tbuckley/cabot-search huggingface dataset:
Клинико-гемодинамические аспекты печеночной и внепеченочной портальной гипертензии
Authors: Yu.M. Stepanov, M.V. Chaliy
Journal: GASTROENTEROLOGY (2018)

Актуальность. Значительная вариабельность количественных показателей портального кровотока при хроническом гепатите, циррозе печени, хронической сердечной недостаточности, болезни Бадда — Киари подтверждает необходимость дальнейшего поиска клинико-гемодинамических особенностей при различных формах портальной гипертензии (ПГ). Цель. Определение связи между допплерографическими показателями портальной системы, клиническими данными и основными маркерами цитолитического, холестатического и мезенхимально-воспалительного синдромов у больных с печеночной и внепеченочной ПГ. Материалы и методы. В исследование вошли 205 пациентов с ПГ и 35 больных без ПГ, проходивших обследование и лечение в гастроэнтерологическом отделении Николаевской областной клинической больницы. Всем больным проводили клиническое обследование, допплерографию сосудов портальной системы, биохимическое исследование крови. Результаты. У больных с печеночной ПГ были обнаружены наибольшие изменения допплерографических показателей как венозного, так и артериального кровотока одновременно со значительной выраженностью маркеров цитолиза и холестаза, а выявленные достоверные корреляционные связи свидетельствуют об их ассоциативном характере. Характерной чертой внепеченочной ПГ было отсутствие признаков печеночной недостаточности или их меньшая выраженность; не обнаружено параллелизма между биохимическими и гемодинамическими показателями при этой форме ПГ.
QOL-28. CUTANEOUS REACTIONS TO TARGETED THERAPIES IN CHILDREN WITH CNS TUMORS: A CROSS-SECTIONAL STUDY
Authors: Connie Zhong, Hannah Song, Mark Kieran, Susan Chi, Karen Wright, Jennifer Huang
Journal: Neuro-Oncology (2018)

The MAPK and mTOR pathways play important roles in cell proliferation. BRAF, MEK, and mTOR inhibitors are novel therapies that inhibit these pathways and are increasingly utilized in the pediatric population with CNS tumors. While associated cutaneous reactions are common, data in children are sparse. The objective of this cross-sectional study was to investigate the frequency and type of cutaneous reactions in children with brain tumors treated with BRAF, MEK, and mTOR inhibitor monotherapy. Patients less than 21 years of age with CNS tumors on BRAF V600E (dabrafenib), MEK (trametinib), or mTOR inhibitors (everolimus) were enrolled over a one-year period. Twenty-two patients were enrolled, including 11 on MEK inhibitors, 6 on BRAF V600E inhibitors, and 5 on mTOR inhibitors. Median age at study visit was 12 years (3-19 yrs). Ninety-six percent (21/22) of patients had at least one skin finding. In patients on the MEK inhibitors (11), common reactions were follicular eruptions (9), xerosis (8), paronychia (4), and alopecia (2). In patients on the BRAF inhibitors (6), common reactions included follicular eruptions (6), hand-foot syndrome (5), and xerosis (3). In patients on the mTOR inhibitors (5), reactions included xerosis (4), paronychia (1), and follicular eruption (1). Two patients on the MEK inhibitors and one patient on the BRAF inhibitor required therapy cessation due to severe cutaneous reactions. Treatment was recommended for study participants as indicated. The study demonstrates that cutaneous reactions were extremely common but generally well-tolerated, though for a small subset, their reactions were severe and required therapy cessation.
DIPG-46. IDENTIFICATION OF CIRCULATING miRNAs IN DIPG PATIENTS AS PREDICTORS OF RESPONSE TO TARGETED THERAPY AND AS CLASSIFIERS OF CLINICAL OUTCOME
Authors: Loris De Cecco, Federica Maria Ianno’, Silvana Canevari, Elisabetta Schiavello, Andrea Anichini, Veronica Biassoni, Lorenza Gandola, Maura Massimino
Journal: Neuro-Oncology (2018)

