tbuckley/cabot-search huggingface dataset:
miR-206 Mediates YAP-Induced Cardiac Hypertrophy and Survival
Authors: Yanfei Yang, Dominic P. Del Re, Noritsugu Nakano, Sebastiano Sciarretta, Peiyong Zhai, Jiyeon Park, Danish Sayed, Akihiro Shirakabe, Shoji Matsushima, Yongkyu Park, Bin Tian, Maha Abdellatif, Junichi Sadoshima
Journal: Circulation Research (2015)

Rationale: In Drosophila , the Hippo signaling pathway negatively regulates organ size by suppressing cell proliferation and survival through the inhibition of Yorkie, a transcriptional cofactor. Yes-associated protein (YAP), the mammalian homolog of Yorkie, promotes cardiomyocyte growth and survival in postnatal hearts. However, the underlying mechanism responsible for the beneficial effect of YAP in cardiomyocytes remains unclear. Objectives: We investigated whether miR-206, a microRNA known to promote hypertrophy in skeletal muscle, mediates the effect of YAP on promotion of survival and hypertrophy in cardiomyocytes. Methods and Results: Microarray analysis indicated that YAP increased miR-206 expression in cardiomyocytes. Increased miR-206 expression induced cardiac hypertrophy and inhibited cell death in cultured cardiomyocytes, similar to that of YAP. Downregulation of endogenous miR-206 in cardiomyocytes attenuated YAP-induced cardiac hypertrophy and survival, suggesting that miR-206 plays a critical role in mediating YAP function. Cardiac-specific overexpression of miR-206 in mice induced hypertrophy and protected the heart from ischemia/reperfusion injury, whereas suppression of miR-206 exacerbated ischemia/reperfusion injury and prevented pressure overload-induced cardiac hypertrophy. miR-206 negatively regulates Forkhead box protein P1 expression in cardiomyocytes and overexpression of Forkhead box protein P1 attenuated miR-206–induced cardiac hypertrophy and survival, suggesting that Forkhead box protein P1 is a functional target of miR-206. Conclusions: YAP increases the abundance of miR-206, which in turn plays an essential role in mediating hypertrophy and survival by silencing Forkhead box protein P1 in cardiomyocytes.
Scheduling Nab-Paclitaxel with Gemcitabine (Siege): Randomised Phase Ii Trial to Investigate Two Different Schedules of Nab-Paclitaxel (Abx) Combined with Gemcitabine (Gem) As First Line Treatment for Metastatic Pancreatic Adenocarcinoma (Pdac)
Authors: P. Corrie, W. Qian, D.I. Jodrell, S. Lao-Sirieix, P. Whittaker, A. Gopinathan, A. Chhabra, K. Dalchau, B. Basu, R. Hardy, J.W. Valle
Journal: Annals of Oncology (2014)
Systemic Therapy for Metastatic Melanoma in 2012: Dawn of a New Era
Authors: Shailender Bhatia, John A. Thompson
Journal: Journal of the National Comprehensive Cancer Network (2012)

The 10-year survival rate for patients with metastatic melanoma is less than 10%. Although surgery and radiation therapy have a role in the treatment of metastatic disease, systemic therapy is the mainstay of treatment for these patients. After decades of failed attempts to improve treatment outcomes, recent successes with ipilimumab and vemurafenib have ushered in a new era in systemic therapy. Both ipilimumab and vemurafenib are associated with significant improvements in overall survival of patients in randomized phase III trials, an end point that had proven elusive so far. These breakthroughs not only provide more treatment options for patients with melanoma but also spur the investigation of a new generation of drugs for cancer therapy in general. This article reviews both the current systemic treatment options for metastatic melanoma and promising investigational approaches.
Long-term use of inhaled corticoids on the development of pleural effusion in community-acquired pneumonia
Authors: Alejandra Lopez-Giraldo, Jacobo Sellarés, Carmen Lucena, Eva Polverino, Catia Cilloniz, Rosanel Amaro, Maria Angeles Marcos, Josep Mensa, Antoni Torres
Journal: European Respiratory Journal (2012)

Introduction

Long-term use of inhaled corticosteroids (ICS) in patients with Chronic Obstructive Pulmonary Disease (COPD) has been associated with increase risk of CAP. Most recently, ICS have been associated with less severity of CAP and decreased risk of pneumonia-related mortality. Pleural infection is a frequent complication of CAP that may increase mortality. The aim of this study was to assess the influence of long-term use of ICS on the incidence and severity of parapneumonic effusion and empyiema in patients with different baseline respiratory diseases.

