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https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#1
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of non-small cell lung cancer (NSCLC) underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival (OS) both in unselected pretreated patients and in untreated patients with PD-L1 expression ≥50%. Furthermore, compelling preliminary results were reported for new combinations of anti-PD-1/PD-L1 agents with chemotherapy or anti-CTLA4 inhibitors. The success of the ICIs appeared to extend to patients with small cell lung cancer (SCLC), mesothelioma or thymic tumors...
January 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29326158/reciprocal-spatiotemporally-controlled-apoptosis-regulates-wolffian-duct-cloaca-fusion
#2
Masato Hoshi, Antoine Reginensi, Matthew S Joens, James A J Fitzpatrick, Helen McNeill, Sanjay Jain
The epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder) before metanephric kidney development, thereby establishing the initial plumbing for eventual joining of the ureters and bladder. Defects in this process cause common anomalies in the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). However, developmental, cellular, and molecular mechanisms of WD-cloaca fusion are poorly understood. Through systematic analysis of early WD tip development in mice, we discovered that a novel process of spatiotemporally regulated apoptosis in WD and cloaca was necessary for WD-cloaca fusion...
January 11, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29324283/a-novel-electrochemiluminescent-biosensor-based-on-resonance-energy-transfer-between-poly-9-9-di-n-octylfluorenyl-2-7-diyl-and-3-4-9-10-perylenetetracar-boxylic-acid-for-insulin-detection
#3
Han Zhang, Fumei Zuo, Xingrong Tan, Shenghao Xu, Ruo Yuan, Shihong Chen
An electrochemiluminescencent (ECL) biosensor was designed for the determination of insulin using a novel ECL resonance energy transfer (ECL-RET) strategy. In this strategy, carboxyl poly(9,9-dioctyfluorenyl-2,7-diyl) dots (PFO dots) were worked as ECL donor and 3,4,9,10-perylenetetracar-boxylic acid (PTCA) exploited as ECL acceptor, and hydrogen peroxide (H2O2) employed as the coreactant. The ECL donor and ECL acceptor were separately labeled with primary antibody (Ab1) and secondary antibody (Ab2), forming a sensing interface to the analyte target, insulin...
December 27, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29323915/resonance-energy-transfer-promoted-photothermal-and-photodynamic-performance-of-gold-copper-sulfide-yolk-shell-nanoparticles-for-chemophototherapy-of-cancer
#4
Yun Chang, Yan Cheng, Yanlin Feng, Hui Jian, Li Wang, Xiaomin Ma, Xi Li, Haiyuan Zhang
Gold (Au) core@void@copper sulfide (CuS) shell (Au-CuS) yolk-shell nanoparticles (YSNPs) were prepared in the present study for potential chemo-, photothermal, and photodynamic combination therapy, so called "chemophototherapy". The resonance energy transfer (RET) process was utilized in Au-CuS YSNPs to achieve both enhanced photothermal and photodynamic performance compared with those of CuS hollow nanoparticles (HNPs). A series of Au nanomaterials as cores that had different localized surface plasmon resonance (LSPR) absorption peaks at 520, 700, 808, 860, and 980 nm were embedded in CuS HNPs to screen the most effective Au-CuS YSNPs according to the RET process...
January 11, 2018: Nano Letters
https://www.readbyqxmd.com/read/29323497/multi-funnel-landscape-of-the-fold-switching-protein-rfah-ctd
#5
Nathan A Bernhardt, Ulrich H E Hansmann
Proteins such as the transcription factor RfaH can change biological function by switching between distinct three-dimensional folds. RfaH regulates transcription if the C-terminal domain folds into a double helix bundle, and promotes translation when this domain assumes a β-barrel form. This fold-switch has been also observed for the isolated domain, dubbed by us RfaH-CTD, and is studied here with a variant of the RET approach recently introduced by us. We use the enhanced sampling properties of this technique to map the free energy landscape of RfaH-CTD and to propose a mechanism for the conversion process...
