tbuckley/cabot-search huggingface dataset:
Abstract 1491: Expression of osteopontin splicing isoforms in childhood B-cell precursor acute lymphoblastic leukemia
Authors: Ana Clara Santos da Fonseca Bastos, Caroline Barbieri Blunck Blunck, Luciana Bueno Ferreira, Maria do Socorro Pombo-de-Oliveira, Mariana Emerenciano, Etel R. Gimba
Journal: Cancer Research (2018)

Abstract Osteopontin (OPN) suffers alternative splicing generating three OPN splicing isoforms (OPN-SI), named OPNa, OPNb and OPNc. However, OPN-SI roles in hematological malignancies (HMs) are still under investigation. Detection of specific gene rearrangements allows the identification of relevant prognostic subgroups of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Patients harbouring the ETV6-RUNX1 rearrangement are classified as a good prognostic subgroup, while those with the KMT2A-AFF1 fusion are included into poor prognostic subgroup. This work aimed to analyze the expression levels of OPN-SI in BCP-ALL cell lines and patient samples. We tested 4 BCP-ALL cell lines: 207, ALL-PO, RS4;11 and REH. Patient samples included 28 samples from patients harbouring the ETV6-RUNX1 fusion and 26 samples presenting the KMT2A-AFF1 rearrangement. We found that these three OPN-SIs are expressed in all BCP-ALL cell lines and in 70% of both patient prognostic subgroups tested. Both 207 and REH cell lines displayed higher OPNc and OPNb levels than OPNa. We found that OPNc is expressed in higher levels than OPNb and OPNa in unfavorable prognostic subgroup and is also overexpressed in relation to OPNc levels in relation to the ETV6-RUNX1 fusion the comparative subgroup. Interestingly, we found that higher OPNc transcriptional levels are associated with poor prognostic features, such as central nervous system (CNS), initial white blood cell counting and high risk of relapse. In conclusion, we found that the three tested OPN-SI are expressed in most tested BCP-ALL cell lines and BCP-ALL human samples. Since higher OPNc levels are associated to prognostic features, our data provide early evidence that these OPN-SIs could specifically contribute to step BCP-ALL progression. Further work should investigate their putative applications as additional risk-stratification and prognostic markers for BCP-ALL, as well as, their roles on modulating HM progression. Citation Format: Ana Clara Santos da Fonseca Bastos, Caroline Barbieri Blunck Blunck, Luciana Bueno Ferreira, Maria do Socorro Pombo-de-Oliveira, Mariana Emerenciano, Etel R. Gimba. Expression of osteopontin splicing isoforms in childhood B-cell precursor acute lymphoblastic leukemia [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 1491.
Mechanical Stretch Induces Enhanced Expression of Angiotensin II Receptor Subtypes in Neonatal Rat Cardiac Myocytes
Authors: KazuhisaKijima, HiroakiMatsubara, SatoshiMurasawa, KatsuyaMaruyama, YasukiyoMori, NaohikoOhkubo, IsseiKomuro, YoshioYazaki, ToshijiIwasaka, MitsuoInada
Journal: Circulation Research (1996)

Mechanical stress plays a pivotal role in the development of cardiac hypertrophy during hemodynamic overload, and angiotensin (Ang) II secreted from stretched myocytes plays an important role in mechanical stretch–induced hypertrophy. In the present study, we examined stretch-induced expression of Ang II receptors in an in vitro stretch model using 1-day-old rat myocytes. Both Ang II type 1 receptor (AT1-R) and type 2 receptor (AT2-R) mRNA levels were upregulated by myocyte stretching with similar time courses: significant increases were evident 6 hours after stretching, maximal levels (2.8- and 3.3-fold, respectively) were observed at 12 hours, and these were sustained for up to 18 hours. Ang II receptor expression in fibroblast-rich cultures was not affected by stretching. Conditioned medium in which myocytes were stretched for 12 hours significantly downregulated AT1-R and AT2-R mRNA levels in recipient myocytes, and this effect was almost completely blocked by AT1-R antagonists but not AT2-R antagonis...
Abstract 14052: Feasibility of Whole Genome Sequencing for Atrial Fibrillation
Authors: Steven Lubitz, Honghuang Lin, Lu-Chen Weng, Kathryn Lunetta, Carolina Roselli, Namrata Gupta, Stacey Gabriel, Goncalo Abecasis, Daniel MacArthur, Christine Albert, Alvaro Alonso, Dan Arking, Daniel Chasman, Vasan Ramachandran, Dan Roden, M. Benjamin Shoemaker, Susan Heckbert, Dawood Darbar, Emelia Benjamin, Patrick Ellinor
Journal: Circulation (2016)

