tbuckley/cabot-search huggingface dataset:
CS-08 * SONIC HEDGEHOG SIGNALING PROTECTS ATOH1 FROM DEGRADATION MEDIATED BY THE HECT DOMAIN E3 UBIQUITIN LIGASE HUWE1 IN CEREBELLAR GRANULE NEURON PROGENITORS
Authors: A. Forget, L. Bihannic, S. Cigna, C. Lefevre, M. Remke, M. Barnat, S. Dodier, H. Shirvani, A. Mercier, A. Mensah, M. Garcia, S. Humbert, M. D. Taylor, A. Lasorella, O. Ayrault
Journal: Neuro-Oncology (2014)

Cerebellar development requires a balance between several biological processes including proliferation, differentiation and migration. The pro-neural basic helix-loop-helix transcription factor Atoh1 was shown to be a key player controlling the formation of granule neuron progenitors (GNPs). Its uncontrolled levels in collaboration with Sonic Hedgehog (SHH) activation are critical for medulloblastoma (MB) formation, a devastating pediatric tumor that originates from the cerebellum. Because Atoh1 acts as a lineage dependency transcription factor in MB, mechanisms controlling Atoh1 expression are keen interest in the field. However, how this master transcription factor is regulated has remained poorly understood. In our study, we dissected the machinery that regulates Atoh1 in GNPs and in MB. We first identified two phosphorylation sites that regulate Atoh1 stability and function in GNPs. Second, combining tandem affinity purification with an Atoh1 phospho-deficient mutant and multidimensional protein identification technology analysis, we identified the E3 ubiquitin ligase Huwe1 as Atoh1 binding partner. We showed that Atoh1 physically interacted with Huwe1 in a phospho-dependent manner in GNPs, mediating its ubiquitylation whereas Cre-mediated deletion of Huwe1 from postnatal GNPs increased Atoh1 protein levels. Next, we uncovered that SHH regulates Atoh1 stability by preventing its phospho-dependent degradation by Huwe1. In the tumoral context, consistent with Atoh1 upregulation in MBs driven by SHH activation, Huwe1 was found downregulated in primary mouse tumors. In human SHH MB, low HUWE1 expression was found specifically associated with poor prognosis. Overall, our results reveal that SHH and Atoh1 contribute to a positive autoregulatory loop promoting neuronal precursor expansion. Consequently, Huwe1 alterations in SHH MB illustrate the disruption of this developmental mechanism in cancer. This crosstalk between SHH signaling and Atoh1 during cerebellar development highlights a new collaborative network that could be further targeted in MB.
Predictors of recurrence after definitive chemoradiation for anal cancer: The Cleveland Clinic experience
Authors: K. Almhanna, A. Lazaryan, S. Kalmadi, R. D. Kim, J. P. Saxton, I. Lavery, V. Foazio, E. Kay, R. Pelley
Journal: Journal of Clinical Oncology (2008)

15000 Background: Concurrent chemoradiotherapy (CRT) is the standard of care for squamous cell cancer of the anal canal (SCCA). Optimizing outcomes is likely to depend on a number of factors. Identification of factors portending treatment failure is critical. Methods: Data on patients with SCCA treated at the Cleveland Clinic were reviewed. Log-rank analysis was used to identify factors predictive of treatment failure, disease recurrence, and survival. Results: Between 9/83 and 3/07, 99 patients with SCCA were treated at our institution. Median age was 57 years. 63% were women, 98% had an ECOG score of 0–1, 53% were smokers, 29% had clinical node positive disease, and 50% had T3/4 tumors. With a median follow-up of 12.6 years, the median disease free survival (DFS) and overall survival (OS) have not been reached. 5-year DFS is 70% and 5-year OS is 72%. Significant treatment-related skin toxicity was reported in 62% of patients. 13 patients were hospitalized for neutropenic fever. Two developed TTP/HUS after mitomycin therapy. Persistent disease was more frequent in patients with N2/3 disease (vs. N0/1, p = .046). Higher ECOG performance status, interruption of radiation, T3/4 disease, N2/3 disease, and skin toxicity during treatment were each associated with significantly increased recurrence rates (all p <0.05). Patients with advanced T stage had a worse overall survival (p=0.02), while patients with BMI ≥ 25 had a better overall survival (p=0.04). Conclusions: In this series, advanced clinical stage, interruption of radiation therapy, and treatment-related skin toxicity correlate with recurrence. Trials of more aggressive locoregional and systemic therapies are warranted in high risk patients based on their clinical stage, and interventions to reduce treatment-related toxicity and unplanned treatment interruption are needed. No significant financial relationships to disclose.
ELECTROCARDIOGRAPHY AND ELECTROPHYSIOLOGY STUDIES BEFORE AND AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT AS TOOLS TO DECIDE PERMANENT PACEMAKER IMPLANTATION AND PATIENT'S MONITORING
Authors: Caroline Chong-Nguyen, Nicolas Badenco, Carole Maupain, Olivier Barthélémy, Rémi Choussat, Pascal Leprince, Françoise Hidden-Lucet, Robert Frank, Jean-Philippe Collet
Journal: Journal of the American College of Cardiology (2016)
Obstructive Hydronephrosis With I-131 MIBG Accumulation Mimicking Huge Pheochromocytoma: A Diagnostic Pitfall Found With Tc-99m MDP Imaging
Authors: PAN-FU KAO, KAI-YUAN TZEN, MIAU-JU HUANG, DONG-LING YOU
Journal: Clinical Nuclear Medicine (1996)

