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Iwao Sugitani, Naoyoshi Onoda, Ken-Ichi Ito, Shinichi Suzuki
Anaplastic thyroid carcinoma (ATC) accounts for only 1 to 2% of all thyroid carcinomas, but it is one of the most lethal neoplasms in humans. To obtain further insights into this "orphan disease," we have established the ATC Research Consortium of Japan (ATCCJ) in 2009. It represents a multicenter registry for ATC that have been treated in Japan. To date, 67 institutions have taken part in the collaborative research system and over 1,200 cases have been accumulated in its database. Using this big data, several retrospective studies were carried out to evaluate 1) prognostic factors to determine initial treatment policy, 2) significance of extended radical surgery for Stage IVB cases, 3) characteristics of ATC incidentally found on pathological examination and 4) pathological features of ATC with long-term survival...
2018: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
Ling Ma, Qiao Cheng
Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid malignancies and resistant to chemotherapy. Little is known on the underlying mechanisms of ATC resistance to chemotherapy. In our work, we identified that 6-phosphogluconate dehydrogenase (6PGD) is critically involved in the development of ATC resistance to doxorubicin. We found that 6PGD mRNA, protein and enzyme activity levels are significantly upregulated in ATC cells during the prolonged exposure to doxorubicin in a time-dependent manner...
March 10, 2018: Biochemical and Biophysical Research Communications
David Ulrich Seidel, Jonas Jae-Hyun Park, Andreas M Sesterhenn, Karel Kostev
AIM: The aim of this study was to analyze the prevalence of dizziness- and vertigo-related diagnoses in ear, nose, and throat (ENT) practices in Germany and the associated demographic characteristics based on data from a representative nationwide practice database. METHOD: The study sample included patients from 138 ENT practices in Germany who received dizziness- and vertigorelated diagnoses (ICD-10 code) between January 2012 and December 2015. Collected parameters included age, sex, insurance status, prescribed medication (anatomical therapeutic chemical [ATC] class), and referrals to other specialists and hospitals...
April 2018: Otology & Neurotology
Jonas W Wastesson, Jaana E Martikainen, Helga Zoëga, Morten Schmidt, Øystein Karlstad, Anton Pottegård
Paracetamol (acetaminophen) is one of the most commonly used analgesics in Europe; however, both the safety and efficacy of paracetamol have recently been questioned. Little is known about cross-national differences in the sales of paracetamol. Using national wholesale statistics and nationwide prescription drug registers, we investigated trends in total and prescribed use of paracetamol in the Nordic countries. The total sales of paracetamol (Anatomical Therapeutic Chemical (ATC) classification system code: N02BE01) measured as defined daily doses (DDD) per 1000 inhabitants/day, and the sales by prescription (users per 1000 inhabitants per year), increased in the Nordic countries from 2000 to 2015...
March 12, 2018: Basic & Clinical Pharmacology & Toxicology
Astha Giri, Shraddha Gupta, Hassan Safi, Anshika Narang, Kamal Shrivastava, Naresh Kumar Sharma, Subramanya Lingaraju, Mahmud Hanif, Anuj Bhatnagar, Balakrishnan Menon, David Alland, Mandira Varma-Basil
Mutations at embB306 are the most prevalent polymorphisms associated with ethambutol (EMB) resistance, responsible for 40-60% of EMB resistant clinical cases of tuberculosis (TB). The present study analyzed additional mutations associated with EMB resistance in the embB, embC, embA and Rv3806c (ubiA) genes in 29 EMB resistant and 29 EMB susceptible clinical isolates of M. tuberculosis selected from 360 patients with TB. The entire ubiA gene, mutational hotspot regions of embB, embC, and upstream region of embA were screened for polymorphisms by DNA sequencing and the results correlated with minimum inhibitory concentrations (MIC) of EMB...
