tbuckley/cabot-search huggingface dataset:
Abstract 2815: Sylvestrol inhibits protein synthesis by downregulating the AKT/mTOR pathway
Authors: Jilai Yang, Qi Shen, David J. Newman, A. Douglas Kinghorn, Steven M. Swanson
Journal: Cancer Research (2012)

Abstract Silvestrol, a cyclopenta[b]benzofuran lignan present in the fruits and twigs of the tropical tree Aglaia foveolata Pannell (Meliaceae), is toxic to human cancer cell lines in culture with a potency similar to those of FDA approved anticancer chemotherapeutic agents. We report here that silvestrol has a mean GI50 of approximately 3 nM in the 60 cell-line panel of human cancer cell lines maintained at the National Cancer Institute. Furthermore, silvestrol is at least as effective as FDA-approved anticancer agents in the treatment of human cancer cells in vivo when tested in the hollow fiber assay or the inhibition of human tumor xenograft tumors propagated in immunedeficient mice. Others as well as our group have reported that silvestrol inhibits protein biosynthesis specifically without affecting the cellular production of either RNA or DNA. Pelletier and colleagues have shown that silvestrol impairs the ribosome recruitment step of translation initiation by affecting the composition of the eukaryotic initiation factor (eIF) 4F complex. In the present study, we test the hypothesis that disruption of protein synthesis by silvestrol can impact cell signaling pathways upstream of translation. Human colon cancer cells designated HT-29 were exposed to silvestrol at concentrations as high as 100 nM for as long as 48 h prior to harvest and evaluation by immunoblot. Protein signaling molecules known to regulate the protein synthesis machinery were evaluated for their abundance and state of phosphorylation as a function of silvestrol exposure. We observed down-regulation of the p110α catalytic subunit of PI3K, which phosphorylates PIP2 to PIP3. PIP3 then recruits PDK1 and AKT to the plasma membrane, where PDK1 can phosphorylate AKT. A decrease in the amount of PDK1 protein and a significant decrease in phosphorylation of AKT at ser 473 occurred. Moreover, a decrease in both the abundance and phosphorylation of mTOR was evident, which is a key component of mTORC2. Consistent with these findings, phosphorylation of AKT at thr 308 was significantly reduced. Finally, silvestrol exposure resulted in a decrease in phosphorylation of the S6 ribosomal protein serine 235/236. These data indicate that silvestrol treatment can disrupt key signaling pathways leading to protein synthesis production in human cancer cells. This work was supported by NIH grants U01 CA52956 and P01 CA125066. 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 2815. doi:1538-7445.AM2012-2815
SP0150 The Care of Teenagers with JIA - Efforts Done to Improve the Transition Process in Finland
Authors: M. Backström
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> During the last years many efforts have been done to improve the transition process in Finland. The routines differ throughout the country and these different routines are presented. In many centres we start preparing the youngsters at the age of 12-13 years. We invite them into the examination room without parents. After the examination the parents are welcomed into the room for discussion. Transition readiness checklists are used. Special transition days are arranged. At some centres a Web-based evaluation of the guidance given at the paediatric clinic is performed at the first visit at the adult clinic. The goal is to prepare the teenagers gradually and according to their psychological development. <h3>Disclosure of Interest</h3> M. Backström Grant/Research support from: Cost of medical congresses by Pfizer and AbbVie <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6107
P71 A model to improve performance of current category 9 UK listing criteria: early liver graft dysfunction. A single centre cohort
Authors: M. A. B. Al-Freah, E. Dionigi, M. J. W. McPhail, M. Foxton, G. Auzinger, M. Rela, N. D. Heaton, J. G. O'Grady, M. A. Heneghan, W. Bernal, J. A. Wendon
Journal: Gut (2011)

