tbuckley/cabot-search huggingface dataset:
Regulation of Sox2 and stemness by nicotine and electronic-cigarettes in non-small cell lung cancer
Authors: Courtney M Schaal, Namrata Bora-Singhal, Durairaj Mohan Kumar, Srikumar P Chellappan
Journal: Molecular Cancer (2018)

Lung cancer is the leading cause of cancer related deaths and its incidence is highly correlated with cigarette smoking. Nicotine, the addictive component of tobacco smoke, cannot initiate tumors, but can promote proliferation, migration, and invasion of cells in vitro and promote tumor growth and metastasis in vivo. This nicotine-mediated tumor promotion is facilitated through the activation of nicotinic acetylcholine receptors (nAChRs), specifically the α7 subunit. More recently, nicotine has been implicated in promoting self-renewal of stem-like side-population cells from lung cancers. This subpopulation of cancer stem-like cells has been implicated in tumor initiation, generation of the heterogeneous tumor population, metastasis, dormancy, and drug resistance. Here we describe the molecular events driving nicotine and e-cigarette extract mediated stimulation of self-renewal of stem-like cells from non-small cell lung cancer. Experiments were conducted using A549 and H1650 non-small cell lung cancer cell lines and human mesenchymal stem cells according to protocols described in this paper. 2 μM nicotine or e-cigarette extracts was used in all relevant experiments. Biochemical analysis using western blotting, transient transfections, RT-PCR and cell biological analysis using double immunofluorescence and confocal microscopy, as well as proximity ligation assays were conducted. Here we demonstrate that nicotine can induce the expression of embryonic stem cell factor Sox2, which is indispensable for self-renewal and maintenance of stem cell properties in non-small cell lung adenocarcinoma (NSCLC) cells. We further demonstrate that this occurs through a nAChR-Yap1-E2F1 signaling axis downstream of Src and Yes kinases. Our data suggests Oct4 may also play a role in this process. Over the past few years, electronic cigarettes (e-cigarettes) have been promoted as healthier alternatives to traditional cigarette smoking as they do not contain tobacco; however, they do still contain nicotine. Hence we have investigated whether e-cigarette extracts can enhance tumor promoting properties similar to nicotine; we find that they can induce expression of Sox2 as well as mesenchymal markers and enhance migration and stemness of NSCLC cells. Our findings shed light on novel molecular mechanisms underlying the pathophysiology of smoking-related lung cancer in the context of cancer stem cell populations, and reveal new pathways involved that could potentially be exploited therapeutically.
<i>NEJM</i>retracts article from former researcher once hailed as heart stem cell pioneer
Authors: Owen Dyer
Journal: BMJ (2018)

The New England Journal of Medicine has retracted one paper1 and issued an “expression of concern” about two others2 within days of Harvard Medical School and Brigham and Women’s Hospital announcing that they had asked various journals to retract 31 papers from a laboratory once hailed for pioneering stem cell research but now discredited by findings of research misconduct.

The articles came from the laboratory of Piero Anversa, who came to prominence when he appeared to produce evidence for his long standing contention that science had underestimated the heart’s capacity for self repair.

In its retraction notice, NEJM said that several of Anversa’s coauthors asked the journal to retract the 2011 study Evidence for human lung stem cells .

The unnamed authors wrote to tell NEJM that a review by Harvard …
A randomized phase II study to assess trastuzumab beyond progression in HER2-positive advanced gastric cancer: WJOG7112G
Authors: Taito Esaki, Hiroshi Tsukuda, Nozomu Machida, Hiroyasu Ishida, Shigenori Kadowaki, Keiko Minashi, Shinya Tokunaga, Yukinori Ozaki, Chihiro Kondoh, Akitaka Makiyama, Yasutaka Sukawa, Takeharu Yamanaka, Kentaro Yamazaki, Shuichi Hironaka, Kei Muro
Journal: Annals of Oncology (2018)
Canadians quit World Medical Association over president’s plagiarised speech
Authors: Owen Dyer
Journal: BMJ (2018)

The Canadian Medical Association (CMA) has left the World Medical Association (WMA), the global body created to promote medical ethics, after the new WMA president used parts of a former CMA president’s speech in his first address as leader.

