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Kwangwoo Park, Sungjin Park, Mi-Jin Jeon, Jinhyun Choi, Jun Won Kim, Yoon Jin Cho, Won-Seok Jang, Yo Sup Keum, Ik Jae Lee
The 3D-printed boluses were used during the radiation therapy of the chest wall in six patients with breast cancer after modified radical mastectomy (MRM). We measured the in-vivo skin doses while both conventional and 3D-printed boluses were placed on the chest wall and compared the mean doses delivered to the ipsilateral lung and the heart. The homogeneity and conformity of the dose distribution in the chest wall for both types of boluses were also evaluated. The uniformity index on the chest skin was improved when the 3D-printed boluses were used, with the overall average skin dose being closer to the prescribed one in the former case (-0...
October 23, 2016: Oncotarget
Shyam Nyati, Areeb Chator, Katerina Schinske, Brandon S Gregg, Brian Dale Ross, Alnawaz Rehemtulla
The sterile alpha motif and leucine zipper containing kinase ZAK (AZK, MLT, MLK7), is a MAPK-kinase kinase (MKKK). Like most MAPKKKs which are known to activate the c-Jun. amino-terminal kinase (JNK) pathway, ZAK has been shown to participate in the transduction of Transforming growth factor-β (TGF-β)-mediated non-canonical signaling. A role for ZAK in SMAD-dependent, canonical TGF-β signaling has not been previously appreciated. Using a combination of functional genomics and biochemical techniques, we demonstrate that ZAK regulates canonical TGFβRI/II signaling in lung and breast cancer cell lines and may serve as a key node in the regulation of TGFBR kinase activity...
October 23, 2016: Translational Oncology
Ju Hui Jeong, Yong Jin Oh, Yunmee Lho, Sun You Park, Kwang-Hyeon Liu, Eunyoung Ha, Young Ho Seo
The molecular chaperone Hsp90 plays an important role in cancer cell survival and proliferation by regulating the maturation and stabilization of numerous oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 has emerged as an attractive therapeutic target for cancer treatment. In this study, the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors are described. Among the synthetic compounds, 6,7-dihydrothieno [3,2-c]pyridin-5(4H)-yl amide 19 exhibits a remarkable binding affinity to the N-terminus of Hsp90 in a fluorescence polarization (FP) binding assay (IC50 = 50...
October 18, 2016: European Journal of Medicinal Chemistry
Vanessa I S Mendes, Geoffrey A Bartholomeusz, Mary Ayres, Varsha Gandhi, Jorge A R Salvador
No abstract text is available yet for this article.
October 23, 2016: European Journal of Medicinal Chemistry
(no author information available yet)
Background Long-term treatment with supplemental oxygen has unknown efficacy in patients with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation. Methods We originally designed the trial to test whether long-term treatment with supplemental oxygen would result in a longer time to death than no use of supplemental oxygen among patients who had stable COPD with moderate resting desaturation (oxyhemoglobin saturation as measured by pulse oximetry [Spo2], 89 to 93%)...
October 27, 2016: New England Journal of Medicine
Patrick T Walsh, Padraic G Fallon
The recently discovered interleukin (IL)-36 family of cytokines form part of the broader IL-1 family and are emerging as important mediators of inflammatory disease. The IL-36 subfamily consists of three ligands-IL-36α, IL-36β, and IL-36γ-and the natural antagonist IL-36Ra. The cytokines exert their effects through a specific IL-36 receptor consisting of IL-36R and IL-1RAcP chains. IL-36 cytokines can direct both innate and adaptive immune responses by acting on parenchymal, stromal, and specific immune cell subsets...
October 26, 2016: Annals of the New York Academy of Sciences
Hirokazu Taniguchi, Shinji Takeuchi, Koji Fukuda, Takayuki Nakagawa, Sachiko Arai, Shigeki Nanjo, Tadaaki Yamada, Hiroyuki Yamaguchi, Hiroshi Mukae, Seiji Yano
Crizotinib, a first-generation anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor, is known to be effective against echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive non-small cell lung cancers. Nonetheless, the tumors subsequently become resistant to crizotinib and recur in almost every case. The mechanism of the acquired resistance needs to be deciphered. In this study, we established crizotinib-resistant cells (A925LPE3-CR) via long-term administration of crizotinib to a mouse model of pleural carcinomatous effusions; this model involved implantation of the A925LPE3 cell line, which harbors the EML4-ALK gene rearrangement...
