tbuckley/cabot-search huggingface dataset:
184. Regulating Mitochondrial Biogenesis Transducers NRF1 To Inhibit Renal Interstitial Fibrosis
Authors: Shu-Fen Liu, Pei-fang Hsieh, Yu-Lin Yang
Journal: Molecular Therapy (2015)

Mitochondrial dysfunction is a newly established risk factor for the development of renal fibrosis. Cell survival and injury repair is facilitated by mitochondrial biogenesis. NRF-1 is a key transcription factor regulating the function of mitochondria. However, the role of this process in renal fibrosis is unknown. Thus, we hereby discuss the correlations of NRF-1 and renal interstitial fibrosis. Materials and Methods: NRK-49F (Normal Rat kidney fibroblast) cells were used. In vitro fibrosis model was established by treatment with transforming growth factor-b1 (TGF-b1). The fibrogenic marker (e.q. fibronectin) and fibrogenic signal proteins (e.q. pSmad2/3,Smad2/3,Smad7) were investigated. Here, we used that two distinct mechanisms regulate NRF1 activition and degradation of NRF1. NRF-1 was transfect by NRF-1 overexpression gene to evaluate NRF-1 activity of the therapeutic effect in renal fibrosis. In addition, NRF-1 was silenced by NRF-1 shRNA to evaluate the significance of NRF-1. ELISA was used to evaluate the secreted fibronectin. Western blot was used to examine the intracellular fibrogenic signal proteins (e.q. pSmad2/3,Smad2/3,Smad7). Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin). Results: Our study demonstrated that expression of NRF-1 is significantly decreased in renal fibrosis. However, transfection with pcDNA-NRF-1 (2mg/mL) expression vector did dramatically reverse TGF-b1-induced cellular fibrosis concomitantly with the suppression of fibronectin (both intracellular and extracellular fibronectin) and fibrogenic signal protein. Intriguingly, NRF-1 shRNA dramatically increased TGF-b1-induced cellular fibrosis. Collectively, these finding suggest that NRF-1 plays a pivotal role on renal cellular fibrosis. Moreover, NRF-1 might act as a novel renal fibrosis antagonist by down-regulating fibrosis signaling in renal fibroblast cells.
Predictors of Death in Contemporary Adult Patients With Eisenmenger Syndrome
Authors: Aleksander Kempny, Cristel Sørensen Hjortshøj, Hong Gu, Wei Li, Alexander R. Opotowsky, Michael J. Landzberg, Annette Schophuus Jensen, Lars Søndergaard, Mette-Elise Estensen, Ulf Thilén, Werner Budts, Barbara J. Mulder, Ilja Blok, Lidia Tomkiewicz-Pająk, Kamil Szostek, Michele D’Alto, Giancarlo Scognamiglio, Katja Prokšelj, Gerhard-Paul Diller, Konstantinos Dimopoulos, Stephen J. Wort, Michael A. Gatzoulis
Journal: Circulation (2016)

Eisenmenger syndrome is associated with substantial morbidity and mortality. There is no consensus, however, on mortality risk stratification. We aimed to investigate survival and predictors of death in a large, contemporary cohort of Eisenmenger syndrome patients.In a multicenter approach, we identified adults with Eisenmenger syndrome under follow-up between 2000 and 2015. We examined survival and its association with clinical, electrocardiographic, echocardiographic, and laboratory parameters.We studied 1098 patients (median age, 34.4 years; range, 16.1-84.4 years; 65.1% female; 31.9% with Down syndrome). The majority had a posttricuspid defect (n=643, 58.6%), followed by patients with a complex (n=315, 28.7%) and pretricuspid lesion (n=140, 12.7%). Over a median follow-up of 3.1 years (interquartile range, 1.4-5.9), allowing for 4361.6 patient-years observation, 278 patients died and 6 underwent transplantation. Twelve parameters emerged as significant predictors of death on univariable analysis. On multivariable Cox regression analysis, only age (hazard ratio [HR], 1.41/10 years; 95% confidence interval [CI], 1.24-1.59; P<0.001), pretricuspid shunt (HR, 1.56; 95% CI, 1.02-2.39; P=0.041), oxygen saturation at rest (HR, 0.53/10%; 95% CI, 0.43-0.65; P<0.001), presence of sinus rhythm (HR, 0.53; 95% CI, 0.32-0.88; P=0.013), and presence of pericardial effusion (HR, 2.41; 95% CI, 1.59-3.66; P<0.001) remained significant predictors of death.There is significant premature mortality among contemporary adults with Eisenmenger syndrome. We report, herewith, a multivariable mortality risk stratification model based on 5 simple, noninvasive predictors of death in this population.
