tbuckley/cabot-search huggingface dataset:
Abstract 4098: Triple negative breast cancer: Cisplatin plus TRAIL treatment enhance tumor and cancer stem cell death in vitro and in vivo models
Authors: Shuping Yin, Liping Xu, Kaladhar B. Reddy
Journal: Cancer Research (2011)

Abstract Women with triple negative breast cancer (TNBC) do not benefit from hormonal or herceptin-based therapies due to loss of target receptors such as ER, PR and HER-2 amplification. Current therapeutic approaches such as chemo- and/ or radiation therapy are in effective because cancer stem cells (CSC) were shown to be resistant to conventional chemo- and/or radiation therapy after treatment; they can regenerate all the cell types in the tumor through their stem cell-like behavior. The goal of this proposal is develop treatment strategy to effectively target tumor as well as CSC without significantly affecting the normal cells thereby improving therapeutic outcome or completely eliminate the tumor. Our data shows: (1) Treatment of TNBC cells, CRL-2335 and MDA-MB-468, with cisplatin plus Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) significantly enhanced cell death (by∼ 60-70%) as compared with untreated cells. (2) Similar treatment had a minimal effect (∼10-15% cell death) on CRL-8799 normal breast cells. (3) Human triple-negative breast cancers have high levels of cancer stem cells in breast carcinoma (∼ 41%) compared to surrounding benign/normal (∼5-10%) areas by CD44 positivity (cancer stem cell staining). (4) CRL-2335 TNBC cells treated with cisplatin plus TRAIL exhibited significant reduction (from ∼45% to ∼9% after treatment) in CSC. Treatment with cisplatin/TRAIL also inhibited the expression of EGFR, p63, survivin, Bcl-2 and Bcl-xL in TNBC cells. Specific inhibition of EGFR and/or p63 protein in TNBC cells by siRNA does not increase TRAIL-induced apoptosis. However, inhibition of survivin by siRNA enhances TRAIL-induced apoptosis. These observations suggested the possibility that Survivin played an important role in cisplatin plus TRAIL-induced apoptosis in TNBC cells. In vivo experiments, treatment of mice with cisplatin plus TRAIL resulted in a significant inhibition of CRL2335 xenograft tumors compared to untreated control tumors. Taken together the data suggests that cisplatin plus TRAIL treatment have the potential of providing a new strategy for improving the therapeutic outcome in TNBC patients. 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 4098. doi:10.1158/1538-7445.AM2011-4098
Abstract 1531: Macrophage FLT1 signaling activates an inflammatory response that promotes breast cancer distal metastasis.
Authors: Bin-Zhi Qian, Richard A. Lang, Jeffrey W. Pollard
Journal: Cancer Research (2013)

Abstract Macrophages are abundantly found in the tumor microenvironment enhance malignancy. At distal metastatic sites a distinct population of metastasis associated macrophages (MAMs) promotes tumor cell extravasation, seeding and persistent growth. Compared with lung resident macrophages, MAMs associated with breast cancer lung metastasis in pre-clinical models express high levels of cell surface FMS-like tyrosine kinase 1 (Flt1). Blockade of FLT1 signaling using specific inhibitory antibodies significantly inhibited the metastatic seeding and persistent growth of both human and murine breast tumor cell. This was confirmed using a genetic model of Flt1 tyrosine kinase domain (TK) ablation. Using bone marrow transplantation techniques, we further showed that this metastasis inhibitory effect was due to the lack of FLT1 signaling in hematopoietic cells. Furthermore, macrophage specific ablation of the tyrosine kinase domain of Flt1 by crossing Flt1 flox/flox mice with macrophage restricted Cre mice (Csf1r-Cre) also significantly inhibited tumor cell metastatic potential. Since Flt1 is not expressed by other hematopoietic cells and FLT1 inhibition did not affect the recruitment of MAMs, it indicated that specific FLT1 signaling in MAMs are important for their metastasis promoting functions. FLT1 regulated genes were identified by comparing gene expression profiles using microarray techniques of FACS sorted MAMs from mice treated with control and anti-FLT1 inhibitory antibody. Bioinformatics analysis showed that inflammatory response genes were highly enriched in these genes. Together, our studies indicated that FLT1 signaling is required for the activation of metastasis associated macrophages and regulates a set of inflammatory genes that promote breast tumor distal metastasis. Citation Format: Bin-Zhi Qian, Richard A. Lang, Jeffrey W. Pollard. Macrophage FLT1 signaling activates an inflammatory response that promotes breast cancer distal metastasis. [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 1531. doi:10.1158/1538-7445.AM2013-1531
Blood Pressure in Acute and Chronic Vasopressin Excess
Authors: Paul L. Padfield, Jehoida J. Brown, Anthony F. Lever, James J. Morton, James I. S. Robertson
Journal: New England Journal of Medicine (1981)

We studied 29 patients with malignant hypertension and 28 patients with the syndrome of inappropriate antidiuretic hormone secretion to assess the relation of plasma vasopressin to blood pressure in states of acute and chronic vasopressin excess. In the patients with malignant hypertension, vasopressin levels were elevated (13 +/- 2 pg per milliliter. [+/- S.E.M.]) but did not correlate with arterial pressure; however, in normal volunteers, blood pressure did not rise when vasopressin was increased beyond these levels through infusion of the peptide. In the patients with inappropriate antidiuretic hormone secretion, blood pressure was not elevated, but vasopressin was raised (39 +/- 7 pg per milliliter) and did not correlate with systolic or diastolic pressure. These data do not support the concept that an acute or chronic excess of vasopressin makes an important contribution to the regulation of blood pressure.