Twenty-five consecutive children (median age 7.4 years) were enrolled according to the standard MRI inclusion criteria in a treatment strategy, initially begun on a compassionate basis, including standard dose radiotherapy, and re-irradiation at relapse with 19.8 Gy, and concomitant and adjuvant nimotuzumab and vinorelbine. One-year OS was 30 ± 10 %; median PFS and OS were 8.5 and 15 months, respectively. Serum specimens were collected at baseline, at each therapy administration and during follow-up. We used a high-throughput microRNA screening approach to assess miRNA profile in serum samples obtained from 24 of those patients with the main aim to identify novel non-invasive biomarkers able to improve the prediction of disease outcome and therapeutic sensitivity. Here we present the results of serum miRNA profiling at baseline. microRNA expression profiling was performed using Agilent platform and Human miRNA SureSelect 8x60K containing 2006 miRNAs annotated on miRBase19.0. Primary data analysis yielded a matrix containing 330 detectable miRNA. Association with PFS allowed us to disclose a signature of 10 miRNAs able to stratify high and low risk patients (HR=4.33, 95%CI 1.49–12.54; p=4.27E-05). Our signature was evaluated in longitudinal series and associated to clinical data in order to improve prediction of disease progression. At present, this is the first study that aims at investigating circulating miRNA levels in DIPG pediatric patients.
RADI-20. CHANGES IN STRUCTURAL BRAIN CONNECTIVITY WITHIN THE FRONTAL LOBES DURING CRANIAL RADIOTHERAPY IN CHILDREN TREATED FOR MEDULLOBLASTOMA
Authors: Wilburn Reddick, John Glass, Qing Ji, Heather Conklin, Julie Harreld, Giles Robinson, Amar Gajjar
Journal: Neuro-Oncology (2018)

This study assessed global and regional graph metrics to quantify the impact of craniospinal irradiation (CSI) on structural brain connectivity and efficiency. Fifty medulloblastoma patients (Age at exam 11.0 + 5.1 years [4.9-22.8 years]; 8 low-risk WNT [15 Gy CSI], 20 standard-risk [23.4 Gy CSI], 22 high-risk [36.0 Gy CSI]) were imaged Pre- and Post-CSI using 30 or 64 direction diffusion tensor imaging (DTI) with 2.0 mm spatial resolution. Probabilistic tractography was performed between 82 cortical and sub-cortical brain structures and fractional anisotropy along each tract was used to construct the structural connectome. BrainConnectomeToolbox was used to compare graph metrics Pre- and Post-CSI using a paired T-test (p<0.05 significant) for each cohort. Global graph metrics were not significantly different in any group. High-risk patients demonstrated significantly decreased regional network efficiency throughout the basal ganglia, frontal lobes (superior/middle, medial/lateral orbital, ventrolateral), anterior cingulate, and central cortex. Similarly, standard-risk patients demonstrated significantly decreased regional network efficiency throughout the same structures except the ventrolateral frontal cortex. Strikingly, the low-risk patients showed no significant decreases in regional network efficiency except in the central cortex. Decreased regional network efficiency throughout the basal ganglia, frontal lobes, and anterior cingulate in the high and standard-risk patients would be consistent with the development of later neurocognitive deficits specifically in working memory and executive function. The lack of significant differences post irradiation in the low-risk patients is consistent with less intensive therapy in the WNT sub-group reducing the potential of later neurocognitive deficits in this vulnerable cohort.
Hospice Benefits and Phase I Cancer Trials
Authors: Robert Avery
Journal: Annals of Internal Medicine (2004)