Methods

We conducted a single centre cohort study of 3602 patients consecutively collected with CAP. We assessed clinical, radiographic and pleural fluid chemistry and microbiological variables. Patients were classified whether they received prior long term ICS treatment or not.

Results

659 patients (18%) were treated with ICS before diagnosis of CAP (COPD: 56%). Long-term use of ICS was significant associated with less incidence of parapneumonic effusion compared to those without prior ICS treatment 5% vs. 12%, p<0.001. Multivariate analysis adjusted by sex, age, comorbidities and CAP severity showed a significant association between ICS treatment and lower incidence of pleural effusion (OR 0.42 (95% CI, 0.28-0.64, p<0.001). Prior treatment with ICS was significantly associated with lower incidence of empyiema compared to those without ICS treatment (3% vs 16%, p=0.05).

Conclusions

Long-term use of ICS in patients who develop CAP is associated with lower incidence and less severity of parapneumonic effusion regardless of the baseline chronic respiratory condition.

Supported by: CibeRes-ISCiii-CB06/06/0028 and IDIBAPS.
Multiple tumor associated peptide vaccination as consolidation treatment in women affected by breast and ovarian cancer.
Authors: M. Nuti, F. Bellati, C. Napoletano, V. Visconti, M. Antonilli, H. Rahimi, S. Pauselli, A. Rughetti, L. Frati, P. Benedetti Panici
Journal: Journal of Clinical Oncology (2010)

TPS172 Background: Breast and ovarian cancer remain two of the most lethal malignancies in developed countries (Jemal A. CA Cancer J Clin. 2009;59:225). In breast cancer (Paik S. N Engl J Med. 2008;358:1409; Arimidex, Forbes JF. Lancet Oncol. 2008;9:45), current consolidation treatments includes monoclonal antibodies and hormone therapy. In ovarian cancer, several trials have attempted to introduce consolidation chemotherapy regimens, but up to now no treatment has been show to improve survival (Pecorelli S. J Clin Oncol. 2009;27:4642). Several attempts to introduce immunotherapy in cancer treatments have been carried out mostly without yielding significant clinical results. All these studies were carried out in palliative settings and on patients with high tumor burden. Recent studies have demonstrated opposing results of vaccination protocols in patient with minimal residual disease (Peoples GE. J Clin Oncol. 2005;23:7536; MAGA-A Clinical Trial ASCI). In addition, in vivo studies have unrevealed new immunological mechanisms, such as epitope spread, and new adjuvants that can significantly increase the efficacy of the novel immunotherapic strategies. The objective of the present study is to evaluate the feasibility and safety and immunological response to a multiple peptide (Erb-B2, MUC-1, CEA) vaccination carried out with Montanide ISA-51 and GM-CSF in high risk patients who have completed treatment and are in clinical disease remission. Methods: Phase I/II trial will enrol HLA- A2 aplotype with no evidence of disease high risk breast and ovarian cancer patients. Currently 14 patients have been accrued and have completed treatment. The vaccination protocol consists of six consecutive peptide vaccine administration and a recall dose at 3 months from the sixth vaccination. Follow-up will be carried out for 24 months to register local and systemic side effects and to evaluate the immunological changes with time. Immunological analyses include specific circulating CD8+ and functional response including T-cell cytotoxicity assessed by Elispot (Granzymes). Serum immunosuppressive and immune activating cytokines will be quantitatively evaluated by ELISA. No significant financial relationships to disclose.
Management and follow up of non-tuberculosis mycobacteria pulmonary infection in 55 infected cases in Iran
Authors: Parvaneh Baghaei Shiva, Payam Tabarsi, Majid Marjani, Mohammad Reza Masjedi
Journal: European Respiratory Journal (2011)