Background: Genome-wide association studies (GWAS) have identified 14 loci associated with atrial fibrillation (AF). Whole genome sequencing (WGS) may enable the identification of causal variation ...
The Treatment of Recurrent Ventricular Tachycardia with Bilateral Cervico-Thoracic Sympathetic-Ganglionectomy
Authors: Richardlloyd, Robertokada, Jamesstagg, Robertanderson, Brackhattler, Frankmarcus
Journal: Circulation (1974)

Two patients had bilateral cervico-thoracic sympatho-ganglionectomy for treatment of disabling symptoms due to refractory ventricular tachycardia. In both patients treatment with antiarrhythmic drugs singly, in combination, or together with pacemaker overdrive had been ineffective in controlling this arrhythmia. Both patients had normal coronary arteriograms. Bilateral thoracic sympathectomy appears to facilitate medical management of ventricular tachycardia in selected patients who are refractory to the usual medical treatment.
Oxidized Albumin Triggers a Cytokine Storm in Leukocytes Through P38 Mitogen‐Activated Protein Kinase: Role in Systemic Inflammation in Decompensated Cirrhosis
Authors: José Alcaraz‐Quiles, Mireia Casulleras, Karl Oettl, Esther Titos, Roger Flores‐Costa, Marta Duran‐Güell, Cristina López‐Vicario, Marco Pavesi, Rudolf E. Stauber, Vicente Arroyo, Joan Clària
Journal: Hepatology (2018)

Decompensated cirrhosis is characterized by exuberant systemic inflammation. Although the inducers of this feature remain unknown, the presence of circulating forms of oxidized albumin, namely human nonmercaptalbumin 1 (HNA1) and HNA2, is a common finding in cirrhosis. The aim of this study was to explore the ability of these oxidized albumin forms to induce systemic inflammation by triggering the activation of peripheral leukocytes. We observed significantly higher plasma levels of HNA1 and HNA2 in patients with cirrhosis (n = 256) compared to healthy volunteers (n = 48), which gradually increased during the course from compensated to decompensated to acute‐on‐chronic liver failure. Plasma HNA1 and HNA2 levels significantly correlated with inflammatory markers (i.e., interleukin‐6 [IL‐6], IL‐1β, tumor necrosis factor‐alpha [TNF‐α] and IL‐8) in patients with cirrhosis. To directly test the inflammatory effects of HNA1 and HNA2 on leukocytes, these oxidized albumin forms were prepared ex vivo and their posttranslational modifications monitored by liquid chromatography (LC)–quadrupole time‐of‐flight/mass spectrometry (MS). HNA1, but not HNA2, increased IL‐1β, IL‐6, and TNF‐α mRNA and protein expression in leukocytes from both healthy volunteers and patients with cirrhosis. Moreover, HNA1 up‐regulated the expression of eicosanoid‐generating enzymes (i.e., cyclooxygenase‐2 [COX‐2] and microsomal prostaglandin E [PGE] synthase 1) and the production of inflammatory eicosanoids (PGE 2 , PGF 2α , thromboxane B 2 , and leukotriene B 4 ), as determined by LC–electrospray ionization–MS/MS. The inflammatory response to HNA1 was more pronounced in peripheral blood mononuclear cells (PBMCs) and marginal in polymorphonuclear neutrophils. Kinome analysis of PBMCs revealed that HNA1 induced the phosphorylation of p38 mitogen‐activated protein kinase, the inhibition of which blocked HNA1‐induced cytokine and COX‐2 induction. Conclusion: HNA1 triggers an inflammatory response in PBMCs, providing a rationale for its removal and replacement by reduced albumin in the prevention of systemic inflammation in patients with advanced liver disease.
Resection of gallbladder polyps following endoscopic ultrasound-guided cholecystoduodenostomy using a lumen-apposing metal stent
Authors: Li Tian, Yuanyuan Yang, Dinghua Xiao, Rui Wang, Xiayu Li, Shourong Shen, Xiaoyan Wang
Journal: Endoscopy (2018)

A 52-year-old woman with gallbladder polyps had a strong wish to keep her gallbladder. Abdominal ultrasound showed the contractile function of her gallbladder was good. Imaging including endoscopic ultrasound (EUS), computed tomography (CT), and abdominal ultrasound indicated that these polyps were benign lesions. Therefore, an EUS-guided gallbladder polyp resection was performed, instead of cholecystectomy ([Video 1]).
Abstract 699: Pd-l1 gene alterations identify a subset of diffuse large B cell lymphoma harboring a T cell inflamed phenotype
Authors: Justin Paul Kline, James Godfrey, Sravya Tumuluru, Girish Venkataraman, Riyue Bao, Sonali M. Smith
Journal: Cancer Research (2018)

