tbuckley/cabot-search huggingface dataset:
Abstract 626: Specific targeting of cancer cells with RNA aptamers
Authors: Laura Cerchia, Carla Lucia Esposito, Silvia Catuogno, Margherita Iaboni, Giulio Draetta, Gerolama Condorelli, Vittorio de Franciscis
Journal: Cancer Research (2011)

Abstract A great promise in developing specific molecular probes for disease biomarker discovery and for diagnostic and therapeutic applications is recently represented by the intact cell-based SELEX (Systematic Evolution of Ligands by EXponential enrichment) strategy that allow to select nucleic acid aptamers against living cells. Indeed, using cell-SELEX to target proteins expressed on the cell surface permits to develop aptamers that are able to discriminate between even closely related target cells. This strategy has the advantage of a direct selection of ligands without prior knowledge of the target molecules and enables the identification of aptamers that bind large cell surface-specific markers, in their native conformation. Recently, by coupling a differential whole-cell SELEX protocol to human glioma and NSCLC cell lines we addressed the possibility to isolate aptamer molecules that may target cancer specific cell surface bound proteins. We isolated a set of 2’fluoro-pyrimidines modified RNA aptamers that are specific for different targets that are highly expressed on the tumor cell type used and underepresented on other cancer cell types tested. Remarkably, two of these aptamers bind at high affinity and high specificity to the extracellular domain of two human receptor tyrosine kinases (RTKs), EGFR and Axl respectively. Following binding, both aptamers hamper ligand-dependent receptor dimerization and autophosphorylation. Further, depending on the targeted RTK, the selected aptamers cause inhibition of cell proliferation and selective cell death in vitro and in vivo. Since an obvious advantage of RNA-based aptamers that bind cell surface receptors is the possibility to be conjugated to a siRNA and used as cargoes for tissue specific internalization, we thus developed a cell SELEX based protocol to enrich for aptamers that following binding to cell surface are rapidly internalized in a receptor-mediated manner. The whole-cell SELEX strategy holds a great promise in developing specific molecular probes for cancer biomarker discovery and for cancer diagnostic and therapeutic applications. 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 626. doi:10.1158/1538-7445.AM2011-626
Abstract 4585: Verification of prostate cancer biomarker candidates by nanoparticle-capture MRM
Authors: Claudia Fredolini, Alessandra Luchini, Francesco Meani, Paul Russo, Davide Tamburro, Temple Douglas, Caterina Longo, Guido Gambara, Weidong Zhou, Mark Ross, Francesco Novelli, Devis Collura, Giovanni Muto, Virginia Espina, David Ornstein, Lance A. Liotta, Emanuel F. Petricoin
Journal: Cancer Research (2010)

Abstract Prostate adenocarcinoma (PCa) is highly diffuse between older men, and biomarkers that allow discrimination of cancerous pathologies from benign diseases, identification of clinical aggressive cancer with high specificity and monitor cancer progression are required. Recently we applied a new workflow for the discovery of candidate biomarkers based on hydrogel nanoparticle capture of LMW serum borne analytes. Comparing serum from pre and post prostatectomy patients we identified 112 candidates biomarkers. Our novel nanoparticle technology provides a rapid and near 100% efficient means to capture and greatly amplify the resting concentration of LMW protein analytes. Since most of these markers do not have well performing specific antibodies commercially available, we utilized MRM to verify their differential expression as first identified by Orbitrap-MS/MS. Hydrogel nanoparticle serum pre-processing was used for both Orbitrap-LTQ based discovery and MRM verification such that the same analyte fractionation workflow was used but different downstream mass spectrometry. MRM was performed on a Thermo Quantum triple quadrupole-MS using the nanoparticle trapped analyte archive as the input for analysis. The following biomarker candidates were selected for MRM verification: Apolipoprotein E, Diacylglycerol kinase alpha, complement 1 subcomponent q B chain precursor, complement component 1 q subcomponent gamma polypeptide, serpin peptidase inhibitor, vitronectin precursor, angiotensinogen preproprotein, H4 histone family member J, fibronectin 1 isoform 2, orosomucoid 1 precursor, alpha-2-HS-glycoprotein, annexin I. Several prostate candidate biomarkers were verified by Nanoparticle capture-MRM, thus providing data supporting the use and continued improvement of this novel biomarker discovery system for the identification of protein biomarker panels for early disease detection and therapeutic monitoring. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4585.
