tbuckley/cabot-search huggingface dataset:
Abstract 492: Epigenetic suppression of miRNA-203 promotes Ewing sarcoma malignancy
Authors: Tim Hensel, Esther Heid, Stephanie Plehm, Stefan Burdach, Günther H. Richter
Journal: Cancer Research (2015)

Abstract Ewing sarcoma (ES), a malignancy of bone and soft tissue that affects children and young adults, is characterized by early metastasis to lung and bone and by oncogenic ews/ets translocations. We previously observed the histone methyltransferase Enhancer of Zeste, Drosophila, Homolog 2 (EZH2) to be regulated by EWS-FLI1 and highly increased in ES. We hypothesized non-coding RNAs to contribute to epigenetic processes and malignancy of ES. Here we show by ChIP on chip analysis that EZH2 occupies promoter regions of putative tumor suppressor miRNAs, oncogenic miRNAs and differentiation-associated miRNAs in ES and investigated their functional relevance by miRNA mimic, RNA interference, and functional assays. We show that hsa-miR-203a-3p (miR-203), a promoter of epidermal differentiation and trigger to exit cell cycle, was found epigenetic silenced in ES. We not only observed miR-203 up-regulation in different ES lines after EZH2 knock down or treatment with the EZH2 inhibitors GSK126 but also after histone de-acetylase inhibition (HDACi) via Trichostatin A (TSA) as well as MS-275. Similarly, treatment of ES lines with the DNA-methylation inhibitor 5′-azacytidine resulted in a strong up-regulation of miR-203 in ES. On the other hand, de-regulated expression of miR-203 after transient transfection with a miR-203-mimic identified a feed back loop resulting in a down-regulation of EWS-FLI1 and EZH2 in ES cell lines as compared to controls. In functional assays we observed that an increased expression of miR-203 suppressed contact dependent as well as independent growth in ES. In addition, in vitro invasiveness was strongly impaired after over-expression of miR-203. Taken together, we demonstrate the essential need for epigenetic suppression of miR-203 expression in ES that otherwise would suppress critical features of ES malignancy such as contact independent growth and invasiveness of ES. These results further provide a rationale for epigenetic combination therapy directed to reverse miR-203 suppression. Citation Format: Tim Hensel, Esther Heid, Stephanie Plehm, Stefan Burdach, Günther H. Richter. Epigenetic suppression of miRNA-203 promotes Ewing sarcoma malignancy. [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 492. doi:10.1158/1538-7445.AM2015-492
Marketing Claims for Infant Formula
Authors: Helen K. Hughes, Michael M. Landa, Joshua M. Sharfstein
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Phase I Study of the Oral Histone Deacetylase Inhibitor SB939 In Patients with Advanced Hematologic Malignancies
Authors: Guillermo Garcia-Manero, Charles Chuah, George Wilding, Julie Chang, Srdan Verstovsek, Stefan Faderl, Hagop M. Kantarjian, Kantharaj Ethirajulu, Joy Zhu
Journal: Blood (2010)
Inflammatory Plasma Proteins Predict Disease Severity and Response to Therapy in Patients with LCH
Authors: Daniel Zinn, Howard Lin, Albert Shih, Brooks Scull, Miguel Dario Cantu, Harshal Abhyankar, Rikhia Chakraborty, Karen Phaik Har Lim, Tricia L. Peters, Sergio Lira, Chris Tsz-Kwong, Kenneth McClain, Miriam Merad, Carl Allen
Journal: Blood (2015)
Abstract 816: Persistent effects of radiation on intestinal stem cells: implications for colorectal carcinogenesis
Authors: Kamal Datta, Shubhankar Suman, Santosh Kumar, Albert J. Fornace
Journal: Cancer Research (2015)

Abstract Adult stem cells, similar to somatic cells, are also subject to a similar array of insults and are therefore presumed to accrue radiation damage. Unlike somatic cells, however, lesions arising in the stem cell compartment are propagated both to daughter stem cells and to downstream lineages through the processes of self-renewal and differentiation. The impact of damage accrued in individual stem cells can thus have major ramifications for all levels of the developmental hierarchy leading to cancer initiation and promotion in human as well as in animal models of human colorectal cancer (CRC) such as in APCMin/+. Differentiation of intestinal stem cell (ISC) and ordered migration of differentiated cells along crypt-villus axis is essential for maintenance of intestinal homeostasis and provides a model system to