Background:  Non-Tuberculosis Mycobacteria (NTM) are increasing worldwide. This study defines type and outcome of treatment in a referral center in Tehran   Methods:  Study was done in national referral center in Tehran during 2002-2009. All patients with documented NTM pulmonary diseases (based on ATS criteria) were included in study. Patient9s data and treatment outcomes were extracted from medical records.   Results:  55 patients with NTM pulmonary disease were diagnosed. Female were predominant (52.7%).Mean age was 54.43±15.61.History of smoking was present in 17 (30.9%) and 9 (16.4%) were opium addicted. only one patient was HIV positive.  The most common type was Mycobacterium simiae in 26 (47.3%) followed by M.Chelonae in 8 (14.5%), M.Kansasii in 8 (14.5%), M. Abscessus in 6 (10.9%), M.Avium in 5 (9.1%) and M.Farcinogen and M.Genavense each in one case.  Cavitary lung lesion was seen in 72.8% and bronchiectasis in 80% of patients.  The most predominant symptoms were cough (89.1%), sputum (85, 5%) and dyspnea (65.5%).Fever was present in 22 (40%) of patients.  Cure occurred in 38 (69.1%) of patients. Sixteen patients failed treatment and only one patient died.   Conclusion:  In comparison with other studies M.Simiae was more prevalent and HIV seropositivity was rare.
Bacterial infection in compensated viral cirrhosis impairs 5-year survival (ANRS CO12 CirVir prospective cohort)
Authors: Pierre Nahon, Mathilde Lescat, Richard Layese, Valérie Bourcier, Nabila Talmat, Setty Allam, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Jean-Pierre Zarski, Odile Goria, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Jean-Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle, Thông Dao, Yves Benhamou, Christophe Pilette, Christine Silvain, Christos Christidis, Dominique Capron, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Jean-Claude Trinchet, Richard Moreau, Françoise Roudot-Thoraval
Journal: Gut (2015)

<h3>Objective</h3> To assess incidence and prognostic significance of bacterial infections (BIs) occurring in compensated viral cirrhosis. <h3>Design</h3> This prospective study involved 35 French centres. Inclusion criteria were biopsy-proven HCV or HBV cirrhosis, Child–Pugh A and no previous hepatic complications. Cumulative incidence (CumI) of events was estimated in a competing risks framework. <h3>Results</h3> 1672 patients were enrolled (HCV 1323, HBV 318, HCV-HBV 31). During a median follow-up of 43 months, 234 BIs occurred in 171 patients (5 year CumI: 12.9%), among whom 14.6% had septic shock. Main localisations included the urinary tract (27.4%), lung (25.2%) and peritoneum (10.7%) (other, 86 (36.7%)). Most BIs occurred as a first event prior to liver decompensation (n=140, 81.8%) and were community-acquired (CA, 84.2%). The risk of BI was higher in patients with HCV than in patients with HBV (5 year CumI: 15.2% vs 5.5%, p=0.0008). Digestive localisation, concomitant interferon-based treatment, isolation of resistant bacteria and non-CA BIs were associated with lowest probability of resolution. The occurrence of a first BI impaired survival in patients infected with HCV (5 year survival: 60.2% vs 90.4%, p&lt;0.001) and patients infected with HBV (5 year survival: 69.2% vs 97.6%, p&lt;0.001). BIs represented the third cause of death (14.1%) after liver failure and liver cancer. BI risk factors comprised older age, lower albumin, proton pump inhibitor intake and absence of virological eradication/control. <h3>Conclusion</h3> BI mostly occurs as a first complication and represents a turning point in the course of compensated viral cirrhosis. Its occurrence impacts long-term prognosis and may define a subgroup of patients in whom adaptation of management is warranted.
White House boosts public health role in response to heroin epidemic
Authors: Michael McCarthy
Journal: BMJ (2015)

In the face of a growing epidemic of heroin misuse in the United States, the White House announced on 17 August a $13.4m (£8.6m; €12m) initiative to promote law enforcement and public health programs in areas where misuse of heroin and prescription opioids has surged.

