tbuckley/cabot-search huggingface dataset:
Abstract 949: Disruption of growth hormone signaling improves the efficacy of conventional chemotherapy in a rat model of mammary cancer
Authors: Daniel D. Lantvit, Qi Shen, Jilai Yang, Terry G. Unterman, Steven M. Swanson
Journal: Cancer Research (2012)

Abstract Epidemiological and laboratory based studies suggest that the growth hormone/insulin-like growth factor I (GH/IGF-I) axis is positively correlated with a variety of different cancer types. In recent years, our research team has developed animal models to explore the role of GH signaling in carcinogenesis. These include rat and mouse models of mammary, prostate and colon cancer in which the GH receptor is knocked out, antagonized or GH itself is knocked out. In all of these models, we observed a significant (50% or more) disruption in carcinogenesis when GH signaling is impaired compared to normal controls. Our initial studies demonstrated that carcinogenesis can be effectively inhibited by the disruption of GH signaling in animals lacking genes for wild-type GH or the GH receptor. These findings are consistent with a recent report by Guevara-Aguirre and colleagues (Sci Transl Med 3: 70ra13, 2011) who found that a population lacking a functional GH receptor (Laron syndrome) were cancer free except for one patient whose ovarian cancer did not recur after chemotherapy. A control cohort of relatives suffered a 20% mortality rate from cancer. The response of the Laron patient's tumor to chemotherapy inspired us to hypothesize that the lack of GH signaling may render a tumor more vulnerable to conventional chemotherapy. To test this hypothesis, we treated 6 Spontaneous Dwarf rats (SDR) with GH (150 μg/kg twice daily) beginning at 3 weeks of age; 6 control rats received vehicle injections. At 4 weeks of age, all rats were exposed to a single injection of the mammary carcinogen N-methyl-N-nitrosourea (50 mg/kg). Once a rat developed a mammary tumor of 1cm in diameter, GH or vehicle injections were halted and doxorubicin (1.25 mg/kg; 6 injections over 2 weeks) treatments began. The dose of doxorubicin that was chosen was lower than that normally used to induce regression in this model. We observed that tumor growth in wild-type rats was stopped and remained static during treatment with doxorubicin. In contrast, the tumors of SDR rats, lacking GH, all regressed in response to doxorubicin treatment (p &amp;lt; 0.005). These data suggest that disrupting GH signaling may enhance the efficacy of conventional anticancer chemotherapy. Pegvisomant, a GH antagonist approved by the FDA for the treatment of acromegaly, or one of several investigational drugs currently under study for the disruption of IGF-I signaling, may serve to translate the findings presented here to the clinic to improve current cancer therapy regimens. This work was supported by NIH grant R01-CA099904. 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 949. doi:1538-7445.AM2012-949
Abstract LB-176: A novel high density DNA methylation array with single CpG site resolution
Authors: Marina Bibikova, Bret Barnes, Chan Tsan, Vincent Ho, Brandy Klotzle, Jennie M. Le, David Delano, Kevin L. Gunderson, Jian-Bing Fan, Richard Shen
Journal: Cancer Research (2011)

Abstract Aberrations in DNA methylation patterns are widely recognized as a hallmark of the cancer cell. DNA methylation has emerged as a promising biomarker for the detection and classification of various types of cancer, and ability to accurately assess the DNA methylation changes plays an important role in understanding of disease onset and progression. We developed a new generation of genome-wide DNA methylation BeadChip which allows high-throughput methylation profiling of human genome. The new high density BeadChip can assay over 480K CpG sites and analyze twelve samples in parallel. The innovative content includes coverage of 99% of RefSeq genes with multiple probes per gene, 96% of CpG islands from the UCSC database, CpG island shores and additional content selected from whole-genome bisulfite sequencing data and input from DNA methylation experts. The well-characterized Infinium® assay is used for analysis of CpG methylation using bisulfite-converted genomic DNA. In this assay, unmethylated cytosines (C) are converted to uracil (U) when treated with bisulfite, while methylated cytosines remain unchanged. The assay design is using single probe assays for CpG loci with up to two underlying CpG dinucleotides, and two-probe assays for CpG loci with multiple underlying CpG sites, with one probe querying the “unmethylated” allele and the other probe querying the “methylated” allele. The assays are designed under the assumption that methylation is regionally correlated (within 50 base pairs) and that all CpG sites underlying the probe are assumed to be “in phase” with the queried CpG site. For the BeadChip development, we used methylation standards created by de-methylating gDNA with Phi29 whole genome amplification, methylating the amplified DNA with SssI methylase and mixing the unmethylated and methylated DNA in a 1:1 ratio to create a 50% methylation state. 500 ng gDNA input is used for bisulfite conversion and is sufficient for two assays. Reproducible DNA methylation profiles were obtained between replicates (an average R2 of 0.98). We applied this technology to DNA methylation analyses in cancer cell lines of different tissue of origin and normal DNA samples derived from multiple tissues. Highly specific methylation signatures were obtained for each sample type. The ability to determine genome-wide methylation patterns will rapidly advance methylation research and ultimately lead to the development of powerful tools for diagnosis, prognosis, and treatment of human diseases. 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 LB-176. doi:10.1158/1538-7445.AM2011-LB-176
Case 10-2004
Authors: Jay A. Fishman, Bimalangshu R. Dey, Robert P. Hasserjian
Journal: New England Journal of Medicine (2004)

