tbuckley/cabot-search huggingface dataset:
Abstract LB-250: Development of a miR34-based cancer therapy.
Authors: Chris Daige, Jason Wiggins, Leslie Priddy, Kevin Kelnar, Jane Zhao, Andreas Bader, David Brown
Journal: Cancer Research (2013)

Abstract miR-34 is a tumor suppressor miRNA that functions within the p53 pathway and regulates the expression of more than twenty oncogenes, including MET, MYC, WNT, and MYB. We have created a mimic of miR-34 called miR-Rx34 that induces cell cycle arrest, senescence, and apoptosis in cancer cells. Transient transfection of miR-Rx34 significantly reduces the proliferation of cancer cells derived from patients with liver, lung, breast, colon, and pancreatic cancers as well as melanoma, lymphoma, and multiple myeloma. miR-Rx34 has been encapsulated in an anionic liposome to produce a particle called MRX34 that has a diameter of ~120 nm. Intravenous injections of MRX34 causes dose-dependent increases in miR-34 levels in liver tumor, lung tumor, liver, lung, spleen, and other highly vascularized tissues in mice without inducing an immune response. Systemic delivery of MRX34 causes complete tumor regression in two orthotopic models of liver cancer. The exceptional potency of MRX34 likely results from its capacity to stimulate the p53 pathway and down-regulate genes in the wnt/B-catenin, MET, MAPK, and VegF pathways in liver tumors. The no adverse effects level observed for MRX34 in IND-enabling toxicology studies in monkeys and rats are 10-100-fold higher than the doses that produce complete tumor regression in mice, suggesting that the drug candidate will have a broad therapeutic window in cancer patients. Clinical studies with MRX34 that are expected to begin in early 2013 will provide the first measure of the therapeutic potential of a tumor suppressor miRNA. Citation Format: Chris Daige, Jason Wiggins, Leslie Priddy, Kevin Kelnar, Jane Zhao, Andreas Bader, David Brown. Development of a miR34-based cancer therapy. [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 LB-250. doi:10.1158/1538-7445.AM2013-LB-250
DEFINING PATIENT-CENTRED PROFESSIONALISM IN GASTROENTEROLOGY
Authors: S Wright
Journal: Gut (2013)

<h3>Introduction</h3> The UK IBD audit 3rd round (RCP, 2011) shows that there has been sustained improvement in patient-centred care in terms of clinician commitment to improved quality of care and the provision of specialist IBD nursing and patient education for patients with IBD. This study explores the meaning of the concept ‘patient-centred professionalism9 in gastroenterology. <h3>Aims/Background</h3> The objectives of this study are: 1. To clarify the meaning of patient-centred professionalism in terms of how it relates to professional practice and patient-professional interaction in gastroenterological outpatient clinic consultations. 2. To define the concept according to the views and experiences of healthcare professionals, stakeholders and IBD patients. 3. To create materials which may support and enhance optimal professional practice in outpatient clinics for patients with IBD. <h3>Method</h3> A qualitative study using observation and semi-structured interviews. Ethnographic observation was conducted in 8 outpatient clinics from within one local health board (Abertawe Bro Morgannwg University Health Board). Clinics were led by consultant physician gastroenterologists; surgeons, specialist nurses and joint colorectal MDT clinics. A total of 31 consultations were observed with IBD patients aged between 18–70 years old. A total of 40 in-depth qualitative interviews were conducted with IBD patients; healthcare professionals and eminent stakeholders in gastroenterology. Ethnographic fieldnotes from observation and transcripts from interviews were analysed using a thematic analysis approach. <h3>Results</h3> Key characteristics of patient-centred professionalism in gastroenterology have been elicited and categorised into thematic areas including shared decision making; transparency, openness and honesty; information and knowledge transfer and integrated approaches to care. Patients9 descriptions of experiences of consultations with healthcare professionals are vivid and reveal both best practice in gastroenterological practices in secondary care as well as unexpected views about encounters with the medical profession. An output from this study involves the creation of materials to support gastroenterological outpatient clinic consultations to enhance the optimal professional practice and patient-professional communication. <h3>Conclusion</h3> Patients9 understandings of patient-centred professionalism, coupled with healthcare professionals and stakeholder understandings of the concept, offer the opportunity to develop enhanced consultations in gastroenterological outpatient clinics.
Abstract 499: EGFR expression correlates with response to photodynamic therapy in esophageal cancer cells
Authors: Pei-Wen Yang, Mien-Chie Hung, Mien-Chie Hung, Ying-Hao Wang, En-Chi Tung, Yung-Chie Lee, Jang-Ming Lee
Journal: Cancer Research (2010)

