tbuckley/cabot-search huggingface dataset:
Abstract 5247: Aspirin use and estrogen receptor-negative breast cancer risk in African American women
Authors: Kimberly A. Bertrand, Traci N. Bethea, Hanna Gerlovin, Patricia Coogan, Lucile L. Adams-Campbell, Lynn Rosenberg, Julie R. Palmer
Journal: Cancer Research (2018)

Abstract Introduction: Use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been hypothesized to be associated with reduced risk of breast cancer; however, results of epidemiological studies have been mixed. Further, few previous studies investigated these associations among African American women and no studies that included African Americans evaluated whether associations differ by estrogen receptor (ER) status. Methods: To assess the relation of aspirin use to risk of ER+ and ER- breast cancer in African American women, we conducted a prospective analysis within the Black Women's Health Study, an ongoing nationwide cohort of 59,000 black women that began in 1995. On baseline and biennial follow-up questionnaires, women reported regular aspirin use (defined as use at least three days per week) and years of use. Acetaminophen use was queried similarly. Among women with available information on aspirin use, 1701 invasive breast cancers occurred during follow-up through 2015, including 962 ER+ and 492 ER- tumors. All cancers were confirmed through pathology reports or state cancer registry data. We used age-stratified Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of aspirin use with risk of ER+ and ER- breast cancer. All models adjusted for age at menarche, oral contraceptive use, parity, age at first birth, estrogen plus progestin use, body mass index, alcohol consumption, and use of other NSAIDs. Results: Compared to never use, current regular use of aspirin was associated with lower risk of breast cancer overall (HR 0.87; 95% CI 0.76, 1.00). The association was driven by a statistically significant inverse association for ER- breast cancer (HR 0.76; 95% CI 0.58, 0.99); for ER+ breast cancer, the corresponding HR was 0.92 (95% CI 0.77, 1.09). In contrast, we found no associations with acetaminophen use. Conclusions: Our observation of reduced risk of ER- breast cancer in relation to current regular use of aspirin is consistent with anti-inflammatory effects of aspirin, rather than hormone-dependent pathways. Aspirin may represent a potential opportunity for chemoprevention of ER- breast cancer; however, these findings require corroboration in additional studies. Citation Format: Kimberly A. Bertrand, Traci N. Bethea, Hanna Gerlovin, Patricia Coogan, Lucile L. Adams-Campbell, Lynn Rosenberg, Julie R. Palmer. Aspirin use and estrogen receptor-negative breast cancer risk in African American women [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 5247.
Abstract 1198: Rare isn't rare: Rare cancers compose over 50% of all U.S. diagnoses
Authors: Katherine Arline, Emily Zeme, Robert L. Treuting, Rodrigo Bravo, Jamie Barber, Christopher Higginson, Jon Goetz, William Siders, Johanne Kaplan
Journal: Cancer Research (2018)

Abstract Rare cancers are an understudied and deadly public health problem. Estimates for the percentage of cancer diagnoses that are rare vary depending upon the source cited and the definition of what constitutes a rare cancer. A frequently cited report states that 25% of all adult cancers are rare. However, given the ever-changing landscape of cancer biology and as a result of changes in disease classification, oft-cited percentages underestimate the burden of rare cancers. To address this discrepancy, we reviewed the most recent publicly available data regarding the incidence of all cancers in the United States. Following the NCI definition of a rare disease as one affecting fewer than 15 persons per 100,000 per year, for 2017, a cancer affecting 48,952 or fewer is classified as rare. We considered each cancer individually, acknowledging subtypes based upon the criteria of scientifically accepted definitions, treatments, and histology. We then compiled statistics for each type and subtype. By this method, the total number of estimated new cancer patients in 2017 was 1,685,346, which differed only 0.2% from the Cancer.gov's publicly available estimate of 1,688,780. However, in contrast to previously published data that indicated that 60 of 71 cancer types were rare, we identified a total of 347 cancers, of which 337 were rare. The estimate for rare cancer diagnoses in the U.S. per year was therefore 875,084. Ultimately, 51.9% of all cancer diagnoses are classified as rare cancers by this method. In addition, of 52 major groupings of cancer, 35 (67.3%) disproportionately affect minorities in terms of incidence or overall survival. Seven groupings exclusively or almost exclusively affect women, and 7 additional groups display disproportionate incidence or negative outcomes in women. In addition, while many cancers affect children, and while all cancer in children is rare, at least 55 cancers exclusively or frequently affect children. This analysis clearly shows that the incidence of rare cancer in the United States is widely misunderstood and that cancer in total disproportionately affects historically underserved populations. Treatment options are needed for each form of cancer and should be developed based on a thorough understanding of each disease's biology. In addition, efforts to understand and address the origins of demographic disparities can help reduce disease burden. Citation Format: Katherine Arline, Emily Zeme, Robert L. Treuting, Rodrigo Bravo, Jamie Barber, Christopher Higginson, Jon Goetz, William Siders, Johanne Kaplan. Rare isn't rare: Rare cancers compose over 50% of all U.S. diagnoses [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 1198.
Abstract 3145: Characterization of novel immune checkpoint receptors within the breast cancer tumor microenvironment
Authors: Austin D. Williams, Jean S. Campbell, Lauri D. Aicher, Kyle K. Payne, Jose R. Conejo-Garcia, Robert H. Pierce, Julia Tchou
Journal: Cancer Research (2018)

