tbuckley/cabot-search huggingface dataset:
Use of Meriva as complementary therapy of locally advanced or metastatic pancreatic cancer (PC) with gemcitabine (GEM).
Authors: Caterina Solda, Cosimo Sperti, Bardini Romeo, Gianfranco Da Dalt, Massimo Gion, Fulvio Ursini, Pasquale Fiduccia, Camillo Aliberti, Davide Pastorelli
Journal: Journal of Clinical Oncology (2016)

e15696 Background: GEM still represents one of the mostly adopted treatments for PC. Combination treatments provided some improvement in response rate (RR) and progression free survival (PFS), although almost invariably associated to increased toxicity. Aiming to find a complementary therapy to GEM in advanced PC, we tested a preparation of curcumin complexed with phospholipids (Meriva) to increase bioavailability. Curcumin has antinflammatory, antioxidant and potential antitumor properties, seemingly, descending from the activation of nuclear factor Nrf2 and inhibition of NFkB. From this pattern of nutraceutical effects of Curcumin, Meriva emerges as a good candidate for complementary therapy, while also improving quality of life (QoL). Methods: This was a single centre, single arm prospective phase II trial. Inclusion criteria were: previously untreated patients with histologically confirmed metastatic or locally advanced PC, ECOG performance status (PS) of 0-2, adequate organ function and written informed consent. Patients received GEM (1,000 mg/mq in 100 minutes on day 1,8,15 every 28 days) and Meriva (2,000 mg/die, continuously) until progression, unacceptable toxicities or refusal. Primary endpoint was RR (according to RECIST 1.1), secondary endpoints were PFS, OS, tolerability and finally QoL. Serum samples collection for inflammatory biomarkers was also performed. Results: Between October 2012 and February 2015 a total of 57 consecutive patients were enrolled. Forty-four patients (15 females and 29 males; 13 locally advanced and 31 metastatic) were suitable for primary endpoint evaluation. Median age was 66 years (range 42-87); all patients except two had ECOG PS 0-1. The median number of treatment cycle was 4.5 (range 2-14). The overall RR was 27,3% (all partial responses), stable disease was reported in 34% of cases with a disease control rate of 61.3%. Grade 3/4 toxicity was observed as neutropenia (7.9%) and anemia (3%). Conclusions: Meriva as complementary therapy to GEM was safe and translate in good disease control rate in first line therapy of advanced PC. Biomarker screening is ongoing to identify patients who get the best benefit from this combination.
Effectiveness of the DECIDE Interventions on Shared Decision Making and Perceived Quality of Care in Behavioral Health With Multicultural Patients
Authors: Margarita Alegria, Ora Nakash, Kirsten Johnson, Andrea Ault-Brutus, Nicholas Carson, Mirko Fillbrunn, Ye Wang, Alice Cheng, Treniece Harris, Antonio Polo, Alisa Lincoln, Elmer Freeman, Benjamin Bostdorf, Marcos Rosenbaum, Claudia Epelbaum, Martin LaRoche, Ebele Okpokwasili-Johnson, MaJose Carrasco, Patrick E. Shrout
Journal: JAMA Psychiatry (2018)

Few randomized clinical trials have been conducted with ethnic/racial minorities to improve shared decision making (SDM) and quality of care.
Frequency Of Anti-inflammatory Related Cutaneous Manifestation In Patients With Aspirin-exacerbated Respiratory Disease (AERD)
Authors: Mayra Coutinho Andrade, Rosilane dos Reis Pacheco, Mila Almeida, Priscila Takejima, Jorge Elias Kalil Filho, Pedro Giavina-Bianchi, Rosana C. Agondi
Journal: Journal of Allergy and Clinical Immunology (2018)
Evaluation prospective de la courbe d'apprentissage de la dissection sous muqueuse gastrique lors de sessions d'entrainement sur modèle porcin vivant
Authors: N Chapelle, N Musquer, D Luet, C Volteau, E Metiver, M Le Rhun, E Coron
Journal: Endoscopy (2018)

