tbuckley/cabot-search huggingface dataset:
Abstract 731: <i>In vivo</i> fluorescence labeling of gastrointestinal stromal tumor (GIST) .
Authors: Cristina A. Metildi, Chih-Min Tang, Sharmeela Kaushal, Stephanie Y. Leonard, Paolo Magistri, Robert M. Hoffman, Michael Bouvet, Jason K. Sicklick
Journal: Cancer Research (2013)

Abstract Gastrointestinal stromal tumor (GIST), the most common sarcoma, metastasizes hematogenously and peritoneally. Tumor-free margins and complete cytoreduction of metastatic disease are critical for decreasing recurrence. Since most GISTs overexpress KIT (c-KIT, CD117), we hypothesized that fluorescently labeled anti-KIT antibodies can improve detection of GIST. KIT K641E+/− transgenic mice that spontaneously develop cecal GIST, and wild-type C57BL/6 mice were used in this study. Wistar rat anti-mouse monoclonal c-KIT antibody was labeled with the AlexaFluor 488. The conjugated anti-KIT-Alexa 488 antibody (50-100 μg) was delivered via tail vein at 24 hours prior to standard staging laparoscopy. A pediatric laparoscopic grasper was inserted in the left lower quadrant for bowel mobilization in order to visualize the cecum. All 4 quadrants of the peritoneal cavity were examined systematically under both fluorescence and bright light. Post laparoscopy, mice were sacrificed and their abdomens exposed for Olympus OV-100 imaging. All tumors were resected and confirmed by H&amp;E. We divided the mice into 4 groups. KIT K641E+/− mice received anti-KIT antibody (N=4) or control antibody (N=3). Wild-type mice received the same antibodies (N=3 per group). Fluorescence laparoscopy demonstrated a high tumor signal-to-background noise ratio. Upon whole body imaging used to detect gross tumors, there were 2 false positive and 0 false negative results, leading to an accuracy of 92%. The sensitivity, specificity, positive and negative predictive values were: 100%, 87%, 85%, and 100%, respectively. This method has several translatable applications: 1) identification of peritoneal metastases; 2) following disease response; 3) non-radioactive imaging; 4) endoscopic differentiation of gastric GISTs from leiomyomas or schwannomas; 5) laparoscopic staging; and 6) assessment of margin status. Citation Format: Cristina A. Metildi, Chih-Min Tang, Sharmeela Kaushal, Stephanie Y. Leonard, Paolo Magistri, Robert M. Hoffman, Michael Bouvet, Jason K. Sicklick. In vivo fluorescence labeling of gastrointestinal stromal tumor (GIST) . [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 731. doi:10.1158/1538-7445.AM2013-731
THU0197 Presence of Antibodies to Adalimumab and Infliximab in Patients with Rheumatoid Arthritis in Clinical Remission
Authors: G. Eng, V. Fana, E. Omerovic, P. Højsgaard, H. M. Lindegaard, E. K. Jensen, P. N. Bouchelouche
