tbuckley/cabot-search huggingface dataset:
Comparison of F-18 FDG to I-123 and I-131 Scans in Thyroid Carcinoma
Authors: S M Bakheet, J E Powe, M M Hammami, M Ahmed
Journal: Clinical Nuclear Medicine (1997)

A patient who was in remission with papillary thyroid cancer was investigated for recently increasing thyroglobulin levels. I-123 diagnostic whole-body imaging showed a focus of faint uptake centrally in the thyroid bed, whereas an F-18 FDG PET whole-body scan showed two foci in the right side of the neck, most likely in the cervical lymph nodes, and was essentially negative in the thyroid bed. An I-131 postablation scan confirmed all three neck foci, and showed an incidental pericardial effusion. F-18 FDG PET imaging might be helpful in thyroid cancer patients with elevated thyroglobulin levels and equivocal radioiodine scans and may help differentiate residual tumor from a thyroid remnant.
Abstract 4411: γH2AX as a marker of genomic instability predicts cisplatin sensitivity in triple negative breast cancer cells
Authors: Brian D. Lehmann, Josh A. Bauer, Melinda E. Sanders, Bapsi A. Chakravarthy, Jennifer A. Pietenpol
Journal: Cancer Research (2011)

Abstract Triple negative breast cancers (TNBCs), that are hormone receptor negative (estrogen and progesterone) and lack HER2 amplification have limited treatment options. There is increasing evidence that TNBC is a heterogeneous disease and that patients with TNBC differentially respond to standard chemotherapies, which in many cases predicts for outcome. A portion of TNBC is considered genomically unstable as evidenced by array CGH analysis and the high frequency of BRCA1/2-mutations in TNBC patients. The identification of tumors displaying significant genomic instability may allow pre-selection of patients for select therapies (e.g. cisplatin, PARP inhibitors) that are more effective in the setting of deficient DNA damage response signaling. To determine if inherent genomic instability exists in TNBC, cell lines were analyzed for the phosphorylated histone variant 2AX (γ-H2AX) by immunohistochemistry and immunofluorescence as a marker of endogenous DNA damage. Tissue microarray blocks were created from 28 TNBC cell lines as well as appropriate controls to develop experimental conditions for γ-H2AX detection. TNBC cell lines significantly varied in the levels of baseline γ-H2AX foci, with BRCA1/2-mutant cell lines (HCC1937, HCC1599 and SUM149PT) having some of the highest levels. The presence of γ-H2AX foci in the absence of stress correlated with sensitivity (IC50) to cisplatin (R2 = 0.620), but not PARP inhibitors (R2 = 0.006). In addition to cell lines, we demonstrate that γ-H2AX staining can be detected in archived formalin-fixed, paraffin-embedded breast cancer tissue with approximately 25% of the tumors displaying high levels of nuclear γ-H2AX staining. Therefore endogenous levels of γ- H2AX may have potential use as a clinical biomarker to identify patients that will benefit from treatment with DNA-damaging agents. 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 4411. doi:10.1158/1538-7445.AM2011-4411
Phase II Study of Sorafenib with Anastrozole To Overcome Resistance to Aromatase Inhibitors (AIs) in Patients with Hormone Receptor Positive (ER/PR+) AI Resistant Metastatic Breast Cancer (MBC).
Authors: C. Isaacs, M. Wilkinson, M. Liu, Y. Ottaviano, G. Chung, R. Warren, E. Jennifer, P. Cohen, K. Smith, A. Novielli, J. Castle, R. Slack
Journal: Cancer Research (2009)

