tbuckley/cabot-search huggingface dataset:
Claudin-18: unexpected regulator of lung alveolar epithelial cell proliferation
Authors: Darrell N. Kotton
Journal: Journal of Clinical Investigation (2018)

Claudin 18 (CLDN18) is a tight junction protein that is highly expressed in the lung. While mice lacking CLDN18 exhibit the expected loss of epithelial integrity in the lung, these animals also have unexpectedly large lungs. In this issue of the JCI, Zhou, Flodby, and colleagues reveal that the increased lung size of Cldn18-/- mice is the result of increased type 2 alveolar epithelial (AT2) cell proliferation. This increase in proliferation was shown to be driven by translocation of the transcriptional regulator Yes-associated protein (YAP) to the nucleus and subsequent induction of proliferative pathways. CLDN18-deficent mice also had increased frequency of lung adenocarcinomas. Together, the results of this study advance our understanding of the mechanisms that likely regulate homeostasis of the normal lung as well as promote the proliferative state of malignant cells found in lung adenocarcinomas thought to originate from AT2 cells.
Meningococcal disease and control in China: Findings and updates from the Global Meningococcal Initiative (GMI)
Authors: Junhong Li, Zhujun Shao, Gang Liu, Xilian Bai, Ray Borrow, Min Chen, Qinglan Guo, Yue Han, Yixing Li, Muhamed-Kheir Taha, Xihai Xu, Xin Xu, Huizhen Zheng
Journal: Journal of Infection (2018)
Reference percentiles of FEV1 for the Canadian cystic fibrosis population: comparisons across time and countries
Authors: Sang-Ook Kim, Mary Corey, Anne L Stephenson, Lisa J Strug
Journal: Thorax (2018)

Background Forced expiratory volume in 1 s (FEV1) indicates lung health in cystic fibrosis (CF). FEV1 is commonly communicated as a per cent predicted of a healthy individual sharing the same age, sex, race and height. CF-specific reference equations are complementary and calibrate a patient’s FEV1 to that of their CF peers. Objectives (1) To derive Canadian CF-specific FEV1 reference percentiles (FEV1%iles), (2) characterize how they have changed over time and (3) compare the Canadian FEV1%iles to those for USA and European CF populations. Method CF FEV1%iles are calculated using the Canadian CF Registry and quantile regression. Results The Canadian FEV1%iles demonstrated better lung function in more recent time periods within Canada, especially below the 50% percentile and in males. When compared to USA and European FEV1%iles for the same time period, Canadian FEV1%iles were higher. Conclusion CF-specific FEV1%iles can provide useful information about changes in lung health. An online calculator (available at cfpercentile.research.sickkids.ca ) makes these FEV1%iles accessible.
ARDS Decreases Pulmonary Artery Compliance in a Porcine Model
Authors: Arnoldo Santos, I Monge-Garcia, E Gomez Peñalver, João Batista Borges, L Lucchetta, Jaime Retamal, G Tusman, Göran Hedenstierna, Anders Larsson, Fernando Suarez-Sipmann
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Importance of pulmonary hemodynamic disarrangements in ARDS has been remarked recently. In this study we describe the effect of ARDS on pulmonary artery compliance and the related effect ...
Clinical Outcome of Prostate Cancer Patients with Germline DNA Repair Mutations: Retrospective Analysis from an International Study
Authors: Joaquin Mateo, Heather H. Cheng, Himisha Beltran, David Dolling, Wen Xu, Colin C. Pritchard, Helen Mossop, Pasquale Rescigno, Raquel Perez-Lopez, Verena Sailer, Michael Kolinsky, Ada Balasopoulou, Claudia Bertan, David M. Nanus, Scott T. Tagawa, Heather Thorne, Bruce Montgomery, Suzanne Carreira, Shahneen Sandhu, Mark A. Rubin, Peter S. Nelson, Johann S. de Bono
Journal: European Urology (2018)