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Increasing use of TNF-α inhibitors (TNFi) has revealed that some patients develop antibodies towards TNFi (anti-TNFi) and that some of these antibodies neutralize the effect of the TNFi and thereby impair efficacy of the medication. A relationship has been established between high levels of anti-TNFi and/or low levels of TNFi and impaired clinical response<sup>1-3</sup>. Knowledge regarding anti-TNFi may aid in determining which patients will not benefit from continued TNFi treatment. <h3>Objectives</h3> To investigate the presence of neutralizing anti-TNFi towards adalimumab and infliximab and the serum-concentration of the prescribed TNFi, in patients with rheumatoid arthritis (RA) in clinical remission. <h3>Methods</h3> Patients with RA from six out-patient clinics in Denmark, treated with adalimumab or infliximab, and in clinical remission (DAS28CRP&lt;2.6) were included and concentrations of anti-TNFi and TNFi were determined. <h3>Results</h3> Among the 93 patients included, 13 tested positive for anti-TNFi. Of these, 4% (2/49) treated with adalimumab and 25% (11/44) treated with infliximab tested positive for anti-TNFi. Median concentrations of TNFi were 9.68 microg/mL (&lt;0.65 – 30.71) for adalimumab and a median of 3.93 microg/mL (0.67 – &gt;31) for infliximab. <h3>Conclusions</h3> In the present study, 14% of patients in remission had developed anti-TNFi whilst undergoing treatment with adalimumab or infliximab. Future research may reveal, if presence of anti-TNFi and concentration of TNFi is a predictor of continued remission in case of termination of TNFi treatment. <h3>References</h3> Bendtzen K, Geborek P, Svenson M, Larsson L, Kapetanovic M C, Saxne T. Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab. Arthritis Rheum 2006;54:3782-3789. Radstake T R, Svenson M, Eijsbouts A M, van den Hoogen F H, Enevold C, van Riel P L et al. Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis. Ann Rheum Dis 2009;68:1739-1745. Bartelds G M, Krieckaert C L, Nurmohamed M T, van Schouwenburg P A, Lems W F, Twisk J W et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA 2011;305:1460-1468. <h3>Acknowledgements</h3> We would like to thank the Danish Rheumatism Association, the Oak Foundation and Region Zealand for grant support. We are grateful to Klaus Bendtzen, Michael Stoltenberg and Marcin Szkudlarek for their insight and advise. <h3>Disclosure of Interest</h3> None Declared
THE RELATIONSHIP BETWEEN TOOTH LOSS, CARDIOVASCULAR BIOMARKERS AND OUTCOMES IN PATIENTS WITH STABLE CORONARY HEART DISEASE
Authors: Ola Vedin, Emil Hagstrom, Ollie Ostlund, Alvaro Avezum, Andrzej Budaj, Marcus Flather, Robert Harrington, Wolfgang Koenig, Joseph Soffer, Agneta Siegbahn, Philippe Steg, Ralph Stewart, Lars Wallentin, Harvey White, Claes Held
Journal: Journal of the American College of Cardiology (2016)
Case 11-2014
Authors: Matthias Eikermann, George Velmahos, Suhny Abbara, Paul L. Huang, Shawn P. Fagan, Ronald E. Hirschberg, John Y. Kwon, Vania Nosé
Journal: New England Journal of Medicine (2014)