CB-20 * SLC39A4 (ZIP4) INHIBITION SLOWS DOWN GBM CELL PROLIFERATION AND INTRACRANIAL TUMOR XENOGRAFT GROWTH
Authors: K. Zhang, J. Yang, L. Han, X. Cui, X. Sun, L. Chen, Z. Shi, J. Wang, C. Kang, M. Li
Journal: Neuro-Oncology (2014)

Our previous results demonstrated that ZIP4 was overexpressed in pancreatic cancer samples and down-regulation of ZIP4 inhibited pancreatic cancer growth and increased the survival of nude mice bearing orthotopic xenografts through IL6/STAT3 pathway. Only recently did we discover that high ZIP4 was significantly associated with higher glioma grade and worse prognosis of patients. However, the exact role of ZIP4 in glioma progression remains totally unknown. We transfected U87, LN229 and U251 GBM cells with ZIP4 knockdown and overexpression vectors to obtain stable GBM cell lines with different ZIP4 expression profiles. Western blot was used to confirm ZIP4 expression in these screened cell lines. Cell proliferation and invasion were examined by colony formation assay and transwell experiments. Then intracranial mouse GBM model were established to detect the orthotopic tumor growth and survival. Results showed that GBM-shV/shZIP4/V/ZIP4 cells were successfully obtained. ZIP4 inhibition decreased the proliferation and invasion of glioma cells. Moreover, ZIP4 inhibition slowed down tumor growth and prolonged the survival in vivo. Our results showed that aberrant expression of ZIP4 may contribute to GBM progression. ZIP4 might be a very promising target for GBM therapy.
Abstract 4779: K-983, an orally available small molecule inhibitor of FGFR, demonstrated prolonged survival in a mouse orthotopic gastric cancer model
Authors: Takayuki Furuta
Journal: Cancer Research (2012)

Abstract The receptor tyrosine kinase FGFR and its ligand fibroblast growth factor (FGF) play important roles in cell growth, migration, and survival. Dysregulation of the FGFR/FGF signaling pathway has been found in many human malignancies. K-983 was identified as a novel, potent, and orally active small molecule inhibitor of FGFR. The anti-tumor activity of K-983 was evaluated in a rat xenograft models. K-983 displayed dose dependent anti-tumor efficacy. K-983 demonstrated dose dependent inhibition of FGFR phosphorylation and prolonged survival in a mouse peritoneal dissemination model of gastric cancer. Furthermore, K-983 was examined using an orthotopic model of human scirrhous gastric cancer in nude mouse. K-983 (80 mg/kg) was orally administered once daily to the mice for 28 days. Histopathological examination revealed that K-983 inhibited tumor growth at inoculated site, invasion in gastric wall and metastasis to other organs. K-983 also significantly prolonged the survival of mice in this orthotopic tumor model. In summary, these results demonstrated the promising therapeutic potential of K-983 in anticancer therapy. 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 4779. doi:1538-7445.AM2012-4779
564 TREATMENT OF AUTOCHTHONOUS ACUTE HEPATITIS E IN IMMUNOCOMPETENT PATIENTS WITH SHORT TERM RIBAVIRIN: A MULTICENTRIC FRENCH EXPERIENCE
Authors: J. Nana, P. Borentain, R. Anty, F. Abravanel, C. Bureau, M.-A. Robic, L. Alric, P. Colson, J. Izopet, J.-P. Vinel, N. Kamar, R. Gérolami, J.-M. Peron
Journal: Journal of Hepatology (2012)
1387 IDENTIFICATION OF A NOVEL GENE ASSOCIATED WITH POLYCYSTIC LIVER AND KIDNEY DISEASES
Authors: W.R. Cnossen, R.H.M. te Morsche, A. Hoischen, C. Gilissen, M. Chrispijn, H. Venselaar, S. Mehdi, C. Bergmann, J.A. Veltman, J.P.H. Drenth
Journal: Journal of Hepatology (2013)
FRI0199 Does Lower Bone Mineral Density in A Single Hip PREDICT Fracture Better than Average Bone Mineral Density across Both Hips?
