tbuckley/cabot-search huggingface dataset:
Abstract 2699: Organ-specific signatures of melanoma metastasis.
Authors: Terje Sundstrøm, Lars Prestegarden, Clifford Tepper, Elizabeth Ingham, Lisa Even, Sarah Johnson, Kai Ove Skaftnesmo, Morten Lund-Johansen, Rolf Bjerkvig, Katherine Ferrara, Frits Thorsen
Journal: Cancer Research (2013)

Abstract We have previously reported on a reproducible and predictive animal model that can be used to elucidate the enigmatic biology of melanoma metastasis, a key prerequisite for therapeutic advances. Here, we have used this model to investigate the molecular drivers responsible for metastasis formation in different organs, with a special emphasis on brain-specific features. A human melanoma brain metastasis cell line (H1) was developed in our laboratory, transduced with the genes for green fluorescent protein and luciferase, and injected into the left cardiac ventricle of seven immunodeficient mice. Whole-body bioluminescence imaging (BLI) and brain magnetic resonance imaging was performed weekly to follow the development of metastases. The animals invariably developed both intracranial and extracranial tumors. At about seven weeks, the animals were euthanized and organ involvement was examined in detail by ex vivo BLI. The brain, femurs, adrenals, and ovaries from five random animals were enzymatically dissociated using organ-tailored protocols. Sample yield was validated by fluorescence microscopy prior to fluorescence-activated cell sorting of tumor cells. Three tumor cell samples from the brain, femurs, adrenals, and ovaries of different mice were then analyzed using next-generation RNA-sequencing (NGS) technology. We also performed baseline NGS on the H1 cell line before injection. Taken together, bioinformatics analysis revealed unique molecular signatures of organ-specific metastasis, validating some previously reported metastasis drivers and introducing other genomic features critical to the detrimental momentum of metastatic melanoma. Citation Format: Terje Sundstrøm, Lars Prestegarden, Clifford Tepper, Elizabeth Ingham, Lisa Even, Sarah Johnson, Kai Ove Skaftnesmo, Morten Lund-Johansen, Rolf Bjerkvig, Katherine Ferrara, Frits Thorsen. Organ-specific signatures of melanoma metastasis. [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 2699. doi:10.1158/1538-7445.AM2013-2699
Survival analisis in breast cancer's women in Santa Catarina, Brazil.
Authors: IJ Schneider, ED Orsi
Journal: Cancer Research (2009)

Abstract Abstract #6093 BACKGROUND: Overall survival after breast cancer diagnosis is influenced by the characteristics study's group, the study's place and biological factors.&amp;#x2028; OBJECTIVES: Define overall survival in five-years and the associated factors with the prognosis of breast cancer's women in Santa Catarina, Brazil.&amp;#x2028; MATERIALS AND METHODS: this is a historic cohort study, with data from diagnoses from January 2000 to December 2002 from Registro Hospitalar de Cancer of the Centro de Pesquisas Oncológicas,SC and the Hospital de Caridade, both in south Brazil, and complemented with data from the Mortality Information System until December 2007. The time of survival was calculated as the range of the date of diagnosis (biopsy or surgery) until the date of death or end of monitoring (5 years). The survival curves were estimated by the Kaplan-Meier method, using the log-rank test for comparison of the curves stratified. The effect of co-variable model was estimated by the semi-parametric risk proportionate, Model Cox, with the Schoenfelder analysis of residuals to assess whether the co-variables of the final model respect the principle of proportionality over time. The analysis was made using R 2.5.0.&amp;#x2028; RESULTS: 1002 women were included, and 262 deaths occurred, this 235 by breast cancer. The overall survival after 5 years was 76.2% (CI 95% 73,6-78,9%). Variables were associated with survival by the Kaplan-Meier curves: age, race/color, education, clinical stage, treatments received. This includes these variables in the model of Cox, remaining in the final model, as independent factors: age until 30 years (HR: 3,09, CI 95% 1,25-7,67); illiterate (HR 3,70, CI 95% 1,44-9,55); staging III (HR 5,27, CI 95% 2,56-10,82) and staging IV (HR 14,07, CI 95% 6,81-29,06); treatment with chemotherapy alone (HR 1,95, CI 95% 1,12-2,40), surgery, chemotherapy and radiotherapy (HR 2,38, CI 95% 1,36-4,16), compared to surgery and hormontherapy (HR 1.00). The Cox model variables respect the principle of proportionality over time (p=0,25).&amp;#x2028; CONCLUSIONS: The overall survival in breast cancer, proved to be better than in other Brazilian states. The instruction presents itself as a strong influence on survival, where illiterate women have worse prognosis. The combinations of treatment are also factors independent and influenced by biological factors. The diagnosis in advanced stages is one of the most important factors for worse survival, and modifiable through campaigns of early detection and mammography screening. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6093.
Abstract 764: Transient up-regulation of Myc in B-cell lymphomas enhances p53-independent apoptotic responses to chemotherapy.
Authors: Elena Sotillo-Piñeiro, Andrei Thomas-Tikhonenko
Journal: Cancer Research (2013)