The Canadians were attending the WMA’s general assembly in Reykjavik when new president Leonid Eidelman addressed the conference. Among the audience was Ontario physician Chris Simpson, who had given his own inaugural address when he became CMA president in 2014.

Simpson told Canada’s Globe and Mail newspaper: “I suddenly heard familiar words, and I turned to one of my colleagues and said ‘This is my speech!’”

Simpson began speaking …
Abstract 17361: Low Dose- High Frequency, Case Based Psychomotor CPR Training Improves Compression Fraction for Patients With In-hospital Cardiac Arrest
Authors: Ashish R Panchal, Gregory Norton, Emily Gibbons, Jeri Buehler, Ruchika Husa, David E Slattery, Michael C Kurz
Journal: Circulation (2016)

Background: High quality CPR is critical for survival from cardiac arrest. Low dose- high frequency case based simulation has been demonstrated to be a feasible method to enhance CPR skill retentio...
Abstract PR11: Synthetic lethality between ATRX mutations and MYCN amplification in neuroblastoma
Authors: Maged Zeineldin, Sara M. Federico, Lyra Griffith, Jongyre Jeon, Xiang Chen, John Easton, Jianrong Wu, Shenghua Mao, Yanling Liu, Arlene Naranjo, Alberto S. Pappo, Michael D. Hogarty, Michael A. Dyer
Journal: Cancer Research (2018)

Abstract Neuroblastoma is a clinically heterogeneous tumor responsible for 15% of cancer-related deaths in children. Older age at diagnosis and MYCN amplification are associated with poor prognosis in neuroblastoma. Previously, sequencing stage 4 neuroblastoma tumors revealed recurrent mutations in the chromatin remodeler ATRX that are significantly associated with older age and mutually exclusive with MYCN amplification. Here, we expanded our genetic analysis of neuroblastoma across all ages and stages. We sequenced 475 neuroblastoma tumors and found that the incidence of ATRX mutations is correlated with older age at diagnosis and advanced stages of the disease. We also directly studied the mutual exclusivity between ATRX mutations and MYCN amplification using both cultured cells and orthotopic mouse models. We found that targeting ATRX using shRNA or CRISPR-Cas-9 reduces cell viability in MYCN-amplified cells. Additionally, induction of MYCN overexpression results in cell death in ATRX-mutant neuroblastoma cells. To characterize the molecular basis of the ATRX-mutations/MYCN-amplification incompatibility, we studied epigenetic, metabolic, and replicative changes associated with MYCN amplification in these cells. We discovered that induction of MYCN overexpression provokes mitochondrial abnormalities, metabolic reprograming, and replicative stress in ATRX mutant cells. Collectively, these data show synthetic lethality between ATRX mutations and MYCN amplification and suggest that the chromatin remodeler ATRX is important in reducing replicative stress associated with MYCN amplification in neuroblastoma. These data will also help in identifying therapeutic targets, which will reduce the morbidity and mortality associated with high-risk neuroblastoma. Citation Format: Maged Zeineldin, Sara M. Federico, Lyra Griffith, Jongyre Jeon, Xiang Chen, John Easton, Jianrong Wu, Shenghua Mao, Yanling Liu, Arlene Naranjo, Alberto S. Pappo, Michael D. Hogarty, Michael A. Dyer. Synthetic lethality between ATRX mutations and MYCN amplification in neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr PR11.
Unrelated donor vs HLA-haploidentical α/β T-cell– and B-cell–depleted HSCT in children with acute leukemia
Authors: Alice Bertaina, Marco Zecca, Barbara Buldini, Nicoletta Sacchi, Mattia Algeri, Francesco Saglio, Cesare Perotti, Anna Maria Gallina, Valentina Bertaina, Edoardo Lanino, Arcangelo Prete, Walter Barberi, Manuela Tumino, Claudio Favre, Simone Cesaro, Francesca Del Bufalo, Mimmo Ripaldi, Stella Boghen, Gabriella Casazza, Marco Rabusin, Adriana Balduzzi, Franca Fagioli, Daria Pagliara, Franco Locatelli
Journal: Blood (2018)
Abstract P228: Milkfat Consumption, Dyslipidemia, and Body Weight in Children
Authors: Ahlia Sekkarie, Janet Figueroa, Caroline Um, Jean Welsh
Journal: Circulation (2018)