Abstract Introduction. The interruption of immune checkpoint receptor (ICR)/ligand interaction within the tumor microenvironment has become an important immunotherapy strategy. In breast cancer (BC), neither the ICR phenotype of immune cells of each BC subtype nor the associated immune response is fully characterized. We hypothesize that there are differences in ICR phenotypes between BC subtypes. Methods. To analyze the expression of ICRs (i.e. PDCD1 (PD-1), TIGIT, HAVCR2 (Tim-3), and LAG3 in the tumor microenvironment (TME) of BC, the 956- patient BC cohort of The Cancer Genome Atlas (TCGA) gene expression data was analyzed and normalized against CD3E, a T-cell specific transcript. As validation, we examined various ICR by flow cytometry on 14 matched dissociated breast tumor and peripheral blood mononuclear cells (PBMC) and compared differences across BC subtypes with t-test and ANOVA. In addition, differential gene expression and multispectral analysis were investigated using FFPE specimens and the NanoString and Vectra platforms. Results. TCGA data revealed a higher expression of TIGIT, LAG3 and PD-1 in triple-negative breast cancer (TNBC) when compared to other subtypes (p &amp;lt;0.001, Table 1). PD-L1 (CD274) expression was higher in TNBC than ER/PR+/Her2- cancer (p=-0.008). On flow cytometry, there was a higher co-expression of TIGIT and Tim-3 on CD4 T cells in TNBC than all other subtypes (p=0.003) while ER/PR+Her2- cancers had the highest CD4 expression of TIGIT alone (p=0.04). Compared to ER/PR+Her2- cancers, TNBC had increased expression of transcripts associated with myeloid derived suppressor cells, and decreased expression of transcription factors that regulate lineage specification for CD4 helper T cells. Conclusions. In addition to PD-1, we demonstrated that other ICRs may play significant roles in TME of Her2+ and TNBC BC subtypes. Our results support the development of novel anti-ICR therapy which may synergize with current treatment strategies against these unfavorable BC subtypes. Citation Format: Austin D. Williams, Jean S. Campbell, Lauri D. Aicher, Kyle K. Payne, Jose R. Conejo-Garcia, Robert H. Pierce, Julia Tchou. Characterization of novel immune checkpoint receptors within the breast cancer tumor microenvironment [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 3145.
Peroral endoscopic myotomy for the treatment of achalasia patients with Roux-en-Y gastric bypass anatomy
Authors: Omid Sanaei, Peter Draganov, Rastislav Kunda, Dennis Yang, Mouen Khashab
Journal: Endoscopy (2018)

