tbuckley/cabot-search huggingface dataset:
Mutation Load and a Functional T Effector Signature May Distinguish Immunologically Distinct and Clinically Relevant Lymphoma Subsets
Authors: Chris Bolen, Ronald McCord, Garrett Frampton, Richard Bourgon, Elizabeth A. Punnoose, Edith Szafer-Glusman, Pierre Sujobert, Luc Xerri, Sarah Huet, Gilles Salles, Jeffrey M Venstrom
Journal: Blood (2016)
GINA 2019: a fundamental change in asthma management
Authors: Helen K. Reddel, J. Mark FitzGerald, Eric D. Bateman, Leonard B. Bacharier, Allan Becker, Guy Brusselle, Roland Buhl, Alvaro A. Cruz, Louise Fleming, Hiromasa Inoue, Fanny Wai-san Ko, Jerry A. Krishnan, Mark L. Levy, Jiangtao Lin, Søren E. Pedersen, Aziz Sheikh, Arzu Yorgancioglu, Louis-Philippe Boulet
Journal: European Respiratory Journal (2019)

<b>GINA no longer recommends treating adults/adolescents with asthma with short-acting bronchodilators alone. Instead, they should receive symptom-driven (in mild asthma) or a daily corticosteroid-containing inhaler, to reduce risk of severe exacerbations.</b>http://bit.ly/310LLzE
Compartmentalization of tumor cells to the CSF or peripheral blood of a breast cancer patient with CNS metastasis.
Authors: Joshua Allen, Akshal Patel, David Dicker, Jonas Sheehan, Michael J. Glantz, Wafik El-Deiry
Journal: Journal of Clinical Oncology (2012)

e11544 Background: We recently adapted the CellSearch system to detect cerebrospinal fluid tumor cells (CSFTCs) in breast cancer patients with CNS metastases and found that the CSFTCs correlate with disease burden. Here, we present the enumeration of CSFTCs and peripheral blood tumor cells (PBTCs) in a patient with metastatic breast cancer during treatment with intrathecal (IT) chemotherapy. Methods: We enumerated CSFTCs and PBTCs in a patient with ER+, Her2-, BRCA2+ breast cancer and CNS metastases who received IT chemotherapy and systemic chemoradiation. The patient was initially diagnosed with locally advanced breast cancer and underwent bilateral mastectomies followed by AC-T one year prior to CNS relapse. Tumor cell enumeration was conducted every 1-2 weeks from 7.5mL of peripheral blood or 9mL of CSF along with CSF cytology, Karnofsky performance status (KPS), neurologic examination and radiographic studies during the IT chemotherapy and subsequent systemic chemoradiation. Results: At the beginning of the IT chemotherapy the patient presented with diplopia, gait ataxia, 7 th facial nerve palsy, confusion, and intractable headaches, an initial burden of 19570 CSFTCs and 10-45 PBTCs, a KPS of 80, and no systemic disease. Tumor cell counts dropped rapidly in response to IT therapy alone to 0-1 CSFTCs and 3 PBTCs, all neurologic symptoms resolved, and the KPS increased to 90. The patient subsequently suffered progression of systemic disease with development of bone and brachial plexus metastases. PBTCs rose from 3 to 64 during this same period, whereas CSFTCs remained at 0-1. The CA 27-29 level increased from 111 to 214. CSF cytology and neuro-radiographic imaging cleared in the face of progressive systemic disease. Conclusions: There was a compartmentalization of metastatic tumor cells to either the blood or the CSF in this patient. We hypothesize that tumor cells in the CSF or peripheral blood migrate to the untreated compartment during compartmentalized therapy, resulting in disease recurrence in the untreated compartment. Preliminary data on other patients supports this hypothesis, which may represent an important mechanism for disease recurrence in patients with potentially curable disease.
Anti-tumor Activity of the Type I PRMT Inhibitor, GSK3368715, Synergizes with PRMT5 Inhibition through MTAP Loss
Authors: Andrew Fedoriw, Satyajit R. Rajapurkar, Shane O'Brien, Sarah V. Gerhart, Lorna H. Mitchell, Nicholas D. Adams, Nathalie Rioux, Trupti Lingaraj, Scott A. Ribich, Melissa B. Pappalardi, Niyant Shah, Jenny Laraio, Yan Liu, Michael Butticello, Chris L. Carpenter, Caretha Creasy, Susan Korenchuk, Michael T. McCabe, Charles F. McHugh, Raman Nagarajan, Craig Wagner, Francesca Zappacosta, Roland Annan, Nestor O. Concha, Roberta A. Thomas, Timothy K. Hart, Jesse J. Smith, Robert A. Copeland, Mikel P. Moyer, John Campbell, Kim Stickland, James Mills, Suzanne Jacques-O’Hagan, Christina Allain, Danielle Johnston, Alejandra Raimondi, Margaret Porter Scott, Nigel Waters, Kerren Swinger, Ann Boriack-Sjodin, Tom Riera, Gideon Shapiro, Richard Chesworth, Rabinder K. Prinjha, Ryan G. Kruger, Olena Barbash, Helai P. Mohammad
Journal: Cancer Cell (2019)
Abstract 10984: NF-kappa B Inhibitors as a Novel Therapeutic Agent in the Acute Phase of Kawasaki Disease
Authors: Yukako Yoshikane, Rajendra Bhatnagar, Mitsuhisa Koga, Tamaki Cho, Seiji Haraoka, Junichi Hashimoto, Tatsuki Miyamoto, Shinichi Hirose, Atsushi Ogawa
Journal: Circulation (2018)

