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Zhi-Xin Qiu, Yue Cheng, Dan Liu, Wei-Ya Wang, Xia Wu, Wei-Lu Wu, Wei-Min Li
BACKGROUND: Lung nodules are being detected at an increasing rate year by year with high-resolution computed tomography (HRCT) being widely used. Ground-glass opacity nodule is one of the special types of pulmonary nodules that is confirmed to be closely associated with early stage of lung cancer. Very little is known about solitary ground-glass opacity nodules (SGGNs). In this study, we analyzed the clinical, pathological, and radiological characteristics of SGGNs on HRCT. METHODS: A total of 95 resected SGGNs were evaluated with HRCT scan...
2016: Therapeutics and Clinical Risk Management
Disha Pathak, Navriti Chadha, Om Silakari
Proto-oncogene receptor tyrosine kinase ROS-1 plays a key role in regulating a variety of cancers mainly non-small cell lung cancer (NSCLC). The marketed ROS-1 inhibitors such as Crizotinib suffer from the tribulations of growing resistance due to mutations primarily Gly2032Arg in the ROS-1 protein. To curb the problem of resistance, researchers have developed inhibitors such as Lorlatinib against the mutant protein. The present study was designed to identify inhibitors against wild type (WT) as well as mutant ROS-1 protein that will offer a broader spectrum of activity...
September 29, 2016: Journal of Molecular Graphics & Modelling
Esther Camp, Peter J Anderson, Andrew C W Zannettino, Stan Gronthos
The TWIST-1 gene encodes a basic helix-loop-helix (bHLH) transcription factor important in mediating skeletal and head mesodermal tissue development. Bone marrow-derived mesenchymal stem/ stromal cells (BMSC), express high levels of TWIST-1, which is down regulated during ex vivo expansion. Cultured BMSC over-expressing TWIST-1 display decreased capacity for osteogenic differentiation and an enhanced capacity to undergo adipogenesis, suggesting that TWIST-1 is a mediator of lineage commitment. However, little is known regarding the mechanism(s) by which TWIST-1 mediates cell fate determination...
September 23, 2016: Bone
Eduardo A Rodriguez, Elie Donath, Akbar K Waljee, Daniel A Sussman
BACKGROUND: Intravenous (IV) proton pump inhibitors (PPI) are the standard medical treatment in acute nonvariceal upper gastrointestinal bleeding (ANVGIB). Optimal route of PPI delivery has been questioned. AIM: The aim was to perform a systematic review and network meta-analysis for the endpoints of risk of rebleeding, length of stay (LOS), surgery (ROS), mortality, and total units of blood transfused (UBT) among trials evaluating acid suppressive medications in ANVGIB...
August 8, 2016: Journal of Clinical Gastroenterology
Caroline E McCoach, Trever G Bivona, Collin M Blakely, Robert C Doebele
Evaluations of resistance mechanisms to targeted treatments in non-small-cell lung cancer (NSCLC) are necessary for development of improved treatment after disease progression and to help delay progression of disease. Populations of cells that survive after initial treatment form the basis of resistance via outgrowth of resistant clones or activation of alternative signaling pathways. In this report we describe a clinical trial approach in which patients with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), C-ros-1 proto-oncogene (ROS1), and hepatocyte growth factor receptor (MET) exon 14 alterations and early stage (IA-IIIA) NSCLC will be treated with induction EGFR tyrosine kinase inhibitor (TKI) or crizotinib, a TKI that inhibits ALK, ROS1, and MET...
June 8, 2016: Clinical Lung Cancer
Magdalena Ostafin, Michal Przemyslaw Pruchniak, Olga Ciepiela, Abraham Zeev Reznick, Urszula Demkow
A unique strategy, in which invading microorganisms are being caught in web-like structures composed mainly of DNA, involves a recently described phenomenon called NETosis. This process seems to be related to the production of reactive oxygen species (ROS). In our study, the influence of diphenyleneiodonium chloride (DPI), which diminishes ROS production, was assessed in the context of neutrophil extracellular trap (NET) release. According to protocol, two distinguished procedures were compared, the first one involving DPI elimination from sample before cell activation and the second one proceeding without the step of inhibitor washout...
