tbuckley/cabot-search huggingface dataset:
PTH-074 Small bowel capsule endoscopy in the investigation of iron deficiency anaemia: referral patterns and clinical outcomes
Authors: A Koulaouzidis, S Douglas, H Naismith, J Plevris
Journal: Gut (2010)

<h3>Introduction</h3> Small Bowel capsule endoscopy (SBCE) is a useful diagnostic modality in the investigation of patients with Obscure Gastrointestinal bleed (OGIB)/Iron deficiency anaemia (IDA) when prior bi-directional endoscopies are negative. <h3>Methods</h3> We retrospectively analysed data from patients referred to our tertiary centre for investigation of unexplained IDA, after negative bidirectional endoscopies. We aimed to establish referral patterns and clinical outcomes following SBCE. <h3>Results</h3> Over a 5-year period (2004–2009), 133 patients (51 males, 82 females/mean age: 59.7) with unexplained IDA were referred to our service. Of those, 18 were referred from District General Hospitals (DGH) of South East Scotland, 106 from the Medical/Surgical Gastrointestinal (GI) service of our centre, 8 from the regional Haemophilia/Coagulation Medicine Centre (HCMC) and 1 from Renal medicine. One hundred and thirteen (n: 113/84.9%) patients were ≥40 years of age; in this group, small bowel angioectasias was the prevailing diagnosis (33/113, 29.2%), followed by Crohn9s (9/113, 7.9%), while portal hypertension GAVE/PHG (9/113, 7.9%) and undiagnosed caecal angiodysplasias (5/113, 4.42%) formed an appreciable group (12.3%). One case of coeliac and one of lymphoma were also diagnosed, together with three cases of NSAID9s-related enteropathy. SBCE was normal in 58 cases (51.3%). In the group of those &lt;40 (n: 17), 10 had normal SBCE (58.2%), 2 had Crohn9s (11.7%), 2 small bowel angioectasias (11.7%), while 1 case of Meckel9s diverticulum and 1 case of capsule retention was seen. No small bowel malignancies were diagnosed in this group. Interestingly, the percentage of normal investigations was around 50%, irrespective of the source of referral (DGH 50%, HCMC 50%, and GI 51%). Small bowel angioectasias was the prevailing pathology irrespective of referral source (DGH 22%, HCMC 25%, GI 30.2%). <h3>Conclusion</h3> In our cohort (patients with prior negative bidirectional tests), small bowel angioectasias are the prevailing cause of unexplained IDA irrespective of referral source. The referral source does not seem to impact on the percentage of normal SBCE. A significant proportion of those ≥40 years (12.3%), had pathologies missed by endoscopies. We recommend repeating bi-directional endoscopies in this age group, while on the waiting list for SBCE.
Abstract 3052: NAMPT inhibition induces mitochondrial dysfunction leading to apoptosis in chronic lymphocytic leukemia cells
Authors: Eric DJ Bouchard, Edgard M. Mejia, Iris Gehrke, Armando G. Poeppl, Donna Hewitt, James B. Johnston, Spencer B. Gibson, Grant M. Hatch, Versha Banerji
Journal: Cancer Research (2015)