Any reader of the Journal who uses the Case Records of the Massachusetts General Hospital as a teaching exercise or reference material is now eligible to receive a complete set of PowerPoint slides, including digital images, with identifying legends, shown at the live Clinicopathological Conference (CPC) that is the basis of the Case Record.This slide set contains all of the images from the CPC, not only those published in the Journal.Radiographic, neurologic, and cardiac studies, gross specimens, and photomicrographs, as well as unpublished text slides, tables, and diagrams, are included.Every year 40 sets are produced, averaging 50-60 slides per set.Each set is supplied on a compact disc and is mailed to coincide with the publication of the Case Record.
AB0696 Predictors of poor response to 6-months methotrexate therapy in a juvenile idiopathic arthritis cohort of patients
Authors: R. Marques, F. Ramos, I. Perpétuo, S. Fernandes, A. C. Furtado, A. F. Mourão, F. Martins, J. E. Fonseca, J. A. Pereira da Silva
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The identification of predictive factors of poor response to methotrexate (MTX) in juvenile idiopathic arthritis (JIA) patients could contribute to optimize the treatment strategy, namely by the earlier introduction of biological treatments. <h3>Objectives</h3> To identify baseline clinical or laboratorial predictive factors of MTX poor response at 6 months in patients with JIA. <h3>Methods</h3> In a cohort of 141 JIA patients registered in Reuma.pt (the Portuguese Register of Rheumatic Diseases)we selected patients diagnosed after 2000 and that were treated at least for 6 months with MTX (at least 10mg/m<sup>2</sup>). Bivariate and multivariate logistic analyses were used to identify the predictors for non-response to MTX treatment during the first 6 months of treatment. Non-response to MTX was defined according the American College of Rheumatology pediatric 70 criteria. Concomitant treatment with NSAIDs and corticosteroids up to 10mg was allowed for all treatment groups. For this analysis we included: sex, age, age at disease onset, subtype, disease duration, rheumatoid factor (RF), ANA, HLA-B27, uveitis, age at MTX onset, disease duration until the start of MTX, baseline physician and patient/parents VAS, baseline active and limited joints and ESR. <h3>Results</h3> From the 58 patients identified, 23 were excluded (2 started biological therapy before 6 months, 3 were on concomitant DMARD's, 12 had insufficient data, 1 developed criteria for systemic lupus erythematosus, 3 had interrupted MTX and 2 were loss for follow-up). From our population 43% have achieved ACR-ped 70 response and the remaining 57% did not reach this response criterion. We found no differences in the parameters analyzed between the 2 groups, except the age of MTX onset (p=0.03; responders 5 [3-11.5], non-responders 17.5 [11-22.6]) and parents/patients VAS (p=0.047; responders 50 [40.9-61.6], non-responders 20 [13-53.6]). We observed that older age at the beginning of MTX and lower patient/parents VAS were independently associated with poor response to MTX therapy. Accordingly, we have introduced in a logistic regression model both of these parameters. After multivariate analysis, age at the beginning of MTX was the only determinant independently associated with ACR-ped 70 non responders (p=0.05; OR 0.83). <h3>Conclusions</h3> In our cohort of JIA patients, older age at MTX onset was correlated with poorer response to a 6-month MTX course. <h3>Disclosure of Interest</h3> None Declared
Relationship between Bronchial Responsiveness and Clinical Evolution in Infants Who Wheeze
Authors: CHRISTOPHE DELACOURT, MARIE-ROSE BENOIST, SERGE WAERNESSYCKLE, PATRICK RUFIN, JEAN-JACQUES BROUARD, JACQUES DE BLIC, PIERRE SCHEINMANN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Recurrent illness involving wheezing during the first years of life is transient in most children. The role of bronchial hyperresponsiveness as a factor influencing the persistence of wheezing from infancy to school age remains unknown. In a prospective study we investigated whether infants who wheezed and subsequently developed persistent asthma differed from infants who wheezed and later became asymptomatic either in the initial degree of bronchial hyperresponsiveness or in the persistence of bronchial hyperresponsiveness with age. One hundred and twenty-nine infants with three or more wheezing episodes before 2 yr of age were followed during 4 yr with a clinical evaluation and a methacholine challenge performed every 6 mo until the child was 4 yr old and once per year thereafter. The clinical score significantly improved with time in most children. The proportion of children with persistent wheezing after 2 and 4 yr of follow-up was only 31% and 20%, respectively. Persistent wheezers had significantly lower VmaxFRC values at initial evaluation and higher SRaw values at the end of follow-up than infants who became asymptomatic. We used transcutaneous oxygen tension (PtcO(2)) to measure the response to methacholine. No significant difference in PD(15) PtcO(2) between groups with subsequently different clinical progression was observed at initial evaluation. Bronchial hyperresponsiveness persisted 4 yr later in all children but children with persistent wheezing showed significantly lower PD(15) PtcO(2) values than children who became asymptomatic, as early as 30 mo of age. However, an acceptable early PD(15) PtcO(2) cut-off point predictive for subsequent clinical progression could not be identified. The level of bronchial hyperresponsiveness in infants who wheezed was not predictive of the persistence of asthma 4 yr later.
Leukodystrophy and Gene Therapy with a Dimmer Switch
Authors: Paul J. Orchard, John E. Wagner
Journal: New England Journal of Medicine (2011)

