tbuckley/cabot-search huggingface dataset:
Abstract 15584: Exercise Training Improves Left Ventricular Remodeling via Increase of the CD4+CD25+Foxp3+ Regulatory T Cells in Murine Heart Failure After Myocardial Infarction
Authors: Akiyo Eguchi, Toshihiro Iwasaku, Yoshitaka Okuhara, Makiko Oboshi, Yoshiro Naito, Toshiaki Mano, Tohru Masuyama, Shinichi Hirotani
Journal: Circulation (2016)

Background:  Myocardial remodeling after myocardial infarction (MI) causes heart failure. CD4+CD25+Foxp3+ regulatory T cells (Treg cells) have protective effects in wound healing and adverse ventricular remodeling after MI. Repeated aerobic exercises enhance Treg cell responses in animal studies. Repeated aerobic exercises also reduce myocardial remodeling after MI. Therefore, we hypothesized that repeated aerobic exercise training enhances Treg cell responses and reduces myocardial remodeling after MI.   Methods:  Fourteen days after ligating the left anterior descending coronary artery, mice were randomly assigned two groups, exercise training group (ETG) and non-exercise training group (NTG). In ETG, mice performed swimming exercise training for ninety minutes twice a day for four weeks. After four weeks of training, mice were sacrificed, and cardiac histology and cardiac mRNA expression were examined. The number of Tregs (CD4+CD25+Foxp3+) was determined by flow cytometry in peripheral blood.   Results:  Four weeks after exercise training, heart weight (HW)/tibia length (TL) and lung W (LW)/TL were significantly lower in ETG than those in NTG (HW/TL; 9.7 ± 0.4 vs. 12.1 ± 0.3 p    Conclusion:  Exercise training decreased lung congestion and reduced fibrosis and myocardial remodeling after MI. Furthermore, exercise training increased the number of Treg cells in blood and decreased serum TNF-α and IL-6. Exercise training reduced myocardial remodeling, maybe thorough upregulation of Treg.
Expression of hTERT in Gastrointestinal Stromal Tumours Occurs Preferentially in Malignant Neoplasms
Authors: M Sabah, R Cummins, M Leader, E Kay
Journal: Endoscopy (2006)

Aims: The objective of this study was to evaluate the expression of human telomerase reverse transcriptase (hTERT) in gastrointestinal stromal tumours (GISTs).
Abstract 20: Resident Cardiac Stem Cell Growth Determines the Number of Ventricular Cardiomyocytes in the Mouse Heart
Authors: Barbara Ogórek, João Ferreira-Martins, Donato Cappetta, Alex Matsuda, Sergio Signore, Domenico D'Amario, James Kostyla, Elisabeth Steadman, Virginia Caballero, Noriko Ide-Iwata, Fumihiro Sanada, Toru Hosoda, Piero Anversa, Annarosa Leri, Marcello Rota, Jan Kajstura
Journal: Circulation Research (2012)

The objective of this study was to determine the role of c-kit-positive cardiac stem cells (CSCs) in the formation of the heart during prenatal life, and immediately after birth. Mice in which EGFP is under the control of the c-kit-promoter were employed to measure the number of CSCs (Ns), the fraction of cycling MCM5-positive CSCs (f) and the length of the cell cycle (Ts) in CSCs. The number of CSCs committed to the myocyte lineage (LCC: lineage committed cells) included myocyte progenitors (c-kit-positive, Nkx2.5-positive cells), myocyte precursors (c-kit-positive, Nkx2.5-positive, and α-sarcomeric actin-positive cells) and replicating amplifying myocytes (c-kit-negative, Nkx2.5-positive, α-sarcomeric actin-positive, and MCM5-positive cells). These variables derived from CSC growth and lineage specification were evaluated to define the rate of formation of terminally differentiated myocytes (r). Based on a hierarchically structured cell organization, the rate of entry (Rs) of CSCs into the cell cycle was computed from Rs = f x (Ns/Ts), and the rate of generation of mature myocytes, r, was obtained from r = Rs x 2 Gt = ((f x Ns)/Ts) x 2 Gt . The exponent Gt defines the number of transit generations, i.e., the number of divisions that one CSC has to go through before it acquires the terminally differentiated myocyte phenotype. To validate this scenario and establish the number of post-mitotic myocytes formed, the primary data listed above were collected at E9, E14, E19 and P1. The number of mature cardiomyocytes generated by 1 CSC in 1 day was 1.1 x 10 3 , 20 x 10 3 , 501 x 10 3 , and 440 x 10 3 at E9, E14, E19 and P1, respectively. The total number of myocytes (Nm) formed from E9 to E14, E19 and P1 was derived from an exponential equation with the best fit to the experimental data: Nm = exp (0.69 x t) where Nm is the number of myocytes and t is time in days. Accordingly, CSCs generated 1 x 10 5 , 1 x 10 6 and 1.8 x 10 6 myocytes at from E9 to E14, E19 and P1, respectively. These values accounted for all parenchymal cells present at mid and late gestation and in the neonatal heart measured morphometrically. Thus, the expansion of the myocyte mass during embryonic, fetal and immediate postnatal development is controlled by activation, growth and differentiation of resident c-kit-positive CSCs.
Impaired calcium homeostasis is associated with sudden cardiac death and arrhythmias in a genetic equivalent mouse model of the human HRC-Ser96Ala variant
Authors: Christos Tzimas, Daniel M Johnson, Demetrio J Santiago, Elizabeth Vafiadaki, Demetrios A Arvanitis, Constantinos H Davos, Aimilia Varela, Nikolaos C Athanasiadis, Constantinos Dimitriou, Michalis Katsimpoulas, Stephan Sonntag, Mariya Kryzhanovska, Doron Shmerling, Stephan E Lehnart, Karin R Sipido, Evangelia G Kranias, Despina Sanoudou
Journal: Cardiovascular Research (2017)

