tbuckley/cabot-search huggingface dataset:
Increased Platelet Catecholamine Content in Pheochromocytoma
Authors: Andrew J. Zweifler, Stevo Julius
Journal: New England Journal of Medicine (1982)

Platelet catecholamine content was determined by radioenzymatic assay in 16 patients with elevated plasma norepinephrine or epinephrine or both and a clinical picture suggesting pheochromocytoma. Twenty-two normal subjects served as controls. Pheochromocytoma was documented in 10 patients, all of whom had markedly elevated platelet catecholamines. The other six patients had no tumor, and their platelet catecholamine levels were normal. Platelet catecholamines tended to return to normal more slowly than plasma catecholamines after removal of the pheochromocytoma, suggesting that platelets were rich in stored catecholamines. Determination of platelet catecholamine content is a helpful aid to the diagnosis of pheochromocytoma in patients with suggestive but not diagnostic elevations of the plasma catecholamine concentration.
AB0816 Efficacy of biological agents in the treatment of idiopathic retroperitoneal fibrosis
Authors: M. Catanoso, L. Magnani, L. Spaggiari, N. Pipitone, A. Caruso, O. Addimanda, R. Meliconi, L. Pulsatelli, A. Versari, L. Boiardi, A. Vaglio, P. Pattacini, C. Salvarani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Glucocorticoids (GCs) are the most used drugs for the treatment of idiopathic retroperitoneal fibrosis (IRF).Several steroid-sparing agents, including immunodepressants and tamoxifen, have been used with varying success. However, some patients are resistant to these therapies and valuable medical treatments are not available.The aim of this study was to assess the efficacy and safety of the anti-IL-6 receptor (IL-6R) antibody tocilizumab (TCZ) in patients with IRF. <h3>Methods</h3> Two patients received monthly TCZ infusions (8 mg/kg bodyweight) for six consecutive months.One of the patients treated with TCZ was previously unsuccessfully treated with IFX and abatacept and one patient was naive to biological agents.Disease activity and drug tolerability were assessed every month clinically and by laboratory tests such as ESR, CRP, IL-6, and the IL-6 soluble receptor (sIL-6R).18F-fluorodeoxyglucose PET (PET/CT) and abdominal Compurerized Tomography(CT)-scans were used for monitoring disease activity and treatment response. <h3>Results</h3> All two patients had a satisfactory clinical and laboratory response with a significant improvement of CT and PET findings.A reduction of retroperitoneal mass greater than 25% was observed in all patients. Remission maintenance therapy with MTX (20 mg/weekly)was started in all two patients. No serious adverse events were noted <h3>Conclusions</h3> TCZ is potentially effective treatments for patients with IRF that warrants evaluation in randomized trials. <h3>Disclosure of Interest</h3> None Declared
Abstract 4244: TTAC-0001, fully human anti-VEGFR2/KDR neutralizing antibody blocks tumor angiogenesis and tumor growth
Authors: Weon Sup Lee, Bo-Jeong Pyun, Sung-Woo Kim, Sang Ryeol Shim, Hyeon-Mi Yoo, Keunhee Oh, Dong-Sup Lee, Ji-Young Yoo, Chae-Ok Yun, Young-Guen Kwon, Sang Hoon Lee, Jin-San Yoo
Journal: Cancer Research (2011)