Abstract Background: Studies are focusing on agents which may overcome endocrine therapy resistance in patients with hormone receptor positive (ER/PR+) MBC. Activation of the Ras-Raf-MAPK pathway has been proposed as a mechanism of resistance to AIs. Thus, we are evaluating the use of sorafenib (SOR), a multi (Raf)-kinase inhibitor targeting both tumor cells and the tumor vasculature in patients with AI-resistant MBC.Methods: We are conducting a phase I/II study of SOR in combination with anastrozole 1 mg po daily (ANT) in MBC patients utilizing an optimal 2-stage design. Eligible patients include post-menopausal women with ER/PR+ MBC with disease recurrence or progression on an AI. Participants may not have received &amp;gt; 2 prior chemotherapies for MBC. Primary objectives are to determine the recommended dose and clinical benefit rate (CBR) (CR, PR and SD ≥ 24 weeks) of SOR with ANT. Secondary objectives are to determine toxicity, enumerate circulating endothelial cells (CECs) as an angiogenesis biomarker, and analyze the effect of treatment on CYP3A4-metabolized steroids.Results: 0/3 patients in cohort 1 (200mg BID) and 0/3 in cohort 2 (400mg BID) had dose-limiting toxicities in cycle 1. Thus, our recommended Phase II dose of SOR was 400 mg BID. Interim analysis of the first 12 patients showed &amp;gt;30% CBR, allowing for continued accrual to planned 35 patients. All patients had ECOG PS of 0-2. The median age was 55 years. Among 35 enrolled patients, 5 had stable disease for &amp;gt; 24 weeks, 2 had durable PR &amp;gt; 6 months, and 19 had progressive disease before 6 months. 8 patients were not response-evaluable. 1 patient on active therapy is too early to evaluate response. Clinical benefit rate is 20%. Adverse events (AEs) were generally Grade 1/2. The most common AEs (all; Grade 3/4) were fatigue (66%; 14%), diarrhea (54%; 6%), nausea/vomiting (60%; 9%), and skin rash of any kind (66%; 43%) including hand-foot syndrome (57%; 34%). G3/4 hypertension occurred in 11%. Preliminary analysis suggests that decrease in CECs from baseline to 1 week after treatment predicts for a response. Correlative science analyses are ongoing.Conclusions: The combination of SOR and ANT in patients with ER/PR+ AI-resistant MBC demonstrated an encouraging 20% CBR and is worthy of further study. A decrease in CECs appears to predict response. Toxicity with 400 mg po bid SOR occurred frequently but was manageable with dose reductions. Given the negligible activity of single-agent SOR in MBC, we believe that the benefit may be attributable to the restoration of sensitivity to AIs through inhibition of the Ras-Raf-MAPK pathway. Supported Patient for Progress Award 3 P30CA051008-15S3 and Sorafenib provided by CTEP-NCI. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3090.
AB1232 Mean platelet volume in patients with familial mediterranean fever:
Authors: S. Senel, S. Sahin, H. Ataseven, I. Yalcin
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease which is characterized by recurrent attacks of fever and peritonitis, pleuritis, arthritis, or erysipelas-like skin disease.There are very limited study in the literature about mean platelet volume (MPV) levels in FMF patients. <h3>Objectives</h3> We aimed to investigate levels of mean MPV during attack period and attack free periods in Familial Mediterranean fever (FMF) patients and to compare with healthy controls. <h3>Methods</h3> The study consisted of 16 FMF patients during an attack, 51 FMF patients in attack-free period and 75 healthy controls. Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, platelet count, and MPV levels were retrospectively recorded from patient files. <h3>Results</h3> At the end of the study statistical analyses showed that MPV was significantly lower in FMF patients both during attack and attack-free than in healthy controls (p=0.015, p=0.016); however, there was no difference among during attack and attack-free patients (p=0.279). All results were shown in Table 1. <h3>Conclusions</h3> We found that the MPV levels were significantly lower in the FMF group than in healthy controls. Our results suggest that patients with FMF have not an increased platelet activation. It was conculed that the lower MPV levels were an expected result of secondary thrombocytosis in FMF patients. <h3>Disclosure of Interest</h3> None Declared
P118 Quantity And Quality Of Referrals To Pulmonary Rehabilitation From Primary Care Following Inclusion In The Quality And Outcomes Framework (qof) In Wales
Authors: J. Ayling-Smith, M. Owen, J. Byers, D. Menzies
Journal: Thorax (2014)