Abstract Photodynamic therapy (PDT) has been demonstrated as an effect treatment modality for early esophageal cancer by using a photo-sensitizer which induces a cytotoxic photoreaction in tumor cells after exposure to a specific wave-length of light. However, the mechanism is still poorly understood regarding the response to PDT for the patients with esophageal cancer. Epidermal growth factor receptor (EGFR) activation is known to induce resistance to many anti-cancer treatments. In this study, we intend to investigate the role of EGFR in esophageal cancer treated with PDT. The PDT-induced cell death is based on the accumulation of a photosensitizing drug in specific cells. Followed by irradiation with visible light (usually red light), the drug-accumulation cells will induce apoptosis or necrosis. In our study, we observed PDT induced cell death of human esophageal carcinoma cells, CE48T/VGH in a dose-dependent manner by incubating increasing amounts of photosensitizer photofrin (0 to 20 μg/ml) under the expose of 630 nm red light (0 to 180 mJ/ cm2) by MTT assay. We found the protein expression of EGFR was decreased with increased amounts of photofrin. The phenomenon was more obvious under light treatments. EGFR expression was not recovered in the presence of proteasome inhibitors indicating that the reduction of EGFR was not mediated by proteasome-dependent pathway. However, the amount of EGFR mRNA was similar in PDT treated and un-treated cells by RT-PCR analysis. To further clarify the role of EGFR expression in PDT resistant ECa cells, we selected the PDT resistant esophageal cancer (CE48T/VGH) cells by incubated with 15 μg /ml photofrin under the 54 mJ/ cm2 or 108 mJ/ cm2 of red light exposure. At 25 days post PDT treatment, the cells was collected and indicated as PDTR 1-1 and PDTR 1-2 respectively. Compared to wild type CE48T/VGH cells, PDTR 1-1 and PDTR 1-2 display 16% and 13 % resistances respectively when incubated with 15 μg /ml photofrin under 108 mJ/ cm2 light treatment. Correlated with the resistance, we found that EGFR protein expression was increased in both PDTR 1-1 and PDTR 1-2 (about 18% compared to wild type cells). Based on our preliminary findings, EGFR expression may be involved in PDT resistance in esophageal cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 499.
The Thrombocytopenic Effect of Sustained High-Dosage Prednisone Therapy in Thrombocytopenic Purpura
Authors: Phin Cohen, Frank H. Gardner
Journal: New England Journal of Medicine (1961)

THE beneficial effect of corticosteroids in the treatment of idiopathic thrombocytopenic purpura in adults has been proved.1 , 2 in approximately 60 per cent of cases, the platelet count can be returned to normal levels with corticosteroids. Once the platelet count is normal, the practice in this laboratory has been to taper the dose of corticosteroids until the lowest maintenance level is found at which the remission is sustained. Because of the self-limited nature of some cases, permanent remission is achieved, and corticosteroids may be eliminated. Other cases require long-term maintenance therapy to sustain the remission, and for many of these patients . . .
SEGURIDAD DEL PROPOFOL ADMINISTRADO POR GASTROENTERÓLOGOS Y PERSONAL DE ENFERMERÍA EN LA UNIDAD DE ENDOSCOPIA
Authors: L Achécar Justo, X García Aguilera, A González Pino, AI Vilches Vázquez, JM Villalba Fernández, C Durand Castañón, G Guerrero Estepa, M Van Domselaar
Journal: Endoscopy (2012)