The funds will be parceled out to programs in areas that have been determined to be critical drug trafficking regions, designated “high intensity drug trafficking areas” (HIDTAs). There are currently 28 such areas in the 48 states, Puerto Rico, the US Virgin Islands, and …
The impact of obstructive sleep apnea on abdominal aortic diameters
Authors: Ryo Tachikawa, Satoshi Hamada, Masanori Azuma, Yoshiro Toyama, Kimihiko Murase, Kiminobu Tanizawa, Morito Inouchi, Tomohiro Handa, Toru Oga, Michiaki Mishima, Kazuo Chin
Journal: European Respiratory Journal (2014)

Background/Objectives: Although obesity has been reported to be a potential risk factor for abdominal aortic dilatation and abdominal aortic aneurysm, the impact of obstructive sleep apnea (OSA) on abdominal aortic diameter remains to be elucidated.This study aimed to investigate the impact of OSA on abdominal aortic diameters.

Methods: We retrospectively reviewed consecutive 430 patients over 45 years old who underwent polysomnography and an abdominal CT scan from November 2008 to February 2012. Aortic diameters were measured at three locations: just inferior to the supramesenteric artery (upper abdominal aorta [UAA]); maximum diameter below the renal arteries (infrarenal aorta [IRA]); just superior to the aortoiliac bifurcation (lower abdominal aorta [LAA]).

Results: OSA was defined as non-OSA (AHI <10, n=58), mild/moderate (AHI 10-30, n=169), and severe (AHI ≥30, n=203). Adjusted aortic diameter was not significantly different among OSA severity categories at the UAA (21.0, 21.4, and 21.5 mm, respectively) and IRA (19.5, 20.2, and 19.9 mm, respectively), but was significantly different at the LAA (17.3, 18.3, and 18.2 mm, respectively, P=0.005) with larger diameters in patients with OSA. Multivariate linear regression analyses revealed that risk profiles for aortic dilatation varied according to the aortic locations and sex, and OSA (AHI ≥10) was an independent risk factor for IRA and LAA dilatation in men in addition to traditional risk factors including age, body surface area, and smoking.

Conclusions: OSA may enhance degenerative dilatation of the distal abdominal aorta, which is known to be a risk factor for developing of an abdominal aortic aneurysm.
Trastuzumab-Related Cardiac Dysfunction
Authors: Melinda L. Telli, Ronald M. Witteles
Journal: Journal of the National Comprehensive Cancer Network (2011)

The use of trastuzumab in the adjuvant and metastatic treatment of breast cancer is associated with both symptomatic and asymptomatic cardiotoxicity. The long-term significance of these events, isolating known cardiotoxic effects of anthracyclines from those of trastuzumab, and the appropriateness of referring to trastuzumab-related cardiotoxicity as reversible rather than responsive to trastuzumab withdrawal and heart failure medical therapy, are issues that continue to be debated. This article provides an overview of the available cardiac safety data from the major trastuzumab clinical trials in breast cancer, highlighting areas of ongoing controversy. Important recent data documenting the occurrence and prognostic use of cardiac troponin I elevations among patients treated with trastuzumab are placed into context with the mechanistic insight these data provide and the implications for clinical practice today.
Analysis of EF-hand-containing proteins in Arabidopsis
Authors: Irene S Day, Vaka S Reddy, Gul Shad Ali, ASN Reddy
Journal: Genome biology (2002)