January 11, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29321660/activated-alk-signals-through-the-erk-etv5-ret-pathway-to-drive-neuroblastoma-oncogenesis
#6
Lucille Lopez-Delisle, Cécile Pierre-Eugène, Caroline Louis-Brennetot, Didier Surdez, Virginie Raynal, Sylvain Baulande, Valentina Boeva, Sandrine Grossetête-Lalami, Valérie Combaret, Michel Peuchmaur, Olivier Delattre, Isabelle Janoueix-Lerosey
Activating mutations of the ALK receptor occur in a subset of neuroblastoma tumors. We previously demonstrated that Alk mutations cooperate with MYCN overexpression to induce neuroblastoma in mice and identified Ret as being strongly upregulated in MYCN/Alkmut tumors. By a genetic approach in vivo, we now document an oncogenic cooperation between activated Ret and MYCN overexpression in neuroblastoma formation. We show that MYCN/RetM919T tumors exhibit histological features and expression profiles close to MYCN/Alkmut tumors...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29319359/secondary-and-tertiary-preventions-of-thyroid-disease
#7
Fereidoun Azizi, Ladan Mehran, Farhad Hosseinpanah, Hossein Delshad, Atieh Amouzegar
INTRODUCTION: Secondary and tertiary preventions are concerned with the recognition of the disease process in a very early stage and delay in progression to complete disease and minimization of complications and the impact of illness. METHODS: All articles related to secondary and tertiary prevention of thyroid diseases were reviewed. Using related key words, articles published between 2001 and 2015 were evaluated, categorized, and analyzed. RESULTS: In secondary prevention, congenital hypothyroidism and subclinical hypo and hyperthyroidism are equally important...
January 10, 2018: Endocrine Research
https://www.readbyqxmd.com/read/29317515/intratumoural-heterogeneity-may-hinder-precision-medicine-strategies-in-patients-with-clear-cell-renal-cell-carcinoma
#8
Maria Rosaria Raspollini, Ilaria Montagnani, Rodolfo Montironi, Francesca Castiglione, Guido Martignoni, Liang Cheng, Antonio Lopez-Beltran
Clear cell renal cell carcinoma (ccRCC) is an heterogeneous tumour at architectural, cellular and molecular level, a reason why the 2014 International Society of Urological Pathology consensus recommended wide sampling of RCC masses to include at least 1 block/cm of tumour together with perpendicular sections of the tumour/perinephric fat interface and the tumour/renal sinus interface. Intratumoural molecular heterogeneity may be a limitation at the moment of defining precision medicine strategies based on gene mutation status...
January 9, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29316748/-preliminary-study-of-exon-sequence-in-pneumoconiosis-and-pneumoconiosis-complicated-with-lung-cancer-using-high-throughput-sequencing-technology
#9
M F Jiang, L Li, Z Wang, C L Zhang, H Zhang
Objective: The detection and analysis of exon mutations of pneumoconiosis and pneumoco-niosis complicated with lung cancer provide reference evidence for screening, clinical diagnosis and treatment and prognosis in pneumoconiosis and pneumoconiosis complicated with lung cancer. Methods: The pathologi-cal tissue samples from 3 pneumoconiosis patients and 3 pneumoconiosis complicated with lung cancer pa-tients were collected. Genomic DNA was extracted and library was prepared. Exomes of the pathological tissue samples in pneumoconiosis patients and pneumoconiosis complicated with lung cancer patients were se-quenced using Ion Torrent PGM platform...