Abstract We have previously shown that the NAD depletion following inhibition of NAMPT by the NA-mimetic FK866 leads to loss of mitochondrial membrane potential, depletion of cellular ATP, cytochrome C release and caspase activation in primary Chronic Lymphocytic Leukemia (CLL) cells in vitro, and that these events are coupled with an increased production of reactive oxygen species uncharacteristic of metabolic inhibition. In the present study we characterize the effect of NAD depletion on CLL mitochondria and the downstream mechanism of cell death. We profiled the mitochondrial respiration of CLL cells and control B-lymphocytes, by extracellular flux analysis, over the 48 hours following FK866 treatment and found time-dependant inhibition of respiratory capacity consistent with disruption of the electron transport chain (ETC) in CLL cells. This led to suppression of basal respiration concomitant with the rise in ROS and approximately one day before loss of cellular viability. Interestingly, Zap70-positive CLL cells exhibited increased mitochondrial respiration and respiratory capacity over Zap70-negative CLL cells, but responded similarly to NAMPT inhibition. Additionally, mitochondrial respiration was not effected by NAMPT inhibition in control B-lymphocytes. Increase autophagic flux, caspase-dependant apoptosis and mitochondrio-nuclear translocation of Apoptosis Inducing Factor (AIF) were detected by western blot. However, neither pan-caspase inhibition with Z-VAD-fmk nor inhibition of autophagy with 3-methyladenine were sufficient to prevent FK866-induced CLL cell death. We conclude that NAD depletion following inhibition of NAMPT leads to disruption of the mitochondrial ETC in CLL cells, leading to mitochondrial initiation of the intrinsic apoptosis pathway. As healthy B-lymphocytes are resistant to this NAD depletion, these downstream effects are also selective for malignant cells. We are currently working to characterize the roles of NAD and Zap70 in the regulation and function of the CLL ETC. This will not only lead to an improved understanding of CLL metabolism, but will also inform new therapeutic strategies that will effectively employ NAMPT inhibition to treat this yet-incurable disease. Citation Format: Eric DJ Bouchard, Edgard M. Mejia, Iris Gehrke, Armando G. Poeppl, Donna Hewitt, James B. Johnston, Spencer B. Gibson, Grant M. Hatch, Versha Banerji. NAMPT inhibition induces mitochondrial dysfunction leading to apoptosis in chronic lymphocytic leukemia cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3052. doi:10.1158/1538-7445.AM2015-3052
Abstract 1752: 6-Methoxyethylamino-numonafide (MEAN) inhibits hepatocellular carcinoma as a single agent or in combination with sorafenib
Authors: Yanning Liu, Guohua Lou, John Norton, Chen Wang, Irawati Kandela, Shuai Tang, Min Huang, Michael Avram, Richard Green, Andrew Mazar, Daniel Appella, Zhi Chen, Sui Huang
Journal: Cancer Research (2015)

Abstract Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide and the incidence is increasing rapidly in the United States, tripling over the past 3 decades. Unfortunately, chemotherapeutic treatment strategies against localized and metastatic HCC are very ineffective, leading to a high mortality from the disease. Sorafenib is the sole FDA approved chemotherapeutic currently used clinically for the disease and it shows limited efficacy and substantial toxicity. We have developed a small molecule, 6-methoxyethylamino-numonafide (MEAN), which is highly effective in two murine xenograph models of human HCC. MEAN is more effective in tumor growth inhibition and less toxic than sorafenib at the same concentration. MEAN, at efficacious doses, does not significantly affect animal body weight and does not significantly induce liver damage as determined by the serum levels of liver enzymes at the experimental endpoint. NCI60 cell assay analyses using the COMPARE algorithm indicate that, at IC50 concentration, MEAN does not significantly correlate with any of the small molecules in the 60 cell assay database (correlation&amp;lt;0.5), suggesting novel modes of action in tumor inhibition. MEAN suppresses some of the well-known oncogene expression and enhances the expression of a subset of tumor suppressors. MEAN remains effective against cancer cells that are drug resistant due to expression of P-glycoprotein drug efflux pumps and has a favorable single dose pharmacokinetic profile. In summary, MEAN is effective against HCC tumor growth and is an excellent candidate for future development as therapeutic agent for management of HCC. Citation Format: Yanning Liu, Guohua Lou, John Norton, Chen Wang, Irawati Kandela, Shuai Tang, Min Huang, Michael Avram, Richard Green, Andrew Mazar, Daniel Appella, Zhi Chen, Sui Huang. 6-Methoxyethylamino-numonafide (MEAN) inhibits hepatocellular carcinoma as a single agent or in combination with sorafenib. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1752. doi:10.1158/1538-7445.AM2015-1752
Exceptional In Vitro Activity of CD37 Antibodies In CLL
Authors: Thorsten Zenz, Matthias Volden, Theresa Mast, Karsten Nordhausen, Dirk Winkler, Andrea Schnaiter, Andreas Buehler, Karl-Heinz Heider, Volker Reichardt, Hartmut Döhner, Stephan Stilgenbauer
Journal: Blood (2010)
Dasatinib for Chronic Phase Chronic Myeloid Leukemia After Failure of Imatinib In Korean Patients.
Authors: Ha Yeon Lee, Myung-Hee Chang, Chul Won Jung, Dong Hwan (Dennis) Kim, Won Seog Kim, Seok Jin Kim, Kihyun Kim, Jun Ho Jang, Sung-Soo Yoon, Kyoo-Hyung Lee, Hyeoung Joon Kim, Joo-Seop Chung, Sang Kyun Sohn
Journal: Blood (2010)
Mesenchymal Stem Cells for Treatment of Severe Acute and Extensive Chronic Graft-Versus-Host Disease.
Authors: Katarina Le Blanc, Francesco Frassoni, Lynne Ball, Mehmet Uzunel, Edoardo Lanini, Berit Sundberg, Helena Lonnies, Giorgio Dini, Andrea Bacigalupo, Franco Locatelli, Willem E. Fibbe, Olle T.H. Ringden
Journal: Blood (2005)
Aqueous outflow - A continuum from trabecular meshwork to episcleral veins
Authors: Teresia Carreon, Elizabeth van der Merwe, Ronald L. Fellman, Murray Johnstone, Sanjoy K. Bhattacharya
Journal: Progress in Retinal and Eye Research (2016)

