tbuckley/cabot-search huggingface dataset:
Abstract 1110: Inhibition of histone deacetylase induces miR-320-mediated androgen receptor suppression in prostate cancer
Authors: Shinya Sato, Keisuke Katsushima, Keiko Shinjo, Satoru Takahashi, Yutaka Kondo
Journal: Cancer Research (2016)

Abstract Targeting androgen receptor (AR) by pharmacological intervention is one of the effective approaches for treatment of malignant prostate cancers. Histone deacetylase (HDAC) alters epigenetic status of tumor-associated genes, including microRNAs (miRNAs), and affects the behavior of cancers. Here we examined molecular effects of a HDAC inhibitor, OBP-801, on AR expression and tumor cell growth in prostate cancers. Treatment of OBP-801 efficiently suppressed cell growth of three prostate cancer lines (22Rv1, VCaP, and LNCaP), together with AR downregulation, regardless of their hormone sensitivity. Intriguingly, this effect by OBP-801 is not due to downregulation of transcriptional activity of the AR gene, but due to post-transcriptional regulation, namely miRNA-mediated suppression. Among the upregulated miRNAs after OBP-801 treatment in three prostate cancer cell lines, miR-320a, of which expression was significantly correlated with prognosis of prostate cancers (P = 0.0185), was the most closely associated with AR expression. miR-320a mimic suppressed AR protein expression together with growth suppression, while anti-miR320a significantly abrogated the growth suppression by OBP-801 treatment. Fluorescent in situ hybridization analysis revealed that miR-320a was highly expressed in human normal prostate luminal cells but rarely expressed in prostate cancer cells. In AR-dependent prostate tumorigenic rat model, OBP-801 treatment profoundly increased the miR-320 expression and repressed prostate tumorigenesis. Our data demonstrated that OBP-801 effectively suppressed AR activity via epigenetic upregulation of miR-320a, which resulted in tumor cell growth suppression of prostate cancers. OBP-801 may be a potent drug as an AR targeting therapy in AR positive prostate cancer regardless of androgen dependency. Citation Format: Shinya Sato, Keisuke Katsushima, Keiko Shinjo, Satoru Takahashi, Yutaka Kondo. Inhibition of histone deacetylase induces miR-320-mediated androgen receptor suppression in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1110.
Prevalence, Clone Size and Lineage Diversity Of HLA-A Allele-Lacking Leukocytes In Patients With Acquired Aplastic Anemia
Authors: Hiroyuki Maruyama, Takamasa Katagiri, Yoshitaka Zaimoku, Chizuru Saito, Kohei Hosokawa, Hirohito Yamazaki, Seishi Ogawa, Shinji Nakao
Journal: Blood (2013)
Abstract 4936: The function role of Brf1 in alcohol-induced human and mouse hepatocellular carcinoma*
Authors: Shuping Zhong
Journal: Cancer Research (2016)

Abstract Brf1 (TFIIB-related factor 1) specifically regulates the transcription of Pol III genes (RNA polymerase III-dependent genes), including tRNAs and 5S rRNAs, which are elevated in both transformed and tumor cells, suggesting that they play a crucial role in tumorigenesis. Our recent studies have demonstrated that alcohol consumption increases Brf1 expression and Pol III gene transcription to promote tumor development. However, it remains to be investigated that Brf1 is expressed in human cancers. At the present studies, we have determined the significance of Brf1 overexpression in human hepatocellular carcinoma (HCC) and the impaction of repressing Brf1 expression in alcohol-promoted cell transformation. Biopsies of human HCC, liver tumor samples of mice and cell lines of normal and tumor liver were utilized to determine alteration of Brf1 expression using cytological and molecular biological approaches. The result indicates that Brf1 expression is increased in human cases of HCC. High expression of Brf1 displays shorter overall survival period. Levels of Brf1 and Pol III gene transcription in HCC patients with alcohol consumption show an additional increase, compared with the cases of non-HCC with or without alcohol intake. Induction of Brf1 and Pol III genes by ethanol in hepatoma cells is higher than in non-tumor cells. Ethanol increases the rate of cell transformation. Repression of Brf1 inhibits alcohol-promoted cell transformation. Together, these studies demonstrate that Brf1 is overexpressed in HCC cases and liver tumor cell lines. High level of Brf1 in human HCC is correlated with short survival time. Alcohol consumption enhances Brf1 expression to promote cell transformation. Brf1 is a new biomarker of diagnosis and prognosis of HCC. *: The project is supported by NIH grants: AA017288, AA021114 and AA02324 to Shuping Zhong Citation Format: Shuping Zhong. The function role of Brf1 in alcohol-induced human and mouse hepatocellular carcinoma*. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4936.
Abstract 2927: miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cell
Authors: Mads H. Rasmussen, Iben Lyskjær, Rosa R. Jersie-Christensen, Line S. Tarpgaard, Bjarke Primdal-Bengtson, Morten M. Nielsen, Jakob S. Pedersen, Tine P. Hansen, Flemming Hansen, Jesper V. Olsen, Per Pfeiffer, Torben F. Ørntoft, Claus L. Andersen
Journal: Cancer Research (2016)