Introducción: Persisten controversias sobre la utilización del propofol por no anestesistas en endoscopia digestiva a pesar de la evidencia existente sobre su seguridad. Objetivo: Describir nuestra experiencia sobre la seguridad y efectividad del propofol administrado por el personal médico y de enfermería de endoscopia. Método: Estudio prospectivo, en el que se recogió sexo, edad, peso, talla, riesgo anestésico, dosis de propofol, tipo de exploración, complicaciones, satisfacción del médico y paciente de las endoscópicas realizadas bajo sedación con propofol en el período junio-julio del 2012. Resultados: Se realizaron 639 exploraciones, 348 colonoscopias (54,7%) y 291 (45,5%) gastroscopias. En todas se empleó propofol en bolo, asociando fentanilo solo en colonoscopia. El 48,8% de los pacientes tenía riesgo anestésico ASA I; 49,1%, ASA II; y 2,2%, ASA III. El 26% presentaban un índice de masa corporal ≥30kg/m2.El 20,7% de las exploraciones fueron terapéuticas y el 33,3% se realizaron en pacientes de más de 65 años. La dosis media de propofol fue 124±63mg. La dosis media en los mayores de 65 años 95±46mg (P=0,001). En gastroscopia la dosis media fue de 117±54mg y en colonoscopia de 127±61mg (P=0,03). Se registraron incidencias en 13 pacientes (2,1%), todas leves (8 desaturación y 5 bradicardia, recuperados con maniobra extensión del mentón y administración de atropina respectivamente). Ocho de las incidencias (6 desaturación y 2 bradicardia) ocurrieron en mayores de 65 años, siendo el 85,4% ASAII (P=0,14). El 97,5% de las exploraciones fueron completas y ninguna se suspendió por complicaciones relacionadas con la sedación. La satisfacción global registrada por el endoscopista fue muy buena-buena en 99,7% y regular en 0,3%, siendo la tolerancia del paciente “muy buena” en el 99,2%. Conclusión: El empleo de propofol administrado por el endoscopista asistido por el personal de enfermería es una técnica efectiva y segura de sedación.
Abstract B46: Essential roles of SIRT1 for BCR-ABL transformation and genetic mutations
Authors: Zhiqiang Wang, Hongfeng Yuan, Hardik Modi, Ravi Bhatia, WenYong Chen
Journal: Cancer Research (2009)

Abstract Resistance of cancer stem cells and acquired genetic mutations are daunting challenges facing targeted cancer therapy, but the underlying mechanisms are not clear. This is best exampled by the tyrosine kinase inhibitor imatinib that effectively treats chronic myelogenous leukemia (CML) whereas resistance develops due to persistence of CML stem/progenitor cells and acquired mutations of BCR-ABL. SIRT1 is a mammalian stress response gene homologous to yeast silent information regulator 2 (Sir2), a nicotinamide adenine dinucleotide (NAD+) dependent protein deacetylase, and is involved in regulation of a variety of cellular functions including survival, glucose homeostasis and fat metabolism through deacetylating histones and non-histone target proteins. Here we demonstrate that BCRABL transformation activates SIRT1 in hematopoietic stem/progenitor cells in both clinical CML patients and a CML-like disease mouse model. Inhibition of SIRT1 by gene knockdown or pharmacological inhibitors suppresses CML cell proliferation and induces apoptosis in vitro. SIRT1 knockdown inhibits growth of CML tumor xenograft in immunodeficient mice. Homozygous knockout of SIRT1 gene inhibits BCR-ABL transformation of mouse bone marrow cells and the development of a CML-like myeloproliferative disease. We show that through deacetylation of Ku70, SIRT1 promotes BCR-ABL mutations upon imatinib treatment and de novo genetic mutations upon DNA damage. Our results suggest an essential role of SIRT1 for BCR-ABL oncogenic transformation and promoting cancer genome instability, and have implication for targeting SIRT1 to overcome resistance. These findings not only improve our understanding of SIRT1 functions in tumorigenesis, but also have translational implication for targeting SIRT1 for overcoming resistance in cancer treatment. Citation Information: Cancer Res 2009;69(23 Suppl):B46.
Hepatobiliary Scan Showing Type II Choledochal Cyst
Authors: Jeffrey Wienke, Steven Falen, William McCartney
Journal: Clinical Nuclear Medicine (2001)

Nuclear medicine hepatobiliary scintigraphy is well established for the evaluation of right upper quadrant pain in cases of possible acute cholecystitis. The authors present a case of type II choledochal cyst shown on a hepatobiliary scan in a patient with possible acute cholecystitis.
Abstract 3982: Super-resolution imaging of drug delivery to live cells using real-time structured illumination microscopy
Authors: Jonathan Lefman, Tai Cheuk, Belhu Metaferia, Patricia Tsang, Keana Scott, Stephan Stranick, Javed Khan
Journal: Cancer Research (2010)