Impact of Comorbidity In Event-Free Survival, Toxicity and Adherence to Treatment In Chronic Myeloid Leukemia Patients Treated with Imatinib
Authors: Laura Fogliatto, Marcelo Capra, Mariza Schaan, Katia Fassina, Mario Sérgio Fernandes, Marco Antônio Schilling, Denise Almeida, Moema Nene, Tânia Hellwig, Gilca Nachtigal, Adriana Zardo João, Andréia Dias Almeida, Tito Vanelli Costa, Erica Lammerhirt Ottoni, Christina G S Fraga, Liane Esteves Daudt, Lucia Silla
Journal: Blood (2010)
Early Mortality in a Multinational Systemic Sclerosis Inception Cohort
Authors: Yanjie Hao, Marie Hudson, Murray Baron, Patricia Carreira, Wendy Stevens, Candice Rabusa, Solene Tatibouet, Loreto Carmona, Beatriz E. Joven, Molla Huq, Susanna Proudman, Mandana Nikpour
Journal: Arthritis & Rheumatology (2016)

Objective To determine mortality and causes of death in a multinational inception cohort of subjects with systemic sclerosis (SSc). Methods We quantified mortality as standardized mortality ratio (SMR), years of life lost, and percentage mortality in the first decade of disease. The inception cohort comprised subjects recruited within 4 years of disease onset. For comparison, we used a prevalent cohort, which included all subjects irrespective of disease duration at recruitment. We determined a single primary cause of death (SSc related or non–SSc related) using a standardized case report form, and we evaluated predictors of mortality using multivariable Cox regression. Results In the inception cohort of 1,070 subjects, there were 140 deaths (13%) over a median follow‐up of 3.0 years (interquartile range 1.0–5.1 years), with a pooled SMR of 4.06 (95% confidence interval [95% CI] 3.39–4.85), up to 22.4 years of life lost in women and up to 26.0 years of life lost in men, and mortality in the diffuse disease subtype of 24.2% at 8 years. In the prevalent cohort of 3,218 subjects, the pooled SMR was lower at 3.39 (95% CI 3.06–3.71). In the inception cohort, 62.1% of the primary causes of death were SSc related. Malignancy, sepsis, cerebrovascular disease, and ischemic heart disease were the most common non–SSc‐related causes of death. Predictors of early mortality included male sex, older age at disease onset, diffuse disease subtype, pulmonary arterial hypertension, and renal crisis. Conclusion Early mortality in SSc is substantial, and prevalent cohorts underestimate mortality in SSc by failing to capture early deaths, particularly in men and those with diffuse disease.
SGN-40 (Anti-huCD40 mAb) Monotherapy Induces Durable Objective Responses in Patients with Relapsed Aggressive Non-Hodgkin’s Lymphoma: Evidence of Antitumor Activity from a Phase I Study.
