tbuckley/cabot-search huggingface dataset:
Abstract 2085: Reactive oxygen species promote signaling in neuroblastoma cells
Authors: Dominick Harrison, Ruth Joanis, Cynthia M. van Golen
Journal: Cancer Research (2011)

Abstract Neuroblastoma is a rare cancer of the sympathetic nervous system that is commonly diagnosed in children before the age of five. Neuroblastoma affects 1 out of 100,000 children and about 700 new cases of neuroblastoma each year. Most cases of neuroblastoma begin in the abdomen in the adrenal gland, or next to spinal cord and in the chest. Neuroblastoma is known to spread to the bones, face, skull, pelvis, shoulder, arms, legs, bone marrow, liver, lymph nodes, skin and around the eyes. Currently, there is no explanation for the cause of neuroblastoma. Our lab seeks to understand the mechanisms used for these cells to metastasize. The Erk pathway, part of the mitogen activated protein kinases, helps to regulate the cell cycle, proliferation, invasion and metastasis. The PI3k/Akt pathway regulates cell growth, survival, and activation of transcription factors such as hypoxia inducible factors (HIFs). Hypoxia is a state where the cell is experiencing a lower than normal oxygen tension activating HIF-1 alpha and HIF-2 to cause an expression of target genes for angiogenesis, (generation of new blood cells), erythropoiesis (formation of new blood cells), and glucose transport into cells enabling them to survive under hypoxic conditions and acquire access to an oxygen supply. Hypoxia increases reactive oxygen species used to stabilize HIF-1 alpha. Reactive oxygen species generation is dependent on oxygen induced changes in the redox state of the electron transport chain. Low levels of reactive oxygen species can regulate controlled proliferation. However, high levels of reactive oxygen species lead to DNA damage and genomic instability by activating these signaling pathways stopping cell death in senescence leading to uncontrolled proliferation. Therefore, our hypothesis is that low levels of reactive oxygen species promote neuroblastoma cell survival through upregulation of survival signaling, whereas high levels of reactive oxygen species induce neuroblastoma cell apoptosis. To test this idea, we exposed an aggressive, metastatic cell lines, IMR 32 neuroblastoma cells, to increasing concentrations of hydrogen peroxide, used to induce reactive oxygen species formation. Cells were analyzed morphologically for apoptosis. With increasing concentrations of hydrogen peroxide, IMR32 neuroblastoma cells round up and become less adherent. High doses of hydrogen peroxide induce cell fragmentation indicative of apoptosis. We are currently investigating the effect of hydrogen peroxide on the induction of caspase-3, a proapoptotic molecule, and DNA fragmentation, measured by TUNEL assay. Our data suggest that reactive oxygen species induce apoptosis in human neuroblastoma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2085. doi:10.1158/1538-7445.AM2011-2085
Abstract 2735: Effects of metformin on a non-small cell lung cancer cell line with an EGFR mutation
Authors: Satoru Kitazono, Yuichi Takiguchi, Hironori Ashinuma, Miyako Kitazono, Atsushi Kitamura, Yuji Tada, Katushi Kurosu, Emiko Sakaida, Ikuo Sekine, Koichiro Tatsumi
Journal: Cancer Research (2012)

Abstract Background:Metformin, one of the most widely prescribed oral agents for treating diabetes mellitus, has been speculated to have antineoplastic effects. The effects, however, have not been fully understood. Experimental Design:A human non-small-cell lung cancer cell line, PC9 (with an EGFR mutation of the exon 19 E746-A750 deletion), was used to evaluate antineoplastic effects of metformin in vitro and in vivo. For in vitro experiments, the cells were exposed to metformin, gefitinib or cisplatin to observe inhibitory effects on cell proliferation. At 24, 48 and 72 hours after the start of the culture with the agents, cell cycle analysis, measurements of caspase 3, 8 and 9 activities, and evaluation with Hoechst staining and APOPercentage TM assay, respectively, were performed. For in vivo experiments in SCID mouse with a xenograft