La dissection sous muqueuse (DSM), développée et maitrisée depuis longtemps dans les pays asiatiques, est la méthode de choix pour la résection monobloc de lésions tumorales superficielles. Les pays européens rattrapent petit à petit leur retard dans la maîtrise de cette technique. Les recommandations actuelles préconisent un apprentissage multi-étapes de la technique, dont une partie sur modèle animal. L'objectif de notre étude était d'évaluer prospectivement l'efficacité de sessions d'entrainement à la DSM gastrique sur un modèle de cochon vivant anesthésié.
Role of HtrA1 in cell migration and metastasis
Authors: Jeremy Chien, Alfonso Baldi, Giovanni Aletti, Bruno Vincenzi, Ravi Shridhar, Viji Shridhar
Journal: Cancer Research (2007)

LB-274   Metastasis, one of the most significant steps in the progression of cancer, is also the most lethal aspects of cancer. Metastasis and the failure of chemotherapy to treat metastatic disease are the primary causes of cancer-related mortality. One of the critical components in metastasis is the ability of cancer cells to migrate into surrounding tissues and tumor vasculatures. Here we reports that HtrA1, a serine protease previously identified as down-regulated in ovarian cancer and metastatic melanoma, associates with cytoskeletal microtubules, inhibits microtubules assembly, and affects cancer cell motility. HtrA1 localizes to microtubules, and co-precipitates and co-purifies with tubulins. Immunoprecipitation of HtrA1 resulted in co-immunoprecipitation of alpha-, beta-, and gamma-tubulins. Furthermore, purified HtrA1 inhibits in vitro tubulin polymerization. Forced expression of HtrA1 attenuates cancer cell migration, whereas down-regulation of endogenous HtrA1 by RNAi promotes cell motility. Moreover, endogenous HtrA1 inhibits fibronectin-mediated cell spreading without affecting collagen-mediated cell spreading. Finally, immunohistochemical analysis of HtrA1 expression in 67 primary ovarian tumors, 100 primary breast tumors and corresponding 58 nodal metastases, and 100 primary colorectal cancers and corresponding 70 nodal metastases indicates that down-regulation of HtrA1 is associated with metastatic phenotypes of ovarian, breast and colorectal cancers. These results uncover a novel and specific role of HtrA1 in cancer cell migration through its association with cytoskeletal microtubules, and offer initial mechanistic insights into how this protein may modulate cell migration and metastasis.
Abstract 10889: Treating Heart Failure With Preserved Ejection Fraction Through Troponin I Phospho-mimicry
Authors: Maria E Moutsoglou, Gi-Ho Kim, Christopher Solis-Ocampo, Mohit Kumar, Pieter de Tombe, John M Robinson
Journal: Circulation (2015)

Background —Heart failure with preserved ejection fraction (HF-pEF), characterized by resistance to ventricular filling from impaired myofilament relaxation (lusitropy), is the most common variant of heart failure. In HF-pEF, blunting of the lusitropic effect of troponin I (TnI) Ser-23/24 phosphorylation through the β-receptor-cAMP- protein kinase A (PKA) pathway contributes to impaired diastolic relaxation. Methods and Results —To identify small molecule compounds capable of generating the lusitropic effect of PKA-dependent TnI phosphorylation, we developed a 2D in vitro screen, where dye-labeled thin filaments are titrated with Ca 2+ and myosin motors. Thin filament activation is monitored by a FRET assay with FRET donor on the mobile element of TnI and the FRET acceptor on the C-lobe of troponin C (TnC). We observed that full activation of the thin filament required myosin binding. The Ca 2+ -sensitizer bepridil acted as myosin, enhancing thin filament affinity for Ca 2+ and stabilizing the association of the mobile element of TnI with TnC. In the presence of saturating bepridil, adding myosin had no effect on activation, suggesting that bepridil and myosin activate the thin filament through a common mechanism. PKA-treatment decreased the sensitivity of the thin filament to Ca 2+ and to myosin motors, and it reduced the FRET efficiency in the absence of Ca 2+ , suggesting that TnI phosphorylation causes a structural transition in the C-lobe of TnC. Epigallocatechin-3-gallate, the most prevalent polyphenol in green tea, acted as Ser23/24 phospho-TnI, reducing thin filament affinity for Ca 2+ and reducing affinity of myosin for the thin filament under both relaxing and Ca 2+ -activated conditions, suggesting that epigallocatechin-3-gallate and Ser23/24 phospho-TnI relax the myofilament through a common mechanism. Conclusions —Our results suggest that bepridil and myosin activate the cardiac thin filament through a common mechanism while epigallocatechin-3-gallate and Ser23/24 phospho-TnI deactivate the thin filament through a common mechanism. “Myofilament relaxers,” small molecule compounds that mimic the effects of Ser23/24 phospho-TnI may be an effective strategy in correcting diastolic dysfunction in HF-pEF.
CXC-Chemokines/CXCR2 mediate a novel pathway of angiogenesis in pancreatic cancer
Authors: Sushovan Guha, Robert Bresalier, Robert Hoffman, Marie Burdick, Robert Strieter
Journal: Cancer Research (2007)