The histidine-rich calcium-binding protein (HRC) Ser96Ala variant has previously been identified as a potential biomarker for ventricular arrhythmias and sudden cardiac death in patients with idiopathic dilated cardiomyopathy. Herein, the role of this variant in cardiac pathophysiology is delineated through a novel mouse model, carrying the human mutation in the homologous mouse position. The mouse HRC serine 81, homologous to human HRC serine 96, was mutated to alanine, using knock-in gene targeting. The HRC-Ser81Ala mice presented increased mortality in the absence of structural or histological abnormalities, indicating that early death may be arrhythmia-related. Indeed, under stress-but not baseline-conditions, the HRC-Ser81Ala mice developed ventricular arrhythmias, whilst at the cardiomyocyte level they exhibited increased occurrence of triggered activity. Cardiac contraction was decreased in vivo, ex vivo, and in vitro. Additionally, Ca2+ transients and SR Ca2+ load were both reduced suggesting that cytosolic Ca2+ overload is not the underlying proarrhythmic mechanism. Interestingly, total SR Ca2+ leak was increased in HRC-Ser81Ala cardiomyocytes, without an increase in Ca2+ spark and wave frequency. However, Ca2+ wave propagation was significantly slower and the duration of the associated Na/Ca exchange current was increased. Moreover, action potential duration was also increased. Notably, Ca2+/Calmodulin kinase II (CaMKII) phosphorylation of the ryanodine receptor was increased, whilst KN-93, an inhibitor of CaMKII, reduced the occurrence of arrhythmias. The homologous mutation Ser81Ala in HRC in mice, corresponding to Ser96Ala in humans, is associated with sudden death and depressed cardiac function. Ventricular arrhythmias are related to abnormal Ca2+ cycling across the SR. The data further support a role for CaMKII with the perspective to treat arrhythmias through CaMKII inhibition.
Combination Therapy with NHS-muIL12 and Avelumab (anti-PD-L1) Enhances Antitumor Efficacy in Preclinical Cancer Models
Authors: Chunxiao Xu, Yanping Zhang, P. Alexander Rolfe, Vivian M. Hernández, Wilson Guzman, Giorgio Kradjian, Bo Marelli, Guozhong Qin, Jin Qi, Hong Wang, Huakui Yu, Robert Tighe, Kin-Ming Lo, Jessie M. English, Laszlo Radvanyi, Yan Lan
Journal: Clinical Cancer Research (2017)