Diagnosis of Leukemia or Lymphoma in the Central Nervous System by Beta<sub>2</sub>-Microglobulin Determination
Authors: Giora M. Mavligit, Sarah E. Stuckey, Fernando F. Cabanillas, Michael J. Keating, Wallace W. Tourtellotte, S. Clifford Schold, Emil J Freireich
Journal: New England Journal of Medicine (1980)

To detect early relapse in the central nervous systems (CNS) of patients with acute leukemia or lymphoma, we measured levels of beta 2-microglobulin (beta 2 m) in serum and cerebrospinal fluid (CSF). CSF levels were significantly higher in patients with leukemia (P < 0.001) or lymphoma (P < 0.02) with clinical evidence of CNS involvement than in those without this complication. When serum and CSF levels were measured simultaneously, the CSF level of beta 2 m was significantly higher than the serum level in patients with acute leukemia and lymphoma with CNS involvement (P = 0.05), but not in patients without CNS involvement. Serial determination of CSF beta 2 m correlated well with the clinical appearance and disappearance of CNS involvement. These data suggest that serial and simultaneous determination of beta 2 m in serum and CSF may be useful in early diagnosis of CNS involvement and in monitoring intrathecal therapy in patients with acute leukemia or lymphoma.
A4.14 Selection and characterisation of rank specific thioaptamers
Authors: J Andras, L Simon, K Redlich, T Meszaros, P Mandl
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background/Objective</h3> The RANK (Receptor Activator of Nuclear Factor kappa B) receptor, located on the surface of osteoclasts plays a critical role in osteoclastogenesis. Aptamers are single-stranded oligonucleotides selected from a random single stranded RNA/DNA library to bind specifically to various targets (e.g. proteins) after folding into well-defined spatial structures. We set out to develop aptamers targeting the RANK receptor, a key marker of osteoclast differentiation. <h3>Materials and methods</h3> A single-stranded DNA library (approx. 10<sup>12</sup> different sequences) was amplified via polymerase chain reaction. Thiophosphate-modified deoxynucleotide triphosphates were used in order to generate nuclease-resistant thioaptamers. The glutathione S transferase-tagged, extracellular domain of the human RANK protein (AA 30–212) was produced by <i>in vitro</i> translation. After affinity purification, using this target, thioaptamers were selected by the iterative, <i>in vitro</i> SELEX (Systematic Evolution of Ligands by EXponential enrichment) process. The enriched single-stranded thioaptamer pool was amplified, cloned into bacteria, and 31 clones with inserts corresponding to the size of the aptamer were then sequenced. Thioaptamer candidates were screened by surface plasmon resonance (SPR). <h3>Results</h3> Thioaptamers were generated against the extracellular domain of the human RANK protein using the SELEX process. The interaction of nine randomly chosen thioaptamer candidates and their target protein was screened by SPR using the random initial oligonucleotide pool as negative control. A binding event was defined by a reflectivity variation (deltaR%) greater than 0,1. We identified four thioaptamers, which showed higher reflectivity variation (deltaR% 0.15–0.42), as opposed to the negative control (deltaR% 0.05), representing 1.4–3.9 fmol/mm<sup>2</sup> and 0.5 fmol/mm<sup>2</sup> surface coverage of the protein, respectively. <h3>Conclusion</h3> We identified four thioaptamers via the <i>in vitro</i> selection process, SELEX, which can recognise the extracellular domain of the human RANK protein. By further selection using transgenic cell lines and murine osteoclast cultures our aim is to select aptamers, which can specifically bind to both the murine and human RANK protein. Such nuclease-resistant aptamers may facilitate the identification of osteoclast precursors in human serum and may also be of potential therapeutic value as neutralising agents against RANK in murine models of inflammatory bone loss.