Authors: Ranjana Advani, Andres Forero-Torres, Richard R. Furman, Joseph D. Rosenblatt, Anas Younes, Brooke Shankles, Kate Harrop, Jonathan G. Drachman
Journal: Blood (2006)
Potent Strategy for Treatmet of Gvhd and Autoimmune-Diseased by Infusion of Donor-Typed or Even Third-Party Tolerogenic Dendritic Cells by Psoralen Plus UVA Treatment
Authors: Hideaki Maeba, Ryosei Nishimura, Rie Kuroda, Raita Araki, Shintaro Mase, Yasuhiro Ikawa, Akihiro Yachie, Shoichi Koizumi
Journal: Blood (2010)
Non-coding single nucleotide variants affecting estrogen receptor binding and activity
Authors: Amir Bahreini, Kevin Levine, Lucas Santana-Santos, Panayiotis V. Benos, Peilu Wang, Courtney Andersen, Steffi Oesterreich, Adrian V. Lee
Journal: Genome Medicine (2016)

Estrogen receptor (ER) activity is critical for the development and progression of the majority of breast cancers. It is known that ER is differentially bound to DNA leading to transcriptomic and phenotypic changes in different breast cancer models. We investigated whether single nucleotide variants (SNVs) in ER binding sites (regSNVs) contribute to ER action through changes in the ER cistrome, thereby affecting disease progression. Here we developed a computational pipeline to identify SNVs in ER binding sites using chromatin immunoprecipitation sequencing (ChIP-seq) data from ER+ breast cancer models. ER ChIP-seq data were downloaded from the Gene Expression Omnibus (GEO). GATK pipeline was used to identify SNVs and the MACS algorithm was employed to call DNA-binding sites. Determination of the potential effect of a given SNV in a binding site was inferred using reimplementation of the is-rSNP algorithm. The Cancer Genome Atlas (TCGA) data were integrated to correlate the regSNVs and gene expression in breast tumors. ChIP and luciferase assays were used to assess the allele-specific binding. Analysis of ER ChIP-seq data from MCF7 cells identified an intronic SNV in the IGF1R gene, rs62022087, predicted to increase ER binding. Functional studies confirmed that ER binds preferentially to rs62022087 versus the wild-type allele. By integrating 43 ER ChIP-seq datasets, multi-omics, and clinical data, we identified 17 regSNVs associated with altered expression of adjacent genes in ER+ disease. Of these, the top candidate was in the promoter of the GSTM1 gene and was associated with higher expression of GSTM1 in breast tumors. Survival analysis of patients with ER+ tumors revealed that higher expression of GSTM1, responsible for detoxifying carcinogens, was correlated with better outcome. In conclusion, we have developed a computational approach that is capable of identifying putative regSNVs in ER ChIP-binding sites. These non-coding variants could potentially regulate target genes and may contribute to clinical prognosis in breast cancer.
Incidental diagnosis of pancreatic neuroendocrine tumors.
Authors: A. Cheema, L. K. Kvols, J. R. Strosberg
Journal: Journal of Clinical Oncology (2011)

190 Background: Pancreatic neuroendocrine tumors are often discovered incidentally during radiologic or endoscopic examinations. The incidence of incidental detection is unknown. It is also unclear whether patients with incidentally discovered, asymptomatic tumors should be treated similarly to patients who present with tumor-related symptoms. Methods: A database of 425 patients with pancreatic neuroendocrine tumors treated at the H. Lee Moffitt Cancer Center was developed. Patient charts were reviewed to assess whether their diagnosis was incidental or prompted by tumor-related symptoms such as pain, jaundice, or neuroendocrine hormone secretion. The frequency of “incidentalomas” was categorized by TNM stage (AJCC, 7th edition). Overall survival was stratified by “incidental” versus “symptomatic” diagnosis. Results: Among 425 patients with histologically proven pancreatic neuroendocrine tumors, 112 patients (26%) had tumors that were discovered incidentally. The majority of stage I tumors (55%) were incidentally discovered. Among patients with stage IV tumors, 20% were detected incidentally (Table). Median survival of patients with incidentally discovered tumors was 103 months versus 84 months in patients who were symptomatic at diagnosis. Conclusions: A sizeable fraction of patients with pancreatic neuroendocrine tumors are diagnosed incidentally during evaluations for other conditions or unrelated symptoms. The majority of patients with stage I tumors are incidentally diagnosed. The increased incidence of pancreatic neuroendocrine “incidentaloms” may be contributing to improving survival rates in this disease. This study highlights the necessity of developing guidelines for management of patients with incidentally discovered, early-stage tumors. [Table: see text] No significant financial relationships to disclose.
