tbuckley/cabot-search huggingface dataset:
Abstract 077: Small Heterodimer Partner, An Orphan Nuclear Receptor, Inhibits Cardiac Hypertrophy
Authors: Yoon Seok Nam, Hae Jin Kee Kee, Yoojung Kim, Gwang Hyeon Eom, Sera Shin, Don-Kyu Kim, Hueng-Sik Choi, Hosouk Joung, Young Kuk Cho, Jeong-Hyeon Ko, Nakwon Choe, Hyun Kook
Journal: Circulation Research (2013)

Background: Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor lacking DNA binding domain. SHP directly modulates the activities of other nuclear receptors and regulates a variety of cellular events such as cell differentiation, proliferation, and metabolism in various tissues. However, the role of SHP in heart has not yet been elucidated. Thus, in this study, we tried to investigate the functional roles of SHP in heart physiology and in the development of cardiac hypertrophy. Methods and Results: We observed that SHP knock-out mice elicited cardiac hypertrophic features determined by heart weight to body weight or to tibia length ratios. Fetal genes, such as atrial natriuretic factor (ANF) or beta myosin heavy chain (βMHC) were significantly up-regulated in SHP knockout mice heart. In neonatal rat ventricular cardiomyocytes (NRVCs), phenylephrine (PE) reduced promoter activation of SHP and decreased protein level of SHP. Adenovirus-mediated over-expression of SHP (Adeno-SHP) significantly reduced hypertrophic responses induced by PE as assayed by [3H]-leucine incorporation, Nppa promoter activity, and cell size measurement. Adeno-SHP significantly reduced hypertrophy-associated proteins. In contrast, knock-down of SHP by small hairpin RNA, decreased both Myh7 and Nppa promoter activities, whereas it up-regulated ANF or α-tubulin expressions. Metfomin (N,N-Dimethylimidodicarbonimidic diamide), an anti-diabetic agent, up-regulated SHP in dose-response fashion. PE-induced activation of Nppa promoter and [3H]-leucine incorporation were completely blocked by metformin. PE-induced down-regulation of SHP was blunted by simultaneous treatment of metformin. Metformin-mediated antihypertrophic action was not observed when the SHP was down-regulated by small interfering RNA against to SHP. Conclusions: These results suggest that atypical orphan nuclear receptor SHP prevents cardiac hypertrophy and it mediates metformin-mediated antihypertrophic responses, implicating that theses signal cascades may serve as a novel therapeutic target of treatment of hypertrophic cardiomyopathy patients.
Association of increased survival in glioblastoma patients treated with dendritic cell vaccinations and temozolomide with increased activity of NK cells and ABCC3 expression.
Authors: Gaetano Finocchiaro, Marica Eoli, Elena Anghileri, Sara Pessina, Simona Frigerio, Bianca Pollo, Valeria Cuccarini, Carlo Antozzi, Maura Servida, Maria Grazia Bruzzone, Eugenio Agostino Parati, Serena Pellegatta
Journal: Journal of Clinical Oncology (2016)

