tbuckley/cabot-search huggingface dataset:
NT-06 * PHOSPHATIDYLSERINE-SELECTIVE TARGETING AND ANTICANCER EFFECTS OF SapC-DOPS NANOVESICLES ON BRAIN TUMORS
Authors: V. Blanco, Z. Chu, S. Vallabhapurapu, M. Sulaiman, A. Kendler, R. Curry, R. Warnick, R. Franco, X. Qi
Journal: Neuro-Oncology (2014)

Despite significant advances in our understanding of the biology of CNS tumors, the translation of such knowledge to novel and effective therapeutic strategies has been slow. Consequently, both primary (e.g., glioblastoma multiforme) and secondary (metastatic) brain tumors remain among the most intractable and fatal of all cancers. We have shown that nanovesicles consisting of saposin C (SapC) and dioleylphosphatidylserine (DOPS) effectively target and kill brain tumor cells both in vitro and in vivo. These actions are a consequence of the affinity of SapC-DOPS for phosphatidylserine (PS), an acidic phospholipid abundantly present in the outer membrane of a variety of tumor cells and tumor-associated vasculature. Here, we characterize SapC-DOPS bioavailability in a human glioblastoma orthotopic mouse model and reveal a time-dependent, tumor-specific extravascular accumulation of fluorescently labeled SapC-DOPS. Glioblastoma targeting by SapC-DOPS is abrogated after in vivo exposure to lactadherin, a protein that binds PS with high affinity. We also demonstrate that SapC-DOPS selectively targets brain metastases-forming cancer cells both in vitro, in co-cultures with human astrocytes, and in mouse models bearing brain metastases derived from human breast or lung cancer. We finally that SapC-DOPS cytotoxic activity against metastatic breast cancer cells in vitro, and prolongs the survival of mice with breast cancer brain metastases. Taken together, these results suggest that surface-exposed PS can be potentially useful as a novel lipid marker for diagnosis, monitoring, and therapy of central nervous system cancer, and highlights the potential of SapC-DOPS in the diagnosis and treatment of primary and metastatic brain tumors.
Abstract 3348: Immunophenotyping, xenotransplantability and molecular cytogenetic features of the sarcomatoid renal carcinoma cell line RCC52: Pathobiological significance
Authors: Chin-Hsuan Hsieh, Wen-Hui Weng, Kung-Lung Chuang, Ying-Tzu Chen, See Tong Pang, Hung-Chang Chen, Cheng-Keng Chuang, Shuen-Kuei Liao
Journal: Cancer Research (2010)

Abstract The immunobiology of sarcomatoid renal cell carcinoma (RCC) and how it has been transformed or progressed from clear cell-RCC are currently poorly understood. We analyzed a sarcomatoid renal carcinoma cell line (RCC52) derived from a primary clear cell renal carcinoma with intensive sarcomatoid differentiation, with respect to its immunophenotyping, molecular cytogenetic features and xenotransplantability. RCC52 cells grown as monolayers consisted of mostly small-sized epithelioid cells along with a small proportion of spindle/fibroblast-like cells, suggestive of growth of the sarcomatoid, but not clear cell component of the tumor. Cytofluorometric analysis revealed a phenotype of cell surface HLA-I−, E-CDH−, N-CDH−, EpCAM−, CD44+, CD54+, CD58+, URO1+ and URO10+ and cytoplasmic AE1+, E-CDH−, N-CDH+, Vimentin+, S100+ and VEGF+. Spectral karyotyping (SKY) show the chromosomal abnormalities in 22 metaphases examined to be 40-42&amp;lt;2n&amp;gt;,X,-Y[22]; der(2)t(2,3)(q35;q21)[20]; der(14)(14;17)(p11;q12)[22]; −3[11]; +7,+7[14]; −14[9]; −15[14]; −10[10]; −22[16]. Numerical imbalances were also assessed by comparative genomic hybridization, which are found to be consistent with the findings determined by banding and SKY. These results along with the documented genotype have established the identity of the RCC52 cell lines. Nude mouse xenografts resulting from RCC52 cell s.c. injection and the original tumor shared similar histopathology with mostly sarcomatoid elements with occasional clear cell areas, suggesting malignant potential of this cell line and the capability of sarcomatoid RCC cells to undergo transdifferentiation or dedifferentiation. The total HLA class I loss caused by the two distinctive mutations in the β2-microglobulin gene and loss of heterozygosity (LOH) in chromosome 15 observed recently (Cancer ImmunoI Immunother, 58:395-408, 2009) did not prevent sarcomatoid RCC52 cells from undergoing such transdifferentiation. Overall our results is of immunological (evasion of the host immunosurveillance) and pathobiological (progression/differentiation/transdifferentiation) significance, which forms the basis of further investigations with additional cell lines/ clones and tissues of clear cell-RCCs with sarcomatoid differentiation to confirm (i) loss HLA class I expression in most, if not all, sarcomatoid RCCs, and (ii) the proposed sequence of clear cell-RCC → fibroblast-like sarcomatoid RCC → epithelioid sarcomatoid RCC, which could in turn transdifferentiate into clear cell-RCC. 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 3348.
