tbuckley/cabot-search huggingface dataset:
259. Parathyroid Hormone Gene Modified Mesenchymal Stem Cells for Hypoparathyroidism
Authors: Ruoyu Jiang, Na Zhao, Xianghui He
Journal: Molecular Therapy (2015)

Hypoparathyroidism is a prominent complication of total thyroidectomy for thyroid cancer. Hypocalcemia significantly decrease the quality of life of patients with hypoparathyroidism. Medical management with calcium supplements and activated vitamin D analogues increase risk of renal complications. Hormone replacement is an alternative. In this study, we investigated the possibility of management hypoparathyroidism using parathyroid hormone gene modified mesenchymal stem cells. Rat model of hypoparathyroidism was established through parathyroid gland removing by operation. Human prepro-PTH gene was amplified by RT-PCR from parathyroid adenoma and cloned into lentiviral vector. In order to express functional PTH by non-parathyroid cells. Specific mutation was introduced into the prepro-PTH gene. PTH expression was determined after transfection of 293T cells with the vector. Rat adipose tissue-derived mesenchymal stem cells were cultured and infected with PTH gene-expressing lentiviral vectors. The therapeutic effect of PTH gene modified MSCs on experimental hypoparathyroidism will be presented.
Serum Free Light Chain Levels Post Allogeneic Stem Cell Transplantation Are Associated With Improved Overall Survival In Patients With Acute Myeloid Leukemia
Authors: Sophie Lee, Philip Young, Joanne Croudace, Ben Abbotts, Ladan Adie, Jane Nunnick, Ram Malladi, Guy Pratt, Charles Craddock, Stephen Harding, Paul Moss
Journal: Blood (2013)
PWE-042 20 year follow up of british twin pairs with inflammatory bowel disease: Abstract PWE-042 Table 1
Authors: H Gordon, T Orchard, S Ng, A Steel, A Cocker, M Harbord
Journal: Gut (2015)

<h3>Introduction</h3> IBD twin studies have shown similar disease phenotype within concordant pairs. Longitudinal follow up suggests pairs with CD remain concordant for location whereas twins with UC diverge.<sup>1</sup>This study is a retrospective longitudinal analysis of UK twin pairs with IBD. <h3>Method</h3> The UK IBD Twin and Multiplex Registry was searched for twin pairs who took part in a previous twin study. Data from 1994 and 2014 was reviewed. The following were analysed: zygosity, concordance, Montreal classification, admissions, surgical history. <h3>Results</h3> Demographics: N=94 twin pairs. UC:CD 48:46. Mean age 59. Pair Concordance: 3 previously discordant pairs became concordant. The mean time between diagnosis was 9.1 years. Montreal Classification: Concordant Pairs: There were no mixed CD:UC pairs. Of the 17 concordant pairs, 10 had complete information from both twins in both datasets. IBD: A was identical in 6/12 (50%) concordant pairs. CD: L was identical in 3/6 (50%) pairs in both 1994 and 2014. B was only available from 2014, and was identical in 3/6 (50%) pairs. P was identical in 2/5 (40%) twins in 1994 and 3/7 (43%) twins in 2014. UC: A was identical in 3/4 pairs (74%). L was identical in 4/4 (100%) pairs in 1994 and 2014. All IBD sufferers: UC: Disease classified as proctitis decreased from 1994 to 2014 (30.4% vs 17.9%), with a corresponding increase in pancolitis (41.1% vs 50%). CD: Cases classified as L3 increased from 6/52 (11.5%) to 22/53 (41.5%). Presence of perianal disease also increased (9.6% vs 23.1%). Extraluminal manifestations increased from 4/109 (3.7%) to 13/112 (11.6%). Surgery: <b>Concordant pairs:</b>Concordant twin pairs were concordant for history of previous surgery in 9/12 (75%) pairs in 1994 and 7/14 (50%) pairs in 2014. <b>All IBD: </b>In 1994 32/109 (29.4%) IBD sufferers had undergone surgery, increasing to 52/112 (49.1%) in 2014. Admission: <b>Concordant pairs:</b>Concordant twins were concordant for history of admission in 10/14 (71.4%) pairs in 1994 and 10/15 (66.7%) pairs in 2014. <b>All IBD: </b>46/109 (42.2%) IBD sufferers had at least one admission in 1994; this increased to 76/112 (67.9%) in 2014. <h3>Conclusion</h3> Pair concordance of this cohort supports that heritability of CD is greater than UC. Within concordant pairs with CD, disease location is less correlated than in other cohorts. Conversely, concordant pairs within UC were more similar and converged over time. Sample size limited analysis. Disease progressed over time. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Halfvarson, <i>et al</i>. Longitudinal concordance for clinical characteristics in a Swedish-Danish twin population. IBD 2007
Abstract 3779: Mutational analysis of MCPH1 C-terminal tandem BRCT domain reveals residues essential for cell cycle arrest
Authors: Volha A. Golubeva, Nicholas T. Woods, Alvaro N.A. Monteiro
Journal: Cancer Research (2015)

