tbuckley/cabot-search huggingface dataset:
Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma: a study within the National Cancer Institute Cohort Consortium
Authors: Michael B Cook, Matthew J Barnett, Cathryn H Bock, Amanda J Cross, Phyllis J Goodman, Gary E Goodman, Christopher A Haiman, Kay-Tee Khaw, Marjorie L McCullough, Christine C Newton, Marie-Christine Boutron-Ruault, Eiliv Lund, Martin Rutegård, Mark D Thornquist, Michael Spriggs, Carol Giffen, Neal D Freedman, Troy Kemp, Candyce H Kroenke, Loïc Le Marchand, Jin Young Park, Michael Simon, Lynne R Wilkens, Ligia Pinto, Allan Hildesheim, Peter T Campbell
Journal: Gut (2018)

Objective Cross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette smoking with cancer risk. Design This nested case–control study included 296 oesophageal adenocarcinoma cases and 296 incidence density matched controls from seven prospective cohort studies. We quantitated 69 circulating inflammation markers using Luminex-based multiplex assays. Conditional logistic regression models estimated associations between inflammation markers and oesophageal adenocarcinoma, as well as direct and indirect effects of obesity and smoking on risk of malignancy. Results Soluble tumour necrosis factor receptor 2 (sTNFR2) (ORs quartile 4 vs 1 =2.67, 95% CI 1.52 to 4.68) was significantly associated with oesophageal adenocarcinoma. Additional markers close to the adjusted significance threshold included C reactive protein, serum amyloid A, lipocalin-2, resistin, interleukin (IL) 3, IL17A, soluble IL-6 receptor and soluble vascular endothelial growth factor receptor 3. Adjustment for body mass index, waist circumference or smoking status slightly attenuated biomarker–cancer associations. Mediation analysis indicated that sTNFR2 may account for 33% (p=0.005) of the effect of waist circumference on oesophageal adenocarcinoma risk. Resistin, plasminogen activator inhibitor 1, C reactive protein and serum amyloid A were also identified as potential mediators of obesity–oesophageal adenocarcinoma associations. For smoking status, only plasminogen activator inhibitor 1 was a nominally statistically significant (p&lt;0.05) mediator of cancer risk. Conclusion This prospective study provides evidence of a link between systemic inflammation and oesophageal adenocarcinoma risk. In addition, this study provides the first evidence that indirect effects of excess adiposity and cigarette smoking, via systemic inflammation, increase the risk of oesophageal adenocarcinoma.
The Diastolic Murmur of Atrial Septal Defects as Detected by Intracardiac Phonocardiography
Authors: Alfwennevold
Journal: Circulation (1966)

Intracardiac phonocardiography was performed in 18 patients with the secundum type of atrial septal defect. In eight patients a delayed diastolic murmur was recorded in the inflow tract of the right ventricle and was probably due to the increased flow through the tricuspid valve; the murmur was audible at external auscultation in five of the patients. In 13 patients a diastolic murmur was recorded in the right atrium; eight patients had an early diastolic murmur, two patients had a delayed diastolic murmur, and the remaining three patients had both kinds of murmurs. The early diastolic murmur did not correspond in time to the murmur found in the right ventricle and was probably due to the flow through the defect. The delayed diastolic murmur could be due either to the flow through the tricuspid valve or through the defect. None of the atrial diastolic murmurs were audible at external auscultation.
Mechanisms of Coronary Microvascular Dilation Induced by the Activation of Pertussis Toxin–Sensitive G Proteins Are Vessel-Size Dependent
Authors: TatsuyaKomaru, ToshinoriTanikawa, AkihikoSugimura, ToshinobuKumagai, KouichiSato, HiroshiKanatsuka, KunioShirato
Journal: Circulation Research (1997)