subcutaneous tumor, gefitinib (150 mg/kg, oral gavage) or metformin (250 mg/kg, i.p.) was daily administered to the mice. Results:Gefitinib at a concentration of 0.03 μM, cisplatin of 1.5 μg/ml and metformin of 10 mM exerted equivalent inhibitory effects on cell proliferation in vitro. At these particular concentrations, metformin did not induce significant apoptosis over control as assessed by Hoechst staining, APOPercent assay and caspase 3 activity, whereas gefitinib and cisplatin did induce apoptosis dramatically. Metformin failed to alter cell cycle distribution, whereas gefitinib and cisplatin caused G1/G0 an S phase accumulation, respectively. Metformin did not inhibit growth of already grown subcutaneous tumors, whereas the tumors shrank dramatically with gefitinib treatment. After almost complete disappearance of the tumors by gefitinib, however, they regrew by gefitinib withdrawal. Metformin did significantly suppress the regrowth of the tumors after gefitinib withdrawal. Conclusions: Metformin has inhibitory effects on growth of a human non-small cell lung cancer cell line with a sensitive EGFR mutation in vitro and in vivo, and its mechanism may not depend on apoptosis or cell cycle alteration. Although the agent does not suppress growth of already grown tumors, it significantly suppresses tumor regrowth after gefitinib withdrawal. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2735. doi:1538-7445.AM2012-2735
Visualization of the Kidneys on Xe-133 Ventilation Images of a Ventilation–Perfusion Scan
Authors: RADHIKA G. GUPTA, BRUCE BARRON, LAMK K. LAMKI
Journal: Clinical Nuclear Medicine (2001)

From the Division of Nuclear Medicine, Department of Radiology, University of Texas–Houston Medical School, Houston, Texas Received for publication February 14, 2001. Accepted April 4, 2001. Reprint requests: Bruce Barron, Division of Nuclear Medicine, Department of Radiology, University of Texas–Houston Medical School, 6431 Fannin, Suite 2132, Houston, Texas 77030. E-mail: [email protected]
The $640 Billion Question — Why Does Cost-Effective Care Diffuse So Slowly?
Authors: Victor R. Fuchs, Arnold Milstein
Journal: New England Journal of Medicine (2011)

Some U.S. health care organizations deliver high-quality care at a cost 20% below average. Why don't their models diffuse rapidly, as cost-effective approaches do in other industries? The answers lie in perceptions and behaviors of health care's major participants.
Effect of Chlorpromazine Hydrochloride on Carcinogen-Metabolizing Enzymes: Liver Microsomal Dimethylnitrosamine Demethylase, 4-Dimethylaminoazobenzene Reductase, and Aryl Hydrocarbon Hydroxylase&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Mostafa Hassan Mostafa, Elizabeth K. Weisburger
 6
Journal: JNCI Journal of the National Cancer Institute (1980)

Investigation of the effect of chlorpromazine hydrochloride (CPZ) on some enzymes involved in the metabolism of the carcinogens 4-dimethylaminoazobenzene (DAB), benzo[a]pyrene, and dimethylnitrosamine (DMN) revealed that CPZ inhibited hepatic microsomal DAB reductase, aryl hydrocarbon hydroxylase, and DMN demethylase II but markedly activated DMN demethylase I. Inhibition of these enzymes in vitro was proportional to the concentrations of CPZ. The effect of CPZ on DMN demethylase also depended on the concentrations of DMN and CPZ in the incubation mixture. Mechanisms to account for the inhibition of DAB reductase were suggested. Aryl hydrocarbon hydroxylase and DMN demethylase II activities of the 100,000×g hepatic microsomal fraction were activated by 33 and 61%, respectively, over the control values after a single injection of CPZ into F344 rats, but no effect on DAB reductase and DMN demethylase I activities was observed. Microsomal concentrations of protein and cytochrome P450 were not appreciably altered by CPZ treatment, whereas the level of microsomal NADPH cytochrome c reductase was slightly increased over control values. A similar effect on the drug-metabolizing enzymes was found during pretreatment of rats with CPZ for 5 days, except that the NADPH cytochrome c reductase was increased by 33% over the control values.