September 15, 2016: Analytical Biochemistry
Horacio Figueroa, Jorge Cifuentes, Mauricio Lozano, Cristobal Alvarado, Claudia Cabezas, Elisenda Eixarch, Ellio Fernández, Luis Contreras, Sebastian E Illanes, Edgar Hernández-Andrade, Eduard Gratacós, Carlos E Irarrazabal
OBJECTIVE: This work aimed to study the effect of uteroplacental circulation restriction on endothelial kidney damage in a fetal rabbit model. METHODS: New Zealand rabbits were subjected to 40% to 50% of uteroplacental artery ligation at day 25 of pregnancy. After 5 days, surviving fetuses were harvested by cesarean section. The gene and protein expressions of selected enzymes associated with nitric oxide production and oxidative stress were analyzed in fetal kidney homogenates...
July 2016: Prenatal Diagnosis
Larisa Pereboeva, Meredith Hubbard, Frederick D Goldman, Erik R Westin
Dyskeratosis Congenita (DC) is an inherited multisystem premature aging disorder with characteristic skin and mucosal findings as well as a predisposition to cancer and bone marrow failure. DC arises due to gene mutations associated with the telomerase complex or telomere maintenance, resulting in critically shortened telomeres. The pathogenesis of DC, as well as several congenital bone marrow failure (BMF) syndromes, converges on the DNA damage response (DDR) pathway and subsequent elevation of reactive oxygen species (ROS)...
2016: PloS One
Peijie He, Wenjing Mao, Huankang Zhang, Liang Zhou
OBJECTIVE: To investigate the effect and potential mechanisms about apoptosis induction and migration suppression of photodynamic therapy with a new photosensitizer, 9-hydroxypheophorbide-α (9-HPbD), and diode laser on HN-3 human laryngeal squamous cancer cells. METHOD: The attached HN-3 cancer cells were photosesitized with 0.29 μg/ml and 0.59 μg/ml 9-HPbD for 6 h and irradiated by 664 nm diode laser for 15 min at an energy density of 2.0 J/cm for activating 9-HPbD...
August 2015: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
J Kurtz, B Rael, J Lerma, C Wright, T Khraishi, E D Auyang
BACKGROUND: Oxidative degradation by reactive oxygen species (ROS) from inflammation initiates cross-linking, depolymerization, and formation of a quasi-crystalline quality in polypropylene (PP) meshes that cause embrittlement (J Urol 188:1052, 2012). Embrittlement leads to change in tensile strength and is associated with post-operative complications that include pain, adhesion, dislodgment, and fragmentation. METHODS: A laboratory environment was constructed to study the relationship between concentration of ROS and change in tensile strength...
August 2016: Surgical Endoscopy
Charles B Simone, Stuart H Burri, John H Heinzerling
Targeted therapies and immunotherapies have quickly become fixtures in the treatment armamentarium for metastatic non-small cell lung cancer (NSCLC). Targeted therapies directed against epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) translocations, and ROS-1 rearrangements have demonstrated improved progression free survival (PFS) and, in selected populations, improved overall survival (OS) compared with cytotoxic chemotherapy. Immunotherapies, including checkpoint inhibitor monoclonal antibodies against programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1), have now also demonstrated improved survival compared with chemotherapy...
October 2015: Translational Lung Cancer Research
Zhixian Zhang, Feng He, Ryan Constantine, Matthew L Baker, Wolfgang Baehr, Michael F Schmid, Theodore G Wensel, Melina A Agosto
The cGMP phosphodiesterase of rod photoreceptor cells, PDE6, is the key effector enzyme in phototransduction. Two large catalytic subunits, PDE6α and -β, each contain one catalytic domain and two non-catalytic GAF domains, whereas two small inhibitory PDE6γ subunits allow tight regulation by the G protein transducin. The structure of holo-PDE6 in complex with the ROS-1 antibody Fab fragment was determined by cryo-electron microscopy. The ∼11 Å map revealed previously unseen features of PDE6, and each domain was readily fit with high resolution structures...
May 15, 2015: Journal of Biological Chemistry
Thomas A Melnik, Cemile G Guldal, Lawrence D Schoen, Jeanne Alicandro, Paul Henfield
Birth records have important legal, administrative and public health uses. However, invalid and incomplete birth reporting is a significant problem in New York State (NYS) and nationwide. We aimed to identify current practices and potential barriers in data collection by birth registrars (BRs) in NYS facilities. Using a 28-question survey regarding birth data collection, we surveyed 127 BRs in August 2013. The response rate was 88.2% (n = 112), with 31.2% from New York City (NYC) and 68.8% from the Rest of State (ROS)...