Abstract Imaging the effects of drug delivery in live cells is most often performed by confocal microscopy, which has a resolution limited by the diffraction of light. Here, we report the development of a novel method for imaging drug delivery to live cells using real-time super-resolution microscopy in wide-field mode. Structured illumination microscopy (SIM) is one of several super-resolving microscopy techniques and is capable of imaging beyond the resolution of conventional microscopy to less than 100 nm. In SIM, each super-resolution (SR) image is computationally constructed from a dataset of numerous raw images. Due to the computational time required for SR image construction, datasets are usually post-processed to avoid slowdowns during the acquisition process. Although post-processing is convenient, this approach has limited use since SR images are not available during image acquisition and thus cannot be utilized for real-time evaluation of the sample. Utilizing SR images in real-time is particularly important when objects of interest are smaller than the resolution limit of conventional microscopy. Applications such as determining optimal focus and finding desirable regions of interest are depending on real-time feedback to user. When performing real-time SIM imaging live cells, image acquisition, processing, and the display of SR images must occur in rapid succession thereby reducing the effects of molecular movement. To achieve the data processing speed necessary for real-time imaging of live cells, we utilized a graphics processing unit (GPU) to perform high-speed SR image construction. Each function for processing SIM data was optimized for parallel operation using GPU kernels. Excluding data transfer overhead, the actual GPU processing time for synthesizing the SR image was 45 milliseconds. Compared with parallel processing on a multi-core computer (CPU), using the GPU achieved a 45-fold increase in processing speed. Overall, data throughput using the GPU attained an 8-fold speed increase over CPU processing, thus allowing real-time high resolution imaging. We applied this SIM platform to record the action of nocodazole on microtubule depolymerization in HeLa cells. We are currently developing this real-time imaging method to investigate the delivery and release mechanism of therapeutic cargoes contained within nanoparticles. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3982.
Abstract 4599: The RING E3 ligase BCA2 is regulated by estrogen and co-expressed with estrogen receptor in breast cancer cells
Authors: Fathima R. Kona, Stephanie Bacopulos, Yutaka Amemiya, Arun K. Seth, Angelika M. Burger
Journal: Cancer Research (2010)

Abstract The Breast Cancer Associated gene 2 (BCA2) protein contains a RING H2 finger and a zinc finger near the N-terminus. The presence of the RING domain allows BCA2 to function as an E3 ligase. RING finger proteins play critical roles in mediating the transfer of ubiquitin and ubiquitin-like modifiers to substrates; such modifications are pivotal in regulating protein homeostasis and basic cellular processes such as gene-transcriptional regulation. The RING domain in BCA2 is known to act as an E3 ligase in its auto-regulation, and is suspected to play a role in the modification of other proteins. In a cohort of 945 primary invasive breast cancers examined for estrogen receptor-alpha (ER) and BCA2 expression, 67% were found to be ER-positive, 74% of which also exhibited strong nuclear BCA2 protein expression (p = 0.004). In this study, we examined potential mechanism(s) underlying BCA2 and ER co-expression at transcriptional and protein levels. Estrogen-responsive and non-responsive breast cancer cell lines were used as model systems. To investigate whether BCA2 is an estrogen responsive gene, BCA2 and ER-positive T47D breast cancer cells were cultured in medium containing charcoal-stripped fetal calf serum supplemented with 10 nM and 100 nM 17β-estradiol respectively over a 72-hour time course. Northern and Western blots showed a 17β-estradiol-associated induction of BCA2 mRNA and protein within 72 hrs. Moreover, when ER is ectopically or stably expressed in ER and BCA2-negative MDA-MB-231 cells, prominent BCA2 expression is detected, suggesting that ER is responsible for induction of BCA2 transcription. To investigate a possible interaction of BCA2 and ER at a transcriptional level, bioinformatic analysis of the BCA2 promoter region revealed ER and PR binding sites as well as possible sites of general transcription factors. Together our data indicates that BCA2 is upregulated in response to estrogen and that BCA2 expression can be rescued by the introduction of ER, suggesting that ER and BCA2 may be participating in crosstalk at the transcriptional level. Further investigations into this phenomenon are necessary to determine the possibility of the development of drugs targeting BCA2 in order to manipulate ER. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4599.
CARDIAC MAGNETIC RESONANCE ASSESSMENT OF MAXIMAL LEFT VENTRICULAR WALL THICKNESS DIFFERS SIGNIFICANTLY FROM ECHOCARDIOGRAPHY IN HYPERTROPHIC CARDIOMYOPATHY
Authors: Brett Wesley Sperry, Dermot Phelan, Paaladinesh Thavendiranathan, Patrick Collier, Zoran Popovic, Brian Griffin, Milind Desai
Journal: Journal of the American College of Cardiology (2015)
The Infectivity of<i>Cryptosporidium parvum</i>in Healthy Volunteers
Authors: Herbert L. DuPont, Cynthia L. Chappell, Charles R. Sterling, Pablo C. Okhuysen, Joan B. Rose, Walter Jakubowski
Journal: New England Journal of Medicine (1995)

