tbuckley/cabot-search huggingface dataset:
PTH-094 Providing a small bowel endoscopy service: the fall and rise of enteroscopy?
Authors: R Sidhu, M E McAlindon, M Imran, K Drew, S Hardcastle, D S Sanders
Journal: Gut (2010)

<h3>Introduction</h3> There are few centres in the UK which currently offer a one stop service with capsule endoscopy, double balloon and push enteroscopy. There are no published data on the comparisons between the three modalities in the UK. We evaluated the impact of the small bowel service on diagnostic yield and patient management. We also investigated the demand for each modality on the provision of the service. <h3>Methods</h3> Data were collected on patients that underwent push enteroscopy (PE, since January 2002), capsule endoscopy (CE, since June 2002) and double balloon enteroscopy (DBE, inception of service, July 2006). Data were collected on demographics, indication of referral and diagnosis obtained including subsequent follow-up/outcomes. The modality of investigation performed depended on the referral indication and the location of the suspected pathology. However the majority of patients had CE first followed by enteroscopy (either PE or DBE). The demand and diagnostic yield for each modality and impact on patient management was also assessed over the same time period. <h3>Results</h3> 1246 CE9s, 247 PE9s and 102 DBE9s were performed over 93 months. Forty per cent of the referrals originated from outside the region. The overall diagnostic yield was 34% for CE, 39% for PE and 43% for DBE, respectively (p=0.15). The diagnostic yield was highest for the indication of obscure gastrointestinal bleeding (OGB) for both PE (p&lt;0.001) and CE (p&lt;0.001). In patients who underwent CE for OGB, the most common finding was angioectasia in 24% of patients while small bowel tumours accounted for 3.2% of patients (n=19) and commoner in those ≤60 years of age (p=0.01). Management was altered in 24% of patients that underwent CE, 20% that underwent PE and in 33% of patients that underwent DBE. For all 3 modalities, this was in the form of referral for surgery, initiation or step up of inflammatory bowel disease directed therapy and biopsy or application of thermocoagulation/haemostasis techniques to lesions seen at enteroscopy. The increasing demand for CE has resulted in a relative decline in the number of PEs performed (p&lt;0.001) while the demand for DBE is rising particularly for lesions considered beyond the reach of PE. In 2008, for every 24 CE9s performed, one patient underwent DBE locally. <h3>Conclusion</h3> All three modalities are complementary to one another. The use of CE first line followed by PE/DBE as an adjuvant to CE for either obtaining histology or therapeutic intervention ensures efficient use of the small bowel service. With the rise in the number of centres providing a CE service, the demand for DBE is also expected to increase. Hence, there should also be a provision to meet this rising demand at a national level.
MELISSE, a Large Multicentric Observational Study to Determine Criteria and Risk Factors of Thromboembolism for Patients with Multiple Myeloma Treated with Immunomodulator Drugs
Authors: Xavier Leleu, Laurent Daley, Philippe Rodon, Cyrille Hulin, Ahmad AL Jijakli, Olivier Fitoussi, Charles Dauriac, Bruno Lioure, Laurent Voillat, Borhane Slama, Maya Hacini, Régis Costello, Jean Claude Eisenmann, Carine Chaleteix, Olivier Decaux, Anne Lamblin, Patrick Natta, Jean Paul Fermand, Philippe Moreau
Journal: Blood (2010)
Abstract 3117: Hsa-miR-140-5p inhibits colorectal cancer stem cell invasion and metastasis by suppressing Smad2 and autophagy
Authors: Haiyan Zhai, Andrew Fesler, Jingfang Ju
Journal: Cancer Research (2015)

