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Pulmonary hypertension and cancer

Yufeng Du, Xiaoyan Hao, Xuejun Liu
The present study aimed to investigate the expression of long non-coding RNA (lncRNA) cyclin dependent kinase inhibitor-2B-antisense RNA 1 CDKN2B-AS1 in patients with peripheral blood of idiopathic pulmonary fibrosis (IPF). A total of 24 patients with IPF and 24 healthy controls were included in the study, four patients with IPF and four healthy controls were selected randomly to extract RNA. There were no other diseases such as hypertension and diabetes in the two groups. RNA from peripheral blood was extracted by high-throughput sequencing and bioinformatics analysis was performed...
April 2018: Oncology Letters
Thenappan Thenappan, Mark L Ormiston, John J Ryan, Stephen L Archer
Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 mm Hg or above. This review deals with pulmonary arterial hypertension (PAH), a type of pulmonary hypertension that primarily affects the pulmonary vasculature. In PAH, the pulmonary vasculature is dynamically obstructed by vasoconstriction, structurally obstructed by adverse vascular remodeling, and pathologically non-compliant as a result of vascular fibrosis and stiffening. Many cell types are abnormal in PAH, including vascular cells (endothelial cells, smooth muscle cells, and fibroblasts) and inflammatory cells...
March 14, 2018: BMJ: British Medical Journal
Morane Le Hiress, Bernardin Akagah, Guillaume Bernadat, Ly Tu, Raphaël Thuillet, Alice Huertas, Carole Phan, Elie Fadel, Gérald Simonneau, Marc Humbert, Gaël Jalce, Christophe Guignabert
Macrophage migration inhibitory factor (MIF) is a key pleiotropic mediator and a promising therapeutic target in cancer as well as in several inflammatory and cardiovascular diseases including pulmonary arterial hypertension (PAH). Here, a novel series of N-(phenylmethyl)-benzoxazol-2-thiones 5-32 designed to target the MIF tautomerase active site was synthesized and evaluated for its effects on cell survival. Investigation of structure-activity relationship (SAR) particularly at the 5-position of the benzoxazole core led to the identification of 31 that potently inhibits cell survival in DU-145 prostate cancer cells and pulmonary endothelial cells derived from patients with idiopathic PAH (iPAH-ECs), two cell lines for which survival is MIF-dependent...
March 10, 2018: Journal of Medicinal Chemistry
Oliver T Mytton, Christopher Jackson, Arno Steinacher, Anna Goodman, Claudia Langenberg, Simon Griffin, Nick Wareham, James Woodcock
BACKGROUND: The National Health Service (NHS) Health Check programme was introduced in 2009 in England to systematically assess all adults in midlife for cardiovascular disease risk factors. However, its current benefit and impact on health inequalities are unknown. It is also unclear whether feasible changes in how it is delivered could result in increased benefits. It is one of the first such programmes in the world. We sought to estimate the health benefits and effect on inequalities of the current NHS Health Check programme and the impact of making feasible changes to its implementation...
March 2018: PLoS Medicine
Tatsuyuki Sato, Masaya Mori, Jiro Aoki, Kengo Tanabe
Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related complication characterized by severe progressive pulmonary hypertension. Antemortem diagnosis is difficult owing to the rapid progression of the condition, especially when the patient has no known malignancies and initially presents with pulmonary hypertension. Here we report a case of PTTM due to occult gastric cancer with metastasis in the left supraclavicular lymph node, also known as Virchow's node. Enlarged Virchow's node is an important indicator of advanced gastric cancer...
March 5, 2018: International Heart Journal
Jens M Hohlfeld, Jens Vogel-Claussen, Heike Biller, Dominik Berliner, Korbinian Berschneider, Hanns-Christian Tillmann, Simone Hiltl, Johann Bauersachs, Tobias Welte
BACKGROUND: Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with reduced biventricular end-diastolic volumes and increased morbidity and mortality. The combination of a long-acting β agonist (LABA) and a muscarinic antagonist (LAMA) is more effective in reducing hyperinflation than LABA-inhaled corticosteroid combination therapy but whether dual bronchodilation improves cardiac function is unknown. METHODS: We did a double-blind, randomised, two-period crossover, placebo-controlled, single-centre study (CLAIM) at the Fraunhofer Institute of Toxicology and Experimental Medicine (Hannover, Germany), a specialty clinic...