Introduction: Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown causes in childhood, causes coronary artery aneurysms (CAAs). Infliximab (IFX), anti-human TNF-α mo...
Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA
Authors: Qianwei Ye, Sunbin Ling, Shusen Zheng, Xiao Xu
Journal: Molecular Cancer (2019)

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of death worldwide. Due to latent liver disease, late diagnosis, and nonresponse to systemic treatments, surgical resection and/or biopsy specimens are still generally considered as the gold standard by clinicians for clinical decision-making until now. Since the conventional tissue biopsy is invasive and contains small tissue samples, it is unable to represent tumor heterogeneity or monitor dynamic tumor progression. Therefore, it is imperative to find a new less invasive or noninvasive diagnostic strategy to detect HCC at an early stage and to monitor HCC recurrence. Over the past years, a new diagnostic concept known as “liquid biopsy” has emerged with substantial attention. Liquid biopsy is noninvasive and allows repeated analyses to monitor tumor recurrence, metastasis or treatment responses in real time. With the advanced development of new molecular techniques, HCC circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) detection have achieved interesting and encouraging results. In this review, we focus on the clinical applications of CTCs and ctDNA as key components of liquid biopsy in HCC patients.
Abstract 19080: Association of Atrial Fibrillation Susceptibility Alleles and Intermediate Left Atrial and Pulmonary Vein Phenotypes and Their Impact on Catheter Ablation
Authors: Robert Schönbauer, Josephin Schmidl, Jedrzej Kosiuk, Lukas Fiedler, Laura Ueberham, Volker Adams, Borislav Dinov, Daniela Husser, Andreas Bollmann
Journal: Circulation (2012)

BACKGROUND: Recent genome-wide association studies have demonstrated that single-nucleotide polymorphisms (SNPs) on chromosomes 16q22 and 1q21 confer risk for atrial fibrillation (AF) but mechanisms and subsequent intermediate phenotypes remain elusive. Here, we analyzed the association between common AF susceptibility alleles and several left atrial and pulmonary vein phenotypes including left atrial and pulmonary vein dimensions and morphology and studied their impact on arrhythmia recurrence after AF ablation. METHODS: In 99 consecutive patients (mean age 61+/- 10 years, 68% male) undergoing catheter ablation for drug-refractory paroxysmal (48 %) or persistent (52 %) AF, left atrial and pulmonary vein dimensions were extracted from the preprocedural acquired multislice computed tomography (MSCT). Pulmonary vein anatomy was evaluated according to common trunk or additional veins. Left atrial voltage mapping was performed to identify scar and low voltage areas. Genotypes of rs7193343 (16q22) and rs13346333 (1q21) were determined. Serial 7-day Holter electrocardiographic recordings were acquired to detect AF recurrences. RESULTS: The presence of rs13346333 (1q21) was associated with a more spherical anatomy of the left atrium defined by the ratio of transversal to anterior-posterior diameter (OR: 0,138; 95% CI 0,022-0,856; p=0,033). In addition, rs7193343 (16q22) was associated with the presence of accessory veins (OR: 3,929; 95% CI 1,009-15,300; p=0,049). AF recurrence between 3 and 12 months occurred in 34,7 % of patients. Among the left atrial and pulmonary vein parameters, the presence of accessory pulmonary veins was associated with a significant lower risk of AF recurrence (OR: 0,587; 95% CI 0,461-0,748; p&lt;0,001). CONCLUSIONS: This study suggests an association between AF susceptibility alleles and anatomic variations of the left atrium and pulmonary veins. Accessory pulmonary veins are dominant AF triggers and their ablation leads to AF elimination.
Abstract 12551: Manifestation of J Waves in the General Population is Associated With Excessive Trabeculation Localized in the Left Ventricular Apex
Authors: Yoshiaki Kaneko, Koji Kurosawa, Tadashi Nakajima, Tadanobu Irie, Takashi Iizuka, Masahiko Kurabayashi
Journal: Circulation (2016)

