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Pulmonary hypertension and cancer

Margaret O James, Stephan C Jahn, Guo Zhong, Marci G Smeltz, Zhiwei Hu, Peter W Stacpoole
Dichloroacetate (DCA) has several therapeutic applications based on its pharmacological property of inhibiting pyruvate dehydrogenase kinase. DCA has been used to treat inherited mitochondrial disorders that result in lactic acidosis, as well as pulmonary hypertension and several different solid tumors, the latter through its ability to reverse the Warburg effect in cancer cells and restore aerobic glycolysis. The main clinically limiting toxicity is reversible peripheral neuropathy. Although administration of high doses to rodents can result in liver cancer, there is no evidence that DCA is a human carcinogen...
October 19, 2016: Pharmacology & Therapeutics
Francesco Cavallin, Marco Scarpa, Matteo Cagol, Rita Alfieri, Alberto Ruol, Vanna Chiarion Sileni, Ermanno Ancona, Carlo Castoro
OBJECTIVE: The aim of this study was to investigate trends in patients' characteristics and comorbidities in esophageal cancer (EC) patients. BACKGROUND: Identifying changing pattern is essential to understand and predict further changes and to plan surgical procedures and resource allocation. METHODS: Trends in patients' characteristics and comorbidities were evaluated in 4440 EC patients at the Center for Esophageal Diseases in Padova, Italy, during 1980 to 2011...
October 17, 2016: Annals of Surgery
Elizabeth M Gordon, Debbie M Figueroa, Amisha V Barochia, Xianglan Yao, Stewart J Levine
Apolipoprotein A-I (apoA-I) and high-density lipoproteins (HDL) mediate reverse cholesterol transport out of cells. Furthermore, HDL has additional protective functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and vasoprotective effects. In contrast, HDL can become dysfunctional with a reduction in both cholesterol efflux and anti-inflammatory properties in the setting of disease or the acute phase response. These paradigms are increasingly being recognized to be active in the pulmonary system, where apoA-I and HDL have protective effects in normal lung health, as well as in a variety of disease states, including acute lung injury (ALI), asthma, chronic obstructive pulmonary disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and viral pneumonia...
2016: Frontiers in Pharmacology
Chun-Chao Chen, Yi-Ping Hsu, Ju-Chi Liu, Pai-Feng Kao, Li-Chin Sung, Chao-Feng Lin, Wen-Rui Hao, Shing-Hwa Liu, Szu-Yuan Wu
PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with an increased cancer risk. We evaluated the chemopreventive effect of statins against all cancers in COPD patients and identified the statin with the strongest chemopreventive effect. PATIENTS AND METHODS: All patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) from January 1, 2001, to December 31, 2012, were recruited. Each patient was followed to assess the following protective and risk factors for all cancers: age; sex; comorbidities (diabetes, hypertension, dyslipidemia) and the Charlson comorbidity index [CCI]); urbanization level; monthly income; and nonstatin drug use...
2016: Journal of Cancer
Xiaowei Gong, Haiyan Wang, Yadong Yuan
The present study aimed to investigate the factors affecting the first therapeutic-target-achieving (TTA) time of warfarin therapy in patients with acute pulmonary embolism (PTE). Between January 2008 and June 2013, patients with PTE confirmed by transpulmonary arterial enhanced computed tomographic pulmonary angiography or pulmonary ventilation perfusion scanning were included in the present study. Data collected included demographic information, history of tobacco and alcohol intake, basic diseases (stable and unstable hypertension, diabetes, heart failure, cancer/cerebral infarction, old myocardial infarction and atrial fibrillation), liver and kidney function, the haemoglobin and platelet count of the blood, international normalized ratio monitoring, warfarin dosage adjustment and medication combinations...
October 2016: Experimental and Therapeutic Medicine
Keytam S Awad, James D West, Vinicio de Jesus Perez, Margaret MacLean
The proliferative endothelial and smooth muscle cell phenotype, inflammation, and pulmonary vascular remodeling are prominent features of pulmonary arterial hypertension (PAH). Mutations in bone morphogenetic protein type 2 receptor (BMPR2) have been identified as the most common genetic cause of PAH and females with BMPR2 mutations are 2.5 times as likely to develop heritable forms of PAH than males. Higher levels of estrogen have also been observed in males with PAH, implicating sex hormones in PAH pathogenesis...
September 2016: Pulmonary Circulation
Jessica H Huston, John J Ryan
Epigenetics is an emerging field of research and clinical trials in cancer therapy that also has applications for pulmonary arterial hypertension (PAH), as there is evidence that epigenetic control of gene expression plays a significant role in PAH. The three types of epigenetic modification include DNA methylation, histone modification, and RNA interference. All three have been shown to be involved in the development of PAH. Currently, the enzymes that perform these modifications are the primary targets of neoplastic therapy...