Abstract Programmed death – ligand 1 (PD-L1) expression on malignant cells is a dominant immune escape mechanism across a variety of human cancers, and classically occurs as an adaptive response to the presence of activated T cells and interferon gamma (IFN-γ) in the tumor environment. Interestingly, a unique genetic mechanism underlying PD-L1 up-regulation has been described in classical Hodgkin lymphoma (cHL) and in uncommon variants of diffuse large B cell lymphoma (DLBCL), in which the chromosomal region (9p24.1) encoding the PD-1 ligands is highly amplified. While chromosome 9p24.1 copy number alterations (CNA) are ubiquitous in cHL, which is exquisitely sensitive to PD-1 blockade therapy, they also occur in DLBCL, albeit with a lower incidence. Here, FISH was utilized to identify DLBCLs harboring pd-l1 CNA, thereby enabling a characterization the immunogenomic landscape of these lymphomas compared to those lacking pd-l1 CNA. Among 76 DLBCLs analyzed, 25% harbored pd-l1 CNA (12 copy gain, 6 amplified, 1 translocation). Pd-l1 CNA were highly enriched among DLBCLs with an activated B cell (ABC) phenotype (75%). PD-L1 cell surface expression was strikingly enhanced in DLBCLs with pd-l1 CNA versus those without, as assessed by PD-L1 H score. Furthermore, pd-l1 CNA were associated with a pronounced infiltration of DLBCLs by T cells with a restricted T cell receptor (TCR) – beta (β) repertoire, suggesting that lymphoma antigen-specific T cells had expanded in these samples. RNA-sequencing of pd-l1 gene-altered versus non-altered DLBCLs revealed differential expression of pd-l1, as well as genes involved in T cell and cytokine signaling in the former, indicating that pd-l1 gene-amplified DLBCLs have been subjected to host immune surveillance. Lastly, whole exome sequencing (WES) of pd-l1 gene altered versus non-altered DLBCLs to identify potential differences in mutational loads and profiles is ongoing. Collectively, our results indicate that pd-l1 CNA identify a unique biological subset of DLBCL that has activated an endogenous anti-lymphoma immune response, and that may be more likely to respond to checkpoint blockade therapy with anti-PD-1 antibodies. We propose that a straightforward FISH analysis for pd-l1 gene amplification may be useful as a predictive biomarker for immunotherapy responsiveness in DLBCL. Citation Format: Justin Paul Kline, James Godfrey, Sravya Tumuluru, Girish Venkataraman, Riyue Bao, Sonali M. Smith. Pd-l1 gene alterations identify a subset of diffuse large B cell lymphoma harboring a T cell inflamed phenotype [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 699.
Abstract 15349: A Comparison of Clinical and Hemodynamic Characteristics of Pre- and Post-Tricuspid Congenital Shunts Resulting in Pulmonary Arterial Hypertension: Insights from a National Study
Authors: Cihangir Kaymaz, Serdar Kucukoglu, Gul Sagin Saylam, Dursun Alehan, Lale Tokgozoglu, Serdar Kula, Atif Akcevin, Alpay Celiker, Sertac Cicek, Birgul Varan
Journal: Circulation (2012)

Purpose: Post-tricuspid (postTri) congenital shunts have been considered to elicit an earlier progression to pulmonary arterial hypertension (PAH) than pre-tricuspid (preTri) defects. However, the ...
Conventional culture methods with commercially available media unveil the presence of novel culturable bacteria
Authors: Tamaki Ito, Tsuyoshi Sekizuka, Norimi Kishi, Akifumi Yamashita, Makoto Kuroda
Journal: Gut Microbes (2018)

