tbuckley/cabot-search huggingface dataset:
Abstract 5123: A platform for examining the molecular basis for targeted therapy selection in colon cancer
Authors: Yi Chen, Elizabeth R. Wood, Yian A. Chen, Domenico Coppola, Erin Siegel, David Shibata, John M. Koomen
Journal: Cancer Research (2011)

Abstract Introduction: The quantitative evaluation of expression and post-translational modification of receptor tyrosine kinase targets in tumor tissues may enable the development of a molecular profile for the selection of targeted therapy in colon cancer. Experimental Procedures: Colon cancer cell lines are used to develop peptide-based quantitative assays for receptor tyrosine kinase protein expression and post-translational modification using SDS-PAGE protein fractionation prior to in-gel digestions and liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM). Additional downstream signaling proteins are also investigated. The sensitivity of each assay is tested using serial dilutions of cell lysate before translation to individual frozen tissue sections, which are bookmatched to hematoxylin and eosin stained slides for histology. A classification scheme for selection of targeted therapy is devised based on the amounts of protein expression and modification detected by LC-MRM. Data Summary: LC-MRM assays have been previously developed to monitor components of the beta catenin signaling pathway have been translated to measure protein expression in individual frozen tissue sections. Using the same methodology, LC-MRM assays have been developed for receptor tyrosine kinases (RTKs), including EGFR, Met, VEGFR, and IGF1R, as well as selected RTK interacting proteins and downstream signaling components. Implementing these novel assays in parallel with those already existing, an analysis of multiple signaling pathways in frozen section of colon tumors is conducted to enable a view of the tumor biology and assess the relevance of treatment with RTK inhibitors. Conclusions: The ability to examine cancer-related pathways in human tumors with quantitative mass spectrometry will produce improved understanding of the processes involved in tumor development and progression as well as elucidate the mechanisms of cancer cell response to chemotherapy. The coupling of quantitative proteomics with medical history and histology for comprehensive analysis of tumor tissues represents a promising step toward the ultimate goal of establishing a molecular basis for personalized medicine. This effort will demonstrate the feasibility of creating a quantitative proteomics method for tumor evaluation that could be used to translate basic science hypotheses into clinical samples and build a systems biology tool for patient assessment. 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 5123. doi:10.1158/1538-7445.AM2011-5123
Impact of the BCG vaccination policy on tuberculous meningitis in children under 6 years in metropolitan France between 2000 and 2011
Authors: T Van Bui, D Lévy-Bruhl, D Che, D Antoine, V Jarlier, J Robert
Journal: Eurosurveillance (2015)

In France, Bacillus Calmette–Guérin (BCG) vaccination by multipuncture device was withdrawn in 2006. In 2007, universal mandatory BCG vaccination was replaced by vaccination of high-risk children. To evaluate the impact of these changes on tuberculous meningitis (TBM) epidemiology, data on culture-positive and culture-negative (or unknown microbiological result) TBM in ≤5 years olds were collected from 2000–2011. Ten culture-positive and 17 culture-negative TBM cases were identified, with an annual incidence rate ranging from 0.16 to 0.66 cases per 10 million inhabitants. The average annual numbers of TBM cases were 2.7 and 1.8 from 2000–2005 and 2006–2011, respectively. In Ile-de-France where all children are considered at risk, the overall incidence rates were 1.14 and 0.29 per million for the two periods. In other regions where only at-risk children are vaccinated since 2007, rates were 0.30 and 0.47, respectively. None of these differences were significant. Annual incidence rates for each one year age group cohort were comparable before and after changes. Childhood TBM remains rare in France. No increase in incidence was observed after changes in BCG vaccination strategy. Ongoing surveillance should be maintained, as a slight increase in TBM in the coming years remains possible, in the context of suboptimal vaccination coverage of high-risk children.
Cerebral Sinovenous Thrombosis in Children
Authors: Gabrielle deVeber, Maureen Andrew, Coleen Adams, Bruce Bjornson, Frances Booth, David J. Buckley, Carol S. Camfield, Michèle David, Peter Humphreys, Pierre Langevin, E. Athen MacDonald, Brandon Meaney, Michael Shevell, D. Barry Sinclair, Jerome Yager, Jane Gillett
Journal: New England Journal of Medicine (2001)