Authors: J. Parker, A. Oldroyd, M. Bukhari
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Low BMD taken from a single non-dominant hip is typically used to predict fracture; especially in FRAX. However, the average BMD from both hips could be used to predict fracture. No studies to date have questioned whether an average value from both hips predicts fracture better than using the lower single hip value. It is therefore important to consider whether combined hip BMD is superior at predicting fracture compared to the lowest BMD in a single hip. This may be important for clinical practice. <h3>Objectives</h3> To discover whether low BMD in a single hip predicts fracture better than the aggregate average BMD of both hips. <h3>Methods</h3> Dual X-ray Absorptiometry scan results of patients referred to a DGH between 2004 and 2010 were used. The following were recorded: age, sex, BMI and BMD. Patients were divided into a fracture and non-fracture group. Baseline characteristics were compared using students T-test for continuous and chi<sup>2</sup> test for categorical variables. Logistic models were fitted to determine the predictors of fracture, one using the non-dominant hip, one using the dominant hip and one using the mean BMD of both hips. Fit of the model was assessed by fitting receiver operating characteristic (ROC) curves <h3>Results</h3> 14,584 patients were included in the study and 27% had sustained a fracture. Baseline demographics are summarised in Table 1. Linear regression analysis comparing left and right mean hip BMD showed coefficient of 0.948 with 95% confidence interval 0.943-0.953 (p&lt;0.05). Logistic regression analysis is summarized in Table 2. <h3>Conclusions</h3> There is little difference between using the lowest, highest or combined hip BMD to predict fractures. When the total left hip BMD is lowest, this predicts fracture just as well as the higher right or total combined (OR 11.86 vs 11.77 vs 11.49 respectively). A similar pattern is found using the right total hip BMD as lowest (OR 10.72 vs 12.81 vs 12.63 respectively). Linear regression analysis shows that there is a tendency for patients to have similar BMD in both hips; therefore low BMD on one side means it is likely there will be low BMD in the contralateral hip. This may partially explain some of the findings. This is the first time this has been demonstrated, further studies are required to validate this adjusting for potential confounders. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4948
Abstract 2620: Contribution of risk variant in miR-125b binding site of BMPR1B in women of African ancestry with breast cancer
Authors: Toshio F. Yoshimatsu, Yonglan Zheng, Jing Zhang, Dezheng Huo, Olufunmilayo I. Olopade
Journal: Cancer Research (2012)

Abstract MicroRNAs play a fundamental role in gene regulation by selective binding to the 3′ UTR of specific mRNAs. Dysregulation of this post-transcriptional regulatory mechanism, in turn, has emerged to be an important process in cancer etiology. Recently a particular single nucleotide polymorphism (SNP) at mir-125b binding locus of BMPR1B, rs1434536, was reported as significant risk factor for breast cancer pathogenesis in Caucasians. The BMPR1B gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The C/T allelic variation within the target site disrupts the regulation of miR-125b, whereby increased BMPR1B expression ultimately elevates disease risk. To validate whether rs1434536 also contributes to breast cancer risk in women of African ancestry, we performed a case-control study of 805 breast cancer cases (422 African Americans (AA) and 383 Nigerians (NG)) and 786 controls (402 AA and 384 NG). The average age (±SD) was 46.9 ± 11.9 years for cases and 45.1 ± 12.4 years for controls. Genotyping was conducted using polymerace chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Test for Hardy-Weinberg equilibrium (HWE) suggested that there was no deviation from HWE (P &amp;gt; 0.05) in AA, or NG. Pearson's chi-squared tests showed that this SNP was significantly associated with breast cancer in AA (p=0.03) but not in NG (p=0.96). After adjusting for age in the logistic regression, we found the heterozygous genotype CT was associated with nearly 30% lower odds of breast cancer compared to CC genotype (OR=0.74, 95% CI 0.55-0.99; p=0.04) in AA. In the pooled analysis adjusting for both age and sites, the CT genotype was not statistically significant (OR=0.85, 95% CI 0.68-1.06; p=0.15). The common allele T (allele frequency = 0.60) was the risk allele in the previous study conducted in Caucasians, whereas the T allele was the minor allele in subjects of African descent (allele frequency = 0.129 in NG and = 0.232 in AA). In conclusion, our preliminary study found the T allele to have a trend for a protective effect in AA, which is disagreement with the observation made in the original study. Thus, this study indicates the need for replication studies in diverse populations to validate whether rs1434536 is a risk variant for specific subtypes of breast cancer. 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 2620. doi:1538-7445.AM2012-2620
D-DIMER/CARDIAC TROPONIN-I RATIO IS A SIMPLE AND USEFUL PARAMETER IN DIFFERENTIATING ACUTE PULMONARY EMBOLISM WITH TROPONIN ELEVATION FROM ACUTE NON-ST ELEVATION MYOCARDIAL INFARCTION