Purpose: To determine whether combination therapy with NHS-muIL12 and the anti-programmed death ligand 1 (PD-L1) antibody avelumab can enhance antitumor efficacy in preclinical models relative to monotherapies.Experimental Design: BALB/c mice bearing orthotopic EMT-6 mammary tumors and μMt- mice bearing subcutaneous MC38 tumors were treated with NHS-muIL12, avelumab, or combination therapy; tumor growth and survival were assessed. Tumor recurrence following remission and rechallenge was evaluated in EMT-6 tumor-bearing mice. Immune cell populations within spleen and tumors were evaluated by FACS and IHC. Immune gene expression in tumor tissue was profiled by NanoString® assay and plasma cytokine levels were determined by multiplex cytokine assay. The frequency of tumor antigen-reactive IFNγ-producing CD8+ T cells was evaluated by ELISpot assay.Results: NHS-muIL12 and avelumab combination therapy enhanced antitumor efficacy relative to either monotherapy in both tumor models. Most EMT-6 tumor-bearing mice treated with combination therapy had complete tumor regression. Combination therapy also induced the generation of tumor-specific immune memory, as demonstrated by protection against tumor rechallenge and induction of effector and memory T cells. Combination therapy enhanced cytotoxic NK and CD8+ T-cell proliferation and T-bet expression, whereas NHS-muIL12 monotherapy induced CD8+ T-cell infiltration into the tumor. Combination therapy also enhanced plasma cytokine levels and stimulated expression of a greater number of innate and adaptive immune genes compared with either monotherapy.Conclusions: These data indicate that combination therapy with NHS-muIL12 and avelumab increased antitumor efficacy in preclinical models, and suggest that combining NHS-IL12 and avelumab may be a promising approach to treating patients with solid tumors. Clin Cancer Res; 23(19); 5869-80. ©2017 AACR.
Glycosylation and Golgi Apparatus Structural Integrity are Essential in Targeting GLUT-1 to Membranes of Colorectal Cancer Cells
Authors: S Bakhiet, M Izzuan, M Tosetto, H Mulcahy, D O'Donoghue, K Sheahan, J O'Sullivan
Journal: Endoscopy (2006)

Background: GLUT-1 is a high affinity glucose transporter up-regulated at cancer cell membranes. Factors involved in targeting GLUT-1 to membranes are not understood in colorectal cancer.
ATP and cough reflex hypersensitivity: a confusion of goals?
Authors: Helen Elizabeth Fowles, Tim Rowland, Caroline Wright, Alyn Morice
Journal: European Respiratory Journal (2017)

We thank our friends M.G. Belvisi and J.A. Smith for their interest in our article. We are in agreement that cough hypersensitivity syndrome (CHS) is a clinical diagnosis, currently without a firm pathophysiological explanation. The exquisite sensitivity of patients with CHS to a wide variety of irritants is attested in every clinic and is a cardinal feature of the clinical history of this condition. The stunning effectiveness of AF-219/MK-7264 in chronic cough led us to the assumption that ATP inhalation may well be the physiological tool to define CHS just as methacholine hyperresponsiveness is useful in defining the phenomenon of bronchial hyperresponsiveness. Sadly, our results did not confirm this expectation. Our patients were not "uncharacterised" but had been through our well-established clinic protocol. They were entirely typical of chronic cough patients. The failure of ATP challenge to demonstrate a marked leftward shift in the concentration response curve in chronic cough is puzzling, but we have difficulty understanding M.G. Belvisi and J.A. Smith's alternative explanation. AF-219/MK-7264 is thought to have a mainly peripheral activity; however, the periphery will also include the nodose and jugular ganglia of the vagus nerve, where phenotypic switching has been well described [1]. Our observation that hypersensitivity in chronic cough was no more demonstrated by ATP than citric acid or capsaicin does, to us, suggest that this phenomenon resides not on the nerve terminals where we had for many years assumed it to be, but rather be part of a pan-neuronal phenomenon. Cough hypersensitivity is a mystery that continues to require unravelling <http://ow.ly/Fhel30cgA5u>
XIAP is highly expressed in melanoma and is associated with chemotherapy resistance
Authors: H. M. Kluger, M. McCarthy, A. Alvero, K. Divito, R. Camp, D. Rimm, G. Mor
Journal: Journal of Clinical Oncology (2006)