November 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/29312631/proteomic-approach-toward-determining-the-molecular-background-of-pazopanib-resistance-in-synovial-sarcoma
#10
Zhiwei Qiao, Kumiko Shiozawa, Tadashi Kondo
Pazopanib, a multitarget tyrosine kinase (TK) inhibitor, has been approved for treatment of soft tissue sarcoma. Elucidation of the molecular background of pazopanib resistance should lead to improved clinical outcomes in sarcomas; accordingly, we investigated this in synovial sarcoma using a proteomic approach. Pazopanib sensitivity was examined in four synovial sarcoma cell lines: SYO-1, HS-SYII, 1273/99, and YaFuSS. The 1273/99 cell line showed significantly higher IC50 values than the others for pazopanib...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29312610/inhibitor-repurposing-reveals-alk-ltk-fgfr-ret-and-trk-kinases-as-the-targets-of-azd1480
#11
Iva Gudernova, Lukas Balek, Miroslav Varecha, Jana Fialova Kucerova, Michaela Kunova Bosakova, Bohumil Fafilek, Veronika Palusova, Stjepan Uldrijan, Lukas Trantirek, Pavel Krejci
Many tyrosine kinase inhibitors (TKIs) have failed to reach human use due to insufficient activity in clinical trials. However, the failed TKIs may still benefit patients if their other kinase targets are identified by providing treatment focused on syndromes driven by these kinases. Here, we searched for novel targets of AZD1480, an inhibitor of JAK2 kinase that recently failed phase two cancer clinical trials due to a lack of activity. Twenty seven human receptor tyrosine kinases (RTKs) and 153 of their disease-associated mutants were in-cell profiled for activity in the presence of AZD1480 using a newly developed RTK plasmid library...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29306055/trimethoprim-sulfamethoxazole-treatment-increases-the-pig-a-mutant-frequency-in-peripheral-blood-from-severely-malnourished-rats
#12
M Monserrat Pacheco-Martínez, Elsa Cervantes-Ríos, María Del Carmen García-Rodríguez, Rocío Ortiz-Muñiz
Severe malnutrition is a complex condition that increases susceptibility to infections. Thus, drugs are extensively used in malnutrition cases. In the present study, we assessed the mutagenic effects of combined trimethoprim and sulfamethoxazole (TMP-SMX) treatment in undernourished (UN) and well-nourished (WN) rats. Six-week-old UN and WN Han-Wistar rats were treated with TMP-SMX at a daily dose of 10 mg/kg/d TMP and 50 mg/kg/d SMX for 5 or 10 days. Blood was collected from the tail vein one day before (day -1) and 15, 30, and 45 days after TMP-SMX administration...
December 30, 2017: Mutation Research
https://www.readbyqxmd.com/read/29303187/-where-does-the-fluorescing-moiety-reside-in-a-carbon-dot-investigations-based-on-fluorescence-anisotropy-decay-and-resonance-energy-transfer-dynamics
#13
Ananya Das, Debjit Roy, Chayan K De, Prasun K Mandal
It has been shown recently that aggregated dyes are responsible for very high fluorescence in a carbon dot (CD). However, what is the location of the fluorescing moiety in CD? Is it inside the CD or attached to the CD's surface? In order to answer these intriguing questions regarding the location of the fluorescing moiety in a CD, we performed rotational anisotropy decay dynamics and resonance energy transfer (RET) dynamics. Rotational correlation time of ∼120 picoseconds nullifies the fact that the whole CD is fluorescing...
January 5, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29290262/gcc2-alk-as-a-targetable-fusion-in-lung-adenocarcinoma-and-its-enduring-clinical-responses-to-alk-inhibitors
#14
Junhong Jiang, Xue Wu, Xiaoling Tong, Wangzhi Wei, Anan Chen, Xiaonan Wang, Yang W Shao, Jianan Huang
OBJECTIVES: ALK, RET and ROS1 fusions have been identified as treatable targets in 5%-15% of non-small-cell lung cancers, and thanks to the advanced sequencing technologies, their new partner genes have been steadily detected. Here we identified a rare fusion of ALK (GCC2-ALK) in a patient with advanced lung adenocarcinoma and monitored the treatment efficacy of ALK inhibitors on this patient. We further performed in vitro functional studies of this fusion protein for evaluating its oncogenic potential...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29287802/acute-and-sub-chronic-toxicological-studies-of-the-iridoid-glycosides-extract-of-lamiophlomis-rotata-benth-kudo-in-rats
#15
Quanlong Zhang, Zhujun Mao, Qiaoyan Zhang, Jianguo Qiu, Zhengping Jia, Luping Qin
Lamiophlomis rotata(Benth.) Kudo is widely used in traditional Chinese medicine and its iridoid glycosides extract (IGLR) was the main active ingredient with hemostatic, antinociceptive and anti-inflammatory effects. This study was aimed to evaluate the safety of IGLR using acute and sub-chronic toxicity study methods on Sprague-Dawley rats. In acute toxicity test, IGLR caused slight diarrhea in three dose groups and a decreased of RBC and increased of MCH and Ret (P < .05) were observed in 16 g/kg group...
