tbuckley/cabot-search huggingface dataset:
Abstract 1639: Androgen receptor and ALDH1 expression among internationally diverse patient populations
Authors: Evelyn M. Jiagge, Aisha Jibri, Jessica Bensenhaver, Max Wicha, Baffour Awuah, Sofia Merajver, Lisa Newman
Journal: Cancer Research (2018)

Abstract Background: Population-based incidence rates of breast cancers that are negative for the estrogen receptor (ER), progesterone receptor (PR), HER2/neu triple-negative breast cancer (TNBC) are higher among African American (AA) compared to White American (WA) women, and several studies suggest that TNBC prevalence is increased among selected populations of African patients. The colonial-era transatlantic slave trade resulted in shared ancestry between contemporary AA and Gh populations. The extent to which associations between TNBC are related to East African versus West African ancestry, and whether these associations extend to expression of additional hormone receptors such as androgen receptor (AR) and stem cell markers such as ALDH1, is uncertain, but this research may explain breast cancer disparities between domestic communities within the United States as well as between international population subsets. Methods: We utilized immunohistochemistry to evaluate ER, PR, HER2/neu, AR and ALDH1 expression among White American (n=153), African American (n=76), Ethiopian (Eth)/East African (n=90), and Ghanaian (Gh)/West African (n=286) breast cancers through an IRB-approved international research program. Results: Mean age at breast cancer diagnosis was 43, 49, 60, and 57 years for the Eth, Gh, AA, and WA patients, respectively. Frequency of TNBC was significantly higher for the AA and Gh patients (41% and 54%, respectively) compared to the WA and Eth patients (23% and 15%, respectively; p&amp;lt;0.001). These associations were unchanged when limited to patients age 50 years and younger (47% and 49% for AA and Gh, respectively, versus 18% and 16% for WA and Eth, respectively; p&amp;lt;0.001). Frequency of ALDH1 positivity was also higher for the AA and Gh tumors (32% and 36%, respectively) compared to the WA and Eth tumors (23% and 17%, respectively; p=0.007). Significant differences were also observed for distribution of AR positivity, which was 71%, 55%, 42%, and 50% for the WA, AA, Gh, and Eth cases, respectively (p=0.008). Frequency of ALDH1 expression was numerically higher in the AA, Gh, and Eth TNBC cases compared to the WA TNBC cases, but this was not statistically significant (33%, 41%, and 31%, respectively, versus 18%; p=0.47). Conclusions: Extent of African ancestry appears to be associated with particular breast cancer phenotypes. West African ancestry correlates with increased risk of TNBC and breast cancers that are positive for ALDH1. Citation Format: Evelyn M. Jiagge, Aisha Jibri, Jessica Bensenhaver, Max Wicha, Baffour Awuah, Sofia Merajver, Lisa Newman. Androgen receptor and ALDH1 expression among internationally diverse patient populations [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 1639.
Contribution of Recirculation and Fat Diffusion to Myocardial Washout Curves Obtained by External Counting in Man
Authors: Attiliomaseri, Antoniopesola, Antoniol'abbate, Carlocontini, Claudiomichelassi, Tommasod'angelo
Journal: Circulation Research (1974)

133Xenon and 125I-iodoantipyrine (IAP) solutions were simultaneously injected into the left coronary artery in four normal patients and four patients with coronary artery obstructions. Recirculation was computed by convolution of the fractional decrease of the curve following inlet injection over a second curve obtained following right atrial injection. Uncorrected xenon and IAP curves were not statistically different in spite of the lower myocardium-blood partition coefficient and the recirculation of xenon. Corrected IAP curves could be followed down to 1.7%, whereas xenon curves could be followed only to 7.5%, indicating significant xenon diffusion holdup in fat. Corrected IAP curves deviated from a monoexponential course below 5% of peak in normal patients and at about 10% in patients with coronary artery obstructions. Stochastic analysis gave flow values 22% lower and 45% higher, respectively, than those computed from monoexponential extrapolation of corrected IAP and uncorrected xenon curves. With t...
Abstract 2025: CD147/EMMPRIN mediates epithelial-mesenchymal transition of head and neck squamous cell carcinoma
Authors: Shinsuke Suzuki
Journal: Cancer Research (2018)

