tbuckley/cabot-search huggingface dataset:
Involvement of Sirt1 in ultraviolet radiation mediated damages and transformation of skin keratinocytes
Authors: Shannon Reagan-Shaw, Brittney Jung, Nihal Ahmad
Journal: Cancer Research (2008)

4826  Ultraviolet (UV) radiation is a well-established causative factor for non-melanoma skin cancers, precancerous conditions such as actinic keratoses and skin aging. Further, like several other cancers, skin cancer is believed to be associated with aging. Therefore, it may be useful to decipher the molecular determinant(s) that connect skin aging and skin cancer. Sirtuins are nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylases which have been implicated in the process of aging. Studies are increasingly suggesting that Sirtuins may be involved in cancer development. Sirt1 is the most well studied member of sirtuin family that has been shown to be linked to cell longevity through a number of biological functions such as gene silencing, apoptosis, fatty acid metabolism, oxidative stress and regulation of cellular life span. In this study, we tested the hypothesis that Sirt1 plays a critical role in the UV response including UV-induced transformation of skin keratinocytes. To test this hypothesis, we examined the effect of UVA (0.1 to 0.4 J/cm2) and UVB (10 to 200 mJ/cm2), alone or in combination, on Sirt1 in normal human epidermal keratinocytes (NHEK), hTERT immortalized keratinocytes (N/TERT-1) and HaCaT immortalized keratinocytes. Studies have shown that repeated UVA and UVB exposures leads to a transformed phenotype in HaCaT keratinocytes. Single UVA or UVB treatment to NHEK cells resulted in an initial increase followed by a decrease in Sirt1 protein levels. Interestingly, single UVA or UVB treatment to N/TERT-1 or HaCaT cells resulted in a dose-dependent decrease in Sirt1 protein levels as well as Sirt1 activity. Further, repeated exposures to N/TERT-1 and HaCaT keratinocytes with a combination of UVA and UVB resulted in an initial decrease in Sirt1 protein. However, Sirt1 protein and activity levels were found to be appreciably upregulated when keratinocytes became transformed. This increased Sirt1 activity was associated with decrease in p53 levels in both N/TERT-1 cells which contain normal p53 as well as HaCaT cells with mutated p53. Further, treatment of UV-transformed N/TERT-1 and HaCaT keratinocytes with Sirt1 inhibitor nicotinamide resulted in an induction of cell cycle arrest and apoptosis. Taken together, our data suggested that Sirt1 plays an important role in UV response including UV-induced keratinocyte cell transformation. Based on our study, we suggest that Sirt1 manipulation should be evaluated as a strategy for the management of UV-damages including skin cancer and skin aging.
Recognition of gut microbiota by NOD2 is essential for the homeostasis of intestinal intraepithelial lymphocytes
Authors: Wei Jiang, Xiaqiong Wang, Benhua Zeng, Lei Liu, Aubry Tardivel, Hong Wei, Jiahuai Han, H. Robson MacDonald, Jurg Tschopp, Zhigang Tian, Rongbin Zhou
Journal: The Journal of Experimental Medicine (2013)

NOD2 functions as an intracellular sensor for microbial pathogen and plays an important role in epithelial defense. The loss-of-function mutation of NOD2 is strongly associated with human Crohn’s disease (CD). However, the mechanisms of how NOD2 maintains the intestinal homeostasis and regulates the susceptibility of CD are still unclear. Here we found that the numbers of intestinal intraepithelial lymphocytes (IELs) were reduced significantly in Nod2−/− mice and the residual IELs displayed reduced proliferation and increased apoptosis. Further study showed that NOD2 signaling maintained IELs via recognition of gut microbiota and IL-15 production. Notably, recovery of IELs by adoptive transfer could reduce the susceptibility of Nod2−/− mice to the 2,4,6-trinitrobenzene sulfonic acid (TNBS)–induced colitis. Our results demonstrate that recognition of gut microbiota by NOD2 is important to maintain the homeostasis of IELs and provide a clue that may link NOD2 variation to the impaired innate immunity and higher susceptibility in CD.
Bacterial Endotoxin Activates the Coagulation Cascade through Gasdermin D-Dependent Phosphatidylserine Exposure
Authors: Xinyu Yang, Xiaoye Cheng, Yiting Tang, Xianhui Qiu, Yupeng Wang, Haixia Kang, Jianfeng Wu, Zhongtai Wang, Yukun Liu, Fangping Chen, Xianzhong Xiao, Nigel Mackman, Timothy R. Billiar, Jiahuai Han, Ben Lu
Journal: Immunity (2019)
Long-term prognosis of ulcerative colitis and its temporal changes between 1986 and 2015 in a population-based cohort in the Songpa-Kangdong district of Seoul, Korea
Authors: Jae Myung Cha, Sang Hyoung Park, Kyoung Hoon Rhee, Sung Noh Hong, Young-Ho Kim, Seung In Seo, Kyung Ho Kim, Seung Kyu Jeong, Ji Hyun Lee, Sun Yong Park, Hyunju Park, Joo Sung Kim, Jong Pil Im, Hyuk Yoon, Sung Hoon Kim, Jisun Jang, Jeong Hwan Kim, Seong O Suh, Young Kyun Kim, Byong Duk Ye, Suk-Kyun Yang
Journal: Gut (2019)