Cerebral sinovenous thrombosis in children is a serious disorder, and information is needed about its prevention and treatment.
Abstract P4-15-05: Long-term outcome of breast cancer patients treated with radiofrequency ablation
Authors: M Earashi, M Noguchi, A Motoyoshi, H Komiya, H Fujii
Journal: Cancer Research (2012)

Abstract Background: Radiofrequency ablation (RFA) is considered to be the most promising non-surgical ablation technique for the treatment of small breast cancer. In feasibility studies, the ablated tumor was surgically removed after RFA, and the tumor cell viability were assessed by histological and/or immunohistological examinations. However, these assessments of tumor viability do not take the place of long-term follow-up in patients treated with RFA alone, because they do not allow for them to be followed up for recurrence after RFA, or to determine if there were any undesirable complications of this procedure. At present, few data are available regarding long-term follow-up of patients treated with this modality. Methods: Since 2005, we have performed RFA and sentinel lymph node (SLN) biopsy in 19 cases with invasive breast cancer less than 2.0 cm in greatest diameter. After SLN biopsy, a primary electrode (seven-array model 70 Starburst needle electrode; RITA Medical Systems, Mountain View, CA) was inserted into the tumor under real-time US guidance. Then, the prongs of the needle electrode were deployed over a distance of 3 cm in all cases, and the RF generator (RITA model 1500) was activated and set to automatic, with power at 20 W, temperature of 95°C, and an ablation time of 15 min. Axillary lymph node dissection (ALND) was performed in patients with positive SLNs. Several months after RFA therapy, the ablated tumor tissue was excised by multiple mammotome biopsy and examined histologically or immunohistochemically with H&amp;E staining, nicotinamide adenine dinucleotide (NADH)-diaphorase staining, and single-stranded (ss) DNA staining. All cases were followed-up after breast radiation and systemic therapies. Results: The mean tumor size based on the ultrasonographic maximum dimension was 1.3 cm (range: 0.5–2.0 cm). Although complete response was histologically confirmed in only 8 cases, NADH-diaphorase and ssDNA staining did not demonstrate any viable tumor cells in any of the ablated lesions. At a mean follow-up of 60 months (follow-up range, 37–82 months), there were no cases of in-breast recurrence, although one patient died due to hepatic metastases. Cosmesis of the conserved breast was excellent or good in all of the cases, but a hard lump was persistent after RFA in half of the cases. Conclusions: The long-term outcome of patients treated with RFA is encouraging with regard to cosmesis and local control. However, a persisted lump can cause patient discomfort, anxiety and fear. Therefore, further studies are needed to establish the optimal technique. Moreover, a prospective study will be required to determine the equivalency in local recurrence rates between the RFA therapy and conventional breast-conserving treatment. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-15-05.
FRI0069 Impact assessment of smoking in disease activity in a cohort of recent onset rheumatoid arthritis
Authors: L. Nuño, A. Villalba Yllan, D. Peiteado López, P. Alcocer Amores, S. García Carazo, A. Balsa Criado, E. Martín Mola
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> There is wide scientific evidence about the involvement of smoking in the susceptibility to rheumatoid arthritis. However, the effect of smoking on the activity of the disease and its clinical course is controversial. <h3>Objectives</h3> To analyze the impact of smoking on disease activity in a cohort of patients with recent onset rheumatoid arthritis. <h3>Methods</h3> We included a cohort of patients from an Early Arthritis Clinic (EAC), followed up between January 1993 and December 2012. All patients gave informed consent to the study. Patients were included with early arthritis (less than one year of disease duration to the onset), who met the criteria of the American College of Rheumatology (ACR) 1987 for RA at some time during the disease course, and were followed up for two years. Microcrystalline and infectious arthritis were excluded, as well as patients who previously had been treated with disease modifying antirheumatic drugs. Patients were monitored for clinical and analytical data using standardized protocols every six months. The influence of active smoking in disease activity, functional disability and serological variables were studied. Every six months we assessed: number of tender (out of 68) joints (NTJ), number of swollen (out of 68) joints (NSJ), DAS, change in DAS (ΔDAS), HAQ, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). <h3>Results</h3> 398 patients were included in the study, with a mean age at onset of 51.8 years (± 16.1 SD) and a predominance of women (77.6%). Patients were referred to the EAC with a mean of 17.7 weeks (± 13.1 SD) from the onset of symptoms. Active smokers were 27.6% of the patients. At baseline most patients had a subacute (88.7%), symmetrical (88.9%), RF-positive (81.3%), ACCP-positive (67, 5%) polyarthritis (83.1%). Smokers were younger at disease onset (49 ± 13.4 years smokers vs. 52.9 ± 13.4 in nonsmokers, p = 0.022), with a predominance of males (43% males vs. 23% women, p &lt;0.001), positive RF (30.5% vs. RF positive. 13.4% RF negative, P = 0.005) and positive ACPA (35.2% ACPA-positive vs. 16.2% ACPA-negative; p &lt;0.001). No significant differences in relation to smoking were found in terms of extension, course, symmetry, NTJ, NSJ, DAS, HAQ and ESR at months 0, 6, 12, 18 or 24. However, improvement in disease activity in active smokers was lower at 12 months (ΔDAS 1.29 ± 0.99 in smokers vs. 1.66 ± 1.30 in nonsmokers, p = 0.032) and at 24 months (ΔDAS 1.28 ± 1.20 in smokers vs. 1.9 ± 1.22 in non-smokers, p = 0.004). <h3>Conclusions</h3> Active smoking has a negative impact on the activity of patients with recent onset rheumatoid arthritis, with less improvement as compared to non-smokers. <h3>Disclosure of Interest</h3> None Declared
Skull Base Involvement by a Nasopharyngeal Carcinoma Shown by Tc-99m MDP SPECT But Not by Computed Tomography
Authors: S Saeed, S Haq, M Sohaib, A N Khan
Journal: Clinical Nuclear Medicine (2001)

