tbuckley/cabot-search huggingface dataset:
Metabolism‐induced tumor activator 1 (MITA1), an Energy Stress–Inducible Long Noncoding RNA, Promotes Hepatocellular Carcinoma Metastasis
Authors: Meilin Ma, Haixia Xu, Geng Liu, Jing Wu, Chunhua Li, Xiuxuan Wang, Sifan Zhang, Heng Xu, Shenggen Ju, Wei Cheng, Lunzhi Dai, Yuquan Wei, Yan Tian, Xianghui Fu
Journal: Hepatology (2019)

Metastasis is the main cause of cancer‐related death, yet the underlying mechanisms are still poorly understood. Long noncoding RNAs (lncRNAs) are emerging as crucial regulators of malignancies; however, their functions in tumor metastasis remain largely unexplored. In this study, we identify a lncRNA, termed metabolism‐induced tumor activator 1 ( MITA1 ), which is up‐regulated in hepatocellular carcinoma (HCC) and contributes to metastasis. MITA1 , a chromatin‐enriched lncRNA discovered by our nuclear RNA sequencing, is significantly induced by energy stress. This induction of MITA1 is governed by the liver kinase B1–adenosine monophosphate‐activated protein kinase (LKB1‐AMPK) pathway and DNA methylation. Knockdown of MITA1 dramatically inhibits the migration and invasion of liver cancer cells in vitro and HCC metastasis in vivo . Mechanistically, MITA1 promotes the epithelial–mesenchymal transition, an early and central step of metastasis, which may partly attribute to an increase in Slug (snail family zinc finger 2) transcription. MITA1 deficiency reduces the expression of the mesenchymal cell markers, especially Slug, whereas Slug overexpression greatly impairs the effects of MITA1 deficiency on HCC migration and invasion. Correspondingly, there is a positive correlation between the levels of MITA1 and Slug precursors in HCC tissues. Conclusion : Our data reveal MITA1 as a crucial driver of HCC metastasis, and highlight the identified AMPK‐MITA1‐Slug axis as a potential therapeutic strategy for HCC.
Preclinical Alzheimer Disease and the Dawn of the Pre-Caregiver
Authors: Emily A. Largent, Jason Karlawish
Journal: JAMA Neurology (2019)

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 Neurology 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 Neurology journal
Abstract P289: Effects of Dietary App-Supported Tele-Counseling on Sodium Intake, Diet Quality, and Blood Pressure in Patients With Diabetes and Kidney Disease
Authors: Alex R Chang, Lisa Bailey-Davis, Christina Yule, Sara Kwiecen, Elisabeth Graboski, Stephen Juraschek, Caitlin Krekel, Charlotte Collins, Cheryl Anderson
Journal: Circulation (2019)

Background: Despite the importance of healthy diet for cardiovascular (CVD) health, the vast majority of patients with chronic kidney disease (CKD) do not receive dietitian counseling or make dietary modifications. Evidence for using dietary apps and tele-counseling to improve CVD risk factors is limited. Methods: We examined the effects of dietary app-supported tele-counseling on sodium intake and diet quality in 44 patients with type 2 diabetes and stage 1-3a CKD. Patients recorded and shared dietary data via MyFitnessPal with registered dietitians, who used motivational interviewing to provide telephone counseling weekly for 8 weeks. Outcomes included 24-hour urine sodium (2 collections per timepoint), Healthy Eating Index (HEI) 2015 score (multiple 24-hour dietary recalls per timepoint), 24-hour systolic blood pressure (SBP), and 24-hour urine albumin excretion. We report interim results for patients who completed 8-week and 6-month data collection; final outcome data at 12 months will be completed in November 2018. Results: Out of 44 consented patients (mean age 60.3 ± 11.9 y, 43% female, 93% white, 20% &lt;$25,000 annual income, 84% hypertension), 32 (73%) completed 8-week follow-up and 29 (66%) completed 6-month follow-up. While 78% owned a smartphone, 52% entered dietary data using a computer. Among patients who completed 6-month follow-up, sodium excretion did not significantly decrease from baseline to 8 weeks (-345 mg/d, 95% CI: -865, 175) or 6 months: (-182 mg/d, CI: -460, 97) (Table) . However, HEI-2015 score improved by 3.19 (CI: 0.51-5.87) at 8 weeks and 7.21 (CI: 3.07, 11.3) at 6 months; 24-hour SBP improved by -3.7 (CI: -7.4, 0.1) at 8 weeks and by -4.9 (CI: -8.8, -0.9) at 6 months. Conclusions: An app-supported tele-counseling program with a registered dietitian appears to be a feasible strategy to improve dietary quality and blood pressure, even in patients with diabetes and early CKD. Sodium is ubiquitous in the food supply and hard to change at the individual level. Studies to demonstrate efficacy are needed.
Implications of high expression of miR17-92 cluster in ovarian cancer (OvCa) tissue found in long term survivors.
Authors: Devika Prasanna, Ahmad Bassam Shaker, Alejandro Recio Boiles, Michaela Oswald, Cathleen Mason, Mary Keogh, Annette Lee, Iuliana Shapira
Journal: Journal of Clinical Oncology (2015)