G proteins are critically important mediators of many signal transduction systems. In the present study, we investigated the effect of direct activation of pertussis toxin (PTX)–sensitive G protein (GPTX) on coronary arterial microvascular tone in 37 open-chest anesthetized dogs in vivo. Coronary arterial microvessels on the surface of the beating left ventricle were visualized by performing fluorescence coronary microangiography using an intravital microscope with a floating objective system. Microvessels were divided into two groups, small microvessels (inner diameter, ≤130 μm) and large microvessels (inner diameter, >130 μm). Topically applied mastoparan (G protein activator, 10, 30, and 100 μmol/L) produced homogeneous microvascular dilation in a concentration-dependent manner (10 μmol/L, 7.9±2.0%; 30 μmol/L, 10.3±2.4%; and 100 μmol/L, 16.7±4.5% in small microvessels; 10 μmol/L, 5.3±1.2%; 30 μmol/L, 9.8±2.5%; and 100 μmol/L, 15.5±3.9% in large microvessels). These dilations were reversed to constricti...
Abstract 701: An inflammation paradox: Obesity vs. neutrophil-lymphocyte ratio in immunotherapy
Authors: Wungki Park, Vaia Florou, Alfredo Torres, Diana Saravia, Sandra Algaze, Gilberto Lopes
Journal: Cancer Research (2018)

Abstract Background: The dual roles of inflammation in malignancy has been well-described. Neutrophils play a key role in inflammation and carcinogenesis. We previously showed that high NLR may confer resistance to PD1/PDL1 inhibitors in lung cancer patients. In addition, obesity has been shown to produce chronic inflammation and neutrophil dysfunction have been described. The interplay between obesity and neutrophil in solid tumor patients treated with immunotherapy is unknown. Methods: We retrospectively evaluated 408 patients with solid tumors who treated with immunotherapies at the University of Miami. Cox regression was performed to evaluate correlation of obesity (BMI &amp;gt;30) and NLR &amp;lt;5 with Progression Free Survival (PFS) and Overall Survival (OS). Pearson Correlation was used for correlation between BMI and NLR. Results: Median follow-up was 8.6 months. There were head, neck and thoracic (n=257), gastrointestinal (n=32), genitourinary (n=58), skin and musculoskeletal (n=61). There were 230 males, mean age was 65.8. Treatments include nivolumab (n=204), pembrolizumab (n=128), atezolizumab (n=35), and combination with ipilimumab (n=41). There were underweight (BMI&amp;lt;18.5, n=27), normal weight (18.5≤BMI&amp;lt;25, n=186), overweight (25≤BMI&amp;lt;30, n=117), and obese patients (BMI≥30, n=78). Obesity (BMI≥30) and NLR &amp;lt;5 were strongly correlated with better OS with HR: 3.031 and HR: 2.424, respectively. (Table 1) There was trend of better PFS in obese patients, however it was not statistically significant. BMI and NLR showed inverse correlation. (r= -0.172, p=0.001) Conclusions: Surrogates of inflammation, such as obesity and NLR in patients with solid cancer may predict immunotherapy responses. High NLR was associated with adverse clinical outcomes and failure to checkpoint inhibitors, perhaps due to unfavorable tumor-associated neutrophil phenotypes. There was also a strong correlation between obesity and overall survival in these solid tumor patients. Table 1. Multivariate analysisPFSOSFactorHR95% C.I.p-valueHR95% C.I.p-valueECOG&amp;gt;12.188(1.561-3.068)0.00013.031(1.937-4.742)0.0001BMI&amp;lt;301.136(0.806-1.601)0.4682.934(1.484-5.801)0.002NLR≥51.704(1.301-2.230)0.00012.424(1.661-3.538)0.0001 Citation Format: Wungki Park, Vaia Florou, Alfredo Torres, Diana Saravia, Sandra Algaze, Gilberto Lopes, University of Miami. An inflammation paradox: Obesity vs. neutrophil-lymphocyte ratio in immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 701.
Abstract 2919: Discovery of small-molecule compounds targeting c-MYC using a novel cell-based screen
Authors: Biju Mangatt, Anthony D. Pietra, Anna Waszkiewicz, Jon-Paul Jaworski, Sonja Ghidelli-Disse, Thomas J. Berrodin, Christian S. Sherk, Derrick W. Meinhold, Anna Rutkowska-Klute, Shanker K. Sundaram, Gopinath Ganji, Wendy S. Halsey, George P. Livi, William Li, James Mack, Stuart P. Romeril, Elisabeth A. Minthorn, Rakesh Kumar, Gerard C. Drewes, Dirk A. Heerding, Lorena A. Kallal, Carolyn A. Buser, Jesus R. Medina
Journal: Cancer Research (2018)