<h3>Introduction</h3> Referring suitable patients for Pulmonary Rehabilitation (PR) has formed part of the Quality and Outcomes Framework (QOF) reward for General Practitioners (GPs) in Wales since April 2013. Patients with Chronic Obstructive Pulmonary Disease (COPD) that have a Medical Research Council (MRC) dyspnoea score of 3 or above, or those with an MRC score of 2 and recently discharged from hospital for COPD are eligible. We sought to determine the impact of this change on the referral pattern to our PR programme, which traditionally had only accepted referrals from secondary care respiratory consultants. <h3>Methods</h3> A standardised form was prospectively designed and distributed to enable primary care providers to refer suitable patients to the PR programme. Data on patient demographics, respiratory diagnosis, co-morbid conditions, MRC dyspnoea score, exacerbation frequency and current medication were collected. Referring GPs were also asked to provide recent spirometry values for patients that were referred. An assessment was made based on the information provided as to whether the patient could be listed immediately for pulmonary rehabilitation, whether further assessment was required, or whether the referral was inappropriate. <h3>Results</h3> A sample of 250 GP referral forms out of a total of 545 were evaluated of which 51% of patients were male and the mean age was 69 years (range 31–90). 40.8% of GP referrals could be listed immediately for PR, 34.8% of referrals needed further assessment and 24.4% were inappropriate. 22.4% of all patients referred did not have COPD based on the spirometry results supplied. Compared with the baseline referral rate to PR from secondary care consultants, the rate of referral from GPs showed a sharp increase, particularly toward the end of the financial year (difference in slope -0.77 (95% CI -2.16 to 0.61) <i>versus</i> 9.53 (6.03 to 13.03), p &lt; 0.0001) [Figure]. 36.8% of patients were found to be on off-label inhaled therapy for COPD. <h3>Conclusion</h3> The number of referrals to PR increased significantly following inclusion in QOF. The majority of the referrals from GPs either require further evaluation or are inappropriate. The spirometry data suggests there is a high misdiagnosis rate of COPD in primary care.
<i>Ex vivo</i> blood stimulation assay as a translational research tool in the development of the ticilimumab (CP-675,206)
Authors: R. Millham, D. Pavlov, P. Canniff, D. Guyot, D. Hanson, A. Ribas, L. H. Camacho, J. Gomez-Navarro
Journal: Journal of Clinical Oncology (2006)

2542 Background: Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4) is an activation-induced T lymphocyte negative costimulatory receptor which down-regulates cellular immune responses. CTLA4 blockade may break peripheral immunological tolerance, leading to an effective immune response to cancer. Tools for assessing the effects of such a blockade are limited, as CTLA4 is not constitutively expressed on circulating T cells, and because activated lymphocytes are difficult to access in vivo. Therefore, we have employed ex vivo blood stimulation assays to define pharmacodynamic properties of the anti-CTLA4 antibody, ticilimumab. Methods: Ex vivo blood stimulation assays employed staphylococcal enterotoxin A (SEA) to stimulate isolated peripheral blood mononuclear cells (PBMC) or whole blood. Stimulation was monitored by production of interleukin 2 (IL-2). This assay was used preclinically to predict in vivo responses in animal models and in samples from cancer patients, as a batch release assay for production runs of ticilimumab, and clinically as a pharmacodynamic measurement in clinical trials of ticilimumab. Results: Screening experiments using the SEA assay allowed us to identify the lead candidate mAb with optimal CTLA4 blockade activity, ticilimumab. Dose-dependent increases in IL-2 production were observed in PBMC and whole blood samples up to an in vitro concentration of 100 ug/mL of ticilimumab, with 10 ug/mL identified as the minimum predicted efficacious concentration (Ceff). This functional potency assay was adapted for qualification of production lots of ticilimumab. Whole blood taken from cynomolgus monkeys dosed with ticilimumab demonstrated significant enhancement of IL-2 production at the same magnitude observed in in vitro experiments. Additionally, longitudinal samples taken from healthy volunteers and cancer patients suggested that an enhancement of 2.8 fold would be indicative of a pharmacodynamic effect of ticilimumab. Conclusions: The SEA assay provides a functional assessment of ticilimumab activity and can be used to guide the clinical development of this agent. Our data suggest that T cell reactivity is enhanced in the presence of ticilimumab in vitro, in primate models and in humans. [Table: see text]
ELEVATED GALECTIN-3 DOES NOT PREDICT BENEFIT FROM MINERALOCORTICOID RECEPTOR ANTAGONIST USE IN PATIENTS WITH CHRONIC HEART FAILURE DUE TO LEFT VENTRICULAR SYSTOLIC DYSFUNCTION
Authors: Parul U. Gandhi, Shweta Motiwala, Arianna Belcher, Hanna Gaggin, Rory Weiner, Aaron Baggish, Mona Fiuzat, Hans-Peter Brunner-La Rocca, James Januzzi
Journal: Journal of the American College of Cardiology (2015)
Abstract 3453: SPARC overexpression inhibits cell proliferation in neuroblastoma and is partly mediated by tumor suppressor protein PTEN and AKT
Authors: Praveen Bhoopathi, Bharathi Gorantla, G.S. Sailaja, Christopher S. Gondi, Meena Gujrati, Jeffrey D. Klopfenstein, Jasti S. Rao
Journal: Cancer Research (2012)

