tbuckley/cabot-search huggingface dataset:
The biology and function of exosomes in cancer
Authors: Raghu Kalluri
Journal: Journal of Clinical Investigation (2016)

Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40-150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients.
OP0026 Diabetes Effects on Pain and Physical Function in Incidence and Progression Subcohorts of the Osteoarthritis Initiative: A 5-Year Longitudinal Data Analysis
Authors: I. Shirinsky, V. Shirinsky
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A number of epidemiological studies have shown a possible association between diabetes and osteoarthritis (OA). However, curently there is a lack of data on whether diabetes independently predicts pain and function deterioration in OA. <h3>Objectives</h3> To assess influence of diabetes on pain and function measures in patients with established knee OA and in subjects with increased risk of knee OA. <h3>Methods</h3> For the current study we used longitudinal data obtained from the Osteoarthritis Initiative (OAI) public use data set, which is available at http://oai.epi-ucsf.org. The OAI cohort consists of progression subcohort (patients with symptomatic tibiofemoral knee OA, n= 1390), incidence subcohort (subjects with increased risk of OA, n = 3284) and reference control subcohort (n=122). In the current analysis we used the longitudinal data from the both progression and incidence subcohorts. The selected outcome variables were Western Ontario McMaster Osteoarthritis Index (WOMAC), Knee Osteoarthritis Outcome Scale (KOOS) and timed 20 meter walk. Weight was measured using a balance beam scale, height was measured with a Stadiometer. The information on previously diagnosed diabetes was collected from the self-reported Charlson Comorbidity Index. All outcomes were assessed at baseline and years 1,2,3,4, and 5 except 20 meter walking test which had been performed yearly up to four year follow up. Generalized estimating equations (GEE) were used to model the relationship between outcomes measured over time and diabetes at study entry. The model was adjusted for demographic characteristics, prior knee surgery, baseline outcome pain or function measures, Physical Activity Scale for the Elderly, and body mass index. <h3>Results</h3> On baseline, 151 (10.9%) patients in progression subcohort and 210 (6.4%) patients in incidence subcohort reported diabetes. The results of GEE analysis (Table) shows that after adjusting for multiple covariates, diabetes significantly predicted the impairment of most of the outcome measures in both the incidence and progression subcohorts of OAI. <h3>Conclusions</h3> Diabetes is an independent predictor of longitudinal pain and function worsening in patients with symptomatic knee OA as well as in subjects who are at higher risk of knee OA development. <h3>Disclosure of Interest</h3> None Declared
APOL1-G0 or APOL1-G2 Transgenic Models Develop Preeclampsia but Not Kidney Disease
Authors: Leslie A. Bruggeman, Zhenzhen Wu, Liping Luo, Sethu M. Madhavan, Martha Konieczkowski, Paul E. Drawz, David B. Thomas, Laura Barisoni, John R. Sedor, John F. O'Toole
Journal: Journal of the American Society of Nephrology (2016)

APOL1 risk variants are associated with kidney disease in blacks, but the mechanisms of renal injury associated with APOL1 risk variants are unknown. Because APOL1 is unique to humans and some primates, we created transgenic (Tg) mice using the promoter of nephrin-encoding Nphs1 to express the APOL1 reference sequence (G0) or the G2 risk variant in podocytes, establishing Tg lines with a spectrum of APOL1 expression levels. Podocytes from Tg-G0 and Tg-G2 mice did not undergo necrosis, apoptosis, or autophagic cell death in vivo, even in lines with highly expressed transgenes. Further, Tg-G0 and Tg-G2 mice did not develop kidney pathology, proteinuria, or azotemia as of 300 days of age. However, by 200 days of age, Tg-G2 mice had significantly lower podocyte density than age-matched WT and Tg-G0 mice had, a difference that was not evident at weaning. Notably, a pregnancy-associated phenotype that encompassed eclampsia, preeclampsia, fetal/neonatal deaths, and small litter sizes occurred in some Tg-G0 mice and more severely in Tg-G2 mice. Similar to human placenta, placentas of Tg mice expressed APOL1. Overall, these results suggest podocyte depletion could predispose individuals with APOL1 risk genotypes to kidney disease in response to a second stressor, and add to other published evidence associating APOL1 expression with preeclampsia.
Frontal Sinusitis Causing Epidural Abscess and Puffy Tumor
Authors: Taija Kristina Nicoli, Antti Mäkitie
Journal: New England Journal of Medicine (2014)