<h3>Introduction</h3> Current super urgent criteria for listing for early liver graft dysfunction (ELGD) in the UK (category 9, C9C) is defined as fulfilling 2 out of 4 of the following criteria within 7 days post liver transplant (LT): AST &gt;10 000IU/l, INR &gt;3, Lactate &gt;3 mmol/l and absence of bile production. We demonstrated that these criteria have critically low sensitivity in predicting early post LT death or need for re-LT (Al-Freah, <i>et al. Hepatology</i> 2009;<b>50</b> Suppl 4:A148). <h3>Aim</h3> To develop an improved predictive model for early re-LT or death using early post-LT clinical parameters. <h3>Method</h3> Retrospective study of all patients transplanted at our centre 1 January 2000 to 31 December 2008. Daily clinical and laboratory parameters for the first 7 days post LT were reviewed. These included AST, bilirubin, INR, lactate, vasopressor requirement and/or haemofiltration. <h3>Results</h3> Over the study period, 1286 patients underwent first LT at our centre. Patients excluded (28) because of re-LT for hepatic artery thrombosis (22), died on table (5) and one re-LT because of donor cancer. We analysed data on 1258 patients (median age 51 (16–74) years (16–74), 60% male). The most common aetiology was viral hepatitis in 303 patients (24%) and alcohol related liver disease in 227 patients (18%); 181 patients (14.4%) with hepatocellular carcinoma. Median MELD score was 16 (6–40). Death or re-LT rate at 3 months was 9.9% (124). Only 27 (2.1%) fulfilled C9C at 3 months: 17 (63%) of those died or had re-LT within 3 months (p&lt;0.001). C9C had sensitivity of 14% (9.8–17%), specificity 99% (98–99%), positive likelihood ratio (LR+) 15.533 (7.41–32.73) and negative likelihood ration (LR−) 0.87 (0.83–0.91). Abstract P71 table 1 shows the univariate and multivariate analyses of predictors of 3 months liver-related death or re-LT using Cox regression hazard method. Accordingly, we generated a model comprises any 1 of the following 5 to predict ELGD and death or re-LT: vasopressor requirement at day D7, D1 lactate &gt;3 mmol/l, D7 AST &gt;500 IU/l and D7 bilirubin &gt;100 μmol/l. Those scored 1, 2, 3, 4 or 5 points had OR of risk of death/re-LT within 3 months of 1.26 (0.897–1.766, p=0.184), 1.345 (0.8817–2.051, p=0.171), 2.811 (1.669–4.732, p=0.0001), 15.561 (7.425–32.611, p&lt;0.0001) and 36.509 (13.188–101.074, p&lt;0.0001), respectively. 85 of 124 patients who had a 3 month liver related outcome met this criterion compared to 16 who met C9C. This gave sensitivity 68% (58–77%), specificity 67% (64–70%), LR+ 2.08 (1.77–2.45) and LR− 0.48 (0.36–0.63). <h3>Conclusion</h3> The new model is simple to use and significantly improved the sensitivity of detection of severe ELGD. Validation in another cohort of LT patients is warranted.
Abstract 5071: The genomic landscape of pancreatic cancer: from discovery to patient care
Authors: Andrew V. Biankin, Sean M. Grimmond
Journal: Cancer Research (2012)

Abstract Pancreatic Cancer is the fourth leading cause of cancer death in our society, with a mortality that virtually parallels its incidence, a median survival of &amp;lt; 12 months even with maximal therapy, and a 5-year survival rate of &amp;lt; 5%. The diversity of clinical outcomes and the molecular heterogeneity of histopathologically similar cancer types, incomplete knowledge of the genomic aberrations that drive carcinogenesis and the lack of therapeutics that specifically target most known genomic aberrations necessitates large scale detailed analysis of cancer genomes to identify novel potential therapeutic strategies. As part of the International Cancer Genome Consortium (ICGC), the Australian Pancreatic Cancer Genome Initiative (APGI), together with the Baylor College of Medicine and the Ontario Institute of Cancer Research used exomic sequencing and copy number analysis to define genomic aberrations that characterise a large clinically focused prospectively accrued cohort of patients with pancreatic cancer (n = 142). The cohort consists of early (clinical stages I and II) non-pretreated patients with pancreatic ductal adenocarcinoma who underwent operative resection with curative intent. We devise approaches to adjust for low epithelial content in primary tumours and define the genomic landscape of pancreatic cancer to identify novel candidate driver genes and mechanisms. We develop stratified, molecular phenotype guided therapeutic strategies using existing therapeutics that are either rescued, repurposed, in development, or are known to be effective in an undefined subgroup of PC patients. These are then tested in primary patient derived xenografts and cell lines from the above deeply characterised cohort. In addition, we are launching a clinical trial named IMPaCT (Individualised Molecular Pancreatic Cancer Therapy). This trial randomises patients with metastatic disease to either standard first line therapy with gemcitabine, or a molecular phenotype guided approach using next generation sequencing strategies to screen for actionable mutations defined through the ICGC effort. 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 5071. doi:1538-7445.AM2012-5071
Abstract 1265: Sustained PI3-kinase signaling is mediated by ICOS, not CD28, for anti-tumor T-cell responses elicited by anti-CTLA-4.
Authors: Hong Chen, Tihui Fu, Dimitra Tsavachidou, Sijin Wen, Derek Ng Tang, Qiuming He, Jing Jing Sun, Padmanee Sharma
Journal: Cancer Research (2013)