Background: Dietary guidelines recommend consumption of 1% or skim (i.e. non-fat) milk for children &gt;2 years due to concerns about the role of saturated fat in raising low-density lipoprotein cholesterol (LDL) levels and cardiovascular disease risk. Low- or non-fat milk is also recommended to promote energy balance and reduce obesity risk. While more recent evidence in adults suggests no association between milkfat and cardiovascular disease risk, this association has not been well studied among children who tend to be the highest consumers of milk. No known studies have demonstrated an association between milkfat consumption and lipid levels in children. Our objective was to determine if there is an association between milk fat consumption and risk of dyslipidemia and obesity among U.S. children. Methods: We used cross-sectional data from children 2-19 years from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 (n=7261). Usual milkfat intake (i.e. never/rare milk consumption, non-fat, 1%, 2%, or whole) was self-reported by parent or child. Lipid levels (12-19 years only) and adiposity (BMI z-score and weight category [underweight, normal, overweight, or obese] in all ages) were assessed by trained staff using standardized methods. Covariates included child age, sex, household income, race/ethnicity, physical activity, dieting, and total energy intake. We used multivariate linear and logistic regression models to examine the association between milkfat consumption and our outcomes and conducted pairwise comparisons to assess differences between different milkfat consumers. Results: Most children consumed 2% milk (42.3%), followed by whole (26.1%), 1% milk (11.7%), never/rare consumption (10.2%), and nonfat (9.7%). We found no significant trends in mean cholesterol (total, HDL, LDL) with consumption of milk with greater fat content. There was a significant trend towards higher triglycerides as milkfat intake increased (p=0.01) though this association was stronger among 2% milk compared to whole fat consumers. We found no significant trend in prevalence of each BMI category across milk fat intake. Pairwise comparisons demonstrated that usual consumption of 1% and 2% milkfat was associated with both higher BMI Z-score and odds of obesity compared to whole milk. Conclusion: We found no significant linear trend between usual %milk fat consumed and indicators of cardiovascular disease (BMI-Z and lipid levels) in children, except for triglycerides which rose as milkfat intake increased. However, triglycerides were higher among the 2% compared to whole milkfat consumers. Overall, whole milk was not associated with increased indicators of cardiovascular disease risk in children.
Risk Factors for Rate of Relapse and Effects of Steroid Maintenance Therapy in Patients With Autoimmune Pancreatitis: Systematic Review and Meta-analysis
Authors: Matteo Tacelli, Ciro Celsa, Bianca Magro, Luca Barresi, Salvatore Guastella, Gabriele Capurso, Luca Frulloni, Giuseppe Cabibbo, Calogero Cammà
Journal: Clinical Gastroenterology and Hepatology (2018)
Abstract 19055: Myocardial Deformation Analysis Reveals Early Cardiac Abnormalities in Patients With Hutchinson Gilford Progeria Syndrome
Authors: Fatima I Lunze, Tor Biering-Sørensen, Sheila M Hegde, Steven D Colan, Leslie Smoot, Leslie Gordon, Monica Kleinman, Mark Kieran, Ashwin Prakash
Journal: Circulation (2016)

