tbuckley/cabot-search huggingface dataset:
Abstract 5253: SOX2-mediated cell survival and chemoresistance in lung cancer.
Authors: Yu-Ting Chou, Chih-Chan Lee, Shih-Hsin Hsiao, Sey-En Lin, Sheng-Chieh Lin, Yuan-Hung Wang, Cheng-Wen Wu
Journal: Cancer Research (2013)

Abstract Tumor cells have long been observed to share several biological characteristics with normal stem/progenitor cells; however, the oncogenic mechanisms underlying the stemness features remain elusive. Here we report the involvement of BCL2L1 in SOX2-mediated cell survival and chemoresistance in lung cancer. SOX2 was associated with poor prognosis in lung cancer patients and was expressed in a subclass of lung cancer cells the survival and chemoresistance of which were dependent on SOX2 stem cell signaling. SOX2 promoted chemoresistance, and silencing of SOX2 perturbed mitochondrial function, causing marked apoptosis and autophagy. Moreover, SOX2 knockdown attenuated tumor growth in a xenograft mouse model. SOX2 induced BCL2L1 expression, the ectopic expression of which rescued the effects of SOX2 silencing on apoptosis, autophagy, and mitochondrial function. SOX2 and BCL2L1 expression levels were significantly correlated in human lung tumors, supporting the involvement of BCL2L1 in SOX2-mediated oncogenesis. Our findings reveal for the first time that SOX2-BCL2L1 signaling maintains mitochondrial integrity and enhances cell survival, leading to increased chemoresistance in lung cancer cells. Citation Format: Yu-Ting Chou, Chih-Chan Lee, Shih-Hsin Hsiao, Sey-En Lin, Sheng-Chieh Lin, Yuan-Hung Wang, Cheng-Wen Wu. SOX2-mediated cell survival and chemoresistance in lung cancer. [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 5253. doi:10.1158/1538-7445.AM2013-5253
Abstract 3990: SPANXA1 suppresses tumor metastasis through WNT pathway in lung cancer
Authors: Po-Hsiang Kang, Chia-Ying Hsu, Kang-Yi Su, Hsuan-Yu Chen, Sung-Liang Yu
Journal: Cancer Research (2012)

Abstract SPANX (Sperm protein associated with the nucleus, X-linked) gene family has been found higher expression in many cancers, such as testicular germ tumor, melanoma, glioblastoma and hematologic malignancies. However, in our previous study, the gene expression array analysis showed that the expression of SPANX family member A1 (SPANXA1) was higher in lower invasive lung cancer cells, CL 1-0, than in higher invasive cells, CL 1-5. Real-time PCR was used to confirm that mRNA expression of SPANXA1 was 8 times higher in CL 1-0 than CL 1-5. In vitro assays showed that migration and invasion abilities of CL 1-5 stable transfectants were decreased in a dose-depended manner. Interestingly, cell morphology dramatically changed from mesenchymal-like to epithelial-like in CL 1-5 SPANXA1 stable transfectants, which was consistent to its decreased invasive ability in vitro. Therefore, we demonstrated metastasis ability of CL 1-5 SPANXA1 stable transfectants would be down-regulated in vivo, which was performed in mouse metastasis model by tail-vein injection. Next, we set up CL 1-0 lentiviral-base shRNA knockdown clones, and the cell mobility and invasion ability were increased. Because SPANXA1 could induce the cell morphology change, we evaluate the effect of SPANXA1 on the expression of EMT markers. We found up-regulation of E-cadherin, an epithelial marker, and down-regulation of vimentin and N-cadherin, which were known as mesenchymal markers in presence of SPANXA1. Finally, to identify the underlying mechanism of SPANXA1, we carried out gene expression array and 3 of top 10 pathways are EMT-related. Furthermore, quantitative RT-PCR validation showed WNT pathway is involved in SPANXA1-repressed metastasis indicated that SPANXA1 might provide a new treatment in lung cancer. 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 3990. doi:1538-7445.AM2012-3990
Abstract 474: Complete regression and long-term specific protective immune responses obtained in rodent tumor models after intratumoral treatment with LTX-315 .
Authors: Øystein Rekdal, Gunnar Kvalheim, Pål-Dag Line, Bent Rolstad, Ketil Camilio, Gerd Berge, Janne Nestvold, Mengyu Wang, Jihua Shi, Ali Areffard, Baldur Sveinbjørnsson
Journal: Cancer Research (2013)