Abstract The generation of anti-tumor T-cell responses requires at least two distinct signals consisting of T-cell receptor signaling and CD28-costimulation to mediate PI3-kinase signaling. In previous studies, we reported that cancer patients treated with anti-CTLA-4 had a significant increase in T-cells expressing inducible costimulator (ICOS). Here, we observed that PI3-kinase signaling was significantly increased in ICOShi as compared to ICOSlow CD28+ T-cells from anti-CTLA-4 treated patients. Our data also indicate that after T-cell activation, ICOS-mediated PI3-kinase signaling plays an important role in downstream T-cell responses such as expression of the T-bet transcription factor and anti-tumor Th1 cytokine production. An ICOS-specific siRNA transfected into activated human T-cells leads to diminished PI3K-signaling and T-bet expression, which controls production of anti-tumor Th1 cytokines. Furthermore, T-cells from ICOS-deficient mice have impaired PI3-kinase signaling after in vitro activation. Our data also demonstrate that T-cells from ICOS-deficient mice have impaired PI3-kinase signaling in vivo, which correlates with impaired tumor rejection after treatment with anti-CTLA-4. These data offer strong evidence to support that CD28-mediated PI3-kinase signaling is limited and ICOS provides a critical third signal to enable sustained PI3-kinase signaling for optimal anti-tumor T-cell responses in the setting of anti-CTLA-4 therapy. Citation Format: Hong Chen, Tihui Fu, Dimitra Tsavachidou, Sijin Wen, Derek Ng Tang, Qiuming He, Jing Jing Sun, Padmanee Sharma. Sustained PI3-kinase signaling is mediated by ICOS, not CD28, for anti-tumor T-cell responses elicited by anti-CTLA-4. [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 1265. doi:10.1158/1538-7445.AM2013-1265
FRI0404 Contributions of the New SLICC 2012 Classification Criteria for Systemic Lupus Erythematosus (SLE): What Kinds of Patients Are Rescued?: Table 1
Authors: I. Rúa-Figueroa, F. Perdomo, C. Erausquin, M. García-Bello, S. Ojeda, F. Francisco, A. Naranjo, J.C. Quevedo, L. Cáceres, C. Rodriguez-Lozano
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To contribute towards characterizing SLE patients as defined by the new SLICC classification criteria (ncSLICC) in comparison with patients defined by classic criteria (ACR-97). <h3>Methods</h3> a retrospective study on a large monocentric cohort of well characterized patients with SLE was carried on, estimating the percentage of patients who meet the ncSLICC and comparing patients with probable SLE (&lt;4 criteria ACR97) (pSLE) redefined as SLE with ncSLICC versus those defined by the ACR97 criteria (≥4criteria) (dSLE). We collected and compared the demographic and clinical characteristics, damage index (SDI), severity Katz index (SKI), major organ involvement, hospitalization, mortality and cumulative treatments data. <h3>Results</h3> All pSLE patients of our cohort (N=39), 9.7% of the total (N=403), were included as well as a random sample of 169 controls with dSLE (41.4% of total cohort of dSLE, N=364); 48 patients did not fulfill the criteria of ACR-82, 18.7% (N=9) of them were rescued as SLE by the ACR-97 criteria, reducing pSLE to 39 patients. 100% of the patients whom met the ACR-97 criteria met also ncSLICC, being estimated that 96.5% of our full cohort (N=403) fulfil the ncSLICC. The frequencies of the different criteria are shown in table1 (data no shown in the abstract); 64% (N=25) (95%CI: 0.47-0.78) of the pSLE met the ncSLICC. The pSLE patients who met ncSLICC are milder than patients with dSLE, with SDI of 0.4 (±56) vs. 1.95 (±2.4) (p&lt;0,001) and SKI of 0.8 vs. 3.7 (±2.4) (see table 2 for all other comparisons), although the duration of disease was higher in dSLE. Matching the 25 pSLE patients who meet ncSLICC with 25 dSLE patients and same duration of the disease (1:1), statistical significance remained for SKI difference (0.8±0.65 vs. 3.32±2.63; p&lt;0.001) and major organ involvement [1 (4.2%) vs. 9 (36%) (p=0.010)]. <h3>Conclusions</h3> 1. The vast majority of definite SLE patients (ACR-97 criteria) also meet the new SLICC group classification criteria. 2. The new SLICC criteria rescues a significant percentage of patients with incomplete (or probable) SLE, while predominantly incorporating less severe patients. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4762
Unexpected Gallbladder Emptying From Visual Stimulation
Authors: Mark Tulchinsky
Journal: Clinical Nuclear Medicine (2011)