Germline DNA damage repair gene mutation (gDDRm) is found in >10% of metastatic prostate cancer (mPC). Their prognostic and predictive impact relating to standard therapies is unclear. To determine whether gDDRm status impacts benefit from established therapies in mPC. This is a retrospective, international, observational study. Medical records were reviewed for 390 mPC patients with known gDDRm status. All 372 patients from Royal Marsden (UK), Weill-Cornell (NY), and University of Washington (WA) were previously included in a prevalence study (Pritchard, NEJM 2016); the remaining 18 were gBRCA1/2m carriers, from the kConFab consortium, Australia. Response rate (RR), progression-free survival (PFS), and overall survival (OS) data were collected. To account for potential differences between cohorts, a mixed-effect model (Weibull distribution) with random intercept per cohort was used. The gDDRm status was known for all 390 patients (60 carriers of gDDRm [gDDRm+], including 37 gBRCA2m, and 330 cases not found to carry gDDRm [gDDRm–]); 74% and 69% were treated with docetaxel and abiraterone/enzalutamide, respectively, and 36% received PARP inhibitors (PARPi) and/or platinum. Median OS from castration resistance was similar among groups (3.2 vs 3.0 yr, p = 0.73). Median docetaxel PFS for gDDRm+ (6.8 mo) was not significantly different from that for gDDRm– (5.1 mo), and RRs were similar (gDDRm+ = 61%; gDDRm– = 54%). There were no significant differences in median PFS and RR on first-line abiraterone/enzalutamide (gDDRm+ = 8.3 mo, gDDRm– = 8.3 mo; gDDRm+ = 46%, gDDRm– = 56%). Interaction test for PARPi/platinum and gDDRm+ resulted in an OS adjusted hazard ratio of 0.59 (95% confidence interval 0.28–1.25; p = 0.17). Results are limited by the retrospective nature of the analysis. mPC patients with gDDRm appeared to benefit from standard therapies similarly to the overall population; prospective studies are ongoing to investigate the impact of PARPi/platinum. Patients with inherited DNA repair mutations benefit from standard therapies similarly to other metastatic prostate cancer patients.
Feature-Tracking Global Longitudinal Strain Predicts Death in a Multicenter Population of Patients With Ischemic and Nonischemic Dilated Cardiomyopathy Incremental to Ejection Fraction and Late Gadolinium Enhancement
Authors: Simone Romano, Robert M Judd, Raymond J Kim, Han W Kim, Igor Klem, John F Heitner, Dipan J Shah, Jennifer Jue, Brent E White, Raksha Indorkar, Chetan Shenoy, Afshin Farzaneh-Far
Journal: JACC. Cardiovascular imaging (2018)
Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease
Authors: Lawrence S. Honig, Bruno Vellas, Michael Woodward, Mercè Boada, Roger Bullock, Michael Borrie, Klaus Hager, Niels Andreasen, Elio Scarpini, Hong Liu-Seifert, Michael Case, Robert A. Dean, Ann Hake, Karen Sundell, Vicki Poole Hoffmann, Christopher Carlson, Rashna Khanna, Mark Mintun, Ronald DeMattos, Katherine J. Selzler, Eric Siemers
Journal: New England Journal of Medicine (2018)

Alzheimer's disease is characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. The humanized monoclonal antibody solanezumab was designed to increase the clearance from the brain of soluble Aβ, peptides that may lead to toxic effects in the synapses and precede the deposition of fibrillary amyloid.
CBX7 regulates stem cell-like properties of gastric cancer cells via p16 and AKT-NF-κB-miR-21 pathways
Authors: Su-Jie Ni, Li-Qin Zhao, Xiao-Feng Wang, Zhen-Hua Wu, Rui-Xi Hua, Chun-Hua Wan, Jie-Yun Zhang, Xiao-Wei Zhang, Ming-Zhu Huang, Lu Gan, Hua-Lin Sun, Goberdhan P. Dimri, Wei-Jian Guo
Journal: Journal of Hematology & Oncology (2018)