Recent metagenomic analysis has revealed that our gut microbiota plays an important role in not only the maintenance of our health but also various diseases such as obesity, diabetes, inflammatory bowel disease, and allergy. However, most intestinal bacteria are considered 'unculturable' bacteria, and their functions remain unknown. Although culture-independent genomic approaches have enabled us to gain insight into their potential roles, culture-based approaches are still required to understand their characteristic features and phenotypes. To date, various culturing methods have been attempted to obtain these 'unculturable' bacteria, but most such methods require advanced techniques. Here, we have tried to isolate possible unculturable bacteria from a healthy Japanese individual by using commercially available media. A 16S rRNA (ribosomal RNA) gene metagenomic analysis revealed that each culture medium showed bacterial growth depending on its selective features and a possibility of the presence of novel bacterial species. Whole genome sequencing of these candidate strains suggested the isolation of 8 novel bacterial species classified in the Actinobacteria and Firmicutes phyla. Our approach indicates that a number of intestinal bacteria hitherto considered unculturable are potentially culturable and can be cultured on commercially available media. We have obtained novel gut bacteria from a healthy Japanese individual using a combination of comprehensive genomics and conventional culturing methods. We would expect that the discovery of such novel bacteria could illuminate pivotal roles for the gut microbiota in association with human health.
Troglitazone Inhibits Voltage-Dependent Calcium Currents in Guinea Pig Cardiac Myocytes
Authors: ToshiakiNakajima, KuniakiIwasawa, HitoshiOonuma, HiroyukiImuta, HisanoriHazama, MichikoAsano, ToshihiroMorita, FumitakaNakamura, Jun-ichiSuzuki, SeijiSuzuki, YasushiKawakami, MasaoOmata, YukichiOkuda
Journal: Circulation (1999)

Background—It has been suggested that intracellular Ca2+ overload in cardiac myocytes leads to the development of diabetic cardiomyopathy. Troglitazone, an insulin-sensitizing agent, is a promising therapeutic agent for diabetes and has been shown to prevent diabetes-induced myocardial changes. To elucidate the underlying mechanism of troglitazone action on cardiac myocytes, the effects of troglitazone on voltage-dependent Ca2+ currents were examined and compared with classic Ca2+ antagonists (verapamil and nifedipine). Methods and Results—Whole-cell voltage-clamp techniques were applied in single guinea pig atrial myocytes. Under control conditions with CsCl internal solution, the voltage-dependent Ca2+ currents consisted of both T-type (ICa,T) and L-type (ICa,L) Ca2+ currents. Troglitazone effectively reduced the amplitude of ICa,L in a concentration-dependent manner. Troglitazone also suppressed ICa,T, but the effect of troglitazone on ICa,T was less potent than that on ICa,L. The current-voltage relat...
Modulating Bone Marrow Hematopoietic Lineage Potential to Prevent Bone Metastasis in Breast Cancer
Authors: Jessalyn M. Ubellacker, Ninib Baryawno, Nicolas Severe, Molly J. DeCristo, Jaclyn Sceneay, John N. Hutchinson, Marie-Therese Haider, Catherine S. Rhee, Yuanbo Qin, Walter M. Gregory, Ana C. Garrido-Castro, Ingunn Holen, Janet E. Brown, Robert E. Coleman, David T. Scadden, Sandra S. McAllister
Journal: Cancer Research (2018)

The presence of disseminated tumor cells in breast cancer patient bone marrow aspirates predicts decreased recurrence-free survival. Although it is appreciated that physiologic, pathologic, and therapeutic conditions impact hematopoiesis, it remains unclear whether targeting hematopoiesis presents opportunities for limiting bone metastasis. Using preclinical breast cancer models, we discovered that marrow from mice treated with the bisphosphonate zoledronic acid (ZA) are metastasis-suppressive. Specifically, ZA modulated hematopoietic myeloid/osteoclast progenitor cell (M/OCP) lineage potential to activate metastasis-suppressive activity. Granulocyte-colony stimulating factor (G-CSF) promoted ZA resistance by redirecting M/OCP differentiation. We identified M/OCP and bone marrow transcriptional programs associated with metastasis suppression and ZA resistance. Analysis of patient blood samples taken at randomization revealed that women with high-plasma G-CSF experienced significantly worse outcome with adjuvant ZA than those with lower G-CSF levels. Our findings support discovery of therapeutic strategies to direct M/OCP lineage potential and biomarkers that stratify responses in patients at risk of recurrence.Significance: Bone marrow myeloid/osteoclast progenitor cell lineage potential has a profound impact on breast cancer bone metastasis and can be modulated by G-CSF and bone-targeting agents. Cancer Res; 78(18); 5300-14. ©2018 AACR.
Abstract 18045: Mild Coarctation of the Aorta: To Touch or Not to Touch the Patient? Looking at Left Ventricular Function and Hemodynamics
Authors: Zahra Keshavarz Motamed, Amanda Randles, Farhad Rikhtegar Nezami, Ramon Partida, Kenta Nakamura, Pedro V Staziaki, Brian Ghoshhajra, Ami Bhatt, Elazer R Edelman
Journal: Circulation (2015)