Presentation of Case Dr. Bimalangshu R. Dey: A 58-year-old man with a large sacral ulcer was admitted to the hospital for chemotherapy to treat acute myeloid leukemia.The patient had had recurrent infections of a pilonidal cyst for 20 years; the infections had required surgical débridement on multiple occasions. Six weeks before admission to this hospital, he was admitted to another hospital with a temperature as high as 39.4°C with chills and rigors. The pilonidal cyst had a malodorous, purulent discharge and was surrounded by fluctuant, swollen tissue. Surgical incision and drainage were performed. The white-cell count was 7500 per . . .
Abstract 5477: Ambient exposure to air pollutants and risk of neuroblastoma
Authors: Julia E. Heck, Michelle Wilhelm, Christina Lombardi, Myles Cockburn, Beate Ritz
Journal: Cancer Research (2012)

Abstract Background: Some reports have linked neuroblastoma to parental occupational exposure to hydrocarbons and other chemicals. Our aim was to assess the association between neuroblastoma and exposure in pregnancy and early life to criteria air pollutants (CO, O3, PM10, PM2.5, and NOx) and to certain air toxics which are established or suspected carcinogens (benzene, 1,3 butadiene, PAHs, xylenes, carbon tetrachloride, and others). Of the criteria air pollutants, CO and NOx arise primarily from motor vehicle exhaust and thus best represent traffic-related pollution, while O3 and PM arise from a variety of sources and should be considered as markers of regionally distributed background air pollution. Methods: The Air Pollution and Childhood Cancers study ascertained all cancers diagnosed 1988-2007 in the California Cancer Registry among children less than 6 years of age; we were able to match 89% to a California birth certificate. Controls were frequency-matched by year of birth and selected at random from California birthrolls. The final analysis included 1073 neuroblastoma cases and 209,700 controls. Home addresses, as listed on birth certificates, were geocoded and linked to the nearest California Air Resources Board air pollution monitor. For those living within 5 miles of an air pollution monitor, average measurements of criteria air pollutants and air toxics were determined for each trimester of pregnancy and for the first year of life. Multivariate regression models were used to assess the relation between air pollutants and neuroblastoma, with adjustment for maternal race, socioeconomic status, and birth year. Odds ratios compare children in the highest quartile of exposure to those in the lowest exposure group. Results: Exposure to ozone in the 1st (OR =1.27, 95% CI 1.01, 1.60) and 2nd (OR=1.30, 95% CI 1.02, 1.64) trimesters was associated with an increased risk of neuroblastoma (n cases=565 within 5 miles of a monitor). Neuroblastoma was also associated with exposure to carbon tetrachloride in the first trimester (OR=2.62, 95% CI 1.06, 6.46), although this result was based upon 60 cases living within 5 miles of an air toxics monitor. We found no evidence of associations between neuroblastoma and other criteria air pollutants nor other air toxics, including no evidence of associations with traffic-related pollution. Conclusions: This is the first study to suggest a relation between neuroblastoma and ambient levels of air pollution. 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 5477. doi:1538-7445.AM2012-5477
Abstract 5294: Increased angiogenesis resulting from TIMP-1 inhibition of TSP-1 is mediated by PI3kinase and FAK interactions
Authors: Juhi Ohja, Sitaram Gayatri, Srilatha Nalluri, Amyn M. Rojiani, Mumtaz V. Rojiani
Journal: Cancer Research (2012)

