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Lung NET

Aimilia Exarchakou, Bernard Rachet, Aurélien Belot, Camille Maringe, Michel P Coleman
OBJECTIVE: To assess the effectiveness of the NHS Cancer Plan (2000) and subsequent national cancer policy initiatives in improving cancer survival and reducing socioeconomic inequalities in survival in England. DESIGN: Population based cohort study. SETTING: England. POPULATION: More than 3.5 million registered patients aged 15-99 with a diagnosis of one of the 24 most common primary, malignant, invasive neoplasms between 1996 and 2013...
March 14, 2018: BMJ: British Medical Journal
Juan A Muñoz-Largacha, Katrina A Steiling, Hasmeena Kathuria, Marjory Charlot, Carmel Fitzgerald, Kei Suzuki, Virginia R Litle
BACKGROUND: Safety net hospitals provide care mostly to low-income, uninsured, and vulnerable populations, in whom delays in cancer screening are established barriers. Socioeconomic barriers might pose important challenges to the success of a lung cancer screening program at a safety net hospital. We aimed to determine screening follow-up compliance, rates of diagnostic and treatment procedures, and the rate of cancer diagnosis in patients classified as category 4 by the Lung CT Screening Reporting and Data System (Lung-RADS 4)...
February 9, 2018: Journal of Thoracic and Cardiovascular Surgery
Mami Morita, Taku Sato, Miyuki Nomura, Yoshimi Sakamoto, Yui Inoue, Ryota Tanaka, Shigemi Ito, Koreyuki Kurosawa, Kazunori Yamaguchi, Yuki Sugiura, Hiroshi Takizaki, Yoji Yamashita, Ryuichi Katakura, Ikuro Sato, Masaaki Kawai, Yoshinori Okada, Hitomi Watanabe, Gen Kondoh, Shoko Matsumoto, Ayako Kishimoto, Miki Obata, Masaki Matsumoto, Tatsuro Fukuhara, Hozumi Motohashi, Makoto Suematsu, Masaaki Komatsu, Keiichi I Nakayama, Toshio Watanabe, Tomoyoshi Soga, Hiroshi Shima, Makoto Maemondo, Nobuhiro Tanuma
Expression of PKM2, which diverts glucose-derived carbon from catabolic to biosynthetic pathways, is a hallmark of cancer. However, PKM2 function in tumorigenesis remains controversial. Here, we show that, when expressed rather than PKM2, the PKM isoform PKM1 exhibits a tumor-promoting function in KRASG12D -induced or carcinogen-initiated mouse models or in some human cancers. Analysis of Pkm mutant mouse lines expressing specific PKM isoforms established that PKM1 boosts tumor growth cell intrinsically. PKM1 activated glucose catabolism and stimulated autophagy/mitophagy, favoring malignancy...
March 12, 2018: Cancer Cell
Fabia Wyss, Martin Schneiter, Udo Hetzel, Fta Pathologie, Saskia Keller, Martin Frenz, Jaroslav Rička, Jean-Michel Hatt
Pneumonia is a common complication of boid inclusion body disease (BIBD) in snakes. The tracheal mucociliary apparatus of eight boas ( Boa constrictor) and two pythons ( Python regius, Morelia viridis) was examined to assess whether absent or reduced mucociliary clearance could be a predisposing factor. Nine of the examined snakes were positive for BIBD by detection of inclusion bodies and three had lung pathologies other than the formation of inclusion bodies. A considerable individual variation of ciliary beat frequency (CBF, 3...
March 2018: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
Ahmed Moghieb, Geremy Clair, Hugh Mitchell, Joseph A Kitzmiller, Erika M Zink, Young-Mo Kim, Vladislav Petyuk, Anil K Shukla, Ronald J Moore, Thomas O Metz, James P Carson, Jason E McDermott, Richard A Corley, Jeffrey A Whitsett, Charles Ansong
Biochemical networks mediating normal lung morphogenesis and function have important implications for ameliorating morbidity and mortality in premature infants. While several transcript-level studies have examined normal lung development, corresponding protein-level analyses are lacking. Here we performed proteomics analysis of murine lungs from embryonic to early adult ages to identify the molecular networks mediating normal lung development. We identified 8,932 proteins providing a deep and comprehensive view of the lung proteome...
March 8, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Jon M Florence, Agnieszka Krupa, Laela M Booshehri, Sandra A Davis, Michael A Matthay, Anna K Kurdowska
Infection with seasonal influenza A virus (IAV) leads to lung inflammation and respiratory failure, a main cause of death in influenza infected patients. Previous experiments in our laboratory indicated that Bruton's tyrosine kinase (Btk) plays a substantial role in regulating inflammation in the respiratory region during acute lung injury (ALI) in mice, therefore we sought to determine if blocking Btk activity had a protective effect in the lung during influenza induced inflammation. A Btk inhibitor (Btk Inh...