No population-based study has evaluated the natural course of UC over three decades in non-Caucasians. We aimed to assess the long-term natural course of Korean patients with UC in a population-based cohort.This Korean population-based, Songpa-Kangdong IBD cohort included all patients (n=1013) newly diagnosed with UC during 1986-2015. Disease outcomes and their predictors were evaluated.During the median follow-up of 105 months, the overall use of systemic corticosteroids, thiopurines and antitumour necrosis factor (anti-TNF) agents was 40.8%, 13.9% and 6.5%, respectively. Over time, the cumulative risk of commencing corticosteroids decreased, whereas that of commencing thiopurines and anti-TNF agents increased. During follow-up, 28.7% of 778 patients with proctitis or left-sided colitis at diagnosis experienced proximal disease extension. A total of 28 patients (2.8%) underwent colectomy, demonstrating cumulative risks of colectomy at 1, 5, 10, 20 and 30 years after diagnosis of 1.0%, 1.9%, 2.2%, 5.1% and 6.4%, respectively. Multivariate Cox regression analysis revealed that extensive colitis at diagnosis (HR 8.249, 95% CI 2.394 to 28.430), ever use of corticosteroids (HR 6.437, 95% CI 1.440 to 28.773) and diagnosis in the anti-TNF era (HR 0.224, 95% CI 0.057 to 0.886) were independent predictors of colectomy. The standardised mortality ratio in patients with UC was 0.725 (95% CI 0.508 to 1.004).Korean patients with UC may have a better clinical course than Western patients, as indicated by a lower colectomy rate. The overall colectomy rate has continued to decrease over the past three decades.
The Psychometric Properties of the ITP Life Quality Index Assessed in a Large Multinational "Real-World" Cohort of Immune Thrombocytopaenia Patients
Authors: Philip Griffiths, Laura Grant, Nicola Bonner, Denise D'Alessio, Quentin A. Hill, Drew Provan, Waleed Ghanima, Nichola Cooper, Ricardo Viana
Journal: Blood (2019)
RNA-Seq reveal the circular RNAs landscape of lung cancer
Authors: Christophe Nicot
Journal: Molecular Cancer (2019)