Introduction: The presence of J wave in inferior and lateral ECG leads is a common finding in the general population, but the electrophysiological mechanism underlying the manifestation of the J wave remains unclear. Left ventricular (LV) trabeculation is frequently observed in healthy individuals, but its extent is highly variable among individuals. Hypothesis: Excessive LV trabeculation (ELVT) may be a cause of J wave in the general population. Methods: Of outpatients in our hospital for last 5 years who underwent 12-lead ECG and transthoracic echocardiography (TTE) simultaneously, we identified 148 patients who satisfied the following criteria: (1) no abnormalities on 12-lead ECG, (2) fair visualization of TTE especially in a short-axial view at the papillary muscle and an apical level, respectively, and in a long-axial apical view, and (3) no previous history of nor no echocardiographic evidence of heart diseases. We searched for ELVT, semi-quantitatively defined as the presence of noncompaction greater compaction. The study population was divided into 56 patients with J waves (56±17 year-old, 44 men. J-wave group), characterized by ≥0.1 mV notches or slurs of the terminal portion of the QRS complex, and 92 patients without (59±15 year-old, 39 men, control). Results: There was no significant difference in ECG parameters including RR, PQ, QRS width, QT and QTc between the two groups. In J-wave group, J wave with 0.2±0.1 mV, ranging between 0.1 and 0.5, was observed in the inferior leads in 51 patients, left precordial in 30 and high lateral in 10, and its morphology was slur in 36, notch in 11 and both in 9. ELVT was observed more frequently in J-wave group than control (28 patients (50%) versus 15 (16%), p&lt;0.01), but was distributed mainly in inferolateral wall of LV apex in both groups (inferior in 15 patients, lateral in 24, 1 in anterior and 1 in septal versus inferior in 1 and lateral in 15, p=0.04). No ELVT was detected at the papillary muscle level in both groups. Conclusions: These observations support our hypothesis that ELVT localized in the LV apex, probably carrying the Purkinje system deeper into the midmyocardium, might alter a propagation process in the terminal portion of QRS complexes, thus resulting in the manifestation of J waves in the general population.
Abstract 4282: Crosstalk between apoptosis and autophagy induced by docetaxel-magnetic nanoparticles with different surface in prostate cancer cells
Authors: Masatoshi Watanabe, Sanai Takahashi, Eri Usugi, Kenichiro Ishii, Yoshifumi Hirokawa
Journal: Cancer Research (2019)