Letters6 January 2004Hospice Benefits and Phase I Cancer TrialsRobert Avery, MDRobert Avery, MDFrom St. Louis Oncology Associates, St. Louis, MO 63128.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-1-200401060-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The article by Byock and Miles (1) is an excellent brief review of some of the problems in hospice care. I do not agree, however, with the authors' opinion that phase I clinical trials should be made available to hospice patients. For cancer patients in hospice, there are no effective chemotherapies. Through the dying process, patients will eventually come to accept death as inevitable. This acceptance is important for a peaceful death. A fight to the bitter end can only produce anxiety. Chemotherapy provides hope that the end can be prolonged. This is counterintuitive to the idea ...Reference1. Byock I, Miles SH. Hospice benefits and phase I cancer trials. Ann Intern Med. 2003;138:335-7. [PMID: 12585832] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From St. Louis Oncology Associates, St. Louis, MO 63128. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoHospice Benefits and Phase I Cancer Trials Ira Byock and Steven H. Miles Hospice Benefits and Phase I Cancer Trials Donald L. Trump Hospice Benefits and Phase I Cancer Trials Ira Byock and Steven H. Miles Metrics Cited BySelf-Transcendence and Burnout in Hospice and Oncology NursesHospice Patients in Clinical Cancer Treatment Trials 6 January 2004Volume 140, Issue 1Page: 70KeywordsAdverse reactionsCancer chemotherapyClinical trialsDrug therapyEmotionsForecastingHand strengthPalliative carePatientsPhase 2 trials ePublished: 6 January 2004 Issue Published: 6 January 2004 CopyrightCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Abstract 44: NSF is Required for Plasma Membrane Blebbing Occurring in Necrotic Cell Death
Authors: Alyssa A Lombardi, Jonathan P Lambert, Jeffery D Molkentin, John W Elrod
Journal: Circulation Research (2017)

The loss of cells that occurs during MI and HF is largely due to necrotic cell death, yet the molecular mechanisms underlying necrosis, specifically plasma membrane rupture, are not well defined. A genome-wide, shRNA loss-of-function screen identified components of SNARE-mediated membrane fusion as potential facilitators of Ca 2+ and ROS-induced membrane rupture. Here, we targeted Nsf (N-ethylmaleimide sensitive factor) due to its requirement in SNARE recycling, redox sensitivity, and lack of gene homologs. Deletion of Nsf from 3T3 fibroblasts, using CRISPR-Cas9n ( Nsf -/- ), inhibited membrane rupture and improved cell viability following Ca 2+ overload (ionomycin) and ROS (H 2 O 2 ) induced cell death. Further, stable overexpression of NSF augmented membrane rupture and decreased cell viability following necrotic insults. Next, using high-resolution live cell microscopy we examined membrane blebs - herniations of the plasma membrane that precede rupture and necrosis. Nsf -/- and WT cells were treated with ionomycin or H 2 O 2 and imaged for 4h with automated Z-stack images taken every 5m. Ionomycin and H 2 O 2 induced prominent blebs in nearly every WT cell followed by membrane rupture. Strikingly, loss of Nsf ablated bleb formation (Fig 1). Studies are ongoing in cardiac-specific Nsf -/- mice to define if this novel mechanism contributes to myocyte death during IR injury. Deletion of Nsf in adult cardiomyocytes does not result in a baseline phenotype, increasing the translational potential of NSF targeted therapy. In summary, our results identify a new molecular component required for membrane blebbing that occurs during pathogenic cell death.
Pretargeting in nuclear imaging and radionuclide therapy: Improving efficacy of theranostics and nanomedicines
Authors: E. Johanna L. Stéen, Patricia E. Edem, Kamilla Nørregaard, Jesper T. Jørgensen, Vladimir Shalgunov, Andreas Kjaer, Matthias M. Herth
Journal: Biomaterials (2018)