2039 Background: In the two stage phase I-II study DENDR-I, 24 patients with first diagnosis of glioblastoma (GBM) were treated with DC immunotherapy associated to standard radio-chemotherapy. To go to stage II progression-free survival (PFS) 12 months after surgery (PFS-12) was expected in at least 8 cases. Evidence of immune response was investigated. Methods: Patients with post-surgery volume ≤ 10 cc underwent leukapheresis before radiotherapy and chemotherapy with temozolomide (TMZ). Three intradermal injections of mature DC loaded with whole tumor lysate were done before and four after adjuvant TMZ. Results: The treatment was well tolerated. After a median follow up of 18.8 months 10 patients reached PFS12 (responders). Median overall survival (OS) was 19.4 mo comparing favorably with OS expected using the EORTC nomogram model 3 of 13.0 mo (p = 0.01). The immune activation of effector cells was assessed by intracellular staining of interferon-gamma (IFN-γ) in PBLs of 5 responders and 6 non-responders. In responders DC vaccination induced a significant expansion of NK cells producing IFN- γ after the second vaccine (p = 0.02 vs 1st vaccine). NK cells continued to produce high levels of IFN-g in response to and at the end of treatment (P = 0.004, responders vs non-responders). CD8+ T cells underwent a rapid expansion and produced higher levels of IFN-γ compared to baseline (p < 0.02), but after the first administration of adjuvant TMZ primed CD8+ T cells failed to form an effector memory phenotype (CCR7negCD45RAnegCD62Llow/neg).We also studied in human PBL the expression of the multidrug-resistance protein Abcc3, conferring chemotherapy resistance to murine NK cells. Using Real Time-PCR, Abcc3 expression was found higher in responders vs non-responders before and after radiochemotherapy (p = 0.0005 and p = 0.02, respectively) and during vaccination and adjuvant TMZ (p < 0.01). Conclusions: These findings demonstrate that in DENDR-I patients with longer PFS DC vaccinations increase the number of active NK cells and the expression of Abcc3 and suggest that adjuvant chemotherapy interferes with effector memory formation.
One-Time Administration of Recombinant Human Erythropoietin Decreases B Cell in Human Peripheral Blood
Authors: Tomomi Nagashima, Akihiko Yokohama, Kie Nagai, Rumi Ino, Noriyuki Takahashi, Tetsuhiro Kasamatsu, Tomomi Sekigami, Hirono Iriuchishima, Makiko Takizawa, Hiroshi Handa, Takayuki Saitoh, Hirokazu Murakami
Journal: Blood (2016)
Internet-Based Self-help Interventions for Depression in Routine Care
Authors: David Daniel Ebert, Harald Baumeister
Journal: JAMA Psychiatry (2017)

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Systematic determination of microRNAs associated with chemosensitivity of 5-fluorouracil, CPT-11, and oxaliplatin in colorectal cancer
Authors: Yaguang Xi, Jingfang Ju
Journal: Clinical Cancer Research (2007)

B13   Background: Non-coding small microRNAs (miRNAs) regulate gene expression at the posttranscriptional and translational level and altered miRNA expression has been linked to tumorigenesis. Previous studies from our laboratory have shown that tumor suppressor p53 mediated a number of miRNAs expression and several of these miRNAs were associated with patient’s response and survival in colorectal cancer. In this study, the involvement of miRNAs in chemosentitivity of several anticancer agents was systematically determined using miRNA expression profiling approach. Materials and Methods: We systematically examined the expression changes of miRNAs in response to genotoxic stress including 5-Fluorouracil (5-FU), CPT-11, and Oxaliplatin in human colon cancer HCT-116 (wt-p53) and HCT-116 (null-p53) cells. The miRNA expression profiles were quantified by miRCURY Locked Nucleic Acid (LNA) array analysis. ImaGene 7.0 and GeneSpring 7.2 Software were employed for data analysis with 2-fold cut-off for expression threshold. The impact of certain miRNAs on chemosensitivity was characterized based on the overexpression of miRNAs and the LD-50 changes were quantified using XTT assays. Results: Differential miRNA expression profiles related to chemosensitivity were discovered by comparing the profiles of miRNAs between HCT-116 (wt-p53) and HCT-116 (null-p53) cells treated with three different anticancer agents. The expression of 101 miRNAs was altered in response to 5-FU, 60 miRNAs were involved in CPT-11 treatment and 64 differentially regulated miRNAs were associated with Oxaliplatin exposure with 2-fold cut-off. Although each genotoxic agent yields unique miRNA expression profiles, there are 29 overlap miRNAs involved in all three different treatments exclusively in HCT-116 (wt-p53) cells. Some of them had been validated and determined to be related to chemosensitivity.  Conclusion: This study provides a comprehensive understanding of miRNAs involved in response to several key anticancer agents in colorectal cancer. Some of them may become potential novel targets to overcome chemoresistance and benefit the personalized treatment in the colorectal cancer.
SPORTS-RELATED ELBOW ULNAR COLLATERAL LIGAMENT INJURY IN THE 21ST CENTURY
Authors: Jason Zaremski, JoAnna McClelland, Heather Vincent, Kevin Vincent, Daniel Herman, Michael Seth Smith, Bryan Prine, Kevin Farmer, Michael Moser, MaryBeth Horodyski
Journal: British Journal of Sports Medicine (2017)