4616  Background: ELR+-CXC-chemokines promote angiogenesis in multiple cancers including NSCLC and renal cell carcinoma. These chemokines including IL-8/CXCL8, ENA-78/CXCL5, GRO-γ/CXCL3 bind to their cognate receptors including CXCR2, member of G protein-coupled receptor (GPCR) superfamily. CXCR2 promotes ELR+-CXC-chemokine mediated angiogenesis in multiple cancers. Little is known about the expression and regulation of ELR+-CXC-chemokines/CXCR2 in pancreatic cancer (PaCa) and human microvascular endothelial cells (HMEC). Also, the role of ELR+-CXC-chemokines/CXCR2 biological axis in promoting PaCa angiogenesis in vivo is unknown.  Aim: To examine the expression and regulation of ELR+-CXC-chemokines in PaCa and HMEC. To determine the effects of CXCR2 blockade with a specific antibody on PaCa growth and angiogenesis in vivo.  Methods and Results: ELR+-CXC-chemokines including IL-8/CXCL8, ENA-78/CXCL5, GRO-γ/CXCL3 are produced by PaCa cells including BxPC-3 (highest), AsPC-1, Capan-2, MIA PaCa-2, and PANC-1 (lowest). Neurotensin (NT), GPCR agonist, potently increased protein kinase C (PKC)-mediated NF-κB-dependent IL-8/CXCL8 secretion in PANC-1. CXCR2 is present on HMEC but not on PaCa cells (by RT-PCR and western blots). Hypoxic preconditioning of HMEC significantly increased chemotaxis in response to IL-8/CXCL8 in a CXCR2-depepdent manner. Next, CXCR2 specific polyclonal antibody potently blocked PaCa cell-induced angiogenesis in rat corneal nicropocket angiogenesis assay. Using a BxPC-3-GFP orthotopic PaCa model in nude mice, we detected 64% decrease in tumor volume in the CXCR2 antibody-treated group (p  Conclusions: GPCRs regulate expression of ELR+-CXC-chemokines in PaCa and hypoxia regulates expression of CXCR2 on HMEC. Thus, ELR+-CXC-chemokines/CXCR2 biological axis is functional in PaCa. CXCR2 blockade with specific antibody potently reduced PaCa tumor growth and angiogenesis in vivo. Our results, for the first time, demonstrate that CXCR2 inhibitors are potent anti-angiogenic agents against PaCa in addition to VEGF antagonists.
Clinical evolution of patients with chronic spontaneous urticaria steroid-dependent
Authors: Raisa Borges Castro, Rafaella amorim gaia Duarte, Andressa Zanandréa, Claudia Castilho Mouco, Joao Paulo de Assis, Gabriella Melo Fontes Silva Dias, Franciane Almonfrey, Rebeca M. Brugnolli, Jorge Kalil, Rosana C. Agondi
Journal: Journal of Allergy and Clinical Immunology (2018)
Generic Respiratory Symptoms and Branded Lung Diseases. Same Difference?
Authors: Surya P. Bhatt
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