Abstract Angiogenesis, the recruitment of new blood vessels is a crucial mechanism required for both tumor growth and metastasis. Vascular endothelial growth factor (VEGF) and its receptors, particularly VEGF receptor 2 (VEGFR2, or kinase insert domain-containing receptor, KDR), play a critical role in tumor-associated angiogenesis. Monoclonal antibodies (mAb), due to their high specificity towards a given target, represent a unique class of novel therapeutics as angiogenesis inhibitors. We developed TTAC-0001, anti-KDR antibody from a fully human naïve single chain variable fragment (ScFv) phage library. Interestingly, TTAC-0001 displayed cross reactivity against murine homologue, Flk-1, which allows us to evaluate the anti-tumor efficacy in various in vivo models. TTAC-0001 inhibits VEGF-mediated proliferation and migration. In HUVEC, TTAC-0001 inhibited the phosphorylation of VEGFR2/KDR and ERK mediated by VEGF. TTAC-0001 inhibited VEGF-mediated sprouting endothelial cells from rat aortic rings and showed a potent anti-angiogenic activity in VEGF-mediated matrigel model in nude mice. Further in vivo anti-tumor efficacy of TTAC-0001 was seen in the xenografts of A549 (lung) and HCT116 (colorectal) human cancer. These changes were accompanied by the inhibition of microvessel density and induction of apoptosis in the tumors. In summary, our data indicates that TTAC-0001 blocks the binding of VEGF to VEGFR2/KDR and inhibits VEGFR-induced angiogenesis. Therefore, this data strongly supports for the further development of TTAC-0001 as an anti-cancer agent (This study was supported by grants of the Korea Healthcare technology R&amp;D Project, Ministry for Health &amp; Welfare Affairs (A092255 and A040016) and Advanced Medi-cluster R&amp;D Project, Daejeon TechnoPark, Republic of Korea). 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 4244. doi:10.1158/1538-7445.AM2011-4244
Response to Interferon Alfa-2b in a Patient with Systemic Mastocytosis
Authors: Hanneke C. Kluin-Nelemans, Joop H. Jansen, Henk Breukelman, Bert G Wolthers, Philip M. Kluin, Herman M. Kroon, Roel Willemze
Journal: New England Journal of Medicine (1992)

IN systemic mastocytosis, an abnormal proliferation of mast cells infiltrates the skin, bone marrow, spleen, liver, and lymph nodes.1 2 3 The release of mast-cell mediators such as histamine causes systemic attacks, with flushing, itching, headache, gastrointestinal symptoms, and even vascular collapse with syncope.1 Although the life expectancy of most patients is good, some have a malignant form of the disease, aggressive systemic mast-cell disease, in which there is marked infiltration of organs by mast cells and a rapidly progressive downhill course.1 The presence of leukemic circulating mast cells indicates a particularly grave prognosis.1 , 4 , 5 So far, there is no effective treatment for . . .
Abstract 4352: Using human neural stem cells to model pediatric high grade gliomas: The role of p53, c-myc, and EGFRvIII in neoplastic transformation
Authors: Eric H. Raabe, Jarek Maciaczyk, Ulf Kahlert, Guido Nikkhah, Charles Eberhart
Journal: Cancer Research (2010)

Abstract Brain tumors are a heterogeneous group of cancers that can arise at multiple locations in the central nervous system. Some brain tumors are restricted to specific anatomical sites, such as medulloblastoma, which is found only in the cerebellum. In the context of this heterogeneity, there are common molecular pathways which are altered across different types of brain tumors. Some of these molecular lesions include inactivation of tumor suppressors such as p53, overexpression of pro-proliferative factors such as c-myc, and alteration of cytokine pathways involving PDGF and EGF. We have isolated neural stem and progenitor cells from multiple sites in the developing human brain, including spinal cord, brain stem, cerebellum, thalamus, and cerebral cortex. These cells can be grown as neurospheres in long term culture, and can differentiate into neurons, astrocytes and oligodendrocytes. To test the hypothesis that these human neurosphere cells can give rise to brain tumors, we infected them with lentivirus encoding hTERT as well as dominant-negative p53, c-myc, and EGFRvIII. The resultant clones derived from cortex, brain stem and spinal cord grow at an increased rate compared to control GFP-infected cells. Interestingly, thalamus-derived cells in the initial analysis do not proliferate rapidly in response to dominant negative p53 and c-myc overexpression, highlighting the potential differences in neural stem and progenitor cell response to oncogenic stimuli. Dominant negative p53 and c-myc overexpressing cells maintain an ability to differentiate in vitro, similar to that observed in human glioblastoma neurosphere lines. Experiments to test the in vitro clonogenic potential and in vivo engraftment of control and infected cells are pending. Our studies suggest that, in contrast to some previous reports, human neural precursor cells can be transformed. They also form the basis for future experiments aimed at creating genetically and pathologically relevant models for pediatric brain tumors. 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 4352.
S98 Vitamin D deficiency increases bacterial load in a murine model of sepsis-induced lung injury: Abstract S98 Table 1.
Authors: D Parekh, RCA Dancer, S Lax, GD Perkins, DR Thickett
Journal: Thorax (2013)