Background: Patients with Hutchinson-Gilford Progeria Syndrome (HGPS) demonstrate accelerated aging with premature cardiovascular morbidity and mortality. While left ventricular ejection fraction (...
T-Cell-Intrinsic Receptor Interacting Protein 2 Regulates Pathogenic T Helper 17 Cell Differentiation
Authors: Kenichi Shimada, Rebecca A. Porritt, Janet L. Markman, Jacqueline Gire O’Rourke, Daiko Wakita, Magali Noval Rivas, Chihiro Ogawa, Lina Kozhaya, Gislâine A. Martins, Derya Unutmaz, Robert H. Baloh, Timothy R. Crother, Shuang Chen, Moshe Arditi
Journal: Immunity (2018)
Oncological outcome of fat grafting for breast reconstruction after cancer
Authors: G. Griguolo, F. Miglietta, M.V. Dieci, V. Vindigni, F. Bassetto, E. De Antoni, I. Polico, A. Marchet, E. Baldan, G. Vernaci, T. Saibene, S. Michieletto, V. Guarneri
Journal: Annals of Oncology (2018)
Efficacy and safety of nivolumab in patients with uterine cervical cancer, uterine corpus cancer, or soft-tissue sarcoma
Authors: Noriyuki Katsumata, Kenji Tamura, Kosei Hasegawa, Koji Matsumoto, Hirofumi Mukai, Shunji Takahashi, Hiroyuki Nomura, Hironobu Minami
Journal: Annals of Oncology (2018)
HIF-1α Upregulation in TP53 Disrupted Chronic Lymphocytic Leukemia Cells and Its Potential Role As a Therapeutic Target
Authors: Valentina Griggio, Candida Vitale, Maria Todaro, Chiara Riganti, Joanna Kopecka, Michele Dal Bo, Davide Rossi, Gabriele Pozzato, Monia Marchetti, Marina Ruggeri, Paola Omedè, Luca Laurenti, Giovanni Del Poeta, Francesca Romana Mauro, Valter Gattei, Gianluca Gaidano, Robin Foa, Massimo Massaia, Mario Boccadoro, Marta Coscia
Journal: Blood (2016)
Elastography Can Map the Local Inverse Relationship between Shear Modulus and Drug Delivery within the Pancreatic Ductal Adenocarcinoma Microenvironment
Authors: Hexuan Wang, Reem Mislati, Rifat Ahmed, Phuong Vincent, Solumtochukwu F. Nwabunwanne, Jason R. Gunn, Brian W. Pogue, Marvin M. Doyley
Journal: Clinical Cancer Research (2018)

High tissue pressure prevents chemotherapeutics from reaching the core of pancreatic tumors. Therefore, targeted therapies have been developed to reduce this pressure. While point probes have shown the effectiveness of these pressure-reducing therapies via single-location estimates, ultrasound elastography is now widely available as an imaging technique to provide real-time spatial maps of shear modulus (tissue stiffness). However, the relationship between shear modulus and the underlying tumor microenvironmental causes of high tissue pressure has not been investigated. In this work, elastography was used to investigate how shear modulus influences drug delivery in situ, and how it correlates with collagen density, hyaluronic acid content, and patent vessel density-features of the tumor microenvironment known to influence tissue pressure.Intravenous injection of verteporfin, an approved human fluorescent drug, was used in two pancreatic cancer xenograft models [AsPC-1 (n = 25) and BxPC-3 (n = 25)].Fluorescence intensity was higher in AsPC-1 tumors than in BxPC-3 tumors (P < 0.0001). Comparing drug uptake images and shear wave elastographic images with histologic images revealed that: (i) drug delivery and shear modulus were inversely related, (ii) shear modulus increased linearly with increasing collagen density, and (iii) shear modulus was marginally correlated with the local assessment of hyaluronic acid content.These results demonstrate that elastography could guide targeted therapy and/or identify patients with highly elevated tissue pressure.See related commentary by Nia et al., p. 2024.
CRISPR-induced exon skipping is dependent on premature termination codon mutations
Authors: Tingting Sui, Yuning Song, Zhiquan Liu, Mao Chen, Jichao Deng, Yuanyuan Xu, Liangxue Lai, Zhanjun Li
Journal: Genome biology (2018)