Abstract Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major medical problem, and predictive markers are urgently needed. Recently, miR-625-3p was reported as a promising predictive marker. Here, we have used in vitro models to show that miR-625-3p functionally induces oxPt resistance in CRC cells, and have identified signalling networks affected by mir-625-3p. The p38 MAPK activator MAP2K6 was shown to be a direct target of miR-625-3p, and, accordingly, was downregulated in patients not responding to oxPt therapy. miR-625-3p resistance could be reversed in CRC cells by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. In addition, by reducing p38 MAPK signalling using either siRNA technology, chemical inhibitors to p38 or by ectopic expression of dominant negative MAP2K6 protein we induced resistance to oxPt. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signalling as a possible driving force behind oxPt resistance. Our study shows that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks, and corroborates the predictive power of miR-625-3p. Citation Format: Mads H. Rasmussen, Iben Lyskjær, Rosa R. Jersie-Christensen, Line S. Tarpgaard, Bjarke Primdal-Bengtson, Morten M. Nielsen, Jakob S. Pedersen, Tine P. Hansen, Flemming Hansen, Jesper V. Olsen, Per Pfeiffer, Torben F. Ørntoft, Claus L. Andersen. miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cell. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2927.
Tailored Therapist-Guided Internet-Based Cognitive Behavioral Treatment for Psoriasis: A Randomized Controlled Trial
Authors: Sylvia van Beugen, Maaike Ferwerda, Saskia Spillekom-van Koulil, Jurgen V. Smit, Manon E.J. Zeeuwen-Franssen, Elisabeth B.M. Kroft, Elke M.G.J. de Jong, Marisol E. Otero, A. Rogier T. Donders, Peter C.M. van de Kerkhof, Henriët van Middendorp, Andrea W.M. Evers
Journal: Psychotherapy and Psychosomatics (2016)

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; Patients with somatic conditions, such as psoriasis, frequently suffer from high burden of their disease in daily life and might benefit from internet-based cognitive behavioral therapy (ICBT) tailored to their adjustment problems. The aim of this multicenter randomized controlled trial was to examine the effects of therapist-guided, individually tailored ICBT in a clinical sample of patients with psoriasis. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A total of 131 patients with psoriasis, who were screened for a psychological risk profile, were randomized to either care as usual (CAU, n = 66) or ICBT in addition to CAU (n = 65). Participants filled out standardized self-report questionnaires assessing physical and psychological functioning and impact on daily activities at baseline, posttreatment assessment, and 6-month follow-up. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In covariate-controlled linear mixed-model analyses, significantly larger improvements in ICBT compared to CAU were found in the primary outcomes physical functioning (p = 0.03, d = 0.36) and impact on daily activities (p = 0.04, d = 0.35), but not in psychological functioning (p = 0.32), up to 6 months after treatment compared to baseline. In explorative analyses, the working alliance measured at the beginning of ICBT treatment predicted improved physical (p = 0.02) and psychological (p &lt; 0.001) outcomes. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Results underline the promise of therapist-guided, individually tailored ICBT to improve physical functioning and reduce the impact of psoriasis on daily activities in patients with a psychological risk profile. Establishing a good therapeutic relationship early on may be an important factor that influences treatment outcomes in personalized ICBT interventions. Further research is needed to evaluate ICBT effectiveness in additional samples and to explore its underlying mechanisms.
Changes in Functional Mobility and Musculoskeletal Pain After Bariatric Surgery in Teens With Severe Obesity
Authors: Justin R. Ryder, Nicholas M. Edwards, Resmi Gupta, Jane Khoury, Todd M. Jenkins, Sharon Bout-Tabaku, Marc P. Michalsky, Carroll M. Harmon, Thomas H. Inge, Aaron S. Kelly
Journal: JAMA Pediatrics (2016)