Globoid-cell leukodystrophy is a neurodegenerative disease characterized by the loss of central and peripheral myelin. It is treated by autologous transplantation of hematopoietic stem cells. A recent study provides proof of concept of a new approach to gene therapy.
Abstract 2070: Mir-199a is downregulated in hypoxia and targets HIF1α in ovarian cancer cells
Authors: Hemant Joshi, Indira Subramanian, Goutam Ghosh, Yan Zeng, Min Zhao, Sundaram Ramakrishnan
Journal: Cancer Research (2010)

Abstract HIF1 is the main transcriptional regulator of the hypoxic response in mammalian cells and plays an important role in the adaptation of tumor cells to hypoxic microenvironments. While normally degraded under normoxic conditions via oxygen-dependent, ubiquitin-based mechanisms, HIF1α protein, which, with the constitutively expressed HIF1β forms the HIF1 heterodimer, is stabilized in hypoxic tumor cells. Stabilization of HIF1α protein under hypoxia leads to transactivation of a variety of angiogenic and tumorigenic genes including VEGF and matrix metalloproteinase 2. Clinically, high levels of HIF1 in tumors translate to increased patient morbidity and mortality. Our studies show that HIF1α, in addition to being regulated at the protein level, is also directly regulated by microRNAs, small 20-22 base ribonucleotides that specifically bind to the 3’ untranslated regions (UTRs) of target mRNA to inhibit translation or induce degradation. Based on bioinformatics and microRNA-target databases, we determined that HIF1α contains a potential binding site in its 3’ UTR for mir-199a, which, based on our microarray and RT-qPCR data, is significantly downregulated in hypoxic ovarian cancer cells compared to normoxia. Using a luciferase reporter construct in which luciferase expression is under control of the HIF1α 3’ UTR, we showed that overexpression of mir-199a in A2780 or MA148 cells leads to suppression of the luciferase signal. Mutation of the mir-199a binding site in the HIF1α 3’ UTR resulted in no change in luciferase signal with mir-199a overexpression, indicating that mir-199a directly targets the HIF1α 3’ UTR. Furthermore, decreasing mir-199a levels, either by incubating cells in hypoxia or using a morpholino specifically targeting mir-199a, leads to increased levels of HIF1α protein as determined by western blot and increased transcripts of HIF1-activated genes such as VEGF as measured by RT-qPCR. Conversely, overexpression of mir-199a leads to decreased HIF1α protein and VEGF transcript levels. Together, our findings have significant implications in the study of HIF1α regulation in cancers. Mir-199a may have a role in future therapeutic strategies to modulate the tumor microenvironment to limit hypoxia-driven tumor progression and metastasis. 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 2070.
Abstract 3304: EAPII/TTRAP is overexpressed in HNSCC
Authors: Chunyang Li, Songqing Fan, Shi-yong Sun, Fadlo R. Khuri, Runzhao Li
Journal: Cancer Research (2010)

Abstract EAPII/TTRAP, a novel protein we previously identified, was most recently recognized as the first enzyme that removes topoisomerase-mediated adducts at the 5′-phosphotyrosyl bond. EAPII/TTRAP restores 5′phosphate termini at double strand breaks preparing them for ligation. However, the physiological and pathological roles of EAPI I/TTRAP in human cells are elusive; in particular, it is unknown whether EAPII/TTRAP is involved in cancer. To determine the EAPII expression profile in the development of the Head and Neck Squamous Cell Carcinoma (HNSCC), we have developed a monoclonal antibody against EAPII suitable for immunohistochemistry (IHC). IHC was carried out in an HNSCC tissue array containing 34 cases of HNSCC and 12 peri-cancer or normal tissues. EAPII is not detectable in normal human oral squamous cells where HNSCC arises. With increased cell proliferation, weak staining of EAPII in the nucleus occurs. However, EAPII expression is significantly observed in HNSCC: Compared to 8% (1/12) in peri-cancer tissue, 82% (28/34) of HNSCC showed strong cytoplasmic-positive staining while nuclear staining reduced from 75% (9/12) to 35% (12/34). This result indicates that EAPII translocation to the cytoplasm might be an oncogenic factor that contributes to the progression of HNSCC. Consistent with the IHC study, high levels of EAPII expression are observed in many HNSCC cancer cell lines. Furthermore, lentivirus-delivered EAPII small hairpin RNA (shRNA) was employed to knockdown EAPII expression in HSNCC 686Ln-M4E cells. Cell growth curves were analyzed by SRB method. Lower cell growth was observed in the cells with reduced EAPII protein levels compared with cells infected with vector control or scramble shRNA. Altogether, our data support the hypothesis that EAPII is a potential oncogenic factor and that the elevated level of EAPII may be involved in the HNSCC development. The identification of the role of EAPII in the HNSCC development using animal models will provide further insight into the biological significance of EAPII in cancer development and progression. This work was supported in part by National Cancer Institute award 5 P50 CA128613 SPORE in Head and Neck Cancer (SYS) and Startup Fund from the Department of Hematology and Medical Oncology (RL). 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 3304.
Abstract 4865: Pak1 links the Wnt/β-catenin pathway to ErbB2 signaling in breast cancer cells
Authors: Luis E. Arias Romero, Olga Villamar Cruz, Jonathan Chernoff
Journal: Cancer Research (2012)