In glaucoma, lowered intraocular pressure (IOP) confers neuroprotection. Elevated IOP characterizes glaucoma and arises from impaired aqueous humor (AH) outflow. Increased resistance in the trabecular meshwork (TM), a filter-like structure essential to regulate AH outflow, may result in the impaired outflow. Flow through the 360° circumference of TM structures may be non-uniform, divided into high and low flow regions, termed as segmental. After flowing through the TM, AH enters Schlemm's canal (SC), which expresses both blood and lymphatic markers; AH then passes into collector channel entrances (CCE) along the SC external well. From the CCE, AH enters a deep scleral plexus (DSP) of vessels that typically run parallel to SC. From the DSP, intrascleral collector vessels run radially to the scleral surface to connect with AH containing vessels called aqueous veins to discharge AH to blood-containing episcleral veins. However, the molecular mechanisms that maintain homeostatic properties of endothelial cells along the pathways are not well understood. How these molecular events change during aging and in glaucoma pathology remain unresolved. In this review, we propose mechanistic possibilities to explain the continuum of AH outflow control, which originates at the TM and extends through collector channels to the episcleral veins.
MPTH-27A LARGE-SCALE UCLA GLIOMA TISSUE MICROARRAY IDENTIFIES EMP2 AS A NOVEL BIOMARKER FOR GBM THAT CORRELATES WITH OVERALL PROGNOSIS
Authors: Panayiotis Pelargos, Yu Qin, Brittany Voth, Kimberly Thill, Lawrance Chung, Robert Prins, Linda Liau, Nolan Ung, Seyed Hojat, William Yong, Lynn Gordon, Madhuri Wadehra, Isaac Yang
Journal: Neuro-Oncology (2015)

BACKGROUND: Glioblastoma multiforme (GBM) is a deadly disease with a survival of approximately 15 months.Epithelial membrane protein 2 (EMP2) is correlated with advanced disease and adverse outcomes in several cancers and has recently been found to be expressed in GBM.
Recent Significance of Allogeneic Hematopoietic Stem Cell Transplantation for Adult T Cell Leukemia/Lymphoma (ATL)
Authors: Masahito Tokunaga, Nobuaki Nakano, Ayumu Kubota, Mayumi Tokunaga, Takahiro Itoyama, Torahiko Makino, Shogo Takeuchi, Yoshifusa Takatsuka, Atae Utsunomiya
Journal: Blood (2014)
Multilevel Molecular Profiling to Dissect Resistance to Tyrosine Kinase Inhibitors in TEL/ABL Positive Acute Lymphoblastic Leukemia
Authors: Olga Zimmermannova, Veronika Kanderova, Daniela Kuzilkova, Fridtjof Lund-Johansen, Eliska Doktorova, Jiri Petrak, J.H. Frederik Falkenburg, Tomas Kalina, Julia Starkova, Jan Trka, Jan Zuna, Marketa Zaliova
Journal: Blood (2014)
Patterns and Prognostic Impact of PI3K-AKT Pathway Activation, Regulation and Downstream Activity in AML Using Reverse Phase Proteins Arrays (RPPA).
Authors: Steven M. Kornblau, YiHua Qiu, Shana L. Palla, Zeng Zhihong, Wenjing Chen, Gautam Borthakur, Kevin R. Coombes, Marina Konopleva
Journal: Blood (2007)
Allogeneic Stem Cell Transplantation (SCT) with Reduced-Intensity Conditioning (RIC) in Children with Malignancies: A Retrospective Study from the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC).
Authors: Anne Sirvent, Andre Baruchel, Catherine Paillard, Helene Esperou, Pierre Bordigoni, Jacques-Olivier Bay, Gerard Michel, Reza Tabrizi, Jean-Pierre Vannier, Claire Galambrun, Agnes Buzyn, Jean-Hugues Dalle
Journal: Blood (2005)
Abstract 3429: Patient awareness of staging in cancer diagnosis: Helpful or hurtful
Authors: Ariel Schaap, Rashi Aggarwal, Jason Domogauer
Journal: Cancer Research (2015)