8008 Background: Chemoresistance is a major problem in treating melanoma. The X-linked inhibitor of apoptosis (XIAP) is associated with chemoresistance in other cancers. Here we characterize XIAP expression in primary and metastatic melanomas and determine whether XIAP plays a role in chemoresistance. We report differential expression of XIAP between primary and metastatic melanomas and benign nevi. We demonstrate that inhibition of XIAP expression by Phenoxodiol can reverse chemoresistance. Methods: We employed tissue microarrays containing specimens from 548 melanoma patients and 540 benign nevi. XIAP expression was evaluated by an automated method for in situ quantitative analysis of protein levels (AQUA). We use S100 to define pixels as melanoma (tumor mask) within the array spot, and measure intensity of XIAP expression using Cy5 conjugated antibodies within the mask. AQUA scores were correlated with clinical and pathological variables. Cell viability after exposure to Carboplatin and Phenoxodiol was determined in 3 melanoma cell strains using the CellTiter 96 Assay. Apoptosis was measured using the Caspase-3/7 GloTM Assay, and levels of XIAP and Caspase 2 were assessed by Western blots. Results: XIAP expression was significantly higher in melanomas than in nevi (P&lt;0.0001), and higher in metastatic than in primary specimens (P&lt;0.0001). All three melanoma cell strains examined were highly resistant to Carboplatin, and moderately resistant to Phenoxodiol. Pre-treatment with Phenoxodiol prior to Carboplatin induced a significant decrease in XIAP expression, which correlated with remarkable sensitization to Carboplatin. Conclusions: XIAP expression is higher in malignant melanocytes than in their benign counterparts. Expression is higher in early stage disease specimens than in metastatic specimens, suggesting an association with disease aggression. Phenoxodiol is a well tolerated drug, and has been shown to inhibit XIAP expression in ovarian cancer. Here we demonstrate that melanoma is resistant to Carboplatin, possibly due to XIAP expression. In vitro inhibition of XIAP by Phenoxodiol sensitizes melanoma cells to Carboplatin. This drug combination warrants further investigation as a therapeutic approach for metastatic melanoma. [Table: see text]
Pomalidomide with Low Dose Dexamethasone Is Effective Irrespective of Primary or Secondary Resistance to Lenalidomide but the IMiD-Free Interval Is Important
Authors: Meletios A Dimopoulos, Maria Roussou, Nikolaos Kanellias, Maria Gavriatopoulou, Magdalini Migkou, Ioannis Panagiotidis, Evangelos Eleutherakis-Papaiakovou, Dimitrios Ziogas, Despina Fotiou, Stavroula Giannouli, Panagiotis Tsirigotis, Christos Poziopoulos, Sossana Delimpasi, Despoina Mparmparoussi, Charis Matsouka, Kostas Konstantopoulos, Evangelos Terpos, Efstathios Kastritis
Journal: Blood (2016)
Complete clinical (CC) responders to definite chemoradiation or radiation therapy (CRT/RT) for esophageal cancer (EC): A survival analysis.
Authors: Xavier Mirabel, Emmanuelle Tresch, Olivier Romano, Sylvain Dewas, Eric Amela, Charles Fournier, Stephanie Clisant, Christophe Mariette, Antoine Adenis
Journal: Journal of Clinical Oncology (2012)

e14560 Background: For pts with EC being treated with definite CRT/RT, predictors of outcome are baseline nutritional status and CC response to CRT. As data concerning predictors of outcome for CC responders are lacking, we tried to identify them. Methods: Among 402 consecutive pts with EC who underwent definite CRT/RT in our institution from 1/1998 to 12/2003, 110 were found CC responders, and were retrospectively reviewed. Baseline staging included endoscopy with biopsies, and CT-scan and/or EUS. CC responders were defined as pts without evidence of tumor on morphological examination with biopsies, 4 to 6 weeks after treatment. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. Results: Pts were staged according to EUS-AJCC staging (stage I-II=39, stage III-IVa=37, ukn=34) and/or CT staging (stage I-II=54, stage III-IVa=32, ukn=24). Baseline pt and tumor characteristics were as follows: M/F = 98/12, median age = 60, ADK/SCC = 7/103, tumor site (upper/middle/lower third) = 41/50/19, weight loss none/&lt;10%/≥10% = 36/45/29, dysphagia gr.0/1/≥2 = 30/14/65. Pts received a median dose of RT of 50.4Gy (30-65), and concomitant chemotherapy in 95/110 cases. Post treatment nutritional characteristics were : weight loss during treatment none/&lt;10%≥10% = 35/38/37, remaining dysphagia gr.0/1/≥2 = 54/24/32. During follow up (median: 6 [0.4-9.8] years), 16 pts got esophagectomy (recurrence: 3, some reasons: 13). Median survival was 2.5 years, and 3- and 5-year survival rates were 46.9%, and 33.5%, respectively. Neither TNM classification nor stage grouping, histological type, gender, or treatment types were found to have any influence on outcome. Predictors of improved OS were: absence of weight loss during treatment, and absence of dysphagia with normal oral intakes after treatment. Conclusions: One EC pt out of 3 with CC response after definite CRT/RT is still alive at 5 years. The absence of weight loss during treatment, and of remaining dysphagia after treatment are significant predictors of better survival in pts found CC responders to definite CRT/RT for EC.
First Description of Retrograde Balloon Dilatation of the Cardia of Achalasia Using the Retroflexed Gastroscope – Technique and Early Clinical Experience
Authors: T Murphy, M O'Sullivan, M Buckley, G O'Sullivan
Journal: Endoscopy (2006)

Although oesophagomyotomy provides the best long-term results for achalasia, pneumatic balloon dilation of the cardia is the preferred treatment modality for many patients. For optimal dilation a 3–4cm balloon is usually positioned across the cardia under radiographic control.
BMA annual meeting: Senior trainees will be balloted on new consultant contract, says BMA
Authors: Tom Moberly
Journal: BMJ (2017)

Senior trainees, as well as all consultants, will be balloted on proposals for a new consultant contract, the BMA has said.