Chromobox protein homolog 7 (CBX7), a member of the polycomb group (PcG) family of proteins, is involved in the regulation of cell proliferation and cancer progression. PcG family members, such as BMI, Mel-18, and EZH2, are integral constituents of the polycomb repressive complexes (PRCs) and have been known to regulate cancer stem cell (CSC) phenotype. However, the role of other PRCs' constituents such as CBX7 in the regulation of CSC phenotype remains largely elusive. This study was to investigate the role of CBX7 in regulating stem cell-like properties of gastric cancer and the underlying mechanisms.Firstly, the role of CBX7 in regulating stem cell-like properties of gastric cancer was investigated using sphere formation, Western blot, and xenograft tumor assays. Next, RNA interference and ectopic CBX7 expression were employed to determine the impact of CBX7 on the expression of CSC marker proteins and CSC characteristics. The expression of CBX7, its downstream targets, and stem cell markers were analyzed in gastric stem cell spheres, common cancer cells, and gastric cancer tissues. Finally, the pathways by which CBX7 regulates stem cell-like properties of gastric cancer were explored.We found that CBX7, a constituent of the polycomb repressive complex 1 (PRC1), plays an important role in maintaining stem cell-like characteristics of gastric cancer cells via the activation of AKT pathway and the downregulation of p16. Spearman rank correlation analysis showed positive correlations among the expression of CBX7 and phospho-AKT (pAKT), stem cell markers OCT-4, and CD133 in gastric cancer tissues. In addition, CBX7 was found to upregulate microRNA-21 (miR-21) via the activation of AKT-NF-κB pathway, and miR-21 contributes to CBX7-mediated CSC characteristics.CBX7 positively regulates stem cell-like characteristics of gastric cancer cells by inhibiting p16 and activating AKT-NF-κB-miR-21 pathway.
Abstract 21261: Circulating Extracellular Vesicles From Mouse and Rat Models of Diabetes Reveal Specific Microrna Signatures as Biomarkers of Diabetic Cardiomyopathy
Authors: Mark Chandy, Makon-Sébastien Njock, Shawn Veitch, Antoinette Bugyei-Twum, Henry Cheng, Abdul Momen, Kim Connelly, Jason Fish, Mansoor Husain
Journal: Circulation (2017)

Background: Type-2 diabetes (T2D) is associated with both reduced and preserved ejection fraction heart failure. Obese db/db mice and Goto Kakizaki (GK) rats represents animals models of T2D that develop cardiac dysfunction similar to human diabetic cardiomyopathy, in which dominant early findings are of diastolic (and not systolic) dysfunction. Circulating extracellular vesicles (EV) contain microRNAs (miR) that can be transferred to recipient cells to modulate their function. We explored whether analysis of EV content from animals models of T2D would inform on the pathophysiology, diagnosis and therapeutic targets of cardiac dysfunction. Hypothesis: EV from animal models of T2D will have altered miR content that contributes to the pathophysiology of diabetic cardiomyopathy. Methods &amp; Results: miR qPCR arrays on circulating EV isolated from plasma of db/db mice reveal several miR (-7, -15, -25, -30e, -148a, -150, -195) modulated during disease progression. These changes in miR content occur prior to echocardiographic evidence of diastolic dysfunction, including global longitudinal strain and strain rate. Among circulating EV miR from the GK rat model, miR-30 was also upregulated (1.42 fold, p=0.03) compared to Wistar rat. In GK rat left ventricle, and in H9C2 rat cardiac myoblast cultured in 25 mM high glucose media, mass spectrometry revealed proteins that were overexpressed in the diabetic heart including oxidative phosphorylation, glycolysis, fatty acid degredation and the citrate cycle. Using a bioinformatics approach, we next identified metabolic pathways affected by miR-30. Based on these findings, in vivo therapy with antagomiR and mimics of miR-30 are underway to test causality and reversibility of the observed cardiomyopathy. Conclusion: EV from animal models of T2D have altered miR content, including miR-30. We also identify alterations in the expression of a network of metabolism genes in the heart, which are implicated in diabetic cardiomyopathy. If causality is supported by experiments that enhance or block miR-30 expression in these models of disease, we will have identified a novel biomarker and therapeutic target for diabetic cardiomyopathy.
Abstract 14743: Intracellular Adenosine Suppresses Vsmc Phenotypic Switch Through Klf4 Gene Methylation
Authors: Yong Wang, Yiming Xu, Xianqiu Zeng, Yaqi Zhou, Zhiping Liu, Chaodong Wu, Qinkai Li, Yuqing Huo
Journal: Circulation (2015)