Analysis of the effect of body weight on the efficacy and safety of epoetin alfa
Authors: E. Vercammen, H. Ludwig, K. Liu, L. Xiu, P. Bowers
Journal: Journal of Clinical Oncology (2005)

8184 Background: Epoetin alfa for cancer-associated anemia is effective given as a weight-based dose (WBD; 150 IU/kg) or fixed dose (FD; 10,000 IU) 3-times weekly (TIW), or a FD (40,000 IU) once weekly (QW). Methods: To evaluate the effect of body weight on efficacy of FD vs WBD epoetin alfa, data from a FD trial (40,000 IU QW increased to 60,000 IU QW for insufficient response; N = 2964; Gabrilove 2004) and data from 8 WBD studies (150 IU/kg TIW increased to 300 IU/kg for insufficient response; N = 944) were analyzed and compared. Body weights were defined by quartiles (Q) derived from the European Cancer Anaemia Survey (Ludwig 2004). Efficacy endpoints were erythropoietic response (ER; hemoglobin [Hb] increase ≥2 g/dL) and Hb change from baseline. Safety was evaluated across weight categories in the FD trial. Results: Heavier patients (Q4; >79.5 kg) in the FD group had significantly (P=.0182) lower ER than lighter patients (Q1; ≤60.3 kg), 61% vs 66%, respectively. In the WBD group ER for heavier- vs lighter-weight patients was 63% vs 76%, respectively (P=.0779). Difference in effect of body weight on ER between the dosing regimens was not significant (P=.3005). FD epoetin alfa was effective in 58% of patients >95.9 kg. Heavier patients had slightly less Hb increase from baseline with the FD (2.0 g/dL Q1, 1.8 g/dL Q4; NS) and WBD (2.3 g/dL Q1, 1.9 g/dL Q4; NS). Even for patients who weighed ≥95.9 kg, mean Hb change was >1.5 g/dL. Probability of dose increase with the FD was 28% in Q1 and 42% in Q4 (P<.0001) indicating that heavier patients were more likely to receive a dose increase, as suggested by the lower ER. Differences in dose increases with WBD were not significant, ranging between 25% and 35%. Safety of FD epoetin alfa was similar across all body-weight quartiles indicating that safety was not compromised in lower-weight patients. Conclusion: Epoetin alfa administered as a FD is effective, even in patients >95 kg, but WBD may be preferable in heavier weight patients. Tolerance is excellent regardless of body weight. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson Ortho-Biotech
EFFECTS OF INTRAVENOUS IRON THERAPY IN IRON DEFICIENT PATIENTS WITH SYSTOLIC HEART FAILURE: META-ANALYSIS OF RANDOMIZED CONTROL TRIALS
Authors: Ewa Anita Jankowska, Tomasz Suchocki, Michal Tkaczyszyn, Stephan Von Haehling, Wolfram Doehner, Waldemer Banasiak, Stefan Anker, Piotr Ponikowski
Journal: Journal of the American College of Cardiology (2015)
SAT0207 Correlation of clinical, serologic and histologic findings in a large cohort of primary sjögren’s syndrome patients: A multicentric cross-sectional study:
Authors: C. Baldini, P. Pepe, L. Quartuccio, R. Priori, E. Bartoloni Bocci, A. Alunno, S. Colafrancesco, A. Gattamelata, M. Maset, M. Modesti, A. Tavoni, S. De Vita, R. Gerli, G. Valesini, S. Bombardieri
