tbuckley/cabot-search huggingface dataset:
Abstract 18479: Short- and Long-term Air Pollution Exposure and the Risk for Premature Atrial Contractions and Atrial Fibrillation: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Authors: Wesley T O'Neal, Elsayed Z Soliman, Jimmy T Efird, Suzanne E Judd, Virginia J Howard, George Howard, Leslie A McClure
Journal: Circulation (2015)

Background: Air pollution is associated with an increased risk of cardiovascular disease. This suggests a potential association between air pollution and supraventricular arrhythmias, such as premature atrial contractions (PACs) and atrial fibrillation (AF). However, data from large-scale epidemiologic studies supporting this hypothesis are lacking. Methods: We examined the association between air pollution with PACs and AF in 28,502 (mean age=65 ± 9.4 years; 55% female; 41% black) participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Short-term (2-week) and long-term (1-year) PM2.5 exposure were computed prior to each participants’ baseline visit using individual level geographic information system data at geographic coordinates of participants’ residences. PACs were identified from the baseline electrocardiogram. AF was identified by the study electrocardiogram and by self-reported history of a physician diagnosis. Poisson regression was used to compute relative risk (RR) and 95% confidence intervals (CI) for the association of short- and long-term PM2.5 exposure with PACs and AF, separately. Results: A total of 2,356 (9.2%) participants had evidence of PACs and 2,433 (8.5%) had AF at baseline. Short-term PM2.5 (per 10 μg/m3) exposure was not associated with PACs (RR=1.08, 95%CI=0.99, 1.19) or AF (RR=0.92, 95%CI=0.84, 1.02). Increases in long-term PM2.5 per 10 μg/m3 were associated with PACs (RR=1.35, 95%CI=1.10, 1.65) but not AF (RR=0.96, 95%CI=0.79, 1.17). Conclusion: Long- but not short-term PM2.5 exposure is associated with PACs. This suggests a potential role for long-term PM2.5 exposure in initiating supraventricular arrhythmias that are triggered by PACs but not maintaining sustained rhythm disorders such as AF.
Abstract B18: MicroRNA-21 is involved in pancreatic cancer fibroblast tumor supportiveness
Authors: Andrew Hieu Nguyen, Luyi Li, Paul Toste, Nanping Wu, Timothy R. Donahue
Journal: Cancer Research (2015)

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor survival despite current medical and surgical therapies and has a propensity towards subclinical metastasis even with resectable disease. The tumor microenvironment consists of a network of supporting cells, including tumor-associated fibroblasts (TAFs), which promote tumor invasion and metastasis, and contribute to PDAC’s extremely poor prognosis. MicroRNAs (miRs) have recently emerged as critical players in post-transcriptional regulation of pathways in cancer biology. In this study, we identified miRs in fibroblasts induced by PDAC tumor cells (TCs). Further, we study the stable suppression of one of these miRs in TAFs and the effects upon fibroblast migration and invasion, as well as tumor cell proliferation. Methods: Primary pancreatic fibroblasts were cultured with MIA PaCa-2 TC conditioned media and RNA was analyzed by the NanoString MicroRNA Expression Assay. Stable miR knockdown (KD) was achieved with a stably expressed shRNA anti-microRNA by lentiviral vector. Migration was determined by an 18 hour scratch assay and 24 hour invasion by modified Boyden chamber. TC proliferation was measured by MTT assay. In vivo tumor growth was evaluated by subcutaneous TC and TAF co-implantation in NSG mice. Results: In primary pancreatic fibroblasts, MIA PaCa-2 tumor cells induced 62 miRs &amp;gt;50% increase or 30% decrease in expression. The most prevalent induced miR with 2-fold increase in expression was miR-21. miR-21 KD in TAFs was achieved by introducing stable expression of anti-miR-21, which resulted in a 75% decrease in expression (P&amp;lt;0.001). miR-21 KD TAFs had a &amp;gt;50% decreased ability to migrate (p&amp;lt;0.001) and were 67% less invasive (p&amp;lt;0.001). miR-21 KD TAF conditioned media induced less rapid TC proliferation (p&amp;lt;0.05). Further, in an in vivo model of tumor proliferation, TCs co-implanted with miR-21 KD TAFs showed 45% decreased tumor size (P&amp;lt;0.05), compared to controls. Conclusions: Pancreatic cancer TCs can induce tumor supportive miRs in TAFs. miR-21 KD in PDAC TAFs results in decreased TAF migration and invasion, as well as reduced ability to support in vitro and in vivo tumor growth. Citation Format: Andrew Hieu Nguyen, Luyi Li, Paul Toste, Nanping Wu, Timothy R. Donahue. MicroRNA-21 is involved in pancreatic cancer fibroblast tumor supportiveness. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B18.
Abstract CT208: Preliminary results of a phase II trial of an adenovirus/PSA vaccine in men with recurrent prostate cancer
Authors: David M. Lubaroff, Daniel Vaena, James Brown, Kenneth Nepple, Pamela Zehr, Karen Griffith, Erica Brown, Julie Eastman, Gideon Zamba, Richard Williams
Journal: Cancer Research (2015)

