differentiation analysis of the 12 cohorts found different degrees of genetic differentiation between the 5 cohorts in Zhang et al.'s study and the cohorts in the other studies. We further divided the 12 study cohorts into 2 subgroups based on fixation index value; however, the results of that analysis were inconsistent. Conclusions The results of this meta-analysis were not able to verify the association between the KIF1B rs1740199 polymorphism and HCC risk. Therefore, a well-designed, large-scale, multicenter validation study is needed to confirm the relationship. Keywords: Single nucleotide polymorphism; Hepatitis B virus; Hepatocellular carcinoma; Meta-analysis
Learning Non-rigid Deformations for Robust, Constrained Point-based Registration in Image-Guided MR-TRUS Prostate Intervention
Authors: John A. Onofrey, Lawrence H. Staib, Saradwata Sarkar, Rajesh Venkataraman, Cayce B. Nawaf, Preston C. Sprenkle, Xenophon Papademetris
Journal: Medical Image Analysis (2017)
Notice of Retraction and Replacement: Oostdijk et al. Effects of Decontamination of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUs: A Randomized Clinical Trial. <i>JAMA</i>. 2014;312(14):1429-1437.
Authors: Evelien A. N. Oostdijk, Jozef Kesecioglu, Marcus J. Schultz, Caroline E. Visser, Evert de Jonge, Einar H. R. van Essen, Alexandra T. Bernards, Ilse Purmer, Roland Brimicombe, Dennis Bergmans, Frank van Tiel, Frank H. Bosch, Ellen Mascini, Arjanne van Griethuysen, Alexander Bindels, Arjan Jansz, Fred (A.) L. van Steveninck, Wil C. van der Zwet, Jan Willem Fijen, Steven Thijsen, Remko de Jong, Joke Oudbier, Adrienne Raben, Eric van der Vorm, Mirelle Koeman, Philip Rothbarth, Annemieke Rijkeboer, Paul Gruteke, Helga Hart, Paul Peerbooms, Lex J. Winsser, Anne-Marie W. van Elsacker-Niele, Kees Demmendaal, Afke Brandenburg, Anne Marie G. A. de Smet, Marc J. M. Bonten
Journal: JAMA (2017)

Notice of Retraction and Replacement: Oostdijk et al. Effects of Decontamination of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUs: A Randomized Clinical Trial. JAMA. 2014;312(14):1429-1437.
Infarcted Myocardium-Primed Dendritic Cells Improve Remodeling and Cardiac Function After Myocardial Infarction by Modulating the Regulatory T Cell and Macrophage Polarization
Authors: Eun Ho Choo, Jun-Ho Lee, Eun-Hye Park, Hyo Eun Park, Nam-Chul Jung, Tae-Hoon Kim, Yoon-Seok Koh, Eunmin Kim, Ki-Bae Seung, Cheongsoo Park, Kwan-Soo Hong, Kwonyoon Kang, Jie-Young Song, Han Geuk Seo, Dae-Seog Lim, Kiyuk Chang
Journal: Circulation (2017)

Inflammatory responses play a critical role in left ventricular remodeling after myocardial infarction (MI). Tolerogenic dendritic cells (tDCs) can modulate immune responses, inducing regulatory T cells in a number of inflammatory diseases.We generated tDCs by treating bone marrow-derived dendritic cells with tumor necrosis factor-α and cardiac lysate from MI mice. We injected MI mice, induced by a ligation of the left anterior descending coronary artery in C57BL/6 mice, twice with tDCs within 24 hours and at 7 days after the ligation.In vivo cardiac magnetic resonance imaging and ex vivo histology confirmed the beneficial effect on postinfarct left ventricular remodeling in MI mice treated with tDCs. Subcutaneously administered infarct lysate-primed tDCs near the inguinal lymph node migrated to the regional lymph node and induced infarct tissue-specific regulatory T-cell populations in the inguinal and mediastinal lymph nodes, spleen, and infarcted myocardium, indicating that a local injection of tDCs induces a systemic activation of MI-specific regulatory T cells. These events elicited an inflammatory-to-reparative macrophage shift. The altered immune environment in the infarcted heart resulted in a better wound remodeling, preserved left ventricular systolic function after myocardial tissue damage, and improved survival.This study showed that tDC therapy in a preclinical model of MI was potentially translatable into an antiremodeling therapy for ischemic tissue repair.
Outcomes Associated With Subcutaneous Implantable Cardioverter Defibrillators
Authors: Abdul Wase, Thein T. Aung, Ronald J. Markert
Journal: JAMA Cardiology (2017)