Background and objective: It is well known that adenosine affects the growth of vascular smooth muscle cells via adenosine receptors. Adenosine kinase (ADK) is an intracellular enzyme regulating the levels of adenosine in intracellular and further extracellular compartments. The effect of ADK on VSMC phenotypic switch is unknown. In this study, we evaluate phenotypic changes of VSCMs both in vitro and in vivo following deletion of ADK in VSMCs. Methods and results: The expression of ADK in vascular wall was significant upregulated in mouse carotid artery ligation model. Heterogeneous deletion of ADK or specific ADK deletion in VSMCs led to remarkably decreased neointima in ligated mouse carotid arteries (Fig. A&amp;B). This was accompanied with increased expression of VSMC differentiation markers and transcriptional factor KLF4 (Fig. D). In an in vitro setup, treatment of VSMCs with ADK shRNA or ADK inhibitors suppressed serum or PDGF-induced SMC proliferation and migration (Fig. C). This effect remained intact in the presence of adenosine receptor antagonists to A1, A2A, A2B and A3. Deletion of ADK in VSMCs increased the levels of intracellular adenosine, decreased the methylation levels of genes and histones, and augmented KLF4 expression. It is being investigated that upregulation of KLF4 was resulted from its gene hypomethylation in response to elevated intracellular adenosine following ADK deletion/knockdown or inhibition. Conclusions: Our data demonstrate that ADK deletion/inhibition suppresses neointima formation in injured arteries through a novel epigenetic pathway but not classic adenosine receptors, and ADK is a promising therapeutic target in the treatment of arterial diseases such as atherosclerosis and arterial neointima formation following arterial angioplasty.
Drug-induced modulation of gp130 signalling prevents articular cartilage degeneration and promotes repair
Authors: Ruzanna Shkhyan, Ben Van Handel, Jacob Bogdanov, Siyoung Lee, Yifan Yu, Mila Scheinberg, Nicholas W Banks, Sean Limfat, Arthur Chernostrik, Carlos Eduardo Franciozi, Mohammad Parvez Alam, Varghese John, Ling Wu, Gabriel B Ferguson, Ali Nsair, Frank A Petrigliano, C Thomas Vangsness, Kanagasabai Vadivel, Paul Bajaj, Liming Wang, Nancy Q Liu, Denis Evseenko
Journal: Annals of the Rheumatic Diseases (2018)

Objective Human adult articular cartilage (AC) has little capacity for repair, and joint surface injuries often result in osteoarthritis (OA), characterised by loss of matrix, hypertrophy and chondrocyte apoptosis. Inflammation mediated by interleukin (IL)-6 family cytokines has been identified as a critical driver of proarthritic changes in mouse and human joints, resulting in a feed-forward process driving expression of matrix degrading enzymes and IL-6 itself. Here we show that signalling through glycoprotein 130 (gp130), the common receptor for IL-6 family cytokines, can have both context-specific and cytokine-specific effects on articular chondrocytes and that a small molecule gp130 modulator can bias signalling towards anti-inflammatory and antidegenerative outputs. Methods High throughput screening of 170 000 compounds identified a small molecule gp130 modulator termed regulator of cartilage growth and differentiation (RCGD 423) that promotes atypical homodimeric signalling in the absence of cytokine ligands, driving transient increases in MYC and pSTAT3 while suppressing oncostatin M- and IL-6-mediated activation of ERK and NF-κB via direct competition for gp130 occupancy. Results This small molecule increased proliferation while reducing apoptosis and hypertrophic responses in adult chondrocytes in vitro. In a rat partial meniscectomy model, RCGD 423 greatly reduced chondrocyte hypertrophy, loss and degeneration while increasing chondrocyte proliferation beyond that observed in response to injury. Moreover, RCGD 423 improved cartilage healing in a rat full-thickness osteochondral defect model, increasing proliferation of mesenchymal cells in the defect and also inhibiting breakdown of cartilage matrix in de novo generated cartilage. Conclusion These results identify a novel strategy for AC remediation via small molecule-mediated modulation of gp130 signalling.
Assessing Metronomic Chemotherapy for Progressive Pediatric Solid Malignant Tumors—Reply
Authors: Raja Pramanik, Sreenivas Vishnubhatla, Sameer Bakhshi
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia
Authors: Jae H Park, Isabelle Rivière, Mithat Gonen, Xiuyan Wang, Brigitte Sénéchal, Kevin J Curran, Craig Sauter, Yongzeng Wang, Bianca Santomasso, Elena Mead, Mikhail Roshal, Peter Maslak, Marco Davila, Renier J Brentjens, Michel Sadelain
Journal: New England Journal of Medicine (2018)

CD19-specific chimeric antigen receptor (CAR) T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL) and long-term remissions in a subgroup of patients.
Dual PD1/LAG3 immune checkpoint blockade limits tumor development in a murine model of chronic lymphocytic leukemia
Authors: Marina Wierz, Sandrine Pierson, Léa Guyonnet, Elodie Viry, Audrey Lequeux, Anaïs Oudin, Simone P. Niclou, Markus Ollert, Guy Berchem, Bassam Janji, Coralie Guérin, Jerome Paggetti, Etienne Moussay
Journal: Blood (2018)
Abstract 20161: Second-generation versus First-generation Drug-eluting Stents in Coronary Long Lesions: Pooled Analysis of The GRAND-DES Registry
Authors: Min Gyu Kong, Jung-Kyu Han, Han-Mo Yang, Kyung Woo Park, Hyun-Jae Kang, Bon-Kwon Koo, Hyo-Soo Kim
Journal: Circulation (2017)