ET-08 * DEMETHYLATING THERAPY INDUCES DIFFERENTATION AND THERAPEUTIC RESPONSE IN IDH1 MUTANT MALIGNANT GLIOMAS
Authors: A. Borodovsky, G. Riggins
Journal: Neuro-Oncology (2014)

Isocitrate Dehydrogenase 1 (IDH1) mutations are frequent in progressive GBMs and the grade II and III gliomas from which they arise. The mutant IDH1 enzyme pathologically produces 2-hydroxyglutarate (2-HG) that metabolically inhibits α-ketogluterate dependent histone and DNA demethylases. This results in abnormal hypermethylation of genomic DNA that subsequently suppress cellular differentiation. We have investigated the use of the FDA approved drug, 5-azacytidine, and have shown it to be an effective agent in two preclinical models of IDH1 mutant glioma. To accurately model the IDH1 mutation oncogenic process, we developed a patient derived IDH1 mutant anaplastic astrocytoma model which produces 2-HG and shows a hypermethylated genome. Using this genetically and molecularly accurate model we have demonstrated the preclinical efficacy and mechanism of action of the FDA approved demethylating drug 5-azacytidine in vivo. Long term administration of 5-azacytidine resulted in reduction of DNA methylation of promoter loci, induction of glial differentiation, reduction of cell proliferation and significantly reduced tumor growth. Nearly complete tumor regression was observed by 14 weeks, resulting in a sustainable response and significant survival benefit. The sequence of events leading to a therapeutic response in IDH1 mutant gliomas appear to be first, inactivation of DNMT1, Loci specific genome demethylation, key alterations in the gene expression pattern, cellular differentiation followed by growth arrest. Overall, our goal is to find the most effective combination strategy for forcing differentiation in IDH1 mutant gliomas. It is based on targeting the epigenetic mechanism of transformation specific to the tumor, and xenograft models that have the native mutation. In is hoped that the results from this work will allow a better clinical trial design specific for IDH1 mutant glioma, as well as key biomarkers for therapeutic response.