In previous studies, CRISPR/Cas9 was shown to induce unexpected exon skipping; however, the mechanism by which this phenomenon is triggered is controversial. By analyzing 22 gene-edited rabbit lines generated using CRISPR/Cas9, we provide evidence of exon skipping at high frequency in premature termination codon-mutated rabbits but not in the rabbits with a premature termination codon mutation in exon 1 rabbits with non-frameshift or missense mutations. Our results suggest that CRISPR-mediated exon skipping depends on premature termination codon mutation-induced nonsense-associated altered splicing.
GW29-e1504 Chronic restraint stress impairs ischemia-induced neovascularization through DPP-4-dependent pathway
Authors: Juntao Fang, Liyuan Zhu, Shangyu Liu, Sheng Hu, Huifeng Hao, Siyuan Wang, Kaihao Wang, Miao Wang, Yida Tang, Ping Li
Journal: Journal of the American College of Cardiology (2018)
Double blind concordance study of colo-rectal cancer treatment recommendations between artificial intelligence advisory programme watson for oncology (WFO) &amp; multidisciplinary tumor board (MDT)
Authors: S. Sampige Prasannakumar, M. Sepulveda, C. Rohit Kumar, A. Rauthan, P. Patil, Y. Ramya
Journal: Annals of Oncology (2018)
GW29-e1318 Coupling Interval Variability Discriminate Idiopathic Outflow Tract Premature Ventricular Contractions Arising in Aortic Sinus Cusp from Right Ventricular Outflow Tract
Authors: Fen Qin, Yuwei Zhao, Fan Bai, Na Liu, Yingxu Ma, Biao Li, Chao Sun, Yixi Li, Hailong Tao, Jianzeng Dong, Deyong Long, Qiming Liu
Journal: Journal of the American College of Cardiology (2018)
Process evaluation and the development of behavioural interventions to improve psychological distress among survivors of critical illness
Authors: Ann M. Parker, Albahi Malik, Megan Hosey
Journal: Thorax (2018)

Depressive, anxiety and post-traumatic stress disorder (PTSD) symptoms are common, long-lasting and associated with worse quality of life among intensive care unit (ICU) survivors.1–4 There are few clinical trials evaluating interventions to improve these symptoms. Cox and colleagues evaluated the feasibility of a mobile mindfulness training application (App) to address psychological stress after critical illness.5 Mindfulness promotes non-judgmental awareness of the present and acceptance of emotions, thoughts (eg, ‘I’m broken’, ‘I’m dependent’) and physiological states (eg, pain, shortness of breath), thus improving engagement with thoughts and behaviours related to illness along with coping and medical management of disease.6 

This multisite pilot randomised controlled trial (RCT) randomised 80 participants to one of the three groups: mobile App, telephone mindfulness training or education control. Eligibility criteria included adults in the ICU ≥24 hours with cardiorespiratory failure. Participants randomised to mobile mindfulness intervention interacted with the App over 4 weekly mindfulness training sessions. Participants in the telephone group completed 4 weekly telephone mindfulness sessions (~30 min each) with a trained psychologist. The education control group received two telephone calls and a self-directed web-based programme focused on the nature and treatment of critical illness. Primary outcomes included feasibility, acceptability and usability. Secondary outcomes included depressive, anxiety and PTSD symptoms.