Abstract In this study, the C-terminal tandem BRCT domain of human microcephalin 1 protein (MCPH1) was mutagenized in Saccharomyces cerevisiae yeast to identify residues critical for the cell cycle arrest. Deleterious variants in MCPH1 causing the loss of the protein function are associated with primary microcephaly, characterized by decreased cerebral cortex size and mild mental retardation. The tandem BRCT domain of MCPH1 (amino acids 640-833) recognizes phospho-serine/threonine motifs, including □-H2AX, necessary for DNA damage response and cell cycle regulation. Expression of this region of human MCPH1 tethered to DNA in yeast through the Gal4 DNA binding domain (and not through the interaction with the Gal4 activation domain), results in growth inhibition and a small colony phenotype. To detect the essential residues of the MCPH1 tandem BRCT, mutations were randomly introduced into this region using error-prone polymerase chain reaction. The mutants were then transformed into yeast and transformants showing abrogation of the small colony phenotype were isolated and the specific mutations were assessed by sequencing. Screening revealed 34 missense, 4 nonsense, and 8 frameshift variants, and one large deletion of 72 base pairs. The 34 missense variants were further analyzed in silico by alignment with the BRCA1 tandem BRCT. Out of 34 missense variants, four (T694A, L755P, F756V, and S819P) were identified in two or more colonies. One of the mutated residues (T653) is involved in direct hydrogen bonding with □-H2AX, which is likely disrupted by the amino acid change induced during mutagenesis (T653I). Interestingly, when aligned with BRCA1, 16 (47%) of MCPH1 missense variants matched to a corresponding site in BRCA1 previously reported as a missense variant with a functional impact. MCPH1 residues 653, 756, and 819 all corresponded to amino acids in BRCA1 known for their likely pathogenicity. Thus, this study identifies functional determinants in MCPH1 C-terminal domain potentially involved in cell cycle regulation. Taken together, our results suggest that variants in BRCT domain containing proteins, can be clinically annotated by making comparative alignments with the conserved residues of BRCA1 BRCT. Structural inference using BRCT paralogs might aid in the clinical annotation for variants lacking genetic data. Citation Format: Volha A. Golubeva, Nicholas T. Woods, Alvaro N.A. Monteiro. Mutational analysis of MCPH1 C-terminal tandem BRCT domain reveals residues essential for cell cycle arrest. [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 3779. doi:10.1158/1538-7445.AM2015-3779
The Analysis of HDAC Inhibitor, Vorinostat Efficacy against Wild Type and BCR-ABL Mutant Positive Leukemia Cells in Monotherapy and in Combination with a Pan-Aurora Kinase Inhibitor, MK-0457
Authors: Seiichi Okabe, Tetsuzo Tauchi, Shinya Kimura, Taira Maekawa, Kazuma Ohyashiki
Journal: Blood (2008)
Trends in the adoption of robotic technology in the surgical management of prostate cancer: A population-based analysis.
Authors: Steven Lee Chang, Wei Jiang, Benjamin I. Chung
Journal: Journal of Clinical Oncology (2012)