Abstract Tissue Inhibitor of Matrix Metalloprotease -1 (TIMP-1), one of the four natural inhibitors of matrix metalloproteinases was initially identified for its Erythroid Potentiating Activity. Since then, it has been shown to independently induce cell proliferation and inhibit apoptosis in a number of cell types. TIMP-1 has also been shown to promote, but also more often to inhibit angiogenesis. Previously, we have shown that TIMP-1 overexpression in a lung adenocarcinoma cell line (H2009) resulted in more aggressive and vascular tumors in nude mice and increased capillary network formation and tumorigenicity in vitro. An angiogenesis pathway-specific gene array had identified a 3-fold reduction in thrombospondin 1 (TSP-1) levels in the TIMP-1 overexpressing clone HB-1. TSP-1 siRNA clone exhibited a similar increase in in vitro angiogenesis assays. In the present study, we have sought to identify the signaling pathway involved whereby TIMP-1 inhibits TSP-1. To this end, we have used specific inhibitors to inhibit TIMP1 initiated signaling pathways. MAP kinase, PI3/Akt inhibitors were used, either singly or in combination with Focal Adhesion kinase (FAK) inhibitor. Our results indicate a synergistic interaction between PI3/Akt pathway and FAK signaling, which restores TSP-1 levels by approximately 3-fold relative to control. Gelatin zymography of serum-free conditioned media (SFCM) revealed a reduction in proMMP-9 level in the HB-1 clone versus H2009. Additionally MMP9 specific ELISA reveals a two-fold reduction in MMP9 levels. This is in tune with the role of TSP-1 as an inhibitor of MMP-9 activation such that decreased TSP-1 level results in increased activation of MMP-9 with a concomitant reduction in the extracellular level of proMMP-9. Thus our findings define interaction of TIMP-1 via PI3kinase and FAK signaling. resulting in TSP-1 decrease and subsequent downstream promotion of angiogenesis with increased tumor kinetics. 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 5294. doi:1538-7445.AM2012-5294
Acute Renal Failure Caused by Phenylbutazone
Authors: Joseph H. Richardson, Henry H. Alderfer
Journal: New England Journal of Medicine (1963)

PHENYLBUTAZONE, a congener of aminopyrine, can damage many organs. Injury to the skin,1 , 2 lungs,3 , 4 heart,3 , 4 liver,4 5 6 7 kidneys,3 , 4 , 8 , 9 bone marrow,1 adrenal glands3 and intestine3 has been reported. A single organ may be involved, or multiple organs may be affected simultaneously.5 The histologic changes in the damaged organs have not been uniform. In 1 case the heart was involved by focal necrosis of myocardial fibers,4 and in another arteritis affected the myocardium.3 Acute renal failure caused by phenylbutazone is rare. We are reporting the case presented below to correlate the histopathologic changes with those in other cases studied with renal biopsies. This . . .
ESTUDIO DEL MANEJO ENDOSCÓPICO DE LOS CUERPOS EXTRAÑOS DIGESTIVOS
Authors: C Jimeno Ayllón, R Martínez Fernández, CJ Gómez Ruiz, J García-Cano Lizcano, J Morillas Ariño, L Serrano Sánchez, AK Reyes Guevara, T Martínez Pérez, JI Pérez García, A Pérez Sola
Journal: Endoscopy (2011)