<h3>Background</h3> Elbow ulnar collateral ligament (UCL) injuries are common injuries in adolescent athletes, particularly overhead athletes. Surgical UCL incidence and outcomes are well-researched, but non-surgical UCL injury patterns and management in developing athletes are not clear. <h3>Objective</h3> To determine patterns of UCL injuries among competitive athletes aged 11–22 years. We hypothesized that non-surgical UCL injuries occurred more frequently in younger athletes during the time frame of 2000–2016. <h3>Design</h3> Descriptive epidemiological study. <h3>Setting</h3> Academic, tertiary medical center. <h3>Patients (or Participants)</h3> Electronic medical records and key word searches were used to identify patients with UCL injuries sustained during competitive athletics (N=136). <h3>Interventions (or Assessment of Risk Factors)</h3> Age, time of injury by year, sport classification, sex. <h3>Main Outcome Measurements</h3> UCL injuries and severity; injury management (surgical, non-surgical). <h3>Results</h3> There were 53 surgical and 83 non-surgical UCL injuries. Non-surgical cases increased nine-fold from 2009–2016 compared to 2000–2008. Injury distribution was as follows: 60 sprains, 39 partial tears, 36 ruptures, 1 re-rupture. 92% of sprains did not undergo surgical intervention, whereas 51% of partial tears and 78% of ruptures underwent UCL-Reconstruction (UCL-R). There are increasing numbers of UCL injuries with increasing age; X<sup>2</sup> (4,136)=14.209, p=0.007. Non-surgical UCL injuries occurred in highest frequency in the youngest athletes (100% of total injuries in 11–13 years; 71.4% of 14–16 years; 44.3% of 17–22 years). UCL injury volume was most commonly associated with the sports baseball (OR 1.55, p=0.32; 95% CI 0.69–3.51), softball (OR 0.76, P=0.76, 95% CI 0.22 to 2.68), American football (OR 0.50, p=0.48; 95% CI 0.10–2.59, and javelin (OR 6.69, p=0.07; 95% CI 0.72–61.62). <h3>Conclusions</h3> Younger athletes are sustaining more frequent, less severe UCL injuries. Enforcement of appropriate rest, proper sport-related mechanics and diversifying sport participation are important to prevent a) UCL injury at a young age, and b) progression of a non-surgical injury to a potential UCL-R.
Are racial differences in obesity and insulin resistance related to aggressive breast cancer?
Authors: Emily Gallagher, Derek Leroith, Sheldon M. Feldman, Elisa R. Port, Neil Friedman, Melissa Louise Pilewskie, Alison Estabrook, Susan K. Boolbol, Rebeca Franco, Kezhen Fei, Nina A. Bickell
Journal: Journal of Clinical Oncology (2016)

1568 Background: Black women are more likely to die of breast cancer and have more aggressive type cancers than white women. Black women are also more likely to have obesity and insulin resistance than white women. Insulin resistance has been associated with faster tumor growth in mouse models of breast cancer, but has not been studied as a potential mediator of racial disparities in women with breast cancer. We hypothesized that black women would have more aggressive breast cancer at presentation and this would be associated with obesity and insulin resistance. Methods: We recruited 281 (80% white, 20% black) women with a new primary breast cancer and measured pre-operative fasting blood glucose and insulin, BMI, waist circumference (WC), Nottingham prognostic index (NPI). We classified aggressive breast cancer as a NPI > 4.4. We calculated HOMA-IR (HOMA) scores and classified insulin resistance a HOMA > 2.8, the upper quartile of insulin resistance in the US population. Patients self-identified race. Results: Of 281 women with new breast cancer, average age was 58 years (SD = 12.5). 181 (64%) were stage I; 89 (32%) stage II; 11 (4%) stage III at time of diagnosis. Seventeen percent of cancers had an NPI > 4.4. There was no racial difference in stage or aggressive breast cancer: 22% of blacks vs. 16% of whites (p = 0.3) had cancers with NPI > 4.4. Eight percent of women were insulin resistant: 11% blacks vs. 7% whites (p = 0.4). There were also racial differences in BMI (32.3 in B vs. 26.0 in W; p < .0001), WC (110cm in B vs 94cm in W, p < 0.001), HOMA score (1.7 in B vs.1.2 vs W; p = 0.002), NPI score (4.0 in B vs. 3.6 in W, p = 0.01) and triple negative breast cancer (15% in B vs 6% in W, p = 0.04). HOMA score was positively associated with NPI score (r = 0.18; p = 0.02). HOMA_IR partially mediates the effect of black race with more aggressive cancer (β = 0.07; 95%CI: 0.02-0.15). Conclusions: Among women with newly diagnosed breast cancer, insulin resistance partially mediates the relationship between black race with more aggressive cancer suggesting that hyperinsulinemia may promote breast cancer progression and contribute to racial disparities in breast cancer survival.
Abstract 367: Lysyl Oxidase Expression by Cardiac Fibroblasts is Regulated by Integrin-mediated Signaling
Authors: Albert Gao, Lauren D Black
Journal: Circulation Research (2015)