January 2018: Tuberculosis
Shaunak Kar, Andrew D Ellington
T7 RNA polymerase (T7 RNAP) is one of the preferred workhorses for recombinant gene expression, owing in part to its high transcriptional activity and the fact that it has a small (17 base-pair), easily manipulated promoter. Furthermore, the fact that T7 RNAP is largely orthogonal to most hosts enables its use in a wide variety of contexts. However, the high activity of the enzyme also often leads to an increased fitness burden on the host, limiting the predictability of its interactions with and impact on physiology, and potentially leading to mutations to constructs...
March 5, 2018: Methods: a Companion to Methods in Enzymology
Silvia Martina Ferrari, Guido Bocci, Teresa Di Desidero, Ilaria Ruffilli, Giusy Elia, Francesca Ragusa, Anna Fioravanti, Paola Orlandi, Sabrina Rosaria Paparo, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Enke Baldini, Gabriele Materazzi, Paolo Miccoli, Alessandro Antonelli, Poupak Fallahi
The antitumor activity of vandetanib [a multiple signal transduction inhibitor including the RET tyrosine kinase, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor (VEGFR), ERK and with antiangiogenic activity], in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C [undifferentiated thyroid cancer (TC)] and in an ATC‑cell line (AF), was investigated in the present study. Vandetanib (1 and 100 nM; 1, 10, 25 and 50 µM) was tested by WST‑1, apoptosis, migration and invasion assays: in primary ATC cells, in the 8305C continuous cell line, and in AF cells; and in 8305C cells in CD nu/nu mice...
March 8, 2018: Oncology Reports
Silvia Martina Ferrari, Guido Bocci, Teresa Di Desidero, Giusy Elia, Ilaria Ruffilli, Francesca Ragusa, Paola Orlandi, Sabrina Rosaria Paparo, Armando Patrizio, Simona Piaggi, Concettina La Motta, Salvatore Ulisse, Enke Baldini, Gabriele Materazzi, Paolo Miccoli, Alessandro Antonelli, Poupak Fallahi
Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor (TKI) of VEGFR1-VEGFR3, FGFR1-FGFR4, PDGFRα, RET and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks involved in tumor angiogenesis. We have evaluated the antitumor activity of lenvatinib in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer) and in an ATC-cell line (AF). The AF cell line was obtained from the primary ATC cultures and was the one that grew over 50 passages...
March 8, 2018: Oncology Reports
Jing Liu, Liguo Feng, Haitao Zhang, Jin Zhang, Yanyan Zhang, Shujing Li, Long Qin, Ziyao Yang, Jianxia Xiong
BACKGROUND: We investigated the influence of miR-144 on the cisplatin-sensitivity of anaplastic thyroid carcinoma (ATC) cells and explored the internal molecular mechanism of miR-144. RESULTS: MiR-144, which was low expressed in ATC cells and tissues, could inhibit autophagy activation induced by cisplatin, enhancing the sensitivity of ATC cells to cisplatin, and promoting cell apoptosis. TGF-α was the target of miR-144 and was negatively regulated by it. MiR-144 could improve the sensitivity of ATC cells to cisplatin and inhibit tumor growth by suppressing TGF-α both in vitro and in vivo...
March 5, 2018: Cancer Biology & Therapy
Siling Zhao, Neal Mankad
We have developed a reductive carbonylation method by which unactivated alkyl iodides can be hydroxymethylated to provide one carbon extended alcohol products under Cu-catalyzed conditions. The method is tolerant of alkyl beta-hydrogens, is robust towards a wide variety of functional groups, and has been applied to primary, secondary, and tertiary alkyl iodide substrates. Mechanistic experiments indicate that the transformation proceeds by atom transfer carbonylation (ATC) of the alkyl iodide followed in tandem by two CuH-mediated reductions in rapid succession...
March 5, 2018: Angewandte Chemie
Ehsan Akbari, Saeed Safari, Hamidreza Hatamabadi
INTRODUCTION: The debate on replacing coagulation factors and its effect on the final outcome of the patients with acute traumatic coagulopathy (ATC) in need of transfusion is still ongoing. Therefore, the present study is designed with the aim of comparing the outcome of patients with acute traumatic coagulopathies receiving fibrinogen and fresh frozen plasma (FFP). METHODS: In this quasi-experimental randomized controlled study, patients with severe blunt trauma (ISS>16) and in need of packed cells transfusion were divided into 3 groups of receiving fibrinogen, receiving FFP, and control, and their final outcome was compared...