Abstract The c-MYC oncogene deregulation is a common trait in human cancers, with programmed cell death (or apoptosis) among Myc-regulated events. Myc is well-known to induce apoptosis in a p53-dependent manner, via the Myc→ARF ┤MDM2 ┤p53 pathway. We had previously shown that this pathway couldbe exploited to increase sensitivity to anti-cancer drugs. Specifically, small increases in Myc levels obtained by inhibiting Myc-targeting microRNA-34a resulted in enhanced apoptotic response of B-cells to bortezomib (Sotillo et al, Oncogene 2010). Because many Myc-driven tumors are defective for p53 activity, we sought to determine whether transient up-regulation of Myc also increases cell death in response to chemotherapeutic drugs in a p53-deficient background. For this purpose, we used B-lymphoma cells isolated from bone marrows of p53ER™ knock-in mice and subsequently transduced with a Myc-expressing retrovirus (Amaravadi et al, J Clin Inv 2007, Yu et al, Blood 2007). This inducible system allowed us to distinguish between p53-dependent (cells treated with tamoxifen) and independent (no tamoxifen added) cell death. Additionally, instead of modulating Myc levels through miRNA inhibitors, which currently have limited clinical utility, we increased Myc stability with a small molecule inhibitor of GSK3β, which promotes proteosomal degradation of Myc. We observed that the activation of p53 via the addition of tamoxifen is sufficient to induce robust apoptosis, with neither modulation of Myc levels nor additional treatment with doxorubicin being necessary. On the other hand, in the absence of active p53 doxorubicin was needed to kill Myc/p53ER™ cells, but cell killing was rather inefficient. Remarkably, pharmacological stabilization of Myc strongly enhanced p53-independent doxorubicin-induced apoptosis. This enhancement was accompanied by selective activation of pro-apoptotic genes BIM, BAX and BAK, but not PUMA or NOXA, suggesting that the response was indeed p53-independent. To validate this effect in a more relevant setting, we inhibited GSK3β in various Burkitt's lymphoma cell lines and achieved consistent up-regulation of Myc. Most importantly, even in p53mut Ramos cells, Myc stabilization resulted in sharply increased responses to doxorubicin. Our results suggest that transient up-regulation of Myc could be a viable adjuvant therapy even for tumors with p53 loss or MDM2 amplification. Citation Format: Elena Sotillo-Piñeiro, Andrei Thomas-Tikhonenko. Transient up-regulation of Myc in B-cell lymphomas enhances p53-independent apoptotic responses to chemotherapy. [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 764. doi:10.1158/1538-7445.AM2013-764
Clinical Implications of Extragonadal Estrogen Production
Authors: N. Kase, G. L. Cohn
Journal: New England Journal of Medicine (1967)