associated with HIV infection.In work from our lab, we have seen a significant increase in the total virome burden in the lungs of asymptomatic HIV-infected individuals compared with healthy control subjects, with various herpes virus species being a major driver of this difference (unpublished results, H. Twigg III and colleagues), and we are in the process of linking the lung virome to local inflammation and evidence of lung disease.Not all of the news is bad.In the article by Collini and colleagues, there is a strong positive association between the BAL CD4:CD8 ratio and the ability of alveolar macrophages to undergo apoptosis after pneumococcus exposure.This suggests that pulmonary immune reconstitution can return alveolar macrophage function toward normal.Furthermore, individuals with the greatest concentrations of gp120 in BAL had the lowest peripheral blood CD4 counts.In this regard, it is notable that the mean nadir peripheral blood CD4 count in the subjects on ART was 216 cells/mm 3 .This in fact is a potential limitation of the study by Collini and colleagues, as CD4 levels this low are not commonly encountered these days, when early treatment with ART is the standard for HIV-infected subjects (13).Thus, the subjects in the study by Collini and colleagues demonstrated a more profound immune defect at the time of HIV diagnosis, which is known to impact an individual's ability to recover normal immune function even in the presence of good viral control ( 14).The longer we live, the more likely we are to acquire viruses, many of which are capable of establishing a latent or persistent infection.Any immunodeficiency can accelerate this process.Most clinicians are already cognizant that many viruses, once acquired, are almost impossible to eradicate, including herpes viruses and papilloma viruses.For now, until the NIH HIV Cure initiative reaches it goals, so is HIV.The inability to detect viruses in blood or tissues at any one time is not synonymous with cure.Successful approaches to curing viral infections will involve not only controlling active replication but also eradicating viral stores, wherever they may lie.Only in this way can we finally get rid of potentially pathologic viruses and their proteins, and hopefully along the way abrogate the chronic inflammation that leads to disease in both HIV-infected and aging populations.
Les suppositoires d'AINS sont surs et probablement efficaces dans la prévention de la pancréatite post-CPRE chez les patients de 80 ans et plus: étude comparative appariée
Authors: C Genin, L Rinaldi, R Kassir, M Fovet, O Dumas, X Roblin, JM Phelip, N Williet
Journal: Endoscopy (2018)

Malgré les recommandations de l'ESGE (European Society of Gastrointestinal Endoscopy) concernant la pratique de la cholangiopancréatografie endoscopique rétrograde (CPRE), seuls 20% des gastroentérologues en 2012 administraient systématiquement un suppositoire d'AINS en prévention de la pancréatite aiguë post-CPRE (PAP), notamment par crainte des effets secondaires potentiels. A l'inverse, l'utilisation des AINS doit être prudente chez les personnes âgées. L'objectif de notre étude était d'évaluer l'efficacité et la toxicité potentielle de l'utilisation d'un suppositoire d'AINS dans cette indication.
Diabetes Mellitus and Cardiomyopathy:Association With Mutation in the Mitochondrial tRNA Leu(UUR) gene
Authors: Hideyuki Shiotani, Hiroshi Ueno, Satoko Inoue, Yoshiyuki Yokota, Mitsuhiro Yokoyama
Journal: Circulation (1998)

In this report, cardiac abnormalities in 2 diabetic patients with a mutation in the mitochondrial tRNA(Leu)(UUR)gene are described. The 2 patients exhibited left ventricular dilation and diffuse decreased wall motion. Cardiac catheterization studies revealed normal coronary angiography. In both patients, light microscopic examination of hematoxylin and eosin-stained sections revealed myocyte hypertrophy and perinuclear vacuolization and electron microscopy revealed an increase in the number and size of mitochondria and abnormal configuration of cristae. These findings suggest that mutations in mitochondrial DNA, such as an A-->G mutation at position 3243, should be considered as a cause not only of diabetes mellitus but also of cardiac involvement in patients with diabetes mellitus.
L'endomicroscopie confocale par mini-sonde pour évaluer la rémission histologique dans la rectocolite hémorragique: Résultats d'une étude prospective multicentrique sur 100 patients
Authors: G Rahmi, E Coron, M Lévy, J Moreau, D Moussata, G Perrod, A Bourreille, C Trang Poisson, L Quénéhervé, E Samaha, A Bressenot-Marchal, L Peyrin-Biroulet, C Cellier
Journal: Endoscopy (2018)

