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https://www.readbyqxmd.com/read/28449393/a-phase-1-study-of-the-c-met-inhibitor-tivantinib-arq197-in-children-with-relapsed-or-refractory-solid-tumors-a-children-s-oncology-group-study-phase-1-and-pilot-consortium-trial-advl1111
#1
James I Geller, John P Perentesis, Xiaowei Liu, Charles G Minard, Rachel A Kudgus, Joel M Reid, Elizabeth Fox, Susan M Blaney, Brenda J Weigel
BACKGROUND: The c-Met receptor tyrosine kinase is dysregulated in many pediatric cancers. Tivantinib is an oral small molecule that inhibits the c-Met receptor tyrosine kinase. A phase 1 and pharmacokinetic (PK) trial evaluating tivantinib was conducted in children with relapsed/refractory solid tumors. METHODS: Oral tivantinib capsules were administered twice daily with food, continuously in 28-day cycles. Dose levels 170, 200, and 240 mg/m(2) /dose were evaluated using a rolling-six design (Part A)...
April 27, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28445949/lmp1-slamf1high-cells-are-associated-with-drug-resistance-in-epstein-barr-virus-positive-farage-cells
#2
Heejei Yoon, Young Hyeh Ko
How Epstein-Barr virus (EBV) affects the clinical outcome of EBV-positive diffuse large B-cell lymphoma (DLBCL) remains largely unknown. The viral oncogene LMP1 is at the crux of tumorigenesis and cell survival. Therefore, we examined the association between LMP1high cells drug resistance. We first assessed SLAMF1 as a surrogate marker for LMP1high cells. LMP1 and its target gene CCL22 were highly expressed in SLAMF1high Farage cells. These cells survived longer following treatment with a combination of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444958/role-of-cytochrome-p450-3a4-and-1a2-phenotyping-in-patients-with-advanced-non-small-cell-lung-cancer-nsclc-receiving-erlotinib-treatment
#3
Zinnia P Parra-Guillen, Peter B Berger, Manuel Haschke, Massimiliano Donzelli, Daria Winogradova, Bogumila Pfister, Martin Früh, Charlotte Kloft, Stephan Krähenbühl, Silke Gillessen, Markus Joerger
Erlotinib is metabolized by cytochrome p450 (CYP) 3A and CYP1A. This study assessed CYP3A4 (midazolam) and CYP1A2 (caffeine) phenotyping in plasma and dried blood spots (DBS) for predicting the pharmacokinetics and toxicity of erlotinib in 36 patients with advanced NSCLC. On day 1, erlotinib 150 mg OD. was initiated, and the 2 oral probe drugs midazolam (2mg) and caffeine (100mg) were added on day 1. Plasma and DBS were collected for erlotinib, OSI-420 and probe drugs for up to 6 hr on day 1 and 2-weekly up to week 10...
April 26, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28444898/an-isoquinolin-1-2h-imine-derivative-induces-cell-death-via-generation-of-reactive-oxygen-species-and-activation-of-jnk-in-human-a549-cancer-cells
#4
Jing Liu, Tongyang Liu, Hanchuan Mou, Shuting Jia, Chao Huang, Shengjiao Yan, Jun Lin, Ying Luo, Jihong Zhang
BACKGROUND: Compound11-benzoyl-10-chloro-7,9-difluoro-6-imino-2,3,4,6-tetrahydro-1H-pyrimido[1,2-b]isoquinoline-8-carbonitrile (HC6h) is a novel polyhalo 1,3-diazaheterocycle fused isoquinolin-1(2H)-imines derivative, which displays good anticancer activity and low toxicity in vivo. However, the underlying anticancer mechanisms have not previously been identified. METHODS: The proliferation of A549 was assessed by MTT assay. The reactive oxygen species (ROS) level was assessed in A549 with a H2 DCFDA probe...
April 26, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28444390/characterisation-of-drug-specific-signalling-between-primary-human-hepatocytes-and-immune-cells
#5
Monday O Ogese, Lee Faulkner, Roz E Jenkins, Neil S French, Ian M Copple, Daniel J Antoine, Mohamed Elmasry, Hasan Malik, Christopher E Goldring, B Kevin Park, Catherine Betts, Dean J Naisbitt
It is now apparent that antigen-specific T-cells are activated in certain patients with drug-induced liver injury (DILI). Since cross-talk between hepatocytes and immune cells is likely to be critical in determining the outcome of drug exposure, the aim of this study was to profile the signals released by drug-treated hepatocytes and to characterise the impact of these molecules on dendritic cells. Human hepatocytes were exposed to three drugs (flucloxacillin, amoxicillin and isoniazid) associated with DILI potentially mediated by the adaptive immune system as drug-specific T-cells have been isolated from DILI patients, and the metabolite nitroso-sulfamethoxazole (SMX-NO)...