In-111 DTPA-Octreotide Scintigraphy for Disease Detection in Metastatic Thyroid Cancer
Authors: NICHOLAS J. SARLIS, LOUKAS GOURGIOTIS, LORI C. GUTHRIE, BARBARA GALEN, MONICA C. SKARULIS, THOMAS H. SHAWKER, NICHOLAS J. PATRONAS, JAMES C. REYNOLDS
Journal: Clinical Nuclear Medicine (2003)

Purpose The utility of In-111 DTPA octreotide scintigraphy (SRS) for disease detection in patients with metastatic thyroid carcinoma (TCA) remains controversial. The authors compared the sensitivity of In-111–based SRS, F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), and extensive conventional radiographic imaging (CRI) in this type of cancer. Methods SRS, FDG PET, and CRI were performed concurrently in 21 patients (age, 56.4 ± 12.9 years) who had aggressive TCA. Concordance rates % of lesion positivity among pairs of different techniques (A and B) were calculated as the ratio of the number of lesions positive with both techniques divided by the sum of the total number of lesions positive with technique A + total number of lesions positive with technique B, which was then multiplied by 200. Results The combined use of CRI, FDG PET, and SRS resulted in the detection of 105 lesions, presumed to be due to metastatic deposits. Sensitivities for SRS and FDG-PET imaging were 49.5% and 67.6%, respectively. The lesion detection concordance rates were as follows: CRI versus FDG PET, 80.8%; CRI versus SRS, 74.2%; and FDG-PET versus SRS, 58.6%. Importantly, SRS detected five unexpected lesions, which were negative by both CRI and FDG-PET imaging. In two representative patients, a positive correlation (Spearman’s rank = 0.71;P = 0.0576) existed between the percentage of lesional In-111 DTPA octreotide uptake and the standard uptake value in eight concordant lesions. Conclusion Although SRS has only moderate sensitivity for disease detection in metastatic TCA, sometimes it can reveal lesions that otherwise would be undetectable by either CRI or FDG-PET imaging.
Aspiration Pneumonitis and Aspiration Pneumonia
Authors: Paul E. Marik
Journal: New England Journal of Medicine (2001)

Aspiration is defined as the inhalation of oropharyngeal or gastric contents into the larynx and lower respiratory tract.1,2 Several pulmonary syndromes may occur after aspiration, depending on the amount and nature of the aspirated material, the frequency of aspiration, and the host's response to the aspirated material.2 Aspiration pneumonitis (Mendelson's syndrome) is a chemical injury caused by the inhalation of sterile gastric contents, whereas aspiration pneumonia is an infectious process caused by the inhalation of oropharyngeal secretions that are colonized by pathogenic bacteria. Although there is some overlap between these syndromes, they are distinct clinical entities (Table 1). Other . . .
