tbuckley/cabot-search huggingface dataset:
Long Noncoding RNA <i>NEAT1</i>, Regulated by the EGFR Pathway, Contributes to Glioblastoma Progression Through the WNT/<b>β</b>-Catenin Pathway by Scaffolding EZH2
Authors: Qun Chen, Jinquan Cai, Qixue Wang, Yunfei Wang, Mingyang Liu, Jingxuan Yang, Junhu Zhou, Chunsheng Kang, Min Li, Chuanlu Jiang
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Long noncoding RNAs have been implicated in gliomagenesis, but their mechanisms of action are mainly undocumented. Through public glioma mRNA expression data sets, we found that NEAT1 was a potential oncogene. We systematically analyzed the clinical significance and mechanism of NEAT1 in glioblastoma. Experimental Design: Initially, we evaluated whether NEAT1 expression levels could be regulated by EGFR pathway activity. We subsequently evaluated the effect of NEAT1 on the WNT/β-catenin pathway and its target binding gene. The animal model supported the experimental findings. Results: We found that NEAT1 levels were regulated by EGFR pathway activity, which was mediated by STAT3 and NFκB (p65) downstream of the EGFR pathway. Moreover, we found that NEAT1 was critical for glioma cell growth and invasion by increasing β-catenin nuclear transport and downregulating ICAT, GSK3B, and Axin2. Taken together, we found that NEAT1 could bind to EZH2 and mediate the trimethylation of H3K27 in their promoters. NEAT1 depletion also inhibited GBM cell growth and invasion in the intracranial animal model. Conclusions: The EGFR/NEAT1/EZH2/β-catenin axis serves as a critical effector of tumorigenesis and progression, suggesting new therapeutic directions in glioblastoma. Clin Cancer Res; 24(3); 684–95. ©2017 AACR.
The <i>NOTCH4</i>–<i>HEY1</i> Pathway Induces Epithelial–Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma
Authors: Takahito Fukusumi, Theresa W. Guo, Akihiro Sakai, Mizuo Ando, Shuling Ren, Sunny Haft, Chao Liu, Panomwat Amornphimoltham, J. Silvio Gutkind, Joseph A. Califano
Journal: Clinical Cancer Research (2017)

Purpose: Recently, several comprehensive genomic analyses demonstrated NOTCH1 and NOTCH3 mutations in head and neck squamous cell carcinoma (HNSCC) in approximately 20% of cases. Similar to other types of cancers, these studies also indicate that the NOTCH pathway is closely related to HNSCC progression. However, the role of NOTCH4 in HNSCC is less well understood.Experimental Design: We analyzed NOTCH4 pathway and downstream gene expression in the TCGA data set. To explore the functional role of NOTCH4, we performed in vitro proliferation, cisplatin viability, apoptosis, and cell-cycle assays. We also compared the relationships among NOTCH4, HEY1, and epithelial-mesenchymal transition (EMT)-related genes using the TCGA data set and in vitro assays.Results:HEY1 is specifically upregulated in HNSCC compared with normal tissues in the TCGA data set. NOTCH4 is more significantly related to HEY1 activation in HNSCC in comparison with other NOTCH receptors. NOTCH4 promotes cell proliferation, cisplatin resistance, inhibition of apoptosis, and cell-cycle dysregulation. Furthermore, NOTCH4 and HEY1 upregulation resulted in decreased E-cadherin expression and increased Vimentin, Fibronectin, TWIST1, and SOX2 expression. NOTCH4 and HEY1 expression was associated with an EMT phenotype as well as increased invasion and cell migration.Conclusions: In HNSCC, the NOTCH4-HEY1 pathway is specifically upregulated, induces proliferation and cisplatin resistance, and promotes EMT. Clin Cancer Res; 24(3); 619-33. ©2017 AACR.
Effects of <i>FCGR3A</i> and <i>FCGR2A</i> polymorphisms on outcomes of patients with diffuse large B-cell lymphoma treated with CHOP-like chemotherapy versus CHOP-rituximab
Authors: J. Vose, F. Loberiza, J. Armitage, P. Bierman, R. Bociek, D. Dornan
Journal: Journal of Clinical Oncology (2009)