Abstract Epithelial-mesenchymal transition (EMT) is a key mechanism in the progression of solid tumors. This process is characterized by the development of more migratory, invasive cell behavior. Transforming growth factor-β (TGF-β) has been well characterized as a potent inducer of EMT. CD147, also known as extracellular matrix metalloproteinase inducer (EMMPRIN), a member of the immunoglobulin superfamily, is highly expressed in cancer cells and induces malignant characteristics in various tumors, including head and neck squamous cell carcinoma (HNSCC). Accumulating evidence indicates a contribution of CD147/EMMPRIN to tumorigenesis of solid tumors. However, the function of CD147/EMMPRIN in EMT and TGF-β-induced tumorigenicity in HNSCC has not yet been explored. To determine the role of CD147/EMMPRIN in EMT and TGF-β-induced tumorigenic behavior, SAS, a tongue squamous cell carcinoma cell line, was stimulated with TGF-β. After stimulation with TGF-β, we found that SAS cells acquired a spindle-shaped morphology. Immunoblotting analysis showed that the expression of vimentin was upregulated and E-cadherin was downregulated after TGF-β treatment. This result suggests that EMT was induced by TGF-β in SAS cells. In addition, expression of CD147/EMMPRIN was upregulated in SAS cells using TGF-β treatment. TGF-β stimulation enhanced the migratory ability of the cells. Furthermore, the TGF-β-induced migratory ability, and the change in cellular morphology was diminished by CD147/EMMPRIN knockdown. These results suggest that CD147 is involved in TGF-β-induced EMT and the migratory capacity of HNSCC. Citation Format: Shinsuke Suzuki. CD147/EMMPRIN mediates epithelial-mesenchymal transition of head and neck squamous cell carcinoma [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 2025.
Endothelin Receptors in the Failing and Nonfailing Human Heart
Authors: KlausPönicke, MagdaleneVogelsang, MoritzHeinroth, KarinBecker, OliverZolk, MichaelBöhm, Hans-ReinhardZerkowski, Otto-ErichBrodde
Journal: Circulation (1998)

Background—In patients with chronic heart failure (CHF), plasma endothelin-1 (ET-1) levels are increased. We studied whether the cardiac ET-receptor system is altered in CHF patients. Methods and Results—We assessed ET-evoked inositol phosphate (IP) formation in slices from right atria and left ventricles from 6 potential heart transplant donors (NFH) and 15 patients with end-stage CHF; in membranes from the same tissues, we studied ET-induced inhibition of isoprenaline- and forskolin-stimulated adenylyl cyclase and ET-receptor density. ET (10−9 to 10−6 mol/L, ET-1 >>> ET-3) increased IP formation in right atria and left ventricles through ETA-receptor stimulation in a concentration-dependent manner; no difference in potency or efficacy between NFH and CHF hearts was observed. ET-1 (10−10 to 10−6 mol/L), via ETA-receptor stimulation, inhibited isoprenaline- and forskolin-stimulated adenylyl cyclase in right atria but not in left ventricles, whereas carbachol inhibited adenylyl cyclase in both tissues; aga...
Long-Term Clinical and Echocardiographic Follow-Up After Percutaneous Mitral Valvuloplasty With the Inoue Balloon
Authors: RosaHernandez, CaminoBañuelos, FernandoAlfonso, JavierGoicolea, AntonioFernández-Ortiz, JavierEscaned, LuisAzcona, CarlosAlmeria, CarlosMacaya
Journal: Circulation (1999)

Background—The objective of this study was to assess the long-term clinical outcome and valvular changes (area and regurgitation) after percutaneous mitral valvuloplasty (PMV). Methods and Results—After PMV, 561 patients were followed up for 39 (±23) months and clinical/echocardiographic data obtained yearly. Kaplan-Meier and Cox regression analyses were performed to estimate event-free survival, its predictors, and the relative risks of several patient subgroups. There were several nonexclusive events: 19 (3.3%) cardiac deaths, 55 (9.8%) mitral replacements, 6 (1%) repeated PMVs, 56 (10%) cases of restenosis, and 108 (19%) cases of clinical impairment. Survival free of major events (cardiac death, mitral surgery, repeat PMV, or functional impairment) was 69% at 7 years, ranging from 88% to 40% in different subgroups of patients. Wilkins score was the best preprocedural predictor of mitral opening, but the procedural result (mitral area and regurgitation) was the only independent predictor of major event-...
Abstract 15274: Aspirin Protects Heart Against Ischemia-Reperfusion Injury via LKB1-Sestrn2-AMPK Signaling Cascade
Authors: Yanping Bi, Chelsea Luckett, Shaoxin Lu, Ji Li
Journal: Circulation (2017)