March 8, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Naveen Gupta, Roland Liu, Stephanie Shin, Ranjeet Sinha, Joseph Pogliano, Kit Pogliano, John H Griffin, Victor Nizet, Ross Corriden
Objectives: The role of protease-activated receptor 1 (PAR1) in the pathogenesis of pneumonia and sepsis is ambiguous given the existing literature. As PAR1 is classically activated by the coagulation-based protease thrombin and leads to vascular leakage, our hypothesis was that PAR1 blockade with SCH79797 would be therapeutically beneficial in an experimental model of murine Gram-negative pneumonia. Methods: In this study, we administered SCH79797 via the intrapulmonary route 6 h after the establishment of Escherichia coli pneumonia and observed a significant improvement in survival, lung injury, bacterial clearance and inflammation...
March 5, 2018: Journal of Antimicrobial Chemotherapy
Michael S Broder, Beilei Cai, Eunice Chang, Maureen P Neary, Elya Papoyan, Al B Benson Iii
OBJECTIVE: The aim of this study was to describe real-world lung neuroendocrine tumor (NET) treatment patterns. METHODS: This study examined cytotoxic chemotherapy (CC), somatostatin analogues (SSA), targeted therapy (TT), interferon, and liver-directed therapies in 2 US claims databases. Patients ≥18 years with ≥1 inpatient or ≥2 outpatient claims for lung NET, initiating pharmacologic treatment between July 1, 2009, and June 30, 2014, were identified and followed until the end of enrollment or study end, whichever occurred first...
March 6, 2018: Oncology
Anusha M Vable, Mathew V Kiang, Sanjay Basu, Kara E Rudolph, Ichiro Kawachi, S V Subramanian, M Maria Glymour
Background: Military service is associated with smoking initiation, but U.S. veterans are also eligible for special social, financial, and healthcare benefits, which are associated with smoking cessation. A key public health question is how these offsetting pathways affect health disparities; we assessed the net effects of military service on later life pulmonary function among Korean War era veterans by childhood socio-economic status (cSES). Methods: Data came from U...
March 2, 2018: Military Medicine
A Chua, A Perrin, J F Ricci, M P Neary, M Thabane
Background: In 2016, everolimus was approved by Health Canada for the treatment of unresectable, locally advanced or metastatic, well-differentiated, non-functional, neuroendocrine tumours (NET) of gastrointestinal (GI) or lung origin in adult patients with progressive disease. This analysis evaluated the cost-effectiveness of everolimus in this setting from a Canadian societal perspective. Methods: A partitioned survival model was developed to compare the cost per life-year (LY) gained and cost per quality-adjusted life-year (QALY) gained of everolimus plus best supportive care (BSC) versus BSC alone in patients with advanced or metastatic NET of GI or lung origin...
February 2018: Current Oncology
Yuji Yamada, Ananda Chowdhury, Joel P Schneider, William G Stetler-Stevenson
Tissue Inhibitor of Metalloproteinase 2 (TIMP-2), is an endogenous 22 kDa proteinase inhibitor, demonstrating anti-tumorigenic, anti-metastatic and anti-angiogenic activities in vitro and in vivo. Recombinant TIMP-2 is currently undergoing preclinical testing in multiple, murine tumor models. Here we report the development of an inert, injectable peptide hydrogel matrix enabling encapsulation and sustained release of TIMP-2. We studied the TIMP-2 release profile from four ß-hairpin peptide gels of varying net electrostatic charge...
March 5, 2018: Biomacromolecules
Dimitrios Moris, Ioannis Ntanasis-Stathopoulos, Diamantis I Tsilimigras, Mohamad A Adam, Chifu Jeffrey Yang, David Harpole, Stamatios Theocharis
Primary lung neuroendocrine tumors (NETs) consist of typical and atypical carcinoids, large-cell neuroendocrine carcinomas and small-cell lung carcinomas. NETs are highly heterogeneous in histological characteristics, clinical presentation and natural history. While there are morphological and immunohistochemical criteria to establish diagnosis, there is a lack of universal consensus for prognostic factors or therapeutic targets for personalized treatment of the disease. Thus, identifying potential markers of neuroendocrine differentiation and prognostic factors remains of high importance...
March 2018: Cancer Genomics & Proteomics
Luis Morales Quinteros, Josep Bringué Roque, David Kaufman, Antonio Artigas Raventós
Important recent insights have emerged regarding the cellular and molecular role of carbon dioxide (CO2 ) and the effects of hypercapnia. The latter may have beneficial effects in patients with acute lung injury, affording reductions in pulmonary inflammation, lessened oxidative alveolar damage, and the regulation of innate immunity and host defenses by inhibiting the expression of inflammatory cytokines. However, other studies suggest that CO2 can have deleterious effects upon the lung, reducing alveolar wound repair in lung injury, decreasing the rate of reabsorption of alveolar fluid, and inhibiting alveolar cell proliferation...