Authors: Kye Hun Kim, Jae Yeong Cho, Hyun Ju Yoon, Youngkeun Ahn, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park
Journal: Journal of the American College of Cardiology (2015)
FRI0031 Better Outcomes of Disease Activity in A Large Cohort of Rheumatoid Arthritis Patients Treated under Treat to Target Recommendations:
Authors: A. Palomino, V. Giraldo, P. Santos-Moreno, G. Saavedra-Martinez, L. Villarreal, D. Gomez, J. Bello-Gualtero, L. Tamer
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The importance of early effective therapy, implications of disease activity in progression and use of composite disease activity measures in rheumatoid arthritis (RA), led to developing of defined therapeutic targets and tools to achieve them resulting in the Treat to Target (T2T) initiative. This strategy is being used last 2 years in Colombia in a specialized in RA center. <h3>Objectives</h3> The aim of this study was to describe global change in Disease Activity Score 28 (DAS28) using T2T strategy for a 24 month period in a large cohort of patients from a Colombian specialized in RA center. <h3>Methods</h3> A descriptive cross-sectional study was performed. Records of patients from specialized in RA center were reviewed; those patients were followed-up under T2T standards. Clinical follow-up was designed by the authors according to DAS28 as follows: every 3-5 weeks (DAS28 &gt;5.1), every 7-9 weeks (DAS28 ≥3.1 and ≤5.1), and every 11-13 weeks (DAS28 &lt;3.1). In case of DAS28 &gt;3.2 it was mandatory to introduce adjustments in treatment based on a predetermined clinical guideline. We calculated percentages and averages from this data and distributed patients in four groups: remission (Rem), low disease activity (LDA), moderate disease activity (MDA) and severe disease activity (SDA). Global change in DAS28 was determined at beginning, 6, 12, and 24 months an assessed using Chi-square test. The median of each variable was analyzed using t-Student assuming normality for DAS28 distribution and the level of disease activity was analyzed using Pearson9s statistics. <h3>Results</h3> 1046 patients were included in this study, 865 (82.7%) women and 181 (17.3%) men. Mean age 60.1 years. With regard to treatment it was found that 340 (32.5%) patients were treated with biologics, and 706 (67.5%) patients with conventional therapy. The mean of DAS28 was 3.4 at the beginning and 24 months after was 2.6. The difference of medians for each variable showed improvement with statistical significance (p&lt;0.00). <h3>Conclusions</h3> This study shows improvement of DAS28 in a cohort of RA patients from a specialized center in Colombia treated under recommendations of T2T strategy; it was found a global increase in the percentage of patients in remission (REM) and decrease in moderate and severe disease activity (MDA/SDA) group. This study shows de importance of T2T strategy for following-up and treating this disease. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4830
Improved Survival in Patients with Locally Advanced Prostate Cancer Treated with Radiotherapy and Goserelin
Authors: Michel Bolla, Dionisio Gonzalez, Padraig Warde, Jean Bernard Dubois, René-Olivier Mirimanoff, Guy Storme, Jacques Bernier, Abraham Kuten, Cora Sternberg, Thierry Gil, Laurence Collette, Marianne Pierart
Journal: New England Journal of Medicine (1997)

We conducted a randomized, prospective trial comparing external irradiation with external irradiation plus goserelin (an agonist analogue of gonadotropin-releasing hormone that reduces testosterone secretion) in patients with locally advanced prostate cancer.From 1987 to 1995, 415 patients with locally advanced prostate cancer were randomly assigned to receive radiotherapy alone or radiotherapy plus immediate treatment with goserelin. The patients had a median age of 71 years (range, 51 to 80). Patients in both groups received 50 Gy of radiation to the pelvis over a period of five weeks and an additional 20 Gy over an additional two weeks as a prostatic boost. Patients in the combined-treatment group received 3.6 mg of goserelin (Zoladex) subcutaneously every four weeks starting on the first day of irradiation and continuing for three years; those patients also received cyproterone acetate (150 mg orally per day) during the first month of treatment to inhibit the transient rise in testosterone associated with the administration of goserelin.Data were available for analysis on 401 patients. The median follow-up was 45 months. Kaplan-Meier estimates of overall survival at five years were 79 percent (95 percent confidence interval, 72 to 86 percent) in the combined-treatment group and 62 percent (95 percent confidence interval, 52 to 72 percent) in the radiotherapy group (P=0.001). The proportion of surviving patients who were free of disease at five years was 85 percent (95 percent confidence interval, 78 to 92 percent) in the combined-treatment group and 48 percent (95 percent confidence interval, 38 to 58 percent) in the radiotherapy group (P<0.001).Adjuvant treatment with goserelin, when started simultaneously with external irradiation, improves local control and survival in patients with locally advanced prostate cancer.