Unexpected (without deliberate stimulation) emptying of a gallbladder (GB) during hepatobiliary scintigraphy is rare. Such a case is presented where the patient was watching a movie that contained episodes of appetizing meal preparation and consumption. The photic stimulation was recognized and discontinued, resulting in the GB refilled after a 15-minute wait. The GB ejection fraction was then obtained after cholecystokinin stimulation and was similar to unexpected emptying. In conclusion, it is prudent to limit all possible stimulating factors during hepatobiliary scintigraphy, including thought, sight, smell, taste, mastication, and swallowing of food.
EUS-FNA of the left adrenal gland-diagnostic yield and complications
Authors: TL Ang, S Seewald, S Omar, F Dy, N Soehendra
Journal: Endoscopy (2006)

Background: There are limited published data on the clinical utility and safety of endososcopic ultrasound (EUS)-guided fine needle aspiration (FNA) of the left adrenal gland. This study examined the diagnostic yield and safety of EUS-FNA of left adrenal masses at a single referral centre. Methods: Patients with an enlarged left adrenal gland diagnosed on abdominal imaging or during tumor staging and who were referred for EUS-guided FNA from Nov 1996 to May 2005 were included. The diagnostic yield, complication rate and features predictive of malignancy were examined. Results: Thirty-six consecutive patients were evaluated. EUS-FNA was not performed in 2 patients due to suspected phaeochromocytoma. Thirty-four patients (24 male, 10 female; mean age 67 years) underwent EUS-FNA and were analyzed. The indications were isolated left adrenal mass (9) and possible left adrenal metastases in suspected (6) or confirmed malignancies (19). Adequate tissue specimens were obtained in all cases. The median number of needle passes was 1 (1–2). There were no procedure-related complications. Among patients with confirmed underlying malignancies, adrenal metastases were diagnosed in 14/19 and adrenal adenoma in 5/19. Among isolated left adrenal masses, adenoma was present in 8/9, with one case of adrenal carcinoma. Features predictive of malignant cytology were larger size (38.2 vs. 17.9mm; p=0.01), loss of normal adrenal outline (OR 11.4; 95% CI 1.6–83.3) and presence of extra-adrenal malignancies (OR 10.3; 95% CI 1.5–71.4). Conclusion: EUS-guided FNA is a safe and highly accurate method to determine the nature of an isolated left adrenal mass and to confirm adrenal metastases. A larger size, loss of normal adrenal outline and presence of extra-adrenal malignancies are suggestive of a malignant adrenal mass, but FNA is required for definitive diagnosis.
Abstract B1-01: Whole genome expression based drug repurposing
Authors: Paul Geeleher, Steven Bhutra, Jacqueline Wang, R. Stephanie Huang
Journal: Cancer Research (2015)

Abstract Currently, personalizing cancer chemotherapy relies on pathology and more recently molecular biomarker-based approaches. However, as the driving biology is normally not fully understood, the majority of existing biomarkers do not capture a substantial proportion of variability in drug response. This partly explains the commonly observed lack of reproducibility of findings (e.g. from many conventional gene expression signatures) when these markers are applied to new datasets. We developed an approach to predict in vivo drug sensitivity that leverages whole-genome gene expression microarray data and allows the expression of every gene to influence the prediction by a small amount. Our approach builds statistical models from gene expression and drug sensitivity data in a very large panel of cell lines, then applies these models to gene expression data from primary tumor biopsies. In this study, we applied this approach to tumor samples collected in The Cancer Genome Atlas (TCGA). We derived predicted sensitivity for over one hundred drugs in each of the tumor samples. As a proof-of-concept, we demonstrated that a targeting agent (lapatinib) designed against a specific tumor marker (HER2 positive) is indeed predicted to be more sensitive in HER2 positive breast cancers when compared to the other type of cancers. Meanwhile, we identified other agents that exhibit similar or superior sensitivity when compared to commonly prescribed agents in different disease settings. These findings warrant further evaluation of these agents to be repurposed for possible new indications. Interestingly, some of our derived drug sensitivity predictive estimates are correlated with observed survival outcomes in certain cancer patients. When screening all tumor types based on their molecular profiles, we defined several classes of drugs that maybe differentially effective based on tumor molecular profiles. In conclusion, a genome-wide expression drug sensitivity model built in cell lines can be a powerful approach in repurposing drug in cancer treatment. Citation Format: Paul Geeleher, Steven Bhutra, Jacqueline Wang, R. Stephanie Huang. Whole genome expression based drug repurposing. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B1-01.
Syndromes Associated with Allergic Vasculitis
Authors: Robert P. McCombs, James F. Patterson, H. E. MacMahon
Journal: New England Journal of Medicine (1956)