La rémission histologique est un nouvel objectif thérapeutique chez les patients atteints d'une rectocolite hémorragique (RCH). L'endomicroscopie confocale par minisonde (ECM) permet un examen in vivo à l'échelle microscopique de la muqueuse colique. L'objectif de cette étude est d'évaluer l'efficacité de l'ECM pour déterminer la présence d'une inflammation colique au niveau microscopique chez des patients en rémission clinique et endoscopique.
Safety and Efficacy of Pomalidomide (POM) + Low-Dose Dexamethasone (LoDEX) + Daratumumab (DARA) As Second- or Third-Line Therapy in Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM) after Lenalidomide (LEN)-Based Treatment (Tx) Failure
Authors: David Siegel, Gary J. Schiller, Christy Samaras, Michael Sebag, Jesus G. Berdeja, Siddhartha Ganguly, Jeffrey V. Matous, Kevin W Song, Christopher S. Seet, Giampaolo Talamo, Shanthi Srinivas, Mirelis Acosta-Rivera, Michael Bar, Donald Quick, Bertrand Anz, Gustavo Fonseca, Donna Reece, Jorge Mouro, Amit Agarwal, Faiza Zafar, Max Qian, Anjan Thakurta, Nizar J. Bahlis
Journal: Blood (2017)
Origins of lifetime health around the time of conception: causes and consequences
Authors: Tom P Fleming, Adam J Watkins, Miguel A Velazquez, John C Mathers, Andrew M Prentice, Judith Stephenson, Mary Barker, Richard Saffery, Chittaranjan S Yajnik, Judith J Eckert, Mark A Hanson, Terrence Forrester, Peter D Gluckman, Keith M Godfrey
Journal: The Lancet (2018)
La sévérité des lésions endoscopiques dans la recto-colite hémorragique: entre l'appréciation de l'endoscopiste et le «Ulcerative Colitis Endoscopic Index Score (UCEIS)»
Authors: A Sabbek, N Elleuch, A Ben Slama, H Jaziri, A Hammami, A Braham, S Ajmi, M Ksiaa, A Jmaa
Journal: Endoscopy (2018)

Il existe une grande variabilité dans la description des lésions et dans l'appréciation de leur gravité endoscopique au cours des poussées de la rectocolite hémorragique (RCH). L'UCEIS (Ulcerative Colitis Endoscopic Index of Severity) a récemment été validé pour homogénéiser la description des lésions de façon reproductible permettant ainsi la standardisation des comptes rendus endoscopiques et par conséquent de codifier la prise en charge.
Sixty seconds on . . . Heineken
Authors: Anne Gulland
Journal: BMJ (2018)

The very same. It’s in the news because it is to provide logistics experts to the Global Fund to Fight Aids, Tuberculosis, and Malaria to help it deliver health supplies and medicines to remote communities in Africa.

Absolutely. The partnership is starting in the Democratic Republic of Congo (DRC), Nigeria, and South Africa—countries where, according to the fund, …
FLABRA, frontline approach for BRCA testing in ovarian cancer (OC) treatment naïve population: A Latin America (LA) epidemiologic study.
Authors: Susana Beatriz Goncalves, Gonzalo Giornelli, Marcelo Horacio Pereira, Dolores Gallardo-Rincon, Maria Del Pilar Estevez-Diz
Journal: Journal of Clinical Oncology (2019)