Abstract Colorectal cancer is one of the most common cancers and frequently metastasizes to the liver. TGF-β signaling has been shown to regulate cancer metastasis by promoting epithelial to mesenchymal transition and cancer stem cell (CSC) phenotypes. Smad2 is a key element downstream of TGF-β. In this study, we showed that hsa-hsa-miR-140-5p-5p directly targets Smad2 and overexpression of hsa-miR-140-5p in colorectal cancer cell lines decreases Smad2 expression level, which leads to decreased level of cell invasion and proliferation, as well as increasing cell cycle arrest. Ectopic expression of hsa-miR-140-5p in colorectal CSCs inhibited CSC growth and sphere formation in vitro by disrupting autophagy, an essential process for cancer cell survival and chemoresistance. We have systematically identified the targets of hsa-miR-140-5p involved in autophagy. Furthermore, overexpression of hsa-miR-140-5p in CSCs abolished the tumor formation as well as metastasis in vivo by using subcutaneous xenografts and tail vein injection of CSCs in NOD/SCID mice. In addition, there is a progressive loss of hsa-miR-140-5p expression from normal colorectal mucosa to primary tumor tissues, with further reduction in liver metastatic tissues, quantified by qRT-PCR. The functional and clinical significance of hsa-miR-140-5p suggests that it is a key regulator in colorectal cancer progression and metastasis. As a result, it may have potential as a novel therapeutic molecule to treat colorectal cancer. Citation Format: Haiyan Zhai, Andrew Fesler, Jingfang Ju. Hsa-miR-140-5p inhibits colorectal cancer stem cell invasion and metastasis by suppressing Smad2 and autophagy. [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 3117. doi:10.1158/1538-7445.AM2015-3117
Abstract 1941: Distinct roles of c-Jun N-terminal kinase (JNK) isoforms in skin cancer
Authors: Lili Du, Tinghu Zhang, Tamer Kaoud, Nathanael Gray, Kevin Dalby, Kenneth Y. Tsai
Journal: Cancer Research (2015)

Abstract The c-Jun-N-terminal kinases (JNKs), are activated by stress, growth factors and cytokines, and are encoded by three separate genes (JNK 1, 2, and 3), with 10 total isoforms. Our published data has demonstrated that off-target effects on JNK signaling by BRAF inhibitors (BRAFi) are important for the induction of cutaneous squamous carcinoma (cuSCC). Overexpression of JNK2, has been found to promote transformation of keratinocytes, also suggesting an important role of JNK signaling pathway in promoting tumor development. However, it is still unclear how different JNK isoforms, especially ubiquitously expressed JNK1 and JNK2, really function in skin cancer. To delineate the specific roles of JNK1 and JNK2, we expressed C116S mutants, which rendered them insensitive to the pan-JNK inhibitor JNK-IN-8, without affecting their activity. Wild-type and mutant JNK1 and JNK2 were transduced into cuSCC (SRB1) and keratinocyte (HaCaT) cell lines and application of JNK-IN-8 enabled chemical-genetic dissection of JNK1 and JNK2 activity. JNK-IN-8 significantly attenuated UV-induced apoptosis by 80-90% in SRB1 and HaCat cells overexpressing WT JNK1, WT JNK2 or C116S JNK2 mutant compared to vehicle control while having only a slight effect (0-10%) on cells overexpressing C116S JNK1 mutant, suggesting JNK1 is the key player in UV- induced apoptosis. This difference served as the basis for a gene expression profiling study in which we identified differentially expressed genes regulated by JNK1 vs. JNK2. We also showed that the Leucine-zipper and sterile-α motif kinase (ZAK), which is a MAP3K, is an important upstream activator of JNK-mediated UV-induced apoptosis in skin cancer. To probe how ZAK activates JNK signaling, we knocked down ZAK in SRB1 and HaCaT cells with lentiviral shRNA. Following UV exposure, we found that both JNK1 and JNK2 activation occurred with JNK1 activity peaking within 6 hours and JNK2 activity sustained over 24 hours. In ZAK knockdown cells, JNK1 activation was selectively suppressed, suggesting that ZAK preferentially activates JNK1 in this context. In conclusion, our results indicate that JNK signaling pathway, part of which is regulated by ZAK, plays a critical role in skin cancer. JNK1 and JNK2 exert opposing influences that center on the regulation of apoptosis and cell proliferation in skin cancer. Citation Format: Lili Du, Tinghu Zhang, Tamer Kaoud, Nathanael Gray, Kevin Dalby, Kenneth Y. Tsai. Distinct roles of c-Jun N-terminal kinase (JNK) isoforms in skin cancer. [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 1941. doi:10.1158/1538-7445.AM2015-1941
IMP: a pipeline for reproducible reference-independent integrated metagenomic and metatranscriptomic analyses
Authors: Shaman Narayanasamy, Yohan Jarosz, Emilie E. L. Muller, Anna Heintz-Buschart, Malte Herold, Anne Kaysen, Cédric C. Laczny, Nicolás Pinel, Patrick May, Paul Wilmes
Journal: Genome biology (2016)