Abstract Secreted protein acidic and rich in cysteine (SPARC) is also known as BM-40 or Osteonectin a multi-functional protein modulating cell-cell and cell-matrix interactions. In cancer, SPARC is not only linked with a highly aggressive phenotype, but it also acts as a tumor suppressor. In the present study, we sought to characterize the function of SPARC and its role in sensitizing neuroblastoma cells to radio-therapy. SPARC overexpression in neuroblastoma cells inhibited cell proliferation in vitro. Additionally, SPARC overexpression significantly suppressed the activity of AKT and this suppression was accompanied by an increase in the tumor suppressor protein PTEN both in vitro and in vivo. Restoration of neuroblastoma cell radio-sensitivity was achieved by overexpression of SPARC in neuroblastoma cells in vitro and in vivo. To confirm the role of the AKT in proliferation inhibited by SPARC overexpression, we transfected neuroblastoma cells with a plasmid vector carrying myr-AKT. AKT overexpression reversed SPARC-mediated PTEN and increased proliferation of neuroblastoma cells in vitro. PTEN overexpression in parallel with SPARC siRNA resulted in decreased AKT phosphorylation and proliferation in vitro. Taken together, these results establish SPARC as an effector of AKT-PTEN-mediated inhibition of proliferation in neuroblastoma in vitro and in vivo. 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 3453. doi:1538-7445.AM2012-3453
Abstract 409: <i>In vitro</i> and <i>in vivo</i> characterization of protein biomarkers of metastasis in melanoma.
Authors: Wen-Rong Lie, Michelle Becker-Hapak, Megan Chan, James Graham, Jehangir Mistry, Gerald Linette, Beatriz Carreno
Journal: Cancer Research (2013)

Abstract Metastasis is a major cause of death in cancer patients. We report here the use of a multiplex proteomic analysis approach to in vitro and in vivo identify biomarkers involved in melanoma invasion/metastasis. An in vitro quantitative profile of the secretome (&amp;gt;200 proteins) was done on non-metastatic melanoma cell lines (A375, LH, M14, DM.6, Lox, and WUmel19) and their metastatic RhoC-expressing counterparts (A375-RhoC, LH-RhoC, M14-RhoC, DM.6-RhoC, Lox-RhoC, and WUmel19-RhoC). A heat map cluster analysis was performed to characterize protein expression levels on metastatic vs. the non-metastatic melanoma cells and identify secreted markers with significantly altered expression that may be involved in tumor invasion, angiogenesis, and metastasis. An in vivo characterization, using an animal model of human melanoma pulmonary metastasis, has identified differential expression of tissue and circulating protein biomarkers in tumor and sera, respectively. Moreover, use of species-specific assays has allowed us to dissect the contribution of stroma (mouse) and tumor (human). Increased expression of a panel of markers, including IL-8, PLGF, FGF-2, follistatin, MMP-1, MMP-9, TIMP-1, TIMP-2, GDF15, NSE, OPN, and MIF was detected in vivo in both tumor and sera, indicating their roles in inducing angiogenesis, tumor invasion and metastasis. Cell signaling pathway multiplex analyses revealed the activation of PI3K/mTOR pathway in the tumor. Elevated levels of phosphorylated targets of PI3K/mTOR pathway, p70S6K (pT412), GSK3α (pS21), GSK3β (pS9), RPS6 (pS235/236), TSC2 (pS939) and mTOR (pS2448) were detected in the pulmonary tumor metastasis. Hence this human melanoma pulmonary metastasis model may prove to be a useful animal model for studying the actions of PI3K/mTOR inhibitors in melanoma metastasis. Altogether, these in vitro and in vivo studies using multiplex proteomic analysis may assist in the discovery of biomarkers and therapeutic targets for human melanoma interventions. Citation Format: Wen-Rong Lie, Michelle Becker-Hapak, Megan Chan, James Graham, Jehangir Mistry, Gerald Linette, Beatriz Carreno. In vitro and in vivo characterization of protein biomarkers of metastasis in melanoma. [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 409. doi:10.1158/1538-7445.AM2013-409
Cerebral Edema with Irreversible Coma in Severe Diabetic Ketoacidosis
Authors: Eusebio Young, Robert F. Bradley
Journal: New England Journal of Medicine (1967)