Abstract LTX-315 is a de novo designed peptide derived from a naturally occurring host defence peptide. LTX-315 has the potential to induce long-term specific protective immune responses by stimulating immune cells, inducing tumor cell lysis with subsequent release of danger signals (e.g. HMGB1) and tumor associated antigens (TAA`s). A complete tumor regression has been obtained in several syngenic rodent tumor models by intratumoral (i.t.) injection with LTX-315. The effect was T- cell- dependent since the intervention was inefficient in immune-deficient animals. Studies on treated tumor tissue confirmed infiltration of immune cells and a switch in the cytokine profile towards a Th1 response. Successfully treated animals were protected against re-challenge with the tumor cell type treated, but not against other types of tumor cells. Moreover, tumor resistance could be adoptively transferred by spleen cells from LTX-315-treated animals. The resistance was abrogated by depletion of T- lymphocytes. Additional studies also indicate that LTX-315`s potential to locally activate the innate immune system by the immunogenic stressing of cells, in addition to the subsequent release of endogenous adjuvants and natural danger signals, provides a strong rationale for using LTX-315 as an adjuvant for vaccines based on tumor-associated antigens (TAA) and for combination with other types of immune–modulatory therapies. LTX-315 is currently being tested in a Phase I dose escalation clinical study and may represents a novel strategy for personalized in situ vaccination against cancer. Citation Format: Øystein Rekdal, Gunnar Kvalheim, Pål-Dag Line, Bent Rolstad, Ketil Camilio, Gerd Berge, Janne Nestvold, Mengyu Wang, Jihua Shi, Ali Areffard, Baldur Sveinbjørnsson. Complete regression and long-term specific protective immune responses obtained in rodent tumor models after intratumoral treatment with LTX-315 . [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 474. doi:10.1158/1538-7445.AM2013-474
Urinary Excretion of the Serotonin Metabolite, 5-Hydroxyindoleacetic Acid, in Various Clinical Conditions
Authors: Bernard J. Haverbagk, Albert Sjoerdsma, Luther L. Terry
Journal: New England Journal of Medicine (1956)

CONSIDERABLE interest is being given to the possible role of serotonin (5-hydroxytryptamine) in various physiologic and pathologic processes. This amine is found primarily in the gastrointestinal tract, blood platelets and brain of mammalian species.1 2 3 4 Although the physiologic role of serotonin is unknown, it is a potent stimulant of smooth muscle in the gastrointestinal tract, bronchi and blood vessels.5 , 6 The point has been raised that it may be involved in the maintenance of normal intestinal motility7 and in hemostasis.8 9 10 The amine has also been considered a hormone regulating the circulation and function of the kidney.5 On the basis of the observation . . .
Alternative approach to pericardial effusion: EUS guided transesophageal pericardiocentesis
Authors: Hashimoto Yusuke, Maruoka Naotaka, Nagahama Masaa
Journal: Endoscopy (2011)