<h3>Introduction</h3> We have previously shown that patients with Acute Lung Injury (ALI) are severely vitamin D deficient. Several studies have reported a high prevalence of vitamin D deficiency in critically ill patients with sepsis, associated with increased morbidity and mortality but whether this is cause or effect is unknown. Bacteraemic sepsis is more common in the winter months when vitamin D levels are lowest. The purpose of this study was to investigate the local and systemic effects of vitamin D deficiency in a murine model of sepsis-induced lung injury where we can predictably time the initiating insult. <h3>Methods</h3> We fed 8 wild-type C57Bl/6 mice a diet completely devoid of vitamin D for 6 weeks to induce severe vitamin D deficiency (9 nmol/l) and compared to 7 mice fed a vitamin D sufficient diet (42 nmol/l). Caecal ligation and puncture (CLP) was used to establish sepsis. Animals were culled 16h after CLP and blood, peritoneal lavage fluid (PLF) and bronchoalveloar lavage fluid (BALF) were collected. Cell infiltrates were assessed by flow cytometry. Fluid protein levels were measured and tissue protein permeability index (PPI) was calculated as the ratio between fluid and serum protein. Bacterial load was evaluated as colony-forming units (CFU) after 24h incubation on appropriate media. <h3>Results</h3> Vitamin D deficient mice had increased bacterial load in BALF, blood and PLF compared to dietary sufficient mice. BALF protein permeability index was higher in deficient compared to sufficient mice but there was no difference in cell numbers recruited to the lung. PLF protein permeability index was also increased in the deficient group compared to sufficient mice with an associated significant increase in neutrophils recruited to the peritoneum. (See Table 1) <h3>Conclusion</h3> Vitamin D deficiency significantly increases the bacterial load both systemically, locally and within the lung in a murine model of peritonitis. This is associated with an increase in tissue permeability locally and within the lung. These data support pre-existing vitamin D deficiency as a determinant of the severity of bacteraemic sepsis and may account for some of the seasonal variations observed in the incidence of sepsis.
Uncertain Value of Electronic Fetal Monitoring in Predicting Cerebral Palsy
Authors: Karin B. Nelson, James M. Dambrosia, Tricia Y. Ting, Judith K. Grether
Journal: New England Journal of Medicine (1996)

Electronic monitoring of the fetal heart rate is commonly performed, in part to detect hypoxia during delivery that may result in brain injury. It is not known whether specific abnormalities on electronic fetal monitoring are related to the risk of cerebral palsy.
A Man with Bizarre Behavior
Authors: Chevon M. Rariy, Alison Schram, Daniel T. Ruan, Anand Vaidya, Erik Alexander
Journal: New England Journal of Medicine (2015)

A 24-year-old man was brought to the emergency department by ambulance after exhibiting abnormal and agitated behavior. On presentation, he was wearing only underwear and yelling "I am God!" repeatedly. He was alert, awake, and talkative but was not responsive to direct questioning. Although his speech was fluent, its content was illogical and was not directed toward . . .
Case 30-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, T. Edward Bynum, Atul K. Bhan
Journal: New England Journal of Medicine (1989)