February 21, 2018: Lancet Respiratory Medicine
Ying Wang, Xiaoxi Huang, Dong Leng, Jifeng Li, Lei Wang, Yan Liang, Jun Wang, Ran Miao, Tao Jiang
Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease which is often underpinned by vascular remodeling. Although pulmonary arterial smooth muscle cells (PASMCs) are the main participants in vascular remodeling, their biological role in CTEPH is not entirely clear. In this study, we analyzed the whole epigenome-wide DNA methylation profiles of cultured PASMCs from CTEPH and control cell lines using an Illumina HumanMethylation450K BeadChip. A total of 6829 significantly differentially methylated probes (DMPs) were detected between the two groups, of which 4246 DMPs were hypermethylated while 2583 DMPs were hypomethylated...
February 23, 2018: Physiological Genomics
Susan Pyne, David R Adams, Nigel J Pyne
There is substantial evidence that the enzymes, sphingosine kinase 1 and 2, which catalyse the formation of the bioactive lipid sphingosine 1-phosphate, are involved in pathophysiological processes. In this chapter, we appraise the evidence that both enzymes are druggable and describe how isoform-specific inhibitors can be developed based on the plasticity of the sphingosine-binding site. This is contextualised with the effect of sphingosine kinase inhibitors in cancer, pulmonary hypertension, neurodegeneration, inflammation and sickling...
February 20, 2018: Handbook of Experimental Pharmacology
Mette Calundann Noer, Pia Leandersson, Torbjørn Paulsen, Susanne Rosthøj, Sofie Leisby Antonsen, Christer Borgfeldt, Claus Høgdall
OBJECTIVE: Danish ovarian cancer (OC) patients have previously been found to have worse prognosis than Swedish patients, and comorbidity has been suggested as a possible explanation for this survival difference. We aimed to investigate the prognostic impact of comorbidity in surgically treated OC patients in Denmark and Sweden. METHODS: This comparative cohort study was based on data from 3118 surgically treated OC patients diagnosed in 2012-2015. The Swedish subcohort (n = 1472) was identified through the Swedish National Quality Register of Gynecological Surgery, whereas the Danish subcohort (n = 1646) originated from the Danish Gynecological Cancer Database...
February 16, 2018: Acta Oncologica
Wolfgang M Kuebler
No abstract text is available yet for this article.
February 13, 2018: American Journal of Respiratory and Critical Care Medicine
Fuqin Yan, Xiaomeng Sun, Chun Xu
Resveratrol is a flavonoid with a stilbene structure that is able to suppress acute pulmonary thromboembolism-induced pulmonary artery hypertension. Furthermore, it possesses anti-cancer and antioxidant properties, is able to regulate blood lipids and increase life expectancy. In the present study, it was evaluated whether the protective effect of resveratrol was able to improve cardiovascular function in rats with diabetes. The effects of resveratrol on blood glucose, body weight, heart/body weight ratio, plasma triglyceride levels, heart rate, aspartate transaminase (AST)/alanine transaminase (ALT) ratio and total plasma insulin were evaluated...
February 2018: Experimental and Therapeutic Medicine
Joana Bicker, Gilberto Alves, Ana Fortuna, Patrício Soares-da-Silva, Amílcar Falcão
Inhibition of the biosynthesis of noradrenaline is a currently explored strategy for the treatment of hypertension, congestive heart failure and pulmonary arterial hypertension. While some dopamine β-hydroxylase (DBH) inhibitors cross the blood-brain barrier (BBB) and cause central as well as peripheral effects (nepicastat), others have limited access to the brain (etamicastat, zamicastat). In this context, peripheral selectivity is clinically advantageous, in order to prevent alterations of noradrenaline levels in the CNS and the occurrence of adverse central effects...
February 8, 2018: European Journal of Pharmaceutical Sciences
J R Pharr, C A Coughenour, T J Bungum
OBJECTIVE: Obesity and physical inactivity are associated with increased rates of chronic diseases and conditions. However, the 'fit but fat' theory posits that cardiopulmonary fitness (or physical activity) can mitigate risks to health associated with obesity. The purpose of this study was to compare chronic diseases and conditions of highly active/obese women with inactive/normal weight women. STUDY DESIGN: This was a cross-sectional study of the 2015 Behavioral Risk Factor Surveillance System data...