Small numbers of Cryptosporidium parvum oocysts can contaminate even treated drinking water, and ingestion of oocysts can cause diarrheal disease in normal as well as immunocompromised hosts. Since the number of organisms necessary to cause infection in humans is unknown, we performed a study to determine the infective dose of the parasite in healthy adults.After providing informed consent, 29 healthy volunteers without evidence of previous C. parvum infection, as determined by the absence of anti-cryptosporidium-specific antibodies, were given a single dose of 30 to 1 million C. parvum oocysts obtained from a calf. They were then monitored for oocyst excretion and clinical illness for eight weeks. Household contacts were monitored for secondary spread.Of the 16 subjects who received an intended dose of 300 or more oocysts, 14 (88 percent) became infected. After a dose of 30 oocysts, one of five subjects (20 percent) became infected, whereas at a dose of 1000 or more oocysts, seven of seven became infected. The median infective dose, calculated by linear regression, was 132 oocysts. Of the 18 subjects who excreted oocysts after the challenge dose, 11 had enteric symptoms and 7 (39 percent) had clinical cryptosporidiosis, consisting of diarrhea plus at least one other enteric symptom. All recovered, and there were no secondary cases of diarrhea among household contacts.In healthy adults with no serologic evidence of past infection with C. parvum, a low dose of C. parvum oocysts is sufficient to cause infection.
Abstract P2-04-01: Development of mouse breast cancer models based on induced cancer stem cells (iCSC).
Authors: Y Takamoto, N Onishi, K Kai, H Saya
Journal: Cancer Research (2012)

Abstract Breast cancer is one of the leading causes of death in women worldwide. To develop novel therapeutic approaches for the refractory cases, the mouse models which recapitulate the tumor tissues biologically and pathologically similar to human breast cancer are required. Although xenograft models of established cell lines in immune-deficient mice are frequently used for preclinical experiments, such xenograft models are not sufficient because the heterogenous structure based on the microenvironment and the intrinsic characteristics of cancer cells is not correctly formed. In this study, we have established induced cancer stem cells (iCSC) from normal mouse mammary stem/progenitor cells through minimal required genetic manipulations and generated mouse breast cancer models by inoculating the iCSCs in the mammary fat pads. Initially, we established iCSC by introducing the H-RasV12 into Ink4a/Arf-knockout mammary stem/progenitor cells and this iCSC formed tumor similar to human triple negative breast cancer in mouse. This finding suggested that two genetic events, an activation of oncogenic signal and a tumor suppressor inactivation, are required for generating the breast cancer iCSC. Anaplastic Lymphoma Kinase (ALK) gene, which encodes a receptor tyrosine kinase, was reported to be amplified and/or overexpressed up to 86% of patients in inflammatory breast cancer, and pleiotrophin (PTN), which is a physiological ligand for ALK, was also shown to be highly expressed in about 60% of human breast cancers. Therefore, we hypothesized that ALK pathway is involved in tumorigenesis of breast cancers and, then, attempted to generate iCSC by using ALK gene. Interestingly, we found that one of the naturally occurring mutations of ALK is sufficient for generating iCSC and tumor formation in vivo without any prior tumor suppressor inactivation. The ALK-induced iCSCs developed highly aggressive breast cancers in mice. Furthermore, the tumor formation was significantly suppressed when the ALK-induced iCSCs were generated by using mammary stem/progenitor cells derived from mouse deficient in CD44 which is a CSC marker. We have recently revealed a role of CD44, in particular that of a variant isoform (CD44v), in the protection of CSCs from high levels of oxidative stress derived from both tumor cells and their microenvironment (Cancer Cell 19: 387–400, 2011; Cancer Res 72: 1438–1448, 2012; Nat Commun 3: 883, 2012). We will discuss the underlying mechanism of ALK-induced tumorigenesis and a role of CD44 in the CSC functions. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-04-01.
1296 SAFETY AND EFFICACY OF THE PAN-CASPASE INHIBITOR IDN-6556 IN THE TREATMENT OF NONALCOHOLIC FATTY LIVER AND INSULIN RESISTANCE
Authors: W. Lu, A. Eguchi, D. Sirbu, C. Jonhson, P. Contreras, A. Wree, M. Lazic, D. Povero, A. Feldstein
Journal: Journal of Hepatology (2013)