e12561 Background: Specific tissue miRNAs play an important role in tissue identity, differentiation and function. MiR-17-92 cluster is deleted in 20% of ovarian cancers. This is essential in embryonal and immune system development. Long term survival in OvCa may correlate with miR expression. We set out to identify levels of miR17-92 in OvCa tissue that correlated with the patients’ long-term outcomes. Methods: Tissue miRNAs were collected at surgery - tumor and benign (control) ovary from consented women. Taqman OpenArray panel was used to simultaneously run 745 microRNA using Biosystems Openarray RtPCR; 2-tailed t-test was used for all 2-sample comparison and ANOVA followed by Benjamin-Hochberg method for multiple testing to limit the false discovery rate (FDR) at the 5% level. Target scan context+ scores identified mRNAs regulated by miR17-92. Reactome constructed deregulated pathways. Results: Mean age at surgery 65 (range 51-78), 11 race matched women – mean age of 58 (range 25-67); 21 patients died < 36 mo of OvCa (SOS) & 21 patients survived > 5 years (LOS). OvCa from p alive > 5 yrs had > 10 fold miR-17 and 19b compared to those who died within 36 months post surgery p < 0.005. MiR-17-92 deregulated 29-38% MAP3K2; TBC1D20; PKD2; ELK4; ZNFX1; ANKRD52; AAK1; RORA; NCOA3; ATG7; DLGAP2; ZFP91; FAM102A mRNAs. Pathways: Adaptive immune system antigen processing and presentation FDR 8.4E-1, regulation of PPARa, ketone metabolism FDR 5.1E-1; circadian clock RORA FDR1.2E-1 were affected. Conclusions: miR-17-92 repressed antigen presentation(folding, assembly and peptide loading of MHC class 1) and Ub-proteolysis of peptides trimmed by ER destined for transportation to cell membranes. These miRs also appear to downregulate corepressors NCoR and HDAC3 allowing for gene transcription. OvCa patient surviving > 5 years have higher tissue expression of miR-17-92 repressing genes of circadian clock, adaptive immune system and upregulating transcription factors involved in opening chromatin.
Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): Clinical Features, Treatment, and Outcome. a Single Institution Result of 145 Patients from the Middle East
Authors: Saad Akhtar, Amani Al-Kofide, Nasir Bakshi, Mohammed Shamayel, Yasser Khafaga, Suleimman Al-Sweedan, Tusneem Elhassan, M S Rauf, Irfan Maghfoor
Journal: Blood (2017)
Modeling of prognostication and differential genomic expression in the tumor microenvironment of clear cell renal cell carcinoma.
Authors: Sunyoung S. Lee, Seok Joon Kwon, Dong Eun Lee, Seongwon Lee, Andrew Baird, Shinyoung Park, Jillian Dolan, Saby George
Journal: Journal of Clinical Oncology (2019)