A previously healthy 13-year-old boy presented to the otorhinolaryngology clinic with soft, well-demarcated, painless swelling of the forehead. He had no definite symptoms of sinusitis but had had a headache and fluctuating fever for 3 weeks.
BIFUNCTIONAL ANTIBODY CLINICAL TRIALS: A NEW METHOD FOR CANCER IMAGING AND THERAPY.
Authors: Dwight R. Stickney, James M. Frincke, James B. Slater, Clarence N. Ahlem, Bruce Merchant, James M. Slater, Loma Linda
Journal: Clinical Nuclear Medicine (1987)

Stickney, Dwight R.; Frincke, James M.; Slater, James B.; Ahlem, Clarence N.; Merchant, Bruce; Slater, James M.; Linda, Loma Author Information
Eating disorders: the big issue
Authors: Ulrike Schmidt, Roger Adan, Ilka Böhm, Iain C Campbell, Alexandra Dingemans, Stefan Ehrlich, Isis Elzakkers, Angela Favaro, Katrin Giel, Amy Harrison, Hubertus Himmerich, Hans W Hoek, Beate Herpertz-Dahlmann, Martien J Kas, Jochen Seitz, Paul Smeets, Lot Sternheim, Elena Tenconi, Annemarie van Elburg, Eric van Furth, Stephan Zipfel
Journal: The Lancet Psychiatry (2016)
Large gastric intramural hematoma: unusual complication of endoscopic submucosal dissection
Authors: C. Yang, H. Yen
Journal: Endoscopy (2011)

A 72-year-old woman was referred for evaluation of a gastric subepithelial tumor ([Fig. 1]). The patient had no remarkable medical history. Laboratory evaluation revealed normal platelet count and coagulation profiles. Following discussion with the patient, diagnostic endoscopic submucosal dissection (ESD) was carried out. The procedure was initiated with a submucosal saline injection using a 23-G injection needle (NM-200L-0423, Olympus, Tokyo, Japan) to raise the lesion. Soon after the injection, the patient experienced epigastric pain and the formation of a hematoma, which progressively enlarged over the injection site ([Fig. 2]). The patient was admitted and received conservative treatment including blood transfusion, fasting, a proton pump inhibitor (esomeprazole), and pain control using tramadol. Follow-up endoscopic examination on day 6 revealed an enormous ulcer in the area of the injection site ([Fig. 3]). Oral feeding was recommenced and the patient was discharged. Follow-up endoscopy after 3 months revealed complete healing of the ulcer with some scarring ([Fig. 4]).
Abstract 487: Evidence for tumor initiating stem cells in lung cancer
Authors: Wen Cai Zhang, He Yang, Boon Seng Soh, Li Li Sun, Tan Min Chin, Elaine Hsuen Lim, Bing Lim
Journal: Cancer Research (2011)

Abstract Despite advances in our knowledge of the genetics of cancer and some progress in cancer treatment over the last few decades, lung cancer remains the leading cause of cancer mortality worldwide. Therefore the identification of new therapeutic targets is necessary and important. By applying xeno-transplantation of primary cells from lung cancer specimens into immune deficient mice, we have identified a subpopulation of cells that can form tumor in transplanted mice which histologically resemble the primary tumor. This subpopulation can be enriched 200 fold for tumor initiating cells (TICs) by sorting primary tumor cells with a specific cell surface marker. The TIC population can give rise to unique epithelial colonies when seeded on feeders. Primary tumor cells when cultured serum free with EGF and FGF give rise to tumor-spheres that contain TICs at greater than 2% frequency. Microarray analysis of TICs from primary tumor samples, xenografts and tumor spheres are analyzed to derive “gene signature” of lung TICs. Several oncogenes and genes in metabolic pathways are overexpressed. Amongst them, LIN28B appears amongst the top list. Knockdown of LIN28B results in reduced tumor growth and, conversely, overexpression of LIN28B leads to transformation of NIH/3T3 and increases clonogenicity of normal lung fibroblasts. The isolation of lung TICs should facilitate further investigation of the cellular origin and carcinogenesis of lung cancers. 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 487. doi:10.1158/1538-7445.AM2011-487
miRNA determination from EUS-FNA pancreatic samples
Authors: M Gironella, G Fernández-Esparrach, O Sendino, JJ Lozano, G Ramírez, S Castellví-Bel, M Pellisé, J Llach, A Castells, A Ginès
Journal: Endoscopy (2011)