Toxicity Profile and Outcomes of Antiefgr Treatment in Elderly Patients with KRAS Wild-Type Metastatic Colorectal Cancer. Experience of Virgen DE Las Nieves University Hospital
Authors: Conde-Herrero Verónica, González-Rivas Cynthia, González-Flores Encarnación, Ochoa Lucia, González-Astorga Beatriz, García-García Javier, Ruiz-Vozmediano Julia, Castillo-Portellano Lucia, Carmen Sanchez-Toro, Delgado Pérez Juan Ramón
Journal: Annals of Oncology (2014)
SAT0035 Variability in the Classification of Remission among Disease Activity Indices and Their Correlation: An Analysis From a Prospective, Observational Registry
Authors: W. G. Bensen, A. Jovaisas, C. Thorne, P. Baer, M. Khraishi, S. Dixit, D. Choquette, M. Starr, I. Fortin, D. Sholter, E. Rampakakis, J. S. Sampalis, A. J. Lehman, F. Nantel, M. Shawi, S. Otawa
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In recent years, disease remission in rheumatoid arthritis (RA) has been assessed using various disease activity indices such as the DAS28, SDAI, CDAI, ACR/EULAR-recommended Boolean definition and the Patient Activity Scale (PAS). <h3>Objectives</h3> The aim of this analysis is to describe the agreement between these five indices in classifying remission as well as to assess their correlation in a routine clinical care setting. <h3>Methods</h3> BioTRAC is an ongoing, prospective Canadian registry of rheumatology patients initiating treatment with infliximab or golimumab. In this analysis, data from RA patients who were treated with infliximab between January 2002 and June 2011 and had available information in all indices were used. The definitions for remission were as follows: DAS28-ESR &lt; 2.6; SDAI ≤ 3.3, CDAI ≤ 2.8; PAS ≤ 1.0. Factor analysis was used to assess the variability due to each of the indices while inter-item correlation was measured with the Pearson correlation coefficient. <h3>Results</h3> Seven hundred twenty five RA patients who had 2,897 complete assessments were included in the analysis. Non-remission was classified by all indices in 68.8% of the cases, while 31.2% achieved remission in one (12.4%), two (3.5%), three (3.4%), four (4.2%) and all five types (7.7%) of indices. Factor analysis showed that PAS accounted for 71.5% of the matrix variance, followed by DAS28-ESR (12.4%), SDAI (9.2%), CDAI (5.2%), and Boolean remission (1.6%), suggesting that PAS may reflect different aspects than the clinical indices. PAS remission revealed the lowest correlation with remission classified by the remaining indices (Table 1) and removal of any index, except PAS, would result in a lower overall Cronbach's alpha. <h3>Conclusions</h3> The results of this analysis show that variability exists in the classification of remission by various disease activity indices. This variability was found to be predominantly due to the Patient Activity Scale, a patient-driven composite tool, suggesting that the patient perception of disease activity may differ from that captured by clinical outcome measures. <h3>Disclosure of Interest</h3> W. Bensen: None Declared, A. Jovaisas: None Declared, C. Thorne: None Declared, P. Baer: None Declared, M. Khraishi: None Declared, S. Dixit: None Declared, D. Choquette: None Declared, M. Starr: None Declared, I. Fortin: None Declared, D. Sholter: None Declared, E. Rampakakis Employee of: JSS Medical Research, J. Sampalis Employee of: JSS Medical Research, A. Lehman Employee of: Janssen, F. Nantel Employee of: Janssen, M. Shawi: None Declared, S. Otawa Employee of: Janssen
P1-14-03: AVALUZ Study: First Line with Bevacizumab in Combination with Paclitaxel (P) and Gemcitabine (G) in Patients with HER-2 Negative Recurrent or Metastatic BC: PFS Analysis.
Authors: J Salvador, E Ciruelos, de Villena M Codes, A Jaen, M Gil, A Galan, A Murias, C Jara, la Haba J de, JM Baena, MJ Villanueva, J Bayo, I Blancas, E Gonzalez, D Perez, JR Mel, L Manso
Journal: Cancer Research (2011)

Abstract Background The combination of bevacizumab (B) with taxanes, capecitabine or anthracyclines has shown increased PFS in pts with mBC. The combination with G and P has been evaluated and has demonstrated high response rate and good toxicity profile. The aim of this study is to evaluate the efficacy and toxicity profile of the combination of B with G and P, providing an update of PFS and the toxicity experienced in all patients treated. Methods A phase II multicenter, national, open-label study in pts diagnosed of recurrent or metastatic HER-2 negative BC, treated with first line B 10 mg/kg, P 150 mg/m2 and G 2000 mg/m2 day 1 and 15 c/28 d until progression disease, unacceptable toxicity or medical decision. This abstract evaluates efficacy by PFS as primary endpoint and as secondary endpoints: response rate and toxicity profile (NCI CTC v3.0 criteria). Results From January 2009 to December 2009, 82 evaluable patients were recruited in 23 sites. The characteristic of the all of patients included (90) are: median age 51.5 (26-81), ER + 68%, PR + 59%, triple negative pts 19%, previous chemotherapy (neoadj or adj) 64.4% and ≥ 3 metastatic sites 21% of patients (19). The median cycles administered per pts was 7 (1-26) and the relative median dose intensity was 0.93 for B, 0.89 for P and 0.91 for G. Of the 75 patients with response assessment, the overall response rate obtained was 72% with a clinical benefit of 89.3% (80.6−95.28%) (CR 14.7% (11), PR 57.3% (43), SD 17.3% and PD 10.7%). Of the 82 patients with a median follow up of 16.5 m (0.16- 26.38), preliminary median PFS (43% events) for these pts was 11.48 m (8.98−15.72), the median duration of first response (MDR) was 12.4 m (7.47-NA) and the median OS was 21.35 m (20.72- NA). The one year OS% was 84.15% (74.27 - 90.47). Toxicity was generally manageable. Related AEs have been reported in 67/82 patients which were mostly mild or moderate. Safety analysis revealed 24 SAEs in 21 patients. Conclusions Bevacizumab in combination with paclitaxel and gemcitabine showed significant PFS compared with the published data with paclitaxel and gemcitabine and high clinical benefit with manageable safety profile. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-14-03.