Pretargeted nuclear imaging and radiotherapy have recently attracted increasing attention for diagnosis and treatment of cancer with nanomedicines. This is because it conceptually offers better imaging contrast and therapeutic efficiency while reducing the dose to radiosensitive tissues compared to conventional strategies. In conventional imaging and radiotherapy, a directly radiolabeled nano-sized vector is administered and allowed to accumulate in the tumor, typically on a timescale of several days. In contrast, pretargeting is based on a two-step approach. First, a tumor-accumulating vector carrying a tag is administered followed by injection of a fast clearing radiolabeled agent that rapidly recognizes the tag of the tumor-bound vector in vivo. Therefore, pretargeting circumvents the use of long-lived radionuclides that is a necessity for sufficient tumor accumulation and target-to-background ratios using conventional approaches. In this review, we give an overview of recent advances in pretargeted imaging strategies. We will critically reflect on the advantages and disadvantages of current state-of-the-art conventional imaging approaches and compare them to pretargeted strategies. We will discuss the pretargeted imaging concept and the involved chemistry. Finally, we will discuss the steps forward in respect to clinical translation, and how pretargeted strategies could be applied to improve state-of-the-art radiotherapeutic approaches.
Benefit of neoadjuvant chemotherapy for resectable gastric cancer
Authors: N. Chorna, A. Lukashenko, Y. Ostapenko, O. Kolesnik, A. Boiko
Journal: Annals of Oncology (2018)

Introduction: The gastric cancer (GC) is remains as one of the most common malignancies in Ukraine and other countries around the world, despite of a steady decline in the incidence. Over the last decades the major treatment strategy has been postoperative systemic therapy. The results of published trials were reviewed. In addition, neoadjuvant chemotherapy (NAC) was evaluated. The aim of this study was to assess the efficacy and safety of neoadjuvant chemotherapy in patients with resectable gastric cancer. Methods: Patients with GC (n = 98) randomly underwent NAC (ECF) followed by planned surgical resection, group A (n = 47) or surgery alone, group B (n = 51) at clinic of National Cancer Institute of Ukraine, between 2009 and 2016. Overall survival (OS), local control (LC) and biological markers were estimated. Results: Correlations between expression levels of molecular marker VEGFR-1 and gastric cancer tumor cells sensitivity to chemotherapy were found. Significant difference were found in 5-year overall survival rates (37,2% vs 23.4% for groups A and respectively). Primary tumors volumetry showed difference between the average value before and after NAC, 182±11.4 mm3 vs 112±8.7 mm3, p < 0.001. Conclusion: Performed analysis has been established as an evidence of practical importance of the modern molecular technologies application for the improvement of the treatment strategies for stomach cancer patients. The significance of sensitivity of VEGFR-1 to chemotherapy in patients with GC has been estimated. Determination of sensitivity to NAC is quite prospective in order to provide a reasonable treatment of patients with GC and reduce the overall cost of the treatment.
Diarrhoea in adult cancer patients: ESMO Clinical Practice Guidelines
Authors: P. Bossi, A. Antonuzzo, N.I. Cherny, O. Rosengarten, S. Pernot, F. Trippa, U. Schuler, A. Snegovoy, K. Jordan, C.I. Ripamonti
Journal: Annals of Oncology (2018)

Diarrhoea is defined as the frequent passage of loose stools with urgency (or more frequent passage than is normal for the individual). Objectively defined, it is the passage of more than three unformed stools in 24 hours [1]. Often the patient's definition of diarrhoea varies and needs to be clarified by medical staff, through an adequate assessment.
SWRK-06. PALLIATIVE CARE BEREAVEMENT INTERVENTION: AN EDUCATIONAL AND SUPPORT PROGRAM FOR NEURO-ONCOLOGY STAFF
Authors: Melissa Mark, Elizabeth Gilger, Aimee Thompson, Maryam Fouladi
Journal: Neuro-Oncology (2018)