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although primary Sjögren's syndrome (pSS) is often a benign condition some patients develop systemic features. Identifying independent risk factors for pSS different clinical phenotypes would provide useful insights into patients' assessment. <h3>Objectives</h3> to describe the clinical presentation of pSS in a large cohort of patients and to identify independent risk factors for severe disease manifestations. <h3>Methods</h3> Cumulative demographic, clinical, serological, histological and therapeutic data of 1115 pSS patients were retrospectively evaluated. Independent risk factors for disease manifestations were identified by logistic regression. <h3>Results</h3> The cohort included 1115 (1067 F:48M) pSS patients with a mean age of 51.6±13.8 yrs at diagnosis and 57.5±13.7 yrs at inclusion in the study (mean follow-up=5.8±6.5 yrs). Anti-Ro/SSA and anti-La SSB were detected in the 68% and 37% of the cases. Xerostomia (92%), xerophtalmia (94%) and articular involvement (61%) were the most commonly detected clinical manifestations. Salivary gland enlargement was detected in 346/1115 (31%) pSS patients while 475/1115 (42%) developed systemic extra-glandular involvement. Moderate to severe leukopenia (28%), peripheral arthritis (11%) and sensory-motor neuropathy (1.8%) were the most severe disease extra-glandular manifestations requiring immunosuppressive drugs. Independent risk factors for leukopenia were Raynaud's phenomenon (RP) (p=0.008), low C3 (p=0.001), hypergammaglobulinemia (p=0.0006) and cryoglobulinemia (p=0.01). Arthritis was associated to RP (p=0.005) while sensory-motor neuropathy to purpura (p&lt;0.0001), low C4 (p&lt;0.0001) and cryoglobulinemia (p&lt;0.0001). From the analysis, low C3/C4, hypergammaglobulinemia and cryoglobulinemia emerged as prognostic adverse laboratory abnormalities. Table 1 summarises patients' clinical presentation according to the number of the laboratory abnormalities detected ("group A" = no abnormalities, "group B" =1 and "group C" ≥2 abnormalities). <h3>Conclusions</h3> This study described the presentation of pSS in a large cohort of patients allowing us to identify independent risk factors which might help to predict the signs and symptoms of the disease. Patients with laboratory signs of B-cell hyperactivation should be more closely monitored since they may be at higher risk of severe extra-glandular involvement. <h3>Disclosure of Interest</h3> None Declared
CHARACTERISTICS OF MYOCARDIAL BRIDGING EVALUATED BY CARDIAC COMPUTED TOMOGRAPHY ANGIOGRAPHY AND PRESENCE OF MYOCARDIAL ISCHEMIA BY SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY
Authors: Franklyn Agustin Colón Arias, Moises Jimenez-Santos, Francisco Castillo, Javier Moreno Rodriguez, Luis Azpeitia, Salvador Hernandez, Erick Alexanderson Rosas, Sergio Criales, Mariana Diaz Zamudio
Journal: Journal of the American College of Cardiology (2015)
COMPOUND HETEROZYGOSITY AFFECTS PHENOTYPES IN HYPERTROPHIC CARDIOMYOPATHY WITH MYBPC3 MUTATIONS: EVIDENCE FROM ZEBRAFISH MODELS
Authors: Akihiko Hodatsu, Tetsuo Konno, Kenshi Hayashi, Kenshi Hayashi, Yoji Nagata, Ryota Teramoto, Noboru Fujino, Masa-aki Kawashiri, Masakazu Yamagishi
Journal: Journal of the American College of Cardiology (2015)
A4.05 SMOC2, a secreted calcium-binding protein from cartilage extracellular matrix is an inhibitor of cartilage and bone formation