Abstract 3895: Genomic alterations modify ubiquitination pathways in pulmonary carcinoid tumors
Authors: Michael K. Asiedu, Charles L. Thomas, Jie Dong, Prasidda Khadka, Zhifu Sun, Farhad Kosari, Jin Jen, Julian Molina, George Vasmatzis, Marie Christine Aubry, Ping Yang, Dennis Wigle
Journal: Cancer Research (2015)

Abstract Introduction: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, and comprise 30% of all carcinoid malignancies. They are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors, and are characterized by neuroendocrine differentiation and the potential to metastasize. Method: We characterized genomic alterations in pulmonary carcinoid tumors using whole genome and exome sequencing in addition to mRNA expression and SNP genotyping from specimens of normal lung, typical and atypical carcinoid, and SCLC. Results: Analysis of the sequencing data identified novel mutations in the pulmonary neuroendocrine tumor spectrum, including KRAS, ABCA9, GALNT10, HSFX1, PTHLH, RANBP2, BRIP1, FXR1, BACE2, NCOR2, DGKI, HERC1, HERC5 and GLI3. Pathway analysis found 45% of the cases to harbor a mutation in genes that are involved in protein-protein interaction with ubiquitin c (UBC) and may therefore play a role in ubiquitin protein degradation pathway. We also identified genes differentially expressed in corresponding regions of copy number variation, 52 of which were linked to ubiquitination pathways in 88% of the samples genotyped. Genes amplified in 15 to 23% of the cases included ITM2A, MAOA, EGR2, HAGH, TSC22D3, NBEA, TCEAL2, and TSPYL2 whereas deleted regions in 15% of the cases implicated CFD, GDI1, IFITM1 and IFITM2. Conclusion: These results suggest that in addition to previously identified pathways, dysregulation of the ubiquitin pathway may contribute to lung carcinoid tumorigenesis and could be exploited for therapeutic purposes. Citation Format: Michael K. Asiedu, Charles L. Thomas, Jie Dong, Prasidda Khadka, Zhifu Sun, Farhad Kosari, Jin Jen, Julian Molina, George Vasmatzis, Marie Christine Aubry, Ping Yang, Dennis Wigle. Genomic alterations modify ubiquitination pathways in pulmonary carcinoid tumors. [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 3895. doi:10.1158/1538-7445.AM2015-3895
293. Discovery of an Essential Receptor for Adeno-Associated Virus Infection
Authors: Sirika Pillay, Nancy L. Meyer, Andreas S. Puschnik, Omar Davulco, Jonathan Diep, Yoshi Ishikawa, Lucas T. Jae, Jonathan E. Wosen, Claude M. Nagamine, Michael S. Chapman, Jan E. Carette
Journal: Molecular Therapy (2016)

Cellular entry of adeno-associated viruses (AAV) is poorly understood, despite the prominent use of AAV vectors in gene therapy for several monogenic diseases. Using an unbiased, haploid genetic screen, we identified critical players in AAV serotype 2 (AAV2) entry including members of distinct protein complexes involved in retrograde trafficking as well as genes involved in the biosynthesis of the AAV2 attachment factor, heparan sulphate. We focused on the single most significantly enriched gene of the screen, an uncharacterized type-I transmembrane protein. Based on the evidence below we renamed this gene AAV receptor (AAVR). We discovered AAVR as capable of rapidly endocytosing from the plasma membrane and trafficking to the trans-Golgi network, taking a similar path as AAV particles utilize. Genetic ablation of AAVR using CRISPR/Cas9 technology demonstrated a robust resistance to AAV2 infection in a wide range of mammalian cell types, which could be reversed upon AAVR complementation. This confirmed the essentiality of AAVR in AAV2 infection. Further investigation revealed that AAVR was also required for the infections of all tested human and simian-derived AAV serotypes including AAV1, 3B, 5, 6, 8 and 9. Deeper characterization of AAVR showed it to contain Ig-like domains, which are commonly found in many virus receptors including those for poliovirus and measles. We observed that these domains are capable of binding to AAV2 particles, and anti-AAVR antibodies efficiently block AAV2 infection. Moreover, the importance of AAVR for AAV infection in vivo was demonstrated by the strong resistance of AAVR−/− mice to AAV9 infection, recapitulating what we showed in vitro. Collectively, the data indicates that AAVR is a universal receptor involved in AAV infection. This has significant implications for the improvement of future AAV vector design.