study stem cell alterations after radiation. Furthermore, considering that tumors in animal models of CRC almost exclusively develop in the small intestine and increased intestinal tumor frequency was radiation quality dependent, we investigated persistent effects of radiation quality on ISC as well as on differentiated intestinal epithelial cells in mice. Mice (6 to 8 week; C57BL/6J) were exposed to γ (0.5 and 2 Gy) and 56-Fe (0.5 and 1.6 Gy) radiation, samples were collected 7 d and 2 m after radiation exposure, and carcinogenic precursor events such as persistent oxidative stress and DNA damage were assessed. Higher persistently increased oxidative stress and oxidative DNA damage was observed after 56-Fe relative to γ radiation. However, increased oxidative stress did not increase cell death implying that the oxidative stress was sub-lethal. Autophagy, a self-cannibalistic process of cell involved in removing damaged cell and cell constituents, was consistently downregulated in a radiation quality dependent manner even 2 m after exposure suggesting persistence of damage-bearing cells. We believe radiation-induced autophagy downregulation and sub-lethal oxidative stress is working in tandem to trigger proliferative signaling such as PI3K/Akt and mTOR in intestinal cells. Taken together our results provide insight into radiation quality dependent persistent cancer-related molecular events, which could have altered phenotypic behavior of ISC such as proliferation, differentiation, and migration. Note: This abstract was not presented at the meeting. Citation Format: Kamal Datta, Shubhankar Suman, Santosh Kumar, Albert J. Fornace. Persistent effects of radiation on intestinal stem cells: implications for colorectal carcinogenesis. [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 816. doi:10.1158/1538-7445.AM2015-816
Abstract 1961: Anti-endocrine therapy in breast cancerresistance can be circumvented by targeting ribonucleotide reductase M2 usingthe pharmaceutical agent Didox
Authors: Khyati N. Shah, Howard L. Elford, Jesika S. Faridi
Journal: Cancer Research (2015)

Abstract Breast Cancers (BC) that are sensitive to anti-endocrine therapies such as tamoxifen develop resistance despite their initial favorable response. To gain mechanistic insight on endocrine resistance, gene expression profiling was performed to determine the transcripts that are differentially expressed post-tamoxifen therapy under conditions of prolonged drug treatment and development of resistance. This resistance outcome is the result of the cancer cells invoking survival functions that are up-regulated leading to enhanced cell proliferation and cell motility networks. These networks were validated in a larger panel of breast cancer cells. Here, we report the activation of Growth factor signaling and IKK-βsignaling, NFκB signaling, in BC cells upon acquired resistance to ER blockade by anti-endocrine therapy. Moreover, ribonucleotide reductase (RRM2) was revealed as a key contributor to acquired tamoxifen resistance. An RNA interference screen demonstrated that suppression of RRM2 by the RR inhibitor Didox results in down-regulation of Her2 and EGFR, modulates ER-α signaling, alters NFκB activity and expression, and decreases anti-apoptotic pathways. Indeed, concomitant treatment of tamoxifen and Didox causes blockade of ER and RRM2 induced prolonged ER inhibition and severely impairs the growth of resistant tumor cells. Collectively, these results identify distinct mechanisms that mediate secondary resistance to anti-endocrine therapies, all of which reactivate RR signaling. These observations provide a rational strategy to overcome the multifaceted clonal heterogeneity that emerges when tumors are treated with targeted agents. We propose that Didox and an anti-hormonal therapy should be tested in BC patients who become refractory to anti-endocrine therapies. Citation Format: Khyati N. Shah, Howard L. Elford, Jesika S. Faridi. Anti-endocrine therapy in breast cancerresistance can be circumvented by targeting ribonucleotide reductase M2 usingthe pharmaceutical agent Didox. [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 1961. doi:10.1158/1538-7445.AM2015-1961
Evaluation of gene mutations beyond <i>KRAS</i> as predictive biomarkers of response to panitumumab in a randomized, phase III monotherapy study of metastatic colorectal cancer (mCRC).