Introduction: Echocardiographic-guided pericardiocentesis is the preferred initial procedure for the diagnosis and treatment of pericardial effusion. Pericardial effusion is rarely located in the posterior side of pericardial sac, which makes it difficult for cardiologist to perform Echocardiographic-guided pericardiocentesis through the subxiphoid route. EUS guided-transesophageal pericardiocentesis can be an alternative method when the approach to the pericardial effusion is anatomically closer to esophagus than to subxiphoid.
AB0704 Impact of Lumbar Syndesmophyte on Bone Heath as Assessed by Bone Density (BMD) and Bone Texture (TBS) in Men with Axial Spondyloarthritis
Authors: L. Wildberger, V. Boiadjieva, D. Hans, N. Stoilov, M. Ivanova, R. Stoilov, R. Rashkov, B. Aubry-Rozier
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patients with spondyloarthritis (AS) have an elevated incidence of osteoporosis and are at increased risk of pathological vertebral fracture. Evaluation of bone by dual energy X-Ray absorptiometry (DXA) has its limits in fracture prediction, already known in this population, probably because it only measures quantity, but not quality of bone. One hypothesis is that the presence of lumbar syndesmophyte could overestimate the spine BMD. Trabecular bone score (TBS) is a new texture measurement correlated with bone microarchitecture. Previous studies have shown that TBS is not impacted by osteoarthritis and thus could be a predictor of fracture better than spine BMD. <h3>Objectives</h3> We aimed to evaluate a male population of AS with BMD and TBS measurement and see the impact of lumbar syndesmophyte <h3>Methods</h3> Two cohorts of AS male patients (Lausanne, Sofia) with AS disease, clinical and bone parameters (femoral neck and total spine BMD + spine TBS) were merged. We compared BMD and TBS results regarding to the presence/absence of syndesmophyte and compared to young normative values (T-score for both BMD and TBS). T-tests were used to compare the two groups. <h3>Results</h3> Our study concerned 22 men (10 men with lumbar syndesmophytes (L1 to L4, ≥1), 11 without), all fulfilled the ASAS criteria, no difference in age (47 years old) and BMI. Mean spine BMD T-score were 0.098±2.11 and -1.17±0.73 (p&lt;0.05) respectively for AS men with and without syndesmophytes, 0±2.39 and -1.6±0.9 (p&lt;0.05) if vertebrae with osteoarthritis were excluded. Mean femoral neck BMD T-score was -1.95±0.83 and -0.82±071 (p&lt;0.05) respectively for AS men with and without syndesmophytes. Mean TBS was 1.269±0.081 and 1.338±0.083 (p&lt;0.05) and corresponding T-score TBS were -1.395±0.885 and -0.640±0.907 (p&lt;0.05) respectively for AS men with and without syndesmophytes. <h3>Conclusions</h3> The two populations (Lausanne and Sofia) had comparable BMD and TBS results, after exclusion of degenerative vertebrae and adjustment for the two DXA machines. As expected, the only "normal" result was spine BMD in AS men with syndesmophytes. Others results were lower than in a normal population. Interestingly, even if men with syndesmophyte had normal spine BMD results, they had lower TBS results than men without syndesmophyte and lower femoral neck BMD. All results are statistically significant. These results have to be confirmed in term of disease activity and fracture risk. In conclusion, spine BMD is erroneously influenced by syndesmophyte unlike spine TBS and femoral BMD. We can recommend to evaluate bone health in AS male population with syndesmophyte by measurement of spine TBS and femoral BMD. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4219
A memorable patient: All in the family
Authors: E M M Besterman
Journal: BMJ (1999)

In the early 1950s I was a registrar at the special unit for juvenile rheumatism, a part of the Canadian Red Cross Memorial Hospital, Taplow, Buckinghamshire. This general hospital also housed adult cardiac patients. In those more leisurely days a morning coffee break was customary to discuss patients, research, and other projects. On one such break I presented my chief, Paul Wood, who was then the eminent British cardiologist, with an electrocardiogram for his opinion. After a quick glance he said “a classical inferior infarct, what’s the problem?” I replied that the problem was that the patient happened to be a 10 year old girl with rheumatic fever. Wood blanched, threw his coffee at me, and changed the subject.

Some years later I was telephoned at the Institute of Cardiology by my opposite number at the Hammersmith Hospital to ask if I remembered this girl. He told me that her brother had just been diagnosed as suffering from the newly described asymmetrical hypertrophy of the heart and he was investigating the family for any familial trend and found my former patient. This condition had recently been recognised from necropsy studies by Donald Teare.1 Clinical recognition was in its early stages and my girl’s electrocardiogram changes were typical of the pathology, now better known as hypertrophic obstructive cardiomyopathy or HOCM, which has a strong familial prevalence.
American Mock World Health Organization (AMWHO): introducing students to global health policy through a model WHO conference
Authors: Edith Lee, Mia Lei, Emma Holcomb
Journal: The Lancet Global Health (2016)

Background The American Mock World Health Organization (AMWHO) was established in 2013, and between October 2-4, 2015, the second AMWHO conference convened at the University of North Carolina, Chapel Hill, NC, USA. The aim of AMWHO is to engage students in health policy, empower future global leaders through simulations of WHO meetings, allow students to practise their knowledge of global health, and sharpen their skills in diplomacy, communication, problem solving, and conflict resolution. Here, we describe the AMWHO and report outcomes for delegates at the 2015 conference.
THE BURDEN AND IMPACT OF SUSTAINED VENTRICULAR ARRHYTHMIAS AFTER CONTINUOUS-FLOW LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION
Authors: Sing-Chien Yap, Rahat Muslem, Faiz Ramjankhan, Nicolaas De Jonge, Alina A. Constantinescu, Olivier C. Manintveld, Tamas Szili-Torok, Kadir Caliskan
Journal: Journal of the American College of Cardiology (2016)
The Pharmacologic Treatment of Depression
Authors: John A. Oates, Alastair J.J. Wood, William Z. Potter, Matthew V. Rudorfer, Husseini Manji
Journal: New England Journal of Medicine (1991)