Abstract Although docetaxel-based chemotherapy prolongs life and relieves symptoms in patients with castration resistant prostate cancer (CRPC), this needs to be improved because of limitations such as systemic toxicity, and progression of docetaxel-resistance. Nanotechnology including nanoparticles has served a new role in medical sciences, leading to theranostics. Fe3O4 magnetic nanoparticles (MgNPs) have potential applications in drug delivery, cancer diagnosis and hyperthermia. We have already reported that MgNPs would modify the effect of docetaxel (DTX) in prostate cancer cells by oxidative DNA damage in prostate cancer cell lines. Combined treatment of docetaxel and MgNPs has also shown to induce apoptosis and autophagic cell death in DU145 cells. In this study, we analyzed the combined effect of DTX-carboxyl-modified MgNPs (MgNPs-COOH) on DU145 cells in a view of crosstalk between apoptosis and autophagy. The combination treatment of DTX and MgNPs-COOH more effectively inhibited cancer cell growth and induced apoptosis and autophagic cell death although MgNPs-COOH did exert no ROS production. This combination preferred autophagic cell death than apoptosis. These results suggest that MgNPs-COOH may induce different responses compared with MgNPs, and result in favorable development of current chemotherapy for CRPC. Citation Format: Masatoshi Watanabe, Sanai Takahashi, Eri Usugi, Kenichiro Ishii, Yoshifumi Hirokawa. Crosstalk between apoptosis and autophagy induced by docetaxel-magnetic nanoparticles with different surface in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4282.
Abstract P367: Primordial Prevention of Coronary Heart Disease through Healthy Lifestyle in a Large Prospective Cohort of Young Women
Authors: Andrea K Chomistek, Stephanie E Chiuve, A. H Eliassen, Kenneth J Mukamal, Eric B Rimm
Journal: Circulation (2013)

Background: Although overall mortality rates from CHD in the U.S. have continued to decline in recent decades, the CHD mortality rate among women 35 to 54 years old has been increasing on average by 1.5% per year since 1997. This unfavorable trend may be explained, in part, by adverse lifestyle habits among younger adults. The purpose of this analysis was to estimate the burden of CHD among younger women that can be attributed to lack of adherence to a healthy lifestyle. Methods and Results: We conducted a prospective analysis among 93,161 women, 27-44 years of age at baseline, enrolled in the Nurses’ Health Study II cohort and followed from 1991 to 2009. Lifestyle factors were assessed repeatedly during follow-up by questionnaire. Healthy lifestyle was defined as not currently smoking, having a BMI of 18.5 [[Unable to Display Character: &amp;#8211;]] 24.9 kg/m 2 , engaging in at least 2.5 hours/week of moderate to vigorous-intensity physical activity, having a diet in the top 40% of Alternative Healthy Eating Index-2010, and consuming 5 [[Unable to Display Character: &amp;#8211;]] 30g/day of alcohol. To estimate the proportion of CHD that could be attributed to poor adherence to a healthy lifestyle, we calculated the population attributable risk percent. During follow-up, we documented 441 new cases of non-fatal MI and fatal CHD. After adjustment for other CVD risk factors, non-smoking, healthy BMI, exercise, and healthy diet were independently and significantly associated with lower CHD risk. Compared to women with 0 healthy lifestyle factors, the hazard ratio (HR) for CHD was 0.07 (95% CI, 0.03, 0.17) for women with all 5 healthy lifestyle factors (4% of the study population). Approximately 67% (95% CI 28%, 87%) of CHD cases in this population were attributable to poor adherence to a healthy lifestyle. Among non-smokers, 59% (95% CI 13%, 84%) of CHD cases were attributable to poor adherence to the other four healthy lifestyle factors. Conclusions: Primordial prevention through maintenance or adoption of a healthy lifestyle may lower incidence of CHD and potentially reverse the unfavorable trend in CHD mortality in younger women.
Abstract 226: Elucidating the Mechanism of Reduced Length-dependent Activation Due to a Dilated Cardiomyopathy-associated Mutation in Tropomyosin
Authors: Joseph D Powers, Farid Moussavi-Harami, Maria Razumova, Jil Tardiff, Michael Regnier
Journal: Circulation Research (2017)