December 26, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29287240/label-free-impedimetric-glycan-biosensor-for-quantitative-evaluation-interactions-between-pathogenic-bacteria-and-mannose
#16
Feiyun Cui, Yi Xu, Renjie Wang, Haitao Liu, Li Chen, Qing Zhang, Xiaojing Mu
In order to understanding the pathogenic mechanism of infectious diseases, it was important to study the selective recognition and interaction between pathogenic bacteria and host cells. In this paper, a novel electrochemical impedance biosensor was proposed, in which the Man/MUA-MH/Au sensing surface (Man: mannose; MUA: 11-mercapto eleven acid; MH: 6-mercapto hexanol) was fabricated and was of good biologically active and stability. The capture capacity of the designed sensing surface for S. typhimurium ATCC14028, E...
December 2, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29284153/role-of-ret-protein-tyrosine-kinase-inhibitors-in-the-treatment-ret-driven-thyroid-and-lung-cancers
#17
REVIEW
Robert Roskoski, Abdollah Sadeghi-Nejad
RET is a transmembrane receptor protein-tyrosine kinase that is required for the development of the nervous system and several other tissues. The mechanism of activation of RET by its glial-cell derived neurotrophic factor (GDNF) ligands differs from that of all other receptor protein-tyrosine kinases owing to the requirement for additional GDNF family receptor-α (GFRα) co-receptors (GFRα1/2/3/4). RET point mutations have been reported in multiple endocrine neoplasia (MEN2A, MEN2B) and medullary thyroid carcinoma...
December 25, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29282324/biphasic-functions-for-the-gdnf-ret-signaling-pathway-in-chemosensory-neuron-development-and-diversification
#18
Christopher R Donnelly, Amol A Shah, Charlotte M Mistretta, Robert M Bradley, Brian A Pierchala
The development of the taste system relies on the coordinated regulation of cues that direct the simultaneous development of both peripheral taste organs and innervating sensory ganglia, but the underlying mechanisms remain poorly understood. In this study, we describe a novel, biphasic function for glial cell line-derived neurotrophic factor (GDNF) in the development and subsequent diversification of chemosensory neurons within the geniculate ganglion (GG). GDNF, acting through the receptor tyrosine kinase Ret, regulates the expression of the chemosensory fate determinant Phox2b early in GG development...
December 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29261189/ret-somatic-mutations-are-underrecognized-in-hirschsprung-disease
#19
Qian Jiang, Fang Liu, Chunyue Miao, Qi Li, Zhen Zhang, Ping Xiao, Lin Su, Kaihui Yu, Xiaoli Chen, Feng Zhang, Aravinda Chakravarti, Long Li
PurposeWe aimed to determine the frequency of RET mosaicism in Hirschsprung disease (HSCR), test whether it has been underestimated, and to assess its contribution to HSCR risk.MethodsTargeted exome sequencing (n = 83) and RET single-gene screening (n = 69) were performed. Amplicon-based deep sequencing was applied on multiple tissue samples. TA cloning and sequencing were conducted for validation.ResultsWe identified eight de novo mutations in 152 patients (5.2%), of which six were pathogenic mosaic mutations...
October 26, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29261000/successful-treatment-using-apatinib-with-or-without-docetaxel-in-heavily-pretreated-advanced-non-squamous-non-small-cell-lung-cancer-a-case-report-and-literature-review
#20
Fengying Wu, Shijia Zhang, Guanghui Gao, Jing Zhao, Shengxiang Ren, Caicun Zhou
Although targeted therapy directed toward driver mutations has produced a significant efficacy benefit for patients with non-small cell lung cancer (NSCLC), many patients do not possess mutations associated with the approved targeted drugs. Angiogenic agents play an important role in the therapeutic strategy for advanced NSCLC. Apatinib is a novel tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2. A phase II clinical trial demonstrated the survival benefit of apatinib monotherapy in advanced NSCLC...
December 20, 2017: Cancer Biology & Therapy
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