Introduction: Coarctation of the aorta (COA) is an obstruction of the aorta distal to the left subclavian artery. A peak-to-peak trans-coarctation pressure gradient (P K dP) of greater than 20 mmHg warns of severe COA and the need for interventional/surgical repair. The optimal method and timing of the intervention remain uncertain especially when the severity of COA is mild (P K dP &lt; 20 mmHg) and it is unclear if mild COA should be treated at all. Rosenthal (2001; J Am Coll Cardiol) suggested that treatment strategies for patients with mild COA may need to be redefined as transcatheter interventions emerge, and yet the risks and benefits of such interventions in patients with mild COA are unclear. The aim of this study is to investigate the effects of transcatheter intervention on hemodynamics of the aorta and left ventricle (LV) in eleven patients with mild COA. Methods. We used specially developed computational fluid dynamics and lumped parameter modeling framework along with highly-resolved particle image velocimetry data and clinical measurements (Doppler-echocardiography, cardiac catheterization, CT and MRI) in this study. Results . COA intervention can improve aortic hemodynamics to some extent (i.e., time-averaged wall shear stress, oscillating shear index, peak jet velocity and kinetic energy [all averaged in the descending aorta] were reduced by 20%, 13.3%, 26.7% and 25%, respectively). However there is no concomitant effect on the LV hemodynamics (i.e., stroke work, normalized stroke work and peak LV pressure were reduced by only 3.8%, 3.7% and 3.2%, respectively; arterial systemic compliance was also reduced by 17%; N=11; p &lt; 0.05). Conclusion . Our computational approach can effectively model and predict clinical conditions. Herein one must question intervention for mild COA, as it has limited utility in reducing myocardial strain. Figure 1. Catheter data and results of lumped parameter modeling in patient No. 1.
Abstract LB-125: Atovaquone suppresses triple negative breast tumor growth by inhibiting myeloid derived suppressor cells
Authors: Nehal Gupta, Stephen Wright, Sanjay Srivastava
Journal: Cancer Research (2018)

Abstract Triple negative breast cancer (TNBC) is considered to be the most aggressive and malignant neoplasm and is highly metastatic in nature. Metastatic TNBC is difficult to treat thus leading to extremely poor survival. The major contributing factor in TNBC progression and resistive nature is its ability to evade the immune surveillance. Modulating the immune system in breast tumors could be an important strategy for cancer therapeutics. The present study evaluates the immune response of atovaquone, an antiprotozoal drug in various TNBC cell lines and its efficacy in three independent in vivo models. In the first experiment, HCC1806 human breast cancer cells were orthotopically implanted in mammary fat of female mice. Oral administration of atovaquone reduced HCC1806 breast tumor growth by 45%. On the other hand, oral administration of atovaquone inhibited the growth of highly aggressive CI66 breast tumors by 70%. Paclitaxel is the first line chemotherapeutic agent for metastatic breast cancer. In third in vivo experiment, 4T1 paclitaxel resistant (4T1R) cells were injected in mice and atovaquone suppressed paclitaxel resistant tumor growth by 42%. Myeloid derived suppressor cells (MDSCs) are known to suppress immune function. Our current results demonstrated 70% and 30% suppression of tumor and blood MDSCs respectively, with atovaquone treatment in mouse bearing HCC1806 tumors. We also observed about 25% reduction in MDSCs with atovaquone treatment in mice with CI66 as well as 4T1R tumors. MDSCs induce regulatory T cells (Treg cells) which are immunosuppressive. Our results showed reduction of Treg cells by 12% and 17% with atovaquone treatment in HCC1806 tumors and in 4T1R tumors respectively. In addition, decrease in TGF-beta (13%) and IL-10 (40%) in HCC1806 tumor lysates was observed by atovaquone, an evidence of reduction in immunosuppressive cytokines produced by MDSCs. It appears that the mechanism of immune suppression of atovaquone by MDSCs in our model may be through TGF-β and IL-10, which are potent immunosuppressive cytokines and induce Treg cells that allow cancer cells to escape from immune surveillance. This is the first report demonstrating that immune modulation by atovaquone treatment is associated with breast tumor growth suppression, prompting further investigation to establish atovaquone as a treatment option for TNBC patients. Citation Format: Nehal Gupta, Stephen Wright, Sanjay Srivastava. Atovaquone suppresses triple negative breast tumor growth by inhibiting myeloid derived suppressor cells [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 LB-125.