Existing workflows for the analysis of multi-omic microbiome datasets are lab-specific and often result in sub-optimal data usage. Here we present IMP, a reproducible and modular pipeline for the integrated and reference-independent analysis of coupled metagenomic and metatranscriptomic data. IMP incorporates robust read preprocessing, iterative co-assembly, analyses of microbial community structure and function, automated binning, as well as genomic signature-based visualizations. The IMP-based data integration strategy enhances data usage, output volume, and output quality as demonstrated using relevant use-cases. Finally, IMP is encapsulated within a user-friendly implementation using Python and Docker. IMP is available at http://r3lab.uni.lu/web/imp/ (MIT license).
Palifermin Reduces Estimated Downstream Costs of Autologous Stem Cell Transplant (SCT): Analysis of Phase 3 Trial Results.
Authors: L.S. Elting, Y.C.T. Shih, P.J. Stiff, W. Bensinger, S.B. Cantor, C. Cooksley, R. Spielberger
Journal: Blood (2004)
Quantification of the Minimal Residual Disease in Pediatric Philadelphia-Positive Acute Lymphoblastic Leukemia
Authors: Cristian Ferri, Cecilia Riccheri, Julieta Bietti, Alejandra Cedola, Michele Bianchini, Luis Alberto Aversa, Sandra Pennesi, Carolina Belli, Gustavo Milone, Irene B Larripa
Journal: Blood (2014)
The potential of circulating microRNA (miRNA) levels as a biomarker in drug development: An analysis of tumor-serum samples from patients on a phase I trial of saracatinib-paclitaxel (P)-carboplatin (C).
Authors: D. S. Tan, S. Aamdal, G. Freyer, R. J. Jones, S. B. Kaye, E. Pujade-Lauraine, J. Fog, M. Wrang Teilum, C. Glue, A. Baker, U. A. Emeribe, P. Elvin, C. Stephens, M. Stuart, J. Walker, E. Boven
Journal: Journal of Clinical Oncology (2011)

10548 Background: miRNAs are small non-coding RNAs of 20-25 nucleotides with diverse regulatory functions including proliferation, cell differentiation and apoptosis. Unlike mRNA, miRNAs are stable in circulation, potentially offering valuable insights to pharmacologic modulation of drug targets and cell physiology, overcoming some of the challenges associated with tumor biopsies. We explored circulating miRNAs as a biomarker in the Phase I trial of saracatinib (AZD0530) in combination with standard doses of P and/or C (NCT00496028). Methods: Formalin fixed paraffin embedded (FFPE) tumor (n=29) and serum samples (n=69; 22/69 paired pre- and post-treatment) were profiled using Exiqon LNA based QPCR system (n=730 miRNAs) to analyze miRNA expression. Tumor samples analyzed included colorectal (CRC; n=8), ovary (7), pancreas (3), breast (2), esophagus (3), bladder (2), bone, lung, prostate, stomach (1 each). Results: Pre-analytical quality control revealed 28/29 tumor and 55/69 serum samples suitable for miRNA assessment. Unsupervised clustering of miRNAs derived from FFPE samples revealed discriminatory potential to identify the tissue of origin. Importantly, while distinct miRNA profiles were associated with certain tumor types, only selected miRNAs were concordant in matched tumor-serum samples, eg high miR192 and miR194 in CRC. We further examined specific miRNAs that may function as surrogate markers of Src kinase activity, eg miR194 (Li et al. Oncogene 2009;28:4272–83). Although there was no significant change in miR194 levels in 22 paired serum samples, when we excluded CRC patients which typically have high miR194 levels, significant increase in miR194 was seen post exposure to treatment (n=14, P=0.037). Conclusions: Circulating miRNA profiles can be reliably and reproducibly measured in serum, with some degree of tumor-serum concordance. Validation of miRNAs regulated by drug-targeted pathways should consider tumor-of-origin artifacts; adoption of a ‘miRNA profile’ may circumvent this concern. The role of circulating miRNAs as a biomarker in clinical trials warrants further evaluation.
Abstract LB-031: Biochemical profiling of cancer-associated KRAS mutants: clues towards an understanding of differential clinical outcomes
Authors: John C. Hunter, Deepak Gurbani, Martin Carrasco, Anuj Manandhar, Sudershan Gondi, Kenneth Westover
Journal: Cancer Research (2015)