September 2015: Maternal and Child Health Journal
Yuanyuan Zhang, Lirong Han, Wentao Qi, Dai Cheng, Xiaolei Ma, Lihua Hou, Xiaohong Cao, Chunling Wang
Eicosapentaenoic acid (EPA), a well-known dietary n-3 PUFAS, has been considered to inhibit proliferation of tumor cells. However, the molecular mechanism related to EPA-induced liver cancer cells apoptosis has not been reported. In this study, we investigated the effect of EPA on HepG2 cells proliferation and apoptosis mechanism through mitochondrial pathways. EPA inhibited proliferation of HepG2 cells in a dose-dependent manner and had no significant effect on the cell viability of humor normal liver L-02 cells...
January 24, 2015: Biochemical and Biophysical Research Communications
Na Zhang, Jin-Ji Yang, Xu-Chao Zhang, Zhi Xie, Bin-Chao Wang, Hai-Yan Tu, Ben-Yuan Jiang, Yi-Long Wu
Rearrangements to the c-ros oncogene 1, receptor tyrosine kinase (ROS1) gene are reported in 1-2% of lung adenocarcinomas. These rearrangements are associated with a response to the small-molecule tyrosine kinase inhibitor crizotinib. ROS1 rearrangements can be detected using fluorescence in situ hybridization (FISH), which is considered the gold standard technique in detecting ROS1 rearrangements, and determining whether a patient would respond well to crizotinib treatment. However, FISH is an expensive and time-consuming assay, requiring specialized microscopy equipment and some level of technical expertise...
December 2014: Oncology Letters
Grzegorz J Korpanty, Donna M Graham, Mark D Vincent, Natasha B Leighl
Lung cancer remains the most lethal malignancy in the world. Despite improvements in surgical treatment, systemic therapy, and radiotherapy, the 5-year survival rate for all patients diagnosed with lung cancer remains between 15 and 20%. Newer therapeutic strategies rely on specific molecular alterations, or biomarkers, that provide opportunities for a personalized approach to specific patient populations. Classification of lung cancer is becoming increasingly focused on these biomarkers, which renders the term "non-small cell lung" cancer less clinically useful...
2014: Frontiers in Oncology
Anna M Leung, Maria J Redlak, Thomas A Miller
BACKGROUND: The generation of reactive oxygen species (ROS) and their resultant oxidative damage is a common pathway for gastric mucosal injury. Developing strategies to protect the gastric epithelium against oxygen free radical damage is of profound pathophysiological interest. We have previously shown caspase-mediated apoptosis as a major cause of ROS-induced cell death in gastric mucosa. Because heat shock proteins (Hsps) confer protection against many cytotoxic agents, this study was undertaken to determine whether modulation of Hsps was protective against oxidative damage...
January 2015: Journal of Surgical Research
Meike Schneider, Julia Schüler, Rouven Höfflin, Nina Korzeniewski, Carsten Grüllich, Wilfried Roth, Dogu Teber, Boris Hadaschik, Sascha Pahernik, Markus Hohenfellner, Stefan Duensing
OBJECTIVES: Novel personalized therapeutic approaches are urgently needed for patients with metastatic clear cell renal cell carcinoma (ccRCC). METHODS AND MATERIALS: We combined the development of a primary patient-derived ccRCC cell line with a phenotypic drug screen consisting of 101 approved anticancer compounds. RESULTS: We identified the MNNG HOS transforming gene (MET)-anaplastic lymphoma receptor tyrosine kinase (ALK) inhibitor crizotinib as the top hit of our drug screen, whereas compounds targeting the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway showed no or only minor in vitro activity...
August 2014: Urologic Oncology
Moshi Song, Yun Chen, Guohua Gong, Elizabeth Murphy, Peter S Rabinovitch, Gerald W Dorn
RATIONALE: Mitochondrial reactive oxygen species (ROS) are implicated in aging, chronic degenerative neurological syndromes, and myopathies. On the basis of free radical hypothesis, dietary, pharmacological, and genetic ROS suppression has been tested to minimize tissue damage, with remarkable therapeutic efficacy. The effects of mitochondrial-specific ROS suppression in primary mitophagic dysfunction are unknown. OBJECTIVE: An in vivo dose-ranging analysis of ROS suppression in an experimental cardiomyopathy provoked by defective mitochondrial clearance...
July 18, 2014: Circulation Research
Barbara Iovine, Giorgia Oliviero, Mariangela Garofalo, Maria Orefice, Francesca Nocella, Nicola Borbone, Vincenzo Piccialli, Roberto Centore, Massimiliano Mazzone, Gennaro Piccialli, Maria Assunta Bevilacqua
In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS) production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α) as a possible target of L-carnosine in HCT-116 cell line...
2014: PloS One
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