Abstract Introduction and Objectives: A phase II clinical trial of an adenovirus/PSA (Ad/PSA) vaccine was carried out in men with recurrent prostate cancer using two protocols. The objectives of the study were to determine whether the vaccine produced beneficial immune and clinical responses in men with a low burden of tumor. Methods: In Protocol #1 men with recurrent prostate cancer following definitive initial treatment for their disease were placed in one of two arms: Arm A; men received the vaccine alone at days 0, 30, and 60; Arm B; men received the vaccine 14 days after the initiation of androgen deprivation therapy (ADT). In Protocol #2 men with hormone refractory disease received the vaccine alone using the same 3 injection schedule. Each injection consists of 108 pfu of the Ad/PSA vaccine suspended in a collagen matrix. All patients returned at regular intervals for physical, chemical, radiologic, and immunologic evaluations. Results: We enrolled all of our targeted 82 patients, 50 in protocol 1 (25 Arm A, 25 Arm B) and 32 in protocol 2. All patients have been followed a minimum of 12 months with the longest being over 6 years. Eighty nine percent (89%) of all patients produced anti-PSA T cell immune responses; 71% in protocol 1 Arm A, 100% in protocol 1 Arm B, and 100% in protocol 2. Clinically, 58% of patients in protocol 1 Arm A and 75% of patients in protocol 2 demonstrated a decrease in serum PSA or an increase in PSA doubling times (PSADT). As of the submission date the PSA levels of 2 patients declined to 0.07 ng/ml and undetectable (&amp;lt;0.03). Conclusions: Preliminary results of patients thus far studied in a phase II clinical trial of the Ad/PSA vaccine are very encouraging, demonstrating both immunologic and clinical responses to the 3-vaccination therapy. PSA responses indicate at least a decline in the growth and perhaps a destruction of recurrent prostate tumors in men immunized in two separate protocols. Data collection continues that include completion of immune assays on all 82 patients as well as monitoring PSA levels, PSADT, and radiologic changes. Citation Format: David M. Lubaroff, Daniel Vaena, James Brown, Kenneth Nepple, Pamela Zehr, Karen Griffith, Erica Brown, Julie Eastman, Gideon Zamba, Richard Williams. Preliminary results of a phase II trial of an adenovirus/PSA vaccine in men with recurrent prostate 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 CT208. doi:10.1158/1538-7445.AM2015-CT208
Abstract 3824: Human pan-cancer variomes and their epigenetic profiles: Extending beyond the coding region
Authors: John P. Torcivia-Rodriguez, Raja Mazumder
Journal: Cancer Research (2015)

Abstract The identification on different cancer lines of non-synonymous single nucleotide variations (nsSNVs) has exploded as sequencing technology has improved and decreased in expense. The impact of these variations on specific genes is being widely studied thanks to efforts to unify fragmented information about sequence functional sites into comprehensive databases. In additional to sequence functional sites, DNA functional elements have been found throughout the genome - estimates by the ENCODE project of upwards of 80% of the genome - and account for at least some of the biological complexity of life. In this study, we investigate the frequency of cancer related nsSNVs on tissue-independent DNA functional element sites comprised of 14 different functional elements. Out of 1 651 364 cancer related nsSNVs that matched one or more of 5 680 308 total DNA elements collected, we identified a number of variations that significantly affect a broad range of DNA functional elements. Furthermore, we found distinct patterns of site disruptions due to germline and somatic nsSNVs. Pan-cancer analysis across several different cancer types led to the identification of nsSNVs located in functional elements found in 3 or more cancer types. Citation Format: John P. Torcivia-Rodriguez, Raja Mazumder. Human pan-cancer variomes and their epigenetic profiles: Extending beyond the coding region. [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 3824. doi:10.1158/1538-7445.AM2015-3824
Abstract 2732: The role of protein P in hepatocellular carcinoma
Authors: Hongyong Fu, Lianying Guo, Lin HUANG
Journal: Cancer Research (2015)