April 21, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28443252/open-label-phase-ii-clinical-trial-in-75-patients-with-advanced-hepatocellular-carcinoma-receiving-daily-dose-of-tableted-liver-cancer-vaccine-hepcortespenlisimut-l
#6
Marina G Tarakanovskaya, Jigjidsuren Chinburen, Purev Batchuluun, Chogsom Munkhzaya, Genden Purevsuren, Dorjiin Dandii, Tsogkhuu Hulan, Dandii Oyungerel, Galyna A Kutsyna, Alan A Reid, Vika Borisova, Allen I Bain, Vichai Jirathitikal, Aldar S Bourinbaiar
BACKGROUND: An increasing number of studies is now devoted to immunotherapy of cancer. We evaluated the clinical benefit of hepcortespenlisimut-L (Hepko-V5 [formerly known as V5])-an oral therapeutic vaccine designated by the United States Food and Drug Administration (FDA) as an orphan drug for treatment of hepatocellular carcinoma (HCC). V5 was initially developed by us in 2002 to treat hepatitis B or C viral infections and liver cirrhosis. METHODS: The outcome of open-label Phase II trial of daily dose of V5 pill was analyzed retrospectively...
2017: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/28442756/crystal-structure-based-discovery-of-a-novel-synthesized-parp1-inhibitor-ol-1-with-apoptosis-inducing-mechanisms-in-triple-negative-breast-cancer
#7
Leilei Fu, Shuya Wang, Xuan Wang, Peiqi Wang, Yaxin Zheng, Dahong Yao, Mingrui Guo, Lan Zhang, Liang Ouyang
Poly (ADP-ribose) polymerase-1 (PARP1) is a highly conserved enzyme focused on the self-repair of cellular DNA damage. Until now, numbers of PARP inhibitors have been reported and used for breast cancer therapy in recent years, especially in TNBC. However, developing a new type PARP inhibitor with distinctive skeleton is alternatively promising strategy for TNBC therapy. In this study, based on co-crystallization studies and pharmacophore-docking-based virtual screening, we discovered a series of dihydrodibenzo[b,e]-oxepin compounds as PARP1 inhibitors...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28442242/dosimetric-analysis-of-liver-toxicity-after-liver-metastasis-stereotactic-body-radiation-therapy
#8
Aisling Barry, Andrew McPartlin, Patricia Lindsay, Lisa Wang, James Brierley, John Kim, Jolie Ringash, Rebecca Wong, Rob Dinniwell, Tim Craig, Laura A Dawson
PURPOSE: The aim of this study is to describe the incidence and type of liver toxicity seen following liver metastases stereotactic body radiation therapy (SBRT) and the corresponding clinical and dosimetric factors associated with toxicity. METHODS AND MATERIALS: Between 2002 and 2009, 81 evaluable patients with liver metastases were treated on 2 prospective studies assessing SBRT, with prescription doses based on the effective liver volume irradiated evaluated...
March 9, 2017: Practical Radiation Oncology
https://www.readbyqxmd.com/read/28441764/altered-adipogenesis-in-zebrafish-larvae-following-high-fat-diet-and-chemical-exposure-is-visualised-by-stimulated-raman-scattering-microscopy
#9
Marjo J den Broeder, Miriam J B Moester, Jorke H Kamstra, Peter H Cenijn, Valentina Davidoiu, Leonie M Kamminga, Freek Ariese, Johannes F de Boer, Juliette Legler
Early life stage exposure to environmental chemicals may play a role in obesity by altering adipogenesis; however, robust in vivo methods to quantify these effects are lacking. The goal of this study was to analyze the effects of developmental exposure to chemicals on adipogenesis in the zebrafish (Danio rerio). We used label-free Stimulated Raman Scattering (SRS) microscopy for the first time to image zebrafish adipogenesis at 15 days post fertilization (dpf) and compared standard feed conditions (StF) to a high fat diet (HFD) or high glucose diet (HGD)...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28438492/metabolism-of-14-c-octamethylcyclotetrasiloxane-14-c-d4-or-14-c-decamethylcyclopentasiloxane-14-c-d5-orally-gavaged-in-rainbow-trout-oncorhynchus-mykiss
#10
Jeanne Y Domoradzki, Jacob M Sushynski, Lisa M Thackery, Timothy A Springer, Timothy L Ross, Kent B Woodburn, Jeremy A Durham, Debra A McNett
Critical factors (uptake, distribution, metabolism and elimination) for understanding the bioaccumulation/biomagnification potential of Octamethylcyclotetrasiloxane (D4) and Decamethylcyclopentasiloxane (D5) siloxanes in fish were investigated to address whether these chemicals meet the "B" criteria of the Persistent, Bioaccumulative, and Toxic (PBT) classification. A metabolism study was conducted in rainbow trout whereby a 15mg [(14)C]D4 /kg bw or [(14)C]D5/kg bw as a single bolus oral dose was administered via gavage...
