tbuckley/cabot-search huggingface dataset:
Abstract 5723: Inhibition of angiogenesis in the mouse heart by ionizing radiation
Authors: Chryso Kanthou, Zahra Gharaei, Julia Haagen, Sarah Jane Lunt, Constantino Reyes-Aldasoro C. Reyes-Aldasoro, Wolfgang Doerr, Gillian M. Tozer
Journal: Cancer Research (2012)

Abstract The heart is a critical dose-limiting organ during radiotherapy. In patients treated for breast cancer or Hodgkin's disease, regions of the heart can receive radiation doses in excess of 40 Gy. More recently, epidemiological and clinical studies suggested that even moderate to low radiation doses increase the risk of cardiovascular disease that can present years after the initial exposure. Radiation can cause cardiac microvascular damage but the mechanisms of pathogenesis of radiation-induced heart disease have not been clearly defined. Cardiac injury triggers repair processes in the myocardium requiring neovascularisation. Here, we investigated latent effects of ionizing radiation on angiogenic responses in the mouse heart. We also assessed the effects of radiation on cardiac endothelial responses and angiogenesis in vitro. The hearts of C57BL/6 and ApoE-/- mice were locally irradiated with 0.2 to 16 Gy and animals were sacrificed at 20, 40 and 60 weeks post-irradiation. Formation of angiogenic sprouts was assessed in ventricular heart explants embedded in fibrin gels. The angiogenic capacity of irradiated hearts was also assessed through a novel fibroblast-endothelial “self-assembling assay” we developed. Mouse hearts were enzymatically digested into a single cell suspension and cultured for 10 days. Within 5 to 7 days, endothelial cells began to form capillary-like structures surrounded by fibroblasts and pericytes, modeling the angiogenic process. Cardiac endothelial cells were also irradiated in vitro and effects on migration and capillary-tube formation on a fibroblast bed were established. Radiation caused a dose-dependent inhibition of endothelial sprout formation in explants from both mouse models. Significant changes were observed at 8 and 16 Gy after 20 weeks and at ≥2 Gy after 40 or 60 weeks post irradiation. Irradiation also significantly reduced the adherence and growth of extracted cardiac cells and inhibited the quantity and quality of the capillary-like structures formed in the “self-assembling” model. In vitro, irradiation (≥0.2 Gy) inhibited the migration of cardiac endothelial cells in scratch wound assays and capillary-like formation on a fibroblast bed. Our data show that radiation causes persistent and progressive vascular damage and suppresses angiogenic activity in the heart. Angiogenesis was inhibited at doses likely to be delivered during thoracic radiation in cancer patients. Impairment of the angiogenic response could lead to further ischemia and degeneration in the myocardium and contribute to the development of heart disease. 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 5723. doi:1538-7445.AM2012-5723
P11.02 * PRIMARY CEREBRAL LYMPHOMA: TREATMENT WITH HIGH DOSE METHOTREXATE IN A MONO-INSTITUTIONAL EXPERIENCE
Authors: P. Gaviani, G. Simonetti, E. Lamperti, A. Petruzzi, A. Innocenti, A. Botturi, L. Fariselli, A. Silvani
Journal: Neuro-Oncology (2014)

Primary central nervous system lymphoma (PCNLS), is a rare brain tumor that represents about 3% of all CNS tumors, with a median age at diagnosis of 63 years. In immunocompetent patient, the addition of high-dose methotrexate (MTX >1 g/m2) to radiotherapy (RT) has substantially improved the median OS, with a median survival of 3-4 years and a rate of long-term survival of 20 - 30 %, representing the current standard treatment for PCNSL. Older patients are an important subgroup that accounts for approximately half the cases of PCNSL and age is the most influential prognostic factor that invariably affects treatment decision. Combined treatment exposes patients to delayed neurotoxicity that may occur as early as 6 to 12 months after treatment. Patients older than 60 years are particularly susceptible to delayed neurotoxicity (progressive leukoencephalopathy in 50% to 80% of cases). To assess the efficacy and the toxicity of MTX chemotherapy we retrospectively analyzed consecutive patients with an histological proven newly PCNSL treated in our Institution from January 2005 to May 2013. Patients were treated with parenteral MTX with dosage stratified for age (2000 mg/mq in patients >70 years and 3500 mg/mq in patients <70 years). Primary endpoint was TTP with particular attention to age ≥or <70 years; secondary endpoint was acute/subacute toxicity due to the treatment. A total of 52 patients were included in this study: 30 males and 22 females, with Median age 60,84 years (range 20 and 81 years) and median KPS 70 (range 40-100); patients aged 70 years and over were 17 (9 males and 8 females). The median number of cycles administered were 3.5 (range 1-9); the median interval from one cycle to another was 17 days (range 8-36 days). Median TTP after chemotherapy in the whole group of patients was 3,33 months (5 months after chemo and radiotherapy) while in patients ≥ 70 years was 4.73, and in patients < 70 years was 2.97. Patients with KPS ≥ 70 reached a median TTP of 10.4 months while patients with KPS < 70 had a median TTP of 2.57 months (no difference in KPS in patients > or < of 70 yeras old). We found a mild toxicity in the whole group of patients without statistically significant difference in patients > or < 70 years. In particular patients ≥ 70 years had moderate creatinine and BUN elevation in 3/17 patients with a delay of cycle administration but without dose reduction, myelosuppression in 6/17, in two cases with chemotherapy discontinuation. PCNSL in the elderly remains sensitive to MTX. Although outcome is worse in older patients with PCNSL, that should not preclude the use of aggressive therapy because the majority of patients respond and improve clinically. The current study has several limitations, including the inherent biases of a retrospective study. Other important variables, including QoL measures, and detailed neurocognitive assessment were not available in all patients.