8567 Background: The addition of rituximab to cyclophosphamide/ doxorubicin/ vincristine/ prednisone (R-CHOP) therapy for diffuse large B-cell lymphoma (DLBCL) has significantly improved the outcome for many patients (pts). We evaluated the impact of single nucleotide polymorphisms (SNPs) of Fc receptor (FcR) genes FCGR3A and FCGR2A on the outcomes of patients with DLBCL treated with R-CHOP compared to a historical control patientss treated with CHOP-like chemotherapy alone. Methods: 199 patients with DLBCL who had received CHOP or CHOP-like chemo (N=99) or R-CHOP (N=100) had tissue blocks assayed for FCGR3A and FCGR2A polymorphisms. The patient characteristics, progression-free survival (PFS), and overall survivals (OS) were compared and analyzed with respect to the polymorphisms. Results: In the univariate analysis, the probability of PFS of pts according to polymorphisms in the FCGR2A gene treated with CHOP-like chemotherapy; H/H (n=25), H/R (n=39), and R/R (n=35) and those treated with R-CHOP; H/H (n=24), H/R (n=41), and R/R (n=35) were both not statistically different; log-rank p=0.47 and p=0.86, respectively. The probability of PFS in the FCGR3A gene treated with CHOP-like chemotherapy; V/V (n=10), F/V (n=40), F/F (n=49) and those treated with R-CHOP; V/V (n=12), F/V (N=40), F/F (n=48) were also not statistically different; log-rank p=0.32 and p=0.22, respectively. In a multivariate analysis for risk of progression or death: FCGR2A : H/H vs. H/R or R/R by treatment type: CHOP-like [RR 0.63 (95% CI 0.37–1.08), p=0.10] and R-CHOP [RR 0.59 (0.36–0.96), p=0.04] and for FCGR3A V/V vs. F/V or F/F by treatment arm: CHOP-like [RR 0.75 (0.36–1.54), p=0.43] and R-CHOP [RR 2.28(0.70–7.44), p=0.17]. Conclusions: Generally, the addition of rituximab to CHOP chemotherapy results in better outcomes than patients who receive CHOP-like regimen regardless of polymorphisms. However, our study also suggests that a trend toward association of certain polymorphisms with clinical outcomes. Additional, larger studies are needed to confirm this data. This information may assist in targeting additional therapies in patients with less favorable outcomes. [Table: see text]
Palliation of urinary obstruction from advanced prostate cancer with SBRT.
Authors: Lauren Boreta, David Ronan Raleigh, Mack Roach
Journal: Journal of Clinical Oncology (2017)