Few studies have used high-throughput RNA sequencing for functional characterization of patients with non-small cell lung cancer (NSCLC) including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).In a study recently published in Molecular Cancer, Wang and colleagues' work revealed the common and histopathological subtype-specific circular RNA (circRNA) expression patterns between LUAD and LUSC and highlighted the important diagnostic potential of circRNAs in lung cancer [1].To obtain a comprehensive and accurate quantification of circRNAs, the authors analyzed high-throughput RNA sequencing data from 10 pairs of lung tumors and their adjacent normal tissues using five computational tools.Results revealed 17,952 circRNAs including 2593 previously unidentified circRNAs.Using stringent criteria (corrected p-value ≤0.05 and fold change ≥2), differential expression of 50 and 172 circRNAs was identified in tumor tissues of LUAD and LUSC, respectively.In addition, 26 circRNAs were commonly deregulated in both tumors.Moreover, another independent cohort of 67 lung cancer patients' samples were subjected to experimentally validation of RNA-sequencing data.Results were consistent and validated the accuracy and robustness of the circRNA analysis pipeline.The authors also conducted the Receiver Operating Characteristic (ROC) curve analysis of several selected cir-cRNAs and revealed high diagnostic potential of hsa_circ_ 0077837 and hsa_circ_0001821 in discriminating NSCLC from normal tissues.Authors' results also highlighted the potential application of hsa_circ_0001073 and hsa_circ_ 0001495 for diagnostic in the histopathological subtyping of NSCLC.Collectively, this study demonstrated that LUAD and LUSC as the major subtype of NSCLC share a common differential expression pattern, but also have their unique circRNA expression signatures.Identified circRNAs may serve as and new clinical tools for diagnosis of pathological subtypes of NSCLC and therapeutic intervention.
162TiP A phase I study evaluating BI 765063, a first in class selective myeloid SIRPa inhibitor, as standalone and in combination with BI 754091, a programmed death-1 (PD-1) inhibitor, in patients with advanced solid tumours
Authors: A. Marabelle, P. Cassier, J.-P. Delord, C. Jungles, S. Champiat, A. Vinceneux, I. Korakis, R. Huhn, N. Poirier, B. Vasseur, N. Kotecki
Journal: Annals of Oncology (2019)
Re: Carlo Bravi, Emily Vertosick, Nicole Benfante, et al. Impact of Acute Kidney Injury and Its Duration on Long-term Renal Function After Partial Nephrectomy. Eur Urol 2019;76:398–403
Authors: Won Ho Kim, Hyun-Kyu Yoon, Chang Wook Jeong
Journal: European Urology (2019)
A Phase I Study of an Anti-IDO1 Inhibitor (LY3381916) as Monotherapy and in Combination with an Anti-PD-L1 Antibody (LY3300054) in Patients with Advanced Cancer
Authors: N. Kotecki, B. O'Neil, S. Jalal, C. Massard, J. Wallin, A. Szpurka, D. Wang, V. Regnier Galvao, M.S. Xia, K. Crowe, S. Geeganage, T. Doman, L. Gandhi, X. Xu, J. Bendell
Journal: Annals of Oncology (2019)
P1.12-13 The Past, Present, and Future of SCLC and NSCLC Incidence, Mortality, and Prevalence in Denmark During 2006 Through 2030
Authors: A. Green, K. Olsen, G. Persson, M. Bliddal, M. Hornbak, H. Christensen, E. Jakobsen
Journal: Journal of Thoracic Oncology (2019)
Improved transplant survival and long-term disease outcome in children with MHC class II deficiency
Authors: Su Han Lum, Claire Anderson, Peter McNaughton, Karin Regine Engelhardt, Brigid MacKenzie, Helen Watson, Hamoud Al-Mousa, Waleed Al-Herz, Bandar Al-Saud, Reem Mohammed, Daifulah M. Al-Zahrani, Hamza Ali Alghamdi, Loie Goronfolah, Zohreh Nademi, Sahar Habibollah, Aisling M. Flinn, Benjamin Shillitoe, Stephen Owens, Eleri Williams, Marieke Emonts, Sophie Hambleton, Mario Abinun, Terrence Flood, Andrew Cant, Andrew R. Gennery, Mary Slatter
Journal: Blood (2020)
Personal financial conflicts of interest among authors of cancer clinical trials and editorials: scope and relationship to study funding
Authors: Rachel Riechelmann, Lisa Wang, Aoife O'Carroll, Monika Krzyzanowska
Journal: Cancer Research (2007)

948  Background: The growing involvement of the pharmaceutical industry in clinical cancer research has led to concerns regarding scientific integrity of the research enterprise. Here we describe the epidemiology of potential personal financial conflicts of interest (COI) disclosed by authors of clinical cancer studies.  Methods: We reviewed all clinical trials (CTs) and editorials of systemic anticancer and supportive care drugs published in the Journal of Clinical Oncology in a one-year period. We used summary statistics to describe the results and logistic regression to identify factors associated with COI among authors of CTs (source of funding, type of study, continent(s) where the study was conducted and number of authors). The dependent variable was disclosure of at least one COI (any type) per article.  Results: Of the 1,533 articles published betweenJan 2005 and Jan 2006, 332 met our inclusion criteria: 289 (87%) were CTs and 43 (13%) were editorials. At least one COI (any type) was disclosed in 198/289 (69%) CTs and in 22/43 (51%) editorials. The pharmaceutical industry partially or entirely funded 129/289 (45%) CTs. The most common types of COI disclosed by authors were honoraria, consultancy fees and research funds. In a sample of 177 articles published since August 2005, when amount of money received began being reported, the largest monetary levels were reported for research funds. In multivariate analysis, authors of CTs originating in North America (North America vs. Europe: OR=2.9, p=0.002) and those funded entirely (industry vs non-profit organization: OR=13.8, p  Conclusions: Personal financialCOI are common among authors of clinical cancer studies and usually take the form of honoraria, consultancy fees and/or research funds. Source of funding is significantly associated with disclosure of COI.
Utility of intravenous indocyanine green injection in discovering stenosed hepaticojejunal anastomoses following pancreaticoduodenectomy during ERCP
Authors: Naohito Uchida, Yuko Bando, Takaaki Mizuo, Sae Hamaya, Toshiaki Nakatsu
Journal: Endoscopy (2019)