Abstract 3196: Androgen receptor 3’ untranslated region (UTR): a conundrum and a significant therapeutic opportunity.
Authors: Girish C. Shukla, Kavleen Sikand, Jey S. Ebron
Journal: Cancer Research (2013)

Abstract Master transcriptional regulator Androgen Receptor (AR) remained a fascinating and an enigmatic molecule, particularly in Prostate cancer biology. Major impetus in PCa research is currently focused on the development of new generation of therapeutics to target AR expression, especially in castration-resistant stage of the disease. 920 amino acid coding AR gene encompasses over 180 kilobase (kb) of X-chromosome containing eight exons that produces a nearly 10.7 kb AR mRNA. The fully processed mature AR mRNA account for only 26% of total coding capacity and most of the transcript codes for noncoding regions that includes 5’ and 3’ UTRs. However, functional roles of UTRs in AR gene expression, principally its regulatory involvement in development of CRPC remained indefinable. Our research is focusing on understanding the functional roles of 6.8 kb long AR 3’ UTR in AR gene expression and especially the molecular mechanism that revitalizes AR expression in CRPC. We have shown that a number of regulatory noncoding miRNAs play a critical 3’ UTR targeting role in AR gene expression and has potential therapeutic implications. Here we show a synergistic approach of targeting AR expression mediated via its 3’ UTR, using a miRNA cocktail combinatorial approach. In addition, we are investigating the potential functional association of 3’ UTR in AR gene expression and implication in PCa. Citation Format: Girish C. Shukla, Kavleen Sikand, Jey S. Ebron. Androgen receptor 3’ untranslated region (UTR): a conundrum and a significant therapeutic opportunity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3196. doi:10.1158/1538-7445.AM2013-3196 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
PTU-117 Imaging Hepatic Neutrophil Migration with Indium-111-(111In)-Radiolabelled Leucocytes: A Novel Non-Invasive Diagnostic Test for Severe Alcoholic Hepatitis
Authors: J R Potts, M Howard, S Verma, A M Peters
Journal: Gut (2013)

<h3>Introduction</h3> Clinical diagnosis of severe alcoholic hepatitis (SAH) can be unreliable and liver biopsy often problematic. Neutrophil infiltration is a key histological feature of SAH and predicts corticosteroid (CS) response (1). We assessed the use of radiolabelled leucocyte scintigraphy to diagnose SAH through <i>in vivo</i> imaging of hepatic neutrophil migration. Liver signals at <sup>111</sup>In-leucocyte scintigraphy portray margination at 30min post injection (PI) and destruction at 24h PI, and are normally matched. We hypothesised that both these functions would be impaired in SAH and liver activity would increase between 30min and 24h due to neutrophil migration. <h3>Methods</h3> 16 patients with SAH (Discriminant Function 54.8 ± 16.3, 14 biopsied), 14 with inactive alcoholic cirrhosis (Child-Pugh score 5.4 ± 0.9) and 11 controls were recruited. Abdominal gamma camera images were obtained 30min and 24h after IV injection of autologous 111In-labelled leucocytes and change in liver activity expressed as a 24 h:30 min ratio. Biopsies in SAH were stained with the granulocyte marker CD15 and parenchymal neutrophils quantified across 10 high power fields. <h3>Results</h3> Liver activity significantly increased in SAH but was static or fell in cirrhotic and normal control groups (24h:30min liver ratio 2.18 (IQR 1.62) versus 0.97 (0.28) and 0.78 (0.15) respectively, p &lt; 0.001). Figure 1 shows example gamma camera images. Liver activity ratios in SAH correlated with histological neutrophil infiltration (ρ = 0.571, p = 0.041) and microautoradiography demonstrated intact intrahepatic radiolabelled leucocytes as the likely source of 24h liver activity. Prominent 30min lung activity was a consistent finding in SAH, providing <i>in vivo</i> evidence of neutrophil priming. There was no correlation between imaging/histology and CS response, likely due to the small heterogeneous study group. <h3>Conclusion</h3> 111In-labelled leucocyte scintigraphy is a novel technique for assessment of hepatic neutrophil migration in SAH. It has potential to be a non-invasive diagnostic tool and may help to prospectively identify those likely to respond to CS. <h3>Disclosure of Interest</h3> None Declared <h3>Reference</h3> Mathurin P, Duchatelle V, Ramond MJ, <i>et al.</i> Survival and prognostic factors in patients with severe alcoholic hepatitis treated with prednisolone. <i>Gastroenterology</i> 1996; <b>110</b>:1847–53.