At the subcellular level, the Frank-Starling law of the heart is described by an increase in calcium sensitivity and force with increased sarcomere length (SL). We examine how this relationship is affected by a dilated cardiomyopathy-associated mutation in tropomyosin (D230N, denoted Tm D230N ) by measuring contractility of intact and permeabilized cardiac muscle preparations at short (2.0 μm) and long (2.3 μm) SL. Transgenic mouse hearts containing the Tm D230N mutation have significantly dilated hearts and reduced cardiac output by ~6 months of age. Intact trabeculae were electrically stimulated and paced at 1 Hz with oxygenated solution (30°C) circulating through the experimental chamber, and permeabilized preparations were bathed in solutions (15°C) of progressively increased [Ca 2+ ] for measures of steady-state force. For intact muscle we found that the Tm D230N mutation results in significantly reduced twitch forces at SL 2.0 and 2.3 μm relative to wild-type (WT). Also, WT trabeculae displayed a significant increase in twitch force upon increase in SL (as expected) but Tm D230N trabeculae did not, demonstrating a loss of SL dependence of contraction. In permeabilized preparations, maximal activation (pCa 4.5) of both WT and Tm D230N preparations exhibited significant SL-dependent increases in force. However, at submaximal Ca 2+ (pCa 5.8), where the heart operates, WT preparations had significant increases in force with increasing length (comparing SL 2.0 to 2.3 μm), while this length-dependence of force augmentation in Tm D230N was absent. The increase in pCa 50 (pCa that produces half-maximal force) going from SL 2.0 to 2.3 μm was significantly less for Tm D230N preparations compared to WT, owing to a significantly smaller increase in pCa 50 at SL 2.3 μm (the pCa 50 at SL 2.0 μm was not significantly different between WT and Tm D230N ). These results suggest that the Tm D230N mutation limits an increase in the Ca 2+ sensitivity of contraction as the muscle lengthens by damping thin filament activation. To further examine length-dependent effects of the Tm D230N mutation, future experiments will test conditions that augment cross-bridge binding/inhibition, and other models of dilated cardiomyopathy that inhibit thin filament activation. Funding: HL111197
Thymic stromal lymphopoietin epigenetically upregulates Fc receptor γ subunit–related receptors on antigen-presenting cells and induces TH2/TH17 polarization through dectin-2
Authors: Yunsheng Liang, Bihui Yu, Junchen Chen, Haijin Wu, Yingping Xu, Bin Yang, Qianjin Lu
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 4940: The clinical significance of MRE11 expression based on location of primary tumor in colorectal cancer patients: an integrative analysis of multi-center data
Authors: Chuanwen Fan, Maria Kopsida, Youbin Liu, Hong Zhang, Jingfang Gao, Gunnar Arbman, Siyuwei Cao, Yuan Li, Zongguang Zhou, Xiaofeng Sun
Journal: Cancer Research (2019)

Abstract MRE11 plays an important role in DNA damage response for maintenance of genome stability and is becoming a prognostic marker. Its role, however, remains controversial in colorectal cancer (CRC) as it we don’t know if this difference is caused by the different locations of primary cancer. To figure out the prognostic heterogeneity of MRE11 in CRC, 207 primary CRC samples from Swedish, as well as 596 primary CRC samples from TCGA data were included in present study. The associations of MRE11 expression against tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with overall survival in right-sided CRC (RSCRC) and left-sided CRC (LSCRC) were assessed. The weighed gene co-expression network analysis and ClueGO were adopted to further analyze the different signaling of MRE11-related in RSCRC and LSCRC. The results showd that either high MRE11 expression alone (HR = 0.37, 95% CI = 0.18-0.76, P = 0.007) or the combination of high MRE11 expression with high TIICs was related to a favorable prognosis (HR = 0.150, 95% CI = 0.043-0.524, P = 0.003) in LSCRC. High MRE11 expression associated with a favorable prognosis in LSCRC with microsatellite stability (HR = 0.23, 95% CI = 0.09-0.55, P = 0.001). The relationships furnished above were adjusted for TNM stage, differentiation and/or TIICs, and no such evidence was present in RSCRC. Further analysis of the biological functions and the pathway involving MRE11 was associated with cell cycle process and DNA repair in both RSCRC (cor = 0.55, P = 0.55e-46) and LSCRC (cor = 0.62, P = 3e-64), whereas, activation of the immune response, necrotic cell death specifically correlated with LSCRC (cor = 0.5, P = 8e-38). In Conclusions, High MRE11 expression is associated with a favorable prognosis and the enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC. The prognostic heterogeneity of MRE11 in CRC may be due to the differential cell signals activated by MRE11 in RSCRC and LSCRC. The prognostic heterogeneity of MRE11 provides a novel rationale for stratifying patients accordingly, in order to obtain a better personalized prognostic evaluation for CRC patients. Citation Format: Chuanwen Fan, Maria Kopsida, Youbin Liu, Hong Zhang, Jingfang Gao, Gunnar Arbman, Siyuwei Cao, Yuan Li, Zongguang Zhou, Xiaofeng Sun. The clinical significance of MRE11 expression based on location of primary tumor in colorectal cancer patients: an integrative analysis of multi-center data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4940.