Presentation of CaseA 52-year-old man was admitted to the hospital because of esophageal varices and repeated bouts of upper gastrointestinal bleeding.There was a 10-year history of vague pain in the right upper abdominal quadrant. Six years before entry the patient experienced the first bout of upper gastrointestinal bleeding. Four years before admission an upper gastrointestinal series, performed elsewhere, was reported to show extensive esophageal and gastric varices, without ulceration. Two years later massive hematemesis recurred and required the transfusion of 19 units of blood.Fifteen months before admission evaluation elsewhere showed that the spleen descended 6 cm below . . .
THU0163 Disease Flares Predict the Change to Second Line Therapy in Rheumatoid Arthritis: 9-Year Data from a Longitudinal Observational Study
Authors: I. Ancuta, C. Codreanu, R. Ionescu, M. Parvu, M. Bojinca
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The role of disease worsening or flares in taking important clinical decisions, such as dose adjustments or treatment change, is poorly understood in patients suffering from severe RA treated with TNF inhibitors over long periods of time. <h3>Objectives</h3> To determine whether the prevalence of flare episodes can predict the response to anti-TNF treatment over time and the change to second line therapy. <h3>Methods</h3> In this longitudinal, observational, population-based, cohort study we included a total of 400 patients. Data were retrieved from the National Health Insurance House (NHIH) database (2002-2011). Flare events were defined according to OMERACT criteria as increase in disease activity score DAS28 &gt;3.2 or &gt;0.6 if DAS28 &gt;3.2. Prevalence of flare episodes, DAS28 response rates and EULAR response rates were calculated every six months. <h3>Results</h3> In our analysis, 379 (94.5%) patients presented 672 flare episodes (prevalence 168% in the analysed population). <h3>Conclusions</h3> In current clinical practice in Romania, a single flare episode in patients with a MDA should prompt change to second line therapy, including biological agents with other mechanisms. Our real life results, based on data collected before 2012, support OMERACT flares criteria and ACR/EULAR recommendations, emphasizing strict patient evaluation and tight control in the first 1-3 months after anti-TNF treatment initiation. <h3>Disclosure of Interest</h3> None Declared
Abstract 4881: Induction of Bim by the BRAF inhibitor PLX4720 sensitizes human melanoma cells to the BH3 mimetic ABT-737
Authors: David Wroblewski, Xu Dong Zhang, Peter Hersey
Journal: Cancer Research (2012)

Abstract Once melanoma has metastasized to distant sites it has proved difficult to treat by a variety of chemotherapeutic and biological agents. Significant advances have been made in identifying subgroups of patients with activating mutations in signalling pathway proteins. In particular, the finding that approximately 50% of melanoma have V600E mutations in the BRAF serine/threonine kinase has resulted in the generation of a number of new drugs which target the mutated active form of BRAF. One of these drugs, Vemurafenib (PLX4032/RG704) has shown significant promise in prolonging survival compared to standard chemotherapy, however reports of patient relapse has prompted investigation into means of overcoming acquired resistance to the agent. We report here that efficacy of the PLX4032 analogue, PLX4720, is greatly enhanced by co-treatment with the BH3 mimetic, ABT-737. Treatment with either agent is able to induce apoptosis in melanoma cells, however the kinetics are typically slow, with cell death occurring 48 or 72 hours post treatment. In this study, while either agent was largely ineffective as a single treatment 24 hours following treatment, addition of the combination of drugs rapidly induced significant killing. We show that apoptosis was caspase-dependent, in that inhibition of caspase activation almost totally blocked induction of cell death by the combination of agents. Apoptosis was also associated with activation of the intrinsic apoptotic pathway, with reduction of mitochondrial membrane potential and activation of caspase-9. Exposure of melanoma cells to PLX4720 rapidly decreased phosphorylation of the pro-apoptotic BH3-only protein Bim, resulting in strong upregulation as early as 6 hours after addition of the compound. Strong upregulation of Bim was shown by RNAi knockdown to play an important role in sensitizing cells to co-treatment with ABT-737, by assisting in the inhibition of anti-apoptotic Bcl-2 family proteins. Further, the combination of agents induced significant levels of apoptosis in melanoma cells derived from patients harbouring the BRAFV600E mutation. Collectively, these results show that the BRAF inhibitor PLX4720 sensitizes melanoma cells to apoptosis by the BH3 mimetic ABT-737 in a Bim- and caspase-dependent manner. Additionally, these studies identify a potential clinical application for BH3 mimetics in overcoming resistance of melanoma to treatment with BRAF inhibitors, increasing efficacy of this class of agent and improving patient outcomes. 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 4881. doi:1538-7445.AM2012-4881
MYOCARDIAL PERFUSION NETWORK ANALYSIS BY CARDIAC COMPUTED TOMOGRAPHY AS A NOVEL METRIC FOR IDENTIFICATION OF HIGH-GRADE ANATOMIC CORONARY STENOSIS
Authors: Guanglei Xiong, Deeksha Kola, Kimberly Elmore, Ran Heo, Quynh Truong, Millie Gomez, James Min
Journal: Journal of the American College of Cardiology (2015)
Intestinal obstruction caused by giant filiform polyposis in a patient with normal colon
Authors: G. Mavrogenis, P. Ngendahayo, P. Kisoka, M. Nicholas, E. Kovács, Y. Hoebeke, P. Warzée
Journal: Endoscopy (2013)

