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B 6 toxicity

Cristina Grávalos, Alfredo Carrato, María Tobeña, Mercedes Rodriguez-Garrote, Gemma Soler, José Mª Vieitez, Luis Robles, Manuel Valladares-Ayerbes, Eduardo Polo, Mª Luisa Limón, Mª José Safont, Eva Martínez de Castro, Pilar García-Alfonso, Enrique Aranda
INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of maintenance therapy with axitinib versus placebo following induction therapy in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: In this double-blinded, phase II trial, patients with mCRC who had not progressed after 6 to 8 months of first-line chemotherapy were randomized to receive axitinib (5 mg twice a day) (arm A) or placebo (arm B). RESULTS: Forty-nine patients were included: 25 in arm A and 24 in arm B...
February 17, 2018: Clinical Colorectal Cancer
Connor M Pettem, Jennifer M Briens, David M Janz, Lynn P Weber
Selenium (Se) is considered an essential trace element, involved in important physiological and metabolic functions for all vertebrate species. Fish require dietary concentrations of 0.1-0.5 μg Se/g dry mass (d.m.) to maintain normal physiological and selenoprotein function, however concentrations exceeding 3 μg/g d.m. have been shown to cause toxicity. As Se is reported to have a narrow margin between essentiality and toxicity, there is growing concern surrounding the adverse effects of elevated Se exposure caused by anthropogenic activities...
March 8, 2018: Aquatic Toxicology
Charu Aggarwal, Andrew R Haas, Susan Metzger, Laura K Aguilar, Estuardo Aguilar-Cordova, Andrea G Manzanera, Gregoria Gómez-Hernández, Sharyn I Katz, Evan W Alley, Tracey L Evans, Joshua M Bauml, Roger B Cohen, Corey J Langer, Steven M Albelda, Daniel H Sterman
Gene-mediated cytotoxic immunotherapy (GMCI) is an immune strategy implemented through local delivery of an adenovirus-based vector expressing the thymidine kinase gene (aglatimagene besadenovec, AdV-tk) followed by anti-herpetic prodrug valacyclovir. A phase I dose escalation trial of GMCI followed by chemotherapy was conducted in patients with malignant pleural effusion (MPE). AdV-tk was administered intrapleurally (IP) in three cohorts at a dose of 1 × 1012 to 1013 vector particles. Primary endpoint was safety; secondary endpoints included response rate, progression-free survival, and overall survival...
February 21, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
David G Ashbrook, Benjamin Hing, Lindsay T Michalovicz, Kimberly A Kelly, Julie V Miller, Wilfred C de Vega, Diane B Miller, Gordon Broderick, James P O'Callaghan, Patrick O McGowan
BACKGROUND: Gulf War illness (GWI) is an archetypal, medically unexplained, chronic condition characterised by persistent sickness behaviour and neuroimmune and neuroinflammatory components. An estimated 25-32% of the over 900,000 veterans of the 1991 Gulf War fulfil the requirements of a GWI diagnosis. It has been hypothesised that the high physical and psychological stress of combat may have increased vulnerability to irreversible acetylcholinesterase (AChE) inhibitors leading to a priming of the neuroimmune system...
March 17, 2018: Journal of Neuroinflammation
Neil H Segal, Aiwu R He, Toshihiko Doi, Ronald Levy, Shailender Bhatia, Michael J Pishvaian, Rossano Cesari, Ying Chen, Craig B Davis, Bo Huang, Aron D Thall, Ajay K Gopal
Purpose: Utomilumab (PF-05082566) is an agonistic mAb that engages the immune costimulatory molecule 4-1BB/CD137. In this first-in-human, phase I, open-label, multicenter, multiple-dose study (NCT01307267) we evaluated safety, tolerability, pharmacokinetics, preliminary clinical activity, and pharmacodynamics of single-agent utomilumab in patients with advanced malignancies. Experimental Design: Dose escalation was based on a standard 3+3 design for doses of utomilumab from 0.006 to 0.3 mg/kg every 4 weeks and a time-to-event continual reassessment method for utomilumab 0...