Background: miRNAs are 18–25-nucleotide single-stranded ribonucleic acids that can each repress protein synthesis of many target genes by interacting with messenger RNA transcripts. It is known that they may participate in oncogenesis. Previous investigations demonstrated that miRNAs are potential biomarkers for several types of cancer.
415 SNP rs12356193 AND PLASMA CARNITINE LEVELS ARE ASSOCIATED WITH HBsAg LOSS AFTER COMBINATION TREATMENT WITH PEGINTERFERON AND ADEFOVIR
Authors: L. Jansen, A. de Niet, E.P. van Iperen, K.A. van Dort, R.B. Takkenberg, D.J. Chin, H.L. Zaaijer, H.L.A. Janssen, N.A. Kootstra, H.W. Reesink
Journal: Journal of Hepatology (2013)
P1300 EFFICACY AND SAFETY OF DACLATASVIR IN COMBINATION WITH ASUNAPREVIR (DCV+ASV) IN CIRRHOTIC AND NON-CIRRHOTIC PATIENTS WITH HCV GENOTYPE 1B: RESULTS OF THE HALLMARK DUAL STUDY
Authors: J.-H. Kao, J. Heo, B. Yoffe, W. Sievert, I. Jacobson, F. Bessone, C.-Y. Peng, S. Roberts, K.T. Yoon, J. Kopit, M. Linaberry, S. Noviello, E. Hughes, M. Manns
Journal: Journal of Hepatology (2014)
SAPHO Syndrome Mimicking Metastases on Bone Scintigraphy
Authors: P. D. ROBINS, MARTIN P. BLAKE, P. S. ROBINSON
Journal: Clinical Nuclear Medicine (1998)

SAPHO syndrome is an acronym for a cluster of clinical manifestations including synovitis, acne, palmoplantar pustulosis, hyperostosis, and osteitis. The pathogenesis is unknown. It has a propensity for the anterior chest wall, characterized by sclerosis, hyperostosis, and arthritis of the sternoclavicular joints and costochondral junctions. It may also affect the spine and sacroiliac joints. Long bone involvement may mimic malignancy or infection radiologically. A case is presented with features suggestive of metastatic disease. The combination of sternoclavicular and appendicular involvement provided clues to the diagnosis on bone scintigraphy. Awareness of this unusual syndrome is necessary to avoid misdiagnosis.
A Neutrophil Disorder Induced by Capnocytophaga, a Dental Micro-Organism
Authors: Susan B. Shurin, Sigmund S. Socransky, Edward Sweeney, Thomas P. Stossel
Journal: New England Journal of Medicine (1979)

We recovered capnocytophaga, a gram-negative anaerobe implicated in the pathogenesis of periodontal disease, from two patients with a history of dental infections. Neutrophils from both patients failed to acquire the asymmetric shape characteristic of normal neutrophils. Fluorescein staining of the patients' living neutrophils remained diffuse and patchy instead of showing the normal pattern in which the fluorescence is swept into the rear of the cell. The locomotion of one patient's neutrophils in vitro was less than 50 per cent of that of normal neutrophils, and migration of this patient's neutrophils into dermal abrasions was reduced, although phagocytosis and nitroblue tetrazolium reduction were normal. All abnormalities of neutrophil morphology and function disappeared after eradication of the capnocytophaga infections. Sonicates and culture medium of capnocytophaga contained a dialyzable substance that caused normal neutrophils to behave like neutrophils obtained from the infected patients.
Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves
Authors: Raj R. Makkar, Gregory Fontana, Hasan Jilaihawi, Tarun Chakravarty, Klaus F. Kofoed, Ole De Backer, Federico M. Asch, Carlos E. Ruiz, Niels T. Olsen, Alfredo Trento, John Friedman, Daniel Berman, Wen Cheng, Mohammad Kashif, Vladimir Jelnin, Chad A. Kliger, Hongfei Guo, Augusto D. Pichard, Neil J. Weissman, Samir Kapadia, Eric Manasse, Deepak L. Bhatt, Martin B. Leon, Lars Søndergaard
Journal: New England Journal of Medicine (2015)