<h3>Importance</h3> Severe obesity is associated with mobility limitations and higher incidence of multijoint musculoskeletal pain. It is unknown whether substantial weight loss improves these important outcomes in adolescents with severe obesity. <h3>Objective</h3> To examine the association of bariatric surgery with functional mobility and musculoskeletal pain in adolescents with severe obesity up to 2 years after surgery. <h3>Design, Setting, and Participants</h3> The Teen<b>–</b>Longitudinal Assessment of Bariatric Surgery Study is a prospective, multicenter, observational study, which enrolled 242 adolescents (≤19 years of age) who were undergoing bariatric surgery from March 2007 through February 2012 at 5 US adolescent bariatric surgery centers. This analysis was conducted in November 2015. <h3>Interventions</h3> Roux-en-Y gastric bypass (n = 161), sleeve gastrectomy (n = 67), or laparoscopic adjustable gastric band (n = 14). <h3>Main Outcomes and Measures</h3> Participants completed a 400-m walk test prior to bariatric surgery (n = 206) and at 6 months (n = 195), 12 months (n = 176), and 24 months (n = 149) after surgery. Time to completion, resting heart rate (HR), immediate posttest HR, and HR difference (resting HR minus posttest HR) were measured and musculoskeletal pain concerns, during and after the test, were documented. Data were adjusted for age, sex, race/ethnicity, baseline body mass index (calculated as weight in kilograms divided by height in meters squared), and surgical center (posttest HR and HR difference were further adjusted for changes in time to completion). <h3>Results</h3> Of the 206 adolescents with severe obesity included in the study, 156 were female (75.7%), the mean (SD) age was 17.1 (1.6) years, and the mean (SD) body mass index was 51.7 (8.5). Compared with baseline, significant improvements were observed at 6 months for the walk test time to completion (mean, 376 seconds; 95% CI, 365-388 to 347 seconds; 95% CI, 340-358;<i>P</i> &lt; .01), resting HR (mean, 84 beats per minute [bpm]; 95% CI, 82-86 to 74 bpm; 95% CI, 72-76), posttest HR (mean, 128 bpm; 95% CI, 125-131 to 113 bpm; 95% CI, 110-116), and HR difference (mean, 40 bpm; 95% CI, 36-42 to 34 bpm; 95% CI, 31-37). These changes in time to completion, resting HR, and HR difference persisted at 12 months and 24 months. Posttest HR further improved from 6 months to 12 months (mean, 113 bpm; 95% CI, 110-116 to 108 bpm; 95% CI, 105-111). There were statistically significant reductions in musculoskeletal pain concerns at all points. <h3>Conclusions and Relevance</h3> These data provide evidence that bariatric surgery in adolescents with severe obesity is associated with significant improvement in functional mobility and in the reduction of walking-related musculoskeletal pain up to 2 years after surgery.
A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab
Authors: Primal Kaur, Vincent Chow, Nan Zhang, Michael Moxness, Arunan Kaliyaperumal, Richard Markus
Journal: Annals of the Rheumatic Diseases (2016)

To demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501.
Abstract 172: Managing metastatic breast cancer via serial monitoring with circulating cell-free tumor DNA next generation sequencing testing
Authors: Laura Austin, Rebecca Nagy, Oliver Zill, Richard B. Lanman, AmirAli Talasaz, Massimo Cristofanilli
Journal: Cancer Research (2016)