Authors: T Peeters, F Cailotto, RJ Lories
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> SMOC2, a secreted calcium-binding protein of the BM-40/SPARC family was identified from a chondrogenic extract of articular cartilage and is increased in osteoarthritic cartilage. We evaluated the impact of SMOC2 on <i>in vitro&nbsp;</i>chondrogenesis and on <i>in vitro&nbsp;</i>osteogenesis and mineralization. <h3>Materials and methods</h3> <i>Smoc2</i> was stably overexpressed (Smoc2+) or silenced (Smoc2-). We also stably overexpressed <i>Smoc2</i> lacking the Calcium-binding domain (ΔCaBD). ATDC5 cells were cultured as micromasses. Gene expression of chondrogenic genes (<i>Acan</i>, <i>Col</i><i>2a1</i>, <i>Col10a1</i>), Wnt- and BMP genes was analysed by RT-qPCR. Safranin O, Sirius red, Alcian Blue and Alizarin red staining were performed to evaluate collagens, proteoglycans and mineralization. MC3T3 cells were cultured in monolayer. Alkaline phosphatase activity (ALP) was measured and mineralization was analysed by alizarin red staining. Gene expression of extracellular matrix genes, genes linked to mineralization and TGFβ superfamily genes was analysed by RT-qPCR. Intracellular signalling pathways (PKCα, ERK1/2, SMAD1/5/8, p38MAPK) were investigated by Western blot. Data were translationally validated in human periosteal and endothelial cells. <h3>Results</h3> Mineralization and ALP activity was reduced in Smoc2+ MC3T3 cells. Gene expression analysis showed an overall altered differentiation when overexpressing Smoc2. The activation status of PKCα, ERK1/2, p38MAPK and SMAD1/5/8 was significantly modified in Smoc2+ cells. We could not observe an effect on osteogenesis when silencing Smoc2. ΔCaBD cells however exhibited less of the inhibiting effects of Smoc2+ cells. Moreover we could observe partial restoration after addition of extracellular calcium to the culture medium of differentiating Smoc2+ cells. Alizarin red staining and ALP activity was reduced in hPDCs cultured in the presence of Smoc2+ supernatant compared to controls. However, hPDCs stimulated with ΔCaBD supernatants exhibited a lesser decrease of these markers compared to Smoc2+. Alizarin red quantification showed the same effect for HUVECs. In ATDC5 cells, Smoc2 overexpression altered chondrogenic markers and reduced Wnt and BMP signalling. Smoc2 silencing enhanced chondrogenic differentiation by increasing BMP signalling. <h3>Conclusions</h3> SMOC2 can regulate osteogenesis and chondrogenesis. Silencing of Smoc2 did not affect osteogenesis suggesting a limited endogenous role. SMOC2 appears to exert its effects through interaction with calcium and by interfering with BMP and Wnt signalling.
Case 15-2006
Authors: Raymond T. Chung, A. John Iafrate, Philip C. Amrein, Dushyant V. Sahani, Joseph Misdraji
Journal: New England Journal of Medicine (2006)

A 46-year-old woman had rapid onset of ascites, right upper abdominal discomfort, nausea, and vomiting. The serum–ascites albumin gradient was 1.2 g per deciliter. Venography demonstrated narrowing of the intrahepatic portion of the inferior vena cava; hepatic veins could not be visualized. Additional diagnostic procedures were performed.