A case of severe obstructive hydronephrosis, which caused a false-positive I-131 MIBG scan for detection of a pheochromocytoma is reported. A huge area of persistent I-131 MIBG accumulation 72 hours after injection in the left flank region was suspected to be a huge pheochromocytoma. Combined studies with I-131 MIBG, Tc-99m MDP, Tc-99m DMSA, and Tc-99m DTPA as well as furosemide injection disclosed that the abnormal I-131 MIBG accumulation was caused by left obstructive hydronephrosis. The result was finally confirmed by intravenous pyelography and CT studies.
A Comparison of Low-Dose Heparin with Low-Molecular-Weight Heparin as Prophylaxis against Venous Thromboembolism after Major Trauma
Authors: William H. Geerts, Richard M. Jay, Karen I. Code, Erluo Chen, John Paul Szalai, Eric A. Saibil, Paul A. Hamilton
Journal: New England Journal of Medicine (1996)

Patients who have had major trauma are at very high risk for venous thromboembolism if they do not receive thromboprophylaxis. We compared low-dose heparin and a low-molecular-weight heparin with regard to efficacy and safety in a randomized clinical trial in patients with trauma.
Ipilimumab-Induced Colitis on FDG PET/CT
Authors: Ashima Lyall, Herbert Alberto Vargas, Richard D. Carvajal, Gary Ulaner
Journal: Clinical Nuclear Medicine (2012)

A 52-year-old woman with metastatic melanoma was treated with ipilimumab. After 2 cycles of treatment, she developed watery diarrhea, sweats, and chills. An FDG PET/CT study demonstrated new FDG-avid (maximum standardized uptake value 15.6) diffuse colonic wall thickening, suggestive of ipilimumab-induced colitis. The patient was treated with systemic steroids, with subsequent resolution of her symptoms. Based on the response to steroids, the diagnosis of ipilimumab-induced enterocolitis was made. Ipilimumab may cause several immune-mediated toxicities, the most common of which is enterocolitis. Physicians interpreting FDG PET/CT examinations of patients treated with ipilimumab should be aware of these FDG-avid immune-mediated toxicities.
A7.05 Baricitinib abrogates IFNγ-induced focal adhesion kinase (FAK) activation in fibroblast-like synoviocytes
Authors: T Karonitsch, C Wunrau, D Beckmann, K Dalwigk, R Byrne, B Niederreiter, A Wanivenhaus, J Holinka, C Scheinecker, G Steiner, JS Smolen, T Pap, HP Kiener
Journal: Annals of the Rheumatic Diseases (2016)