THE number of deaths from severe diabetic acidosis has been significantly reduced in recent years with adequate insulin treatment and a better understanding of fluid and electrolyte balance. Experience at the Joslin Clinic has indicated a mortality of 3 to 5 per cent.1 However, deaths in 12 to 15 per cent of cases reported by those skilled in the treatment of diabetic ketoacidosis2 3 4 5 indicate a significantly higher mortality generally prevailing in most hospitals. Ordinarily, unless diagnosed late or handled inadequately, severe diabetic acidosis and coma are not fatal, and many of the deaths that continue to occur are related to . . .
The SH2 domain-containing protein tyrosine phosphatase SHP-1 is induced by granulocyte colony-stimulating factor (G-CSF) and modulates signaling from the G-CSF receptor
Authors: AC Ward, SPMA Oomen, L Smith, J Gits, D van Leeuwen, AA Soede-Bobok, CAJ Erpelinck-Verschueren, T Yi, IP Touw
Journal: Leukemia (2000)
403 MESENCHYMAL STEM CELLS EXPRESSING IFITM3 CAN CAUSE THE INHIBITION OF HEPATITIS B VIRUS REPLICATION IN VITRO
Authors: Y.-B. Zheng, B.-L. Lin, C.-S. Lin, J. Liu, Z.-B. Wu, Y.-J. Su, H.-L. He, Z.-L. Gao
Journal: Journal of Hepatology (2013)
DIRECT CELL CONTACT BETWEEN BRAIN ENDOTHELIAL CELLS AND GLIOMA STEM CELLS PROMOTES ENDOTHELIAL CELL MIGRATION
Authors: C. L. Gladson, M. E. Burgett, J. D. Lathia, P. Roth, P. Huang, A. Vasanji, M. Li, S. Bao, A. Nowacki, J. N. RIch, M. Weller
Journal: Neuro-Oncology (2014)

BACKGROUND: A histologic characteristic of glioblastoma tumors (GBM) is angiogenesis, which requires endothelial cell (EC) sprouting and migration. This is thought to be facilitated by signals in a specialized microenvironment, the perivascular niche, where glioma stem cells (GSC) reside in proximity to ECs. The goal of this study was to determine whether ECs and GSCs directly interact, the mechanism by which this occurs, and the effect on EC signaling and function. METHODS: We utilized multi-label immunofluorescence of GBM tissue and of co-cultured ECs and GSCs to evaluate the proximity of ECs to GSCs and effect of this interaction on signaling, respectively. Cell-cell binding assays, two-photon laser scanning microscopy of cells injected into brain slices in organotypic culture, live-video microscopy of 2D-migration analyzed by Cell Tracker and 3D-chemotactic migration assessed the mechanism of EC-GSC interaction and EC motility. In vivo effects of inhibiting EC interaction with GSCs were evaluated in an orthotopic mouse model of GBM. RESULTS: We found that GSCs were largely localized in very close proximity to ECs in GBM biopsies and bound to normal brain or GBM-derived ECs on Matrigel promoting EC network-formation. In multiple assays, we found that ECs and GSCs directly interact through a mechanism mediated by integrin αvβ3 on ECs binding the RGD-peptide in extracellular L1CAM on GSCs. Importantly, the direct interaction of ECs with GSCs increased the velocity and directional 2D motility of ECs, as well as the chemotactic migration of ECs. A cyclic RGD-peptide, neutralizing antibodies to integrin αvβ3 or L1CAM, and the downregulation of β3 on ECs or of L1CAM on GSCs all inhibited the EC-GSC direct interaction and the increased EC motility. Signaling studies showed that the EC-GSC interaction increased activation of integrin αvβ3, ERK and JNK in ECs and increased nuclear Akt in GSCs, suggesting bidirectional signaling. Soluble L1CAM also activated integrin αvβ3 on ECs. Cyclic RGD-peptide (Cilengitide) treatment of established mouse GBM tumors reduced the percent of Sox2-positive cells within 25-microns of vessels from 65%-to-29% and the percent Sox2-positive cells within 10-microns of vessels from 30%-to-17%. The ratio of Sox2-postiive cells/vessel was unaltered. CONCLUSIONS: These data suggest that (i) GSCs can promote EC motility and thereby angiogenesis through direct contact with ECs, and indicate a role for GSC L1CAM and EC αvβ3 in this interaction; and (ii) Soluble L1CAM activates integrin αvβ3 on ECs, thus circulating soluble L1CAM could interfere with the therapeutic effects of Cilengitide in patients. SECONDARY CATEGORY: Preclinical Experimental Therapeutics.