October 26, 2016: Cancer Science
Satyanarayana Swamy Cheekatla, Deepak Tripathi, Sambasivan Venkatasubramanian, Pavan Kumar Nathella, Padmaja Paidipally, Munenori Ishibashi, Elwyn Welch, Amy R Tvinnereim, Mitsuo Ikebe, Vijaya Lakshmi Valluri, Subash Babu, Hardy Kornfeld, Ramakrishna Vankayalapati
In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice...
October 2016: PLoS Pathogens
Chung-Sheng Shi, Tzu-Hsiung Huang, Chin-Kuo Lin, Jhy-Ming Li, Mei-Hsin Chen, Mei-Ling Tsai, Chih-Ching Chang
BACKGROUND: Mechanical ventilation is a life-saving procedure for patients with acute respiratory failure, although it may cause pulmonary vascular inflammation and leakage, leading to ventilator-induced lung injury (VILI). Ly6C+high monocytes are involved in the pathogenesis of VILI. In this study, we investigated whether pulmonary infiltrated Ly6C+high monocytes produce vascular endothelial growth factor (VEGF) and contribute to VILI. METHODS: A clinically relevant two-hit mouse model of VILI, with intravenous lipopolysaccharide (LPS, 20 ng/mouse) immediately before high tidal volume (HTV, 20 mL/kg) ventilation (LPS+HTV), was established...
2016: PloS One
Elie El Agha, Werner Seeger, Saverio Bellusci
Fibroblast growth factors (FGFs) constitute a large family of polypeptides that are involved in many biological processes, ranging from prenatal cell-fate specification and organogenesis to hormonal and metabolic regulation in postnatal life. During embryonic development, these growth factors are important mediators of the crosstalk among ectoderm, mesoderm and endoderm-derived cells and they instruct the spatial and temporal growth of organs and tissues such as the brain, bone, lung, gut etc. The involvement of FGFs in postnatal lung homeostasis is a growing field and there is emerging literature about their roles in lung pathophysiology...
October 26, 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Marlon E F Wilsterman, Pauline de Jager, Robert Blokpoel, Inez Frerichs, Sandra K Dijkstra, Marcel J I J Albers, Johannes G M Burgerhof, Dick G Markhorst, Martin C J Kneyber
BACKGROUND: Neuromuscular blockade (NMB) has been shown to improve outcome in acute respiratory distress syndrome (ARDS) in adults, challenging maintaining spontaneous breathing when there is severe lung injury. We tested in a prospective physiological study the hypothesis that continuous administration of NMB agents in mechanically ventilated children with severe acute hypoxemic respiratory failure (AHRF) improves the oxygenation index without a redistribution of tidal volume V T toward non-dependent lung zones...
December 2016: Annals of Intensive Care
Pablo Blanco, Giovanni Volpicelli
BACKGROUND: Point-of-care ultrasonography (POCUS) is a widely used tool in emergency and critical care settings, useful in the decision-making process as well as in interventional guidance. While having an impressive diagnostic accuracy in the hands of highly skilled operators, inexperienced practitioners must be aware of some common misinterpretations that may lead to wrong decisions at the bedside. OBJECTIVES: This article provides a revision list of common POCUS misdiagnoses usually found in practice and offers useful tips to recognize and avoid them...
December 2016: Critical Ultrasound Journal
Elena Lopez-Rodriguez, Gemma Gay-Jordi, Adele Mucci, Nico Lachmann, Anna Serrano-Mollar
Lung surfactant is a complex mixture of lipids and proteins lining the alveolar epithelium. At the air-liquid interface, surfactant lowers surface tension, avoiding alveolar collapse and reducing the work of breathing. The essential role of lung surfactant in breathing and therefore in life, is highlighted by surfactant deficiency in premature neonates, which causes neonatal respiratory distress syndrome and results in early death after birth. In addition, defects in surfactant metabolism alter lung homeostasis and lead to disease...