557 Background: Stroma in the tumor microenvironment (TME) influences prognosis and response to therapy. Few mathematical models exist to prognosticate patients (pts), based on mRNA expressivity in the TME. Methods: Clinical outcomes data and mRNA-seq of 533 pts with clear cell renal cancer were obtained from TCGA. Expressivity of 191 genes enriched in cellular and structural elements of TME and clinical data were analyzed via machine learning, multivariate nonlinear regression with confined optimization, and Kaplan-Meier (KM) analysis. Results: Prognostication was modeled with higher risk score (RS) representing worse prognosis in each stage (Table). P/G is the ratio of genes associated with poor (61 genes) to good (14) prognosis (refer to presentation). Based on RS, pts in each stage were clustered into 2 groups (high and low RS), showing 2 KM curves with p &lt; 0.001 in each stage. Analysis of immune profiles in these 2 groups shows that in stage 1, expression of genes related to immune activation (IA) is not statistically different in high and low RS groups, but expression of genes related to immune inhibition (II) is higher in high RS group. In high RS groups of stage 2-4, IA genes are highly co-expressed with II genes. In high RS groups of all stages, expression of both IA and II genes increases as stage increases. In low RS groups, IA genes increase as stage increases, but II genes do not. Conclusions: Machine learning and mathematical modeling of RS and gene analysis show that IA genes are suppressed by high degree of II in high RS groups of advanced stages, contributing to worse prognosis. RS enables prognostication of pts encountered in the clinic, given genomic profiles. [Table: see text]
Novel mechanisms of glucocorticoid resistance in childhood acute lymphoblastic leukemia.
Authors: Richard B. Lock, Petra Bachmann, Rosemary Gorman
Journal: Cancer Research (2004)

2458  Despite dramatic improvements in treatment over the past 40 years, acute lymphoblastic leukemia (ALL) remains one of the most common causes of death from disease in childhood. Glucocorticoids are among the most effective agents used in the treatment of lymphoid malignancies, and patient response to treatment is an important determinant of long-term outcome in childhood ALL. In spite of its clinical significance, the molecular basis of glucocorticoid resistance is still poorly understood. The aim of this study was to develop an experimental model system to define clinically relevant mechanisms of glucocorticoid resistance in childhood ALL. An in vivo model of childhood ALL has been developed in our laboratory, using patient biopsies established as xenografts in immune-deficient nonobese diabetic severe-combined immunodeficient (NOD/SCID) mice. This model is highly representative of the human disease (Lock et al., Blood, 99: 4100-4108, 2002). The in vivo responses of these xenografts to the glucocorticoid dexamethasone (DEX) correlated significantly with patient outcome (p 1 μM) in xenografts from six patients, five of whom died of their disease. In contrast, four DEX-sensitive xenografts (IC50 values   2-fold in sensitive xenografts within 8 hours of treatment. In contrast, Bim induction was dramatically attenuated in DEX-resistant xenografts. These results have identified a clinically significant and novel mechanism of glucocorticoid resistance in childhood ALL, which occurs downstream of receptor-ligand interactions, but upstream of the signalling pathway resulting in Bim induction and apoptosis.
Sleep oscillation-specific associations with Alzheimer’s disease CSF biomarkers: novel roles for sleep spindles and tau
Authors: Korey Kam, Ankit Parekh, Ram A. Sharma, Andreia Andrade, Monica Lewin, Bresne Castillo, Omonigho M. Bubu, Nicholas J. Chua, Margo D. Miller, Anna E. Mullins, Lidia Glodzik, Lisa Mosconi, Nadia Gosselin, Kulkarni Prathamesh, Zhe Chen, Kaj Blennow, Henrik Zetterberg, Nisha Bagchi, Bianca Cavedoni, David M. Rapoport, Indu Ayappa, Mony J. de Leon, Eva Petkova, Andrew W. Varga, Ricardo S. Osorio
Journal: Molecular Neurodegeneration (2019)

Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ42, P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals. One-night in-lab nocturnal polysomnography (NPSG) and morning to early afternoon CSF collection were performed to measure CSF Aβ42, P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time. Spindle density during NREM stage 2 (N2) sleep was negatively correlated with CSF Aβ42, P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD. Reduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline.
Prognostic impact of C-reactive protein in primary, advanced and recurrence HNSCC.
Authors: Georgy M. Manikhas, Svetlana I. Kutukova, Andrey I. Yaremenko, Natalia P. Belyak, Svetlana S. Bozhor
Journal: Journal of Clinical Oncology (2015)

e17060 Background: The purpose of our study was to investigate the significant impact of C-reactive protein (CRP) level as a prognostic factor of relapse of HNSCC and as a predictive marker of chemotherapy efficacy . Methods: In the prospective study were investigated 35 patient with HNSCC: 18 patients with primary diagnosis I-III stage (group1) and 17 with advanced/recurrence disease (group2). All patients in group1 were treated by complex protocol (induction chemotherapy (DCF, PF), surgical resection, and postoperative RT). 17 patients of group2 were treated by chemotherapy (DCF, PF, TC or methotrexate), 3 - 8 cycles. Serum level of CRP was studied on baseline visit, after each stage of complex treatment in group1 and 1-day before of each cycle of chemotherapy in group2. Results: The average baseline CRP level in group1 was 2.19+1.22 mg/l and only 3 patients had CRP exceed ULN (6.89 mg/l), 15 patients had CRP level near LLN (0.38 - 0.74 mg/l). In group2 the average baseline CRP level was 24.69+11.98 mg/l: only 2 patients had normal range of CRP (1.33 and 2.5 mg/l), levels of 15 ones varied from 7.52 to 84.56 mg/l. Analysis of CRP level in group1 showed: 15 patient during all stage of treatment had normal CRP level (0.55 - 0.64 mg/l) and it has strong trend to decrease (clinically we registered SD or PR of tumor lesions). Only in 2 cases were registered increasing of CRP level during chemotherapy stage. In group2 3 patients had decreasing CRP level during chemotherapy (average decline from 10.0 to 40.0 mg/l with PR of target and non-target lesions). 4 patients had SD and unmodified CRP level in the treatment period. 5 patients had PD of tumor lesions and significant increasing of CRP (average increase from 17.66 to max 206.81 mg/l). Finally 9 patients had only increased level of CRP by 15-20 mg/l and this increasing was early sign of progression which was detected after 3-8 weeks (after increasing CRP). Conclusions: Our treatment demonstrate that baseline CRP level can be used as a prognostic factor in the course and relapse of HNSCC. And we detected correlation between CRP level and PD of tumor lesions during chemotherapy treatment in advanced and relapse patient’s group and it is possible to use as a predictive marker for evaluation of clinical efficacy chemothewrapy.
Abstract P055: Evaluating the Impact of the New Pediatric Clinical Practice Guideline on the Prevalence of Pediatric Hypertension and Associations With Adult Hypertension: The International Childhood Cardiovascular Cohort (i3C) Consortium
Authors: Michael Khoury, Phil Khoury, Tian Hu, Rachel Widome, Lydia Bazzano Bazzano, Trudy L Burns, Stephen R Daniels, Terry Dwyer, Johanna Ikonen, Markus Juonala, Mika Kähönen, Ronald J Prineas, Olli Raitakari, Alan Sinaiko, Julia Steinberger, Alison Venn, Jorma Viikari, Jessica G Woo, David R Jacobs, Elaine M Urbina
Journal: Circulation (2019)