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 Cardiology 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 Cardiology journal
Acute detachment of hexokinase II from mitochondria modestly increases oxygen consumption of the intact mouse heart
Authors: Rianne Nederlof, Simone Denis, Benjamin Lauzier, Christine Des Rosiers, Markku Laakso, Jacob Hagen, Carmen Argmann, Ronald Wanders, Riekelt H. Houtkooper, Markus W. Hollmann, Sander M. Houten, Coert J. Zuurbier
Journal: Metabolism (2017)
Metabolic Markers and Statistical Prediction of Serous Ovarian Cancer Aggressiveness by Ambient Ionization Mass Spectrometry Imaging
Authors: Marta Sans, Kshipra Gharpure, Robert Tibshirani, Jialing Zhang, Li Liang, Jinsong Liu, Jonathan H. Young, Robert L. Dood, Anil K. Sood, Livia S. Eberlin
Journal: Cancer Research (2017)

Ovarian high-grade serous carcinoma (HGSC) results in the highest mortality among gynecological cancers, developing rapidly and aggressively. Dissimilarly, serous borderline ovarian tumors (BOT) can progress into low-grade serous carcinomas and have relatively indolent clinical behavior. The underlying biological differences between HGSC and BOT call for accurate diagnostic methodologies and tailored treatment options, and identification of molecular markers of aggressiveness could provide valuable biochemical insights and improve disease management. Here, we used desorption electrospray ionization (DESI) mass spectrometry (MS) to image and chemically characterize the metabolic profiles of HGSC, BOT, and normal ovarian tissue samples. DESI-MS imaging enabled clear visualization of fine papillary branches in serous BOT and allowed for characterization of spatial features of tumor heterogeneity such as adjacent necrosis and stroma in HGSC. Predictive markers of cancer aggressiveness were identified, including various free fatty acids, metabolites, and complex lipids such as ceramides, glycerophosphoglycerols, cardiolipins, and glycerophosphocholines. Classification models built from a total of 89,826 individual pixels, acquired in positive and negative ion modes from 78 different tissue samples, enabled diagnosis and prediction of HGSC and all tumor samples in comparison with normal tissues, with overall agreements of 96.4% and 96.2%, respectively. HGSC and BOT discrimination was achieved with an overall accuracy of 93.0%. Interestingly, our classification model allowed identification of three BOT samples presenting unusual histologic features that could be associated with the development of low-grade carcinomas. Our results suggest DESI-MS as a powerful approach for rapid serous ovarian cancer diagnosis based on altered metabolic signatures. Cancer Res; 77(11); 2903-13. ©2017 AACR.
Master Transcriptional Regulators in Cancer: Discovery via Reverse Engineering Approaches and Subsequent Validation
Authors: Bruce Moran, Arman Rahman, Katja Palonen, Fiona T. Lanigan, William M. Gallagher
Journal: Cancer Research (2017)

Reverse engineering of transcriptional networks using gene expression data enables identification of genes that underpin the development and progression of different cancers. Methods to this end have been available for over a decade and, with a critical mass of transcriptomic data in the oncology arena having been reached, they are ever more applicable. Extensive and complex networks can be distilled into a small set of key master transcriptional regulators (MTR), genes that are very highly connected and have been shown to be involved in processes of known importance in disease. Interpreting and validating the results of standardized bioinformatic methods is of crucial importance in determining the inherent value of MTRs. In this review, we briefly describe how MTRs are identified and focus on providing an overview of how MTRs can and have been validated for use in clinical decision making in malignant diseases, along with serving as tractable therapeutic targets. Cancer Res; 77(9); 2186-90. ©2017 AACR.
HLA-Bw4 80(T) and multiple HLA-Bw4 copies combined with KIR3DL1 associate with spontaneous clearance of HCV infection in people who inject drugs
Authors: Christine Thöns, Tina Senff, Theresa J. Hydes, Angela R. Manser, Falko M. Heinemann, Andreas Heinold, Martin Heilmann, Arthur Y. Kim, Markus Uhrberg, Norbert Scherbaum, Georg M. Lauer, Salim I. Khakoo, Jörg Timm
Journal: Journal of Hepatology (2017)