As part of a large tertiary referral center for brain tumors, our center saw 161 new patients, 223 consults, and had 17 deaths in 2017. Along with other efforts including a neuro-oncology (N/O) family bereavement program, a quality improvement initiative on early palliative care (PC) referral for all cancer patients, the Palliative Care Bereavement Intervention (PCBI) was created in the Fall of 2017 to better educate and support the N/O team. As a baseline measure, we used the validated pediatric Moral Distress Scale (MDS-R), which has three parallel versions; physician (MD), nurse (RN/NP), and other healthcare professional (OHP). 19 team members completed the survey, 7 MD, 5 RN/NP, 7 OHP. Scores across groups showed low composite scores, but means varied by group, and were highest in physicians (50.4), then nurses (40.8), and lowest in OHPs (17.9). The most frequent/distressing scenarios were distinct to each group and the level of frequency/distress was variable in these, highest in RN, followed by MD, and OHP groups respectively. The intervention is a monthly 45 min session added on to our weekly patient care conference. The format is 20 minutes education, 15 minutes case discussion, 10 minutes bereavement/remembrance of any patient deaths from the prior month. Topics covered to date include, introduction to PC, prognostic disclosure, advanced directives, DNR orders, and condolences. Prior to this initiative, there was no formalized debriefing of patient deaths. Follow up MDS-R surveys will be completed in February 2018 and presented accordingly.
PCLN-04. BRAIN TUMOR PATIENT DERIVED ORTHOTOPIC XENOGRAFTS INDUCE TUMORS OF MOUSE ORIGIN
Authors: Andrew Strand, Bonnie Cole, Sarah Leary, James Olson
Journal: Neuro-Oncology (2018)

Between 2009 to 2014 we established 50 patient derived orthotopic xenograft (PDOX) lines representing a wide spectrum of pediatric brain tumors. Eight lines repeatedly failed short tandem repeat identity testing and genomic methylation analysis. Tumors in these eight lines had a common histologic appearance distinct from the source tumors and suggestive of hematopoietic cells. These tumors showed leptomeningeal and ventricular dissemination and were very aggressive. Human-specific antibodies did not stain the tumors. RNAseq analysis confirmed these tumors to be purely mouse. RNAseq and cell surface marker analysis suggested an early myeloid cell of origin. In a rare case, co-existence of PDOX and mouse tumor was observed in a single animal. RNAseq also revealed high expression of murine leukemia virus (MuLV). All NOD immunodeficient mice contain functional endogenous MuLV retrovirus in their genome. We are testing a model where infiltrating immune cells in the primary tumor or the tumor cells themselves provide paracrine stimulation of mouse myeloid cells, which serve as targets for retroviral transformation. These studies may help us to understand novel mechanisms relevant for brain tumor–immune system interactions. As more labs develop and share these invaluable models, it is critical to utilize quality control steps to verify the lineage of PDOX lines. Removal of the endogenous MuLV by breeding or CRISPR technology to create a “clean” host mouse strain should be a priority for the translational research community.
Abstract 20607: Suppression of MiR-143 By Poly I:C Attenuates Myocardial I/r Injury Involving Glycolytic Dependent Yap Activation
Authors: Yuanping Hu, Xiaohui Wang, Tuanzhu Ha, John Kalbfleisch, Race Kao, David Williams, Chuanfu Li
Journal: Circulation (2017)

Introduction: We observed that Toll like receptor 3 (TLR3) is required for the neonatal heart repair and regeneration after myocardial ischemic injury and TLR3 ligand, Poly (I:C) enhances glycolysi...
EPEN-18. TRANSCRIPTOMICS SEQUENCING REVEALS ABERRANT ALTERNATIVE SPLICING IN RECURRENT POSTERIOR FOSSA EPENDYMOMAS
Authors: Anbarasu Lourdusamy, Timothy Ritzmann, Hazel Rogers, Andrew Donson, Rebecca Chapman, Lisa Storer, Thomas Jacques, Simon Paine, Nicholas Foreman, Richard Grundy
Journal: Neuro-Oncology (2018)