246 Background: In patients with advanced prostate cancer (PCa), urinary obstruction (UO) can lead to urinary retention requiring indwelling or suprapubic catheterization, which negatively impacts quality of life. Palliative options for UO from advanced PCa include surgical and medical treatment. Surgical intervention, including prostatectomy, pelvic exenteration and TURP, may confer undue risk to patients with advanced disease. Medical palliation may require months to take effect. Stereotactic Body Radiotherapy (SBRT) is a non-invasive technique that delivers high-dose and highly conformal radiation in ≤5 fractions, often used to treat PCa and metastatic disease. Here, we reviewed the utility of SBRT to treat UO from advanced PCa. Methods: A retrospective review of patients undergoing SBRT for UO was completed at a single institution between 2011 and 2017. Stage, PSA at diagnosis and time of treatment were recorded. Assessment of urinary function by IPSS/SHIM and documentation of catheterization were reviewed at consultation andsubsequent follow-up. Results: A total of 3 patients were treated with SBRT to the prostate for the palliation of urinary obstruction. Patient ages were 67, 57 and 52 years, and all had high risk, stage IV disease, Gleason 4+4 or 4+5, T3 or T4, with regional nodal, bony or visceral metastases. All patients required indwelling catheterization for an average 4 months prior to SBRT. Two patients were treated with whole pelvis irradiation after SBRT. In those who received subsequent pelvic irradiation, the SBRT doses to the prostate were 19 Gy in 2 fractions. The patient treated with SBRT monotherapy received 38 Gy in 4 fractions. Catheters were successfully removed in all 3 patients, one at the completion of radiation, and the others within 4 weeks of completion. With follow-up ranging from 1.2 to 6 years, no patients required re-catheterization, and there were no reports of grade ≥3 acute or long-term toxicity. Conclusions: SBRT is an effective treatment to palliate UO from locally advanced PCa, leading to removal of urinary catheters and presumed improved in quality of life. Further investigation is required to establish the optimal dose and fractionation of palliative SBRT for UO from PCa.
Tuning in to art: A predictive processing account of negative emotion in art
Authors: Sander Van de Cruys, Rebecca Chamberlain, Johan Wagemans
Journal: Behavioral and Brain Sciences (2017)

Abstract We use the example of art-derived solace to discuss a broader mechanism by which negative affect is instrumental in creating positive appreciation of artworks. Based on the theory of predictive processing, we argue that increasing attunement or reduction of prediction errors, which implies increasing validation of the agents (models), is experienced as positive, even if the artwork's content is negative.
GPs to seek legal advice over smartphone appointment service
Authors: Gareth Iacobucci
Journal: BMJ (2017)

GPs’ representatives are to seek legal advice in a bid to challenge the rollout of a service offering “virtual” GP consultations to patients by smartphone.

An emergency motion passed by England’s local medical committees has demanded that the BMA’s General Practitioners Committee seek “urgent legal advice regarding the options available and the potential for a judicial review” to challenge the introduction of the GP at Hand service, which is being piloted in west London.

The motion, passed at last week’s annual conference of LMCs, which represent GPs locally, said that it “deplores” the use of public funds to promote “inequitable access …
Patient-specific evolution of renal function in chronic heart failure patients dynamically predicts clinical outcome in the Bio-SHiFT study
Authors: Milos Brankovic, K. Martijn Akkerhuis, Nick van Boven, Sharda Anroedh, Alina Constantinescu, Kadir Caliskan, Olivier Manintveld, Jan Hein Cornel, Sara Baart, Dimitris Rizopoulos, Hans Hillege, Eric Boersma, Victor Umans, Isabella Kardys
Journal: Kidney International (2017)
The Evolving Nature of Infective Endocarditis in Spain
Authors: Carmen Olmos, Isidre Vilacosta, Cristina Fernández-Pérez, José L. Bernal, Carlos Ferrera, Daniel García-Arribas, Carlos N. Pérez-García, J. Alberto San Román, Luis Maroto, Carlos Macaya, Francisco J. Elola
Journal: Journal of the American College of Cardiology (2017)
Biomarker analysis of TPD regimen (trastuzumab, ertuzumab and docetaxel) for advanced HER2-positive breast cancer by HER family expression
Authors: K. Takada, S. Kashiwagi, W. Goto, Y. Asano, T. Takashima, T. Morisaki, S. Noda, N. Onoda, K. Hirakawa, M. Ohira
Journal: Annals of Oncology (2017)
Change in Testing, Awareness of Hemoglobin A<sub>1c</sub> Result, and Glycemic Control in US Adults, 2007-2014
Authors: Saeid Shahraz, Anastassios G. Pittas, Mojdeh Saadati, Cindy P. Thomas, Christine M. Lundquist, David M. Kent
Journal: JAMA (2017)