Indocyanine green (ICG) is a green-colored dye that is taken up by hepatic cells when intravenously administered, does not undergo metabolic processes such as conjugation, and is excreted unchanged in the bile [1]. We speculated that ICG could be useful in identifying hepaticojejunal anastomoses, as ICG changes the bile color from yellow to green.
A polyphenol-metal nanoparticle platform for tunable release of liraglutide to improve blood glycemic control and reduce cardiovascular complications in a mouse model of type II diabetes
Authors: Zhiyu He, Tianqi Nie, Yizong Hu, Yang Zhou, Jinchang Zhu, Zhijia Liu, Lixin Liu, Kam W. Leong, Yongming Chen, Hai-Quan Mao
Journal: Journal of Controlled Release (2019)
Abstract I06: Clonal evolution and progression of pancreatic cancer precursor lesions
Authors: Laura D. Wood
Journal: Cancer Research (2019)

Abstract Pancreatic cancer arises from noninvasive precursor lesions that are curable if detected and treated early enough. These precursor lesions include microscopic pancreatic intraepithelial neoplasia (PanIN) and cystic intraductal papillary mucinous neoplasm (IPMN). Interrogation of these lesions can provide critical insights into the earliest stages of pancreatic tumorigenesis and provide a rational foundation for early detection approaches. We have performed comprehensive genomic analyses of PanINs, IPMNs, and associated invasive carcinomas, highlighting several unique features of initiation and progression of pancreatic neoplasms. We show that early-stage precursor lesions contain multiple independent clones, each with distinct mutations, indicating their polyclonal origin. In addition, we identify convergent evolution of tumor suppressor gene loss at later stages of tumorigenesis, as well as subclonal complexity of driver gene mutations and mutations in specific genes limited to invasive cancers. Taken together, these data challenge the traditional monoclonal origin of pancreatic tumors, highlight distinct evolutionary features of precancerous lesions, and transform our understanding of the clonal evolution of pancreatic neoplasia. Citation Format: Laura D. Wood. Clonal evolution and progression of pancreatic cancer precursor lesions [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I06.
Germline genetic patterns underlying familial rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren’s syndrome highlight T cell-initiated autoimmunity
Authors: Yukai Wang, Shaoqi Chen, Jingyao Chen, Xuezhen Xie, Sini Gao, Chengpeng Zhang, Songxia Zhou, Jing Wang, Ruiqin Mai, Qisheng Lin, Jianqun Lin, Marco Matucci-Cerinic, Guohong Zhang, Daniel E Furst
Journal: Annals of the Rheumatic Diseases (2019)

Objectives Familial aggregation of primary Sjögren’s syndrome (pSS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and co-aggregation of these autoimmune diseases (ADs) (also called familial autoimmunity) is well recognised. However, the genetic predisposition variants that explain this clustering remains poorly defined. Methods We used whole-exome sequencing on 31 families (9 pSS, 11 SLE, 6 RA and 5 mixed autoimmunity), followed by heterozygous filtering and cosegregation analysis of a family-focused approach to document rare variants predicted to be pathogenic by in silico analysis. Potential importance in immune-related processes, gene ontology, pathway enrichment and overlap analyses were performed to prioritise gene sets. Results A range from 1 to 50 rare possible pathogenic variants, including 39 variants in immune-related genes across SLE, RA and pSS families, were identified. Among this gene set, regulation of T cell activation (p=4.06×10 −7 ) and T cell receptor (TCR) signalling pathway (p=1.73×10 −6 ) were particularly concentrated, including PTPRC ( CD45 ), LCK , LAT–SLP76 complex genes ( THEMIS , LAT , ITK , TEC , TESPA1 , PLCL1) , DGKD , PRKD1 , PAK2 and NFAT5 , shared across 14 SLE, RA and pSS families. TCR-interactive genes P2RX7 , LAG3 , PTPN3 and LAX1 were also detected. Overlap analysis demonstrated that the antiviral immunity gene DUS2 variant cosegregated with SLE, RA and pSS phenotypes in an extended family, that variants in the TCR-pathway genes CD45 , LCK and PRKD1 occurred independently in three mixed autoimmunity families, and that variants in CD36 and VWA8 occurred in both RA-pSS and SLE-pSS families. Conclusions Our preliminary results define common genetic characteristics linked to familial pSS, SLE and RA and highlight rare genetic variations in TCR signalling pathway genes which might provide innovative molecular targets for therapeutic interventions for those three ADs.
Abstract I08: Molecular subtypes - bench to bedside
Authors: Jen Jen Yeh
Journal: Cancer Research (2019)