<h3></h3> While evidence implicates both the adaptive and innate immune system in rheumatoid arthritis (RA) pathogenesis, accumulating data indicate that the synovial tissue itself actively participates in the destructive inflammatory process. Specifically, resident fibroblast-like synoviocytes (FLS), together with macrophages, re-organise to form an aggressive cell mass, called pannus, which destroys the articular cartilage and the subchondral bone. The exact molecular mechanisms of synovial pannus formation, FLS expansion and invasion into adjacent tissues are not yet known. Our data strongly suggest that the T-cell derived cytokine IFNγ is involved in FLS-mediated joint destruction. Migration and invasion assays revealed increased migratory activity for IFNγ-stimulated FLS, when compared to unstimulated FLS. Further, biochemical studies showed that IFNγ promotes the migratory and invasive activity of FLS via Janus kinase 2 (JAK2) and the focal adhesion kinase (FAK), a kinase known to integrate focal adhesion turnover and thus, regulates cell migration. In detail, IFNγ stimulation of FLS distinctly resulted in the phosphorylation of FAK-Y925, a phospho-site that has recently been demonstrated to be required for FAK-mediated cell migration. siRNA knockdown of JAK2, but not JAK1, abrogated the IFNγ-induced activation of FAK. Correspondingly, baricitinib, a JAK inhibitor that is currently successfully probed in RA clinical trials, abrogated IFNγ-stimulated activation of FAK. In conclusion, our studies contribute insight into the synovial response to IFNγ and reveal JAK2 and FAK as potential targets for synoviocyte-mediated joint destruction in arthritis, especially in RA.
INCIDENCIA DE COMPLICACIONES DE LA COLONOSCOPIA EN UN PROGRAMA DE CRIBADO POBLACIONAL DE CÁNCER COLORRECTAL: ESTUDIO PROSPECTIVO MULTICÉNTRICO
Authors: E Sanabria Velazquez, A Seoane Urgorri, I Araujo, A García, L Márquez, A Pozo, A Serradesanferm, M López-Ceron, M Andreu, M Pellisé
Journal: Endoscopy (2013)

Introducción: La colonoscopia (CS) es la herramienta fundamental para la prevención del cáncer colorrectal (CCR). Se desconoce la frecuencia y la repercusión de las complicaciones de la CS de cribado poblacional. Objetivo: Evaluar la incidencia de complicaciones mayores y menores asociadas a CS de un programa de cribado poblacional basado en test inmunológico de sangre oculta en heces. Estimar su repercusión sobre el absentismo laboral. Material y Método: Estudio observacional, descriptivo, de muestreo consecutivo. Se incluyeron todos los sujetos de 2 hospitales de tercer nivel durante 6 meses. Se recogieron datos demográficos y endoscópicos. Posteriormente se realizó registro prospectivo de complicaciones menores y mayores mediante cuestionario y llamada telefónica a los 14 y 30 días del procedimiento. Se adoptó el consenso de la ASGE para la definición de complicaciones1. Resultados: En total, se reclutaron 870 sujetos, de los cuales se han analizado hasta la fecha 414 (53% varones; edad media 59,8 ± 5,6 años). Todos los procedimientos se realizaron con anestesia. El 91,3% presentó limpieza adecuada según la escala de Boston y una tasa de intubación cecal del 98,6%. Se extirparon pólipos en 71% de CS. No se registraron casos fatales. 238 sujetos (57,5%) presentaron al menos una complicación: 3 mayores (2 rectorragias que requirieron re-CS, 1 hemoperitoneo), y el resto menores, siendo las más frecuentes distensión abdominal (25,1%), dolor abdominal (23,2%) y astenia (15,0%). En el análisis univariado, únicamente se encontró una asociación significativa con el género femenino (p = 0,033). Hasta 134 pacientes (32,4%) se ausentaron de sus trabajos de 1 a 2 días extras. Conclusiones: La incidencia de complicaciones menores de la CS de cribado es considerable. El impacto de la CS de cribado sobre el absentismo laboral parece relevante. (1) Cotton PB, et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. GIE 2010.
Radon Revisited; Smokers Beware
Authors: K. L. Smigel
Journal: JNCI Journal of the National Cancer Institute (1988)

Radon Revisited; Smokers Beware Get access Kara L. Smigel Kara L. Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 16, 19 October 1988, Pages 1275–1276, https://doi.org/10.1093/jnci/80.16.1275 Published: 19 October 1988
Obstructive Jaundice: Dilated CBD, Normal PD, No stones - What then?
Authors: A George, R Ponnudurai, S Sachithanandan, G Kanagasabai, S Tan, A Abdullah, Y Chan, I Merican
Journal: Endoscopy (2006)

Objective: To analyze the aetiology of disease in patients with obstructive jaundice who present with an obstructed distal common bile duct (CBD) but normal caliber pancreatic duct (PD) but with no evidence of choledocholithiasis.
P11.09 * A NEUROLOGIC PRESENTATION OF INTRAVASCULAR LARGE B-CELL LYMPHOMA
Authors: A. F. M. R. Matas, A. S. B. T. Veiga, J. P. M. S. Gabriel, M. R. Silva
Journal: Neuro-Oncology (2014)