Abstract Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third leading cause of cancer-related death worldwide. Although treatment options have improved in the past 30 years, 5-year survival rate remains below 20%. To improve the therapeutics of HCC, great efforts are needed in understanding the mechanisms underlying HCC. Protein P, plays an important role in the development of cancer. To clarify the role of P in the development of HCC, we investigated the expression level of P in HCC tissue chips. The results showed that P level is much higher in carcinoma than adjacent tissue, and the overall 5-year survival is much better in P low expression patients than in P high expression patients. P expression was also found to be increased in HCC cell lines, compared with the normal liver cell line. Further, the proliferation of HCC cell lines was suppressed significantly by siRNA-mediated P knockdown in both anchorage dependent and independent growth assays. These data suggested that P is a crucial factor in the development of HCC, which might therefore represent a novel therapeutic target for HCC. Citation Format: Hongyong Fu, Lianying Guo, Lin HUANG. The role of protein P in hepatocellular carcinoma. [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 2732. doi:10.1158/1538-7445.AM2015-2732
Abstract 2051: Regulation of RNA processing by PADI4 pathway
Authors: Chizu Tanikawa, Koji Ueda, Yusuke Nakamura, Koichi Matsuda
Journal: Cancer Research (2015)

Abstract We recently reported that p53 regulated protein citrullination through the transcriptional regulation of PADI4 that converts an arginine residue in proteins to a citrulline residue. In response to DNA damage, p53-PADI4 pathway induced citrullination of NPM1, Histone H4, and Lamin C, and subsequently promoted apoptotic pathway. To elucidate entire roles of p53-PADI4 pathway, we screened novel targets by LC-MS analysis and found that majority of hnRNP family members are citrullinated by ectopic expression of PADI4. LC-MS analysis and specific antibody revealed citrullination of hnRNP G at arginine 223 residue. In addition, citrullination of hnRNP G inhibited interaction with RNA helicases or other hnRNP family members. Citrullination motif analysis revealed the enrichment of D, G, S, E, and A at -1 (56.0%), +1 (55.8%) and +2 (45.8%) position. Since hnRNP family is involved in RNA processing, we conducted RNA sequence analysis by using bone marrow from Padi4+/+ or Padi4-/- mice. As a result, Padi4 was shown to alter the splicing pattern of several genes. Moreover, Padi4-/-p53+/- mice exhibited significantly shorter survival time compared with Padi4+/+p53+/- mice. Our finding revealed a novel role of p53-PADI4 pathway in RNA splicing and human carcinogenesis. Citation Format: Chizu Tanikawa, Koji Ueda, Yusuke Nakamura, Koichi Matsuda. Regulation of RNA processing by PADI4 pathway. [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 2051. doi:10.1158/1538-7445.AM2015-2051
The Cost-Effectiveness of Bortezomib for the Initial Treatment of Multiple Myeloma in the United States.
Authors: Si-Tien Wang, Hui Huang, Hongliang Shi, Mei Sheng Duh, Kristina Chen, Eva Chang, Caroline Korves, Ravinder Dhawan, Andrew Cakana, Helgi van de Velde, Dixie-Lee Esseltine, Louis Garrison
Journal: Blood (2009)
Adding glycopyrronium to beclomethasone plus formoterol improved pulmonary function in COPD
Authors: Brian Budenholzer
Journal: Annals of Internal Medicine (2016)

Source Citation Singh D, Papi A, Corradi M, et al. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting beta2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Lancet. 2016;388:963-73. 27598678
Evaluation comparative randomisée d’un logiciel d’apprentissage personnel de la dissection sous-muqueuse en France et au Japon
Journal: Endoscopy (2016)