Abstract Background: Metastatic breast cancer (MBC) is an incurable disease with complex molecular features including somatic mutations that evolve in relation to genomic instability and selective treatment pressure. Patients with treatment-refractory MBC may benefit from tumor genomic evaluation using next generation sequencing (NGS). Furthermore, analysis of circulating tumor DNA (ctDNA) in patients with advanced disease offers the possibility of non-invasive molecular monitoring. Methods: A patient with MBC was tested at each progression with a ctDNA NGS panel (Guardant360™) that includes all NCCN-recommended somatic genomic variants for solid tumors and sequences complete exons of &amp;gt;50 genes to report single nucleotide variants (SNVs), fusions, amplifications, and indels with high sensitivity and ultra-high specificity (&amp;gt;99.9999%). The patient was diagnosed with invasive breast cancer at age 44 and treated with surgery and hormonal therapy. At age 61, she had axillary adenopathy and liver metastases. Treatment details are in Table 1. Results: ctDNA analysis was performed at the time of metastatic diagnosis and at 5 additional time points over the course of treatment. All samples revealed an ERBB2 exon 19 indel (p.Leu755_Glu757delinsSer), and multiple SNVs and gene amplifications. ERBB2 amplification was seen in 4 of 6 samples. Mutant allele fractions (Table 1) correlated with clinical response to treatment and progression. Conclusions: Analysis of ctDNA in this patient identified an ERBB2 exon 19 indel, which are present in 2-4% of non-small cell lung cancers but 1-2% in breast cancer. Treatment with anti-HER2 monoclonal antibody or dual anti-EGFR/ERBB2 tyrosine kinase inhibitor therapies may show clinical benefit. ctDNA analysis can detect emergence of actionable resistance mutations with the advantage of serial evaluation, allowing capture of inter- and intra-tumor heterogeneity and illustration of molecular progression and response. Table 1.Blood DrawDisease status at time of blood drawMutant allele fraction of ERBB2 indel (* = ERBB2 amplification)Treatment1Initial diagnosis9%trastuzumab, pertuzumab and docetaxel (TPD), cycle 12Stable disease1%*TPD cycle 23Progressing10%*TPD cycle 34Progressing62%*trastuzumab, emtansine (TDM1) 3 cycles5Progressing70%*vinorelbine, trastuzumab, everolimus6Partial response1%flourouracil, epirubicin, cyclophoasphamide Citation Format: Laura Austin, Rebecca Nagy, Oliver Zill, Richard B. Lanman, AmirAli Talasaz, Massimo Cristofanilli. Managing metastatic breast cancer via serial monitoring with circulating cell-free tumor DNA next generation sequencing testing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 172.
459P Risk of pneumonitis in patients with advanced NSCLC treated with pembrolizumab in KEYNOTE-001
Authors: M.-J. Ahn, L. Gandhi, O. Hamid, M.D. Hellmann, E.B. Garon, S.S. Ramalingam, G.M. Lubiniecki, J. Zhang, B. Piperdi, R. Hui
Journal: Annals of Oncology (2015)
Multi-layered nanofibrous mucoadhesive films for buccal and sublingual administration of drug-delivery and vaccination nanoparticles - important step towards effective mucosal vaccines
Authors: Josef Mašek, Daniela Lubasová, Róbert Lukáč, Pavlína Turánek-Knotigová, Pavel Kulich, Jana Plocková, Eliška Mašková, Lubomír Procházka, Štěpán Koudelka, Nongnut Sasithorn, Jozsef Gombos, Eliška Bartheldyová, František Hubatka, Milan Raška, Andrew D. Miller, Jaroslav Turánek
Journal: Journal of Controlled Release (2016)
Abstract 667: Tumor cell dormancy is mediated by an increase in RTK signaling in reversible pancreatic cancer models expressing oncogenic K-Ras and c-Myc
Authors: Nirakar Rajbhandari
Journal: Cancer Research (2016)