Efficacy of Pamidronate in Reducing Skeletal Complications in Patients with Breast Cancer and Lytic Bone Metastases
Authors: Gabriel N. Hortobagyi, Richard L. Theriault, Lester Porter, Douglas Blayney, Allan Lipton, Clive Sinoff, Helen Wheeler, Joseph F. Simeone, John Seaman, Robert D. Knight, Maika Heffernan, Dirk J. Reitsma, Ian Kennedy, Simon G. Allan, Kathleen Mellars
Journal: New England Journal of Medicine (1996)

Bisphosphonates such as pamidronate disodium inhibit osteoclast-induced bone resorption associated with cancer that has metastasized to bone.
The Value of Antibiotics in Diabetic Surgery
Authors: M. J. Kuffel, L. N. Irvin, D. H. Hooker, D. P. Foster
Journal: New England Journal of Medicine (1948)

IF A diabetic patient must submit to major surgery, what is his prognosis? Or if a person has inherited the recessive genes of diabetes, where should his interest be directed to prevent a frank diabetic state and the inevitable associated surgery? According to Root,1 practically every diabetic patient, at some time in his life, is operated on, and the prognosis is materially affected by the efficiency of diabetic control during the years preceding the emergency.The reduction of the mortality in diabetic surgery over the years has been striking. Before the discovery of insulin in 1922, the surgical mortality stood . . .
AB0032 Association of ADAMTS12 polymorphisms with rheumatoid arthritis in korean population:
Authors: S.-S. Nah, J.-H. Shim, S.J. Lee, H.-J. Kim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A disintegrin and metalloproteinase (ADAM) with thrombospondin type 1 motif, 12 (ADAMTS12) is a degradative enzyme that interacts with the degradable fragments of cartilage oligomeric matrix protein, which is a prominent noncollagenous matrix component in articular cartilage. ADAMTS12 has been observed in the cartilage, synovial fluid and serum of arthritis patients, and may play an important role in the pathogenesis of arthritis. <h3>Objectives</h3> In this study, we investigated whether the genetic polymorphisms of <i>ADAMTS12</i> are associated with rheumatoid arthritis (RA) in a Korean population. <h3>Methods</h3> To observe the association between <i>ADAMTS12</i> and RA, we genotyped three single nucleotide polymorphisms (SNPs) (rs1364044, intron C/T; rs10461703, intron C/T; rs25754, missense Thr1495Ile) of <i>ADAMTS12</i> using a direct sequencing method in 303 RA patients and 495 control subjects. Multiple logistic regression models were performed to analyze the genetic data. SNPStats and SNPAnalyzer Pro programs were used to estimate odds ratios, 95% confidence intervals, and p values. Bonferroni’s correction (p<sup>c</sup>) was conducted to obtain a defined result. <h3>Results</h3> Of the three SNPs, the genotype frequency of rs10461703 was associated with the development of RA (p<sup>c</sup>=0.0024 in the co-dominant model; p<sup>c</sup>=0.0009 in the dominant model; p<sup>c</sup>=0.0006 in the log-additive model). The allele frequency of rs10461703 also showed a significant difference between RA and controls (p<sup>c</sup>&lt;0.0001). The C allele frequency of rs10461703 was lower in the RA group (36.6%) than in the control group (45.7%), whereas the T allele frequency of rs10461703 in the RA group (63.4%) was higher than that in the control group (54.3%). The other two SNPs (rs1364044 and rs25754) were not associated with the development of RA. However, we did not find any association between the three tested SNPs and RA patients according to clinical features including erythrocyte sedimentation rate, C-reactive protein level, rheumatoid factor (+ and -) and bone erosion (+ and -). <h3>Conclusions</h3> Our results suggest that <i>ADAMTS12</i> may be a susceptibility gene for RA development in the Korean population. <h3>Disclosure of Interest</h3> None Declared
CLINICAL OUTCOMES IN PATIENTS WITH CORONARY VASOSPASTIC ANGINA PRESENTING WITH ACUTE MYOCARDIAL INFARCTION
Authors: Sung Woo Cho, Taek Kyu Park, Jeong Hoon Yang, Young Bin Song, Joo-Yong Hahn, Jin-Ho Choi, Sang Hoon Lee, Hyeon-Cheol Gwon, Minsun Kim, Juwon Kim, Seung-Hyuk Choi
Journal: Journal of the American College of Cardiology (2016)