In prostate cancer, urinary and sexual function were worse with prostatectomy than active monitoring or radiotherapy
Authors: Philipp Dahm, Timothy Wilt
Journal: Annals of Internal Medicine (2016)

Source Citation Donovan JL, Hamdy FC, Lane JA, et al.; ProtecT Study Group. Patient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer. N Engl J Med. 2016;375:1425-37. 27626365
Therapeutic Effects of ALT-803, an IL-15 Superagonist, in Combination with Anti-CD20 Chimeric Antigen Receptor Modified Expanded Natural Killer CELLS Against Pediatric Burkitt Lymphoma (BL)
Authors: Yaya Chu, Fangyu Lee, Janet Ayello, Brian Hang, Melanie Zhang, Hing C. Wong, Dean A Lee, Mitchell S. Cairo
Journal: Blood (2015)
Different Adverse Event Profiles and Significant Hematological Improvement Are Noted When Deferasirox Was Used in Adult Patients with Chronic Transfusion-Related Iron Overload in Taiwan: Results from a Prospective Observational Clinical Trial
Authors: Bor-Sheng Ko, Ming-Chih Chang, Tzeon-Jye Chiou, Te-Kau Chang, Yeu-Chin Chen, Sheng-Fung Lin, Cheng-Shyong Chang, Yin-Che Lu, Su-Peng Yeh, Tsai-Yun Chen, Wei-Yu Chen
Journal: Blood (2015)
Pancreas Divisum Increases the Risk of Idiopathic Recurrent Acute Pancreatitis in the Presence of Cathepsin B L26V polymorphism
Authors: Mohsin Aslam, Steffie Avanthi, Vishnubhotla Ravikanth, Duvvuru Nageshwar Reddy, Rupjyoti Talukdar
Journal: Clinical Gastroenterology and Hepatology (2016)
High-Dose Therapy and Autologous Stem Cell Transplantation for Chemoresistant Diffuse Large B Cell Lymphoma: The Seattle Experience.
Authors: Jonathan A. Gutman, Ted A. Gooley, Jacob Nourigat, John M. Pagel, Oliver W. Press, Leona A. Holmberg, William I. Bensinger, Stephen H. Petersdorf, Ajay K. Gopal
Journal: Blood (2007)
Patients Treated with Rituximab-Containing Immunochemotherapy Have a Significant and Prolonged Lack of Humoral Response to Influenza Vaccine Associated with a Persistent Depletion of B Memory Cells.