A phase I study of BIBF 1120, an orally active triple angiokinase inhibitor (VEGFR, PDGFR, FGFR) in patients with advanced solid malignancies
Authors: C. P. Lee, G. Attard, L. Poupard, P. D. Nathan, J. S. de Bono, G. M. R. Temple, M. F. Stefanic, A. R. Padhani, I. R. Judson, G. J. Rustin
Journal: Journal of Clinical Oncology (2005)

3054 Background: BIBF 1120 is a potent orally available inhibitor of VEGF, PDGF and FGF receptor kinases. It also inhibits members of the Src family of tyrosine kinases (Src, Lck, Lyn). Methods: Pts with a variety of advanced solid malignancies were enrolled. BIBF 1120 as a continuous once daily dosing was started at 100mg/day and doubled in successive cohorts until the observation of ≥CTC grade (gr) 2 drug-related toxicities. Thereafter, escalation steps by no more than 50% were allowed. All pts underwent pharmacokinetic (PK) sampling. Dynamic contrast-enhanced MRI (DCE-MRI) studies were performed at baseline, days 2, 28 and 56 to assess functional tumour change following treatment. Results: To date, 39 pts (18M/21F) with a wide range of malignancies have been enrolled. Median age: 57 yrs (range: 22–77). ECOG PS 0/1: 17/22. 37 pts who had ≥21 days treatment were evaluable for toxicity. Median duration of treatment: 2 months (range: 8 days - 13 months). Pts were treated at 5 dose levels: 100mg/d (n=6), 200mg/d (n=6), 300mg/d (n=6), 400mg/d (n=14), 450mg/d (n=5). The most common toxicities were nausea, vomiting, diarrhoea, abdominal pain, fatigue (all ≤gr 2) and asymptomatic, reversible elevation in liver enzymes (gr 3 in 10 pts) seen at ≥200mg/d. MTD was identified as 400mg/d, with 2 pts experiencing dose-limiting liver enzyme elevation at 450mg/d which returned to baseline within 2 weeks of stopping treatment. 29 pts who had ≥8 weeks’ treatment were assessable for response: 10 pts had SD for 4, 5, 6, 7, 8.5, 11 months (ovarian, cervical, colon, prostate, renal cancer, GIST, NSCLC and leiomyomatosis). One pt with prostate cancer had significant prolongation of his PSA doubling time from 2 months to 10 months, and a pt with renal cancer had SD for 11 months. PK analysis showed in general increasing mean Cmax and AUC values with the dose, displaying moderate to high interpatient variability. Cmax values were reached ∼3 hrs after dosing. Mean t1/2ranged from 7.5–14.0 hrs. 28 pts underwent DCE-MRI studies (analysis on-going). Conclusions: BIBF 1120 was well-tolerated in pts with advanced malignancy and 400mg/d was defined as MTD. Study is on-going with further pts being treated at twice daily dosing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Boehringer Ingelheim Ltd. AstraZeneca, Boehringer Ingelheim, Celgene, Novartis, Topotargets Chroma, GlaxoSmithKline, Oncolytics Biotech, Roche Chiron, Human Genome Sciences, Pfizer
917 DEVELOPMENT OF PSYCHIATRIC SYMPTOMS DURING ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C: A RETROSPECTIVE STYUDY ON 590 SUBJECTS
Authors: G. Simonetti, G. Vitale, G. Taruschio, C. Cursaro, A. Scuteri, B. Lucia, C. Fabio, E. Loggi, L. Pirillo, A.F. Cicero, M. Bernardi, P. Andreone
Journal: Journal of Hepatology (2013)
Abstract 770: Lorvotuzumab mertansine (IMGN901) immune effector activity and its effect on human NK cells
Authors: Anna Skaletskaya, Yulius Y. Setiady, Peter U. Park, Robert J. Lutz
Journal: Cancer Research (2011)

Abstract Lorvotuzumab mertansine, or IMGN901, is a conjugate consisting of the cytotoxic maytansinoid, DM1, covalently linked to the monoclonal antibody, lorvotuzumab, which selectively targets CD56 (also called neural cell adhesion molecule or NCAM). This conjugate is currently being evaluated in clinical trials for the treatment of CD56+ solid tumors and multiple myeloma. It is able to inhibit tumor cell growth by disruption of microtubule dynamics through delivery of its cytotoxic DM1 payload; however, other potential cell killing mechanisms, such as the immune effector activity of its antibody component, have not been fully investigated. Herein, we report on the immune effector activity of the lorvotuzumab antibody and the lorvotuzumab mertansine conjugate and their effect on the function of CD56+ human primary NK cells in vitro. To investigate the effector activity of the antibody, lorvotuzumab was incubated with CD56+ tumor target cells in the presence of rabbit complement or purified human primary NK cells. The results show that this antibody fails to mediate complement dependent cytotoxicity (CDC) but induces antibody-dependent NK cell-mediated cytotoxity (ADCC) in dose-dependent manner. The complete conjugate showed ADCC activity comparable to lorvotuzumab alone, suggesting that DM1 conjugation did not alter the interaction between the Fc domain of the antibody and NK cell's Fc receptor. Since human primary NK cells express CD56, albeit at a low level, we tested whether lorvotuzumab mertansine or its antibody component could negatively impact the function of NK cells. The results demonstrate that incubation with this antibody or with this conjugate has no effect on rituximab-mediated ADCC activity of the NK cells. Furthermore, overnight exposure of human primary NK cells with lorvotuzumab mertansine did not change rituximab-mediated ADCC activity. In conclusion, the lorvotuzumab antibody has ADCC activity that is retained after DM1 conjugation. Furthermore, neither lorvotuzumab nor its DM1 conjugate, appear to affect the ability of NK cells (which are CD56+) to mediate ADCC through another antibody. 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 770. doi:10.1158/1538-7445.AM2011-770
Abstract 4278: Mapping deregulated pathways downstream of RTKs in cell line models.