September 2016: Pulmonary Circulation
Jaganmay Sarkar, Suman Kumar Nandy, Animesh Chowdhury, Tapati Chakraborti, Sajal Chakraborti
Green tea polyphenolic catechins have been shown to prevent various types of diseases such as pulmonary hypertension (PAH), cancer and cardiac and neurological disorders. Matrix metalloproteinases (MMPs) play an important role in the development of PAH. The present study demonstrated that among the four green tea catechins (EGCG, ECG, EC and EGC), EGCG and ECG inhibit pro-/active MMP-9 activities in pulmonary artery smooth muscle cell culture supernatant. Based on the above, we investigated the interactions of pro-/active MMP-9 with the green tea catechins by computational methods...
September 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Kathleen Atkins, Asish Dasgupta, Kuang-Hueih Chen, Jeff Mewburn, Stephen L Archer
Mitochondrial morphology is governed by the balance of mitochondrial fusion, mediated by mitofusins and optic atrophy 1 (OPA1), and fission, mediated by dynamin-related protein 1 (Drp1). Disordered mitochondrial dynamics alters metabolism, proliferation, apoptosis and mitophagy, contributing to human diseases, including neurodegenerative syndromes, pulmonary arterial hypertension (PAH), cancer and ischemia/reperfusion injury. Post-translational regulation of Drp1 (by phosphorylation and SUMOylation) is an established means of modulating Drp1 activation and translocation to the outer mitochondrial membrane (OMM)...
November 1, 2016: Clinical Science (1979-)
Ippei Fukada, Kazuhiro Araki, Kokoro Kobayashi, Tomoko Shibayama, Masaru Hatano, Shunji Takahashi, Takuji Iwase, Shinji Ohno, Yoshinori Ito
INTRODUCTION: Pulmonary tumor thrombotic microangiopathy (PTTM) is rare, cancer-related pulmonary complication leading to hypoxia, pulmonary hypertension, and heart failure. The standard treatment for PTTM is not established. However, imatinib, a tyrosine kinase inhibitor of the PDGF receptor, may cause regression of pulmonary hypertension and pulmonary artery remodeling in PTTM. CASE DESCRIPTIONS: We report two cases of PTTM who received an anti-PDGF agent of imatinib for PTTM developed during chemotherapy for metastatic breast cancer...
2016: SpringerPlus
Zhigang Hong, Kuang-Hueih Chen, Asish Dasgupta, Francois Potus, Kimberly Dunham-Snary, Sebastien Bonnet, Lian Tian, Jennifer Fu, Sandra Breuils-Bonnet, Steeve Provencher, Danchen Wu, Jeffrey Mewburn, Mark L Ormiston, Stephen L Archer
RATIONALE: Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy characterized by excessive pulmonary artery smooth muscle cells (PASMC) proliferation, migration, and apoptosis-resistance. This cancer-like phenotype is promoted by increased cytosolic calcium ([Ca2+]cyto), aerobic glycolysis and mitochondrial fission. OBJECTIVES: To determine how changes in mitochondrial calcium uniporter complex (MCUC) function influence mitochondrial dynamics and contribute to PAH's cancer-like phenotype...
September 20, 2016: American Journal of Respiratory and Critical Care Medicine
E Bravos, S Bayle-Bleuez, A Wahart, R Lachèze, F Forest, J-B Guichard, L Bertoletti
A 60-year-old patient was under follow-up for pulmonary hypertension consistent with pulmonary veno-occlusive disease. During his follow-up, a parenchymal opacity was discovered. We describe the management of the suspicion of lung cancer, highlighting the modification of the conventional diagnostic and therapeutic strategy on account of the pulmonary hypertension. Chest physicians should be able to adapt their diagnostic and therapeutic management in the case of neoplasia in patients with severe pulmonary hypertension...
September 13, 2016: Revue des Maladies Respiratoires
Soni Savai Pullamsetti, Rajkumar Savai, Werner Seeger, Elena A Goncharova
Pulmonary arterial hypertension (PAH) is a progressive and rapidly fatal disease with a high mortality rate. PAH manifests by proliferation/apoptosis imbalance of pulmonary vascular cells leading to remodeling of small pulmonary arteries (PA), increased PA pressure, elevated right ventricular afterload, right heart failure and death. Emerging evidence from many research groups indicates that PAH may be viewed as a proliferative disease with a cancer-like nature and shares an incredible number of pathogenic signaling mechanisms with human cancers...