Plain radiographs, computed tomography (CT), and more recently magnetic resonance imaging (MRI) are used routinely to stage carcinoma of the nasopharynx. Tc-99m methylene diphosphonate (MDP) SPECT is seldom used for local staging of the disease.Plain radiographs and CT were used to stage squamous carcinoma of the nasopharynx in a 50-year-old man with a left XII nerve palsy.Findings of the plain radiographs were normal, whereas the CT scan revealed a nonhomogenous hyperdense mass in the nasopharynx but intact underlying bone. Given the symptoms, a Tc-99m MDP planar scan was ordered and showed no enhanced uptake, but SPECT images obtained at the same time revealed markedly increased focal radiotracer uptake in the region of the tumor, indicating osseous involvement.Possible bony invasion with a nasopharyngeal carcinoma may be better shown with MDP SPECT than with planar isotope bone scans, plain radiographs, or CT.
DNA Content as a Prognostic Marker in Patients with Oral Leukoplakia
Authors: Jon Sudbø, Wanja Kildal, Björn Risberg, Hanna S. Koppang, Håvard E. Danielsen, Albrecht Reith
Journal: New England Journal of Medicine (2001)

Oral leukoplakia may develop into squamous-cell carcinoma, which has a poor prognosis. Risk factors for oral carcinoma have been identified, but there are no reliable predictors of the outcome in individual patients with oral leukoplakia.
Abstract 2328: Targeting angiogenesis: Anti-docking site peptides to Met receptor and nanotechnology
Authors: Anna Rita Cantelmo, Ilaria Sogno, Douglas M. Noonan, Chiara Focaccetti, Elisa Principi, Adriana Albini
Journal: Cancer Research (2012)