Introducción: La ingestión de cuerpos extraños y la impactación de bolos alimentarios ocurre con frecuencia, aunque en un 80% de los casos avanzan espontáneamente a través del tubo digestivo sin necesidad de intervención. A pesar de su frecuencia, no es desdeñable su tasa de mortalidad, con 1500 muertes anuales en EEUU por este motivo.
OP0309-HPR Knee Joint Stabilization Therapy in Patients with Osteoarthritis of the Knee: A Randomized, Controlled Trial
Authors: J. Knoop, J. Dekker, M. van der Leeden, M. van der Esch, C. A. Thorstensson, M. Gerritsen, R. E. Voorneman, W. F. Peter, M. de Rooij, S. Romviel, W. F. Lems, L. D. Roorda, M. P. Steultjens
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Abstract</h3> Identical sensory stimuli can lead to different neural responses depending on the instantaneous brain state. Specifically, neural excitability in sensory areas may shape the brain’s response already from earliest cortical processing onwards. However, whether these dynamics affect a given sensory domain globally or occur on a spatially local level is largely unknown. We studied this in the somatosensory domain of 38 human participants with EEG, presenting stimuli to the median and tibial nerves alternatingly, and testing the co-variation of initial cortical responses in hand and foot areas, as well as their relation to pre-stimulus oscillatory states. We found that amplitude fluctuations of initial cortical responses to hand and foot stimulation – the N20 and P40 components of the somatosensory evoked potential (SEP), respectively – were not related, indicating local excitability changes in primary sensory regions. In addition, effects of pre-stimulus alpha (8-13 Hz) and beta (18-23 Hz) band amplitude on hand-related responses showed a robust somatotopic organization, thus further strengthening the notion of local excitability fluctuations. However, for foot-related responses, the spatial specificity of pre-stimulus effects was less consistent across frequency bands, with beta appearing to be more foot-specific than alpha. Connectivity analyses in source space suggested this to be due to a somatosensory alpha rhythm that is primarily driven by activity in hand regions while beta frequencies may operate in a more hand-region-independent manner. Altogether, our findings suggest spatially distinct excitability dynamics within the primary somatosensory cortex, yet with the caveat that frequency-specific processes in one sub-region may not readily generalize to other sub-regions.
Abstract P1-09-01: Long-term effect of tamoxifen use on the risk of contralateral breast cancer
Authors: L Mellemkjær, M Steding-Jessen, K Frederiksen, M Andersson, JH Olsen
Journal: Cancer Research (2012)

Abstract Background: Tamoxifen has been used widely in the treatment of breast cancer due to its beneficial effects on recurrences and mortality. Both randomized trials and observational studies give evidence that tamoxifen also reduces the incidence of contralateral breast cancer. The effect of tamoxifen seems to be present not only during treatment but also after termination of treatment, but the question is how long this effect lasts. Few studies have presented long-term follow-up data on risk of contralateral breast cancer after tamoxifen treatment. Material and Methods: In the Danish Breast Cancer Cooperative Group (DBCG) Database, we identified 50,323 women who had undergone surgery for invasive breast cancer and who had received treatment according to DBCG guidelines during 1978–2007. Among these women, 16,319 were users of tamoxifen while 34,004 were non-users. Contralateral breast cancer cases were identified in the Danish Cancer Registry and in the DBCG Database through 2009. The incidence of contralateral breast cancer among users of tamoxifen was compared to that of non-users by estimating incidence rate ratios (IRRs) in Cox regression analyses with adjustment for age at first breast cancer diagnosis, calendar period at first breast cancer diagnosis, histology of first breast cancer, radiotherapy, chemotherapy and other endocrine treatments besides tamoxifen. Results: During follow-up, 295 cases of contralateral breast cancer were observed among users of tamoxifen while 1,485 cases were observed among non-users resulting in an IRR of 0.82 (95% CI = 0.71–0.94) after adjustments. Further analyses will include calculation of IRRs for contralateral breast cancer by time since breast cancer diagnosis, duration of tamoxifen and time since cessation of tamoxifen as well as calculation of IRRs after restriction to estrogen receptor positive breast cancer patients. Results of these analyses will be presented. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-09-01.
SP0054 Immediate Access to Rheumatology - Are Quicker Answers Better Answers?
Authors: K. Machold
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Among the many patients with Rheumatic and Musculoskeletal Diseases (RMDs) who can and should be appropriately diagnosed and treated by General Practitioners or Orthopaedic Specialists, a substantial minority requires Rheumatologists and their special expertise. This expertise is frequently not readily accessible due to limited availability of Rheumatologists, limited knowledge concerning RMDs on the side of both patients and physicians, or geographic obstacles. Therefore, delays in diagnosis and treatment by far exceed the threshold considered harmless. Our approach to shorten these delays was to establish an immediate access clinic (IAC) in our large University Department. This IAC offers "low threshold" access for patients and their physicians to specialist assessment, recommendations, and care. Analysis of the outcomes of this IAC approach demonstrated that less than 45% of the patients were considered to need specialists' diagnosis/care at time of presentation. A typical assessment in the IAC usually lasts less than 10 minutes, nevertheless, follow-up after 6-12 months showed that &gt;75% of the diagnoses of inflammatory rheumatic diseases initially suspected at the IAC proved to be correct. Over 60% of patients who in the opinion of the Rheumatologist did not require specialty care stated that their problems had fully resolved at follow-up. Despite the easy access offered by this clinic, only a minority of patients (21.5%) presented with symptoms of less than three months. In conclusion, the reliability of recommendations given in the IAC appears to be high, with the main advantage of virtually complete elimination of waiting times. Our approach may serve as a model for improving access to Rheumatologic care without loss of quality. <h3>Disclosure of Interest</h3> None Declared
O7.06 * MAGNETIC NANOPARTICLES CONJUGATED TO A RECOMBINANT HEAT SHOCK PROTEIN HSP70 FOR TARGETING EXPERIMENTAL GLIOBLASTOMA
Authors: M. Shevtsov, B. Nikolaev, L. Yakovleva, Y. Marchenko, A. Dobrodumov, B. Margulis, A. Ischenko, W. Khachatryan, I. Guzhova
Journal: Neuro-Oncology (2014)