Backgrounds: Coronary long lesion is one of important predictors for a worse outcome after PCI. New DESs generally demonstrated better outcomes than First-generation DESs in a large of proven studi...
Abstract 11439: A Role of Esophageal Cancer Related Gene-4 for Atrial Fibrillation
Authors: Hua Yu, Li Huang, Xinrong Fan, Jun Cheng, Pengyun Li, Xuehui Fan, Xiaorong Zeng, Xitong Dang
Journal: Circulation (2016)

Introduction: Epidemiological studies have shown that the incidence of atrial fibrillation(AF), the most common type of arrthymia, is more than doubled in cancer patients than that in general population, and reciprocally that the incidence of tumor is ten times higher in AF patients than in non-AF patients. However, the molecular link between tumor and AF remain obscure. Esophageal Cancer Related Gene-4 (Ecrg4), a newly-discovered tumor suppressor gene that is highly expressed in atria and conduction systems of heart, has been shown to function as a ‘sentinel’ molecule in tissue homeostasis, meaning that the presence of Ecrg4 calls for no actions, whereas the loss of Ecrg4 upon injury causes the activation of pro-inflammatory cascade and proliferative responses including fibrosis. Hypothesis: Since injury-induced loss of Ecrg4 in tumor leads to systemic inflammation and increased fibrosis that are well-known inducing factors to AF, we hypothesize that Ecrg4 in heart plays a critical role in the pathogenesis of AF. Methods: The expression of Ecrg4 was evaluated by IHC, IF, and RT-PCR. Canine AF model was established by rapid right atrial pacing at 600 beats/min. for 6 hours. Results: The expression of Ecrg4 was higher in atria and conduction systems than that in ventricles of rat heart by IHC, which was confirmed by RT-PCR. In neonatal rat cardiomyocytes, the expression of Ecrg4, localized in perinucler region and in the ER, is higher in atria than in ventricles. Knock-down Ecrg4 expression by siRNA in atrial cardiomyocytes significantly shortened the duration of action potential. Moreover, in a canine AF model, the expression of Ecrg4 in both Sinus node and left atria was significantly down-regulated compared to that in control animals. Conclusions: Expression of Ecrg4 is high in atria and heart conduction systems and down-regulated in AF, suggesting that Ecrg4 may play a critical role in the pathogenesis of AF.
Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations
Authors: J. Mogensen
Journal: Journal of Clinical Investigation (2003)

Mutation analysis of TNNI3 by direct sequencing identified a 87A→G nucleotide substitution of exon 8 resulting in an Asp190Gly amino acid substitution that segregated with the disease in the family (maximal two-point lode score: 4.8).Direct sequencing of TNNI3 identified a 93G→A nucleotide substitution of exon 8, which resulted in an Arg192His amino acid substitution.
GMC erasure: it could have been me
Authors: Susan Bewley
Journal: BMJ (2018)

The details and legal analysis around the death of Jack Adcock—a 6 year old with Down’s syndrome whose life was not saved from overwhelming sepsis—are harrowing.1 Pity all the actors in this tragedy. Compassion demands that we understand his family’s grief and the General Medical Council’s desire to pursue a doctor who has already been convicted of manslaughter and in the court of public opinion. 

No one comes to work with the intention of failing in their duty of …
Whole-exome sequencing reveals differences between nail apparatus melanoma and acral melanoma
Authors: Minho Lee, Jonghwan Yoon, Yeun-Jun Chung, Soo Young Lee, Jin Young Choi, Ok Ran Shin, Ho Youn Park, Won-Jong Bahk, Dong Soo Yu, Young Bok Lee
Journal: Journal of the American Academy of Dermatology (2018)
Aetiology of lower respiratory tract infection in adults in primary care: a prospective study in 11 European countries
Authors: M. Ieven, S. Coenen, K. Loens, C. Lammens, F. Coenjaerts, A. Vanderstraeten, B. Henriques-Normark, D. Crook, K. Huygen, C.C. Butler, T.J.M. Verheij, P. Little, K. Zlateva, A. van Loon, E.C.J. Claas, H. Goossens
Journal: Clinical Microbiology and Infection (2018)