Abstract The Met tyrosine kinase receptor is involved in different cell responses during development and pathological conditions. In cancer, Met can promote growth, invasion, angiogenesis and tumor metastasis following the interaction with its ligand, the hepatocyte growth factor (HGF). We decided to develop angiogenesis inhibitors that target the HGF pathway, impairing tumour neo-vascularization and metastatic spreading. We investigated the anti-angiogenic proprieties of a synthetic peptide mimicking the intracellular Met-tail, which was delivered into cells by fusion with the internalization sequences from Antennapedia or HIV-Tat. We are also trying to do peptide delivery by using carbon nanotubes. In order to evaluate the effect of Met-derived inhibitors on angiogenesis, we treated HUVEC with peptides and we evaluated their ability to interfere with HGF-induced proliferation, migration and morphogenesis of endothelial cells in vitro and angiogenesis. Kaposi's sarcoma (KS), the most frequent neoplasia in patients with AIDS, which originates from endothelial origin and is highly vascularized, shows features compatible with the biological properties of HGF. We used KS as tumour model to test the effect of peptides on tumour growth in vivo. We found that the peptides inhibited ligand-dependent endothelial cell proliferation, migration and morphogenesis in vitro and interfered with HGF-dependent downstream signalling. In vivo, the peptides inhibited HGF-induced angiogenesis and Kaposi's sarcoma tumour growth. We also demonstrated that diacylglycerol kinases (DGK) contribute to the malignant phenotype of KS. The data obtained show that the peptides impair angiogenesis triggered by HGF, suggesting the use of anti-docking site compounds as therapeutic agents to interfere with the angiogenesis process. The development of angiogenesis inhibitors and the identification of new intracellular transducers effective in the high vascularised KS cells, open the possibility of a combination therapy that concomitantly interferes with tumour neo-vascularization and the malignant properties of KS. 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 2328. doi:1538-7445.AM2012-2328
The Duration of Oral Anticoagulant Therapy after a Second Episode of Venous Thromboembolism
Authors: Sam Schulman, Staffan Granqvist, Margareta Holmström, Anders Carlsson, Per Lindmarker, Peter Nicol, Sven-Gunnar Eklund, Sune Nordlander, Gerd Lärfars, Barbro Leijd, Olle Linder, Enno Loogna, Hans Walter, Stanka Viering, Martin Hjorth, Jonas Boberg
Journal: New England Journal of Medicine (1997)

A consensus has not been reached about the optimal duration of oral anticoagulant therapy after a second episode of venous thromboembolism.
Surveillance et traitement endoscopique des polypes de l'intestin grêle au cours du syndrome de Peutz-Jeghers: Résultats de 12 ans de suivi
Authors: S Scialom-Han, E Samaha, G Rahmi, J Edery, G Malamut, FM Canard, A Vienne, R Saade, PL Puig, C Cellier
Journal: Endoscopy (2015)

Le dépistage des polypes de l'intestin grêle dans le syndrome de Peutz-Jeghers (PJ) a évolué depuis l'introduction de nouvelles techniques d'exploration non invasives comme la vidéo- capsule endoscopique (VCE), l'entéro IRM (E-IRM) ou l'entéroscanner (E-TDM). La polypectomie lors d'une entéroscopie double ballon (EDB) ou spiralée (ES) est devenue le traitement de première intention de ces polypes. Nos objectifs étaient de: 1) décrire la rentabilité diagnostique de la VCE et de l'imagerie pour le dépistage des polypes du grêle et 2) d'évaluer le rendement thérapeutique de l'EDB ou l'ES dans le syndrome de PJ.
A bridge between cerebellar long-term depression and discrete motor learning: Studies on gene knockout mice
Authors: Masanobu Kano
Journal: Behavioral and Brain Sciences (1996)

Several commentators argue that there remains a gap between cerebellar long-term depression (LTD) studied in vitro and cerebellar functions such as motor learning. Recent developments in a gene-targeting technique for producing mutant mice defective in particular gene products has opened a new era for the study of synaptic plasticity and learning. There are three mutants in which cerebellar LTD are clearly deficient in vitro. Two of these mice show clear impairment in the conditioned eyeblink response, a paradigm known to involve the cerebellum. In contrast, one mutant with apparently normal cerebellar LTD showed no impairment in the conditioned eyeblink response. These new lines of evidence support the view that cerebellar LTD is a cellular basis for discrete motor learning.
GW25-e1155 New generation cryoballoon can improve long-term outcome of cryoablation for atrial fibrillation
Authors: Liu Jun, Yan Kaufmann, Ming Tang, Charalampos Kriatselis, Eckart Fleck, Gerds-Li Jinhong, Pihua Fang, Shu Zhang
Journal: Journal of the American College of Cardiology (2014)
Belimumab for Systemic Lupus Erythematosus
Authors: Bevra Hannahs Hahn
Journal: New England Journal of Medicine (2013)

A 20-year-old woman with SLE presents with disease flares and receives belimumab, a monoclonal antibody that binds to B-cell activating factor, inhibiting B-cell stimulation. Belimumab is considered for patients who do not have a response or have adverse effects with first-line therapies.
PREDICTORS OF DECREASED EXERCISE CAPACITY IN PATIENTS WITH HEART FAILURE AND REDUCED EJECTION FRACTION: ROLE OF RIGHT VENTRICULAR FREE WALL LONGITUDINAL STRAIN OBTAINED USING DIFFERENT ECHOCARDIOGRAPHY MACHINES AND ANALYTICAL SOFTWARES
Authors: Ahmed Ibrahim, Andres Schuster, Muhammad Hammadah, Wai Hong Tang
Journal: Journal of the American College of Cardiology (2016)
Dermatofibrosarcoma protuberans (DFSP): Mohs surgery technique and prognostic factors
Authors: M. Chacon, A. Gonzalez, G. Urrutia, G. Jankilevich, E. Domenechini, J. Kaplan, R. Chacon
Journal: Journal of Clinical Oncology (2004)