Authors: Klarisa Rikova, Benjamin Hall, Anthony Possemato, Keri Mroszczyk, Kimberly A. Lee, Jian Min Ren, Ailan Guo, Daniel Mulhern, Yi Wang, Sean A. Beausoleil, Michael J. Comb
Journal: Cancer Research (2013)

Abstract In virtually all epithelial tumors, growth factor receptor activity is deregulated by activated mutations, genomic amplification, and autocrine loops. The dependence of tumor cell survival upon the driving oncogene has been called “oncogene addiction” and demonstrates the acute sensitivity of cancer cells to inhibition of the pathways driving their proliferation, growth and survival. Major questions regarding the sensitivity of solid tumors to targeted kinase inhibitors is why some tumors respond and others do not and why ones which respond still are able to develop resistance through the activation of other pathways. Robust, but not durable, response to receptor tyrosine kinase inhibitors (RTKIs) highlights the need to inhibit pathway activity at multiple levels. In this study, we identify extensive signaling networks downstream of receptor tyroine kinases (RTKs) across multiple spaces, including phosphorylation, acetylation, and methylation. We used the established method of TMT labeling coupled with serial peptide immunoprecipitation applied to profile drug-treated and untreated RTK pathway-addicted cancer cell lines. Quantitative analysis was performed to look at the effects of drugs on RTK-dependent cell lines: MKN45 (Met) with Crizotinib, H3122 (Alk) with Crizotinib, H1703 (PDGFRα) with Gleevec, and H3255 (EGFR) with Iressa. Phosphotyrosine, acetyl-lysine, methyl arginine, ATM/ATR substrate (s/tQ), and AGC/CAMK/STE family kinase motif were all selected for use in peptide immunoprecipitation which allowed us to characterize and quantify a broad PTM space. In this study we were able to identify and quantify hundreds of modification sites for phosphorylation, arginine methylation, and lysine acetylation. Those sites found to be drug-sensitive, including all PTM types, were used for pathway analysis of signaling downstream of each RTK disease driver. Citation Format: Klarisa Rikova, Benjamin Hall, Anthony Possemato, Keri Mroszczyk, Kimberly A. Lee, Jian Min Ren, Ailan Guo, Daniel Mulhern, Yi Wang, Sean A. Beausoleil, Michael J. Comb. Mapping deregulated pathways downstream of RTKs in cell line models. [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 4278. doi:10.1158/1538-7445.AM2013-4278
COMPUTED TOMOGRAPHY CORONARY ANGIOGRAPHY VERSUS STRESS CARDIAC MAGNETIC RESONANCE FOR THE MANAGEMENT OF SYMPTOMATIC REVASCULARIZED PATIENTS: A COST EFFECTIVENESS STUDY (STRATEGY STUDY)
Authors: Gianluca Pontone, Daniele Andreini, Marco Guglielmo, Cristina Rota, Saima Mushtaq, Andrea Baggiano, Virginia Beltrama, Anna Solbiati, Andrea Igoren Guaricci, Mauro Pepi
Journal: Journal of the American College of Cardiology (2016)
A novel traction system for esophageal endoscopic submucosal dissection
Authors: K. Ohata, K. Fu, M. Shouzushima, J. Hamanaka, A. Ono, T. Ito, Y. Tsuji, H. Chiba, N. Matsuhashi
Journal: Endoscopy (2012)