Abstract Recent treatment advances in chemotherapy and targeted therapy regimens have provided pancreatic cancer patients and providers with better options. Molecular subtyping for pancreatic cancer has made substantial progress in recent years. With these advances, there is now an opportunity to enable precision medicine approaches for patients with pancreatic cancer. Transcriptomic molecular subtyping is currently an active area of study where several subtyping schemas have been proposed. This talk will present some of these schemas and attempt to reconcile them. Many subtyping approaches rely on the clustering of a new sample with an existing group of samples, the ability to determine the subtype of an individual tumor is limited. In addition, in order to use molecular subtypes in the clinic, subtypes need to be clinically replicable, robust, and have clinical implications. Developing a robust method for subtype classification is needed in order to study the role of molecular subtypes in the context of future clinical trials. Citation Format: Jen Jen Yeh. Molecular subtypes - bench to bedside [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I08.
Cardiovascular Prevention Strategies in Breast Cancer
Authors: Alexandra B. Yin, Abenaa M. Brewster, Ana Barac, Whittney Thoman, Kevin C. Oeffinger, Susan C. Gilchrist
Journal: JACC CardioOncology (2019)

With advances in breast cancer therapy, there has been substantial improvement in cancer-specific prognosis for women with breast cancer. As expected, with greater breast cancer survival, risks for competing causes of death have increased in this group of patients, specifically the risk of
Utility of 90-Day Mortality vs 30-Day Mortality as a Quality Metric for Transcatheter and Surgical Aortic Valve Replacement Outcomes
Authors: Sameer Hirji, Siobhan McGurk, Spencer Kiehm, Julius Ejiofor, Fernando Ramirez-Del Val, Ahmed A. Kolkailah, Natalia Berry, Piotr Sobieszczyk, Marc Pelletier, Pinak Shah, Patrick O’Gara, Tsuyoshi Kaneko
Journal: JAMA Cardiology (2019)

Questions have recently arisen as to whether 30-day mortality is a reasonable metric for understanding institutional practice differences after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR).To examine the utility of 30-day vs 90-day mortality after TAVR and SAVR as a mortality quality metric.This nationally representative, multicenter, cohort study analyzed data from Medicare beneficiaries undergoing TAVR and SAVR procedures from January 1, 2012, to December 31, 2015. Concomitant coronary artery bypass grafting and other heart valve or other major open-heart procedures were excluded. Hospitals that performed fewer than 50 TAVR or 70 SAVR procedures per year were excluded to ensure reliable estimates and to reduce the risks of inflated results because of small institutional sample sizes. Data were analyzed from October 2018 to August 2019.Hospitals were ranked into top- (10%), middle- (80%), and bottom-performing (10%) groups based on their 4-year mean 30-day mortality.Changes in hospital performance rankings at 90 days and 1 year and correlation of 30- and 90-day mortality with 1-year mortality were examined.A total of 30 329 TAVR admissions at 184 hospitals and 26 021 SAVR admissions at 191 hospitals were evaluated. For TAVR, 40 hospitals (21.7%) changed performance rankings at 90 days: 13 (48.1%) in the top-performing group and 8 (29.6%) in the bottom-performing group. At 1 year, 56 hospitals (30.4%), which included 21 (77.8%) in the top-performing group and 12 (44.4%) in the bottom-performing group, changed rankings. Similar findings were observed for SAVR, with an overall 90-day conversion rate of 17.3% and a 1-year rate of 30.3%. These findings persisted after adjusting for the differences in patient risk profiles among the 3 groups. Capturing 90-day events was also more robustly informative regarding expected 1-year outcomes after both TAVR and SAVR, largely owing to the observed plateau in the instantaneous hazard observed beyond this point.The findings suggest that evaluation of hospital performance based on 30-day mortality may underestimate outcomes and therefore substantially misrepresent institutional performance after TAVR and SAVR compared with 90-day mortality, even after risk adjustment. Although 30-day mortality has been validated, 90-day mortality may be a more reliable outcome metric for measuring hospital performance and capturing procedure-related mortality.
Shots, Not Moonshots—The Importance of Broad Population Immunization to Patients Who Undergo Cancer Treatment
Authors: Maresa C. Woodfield, Paul A. Carpenter, Steven A. Pergam
Journal: JAMA Oncology (2019)

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