Abstract As one of the first identified and most commonly activated oncogenes, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) has been a focus of cancer research for many decades. Despite progress in our understanding of RAS biology, significant questions remain unanswered regarding observed differences in clinical outcomes between tumors harboring different KRAS mutations. In an attempt to understand these clinical differences we characterized the pertinent biochemical properties of the most commonly observed KRAS mutants including, nucleotide exchange rate, intrinsic and GTPase activating protein (GAP)-stimulated GTP hydrolysis rate and affinity for one of the enzyme's primary downstream effectors, Raf kinase. We additionally solved high resolution crystal structures of four of these mutants and attempt to explain the observed biochemical differences between the mutants in the context of these structures. Based on the individual biochemical properties of each KRAS mutant, we propose a classification scheme to predict the propensity of the various mutants to activate Raf-kinase and respond to therapies targeting this downstream signaling pathway. Citation Format: John C. Hunter, Deepak Gurbani, Martin Carrasco, Anuj Manandhar, Sudershan Gondi, Kenneth Westover. Biochemical profiling of cancer-associated KRAS mutants: clues towards an understanding of differential clinical 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 LB-031. doi:10.1158/1538-7445.AM2015-LB-031
Phase III Trial of Fludarabine, Cyclophosphamide, and Rituximab Vs. Pentostatin, Cyclophosphamide, and Rituximab in B-Cell Chronic Lymphocytic Leukemia
Authors: Craig Reynolds, Nicholas Di Bella, Roger M. Lyons, William J Hyman, Gary L. Lee, Donald A Richards, Gerald J. Robbins, Mark Vellek, Kristi A Boehm, Feng Zhan, Lina Asmar
Journal: Blood (2008)
Abstract 2741: The risk of cancer among children with birth defects
Authors: Philip J. Lupo, Michael E. Scheurer, Sharon E. Plon, Logan E. Spector, Beth A. Mueller
Journal: Cancer Research (2015)

Abstract Background: Although a few genetic syndromes are known to increase cancer risk in children, the presence of a structural birth defect in the absence of these syndromes is increasingly being recognized as a risk factor for childhood cancer. To better understand associations of specific defects and cancer types, we conducted a population-based assessment to avoid biases often present in studies relying on single clinics, referral centers, or treatment networks. Methods: Records of those diagnosed with cancer &amp;lt;20 years of age between 1984 and 2013 in Washington State were linked to their birth certificates (N = 4,043). Birth records of children without cancer were selected at a ratio of 10:1 for a comparison group. Information on birth defects was obtained from birth records. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for: 1) having any reported defect and the risk of childhood cancer; 2) having any reported defect and the risk of specific cancer types; and 3) having a specific defect and the risk of specific cancer types. All models were adjusted for birth year. Results: Having any birth defect was associated with a 50% increased risk of childhood cancer overall (OR 1.5, 95% CI 1.2-1.8), and specifically for leukemia (OR = 1.7, 95% CI 1.2-2.4); neuroblastoma (OR = 1.9, 95% CI 1.0-3.5); soft tissue sarcoma (OR = 2.0, 95% CI 1.2-3.5); and germ cell tumors (OR = 3.0, 95% CI 1.6-5.5). Some specific defects were associated with specific cancer types: central nervous system (CNS) tumors with CNS defects (OR&amp;gt;4.0); leukemia, neuroblastoma, renal tumors, and soft tissue sarcoma with gastrointestinal anomalies (ORs&amp;gt;9.0); renal tumors and urogenital anomalies (OR&amp;gt;4.0); and soft tissue sarcoma with adactyly, polydactyly, or syndactyly (OR&amp;gt;8.0). Conclusions: Consistent with prior studies, structural birth defects were associated with increased cancer risk. Pooling similar data from many regions will increase power to identify specific associations in order to inform molecular studies examining possible common developmental pathways in the etiologies of birth defects and cancer, and will provide information that can be translated into screening strategies for children at high risk of developing cancer. Funding: Cancer Prevention Research Institute of Texas RP140258 and Alex's Lemonade Stand Foundation Citation Format: Philip J. Lupo, Michael E. Scheurer, Sharon E. Plon, Logan E. Spector, Beth A. Mueller. The risk of cancer among children with birth defects. [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 2741. doi:10.1158/1538-7445.AM2015-2741
Trends in Regenerative Medicine: Repigmentation in Vitiligo Through Melanocyte Stem Cell Mobilization
Authors: Stanca A. Birlea, Gertrude‐E. Costin, Dennis R. Roop, David A. Norris
Journal: Medicinal Research Reviews (2016)