PTU-050 The Value Of Gastroscopy In The Investigation Of Non Cardiac Chest Pain
Authors: SK Butt, K Besherdas
Journal: Gut (2014)

<h3>Introduction</h3> Non-cardiac chest pain (NCCP) is a common cause for referral to gastroenterology. Following the exclusion of a cardiac cause, NCCP is attributed to a variety of disorders, including gastroesophageal reflux disease (GORD), oesophageal dysmotility and oesophageal hypersensitivity, panic attack, musculoskeletal pain, and microvascular disease (cardiac syndrome X). GORD is the most prevalent cause of NCCP, accounting for up to 60% of cases. The prevalence of GORD in NCCP has been studied by pH monitoring and found to be 41% to 43%. <h3>Methods</h3> The aim of this study was to assess the diagnostic yield of gastroscopy as a first line investigation in the management of patients with NCCP. A retrospective analysis from September 2000–March 2013 of the endoscopic findings (using the Endoscribe and unisoft endoscopy reporting system) along with patient case notes, of consecutive patients with NCCP undergoing gastroscopy, in a district general hospital in North London was undertaken. <h3>Results</h3> A total of 146 patients (age range was 21 to 93 years with a male to female ratio of 68:78) were identified as having had an upper GI endoscopy for chest pain alone. 49/146 (34%) patients had a normal gastroscopy, 29/146 (20%) had evidence of GORD (oesophagitis, peptic stricture, Barrett’s oesophagus or hiatus, hernia), 27 patients (18%) had gastritis, and 11 (7%) with oesophageal motility disorders. Other findings included: 9 patients with duodenitis, 1 with gastric ulcer, 1 with oesophageal ulcer, 2 with gastric polyp. <h3>Conclusion</h3> In this study, the diagnostic yield of gastroscopy as to a oesophageal cause of NCCP is poor. 73% of patients with NCCP had a normal or incidencal benign non-contributory findings at endoscopy. Only 27% of patients had evidence of GORD or oesophageal dysmotility. The majority of these could have been diagnosed by high dose acid suppression therapy trial. We conclude that endoscopy in patients presenting to gastroenterology with NCCP is not a cost effective diagnostic tool and would suggest other modalities such as high dose proton pump inhibitor trial, barium swallow or oesophageal manometry/pH testing be explored as first line investigations. <h3>Disclosure of Interest</h3> None Declared.
Abstract 4617: Novel antiestrogens, SS1020 and SS5020, for breast cancer therapy and prevention
Authors: Shinya Shibutani, Naomi Suzuki, Xiaoping Liu, Hyo Jeong Kim, Y. R. Santosh Laxmi, Yoshinori Okamoto
Journal: Cancer Research (2010)

Abstract Tamoxifen (TAM) is widely used as a first-line endocrine therapy for breast cancer patients and as a prophylactic agent for women at high risk of developing this disease. Long-term administration of TAM has serious side effects, including endometrial cancer. These side-effects are due to the DNA damaging and/or estrogenic action of the drug. Raloxifene (RAL) approved as a chemopreventive agent for postmenopausal women at high risk for invasive breast cancer retains an estrogenic action. The poor bioavailability of RAL requires high doses to obtain an efficacy equivalent to that achieved with TAM. Several other antiestrogens developed were dropped out from the clinical trials due to their undesirable effects on the uterus. Therefore, development of new antiestrogen alternatives, but free of genotoxic and estrogenic potential, having significant antitumor potential beyond TAM and RAL is urgently required. SS1020 and SS5020 were developed as a new triphenylethylene antiestrogen and benzopyran antiestrogen, respectively, in our laboratory. Although TAM is a hepatic carcinogen and produces a high level of DNA damage in rats, both SS1020 and SS5020 did not produce such DNA damage. Unlike TAM and RAL, SS1020 and SS5020 had no detectable uterotrophic activity in OVX-rats treated even with a high dose (10 mg/kg). These indicate that SS1020 and SS5020 are free of genotoxic and estrogenic activities. The antitumor potential of SS1020 or SS5020 against 7,12-dimethyl-benz(a)anthracene-induced mammary carcinoma in rats and human MCF-7 breast cancer xenograft in athymic nude mice was superior to that of TAM and RAL. SS1020 has a much higher bioavailability than RAL, endowing it with higher antitumor potential than RAL. In addition, the development of estrogen-induced mammary tumor in rats was completed inhibited by dietary intake of SS1020, indicating that this compound has preventive potential. Taken together, SS1020 and SS5020 lacking genotoxic and estrogenic actions have anti-breast cancer activity superior to that of TAM and RAL. Both SS1020 and SS5020 are safer and more effective antiestrogen candidates for breast cancer therapy and prevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4617.