INTRODUCTION: Intravascular large B-cell lymphoma is a rare and fatal disease that can have central nervous system manifestations. Given its rarity and the multiplicity of presentations, diagnosis is extremely difficult. We report a case that presented with neurological manifestations and which diagnosis was made ante mortem. CASE REPORT: A 74-year-old man, with a background of hypertension and dyslipidemia was referred to our neurology department with a history of speech difficulties and walking disturbances that rapidly evolved to an acute confusional sate. Physical examination disclosed an obvious executive dysfunction, global dysphasia and gait dyspraxia. Computed tomography scan of the brain showed a right frontal paramedian subcortical hiperdensity. Further characterization with brain MRI showed that this lesion was not expansive and did not enhanced with gadolinium. On laboratory analysis there was a mild lymphopenia and increased lactate dehydrogenase and ferritin levels; erythrocyte sedimentation rate was in the normal range and the immunological and virological tests were negative. Glucocorticoids (methylprednisolone 1g, intravenous, per day, during five days) were administered, leading to some improvement in the patient's symptoms. However, the control brain MRI disclosed lesion worsening, with bihemispheric extension. The cerebrospinal fluid study was unremarkable and the anti-neuronal antibodies were negative. Control laboratory analysis revealed an increase in serum C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase (>900 IU/l), hepatic enzymes and B2-microglobulin levels. Electroencephalography was unremarkable and there was no evidence of emboligenous cardiopathy on the transesophageal echocardiogram. A computed tomography scan of the chest abdomen and pelvis was performed, with evidence of nodular thickening of both adrenal glands. An adrenal gland biopsy was undertaken, and the histological exam confirm the diagnosis of intravascular large B-cell lymphoma. Patient's condition rapidly worsened, evolving to depression of consciousness, cortical blindness, tetraparesis with brachial diplegia, and the patient died. CONCLUSION: The clinically heterogeneous spectrum of presentation and the lack of pathognomonic features or markers have made ante mortem clinical diagnosis of intravascular large B-cell lymphoma difficult and challenging. This report highlights the diagnostic challenge, the aggressive behavior and the devastating clinical course associated with this clinical entity.
Abstract 4293: Histamine dihydrochloride as an immune modulator for solid tumors
Authors: Kheng Newick, Shaun O'Brien, Veena Kapoor, Liang-chuan Wang, Edmund Moon, Daniel Sterman, Steven Albelda
Journal: Cancer Research (2015)

Abstract Our recent adoptive T cell transfer trial for mesothelioma revealed a striking anti-tumor response in a patient which was accompanied by anaphylaxis, suggesting endogenous histamine release. In animal models, histamine has direct and immune-based anti-tumor effects. In fact, histamine dihydrochloride is approved in Europe in combination with interleukin-2 (IL2) for leukemia treatment. We thus explored the anti-tumor role of histamine in mesothelioma and lung cancer. An in vitro MTT assay was used to measure cell proliferation. Daily doses of histamine (1 mg/kg) - alone, or in combination with other immunotherapies - was used to treat four subcutaneous flank tumor models in three different mouse strains. Flow cytometric analyses were subsequently performed on tumors. Histamine had in vitro anti-tumor activity against all five cell lines tested with an IC50 of 0.1 mg/ml. Histamine also significantly reduced tumor volume in all four in vivo models without toxic side effects. Immunodepletion studies revealed that the effect was partially due to T cells. When combined with two immunotherapy approaches (adenovirally-delivered interferon-α or a tumor antigen), anti-tumor efficacy was augmented. Histamine resulted in more interferon-γ and IL2 production by tumor-infiltrating lymphocytes, downregulation of CD206 expression on tumor-infiltrating macrophages, and reduced numbers of T regulatory cells (Tregs). This pre-clinical data suggests that histamine alone, or in combination with immunotherapy, should be explored in the treatment of mesothelioma, lung cancer, and perhaps other cancers. Citation Format: Kheng Newick, Shaun O'Brien, Veena Kapoor, Liang-chuan Wang, Edmund Moon, Daniel Sterman, Steven Albelda. Histamine dihydrochloride as an immune modulator for solid tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4293. doi:10.1158/1538-7445.AM2015-4293
Reversible Acute Muscular Syndrome in Chronic Alcoholism
Authors: Gerald T. Perkoff, Patrick Hardy, Enrique Velez-Garcia
Journal: New England Journal of Medicine (1966)