Authors: K. Oliner, M. Peeters, S. Siena, E. Van Cutsem, J. Huang, Y. Humblet, J. Van Laethem, T. Andre, J. S. Wiezorek, S. D. Patterson
Journal: Journal of Clinical Oncology (2011)

3530 Background: KRAS mutation is an established biomarker for lack of response to antiepidermal growth factor receptor (EGFR) antibodies in mCRC. We used next generation sequencing to investigate whether mutation of other genes known to be altered in CRC predict response to panitumumab. Methods: Banked formalin fixed paraffin embedded patient tumor samples from a randomized, phase III monotherapy clinical trial that compared panitumumab + best supportive care (BSC) with BSC alone (the 408 study) were sequenced. After disease progression, patients randomized to the BSC alone arm could enroll in an optional panitumumab extension study (the 194 study). Tumor samples previously analyzed for KRAS codon 12 and 13 mutations were sequenced for mutations in 9 genes: AKT1, BRAF, CTNNB1, EGFR, KRAS (codon 61), NRAS, PIK3CA, PTEN, and TP53. This analysis presents pooled efficacy data from the 408 and 194 studies by genotype. Results: In the 408 study (multimarker data presented at AACR 2010), 463 patients were randomized to panitumumab + BSC (n = 231) or BSC alone (n = 232); 176 of these BSC alone patients enrolled in the 194 study. In total, 288 patients had multimarker data available; 257 of these were treated with panitumumab monotherapy on either study (147 from study 408 and 110 from study 194). In this treated population, 22/138 (15.9%) patients with wild type (WT) KRAS tumors compared with 0/103 (0%) with mutant (MT) KRAS (codons 12, 13) tumors had an objective response (OR). OR rates (ORR) for other single genotypes within the KRAS WT subset are shown (Table). Conclusions: Implications of tumor genotype at the 9 loci for clinical outcomes (ORR and progression free survival) with panitumumab and detailed results from the aggregate analysis of the 408 and 194 studies will be presented. Genotype N ORR (%) WT KRAS (codons 12, 13) WT KRAS (codon 61) 138 15.9 MT KRAS (codon 61) 6 16.7 WT KRAS (codons 12, 13, 61) WT AKT1 121 16.5 MT AKT1 1 0 WT BRAF 107 16.8 MT BRAF 13 0 WT CTNNB1 118 15.3 MT CTNNB1 2 50.0 WT EGFR 134 16.4 MT EGFR 0 Not applicable WT NRAS 126 17.5 MT NRAS 9 0 WT PIK3CA 117 14.5 MT PIK3CA 10 20.0 WT PTEN 122 16.4 MT PTEN 9 11.1 WT TP53 50 14.0 MT TP53 84 16.7
172. B-Type Natriuretic Peptide Gene Therapy as a Novel Early Treatment for Familial Hypertrophic Cardiomyopathy
Authors: Cassandra A. Bongers, Sara J. Holditch, Claire A. Schreiber, John P. Konhilas, John C. Burnett, Yasuhiro Ikeda
Journal: Molecular Therapy (2016)

Hypertrophic cardiomyopathy (HCM) is the most common familial cardiomyopathy, with the prevalence between 0.2 to 0.5%. HCM presents as an increase in left ventricular mass with thickening of the interventricular septum (IVS), myocellular disarray, interstitial fibrosis, heart rhythm abnormalities, and sudden death, necessitating therapeutic intervention. HCM is commonly caused by mutations in genes MYH7, MYBPC3, TNNT2, and TNNI3. The cardiac hormone, B-type natriuretic peptide (BNP) is a guanylyl cyclase A (GC-A) agonist. Physiological effects of BNP include natriuresis, vasodilation and blood pressure-lowering action. Additionally, BNP shows direct cardioprotective properties including anti-hypertrophic and anti-fibrotic effects, independently of its anti-hypertensive effects. We have recently found that genetic BNP ablation results in progressive cardiac hypertrophy with upregulation in HCM-associated genes in rats. In the current study, we tested the hypothesis that sustained BNP treatment with novel gene delivery of BNP may preserve cardiac function and structure in HCM in a mouse model of HCM. We used transgenic HCM mice expressing a mutated α-myosin heavy chain. Adeno-associated virus serotype 9 (AAV9) vectors were utilized to exploit their natural myocardial tropism. Three groups of mice were treated via tail-vein injections at four weeks of age (week one of study); Group 1, No HCM control (C57bl/6, no transgenic α-myosin heavy chain, n=6); Group 2, Untreated HCM mice with transgenic α-myosin heavy chain (PBS treated, n=10); Group 3, AAV9-BNP vector-treated HCM mice (n=6). To observe therapeutic benefit we assayed non-invasive blood pressure, myocardial architecture and remodeling (echocardiography), exercise capacity (treadmills), and any cardiorenal interplay through renal parameters. At 6, 9, 12, 15 and 25 weeks after AAV vector administration, left ventricular mass by echo was significantly higher in the untreated HCM group than the AAV-BNP-treated HCM and wildtype C57bl/6 mice. Significant increases in IVS and posterior wall thickness were also observed in control HCM group. At 11, 19, and 25 weeks after AAV vector administration, exercise capacity, monitored by treadmill tolerance, was significantly lower in the control HCM group than the AAV-BNP-treated HCM mice. No significant changes were seen in urine outputs. HCMAAV9-BNP treated mice showed a trend towards a lower blood pressure than both C57bl/6 and HCM mice. Our data demonstrate that AAV9-mediated BNP over-expression blocks progressive left ventricular enlargement and improves exercise capacity in a mouse model of HCM. The present study supports the BNP/GC-A/cGMP axis as a novel therapeutic target for the treatment of HCM.