Ependymoma is the second most common posterior fossa tumour in children and causes significant neurological morbidity and mortality. Although these tumours are morphologically similar, recent advances in genomics have revealed that posterior fossa ependymoma (PF-EPN) is actually comprised of three distinct biological entities. Despite these differences, PF-EPN commonly resists chemotherapy and majority of them will recur. Recurrent ependymoma is fatal in children, and yet little is known about its biology. We hypothesized that post-transcriptional changes such as alternative splicing could reveal the underlying mechanisms and uncover genes that would inform actionable targets for therapy. To this end, we mapped the alternative splicing landscape in 17 matched paired samples of primary-recurrent PF-EPNs in children using RNA-seq. We identified 582 differential alternative splicing (AS) events between primary and recurrent PF-EPN, covering five basic types of AS patterns with cassette exon skipping being the majority of the AS events affected (~ 63%). These AS events were enriched for cancer hallmarks important for sustained proliferation and invasion, and affecting key regulators of invasive phenotype such as CD44 and TNC. In addition, immune system genes were enriched among AS events that show shift in inclusion levels in recurrent PF-EPN. Strikingly, genes with AS events did not show significant expression changes between primary and recurrent PF-EPN at the whole-transcript level, suggesting, AS events are an independent and informative measure for defining recurrent ependymoma. Collectively, our data provides evidence for widespread splicing dysregulation in PF-EPN, and suggests the role of aberrant AS in the pathogenesis of ependymoma.
Potential impact of Helicobacter pylori-related metabolic syndrome on upper and lower gastrointestinal tract oncogenesis
Authors: Jannis Kountouras, Stergios A. Polyzos, Michael Doulberis, Christos Zeglinas, Fotini Artemaki, Elizabeth Vardaka, Georgia Deretzi, Evaggelia Giartza-Taxidou, Dimitri Tzivras, Efthymia Vlachaki, Evangelos Kazakos, Panagiotis Katsinelos, Christos S. Mantzoros
Journal: Metabolism (2018)
MBRS-32. METHYLATION PROFILE IN A RETROSPECTIVE SERIES OF SPANISH PEDIATRIC MEDULLOBLASTOMA
Authors: Idoia Martin-Guerrero, Olaia Aurtenetxe, Laura Zaldumbide, Itziar Astigarraga, Debbie Hicks, Ed Schwalbe, Steve Clifford, Miguel Garcia-Ariza, Aurora Navajas
Journal: Neuro-Oncology (2018)

Consensus molecular subgroups of Medulloblastoma (MB), namely WNT, SHH, Group 3 and Group 4, exhibit divergent biology and clinical outcomes. To date optimal ways of identifying MB subtypes are based on the analysis of transcriptional and epigenetic signatures. The present study aimed to examine clinical and molecular correlates of the MB consensus subgroups in a large retrospective series of Spanish MB samples. The study population included 86 MB patients (age <16 years at diagnosis) recruited from 18 Spanish hospitals since 1997 to 2015. The 45% of patients were classified as high risk and the 55% as standard risk. DNA methylation profiles were generated from 57 FFPE and 29 frozen tumoral tissues (66.3% FFPE and 33.7% frozen) using the Illumina Methylation EPIC Array. Clinical data including follow-up were collected. All patients were treated following SIOP collaborative brain tumor protocols. Preliminary results show that, according to the methylation profile, our series include patients belonging to WNT group (≈8%), SHH (≈24%), Group 3 (≈24%) and Group 4 (≈29%). The 86% of WNT tumors display classic histology, while the 68% of SHH group are desmoplastic/nodular. Group 3 and 4 mainly show classic histology (67 and 84%, respectively). Remarkably, the 56% of MYCC positive patients are included in the Group 3. The study of DNA methylation profiling in a Spanish MB series has enabled the molecular classification of MB samples, improving disease-risk stratification. This project was supported by Asociación Pablo Ugarte and Pequeropa.