March 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
H Lindman, M Andersson, J Ahlgren, E Balslev, A Sverrisdottir, S B Holmberg, N O Bengtsson, E H Jacobsen, A B Jensen, J Hansen, M K Tuxen, L Malmberg, K Villman, H Anderson, B Ejlertsen, J Bergh, C Blomqvist
STUDY AIM: Retrospective studies have demonstrated a worse outcome in breast cancer patients not developing leukopenia during adjuvant chemotherapy. The SBG 2000-1 is the first randomised trial designed to compare individually dosed chemotherapy without G-CSF support based on grade of toxicity to standard-dosed chemotherapy based on body surface area (BSA). METHODS: Patients with early breast cancer were included and received the first cycle of standard FEC (fluorouracil 600 mg/m2 , epirubicin 60 mg/m2 , cyclophosphamide 600 mg/m2 )...
March 13, 2018: European Journal of Cancer
Jacob B Williams, Clara G Buchanan, William G Pitt
Background - Patients undergoing chemotherapy can develop resistance not only to the administered drug, but also to many other unrelated types of drugs, a phenomenon known as multidrug resistance. One of the most common mechanisms of multidrug resistance is an elevated expression of drug efflux pumps. Co-delivery of an efflux pump inhibitor with a chemotherapeutic can increase the killing of multidrug resistant cancer cells. Objective - Our hypothesis was that delivering doxorubicin directly to the cytosol of multidrug resistant cancer cells via a folate-targeted liposome loaded with a perfluoropentane emulsion droplet and doxorubicin (folated eLipoDox), along with the delivery of verapamil to block the efflux pumps will prove to be more effective at killing multidrug resistant cancer cells compared to conventional drug delivery...
March 16, 2018: Pharmaceutical Nanotechnology
Li-Na Zhang, Yongping Song, Delong Liu
The prognosis of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains dismal even at this day and age. With salvage chemotherapy, only 29% (range 18 to 44%) of the patients with R/R ALL can be induced into complete remission (CR), with a median overall survival (OS) of 4 months (range 2-6 months). Blinatumomab and inotuzumab ozogamycin (IO) are immunotherapeutic agents that increased CR to 80% and extended survival to 7.7 months in this high-risk population of patients. In the last few years, chimeric antigen receptor (CAR)--engineered T cells have led to major progress in cancer immunotherapy...
March 15, 2018: Journal of Hematology & Oncology
Satoshi Shibata, Shigeyuki Takamatsu, Kazutaka Yamamoto, Miu Mizuhata, Sayuri Bou, Yoshitaka Sato, Mariko Kawamura, Satoko Asahi, Yuji Tameshige, Yoshikazu Maeda, Makoto Sasaki, Tomoyasu Kumano, Satoshi Kobayashi, Hiroyasu Tamamura, Toshifumi Gabata
We evaluated the effectiveness and toxicity of proton beam therapy (PBT) for hepatocellular carcinomas (HCC) >5 cm without fiducial markers using four-dimensional CT (4D-CT) planning. The subjects were 29 patients treated at our hospital between March 2011 and March 2015. The median total dose was 76 Cobalt Gray Equivalents (CGE) in 20 fractions (range; 66-80.5 CGE in 10-32 fractions). Therapy was delivered with end-expiratory phase gating. An internal target volume (ITV) margin was added through the analysis of respiratory movement with 4D-CT...
March 14, 2018: Cancers
Muneeb U Rehman, Shahzada Mudasir Rashid, Saiema Rasool, Sheeba Shakeel, Bilal Ahmad, Sheikh Bilal Ahmad, Hassan Madkhali, Majid Ahmad Ganaie, Sabiya Majid, Showkat Ahmad Bhat
Development of diabetic nephropathy (DN) is directly linked to oxidative stress and inflammation. In this context, inflammatory and oxidative markers have gained much attention as targets for therapeutic intervention. We studied the effect of zingerone in a streptozotocin/high fat diet (STZ/HFD)-induced type 2 diabetic Wistar rat model. Zingerone also known as vanillyl acetone is a pharmacologically active compound present usually in dry ginger. STZ/HFD caused excessive increase in ROS and inflammation in experimental animals...