IN the past 30 years, there have been major changes in the diagnosis and treatment of depression. Moreover, the biochemical theories of depression suggest that subgroups of patients respond to drugs that affect particular neurotransmitters, in a manner analogous to suggested subgroup responses in hypertension.1 Nonetheless, the original tricyclic antidepressant agents are still the drugs of choice for most patients with major depressive disorders.2 , 3 What follows is a review directed to creating a rational basis for selection among the available antidepressant drugs.Diagnosis of DepressionDepression is currently diagnosed according to the 1987 revision of the Diagnostic and Statistical Manual . . .
Abstract 3095: Oncogenic miRNA-182-5p targets Smad4 and RECK in human bladder cancer.
Authors: Hiroshi Hirata, Koji Ueno, Varahram Shahryari, Yuichiro Tanaka, Z. Laura Tabatabai, Yuji Hinoda, Rajvir Dahiya
Journal: Cancer Research (2013)

Abstract Abstract Introduction and Objective: Onco-miR-182-5p has been reported to be over-expressed in bladder cancer (BC) tissues however a detailed functional analysis of miR-182-5p has not been carried out in BC. Therefore the purpose of this study was to: 1. conduct a functional analysis of miR-182-5p in bladder cancer, 2. assess its usefulness as a tumor marker, 3. identify miR-182-5p target genes in BC. Methods: Initially we found that miR-182-5p expression was significantly higher in bladder cancer compared to normal tissues and high miR-182-5p expression was associated with shorter overall survival in BC patients. To study the functional significance of miR-182-5p, we over-expressed miR-182-5p with miR-182-5p precursor. Results: Cell proliferation, migration and invasion abilities were increased in BC cells. However cell apoptosis was inhibited by miR-182-5p. We also identified Smad4 and RECK as potential target genes of miR-182-5p using several algorithms. 3’UTR luciferase activity of these target genes was significantly decreased and protein expression of these target genes was significantly up-regulated in miR-182-5p inhibitor transfected bladder cancer cells. MiR-182-5p also increased nuclear beta-catenin expression and while Smad4 repressed nuclear beta-catenin expression. Conclusions: Our data suggests that miR-182-5p plays an important role as an oncogene by knocking down RECK and Smad4, resulting in activation of the Wnt-beta-catenin signaling pathway in bladder cancer. Source of Funding: Grants RO1CA138642, RO1CA130860, RO1CA160079, VA Research Enhancement Award Program (REAP) and Merit Review grants Citation Format: Hiroshi Hirata, Koji Ueno, Varahram Shahryari, Yuichiro Tanaka, Z. Laura Tabatabai, Yuji Hinoda, Rajvir Dahiya. Oncogenic miRNA-182-5p targets Smad4 and RECK in human bladder cancer. [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 3095. doi:10.1158/1538-7445.AM2013-3095
CLINICAL OUTCOMES OF RETRIEVABLE INFERIOR VENA CAVA FILTER PLUS ANTICOAGULATION VERSUS ANTICOAGULATION ALONE ON HIGH-RISK PATIENTS: A META-ANALYSIS
Authors: Daniel Garcia, Mohammad Ansari, Rhanderson Cardoso, Cesar Mendoza-Trauco, Larry Diaz-Sandoval, Fadi Saab, Jihad Mustapha
Journal: Journal of the American College of Cardiology (2016)
SAT0203 A Novel Mri-Based Analysis Workflow for Spinal Lesions in Ankylosing Spondylitis
Authors: D. Roettger, J. Vicente, M. Hinton, O. Kubassova, P. Taylor
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Advances in novel MRI techniques are promising for assessing progression of Ankylosing Spondylitis and effectiveness of treatment. Nevertheless, MRI is not widely utilized in clinical setting due to the lack of a fast, reproducible scoring system. A scoring method has been developed for the quantification of spinal lesions that is fast to process and reduces inter and intra observer variability and requires rough regions of interest (ROI). This method is built as a module of Dynamika, an image analysis diagnostic platform. <h3>Objectives</h3> To provide a reproducible scoring method for the quantification of spinal lesions from static MRI scans. <h3>Methods</h3> Baseline and follow-up cervical, thoracic and lumbar MRI scan series from 36 patients (216 scans in total) were processed by 3 different readers. The followed workflow for each reading was: 1) Draw spine outlining ROIs in sagittal views; 3) Compute a Norml parametric map [1] by using the middle slice ROI as a baseline; 4) Adjust MRI histogram centre and width to 1 and 2 respectively; 5) Group the 2D ROIs into a volume of interest (VOI); 6) Record the sum of all positive pixel values in the VOI (SumNormI). The windowing of the MRI histogram is defined with the aim of quantifying the spine while excluding discs. Pearson9s Coefficient was calculated to assess the inter-observer variance. The coefficient was calculated for the SumNormI obtained for each VOI and for the normalized SumNormI (SumNormI divided by the number of slices comprising the VOI). After a week, readers were asked to repeat the analysis for 48 scans in order to measure the intra-observer variance with the Lin9s Concordance Correlation Coefficient [2]. <h3>Results</h3> By adjusting the window as described, NormI focuses on intensities between healthy spine and discs, assuming lesion have intensities between both (see Figure). Reproducibility was assessed in terms of inter and intra-observer variance (see Table). Pearson9s Coefficient was significantly high for each pair of readers (p&lt;0.005), which suggests that the proposed workflow is robust for different readers. Intra-observer reliability also achieved high values (p&lt;0.005) when comparing the results recorded after a second reading. <h3>Conclusions</h3> The presented workflow provides a method for scoring of spinal lesions from static MRI scans. This workflow is reproducible and only requires the drawing of rough ROIs. <h3>References</h3> O. Kubassova et al. A novel diagnostic platform for quantifying Ankylosing Spondylitis and general Spondylitis from MRI, in Proceedings of 99th Annual Meeting RSNA, December 1 – 6, 2013 Biometrics Vol. 45, No. 1, Mar., 1989 <h3>Acknowledgements</h3> We acknowledge Jener Basilio for his guidance and cooperation in the assessment of the reproducibility of this workflow. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5651
Abstract 3309: Blocking the Notch pathway inhibits the epithelial-mesenchymal transition (EMT) status in lung cancer and alters chemoresistance
Authors: Khaled A. Hassan, Luo Wang, Paige O'Dowd, Gwangil Kim, Hasan Korkaya, April Davis, Suling Liu, Gregory P. Kalemkerian, Max Wicha
Journal: Cancer Research (2012)