CVD BIO biochemotherapy of metastatic melanoma - one center clinical experience
Authors: P. Langiewicz, J. Paprocka-Langiewicz, T. Sarosiek, J. Zolnierek, P. Rzepecki, W. Pawlak, C. Szczylik
Journal: Journal of Clinical Oncology (2004)

7563 Background: Patients with histologically confirmed skin metastatic melanoma were treated with CVD BIO biochemotherapy regimen with subcutaneously administrated IL-2. We analyzed safety, response rate and survival. Methods: Between Dec 1996 and Mar 2003 39 patient were treated with CVD (DTIC 800 mg/m2d.1, CDDP 20 mg/m2 d.1–4 and vinblastine 1,6 mg/m2 d. 4 and 5) IV combined with SC interleukin-2 (9 mlnU/m2 d.1–4) and interferon alpha (5mlnU/m2 d.1–5)(BIO). We planned sequential treatment schedule: 3 cycles CVD (d.1–5, 22–26, 43–47) and 3 cycles BIO ( d. 6–10, 17–21, 27–31). Results: Median age was 44 years (22–62). Ten patients (26%) before biochemotherapy had metastasectomy (NED before treatment), twenty (51%) had metastases only in lymph nodes, soft tissue and lungs. Toxicities were recorded according WHO criteria for all patients receiving at least one cycle of CVD chemotherapy and one immunotherapy (BIO) -39 pts (100%). Patients received total 119 cycles of CVD and 121 cycles of BIO. 35 patients (90%) received full CVD-BIO treatment, as was planned. 25 pts (64%) with measurable disease were evaluable for response. We observed 6 CR (24%) and 8 PR (32%). 34 pts (87%) were evaluable for time to progression (TTP), progression free survival (PFS) and overall survival (OS) . Non-hematological grade 3 or 4 toxicity was moderate: fever 7 pts (17,7%), nausea and vomiting 3 pts (7,7%), anorexia 3 pts (7,7%), flu-like syndrome 3 pts (7,7%). Grade 3 or 4 neutropenia was confirmed in 9 pts (23,1%), thrombocytopenia in 5 pts (12,8%) and anemia in 3 pts (7,7%). There were no treatment-related deaths. Median TTP (months) was 6,5 (2–49), PFS 7 (2–49) and OS 11,5 (5–64+). In small group (10 pts) after surgical cytoreduction of distant visceral metastases we note median OS 21 month ( 9–64+) p=0,03, and OS 14 month ( 5–57) p=0,11 for patients with metastases only in lymph nodes, soft tissue and lungs. Conclusions: CVD BIO with subcutaneously administrated of IL-2 is effective, well tolerated and accepted for patients. Treatment was beneficial predominantly for patients with good performance status before treatment, with minimal residual disease or with lymph nodes, soft tissue or lungs metastases. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Servier
TCTAP C-055 Successful Treatment with Angle Modification Using a Reversed Guidewire Technique for the Acute-Angle Bifurcation Lesion
Authors: Takahiro Mori, Yoshinobu Murasato, Emiko Ejima, Masaaki Nishihara, Katsuhiko Takenaka
Journal: Journal of the American College of Cardiology (2015)
FRI0110 Epcs is A Determinant of Vascular Function and Atherosclerosis in As