Abstract Background The outcome of peroral endoscopic myotomy (POEM) in patients with prior Roux-en-Y gastric bypass (RYGB) is not known and some experts have recommended against its performance in this patient population because of the risk of postoperative regurgitation. The aim of this study was to report on the outcomes of POEM in patients with RYGB anatomy. Methods Patients with RYGB anatomy who underwent POEM for the treatment of achalasia at three tertiary centers were included. POEM was performed in standard fashion using the anterior or posterior approach. Clinical response was defined by a decrease in Eckardt score to ≤ 3. Results of esophageal acid exposure testing/pH-impedance and manometric testing after POEM were reported when available. Results A total of 10 achalasia patients with prior RYGB surgery underwent POEM. All procedures were technically successful with anterior myotomy performed in seven patients. The mean submucosal tunnel length and myotomy length were 12.9 cm and 11.1 cm, respectively. The mean procedure time was 72 minutes and mean length of hospital stay was 1.5 days. Clinical success was achieved in all 10 patients with a significant decrease in Eckardt score from 6.5 to 1 (P &lt; 0.001). None of the patients experienced post-procedural regurgitation. Post-procedural pH testing was obtained in six patients and was normal in all of them. Conclusions This study suggests the feasibility, safety, and efficacy of POEM in patients with prior RYGB surgery. The risk of gastroesophageal reflux disease in these patients seems to be minimal after POEM.
Failure to Prevent Progressive Dilation of Ascending Aorta by Aortic Valve Replacement in Patients With Bicuspid Aortic Valve: Comparison With Tricuspid Aortic Valve
Authors: HisayoYasuda, SatoshiNakatani, MarieStugaard, YukoTsujita-Kuroda, KoBando, JunjiroKobayashi, MasakazuYamagishi, MasafumiKitakaze, SoichiroKitamura, KunioMiyatake
Journal: Circulation (2003)

Background— Patients with bicuspid aortic valve (BAV) have been frequently complicated with ascending aortic dilation possibly because of hemodynamic burdens by aortic stenosis (AS) or regurgitation (AR) or congenital fragility of the aortic wall. Methods and Results— To clarify if the aortic dilation could be prevented by aortic valve replacement (AVR) in BAV patients, we studied 13 BAV (8 AR dominant, 5 AS dominant) and 14 tricuspid aortic valve (TAV) patients (7 AR, 7 AS) by echocardiography before and after AVR (9.7±4.8 years). We also studied 18 BAV (11 AR, 7 AS) without AVR. Diameters of the sinuses of Valsalva, sinotubular junction and the proximal aorta were measured. The annual dilation rate was calculated by dividing changes of diameters during the follow-up period by the body surface area and the observation interval. We found that aortic dilation in BAV patients tended to be faster than that in TAV patients, although a significant difference was found only at the proximal aorta (0.18±0.08 vers...
Abstract 1954: Functional analyses of <i>CLDN18-ARHGAP26</i> fusion gene in gastric cancers
Authors: Izuma Nakayama, Eiji Shinozaki, Tetsuo Mashima, Tokuichi Kawaguchi, Seiji Sakata, Noriko Yamamoto, Satoko Baba, Akito Dobashi, Yuki Togashi, Minoru Sugawara, Shunji Takahashi, Kensei Yamaguchi, Kengo Takeuchi, Tetsuo Noda
Journal: Cancer Research (2018)

Abstract [Introduction]Comprehensive molecular analyses by TCGA have classified Gastric Cancers (GC) into 4 groups: EB virus -associated (EBV), Microsatellite instability (MSI), Genomically stable (GS) and Chromosomal instability (CIN). Among these 4 subtypes, patients with GS subtype have few actionable genetic alterations and thus a limited number of molecular-targeted treatments are available. A fusion gene between CLDN18 and ARHGAP26 was first reported by TCGA to be enriched in GS subtype (13.8%), but the prospective functions of this gene product remain unknown. [Methods]We have previously established 124 GC-Patient derived xenografts (PDXs) from surgically resected specimens in our institute. There are various types of GCs in the PDX panel, including intestinal and diffuse type tumors or tumors of primary and metastatic site. In an attempt to assess roles of CLDN18-ARHGAP26 fusion gene in gastric cancers, we used the cultured cells obtained from GC-PDXs. We first prepared tissue micro-array of formalin-fixed and paraffin-embedded (FFPE) specimen of PDXs and screened for the patients harboring a CLDN18-ARHGAP26 fusion genes by FISH and RT-PCR. In addition, fusion positive cases were sequenced to determine the breakpoints by direct sequencing. Then, we conducted several functional analyses, including assays for cellular proliferation and mobility, by RNAi-knockdown experiments. [Results]Among 124 GC-PDXs, we detected two CLDN18-ARHGAP26 fusion positive cases. Both of these 2 cases were derived from tumors with diffuse-type GC patient and had identical breakpoint between CLDN18 (exon 5) and ARHGAP26 (exon 10). We successfully established cell lines of these 2 cases. Furthermore, we would verify that PDX derived cells preserved the original patient properties, as transplantation of the PDX-derived cells histologically recapitulated the original tumors. To address its function, we introduced siRNA into cultured cells to reduce their protein levels. Our data so far indicate that the CLDN18-ARHGAP26 fusion might promote anchorage independent cell growth. [Conclusion] The CLDN18-ARHGAP26 fusion gene potentially contributes to malignant phenotypes of GC. Further analyses in vivo are awaited. Citation Format: Izuma Nakayama, Eiji Shinozaki, Tetsuo Mashima, Tokuichi Kawaguchi, Seiji Sakata, Noriko Yamamoto, Satoko Baba, Akito Dobashi, Yuki Togashi, Minoru Sugawara, Shunji Takahashi, Kensei Yamaguchi, Kengo Takeuchi, Tetsuo Noda. Functional analyses of CLDN18-ARHGAP26 fusion gene in gastric cancers [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 1954.
Abstract 5398: Companion diagnostic for predicting the efficacy of mTOR inhibitor in neuroendocrine tumor
Authors: I-Hua Liu, Jia-Ming Chang
Journal: Cancer Research (2018)