In 2014, an estimated 30.3 million people (9.4%) in the United States had diabetes. 1Improving glycemic control reduces the risk of diabetes-related vascular complications. 2 Studies have shown improvement in glycemic control in the United States from 1998 through 2010, as measured by hemoglobin A 1c (HbA 1c ). 3,4We examined recent trends in glycemic control and patient awareness of HbA 1c test results and targets.
Emergence of High-Avidity Melan-A–Specific Clonotypes as a Reflection of Anti–PD-1 Clinical Efficacy
Authors: Sylvain Simon, Virginie Vignard, Emilie Varey, Tiphaine Parrot, Anne-Chantal Knol, Amir Khammari, Nadine Gervois, Francois Lang, Brigitte Dreno, Nathalie Labarriere
Journal: Cancer Research (2017)

Abstract Therapeutic strategies using anti–PD-1–blocking antibodies reported unparalleled effectiveness for melanoma immunotherapy, but deciphering immune responses modulated by anti–PD-1 treatment remains a crucial issue. Here, we analyzed the composition and functions of the large Melan-A–specific T-cell repertoire in the peripheral blood of 9 melanoma patients before and after 2 months of treatment with anti–PD-1. We observed amplification of Melan-A–specific Vß subfamilies undetectable before therapy (thereafter called emerging Vß subfamilies) in responding patients, with a predominant expansion in patients with a complete response. These emerging Vß subfamilies displayed a higher functional avidity for their cognate antigen than Vß subfamilies not amplified upon anti–PD-1 therapy and could be identified by a sustained coexpression of PD-1 and TIGIT receptors. Thus, in addition to the emergence of neoantigen-specific T cells previously documented upon anti–PD-1 therapy, our work describes the emergence of high-avidity Melan-A–specific clonotypes as a surrogate marker of treatment efficacy. Cancer Res; 77(24); 7083–93. ©2017 AACR.
Abstract 21359: Safety of Repeat Radiofrequency Ablation in Atrial Fibrillation Patients With Moderate Pulmonary Vein Stenosis
Authors: Mohammad-Ali Jazayeri, Venkat Vuddanda, Jaya Pitchika, Mounika Gangireddy, Saisree Reddy Adla Jala, Madhav Lavu, Valay Parikh, Mohit K Turagam, Sudharani Bommana, Donita Atkins, Rhaguveer Dendi, Martin P Emert, Rhea C Pimentel, Seth H Sheldon, Loren Berenbom, Dhanunjaya R Lakkireddy, Madhu Reddy
Journal: Circulation (2017)

Introduction: Radiofrequency catheter ablation (RFCA), an effective treatment for atrial fibrillation (AF), is rarely complicated by severe pulmonary vein stenosis (PVS) requiring intervention. We sought to evaluate the safety of repeat RFCA in AF patients with moderate PVS after index RFCA. Hypothesis: We hypothesized, in patients with moderate PVS, repeat RFCA would not result in significant progression of PVS. Methods: We performed a retrospective, observational study of all patients who developed moderate PVS (decrease in the PV cross sectional area ≥50% but &lt;75%) after index RFCA for AF. RFCA was performed with standard techniques for pulmonary vein antral isolation. All patients underwent CT scan of the heart with contrast prior to their first ablation and 3 months after each ablation procedure. Additional CT scans were completed per provider discretion in follow-up. Results: Of a total of 2550 AF patients who underwent RFCA from 2011-2016, 165 (6.4%) developed moderate PVS of at least one PV. Mean age was 65 ± 11 years, with 130 (79%) males and 113 (68%) with paroxysmal AF. Right superior, right inferior, left superior and left inferior PVs were involved in 31%, 29%, 41%, and 20% of patients, respectively. Of these 165 patients, 78 (47%) underwent repeat CT scan (with or without redo ablation), and 48 (29%) underwent redo RFCA in the antrum of the involved PV. Mean times between CT1-CT2 and CT2-CT3 were 6 and 11 months, respectively. On repeat CT, 6 (8%) developed severe PVS of at least one PV. There was no statistical difference in the incidence of severe PV stenosis between those who underwent repeat ablation compared to those who did not (4.2 vs. 14.3 respectively; p = 0.185) Conclusions: Repeat RFCA for AF in patients with prior moderate PV stenosis appears to be safe with an acceptable risk (4.2%) of developing severe PV stenosis.
Inclusion of spiritual pain in patient reported outcome assessments as part of an integrative medicine physician consultation.
Authors: Gabriel Lopez, Wenli Liu, Minxing Chen, Yisheng Li, Alejandro Chaoul, Eduardo Bruera, Lorenzo Cohen, Marvin Delgado-Guay
Journal: Journal of Clinical Oncology (2017)