A 31-year-old patient with no previous history of inflammatory bowel disease (IBD) underwent further evaluation for recurrent episodes of intestinal obstruction. Abdominal computed tomography revealed thickening of the wall of the ascending colon and dilated small-bowel loops ([Fig. 1]). Colonoscopy disclosed a large polypoid mass with fingerlike projections in the right colon ([Fig. 2]). Progression of the endoscope beyond this point was not possible. Biopsies were negative for malignancy. Prompted by the suspicious endoscopic appearance of the lesion and the signs of intestinal obstruction, a right-sided hemicolectomy was carried out. The resected specimen included a mass with multiple clustered polyps with several branches that almost completely obliterated the lumen of the colon ([Fig. 3]). Microscopic examination was consistent with giant filiform polyposis ([Fig. 4]). The nonpolypoid mucosa of the terminal ileum and right colon was normal.
Abstract 421: Epidermal growth factor-like repeats of tenascin C alter melanoma cell migration both directly and through alteration of the ECM
Authors: Jelena Grahovac, Alan Wells
Journal: Cancer Research (2011)

Abstract In melanoma, the most aggressive type of skin cancer, invasion through the extracellular matrix (ECM) is a harbinger of dissemination and mortality. Highly upregulated in both primary invasive and metastatic melanoma is tenascin C (TNC), a hexameric ECM protein with a multidomain structure composed of the globular N-terminal domain, 14.5 epidermal growth factor (EGF)-like repeats, fibronectin-III like repeats and the C-terminal globular fibrinogen-like domain. Our group previously showed that the EGF-like repeats of TNC are able to bind the EGF receptor (EGFR) with μM affinity and preferentially activate the motogenic signaling cascades. Both normal melanocytes and melanoma cells migrate faster on surfaces coated with TNC. Therefore, we hypothesize that the increased levels of TNC in melanomas promote tumor cell migration and invasion heralding dissemination through enhanced EGFR signaling. We expressed EGF-like repeats of TNC (TNC-EGFL) in melanoma cell lines already expressing endogenous TNC and observed change in the cell morphology, and more importantly a prominent anti-adhesive phenotype. TNC-EGFL expressing cells attached with a four-hour lag compared to parental cell lines and detached to a greater extent in inverted centrifugation adhesion assays. This was not due to decreased viability of TNC-EGFL expressing cells as determined by dye exclusion assay. As this phenotype could not be reverted by adding anti-EGFR antibody, we speculate that EGFR signaling might be intracellular. In two-dimensional migration assays, TNC-EGFL expressing cells closed a gap more slowly, possibly due to inability to properly attach during migration, emphasizing the need of concerted action of different TNC domains in regulating migration. On the other hand, quantitative PCR array analysis of a panel of ECM and adhesion molecules revealed changes in matrix metalloproteinase (MMP) expression, specifically MMP-2, MMP-9 and MMP-14, and increase in TGF β1 expression, proteins associated with melanoma invasiveness and vasculogenic mimicry. These results imply that TNC-EGFL repeats are involved in melanoma invasion both by directly influencing cell migration and indirectly by altering the tumor microenvironment and may have implications for development of anti tumor therapies directed at the extracellular matrix. 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 421. doi:10.1158/1538-7445.AM2011-421