Delegates at the BMA’s annual representative meeting (ARM) in Bournemouth on 29 June voted in favour of a motion which said that “all consultants, [BMA] members on the specialist register, and junior doctors of year three specialty training and above should be balloted on the new consultant contract proposals.”

The motion, which was subject to an electronic vote at the conference, was passed by 116 votes to 89 (57% for the motion, 43% against).

Earlier …
Increasing use of allogeneic hematopoietic cell transplantation in patients aged 70 years and older in the United States
Authors: Lori Muffly, Marcelo C. Pasquini, Michael Martens, Ruta Brazauskas, Xiaochun Zhu, Kehinde Adekola, Mahmoud Aljurf, Karen K. Ballen, Ashish Bajel, Frederic Baron, Minoo Battiwalla, Amer Beitinjaneh, Jean-Yves Cahn, Mathew Carabasi, Yi-Bin Chen, Saurabh Chhabra, Stefan Ciurea, Edward Copelan, Anita D’Souza, John Edwards, James Foran, Cesar O. Freytes, Henry C. Fung, Robert Peter Gale, Sergio Giralt, Shahrukh K. Hashmi, Gerhard C. Hildebrandt, Vincent Ho, Ann Jakubowski, Hillard Lazarus, Marlise R. Luskin, Rodrigo Martino, Richard Maziarz, Philip McCarthy, Taiga Nishihori, Rebecca Olin, Richard F. Olsson, Attaphol Pawarode, Edward Peres, Andrew R. Rezvani, David Rizzieri, Bipin N. Savani, Harry C. Schouten, Mitchell Sabloff, Matthew Seftel, Sachiko Seo, Mohamed L. Sorror, Jeff Szer, Baldeep M. Wirk, William A. Wood, Andrew Artz
Journal: Blood (2017)
Prenatally Diagnosed Trisomy 21—Reply
Authors: Amanda Davis
Journal: JAMA Pediatrics (2017)

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
NGS to reveal heterogeneity between cerebrospinal fluid and plasma ctDNA among non-small cell lung cancer patients with leptomeningeal carcinomatosis.
Authors: Ben-Yuan Jiang, Yangsi LI, Shaokun Chuai, Zhou Zhang, Jin-Ji Yang, Wenzhao Zhong, Qing Zhou, Yi-Long Wu
Journal: Journal of Clinical Oncology (2017)

9022 Background: In current clinical setting, NSCLC patients harboring specific driver mutation were usually treated guiding by prior profiling of the primary tumor when developed to brain metastasis. Some studies have shown that circulating tumor DNA (ctDNA) derived from cerebrospinal fluid (CSF) can reveal unique genomic alterations present in brain malignancies. We assessed CSF as a liquid biopsy media and compared to matched plasma. Methods: We performed capture-based ultra deep sequencing on ctDNA derived from matched CSF, plasma of 40 non-small cell lung cancer (NSCLC) patients with suspected leptomeningeal carcinomatosis (LC) using a panel consisting of 168 genes. Results: Among the 40 suspected LC cases, 35 were confirmed to have LC, ctDNA in CSF from the 5 non-LC cases are all undetectable. Circulating tumor DNA was detected in 93.8% of CSF and 66.7% of plasma. We compared mutation profiles and identified 86 and 46 SNVs from CSF and plasma, respectively, with 42 SNVs overlapping. Furthermore, ctDNA from CSF revealed many copy number variations (CNVs) that were not detected from plasma (189 CNVs vs. 3 CNVs). The average maximum allelic fraction (AF) of CSF ctDNA is significantly higher than in plasma (56.7% vs. 4.4% p &lt; 10^-6). Twenty-eight patients were pre-treated with EGFR-TKIs and developed subsequent resistance. EGFR T790M and MET amplification were detected in 21% and 39% in CSF, respectively, showing a unique resistance profile among leptomeningeal metastases patients compared to the general population. Interestingly, 60% of CSF samples harbor TP53 loss of heterozygosity, only 11% of which were detected in the matched plasma samples. Such heterogeneity may reflect unique biological themes for brain metastatic tumor sub-clones. Furthermore, 26 patients received molecular targeted therapy based on the results from CSF, and 23 reported alleviation of symptoms at subsequent evaluations. Conclusions: Collectively, our data reveal that ctDNA derived from CSF provides a unique and more comprehensive characterization of genomic alterations of leptomeningeal carcinomatosis than plasma, supporting the importance of CSF as a liquid biopsy media.