Authors: A. Syngle, N. Garg, I. Verma, P. Krishan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Ankylosing Spondylitis (AS) is an inflammatory disease associated with premature atherosclerosis.<sup>1</sup> We hypothesized that depleted endothelial progenitor cells (EPCs), mediators of inflammation and Carotid intima media thickness (cIMT) are associated with atherosclerosis in other populations <sup>2</sup> and would be increased and associated with the severity of atherosclerosis in patients with AS. <h3>Objectives</h3> The aim of this study was to assess EPC population, and its potential relationships with inflammatory cytokines, vascular function and marker of atherosclerosis in AS. <h3>Methods</h3> We compared 30 patients of AS with 22 healthy controls. CD34 +, CD133+, were used to quantify EPCs using flow-cytometry. Flow-mediated dilatation (FMD) was assessed by using Angiodefender™ (Everest Genomic Ann Arbor, MI, United States). Carotid intima media thickness (cIMT) was measured using ultrasonography. Pro-inflammatory cytokines, TNFalpha, IL-1, IL-6, and inflammatory disease activity measures Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Functional ability was monitored by using Bath Ankylosing Spondylitis Functional Index (BASFI) were also assessed. <h3>Results</h3> EPCs were significantly decreased in AS patients as compared to healthy controls (p=0.01). We also found significantly increased CIMT in AS group compared with controls (p=0.01). FMD was significantly impaired and inflammatory disease activity measures i.e. BASDAI, BASFI and serum concentrations of IL-6, TNF-α and IL-6 were higher in AS patients than controls (all P&lt;0.05). Total cholesterol and high density lipoprotein cholesterol levels are significantly impaired in AS patients than controls (P&lt;0.05). Significant positive correlation was observed between the percentage of EPCs, FMD and HDL cholesterol (P&lt;0.05) and negative correlation was found between EPC and CIMT, IL-6, and BASDAI. <h3>Conclusions</h3> EPCs are significantly associated endothelial dysfunction and subclinical atherosclerosis in AS. EPC depletion in AS possibly results from severe disease and elevated IL-6. Higher CV risk in AS is possibly also contributed by reduced EPCs, altered lipid profile and higher level of pro-inflammatory cytokines. Impaired EPC may lead to accelerated vascular remodelling due to chronic impairment of endothelial function. <h3>References</h3> Ross R. N Engl J Med. 1999;340:115–126. Tanasescu C et al. Rom J Intern Med. 2009;47:103-108. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5228
FDG Uptake in Gestational Sac
Authors: HALUK ALIBAZOGLU, RICHARD KIM, AMJAD ALI, ALEXANDER GREEN, GREGORY LA MONICA
Journal: Clinical Nuclear Medicine (1997)

A 39-year-old woman, with a newly diagnosed malignant melanoma of the right calf had negative CT scans of chest, abdomen, and thighs. Two weeks later, a whole body F-18 FDG PET scan showed a focal area of markedly increased metabolic activity in the left side of the pelvis, above and slightly posterior to the urinary bladder. A week later, ultrasound showed a well formed 5-week-old gestational sac in the left side of the uterus. The patient had a 10-year history of birth control pill use and reported she had menstrual bleeding a week before a CT scan.