IN recent years the relation of the chronic ingestion of large amounts of alcoholic beverages to myocardial disease1 2 3 4 and to hypoglycemia5 6 7 8 has been well established. That clinical abnormalities of skeletal muscle may occur in alcoholic patients is less well known. European workers9 10 11 12 have described an acute muscular syndrome characterized by muscle aching, tenderness and edema in which hyperpotassemia, increased serum glutamic oxalacetic transaminase activity, myoglobinuria and renal damage are frequent but inconstant findings. However, only a few such patients have been recognized in this country.13 , 14 In the course of studies of muscle wasting in patients with hepatic cirrhosis, we encountered . . .
AB1077 The spread of tophaceous disease strongly predicts time to new flare in gouty arthritis
Authors: N. Schlesinger, P. Sunkureddi, R. Alten, T. Bardin, A. Shpilsky, T. Kiechle, A. So
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In gouty arthritis (GA) elevated serum urate (SU) levels lead to the monosodium urate (MSU) crystal deposition (tophi) in cartilage, tendon sheaths, and subcutaneous tissue. This usually appears late in the disease course and indicates disease severity. However, currently there is no quantitative measure to differentiate severe from less severe GA patients using spread of tophaceous disease. <h3>Objectives</h3> To develop a quantitative measure of GA severity by the number of tophi locations. <h3>Methods</h3> Pooled analysis of two 12-week studies (β-RELIEVED, N=230; β-RELIEVED II, N=226) followed by 12-week extensions, demonstrated a significant reduction in time to new flare in patients treated with canakinumab 150 mg s.c. vs. triamcinolone acetonide (TA) 40 mg i.m. (p&lt;0.0001). Additional retrospective analysis was conducted to explore the impact of the spread of tophaceous disease on time to new flare. A new quantitative measure was derived by summation of tophi locations (right upper limb, left upper limb, right lower limb, left lower limb, and one "other") resulting in a 6-point ordinal measurement scale. Number of tophi locations, using this scale, ranged from 0 to 5. The number of tophi locations was evaluated as a covariate in the Cox regression model using Wald Chi-Square test. <h3>Results</h3> The number of tophi locations revealed a high statistical significance along with treatment effect (p&lt;0.0001 for both) i.e. the fewer the number of tophi locations, the longer the time to new flare. A similar result was obtained from Kaplan-Meier (K-M) analysis using log-rank test across the strata of 3 subgroups of tophi category (0, 1-2, 3-5) [Figure]. <h3>Conclusions</h3> Our results suggest that the number of locations to which tophaceous formations have spread throughout the body leading to systemic disease is an indicator of disease severity in GA. This quantitative measure is a strong predictor of delay of new flare (the higher the number of locations the less delay in reflares). <h3>Disclosure of Interest</h3> N. Schlesinger Grant/Research support from: Novartis, Consultant for: Novartis,URL Pharma, Savient, Takeda, Rx Ensyme, Speakers Bureau: Novartis, P. Sunkureddi Consultant for: Novartis, Bristol Myers Squibb, UCB, Pfizer, Speakers Bureau: Novartis, Bristol Myers Squibb, UCB, Pfizer, R. Alten Grant/Research support from: Novartis, Consultant for: Novartis, Speakers Bureau: Novartis, T. Bardin Grant/Research support from: Menarini, Consultant for: Novartis, Ipsen, Menarini, Ardea, Biocryst, Speakers Bureau: Novartis, A. Shpilsky Shareholder of: Novartis, Employee of: Novartis, T. Kiechle Shareholder of: Novartis, Employee of: Novartis, A. So Grant/Research support from: Novartis, Consultant for: Novartis, Ardea, Speakers Bureau: Novartis, Ardea, Menarini
P889 NEW NUCLEOS(T)IDE ANALOGUE MONOPROPHYLAXIS AFTER HEPATITIS B IMMUNOGLOBULIN WITHDRAWAL IS SAFE AND EFFECTIVE AGAINST HEPATITIS B RECURRENCE AFTER LIVER TRANSPLANTATION
Authors: E. Cholongitas, J. Goulis, N. Antoniadis, I. Fouzas, G. Imvrios, T. Vasiliadis, V. Papanikolaou, E. Akriviadis
Journal: Journal of Hepatology (2014)