April 21, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28436085/effect-of-triclosan-on-anuran-development-and-growth-in-a-larval-amphibian-growth-and-development-assay
#11
Douglas J Fort, Michael B Mathis, Sascha Pawlowski, Jeffrey C Wolf, Robert Peter, Samantha Champ
A larval amphibian growth and development assay was performed to evaluate the potential effects of environmentally-relevant concentrations of triclosan (TCS) on amphibian development and growth. Xenopus laevis were exposed to TCS 0.0 (control), 6.3, 12.5 and 25.0 μg l(-1) (estimated maximum tolerable concentration) until 10 weeks post-metamorphosis. At median metamorphosis time (Nieuwkoop and Faber stage 62), five larvae per replicate were collected for snout-vent length, hind limb length and body weight measurements, and histopathological examination of thyroid glands...
April 24, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28434799/improved-outcomes-with-dose-escalation-in-localized-prostate-cancer-treated-with-precision-image-guided-radiotherapy
#12
Hamid Raziee, Fabio Y Moraes, Jure Murgic, Melvin L K Chua, Melania Pintilie, Peter Chung, Cynthia Ménard, Andrew Bayley, Mary Gospodarowicz, Padraig Warde, Tim Craig, Charles Catton, Robert G Bristow, David A Jaffray, Alejandro Berlin
BACKGROUND AND PURPOSE: Dose-escalated radiotherapy (DE) improves outcomes in localized prostate cancer (PCa). The impact of DE in the context of image-guided radiotherapy (IGRT) remains unknown. Herein, we determined outcomes of three sequential cohorts treated with progressive DE-IGRT. MATERIALS AND METHODS: We analyzed data from 1998 to 2012. Patients treated with radical radiotherapy were included, with three sequential institutional schedules: (A) 75.6Gy, (B) 79...
April 20, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28434633/echocardiographic-evaluation-of-left-ventricular-mass-index-in-children-with-hypospadias-after-hormonal-stimulation-with-topical-testosterone-a-randomized-controlled-trial
#13
Elisabeth Campos de Andrade, Kelly Christina de Castro Paiva, Sarah da Silva Guedes, Mariana Lima C Souza, Marina Novellino Pereira, Laura Pimenta Miana, André Avarese de Figueiredo, José de Bessa, José Murillo B Netto
INTRODUCTION: Testosterone is often used in the preoperative period of hypospadias surgery. Previous studies have demonstrated the presence of androgen receptors in cardiac myocytes that can modulate the phenotype. The use of supraphysiological doses of androgens can lead to toxicity on the heart muscle and, in some cases, to left ventricular hypertrophy. This randomized double blind controlled clinical trial aims to evaluate the effect of topical testosterone on left ventricular mass index in boys with hypospadias...
April 10, 2017: Journal of Pediatric Urology
https://www.readbyqxmd.com/read/28434191/the-effect-of-parotid-gland-sparing-imrt-on-salivary-composition-flow-rate-and-xerostomia-measures
#14
Thomas M Richards, Tara Hurley, Lorna Grove, Kevin J Harrington, Guy H Carpenter, Gordon B Proctor, Christopher M Nutting
OBJECTIVES: To describe parotid gland (PG) saliva organic and inorganic composition and flow rate changes, after curative intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC) and analyse the relationship between PG saliva analytes and xerostomia measures. METHODS AND MATERIALS: Twenty-six patients recruited to five prospective phase 2 or 3 trials which assessed toxicity and efficacy of IMRT by HNC subsite, provided longitudinal PG salivas. Salivary flow rate, subjective and objective xerostomia measures were prospectively collected and salivas tested for inorganic and organic analytes...