9066 Background: DFSP is a rare type of soft-tissue tumor accounting for 1,4% of all sarcomas with high propensity to recur locally. Wide local excision is the standard treatment with 15–60% local failure. Mohs surgery technique allows adequate margin control in all directions, appropriate to recurrences or tumors located in difficult areas to achieve free margins; it is not the standard procedure in DFSP that involves the underlying fascia or sites where preservation of normal tissue is not required. The objective is to report the outcome of patients (pts) surgically treated in one institution and to evaluate prognostic factors. Material and methods: we assessed retrospectively a cohort of pts with histological diagnosis of DFSP. Demographic data, tumor features and surgical procedure (Mohs excisions) were evaluated. Uni-multivariable statistical analysis were performed to determine prognostic factors in terms of local failure. Results: 30 pts have been evaluated (period 1998–2003). Pts characteristics: median age: 41 (17–62); male/female: 13/17; localization: trunk 15 (50%), head and neck 5 (17%), extremities 7 (23%), abdomen 3 pts; median size: 3,5 cm (1,5–12) and less than 3 mitoses/HPF was seen in 20 pts; 3 DFSP were classified as fibrosarcomatous. Surgery characteristics: wide local resections: 12 pts; Mohs technique: 9 pts (4 were recurrences) and 9 pts were admitted for reexcision (previous surgery in another institution), median clear margins were 2, 2.5 and 2 cm, respectively. 11/30 pts were operated by oncologist surgeons; median follow up:22 months (1–174); 5 pts (16,6%). developed local recurrences. There were not relapses in pts with Mohs procedure. The only statistical significant prognostic factor to local recurrence was fibrosarcomatous histology ( 2/3 relapsed). No distant or lymph nodes recurrence was seen. Conclusion: local recurrence of DFSP is the main problem. Multidisciplinary and expertise medical and surgical oncologists have to decide the type of surgical procedure and have to consider that a biological feature (fibrosarcomatous histology) is one of the most relevant prognostic factor to local recurrences after the hand of the surgeon. No significant financial relationships to disclose.
Abstract 5120: Functional genetic screens identify a rare isoform of RABL3 as a modulator of paclitaxel resistance in ovarian cancer
Authors: Qing Zhang, Takayo Ota, Tsuyoshi Ohta, Viji Shridhar, Jeremy R. Chien
Journal: Cancer Research (2012)

Abstract Recent RNA-sequencing studies have identified variant transcripts, fusion transcripts and novel transcripts in cancer. However, little is known about the role of these variant transcripts in tumor development. To identify a specific role of these variant transcripts in tumor development toward chemotherapy resistance, we generated a custom retroviral cDNA expression library from 10 ovarian tumors with resistance to chemotherapy. Retrovirues were generated from the custom library, and they were used to transduced exogenous genes into ovarian cancer cell line A1847, a cell line chosen for its sensitivity to paclitaxel. A1847 cells transduced with retroviruses carrying alkaline phosphatase was used as a control. Transuced cells were selected with 25 nM paclitaxel. 87 clones survived the selection in library-tranduced cells whereas none survived the selection in alkaline phosphatase-tranduced control cells. Forty seven clones survive the secondary screens. Sequence analysis of transduced genes in these surviving clones indicate that 4 paclitaxel-resistant clones contain RABL3 splice variant. Although 195 accessions corresponding to wildtype transcripts are reported in AceView, there is a single accession corresponding to RABL splice variant that we identified in this screen. RNAi-mediated downregulation of RABL3 resulted in enhance sensitivity toward paclitaxel in these resistant clones. Ectopic expression of RABL3 splice variant resulted in increased resistant to paclitaxel. Collectively, these results demonstrate the feasibility of performing functional genetic screens to identify novel splice variants involved in tumor development. 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 5120. doi:1538-7445.AM2012-5120