Introduction: AMP-activated protein kinase (AMPK) is a stress signaling enzyme that orchestrates the regulation of energy pathways. Intrinsic AMPK activation protects the heart against ischemic injury, but whether the pharmacologic AMPK stimulation by aspirin mitigates ischemia-reperfusion damage is unknown. Hypothesis: Aspirin as an emerging AMPK agonist could stimulate the cardiac AMPK signaling pathway that attenuates myocardial ischemia-reperfusion injury. Methods: The cardioprotective activity of aspirin was evaluated in an in vivo regional ischemia/reperfusion (45 min/24 hours) injury model in which the left anterior descending coronary artery (LAD) was occluded and released. The Langendroff perfused heart system was used to approach an ex vivo global ischemia and reperfusion model. Results: Isolated mouse hearts ex vivo pre-treated with aspirin had better recovery of left ventricular contractile function (55% vs. 29% of baseline heart rate-pressure product; p<0.05) and less myocardial necrosis (56%...
Abstract 782: Development of a high throughput in vitro screening platform to identify novel inducers of immunological cell death
Authors: Didier Grillot, Akanksha Gangar, Raphaelle Guillard-Huet, Eric Boursier, Florent Potvain, Guillaume Serin, Jean-François Mirjolet
Journal: Cancer Research (2018)

Abstract Immunological cell death (ICD) is a form of cancer cell death induced by radiotherapy, photodynamic therapy and a few chemotherapeutic agents such as Doxorubicin, Mitoxantrone, and Oxaliplatin. Unlike apoptosis or necrosis, ICD can induce an effective immune response directed against the tumor whereby both dendritic cells and T lymphocytes are mediators of this response. Dying cancer cells recruit and activate immune cells by releasing damage-associated molecular patterns (DAMPS) that help and promote the immune response to antigenic tumor neo-epitopes. Three key DAMPS are associated with the ICD process: calreticulin exposition on the cell surface, ATP secretion and high-mobility group box 1 (HMGB1) release. In order to identify new therapeutic agents that promote ICD in malignant cells, we developed a screening strategy facilitated by an automated in vitro platform with four assays on three different tumor cell lines (human osteosarcoma U-2 OS, human breast MDA-MB-231 and murine liver Hepa 1-6). ICD inducers Doxorubicin and Mitoxantrone used as positive controls increased ATP secretion by 2 to 10-fold at a non-cytotoxic dose after 72 hours incubation on the three cell lines. Both compounds also increased calreticulin exposition by 2 to 4-fold (determined by immunofluorescence using the Operetta High-Content Imaging System) and HMGB1 release by two-fold on the three cell lines. Here we will present recent data from the screening of Oncodesign's Nanocyclix® library using this platform to identify novel ICD inducers. Citation Format: Didier Grillot, Akanksha Gangar, Raphaelle Guillard-Huet, Eric Boursier, Florent Potvain, Guillaume Serin, Jean-François Mirjolet. Development of a high throughput in vitro screening platform to identify novel inducers of immunological cell death [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 782.
Abstract 18280: Mucociliary Clearance Deficit and Reduced Pulmonary Function in Congenital Heart Disease Infants Undergoing Surgery With Cardiopulmonary Bypass
Authors: Phillip S Adams, Timothy E Corcoran, Daniel J Weiner, Maliha Zahid, Al Saville, Stephen A Walczak, Omar Khalifa, Michael S Czachowski, Yuliya Domnina, Mahesh S Sharma, Brian Blasiole, Patrick M Callahan, Ivy Lin, Joan Sanchez-de-Toledo, Cecilia W Lo
Journal: Circulation (2016)