Abstract Neuroendocrine tumor (NET) is having both characterizations of hormone and neurotransmitter secretion. The mTOR, a serine-threonine kinase inhibitor, was used for treating the NET tumors by affecting angiogeneic blood vascular vessels as a disrupting agent and killing the tumor cells by inhibiting the mTOR signalling. Everolimus is a U.S. FDA-approved drug for treating advanced breast cancer, which is investigated for use in NET treatment. The efficacy will be evaluated by exosome reflecting the tumor microenvironment secreted into blood circulation. NCI-H727 cells are a kind of NET tumor that show the secretion of chromogranin A (CgA) and serotonin. By profiling of exosome with miRNA, the efficacy may be predicted by the level of miRNA. Here, we demonstrated the pattern of miRNA profile in everolimus-treated NCI-H727 cells. MIR192 and MIR375 were consistently secreted in exosomes with a high level. A panel of miRNA, MIR24-2, MIR3131, and MIR708, was increased and showed a change greater than 0.5 fold compared with untreated cells. In conclusion, by analyzing the pattern of miRNA in exosomes, the efficacy of drug can be monitored during the treatment. A new therapeutic strategy can be tailored according to the miRNA pattern. Citation Format: I-Hua Liu, Jia-Ming Chang. Companion diagnostic for predicting the efficacy of mTOR inhibitor in neuroendocrine tumor [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 5398.
Abstract 18917: Multimodality Imaging in ICD Implantation Decision Making in Heart Failure Patients: Role of 123-Iodine Metaiodobenzylguanidine Imaging and Cardiac Magnetic Resonance Imaging
Authors: Nicolò Salvi, Paola Scarparo, Ilaria Birtolo, Francesco Adamo, Antonio Fusto, Alessandra Cinque, Viviana Frantellizzi, Paolo Severino, Massimo Mancone, Ilaria Mancini, Simone Calcagno, Giuseppe de Vincentis, Francesco Fedele
Journal: Circulation (2016)

Introduction: According to guidelines, implantable cardioverter defibrillator (ICD) is recommended in prevention of sudden cardiac death (SCD) in heart failure (HF) patients (pts). Guidelines have ...
Abstract 16485: Hyperinsulinemia Reduces Autophagy in Insulin Resistant Hearts Through Insulin Growth Factor 1 Receptor (IGF-1R) Signaling
Authors: Karla Maria Pires, Marcio Augusto Buffolo, Shaobo Pei, Crystal Sloan, Brandon Henrie, Sihem Boudina
Journal: Circulation (2015)