February 22, 2018: American Journal of Emergency Medicine
Charlotte Rouzaud-Laborde, Pierre Lafitte, Laurent Balardy, Zofia Czosnyka, Eric A Schmidt
OBJECTIVES:  Arterial hypertension is among the leading risks for mortality. This burden requires in hypertensive patients the use of single, double or more antihypertensive drugs. The relationship between intracranial pressure (ICP) and arterial blood pressure is complex and still under debate. The impact of antihypertensive drugs on ICP is unknown. We wanted to understand whether the use of antihypertensive drugs has a significant influence on ICP and cerebrospinal fluid (CSF)/brain related parameters...
2018: Acta Neurochirurgica. Supplement
F M Garritsen, J M van den Heuvel, C A F M Bruijnzeel-Koomen, A H Maitland-van der Zee, M P H van den Broek, M S de Bruin-Weller
BACKGROUND: Although atopic dermatitis (AD) is a very common skin disease, data on the percentage of patients with really difficult to treat AD are scarce. From socio-economic perspective it is important to have more insight in these numbers, as new very effective, but expensive, treatment options will be available in the near future for difficult to treat AD. Estimating the number of AD patients using oral immunosuppressive drugs can give an impression of the percentage of difficult to treat patients in the total AD population...
February 27, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Naris Nilubol, ZiQiang Yuan, Giulio F Paciotti, Lawrence Tamarkin, Carmen Sanchez, Kelli Gaskins, Esther M Freedman, Shugeng Cao, Jielu Zhao, David G I Kingston, Steven K Libutti, Electron Kebebew
Background: The advantages of nanomedicines include preferential delivery of the payload directly to tumor tissues. CYT-21625 is the novel, first-in-class gold nanomedicine designed to target tumor vasculature and cancer cells by specifically delivering recombinant human tumor necrosis factor alpha (rhTNF) and a paclitaxel prodrug. Methods: We analyzed TNF receptor expression in publicly available gene expression profiling data and in thyroid tissue samples. Mice with metastatic FTC-133 and 8505C xenografts and the MEN1 conditional knock-out mice were treated weekly with CYT-21625 and gold nanoparticles with rhTNF only (CYT-6091); controls included mice treated with either paclitaxel or saline...
February 22, 2018: Journal of the National Cancer Institute
Ji Min Oh, Senthilkumar Kalimuthu, Prakash Gangadaran, Se Hwan Baek, Liya Zhu, Ho Won Lee, Ramya Lakshmi Rajendran, Chae Moon Hong, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
Radioactive-iodine (RAI) therapy is typically unprevailing as anaplastic thyroid cancer (ATC) management, owing to the decrease in the endogenous sodium iodide symporter (NIS) expression. Therefore, new strategies for NIS re-induction are required to improve the efficacy of RAI therapy in ATC. In this study, we developed a novel high-throughput NIS enhancer screening platform using a dual reporter gene system to identify a potent tyrosine kinase inhibitor (TKI) and selected a new hit compound, K905-0266 TKI...
January 23, 2018: Oncotarget
Sabine Vogler, Roger H P F de Rooij
BACKGROUND: Despite potentially considerable implications for public health, the environment and public funds, medicine waste is an under-researched topic. This study aims to analyse medicines drawn from household garbage in Vienna (Austria) and to assess possible financial implications for public payers. METHODS: Four pharmaceutical waste samples collected by the Vienna Municipal Waste Department between April 2015 and January 2016 were investigated with regard to their content...