La dissection sous-muqueuse endoscopique (ESD) est devenue une méthode de choix pour la résection monobloc des lésions larges. Le problème de cette technique reste son apprentissage long et difficile et qui doit débuter sur modèle animal afin de réduire le risque de perforation chez l’homme. Cependant, la présence d’un expert en ESD est nécessaire pour encadrer l’étudiant. Il en existe de nombreux en Asie, mais peu en Europe. Pour pallier à cela, un logiciel d’apprentissage personnel a été développé par le Pr Yahagi en collaboration avec la société Olympus (Tokyo, Japon). Le but de cette étude était d’évaluer l’impact de cet outil sur la courbe d’apprentissage de l’ESD.
131. Targeted Genome Editing in Spinal Muscular Atrophy
Authors: Annalisa Lattanzi, Matteo Bovolenta, Samia Martin, Vincent Mouly, Fulvio Mavilio
Journal: Molecular Therapy (2015)

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations in the survival-motor-neuron 1 (SMN1) telomeric gene. Deficiencies in the ubiquitous SMN function affect multiple tissues and organs; however neuronal tissue is primarily sensitive, resulting in α-motor neuron degeneration in the ventral horn of the spinal cord with subsequent neuromuscular-junction dysfunction and proximal muscle weakness. The onset of disease and degree of severity are variable in patients and they are determined in part by multiple copies of the centromeric homologue SMN2 that inversely correlate with the phenotypic severity. Indeed, SMN2 gene mainly produces a truncated form SMNΔ7 by aberrant alternative splicing and a small amount (~10%) of the fully active full-length SMN, thus buffering the SMN deficiency. A potential strategy for treating SMA patients is to increase SMN levels in the affected tissues, hence gene therapy and modifiers of SMN2-alternative splicing have proved therapeutic efficacy in SMA animal models. In this study, we explored the possibility of applying targeted genome editing technology to the human SMN locus in order to revert the SMN2 sequence to a SMN1-like sequence that may undergo proper splicing under the the endogenous transcriptional control. The resulting correction would be permanent and lead to longlasting protein production in gene-edited cells. We used the streptococcus pyogenes Cas9-CRISPR system to target the SMN2 gene at different locations. Two main strategies were explored: i) SMN1_exon7 addition/correction by promoting homology-driven DNA repair, ii) SMN2_intron7_ intronic-splicing-silencer (ISS-N1) mutation and correction of SMN2 aberrant splicing, by exploiting the non-homologous end-joining (NHEJ) pathway. Plasmids encoding Cas9-GFP under the control of CMV promoter, and selected gRNAs downstream to the Pol-III U6 promoter (Addgene) were transfected in HEK-293T cell line and in immortalized myoblasts derived from either healthy donors or SMA patients. Transfection efficiency was estimated as percentage of GFP-expressing cells (20-50% and 1-10%, respectively) and nuclease activity detected by Surveyor assay and target site sequencing. In particular, in SMA patient-derived myoblasts we detected mutations (indels) at the level of the induced DNA double-strand break at ~30% frequency. Levels of SMN restoration will be investigated by qPCR of the different species of SMN transcripts and by western blotting of SMN protein. The goal of this study is to provide an in vitro proof of principle of effective gene correction in SMA patient-derived cells. In the context of a multisystemic, complicated disease such as SMA, targeted genome editing strategy could represent an additional therapeutic tool.
A Retrospective Review of Engraftment Data for Tbo-Filgrastim Vs. Filgrastim in Patients Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplantation
Authors: Taylor Teschner, Stephen Lo, Dina Brauneis, Anthony C Shelton, Bhavesh Shah, John Mark Sloan, Cindy Varga, Karen Quillen, Vaishali Sanchorawala
Journal: Blood (2015)
Abstract 2984: Heterogeneous mechanisms of acquired resistance in high grade serous ovarian cancer
Authors: David D L Bowtell
Journal: Cancer Research (2015)