Abstract Vitiligo is the most frequent human pigmentary disorder, characterized by progressive autoimmune destruction of mature epidermal melanocytes. Of the current treatments offering partial and temporary relief, ultraviolet (UV) light is the most effective, coordinating an intricate network of keratinocyte and melanocyte factors that control numerous cellular and molecular signaling pathways. This UV‐activated process is a classic example of regenerative medicine, inducing functional melanocyte stem cell populations in the hair follicle to divide, migrate, and differentiate into mature melanocytes that regenerate the epidermis through a complex process involving melanocytes and other cell lineages in the skin. Using an in‐depth correlative analysis of multiple experimental and clinical data sets, we generated a modern molecular research platform that can be used as a working model for further research of vitiligo repigmentation. Our analysis emphasizes the active participation of defined molecular pathways that regulate the balance between stemness and differentiation states of melanocytes and keratinocytes: p53 and its downstream effectors controlling melanogenesis; Wnt/β‐catenin with proliferative, migratory, and differentiation roles in different pigmentation systems; integrins, cadherins, tetraspanins, and metalloproteinases, with promigratory effects on melanocytes; TGF‐β and its effector PAX3, which control differentiation. Our long‐term goal is to design pharmacological compounds that can specifically activate melanocyte precursors in the hair follicle in order to obtain faster, better, and durable repigmentation.
Ciclosporine and Metotrexate Reduce the Risk of High Grade Acute Gvhd after Busulfan, Fludarabine and Anti-Thymocyte Globulin conditioning Regimen in Comparison with Cyclosporine Alone
Authors: Reza Tabrizi, Stephane Vigouroux, Arnaud Pigneux, Thibaut Leguay, Krimo Bouabdallah, Marie-Sarah Dilhuydy, Carine Foucaud, Pierre-Yves Dumas, Axelle Lascaux, Mohamed Zarrouk, Jean-Michel Boiron, Fontanet Bijou, Pascal Turlure, Cyril Melot, Gerald Marit, Noel Milpied
Journal: Blood (2008)
A Vulnerable Moment
Authors: Donald A. Misch
Journal: Annals of Internal Medicine (2016)

On Being a Doctor20 December 2016A Vulnerable MomentDonald A. Misch, MDDonald A. Misch, MDFrom University of Colorado School of Medicine, Aurora, Colorado.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-0438 Audio Reading - “A Vulnerable Moment” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Vulnerable Moment," by D.A. Misch. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail It's been over 35 years, so some of the details are hazy. The key elements of the event, however, remain as clear as the day they occurred. It was in the first month of my internal medicine residency, a month out of medical school, when I clearly killed my first patient.She was a Hispanic woman in her 40s who, by all rights, should have died long before. Having undergone two renal transplantations, she had experienced just about every complication imaginable on the immunosuppressive drugs prescribed to prevent rejection. On this day, she looked ill, as usual. She was feverish, ... Author, Article, and Disclosure InformationAffiliations: From University of Colorado School of Medicine, Aurora, Colorado.Corresponding Author: Donald A. Misch, MD, 1240 Pine Street, Suite 213, Boulder, CO 80302; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “A Vulnerable Moment” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Vulnerable Moment," by D.A. Misch. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Cited byVoices from the Front Lines: An Analysis of Physicians’ Reflective Narratives about Flaws with the ‘System’Voices from the Front Lines: An Analysis of Physicians’ Reflective Narratives about Flaws with the ‘System’ 20 December 2016Volume 165, Issue 12Page: 887-888KeywordsChildrenImmunosuppressivesLungsMotivationProteinsPulmonary arteriesRenal transplantationResidencyThoraxWalking ePublished: 20 December 2016 Issue Published: 20 December 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...