VASCULITIS denotes inflammation within the walls of blood vessels; it develops as a nonspecific reaction to various stimuli, including trauma, infection, thrombosis, embolization and hypersensitivity; it is also seen adjacent to some tumors, in eruptive xanthomatoses and in severe hypertensive states. In the absence of pathological evidence that active vasculitis is secondary to some other disorder, the possibility of an allergic origin must be seriously considered. Proof of allergic etiology in a given case, however, is difficult because of the lack of suitable immunologic technic.There is ample experimental and clinical evidence that small blood vessels may be involved in . . .
Endobrachyoesophage avec dysplasie de haut grade et carcinome in situ. Résultats à long terme chez 106 patients
Authors: C Loeve
Journal: Endoscopy (2011)

Introduction: La problématique de l'endobrachyoesophage (EBO) réside dans son risque de transformation en adénocarcinome dont l'incidence est en forte augmentation ces 20 dernières années dans les pays occidentaux. Il existe désormais une alternative au traitement chirurgical des dysplasies sévères et carcinomes in situ sur EBO: la mucosectomie endoscopique.
Safety first: the case against oral sodium phosphate
Authors: Supriya Rao, Audrey Calderwood
Journal: Endoscopy (2014)

Adequate bowel preparation is necessary for the successful completion of a high-quality colonoscopy. Good bowel preparation is associated with increased efficacy, decreased procedure times, increased adenoma detection rates, and fewer complications [1]. Despite the importance of bowel cleanliness in the performance of colonoscopy, bowel preparation is poor in up to 24 % of examinations [2].
Novel treatment of a gastric Dieulafoy lesion with an over-the-scope clip
Authors: V. Gómez, K. Kyanam Kabir Baig, F. Lukens, T. Woodward
Journal: Endoscopy (2013)

A 74-year-old man presented with recurrent obscure, overt, life-threatening gastrointestinal bleeding. Esophagogastroduodenoscopy (EGD) showed blood in the fundus and a nonbleeding Dieulafoy lesion at the lesser curvature of the stomach ([Fig. 1]). Due to the tangential position and large size of the lesion, thermal therapy or through-the-scope clipping were not carried out and an over-the-scope clip (Ovesco, Tübingen, Germany) was successfully deployed across the lesion ([Fig. 2]).
Abstract 308: Tumor hypoxia promotes tolerance and angiogenesis via CCL28 and Treg cells
Authors: Andrea Facciabene, George Coukos
Journal: Cancer Research (2012)

Abstract Although immune mechanisms can suppress tumor growth, tumors establish potent and overlapping mechanisms that mediate immune evasion. Emerging evidence suggests a link between tumor immune tolerance and angiogenesis. Hypoxia, a condition known to drive tumor angiogenesis, results in release of damage-associated molecular pattern molecules, which can trigger tumor immune rejection. Thus, counter-activation of tolerance mechanisms at the site of tumor hypoxia would be a critical condition to maintain immunologic escape of tumors. However, a direct link between tumor hypoxia and tolerance through the recruitment of regulatory cells has not been established. We hypothesized that tumor hypoxia induces expression of chemotactic factors promoting tolerance. Here we show that tumor hypoxia promotes T regulatory (Treg) cell recruitment via the CCL28 chemokine, which in turn promotes tumor tolerance and angiogenesis. Thus, peripheral immune tolerance and angiogenesis are intimately connected and cooperate to sustain tumor growth. 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 308. doi:1538-7445.AM2012-308
Milken Crusade Galvanizes Research On Prostate Cancer
Authors: J. Mathews
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Milken Crusade Galvanizes Research On Prostate Cancer Get access James Mathews James Mathews Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 12, 21 June 1995, Pages 873–875, https://doi.org/10.1093/jnci/87.12.873 Published: 21 June 1995