Introduction: Postoperative pulmonary complications are common after congenital cardiac surgery requiring cardiopulmonary bypass (CPB). Given our previous finding of a high prevalence of airway cil...
Abstract 1434: LSR promotes lipid metabolism via beta oxidation and contributes cell viability in epithelial ovarian cancer
Authors: Kosuke Hiramatsu, Satoshi Serada, Minoru Fujimoto, Shinya Matsuzaki, Yutaka Ueda, Kiyoshi Yoshino, Tadashi Kimura, Tetsuji Naka
Journal: Cancer Research (2018)

Abstract Background:Previously, we identified lipolysis-stimulated lipoprotein receptor (LSR) as a new target of epithelial ovarian cancer (EOC), and we reported inhibitory effect of our newly developed monoclonal antibody (mAb) against LSR-positive ovarian cancer cells in vitro and in vivo. We also demonstrated that LSR took in triglyceride-rich protein and promoted cell proliferation, however, LSR function in EOC cells is not investigated enough. Therefore, we aimed to reveal the function of LSR in EOC cells focusing on lipid metabolism including beta oxidation and subsequent TCA cycle. Material and Method: Using LSR-positive ovarian cancer cell lines (OVCAR3 and RMG-I), we investigated activation of beta-oxidation by LSR after administration of VLDL which is one of the triglyceride-rich protein. Moreover, we constructed LSR-knockdown EOC cells and investigated the effect of VLDL administration in these cells. In addition, we showed inhibitory effect of our anti-LSR mAb against lipid metabolism. Expression of beta-oxidation related proteins were analyzed by western blot analysis. Production of acetyl CoA and ATP were measured using each assay kit. Cell viability was analyzed by WST-8 assay and thymidine incorporation assay. Results: In LSR-positive EOC cells, LSR promoted uptake of VLDL in glucose restricted environment compared with LSR-knockdown cells (p &amp;lt; 0.05) and VLDL administration promoted acetyl CoA and ATP production (p &amp;lt; 0.05), suggesting that beta-oxidation, TCA cycle and electron transport system were activated by fatty acid from VLDL in LSR-positive cells. Moreover, in LSR-positive EOC cells, VLDL administration increased viable cells compared with LSR-knockdown cells (p &amp;lt; 0.05), however, DNA synthesis was not promoted (p &amp;lt; 0.05). These results showed that VLDL uptake via LSR promoted lipid metabolism and contributed cell viability. Finally, our anti-LSR mAb inhibited these processes. Conclusion: In glucose restricted environment, LSR takes in triglyceride-rich protein, activates lipid metabolism via beta-oxidation and contributes cell viability in LSR-positive EOC cells. Citation Format: Kosuke Hiramatsu, Satoshi Serada, Minoru Fujimoto, Shinya Matsuzaki, Yutaka Ueda, Kiyoshi Yoshino, Tadashi Kimura, Tetsuji Naka. LSR promotes lipid metabolism via beta oxidation and contributes cell viability in epithelial 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 1434.
An open-label phase 1b study of obinutuzumab plus lenalidomide in relapsed/refractory follicular B-cell lymphoma
Authors: Franck Morschhauser, Gilles Salles, Steven Le Gouill, Herve Tilly, Catherine Thieblemont, Krimo Bouabdallah, Bettina Fabiani, Cédric Ménard, Karin Tarte, Guillaume Cartron, Roch Houot
Journal: Blood (2018)
Abstract 92: Sirtuin 2 mediated-deacetylation regulates cellular iron homeostasis
Authors: XiaoyanYang, AthanassiosVassilopoulos, Seong-HoonPark, DavidGius, HosseinArdehali
Journal: Circulation Research (2014)

Background: Sirtuins (SIRTs) are NAD+-dependent deacetylases, which regulate energy metabolism and response to oxidative stress in the heart. Iron is essential for these processes but is toxic when present in excess. However, whether SIRTs are involved in maintaining cellular iron homeostasis is not known. SIRT2 is among the least characterized SIRTs and is mainly present in the cytoplasm. We hypothesized that SIRT2 is required for cellular iron homeostasis. Methods and Results: Iron content was significantly lower in SIRT2-/- mouse embryonic fibroblasts (MEFs) compared to SIRT2+/+ MEFs (non-heme iron: 0.073 vs. 0.060 nmol/μg protein, p=0.02), andlevels of ferroportin-1 (FPN1), the major cellular iron exporter, was significantly increased in SIRT2-/- MEFs. Similarly, silencing SIRT2 in HepG2 cells decreased cellular iron levels and increased FPN1 expression, indicating that enhanced FPN1 with SIRT2 downregulation drove iron export and caused a reduction in cellular iron levels. Furthermore, iron export as...
Abstract 16804: Tideglusib, a Novel Allosteric Inhibitor of Glycogen Synthase Kinase-3-β Mimics Canonical Wnt Signaling
Authors: JugajyotiBaruah, KishoreWary
Journal: Circulation (2014)