In plants, calcium (Ca2+) has emerged as an important messenger mediating the action of many hormonal and environmental signals, including biotic and abiotic stresses. Many different signals raise cytosolic calcium concentration ([Ca2+]cyt), which in turn is thought to regulate cellular and developmental processes via Ca2+-binding proteins. Three out of the four classes of Ca2+-binding proteins in plants contain Ca2+-binding EF-hand motif(s). This motif is a conserved helix-loop-helix structure that can bind a single Ca2+ ion. To identify all EF-hand-containing proteins in Arabidopsis, we analyzed its completed genome sequence for genes encoding EF-hand-containing proteins.A maximum of 250 proteins possibly having EF-hands were identified. Diverse proteins, including enzymes, proteins involved in transcription and translation, protein- and nucleic-acid-binding proteins and a large number of unknown proteins, have one or more putative EF-hands. Phylogenetic analysis identified six major groups that contain some families of proteins.The presence of EF-hand motif(s) in a diversity of proteins is consistent with the involvement of Ca2+ in regulating many cellular and developmental processes. Thus far, only 47 of the possible 250 EF-hand proteins have been reported in the literature. Various domains that we identified in many of the uncharacterized EF-hand-containing proteins should help in elucidating their cellular role(s). Our analyses suggest that the Ca2+ messenger system is widely used in plants and that EF-hand-containing proteins are likely to be the key transducers mediating Ca2+ action.
Catecholamine Metabolism in Neuroblastoma 1 2
Authors: Elwood H. LaBrosse, Etienne Comoy, Claude Bohuon, Jean-Michel Zucker, Odile Schweisguth
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Catecholamine Metabolism in Neuroblastoma Get access Elwood H. LaBrosse, Elwood H. LaBrosse Search for other works by this author on: Oxford Academic PubMed Google Scholar Etienne Comoy, Etienne Comoy Search for other works by this author on: Oxford Academic PubMed Google Scholar Claude Bohuon, Claude Bohuon Search for other works by this author on: Oxford Academic PubMed Google Scholar Jean-Michel Zucker, Jean-Michel Zucker Search for other works by this author on: Oxford Academic PubMed Google Scholar Odile Schweisguth Odile Schweisguth Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 3, September 1976, Pages 633–643, https://doi.org/10.1093/jnci/57.3.633 Published: 01 September 1976
Intracellular signalling during neutrophil recruitment
Authors: Attila Mócsai, Barbara Walzog, Clifford A. Lowell
Journal: Cardiovascular Research (2015)

Recruitment of leucocytes such as neutrophils to the extravascular space is a critical step of the inflammation process and plays a major role in the development of various diseases including several cardiovascular diseases. Neutrophils themselves play a very active role in that process by sensing their environment and responding to the extracellular cues by adhesion and de-adhesion, cellular shape changes, chemotactic migration, and other effector functions of cell activation. Those responses are co-ordinated by a number of cell surface receptors and their complex intracellular signal transduction pathways. Here, we review neutrophil signal transduction processes critical for recruitment to the site of inflammation. The two key requirements for neutrophil recruitment are the establishment of appropriate chemoattractant gradients and the intrinsic ability of the cells to migrate along those gradients. We will first discuss signalling steps required for sensing extracellular chemoattractants such as chemokines and lipid mediators and the processes (e.g. PI3-kinase pathways) leading to the translation of extracellular chemoattractant gradients to polarized cellular responses. We will then discuss signal transduction by leucocyte adhesion receptors (e.g. tyrosine kinase pathways) which are critical for adhesion to, and migration through the vessel wall. Finally, additional neutrophil signalling pathways with an indirect effect on the neutrophil recruitment process, e.g. through modulation of the inflammatory environment, will be discussed. Mechanistic understanding of these pathways provide better understanding of the inflammation process and may point to novel therapeutic strategies for controlling excessive inflammation during infection or tissue damage.
Synergistic Growth Inhibitory Activity of Combined Mek/Mtor Pathway Blockade in Pten-Null Cancers
Authors: L. Ciuffreda, I. Falcone, A. Benfante, S. Matteoni, A. Eramo, G. Sette, T. De Luca, A. Sacconi, F. Malusa, U. Cesta Incani, A. Del Curatolo, M. Konopleva, M. Andreeff, D. Del Bufalo, F. Cognetti, R. De Maria, M. Todaro, G. Stassi, M. Milella
Journal: Annals of Oncology (2014)
Lifespan and Incidence of Cancer and Other Diseases in Selected Long-Lived Inbred Mice and Their F1 Hybrids2
Authors: G S Smith, R L Walford, M R Mickey
Journal: JNCI Journal of the National Cancer Institute (1973)

Survival patterns and tumor incidence are presented for long-lived mouse strains LP, 129, DBA/2, CBA, C57BL/10, C3H, and C3H.K and 8 derived F1 hybrid groups. In almost all strains, males lived longer than females. Overall, the F1 hybrid combinations of noncongenic parents had not only an increased tumor incidence but also an increased lifespan. The lifespan and age-specific incidence of cancer observed for the F1 hybrids could not be accurately predicted from the parental characteristics.
An Introduction to Acarology
Authors: Edward William Baker, George Willard Wharton
Journal: JAMA (1952)

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