Abstract Recent genetic studies of pancreatic cancer expressing mutant Kras and c-Myc strongly favor targeted therapies against these oncogenic drivers for the successful treatment of advanced staged pancreatic cancer. The potential limitation of these treatments is that they likely leave residual cancer cells that can play a role in tumor recurrence. Our study is focused on understanding the molecular mechanism of the survival of pancreatic cancer cells in the absence of the tumor-driving oncogene in order to successfully eliminate cancer cells and prevent tumor relapse. Using a reversible c-Myc-induced pancreatic cancer model, we have demonstrated that expression of c-Myc in pancreatic progenitors is sufficient to induce invasive pancreatic cancer, and its expression is required for the maintenance of tumors at primary and metastatic sites. However, despite the complete macroscopic remission of invasive pancreatic tumors at primary and metastatic sites upon downregulation of c-Myc, a few cancer cells survived and remained dormant for a protracted period of time (Lin et al., 2013). In this current study, we have used a reversible Kras-induced pancreatic tumor model and found that cancer cell dormancy is a common attribute in pancreatic cancer following oncogene ablation. In an effort to identify common, cancer cell-intrinsic molecular pathways that mediate residual disease following the ablation of oncogenic drivers, we performed a genome-wide gene expression analysis (RNA-Seq) of in vivo-derived bulk tumor cells and dormant cancer cells that survived the ablation of c-Myc and oncogenic Kras. Comparison of the gene expression profile of bulk and residual cancer cells revealed that the residual cancer cells have increased receptor tyrosine kinase (RTK)/Akt signaling as a common mechanism for their survival in both c-Myc and Kras-induced tumors. We have experimentally validated the importance of this signaling pathway in cancer cell survival in the absence of oncogenic signaling in both tumor models. In comparison to control mice, we observed a significant slow tumor growth and delayed tumor relapse resulting in longer survival of the tumor bearing mice though a combination of this RTK/Akt pathway inhibition and ablation of Kras or c-Myc. In conclusion, our current study in reversible cancer models highlights the importance for the development of an adjuvant therapeutic strategy targeting this RTK/Akt pathway in addition to oncogenic drivers to effectively eradicate residual cancer cells and to prevent pancreatic cancer recurrence. Citation Format: Nirakar Rajbhandari. Tumor cell dormancy is mediated by an increase in RTK signaling in reversible pancreatic cancer models expressing oncogenic K-Ras and c-Myc. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 667.
Characterization of Chorioretinopathy Associated with Mitochondrial Trifunctional Protein Disorders
Authors: Erin A. Boese, Nieraj Jain, Yali Jia, Catie L. Schlechter, Cary O. Harding, Simon S. Gao, Rachel C. Patel, David Huang, Richard G. Weleber, Melanie B. Gillingham, Mark E. Pennesi
Journal: Ophthalmology (2016)
Definitions for Sepsis and Septic Shock
Authors: Shivinder Singh, Sanil Mohan, Ravi Singhal
Journal: JAMA (2016)

To the Editor The Sepsis-3 definition of sepsis1 includes the SOFA score.2 The SOFA scoring system has stood the test of time as a simple, readily reproducible scoring system to monitor the progress of sepsis patients, and its place in clinical evaluation is undisputed.
Abstract 5081: hnRNP A18: an emerging novel target for cancer therapy
Authors: Palak R. Parekh, Elizabeth Chang, Qingyuan Yang, France Carrier
Journal: Cancer Research (2016)

Abstract Heterogenous ribonucleoprotein A18 (hnRNP A18) increases de novo protein translation during cellular stress. Although hnRNP A18 has recently been associated with several cancers, the exact role of it during the multifactorial process of cancer growth and progression is still unknown. Accordingly, we examined the dependability of various malignant cancer cell lines on hnRNP A18. Down-regulation of hnRNP A18 impaired the proliferative, invasive and migratory properties of melanoma and triple negative breast cancer cell lines in vitro, while overexpression of hnRNP 18 caused an increase in invasiveness. Consistent with these observations, we detected remarkable reduction of tumor growth in two mouse xenograft models, melanoma and breast cancer. Moreover, down-regulation of hnRNP A18 increased the sensitivity of melanoma cells and breast cancer cells to paclitaxel and 5-fluoro uracil, respectively. In conclusion, hnRNP A18 plays a key role in tumor growth and progression. It may serve as a novel target for the treatment of cancer. Citation Format: Palak R. Parekh, Elizabeth Chang, Qingyuan Yang, France Carrier. hnRNP A18: an emerging novel target for cancer therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5081.