Introduction: Diabetes is a leading cause of mortality and morbidity worldwide with over 50% of deaths in diabetic patients being caused by cardiovascular complications. The mechanisms underlying the high incidence of diabetic cardiac dysfunction remain relatively obscure but may involve altered autophagy. Macro-autophagy (referred to as autophagy) is a regulated intracellular catabolic pathway for the turnover of long-lived proteins, macromolecular aggregates, and damaged organelles. Hypothesis: Taking advantage TIRKO mice (a mouse model of total cardiac ablation of insulin receptors [IRs]), we aimed to investigate the impact of myocardial insulin resistance and systemic hyperinsulinemia (SH) on cardiac autophagy. Results: Basal and fasting-induced autophagy were significantly reduced in TIRKO hearts, as evidenced by reduced LC3II/LC3I ratios and increased P62 accumulation. As TIRKO mice develop SH, we next sought to determine whether this reduces autophagy independently of the absence of IRs. Thus, we used mice with cardiomyocytes-specific deletion of IRs (CIRKO mice) but without SH or (ob/ob) mice that have IRs in the heart but develop SH. We demonstrated that cardiac autophagy reduction is indeed caused by systemic SH as its level was unaltered in CIRKO hearts but reduced in (ob/ob) hearts. Because of the absence of IRs in TIRKO hearts and the degree of insulin resistance in (ob/ob) hearts, we hypothesized that the reduction of cardiac autophagy by SH is mediated by the IGF-1R signaling. Indeed, IGF-1R phosphorylation was enhanced in both TIRKO and (ob/ob) hearts but not in CIRKO hearts. To begin to understand the functional role of attenuated autophagy in TIRKO hearts, we further decreased autophagosomes clearance by treating mice with the lysosomal clearance inhibitor chloroquine. Treatment of TIRKO mice with chloroquine for 4 hours massively increased LC3I and P62 levels, promoted cells death and decreased mitochondrial clearance. Conclusions: Taken together, these results suggest that hyperinsulinemia-mediated reduction in cardiac autophagy can be adaptive to suppress sustained autophagy activation by insulin resistance but can become maladaptive if the heart is challenged by a reduction in lysosomal degradation.
The Dissection of the Atrioventricular Node Bundle and Bundle Branches in the Human Heart
Authors: Jerroldwidran, Mauricelev
Journal: Circulation (1951)

The A-V node, bundle and bundle branches were grossly dissected in 41 human hearts. The method for this dissection is described. Given also are the sizes of the individual structures with advancing age. These structures grow more slowly than the remainder of the myocardium.
Statistical Methods for Cardiovascular Researchers
Authors: LemMoyé
Journal: Circulation Research (2016)

Rationale:Biostatistics continues to play an essential role in contemporary cardiovascular investigations, but successful implementation of biostatistical methods can be complex. Objective:To present the rationale behind statistical applications and to review useful tools for cardiology research. Methods and Results:Prospective declaration of the research question, clear methodology, and study execution that adheres to the protocol together and serve as the critical foundation of a research endeavor. Both parametric and distribution-free measures of central tendency and dispersion are presented. T testing, ANOVA, and regression analyses are reviewed. Survival analysis, logistic regression, and interim monitoring are also discussed. Finally, common weaknesses in statistical analyses are considered. Conclusions:Biostatistics can be productively applied to cardiovascular research if investigators (1) develop and rely on a well-written protocol and analysis plan, (2) consult with a biostatistician when necess...
Abstract 18586: Mitral Peak A Wave Velocity Immediate After Radiofrequency Catheter Ablation to Predict Atrial Fibrillation Recurrence
Authors: Jong-Ho Nam, Byung-Jun Kim, Kang-Un Choi, Hyu-Hwan Park, Chan-Hee Lee, Jang-Won Son, Ung Kim, Jong-Seon Park, Dong-Gu Shin, Young-Jo Kim, Hyong-Jun Kim, Jeong-Hwan Cho, Sang-Wook Kang, Jung-Hyun Choi
Journal: Circulation (2016)

Introductions: Radiofrequency catheter ablation (RFCA) has been used to treat patients with atrial fibrillation (AF), and AF recurrence after ablation is an issue of concern. Measuring echocardiographic parameters one day following RFCA, including mitral peak A wave velocity, is of interest to determine the risk of recurrent AF. Methods: During the period of January 2013 and January 2015, we enrolled 68 patients who underwent RFCA and received serial echocardiographic measurements before RFCA and 24 hours after RFCA, retrospectively. AF recurrence, defined as any documented atrial tachyarrhythmias lasting > 30 seconds after 12 weeks following RFCA, was evaluated for one-year follow up. Results: AF recurrence after 12 weeks was 29.4%. Peak A wave velocities were significantly lower one day after following RFCA in patients with AF recurrence compared to those with sinus rhythm (0.38±0.14 vs 0.50±0.17m/sec, p=0.009). Left atrial volume index (LAVI) and mitral peak E wave velocity were significantly increased...
Mucosal neuromas of tongue and lips: a diagnostic clue to MEN2B
Authors: Rami Alrezk, John Glod, Karel Pacak
Journal: BMJ (2018)

A 19 year old man with multiple endocrine neoplasia type 2 (MEN2B) presented for follow-up at the endocrine clinic.

The patient had a characteristic MEN2B phenotype; tongue lesions (fig 1), tall stature, …