Abstract Elevated expression of the c-MYC oncogene (either due to gene amplification, translocation, abnormality in upstream signaling pathways and/or protein stabilization) is one of the most common abnormalities in human cancers. Efforts to identify direct pharmacological inhibitors of c-MYC function have not yet yielded drug-like molecules. Therefore, we sought to pursue alternative screening strategies for this classically “undruggable” transcription factor. We developed a novel antibody-based high-throughput HTRF screening assay that specifically detects endogenous c-MYC protein levels in a MYC amplified cancer cell line. Taking advantage of the short half-life of c-MYC, both at the protein and mRNA level, we conducted a cell-based screen of the GSK screening collection to identify compounds that can rapidly decrease c-MYC protein levels. Elimination of false positive hits using stringent triage assays successfully identified two valid hit series exemplified by GSK970 and GSK417. Molecular mode of action studies revealed these molecules inhibit MYC transcription by binding to the minor groove of DNA with AT sequence specificity. Unfortunately, this mechanism of c-MYC inhibition demonstrated poor in vivo translatability as tissue DNA acts as a molecular sink, effectively sequestering compound, and limiting its pharmacodnyamic response. Citation Format: Biju Mangatt, Anthony D. Pietra, Anna Waszkiewicz, Jon-Paul Jaworski, Sonja Ghidelli-Disse, Thomas J. Berrodin, Christian S. Sherk, Derrick W. Meinhold, Anna Rutkowska-Klute, Shanker K. Sundaram, Gopinath Ganji, Wendy S. Halsey, George P. Livi, William Li, James Mack, Stuart P. Romeril, Elisabeth A. Minthorn, Rakesh Kumar, Gerard C. Drewes, Dirk A. Heerding, Lorena A. Kallal, Carolyn A. Buser, Jesus R. Medina. Discovery of small-molecule compounds targeting c-MYC using a novel cell-based screen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2919.
Modification of the Substrate for Maintenance of Idiopathic Human Atrial Fibrillation
Authors: SabineErnst, MichaelSchlüter, FeifanOuyang, AfsanehKhanedani, RiccardoCappato, JoachimHebe, MariusVolkmer, MatthiasAntz, Karl-HeinzKuck
Journal: Circulation (1999)

Background—Catheter ablative techniques to modify the substrate to maintain atrial fibrillation (AF) require the creation of continuous radiofrequency current-induced ablation lines. This study was designed to assess the efficacy and safety of nonfluoroscopic mapping in this setting. Methods and Results—A total of 45 consecutive patients with idiopathic AF were studied. The first 13 underwent ablation confined to the left atrium by creating a circular line isolating the pulmonary vein ostia and a second line connecting the former with the mitral annulus. Subsequently, 12 of these patients underwent a procedure confined to the right atrium (RA), where attempts were made to create an isthmus line between the inferior vena cava and the tricuspid annulus, an anterior line connecting the tricuspid annulus with the superior vena cava, and an intercaval line between the ostia of the inferior and superior venae cavae. In the last 32 patients, only the RA approach was performed. Technical difficulties prevented th...
Lack of Phospholipase A2 Receptor Increases Susceptibility to Cardiac Rupture After Myocardial Infarction
Authors: HidetoMishina, KazuhiroWatanabe, ShunTamaru, YosukeWatanabe, DaisukeFujioka, SoichiroTakahashi, KojiSuzuki, TakamitsuNakamura, Jun-eiObata, KenichiKawabata, YasunoriYokota, OsamuInoue, MakotoMurakami, KohjiHanasaki, KiyotakaKugiyama
Journal: Circulation Research (2014)