April 23, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28433833/in-vitro-antitumor-activity-metal-uptake-and-reactivity-with-ascorbic-acid-and-bsa-of-some-gold-iii-complexes-with-n-n-ethylenediamine-bidentate-ester-ligands
#15
Nebojša Pantelić, Bojana B Zmejkovski, Branka Kolundžija, Marija Đorđić Crnogorac, Jelena M Vujić, Biljana Dojčinović, Srećko R Trifunović, Tatjana P Stanojković, Tibor J Sabo, Goran N Kaluđerović
Four novel gold(III) complexes of general formulae [AuCl2{(S,S)-R2eddl}]PF6 (R2eddl=O,O'-dialkyl-(S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoate, R=n-Pr, n-Bu, n-Pe, i-Bu; 1-4, respectively), were synthesized and characterized by elemental analysis, UV/Vis, IR, and NMR spectroscopy, as well as high resolution mass spectrometry. Density functional theory calculations pointed out that (R,R)-N,N'-configuration diastereoisomers were energetically the most favorable. Duo to high cytotoxic activity complex 3 was chosen for stability study in DMSO, no decomposition occurs within 24h, and for the reaction with ascorbic acid in which was reduced immediately...
April 4, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28432965/spatiotemporal-description-of-btex-volatile-organic-compounds-in-a-middle-eastern-megacity-tehran-study-of-exposure-prediction-for-environmental-health-research-tehran-sepehr
#16
Heresh Amini, Vahid Hosseini, Christian Schindler, Hossein Hassankhany, Masud Yunesian, Sarah B Henderson, Nino Künzli
The spatiotemporal variability of ambient volatile organic compounds (VOCs) in Tehran, Iran, is not well understood. Here we present the design, methods, and results of the Tehran Study of Exposure Prediction for Environmental Health Research (Tehran SEPEHR) on ambient concentrations of benzene, toluene, ethylbenzene, p-xylene, m-xylene, o-xylene (BTEX), and total BTEX. To date, this is the largest study of its kind in a low- and middle-income country and one of the largest globally. We measured BTEX concentrations at five reference sites and 174 distributed sites identified by a cluster analytic method...
April 19, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28430649/abcg2-and-ncf4-polymorphisms-are-associated-with-clinical-outcomes-in-diffuse-large-b-cell-lymphoma-patients-treated-with-r-chop
#17
Duo Liu, Nan Wu, Haiming Sun, Mei Dong, Tianzhu Guo, Peng Chi, Guofu Li, Donglin Sun, Yan Jin
The impact of pharmacogenetics on predicting survival in diffuse large B-cell lymphoma (DLBCL) remains unclear. We tested 337 DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 9 single nucleotide polymorphisms from 6 genes (CD20, FCGR2A, NAD(P)H, ABCC2, ABCG2 and CYP3A5). Patients who carried the NCF4 rs1883112 GG genotype showed significantly shorter progression-free survival (PFS) (P = 0.023) and event-free survival (EFS) (P < 0.001) comparing with A allele...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428282/whither-radioimmunotherapy-to-be-or-not-to-be
#18
Damian J Green, Oliver W Press
Therapy of cancer with radiolabeled monoclonal antibodies has produced impressive results in preclinical experiments and in clinical trials conducted in radiosensitive malignancies, particularly B-cell lymphomas. Two "first-generation," directly radiolabeled anti-CD20 antibodies, (131)iodine-tositumomab and (90)yttrium-ibritumomab tiuxetan, were FDA-approved more than a decade ago but have been little utilized because of a variety of medical, financial, and logistic obstacles. Newer technologies employing multistep "pretargeting" methods, particularly those utilizing bispecific antibodies, have greatly enhanced the therapeutic efficacy of radioimmunotherapy and diminished its toxicities...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28425451/ifn%C3%AE-protects-neurons-from-damage-in-a-murine-model-of-hiv-1-associated-brain-injury
#19
Victoria E Thaney, Alan M O'Neill, Melanie M Hoefer, Ricky Maung, Ana B Sanchez, Marcus Kaul
Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424325/fda-approval-summary-atezolizumab-for-the-treatment-of-patients-with-progressive-advanced-urothelial-carcinoma-after-platinum-containing-chemotherapy
#20
Yang-Min Ning, Daniel Suzman, V Ellen Maher, Lijun Zhang, Shenghui Tang, Tiffany Ricks, Todd Palmby, Wentao Fu, Qi Liu, Kirsten B Goldberg, Geoffrey Kim, Richard Pazdur
Until recently in the United States, no products were approved for second-line treatment of advanced urothelial carcinoma. On May 18, 2016, the U.S. Food and Drug Administration approved atezolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Atezolizumab is a programmed death-ligand 1 (PD-L1) blocking antibody and represents the first approved product directed against PD-L1...
April 19, 2017: Oncologist
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