Background: New pediatric hypertension (HTN) definitions were recently introduced in a clinical practice guideline (CPG). We evaluated the impact of the CPG (compared to the previous guideline, the “Fourth Report”) on the prevalence of pediatric HTN and associations with HTN in adulthood. Methods: Data from the International Childhood Cardiovascular Cohort (i3C), a consortium comprising seven large, long-standing study cohorts from the United States, Finland, and Australia, were used. The mean of 2-6 BP measurements using an auscultatory technique were obtained. BP was categorized as normal, elevated, and hypertensive (stage 1 and 2) using the Fourth Report and CPG. For those with multiple BP assessments within an age category, a random assessment was selected for analysis. Childhood participants were contacted in adulthood and data on self-reported HTN was recorded. Results: There were 34,014 youth (mean age 10.4 ± 3.1 years, 49.4% male) with 92,751 BP assessments available for analysis. Use of the CPG increased hypertension prevalence from 7.6% to 13.5% (stage 1) and 1.3% to 2.5% (stage 2, p &lt;0.0001). Among those 6 to &lt;9 years, 805/880 (91.5%) re-classified from elevated BP to stage 1 HTN (Table). The greatest reclassification from stage 1 to 2 HTN occurred among those aged 15 to &lt;18 years (294/597, 31.3%). The greatest reclassification to a lower BP category occurred among youth measured at age 13 to &lt;15 years. Of 9,591 adults (mean age 48.8 +/- 7.9 years, range 21.0 - 64.6 years), 2,913 (30.4%) had self-reported HTN. The sensitivity for predicting adult HTN among those with HTN at any point in childhood was 13.4% and 22.4% (specificity 92.3% and 85.9%), as defined by the Fourth Report and CPG, respectively. Conclusion: The CPG resulted in a significantly increased prevalence of HTN in children and adolescents due to significant re-classification to higher BP categories. While the observed increases were not consistent across age groups, the results suggest increased sensitivity regarding the development of HTN in adulthood.
Are immune checkpoint inhibitors (ICI) a valid option for papillary renal cell carcinoma (pRCC)? A multicenter retrospective study.
Authors: Manon De Vries-Brilland, Marine Gross-Goupil, Elouen Boughalem, Benoit Beuselinck, Constance Thibault, Christine Chevreau, Sylvain Ladoire, Philippe Barthelemy, Sylvie Negrier, Delphine Borchiellini, Olivier Huillard, Lionnel Geoffrois, Gwenaelle Gravis, Carolina Saldana, Antoine Thiery-Vuillemin, Valérie Seegers, Bernard Escudier, Alain Ravaud, Laurence Albiges
Journal: Journal of Clinical Oncology (2019)

582 Background: pRCC is the most common non-clear cell RCC (nccRCC) and represents up to 15% of RCC. Pivotal studies evaluating ICI mostly excluded nccRCC. Therefore the efficacy of ICI in pRCC remains to be demonstrated. Methods: We retrospectively investigated the activity and safety of PD-1/PD-L1 inhibitors (PD-1i) specifically in patients (pts) with metastatic pRCC from 15 centers in France and Belgium. Pts baseline characteristics, treatment outcome and safety were collected. Primary endpoint was time-to-treatment failure (TTF). Secondary endpoints included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs). Results: From 02/2016 to 09/2018, 50 pRCC pts treated with PD-1i were included. Median age was 63 years (range: 27-84), 36 (72%) were male. Histology included 14 (28%) type 1 pRCC, 30 (60%) type 2 pRCC, 6 (12%) unclassified pRCC. PD-1i was used in first line setting in 5 pts (10%), in second line in 29 pts (58%) and in third line or beyond in 16 pts (32%). IMDC risk group at PD-1i start was 22% good, 44% intermediate and 33% poor. ICI used were PD-1 inhibitors in 47 pts (94%) and PD-L1 inhibitors in 3 pts (6%). PD-1 in was used as monotherapy in 94% of pts. With a median follow up of 10.7 months (95% Confidence Interval (CI): 6.8-14.8), the median TTF was 3.7 months (95% CI: 3.1, 10.1). In type 1, the median TTF was 7.1 months (95% CI: 3.2-NA) and 3.2 months (95% CI: 2.9-NA) in type 2. Median treatment duration was 3.2 months (range: 0.4-24.5, IQR: 2.4-6.4). Among the 45 pts evaluable for ORR, best response was complete response/partial response in 8 pts (16%), stable disease in 13 pts (26%) and progressive disease in 24 pts (48%). ORR was 25% in type 1 pRCC and 15% in type 2 pRCC. Median OS was 17.6 months (95% CI 11.4- not reached). TRAEs of grade 3-4 were noted in 6 patients (12%) which led to treatment discontinuation, no grade 5 were observed. Conclusions: This retrospective study is the largest cohort of metastatic pRCC treated with PD-1i to date. PD-1i exhibit limited activity in this pRCC population, with better TTF and ORR in type 1 pRCC. Our findings underline the need for further prospective clinical trials evaluating ICI combinations in pts with pRCC.