Rationale:Recent evidence indicates that the biological effects of secretory phospholipase A2 (sPLA2) cannot be fully explained by its catalytic activity. A cell surface receptor for sPLA2 (PLA2 receptor 1 [PLA2R]) and its high-affinity ligands (including sPLA2-IB, sPLA2-IIE, and sPLA2-X) are expressed in the infarcted myocardium. Objective:This study asked whether PLA2R might play a pathogenic role in myocardial infarction (MI) using mice lacking PLA2R (PLA2R–/–). Methods and Results:MI was induced by permanent ligation of the left coronary artery. PLA2R–/– mice exhibited higher rates of cardiac rupture after MI compared with PLA2R wild-type (PLA2R+/+) mice (46% versus 21%, respectively; P=0.015). PLA2R–/– mice had a 31% decrease in collagen content and a 45% decrease in the number of α-smooth muscle actin–positive fibroblasts in the infarcted region compared with PLA2R+/+ mice. PLA2R was primarily found in myofibroblasts in the infarcted region. PLA2R–/– myofibroblasts were impaired in collagen-dependen...
Abstract 2182: DigiPico: A whole-genome sequencing approach to investigate microscopic residual chemotherapy resistance disease in ovarian cancer
Authors: Mohammad KaramiNejadRanjbar, Donatien Chedom Fotso, Yuhao Zheng, Christopher Yau, Ahmed Ahmed
Journal: Cancer Research (2018)

Abstract Microscopic residual chemotherapy resistance disease (MRCD) following cancer therapy predisposes to recurrence. Genome analysis of MRCDs could, therefore, give insights into evolutionary mechanisms that might govern this process. However, to date, this has largely been restricted to studies utilizing targeted sequencing of known somatic mutations due to the challenges of whole-genome sequencing of subnanogram quantities of DNA. A previous report showed that obtaining accurate whole-genome sequencing is possible from as little as 10 to 20 cells with the added advantage of obtaining reconstructed long fragment reads. Adopting this technology, we were able to optimize a procedure to accurately obtain high-quality whole-genome sequencing data from minimally available clinical samples such as MRCDs, termed DigiPico. Using DigiPico, we were able to perform sequencing on several post-chemotherapy MRCDs and single tumor islets from a high-grade serous ovarian cancer (HGSOC) tumor. The data were found to be highly accurate, with over 96% of the single-nucleotide polymorphisms (SNPs) being detected in DigiPico sequencing results despite the extremely low amount of material available. Moreover, we found that DigiPico can be used for calculation of allele fractions with a consistency rate of up to 84% as opposed to a consistency rate of only 47% for when a standard multiple displacement amplification of similar amount of DNA is used during library preparation. The high-quality allele fraction information from DigiPico was then used to predict the copy number variation (CNV) in these clinical samples. Here, we showed the power of DigiPico for accurate SNP calling and CNV prediction from post-chemotherapy MRCDs and single tumur islets of a HGSOC tumor, the latter of which is extremely important for studying HGSOC as these tumors often show a great degree of structural alterations. This information can now be used for better understanding of how MRCDs might be able to remain unharmed during the course of chemotherapy and initiate recurrence after completion of treatment, which in turn can allow us to design better treatment strategies for HGSOC patients. Citation Format: Mohammad KaramiNejadRanjbar, Donatien Chedom Fotso, Yuhao Zheng, Christopher Yau, Ahmed Ahmed. DigiPico: A whole-genome sequencing approach to investigate microscopic residual chemotherapy resistance disease in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2182.
Promoting FIT Colorectal Cancer Screening
Authors: Rita F. Redberg
Journal: JAMA Internal Medicine (2018)

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Induction of JAB/SOCS-1/SSI-1 and CIS3/SOCS-3/SSI-3 Is Involved in gp130 Resistance in Cardiovascular System in Rat Treated With Cardiotrophin-1 In Vivo
Authors: IchiroHamanaka, YoshihikoSaito, HideoYasukawa, IchiroKishimoto, KoichiroKuwahara, YoshihiroMiyamoto, MasakiHarada, EmikoOgawa, NoboruKajiyama, NobukiTakahashi, TakehikoIzumi, RikaKawakami, IzuruMasuda, AkihikoYoshimura, KazuwaNakao
Journal: Circulation Research (2001)