INVESTIGATION of the daily production of androgen and estrogen by human beings has generated clinically important new concepts. It has been shown that both these groups of hormones may be synthesized by all endocrine tissues.1 In addition to the organ traditionally viewed as the primary secretor of a particular hormone, increments of varying magnitude will result from extragonadal biosynthesis. Although this supplementation is not considered significant in normal circumstances, its import is apparent in the manifestations of adrenocortical and ovarian disease.However, the availability of a particular hormone is not the result of endocrine secretion alone. The contribution of organ . . .
P253 NVA237 once daily offers rapid and clinically meaningful bronchodilation in COPD patients that is maintained for 24 h: the GLOW1 trial
Authors: T. D'Urzo, G. Ferguson, C. Martin, V. K. T. Alagappan, D. Banerji, Y. Lu, R. Horton, T. Overend
Journal: Thorax (2011)

<h3>Introduction</h3> NVA237 (glycopyrronium bromide) is an inhaled long-acting muscarinic antagonist (LAMA) in development for the once-daily (qd) treatment of COPD. The GLOW1 study evaluated the efficacy and safety of NVA237 in patients with moderate-to-severe COPD. <h3>Methods</h3> Patients were randomised (2:1) to 26 weeks double-blind treatment with NVA237 50 μg qd or placebo (PBO). Study drugs were administered via a single-dose dry powder inhaler (Breezhaler<sup>®</sup> device). Primary efficacy endpoint: trough FEV<sub>1</sub> (mean of 23 h 15 min and 23 h 45 min post-dose values) vs PBO after 12 weeks. <h3>Results</h3> 822 patients were randomised; mean age was 63.9 years, mean post-bronchodilator FEV<sub>1</sub> was 55% predicted. 80.5% completed the study. At Week 12 there was a statistically significant and clinically relevant difference between NVA237 vs PBO in mean trough FEV<sub>1</sub> (108 ml; p&lt;0.001). Trough FEV<sub>1</sub> was also significantly higher at Day 1 and Week 26 (treatment difference: 105 ml and 113 ml, respectively; p&lt;0.001). Serial spirometry in a subpopulation of patients showed statistically superior (p&lt;0.001) and clinically meaningful improvements in FEV<sub>1</sub> with NVA237 vs PBO at all timepoints on Day 1, Week 12 and Week 26. NVA237 had a rapid onset of action with an increased FEV<sub>1</sub> of 93 ml at 5 min and 144 ml at 15 min vs PBO after the first dose on Day 1 (p&lt;0.001). Overall, the incidence of adverse events (AEs) was similar between treatment groups (NVA237: 57.5%; PBO: 65.2%). Serious AEs were reported by 7.5% of NVA237- vs 9.0% of PBO-treated patients. <h3>Conclusion</h3> NVA237 50 μg once daily was generally safe and well tolerated. Improvements in bronchodilation were rapid, clinically meaningful and maintained for 24 h throughout the study.
Apport de l'infundibulotomie précoce dans les CPRE difficiles: une étude prospective
Authors: R Alhameedi, A Di Fiore, A Gangloff, L Thomassin, B Haddouche, P Michel, P Ducrotte, S Lecleire
Journal: Endoscopy (2015)