Abstract Several studies suggest that Pak1 plays an important role in the genesis of breast cancer, but despite the similarity in their sequences, the contribution of the closely related enzyme Pak2 to this disease remains unclear. To establish the function of Paks in ErbB2 driven transformation, we used a three-dimensional tissue culture system of human mammary epithelial cells that stably co-express a chemically-activatable form of ErbB2 and doxycycline (DOX) inducible shRNAs against Pak1 or Pak2. We observed that silencing of Pak1 but not of Pak2 has a dramatic effect in cell proliferation and apoptosis. As expected, activation of ErbB2 induced growth factor-independent proliferation and disruption of 3D acinar-like structures via ERK and Akt signaling. In contrast, silencing of Pak1 compromised activation of ERK, resulting in reversion of the malignant phenotype and restoration of normal acinar architecture. Surprisingly, silencing of Pak2 also compromised ERK activation, but cannot restore normal morphology. Further, we found that ErbB2-amplified breast cancer cells expressing a DOX inducible shRNA against Pak1 formed significantly smaller tumors than cells expressing either GFP or a DOX inducible shRNA against Pak2 in SCID mice as the result of the inhibition of ERK. A phosphoproteomic analysis showed that several signaling pathways, e.g. Wnt and Mdm2-p53, are down regulated in our Pak1 deficient cell line. We found that the shPak1 cell line, but not the shPak2 deficient cell line has a dramatic reduction in total β-catenin levels, and that blocking β-catenin with chemical inhibitors restored normal acinar architecture. Finally, we found that targeting Pak and/or β-catenin in combination with trastuzumab sensitized trastuzumab-resistant breast cancer cells to trastuzumab, suggesting the potential clinical application of this strategy to overcome trastuzumab resistance. 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 4865. doi:1538-7445.AM2012-4865
TCTAP A-108 Determination of the Behavior of Coronary Physiology Under Resting Conditions: The Implications for Stenosis Assessment
Authors: Sukhjinder Nijjer, Guus De Waard, Tim Van De Hoef, Sayan Sen, Ricardo Petraco, Mauro Echavarria-Pinto, Martijn Van Lavieren, Paul Knaapen, Ibrahim Danad, Niels Van Royen, Javier Escaned, Justin E. Davies
Journal: Journal of the American College of Cardiology (2015)
Authors' reply to Nestle
Authors: H. Barennes, L. M Srour
Journal: BMJ (2009)

Stieger’s letter shows misunderstanding of the international code on the marketing of breast milk substitutes by Nestle (Thai).1 2 The coffee creamer is only the tip of the iceberg.

The obvious and ongoing code violations include marketing of formula and non-formula products with the logo of a baby bear held in the breastfeeding position (article 5). Sweetened condensed milk (45% sugar, 20% skimmed milk powder and palm oil) with the Bear Brand logo was still on sale in Vientiane in September 2008. In neighbouring Thailand, an aggressive advertising campaign began in 2007 with the Bear Brand logo on sweetened condensed milk, milk …
Multiple esophagopleural and esophagobronchial fistulas in a patient with Crohn's disease
Authors: A. Albuquerque, R. Ramalho, G. Macedo
Journal: Endoscopy (2012)

A 56-year-old man was admitted because of severe weight loss, anorexia, and dyspnea over a 2-month period. He had been diagnosed in 1985 with Crohn's colitis and in 2001 he was admitted and underwent a total colectomy with formation of an ileostomy because of a severe disease flare. Subsequently, he had missed several follow-up outpatient consultations and was not taking any medication.