September 14, 2016: American Journal of Respiratory and Critical Care Medicine
Rodrigo Rodriguez-Fernandez, Nawi Ng, Dwidjo Susilo, John Prawira, Michael J Bangs, Rachel M Amiya
BACKGROUND: As the global shift toward non-communicable diseases overlaps with the unfinished agenda of confronting infectious diseases in low- and middle-income countries, epidemiological links across both burdens must be recognized. This study examined the non-communicable disease-infectious disease overlap in the specific comorbidity rates for key diseases in an occupational cohort in Papua, Indonesia. METHODS: Diagnosed cases of ischaemic heart disease, stroke, hypertension, diabetes (types 1 and 2), chronic obstructive pulmonary disease, asthma, cancer, HIV and AIDS, tuberculosis, and malaria were extracted from 22,550 patient records (21,513 men, 1037 women) stored in identical electronic health information systems from two clinic sites in Papua, Indonesia...
2016: BMC Public Health
Christopher S King, Steven D Nathan
Despite the development of pharmacological therapies that are effective in slowing the progression of idiopathic pulmonary fibrosis (IPF), it remains a debilitating and lethal condition. In addition to the adverse effects caused by pulmonary fibrosis, most patients with IPF have associated comorbid conditions, which might negatively affect functional status, quality of life, and survival. Comorbid conditions can be pulmonary or extrapulmonary. Pulmonary comorbidities include pulmonary hypertension, emphysema, and lung cancer, while non-pulmonary conditions include venous thromboembolism, coronary artery disease, congestive heart failure, sleep-disordered breathing, gastro-oesophageal reflux disease, and anxiety or depression...
September 2, 2016: Lancet Respiratory Medicine
Keaton Piper, Hanna Algattas, Ian A DeAndrea-Lazarus, Kristopher T Kimmell, Yan Michael Li, Kevin A Walter, Howard J Silberstein, G Edward Vates
OBJECTIVE Patients undergoing spinal surgery are at risk for developing venous thromboembolism (VTE). The authors sought to identify risk factors for VTE in these patients. METHODS The American College of Surgeons National Surgical Quality Improvement Project database for the years 2006-2010 was reviewed for patients who had undergone spinal surgery according to their primary Current Procedural Terminology code(s). Clinical factors were analyzed to identify associations with VTE. RESULTS Patients who underwent spinal surgery (n = 22,434) were identified...
September 2, 2016: Journal of Neurosurgery. Spine
Dario Nieri, Tommaso Neri, Silvia Petrini, Barbara Vagaggini, Pierluigi Paggiaro, Alessandro Celi
Cell-derived microparticles are small (0.1-1 μm) vesicles shed by most eukaryotic cells upon activation or during apoptosis. Microparticles carry on their surface, and enclose within their cytoplasm, molecules derived from the parental cell, including proteins, DNA, RNA, microRNA and phospholipids. Microparticles are now considered functional units that represent a disseminated storage pool of bioactive effectors and participate both in the maintenance of homeostasis and in the pathogenesis of diseases. The mechanisms involved in microparticle generation include intracellular calcium mobilisation, cytoskeleton rearrangement, kinase phosphorylation and activation of the nuclear factor-κB...
September 2016: European Respiratory Review: An Official Journal of the European Respiratory Society
Patricia Lozano-Cruz, David Vivas, Alexis Rojas, Rebeca Font, Feliciano Román-García, Benjamín Muñoz
BACKGROUND AND OBJECTIVE: Pulmonary thromboembolism (PTE) is a very common condition with high mortality. Although some scales include heart failure (HF) as a risk factor of PTE, none of them have assessed the contribution of the different kinds of HF, i. e. with reduced or preserved left ventricular ejection fraction (LVEF) to the in-hospital outcome of patients admitted with PTE. PATIENTS AND METHOD: A retrospective study assessing a cohort of patients consecutively admitted to hospital with a PTE from 2012-2014...
October 21, 2016: Medicina Clínica
Aya Banno, Keijiro Chiba, Hiroko Kasai, Keiichi Nagami
Pulmonary tumour thrombotic microangiopathy (PTTM) resulting in fatal pulmonary hypertension is a rare complication of malignancy. Patients with PTTM generally suffer rapid deterioration of hypoxaemia, and a diagnosis is often only made at autopsy. We report a case of extramammary Paget's disease associated with PTTM. An ante-mortem diagnosis was made based on cytology of blood aspirated from a pulmonary artery catheter in a wedged position. Together with a review of the literature, this case highlights the potential diagnostic value of blood cytology in patients with cancer with rapidly progressing pulmonary hypertension...
2016: BMJ Case Reports
Ju-Chi Liu, Tsung-Yeh Yang, Yi-Ping Hsu, Wen-Rui Hao, Pai-Feng Kao, Li-Chin Sung, Chun-Chao Chen, Szu-Yuan Wu
PURPOSE: Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk. We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential. RESULTS: After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0...
August 9, 2016: Oncotarget
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