Le cathétérisme difficile de la voie biliaire principale (VBP) reste un problème fréquent dans la CPRE (environ 10-25% selon les études). Il existe plusieurs techniques endoscopiques utilisées pour le cathétérisme difficile de la VBP, incluant notamment la pré-coupe-sphinctérotomie et l'infundibulotomie ou fistulotomie supra-papillaire. Toutefois, le taux de complications avec ces techniques de CPRE avancées semble être plus élevé que pour les patients qui ont bénéficié d'une sphinctérotomie conventionnelle. Certaines études ont identifié l'infundibulutomie comme un facteur de risque indépendant de complications sévères post-CPRE. Cependant, l'infundibulotomie est souvent utilisée tardivement après un temps de cathétérisme conventionnel très variable selon les études, généralement supérieur à 15 minutes. Le but de notre étude était d'évaluer prospectivement:
PROSPECTIVE EVALUATION OF THE IMPACT OF SIDE-HOLES AND GUIDE CATHETER DISENGAGEMENT FROM THE CORONARY OSTIUM ON FRACTIONAL FLOW RESERVE MEASUREMENTS
Authors: Krishna Patel, Georgios Christakopoulos, Aris Karatasakis, Barbara Anna Danek, Phuong-Khanh Nguyen-Trong, Suwetha Amsavelu, Jeffrey Stetler, Bavana Rangan, Michele Roesle, Shuaib Abdullah, Tayo Addo, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2016)
AB0397 Carotid atherosclerosis and metabolic syndrome in patients with rheumatoid arthritis
Authors: L. Kondratyeva, E. Gerasimova, T. Popkova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cardiovascular morbidity and mortality in patients with rheumatoid arthritis (RA) is associated with early atherosclerosis. A possible explanation could be the metabolic syndrome (MetS) and inflammation. <h3>Objectives</h3> To evaluate MetS prevalence and the preclinical atherosclerosis in patients with RA. <h3>Methods</h3> Two hundred twenty-five patients with RA (190 woman, 35 men) aged 18-59 years were included in this cross-sectional study, 79% of them had positive rheumatoid factor. MetS prevalence was assessed using NCEP ATPIII (2004) definitions (at least three of five characteristics: abdominal obesity, low level of high density lipoproteins cholesterol, elevated triglyceride and fasting glucose levels, high blood pressure). Carotid intima-media thickness was examined by high resolution B-mode ultrasound measurements. Atheromatous plaque was defined as a local intima-medial thickening ≥1,2mm. The levels of CRP and inflammatory cytokine (interleukin - 18) were determined in serum samples by the high sensitive particle-enhanced immunonephelometric assay. <h3>Results</h3> MetS was found in 49 (22%) patients with RA (obesity - 39%, low level of high density lipoproteins cholesterol - 56%, elevated triglyceride level - 10%, elevated fasting glucose level - 14%, hypertension - 54%). Patients with MetS were older (52 years versus 48 years without MetS, p=0,003) but had lower RA duration (54 months versus 120 months without MetS, p=0,02). No difference was observed in ESR, CRP levels and DAS28 in groups with and without MetS. Glucocorticoids use did not associate with MetS. Patients with MetS had significantly higher prevalence of carotid plaques (38% versus 20% in patients without MetS, p=0,01), maximal carotid intima-media thickness (1,0 (0,9-1,2)mm versus 0,9 (0,8-1,0)mm, p=0,007) and level of interleukin-18 (79,5 (0,01-213) pg/ml versus 40 (0,01-393) pg/ml, p=0,05). <h3>Conclusions</h3> Most frequently criteria of MetS in patients with RA are dyslipoproteinemia and hypertension. MetS is associated with preclinical atherosclerosis and higher level of proinflammatory interleukin-18. <h3>Disclosure of Interest</h3> None Declared
PWE-183 Survivin expression increases in the progression to oesophageal adenocarcinoma
Authors: I Puccio, MA Butt, M Rodriguez-Justo, S-U-R Khan, V Sehgal, M Novelli, LB Lovat, R Hamoudi
Journal: Gut (2015)