Abstract—CIS (cytokine-inducible SH2 protein), SOCS (suppressor of cytokine signaling), or SSI (signal transducers and activators of transcription [STAT]-induced STAT inhibitor) proteins are a family of cytokine-inducible negative regulators of cytokine signaling via Janus kinase (JAK)-STAT pathways. Given the evidence that the JAK-STAT pathway plays a critical role in the cardiovascular system, the primary objective of this study was to assess the effects of the CIS family on JAK-STAT signaling in the cardiovascular system in rats treated with cardiotrophin-1 (CT-1), an interleukin-6 family of cytokines. Intravenous injection of 20 μg/kg body weight of CT-1 induced a transient, marked increase in STAT3 activation in various tissues, including heart and lung, and subsequent upregulation of 2 members of the CIS family, JAK-binding protein (JAB)/SOCS-1/SSI-1 and CIS3/SOCS-3/SSI-3, in the same tissues. It was also observed that CIS3 was directly associated with JAK2 in vivo. Pretreatment with the same dose o...
High acquisition rate of extended-spectrum β-lactamase-producing Enterobacteriaceae among French military personnel on mission abroad, without evidence of inter-individual transmission
Authors: N. Maataoui, A. Mayet, S. Duron, H. Delacour, F. Mentré, C. Laouenan, D. Desvillechabrol, T. Cokelaer, J.B. Meynard, A. Ducher, A. Andremont, L. Armand-Lefèvre, A. Mérens
Journal: Clinical Microbiology and Infection (2018)
Abstract 4243: Association of oral health with lung cancer risk: Results from the Southern Community Cohort Study
Authors: Hyung-Suk Yoon, Wanqing Wen, Jirong Long, Wei Zheng, William J. Blot, Qiuyin Cai
Journal: Cancer Research (2018)

Abstract Increasing evidence suggests that oral health may be associated with cancer and other chronic diseases. Oral bacterial infections, which induce inflammation of the gums and tooth loss, can progress to systemic inflammation. In addition, poor oral health is often the result of smoking and/or limited access to regular dental care. Previous studies have suggested that poor oral health may increase the risk of lung cancer among individuals of European and Asian descent, but the evidence remains elusive. In this nested case-control study, we investigated whether oral health status was associated with lung cancer risk among African Americans and European Americans and whether the association varied by race and smoking habits. A total of 403 incident lung cancer cases and 1,612 matched controls from the Southern Community Cohort Study were included in the current study. The controls were matched to cases on age, sex, race, and recruitment site. Multivariate conditional logistic regression models were fitted to evaluate the risk of lung cancer linked to tooth loss, tooth decay, and history of periodontal disease (gingivitis or periodontitis). Stratified analyses were conducted by race, smoking status, and pack-years, and the interactions of these variables with oral health were further evaluated. Tooth loss was significantly associated with an increased risk of lung cancer. Compared to those without any loss of teeth, the odds ratio (OR) of loss of &amp;gt;10 teeth was 1.64 (95% confidence interval [CI]: 1.00-2.69) after adjusting for confounders. Tooth decay was also significantly associated with increased lung cancer risk. Those with ≥ 6 decaying teeth had an OR of 1.65 (95% CI: 1.18-2.31), compared to those with no tooth decay. An increased lung cancer risk was significantly associated with a history of periodontal disease (OR: 1.44, 95% CI: 1.09-1.19). While there was no evidence of interaction by race, the increase in risk associated with tooth loss, tooth decay, and periodontal disease was observed only among smokers who had smoked more than the race-specific median pack-year. Results from our study indicate that poor oral health, as measured by tooth loss, tooth decay, and periodontal disease is associated with an increased risk of lung cancer and that this association is more evident among heavy smokers. Citation Format: Hyung-Suk Yoon, Wanqing Wen, Jirong Long, Wei Zheng, William J. Blot, Qiuyin Cai. Association of oral health with lung cancer risk: Results from the Southern Community Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4243.