Approximately 83% (n=66) of patients completed the study. Loss to follow-up was 29%, 10% and 11% in the mobile mindfulness, telephone mindfulness and education groups, respectively. The percentage of participants who were not lost to follow-up completing all intervention sessions was ≥92% in each group. The results demonstrated ‘strong’ acceptability and usability with qualitative feedback considered overall ‘positive’ regarding the App. At 3-month follow-up, preliminary data demonstrated no significant improvement from baseline (before hospital discharge) in anxiety and depressive symptoms in the education control group while there was a trend toward improvements in these symptoms in the mobile and …
Lipidic prodrug approach for improved oral drug delivery and therapy
Authors: Milica Markovic, Shimon Ben‐Shabat, Shahar Keinan, Aaron Aponick, Ellen M. Zimmermann, Arik Dahan
Journal: Medicinal Research Reviews (2018)

Abstract In the past, a prodrug design was used as a last option to improve bioavailability through controlling transport, distribution, metabolism, or other mechanisms. Prodrugs are currently used even in early stages of drug development, and a significant percentage of all drugs in the market are prodrugs. The focus of this article is lipidic prodrugs, a strategy whereby a lipid carrier is covalently bound to the drug moiety. The increased lipophilicity of the lipid‐drug conjugate can improve the pharmacokinetic profile and provide meaningful advantages: increased absorption across biological barriers, prolonged circulation half‐life, selective distribution profile (eg brain penetration), reduced hepatic first‐pass metabolism, and overall enhanced bioavailability of the parent drug. Moreover, lipidic prodrugs may join the endogenous lipid trafficking pathways, thereby facilitate drug targeting, either by selective absorption pathway (eg lymphatic transport) or drug release at specific target site(s). The different lipid‐drug conjugates (triglyceride‐, fatty acids, phospholipid‐, and steroid‐based prodrugs), the physiological barriers that challenge the absorption of these conjugates, followed by their current utilization and potential clinical benefits are described and analyzed, and future opportunities this approach could provide are discussed. Altogether, lipidic prodrugs represent an exciting approach for improving different aspects of oral drug delivery/therapy and may provide solutions for various unmet needs; the use of this strategy is expected to grow.
P3.09-10 Circulating Cell-Free DNA (cfDNA) Molecular Profile of Thai NSCLC Patients Using Difference Variant Frequency of NGS
Authors: N. Iemwimangsa, N. Trachu, V. Pairoj, A. Charoenyingwattana, P. Incharoen, S. Detarkom, S. Lukrak, L. Arsa, N. Monnamo, S. Techasurungkul, T. Reungwetwattana, W. Chantratita
Journal: Journal of Thoracic Oncology (2018)
Esophageal Lichen Planus Is Associated With a Significant Increase in Risk of Squamous Cell Carcinoma
Authors: Karthik Ravi, D. Chamil Codipilly, Dharma Sunjaya, Hongfei Fang, Amindra S. Arora, David A. Katzka
Journal: Clinical Gastroenterology and Hepatology (2018)
Association Between Endoscopist Personality and Rate of Adenoma Detection
Authors: Ghideon Ezaz, Daniel A. Leffler, Scott Beach, Robert E. Schoen, Seth D. Crockett, Rebecca A. Gourevitch, Sherri Rose, Michele Morris, David S. Carrell, Julia B. Greer, Ateev Mehrotra
Journal: Clinical Gastroenterology and Hepatology (2018)
P3.15-24 Ramathibodi Lung Cancer Consortium (RLC) Model: Multidisciplinary Team Approach Improves Lung Cancer Patients’ Survival Outcome
Authors: T. Reungwetwattana, T. Suwattanapongched, W. Sukkasem, C. Nitiwarangkul, P. Incharoen, M. Ngodngamthaweesuk, P. Leelayana, P. Cherntanomwong, S. Khajarern, T. Ativitavas, P. Chansriwong, E. Sirachainan, A. Kositwattanarerk, W. Chamroonrat, R. Ruaungkanchanasetr, P. Puataweepong, T. Swangsilpa, S. Dangprasert, N. Aulmongkon, B. Wetchaphan, N. Darayen, V. Tangsujaritvijit
Journal: Journal of Thoracic Oncology (2018)