<h3>Introduction</h3> It has been postulated that the process of apoptosis leads to the development of neoplastic clones with prolonged survival. Survivin, an inhibitor of apoptosis, is an integral to this process. The primary aim of this study is to examine the expression of Survivin in the progression from Barrett’s Oesophagus (BO) to oesophageal adenocarcinoma (OAC). <h3>Method</h3> Endoscopic biopsies containing the relevant pathologies from 72 patients were immunostained for Survivin expression - normal squamous (Sq) 14, non-dysplastic BE (NDBE) 14, low-grade dysplasia (LGD) 17, high-grade dysplasia (HGD) 17 and oesophageal adenocarcinoma (OAC) 7. Survivin expression was scored by 2 expert GI pathologists using the Allred system (a score comprising both intensity and extent of staining) and analysed using one-way ANOVA with Bonferroni post-hoc analysis to examine the trend between the various groups in the upper GI sequence. <h3>Results</h3> Multivariate analysis using one-way ANOVA and Bonferroni post-hoc analysis showed a strongly significant increase in both intensity and extent of Survivin expression in the progression from squamous, through non dysplastic Barrett’s oesophagus, low-grade dysplasia, high-grade dysplasia and invasive adenocarcinoma (OAC) p &lt; 0.0001 for both analyses. Allred scores also rose incrementally through the progression sequence, with a mean score of 1.7 in squamous, 2.8 in NDBE, 3.8 in LGD, 5.2 in HGD and 6.1 in cancer (p &lt; 0.0001). <h3>Conclusion</h3> This study shows that Survivin expression follows a linear incremental up-regulation in the progression to OAC. This early up-regulation suggests increasingly prominent roles for apoptosis inhibition in this pathway. In addition, the results suggest that inhibitors of Survivin might play a role in the prevention of progression as well as the treatment of OAC. <h3>Disclosure of interest</h3> None Declared.
Serendipitous Detection of Thyroid Carcinoma in a Patient With Graves' Disease
Authors: MASOOD AHMAD, WILLIAM JOHNS, SHIV M. GUPTA
Journal: Clinical Nuclear Medicine (1999)

A cold thyroid nodule was detected in a diffusely enlarged gland in a patient undergoing thyroid uptake and scan for suspected Graves' disease. Fine-needle biopsy of the nodule suggested neoplasm. Subsequent surgery confirmed the diagnosis of papillary carcinoma of the thyroid. The patient was treated successfully for both Graves' disease and papillary carcinoma of the thyroid with total thyroidectomy.
Near patient tests are poorly evaluated
Authors: H. Bower
Journal: BMJ (1997)

New technologies that make laboratory tests and results immediately available to patients in primary care have leapt far ahead of concrete data on benefits, an expert review group claims.

The report from the NHS Research and Development Health Technology Assessment Group, which provides doctors with evidence based assessments of the cost, effectiveness, and impact of new technologies, concluded that there was “little evidence to support the general introduction of near patient testing in preference to existing laboratory …
A Case of Malignant Lymphoma with Breast and Ovary Involvement as a Cause of Fever of Unknown Origin Detected by Ga-67 Scintigraphy
Authors: Hitoya Ohta, Masayuki Shintaku, Takao Himeno, Tsuneshi Nakano, Takao Takeuchi
Journal: Clinical Nuclear Medicine (2002)

OHTA, HITOYA M.D.; SHINTAKU, MASAYUKI M.D.; HIMENO, TAKAO M.D.; NAKANO, TSUNESHI; TAKEUCHI, TAKAO M.D. Author Information
Reply to Ustundag
Authors: M. Hocke, A. Ignee, C. Dietrich
Journal: Endoscopy (2011)

According to our experience and follow-up studies (not published to date), and with regard to published articles, it is our feeling that focal and diffuse autoimmune pancreatitis (AIP) are stage-dependent and both stages could be seen as a continuum with overlap. In our study, therefore, patients with focal as well as those with diffuse AIP were included. It could be shown in patients with focal AIP that the elastographic pattern of the remaining pancreatic tissue is homogeneously stiff (hard), which can be used as a diagnostic sign [1]. In addition, we could show that the vascularization and perfusion pattern of the inflammatory tissue really does not matter in the earlier stages. In the end-stage disease, only fibrotic and sclerotic tissue is present but such patients were not included in our study. A prospective multicenter study investigating the stage-dependent diagnosis of AIP would provide useful information in this regard.
CONSIDERATIONS IN THE DEVELOPMENT OF AN 131-I-MIBG THERAPY PROGRAM FOP ADVANCED NEUROBLASTOMA.
Authors: J. Huberty, K. Matthay, B. Engelstad, R. Hattner, Y. Yano, T. Budinger, A. Ablin
Journal: Clinical Nuclear Medicine (1986)