Abstract Objective: In this study we will examine if education levels of English-speaking patients in New Jersey Medical School's Outpatient Cancer Center is correlated with awareness of their disease. Next we will examine their level of depression, as well as explore if patients’ awareness of their disease is correlated with depression. Lastly we will explore if patients’ awareness of their disease is correlated with their level of self-perceived stigma regarding depression. Methods: This project is part of a larger questionnaire-based study examining depression prevalence and its associated stigma in cancer patients. Participants consisted of English-speaking oncology patients at New Jersey Medical Cancer Center outpatient oncology clinics. The parts of the questionnaire that I analyzed for this study: 1. What is your level of education? 2. What stage was your cancer in when you were diagnosed? 3. Currently is your cancer localized to a single area or has it metastasized to other areas? 4. Depression symptoms were assessed using the CES-D depression scale. 5. Self-stigma was assessed using Depression Stigma Scale. Summary: An increased level of education was associated with a significantly increased level of awareness of cancer staging, linear by linear association (1, N = 223) = 9.353 p = .002. 31% of patients did not know their cancer staging and/or whether or not it had metastasized. Out of the people who were aware of staging only 28.5% were depressed, whereas 34.8% of people who were unaware of staging and/or metastasis were depressed, Fisher Exact test p = .308. While this is not significant, the trend is an important one to be aware of and to examine in future research. Patients who were aware of their staging and metastasis had a lower mean self-perceived stigma than patients who were unaware of staging and/or metastasis, 14.87 and 15.19 respectively, t(216) = .32, p = .031 Conclusion: Doctors must recognize that patients in low educated demographic areas, such as Newark, require special attention and need to be evaluated on whether or not they understood what the doctor explained to them about their disease. Further research should focus on analyzing the exact reasons underlying this lack of patient knowledge. In addition, the correlation between lack of knowledge and depression should continue to be explored as patient control and autonomy can improve patient outcomes. Doctors should recognize that patients may have a high self-perceived stigma associated with depression, which can act as a barrier to treatment. Future studies should look at how to dispel that stigma. Citation Format: Ariel Schaap, Rashi Aggarwal, Jason Domogauer. Patient awareness of staging in cancer diagnosis: Helpful or hurtful. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3429. doi:10.1158/1538-7445.AM2015-3429
Abstract 5937: Clinical Spectrum and Course of Idiopathic Hypertrophic Cardiomyopathy in Children. A Multicentre Cohort Study of Italian Patients
Authors: Elena Biagini, Giuseppe Limongelli, Camillo Autore, Paolo Spirito, Giuseppe Pacileo, Gabriele Egidy, Francesco Formisano, Luca Ragni, Gianni Quarta, Francesca Terzi, Claudia Borghi, Fernando M Picchio, Raffaele Calabro, Claudio Rapezzi
Journal: Circulation (2008)

Since limited information is available on long-term course of childhood idiopathic hypertrophic cardiomyopathy (IHCM), we investigated this question. We reviewed database records of childhood IHCM ...
Abstract 4174: Molecular changes in the EGFR pathway and RAS/RAF genes identify subtypes of metastatic and nonmetastatic colorectal cancer associated with different outcomes
Authors: Abeer A. Bahnassy, Salem E. Salem, Nehal Hussein, Hend F. Yousif, None Marwa, Iman Al-Desouky, Abdel-Rahman N. Zekri
Journal: Cancer Research (2015)