258 Background: The adoption of the da Vinci Surgical System (Intuitive Surgical, Inc) for robotic surgery requires a substantial financial investment by hospitals, acquisition of new surgical skills by surgeons, and demand from patients. Although the benefits of this technology have been previously described, the prevalence and adoption rate for the treatment of prostate cancer is not currently known. We performed a population-based analysis to determine how the introduction of robotic technology has altered the surgical management of prostate cancer. Methods: We analyzed patient-level data from the Prospective Rx Comparative Database (Premier, Inc., Charlotte, NC), which collects data from over 600 non-federal hospitals throughout the United States. We captured all men who underwent a radical prostatectomy between January 1, 2003, and December 31, 2010, based on the International Classification of Disease, 9 th edition. Radical prostatectomies utilizing the da Vinci Surgical System were identified by a detailed review of the hospital charge data. Descriptive analysis with univariate and multivariate statistical analyses were performed. Results: Prior to 2006, &lt;10% of radical prostatectomies were performed with robotic surgery. Beginning in 2006 there was a rapid rise in adoption reaching 56% utilization in 2009 and leveling off in 2010 to 54%. Adjusted analysis demonstrated that the odds of adopting robotic surgery were higher in teaching hospital (odds ratio [OR] 1.45, p&lt;0.001) and hospitals in the Northeast (vs Midwest [OR 2.99, p&lt;0.001]). Smaller hospitals (&lt;200 beds) had a lower likelihood of adopting robotic surgery (OR 0.4, p&lt;0.001). Patient age had no impact on the odds of undergoing robotic radical prostatectomy. Conclusions: Over past 5 years, there has been widespread adoption of robotic surgery in the management of prostate cancer now with just over half of procedures performed with the da Vinci Surgical System. Our analysis suggests that the adoption of robotic surgery has been determined primarily by the acquisition of this technology by hospitals, which was more common in teaching institutions, larger hospitals, and hospitals in the Northeast.
Psychological Symptoms Among Patients With BCR-ABL–Negative Myeloproliferative Neoplasms
Authors: Daniel C. McFarland, Heather Polizzi, John Mascarenhas, Marina Kremyanskaya, Jimmie Holland, Ronald Hoffman
Journal: Journal of the National Comprehensive Cancer Network (2016)

BCR-ABL-negative myeloproliferative neoplasms (MPNs) represent a heterogeneous group of diseases, including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Psychological manifestations among these diseases have not been adequately described.Cross-sectional surveys measuring distress, anxiety, and depression were collected from patients with BCR-ABL-negative MPNs from May 2015 to October 2015. Participants provided demographic information and completed the Distress Thermometer and Problem List (DT&PL) to assess distress and the Hospital Anxiety and Depression Scale (HADS) to assess distress, anxiety, and depression. They provided information on how their MPN affected their lives.Of the 117 participants, 31.2% had PV, 28.4% had ET, 28.4% had MF, and 11.9% had another type of MPN. Time with MPN varied from less than 1 year (7.5%), 1 to 3 years (19.8%), 3 to 5 years (23.6%), 5 to 10 years (19.8%), and more than 10 years (29.2%). Distress averaged 3.14 (SD, 2.83; DT&PL), with 40.4% meeting NCCN criteria for distress, and averaged 8.97 (SD, 7.44; HADS), with 38.5% meeting HADS criteria for distress. Anxiety averaged 5.54 (SD, 4.37), with 31.3% meeting HADS criteria for anxiety. Depression averaged 3.4 (SD, 3.4), with 12.5% meeting HADS criteria for depression. Distress was higher for PV (3.86), MF (3.12), and "other" MPN (4.33) than it was for ET (1.81; P=.016). Distress was more common in non-white patients (P=.015) and those with either PV or MF but not ET (DT&PL ≥4; P=.038). Patients' comments described coping strategies or symptom burden.Distress and anxiety are highly prevalent with BCR-ABL-negative MPNs and may correspond to disease-related symptom burden. These findings deserve further study.
Abstract 4752: Genomic cytometry: Single cell mutation analysis combining PCR with flow cytometry
Authors: William C. Hyun, Adam Sciambi, Maurizio Pellegrino, Dennis Eastburn
Journal: Cancer Research (2015)

Abstract Genomic cytometry is a new technology field combining the high-throughput capabilities of flow cytometry and cell sorting with single-cell multiplex genomic analysis in microfluidic drops. The genomic cytometry method we will describe is PCR-activated cell sorting (PACS). PACS is analogous to Fluorescence-Activated Cell Sorting (FACS) in throughput and the ability to analyze single cells; however, unlike conventional flow cytometric immunophenotyping, PACS uses extremely sensitive microdroplet TaqMan PCR reactions to identify and, if needed, sort cells of interest for additional downstream molecular characterization. This unique approach enables PACS to identify cells based on the presence of transcripts, genomic DNA sequences, mRNA splice variants, SNPs, non-coding RNAs, and other biomarkers not amenable to antibody-based probe detection. PACS can be used to sort and enrich cells targeting single-copy genomic DNA for the analysis of circulating tumor cells (CTCs), intra-tumor heterogeneity, rare stem cells, viral or pathogen infections and genomic characterization of cancer immune system response and disorder. By analyzing individual cells within a population, it is possible to identify rare CTC populations or transient cell states, critical to human health and cancer progression, that are otherwise unobservable by ensemble measurements. With PACS, we identified and sorted prostate cancer cells from a heterogeneous population by performing &amp;gt;132,000 simultaneous single-cell TaqMan RT-PCR reactions targeting vimentin mRNA. Following vimentin-positive droplet sorting and downstream analysis of recovered nucleic acids, we found that cancer-specific genomes and transcripts were significantly enriched. Citation Format: William C. Hyun, Adam Sciambi, Maurizio Pellegrino, Dennis Eastburn. Genomic cytometry: Single cell mutation analysis combining PCR with flow cytometry. [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 4752. doi:10.1158/1538-7445.AM2015-4752
Highly Synergistic Interaction between Farnesyltransferase Inhibitors and the Chk1 Inhibitor UCN-01 to Induce Apoptosis in Human Leukemia Cells through Interruption of Both Akt and MEK/ERK Pathways and Activation of SEK1/JNK.
Authors: Yun Dai, Mohamed Rahmani, Xin-Yan Pei, Payal Khanna, Paul Dent, Steven Grant
Journal: Blood (2004)
Abstract 5289: The role of the immune system in lymph node positive ER+ breast cancer
Authors: Jessica G. Cockburn, Amy Gillgrass, Anita Bane
Journal: Cancer Research (2015)