Abstract 1749: Role of eIF3a in DNA repair and lung cancer chemo sensitivity
Authors: Jiye Yin, Zizheng Dong, Zhaoqian Liu, Jianting Zhang
Journal: Cancer Research (2011)

Abstract Drug resistance is one of the major obstacles in successful chemotherapy of lung cancers. However, the mechanism of resistance is not yet clearly understood. Recently, eIF3a that plays an important role in translational control and regulation of gene expression was found to correlate negatively with prognosis in human cervical and esophageal cancers. We, thus, hypothesize that eIF3a may be an important factor in lung cancer response to chemotherapy by regulating the expression DNA repair proteins. Examination of 211 lung cancer tissue samples revealed that eIF3a expression negatively correlates with responses of the patients to cisplatin treatment. Ectopic over-expression or knockdown of eIF3a reduced or increased cellular resistance, respectively, to cisplatin, doxorubicine, and etoposide (VP-16) in cell lines as determined using MTT assay. Altering eIF3a expression also changed DNA repair activity as well as the expression of DNA repair proteins. We conclude that eIF3a possibly suppresses the synthesis of DNA repair proteins via translational control, which in turn contributes to the increased sensitivity to DNA-damaging anticancer drugs. 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 1749. doi:10.1158/1538-7445.AM2011-1749
CONTRAST AND COLOR CLINCH THE DIAGNOSIS: LESSONS FROM AN OUT OF PROPORTION, SUBACUTE POST-MYOCARDIAL INFARCTION COMPLICATION
Authors: Vlad Zaha, Judith Meadows, Marcos Amuchastegui, Catherine Dillon, Ian Crandall, Pramod Bonde, Brian Cambi, Carlos Mena-Hurtado, Henry Cabin, Lissa Sugeng
Journal: Journal of the American College of Cardiology (2015)
Addition of Lomustine (CCNU) to Induction and Post-Remission Chemotherapy for Fit Elderly AML Patients without Unfavorable Cytogenetics: Results of the Lamsa-2007 Goelams Trial
Authors: Arnaud Pigneux, Christian Recher, Marie C Bene, Julien Asselineau, Ariane C. Mineur, Thibaut Leguay, Jacques Delaunay, Caroline Bonmati, Romain Guieze, Isabelle Luquet, Pascale Cornillet-Lefebvre, Catherine Lacombe, jean-Christophe Ianotto, Mario Ojeda, Mathilde Hunault, Anne Banos, Bruno Lioure, Marc Bernard, Eric Jourdan, Norbert Vey, Hacene Zerazhi, Hichri Yosr, Roselyne Delepine, Rachid Salmi, Francois Dreyfus, Jean-Yves Cahn, Norbert Ifrah
Journal: Blood (2015)
Associations between Long-Term Air Pollutant Exposures and Blood Pressure in Elderly Residents of Taipei City: A Cross-Sectional Study
Authors: Szu-Ying Chen, Chang-Fu Wu, Jui-Huan Lee, Barbara Hoffmann, Annette Peters, Bert Brunekreef, Da-Chen Chu, Chang-Chuan Chan
Journal: Environmental Health Perspectives (2015)

BackgroundLimited information is available regarding long-term effects of air pollution on blood pressure (BP) and hypertension.ObjectiveWe studied whether 1-year exposures to particulate matter (PM) and nitrogen oxides (NOx) were correlated with BP and hypertension in the elderly.MethodsWe analyzed cross-sectional data from 27,752 Taipei City residents &gt; 65 years of age who participated in a health examination program in 2009. Land-use regression models were used to estimate participants’ 1-year exposures to particulate matter with aerodynamic diameter ≤ 10 μm (PM10), coarse particles (PM2.5–10), fine particles (≤ 2.5 μm; PM2.5), PM2.5 absorbance, NOx, and nitrogen dioxide (NO2). Generalized linear regressions and logistic regressions were used to examine the association between air pollution and BP and hypertension, respectively.ResultsDiastolic BP was associated with 1-year exposures to air pollution, with estimates of 0.73 [95% confidence interval (CI): 0.44, 1.03], 0.46 (95% CI: 0.30, 0.63), 0.62 (95% CI: 0.24, 0.99), 0.34 (95% CI: 0.19, 0.50), and 0.65 (95% CI: 0.44, 0.85) mmHg for PM10 (10 μg/m3), PM2.5–10 (5 μg/m3), PM2.5 absorbance (10–5/m), NOx (20 μg/m3), and NO2 (10 μg/m3), respectively. PM2.5 was not associated with diastolic BP, and none of the air pollutants was associated with systolic BP. Associations of diastolic BP with PM10 and PM2.5 absorbance were stronger among participants with hypertension, diabetes, or a body mass index ≥ 25 kg/m2 than among participants without these conditions. One-year air pollution exposures were not associated with hypertension.ConclusionsOne-year exposures to PM10, PM2.5–10, PM2.5 absorbance, and NOx were associated with higher diastolic BP in elderly residents of Taipei.CitationChen SY, Wu CF, Lee JH, Hoffmann B, Peters A, Brunekreef B, Chu DC, Chan CC. 2015. Associations between long-term air pollutant exposures and blood pressure in elderly residents of Taipei City: a cross-sectional study. Environ Health Perspect 123:779–784; http://dx.doi.org/10.1289/ehp.1408771
Phase I/II trial of X-396, a novel anaplastic lymphoma kinase (ALK) inhibitor, in patients with ALK+ non-small cell lung cancer (NSCLC)
Authors: Karen L. Reckamp, Jeffrey R. Infante, George R. Blumenschein, Heather Wakelee, Corey A. Carter, Jon P. Gockerman, Christine Lovly, Gary Dukart, Kimberly Harrow, Chris Liang, James J. Gibbons, Leora Horn
Journal: Journal of Thoracic Oncology (2016)