Abstract In contrast to other solid cancers, overall survival for patients with high-grade serous ovarian cancer (HGSC) is little changed over the last 30 years and it has been difficult to advance beyond platinum-based combination chemotherapy. As HGSC are driven by genomic copy number change rather than recurrent point mutation, we undertook whole genome sequence (WGS) analysis of a large HGSC cohort in order to survey structural variation at high resolution. Utilizing 114 tumours from 92 patients, we performed transcriptome, methylation, and miRNA expression analyses to support the WGS data, and compared resistant, refractory, and sensitive primary disease. We evaluated tumour and normal DNA samples from patients with primary refractory, primary resistant or primary sensitive disease to better understand the drivers of these clinical phenotypes. We also characterized paired pre-treatment chemosensitive and post-resistance samples, and end-stage HGSC obtained from patients who underwent a research autopsy. We found that gene breakage involving tumour suppressors such as NF1 and RB1 is a common form of inactivation in HGSC and in other circumstances contributes to acquired chemotherapy resistance in some patients. We found evidence of a chemotherapy footprint in the genome of recurrent tumour samples. We observed a striking degree of diversity of other mechanisms of acquired resistance, including multiple independent germline BRCA1 or BRCA2 reversion events in individual patients, loss of BRCA1 promoter methylation, a shift in molecular subtype to a desmoplastic phenotype, and a recurrent promoter fusion associated with overexpression of a driver of drug resistance, validated in an independent dataset. Collectively our findings underscore the plasticity of the HGSC genome and indicate that pre-empting resistance by modifying current first line therapy or countering it when it emerges will require a diversity of approaches. Citation Format: David D L Bowtell. Heterogeneous mechanisms of acquired resistance in high grade serous ovarian 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 2984. doi:10.1158/1538-7445.AM2015-2984
Abstract 3079: Mechanism of hsa-miR-15a in EMT and chemoresistance in colorectal cancer
Authors: Andrew Fesler, Haiyan Zhai, Jingfang Ju
Journal: Cancer Research (2015)

Abstract Epigenetic alterations such as non-coding microRNAs are critical factors in EMT and chemoresistance. Hsa-miR-15a, as one of the first miRNA identified to be associated with cancer, has been investigated for its role in several types of cancer. We are interested in understanding the molecular and cellular mechanism of hsa-miR-15a in colorectal cancer as hsa-miR-15a is down-regulated in colon cancer and associated with poor patient prognosis. In this study, we have identified several direct key targets of hsa-miR-15a that impact EMT transition, cell cycle and apoptosis. Our results show that the expression of BMI-1, an important regulator of EMT, was suppressed by hsa-miR-15a. The reduction of hsa-miR-15a in colorectal cancer patient samples was significantly inversely correlated with BMI-1 over-expression. Hsa-miR-15a also suppresses the expression of anti-apoptotic protein BCL-2. The suppression of BMI-1, BCL-2 as well as other key targets by hsa-miR-15a has potential for increasing chemosensitivity as well as disrupting cancer stem cell self renewal. In addition, hsa-miR-15a also has potential as a prognostic biomarker in colorectal cancer. This work will provide a further understanding of the mechanism of hsa-miR-15a loss in colorectal cancer and its clinical significance in relationship with its targets and pathways. The functional significance of hsa-miR-15a in regulating key targets and pathways establishes the foundation for hsa-miR-15a as a potential novel therapeutic strategy for treating colorectal cancer. Citation Format: Andrew Fesler, Haiyan Zhai, Jingfang Ju. Mechanism of hsa-miR-15a in EMT and chemoresistance in colorectal 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 3079. doi:10.1158/1538-7445.AM2015-3079
Generation of Functional Regulatory T Cells From Umbilical Cord Blood Naïve T Cells: Potential Role of Hydroxymethylation in the Epigenetic Reprograming and Transcriptional Induction of FoxP3
Authors: Rodrigo Haddad, Josiane Lilian dos Santos Schiavinato, Felipe Saldanha Saldanha-Araújo, Priscila S Scheucher, Amélia G Araújo, Eduardo M. Rego, Dimas T Covas, Marco A. Zago, Rodrigo Alexandre Panepucci
Journal: Blood (2012)
Outcomes In Acute Myeloid Leukemia (AML) Patients Diagnosed with Myeloid Sarcoma with and without Bone Marrow Involvement
Authors: Marc Earl, Alex Fu, Matt Kalaycio, Anjali Advani, Yogen Saunthararajah, Christina Piks, Barb Tripp, Kristy Grimes, Ronald Sobecks, Edward Copelan, Jaroslaw Maciejewski, Mikkael A. Sekeres
Journal: Blood (2010)