February 7, 2018: Public Health
Itaru Matsumura
Tyrosine kinase inhibitors (TKIs) have significantly improved the clinical outcomes of patients with chronic myeloid leukemia (CML). However, patients with CML need to receive TKI therapy for several years. Hence, the safety of long-term TKI treatment warrants utmost attention. Among various adverse events caused by TKI therapy, cardiovascular events (CVEs), such as acute myocardial infarction, cerebral infarction, and pulmonary hypertension, are the most serious with high mortality. TKIs inhibit various off-target molecules involved in the occurrence of CVEs such as c-Kit, platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor (VEGFR), and Tie-2/Tec...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Feixiong Cheng, Joseph Loscalzo
Pulmonary hypertension (PH) is caused by many disorders that affect the pulmonary vasculature. A recent study has provided evidence that pulmonary vascular remodeling and PH can be observed in lung cancer, and this may be associated with tumor cell-immune cell inflammatory crosstalk. These findings highlight the pressing need to understand better and manage pulmonary vascular comorbidities in lung cancer.
February 1, 2018: Trends in Molecular Medicine
Olivier Boucherat, Thibaut Peterlini, Alice Bourgeois, Valérie Nadeau, Sandra Breuils-Bonnet, Stéphanie Boilet-Molez, François Potus, Jolyane Meloche, Sophie Chabot, Caroline Lambert, Eve Tremblay, Young Chan Chae, Dario C Altieri, Gopinath Sutendra, Evangelos D Michelakis, Roxane Paulin, Steeve Provencher, Sébastien Bonnet
RATIONALE: Pulmonary arterial hypertension (PAH) is a vascular remodeling disease with a poor prognosis and limited therapeutic option. Although the mechanisms contributing to vascular remodeling in PAH are still unclear, several features, including hyper-proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs), have led to the emergence of the cancer-like concept. The molecular chaperone heat shock protein 90 (HSP90) is directly associated with malignant growth and proliferation under stress conditions...
February 2, 2018: American Journal of Respiratory and Critical Care Medicine
Kurt R Stenmark, Maria G Frid, Brian B Graham, Rubin M Tuder
Pulmonary hypertension (PH) is the end result of interaction between pulmonary vascular tone and a complex series of cellular and molecular events termed "vascular remodeling". The remodeling process, which can involve the entirety of pulmonary arterial vasculature, almost universally involves medial thickening, driven by increased numbers and hypertrophy of its principal cellular constituent, smooth muscle cells (SMCs). It is noted, however that SMCs comprise heterogeneous populations of cells, which can exhibit markedly different proliferative, inflammatory, and extracellular matrix production changes during remodeling...
January 27, 2018: Cardiovascular Research
Matthias Totzeck, Raluca-Ileana Mincu, Simone Mrotzek, Dirk Schadendorf, Tienush Rassaf
Background Targeted therapy with tyrosine kinase inhibitors with anti-vascular endothelial growth factor activity improves survival of cancer patients. Cardiovascular complications are critical and it is unknown whether these require specific treatment strategies. We aimed to clarify the associated risk of cardiovascular adverse events in patients treated with tyrosine kinase inhibitors. Design The design of this study was a meta-analysis of randomised controlled trials. Methods We searched PubMed, Cochrane, EMBASE and Web of Science databases for randomised controlled trials published until January 2017 that assessed patients with different types of cancer treated with or without tyrosine kinase inhibitors in addition to standard chemotherapy...
January 1, 2018: European Journal of Preventive Cardiology
Ori Wand, Mordechai R Kramer
There is an increasing recognition of patients with radiologic features of both pulmonary fibrosis and emphysema. This association has enabled the description of a syndrome termed combined pulmonary fibrosis and emphysema (CPFE) with unique features. Patients are mostly male smokers who suffer from effort dyspnea and hypoxemia, with near-normal spirometric and lung volumes measurements, and abnormalities of gas exchange. On the computerized tomography there is upper-lobe emphysema and lower-lobe interstitial fibrosis...
January 2018: Harefuah
Jeffrey D Marshall, Isabel Bazan, Yi Zhang, Wassim H Fares, Patty J Lee
Pulmonary hypertension describes a heterogeneous disease defined by increased pulmonary artery pressures, and progressive increase in pulmonary vascular resistance due to pathologic remodeling of the pulmonary vasculature involving pulmonary endothelial cells, pericytes, and smooth muscle cells.  This process occurs under various conditions, and though these populations vary, the clinical manifestations are the same: progressive dyspnea, increases in right ventricular (RV) afterload and dysfunction, RV-pulmonary artery uncoupling, and right-sided heart failure with systemic circulatory collapse...
January 18, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
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