Recently, endoscopic submucosal dissection (ESD) has been used increasingly in Japan for the treatment of superficial esophageal carcinomas, as it provides a higher en bloc resection rate and lower incidence of recurrence than endoscopic mucosal resection (EMR), regardless of the size and shape of the targeted lesion [1]. However, compared with EMR, ESD is more time-consuming, more technically demanding, and associated with higher rates of complications such as bleeding and perforation [2]. In particular, submucosal dissection rather than the circumferential mucosal incision is challenging, as careful precoagulation of the vessels and adjusting of the depth of dissection are essential to avoid unnecessary bleeding and perforation [3]. We have therefore modified a novel traction system which can lift the submucosal layer to facilitate safer and faster submucosal dissection.
P98 Accuracy of routine antibiotic susceptibility testing of sputum samples in adult cystic fibrosis (CF) patients colonised with Pseudomonas aeruginosa (Psa)
Authors: A. Ashish, J. Fothergill, E. Mowat, S. Huq, M. Harris, C. Winstanley, M. Walshaw
Journal: Thorax (2010)

<h3>Background</h3> In CF patients with chronic Psa infection, the role of conventional antibiotic susceptibility testing (antibiotic disc diffusion on sputum subculture morphotypes according to BSAC protocols) is controversial, but many centres still rely on these methods when selecting treatment. However, morphotypes may exhibit up to six antibiograms, and this may contribute to the variable clinical response often noted. To look at this further, we performed additional Psa susceptibility testing on 26 sputum samples from 10 chronically infected CF patients provided over a 15-month period, and compared the results with those from the routine laboratory. <h3>Methods</h3> For each sputum sample, 40 colonies proportionately representative of morphological subtypes (mean 2, range 1–4) on the Psa selective plates were cultured onto Columbia plates. From these, single colonies were mixed with sterile distilled water to attain a standard optical density (10 MacFarland units), and 10 μl spread onto iso-sense plates and incubated overnight with tobramycin, meropenem, colomycin, ceftazidime, ciprofloxacin, and piperacillin/tazobactam antibiotic discs. Antibiotic sensitivity (break point 50% of isolates) was determined by the zone of inhibition as per standardised BSAC protocols. In total, 6240 analyses were performed. <h3>Results</h3> Although there was 100% concordance with the number of morphological subtypes of Psa with the routine laboratory, on multiple antibiotic susceptibility testing in 260 cases (25%) increased resistance was discovered. Overall, mean concordance between the routine diagnostic lab methodology and multiple antibiotic sensitivity testing was 70% (median 80%, IQR 60–100). However, in 15% of cases concordance was &lt;50%, suggesting that more detailed testing may have altered the choice of antibiotics used. <h3>Conclusion</h3> This study shows that routine microbiological methodology may under-represent antimicrobial resistance in Psa when patients are chronically infected. This may in part explain the clinical experience, and underlines the need for better microbiological techniques to aid the clinician in caring for these complex patients.