Abstract Estrogen receptor (ER) positive breast cancer (BC) accounts for 70% of BC diagnoses and is associated with a good outcome when treated with conventional therapies, including tamoxifen. However, there remains a sub-population of patients who undergo relapse within 10 years of diagnosis and do not respond well to standard therapies. While lymph node (LN) status is an important indicator of poor prognosis, additional information is needed to more accurately predict patients who will or will not relapse. Previous genomic studies from our lab have shown that immune response is an important feature of LN+ BCs that do not relapse. In addition, other studies have also examined the role of the immune system in ER+ BC, but due to varying study designs, it is unclear how immune response pertains to ER+ BC relapse. The goal of this project is to characterize immune response in ER+ BC by measuring levels of immune markers using immunohistochemistry (IHC) and RNA expression levels and comparing those to tumour characteristics. We have developed a cohort of retrospective ER+ BC patients with tumour samples available through the Hamilton Health Science tumour bank. Patients were selected for eligibility based on ER status, early stage disease, and having long term clinical follow-up. Clinical charts for each patient were reviewed and pathological, treatment, and outcome data were abstracted. Tumour blocks were obtained and sections stained for haematoxylin and eosin were marked for tumour boarders then used to construct Tissue microarrays (TMA) for IHC assays and RNA is to be extracted from each tumour block. 318 patient samples have been obtained that meet eligibility requirements. Among those, 163 are LN- and 110 are LN+, and the remainder have unknown LN status. Primary endpoint for this study is the development of distant metastasis. Roughly 10% of LN- patients developed distant metastasis within 10 years and roughly 20% of LN+ patients developed distant metastasis. In total, 14% of patients came to endpoint during the study period. TMAs were stained for pathological markers, including ER, PR, HER2, and Ki67 as well as immune markers such as CD8 and CD20. RNA expression levels for each of these were also determined and both were compared with clinical outcome. Here we present a retrospective cohort of ER+ BC patients with 10 years of clinical follow-up data that can be used for IHC and RNA analysis. Further, we have examined the association between immune response and prognosis in lymph node positive ER+ BC patients. Citation Format: Jessica G. Cockburn, Amy Gillgrass, Anita Bane. The role of the immune system in lymph node positive ER+ breast 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 5289. doi:10.1158/1538-7445.AM2015-5289
PTH-093 Small bowel angiodysplasia and lymphangiectasia: a positive association. A novel clinical marker or a shared pathophysiology?: Abstract PTH-093
Authors: J C Macdonald, V Porter, N W Scott, D McNamara
Journal: Gut (2010)