Huberty, J.; Matthay, K.; Engelstad, B.; Hattner, R.; Yano, Y.; Budinger, T.; Ablin, A. Author Information
Abstract 534: Protein kinase c ≤ cooperates with Pten deficiency in prostate cancer progression
Authors: Rachana Garg, Jorge Blando, Carlos J. Perez, Fernando Benavides, Marcelo G. Kazanietz
Journal: Cancer Research (2012)

Abstract Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related deaths among men. Protein kinase C epsilon (PKC∈), a member of the PKC family of phorbol ester/diacylglycerol receptors, has been shown to be up-regulated in human prostate cancer specimens. We recently demonstrated that mice that specifically overexpress PKC∈ in prostate under the control of the probasin promoter (PB-PKC∈) develop hyperplasia and PIN lesions. However, PKC∈ overexpression was insufficient to drive neoplastic changes in the mouse prostate. In the present study our goal was to determine whether PKC∈ overexpression can cooperate with Pten deficiency, one of the most common genetic alterations in human prostate cancer. We stably overexpressed PKC∈ in two pairs of isogenic mouse prostate epithelial lines that are either heterozygous (P2, P8) or homozygous (CaP2, CaP8) for Pten deletion. PKC∈ overexpression led to significant enhancement in cell proliferation compared to the respective control cells and this effect is more pronounced in CaP2 or CaP8 cells. Moreover, assays of colony formation in liquid medium revealed that anchorage-dependent growth was augmented in PKC∈-overexpressing cells relative to control cells. A significant elevation in phospho-Akt levels was observed in PKC∈ overexpressing cells relative to respective controls. To further elucidate the cooperativity between PKC∈ overexpression and Pten loss we intercrossed the PB-PKC∈ transgenic mice and Pten+/− mice. Strikingly, the resulting compound mutant mice overexpressing PKC∈ and haploinsufficient for Pten (PB-PKC∈; Pten+/−) developed fully invasive adenocarcinoma at 12 months of age. Very strong phospho-Akt, phospho-S6 and phospho mTOR staining could be detected in adenocarcinomas from PB-PKC∈; Pten+/− mice. Furthermore, we detected enhanced p-Erk, Cox-2, STAT3, NF-κB and cyclin D1 signaling in adenocarcinomas from PB-PKC∈;Pten+/− mice than in lesions from each monogenic model. These data thus suggest that PKC∈ overexpression cooperates with a defined oncogenic input to promote prostate tumorigenesis. These findings also suggest a crucial role of PKC∈ in survival. 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 534. doi:1538-7445.AM2012-534
Letter to the editor: Salmonella Stanley outbreaks – a prompt to reevaluate existing food regulations
Authors: B Springer, F Allerberger, C. Kornschober
Journal: Eurosurveillance (2014)

Preview this article: Letter to the editor: Salmonella Stanley outbreaks – a prompt to reevaluate existing food regulations, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/19/22/art20818-en-1.gif
Case 8-1997
Authors: Timothy C. Wang, Lawrence R. Zukerberg
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 65-year-old man was admitted to the hospital because of severe abdominal pain and recurrent diarrhea.The patient had been well until five years earlier, when he and his wife had nausea, vomiting, and diarrhea after consuming meat in Istanbul, Turkey. The patient took bismuth tablets, and his symptoms resolved in three days. Thereafter, he had bouts of mild abdominal pain and diarrhea about once a month. His wife remained well after the initial episode. Four years before admission, the patient's pain became more severe, with occult blood in the stools. A colonoscopic examination showed two benign . . .