February 24, 2018: Medicina Intensiva
Lisa Bodei, Mark S Kidd, Aviral Singh, Wouter A van der Zwan, Stefano Severi, Ignat A Drozdov, Jaroslaw Cwikla, Richard P Baum, Dik J Kwekkeboom, Giovanni Paganelli, Eric P Krenning, Irvin M Modlin
BACKGROUND: Peptide receptor radionuclide therapy (PRRT) utilizes somatostatin receptor (SSR) overexpression on neuroendocrine tumors (NET) to deliver targeted radiotherapy. Intensity of uptake at imaging is considered related to efficacy but has low sensitivity. A pretreatment strategy to determine individual PRRT response remains a key unmet need. NET transcript expression in blood integrated with tumor grade provides a PRRT predictive quotient (PPQ) which stratifies PRRT "responders" from "non-responders"...
February 26, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Yan Zhang, Changyuan Wang, Zhihao Liu, Qiang Meng, Xiaokui Huo, Qi Liu, Pengyuan Sun, Xiaobo Yang, Huijun Sun, Xiaodong Ma, Kexin Liu
BACKGROUND: Afatinib is an irreversible multi-targeted TKI, used in the treatment with EGFR mutated non-small cell lung cancer (NSCLC). The purpose of this study is to explore the molecular pharmacokinetic mechanism underlying the effect of P-gp inhibitors on the intestinal absorption and biliary excretion and to understand how P-gp inhibitors affect afatinib pharmacokinetics. METHODS: Pharmacokinetics in vivo, in situ intestinal perfusion, perfused rat liver in situ, Caco-2 cells, P-gp ATPase activity, sandwich-cultured rat hepatocytes (SCRH) and transfected-cell transport were used in the evaluation...
November 4, 2017: Pharmacological Reports: PR
Renda Soylemez Wiener, Elisa Koppelman, Rendelle Bolton, Karen E Lasser, Belinda Borrelli, David H Au, Christopher G Slatore, Jack A Clark, Hasmeena Kathuria
BACKGROUND: Guidelines recommend, and Medicare requires, shared decision-making between patients and clinicians before referring individuals at high risk of lung cancer for chest CT screening. However, little is known about the extent to which shared decision-making about lung cancer screening is achieved in real-world settings. OBJECTIVE: To characterize patient and clinician impressions of early experiences with communication and decision-making about lung cancer screening and perceived barriers to achieving shared decision-making...
February 21, 2018: Journal of General Internal Medicine
Mark Kidd, Irvin M Modlin, Ignat Drozdov, Harry Aslanian, Lisa Bodei, Somer Matar, Kyung-Min Chung
No effective blood biomarker exists to detect and clinically manage bronchopulmonary (BP) neuroendocrine tumors (NET). We developed a blood-based 51 NET-specific transcript set for diagnosis and monitoring and evaluated clinical performance metrics. It accurately diagnosed the tumor and differentiated stable from progressive disease as determined by RECIST criteria. Gene expression was evaluated in: a) publicly available BPNET transcriptomes (GSE35679); b) two BPNET cell-lines; and c) BPNET tissue with paired blood ( n = 7)...
January 23, 2018: Oncotarget
Donghwa Kim, Soomin Cho, Jung A Woo, Stephen B Liggett
β2 -Adrenergic receptors (β2 ARs) desensitize during continuous agonist activation, which manifests clinically as tachyphylaxis. β-Agonist desensitization of β2 ARs in human airway smooth muscle (HASM) cells is recognized in the treatment of asthma and may be related to poor outcomes. Rapid events in desensitization include receptor phosphorylation and internalization, but mechanisms responsible for the decrease in receptor protein after prolonged agonist exposure (down-regulation) are ill defined. The microRNA (miRNA) let-7f regulates β2 AR expression by translational repression...
February 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Adam Leigh, John W McEvoy, Parveen Garg, J Jeffrey Carr, Veit Sandfort, Elizabeth C Oelsner, Matthew Budoff, David Herrington, Joseph Yeboah
OBJECTIVES: This study assessed the utility of the pooled cohort equation (PCE) and/or coronary artery calcium (CAC) for atherosclerotic cardiovascular disease (ASCVD) risk assessment in smokers, especially those who were lung cancer screening eligible (LCSE). BACKGROUND: The U.S. Preventive Services Task Force recommended and the Centers for Medicare & Medicaid Services currently pays for annual screening for lung cancer with low-dose computed tomography scans in a specified group of cigarette smokers...
February 9, 2018: JACC. Cardiovascular Imaging
Hyun S Kim, Walid L Shaib, Chao Zhang, Ganji Purnachandra Nagaraju, Christina Wu, Olatunji B Alese, Zhengjia Chen, Edith Brutcher, Meredith Renfroe, Bassel F El-Rayes
BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2...
February 16, 2018: Cancer
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