Authors: Davide Bedognetti, Gabriele Zoppoli, Carlotta Massucco, Simonetta Zupo, Mario Roberto Sertoli, Manlio Ferrarini, Elisa Zanardi, Nicoletta Provinciali, Guido Siffredi, Graziano Caltabiano, Riccardo Ghio, Alessio Nencioni, Marco Messina, Omar Racchi, Andrea Bruzzone, Marianna Sabatino, Francesco M. Marincola, Maria Libera Ascierto, Lorenzo Uccellini, Pos Zoltan, Filippo Ansaldi, Andrea De Maria
Journal: Blood (2009)
Abstract 157: LncRNA ANRIL indicates a potential prognostic biomarker in gastric cancer and promotes tumor growth by silencing of miR-99a/miR-449a
Authors: Zhi Xu, Jinfei Chen, John M. Luk, Wei De
Journal: Cancer Research (2015)

Abstract Long noncoding RNAs are involved in several kinds of cancers. Here, we reported that ANRIL (CDKN2B-AS1), a 3.8-kb long noncoding RNA, recruiting and binding to PRC2, was generally upregulated in human gastric cancer (GC) tissues. In a cohort of 120 GC patients, the higher expression of ANRIL was significantly correlated with higher TNM stages (P = 0.041) and larger tumor sizes (P = 0.001). Multivariate analyses revealed that ANRIL expression served as an independent predictor for overall survival (OS) (P = 0.036). Further experiments revealed that the knockdown of ANRIL significantly repressed the proliferation of GC cell lines both in vitro and in vivo. We also showed that E2F1 could induce ANRIL and ANRIL-mediated growth promotion is partly due to epigenetic repression of miR-99a/miR-449a in Trans (controlling the targets_mTOR and CDK6/E2F1 pathway) by binding to PRC2, thus forming a positive feedback loop, continuing to promote GC cell proliferation. To our knowledge, this is the first report which showed that the role of ANRIL in the progression of GC and ANRIL could crosstalk with microRNAs in epigenetic level. Our results suggest that ANRIL, as a growth regulator, may serve as a potential prognostic biomarker and target for new therapies in human GC. Citation Format: Zhi Xu, Jinfei Chen, John M. Luk, Wei De. LncRNA ANRIL indicates a potential prognostic biomarker in gastric cancer and promotes tumor growth by silencing of miR-99a/miR-449a. [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 157. doi:10.1158/1538-7445.AM2015-157
A comparative effectiveness trial of two faecal immunochemical tests for haemoglobin (FIT). Assessment of test performance and adherence in a single round of a population-based screening programme for colorectal cancer
Authors: Basilio Passamonti, Morena Malaspina, Callum G Fraser, Beatrice Tintori, Angela Carlani, Valentina D'Angelo, Paola Galeazzi, Eugenio Di Dato, Loretta Mariotti, Simonetta Bulletti, Maria Rosaria D'Amico, Daniela Gustinucci, Nadia Martinelli, Nicoletta Spita, Elena Cesarini, Tiziana Rubeca, Mariadonata Giaimo, Nereo Segnan, Carlo Senore
Journal: Gut (2016)

Aim To compare acceptability and diagnostic accuracy of a recently available faecal immunochemical test (FIT) system (HM-JACKarc) with the FIT routinely used in an established screening programme (OC-Sensor). Design Randomised controlled trial ( ISRCTN20086618 ) within a population-based colorectal cancer (CRC) screening programme. Subjects eligible for invitation in the Umbria Region (Italy) programme were randomised (ratio 1:1) to be screened using one of the FIT systems. Results Screening uptake among the 48 888 invitees was the same for both systems among subjects invited in the first round and higher with OC-Sensor than with HM-JACKarc (relative risk (RR): 1.03; 95% CI 1.02 to 1.04) among those invited in subsequent rounds. Positivity rate (PR) was similar with OC-Sensor (6.5%) as with HM-JACKarc (6.2%) among subjects performing their first FIT screening and higher with OC-Sensor (5.6%, RR: 1.25, 95% CI 1.12 to 1.40) than with HM-JACKarc (4.4%) among those screened in previous rounds. Positive predictive value (PPV) (OC-Sensor: 25.9%, HM-JACKarc: 25.6%) and detection rate (DR) (OC-Sensor: 1.40%; HM-JACKarc: 1.42%) for advanced neoplasia (AN: CRC + advanced adenoma) were similar among subjects performing their first FIT screening. The differences in the AN PPV (OC-Sensor: 20.3%, HM-JACKarc: 22.6%) and DR (OC-Sensor: 0.96%, HM-JACKarc: 0.83%) among those screened in previous rounds were not statistically significant. The number needed to scope to detect one AN was 3.9 (95% CI 5.8 to 2.9) and 3.9 (95% CI 5.5 to 2.9) at first and 4.9 (95% CI 5.8 to 4.2) and 4.4 (95% CI 5.3 to 3.7) at subsequent screening, with OC-Sensor and HM-JACKarc, respectively. Conclusions Our results suggest that acceptability and diagnostic performance of HM-JACKarc and of OC-Sensor systems are similar in a screening setting. Trial registration number ISRCTN20086618 ; Results.