March 14, 2018: Archives of Physiology and Biochemistry
Ilzira A Minigalieva, Boris A Katsnelson, Larisa I Privalova, Marina P Sutunkova, Vladimir B Gurvich, Vladimir Y Shur, Ekaterina V Shishkina, Irene E Valamina, Oleg H Makeyev, Vladimir G Panov, Anatoly N Varaksin, Tatiana V Bushueva, Renata R Sakhautdinova, Svetlana V Klinova, Svetlana N Solovyeva, Ekaterina Y Meshtcheryakova
Stable suspensions of metal/metalloid oxide nanoparticles (MeO-NPs) obtained by laser ablation of 99.99% pure elemental aluminum, titanium or silicon under a layer of deionized water were used separately, or in three binary combinations, or in a ternary combination to induce subchronic intoxications in rats. To this end, the MeO-NPs were repeatedly injected intraperitoneally (i.p.) 18 times during 6 weeks before measuring a large number of functional, biochemical, morphological and cytological indices for the organism's status...
March 13, 2018: International Journal of Molecular Sciences
Jawad Bilal, Adam Berlinberg, Sandipan Bhattacharjee, Jaren Trost, Irbaz Bin Riaz, Drew J B Kurtzman
OBJECTIVE: To systematically analyze the efficacy and safety of interleukin (IL)-12/23, IL-17, and selective IL-23 inhibitors in moderate to severe plaque psoriasis. METHODS AND RESULTS: 24 randomized placebo-controlled trials were included. Compared to placebo, risk ratios (RR) of achieving PASI-75 and PGA/IGA 0/1 respectively were 20.20 (95% CI 13.82-29.54, p < 0.00001) and 14.55 (10.42-20.31, p < 0.00001) for ustekinumab 90mg, 13.75 (8.49-22.28, p < 0...
March 13, 2018: Journal of Dermatological Treatment
Vineet Singh, Bhawna Pandey, Surindra Suthar
The increasing availability of antibiotics in wastewater has created a serious threat to non-target organisms in the environment. The aim of this study was to evaluate the potential toxicity of amoxicillin on duckweed Spirodela polyrhiza during a short-term exposure (7 d). The duckweed was exposed to a range of environmentally relevant (0.0001-0.01 mg L-1 ) and high (0.1 and 1 mg L-1 ) concentrations of amoxicillin. Subsequently, biomarkers of toxicity such as growth, pigments (Chl a, Chl b and carotenoids), antioxidative enzyme activity (catalase, CAT; superoxide dismutase, SOD; and ascorbate peroxidases, APX), and biochemical content (protein, lipid and starch) were analysed in their fronds...
March 5, 2018: Chemosphere
Kunal Gupta, Hongyue Wang, Sanjiv B Amin
The aim of this study was to evaluate the effect of intermittent parenteral copper supplementation (IPC) on serum copper status and biochemical and hematological measures of copper toxicity and deficiency in premature infants with parenteral nutrition (PN)-associated cholestasis (PNAC). We performed a prospective nested observational study in premature infants with PNAC who received IPC after the development of PNAC. Infants with chromosomal disorders, TORCH (toxoplasmosis, parvovirus, syphilis, rubella, cytomegalovirus, herpes, human immunodeficiency virus) infection, metabolic disorder, and/or surgical abnormality of the hepatobiliary system were excluded...
March 12, 2018: Nutrition in Clinical Practice
Frank J Simutis, Thomas P Sanderson, Gary D Pilcher, Michael J Graziano
The toxicity of avagacestat, a sulfonamide-based gamma (γ)-secretase inhibitor that was in development as a treatment for Alzheimer's disease, was evaluated in a comprehensive nonclinical toxicology program that included 6-month and 1-year repeat-dose toxicity studies in rats and dogs, respectively. There was a spectrum of mechanism-based changes attributed to inhibition of Notch signaling that regulates the differentiation and proliferation of cells throughout development and in adult tissues. In both rats and dogs, ovarian follicular degeneration and atrophy and a low incidence of granulosa cell hyperplasia and benign granulosa-thecal cell tumors were observed...