Abstract Background: The Epithelial-Mesenchymal Transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. EMT cells have stem cells properties and possess the characteristics of cell motility, invasiveness and chemotherapy resistance. EMT expression profile correlates with poor outcome in multiple tumors and there is evidence suggesting an integral role of Notch pathway in mediating EMT. In this study, we investigated Notch activity and EMT status and the correlation with chemoressitance in non-small cell lung cancer (NSCLC). Results: Transduction of multiple NSCLC cell lines, NCI-H1299, NCI-H460, NCI-H358, NCI-H441 with a Notch GFP-reporter construct identified a subset of cells with high Notch activity (GFP-pos). We compared the tumor invasivness capacity of GFP-pos and GFP-neg cells utilizing a transwell invasion assay. Cells with high Notch activity, as evidenced by GFP expression, had multiple fold higher invasion capability compared to GFP-neg cells (p=0.0001). To evaluate whether Notch activity correlates with resistance to chemotherapy, we treated GFP-pos and GFP-neg cells with docetaxel or cisplatin and assessed Annexin V expression using flow cytometry. GFP-pos cells had five fold less apoptotic cells as compared to GFP-neg cells indicating resistance of GFP-pos cells to chemotherapy. When GFP-pos cells were exposed to a Notch signaling inhibitor inhibitor, gamma secretase inhibitor (GSI), these cells were rendered sensitive to cisplatin and docetaxel. RNA microarray analysis and RT-PCR analysis revealed an increased expression of EMT related genes (Vimentin, N-Cadherin, Snail-1,….) in GFP-pos cells as compared to GFP-neg cells. Furthermore, NOD/SCID mice with subcutaneous lung tumor xenografts treated with GSI showed decreased expression of downstream effectors of Notch as well as vimentin. This combination of GSI and docetaxel reduced tumor grwoth in mouse xenographs compared to GSI and docetaxel as single agents. Conclusion: These studies suggest that the Notch pathway is an important regulator of EMT status and that its inhibition may alter EMT chemo-resistance properties. The addition of a Notch inhibitor may enhance the efficacy of chemotherapy in the treatment of NSCLC. 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 3309. doi:1538-7445.AM2012-3309
341 CORTICOSTEROIDS AFFECT HEPATITIS C INFECTION BY MODULATING PLASMACYTOID DENDRITIC CELL FUNCTION
Authors: J. Kwekkeboom, P.E. de Ruiter, P.P.C. Boor, Q. Pan, J. de Jonge, H.J. Metselaar, H.W. Tilanus, L.J.W. van der Laan
Journal: Journal of Hepatology (2013)