190 Background: Complementary and integrative health services are increasingly available to patients at cancer centers to help address physical and psychological needs. We review inclusion of spiritual pain (SP) as part of patient reported outcome (PRO) assessments in patients presenting for an outpatient integrative medicine consultation at a comprehensive cancer center. Methods: PRO data were collected as part of outpatient physician consultations at an integrative medicine clinic; we reviewed data between January 2013 and April 2017. Patients completed the Edmonton Symptom Assessment Scale (ESAS-FS, 12 symptoms, scale 0-10, 10 worst possible) immediately prior to the clinical encounter. ESAS distress subscales analyzed included psychological, physical, and global. Statistical analyses included summary statistics, two sample t-tests, correlations, and logistic regression. Results: We analyzed data from 4348 unique participants. Demographics included 65% women, average age 55.5, 78% Caucasian, 72% married or with significant other, majority Christian non-Catholic (49%) followed by non-specified (23%), and Catholic (20%). Overall, 41% of patients reported SP at baseline. Patients reporting a SP score of ≥ 1 (n = 1549) reported significantly higher levels of global, physical, and psychological distress than patients with SP scores of 0 (n = 2275) (all p’s &lt; 0.001). Older patients and men were less likely to report SP. SP clustered with psychological symptoms of depression and anxiety (reliability coefficient 0.76). Conclusions: A significant number of cancer patients presenting for integrative medicine consultations reported having SP, with SP clustering with psychological versus physical symptoms. More research is needed to better understand how routine screening for SP contributes to assessments of overall psychological health.
Association of non-alcoholic steatohepatitis with subclinical myocardial dysfunction in non-cirrhotic patients
Authors: Yong-ho Lee, Kwang Joon Kim, Myung eun Yoo, Gyuri Kim, Hye-jin Yoon, Kwanhyeong Jo, Jong-Chan Youn, Mijin Yun, Jun Yong Park, Chi Young Shim, Byung-Wan Lee, Seok-Min Kang, Jong-Won Ha, Bong-Soo Cha, Eun Seok Kang
Journal: Journal of Hepatology (2017)
Prediction model of low risk recurrence distinguished by 21-gene recurrence score in hormone receptor-positive invasive breast cancer: A validation study
Authors: Y. Tsuchida, N. Hayashi, F. Omata, S. Ohde, Y. Kanada, S. Tazawa, M. Takimoto, K. Suzuki, S. Nakamura, H. Yamauchi
Journal: Annals of Oncology (2017)
Modeling the Subclonal Evolution of Cancer Cell Populations
Authors: Diego Chowell, James Napier, Rohan Gupta, Karen S. Anderson, Carlo C. Maley, Melissa A. Wilson Sayres
Journal: Cancer Research (2017)