February 10, 2018: Research in Social & Administrative Pharmacy: RSAP
Nathalie Ferreira Silva de Melo, Estefânia Vangelie Ramos Campos, Michelle Franz-Montan, Eneida de Paula, Camila Morais Gonçalves da Silva, Cíntia Rodrigues Maruyama, Tatiane Pasquoto Stigliani, Renata de Lima, Daniele Ribeiro de Araújo, Leonardo Fernandes Fraceto
This work describes the development of poly-ε-caprolactone nanocapsules (PCL-NC) and solid lipid nanoparticles (SLN) aiming delivery for articaine (ATC), in order to improve its chemical stability in semi-solid preparations looking forward their use for skin delivery. The nanoparticles were characterized by size, polydispersity index, and pH. Cellular viability was evaluated using the MTT test and the in vitro release kinetics was determined using a two-compartment model. The hydrogels with nanoparticle suspensions were characterized considering their rheological aspects and in vitro permeation across artificial membranes...
June 1, 2018: Journal of Nanoscience and Nanotechnology
Jürgen Stein, Jennifer Scarlet Haas, Siew Hwa Ong, Kathrin Borchert, Thomas Hardt, Elmira Lechat, Kerry Nip, Douglas Foerster, Sebastian Braun, Daniel C Baumgart
Background: Iron-deficiency anemia and iron deficiency are common comorbidities associated with inflammatory bowel disease (IBD) resulting in impaired quality of life and high health care costs. Intravenous iron has shown clinical benefit compared to oral iron therapy. Aim: This study aimed to compare health care outcomes and costs after oral vs intravenous iron treatment for IBD patients with iron deficiency or iron deficiency anemia (ID/A) in Germany. Methods: IBD patients with ID/A were identified by ICD-10-GM codes and newly commenced iron treatment via ATC codes in 2013 within the InGef (formerly Health Risk Institute) research claims database...
2018: ClinicoEconomics and Outcomes Research: CEOR
Ewelina Motylewska, Tomasz Stępień, Magdalena Borkowska, Krzysztof Kuzdak, Agnieszka Siejka, Jan Komorowski, Henryk Stępień, Hanna Ławnicka
INTRODUCTION: βKlotho (βKL) is known to act as co-receptor for fibroblast growth factor receptor 4 (FGFR4) which is the main cognate receptor for fibroblast growth factor 19 (FGF19). Dysregulation of this FGF19/FGFR4/βKL signaling axis has been implicated in the pathogenesis of several cancers. However, its role in the pathogenesis of thyroid cancer has not been determined. MATERIALS AND METHODS: The aim of this study was to assess FGF19, FGFR4 and βKL concentrations in a group of 36 patients with papillary thyroid cancer (PTC), 11 patients with follicular thyroid cancer (FTC), 9 patients with anaplastic thyroid cancer (ATC) and a group of 19 subjects with multinodular nontoxic goiter (MNG)...
February 10, 2018: Cytokine
Alessia Parascandolo, Mikko O Laukkanen, Nancy De Rosa, Clara Ugolini, Maria Carmela Cantisani, Anna Maria Cirafici, Fulvio Basolo, Massimo Santoro, Maria Domenica Castellone
Sonic Hedgehog (Shh) pathway regulates embryonic development of different organs including the thyroid gland. The aberrant activation of Shh signaling has been found in several types of cancer and according to recent evidences it represents an important regulator of tumor-stroma interaction. In this study, we have analyzed expression, activation and molecular mechanisms regulating the Shh pathway and its involvement in the modulation of tumor stroma interaction in anaplastic thyroid cancer (ATC) cells. Our results suggest that Shh signaling undergoes a dual mechanism of induction in ATC cells: 1) a basal non-canonical Smo-dependent activation of Gli transcription factor that is partly caused by interaction with the RAS/BRAF/MEK oncogenic pathway and is characterized by the absence of Shh ligand expression in thyroid cancer cells and 2) a paracrine response of cancer cells to Shh ligand secreted by tumor stroma (fibroblasts and mesenchymal stromal cells, MSCs) inducing cancer cell migration and in vitro tumorigenesis...
January 12, 2018: Oncotarget
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