Superparamagnetic nanoparticles (SPIONs) due to their unique properties could be applied for theranostic approach in neuro-oncology. Accumulation and retention of the nanoparticles in the tumour can be directly imaged by MRI proving its application as contrast agents. Due to high heating capacity SPIONs could also be applied for thermotherapy of brain tumours. To further increase the biocompatibility and targeted delivery of SPIONs we have functionalized the surface of particles with recombinant heat shock protein Hsp70. Nuclear magnetic resonance (NMR) spectra and magnetic relaxation times of the synthesized conjugates T1, T2, T2* were measured with the help of an NMR spectrometer (CXP-300, Bruker) in a magnetic field of 7.1 T. Hsp70-SPIONs relaxivity corresponded to the properties of negative contrast agents with a hypointensive change of resonance signal in MR imaging. In series of in vitro experiments we observed enhanced internalization of the SPION-Hsp70 conjugates by C6 glioma cells in comparison to control SPIONs. The contrast-enhancing ability of SPION-Hsp70 conjugates was analyzed in the model of intracranial C6 glioma in rodents. The rat images were acquired with the help of a Bruker Avance II NMR spectrometer equipped with a microtomographic accessory at a magnetic field of 11 T. In vivo analysis of the conjugates distribution in the model of intracranial glioma revealed the retention of the functionilzed particles inside the tumour site. Negative contrast tumor enhancement in the T2-weighted MR images was higher in the case of Hsp70-SPIONs in comparison to non-modified SPIONs. Histological analysis of the brain sections confirmed the retention of the Hsp70-SPIONs in the glioma tumor but not in the adjacent normal brain tissues. Immunofluoresence studies confirmed that retention in the glioma of nanoparticles was due to the receptor-mediated endocytosis of the SPION-Hsp70 conjugates via the CD40 receptors. The uptake of SPION-Hsp70 by tumour cells permitted MRI contrast enhancement after systemic delivery while sparring surrounding normal brain tissues.
Evaluation l'efficacité de la polypectomie par entéroscopie double ballon et analyse médico-économique
Authors: G Rahmi, MA Vinet, E Samaha, G Gay, K Vahedi, M Delvaux, H Lamouliatte, JC Saurin, T Ponchon, M Le Rhun, D Coumaros, P Bichard, T Manière, M Esvan, G Chatellier, C Cellier
Journal: Endoscopy (2015)

La polypectomie lors d'une entéroscopie double ballon (EDB) est devenu le traitement de première intention des polypes de l'intestin grêle. Notre objectif était 1/d'évaluer son efficacité et 2/d'estimer son coût total à 1 an par rapport au coût d'une prise en charge chirurgicale.
Case 30-2003
Authors: David N. Tancredi, Michael W. Shannon
Journal: New England Journal of Medicine (2003)

Presentation of Case Dr. Joshua N. Goldstein (Emergency Medicine): A 21-year-old man was brought to the emergency department because of a sudden change in mental status.On the evening of admission, the patient had been consuming alcohol with friends. They noted that he had begun to act strangely, becoming uncommunicative and incontinent of urine and stool, and thought that he might have had a brief seizure. They called an ambulance. When emergency medical services arrived, the patient was awake but uncommunicative and unable to follow commands. The glucose level in a finger-stick blood sample was normal. An intravenous catheter was . . .