Assessment of the Temporal Relationship Between Left Ventricular Relaxation and Filling During Early Diastole Using Pulsed Doppler Echocardiography and Tissue Doppler Imaging
Authors: Yukiko Onose, Takashi Oki, Tomotsugu Tabata, Hirotsugu Yamada, Susumu Ito
Journal: Circulation (1999)

The study investigated the temporal relationship between left ventricular (LV) relaxation and filling during early diastole. The transmitral flow (TMF) velocity by pulsed Doppler echocardiography and LV wall motion velocity by pulsed tissue Doppler imaging (TDI) were evaluated in 57 patients with various heart diseases and 33 normal controls. The patients were classified into 2 groups according to the ratio of the peak early diastolic to atrial systolic TMF velocity (E/A): (1) the high A group included 44 patients with an E/A ≤ 1, and (2) the pseudonormalization group included 13 patients with an E/A > 1. The isovolumic relaxation time (IRT) from the aortic component of the second heart sound (IIA) to the onset of the E wave of the TMF was measured. The peak early diastolic velocity of the LV posterior wall (Ew) and time from the IIA to the onset of the early diastolic wave (IIA-Ewo) were determined from the LV wall motion velocity assessed by pulsed TDI. The Ew was lower in the pseudonormalization and high A groups than in the control group. The IIA-Ewo was significantly longer in the pseudonormalization and high A groups than in the control group. The time constant of the LV pressure decay at isovolumic diastole (tau) correlated negatively with the Ew, and correlated positively with the IIA-Ewo in all groups. The IIA-Ewo was equal to or shorter than the IRT in control subjects, and was longer than the IRT in patients in the pseudonormalization group. In conclusion, the temporal relationship between LV relaxation and filling during early diastole varied according to the subjects' hemodynamic status. Analysis of TMF by pulsed Doppler echocardiography and LV wall motion velocity by pulsed TDI was useful for detailed evaluation of early diastolic LV hemodynamics. (Jpn Circ J 1999; 63: 209 - 215)
Abstract 4877: A modular software solution (under development) to expedite sequencing workflow and mitigate legacy workflow issues in regulatory environments
Authors: Lisa Kelly, Jessica Gordon
Journal: Cancer Research (2015)

Abstract One of the challenges of working in regulatory environments is the need to revalidate legacy workflows when incorporating new information or tools. Even in unregulated environments, updating and integrating workflows can require a considerable expenditure of time and labor. To mitigate these issues, Illumina is developing an analysis framework software as part of the Universal Oncology Test System for the MiSeqDx™ System, the first next generation sequencer to achieve FDA clearance. By incorporating plug-in workflow modules that seamlessly integrate with the framework - yet remain self-contained and separately versioned from other workflow modules - the software will expedite and ensure scalable operations. Installing new modules to the framework will incur no need for code changes to the legacy workflows, a key consideration for development and validation in regulated environments. The updated MiSeqDx analysis framework includes user authentication and sample sheet setup, reducing the number of disparate application interactions and bringing them together in a clean, clinical user interface accessible via any computer web browser. The Universal Oncology Test System software workflow module will allow an investigator to identify variants of interest via three methods: an eligibility list of specific coordinate nucleotide changes, configurable rules based on variant type and region, and an amplification gene list with specified amplification type. This flexible software solution can be used to produce, for example, clinical trial reports that require masking of non-investigational variants while not precluding the opportunity to informatically unfilter new information. A report definition can be applied per sample, and updated post-sequencing for a reanalyzed report. The in vitro diagnostic report, also in development, aims to support the pathologist end user by separate categorization of pathogenic variants based on companion diagnostics. The MiSeqDx analysis software platform combined with the Universal Oncology Test System workflow module can help expedite immediate clinical trial uptake and detection of variants for interpretation and future patient care. Citation Format: Lisa Kelly, Jessica Gordon. A modular software solution (under development) to expedite sequencing workflow and mitigate legacy workflow issues in regulatory environments. [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 4877. doi:10.1158/1538-7445.AM2015-4877
Tumor marker rise during second course high-dose chemotherapy in recurrent testicular cancer: Outcome analysis.