UTILITY OF AN ADHERENCE TEST TO PREDICT THE PERCENT TIME IN THERAPEUTIC RANGE OF PATIENTS ANTICOAGULATED WITH DICUMARINIC ANTICOAGULANTS
Authors: Maria Cristina Lorenzo Carrion, Fernando Sokn, Gustavo Allende, German Jelusic, Gerardo Accastello, Jorge Tronge, Roxana Palacios, David L. Xavier
Journal: Journal of the American College of Cardiology (2016)
Understanding the Operative Experience of the Practicing Pediatric Surgeon
Authors: Fizan Abdullah, Jose H. Salazar, Colin D. Gause, Samir Gadepalli, Thomas W. Biester, Kenneth S. Azarow, Mary L. Brandt, Dai H. Chung, Dennis P. Lund, Frederick J. Rescorla, John H. T. Waldhausen, Thomas F. Tracy, Mary E. Fallat, Michael D. Klein, Frank R. Lewis, Ronald B. Hirschl
Journal: JAMA Surgery (2016)

The number of practicing pediatric surgeons has increased rapidly in the past 4 decades, without a significant increase in the incidence of rare diseases specific to the field. Maintenance of competency in the index procedures for these rare diseases is essential to the future of the profession. To describe the demographic characteristics and operative experiences of practicing pediatric surgeons using Pediatric Surgery Board recertification case log data. We performed a retrospective review of 5 years of pediatric surgery certification renewal applications submitted to the Pediatric Surgery Board between 2009 and 2013. A surgeon's location was defined by population as urban, large rural, small rural, or isolated. Case log data were examined to determine case volume by category and type of procedures. Surgeons were categorized according to recertification at 10, 20, or 30 years. Number of index cases during the preceding year. Of 308 recertifying pediatric surgeons, 249 (80.8%) were men, and 143 (46.4%) were 46 to 55 years of age. Most of the pediatric surgeons (304 of 308 [98.7%]) practiced in urban areas (ie, with a population >50 000 people). All recertifying applicants were clinically active. An appendectomy was the most commonly performed procedure (with a mean [SD] number of 49.3 [35.0] procedures per year), nonoperative trauma management came in second (with 20.0 [33.0] procedures per year), and inguinal hernia repair for children younger than 6 months of age came in third (with 14.7 [13.8] procedures per year). In 6 of 10 "rare" pediatric surgery cases, the mean number of procedures was less than 2. Of 308 surgeons, 193 (62.7%) had performed a neuroblastoma resection, 170 (55.2%) a kidney tumor resection, and 123 (39.9%) an operation to treat biliary atresia or choledochal cyst in the preceding year. Laparoscopy was more frequently performed in the 10-year recertification group for Nissen fundoplication, appendectomy, splenectomy, gastrostomy/jejunostomy, orchidopexy, and cholecystectomy (P < .05) but not lung resection (P = .70). It was more frequently used by surgeons recertifying in the 10-year group (used in 11 375 of 14 456 procedures [78.7%]) than by surgeons recertifying in the 20-year (used in 6214 of 8712 procedures [71.3%]) or 30-year group (used in 2022 of 3805 procedures [53.1%]). Practicing pediatric surgeons receive limited exposure to index cases after training. With regard to maintaining competency in an era in which health care outcomes have become increasingly important, these results are concerning.