Abstract Increasing evidence shows that tumor clonal architectures are often the consequence of a complex branching process, yet little is known about the expected dynamics and extent to which these divergent subclonal expansions occur. Here, we develop and implement more than 88,000 instances of a stochastic evolutionary model simulating genetic drift and neoplastic progression. Under different combinations of population genetic parameter values, including those estimated for colorectal cancer and glioblastoma multiforme, the distribution of sizes of subclones carrying driver mutations had a heavy right tail at the time of tumor detection, with only 1 to 4 dominant clones present at ≥10% frequency. In contrast, the vast majority of subclones were present at &amp;lt;10% frequency, many of which had higher fitness than currently dominant clones. The number of dominant clones (≥10% frequency) in a tumor correlated strongly with the number of subclones (&amp;lt;10% of the tumor). Overall, these subclones were frequently below current standard detection thresholds, frequently harbored treatment-resistant mutations, and were more common in slow-growing tumors. Significance: The model presented in this paper addresses tumor heterogeneity by framing expectations for the number of resistant subclones in a tumor, with implications for future studies of the evolution of therapeutic resistance. Cancer Res; 78(3); 830–9. ©2017 AACR.
Endoscopic full-thickness resection of gastric stromal tumor: one and done
Authors: Ming-ming Xu, Alejandro Angeles, Michel Kahaleh
Journal: Endoscopy (2017)

An 82-year-old woman with multiple comorbidities underwent upper endoscopy, which showed a 25 mm subepithelial lesion in the gastric fundus. Gastric biopsies of the antrum and body were unremarkable.
Antibiotic Prescribing for Nonbacterial Acute Upper Respiratory Infections in Elderly Persons
Authors: Mical Paul
Journal: Annals of Internal Medicine (2017)

Letters21 November 2017Antibiotic Prescribing for Nonbacterial Acute Upper Respiratory Infections in Elderly PersonsMical Paul, MDMical Paul, MDRambam Health Care Campus, Haifa, Israel (M.P.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0437 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Acute nasopharyngitis, acute sinusitis, acute laryngitis/tracheitis, and acute bronchitis can be caused by viruses, but they can also be caused by bacteria. Silverman and colleagues' (1) attempts to exclude bacterial infections are inappropriate. These infections are not microbiologically confirmed (except perhaps for pharyngitis, but whether the authors considered rapid testing for group A Streptococcus is unclear). One Cochrane review shows benefit for antibiotic treatment of sinusitis, and another shows modest benefit for antibiotics for acute bronchitis (2, 3). Silverman and colleagues did not attempt to exclude streptococcal pharyngitis. Acute nasopharyngitis is not the common cold.I am ...References1. Silverman M, Povitz M, Sontrop JM, Li L, Richard L, Cejic S, et al. Antibiotic prescribing for nonbacterial acute upper respiratory infections in elderly persons. Ann Intern Med. 2017;166:765-74. [PMID: 28492914]. doi:10.7326/M16-1131 LinkGoogle Scholar2. Lemiengre MB, van Driel ML, Merenstein D, Young J, De Sutter AI. Antibiotics for clinically diagnosed acute rhinosinusitis in adults. Cochrane Database Syst Rev. 2012;10:CD006089. [PMID: 23076918] doi:10.1002/14651858.CD006089.pub4 CrossrefMedlineGoogle Scholar3. Smith SM, Fahey T, Smucny J, Becker LA. Antibiotics for acute bronchitis. Cochrane Database Syst Rev. 2017;6:CD000245. [PMID: 28626858] doi:10.1002/14651858.CD000245.pub4 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Rambam Health Care Campus, Haifa, Israel (M.P.)Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L17-0437. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAntibiotic Prescribing for Nonbacterial Acute Upper Respiratory Infections in Elderly Persons Michael Silverman , Marcus Povitz , Jessica M. Sontrop , Lihua Li , Lucie Richard , Sonny Cejic , and Salimah Z. Shariff Antibiotic Prescribing for Nonbacterial Acute Upper Respiratory Infections in Elderly Persons Michael Silverman , Marcus Povitz , Jessica M. Sontrop , and Salimah Z. Shariff Metrics 21 November 2017Volume 167, Issue 10Page: 757-758KeywordsAntibioticsBronchitisCommon coldDisclosureElderlyPharyngitisStreptococcal infectionsStreptococcal pharyngitisStreptococcusUpper respiratory tract infections ePublished: 21 November 2017 Issue Published: 21 November 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...