Authors: M. Pant-Purohit, M. J. Brames, R. Abonour, L. H. Einhorn
Journal: Journal of Clinical Oncology (2011)

4612 Background: Metastatic germ cell tumors that cannot be successfully treated by platinum based initial chemotherapy regimen are potentially curable with salvage chemotherapy. Relapsed or refractory testicular cancer has been treated at Indiana University with two courses of high-dose carboplatin and etoposide chemotherapy (HDCE), each course followed by peripheral stem cell rescue. Einhorn et al published the result of 184 consecutive recurrent metastatic patients treated 1996-2004 with two cycles of HDCE. 63% of these 184 patients were continuously NED with median follow-up 48 months (NEJM 357,340 2007). Several patients were noted to have rising tumor markers—hCG and/AFP—during their second course of high-dose chemotherapy. Similar phenomenon has been noted in some patients treated subsequently. We present retrospective analysis of the frequency and outcome of a rising tumor marker at start of second course of HDCE or within 1 week after initiation of second course. Methods: 391 patients have been treated with HDCE and stem cell rescue from Feb 1996 to December 2010. Each patient received two consecutive courses of 700 mg of carboplatin per square meter of body-surface-area (BSA) and 750mg of etoposide per square meter of BSA, each for 3 consecutive days, and each followed by autologous stem cell infusion. The second HDCE was administered 3-4 weeks after the first course. Weekly tumor markers were obtained. Results: 25 of 391 (6.4%) patients were noted to have rising hCG, AFP or both at initiation or within one week of second course of HDCE. 14 patients had rising hCG (median 61.9 mIU/mL; range 3.2-8,863). 11 patient developed rising AFP (median 18.3 ng/mL; range 4.2-1,018.8). Six patients had increase in both hCG and AFP. 24 of 25 patients had a subsequent decline in tumor marker with second course HDCE. 7 of 25 (28%) patients are continuously disease free at median follow-up of 69 months (range 28-124 months). Conclusions: Tumor marker rise during second course of HDCE is uncommon. Although it represents an adverse prognostic variable, cure is still possible with institution of second course of HDCE.
Intra-operative hyperspectral imaging for brain tumour detection and delineation: Current progress on the HELICoid project
Authors: S. Kabwama, D. Bulters, H. Bulstrode, H. Fabelo, S. Ortega, G.M. Callico, B. Stanciulescu, R. Kiran, D. Ravi, A. Szolna, J.F. Piñeiro
Journal: International Journal of Surgery (2016)
Off-Tumor Target Expression Levels Do Not Predict CAR-T Cell Killing: A Foundation For The Safety Of CD44v6-Targeted T Cells
Authors: Monica Casucci, Benedetta Nicolis di Robilant, Laura Falcone, Barbara Camisa, Margherita Norelli, Bernhard Gentner, Pietro Genovese, Maurilio Ponzoni, Aurore Saudemont, Claudio Bordignon, Luigi Naldini, Fabio Ciceri, Gianpietro Dotti, Chiara Bonini, Attilio Bondanza
Journal: Blood (2013)