ACCURACY OF ECHOCARDIOGRAPHIC MEASURES OF THE EXERCISE-INDUCED CHANGE IN PULMONARY ARTERY PRESSURES: IMPORTANCE OF TRICUSPID REGURGITATION DOPPLER QUALITY
Authors: Annelieke C.M.J. van Riel, Alexander Opotowsky, Mario Santos, Jose Rivero, Andy Dhimitri, Michael Landzberg, Barbara Mulder, Berto Bouma, Aaron Waxman, David Systrom, Amil Shah
Journal: Journal of the American College of Cardiology (2016)
Updates: Cancer Drug Approved; New Leukemia Treatment
Authors: S. Jenks, K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Updates: Cancer Drug Approved; New Leukemia Treatment Get access Susan Jenks, Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 3, February 1995, Pages 167–170, https://doi.org/10.1093/jnci/87.3.167 Published: 01 February 1995
AB0301 Vascular Markers in Woman and in Men with Rheumatoid Arthritis
Authors: A. Lo Gullo, G. Mandraffino, M.A. Sardo, E. Imbalzano, F. Mamone, R. Lo Gullo, G. Bagnato, A. Saitta
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is associated with increased morbidity and mortality rates due to cardiovascular disease, and this occurs early in the disease process. In RA an impairment of the number and the activity of circulating progenitor cells, including CD34+ cells and endothelial progenitor cells, is involved in the development of endothelial damage and cardiovascular diseases (CVD). <h3>Objectives</h3> To evaluate CD34+ cell number and vascular markers in woman and men with RA. <h3>Methods</h3> We enrolled 48 patients (mean age 50.6±7.6), 22 men (mean age 51.1±7.9) and 26 women (mean age 50.2±7.4); patients were enrolled at the time of diagnosis, if they did not present with cardiovascular risk factors. CD34+, C-reactive protein (CRP), fibrinogen, carotid intima-media thickness (cIMT), Pulse wave velocity (PWV), were assessed at baseline. We investigated the relationships among cell number, inflammatory markers, and vascular parameters in woman and men. <h3>Results</h3> No differences in CD34+ cell number (1.79±1.34 vs 1.99±1.59), fibrinogen (361.9±64.2 vs 343.1±74.0), CRP (3.32±1.0 vs 3.12±0.96), PWV (7.77±2.3 vs 7.34±2.9), and cIMT (1.11±0.3 vs 1.14±0.1) between woman and men. In both groups was confirmed a correlation between CD34+ and Fibrinogen, CRP, PWV (all p&lt;0.01). <h3>Conclusions</h3> Despite RA affects more woman than men, we found no differences in vascular parameters between men and woman at the onset of the disease. <h3>References</h3> Kuller LH et al. Determinants of mortality among postmenopausal woman who report rheumatoid arthritis in the Woman9s Health Initiative. Arthritis and Rheumatism 2013. (Epub ahead of Print). Lo Gullo A et al. Circulating progenitor cells in rheumatoid arthritis: association with inflammation and oxidative stress. Scand J Rheumatol 2013 (Epub ahead of Print). <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5976
Gastrointestinal anthrax after an animal-hide drumming event - New Hampshire and Massachusetts, 2009.
Authors: L. Mayo, J. Dionne-Odom, E. A. Talbot, C. Adamski, C. Bean, E. R. Daly, F. Gao, R. Gougelet, J. Montero, D. Morse, J. Smith, R. Berry, F. McGarry, M. Wimsatt, L. Stamm, L. Madoff, C. Gauthier, M. Nalipinski, A. R. Hoffmaster, S. V. Shadomy, N. T. Pesik, T. L. Smith, L. J. Rose, K. Martinez, S. L. Burrer, K. Stauffer
Journal: MMWR Morbidity and Mortality Weekly Report (2010)
Case 16-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Robert G. Dluhy, Martha Bishop Pitman
Journal: New England Journal of Medicine (1991)

Presentation of CaseA 36-year-old man was admitted to the hospital because of a left adrenal mass.There was a history of von Hippel—Lindau disease. The patient enjoyed excellent health and was vigorous in his physical activities. Nine years before admission argon laser photocoagulation was performed on several retinal angiomas in the right eye, followed by penetrating diathermy, cryopexy, and a scleral-buckling procedure on the left eye in treatment of exudative retinal detachment. Seven months later the patient returned to the same hospital because of recurrent retinal detachment in the left eye, and another scleral-buckling procedure was performed. An intravenous . . .