October 25, 2016: Cell and Tissue Research
Bartosz Kazimierz Słowikowski, Margarita Lianeri, Paweł Piotr Jagodziński
It is well known that a connection between xenobiotics inhalation, especially tobacco combustion and Lung Cancer development is strongly significant and indisputable. However, recent studies provide evidence indicating that another factors such as, estrogens are also involved in lung carcinoma biology and metabolism. Although the status of estrogen receptors (ER), in both cancerous and healthy lung tissue has been well documented, there is still inconclusive data with respect of which isoform of the receptor is present in the lungs...
October 25, 2016: Molecular Biology Reports
Satoshi Makita, Kenitiro Kaneko, Yasuyuki Ono, Hiroo Uchida
PURPOSE: We aimed to identify the risk factors for thoracic and spinal deformities following lung resection during childhood and to elucidate whether thoracoscopic surgery reduces the risk of complications after lung resection. METHODS: We retrospectively examined the medical records of all pediatric patients who underwent lung resection for congenital lung disease at our institution between 1989 and 2014. RESULTS: Seventy-four patients underwent lung resection during the study period and were followed-up...
October 25, 2016: Surgery Today
May Garrett, Timothy Taylor, Diane R Mould, Michael A Amantea, Ying Chen, Antonella Ingrosso, Yazdi K Pithavala
PURPOSE: Axitinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors 1-3, is approved for second-line treatment of advanced renal cell carcinoma. Axitinib is partially metabolized by cytochrome P450 1A2, which is induced by chronic heavy smoking. The effect of smoking on axitinib pharmacokinetics was evaluated in a non-small-cell lung cancer (NSCLC) patient population with a large number of active and ex-smokers. METHODS: Data were pooled from six clinical studies-serial pharmacokinetics from two healthy volunteer studies (n = 58) and sparse pharmacokinetics from four NSCLC studies (n = 152)-for a nonlinear mixed effects modeling (NONMEM v7...
October 25, 2016: Cancer Chemotherapy and Pharmacology
Christophe Walgraeve, Patrick De Wispelaere, Fé Van der Elst, Herman Van Langenhove
An analytical method was developed and optimized for the quantification of 16 polycyclic aromatic hydrocarbons (PAHs) and 12 oxygenated PAHs in Taxus baccata leaves. Emphasis was given to the development of an in-cell cleanup step using pressurized solvent extraction, a cleanup step using solid-phase extraction, and the instrumental analysis by GC-HRMS. Different extraction temperatures (between 50 and 200 °C) and Florisil quantities were evaluated for the extraction process. Based on the evaluation of both recoveries and matrix effect factors, a temperature of 200 °C and 1 g Florisil was selected as the optimum...
October 25, 2016: Analytical and Bioanalytical Chemistry
Christina Schröder, Rita Engenhart-Cabillic, Hilke Vorwerk, Michael Schmidt, Winfried Huhnt, Eyck Blank, Dietrich Sidow, André Buchali
PURPOSE: Using prospectively collected patient-related, dose-related, and pulmonary function test (PFT) data before radiotherapy (RT) and at several follow-up visits after RT, the time course of PFT changes after high-dose radio(chemo)therapy and influencing factors were analyzed. MATERIALS AND METHODS: From April 2012 to October 2015, 81 patients with non-small-cell lung carcinoma (NSCLC), small cell lung carcinoma (SCLC), or esophageal carcinoma where treated with high-dose radio(chemo)therapy...
October 25, 2016: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
Ana Coto-Montes, Jose A Boga, Dun X Tan, Russel J Reiter
Considering the increased speed at which the world population is aging, sarcopenia could become an epidemic in this century. This condition currently has no means of prevention or treatment. Melatonin is a highly effective and ubiquitously acting antioxidant and free radical scavenger that is normally produced in all organisms. This molecule has been implicated in a huge number of biological processes, from anticonvulsant properties in children to protective effects on the lung in chronic obstructive pulmonary disease...
October 24, 2016: International Journal of Molecular Sciences
Julio Jiménez, Jute Richter, Taro Nagatomo, Thomas Salaets, Rozenn Quarck, Allard Wagennar, Hongmei Wang, Jeroen Vanoirbeek, Jan Deprest, Jaan Toelen
Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth...
October 24, 2016: International Journal of Molecular Sciences
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