February 24, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Katia Pane, Mariavittoria Verrillo, Angela Avitabile, Elio Pizzo, Mario Varcamonti, Anna Zanfardino, Antimo Di Maro, Camilla Rega, Angela Amoresano, Viviana Izzo, Alberto Di Donato, Valeria Cafaro, Eugenio Notomista
Peptides with an N-terminal cysteine residue allow site-specific modification of proteins and peptides and chemical synthesis of proteins. They have been widely used to develop new strategies for imaging, drug discovery, diagnostics and chip technologies. Here we present a method to produce recombinant peptides with an N-terminal cysteine residue as a convenient alternative to chemical synthesis. The method is based on the release of the desired peptide from a recombinant fusion protein by mild acid hydrolysis of an Asp-Cys sequence...
March 12, 2018: Bioconjugate Chemistry
K P Rooney, A B Miah, S A Bhide, M T Guerrero-Urbano, M T Sharabiani, K L Newbold, L Grove, K J Harrington, C M Nutting
BACKGROUND AND PURPOSE: To determine the safety and tolerability of dose-escalation using modestly accelerated IMRT in high-risk locally advanced thyroid cancer requiring post-operative radiotherapy, and to report preliminary data on efficacy. MATERIALS AND METHODS: A sequential Phase I dose-escalation design was used. Dose level one (DL1) received 58.8 Gy/28F to the post-operative bed and 50 Gy/28F to elective nodes. DL2 received 66.6 Gy/30F to the thyroid bed, 60 Gy/30F to post-operative nodal levels and 54 Gy/30F to elective nodal levels...
March 7, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Prashant S Devrukhakar, Shiva Shankar M, Shankar G, Srinivas R
Timolol (TIM) is a potent β-adrenergic blocker, useful in treatment of ocular hypertension or open-angle glaucoma. Development and validation of stability indicating LCMS assay method for TIM was accomplished coherent with ICH guideline. Successful chromatographic separation of TIM with its four degradation products was attained by using gradient elution mode on reverse phase column using ammonium acetate buffer, pH 4.6 as mobile phase A and organic solvent as the mobile phase B. Chromatographic conditions were set such as 1...
February 28, 2018: Journal of Pharmaceutical and Biomedical Analysis
C C Marques, C Santos-Silva, C Rodrigues, J E Matos, T Moura, M C Baptista, A E M Horta, R J B Bessa, S P Alves, G Soveral, R M L N Pereira
The cryopreservation process must be improved to enhance oocyte cryosurvival and functionality. Two protocols with different cryoprotectants (CPAs), containing either ethylene glycol (EG), dimethyl sulfoxide (DMSO) and sucrose (EGDMSO) or 1,2-propanediol and sucrose (PrOH) were evaluated. In both protocols, calcium (Ca2+ ) free or -containing base media were tested. Oocytes were subjected to vitrification or only exposed to CPAs without immersion in liquid nitrogen. Oocyte's viability, cortical granules location and competence for development after fertilization were assessed...
March 7, 2018: Cryobiology
Zhe Liu, Lifeng Xie, Tiequn Bian, Guoan Qi, Zhihong Wang
OBJECTIVE: Infective endocarditis is usually caused by Streptococcus sanguinis and characterized by inflammatory responses in the endocardium. This study aimed to investigate if the new compound (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (TIM) isolated from Alpinia katsumadai Hayata could provide protection against lipoteichoic acid (LTA)-induced cell damage in embryonic rat heart cells (H9c2). METHODS: LTA-induced cell damage was established in H9c2, and the protective effects of TIM against the cell damage were examined at different concentrations (0...
March 2018: Anatolian Journal of Cardiology
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