Rationale: As Glycogen Synthase Kinase-3 (GSK-3)β enzyme regulates β-catenin stability, we addressed the ability of Tideglusib, a novel allosteric inhibitor of GSK-3β, to activate canonical Wnt signaling in microvascular endothelial cells (ECs). Methods and Results: The treatment of primary ECs with Wnt3a or Tideglusib stabilized β-catenin polypeptide species in a dose-dependent manner. A time-course analyses showed increased in phosphorylated form of GSK-3β-S9, thereby, increased stabilization of β-catenin within 3-4 hours in response to Tideglusib. The addition of Tideglusib induced robust expression of not only transcription factor Nanog, but also Cyclin-D1 and Vascular Endothelial Growth Factor Receptor-2 proteins. Microscopic analyses demonstrated disappearance of VE-cadherin from the adherens junctions, while increased accumulation of β-catenin in the nucleus. Moreover, Fluorescence-activated cell sorting (FACS) of Propidium iodide and Annexin-V labeled ECs previously treated with Tideglusib showed ...
Abstract 4295: ASF1B promotes cell proliferation and regulates cell cycle in human benign prostate hyperplasia (BPH)
Authors: Nisha Dahiya Rani, Dr. Murali Ankem, Dr. Chendil Damodaran
Journal: Cancer Research (2018)

Abstract Background Benign Prostate Hyperplasia (BPH) is enlargement of the prostate, which occurs in 50% men above 50 years of age. Alpha-adrenergic blockers and 5-alpha-reductase inhibitors are the standard medical therapy for BPH. However, these treatments are not only partially effective but also cause significant toxicity in patients. Understanding the molecular pathogenesis of BPH may reveal novel preventive or therapeutic targets for BPH. Methods Normal Human Prostate Epithelial Cells (HPrEpC), RWPE-1 and Benign Prostate Hyperplasia (BPH) were utilized for global sequencing and molecular studies. Western blot analysis was performed to determine the expression of G0/G1 and S-phase and M phase regulators of the cell cycle in BPH and RWPE-1 lysates. Cell cycle and western blot analysis was performed at successive time-points post starvation to understand the dynamics of cell cycle progression in both the cell lines. Knock out experiments were conducted to understand the function ASF1B in normal and BPH cells. Results RNA sequencing analysis revealed that the level of ASF1b (Anti-Silencing Function 1B Histone Chaperone) was over 80 times upregulated in BPH cells as compared to healthy prostate epithelial cells. Induction of ASF1B is specific to BPH as confirmed at protein levels. Induction of ASF1B expression correlated in a time-dependent manner with the increased expression of G1 (cdk4, 6 and cyclin D), G1-S (cdk2) and S-phase (cdk2 and cyclin-A) regulators at both transcription and translation levels. The G1-S phase transcriptional enhancers such as E2-F1 were also upregulated with successive time-points. The cell cycle analysis at sequential time-points revealed that the BPH cells entry to S phase was achieved earlier and by higher fraction of cells than the healthy prostate epithelial cells. Knocking down ASF1B expression by siRNA inhibited the proliferation of BPH cells by 30%. The findings so far suggest that ASF1B might be related to hyper-proliferation in BPH cells. The results indicate that ASF1B might be a novel therapeutic target for preventing hyper-proliferation in BPH. Studies are ongoing to validate the expression of ASF1B in clinical samples along with screening of small molecules targeting ASF1B expression specifically. Current study may lead to identification of a novel preventive and/or therapeutic target and related treatment for BPH. Conclusion Our studies suggest that ASF1b is a G1 and S phase regulator which are critical phases for hyper-proliferative BPH cells. Citation Format: Nisha Dahiya Rani, Dr. Murali Ankem, Dr. Chendil Damodaran. ASF1B promotes cell proliferation and regulates cell cycle in human benign prostate hyperplasia (BPH) [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 4295.