Abstract Background: Categorization of colon cancers into distinct subtypes using a combination of pathway-based biomarkers and RAS/RAF mutations provides better insight into the variability in patient outcomes. We assessed the incidence, prognostic and predictive values of KRAS/BRAF mutations and some EGFR pathway genes in metastatic and non- metastatic CRC (mCRC and nmCRC) patients from Egypt. Methods: 396 CRC patients (240 metastatic&amp; 156 non metastatic) were assessed for KRAS/BRAF mutations by conventional PCR and immunohistochemistry (IHC). EGFR, PI3K, MEK and ERK expressions were assessed by quantitative real time PCR (qPCR) and IHC. Results were correlated to standard prognostic factors, response to treatment overall and disease free survival (OS&amp;DFS). Results: We detected KRAS mutations in 47.7% (27% in codon 12, 35.6% in codon 13 and 14.3% in 12/13), BRAF in 31.3% and EGFR in 54.6% of the cases. KRAS and EGFR were significantly higher in mCRC cases (p = 0.012&amp; p = 0.045). Tumors were categorized into 4 genetically different groups: EGFR-/KRAS+, EGFR-/KRAS-, EGFR+/KRAS-, EGFR+/KRAS+ (30.3%,28.3%,24%, 17.4%). Significant correlations were found between EGFR, KRAS/BRAF mutations and PI3K-RNA in metastatic and non metastatic CRC (0.02&amp;&amp;lt;0.001). In mCRC, correlations were found between 1) RAS mutations and all markers except EGFR (0.028&amp;&amp;lt;0.001), 2) RAF and MEK/EGFR (0.045&amp;&amp;lt;0.005), 3) PI3K and all genes (&amp;lt;0.001) except BRAF, 4) ERK and MEK (&amp;lt;0.001). In nmCRC, correlations were reported between 1) PI3K and EGFR (p&amp;lt;0.001), 2) RAS and MEK/ERK (p&amp;lt;0.001), 3) MEK and ERK (p&amp;lt;0.001), 4) EGFR and PI3K (p&amp;lt;0.001). DFS significantly correlated with K13RAS mutations, PI3K and positive family history (p&amp;lt;0.05). OS correlated with K13 RAS/BRAF mutation, PI3K and age (p&amp;lt;0.05). Conclusions: KRAS/BRAF mutations and aberrations in EGFR pathway contribute differently to the development and progression of metastatic and non metastatic CRC cases in Egypt. These markers could be used for monitoring patients during treatment with conventional chemotherapy regimens and can provide candidates for targeted therapy. Citation Format: Abeer A. Bahnassy, Salem E. Salem, Nehal Hussein,Hend F. Yousif, Marwa, Iman Al-Desouky, Abdel-Rahman N. Zekri. Molecular changes in the EGFR pathway and RAS/RAF genes identify subtypes of metastatic and nonmetastatic colorectal cancer associated with different outcomes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4174. doi:10.1158/1538-7445.AM2015-4174
A Distinctive MicroRNA Signature Characterizes Acute Myeloid Leukemia with Translocation (8;16)(p11;p13) and MYST3-CREBBP Rearrangement
Authors: Marina Díaz Beyá, Alfons Navarro, Tania Díaz, Bernat Gel, Mireia Camós, Marta Pratcorona, Montserrat Torrebadell, María Rozman, Margherita Maffioli, Mariano Monzó, Jordi Esteve
Journal: Blood (2010)
86. Comparison of CNS Transduction by Different AAV Capsids in Mouse and Non-Human Primate
Authors: Martin Goulet, Justin Aubin, Adrian P. Kells, Qin Su, Shipeng Yuan, Kartik Ramamoorthi, Rob Kotin, James McLaughlin, Guangping Gao, Dinah W.Y. Sah
Journal: Molecular Therapy (2015)

Adeno-associated viral (AAV) vectors are a platform of great potential for therapeutic gene delivery. One of the major challenges regarding AAV gene therapy is to deliver the transgene of interest to target cells at levels that result in expression that is both safe and effective. The AAV vector capsid is a strong determinant of gross biodistribution, cellular tropism, transduction efficiency and transgene expression. Neurodegenerative disorders such as Friedreich's ataxia present a significant challenge in developing an effective gene therapy that provides clinically relevant distribution and expression in the central nervous system (CNS). Friedreich's ataxia is caused by an expanded GAA trinucleotide repeat in the first intron of the frataxin gene which leads to reduced levels of frataxin, a key mitochondrial protein. Pathological features include progressive degeneration of dorsal root ganglia and sensory axons, dorsal columns, Clarke's column, and dentate nuclei of the cerebellum. Elevation of frataxin in these anatomic regions is a therapeutic approach that is likely to be beneficial in addressing the neurological components of disease. However, AAV-mediated gene delivery for therapeutic expression of frataxin in the CNS and distribution to Clarke's column and cerebellar dentate nuclei, have not been investigated to a significant extent. Furthermore, a direct head-to-head comparison of multiple capsids (AAV2, 5, 6, 9, DJ, DJ8, rh10) with intrathecal dosing in non-human primates, a key translational step for therapy, has not been reported previously. Here, we used these 7 capsids to package a single-stranded (ss) vector genome (vg) containing the human frataxin gene driven by the chicken β-actin promoter, and compared frataxin expression in mouse and then non-human primate CNS. In the mouse, dramatic differences in frataxin expression were observed after intracerebroventricular injection of these capsids. Intrastriatal injection in the mouse resulted in frataxin expression patterns that differed qualitatively from those observed after intracerebroventricular injection. In vivo data from both mouse and non-human primate studies will be reported. These results will not only guide the selection and optimization of a capsid for AAV gene therapy of Friedreich's ataxia, but also provide useful information for engineering capsids for other CNS disorders.