<h3>Introduction</h3> The cause of sporadic angiodysplasia is unknown and the natural history poorly understood. Many lesions are thought to arise from a degenerative process associated with ageing. Most cases of hereditary haemorrhagic telangiectasia appear to result from mutations in two genes, ENG and ACVRL1. These mutations alter the function of 2 key endothelial receptor proteins, endoglin and ALK-1 (part of the transforming growth factor β super-family), which ordinarily play a key role in maintaining vascular integrity. It has been observed that endoglin is over expressed in smooth muscle cells in atherosclerotic plaques, suggesting a role for this protein in plaque progression, atherosclerosis and associated cardiovascular disease. <h3>Methods</h3> To determine if there is an association between angiodysplasia, lymphangiectasias and conditions traditionally associated with atherosclerosis. Consecutive patients referred to a single tertiary referral centre for a capsule endoscopy (CE) over a 3-year period were identified from a dedicated CE database. Indications, findings, demographic information, and the presence of diabetes, ischaemic heart disease, hypertension, hyperlipidaemia were recorded, along with body mass index. Only patients with a complete CE were included for analysis. Logistic regression analysis (LRA) was employed to examine associations between angiodysplasia, lymphangiectasia, patient demographics, obesity and the diseases described. <h3>Results</h3> In all 180 patients were identified, 46 (25%) had angiodysplasia and 47 (26%) lymphangiectasia. Lymphangiectasias were seen in 24 (52%) of 46 with angiodysplasia, in 16 (19%) of 84 with obscure GI bleeding without angiodysplasia and in 7 (14%) of 50 without GI bleeding. LRA confirmed a strong positive association between angiodysplasia and lymphangiectasia, OR 4.42, p&lt;0.003. Angiodysplasias were also associated with increasing age, odds ratio 1.1. There was no correlation with any other patient characteristic (Abstract 093). <h3>Conclusion</h3> This study reveals a strong association between small bowel angiodysplasia, lymphangiectasia and ageing, but not between angiodysplasia and conditions associated with increased risk of atherosclerosis. Lymphangiectasias may represent a useful clinical marker for the presence of angiodysplasia.
Six Courses of Intensified CHOP Plus G-CSF Compared to Eight Courses of Standard CHOP in Patients with Intermediate-Risk Aggressive Non-Hodgkin Lymphoma Results of a Prospective Randomized HOVON Trial.
Authors: Leo F. Verdonck, Gustaaf W. van Imhoff, John M.M. Raemakers, Gregor Verhoef, Mark H.H. Kramer, Gert J. Ossenkoppele, Jeanette K. Doorduijn, Ine A.M.H. Meulendijks, Wessel N. van Wieringen, Pieter Sonneveld
Journal: Blood (2005)
Abstract 1426: Lung epithelial cells induce both phenotype alteration and senescence in breast cancer cells
Authors: Masashi Furukawa, Alan Wells, Sarah Wheeler, Amanda M. Clark
Journal: Cancer Research (2015)

Abstract Purpose: Breast cancer is the most common cancer in women. The lung is one of the most common sites of breast cancer metastasis. While metastatic seeding is often accompanied by a dormancy-promoting mesenchymal to epithelial reverting transitions (MErT), we aimed to determine whether lung epithelial cells can impart this phenotype on aggressive breast cancer cells. Methods: Co-culture experiments of normal lung epithelial cell lines (SAEC, NHBE or BEAS-2B) and breast cancer cell lines (MCF-7 or MDA-MB-231) were conducted. Flow cytometry analysis, immunofluorescence staining for E-cadherin or Ki-67 and senescence associated beta-galactosidase assays assessed breast cancer cell outgrowth and phenotype. Results: Co-culture of the breast cancer cells had different effects on breast cancer cells. The epithelial MCF-7 cells were increased in number but still clustered even if in a slight more mesenchymal spindle morphology. On the other hand, the mesenchymal MDA-MB-231 cells survived but did not progressively grow out in co-culture. These aggressive carcinoma cells underwent an epithelial shift as indicated by cuboidal morphology and increased E-cadherin. Disruption of E-cadherin express in MDA-MB-231 using shRNA prevented this phenotypic reversion in coculture. In addition, we had noted enlarged MDA-MB-231 cells in the co-cultures with SAEC and NHBE but not BEAS-2B cells as suggestion of senescence. A subset of these cells stained with the senescence associated marker β-galactosidase (SA-β-gal). Lung cells limited cancer cell growth kinetics as noted by both (1) some of the cells becoming larger and positive for senescence markers/negative for proliferation marker Ki-67, and (2) Ki-67 positive cells significantly decreasing in MDA-MB-231 and MCF-7 cells after co-culture. Conclusions: Our data indicate that normal lung epithelial cells can drive an epithelial phenotype and suppress the growth kinetics of breast cancer cells by changing their phenotypes.Similar to the hepatocytes, these normal cells may promote the survival, seeding and even dormancy of aggressive mesenchymal carcinoma cells, with phenotypes similar to MDA-MB-231 cells, but also provide progressive signaling when stressed accounting for the spindle morphology and slightly increased growth rates of the epithelial carcinoma cells, such as those MCF-7 represents. In this latter manner, insults the small airway may provoke an outgrowth from dormant breast cancer cells. Citation Format: Masashi Furukawa, Alan Wells, Sarah Wheeler, Amanda M. Clark. Lung epithelial cells induce both phenotype alteration and senescence in breast cancer 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 1426. doi:10.1158/1538-7445.AM2015-1426