A finding of reduced aortic-valve leaflet motion was noted on computed tomography (CT) in a patient who had a stroke after transcatheter aortic-valve replacement (TAVR) during an ongoing clinical trial. This finding raised a concern about possible subclinical leaflet thrombosis and prompted further investigation.We analyzed data obtained from 55 patients in a clinical trial of TAVR and from two single-center registries that included 132 patients who were undergoing either TAVR or surgical aortic-valve bioprosthesis implantation. We obtained four-dimensional, volume-rendered CT scans along with data on anticoagulation and clinical outcomes (including strokes and transient ischemic attacks [TIAs]).Reduced leaflet motion was noted on CT in 22 of 55 patients (40%) in the clinical trial and in 17 of 132 patients (13%) in the two registries. Reduced leaflet motion was detected among patients with multiple bioprosthesis types, including transcatheter and surgical bioprostheses. Therapeutic anticoagulation with warfarin, as compared with dual antiplatelet therapy, was associated with a decreased incidence of reduced leaflet motion (0% and 55%, respectively, P=0.01 in the clinical trial; and 0% and 29%, respectively, P=0.04 in the pooled registries). In patients who were reevaluated with follow-up CT, restoration of leaflet motion was noted in all 11 patients who were receiving anticoagulation and in 1 of 10 patients who were not receiving anticoagulation (P<0.001). There was no significant difference in the incidence of stroke or TIA between patients with reduced leaflet motion and those with normal leaflet motion in the clinical trial (2 of 22 patients and 0 of 33 patients, respectively; P=0.16), although in the pooled registries, a significant difference was detected (3 of 17 patients and 1 of 115 patients, respectively; P=0.007).Reduced aortic-valve leaflet motion was shown in patients with bioprosthetic aortic valves. The condition resolved with therapeutic anticoagulation. The effect of this finding on clinical outcomes including stroke needs further investigation. (Funded by St. Jude Medical and Cedars-Sinai Heart Institute; Portico-IDE ClinicalTrials.gov number, NCT02000115; SAVORY registry, NCT02426307; and RESOLVE registry, NCT02318342.).
Abstract 3081: Crosstalk between Runx2 regulatory network and PI3K/Akt signaling pathway in breast cancer cells
Authors: Manish Tandon, Zujian Chen, Jitesh Pratap
Journal: Cancer Research (2012)

Abstract The Runt-related transcription factor Runx2 is essential for skeletal development but is also aberrantly expressed in several cancers (e.g., breast, prostate and osteosarcoma) where it promotes cell migration, invasive and growth properties of cancer cells. The phosphatidylinositol 3′ kinase (PI3K)/Akt signaling pathway is linked to Runx2-dependent skeletogenesis, however, the mechanisms of Runx2 role in PI3K-Akt signaling in breast cancers, and its implication in cancer progression remains under investigated. To mechanistically determine the function of Runx2 in epidermal growth factor (EGF)-induced PI3K/Akt signaling and concomitantly ensuing downstream signaling events, we modulated Runx2 expression levels in immortalized normal MCF-10A and invasive MDA-MB-231 cells via lentiviral vector-mediated gene delivery. The Runx2 over-expression in EGF-stimulated MCF-10A cells increased the cellular response towards PI3K inhibitor LY294002 as indicated by a decline in Akt (Serine 473) phosphorylation (pAkt) levels. This effect could be restored by Runx2 suppression indicating the specificity of Runx2 function in Akt regulation. In MDA-MB-231 cells, Runx2 over-expression and, surprisingly, suppression profoundly inhibited pAkt suggesting that a threshold level of Runx2 is required for phosphorylation of Akt. The Runx2-mediated decline in pAkt was completely reversed by the Runx2-DNA binding mutant over-expression indicating that Runx2 DNA binding domain is essential for Akt inhibition. To further dissect the mechanism of Runx2-mediated regulation of pAkt levels in MDA-MB-231 cells, we examined the protein levels of phosphatases and kinases associated with PI3K/Akt signaling pathway. These analyses revealed that PH domain and leucine rich repeat protein phosphatase 1 (PHLPP1) levels were directly responsive to Runx2. Chromatin immunoprecipitation studies showed Runx2 recruitment on the proximal promoter of PHLPP1 suggesting that Runx2 mediates its effect on Akt activity, in part by regulating PHLPP1 expression. Furthermore, Runx2 overexpression increased nuclear translocation of a forkhead box transcription factor FoxO1, a downstream molecule of PI3K/Akt signaling indicating an indirect Runx2 affect on FoxO1 transcriptional activity in MDA-MB-231 cells as examined by western blot analysis and immunofluorescence studies. Together, our results identified clinically relevant and novel mechanisms of Runx2 regulatory network in PI3K/Akt signaling pathway that could have important consequences in targeting breast cancer-associated cell survival and invasive properties. 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 3081. doi:1538-7445.AM2012-3081
Efficacy of Gene Therapy for a Prototypical Lysosomal Storage Disease (GSD-II) Is Critically Dependent on Vector Dose, Transgene Promoter, and the Tissues Targeted for Vector Transduction
Authors: Enyu Ding, Huimin Hu, Bradley L. Hodges, Felicia Migone, Delila Serra, Fang Xu, Yuan-Tsong Chen, Andrea Amalfitano
Journal: Molecular Therapy (2002)