Cardiac fibrosis following myocardial infarction (MI) leads to reduced cardiac function, and contributes to heart failure and mortality. Recent studies shown the extent of adverse remodeling may be mitigated by therapeutic strategies which regulate cardiac fibroblast mediated-remodeling. Since cross-linking by lysyl oxidase (LOX) increases following MI and alters the mechanical properties of the infarct, it is critical to characterize how its expression is regulated by CFs post-MI. While LOX expression is attributable to TGF-β1 signaling, we hypothesize that changes in the stiffness and composition of the ECM can also alter LOX expression via integrin-mediated signaling. To investigate this, we isolated CFs from healthy left ventricle (LV) and infarcted cardiac fibroblasts (ICFs) from 1 week post-MI LV and cultured them on tissue culture plastic (TCP) and collagen I-coated plates (COL) in serum-free media for 48 hours to assess the expression of genes associated with LOX signaling, fibrosis, and myofibroblast activation. Our results show an upregulation of LOX gene expression in both CFs and ICFs when cultured on COL and this is further emphasized with the presence of TGF-β1 (Fig. 1A). Gene expression of col1α1, integrin β1 subunit and αSMA (Fig. 1B-D) also exhibit similar upregulation. Ongoing studies will investigate how altered substrate stiffness and composition affect gene expression of LOX and other genes associated with fibrosis. By understanding the effect of the physical microenvironment on the expression of fibrotic genes including LOX, we aim to develop novel therapeutic strategies to attenuate cardiac fibrosis and thus improve cardiac recovery following MI.
Pilot study of T cells redirected to EGFRvIII with a chimeric antigen receptor in patients with EGFRvIII+ glioblastoma.
Authors: Donald M. O'Rourke, MacLean Nasrallah, Jennifer J. Morrissette, Jan J. Melenhorst, Simon F. Lacey, Keith Mansfield, Maria Martinez-Lage, Arati Suvas Desai, Steven Brem, Eileen Maloney, Suyash Mohan, Sumei Wang, Gaurav Verma, Jean-Marc Navenot, Angela Shen, Zhaohui Zheng, Bruce Levine, Hideho Okada, Carl H. June, Marcela Valderrama Maus
Journal: Journal of Clinical Oncology (2016)

2067 Background: We have developed an autologous T cell product directed to the EGFR variant III mutation via lentiviral transduction of a chimeric antigen receptor (CAR), and opened an IND. We have initiated a pilot study enrolling patients with recurrent EGFRvIII-positive glioblastoma (GBM). Methods: Patients with recurrent GBM have their tumors screened for the presence of the EGFRvIII mutation by a next-generation sequencing based assay. Eligible patients undergo leukapheresis for collection of autologous T cells, which are genetically modified ex vivo to express the EGFRvIII CAR, expanded, and then cryopreserved for infusion. Results: We report results on the nine patients we have treated. To date, we have found that infusion of 1-5x108 CART-EGFRvIII cells is feasible to manufacture and infusion is safe, without evidence of off-tumor toxicity or cross-reactivity to wild type EGFR. No clinical or laboratory signs of systemic cytokine release syndrome have been observed, though elevations in serum IL-6 occur concurrently with CART-EGFRvIII expansion in the peripheral blood. One patient developed non-convulsive status epilepticus nine days after CART-EGFRvIII infusion, which resolved with standard treatment and anti-cytokine therapy. All patients have had significant expansion of CART-EGFRvIII cells between 7-10 days post-infusion, as measured by flow cytometry and quantitative PCR in peripheral blood samples. Five patients have undergone surgical resection of tumor between 6-120 days after infusion, and pathologic evaluation has demonstrated infiltration of activated CAR T cells, recruitment of new T cells (as assessed by next generation T cell receptor deep sequencing), and specific EGFRvIII target antigen loss in GBM cells in some cases. Conclusions: These findings provide evidence that CART-EGFRvIII cells are safe, without evidence of off-target toxicity or cytokine release syndrome, and are immunologically active. The data also suggest a mechanism of antigen editing by activated CART-EGFRvIII cells that track to specific EGFRvIII GBM cells. Clinical trial information: NCT02209376.
Pancreatico-gastrostomie guidée par échoendoscopie. Résultats chez 10 patients
Authors: M Giovannini, J Devière, E Bories, CH Pesenti, JR Delpero
Journal: Endoscopy (2005)