e17050 Background: The majority of OC cases are sporadic, but it is estimated that in 17%, germline mutations in BRCA1 or BRCA2 genes can be identified. BRCA mutated OC has distinct clinical characteristics, increased sensitivity to platinum and non-platinum agents, and to DNA damage repair (DDR) targeting agents like PARP inhibitors. Additionally, somatic BRCA mutations could be identified in tumor tissue. The prevalence of germline BRCA mutations (gBRCAm) and somatic mutations (sBRCAm) has been not been characterized in Latin-american population, which is a paradigm of poly-ethnicity, where prevalence of germline, but especially somatic BRCA mutations in OC, has not been studied. Furthermore, tumor testing as first step may be a new option in BRCA testing algorithm that could avoid the necessity for double testing (gBRCA, then sBRCA testing), in case of gBRCAm negative result. Methods: FLABRA is a cross-sectional, multi-center, study designed to determine the prevalence of sBRCAm in newly diagnosed OC patients versus gBRCAm, and to describe different treatment approaches at front line in LA, as well as current OC genetic counselling. We enrolled 400 consecutive patients from 40 institutions in Argentina, Brazil, Colombia, Mexico, Peru and Panama, diagnosed with OC. Tumor blocks were tested for sBRCA (Myriad Tumor BRACAnalysis CDx™). In sBRCA positive patients, blood samples were analyzed to confirm if the mutation was germline or somatic in origin. In gBRCAm, genetic counseling was advised. Medical records were reviewed for data relevant to medical history, surgery results, treatment approach and genetic counseling. Results: We present the preliminary results with 291 patients already tested. For this first subset of patients, 85/291 (29%) had BRCA mutations identified in their tumors. Preliminary results confirm that starting with tumor testing enlarges the population eligible for PARP inhibitors, by identifying additional patients with somatic mutations only detectable in the tumor. Although preliminary, our data confirms the possibility of identifying additional patients with sBRCA mutations by testing in tumor, with a more cost-effective approach, avoiding a second round of gBRCA testing in patients with BRCA negative results in tumor. Conclusions: In this preliminary analysis we found that somatic BRCA mutations account for a significant proportion from total BRCA mutations within LA population studied.
Impact of asthma control on susceptibility to ambient air pollution among African American teens with asthma
Authors: Michelle L. Hernandez, Radhika Dhingra, Allison J. Burbank, Krista Todoric, Ceila Loughlin, Marcia Frye, Kelly E. Duncan, Carole Robinette, Katherine H. Mills, Robert Devlin, David B. Peden, David Diaz Sanchez
Journal: Journal of Allergy and Clinical Immunology (2018)
Drug shortages derail CCGs’ budgets
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Financial plans of clinical commissioning groups are being derailed by emergency hikes in prices of generic drugs, which have led to soaring costs, The BMJ has learnt.

Last month The BMJ reported that ongoing shortages of generic drugs cost the NHS £38m in November 2017,1 as the government agreed more emergency price increases to boost stocks.

An examination of board papers by The BMJ has found that many CCGs are reporting significant risks to their financial plans as a result of the price increases. Included are some of the most financially stricken CCGs that were ordered by NHS England and NHS Improvement to draw up radical cost savings plans this year as …
Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II–IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised phase 3 trial
Authors: Lin-Quan Tang, Dong-Ping Chen, Ling Guo, Hao-Yuan Mo, Ying Huang, Shan-Shan Guo, Bin Qi, Qing-Nan Tang, Pan Wang, Xiao-Yun Li, Ji-Bin Li, Qing Liu, Yuan-Hong Gao, Fang-Yun Xie, Li-Ting Liu, Yang Li, Sai-Lan Liu, Hao-Jun Xie, Yu-Jing Liang, Xue-Song Sun, Jin-Jie Yan, Yi-Shan Wu, Dong-Hua Luo, Pei-Yu Huang, Yan-Qun Xiang, Rui Sun, Ming-Yuan Chen, Xing Lv, Lin Wang, Wei-Xiong Xia, Chong Zhao, Ka-Jia Cao, Chao-Nan Qian, Xiang Guo, Ming-Huang Hong, Zhi-Qiang Nie, Qiu-Yan Chen, Hai-Qiang Mai
Journal: The Lancet Oncology (2018)
Fistules persistantes après retrait de gastrostomie: prévalence, facteurs associés et prise en charge endoscopique par clip OVESCO: A propos d'une série de 16 patients au centre hospitalier STE Musse Toulon
Authors: R Zeriguine, P Mercky, AD Le Goffic, F Chinoune, P Ah-Soune, P Grandval
Journal: Endoscopy (2018)

Les fistules persistantes après retrait de gastrostomie représentent une complication relativement rare. Leur prévalence dans la population adulte est mal évaluée. Les facteurs de risques de non fermeture de fistule après gastrostomie ne sont pas clairement établis. Le principal facteur de risque de non fermeture reconnu dans la littérature était le temps de pose de la sonde de gastrostomie. De nouvelles techniques endoscopiques de fermeture des fistules sont possibles permettant de réduire le recours à la chirurgie.