Lysosomal storage diseases are an intriguing target for gene therapy approaches, as transduction of a "depot" organ with a transgene encoding a lysosomal enzyme can be followed by secretion, systemic distribution, downstream uptake, and lysosomal targeting of the enzyme into non-transduced tissues. These benefits are of utmost importance when considering gene therapy approaches for glycogen storage disease type-II (GSD-II). GSD-II is a prototypical lysosomal storage disorder caused by lack of intralysosomal acid α-glucosidase (GAA) activity. Lack of GAA can result in a proximal limb myopathy and respiratory and cardiac failure, each due to abnormal glycogen accumulation in the skeletal muscles or cardiac tissues, respectively. After converting the liver into a "depot" organ, we found that intravenous injection of the [E1-,polymerase-]AdGAA vector allowed for hepatic secretion of GAA over an at least 20-fold dosage range. We noted that very low plasma GAA levels (derived from hepatic secretion of GAA) can allow for GAA uptake by muscle tissues (skeletal or cardiac), but significantly higher plasma GAA levels are required before glycogen "cross-correction" can occur in these same tissues. We also demonstrated that liver-specific enhancer/promoters prolonged GAA transgene expression from persistent [E1-,polymerase-] adenovirus based vector genomes for at least 180 days, and significantly diminished the amounts of neutralizing anti-GAA antibodies elicited in this animal model. Finally, we demonstrated that skeletal muscles can also serve as a "depot" organ for GAA secretion, allowing for secretion of GAA and its uptake by noninfected distal tissues, although glycogen reductions in non-injected muscles were not achieved by the latter approach.
Treatment of Chronic Stable Angina
Authors: Marvin L. Murphy, Herbert N. Hultgren, Katherine Detre, James Thomsen, Timothy Takaro
Journal: New England Journal of Medicine (1977)

We evaluated the effect of saphenous-vein-bypass grafting on survival in patients with chronic stable angina by comparing medical and surgical treatment in a large-scale, prospective randomized study. Excluding patients with left-main-coronary-artery disease who have already been reported, a total of 596 patients were entered into this study; when randomized into a medical group (310 patients) and a surgical group (286 patients), entry clinical and angiographic base lines were comparable. Operative mortality at 30 days was 5.6 per cent. At an average of one year after operation, 69 per cent of all grafts were patent, and 88 per cent of the surgical patients had atleast one patent graft. There was no statistically significant difference in survival, at a minimal follow-up interval of 21 months, between patients treated medically and those treated with saphenous-vein-bypass grafting. At 36 months, 87 per cent of the medical group and 88 per cent of the surgical group were alive.
PTU-268 Day-case loop ileostomy closure: feasible, safe and efficient
Authors: A Bhalla, O Peacock, J Williams, S Tou, N Hurst, W Speake, G Tierney, J Lund
Journal: Gut (2015)

<h3>Introduction</h3> Over 5,000 loop ileostomy closures were performed within the United Kingdom in 2013 with a median inpatient stay of 5 days. Previously we have successfully implemented a 23-hour protocol for loop ileostomy closure which was modified to create one specific for same-day discharge. We present our early experience of day-case loop ileostomy closure. <h3>Method</h3> A specific patient pathway for day-case discharge following loop ileostomy closure was implemented at a single UK institution. Inclusion criteria conform to British Association of Day Surgery guidelines. Exclusion criteria include post-operative chemo-radiotherapy, multiple co-morbidities and social care needs. Follow-up consisted of telephone contact (24 and 72 h post-discharge) and a routine outpatient appointment. Patients were provided with a 24 h contact point in case of emergency. <h3>Results</h3> Fifteen patients were enrolled (12 males; median age 67 years (39–80); median operating time 41 min (23–80)). Thirteen patients had ileostomy formation during low anterior resection for adenocarcinoma, one patient had an ileostomy fashioned during reversal of Hartman’s procedure and one for a function bowel disorder. Median time from primary procedure to day-case loop ileostomy closure was 8 months (3–14 months). Every patient was discharged on the day of surgery. There were no complications related to surgery, and one readmission with urinary tract infection. Median length of follow-up was 4 months (2–16 months). <h3>Conclusion</h3> Our early experience shows day-case loop ileostomy closure is feasible, safe and efficient. This protocol will become standard within our institution for suitable patients, saving on average 5 inpatient bed days per patient. <h3>Disclosure of interest</h3> None Declared.