But Nous rapportons une nouvelle technique d'échoendoscopie interventionnelle qui consiste à créer une communication entre le canal de wirsung et l'estomac représentant une alternative à l'anastomose wirsugo-jéjunale chirurgicale.
Risk evaluation about genetic screening among ovary cancer with regard to Lynch syndrome.
Authors: Min Kyu Kim
Journal: Journal of Clinical Oncology (2017)

e13000 Background: Hereditary cancer syndrome about ovary cancer is mostly BRCA related. But mismatch repair genes related Lynch syndrome is also associated with it.There is not much study about risk evaluation about this among Korean population. We investigate this. Methods: A retrospective review of ovary cancer patients who was counseled about Lynch syndrome in Department of Obstetrics and gynecology, Samsung Changwon Hospital by single surgeon was done. Clinical information was extracted from the medical record including age, family and personal history of cancer, immunohistochemistry (IHC) of MLH1/MSH2, microsatellite instability test (MSI). Results: Total test was 26.mean age was 54(16~75) and fifty percent was serous type (13/26).There were 2 patients with Lynch syndrome related cancer family history (stomach and ovary) among their 1 st degree relatives. Only one patient has abnormal MLH1 IHC.There were three unstable MSI patients (BAT26, D2S123, D55346, and NR21). Conclusions: We found three abnormal MSI patients among this population. Cost effective algorithm using multiple genetic testing to find Lynch syndrome associated ovary cancer patients should be developed through large population study.
The Relationship of Serum Soluble Receptor for Advanced Glycation End Products (sRAGE) and Carboxymethyl Lysine (CML) to the Incidence of Diabetic Nephropathy in Persons With Type 1 Diabetes
Authors: Ronald Klein, Kayla Horak, Kristine E. Lee, Lorraine Danforth, Karen J. Cruickshanks, Michael Y. Tsai, Ronald E. Gangnon, Barbara E.K. Klein
Journal: Diabetes Care (2017)

We hypothesized that persons with type 1 diabetes with higher serum levels of carboxymethyl lysine (CML) and soluble receptor for advanced glycation end products (sRAGE) are at a higher risk of developing incident diabetic nephropathy (DN). We examined this hypothesis using data from up to four follow-up examinations over a 22-year period in persons with type 1 diabetes participating in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). We also examined the relationship of CML and sRAGE to mortality.

Descriptions of the cohort, participation statistics, and reasons for nonparticipation have appeared elsewhere (1). Of 1,210 persons with type 1 diabetes receiving care in an 11-county area of south central Wisconsin in 1979–1980, 996 were examined in 1980–1982. The individuals were 3–79 years of age with type 1 diabetes duration of 1–59 years. These persons participated in up to six follow-up examinations in 1984–1986 ( n = 903), 1990–1992 ( n = 816), 1994–1996 ( n = 667), 2000–2001 ( n = 567), 2005–2007 ( n = 520), and 2012–2014 ( n = 414).

The tenets of the Declaration of Helsinki were followed, and institutional review board approval was obtained from the University of Wisconsin–Madison. Written informed consent was obtained.

Starting with the third examination in 1990–1992 and continuing with follow-up examinations, serum was collected, processed, and frozen at −80°C. Serum sRAGE and CML levels were measured …
David Oliver: Towards a GP consensus on the future of UK general practice
Authors: David Oliver
Journal: BMJ (2017)

As a hospital doctor, I rarely write about general practice unless it’s to defend, celebrate, or support it. Primary care is the engine room of the NHS and underpins its equity, efficiency, and access. But it’s underfunded, understaffed, and overstretched by rising demand.1

I’m breaking my “no primary care columns” rule and asking where GPs themselves think that UK general practice should go next. I speak to and read pieces by many GPs, and I see universal agreement that general practice needs better funding and staffing. I admired the clarity of the Royal College of General Practitioners’ paper on The 2022 GP: a Vision for General Practice in the Future NHS 2 and have been enlightened by many of the college’s campaigns …